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skeletal muscle metastasis as the initial presentation of an unknown primary lung cancer is unusual . f-18 fluorodeoxyglucose ( fdg ) positron emission tomography / computed tomography ( pet / ct ) imaging is useful in the identification of primary in carcinoma of unknown origin . we describe a patient showing fdg - avid metastases to the skeletal muscles along with a previously unknown primary tumor in the right lung , in a patient presenting with initial muscular symptoms without any pulmonary manifestations . the patient underwent a whole body f-18 fdg pet / ct to identify the site of the primary malignancy . increased fdg avidity ( standardized uptake value [ suvmax ] 9.0 ) was detected in an irregular heterogeneously enhancing soft - tissue mass in the right paravertebral region in the upper lobe of the right lung with a focus of calcification within the mass [ figure 1b and d , white arrow ] . abnormal fdg uptake was also noted in a presacral mass [ figure 1c and e ] , the bulky left adrenal gland , several dorsal vertebrae and multiple lesions in the trapezius [ figure 1b and d , red arrow ] , right brachioradialis [ figure 2 ] , deltoid , and right external oblique muscles [ figure 3 ] , suggestive of metastatic involvement . a diagnosis of primary squamous cell carcinoma of the lung was pathologically the patient was treated with 4 cycles of chemotherapy , after which significant decrease in fdg uptake ( suvmax = 5.1 ) was seen in the primary as well as the right brachioradialis muscle lesion ( not shown here ) . fluorodeoxyglucose ( fdg ) positron emission tomography / computed tomography ( pet / ct ) maximum intensity projection ( mip ) image ( a ) showing multiple foci of abnormal tracer uptake . transaxial thoracic ct ( b ) and fused pet / ct image ( d ) show increased fdg uptake in an irregular , heterogeneously enhancing soft - tissue mass ( white arrow ) in the paravertebral region in the upper lobe of the right lung with calcification within the mass . increased fdg uptake is also seen in a peripherally enhancing ring like lesion in the trapezius ( red arrow ) . axial ct ( c ) and fused pet / ct ( e ) images at the level of the rectum show increased fdg uptake in a heterogeneously enhancing pre - sacral soft - tissue deposit coronal and transaxial computed tomography ( ct ) ( a and c ) and fused positron emission tomography / ct ( b and d ) images of the right hand showing increased fluorodeoxyglucose uptake in the right brachioradialis muscle with no increase in attenuation ( probably because the images were acquired after completion of the whole body pet scan ) axial computed tomography ( a ) and fused positron emission tomography / computed tomography ( b ) images showing increased tracer uptake in a ring - like hyperenhancing lesion in the right external oblique muscle suggestive of muscle metastasis found that only 4 patients ( 0.16% ) among 2,557 patients with lung cancer developed metastasis to the skeletal muscle . whole - body fdg pet / ct imaging is useful in detection of muscle metastases in lung cancer patients . multiple muscle metastases from lung cancer are rare , and fdg pet / ct imaging is useful in the identification of unsuspected metastatic sites . primary presentation of a skeletal muscle metastasis , such as in our case , remains an unusual occurrence . the present case , where the initial presentation was of metastatic muscular involvement , highlights the role of fdg pet / ct in tracing the location of primary lung malignancy and unsuspected sites of multiple muscle metastases in a patient with muscle metastases of unknown primary .

skeletal muscle metastasis as the initial presentation of the unknown primary lung cancer is unusual . a 65-year - old male patient presented with pain and swelling of the right forearm . fine needle aspiration of the swelling revealed metastatic squamous cell carcinoma . the patient underwent whole body f-18 fluorodeoxyglucose ( fdg ) positron emission tomography / computed tomography ( pet / ct ) to identify the site of the primary malignancy . the authors present pet / ct images showing fdg - avid metastases to the skeletal muscles along with a previously unknown primary tumor in the right lung , in a patient presenting with initial muscular symptoms without any pulmonary manifestations .

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although it comprises only 10 - 15% of all hepatobiliary neoplasms , its incidence is increasing.1 frequent metastatic sites of biliary cancer are the liver , peritoneum , intra - abdominal lymph nodes , and lungs.2 here , we describe a very rare case in which metastatic cholangiocarcinoma of the stomach was mistaken for primary gastric cancer in a patient who underwent whipple 's operation . however , histopathologic and immunohistochemical findings suggested that the gastric tumor was a metastatic adenocarcinoma originated from a distal cholangiocarcinoma . a 67-year - old woman presented with a 4-month history of abdominal pain after meals . laboratory findings was as follows : aspartate aminotransferase 141 iu / l ( normal ; 10 - 40 iu / l ) and total bilirubin 0.9 mg / dl ( 0.2 - 1.0 mg / dl ) . computed tomography showed a malignant tumor of the common bile duct ( cbd ) , located just above the intrapancreatic segment , with consequent dilatation of the proximal biliary tree including the gall bladder ( fig . 1 ) . the periportal , common hepatic , and portocaval lymph nodes were enlarged . endoscopy revealed a 2-cm , flat , elevated lesion with convergence of the surrounding folds , situated at the gastric angle ( fig . based on the biopsy results , an adenocarcinoma , thought to be an early gastric cancer , was diagnosed . the patient underwent whipples 's operation . the surgical specimen consisted of a whitish mass , 2.11.3 cm in diameter , removed from the distal cbd and showing invasion of the pancreas and peripancreatic fat . pathologic examination of the resected stomach demonstrated that the tumor was very clearly demarcated from the surrounding nontumorous gastric mucosa and submucosa , and also showed invading lymphovascular spaces . in addition , the adenocarcinomatous tissue had infiltrated into the gastric mucosa and submucosa , while the gastric superficial mucosa was intact ( fig . immunohistochemical stains showed that the tumor tissue was strongly positive for cytokeratin ( ck)-7 and weakly positive for ck-19 , while the surrounding gastric mucosa was negative for both cytokeratins ( fig . according to a number of reports in the literature , metastasis to the stomach is a rare occurrence , with a reported incidence of less than 1% . the main primary metastatic tumors are those of the breast ( 33% ) and lung ( 25% ) , and malignant melanoma ( 22%).3 in our patient , it was difficult to distinguish gastric metastasis of a cholangiocarcinoma from a primary gastric cancer on the basis of clinical , endoscopic , and radiologic features . thus , results obtained from complete histopathologic and immunohistochemical studies of gastric biopsies should be compared with the characteristic features of cancer of the cbd . the anatomic distribution of ck-7 and ck-19 is generally restricted to epithelia of primary sites and their neoplasm . primary gastric cancer has the same staining pattern , because ck-7 and ck-19 expressions are reported to be positive in about 80% of stomach cancer cases . however , both the normal gastric mucosa surrounding the tumor and the gastric carcinoma , if it originates from the stomach , are positive for ck-7 and ck-19.4,5 metastasis to the gastrointestinal tract initiates from the serosa and submucosa and progresses to cause intraluminal lesions , as occurred in this case.6 based on these considerations , we diagnosed metastatic gastric carcinoma from a distal cholangiocarcinoma . another important immunohistochemical marker , cdx-2 is a very useful marker to distinguish stomach cancers from bile duct cancers , because cdx-2 expression is reported to be positive in 61% of stomach cancer cases but only in 13% of bile duct cancers , however cdx-2 was not performed in our study.7 until now , unusual metastastic sites from cholangiocarcinoma were reported to be the colon , adrenal gland , skull bone , epididymis , corneal limbus , meninges , ovary , skeletal musle , and skin.2,8 - 15 metastasis of a distal cholangiocarcinoma to the stomach has not been reported previously to our knowledge but , as in the above - mentioned sites , appears to be a rare site of metastasis of this tumor . in conclusion , a careful histopathologic and immunohistochemical review is very important in diagnostic differentiation of metastatic tumors from primary sites in this case .

we report an unusual case of distal cholangiocarcinoma with gastric metastasis mimicking early gastric cancer . a 67-year - old woman presented with a 4-month history of abdominal pain after eating . computed tomography showed a malignant tumor of the common bile duct located just above the intrapancreatic segment , and endoscopy revealed a 2-cm , flat , elevated lesion with convergence of the surrounding folds , situated at the gastric angle . based on the endoscopic biopsy results , an adenocarcinoma , thought to be an early gastric cancer , was diagnosed . the patient underwent whipples 's operation . histopathological findings showed that the adenocarcinomatous tissue was clearly demarcated and infiltrated the gastric mucosa and submucosa , leaving the gastric superficial mucosa intact . both tumors showed similar pathological features and were positive for cytokeratin ( ck)-19 and ck-7 . these finding suggest distal cholangiocarcinoma with gastric metastasis .

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diphenyl cyclo propenone ( dpcp ) is used as a topical immunomodulator in alopecia areata . it is a potent contact allergen in humans and animals ; 98 - 99% of the cases of alopecia areata can be sensitized on the scalp skin . although its use has been increasing of late , the process of procuring , dilution and storage at a particular concentration is cumbersome and limits its wide use . this short communication aims to make the dpcp preparation and application easy for the readers . dpcp is available as 1 and 5 g powder in amber - colored glass bottles . the standard solvent , acetone , is a strong uv light absorber and inhibits this process . for dilution , first , the dpcp is weighed in a weighing scale and then diluted with the required quantity of acetone . initial sensitization is carried out with a 2% solution , which is made by dissolving 20 mg in 1 ml of acetone . further dilution can be prepared by making a stock solution of 2% and diluting with acetone taken in a pipette as per the concentration [ tables 1 and 2 ] . dilution for diphenyl cyclo propenone dilution from the stock solution 2% percentage = weight / volumedilution100 ( % = w / vdilution100 ) to prepare a 0.001% solution , 0.1 ml of stock solution is mixed with 200 ml of acetone , and 5 ml of the resulting solution can be used for application over the scalp . the rest of the solution should be stored in air tight , screw - capped amber - colored containers for further use . storage of the diluted solution is difficult as acetone often evaporates , leading to a change in the concentration . fresh solution can be made every time to avoid this . for concentrations of 0.01% and above , dpcp can be weighed prior and stored in glass containers to which acetone can be added in the required amount at the time of application as this saves time and prevents wastage ( e.g. , 0.01% can be made by adding 10 ml acetone in 1 mg preweighed dpcp containers ) . the diluted solutions are placed in a wide - mouthed glass beaker and applied on the scalp with cotton swab . application needs to be done fast to cover the entire scalp before acetone starts evaporating in the beaker . health care professionals should take proper precautions of wearing a glove , face mask and apron during the dpcp application as the spill of solution may cause an irritant / urticarial reaction . patients are advised to wait for 5 - 10 min in the out patient department before covering their head with a cap or cloth to protect from sunlight . after 48 h , patients should be advised to shampoo the scalp to remove the residual dpcp . during these 48 h , patients should be advised not to touch the scalp accidentally either by themselves or others . the common adverse effects after dpcp applications are local eczema with blistering , regional lymphadenopathy and contact urticaria . rare adverse effects include an erythema multiforme - like reaction , hyperpigmentation , hypopigmentation and vitiligo .

diphenyl cyclo propenone ( dpcp ) is used as a topical immunomodulator in alopecia areata . it is a potent allergen . the process of procuring , dilution and application limits its wider use . this short communication aims to make the dpcp application easy to use .

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during 20042007 , as part of a broader biodiversity survey and inventory program , we sampled birds from mostly forested sites in guangxi and guizhou provinces in the southern part of the people s republic of china ( figure ) . sampling was conducted by mist netting and selective harvesting with shotguns ; all birds in the study were apparently healthy and behaving normally at the time of collection . because initial sampling was focused on endoparasite communities , samples from 20042005 consisted of complete gastrointestinal tracts frozen in liquid nitrogen . in 20062007 southeastern asia , showing 5 sites in the people s republic of china where land birds were collected and tested for influenza a virus . prevalence values were 4% ( n = 103 ) in dashahe in 2006 ; 6% ( n = 194 ) in kuan kuoshui in 2006 ; 0.3% ( n = 328 ) in shuipu in 2007 ; 3% ( n = 184 ) in jing xi , in 2004 ; and 0% ( n = 130 ) in shiwandashan in 2005 . a total of 184 samples were collected from jing xi municipality in guangxi ( 21.122n , 105.964e ) in 2004 , 130 from shiwandashan nature reserve in guangxi ( 21.840n , 107.880e ) in 2005 , 103 from dashahe nature reserve in guizhou ( 29.167n , 107.575e ) in 2006 , 194 from kuan kuoshui nature reserve in guizhou ( 28.226n , 107.160e ) in 2006 , and 328 from shuipu village , guizhou province ( 25.485n , 107.882e ) in 2007 ( figure ) . samples were tested for influenza a virus by real - time reverse transcription pcr ( 6 ) in 2 diagnostic laboratories ( southeast poultry research laboratory , us department of agriculture , athens , ga , usa , and national wildlife health center , us geological survey , madison , wi , usa ) . of 939 samples tested , 24 were positive for influenza a viruses ( prevalence 2.3% , table ; complete summary in appendix table ) . if migratory behavior ( species classified as migratory or nonmigratory on the basis of descriptions by mackinnon and phillipps ) , was considered , 11 ( 4.8% ) of 231 samples from species showing marked seasonal migrations were influenza positive . however , only 13 ( 1.8% ) of 708 samples from nonmigratory species were positive . the cumulative binomial probability that such a high number ( 11 ) of positive samples would result among the 231 migratory - species samples , were the true prevalence to be 1.8% , is low ( p = 0.0013 ) . thus , migratory species appear to have higher influenza infection rates . in terms of general habitat use ( 7 ) , open - country species were slightly more prone to be influenza positive ( 8 [ 2.9% ] of 274 samples ) than forest species ( 16 [ 2.4% ] of 665 samples ) , but the difference was not significant ( cumulative binomial probability , p>0.05 ) . interactions between migratory behavior and habitat use were not significant ( contingency test , p>0.05 ) . although all infections detected were among songbirds ( passeriformes ) , the sampling also concentrated on songbirds ( 94.3% ) . thus , we could not test adequately the hypothesis that influenza prevalence was equivalent between songbirds and other birds . an obvious question is whether the influenza a viruses we detected belong to the highly pathogenic subtype h5n1 strain currently circulating across much of asia . pcr ( 6 ) , although this result does not exclude the possibility that h5 viruses were among the positive samples . the preservation status of samples we tested prevented virus isolation or full , strain - level characterization of influenza viruses . the subtype h5n1 strain of influenza virus has spread rapidly and has been detected across much of central and southern eurasia . although movements of wild birds have been implicated in this spread ( 8) , other studies question ( 9,10 ) or contradict ( 11 ) this idea . an important part of the argument centers on the question of the occurrence of the virus in wild birds without obvious illness , which can be difficult to interpret given the low prevalence of influenza . for instance , a recent study based on sampling > 13,000 migratory birds in china detected the subtype h5n1 strain of influenza virus only 8 times ( 12 ) , and similar results have been obtained elsewhere ( 2 ) . our study , although not successful in characterizing influenza viruses to specific strains , nonetheless shows that influenza a virus infection occurs in more bird species than previously assumed and that influenza a infections can be found in birds that behave normally and show no sign of illness . although a review of avian influenza virus ecology ( 1 ) discussed the occurrence of influenza viruses across all groups of birds ( and other vertebrates ) , subsequent studies have assumed that waterbirds are the primary reservoir ( 8,13,14 ) . in this study , although waterbirds could have higher prevalences , we have demonstrated broad occurrence of influenza viruses in diverse taxa of passeriformes ( songbirds ) in southeast asia . this result suggests that land birds may also be a major reservoir of influenza viruses . we have taken a step toward a more complete understanding of influenza virus ecology among wild birds . our partial survey of influenza virus distributions across the rich avifaunas of the southern region of china demonstrated frequent infections . we suggest that to be effective future surveillance efforts will need to include the full diversity of wild birds .

water birds are considered the reservoir for avian influenza viruses . we examined this assumption by sampling and real - time reverse transcription pcr testing of 939 asian land birds of 153 species . influenza a infection was found , particularly among migratory species . surveillance programs for monitoring spread of these viruses need to be redesigned .

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peutz - jeghers is a rare autosomal dominant disorder characterized by hamartomatous polyps and discoloration of mucosal membranes . the polyps can occur anywhere in the gastrointestinal tract and can grow large enough to cause bowel obstructions . a 16-year - old male presented to the emergency department with signs and symptoms of an acute bowel obstruction . he had a previous history of a colonoscopy with polypectomy at age 4 , and hyperpigmentation of his mucous membranes . an exploratory laparoscopy found an intussusception of the mid jejunum . a laparoscopic - assisted small bowel resection was performed . colonoscopy and upper endoscopy revealed 5 more polyps in the stomach and colon that were removed . the treatment of obstruction in these patients is to remove the offending hamartomatous polyp(s ) . the rest of the intestine needs to be examined and those polyps found should be removed . peutz - jeghers syndrome ( pjs ) is a rare autosomal dominant condition characterized by hamartomatous polyps and mucocutaneous pigmentation of the lips , buccal mucosa , and digits . polyps can occur anywhere in the gastrointestinal tract and can grow large enough to cause bowel obstructions . a 16-year - old male presented to the emergency department with signs and symptoms of an acute bowel obstruction . he had a previous history of a colonoscopy with polypectomy at age 4 , had hyperpigmentation of his mucous membranes , and his mother and maternal grandfather had a history of gastrointestinal polyps . the patient underwent an exploratory laparoscopy and was found to have an intussusception of the mid jejunum ( figure 1 ) . pathology showed a 5-cm polyp that had acted as a lead point for the intussusception ( figure 2 ) . the patient had an uncomplicated postoperative course and was discharged home on postoperative day 3 . he is one year out from surgery and has resumed his normal activities with no evidence of recurrence . pjs was first described in 1921 by peutz and subsequently elaborated upon by jeghers in 1949 . germline defects in the tumor suppressor gene serine / threonine kinase 11 ( stk11 ) are implicated in this rare autosomal dominant inherited disease . its incidence is calculated in 1 in 200,000 liveborns , and its mean age of onset is 25.2 years . the most common location of the hamartomatous polyps is the small bowel ( 78% ) , followed by the colon ( 42% ) , stomach ( 38% ) , and rectum ( 28% ) . these polyps can cause obstruction in up to 43% of cases and rectal bleeding in up to 14% of patients . the syndrome is associated with a 2% to 10% increased risk of cancer of the intestinal tract , from the stomach to the rectum . there is also an increased risk of extraintestinal malignancies , including cancer of the breast , ovary , cervix , fallopian tubes , thyroid , lung , gallbladder , bile ducts , pancreas , and testes . however , recurrence of intussusception episodes occurs in at least 10% of cases , resulting in repeated surgical intervention . thus , the rest of the intestine needs to be examined , and those polyps found should be removed . once the gastrointestinal tract has been cleared of polyps , the recommended interval of small bowel follow - through is from 2 years to 3 years . the presence of polyps larger than 1.5 cm in diameter mandates another complete gastrointestinal evaluation with endoscopic removal of polyps . patients should also be screened periodically for malignancies of the breast , cervix , ovary , testis , stomach , and pancreas . to our knowledge , there are at least 2 other published case reports regarding the laparoscopic management of bowel obstructions in pjs . the ideal way to remove a pedunculated polyp acting as a lead point , laparoscopy offers a safe and effective method for surgical management with reduction of the intussusception and small bowel resection . the diagnosis of pjs should be considered in patients presenting with a clinical picture of bowel obstruction and mucocutaneous hyperpigmentation . if the diagnosis is made preoperatively , optimal management should include laparoscopic treatment of the bowel obstruction and intraoperative enteroscopy . if the diagnosis is made after the operation , the patient needs complete evaluation of their gastrointestinal tract .

introduction : peutz - jeghers is a rare autosomal dominant disorder characterized by hamartomatous polyps and discoloration of mucosal membranes . the polyps can occur anywhere in the gastrointestinal tract and can grow large enough to cause bowel obstructions.case report : a 16-year - old male presented to the emergency department with signs and symptoms of an acute bowel obstruction . he had 2 days of abdominal pain , obstipation , and vomiting . he had a previous history of a colonoscopy with polypectomy at age 4 , and hyperpigmentation of his mucous membranes.results:computed tomographic ( ct ) scan revealed an intussusception of the small intestine . an exploratory laparoscopy found an intussusception of the mid jejunum . a laparoscopic - assisted small bowel resection was performed . pathology showed a 5-cm polyp that acted as a lead point for the intussusception . colonoscopy and upper endoscopy revealed 5 more polyps in the stomach and colon that were removed.conclusion:small bowel obstructions can be managed successfully with minimally invasive approaches . the treatment of obstruction in these patients is to remove the offending hamartomatous polyp(s ) . the rest of the intestine needs to be examined and those polyps found should be removed . this can be done intraoperatively with laparoscopic - assisted enteroscopy and colonoscopy .

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today , the treatment of choice is surgical excision of the tongue , but before 1900 , surgery was often temida1 . only in 1673 niels the size and shape of the teeth are directly influenced by the size of tongue3 . the shape of the teeth is determined by forces employed on the teeth , especially the muscles of the tongue , lips and cheek . due to the effects caused by the aesthetic and functional macroglossia the macroglossia is classified as true when there is excessive enlargement of the language and a relative when there is an imbalance between the size of the tongue and oral cavity , resulting in insufficient space for organ4 . the goal is to establish technical bases associated with partial glossectomy orthodontic treatment of dentofacial deformity in patients with macroglossia . three patients underwent orthognathic surgery associated with partial glossectomy from 1995 to 1999 , a multidisciplinary team - doctor and dentist . all patients had macroglossia relative and underwent clinical assessment taking into account the respiratory function , swallowing and speech deficit , as well as changes in dental occlusion and was also performed radiological evaluation . the main problem was manifested by the presence of steep lower dent alveolar , destabilizing the use of dentures causing joint dysfunction with severe pain . she underwent a single surgical intervention in the partial glossectomy and orthognathic surgery for targeting sub apical segment dent alveolar anterior inferior . the main problem of the second patient was the anterior open bite accompanied by difficulty in breathing and articulation of words . after treatment for orthodontic tooth alignment leveling , underwent surgery for a single suspension by corticotomy posterior maxillary le fort i type , reduction of mandibullary prognathism by sagittal technical branches , targeting sub apical posterior - inferior right and partial glossectomy . the third patient had mandibullary prognathism and , during orthodontic treatment in preparation for orthognathic surgery , the surgery was anticipated , since the interposition of the tongue between the back teeth did not allow the evolution of orthodontic treatment . he underwent a partial glossectomy to reduce the transverse diameter of the tongue and mandibullary prognathism by sagittal technical branches . we used rigid skeletal fixation with titanium plates and screws so that patients could stay without intermaxillary block in the immediate postoperative period . to control tongue edema , the technique used consist of segmental resection along the median raphe of the tongue and suture by planes - figure 1 . as a routine the symptoms regressed completely and all skeletal segments remained stable . demarcation and resection of the lingual and final appearance . the classification of macroglossia is not yet consensus in the literature . according to shafer ( 1968)5 , or primary congenital macroglossia is due to the excessive development of the musculature , which may or may not be associated with generalized muscular hypertrophy or unilateral hypertrophy . since the secondary macroglossia may occur as a result of a tumor in the tongue , as a diffuse hemangioma or lymphangioma , neurofibromatosis , and occasionally blocking efferent vessels in cases of malignant neoplasm of the tongue . wolford et al . ( 1996)6 refer to as macroglossia on pseudomacroglossia , separating it from the true macroglossia . ( 1980)7 macroglossia consider the functional as a third classification , occurring when the language does not fit into the oral cavity after a surgical procedure . the true when there are histological abnormalities associated with the increase of the tongue , such as vascular malformation , stretching and tumors . relative macroglossia includes cases of apparent increase in volume without an explanation of the language exam , as in down syndrome . the decision to refer the patient to partial glossectomy should be based on the volume of the language , mobility , position , function , symptoms , speech intelligibility , skeletal anterior open bite , interference in orthodontic treatment , drooling , swallowing and tongue recurrent trauma9 . the language has increased in volume expansive effect on the lower dental arch , being blamed as the cause and maintenance of open bite , bimaxillary protrusion or diastemas10 . being interposed between the arches , is an important etiologic factor for malocclusion listed ( figures 2 and 3 ) . a partial glossectomy performed simultaneously with mandibullary osteotomy for treatment of patients with mandibullary prognathism and anterior open bite is advantageous to prevent recidivas11 . the tongue can cause deformity increased dental - muscle - skeletal , instability in orthodontic treatment and orthognathic surgery , masticatory disability , communication problems and respiratory6 . there are several clinical and radiographic findings , but not all features are always present and their existence is not necessarily path gnomonic for the diagnosis of macroglossia . should be included the clinical , radiographic and functional for the interference with speech , mastication , airway and stability of orthodontic treatment and orthognathic surgery . there are basically three choices in the surgical sequence : ( i ) stage 1 : partial glossectomy , stage 2 : orthognathic surgery ( ii ) stage 1 : orthognathic surgery , stage 2 : partial glossectomy and ( iii ) partial glossectomy and orthognathic surgery in a single stage surgery .

summary introduction : macroglossia is a condition which influences the size and shape of the teeth employed due to the forces on teeth . objective : to establish bases for the indication of partial glossectomy associated with orthodontic treatment and surgical dento - facial deformity in patients without tumors and down syndrome as a cause of macroglossia . case reports : three patients underwent orthognathic surgery associated with partial glossectomy under general anesthesia . all patients had macroglossia relative and underwent clinical assessment taking into account the respiratory function , swallowing and speech deficits and radiological evaluation . the technique used consist of segmental resection along the median raphe of the tongue and suture by planes . we used rigid skeletal fixation with titanium plates and screws so that patients could stay without intermaxillary block in the immediate postoperative period . were followed over five years . the symptoms regressed completely and all skeletal segments remained stable . discussion : the decision to refer the patient to partial glossectomy should be based on the volume of the language , mobility , position , function , symptoms , speech intelligibility , skeletal anterior open bite , interference in orthodontic treatment , drooling , swallowing and tongue trauma applicant .

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these viruses infect a variety of species , including aquatic birds , poultry , pigs , horses , dogs , and humans , causing significant morbidity and mortality . in the case of human influenza viruses , in addition to the burden of yearly epidemics , there is the ever - present threat of an influenza pandemic . pandemics occur when a novel strain of influenza virus of animal origin evolves the ability to infect and efficiently transmit among humans . while some influenza pandemics , like the 1918 h1n1 pandemic that killed more than 40 million people worldwide , have had devastating consequences , others , including the h1n1 pandemic in 2009 , which resulted in an estimated 18,000 deaths , have been considerably milder . unfortunately , the emergence of new human pandemic viruses , as well as the subtype and virulence of the causative viruses , is still unpredictable . although there are vaccines available for certain influenza viruses , they are strain specific , and the generation and general distribution of a new influenza virus vaccine take more time than the spread of a new virus , severely limiting the impact of vaccines in the first wave of a pandemic . influenza antiviral drugs are of broader specificity , but resistance to those drugs and problems with availability limit their use . in order to mitigate the possible impact of an influenza pandemic , we need more research and development in the generation of improved vaccines and antivirals with broad cross - reactivity against multiple influenza viruses . in addition , by investigating the factors responsible for the generation of human pandemic viruses , we can better recognize the risks that animal influenza virus strains pose to humans and build eradication campaigns to target specific viral strains circulating in animals . critical to this issue is the question of what makes an influenza virus transmissible in humans and animals . a better understanding of influenza transmission will lead to the development of countermeasures for viral transmission that can enhance our pandemic preparedness plans . several mutations and changes associated with increased airborne transmission of avian influenza viruses in ferrets have been identified in recent years ( 13 ) . however , previous attempts to identify adaptive changes in highly pathogenic avian h5n1 viruses associated with transmission have failed , supporting the possibility that h5n1 viruses might be structurally unfit for mammalian transmission ( 4 ) . more recently , two independent laboratories lead by ron fouchier and yoshihiro kawaoka have ruled out this hypothesis and identified specific mutations that allow the h5n1 virus to accomplish airborne transmission in ferrets ( unpublished observations ) . while this provides important information on the adaptability of h5n1 viruses , more research needs to be conducted to understand the possibility that avian h5n1 could evolve to become transmissible in humans , to predict its pathogenesis in humans , and to find the molecular mechanisms responsible for host specificity in influenza virus transmission . while research on influenza virus transmission is critical for finding ways to better tackle this pathogen , it is important to conduct such research using appropriate biocontainment and biosafety conditions to minimize possible risks of virus release to the environment . risk assessment is a crucial tool in selecting biocontainment levels for research on potentially dangerous pathogens . according to the biosafety in microbiological and biomedical laboratories ( bmbl ) manual ( 5 ) , the definitive reference book for biosafety issues , biological risk associated with pathogen research is determined by three elements : the activities that can result in human exposure to the pathogen , the probability that such exposure would cause an infection , and the consequences of such an infection . although ferret - adapted h5n1 viruses probably have attenuated infectivity and pathogenesis for humans , to minimize all possible risks one should use biocontainment facilities and practices that prevent human exposure . preventing the escape of viruses from the laboratory can be achieved by housing research activities in a facility equipped with interlocked rooms with negative pressure and high - efficiency particulate air ( hepa ) filtered air circulation and using the appropriate decontamination and/or sterilization practices for material leaving the facility . since human infection with influenza viruses occurs via the respiratory route , infection of laboratory personnel can be prevented by the use of powered air - purifying respirators . these practices correspond to enhanced biosafety level 3 ( bsl3 ) , as described in the bmbl manual . the effects of accidental exposure to the virus in an enhanced bsl3 facility can be minimized by vaccinating personnel with an h5n1 vaccine and through the use of antiviral drugs . increased biocontainment , or bsl4 , h5n1 viruses , on the other hand , are sensitive to the antivirals zanamivir and oseltamivir , and infection with the virus is preventable by vaccination with the h5n1 inactivated vaccine . influenza virus research is important for the development of novel intervention strategies for preventing and mitigating influenza epidemics and pandemics . as scientists , we have the responsibility to avoid the undue restrictions of the highest level of biocontainment if enhanced bsl3 facilities can provide the appropriate biosafety . the use of bsl4 containment would not decrease the risk of virus release any more than enhanced bsl3 containment , but it would result in an unnecessary burden that would restrict research on h5n1 influenza transmission to a few facilities and considerably decrease the speed of research on this important pathogen .

abstractresearch on h5n1 influenza viruses has received much attention recently due to the possible dangers associated with newly developed avian h5n1 viruses that were derived from highly pathogenic avian viruses and are now transmissible among ferrets via respiratory droplets . an appropriate discussion , based on scientific facts about the risks that such viruses pose and on the biocontainment facilities and practices necessary for working safely with these viruses , is needed . selecting the right level of biocontainment is critical for minimizing the risks associated with h5n1 research while simultaneously allowing an appropriately fast pace of discovery . rational countermeasures for preventing the spread of influenza can be developed only by gaining a thorough knowledge of the molecular mechanisms at work in host specificity and transmission .

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selenium , from the greek word selene ( meaning moon ) , is a chemical element ( atomic number 34 ) that was discovered as a by - product of sulfuric acid in 1817 . in 1967 , it was found that the thyroid gland had the maximum amount of selenium per gram of tissue . autoimmune thyroiditis ( ait ) , the prototype of autoimmune diseases , is characterized by t - cell - mediated autoimmune destruction of thyroid cells . environmental factors , such as iodide intake , immunotherapeutic agents , or viral infections that may initiate the disease . in areas , where selenium deficiency is prevalent , higher incidence of thyroiditis has been reported due to a decreased activity of selenium - dependent glutathione peroxidase enzyme within thyroid cells . severe nutritional selenium deficiency leads to an increased rate of thyroid cell necrosis and invasion of macrophages . whether this it may be assumed , however , that thyroid cell damage may initiate or maintain autoimmune thyroiditis , especially in patients susceptible to the development of autoimmune diseases . to study the effect of selenium supplementation in patients with autoimmune thyroid disease . patients of all age groups and both sexes with autoimmune thyroid disease ( as defined by an anti- thyroid peroxidase antibody [ tpoab ] level more than 150 iu / ml ) irrespective of the baseline thyroid status . patients with overt hyperthyroidism who are on antithyroid drugs , patients on any other medication , which may alter the immunity status of the patients , and pregnant patients were excluded from the study . patients were randomized into two age and tpoab - matched groups ; 30 patients received 200 g sodium selenite / day , orally , for 3 months , and 30 patients received placebo . the differences in antibody concentrations at the beginning and end of the study were determined by t - test for paired samples . patients of all age groups and both sexes with autoimmune thyroid disease ( as defined by an anti- thyroid peroxidase antibody [ tpoab ] level more than 150 iu / ml ) irrespective of the baseline thyroid status . patients with overt hyperthyroidism who are on antithyroid drugs , patients on any other medication , which may alter the immunity status of the patients , and pregnant patients were excluded from the study . patients were randomized into two age and tpoab - matched groups ; 30 patients received 200 g sodium selenite / day , orally , for 3 months , and 30 patients received placebo . the differences in antibody concentrations at the beginning and end of the study were determined by t - test for paired samples . in the selenium treated group 27 patients were female , and three patients were male ( m : f = 1:9 ) , which was comparable with the ratio in the placebo - treated group ( 1:7.3 ) the mean ages at presentation in both the groups were 34 2.5 and 31 3.4 years , respectively . at study entry , the mean tpoab concentrations were identical for both groups ( selenium treated group , 669 205 iu / ml ; placebo , 729 277 iu / ml ) . out of the total 30 patients in the selenium treated group , 6 patients were overtly hypothyroid , 15 were subclinical hypothyroid , 6 were euthyroid , and 3 were subclinical hyperthyroid . there were comparable numbers of patients in each subgroup in the placebo - treated group also . the mean tpoab concentration decreased significantly by 49.5% ( p < 0.013 ) in the selenium treated group versus 10.1% ( p < 0.95 ) in the placebo - treated group . in subgroup analysis , the decrease in the mean tpoab titre was highest in the subclinical hyperthyroid group ( up to 64.42% ) , and comparable in the other three groups ( 41.13% , 47.18% , and 42.64% in the euthyroid , hypothyroid , and subclinical hypothyroid groups respectively ) . one patient with hypothyroidism in the selenium treated group with a tpoab concentration of > 1000 iu / ml , had completely normalized antibody concentrations after 3 months . it was also found that those patients with tpoab greater than 1000 iu / ml revealed a mean 31.38% reduction in the selenium - treated patients , compared with no significant change in tpoab in the placebo group . . glutathione peroxidase can reduce hydrogen peroxides and phospholipid hydroperoxides , and hence can reduce the production of free radicals and reactive oxygen species . these mechanisms may contribute to reduced inflammatory activity in the organ - specific autoimmune response , and may explain the improvement of autoimmune thyroiditis in our study . based on the link described above between selenium and the thyroid , several studies applying organic and inorganic selenium compounds were undertaken in patients , with ait in areas with low to borderline - low - selenium content . a prospective placebo - controlled clinical study with selenium in ait conducted in the selenium deficient area of bavaria in southern germany , by grtner et al . in 2002 showed a 36% reduction in anti - tpo titers in the selenium - treated group , whereas a further reduction of up to 60% was seen in a subgroup of patients with basal anti - tpo levels above 1200 iu / ml . supplementation of selenium has a significant impact on inflammatory activity in thyroid - specific autoimmune disease . it would be of interest to determine whether early treatment with selenium in patients with newly developed autoimmune thyroiditis may delay , or even prevent the natural course of these diseases .

introduction : in areas with severe selenium deficiency higher incidence of thyroiditis has been reported due to a decreased activity of selenium - dependent glutathione peroxidase enzyme within thyroid cells.aims and objective : to study the effect of selenium supplementation in patients with autoimmune thyroid disease.materials and methods : this is a blinded placebo - controlled prospective study done in 60 patients with autoimmune thyroid disease ( as defined by an anti - thyroid peroxidase antibody ( tpoab ) level more than 150 iu / ml ) irrespective of the baseline thyroid status . patients with overt hyperthyroidism who are on antithyroid drugs , patients on any other medication , which may alter the immunity status of the patients , and pregnant patients were excluded from the study . patients were randomized into two age and tpoab - matched groups ; 30 patients received 200 g of sodium selenite / day , orally , for 3 months , and 30 patients received placebo . all hypothyroid patients were given l - thyroxine replacement.results:of 30 patients in the selenium treated group , 6 patients were overtly hypothyroid , 15 were subclinical hypothyroid , 6 were euthyroid , and 3 were subclinical hyperthyroid . the mean tpoab concentration decreased significantly by 49.5% ( p < 0.013 ) in the selenium treated group versus 10.1% ( p < 0.95 ) in the placebo - treated group.conclusion:selenium substitution has a significant impact on inflammatory activity in thyroid - specific autoimmune disease . it would be of interest to determine whether early treatment with selenium in patients with newly developed autoimmune thyroiditis may delay or even prevent the natural course of these diseases .

