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solar elastosis refers to histopathologic changes in degenerative dermal elastic tissue that occurs in photodamaged skin . the predominant histological feature of solar elastosis is basophilic degeneration of elastotic fibers in the dermis , separated from the epidermis by a narrow band of normal - appearing collagen ( grenz zone ) with collagen fibers arranged horizontally . the degree of elastosis correlates with the cumulative amount of ultraviolet radiation to which the skin has been exposed . these are distinguished by a combination of anatomic location , clinical appearance , and histopathologic findings . otherwise , the other clinical patterns which are histologically similar are usually grouped together under the term solar elastosis . solar elastotic syndromes include solar elastosis , favre - racouchot syndrome , elastotic nodules of the ears , collagenous and elastotic plaques of the hands and colloid milia [ 4 , 5 , 6 , 7 , 8 , 9 , 10 ] . here we present two patients with a rare clinical presentation of solar elastosis in the papular form . a 55-year - old chinese man was referred to our clinic for regular screening for skin cancer . he had a history of diabetes mellitus , hypertension and had received a kidney transplant more than 10 years ago . physical examination revealed three similar pearly telangiectatic red - brown firm papules on the nose and right nasal philtrum ( fig . the lesions were asymptomatic and had been present for 2 months . a 3-mm punch biopsy of a representative lesion was performed . histological evaluation of the skin showed marked solar elastosis with non - specific patchy chronic lymphoplasmacytic infiltrate ( fig . 2 ) . there was no evidence of malignancy on examination of multiple sections of tissue . a 75-year - old chinese man , on regular follow - up for psoriasis , presented with a 1-month history of a bump on the face which bled a little with scratching . moreover , he had a history of ischemic heart disease , hypertension , hyperlipidemia , diabetes mellitus and hypoadrenalism secondary to exogenous steroid use in the past . physical examination revealed a 3-mm skin - colored papule on the left philtrum ( fig . there was mild epidermal acanthosis with no evidence of tumor on examination of multiple tissue sections . it appears to be uncommon for solar elastosis to manifest in a papular form and very often , it can resemble other skin disorders . some of the mimics of papular solar elastosis include basal cell carcinoma , sebaceous hyperplasia , molluscum contagiosum and actinic keratosis . he described the skin lesions as asymptomatic , shiny , smooth , firm papules , 110 mm in diameter , that can be multiple or solitary , with various colorations . he reported two cases of papular elastosis and since then there has been no other literature found with regards to this unique presentation of solar elastosis . it presents as thick , dry , coarsely wrinkled skin with loss of skin tone . one of the most well recognized clinical variant is cutis rhomboidalis nuchae , in which there is thickened yellow leathery - appearing skin at the posterolateral aspect of the neck . the origin of the elastotic material in the dermis has been postulated to be due to degradation of collagen and/or elastic fibers , overactive sun - damaged fibroblast synthesizing new elastic tissue , and an abnormal synthetic and degradative process . in favre - rachouchot syndrome , thickened yellow plaques with follicular cysts surrounded by multiple open comedones are typical . the skin around the eyes is a usual site , and the condition occurs more commonly in older men . histological examination shows increased elastic tissue with thickened , tortuous fibers in the upper and mid dermis . elastotic nodule(s ) of the ear is characterized by single or multiple bilateral , firm to hard pale nodules on the antihelix or helix . histological features include irregular coarse , elastotic material and clumped masses of thick fibers on a background of marked solar elastosis . clinically , they may resemble basal cell carcinoma , amyloidosis , gouty tophi and chondrodermatitis nodularis helicis . collagenous and elastotic plaques of the hands is a slowly progressive condition more often found in older men with waxy linear plaques at the junction of the dorsal and palmar skin on the hand . histological examination shows amorphous basophilic elastotic masses and thickened , fragmented , calcified elastic fibers in the upper and mid dermis . the thick collagen bundles have a haphazard arrangement , but with a proportion running perpendicular to the surface . adult colloid milium , another solar elastotic dermatosis , is the closest clinical differential diagnosis of papular elastosis . light microscopy shows accumulation of a homogenous , amorphous faintly eosinophilic material with cleft - like spaces in the upper and mid dermis . the cause for the colloid deposition in the dermis is still uncertain , but some authors have suggested that it is from degeneration of collagen and/or elastic fibers due to actinic action . there is also a possibility that this elastotic material is newly formed from sun - damaged fibroblast . interestingly , both our patients were on immunosuppressive therapy and they both had dual agents . there is strong evidence that organ transplant recipients on immunosuppressive therapy have an increased risk of actinic damage and skin cancers [ 12 , 13 , 14 ] . it has also been reported that transplant recipients with a history of skin cancer may experience a deceleration of cutaneous carcinogenesis after stopping immunosuppressants . further research work is needed to elucidate the molecular mechanisms of immunosuppression leading to an acceleration of solar elastosis . in summary , we have presented two cases of papular elastosis that occurs in chronically sun - damaged skin . it is necessary to obtain biopsy confirmation as this condition is very rare , and important differential diagnoses such as basal cell carcinoma need to be ruled out . the most effective strategy to manage solar elastosis is prevention of actinic - related damage with sun avoidance , protective clothing and sunscreen .

solar elastosis is a degenerative condition of elastic tissue in the dermis due to prolonged sun exposure . there are a variety of clinical manifestations of solar elastosis . in its most common form , solar elastosis manifests as yellow , thickened , coarsely wrinkled skin . we report two uncommon cases of severe solar elastosis with a papular morphology . its presentation can closely mimic a host of cutaneous disorders and thus , although it is helpful to be cognizant of this entity , it is still crucial to biopsy these lesions to avoid missing a more sinister condition .

tattoos are produced by introducing colorants of various compositions into the skin , either accidentally or for cosmetic purposes . a 62-year - old male presented with a cosmetic tattoo and requested a total excision of the lesion . dermatopathologic analysis of the excised tissue with hematoxylin and eosin examination , as well as immunohistochemistry was performed . h&e staining demonstrated classic histologic features of a tattoo . utilizing immunohistochemistry , dermal histiocytic antigen presenting cells stained with ham56 and cd68 antibodies ; the staining was present surrounding the tattoo pigment . we identified two macrophage markers ( ham56 and cd68 ) surrounding dermal tattoo pigment . a minimal dermal inflammatory immune we suggest that tattoo materials and techniques could be utilized in therapeutic delivery for diseases such recessive dystrophic epidermolysis bullosa , potentially preventing immune rejection of gene therapy agents . cosmetic tattoo ink is the substance injected into the dermis in the creation of a cosmetic tattoo . there are multiple types of tattoos : amateur , professional , cosmetic , medicinal , and traumatic[13 ] . in cosmetic tattoos , the specific ingredients of the colorants are not well regulated , and not subjected to pharmacological and toxicological testing[13 ] . pigments that are utilized in tattoo inks include minerals , vegetable dyes , plastics , and metallic salts[13 ] . the most common tattoo pigments include carmine , indigo , vermilion , india ink , chromium green , cobalt blue , cinnabar , cadmium sulfide , and manganese[13 ] . representative tattoo colors and a correlating pigment include : blue , calcium copper silicate ; red , iron oxide ; green , chromium oxide ; yellow , curcuma ; black , carbon , and white , zinc oxide[13 ] some of the frequently used liquid carriers include : listerine , witch hazel , purified water , propylene glycol , vodka and glycerine[13 ] . a 62-year - old male presented for a cosmetic removal of a black tattoo , present for more than twenty years . after a surgical removal of the tattoo , the tissue was sent for dermatopathologic analysis for hematoxylin and eosin ( h & e ) analysis . our macrophage ham56 mouse monoclonal antibody was obtained from genway biotech , inc.(san diego , california , usa ) . we also tested for monoclonal mouse anti - human cd68 ( dako , carpinteria , california , usa ) examination of the h & e tissue sections demonstrated a histologically unremarkable epidermis . in addition , dark , granular pigment deposition was observed in focal areas of the dermis . in many areas , next , ihc staining demonstrated positive staining with ham56 and cd68 , both highlighting cells engulfing the pigment in these areas of the dermis ( figure 1 ) . a. h & e sections demonstrate dark , granular tattoo pigment in the dermis ( red arrow , 400x ) . b , c and d note positive ihc staining with ham56 antibody ( red / brown staining ; blue arrows at 400 , 200 and 100x , respectively ) . e. ihc cd68 staining near upper and intermediate dermal blood vessels ( brown staining ; red arrows , 40x ) . f. ihc cd68 staining near blood vessels around dermal pilosebaceous units ( brown staining ; red arrows , 100x ) . g ihc ham56 positive staining on histiocytic foreign body type giant cells ( brown staining ; red arrow ) ( 400x and 100x , respectively ) . i. h & e staining again shows deposits of tattoo materials , concentrated around the blood vessels ( red arrows , 100x ) . tattoo inks are meant to establish permanent skin color changes ; however , the color made fade over time due to the immune system recognizing the tattoo as a foreign body . however , most of the pigment molecules are too large for immune system cells to destroy ; thus , the coloring remains . the most common reactions to tattoos are 1 ) photosensitivity , 2 ) formation of granulomatous reactions(including in a few cases sarcoidoial lesions ) , 3 ) milium cysts , and 4 ) hypersensitivity reactions to any of the tattoo components . although some modern tattoo inks are advertised to be 100% safe , these reactions may occur with their usage . the plastic - based pigments have been reported to be involved in multiple adverse reactions . nuclear magnetic resonance and mass spectroscopy can help to determine the specific substances within a tattoo ; in our case , these tests were not performed . after reviewing of the literature , we found minimal information regarding the immune response to tattoos . in our case , we document the presence of ham56 and cd68 cell populations responding to the tattoo ; both of these markers highlight active antigen presenting cells . the cd68 protein gene encodes a 110-kd transmembrane glycoprotein that is highly expressed by human monocytes and tissue macrophages[68 ] . the cd68 protein is a member of the lysosomal / endosomal - associated membrane glycoprotein family[68 ] . scavenger receptors typically function to clear cellular debris , promote phagocytosis and mediate the recruitment and activation of macrophages . ham56 labels human tissue macrophages , germinal center tangible body macrophages , interdigitating histiocytes of lymph nodes , kupffer cells of the liver and alveolar macrophages within the lung[68 ] . the anti - ham56 antibody reacts with monocytes , but is not reactive with b or t lineage lymphocytes[68 ] . extended studies on tattoos may provide a better understanding of how the immune system interfaces with tattoo components . such a modified gun would utilize no ink ; rather , it would contain a vibrating solid needle and insert implants of dna fragments or other substances under the skin , utilizing tattoo components as delivery vehicles . we suggest that delivery of gene therapy via such a system could advance the efficacy of the therapy , vis - - vis prevention of interference from the immune system via the non - immunologic , or

contexttattoos are produced by introducing colorants of various compositions into the skin , either accidentally or for cosmetic purposes.case report : a 62-year - old male presented with a cosmetic tattoo and requested a total excision of the lesion . dermatopathologic analysis of the excised tissue with hematoxylin and eosin examination , as well as immunohistochemistry was performed . h&e staining demonstrated classic histologic features of a tattoo . utilizing immunohistochemistry , dermal histiocytic antigen presenting cells stained with ham56 and cd68 antibodies ; the staining was present surrounding the tattoo pigment.conclusionswe identified two macrophage markers ( ham56 and cd68 ) surrounding dermal tattoo pigment . a minimal dermal inflammatory immune was noted to the tattoo pigment . moreover , the immune response and/or tolerance to tattoos is not well characterized . we suggest that tattoo materials and techniques could be utilized in therapeutic delivery for diseases such recessive dystrophic epidermolysis bullosa , potentially preventing immune rejection of gene therapy agents .

abdominal tuberculosis ( tb ) is not uncommon in the developing world , but isolated colonic tb is rare ; it has been estimated that 2 - 3% of patients with abdominal tb have isolated colonic involvement ( 1 ) . it also accounts for 10.8% of all gastrointestinal tb with the commonest affected site being the transverse colon , followed by rectum and ascending colon ( 2 ) . it commonly presents with vague abdominal pain , fever , weight loss , diarrhea and abdominal mass . in more than two thirds of affected patients a 40-year - old male presented with 6-month history of vague right - sided abdominal pain , diarrhoea , and weight loss . he was apyrexial with a palpable mobile mass in the right hypochondrium which was non - tender and measured 7x5 cm . his chest x - ray was normal , but computed tomography ( ct ) scan of the abdomen revealed a large polypoid mass lesion in the right colon extending from the ileo - caecal valve with lumen - narrowing and mildly enlarged pericolic lymph nodes . a provisional diagnosis of right colonic cancer was made and he was prepared for right hemicolectomy . cut section shows polypoidal growth arising from the ascending colon on laparotomy , the mass in the subhepatic area was recognized with minimal free straw - colour peritoneal fluid . hence , a right hemicolectomy was performed with an ileo - transverse anastomosis , and the specimen was sent for gross examination and histopathology ( figure 1 and figure 2 ) . he was started on anti - tuberculous therapy consisting of daily doses of isoniazid 300 mg , rifampicin 600 mg and ethambutol 900 mg for two months , followed by four months of isoniazid and rifampicin therapy ; the whole treatment lasted six months . the patient made a complete recovery without complications and is currently on regular follow - up . the incidence of colon tb is increasing with the rise in numbers of high risk patients such as hiv - infected individuals , patients with chronic renal disease , and immunosuppressed patients on immunosuppressive or prolonged steroid therapy . most reported colonic tb cases in non - immunosuppressed individuals come from the indian subcontinent ( 1 - 3 ) . the most common presenting symptom and abnormal physical sign are abdominal pain and abdominal mass ( 90% and 58% of patients , respectively ) ( 4 ) . varied and nonspecific presenting symptoms make early diagnosis difficult and elusive with subsequent delays in management . to avoid such a dangerous delay in management , some authors recommend a trial of anti - tuberculous chemotherapy in patients with high clinical suspicion on the basis of colonoscopic appearance alone , even in the absence of the classic features of tb , after ruling out other causes , especially cancer and crohn s disease by histopathological examination ( 1,3 ) . this coexistence may be of high frequency necessitating the need for epidemiological and histopathological investigations into the aetiological relationship between the two diseases ( 6 ) . colonoscopic examination with combined histopathologic and bacteriologic study of biopsy specimens is a powerful tool for the diagnosis of intestinal tb in 60% of patients without the need for resectional surgery ( 1 ) . however , the colonoscopic features are quite variable , but typically are those of circumferential ulceration or a single ulcer with an elevated or nodular margin surrounded by hyperemic mucosa ( 3 ) . other colonoscopic features include nodules , deformed segment of the colon , polypoid lesions or pseudopolyps , strictures , and less commonly , fibrous bands forming mucosal bridges ( 3 ) . like in this case , tuberculous lesions may mimic carcinoma in 20% of cases and acid - fast bacilli ( afb ) may not be isolated at all ( 4 ) . nevertheless , polymerase chain reaction ( pcr ) analysis of a colonic biopsy may reveal afb of the mycobacterium tuberculosis species . it is a rapid , sensitive , and specific method in the diagnosis of intestinal tb . it is also valuable in the differentiation between intestinal tb and crohn 's disease ( 7 ) . such features are cecal amputation , ileocecal thickening and inflammation , shortening of the ascending colon , gaping of the ileocecal valve , mesenteric adenopathy , a misty mesentery , diffuse omental infiltration , loculated high - density ascites , an enhancing peritoneum with or without an omental line , nodularity of the surface of the mesenteric leaves , and transperitoneal permeation ( 8) . other commonly observed radiological findings include strictures ( 54% ) , colitis ( 39% ) and less frequently polypoid lesions ( 7% ) ( 8) . complications noted were in the form of perforations and fistulae in less than 20% of cases ( 2 ) . this case highlights the ease with which colonic tb may be mistaken for colonic cancer and the dilemma of diagnosing it radiologically and endoscopically . the clinical features of both these conditions are identical and , occasionally , only histopathology may provide the final diagnosis .

isolated colonic tuberculosis ( tb ) is rare , and the symptoms are nonspecific making early diagnosis and management difficult . although colonoscopy and biopsy is an important diagnostic modality , the features are variable and the distinction from other conditions of the colon , especially crohn s disease and cancer , may be impossible without surgical resection . we report a case of ascending colon tb which was mistaken for colonic cancer during colonoscopy , with non - specific results on biopsy . the diagnosis was finally made when the histopathology report was received . the diagnostic dilemma of colonic tb is discussed .

cytomegalovirus ( cmv ) infection of the gastrointestinal tract is one of the more uncommon opportunistic infections in aids . the incidence of cmv infection and complications in people already afflicted with cmv has dropped precipitously after the advent of highly active antiretroviral therapy ( haart ) [ 2 , 3 , 4 ] . patients who are either not on haart or are non - compliant with it present with varied and often serious manifestations of cmv infection . these manifestations include esophagitis which usually presents as multiple ulcers in the lower part , though an uncommon diffuse variant has been described ; gastritis which usually presents with epigastric discomfort and rarely massive hemorrhage ; enteritis with pain and diarrhea and colitis with pain , diarrhea and rarely lower gastrointestinal bleeding . once the diagnosis of cmv infection of the gastrointestinal tract has been made , established treatment protocols including ganciclovir or foscarnet can be started . there have been concerning trends , however , with antiviral resistance pattern of cmv to these antiviral agents , either with conventional regimens or salvage regimens , which would force the clinician to adopt more toxic alternatives such as concurrent ganciclovir - foscarnet regimen , foscavir or cidofovir . apart from their toxicity , the use of these regimens is often curtailed by factors such as poor oral bioavailability , drug resistance on prolonged use and limited efficacy . therefore , a ul97 phosphotransferase mutation in cmv does not usually confer resistance to foscarnet as it does to ganciclovir [ 11 , 12 ] . foscarnet resistance in cmv develops after prolonged treatment for cmv retinitis often via mutations in the viral dna polymerase gene . this new drug - resistant strain of cmv can produce florid manifestations elsewhere as demonstrated in the patient we report below . a 52-year - old hispanic man with hiv - aids , non - complaint with haart , had multiple aids - related opportunistic infections such as three prior episodes of esophageal candidiasis ( confirmed with prior esophagogastroduodenoscopy , egd ) and cmv retinitis on prolonged therapy with foscarnet ( 2 months ) , hepatitis c and latent syphilis . he presented with progressively worsening dysphagia and failure to thrive with electrolyte abnormalities including severe hypokalemia ( 1.7 mg / dl ) and hypophosphatemia ( 2.2 mg / dl ) . foscarnet therapy for cmv retinitis was stopped due to his impaired renal function but was later restarted during his hospital stay . the patient underwent egd on day 7 of hospitalization that revealed diffuse friable mucosa in the upper third of the esophagus and a stricture 25 cm from the upper end of the esophagus but no evidence of candidiasis ( fig . further plans of repeat egd with bougie dilatation were aborted due to high risk of rupture of the esophagus . the esophagogram revealed a large ulceration at the junction of the upper and middle third of the esophagus with associated fusiform stricture ( fig . biopsy samples taken from the area of stricture revealed intranuclear inclusions consistent with cmv esophagitis . meanwhile the patient refused to undergo gastrostomy feeding tube placement while tolerating chopped diet better and was discharged back to his nursing home . this patient was severely immunocompromised and presented with dysphagia secondary to a benign - looking stricture diagnosed with egd . the differential diagnoses of the egd findings in this patient included hiv - related benign esophageal strictures secondary to idiopathic esophageal ulceration , herpetic esophagitis and cmv esophagitis . benign esophageal ulcerations are unlikely in a setting of non - compliance with haart and florid opportunistic infections elsewhere such as cmv retinitis . herpetic ulcers usually present as well - circumscribed volcano - like lesions which distinguish them from usual longitudinal and deeper ulcers seen in cmv infection . the egd findings were more suggestive of cmv being the etiological agent especially in the setting of concomitant cmv retinitis . however the patient had already been on of foscarnet therapy for 2 months prior to this presentation , highlighting the possible paradoxical presentation of a resistant strain of cmv in patients on chronic foscarnet therapy . despite the extensive and deep nature of cmv ulceration in such cases of esophagitis , it has often been noted that there is resolution of cmv esophagitis with initiation of haart and anti - cmv agents such as ganciclovir and foscarnet . such strictures resulting from fibrous healing usually respond well to repeated esophageal dilatations , unlike in this patient in whom bougie dilatation of the cmv stricture was unsuccessful . this case is unusual at several levels , including the facts that the patient had cmv esophagitis with stricturing while on foscarnet and that the stricture was not amenable to bougie dilatation . an increase in the resistance of cmv to conventional first - line anti - cmv agents such as ganciclovir or foscarnet has been reported , but that should not dissuade clinicians from using them for treating primary cmv infection . the secondary resistant cmv infection can be treated with one of the following strategies : sequential therapy with ganciclovir followed by foscarnet ( upon failure of ganciclovir ) or sequential therapy with foscarnet followed by ganciclovir or concurrent combination therapy with both foscarnet and ganciclovir [ 9 , 15 ] , with limited efficacy . it is therefore imperative that physicians be aware of more malignant presentation of cmv while patients are still on chronic conventional anti - cmv therapy and that they consider it among differential diagnoses .

we report the case of a 52-year - old man with hiv - aids , non - complaint with highly active antiretroviral therapy , who presented with long - standing dysphagia . he was treated for three episodes of severe candida esophagitis with fluconazole and later caspofungin due to poor response . in spite of the prolonged treatment courses the patient did not report an improvement in his symptoms . he was also concomitantly being treated for other opportunistic infections including cytomegalovirus ( cmv ) retinitis with i.v . foscarnet for almost 2 months prior to the index presentation . upper esophagogastroduodenoscopy revealed multiple superficial ulcers with stricturing . bougie dilatation was attempted but failed . the biopsy specimens revealed multiple intracellular inclusion bodies pathognomonic of cmv infection . we aim to highlight the increasing resistance of cmv to conventional first - line antiviral agents such as foscarnet .

a 53 years - old male visited to our clinic because of cognitive impairment for two years ago . the patient graduated from university , had worked as an office worker and recently retired . his wife described that , the patient s memory and ability of judgment had been impaired for 2 years , and his verbal output had been decreased . the patient was not taking any medicines previously . because of forgetting his medication schedule , he attached his medicine on his calendar . although he had never lost his ways , he had trouble with driving and made some car accidents because of misperception . he had turned much introversive instead of sociable previously , and showed indifference towards household matters or works related with their offspring . inappropriate laughing was observed in serious situations . without a caregiver , he could not care of his own hygiene or eating . on the first visit , there was no remarkable finding in examination of motor and cerebellar function . the results were interpreted using 1.0 standard deviation ( 16 percentile ) of normal korean population aged 55 , as a cut - off value . he showed time disorientation , and impairments in encoding , retention and retrieval of verbal memory , and retrieval of visual memory . considering the progressive decline in intellectual function affecting memory and other cognitive domain , and interference of activities of daily , he was diagnosed with dementia . at the time , the patient was regarded as early frontotemporal dementia . six months later , he complained about gait disturbance with a feeling of right leg dragging . in addition , he had suffered from the postural imbalance , and difficulties in swallowing and articulation . he developed the orthostatic dizziness and urinary difficulties , including frequency , nocturia and residual urine sense , had also developed . on neurological examination , he was alert . deep tendon reflexes were increased in all extremities , hoffman s signs were positive , bilaterally . gene tests for spinocerebellar ataxia type 1 , 2 , 3 , 6 , 7 , and 17 , and dentatorubropallidoluysian atrophy were all negative . the head up tilt test revealed orthostatic hypotension ; systolic blood pressure was decreased 31 mm hg 3 minutes after standing . verbal and visual memories and frontal lobe functions , including inhibitory function and semantic word fluency , were significantly deteriorated compared with previous test 6 months ago ( table 1 ) . the follow - up brain mri has showed newly developed atrophy of cerebellum , pons and middle cerebellar peduncle ( figure 1 ) . positron emission tomography ( pet ) was performed using f - fluorodeoxyglucose ( fdg ) , and showed decreased cerebral glucose metabolism on the bilateral bagal ganglia , cerebellum , both parietal lobes , and left posterior cingulate gyrus in visual analysis ( figure 2 ) . finally , based on the features of cerebellar ataxia , autonomic dysfunction and pyramidal dysfunction , he was diagnosed with msa - cerebellar type ( msa - c).2 he was prescribed with rivastig - mine for dementia and other medications for urinary problems . this patient had shown rapid progressions of memory impairment , behavioral changes and impairment in executive functions , and been diagnosed with dementia initially . thereafter , cerebellar ataxia with dysautonomia and pyramidal dysfunction had occurred , and finally he was diagnosed with msa - c . msa is a neuro - degenerative disease , which usually occurs sporadically in adults , older than 30 years.2 typically it is presented with parkinsonism , cerebellar ataxia , dysautonomia and pyramidal dysfunction . pathologically , neuronal cell loss , gliosis and syn - immunopositive gci are observed in structures of striato - nigral pathway and olivo - ponto - cerebellar pathway . according to the second consensus statement on the diagnosis of msa,2 msa possible msa by their certainty of diagnosis , and as msa with predominant parkinsonism ; msa - p or however , some findings of so - called red flags which do not support msa are also described . these red flags include dementia on diagnostic and statistical manual of mental disorders , fourth edition . therefore , the presence of dementia can exclude the diagnosis of msa according to these criteria . however , some recent studies have reported 2040% prevalence of cognitive impairment in msa.3 the cognitive impairment in msa is usually characterized by predominant impairment of frontal lobe functions , such as executive functions , than memory impairment.1,4 patients with msa - p showed more severe and diffuse cognitive impairments than patients with msa - c.5 comparing msa with other -synucleinopathies,6 the severity of cognitive decline was more than pd , but milder than dlb . compared to patients with dlb , patients with msa have a lesser impairment in the memory function . however , the visuospatial function and executive function were more damaged in patients with msa . patients with msa and dementia demonstrated frontal lobe atrophy in mri and decreased perfusion in the frontal and posterior parietal lobes in single photon emission computed tomography.3,4 with regard to temporal relationship of onset between motor symptoms and cognitive impairment in msa with dementia , patients with msa preceding dementia showed alzheimer s disease ( ad)-like pattern of cognitive impairment , severe memory deficits and more confusion than msa preceding motor symptoms.3 moreover , imaging studies revealed more diffuse cortical atrophy and severe white matter changes in patients with msa preceding dementia . unlike the previous studies , our patient showed severe cognitive impairments in msa - c and the pattern of cognitive deficit was different from ad despite of preceding dementia . the pathogenic mechanisms of cognitive impairment , especially frontal lobe dysfunction in msa are unclear . the clinical presentation and the frequency of cognitive impairment in msa may differ from that of other synucleinopathies such as dlb and pd with dememtia ( pdd ) , so it is possible to presume that the mechanisms of cognitive impairment in msa might be different with dlb and pdd . given that the various involvements of cortico - subcortical pathways in msa,7 aberrant circuits projecting from striato - nigral system to frontal lobe may be related . although frontal lobe dysfunction was prominent in this patient , metabolism in both parietal lobe and posterior cingulate gyrus was lower than that of frontal lobe . given that the [ f]-fdg pet findings are similar to the pattern of ad,8 the pathology of ad such as amyloid plaque or tau - positive neurofibrillary tangle may contribute to cognitive impairment related with msa . decreased level of beta amyloid peptide 42 in csf and tau protein observed from autopsy in msa patients may support this hypothesis.9,10 we report a msa patient who has developed cerebellar ataxia after diagnosed with dementia . this case may suggest that the clinical diagnosis of msa could not be excluded by the presence of dementia .

multiple system atrophy ( msa ) is a sporadic , adult - onset disease characterized by progressive degeneration of nervous systems including cerebellar , pyramidal , extrapyramidal , and autonomic system . although a few recent studies reported that cognitive impairments could occur in patients with msa , prominent dementia with progressive decline is not a typical clinical manifestation of msa . in particular , dementia with msa - cerebellar type is very rare . we have experienced a patient with 2-year history of severe cognitive impairment , who was finally diagnosed as msa - cerebellar type .

a 22 year old female with new onset of generalized seizure activity of unknown cause underwent a head computed tomography ( ct ) examination that revealed focal hypo - density within the left frontal bone , consistent with fibrous dysplasia and extended back into the left parietal bone as well ( figure 1 ) . despite anti - convulsant medication , additional nocturnal generalized seizure events recurred , prompting a whole body bone scan that was negative except for focally elevated 99mtc - mdp uptake in the left frontal - parietal region ( figure 1 ) . positron emission tomography ( pet ) imaging failed to reveal any focal metabolic defect within the brain ( figure 1 ) and displayed a slight diffuse prominence to fdg uptake within the left frontal - parietal bone . magnetic resonance imaging of the brain also failed to reveal any significant abnormalities but did also show the area of fibrous dysplasia to have mildly prominent t2 signal as seen on the t2 weighted axial section ( figure 1 ) . electroencephalography ( eeg ) examination revealed a persistent asymmetry in activity in the left frontal leads , with activity from this region being of higher voltage and better defined ( figure 1 ) than right hemispheric activity ( figure 1 ) . no definite epileptogenic discharges were revealed but did suggest episodic left frontal sharp wave activity compared to the right , but in retrospect , this appears to be of an artifactual nature due to the reduced resistance to current flow across the area of fibrous dysplasia , which apparently conducts eeg potentials with less impedance . fibrous dysplasia is often a benign incidental disorder where normal bone is replaced by fibrous connective tissue and can be at one location ( monostotic ) or less frequently seen at multiple sites on bone scan ( polyostotic ) . easily identified on bone scan as an area of focally increased tracer uptake within ct hypodense areas , the lesion often has low levels of metabolic activity on pet scan , but exceptions have been reported . other pet tracers can better characterize the metabolic profile of the lesion through the use of 11c - methioinine or 11c - choline . in only 4 to 10 % of cases a small number of case reports on the coexistence of fibrous dysplasia with epilepsy are noted with some of these reports suggesting a causative inter - relationship , which clearly seemed not be the case for the patient discussed here , and seemed to be incidental . however , the important unique finding of this case , not previously reported elsewhere , is recognition that misleading eeg interpretations can occur if the electrical conductance properties of focal fibrous dysplasia affecting the skull is not accounted for . in this case , an apparent asymmetry in waveform amplitude and definition appeared from the left frontal leads , similar to the well known breach rhythm phenomenon that occurs over post - surgical skull defects . although a breach rhythm effect has not been previously reported with fibrous dysplasia , a case of something similar in summary , monostotic fibrous dysplasia of the skull can be found on ct and /or brain magnetic resonance imaging and needs to be taken into account when interpreting eeg activity recorded over the involved region , as diminished resistivity to current flow is likely and produces an apparent asymmetry in waveform definition and amplitude , with the underlying activity being easier to record and more apparent . in conclusion , focal egg asymmetries related to focal fibrous dysplasia of the skull represent a form of breach rhythm with regards to its electrographic classification .

an unusual pervasive and persistent asymmetry in background rhythm was found on surface electroencephalography ( eeg ) recordings in a 22 year old with new onset of generalized seizure activity . radiographic correlation with computed tomography , positron emission tomography and bone scan imaging uncovered that the higher amplitude left frontal - parietal background activity was related to a circumscribed area of left frontal - parietal fibrous dysplasia affecting the skull . this case report emphasizes that the presumed higher electrical conductance of fibrous dysplasia lead to a greater transparency of normal background rhythms , and must be taken into account as a form of breach rhythm for accurate eeg interpretation

in the early 1970s , this picture of thymic selection was still being colored in . immunologists were unaware that the antigens recognized by t cells were peptides bound to mhc molecules . and tcrs themselves peter doherty laid out the nobel prize winning rules of what is now known as self - mhc restriction in 1973 . they showed that antiviral t cells from an immunized mouse only recognized infected cells from other mice that shared the same type of mhc genes ( 1 ) . one for a self - mhc molecule , and the other for the viral antigen ( 2 ) . but zinkernagel and doherty preferred their own altered - self hypothesis , which proposed that the t cells bore a single receptor that recognized an mhc molecule that had been somehow altered by the viral infection . michael bevan , then a postdoctoral fellow at the salk institute ( san diego , ca ) , was intrigued by the altered - self theory . he had been studying differences in the genes encoding minor histocompatibility antigens ( mhas ) that cause graft rejection even when donors and recipients are mhc matched . he found that recognition of target cells by t cells specific for mha also followed the rules of mhc restriction . he proposed that the t cells recognized self - mhc molecules that were associated with these mhas and called it the antigen interaction hypothesis . the nature of this altering the binding of peptides to self - mhc would not be known for a few more years . bevan was able to boost confidence in the altered - self theory by disproving the two - receptor hypothesis . he found that in the progeny of mhc - a and mhc - b mice , individual t cells recognized antigen on either mhc - a or mhc - b cells but not both . in the dual recognition theory , each t cell would have had receptors for both mhc molecules and thus would have recognized both targets . as a further test of his theory , bevan designed an assay in which cells that had either the correct mhc but the wrong mha or vice versa competed with cells that had both the correct mhc and mha as targets for killing by mha - specific t cells . he found that both the correct mhc and mha had to be on the same target cells to be recognized by the t cells . an enticing explanation for these data was that the self - mhc and the antigen were somehow interacting . bevan published these results in the journal of experimental medicine in 1975 ( 3 ) . a previous hypothesis suggested that t cells were selected in the thymus ( 4 ) . bevan tested this theory by injecting t cell precursors from the progeny of mhc - a and mhc - b parents into lymphocyte - deficient mhc - a recipients . newly generated t cells from these mice recognized antigen - presenting target cells from mhc - a but not mhc - b mice . furthermore , when the thymus of the progeny mouse was replaced with an mhc - a only thymus , most of its t cells only recognized antigen bound to mhc - a cells ( 5 ) . bevan concluded that the mhc molecules in the thymus determine what mhc molecules will be recognized by the t cells . the definition of the tcr structure finally vindicated the single receptor hypothesis ( 6 ) . tcrs were later shown to recognize peptide fragments bound to mhc molecules on antigen - presenting cells ( 7 ) .

in the 1970s , michael bevan showed that t cells only recognize antigens in cells that have the same type of major histocompatibility complex ( mhc ) molecule present in the thymus where the t cells mature . his work provided the first clues to how thymic self - mhc molecules select the cells that make up the mature t cell repertoire .

hereditary angioedema ( hae ) is a rare disease that usually occurs in adolescence and early adulthood . the disease is characterized by the recurrent , self - limited attacks of non - pitting edema . this disease is inherited as an autosomal dominant trait and caused by the deficiency of c1 esterase inhibitor ( c1-inh ) resulting in activating classic complement pathway . hae may be associated with autoimmune diseases , such as systemic lupus erythematosus , rheumatoid arthritis , autoimmune thyroiditis and glomerulonephritis . idiopathic hypoparathyroidism may be developed by autoimmune mechanism as a part of polyglandular autoimmune syndrome or as an isolated hypoparathyroidism . a case of hae associated with idiopathic a 34-year - old male visited the emergency room because of involuntary movement of extremities and edema on the hand . he had no history of neck operation , trauma , transfusion and other developmental anomalies . he had suffered , for the last 10 years , from the clinical symptoms of hae with recurrent , self - limited cutaneous swellings and abdominal pain . one year ago , he had been treated with a mechanical ventilator because of laryngeal edema . serum total calcium , ionized calcium and phosphate levels were 5.8 mg / dl ( normal range 8.810.5 ) , 0.7 mmol / l ( normal range 1.051.35 ) and 5.7 mg / dl ( normal range 2.54.5 ) , respectively . parathyroid hormone and 1,25-oh2-vitamin d levels were less than 5 pg / ml ( normal range 1065 ) and 8.10 pg / ml ( normal range 2060 ) , respectively . c1-inh level and functional activity of chnh were 10.2 mg / dl ( normal range 1535 ) and less than 25% ( normal range 80125 ) , respectively . c1q , c3 , c4 levels and ch50 were 9.15 mg / dl ( normal range 12.419.0 ) , 77 mg / dl ( normal range 70150 ) , 5 mg / ml ( normal range 1040 ) and 6.4 ( normal range 3045 ) , respectively . the c4 level and functional activity of c1-inh of his family members were measured ( figure 1 ) . his monozygotic twin daughters showed low c4 level and decreased functional activity of chnh although they had never experienced clinical symptoms of hae . on the diagnosis of type i hae with idiopathic hypoparathyroidism , the patient was treated with calcium replacement and attenuated androgen ( danazol ) and the clinical manifestations were improved . hae is an autosomal dominant genetic disorder characterized by recurrent swelling of extremity , respiratory tract and bowel . two types of deficiency have been described ; type 1 with a low level of chnh antigen and the rare type 2 with a normal or elevated serum levels of dysfunctional c1-inh . c1-inh plays a central role in the regulation of the complement , coagulation and contact ( kinin - forming ) systems . as a member of the family of serine protease inhibitors , c1-inh acts as a suicide protein by forming complexes with the target proteases . it inhibits c1r and c1s in the complement system , factor xii and kallikrein in the contact system and factor xi in the coagulation system . patients with a deficiency of chnh have low plasma levels of c4 which is the substrate of the c1r - c1s complex . it has been reported that patients with hae have an increased incidence of immunoregulatory or autoimmune diseases . previous reports have emphasized the striking incidence of systemic lupus erythematosus , as well as membranoproliferative glomerulonephritis , in this patient group . in general , patients with hae have unregulated activation of the early steps of the classic complement pathway with decreased ( but not absent ) levels of c4 and c2 . decreased or dysfunctional complement may promote the tissue deposition of immune complexes and autoimmue disease because complement proteins play an important role in the clearance of immune complexes or autoantibodies . idiopathic hypoparathyroidism is sometimes associated with developmental anomalies , such as dwarfism , cortical thickening of tubular bones , nephropathy , sensorineural deafness and lymphedema . it has been reported that several genetic defects are associated with the development of idiopathic hypoparathyroidism . most of adult - onset idiopathic hypoparathyroidism may be developed by the mechanism of autoimmune basis . the association with other autoimmune disease is well established and the presence of autoantibodies to parathyroid cells provides further circumstantial evidence of an autoimmune etiology . in our case , we can assume that hae might be associated with hypoparathyroidism , as well as systemic lupus erythematosus , because of the genetically determined dysfunction of complement pathway . a casual association could not be excluded and further studies are needed to elucidate the detailed mechanism of these immune - based diseases .

hereditary angioedema is a rare autosomal dominant disease characterized by the edema of subcutaneous tissues , respiratory tract and bowel . it is caused by the deficiency of ci esterase inhibitor . hereditary angioedema may be associated with autoimmune diseases , such as systemic lupus erythematosus , rheumatoid arthritis , autoimmune thyroiditis and glomerulonephritis . we report a 34-year - old male patient with hereditary angioedema who developed idiopathic hypoparathyroidism . autoimmunity seems to be an important basis of this association and it might be caused by the immune dysfunction due to decreased level of complements ; nevertheless , a casual association could not be excluded . to our knowledge , this is the first report of hereditary angioedema in association with idiopathic hypoparathyroidism in the medical literature .

renovascular hypertension ( rvh ) due to renal artery stenosis ( ras ) is an important cause of severe hypertension . fibromuscular dysplasia ( fmd ) , takayasu 's arteritis , middle aortic syndrome and atherosclerosis are the common causes of ras . revascularization either by percutaneous angioplasty with or without stenting or by open surgical methods may be needed if medical therapy fails to control hypertension or there is progressive deterioration of renal function . among revascularization procedures , a 17-year - old male presented with shortness of breath , swelling of feet and oliguria of 2 months duration . he was found to have severe hypertension with impairment of renal functions and pulmonary edema . blood pressure ( bp ) in right upper and lower limbs were 270/120 mmhg and 210/120 mmhg , and the left upper and lower limb was 260/140 mmhg and 260/130 mmhg respectively . investigations showed serum creatinine 2.1 mg / dl , blood urea 62 mg / dl , sodium 139 mmol / l , potassium 3.1 mmol / l , blood sugar 86 mg / dl , haemoglobin 9.4 g / dl , total leucocyte count 7200/mm , erythrocyte sedimentation rate : 20 mm , serum uric acid 6.6 mg / dl , serum calcium 10.6 mg / dl , serum phosphorus 4.9 mg / dl , serum proteins : 7.1 g / dl , serum albumin 3.1 g / dl . urine examination showed protein : + , 46 white blood cell / hpf and 24 red blood cells / hpf . ultrasound showed right kidney measuring 8.9 cm 3.4 cm and left kidney 9.2 cm 4.0 cm with normal echotexture . . there was aortic regurgitation , moderate left ventricular systolic dysfunction and grade i left ventricular diastolic dysfunction . right renal artery showed a peak systolic velocity of 31 cm / s while the left renal artery had a peak systolic velocity of 46 cm / s . proximal aorta showed diffuse wall thickening and decreased caliber ( aorto arteritis with b / l proximal ras of > 90% ) . computed tomography ( ct ) angiogram showed 6070% stenosis of renal arteries at origin bilaterally [ figure 1 ] . bilateral renal artery stenoses conventional angiogram showed diffuse concentric thickening of distal thoracic and upper abdominal aorta with bilateral long - segment occlusion of main renal arteries with distal renal arteries filling through collaterals . patient was on clonidine 0.2 mg tid , nifedipine retard 20 mg tid , prazosin xl 5 mg bid , carvedilol 3.125 mg bid and torsemide 20 mg bid . with above medications , as both renal arteries had long - segment stenosis proximally with good distal caliber , splenrenal arterial anastomosis was planned . one centimeter stump of the renal artery ( 6 mm diameter ) was felt in the hilum , dividing into upper and lower divisions . the splenic artery was identified and anastomosed with left renal artery end to end ( splenorenal anastomosis ) . on 2 postoperative day bp was 140/84 mmhg with nifedipine 20 mg 1 tablet tid . postoperative doppler showed good filling of left distal renal artery through the splenic artery with good renal perfusion . ct angiogram was performed on 10 postoperative day that demonstrated patent splenorenal arterial anastomosis [ figure 2 ] . patient was discharged on 10 postoperative day with advice for right kidney revascularization after 2 months . the common causes of rvh in our country are takayasu 's arteritis , fmd and atherosclerosis . rvh is amenable to treatment with anti - hypertensive drugs , and revascularization is required only for uncontrolled hypertension or for the preservation of renal function . percutaneous transluminal renal angioplasty ( pta ) has good success especially for fmd but in extensive aortic disease or bilateral stenosis ptra is not used . open surgical techniques include aortic bypass e.g. , aortorenal bypass using saphenous vein , hypogastric artery or a prosthetic graft . in patients with difficult aortic surgery , . the arterial wall may be friable in the acute stage hence surgery should be avoided in the acute stage . selection of technique depends on each individual case , the clinical situation , and the preference of the individual surgeon . in addition , the status of the contralateral renal artery and the existence of any other vascular lesion must be evaluated , particularly associated arteriosclerotic disease of the abdominal aorta . autogenous saphenous vein , hypogastric artery or a prosthetic graft may be employed , depending on individual requirements and preference of the surgeon . use of polytetrafluoroethylene as graft material increases the risk of thrombosis and infection ; use of saphenous vein is technically difficult because of its small size ( 2 mm diameter ) and has been associated with aneurysmal degeneration and sub - intimal hyperplasia . occasionally , saphenous vein may be absent or inadequate in caliber , or in some instances may be better preserved for possible future use in aortocoronary or femoropopliteal reconstructions . autogenous hypogastric artery represents an ideal graft material , but its usefulness is often limited by associated arteriosclerosis and the requirement for dissection in a far removed operative field . since that time scattered reports have appeared , the largest of which is survey by khauli et al . kaufman and myers and johnson found it technically challenging ; however , reports by brewster et al . show that it is a simple and safe procedure . the risk of infection and thrombosis is reduced by avoiding the use of foreign materials / artificial grafts . the procedure is suitable for a staged approach to bilateral disease or in reoperation for failed prior reconstructions . in a paper by brewster et al . there were no deaths , and a single failure occurred due to graft occlusion ( 5% ) . of the remaining 18 patients , 7 were cured and 11 improved . there were no cases of postoperative renal failure , and renal function improved in all four patients with renal failure preoperatively . in selected patients , good preoperative angiographic evaluation of coeliac axis and splenic artery is needed when splenorenal graft is considered . adequate lateral and often oblique films should be obtained to exclude any associated lesions that may contraindicate the use of splenic artery . the technique is effective , safe and requires a single vascular anastomosis . in our case , this technique was chosen as the diseased aorta and long - segment proximal stenosis of renal arteries precluded the use of these vessels . endarterectomy may be employed for focal arteriosclerotic lesions ; however , it is not suited to stenoses associated with significant aortic arteriosclerosis and is inapplicable in fmd . in this case report , we highlight the role of splenorenal bypass in the management of refractory rvh .

renovascular hypertension can be managed medically in most cases . however , in cases of failed medical therapy revascularization is indicated . splenorenal grafting is one such method for revascularization . we present a report of splenorenal grafting for the management of resistant hypertension .

dermatofibrosarcoma protuberans is a relatively rare skin tumor characterized by a low potential of malignancy . dermatofibrosarcoma of darier - ferrand or dermatofibrosarcoma protuberans ( dfsp ) is a rare cutaneous mesenchymal tumor characterized by a low potential of malignancy with a very low rate of metastasis but a rate of local recurrences rather important . the authors report the epidemiologic , clinical , histological , therapeutic , and evolutionary characteristics of the disease . we report the case of a 19-year - old female , without any pathological history , presenting a cutaneous mass of the lower third of the right upper leg that appeared 7 years ago . the clinical study showed an 8 cm diameter mass located on the anterior and internal side of the distal third of the right upper leg . it was dependent on the superficial cutaneous tissues and evoking a tumor of darier and ferrand [ figure 1 ] . no weight loss was noted . no systemic adenopathy or signs of distant metastasis were found on the chest , abdomen , and pelvis computed tomography scan . a magnetic resonance imaging study of the right lower extremity revealed an 8 cm 8 cm 5.7 cm well limited , vascularized , round mass in the cutaneous , and subcutaneous tissues [ figure 2 ] . the patient underwent a 5 cm margin excision involving in - depth the aponeurosis with resection margins microscopically negative [ figure 3 ] . the histological study revealed a malignant transformation of the dermatofibrosarcoma of darier and ferrand into a sarcoma [ figures 4 and 5 ] . there was no recurrence at 5 years follow - up [ figures 6 and 7 ] . clinical aspect of the mass evoking a tumor of darier and ferrand magnetic resonance imaging noted a well limited , vascularized , round mass of cutaneous and subcutaneous tissues resection of the tumor with a margin of excision of 5 cm involving in - depth the aponeurosis . the residual skin defect was grafted histological aspect revealing a malignant transformation of the dermatofibrosarcoma of darier ferrand into a sarcoma ( h and e stain , 100 ) tumoral proliferation in spindle - shaped cells ( h and e stain , 400 ) the esthetic and functional result was assessed as good at 5 year follow - up the esthetic and functional result was assessed as good at 5 year follow - up the transformation of a dermatofibrosarcoma of darier and ferrand into an fs ( fs - dfsp ) is exceptional , until now and since the first description of a metastatic dfsp by penner in 1953 , only 100 cases of fs - dfsp were reported . the dfsp generally occurs in the trunk ( 47% ) , the upper limb ( 38% ) , or the cervico - cephalic area ( 15% ) . this tumor generally begins with a single swelling , hardened by place , brown - red , purplish . after several years ( a few decades ) , one or more nodules become rising protuberant . after a long time superficial growth , this tumor will invade the deeper layers extending along the fascia . no significant clinical difference was noted between fs - dfsp and the traditional form . the tumoral proliferation of the dfsp interests cutaneous and sub cutaneous layers of the skin ; it is made up of spindle - shaped cells with few atypies and mitosis . in the periphery , the tumoral cells are arranged in great corrugated and flexuous beams loose parallelism at the surface . in depth , the tumor infiltrates the sub - dermal in tablecloth dissociating the fat lobules and takes the form of interlobular partitions . it can extend from the primary zone , reaching the underlying fascia or aponeurotic layer . the tumoral cells of the dfsp express the cd34 in 90% of the cases and factor xiii . the fs - dfsp is defined histologically by the presence in a cellular dfsp of ranges pointing towards an fs , the transition is abrupt or gradual . the treatment of these cutaneous tumors , mainly surgical , is based on broad resection in the case of malignant tumor . adjuvant radiotherapy can be used to obtain local control when the resection margins are microscopically positive or when wide excision results in a significant functional or esthetic deficiency . their frequencies depend on the margins of the initial excision : 40% if they are 2 cm , 1020% for margins of 3 cm , and 1.75% for margins of 4 cm . in all the cases the relationship between the presence of fibrosarcomatous foci with locoregional or metastatic evolution remains controversial . the rate of locoregional recurrence of the fs - dfsp depends on the quality of the resection , without a significant difference compared to dfsp . on the other hand , the free interval , preceding the possible recurrence , could be shortened ( usually < 2 years ) compared to the traditional form . a large study published by mentzel et al . showed an association between the presence of fibrosarcomatous foci and significant metastatic potential . in this study , approximately 15% of the patients developed primarily pulmonary metastases without significant association with the prognostic factors such as the size of the lesions , the mitotic activity or the presence of necrosis . the dfsp is a rare tumor , its diagnosis is histological , and its treatment is surgical . this transformation seems to be in association with a significant metastatic potential estimated at 15% . the identification of fibrosarcomatosis implies a complete assessment of extension and a closer follow - up . the transformation of dfsp into a fs is exceptional and comes with a high potential of malignancy . the transformation of dfsp into a fs is exceptional and comes with a high potential of malignancy . the transformation of dfsp into a fs is exceptional and comes with a high potential of malignancy .

dermatofibrosarcoma protuberans is a rare cutaneous mesenchymal tumor characterized by a low potential of malignancy with a very low rate of metastasis but an important rate of local recurrence . its transformation into a fibrosarcoma is exceptional , responsible for a higher metastatic potential . this transformation implies a closer surveillance . through a case report and literature review , we will try to expose epidemiological , clinical , histological , therapeutic , and outcome particularities of this entity .

mucinous cystic tumors of the ovary rarely contain one or more solid mural nodules in which the histological features differ markedly from the background of benign , borderline or malignant mucinous neoplasms . four varieties of mural nodules have been described , including true sarcomas , sarcoma - like mural nodules ( slmn ) , foci of anaplastic carcinoma and mixed type . slmn stend to occur in younger women and are characterized by smaller size , sharp demarcation , a heterogeneous cell population , and no serious impact on the prognosis . it should be differentiated from true sarcomatous mural nodules and foci of anaplastic carcinoma with areas of sarcomatoid differentiation since both of these lesions carry a graver prognosis . we report a very rare case of slmn in a borderline mucinous tumor of the ovary . a 30-year - old unmarried female patient presented with progressive abdominal enlargement for last 7 months . she also complained of mild lower abdominal pain and discomfort for last 2 and half months . a cystic swelling of about 18 - 20 weeks size reaching just below the level of umbilicus was felt on physical examination . ultrasonography revealed a left ovarian cystic space - occupying lesion(sol ) of 12 cm 9.6-cm size with internal echogenicity and septations . grossly the cystic ovarian mass [ figure 1a ] measured 13.8 cm 12 cm 8 cm . an elevated firm , well - definednodular area measuring 4.8 cm 3.6 cm 2.5 cm was noticed on the inner surface of the largest locule . microscopic examination displayed the histopathological features of a borderline mucinous tumor showing complex cribriform architecture with mild to moderate cellular atypia along with an adjacent circumscribed nodular area [ figure 1b and d ] . however , no recognizable glandular structures infiltrating into the deeper part of the nodule were identified . the nodular area was predominantly composed of pleomorphic spindle cells with hyperchromatic nuclei and occasional prominent nucleoli arranged in a vaguely fascicular pattern . the pleomorphic cells focally demonstrated smooth muscle and rhabdomyoblastic differentiation [ figure 2a and b ] . frequent mitotic figures including atypical forms admixed with histiocytes and inflammatory cells especially eosinophils were noticed . immunohistochemistry for cytokeratin was focally positive and vimentin was diffusely positive in the pleomorphic spindle cells of the nodule . overall , the histopathogical features of the nodule closely mimicked that of a sarcoma except the presence of circumscription and absence of vascular invasion . true sarcoma , atypical inflammatory myofibroblastic tumor , carcinosarcoma were considered as differential diagnoses . however , considering the circumscription of the nodule in macroscopy as well as in microscopy along with corroborative histopathological and immunohistochemical findings , the diagnosis of a borderline mucinous tumor with slmn was made . ( a ) mucinous cystic neoplasm of ovary with mural nodule ( b ) a well - circumscribed slmn alongwith borderline mucinous tumor ( h and e , 100 ) ( c ) a cellular well - demarcated nodular area of slmn ( h and e , 100 ) ( d ) complex atypical cribriform glands of borderline mucinous neoplasm ( h and e , 400 ) ( a ) photomicrograph showing prominent mitotic figures and smooth muscle differentiation in slmn ( h and e , 400 ) ( b ) rhabdomyoblastic differentiation in slmn ( h and e , 400 ) ( c ) photomicrograph showing coagulative necrosis in slmn ( h and e , 400 ) ( d ) atypical mucinous glands showing strong cytokeratin positivity and spindle cells of the nodule in the background displaying focal and weak cytokeratin positivity ( h and e , 100 ) in 1979 , prat and scully reported 14 cases of slmns , seven of them from the previous literature , and pointed outtheir favorable clinical behavior . they described three types of morphology in slmns namely pleomorphic and epulis type , pleomorphic and spindle cell type and giant cell - histiocytic type . sarcomatous nodules can exhibit a variety of patterns , including fibrosarcoma , rhabdomyosarcoma , and undifferentiated sarcoma . mixed nodules may feature carcinosarcoma or a mixed anaplastic carcinoma and sarcoma - like nodule . the present case displayed the morphology similar to the pleomorphic and spindle cell type with areas of smooth muscle and rhabdomyoblastic differentiation . in contrast to slmns , the sarcomatous nodules and foci of anaplastic carcinoma which can also present as mural nodule , tend to occur in older patients and are characterized by larger size , poor circumscription , a monotonous spindle cell population in the former , evidence of carcinomatous differentiation in the latter , and aggressive behavior . anaplastic carcinomatous nodules generally have spindled and rhabdoid cells with unequivocal cytologic features of a high - grade malignancy , and are associated with intraepithelial or invasive mucinous carcinoma in 72% of cases . atypical inflammatory myofibroblastic tumors may resemble slmns possibly due toa florid reaction to intramural hemorrhage or spilling of mucinous material in cystic ovarian tumors . in contrast to slmns that occur in association with an epithelial tumor , inflammatory myofibroblastic tumors have a predilection for relatively younger patients , appear de novo , and are larger and less well circumscribed . although various hypotheses have been proposed to explain the histogenesis of the slmns , it probably represents a reactive and self - limited phenomenon within a neoplasia . slmns usually strongly express vimentinand focally or weakly express cytokeratin , similar to true sarcomas yet distinct from anaplastic carcinomas that usually have strong / diffuse cytokeratin expression . finally the age of the patient , well circumscription of the nodule and lack of vascular invasion were the only parameters that led us to the correct diagnosis . the outcome of mucinous tumors with slmns is the same as the corresponding category of mucinous tumors without the nodule . but slmns should be regarded with caution as their histologic appearance is worrisome and clinical follow - up data are very limited . hence , careful and meticulous examination of this rare lesion within a mucinous cystic tumor is essential for reassuring the patient of a favorable clinical outcome and for excluding the similar looking aggressive lesions having poorer outcome .

sarcoma - like mural nodule ( slmn ) is a very uncommon and misleading benign entity which may be associated with benign , borderline or malignant mucinous neoplasm of the ovary . it should be distinguished from other malignant mural nodules with sarcoma , carcinosarcoma or anaplastic carcinoma for proper management . we report a rare case of slmn in a borderline mucinous tumor of the ovary in a 30-year - old lady . in spite of having confusing histopathological features the final diagnosis was made depending on the younger age of the patient , well circumscription of the nodule , absence of vascular invasion and immunohistochemical profile .

simultaneous electrical stimulation of both ventricles in patients with interventricular conduction disturbance and advanced heart failure improves hemodynamics and results in increased exercise tolerance , quality of life [ 1 - 3 ] . our approach is based on transthoracic dynamic three - dimensional ( 3d ) echocardiography and allows determination of the most delayed contraction site of the left ventricle ( lv ) together with global lv function data . we use a self - developed fast rotating transducer , which is connected to a commercially available ultrasound system ( ge vingmed vivid five , horton , norway ) . the 64-element phased - array transducer has a center frequency of 3 mhz , second harmonic capabilities and continuously rotates inside the transducer assembly at 8-revolutions/ sec . during resynchronization device implantation , images are obtained with the patient in the left lateral decubitus position with the transducer in the apical position and the image plane rotating around the lv long axis . images are acquired in sinus rhythm and in two different pacing modes : during right ventricular apical pacing and biventricular pacing . with a self - developed software , using matlab ( the mathworks , inc , natick , ma , usa ) , the original 2d images are post - processed by placing them in their correct spatial and temporal ( ecg reference ) position using multi beat data fusion . all the cross - sectional images re - sampled from each dataset are subsequently imported into the tomtec4d lv - analysis software ( tomtecimaging systems gmbh , germany ) for automated endocardial border detection . subsequently , the program performs a dynamic surface rendered endocardial reconstruction of the lv in sinus rhythm and in the different pacing modes . for each pacing mode , a time volume curve ( tvc ) is plotted from which global end - diastolic ( lvedv ) , end - systolic volumes ( lvesv ) and ejection fraction ( ef ) are calculated . the lv endocardial surface is subdivided in 16 segments , which are color - coded for orientation . the difference in time to maximal myocardial contraction between segments is used to assess and measure regional mechanical delay and dyssynergy ( movies 1 , 2 and 3 see additional file 1 , additional file 2 and additional file 3 respectively ) . our initial results suggest that fast reconstruction of the lv is feasible for the selection of the optimal pacing site and allows identifying lv segments with dyssynchrony . however , real time three - dimensional echocardiography is now available , and the optimal pacing site can be determined on - line . our major finding is that transthoracic dynamic 3d echocardiography performed by a fast rotating transducer and combined with automated contour analysis is feasible to determine mechanical asynchrony during lv contraction . additionally , it is capable of hemodynamic evaluation and therefore may be advantageous as compared to tdi . our data suggest that this method may be useful for evaluation and guiding resynchronisation device implantation . tissue doppler imaging ( tdi ) is the imaging modality , which is currently used to assess the most delayed ventricular site before implantation of a resynchronisation device . although the method is proven to be feasible , it is uncomfortable to use online and , most importantly , assessment of the hemodynamic effect requires additional and separate studies . the aim of our project was to develop and test the feasibility of an alternative approach for determining the optimal pacing site . our proposed method , based on 3d echocardiographic time - volume curves ( tvc ) , includes additional features such as hemodynamic evaluation by measuring true ventricular volumes . previous studies demonstrated that generation of tvcs , representing lv volume changes over the cardiac cycle , is feasible and accurate and allows detailed quantitative analysis of lv performance , even in patients with lv dysfunction . three - dimensional reconstruction of the left ventricle in sinus rhythm ( 1 ) the time - volume curves of four different segments are displayed under the three - dimensionally reconstructed ventricles . the endocardial surface is subdivided in 16 color - coded segments . during sinus rhythm , right ventricular pacing significantly changes the activation pattern , but asynchrony is still present . the right ventricular apical segments contract early , at the site of the position of the right ventricular pacing lead . the largest delay is in the lateral wall in both sinus rhythm and right ventricular apical pacing . during biventricular pacing , three - dimensional reconstruction of the left ventricle in , right ventricular ( rv ) pacing . for more information please see the text for additional file 1 three - dimensional reconstruction of the left ventricle in the biventricular pacing modes . for more information

simultaneous electrical stimulation of both ventricles in patients with interventricular conduction disturbance and advanced heart failure improves hemodynamics and results in increased exercise tolerance , quality of life . we have developed a novel technique for the assessment and optimization of resynchronization therapy . our approach is based on transthoracic dynamic three - dimensional ( 3d ) echocardiography and allows determination of the most delayed contraction site of the left ventricle ( lv ) together with global lv function data . our initial results suggest that fast reconstruction of the lv is feasible for the selection of the optimal pacing site and allows identifying lv segments with dyssynchrony .

although metastatic gastric tumors are uncommon , gastric metastasis from ovarian carcinoma is extremely rare because malignant cells from the ovary usually spread through the intraperitoneal cavity.1 - 3 here , we report a case of gastric metastasis from ovarian adenocarcinoma presented as a submucosal tumor without ulceration . a 49-year - old woman presented to our department for evaluation of a gastric mass . fifty - two months previously , she had undergone a total abdominal hysterectomy with bilateral salpingo - oophorectomy and pelvic lymph node dissection for serous ovarian adenocarcinoma and anterior resection for colon metastasis . after the surgery her ca-125 level returned to normal following completion of chemotherapy and she was in good condition for 44 months until her serum ca-125 level increased to 160.1 u / ml ( reference value 35 u / ml ) . an f-18 fluorodeoxyglucose positron emission tomography ( fdg - pet ) scan revealed a high - uptake lesion in the wall of the gastric antrum and presacral area ( fig . abdominal ct showed pelvic fascia thickening , although there was no evidence of gastric metastasis or carcinomatosis peritonei . subsequent endoscopic examination was performed and showed a 2.52.5 cm sized submucosal tumor ( smt ) covered with normal gastric mucosa at antrum ( fig . 2 ) . endoscopic ultrasound ( eus ) examination demonstrated that the lesion was invaded to the proper muscle layer and was surrounded by a well - demarcated hypoechoic rim with an intact mucosal layer ( fig . we performed an esd with enucleation for the entire lesion without complication using hook knife because the patient did not want surgical resection ( fig . histopathologic examination revealed submucosal growth of the papillary tumor originating from the previous ovarian carcinoma ( fig . the patient is currently receiving chemotherapy ( docetaxel and cisplatin ) and is in good condition without any additional metastasis for 18 months . metastasis to the stomach from ovarian carcinoma is a rare clinical event,1 - 3 as ovarian carcinoma usually seeds through the peritoneum and carcinomatosis peritonei is the most common form of distant metastasis after curative resection or chemotherapy . however , as described here , ovarian carcinoma may metastasize to other organs including the stomach through the blood stream without any evidence of peritoneal metastasis . although the stomach receives a rich blood supply , there has been no report to clarify gastric metastasis from distant organs hematogenously . metastatic gastric tumor usually presents as an ulcerated lesion on the luminal side and appears as a volcano or mass.4 - 7 here , we report a metastatic gastric tumor originating from an ovarian carcinoma , presented as an smt , reminiscent of gist . there has been a report of a metastatic gastric tumor originating from ovarian carcinoma presented as a bleeding lesion , which was diagnosed easily with egd , and metastasis was confirmed with surgical resection.3 however , surgical intervention is an invasive procedure and it can be a burden for the patient . therefore , a less invasive diagnosis is required . another option for the histopathologic diagnosis of smt - like lesions is an eus - guided fine needle aspiration of the lesion . this technique has shown high sensitivity and specificity in many studies,8,9 although the equipment is not available in most institutes in korea . when eus - guided aspiration biopsy is not available , esd with enucleation may be a viable second option because it is less invasive than surgical intervention and can be performed in the majority of the institutes in korea . in summary , smt of the stomach in patients with ovarian carcinoma should not be overlooked and esd with enucleation may be a viable option when eus with fine needle aspiration is not available . to our knowledge , this is the first reported case of gastric metastasis of ovarian carcinoma presented as an smt without ulceration in the english literature .

metastatic gastric cancer is extremely rare and gastric metastasis from ovarian adenocarcinoma has rarely been reported . all of the previously reported metastatic lesions presented as an ulcerative lesions . we report a case of 49-year - old woman in which gastric metastasis from ovarian adenocarcinoma presented as a submucosal tumor without ulceration on endoscopic examination . gastrointestinal stromal tumor was suspected on endoscopic ultrasound ( eus ) examination . it was confirmed histopathologically as metastatic ovarian adenocarcinoma after endoscopic submucosal dissection ( esd ) with enucleation . submucosal tumor of the stomach in patients with ovarian carcinoma should not be overlooked and esd with enucleation may be a viable option when eus with fine needle aspiration is not available .

neuroendocrine neoplasm can occur in any organ of the body , yet it is generally localized in the gastrointestinal system or the bronchial system . ( 1 ) in 1969 first described laryngeal neuroendocrine neoplasm as a distinct clinical and pathologic entity , and over 500 cases of this neoplasm have been reported in the english literature since then . the clinical behavior and overall prognosis show wide variations between the different tumor types . in this article , we describe a rare case of a moderately differentiated neuroendocrine carcinoma of the larynx and we summarize the current literature regarding this unusual tumor ( 2 - 4 ) . a 59-yr - old man with a history of heavy smoking presented with a change of voice that he 'd experienced for one month . on laryngoscopic examination , a submucosal mass was seen on the laryngeal surface of the epiglottis . two enlarged lymph nodes were palpable on the neck examination at the left level ii and iii areas . 2 ) . the ct scan demonstrated a supraglottic mass invading the pre - epiglottic space , and there were multiple metastatic neck nodes at the left level ii and iii areas ( fig . no distant metastatic lesion was noted on the chest x - ray , abdominal sonogram , gfiber exam and bone scan . the histopathology of the surgical specimens revealed moderately differentiated neuroendocrine carcinoma with a tumor - free resection margin . the patient 's postoperative course was not complicated except for a chyle fistula that was resolved with conservative management . postoperative radiation treatment was done on the location of the primary tumor and both neck areas . at the 6 months postoperative follow - up exam , the patient complained of back pain with a tingling sense in the lower leg . multiple metastatic lesions at the t7 and t11 levels with a compression fracture at the l2 level were identified on the spine mri scan ( fig . radiation therapy was administered on the lumbar spine for the pathologic fracture and palliative chemotherapy was also performed , but the patient died from his cancer 3 weeks later . although neuroendocrine neoplasm of the larynx is uncommon , it is the most common non - epidermoid neoplasm of this organ . the epithelial origin tumors are further subclassified based on the degree of differentiation ( well , moderately , and poorly differentiated carcinoma ) . well differentiated neuroendocrine carcinoma ( typical carcinoid ) is an extremely rare subtype and it carries the best prognosis . this tumor is preferably treated by conservative surgery unless this is expensive , and elective neck dissection is not indicated . poorly differentiated or small cell neuroendocrine carcinoma is similar in appearance and behavior to small cell lung carcinoma . it is the most highly malignant neoplasm with frequent metastases and a poor survival rate . the same as for small cell lung carcinoma , chemotherapy , and radiation therapy are the preferred treatment modalities ( 2 , 5 , 6 ) . the neuroendocrine neoplasm that 's caused the greatest diagnostic confusion for moderately differentiated neuroendocrine carcinoma is laryngeal paraganglioma . however , its biological behavior is typically benign ( 2 , 3 , 7 ) . complete surgical resection is the treatment of choice ; elective neck dissection is not necessary and metastasis is very rare . overall , the prognosis for patients with this tumor is excellent ( 2 , 8) . moderately differentiated neuroendocrine carcinoma ( atypical carcinoid ) is the most common neuroendocrine tumor of the larynx . it is more common in the older age men ( 6th decade ) who have a history of cigarette smoking . the diagnosis may be difficult , especially on the initial biopsy evaluation , but making a precise diagnosis is crucial for selecting the proper therapy and achieving a good patient outcome . in contrast with well differentiated laryngeal tumor , mitosis , cellular pleomorphism , and necrosis are the critical features for the diagnosis . carcinoma cells are usually positive for markers such as chromogranin , synaptophysin , keratin , calcitonin and carcinoembryonic antigen . the final diagnosis should not be based solely on the presence or absence of a single immunohistochemical stain marker , and a panel of immunohistochemical antibodies should be utilized ( 3 , 5 , 8) . unlike well differentiated laryngeal tumor , moderately differentiated neuroendocrine carcinoma of the larynx is an aggressive and potentially widely metastasizing malignancy . nodal metastases are frequent and distant metastases are not uncommon ( 2 ) . the ideal therapy remains a subject of debate . complete surgical removal is recommended and supraglottic laryngectomy is often indicated when considering the primary site of the lesion . bilateral elective neck treatment should be performed for the n0 cases because of the high risk of cervical lymph node metastases . this tumor is reported to be radiotherapy and chemo therapy resistant . however , the addition of radiation therapy appears warranted for cases of local extension , multiple nodal metastases or extracapsular disease ( 5 , 8 , 9 ) . ( 10 ) reported that elevated calcitonin levels could be regarded as a specific marker for laryngeal atypical carcinoid . ( 2 ) revealed that an elevated serum calcitonin level was almost always present in patients with medullary thyroid carcinoma , but an elevated serum calcitonin level has been only occasionally reported in patients with atypical laryngeal carcinoid . future studies will be required to investigate the role of calcitonin as a postoperative follow - up tool . in a minority of cases , paraneoplastic syndrome may precede the clinical manifestation of persistent or recurrent tumor , or asymptomatic metastases ( 7 ) . the 5-yr survival rate is approximately 50% , and the 10-yr survival rate is only 30% ( 2,8 ) . in conclusion

neuroendocrine neoplasm of the larynx is a morphologically heterogeneous group of tumors . this unusual neoplasm includes the four different type of tumors . paraganglioma is the best - known neural origin tumor . the epithelial origin tumor is further divided based on the degree of differentiation into well , moderately , and poorly differentiated carcinoma . the diverse biological behavior of neuroendocrine neoplasm of larynx makes an accurate diagnosis of paramount importance , since treatment depends on diagnostic accuracy . the diagnosis is based primarily on light microscopy , and immunohistochemical and/or ultrastructural investigations are needed to diagnose correctly . the mainstay of treatment of moderately differentiated neuroendocrine carcinoma of the larynx is surgery . elective neck treatment should be performed considering the high likelihood of cervical lymph node metastases . the 5-yr survival rate approximates 50% , and 10-yr survival rate is only 30% .

giant cell tumor of soft tissue ( gct - st ) originally described in 1972 in 2 different series by salm and sissons is a rare entity , which is clinically and histopathologically indistinguishable from giant cell tumor of bone . gct - st is a benign tumor , which can transform into malignant form and also has potential for recurrence and rarely metastasis . we present an otherwise healthy , 53 year - old african american female who originally presented with chronic swellings of her left finger was diagnosed with giant cell tumor of the hand , which is rare disease . a 53-year - old lady presented in outpatient clinic with complains of swellings on the dorsum of her left ring finger . accordingly to the patient , she noticed swellings after motor vehicle injury two years ago , when she hit her finger against the wall ; growth was slow and gradual but rapidly increasing in size from few months recently interfering with hand movement and daily activities . on examination patient has a markedly loculated lesions on the left ring finger from the proximal interphalangeal joint to distal interphalangeal joint not adherent to bony structure and no evidence of joint effusion . an x - ray show soft tissue swelling seen adjacent to the middle phalanx of the fourth digit with no associated osseous erosion or radiopaque foreign body ( figure 1 ) . initial thought was ganglion cyst also suspected aneurismal bone cyst , chondromyxoid fibroma ( rare ) infectious cyst . laboratory work - up showed normal serum levels of calcium , phosphate and alkaline phosphatase . the patient was referred to a hand surgeon who found four nodules : the largest one was in middle of the middle phalanx and none was attached with underlying bone . pathology report showed well circumscribed , non - encapsulated and multinodular lesion , composed of round to spindle - shaped cells intimately admixed with scattered osteoclast - like multinucleated giant cells in a background of small , ovoid , mono - nuclear stromal cells , consistent with giant cell tumor of soft tissue ( figure 2 ) . histopathologically , gct - st should be separated from other tumors that show prominent giant cell component such as giant cell tumor of tendon sheath , extra skeletal osteosarcoma , non - ossifying fibroma aneurismal bone cyst . figure 2microscopic examination shows a mixture of mononuclear round to oval cells and osteoclast - like multinucleated giant cells . microscopic examination shows a mixture of mononuclear round to oval cells and osteoclast - like multinucleated giant cells . this case illustrates the detailed diagnostic evaluation and the need for high suspicion by the primary physicians to consider giant cell tumor of soft tissue as differential diagnosis for a lumps in hand because of the propensity of this tumor to be malignant and in some cases metastasize to lung , which is really catastrophic . patients should be highly encouraged to undergo surgical resection , as this often is the only modality of therapy with curative intent and/or the malignant component .

giant cell tumor of soft tissue originally described in 1972 in two different series by salm and sissons is a rare entity , which is clinically and histopathologically indistinguishable from giant cell tumor of bone . usually involve thigh , trunk , and lower extremities but rarely involve the hands . gct - st is a benign tumor , which can transform into malignant form and also has potential for recurrence and metastasis . we present an otherwise healthy , middle age female who originally presented with swellings on her left finger was diagnosed with giant cell tumor of soft tissue hand .

demyelinating disorders like multiple sclerosis ( ms ) is a common cause of neurological morbidity and mortality among the general population . rare variants of ms like balo concentric sclerosis ( bcs ) are classically considered to have a rapid progression , poor outcome , and poor response to treatment . newer diagnostic modalities like magnetic resonance spectroscopy ( mrs ) have helped in early ante - mortem diagnosis and have also shed light on the pathogenesis of the disorder , which has until now remained largely obscure . a 26-year - old male reported in august 2009 , with complaints of acute - onset of loss of speech , deviation of face toward the right , nasal regurgitation of fluids , and altered behavior in the form of irrelevant and persistent smiling or crying , for the last 13 days . a day before there was no history of fever , headache , blurring of vision , diplopia , tinnitus , vertigo , seizures , unconsciousness , weakness of limbs , or bladder bowel involvement . there was no previous history of preceding infection or vaccination few days or weeks prior to the onset of neurological symptoms . during the examination , the patient was conscious , oriented with stable vitals , but aphasic ( transient , motor ) , and left upper motor neuron type facial nerve palsy with ninth and tenth cranial nerve paralysis , in the form of an absent gag reflex . neck rigidity and kernig 's sign were absent ; bilateral fundii , pupillary reflex , visual acuity , and color vision were normal with no ophthalmoparesis . the sensory and motor system and deep tendon reflexes were normal , the plantars were bilaterally downgoing , the romberg sign was negative , and coordination was normal . there was no history of diabetes , hypertension , palpitation , breathlessness , photosensitivity , or joint pains in in past . human immunodeficiency virus ( hiv ) , anti - nuclear antibody , anti - dsdna , rheumatoid factor , and anti - phospholipid antibody were negative . differential diagnosis included confluent acute demyelinating encephalomyelitis ( adem ) and confluent lesions of ms . cerebrospinal fluid ( csf ) analysis showed a total white blood cell ( wbc ) count of 06 cells ( all lymphocytes ) , sugar 36 mg% , protein 97.5 mg% , and adenosine deaminase 7.2 iu . it was negative for oligoclonal bands or igg . t2-weighted mri sequences [ figure 1 ] and fluid - attenuated inversion recovery ( flair ) sequence images showed bilateral asymmetric hyperintense confluent lesions in the periventricular and centrum semiovale location , suggestive of a demyelinating pathology [ figure 2 ] . axial t2wi and gadolinium - enhanced scans showed characteristic concentric and laminated lesions [ figures . 3 and 4 ] . magnetic resonance spectroscopy obtained as a single voxel image at 135 ms , at the time of presentation , showed a non - specific choline peak , suggestive of a demyelinating pathology [ figure 5 ] . sagittal t2wi showing confluent hyperintense lesions in the periventricular location axial fluid - attenuated inversion recovery image showing hyperintense white matter lesions in the periventricular lesions contrast - enhanced gadolinium scan showing no enhancement . the concentric laminated pattern of the lesions can be seen axial t2wi and fluid - attenuated inversion recovery showing concentric laminated hyperintense lesions characteristic of concentric sclerosis magnetic resonance spectroscopy single voxel at 135 ms showing a non - specific choline peak the patient was put on oral prednisolone based on clinical suspicion of an acute demyelinating pathology . the decision to continue with this we started oral prednisolone 1 mg / kg for four weeks , and then tapered it over six weeks . the patient 's speech , swallowing , and facial deviation returned to almost normal during the eight days of hospital stay . the patient was normal at the three- , six- , and twelve - month follow - up , with no relapse . magnetic resonance imaging after 12 months showed reduction in size of the demyelinating plaques . on follow - up scans balo concentric sclerosis is considered a rare acute demyelinating disease of the central nervous system , of unknown etiology . some consider it as a discrete disorder and some consider it to be a variant of ms . it is more common in young males , presenting as focal neurological deficits like , hemiplegia , hemianesthesia , or coordination defects . involvement of the cerebellum , spinal cord , and optic chiasm has also been reported . the alternating lamellae of demyelination and normal myelination with perivascular lymphocytic infiltrates and absence of intrathecal igg synthesis suggests that it is a different disease entity from ms . several physiochemical , anatomical , and cytotoxic theories have been proposed , to explain the genesis of these typical lesions , the latest being the theory of tissue preconditioning , by stadelmann et al . brain biopsy is the gold standard , but with the advent of mri , many more cases are now being diagnosed ante mortem . earlier it was considered as a disease with poor prognosis , but recent cases and our case show that in a single monophasic event , complete response to therapy and survival is possible . steroids , plasma exchange , and immunosuppressive therapy have been tried , with variable responses .

the present report is a rare case of balo concentric sclerosis . most cases have either been diagnosed post mortem or have succumbed to the disease after being diagnosed ante mortem . in our case , the patient showed a dramatic response to treatment , and after a one - year follow - up , he was asymptomatic , with no relapses or residual effect of the illness .

this has encouraged many projects aimed at finding protein functions based on the detection of their relationships . genome - scale interaction discovery approaches , such as the two - hybrid system ( 15 ) and affinity purification ( 6,7 ) have suggested thousands of protein protein interactions . in silico approaches have also predicted many interactions with levels of accuracy similar to those determined experimentally ( 8) . put together , all these interactions have uncovered many aspects of protein connectivity but without critical molecular details often necessary to understand their function . another difficulty is that it is often impossible to distinguish between direct physical interactions and functional associations that may not involve direct atomic contacts between macromolecules . currently , atomic details of interactions are present in high - resolution three - dimensional ( 3d ) structures of protein complexes but this information is scarce and has been largely overlooked in large - scale studies . the database of interacting domains of known 3d structure ( 3did ) exploits structural information to provide atomic details for thousands of direct physical interactions between proteins . proteins are composed of modular elements ( domains ) that to a great extent determine their structure , function and interaction partners . we thus decided to structure our database on domains rather than full - length proteins . 3did obtains the high - resolution structures of individual proteins and complexes from the protein data bank ( pdb ) ( 9 ) . pfam ( 10 ) domains are then assigned to each individual protein and interactions between them are computed and the information stored . currently , 3did includes information on 50 700 protein chains of known 3d structure making a total of 48 426 domain domain interactions . of these , 13 482 occur between domains in the same chain ( i.e. intra - molecular ) and 34 944 between domains lying in different proteins ( i.e. inter - molecular ) . of these 411 always interact within the same polypeptide chain ( intra - molecular ) , 1765 are only seen in different chains ( inter - molecular ) , and 359 containing both intra- and inter - molecular interactions . gene ontology ( go ) ( 11 ) terms for molecular function , biological process and cellular component could be assigned to 1325 , 1122 and 480 families , respectively . the database also contains 1128 links between known structures and interactions between yeast proteins determined experimentally as defined in mips ( 12 ) . new 3d structures are incorporated weekly and major updates take place whenever a new version of pfam is released . up - to - date statistics on 3did contents can be found in the website . the standard way of accessing the database is by querying it with a particular domain . when doing so , 3did will show all domains that physically interact with our domain of interest and for which the 3d structure of the interaction is known . we computed physical interactions by requiring at least five contacts ( hydrogen bonds , electrostatic or van de waals interactions ) between the two domains , and removed those that lack a significant interface as described previously ( 13 ) . nevertheless , it is likely that 3did still contains some non - biological contacts ( e.g. from crystal packing ) , although we are working to remove them . the page will also show a list of the pdb codes for such domains and the associated functional go terms , if defined . domain interactions will also be displayed as an interactive network ( figure 1 ) , where the user can choose the depth and a color scheme based on molecular function , biological process or cellular compartment as described by go . the network also gives information on the type of contacts ( i.e. intra- or inter - molecular ) observed between the domains . the user can then select a particular interaction among all the possibilities and retrieve the specific details stored in 3did . the output page for each domain domain interaction displays a table with information concerning all the known 3d structures where this interaction is found ( figure 2 ) . the table shows the exact location of the two domains in the 3d complex and gives empirical potential scores and z - scores , which provide a measure of the number of favorable interacting residue pairs at the interface ( 13,14 ) . they generally account for interaction specificity : the higher the z - score , the more specific the interaction . finally , by clicking on the rasmol ( 15 ) icon , we will get a display of the 3d complex . the two interacting domains are colored and shown in ribbons representation with the residues participating in the interface ( i.e. making hydrogen bonds , salt bridges or van der waals contacts ) are shown in ball - and - stick ( figure 2 , top right ) . the table also contains links to our tool for plotting similarity in interactions ( simint ) ( 16 ) . simint plots structural comparisons ( irmsd ) of all instances of interactions of known 3d structure , highlighting those between the domains of interest ( figure 2 , bottom right ) . this plot provides details as to how interactions involving particular families , superfamilies and folds , as defined in the scop database ( 17 ) can vary . based on an analysis of hundreds of interactions , we suggested that two pairs of proteins do interact in a similar way if the irmsd is < 10 . we have also incorporated into 3did experimental interaction data for the yeast saccharomyces cerevisiae from mips ( figure 2 ) . for each yeast protein , we assign domains and whenever two interacting proteins contain domains also present in 3did , we suggest that the interaction will likely occur via these domains , therefore suggesting molecular details for such interaction ( e.g. which residues are involved , etc . ) . it should be noted that some interactions in mips ( i.e. those that form pull - down experiments ) link subunits in a complex that are not in physical contact and thus are not present in 3did . the user can also choose to query 3did by pasting a protein sequence . here , the web - tool will graphically display your sequence with pfam domains assigned automatically by means of blast ( 18 ) ( e - value 10 ) and links to interaction information for each domain . alternatively , the user can search for all interactions in a given structure ( figure 3 ) or query 3did directly with go or scop accession codes . 3did also offers the possibility to check whether there is a putative indirect interaction path across similar proteins of known structure . the search engine looks for all possible paths in 3did and displays those with the shortest length . this is particularly useful for large complexes , where components are known , but not the physical contacts . for example , in cytochrome c oxidase ( cox ) , we can find a path between domains cox2 and cox8 since , although they do not interact directly , both interact with cox4 ( figure 3 ) . future developments will include domain definitions from smart ( 19 ) , additional experimental interaction data and classification of interaction types ( transient , tight - complexes , etc . ) . mysql and flat files containing the entire database are available through the website for independent studies .

the database of 3d interacting domains ( 3did ) is a collection of domain domain interactions in proteins for which high - resolution three - dimensional structures are known . 3did exploits structural information to provide critical molecular details necessary for understanding how interactions occur . it also offers an overview of how similar in structure are interactions between different members of the same protein family . the database also contains gene ontology - based functional annotations and interactions between yeast proteins from large - scale interaction discovery studies . a web - based tool to query 3did is available at http://3did.embl.de .

cutaneous leiomyomas are rare benign tumors arising from smooth muscle cells . according to their site of origin these lesions can be arranged in diffuse ( disseminated ) , blaschkoid , or segmental ( zosteriform ) patterns . cutaneous leiomyomas are rare benign tumors arising from smooth muscle cells . according to their site of origin piloleiomyomas are the most common type among cutaneous leiomyomas and are often multiple than solitary . these lesions can be arranged in diffuse ( disseminated ) , blaschkoid or segmental ( zosteriform ) patterns . piloleiomyomas are transmitted as an autosomal - dominant trait and may be associated with uterine leiomyomas and aggressive renal carcinoma . a 30-year - old unmarried female presented to us with 15 years history of painful papules and nodules only on right half of the body . these lesions initially appeared on the right upper limb and the shoulder but subsequently developed over the trunk , gluteal region , and the thigh of the same side . each lesion started as a papule , which gradually increased in size to form a nodule . she also gave history of pain associated with these lesions , especially on exposure to cold and touch . menstrual history did not reveal any abnormality , and there were no known family members with cutaneous leiomyomas or uterine fibroids . cutaneous examination revealed multiple tender erythematous papules and nodules [ figure 1 ] , varying in size from 0.5 cm to 2 cm , distributed in segmental pattern over the upper limb , trunk , and thigh on the right side of the body with sharp limitation in the midline [ figure 2 ] . multiple piloleiomyomas on the right arm and shoulder multiple piloleiomyomas distributed along 5 cervical , 6 dorsal , and 1 sacral segments of right half of the body based on history and cutaneous examination findings , we considered the differential diagnosis of leiomyomas , angiolipomas , eccrine spiradenomas , and neurofibromas . routine hematological investigations , blood urea , serum creatinine , and ultrasound examination of the abdomen were within normal limits . histopathological examination of skin biopsies taken from the arm , trunk , and thigh showed bundles of spindle - shaped cells arranged in an interlacing and whorled pattern with elongated nuclei having rounded ends confirming the diagnosis of piloleiomyoma [ figure 3 ] . patient was started on nifedipine 10 mg thrice - daily with significant symptomatic improvement in 3 months . cutaneous leiomyomas are rare benign tumors arising from smooth muscle cells . according to their site of origin , they can be classified into 3 types : ( i ) those derived from the arrector pili muscle of hair follicles ( piloleiomyomas ) , ( ii ) those originating from the vascular smooth muscle ( angioleiomyomas ) , and ( iii ) those arising from the smooth muscle of genital skin ( dartoic leiomyomas ) . these are transmitted as an autosomal - dominant trait and may be associated with uterine leiomyomas ( multiple cutaneous and uterine leiomyomatosis , also known as reed 's syndrome or mcul ) and aggressive renal carcinoma ( hereditary leiomyomatosis and renal cell carcinoma or hlrcc ) . recently , a loss of function mutation in the gene encoding fumarate hydratase on chromosome 1q42.3 - 43 has been shown to predispose individuals to mcul and hlrcc . piloleiomyomas usually present as small , red - brown , firm papules on the extremities or trunk of young adults . individual lesions range in size from few millimeters to 1 cm that are fixed to the skin and are freely movable over underlying deeper structures . patients with piloleiomyoma often have pain that may be spontaneous or secondary to cold , pressure , or emotion . pressure of the tumor on local nerve fibers and contraction of the smooth muscle fibers are the possible explanation for this phenomenon . these lesions can be arranged in diffuse ( disseminated ) , blaschkoid , or segmental ( zosteriform ) patterns . type i segmental reflects heterozygosity of a post - zygotic mutation , leading to segmental skin lesions comparable to non - mosaic phenotype , whereas type 2 segmental reflects post - zygotic mutational event in a heterozygous embryo with subsequent loss of heterozygosity , resulting in pronounced pattern of the segmental lesions superimposed on the ordinary phenotype of the underlying disease . the tumor is composed of bundles of smooth muscles arranged in an interlacing and sometimes whorled pattern . surgical excision is often considered if the lesions are few in number . however , in case of extensive lesions , various pharmacological options like nifedipine , doxazocine , gabapentine , and topical 9% hyoscine hydrobromide have been used to alleviate the pain associated with these tumors . in conclusion , we present a case of unilateral multi - segmental leiomyomas . though segmental distribution of leiomyoma is common , multi - segmental variant has not been reported so far , and pubmed search between 1966 and 2011 could not locate any case reports of piloleiomyomas showing unilateral and multi - segmental distribution . hence , the case is being reported for its rare presentation and the need for long - term follow - up in view of its association with aggressive renal carcinoma . however multi - segmental variant has not been reported so far , and pubmed search between 1966 and 2011 could not locate any case reports of piloleiomyomas showing unilateral and multi - segmental distribution .

a 30-year - old female presented to us with multiple tender erythematous papules and nodules . these lesions showed multi - segmental distribution along 5th cervical , 6th dorsal , and 1st sacral segments of right half of the body . histopathological examination confirmed the clinical diagnosis of leiomyoma . patient was started on nifedipine 10 mg thrice - daily with significant symptomatic improvement in 3 months . though segmental distribution of leiomyoma is common , unilateral multi - segmental distribution has not been so far reported in the literature . hence , the case is being reported for its rare presentation and the need for long - term follow - up in view of its association with aggressive renal carcinoma .

nosocomial pneumonia is the most commonly acquired infection in hospitalized patients , particularly those on mechanical ventilators in the intensive care unit . the impact of this infection is dramatic , increasing mortality , length of stay , and utilization of resources such as mechanical ventilation and antibiotic therapy . nosocomial pneumonia adds as much as $ 20,000 to hospital costs per episode , and can increase hospital length of stay by as much as 14 days . in spite of aggressive , accurate therapy , some patients die as a direct result of pneumonia , and it is difficult to put a cost value on this endpoint . patients who die rapidly generally incur little excess cost of care , while those who die after a prolonged hospital stay may require therapies that lead to huge cost excesses . in terms of costs , as in other areas , prevention of nosocomial pneumonia may be better than effective treatment and cure . another factor has recently added to the cost impact of nosocomial pneumonia , namely the increasing frequency of infection caused by antibiotic - resistant organisms . the impact of pneumonia can be even more dramatic if it involves a multi - resistant gram - positive organism ( such as methicillin - resistant staphylococcus aureus ) or a gram - negative organism ( such as pseudomonas aeruginosa or acinetobacter spp . ) . first , since patients who acquire these organisms are already very ill and the availability of effective therapy is limited , pneumonia due to resistant organisms can lead to a higher mortality and length of stay than pneumonia due to antibiotic - sensitive organisms . this may partly be the result of the natural history of infection with such organisms , with some organisms being more virulent than others , as well as a result of the fact that patients infected with such organisms are more likely to receive ' inadequate ' initial empiric antibiotic therapy . the effective antibiotics may be expensive and may need to be given for a prolonged duration , often in combination with multiple other agents . management may cost more because of the need for private isolation rooms , more staff , and more equipment , such as gowns , gloves , masks , and sterile medical equipment . finally , the complications of infection ( such as delayed return to normal functional status , shock and renal failure ) and the need for tracheostomy may be greater in patients infected with resistant organisms than in those infected with sensitive organisms . for example , controversy exists about whether to diagnose ventilator - associated pneumonia ( vap ) by invasive methods or by clinical assessment . one argument in favor of invasive methods is that clinical diagnosis is too sensitive , and that some patients receive antibiotic therapy unnecessarily , with predictable impact on both costs and the emergence of resistant organisms . one prospective , randomized controlled trial in fact showed that patients managed with bronchoscopic diagnosis had more antibiotic - free days than patients managed clinically , without an adverse impact on outcomes , and this certainly could add to cost effectiveness . while using fewer unnecessary antibiotics is a desirable endpoint , it may also be achieved by careful and serial clinical evaluation , using the clinical pulmonary infection score . in one study , serial measurement of the clinical pulmonary infection score , identifying patients who did not have progressive clinical worsening , allowed investigators to shorten duration of therapy in some patients , reducing emergent antibiotic resistance . these studies clearly document the need for recognizing that some patients are currently receiving therapy when it is not needed and are being treated for too long . the need to use antibiotics more selectively must , however , be weighed against the observation that inadequate initial empiric therapy of vap is the most important determinant of excess mortality . one way to use antibiotics more accurately is to have guidelines for usage that have been adapted to local microbiologic patterns , recognizing that each intensive care unit has its own unique patterns of antibiotic resistance . in addition , if these resistance patterns are documented and used as a basis for antibiotic selection , the accuracy and cost effectiveness of therapy can be improved . a responsible and cost effective approach to vap may thus require the use of broad spectrum empiric therapy , designed to avoid inadequate coverage of multi - resistant pathogens , combined with a ' de - escalation of therapy ' in selected patients once culture data and clinical evolution information become available . perhaps the most cost effective way to manage vap is by prevention and , while there are many proposed strategies , the simplest will probably be the most effective . these strategies include : positioning patients semi - erectly , not supine , using endotracheal tubes that allow for subglottic secretion drainage ; maintaining endotracheal tube cuff pressures at levels that prevent aspiration of pooled secretions above them ; monitoring for excess gastric residuals that can lead to aspiration ; feeding into the small bowel whenever possible to avoid aspiration and bacterial translocation ; careful handling of ventilator circuits to avoid washing condensate back to patients ; and the use of non - invasive ventilation rather than intubation whenever possible . in addition , several antibiotic interventions may be effective , such as giving 24 hours of therapy to patients with witnessed aspiration , rotation of empiric regimens , and using selective digestive decontamination in carefully selected populations . in the future , our evaluation of new therapeutic approaches to nosocomial pneumonia will clearly focus on a measurement of improved outcomes , and not just on assessment of the microbiologic and clinical response to antibiotic therapy . while mortality is the ultimate endpoint to prove the value of new approaches , cost effectiveness is also an important goal .

ventilator - associated pneumonia is a common illness in intensive care unit patients . the costs of management are increased when infection involves resistant organisms , as well as unnecessary and prolonged therapy . efforts at accurate diagnosis , therapy and prevention can reduce the cost impact of this illness .

acute pancreatitis is characterized by the onset of parenchymal and peripancreatic fat necrosis with associated inflammation in a previously healthy individual . acute pancreatitis should be suspected in patients with acute severe abdominal pain and can be classified based on severity . the atlanta classification divides acute pancreatitis into two groups : interstitial edematous acute pancreatitis and necrotizing acute pancreatitis . the first category is characterized by pancreatic parenchymal and peripancreatic inflammation without necrosis , while the latter category involves inflammation and some degree of necrosis . the diagnosis of drug - induced acute pancreatitis first requires a diagnosis of acute pancreatitis . elevations in several biomarkers are indicative of pancreatitis , including serum lipase and amylase that are secreted in bulk by pancreatic acinar cells and thus are most commonly measured . other laboratory tests with diagnostic implications include serum trypsinogen , pancreatic proteases , c - reactive protein , interleukin-6 and interleukin-8 . the next step in diagnosing drug - induced pancreatitis requires ruling out more common etiologies such as gallstone pancreatitis and ethanol - induced acute pancreatitis . the history should focus on previous symptoms and any record of gallstones , ethanol abuse , hypercalcemia , hypertriglyceridemia and trauma . serum amylase , lipase , triglyceride level , calcium level and liver function tests should be ordered . abdominal and endoscopic ultrasounds should be performed to evaluate for gallstones and other obstructive possibilities such as tumors of the pancreas head . orlistat is a pancreatic lipase inhibitor which is used to treat obesity . due to the increasing prevalence of obesity the indications of orlistat are body mass index ( bmi ) > 30 without any risk factors or bmi > 27 with additional risk factors such as hypertension , hyperlipidemia or diabetes . orlistat has been reported to be associated with adverse events such as hepatic cholestasis , subacute hepatic failure and hepatic necrosis . however , placebo - controlled studies have shown no relationship with acute pancreatitis [ 4 , 5 , 6 , 7 , 8 , 9 ] . only four cases of acute pancreatitis associated with orlistat have been reported in the literature , and one of those cases did not demonstrate an increase in serum amylase [ 10 , 11 , 12 ] . we report an interesting case caused by orlistat use caught in the early stages of acute pancreatitis through imaging ; in addition , the case had significantly elevated serum amylase levels . a 54-year - old male with a history of hypertension was admitted to the emergency department with complaints of abdominal pain , nausea and vomiting lasting for 24 h. it was learned from his medical history that he had been using irbesartan for 7 years , and in addition to this drug , orlistat treatment had been started 7 days before for obesity . the obese - looking patient had a height of 1.72 m , a weight of 94 kg and a bmi of 31 . he was afebrile with a blood pressure of 140/90 mm hg and a pulse of 102 bpm . the results were : white blood cells 12,600/l , serum amylase 2,409 u / l , c - reactive protein 136 mg / l and lactate dehydrogenase 835 u / l . abdominal computed tomography revealed peripancreatic fat tissue edema and a heterogeneous appearance of the pancreas ( fig . on the third day after admission , abdominal pain , nausea and vomiting were improved . serum amylase levels were normal and the patient was told to take specific measures addressed to his obesity . alcohol use and gallstones are responsible for the development of more than 80% of acute pancreatitis cases . drug - induced acute pancreatitis has a good prognosis and can be diagnosed by exclusion . absence of gallstones , lack of a history of alcohol use with normal serum lipid and calcium levels and history of a recently started new medication support the diagnosis [ 13 , 14 ] . orlistat blocks intestinal fat absorption by inhibiting gastric and pancreatic lipase and thus can cause symptoms such as rectal pain , oily feces , frequent defecation , nausea and vomiting . all these lead to a modification of the patient 's behavior and eating habits to avoid eating fat , with the patient consequently losing weight . orlistat is metabolized in the gastrointestinal tract and its direct destructive effect is shown in intestinal villi of animal models . however , the mechanism in the development of acute pancreatitis is not known ; a possible mechanism may be direct toxicity or hypersensitivity such as in other drug - induced acute pancreatitis . we report a case of drug - induced acute pancreatitis about 1 week after initiation of orlistat . the patient in our case had a very high serum amylase level , although imaging studies showed that he was in a very early stage of edematous pancreatitis . serum amylase levels were found to be normal in a previously reported case of acute pancreatitis associated with orlistat . therefore , acute pancreatitis must be kept in mind when faced with newly developed abdominal pain in patients under orlistat treatment . in addition , imaging techniques ( such as hepatobiliary ultrasound and abdominal computed tomography ) should be requested . more attention must be paid when planning to prescribe orlistat to patients if there are risk factors for acute pancreatitis ( alcohol use , height , serum calcium and lipid levels ) .

orlistat is a pancreatic lipase inhibitor which is used to treat obesity . due to the increasing prevalence of obesity , orlistat use is thought to rise progressively . we report an interesting case caused by orlistat use caught in the early stages of acute pancreatitis through imaging ; in addition , the case had significantly elevated serum amylase levels . a 54-year - old male who had a history of orlistat treatment started 7 days before was admitted to the emergency department with complaints of abdominal pain , nausea and vomiting lasting for 24 h. abdominal computed tomography revealed peripancreatic fat tissue edema and a heterogeneous appearance of the pancreas . based on these findings , it was concluded that edematous pancreatitis was in its initial stage . orlistat is a drug that is increasingly widespread use due to obesity . more attention must be paid when planning to prescribe orlistat to patients if there are risk factors for acute pancreatitis ( alcohol use , height , serum calcium and lipid levels ) .

they rarely have a fistulous communication with the respiratory or gastrointestinal tract , and thus cystic overinflation and infection are unlikely . to our knowledge , this is the first report of infradiaphragmatic retroperitoneal els complicated with infection . a 34-yr - old male who presented with a 3-week history of epigastric discomfort and a 1-week history of fever was referred to our hospital . he had been treated with intravenous antibiotics for 1 week at the other hospital . on admission the patient 's body temperature was 37.7 and blood laboratory studies suggested an infectious condition ( wbc 15,700/l , esr 120 mm / hr , crp 63.2 mg / l , amylase 96 chest radiograph showed an elevated left hemidiaphragm and a calcified mass in the left upper abdomen and computed tomographic scanning revealed that a 16-cm , multiseptated , dumbbell - shaped , huge cystic tumor containing dense mural calcifications was located in the medial aspect to the left lobe of the liver and spleen , and in the upper anterior aspect of the left kidney . the mass extended to the pancreatic tail and its apex was abutting the heart ( fig . 1 ) . on the following day , 850 ml of thick yellowish pus was drained by sonography - guided fine needle aspiration for the purpose of infection control and diagnosis , but no microscopic organisms were found in repeated culture studies . on the 8th day of admission , magnetic resonance imaging showed a much reduced cyst size , and patient 's body temperature was normalized but blood laboratory data revealed still infectious condition ( wbc 9,700/l , esr 120 mm / hr , crp 44.7 the clinical diagnosis was of a subphrenic abscess or pancreatic pseudocyst and surgical treatment was needed . on the 10th day , the procedure was performed with the patient in the left semi - lateral position with a small roll placed posterior to elevate the left side . a thoracoabdominal incision was made through the 11th intercostal space and a careful inspection of the pleural and retroperitoneal spaces was performed . no abnormal findings were revealed in the pleural space but a cystic mass with adhesion to the surrounding organs was found in the retroperitoneal space . calcified materials and thick yellowish pus careful dissection of the adhesions between the cyst and the surrounding structures was performed and most of these pathologic lesions were removed but a severe adhesive lesion between the aorta and diaphragm beneath the heart could be not removed . and histopathologically , the cyst was lined by ciliated pseudostratified columnar epithelium and surfactants secreted by type ii pneumocytes were observed by special staining ( fig . 3 ) . in the cystic contents , many wbc and necrotic materials were found but there were no microorganisms in culture study . the patient was discharged 10 days after the operation and the remnant mass had nearly disappeared at a chest radiograph obtained 3 months later . the etiology of infradiaphragmatic extralobar pulmonary sequestration has been suggested to be caused by the trapping of sequestered tissue within the infradiaphragmatic space just before pleuroperitoneal membrane closure between gestation weeks 5 and 8 ( 1 ) . infradiaphragmatic els is extremely uncommon with an estimated incidence of 2 - 5% of pulmonary sequestration , and of 10 - 15% for els below the diaphragm ( 2 ) . it is most frequently seen in the first 6 months of life , but is found incidentally , though rarely , in older children and adults ( 3 ) . grossly , els is usually a single pyramidal to round or oval lesion , ranging from 0.5 - 15 cm in largest diameter . it is covered by a smooth to finely wrinkled pleura , and may be adherent to adjacent structures if previously infected ( 3 ) . the arterial supply in 80% of esl cases comes directly from the thoracic or abdominal aortas ; around 15% receive blood from another systemic artery ( celiac , renal artery ) and 5% from the pulmonary artery , and venous drainage is predominantly into the systemic circulation , though about 25% drain completely or partially via the pulmonary veins ( 4 ) . in most cases the sequestration is close to the diaphragm in the left suprarenal area , and is associated with other congenital malformations in approximately 50% of cases . diaphragmatic hernia , pericardial defects , pectus excavatum , and congenital heart disease are the most frequently reported associated anomalies ( 5 ) . most els are asymptomatic . however , the lack of communication between an els and the tracheobronchial tree results in fluid accumulation in sequestered tissue , which results in a large size and extrinsic compression . they rarely have a fistulous communication with the respiratory or gastrointestinal tract , and thus cystic overinflation and infection are unlikely . to our knowledge , this is the first report of infradiaphragmatic retroperitoneal els accompanied with infection , but we were unable to find any fistulous tract to the respiratory or gastrointestinal tract and any infection source . spontaneous regression has been reported in patients with intralobar or extralobar intrathoracic sequestration ( 7 ) and several hypotheses have been suggested to explain spontaneous involution of the sequestered lung . progressive fibrosis of dysplastic tissue , or thrombosis and fibrosis of the feeding vessel leading to progressive infarction of the abnormal lung would seem to be the most feasible ( 7 ) . the treatment of infradiaphragmatic els is controversial , however , operative resection is still the mainstay of treatment . removal allows confirmation of diagnosis and reassures that a neuroblastoma or a cystic adenomatoid malformation is not being left untreated . resection also eliminates any risk of malignant transformation , which has been reported in other congenital cystic lung lesions ( 8) . in addition , exploration allows the opportunity to address associated anomalies , such as , congenital diaphragmatic hernias . in summary , we describe the first case of an infected infradiaphragmatic retroperitoneal els , which occurred in a 32-yr - old man , and which presented with epigastric discomfort and fever . we administered a staged management of the infected els and achieved an excellent clinical course .

infradiaphragmatic extralobar pulmonary sequestration is an extremely rare congenital malformation . it is more frequently diagnosed in the antenatal period due to routine ultrasonic examination of the fetus or in the first 6 months of life , though on rare occasions it is discovered incidentally in adults . a 32-yr - old man presenting with epigastric discomfort and fever was referred . computed tomographic scanning showed that a 16-cm , multiseptated , dumbbell - shaped , huge cystic tumor was located beneath the diaphragm . on the next day , 850 ml of thick yellowish pus was drained by sonography - guided fine needle aspiration for the purpose of infection control and diagnosis , but no microscopic organisms were found in repeated culture studies . surgical removal of the cyst was performed through thoracoabdominal incision and most of these pathologic lesions were removed but we could not find the feeding arteries or any fistulous tract to surrounding structures . histopathologic study revealed that it was extralobar pulmonary sequestration and culture study showed that many wbc and necrotic materials were found but there were no microorganisms in the cystic contents . we report the first case of an infected infradiaphragmatic retroperitoneal extralobar sequestration which was administered a staged management and achieved an excellent clinical course .

identification and triage of seriously ill patients visiting emergency department is very important for prioritization of care and answering parent 's queries about outcome , hospital stay and cost of treatment especially in developing countries like india where medical insurance of public is not developed yet . most of the existing scoring systems developed for intensive care unit ( icu ) patients and neonates , are not executed at admission , hence these are not useful for triage [ 15 ] . furthermore these are exhaustive and include multiple physical and laboratory variables making them cost and labor intensive and are thus difficult to implement in the emergency department . simplified guidelines for the emergency care of sick children developed by sandy g et al aimed at improving the triage and initiation of appropriate emergency treatment did not assess the outcome . measurement of vital signs is routine practice for children attending emergency department . in the present study , a simple scoring system toprs has been evolved using only physical variables to predict severity of illness and outcome in emergency department . a sample of 874 consecutive children attending the emergency department over a period of one year ( jan dec 2009 ) were included , out of which 97 patients who left against medical advice or admitted only for one day were excluded . six clinical variables were noted at the time of admission of patients to emergency department . these included temperature , oxygen saturation , pulse rate , respiratory rate , sensorium and seizures . these variables were divided into normal and abnormal using the standard sirs criteria and criteria outlined in pediatric advanced life support ( table 1 ) [ 8 , 9 ] . scoring of abnormal clinical variables normal score 0 , abnormal score 1 normal variable was given a score of zero and abnormal variable a score of one . the patients were sent and managed in the respective areas like intensive care unit and ward by the doctors and nursing staff as per standard protocols . the ethical clearance and permission from the institutional review board was obtained prior to initiation of the study . a receiver operating characteristic ( roc ) curve analysis was done to find out predictive ability of score . of the 777 children studied , 157 were neonates , 28.5% were females while 71.5% were males . the association of each of variables studied with the outcome ( discharge / death ) is shown in table 2 . temperature , oxygen saturation and respiratory rate were found to have significant effect on the outcome while pulse rate , sensorium and seizures did not affect the mortality significantly . a multiple logistic regression analysis was done to determine the magnitude of association of each variable with mortality ( table 3 ) . association of study variables with mortality weight ( regression coefficient ) for each variable : logistic regression analysis the maximum possible score for any child was found to be 6.68 . however , in this study the maximum observed score was 6 . it was observed in this study that increase in the number of abnormal variables of toprs score caused a statistically significant increase in the mortality . a mortality of 4.4% was observed in children with zero score while 80% of children having a score of 5 at admission died . a child with score of 6 had an odds ratio of 615 of dying in the hospital as compared to a child with a score of less than 1 ( table 4 ) . maximum discrimination was observed for a score of 2.5 ( sensitivity-79.6 , specificity-74.43 ) . triage is very important in the emergency department . it helps to ensure that patients are treated in order of their severity of illness and it should also be easy to use so that it can be applied at first contact with patient . one of the earliest physiological scoring systems for children was physiology stability index ( psi ) in which score was calculated from the worst of 34 values from routinely measured variables over first day of picu stay . to make it less tedious , pediatric index of mortality , on the other hand was assessed directly on admission to picu . all these scoring systems are either for icu patients or requiring extensive laboratory variables and observation . thus , these systems ca n't be used in emergency department and precious time is lost as laboratory investigations take time . emergency triage , assessment and treatment ( etat ) guidelines have been formulated by who for use in developing countries . the drawback with this system is that it requires specialized training program for doctors and other health care staff for implementation . in a study conducted by m. thompson et al , it was concluded that a combination of vital signs can be used to differentiate children with serious infections from those with less serious infections in a pediatric assessment unit . in the present study so the biochemical and other variables were excluded and the physical variables were taken based on the sirs criteria and its continuum . no special training is required for implementation and can be applied immediately when the patient comes in emergency . a total of six physical variables were studied , out of which 3 variables viz temperature , oxygen saturation and respiratory rate were having a significant effect on outcome on univariate analysis . it was observed that as the number of abnormal variables increased , the mortality also increased progressively . the predictive ability of the score was found to be 81.7% on roc curve analysis . in a study conducted by manoj gupta et al simultaneously in india and england , severity of illness was assessed using sick score , the predictive ability of the score was found to be 84.1% . maximum discrimination was seen at a score of 2.5 with sensitivity of 79.6 and specificity of 74.4 . thus , any patient presenting in emergency department with 2 or more abnormal variables at admission should be treated as serious requiring admission as there is a potential risk of death . cut off scores were not proposed in study conducted by manoj gupta et al as it required larger sample size . morley cj et al developed a baby check scoring system on the basis of 28 predefined symptoms and 47 physical signs and found it to be useful to help quantify the severity of baby 's systemic illness . however , they did not study the outcome . limitation of the study : however in the current study interpersonal variability among attending doctors may exist which is not accounted for . a simple clinically developed scoring system ' toprs ' will be useful in predicting severity of illness and also outcome at admission itself in emergency department .

objectiveto develop a simple clinical scoring system for severity of illness to help prioritize care and predict outcome in emergency department.methodsprospective hospital based observational study . out of a total of 874 children who attended emergency department in one year , 777 were included in the study . data was collected at the time of admission in emergency department . the baseline information like age , gender , etc and variables of toprs score viz temperature , oxygen saturation , pulse rate , respiratory rate , sensorium and seizures were recorded . variables were categorized as normal ( score zero ) or abnormal ( score 1 ) based on systemic inflammatory response syndrome ( sirs ) criteria and criteria mentioned in advanced pediatric life support ( apls ) and the total scores were computed for each child . the outcome ( death / discharge ) was correlated with the study variables and total score . the predictive ability of score was calculated using receiver operating characteristic ( roc ) curve analysis.findingsof the six variables , temperature , oxygen saturation and respiratory rate were found to be significantly associated with mortality . mortality increased with the increase in the number of abnormal variables . based on the regression coefficients , maximum possible score was 6.68 . the predictive ability of score was 81.7 calculated using roc curve . maximum discrimination was observed at a score of 2.5.conclusionfor triage in emergency , any patient with 2 or more abnormal variables should be closely monitored and evaluated . these patients require admission as they have a potential risk of death .

it was a prospective , non - randomized , interventional case - series study of patients with large macular holes . all patients in the study had idiopathic large macular holes as determined by bio microscopy and optical coherence tomography ( oct ) imaging . exclusion criteria were macular holes of < 700 m and macular hole due to other causes . demographic and clinical data were collected for all patients , including age , sex , best - corrected visual acuity ( bcva ) and intraocular pressure . slit - lamp bio microscopy of the anterior segment and fundus with + 90 d was also done . the diagnosis of macular hole in all patients was confirmed using spectral - domain oct . the follow - up was done at day 1 , day 7 , 1 month , 2 months and 6 months . final bcva was recorded and complete ophthalmic evaluation with oct imaging was done during all the visits . all patients underwent 23 g three - port pars plana vitrectomy with posterior vitreous detachment induction using triamcinolone acetonide . brilliant blue dye assisted ilm peeling was done and instead of completely removing the ilm , a remnant of ilm attached to the margins of the macular hole was left in place and inverted into the hole after trimming with cutter . all patients underwent 23 g three - port pars plana vitrectomy with posterior vitreous detachment induction using triamcinolone acetonide . brilliant blue dye assisted ilm peeling was done and instead of completely removing the ilm , a remnant of ilm attached to the margins of the macular hole was left in place and inverted into the hole after trimming with cutter . demographic data and variables were analyzed [ table 1 ] . there were a total of five patients . the mean minimal linear diameter of the macular holes was 811.4 m ( 728 - 995 m ) [ figs 1 , 3 , 5 ] . mean bvca pre - operatively was 1.22 log - mar units ( 1.10 - 1.22 log mar units ) . post - operatively , mean bcva was 1.10 log mar units ( 1.0 - 1.52 log mar units ) . improvement of visual acuity was registered in all patients ( 100% ) [ figs . 2 , 4 , 6 ] . there were no intraoperative or post - operative complications . demographic and clinical profile of patients pre - operative optical coherence tomography of patient one post - operative optical coherence tomography of patient one pre - operative optical coherence tomography of patient three post - operative optical coherence tomography of patient three pre - operative fundus photo of patient one post - operative fundus photo of patient one the improvement in technique and development of finer instrumentation in vitreo - retinal surgery has significantly improved the surgical outcome of macular holes in terms of anatomical and functional success . the vitrectomy for treatment of macular hole study group showed a clear benefit in closure rates and final visual acuity with surgery versus observation for stage iii and iv macular hole . the single most reliable factor affecting the surgical outcome following surgery is the size of the hole . a number of studies have established that the mld of the hole is closely related to the rate of anatomic success . also , it has been shown that the most favorable outcomes for visual recovery were associated with better initial visual acuity . among all the different techniques for macular hole surgery , the one with the most positive effect on final outcome is vitrectomy with ilm peeling , in order to release tangential forces acting on the macular hole ( mh ) . in addition to promoting hole closure , peeling of the ilm also reduces the probability of its reopening . dye assisted technique is safe and useful in visualizing the ilm , leading to the performance of successful peeling of ilm with minimal damage to the retina . brilliant blue selectively stains the ilm and can be safely used for staining the ilm . the peeled - off ilm contains mller cell fragments which can induce gliosis and helping in closure of macular hole . thus , if a segment of peeled - off ilm is left attached , it may provoke gliosis both inside the retina and on the surface of the ilm . michalewska et al . observed closure of the macular hole by a thin membrane with an appearance consistent with the ilm . our study found that the closure rate of macular hole following this technique was 100% and the functional outcome were also better . but , a larger study group and longer follow - up period is required to further evaluate this method .

we are presenting the initial results of inverted internal limiting membrane ( ilm ) flap technique for large macular hole . five eyes of five patients with large diameter macular hole ( > 700 m ) were selected . all patients underwent inverted ilm flap technique for macular hole . anatomical closure and functional success were achieved in all patients . there was no loss of best - corrected visual acuity in any of the patients . inverted ilm flap technique in macular hole surgery seems to have a better hole closure rates , especially in large diameter macular holes . larger case series is required to assess the efficacy and safety of this technique .

pityriasis rubra pilaris ( prp ) is a rare chronic inflammatory keratosis , clinically characterized by gradually developing to reddish or orange extending plaques and keratotic follicular papules . five types of prp were classified by griffith , and there are refractory cases ( particularly in type ii ) in contrast with spontaneous cures for several years as described in the literature . at the onset in infancy , we frequently hesitate to use these medications , which are etretinate , systemic corticosteroid , and biologics recommended by previous studies . an administration of high - dosage vitamin a was described in the previous textbook of dermatology ; however , it did not describe in detail the lower limits and the period . herein , we present an infantile case of prp which was hard to classify , successfully controlled with a minimal dose of systemic vitamin a in the long term . a 12-year - old male patient ( weight 40 kg ) first presented to our hospital because of the presence of reddish asymptomatic keratosis plaques with no medications in january 2008 . the patient was not taking any medications to date ( including s - retinoids , albumin , etc . ) . the plaques had appeared on the palms and plantar aspects of the feet 6 years previously . erythematous plaques and keratotic follicular papules emerged and rapidly expanded to cover the head , trunk , and extremities over the past year ( fig . histopathologically , a biopsy specimen obtained from a reddish plaque on the patient 's back showed hyperkeratosis , acanthosis , and elongation of rete ridges in the epidermis . alternating vertical and horizontal parakeratosis in the epidermis ( checkerboard appearance ) with follicular keratinization was also observed ( fig . although topical betamethasone butyrate propionate , maxacalcitol , and oral loratadine at 10 mg / day were introduced in february 2008 , the skin lesions rapidly expanded and merged into larger plaques within 2 months , eventually covering the whole trunk ( fig . although we recommended oral etretinate according to the literature at first , his family disagreed with our suggestion . one month later , we recommended to take low - dose vitamin a and started vitamin a in oil ( chocolaa ) at 10,000 units twice a day in addition to the above - mentioned agents . before and 14 days after beginning the therapy , both vitamin a levels of peripheral blood were within the normal range , and no liver or renal dysfunction were seen . approximately 2 months after starting the vitamin a , the reddish eruptions on the whole body , including those on the palms and plantar aspects of the feet , had essentially disappeared ( fig . therefore , we discontinued the vitamin a in oil , but the eruptions on the trunk gradually relapsed 2 weeks after discontinuation . since then , we have regularly followed up the patient and have prescribed the agent during rash exacerbations . most pediatric cases of prp classified as type iii by griffith generally undergo spontaneous cure between 1 and 3 years . although the present case was a suspected type iii with no family history and a juvenile onset , the 6-year history of rash on the palms and plantar aspects of the feet may have been associated with prp ; therefore , we finally could not establish a precise classification . although the possibility of spontaneous healing was not denied in the present case , we stopped the administration of vitamin a after the change in the patient 's eruption ; the rashes were worsening and expanding again in short time . soon after re - administration of the same dose , the rashes immediately improved , indicating that the amount of the vitamin a was effective for the dosing period . administration of large amounts of vitamin a for treatment of prp has been described in previous literature and textbooks [ 2 , 3 ] , but the effective amount and period of vitamin a has not been specifically described . specifically , the previous dosage was 1,000,000 units per day for 14 days and 200,000 units per day for 35 days . therefore , re - administration of the same dose was performed , and immediate efficacy was again obtained . in the present case , we made a decision to administer 10,000 units twice a day based on the recommendations for over - the - counter drug vitamin a in japan , which define the safe amount as 5,000 units per day continuously . the amount in the present case was the minimum effective dosage of vitamin a in the previous literature . these results suggested that the clinical efficacy may not be due to a supplementary effect of vitamin a , but to a pharmacological action because serum vitamin a was within the normal limits during the therapy . hereafter , as more cases become accumulated , we would expect to clarify the effective minimum dosage , optimal dosing period , and adverse effects of vitamin a therapy for pediatric prp patients .

pityriasis rubra pilaris ( prp ) is a rare chronic inflammatory keratosis that is clinically characterized by gradually developing reddish or orange extending plaques and keratotic follicular papules . in pediatric patients , we frequently hesitate to administer certain medications for treatment of prp , specifically etretinate , systemic corticosteroids , and biologics recommended by previous studies . although administration of high - dose vitamin a was described in a previous textbook of dermatology , details about the lower limits and treatment periods were not provided . we presented a pediatric case of prp that was successfully controlled with minimum dosage of systemic vitamin a in the literature . before and 14 days after beginning the therapy , both vitamin a levels of peripheral blood were within the normal range . we considered that the clinical efficacy may not be due to a supplementary effect of vitamin a , but to a pharmacological action because serum vitamin a was within the normal limits during the therapy .

primary cardiac tumours are rare with incidence ranging from 0.001 % to 0.030 % ( 1 ) . this case highlights a primary malignant cardiac tumour with an uncommon complication ( i.e. bowel infarction ) . studies have illustrated cardiac tumour embolisation risk which varies from 12 % to 45 % ( 1 ) . a 53-year - old patient presented to hospital with a history of sudden onset excruciating abdominal pain in the umbilical region . she had last opened her bowels one day prior to admission and had been passing flatus . she has reported to having had flu - like symptoms , chest tightness , cough and orthopnoea for one week prior to this admission . on examination , the patient had a chest x ray which demonstrated cardiomegaly and an abdominal x ray ( figure 1 ) . ap abdominal radiograph ; markedly distended stomach and distension of bowel loops in the right upper quadrant the patient subsequently underwent computed tomography ( figure 2 ) . it was found that the small bowel was non viable from about 80 cm distal to the duodenojejunal flexure to the mid ileum . the bowel was judged to be non viable . a subtotal colectomy and revision of jejunostomy specialist opinion on the echocardiography images was that the scans illustrated an extensive neoplasm in the left ventricle infiltrating both the myocardium and right ventricle leading to a diagnosis of sarcoma . echocardiogram showing intracardiac tumour in view of the very poor prognosis , resection of the cardiac tumour was not advised . at this point , it was decided to commence supportive treatment . reardon et al ( 2 ) found that the majority of these tumours occurred in patients in the 40 - 50 age range . prognosis is poor with median survival reported as 16.5 and 9.5 months in 2 studies which looked at 24 and 17 cases respectively ( 3,4 ) . characteristics which are common with a malignant cardiac tumour were detailed by silverberg ( 5 ) ( i.e. sarcoma ) these are as follows : ( i ) right side cardiac mass is more likely to be malignant than left sided ; ( ii ) mass originating from free wall of cardiac chamber as opposed to the septum ; ( iii ) invasion of pericardium , great vessels and mediastinum ; ( iv)presence of distant metastases ; ( v ) extension of the mass into more than one cardiac chamber ; ( vi)concomitant pericardial and /or pleural effusion ; ( vii)diameter of mass more than 5 cm ; ( viii ) tissue inhomogeneity and contrast enhancement . these features ware present in the case we present with the exemptions being points iii and iv . elbardissi et al ( 6 ) noted that of those patients who suffered embolic events , 15% were associated with malignant tumours . it was noted that the tumour types most associated with embolism were aortic valve tumours and papillary fibroelastomas . acute mesenteric ischemia is an uncommon condition with a high mortality rate quoted to be between 60 - 90% ( 7 ) . embolic causes ( as was the case with this patient ) are commonly associated with atrial fibrillation where most thrombi arise from the left atrial appendage ( 8) . the patient in this case was not found to be in atrial fibrillation . the superior mesenteric artery is most commonly affected by emboli due to its acute angle of origin from the abdominal aorta . an embolus would characteristically lodge distal to the origin of the middle colic artery ( 9 ) . there has thus far been no documentation of mesenteric ischaemia / infarction occurring as a result of embolisation from a cardiac tumour . elbardissi et al ( 6 ) reported 80 embolic events in their cohort of patients however not one patient was recorded as having an embolic event affecting the bowel . due to the significant embolic event and subsequent complications , reshma et al ( 10 ) looked at 4 cases of patients with malignant cardiac tumours who underwent resection . the outcome was poor in all these cases which are in contrast to the resection of benign cardiac masses .

we report a rare case of small bowel infarction due to superior mesenteric artery occlusion secondary to cardiac tumour embolism . to our knowledge , this has not been previously reported in the literature . this case highlights a rare case and reviews current knowledge on the subject .

we investigate polycrystalline ni films ( 550 nm thick unless otherwise stated ) thermally evaporated , or sputtered onto various substrates chosen to act as solid carbon sources : highly orientated pyrolytic graphite ( hopg ) , tetrahedral amorphous carbon ( ta - c ) , and nanocrystalline diamond . hopg(0001 ) substrates ( mikromasch , zyh grade , < 3.5 mosaic spread ) are cleaved to 0.1 mm thickness and the surfaces cleaned by mechanical exfoliation using the well - established scotch - tape method . c was deposited on to sio2(300 nm)/si substrates using a filtered cathodic vacuum arc ( fcva ) system . nanocrystalline diamond films ( 100 nm thick ) were deposited on sio2(500 nm)/si substrates using microwave plasma enhanced cvd . al2o3 ( 13 nm ) layers are deposited by atomic layer deposition using a cambridge nanotech savannah ald system with a 200 c process that uses tri[methyl]aluminium as a precursor and water as an oxidant both carried in a n2(20 sccm ) flow for 1030 cycles . for the au decorated ni catalysts , au(5 nm ) was deposited by thermal evaporation on to the exposed ni surface . the samples are annealed under vacuum in a custom - built cold - wall reactor at selected temperatures using a standard one step procedure [ < 10 mbar , 200600 c , 5 min , heated and cooled at a constant rate of 100 c min ] unless otherwise stated . in situ high - pressure xps measurements during vacuum annealing were performed at the bessy ii synchrotron at the isiss end station of the fhi - mpg . in situ xrr and ( grazing incidence ) xrd were performed during vacuum annealing at the european synchrotron radiation facility ( beamline bm20/robl , operated by the helmholtz - zentrum dresden- rossendorf ) . ex situ characterization is performed on as - grown samples using scanning electron microscopy ( sem , zeiss sigmavp , 1 kv ) or after transfer of the m-/flg films to sio2(300 nm)/si substrates using optical microscopy , and raman spectroscopy ( renishaw raman invia microscope , 532 nm excitation ) . transfer to sio2(300 nm)/si substrates is carried out using an electrolysis - based bubbling in a naoh ( 1 m ) aqueous solution to detach pmma - supported graphene from the catalyst , with the pmma subsequently removed in acetone . electrical measurements are performed at room temperature using six contact hall - geometry devices fabricated by e - beam lithography on the as - transferred mlg . cr / au contacts are evaporated on top of the mlg which is then patterned by an o2 plasma etch .