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acute acalculous cholecystitis ( aac ) is defined as acute inflammation of the gallbladder in the absence of gallstones and has a multifactorial pathogenesis.1 aac occurs in about 10% of all cases of acute cholecystitis . aac has numerous causes that produce bile stasis and ischemia leading to inflammation and infection of the gallbladder . aac tends to have a more fulminant course , is frequently associated with gangrene , perforation and empyema , and has high morbidity and mortality.2 aac has traditionally been recognized to occur in patients with serious co - morbid illnesses especially after a major operation , severe trauma , burns , systemic sepsis and prolonged intravenous hyperalimentation.3 however , there has recently been an increasing number of reports in the literature of the occurrence of aac in patients with none of the established risk factors.4 - 6 aac arising as a complication of laparoscopic appendectomy has been reported in just 1 case and it was treated conservatively.7 herein , we present the case of a 38-year - old woman who developed aac after laparoscopic appendectomy . a 38-year - old woman who was previously in good health came to our emergency room 3 days after she received laparoscopic appendectomy at a local clinic . she had acute abdominal pain which initially occurred in the epigastric and umbilical area and then migrated to the right lower quadrant after 10 hours and was associated with nausea and anorexia . acute appendicitis had been diagnosed by abdominal computed tomography ( ct ) and operative findings at another hospital . her abdominal pain and associated symptoms improved after surgery . body temperature was 37.8. she exhibited tenderness and guarding in the epigastric region and right upper quadrant . results of the laboratory studies were unremarkable , except for elevated c - reactive protein ( crp ) which was 8.04 mg / dl ( normal range less than 0.5 mg / dl ) . her body mass index ( bmi ) was 21.7 ( height : 168 cm , weight : 61.2 kg ) . abdominal ct showed a thickened , contrast - enhanced wall of the gallbladder ( fig . her abdominal pain subsided and crp decreased to 1.33 mg / dl after the ptgbd . the patient 's postoperative progress was uneventful , and she was discharged 5 days after surgery . aac generally occurs in patients after major surgery , in the presence of critical illnesses such as trauma , burns , and sepsis , and in the elderly.1 however there have been recent reports of acalculous cholecystitis in young healthy patients who had none of the established risk factors.6,8 the patient described in this case report was young and healthy and exhibited none of the standard risk factors other than recent surgery , although laparoscopic appendectomy is not considered to be a major operation . the commonest postulated pathogenesis of aac is bile stasis resulting in a change of bile composition and ischemia.2 factors known to contribute to bile stasis in the postoperative patient are fasting , anesthesia , dehydration , fever , and narcotics for the relief of pain.9 i believe that the most probable mechanism of aac in this woman was bile stasis that resulted from the anesthesia given to her during the appendectomy and the narcotics given for the relief of pain . aac is difficult to diagnose because clinical signs such as abdominal pain and fever , and laboratory test results are non - specific . delayed diagnosis of aac is associated with high morbidity and mortality due to the high prevalence of gangrene and perforation.10 early diagnosis and appropriate treatment can improve outcomes in patients with aac.11 the treatment options for aac are cholecystostomy and/or cholecystectomy.9,12 cholecystectomy generally is considered the definitive therapy , and percutaneous cholecystostomy can be performed safely and rapidly.9 standard treatment methods of aac have not yet been established , but it is usually determined by the patient 's condition . i believe that early cholecystectomy in this case was an effective treatment tool for avoiding potential failure of conservative management and for preventing recurrence , although the patient was young and had none of the risk factors . as mentioned above , laparoscopic appendectomy may mask clinical signs and symptoms of aac . therefore , when right upper quadrant pain , fever , leukocytosis , and abnormal liver function tests are observed after surgery , physicians should consider the possibility of aac , and promptly check radiological findings . aac arising as a complication of laparoscopic appendectomy has been reported rarely , especially in young healthy patients . when abdominal pain , leukocytosis , fever and abnormal results of liver function tests are observed in patients after appendectomy , the possibility of aac should be considered . prompt recognition and appropriate treatment of aac is necessary to minimize the associated morbidity and mortality .

acute acalculous cholecystitis ( aac ) is defined as acute inflammation of the gallbladder in the absence of gallstones . aac occurs in patients after major surgery and in the presence of serious co - morbidities such as severe trauma , burns , sepsis , prolonged intravenous hyperalimentation and hemodynamic instability . aac is rare in patients with none of the established risk factors . we present a case of a 38-year - old woman who developed aac after laparoscopic appendectomy .

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a 35-year - old woman was admitted complaining of a headache over the last two months . she had undergone a right temporal lobectomy for generalized tonic - clonic seizures 10 years earlier . laboratory tests were normal except for an increased erythrocyte sedimentation rate of 45 mm / hr . a pre - contrast ct showed a linear calcification surrounded by a lobular - shaped mass of increasing attenuation in the right frontal lobe ( fig . the mass was accompanied by extensive edema surrounding it , with a midline shifting to the left side . on mr imaging , the mass showed a heterogeneous dark signal intensity on t2-weighted images ( fig . moreover the mass had an irregular margin and was classified as an intra - axial mass with cortical involvement . three regions of interest ( roi ) were determined based on the gradient - echo echo planar imaging source images and the matching t2 and gadolinium - enhanced t1-weighted images . the roi with the highest regional cerebral blood volume ( rcbv ) was selected and was found to be almost the same as that of the contralateral side ( rcbv ratio = 1.04 ) ( fig . localized proton mr spectroscopy was performed using a multivoxel point - resolved spectroscopy sequence with an echo time of 144 msec . the spectroscopic data showed a slightly elevated choline ( cho ) and slightly decreased creatine ( cr ) and n - acetyl aspartate ( naa ) peaks with a small increase in the choline / creatine ( cho / cr ) ratio in the enhancing lesion ( fig . this diagnosis was based on the strong enhancement of the mass accompanied with severe peritumoral edema and a mass effect . however , the perfusion data and mr spectroscopy findings suggested that the mass was benign . the mass was surgically removed and the pathology revealed a foreign body - associated granulomatous inflammation with marked lymphocytic and histiocytic infiltration , microcalcification , and fibrous scar tissue formation ( fig . 1j , k ) . following surgery , the chemical agents used in neurosurgery to achieve intra - operative hemostasis can cause foreign body reactions . historically , several terms such as textiloma , gossypiboma , gauzoma , and muslinoma have been employed , reflecting the hemostatic materials involved . in our case the signal intensities of the foreign body granulomas are variable on the t1- and t2-weighted images . . variable signal intensity on t2-weighted images may reflect a complex pathology including acute or chronic inflammation , granuloma formation , fibrosis , collagen deposition , and degeneration of foreign materials . in our patient , the low signal intensity proportion of the t2-weighted images may be explained by the fibrosis seen in the histologic specimen . in the case of ring - enhancing mass lesions , these represent degenerated foreign material and may be helpful in distinguishing a muslinoma from brain abscess ( 7 ) . this was true of our patient based on the mr imaging findings showing intense mass enhancement with severe surrounding edema . however , on perfusion mri , the rcbv did not increase and , on multi - voxel mr spectroscopy , the mass cho / cr ratio increased only slightly , which was not consistent with a high - grade tumor . previous reports on perfusion and mr spectroscopic findings in patients with non - neoplastic tumor - mimicking masses showed mildly decreased - to - increased perfusion , and small rises in cho / cr ratios , with decreased naa . perfusion mri and mr spectroscopic findings from our patient were very similar to those of patients from previous reports with non - neoplastic mass lesions ( 8 , 9 ) . retrospectively , we think we could have excluded the possibility of malignancy in our patient based on the perfusion mri and mr spectroscopy , although benign tumorous conditions may not be totally excluded by such exploratory modalities . although the perfusion mri and mr spectroscopic findings are not specific for foreign body granulomas , these techniques may be helpful in excluding a high - grade tumor diagnosis , which may be the most important differential diagnosis . by combining clinical history of any previous operation , conventional mr imaging findings , and perfusion mri and mr spectroscopy , it may be possible to correctly diagnose a foreign body granuloma . in summary , conventional mri findings in foreign body granuloma patients may sometimes mimic those of brain tumors . to differentiate the diagnoses , the performing a perfusion mri and mr

we report a case of intracranial foreign body granuloma that showed features of a high grade tumor on magnetic resonance ( mr ) imaging . however , the relative cerebral blood volume was not increased in the enhancing mass on perfusion mri and the choline / creatine ratio only slightly increased on mr spectroscopy . the results suggest that the lesion is benign in nature . perfusion mri and mr spectroscopy may be helpful to differentiate a foreign body granuloma from a neoplastic condition .

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organizing pneumonia ( op ) is characterized by an indolent clinical course and a favorable prognosis although a fulminant variant has been documented . pulmonary air leak comprising pneumothorax , pneumomediastinum , and subcutaneous emphysema is rarely a presenting feature of an op . the exact pathogenesis and an appropriate management guideline have not yet been established for this dreaded complication . review of medical literature reveals only a few case reports of air leak in op . here , we report a case of op secondary to bleomycin chemotherapy , where pulmonary air leak was the major presenting symptom , which has never been reported previously . a 43-year - old female presented to our emergency department with severe shortness of breath , diffuse neck swelling , and neck pain , of 1 day duration . she had a stage iii ovarian immature teratoma diagnosed 6 months back and was treated with bilateral salpingo oophorectomy followed by 6 cycles of chemotherapy with bleomycin , etoposide , and cisplatin . one week prior to the admission , she had fever and severe cough which was treated from a local hospital . on examination , she had respiratory distress with a respiratory rate of 32/min . her spo2 was 82% in room air , blood pressure 110/70 mmhg , and heart rate 110/min . examination of the respiratory system showed equal breath sounds on both sides with bilateral fine basal crepitations and muffled heart sounds . the values for the blood gas analysis were a ph of 7.42 , pco2 of 34 mmhg , and po2 of 65 mmhg . chest x - ray showed [ figure 1 ] features suggestive of subcutaneous emphysema and mediastinal emphysema with bilateral haziness and alveolar opacities in lower zones . a computed tomography ( ct ) thorax [ figure 2 ] with findings of ground - glass opacities and peripheral consolidation , confirmed the diagnosis of pneumonia and mediastinal emphysema . mediastinal emphysema and diffuse haziness in chest x - ray ( a - c ) serial computed tomography images showing bilateral diffuse ground - glass opacities , mediastinal emphysema , and peripheral consolidation with this clinical presentation of a pulmonary air leak syndrome and radiologic picture of bilateral predominant ground glass opacities with patchy consolidations , we considered the possibility of pneumocystis jiroveci pneumonia or a drug - induced lung disease like diffuse alveolar damage / op . since the patient had severe respiratory distress and hypoxemia , she was immediately taken up for surgical management . a video - assisted thoracoscopy was done [ figure 3 ] , and the mediastinum dissected revealing multiple paracardiac blebs . these blebs were ablated ; the pneumomediastinum drained into left hemithorax , and an intercostal drainage tube was inserted in left hemithorax . video - assisted thoracoscopy showing paracardiac blebs patient 's condition improved dramatically with rising oxygen saturation . she was shifted to the intensive care unit and was treated with antibiotics , steroids , and supportive treatment . biopsy of the lung specimen [ figure 4 ] revealed bronchiolitis obliterans organizing pneumonia ( boop ) . soon the air - leak disappeared , and she was discharged from the hospital with a long - term course of steroids and macrolide . ( a ) histology showed plugs of fibrous tissue in terminal bronchioles , ( b ) trichrome stain showing fibrous proliferation op is a clinicopathologic syndrome first described by davison and epler et al . in the 1980s . causes of secondary op include infections , drugs , connective tissue diseases , organ transplantation , and inflammatory bowel diseases . the manifestations of op are nonspecific ; hence , the diagnosis is delayed in many . high index of suspicion should be kept to diagnose secondary op , especially in patients with chemotherapy , organ transplantation , etc . a unique manifestation of bleomycin toxicity is multiple pulmonary nodules in ct mimicking metastasis and having histologic characteristic of op / boop . a study conducted by mokhtari et al . found that of the 43 patients with isolated boop in cancer patients , 3 were found to be due to bleomycin . kofteridis et al . , iwanaga et al . , and yang et al . have published case reports of air leak syndrome in boop . the hallmark of op is the presence of intraalveolar buds of granulation tissue consisting of fibroblasts - myofibroblasts embedded in connective tissue . these buds may extend from one alveolus to the next through the interalveolar pores and into the bronchioles obstructing the lumen ( bronchiolitis obliterans ) . the pathogenesis proposed for air leak is that , localized plugs of fibrous tissue in the bronchiole lumen in op , produce a ball valve mechanism and alveolar over - distension , eventually leading to rupture . the air dissects through the bronchovascular sheath and ascends toward the hilum to produce a pneumomediastinum and also along the subcutaneous connective tissue to cause subcutaneous emphysema . air leakage in the mediastinum may also occur due to the rupture of paracardiac bleb . in severe interstitial lung disease ( ild ) , we also considered the possibility of pneumocystis jiroveci pneumonia and metastasis as a differential in this immunocompromised patient with fever , cough , radiologically bilateral ground glassing , and air leak , but investigation profile proved against this . in our patient , the treatment of op is long - term steroid , and the treatment for massive pneumomediastinum is limited mediastinotomy and drainage . op should be included in our differential diagnosis list , whenever a patient presents with air leak . lung biopsy should be done to confirm the diagnosis and would prove to be lifesaving as this disease responds well to steroids . limited mediastinotomy and drainage of pneumomediastinum in massive air leak is lifesaving and gives rapid improvement .

organizing pneumonia ( op ) is a less common interstitial lung disease with varying clinical picture . the development of pulmonary air leak in a case of op is an extremely rare complication . here , we report the case of a 46-year - old female with carcinoma ovary , postchemotherapy who developed respiratory distress with pneumomediastinum , and subcutaneous emphysema . lung biopsy showed evidence of op . this turned out to be a rare case of op , secondary to bleomycin chemotherapy , presenting with pulmonary air leak .

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castleman 's disease ( cd ) is a rare lymphoproliferative disorder caused by faulty immune regulation resulting in excessive b - lymphocyte and plasma - cell proliferation in lymphatic tissue . marked interfollicular vascular proliferation leads to mass formation , which can encase bronchi and sometimes cause mural erosion leading to life - threatening hemoptysis . vascular supply to these lesions have been reported to arise from the bronchial , internal mammary , and intercostal arteries . we report a case of hilar intrathoracic cd with atypical radiological features where the left inferior phrenic artery and bronchial circulation provided codominant blood supply . a 24-year - old female with a 5-month history of wheeze and nonproductive cough underwent chest x - ray , which showed a well - defined mass in the left hilar region [ figure 1a d ] . a contrast - enhanced computed tomography ( ct ) scan of the chest revealed a heterogeneously enhancing 7 5 cm mass containing flecks of calcification at the left hilum . 18 fluorodeoxyglucose positron emission tomography ( 18-fdg pet ) scan demonstrated an inhomogeneous hypermetabolic lesion with no evidence of metastatic uptake . a ct - guided percutaneous core biopsy revealed chronic inflammatory tissue with no evidence of malignancy . due to worsening cough and wheeze , the patient underwent a thoracotomy and surgical resection . during the operation there was massive blood loss of 2000 ml . histopathology confirmed the mass to have marked lymphoid infiltrate with irregular b cell follicles and hyaline vascular - like change consistent with cd . chest x - ray of a 24-year - old female ( a ) showing well - defined left hilar mass . contrast - enhanced ct scan ( b and c ) shows heterogeneously enhancing mass with coarse calcifications within this hilar mass . 18-fdg pet / ct scan ( d ) shows hypermetabolic uptake within the lesion two months after the thoracotomy , the patient presented to the emergency department with a 1-day history of massive hemoptysis ( > 200 ml ) . a ct pulmonary angiogram for clinically suspected pulmonary embolism showed no pulmonary embolism , however , multiplanar reformats showed low attenuation soft tissue in the surgical resection bed at the left hilum receiving blood supply through hypertrophied left bronchial and left inferior phrenic arteries [ figure 2a f ] . the patient had an embolization through a right common femoral artery approach and the common ( conjoined ) origin of the right broncho - superior intercostal trunk and left bronchial arteries were catheterized with a 5 fr ( cordis , usa ) left amplatz coronary i catheter ( cordis , usa ) . the sharply angulated left bronchial artery could not be superselectively catheterized with a range of microcatheters . the main trunk was embolized with 300500 micron polyvinyl alcohol ( pva ) particles ( cook , usa ) . the medial division of the inferior phrenic artery was seen to supply the mass via its pericardial branch . this was super - selectively catheterized with the same 5 fr catheter and a renegade microcatheter ( boston scientific , usa ) and embolized with the same pva particles . no spinal , esophageal , or coronary supply was demonstrated from the bronchial and left inferior phrenic arteries . there were no procedure - related complications and the patient had an uneventful recovery with no further hemoptysis during the 3 years follow - up period . contrast - enhanced ct with mip images ( a and c ) showing blood supply to the lesion with bronchial artery and left inferior phrenic artery ( arrows ) . catheter angiogram demonstrates bronchial artery ( arrow in b ) and left inferior phrenic artery ( arrow in d ) and subsequent embolization with pva ( e and f ) cd may be localized or multicentric and primarily involves the mediastinum , neck , and mesentery . there are three known histological variates namely ( a ) hyaline - vascular , ( b ) plasma - cell , and ( c ) mixed variant . classic features on a ct scan is a solitary , intensely , and homogeneously enhancing mass with no local invasion . the standard treatment of the localized form is surgical resection , however , where there is encasement or invasion of the adjacent structures , preoperative embolization has been advocated . recently , embolization alone without surgical resection has been shown to terminate hemoptysis and alleviate shortness of breath due to airway compression in patients with unresectable disease . in our patient , preoperative embolization , which may have reduced the large volume intraoperative blood loss , was not considered . it was only when the patient presented with hemoptysis after surgical resection that the vascular supply was identified and an emergency referral to interventional radiology was made . previous reports have identified bronchial , internal mammary , and intercostal arteries as feeding vessels to cd . inferior phrenic supply to cd has not been reported before to the best of our knowledge . when basal lung segments are suspected as the source of hemoptysis , inferior phrenic supply should always be considered . inferior phrenic supply to hilar masses is much rarer , but when it occurs , the supply is usually via the pericardial branch of its medial division . the left inferior phrenic medial branch may supply the esophagus , and it is important to exclude any esophageal supply before particulate embolization . careful review of multiplanar reformats of the ct scan aided procedure planning and the consent process by identifying the hypertrophied arterial feeders . cd should be considered in the differential diagnosis for all benign intrathoracic masses . where a mass shows avid enhancement , whether homogeneous or heterogeneous , a ct angiogram ,

castleman 's disease ( cd ) is a rare lympho - proliferative disorder due to faulty immune regulation resulting in proliferation of lymphatic tissue . the vascular supply to these lesions have been reported to arise from the bronchial , internal mammary and the intercostal arteries . we report a case of hemoptysis secondary to intrathoracic cd with vascular supply arising from the left inferior phrenic artery which was successfully embolised with polyvinyl alcohol ( pva ) particles .

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persistent left superior vena cava ( plsvc ) is a congenital but benign vascular anomaly with a prevalence of 0.3 - 0.5% in the general population . plsvc is one of the most common cardiovascular anomalies but is generally asymptomatic , and it is thus often identified accidentally during cardiovascular ultrasound / ct scan screening or coronary interventional angiography . anatomically , plsvc causes the aberrant backflow vein to drain into the retrograde positioned coronary sinus . some researchers have called attention to the risk of atresia of the coronary sinus among the anomalies associated with plsvc , but there are no recommendations regarding anticoagulation therapy for patients with plsvc . nevertheless , coronary sinus atresia ( csa ) due to plsvc is a rare complication . in patients with hematological malignancies , the insertion of a central venous catheter ( cvc ) is required for the patient to undergo intensive chemotherapy . hematologists must make a decision whether to conduct a cvc insertion for patients with a given complication . there are a few reports of csa in plsvc induced by central venous catheterization , pacemaker wire placement , or cardiac surgery . the placement of a cvc might evoke arrhythmia due to an additive enhancement of the patient 's arrhythmogenic condition . considering such a situation , it may not be advisable to insert a cvc in a plsvc patient with a hematological malignancy . we treated a 42-year - old male with stage iv hodgkin 's lymphoma with bone marrow involvement . the initial chemotherapy ( abvd , doxorubicin 25 mg / m , bleomycin 9 mg / m , vinblastine 6 mg / m , and dacarbazine 250 mg / m , day 1 and 15 ) was effective , resulting in complete remission after 6 cycles of abvd . although the abvd chemotherapy had been administered via a peripheral vein , salvage chemotherapy was initiated via an implantable venous access port catheter because his peripheral blood accesses were ultimately unusable . he received an indwelling port catheter from the left subclavian vein , since the right subclavian approach was not possible . 1a ) , which was found at the time for the first time in his life . the patient successfully completed a total of 3 courses of salvage chemotherapy constructed with arac , carboplatin , etoposide , and methylpredonisolone ( aces ) . although obstruction of the coronary venous drainage caused by plsvc has been suggested , it is not always thrombogenic . a small plsvc flow can easily connect to hemostasis of the venous circulation return . in our patient , the plsvc cavity had enough space for a port catheter to be cannulated and positioned ( fig . . ideally the back flow and diameter of the plsvc to the coronary sinus should be evaluated by cardiovascular ultrasound or cardiography . although plsvc is a rare congenital anomaly , some risks including thrombosis and occlusion should be annotated when the patient receives a cvc insertion . the relationship between csa and plsvc remains unclear ; however , the hematologist should pay attention to the malpositioning of the cvc tip . informed consent to participate in the study was obtained from the participant . written informed consent was obtained from the patient for publication of this case series and any accompanying images . a copy of the written consent is available for review by the editor - in - chief of this journal .

persistent left superior vena cava is a congenital vascular anomaly , which is possibly arrhythmogenic and thrombogenic , rarely complicated with coronary sinus atresia . we treated a 42-year - old male with hodgkin 's lymphoma requiring central venous catheter placement for intensive chemotherapy . persistent left superior vena cava was revealed after the insertion of the central venous catheter by the radiological finding of the catheter tip cannulated into the vena cava cavity . the relationship between coronary sinus atresia and persistent left superior vena cava induced by central venous catheterization remains unclear ; however , the hematologist should pay attention to the malpositioning of the central venous catheter .

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to fabricate the vertical wse2/mos2 heterojunction devices , wse2 was grown using a physical vapor deposition process on a si / sio2 ( 300 nm sio2 ) substrate . a total of 0.2 g wse2 powder ( alfa aesar , 13084 ) was added into an alumina boat as precursor . the blank si / sio2 substrates ( 1 cm 5 cm ) were loaded into a home - built vapor deposition system in a horizontal tube furnace ( lindberg / blue m ) with 1 in . the system was pumped down to a vacuum of 10 mtorr in 10 min , and refilled with 150 sccm of ultrahigh purity argon gas ( airgas , 99.9999% ) then heated to desired growth temperature within 30 min . after that , the growth kept at the desired temperature for 30 min , and then terminated by shutting off the power of the furnace . the mos2 flakes were then exfoliated onto the wse2 flakes through a micromechanical cleavage approach . the metal electrodes ( for probe contact or wire bonding purposes ) were patterned on the si / sio2 substrates by using electron - beam lithography and electron - beam deposition of ti / au ( 50/50 nm ) thin film . ni / au ( 5/50 nm ) contact electrodes were then deposited to form the ohmic contact to mos2 and au ( 50 nm ) was deposited to form the ohmic contact to wse2 . the microstructures and morphologies of the nanostructures are characterized by a jeol 6700 scanning electron microscope ( sem ) . the cross - sectional image of the heterostructure device is obtained by an fei titan transmission electron microscope ( tem ) . the dc electrical transport measurements were conducted with a lakeshore probe station ( model ttp4 ) and a computer - controlled analogue - to - digital converter ( national instruments model 6030e ) . the confocal micro - pl and raman measurements were conducted on a horiba labhr confocal raman system with 600 g / mm grating , 50 diffraction - limited objective ( n.a . = 0.75 ) , with an ar laser ( 514 nm ) or a he ne laser ( 633 nm ) excitation . the scanning photocurrent measurements were conducted with the same horiba labhr confocal raman system combined with the same electrical measurement system . the el measurements were performed on a home - built confocal pl measurement system combining with the same electrical measurement system with a temperature control in ar environment . unless mentioned in the main text , all measurements were conducted at room temperature . = 0.5 ) and captured by a liquid - nitrogen - cooled ccd camera ( princeton instruments pylon 400f ) . the spectra were taken by using an acton 2300i spectrometer with 150 g / mm grating and liquid - nitrogen - cooled ccd .

the p n diodes represent the most fundamental device building blocks for diverse optoelectronic functions , but are difficult to achieve in atomically thin transition metal dichalcogenides ( tmds ) due to the challenges in selectively doping them into p- or n - type semiconductors . here , we demonstrate that an atomically thin and sharp heterojunction p n diode can be created by vertically stacking p - type monolayer tungsten diselenide ( wse2 ) and n - type few - layer molybdenum disulfide ( mos2 ) . electrical measurements of the vertically staked wse2/mos2 heterojunctions reveal excellent current rectification behavior with an ideality factor of 1.2 . photocurrent mapping shows rapid photoresponse over the entire overlapping region with a highest external quantum efficiency up to 12% . electroluminescence studies show prominent band edge excitonic emission and strikingly enhanced hot - electron luminescence . a systematic investigation shows distinct layer - number dependent emission characteristics and reveals important insight about the origin of hot - electron luminescence and the nature of electron orbital interaction in tmds . we believe that these atomically thin heterojunction p n diodes represent an interesting system for probing the fundamental electro - optical properties in tmds and can open up a new pathway to novel optoelectronic devices such as atomically thin photodetectors , photovoltaics , as well as spin- and valley - polarized light emitting diodes , on - chip lasers .

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fried seeds subjected to grinding by adding sufficient water to it for 30 - 45 min . the mixture was filtered through muslin cloth and pea nut milk is separated . solvent { ethanol : acetone ( 1:1 ) } was added to the milk and then subjected to refrigeration for 30 min . indomethacin was dissolved in chloroform and bio - polymer solution was prepared by adding water to it . the drug solution was added to bio - material solution and mixed by magnetic stirrer until emulsion is formed . release of drug through egg shell membrane : egg shell membrane was separated using con . the egg shell membrane attached to the tube . measured quantity of micro particles 5 ml solution was withdrawal and 5 ml buffer solution was added to make the volume . same procedure was repeated for different formulated films of aceclofenac with phosphate buffer ( ph-7.4 ) . the dissolution studies were perform and subjecting it for dissolution for 3 hrs and analyze the samples by uv spectrophotometer at 320 nm . % cummulative release vs time in ph 1.2 % cummulative release vs time in ph 7.4 fried seeds subjected to grinding by adding sufficient water to it for 30 - 45 min . the mixture was filtered through muslin cloth and pea nut milk is separated . solvent { ethanol : acetone ( 1:1 ) } was added to the milk and then subjected to refrigeration for 30 min . indomethacin was dissolved in chloroform and bio - polymer solution was prepared by adding water to it . the drug solution was added to bio - material solution and mixed by magnetic stirrer until emulsion is formed . release of drug through egg shell membrane : egg shell membrane was separated using con . the egg shell membrane attached to the tube . measured quantity of micro particles 5 ml solution was withdrawal and 5 ml buffer solution was added to make the volume . same procedure was repeated for different formulated films of aceclofenac with phosphate buffer ( ph-7.4 ) . the dissolution studies were perform and subjecting it for dissolution for 3 hrs and analyze the samples by uv spectrophotometer at 320 nm . % cummulative release vs time in ph 1.2 % cummulative release vs time in ph 7.4 five different formulations were formulated using various proportion of bio loaded sustained release bio - micro particles was performed . it had t50% and t 80% of 1.56 hrs and 2.45 hr formulation fg-5 shows percentage yield t50% and t80% of 1.62 hrs and 2.61 hrs at hence these two formulations are the best among the five prepared formulations .

indomethacin microparticles prepared by extraction of bio polymer from arachis hypogen . in vitro drug release study was carried out through egg shell membrane for 3 hrs and analyzed sample by uv spectroscopy at 320 nm . a novel bio membrane from arachis hypogen was isolated by simplify economical process . the % yield was found to be 80% and particle range was 3265 m .

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a 36-year - old japanese man was referred to us for the evaluation of bilateral retinal hemorrhages . he developed an acute vision decrease in his left eye , pain in his right chest area , and headache after he had trekked at an altitude of 4600 m in tibet for 1 week . because of the illness , he descended 3 days later , and he felt better at that time but the visual impairment remained . our examination showed that his visual acuity was 20/20 od and 20/200 os with refractive errors of 0.25 diopters ( d ) od and 0.50 d os measured 3 weeks after the onset of the visual decrease . funduscopic examination revealed multiple intraretinal hemorrhages bilaterally and a macular hemorrhage in the left eye [ fig . 1 ] . sd - oct ( spectralis , heidelberg engineering , heidelberg , germany ) showed that the macular hemorrhage was in the superficial layer of the retina beneath the inner limiting membrane of the left eye [ fig the thickness of the choroidal layer at the fovea was 530 m od and 490 m os which was thicker than the mean subfoveal choroidal thickness in normal subjects of approximately 300 m in the enhanced depth images obtained by spectralis sd - oct . most recent studies report that the average subfoveal choroidal thickness is 287 m in caucasians of an average age of 50.4 years and 272.6 m in the japanese of an average age of 30.5 years obtained by the enhanced depth imaging of the spectralis sd - oct . fundus photograph of the right eye ( a ) and the left eye ( b ) showing multiple intraretinal hemorrhages and a macular hemorrhage in the left eye optical coherence tomographic images at the first visit . the choroidal layers ( white arrowheads ) are thick in both eyes ( a : right eye , b : left eye ) . a macular hemorrhage located in the superficial retina beneath the inner limiting membrane of the left eye ( white arrow ) can be seen individuals with acute mountain sickness present with lethargy , nausea , headache , insomnia , anorexia , and disorientation . the proposed mechanism for the symptoms of acute mountain sickness is respiratory alkalosis from hyperventilation and increased cerebral blood flow . in hace , there is a breakdown of the blood however , hace can lead to long - lasting severe neurological and psychiatric disorders and even death in some cases . wiedman and tabin examined 40 climbers who had ascended to altitudes of over 4870 m whether they developed signs of har , symptoms of acute mountain sickness , and clinically signs of hace . thus , they concluded that when advanced har is recognized , treatment should be initiated for hace with oxygen , steroids , or diuretics , and immediate descent to prevent further progression of hace . a pronounced increase in retinal blood flow in mountaineers with retinal hemorrhage and dilated epipapillary network has been detected with heidelberg retina flowmeter after acute hypoxic stress at high altitudes . the increase in retinal blood blow and cerebral blood flow under hypoxic conditions may also be associated with an increase in choroidal blood flow resulting in an increase in choroidal thickness . the pathogenesis of the increased choroidal thickness may be similar to that of hace , namely a breakdown of the blood it is difficult to draw strong conclusions from a single case ; however , we suggest that measurements of the choroidal thickness may be useful in evaluating the status of hace . currently , data are not available from population - based studies on the normal values for the choroidal thickness of a large number of caucasians or asians . further studies are needed to evaluate the choroidal thickness in mountaineers with acute mountain sickness .

we report a case of high - altitude retinopathy with increased choroidal thickness detected by spectral - domain optical coherence tomography ( sd - oct ) . a 36-year - old japanese man developed an acute vision decrease in his left eye after he had trekked at an altitude of 4600 m in tibet for 1 week . his visual acuity was 20/20 od and 20/200 os with refractive errors of 0.25 diopters ( d ) od and 0.50 d os 3 weeks after the onset of the visual decrease . funduscopic examinations revealed multiple intraretinal hemorrhages bilaterally and a macular hemorrhage in the left eye . sd - oct showed that the thickness of choroidal layer at the fovea was 530 m od and 490 m os which is thicker than that in normal subjects of approximately 300 m . we suggest that the increase in the retinal blood flow under hypoxic conditions may be associated with an increase in the choroidal blood flow resulting in an increase in choroidal thickness .

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from msm who attended the amsterdam municipal health service sti outpatient clinic in 2000 and 2001 , randomly selected stored specimens of c. trachomatis dna positive ( as assessed by ligase chain reaction , abbott laboratories , chicago , il , usa ) rectal samples were tested for the c. trachomatis variant by real - time pcr ( 6 ) . from 2002 to 2005 , msm with symptomatic proctitis ( i.e. , purulent discharge , rectal ulceration , bleeding , or edematous mucosa ) and msm without symptoms were included . from the san francisco region , 51 lgv positive isolates from symptomatic msm were analyzed ( 7 ) . the isolates were collected in medical clinics ( e.g. , ambulatory care , emergency room , screening , acute care ) from 1979 to 1985 ( table ) . lgv was assessed at the time of collection , according to phenotypic properties observed during cell culture . although the growth characteristics of lgv serovars can be distinguished from serovars d k , cell culture for c. trachomatis is no longer available in most clinical settings . * in 2002 and 2003 , 45 lgv l2b variants of 109 isolates have been described in detail ( 5 ) . c. trachomatis serovar typing was performed as described previously ( 5 ) . briefly , amplification of the ompa gene ( 1.1 kb ) was performed in a nested pcr format . the ompa nucleotide sequences were subsequently analyzed by automated dna sequencing on an abi 310 sequencer ( pe biosystems , foster city , ca , usa ) . the sequences obtained from c. trachomatis infected msm in 2000 and 2001 in amsterdam and from msm in san francisco were compared to the recently identified l2b variant to determine if the strain was present earlier . the table presents the results of this analysis . in the amsterdam c. trachomatis dna positive rectal samples , lgv strains were detected by real - time pcr in 2 of 67 samples in 2000 and in 4 of 28 samples in 2001 . sequencing showed that in all 6 lgv strain positive samples , the l2b variant was present . also in 2002 and 2003 , 109 l2b - positive samples of 403 c. trachomatis dna positive rectal samples were identified , of which 45 were strain l2b , and these have been described in a previous publication ( 5 ) . all 51 san francisco specimens ( from 51 patients ) were positive for lgv variants by real - time pcr . by sequencing variable segment 2 of the ompa gene ( vs-2 ) , we identified 15 as serovar l1 , 18 as serovar l2 prototype , and 18 as the l2b variant . we sequenced the complete ompa gene of 5 of these 18 l2b variants that originated in san francisco ; all were identical to the recently described l2b variant circulating in amsterdam . four nucleotide changes were found when compared to reference serovars l2 , l2a , and the variant l2 , including 1 change that encoded the previously undescribed change at amino acid 162 , aatagt ( 5 ) . the l2b lgv variant identified as the cause of all the lgv proctitis in the recent outbreak among msm in amsterdam appears to have been circulating in amsterdam in 2000 . moreover , we showed that this l2b variant was present in the 1980s in san francisco with exactly the same mutations in the complete ompa gene . however , since we only sequenced the ompa gene , and although the sequence was identical in old and new l2b strains , we can not exclude the possibility that it could involve different strains of c. trachomatis that differ in other parts of the genome , although this is unlikely . since lgv causes potentially severe infections with possibly irreversible sequelae if adequate treatment is not begun promptly , early and accurate diagnosis is essential . sequence - based nucleic - acid tests that can discriminate between lgv serovars and less invasive c. trachomatis species can help detect cases and prevent further transmission of lgv . in conclusion , our results suggest that we are dealing with the same lgv variant > 25 years later , and the current lgv outbreak in industrialized countries has most likely been a slowly evolving epidemic with an organism that has gone unnoticed in the community for many years and is now being detected by new technologies . the numbers detected in 2005 in amsterdam suggest that a considerable reservoir exists , which emphasizes the need for ongoing public health awareness .

we traced the chlamydia trachomatis l2b variant in amsterdam and san francisco . all recent lymphogranuloma venereum cases in amsterdam were caused by the l2b variant . this variant was also present in the 1980s in san francisco . thus , the current " outbreak " is most likely a slowly evolving epidemic .

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primary chest wall chondrosarcoma is a relatively rare malignant tumor [ 1 , 2 , 3 ] . when a patient with a history of long - term asbestos exposure has a pleural tumor with multiple plaques on chest computed tomography ( ct ) , malignant pleural mesothelioma is usually suspected . a 62-year - old man with a history of long - term asbestos exposure as a construction worker was found to have a chest wall tumor on chest ct and referred to our hospital . chest ct showed a pleural tumor invading the sixth rib and multiple pleural plaques ( fig . additional wide resection of the chest wall was performed , that is , en bloc resection , including the fifth , sixth , and seventh ribs , with a 5-cm safety margin from the tumor along the sixth rib . the chest wall defect was 25 10 cm in size , and chest wall reconstruction was performed with a polypropylene mesh . microscopic examination revealed a lobulated growth pattern of cartilaginous cells of histological grade 1 ( fig . although the margins are free of tumor cells , the tumor widely spread into the sixth rib , to 17 cm long . chest wall chondrosarcoma is relatively rare [ 1 , 2 , 3 ] . to the best of our knowledge , this is the first reported case of chondrosarcoma of the rib mimicking malignant pleural mesothelioma . two cases of extraskeletal mesenchymal chondrosarcoma mimicking malignant pleural mesothelioma have been reported [ 4 , 5 ] . goetz et al . reported a case of myxoid chondrosarcoma with a history of asbestos exposure . in our case , the patient had a history of long - term asbestos exposure and multiple pleural plaques on chest ct . additionally , diagnosis of malignant pleural mesothelioma by using fnac is insufficient because it can not differentiate malignant pleural mesothelioma from adenocarcinoma . chondrosarcoma is relatively radio insensitive , and no effective chemotherapy has been established so far . thus , complete surgical resection is the only curative option for chondrosarcoma [ 1 , 2 ] . reported that local recurrence rate was highly dependent on surgical margins . therefore , wide resection with adequate safety margin is recommended . in our case , the tumor appeared as small as 3 cm on chest ct , but the tumor cells widely spread into the sixth rib , to 17 cm long . because it is difficult to diagnose the free margin of the rib in intraoperative frozen sections , preoperative planning for wide resection of the chest wall is important . chest wall reconstruction is recommended when at least three ribs are resected or when the resected size of the chest wall defect is more than 10 cm in order to avoid pulmonary complications . our case suggests that it is difficult to diagnose chondrosarcoma in preoperative imaging diagnosis , and wide resection is necessary for curative treatment .

a 62-year - old man with a history of long - term asbestos exposure was found to have a chest wall tumor invading the sixth rib on chest computed tomography . the computed tomography also revealed multiple plaques in the pleura . malignant pleural mesothelioma was suspected , and thoracoscopic surgery was performed . thoracoscopy revealed that the tumor location was extrapleural . thus , excisional biopsy was performed . the tumor was histologically diagnosed as chondrosarcoma . additional wide resection of the chest wall , including the fifth , sixth , and seventh ribs , was performed . chest wall reconstruction was performed with a polypropylene mesh .