carbon diffusion barriers are introduced as a general and simple method to prevent premature carbon dissolution and thereby to significantly improve graphene formation from the catalytic transformation of solid carbon sources . a thin al2o3 barrier inserted into an amorphous - c / ni bilayer stack is demonstrated to enable growth of uniform monolayer graphene at 600 c with domain sizes exceeding 50 m , and an average raman d / g ratio of < 0.07 . a detailed growth rationale is established via in situ measurements , relevant to solid - state growth of a wide range of layered materials , as well as layer - by - layer control in these systems .

in a previous issue of critical care , welters and colleagues presented a study on the types and frequency of critical incidents in the general icu . since most relevant studies have been limited to the investigation of errors , medication - associated or not , it is important that this study had a broader perspective by aiming to cover the entirety of critical incidents . these incidents are associated with compromised care quality and patient safety , while critically ill patients can be particularly susceptible to their consequences . critical incidents are difficult to define as a whole . in a previous study , bracco and colleagues recorded them by using a list of 105 items , including complications , infections , medication errors , falls , and so on . the five - category classification used by welters and colleagues intended to group diverse items under distinct labels . however , the items under the ' administration ' category , including staffing shortages , limited bed availability , and shortcomings in patient documentation and identification , can hardly be considered as critical incidents themselves ; they rather constitute factors contributing to them . especially icu understaffing has been associated with high rates of drug administration errors , healthcare - associated infections and postoperative complications in previous studies [ 3 - 5 ] . despite their potential to negatively affect patient clinical course , most critical incidents are not followed by adverse events . according to reason 's swiss cheese model , adverse events occur when the holes in many layers of system defense line up , that is , their cause is generally multifactorial . on the other hand , adverse events are not always attributed to critical incidents and patient injury may occur during appropriate care ( for example , adverse drug events due to allergic reactions ) . in this context , therefore , determination of recurring patterns of critical incidents is expected to reveal weak points in the process of care , being thus a research priority . at the same time , identifying types of critical incidents most commonly followed by severe adverse events also seems crucial . previous studies on icu critical incidents have focused on the frequency of their types , personnel - related causes and their consequences for patients . airway - related incidents have been reported to be the most common , followed by line - related ones . human errors accounted for 55% of incidents in a study conducted in hong kong , but did not exceed 31% in a swiss study . a total of 280 critical incidents were followed by 4 deaths and major physiological change in 3.6% of them . as regards human - related incidents , 1 out of 241 was lethal , while the rest significantly prolonged icu patient stay . unfortunately , welters and colleagues did not report any contributing factors or consequences of critical incidents , while it is worth noticing that critical incidents associated with airway and disconnection / leaks were much less common than previously reported . the limited reliability of data collected through the self - report method has been previously acknowledged . as regards errors , low report rates are common , either because personnel do not become aware of the error , or due to the fear of punitive action . voluntary error reporting not only leads to significant underestimation of their overall incidence , but may also be associated with underreporting of specific error types . errors attributed to individual rather than organizational deficiencies are less likely to be reported due to self - esteem and social desirability bias . likewise , it seems plausible that not all critical incidents are equally reported ; for example , cases of equipment malfunction seem much easier to report than incorrect equipment use . in this case , regional database data can be equally affected by underreporting of specific incident types and can thus not be used to confirm the reliability or representativeness of single - center data . seeking for root causes of critical incidents and elucidating the interactions among contributing factors that lead to them are necessary for developing effective prevention strategies . attention distractions , high personnel workload , lack of drug knowledge and mathematical skills , and communication deficiencies have been reported as primary factors contributing to medication errors [ 11 - 13 ] . since critical incidents constitute a broader field than errors , many other factors are expected to favor their occurrence , such as inadequate training about equipment use , lack of equipment checks , faulty material use , decreased patient surveillance , and so on . besides addressing incident - contributing factors , future research is further recommended to establish the associations between specific contributing factors and specific critical incident types , so that targeted prevention can be applied . conduction of multicenter studies focusing on icu critical incidents is strongly recommended for two main reasons . first , because critical incidents generally have a low frequency in a single icu , their patterns can be more clearly revealed by collecting data from several units . second , the role of factors supposed to contribute to critical incidents can be more reliably confirmed by comparing data among different units - for example , in case higher critical incident rates are associated with lower staffing levels . increased reporting rates of critical incidents can only be achieved within a non - blaming climate , by acknowledging their inevitability , treating them as opportunities for improvement , and encouraging trustful communication among personnel . gathered data should then be analyzed to allow in - depth understanding of critical incident patterns and healthcare system deficiencies as contributing factors , as well as synthesized into useful knowledge by providing clinical recommendations for prevention . feedback of this knowledge to personnel through continuous education programs will guide proper redesigning of faulty systems and quality improvement efforts .

despite their difficult definition and taxonomy , it is imperative to study critical incidents in intensive care , since they may be followed by adverse events and compromised patient safety . identifying recurring patterns and factors contributing to critical incidents constitutes a prerequisite for developing effective preventive strategies . self - reporting methodology , although widely used for studying critical incidents , has been criticized in terms of reliability and may considerably underestimate both overall frequency and specific types of them . promotion of non - blaming culture , analysis of critical incident reports and development of clinical recommendations are expected to minimize critical incidents in the future .

ureteropelvic junction ( upj ) obstruction is the most common form of upper urinary tract obstruction in children . the variations in renal arterial supply are best understood when embryology of the renal vasculature is considered . multiple renal arteries have been reported to occur in approximately 30% of cases , with a preponderance on the left side . with respect to the presence of multiple renal arteries , by a study of sampaio et al . , an inferior accessory or aberrant artery was found to cross anteriorly to the upj in 6.8% of the cases . in few specimens did this inferior accessory artery pass close to the upj . therefore , the presence of an anomalous vessel crossing the upj and causing obstruction is a very rare finding . we describe a 36-year - old woman with hydronephrosis due to upj obstruction by an aberrant renal artery and review the literature in brief . a 36-year - old woman was admitted to our hospital with intermittent right flank pain for 4 years . the pain was most often experienced during the later hours of the day , especially after ingestion of large quantities of fluid . she had been treated at a local clinic in the past for urinary tract infection with right flank pain and weakness . physical examination revealed blood pressure of 110/80 mmhg and the presence of costovertebral - angle tenderness . urinalysis were within normal limits ( wbc 0 - 1/hpf , rbc 0 - 1/hpf ) . biochemical analysis revealed blood urea nitrogen level of 11.0 mg / dl and serum creatinine level of 0.8 mg / dl . kidney ultrasonogram showed a marked dilatation of the right pelvocalyceal system and right proximal ureter . excretory urogram revealed a marked right hydronephrosis with dilated calyces due to ureteropelvic junction obstruction ( figure 1 ) . computed tomography angiogram ( cta ) clearly displayed the aberrant renal artery which originated from the aorta below the normal right renal artery ( figure 2 ) . a source image of magnetic resonance angiogram ( mra ) also showed a severe hydronephrosis of the right kidney and smooth obstruction of the right ureteropelvic junction due to extrinsic compression by an aberrant renal artery which originated from the aorta , crossing anteriorly to the ureteropelvic junction ( figure 3 ) . after furosemide infusion , the delayed right kidney excretion was somewhat improved ( figure 5 ) . the patient underwent surgical exploration via an anterior approach which revealed a slightly ptotic , mobile , right kidney which was normal in size , with a marked hydronephrotic pelvis froman aberrant renal artery and vein crossing the ureteropelvic junction , proceeding to the lower pole and compressing the ureteropelvic junction against the lower pole of the kidney . a dismembered pyeloplasty was performed , with the pelvis anastomosed to the ureter in front of the aberrant renal artery . this is partly attributable to the more widespread use of angiography and other imaging modalities in recent years . some knowledge of the embryology of the renal vessels is necessary to understand the frequent anomalies that may occur . with complicated development of the kidneys , through the three stages of pronephros , mesonephros and metanephros , and the migration of the definitive kidney ( metanephros ) from the pelvic region to the region of the posterior abdominal wall ( in the lumbar area ) , the renal blood supply undergoes successive changes in its upward migration . since arterial degeneration begins at the cephalic pole of the metanephros , the segmental branch to the lower renal pole is the one most likely to remain as an accessory artery . the association between lower polar aberrant vessels and a dilated renal pelvis was appreciated and this , acting in the nature of a physical obstruction to the urine flow , seemed to provide a logical explanation for the condition . however , it has been suggested that the obstruction may result from a neuromuscular incoordination of the ureteropelvic junction and the vascular obstruction is a secondary rather than a primary event . however , the work of johnson who studied the manometric pressures in such cases , and the electron microscopic evidence presented by notley appear to favor mechanical obstruction . the symptom of vascular ureteropelvic junction obstruction may include colicky mid - abdominal pain , nausea and vomiting . however , our patient did not present such symptoms or signs , except an abdominal pain . older modalities , such as intravenous urography and angiography , have essentially been replaced by endoluminal ultrasonography and cta . a significant advantage of the technique is that it can quantify the number and location of vessels and aid in directing an incision away from vessels . the image can be reconstructed three - dimensionally in longitudinal fashion , providing accurate information about vessels as small as 1 mm in diameter . mr imaging , including mr urography and angiography , is an effective diagnostic method to evaluate various renal diseases . mr angiography can rapidly and accurately depict renovascular diseases without using contrast medium and ionizing radiation . a source image of mra shows renal parenchyme as well as a dilated pelvocalyceal system . in the present case , the source image of mra clearly displayed the relationship between hydronephrosis and an aberrant renal artery . on the other hand , the number , location , morphology and size of the aberrant renal vessels were accurately depicted by cta . therefore , cta and mra are considered to be more non - invasive and more powerful diagnostic methods to evaluate an aberrant renal artery than conventional angiography or ct . currently , the most widely accepted surgical procedure is dismembered pyeloplasty , with the anastomosis performed anterior to the obstructing vessel .

ureteropelvic junction obstruction is usually intrinsic and is most common in children . aberrant renal arteries are present in about 30% of individuals . aberrant renal arteries to the inferior pole cross anteriorly to the ureter and may cause hydronephrosis . to the best of our knowledge , although there are some papers about aberrant renal arteries producing ureteropelvic junction obstruction , there is no report of a case which is diagnosed by the new modalities , such as computed tomography angiogram ( cta ) or magnetic resonance angiogram ( mra ) . we describe a 36-year - old woman with right hydronephrosis . kidney ultrasonogram and excretory urogram revealed right hydronephrosis . cta and mra clearly displayed an aberrant renal artery and hydronephrosis . the patient underwent surgical exploration . for the evaluation of hydronephrosis by an aberrant renal artery , use of cta and mra is advocated .

intestinal intussusception is relatively common in children , whereas in adults it is a rare clinical entity , which occurs most often secondary to a defined pathologic abnormality . although surgical resection is recommended , there is still no consensus regarding optimal management of adult intussusception caused by intestinal cancer . considering the theoretical risk of perforation , which could cause seeding of tumor cells and the release of microorganisms into the intraabdominal cavity however , less invasive management may be indicated and laparoscopy appears to be an attractive alternative to laparotomy for selected patients [ 5 , 6 ] . we describe how we performed an emergency laparotomy for adult colonic intussusception caused by sigmoid colon cancer . the successful reduction allowed us to treat the extensive intussusception with a more limited anterior resection instead of en bloc wide abdominoperineal resection . a 47-year - old woman was admitted to our emergency department with sudden and severe abdominal cramping pain after suffering repeated episodes of colicky and intermittent abdominal pain for about 1 week . on physical examination , the results of laboratory investigations were normal including tumor markers of carcinoembryonic antigen and ca19 - 9 . plain abdominal radiography showed a distended colon and digital rectal examination revealed a protuberant mass - like lesion with a smooth surface . 1 ) , sigmoid - rectum intusussception caused by sigmoid colon cancer was diagnosed . at surgery , the sigmoid colon was found to be intussuscepted into the rectum very close to the anus , making reduction difficult . after dividing the peritoneum , the surgeon inserted his hands below the peritoneal reflection along the rectum and pushed the intussusception back from the distal to the proximal rectum using a milking action ( fig . the rectum was divided 5 cm from the peritoneal reflection using a stapler , and the sigmoid colon was divided 10 cm proximal from the intussusception . we removed the intussuscepted part of the colon as well as the rectum , intermediate lymph nodes , and regional lymph nodes , and performed an anterior resection . histological examination revealed well - differentiated adenocarcinoma with invasion of the muscularis propriae ( fig . the lymph nodes were negative for cancer cells . at present , three year after surgery , she is free of symptoms and she has had an uneventful course . intussusception is a major cause of intestinal obstruction in children , but it is relatively unusual in adults . adult intussusception accounts for only 1% of all bowel obstructions , 5% of all intussusceptions , and 0.0003 - 0.020% of all hospital admissions . few general surgeons encounter more than one or two adult patients with colon intussusception during their careers , and most cases are undiagnosed before laparotomy . intussusception of the sigmoid colon is often misdiagnosed as a large polyp or rectal prolapse . however , a delay in diagnosis could result in death , so surgeons must be aware of the possibility of this type of intussusception if they find an unusual rectal tumor in a patient with intestinal obstruction . our patient presented with sudden and severe abdominal pain , after a short history of repeated episodes of colicky and intermittent abdominal pain . although abdominal pain is the most common symptom , colonic intussusception can also manifest as a variety of acute , intermittent or chronic symptoms , making its preoperative diagnosis difficult . ultrasonography has been used to evaluate suspected intussusception and findings include the target and doughnut signs on the transverse view and the pseudokidney sign on the longitudinal view . the major limitation of ultrasonography in evaluating acute intestinal obstruction is the presence of air in the bowel , which results in poor transmission and difficulties in interpreting the image . the characteristic ct findings of intussusception include an early target mass with enveloped , eccentrically located areas of low density . the characteristic appearance of intussusception on barium enema is a cup - shaped filling defect with a spiral or coil - spring appearance . the ct findings proved helpful in establishing the preoperative diagnosis in our patient . for patients with intussusception and an inflamed , ischemic or friable bowel wall , it is advisable not to attempt operative reduction , but to proceed with resection . given the likelihood of malignancy , most cases of colo - colonic intussusception should be resected en bloc without reduction , which should be avoided because it may result in the spread of malignant cells [ 2 , 4 ] . even when a benign tumor is suspected before surgery , careful manipulation is mandatory to avoid perforating the strangulated bowel with poor stability . according to nagorney et al . lynn and agrez reported a case of sigmoid colon intussusception in whom the rectum was opened circumferentially with diathermy at the point of the intussusception , and the intussuscepted sigmoid colon was delivered out of the rectum through the anus . however , this procedure would cause contamination of the abdominal cavity . in our case , the peritoneal incision was clean and allowed us to deliver the sigmoid colon out of the rectum , whereby abdominoperineal resection was avoided [ 3 , 4 ] . laparoscopic surgery is now widely used for the resection of benign and malignant gastrointestinal tumors ; however , its application for intussusception is still controversial . reported that a laparoscopic approach is safe and effective for most cases of small bowel obstruction and recommended its use as the first - line treatment . chiu et al . described the successful laparoscopic resection of ileocolic intussusception caused by primary ileal lymphoma . the usefulness of laparoscopic surgery in emergency situations , particularly for non - decompressed intestinal obstruction , remains controversial because adequate intraperitoneal visualization is almost impossible in such cases . in our case , the small and large bowel were so dilated that laparoscopic manipulation would have been difficult . the choice of a laparoscopic or open approach depends on the clinical condition of the patient , the location and extent of the intussusception , the possibility of underlying disease , and whether the surgeon has sufficient laparoscopic expertise .

adult intussusception is rare and most often associated with cancer . we report a case of intussuscepted sigmoid colon into the rectum protruding from the anus of a 47-year - old woman . the cause of the intussusception was sigmoid colon cancer . we removed the intussuscepted part of the sigmoid colon as well as the rectum and regional lymph nodes . the patient recovered uneventfully and there has been no evidence of recurrence of the cancer .

spinal deformity is the most common musculoskeletal manifestation in neurofibromatosis type i or peripheral neurofibromatosis with the incidence ranging from 10 to 60% . spinal deformities in patients affected by neurofibromatosis have been divided into dystrophic and nondystrophic forms . nondystrophic deformities behave similar to idiopathic scoliosis , but a close follow - up is firmly required because dystrophic changes may develop with time . this ability of a spinal deformity to transform by acquiring dystrophic features is called modulation , that has been reported to occur in 81% of children who present spinal deformity before age seven and 25% of those who are diagnosed after age seven . dystrophic features are characterized by a rapid and relentless progression and conservative treatment is usually ineffective [ 2 , 3 ] . common features of dystrophic deformities are represented by short thoracic curve with severe apical rotation , severe kyphosis , vertebral scalloping , pencilling of the ribs , foraminal enlargement , widening of the spinal canal , spindled transverse processes , defective pedicles , and presence of paravertebral tumors . spinal cord compression with paraplegia or paraparesis is uncommon in patients affected by dystrophic deformities and it was described as caused by severe kyphosis with vertebral subluxation , neurofibroma protruding through the foramina and ribs penetration into the spinal canal . in this paper , we report a rare case of spastic paraparesis due to spinal cord compression caused by rib penetration in the spinal canal of a child with dystrophic deformity that was treated by posterior and anterior spinal arthrodesis . the patient is a 14-year - old boy affected by type i neurofibromatosis and kyphoscoliosis . he was treated with milwaukee brace since the age of ten . at the age of 13 he began to suffer from weakness of the lower limbs and exhibited progressive difficulty on walking about . the radiological investigation confirmed the presence of a double thoracic kyphoscoliosis . the thoracic kyphosis measured 120 with the apex at the level of t5t6 ( fig . the magnetic resonance imaging showed a noticeable segmentary cord compression at the level of t5t6 and excluded the presence of intraspinal tumours ( fig . the a p ( a ) and lateral ( b ) radiographs show the severe spinal deformiyfig . 2a preoperative mri evidenced cord compression at the level of t5t6 and excluded the presence of intraspinal tumours . b a careful examination of mri permits to identify the rib displacement into the spinal canal ( white arrow ) a 14-year - old child with neurofibromatous kyphoscoliosis and worsening paraparesis . the a p ( a ) and lateral ( b ) radiographs show the severe spinal deformiy a preoperative mri evidenced cord compression at the level of t5t6 and excluded the presence of intraspinal tumours . b a careful examination of mri permits to identify the rib displacement into the spinal canal ( white arrow ) we performed surgical correction and instrumented posterior arthrodesis ( t1l1 ) using abundant bone graft . the postoperative period was regular without any neurological complication and patient was released from the hospital on the ninth postoperative day . a body cast was applied to contain any movement for a period of 2 months , during which he had complete neurological recovery . ten days later the patient complained of lower limbs weakness and he rapidly exhibited paraparesis . he was then admitted in the emergency room and x - rays showed the right position of spinal instrumentation . the ct scan confirmed that instrumentation as well as the anterior rib bone graft was perfectly inserted . nevertheless , we observed a significant narrowing of the vertebral canal and a vertebral - rib malformation at the apex of the kyphosis ( fig . the three - dimension ct scan evidenced the head of the fifth rib penetrating the vertebral canal and cord compression ( fig . three days after we observed a noticeable improvement of neurological state and a complete neurological recovery then followed . the patient worn body casts and a milwaukee brace till 9 months after surgery . at last control , 2 years after surgery , the patient was able to walk without any limitation . 3a the ct scan showed the fifth rib penetration into the enlarged intervertebral foramina ( black arrow ) . b the 3d ct scan confirmed the rib displacement into the spinal canal ( white arrow ) a the ct scan showed the fifth rib penetration into the enlarged intervertebral foramina ( black arrow ) . b the 3d ct scan confirmed the rib displacement into the spinal canal ( white arrow ) the most common pattern of neurofibromatous dystrophic deformities is represented by a single short thoracic curve and abnormal kyphosis or lordosis , characterized by rapid progression , that usually develops despite the appropriate conservative treatment . neurological deficits may be a consequence of severe kyphosis with vertebral subluxation , cord compression by neurofibroma protruding through the foramina and ribs penetration into the spinal canal . rib displacement into the spinal canal is an uncommon cause of cord compression and , to our knowledge , only few cases have been previously described with a variable involvement of the neurological functions [ 412 ] . the higher rate of rib displacement seems to be observed at the apex of the curves , where maximal rotation of vertebral bodies is present [ 10 , 12 ] . the present case report appears to be noteworthy because a complete neurological recovery was firstly obtained by posterior instrumented arthrodesis , regardless of the rib displacement into the spinal canal , that was not evidenced by preoperative radiological evaluation . actually , after ct scan assessment revealed intraforaminal rib displacement causing cord compression , a careful re - evaluation of pre - operative mri permitted us to evidence this complication ( fig . furthermore , the period that followed the posterior instrumented arthodesis did not raise any suspect about the abnormal position of the fifth rib because of the absence of neurological signs or symptoms . finally , lower limbs paraparesis appeared 17 days after anterior fusion without any promoting factor . as evidenced by all previous reported cases , rib displacement into the spinal canal may have different patterns of clinical presentation [ 412 ] . it may be of acute or insidious onset [ 5 , 7 ] and surgical treatment does not seem to be related with the occurrence of cord compression . although rib displacement into the spinal canal represents an infrequent complication of neurofibromatous spinal deformities , it must be excluded during preoperative radiological evaluation , even in the absence of neurological deficits . in fact , the presence of a rib displacement would require the surgical resection of the rib in addition to the spinal arthrodesis . to this purpose , a pre - operative study with the use of radiographs and mri scan is recommended in order to identify the abnormality . even if mri does not seem to be specific , it may raise concerns of the lesion , by a careful observation of axial and sagittal images of thoracic spine , with a particular attention in the examination at the apex of the curve . at last , a guided ct scan permits to confirm the presence of rib displacement into the spinal canal .

rib displacement into the spinal canal is a rare cause of paraplegia or paraparesis in patients affected by neurofibromatous scoliosis . we describe a case of paraparesis in a 14-year - old child affected by neurofibromatous dystrophic kyphoscoliosis , treated with combined posterior and anterior spinal arthrodesis . seventeen days after the surgical treatment the patient developed clinical signs and symptoms of paraparesis . a ct scan showed the head of the fifth rib protruding into the spinal canal with cord compression . rib resection and posterior cord decompression were carried out following complete neurological recovery .

decompressive craniectomy ( dc ) is a straightforward procedure that for more than a century has been widely used to treat medically refractory intracranial hypertension of patients with severe traumatic brain injury ( tbi ) . although a series of clinical studies demonstrated that the procedure is the one of the most effective treatments in reducing intracranial pressure ( icp ) , no large prospective randomized controlled trial ( rct ) had investigated the relation between successful or sustained reduction of increased icp and functional out - comes after dc . an updated cochrane review published in 2009 identified only one prospective randomized clinical trial ( n = 27 participants ) that evaluated the effect of dc in severe tbi . the same year , a small ( n = 74 patients ) rct that was published by qiu and colleagues indicated the beneficial effects of dc in patients with acute post - traumatic brain swelling . in march of this year , a multicenter rct by cooper and colleagues was published in the new england journal of medicine . before this multicenter rct , this multicenter rct enrolled 155 adults with severe non - penetrating tbi and medically refractory intracranial hypertension from december 2002 through april 2010 but excluded patients with mass lesions . the results showed that , although dc can immediately and constantly reduce icp ( mean icp of 14.4 mm hg versus 19.1 mm hg ; p < 0.001 ) , the craniectomy group that received bifrontotemporoparietal dc ( n = 73 ) may be associated with a worse functional out - come than the standard - care group ( n = 82 ) ( odds ratio of 1.84 and 95% confidence interval of 1.05 to 3.24 ; p = 0.03 ) . as this trial is well planned and of high quality , the unexpected result is meaningful and should be considered a reference for an evidence - based guideline . however , the evidence of the study is insufficient . second , the thresholds for defining medically refractory intracranial hypertension ( icp of greater than 20 mm hg for more than 15 minutes within a 1-hour period after first - tier interventions ) are not what many physicians would consider refractory . third , in almost 3,500 potentially eligible patients , only 155 patients were enrolled ( patients with a cerebral mass lesion were excluded ) . therefore , the study can not be generalized to all patients with severe non - penetrating brain injury . fourth , after random assignment , more patients in the dc group had fixed and dilated pupils than patients in the medical therapy group ( no reactivity of bilateral pupils : 27% versus 12% ) , and this should be considered a potential risk of bias . lastly , 15 patients ( 18% ) in the standard - care group underwent delayed dc as a lifesaving intervention . although the investigators used intention - to - treat analysis , the bias introduced by the compassionate use of dc in the standard - care group should not be overlooked . for these reasons , total disapproval of the effect of dc in severe tbi by some authors is inappropriate . additional multicenter rcts are necessary to provide further conclusions on the efficacy of this procedure . in 2006 , an international multicenter rct comparing dc with medical management for refractory raised icp was sponsored by the university of cambridge . this rescueicp ( randomized evaluation of surgery with craniectomy for uncontrollable elevation of intracranial pressure ) study planned to recruit 650 patients with refractory icp after tbi ( 50 for the pilot phase and 600 for the main study ) in an attempt to provide class i evidence on the role of surgical decompression in the treatment of raised icp after severe tbi . recently , an updated protocol revealed that the rescueicp trial had recruited over 280 patients from more than 40 centers in 17 countries . we anxiously await the results of this international multicenter rct and hope that they will enhance the evidence to guide the treatment of severe tbi . dc : decompressive craniectomy ; icp : intracranial pressure ; rct : randomized controlled trial ; rescueicp : randomized evaluation of surgery with craniectomy for uncontrollable elevation of intracranial pressure ; tbi : traumatic brain injury .

recently , a multicenter randomized controlled trial ( rct ) by cooper and colleagues indicated that decompressive craniectomy ( dc ) may be associated with a worse functional outcome in patients with diffuse traumatic brain injury ( tbi ) , although dc can immediately and constantly reduce intracranial pressure ( icp ) . as this trial is well planned and of high quality , the unexpected result is meaningful . however , the evidence of the study is insufficient and the effect of dc in severe tbi is still uncertain . additional multicenter rcts are necessary to provide class i evidence on the role of dc in the treatment of refractory raised icp after severe tbi .

they are often caused by high - energy trauma and are associated with a high mortality rate . however , such severe injuries with complex patterns are seen more commonly nowadays due to high - speed trauma caused in road traffic accidents ( rta ) on motorways . high mortality rates ( 50%77% ) have been reported for femoral shaft fractures associated with pelvic fractures and injuries to other systems . these injuries have a great impact not only on the social and economic life of individual , but also on the society . we present a rare case of bilateral unstable pelvic fractures ( acetabular and sacral fractures ) , bilateral segmental femoral shaft fracture with multiple right rib fractures and associated haemothorax . to the best of our knowledge , a 21-year - old female sustained multiple injuries in a major rta 6 months ago . she was travelling with family and friends in a four wheeler jeep when the driver of her vehicle tried to overtake a truck in high speed and had a head - on collision with the truck coming from opposite side . only 2 young ladies , sitting in the rear seat of the jeep , survived this fatal accident ( fig . 1 ) . they were admitted in a nearby hospital where they had primary resuscitative treatment and were then referred to our tertiary care center 5 days after the accident . on admission , this patient was in a state of hemorrhagic shock and was found to have multiple injuries , including multiple right rib fractures with haemothorax , bilateral segmental femur fractures ( fig . her medical condition was stabilized by multiple blood transfusions , intravenous broad - spectrum antibiotics , splinting of fractures by skeletal traction , right chest tube drainage and other supportive measures . she was then operated on in 2 sittings at the gap of 2 days to fix all the major fractures . firstly , the segmental fractures of both femora were fixed under general anaesthesia using intramedullary interlocking nails , taking the adequate precaution of padding the perineal and sacral areas . right side segmental femur fracture was fixed with an antegrade femoral nail ; whereas left comminuted segmental fracture was more proximal ( subtrochanteric ) therefore was fixed with synthes ' shaft fracture nailing system . she responded very well to the first surgery and hence after two days the sacral fractures were fixed using a sacral bar in a prone position . and then the patient was turned supine and anterior column fractures of both the acetabulum were fixed with pre - contoured reconstruction plates through the bilateral ilioinguinal approach . the postoperative courses after both surgeries were uneventful . she was allowed sitting in bed from the 2nd postoperative day and active and passive exercises were started . physiotherapy and wheelchair mobilization were advised for 6 weeks . at a follow - up of 3 months , she had shown neurological recovery and the ankle dorsiflexors were improved from the medical research council ( mrc ) grade 0 to grade 3 and at 6 months to grade 4 + . follow - up radiographs showed satisfactory healing of all the fractures in good alignment at 12 months ( fig . 4 , fig . 5 , fig . 6 ) she was allowed partial weight bearing mobilization with crutches after 2 months of the surgery . she not only survived this major accident but escaped from any major complication related to her fracture and treatment . there is paucity in the literature about the mechanism , priority and optimal treatment of the concomitant unstable pelvic and segmental femoral shaft fractures . due to non - availability of suitable guidelines to treat such complex injuries we consider that combined femoral shaft and unstable pelvic fractures are severe injuries and necessitate timely and aggressive management . the femoral fractures need precedence over pelvic fracture fixation . understanding the mechanism of such fracture pattern remains a challenge . malgaigne 's fracture is an unstable pelvic fracture through both pubic rami and the ilium or sacroiliac joint with vertical displacement . these fractures result from application of axial force through the femur , through extended knees when a motor vehicle occupant is bracing during frontal collision , or from dashboard injury to the knee , vertical shear forces are involved . it is an uncommon injury occurring from the axial force through the femur resulting in a posterior acetabular fracture and femoral shaft fracture . the mechanism of injury , in this case , could have been due to an axial force through the extended knee resulting in vertical shear force in the pelvis leading to bilateral acetabulum fracture and bilateral sacral fracture . the segmental comminuted fracture of bilateral shaft femur might have been due to crushing of both the bones between some heavy objects of the jeep body parts . it is , however , difficult to conceive and explain these injuries with any single mode of injury ; as the 4 wheeler had tumbled many times after the initial strike and , therefore , a multi - hit theory only can explain such an injury pattern . bilateral femoral fractures associated with unstable pelvic fractures and visceral damage have been reported with a very high mortality and morbidity rate . these patients should be initially managed with the advanced trauma life support ( atls ) protocol5 , 6 and once stable , surgical intervention should be considered . if the patient remains unstable the principles of damage control orthopaedics ( dco ) should be followed . this patient presented to us in a state of shock , thus priority for us was to stabilize the patient hemodynamically and once the patient was stabilized we proceeded for the definitive fixation of the fractures in staged manner , giving priority to femoral shaft fractures . in this case , we fixed both the femora in the first sitting with an interlocking nail , with minimal reaming . the patient was moved gently to the fracture table for the fixation of the femur and gentle traction was applied intraoperatively to prevent secondary injury to the pelvic fractures or to prevent re - bleeding from the pelvic cavity . subsequently , in the second sitting an open reduction and internal fixation ( orif ) of bilateral acetabulum fracture and bilateral sacral fractures was done . tscherne et al suggested that in patients with multiple closed fractures , femur fractures must be given priority over pelvis . an early and timely surgical intervention to fix all the major fractures helps the patient to overcome the medical complications and provide better rehabilitation . the data suggest that aggressive resuscitation for multiply - injured patients and early or delayed orif without application of external fixation will lead to overall low mortality rate .

the management of multiple complicated injured patients remains a great challenge despite advancements in modern medical care . we present a rare case of bilateral unstable pelvic fractures associated with bilateral segmental femoral shaft fractures . we have proposed a mechanism of such complex injury pattern and discussed the plan of management . we believe that a timely and aggressive surgical intervention to fix all the major fractures soon after medically stabilizing the patient helped our patient to overcome these serious and lethal injuries . it is necessary to establish an optimal protocol for management of such complex fractures by conducting prospective and multicentric studies in the future .

genital ulcerative disease can be defined as a condition in which there is a breach in the continuity of the epithelium of the genital skin and mucous membranes . the origin of sexually acquired genital ulcer diseases ( guds ) still appears deeply buried in antiquity . the advent of human immunodeficiency virus ( hiv)/aids over the past 25 years has further deepened the scope of morbidity , mortality , and various forms of clinical presentations guds . hiv / aids , which has no doubt created a fertile ground for sexually transmitted diseases ( stds ) to thrive , and vice versa , presently poses a serious health threat to at least a billion people of the global community . the ulcerative stds are major health problem in many developed and developing countries as a group of communicable disease , but prevalence rate is higher in developing countries . the importance of ulcerative std has increased considerably due to the fact that these lesions are a major cofactor in the transmission of the hiv , and hence it is necessary to provide prompt and effective treatment as early as possible . identification of the prevalent guds in hiv / aids patients in the locality would be an important guide toward choice of procurement and supply of relevant medications to the health centers in the region . a total of 50 cases were studied from the period extending from november , 2005 to december , 2006 . the history was taken in detail with general examination , local examination and systemic examination . laboratory investigations such as gram stain , tzanck smear , wet mount , 10% koh , giemsa stain , culture and sensitivity of discharge , biopsy were also done . serum venereal disease research laboratory ( vdrl ) and serum elisa for hiv were done in every case . specific diagnosis of genital ulcers was based on available medical history , clinical evaluation , and laboratory diagnosis . the study shows that the majority of patients i.e. , 29 ( 58% ) belonged to sexually active age group i.e. , 21 - 30 years [ table 1 ] . history of sexual exposure was positive in 68% of male and 4% of female patients . clinically maximum number of cases 19 ( 38% ) were of herpes genitalis followed by primary syphilis 16 ( 32% ) , chancroid 13 ( 26% ) , lymphogranuloma venereum 01 ( 02% ) and scabies 01 ( 02% ) [ table 3 ] . out of total studied patients five were of mixed stds and most common manifestation was the presence of multiple genital ulcers having different morphological appearance due to different causative organism . in clinically diagnosed cases of primary syphilis , the reactivity of serum vdrl [ table 4 ] was seen in 11 ( 84.61% ) out of 13 of cases . vdrl was also positive in 5 ( 39% ) out of 13 cases of chancroid , which suggest the presence of mixed infection . out of 16 cases of chancroid all the 16 were positive for pleomorphic gram - negative cocobacilli and 19 smears out of 19 cases of herpes genitals were confirmed by visualization of acantholytic cells and multinucleated giant cells . out of hiv sero - positivity was seen in 12% ( n = 6 ) cases of gud , with syphilis in 50.0% ( n = 3 ) , genital herpes in 33.33% ( n = 2 ) and chancroid in 16.67% ( n = 1 ) . vdrl reactivity and clinical diagnosis periheral smear examination among the hiv / aids attendees with guds the female gender constituted 18% of the 50 subjects . this finding appears different from the general pattern of presentations of stds with often higher frequency among females compared with males . the high incidence of guds among those aged 21 - 30 years is understandable as this corresponds to the most sexually active age group with the attendant risk for transmission of both hiv and other sexually transmitted infections . the pattern of genital ulcerative stds differs from country to country and from region - to - region , especially in large countries like india . frequency of clinical disease same in anand kumar , while nair in their study revealed that the maximum number of cases were of syphilis . hiv sero - positivity in the present study is comparable with the anand kumar study , but it was higher than aggarwal study and zamzachin study . the higher prevalence of herpes genitals in the present study reflect the changing trends in the pattern of the stds in our country . more males indulge in extramarital sexual relations which explain the higher prevalence in the male . gud increase the risk of transmission of hiv infection , among which chancroid has a higher risk for acquisition of hiv infection . studies have severally reported a high incidence of genital ulcers among hiv / aids patients when compared to the non aids group . findings from spain showed that herpes , syphilis and chancroid were the most common genital ulcers encountered among aids patients , and they in turn increase the risk of contracting hiv by several fold . similarly , in india , genital ulcers such as herpes , syphilis , lymphogranuloma venereum , granuloma inguinale , and chancroid were the most commonly encountered guds among hiv / aids patients . in sao paulo , brazil , herpetic and autoimmune ulcers were the most frequently encountered guds seen in 53 women presenting at a clinic without a definitive diagnosis . hiv was found to be generally more common among gud patients , especially syphilis and genital herpes .

introduction : genital ulcerative diseases are a major public health problem . the advert of human immunodeficiency virus ( hiv)/aids over the past 25 years has deepened the scope of morbidity , mortality , and various forms of clinical presentations of sexually transmitted diseases ( stds).materials and methods : a total of 50 cases having genital ulcerative diseases and std reporting to std clinic during the period of the year from november 2005 to december 2006 were included and detailed history and clinical examination were carried out and provisional diagnosis is made . laboratory confirmation of clinically diagnosed cases was done using laboratory tests such as s. hiv , venereal disease research laboratory , tzanck smear , gram stain , and giemsa stain.result:in the present study , the incidence of herpes progenitalis was ( 38% ) followed by primary syphilis ( 32% ) , chancroid ( 26% ) , lymphogranuloma venereum ( 02% ) , and genital scabies ( 02% ) . hiv sero - positivity was detected in 12% ( n = 6 ) cases.conclusion:hiv was found to be more common among genital ulcer disease patients , especially syphilis and genital herpes .

, the medical faculty and deans offices can not operate in isolation but must establish links with existing services run by the university , the city or the country , churches and so on . for example , kids ( children at university ) , an initiative by the university of heidelberg , the german national association for student affairs ( studentenwerk ) and the equality office collated all key institutions , advisory services , initiatives , childcare and financial support offers on the university s website in cooperation with local authorities and the state in a helpful and comprehensive way ( http://www.uni-heidelberg.de/studium/imstudium/kids/ ) . the deaneries are responsible for giving advice to students , their individual term plans and planning the academic progress of students . thus it gives food for thought if 56% of students state a need for advice regarding curriculum planning that 93% of respondents at the same time said that they are not in regular contact with their academic advisor about their study organisation , with 62% of respondents even claiming they do not know that the academic dean s office offers academic advisory services . everyday experience can not explain the survey results for the dean s office ; particularly in the light of conscious pregnancy planning and raising children while studying advice is vital , sometimes even before pregnancy . from the outset , the academic advisors present themselves as a first point of contact for study - related problems and pregnant students and students with children are always made to feel welcome when dropping in and sensitive advice is given when giving advice regarding the extra difficulties of their situation . perhaps the dean s office is seen by some students primarily as a body dealing with course regulations and examinations rather than as a neutral advisory office offering to take up problems without negative consequences for the students studies . the offers and advisory services the academic dean offers the dean s office will develop strategies for engaging the target groups more effectively and encouraging them to regularly visit the academic advisor in the dean s office . increasing the flexibility of degree courses is a legitimate request from student parents ; considering their group placement and exchange requests or the possibility of taking a break from the course and a flexible return to it should go without saying . similar requests have also been made by many other students who are in comparably difficult situations , for example , ill or disabled students , students caring for relatives , students who must self - finance their studies and foreign students , some of whom require support because of language problems , different learning cultures or problems with immigration issues . students who began their studies at a later stage of life , often following a first qualification , who resume studying after a break or as extreme long - time students who have exceeded the regular length of study require advice . many students approach the academic advisory services with special requirements regarding study planning that are not limitations through personal or social hardships but through their additional commitments or special engagements while studying . for example students who study two degrees in parallel , students on scholarships or students on other forms of sponsorship , students with unusual commitments in competitive sports , art , music , politics or social or scientific projects , as well as students who are active on the student council or hired as tutors by the faculty or aspiring to study abroad . from this angle , students with children are one of many student groups with legitimate needs and prioritisation of special groups is not possible . in addition , study regulations and principles of equal treatment and achievement of learning targets must apply to all students , even groups of students with special needs or problems . in general , timetables can not be adjusted according to the wishes and needs of students as many fixed aspects must be taken into account in the organisation of teaching . the number of teaching hours , examinations and group sizes are often specified by law , there are accommodation and staffing factors and , not least of all , didactic aspects of the curriculum . grouping together certain types of students into their own groups seems difficult due to the heterogeneity of needs and is also questionable from a didactic point of view . structured part - time medical studies are also not really an option as extending the period of study , which under normal circumstances is already six years and three months , could not be justified . on the other hand , an individual study extension for students can be easily arranged as the state examinations must not be taken at fixed dates and credits gained do not expire . individual solutions for part - time study in the practical year are available upon request for student parents . the feedback from the prenatal clinic that medical students are under extreme pressure to perform , discouraging pregnant students and sometimes leading to abortions is disconcerting . a survey carried out in heidelberg on motivation in medical studies ( heimi 2010 ) confirmed that performance pressure and fear of failure concerns many students : 11% of surveyed students are frequently or constantly afraid of not being able the meet the demands of the course , only 31% of students have never been worried about possibly having to quit the course . the idea of studying at an elite university can lead students to believe that only unburdened students who are able to fully perform permanently are welcome . not only is the quality of teaching important for the motivation of the students but also supportive environments and the certainty that students are not perceived as a nuisance . the university must recognise it as a special achievement when students manage to combine studying with raising children and that their studies are completed with and for the children . better advertising of the advisory services offered by dean s office , e.g. by promoting them on the homepage.improved information through networking the dean s office with the advisory services offered by the university for student parentsresponsiveness and flexibility in the organisation of studies for pregnant women and student parentsreducing presence requirements in some blocks and modules of some clinical courses or reducing attendance control . this is done in those teaching forms and course sections which permit independent study of the contents by the students at home , where possible supported by electronic media.forum on the learning platform for networking and exchange of experiences among the students with childrenensuring prenatal advisory centres inform students that they should also approach academic advisors at the dean s office in case of problems.requesting management to provide changing and nursing facilities in the dean s office better advertising of the advisory services offered by dean s office , e.g. by promoting them on the homepage . improved information through networking the dean s office with the advisory services offered by the university for student parents responsiveness and flexibility in the organisation of studies for pregnant women and student parents reducing presence requirements in some blocks and modules of some clinical courses or reducing attendance control . this is done in those teaching forms and course sections which permit independent study of the contents by the students at home , where possible supported by electronic media . forum on the learning platform for networking and exchange of experiences among the students with children ensuring prenatal advisory centres inform students that they should also approach academic advisors at the dean s office in case of problems . requesting management to provide changing and nursing facilities in the dean s office

increasing the flexibility of medical degree courses as well as individual advice and curriculum planning are essential needs of pregnant students and student parents . the results of the ulm study gave the academic advisers in the dean of studies office in heidelberg a large number of suggestions on how to offer sensitive , competent and needs - based advice to this target group . comprehensive reflection on many years of experience in giving advice and recent survey results leads to a series of concrete measures which will contribute to more family - friendliness in heidelberg s medical school .

defined as an abnormal development and growth of haemopoietic tissue outside the bone marrow(1 ) , extramedullary haemopoiesis(emh ) is usually a compensatory mechanism of myeloid and erythroid production outside the bone marrow and peripheral blood . this is usually due to increased breakdown or diminished production of erythrocytes , such as in myelofibrosis , thalassaemia and sickle cell anaemia ( 2,3 ) . post - traumatic emh is extremely rare and to our knowledge , there has only been one other reported case of post - traumatic emh ( 2 ) . we present a case of post - traumatic pelvic emh tissue causing lower urinary tract symptoms in a 52-year - old gentleman . he presented at the age of 19 to the emergency department after a motorcycle accident with a fractured pelvis , requiring fixation by wiring of the pubic symphysis and open reduction and internal fixation of the left acetabulum via a trochanteric osteotomy side approach(fig . he had previously experienced similar trauma , where he suffered a right hip fracture and trauma to the bowel , requiring a right total hip replacement and reparative bowel surgery , respectively . x - ray of the pelvis showing the wiring of the pubic symphysis , internal fixation of the left acetabulum and right total hip replacement 33 years later , he presented to a urologist with 12-month history of lower urinary tract symptoms of nocturnal enuresis , urinary frequency , weak urinary stream and incomplete emptying . he had no history of urinary tract infections , but had experienced some recent weight loss . other significant medical history included obesity , excessive alcohol consumption , paroxysmal atrial fibrillation , chronic tophaceous gout , rheumatoid arthritis , and vascular disease . his prostate was smooth on palpation , but the size was thought to be difficult to determine . this initiated a psa test ( 0.29ug / l ) and a subsequent ultrasound scan of the renal tract failed to demonstrate any abnormalities of the bladder or a significant post - voidal residual . a flexible cystoscopy was then undertaken , revealing a normal sized prostate and urethra , but noted some extrinsic compression of the bladder . an axial section of the ct demonstrating a 6.7x6cm.3x7.3 cm left pelvic lesion adjacent to the trauma site . arrow denotes the emh lesion a ct scan demonstrated a 6.7x6.3cmx7.3 cm well - defined left pelvic mass immediately medial and adjacent to the left acetabulum compressing the bladder and the iliac vessels . the mass was heterogeneous in density comprising of both muscle and fat with no calcifications . he underwent a repeat staging - ct , mri , whole body thallium scan , and a ct - guided biopsy . the mri scan confirmed a lobulated well - circumscribed mass with a heterogeneous t1 and t2 appearance . areas of hyperintensity reported on ct corresponded to fatty components within the mass , while the rest of the mass appeared relatively hypointense to skeletal muscle , and was thought to be consistent with a liposarcoma . the single photon emission computed tomography ( spect ) scan demonstrated low - grade activity in the mass and the staging - ct did not reveal any signs of malignancy . a confirmatory ct - guided biopsy however diagnosed the mass as emh tissue , while a ct angiogram demonstrated no external compression of the iliac vessels . arrow denotes the emh lesion this patient was subsequently discussed at a multidisciplinary meeting , where it was decided that in view of the urinary symptoms and his high operative risk , the mass should be treated with ct - guided radiofrequency ablation using a multi - lined electrode . however , the patient declined treatment and was temporarily lost to follow up after moving interstate . two years later , he presented to the hospital with bowel obstruction secondary to an incisional lumbar hernia , and the follow up ct scan ( figures 2 and 3 ) revealed no increase in the size of the mass , and repeat biopsy re - confirmed the presence of emh . emh is most commonly found in the spleen , liver and sometimes in the lymph nodes . emh is usually asymptomatic(4 ) and any symptoms are related to the location of the lesion(1 ) . where emh occurs in the pelvis , patients may present with abdominal or pelvic discomfort , ascites , renal insufficiency , bladder involvement , and systemic symptoms such as fever or chills(1,4 ) . in this patient , emh was diagnosed by ct , mri , spect - ct scan and ct - guided biopsy . cts commonly aid the diagnosis of emh(3,5 ) , and usually appears as a lobulated heterogeneous solid mass with smooth margins and similar density to that of soft tissue but slightly higher than that of fluid(3,6,7 ) . the characteristic finding on mri is a well - encapsulated lesion of slightly higher intensity than muscle and bone marrow on t1 and t2-weighted images , consistent with fatty tissue(3,5,8 ) , and uniformly enhanced with gadolinium injection(3,7 ) . nuclear imaging using technetium-99 m ( tc ) ( 4 ) and angiography ( demonstrating the hypervascularity ) can also be used in diagnosis of an emh lesion(8 ) . however , histopathological examination of tissue by ct - guided biopsy(6 ) , ultrasound - guided biopsy(9 ) , or diagnostic excision of the suspected mass is often essential to exclude malignancy and confirm the diagnosis(2,5,7,8 ) . the microscopic features of emh often reveal haemopoietic cells with polymorphous infiltrates(2,5,6 ) , while macroscopically a soft , elastic , lobulated fatty mass is seen , usually adherent to adjacent structures , with a homogeneous erythematous cut surface(2,5,6,7 ) . there is limited evidence on management of this rare condition . in studies where a conservative approach was adopted , however , in events of increasing pressure symptoms from the mass(3 ) , neurological deficits(1 ) , and anaemia due to thalassemia(10 ) , treatment maybe necessary . surgical resection is often reserved for symptomatic cases or when the diagnosis is uncertain(2,5,7 ) . due to the high efficacy and non - invasive nature , low - dose radiotherapy is also occasionally used for symptom control in emh , as primary or adjuvant therapy to surgery(1,6 ) . non - surgical approaches such as hypertransfusion and iron chelation with desferrioxamine to relieve anaemia and suppress emh , or utilisation of hydroxyurea to stimulate fetal haemoglobin synthesis have also been described in management of emh(10 ) . however , a conservative approach maybe used in asymptomatic patients , while symptomatic cases often requires surgical excision or radiotherapy .

extramedullary haemopoiesis ( emh ) is the abnormal development and growth of haemopoietic tissue outside the bone marrow . it is usually asymptomatic and occurs in the presence of myelodysplastic syndromes . in this report , we describe the first post - traumatic emh presenting with lower urinary tract symptoms .

encephalotrigeminal angiomatosis , or sturge - weber syndrome ( sws ) , is an uncommon nonhereditary developmental condition with hemangioma as a disturbing feature . the pathognomonic features of this syndrome are venus angiomas of the leptomeninges extending over the cerebral cortex with ipsilateral angiomatous lesions , unilateral facial nevus along the distribution of one or more divisions of the trigeminal nerve extending up to the midline and epileptic convulsions . commonly the clinical features are convulsions , hemangiomas , abnormal radiographic findings , ocular involvement , and hemiplegia . on the basis of systems involved sws is classified as complete trisymptomatic when all three organ systems ( eye , skin , and cns ) are involved , incomplete bisymptomatic when the involvement is either oculo - cutaneous or neuro - cutaneous and incomplete monosymptomatic when there is only neural or cutaneous involvement . presenting themselves as one of the benign conditions their entire course runs from 1 month to 10 years after which they usually regress . hemangiomas appear during first 2 - 3 weeks of infancy and are most commonly seen in females than males ( 3:1 to 5:1 ) . the incidence in caucasian infants ranges from 10 to 12% and lower in dark skinned infants . they may be solitary or present in many locations measuring 0.5 cm to an extensive area . the life cycle of majority of hemangiomas is characterized by rapid proliferative phase seen during first 2 years followed by a ceased growth lasting for 7 - 8 years followed by the phase of involution over next few years . in the present case hemangiomatous lesion divided the face in the two halves from midline with prominent portwine stains and was associated with pyogenic granulomatous lesions . a 12-year - old girl reported to the department of pedodontics rdc loni with a complaint of swelling in the lower front gum region since 3 months . clinically there was an isolated gingival swelling in the lower left anterior region between central and lateral incisors ( 31 and 32 ) . the swelling was red and shiny in appearance measuring about 2 1 cm in size extending from mesial surface of central incisor to the mesial half of canine on the labial side and was extending on the lingual side of incisors measuring 0.8 0.5 cm in size . both the swellings were connected at the interdental area of central and lateral incisors [ figures 1a and b ] . on palpation the swelling was a pedunculated mass , soft and easily movable from the base . extraorally the face was asymmetrical with slight enlargement on the right side of the face . there was a prominent scar on the right side of the face in upper buccal region [ figure 1c ] . parents revealed a history of surgery 7 years ago for a red swelling in the scarred area . localized gingival enlargement between 31 and 32 labial and lingual swelling connected at the interdental area of 31 and 32 enlarged right half of the face reddish in color with arrow showing scarred area intraorally right half of the mouth was markedly red affecting labial and buccal mucosa , buccal vestibule , floor of mouth , tongue and palate while left side did not show any abnormalities . intraoral periapical radiographs of the 31 , 32 , and 33 region and opg were advised to rule out any bony involvement . the radiographs did not reveal any significant problems except presence of initial bone loss from the interdental area of 31 and 32 . since the lesion had a pedunculated base with little bony involvement excisional biopsy was carried out carefully followed by bony curettage . histopathological examination of the excised mass showed numerous endothelium lined spaces , abundant fibroblasts , collagen fibers , and polymorphonuclear leucocytes revealing features of pyogenic granuloma [ figure 2 ] . at the end of 1 month , the lesion had uneventful healing [ figure 3 ] . six - month follow - up was quite satisfactory and there was no evidence of any recurrence . during surgery and curettage the amount of bleeding was controllable and no additional steps were required to stop the bleeding . this could have been due to the presence of granuloma on the left side which was not affected by the vascular lesion . histopathology showing multiple endothelium lined spaces and connective tissue fibers suggestive of pyogenic granuloma six months follow up showing satisfactory healing in the present era of science , anomalies are toward fading side but some anomalies are really disturbing . although majority of hemangiomas recede over a period of 10 - 15 years , in few cases they may continue to exist and disturb the esthetics and function . since sws is a disease with hemangiomatosis , such growths on gingival can be expected . this complication of gingival enlargement could be due to increased vascular component and precipitated by local irritation by plaque and calculus . a significant increase in the numbers of mast cells in pyogenic granuloma with similar vascular lesions has been reported . the average density of mast cells ( mcs ) per mm square appearing in the central region of the pyogenic granuloma is shown to be higher compared to adjacent nevus and normal skin indicating that mcs are closely associated with angiogenesis in pyogenic granuloma . the diagnostic tools for such cases include ultrasound a relatively economic non - invasive technique , ct scanning , and mri . multidisciplinary treatment approach including plastic surgeons , pediatric surgeons , anesthetists , hematologists , etc . oral prednisone 1 - 2 mg per kg for 6 months and triamcinolone given intralesionally 1 to 2 mg per kg per month for 6 months has documented good relief from the condition . interferon - alfa 2a , bleomycin , and cyclophosphatamine are also used . use of nd : yag laser is commonly followed surgical procedure by many plastic and reconstructive surgeons . the lesions which are superficially situated and smaller in size but the effectiveness of lasers in deeply situated skeletally involving hemangiomas still requires extensive study . in the present case , hemangioma with portwine stains present on the right half of the face was an unusual finding . the patient had undergone cosmetic surgery for the same ; however , the buccal aspect still showed signs of scarring . surprisingly the mass representing pyogenic granuloma was seen on left unaffected area of lower jaw making it difficult to limit the diagnosis of hemangioma on other side . keeping in mind the potential complication in the form of hemorrhage all precautions were taken and emergency team was ready if difficult situation would exist .

vascular lesions represent one of the rare disorders affecting overall quality of life of a child . a wide variety of these conditions are known , ranging from a simple nevus to life - threatening hemangiomas . these conditions make the treatment options more complex due to the fear of uncontrollable bleeding . the present case is one of the rare combinations of sturge - weber syndrome and pyogenic granuloma . conditions of importance and treatment options keeping hemangioma in mind are discussed .

it is known that core stability can enhance the muscles located nearby abdomen , lumbar spine and pelvis1 and play important role to improve balance ability and trunk stabilization2 . core muscles are composed of the muscles of nearby abdomen and pelvis , such as rectus abdominis , external / internal oblique abdominis , transverse abdominis , erector spinae , quadratus lumborum , multifidus , gluteus medius3 . those muscles are playing an important role providing stabilization during moving legs and arms . among them , it is known that transverse abdominalis and multifidus provide spinal stabilization to deep muscles4 . in order to strengthen core muscles , various methods of exercises such as swiss ball1 and bridge exercise5 are used . but the lack of studies and definite evidences are founded whether those methods are effective to deep muscles such as transverse abdominalis and multifidus . adim is a kind of exercise technique to increase intra - abdominal pressure by pulling lower abdomen without moving spine and pelvis6 , and possible to contract transverse abdominalis and multifidus selectively , which is utilized for spinal stabilization exercise7 . lee et al.6 reported the muscle activation of trunk muscles is increased when back pain patients who are instable on lumbar spine exercise adim , and chon et al.8 reported the muscle activation of deep core muscles is increased when the patients perform adim including dorsiflexion . but in the review of preceding research , most studies are executed on muscle activation of deep muscle by simply applying adim . therefore , the purpose of this study was to investigate the effects of visual biofeedback using ultrasonography on muscle activity of the deep trunk muscle in healthy adults . information on the study and written informed consent according to the ethical standards of the declaration of helsinki were provided to all subjects prior to their participation , and all agreed to participate in the project . the average ages , heights , and weights were 22.70 2.06 years old , 171.15 9.18 cm , and 66.86 8.88 kg in the experimental group , respectively . the adim ( abdominal drawing - in maneuver ) are executed for subjects through monitoring the status of muscle contraction using ultrasonic waves . and motor control exercises are performed during 6 weeks , 20 minutes / a day and three times / a week . ultrasonic measurement for the thick of transverse abdominal muscle is executed by positioning the probe to the center of upper parts on iliac crest at central midaxillary line in the right . and in order to reduce measurement error , we selected an expert who is 5 years more experienced in ultrasonic measurement field . we firstly asked the subject to pose putting a pillow under the head , bending hip and knee joint to 60 degrees , and taking crook - lying position , and adjust monitor position for them to watch the ultrasonic image ( achieve cst , v2u healthcare , pte , ltd . , therapist gives instructions orally to the subject please make your abdomen constriction like drawing your belly with the utmost effort while breathing as usual9 , and subject execute the exercise by checking on his transverse abdominal muscle contraction via the monitor . total time of exercise are 20 minutes ; allowing the subject to rest for 10 minutes after contraction of transverse abdominal muscle for 10 minutes . we measured electrical activities by using electromyogram electrode attached to the area of muscular fiber and pressing muscle parts following the direction of muscle texture in order to find the positions10 . the attached locations of surface electrodes were as follows11 ) : ( 1 ) for rectus abdominis : 5 cm from top of belly , ( 2 ) for internal oblique abdominis : the middle point between belly line and asis , ( 3 ) for internal oblique abdominis : in the center of the triangle formed by a horizontal line between the anterior superior iliac spine of the innominate and the umbilicus , midline , and the inguinal ligament , ( 4 ) for lumbar multifidus : 2 cm lateral to the spinous process at the l4l5 interspace . we executed bridge exercise to measure muscle activity at reference voluntary contraction of each muscle12 . after we collected the data value for 5 seconds at maximal voluntary isometric contraction of each muscle , and used the amount of average electromyographic signals reference voluntary contraction ( % rvc ) during only 3 seconds excluding 2 of beginning and 1 of latter part from total 5 . the subjects showed significant improvements in internal oblique abdominis and lumbar multifidus muscle after intervention ( p<0.05 ) ( table 1table 1.the within - group and between - group comparisons for the outcome measures ( unit : % rvc)eg ( n=10)rectus abdominispre - test10.6 4.0post test12.2 3.7change value1.6 6.4external oblique abdominispre - test12.6 2.8post test13.8 3.9change value1.2 3.6internal oblique abdominispre - test16.8 4.9post test 22.0 4.3**change value 5.2 4.5lumbar multifiduspre - test17.0 7.4post test 23.9 2.9**change value6.9 in this study , we compared and analyzed the muscle activation for trunk muscle activation , especially surface muscle of rectus abdominis , external oblique abdominis , and deep muscles of internal oblique abdominis , lumbar multifidus using visual feedback of adim which conduct targeting health adults . as like the above , in the preceding research by using visual feedback , kim et al.13 showed the subject s contraction exercise of pelvic floor muscle through visual feedback can increase muscular activation in transverse abdominis and its thickness is thicker . also , park et al.14 report breathing exercise using visual feedback can increase pulmonary function and respiration muscle activation significantly . lee et al.15 report that visual perception and sitting balance are improved when visual biofeedback training is conducted for stroke patients . second , the absence of follow - up after the end of the intervention does not allow for determination of the durability of the effect of this therapy . further studies , including a long - term follow - up assessment , are needed to evaluate the long term benefits of visual biofeedback therapy .