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cadaver renal transplantation is fast becoming an important modality in the management of end - stage renal disease ( esrd ) , in india . in the present scenario it is imperative that we improve the donor pool , such that more chronic kidney disease patients are benefited . the existing renal malignancy is a contraindication for renal transplantation , but data regarding graft kidneys with suspicious solid renal masses are not widely available . a 50-year - old man with a history of road traffic accident ( rta ) was admitted to intensive care unit ( icu ) and declared brain dead . formal consent for organ donation was obtained from the relatives and organ harvesting was done . under the organ sharing network , our institution received the left kidney . a 36-year - old , same blood group , routine evaluation of the recipient was done . during bench dissection of the donor kidney , a 1.5 2 c - arm screening was done and no radio opaque lesion was seen . as the cadaver transplantation was done in odd hours , frozen section facilities were not available . as the lesion was found in the mid zone of the graft kidney , partial nephrectomy was not attempted and we proceeded with enucleation of the solid lesion . the nephrotomy wound was closed with absorbable sutures and the kidney was grafted to the recipient [ figure 1 ] . post - operative recovery was uneventful and urine output improved to 150 - 200 ml / day from post operative day two . donor autopsy was done and no evidence of any other malignant lesions or lesions suggestive of metastasis was found . renomedullary interstitial cell tumour , a benign lesion of the renal medulla [ figure 2 ] . renal imaging with a plain ct scan done two months postoperatively , found no lesion in the kidney . although the number of live and cadaver renal transplants have increased in recent years , there continues to be a significant deficit . the increase in the donor pool is not able to match the ever increasing population with esrd and many patients die each year waiting for a suitable graft . the presence of malignancy in a renal graft is considered to be a contraindication to renal transplantation . there are many studies that have studied the use of kidneys with incidental detected renal masses in renal transplantation . our decision in this case to go ahead with the transplantation of the graft after enucleation was due to the small size of the lesion , its grossly benign appearance , and to give the recipient a better chance of survival and quality of life . in july 2009 , reported a series of five cases where < 2.3 cm incidental renal masses were subjected to back table partial nephrectomy and transplanted into the matched recipients . there was no evidence of cancer - specific mortality or recurrence at a 15-month follow - up . mchayleh et al . , in 2008 , reported two cases of metastasis from renal cell carcinoma in a kidney allograft . hence , many articles have been published regarding the use of grafts with renal malignancies . however , data on the management of benign renal masses in donor kidneys are few . renomedullary interstitial cell tumour is a common autopsy finding in patients over 50 years , being found in about 30% of this group . these lesions are usually round to oval , pale gray to yellow with a mean size of 3 mm . clinically symptomatic tumours are rare . the term renomedullary interstitial cell tumour was coined by lerman et al . , in 1972 . the previous terminology used was renal medullary fibroma. the finding of a discrete renal mass during bench dissection for a cadaveric renal transplant raises many questions . forty to fifty percent of renal masses less than 2 cm in size are benign . meticulous back table dissection and subsequent histopathological confirmation are necessary when such kidneys are transplanted . hence , such transplant recipients should be diligently followed up to look for recurrence of renal masses and also for occurrence of metastasis . this situation also brings up the case of the need for imaging studies like a contrast - enhanced ct , for the evaluation of potential cadaveric donors . in some cases , it may not be possible to shift the brain dead donor with all supports to the ct room . hence , at least a bedside ultrasound may add to our preoperative assessment of the kidney . incidentalomas like in our case could have been picked up on imaging and the surgical team was better prepared to deal with the situation . therefore , routine imaging studies like the ct or ultrasound may be advocated for all potential cadaveric donors , preoperatively . the increase in the use of imaging studies for a variety of abdominal conditions has increased the rate of detection of small clinically insignificant renal masses .

the number of patients living with end - stage renal disease ( esrd ) is increasing in our country and demand for renal grafts is ever increasing . cadaver renal transplantation is being established as a viable supplement to live transplantation . we present a case where a mass lesion was encountered in the donor kidney from a cadaver . enucleation of the lesion was done and we proceeded with the grafting . histopathological examination showed a renomedullary interstitial cell tumour , a rare benign lesion . post transplant , the renal function recovered well and the patient is asymptomatic . such incidental renal masses present an ethical dilemma to the operating surgeon .

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morgagni hernia is a congenital herniation of abdominal viscera into the thoracic cavity through a retrosternal diaphragmatic defect . it could be an incidental diagnosis in adulthood or could present with obstructive symptoms from the herniated viscera . surgical treatment consists of direct closure or mesh placement for the diaphragmatic defect , or suturing by transabdominal or transthoracic access . we report a patient with morgagni hernia who underwent a laparoscopic mesh placement with reduced port surgery ( rps ) . an 85-year - old female presented in er with a 2-day history of upper abdominal discomfort and loss of appetite . she had never experienced the same symptoms previously , and she denied any history of abdominal trauma . physical examination revealed no palpable mass in the upper abdomen , and local tenderness on upper abdomen was shown without any peritoneal inflammatory signs . serum blood test showed a hyperlipidemia and mild elevation of urea nitrogen ( total cholesterol , 250 mg / dl ; urea nitrogen , 22.5 mg / dl ) . a ct scan showed a huge diaphragmatic anterior hernia with a segment of transverse colon and fat tissue migration ( fig . the diagnosis of morgagni hernia was made and the patient was considered for repair of the diaphragmatic defect by the laparoscopic approach . under general anesthesia in the lithotomy position , the sils port ( covidien , tokyo , japan ) was inserted into a 2.5-cm umbilical incision vertically . after inspection of the visceral space , a second port , 12 mm in size , was inserted into the left lower abdomen . the herniated bowel and fat tissues were gently pulled down with grasping forceps and placed entirely into the abdominal cavity ( fig . the defect was ovoid and approximately 5 cm in size , and difficult to close by the suturing technique ; therefore we performed mesh placement with gore - tex dual mesh ( gore inc . operation time and operative blood loss were 157 min and 5 ml , respectively . the patient started to eat a soft meal on day 1 after surgery and was discharged from our hospital on day 8 after surgery without any symptoms . after 6-month , 12-month , and 24-month follow - ups , the patient had no sign of recurrence of the morgagni hernia ( figs . 4 and 5 ) . giovanni - battista morgagni first described this type of hernia in 1769 . at present , it could be an incidental diagnosis in adulthood or could present with obstructive symptoms of the herniated viscera . surgical treatment is required to relive current symptoms or to prevent possible future complications such as strangulation ileus or incarceration . originally , direct closure of the hernia site or mesh placement was used as the surgical options by laparotomy or thoracotomy . recently , the laparoscopic procedure has become available to treat this type of hernia and has bought a number of advantages such as reduced pain , shorter recovery time , and cosmetic benefits . in addition , recent trends in laparoscopic procedures have been toward minimizing the number of incisions to achieve less invasiveness . examples of such approaches are single incision laparoscopic surgery ( sils ) and reduced port surgery ( rps ) . only one report previously described morgagni hernia repair using single port access and closing the hernia site by non - absorbable suturing into extra - abdominal region . this report was very successful , however postoperative pain might be occurred because of suturing tension by lifting the interrupted sutures to close the hernia site . some technical problems associated with sils have been reported : restriction of the working field and interference of surgical instrument . the sils technique does not rely on triangulation , which is one of the core principles of conventional laparoscopic surgery , allowing adequate operative exposure while maintaining an ergonomic position for the surgeon and assistant . consequently , the inherent technical challenge that arises from the sils technique is that of a compromised view and locomotive field . therefore unfavorite outcomes such as longer operative time and possibly higher complication rate have been reported in early period of sils operation . a small additional port or a reduced number of ports as with rps are modifications that may overcome these problems . in combination with the sils port and the additional port enable the performance of dual - port surgery , even for complex operation such as laparoscopic gastrectomy . this type of repair is technically easy and should have a high probability of success because of the tension free condition . also , less postoperative pain is also expected , compared to the external knot tying technique . thoracoscopic approach is also other option for this type of hernia as a less invasive treatment , although the benefits over conventional laparoscopic approach have not been cleared . although the benefits of sils or rps over conventional laparoscopic surgery have not been established , either sils or rps could be the first choice for symptomatic morgagni hernia repair because of the acceptable operation time , blood loss , and clinical outcome . basically , cosmetic benefits and less operative pain are also expected as advantages of sils or rps originating from fewer incisions . in addition , tissue trauma and port - related complications such as organ damage , adhesions , bleeding , wound infections and hernias could be decreased . for the future direction , additional this approach is safe and can be the good indication for this kind of hernia . written informed consent was obtained from the patient for publication of this case report and accompanying images .

highlightsmorgagni hernia is a rare diaphragmatic hernia and standard therapy has not been established.the laparoscopic repair of a rare diaphragmatic morgagni hernia in an elder patient using the reduced port approach is described.this reduced port approach is a good indication for this type of hernia because of less invasive ness , cosmetics and safety .

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a 75-year - old man with a slightly increased serum creatinine level had developed proteinuria and hypertension in 2000 . in 2007 , he noticed a gradually progressive hearing loss and repeated bloody nasal discharge resulting from a refractory sinusitis . initial laboratory findings revealed elevated serine proteinase 3-anti - neutrophil cytoplasmic antibody ( pr3-anca ; 26.2 eu ) , blood urea nitrogen ( 35 mg / dl ) , and serum creatinine ( 1.62 mg / dl ) levels . because of these combined findings , he was diagnosed as having granulomatosis with polyangiitis ( gpa ) according to the american college of rheumatology 1990 criteria for gpa and watts algorithm [ 1 , 2 ] . the birmingham vasculitis activity score 2003 was 6 . because of the low disease activity , the slow progression and the advanced age , we did not initiate immunosuppressive therapy at this time . in october 2008 , he developed fever lasting for several days . laboratory data were as follows : c - reactive protein 11.91 mg / dl , pr3-anca 49.1 u / ml , fibrinogen 752 mg / dl , d - dimer 1.7 g / ml , and urinary protein 0.27 g / day . activated partial thromboplastin time , prothrombin time and fibrin degradation product were within the respective normal range . although we administered meropenem ( 2.0 g / day for 1 week ) , vancomycin ( 500 mg / day for 17 days ) and itraconazole ( 200 mg / day for 20 days ) , the fever and c - reactive protein level did not decrease . on day 12 of admission a brain mri revealed a mass lesion in the right frontal lobe and hypertrophic mucosa in the paranasal sinuses ( fig . 1a ) in addition to a thickened and strongly enhanced dura mater surrounding the mass lesion ( fig . however , he rapidly developed left hemiparesis and deterioration of consciousness [ glasgow coma scale ( gcs ) : e1v2m4 ] . a brain ct revealed that the parenchymal mass lesion had enlarged and the mucous effusion was invading the posterior wall of the right frontal sinus . due to an impending transtentorial herniation , a decompressive hemicraniectomy and partial right frontal lobectomy were performed , which moderately improved his consciousness ( gcs : e2v3m4 ) . after the surgery , he developed bloody sputa , and a chest ct revealed an infiltrative shadow in both lungs . the biopsied brain material from the surgery revealed a granulomatous inflammation with geographic necrosis and multinucleated giant cells in the perivascular area of the thickened dura mater and leptomeninges ( fig . small vessels in the meninges were involved in the granulomatous lesions , and the lumens of the veins were often occluded . in the cerebral cortices and the white matter in these areas , hemorrhagic infarction was widely observed . after treatment with prednisolone ( 20 mg / day ) and azathioprine ( 40 mg / day ) , the disturbance of consciousness substantially improved ( gcs : e4v3m5 ) , and the epistaxis stopped . this study was conducted with the approval of the ethics committee of niigata university graduate school of medical and dental sciences . cns involvement such as pachymeningitis and cerebrovascular events is uncommon in gpa , reported in only 28% of cases [ 3 , 4 ] . we previously clarified that leptomeningeal and parenchymal involvement in the brain were significantly more common in pr3-anca - positive hypertrophic pachymeningitis compared to myeloperoxidase anti - neutrophil cytoplasmic antibody - positive and idiopathic hypertrophic pachymeningitis in a study of 36 patients ( including this case ) . based on the study , mri findings showed an enhancement of both the pachymeninges and leptomeninges . moreover , the present case had the extension of the mass lesion with the granulomatous inflammation , and the venous obstruction resulted in severe edema and hemorrhagic infarction . emergency decompressive craniectomy and partial lobectomy for cerebral infarction with gpa likely contributed to our patient 's survival . to our knowledge , this is the first report successfully managed with surgical decompressive craniectomy .

central nervous system ( cns ) involvement , such as pachymeningitis and/or cerebrovascular events , is rare in patients with granulomatosis with polyangiitis ( gpa ) . furthermore , the details of pathological examinations of cases have rarely been described . we describe a case of gpa that manifested as an isolated paranasal sinus disease that invaded the subarachnoid space and caused a hemorrhagic venous infarction . we also describe the pathological characteristics of the biopsied brain material from the successful decompressive craniectomy . in particular , granulomatous inflammation with geographic necrosis and multinucleated giant cells were observed in the perivascular area of the thickened dura mater and leptomeninges . small vessels in the meninges were involved in the granulomatous lesions , and the lumens of the veins were often occluded . in the cerebral cortices and white matter in these areas , hemorrhagic infarction was widely observed . we suggest that our findings represent a novel mechanism of cns involvement in gpa . moreover , we believe that the emergency decompressive craniectomy and partial lobectomy for the cerebral infarction in this patient with gpa likely contributed to his survival .

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for large scale global analysis , hela s3 cells were prefractionated using custom 2d - le platform , comprised of sief coupled to multiplexed gelfree . hela s3 , h1299 , b16f10 cells , and mitochondrial membrane proteins were also fractionated using the custom gelfree device alone ( no sief ) . after separation , detergent and salt were removed , and the fractions were injected into nanocapillary rplc columns for elution into a 12 tesla ltq ftms for online detection and fragmentation . the ms raw files were processed with in - house software called crawler to assign masses . using this program , determination of both the intact masses and the corresponding fragment masses were performed and these data were searched against a human proteome database . extensive statistical workups were also performed using several fdr estimation approaches ( with decoy databases both concatenated and not ) . a final q - value procedure is described in detail ( methods ) , with the data above reported using a 5% instantaneous fdr ( i.e. , q - value ) cutoff at the protein level ( supplementary fig .

a full description of the human proteome relies on the challenging task of detecting mature and changing forms of protein molecules in the body . large scale proteome analysis1 has routinely involved digesting intact proteins followed by inferred protein identification using mass spectrometry ( ms)2 . this bottom up process affords a high number of identifications ( not always unique to a single gene ) . however , complications arise from incomplete or ambiguous2 characterization of alternative splice forms , diverse modifications ( e.g. , acetylation and methylation ) , and endogenous protein cleavages , especially when combinations of these create complex patterns of intact protein isoforms and species3 . top down interrogation of whole proteins can overcome these problems for individual proteins4,5 , but has not been achieved on a proteome scale due to the lack of intact protein fractionation methods that are well integrated with tandem ms . here we show , using a new four dimensional ( 4d ) separation system , identification of 1,043 gene products from human cells that are dispersed into > 3,000 protein species created by post - translational modification , rna splicing , and proteolysis . the overall system produced > 20-fold increases in both separation power and proteome coverage , enabling the identification of proteins up to 105 kilodaltons and those with up to 11 transmembrane helices . many previously undetected isoforms of endogenous human proteins were mapped , including changes in multiply - modified species in response to accelerated cellular aging ( senescence ) induced by dna damage . integrated with the latest version of the swiss - prot database6 , the data provide precise correlations to individual genes and proof - of - concept for large scale interrogation of whole protein molecules . the technology promises to improve the link between proteomics data and complex phenotypes in basic biology and disease research7 .

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molecular diagnostics of cancer predisposition is very important for the medical treatment of the patient and persons belonging to the high risk group . molecular studies enable the detection of mutation carriers and release from unreasonable stress of persons from the group with increased risk of cancer occurrence . the mutation spectrums in the genes predisposing to colorectal cancer in the polish population have been described [ 1 - 4 ] . in the present work we focused on recurrent mutations of the apc gene causing fap . familial adenomatous polyposis ( fap ) is characterized by the appearance of numerous polyps in the large intestine . the correlation between mutations of the apc gene and the occurrence of familial adenomatous polyposis was described in 1991 and since then , mutations of the apc gene have been investigated in research centres leading to identification of various mutation types . mutations of the apc gene , in most cases , are small deletions or insertions with the most frequent mutations , in the greater part of the described populations , being the aaaga deletion at codon 1309 and the acaaa deletion at codon 1061 . clinical diagnoses of fap patients were conducted in collaborating genetic centres or gastroenterology clinics in the place of residence of patients . so far , samples of dna belonging to 280 polish fap families have been collected in the dna bank of polish fap families established in 1997 at the institute of human genetics , polish academy of science in poznan . dna was extracted from peripheral blood cells by the classical phenol purification method and entire coding sequence of apc gene was screened for mutations by pcr - hd and sscp methods in 280 probands . dna fragments showing heteroduplex or additional pattern in sscp analysis were sequenced by direct pcr product sequencing and analyzed using a megabace 500 sequencer according to the manufacturer 's specifications . we identified 72 mutations in 124 of our 280 fap families and observed eight types of recurrent mutations . the mutations and age of onset two of them were localized in exon 11 and the remaining six in the 3 ' part of exon 15 . the most frequent mutation , 39273931delaaaga , occurred in twenty - eight families ( 10% ) ; the second one was 31833187delacaaa , occurring in eight families ( 2.8% ) ; and the third most frequent mutation was 32023205deltcaa , detected in 5 families ( 1.7% ) . in our fap patients y500x occurred in four families ( 1.4% ) while q978x was detected in three families . each of the remaining four types of mutation occurred in two families and the frequencies of these mutations were below one percent . fifty - four recurrent mutations identified in apc gene and age of onset in a group of 124 diagnosed polish fap families nd no data available in the human mutations database at the institute of medical genetics in cardiff , considered the most representative population in the world , seven hundred mutations are listed for the apc gene . the mutation reports describe the frequency of this mutation from 0% in northwest spain , 2.4% in the australian population , 5% in dutch , 7% in israeli to 16% in the group of italian fap patients [ 6 - 9 ] . the second most frequent mutation , 31833187delacaaa , is reported with frequency ranging from 0% in northwest spain , 1.5% in israeli populations to 8.4% in australia [ 6 - 9 ] . a study of over 100 dutch families revealed equal frequency of those two most frequent mutations ( 39273931delaaaga and 31833187delacaaa ) . the latest published report in 2005 involved the analysis of over 1000 patients . in comparison to this study , the representative study of mutation frequency in the neighbouring population indicated two times higher frequency of 39273931delaaaga , whereas a difference in frequency of 31833187del - acaaa was not observed ( germany 3.8% , poland 2.7% ) . the frequency of 32023205deltcaa was equal ( 1.7% ) in both populations . in worldwide comparison differences in the frequency of mutations the polish population of fap patients belongs to the group where 39273931delaaaga occurred with higher frequency , whereas the frequency of mutation 31833187del - acaaa occurred with medium frequency in comparison with other populations . the two recurrent mutations localized on exon 11 were observed only in the polish population . in our two unrelated families with 14901491inst brain tumours were observed . another mutation ( q978x ) did not occur with higher frequency as described for other populations . in our fap patient group q283x , which occurs with frequency of 4.5% in uk fap patients , screening for these mutations permitted us to diagnose 19% of all families in our population but eight types of mutations constitute 43.5% of all our diagnosed families . the mutation study in our population should involve these eight mutations to improve molecular diagnostics of the apc gene . the study was financed by grant 2p05a10728 from the ministry of science and higher education .

the molecular diagnostics of genetically conditioned disorders is based on the identification of the mutations in the predisposing genes . hereditary cancer disorders of the gastrointestinal tracts are caused by mutations of the tumour suppressor genes or the dna repair genes . occurrence of recurrent mutation allows improvement of molecular diagnostics . the mutation spectrum in the genes causing hereditary forms of colorectal cancers in the polish population was previously described . in the present work an estimation of the frequency of the recurrent mutations of the apc gene was performed . eight types of mutations occurred in 19.4% of our fap families and these constitute 43% of all polish diagnosed families .

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methods are described in detail in the supplementary material online , below is a brief summary . we used publicly available chip - seq data produced from the livers of human , macaque , mouse , rat , and dog for four liver - enriched tfs : cebpa , foxa1 , hnf4a , onecut1 ( schmidt et al . reads were mapped to each reference genome with bowtie2 ( langmead and salzberg 2012 ) with default parameters . numbers of mapped reads and quality metrics are shown in supplementary table s2 , supplementary material online , for the liver - enriched tfs . tf peaks were called as reproducible in both replicates if they overlapped by 75% reciprocally ( supplementary table s3 , supplementary material online ) . ( 2010 ) and were screened by eye for whether they have liver expression in mouse , rat , and dog ( based upon previously published rna - seq data , see supplementary material online ) , as well as whether they have clear 1:1 orthologs based on ensembl annotations and/or based on sequence similarity . the set of 1,373 liver expressed genes that are one - to - one orthologs across the 5 mammals was constructed based on a cut - off of 5 read fragments per kilobase of exon per million reads within the livers of mouse , rat , and dog . the binding level for orthologs across species 2015 ) . before running these analyses , for each tf and species , read alignment files were downsampled to the number of reads mapped in the replicate with the fewest number of reads . this approach combines the number of binding events , their binding intensity , and their distance from the tss into a single measure . specifically , binding level ( ais ) , where i is an orthologous gene in species s , is given by ais = log ( jkgijksdijks + 0.1 ) where k is a peak within 100 kb of the tss of gene i , gijks is the intensity of peak k for tf j in species s and dijks is the distance ( in bp ) from the tss to the summit of peak k. the region size used is 100 kb and is discussed further elsewhere ( wong et al . a pseudocount of 0.1 is added to the denominator to ensure this value is never zero . the mean and variance in binding level was calculated for all tfs and species was determined for all liver expressed genes . because the signal - to - noise ratio differs greatly across chip - seq experiments , binding levels were converted into standard scores ( for each species and tf ) so that they could be better compared across species . the standard scores of binding levels for each tf were then summed to obtain a single measure of binding level per gene . maximum - likelihood ancestral binding levels were reconstructed under a bm model in r using the ace function of the ape package ( paradis et al . enrichment levels for the histone modification markers were calculated using the same steps as for binding level . all sequence analyses reported were performed on peak and flank coordinates sliced from the 38 eutherian epo alignment ( release 74 ; cunningham et al . 2015 ) . peak sequences were taken as 100 bp from peak summits , while flanking regions were taken as 2 kb from peak ends that did not intersect other peaks or exons . these alignments were realigned with mafft ( l - ins - i method ; v6.882b ; katoh and toh 2008 ) . shared peaks across species were called based upon overlapping summits ( taken as the peak center ) within 150 bp of each other within the alignment . ancestral sequences at each node in the primate phylogeny were reconstructed using the prequel program of phast ( v1.3 ; hubisz et al . lrts were performed with the phylop program of phast to test for accelerated evolution within the human supplementary tables s1s3 , figures s1s9 , and text are available at molecular biology and evolution online ( http://www.mbe.oxfordjournals.org/ ) .

characteristics of pseudogene degeneration at the coding level are well - known , such as a shift toward neutral rates of nonsynonymous substitutions and gain of frameshift mutations . in contrast , degeneration of pseudogene transcriptional regulation is not well understood . here , we test two predictions of regulatory degeneration along a pseudogenized lineage : 1 ) decreased transcription factor ( tf ) binding and 2 ) accelerated evolution in putative cis - regulatory regions.we find evidence for decreased tf binding levels nearby two primate pseudogenes compared with functional liver genes . however , the majority of tf - bound sequences nearby pseudogenes do not show evidence for lineage - specific accelerated rates of evolution . we conclude that decreases in tf binding level could be a marker for regulatory degeneration , while sequence degeneration in primate cis - regulatory modules may be obscured by background rates of tf binding site turnover .

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the attack on the world trade center had the potential to overwhelm new york 's health services . initial estimates spoke of 10,000 people in each of the two towers , all of them either killed or injured . local hospitals prepared for the worst , and in the first few hours there were hundreds of patients with crush injuries and burns . horror and sadness has now been replaced by anger , fear , and the determination to be better prepared next time . this determination not only exists in politics but also in health care , and as with all attempts to enforce change there needs to be a period of collecting opinions and data . in this issue of critical care , there is a series of nine articles offering varied perspectives of the events of 11 september 2001 . louis cook is an advanced life support coordinator with the fire department of new york . on page 301 , he describes how the fire department of new york took charge , set up command and control , and then had to evacuate , replace lost personnel , and resume control after the tower collapsed . " this was a monumental task " , writes cook , " given the psychological impact of the event " . the command and control center was also staffed by the new york police department and , on page 304 , the deputy chief surgeon , charles martinez , describes his experiences , including the part he played in helping police to ensure surrounding buildings were not " used by terrorists to launch a subsequent attack ... with the specific aim of harming the rescue effort " . the article , co - authored by dario gonzalez , medical director for clinical affairs of the fire department of new york , concludes that , while the incident was dramatic , the lessons to be learnt " are the same as those from previous disasters " . on page 307 , j david roccaforte of bellevue hospital , only 2.5 miles ( 4 km ) from the world trade center , tells us how they reacted from how they triaged " as well as could be expected " to how it was " difficult to anticipate needs " . donald b chalfin , an attending intensivist at maimonides medical center , new york , offers on page 310 his eye witness observations of the attack as he sat in the city 's traffic . " like so many other physicians ... " he writes , " i was paralyzed knowing that i was unable to give help ... " . on page 312 , david crippen draws on his experience of the 1988 earthquake in armenia to suggest that , while specialized search and rescue teams may be useful , " a more cost - effective approach [ would be ] to teach life supporting first aid to the general public " . but whoever intervenes , whether it be medical personnel or the general public , there is potential psychological sequela post - traumatic stress disorder . jeffrey hammond and jill brooks state , on page 315 , that treating post - traumatic stress disorder has " only a marginal effect " , and that early intervention , in the form of critical incident stress management , can " limit the establishment of maladaptive and disruptive cognitive or behavioral patterns " , both in health personnel and victims . ron simon and sheldon teperman of the jacobi medical center , new york , were part of the hospital 's disaster committee and offer some straight - talking criticism of the city 's reaction . " the lack of communication probably resulted in more problems than all other factors combined " , they say , going on to suggest that " time , effort , and resources were wasted ... because of lack of direction and information " ( page 318 ) . at the time of writing , on page 321 , vlad kvetan suggests that , while new york absorbed the blow of the world trade center attack well , " major stress was placed on ... biohazard resources " . he suggests that because the internet has disseminated sophisticated information about bioterrorism , comprehensive guidelines on managing all kinds of outbreaks , from anthrax to smallpox , are needed . finally , in the concluding article on page 323 , kenneth mattox questions to what extent we are prepared , or can be prepared , for the unexpected , and whether the bureaucrats behind health care have the ability to make those preparations . the frameworks for multifaceted care required during disasters can only be created , he points out , " by leaving egos and personal agendas at the front door and working for a common benefit " . we hope this 10-part series of articles in critical care facilitates the opinion and data collecting that is required before changes in disaster preparedness can be enforced . the series is dedicated to the first responders fire , police , and medical personnel who attended the world trade center disaster of 11 september 2001 . they did not hesitate to place themselves in harm 's way to rescue the innocent , and without their efforts many more would have perished . the authors acknowledge david crippen 's assistance in the creation of this 10-part review series . this article , and the series it is part of , is dedicated to the first responders fire , police and medical personnel who attended the world trade center disaster of 11 september 2001 . they did not hesitate to place themselves in harm 's way to rescue the innocent , and without their efforts many more would have perished .

the attack on the world trade center had the potential to overwhelm new york 's health services . sadly , however , the predicted thousands of treatable patients failed to materialize . horror and sadness has now been replaced by anger , fear , and the determination to be better prepared next time . this determination not only exists in politics but also in health care , and as with all attempts to enforce change there needs to be a period of collecting opinions and data . this article introduces nine reviews in critical care offering varied health care perspectives of the events of 11 september 2001 from people who were there and from experts in disaster management .

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primary amenorrhea is usually the result of a genetic or anatomic abnormality . in young women with primary amenorrhea , it is commonly caused by x - chromosome aberrations such as in turner syndrome , but individuals with a normal chromosome complement and ovarian dysgenesis also exist . a 35-year - old female patient presented to our medical outpatient department with complaints of palpitation and chest pain of 6 months duration . patient had paroxysmal episodes of palpitations that lasted few minutes , resolved spontaneously , and were not associated with exertion or other aggravating factors . patient had chest pain that was retro - sternal , intermittent not related to exertion and resolved spontaneously . menstrual history revealed that she never attained menarche . on examination she had dolicocephaly , arachnodactyly , high arched palate , she was tall statured [ height 165 cm ; figure 1 ] , her arm span ( 176 cm ) was more than her height , arachnodactyly [ figure 2 ] , reduced upper to lower body segment ratio ( 0.83 ) , and she had positive wrist and thumb sign . patient had underdeveloped rudimentary breasts ( tanner stage 2 ) , sparse pubic hair ( tanner stage 1 ) , and absent axillary hair . cardiovascular examination revealed mid - systolic click with a late systolic murmur , other systems were essentially normal . her blood glucose , renal function tests , liver function tests , and serum electrolytes were within normal limits . echocardiogram echo / doppler revealed prolapse of anterior mitral leaflet , mitral regurgitation and normal left ventricular systolic function . she had low levels of estrogen ( estradiol-10 pg / ml ; normal 15 - 200 pg / ml ) , serum testosterone ( 0.16 pg / ml , normal 0.6 - 6.8 pg / ml ) , and progesterone ( 0.56 ng / ml ) . she had elevated levels of gonodotropins , follicle - stimulating hormone ( fsh ) ( 101.3 serum prolactin ( 12 ng / ml , normal 0 - 20 ng / ml ) and thyroid function tests ( free t4 - 9.2 mcg / dl , normal 4.6 to 11.2 mcg / dl ; tsh-3.49mu / l , normal 0.4 - 5.0 marfanoid habitus : tall stature , height 165 cm ; arm span to height ratio of 1.067 ; upper segment to lower segment ratio of 0.83 arachnodactyly with high metacarpal index mci list of investigations that contributed in diagnoses of primary amenorrhea perrault and his colleagues in 1951 published the first report on two sisters with gonadal dysgenesis and with additional sensorineural deafness . hypothesized that there is a form of ovarian dysgenesis that is inherited as an autosomal recessive , female - limited disorder . neurologic data are available on 14 of 21 girls ; 7 of 14 had neurologic abnormalities . they concluded that high incidence of neurologic anomalies suggest that ataxia or mental retardation may not be just coincidental findings , but pleiotropic manifestations of perrault syndrome . reported on two sporadic and two familial new cases with sensorineural hearing impairment and ovarian dysgenesis , which are the cardinal signs of perrault syndrome in females . reported on two pairs of sisters with gonadal dysgenesis and deafness , cerebral , and ocular involvement who developed a progressive , severe sensory , and motor neuropathy . based on the clinical observations of known patients ; two forms of ps may be distinguished : one apparently non - progressive form and another with apparently progressive axonal - cerebellar degeneration . nishi et al . reviewed 21 patients from the literature , added ataxic gait , pes equinovarus , nystagmus , limited extraocular movements to the spectrum of neurologic defects in ps . absence of deafness in a patient with xx female gonadal dysgenesis ( xx - gd ) does not rule out perrault syndrome because the patients could develop deafness much later , at an older age . most patients had moderate to severe sensorineural deafness with mutism among patients with early onset of deafness . the findings of abnormal body proportions noted in our patients have been previously reported by jacob et al . in their observation of two siblings with perrault syndrome with marfanoid habitus . the pathogenetic basis for the ps is still unclear . studied a small family of mixed european ancestry includes two sisters with well - characterized perrault syndrome . whole - exome sequencing of genomic dna from one of these sisters revealed exactly one gene with two rare functional variants : hsd17b4 . further studies on other families are awaited to confirm the homogeneity of the genetic defect and the underlying molecular defect . these issues were discussed with our patient . during the follow up visits , we noticed depression and suicidal tendencies . after a comprehensive psychiatric evaluation , she was diagnosed with major depression and was put on anti - depressant medication . we did not advice any therapy for mitral valve prolapse as the prognosis in asymptomatic patients with nonsustained arrhythmias and structurally normal hearts is quite good . thus , the potential deleterious effects of drug therapy probably outweigh any risk from the arrhythmia in this setting . similarly , no antibiotic prophylaxis or anti - thrombotic prophylaxis was suggested as present guidelines recommends endocarditis prophylaxis for patients only at the highest risk . perrault syndrome is a rare cause of primary amenorrhea or ovarian dysgenesis , but should be considered in a female child with deafness / mutism . several reported cases have some form of neurologic deficit but our patient did not have any obvious neurological signs or symptoms , but she had marfanoid habitus , an association that was described only once in the literature . the marfanoid features could be considered as a part of extended phenotype of perrault syndrome .

gonadal ( ovarian ) dysgenesis with normal chromosomes ( 46 , xx ) , xx female gonadal dysgenesis ( xx - gd ) is a rare genetically heterogeneous disorder . in 1951 , perrault reported the association of gonadal dysgenesis and deafness , now referred to as perrault 's syndrome . perrault syndrome is a rare autosomal recessive condition affecting both females and males ; only females have gonadal dysgenesis associated with sensorineural deafness , which is present in both sexes . we present a case of sporadic perrault syndrome in a 35-year - old female with primary amenorrhea , sensorineural deafness , marfanoid features and normal karyotype . there are very few case reports describing the condition , even lesser reports of association with marfanoid habitus . we report this case for its rarity and add to the spectrum of the disease that remains undetermined .

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posttraumatic avascular necrosis ( avn ) of the scaphoid is a common complication probably due to the precarious blood supply . the rate of incidence is about 13% to 40% and almost all are seen in the proximal fragment [ 2 , 3 ] . careful review of the literature revealed six cases of distal avn in three studies [ 4 , 5 , 6 ] . the diagnosis of avn of the scaphoid is made by combining the mri findings with direct observation of the punctuate bleeding during the operation . however , the diagnosis of avn is suspicious in these cases , as mri investigation had been performed in one case and preoperative bleeding was observed in the other . here , we report four new cases , all with the correlation of mri and punctuate bleeding . the series consisted of four patients aged 29 , 33 , 53 and 57 years . all had a history of scaphoid fracture following a fall on an outstretched hand 35 years ago , and all had been treated by casting before . radiographic examination revealed suspected areas , such as sclerosis and/or cystic changes , on the distal pole of the scaphoid ( figure 1 ) and mri views were identical with avn of the distal pole , showing hyperintense changes ( figure 2 ) . tourniquet was deflated in order to observe punctuate bleeding ; it was observed in three cases and the patients were treated by bone grafting and wire fixation ( figure 3 ) in the remaining , there was no punctuate bleeding despite drilling and the scaphoid was excised and radial advancement osteotomy ( figure 4 ) was performed . treated by bone grafting and wire fixation . scaphoid was excised and radial advancement osteotomy . all patients were evaluated by quick disabilities of shoulder , arm , and hand score 711 years after the operation by telephone interview . according to this score , 11 questions related to daily living posttraumatic avn of the scaphoid occurs as a result of impairment of the vascular supply to the involved bone fragment . several studies had demonstrated a strikingly poor blood supply to the proximal pole , particularly in comparison with the abundant supply to the distal two - thirds of the scaphoid [ 1 , 2 ] . review of the literature revealed six cases in three reports [ 4 , 5 , 6 ] . , avn in the distal fragment occurs if the volar vessel is damaged and the fracture line is distal to the line of entry of the dorsal vessels . another explanation maybe the anomalous different vascularization of the distal pole [ 5 , 6 , 9 ] . the diagnosis of avn of the scaphoid was made by combining the mri findings with direct observation of the punctuate bleeding during the operation . however , there is no such approach in the previously described cases [ 4 , 5 , 6 ] . in the case of sherman et al . , mri was not available and there was no chance to observe bleeding , as the patients had refused surgical treatment . similarly , in the case of the garg et al . , although mri suggested avn , the patient had been treated conservatively , so there was no chance for punctuate bleeding , and the fracture united . the diagnosis is also suspicious in this case as no correlation was possible and the fracture had healed . according to herbert , avn means irreversible necrosis or death of bone and healing is impossible . only one case had been operated . in this case , the authors had confirmed avn by the pinning attempt that had failed . there seems no such method for the diagnosis of avn , so the diagnosis is again in doubt . in our opinion , all these cases should be labeled as suspected avn . in three of our cases , although preoperative mri suggested avn ( figure 2 ) , punctuate bleeding was observed during the operation and all were treated by pinning and grafting and healed uneventfully . in those cases , the appearance of avn was probably due to the normal marrow of bone that has not been established yet , but bleeding was observed due to revascularition . in the remaining case , mri suggested avn along with lack of punctuate bleeding and scaphoid was excised and radial advancement osteotomy was performed . in conclusion , all six cases reported before [ 4 , 5 , 6 ] , and three of our cases that were treated by pinning and had healed , were not real avn or the diagnosis was doubtful . so our fourth case seems to be a unique case of distal pole avn of the scaphoid in the literature .

abstractavascular necrosis ( avn ) of the scaphoid predominantly occurs in the proximal pole . review of the literature revealed only six cases and all are suspect due to the lack of either mri investigation or investigation of bleeding preoperatively . we report four new cases and one of them appears to be a real distal pole avn of the scaphoid in the literature .

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steven johnson syndrome ( sjs ) is characterized by sudden onset of erosion of mucous membranes ( predominantly oral mucosa , lips , and conjunctivae ) with widespread blistering of the skin involving up to 10% of the body surface area . trimethoprim - sulfamethoxazole ( tmp / smx ) is a widely prescribed antimicrobial for the management of several uncomplicated infections . in immunocompetent persons , the adverse reactions to tmp / smx occur in approximately 1 - 3% of persons . in contrast , in hiv - infected population , a much higher incidence of adverse reactions has been reported with frequencies ranging from 40 - 80% . we report a hiv - infected man who developed sjs while receiving tmp / smx therapy . a 33-year - old male presented with complaints of intermittent low grade fever for two months , cough with expectoration for one and half month , loss of weight , and appetite for one month . the patient was afebrile with a pulse rate of 92/min , respiratory rate of 30/min and blood pressure of 120/70 mmhg . investigations revealed : hemoglobin 9.2 gm / dl , total leucocyte count 7500/cumm with an absolute lymphocyte count of 1500/cumm , platelet count of 2.1 lac / cumm and erythrocyte sedimentation rate of 76 mm at the end of 1 hr . hiv - elisa was positive . in view of the clinical presentation and investigations , a diagnosis of pneumocystis jirovecii pneumonia ( pcp ) was considered and the patient was started on tmp / smx doubles strength two tablets thrice daily . after ten days of starting tmx / smx therapy , the patient developed high grade fever , redness and pricking sensation in eyes , and burning sensation in throat . within the next 48 hours he developed blepharitis , conjunctival congestion , erythema of the eyelids , and oral mucosal erosions [ figure 1 ] . painful , erythematous , maculopapular , and vesicular lesions appeared all over the body including genitals [ figure 2 ] . there were multiple ulcerations in the buccal mucosa , floor of the mouth , and ventral surface of the tongue . the patient was hemodynamically stable with a pulse rate of 102 per / min and a blood pressure of 110/80 mmhg . the alanine aminotransferase and aspartate aminotransferase levels were 250u / l ( 10 - 40u / l ) and 155u / l ( 10 - 35u / l ) , respectively . the patient was treated aggressively with intravenous dexamethasone 6 hourly , intravenous fluids , prophylactic antibiotics , anti - allergic drugs and local treatment of lesions . re - epithelialization of the previously sloughed areas occurred and the general condition of the patient remained satisfactory . he was discharged after a month by which time the skin had healed with post - inflammatory hypopigmentation . desensitization to tmp / smx was not attempted and the patient was discharged on dapsone prophylaxis for pcp . clinical photograph showing conjunctival congestion , erythema of the eyelids , and blepharitis clinical photograph showing cutaneous lesions all over the body with oral mucosal erosions tmp / smx is commonly used for the treatment and prophylaxis of pneumocystis jirovecii pneumonia ( pcp ) in hiv - infected patients . in addition to its efficacy in preventing pcp , tmp / however , the administration of tmp / smx is hampered by the high incidence of hypersensitivity reactions in these patients . the most common adverse reactions include nausea , vomiting , anorexia , dermatological reactions such as pruritis , urticaria and less commonly steven johnson syndrome ( sjs ) , neutropenia , exfoliative dermatitis , erythema multiforme and toxic epidermal necrolysis . a pubmed search using the keywords trimethoprim - sulfamethoxazole and steven johnson syndrome and human immunodeficiency virus revealed less than ten cases being reported in literature till date . the increased incidence of adverse reactions to tmp / smx in hiv - infected patients is due to the hydroxylamine derivative of sulphamethaxazole , i.e. , sulphamethaxazole hydroxylamine . the deficiency of glutathione enzyme in hiv - infected patients results in a decreased capacity to scavenge these hydroxylamine derivatives . in vitro , it has been found that as compared to cd8 cells , purified cd4 cells are more resistant to the sulphamethaxazole hydroxylamine . in hiv infection , the depletion of cd4 cells leaves a greater proportion of circulating t - cells as the more susceptible cd8 subset . in addition , the immune dysfunction observed in hiv - infected patients , i.e. , the polyclonal b - cell activation , polyclonal gammopathy , and decreased t - suppressor cell functions leads to an exaggerated humoral immune response to smx or its metabolites . other factors such as viral load and concurrent medications may also increase cell sensitivity to reactive metabolites . it is not clear whether the adverse reactions to tmp / smx merely indicate or also induce progression of hiv disease . veenstra et al . found that patients with adverse reactions to tmp / smx have a more rapid decline in cd4 cell counts and rapid progression to aids and death . in patients with non life - threatening adverse reactions ( e.g. , fever , rash ) , rapid or slow oral desensitization to tmp / smx can be attempted . however , in patients with severe life threatening adverse reaction to tmp / smx , alternative drug like dapsone , pentamidine , or atovaquone should be given for pcp prophylaxis . those who do not tolerate or have recurrent pcp infections despite alternative therapy could be subjected to a trial of desensitization to tmp - smx under close supervision . this case illustrates a clinically important and life threatening adverse effect of tmp / smx in hiv - infected patients . due to the high incidence of such hypersensitivity reactions

trimethoprim - sulfamethoxazole ( tmp / smx ) is a widely prescribed antimicrobial for the management of several uncomplicated infections . it is commonly used for the treatment and prophylaxis of pneumocystis jirovecii pneumonia ( pcp ) in the hiv - infected population . the adverse reaction to tmp / smx is more frequent and severe in hiv - infected patients as compared to the general population . here , we report a case of stevens - johnson syndrome ( sjs ) secondary to tmp / smx . the patient had a generalized cutaneous reaction with involvement of the eyes , oral cavity , and genitals . he had elevated hepatic alanine aminotransferase and aspartate aminotransferase enzyme . tmp / smx therapy was stopped and supportive treatment was started . his condition improved after eight days of stopping tmp / smx therapy .

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a study on serologic and molecular characterization of denv isolates was initiated in january 2005 at the fundao de medicina tropical do amazonas ( fmtam ) . parasite - negative patients who had clinical symptoms of malaria were invited to participate in the study . each patient received essential information and signed a consent form approved by the fmtam ethical committee . all serum samples were collected during the acute phase of illness and tested for denv infection by using 3 methods . the first method was virus culture , for which serum samples were placed on the aedes albopictus cell line c6/36 grown in leibovitz-15 medium containing 5% fetal bovine serum , followed by viral antigen identification with type - specific monoclonal antibodies in an indirect immunofluorescence assay ( 8) . the second method was detection of immunoglobulin m antibodies to denv by an elisa on serum samples from patients > 7 days after onset of symptoms ( 9 ) . pcr ( rt - pcr ) protocol on the basis of that described by lanciotti et al . briefly , viral rna was extracted by using the qiaamp viral rna mini kit ( qiagen , valencia , ca , usa ) , and reverse transcription was conducted on 5 l of extracted rna with superscript iii ( invitrogen , carlsbad , ca , usa ) and random primers . after incubation for 1 h at 50c , 2 l of each cdna was subjected to pcr amplification with d1 and d2 primers for 35 cycles consisting of 1 min at 94c , 1 min at 55c , and 1 min at 72c , and a final extension for 10 min at 72c . a second round of amplification was conducted with 10 l ( diluted 1:100 ) of the first amplicon , a mixture of type - specific reverse primers ( ts1ts4 ) , and the conserved forward primer d1 . denv-4 was detected in 3 samples ( am750 , am1041 , and am1619 ) by virus culture or rt - pcr . it was identified as a co - infecting virus with denv-3 in isolate am750 ; samples am1041 and am1619 represented single denv-4 infections ( table ) . to confirm these results , generated amplicons were cloned into a ta vector ( invitrogen ) , and > 3 colonies for each sample were sequenced in both directions by using the bigdye terminator cycle sequence kit ( applied biosystems , foster city , ca , usa ) . denv-3 and denv-4 nucleotide sequences obtained were subjected to a basic local alignment search tool ( blast ) ( www.ncbi.nlm.nih.gov/ ) analysis that used the megablast algorithm optimized for highly similar sequences . using this approach , we obtained sequences with identities ranging from 95% to 99% for denv-3 and 94% to 98% for denv-4 for isolates am750-d3 , am750-d4 , and am1619 . eu127898 ( am750-d3 ) , eu127899 ( am750-d4 ) , and eu127900 ( am1619 ) . * igm , immunoglobulin m ; m - pcr , multiplex typing pcr described by lanciotti et al . ( 10 ) ; s - pcr , single serotype - specific primer pcr ; d , dengue serotype ; blast , basic local alignment search tool ; ns , not sequenced . isolate am750 is from a person with a co - infection ; different clones were sequenced . the 3 denv-4positive samples were obtained from patients who lived and worked in manaus and reported no travel history for > 15 days before onset of symptoms . these samples were obtained during another study that identified 62 denv - positive samples from january 2005 through june 2007 ( 24 denv-2 , 35 denv-3 , and the 3 denv-4 cases in our study ) among 128 samples tested from patients in 14 municipalities in amazonas . since its introduction into the western hemisphere in 1981 , denv-4 has been associated with dengue fever and only sporadically associated with serious cases of dhf or dss ( 1 ) . a study in colombia found more dhf patients infected with denv-2 than with denv-3 or denv-4 ( 11 ) . conversely , another study showed an association of denv-4 with an epidemic of dhf that occurred in mexico in 1984 ( 12 ) . there are many host ( and perhaps viral ) factors in dengue infections that may lead to development of dhf . on the basis of the antibody - dependent enhancement hypothesis , the most important factors would be those generated by the patient s immune response upon secondary infections ( 13 ) . the 3 isolates reported in our study were from patients with no travel history , which indicates that denv-4 is present in manaus . detection of denv-4 in brazil co - circulating with other denv serotypes endemic to this country represents an increased risk for dhf or dss because many persons have been sensitized by previous dengue infections but are not protected against infection with denv-4 . the first report of denv-4 in brazil was in the state of roraima in 1982 . since that time , no other isolate of denv-4 has been reported in any part of brazil ( 14,15 ) . the resurgence of denv-4 in the amazon region of brazil most likely resulted from the proximity of brazil to denv-4endemic countries ( venezuela and colombia ) . additional genotyping studies are being conducted to verify this assumption and to obtain information on dengue epidemiology in brazil . our study documents the detection of denv-4 in manaus , amazonas , and the first isolation of this serotype in brazil in 25 years . these findings reinforce the need for continual epidemiologic studies and use of classic and molecular approaches in the surveillance of emerging or reemerging diseases .

we report dengue virus type 4 ( denv-4 ) in amazonas , brazil . this virus was isolated from serum samples of 3 patients treated at a tropical medicine reference center in manaus . all 3 cases were confirmed by serologic and molecular tests ; 1 patient was co - infected with denv-3 and denv-4 .

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a total of 226 bengali medium students ( male 99 and female 127 ) , studying in class seven and eight , were taken from two urban and two rural schools of west bengal . jepqr - s developed by corulla is 48 item self - reported questionnaire having four dimensions extraversion , neuroticism , psychoticism , and lie scale each of which has 12 items . the items of the questionnaire were translated into bengali by two bilingual bengali personnel . where there were inconsistencies , both translation of the questionnaire by an expert was made and where there were any inconsistencies , the translators were consulted to get best possible solutions . internal consistency of each items of each of the four subscales of the translated jepqr - s was completed . inter - correlations between different subscales were also found . to find internal consistency of items under a subscale , item rest of test correlations were found . the internal consistency of the subscales of the translated questionnaire was found by calculating chronbach 's alpha . the statistical analysis was made with the help of statistical package for the social science ( spss ) statistics 17.0 . a total of 226 bengali medium students ( male 99 and female 127 ) , studying in class seven and eight , were taken from two urban and two rural schools of west bengal . jepqr - s developed by corulla is 48 item self - reported questionnaire having four dimensions extraversion , neuroticism , psychoticism , and lie scale each of which has 12 items . jepqr - s developed by corulla is 48 item self - reported questionnaire having four dimensions extraversion , neuroticism , psychoticism , and lie scale each of which has 12 items . the items of the questionnaire were translated into bengali by two bilingual bengali personnel . where there were inconsistencies , both the translators were consulted . also back translation of the questionnaire by an expert was made and where there were any inconsistencies , the translators were consulted to get best possible solutions . internal consistency of each items of each of the four subscales of the translated jepqr - s was completed . to find internal consistency of items under a subscale , item rest of test correlations were found . the internal consistency of the subscales of the translated questionnaire was found by calculating chronbach 's alpha . the statistical analysis was made with the help of statistical package for the social science ( spss ) statistics 17.0 . table 1 presents that the item rest of test correlations vary for the extraversion between 0.082 and 0.417 , for neuroticism between 0.127 and 0.552 , for psychoticism between 0.085 and 0.504 , and for the lie scale between 0.051 and 0.363 . item rest of test correlations alpha reliability found for the four subscales were 0.620 for extraversion , 0.663 for neuroticism , 0.604 for psychoticism , and 0.620 for lie scale . the test retest reliabilities were found 0.659 for extraversion , 0.652 for neuroticism , 0.631 for psychoticism , and 0.621 for lie scale . the present study was aimed to examine to what extent the bengali translation of the jepqr - s is functional in bengali cultured population . the results [ table 1 ] of the first stage of data analysis indicate that most of the items within a subscale have significant correlations with rest of the items . the alpha coefficients of all the four subscales recorded in this study do not cross 0.7 , the level recommended by kline , but they are very close to it and satisfactory . alpha coefficients for extraversion , neuroticism and lie scale recorded in this study are less well relative to main stream studies , perhaps , due to cultural difference , as a measuring tool like personality test is always culturally loaded . significant observation of this study is that the alpha coefficient of 0.604 for psychoticism is impressive against the historic difficulties encountered by the subscale . retest reliabilities found in this study are satisfactory and the results are very similar to the findings of eysenck and eysenck which were for 13 years boys and girls with an interval of 6 months ; extraversion 0.67 and 0.76 , neuroticism 0.72 and 0.74 , psychoticism 0.63 and 0.66 , and lie scale 0.65 and 0.66 . results relating to the main stream questionnaires provide that the dimensions of personality are not all orthogonal . the inter correlations [ table 2 ] between the dimensions of the translated jepqr - s of the present study also show that they are not all orthogonal . neuroticism and lie scale also showed negative correlation significant at the 0.05 level . on the other hand , extraversion and lie scale also neuroticism and psychoticism both showed positive correlations significant at the 0.05 level . however , there is a significant negative correlation at the 0.01 level between psychoticism and lie scale while extraversion is independent of neuroticism . on the basis of the present study , it may be concluded that the bengali version of the jepqr - s may be accepted as a functional tool for research work and educational purpose . it is further recommended to administer the bengali version of jepqr - s on a larger sample for determining the psychometric properties more accurately .

background : personality measuring instrument plays an important role in many fields of human civilization and therefore , present study was aimed to find such an instrument for bengali speaking juniors.materials and methods : bengali translation of the short - form of the revised junior eysenck personality questionnaire developed by corulla was administered on a sample of 226 bengali speaking students ( 99 boys and 127 girls ) studying in class seven and eight taken from two urban and two rural schools . internal consistency of each item under a subscale was calculated ; internal consistency of each of the four subscales of the translated questionnaire was calculated ; test retest reliability was found with an interval of 3 months and inter - correlations between different subscales were found.conclusion:the findings provided satisfactory psychometric properties of the extraversion , neuroticism , psychoticism , and lie scale .

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bone scintigraphy is an important modality for the examination of various pathological conditions of the skeletal system . radionuclide bone imaging is quick , relatively inexpensive , widely available , and exquisitely sensitive and is invaluable in the diagnostic evaluation of numerous pathological conditions . these compounds accumulate rapidly in bone , and by 2 - 6 h after injection , about 50% of the injected dose is in the skeletal system . tc - methylene diphosphonate ( tc - mdp ) imaging , customarily directed toward identifying altered skeletal metabolism , has been used extensively to image a variety of extraosseous lesions , especially heterotopic ossification and metabolic , metastatic calcification . we report a rare case of accumulation of bone scintigraphy tracer in a phlebolith in a patient of adenocarcinoma of lung . a 43-year - old female patient , known case of adenocarcinoma of right lung was referred for a tc - mdp bone scan with complaint of persistent low backache since 3 months . the scan showed abnormal , focal increased tracer uptake in left pelvic cavity , not localizing to any bone of the skeleton [ figures 1a and b , arrows ] . the uptake was persistent even in post - void imaging done after adequate hydration , giving us a clue that it was not due to tracer hold up in the ureter . on single photon emission computed tomography and computed tomography ( spect - ct ) imaging , the focal tracer uptake localized to a small focus of calcification in the left pelvic cavity away from the ureter [ figure 2 , arrow ] . an additional ultrasonography of the pelvis confirmed that there was no ureteric calculus [ figure 3 ] . review of the patient 's recent contrast - enhanced computed tomography revealed a phlebolith in left iliac vein ( ct hounsfield unit : 338 ) . thus , we concluded the extraosseous tc - mdp uptake was due to phlebolith in the left iliac vein . planar bone scan ( a and b ) of a 43-year - old female patient , a known case of adenocarcinoma of right lung . focal , intense tracer uptake seen in left pelvic cavity ( arrow ) correlative single photon emission computed tomography and computed tomography fusion imaging localized this uptake to a phlebolith in left iliac vein ( arrow ) ultrasonography of the pelvis showing ureteric jets bilaterally ( arrows ) , ruling out obstruction ( calculus ) in the ureter tc - mdp , a bone scan tracer , has rapid blood clearance , excellent in vivo chemical stability , and a high bone - to - soft tissue ratio , which are ideal for bone imaging . although tc - mdp is customarily used to evaluate skeletal pathological conditions , its excellent clearance from normal soft tissues allows the detection of abnormal extraskeletal tc - mdp accumulation . it is hypothesized that tc - mdp and its analogues bind to bone by adsorption to the surface of the hydroxyapatite crystal . while in soft tissue , these pathways result in uptake of tc - mdp through what is believed to be chemisorption of the radiopharmaceutical onto the surface of the calcium salts . phleboliths are deposits which develop in the wall of a vein and are composed of calcium or lime . these are most commonly seen in the lower pelvis and sometime occur in large numbers . they are often confused with ureteric stones when seen around the urinary bladder in the pelvic cavity . however , on plain radiographs , these can be distinguished from a calculus due to the presence of a translucent center and circular or oval shape.[810 ] bone scan tracer uptake in a phlebolith has been described in past . dystrophic calcification occurs in patients with normal ca + and po4 levels and refers to ca + deposition in tissues secondary to histological disruption caused by trauma , ischemia , or cellular necrosis or in the enzymatic necrosis of fat . it is thought that calcium ion binds to phospholipids present in membrane bound vesicles , phosphatases generate phosphate groups which in turn bind to the calcium , and the cycle is repeated until local concentrations are elevated and crystals begin to form . hyaline collagen degeneration , a consequence of tissue damage , is particularly associated with ca + deposition . similar mechanism operates in other known causes of extraskeletal bone scan tracer uptake in tissue infarction , deep vein thrombosis , scars , and dermatomyositis . to conclude , we report a rare case of extraosseous uptake of bone scan tracer in a phlebolith . with growing use of integration of ct with spect , nuclear medicine physicians should become aware of such anatomical changes and variants so as to avoid misinterpretation . the awareness of the underlying pathophysiological basis of these changes and uptake of mdp in extraosseous soft tissue can significantly enhance the interpretation and diagnostic value of bone scintigraphy .

uptake in non - osseous , non - urologic tissues is occasionally found in the performance of bone scintigraphy . these uptakes reflect an atypical interaction between the radiopharmaceutical and the patient . knowledge of the rare extraskeletal uptakes and their clinical relevance helps in better interpretation of bone scans . we report an unusual occurrence of extraosseous accumulation of 99mtc - methylene diphosphonate in a phlebolith in bone scan , confirmed with the aid of photon emission computed tomography and computed tomography .

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in a recent issue of critical care , morgan and colleagues present the results of a well - conducted systematic review and meta - analysis of the effect of statin therapy on inflammatory markers after cardiac surgery . observational evidence suggests that statin therapy may dampen the inflammatory response following exposure to a significant trigger and there is currently much interest in using statins to treat sepsis . in this context cardiopulmonary bypass ( cpb ) is appealing methodologically because it allows the study of preventive interventions [ 4 - 6 ] . fortunately for patients , mortality following cpb is low , but the methodological downside of this success is that very large trials of low risk patients ( or somewhat smaller trials of higher risk patients ) are needed to show a mortality effect . the randomised controlled trials included by morgan and colleagues measured post - operative inflammatory markers in adults receiving a statin or placebo prior to cpb . they found that statin therapy may reduce post - cpb inflammation as measured by il-6 , il-8 , c - reactive protein and tumour necrosis factor - alpha . for example , six of the eight apparently randomised studies provide no information on sequence generation and allocation concealment . three were unblinded and only two had a low risk of bias ( defined by applying the cochrane risk of bias tool ) . the median sample size was 43.5 ( range 20 to 200 ) and the confidence intervals around the mean differences in inflammatory markers for individual studies and for the summary estimates were fairly wide . other studies of inflammatory biomarkers are likely to vary widely between patients and within patients over time , suggesting that analysis of within - patient changes over time may detect differences between treatment groups with more statistical power . while the meta - analysis does not provide a definitive answer , it raises key methodological issues relevant to sepsis research in general , and to statin research in critical illness in particular . the methodological quality of many of these studies is variable and frequently the mechanisms ( at both biological and functional levels ) through which benefit are supposed to accrue were not robustly described . we agree with other authors that the logical sequence of questions to answer before performing pragmatic mortality trials should be : first , can statins theoretically beneficially modulate the immune response in these patient populations ? second , do statins beneficially ( and safely ) modulate the immune response and associated physiology ? third , does the modulated immune response translate into benefit at the level of organ function ? in this regard the critical care research community can learn much from colleagues in rheumatology , cardiology and oncology , who have explored and described mechanistic pathways - paths reliably connecting biological plausibility and effect with organ performance and then outcomes important to patients ( for example , mortality ) ; and developed reliable and validated surrogate endpoints . morgan and colleagues want to establish whether potential surrogate endpoints ( inflammatory markers ) are modulated , but herein lay the problems . second , while data from successful ' mortality ' randomised controlled trials may improve our understanding of surrogate outcomes , interventions that improve surrogate markers do not necessarily translate into improved mortality [ 12 - 14 ] . third , what is the minimum clinically important difference for a biomarker or combination of biomarkers ? how much should individual ( and aggregate ) marker levels differ between groups to translate into clinical benefit ? lastly , what if ' good ' markers are also suppressed and , indeed , how much inflammation is good for you ? it is clear that in this relatively new study area the knowledge space is already occupied by poor studies and potentially unreliable data . we would like to encourage investigators to design studies that are methodologically robust and provide reliable mechanistic data . icu researchers should work towards developing valid surrogate endpoints to allow robust and reliable translational research , although we acknowledge that previous success at improving organ performance has not always improved outcomes [ 12 - 14 ] . once validated , these surrogate endpoints should be used to establish the biological effectiveness of new treatments ( and probably some existing ones ) before moving on to pragmatic studies using mortality as outcome measure . without demonstrating first biological and then functional ( for example , organ performance ) effectiveness , we run the risk of wrongly adding statins to the wasteland of icu pharmacotherapy . on the positive side , the pleiotropic effects of statins and extensive experience with these agents in cardiology mean that we may be less likely to fall into a trap constructed of an insufficient understating of mechanisms combined with a single - target therapy .

statin therapy may prevent an excessive inflammatory response after cardiopulmonary bypass for cardiac surgery . in a recent issue of critical care , morgan and colleagues present data from a well - conducted systematic review and meta - analysis of randomised controlled trials using inflammatory markers as primary outcome measure . they find that pre - operative statin therapy , compared with placebo , may reduce various post - operative markers of systemic inflammation ( il-6 , il-8 , c - reactive protein , tumour necrosis factor - alpha ) . their ability to make definitive conclusions is limited , however , by the suboptimal methodological quality of the primary studies . their review suggests that icu researchers should focus on developing valid surrogate markers and use these to accurately describe the mechanisms and effectiveness of novel therapies before proceeding to large pragmatic trials using mortality as primary outcome .

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rituximab is a relatively novel medication for immunomodulation in current clinical practice . with its use becoming fairly widespread and newer indications being approved at a fast rate it is also imperative to watch for any adverse reactions , which may need monitoring parameters during therapy a 54-year - old man was diagnosed with limited form of wegener 's granulomatosis 1 year before the current hospitalization . he had failed therapy with corticosteroids and was recommended rituximab for resistant disease state . besides lung and upper airway involvement , he had no other organ involvement from wegener 's disease . five days after receiving the infusion he developed postural dizziness and had near syncopal episodes , which led to hospital admission . he denied chest pain , shortness of breath , fever , palpitations , and any rash . vital signs on admission revealed hypotension with a blood pressure of 80/40 mmhg , pulse 75 beats / min , respiratory rate 20/min , and temperature 98f . electrocardiogram ( ecg ) showed a new onset left bundle branch block ( lbbb ) [ figure 1c ] as compared to his prior ecg performed a month back before the current admission [ figure 1a ] . in view of new lbbb , an urgent transthoracic echocardiogram was performed revealing normal left ventricular systolic function and absence of wall motion abnormalities . patient was admitted to intensive care unit and was treated with intravenous fluids and inotropic agents for hypotension . contrast - enhanced cardiac magnetic resonance imaging was conducted to rule out focal myocarditis as a cause of the new onset lbbb ; and failed to show any abnormality . on day 2 of admission , telemetry showed intermittent lbbb [ figure 1b ] and eventually the lbbb was replaced by a narrow qrs complex [ figure 1d ] with only supportive treatment . patient remained hemodynamically stable off inotropic agents and was discharged home and is doing well on follow up . telemetric strip new onset left bundle branch block ( lbbb ) intermittent sinus beats with lbbb and finally resolution of lbbb rituximab , the first monoclonal antibody approved by the united states food and drug administration ( fda ) for the treatment of malignant disease , is being used to treat a wide variety of conditions in modern practice , including non - hodgkin 's lymphoma , wegener 's granulomatosis , rheumatoid arthritis , thrombotic thrombocytopenic purpura , among many others . currently , four adverse effects that warrant a " black box " warning in the package insert are known : infusion reactions , tumor lysis syndrome , mucocutaneous reactions , and progressive multifocal leukoencephalopathy . it is also known to promote severe orthostatic hypotension often associated with allergic symptoms , urticaria , bronchospasm , and angioedema . most adverse events occur during or after the first infusion of rituximab , and the number and severity of adverse events decreases with subsequent infusions . as with any novel therapy , new adverse reactions are being noted with increasing time and usage . in a multicenter phase ii study conducted to assess the toxicity and response rates to rituximab in b - cell malignancies that express cd20 , 10 out of 131 patients developed an arrhythmia with treatment . these included bradycardia ( n = 3 ) , atrial fibrillation ( n = 2 ) , and nonspecified arrhythmia or tachyarrhythmia ( n = 5 ) . one other patient had palpitations , and another was noted to have premature ventricular complexes . in most cases , ventricular tachycardia during the infusion of rituximab and prompt disappearance after discontinuation of infusion was first reported in 2005 . complete atrioventricular block induced by rituximab monotherapy in an 83-year - old has also been described in literature . another recent report of polymorphic ventricular tachycardia causing syncope during initial infusion of rituximab raises concerns of arrhythmogenic side effects of this medication . despite these reports a study to determine the maximum tolerated infusion rate of rituximab with special emphasis on monitoring the effect of rituximab on cardiac function concluded with confirmation of lack of cardiotoxic effect of a fast infusion rate . however , we could not come across any reported case of lbbb associated with rituximab infusion . increased ventricular dysfunction after rituximab infusion has been seen which is attributed to growth of reticulin fiber in cardiac myocytes . reticulin deposition may have an effect on conduction system causing rhythm abnormalities and interventricular conduction delays as seen in our patient . it is also hypothesized that the drug affects conduction by inhibiting the calcium - ion channel properties of the cd20 antigen , which could lead to formation of early after depolarizations . still the mechanism by which rituximab may cause arrhythmias is presently unclear and needs more research . also , it would be prudent to keep patients on electrocardiac monitoring during drug infusions to monitor for possible conduction abnormalities , especially the initial infusions .

rituximab ( a monoclonal antibody directed against cd 20 ) therapy can be acutely complicated by infusion reactions and cardiac arrhythmia on rare occasions . we report the first case of a new onset left bundle branch block ( lbbb ) after rituximab therapy for wegener 's vasculitis .

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gallstone ileus causing small bowel obstruction is a well - document phenomenon ; however , gallstones causing large bowel obstruction are much rarer and almost always secondary to existing bowel pathology . we report what we believe to be the first case of large bowel obstruction caused by an impacted gallstone without primary pathology distal to the stone and discuss potential management options from the literature to rationalize our choice of a defunctioning loop colostomy with the stone left in situ . a 92-year male , with no significant co - morbidities apart from peptic ulcers , was admitted with 6 days of obstination . on examination blood showed features of dehydration and plain abdominal x - ray demonstrated both small and large bowel dilatation , but no obvious causal pathology . a contrast - enhanced computed tomography scan revealed a 2.5-cm partially calcified gallstone impacted at the descending colon - sigmoid junction ( fig . 1 ) . 2 ) , with a further smaller gallstone in the caecum ( fig . 3 ) . the offending gallstone could be seen incidentally in the gallbladder on imaging 3 years previously ( fig . figure 1:large gallstone impacted in the descending colon - sigmoid junction , causing large bowel obstruction proximally . figure 2:cholecysto - colic fistula , with a thick - walled , dilated , gallbladder . figure 3:ct reconstruction showing the impacted gallstone and a smaller incidental gallstone in the caecum . large gallstone impacted in the descending colon - sigmoid junction , causing large bowel obstruction proximally . the patient was initially resuscitated , although he could not tolerate an naso - gastric tube . this failed due to a large amount of faecal matter distal to the stone , despite several phosphate enemas . in light of worsening abdominal distension and pain , the patient underwent a lower midline laparotomy where the hugely dilated small bowel was decompressed via the stomach , the descending colon mobilized and the diagnosis confirmed . there was indeed no primary pathology distal to stone ; however , the stone could not be disimpacted , and the overlying colonic wall was viable with no evidence of ischaemia . considering the patient 's age and physiological reserve , the duration of large bowel obstruction , high morbidity and mortality associated with emergency surgery , and the fear of leak following a colotomy , an on - table decision was made to perform a proximal defunctioning loop transverse colostomy to relieve the obstruction . the cholecysto - colic fistula was left untouched , and the impacted stone left in situ . he will be brought back to the clinic to discuss the options with regard to removal of stone and reversal of his colostomy . gallstone ileus is not an uncommon phenomenon ; however , large bowel obstruction due to stone impaction is rarely seen due to the large calibre of the colon , with few case reports in the literature [ 2 , 3 ] . the site of impaction is usually the sigmoid [ 3 , 4 ] , with retention of the stone as a result of a stricture from diverticular disease or previous radiotherapy . the stone is thought to enter the colon via a cholecysto - colic fistula , developing during a bout of acute cholecystitis affecting the hepatic flexure . cases usually present with features of large bowel obstruction ; however , colonic gallstones may also present atypically with non - specific symptoms such as diarrhoea , cholangitis or bleeding from the fistula tract . the diagnosis is best made on computed tomography ( ct ) . a trial of conservative treatment may be attempted , and colonoscopy with and without lithotripsy has been successful in relieving obstruction ; however , surgery may be needed if the stone can not be retrieved and will not pass spontaneously . there is no definite consensus as to how a gallstone impacted in the colon should be treated . the options are a combination procedure of enterolithotomy , cholecystectomy and fistulectomy , or enterolithotomy alone with or without a covering loop colostomy to resolve the immediate obstruction [ 2 , 3 ] . the former leads to relief of the obstruction as well as preventing further stone formation and episodes of cholangitis ; however , as these patients are invariably elderly and bearing significant co - morbidities , a minimalistic approach is often preferable . in our case a laparotomy was undertaken as endoscopy failed and the patient 's pain and distension continued to worsen . at laparotomy the small bowel was decompressed to view the colon and to rule out further contributing pathology . a defunctioning transverse loop colostomy was performed without removing the stone to avert the immediate crisis , while minimizing morbidity and mortality . this would have hastened patients post - operative recovery , while resulting in a similar functional outcome . we believe this to be the first instance that an impacted gallstone has been left in situ post - operatively with a proximal loop colostomy used for symptomatic relief . there are various options now for retrieval of the stone , should this be necessary . the gallstone could be accessed directly via the colostomy or anus , and it may be possible to use lithotripsy to shatter and remove the stone without resorting to surgery . on the other hand , it could be left alone , as although fears remain that such a stone might erode through the wall or cause a localized abscess , decompression of the bowel has significantly reduced the chance of pressure necrosis and related complications .

we present a rare case of large bowel obstruction secondary to colonic gallstones in a frail nonagenarian . uniquely , the stone was impacted in the descending colon - sigmoid junction , in the absence of underlying bowel pathology distal to the stone . in light of worsening pain and distension after failed endoscopic treatment , the patient was treated with an emergency laparotomy . after an on - table dilemma , a proximal defunctioning loop colostomy was fashioned and the stone left in situ , with the eventual fate of the stone currently undecided . we also discuss alternative treatment options and explain the thought processes that lead to our decision .

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hailey - hailey disease ( hhd ) or familial benign chronic pemphigus first described in 1939 , is a rare autosomal dominant genodermatosis , which presents with recurrent vesicles , erythematous crusts and erosions in the areas subjected to friction , including , the neck and intertriginous areas . abnormalities in the tonofilament desmosome keratin complex results in marked acantholysis , giving the histological appearance of a dilapidated brick wall , which is pathognomonic of the disease . ultra violet b rays the treatment is often not satisfactory and hence , various modalities of treatment have been tried . we describe a case of hhd with a positive family history , in which various treatment modalities were tried without any benefit but responded well to thalidomide . a 30-year - old unmarried male presented with a history of recurrent painful fluid and pus filled lesions followed by painful erosions over the neck , axillae , trunk and groins of 15 years duration exacerbated over the past 10 - 15 days . he gave family history of similar disease in his father , paternal grandmother and paternal uncles . before coming to us , he had been treated with dapsone following which he developed agranulocytosis and dapsone was discontinued . several other treatment modalities including oral and topical antibiotics , corticosteroids were tried but resulted in only partial or temporary improvement . large macerated plaques studded with foul - smelling pus along with erosions , fissures , and crusts were present on the anterior and the lateral aspect of the neck , axillae , back , lower abdomen , pubic area , gluteal cleft , groins , upper medial thighs and scrotum [ figure 1 ] . erosions and crusts were seen on the glans with purulent foul smelling discharge in the prepucial sac , sparing rest of the penis . the skin biopsy specimen for histopathological reconfirmation of the diagnosis revealed focal suprabasilar clefting , few acantholytic cells , intercellular edema with dilapidated brick wall appearance which confirmed our diagnosis [ figures 2 and 3 ] . macerated plaques with erosions and crusts over the scrotum , glans penis and upper medial thighs focal suprabasal clefting and lacunae ( h and e , 10 ) suprabasalar clefting with few acantholytic cells , intercellular edema and dilapidated brick wall appearance ( h and e , 40 ) patient was started on intravenous ( iv ) betamethasone 4 mg , 8 h which was tapered off with the introduction of 40 mg of oral prednisolone , iv ceftriaxone 1 mg twice daily and later iv piperacillin - tazobactam based on pus culture and sensitivity reports along with a combination of fusidic acid and betamethasone for topical application . he continued to develop new lesions with the deterioration of his general condition and was febrile throughout . in spite of controlling the secondary infection , the vesicular eruptions persisted . therefore , he was started on oral thalidomide 100 mg three times a day and a combination of betamethasone and gentamycin for topical application . marked improvement was seen within a week of starting thalidomide [ figure 4 ] and hence we discontinued corticosteroid after rapid tapering of its dose and continued treating him with oral thalidomide 100 mg three times a day for one more week , which was then tapered off in 3 - 4 weeks and maintained on 50 mg daily . after 6 months of receiving 50 mg thalidomide , the drug was stopped in view of no recurrence of the lesions . he has improved well and comes to us for regular follow - up . mucosal involvement is unusual in hhd and has been very rarely reported and can involve oral , conjunctival , vaginal , or in very rare instances esophageal mucosa . our patient had oral , pharyngeal , and genital mucosal involvement , which were resistant to the symptomatic treatment . apart from the symptomatic therapy , drugs such as corticosteroids , dapsone , etretinate , methotrexate , cyclosporine , topical 5-fluorouracil , topical vitamin d analogs , topical zinc oxide , alefacept , psoralen plus ultraviolet a therapy and photodynamic therapy have been tried with varying results . as hhd is often recalcitrant to treatment , further options including invasive methods such as grenz ray therapy , carbon dioxide laser abrasion , erbium : yag laser ablation , dermabrasion , electron beam therapy , botulinum toxin and full - thickness excision of affected skin with repair by split - thickness grafting have been reported as useful in treatment of hhd . in the study conducted by galimberti et al . hhd is linked to mutations in the calcium - transporting atpase type 2c member 1 gene encoding the human secretory pathway ca / mn atpase . topical gentamicin was found to be very effective in inducing remission in a hhd patient carrying a premature stop mutation . it may be an important alternative in the treatment of hhd in patients not responding to the other modalities of treatment or when the conventional drugs are contraindicated . mucosal involvement is unusual in hailey - hailey disease ( hhd ) and has been very rarely reported . our patient had oral , pharyngeal , and genital mucosal involvement.thalidomide may be an important alternative in the treatment of hhd in patients not responding to the other modalities of treatment or when the conventional drugs are contraindicated . mucosal involvement is unusual in hailey - hailey disease ( hhd ) and has been very rarely reported . thalidomide may be an important alternative in the treatment of hhd in patients not responding to the other modalities of treatment or when the conventional drugs are contraindicated .

familial benign chronic pemphigus or hailey - hailey disease ( hhd ) is a rare autosomal dominant disorder characterized by the development of recurrent blisters and erosions in the intertriginous areas . various topical and systemic treatment options include corticosteroids , topical 5-fluorouracil , topical vitamin d analogs , topical zinc oxide , dapsone , psoralen plus ultraviolet a , systemic retinoids , cyclosporine , methotrexate , and photodynamic therapy . in recalcitrant cases , further options including , invasive methods such as grenz ray therapy , carbon dioxide laser abrasion , and erbium : yag laser ablation , dermabrasion , electron beam therapy , botulinum toxin , and full - thickness excision of affected skin with repair by split - thickness grafting have been reported as useful in treatment of hhd . we describe a case of hhd who was treated with several treatment modalities including antibiotics , corticosteroids , and dapsone earlier and when presented to us had a severe recalcitrant disease . thalidomide , as a modality of treatment has been successfully used in few cases earlier . our patient responded well to thalidomide .