[ purpose ] the objective of this study is to investigate the effect of visual biofeedback using ulatrasonography on the functional improvement of deep trunk muscle . [ subjects and methods ] this study selected ten healthy people without orthopedic history and information on the study . the average ages , heights , and weights were 22.70 2.06 years old , 171.15 9.18 cm , and 66.86 8.88 kg in the experimental group , respectively . the abdominal drawing - in maneuver were executed for subjects through monitoring the status of muscle contraction using ultrasonic waves . and motor control exercises were performed during 6 weeks , 20 minutes / day and three times / week . we collected the data using electromyography mp150 system ( biopac system inc . , ca , usa ) in order to measure trunk muscle activation . [ results ] the subjects showed significant improvements in internal oblique abdominis and lumbar multifidus muscle after intervention . [ conclusion ] visual biofeedback training using ultrasonography might be effective in improving function of the deep trunk muscle .

a 33-year - old south indian male presented with complaints of pain in the left eye ( le ) with painful eye movements since 25 days and gradual progressive worsening of vision in his le since 20 days . there was no history of fever , chronic cough , evening rise of temperature , lymphadenopathy , contact with tb , trauma , headache , vomiting , tinnitus , vitiligo or joint pains . he had no history of hypertension , diabetes , tb and no other significant medical history . on examination , his best corrected visual acuity ( bcva ) of right eye ( re ) was 20/15 , n6 and le was 20/30 , n6 . le showed grade ii relative afferent pupillary defect ( rapd ) with disc edema [ figs . 1 and 2 ] . routine baseline investigations including erythrocyte sedimentation rate ( esr ) and peripheral smear were normal . special investigations like anti - nuclear cytoplasmic antibodies ( p - anca , c - anca ) , homocysteine , angiotensin converting enzyme levels were all normal . b scan of le showed disc elevation with normal choroidal thickness . no subtenon fluid or any mass lesion automated perimetry with humphrey field analyzer ii 302 test showed enlarged blind spot in le . after physician 's clearance , iv methyl prednisolone ( ivmp ) 1 g / day was given for 3 days and then substituted with oral prednisolone 1 mg / kg body weight with weekly 10 mg tapering dosage . colour photo of the patient at first presentation showing disc edema autofluorescence picture of the patient at first presentation showing disc edema at 1-month follow - up , patient was symptomatically better with bcva 20/16 be . patient was advised to continue oral prednisolone 10 mg for 4 weeks and then stop medication and review . there was no history of pain , fever , headache or any other complaints locally or systemically . le showed rapd with disc edema and a subretinal mass [ figs . 3 and 4 ] . laboratory investigations showed normal blood counts with normal esr ( 13 mm / h ) . hiv was negative while quantiferon ( cellestis limited , carnegie , victoria , australia ) tb gold test was positive . high resolution computed tomography ( hrct ) chest showed multiple discrete sub - centimeter , noncalcified , pretracheal and circumaortic lymph nodes suggestive of old healed tb . b scan le showed exudative retinal detachment with subretinal fluid in the peripapillary area and posterior pole . peripapillary choroidal thickness was 2 mm and an elevated lesion was noted over the optic nerve head with moderate to high surface reflectivity and moderate internal reflectivity . based on hrct report suggestive of healed tb , a positive quantiferon tb and mantoux test , patient was diagnosed to have subretinal abscess with exudative retinal detachment of presumed tubercular etiology . patient was started on a 9 months course of anti - tubercular therapy ( att ) with tapering course of oral steroids over 6 weeks under the care of a physician . he was advised to review in 1-week but the patient reviewed after 1-month ( his last follow - up ) . he was symptomatically better with his bcva improving to 20/160 in le with a healed tubercular granuloma and subretinal fibrosis [ figs . 5 and 6 ] . as the patient had shown good response to att , our diagnosis was confirmed and hence ocular fluid tap for polymerase chain reaction ( pcr ) test was avoided . colour photo of the patient at 7 month showing subretinal abscess and disc edema autofluorescence picture of the patient at 7 month showing subretinal abscess and disc edema colour photo at 8 month showing resolution of inflammation with subretinal fibrosis , one month after starting anti - tuberculosis therapy autofluorescence picture at 8 month showing resolution of inflammation with subretinal fibrosis , 1-month after starting anti - tuberculosis therapy ocular tb can result from hematogenous spread , direct local extension from respiratory tract , or it can be delayed hypersensitivity reaction . choroid is the most commonly involved site with posterior uveitis being the most common presentation . the main types of choroidal involvement include choroiditis , tubercles , tuberculomas and subretinal abscess . large tuberculomas may undergo liquefactive necrosis and form yellowish subretinal abscess with little vitreous inflammation . rarely , subretinal abscess can rupture into vitreous cavity leading to endophthalmitis or panophthalmitis . with timely att microbiological ( culture / acid - fast bacilli staining / pcr ) evidence of mycobacterium tb from intraocular fluid or tissue constitutes the gold standard for diagnosing intraocular tb . usually the diagnosis is presumptive as ocular specimens can rarely be obtained easily . the current criteria of making a presumptive diagnosis of intraocular tb is based on a combination of clinical features suggestive of ocular tb with corroborative evidences such as a positive mantoux test , positive interferon - gamma release assay , radiographic findings , exclusion of known nontubercular uveitic entities , and a positive response to att . subretinal tuberculomas and abscesses have been successfully managed surgically . if diagnosed early , they are amenable to medical treatment . the regimen consists of isoniazid , rifampicin , ethambutol , and pyrazinamide for 2 months and then isoniazid and rifampicin for 912 months . early treatment with att not only takes care of the active infection but also decreases the risk of developing recurrences of uveitis . a favourable response to att was evident within 4 weeks in our case . low dose steroids are given concomitantly with att for 46 weeks since they have a protective effect against jarisch ocular tb , presenting as disc edema and followed by subretinal abscess has not been reported in literature to the best of our knowledge . it is possible that iv steroids could have caused a flare up of latent tb which manifested later . it is also possible that that initial disc edema and the later subretinal tubercular abscess were two separate disease processes . we can never reach a conclusion on this as mantoux and quantiferon tb gold tests were not done initially . this case report shows that before starting ivmp , tb has to be ruled out at least by a mantoux and/or quantiferon tb gold test . in cases where ivmp has to be administered and since the disease is treatable , a timely diagnosis and treatment is of paramount importance to salvage the eye for a good outcome .

we report a case of ocular tuberculosis ( tb ) which initially presented with disc edema and was mistaken for optic neuritis . with no definite pathology being identified , the patient was treated on the lines of optic neuritis with intravenous ( iv ) steroid with beneficial effect . ocular tb was suspected when he presented later with a subretinal abscess . based on positive mantoux , quantiferon tb gold results and radiographic findings , a diagnosis of subretinal abscess of presumed tubercular etiology was made . the patient was successfully treated with anti - tubercular therapy . to the best of our knowledge , this is the first case report of ocular tb presenting as disc edema followed by subretinal abscess .

in a study in the previous issue of critical care , thooft and colleagues investigated the impact of increasing mean arterial pressure ( map ) by norepinephrine ( ne ) on systemic hemodynamics and organ perfusion in a series of patients with septic shock . the increase in map from 65 to 85 mm hg was associated with increased cardiac output and mixed venous blood oxygen saturation ( svo2 ) and a decreased blood lactate level . the increase in map was also associated with improvement of the microcirculation state as assessed by near - infrared spectroscopy ( nirs ) at the thenar eminence level in 13 patients and by sidestream dark field ( sdf ) imaging at the sublingual level in 6 of them . nirs technology allows investigators to evaluate the functionality of the thenar eminence microcirculation through the measurement of the muscle tissue oxygen saturation ( sto2 ) and its changes in response to a vascular occlusion test ( vot ) . sdf videomicroscopy allows investigators to assess the sublingual microvascular blood flow and capillary density by using several indices . the presence of marked microvascular abnormalities detected by each of these techniques has been associated with increased mortality in septic shock . before being enrolled , the patients of thooft and colleagues had already been stabilized at an map of 65 mm hg with fluid therapy and ne administration and their svo2 was above 65% , in accordance with surviving sepsis campaign guidelines . although these goals appeared to have been achieved , severe derangements of organ perfusion were detected by both the nirs and sdf techniques . this agrees with the concept that , in septic shock , microcirculatory abnormalities can persist despite apparent correction of macrocirculatory abnormalities . however , it is still unclear whether the persistence of microcirculatory abnormalities at the early phase is related only to intrinsic septic organ / tissue injury or is a consequence of insufficient macro - hemodynamic resuscitation and , in particular , achievement of a still suboptimal organ perfusion pressure . current recommendations suggest an map of at least 65 mm hg given that , in patients with a history of hypertension or other vascular comorbidities or in those with increased abdominal pressure , a higher level of map may be required . however , increasing the doses of ne carries the theoretical double risk of ( a ) decreasing cardiac output and oxygen delivery through an increased afterload effect and ( b ) worsening tissue perfusion through excessive peripheral vasoconstriction . recent studies have evaluated the effects on cardiac output and organ perfusion markers of using ne to increase map from 60 ( or 65 ) mm hg to 85 ( or 90 ) mm hg in patients with septic shock [ 8 - 10 ] . all of the studies supported the idea that , in spite of the increase in cardiac output , achieving the upper map target is not always associated with a remarkable improvement in organ perfusion . in contrast to previous studies , the study by thooft and colleagues demonstrated that an map target of 85 mm hg might be more appropriate than 65 mm hg for the microcirculation . one of the strengths of the study is that these results were found by using two different techniques : nirs and sdf imaging . the higher sto2 reperfusion slope ( during a vot ) at the highest level of map suggests that some degree of microvascular recruitment occurred at this level , confirming results found in patients with severely hypotensive sepsis . in addition , increasing map from 65 to 85 mm hg significantly improved two of the sdf - derived indices : the perfused vessel density and the microvascular flow index . this suggests that both microvessel recruitment and microcirculatory blood flow increased at the map of 85 mm hg . these findings can be the result either of a proper perfusion pressure effect in some pressure - dependent areas or of the increase in systemic blood flow observed at the highest level of map . the association of increases in cardiac output with ne - induced increases in map is a common finding that has been reported previously [ 8 - 13 ] . clearly , the results of thooft and colleagues argue against the idea that , owing to excessive vasoconstriction , ne could exert deleterious effects on the microcirculation when an map of 85 mm hg is targeted . it is important to note that 85 mm hg is still low compared with map values of the healthy population , especially in the age group of the study by thooft and colleagues . because the sdf analysis was conducted on only 6 of the 13 patients in the study by thooft and colleagues , the interpretation of their data must be cautious . it must be underlined that , using study designs similar to that of thooft and colleagues in the early phase of septic shock , jhanji and colleagues and dubin and colleagues reported no overall change in sublingual sdf - derived variables with ne - induced increases in map ( above 60 mm hg in 16 patients and 65 mm hg in 20 patients , respectively ) . nevertheless , dubin and colleagues reported an inverse correlation between the baseline level of the sublingual microcirculation state and the microcirculatory response to the ne - induced increase in map from 65 to 85 mm hg . thus , septic patients with normalized microcirculation ( after initial hemodynamic resuscitation ) might not benefit from any additional increase in map above 65 mm hg . in contrast , septic patients with persistent altered microcirculation , though surviving sepsis campaign recommended endpoints are achieved , might benefit from a further increase in map beyond the ' magic ' value of 65 mm hg . the results of thooft and colleagues are in agreement with this sensible concept , which clearly needs to be implemented in clinical practice . this paper , like other recent ones , has the merit of bringing to light the idea that , at least during the early phase of sepsis , the microcirculation is not dissociated from the macrocirculation , despite what is claimed by pioneers of the microcirculation evaluation . more importantly , the paper suggests that bedside assessment of microcirculation might help clinicians to define the optimal level of macrocirculatory resuscitation targets ( for example , map and svo2 ) in each patient . map : mean arterial pressure ; ne : norepinephrine ; nirs : near - infrared spectroscopy ; sdf : sidestream dark field ; sto2 : muscle tissue oxygen saturation ; svo2 : mixed venous blood oxygen saturation ; vot : vascular occlusion test .

the surviving sepsis campaign guidelines suggest targeting a mean arterial pressure of at least 65 mm hg to maintain organ perfusion pressure during septic shock . however , the optimal mean arterial pressure can be higher in patients with a history of hypertension or other vascular comorbidities or in those with increased abdominal pressure . in a given individual , the adequate mean arterial pressure target can be difficult to define with the routine hemodynamic parameters ( for example , cardiac output , central or mixed venous blood oxygen saturation , and urine output ) . near - infrared spectroscopy and sidestream dark field imaging have emerged as promising technologies for monitoring the microcirculation at the bedside . these new methods could provide additional clues to help define the adequate blood pressure to target during the resuscitation phase of septic shock .

in the almost 13 years since the first whole human genome was sequenced and published , tremendous advances in technology have enabled the sequencing of human genomes for a fraction of the cost and time . however , although the cost of sequencing has dropped considerably , large - scale whole - genome sequencing remains challenging , particularly in the clinical arena . this is due to the still significant cost of sequencing an entire human genome , and the challenges of analyzing enormous amounts of data with tools that are not standardized to a level acceptable for routine diagnostic use . cheap and high - quality targeted sequencing is key for a number of clinical research applications , including large - scale variant screening in disease genes or as follow - up for genetic markers identified as significant in genome - wide association studies . various methods have been developed to enable whole - exome sequencing and targeted - region sequencing . early on , solid - state capture arrays were used , but these were expensive and had relatively complex protocols . in - solution capture and pcr - based enrichment methods have reduced the cost and complexity of protocols considerably . these improvements led to a wider adoption of next - generation sequencing and , in the past 12 months particularly , an increase in the use of targeted resequencing as a diagnostic tool . for example , pcr - based methods require highly multiplexed oligonucleotide pairs targeted to heterogeneous sequences with a range of melting temperatures and cg content to generate hundreds or thousands of amplicons in a single tube . hybridization - based methods exhibit significantly more off - target capture than other enrichment methods , do not capture repetitive sequences , and poorly cover gc- and at - rich regions . methods employing ' capture by circularization ' ( figure 1 ) , such as connector inversion probes ( cips ) , also have problems . these methods use single - stranded dna molecules with gene - specific targeting regions at the 5 ' and 3 ' ends that are complementary to the targeted genomic dna . after hybridization of the targeting ends of the cip to the genomic dna , a single - stranded dna circle is formed and closed by gap filling and ligation . the single - stranded dna circle is then linearized by restriction digest , and the target region is enriched by pcr and finally sequenced . cips require a large backbone for the probes to capture targets efficiently , which makes them expensive and difficult to manufacture . clpp captures both strands of the targeted genomic dna , generating two complementary single - stranded dna circles . each of the strands is then sequenced in the forward and reverse direction to yield four unique reads . cip captures only one strand of the target genomic dna region and generates a single - stranded dna circle . the size of a target region is limited to a few megabases , which restricts the number of genes / exons that can be included in a clinical sequencing panel . in addition , all current capture methods use only one strand of genomic dna , missing out on an additional level of possible accuracy . by contrast with standard capture methods , the complementary long padlock probe ( clpp ) approach , as presented by shen et al . in a recent article , captures both strands of the target region , effectively doubling the target sequence information compared with other capture methods . this is achieved by generating double - stranded cips that are incubated at high temperatures to create single dna strands , and then hybridized to the sense and antisense strands of genomic dna , effectively forming two complementary single - stranded dna circles . in addition , clpp enables the sequencing of both strands in both the forward and reverse direction ( shen et al . call this reciprocal paired - end sequencing ) , resulting in a total of four unique sequence reads per template . this redundancy reduces uneven coverage due to differences in the amplification efficiencies of the target regions , and increases coverage and accuracy . this should lead to increased confidence in variant calls in the downstream bioinformatics analysis , and might allow for a reduced average depth of sequence coverage resulting in less sequencing per sample - thus lowering cost . also demonstrate that copy number variation ( cnv ) detection can be improved with this enrichment method owing to its significantly better discrimination of high- and low - covered targets . an additional interesting potential application for clpp is the targeted resequencing of problematic dna samples derived from formalin - fixed paraffin - embedded ( ffpe ) tissues . dna extracted from ffpe samples frequently contains lesions such as abasic sites that lead to a significant increase in sequencing errors when using traditional single - strand sequence capture methods . owing to the ability of clpp to capture both strands although clpp appears to be better suited than traditional cips for clinical use , both methods require a large sample size to be economical because of the initial cost of assay development . furthermore , to our knowledge , reagents based on clpp are not yet commercially available , which poses a challenge to its widespread adoption . clpp is an innovative new approach for high - throughput target enrichment for next - generation sequencing . it improves on a number of shortcomings of current targeted sequencing methods such as accuracy , cnv detection and cost . most compelling is its ability to preserve strand information and separately sequence sense and antisense strands . beyond the resulting improvement of variant detection fidelity , other applications that rely on double - strand targeting could benefit . such applications include problematic dna samples , where redundancy is important to retrieve as much information as possible because of damage to a single dna strand . cips : connector inversion probes ; clpp : complementary long padlock probes ; cnv : copy number variation : ffpe : formalin - fixed paraffin - embedded .

targeted next - generation sequencing is becoming a common tool in the molecular diagnostic laboratory . however , currently available methods to enrich for regions of interest in the dna sequence suffer from drawbacks such as high cost , complex protocols , lack of clinical - level accuracy and uneven target coverage . a target - enrichment approach using complementary long padlock probes described in a recent article significantly improves on previous methods in most of these areas.see related research : http://genomemedicine.com/content/5/5/50

the international classification of headache disorders recognizes three subsets of low volume headache , one of them being spontaneous intracranial hypotension ( sih ) . sih has been attributed to a breach of dural diverticulae or tearing of nerve root sheaths . there may be a clear trigger or at times it may occur without a precipitant . sih is not a common syndrome and clinical manifestations at times may make the diagnosis difficult . we present a case where rnc was helpful in confirming the diagnosis of a suspected sih . a 31-year - old male presented to us with the chief complaints of headache and diplopia . the symptoms presented 15 days back when he suddenly developed occipital headache with neck stiffness followed by multiple episodes of vomiting occurring in the next 24 h. the pain was relieved within 15 min of lying down and recurred after 15 min of upright posture . there was no history of fever , limb weakness , associated ear or nasal discharge , any trauma or prior lumbar puncture . a lumbar puncture revealed low csf opening pressure and on analysis , normal sugar , high protein content of 200 mg / dl with 10 cells ( all lymphocytes ) was seen . no organisms were seen on microscopy and culture was negative . a magnetic resonance imaging ( mri ) brain with gadolinium contrast was performed , which showed diffuse pachymeningeal enhancement [ figure 1 ] . sih was suspected and the patient was referred to the department of nuclear medicine for radionuclide cisternography ( rnc ) . gadolinium enhanced t1 weighted ( 1a ) sagittal ( 1b ) axial and ( 1c ) coronal magnetic resonance imaging ( mri ) images showed diffuse and linear enhancement of the meninges along the entire cerebral convexities ( thick arrow ) and the inter hemispheric fissure ( thin arrow ) after explaining the procedure , a written consent was obtained from the patient and 10 mci of 99 m technetium diethylenetriaminepenta acetic acid was injected via a lumbar puncture into the sub - arachnoid space . serial images were obtained ( philips precedence 16 single - photon computed emission tomography computed tomography [ spect - ct ] ) in anterior , posterior , and lateral views with the patient in supine position at 1 h , 2 h , 4 h and 24 h. gradual ascent of tracer was seen along the spinal axis . there was early visualization of the kidneys and bladder on the 1 h delayed image [ figure 2 ] . subtle extra - dural tracer accumulation of radiotracer was noted in the region of upper thoracic spine on the right side in the 2 h anterior and posterior delayed images [ figure 2 ] . inadequate ascent of tracer over the higher cerebral convexities was noted in the 24 h delayed image [ figure 2 ] . anterior and posterior images of 99 m technetium diethylenetriaminepenta acetic acid cisternography in a patient of spontaneous intracranial hypotension . ( 2a ) 1 h anterior view of lumbar region showed early visualization of both kidneys and bladder ( thin arrows ) . ( 2b ) 2 h anterior view and ( 2c ) 2 h posterior view images showed mild extra - dural radiotracer accumulation in the region of right upper thoracic spine ( dotted arrows ) . ( 2d ) 24 h posterior view image showed inadequate ascent of tracer over the higher cerebral convexities ( notched arrow ) patient started recovering with bed - rest and good hydration , and was discharged after full recovery with conservative management . sih is a rare syndrome with incidence estimated at 5/100,000 per year and a female preponderance . the pathogenesis is considered to be related to csf leak via small dural defects leading to a reduction in csf volume and thus csf pressure . the most common presentation is with a postural headache , which is characteristically exacerbated by upright position and relieved when the patient is recumbent . it may be associated with nausea , vomiting , neck stiffness , horizontal diplopia , blurring of vision , photophobia , field defects , vertigo , tinnitus , dysgeusia , unilateral facial numbness , and weakness . conservative methods like bed rest are the first line treatment . if not effective , interventional methods like autologous epidural blood patch are used . a report suggested that early blind epidural blood patching within one week of onset is effective ; demonstrating complete cure in 77% patients after one ( 57% ) or two ( 20% ) blood patches . csf opening pressure on lumbar puncture is low ( less than 60 mmhg ) or even normal . csf analysis may be normal or show lymphocytic pleocytosis , increased protein content and normal glucose levels . an mri with gadolinium contrast is regarded as a more useful investigation in comparison to a brain ct scan . the mr image appearance in sih is usually diffuse pachymeningeal enhancement limited to the duramater , most likely cause being compensatory dilatation of the dural veins . the leakage site is not easy to detect in a brain mri since the whole spine scan is not available in most cases . it was introduced in 1964 by dichiro and in most of the reported cases it has been shown to be a sensitive tool to detect csf leak , to guide the level of injection of blood patch for leak suppression and to evaluate the therapeutic effect . there are two kinds of findings seen on a rnc done for sih , the direct and the indirect or surrogate signs of csf leakage . the direct sign of leak is diffusion and accumulation of radiotracer into the extra - arachnoid space . the surrogate markers of csf leak include limited ascent of the tracer to the cerebral convexities in most of the cases and early appearance of radiotracer in the bladder suggestive of unusually rapid uptake of the radiotracer into the circulation via the epidural venous plexus . direct evidence of leak is seldom described , perhaps because of the leakage below the limit of resolution of the study . thus , in our case , rnc documented both indirect and direct signs and clearly localized csf leak site in the upper portion of thoracic spine . in conclusion , rnc is an effective method in diagnosing and localizing csf leakage in a case with suspected sih . it is worthwhile applying rnc to evaluate postural headache in patients without a remarkable history of trauma .

spontaneous intracranial hypotension ( sih ) is a cause of new persistent headache , which disappears on recumbence and reappears in sitting / standing position ( orthostatic headache ) . we present a case of orthostatic headache , where the patient was suspected to have sih and was subjected to radionuclide cisternography ( rnc ) using 99 m technetium diethylenetriaminepenta acetic acid for confirmation of diagnosis . after due consent from the patient , the radiotracer was injected intra - thecally and serial images were acquired until 24 h. the direct and indirect evidences of cerebrospinal fluid ( csf ) leakage , which were revealed in our study , provided objective evidence to the clinical diagnosis . rnc is an important investigation in diagnosing sih and also identifying the site of csf leak , which may aid the management .

fibroblast growth factor-23 ( fgf-23 ) is a hormone secreted by the bone cells - osteocytes and osteoblasts . its levels increase as the stage of chronic kidney disease ( ckd ) advances , reaching very high levels in ckd stage 5 . many studies over the last decade have reported fgf-23 as a factor of prognostic significance in ckd . very little data about the significance of this biomarker exists in indian scientific literature and our study report the results of the levels of fgf-23 in stable maintenance hemodialysis patients . all patients who were continuing in our maintenance hemodialysis program in january 2012 were enrolled as a prospective observational cohort . this group was longitudinally followed for 2 years till january 2014 . at the beginning of the study , the demographic profile , native kidney disease , and comorbidities were noted . left ventricular hypertrophy and ischemic heart disease where defined based on standard criteria . the hematochemical parameters and serum fgf-23 levels were tested at the beginning of the study . fgf-23 levels were measured in our biochemistry laboratory using the kit ezhfgf-23 - 32 k human fgf-23 elisa kit ( merck millipore corporation , billerica , ma 01821 , usa ) . it is a colorimetric fluorescent assay . for the analysis of the association of fgf-23 with various studied variables , the levels were divided into two groups ( group i , fgf 23 < 300 pg / ml and group ii fgf-23 300 pg / ml ) . all statistical analysis was performed using the statistical software for windows version 20.0 spss version 20.0 ( ibm corp . no patient dropped out of the study . the mean standard deviation ( sd ) age of 91 patients ( females 34 ) was 60.6 10.8 years . during follow - up , in the next 48 months , five patients were transplanted and are doing well . two patients were shifted to peritoneal dialysis who are also alive and healthy until till the end of the study period . fifty - six of these patients had type 2 diabetes mellitus as the cause of their ckd . the body mass index ( bmi ) of the group is shown in table 1a . body mass index of the cohort the mean sd duration of dialysis in months was 47.2 24.8 months . dialysis details of the cohort the mean sd and the range of the major biochemical and hematological parameters are given in table 2 . serum parathyroid hormone ( pth ) level was consistently high , and the vitamin d level was low in general for the whole cohort . hematological and biochemical parameters of the cohort fgf-23 level was high in the whole cohort . patients with higher fgf-23 levels tend to be older , have higher bmi and on dialysis for a shorter duration [ table 3a ] . association between fibroblast growth factor-23 and demographic , and comorbidity details association of fibroblast growth factor-23 and dialysis there was a strong association between fgf-23 and serum phosphorus levels and pth levels . there was a trend to an inverse relationship with fgf-23 and vitamin d levels [ table 4 ] . a multivariate analysis confirmed the results noted in the univariate analysis [ table 5 ] . association of hematochemical variables and fibroblast growth factor-23 levels multivariate analysis of association between fibroblast growth factor-23and various clinical variables these levels start rising in early stages of ckd and have an exponential increment in levels in stage 5 ckd , especially patients on dialysis . the rise in pth correlated with fgf-23 in ckd patients and this is attributed to the suppressive effect of fgf-23 on vitamin d levels . fgf-23 level was independently associated with a higher risk of myocardial infarction , stroke , coronary , carotid , and lower limb revascularization , lower extremity amputation and death . in some studies , a significantly higher rate of congestive heart failure in patients with higher fgf-23 levels was noted . our study re - emphasizes the strong association between serum phosphorus and pth levels in both univariate and multivariate analyses . simple statistical analyses ( both univariate and multivariate ) did not show any link between fgf-23 and cardiovascular comorbidities ( both the presence of left ventricular hypertrophy and ischemic heart disease ) . the strength of our study is that it is the first of its kind which addresses the issue of fgf-23 levels in relativelyhomogenous stable hemodialysis patients . the limitation of our study is that it is a relatively small study with a short duration ( 2 years ) follow - up . the cohort of patients also is not fully representative of dialysis patients in india as they came from a relatively higher socioeconomic background . our study did not show any link between fgf-23 and cardiovascular morbidity and overall mortality .

fibroblast growth factor-23 ( fgf-23 ) levels start rising early in patients with chronic kidney disease and is implicated in cardiovascular and overall mortality of hemodialysis patients . we conducted a prospective observational cohort study in stable dialysis patients looking into the levels of fgf-23 in hemodialysis patients and its association with various demographic and biochemical variables and mortality . a total of 91 patients were enrolled in the study . the mean fgf-23 levels were very high ( 1152.7 pg / ml ) . fgf-23 levels were significantly associated with serum phosphorus and parathyroid hormone ( pth ) levels in univariate and multivariate analysis . no significant association between fgf-23 and cardiovascular comorbidities and overall mortality was seen . fgf-23 levels rise exponentially in maintenance hemodialysis patients . there is a strong association between fgf-23 and phosphorus and pth levels . no association between fgf-23 and mortality was noted in our patients .

peginterferon alpha-2a ( peg ifn -2a ) is a common treatment for chronic hepatitis b ( chb ) infection . peg ifns are immunomodulatory drugs which can cause many adverse events such as flu - like disease , rash , weight loss and depression . interruption or cessation of peg ifn treatment may sometimes be required due to serious adverse events . during our literature review , we could identify a limited number of reports dealing with vestibular and audiologic adverse effects of peg ifns . in this paper , we present a chb case who developed bilateral ototoxicity during peg ifn -2a treatment which was completely reversible on drug withdrawal . a 41-year - old woman presented to outpatient clinic with complaints of severe fatigue and malaise . her physical examination , past medical history and family history were normal . laboratory values were as follows : complete blood count within normal limits , glucose : 115 mg / dl , bun , creatinine , lipid panel , electrolytes , alkaline phosphatase , gama glutamil transferase and bilirubin levels were all within normal ranges . ast : 16 u / l , alt : 10 u / l , hbsag : positive , hbeag : negative , antihbe : positive and hbv dna : 46.010 iu / ml . abdominal ultrasound showed a single 15 10 mm sized hemangioma in the right lobe of liver and splenomegaly ( 135 mm ) . in liver biopsy with modified ishac scoring system , hepatitis activity index was 5 and fibrosis score was 3 . she was diagnosed with chb and peg ifn -2a 180 g treatment once weekly was iniated . at two month of peg ifn -2a therapy , our patient complained of bilateral tinnitus and hearing loss . at this stage , hbv dna levels were undetectable at first , third and sixth month of treatment but at 6 month , symptoms of tinnitus and hearing loss got worsened and bilateral sensorineural ototoxicity was detected in audiological examination . lamivudine 100 mg once daily was planned whenever hbv dna level exceeds 2000 iu / ml . however , hbv dna remained negative during six month follow - up . she is now symptom free and continues to be followed . audiometry - documented sensorineural hearing loss have been reported during ifn treatment for both chronic hepatitis b and c. ototoxicity tends to become more frequent at doses of more than 100 mu , often develop in the late stage of treatment and reversible when ifn is discontinued early . while hagr et al . , concluded that peg - ifn therapy did not induce ototoxicity , sharifian et al . , and formann et al . , concluded that peg - ifn is associated with ototoxicity and encourage planning hearing monitoring in patients receiving this drug . patterns of hearing loss on interferon may vary and there may not be good correlation between subjective complaints and objective assessment of auditory function . if subjective hearing loss gradually exacerbates , repeat audiometry must be performed with short periods to identify ototoxicity as soon as possible . unilateral and reversible hearing loss in a chb patient due to peg ifn -2a was described in a previous case report , whereas our case developed bilateral and reversible tinnitus and hearing loss during peg ifn -2a treatment . she did not take any other medications that could cause ototoxicity . according to naranjo 's scale , a score of 7 suggested that peg ifn -2a was the probable cause of ototoxicity . many adverse events of peg ifn -2a occurs due to changes or abdormalities in cytokine synthesis . ototoxicity may occur due to direct toxic effect of peg ifns on the ear as well as through otoimmune or hematologic mechanisms . therefore , clinicians must be cautious against the possiblity of ototoxicity in chb patients seeking this treatment .

peginterferon alpha-2a ( peg ifn -2a ) is frequently used in chronic hepatitis b ( chb)treatment . numerous adverse events can be noted during this therapy such as flu - like disease , rash , weight loss and depression . however , peg ifn -2a related ototoxicity seems to be an uncommon entity . ototoxicity can be detected objectively by audiometry . in this paper , we present a case of chb who developed reversible bilateral ototoxicity during peg ifn -2a treatment . due to ototoxicity detected objectively by audiogram , treatment was ceased at sixth month and ototoxicity completely recovered one month after stopping the drug .

the incidence of subcutaneous metastasis from a visceral malignancy , excluding malignant melanoma , lymphoma , and leukemia , is rare with an incidence of 5.3% . skin involvement as the presenting sign of a silent internal malignancy is an even rarer event occurring in approximately 0.8% . we report a rare case of a patient who presented to her dermatologist complaining of rapidly developing subcutaneous nodules which subsequently proved to be metastatic colon cancer , and we provide a review of the literature . a previously healthy 44-year - old caucasian female was referred to dermatology with a 5-week history of rapidly growing subcutaneous nodules on her back , chest , breasts , abdomen , axillae and thighs ( fig . numerous 0.5 - 3-cm , well - defined , mobile , firm and slightly tender subcutaneous nodules without overlying epidermal changes were noted on physical examination . results of a punch biopsy revealed a poorly differentiated adenocarcinoma that was cytokeratin ( ck)-7 negative , ck-20 positive , ttf-1 negative , and cam 5.2 positive , suggestive of metastasis from the lower gastrointestinal tract ( fig . a ct scan was obtained which showed circumferential thickening of the cervix , innumerable subcutaneous masses , sigmoid colonic wall thickening , and extensive retroperitoneal and intra - abdominal adenopathy , with suspicion of metastatic disease ( fig . pelvic examination was unremarkable , but colonoscopy revealed a 4-cm , fungating , non - obstructing sigmoid mass . given the extent of the disease and the lack of obstructive symptoms a tunneled catheter was placed and the patient began systemic therapy with folfox plus bevacizumab . approximately 3 weeks after initiation of systemic therapy the patient presented with bowel perforation and underwent abdominal exploration , sigmoid resection and end - colostomy . at laparotomy a perforated colonic mass was noted with peritoneal disease along the root of the small bowel mesentery without evidence of hepatic metastasis . final pathology returned a poorly differentiated t4 , n2 , m1 adenocarcinoma with signet ring cell and focal mucinous features , and lymphovascular and perineural invasion . subsequent testing revealed the tumor to be wild - type for kras and microsatellite stable . initially , the patient showed improvement in both the number and size of the subcutaneous metastases . however , at the time of her fourth cycle of folfox , some of the lesions began to progress . subsequent ct scan confirmed progression of disease and while folfori plus panitumimab were considered for the patient , she had rapid physical decline , intermittent infections , and therefore only received one dosage of panitumimab before deciding to go home under care of nurses . there is significant variability in reports on the incidence of cutaneous metastasis from visceral primaries , some finding it to be as low as 0.7% , while others find it as high as 9% . retrospectively reviewed 7,316 tumor registry patients and reported an overall 5% incidence of cutaneous metastasis , a number which almost doubled ( 9.6% ) when only patients with known metastatic disease were considered . ninety - two patients ( 1.3% ) presented with cutaneous involvement at the time of diagnosis , 59 ( 0.8% ) of whom had skin involvement as the first presenting sign . of these , 42 ( 71% ) were locoregional metastasis and only 17 ( 29% ) were considered true distant metastases . cutaneous involvement from a colorectal cancer primary accounted for only 18 ( 2.3% ) patients . among these cases , 4 ( 22% ) were present at the time of diagnosis and 3 ( 16% ) were the chief complaint which prompted the search for the primary . the largest meta - analysis to date by krathen et al . , which included both autopsy series and tumor registries ( n = 20,380 ) , reported an incidence of 5.3% ( n = 1,080 ) . the tumor with the highest incidence of cutaneous metastasis by far was breast cancer ( 24% ) , followed by renal ( 4% ) , ovarian ( 3.8% ) , lung ( 3.6% ) , colorectal ( 3.4% ) , and prostate cancer ( 0.7% ) . the most common site for metastasis was the chest ( 28.4% ) , followed by the abdomen ( 20.2% ) , extremities ( 12% ) , neck ( 11% ) , back ( 11% ) , scalp ( 7% ) , pelvis ( 6% ) , and the face ( 5% ) . the identification of cutaneous metastasis from a visceral malignancy is an ominous finding which usually signifies widespread disease and portends a poor prognosis [ 5 , 6 ] . in a retrospective study of 4,020 patients found that after recognition of skin metastases , mean survival ranged from 1 to 34 months depending on the primary tumor . an average survival of 18 months was noted in patients with skin metastasis from colorectal carcinoma . retrospectively reviewed 200 cases of patients with evidence of cutaneous metastasis from a visceral primary and found the median survival to be 6.5 months . patients with an underlying colorectal primary fared even worse with a median survival of 4.4 months . the mechanism of cutaneous metastasis from colorectal cancer is poorly understood but can conceptually be explained . after the initial malignant transformation of colonic mucosal cells , neovascularization occurs , a process fostered by the production of vascular endothelial growth factors , platelet - derived growth factors , and basic fibroblast growth factors . alterations in cell adhesion prompted by a loss of e - cadherin expression allow the malignant cell to interact with the extracellular matrix which it degrades , remodels and subsequently invades . tumor cells attach and migrate along the extracellular matrix via receptor - ligand interactions eventually intravasating lymphatics and venules , facilitating lymphatic and hematogenous metastasis . while once considered a passive course , tumor embolization is now thought to be mediated by lymphangiogenic and angiogenic growth factors which help to increase the total vessel surface area available for invasion , increase the pumping action of draining afferent lymphatic vessels and induce lymphangiogenesis and angiogenesis in preparation for metastasis [ 8 , 9 ] . following intravasation , cells which survive the mechanical stress of circulation and the innate immune system eventually colonize the subcutaneous tissues and lay dormant until they acquire the necessary angiogenic properties , mutations of metastasis virulence genes , or microenvironmental changes which prompt their emergence from dormancy [ 8 , 10 ] . further analysis of the biology of this mode of metastasis may shed light on mechanisms of metastasis to specific organs , and hopefully these findings will provide targets for novel targeted therapeutic intervention .

subcutaneous metastasis from a visceral malignancy is rare with an incidence of 5.3% . skin involvement as the presenting sign of a silent internal malignancy is an even rarer event occurring in approximately 0.8% . we report a case of a patient who presented to her dermatologist complaining of rapidly developing subcutaneous nodules which subsequently proved to be metastatic colon cancer , and we provide a review of the literature .

an 18-day - old baby with failure to thrive was referred to our clinic for eye examination . blood investigations included total and differential blood count , blood sugar , serum electrolytes , serum ammonia , serum lactate , serum pyruvate , liver enzymes , thyroid function tests and arterial blood gases . urine was tested for ph , ketones , odor and reducing substances . karyotyping with g - banding studies was also performed . though all above investigations were within normal range urine gas chromatography showed increased thiamine and uracil levels . fibroblast cultures indicated deletion of the dhpd gene and diagnosis of dhpd deficiency was made . his elder brother was homozygous for the mutation and excreted increased amount of thiamine and uracil in urine ; however , he was clinically asymptomatic . his eldest sister has two normal alleles but his mother was heterozygous for the condition . subsequent follow - up his vision was found to be reduced to 20/100 ( cardiff acuity cards ) . ophthalmic examination under general anesthesia was essentially normal apart from astigmatism in both eyes . glasses were prescribed with orthoptic follow - up . at the age of six years his visual acuities deteriorated to 20/200 and 20/120 ( sheridan gardner ) in the right and left eye respectively . however , on subsequent follow - up , he was found to have markedly reduced corneal sensations and a revised diagnosis of neurotrophic keratitis was made . for the last three years his vision has remained unchanged and his eyes have been managed satisfactorily with ocular lubricants with no further recurrence of the corneal epithelial defects [ fig . 2 ] . the dhpd enzyme is the rate - limiting step in the metabolism of pyrimidine bases.3 it catalyses the first step in the conversion of thymine and uracil to beta - aminobutyric acid and beta- alanine respectively [ fig . partial or total deficiency leads to increased accumulation of thymine and uracil in the serum as well as cerebrospinal fluid . it has been postulated that the dhpd enzyme is required for the synthesis of beta alanine , which is a neurotransmitter in the brain . this may explain the reduced corneal sensation and the development of neurotrophic keratitis in this child . various manifestations associated with dhpd deficiency have been described , but most children present with microcephaly , epilepsy and abnormal eeg profile , however , many may be asymptomatic.4 ocular manifestations such as microphthalmia , choroidal coloboma and nystagmus have also been reported.2 the condition has attracted interest in the recent years as the dhpd enzyme is also the initial step for the metabolism of widely used anti - neoplastic drug 5 fluorouracil . severe toxicity , including death , following administration of 5 fluorouracil was reported in patients with dhpd.3

we describe a case of neurotrophic keratitis in association with dihydroxypyrimidine dehydrogenase ( dhpd ) deficiency . ocular manifestations in patients with dhpd are rare and neurotrophic keratitis has never been reported before . a six - year- old boy who was a known case of dhpd deficiency and born of a consanguineous marriage presented to our clinic with non- healing corneal ulcers in both eyes . reduced corneal sensations were detected and the patient was started on lubricating eye drops . the patient continues to be on lubricant eye drops and there has been no recurrence of the disease .

synovial sarcoma ( ss ) is a highly malignant tumor that occurs mainly in adolescents and young adults and is usually seen in the extremities . however , primary synovial sarcoma arising from the lung is extremely rare , accounting for 0.3% to 1.3% . it is closely associated with smoking . besides clinical evaluation and imaging methods for definitive diagnosis , immunohistochemical examination is needed . a 69-year - old man was admitted to the hospital with right - sided chest pain . the patient was a heavy smoker with a history of smoking 120 packs / yr . computed tomography ( ct ) of the chest revealed a 605670 mm mass lesion invading the right upper and middle lobes and extending to the mediastinum and the chest wall ( fig . tru - cut biopsy was taken from the lesion , and histological examination was suspicious about malignancy . positron emission tomography / ct detected an increased f18-fluorodeoxyglucose uptake ( maximum standardized uptake value , 8.2 ) only in the mass . surgical exploration was decided upon , and right bilobectomy superior bronchoplasty with mediastinal lymph node dissection was performed . the lobectomy material was 20115.5 cm in diameter , and macroscopic examination revealed an 11-cm , well - demarcated , brownish , necrotic mass in continuity with the bronchial tree and adjacent to the pleura ( fig . histopathological examination showed long bundles of spindle cells with no pleomorphism and gland - like structures including single - row epithelium , to be more prevalent in the tumor periphery ( fig . the spindle cells were positive for b - cell lymphoma 2 ( bcl-2 ) in the scattered foci and negative for cd99 , wilm s tumor-1 , actin , caldesmon , cd34 , s-100 , pan - cytokeratin , and endomysial antibodies ( ema ) ( fig . the epithelium of gland - like structures was positive for ema and pan - cytokeratin ( fig . the epithelial groups at the periphery of the tumor were positive for thyroid transcription factor 1 . as a result of morphological and immunohistochemical findings , spindle cell ss ( biphasic type ) was diagnosed . following surgery , we planned 4 cycles of adjuvant chemotherapy followed by radiotherapy . he received 4 cycles of adjuvant chemotherapy and then completed the courses of radiotherapy on june 2013 . it accounts for 10% of all soft - tissue sarcomas and is slightly more common in men . four histologic subtypes are described : biphasic , monophasic ( spindle ) , monophasic epithelial , and poorly differentiated ( round cell ) tumor . the biphasic subtype is easily diagnosed on the basis of the presence of both epithelial and spindle cells . monophasic subtype can be mixed up with other types of sarcoma , and therefore , immunohistochemistry is essential for differential diagnosis . our case was characterized by sarcoma composed of spindle cells and epithelial cells on histopathological examination ; epithelial cells were positive for ema and pan - cytokeratin , and spindle cells were positive for bcl-2 . although the cytomorphologic and immunohistochemical features of ss are sufficiently characteristic for diagnosis , clinical correlation is also essential for an accurate diagnosis of primary ss of the lung . in our case , the diagnosis of the primary ss of the lung was also based on the absence of the tumor at any other site of the body . both monophasic and biphasic forms are characterized by a reciprocal chromosomal translocation ( x ; 18 ) ( p11.2 ; q11.2 ) which results from the fusion of the syt gene on chromosome 18 to either of two genes , ssx1 and ssx2 in the region xp11 . despite its high sensitivity , molecular testing is not essential for the diagnosis of ss . in our case , molecular testing was not performed due to the certain diagnosis of ss on the basis of clinical , histological , and immunohistochemical findings . sixty six percent of primary pulmonary ss are centrally located and present with obstructive pneumonia , hemoptysis , dyspnea , cough , and fever . ss can also arise from the pleura . however , primary ss of the pleura is also very rare and there are a limited number of reported cases . the tumor was adjacent to the pleura , but there was no pleural involvement microscopically . prior to surgery , the primary focus of ss or metastasis should be excluded by imaging procedures . our patient underwent right bilobectomy and mediastinal lymph node dissection and then , received four cycles of adjuvant chemotherapy and radiotherapy postoperatively . in conclusion ,

synovial sarcoma ( ss ) is a highly malignant tumor that accounts for 10% of all soft - tissue sarcomas . primary ss arising from the lung is extremely rare , and the prognosis is poor . we report a case of pulmonary ss presenting with a mass lesion invading the right upper and middle lobes , extending to the mediastinum and the chest wall . after tru - cut biopsy , surgical resection was performed . the final diagnosis was ss ( biphasic type ) based on histological and immunohistochemical findings . there are no guidelines for optimal treatment due to the rarity of these tumors . current treatment includes surgery and adjuvant chemotherapy and/or radiotherapy .

central venous catheter ( cvc)-related bloodstream infection is associated with significant mortality and morbidity in critically ill patients , much of the focus , however , has remained on the bacterial pathogens . catheter - associated mycobacteremia is a rare entity , even in oncology patients undergoing chemotherapy via a totally implanted central venous device ( tid ) , its diagnosis starts with disbelief and is followed up with enormous diagnostic and clinical challenge . it stares the clinician with the myriad treatment options antimicrobial regimen , duration of therapy , and cvc management , remains unclear . they are ubiquitous in nature and can be found in soil , bioaerosols ; they are known to form biofilms in lungs , a property conducive to colonizing central venous device ( tid ) and subsequently causing infections . a 48-year - old diabetic female was admitted to our hospital with a history of fever with chills for past 10 days . a known case of carcinoma caecum thereafter she was put on chemotherapy regimen folfox ( folinic acid ) , fluorouracil ( 5-fu ) and oxaliplatin of which she has already received three cycles . her total leukocyte count ( tlc ) was 2.5 10/l , differential leukocytes count - n45 , l50 , and m5 . a provisional diagnosis of febrile neutropenia was made , and growth factor was given following which tlc increased , but the fever still persisted . an echocardiography was confirmatory . to rule out fever due to embolization prothrombin time and international normalized ratio so , a full - fledged fever work up was done , in view of the immunocompromised state of the patient . all the tests , urine r / e , urine culture , malarial antigen , dengue ns1 and igm , widal , anti hav igm , anti hev igm , cytomegalovirus igm , anti epstein barr virus ( viral capsid antigen ) igm , anti - herpes simplex virus ( 1 and 2 ) igm ; were negative . blood cultures were also sent , on 4 day the blood sample which was taken from the chemo port flashed positive in bactalert , a gram - stain revealed irregularly staining gram - positive bacilli [ figure 1 ] . an erlich - ziehl - neelsen stain was done , and acid - fast bacilli were seen [ figure 2 ] . subcultures were done on blood agar , macconkey agar without crystal violet , lj media , middlebrook 7h9 broth in mycobacteria growth indicator tube . gram - stain from blood culture ziehl neelsen stain blood culture three days later pale and opaque colonies grew on blood agar , which acquired yellowish - pink tinge on further incubation [ figure 3 ] . mycobacterium fortuitum on blood agar upon the suspicion of a rapidly growing nontuberculous mycobacterium ( rgm ) spp . the isolate was was sent to a reference nabl accredited private lab for further speciation , where it was identified as m. fortuitum . the patient had a past history of tuberculosis for which she had completed treatment ( 25 years back ) . however , the current illness seemed unrelated to it . to search for an active focus of tuberculosis , however , chest high - resolution computed tomography did not show active lesion or cavity . erlich - ziehl - neelsen stained sputum and urine were negative for acid fast bacilli . therefore , pulmonologist 's consultation was taken , and anti - tuberculous therapy ( att ) was started . as the patient was discharged and advised to be followed up in out - patient department with a baseline liver function test to monitor att related toxicity . this time chemotherapy was given via a peripheral line , as a matter of caution to prevent the possible impending bacteremia . on the 4 day the chemo port cultures were positive again for acid fast bacilli . the diagnosis of chemo port colonization was made and removal of chemo port was planned . although rgm are not highly virulent or life threatening , they have a high predisposition to create biofilms and thus to colonize and infect intravascular catheters . catheter - related rgm infection nearly always , occur in patients who have a cvc in situ , in a 10 years review of oncology patients , gil et al . reported that cvc was present at diagnosis in 136 ( 97% ) of 140 patients , the underlying malignancies were commonly hematologic . pediatric and male patients were more predisposed ; chemotherapy , corticosteroids , and lymphopenia were other important risk factors . fever with or without chills and rigors in a patient who has received chemotherapy via a tid / cvc in the past 3 months is a subtle indicator of the underlying infection . paired blood cultures should be drawn from the catheter site as well as periphery and send in bactec or bactalert bottles for continuous monitoring of blood cultures . although insertion site is usually normal , redness or oozing at the catheter exit site is a proclamation of an infection underneath . therefore in such cases a tip off should be sent to the microbiologist to look out for non - tuberculous acid - fast bacilli in the background of patient 's history and a negative gram - stain . cutaneous abscess and catheter hubs should also be cultured for mycobacteria . auramine - rhodamine staining and nucleic acid assays prognosis is excellent when removal of catheter is done in addition to administration of systemic antibiotics . most commonly used antibiotics are amikacin , clarithromycin , linezolid , cotrimoxazole , and ciprofloxacin . species identification should always be attempted as response to amikacin , clarithromycin , linezolid , cotrimoxazole and ciprofloxacin may vary with species . in 96% of the patients the optimum duration of treatment is 4 weeks , longer treatment offers no additional benefit however , treatment has to be individualized as no guidelines are currently available . outbreaks of bacteremia from oncology units and subsequent isolation from the tap and municipal water have been reported . therefore , patients should be advised to cover the catheter sites while taking a bath . in hospitals catheter care clinicians need to be aware of the significance of nontuberculous mycobacteria ( ntm ) infections in immunocompromised patients with tids which are usually present for long times and in the event of fever , blood cultures can enhance detection of such infections . ntm infections are also underreported in the laboratory as aerobic blood cultures are usually sent and many times gram - positive bacilli may be dismissed as diphtheroids and not processed further for identification .

mycobacterium fortuitum is a rapidly growing mycobacterium ubiquitous in nature , known to form biofilms . this property increases its propensity to colonize the in situ central line and makes it a prospective threat for nosocomial infection . we report a case of 48-year - old female with carcinoma cecum who reported to us with clinical illness and neutropenia while on chemotherapy via totally implanted central venous device , postlaparoscopic - assisted right hemicolectomy .

new technological innovations have contributed to profound changes in the quality of life of human beings and societal changes . while each job has its own stress , the fast and relentless pace of technology - enhanced work environment in it has created new culture . two healthy software engineers subjected themselves willfully for repeated snake bite and gained access to snake venom , so as to get relieved of their stress . this is reported in order to create awareness of such issues among emergency physicians and practitioners . there were three reported cases of snake venom use in psychoactive substance users to experience there are few cases of such addiction to semipoisonous snakes like rat snake and green wine , reported in the local press . however , to our knowledge , this is the first report of willful exposure to snake venom from direct bite for the purpose of mental relaxation among nonusers of illicit drugs and without any underlying psychiatric disorders . a 25-year - old software engineer came to emergency department ( ed ) , with a request to get himself tested for hiv infection , even though he did not have any previous episodes of unprotected sexual intercourse or any illicit drug use . however , he said that he has subjected himself willfully to repeated snake bite over a period of 6 months with an interval of 30 - 45 days between each exposure . patient was questioned on the awareness of toxic effects of snake venom and he had optimal knowledge . incidentally , he said that he was stressed very much and had insomnia , due to immense work pressure . as some of his colleagues exposed to snake bite willfully felt relieved of his stress and experienced euphoria , patient accepted for willful snake bite and felt relaxed and had good sleep also . with patient 's consent , he was investigated for hiv and after this episode another friend of primary case , who is also a software engineer of 23 years old , came to ed with same request , as he has subjected himself to willful snake bite . he experienced sound sleep for 20 - 24 h and had relaxed mind after snake bite without any hang over / head ache , tremor , and sense of crawling . interestingly , these two cases informed that there are different dens in different cities wherein people who want to have snake bite are allowed to sit in chairs . the person in charge of snakes holds the snake near the head end of snake just distal to lip margin . initially , he makes the snake to inject minimal bite in little toe or index finger for minimal envenomation , and then , he makes the snake to bite in lip or tongue of individuals according to their wish . persons who were bitten , showed jerky movement and left the room within few minutes . from the reports many people who use such dens were from high socioeconomic status and well educated . some of them were youth and college students . ancient cultures all over the world believe that repeated snake bites / snake venom inoculation renders a person immune to fatal snake envenomation . tribal regions even in india are known to give snake bites purposefully to their children in order to protect them from fatal complications of snake bite . lack of symptoms in our reported cases and in these primitive practices may be due to injection of too little venom , precisely the quantity needed for recreational purpose / immunity which needs further exploration . multiple factors like easy availability , adventure seeking , social / peer - pressure , novel sensation , pain relief , and cultural beliefs might have influenced the use of snake bite as a form of substance abuse . moreover , snakes form an important part of hindu mythology and are worshipped even today , thereby general population being unafraid of them . during middle age period , physicians used snake venom of various snakes as medicinal agents . base on observations , we hypothesized the mechanism and uses of snake venom in clinical medicine . snake venoms have antinociceptive and analgesic activity , and certain isolated neurotoxins have demonstrated significant analgesia in animal models . the venom on entering human blood releases active metabolites such as serotonin , bradykinin , peptides , prostaglandins , and other slow reacting substances . drowsiness was the most common symptom observed among cobra bite , which may be due to effect of toxin in brain . literature review showed that in individuals injected with cobra venom , had marked relief of pain in nearly 65% of the patients and a mild - to - moderate relief in more than 80% , and the site of analgesic action being peripheral and central nervous system . also , long - form alpha - neurotoxin from cobra venom produces a potent opioid - independent analgesic effect by acting on nicotinic acetyl choline receptors ( nachrs ) . cobra venom resembles to the action of morphine but differs from the opiate in that it does not produce addiction and other disagreeable or dangerous by effects . there is a debate in the fatality / immunity due to repeated snake bites in human beings either accidentally or incidentally . haast and winer reported complete recovery of a patient without any specific therapy even after bitten by a deadly snake bangarus caeruleus and the authors attributed it to cross protection of existing antibody between species of bangarus and indian , african and egyptian cobras , as he had a history of bites from these snakes earlier . repeated poisonous snakes bites , though believed to render the individuals immune and reduce fatality of subsequent bites , parrish and pollard analyzed the effect of repeated bites in 14 patients and concluded that bites from pit viper did not produce any kind of immunity and can cause death due to anaphylaxis . limitation of this report is that the nature of snakes involved for willful snake bite could not be verified . also , recall bias of the individuals has to be considered while interpreting patient 's statements . physicians and practitioners have to be aware of novel methods and more research is warranted in this field both for prevention as abuse and exploration of newer therapeutic molecules from snake venom .

snake venom use for recreational purposes has been documented earlier . willfully subjecting oneself to repeated lethal snake bite as a source of getting relieved of stress and recreation observed in two healthy software engineers , without any underlying psychiatric ailments or comorbidities along with probable mechanisms , are reported . emergency physicians and practitioners have to be aware of novel methods of exposure to snake venom so as to recognize such cases and treat them accordingly .

monocondylar tibia plateau fractures with non - comminuted fragments can be treated using percutaneous screws . currently indirect methods of reduction are used and thus the technique is limited to fragments with less than 5 mm depression . the first author has designed a device for direct elevation and reduction of the fragments thus potentially expanding the indications of percutaneous screws to fragments with > 5 mm depression a total of ten cases were treated by this method of percutaneous elevation of the depressed fractures of lateral condyles of the tibia using this device . the inner piston of the device in slowly hammered inside thus elevating the depressed fragment . the new device is able to elevate unicondylar tibia plateau fragments with no subsidence or loss of fixation in our series . a longer follow up in a larger sample will be needed to establish the technique . the tibial plateau fractures are still a challenging problem and demand an aggressive management as any other intraarticular fractures of the joints . before the advent of the recent advances conservative management was the treatment of choice resulting in joint stiffness which was very crippling to the patient . the thorough understanding of the classification the tibial plateau fractures based on the recent investigations , has opened the gates for better management . the amount of depression and the displacement of the condylar fractures , articular incongruity can be well assessed nowadays . schatzker classification is the most accepted classification currently and type i to iv fractures are associated with angulated or depressed fractures of either of the one condyle . in cases with large sinlge peripheral fractures most papers describe indirect method of reduction of these fragments via ligamentotaxis and thus limit themselves to depression < 5 mm . we designed a new device to achieve direct elevation of these fragments and thus use the percutaneous technique in depression > 5 mm . the present paper discusses the usefulness of the device in elevation of the depressed condyles with a small window ( very minimal incision ) . device : the device is designed by first author [ vsr ] indigenously with 316 ss alloy . the diameter of outer sleeve is 11 mm and the wall thickness of the sleeve is 1 mm . the diameter of the solid piston is 10 mm and it freely moves to and fro in the outer sleeve ( fig . the serrated edges of the sleeve help in insertion in the metaphyseal area surgical steps : ten male patients ( age between 25 - 40 years ) were operated using this device . first the direction elevation was assessed by a guide wire passed through a drill hole on the antero medial aspect of the upper one fourth of the tibial metaphysis ( fig . a bone window sufficient to accommodate the outer sleeve is made round the guide wire . then the piston was pushed into the sleeve and the piston was tapped towards the depressed fracture carrying a cylindrical cancellous plug of the bone to elevate the fracture condyle till plateau is congruous which was checked under the c - arm image in both views ( fig . next again under c - arm control a guide was passed perpendicular to the fracture line of the condyle keeping the piston in the intramedulary canal . a cancellous screw was threaded over the guide wire to fix the fracture ( fig . we had used two screws in majority of the cases with one screw used in one case , depending on size of the fragment . we were able to achieve good articular reduction in all our cases by use of this technique . weight bearing was allowed after the radiological union was present i.e after 8 weeks . in this buttressing with a plate was not needed as we felt the fixation achieve was stable enough and also weight bearing was delayed allowing for healing of the fracture . early results are encouraging with all cases achieving radiological union and good knee range of motion . there were no cases of loss of reduction or any other complications although a longer and more detailed prospective follow up will be required to establish the potential clinical importance of the device after elevation of the fragment another guidewire is passed through the fragment over which a 6 mm cannulated cancellous screw is passed percutaneously - d . percutaneous screw fixation in cases on monocondylar tibia fractures will prevent the morbidity associated with open procedure and is less expensive too . a lot of case series describe percutaneous screw fixation however these are based on indirect reduction techniques and are limited to depression less than 5 mm [ 1 - 6 ] . we felt a device which can directly help in elevating the fragment to achieve intraarticular reduction will definitely expand the indication of this minimally invasive technique . the solid inner rod compresses the metaphyseal cancellous bone thus compacting it below the subchondral area . we found this technique to be useful in 10 of our patients to achieve reduction . however most of our patients were young and were operated within a day or two of injury , thus usefulness of this device in older injuries and older patients ( with osteoporosis ) is yet to be defined . a long term follow up , a larger size sample and report of reproducability of this device by our peers will be essential to confirm the potential usefullness of this device .

introduction : monocondylar tibia plateau fractures with non - comminuted fragments can be treated using percutaneous screws . currently indirect methods of reduction are used and thus the technique is limited to fragments with less than 5 mm depression . the first author has designed a device for direct elevation and reduction of the fragments thus potentially expanding the indications of percutaneous screws to fragments with > 5 mm depressiontechnical note : a total of ten cases were treated by this method of percutaneous elevation of the depressed fractures of lateral condyles of the tibia using this device . device was inserted through a bony window on the anteromedial surface of tibia . the inner piston of the device in slowly hammered inside thus elevating the depressed fragment . elevation of fragment could be achieved in all the cases . the fractures were fixed with cancellous screws applied percutaneously . there were no cases with loss of fixation or subsidence of the fragment . all cases achieved radiological union and have good knee function at follow upconclusion : the new device is able to elevate unicondylar tibia plateau fragments with no subsidence or loss of fixation in our series . a longer follow up in a larger sample will be needed to establish the technique .

dipeptidyl peptidase-4 inhibitors ( gliptins ) are effective drugs in management of type 2 diabetes mellitus ( dm ) . there are reports implicating them in causing acute pancreatitis , chronic pancreatitis , and pancreatic duct metaplasia ; leading to widespread concern . although gliptins are increasingly being used in clinical practice , data on incidence of acute pancreatitis with this class of drug is lacking from our country . we evaluated the extent of this adverse effect in patients on gliptins on our follow - up . this study was conducted as a prospective , observational study in a tertiary care hospital setting . patients with type 2 dm receiving one of the gliptins ( sitagliptin , vildagliptin , or saxagliptin ) for at least 1 month during the study period january 2012-june 2013 were included in the study . equivalent doses of these three gliptins were used interchangeably during the period of the study depending on their availability in the hospital pharmacy . detailed history regarding gall stone disease , pancreatitis , alcohol abuse , and drug use was obtained . five of them had history of acute pancreatitis ( all mild ) > 6 months prior to inclusion which had completely resolved with no residual pseudocyst or chronic pancreatitis . during that episode , these patients were not on treatment with gliptins . in addition to testing fasting and postprandial glycemia ; lipid profile , liver and kidney function test , serum amylase , and ultrasonography ( usg ) of abdomen was done focused at gall stone / sludge , pancreatic morphology , and calcification . all other tests were done as laid down in relevant guidelines for type 2 dm during follow - up . patients were explained regarding symptoms of acute pancreatitis ( abdominal pain , nausea , and vomiting ) and asked to report immediately to nearest medical help if it occurred . acute pancreatitis was diagnosed based on raised serum amylase levels > 3 upper limit of normal ( uln ) with or without ultrasonographic changes in a patients with symptoms suggestive of acute pancreatitis . in asymptomatic patients , serum amylase and usg abdomen was performed every 3 months to exclude silent acute / chronic pancreatitis . patients with history of gall stone disease , chronic pancreatitis , alcohol abuse ( > 10 g daily ) , consuming drugs known to cause pancreatitis ( glucocorticoids , antiretroviral therapy , azathioprine , valproic acid , furosemide , etc . ) , and hypertriglyceridemia ( triglyceride > 1,000 mg / dl ) were excluded . patients who developed acute pancreatitis were withdrawn from the study , gliptins were discontinued and they were managed on the standard lines for acute pancreatitis based on its severity . a total of 216 patients with type 2 dm on treatment with one of the gliptins for at least 1 month prior to inclusion in the study were seen during the period of the study . thirty - one patients were excluded based on the set exclusion criteria ( gallbladder stone / sludge in 15 , alcohol abuse in nine , drug use in five , and triglyceride levels > 1,000 mg / dl in two patients ) . of the remaining 185 patients who were included , 26 were obese ( body mass index ( bmi ) 25 kg / m ) and 43 overweight ( bmi : 23 - 24.9 kg / m ) . total follow - up during the study period ( number of monthly visits number of patients ) was 2,464 patient - months ( 205.3 patient - years ) . total duration of gliptin use varied from 1 month to 4 years in these patients ( median usage 22 months ) . during the study period , one patient ( 0.48 per 100 patient - years ) presented with acute abdomen with raised amylase levels in diagnostic range for acute pancreatitis . asymptomatic elevation of serum amylase > 3 uln was noted in five patients ( 2.4 per 100 patient years ) , without any sonological evidence of pancreatitis , which resolved within 3 days of withdrawal of gliptins . as the three available gliptins were used interchangeably by patients during the study period , no particular drug could be implicated in the causation of this adverse effect . in this observational study , we noted one patient with acute pancreatitis ( an incidence of 0.48 per 100 patient - years ) which was mild and self - limiting on drug withdrawal . during the same period , incidence of acute pancreatitis in general population is reported to be around 1.9 per 1,000 patient years and is known to occur at a greater frequency in patients with diabetes ( 5.6 per 1,000 patient years ) . this risk has been shown to be similar or up to six - folds higher in various observational studies with glucagon - like peptide 1 based therapies . although drug - induced pancreatitis can occur at any duration of exposure , more than half of gliptin associated acute pancreatitis has been reported to occur in the first month of exposure . gliptins are also implicated in causing silent chronic pancreatitis , but none was noted in our patients during the period of follow - up . the limitations of this study are patient self - reporting of symptoms of acute pancreatitis , which often may be mild and ignored by the patient . alcohol abuse of even less than the exclusion criteria used in this study may cause or contribute to acute pancreatitis . only usg was used for imaging of the pancreas due to ease of performing and safety although ct scan is a better modality for pancreatic imaging . amylase levels return to baseline within 48 h of onset of symptoms , hence delayed presentation may have led to a false negative normal amylase . more patients with asymptomatic hyperamylasemia might have been missed as screening was done quarterly . to the best of our knowledge , this is first report of incidence of acute pancreatitis with use of gliptins from india . larger prospective database with a diabetic and nondiabetic control population is likely to shed more light on this issue . acute pancreatitis is well known to occur at a greater frequency in patients with type 2 dm . the heightened risk of this dreaded disease is suspected with the use of gliptins . in this small study with its limitations , we did not note any greater risk of acute pancreatitis than expected in a cohort of type 2 dm patients . however , greater watchfulness for this dreaded adverse effect and avoidance of its usage in patients at high risk for pancreatitis is a prudent approach .

there are reports of acute pancreatitis with the use of dipeptidyl peptidase-4 inhibitors ( gliptins ) . this class of drugs is widely being prescribed for type 2 diabetes mellitus ( dm ) in our country . we evaluated the incidence of acute pancreatitis with the use of gliptins during the period january 2012-june 2013 . patients of type 2 dm on treatment with any of the gliptins ( sitagliptin , vildagliptin , or saxagliptin ) for at least 1 month duration were included . a total of 185 patients were included ( 205.3 patient years of follow - up ) . five of them had history of acute pancreatitis ( all mild ) > 6 months prior to inclusion with complete resolution and no chronic pancreatitis . one patient ( 0.48 per 100 patient years ) presented with mild acute pancreatitis which resolved in 8 days . asymptomatic elevation of serum amylase > 3 upper limit of normal was noted in five patients ( 2.4 per 100 patient years ) , without any sonological evidence of pancreatitis , which resolved on withdrawal of gliptins . none of the patients with previous history of pancreatitis had a recurrence of pancreatitis . in a group at low risk of acute pancreatitis , incidence of acute pancreatitis is low with the use of gliptins .