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udp - glcua ( ammonium salt ; > 98% purity ) , and nad ( sodium salt ; 98% purity ) were obtained from sigma aldrich . purified preparations of wild - type hugdh and e161q mutant were obtained using reported procedures . both enzymes were produced as fusion proteins containing an n - terminal extension , which comprised a solubility enhancement tag , a streptavidin tag , and a tobacco etch virus protease cleavage site . the n - terminal extension was then removed , and the enzymes were further purified by gel filtration and anion - exchange chromatography . a 50 mm potassium phosphate buffer at pd 5.9 , 7.0 , 7.9 or 8.8 was used . starting concentrations were 15 mm nad , 2 mm udp - glc and 0.38 m wild - type hugdh or 15 m e161q . after addition of all components , the reactions were incubated at 25 c for 16 h. for determination of the solvent isotope effect , enzymatic conversions in h2o or d2o were performed in a beckman coulter du800 spectrophotometer using a 50 mm potassium phosphate buffer with ph / pd 7.5 . reaction velocity was measured by nadh absorption ( = 340 nm ) . all spectra were recorded on a bruker drx-600 avance spectrometer ( bruker , rheinstetten , germany ) at 600.13 mhz ( h ) . the h nmr spectra were measured at 298.2 k with presaturation ( 1.0 s ) and acquisition of 32k data points . after zero filling to 64k data points , spectra were performed with a range of 7200 hz . chemical shifts were referenced to external acetone ( h = 2.225 ppm ) . the reactions were directly made in a 5 mm high precision nmr sample tube ( promochem , wesel , germany ) to measure in situ h nmr spectra . samples contained 2 mm udp - glc , 15 mm nad , and 0.084 m wild - type hugdh or 33 m e161q , as well as 50 mm potassium phosphate buffer in d2o ( 0.70 ml , 99.9% d , pd 7.5 or 8.3 ) . 12 h in the magnet by recording up to 64 h nmr spectra in regular intervals . the topspin 3.0 software from bruker was used for processing the nmr spectra after data acquisition . for quantitative analysis of the nmr data , a correction value was subtracted from the integral values of each proton to account for background noise . udp - glcua ( ammonium salt ; > 98% purity ) , and nad ( sodium salt ; 98% purity ) were obtained from sigma aldrich . purified preparations of wild - type hugdh and e161q mutant were obtained using reported procedures . both enzymes were produced as fusion proteins containing an n - terminal extension , which comprised a solubility enhancement tag , a streptavidin tag , and a tobacco etch virus protease cleavage site . the n - terminal extension was then removed , and the enzymes were further purified by gel filtration and anion - exchange chromatography . full details of the purification protocol are given elsewhere . enzymatic assays were performed in 1 ml of d2o . a 50 mm potassium phosphate buffer at pd 5.9 , 7.0 , 7.9 or 8.8 was used . starting concentrations were 15 mm nad , 2 mm udp - glc and 0.38 m wild - type hugdh or 15 m e161q . after addition of all components , the reactions were incubated at 25 c for 16 h. for determination of the solvent isotope effect , enzymatic conversions in h2o or d2o were performed in a beckman coulter du800 spectrophotometer using a 50 mm potassium phosphate buffer with ph / pd 7.5 . reaction velocity was measured by nadh absorption ( = 340 nm ) . all spectra were recorded on a bruker drx-600 avance spectrometer ( bruker , rheinstetten , germany ) at 600.13 mhz ( h ) . the h nmr spectra were measured at 298.2 k with presaturation ( 1.0 s ) and acquisition of 32k data points . after zero filling to 64k data points , chemical shifts were referenced to external acetone ( h = 2.225 ppm ) . the reactions were directly made in a 5 mm high precision nmr sample tube ( promochem , wesel , germany ) to measure in situ h nmr spectra . samples contained 2 mm udp - glc , 15 mm nad , and 0.084 m wild - type hugdh or 33 m e161q , as well as 50 mm potassium phosphate buffer in d2o ( 0.70 ml , 99.9% d , pd 7.5 or 8.3 ) . 12 h in the magnet by recording up to 64 h nmr spectra in regular intervals . the topspin 3.0 software from bruker was used for processing the nmr spectra after data acquisition . for quantitative analysis of the nmr data , a correction value was subtracted from the integral values of each proton to account for background noise .

graphical abstract

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skin metastasis from a thyroid carcinoma is rarely a presenting feature of an underlying malignancy . subcutaneous metastasis from differentiated thyroid carcinoma ( dtc ) is a rare manifestation of disseminated disease . some of the authors believe that follicular carcinoma of the thyroid has a higher propensity to metastasize to the skin , followed by papillary carcinoma , then anaplastic carcinoma and finally medullary carcinoma . others believe that papillary carcinoma is the most common thyroid carcinoma metastasizing to the skin . all agree that the scalp is the most common site of thyroid carcinoma skin metastases . there are no previous reports of positron emission tomography / computed tomography ( pet / ct ) in patients with loin metastasis from an unknown primary and identified as papillary cancer thyroid . this was a case report of a 45-year - old male patient who presented with subcuataneous swelling in the left loin , which on biopsy showed metastatic papillary cancer . pet / ct showed an intense uptake in the subcutaneous soft - tissue lesion in the left loin [ figure 1 ] . a diagnosis of primary papillary carcinoma of thyroid with subcutaneous loin metastasis was made and he was advised total thyroidectomy and excision of metastasis . whole body fluorodeoxyglucose - positron emission tomography/ computed tomography ( pet / ct ) maximum intensity projection image ( a ) axial ct ( b ) pet ( c ) fused pet / ct ( d ) showed a intense uptake in the subcutaneous soft tissue lesion in the left loin axial ct ( a ) pet ( b ) fused pet / ct ( c ) showed a intense uptake in the right lobe thyroid nodule cutaneous metastasis from dtc is also a rare manifestation of thyroid cancer . a review on roughly 60 cases of dtc skin metastases , which have been documented in the literatures , stated that pc has a greater preponderance for skin metastases dermal lesions typically present as slowly growing erythematous or purple plaques or nodules , usually on the scalp , face , or neck . this may relate to local vascular factors essential for the highly complex nature of metastases . pet / ct is very useful in identifying unknown primary cancer from the metastatic lesions . there are reports of pet / ct in identifying occult papillary cancer in a thyroglossal cyst . however , 18 fluorine - fluorodeoxyglucose - pet / ct has a role in 131i - whole body scan negative patients with elevated thyroglobulin . there are reports of pet / ct in identifying muscle and scalp metastasis from a papillary thyroid cancer . this is the first case of identifying primary papillary cancer with subcutaneous metastasis in pet / ct . recognizing and understanding the clinical findings

differentiated thyroid cancer frequently metastasizes but generally spreads to regional cervical lymph nodes and , in advanced cases , to the lungs and/or skeleton . metastases to the skin / subcutaneous tissue are rare . we report 45-year - old male patient presented with a loin swelling which on biopsy showed a papillary carcinoma and referred for fluorodeoxyglucose - positron emission tomography / computed tomography ( fdg pet / ct ) to find out the primary disease . pet / ct showed abnormal fdg uptake within a loin metastasis and right lobe thyroid nodule . fine - needle aspiration from nodule showed papillary carcinoma . because thyroid cancer can rarely metastasize to the skin , attention should be given to that region during interpretation of the images . he was advised total thyroidectomy and metastasis excision .

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ectopia cordis is a rare congenital malformation in which the heart is located partially or totally outside the thoracic cavity . ectopia cordis may occur as an isolated malformation or it may be associated with body wall defects that affect the thorax , abdomen , or both . with the advances in the medical field and surgical technique , a 24-year - old , unbooked primigravida delivered spontaneously , a 34-week , male stillborn weighing 1,870 g at kasturba hospital , mgims , sevagram . there was no history of intake of any teratogens or exposure to unusual environment in antenatal period . an anterior thoracoabdominal defect with extrathoracic heart , a cleft sternum , and omphalocele were recognized at birth . the physical examination revealed an exposed heart totally outside of the thoracic cavity without pericardium protection . the abdominal wall defect that caused evisceration of liver , stomach , and the intestines [ figure 1 ] . other abnormal features included asymmetrical face with medial epicanthal folds , low set ears , micrognathia , asymmetrical bossing of the skull , and high arched palate . ectopia cordis is a very rare anomaly with an estimated prevalence of 0.079/10,000 births and may occur more frequently in females . it is related to the malformation of the anterior wall of the thorax , with an extrathoracic location of the heart . in 1958 , cantrell described this syndrome , which occurs sporadically , with variable degrees of expression . ectopia cordis can be classified into five types : 1 ) cervical , in which the heart is located in the neck with sternum that is usually intact ; 2 ) thoracocervical , in which the heart is partially in the cervical region , but the upper portion of the sternum is split ; 3 ) thoracic , in which the sternum is completely split or absent , and the heart lies partially or completely outside the thorax ; 4 ) thoracoabdominal , which usually accompanies cantrell 's syndrome ; and 5 ) abdominal , in which the heart passes through a defect in the diaphragm to enter the abdominal cavity . our case had thoracoabdominal type ectopia cordis in which the bifid sternum , extrathoracic heart , absence of parietal pericardium , and an omphalocele was present . the formation of the thoracic and abdominal walls is complete in the 9 week of pregnancy and of the heart in the 8 week . complete or incomplete failure of midline fusion at this embryonic stage can result in a variety of disorders ranging from isolated ectopia cordis to complete ventral evisceration . ventricular septal defect , atrial septal defect , tetralogy of fallot , and diverticulum of the ventricle are the most commonly encountered heart lesions . ectopia cordis has also been reported with other congenital anomalies such as abdominal wall defects , cranial and facial malformations , cleft lip and palate , anencephaly , hydrocephaly , neural tube defects , pulmonary hypoplasia , genitourinary malformation , gastrointestinal defect , and chromosomal abnormalities . the defect of the abdominal wall can range from simple diastasis to huge omphaloceles with bowel , liver , and heart . the ectopic heart may either simply bulge out of the chest or be entirely out of the chest . the diagnosis has been made as early as 17 weeks , but in some cases complicated by oligohydramnios , these cases may be missed entirely . the differential diagnosis includes isolated thoracic ectopia cordis , amniotic band syndrome , and body stalk anomalies . the key features for distinguishing these conditions is the position of abdominal wall defect in relation to the umbilical cord insertion , eviscerated organs , the presence or absence of membranes or bands , and associated anomalies . omphalocele in cantrell 's pentalogy usually involves a midline defect at the umbilical cord insertion . an eccentric large lateral defect and adherence of the placenta to the defect the presence of an unexplained ventral wall defect along with extremity deformity with an adherent band suggests amniotic band syndrome . the prenatal diagnosis is easily made with ultrasound by visualizing the heart outside the thoracic cavity . in view of the poor prognosis , the prognosis depends on the degree of the intracardiac involvement and associated malformations , as well as the degree to which the heart is exposed . attempts at surgical correction are already widely performed , with immediate covering of the heart and exposed abdominal contents using silastic prosthesis being recommended . additionally , a complete evaluation and correction of the intracardiac defects should be performed before closing the abdominal wall . in conclusion , ectopia cordis with omphalocele is a rare congenital malformation from fatal to nonfatal , therefore it must be adequately evaluated for appropriate prenatal and postnatal management .

a rare congenital defect in fusion of the anterior chest wall resulting in an extrathoracic location of the heart . cantrell 's pentalogy is a congenital anomaly resulting from embryologic development defect and consists of the following : a deficiency of the anterior diaphragm , a midline supraumbilical abdominal wall defect , a defect in the diaphragmatic pericardium , congenital intracardiac abnormalities , and a defect of the lower sternum . here we report a rare case of ectopic cordis with omphalocele .

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left ventricular thrombus ( lvt ) is one of the most common complications of myocardial infarction ( mi ) . the incidence of lvt in patients with acute anterior mis in the prethrombolytic era is ranged from 20% to 40% and with a non anterior acute myocardial infarction ( ami ) and the risk of lvt was < 5% . although controversial , in the contemporary era of routine early revascularization and more aggressive anticoagulation , the incidence of lvt complicating as an anterior ami is likely reduced and is currently estimated at 5 - 15% . the risk factors for the development of lvt are consistently irrespective of infarct treatment and include large infarct size , severe apical akinesia , or dyskinesia left ventricular ( lv ) aneurysm , and anterior mi . two - dimensional transthoracic echocardiography is the imaging modality used most often for assessing the presence , shape , and size of an lv mural thrombus with an excellent specificity of 85 - 90% and sensitivity of 95% . here , we report a case of 40-year - old male patient who is presented in emergency department with the complaint of substernal chest pain radiating to left arm and back associated with sweating for the last 1 day , there was no history of dyspnea , palpitation , any limb weakness , or any history suggestive of transient ischemic attack and peripheral embolization . his 12-lead electrocardiogram was suggestive of inferior wall mi [ figure 1 ] . his total leukocyte and eosinophil counts were normal , prothrombin time / international normalized ratio and activated partial thromboplastin time were normal , and other tests for hypercoagulable states were planned for the follow - up evaluation . a transthoracic echocardiogram was performed bedside which revealed hypokinesia of basal , mid inferior , and inferoseptal wall [ figure 2 and video 1 ] . surprisingly , it also revealed a mobile mass which is the most probably thrombus attached to hypokinetic inferobasal septum just near the lv outflow tract ( lvot ) [ figure 3 and video 2 ] . considering the possibility that this mass was high risk for embolism , we planned for coronary angiogram followed by the surgical extraction of possible thrombus . however , unfortunately , despite the proper counseling and explanation of the risk of embolism , the patient refused for further intervention and got discharged against medical advice . small arrows showing hypokinesia of basal inferior septum , large arrow indicates left ventricle probable thrombus apical four chambers view thrombi formation at basal interventricular septum near lvot is extremely rare as it is a region of high - velocity blood flow . traditionally , the causes of lvt formation after acute st - segment elevation mi include segmental dysfunction of the infracted myocardium resulting in the stasis of blood , endocardial tissue inflammation that provides a thrombogenic surface and a hypercoagulable state . the higher mortality has been reported in patients with lv thrombi after infarction , especially when these develop within the first 48 h after infarction . the treatment for cardiac mass is a prompt surgical resection of the mass with the patients placed on cardiopulmonary bypass . therefore , better understanding of the circumstances in which lv thrombosis occurs may influence the patient management . in our case , thrombus formed at the very unusual site and could lead to dreaded complication for the patient . the possible etiology of thrombus formation , in our case , is hypokinesia of basal septum due to mi , but the presence of a subtle septal rupture which is not detectable on echocardiography could not be ruled out .

left ventricular ( lv ) thrombus formation is a frequent complication in patients with acute anterior myocardial infarction ( mi ) . its incidence is lower with inferior wall mi . risk factors for the development of lv thrombus are consistently irrespective of infarct treatment and include large infarct size , severe apical akinesia or dyskinesia lv aneurysm , and anterior mi .

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bronchial atresia resulting from a localized defect in normal bronchopulmonary embryogenesis is a rare disease . it can produce emphysematous changes in the affected pulmonary segment or lobe with or without dyspnea and/or episodic pulmonary infection . we herein report a case of bronchial atresia associated with pneumothorax which was successfully treated with lobectomy . a 32-yr - old korean male patient was admitted to inha university hospital , incheon , korea due to dyspnea and right chest pain for 1 day . on physical examination , the breath sound in the right lung fields was decreased without shifting of the maximal point of the cardiac impulse . he had a history of the right pneumothorax one and a half years ago , which was treated with tube thoracostomy . the posteroanterior chest radiograph revealed increased radiolucency along with overinflated lung parenchyma and sparse vasculature in the upper half of the right lung . the chest ct taken in the state of full expansion of the right lung after tube thoracostomy showed a branching soft tissue density in the region of the posterior segment of the right upper lobe . the orifice of the posterior segmental bronchus was visualized but the orifice of the subsegmental branch of the posterior segmental bronchus could not be visualized separate from the origin ( fig . 2 ) . there were no endobronchial lesions in the bronchial tree on the bronchoscope and each orifice of the segmental bronchi of the right lung was seen normal . his forced expiratory volume at 1-sec ( fev1 ) was 3.49 l ( 91% ) and forced vital capacity ( fvc ) was 4.57 l ( 100% ) . there was a localized emphysematous change in the posterior segmental area of the right upper lobe with the apical pleural adhesion and the remaining lungs were normal . the pathological findings of the resected right upper lobe showed overinflation of the posterior segment . there were no obstructed lesions of the orifices of the three segmental bronchi of the right upper lobe . however , one of the subsegmental branch of the posterior segmental bronchus was obstructed and there was a 2.51.51.5 cm sized cystic mass containing brownish mucus material at the distal portion of the obstructed subsegmental bronchus . microscopically the distal air spaces of the atretic segmental bronchus showed overinflation only . however the foci of the subpleural bullae in the overinflated segment were observed ( fig . bronchial atresia is a rare disease , which develops due to the failure of embryogenesis of the segmental or lobar bronchial tree . since the first report of bronchial atresia by ramsay et al . in 1953 , there have been many illustrations and reports about bronchial atresia ( 1 - 8 ) . according to the reports , most of the patients with bronchial atresia were asymptomatic and it was diagnosed incidentally in the second or third decade of life on routine chest radiography ( 2 - 4 ) . the common radiographic findings of bronchial atresia are hyperinflation of the involved lung parenchyma and collapse of the affected lobe with a radioopaque extrahilar mass with mucocele in patients who had pulmonary symptoms such as fever , cough , and shortness of breath due to recurrent pulmonary infection or overinflation of the involved lung parenchyme ( 3 , 4 , 6 , 8) . however , bronchial atresia associated with pneumothorax is extremely rare in spite of overinflation of the involved lung parenchyma . we report a case of bronchial atresia in the subsegmental branch of the posterior segmental bronchus of the right upper lobe associated with mucocele and recurrent spontaneous pneumothorax , which was treated with right upper lobectomy . the resected specimen showed atresia of the subsegmental branch of the posterior segmental bronchus of the right upper lobe with hyperinflated lung with subpleural bullae . the cause of pneumothorax was thought to be due to the rupture of the bulla in the hyperinflated lung segment . the exact mechanism of bulla formation of the affected lung parenchyma could not be proved . however , we think the bullous change have been resulted from mechanical stress to the alveoli wall from hyperinflation of the lung parenchyma distal to the atretic bronchus due to aeration by check - valve mechnanism through the collateral channels of the interalveolar pores of kohn and bronchoalveolar channels of lambert .

a 32-yr - old male patient with recurrent pneumothorax associated with bronchial atresia of the subsegmental branch of the posterior segmental bronchus of the right upper lobe was successfully treated with right upper lobectomy . before surgery , the bronchial atresia with pneumothorax was suspected on the chest radiograph and ct scans , which showed the findings of bronchocele with localized hyperinflation of the right upper lobe . the examination of surgical specimen from the resected right upper lobe suggests that the cause of the recurrent pneumothorax was the rupture of the subpleural bullae in the hyperinflated lung segment distal to the atretic bronchus .

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aspergillosis is the most common fungal infection of the paranasal sinuses and it usually occurs unilaterally in maxillary sinus . on the other hand , transverse maxillary deficiency ( tmd ) is one of the most common skeletal dysplasias observed in clinical practice . it can be treated with several techniques such as slow orthodontic expansion , rapid palatal expansion , and surgically assisted rapid palatal expansion ( sarpe ) , and the recommended technique for adult patients is sarpe because of limited osteogenic activity of palatal suture . the use of sarpe to treat tmd decreases adverse effects of orthodontic expansion such as lateral tipping of posterior teeth , extrusion , periodontal membrane compression , buccal root resorption , alveolar bone bending , fenestration of the buccal cortex , palatal tissue necrosis , inability to open the midpalatal suture , pain , and instability of the expansion . although sarpe is a relatively easy and an effective operation , complication possibility due to technical sensitivity of surgical approach and patient 's systemic condition must be considered . in this case report , perforation - related fistula formation on inferior meatus and unilateral aspergillosis infection in maxillary sinus associated with sarpe , treated with functional endoscopic sinus surgery ( fess ) , were evaluated . a 32-year - old systemically healthy woman with tmd was referred from the orthodontics department . the patient was operated under general anesthesia with nasal endotracheal intubation . before the surgical procedure , expansion device was activated . following the full - thickness sulcular incision on the deepest level of the vestibular sulcus incision , the lateral surface of the maxilla was exposed with subperiosteal dissection . nasal mucosa was elevated from the lateral nasal wall without any perforation , and bilateral corticotomy starting from the pyriform aperture to the pterygomaxillary fissure was performed . the medial walls of maxillary sinuses were separated bilaterally using guided osteotomes , and the palatal suture was separated using sharp chisel osteotome . the incision was closed primarily , and anterior nasal packs ( merocel standard dressing ) were applied . the patient was discharged on the same day , and the 1 week of healing period was uneventful . the patient consulted an ent specialist and computed tomography revealed that the left middle meatus was congested with radiopaque substance [ figure 1 ] . besides , endoscopic sinus examination showed that there was pus drainage from maxillary sinus to inferior meatus through fistula [ figure 2 ] , and augmented amoxicillin with clavulanic acid ( augmentin , 1 g ) was prescribed for 2 weeks to control sinusitis . computed tomography imaging of congested ostium and radiopaque appearance defluxion from fistula after 2 weeks , a granulation tissue in the maxillary sinus was observed during the endoscopic examination [ figure 3 ] , and fess was performed for decontamination of the maxillary sinus and correction of ostium function . augmented amoxicillin with clavulanic acid ( augmentin , 1 g ) was prescribed for 2 weeks again after fess , and histopathological examination of the substance removed from the sinus revealed aspergillosis [ figure 4a c ] . granulation formation ( a ) middle meatal antrostomy , ( b ) removal of substance located in the maxillary sinus , ( c ) postoperative appearance of the middle meatus after 3 weeks , it was observed that the ostium was functioning and there was no sign of aspergillosis . in 3 months correction of tmd in adult patients is more challenging because of changes in osseous articulations of the maxilla with adjoining bones . procedures described for the correction of tmd have conventionally been grouped into two categories as segmenting the maxilla during the le fort 1 osteotomy in a widened transverse dimension and sarpe . however , sarpe has become a common procedure and it has been considered as the procedure which has the lowest morbidity incidence , especially when compared with other orthognathic surgery procedures . sarpe allows clinicians to achieve satisfactory maxillary expansion in a skeletally mature patient and it decreases adverse effects of orthodontic expansion . although sarpe is a relatively simple procedure among other orthognathic surgery techniques , complications related with surgical technique and systemic condition of the patient must be considered . in this case , fistula formation between the maxillary sinus and the inferior meatus occurred during osteotomy step of sarpe procedure , and the alteration of the sinus ventilation was complicated by the presence of aspergillosis . it is well - known data that the use of wide broad spectrum antibiotics in a long period can cause fungal infection . the middle meatus dysfunction and the operation trauma are other reasons of aspergillosis formation in this case . although potential association between aspergillosis and sarpe was not described before in literature , it must be noted that sarpe causes perforation and fistula formation between the nasal cavity and maxillary sinuses . despite the frequent use of the procedure , only limited data on the prevalence of postoperative complications after sarpe are available in literature . on the other hand , some severe and unusual complications have been reported . it should be noted that fistula formation and meatus dysfunction related with sarpe operation cause fungal infection development .

surgically assisted rapid palatal expansion ( sarpe ) is one of the most common orthognathic surgery operations for the treatment of maxillary transverse deficiencies . although this operation is considered technically simple and has low complication rate , predisposing factors can complicate the postoperative period . in this case report , fistula formation and aspergillosis after sarpe operation were presented .

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a 68-year - old male patient visited konkuk university hospital due to epigastric pain lasting 2 to 3 seconds 2 months before hospitalization . according to his anamnesis , he was taking 50 mg of atenolol because he had been diagnosed with hypertension 2 years before . he had been diagnosed with esophageal diverticulum 10 years before ; since then he had experienced no symptoms . he underwent a cardiac computed tomography ( ct ) scan 3 weeks prior to hospitalization . the ct scan showed that mild stenosis ( 20% to 30% ) had formed in left anterior descending artery , left circumflex artery , and right coronary artery . he underwent gastroesophageal endoscopy ; 5 cm of diverticulum was found 20 cm from the incisor tooth ( fig . 1 ) . there were no other findings except for erosive gastritis in the antrum of the stomach . the esophagography 2 weeks prior to the hospitalization showed that there was 10 cm of diverticulum projecting to anterolateral side ; killian - jamieson diverticulum ( kjd ) was considered ( fig . although the location of the diverticulum on the esophagogram was right side , we decided left cervical approach for surgeon 's convenience . left cervical incision was conducted under general anesthesia and the cervical esophagus was exposed following dissection along the sternocleidomastoid muscle . diverticulum ( 105 cm sized ) was found with a wide base and which contained a small amount of necrotic tissue ( fig . the diverticulum adhered to circumjacent tissues ; in particular , it strongly adhered to the prevertebral fascia in the rear of the trachea . cervical esophagus proximal to the diverticulum was dissected cautiously and looped with a silastic drain . the diverticulum was excised with a ta 60 stapler ( ethicon endo - surgery , cincinnati , oh , usa ) . esophageal myotomy of about 3 cm was conducted along the distal part of the esophagus after the excision of the diverticulum . reinforcement sutures were inserted with 3 - 0 silk along the excision area of diverticulum . the esophagography on the fourth day after the surgery showed that there were not abnormalities such as leakage or stenosis ; therefore , dietary treatment was initiated . the patient was discharged from konkuk university hospital on the sixth day after the surgery . at the time of discharge follow - up observation has been performed for 6 months , during which the patient has not shown any abnormalities such as diverticulum relapse , dysphagia , or stenosis . kjd is a rare form of esophageal diverticulum which appears through the killian 's dehiscence , a mucosal protrusion below the cricopharyngeal muscle . kjd is similar to zenker 's diverticulum ( zd ) due to the protrusion of esophageal mucosa . kjd is rare in that the incidence of kjd is a fourth of that of zd . the two diseases have similar symptoms ( e.g. , dysphagia , coughing , and chest pain ) . however , according to previous studies , kjd has more non - specific symptoms than zd . location is a standard for distinguishing them : zd occurs mainly in the rear of the esophagus in the upper cricopharyngeal muscle , and kjd occurs mainly in the front or side of the esophagus 2 cm away from the lower cricopharyngeal muscle . the two diseases , zd and kjd , have been observed simultaneously . in rare cases , because of its symptom or greater size , endoscopic treatment and surgical treatment are used for kjd . generally , endoscopic treatment is considered preferable in treating zenker 's diverticula smaller than 3 cm . endoscopic treatment has the possibility of occluded view when there is food or a foreign body in the diverticulum . the treatment of the kjd is more closely adjacent to the recurrent laryngeal nerves than zd . for kjd treatments that do not come into contact with the recurrent nerves , treatments other than endoscopic treatments are preferable . according to the previous studies , the safety of endoscopic treatment has not been established for kjd , due largely to the rarity of cases , and for zd the recurrence rate of endoscopic treatment is 10 times higher than that of surgical treatment . furthermore , myotomy should be adopted as a treatment for kjd , since its treatment is closely related to the prevention of the recurrence of zd from the perspective of the features of diverticular disease . in conclusion , konkuk university hospital experienced the successful treatment of a case of kjd that had been accompanied by rare symptom and discussed the result together with the review of the relevant literary works .

killian - jamieson diverticulum is a rare diverticular disease . this disease differs from zenker 's diverticulum in its location and mechanism . various treatment modality have been attempted , but traditional surgical treatment has been recommended for a symptomatic killian - jamieson diverticulum due to the concern of possible nerve injury . we performed surgical treatment by cervical incision . we report here on a case of killian - jamieson diverticulum and we briefly review the relevant literature .

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pyoderma gangrenosusm ( pg ) is a chronic , rare , inflammatory cutaneous disorder and is manifested by the development of painful ulcers , bulla , pustules and rarely vegetating lesions and histologically by predominantly neutrophilic infiltration . we report a case of severe pg in a girl since her 4 months of age . the difficulty in diagnosis and methodical approach in such cases is highlighted . a 6-month - old hindu girl presented with progressive , extensive , and painful ulcers since her 4 months of age . ulcers developed from erythematous papules and vesicles , had purple red undermined margin , raw or crusted surface , merged with other ulcers in the neighborhood and formed large ( even > 8 cm ) lesions with annular , polycyclic or crescent shape . they were distributed over scalp , face , ear , trunk ( less over anterior trunk ) , buttocks , thigh , legs , dorsum of hands and feet without any mucosal involvement [ figure 1 ] . ( a ) face , ( b ) arm , ( c ) dorsum of hand , ( d ) leg , ( e ) thigh , ( f ) back , ( g ) encircled site where intradermal normal saline was injected , ( h ) same site after 48 h showing pustulation ( positive pathergy test ) the child was playful with normal physical and intellectual growth . there was mild fever , moderate pallor without any cyanosis , clubbing , organomegaly , lymphadenopathy , or joint abnormality . pustule developed following intradermal injection of normal saline on normal skin ( positive pathergy test ) [ figure 1 ( g , h ) ] . there was low hemoglobin ( 8.9 gm / dl ) , leucocytosis ( 22,600/cmm ) , neutrophilia ( 70% ) , and elevated sedimentation rate ( 69 mmhg ) . chest x - ray , mantoux test , dna - pcr for tuberculosis , immunoglobulin level , ra factor , ana ( hep-2 cell ) , vdrl , c - anca , hiv- elisa , pus culture , and colonoscopy of rectal mucosa revealed no abnormality . histopathology of the skin biopsies with h and e stain from the margin of the ulcer from two different sites showed epidermal ulceration and dense dermoepidermal collection of inflammatory exudates consisting predominantly of neutrophils with occasional multinucleated giant cells [ figure 2 ] . one of the biopsies also showed foci of granulomatous reaction [ figure 2 , inset ] . z - n stain ( for afb ) and pas stain ( for fungus ) were negative . photomicrograph showing ulceration of epidermis and collection of inflammatory exudates along with occasional giant cells ( h and e , 100 ) . inset showing ill formed granuloma with giant cells ( h and e , 400 ) it was diagnosed as a case of pyoderma gangrenosum . the patient responded satisfactorily to oral prednisolone ( 2 mg / kg / day ) . however , there were signs of relapse with dose less than 1 mg / kg / day . at that time , the patient became irregular in follow - up and finally lost to follow up . in most of the cases , pg is associated with some systemic diseases like inflammatory bowel diseases ( ibd ) , rheumatoid arthritis , myeloproliferative disease , etc . extensive distribution of the disease was unusual for an infant with pg who generally have ulcers on head and buttocks . onset at 4 months of age was extremely rare and possibly not reported so far . due to much atypicality , diagnosis was difficult and many possibilities were considered like pg , tuberculous , atypical mycobacterial infection , fungal , malignant and vasculitic ulcers , wegener 's granulomatosis , sweet 's syndrome , and epidermolysis bullosa . violaceous undermined margin with erythematous halo , pain , characteristic histological appearance and positive pathergy test were helpful for diagnosis . multiple site colonoscopic biopsies from even normal rectal mucosa could have increased the diagnostic yield for any subclinical evidence of ibd . the case

a female child developed multiple , progressive , therapy - resistant , painful large ulcers , vesicles , and pustules since her 4 months of age . the ulcers were large , some even measured more than 8 cm ; most had violaceous undermined margin with surrounding erythematous halo , raw and crusted surface and were distributed extensively over scalp , face , ear , trunk , buttocks , thigh , legs , dorsum of hands , and feet without any mucosal involvement . after detail clinical examination and investigation , it was diagnosed as a case of pyoderma gangrenosum . extensive search did not reveal any systemic abnormality or detect any infective etiology . the case highlights the problems of diagnosis of multiple ulcers at very early age .

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they are congenital benign tumor accounting for 15 - 20 % of intraventricular mass but only about 1% of intracranial ones ( 1 - 3 ) . they can be diagnosed at any age but usually become symptomatic in the third to sixth decades and more common in men than women . they usually found incidentally and are asymptomatic ; but in some instances may associate with rapid neurologic deterioration , herniation , and sudden death . so , recognition of this rare but important diagnosis may result in decreasing mortality ( 4 ) . in this report , we presented a 13-year - old boy with complaint of two times drop attack and final diagnosis of colloid cyst in the third brain ventricle . a 13-year - old boy was brought to the emergency department ( ed ) with complaint of two times drop attack . the patient mentioned that he felt sudden weakness in both lower limbs , which led to drop . these attacks were happened about 4 hours before admission and he did not have any same experience previously . he did not have complaint of nausea , vomiting , headache , vertigo , blurred vision , or palpitation . the subject did not have any known structural or congenital heart disease , but suffered from asthma and used salbutamol spray irregularly . the patient did not have trauma history and there was no positive history of any known medical illness in his parents or closed relatives . on arrival , he had 36.9c axillary temperature , 16/minute respiratory rate , 90/minute pulse rate , 120/80 mmhg blood pressure , and 96% oxygen saturation at room air . on physical examination , he did not have focal neurologic findings or even paresthesia or paraplegia . general examination of head and neck , chest , abdomen , and limbs did not reveal any positive findings . following the evaluation process , a brain computed tomography ( ct ) was performed ( figure-1 ) . a hyperdense round lesion was seen in the third ventricle consequently caused that the corresponding physician requested a neurologic consultation in the ed . finally , the brain magnetic resonance imaging ( mri ) confirmed the diagnosis of third ventricle colloid cyst and the patient was underwent surgery and discharged without any problem ( figure 2 ) . the colloid cysts commonly settle near the foramen of monro in the anterior third ventricle and so may encounter with drainage of the cerebrospinal fluid ( csf ) ( 3 ) . since even a small lesion can block the mentioned foramen , these cysts may result in hydrocephalus and increase the intra cranial pressure ( 5 ) . increased intracranial pressure can be manifested with headache described as severe and intermittent , with short duration , usually located frontally . in contrast with usual headaches , secondary to intracranial tumors , the colloid cyst induced headache can be relieved by lying down ( 4 ) . other symptoms include drop attacks , gait abnormalities , progressive dementia , and transient loss of consciousness . in children , the most common symptoms are nausea , vomiting , headache , diplopia , and papilledema ( 6 ) . the classic clinical description of intermittent headaches and drop attacks occurs in only one - third of patients . sudden obstruction of the ventricular system and following rapid rising of intracranial pressure can lead to herniation and rarely sudden death ( 7 , 8) . colloid cysts size varies from 3 - 40 millimeters in diameter , but the size do not related to their symptoms or outcome , as even small ones may lead to sudden death ( 9 ) . colloid cyst is usually diagnosed by non - contrast computed tomography ( ct ) as an oval or rounded hyperdense mass on the anterior aspect of the third ventricle . they may occasionally be hypodense or isodense to the brain , or found in other areas of the brain . colloid cysts have different manifestation on mri . despite their variable signal characteristics , their location and shape help to the correct preoperative diagnosis in most patients ( 6 ) . half of the cases are hyperintense on t1-weighted mri images and hypointense on t2-weighted mri images respected to brain . isointense cysts are not easily identified on mri , and in such instances ct scan is more useful ( 9 , 10 ) . small asymptomatic colloid cyst can be considered for close follow up by serial examinations and neuroimaging ( 11 ) . there is also the rare report of spontaneous resolving of the third ventricle colloid cyst ( 12 , 13 ) . all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors .

colloid cysts are mucous - filled masses with an outer fibrous layer . these cysts are rare developmental malformation and not a true neoplasm . they usually found incidentally and are asymptomatic ; but in some cases may associate with rapid neurologic deterioration , herniation , and sudden death . recognition of this rare but important diagnosis may result in decreasing mortality . in this report , we presented a 13-year - old boy with complaint of two times drop attack and final diagnosis of colloid cyst in the third brain ventricle .

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psoriasis is a common chronic inflammatory skin , nails , and joints disease related to the immune system by periods of exacerbations and remissions . it is characterized by thick end , erythematous , and scaling lesions , which affects about 2 to 4 percent of the general population . the disease occurs equally in both sexes and the most common form of the disease is psoriasis vulgaris . the etiology is unknown but genetic and environmental factors , immune system disorders , and gastrointestinal dysfunction appear to be responsible . the aim of this study is to compare psoriasis and ghooba clinical manifestations and introduce medical treatment of this disease based on authentic books of traditional medicine . this study is a qualitative literature review based on reliable sources of traditional medicine , such as canon of medicine , makhzan - ul - adwiah , qrabadyne kabir , zakhireh - ye khwarazm shahi , tib - e - akbari and exir - e - azam . the causes of disease are poor performance of the liver and spleen and stomach , as well as excessive consumption of foods such as beef and veal , eggplant and fish . several local treatments such as wheat germ oil , flaxseed oil , black seed oil , and violet oil were recommended . psoriasis is a chronic , debilitating physical , mental , and sexual disease for which genetic , environmental and immunological factors are recommended for its etiology . this problem could be treated by the oral and topical medications symptomatically ; however , major side effects are associated with recent treatments . change in lifestyle , prevention issues , as well as herbal therapy are recommended for the treatment of psoriasis in traditional medicine .

background : psoriasis is a common chronic inflammatory skin , nails , and joints disease related to the immune system by periods of exacerbations and remissions . it is characterized by thick end , erythematous , and scaling lesions , which affects about 2 to 4 percent of the general population . the disease occurs equally in both sexes and the most common form of the disease is psoriasis vulgaris . the etiology is unknown but genetic and environmental factors , immune system disorders , and gastrointestinal dysfunction appear to be responsible . the aim of this study is to compare psoriasis and ghooba clinical manifestations and introduce medical treatment of this disease based on authentic books of traditional medicine.methods:this study is a qualitative literature review based on reliable sources of traditional medicine , such as canon of medicine , makhzan - ul - adwiah , qrabadyne kabir , zakhireh - ye khwarazm shahi , tib - e - akbari and exir-e-azam.results:probably , in traditional medicine , the most similar disease to psoriasis is ghooba . that is scaly lesion concomitant with itching and articular pain in most cases . the causes of disease are poor performance of the liver and spleen and stomach , as well as excessive consumption of foods such as beef and veal , eggplant and fish . several local treatments such as wheat germ oil , flaxseed oil , black seed oil , and violet oil were recommended.conclusion:psoriasis is a chronic , debilitating physical , mental , and sexual disease for which genetic , environmental and immunological factors are recommended for its etiology . this problem could be treated by the oral and topical medications symptomatically ; however , major side effects are associated with recent treatments . change in lifestyle , prevention issues , as well as herbal therapy are recommended for the treatment of psoriasis in traditional medicine .

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dd , caused by mutations in the er ca atpase atp2a2 ( sakuntabhai , et al . , 1999 ) , is an uncommon ( 1:30,000 ) blistering skin disease . patients with dd suffer from impaired cell - to - cell adhesion , defective keratinocyte differentiation , and non - physiologic keratinocyte apoptosis . histologically , dd manifests with suprabasal clefting in the epidermis , acantholysis , rounded dyskeratotic keratinocytes ( corps ronds ) , hyperkeratosis and parakeratotic keratinocytes in the stratum corneum ( grains ) . current treatments , such as retinoids , do not ameliorate the underlying defect in er ca sequestration , and are ineffective for many patients . this report , by savignac et al ( editor , please add reference ) , advances our understanding of dd in several important ways . first , it illustrates how er stress impairs the formation of both adherens junctions and desmosomes , contributing to dd pathogenesis . second , it expands our understanding of how er ca signaling may control , not only keratinocyte growth and differentiation , but also keratinocyte cell - to - cell adhesion . defects in desmoplakin redistribution have been associated with the impaired cell - to - cell adhesion seen in dd ( dhitavat , et al . , 2003 , defective desmoplakin redistribution after serca2 ca depletion is mediated by protein kinase c alpha ( pkcalpha ) ( hobbs , et al . , 2011 ) . pkcalpha also may act on desmoplakin to direct the hyperadhesive desmosomal state ( hobbs and green , 2012 ) , rearrange desmosome components during wound healing ( garrod , 2013 ) , and modulate desmosomal susceptibility to autoimmune attack in pemphigus vulgaris ( cirillo , et al . , more recently , cell - to - cell adhesion defects in dd also have been associated with defects in e - cadherin redistribution ( celli , a. , et al . , 2011 ) . because both desmoplakin and e - cadherin have been shown to have signaling as well as structural roles ( kowalczyk and green , 2013 , tu , et al . , 2012 ) , it is likely that interactions among adhesion components involve multiple feedback loops between each other and the serca2-controlled er ca store . mild and self - limited er stress , due to transient release and refill of er ca stores , is an important physiologic signal for epidermal permeability barrier repair and antimicrobial peptide synthesis ( celli , a. , et al . , 2011 , park , et al . , 2011 ) . once er ca depletion passes a critical threshold , the er unfolded protein response ( upr ) is triggered , and apoptotic mechanisms are initiated in many cell types ( oakes , et al . , 2003 ) . this report identifies er stress , induced by er ca depletion due to serca2 dysfunction , as an important contributor to dd pathogenesis . finally , this report demonstrates that treatment of dd keratinocytes with miglustat improves desmoplakin and e - cadherin redistribution and improves ( although it does not normalize ) cell - to - cell adhesion . the authors propose that miglustat acts as a chaperone that allows adhesion molecules to escape from the er stress - induced upr , thus enabling them to reach the plasma membrane and form adherens junctions and desmosomes . miglustat , used clinically for gaucher disease , also acts to inhibit glucosylceramide synthase ( reviewed in venier and igdoura ( venier and igdoura , 2012 ) ) , and an additional potential therapeutic pathway may be through its modulation of the ceramide / sphingolipid pathway previous described in dd pathogenesis ( celli , a , et al . , 2012 ) . lastly , since glucosylceramide synthesis is required for epidermal permeability maintenance ( jennemann , et al . , 2007 ) , some caution should be used in extrapolating these results from monolayer keratinocytes to a multilayered epidermis or to patients . as the authors note , however , therapeutic options for dd are limited , and miglustat may be the first in a series of agents that treat dd by facilitating redistribution of adhesion molecules to the plasma membrane .

darier 's disease ( dd ) is caused by mutations in the endoplasmic reticulum ( er ) ca2 + atpase atp2a2 ( protein serca2 ) . current treatment modalities are ineffective for many patients . this report shows that impaired serca2 function , both in dd keratinocytes and in normal keratinocytes treated with the serca2-inhibitor thapsigargin , depletes er ca2 + stores , leading to constitutive er stress and increased sensitivity to er stressors . er stress , in turn , leads to abnormal cell - to - cell adhesion via impaired redistribution of desmoplakin , desmoglein 3 , desmocollin 3 and e - cadherin to the plasma membrane . this report illustrates how er ca2 + depletion and the resulting er stress are central to the pathogenesis of the disease . additionally , the authors introduce a possible new therapeutic agent , miglustat .

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metronidazole , a nitroimidazole antimicrobial agent is widely used in the treatment of anerobic and protozoal infections for more than three decades . common side effects are nausea , vomiting , abdominal discomfort , headache , and metallic taste . neurological effects such as ataxia , dizziness , peripheral neuropathy , and seizures were also reported . we report a rare case of metronidazole - induced encephalopathy ( mie ) in order to create an awareness of this unusual entity among practitioners . a 39-year - old male without any comorbidities was brought to the emergency department for acute onset of slurring of speech , generalized weakness , and unsteadiness . he was unable to button his shirt , and turn a doorknob due to clumsiness of hands and fingers for the past 24 hours . four days prior to this admission , he complained of numbness and tingling sensation of toes and dorsum of both feet . recently , he was treated for amebic liver abscess with ultrasound - guided aspiration and was given tablet metronidazole 800 mg three times a day for 2 weeks . since repeat ultrasound revealed re - accumulation of liver abscess after 2 weeks , he was advised to continue metronidazole 800 mg three times a day orally for 2 more weeks . thus , he had taken 67.2 grams of tablet metronidazole over a period of 28 days . neurologic examination revealed the patient was conscious but confused , with dysarthria , nystagmus , dysmetria on finger - to - nose test , positive romberg 's sign ; graded sensory loss to pain , temperature , touch , and proprioception over distal lower and upper extremities in a stocking and glove type , and impaired joint position and vibration sense . clinical assessment of cranial nerve , muscular system , deep tendon reflexes , and gait was normal with absent babinski sign . his hematological , metabolic panel , thyroid profile , cerebrospinal fluid ( csf ) analysis , viral markers , arterial blood gas , ammonia levels , vitamin b1 , b12 , and folate levels were within normal limits but for mild derangement of liver function . his magnetic resonance imaging ( mri ) brain revealed symmetrical areas of altered signal intensity , appearing hyperintense on t2w and fluid - attenuated inversion recovery ( flair ) images , and involving the dentate nuclei and splenium of the corpus callosum . there was an evidence of diffusion restriction on diffusion - weighted / apparent diffusion coefficient mapping without evidences of hemorrhage or infarct . imaging findings were in favor of metronidazole toxicity , which was supported by the prolonged history of metronidazole intake . moreover , his symptoms disappeared on third day after discontinuation of metronidazole , and mri 4 months later showed resolution of the earlier described signal changes . mie usually occurs at doses exceeding a total of 50 grams / month or 1.5 to 2 grams / day . although the exact mechanisms are unknown , the possible mechanisms with experimental evidences are furnished . furthermore , cerebellum of rats has been shown to uptake carbon labeled metronidazole . in vitro , metronidazole incorporated into thiamine analogs , inhibits the phosphorylation of thiamine , thereby antagonizing vitamin b1 effect . radiolabelled metronidazole binds ribonucleic acid ( rna ) in a significant manner , and inhibits neuronal protein synthesis and facilitates degeneration . catecholamine neurotransmitters are oxidized by metronidazole derivatives to produce semiquinone and nito anion radicals which are neurotoxic . the case is presented so as to facilitate practitioners to recognize the symptoms and signs of metronidazole toxicity , and consider them in their differential diagnosis . it is worth to remember the potential neurological abnormalities and imaging findings of this entity , as this agent is frequently prescribed and used in clinical practice .

encephalopathy associated with metronidazole administration is an uncommon but potentially reversible disease and depends on the cumulative metronidazole dose , and most patients with this condition recover rapidly after discontinuation of therapy . we present a case as well as a review of the literature regarding this rare but serious adverse event .

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to determine the prevalence and clinical characteristics of hbov , we investigated the presence of this virus in children with respiratory tract infection in our region ( gipuzkoa , basque country , spain ) . among the first patients in whom hbov was detected in nasopharyngeal aspirates , we found two 12-month - old children with diarrhea in addition to respiratory symptoms . because animal parvoviruses are frequently associated with enteritis in young animals ( 6 ) , we investigated the presence of hbov in the diarrheal feces of both children . hbov was detected in both samples , and no other intestinal pathogens were identified . to rule out the possibility that this result could have been due to fecal contamination resulting from swallowing respiratory secretions , and to determine whether the gastrointestinal tract is affected by this new respiratory virus , we studied its presence in patient feces in 527 episodes of acute gastroenteritis , unrelated to respiratory infection , in children <3 years of age , mainly from nonhospital centers ( ambulatory clinics ) . viral dna and rna were obtained from nasopharyngeal aspirates and stool specimens with an automatic extractor biorobot m48 ( qiagen , hilden , germany ) by using the magattract virus mini m48 kit ( qiagen ) . cdna was obtained by using m - mulv reverse transcriptase ( promega , madison , wi , usa ) and random primers . aliquots of the dna and cdna were frozen at 40c until pcr for hbov detection was performed . respiratory samples were investigated for respiratory syncytial virus , influenza viruses a and b , parainfluenza virus types 14 , and adenovirus by cell culture and pcr . rhinovirus , coronavirus ( nl63 coronavirus included ) , and metapneumovirus were studied by pcr alone . yersinia enterocolitica , campylobacter spp . , and enteroinvasive escherichia coli o157 by standard culture methods . hbov detection was performed by pcr with primers derived from the np1 gene ( 1 ) . positive samples were retested and confirmed as positive by using a second pcr assay with primers derived from another location in the hbov genome ( vp1 gene ) ( 7 ) . amplified np1 and vp1 gene fragments ( 354 bp and 403 bp , respectively ) were sequenced and analyzed by using the blast software ( www.ncbi.nlm.nih.gov/blast ) . each pcr run included a negative control ( water ) that was treated as the clinical sample throughout , and pcr was performed with the usual precautions to avoid contamination . of the 527 stool samples analyzed from december 2005 through march 2006 , hbov was detected in 48 ( 9.1% ) . from a second group of 520 children <3 years of age who came to the pediatric emergency unit of our hospital with an episode of acute respiratory infection during the same period , a similar frequency of hbov detection was obtained ( 40/520 , 7.7% ) when nasopharyngeal aspirates were tested . analysis of np1 and vp1 partial gene sequences obtained from all fecal and respiratory hbov - positive samples showed a similarity of > 95% with previously published hbov sequences . of 40 hbov - positive respiratory samples , 25 ( 62.5% ) showed coinfection with other viruses ( respiratory syncytial virus in 13 , rhinovirus in 3 , influenza a in 3 , coronavirus oc43 in 2 , adenovirus in 1 , influenza b in 1 , respiratory syncytial virus and coronavirus oc43 in 1 , and influenza a and rhinovirus in 1 ) . of the 48 hbov - positive fecal samples , 28 ( 58.3% ) showed coinfection with another intestinal pathogen ( salmonella enteritidis in 1 , campylobacter jejuni in 5 , rotavirus in 14 , norovirus in 7 , and c. jejuni and norovirus in 1 ) . in this study , simultaneous detection of hbov and the incidence of coinfection in respiratory illness was similar to that observed in studies that were not limited to specimens that had already tested negative for other microorganisms and in which a wide number of agents were investigated ( 4 ) . adenoviruses have been associated with infection of the colon and the gut and are a cause of severe gastroenteritis in nonindustrialized countries . in this study , coinfection of adenovirus and hbov was detected in 1 respiratory specimen but these viruses together were not detected in any fecal sample . hbov and parvovirus b19 are the only 2 species of the parvoviridae family that have been associated with disease in humans . to date , hbov has only been detected in samples from the respiratory tract and has been associated with both upper and lower respiratory tract disease in infants and young children . the results of our study show that hbov is also present in the gastrointestinal tract in children with gastroenteritis with or without symptoms of respiratory infection . the fecal excretion adds new concern about the transmission of hbov . to our knowledge , this report is the first to document hbov in human feces . the high frequency of hbov detection in the feces of children with gastroenteritis and the absence of any other intestinal pathogen suggest that this new virus species is an enteric , as well as a respiratory , pathogen . further investigations to confirm this preliminary hypothesis and gain greater knowledge of the association between hbov and enteric disease are required .

in spain , human bocavirus ( hbov ) was detected in 48 ( 9.1% ) of 527 children with gastroenteritis at similar frequency as for children with respiratory illness ( 40/520 , 7.7% ) . fecal excretion adds new concern about the transmission of hbov . to our knowledge , this report is the first to document hbov in human feces .

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mauriac syndrome is a rare syndrome associated with type 1 diabetes ( t1 dm ) in children . the incidence of this syndrome had decreased significantly with introduction of long - acting insulin and better control of blood sugar . recently , there has been re - emergence of this syndrome , especially with the use of premix insulin . a 15-year - old type 1 diabetic boy was referred to us for evaluation of short stature . he was diagnosed to have t1 dm , following an episode of diabetic ketoacidosis ( dka ) 8 years back , and was started on premix ( 30/70 ) insulin . examination showed that he was significantly short for his age , height 131 cms ( less than 3 percentile ) , weight 28 kg ( less than 3 percentile ) and body mass index of 16.31 . he had abdominal fat deposition [ figures 1 and 2 ] and liver was palpable clinically 5 cms below costal margin [ figure 3 ] with no splenomegaly or free - fluid . short stature , abdominal obesity short stature , abdominal obesity investigations showed haemoglobin of 13.5 gm / dl . ultrasound abdomen showed liver enlargement 15.5 cms with increased echotexture , with normal spleen and portal vein and no free - fluid . on evaluation for diabetic status , he had an hba1c of 10.3% , urine microalbumin 70 g / gm of creatinine , and fundus showing background diabetic retinopathy . he had a bone age of 10.2 years , ( tanner whitehouse 2 ) thyroid - stimulating hormone ( tsh ) of 2.4 miu / ml and t4 of 8.8 microgm / dl . his growth hormone ( gh ) stimulation test and overnight dexa methasone suppression test were normal ( after blood glucose control and testosterone priming ) . based on the clinical history and investigations , the final diagnosis of mauriac syndrome was made and the patient was advised tight control of sugars . he was switched over to basal bolus regime , with glargine in the night and three doses of short - acting insulin before meals . mauriac in 1930 , described growth failure and maturational delay with hepatomegaly and abdominal distension in children with t1 dm , who were treated with short - acting insulin . hepatomegaly was commonly observed in children in the earlier periods of diabetic treatment , when only short - acting insulin was available and aglycosuria was the objective of treatment . it was noticed that the hepatomegaly regressed when the children were given the newly introduced protamine zinc insulin , providing better sugar control . in the late 1930s joslin clinic reported a case series of 60 youngsters with hepatomegaly , growth failure , delayed sexual maturation , and severe uncontrollable diabetes . equal incidence is reported in males and females , with most of the cases occurring during adolescence . with better control of sugar , the incidence of this syndrome has reduced rapidly and in the current era this is a very rare syndrome . two different forms of mauriac syndrome have been described , based on the presence or absence of obesity . in first form , as classically described , treatment with regular insulin alone there is associated cushingoid obesity and documented - wide fluctuation between hyperglycemia and hypoglycemia , suggestive of a pattern of over - and under - insulinization , with secondary hyperadrenalism . periods of over - insulinization appear to be essential for the development of obesity , and for the induction of hyperadrenalism . recently , mauriac syndrome has been reported in patients who are not obese and are without a history of alternating hypoglycemia and ketoacidosis . this occurs in patients who have been given regular , under the dose insulin . inadequate glucose to the tissues , decreased insulin - like growth factor-1 and gh levels , hypercortisolism , resistant or defective hormone receptor action contribute to stunted growth and delay in puberty . the cause of hepatomegaly is thought to be due to the deposition of glycogen in the liver , and similar subcutaneous deposition gives rise to the round moon like facies . growth failure , delayed puberty and hepatomegaly in mauriac 's syndrome improves with glycemic control . aggressive glycemic control has been associated with worsening of retinopathy , which should be monitored . mauriac syndrome is a rare manifestation of poorly treated t1 dm . with aggressive glycemic control ,

mauriac syndrome is a rare syndrome associated with type 1 diabetes ( t1 dm ) in children presenting with growth retardation , hepatomegaly , and cushingoid features . recently , there has been re - emergence of this syndrome , especially with the use of premix insulin . a 15-year old type 1 diabetic boy , who was on premix insulin with erratic blood glucose , was referred to us for evaluation of short stature . he had significant short stature , hepatomegaly , and cushingoid features . his growth hormone ( gh ) stimulation was normal , and so was the overnight dexamethasone suppression test , based on which the diagnosis of mauriac syndrome was reported . he was made to switch over to basal bolus regime , and was advised to follow - up for 6 months . he had reduction in hepatomegaly and a height gain of 3 cms .

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ultrasound ( eus)-guided celiac plexus neurolysis ( cpn ) has been reported to be effective in inducing pain relief . however , a 75-year - old man suffering from opioid refractory pain ( recorded as 9 according to visual analog scale ( vas ) ) due to an advanced stage iv histologically - proven pancreatic adenocarcinoma with liver metastases and celiac trunk infiltration not suitable for surgery , was referred to our center . eus confirmed the nodular hypoechoic lesion of 40 38 33 mm in the pancreas [ figure 1 ] . as the tumor stage was beyond any possibility of surgical radical care and in order to relieve patient 's symptoms , after informed consent was obtained , eus - guided cpn combined to eus - guided tumor ablation was arranged . under sedation with propofol , eus was conducted with a pentax fg-36ua ultrasound endoscope ( pentax europe ltd , hamburg , germany ) using a curved - array transducer . a 22 g needle ( cook medical inc , bloomington , indiana , usa ) was introduced though the endoscope 's working channel to inject 10 ml 2.0% lidocaine and 20 ml of ethylic alcohol 95% into the base of the celiac trunk at its origin from the aorta [ central approach , figure 2 ] . after performing cpn , 40 ml 75% of lesion volume of ethanol ( concentration 95% ) were directly injected into the tumor [ figure 3 ] . tumoral nodule in the body of the pancreas celiac plexus neurolysis performed via the central approach ethanol ablation of the pancreatic tumor no major complications were recorded during the procedure . in the days following the procedure , mild ( grade 2 ) diarrhea and fever were the only minor complications experienced by the patient . complete tumor devascularization was assessed by means of computed tomography ( ct ) 48 h after the procedure [ figure 4 ] . ca 19 - 9 dropped down to 56.84 u / ml at 2 weeks after eus . tumor response assessed by means of computed tomography ( ct ) 48 h after the procedure complete pain relief , namely vas 0 , was achieved 3 days after the endoscopic ablation . the patient remained pain - free without need of opioid , and was treated only with paracetamol for 20 weeks and afterwards experienced pain relief , ( defined as pain within 30% of baseline ) until death occurred 30 weeks after the procedure . advanced pancreatic cancer commonly induces severe refractory pain . in such patients , where opioids result often ineffective , eus - guided cpn has been reported to induce pain relief in 70 - 80% of cases . however , most patients achieve only suboptimal and transient relief , probably due to technical failure or further nociceptive impulses which can not be interrupted by the neurolysis . furthermore , definitive data on its efficacy in improving survival is still lacking . therefore , it was decided to try a combined approach directed both to the celiac plexus and the neoplastic mass , in order to delay tumor progression and lengthen pain - free survival as well as overall survival . the results were optimal in terms of pain relief and immediate tumor response ( assessed by means of ct and tumor marker levels ) . the present case demonstrates that the combined approach ( eus - guided ethanol ablation and cpn ) may be a valuable option aimed at improving both prognosis and pain control in patients with pancreatic cancer . randomized - controlled trials comparing eus - cpn alone to cpn associated to tumor ablation are needed to confirm this result .

a 75-year - old man suffering from opioid - refractory due to an advanced pancreatic adenocarcinoma was treated with endoscopic ultrasound ( eus)-guided celiac plexus neurolysis ( cpn ) combined to eus - guided tumor ablation . no major complications were recorded during the procedure . in the days following the procedure , mild diarrhea and fever were the only minor complications experienced by the patient . complete tumor devascularization was assessed by means of computed tomography ( ct ) 48 h after the procedure . the patient remained pain - free without need of opioid , and was treated only with paracetamol for 20 weeks . our results were optimal in terms of pain relief and immediate tumor response ( assessed by means of ct and tumor marker levels ) . the present case demonstrates that the combined approach ( eus - guided ethanol ablation and cpn ) may be a valuable option in patients with pancreatic cancer . randomized - controlled trials are needed to confirm this result .

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most of the children with cerebral venous thrombosis have an underlying chronic disease and those who are previously well have an acute infectious illness . obstructive hydrocephalus as a complication of cerebral venous thrombosis is rare and few cases are described . a previously healthy 4-year - old boy presented with 5 days of headache and vomiting . magnetic resonance imaging of the patient revealed obstructive hydrocephalus and magnetic resonance venography revealed thrombosis of the right transverse sinus [ figure 1 ] . low molecular weight heparin was started at a dosage of 1 mg / kg twice a day . control magnetic resonance imaging and magnetic resonance venography 1 month after the first event revealed partial resolution of hydrocephalus along with recanalization of the affected sinus [ figure 2 ] . hydrocephalus and absent flow in the right transverse sinus showing acute thrombosis improvement of hydrocephalus and recanalization of the affected sinus after a month of heparin therapy with folic acid and vitamin b6 and b12 replacement , the follow - up of the patient was given up by the family and he did not receive any treatment for 5 months . six months after the first event , the patient was again admitted to hospital with a similar clinical picture along with new thrombosis at the sagittal sinus . the patient is still followed up with low molecular weight heparin treatment after the second thrombosis attack . cerebral venous system thrombosis is an unusual event in childhood and clinical presentations , complications , diagnostic procedures , etiological investigations , and treatment modalities were not well established . clinical findings of cerebral venous system thrombosis include seizures , headache , vomiting , drowsiness , lethargy , and confusion . the patient may show acute or subacute picture related to progression of the disease . the present case presented with acute symptoms secondary to increased intracranial pressure . increased intracranial pressure is a well - known complication of cerebral venous thrombosis , but accompanying hydrocephalus is rarely described . the mechanism of hydrocephalus is considered to be secondary to an increase in venous pressure resulting in the blockade of cerebrospinal fluid flow into the sinuses by arachnoid villi . most of the patients with cerebral venous thrombosis have an increased intracranial pressure without an increase in ventricular size . why some patients develop hydrocephalus is not clearly understood and only a few adult cases were described . the etiologies regarding cerebral venous thrombosis are diverse and include head and neck infections and chronic disorders such as collagen tissue disorders , cardiac disease , and hematological abnormalities . half of the patients have prothrombotic states which include anticardiolipin antibodies , deficiencies of protein c and s , antithrombin iii and prothrombotic gene mutations such as prothrombin 20210 , factor v leiden , and mthfr mutations . the most frequent two common mthfr polymorphisms are c677 t ( alanin to valin transition ) and a1298c ( glutamine to alanine transition ) . evaluation of nine case control studies with total 382 patients having cerebral venous thrombosis revealed that carrying mthfr was not a risk factor for cerebral venous thrombosis . on the contrary a canadian study revealed that 29% of patients with cerebral venous thrombosis had mthfr polymorphisms . our case had a prothrombotic state with mthfr 1298 homozygous polymorphism without any risk factors . occurrence of clinical findings after cessation of heparin treatment suggests that mthfr polymorphism may be an important risk factor for cerebral venous thrombosis . anticoagulation is not recommended for asymptomatic and hemorrhagic cases . when used , low molecular weight heparin is the standard anticoagulant treatment in children . treatment may last for 36 months or it may be continued until recanalization if risk factors are eliminated . our patient responded well to low molecular weight heparin with recanalization of sinuses and recovery of hydrocephalus in both the attacks . in conclusion mthfr 1298 polymorphism may be an important risk factor and low molecular weight heparin should be the choice of treatment in cases without hemorrhage .

cerebral venous thrombosis is a rare form of stroke in childhood . increased intracranial pressure is a well - defined complication of cerebral venous thrombosis but obstructive hydrocephalus as a presentation finding of cerebral venous thrombosis is rarely described . a child case of cerebral sinus thrombosis presenting with obstructive hydrocephalus and management of clinical condition is presented with discussion of reported cases and treatment recommendations .

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a 70-year - old man was admitted to the emergency department with a 1-month history of coughing and dyspnea . he developed a productive cough with purulent sputum , left chest wall pain , and 3 days prior to arrival ecchymosis developed on the left upper quadrant of the abdomen . he did not have a recent history of thoracic or abdominal trauma , and it was unknown if he had a history of thoracic surgery . the initial chest x - ray showed a hyperdensity in the left lower lung , an obliterated diaphragmatic border with an atelectasis , and a decreased lung volume . the scan film showed a protrusion of the lung through the left 7th intercostal space ( fig . therefore , he was diagnosed with a lung herniation , and a medical conservative treatment was performed . on hospital day 10 , after experiencing uncontrolled coughing , the patient complained of aggravated dyspnea and left chest wall pain . the subsequent chest x - ray showed increased hyperdensity with a gas - filled area above the left dome of the diaphragm . he also showed dullness to percussion and chest wall tenderness . on hospital day 12 , a ct scan with contrast of the chest revealed herniation of the bowl and omental fat in the anterior portion of the left hemithorax ( fig . , the patient was transferred to the department of thoracic surgery and underwent an emergency operation due to the incarceration of the bowl and a parapneumonic effusion due to passive atelectasis . the operation revealed a partial agenesis of intercostal muscle , costal cartilage around the 7th anterolateral intercostal space due to the lack of developed intercostal muscle ( fig . 2a ) , an 8 cm defect of the diaphragm , and a herniation of the small bowel located in the anterior portion of the left thoracic cavity ( fig . the primary repair of the diaphragm was performed and the direct approximation of the 7th intercostal space was determined . a lung herniation is defined as a protrusion of the lung beyond the normal confines of the thoracic cavity through an abnormal opening in the chest wall . a condition associated with increased intra - thoracic pressure or that weakens the thoracic wall may cause a lung herniation . according to a report by goverde et al . , lung herniation is such a rare disease , that only about 300 patients have been reported with the disease in the world literature , and most were single case reports . congenital lung hernias are especially rare and consist of approximately 18% of all reported lung hernias . most congenital lung hernias are found in the supraclavicular area , whereas a lung herniation in the intercostal area is rare . a morgagni 's hernia is caused by a failure of fusion between the fibrotendinous portions of the sternal and the costal parts of the diaphragm . a morgagni 's hernia is also a rare disease . in a report by berman et al . , only 15 infants and children with morgagni 's hernia were admitted over a 20 year period at the hospital for sick children in toronto . the majority of patients present with a morgagni 's hernia in the neonatal period , but the hernia may remain undiscovered until later in life . morgagni 's hernia is secondary to an incomplete development of the diaphragm in contributing to the increase of abdominal pressure ; other contributing factors include trauma , severe exertion , and obesity . we located the agenesis of the intercostal muscle and the costal cartilage , and the congenital morgagni 's hernia was located near the intercostal herniation . the discoveries serve as evidence that this case involved a congenital disorder . in conclusion , we believe that the cause of the intercostal hernia combined with the morgagni 's hernia might have been due to incomplete development of the chest wall and diaphragm . the increased abdominal pressure due to recurrent cough is what aggravated the symptoms .

a 70-year - old male visited urgent care due to coughing for 1 month and left chest pain . he had no history of trauma . the initial chest computed tomography ( ct ) showed the 7th left intercostal lung herniation . a follow - up ct showed an intercostal lung herniation combined with a bowl herniation , which had developed due to a morgagni 's hernia . an emergency operation was performed due to the incarceration of the bowl and lung . the primary repair of the diaphragm was performed and the direct approximation of the 7th intercostal space was determined . we concluded that the defect of the diaphragm and the intercostal muscle was a congenital lesion , and the recurrent coughing was the aggravating factor of herniation .

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sox9 is a widely expressed transcription factor playing several relevant functions during development and essential for testes differentiation . it is considered to be the direct target gene of the protein encoded by sry and its overexpression in an xx murine gonad can lead to male development in the absence of sry . recently , a family was reported with a 178 kb duplication in the gene desert region ending about 500 kb upstream of sox9 in which 46,xy duplicated persons were completely normal and fertile whereas the 46,xx ones were males who came to clinical attention because of infertility . we report a family with two azoospermic brothers , both 46,xx , sry negative , having a 96 kb triplication 500 kb upstream of sox9 . both subjects have been analyzed trough oligonucleotide array - cgh and the triplication was confirmed and characterised through qpcr , defining the minimal region of amplification upstream of sox9 associated with 46,xx infertile males , sry negative . our results confirm that even in absence of sry , complete male differentiation may occur , possibly driven by overexpression of sox9 in the gonadal ridge , as a consequence of the amplification of a gene desert region . we hypothesize that this region contains gonadal specific long - range regulation elements whose alteration may impair the normal sex development . our data show that normal xx males , with alteration in copy number or , possibly , in the critical sequence upstream to sox9 are a new category of infertility inherited in a dominant way with expression limited to the xx background .

backgroundsox9 is a widely expressed transcription factor playing several relevant functions during development and essential for testes differentiation . it is considered to be the direct target gene of the protein encoded by sry and its overexpression in an xx murine gonad can lead to male development in the absence of sry . recently , a family was reported with a 178 kb duplication in the gene desert region ending about 500 kb upstream of sox9 in which 46,xy duplicated persons were completely normal and fertile whereas the 46,xx ones were males who came to clinical attention because of infertility.methods and resultswe report a family with two azoospermic brothers , both 46,xx , sry negative , having a 96 kb triplication 500 kb upstream of sox9 . both subjects have been analyzed trough oligonucleotide array - cgh and the triplication was confirmed and characterised through qpcr , defining the minimal region of amplification upstream of sox9 associated with 46,xx infertile males , sry negative.conclusionsour results confirm that even in absence of sry , complete male differentiation may occur , possibly driven by overexpression of sox9 in the gonadal ridge , as a consequence of the amplification of a gene desert region . we hypothesize that this region contains gonadal specific long - range regulation elements whose alteration may impair the normal sex development . our data show that normal xx males , with alteration in copy number or , possibly , in the critical sequence upstream to sox9 are a new category of infertility inherited in a dominant way with expression limited to the xx background .

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all procedures were approved by the animal care and use committee of boston children s hospital . we performed complete blood count and wright - geimsa analyses on peripheral blood recovered from adult pnt . genetic mapping and positional cloning were utilized to identify zgc : 162207 ( atpif1a ) as the candidate gene for the pnt locus on zebrafish chr . we employed qrt - pcr using taqman gene expression assays ( applied biosystems , carlsbad , ca ) to measure levels of atpif1a and atpif1b mrna . morpholinos ( gene tools , philomath , or ) against splice - site of atpif1a and atpif1b were designed and injected in wt embryos to verify loss - of - function phenotype . the crna for atpif1a , atpif1a - e26a , and atpif1b were injected in pnt embryos for complementation . the cdna prepared from wt and pnt embryos was sequenced , and the polymorphism in the 3utr of the atpif1a sequence was verified using sscp gels . the atpif1-silenced , differentiated hcd34 + and mel cells were stained with o - dianisidine to measure hemoglobinized cells , while mpfl cells were treated with drabkin s reagent to measure relative hemoglobin content . the loss of atpif1 protein and the state of mitochondrial structural proteins in mel cells were verified using western and electron microscopic analyses . we analyzed fluorescent intensities of tmre as a function of mitochondrial membrane potential , mg green as a function of atp levels , and ratio of carboxy snarf-1 to mitotracker green as a function of the mitochondrial matrix ph . we prepared fe - saturated transferrin , and measured fe incorporated in mitochondria and complexed in heme using a gamma counter . we examined ppix levels and the catalytic efficiency of fech in mel cells using spectrophotometric analysis . the mel cells were treated with fccp and 2,4-dnp , followed by analysis for hemoglobinized cells . human and yeast fech were treated with dtn , and subsequently their catalytic efficiency were measured . the crna for zebrafish fech or yeast fech was injected in pnt embryos , and their efficiency to rescue the anemia in pnt was measured using o - dianisidine staining and verified by using sscp analysis .

summarydefects in the availability of heme substrates or the catalytic activity of the terminal enzyme in heme biosynthesis , ferrochelatase ( fech ) , impair heme synthesis , and thus cause human congenital anemias1,2 . the inter - dependent functions of regulators of mitochondrial homeostasis and enzymes responsible for heme synthesis are largely unknown . to uncover this unmet need , we utilized zebrafish genetic screens and cloned mitochondrial atpase inhibitory factor 1 ( atpif1 ) from a zebrafish mutant with profound anemia , pinotage ( pnt tq209 ) . we now report a direct mechanism establishing that atpif1 regulates the catalytic efficiency of vertebrate fech to synthesize heme . the loss of atpif1 impairs hemoglobin synthesis in zebrafish , mouse , and human hematopoietic models as a consequence of diminished fech activity , and elevated mitochondrial ph . to understand the relationship among mitochondrial ph , redox potential , [ 2fe-2s ] clusters , and fech activity , we used ( 1 ) genetic complementation studies of fech constructs with or without [ 2fe-2s ] clusters in pnt , and ( 2 ) pharmacological agents modulating mitochondrial ph and redox potential . the presence of [ 2fe-2s ] cluster renders vertebrate fech vulnerable to atpif1-regulated mitochondrial ph and redox potential perturbations . therefore , atpif1 deficiency reduces the efficiency of vertebrate fech to synthesize heme , resulting in anemia . the novel mechanism of atpif1 as a regulator of heme synthesis advances the understanding of mitochondrial heme homeostasis and red blood cell development . a deficiency of atpif1 may contribute to important human diseases , such as congenital sideroblastic anemias and mitochondriopathies .

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opls - aa force field parameters and the tip3p model(22 ) are employed for potentials of alanine dipeptide and water , respectively . the first - order ermak and mccammon algorithm(1 ) is implemented in bd simulationswhere dt is a time step , di is the diffusion coefficient of atom i , and xi is a random noise vector obtained from a standard normal distribution . the diffusion coefficients of individual atoms are assigned according towhere i is the van der waals radius and is the solvent viscosity : the experimental values of for pure water and nabr solution are employed.(23 ) time steps of bd simulations are set to 10 fs , and trajectories of 300 ns are generated . we obtained the result of explicit - water md simulation by carrying out the nvt ensemble simulation including 491 water molecules . the time step of md simulation is set to 2 fs , and trajectories of 100 ns are generated . as was reported,(24 ) the ramachandran plot of alanine dipeptide strongly depends on the force field parameters .

we present an implicit solvent model based on the extended reference interaction site model ( xrism ) integral equation theory , which is a molecular theory of solvation . the solvation free energy is composed of additive potentials of mean force ( pmf ) of various functional groups . the xrism theory is applied to determine the pmf of each group in water and nabr electrolyte solutions . the method has been coupled to brownian dynamics ( bd ) and is illustrated here on alanine dipeptide . the results of the method are compared with those obtained by explicit water simulations and other popular implicit solvent models for detailed discussion . the comparison of our model with other methods indicates that the intramolecular correlation and the solvation structure influence the stability of the pii and r conformers . the results of nabr electrolyte solutions show that the concentration of electrolyte also has a substantial effect on the favored conformations .

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we conducted a preliminary screening of the 16s rrna methylase - producing bacilli on our gram - negative microbial stock of 2,877 strains isolated from japanese hospitals within the past several years . arbekacin , a semisynthetic aminoglycoside belonging to the kanamycin group , requires 2 modifications at the ( 6 ) aminogroup and the ( 2 ) hydroxyl group for inactivation , so this agent is not inactivated by known plasmid - mediated aminoglycoside - modifying enzymes . 512 mg / l ) was used as a marker for screening the 16s rrna methylase - producing strains . all arbekacin - resistant strains were subjected to polymerase chain reaction ( pcr ) analysis to detect rmta , rmtb , or arma , and all strains were pcr positive , except for a strain of acinetobacter demonstrating a very high level of resistance to arbekacin ( mic 1,024 mg / l ) . this strain was later shown to produce both aminoglycoside 6-acetyltransferase and 2-adenyltransferase ( 12 ) , so arbekacin was inactivated in this strain by both 6-acetylation and 2-adenylation . each pcr primer set was used to detect rmta and rmtb genes as in our previous reports ( 6,7 ) . the pcr primers for amplification of arma were newly designed ( forward : 5-agg ttg ttt cca ttt ctg ag-3 , reverse : 5-tct ctt cca ttc cct tct cc-3 ) , and the predicted size of the amplicon was 590 bp . these 3 sets of pcr primers were very reliable in detecting rmta , rmtb , and arma genes , respectively . each pcr amplicon was then subjected to sequencing analyses on both strands to confirm its nucleotide sequences for detecting mutations in the methylase genes . as reported in our previous study , rmta and rmtb genes had been found in p. aeruginosa isolates ( 6,10 ) and in 1 strain of s. marcescens ( 7 ) , respectively . as shown in the table , 5 p. aeruginosa strains isolated after our previous report ( 6 ) were rmta positive . the rmtb gene was additionally identified in 4 k. pneumoniae , 2 e. coli , and 1 k. oxytoca strains in japan . to our surprise , the arma gene , which had been found in various gram - negative microbial species belonging to the family enterobacteriaceae exclusively in europe as reported by galimand et al . ( 13 ) , was also identified in japan in 1 strain each of e. coli , s. marcescens , and acinetobacter sp . notably , the arma and rmtb genes were also recently identified in k. pneumoniae and e. coli in taiwan ( 9 ) . furthermore , the genetic environment of the arma gene found in c. freundii isolated in poland was similar to that of k. pneumoniae isolated in france . the genetic environments of the arma gene found in the 3 japanese microbial species , e. coli , s. marcescens , and acinetobacter sp . , ( genbank accession nos . ab116388 and ab117519 ) , were also similar to those found in europe ( genbank accession nos . af550415 and ay220558 ) . these findings suggest that the arma - producing gram - negative nosocomial microbes that harbor a very similar genetic environment carrying the arma gene have spread globally . as described previously , arbekacin still shows a very broad antimicrobial spectrum from gram - positive to gram - negative nosocomial microbes and has been approved solely to treat methicillin - resistant staphylococcus aureus ( mrsa ) infections in japan since 1990 to ensure the prudent use of this agent . the emergence and presence of the 16s rrna methylase - producing gram - negative bacilli , however , has not been well recognized in japan to date ; arbekacin has not been listed among the antimicrobial agents for daily antimicrobial susceptibility testing of gram - negative microbes . the use of semisynthetic aminoglycosides , including arbekacin , in japanese clinical settings for > 10 years may have promoted the emergence and dissemination of the 16s rrna methylase - producing gram - negative microbes in japan . the large amount of various aminoglycosides used in livestock - farming environments could have also been a selective pressure for the emergence and spread of pathogenic microbes that harbor genetic determinants for the newly identified 16s rrna methylases , as exemplified by recent isolation of arma - producing e. coli from swine in spain ( genbank accession no . since acquisition of multidrug resistance against clinically important antimicrobial agents such as carbapenems and fluoroquinolones has been developing rapidly worldwide , the acceleration of even greater aminoglycoside resistance among gram - negative bacilli promises to become an actual clinical concern in the near future , just as vancomycin - resistant enterococci ( vre ) did in the 1990s ( 14 ) . the emergence of gram - positive cocci including mrsa and vre that acquire the 16s rrna methylase could also be a grave clinical matter , although fortunately no such hazardous microbes have been identified . thus , steps must be taken to further block proliferation of these multidrug - resistant gram - negative super microbes , including p. aeruginosa , k. pneumoniae , and acinetobacter spp . , as well as multidrug - resistant cocci such as mrsa and vre , which have acquired an extraordinarily high level of resistance to various aminoglycosides through production of 16s rrna methylases , especially in clinical environments .

emergence of the newly identified 16s rrna methylases rmta , rmtb , and arma in pathogenic gram - negative bacilli has been a growing concern . arma , which had been identified exclusively in europe , was also found in several gram - negative pathogenic bacilli isolated in japan , suggesting global dissemination of hazardous multiple aminoglycoside resistance genes .