we did a single - center retrospective analysis of seven patients with pelvic abscess treated by eus transrectal drainage between january 2010 and august 2014 . there were four men and three women , with a median age of 50 years ( range 22 - 68 ) . a concomitant intravenous antibiotic treatment was always administered be for eus and for a minimum of 7 days after drainage . the method of drainage was done with a linear interventional echoendoscope ( pentax ) ( eg 3870utk pentax - hitachi , hambourg , germany ) . eus - doppler evaluation was first performed to exclude the presence of intercalated blood vessels before puncture with a 19-gauge access needle ( cook ) ( 19 g , echotip access needle , cook ireland ltd . , limerick , ireland ) . the puncture tract was then enlarged with a 10 french diathermic cystostomy over a tetrafluoroethylene ( tfe)-coated 0.035-inch guidewire ( cook endoscopy , winston - salem , nc , usa ) . a second guidewire was then put into the cavity , and two 7 french double pigtail plastic stents were positioned ( 4 or 7 cm length ) . eus drainages were done for a majority of abscesses post surgery ( n = 5/7 ) . the treatment was feasible and effective in 100% of cases [ figures 17 ] , without supplementary radiological or surgical intervention [ table 1 ] . the median time of hospitalization was 10 days ( range 4 - 25 days ) . the main difficulty related to this technique is the positioning of the double pigtail plastic stents , induced by pus outflow that can reduce the endoscopic visibility . two of our patients were embarrassed by the length of the double pigtail plastic stents which protruded in the anal canal . pelvic abscess before drainages pelvic abscess after drainage sagittal view of pigtail stent in pelvic abscess fluoroscopic view of first pigtail insertion endoscopic ultrasound ( eus ) view of douglas abscess eus view of abscess puncture endoscopic view with first guidewire insertion etiology and outcomes since 2003 , eus pelvic abscesses drainage is performed ; given the proximity between the rectal lumen and the abscess , with a mini - invasive technique compare to radiological or surgical drainage . moreover , percutaneous drainage may be difficult to realize and uncomfortable , especially if the collection is in deep location which needs a posterior drainage . our technique is safe , without adverse events observed ; and is actually well standardized , in analogy with 10 years of practice for eus drainage of pancreatic pseudocysts . the use of the fluoroscopy and cystostomy facilitates the procedure and can be easily used by experienced operators . the length of double pigtail plastic stents should be as short as possible , especially if drainage is done in the lower rectum , because it may cause discomfort if it touches the anal canal . we can also conceive that the length of hospital stay could be further reduced if the antibiotic treatment is continued orally in selected patients . eus transrectal drainage is a safe and an efficient method for therapeutical treatment of pelvic abscess . in our experience , we recommend eus transrectal drainage for pelvic abscess as the first - line technique for experienced hands .

background and objective : pelvic abscesses are a well - known complication of intestinal diseases or abdominal surgery . we report our case series concerning transrectal drainage by endoscopic ultrasound ( eus).methods : between january 2010 and august 2014 , seven patients received transrectal drainage by endoscopic ultrasound ( eus ) were selected and analyzed.results:two pigtails was positioned under fluoroscopic and eus control . the success rate was 100% and complication rate was 0% . the median time of hospitalization was 10 days [ range 4 - 25].conclusions : the technique appears to be safe and feasible in all etiologies . in our experience , we can considerate transrectal drainage by eus like a first - line technique in experienced hands .

the mainstay of any ovarian cancer therapy is a cytoreductive surgery , with optimal reduction the desirable outcome or with suboptimal reduction the achievable outcome . however , some patients presents in advanced stage , poor general condition and with mucinous histology . there is a wide range of therapeutic challenges and dilemmas in managing these patients . here we present a case of advanced ovarian mucinous cystadenocarcinoma with pseudomyxoma peritonei who was considered to be inoperable in view of her clinical finding and computed therapy scan finding in consultation with oncologist and surgeon . the patient subsequently underwent cytoreductive debulking surgery in a palliative approach and had significant improvement in symptoms . a 58-year - old postmenopausal female ( p9l9 ) patient presented to gynae outpatient department with progressive distension of abdomen for 6 months . she had no bowel or bladder complains . on examination , vitals were stable , there was slight pallor , and no lymphadenopathy . on per abdominal examination , abdomen was uniformly distended , but fluid thrill was not elicited . no definite mass was palpable . on per speculum examination , the cervix and vagina were healthy . on per vaginal examination , the uterine size and adnexal mass could not be well appreciated due to tense ascites . the complete blood count , liver function test , kidney function test were within normal limit . magnetic resonance imaging abdomen showed ascites , large bilateral multiloculated adenexal mass with a large sheet of omental cake . usg guided fine - needle aspiration cytology from the ovarian mass was suggestive of mucinous adeenocarcinoma of the ovary . based on above findings , a diagnosis of advanced nonresectable ovarian cancer was established and collective decision made by gynecologist , oncologist and surgeon to start the patient on primary neoadjuvant chemotherapy . however , the patient did not respond well to chemotherapy and was taken for cytoreductive surgery . intraoperatively , approximately 5 l of thick mucinous material was removed [ figure 1 ] . the bilateral ovarian tumor [ figure 2 ] and the omental cake [ figure 3 ] were removed . the uterus , bladder , bowel were extensively studded and there was loss of plane between uterus and bladder , so hysterectomy was not done . this case is being reported to highlight the therapeutic dilemmas in the management of an advanced mucinous ovarian cancer . the standard initial treatment of patients with advanced ovarian cancer is cytoreductive surgery , followed by combination chemotherapy with paclitaxel and a platinum agent . however , despite the advances in surgery and chemotherapy , the overall 5-year survival rate remains quite low . this is mainly attributed to the fact that patients usually present with advanced stage disease as well as to the lack of effective therapies . in advanced epithelial ovarian cancer , the aim is complete cytoreduction of all macroscopic visible disease , since this has been shown to be associated with a significantly increased overall survival and progression - free survival . a recent meta - analysis of more than 3000 patients evaluating the surgical outcome in ovarian cancer showed that residual tumor is a more powerful prognostic determinant than federation of gynecology and obstetrics stage . a large prospective trial showed that in advanced bulky stage iiic or iv disease , three cycles of platinum - based neoadjuvant chemotherapy followed by interval debulking surgery was not inferior to primary debulking surgery followed by chemotherapy . as a result of these data , the use of primary chemotherapy with interval surgery is becoming more widely accepted . however , the dilemma and challenge for the surgeon is that improper assessment about the operability of the case may lead to open and shut situation and cause further deterioration of the patient 's condition . we faced similar dilemma for the index case while choosing for primary debulking surgery verses neoadjuvant chemotherapy and subsequently it was planned for neoadjuvant chemotherapy . however , it has been shown in a few series that advanced mucinous ovarian carcinoma has a poor outcome with a significantly worse survival . the standard chemotherapy regimen used in advanced ovarian carcinoma comprises of paclitaxel and platinum agents , but in mucinous tumors of the ovary , these agents have inferior response rates due to inherent chemoresistance . this might be the reason for inferior response in the index case to neoadjuvant chemotherapy . the recent studies suggests the role of oxaliplatin and 5fu in the management of mucinous tumors of the ovary because of its biological similarity with cancer of colon . the quality of life of the patients in advanced mucinous tumors of the ovary deteriorates with non - response to chemotherapy and gradual progression of the disease . due to poor response to chemotherapy , these patients often have distressing symptoms in form of huge abdominal distension , thick mucinous ascites not amenable to routine abdominal paracentesis , respiratory distress , constipation and decreased appetite . as the thick mucinous ascites is difficult to aspirate with routine abdominal paracentesis , a thick bore needle is required for aspiration but the maximum benefit from all these distressing symptoms can be achieved from removal of mucinous ascites and maximal surgical debulking . the index case had significant relief postsurgery and her quality of life has improved significantly . there is an increased focus on treatment of these patients with a new strategy combining maximal cytoreductive surgery with maximal regional chemotherapy ( hyperthermic intraperitoneal chemotherapy , hipec ) . hipec combines the direct effects of hyperthermia against the cancer cells with the effects of locoregional chemotherapy . hyperthermia has been known to have direct cytotoxic effects in both temperature and time - dependent manner with a greater depth of penetration of the chemotherapy agents into the tumors . in addition , heat synergizes the cytotoxic drugs selected for intraperitoneal use at the time of surgery . advanced mucinous tumors of ovary is a separate entity and has different biological behavior and drug sensitivity . palliatve cytoreductive surgery has a very important role in the management of these patients because of the inherent chemoresistance and poor response to standard chemotherapy .

advanced mucinous ovarian cancer is a separate entity and has different biological behaviour . there is a wide range of therapeutic challenges and dilemmas in the management of these patients . the authors present a case of advanced ovarian mucinous cystadenocarcinoma with pseudomyxoma peritonei who had poor response to standard neoadjuvant chemotherapy . this case is highlighted to emphasize the challenges in the decision making for the management of advanced mucinous ovarian cancer .

in this study , 20 new bav isolates were obtained from mosquitoes collected from july through september during 2006 to 2007 at sites in gansu province ( latitude 3235n , 104107e ) , liaoning province ( 3941n , 123125e ) , shanxi province ( 3738n , 111113e ) , and inner mongolia province ( 4143n , 121123e ) ( table , figure 1 ) . mosquito samples were collected by using 12 v , 200 ma mosquito - trapping lamps ( wuhan lucky star environmental protection tech co. , ltd . , hubei , china ) and by collecting mosquitoes from 8:00 pm to 11:00 pm at nearby cow barns , a piggery , and fish pond sites where human activity was frequent . mosquitoes were put into a 20c freezer for 30 min and then were rapidly sorted into pools of 50 to 100 specimens according to species . location of new banna viruses ( bavs ) isolated in china ( red triangles ) and previously reported bav isolation sites ( black triangles ) . bav distribution sites in indonesia , vietnam , and part of china are located in tropical zones , which lie predominantly between the tropic of cancer and the equator . most bav distribution sites in china in the area from the tropic of cancer to latitude 45n belong to the northern temperate zone . 10296 - 028 ( invitrogen , carlsbad , ca , usa ) was used to extract total rna . cdna was prepared by using ready - to - go you - prime first - strand beads kit ( amersham pharmacia biotech , piscatawy , nj , usa ) according to the manufacturer s protocol . an 850-bp gene fragment from the 12th segment , which codes for the double - stranded rna binding protein , was amplified from the cdna of the bav isolates by using previously published primers ( 9 ) . pcr products were recovered by using purification kits ( qiagen , valencia , ca , usa ) , and then were inserted into pgem - t easy vector ( promega , madison , wi , usa ) . the insert sequence was determined by using m13 universal primers and an abi prism 3730 sequence analyzer ( abi , shirley , ny , usa ) . the genomic sequences of the 12th segment for the 20 new bav strains were determined ( genbank accession nos phylogenetic trees were constructed from the amplified region of the 12th segment sequence by using the molecular evolutionary genetics analysis ( mega ) version 4 software ( www.megasoftware.net ) from aligned nucleotide sequences . we used neighbor - joining algorithms with 1,000 replicates for bootstrap support of tree groupings . in this study , 38 bav strains isolated during 19872007 were analyzed , which included 30 strains isolated in china ( including 20 new bav isolates first reported in this study and 10 previously described isolates from china ( 8,1012 ) , 3 strains from indonesia , and 5 strains from vietnam ) ( table ) . initial bavs were isolated from indonesia and yunnan province of china , which belong to tropical and subtropical zones ( 2,5).the new bav isolates in our study were observed in gansu , shanxi , liaoning , and inner mongolia provinces of china ( northern china ) , which belong to the northern temperate zone . these strains represent a geographic distribution ranging from near the equator to latitude 45n , extending from the tropical zone to the northern temperate zone ( figure 1 ) . these data show that the distribution of bavs is not limited to southeast asia but that it extends into northeast asia as well . before our study , bav had been isolated from 7 mosquito species in 2 genera ( culex tritaeniorhynchus , cx . modestus , anopheles sinensis , and aedes vagus ) . to this list we now add 3 species in the genus aedes ( ae . phylogenetic analysis based on the complete coding sequence ( 624 nt ) of the 12th segment of the bav genome indicated that the bav isolates evaluated in this study could be divided into 2 phylogenetically different groups ( figure 2 ) . isolates from china and vietnam are included in group a , and the strains from indonesia are in group b. group a could be further divided into 2 subgroups , a1 and a2 . subgroup a1 includes 4 independent clades that group according to the location of collection and represent viruses from northern china ( gansu , shanxi , and liaoning provinces ) as well as the vietnam isolates . subgroup a2 includes isolates mainly from southern china ( yunnan province ) and vietnam , which is contiguous with yunnan province of china , as well as 2 isolates from northern china ( bj95 - 75/beijing , and nm0706/inner mongolia ) ( figure 1 ) . phylogenetic analysis based on the complete coding sequence of the 12th segment of banna viruses ( bavs ) currently isolated . phylogenetic analyses were performed by the neighbor - joining method using mega version 4 software ( www.megasoftware.net ) . the tree was rooted by using kadipiro virus and liaoning virus as the outgroup viruses . viruses were identified by using the nomenclature of virus strain / country / year of isolation / origin . our results demonstrate that bav strains are distributed from the tropics of southeast asia to the northern temperate regions of china . these observations suggest that the distribution of bav is wider than previously recognized and may be increasing . consistent with previous observations ( 9 ) , we report that bav isolates from china cluster in group a and separate into subgroups mainly according to the geographic origin of the isolate ; subgroup a1 is found in the north and subgroup a2 in the south . however , 2 isolates from northern china grouped in subgroup a2 ( south ) , and 3 isolates from vietnam grouped in subgroup a1 ( north ) . considering that group a isolates are geographically located across the monsoon climate zone , where south - to - north winds are common during summer ( 13 ) , bav could be transferred in infected mosquitoes during this period by the prevailing winds that move from southeast asia to east asia . in addition , bird migration , has been associated with the movement of other pathogens , and migration of infected birds through the east asia australasia flyway ( 13 ) , which traverses the region , may also account for this association . further study is required to determine if winds and birds are involved in dispersal of the virus . bav appears to be actively circulating in areas where japanese encephalitis virus ( jev ) is endemic ( 14 ) and where c. tritaeniorhynchus , which is the main vector of jev , is active . the clinical symptoms of disease caused by the 2 viruses is similar , and bav cases may be undetected during a je outbreak . it has been reported that 14% of clinically diagnosed je cases are bav immunoglobulin ( ig ) m positive ( 15 ) , indicating that bav epidemics may have occurred but have been clinically misdiagnosed as japanese encephalitis . the apparent active transmission of bav over a large geographic area , genetic variation between geographic regions , and the potential to cause severe disease underscore the need for additional surveillance , further characterization , and improved diagnostic systems worldwide .

banna viruses ( bavs ) have been isolated from pigs , cattle , ticks , mosquitoes , and human encephalitis patients . we isolated and analyzed 20 bavs newly isolated in china ; this finding extends the distribution of bavs from tropical zone to north temperate climates and demonstrate regional variations in bav phylogeny and mosquito species possibly involved in bav transmission .

during disease monitoring , a stem with small , irregular , brown lesions was sampled at a farm in cheonan , chungnam province , in september of 2011 . the infected twig was rotted , and sunken cankers and reddish - brown needles were seen on the infected twig ( fig . 1 ) . after incubation in a humid condition , white mycelia , having dark brown necrosis , developed around the twig cavity . prior to further analysis the ducc505 isolate was grown on pda and maintained at 25. a 5-mm diameter mycelial plug was cut from the margin of a 5-day - old culture of the isolate , and was placed centrally in an 85-mm petri dish containing pda . the isolate was cultured at 25 , and colony characteristics such as color , shape and size were recorded . the colony diameter was measured daily by scoring the average length for a period of 7 days . colonies were whitish , having crenated edges , aerial mycelium on the surface , and with black gregarious fruiting bodies ( fig . conidia were 17~22 3.5~4.2 m , fusiform , 4-septate , and straight to slightly curved . the basal cell was of conical shape with an obtuse end , and pale brown in color . the three median cells were brown : the second cell from base was pale brown , the third cell was a darker brown , and the fourth cell was brown . there were 2~3 tubular , apical appendages arising from the apex of the apical cell . the ducc505 isolate grew better on pda than oat meal agar and malt extract agar ( fig . the optimum temperature for mycelial growth of the isolate ducc505 on pda was 25 ( fig . the isolate ducc505 grew well in a broad range of ph , from 5 to 10 ( fig . 3c ) . these growth properties could be attributed to overcome the ph and low temperature stress in environment . so far , none of fungicides have been registered for the disease control of acanthopanax sp . in the agrochemical use guide book in korea . also , no fungicide has ever been tested for p. ellipsospora isolated from acanthopanax sp . we therefore tested five kinds of fungicides for this study that are commercially available for ascomycete plant pathogens in korea . to understand the agrochemical sensitivity of the ducc505 isolate , we grew it with different concentration of fungicides , and the results are summarized in fig . 3d . in the benomyl and tebuconazol supplemented media , the mycelial growth was completely inhibited at 10 g / ml . this result is similar to pestalotiopsis microspora that is sensitive to tebuconazole . however , the isolate showed relative resistance in all media containing azoxystrobin , dimethomorph and triflumizole . overall , it is suggested that among the five fungicides , benomyl and tebuconazol are the appropriate choice for the control of p. ellipsospora . the ducc505 fungal isolate was grown on pda plates for 5 days at 25. mycelia were harvested by scraping the fungal colonies with a sterile blade . genomic dna was extracted as described by kim et al . , with modifications . from the extracted genomic dna , partial translation elongation factor 1 polymerase chain reaction ( pcr ) was performed as described previously using the universal primers tef728 ( 5'-cat cga gaa gtt cga gaa gg-3 ' ) and tef1 ( 5'-gcc atc ctt gga gat acc agc-3 ' ) . the pcr products were purified with a high pure pcr purification kit ( roche , basel , swiss ) and sequencing was carried out by macrogen inc . the nucleotide sequence of partial tef1- gene of the fungal isolate shares 99% ( 531/536 ) sequence identity with that of known pestalotiopsis ellipsospora . the tef1- gene sequence of the ducc505 was deposited in genbank dna database under accession number kc534872 . 4 ) . thus , based on the molecular and morphological data generated , the isolate was identified as p. ellipsospora . the young twigs were inoculated with a droplet of the ducc505 conidia suspension ( 1.3 10 conidia / ml ) , which was prepared from the fungal cultures grown on pda . the inoculated young twigs were incubated in a humid chamber at 25 for 7 days . as rotting progressed , superficial white mycelium and small black acervuli were observed ( fig . 5 ) . p. ellipsospora was reisolated from the rotted twig lesion , thus fulfilling koch 's postulates . these results demonstrated that p. ellipsospora ducc505 was able to infect a twig of a. divaricatus . this is the first detailed report describing p. ellipsospora isolated from acanthopanax in korea , and it appears to be the first confirmation proving its pathogenicity on acanthopanax twigs .

acanthopanax divaricatus , a member of the araliaceae family , has been used as an invigorant in traditional korean medicine . during disease monitoring , a stem with small , irregular , brown lesions was sampled at a farm in cheonan in 2011 . the symptoms seen were sunken cankers and reddish - brown needles on the infected twig . the isolated fungal colonies were whitish , having crenated edges and aerial mycelium on the surface , and with black gregarious fruiting bodies . the reverse plate was creamy white . conidia were 17~22 3.5~4.2 m , fusiform , 4-septate , and straight to slightly curved . the nucleotide sequence of the partial translation elongation factor 1 alpha gene of the fungal isolate , shares 99% sequence identity with that of known pestalotiopsis ellipsospora . based on the results of the morphological and molecular analyses , the fungal isolate was identified as p. ellipsospora . in korea , this is the first report of canker on a. divaricatus .

align and center the narrow end of the large reducer base on the camera hole of the smartphone cover . the area of contact of the reducer and cover is then carefully glued [ fig . 2 ] . the 50 mm pipe is used as the optical tube . a piece of sandpaper 17 cm 14.8 cm , is rolled and inserted into the tube and glued , the sanded surface facing inward to prevent dazzle . another 15.5 cm 2 cm sandpaper is glued inside the reducer base leaving 1.0 cm bare area toward the wider end [ fig . the reducer glued to the back cover sandpapers used to reduce the dazzle insulation tape is used to camouflage the optical tube and reducer base . at one end , for the condensing lens , apply 812 rounds of tape for snug fitting of the lens [ fig . the phone is positioned in the cover , the optical tube inserted into the reducer , the 20 d fixed and the handheld device is ready [ fig . the centers of the camera and flash are separated beyond 1 cm , a longer optical tube will be required . ( a ) the optical tube camouflaged with insulation tape . to fit the 20 d , on each cardboard , make a hole to fit the bolt ( 8 mm for haag - strait model / carl zeiss slit lamps or 6 mm for topcon model slit lamps ) , using a pointed knife / mica cutter and scissors , centered at 2.5 cm from one of its edges . the nut is tightened on the bolt , and the bolt passed through the holes in the cardboard pieces and tightened . the washer glued , centering the inner ring on the bolt at the under surface of the cardboards . the small reducer is glued on the platform with its wider side facing up at the opposite edge [ fig . a 40 mm pipe , 10 cm long , is fixed to the reducer [ fig . a 50 mm pipe is cut transversely , at approximately two - third of its diameter , to a length of 10 cm , and the smaller piece is discarded . the larger piece is then glued with its concave surface facing up , to the second small reducer , on to its narrower end as in fig . alternatively , using spray painting can enhance the appearance ( optional ) [ video 1 ] . to use the diyretcam on the slit lamp , move the observation illumination columns to one side , and fix the mount by placing the bolt in the slot for the focusing rod [ fig . for slit lamps with larger diameter slots , a few rounds of insulation tape on the bolt will improve stability . the diyretcam can now be used like a fundus camera using the joystick [ fig . 5 g ] , with the camera in the continuous flash on mode . as in indirect ophthalmoscopy , the images are laterally reversed and vertically inverted , and therefore the movements to align the field of view , will be in opposite direction to the images seen . in the handheld method , one can hold the optical tube or the camera or the 20 d lens [ fig . 6a and b ] , and use the camera in the photo or video mode . in video mode , imaging of the peripheral retina till pars plana [ fig . ( a ) the do it yourself smartphone fundus camera used as a hand held the device . ( b ) the do it yourself smartphone fundus camera can be held at the condensing lens and supported with the other hand on the camera . ( c ) like in indirect ophthalmoscopy , scleral depression is done after stabilizing the do it yourself smartphone fundus camera stereo pair showing pars plana cysts the camera app which is preloaded in the smartphone is good enough for basic fundus photography . we have used camera fv-5 and cinema fv-5 ( fgae studios , germany , http://www.cinemafv5.com/index.php ) for android and camera plus ( global delight technologies , udupi , india , www.globaldelight.com/iphone/cameraplus ) for iphone and these apps give more control on the image capture with various options such as focus lock and exposure lock . image editing can be done on the smartphone itself using adobe photoshop express ( adobe systems incorporated , www.photoshop.com/products/photoshopexpress ) . editing involves capturing the screenshot of the desired frame from the video and opening the screenshot or image in photoshop [ fig . 8a ] . the image is then cropped , rotated to proper orientation [ fig . , ( d ) the blemish removal tool is used to remove the reflections ( e ) after removing the reflections . ( f ) the circle black mask is applied diyretcam captures cost - effective [ table 2 ] quality fundus images . stereo fundus photography of the central [ fig . 9 ] and peripheral retina [ fig . 7 ] are possible with the diyretcam . the diyretcam is a cost - effective option for documenting the fundus changes in retinopathy of prematurity [ fig . although useful in such settings , this device is not intended to replace the fundus camera especially in macular imaging , where , the fundus camera with its reflex free , high - quality imaging gives a better resolution of the macular details . stereo pair taken with the do it yourself smartphone fundus camera shows a recurrent retinal detachment with macular hole . note the bullous detachment inferonasally stereo pair of a zone ii stage 3 retinopathy of prematurity showing popcorn lesions . the mount of the scleral depressor is clearly made out in stereo holding the phone with one hand and the 20 d lens with the other hand helps to stabilize the device during the learning curve . once familiar with this technique , the device can be held with the hand holding the 20 d lens , with the optical tube resting within the web of the thumb and the index finger . we made this device with commonly available materials on the do - it - yourself , the mount can be made from sturdier materials like medium density fibreboard ( mdf ) or polyvinyl chloride ( pvc ) pipes , with custom made anchoring bolt , giving a better appearance , and stability to the device . this device is also capable of capturing good quality anterior segment photographs as well [ fig . ( a ) preinjection photo with only the barrier filter , showing dense asteroid hyalosis . ( b ) the mid - phase fundus fluorescein angiography showing capillary nonperfusion , macular ischemia and neovascularization on the disc suggestive of neovascular branch retinal vein occlusion with macular ischemia anterior segment photographs taken with the do it yourself smartphone fundus camera . ( a ) vascular pterygium ( b ) wrinkling of the posterior capsule in a pseudophakic eye there are no conflicts of interest .

this article describes the method to make a do it yourself smartphone - based fundus camera which can image the central retina as well as the peripheral retina up to the pars plana . it is a cost - effective alternative to the fundus camera .

type i neurofibromatosis , also referred to as von recklinghausen s disease , is an autosomal dominant disease characterized by neurofibromas and abnormal cutaneous pigmentation ( cafe - au - lait spot ) . its malignant transformation , that is malignant peripheral nerve sheath tumor ( mpnst ) , accounts for about 510 percent of all soft tissue tumors . common site of the origin for mpnst is the lower and upper extremities , trunk , head and neck . we have recently experienced a case of intrathoracic mpnst in a patient with von recklinghausen s disease . a 40-year - old man presented to chonbuk national university hospital , chonju , korea , due to one rapidly enlarging palpable mass in the right neck which was extended to the supraclavicular fossa . physical examination showed a firm , non - tender and fixed mass associated with ptosis of right eyelid , engorgement of right neck vein , facial swelling and multiple cafe - au - lait spots and pigmented nodular skin lesions on the chest wall and both arms ( figure 1 . chest radiography showed an increased homogeneous mass density at right upper lung field with well - demarcated margin and elevation of right side diaphragm ( figure 1 . magnetic resonance imaging ( mri ) scan of the thorax revealed a homogeneous , well - enhanced and well - circumscribed mass measuring 12108 cm . the central portion of the huge mass showed necrotic tissue which was high signal intensity in t-2 weighted image and low signal intensity in t-1 weighted image . the main mass was located in right upper hemithorax and was associated with multiple adjacent lymphadenopathy . the lesion compressed the trachea , esophagus , right carotid and subclavian artery , and encased the brachial plexus ( figure 1 . , it showed nodular growth pattern and conspicious necrosis in the tumor . densely cellular fascicles alternated with hypocellular zones where the parallel orientation of the cell was lacking ( figure 1 . the nuclei were wavy , buckled , irregular - shaped or occasionally comma - shaped , and the cytoplasm was lightly stained and usually indistinct ( figure 1 . immunohistochemical stain for s-100 protein showed positive reaction on the cytoplasm of tumor cells ( figure 1.(f ) ) . von recklinghausen s disease ( neurofibromatosis type i ) is an autosomal dominant disease with an incidence of about 1 in 3,000 live births . the clinical features of this disorder invariably include cafe - au - lait spots , multiple neurofibromas , lisch nodules or pigmented iris hamartomas . the schwann cell most likely is the cell of origin , but some may originate from perineurium or endoneurium . in our case , the patient showed multiple cafe - au - lait spots and pigmented nodular skin lesions over the chest wall and both arms . mpnst is a kind of malignant tranformation of type i neurofibromatosis , with an incidence recently reported at about 510% . malignant transformation usually occurs in a neurofibroma , which has been present for an extended period of time . the most common anatomic location for malignant schwanomas is the lower and upper extremities , trunk , head and neck , and miscellaneous sites in descending order . this presented case showed an increased homogeneous mass density at the right upper lung field , with well - demarcated margin and elevation of right hemidiaphragm on chest radiographies . radiologic study revealed a homogeneous , well - enhanced and well - circumscribed mass measuring 12108 cm . in our case , the mass was located in the thoracic cavity , extending toward the right supraclavicular fossa and associated with multiple adjacent lymphadenopathy . this lesion compressed the trachea , esophagus , right carotid and subclavian artery , and encased the brachial plexus that caused neurologic manifestation , such as radiating pain with mild numbness , motor weakness of right upper extremity and ptosis . in our case , the histologic examinations of the nodular skin lesion showed expansion of endoneurium by myxoid ground substance , such as neurofibroma . the histologic examinations of intrathoracic mass showed consistent with malignant peripheral nerve sheath tumor which was stained with s-100 protein . our case was not accessible to operate due to the extension of the tumor to adjacent mediastinal structure , so we started radiofrequency ablation and doxorubicin - based chemotherapy . we report a case of intrathoracic mpnst in a 40-year - old man with neurofibromatosis . review of the literature showed that intrathoracic mpnst is very rare but shows highly aggressive manifestation of malignancy and poor prognosis . so , intrathoracic mpnst should be considered in the differential diagnosis of intrathoracic mass in young men with von reckling - hausen s disease .

malignant peripheral nerve sheath tumor ( mpnst ) is defined as any malignant tumor arising from or differentiating toward the cells of the peripheral nerve sheath . mpnst accounts for about 510% of all soft tissue tumors and is often associated with neurofibromatosis type i ( nf-1 , von recklinghausen s disease ) . it is one of the malignant tumors associated with von recklinghausen s disease . its common site is the lower and upper extremities , trunk , head and neck . but intrathoracic manifestations are very rare . we report a case of a 40 year - old man with multiple neurofibromatosis who was presented with an intrathoracic malignant peripheral nerve sheath tumor .

medline via ovid , embase , and cochrane library were searched using the keywords : ( total disk replacement , prosthesis , implantation , discectomy , and arthroplasty ) and ( cervical vertebrae , cervical spine , and spine ) and ( systematic reviews , reviews , and meta - analysis ) . the initial search was conducted on 18 august 2013 and updated on 02 february 2015 . eligibility criteria , which were applied by two reviewers independently ( oat , ka ) , were : the article should be a systematic review and/or meta - analysis of randomised controlled trials ( rcts ) or cohort studies that compared c - adr with acdf at the cervical region for one or two levels and for follow - up period of at least more than 6 months and should be published in a peer - reviewed journal . no time or language limits were applied in the selection process . two reviewers ( oat , he ) then assessed the quality of the selected reviews and meta - analyses using the 11-item amstar score which is a validated measurement tool to assess the methodological quality of systematic reviews ( 2 ) . the 11 items are summarised as follows : the research question and inclusion criteria should be established before the conduct of the review.at least two reviewers should extract the data independently and a consensus procedure to resolve their disagreement should be in place.at least two electronic sources should be searched.the authors should state that they searched for reports regardless of their publication type.a list of included and excluded studies should be provided.the characteristics of the included studies should be provided.the scientific quality of the included studies should be assessed and documented.the scientific quality of the included studies should be used appropriately in formulating conclusions.the methods used to combine the findings of studies should be appropriate ( need to assess homogeneity).the likelihood of publication bias should be assessed.the conflict of interest should be declared and included . the research question and inclusion criteria should be established before the conduct of the review . at least two reviewers should extract the data independently and a consensus procedure to resolve their disagreement should be in place . the methods used to combine the findings of studies should be appropriate ( need to assess homogeneity ) . the likelihood of publication bias should be assessed . the two assessors had to decide whether the systematic review or the meta - analysis meets the criterion ( score 1 ) or can not decide on an item or that the review does not meet the criterion ( score 0 ) . screening of full reports of 46 relevant abstracts resulted in the selection of 15 eligible systematic reviews and/or meta - analyses . the two reviewers inter - rater agreement level was high , as indicated by kappa of > 0.72 ( 3 ) . in other words , the two assessors reached perfect agreement in 12 out of the 15 systematic reviews assessed . the amstar score of the reviews ranged from 3 to 11 ( see table 1 ) . five studies scored below 5 ( amstar ) indicating that these reviews are either of low quality or failed to report their methodology in selecting and critically appraising the studies included . the most significant drawbacks of reviews of a score below 5 were : not using an extensive search strategy , failure to use the scientific quality of the included studies appropriately in formulating a conclusion , not assessing publication bias , and not reporting the excluded studies . the amstar items that were consistently missing were : 5 ( 86.7% of the reviews did not report excluded studies ) , 8 ( 66.7% of the reviews failed to account for the quality of articles when formulating conclusions ) , 10 ( 80% of the reviews did not attempt to measure publication bias ) , and 11 ( 80% of authors failed to disclose or report any conflict of interest ) . quality assessment of included systematic reviews percent of overall agreement of the two assessors was : 0.799999 . with the significant exception of cochrane reviews , the methodological quality of systematic reviews evaluating the evidence of c - adr versus acdf has to be improved specifically in transparent reporting . it is clear that conflict of interest disclosure might have been disclosed to journal editors but failure to report this in the review will lead to lower score in amstar and the readers might question the bias of authors . more significantly , reporting of excluded studies , with reasons of exclusion , in systematic reviews is an essential part of the reviewing process , and authors of systematic reviews and meta - analyses should be encouraged to report this as this assures the readers and the users of the results of the systematic reviews that the article selection process is robust and unbiased . there are , of course , some challenges in the rcts of surgically interventions including the limitation to select a random sample of patients , the impracticality of blinding surgical interventions . nevertheless , systematic reviews have to apply rigorous methodology to inform clinicians , patients , and guidelines decision bodies . it is essential to follow the guidelines of cochrane collaboration , or an equivalent organisation such as the centre for reviews and dissemination at york , when conducting systematic reviews or meta - analyses . there are many resources available for training and consulting whenever a research team plans to do a systematic review . it must be acknowledged that the systematic review is similar to any other scientific articles and can be of varying quality . systematic reviewing is team work and a team of three or more is usually required with at least one statistician included in the team . the team has to have an expertise in the topic reviewed and has to carry the systematic review according to a pre - planned protocol . the work usually takes 912 months to complete depending on the number of articles retrieved . the centre for reviews and dissemination at york summarise the steps to conduct a systematic review as follows : clear stated objectives.pre-defined eligibility criteria for studies.a systematic search of literature with at least two databases searched.assessment of validity of findings ( e.g. risk of bias).systematic presentation and synthesis of evidence . we also recommend the use of prisma chick list ( www.prisma-statement.org/2.1.2 - prisma 2009 checklist.pdf ) and amstar assessment tool ( www.amstar.ca/amstar_checklist.php ) when conducting systematic reviews . all authors contributed to the writing of the first draft and all approved the last draft . the two sponsors had no role in the study , decision to publish , or any copyright relevant to the study .

cervical artificial disc replacement ( c - adr ) is now an alternative to anterior cervical discectomy and fusion ( acdf ) . many studies have evaluated the efficacy of c - adr compared with acdf . this led to a series of systematic reviews and meta - analyses to evaluate the evidence of the superiority of one intervention against the other . the aim of the study presented here was to evaluate the quality of these reviews and meta - analyses . medline via ovid , embase , and cochrane library were searched using the keywords : ( total disk replacement , prosthesis , implantation , discectomy , and arthroplasty ) and ( cervical vertebrae , cervical spine , and spine ) and ( systematic reviews , reviews , and meta - analysis ) . screening and data extraction were conducted by two reviewers independently . two reviewers then assessed the quality of the selected reviews and meta - analysis using 11-item amstar score which is a validated measurement tool to assess the methodological quality of systematic reviews . screening of full reports of 46 relevant abstracts resulted in the selection of 15 systematic reviews and/or meta - analyses as eligible for this study . the two reviewers inter - rater agreement level was high as indicated by kappa of > 0.72 . the amstar score of the reviews ranged from 3 to 11 . only one study ( a cochrane review ) scored 100% ( amstar 11 ) . five studies scored below ( amstar 5 ) indicating low - quality reviews . the most significant drawbacks of reviews of a score below 5 were not using an extensive search strategy , failure to use the scientific quality of the included studies appropriately in formulating a conclusion , not assessing publication bias , and not reporting the excluded studies . with a significant exception of a cochrane review , the methodological quality of systematic reviews evaluating the evidence of c - adr versus acdf has to be improved .

a 60-year - old man presented to the emergency room with a sudden onset of intractable pain in the left leg . the patient had a history of intermittent abdominal pain and hypertension without other risk factors for atherosclerosis . a computed tomographic angiogram ( cta ) revealed chronic total occlusion of the abdominal aorta from the inferior mesenteric artery level to the level of both common iliac arteries ( fig . the cta also showed chronic total occlusion of the left external iliac artery and acute total occlusion of the left popliteal artery ( fig . , the popliteal artery occlusion was removed , and angiography confirmed good distal run - off through the anterior and posterior tibial arteries ( fig . however , 3 days after the procedure , the patient suffered from the same intractable pain in the left leg . repeated femoral angiography showed a recurrence of the acute total occlusion of the left popliteal artery . after repeated endovascular treatment , urgent surgery was performed to prevent the reoccurrence of thromboembolism . exploration of the abdominal aorta found fresh white clots that were adherent to the aortic wall ( fig . resection of the abdominal aorta below the inferior mesenteric artery was followed by aortic replacement with a 201010-mm dacron y graft ( meadox medicals , oakland , nj , usa ) . distal anastomosis of the right and left arteries was performed on the common iliac artery and common femoral artery levels , respectively ( fig . however , due to the abnormal ranges of the platelet count since the first day of admission ( ranging from 53310/l to 1,14910/l ) , a bone marrow biopsy was performed postoperatively . the exam showed markedly increased numbers of megakaryocytes , which were clustered with mature cytoplasm and hyper - lobulated nuclei . therefore , the final diagnosis of the patient was essential thrombocytosis ( et ) , according to the 2008 world health organization ( who ) diagnostic criteria . medical therapy was started immediately with hydroxyurea and aspirin once daily at doses of 1,000 mg and 100 mg , respectively . the platelet count decreased gradually and the patient was discharged on postoperative day 17 without any complications . the therapeutic target for the platelet count ( < 40010/l ) was achieved 2 months after surgery . on the last follow - up , more than 2 years after the operation , the patient was in good condition with a patent graft ( fig . et is an uncommon myeloproliferative disorder in which a proliferation of megakaryocytes in the bone marrow leads to an elevated platelet count . et is defined by the following 4 major criteria : ( 1 ) platelet count 45010/l ; ( 2 ) megakaryocyte proliferation with large and mature morphology , and little to no granulocyte or erythroid proliferation ; ( 3 ) not meeting the 2008 who criteria for chronic myelogenous leukemia , polycythemia vera , primary myelofibrosis , myelodysplastic syndromes , or any other myeloid neoplasm ; and ( 4 ) demonstration of jak2 or other clonal markers , or no evidence of reactive thrombosis . in general , common causes of aortic thrombosis include cardiac sources of embolism , hypercoagulable states , and other complications from atherosclerotic disease . although et remains an uncommon cause of aortic pathology , some reports have discussed cases of et - associated aortic mural thrombus . to the best of our knowledge , et caused a chronic obstruction of the abdominal aorta and acute obstruction of the arteries . we encountered a fast recurrence of artery occlusion ( 3 days after thrombus removal ) . we would have been able to prevent the recurrence of popliteal artery occlusion if we had immediately controlled the platelet count . many options exist for managing et , such as medical therapy with heparin anticoagulation , aspirin , and cytoreductive chemotherapy , and surgical treatment with aortic thrombectomy and/or endovascular surgery . in order to ensure the optimal treatment of et , the location of the thrombus , potential for embolism , individual risk of the patient , and the pathology of the thrombus we decided to perform surgical treatment due to the rapid formation of the thrombus , the location of the original chronic thrombus , and the insufficiency of endovascular treatment . according to harrison et al . , hydroxyurea and low - dose aspirin are superior to other combinations of drugs for patients with et at high risk for vascular events , especially arterial thrombosis . in our case , once the diagnosis of et was made , the patient was treated with hydroxyurea and low - dose aspirin for a goal platelet count of < 40010/l . the patient s platelet count was normalized and maintained within a range of 21910/l to 25210/l . in conclusion , although et rarely presents in large vessels , early diagnosis and immediate management are essential .

essential thrombocytosis ( et ) is a myeloproliferative disorder characterized by an anomalous increase in platelet production . many patients with et are asymptomatic . few studies have reported et - associated thromboembolism in large vessels such as the aorta . we report a patient with et who presented with peripheral embolism from an abdominal aortic thrombus and developed acute limb ischemia . the patient underwent aortic replacement successfully . the patient s platelet count was controlled with hydroxyurea , and no recurrence was noted over 2 years of follow - up .

diagnostic tests for tbe in israel have been available since 2006 and are performed only in the israeli central virology reference laboratories ( tel hashomer , israel ) of the israeli ministry of health by using an indirect immunofluorescence commercial kit ( euroimmun ag , lbeck , germany ) according to manufacturer instructions . as numerator , we included all confirmed cases of tbe ( according to criteria adopted by the european commission in 2012 ) . during 20062014 , a total of 4 tbe cases were diagnosed in israel : 1 case each acquired in austria , russia , and sweden and 1 case acquired in either germany or in switzerland ( table 1 ; technical appendix ) . as denominator we used 2 sets of data . for the first , in emulation of steffen et al . ( 5 ) , we calculated tbe attack rate per 100,000 traveler entries during the study period , according to the number of israeli tourists obtained from the united nations world tourism organization database ( table 2 ) . the combined attack rate for these countries ( according to whether germany or switzerland was considered the place of acquisition of 1 case ) ranged from 1 case per 837,528 to 1 case per 573,493 israeli tourist entries . because the united nations world tourism organization database lacks information about duration of stay , we also used data on the absolute number of nights stayed by israeli travelers during the study period from the published tourism statistics of switzerland , germany , and austria ( 1012 ) ( similar data for russia were lacking ) ; for sweden , we obtained the number of overnight stays from statistics sweden ( e. meltzer , unpub . tbe incidence ranged from 1 case per 697,700 person - weeks ( germany ) to 1 case per 16,270 person - weeks ( sweden ) , which is equivalent to an annual incidence of 7.5321.0 cases/100,000 travelers per year of travel ( table 2 ) . tbe is endemic to some of the most popular tourist destinations in developed countries , raising questions about vaccination and advice to travelers . however , there is such a dearth of published research on the actual risk to travelers that tbe is termed a neglected disease in travel medicine ( 13 ) . a 2016 study of travel - related tbe estimated an attack rate of 1 case per 1.32 10 tourist - entries , concluding that vaccination should be offered only to travelers planning activities resulting in at - risk exposures ( 5 ) . by using travel duration data , we found that the actual tbe incidence rate in travelers from israel to sweden , austria , germany , and switzerland ( table 2 ) is at least as high as that of the local population ( 5/100,000 in austria and < 1/100,000 in germany , for example ) and is higher than the who - recommended threshold for universal tbe vaccination ( an annual incidence > 5/100,000 population ) ( 14 ) . these studies also suggest a substantial tbe risk to travelers that is similar in range to our results ( table 2 ) . when event numbers are small runs the risk for overestimation , according to the law of small numbers . however , by considering the total period of tbe test availability in israel ( 9 years ) , rather than just the years in which cases were detected , we believe we avoided such overestimation . in addition , reporting of notifiable diseases might be incomplete , and clinicians awareness of the need to consider tbe in a returning traveler from europe or northern asia probably is insufficient . also , milder tbe cases might have been overlooked . statistics on overnight stays might not include some travelers , such as expatriates in private residences or those staying with families . on the other hand , in such travel scenarios we believe the combined effect of these limitations is more likely to have led to an underestimation than an overestimation of tbe risk for travelers . indeed , our calculations included all israeli tourists traveling in all seasons , whereas as shown in the 4 cases reported here as well ( table 1 ) , tbe risk is seasonal : were only summer tourists considered , incidence rates of travel - related tbe probably would have been even higher . it is interesting to compare the data presented here on tbe to another travel - related , vaccine - preventable flavivirus : japanese encephalitis ( je ) . the risk for je among travelers is considered low : < 1/1 10 travelers staying 1 month ( which equals an incidence lower than 1.2 cases/100,000 travelers / year of travel ) ( 2 ) . our findings , as well as those of previous reports , suggest that the risk posed by tbe far exceeds that posed by je to travelers . only 1 case of je in an israeli traveler has been reported in > 2 decades ( 15 ) , whereas at least 4 tbe cases were diagnosed during the past 9 years . similar to je , tbe had been documented to cause severe and fatal illness among travelers , but whereas je vaccines for travelers are promoted by most government advisory boards in developed countries , very little is done regarding tbe vaccination . this difference probably underlies the fact that in israel , for example , during 20122014 , a total of 46,773 je vaccine doses were distributed , whereas only 960 tbe vaccine doses were sold during the same period ( e. schwartz , unpub . data ) . in conclusion , actual incidence of tbe among israeli travelers to austria , germany , sweden , and switzerland appears to be higher than the threshold recommended by who for universal tbe vaccination . vaccination should be recommended to all travelers with potential exposure to tick habitat in these destinations .

during 20062014 , four tick - borne encephalitis ( tbe ) cases occurred among israeli travelers . we calculated tbe incidence at 321.0 , 45.0 , 13.2 , and 7.5 cases/100,000 travelers / year of travel to sweden , switzerland , austria , and germany , respectively . tbe incidence among travelers to these destinations appears to justify tbe vaccination in accordance with world health organization recommendations .

the previous issue of critical care includes a report of a multicenter study in which cardiac index and gastric mucosal ph targets were compared during resuscitation of patients with septic shock . similar to all other hemodynamic variables with the exception of central venous oxygen saturation , the value of a cardiac index target in the resuscitation of patients in septic shock has not been established . in contrast , achievement of other goals in the treatment of septic patients ( for instance , early and adequate antibiotic treatment ) has been associated with improved outcomes . because ' normal ' systemic hemodynamics do not necessarily guarantee adequate tissue oxygen supply , monitoring organ perfusion or function it has been shown that persistent microcirculatory alterations are associated with organ failure and mortality in patients with septic shock . gastric mucosal ph ( phi ) is an interesting parameter that has been shown to predict outcome in many patient groups . phi is a composite variable that reflects not just adequacy of local perfusion but also systemic metabolic acid - base homeostasis and ventilation . the interaction of the components of phi and their response to treatment may confound the interpretation and prognostic relevance of gastric mucosal acidosis . in the study conducted by palizas and coworkers , resuscitation to a phi goal conceptually , there are four interpretations of these findings : the tested variables ( cardiac index and phi ) are not relevant to survival ; the defined targets were not adequate ; the targets were relevant but only in combination with the achievement of other goals ; and finally , the efforts to achieve the goals were not adequate , and the goal therefore was not achieved . cardiac output determines tissue oxygen delivery and is certainly an important variable with respect to the resolution of septic shock . however , other variables contribute to tissue oxygen transport , and the demands may also vary . in that sense , as the authors state themselves , a goal representing a presumed adequate relationship between oxygen delivery and consumption ( for example , mixed venous oxygen saturation ) would have been preferable . its strong association with mortality makes phi an ideal target variable for improving outcomes . in the study reported by palizas and coworkers , the target cardiac index was achieved at baseline in nearly 90% of patients . because the mortality was 30% , it is clear that the target should have been higher , if increasing cardiac index is believed to be beneficial . it is a relatively common practice to increase minute ventilation in order to normalize arterial ph when bicarbonate is low . whether a ( normal ) phi of 7.32 can be achieved at all during the early phase of septic shock is questionable . the use of vasoconstrictors can decrease mesenteric perfusion , and metabolic effects of adrenaline ( epinephrine ) may increase pco2 further . there is no information on how other aspects of septic shock treatment were addressed ( antibiotics , source control , ventilator settings , and so on ) the authors indicate that crystalloids and colloids were given , but in their protocol only saline is listed . although colloids can be harmful in sepsis , normal saline ( or colloids in saline ) can cause hyperchloremic metabolic acidosis and thereby decrease mucosal phi . adrenaline ( epinephrine ) , noradrena - line ( norepinephrine ) , dopamine , and dobutamine were used to improve blood pressure and flow . although adrenaline can impair splanchnic perfusion in septic shock , dobutamine appears to be able to reverse these changes , at least in part . phi was measured every 6 hours , and no data are given on the frequency of cardiac index assessments . four daily assessments of the treatment 's influence on the target variable may be too few , especially in view of the fact that splanchnic blood flow is highly variable in septic patients . it would have been interesting to see how the individual therapeutic interventions influenced the target variables . without this information , nevertheless , the work by palizas and coworkers reminds us that mucosal acidosis persists in the majority of patients who ultimately will die after resuscitation from septic shock . monitoring and treating cardiac output determines tissue oxygen delivery and is certainly an important variable with respect to the resolution of septic shock . however , other variables contribute to tissue oxygen transport , and the demands may also vary . in that sense , as the authors state themselves , a goal representing a presumed adequate relationship between oxygen delivery and consumption ( for example , mixed venous oxygen saturation ) would have been preferable . in the study reported by palizas and coworkers , the target cardiac index was achieved at baseline in nearly 90% of patients . because the mortality was 30% , it is clear that the target should have been higher , if increasing cardiac index is believed to be beneficial . in contrast , the incidence of low phi was high . however , the variable is influenced by arterial carbon dioxide tension ( pco2 ) . it is a relatively common practice to increase minute ventilation in order to normalize arterial ph when bicarbonate is low . thus , the mucosalarterial pco2 gradient would have been a better choice . whether a ( normal ) phi of 7.32 can be achieved at all during the use of vasoconstrictors can decrease mesenteric perfusion , and metabolic effects of adrenaline ( epinephrine ) may increase pco2 further . there is no information on how other aspects of septic shock treatment were addressed ( antibiotics , source control , ventilator settings , and so on ) the authors indicate that crystalloids and colloids were given , but in their protocol only saline is listed . although colloids can be harmful in sepsis , normal saline ( or colloids in saline ) can cause hyperchloremic metabolic acidosis and thereby decrease mucosal phi . adrenaline ( epinephrine ) , noradrena - line ( norepinephrine ) , dopamine , and dobutamine were used to improve blood pressure and flow . although adrenaline can impair splanchnic perfusion in septic shock , dobutamine appears to be able to reverse these changes , at least in part . phi was measured every 6 hours , and no data are given on the frequency of cardiac index assessments . four daily assessments of the treatment 's influence on the target variable may be too few , especially in view of the fact that splanchnic blood flow is highly variable in septic patients . it would have been interesting to see how the individual therapeutic interventions influenced the target variables . without this information , nevertheless , the work by palizas and coworkers reminds us that mucosal acidosis persists in the majority of patients who ultimately will die after resuscitation from septic shock . monitoring and treating the department of intensive care medicine at inselspital has or has had research contracts and/or collaboration contracts with edwards lifescience , ge healthcare , pulsion , orion pharma , berna biotech and b. braun medical .

the need to achieve adequate tissue oxygen delivery early in patients with septic shock is well established . however , it is less well recognized that tissue hypoperfusion can exist despite normalization of systemic hemodynamics . efforts to resuscitate septic patients until adequate tissue perfusion has been achieved can potentially improve outcome . in a multicenter study , 130 patients with septic shock were resuscitated within 12 hours of diagnosis using a protocol including goals for mean arterial and pulmonary artery occluded pressures , urinary output , arterial ph , and hemoglobin goals . they were then randomly assigned to further resuscitation with either a cardiac index ( 3 l / minute per m2 ) or a gastric mucosal ph ( 7.32 ) target . the intensive care unit length of stay and 28-day mortality did not differ between groups , but more patients in the cardiac index group were in the target range , both at baseline and after resuscitation , as compared with the gastric mucosal ph group . in contrast to cardiac index , gastric mucosal ph at baseline and at 24 and 48 hours predicted mortality . whether other targets for the chosen variables , or different and in particular earlier resuscitation efforts would have favored one group can not be concluded from the data provided .

ossifying fibromas are the well - defined type of a benign fibro - osseous lesion of jaws . the jof is a controversial lesion that has been distinguished from the larger group of ossifying fibroma on the basis of the age of the patients , the most common sites of involvement , and clinical behavior . it is considered a separate entity from ossifying fibroma due to its locally aggressive behavior and propensity to occur at an adolescent age . the most distinguishing feature of ossifying fibroma is the well - circumscribed appearance of the lesion radiographically , clinically , and the ease with which it is separated from the normal bone surgically . microscopically , it has a characteristic feature of irregularly mineralized cellular osteoid strands lined by plump osteoblasts . most jofs arise in the vicinity of the paranasal sinuses . with regard to the incidence of jof in the jaws a recent study by el - mofty identified two histopathological variants , trabecular jof ( trjof ) and psammomatoid jof ( psjof ) . one clinical feature that helps differentiate trjof from psjof is the site of involvement , with psjof occurring in the paranasal sinuses and trjof occurring in the maxilla . this makes our case report unique and rare , which reports a psammomatoid variant in mandibular region . a 20-year - old male patient reported to our unit with a complaint of swelling in the right lower jaw since 1 year . he has been evaluated at various places in his hometown , and previous biopsies reported were inconclusive . extraoral examination revealed a diffuse swelling present over the right lower third of the face which was hard and nontender on palpation with no localized rise in temperature ; there was no associated clinical lymphadenopathy . intraorally bony expansion of alveolus was present with obliteration of gingivobuccal sulcus [ figure 1 ] . orthopantomogram ( opg ) done 3 months prior to the presentation [ figure 2 ] showed a well - defined sharply demarcated border involving the roots of right side lower canine extending up to the first molar . however , opg at the time of presentation showed increase in radio - opacity as well as size of the lesion [ figure 3 ] . an incisional bone biopsy was done which showed lamellar bone along with islands of round to spindle - shaped cells displaying bland chromatin and eosinophilic cytoplasm , arranged in sheets . based on the biopsy report and clinical presentation , a provisional diagnosis of benign fibro - osseous lesion was made . due to the aggressiveness of the lesion , complete excision of the tumor was done , and the surgical defect was reconstructed with titanium reconstruction plate [ figure 4 ] . the surgical specimen on histopathology intraoral examination showed bony hard swelling with vestibular obliteration orthopantomogram done 3 months prior to presentation showing well - circumscribed mixed radio - opaque and radiolucent lesion involving the roots of premolar and first molar orthopantomogram at the time of presentation showed increase in the size of the lesion involving the canine and the second molar , highlighting the aggressiveness of the lesion postoperative orthopantomogram showing resection defect with adequate margin and reconstruction with titanium reconstruction plate juvenile aggressive ossifying fibroma ( jaof ) is a relatively rare fibro - osseous lesion of the jaw characterized by the early age of onset , the location of the tumor , radiological appearance , and high recurrent potentials . jaof may present as one of two histologic variants : juvenile psammomatoid ossifying fibroma ( jpof ) and juvenile trabecular ossifying fibroma . the psammomatoid type of jof is reported more commonly than the trabecular variety and is more aggressive with a strong tendency to recur . jpof occurs in young patients with peaks occurring in those who are above 15 years of age and is usually characterized by rapid growth and a high tendency for recurrence . the age of the patients ranges from 3 months to 72 years , with mean age of occurrence 17.7 years . the age and gender of the present case are in confinement of the data from literature . most cases affect sinonasal area and jaws ( 90% ) , out of which 10% cases involve mandible . in the jaw , the clinical and radiographic presentations of our patient were consistent with the features of jof with respect to the age , rapidly progressive nature , and the well - delineated radiographic picture . the imaging study of the present case showed a multilocular expansile lesion with a narrow transitional zone with the adjacent normal bone . these lesions usually presents with internal structure that can be radiolucent , mixed or radiopaque depending on the degree of calcification and presence of cystic areas . the present case demonstrated a mixed radio - opaque and lucent structure with resorption of the roots of the second molar . jpof is not capsulated but is separated from the surrounding bone by radiopaque borders , and this finding is helpful in differentiating it from fibrous dysplasia . it usually has a centrifugal growth pattern , which can lead to an erroneous clinical diagnosis of cemento - ossifying fibroma . other major conditions in the differential diagnosis include aneurismal bone cyst , osteoblastoma , osteosarcoma , and cemento - osseous dysplasia . burkitt lymphoma should also be considered in the differential diagnosis of jaof because of the similarity in the age and site of presentation , rapidity of growth , and radiolucent radiographic appearance . the aggressive nature of this entity with high rates of recurrence ( 3056% ) suggests that jpof should be treated with surgical resection , rather than conservative curettage . recurrence may be attributed to difficulty in proper resection caused by the location of the lesion and the infiltrative nature of the tumor borders . secondary reconstruction may be undertaken sooner for slow - growing lesions and be delayed for fast - growing lesions . although there are no cases of malignant transformation , rapidly growing lesions should raise suspicion and add a reason for delaying reconstruction . radiotherapy is contraindicated because of the risk of malignant transformation and potential harmful late effects in children . thus , appropriate recommended treatment is aggressive surgical approach followed by clinical and radiological follow - up . jaof is a rare , clinical entity often misdiagnosed and mismanaged because of its rapidly progressive and osteolytic nature . the diagnosis of psammomatoid variant of jof , especially when it affects structures other than the paranasal sinuses can be quite challenging as was seen in this case where the mandible was involved . joaf is treated by surgical excision and may recur if local resection is not complete . long - term follow - up is necessary owing to its locally aggressive nature and high recurrent potentials . a careful assessment of its clinical , radiographic , and histopathologic features is necessary to overcome the diagnostic and therapeutic challenges associated with this lesion .

the term juvenile ossifying fibroma ( jof ) is used in literature in naming two microscopically distinct fibro - osseous lesions of the craniofacial skeleton . one is characterized by small uniform spherical ossicles resembling psammoma bodies ( psammomatoid jof [ psjof ] ) . the other is distinguished by trabeculae of fibrillary osteoid and woven bone ( trabecular jof ) . psammomatoid ossifying fibromas represent a unique subset of fibro - osseous lesions of the craniofacial region . psjof has been distinguished because of its location , clinical behavior , and age of occurrence . they have distinctive histomorphologic features and a tendency toward locally aggressive behavior , including invasion and destruction of adjacent anatomic structures . it is generally seen in the younger age group , and the most common site is paranasal sinuses , orbits , and frontoethmoidal complex . we report a case of jpof involving mandible which is rarely been described in literature . an insight into the radiographic progression of this rare entity along with the clinical feature and surgical management is discussed .

congenital candidiasis ( cc ) is rare and usually caused by intrauterine candidial infection and manifests within first 6 days of life . it may be localized involving only skin or generalized resulting in respiratory distress , meningitis , sepsis , and death . a total of 10 - 35% of the women suffer from candidial vagintis during pregnancy , but less than 1% of them develop candidial chorioamnionitis that can affect the fetus . this is why cc is so rare and only 100 cases have been reported in the literature so far . a preterm ( 36 weeks ) , baby boy weighing 2.5 kg delivered by lower segment caesarean section ( lscs ) was brought to the dermatology department with pustular lesions all over the body on the second day of life . the attendant noticed erythema in both groins and over face within few hours after birth , followed by the appearance of pustular lesions on it in next 12 - 16 h. scalp , back of trunk , extremities , and palms were involved by the second day . mother was 31-year - old , gravida 6 , para 3 , live born 2 , abortions 3 , death 1[g6p3l2a3d1 ] with gestational hypertension . there was a history of cervical incompetence and cervical encirclage was done at 16 week of pregnancy . cutaneous examination revealed multiple , superficial , small pustules some coalescing to form lakes of pus over an erythematous back ground in groins , scalp , forehead , back , extremities , and palms . based on the history of vaginitis and cervical suture in the mother , whitish plaques on cord during delivery , pustular lesions on an erythematous background with in 24 h after birth , a clinical diagnosis of cc was considered . pustular lesions in groins pustules coalescing to form lakes of pus on the back hemogram revealed leucocytosis ( 24,900 cells / mm ) . koh mount from the pustular lesions revealed pseudohyphae suggestive of candidiasis [ figure 3 ] . culture on sabourauds dextrose agar showed candida species , further confirming the diagnosis [ figure 4 ] . the baby was given topical 2% ketaconazole cream twice daily along with fluconazole 6 mg / kg intravenously once daily for 3 days as there was leucocytosis . pustules began to dry by 3 day and desquamated completely by 5 day [ figure 5 ] . oral fluconazole ( 6 mg / kg / week ) and topical ketoconazole were continued for 1 week and there was no recurrence at 3 months of follow - up . cc is a very rare condition which presents at birth or with in first 6 - 7 days after birth and generally represents maternal chorioamnionitis occurring either from birth canal as an ascending infection or as transplacental infection . ascending infection may occur either from subclinical rupture of membranes or even through intact membranes resulting in whitish plaques on the membranes and umbilical cord along with skin lesions , described classically as various risk factors like < 27 weeks of gestation age , wt < 1000 g , intrauterine device , cervical sutures , invasive procedures , and extensive instrumentation have been reported . the role of maternal steroids or immunodeficiency in the infant is controversial . in the present case , cervical encirclage was done for cervical incompetence by mcdonold 's method at 16 weeks of pregnancy . cc manifest at birth or within a few hours of birth as extensive erythematous maculopapular eruption on head , trunk , and extremities that progress to vesicles and pustules on erythematous base in 1 - 3 days . palmar and plantar pustules are considered as hallmark of the disease , but mucosae and napkin area are spared . onychia and paronychia may occur and rarely cc may be limited to nails . scalded or burn - like appearance of skin lesions may herald systemic involvement . severe involvement of gastrointestinal and respiratory tract can occur due to aspiration of infected amniotic fluid that culminates in candidial septicemia manifesting as bronchopneumonia , meningitis , arthritis , endocarditis with microabcess in liver , brain , kidneys , or spleen . features like respiratory distress , leucocytosis with left shift , persistent hyperglycemia , glycosuria , positive cultures from blood , urine , cerebrospinal fluid ( csf ) , and burn - like skin lesions suggest systemic involvement . neonatal candidiasis typically manifests after 6 days of life and differs clinically from cc [ table 1 ] . cc should be differentiated from various other diseases presenting with pustules in the newborn [ table 2 ] . comparision of congenital and neonatal candidiasis causes of neonatal pustular disorders diagnosis was established by koh mount of skin lesions showing budding yeasts and pseudohyphae and culture revealing candidial growth . blood , urine , and csf cultures should be obtained to rule out systemic involvement if there is clinical suspicion . amphotercin b is the first line agent given in doses of 0.5 - 1 mg / kg / day and liposomal amphotericin b is less toxic and preferred if there is preexisting renal insufficiency . fluconazole at 6 - 12 mg / kg / day dose is effective alternative if organism is susceptible . topical therapy is given till the resolution of skin lesions and systemic therapy continued for minimum of 21 - 28 days if systemic involvement is present . cc is very rare and needs to be differentiated from various diseases presenting with generalized maculopapular or pustular lesions at birth in order to avoid complications .

congenital candidiasis ( cc ) is a rare disease with less than 100 cases being reported in the literature . it presents within six days of life with manifestations ranging from localized skin disease to systemic involvement in the form of respiratory distress , sepsis , and death . we report a neonate who presented with diffuse pustular eruption on erythematous background involving face , trunk , and palms within 24 h after birth . candida albicans was identified in 10% potassium hydroxide ( koh ) smear and culture from the pustules . intravenous fluconazole and topical ketoconazole were given and the condition improved completely in two weeks . cc is rare and needs to be differentiated from other conditions presenting with pustular lesions at birth in order to avoid complications . early diagnosis and prompt treatment of this condition is important as untreated cases carry a mortality rate of 8 - 40% .

inflammatory myofibroblastic tumor ( imt ) is a rare tumor involving different organs , with lung being one of them . we report a case of imt that was successfully treated with bronchoscopic resection and also review the available literature . to the best of our knowledge , this is the first case report of successful resection of endobronchial imt from the indian sub - continent . a 32-year - old patient , non - smoker and without any known co - morbidity , presented with complaints of recurrent hemoptysis for the last 2 - 3 years . his physical examination was unremarkable and chest x - ray did not show any abnormalities . a contrast - enhanced computed tomography ( cect ) of the thorax was performed [ figures 1 and 2 ] , which revealed an eccentric , well - defined homogenous lesion arising from the right bronchus intermedius just distal to the origin of the upper lobe bronchus ( dimensions of 2 cm 1 cm 1 cm ) . fiber - optic flexible bronchoscopy showed the mass ( of the size mentioned above ) almost obstructing the intermediate bronchus of the right side [ figure 3 ] . an endobronchial biopsy was undertaken and sent for histopathological examination , which showed sheets of plasma cells admixed with few histiocytes and lymphocytes suggestive of imt [ figure 4 ] . on immuno - histochemistry , the plasma cells showed positive staining for syndecan , with both kappa and lamda positive cells ; which was compatible with imt . contrast - enhanced computed tomography of the thorax ( axial cut ) showing the tumor in the intermediate bronchus of the right lung contrast - enhanced computed tomography of the thorax ( coronal cut ) showing the tumor in the intermediate bronchus of the right lung bronchoscopic view showing the tumor before the procedure histopathology of the tumor demonstrating sheets of plasma cell , histiocytes and lymphocytes typical of inflammatory myofibroblastic tumor a review of the literature was undertaken to determine the most appropriate line of management . as the lesion was endobronchial , it was decided to endoscopically resect the tumor . under general anesthesia , a ventilating rigid bronchoscope ( wolf ventilating bronchoscope of size 8 mm 400 mm ) was inserted . a fiberoptic bronchoscope ( fob ) ( outer diameter of 5.9 mm ) then , a snare forceps was inserted through the fob and the protruding portion of the tumor was grasped and elecrtocauterized . the remaining portion of the tumor was removed with the assistance of a toothed forceps and electrocautery . removal of the whole tumor was achieved [ figure 5 ] and hemostasis was secured . the patient was followed - up clinically and bronchoscopy was repeated at a 2-month interval . the patient did not have any recurrence of hemoptysis and the repeat bronchoscopies were normal ( at 2 , 4 and 7 months ) [ figure 6 ] . bronchoscopy after the procedure demonstrating almost complete removal of the tumor bronchoscopy 7 months after the procedure showing no signs of recurrence imt is defined by the world health organization as a distinctive lesion composed of a myofibroblastic spindle cell population accompanied by an inflammatory infiltrate of plasma cells , lymphocytes and eosinophils . it has been known by different names like inflammatory plasma cell granuloma , pseudotumor , fibroxanthoma , xanthofibroma , xanthoma , xanthogranuloma , etc . it can involve different systems like the lung , eye , gastrointestinal tract , etc . , although considered the most common primary lesion of the lung in children under 16 years of age , overall , across all age groups , it is one of the rarest lung tumors with an incidence varying from 0.04% to 0.7% . some authorities attribute it to non - neoplastic processes like metabolic disturbance , viral origin or antigen antibody interaction to an unidentifiable agent , while some others attribute it to neoplastic processes . the clinical presentation of the tumor can be variable , ranging from asymptomatic ( 70 - 78% ) to symptoms like cough , hemoptysis , chest pain , dyspnea , fever , etc . , radiology of the chest is helpful in localizing the position , which can involve any lobe or segment . it is usually solitary , although multiple lesions involving the same or different lobes of the ipsilateral of contralateral lung may be found . for clinching the diagnosis , needle biopsy , wedge biopsy or resectional biopsy the natural history of imt is variable . it may remain stable or grow slowly over time or regress . in some cases , it may also show invasiveness and involve the mediastium , diaphragm , chest wall , vertebral bodies , etc . the treatment of imt usually entails complete surgical resection of the tumor , either by video - assisted thoracoscopy or open thoracotomy . larger lesions and those with an evidence of local invasion of the surrounding tissues will require a thoracotomy . obtaining a tumor - negative margin is important to determine the extent of resection . for cases where the disease is deemed unresectable ( multiple nodules or extensive involvement ) , or the patient is medically inoperable , there are sporadic reports of success with corticosteroids , radiotherapy or chemotherapy . evidence regarding management of tracheobronchial imt is deficient as very few case reports of such cases exist in the literature . a search was carried out using the pubmed , medline and embase databases to identify cases where imt of the tracheobronchial tree has been bronchoscopically treated ( table 1 shows the list of such cases ) . all the cases involved patients who were relatively young , with a mean age of 26 years ( range 16 - 45 years ) . the majority of the patients belonged to the female gender ( 4 out of 6 , in one case the gender was not specified ) . in 43% of the cases ( 3/7 ) the tumor was confined to the trachea , in 28.5% of cases ( 2/7 ) in one of the main bronchus while 28.5% of the cases ( 2/7 ) had lesions both in the trachea and in the bronchus . the major presenting symptom was dyspnea ( 3/7 or 48% cases ) , followed by recurrent pneumonia , cough and hemoptysis ( 2/7 or 28.5% cases ) . in all the cases , rigid bronchoscopy was employed and in one case nd yag laser was used . in 57% of the cases ( 4/7 ) , post - operative steroids were used . bronchoscopic resection is thus a viable alternative in cases of imt confined to the tracheobronchial tree . although large - scale trials are required to compare the relative efficacy of bronchoscopic resection vis - a - vis surgical resection , it can be appreciated that enrollment of sufficient cases would be difficult given the rarity of this entity .

inflammatory myofibroblastic tumour ( imt ) is a rare tumour affecting the tracheo - bronchial tree in the adult population . the clinical presentation of this tumour is diverse and diagnosis can be definitively clinched by histopathological examination . treatment of this tumour usually requires surgical resection with bronchoscopic resection being described in few cases . we describe a 32 year old male presenting with hemoptysis who was diagnosed to have imt . resection of the tumour was done with the help of rigid bronchoscopy . post - resection , hemoptysis stopped and no recurrence of tumour was noted on subsequent follow - up . we also present a systematic review of literature of all the cases of tracheo - bronchial imt treated with bronchoscopic resection and conclude it to be a useful alternative to surgery in such cases .

recently , seok et al.1 described a successful correction of post - traumatic anterior open bite via injection of botulinum toxin type a ( btx - a ) into the anterior belly of the digastric muscle ( abdm ) in a 20-year - old man with malocclusion and wound dehiscence in the left retromolar area . in the case of mandibular angle fractures , the digastric muscles depress the anterior fragment2 ; therefore , by paralyzing the musculature , seok et al.1 were able to mitigate the forces displacing the anterior mandible . a ) , that the btx - a injections were placed in bilaterally symmetrical anterior digastric musculature that was unremarkable with regard to anatomical variation . abdm is typically considered to be bilaterally symmetrical ; however , abdm muscular variants have been reported to occur in as much as 69.9% of the population3 . diverse anatomical variations of the abdm have included duplications , triplications , and quadrifications , in addition to exotic fractal and weave patterns of musculature45678 . also , abdm has been reported to cross the midline and insert contralaterally 5 . therefore , the existence of variant abdm should be taken into consideration when attempting to reduce fractures of the mandible . an example of a variant abdm that may complicate btx - a injection is shown in fig screening for anatomical variation of anterior digastric musculature with ultrasound ( us ) , computed tomography ( ct ) , and/or magnetic resonance imaging ( mri ) should be performed in order to adequately plan injection of btx - a into anterior digastric musculature . upon imaging with us , skin can be marked directly over the digastric musculature in order to identify injection sites as variant musculature is encountered . with ct and mri , bony references , such as the mandible and hyoid , can be used to calibrate measurements corresponding to the location of the musculature , which can subsequently be used to mark injection sites on the submental skin . in light of their success in the treatment of the patient who responded favorably to btx - a injection into the abdm for the treatment of anterior open bite , seok et al.1 recommended a large - scale , case control study in which btx - a injection is applied to selective open bite patients who do not respond to extensive rubber traction . while such a study might be prudent , it is important to recognize the diversity of abdm musculature when planning btx - a injection for the management of anterior open bite , in order to avoid undesired effects . botulinum toxin injected in the neck can produce weakness of the neck flexors and dysphagia9 ; however , the majority of adverse effects due to botulinum toxin injections include bruising , edema , pain at the injection site , and flulike symptoms 91011 . the more serious side effects of injection typically result from improper needle placement due to a lack of understanding of the underlying anatomy and physiology , subsequently allowing the neurotoxin to either diffuse or be inadvertently injected into adjacent musculature91011 . there are obvious differences among these imaging techniques with regard to cost , time , and invasiveness ; however , to the author 's knowledge , no reports have specifically compared these techniques with regard to proper identification or characterization of anterior digastric musculature . screening for variant abdm should be performed prior to btx - a injection into the anterior digastric musculature in order to account for muscle variations that may result in undesired forces on the anterior mandible in patients with anterior open bite and to prevent undesired adverse effects of btx - a injection .

it has recently been reported that long - standing post - traumatic open bite can be successfully corrected with botulinum toxin type a ( btx - a ) injection into the anterior belly of the digastric muscle ( abdm ) . the report documented an individual with bilaterally symmetrical and otherwise unremarkable anterior digastric musculature . however , the existence of variant anterior digastric musculature is common and may complicate the management of anterior open bite with btx - a injection . screening for variant abdm can be accomplished via ultrasound , computed tomography , and magnetic resonance imaging . screening for variant abdm should be performed prior to btx - a injection in order to account for musculature that may exert undesired forces , such as inferolateral deviation , on the anterior mandible in patients with anterior open bite .

oncocytes are observed in lesions of several organs such as the thyroid , kidney , pancreas , ovary , liver , and salivary gland . in the salivary glands , oncocytes are known to arise in warthin tumor , oncocytoma , oncocytic carcinoma , and oncocytosis . oncocytosis is a rare non - neoplastic lesion that is classified as diffuse oncocytosis and multifocal adenomatous oncocytic hyperplasia ( maoh ) ; it comprises approximately 0.1% of salivary gland lesions [ 3 , 4 ] . the correct cytological diagnosis of oncocytosis can be difficult because oncocytes are seen in a variety of other salivary gland lesions , and it is usually diagnosed by histological examination [ 5 , 6 , 7 , 8 ] . here she consulted an otolaryngology clinic because of discomfort at the left side of her neck . at the clinic , a mass was noted in the left side of her neck and she was referred to our hospital . a 1.5-cm mass with no lymph node swelling was identified using magnetic resonance imaging . from the above clinical findings , warthin tumor or a malignant parotid tumor was suspected . five slides were prepared for cytological evaluation , including 3 fixed smears for papanicolaou staining , 1 air - dried smear for may - grnwald giemsa ( mgg ) staining , and 1 smear examined by liquid - based cytology ( lbc ) based on the lbc technique . papanicolaou staining of direct smears revealed a loose sheet - like cluster formed of round to polygonal cells with granular cytoplasm against a hemorrhagic background . the cells had round to oval , centrally located nuclei with granular chromatin and without distinct nucleoli . in the lbc preparation , the cytoplasm showed microvacuoles in contrast to the direct smear ( fig . there were only a few lymphocytes , and basophils were not detected in any of the smears . the cut surface of the resected lesion revealed a milky - white lobular mass with an unclear border ( fig . microscopically , the lesion was formed of many variable - sized nodules that comprised oncocyte - like cells with small round nuclei and eosinophilic granular cytoplasm . a definite capsule was not seen around the nodules and the surrounding adipose tissue and acinus . the oncocyte - like cells were diffusely positive for cytokeratin antibodies and strongly positive for mitochondrial antibodies ( fig . basophils were not detected in the lesion , using immunohistological staining based on anti - cd117 ( c - kit ) antibodies . typical findings for low - grade cancer of the salivary glands were not observed . from the above findings it has been reported that maoh develops in women in their 60s and is localized unilaterally in the parotid glands . histologically , maoh is thought to arise from the ductal epithelium and the remnants of the original salivary gland . the lesion was observed unilaterally in the left parotid gland in a 71-year - old woman . the remnants of the existing salivary ducts were observed by p63 and ck34e12 staining , and a strong response to mitochondrial antibodies was found in the cytoplasm . from the above findings described the cytological findings of maoh in a case report : ( 1 ) a low n / c ratio ; ( 2 ) central round nuclei ; ( 3 ) anisonucleosis ; ( 4 ) prominent nucleoli ( in part of the cells ) , and ( 5 ) abundant eosinophilic cytoplasm . in the present case , however , we could not make a diagnosis of maoh cytologically because of the high n / c ratio and because the nucleoli were unclear . cytologically , the major lesions in which oncocytes are observed include warthin tumor , oncocytoma , and oncocytic carcinoma . typical cytological findings of warthin tumor reveal oncocytes and lymphocytes with an inflammatory or necrotic background . have reported that mast cells are present with oncocytes in fine - needle aspiration preparations . kobayashi et al . have investigated the frequency of mast cells in cytological samples , as compared with immunocytochemical identification using human mast cell tryptase antibodies in warthin tumor , and have indicated that mast cells are frequent in the epithelial cell component . in contrast , there are no reports to suggest any association with mast cells of other lesions . we also searched for mast cells by cytological mgg staining and immunohistochemical staining using the cd117 ( c - kit ) antibody . . the identification of basophils seems to be a diagnostic checkpoint when differentiation from warthin tumor is necessary . however , the typical cytological findings such as a lymphocyte and/or basophil appearance were not observed in any of the cases , which may thus be mistakenly diagnosed as oncocytoma or maoh . cytological features of oncocytoma comprise large , round to polygonal cells with abundant granular cytoplasm , centrally located nuclei , prominent nucleoli , binucleation , sheet - like clustering , and an often necrotic background . in oncocytic carcinoma , although the neoplastic cells are pleomorphic , with nuclear atypia and hyperchromatism , other findings overlap with oncocytoma [ 7 , 8 , 13 ] . thus , it can be difficult to differentiate between maoh , warthin tumor , and oncocytoma . in addition , a case of oncocytoma arising from maoh has been reported . however , the distinction between maoh and oncocytoma is possible by capsular interpretation . therefore , it should be noted that neoplastic identification can not be achieved from partial samples microscopically . furthermore , oncocytic metaplasia has recently been shown in other salivary gland lesions ( e.g. , pleomorphic adenoma , myoepithelioma , and mucoepithelial carcinoma ) , except for maoh , warthin tumor , and oncocytic tumor . therefore , it is necessary to carefully carry out the assessment of oncocytes . when oncocytes are observed , it is necessary to perform a surgical resection . the authors have no potential conflicts of interest with respect to the authorship and/or publication of this article .

multifocal adenomatous oncocytic hyperplasia ( maoh ) is a non - neoplastic lesion that is classified as oncocytosis . maoh is a rare entity of the parotid gland and accounts for approximately 0.1% of salivary gland lesions . here , we report a case of maoh of the parotid gland . the patient was a 71-year - old woman who presented with discomfort at the left side of her neck . fine - needle aspiration cytology of the parotid gland revealed a loose sheet - like cluster of round to polygonal cells with granular cytoplasm against a hemorrhagic background . the cells had round to oval , centrally located nuclei with granular chromatin and without distinct nucleoli . histologically , the lesion was formed of many variable - sized nodules , comprising oncocyte - like cells with small round nuclei and eosinophilic granular cytoplasm that was positive for mitochondrial antibodies . the diagnosis of maoh is difficult to make by cytology alone , because the findings overlap with those of other oncocytic lesions . in particular , the cytological findings of maoh have not been sufficiently reported to date . a correlation of cytology and histology was expected .

traumatic abdominal wall hernia ( tawh ) associated with blunt injury mechanism is very rare , with an approximate prevalence of 0.21% in major reported series.[14 ] abdominal evisceration ( ae ) associated with tawh is even less common , with one study reporting an incidence of approximately 1 in 40,000 trauma admissions . while the precise mechanism behind tawhs is not fully understood , they are thought to result from simultaneous surge in abdominal pressure and the presence of shearing forces that synergistically lead to the disruption of the abdominal wall musculature and fascial layers . this report describes a case of ae an example of the most extreme clinical manifestation of tawh following blunt traumatic abdominal wall injury . the authors also review literature on abdominal wall injury grading in the context of the clinical problem presented herein . a middle - aged female presented to a level i trauma center after being involved in a horse riding accident . the patient was thrown off the horse , which then fell and rolled partially onto the patient . during the process , the horn of the saddle briefly exerted direct pressure on the patient 's lower abdomen before the horse recovered . initially awake and alert , the patient became progressively more somnolent , requiring endotracheal intubation at the scene . en route to the hospital , the patient was noted to have a loop of small bowel protruding from an open lower abdominal wound . the bowel was easily reduced and saline - soaked gauze was used for temporary coverage over the wound . upon arrival to the trauma bay , her pulse rate was 92 beats / minute and the blood pressure was 164/86 mmhg . the patient 's glasgow coma score was 10 t ( motor 6 , verbal 1 t , eyes 3 ) during the initial trauma bay evaluation . on further examination , she was found to have a 10-cm transversely oriented complex suprapubic abdominal wound [ figure 1a ] . upon reflection of the superior skin flap , the wound was found to involve full thickness of the abdominal wall as well as evisceration of bowel loops [ figure 1b ] . other positive findings on the physical exam included superficial skin abrasions and lower back pain . there was also trace hematuria present on urinalysis performed upon placement of urinary catheter , with no other signs of urinary system injury . given continued hemodynamic stability , computed tomography ( ct ) was performed to rule out any potential associated skeletal and head injuries . the patient was then taken to the operating room for exploratory celiotomy , abdominal washout , and repair of the tawh . ( a ) note the symmetric butterfl y - shaped defect , with the bowel not immediately apparent . ( b ) after lifting the upper wound fl ap , bowel evisceration became evident in the operating room , the peritoneum was entered through a midline incision separate from the original traumatic suprapubic wound [ figure 1a and b ] . the bowel , abdominal solid organs , and the retroperitoneum were inspected , with no additional injuries found . subsequent examination of the tawh showed the anterior abdominal fascia not amenable to complete primary reconstruction due to severe tissue fragmentation / disruption . therefore , the patient 's native fascia was closed using a combination of biologic mesh underlay combined with primary suture repair ( where possible ) . subsequent layered closure of the wound was performed and the patient was taken to the surgical intensive care unit . the patient was discharged from the hospital 1 week after the initial injury and did well in follow - up at 6 months , both from a cosmetic and a functional perspective . the patient returned to pre - injury activity levels and there was no evidence of recurrent hernia at the site of the traumatic defect . tawhs associated with blunt injury mechanisms are uncommon , with an approximate prevalence of 1% in major reported series.[148 ] tawhs have been linked to both high energy ( i.e. , traffic / pedestrian accidents , falls from a height ) and low energy ( i.e. , handlebar hernia ) mechanisms consistent with the mechanism reported in the current case , many tawhs have been associated with the victim impacting on angled or curved surfaces / objects . tawhs are thought to result from simultaneous surge in abdominal pressure and the presence of shearing forces that synergistically disrupt the abdominal wall musculature and fascial layers . associated aes are even less common , accounting for approximately 1 in 40,000 trauma admissions . aes constitute an extreme form of tawhs , with the main difference between the two being the amount of force that is focally delivered to the abdominal wall tissues , as well as the anatomic location of the force application ( i.e. , eviscerations tend to occur at anatomically weak points the lateral rectus , lower abdomen , and inguinal regions ) . due to the mechanism of injury and significant forces required to cause both tawh and ae , further investigation to rule out other intra- and extra - abdominal associated injuries is required . if the patient is hemodynamically stable , a ct scan is the preferred modality for diagnosis of any potential associated injuries . the incidence of associated intra - abdominal injuries among patients with tawh may be as high as 30% . dennis et al . described an abdominal wall injury scale based on ct scan findings , with overall injury severity graded on a scale from i to vi [ table 1 ] . of note , among the 140 patients with ct - diagnosed abdominal wall injuries in that study , only 3 had tawh ( grade v injury ) and none of the patients had grade vi injury ( i.e. , complete abdominal wall disruption with evisceration ) . abdominal wall injury grading scale regardless of the presence of any associated injuries , prompt surgical repair of the tawh and/or ae it is still required . at the time of surgical repair , the surgeon should perform a standard trauma laparotomy via separate midline abdominal incision , followed by either mesh and/or primary repair of the traumatic abdominal wall defect . at times , immediate abdominal wall reconstruction may not be possible and staged abdominal wall closure may be required . long - term follow - up is needed to ensure that both cosmetic and functional outcomes are satisfactory . it is also important to monitor the patient for the possibility of a recurrent hernia at the injury site . when encountered , blunt tawh / ae should prompt an aggressive search for other associated injuries and prompt surgical repair of the abdominal wall defect . in more severe cases , staged abdominal wall closure / reconstruction may be required . long - term follow - up is important and should include the assessment of cosmetic and functional outcomes as well as examination for any recurrent herniation at the site of the injury . the tawh / ae outlined herein represents one of the very few cases of grade vi abdominal wall injury in the world literature .

blunt traumatic abdominal wall disruptions associated with evisceration are very rare . the authors describe a case of traumatic abdominal wall disruption with bowel evisceration that occurred after a middle - aged woman sustained direct focal blunt force impact to the lower abdomen . abdominal exploration and surgical repair of the abdominal wall defect were performed , with good clinical outcome . a brief overview of literature pertinent to this rare trauma scenario is presented .

in this issue of critical care , totapally et al . evaluated the effect of albuterol on tidal breathing loops of 20 infants with respiratory syncytial virus ( rsv ) bronchiolitis . they found that the wheeze score and the pulmonary function tests were not significantly affected by albuterol . this is the latest of 12 randomised controlled trials in 12 years , involving 843 infants , that evaluated the effect of bronchodilators on bronchiolitis . after so many trials , have we resolved whether bronchodilators have a role in the management of bronchiolitis , and have pulmonary function measurements been helpful ? of the 12 most recent randomised controlled trials published in english , evaluating the effect of salbutamol or albuterol on bronchiolitis , nine ( 75% ) showed that bronchodilators had no effect . in three of these studies , some difference had been observed , yet it resulted in only a small transient improvement in the acute clinical score and had no effect on hospital admission rates or duration of stay in hospital . in one of these three studies , ex - premature infants who might have had some mild underlying chronic lung disease , which might have resulted in the response to bronchodilators , were not excluded . several studies reported an increase in heart rate or a decrease in oxygen saturation after salbutamol or albuterol . the effect of ipratropium bromide ( either alone or in combination with salbutamol or albuterol ) on bronchiolitis has been evaluated in four recent randomised controlled trials and none has shown any significant effect . in contrast , there have been five published randomised controlled trials in the last 10 years , involving 225 infants , evaluating the effect of nebulised adrenaline ( epinephrine ) on bronchiolitis . all five ( 100% ) have shown significant clinical improvement in infants with bronchiolitis , with decreases in oxygen requirement , respiratory rate , wheeze and retractions . the incidence of side effects is no more frequent with nebulised adrenaline than with salbutamol . the 90-minute heart rate was often significantly lower in the adrenaline group , and although pallor was noted more frequently it was transient and of no known clinical significance . these results suggest that mucosal swelling and mucous plugging make a greater contribution to the increased airway resistance observed in bronchiolitis than constriction of bronchial smooth muscle . barr et al . found a beneficial effect of inhaled adrenaline in an infant with rsv bronchiolitis who was also receiving -adrenergic receptor blockade with propranolol . this indicates that it was most probably the -adrenergic stimulation that was improving airway obstruction by inducing arteriolar vasoconstriction in the airway mucosa and thus reducing bronchial mucosal thickness . of the 12 randomised studies evaluating the effect of bronchodilators on bronchiolitis , only in those by totapally et al . and sly et al . were any pulmonary function measurements made . totapally used tidal breathing flow - volume loops to assess the effect of albuterol on infants with bronchiolitis , and they found no significant change . two main calculations were made : the exhaled time to reach peak expiratory flow as a fraction of total expiratory time ( tptef / te ) and the tidal volume exhaled at peak tidal expiratory flow as a fraction of total tidal volume ( vptef / ve ) . the time needed to reach peak tidal expiratory flow is highly influenced by the activity of the laryngeal abductors and adductors , abdominal and intercostal expiratory muscles , post - inspiratory activity of the diaphragm and intercostal muscles , and vagal nerve tone . changes in these muscle activities could cause significant alterations in tptef / te independently of changes in the resistance and compliance of airways and lung . thus tptef / te is an insensitive measure of airway function in infants and children in comparison with vmaxfrc ( maximal flow at functional residual capacity produced by forced expiration as a result of a rapid chest compression ) and other more invasive techniques . sly et al . performed a randomised trial of salbutamol in infants with bronchiolitis and measured vmaxfrc and found no significant change . sanchez also conducted pulmonary function tests in a crossover trial comparing salbutamol with racemic adrenaline . as in other studies , administering salbutamol resulted in no change , whereas adrenaline significantly decreased pulmonary resistance . sanchez et al . used a more invasive technique , measuring transpulmonary pressures ( with an oesophageal catheter ) , flow and volume to determine pulmonary resistance by a least - mean - square technique . they excluded breaths in which the leak was greater than 10% , the correlation coefficient was less than 0.95 or the tidal volume was less than 0.5 ml / kg , to eliminate the analysis of shallow breaths and artefacts . leaks around the mask or around an uncuffed endotracheal tube can cause major errors in the pulmonary function measurements and lead to gross overestimation of compliance and resistance . the inspired and expired volumes need to be within 10% of each other to allow an accurate analysis . ideally , absolute lung volume should also be measured to help in the interpretation of resistance changes ; however , this is invasive and difficult to perform . although totapally et al . should be commended for performing pulmonary function measurements to assess further the effect of albuterol on infants with bronchiolitis , the pulmonary function results need to be interpreted with a degree of caution . however , in view of the general lack of effect of bronchodilators in bronchiolitis in other studies , i do not think that any significant effect of albuterol on pulmonary function was missed in this study . it also highlights the urgent need for a simple non - invasive test that can measure lung function in infants more accurately . in summary , there is no compelling evidence that bronchodilators have a role in the routine management of infants with bronchiolitis . there is better evidence for the use of nebulised adrenaline , which results in a reduction of the airway mucosal oedema , leading to symptomatic improvement , improved pulmonary function and shorter hospital admissions . rsv = respiratory syncytial virus ; tptef / te = exhaled time to reach peak expiratory flow as a fraction of total expiratory time ; vmaxfrc = maximal flow at functional residual capacity produced by forced expiration as a result of a rapid chest compression ; vptef / ve = tidal volume exhaled at peak tidal expiratory flow as a fraction of total tidal volume .

over the past 12 years there have been 12 randomised control trials , involving 843 infants , evaluating the effect of salbutamol or albuterol on bronchiolitis . of these , nine ( 75% ) showed that bronchodilators had no effect . in three studies a small transient improvement in the acute clinical score was seen . ipratropium bromide had no significant effect . there have been five recent randomised trials involving 225 infants , evaluating the effect of nebulised adrenaline ( epinephrine ) on bronchiolitis . all five ( 100% ) have shown significant clinical improvement , with reductions in oxygen requirement , respiratory rate and wheeze after nebulised adrenaline . two showed lower hospital admission rates and earlier discharge with adrenaline . a significant improvement in pulmonary resistance was observed after nebulised adrenaline but not after salbutamol or albuterol . currently there is no compelling evidence that bronchodilators have a role in the routine management of infants with bronchiolitis . there is better evidence for the use of nebulised adrenaline .

a 39-year - old man developed an 8 7-cm hypopigmented and centrally atrophic plaque with erythematous indurated borders in an area of scar tissue on his forehead ( fig . 1a ) . on the occipital scalp he presented an erythematous brownish plaque resulting in cicatricial alopecia , as well as multiple brownish patches and papules on the trunk and shins . skin biopsies from forehead , scalp and the pretibial area showed inflammatory non - caseating granulomas ( fig . chest x - ray revealed bilateral hilar adenopathy , nodules and reticular opacities , while pulmonary function tests indicated an obstructive ventilation disorder with physiologic diffusion capacity for carbon monoxide . prior to presentation , topical tacrolimus , systemic prednisolone , chloroquine , isotretinoin and acitretin had been unsuccessful . at our department , subsequently , adalimumab was started at 80 mg as a first dose and then at 40 mg every second week . methotrexate was stopped after 1 month of overlapping therapy due to elevated transaminases . within 4 months the disfiguring forehead plaque regressed and flattened out , enabling camouflage of the remnant skin changes ( fig . the subjective disease activity as measured by the visual analogue scale score decreased from 7/10 to 3.5/10 points within 4 months , and the dermatology life quality index ( dlqi ) dropped from 16/30 to 3/30 . a follow - up biopsy of the border of the forehead lesion revealed almost complete clearance of lymphocytic infiltrates and complete absence of granulomas . tnf antagonists have proven useful and safe for a number of cutaneous diseases such as psoriasis and pyoderma gangrenosum . for sarcoidosis , tnf- targeting has been found to be effective in isolated cases . because inflammatory granulomas depend on tnf- signaling , there is a rationale for its blockade . even before biologics became available , thalidomide a compound with anti - tnf- activity had been used successfully . an extent that would not qualify for biologic therapy , had he , for example , suffered from psoriasis . however , due to the intense impairment of quality of life by the disfiguring plaques as measured by dlqi , as well as because of pulmonary sarcoidal affection , the decision to use a biologic was deemed reasonable and reimbursable by the patient 's health insurance . whether this strategy should be adopted for all patients with sarcoidosis and would be affordable , tnf - blocking agents may be superior to most treatments described for sarcoidosis such as steroids , methotrexate , thalidomide , antimalarials , azathioprine , cyclosporin a , leflunomide and cyclophosphamide . interestingly , as described for psoriasis , tnf antagonists have been reported to not only treat , but also induce cutaneous or systemic sarcoidosis . taken together , in selected cases , tnf- inhibition may be beneficial for the treatment of cutaneous sarcoidosis with or without systemic involvement . funding / support : this study was supported by the department of dermatology , university hospital of zrich . financial disclosure :

depending on the location , dermatoses can produce blemishes that severely impair quality of life and require highly effective treatment that is otherwise used for extensive skin involvement . we report the case of a 39-year - old , otherwise healthy male disfigured by an 8 7-cm hypopigmented and centrally atrophic annular plaque with erythematous indurated borders in an area of scar tissue on his forehead . skin biopsies revealed non - caseating granulomas , and hilar involvement was identified , leading to the diagnosis of systemic sarcoidosis stage ii with cutaneous involvement . the lesions proved resistant to multiple therapies , but responded within 4 months to adalimumab with regression of the lesion and inflammatory infiltrate . the visual analogue scale of disease activity decreased from 7/10 to 3.5/10 , and the dermatology life quality index from 16/30 to 3/30 points . in conclusion , tnf- inhibition can control inflammation and disfigurement by cutaneous sarcoidosis and restore quality of life .

the transcriptome of medullary stromal cells of patients suffering from primary myelofibrosis was studied by agilent oligo microarray technology . the primary myelofibrosis is a chronic myeloproliferative syndrome . to invest the role of bone marrow stroma in the pathophysiology of this disease , we isolated primary cultured of bone marrow stromal cells from these patients . the osteo - medullary biopsies for the diagnosis of the disease were implanted in dmem medium with 10% fetal calf serum . stromal cells during their proliferation adhere to plastic and they were trypsinized between each passage ( 35 passages ) when cultures came to confluence . a cytometric control was carried out on the cells prior to performing molecular biology experiments . cd105 , cd73 and cd90 marker positivity was verified to validate the mesenchymal cell phenotype . the negativity of the cd45 marker was also carried out to prove the absence of residual hematopoietic cells in culture . each culture of mesenchymal stromal cell is isolated from the bone marrow of an individual . in total , the bone marrow samples were studied individually from 6 healthy donors ( 6 controls : gsm1084994 , gsm1084995 , gsm1084996 , gsm1084997 , gsm1084998 , gsm1084999 ) and from 6 patients with primary myelofibrosis ( 6 pmf : gsm1085000 , gsm1085001 , gsm1085002 , gsm1085003 , gsm1085004 , gsm1085005 ) . concerning the enrollment of control samples : subjects are negative for alcohol abuse and hcv , hbv and hiv virus infections . the choice of control subjects was conditioned by access to bone marrow from subjects having a hip prosthesis surgery : indeed the subjects have an average age similar to that of patients with primary myelofibrosis ( between 60 and 80 years ) . each sample was treated individually for the extraction of nucleic acids and the achievement of microarrays . rna was isolated using rna extraction protocols ( nucleospin rna ii , macherey - nagel ) on the miltenyi plateform . rna samples were quality - checked via the agilent 2100 bioanalyzer ( agilent technologies ) . total rna sample ( 1 g ) rna samples were amplified and labeled using the agilent quick amp labeling kit / low rna input linear amp kit ( agilent technologies ) . the hybridization procedure was performed using agilent gene expression hybridization kit ( agilent technologies ) . briefly , 1.65 g cy3-labeled fragmented crna in hybridization buffer was hybridized overnight ( 17 h , 65 c ) to agilent whole human genome oligo microarrays 4 44k using agilent 's in hybridization chamber . the fluorescence signals were detected using agilent 's microarray scanner system ( agilent technologies ) . the agilent feature extraction software ( fes ) v9.1 was used to read out and process the microarray image files . the signal intensities from single experiment raw data lists are normalized by dividing the intensities values by their median . normalized data were accessible on public database : ( geo submission number gse44426 , http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=gse44426 ) , online on jan . 10 , 2015 ) , .

primary myelofibrosis ( pmf ) is a clonal myeloproliferative neoplasm whose severity and treatment complexity are attributed to the presence of bone marrow ( bm ) fibrosis and alterations of stroma impairing the production of normal blood cells . despite the recently discovered mutations including the jak2v617f mutation in about half of patients , the primitive event responsible for the clonal proliferation is still unknown . in the highly inflammatory context of pmf , the presence of fibrosis associated with a neoangiogenesis and an osteosclerosis concomitant to the myeloproliferation and to the increase number of circulating hematopoietic progenitors suggests that the crosstalk between hematopoietic and stromal cells is deregulated in the pmf bm microenvironmental niches . within these niches , mesenchymal stromal cells ( bm - msc ) play a hematopoietic supportive role in the production of growth factors and extracellular matrix which regulate the proliferation , differentiation , adhesion and migration of hematopoietic stem / progenitor cells . a transcriptome analysis of bm - msc in pmf patients will help to characterize their molecular alterations and to understand their involvement in the hematopoietic stem / progenitor cell deregulation that features pmf .

we report a case of ectopic thyroid tissue at base of tongue , another at the level of hyoid , and third one at aberrant tissue suprahyoid location in a 16-year - old female who presented with swelling in front of the neck . pre - operative thyroid scan helped in establishing diagnosis of ectopic thyroid , which was the only functioning thyroid tissue , thus preventing unnecessary surgery [ figure 1 ] . tc 99 m tco4 scan showing triple ectopic thyroid tissue . showing ectopic thyroid tissue at suprahyoid level ( shown by simple arrow ) ectopic thyroid tissue at the level of thyroid ( shown by open arrow ) third ectopic thyroid tissue at the base of tongue ( shown by simple line ) therefore , it is suggested that thyroid scan and thyroid must be done as routine work up pre - operatively to avoid unnecessary surgeries . 16-year - old female presented with an anterior mid - line swelling in front of the neck since childhood . she was investigated and ultrasonography ( usg ) neck was performed , which suggested right paramedian neck mass measuring 26 16 13 mm . patient was injected 5 m ci of tc 99 m pertechnetate and static images were acquired after 10 min . initial static images showed avid tracer uptake at the base of tongue and in clinically palpable nodule at the level of hyoid and another small focus of tracer uptake in mid - line just above the clinically palpable nodule [ figures 24 ] . ct scan images of neck region : open arrow showing homogenously enhancing thyroid tissue in clinically palpable nodule ct scan image of neck region : second ectopic thyroid tissue seen at the level of hyoid ( shown by simple arrow ) ct scan image at the level of tongue : showing third ectopic thyroid enhancing lesion at the base of tongue ( shown by open arrow ) marker images were acquired . lateral images were acquired to localize another focus of tracer uptake , which showed the tracer uptake along the line of descent . patient was asked to drink water and images were acquired to exclude possibility of esophageal tracer uptake . thyroid function test dated : 5/08/10 antibodies : thyroid peroxidase ( tpo ) anti - body : positive 11.4 , ana - anti nuclear ab : n : negative . in this case , thyroid tissue is present in a mid - line position above or at the hyoid bone . hypothyroidism with elevation of thyrotropin secretion is commonly present because of the absence of a normal thyroid gland in most instances . an enlarging mass commonly occurs during infancy , childhood , or later life . often , this mass is mistaken for a thyroglossal duct cyst because it is usually located in the same anatomic position . if it is removed , all thyroid tissue may be ablated , a consequence that has definite physiologic as well as possible medico legal implications . to prevent total thyroid ablation , it is recommended that a thyroid scan examination be performed in all the cases of thyroglossal duct cyst before its removal to be certain that a normal thyroid gland is present .

ectopic thyroid tissue is an uncommon congenital aberration . it is extremely rare to have three ectopic foci at three different sites . the thyroid scan has been used successfully to diagnose ectopic thyroid tissue . we report a case of ectopic thyroid tissue at base of tongue , another at the level of hyoid and third one as aberrant tissue at suprahyoid location in a 16 year old female who presented with swelling in front of neck . this patient was clinically diagnosed as thyroglossal cyst and was being planned for surgery . preoperative thyroid scan helped in establishing diagnosis of ectopic thyroid which was the only functioning thyroid tissue . thus , it prevented unnecessary surgery . therefore it is suggested that thyroid scan and usg / ct scan must be done as routine work up in neck swellings pre operatively to avoid unnecessary surgeries .

vagus nerve stimulation ( vns ) is an effective adjunctive therapy for patients with drug - resistant partial - onset epilepsy . the efficacy of vns has also been demonstrated in treating various types of generalized epilepsies , including genetic generalized epilepsy ( gge ) and lennox gastaut syndrome . here , we report that a patient became seizure - free in epilepsia partialis continua ( epc ) with vns therapy combined with antiepileptic drug ( aed ) regimens . a 21-year - old , right - handed man started having seizures at the age of 18 . he reported countless limb shaking for about 10 s and occasional generalized tonic - clonic seizures at a frequency of 57 times per year . his seizures were commonly precipitated by stress , sleep deprivation , aed noncompliance , and changes in emotion , such as excitation and anger . he was also treated with carbamazepine ( cbz ) , which provided better seizure control , but its effectiveness disappeared four months later . then , he was treated with lamotrigine ( ltg ) at 200 mg daily , levetiracetam ( lev ) at 1250 mg daily , and topiramate ( tpm ) at 200 mg daily with minimal benefits for the last several months . his general physical and neurological examinations were normal , and his family history was noncontributory . however , he suffered head trauma at the age of three , and his brain mri revealed that the signal of the cortex in the head of the right putamen disappeared , and the lenticular nucleus was somewhat small , with suspected developmental delay ( fig . 1 ) , and long - term video - eeg monitoring revealed small spike - wave discharges . sometimes , he could not even say a word or have dinner due to mouth twitching , which also prevented him from working . he was referred by his neurologist to our epilepsy center for evaluation for possible vns therapy . the initial stimulation parameters were the following : current output of 0.25 ma , frequency of 30 hz , pulse width of 250 s , 30 s of signal - on time , and 5 min of signal - off time . then , his stimulation current output was changed to 0.50 ma , and his seizures became countless as they were pre - operation . fortunately , he became seizure - free after his stimulation current was reverted to 0.25 ma . after one month of seizure freedom , the patient withdrew from his lev and tpm medications . he has remained seizure - free for almost 9 months , during which time he has been gainfully employed . in this particular patient , a history of aed noncompliance may have falsely created the appearance of drug - resistant seizures . in general , patients with vns rarely achieve seizure freedom . only one of 198 ( 0.5% ) patients became seizure - free in an early randomized active - control trial . in more recent uncontrolled case studies , significantly higher seizure freedom rates in patients with vns have been observed . reported that 6 of 47 ( 13% ) patients became seizure - free , while ghaemi et al . reported that 10 of 144 ( 6.9% ) patients became free from seizures . earlier treatment with vns in the course of a seizure disorder is associated with a greater likelihood of improvement . the patient in this study not only has been seizure - free for 9 months , but was also able to taper off aed treatment vns implantation . we believe that his remission was achieved by vns . just as any electronic medication , the parameter adjustment of vns , like the dosage of medications , is based on patient profiles . it is a double - edged sword in terms of vns efficacy for drug - resistant epilepsy . when the standard parameters used are 0.25 ma , 20 hz , 250 s , 30 s on , and 5 min off , continuously , the patient experienced two prominent twitches of the mouth weekly . when the parameters were changed ( 0.50 ma , 20 hz , 250 s , 30 s on , and 5 min off , continuously ) , his seizures became countless as they were pre - operation . when the parameters were adjusted back to 0.25 ma , 20 hz , 250 s , 30 s on , and 5 min off , continuously , the patient became seizure - free . we believe that it is clinically important to document such cases in the hope of appreciating the clinical features of patients who have the potential to become seizure - free with vns therapy combined with antiepileptic medication regimens , and , for some patients , the chance to withdraw from the use of aeds .

vagus nerve stimulation ( vns ) is generally considered as a palliative treatment for patients with drug - resistant partial - onset epilepsy . we report a case in which a patient with drug - resistant epilepsia partialis continua ( epc ) , became seizure - free for 15 months with vns combined with antiepileptic medication regimens . to our knowledge , similar cases have not been reported previously .

these difficulties include cold welding between the screw head and locking screw hole , stripping of the recess of the screw head for the screwdriver , and cross - threading between threads in the screw head and screw hole . however , there are cases in which removal is difficult . we describe a new technique for removing a round headed , jammed locking screws from a locking plate . 55 years old male patient received a locking distal tibial plate along with distal fibular plate 3years back from uae . now patient came with complaint of non - healing ulcer over medial aspect of lower 1/3rd of right leg from past 1 year . the patient consented to implant removal , with the express understanding that implant removal might be impossible because already one failed attempt had been performed at some other hospital six months back . we used stainless steel metal cutting blades that are used to cut door locks or pad locks to cut the remaining stripped headed screws . this technique is very quick , easy to perform and inexpensive because the metal cutting blades which are used to cut the screws are very cheap . yet it is very effective technique to remove the stripped headed or jammed locking screws . it is also very less destructive because of very less heat production during the procedure there is no problem of thermal necrosis to the bone or the surrounding soft tissue . these difficulties include cold welding between the screw head and locking screw hole , stripping of the recess of the screw head for the screwdriver , and cross - threading between threads in the screw head and screw hole . these include using a conical extraction screw , cutting the plate , and using high - speed carbide drill bits and burrs to remove the screw heads , and removing the shanks with conical extraction screws . the available screw removal kits make implant removal successful more often than not . however , there are cases in which removal is difficult . we describe a new technique for removing a round headed , jammed locking screws from a locking plate . preoperative antero - posterior and lateral view showing locking plate in distal tibia with 5 distal locking screws and 5 proximal locking screws . the 55 years old male patient received a locking distal tibial plate along with distal fibular plate 3years back from uae . now patient came with complaint of non healing ulcer over medial aspect of lower 1/3rd of right leg from past 1 year . the patient consented to implant removal , with the express understanding that implant removal might be impossible because already one failed attempt had been performed at some other hospital six months back . we used the ao synthes screw extraction kit along with conical extraction screw ( ao synthes ) but the screws did not come out . we used stainless steel metal cutting blades that are used to cut door locks or pad locks to cut the remaining stripped headed screws . firstly , after exposing the plate to be removed a space is created between locking plate and bone adjacent to screws to be cut with the help of sharp osteotome . then an iron cutting blade which was previously autoclaved introduced between plate and bone adjacent to screws to be cut and with to and fro motion all the remaining screws were cut . the remaining threaded parts of screws were left in the bone because there removal may further weaken the bone . screws were cut with care with slow to and fro motion of blades but with firm pressure on blade to avoid any unnecessary soft tissue injury . it only takes 10 minutes to cut all the remaining 4 proximal screws and there was no heating problem during the cutting of screws as there is with other procedures such carbide drills and high speed burrs . at the end of the procedure , we name this technique as rohit s technique for removal of stripped headed / jammed interlocking screws . implant removal is considered for pain related to implants , part of treatment , and patient - requested implant removal . risks of implant removal include wound - healing problems , neurovascular injury , failure to remove all of the implant , and refracture . difficulties in removing a titanium locking screw include jammed screws , damage to the recess in the screw head ( stripping ) for the screwdriver , and broken screws . instruments including conical extraction screws , hollow reamers , extraction bolts , modular devices , and carbide drill bits have been described in the methods used for removing locking screws [ 2 , 6 ] . it also is accepted that no one technique can solve all problems in implant removal . we believe failure to remove the distal screws directly with the conical extraction screw was attributable to the following factors : jamming of the screw head in the locking screw hole , owing to cross - threading and not necessarily cold welding ; grip of the screw threads in the far cortex ; bony growth over the titanium screw at the far cortex ; and as the conical extraction screw was inserted , the screw head jammed farther in the screw hole by expanding the screw head . there is always the danger of thermal bone necrosis or iatrogenic bony injury when using high speed burrs and discs . but our technique is less destructive as produces very less heat as compared to any others because it is not mechanical but a manual procedure . intraoperative picture showing remaining threaded part of screws in the bone afte removal of plate along with jammed / stripped heads of screws . post operative picture of removed tibial plate along with jammed screws in plate that are cut along the undersurface of plate . it is essential to have all the appropriate implant removal instruments , including carbide drill bits and high - speed burrs and discs , and prepare for a long procedure . the risks of high - speed burrs and discs are high local temperature and metal debris . this technique requires running normal saline solution and continuous suction to remove all the metal debris . this technique is very quick , easy to perform and inexpensive because the metal cutting blades which are used to cut the screws are very cheap . yet it is very effective technique to remove the stripped headed or jammed locking screws . it is also very less destructive because of very less heat production during the procedure there is no problem of thermal necrosis to the bone or the surrounding soft tissue . inexpensive & effective method for removal of such implants which are extremely difficult as a result of round headed , cold welding and jammed locking screws heads .

introduction : the advent of locking plates has brought new problems in implant removal . difficulty in removing screws from a locking plate is well - known . these difficulties include cold welding between the screw head and locking screw hole , stripping of the recess of the screw head for the screwdriver , and cross - threading between threads in the screw head and screw hole . however , there are cases in which removal is difficult . we describe a new technique for removing a round headed , jammed locking screws from a locking plate.case report:55 years old male patient received a locking distal tibial plate along with distal fibular plate 3years back from uae . now patient came with complaint of non - healing ulcer over medial aspect of lower 1/3rd of right leg from past 1 year . non operative management did not improve the symptoms . the patient consented to implant removal , with the express understanding that implant removal might be impossible because already one failed attempt had been performed at some other hospital six months back . we then decided to proceed with the new technique . the rest of the proximal screws were removed using a technique not previously described . we used stainless steel metal cutting blades that are used to cut door locks or pad locks to cut the remaining stripped headed screws.conclusion:this technique is very quick , easy to perform and inexpensive because the metal cutting blades which are used to cut the screws are very cheap . yet it is very effective technique to remove the stripped headed or jammed locking screws . it is also very less destructive because of very less heat production during the procedure there is no problem of thermal necrosis to the bone or the surrounding soft tissue .

tendinous xanthomas are caused by impairment in lipoprotein regulation , which results in accumulated cholesterol deposits in the tendons , ligaments , or periosteum . the nodules are most often found over the achilles tendons , hands , and the extensor surfaces of the elbows and knees . these slow - growing nodules are firm and mobile and can present with a yellowish hue . as the nodules enlarge , they can cause pain , restricted joint mobility , disability , and tendon rupture . tendinous xanthomas are commonly associated with familial hypercholesterolemia ( fh ) , an autosomal dominant disorder due to a mutation in the ldl receptor gene , which results in impaired cellular uptake of ldl . however , they can rarely be seen in cerebrotendinous xanthomatosis or beta - sitosterolemia , both of which are autosomal recessive disorders . histopathologically , tendinous xanthomas are composed of accumulated foam cells ( enlarged macrophages , resulting from phagocytosis of elevated ldl cholesterol in the plasma ) , histiocytes , and lymphocytes , which infiltrate the tendon or integument . the process is similar to atherosclerotic plaque formation , and demonstrates that xanthomas can be a marker for cardiovascular disease . tendinous xanthomas in association with fh carry a 300% increased risk of cardiovascular disease as well as an increased risk for lymphoproliferative malignancies . however , based on an estimated prevalence of 1/200 , a recent screening study suggests that fh is underdiagnosed as less than 1% of patients with fh are routinely identified . a 43-year - old african - american male presented with a 35-year history of multiple , slowly enlarging , subcutaneous nodules , which restrict his joint motion and are frequently painful . on examination , multiple ivory colored , firm , but mobile nodules overlie the dorsal aspects of the proximal and distal interphalangeal joints and multiple metacarpal phalangeal joints in the hands ( fig . 2c ) , sole of the feet , and the helix , scapha , and anti - helix of the ears ( fig . 3a , b ) . he has had surgical removal of the nodules in the past , but they recur within a few years . laboratory tests were remarkable for a total cholesterol of 518 mg / dl ( 13.4 mmol / l ) . patients who are heterozygous or homozygous for fh will have elevated cholesterol levels from birth . homozygous patients will typically have ldl cholesterol levels over 13 mmol / l in adulthood and 11 mmol / l in childhood . in contrast , heterozygous patients usually demonstrate ldl levels of 7.5 mmol / l or less . patients with homozygous fh manifest advanced atherosclerosis and xanthomas in childhood , often leading to death before the third decade if left untreated . heterozygous patients for fh generally develop xanthomas in the second decade and have an increased likelihood of a cardiac event prior to the fifth decade if left untreated . therefore , tendinous xanthomas can be confused with other growths such as rheumatoid nodules , giant cell tumors of the tendon sheath , ganglions , and sarcomas with xanthomatous changes . in patients with multiple nodules , histologically , tendinous xanthomas differ from giant cell tumors due to a lack of round cells and a paucity of the multinucleated giant cells . sarcoma with xanthomatous changes can be distinguished by careful attention to the presence of atypical mitotic figures , osteoblastic , chondroblastic or fibroblastic extracellular matrix , and pleomorphic and hyperchromatic nuclei on biopsy . the diagnosis of fh with tendinous xanthomas can be made based on examination coupled with an elevated ldl cholesterol , ( frequently above the 75th percentile ) , elevated total cholesterol , arcus senilis , and a family history of premature cardiovascular disease . if achilles tendon enlargement is present , an ultrasound of the tendon often reveals a thickened tendon with echolucent regions . elevated ldl levels lead to the development of both the tendinous xanthomas and atherosclerotic plaques . treatment is focused on decreasing ldl levels through the use of statin medications , or ezetimibe , combined with dietary modification and counseling regarding the risks of alcohol , smoking , and sedentary lifestyle . for more severe cases , combination therapy with a bile acid sequestrant , nicotinic acid , fibrates , low - density lipoprotein apheresis , or orthotopic liver transplantation very large tendinous xanthomas , or those that impede joint function , will typically require surgical removal with possible skin grafting . xanthomas can also appear as a consequence of elevated lipid levels secondary to liver or kidney disease , bile duct obstruction , diabetes , hypothyroidism , or alcoholism . the patient involved in this case report has signed an informed consent allowing the use of pictures and information in an anonymous format . the authors have no conflicts of interest and have not received any funding or financial consideration with respect to this article .

tendinous and subcutaneous xanthomas are nodular deposits of lipid - filled macrophages , which commonly form on the achilles tendon , hands , feet , elbows , and knees . these nodules are frequently associated with familial hyperlipidemia , a group of diseases involving impaired cholesterol metabolism , and the accelerated development of atherosclerotic plaques . since xanthomas may precede the diagnosis of hyperlipidemia , early identification can lead to preventative treatment that reduces the risk and morbidity of cardiovascular disease , including myocardial infarction . this case report presents a 43-year - old african - american male with multiple xanthomas involving the achilles tendon , soles , hands , knees , elbows , and is associated with the unusual involvement of the ear .

incarcerated hernia frequently requires emergency surgery since it is associated with intestinal obstruction and ischemia . however , emergency surgery for intestinal obstruction has a high mortality and morbidity.1,2 recently , we were able to perform elective laparoscopic repair of a morgagni hernia causing obstructive ileus in a very elderly patient by preoperative colonoscopic placement of a transanal decompression tube . the patient was an 88-year - old woman who had experienced vomiting and abdominal distention for three days . plain radiographs showed up an inverted u - shaped pocket of air in the lower mediastinum , and dilated bowel loops ( fig . 1 ) . abdominopelvic ct revealed an incarcerated transverse colonic loop through the diaphragm ( fig . 2 ) . emergency colonoscopy for decompression demonstrated two luminal constriction sites with convergence of mucosal folds at the transverse colon ( fig . 3 ) ; these were consistent with the diaphragmatic indentations of the incarcerated hernia seen by fluoroscopy . we were able to pass the endoscope ( gif - xq240 ; olympus optical co. , tokyo , japan ) through the constrictions with resistance and see the dilated large bowel proximal to the constrictions . however , the endoscope could not be advanced further because of the presence of a walking stick - shaped loop . transanal decompression by inserting an 18 fr levine tube over the guidewire after removing the endoscope failed since the tube could not be advanced beyond the first constriction . accordingly we placed a thinner catheter ( enbd-7-liguory , 7 fr , 250 cm ; cook medical inc . , winston - salem , nc , usa ) , which is designed for nasal biliary drainage , through the working channel of the endoscope beyond the constrictions ( fig . 4 ) . the catheter was irrigated periodically with normal saline to prevent obstruction , and the intestinal contents and gas were drained successfully . follow up abdominal radiograph the next day demonstrated marked regression of the obstructive ileus ( fig . 5 ) and the patient was able to undergo elective laparoscopic repair of the hernia after a week . laparoscopy revealed omental herniation restricted to the anteromedial portion of the left diaphragm , and integrity of the bowel . the omentum was reduced into the abdomen , the hernia sac was excised , and the defect was repaired with a 56 cm mesh patch ( proceed surgical mesh , ethicon inc . , somerville , nj , usa ) . morgagni hernia is a diaphragmatic hernia that accounts for 3% of total intestinal obstructions.3 repair can be performed either by transthoracic or transabdominal approach , and good results with laparoscopic transabdominal repair have been reported recently.3,4 colostomy ( or ileostomy ) , followed by a second operation for its repair , is performed in many cases of colonic obstruction since primary anastomosis is not always feasible.5 however , we were able to safely perform one - step elective laparoscopic repair for the patient with advanced age by endoscopic decompression ; this procedure relieved the symptoms of obstruction , led to medical recovery and a favorable bowel preparation . drainage was successful even though we could place only a thin catheter beyond the constrictions . in fact , catheters of small diameter have the great advantage that they can be positioned through the endoscope . drainage can be effective in spite of the narrow lumen of the catheter if it is prevented from causing obstruction by , for example , periodic irrigation . thus , when it is difficult to position a transanal decompression tube of large diameter by the seldinger technique , insertion of a catheter of smaller diameter through the endoscope can be a useful option . finally , this case suggests that appropriate endoscopic placement of a decompression tube for incarcerated morgagni hernia permits elective and less invasive laparoscopic repair in patients at greater risk from emergency surgery .

plain radiographs of an 88-year - old woman who had experienced vomiting and abdominal distention for 3 days revealed a severely obstructed ileus , and abdominopelvic computed tomography revealed an incarcerated morgagni hernia . the endoscope was passed through the constrictions from the diaphragmatic indentations and a thin catheter was placed for decompression . the obstructive ileus regressed markedly after the procedure ; the patient underwent elective laparoscopic repair of the hernia 1 week later . this is believed to be the first case of endoscopic preoperative decompression for an incarcerated morgagni hernia .

in a study published in this issue of critical care , gogos and colleagues investigated the influence of the type of bacterial infection , the compartment where it occurs , its origin ( community or nosocomial ) , and its severity ( sepsis versus severe sepsis or septic shock ) on lymphopenia , on the respective number of mononuclear cell subsets , on apoptosis of circulating mononuclear cells , and on hla - dr expression on monocytes . the same group had already reported that tumor necrosis factor ( tnf ) and interleukin ( il)-6 production by lipopolysaccharide ( lps)-stimulated monocytes was lower in sepsis patients with ventilator - associated pneumonia than in patients with sepsis due to other types of infections . these analyses permit clinicians to monitor sepsis patients ' immune status , which undergoes numerous modifications gathered under the term ' compensatory anti - inflammatory response syndrome ' . it affects most lymphocyte subsets , although some divergent observations for b lymphocytes exist [ 4 - 6 ] . importantly , lymphopenia is accompanied by modifications of the cd4/cd8ratio and the relative percentage of cellular subsets . for example , among lymphocytes , the percentages of treg ( regulatory t ) and of natural killer ( nk ) cells are enhanced . lymphopenia already has been associated with bacteremia , has been found to be more severe in patients with gram - positive infection than in those with gram - negative infection , and has been found to inversely correlate with outcome . it can be mimicked by injections of live bacteria , lps , il-1 , or tnf in animal models . the mechanisms that lead to lymphopenia are mainly a redistribution of activated cells that leave the blood compartment to migrate toward the tissues , particularly toward lymphatic tissues , and the occurrence of apoptosis . apoptosis of lymphocytes during human sepsis was revealed by the hotchkiss group when studying the spleens of patients who died of sepsis . le tulzo and colleagues showed that apoptosis of circulating lymphocytes was significantly lower in patients with sepsis than in those with septic shock . hotchkiss and colleagues showed that apoptosis was affecting circulating nk cells , b lymphocytes , and cd4and cd8 t lymphocytes . the reduced hla - dr expression on cd14monocytes is another hallmark of sepsis and systemic inflammatory response syndrome . it is a useful prognosis marker of intensive care patients and correlates with the occurrence of sepsis . measurements performed a few days after the onset of sepsis appear as a prognosis marker , and low expression correlates with poor outcome . il-10 and glucocorticoids are the main mediators that lower hla - dr expression , although they act differently on cd14cd16and cd14cd16monocyte subsets . the present study illustrates the importance of being careful when comparing different reports , which often include different types of patients with sepsis . the heterogeneity of the patients gathered under the term ' sepsis ' is a nightmare for anyone who wishes to submit grant applications or articles , since reviewers can easily argue that the studied group is ill defined and too heterogeneous ! this study further emphasizes the difficulty of reaching definite conclusions on patients with sepsis when considered as a global group . the conclusions drawn for sepsis patients with pyelonephritis may not be true for sepsis patients with community - acquired pneumonia or intra - abdominal infection . however , although the authors report differences , these differences were minimal . only community - acquired pneumonia was associated with a higher number of nk cells as compared with the other groups , and only intra - abdominal infection was associated with an enhanced number of cd8cells . the latter group was the only one with a significantly enhanced number of apoptotic cd8cells . reduced expression of hla - dr on cd14cells was seen mainly in patients infected with klebsiella pneumoniae or acinetobacter baumanii . surprisingly , when patients with sepsis were compared with those with severe sepsis and septic shock , the number of significant differences in terms of the number of circulating nk cells , cd4 t lymphocytes , cd8 t lymphocytes , and b lymphocytes was limited to community - acquired pneumonia and intra - abdominal infection . such a difference was not seen in patients with nosocomial pneumonia , pyelonephritis , or bacteremia . enhanced apoptosis of nk and nkt cells finally , hla - dr expression was particularly reduced in patients with severe sepsis or septic shock due to pyelonephritis or intra - abdominal infection . altogether , it is heartening to note that there were fewer differences than similarities between the different sepsis subgroups . who else but hippocrates can offer us a conclusion for this study from greece : ' it is more important to know what sort of person has a disease than to know what sort of disease a person has ' . il : interleukin ; lps : lipopolysaccharide ; nk : natural killer ; tnf : tumor necrosis factor .

studying a large number of patients with sepsis , the hellenic sepsis study group led by evangello giamarellos - bourboulis emphasizes that the nature of the bacterial infection , its origin ( community or nosocomial ) , its site , and its severity exert different pressures on the immune system . their study illustrates the heterogeneity of patients with sepsis and points out that numerous key parameters of severe infection influence immune status .