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the online version of this article ( doi:10.1007/s13300 - 014 - 0066-y ) contains supplementary material , which is available to authorized users . supplementary material 1 ( pdf 190 kb ) supplementary material 1 ( pdf 190 kb ) andrea messori , valeria fadda , dario maratea , sabrina trippoli and claudio marinai declare no conflict of interest . the analysis in this article is based on previously conducted studies , and does not involve any new studies of human or animal subjects performed by any of the authors . this article is distributed under the terms of the creative commons attribution noncommercial license which permits any noncommercial use , distribution , and reproduction in any medium , provided the original author(s ) and the source are credited .

backgroundin studying the therapeutic evidence of innovative drug treatments , increasing attention is being devoted to differentiating between results that indicate no significant differences among the treatments under examination ( no proof of difference ) and results that demonstrate the therapeutic equivalence among the treatments ( proof of no difference).aimour analysis was aimed at evaluating the degree of therapeutic equivalence for dipeptidylpeptidase-4 ( dpp-4 ) inhibitors given in type 2 diabetes as monotherapy or in combination with metformin.methodsequivalence was determined by developing a standard forest plot that incorporated the information on margins previously reported in randomized trials on these agents . the end point was hba1c change from baseline ; the equivalence margin was set at 0.25% change in hba1c . the clinical material was obtained from a systematic review on this topic.resultsgiven as monotherapy , linagliptin , sitagliptin , and vildagliptin ( but not saxagliptin ) met the equivalence criterion when compared with one another . given in combination with metformin , linagliptin , saxagliptin , sitagliptin , and vildagliptin showed an equivalent effect whereas alogliptin did not satisfy the equivalence criterion.conclusionsconsidering the most recent therapeutic guidelines , our results are of interest particularly as regards the information on dpp-4 inhibitors in combination with metformin . four of the five dpp-4 inhibitors under examination clearly showed to have the same effectiveness ; the fifth agent alogliptin failed to meet the equivalence criterion , but only because its superiority could not be excluded.electronic supplementary materialthe online version of this article ( doi:10.1007/s13300 - 014 - 0066-y ) contains supplementary material , which is available to authorized users .

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neonatal intestinal perforation ( nip ) is an extremely rare complication of intestinal hemangioma ( ih ) . neonates younger than 30 days and having perforation include more common etiologies such as necrotizing enterocolitis , meconium ileus , and spontaneous idiopathic as well as gastric perforation.1 nip has been associated with mortality rates of 40% to 70%.2 this report presents a rare case of nip resulting from ih . a 27-day - old male neonate was admitted with low - grade fever , abdominal distension , and bilious vomiting associated with bouts of diarrhea of 2 days duration . baby was a product of full - term spontaneous vaginal delivery with normal prenatal follow - up . before coming to our hospital , the patient weighed 4.1 kg and was febrile , irritable , and moderately dehydrated . plain abdominal radiographs suggested bowel obstruction versus ileus , therefore a barium meal follow through was obtained , which showed persistently dilated jejunal and proximal ileal loops but normal flow of contrast . computed tomographic scan with intravenous contrast was not done because of family history of allergic reaction to the dye . on the basis of the diagnosis of intestinal obstruction , a decision for exploratory laparotomy was made . laparotomy revealed dense inflammatory adhesions surrounding a solitary hemangioma located at the antimesenteric border 30 cm from the ileocaecal valve and on close inspection a small perforation was seen on one side of the hemangioma , which was sealed by extensive adhesions ( fig . other areas of the bowels inspected were normal and resection with primary anastomosis was done . dilated capillary spaces lined by single layer of endothelium with proliferation of endothelial cells in between . hemangiomas of the gastrointestinal tract are rare and account for only 0.05% of all intestinal neoplasms.3 they are commonly found within the small bowel , jejunum being the commonest site and compose 7 to 10% of all benign tumors.3 4 they have a tendency toward multiplicity , with solitary tumors being extremely rare.3 5 microscopically , ih may be classified as cavernous , capillary , or mixed types , commonest being the cavernous.6 the usual presentation is intestinal bleeding usually insidious presenting as anemia7 or sometimes acute and potentially life threatening.4 other forms of rare presentation include intussusception , obstruction , and perforation.8 9 10 ileal perforation is a rare complication of ih in neonates , and so far , only one case has been reported in the literature , by mcgaughey et al,11 who discovered evidence of ileal perforation due to ih while operating on a neonate with intestinal obstruction . ours is the second reported case of nip due to ih , and what makes it unique is the fact that the hemangioma belonged to the rare capillary type whereas the previously reported case was of the commoner cavernous type . diagnosis in both reported cases , including ours , were made only at surgery for presumed acute intestinal obstruction . although various causes of nip including the rare ih have been reported , diagnosis can be difficult and exploratory laparotomy has often proved to be the final diagnostic tool . although a rare cause of intestinal perforation in neonates , ih should be considered in the differential diagnosis .

intestinal perforation is an extremely rare complication of hemangioma of the small intestine in the neonatal period . this is a case report of a 27-days - old male infant who presented with signs and symptoms of acute intestinal obstruction . exploratory laparotomy findings revealed intestinal perforation due to solitary hemangioma in the ileum , which led to obstruction from peritoneal reaction and adhesions . there are two reported cases in the literature presenting with ileal perforation in the pediatric age group , but only one previous report mentioned in the neonatal period . because there are other more common causes of perforation in the neonatal period , intestinal hemangioma in spite of its rarity should be included in the differential diagnosis .

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fixed drug eruption ( fde ) is characterized by recurrent well - defined lesions in the same location each time the responsible drug is taken . we report here a rare case of fde induced by atenolol , a beta - adrenoreceptor - blocking agent . a 48-year - old tunisian woman was referred to our department for the appearance of five inflammatory plaques on both legs . she had been treated for hypertension with atenolol ( hypoten , al - hikma pharmaceuticals , jordan ) 100 mg once a day for six weeks . no other medications had been taken and she had not previously received beta - blocking agents . physical examination revealed five well - demarcated reddish and round plaques with an itching and burning sensation on both legs ( figure 1 ) . skin biopsy , taken from a lesion with no vesicular changes , showed focal necrosis of keratinocytes , hydropic degeneration of the basal cells , dermal edema and a perivascular lymphocytic infiltrate of the upper dermis . topical desonide ( locatop ) was applied twice a day and skin lesions resolved within two weeks with a residual pigmentation . 6 weeks after complete resolution , patch testing was carried out according to the international contact dermatitis research group ( jacobs et al 1999 ) recommendations with 10% atenolol in petrolatum on a previously affected site of the right leg ( figure 2 ) and on normal skin of the back . a positive reaction ( + + ) was seen at d2 and d3 on the left leg but no reaction was detected on the back . they mostly include nonsteroidal antiinflammatory drugs , nonopioid analgesics , sulphonamides , and tetracyclines ( savin 2001 ) . topical provocation testing has been reported to be useful and safe for the diagnosis of fde when applied on previously affected sites ( alanko et al 1987 ; alanko 1994 ; lee 1998 ; ozkaya - bayazit et al 1999 ) . different patch test methods ( open / occlusive ) and variations in their evaluation ( erythema of more than six hours duration / erythema and infiltration ) exist ( ozkaya 2008 ) . beta - blockers - induced fde are very rare ( palungwachira and palungwachira 1999 ; zaccaria et al 2006 ) . only two cases have been reported in the literature ( palungwachira and palungwachira 1999 ; zaccaria et al 2006 ) . they were induced by atenolol ( palungwachira and palungwachira 1999 ) and propranolol ( zaccaria et al 2006 ) . none of them was confirmed by patch testing or systemic provocation ( palungwachira and palungwachira 1999 ; zaccaria et al 2006 ) . thus , to the best of our knowledge , we report herein the first case of fde induced by atenolol and confirmed by a positive patch test on previously affected sites .

fixed drug eruption ( fde ) is characterized by recurrent well - defined lesions in the same location each time the responsible drug is taken . we report here a case of multiple fde induced by atenolol in a 48-year - old woman confirmed by positive patch test in previously affected sites . beta - blockers - induced fde are very rare . only two cases had been reported in the literature . to the best of our knowledge , this is the first case reported of atenolol - induced fde confirmed by a positive patch test .

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transcatheter closure of patent ductus arteriosus ( pda ) by use of the amplatzer duct occluder shows good results in properly selected patients.1 the advantages of the amplatzer duct occluder device include a user - friendly delivery system , the ability to retrieve or reposition the device when required , and a high complete closure rate ( > 99% complete occlusion of pda within 6 months of implant).2 although embolization of an amplatzer duct occluder is rare , it can occur . we present a case of retrieval of an embolized amplatzer duct occluder by use of a percutaneous method in a young man . transthoracic two - dimensional echocardiography and computed tomography ( ct ) confirmed pda ( fig . , we deployed the amplatzer duct occluder ii ( 9-pda2 - 05 - 06 , aga med . , usa ) after confirmation of the proper position by repeated angiogram . however , 5 min after successful deployment , the amplatzer duct occluder device was suddenly embolized into the branch of the right pulmonary artery ( rpa ) ( fig . 2a ) . before surgical removal , we decided to remove the embolized device by use of a percutaneous method after obtaining consent from the patient 's relatives . multiple attempts at removal by use of guidewire twisting , a goose - neck snare , and a radiofrequency ablation catheter were unsuccessful . because the embolized device was floating in the branch of the rpa , it moved into the distal portion of the rpa after several attempts of retrieval with the snare and ablation catheter . in order to stabilize the embolized device , a 5.020 mm balloon catheter was placed just distal to the embolized device and inflated . endomyocardial biopsy forceps ( cordis corp . , usa ) were introduced from the left femoral vein through an 8-fr sheath . after multiple attempts , we caught the screw attachment tip of the embolized device and removed it into the 8-fr shuttle sheath ( fig . subsequently , an amplatzer duct occluder 8 - 6 ( 9-pda-005 ) was carefully deployed via a venous route . the device was confirmed to be properly positioned across the defect by echocardiography and the ct angiogram ( fig . neither clinical complications nor a residual shunt was observed during the 6-month follow - up . transcatheter pda closure is currently the standard of therapy and is performed with high success rates and few complications.3 although the rate of device embolization is rare ( < 0.5% ) , this remains a major complication requiring urgent surgical management.4 the most common cause of embolization is the use of an undersized device . therefore , exact pda sizing and the use of the proper size of device is essential to avoid this potential complication . careful attention must be paid to imperfect alignment or malposition of the device or excessive tension on the delivery cable ; performing the wiggle procedure may reduce the acute failure rate of the procedure.5 excessive tension on the delivery cable was the main cause of embolization in our patient . in this case , stabilizing the floating device by balloon inflation played a pivotal role in success . the use of a larger 8-fr sheath during retrieval could make easier device entry into the sheath after capture of the embolized device . in general , the following techniques are recommended to increase the chances of successful retrieval : the use of a sheath 2 fr sizes larger than the delivery sheath , the use of stiff sheaths to avoid kinking , and cutting a bevel or notch at the end of the sheath to facilitate the entrance of the embolized device.6 our case illustrates a practical transcatheter removal technique for an embolized amplatzer duct occluder . even in procedures performed by the most experienced operators , thus , physicians have to keep in mind both the possibility and the treatment of this severe complication during pda closure .

transcatheter closure of patent ductus arteriosus with the amplatzer duct occluder shows excellent results . however , there is a risk of device embolization after deployment . we report the case of a 33-year - old man in whom an embolized amplatzer device was retrieved from the right pulmonary artery by a percutaneous method . we also review this uncommon severe complication and offer technical tips for percutaneous removal .

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bowel endometriosis occurs in approximately 10% of all patients with endometriosis and usually arises from the rectum and sigmoid colon at a rate of approximately 80% . conservative treatment with hormonal therapy is usually performed . however , if the patient hopes to become pregnant , an alternative to long - term hormonal therapy must be found . we report a case of lower rectal endometriosis performed using laparoscopically assisted low anterior resection of the lower rectum . a 34-year - old woman presented with pain during menstruation and was diagnosed with endometriosis of the lower rectum . despite treatment with an lh - rh agonist , she was unable to become pregnant and surgical removal of her endometriosis was recommended . on admission , tumor markers such as cea , ca-125 and ca-19 - 9 were 1.7 ng / ml , 31.9 u / ml and < 2.0 u / ml , respectively . on lower gastrointestinal series , poor extensibility of the lower rectum with irregular elevation and mucosal irregularity was observed . the portion of the rectum involved with endometriosis was approximately 35 mm from the anal verge ( fig . colonoscopic findings showed tumor - like submucosal tumor in the anterior wall of the lower rectum ( fig . 2 ) . abdominal computed tomography findings revealed a 2-cm mass without contrast enhancement in the lower rectum . concerning abdominal magnetic resonance imaging ( mri ) , a mass which was slightly enhanced and demonstrated mass effect on the surrounding organs was shown on gadolinium - enhanced t1-weighted images ( fig . there were adhesions to the right lower abdominal cavity , and a small amount of ascites was found in the pouch of douglas . exfoliation was started from the presacral region to the right side of the rectum and the rectococcygeus ligament was cut . exfoliation was continued to the levator ani muscle and mobilization of the left side of the rectum was performed . in front of the rectum , exfoliation was performed from the posterior wall of the vagina , but because the layer of exfoliation was unclear and tissue was solid around the tumor , the exfoliation was difficult . since the left hypogastric nerve was involved by inflammation surrounding the tumor , the nerve was cut , and subsequently the left lateral ligament was cut . after the inferior border of the tumor was confirmed by colonoscopy , the rectum was cut 1 cm distal to the inferior border of the tumor . then a 3-cm skin incision was made in the lower abdomen , the specimen was pulled up and the rectum was cut 5 cm distal to the superior border of the tumor . postoperatively , a rectovaginal fistula occurred on the 9th postoperative day , and an ileostomy was performed . after that , the patient 's postoperative course was uneventful and she left the hospital on the 25th postoperative day ; 4 months later the ileostomy was closed . endometriosis affects approximately 15 - 20% of women of child - bearing age , and bowel endometriosis occurs in 5% of all endometriosis cases . athmanathan et al . reported that 80% of the cases of bowel endometriosis arise from the rectum and sigmoid colon . symptoms of rectal endometriosis include dysmenorrhea in 57 - 85.3% of patients , dyspareunia in 55 - 57% , rectal pain in 41.2% , rectal bleeding in 14% , and tenesmus in 8.8% . in our case , the patient had rectal pain during menstruation . physical examination , computed tomography , mri and endorectal sonographic evaluation are useful in making the diagnosis . however , the sensitivity of mri for the diagnosis of colorectal endometriosis is much higher , at between 80 and 92.6% with a positive predictive value of approximately 89% . endorectal sonographic evaluation is noninvasive and its sensitivity and positive predictive value are both 100% . endorectal sonography was indicated in our case due to its high feasibility and lower cost compared to mri . significant resistance to the surgical treatment of colorectal endometriosis currently exists because of major complications such as colo- or rectovaginal fistulae . reported that rectovaginal fistulae occurred in 10.3% of patients . on the other hand , fleisch et al . reported the utility of surgical treatment for patients with persistent pain and found that 21 ( 91.3% ) of 23 patients reported improvement in their symptoms . for patients who desire to become pregnant , long - term hormonal therapy for endometriosis is contraindicated ; therefore , surgery is needed . bailey et al . reported that the pregnancy rate following surgery was 49% , strongly supporting the surgical treatment of rectal endometriosis . reported that all the items on the sf-36 health status and quality of life scores were significantly improved after laparoscopic colorectal resection for endometriosis . reported that the probability of requiring further surgery was 36% in patients with deep endometriosis , and furthermore , 38.6% of patients had residual or recurrent endometriosis . reported that the incidence of adhesion - related obstruction after laparoscopic colorectal surgery was 1.3% , which was lower than for open laparotomy ; therefore , laparoscopic surgery for colorectal endometriosis is recommend if further surgery is needed . for patients whose lesions are located on the lower part of the rectum , exfoliation is needed up to the levator ani muscle ; therefore , the laparoscopically assisted approach is more useful in providing a good operative field compared to open laparotomy . in our case , a rectovaginal fistula occurred on the 9th postoperative day and ileostomy was required , but intraabdominal adhesions were mild and ileostomy was performed easily using a laparoscopic approach . in conclusion , for patients with lower rectal endometriosis for whom hormonal therapy is contraindicated , laparoscopically assisted low anterior resection is recommended for its visual amplification effect , minimal invasiveness and palliation of symptoms .

a 34-year - old woman presented with pain during menstruation and was diagnosed with endometriosis of the lower rectum . despite treatment with an lh - rh agonist , she was unable to become pregnant and surgical removal of her endometriosis was recommended . preoperative magnetic resonance imaging revealed endometriosis localized between the neck of the uterus and rectum with indentation and scuffing . laparoscopically assisted low anterior resection was performed . exfoliation was started from the right side of the rectum to the presacral and retrorectal space , and the rectococcygeus ligament was transected . exfoliation of the retrorectal space was continued to the levator ani muscle and mobilization of the right side of the rectum was performed . in front of the rectum , exfoliation was started posterior to the wall of the vagina , but layers became unclear near the tumor as the tissue was solid in this region . the left hypogastric nerve close to the tumor was inflamed and it was cut . the layer of the exfoliation was connected to the right side of the rectum , the tumor was isolated from the vagina , and the lower rectum was transected at a point 1 cm distal to the tumor with a 60-mm linear stapler . reconstruction with a 31-mm circular stapler was performed using the double stapling technique . operative time was 520 min with a blood loss of 320 ml . on the 9th post operative day , a rectovaginal fistula occurred , and ileostomy was performed . the patient was discharged from the hospital on the 25th postoperative day , and 4 months later , stoma closure was performed .

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sodium valproate is a frequently used drug for the treatment of seizure disorders , bipolar disease and chronic pain . it is known to cause a serious complication , hyperammonemic encephalopathy which is characterized by acute onset of impaired consciousness , headache , vomiting , seizures , ataxia , generalized slowing on electroencephalography and rapid recovery after discontinuation . in this submission , we present a case of valproate - induced hyperammonemic encephalopathy where the major manifestation was restricted to bilateral cerebellar clinical features . a 19-year - old male presented with acute onset tremulousness , staggering gait and difficulty in walking and speech . he was a known case of idiopathic generalized epilepsy treated initially with carbamazepine ( 800 mg / day ) and recently switched over to sodium valproate ( 1000 mg / day ) before the onset of this acute complication . the patient showed bilateral cerebellar signs in the form of defective coordination in both upper and lower limbs with severe degree of gait ataxia and scanning speech . investigations including hemogram , liver function tests , renal function parameters , serum electrolytes and blood sugar showed normal results . thyroid function tests ( t3 , t4 , thyroid stimulating hormone ) and nutritional parameters including vitamin b12 levels were also found in normal range . however , serum ammonia level was raised to 106 mol / l ( normal range 12 - 47 mol / l ) . the levels of serum valproate and carbamazepine were found to be in the normal range ( serum valproate : 52 ug / ml [ range : 50 to 100 gm / ml ] and serum carbamazepine < 1.25 gm / ml [ range : 4 to 12 gm / ml ] ) . patient underwent magnetic resonance imaging of cranium , which turned out to be normal . with this background of clinical observations and laboratory assessment , a diagnosis of valproate - induced hyperammonemic encephalopathy the valproate was replaced by levetiracetam ( 500 mg ) two times a day along with carnitine supplementation . the patient showed rapid recovery and was able to walk without support after a week . his serum ammonia level normalized on repeat serum ammonia estimation ( 20 mol / l ) . valproic acid by virtue of its broad spectrum of action has application in various disorders like epilepsy , bipolar disorders , prophylaxis and treatment of migraine and neuropathic pain . although valproate - induced hepatic dysfunction leading to encephalopathy is a well - recognized entity , less commonly the drug can also produce an encephalopathy of non - hepatic origin by producing hyperammonemia , and is called as valproate - induced non - hepatic hyperammonemic encephalopathy ( vnhe ) . other causes of non - hepatic hyperammonemia include inborn errors of metabolism ( urea cycle enzyme defects , fatty acid oxidation defects ) , drugs like 5-fu , asparaginase , salicylate , halothane and enflurane , hematologic diseases like multiple myeloma and acute myeloblastic leukemia , hyperinsulinemia , hyperglycemia , distal renal tubular acidosis , parenteral nutrition and reye 's syndrome . the clinical presentation of hyperammonemic encephalopathy constitutes irritability , drowsiness , coma and occasionally these patients have paradoxical seizures . the presence of significant hyperammonemia with cerebellar signs and reversal of hyperammonemia , encephalopathy and disappearance of cerebellar signs and symptoms after discontinuation of sodium valproate confirmed the diagnosis of valproate - induced hyperammonemic cerebellar ataxia with metabolic encephalopathy . this view is also supported by generalized slowing in eeg suggestive of metabolic encephalopathy which also normalized after discontinuation of valproate . we estimated serum valproate and carbamazepine levels which were within normal limits although there is little correlation between valproate level and clinical effects because of the variable absorption rate and short half - life of the drug . in our study , there was decline in ammonia levels after withdrawal of valproate and subsequent disappearance of cerebellar symptoms and features of encephalopathy . there is scarcity of literature on unusual symptoms of valproate - induced hyperammonemic encephalopathy presenting as mainly cerebellar ataxia . cases have been reported where patients presented with acute onset of confusion , decline in cognitive abilities , and ataxia . we gave carnitine supplementation to our patient as valproate is known to enhance urinary excretion of l - carnitine , leading to depletion of its blood stores . thus we conclude that valproate - induced hyperammonemic encephalopathy can present mainly with cerebellar ataxia and a high index of suspicion is required for an early recognition , investigation , and treatment of this potentially life - threatening condition .

valproate - induced hyperammonemic encephalopathy is a rare event clinically characterized by impaired sensorium , vomiting , headache , seizures and focal neurological deficits . the pathogenesis of this dreadful complication is not well understood , although hyperammonemia has been implicated in causation of encephalopathy . in this submission , we have highlighted a case of valproate - induced encephalopathy who presented mainly with bilateral cerebellar features and generalized slowing on electroencephalogram . high index of suspicion of valproate - induced hyperammonemic encephalopathy is required if diffuse ataxia is present as it is a potentially reversible clinical disorder .

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aneurysmal bone cysts ( abcs ) are rare entities which cause expansile and destructive bone lesions characterized by reactive proliferation of connective tissue1,5 ) . they are benign lesions and can occur in any part of the skeleton and the spine can be affected up to 30% of the cases . abcs can cause symptoms such as back and/or dorsal pain , neurological deficitis , and pathological fractures . although abcs mostly occur in the distal part of femur and/or proximal part of the tibia , some cases have been reported in pelvis and posterior elements2,4,5 ) . abcs can occur rarely in the sacrum and this location has some difficulties in treatment because of the relations with the sacral nerves . togetherness of abc and fibrous dysplasia , giant cell tumors and/or osteoblastomas are defined as secondary abc by some authors and this association was seen aproximately in 20 - 30% of cases . diagnosis can be verified by ct scans and mri . in this paper , authors reported two rare cases with thoracic and sacral aneurysmal bone cysts . a 14-year - old male admitted to neurosurgery department with suffering of being unable to walk for 15 days . thoracic mri images and ct scans demonstrated a mass which causes mass effect on spinal cord ( fig . 2 day he was mobilised and his neurological examination was enough for walking with arm holder on postoperative 7 day . on the 5 months control of the patient there were no suffering and no instable images on x - ray and mr images ( fig . an 8-year - old male pateint admitted to us with right hip and back pain . in his history , he had fallen down from 2 meters . spinal mri revealed abc on the right side of the 3 sacral vertebra with an enlargement of 2419mm(fig . the second case is under control and no surgical treatment is suggested because of the patient 's age and observing no neurological deficits at the patient . a 14-year - old male admitted to neurosurgery department with suffering of being unable to walk for 15 days . thoracic mri images and ct scans demonstrated a mass which causes mass effect on spinal cord ( fig . 2 day he was mobilised and his neurological examination was enough for walking with arm holder on postoperative 7 day . on the 5 months control of the patient there were no suffering and no instable images on x - ray and mr images ( fig . an 8-year - old male pateint admitted to us with right hip and back pain . in his history , he had fallen down from 2 meters . spinal mri revealed abc on the right side of the 3 sacral vertebra with an enlargement of 2419mm(fig . the second case is under control and no surgical treatment is suggested because of the patient 's age and observing no neurological deficits at the patient . known as a non - neoplastic expansile bone lesion , abc has a consistance of blood - filled spaces separated by connective tissue septa containing bone and osteoclastic giant cells . discussions about thoracic and sacral aneurysmal bone cysts are limited and only a few cases have been reported3,7 ) . papagelapoulos et al described 44 pelvis abcs and 12 of them were in the sacrum6 ) . it is well known that total extirpation of sabc is so difficult and surgical results in treatment of sabc are excellent . these clinical findings include leg weakness and numbness , bowl or bladder dysfunctions . in our cases up to 60 - 70% of abc cases that occured in spine present with neurological deficits . the clinical aspects are pain due to the destruction and neurological deficits due to the fractures and compression . in our case the diagnostic problems are because of the expeditious growth of abc and its expansive destruction of bone . the diagnosis becomes more complicated if there is an extra - osseous and soft - tissue tumour mass . it also helps to evaluate the fluidfluid level , which is characteristic for abc on mr images1 ) . our first case was evaluated as a pathological fracture , and the patient underwent urgent surgery because of the compression on spinal cannal . but the second case was so typical for abc on the radiological examinations as if in the literature . the primary option for treatment is surgery . enneking classified 3 surgical types : 1-intralesional ( curettage and bone grafting ) , 2-marginal ( en bloc ) resection , 3-wide resection ( segmental resection)3,4,5,6,7 ) . the most important factors in preoperative planning are the location and the growing pattern of the abc . if abc is growing superficially and besides if it is not involving the one - third of the bone , in this case it will be more advantageous . this is really a good intervention for abc and local recurrences occur less com- monly . besides this , if the abc is so large and located in pelvis or spine extraperitoneal excision and bone grafting could be more difficult and risky . in similar cases like this , curettage and bone grafting remain a choiceable surgical technique . low - dose radiotheraphy can be performed after curettage and bone grafting as an other option for treatment5 ) . age , location , size and number of mitotic figures have been suggested for recurrence treatment of abc is difficult and histological examination should be done to prevent overlooked of an underlying more aggressive neoplasm .

aneurysmal bone cysts are rare entities which causes expansile and destructive bone lesions characterized by reactive proliferation of connective tissue . they usually grow rapidly with hypervascularity . in clinical practice they can be easily misdiagnosed due to the rare occurance and having no such typical findings as radiologically . most cases have uncommon pain symptoms , but rarely , if fractures occur , neurological findings can be seen and the surgical treatment , if needed , could be difficult . we will discuss our evaluations to two cases that we experienced in our clinic in this report .

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this whole genome shotgun project has been deposited at ddbj / embl / genbank under the accession jpul02000000 ( http://www.ncbi.nlm.nih.gov/nuccore/jpul00000000.2 ) . the stramenopile blastocystis is a common anaerobic protist living in the digestive tract of several animal groups . its prevalence in human often exceeds 5% in industrialized countries and can reach 100% in developing countries . although the role of blastocystis as a human pathogen remains unclear , it has been associated with acute or chronic digestive disorders and some epidemiological surveys have suggested an association with irritable bowel syndrome ( ibs ) , . in patients with ibs , blastocystis seems to be associated with a decrease of the fecal microbiota protective bacteria , bifidobacterium sp . and faecalibacterium prausnitzii . the life cycle of the parasite is poorly documented . among the parasitic forms described in the literature , the vacuolar stage which is maintained in vitro in axenic culture , blastocystis exhibits an extensive genetic diversity and seventeen subtypes ( st1st17 ) have been identified based on the gene coding for the small - subunit ribosomal rna among which the first nine are found in humans . briefly , it consists of an 18.8 mbp nuclear genome with 6020 predicted genes and a circular genome of 29 kbp located within mitochondria - like organelles ( mlo ) . other mlo genomes with conserved gene synteny we report the sequencing of the blastocystis st4-wr1 genome from an isolate of a laboratory rodent and cultured axenically . genomic dna was isolated using a qiagen dneasy blood and tissue kit and sequencing was performed with the illumina hiseq 2000 system ( genoscreen , lille , france ) . a total of 43.855.085 of 100-bp high quality paired - end reads were generated and were de novo assembled using the idba - ud algorithm . the output was then scaffolded using sspace and gaps were filled by gapfiller software . in total , 1301 scaffolds from 494 bp to 133,271 bp were obtained , with a scaffold n50 of 29,931 bp . the draft genome sequence of blastocystis st4 has a deduced total length of 12.91 mbp and a g + c content of 39.7% . assembly also provided a circular dna molecule of 27,717 bp in size with a g + c content of 21.9% corresponding to the whole mlo genome sequence . the maker pipeline was set with the results of ab initio gene prediction algorithms augustus and snap , the 6020 protein - coding genes of blastocystis st7 , ests of both blastocystis st7 and st1 and 414 manually - designed genes of the st4-wr1 isolate . basic information about the assembled genome and predicted genes are shown in table 1 . gene functions were annotated by blast2go and blast analyses with ncbi ( http://www.ncbi.nlm.nih.gov/ ) . the preliminary annotation data revealed that blastocystis st4-wr1 nuclear genome harbors 5713 protein - coding genes . the presence of proteases was determined using blast against merops database , and secreted proteases were identified using signalp 3.0 and wolf psort . this comparative analysis revealed that the st4 genome contains less duplicated genes than st7 and that more than 30% of st4 genes have no ortholog in the st7 genome at an e value cutoff of 10 . this also led to the identification of new candidate genes , in particular some potential virulence factors , including 20 secreted proteases that may be involved in the physiopathology of this parasite . among these proteases , 7 seem to be specific to st4 as no ortholog has been found in the st7 genome . sequencing and annotation of additional st ( st1 , st2 , st3 and st8 ) genomes are under progress and should be helpful for a better understanding of the genetic diversity , pathogenesis , metabolic potential and genome evolution of this highly prevalent human parasite .

the intestinal protistan parasite blastocystis is characterized by an extensive genetic variability with 17 subtypes ( st1st17 ) described to date . only the whole genome of a human st7 isolate was previously sequenced . here we report the draft genome sequence of blastocystis st4-wr1 isolated from a laboratory rodent at singapore .

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a 64-year - old man visited our hospital with the chief complaint of microscopic hematuria for the past 2 months . abdominal computed tomography ( ct ) revealed a homogeneous solid tumor with slightly low attenuation in the left renal sinus ( fig . altogether , these abdominal ct findings were suggestive of invasive urothelial carcinoma arising in the left pelvis with involvement of renal sinus soft tissue . nephroureterectomy was performed , and the cut surface of the renal sinus revealed a grayish - white solid tumor of rubbery consistency . the tumor was primarily located in the renal pelvis , but extensions to the renal calyces and proximal ureter were suspicious . the pelvic tumor mass measured 42.5 cm and exhibited peripelvic infiltrative features ( fig . 2 ) . however , the mucosal surfaces of the renal pelvis , ureter and calyces were smooth , and there was no evidence of urothelial malignancy . additionally , the mucosal layers of the renal pelvis , calyces and ureter were intact without abnormal urothelial changes . microscopically , the tumor occupying the renal sinus contained widely scattered , hyperplastic lymphoid follicles , characteristic of a lymphoproliferative lesion . the follicles varied in size and showed polarized germinal centers ; moreover , interfollicular spaces were markedly infiltrated by mature plasma cells , highlighted by cd138 immunostaining ( fig . 3 ) . immunostaining for and immunoglobulin light chains indicated that the plasma cells were polyclonal in origin . immunostaining for human herpes virus 8 ( hhv-8 ) was performed , the results of which were negative . these histological and immunohistochemical findings were compatible with a diagnosis of castleman 's disease of the plasma cell type . three months after the operation , there was no evidence of disease recurrence on follow - up abdominal ct . the occurrence of castleman 's disease in the renal sinus is exceedingly rare.1 to the best of our knowledge , only a few cases have been reported.1,3 - 6 the clinicopathological characteristics of the reported cases , involving six males and one female , are summarized in table 1 . although castleman 's disease generally shows no gender preference,2 cases involving the renal sinus appeared to show a male predominance . the median age for castleman 's disease is in the fourth decade.2 however , the mean age of the cases involving the renal sinus was 65 years . the main presenting symptoms included abdominal pain , weight loss , anorexia , and microscopic hematuria . five cases were of the plasma cell type , one of the hyaline vascular type and one of mixed type . the patient in the present case , a 64-year - old male , presented with symptoms of microscopic hematuria , and his disease was histologically classified as plasma cell type and clinically as unicentric type . although the exact pathophysiology of castleman 's disease is unknown , recent reports suggest that hhv-8 infection may stimulate b lymphocytes to induce interleukin 6 ( il-6 ) production in the mantle zone ; il-6 overproduction has been shown to be associated with the systemic manifestations of castleman 's disease , especially in cases of multicentric disease.7 in our case , immunostaining for hhv-8 was performed , but the result was negative . preoperative diagnostic imaging methods are not useful in differentiating castleman 's disease arising in the renal sinus from other diseases because of a lack of tumor - specific imaging features . previously , nishie et al.1 described the ct and magnetic resonance imaging features of three cases of castleman 's disease involving the renal sinus . they reported that the renal sinus lesions formed in castleman 's disease can appear as homogeneous masses with mild enhancement , such as is often observed in malignant lymphomas . thus , it is difficult , on the basis of radiological findings , to differentiate castleman 's disease from malignant lymphomas infiltrating the renal sinus . other differential diagnoses may include invasive urothelial carcinoma , granulomatous diseases , sarcomas , and metastases . consequently , pathological evaluation is currently the only method of identifying castleman 's disease of the renal sinus . here we have described an extremely rare case of unicentric castleman 's disease of the plasma cell type arising in the renal sinus . although preoperative diagnosis of castleman 's disease is difficult and accurate diagnosis is only possible by histopathologic evaluation , it should be considered in the differential diagnosis of renal sinus tumors .

castleman 's disease is a rare benign lymphoproliferative disorder that frequently affects lymph nodes of the mediastinal thorax and the neck . it very rarely affects the renal sinus . we report a case of castleman 's disease arising in the renal sinus in a 64-year - old man . the patient visited the hospital with the chief complaint of hematuria . abdominal computed tomography revealed a homogeneous mass in the sinus of the left kidney , radiologically interpreted as a malignant urothelial tumor . subsequently , nephroureterectomy was performed , after which microscopic examination of the specimen revealed a diffuse lymphoproliferative lesion with reactive lymphoid follicles of various sizes and prominent plasma cell infiltration of interfollicular spaces , highlighted by immunohistochemical staining for cd138 . the lesion was diagnosed as castleman 's disease of the plasma cell type . although preoperative diagnosis of castleman 's disease is difficult and the incidence is exceedingly rare , it should be considered in the differential diagnosis of renal sinus tumors .

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leri - weill 's dyschondrosteosis ( lwd ) is anautosomal dominant condition with variable penetrance characterized by mesomelic short stature and with madelung deformity . it is due to deletion or mutation in short stature homeobox ( shox ) gene . here , there is deficient growth of a volar and ulnar aspect of distal radialphysis , triangulation of corpus with proximal and volar shift of the lunate . a 13-year - old girl referred to us with a history of deformity of bilateral forearm from the age of 5 to 6 years . there was no history of pain in the joint of hands , trauma to the wrist and no history of similar illness in the family . patient was moderately built and significantly short for her age [ figure 1 ] . with height of 130 cm ( less than 3 percentile ) . upper segment was 69 cm , lower segment was 61 cm , weight of 35 kg and body mass index of 20.71 kg / m . secondary sexual characteristic tanner - whitehouse staging - b4 ( breast ) , p4 ( pubic hair ) , a3 ( axillary hair ) her elder brother had normal height for age and no any hand deformities and so were her parents . investigation showed hemoglobin of 12.5 g / dl , liver function test and renal function test were normal ca= 9.0 mg / dl alkaline phosphates 260 iu and phosphorus = 3.5 mg / dl . x - ray bilateral wrist showed malformed medial radial epiphysis with dorsal and ulnar shift and with increased length of phalanges suggestive of madelung deformity [ figure 2 ] . her ultrasound abdomen showed no hepatomegaly or splenomegaly and had normal sized uterus and ovary x - ray spine and x - ray elbow were normal [ figure 3 ] . her luteinizing hormone = 1.1 miu / ml follicle stimulating hormone = 2.4 miu / ml and karyotype was normal as was urine mucopolysaccharide screening . x - ray bilateral wrist based on the history , clinical examination , and investigations findings , the final diagnosis of lwd as a cause of madelung deformity was made . it is the most common cause of mesomelic deformity and is inherited as an autosomal dominant trait with variable penetrance . it is often seen in girls and becomes apparent in late childhood or early adolescence . madelung deformity , beside is also found in turner 's syndrome , pseudohypoparathyroidism , mucopolysaccharidosis and achondroplasia of distal radial epiphysis . madelung deformity was first described by malgaigne in 1885 and later by madelung in 1878 as a spontaneous forward subluxation of the hand . madelung deformity is an ulnar and dorsal curvature of the distal radius due to deficient growth of the volar and ulnar aspect of distal radialphysis , increased inclination of the distal radial joint surface , triangulation of the corpus with proximal and volar migration of and a prominent dorsal subluxation of ulnar head . recently , two subtypes of madelung deformity have been described , one with short stature and mesomelia consistent with lwd and the other with severe involvement of the entire radius with limited range of motion of extremity , markedly bowed appearance of the forearm and conspicuous radiographic deformity of the forearm and distal radius . the pathogenesis of lwd is linked to deletion or mutation in shox gene , present in the pseudoautosomal region of the sex chromosomes - xp23 and yp11 . in early human embryos it is expressed in the developing limbs ( particular elbow , knee , distal radius / ulnar and wrist ) as well as first and second pharyngeal arches and plays an important role in bone growth as well as development . shox gene is also associated with short stature in turner 's syndrome and also some causes of growth retardation like lws and langers mesomelic dysplasia . management is usually conservative . persistent pain and or severe deformity call for orthopedic surgery involving radial osteotomy . in addition , ulnar shortening in skeletally immature patient or excision of distal ulnar head in skeletally mature patients are done . surgical prophylaxis by distal resection of the abnormal part of distal radial epiphysis and its replacement by autologous fat ( also known as physeolysis ) has recently been shown to restore growth and minimized deformity . growth hormone supplementation is found to increase final height in turner 's syndrome , lws but not in langers mesomelic dysplasia . hand deformity is corrected by orthopedic surgery and for shox gene related short stature food and drug administration has recently approved growth hormone therapy .

madelung deformity is a rare inherited disorder associated with endocrine disorders like turner 's syndrome , pseudohypoparathyroidism , but can be seen with short stature homeobox deficiency conditions such as leri - weill dyschondrosteosis ( lwd ) and langers mesomelic dysplasia . it has also been reported following trauma to the distal radius epiphysis neoplasia mucopolysaccharidosis ( mps ) and achondroplasia . madelung deformity is an abnormality of distal radial epiphysis where in progressive ulnar and volar tilt of the articular surface occurring in association with distal subluxation of ulna . a 13-year - old girl was referred to us for evaluation of bilateral deformity of wrist and short stature . there was ulnar deviation and dorsal tilt of bilateral hands without history of pain to the joint trauma and family history of similar illness . on x - ray , wrist showed malformed distal radial epiphysis with dorsal and ulnar shift and with increased length of phalanges suggestive of madelung deformity . x - ray spine was normal . ultrasound abdomen showed normal uterus and ovary and her follicle stimulating hormone . luteinizing hormone was normal and so was urine mps screening . based on the above points the diagnosis of lwd was made .