biological functions of rnas , including translation of genetic information , cellular signal transduction and transcriptional regulation etc . , are determined by their location in cell ( 1,2 ) . a cell is divided into different compartments that are related to different biological processes ( 3 ) . for example , the rna localized in nuclear usually participates in gene expression regulation or mitosis etc ( 4 ) . thus , the cellular role of the rna after synthesis could be inferred from its subcellular localization information . based on this , subcellular localization for rnas plays an important role in studying biological function of rnas . therefore , it is urgent to construct a database of rna subcellular localization to integrate , analyze and predict rna subcellular localization for speeding up rna structural and functional research . to complement with related research in rna subcellular localization , we developed a web - accessible database ( rnalocate , http://www.rna-society.org/rnalocate/ ) , aimed to collect expanding catalog of diverse species rna subcellular localization in multiple biological processes by manually curating the literature . the first release of rnalocate has contained more than 37 700 manually curated rna subcellular localization entries with experimental evidence , involving 65 organisms ( such as homo sapiens , musmusculus and saccharomyces cerevisiae ) , 42 subcellular localizations ( such as cytoplasm , nucleus , endoplasmic reticulum , ribosome ) and 9 rna categories ( such as mrna , mirna , lncrna ) . hence , rnalocate provides a more specific subcellular localization resource in which to efficiently investigate , browse and analyze a particular rna , and even provides insight into the functions of hypothetical or novel rnas . the whole data set can be easily queried and downloaded through the webpage , and visualization tools for interactively browsing and analyzing the data set are provided . in order to collect all available rnas , rnalocate integrates all types of rna symbols , mainly including microrna symbols from the mirbase database ( 5 ) , long non - coding rna ( lncrna ) and mrna symbols from ncbi gene and ensemble genome database ( 6,7 ) . other ncrna category names are also included , such as transfer rna and small nuclear rna from ncbi gene and ensemble genome database ( 6,7 ) . the list of subcellular localization names was collected according to the gene ontology ( go ) ( 8) . we have written a simple script to screen all abstracts and articles in the pubmed database using the following keyword combinations : ( each rna symbol or rna category name ) and/or ( each subcellular localization ) . the relevant hits were further inspected manually . besides , we also retrieved several thousand subcellular localization entries from lncrnadb ( 9 ) , pombase ( 10 ) , flybase ( 11 ) , tair ( 12 ) and dot ( 13 ) databases ( figure 1 ) . it has been tested in the google chrome , firefox and internet explorer web browsers . rna subcellular localization information was manually obtained from articles published in the pubmed database before may 2016 . in current version , rnalocate documents 37 772 rna subcellular localization entries with experimental evidence from 65 organisms , involving 42 subcellular localizations ( figure 2 ) and 9 rna categories ( including csrna , lncrna , mrna , mirna , pirna , snrna , rrna , snorna and trna ) ( figure 3 ) . among these , more than 1400 entries were collected from lncrnadb , pombase , flybase , tair and dot databases . each subcellular localization entry contains detailed information on rna symbol , rna category , alias , organism , sequence , homology , subcellular localization , tissue , validation method , pubmed i d , detailed description and network . the hierarchical organization and statistics of rna subcellular localization . ( a ) the percentage of 9 rna categories in rnalocate database ( b ) the entry number of 65 organism in rnalocate database , only the organisms with 100 entries have been listed , respectively . in submit page , rnalocate invites users to upload novel rna subcellular localization data , and in blast page , sequence alignment can be done after parameter selection . except these , the whole data set could be downloaded through two approaches : basic download and api ( application programming interface ) . in basic download page , the whole data are saved in microsoft excel and txt formats , users can get them by clicking the download button . in statistics ( detailed statistical tables ) , tutorial ( procedure and illustrations of rnalocate ) and sister databases. organism and other i d ( mirbase id / entrez id). rnalocate provides brief details of search results as a table in the search result page , while more detailed descriptions such as pubmed i d and description of the reference are displayed in search result page , the detail page presents more associated information of the rna , such as organism , subcellular localization , alias , sequence , homology and validated method . more than 9200 rnas with orthology / paralogy from mirbase and homologene database have been provided in rnalocate for investigation on rna subcellular localizations conservation . to further understand the interaction information between different rnas in various types of subcellular localizations online , a network option has also been provided to visualize rna interaction network with subcellular localization and organism ( 14,15 ) . in browse page , users can access rnalocate in three different paths : by localization , by rna category and by organism. a treeview and figure have been displayed in the three pages , respectively . users could get browse results by clicking the node on the tree or the associated name in the figure . for convenience , the data in rnalocate are organized using a hierarchical structure of subcellular localization , according to the cellular component annotations documented in go ( 8) . several subcellular localization databases focused on proteins have been previously constructed , such as dbsubloc , organelle db , esldb , locate , suba , locdb and psortdb databases ( 3,1621 ) . however , recent development has indicated that protein subcellular localization are perhaps only half of the story in cells , since an expanding catalog of diverse rnas is actively involved in multiple biological processes in different subcellular localization . to complement with this absence , we developed the rnalocate database by organizing and presenting rna subcellular localization data for 65 organisms across 9 rna categories . to our knowledge , this is the first database comprehensively focusing on rna subcellular localization . we hope this resource will bridge the gap in rnas and subcellular localization research , and stimulate further interesting elucidating the entirety of rna subcellular localization , and developing new prediction methods . in the future

increasing evidence has revealed that rna subcellular localization is a very important feature for deeply understanding rna 's biological functions after being transported into intra- or extra - cellular regions . rnalocate is a web - accessible database that aims to provide a high - quality rna subcellular localization resource and facilitate future researches on rna function or structure . the current version of rnalocate documents more than 37 700 manually curated rna subcellular localization entries with experimental evidence , involving more than 21 800 rnas with 42 subcellular localizations in 65 species , mainly including homo sapiens , mus musculus and saccharomyces cerevisiae etc . besides , rna homology , sequence and interaction data have also been integrated into rnalocate . users can access these data through online search , browse , blast and visualization tools . in conclusion , rnalocate will be of help in elucidating the entirety of rna subcellular localization , and developing new prediction methods . the database is available at http://www.rna - society.org / rnalocate/.

it is estimated that in the united states , approximately 207,000 women were diagnosed with invasive breast cancer and approximately 40,000 women died from the disease in 2010 . between 1999 and 2005 , 48% of women in the united states initially diagnosed with breast cancer were found to have metastatic disease . the most common sites of breast cancer metastases are to bone , liver , brain , lung , and subcutaneous tissues . we report the use of endoscopic ultrasound ( eus ) in establishing the diagnosis of recurrent breast cancer to an intraabdominal lymph node . a 43-year - old female was diagnosed with invasive ductal carcinoma ( modified bloom - richardson grade iii , estrogen receptor negative , progesterone receptor negative , her2/neu negative ) of the left breast in 2008 by needle biopsy . she subsequently completed neoadjuvant therapy with cyclophosphamide , doxorubicin , and fluorouracil followed by an incomplete course of paclitaxel , which was discontinued prematurely due to neuropathy . at the time of left radical mastectomy , a 2.5 cm tumor with 7 out of 30 lymph nodes positive for malignancy was found ( stage iiic ) . adjuvant therapy with radiation and docetaxel computed tomography ( ct ) scans after adjuvant therapy were notable for an enlarging left upper lobe lung nodule concerning for metastatic disease . a subsequent positron emission tomography ( pet ) scan approximately 11 months after surgery demonstrated increased uptake of the pulmonary nodule seen on ct as well as in the right suprarenal region , which were both concerning for metastatic disease . due to the potential morbidity associated with sampling the lung nodule , eus demonstrated an isoechoic , well - defined 2.5 cm lymph node adjacent to the right kidney ( fig . six passes were made with a 22 gauge fine needle aspiration needle under eus guidance . the patient tolerated the procedure well without complications and was discharged home 1 h after the procedure . the final cytologic impression was consistent with metastatic breast cancer with a similar immunohistochemical profile to the primary tumor . however , it has also been utilized for sampling ascites , the adrenal glands , as well as lymph nodes surrounding the esophagus , stomach , proximal duodenum , and rectum to aid in the diagnosis of malignancy [ 2 , 3 , 4 , 5 ] . while eus has previously been shown to be useful in diagnosing metastatic breast cancer to the esophagus , mediastinum , pancreas , stomach , and peritoneum [ 2 , 3 , 4 , 6 , 7 , 8 ] , there have been no reports to our knowledge describing the use of eus for diagnosing an intraabdominal lymph node recurrence of breast cancer as in this case . since the diagnosis of metastatic breast cancer was established by eus , the patient was able to receive adjuvant therapy without undergoing more invasive procedures to sample the concerning pulmonary nodule . in conclusion , the use of eus should be considered as a less invasive modality for diagnosing primary or recurrent malignancies located adjacent to the upper or lower gastrointestinal tract .

breast cancer can present with metastatic disease initially or as a systemic relapse despite seemingly adequate initial treatment . we report a case of suspected metastatic breast cancer to an intraabdominal lymph node based on imaging , which was subsequently confirmed by tissue sampling at the time of endoscopic ultrasound ( eus ) . while previous studies have shown the utility of eus in the diagnosis of metastatic breast cancer , this is the first case to our knowledge that describes the use of eus in diagnosing recurrent breast cancer to an intraabdominal lymph node .

we examined amdv antibody from each of the 2 patients by countercurrent and line electrophoresis ( 13 ) . dna was extracted from lymph nodes ( patient 1 ) and from peripheral blood and bone marrow ( patient 2 ) before amplification with amdv - specific primers . amdv dna was identified by 2 different sets of primers in the standard pcr ( 5600 bp ) and with 2 complete different internal primers in the nested pcr ( 200 bp ) . pcr products were cloned , and some clones were sequenced to confirm the presence of amdv dna . patient 1 was a mink farmer who had been exposed to amdv - infected mink for 10 years . arteriography showed bilateral occlusions of several lower limb arteries and associated development of a collateral network of vessels . at the age of 25 , he underwent embolectomy , and the removed tissue showed vessel wall inflammation with a granulomatous appearance but no necrotizing lesions or epitheloid or eosinophilic infiltration . over the next 10 years , despite surgical attempts to revascularize and treatment with anticoagulant drugs , his condition deteriorated : his renal , mesenteric , and axillary arteries became stenosed , and antibodies to amdv were found in his serum at the end of these 10 years and at 2 subsequent measurements after 1 additional year . an abdominal aortic biopsy showed adventitial lymphoplasmacytic cell infiltration and minimal atherosclerosis ( figure 1 ) . a lymph node biopsy sample showed modest reactive changes and t - zone hyperplasia , and amdv dna was identified in the sample . at 35 years of age , the patient had a positive serologic result for anti - amdv antibodies and severe claudication . subsequent testing 1 and 2 years later showed negative results for amdv antibodies and amdv genome . the patient died in 1999 , at 40 years of age , at which time his clinical condition resembled that of bilateral pneumonia . postmortem examination showed periarterial collagen deposits , adventitial focal mononuclear accumulations , neutrophil infiltration in the media , fibrosis - related hyperplasia , lipid deposition and calcifications of the intima , and microabscesses within intraluminal thrombotic material . histopathologic appearance of abdominal aortic biopsy sample from 35-year - old mink farmer in denmark who had been exposed to aleutian mink disease parvovirusinfected mink for 10 years ( patient 1 ) . he had been exposed to amdv since the age of 20 . at 54 years of age , 2 years after an extensive outbreak of amdv among his mink a renal biopsy sample showed endocapillary and mesangial proliferative glomerulonephritis with abundant focal semilunes ( figure 2 , panel a ) . immunofluorescence showed anti - immunoglobulin m and anti - c3 antibodies localized to the renal capillaries . electron microscopy showed organized fibrillar deposits of stacked microtubules of 20 nm ( figure 2 , panel b ) , consistent with fibrillary glomerulonephritis ( 14 ) , an idiopathic condition characterized by polyclonal immune deposits with restricted gamma isotypes . immunosuppression improved his renal function , and he remained stable while receiving continuous immunosuppressive medication . histopathologic appearance of renal biopsy sample from 54-year - old mink farmer in denmark who had been exposed to aleutian mink disease parvovirusinfected mink for 34 years ( patient 2 ) . b ) electron microscopy showing distinct extracellular deposits of coarse 20-nm fibrils ( microtubular structures ) characterized as immunotactoid glomerulopathy . eight years later , patient 2 was readmitted to the hospital for diarrhea , vomiting , pyrexia , asthenia , and confusion . cerebrospinal fluid contained high levels of protein and pleocytosis , but no specific infectious agent could be isolated from the cerebrospinal fluid or blood . subsequent investigations repeatedly demonstrated anti - amdv antibodies and amdv dna in peripheral blood and bone marrow . serum was still positive for amdv antibodies 2 years later . despite treatment with antimicrobial drugs , the patient further deteriorated and died in 2004 , at age 63 , after an additional year of hospitalization . at postmortem examination , an adenocarcinoma of the right lung had metastasized to the suprarenal glands , liver , and mesenterium . the clinical history , histopathologic features , and molecular findings for the 2 mink farmers exposed to amdv were similar to those described for ad in mink . the combination of clinical and laboratory findings is unique for these patients compared with previous reports . these 2 patients had micro- and macroangiopathic lesions and prolonged persistence of serum antibodies to amdv and amdv dna . on the basis of its early onset , dissemination , and severity , the slight atherosclerosis found in some histopatologic specimens from patient 1 represent a consequence of the pre - existing arteritis rather than a primary condition . buerger disease is unlikely on the basis of cytopathologic and histopathologic findings , and other vasculitic disorders were excluded on the basis of serologic findings . the arteritis was similar to the autoimmune vascular lesions accompanying ad in mink with adventitial lymphocytic infiltration ( 4 ) . the histopathologic findings for patient 2 , in whom the autoimmune glomerulonephritis was diagnosed 8 years before the first measurement of anti - amdv antibodies , resembled the immune complex mediated glomerulonephritis in mink with ad ( 6 ) . for patient 1 , anti - amdv antibodies persisted 4 years from his last exposure to mink , exceeding the longest reported duration of positive amdv response in a human in the absence of virus exposure ( 11 ) . similarly , patient 2 had a long - lasting antibody response , although under potentially persisting exposure . the persistence of anti - amdv antibodies in patient 2 may reflect host - related factors in the modulation of immune response to chronic antigen stimulation . in mink , host - related factors influence their susceptibility to amdv infection and correlate with clinical manifestations from an asymptomatic condition to overt disease . one may speculate whether the overrepresentation of malignant lymphoma in mink farmers could reflect a part of a disease spectrum paralleling monoclonal plasma cell proliferation in mink ( 15 ) . that amdv dna was found only in the first biopsy sample from patient 1 however , it may reflect technical difficulties with dna amplification after paraffin embedding of the specimen or a possible later clearance of the virus from infected tissues . regardless , we have described our clinicopathologic and molecular findings with the goal of raising awareness about the possible role of amdv replication in human disease .

reports of a possible relationship between aleutian mink disease parvovirus ( amdv ) and human infection are rare . however , 2 mink farmers with vascular disease and microangiopathy similar to that in mink with aleutian disease were found to have amdv - specific antibodies and amdv dna . these findings raise the suspicion that amdv may play a role in human disease .

they are also marker of the atherosclerotic burden of the individual especially the descending aorta . the calcific great vessels , on losing the elastic property place a high afterload on the heart accentuating heart failure . management of these calcific aortas is a controversy and revascularisation of the calcific coronary carry high morbidity and mortality . here , we present two cases where there was presence of extensive calcification of descending aorta in first case and another had calcification of ascending aorta and coronary arteries . a 49-year - old male presented in severe congestive heart failure with history of orthopnoea for last two months . echocardiogram showed a dilated left ventricle ( 78 mm ) with severe aortic and mitral regurgitation . ct angiogram showed extensive calcification of the descending aorta from proximal to bifurcation and also aneurysum of the ascending aorta ( sinus of valsalva 58 mm , sinotubular junction 66 mm ) . patient underwent modified bentall 's procedure under moderate hypothermic cardiac arrest using composite graft ( 29 titling disc valve and 30 mm dacron graft ) . mitral valve was addressed with a 30 rigid ring and tricuspid annuloplasty done with 29 mc3 ring . he was elective ventilated for three days with high ionotropic support and was discharged at 15 postoperative day with stable hemodynamics . a 62-year - old male with known diabetic and hypertensive presented with angina on exertion for the last five months . coronary angiogram showed a proximal left anterior descending ( lad ) lesion of 80% , proximal circumflex lesion of 40% , and osteo - proximal 80% lesion of the right coronary . he underwent percutaneous transluminal coronary angioplasty to the right coronary and a coronary artery bypass to lad using left internal mammary artery . ( a ) : chest x - ray showing cardiomegaly and calcification of the descending thoracic and abdominal aorta ; ( b ) : ct abdomen demonstrating the solar eclipse sign ; ( c & d ) : 3d ct reconstruction of the descending aorta showing extensive calcification extending from the proximal to the bifurcation . ascending aortic aneurysm can also be noted . ( a ) : chest x - ray demonstrating calcific ascending aorta and arch of aorta ( white arrow ) ; ( b ) : lateral chest x - ray demonstrating the calcific ascending aorta ( white arrow ) ; ( c & d ) : angiogram with catheter in the arch of aorta demonstrating the calcific innominate artery ( black arrow ) and calcific coronary artery ( black arrow heads ) . a 49-year - old male presented in severe congestive heart failure with history of orthopnoea for last two months . echocardiogram showed a dilated left ventricle ( 78 mm ) with severe aortic and mitral regurgitation . ct angiogram showed extensive calcification of the descending aorta from proximal to bifurcation and also aneurysum of the ascending aorta ( sinus of valsalva 58 mm , sinotubular junction 66 mm ) . patient underwent modified bentall 's procedure under moderate hypothermic cardiac arrest using composite graft ( 29 titling disc valve and 30 mm dacron graft ) . mitral valve was addressed with a 30 rigid ring and tricuspid annuloplasty done with 29 mc3 ring . he was elective ventilated for three days with high ionotropic support and was discharged at 15 postoperative day with stable hemodynamics . a 62-year - old male with known diabetic and hypertensive presented with angina on exertion for the last five months . coronary angiogram showed a proximal left anterior descending ( lad ) lesion of 80% , proximal circumflex lesion of 40% , and osteo - proximal 80% lesion of the right coronary . he underwent percutaneous transluminal coronary angioplasty to the right coronary and a coronary artery bypass to lad using left internal mammary artery . ( a ) : chest x - ray showing cardiomegaly and calcification of the descending thoracic and abdominal aorta ; ( b ) : ct abdomen demonstrating the solar eclipse sign ; ( c & d ) : 3d ct reconstruction of the descending aorta showing extensive calcification extending from the proximal to the bifurcation . ( a ) : chest x - ray demonstrating calcific ascending aorta and arch of aorta ( white arrow ) ; ( b ) : lateral chest x - ray demonstrating the calcific ascending aorta ( white arrow ) ; ( c & d ) : angiogram with catheter in the arch of aorta demonstrating the calcific innominate artery ( black arrow ) and calcific coronary artery ( black arrow heads ) . there are numerous causes which include infection , inflammation , artherosclerosis , hypertension , hyperuricemia , etc . the severity and the extend of calcification indicate the atherosclerotic burden and is an independent predictor of cardiovascular morbidity and mortality . the windkessel effect is lost in case of inelastic artery placing the heart at a higher work load and promoting heart failure independent of the other factor . eisen , et al . has shown in his paper that descending aortic calcification is more dominant in all events and hence it is a better marker of burden of vascular disease . a simple method developed by schousboe , et al . the aac-8 scale assesses the total length of calcification on the anterior and posterior aorta extending from l1 to l4 . to help us understand the relative risk associated with severe acc is 2.4 , which is equivalent to the relative risk of a lady with total cholesterol of 400 mg / dl . the presence of aortic calcification by plain radiograph predicts the risk of a coronary event in future especially more in diabetic population . coronary artery calcification ( cac ) by itself is an independent predicator of cardiovascular events . the presence of severe cac is a independent predictor of major adverse cardiac event at the end of one year after coronary artery bypass grafting .

calcific aorta is a disease of old age and is an independent risk factor for morbidity and mortality . here , we present two patients with calcific aorta at different levels . one with a descending porcelain aorta , and modified bentall 's procedure was done . second is a patient who is having a calcific ascending aorta and coronary artery . coronary artery bypass grafting from left internal mammary artery to left anterior descending was done for the patient . the calcification and its morbidity had been discussed briefly .

a 30-year - old male presented in the emergency department with a history of bilateral blurring of vision of one - day duration . since his systemic hypertension was not well controlled with this drug his physician had switched over to a combination of atenelol 50 mg with chlorthalidone 12.5 mg ( tenoric 50 , ipca pharmaceuticals ) . refraction was done and his visual acuity was improving to 20/20 in both eyes with a spherical correction of -5 diopter sphere ( ds ) . a cycloplegic refraction revealed a value of -3 ds/-0.5 diopter cylinder ( dc ) x 80 in the right eye and -3.75 ds/-1.0 dc x 130 in the left eye . b - scan ultrasonography showed shallow peripheral serous choroidal detachment [ fig . 2 ] . an optical coherence tomogram ( oct - stratus version 4.0 , zeiss ophthalmics ) was also done since retinal striae were present , which showed a mild thickening of the macula . hematological evaluation including renal parameters and computerized tomogram of the head were within normal limits . he was reviewed after five days and his visual acuity had improved to 20/20 without any refractive error . fundus examination revealed disappearance of retinal striae at the macula and peripheral choroidal effusion had also resolved [ figs . a change analysis was done using the software in stratus oct version 4.0 which revealed definite reduction in the thickness of the macula . we report a case of acute myopia induced by oral consumption of chlorthalidone for systemic hypertension . acute transient myopia may be induced by several drugs and different mechanisms have been described . the exact mechanism producing acute myopia is not very clear even though it has been postulated to be due to ciliary body effusion,1 peripheral uveal effusion2 and ciliary spasm3 and lens swelling . oral sulphonamides cause transient myopia as a result of forward displacement of the lens due to allergic ciliary body edema and rotation.3,4 intravenous administration of equine anti lymphocytic globulins causes transient myopia due to ciliary spasm.7 some of the other drugs that have been described to cause transient myopia include indapamide,5 hydrochlorothiazide,2 triamterene2 and topiramate.8,9 in this case a combination of ciliary spasm and peripheral choroidal effusion explain the induced myopia . since the cycloplegic refraction showed a decrease in myopic shift by about 2 diopter it is evident that there was an element of ciliary spasm . retinal striae have been reported to occur with acute myopia after drug intake.10 ciliary body rotation and edema resulting in forward movement of iris lens diaphragm has been reported as a possible cause for induced myopia by some authors.1,2,3,11 in this case there was no definite shallowing of the anterior chamber . we feel that this mechanism may not explain the pathogenesis of myopia in this case . to our knowledge since this is a common diuretic used in the treatment of systemic hypertension , we feel that it is important to be aware of this possible idiosyncratic adverse effect .

we report a case of sudden loss of vision due to the development of acute myopia after the intake of chlorthalidone used for treating systemic hypertension . clinically this was associated with ciliary spasm , shallow peripheral choroidal effusion and retinal striae at the macula with increase in macular thickness seen on optical coherence tomography . all these findings were reversed completely once the drug was discontinued . development of acute myopia should be kept in mind as an adverse effect of a commonly used antihypertensive drug , namely chlorthalidone .

subaortic membrane is a fibrous membrane below the aortic valve that may involve the ventricular septum , the anterior leaflet of the mitral valve , and the aortic valve itself . sinus of valsalva is a localized bulging in the aortic root opposite to the cusps of the aortic valve . aneurysm of the sinus is a rare condition which may be a congenital or acquired cardiac anomaly , having an incidence of 1.09% in the oriental population and 0.2% in the western population . the unruptured aneurysm is usually silent and often remains undiagnosed , but may cause symptoms by right ventricular outflow obstruction . the rupture may occur into any cardiac chamber , predominantly the right ventricle , the intraventricular septum , and the pericardial space . the pathology of this condition is thought to be due to a failure of the fusion between the aortic media and the heart at the level of annulus fibrosus of the aortic valve , with subsequent aneurysmal enlargement at this weak point due to the high pressure at the root of the aorta . aneurysms of the sinus of valsalva are usually not clinically apparent unless perforation occurs which simulates aortic regurgitation . subaortic membrane usually presents with subvalvular aortic stenosis , left ventricular hypertrophy due to pressure overload , myocardial ischemia , heart failure , and sudden death . a case of infective endocarditis resulting in rsov has been reported in the literature . here , the authors for the first time report an unusual presence of both rsov and subaortic membrane , and the patient presented with thromboembolic complication resulting from infective endocarditis . a 20-year - old male was admitted to the emergency department with complaints of fever for 15 days , increased breathlessness for 2 days and sudden onset weakness of the right side of body since 1 day . past history revealed complaints of breathlessness since the age of 2 years for which he was not investigated . on clinical examination , the patient was febrile ; his pulse was 80/minute , regular , and the blood pressure was 110/70 mmhg . cardiac apex was shifted to left 6 intercostal space lateral to midclavicular line and was hyperdynamic . auscultation revealed continuous murmur of grade iii , best heard at left sternal border and also heard all over the precordium . on chest auscultation , neurological examination showed complete hemiparesis of right side of the body with 3/5 power in the upper extremity and 2/5 power ( mrc scale ) in the lower extremity . laboratory investigations showed the following results : hemoglobin 9.1 gm% ; total leukocyte count 16,870/mm with 70% neutrophils and 25% lymphocytes ; platelet count 1.08 10/mm ; serum blood sugar and electrolytes were normal ; serum urea 65 mg / dl and creatinine 1.5 mg / dl . three sets of blood culture including anaerobic culture were drawn 1 hour apart and they revealed no organism growth after an incubation period of 7 days . 2d echocardiography revealed subaortic membrane causing severe obstruction of left ventricular outflow tract ( lvot ) [ figure 1a ] with rsov into right ventricle , with vegetations seen over mitral and aortic valves [ figure 1b ] . magnetic resonance imaging ( mri ) brain showed acute infarct with hemorrhagic transformation in the left parietal region , with subarachnoid bleed with mass effect . the patient was started on empirical regimen of intravenous antibiotics [ figure 2a and b ] . frusemide ( 60 mg/24 hours ) and nitroglycerine ( started at 10 g / minute ) were given for the initial 2 days and the dose was adjusted with monitoring of blood pressure . he was advised corrective surgery , but due to lack of finances the patient could not be operated . on the third day of treatment , the patient developed cardiogenic shock for which ionotropes were started . ( a ) 2d echo plax view showing subaortic membrane with marked left ventricular hypertrophy and mild pericardial effusion ; ( b ) 2d echo plax view showing vegetation on anterior mitral leaflet , measuring 10 6 mm mri brain axial section showing hypointense signal intensity alteration on t1wi ( a ) and hyperintense on t2 flair ( b ) in left parietal region , suggestive of acute infarct . ventricular septal defect ( in about 50% of cases ) , pulmonary stenosis , tetralogy of fallot , coarctation of aorta , bicuspid aortic valve , valvular and supravalvular aortic stenosis , left superior vena cava and even one case of anomalous origin of left coronary artery from pulmonary artery have been reported to be associated with rsov . the resultant effects are essentially the same as valvular aortic stenosis : left ventricular hypertrophy from the pressure overload , myocardial ischemia , heart failure , and sudden death . in addition , a subaortic membrane may cause aortic insufficiency and permanent structural damage to the aortic valve due to alteration of left ventricular outflow dynamics . our patient fulfilled one major criterion , i.e. there was endocardial involvement by 2d echocardiogram which showed mobile oscillating intracardiac mass on mitral and aortic valves , suggestive of vegetations . also , he fulfilled three minor criteria , i.e. presence of predisposing heart condition in the form of subaortic membrane , fever ( > 100.4f ) and complication in the form of vascular phenomenon . therefore , according to modified duke 's criteria , the patient was diagnosed to have definitive infective endocarditis since he fulfilled one major and three minor criteria . in our patient the patient was advised to undergo valve replacement surgery along with repair of rsov and excision of subaortic membrane . although the valve replacement surgery was advised , due to financial constraints , he was not able to undergo surgery . this problem is faced by many patients in india , since most of them are not under health insurance coverage . on searching google , cochrane , embase and pubmed , it was found that the presence of rsov with subaortic membrane has not been documented till now . infective endocarditis is a rare complication of rsov and along with subaortic membrane makes this case the rarest one .

rupture of the sinus of valsalva ( rsov ) is an uncommonly encountered condition . it can present with wider manifestations ranging from an asymptomatic murmur to cardiogenic shock . the case discussed in this report also had subaortic membrane which usually presents with subvalvular aortic stenosis , left ventricular hypertrophy , myocardial ischemia and sudden death . corrective cardiac surgery was advised , but due to financial constraints , the patient could not be operated and he died . here , the authors report for the first time an unusual presence of both rsov and subaortic membrane and the patient presented with thromboembolic complication resulting from infective endocarditis .

nephrogenic systemic fibrosis ( nsf ) is a debilitating disorder characterized by oedema , plaques , discoloration and severe thickening of the skin resulting in contractures and immobility . currently , exposure to gadolinium - based contrast agents ( gbca ) during low glomerular filtration rate ( gfr ) states appears to be the most consistent risk factor . since gbca is excreted by the kidney , exposure is prolonged in patients with renal insufficiency . the extended exposure permits transmetallation to occur which allows free gadolinium to come in contact with proteins and other cellular components . at the present time , the downstream effects leading to nsf are still not well understood . since gadolinium exists in a trivalent state , we hypothesize that deferoxamine may chelate gadolinium . the patient had chronic glomerulonephritis for many years and was started on dialysis in february 2003 . in october 2005 , she developed a fungal peritonitis secondary to microperforation from colonoscopy . a mr angiogram was performed with 20 cc of a gbca ( estimated 0.13 mmol / kg ) . details of the specific agent were unavailable from her outside records . within a month , the patient began to notice hardening of her legs and hips making walking extremely difficult . the patient underwent uva-1 phototherapy that seemed to slow the progression of her disease but did not improve it . in august 2007 , she received a living - related donor kidney transplantation from her sister . despite excellent renal allograft function ( scr = 0.9 mg/ dl and gfr = 65 ml / min/1.73 m ) , her skin symptoms continued to progress . the patient was experiencing more pain and was having increasing difficulty walking due to contractures in her legs . deferoxamine 500 mg intramuscularly was given daily ( except during the weekend ) for seven doses . after a weekend break where no adverse events were noted , the dose was increased to 1000 mg / day for five additional doses . baseline serum and urine samples were collected along with samples during the two treatment periods . gadolinium was quantified by inductively coupled plasma mass spectrometry ( perkin - elmer life and analytical sciences , shelton , co , usa ) . aqueous acidic calibrating standards and patient samples were diluted with an aqueous acidic diluent ( 1% nitric acid ) containing two internal standards ( terbium and rhodium ) , with terbium used as an internal standard for quantification . serum and urine specimens were analysed in duplicate at a 1:25 dilution ; negative serum , spiked quality control specimens , and patient samples were diluted in an identical manner . serum gadolinium concentrations did not change significantly with deferoxamine treatment ; however , urinary excretion rate doubled after deferoxamine ( table 1 ) . gadolinium clearance was increased from 25 ml / min ( baseline ) to 51 and 67 ml / min with 500 mg / day and 1000 mg / day of deferoxamine , respectively . ferritin was 534 g / l at baseline , 483 g / l at the end of treatment and returned to 532 g / l 1 week after last treatment without iron supplementation . subjectively , the patient felt that her symptoms had stabilized but no substantial improvement was noted 6 months after deferoxamine treatment . her most recent serum gadolinium level was 1.6 ng / ml and urine excretion had returned to baseline at 6.5 g / day after discontinuation of deferoxamine . serum and urine concentrations at baseline and during treatment with deferoxamine ( dfo ) clearances were calculated using the uv / p method . no standard treatment currently exists as no clinical trial has been conducted for the treatment of nsf . most would agree that physical therapy should be a part of any treatment programme , and steroids ( topical or systemic ) are ineffective . these include phototherapy ( uva-1 , psoralen plus uva-1 , photopheresis ) , sodium thiosulfate , plasmapheresis , sirolimus , calcipotriene and cyclophosphamide [ 58 ] . the third category involves therapies that have been confirmed but not refuted . the only medication in this category so far is imatinib , a specific inhibitor of bcr / abl tyrosine kinase that is approved for treatment of chronic myelogenous leukaemia . activity against systemic sclerosis , a separate chronic fibrotic disease of unknown etiology , in an animal model makes imatinib a promising therapy . despite the promising results , one possibility is that the fibrotic reaction can recur as long as a critical amount of gadolinium remains in the tissue . this explains the reports of spontaneous improvement in nsf after recovery of renal function especially in cases of acute renal failure where the exposure is limited . this may also account for some of the differences in responses reported with some of the therapies . the results of our study showed that deferoxamine is capable of chelating and increasing the renal clearance of gadolinium by more than twofold . a dose - dependent relationship was also suggested , but unfortunately not enough data were available to perform a statistical analysis . despite our positive results , deferoxamine is unlikely to be clinically useful because its chelation of gadolinium is too weak . studies with dimeglumine gadopentetate ( gd - dtpa ) showed that patients with a creatinine clearance < 20 ml / min only eliminated 63% of the gadolinium - contrast load . the rest ( 37% ) is retained for an extended period of time . assuming the usual dose ( 0.10.2 mmol / kg ) of gadolinium for mri studies , a 70 kg person would receive between 1 and 2 g of gadolinium . patients with low renal function would retain 370740 mg of gadolinium . at a maximum dose of deferoxamine ( 1000 mg / day ) and an excretion rate of 13 g / day on the other hand , our case demonstrates that it is possible to increase the excretion rate of gadolinium with chelation . if a stronger chelator can be identified , a more rapid removal of gadolinium is achievable . a more timely and effective removal of gadolinium could prove useful in the treatment of this devastating disease .

a 65-year - old female with biopsy - confirmed nephrogenic systemic fibrosis ( nsf ) received a kidney transplantation . despite good kidney function , her symptoms continued to progress . deferoxamine was administered intramuscularly at 500 mg / day and later 1000 mg / day after 1 week with no adverse effects . urine excretion of gadolinium increased from 6.0 g / day to 11.6 g / day and subsequently to 13.0 g / day with 500 mg / day and 1000 mg / day of deferoxamine , respectively . serum levels , however , remain unchanged from 1.7 ng / ml to 1.4 ng / ml . although chelation therapy may have a role in the treatment of nsf , deferoxamine is too weak and a stronger chelator is needed .

recently , it has been shown that olfactory disorders occur at a higher rate than previously thought . the most common etiologies of olfactory dysfunction are sinonasal diseases , head trauma , and upper respiratory infection . other causes include congenital olfactory dysfunction , exposure to toxin , and surgical intervention . among surgical procedures , uvulopalatopharyngoplasty ( uppp ) was introduced as a surgical method for treating obstructive sleep apnea syndrome ( osas ) in the early 1980s . since then , it has become a popular surgical procedure for the treatment of osas and snoring . the most common late side effects after uppp are difficulty in swallowing , nasal regurgitation , pharyngeal dryness , and voice changes . other reported side effects included taste and smell disturbances and velopharyngeal insufficiency . olfactory loss after uppp was reported in two studies , but neither study included olfactory test results [ 6 , 8 ] . herein , we report two patients who complained of olfactory loss after uppp . their olfactory function was measured by widely used olfactory tests and reevaluated after medical treatment . he complained of loss of smell shortly after undergoing uppp for treatment of osas in june 2011 . he had no history of head trauma or any upper respiratory infection before loss of smell but did have mild nasal obstruction . the physical examination showed that the oropharynx was widely open after uppp without any complication . the nasal endoscopy showed that the nasal structures were normal without any nasal secretion in the nasal cavity . on the first visit at our clinic , he received the phenyl ethyl alcohol ( pea ) odor detection threshold test , and his olfactory threshold was 1 . the volume of the right olfactory bulb was 24.25 mm and that of the left olfactory bulb was 25.57 mm . a course of high - dose prednisolone ( 1 mg / kg per day ) with tapering for 2 weeks was given . two months later , the patient found that he could detect some odorants but all of them smelled the same . the score of the traditional chinese version of university of pennsylvania smell identification test ( upsit ) was 16 . two months later , the patient said that his olfactory function improved a little more and his pea odor detection threshold improved to 6.25 , but the score of the traditional chinese version of upsit was 15 . he complained of loss of smell shortly after undergoing uppp for treatment of osas in october 2013 . he had no history of head trauma , upper respiratory infection before loss of smell , or any nasal symptom . the operator saw him several times but nothing was given to treat his smell problem . the nasal endoscopy showed that the nasal structures were normal without any nasal secretion in the nasal cavity . he received the pea odor detection threshold test , and his olfactory threshold was 1 . the volume of the right olfactory bulb was 34.44 mm and that of the left olfactory bulb was 35.93 mm . a course of high - dose prednisolone ( 1 mg / kg per day ) with tapering for 2 weeks was given . the patient was treated with zinc gluconate ( 10 mg t.i.d . ) for a month , and he found that his olfactory function was improved . his pea odor detection threshold was 3.875 , and the score of the traditional chinese version of upsit was 24 . the patient was treated with zinc gluconate for two more months , and his pea odor detection threshold improved to 6.25 . detection threshold tests are used to estimate the lowest concentration of a stimulus that can be detected . in the traditional pea odor detection threshold test , a two - alternative forced - choice single - staircase detection threshold procedure is used . one contains 20 ml of a given concentration of pea dissolved in light mineral oil , whereas the other contains the mineral oil alone . these two bottles are opened and positioned over the subject 's nose in a random order . the geometric mean of the last four reversed points of the seven reversals is used as the threshold estimate . pea concentrations range from 10 to 10 log vol / vol in half - log concentration steps . the normal detection olfactory function ( normosmia ) is defined as pea detection threshold equal to or below 6 , partial loss of detection olfactory function ( hyposmia ) is defined as pea detection threshold higher than 6 but below 1 , and total loss of detection olfactory function ( anosmia ) is defined as pea detection threshold equal to 1 . because of its wide applicability , the upsit has been translated into multiple language versions , including traditional chinese version . the upsit and the traditional chinese version of upsit ( sensonics , inc . , haddon heights , nj ) are comprised of four 10-odorant booklets that can be self - administered in 10 to 15 minutes . odorants is embedded in 10 to 50 m microcapsules fixed in a propriety binder and positioned on brown strips located at the bottom of the pages of each test booklet . when the examinee takes the upsit or traditional chinese version of upsit , he / she releases each of the 40 odorants by scratching the strip with a pencil tip in a standardized manner . the identity of the released odorant is signified by choosing a name from a set of 4 odor descriptors . a response is required for each test item even if no smell is perceived ( i.e. , the test is forced choice ) , allowing for the detection of malingering on the basis of improbable responses . olfactory dysfunction can be classified into two main types : conductive olfactory loss and sensorineural loss . uppp improved nasal breathing in many osas patients with impaired nasal breathing , so the olfactory function in osas patients might be improved by uppp [ 13 , 14 ] . the only large series that evaluated smell disturbances after uppp was conducted by hagert et al . . results of a questionnaire revealed that 22 of 292 patients felt that their olfactory function was impaired 28 years after uppp . they considered that olfactory loss after uppp seemed hard to explain by air flow changes only . it might change air flow through choanae and impair olfactory function , but nasopharyngeal stenosis was not observed in both of our cases by nasal endoscopy . after prednisolone and zinc treatment , their olfactory function improved progressively , as shown by the results of the pea detection threshold test . if olfactory loss is conductive type , systemic steroid therapy usually has a good effect on both detection and identification ability [ 16 , 17 ] . in conclusion , the risk of olfactory loss should be discussed with patients who are going to undergo uppp .

uvulopalatopharyngoplasty ( uppp ) has been a popular surgical method for treating obstructive sleep apnea syndrome since it was introduced in the early 1980s . olfactory loss has been reported as a rare side effect in several cases . however , the olfactory test results and the prognosis were not mentioned in these cases . we present two patients who complained of loss of olfactory function after uppp . their olfactory function was evaluated by the phenyl ethyl alcohol odor detection threshold test and the university of pennsylvania smell identification test . after treatment with steroid and zinc salt , their olfactory function was improved but not recovered completely .

pruritus is a common symptom that has multifactorial etiologies that range from skin to neural and systemic diseases , and its pathophysiology has been , until recently , poorly understood . epidemiological studies have shown that it is common in 8 - 12% of the general population . chronic pruritus has a profound impact on quality of life by disturbing sleep and affecting attention . a large study has shown that hemodialysis patients who itch have a higher mortality risk , which is related to their lack of sleep . a specific separate pathway for histamine - induced itch was found more than a decade ago in a subset of c nerve fibers in humans and later in spinal projection neurons of cats . in 2007 , investigators discovered a separate parallel itch processing pathway activated by cowhage spicules ( mucuna pruriens ) , which revealed an activation of peripheral nerve fibers in humans as well as specific spinal projection neurons in primates [ 5 - 7 ] . however , these c fiber afferents are not itch - specific since they are also activated by heat stimuli that induce the sensation of pain . the active ingredient in cowhage has been isolated as a cysteine protease ( mucunanin ) that activates proteinase - activated receptor 2 ( par2 ) and par4 in nerve fibers and keratinocytes . par2 receptors and their ligands , serine proteases , have previously been demonstrated to have a significant role in the itch associated with atopic eczema . recently , cathepsin s , an endogenous cysteine protease secreted by keratinocytes , was found to induce itch . this finding suggests that cathepsin s may have a role as an itch mediator in inflammatory skin diseases . new evidence for a specific pathway for itch was generated by the findings of neurons expressing a gastrin - releasing peptide receptor ( grpr ) gene that transmit only itch and not pain . grpr is a g protein - coupled receptor for gastrin - releasing peptide ( grp ) , a bombesin - like peptide that is widely distributed in the gastrointestinal tract and central nervous system . moreover , in a model of chronic itch and atopic dermatitis - like skin lesions in mice , the mice pretreated with a grpr antagonist presented no scratching . the role of this receptor in humans and in atopic eczema remains to be defined . the common view is that the epidermis may act as a receptor for itch , but a specific receptor has not yet been clearly identified . recent studies provide evidence that , indeed , there are itch - specific receptors in the skin . a subset of c nerve fibers that contain mrgpra ( mas - related g protein - coupled receptor member a ) , a subfamily of g protein - coupled receptors , were found to mediate itch sensation induced by chloroquine . chloroquine is an antimalarial drug that is known to induce itch in humans , especially in those with dark skin color ( africans ) . these neurons did respond to histamine and capsaicin ( these cells had also expressed grp , the ligand for grpr ) as well as to histamine , providing evidence that these cells play an important role in pruritus . another recent discovery of a possible itch receptor in humans was found in lichen amyloidosis , a localized form of severe itch common in asians and hispanics . a mutation in the oncostatin m receptor ( osmr ) gene , which encodes osmr - beta , an interleukin-31 ( il-31 ) cytokine receptor , was found in these patients . il-31 ( a th2 cell - derived cytokine ) was previously found to elicit itch in atopic dermatitis and prurigo nodularis . an il-31 antibody effectively reduced scratching behavior in an atopic dermatitis - like murine model , suggesting the potential therapeutic role of il-31 antibody in the treatment of chronic itch . the concept of pruritic mediators that act centrally and peripherally is becoming more widely recognized . among the long list of mediators , opioids have a major role in generalized pruritus . it has been known for decades that analgesia obtained with mu opioids induces itch , most probably via reduction of inhibition of pain fibers , whereas mu antagonists , such as naltrexone , inhibit itch . it has been suggested that chronic itch is associated with an imbalance between mu and kappa opioid systems . this effect is not limited to the central nervous system but also occurs in the skin as demonstrated in keratinocytes of patients with atopic eczema . recent results of a phase iii , double - blind study in chronic kidney disease - associated pruritus showed that orally taken nalfurafine effectively reduced itch . of note , nalfurafine was officially approved for clinical use as an antipruritic for chronic kidney disease - associated pruritus in japan last year . chronic pruritus shares many similarities , including peripheral and central sensitization , with chronic pain . therefore , many endogenous inflammatory mediators that are involved in chronic pain via sensitization of nociceptive nerve fibers such as prostanoids , serotonin , nerve growth factor , and transient receptor potential vanilloids ( trpvs ) also have a role in chronic pruritus . these observations taken together may suggest that trpv1 is a relay through which capsaicin exerts its antipruritic effect . beneficial effects of capsaicin have been reported in chronic , localized pruritic disorders , particularly those of neuropathic origin . substance p is a neuropeptide widely distributed in peripheral nerve fibers and the central nervous system and is known to intensify itch perception . a recent study in rats demonstrated that the destruction of substance p receptor neurokinin 1-expressing neurons in the spinal dorsal horn significantly attenuated scratching response . these results suggest that substance p and its neurokinin receptor 1 have a role as itch transmitters in the central nervous system . the existence of central nerve sensitization is demonstrated by studies in chronic itch patients who perceive painful stimuli as itching . moreover , robust activation in the brain in areas involved in central sensitization has been noted in chronic itch . this explains the rationale of using neuroleptics and antidepressants in the treatment of chronic pruritus . the exact mechanisms , as well as the magnitude of their beneficial effects , remain largely unclear . it is time to re - think the current itch treatment strategy that mainly includes topical corticosteroids and oral antihistamines that have limited effect in most types of chronic pruritus . at present , clinical management of chronic pruritus should include the use of drugs that reduce neuronal sensitization for pain ( such as gabapentin ) and pregabalin and selective serotonin and neuroepinpherine antidepressants , either as monotherapies or in combination . hopefully , in the future , we will see a wide range of topical and systemic therapies that target the various receptors and neural pathways that mediate itch of different types and lead to improved quality of life for millions of pruritic patients .

chronic pruritus is an emerging health problem with a significant impact on quality of life . recent advances in our understanding of newly discovered pathways and receptors for itch have been made . it is hoped that recent advancements will also drive the development of novel therapies for this often - neglected and bothersome symptom .

chromophobe renal cell carcinoma ( chrcc ) is a unique entity of renal cell carcinoma ( rcc ) . the chrcc is composed of an admixture of two types of tumor cells with a prominent cell membrane in varying proportions . one type is large pale cells and the other type is smaller granular eosinophilic cells . it is sometimes difficult to distinguish chrcc from renal oncocytoma and other rccs with granular cells , cytologically and , also , histologically.[35 ] i present here a case with an imprint cytology of the chrcc , focusing on the correlation with the histological and ultrastructural features . a 69-year - old male presented with abdominal discomfort and he was hospitalized under the clinical impression of acute cholangitis . the renal masses measured 7.7 cm and 5.5 cm in the greatest dimension at the right lower and left upper poles , respectively . the partial nephrectomy specimen revealed a well - circumscribed , homogeneously tan brown solid mass that measured 665.5 cm [ figure 1 ] . macrophotograph showing a well - circumscribed , brown , solid renal mass the imprint cytologic preparation was made . the smears were highly cellular and the tumor cells were arranged in monolayered sheets or as single cells . the tumor cells were polygonal and they had abundant granular eosinophilic cytoplasm , a well - defined cytoplasmic membrane and accentuated cell borders [ figure 2 ] . the cytoplasm exhibited variable granularity with reticulated clearing or vague perinuclear vacuolization [ figure 3 ] . the nuclei were round or ovoid with a smooth to mildly irregular nuclear membrane , and markedly wrinkled nuclei were infrequently seen . microphotograph from the cytology smear showing sheets composed of polygonal tumor cells with abundant granular cytoplasm , round nuclei and well - defined cytoplasmic membrane ( papanicolaou , 400 ) microphotograph from the cytology smear showing eosinophilic granular cells with reticulated cytoplasmic clearing , vague perinuclear vacuolization ( arrows ) and mutinucleation ( h and e , 400 ) histologically , the tumor consisted of predominantly eosinophilic granular cells arranged in a solid or nested pattern . the tumor cells had round , often binucleated nuclei with a small nucleolus . on higher magnification , immunohistochemically , the tumor cells were diffusely positive for pancytokeratin and cytokeratin 7 and focally positive for cd10 but negative for vimentin and epithelial membrane antigen . microphotograph of histology showing solid growth of eosinophilic granular cells with reticulated cytoplasmic vacuolization and accentuated cell borders ( h and e , 400 ) on electron microscopy , the tumor cells had round to oval nuclei with smooth to focally irregular nuclear membrane and occasional small nucleoli . the cytoplasm was packed diffusely with numerous microvesicles admixed with a considerable amount of mitochondria and intermediate filaments [ figure 5 ] . some tumor cells exhibited globular aggregates of microvesicles that seemed to push their nucleus [ figure 6 ] . electron microphotograph showing numerous microvesicles , scattered mitochondria and complexly plicated plasma membrane ( arrows ) ( 6000 ) electron microphotograph showing a globular aggregate of microvesicles ( arrows ) pushing the nucleus ( 3500 ) right - sided partial nephrectomy was performed 3 months later . macroscopically , the tumor was golden yellow and histologically , it was diagnosed as clear cell rcc . ultrastructurally , chrcc contains numerous microvesicles , which account for the diffuse and strong reaction with hal 's colloidal iron stain . . the cytoplasm exhibits either a pale , finely reticular and almost transparent appearance or a granular eosinophilic appearance . cytomorphologically , the distinct perinuclear halo and wrinkled nuclei are important diagnostic clues . the perinuclear halos of chrcc reflect numerous cytoplasmic microvesicles and perinuclear rarefaction and peripheral condensation of mitochondria on electron microscopic examination . in the present case , however , perinuclear halos and wrinkled nuclei were not conspicuous , causing some confusion with renal oncocytoma and other rccs with granular cells . the indistinct perinuclear halo may reflect the lack of peripheral condensation of mitochondria on the electron microscopic examination . in the present case , numerous microvesicles were packed diffusely or aggregated globularly and a considerable amount of mitochondria were scattered randomly without peripheral condensation . this ultrastructural feature may be responsible for the cytomorphology of the reticular cytoplasmic clearing or the vague perinuclear vacuolization that can also be an important diagnostic clue in distinguishing chrcc from other renal tumors . based on the previous reports and the present case , another unique characteristic cytomorphology of chrcc is a thick , well - defined cell membrane , which reflects a complex plication of the cell membrane on electron microscopic examination . cytologically , the main differential consideration of the chrcc includes renal oncocytoma and clear cell rcc with granular cells . however , renal oncocytoma has a monotonous population of cells with uniform nuclei and the cytoplasm of renal oncocytoma has homogeneous granularity without reticulated clearing or vacuolization characterized by that of the chrcc . binucleation and an accentuated cell border are not as prominent in renal oncocytoma as that of chrcc . it is difficult to distinguish between chrcc and clear cell rcc with predominantly granular cells . however , the cytoplasm of clear cell rcc is friable and the cells show indistinct cell borders on the cytologic smear . clear cell rcc is often associated with a dirty , bubbly background with many foamy histiocytes , and this in contrast to the clean background of chrcc . immunohistochemical stains on the cytologic smear or cell block can be used for making the differential diagnosis . chrcc has a low malignant potential and the treatment of chrcc is usually simple nephrectomy or partial nephrectomy . it is sometimes important to distinguish chrcc from renal oncocytoma on the pre- or intra - operative cytologic smear . particularly , if bilateral renal masses are present , like was present in our patient , or the contralateral kidney is non - functional or absent , then a minimal operation is essential to preserve the renal function .

chromophobe renal cell carcinoma ( chrcc ) is a unique entity of renal cell carcinoma and has a low malignant potential . a correct cytological diagnosis can help to decide the suitable management and operation . i present here a case with an imprint cytology of chrcc focusing on the correlation with the histological and ultrastructural features . a 69-year - old male underwent partial nephrectomy and imprint cytology . the cellular smear consisted of predominantly granular eosinophilic cells with round nuclei , a well - defined cytoplasmic membrane and accentuated cell borders . the cytoplasm was characterized by variable granularity with reticulated clearing or vague perinuclear vacuolization . distinct perinuclear halos were infrequently noted . the histological , immunohistochemical and ultrastructural findings were compatible with chrcc .

hematohidrosis is known to be precipitated by stress , strain , or any sort of exertion , and it may occur in individuals with underlying bleeding disorders . it may occur in individuals suffering from extreme levels of stress . around the sweat glands , there are multiple blood vessels in a net - like form , which constrict under the pressure of great stress . then , as the anxiety passes , the blood vessels dilate to the point of rupture and goes into the sweat glands . as the sweat glands produce a lot of sweat , they push the blood to the surface , which comes out as droplets of blood mixed with sweat . we hereby report a case where bloody sweat discharged from the forehead , face , and body episodically in a healthy young girl who did not have any underlying disorders . a 12-year - old girl visited us with a history of bleeding from the intact skin over the forehead , scalp , cheek , nose , and trunk [ figures 1 and 2 ] for the last 2 years . the bleeding occurred in episodes , once or twice a day , sometimes more frequently , especially on waking up in the morning . no preceding history of stress or anxiety and no preceding episode of tingling sensation were found . each episode started with mild watery secretion over the forehead or other body parts , followed immediately with bright - red colored secretion . each episode lasted for about 10 - 15 min , and the patient remained perfectly alright during the post - episode period until the next episode . no history of ingestion of any anticoagulants , dyes , or other drugs was obtained from her . she did not have any history of major medical or surgical illness in the past . sweat admixed with blood from the right side of the face sweat admixed with blood from nose her general physical examination and systemic examinations did not reveal any abnormality . the skin over the forehead was normal . on gross examination , the secretion was bright - red in color , less viscous than blood , and it was not frank blood . on collection of the secretion and examination of its smeared preparation under a microscope , plenty of erythrocytes were observed ; the sample was benzidine test positive [ figure 3 ] and alkaptonuria negative . her routine hemogram , blood counts , platelet count , bleeding time ( 2 min ) , clotting time ( 3 min 30 sec ) , active partial thrombin time ( 25 sec ; normal range 24 - 32 sec ) , prothrombin time , liver function tests , and renal function tests were within normal limits . peripheral smear of the secretion showed multiple red blood cells ( rbcs ) along with numerous gram - positive cocci and bacilli [ figure 4 ] . benzidine test of the secretion , confirming presence of blood peripheral smear of the secretion showing rbcs and numerous cocci and bacilli psychiatric analysis revealed intelligent quotient ( i.q . ) between 60 and 70 and a loss of insight . the patient was given atropine transdermal patch over the involved sites and she noticed gradual improvement in both the severity and frequency of the episodes . we followed the patient for 2 months after stopping the atropine treatment . during this period hematohidrosis also known as hematidrosis , hemidrosis , and hematidrosis is a condition in which capillary blood vessels that feed the sweat glands rupture , causing them to exude blood ; it occurs under conditions of extreme physical or emotional stress . various causative factors have been suggested by holoubek , like component of systemic disease , vicarious menstruation , excessive exertion , psychogenic , psychogenic purpura , and unknown causes . acute fear and intense mental contemplation are the most frequent causes , as reported in six cases in a study . in our case , one hypothesis proposed for etiopathogenesis of hematohidrosis , as suggested by some authors , is that multiple blood vessels present in a net - like form around the sweat gland constrict under pressure of stress . as the anxiety passes out , the blood vessels dilate to the point of rupture . the blood goes into the sweat glands , which push it along with sweat to the surface , presenting as droplets of blood mixed with sweat . severe mental anxiety activates the sympathetic nervous system to invoke stress - fight reaction to such a degree as to cause hemorrhage of the vessels supplying the sweat glands into the ducts of the sweat glands . they concluded that pathological basis for hematohidrosis might be distinctive vasculitis , but direct immunofluorescence study did not reveal any abnormality in our case . biopsy during symptom free period did not reveal any blood - filled vascular spaces , intradermal bleeding or abnormality in hair follicle , sebaceous , or sweat glands . benzidine test is an important tool in diagnosis , where hemoglobin in blood reacts with hydrogen peroxide - liberating oxygen , which then reacts with organic reagent producing a green to blue colored compound . we believe that a further insight in the etiopathogenesis may help develop more comprehensive management protocol of this rare and unusual condition . 1 . in our case , no underlying precipitating factors such as stress , strain , or any bleeding disorder was identified .

hematohidrosis is a very rare condition in which an individual sweats blood . it may occur in an individual who is suffering from extreme levels of stress . various causative factors have been suggested like component of systemic disease , vicarious menstruation , excessive exertion , psychogenic , and unknown causes . fear and intense mental contemplation are the most frequent causes . it may also occur in bleeding disorders . we here report a case where bloody sweat was discharged from the forehead , face , and body episodically in a 12-year - old healthy girl with no bleeding disorder or any other underlying cause . all investigations done were within normal limits , except low intelligent quotient and loss of insight . the patient was given atropine sulphate transdermal patch with marked improvement in severity .

kawasaki disease is generalized systemic vasculitis.1 ) many head and neck symptoms and signs are manifested in kawasaki disease such as bilateral nonexudative conjunctivitis , erythema of the lips , and oral mucosa and cervical lymphadenopathy . but parotitis is a very uncommon manifestation of kawasaki disease , even though pathologic findings of the parotid gland were described in an autopsy case.2 ) here we report a case of kawasaki disease that presented as parotitis in a 3-month - old infant . a male infant aged 3 months and 1 week , was referred to us after presenting with a 3-day history of high fever and a left cheek mass . at the time of admission , body temperature was 38.7 - 39.7 , heart rate was 140 - 150/min , respiration rate was 32 - 35/min . the patient looked very ill and irritable . from the posterior area of the left ear to the inferior area of the jaw , a hard mass measuring 34 cm was palpated , with a febrile sensation and a flare around the mass . laboratory findings were as follows : hemoglobin 9.7 g / dl , hematocrit 27% , leukocytes 11,820/mm ( 76.5% neutrophils , 13.4% lymphocytes , 6.4% monocytes , 0.9% eosinophils ) , platelets 266,000/mm , c - reactive protein 82.7 mg / l . the patient 's mumps immunoglobulin g ( igg ) and immunoglobulin m ( igm ) measured by enzyme linked immunosorbent assay ( elisa , denka seiken co. , ltd . , however , his mother 's igg and igm were positive , and rheumatoid factor , anti - ro / ssa and anti - la / ssb antibodies were all negative . the finding of a computed tomography ( ct ) scan of his pharynx showed increased intensity in the left parotid gland and the adjacent lymph nodes were enlarged ( fig . 1 ) . therefore , pyogenic parotitis and sepsis were suspected , and antibiotics ( vancomycin , amikacin ) and intravenous immunoglobulin ( ivig , 1 g / day2 days ) were administered on the 1st day of admission . afterward , the swelling in the neck area and skin flares were alleviated slightly , but the high fever persisted . on the 5th day of admission , lip redness and fissure , conjunctival injection , and edema of the hands and feet appeared . at that time , leukocytosis and thrombocytosis were observed ( leukocytes 18,220/mm , platelets 533,000/mm ) , c - reactive protein was 82.2 mg / l , and amylase was 10 thus , kawasaki disease was suspected and ivig ( 2 g / day ) and high - dose aspirin were administered . after 3 weeks , the patient 's mumps igg and igm were converted to positive . echocardiography ( on the 9th day of fever ) results showed diffuse dilatation of the left main coronary artery measuring 2.8 mm ( z score > 3 ) and saccular dilatation of the proximal left anterior descending artery measuring 4.0 mm ( z score > 3 ) ( fig . 2 ) . echocardiography performed at the 1st month after disease onset showed slight regression of the coronary artery ( left main coronary artery 2.8 mm , proximal left anterior descending artery 3.0 mm ) . parotitis has been reported to occur with an increased frequency in young infants born prematurely . staphylococcus aureus has been determined to be the major pathogen cultured from these patients , and the response to antibiotics is good.3)4 ) the case presented here is reported as the second case of parotitis associated with kawasaki disease , but the first case was an adolescent.5 ) in this case , kawasaki disease was not suspected because the patient was too young . the infant we treated was admitted for a mass in the posterior area of the ear with accompanying high fever and pyogenic parotitis and sepsis was suspected . therefore antibiotics and ivig were administered . however , on the 5th day after the administration of antibiotics ( 9th day of fever ) , conjunctival injection and lip redness appeared , and a skin rash began to appear . so , because of unresponsiveness to antibiotics , we suspected that the parotitis was a type of autoimmune disease such as sjgren 's syndrome6 ) with mumps infected by maternal subclinical mumps . although clinical and epidemiological features strongly suggest an infectious cause , efforts to identify an infectious agent in kawasaki disease with conventional bacterial and viral cultures and serological methods have failed to do so.1 ) in this case , however , mumps virus was identified by serologic test and was considered as the etiology of kawasaki disease . although the patient was treated with ivig on admission day because sepsis was suspected , fever did not subside and clinical features of kawasaki disease appeared on the 5th day of admission . over 10% of patients with kawasaki disease failed to respond to initial ivig therapy as our patient shown.7 ) also , there are possible different mechanisms of action of ivig in individuals of very young age , especially below 6 months . a case of unstable angina in an adolescent previously diagnosed with kawasaki disease at the age of 3 month was reported.8 ) hence , long term follow up will be needed in this case because of treatment failure of the initial ivig therapy and the very young age of onset . in conclusion , infants with parotitis that is unresponsive to antibiotics and accompanied by prolonged fever , should be considered kawasaki disease even though typical symptoms are not present .

a male infant aged 3 months and 1 week had persistently high fever with parotitis that was unresponsive to antibiotics . mumps was identified by serologic study , but he was finally diagnosed by clinical features as having kawasaki disease and echocardiographic findings on the 9th day of fever . parotitis , which is unresponsive to antibiotics , should be considered kawasaki disease even though typical symptoms are not present .

gallium-68 ( ga-68 ) dota - peptide positron emission tomography / computer tomography ( pet / ct ) has a higher sensitivity and improved spatial resolution for the detection of somatostatin receptor expressing tumors than conventional somatostatin receptor scintigraphy ( srs ) . anatomical evaluation of therapy response does not correlate well with progression - free survival , clinical outcome , or quality of life in neuroendocrine tumors ( net ) . we present ga-68 dotatate pet / ct findings in a rare case of primary neuroblastoma of the neck and its role in the evaluation of the treatment response . the case we present here is about a 12-year - old female child presented with gradual onset painless neck swelling . contrast enhanced ct study demonstrated large soft - tissue lesions on the left side of the neck , which was later on histopathologically confirmed as neuroblastoma . ga-68 dotatate pet / ct performed for initial staging showed [ figure 1a - c ] abnormal tracer uptake in an enhancing large soft - tissue mass on the left side of neck ( suvmax 11.7 ) , the left cervical and axillary lymph nodes , and bones suggestive of primary neuroblastma in the neck with nodal and skeletal metastases . the patient was treated with three cycles of chemotherapy and ga-68 dotatate pet / ct study was repeated for treatment response evaluation . post - chemotherapy ga-68 dotatate pet / ct showed [ figure 2a - c ] decrease in tracer uptake in the soft - tissue mass in the neck ( suvmax 5.1 in comparison to suvmax 11.7 in the pre - therapy scan ) , in the cervical and axillary lymph nodes , in the paravertebral mass ( suvmax 5.5 in comparison to suvmax 11.0 in the pre - therapy scan ) and in the bones ( suvmax 3.8 in comparison to suvmax 10.0 in the pre - therapy scan ) without significant change in the size of the lesions suggesting favorable response to chemotherapy . f-18 fluoro-2-deoxy - d - glucose ( fdg ) pet / ct was also performed before and after chemotherapy , which confirmed favorable metabolic response , although the decrease in uptake of f-18 fdg was of lesser magnitude than decrease in ga-68 dotatate uptake . pre - therapy gallium-68 ( ga-68 ) dotatate positron emission tomography / computer tomography ( pet / ct ) coronal image ( a ) showing abnormal tracer uptake in an enhancing large soft tissue mass in the left neck ( suvmax 11.7 ) , left cervical and axillary lymph nodes , and multiple bones . transaxial ct ( b ) and fused positron emission tomography / computer tomography ( pet / ct ) ( c ) images show abnormal tracer uptake in a large enhancing softtissue mass on the left side of the neck ( suvmax 11.7 ) post - chemotherapy ga-68 dotatate pet / ct coronal image ( b ) shows decrease in tracer uptake in the soft - tissue mass in the neck ( suvmax 5.1 ) , cervical and axillary lymph nodes and in the skeleton without significant change in the size of the lesions . transaxial ct , ( b ) and fused pet / ct ( c ) images show a significant decrease in tracer avidity ( suvmax 5.1 ) compared with pre - therapy scan the primary tumors most commonly occur within the abdomen ( 65% ) and about half of these tumors arise from the adrenal medulla . other common sites of neuroblastoma include the neck , chest , and pelvis . in general , somatostatin receptors ( particularly subtype 2 ) ga-68-dota - peptide pet / ct has higher sensitivity and improved spatial resolution for the detection of somatostatin receptor positive tumors than conventional srs and is superior to indium-111 octreotide spect in detecting net . ga-68 dota - peptide pet is superior to i-123 mibg imaging and even to the ct or mri technique in pre - therapy staging of neuroblastoma . in this report , we showed ga-68-dotatate pet / ct findings in a patient with primary extra - abdominal neuroblastoma . the peptide receptor radionuclide therapy ( prrnt ) with 177 lu - dotatate is safe and feasible in children with relapsed or primary refractory high - risk neuroblastoma . ga-68 dotatate pet / ct study may further help in the selection of patients for prrnt in such patients with extensive disease . anatomical evaluation of therapy response does not correlate well with progression - free survival , clinical outcome , or quality of life in net . previous study has shown that the decreased ga-68 dotatate uptake in net after chemotherapy can predict clinical improvement . in the current case , ga-68 dotatate pet / ct showed favorable metabolic response to treatment despite significant residual tumor on ct . this interesting case illustrates the utility of ga-68 dotatate pet / ct in the staging and treatment response evaluation in a rare case of primary neuroblastoma of the neck .

gallium-68 ( ga-68 ) dota - peptide positron emission tomography / computer tomography ( pet / ct ) has higher sensitivity and improved spatial resolution for the detection of somatostatin receptor expressing tumors than conventional somatostatin receptor scintigraphy . we present the findings of ga-68 dotatate pet / ct in a rare case of primary neuroblastoma of the neck in a 12-year - old female child and its role in the evaluation of the treatment response .

we collected 109 nasal swab samples from pigs for swine influenza surveillance during november 2011february 2012 . nasal swab samples were collected from healthy pigs , 6 months of age , at an abattoir in gunma prefecture , japan . all cell culture supernatants were tested by using a hemagglutination assay of a 0.7% solution of guinea pig erythrocytes ( 9 ) . to determine the subtype of the isolate , a hemagglutination inhibition assay was performed by using ferret antiserum for a / california/07/2009 [ a(h1n1)pdm09 ] , a / victoria/210/2009 [ a(h3n2 ) ] , b / bangladesh/3333/2007 [ b / yamagata - lineage ] , and b / brisbane/60/2008 [ b / victoria - lineage ] ( 9 ) . one strain of influenza a virus , designated a / swine / gunma/1/2012 , was isolated from the samples . for full genome sequencing of the influenza a / swine / gunma/1/2012 strain , we conducted reverse transcription pcr ( 10 ) . segment - specific primers used for amplification and sequencing are shown in technical appendix figure , panel a. phylogenetic analysis of the nucleotide sequences was conducted by using mega version 5 software ( www.megasoftware.net ) and tree explorer version 2.12 ( http://en.bio-soft.net/tree/treeexplorer.html ) ( 11 ) . the phylogenetic trees of hemagglutinin ( ha ) and neuraminidase ( na ) genes were constructed by using the neighbor - joining method ( 13 ) . in addition , phylogenetic trees based on the matrix protein , nucleoprotein genes , nonstructural protein , polymerase acid , polymerase basic 1 , and polymerase basic 2 were constructed by using the neighbor - joining method . genbank accession numbers assigned to the gene sequences of the analyzed strain are the following : polymerase basic 2 ( ab731582 ) , polymerase basic 1 ( ab731583 ) , polymerase acid ( ab731584 ) , ha ( ab731585 ) , nucleoprotein ( ab731586 ) , na ( ab731587 ) , matrix protein ( ab731588 ) , and nonstructural protein ( ab731589 ) . phylogenetic trees based on ha and na gene sequences are shown in the figure , panels a and b. the identities of the nucleotide sequences of each gene are shown in the table . the a / swine / gunma/1/2012 strain was confirmed as a strain of ph1n1 virus figure , panel a ) . na gene sequences showed that the virus was located within clusters of swine - type viruses documented in japan as the representative strains , such as a / swine / ehime/1/1980 ( figure , panel b ) . the sequence identity of the na gene between the a / swine / gunma/1/2012 strain and other japanese h1n2 siv strains ranged from 85.0 to 97.5% . the identities of other genes between the a / swine / gunma/1/2012 strain and ph1n1 virus vaccine strain ( a / california/07/2009 ) were highly homologous ( > 90% ; table ) . these results suggest that the a / swine / gunma/1/2012 strain was a new reassortant of the h1n2 siv subtype derived from the ph1n1 virus . phylogenetic tree based on the nucleotide sequences of hemagglutinin ( a ) and neuraminidase ( b ) genes of a / swine / gunma/1/2012 , a novel h1n2 swine influenza virus ( siv ) strain . distance was calculated according to the kimura 2-parameter method ; the trees were constructed by using the neighbor - joining method with labeling of the branches showing at least 70% bootstrap support . asterisks indicate reference strains compared with a / swine / gunma/1/2012 used to calculate the identity of neuraminidase gene . pb , polymerase basic ; pa , polymerase acid ; ha , hemagglutinin ; np , nucleoprotein ; mp , matrix protein ; ns , nonstructural protein . the samples ( 109 nasal swabs ) were collected from different pig farms 60 km apart . the epidemiologic association may be low among the samples , because the quarantine inspection system is well established in japan . all samples were collected from pigs 6 months of age ; therefore , the potential for infection with the virus could have been low . additional and larger studies investigating the emergence of the parent virus of the strain may be needed . vijaykrisna et al . found a new reassortant virus among avian - type , swine - type , and ph1n1 viruses ( 6 ) . in addition , monero et al . reported a new reassortant virus between siv , identified in italy , and ph1n1 viruses ( 7 ) . however , to our knowledge , reassortant h1n2 siv strains derived from ph1n1 virus in japan have not been identified before this report . although the transmission of sivs to humans has been reported sporadically , the infectious nature of this reassortant h1n2 strain among humans is unknown . the emergence of a novel h1n2 siv strain raises further concerns about whether the virus will generate further genetic reassortments and gain virulence .

we isolated a novel influenza virus a(h1n2 ) strain from a pig on january 13 , 2012 , in gunma prefecture , japan . phylogenetic analysis showed that the strain was a novel type of double - reassortant virus derived from the swine influenza virus strains h1n1pdm09 and h1n2 , which were prevalent in gunma at that time .

the etiology of folliculitis is complex and in a given case several factors may contribute including infection , physical irritation , occlusion , other skin diseases and drugs . among drugs , however , the role of the native glucocorticoid , cortisol , as a regulator / dampener of potential inflammatory reactions in the hair follicles is unknown . here we report a case of treatment - resistant folliculitis which resolved after recognition and treatment of low cortisol due to adrenal insufficiency . a 40-year - old man was admitted to our clinic with folliculitis which he had suffered from for at least 2 years . besides genital condyloma he had a medical history of psychological problems , tiredness , low libido and lower back pain . as a supplement to body building , he had used anabolic steroids a short period of time more than 15 years before the debut of folliculitis . three years before the debut of folliculitis , he was involved in a traffic injury , accelerating all his symptoms . this led to an abuse of cocaine and amphetamine for 4 years , whereafter he was diagnosed with attention deficit and hyperactivity disorder and treated with methylphenidate . at this time clinically , he presented a superficial folliculitis with inflamed red hair follicles with surface pustules . the skin changes were found on the scalp , face , upper trunk , thighs and pubic area . at first , the patient was treated with long - term courses ( up to 6 months ) of oral tetracycline supplemented with regimes of topical antifungals ( ketoconazole shampoo 2% ) and , on separate occasions , short regimes of topical glucocorticoid ( hydrocortisone-17-butyrate and betamethasone with clioquinol , respectively ) . all initiated treatments were found to be remarkably insufficient in this patient with little or no effect on clinical findings . a skin biopsy from the back of the upper trunk was performed which showed suppurative folliculitis , primarily involving the infundibular portions of the hair follicle . periodic acid - schiff stain revealed numerous oval yeast - like organisms , thus compatible with malassezia furfur folliculitis ( fig 1 , fig 2 ) . systemic antifungal treatment included itraconazole 100 mg per day for 2 weeks with no clinical response . treatment with fluconazole , at first 150 mg every week for 8 weeks , followed by 300 mg every week for 8 weeks , showed some response , but with persisting folliculitis in the beard area . courses of systemic glucocorticoids given by the patient 's general practitioner allegedly showed good effect . however , such treatment was tapered or discontinued at the follow - ups in our clinic . two years after admission to our clinic , the patient was admitted to the department of endocrinology , odense university hospital , odense , denmark . blood tests showed low testosterone ( 3.8 nmol / l ) , low testosterone / sex hormone - binding globulin ( 0.09 ) and low luteinizing hormone ( 0.6 ui / l ) compatible with hypogonadotropic hypogonadism . also the cortisol level was low ( spot cortisol 74 nmol / l ) , with adrenocorticotropic hormone being low in the normal reference interval . several factors were suspected to have caused suppression of the pituitary gland ( use of amphetamine / cocaine , anabolic steroids , traffic injury , and use of morphine ) and therefore the exact time of onset could not be said . at first , he was given testosterone for 1.5 months without any observable effect on his skin symptoms . however , when he received both testosterone and hydrocortisone his folliculitis resolved completely in less than a month , and still after 2 years there has been no severe relapse ( fig 3 ) . pituitary insufficiency can cause isolated or multiple affection of hormonal production . in this patient , both the level of testosterone and cortisol was low . normalizing the level of testosterone did not have any effect on his skin , but shortly after hydrocortisone substitution his folliculitis resolved . it is well known that acneiform eruptions can be side effects to both systemic and strong topical glucocorticoid treatment . systemic glucocorticoid suppresses the hypothalamus - pituitary - adrenal ( hpa ) axis resulting in a reduction in endogenous cortisol production and thereby low circulating cortisol level . topical glucocorticoid also suppresses the hpa axis , although at a physiological level , and only pathologically when exceeding accepted safety guidelines . to our knowledge , it is unknown whether the low level of endogenous cortisol plays a role in the pathogenesis of acneiform eruptions during glucocorticoid treatment besides the possible direct effect of the glucocorticoid drug . studies on the direct effect of topical glucocorticoids on the development of acneiform eruptions suggest that acne is provoked by inducing rupture of the follicle where sebum seeps into the dermis . also keratinization and suppuration of follicular epithelium has been suggested as pathogenesis of glucocorticoid - induced acneiform eruptions . however , these studies are few and it remains unclear whether the previously described physiological suppression of the hpa axis is involved in the pathogenesis of topical glucocorticoid - induced acneiform eruptions . in conclusion , this case report suggests that low levels of cortisol may play a role as modifier of the inflammatory component of folliculitis and thus the pathogenesis of at least certain types of folliculitis . the authors report no conflicts of interest . there was no funding of this work .

a report on a 40-year - old patient with recalcitrant , suppurative folliculitis is presented . after years of unsuccessful treatment with conventional therapies , the patient was diagnosed with adrenal insufficiency with a low level of circulating cortisol . a few weeks after the patient was subjected to substitution therapy with hydrocortisone , his folliculitis resolved . we discuss the role of plasma cortisol level in the pathogenesis of folliculitis .

holt oram syndrome ( hos ) is a rare autosomal dominant disorder involving the hands , arms , and the heart anomalies . congenital cardiac and upper limb malformations often occur together and categorized as heart - hand syndromes . the most common of them is the hos , which characterized by septal defects of the heart and preaxial radial ray abnormalities . herein , two cases with hos are reported , the first one associated with renal agenesis , coronal hypospadias , urethral duplication and the second one associated with duodenal atresia and horseshoe kidney . written informed consents were obtained from the parents of the reviewed patients . a 7-year - old boy was admitted to our clinic with complaints of swelling and pain in his right scrotum . coronal hypospadias , left simple ear , aplasia of right thumb , and radius was seen in physical examination in addition to erythema and edema of the right scrotum [ figure 1 ] . it was learned that he had an operation for atrial septal defect ( asd ) 2 years ago . eccentric circummeatal - based ( ecmb ) flap technique and the blind ending urethra was excised . operation scar on chest wall due to atrial septal defect repair ( asterix ) , simple left ear ( arrowhead ) , and right thumb and radial aplasia ( arrow ) are shown a full - term , 3-day - old girl was admitted to the emergency department with the lack of oral intake . syndromic facial appearance , phocomelia in the bilateral upper extremities , and hypertrichosis in the left ear and left lower leg were detected in physical examination [ figure 2 ] . abdominal x - ray revealed double bubble sign , ultrasound demonstrated horseshoe kidney , and echocardiography showed a ventricular septal defect ( vsd ) . diamond - shaped duodenoduodenostomy was performed and the patient is being followed up without any complication for 20 months . a 7-year - old boy was admitted to our clinic with complaints of swelling and pain in his right scrotum . coronal hypospadias , left simple ear , aplasia of right thumb , and radius was seen in physical examination in addition to erythema and edema of the right scrotum [ figure 1 ] . it was learned that he had an operation for atrial septal defect ( asd ) 2 years ago . eccentric circummeatal - based ( ecmb ) flap technique and the blind ending urethra was excised . operation scar on chest wall due to atrial septal defect repair ( asterix ) , simple left ear ( arrowhead ) , and right thumb and radial aplasia ( arrow ) are shown a full - term , 3-day - old girl was admitted to the emergency department with the lack of oral intake . syndromic facial appearance , phocomelia in the bilateral upper extremities , and hypertrichosis in the left ear and left lower leg were detected in physical examination [ figure 2 ] . abdominal x - ray revealed double bubble sign , ultrasound demonstrated horseshoe kidney , and echocardiography showed a ventricular septal defect ( vsd ) . diamond - shaped duodenoduodenostomy was performed and the patient is being followed up without any complication for 20 months . although family history presents in 6070% of the cases and de novo mutations are present in 3040% of the cases . mutations in 12q24.1 band located in tbx5 gene that has a key role in embryonic development constitute the typical hos phenotype . upper limb abnormalities , such as phocomelia and minor thumb anomalies are also observed in all patients . in 50 - 95% of patients ostium secundum type asd , vsd , patent ductus arteriosus , heart block , and disorders such as wolff the differential diagnosis should be done from sall-4 related disorders , ulnar - mammary syndrome , vacterl / vater association , and townes - brocks syndrome because all of them have the same skeletal anomalies with hos . in addition to this , coloboma and duane anomaly in the eyes seen in sall-4 related disorders , hypogonadism seen in ulnar - mammary syndrome , vertebral , trachea - esophageal , and anal anomalies seen in vacterl / vater association ear and anal anomalies seen in townes brocks syndrome . therefore , none of these anomalies was seen in our patients , these syndromes are eliminated . to best of our knowledge , association with renal agenesis , type-1 incomplete urethral duplication and hypospadias that seen in first case and association with duodenal atresia that seen in second case has not been reported in english literature before , although some unusual associated anomalies have been described in hos such as craniofacial , tracheal , pulmonary , vertebral , renal , lower limb anomalies , cleft uvula , brain cyst , spleen anomaly , pyelon duplex , ectopic kidney , and hemivertebra . ecmb flap technique that was preferred to repair hypospadias facilitated to recognition , and excision of urethral duplication . cardiological evaluation should be done in patients with hos before surgery if required for any reason . the authors certify that they have obtained all appropriate patient consent forms . in the form the patient(s ) has / have given his / her / their consent for his / her / their images and other clinical information to be reported in the journal . the patients understand that their names and initials will not be published and due efforts will be made to conceal their identity , but anonymity can not be guaranteed . the authors certify that they have obtained all appropriate patient consent forms . in the form the patient(s ) has / have given his / her / their consent for his / her / their images and other clinical information to be reported in the journal . the patients understand that their names and initials will not be published and due efforts will be made to conceal their identity , but anonymity can not be guaranteed .

holt oram syndrome ( hos ) is a rare autosomal dominant disorder , characterized by upper limb dysplasia and congenital cardiac defect . we report two cases with hos , first associated with renal agenesis , coronal hypospadias , urethral duplication and second associated with duodenal atresia and horseshoe kidney that have not been reported in english literature .

a 38 years woman presented with abdominal pain . in evaluation colon cancer was diagnosed at stage 3 . few days after ovarian tumor resection breast tumor was diagnosed . in immunohistochemistry both ovarian and breast tumors was ck7 negative , ck20 positive , compatible with colon cancer origin . this is the first case of simultaneous metastasis of colon cancer to two rare sites . colorectal cancer most commonly metastasizes to the liver and lung and metastatic colon carcinoma ( mcc ) to the breast is extremely rare and is usually in the context of widespread disease . the development of breast metastases is exceptionally rare , account for 0.43% of all breast malignancies and is associated with poor clinical outcome . carcinomas of colon , appendix , and breast ( mainly invasive lobular carcinoma ) are the next most common primary sites . rare cases of krukenberg tumor originating from carcinomas of the gallbladder , biliary tract , pancreas , small intestine , ampulla of vater , cervix , and urinary bladder / urachus have been reported . we report a case of krukenberg tumor in a 38 years woman with colon cancer and simultaneously breast metastasis . a 38-year -old woman presented with severe generalized colicky abdominal pain and 2 - 5 times bowel habit per day . after two weeks , melena was added to her symptoms . after colonoscopy , adenocarcinoma of ascending colon fifteen months after surgery , she was developed secondary amenorrhea and was visited by a gynecologist . in pelvic sonography and then in abdominopelvic ct scan a large ovarian mass was seen ( figure 1-a ) . before this problem , both ovaries were involved and in immunohistochemistry ( ihc ) the tumor was ck7- and ck20 + ( figure 1-c & d ) , compatible with colon cancer origin . ovarian tumor ( a : ct scan b : histopathology c : ck 20 d : ck 7 ) few days after ovarian mass resection , the patient palpated one lump in her left breast . mammography was reported normal ( figure 2-a ) but sonography showed a mass in left breast . core needle biopsy was done and pathology was reported invasive breast carcinoma . mastectomy and axillary lymph node dissection was done . a 9 centimeters mass was detected and axillary lymph nodes were involved ( figure 2-c ) . in ihc , ck7 , estrogen receptor(er ) , progesterone receptor ( pr ) , e - cadherin and her-2 overexpression were negative and ck20 was positive(figure 2-d & e ) compatible with colonic origin of metastasis . the patient is symptom free after 8 months of post chemotherapy period although cea was raised without gross relapse . breast tumor ( a : mammography b : frozen section c : lymph node metastasis d : ck 20 e : ck 7 ) primary breast cancer is one of the most common malignancies but metastases to the breast from extra mammary malignancies are rare . kyoung tae noh and et al . , were found only 22 cases in searching medline and embase including non - english literature , and hand searching the references . a malignant mass in the breast can easily be misinterpreted as breast cancer and inappropriate surgical intervention could be carried out . generally , metastases to the breast from extra mammary malignancies are characterized by rapidly growing , mobile masses that are easily palpable but do not cause overlying skin or nipple retraction , or bloody nipple discharge . mammographic evaluation can be useful in the differential diagnosis of primary versus secondary breast cancer . the mammographic finding in such a case is a rounded and well - circumscribed mass . differential diagnosis between primary and metastatic breast neoplasms is not always easy . because treatment can differ profoundly , accurate diagnosis is of paramount importance to avoid unnecessary radical surgical procedures . the great majority of breast tumors are ck7 positive and ck20 negative , while colorectal carcinomas are usually ck7 negative and ck20 positive . when a breast tumor is negative for all breast markers ( er , pr , her2 , gcdp15 , bca , and ck7 ) and positive for ck20 and cdx2 , this identifies the tumor as being colon cancer metastatic to the breast . although in our patient cdx2 did not check , ihc profile confirmed colon cancer metastasis . according to recent reports , the management of metastatic breast mass from colorectal adenocarcinoma should be diagnostic and palliative . barthelmes et al . , advocated that surgical excision should be avoided in the view of short life expectancy and risk of seeding to the skin . , suggested that excisional biopsy was usually appropriate and provided adequate local control . if the diagnosis for the breast mass is unclear , unnecessary intervention , for example mastectomy or lymph node dissection of axilla , can be performed . in our case , mastectomy was done before definite diagnosis and before consult with oncologist but aggressive procedure for this patient may be one explanation for prolonged symptom free survival of the patient . it is hypothesized that this young age of diagnosis is related to the great vascularity of their ovaries , which facilitates vascular metastasis . abdominal swelling or pain usually accounted for the clinical presentation ( such as our case ) . the route of metastasis from the gastrointestinal tract to the ovaries is hypothesized to be via lymphatic . the mortality rate for krukenberg tumors is relatively high and a majority of patients die within two years of diagnosis . krukenberg tumors can be diagnosed before , after , or at the same time as diagnosis of the gi primary tumor . the prognosis worsens when the primary tumor is identified after the metastasis to the ovary is discovered . the distinction between a primary ovarian mucinous carcinoma or even a borderline mucinous tumor and a metastatic mucinous carcinoma may be difficult . a constellation of clinical , gross pathologic and morphologic features is used in this distinction . one of the most important morphologic features suggesting a metastatic mucinous carcinoma in the ovary is the presence of signet ring cells ; these are considered rare in primary ovarian mucinous tumors . features favoring a primary rather than a metastatic neoplasm are unilateral tumor , low stage , and background of adenofibroma or cystadenoma . primary ovarian tumors , usually test positive for ck 7 and negative for ck 20 in ihc . in literature review we do not found any case of colon cancer with both ovarian and breast metastases in the same time . as our knowledge we report first case of simultaneously two rare sites of colon cancer . in a patient with history of malignancy , a breast mass should be diagnosed correctly with core needle and ihc , to avoiding unnecessary mastectomy for breast metastasis .

colorectal cancer most commonly metastasizes to the liver and lung . metastatic colon carcinoma ( mcc ) to the breast is extremely rare . krukenberg tumor is an uncommon metastatic tumor of the ovary.case presentationa 38 years woman presented with abdominal pain . in evaluation colon cancer was diagnosed at stage 3 . folfox chemotherapy was done . after one year she developed krukenberg tumor . few days after ovarian tumor resection breast tumor was diagnosed . in immunohistochemistry both ovarian and breast tumors was ck7 negative , ck20 positive , compatible with colon cancer origin . this is the first case of simultaneous metastasis of colon cancer to two rare sites .

it can be used for diagnosis , prognosis or /and follow - up of diseases . biomarker is specific , sensitive and easy to measure , but finding one is not easy . one of the biggest problems when a biomarker is found is its measurement , because the concentration is usually very low , techniques are laborious and time - consuming . have been found and ongoing research is being done to prove their utility in different diseases . time - resolved amplified cryptate emission ( trace ) is a technology based on non - radiating energy transfer from donor molecule ( europium cryptate ) to acceptor molecule ( xl665 ) as a result of the completed immune reaction . the specific fluorescence which is proportional to the antigen concentration is obtained through a double selection : spectral ( separation depending on wavelength ) and temporal ( time resolved measurement ) . trace technology allows measurements in a homogeneous phase , providing precise results in a short reaction time . some of the specific novel biomarkers available with the use of trace technology are : copeptin , proadrenomedullin and proatrial natriuretic peptide . vasopressin ( avp ) is a polypeptide with a disulphide bond between the two cysteine amino acids . in humans after cleavage of the signal peptide , the resulting prohormone contains avp ( nine amino acids ) , neurophysin ii ( 95 amino acids ) and a glycopeptide ( 39 amino acids ) . at high doses it inhibits urine output with no effect on the circulation , earning its name the antidiuretic hormone. avp measurement is useful in certain endocrine disorders and as a guide therapy in pathologies in which osmotic and cardiovascular homeostasis are disturbed ( shock , sepsis ) ( 1,2 ) . however , there is a problem with its measurement that is difficult because the molecule is very unstable , largely attached to the platelets , rapidly cleared ( short half - life ) and there are variations between the assays as well . copeptin is the carboxyterminal fragment of provasopressin , a 39 aminoacid glycoprotein of yet not well - known function . as stoichiometrically released , it would reflect avp production . finally , copeptin is a more stable molecule and its assay is automated . as correlation was found between avp and copeptin concentration this allows to use copeptin as a specific novel biomarker in diagnosis of infection , severe sepsis , and septic shock in the emergency departments ( 1,2 ) . adrenomedullin ( adm ) is an almost ubiquitous peptide , extracted from a pheochromocytoma in 1993 . it has 52 aminoacids , with a disulfide bridge between the residues 16 and 21 . its main function is to decrease blood pressure , but it has many other functional actions such as : vasodilatation , increases diuresis and natriuresis , increases tolerance of cells to oxidative stress and hypoxia , stimulates angiogenesis , modulates cytokine production and exerts antibacterial action . many disease states have been associated with high levels of plasma adrenomedullin : cardiovascular ( hypertension , acute myocardial infarction , heart failure ) , respiratory ( asthma , copd ) , endocrine ( thyrotoxicosis , type i diabetes mellitus ) , renal ( chronic renal failure , glomerulonephritis ) , cancer , hepatic cirrhosis etc . measurement of adm is very difficult as it has a very short half - life , is bound to a specific protein ( binding protein h ) , adheres non specifically to the surfaces andbecause of other technical problems . adm gene is localized in chromosome 11 and is synthesized as a part of preproadrenomedullin , a 185 aminoacid precursor . during processing of preproadm other peptides are released and midregional - proadrenomedullin ( mr - proadm ) is one of them : the molecule consisting of 45 - 92 aminoacids . stoichiometrically released , this molecule may directly reflect adm concentration in plasma and is more stable ( 3 ) . atrial natriuretic peptide ( anp ) is a 28 aminoacid peptide with a 17 aminoacid ring closed by a disulfide bond between two cysteine residues ( in position 7 and 23 ) . anp is closely related to bnp ( brain natriuretic peptide ) and cnp ( c - type natriuretic peptide ) , which all share the same aminoacid ring . predominant signal for the release is atrial stretch or atrial distension due to volume expansion . besides , there are variety of other signals for its release like hypervolemia , exercise , caloric restriction , sympathetic stimulation of -adrenoreceptors , hypernatremia ( though it is not a direct stimulus ) , or a response to angiotensin - ii and endothelin . main function of proanp is to ensure relative constancy of body electrolyte and water content and circulatory homeostasis . it does so by different biological actions like vasodilatation , increasing natriuresis and diuresis , suppression of renin - angiotensin - aldosteron system , suppression of sympathetic activity and antidiuretic hormone . the peptide is synthesized as a part of preproanp , which after cleavage of signal peptide releases a 126 aminoacid precursor of anp called proanp . proanp directly reflects anp levels , is a more stable molecule and easier to measure ( 4 ) . they have been studied for diagnosis , prognosis and follow - up of many diseases : heart failure ( 5,6 ) , pneumonias ( 7 - 9 ) , copd ( 10 ) , myocardial infarction ( 11,12 ) , sepsis ( 3,13 ) , etc . some reported very good results , others not so good , and some authors conclude these biomarkers do not add any valuable information . there are much more biomarkers , like c - terminal proendothelin-1 , lipopolysaccharide binding protein , neopterin and some interleukins that are currently being investigated . some of the above presented biomarkers , are nowadays easily and quickly measured with the use of trace technology which make them helpful in the process of taking decisions in the emergency department as quickly as possible . their clinical utility has not been proven conclusively yet but in the future they might be used in the routine daily practice like other biomarkers that are nowadays in everyday use , for example c - reactive protein and procalcitonin .

the availability of an easily measurable specific marker for diagnosis of a disease is an important but not always reachable objective . emergency area is an area where decisions must be taken as quick as possible , and sometimes it is not clear if the patient is well enough to be treated as an outpatient or must be hospitalized.during last few years many new biomarkers and techniques for their measurement have been developed , and surely some others will appear . the aim of this report was to present trace technology for specific assays such as : copeptin , proadrenomedullin and proatrial natriuretic peptide . ongoing research is being done to decide in which diseases they might be useful and if they will be needed for diagnosis , prognosis or treatment monitoring . results are not conclusive yet , but in the future some of these markers could be used in routine laboratory work if their utility is documented by new data .

neurofibromatosis type 1 ( nf1 ) is a common , progressive , autosomal dominant neurocutaneous disorder characterized by variable expressivity and a predisposition to the development of tumors . clinical features include caf - au - lait macules , skin - fold freckles , lisch nodules , and dermal neurofibromas . chronic myeloid leukemia ( cml ) is a clonal stem cell disorder characterized by increased proliferation of myeloid cells and the presence of philadelphia chromosome . the natural history of cml is one of progression from a chronic phase via an accelerated phase to blast crisis , the blast crises is often refractory to treatment . this chromosome leads to reciprocal translocation between chromosomes 9 and 22 , juxtaposing the bcr and abl genes onto chromosome 22 , producing a fusion protein with abnormal tyrosine kinase activity ; leading to a proliferative advantage in the affected cells . children with nfi have about 500 times greater risk of developing a malignant myeloid disorder than the normal children . nf-1 has been associated with nonlymphocytic leukemia such as juvenile myelomonocytic leukemia , myelodysplastic syndrome , and acute myeloid leukemia ( aml ) in children . childhood acute lymphoblastic leukemia ( all ) has been reported rarely in association with familial nf-1 , with sporadic nf-1 showing a higher incidence of all than nonlymphocytic leukemia . the ratio of all to nonlymphocytic leukemia patients was 5:3 among sporadic nf-1 and 4:15 among patients with familial nf-1 . however , this association between nf1 and malignant blood disorders has rarely been demonstrated in adults . a study by julia et al . reported two adults who developed aml over a 10-year period , none developed cml , all , or chronic lymphocytic leukemia . increased levels of ras - gtp are found in the nf1-associated leukemias , these leukemic cells show hypersensitivity to gm - csf and other cytokines . a literature search carried out in pubmed did not reveal any report of cml in adults with nf1 . our patient was a 37-year old female teacher who was first seen in the hematology outpatient clinic following a referral from the dermatology clinic where she was being managed for type 1 neurofibromatosis ( nf1 ) . she presented with a 6-month history of easy fatigability and a left - sided abdominal mass . she had lost more than 10% of her weight in the past 6 months , and also complained of night sweats . our patient was married with three children ; there was no history of nf in either her nuclear or extended family . on examination , she was chronically ill - looking and pale , afebrile to touch with caf - au lait spots over her trunk and lower limb , she also had neufibromas over her trunk [ figure 1 ] . presence of neurofibroma on the patient 's back the result of her full blood count is shown in figure 2 , peripheral blood film and marrow aspirate were consistent with cml in chronic phase [ figure 3 ] . a fish analysis for bcr / abl translocation showed that all 200 of her cells screened were positive for the bcr / abl signal . result of full blood count done for the patient over time bone marrow aspirate cytology showing spectrum of myeloid maturation while awaiting her fish analysis result , she was started on 2 g hydroxyurea ( hu ) daily , 300 mg allopurinol daily , and liberal oral fluids of at least 3l over 24 h. she was on hydroxyurea for about 6 months with fairly good results as shown in figure 2 . when her fish result was obtained , she was subsequently placed on 400 mg glivec daily . the patient did not tolerate glivec for very long , as she developed a pancytopenia , worst affected were the platelet count , she then started bleeding from the gums and developed menorrhagia , clotting profile done was normal apart from the presence of thrombocytopenia . glivec was stopped and she was recommenced hu with poorer results this time , wbc did not respond and continued to rise . bone marrow aspirate confirmed that she had progressed into the blast state attempts at inducing remission with aml regimen failed . the nf1 gene ( a tumor suppressor gene ) encodes neurofibromin which has a gtpase - activating protein ( gap ) domain that regulates the action of ras proteins . ras proteins are signal switch molecules regulating cycling between an active guanosine triphosphate ( gtp)-bound state ( ras - gtp ) and an inactive guanosine diphosphate ( gdp)-bound state ( ras - gdp ) . people with nf1 are at increased risk for the development of malignancies such as leukemia , rhabdomyosarcoma , optic glioma , and brain tumors . given the relative common incidence of nf1 and the fact that patients with this disease have been shown by several authors to be predisposed to developing malignant diseases , it is difficult not to associate the cml which our patient developed with the underlying nf1 process ; although to the best of our knowledge this association has not been previously made in an adult . it is possible that there was a synergistic action between the absence of neurofibromin and the presence of the tyrosine kinase activity of the bcr / abl gene . we are unable to explain why she ran a rather poor course , since other patients with cml and the philadelphia chromosome have fared a lot better when placed on glivec . we conclude that dermatologist and other physicians that mange patients with nf1 should remain at alert about the possibility of their patients developing cml along with other malignancies .

patients with neurofibromatosis type 1 ( nf1 ) , a common , progressive , autosomal dominant neurocutaneous disorder , are predisposed to malignancies . several types of hematologic malignancies have been described in them . however , to date there has been no report to the best of our knowledge of a patient with nf1 developing chronic myeloid leukemia ( cml ) . we present an adult ghanaian with nf1 , who subsequently developed cml . relevance of the case report is discussed .

to report a case who had recurrence of macular hole retinal detachment ( mhrd ) after intravitreal ranibizumab injection ( ivr ) for the treatment of choroidal neovascularization ( cnv ) that arose from the damaged retinal pigment epithelium of the remaining macular hole ( mh ) edge , which had been successfully treated by pars plana vitrectomy ( ppv ) 15 years previously . a 67-year - old man with previous ppv for mhrd secondary to high myopia in the right eye had been under observation for 15 years after surgery . ppv with an additional internal limiting membrane peeling , removal of the cnv membrane and 20% sf6 gas tamponade was performed . one year after the last surgery , his right retina was attached and the mh was closed successfully . we propose that patients who undergo ivr should be carefully maintained and followed up for possible complications including the recurrence of mhrd . intravitreal anti - vascular endothelial growth factor ( vegf ) agent therapy for age - related macular degeneration ( amd ) , proliferative diabetic retinopathy ( pdr ) and neovascular glaucoma ( nvg ) is widely used . on the other hand , retinal pigment epithelium ( rpe ) tears [ 1 , 2 , 3 ] and worsening of tractional retinal detachment ( rd ) [ 4 , 5 , 6 ] have been reported as a result of the contractile forces of regressing neovascular membranes after intravitreal anti - vegf agent injection . however , the mechanism of construction of the fibrovascular membranes remains to be elucidated . in this report , we present a case who had recurrence of macular hole retinal detachment ( mhrd ) after intravitreal ranibizumab injection ( ivr ) for the treatment of choroidal neovascularization ( cnv ) that arose from the damaged rpe of the remaining macular hole ( mh ) edge . a 67-year - old man with previous pars plana vitrectomy ( ppv ) for mhrd secondary to high myopia in the right eye ( od ) had been under observation for 15 years after the surgery . slit lamp examination revealed pseudophakia in od and mature cataract in the left eye ( os ) . best corrected landolt ring chart visual acuity ( bcva ) was from 0.1 to 0.2 in od and 30 cm finger motion in os . the patient presented with sudden vision loss in od . on presentation , funduscopic examination revealed a disciform rpe atrophy formation at the bottom of the remaining mh and cnv development around the edge of mh from the superior to temporal side ( fig . his bvca was not worsening but his subjective symptom was getting worse day by day . funduscopic examination showed cnv contraction to the superior edge and recurrence of mhrd from the inferior edge of the remaining mh ( fig . emergency ppv with an additional internal limiting membrane peeling , removal of cnv and 20% sf6 gas tamponade was performed on the same day . extraction of cnv was performed under the patient 's written informed consent , the approval of the institutional review board in kobe kaisei hospital and the tenets of the declaration of helsinki . one year after the last surgery , his right retina was reattached and mh was closed successfully ( fig . 1c , e , h ) . rpe tears and worsening of tractional rd after intravitreal anti - vegf agent therapy have been reported [ 1 , 2 , 3 , 4 , 5 , 6 ] . several reports hypothesized that intravitreal anti - vegf agent therapy may cause severe contract force of the neovascular membrane followed by rpe tear in amd [ 1 , 2 , 3 ] and tractional rd in pdr [ 4 , 5 , 6 ] . it is possible that the contract force of the regressing cnv might be increased after ivr , thereby causing rd from the remaining mh edge in our case . in our case , we performed emergency ppv with cnv removal to fix the detached retina because the visual acuity in os was bad and the mhrd in od was expanding . for the treatment of cnv , it might be one of the options to continue ivr because ivr is thought less invasive compared with cnv removal during ppv . but if we perform additional ivr first , it is very important to make the cnv inactive before the following ppv because ivr itself may cause recurrence of mhrd due to the contract force of the cnv again . we must follow - up this patient for at least another month after the injection to confirm the effect of ivr . unfortunately , we had not a moment to lose in this case . we performed ppv with cnv extraction and achieved both retinal reattachment and the quieting effect of the cnv . in summary , we propose that patients who undergo ivr should be carefully maintained and followed up for possible complications including the recurrence of mhrd .

purposeto report a case who had recurrence of macular hole retinal detachment ( mhrd ) after intravitreal ranibizumab injection ( ivr ) for the treatment of choroidal neovascularization ( cnv ) that arose from the damaged retinal pigment epithelium of the remaining macular hole ( mh ) edge , which had been successfully treated by pars plana vitrectomy ( ppv ) 15 years previously.case reporta 67-year - old man with previous ppv for mhrd secondary to high myopia in the right eye had been under observation for 15 years after surgery . the retina had been successfully attached , but the mh remained open . he had cnv which arose from the remaining mh edge . ivr was performed for the treatment of cnv . one month after the injection , cnv was contracted but recurrence of mhrd occurred . ppv with an additional internal limiting membrane peeling , removal of the cnv membrane and 20% sf6 gas tamponade was performed . one year after the last surgery , his right retina was attached and the mh was closed successfully.conclusionwe propose that patients who undergo ivr should be carefully maintained and followed up for possible complications including the recurrence of mhrd .

anhidrosis is the inability to produce or deliver sweat despite appropriate thermal or pharmacological stimuli . generalized anhidrosis may occur secondary to congenital absence of sweat glands ( ie , anhidrotic / hypohidrotic ectodermal dysplasia ) , metabolic disorders ( e.g. fabry disease ) , and secondary anhidrosis as a result of connective tissue disease ( e.g. sjgren syndrome ) , chronic dermatoses by plugging of eccrine duct ( e.g. , psoriasis or atopic dermatitis ) , panautonomic neuropathy , underlying neurologic disorders with autonomic dysfunction ( e.g. multiple sclerosis or shy drager syndrome ) , peripheral neuropathies ( e.g. diabetes mellitus , guillain barre syndrome ) , and drugs ( e.g. anticholinergic or psychotropic agents ) or it can be idiopathic . we report a patient with idiopathic - acquired generalized anhidrosis that is caused due to destruction of sweat glands . a 47-year - old male patient presented with cutaneous burning sensation on heat exposure and absence of sweating for past 3 years . he gave history of profuse sweating in the past , which gradually decreased to a point when there was no sweating for past 3 years . he was previously working as a clerk , but for past 3 years heat intolerance prevented him from going out during day time . he gives a history of dryness of eyes , for which ophthalmology evaluation was done and schirmer 's test was found to be negative . cutaneous examination showed violaceous papules and plaques in both lower limbs suggestive of lichen planus . systemic examination showed bilateral pupils were normal , equally reacting to light , accommodation reflex and extraocular muscle function were found to be normal . investigations including complete hemogram , liver and renal function test , thyroid function tests were found to be normal . peripheral smear , x - ray skull and bone marrow studies were done and were found to be normal . skin biopsy from apparently normal anhidrotic skin showed the absence of eccrine sweat glands [ figures 1 and 2 ] . this patient was started on oral prednisolone for lichen planus , but his anhidrosis obviously showed no improvement . acquired idiopathic generalized anhidrosis , first described by lutembacher in 1919 , is a rare condition characterized by the absence of sweating . since then , there are a few reports of the same . the typical patient is a young japanese male , presenting with cutaneous burning sensation , heat intolerance and absence of sweating . various pathomechanisms proposed were idiopathic sudomotor dysfunction , sudomotor neuropathy , sweat gland abnormalities and occlusion of proximal duct . the histopathology of reported cases shows marked variation , there can be normal appearing eccrine glands , eccrine gland atrophy , perieccrine lymphocytic or mast cell infiltrates , irregular arrangement of glands or occlusion of proximal duct . in our patient there was a history of profuse sweating in the past followed by generalized anhidrosis for a period of 3 years and the histopathology showed the characteristic absence of sweat glands . we explored various causes for anhidrosis , but could not find any to explain the absence of sweating . while in the course of the disease , the patient developed lesions of lichen planus . lichen planus is an autoimmune disease and may be associated with various other autoimmune diseases . so we propose an autoimmune origin of acquired generalized anhidrosis , similar to autoimmune thyroiditis . in autoimmune thyroiditis , initially there is hyperthyroidism followed by a phase of hypothyroidism . similarly in this case there is hypersecretion ( profuse sweating ) followed by the absence of sweating . hence , we put forth an autoimmune - mediated destruction of eccrine sweat glands in a patient with lichen planus as a plausible hypothesis to explain the anhidrosis . these autoantibodies may be directed either against the eccrine glands itself or its nerve supply , causing a destruction leading to the absence of previously normally functioning eccrine glands . the treatment options tried are systemic steroids , gabapentine , cyclosporine , antihistamines , with variable results . in this case we gave oral prednisolone , lichen planus lesions improved , but anhidrosis did nt show much improvement as sweat glands were absent . acquired idiopathic anhidrosis occurring in association with lichen planus may be due to autoimmune destruction of eccrine glands

acquired idiopathic generalized anhidrosis is a rare condition , where the exact pathomechanism is unknown . we report a case of acquired idiopathic generalized anhidrosis in a patient who later developed lichen planus . here an autoimmune - mediated destruction of sweat glands may be the probable pathomechanism .

she was a known case of myopic choroidal neovascular membrane ( cnvm ) , which was treated with a photodynamic therapy and avastin anti - vascular endothelial growth factor intravitreal injection in both eyes 2 years ago . her best corrected visual acuity was 20/100 , n6 in both the eyes ( refractive error : 15.00 ds and 13.00 ds for right and left eye respectively ) . on examination following mp evaluation , she underwent mp-1 biofeedback training for 10 sessions each 10 min , on alternate days , for both eyes . a written informed consent was taken , and an approval from the institutional review board was obtained . distance visual acuity , near visual acuity , fixation , and mp tests were assessed again at the end of the biofeedback training ( i.e. , after 20 days ) and at the follow - up , a year later . mp was repeated using the follow - up function , which automatically retested the patient in exactly the same locations . the mp and fixation test were performed using mp-1 microperimeter ( nidek technologies ; podua , italy ) in central 20 area . the stimulus attenuation ranged from 0 to 20 db with goldmann size iii stimulus , the size of the target was kept 5 according to her visual acuity . each eye was assessed separately for fixation behavior , location and stability of the prl , scotoma size and density and central light sensitivity . to assess the fixation stability , movements of the fundus were tracked during the examination while the patient gazed at the fixation target [ fig . 1 ] . the autotracking system calculated the horizontal and vertical shifts relative to a reference frame and mapped the patient 's eye movements during the examination . mp audio biofeedback training was performed by asking the patient to move her eyes according to an audio feedback , which advised whether the patient was getting closer to the desired final fixation position . microperimetry-1 image of color topography and stability of fixation at baseline , end of the biofeedback training and at 1-year follow - up . fixation characteristics were taken as described by fuji et al . ; the standard of central fixation was defined to approximate a 2 diameter ( equals , 600 ) circle centered on the fovea . the scotoma density was defined based on the threshold values : normal function - threshold values of 10 db ; relative scotoma - threshold values of 10 db and an absolute scotoma was present if no threshold could be seen . best corrected visual acuity was 20/100 in both eyes before and after training and the same was maintained till the follow - up after a year . the mean retinal sensitivities before , after and at 1-year after training in the right eye were 2.9 db , 2.9 db and 3.7 db and in the left eye were 3.5 db , 3.7 db and 1.8 db . the fixation point in the 2 gravitation circle , following biofeedback training improved from 40% to 50% in the right eye and from 43% to 67% in the left eye . the prl , which was superior to the scotoma prior to and following the training , was maintained at the follow - up visit . the average eye speed , which was 0.19/s before bfd training , changed to 0.26/s following bfd training in the right eye and remained at 0.25/s at the follow - up visit . the average eye speed reduced from 0.36/s to 0.25/s in the left eye following bfd training and remained at 0.27/s at the follow - up visit [ figs . 2 and 3 ] . ( a ) fixation behavior in center 2 area 40% before training with average eye speed of 0.19/s . ( b ) fixation behavior in center 2 area 50% after biofeedback training with average eye speed of 0.26/s . ( c ) fixation behavior in center 2 area 65% at 1-year of follow - up training with average eye speed of 0.25/s left eye : fixation distribution : graph of fixation points versus radius in degree . ( a ) fixation behavior in center 2 area 43% before training with average eye speed of 0.38/s . ( b ) fixation behavior in center 2 area 50% after biofeedback training with average eye speed of 0.25/s . ( c ) fixation behavior in center 2 area 75% at 1-year follow - up with average eye speed of 0.27/s the fixation location was predominantly eccentric in the right eye before training ; it was poor central following bfd training and was maintained at 1-year follow - up . the fixation location was poor central in the left eye before training ; it was poor central following bfd training and was predominantly central at 1-year follow - up . this is the first report from india , which estimates the benefits of low vision rehabilitation using mp-1 bfd in macular pathology . this case showed good response after the bfd training , which was maintained at 1-year follow - up . our results showed that new prl ( trl ) increased fixation stability as well as retinal sensitivity . no significant changes in the visual acuity , mean retinal sensitivity and speed of eye movement were seen . nilsson et al . found an improvement in reading speed following eccentric viewing training demonstrated with scanning laser ophthalmoscopy microperimeter ( 9.0 5.868.3 19.4 with p < 0.001 ) . frennesson et al . used computer and video display based system for training eccentric viewing in macular degeneration with an absolute central scotoma , which showed a significant increase in reading speed . the bfd effect can be related to the brain 's ability to perceive an efficient prl for visual tasks . the audio feedback can help the brain to fix the trl by increasing the attentional modulation . sound perception increases the conscious attention of the patient , thereby facilitating the lock - in of the visual target and increasing the permanence time of the target itself on the retina . this mechanism probably facilitates stimuli transmission not only between intraretinal neurons , but also between the retina and brain where the highest degree of stimuli processing takes place , thereby supporting a remapping phenomenon . in summary , this case demonstrated successful biofeedback training in macular pathology . further studies are needed to evaluate the usefulness of this technique in bilateral macular diseases .

microperimetry-1 ( mp-1 ) evaluation and mp-1 biofeedback training were done in a case of bilateral myopic macular degeneration with a central scotoma . fixation behavior , location and stability of preferred retinal locus , eye movement speed , and mean sensitivity were assessed . the mean retinal sensitivities before , after and at 1-year after training in the right eye were 2.9 db , 2.9 db and 3.7 db and in the left eye were 3.5 db , 3.7 db and 1.8 db . the fixation point in the 2 gravitation circle , improved from 40% to 50% in the right eye and from 43% to 67% in the left eye . the average eye speed before , after and at 1-year after training in right eye were 0.19/s , 0.26/s and 0.25/s and in left eye were 0.36/s , 0.25/s and 0.27/s . thus , biofeedback training using mp-1 can improve the visual function in patients with macular diseases and central scotoma .

giant serpentine aneurysm was described in 1977 by segel and mclaurin14 ) as a subcategory of giant aneurysms , distinct from the saccular variety . patients with a large or giant aneurysm of the internal carotid artery ( ica ) located in the paraclinoid area often present with cranial nerve symptoms . cavernous ica aneurysms can have a mass effect on the oculomotor , trochlear , or abducens nerve , resulting in internal or external ophthalmoplegia . it is most likely associated with carotid ophthalmic or hypophyseal aneurysms , but rarely occurs with a cavernous ica aneurysm . we report a patient with a serpentine cavernous ica aneurysm who presented with visual symptoms that progressively improved after endovascular coil trapping . a 44-year - old woman presented with decreased right visual acuity of 1-month duration . two weeks previously , she had complained of dry eye and was diagnosed with optic neuritis at a private clinic . the examination showed a decrease in her right visual acuity to 0.04 compared to 1.0 on the left side . the right visual field showed a 3/4 defect involving all but the right lateral upper quadrant . on magnetic resonance imaging ( mri ) of the brain , a large aneurysm , 19 12 mm in size , well marginated , and oval - shaped , with a heterogeneous signal void was seen in the right parasellar region , probably in the cavernous sinus ( fig . computed tomography angiography ( cta ) showed fusiform dilatation of the right cavernous ica , suggestive of a fusiform aneurysm with an approximate size of 30 20 mm ( fig . fundus photography showed right optic nerve atrophy with a pale neural rim on the right optic disc ( fig . the findings on transfemoral catheter angiography ( tfca ) were similar to those obtained with mri and cta . 4a ) , followed by observation of the collateral flow during temporary occlusion of the parent artery . after 20 min , the collateral flow was deemed tolerable . the patient was then evaluated by single - photon emission computed tomography ( spect ) . because the results showed well - maintained vascular reserve ( fig . 4b ) , we chose to perform coil embolization of the large serpentine aneurysm with occlusion of the parent artery ( fig . postoperatively , the patient had no obvious neurological deficits . a second round of mri and spect 24 h after the embolization showed no abnormalities . nine months after coil embolization , the patient 's visual field and visual acuity had improved considerably ( table 1 , fig . radiologically these aneurysms may be serpentine , whereas macroscopically they may be referred to as large fusiform aneurysms , and pathologically as dissecting , atherosclerotic , or dysplastic . this confusion about the exact nature of the aneurysm can be resolved by considering the natural history , clinical presentation , and treatment rationale . patients with dissecting intracranial aneurysms typically present with subarachnoid hemorrhage and have a high incidence of early rebleeding.12 ) however , patients with large fusiform lesions present with a progressive mass effect and are at less risk of suffering hemorrhage.1)16 ) the imaging features of large serpentine aneurysms are also characteristic.1)11 ) computed tomography shows an extra - axial mass originating from the artery with intramural thrombosis . magnetic resonance imaging shows a heterogeneous oval mass , indicative of thrombi of different ages , and a " flow - void " lesion with an enhanced rim . there are several reports of surgical ( hunterian ) ligation , trapping , resection , and thrombectomy with and without vascular bypass.2)4)8)14)16 ) surgical removal alone is a direct , attractive treatment . several therapeutic options have been reported.1)3)9)13)14 ) however , the perioperative morbidity and mortality are 30 - 35% . one reason is the difficulty preserving the surrounding vessels during surgical dissection and excluding the aneurysm from the normal cerebral vasculature . in addition , the functionally distal areas of the brain are supplied by the channel within the serpentine aneurysm . therefore , the goal of surgical treatment is the elimination of the blood flow to the aneurysm and maintenance of the blood flow to the distal cerebral territory . first , the surgical dissection to expose the aneurysm may require aggressive retraction , resulting in brain injury . second , adjacent important neurovascular structures can be compressed by the aneurysm and may adhere tightly to its surface . third , the neck of a serpentine aneurysm can be difficult to identify in the surgical field . some large serpentine aneurysms have been managed successfully using endovascular procedures intended to induce thrombosis and shrinkage of the mass.1 ) this is an indirect treatment strategy compared with surgical removal , but it has several advantages . an endovascular treatment does not require extensive retraction that can cause injury of the normal cerebral tissue due to microsurgical dissection . furthermore , an endovascular treatment can be used to obtain clear angiographic images to visualize the serpentine vascular channels on the aneurysm surface . clinical improvement following endovascular occlusion of an aneurysm causing a mass effect has been reported in > 75% of cases.5)6)7)10)11 ) a dramatic decrease in aneurysm size is a common finding on mri after successful endovascular occlusion.15)17 ) one report suggested that occlusion of the parent artery is more effective at decreasing the volume and relieving the mass effect than is endosaccular occlusion,17 ) which may result in the accumulation of embolic material in the aneurysm , thereby limiting shrinkage of the aneurysm . nevertheless , endosaccular obliteration has been effective in reducing the mass effect.10 ) it has the advantage of preserving the normal brain and vascular structures . , we did not clearly differentiate whether the pathogenesis of the visual disturbance involved embolism from the aneurysm itself or pulsatile compression by the aneurysm sac . however , our patient with a serpentine aneurysm presenting as a visual disturbance was treated by endovascular trapping . this was a better therapeutic choice than proximal occlusion because trapping can block both anterograde and retrograde flow , potentially reducing intra - aneurysmal pressure and promoting thrombogenesis . careful studies were performed before trapping , using cross - compression and balloon occlusion to evaluate the cerebral hemodynamics . however , in patients with poor collateral flow , extracranial - intracranial bypass surgery should be considered . nonetheless , even in those cases , endovascular trapping is a useful option , particularly when performed in combination with bypass surgery . we described the case of a patient with a large serpentine aneurysm who presented with visual disturbances . this patient was treated successfully with coil embolization after careful studies of the intracranial hemodynamics .

this report describes a case of a serpentine fusiform aneurysm of the internal carotid artery in a patient who presented with visual disturbances . the serpentine aneurysm was treated successfully by coil trapping and occlusion of the parent artery , accompanied by balloon dilation . nine months post - operatively , the patient 's visual acuity had improved considerably .

the prowess ( recombinant human activated protein c worldwide evaluation in severe sepsis ) trial demonstrated a 6.1% absolute decrease in mortality with a p value of 0.005 . recombinant activated protein c ( rhapc ) was approved by the fda for use in patients with ' sepsis induced organ dysfunction associated with a high risk of death , such as an apache [ acute physiology and chronic health evaluation ] ii of 25 ' . apache ii 25 was used as one marker of high risk of death because a subset data analysis demonstrated that the treatment benefit in the prowess trial was predominantly in this group of patients . the european regulatory body approved rhapc for multiple organ failure ( again based on subset data analysis from the prowess trial demonstrating increased treatment effect as the number of organ failures increased ) . the surviving sepsis campaign ( ssc ) guidelines for the management of severe sepsis and septic shock recommend the use of rhapc in patients with high risk of death due to sepsis - induced organ dysfunction . since the publication of the ssc guidelines additional large clinical trials of rhapc have concluded : the enhance ( extended evaluation of recombinant human activated protein c ) , address ( administration of drotrecogin alfa ( activated ) in early stage severe sepsis ) and pediatric trials [ 3 - 5 ] . the enhance trial provided supportive evidence for the favorable benefit / risk ratio observed in the prowess trial and suggested that earlier therapy was more effective . the enhance trial also revealed a somewhat greater incidence of serious hemorrhage with rhapc than was evident in the prowess trial . the results of the address trial , designed with the purpose of prospectively studying the effect of rhapc in patients with severe sepsis at low risk of death , supported the fda labeling that rhapc was not of utility in such patients . however , a post hoc subset analysis of patients who were admitted to a trial designed to target a low risk of death but who also had an apache ii 25 failed to show benefit in this group . the fda labeling recommends use in patients with sepsis - induced organ dysfunction and at high risk of death but only goes as far as identifying patients with apache ii 25 as an example of such a group . patients at high risk of death from severe sepsis would indeed seem the appropriate target group for rhapc . the ssc recommendation lists four groups of patients that satisfy high risk of death : acute respiratory distress syndrome , septic shock , multiple organ failure and apache ii 25 . prowess enrolled patients with single and multiple organ failure , apache ii 25 and apache ii < 25 , and enrolled patients who could have been classified a priori as having either high or low clinical assessment of risk of death . unfortunately we do not know what the assessments of risk of death were because clinicians treating the patient were not required to make that assessment and it was not part of the data collection . the fda then recommended the use of rhapc in patients at high risk of death and required a repeat trial in patients at low risk of death . the specified intent of the address trial was to enroll patients at low risk of death , which would typically be those with single organ failure and lower apache ii , whereas the prowess study had patients that clinicians could have clinically assessed as being at high risk of death and others at low risk of death . perhaps if there had been an a priori assignment of clinical assessment of risk of death in the prowess trial , the effect of rhapc in these patients would have been enhanced . so the key to patient selection for administration of rhapc might be a priori assessment of risk of death . septic shock , acute respiratory distress syndrome ( ards ) and multiple organ failure are typically those states that would make a clinician clinically assess a patient as high risk of death . or should we garner direction by looking at subgroup analyses of the prowess trial as to which patient groups appeared to benefit ( septic shock , apache ii 25 , multiple organ failure and thrombocytopenia ) . how does one balance or blend clinical assessment of high risk of death ( prowess minus address patient populations ) against subset analyses from prowess . is apache ii 25 alone , regardless of risk of death assessment , a valid criterion for patient selection ? this issue has been raised by the address trial results ; however , it must be remembered that this analysis in the address trial was a post hoc subset analysis . if the address trial was the only randomized prospective trial so far performed and the only group that showed benefit in that trial was the apache ii 25 subgroup ( as a post hoc subset analysis ) , no one would be arguing that it should be used in that group . it is even more interesting when we recognize that the advocates of this line of thinking are now using a post hoc subset analysis from one trial to refute a post hoc subset analysis from another trial ! so perhaps the apache ii was never appropriate for patient identification from the start . which is more important in identifying risk of death prospectively : a clinical assessment of risk of death or apache ii scoring ? the prowess trial had no inclusion criteria related to clinical assessment of risk of death . in that trial there was a 44% mortality rate in placebo patients with apache ii 25 whereas in the address trial , which targeted the enrollment of patients with a clinical assessment of a low risk of death , the mortality was 25% in the apache ii 25 group . this suggests that the key is clinical assessment of death and not apache ii score . patients with recent surgery and single organ dysfunction who received rhapc had significantly higher 28-day mortality rates ( 20.7% versus 14.1% , p = 0.03 , n = 635 ) . should this address post hoc subset analysis also influence our prescribing of rhapc as being different in surgery patients ? if this had been the only subgroup that was different in the address trial but the post - hoc subset analysis had shown benefit instead of harm , would we be recommending that it be used in this group ? if we let this influence our practice , should it be only for post - operative patients with clinical assessment of low risk of death and single organ failure ? in my opinion the decision on administration of rhapc should be based on a seasoned clinician 's clinical assessment of high risk of death from sepsis - induced organ failure and acceptable risk of bleeding complications . typically high risk of death will be associated with septic shock , ards or multiple organ failure . address = administration of drotrecogin alfa ( activated ) in early stage severe sepsis ; apache = acute physiology and chronic health evaluation ; ards = acute respiratory distress syndrome ; enhance = extended evaluation of recombinant human activated protein c ; prowess = recombinant human activated protein c worldwide evaluation in severe sepsis ; rhapc = recombinant activated protein c ; ssc = surviving sepsis campaign . rpd serves as a non - reimbursed member of the steering committee of the surviving sepsis campaign , whose activities are partly funded by unrestricted educational grants from industry , including eli lilly , makers of rhapc . in addition , he has received one honorarium from eli lilly over the past two years for a non - product - oriented lecture at the invitation of a regional medical society .

the prowess ( recombinant human activated protein c worldwide evaluation in severe sepsis ) trial demonstrated a 6.1% absolute decrease in mortality with a p value of 0.005 . despite the impressive results of this trial , criticism of the study has targeted various aspects of design , analysis and interpretation . additional studies of recombinant activated protein c ( rhapc ) have added to our understanding about this drug and to controversy as well . so how do we deal with rhapc use in our clinical practice ?

gastric endoscopic submucosal dissection ( esd ) is well established for the standard treatment of early gastric cancer , yet colorectal esd is not because of the technical difficulty and the high risk of complication . however , the number of performing colorectal esd is steadily increasing , and thus this may become popular soon . colorectal esd is particularly valuable to resect large laterally spreading tumors ( lsts ) containing mucosal cancer or shallow submucosa - invading cancer . in 2011 , korean health insurance review and assessment service began to cover gastric esd when the procedure is performed for the standard indication . colorectal esd was also approved as an acceptable treatment option , but did not obtain reimbursement . colorectal esd was introduced in korea around 2003 , and now major training hospitals and specialized colorectal hospitals perform this procedure to some level . three results of colorectal esd in korea which were published in the science citation index journals1,2 demonstrated that the case numbers were 108 to 499 cases at each institution , en bloc resection rates were 78.7% to 95.0% , and perforation rates were 4.5% to 20.4% . rectal mucosal tumors and shallow submucosa - invading cancers had been treated by transanal excision or transanal endoscopic microsurgery ( tem ) , however these days rectal esd cases were becoming popular since rectum is the easiest and the safest site for the esd . in the results comparing rectal esd and tem , both esd and tem were useful and oncologically safe for treating lst type rectal carcinoma in situ and shallow submucosa - invading cancers.3 however , esd has the additional advantage in that it is minimally invasive and does not require anesthesia , abundant use of antibiotics , and longer hospital stay . in terms of complication , esd seemed safer because this procedure is less invasive while tem involves resection of proper muscle . therefore , esd could be a primary option for a treatment of superficial early rectal cancers . korean health insurance review and assessment service began to reimburse for the gastric esd from november , 2011 and admitted extended criteria for the colorectal esd but did not reimburse for it . the extended criteria for the colorectal esd which was approved by korea health insurance include early colorectal cancer which has no metastasis to the regional lymph nodes , lsts equal to or larger than 2 cm , submucosal tumors , and tumors with fibrosis . specialist of the relevant department who has 3-year experience after obtaining the special license should perform esd and the institution should have facilities for immediate open abdominal surgery in case of emergency situation . after esd , registration of esd cases and reporting pathology reports describing histologic diagnosis including degree of differentiation , depth of cancer invasion , presence of lymphovascular invasion , status of the resection margin , and the size of the resected specimen , are obligatory . colorectal esd is still in its early phase of introduction , but is increasing steadily in korea . standard indication , qualified training system , and full medical insurance coverage should be established for the procedure to become popular .

colorectal endoscopic submucosal dissection ( esd ) is not yet fully popularized in korea , but is increasing steadily . the outcomes of colorectal esd in korea are comparable to those in japan and other countries . esd - related complication rates are decreasing as experiences accumulate . particularly for rectal laterally spreading tumors , esd is becoming more prevalent than transanal endoscopic microsurgery . standard indication , qualified training system , and full medical insurance coverage should be established for the procedure to become popular in the long run .