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pityriasis rubra pilaris ( prp ) includes a spectrum of rare chronic , idiopathic inflammatory disorders with papulosquamous eruptions of unknown cause . prp shows consistent clinical heterogeneity ; consequently , it is hard to predict the outcome of treatment . a 29-year - old female presented for evaluation of a skin condition previously diagnosed as psoriasis vulgaris . the lesions first appeared at age six years with no preceding trauma or infection and were characterized by palmoplantar keratoderma and demarcated , hyperkeratotic plaques on the elbows and knees . the patient had been on many systemic treatments over the last two years without response , including cyclosporine ( 3 mg / kg / day for 3 months ) , methotrexate ( 15 mg / weekly for 4 months ) , adalimumab ( two subcutaneous injection of 40 mg at day 0 , a subcutaneous injection of 40 mg at day 7 and every 14 days thereafter for 16 weeks ) , etanercept ( 50 mg weekly subcutaneous injections for 12 weeks ) , infliximab ( 5 mg / kg given as an intravenous infusion at weeks 0 , 2 , 8) . physical examination showed a diffuse , orange - pink palmoplantar keratoderma [ figure 1 ] . well - defined keratotic follicular papules also involved the dorsal aspects of the hands and feet , elbows and knees [ figures 2 and 3 ] . a skin biopsy revealed alternating parakeratosis and orthokeratosis , pronounced irregular acanthosis , focal hypergranulosis and mild focal spongiosis . based on clinical and histologic findings , the patient was diagnosed having prp , type iv ( circumscribed juvenile ) . after voluntary , informed consent , ustekinumab 45 mg subcutaneously at weeks 0 and 4 , and quarterly thereafter ( patient 's weight = 55 kg ) was then started , the same posology as in psoriasis . keratoderma of the hands with a sharp demarcation of the borders diffuse transgrediens palmoplantar keratoderma on the dorsum of hands follicular hyperkeratosis and erythema on the elbows alternating parakeratosis and orthokeratosis , irregular acanthosis , focal hypergranulosis and a perivascular lymphocytic infiltration in the papillary dermis ( h and e 10 ) pityriasis rubra pilaris occurs equally in male and female patients , with a bimodal age distribution , peaking during the first and then the sixth decade . griffiths proposed a classification for prp in five subtypes , based upon age , duration , and type of cutaneous involvement . type i , or classic prp , is the commonest type ( 50% of cases ) and occurs in adults . the patient is usually erythrodermic with diffuse thickening of the palms and soles and possibly ectropion . 80% of patients experience clinical resolution within 3 years . on the basis of griffith 's classification clinical manifestations occurred in her prepubertal age and relapsed at age 27 , after a long - lasting remission . type iv prp develops in prepubertal children presenting with sharply - demarcated areas of follicular hyperkeratosis and erythema on the elbows and knees . a waxy , orange - red , diffuse , palmoplantar keratoderma is also commonly observed . a standard therapeutic approach does not exist as cases are few and treatment is protracted . an increasing number of reports document the effectiveness of tumor necrosis factor- ( tnf- ) blockers in recalcitrant prp . further , some case reports have documented favorable response of prp to ustekinumab , a fully human monoclonal antibody which binds to interleukin-12 ( il-12 ) and il-23 with high specificity and affinity . an upregulation of tnf mrna in lesional compared with nonlesional skin in two patients with type i prp has been demonstrated . a recent retrospective revision investigating treatment options showed a marked clinical in more than 50% of patients with type , a systematic review of reports of prp responding positively to tnf- blockers does not recommend them due to possible reporting bias and spontaneous remissions . in the literature , the patients who achieved remission with tnf- blockers or ustekinumab were all consistent with classical type 1 prp . our patient who presented a type iv prp was unresponsive to the tnf - blockers adalimumab , etanercept and infliximab . our clinical experience suggests that in patients with type iv prp , tnf and il-12/il-23 blockade may not be useful targets . since we observed a primary lack of response to all available tnf - blockers , we suggest that yet unmapped signaling pathways may be involved in type iv prp . there seems to be inadequate response of circumscribed variants of prp to standard therapies that are effective in classical prp .

treatment of pityriasis rubra pilaris ( prp ) may be difficult since no standardized therapeutic approach has been established . recently , tumor necrosis factor- ( tnf- ) blockers have been demonstrated to be favorable in the management of recalcitrant prp . the authors report a case of a patient who presented a type iv prp or circumscribed , juvenile type . such a condition follows an unpredictable course , presenting with diffuse , palmoplantar keratoderma and sharply - demarcated areas of follicular hyperkeratosis on the elbows and knees . treatment with all available tnf- inhibitors and ustekinumab did not prove to be helpful . the authors suggest that circumscribed variants of prp could respond to therapy in ways different from classical prp .

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teratoma is a special type of mixed tumor that contains recognizable mature or immature cells or tissues representative of more than one germ cell layer and sometimes all three . teratomas can develop in almost any area of the body , but usually occur in median sites . the most common sites are the sacrococcyx , anterior mediastinum , testicle , ovary , or retroperitoneum . 1 day old male baby was referred for respiratory distress secondary to the presence of an oropharyngeal mass . there no other abnormalities found in the head and neck region . under general anesthesia the lesion was excised . on the gross pathological examination , the excisional material was a polypoid lesion of 3 2 1.5 cm in size whose surface was covered with skin ( fig . histologically , the mass consisted of a core of lobules of mature adipose tissue admixed with fascicles of striated skeletal muscle and covered by keratinized squamous epithelium containing many hair follicles associated with sebaceous and eccrine glands ( fig . these findings confirmed the diagnosis of nasopharyngeal mature teratoma also known as congenital hairy polyp . . teratomas generally occur in 1 of 4000 births , but only 10% are found in the head and neck . they most commonly arise from the midline or lateral nasopharyngeal wall and some reports have described a slight female predilection , but jiang et al . found malignant teratoma to be more common in men . the majority of neonates with nasopharyngeal teratomas can be successfully intubated either via the oral or nasal routes , whereas the remainder usually require tracheostomy . in 6% of all cases , teratomas are associated with malformations such as cleft palate , bifid tongue , and bifid uvula . most of the congenital nasopharyngeal lesions present as an emergency respiratory problem and require immediate surgery . benign ones consist of mature tissue components , while those with malignant potential contain immature tissues ; benign teratomas may undergo malignant change with age . histopathological examination showed the mass in our case to be composed of multiple mature tissues with no juvenile cells , which confirmed a benign tumor . the main therapy of teratoma is complete surgical excision , which depends on the site of the tumor . patients with teratomas are more likely to require intensive airway management prior to surgical excision of the lesion . written informed consent was obtained from the patient 's parent for publication of this case report and accompanying images . a copy of the written consent is available for the review of the editor - of - chief of this journal on request .

highlightswe report a newborn with soft palatal mass.we excised the mass.on the gross pathological examination , it was polypoid lesion covered with skin . histologically , it consisted of a core of lobules of mature adipose tissue admixed with fascicles of striated skeletal muscle and covered by keratinized squamous epithelium containing many hair follicles associated with sebaceous and eccrine glands.these findings confirmed mature teratoma .

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metastatic disease is rare and usually occurs within the first two years after initial diagnosis , and is extremely rare after that time period . however , metastases to forearm bones are very rare with only very few reports published till date . here we present a case of bilateral retinoblastoma with metastases to right forearm bones four years after the initial treatment . an 8-year - old boy treated four years back for bilateral retinoblastoma with enucleation of left eye along with adjuvant chemotherapy and radiotherapy presented with a right forearm swelling . an x - ray revealed a mass lesion in right forearm with destruction of lower one third of right ulna . bone scan was performed three hours after intravenous injection of 5 mci of 99tc mdp . whole body images showed increased tracer uptake in right forearm bones [ figure 1 ] . static images revealed increased tracer uptake in middle and lower one - third of right ulna consistent with x - ray findings . in addition , bone scan showed involvement of lower one - third of left radius . however , special stains excluded ewing 's sarcoma and other primitive neuroectodermal tumors ( pnets ) . involvement of radius picked up by bone scan had important implication in deciding the nature of disease as ewings tumor with multi - focal disease as second primary is very unlikely . tc99m - mdp bone scan ; ( a ) whole body anterior view ; ( b ) whole body posterior view showing increased tracer uptake in right forearm bones . static images of bilateral forearms ; ( c ) anterior ; ( d ) posterior revealing involvement of right ulna and radius osseous metastases from retinoblastoma are reported most commonly in the skull and long bones . the prognosis for most children diagnosed with retinoblastoma is good , with a 5-year survival of rate of more than 90% . complications include local recurrence , metastases , and the development of a second primary tumor . focal and diffuse involvement of the bones and bone marrow is known to occur , but metastases are usually seen within two years of initial diagnosis and later metastases are said to be extremely rare . these patients are also at risk of increased second primaries like osteosarcoma , leiomyosarcoma , spindle cell sarcoma , malignant fibrous histiocytoma , rhabdomyosarcoma , angiosarcoma , ewing sarcoma , and pnet . these typically develop after a latent period of 815 years.[68 ] involvement of multiple bones would point the diagnosis towards metastases rather than multifocal second primary . imaging modalities available for skeletal metastatic work up include x - ray , ct , mri and functional imaging modalities like bone scan . x - rays are in general less sensitive to pick up the metastases , whereas whole body mri is not widely available , so conventional wb bone scan is essential in the metastatic work up of these patients . in our case , x - ray picked up ulnar involvement but radius involvement was missed . however , bone scan revealed radius involvement suggesting a metastatic disease rather than second primary . later , histopathology revealed round blue cell tumour involving both radius and ulna and ihc was negative for cd99 excluding diagnosis of ewings sarcoma . skeletal scintigraphy remains an essential diagnostic procedure in evaluation of these patients and can have important implications in management .

osseous metastases from retinoblastoma , the most common ocular malignant neoplasm of childhood , are reported most commonly in the skull and long bones . however , metastases to forearm bones are very rare . here we present a case of bilateral retinoblastoma with metastases to right forearm bones four years after the initial treatment .

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toxoplasmosis occurs in advanced stages of human immunodeficiency virus ( hiv ) infection and is the most common opportunistic infection of the central nervous system in patients with the acquired immunodeficiency syndrome ( aids ) , especially in those patients with a cd4 + count < 200 cells / mm . the most common clinical presentation of cerebral toxoplasmosis in patients with hiv infection is headache , focal neurological deficits and seizures . we present two cases with stroke - like presentation of cerebral toxoplasmosis from our centre . a 30-year - old right - handed nigerian woman was admitted to the university of calabar teaching hospital , nigeria , with a 1-week history of inability to move the left upper and lower limbs of acute onset . there was a history of headache , but no seizures , vomiting or loss of consciousness . she was not known to be hypertensive or diabetic , and she does not drink alcohol nor does she smoke . the patient was diagnosed to be hiv positive about 2 years prior to this admission and commenced on antiretroviral drugs ( arv ) but defaulted on therapy for about 1 year prior to the current presentation . her latest cd4 + count was not known . on neurologic examination , she showed left upper motor neuron facial nerve palsy and increased tone and brisk reflexes in both left upper and lower limbs . power was grade 0/5 and grade 1/5 in the left upper and lower limbs , respectively , on the medical research council scale , with a positive babinski sign on the left . a brain ct scan revealed a rounded ring - enhancing hypodense lesion in the parafalcine region of the right parietal cortex ( fig . a complete blood count revealed low haemoglobin ( 8 g / dl ) , esr 80 mm in the first hour , and cd4 + count 18 cells / mm . iu / l and toxoplasma igg was 202.0 iu / l , both markedly raised . a diagnosis of stroke - like syndrome due to cerebral toxoplasmosis in the background of hiv infection was made and the patient was commenced on pyrimethamine ( 200 mg at start , then 50 mg daily ) , clindamycin ( 600 mg every 6 h ) , folic acid ( 10 mg daily ) , septrin ( 960 mg b.i.d . ) , amoxicillin / clavulanic acid ( 625 mg t.d.s . ) , and haematinics . two weeks after treatment , the patient resumed arv therapy with truvada and lopinavir / ritonavir . power gradually improved to 4/5 in both limbs , and she started ambulating and was discharged to follow - up as an outpatient . a 35-year - old female was referred to the university of calabar teaching hospital , nigeria , with a 2-day history of left - sided weakness affecting her leg and arm and focal seizures involving her left upper limb . she had a history of hiv infection , diagnosed 4 years prior to the current presentation and treated with arv drugs . her last cd4 + count ( 6 months before ) was 28 cells / mm . on neurologic examination , there was left hemiparesis ( grade 3:5 on the medical research council scale for both left upper and lower limbs ) with increased tone and brisk reflexes and upgoing plantar reflexes ( babinski sign ) . an urgent brain ct showed a rounded marginally enhancing hyperdense lesion with perilesional oedema in the right thalamus ( fig . there was obliteration of the posterior horn of the ipsilateral lateral ventricle by the aforementioned mass . a similar but ill - defined lesion with more extensive perilesional oedema blood tests showed haemoglobin 10 g / dl , esr 106 mm in the first hour , cd4 + count 24 cells / mm and toxoplasma igg antibody 300 iu / l . based on these findings , a diagnosis of cerebral toxoplasmosis presenting with a stroke - like syndrome , on the background of hiv treatment failure , was made . the patient was discharged home to continue follow - up at the medical outpatient department .

toxoplasmosis is the most common opportunistic infection of the central nervous system in patients with acquired immunodeficiency syndrome ( aids ) . clinical presentation of cerebral toxoplasmosis in these patients includes headache , focal neurological deficits and seizures . prompt diagnosis and appropriate therapy results in rapid clinical and radiological improvement as well as good outcome for patients . in this article , we report two cases with stroke - like presentation of cerebral toxoplasmosis in the setting of hiv infection .

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the schedule shown in table 1 is for persons aged 0 through 18 years without delayed vaccination . for children and adolescents whose vaccination has been delayed for more than one month , the schedule should be referred to the catch - up immunization schedule ( table 2 ) . the schedule comprises two parts ; for infants and children aged 0 to 6 years and for children and adolescents aged 7 to 18 years .

this guideline contains the recommended immunization schedule for children and adolescents in korea by the committee on infectious diseases of the korean pediatric society , updated in march 2013 . it also includes a catch - up immunization schedule for children and adolescents who are behind the recommended schedule . these schedules are a minor revision of the corresponding parts of immunization guideline , 7th edition , of the korean pediatric society , released in 2012 . tables of this paper are published with quotation approval of immunization schedule english version of committee on infectious diseases and committee on publication of the korean pediatric society .

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facioscapulohumeral muscular dystrophy ( fshd ) is a common inherited muscular dystrophy presented clinically with slowly progressive weakness and wasting of facial and limb muscles and rare bulbar muscle involvement . we present herein a known case of fshd presented with recent onset of severe bulbar symptoms and was found to have myasthenia gravis ( mg ) based on electrodiagnostic study , elevated level of acetylcholine receptor antibody and dramatic improvement with choline esterase inhibitor agents . clinical presentation , electrodiagnostic and pathologic findings of this patient are described . a 70-year - old man presented to our department with complaint of 15-day history of progressive difficulty in chewing and dysartheria . he had a 50-year history of slowly progressive asymmetrical weakness of proximal upper limb muscles . examinations revealed reduction in forces of bilateral orbicularis oculi muscles , weakness and wasting of bilateral triceps muscles especially on right side and bilateral winging of scapula more prominent on right side . the legs and pelvic girdle muscles had normal forces . edrophonium test was performed and dysartheria and chewing difficulty showed dramatic improvement but had no effect on limb weakness . muscle biopsy showed myopathic changes with invariability in muscle fiber size , intramuscular infiltration of chronic inflammatory cells , mostly lymphocytes , few hyaline fibers and prominent fat infiltration . our patient 's bulbar symptoms showed dramatic improvement following administration of choline - esterase inhibitor agents . a 70-year - old man presented to our department with complaint of 15-day history of progressive difficulty in chewing and dysartheria . he had a 50-year history of slowly progressive asymmetrical weakness of proximal upper limb muscles . examinations revealed reduction in forces of bilateral orbicularis oculi muscles , weakness and wasting of bilateral triceps muscles especially on right side and bilateral winging of scapula more prominent on right side . the legs and pelvic girdle muscles had normal forces . edrophonium test was performed and dysartheria and chewing difficulty showed dramatic improvement but had no effect on limb weakness . muscle biopsy showed myopathic changes with invariability in muscle fiber size , intramuscular infiltration of chronic inflammatory cells , mostly lymphocytes , few hyaline fibers and prominent fat infiltration . our patient 's bulbar symptoms showed dramatic improvement following administration of choline - esterase inhibitor agents . it presents clinically with slowly progressive weakness and wasting of facial and shoulder girdle muscles and sometimes involvement of lower extremities . the clinical severity is wide ranging from asymptomatic individuals to wheel - chair dependent patients . any unusual changes in course of disease or development of unusual symptoms should raise the possibility of concomitant disease . sansone et al . reported a 69-year - old known case of fshd who presented with sudden deterioration of limb weakness and development of bulbar symptoms and was found to have mg based on repetitive nerve stimulation , elevated level of acetylcholine receptor - binding antibody and dramatic improvement following immunomodulator administration . reported a 50-year - old man with a 35 year history of fshd who presented with acute progressive weakness of lower extremities three weeks prior to admission . the patient was found to have mg based on decrement response on repetitive nerve stimulation , elevated level of acetylcholine receptor - binding antibody and improvement after thymectomy and administration of corticosteroid . in another report , mcgonigal et al . presented a 56-year old newly diagnosed myasthenic patient who found to have 40-year history of progressive foot drop and although our case is a rare coexistence of fshd and mg , low prevalence of both diseases , may raise the possibility of the presence of other etiologies . theoretically , it is related to breaking of immune tolerance to achrs as a result of muscle fiber degeneration . patients with genetic myopathies may occasionally develop antibodies to achr . while these antibodies may not have pathogenic effects , their production is likely to be a consequence of sensitization to achr secondary to muscle fiber damage , rather than through an immune process in thymus . muscle histopathological examination in some cases of fshd shows inflammatory changes , disproportionate to muscle fiber necrosis but the presence of mononuclear infiltration does not affect disease progression and the patients do not benefit from prednisone treatment . to the best of our knowledge , there are limited reports of concomitant occurrence of mg and fshd in literatures . although the association of mg with fshd in our patient could be an incidental finding , it may raise the possibility of innate immune response , i.e. autoinflammation in development of achr antibodies in genetic myopathies or it may suggest immune mechanisms in pathogenesis of fshd . moreover , our experience may warrant concomitant neuromuscular disorder in patients with unusual symptoms of fshd .

facioscapulohumeral muscular dystrophy ( fshd ) is a common inherited muscular dystrophy presented clinically with slowly progressive weakness and wasting of facial and limb muscles and rare bulbar muscle involvement . we present herein a 70-year - old man who was a known case of fshd with complaint of 15-day history of progressive difficulty in chewing and dysarthria and was found to have myasthenia gravis . related literatures have been also reviewed .

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linear psoriasis is a rare form of psoriasis , characterized by a linear distribution of the psoriatic lesions along blaschko 's lines . the pathogenesis of linear psoriasis is not clear , but it could be explained by the well - established concept of genetic mosaicism . a 56-year - old previously healthy woman presented with a 3-month history of multiple confluent erythematous papules and plaques covered by scales . the papules and plaques had well - defined and sharply demarcated boundaries , ranged from 3 to 10 mm in diameter , were limited to the right side of her body and were arranged along blaschko 's lines with a marked mid - line cutoff . the lesions were first noticed in the right scapular region and progressively extended within a few weeks to the lateral aspect of the right superior limb , the right side of the trunk , the abdomen and the anterior aspect of the inferior limb , especially pronounced in the proximal third of the thigh and the knee ( fig . the patient denied any episodes of infection preceding the dermatosis . no psoriasis - form nail or scalp lesions were observed , and there was no personal or family history of psoriasis . the histopathologic analysis of a skin biopsy revealed orthokeratosis , parakeratosis and spongiosis - form munro 's microabscesses , in association with a regular elongation of rete ridges , suprapapillary thinning , and an absence of granular cell layers ( fig . a slight improvement was noticed after 1 month of combined treatment with betamethasone valerate and calcipotriol ointment . after complete laboratory exams including blood cell count , renal , hepatic and lipid panels , hbv and hcv serologies , and a chest radiograph , the patient was started on methotrexate 10 mg weekly with excellent response . in the 26th week of treatment , as only residual lesions persisted , the methotrexate dose was reduced to 7.5 mg weekly and maintained until the present time ( cumulative dose of 465 mg ) with no clinical relapse . there are few cases reported in the literature [ 1 , 2 , 3 ] , and therefore there is no estimated prevalence . also because of its clinical and histological similarity to ilven , the main differential diagnosis is ilven , and the distinction between the two entities has been discussed in the literature [ 4 , 5 , 6 ] . a late onset of asymptomatic to slightly itchy lesions with a possible involvement of scalp and nails and a favorable response to antipsoriatic treatment favors the diagnosis of linear psoriasis [ 8 , 9 ] . in contrast , ilven lesions usually occur in the first months of life , are slowly progressive , very pruritic and highly refractory to antipsoriatic therapy . as for the histological features , ilven classically demonstrates hypergranulosis and parakeratosis alternating with hypogranulosis and orthokeratosis . on the other hand , the classic features of psoriasis are hyperkeratosis , parakeratosis , the absence of granular cell layers , an elongation of rete ridges , suprapapillary thinning and munro 's microabscesses , which can also be seen in ilven . immunohistopathologic studies may be helpful in distinguishing the two conditions , as done by vissers et al . : in ilven patients , the number of ki-67-positive nuclei tended to be reduced , whereas the number of keratin-10-positive cells was increased compared with psoriasis patients . involucrin expression , another marker , is absent in ilven patients but detectable in psoriasis . the pathogenesis of linear psoriasis is not clear , but it could be explained by the well - established concept of genetic mosaicism .

a 56-year - old woman presented with a 3-month history of erythematous plaques covered by scales and limited to the right side of her body . the plaques were arranged along blaschko 's lines with a marked mid - line cutoff . the histopathologic analysis of a skin biopsy in conjunction with the anamnesis allowed the diagnosis of linear psoriasis . our patient showed a good clinical response to antipsoriatic treatment .

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malignant tumors which originated from mesenchymal tissue , has occurred very rarely in the breast . the metaplastic carcinomas which have characterized by a combination of mesenchymal and epithelial components would be uncommon malignancies of the breast . the chondrosarcoma has been a typical example of these rarest tumors of the mesenchymal tissue . a 65 years old man has presented in our department with a complaint of a right sided breast mass which has rapidly grown for 5 months . breast palpation has revealed a painless , less mobile , and firm to hard mass of 1010 cm with regular margins in area of right breast . contrast enhanced mri ( figures 1a and b ) of breasts has revealed huge mixed signal intensity multi lobulated cystic - solid extra - pulmonary mass lesion involving the right anterior chest wall extending from infra clavicular region to the level of xiphisternum measuring 10.4 cm ( si ) 10.3 cm ( ap ) 9.9 cm ( trans ) appearing predominantly hyper intense on t2w and hypo intense on t1w . heterogeneous predominantly peripheral solid tumoral enhancement has observed with multiple large loculated central areas of necrosis and intensely enhancing septae . histopathology has revealed the overall appearances of low - grade chondrosarcoma with a tumor composed of lobules of cartilage of varying size separated by fibrous tissue . immunohistochemical studies have performed by standard revealed that chondrosarcomatous elements were positive for s-100 and vimentin , but negative for cytokeratin and also for estrogen and progesterone receptors . this paper has discussed one of the rarest mesenchymal malignancies of the breast , primary chondrosarcoma . as a primary breast tumor , chondrosarcoma might occur in three different forms : as a pure neoplasm ( pure chondrosarcoma ) , as the stromal component of a histologically malignant phyllodes tumor , or as chondrosarcomatous differentiation in a metaplastic carcinoma . in this report prognosis of chondrosarcomatous breast tumors has not fully known , because many of the reported cases were difficult to analyze ( owing to lack of detailed clinical or morphologic information ) . these tumors were usually large - sized that have occurred in more than 40 year old woman . axillary lymph nodes have found in 14 - 29% of the cases , most of which were reactive hyperplasia . the present case substantiates the clinical findings of previously reported cases . to diagnose a primary chondrosarcoma of the breast , other types of pure sarcoma , such as spindle cell sarcoma , neuroectodermal tumor , angiosarcoma etc , have also been reported [ 6 , 7 ] . the history of the patient had an important feature as the mass had grown rapidly without systemic and deleterious effect on the patient s health status . these tumors have tended to grow rapidly and present themselves as a mass for a short duration [ 2 , 3 , 7 ] . a large multilobular mass with regular margins and without a sign of regional invasion has detected by palpation . previous reports have also pointed out that these large tumors have not generally invaded skin and regional lymph nodes despite their locally advanced nature [ 2 - 4 , 7 ] . a relatively circumscribed , well demarcated mass , as in our patient , was an imaging characteristic of a pure mesenchymal or a metaplastic carcinoma with sarcomatoid differentiation . it has been redported that imaging studies seldom led to the diagnosis of sarcoma in a suspected benign lesion . the mass was complex echoic on ultrasound and has shown round hyperdense opacity on mammography [ 4 , 7 , 8 ] . the very limited number of such cases has not permitted us to establish an appropriate therapeutic approach . chondrosarcoma in common locations has generally known as refractory to all types of conventional chemotherapy and radiotherapy . pure chondrosarcoma and metaplastic cancer of the breast has rarely invaded axillary lymph nodes and would be generally hormone receptor - negative [ 1 , 2 , 4 , 11 ] . this extremely rare tumor has tended to grow rapidly , and it was usually large at first physical examination . a large , hyper dense and complex echoic mass with regular margins has given the impression of a benign tumor on mammography and ultrasound . despite its large size , it has not invaded local and regional structures . regarding systemic management , there was no standard treatment protocol , and a large variety of chemotherapy protocols have been employed in treating this disease . systemic therapy principles have been derived from small retrospective case reviews of primary breast chondrosarcomas and extrapolated from studies of non - breast chondrosarcomas , since the clinical behavior and histology were similar . this fact has been supported the theory that adjuvant therapy with estrogen antagonists and other hormone manipulations had no role in treatment of mammary sarcomas . the adjuvant treatment could decrease the rates of local and systematic recurrences , but the results were not significant because of the rarity of this pathological entity and the small numbers of cases have reported , which made the evaluation of the role of the chemotherapy and the radiotherapy in the primary breast chondrosarcoma more difficult . it has seemed to be very important to identify the mammary primary sarcomas as entity separated from the carcinomas of the breast . the primitive chondrosarcoma has remained a rare pathology , among which the therapeutic modalities and the forecast were credibly identical to those of the sarcomas of the same type arising in the other localizations . it has seemed to be very important to identify the mammary primary sarcomas as entity separated from the carcinomas of the breast . the primitive chondrosarcoma has remained a rare pathology , among which the therapeutic modalities and the forecast were credibly identical to those of the sarcomas of the same type arising in the other localizations .

breast sarcomas have relatively been rare and accounted for 1% of all primary malignant tumors of the breast . pure and primary chondrosarcoma of the male breast would be an extremely rare tumor . it might arise either from the breast stroma itself , or from underlying bone or cartilage . a 65-year - old man has presented with a rapidly growing breast mass since 5 months . physical examination has established a large firm to hard mass with regular margins in the region of right breast . there was no axillary lymphadenopathy . contrast enhanced mri of breasts has shown a mixed - signal intensity multi lobulated cystic - solid mass ( 10.4 cm 10.3 cm 9.9 cm ) appearing predominantly hyper intense on t2w and hypo intense on t1w . the tumor has diagnosed as a low - grade chondrosarcoma of the breast by histopathological and immunohistochemistry analysis . right sided radical mastectomy with grafting has done . it has seemed to be very important to identify the mammary primary sarcomas as entity separated from the carcinomas of the breast .

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in clinical practice , one may encounter female patients with infertility which may be attributed to primary or secondary causes . in the group of primary infertility , congenital anomalies form relatively small but significant group . mayer - rokitansky - kuster - hauser syndrome ( mrkh ) is characterized by congenital absence of the uterus and vagina . there is a failure of development of the mullerian derivative of the vagina and the portions of the mullerian ducts that form the uterus . the american fertility society classification , based on uterine anomalies is most commonly used to classify mullerian duct anomalies . mrkh syndrome is a class 1 mullerian duct anomaly , and it has been subdivided into typical or type a and atypical or type b. patients with type a syndrome have symmetric muscular buds , normal fallopian tubes . patients with type b have asymmetric muscular buds , abnormal fallopian tubes , and may be associated with other congenital anomalies such as renal , skeletal , hearing , cardiac , and ocular anomalies . out of few genes which are identified in causation , one candidate is a mutation of the wnt4 gene , a developmental gene which regulates growth and differentiation during embryogenesis . women with this syndrome are characterized by the presence of 46 xx karyotype , normal female secondary sex characters , normal ovarian functions , and underdeveloped vagina . the presence of leiomyoma in mrkh syndrome is very rare , and only a few cases have been reported in the literature . here , we report a case of mrkh syndrome ( type a ) with multiple leiomyomas originating from the rudimentary uterus . twenty - five years married female presented to the gynecology outpatient department with primary amenorrhea . secondary sexual characters revealed the presence of pubic hair and axillary hair ( tanner stage 5 ) [ figure 1a ] . ultrasonography examination showed agenesis of the uterus with right adnexal mass measuring 5 cm 4 cm 4 cm . differential diagnosis of leiomyoma of the rudimentary uterus in mrkh syndrome includes ovarian fibroma , a gastrointestinal stromal tumor of the intestine and extravesical leiomyoma of the urinary bladder . values were : serum follicle stimulating hormone 7.17 miu / ml ; serum leutenizing hormone 15.6 miu / ml ; serum prolactin 10.64 ng / ml ; and cancer antigen 125 4.5 iu / ml . with a provisional diagnosis of mrkh syndrome associated with right adnexal mass , she was taken for laparotomy . a rudimentary bicornuate uterus measuring 1.5 cm 1.5 cm with a small cervix measuring 1 cm 1 a total abdominal hysterectomy was performed in view of the presence of multiple nodules in a nonfunctional uterus . multiple myomertial nodules [ figure 1b ] were seen arising from the rudimentary right and the left horns of the uterus [ figure 1c ] . on cut section of the specimen , uterine horns were found noncommunicating , and they had a rudimentary endometrial cavity . all the nodules were well circumscribed , grayish white and had a characteristic whorled appearance . histological examination revealed features of leiomyoma [ figure 1d ] with rudimentary mullerian lining [ figure 1e ] . failure of fusion and development of mullerian ducts results in muscular thickening at the proximal end of each tube that are joined in the midline by a visible and palpable cord resembling hypoplastic bicornuate uterus without an endometrial lining . rarely , an active endometrium can exist with uterine analog , which becomes active in the presence of well - estrogenized state . in literature , it is mentioned that fibroids and adenomyosis rarely develop in the rudimentary nonfunctioning uterus . cytogenetic abnormalities in the form of spontaneous chromosomal rearrangements are known to occur in uterine leiomyomas . these chromosomal arrangements may be responsible for the initiation and progressive growth of the leiomyomas . the leiomyomas are found to have higher concentration of estrogen receptors as compared to normal myometrium . these might explain the propensity to develop leiomyoma in the presence of exogenous and endogenous estrogen . as the proximal ends of mullerian ducts have smooth muscles , the presence of leiomyoma in a case of mullerian agenesis is a theoretical possibility . however , the occurrence of multiple leiomyomas in a rudimentary uterine bulb has been rarely reported earlier . the possible reason for this uncommon occurrence could be a decreased concentration or sensitivity of the estrogen receptors or a lesser genetic predisposition for the clonal chromosomal abnormalities that are observed in women with normal uterus with leiomyomas . in our patient , we could not perform cytogenetic and receptor studies to point out the exact etiopathogenesis of this unique occurrence of multiple leiomyomas in the rudimentary uterine bulbs . hysterectomy was performed in our case in view of nonfunctioning uterus and risk of recurrence after myomectomy . treatment for patients of mrkh syndrome with leiomyoma is myomectomy or hysterectomy and vaginal reconstruction ( vaginoplasty ) . frank 's dilatation method , williams vaginoplasty , vecchietti procedure , abbe - mcindoe vaginoplasty and davydov technique . with advances in minimal access surgery the ovarian function is normal in these patients so that ovum can be retrieved and with the help of a surrogate mother , it is possible to have fertility potential .

mayer - rokitansky - kuster - hauser ( mrkh ) syndrome is a rare disorder described as aplasia or hypoplasia of uterus and vagina due to an early arrest in development of mullerian ducts . women with this syndrome are characterized by the presence of 46 xx karyotype , normal female secondary sex characters , normal ovarian functions , and underdeveloped vagina . the presence of leiomyoma in mrkh syndrome is very rare , and only few cases have been reported in the literature . here , we report a case of mrkh syndrome with multiple leiomyomas originating from the rudimentary horn of uterus in 25 years married , phenotypically female patient .

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in the search for new agents to protect the lung from injury , kuklin and colleagues report that tezosentan , a non - selective endothelin-1 receptor antagonist , reduces pulmonary edema in endotoxemic sheep , in parallel with a prevention of protein kinase c- activation . acute lung injury ( ali ) and its more severe form , acute respiratory distress syndrome ( ards ) , are syndromes of acute respiratory failure secondary to permeability , non - cardiogenic , pulmonary edema . ali / ards is a major cause of morbidity , death and cost in intensive care units . alveolar edema accumulates in ali / ards mainly because the permeability of the capillary ( endothelium)alveolar ( epithelium ) barrier is increased . this mechanism allows edema formation at normal capillary pressures and greatly increases the rate of edema formation at elevated capillary pressures . in addition , pressure elevation in the pulmonary circulation and mechanical stresses applied to the lung ( during mechanical ventilation , for example ) may cause " stress failure " in lung capillaries and alveoli , as evident in the formation of breaks and discontinuities in the endothelial and epithelial membranes of the blood gas barrier . the american european consensus conference on ards defined ali / ards as a " syndrome of inflammation and increased permeability " . hence , it is now widely accepted that the pathophysiology of ali / ards is driven by an aggressive inflammatory reaction that damages the alveolocapillary unit . after rapid recruitment of leukocytes to the inflamed site , there is activation of mediator cascades including the production of cytokines , chemokines , acute phase proteins , free radicals , complement , coagulation pathway components and focal upregulation of adhesion molecule expression units . several cytokines , such as tumor necrosis factor alpha ( tnf- ) , interleukin ( il)-1 , il-6 and il-8 , have been found in bronchoalveolar lavage fluid and plasma of patients with ards . inflammatory mediators amplify endothelial injury directly or by recruiting inflammatory cells into the vascular , interstitial and alveolar spaces . in addition , some mediators may also alter endothelial permeability by disturbing intracellular signaling pathways . tnf- and -thrombin have been shown to activate protein kinase c - mediated mechanisms that participate in the pulmonary endothelial response to agents involved in lung injury . protein kinase c is a ubiquitously expressed family of kinases that have a key role in regulating multiple cellular activities . activation of specific protein kinase c isoforms , most probably protein kinase c- , may cause lung endothelial dysfunction through several mechanisms . endothelins are a family of 21-amino - acid isopeptides . initially described as strong vasoconstrictors , for example , transgenic mice overexpressing endothelin-1 release increased amounts of tnf- , interferon- , il-1 and il-6 . the endothelin system is activated in clinical lung injury and in various types of experimental lung injury , and several endothelin receptor antagonists have been reported to exert protective effects in some models of ali / ards . endothelins may thus play a pathophysiologic role in ali / ards and promote pulmonary edema by increasing the filtration pressure ( as postcapillary vasoconstrictors ) , and also by increasing capillary permeability ( as inflammatory mediators ) . the results of kuklin and colleagues are in accordance with this hypothesis and provide further insight into an intracellular effect of endothelin receptor antagonists ( i.e. prevention of protein kinase c- activation ) . endothelin receptor antagonists have been made available recently for clinical use in the treatment of pulmonary arterial hypertension . these drugs may therefore offer new and attractive opportunities for the management of patients with ali / ards , especially because , to date , no pharmacologic agent has been convincingly shown to improve the prognosis of these patients . the data of kuklin and colleagues suggest that endothelin receptor antagonists might benefit patients with ali / ards . as expected from the use of a receptor antagonist , the level of the ligand increased ; that is , the plasma concentration of endothelin-1 was elevated after tezosentan treatment . as also expected from the proinflammatory properties of endothelin-1 , plasma levels of tnf- and il-8 increased after tezosentan treatment . the clinical relevance of these observations is unknown , but production of these cytokines might counteract the benefits expected from endothelin blockade . in other experimental models of ali / ards , endothelin receptor antagonists did not decrease intrapulmonary shunt , lung lymph flow or the histologically evaluated degree of parenchymal injury , despite a reduction in pulmonary vascular resistance . the work of kuklin and colleagues provides important information on the complex effects of endothelin blockers on inflammatory processes . from a clinical point of view , given the prolific nature of the inflammatory cascade causing ali / ards and the angel / devil effects of endothelin receptor antagonists on inflammatory mechanisms , it is unlikely that these single agents could reverse or terminate such a complex process . ali = acute lung injury ; ards = acute respiratory distress syndrome ; il = interleukin ; tnf- = tumor necrosis factor alpha .

acute lung injury is a syndrome of inflammation and of increased permeability of the blood gas barrier . endothelins are thought to exert proinflammatory effects . kuklin and colleagues show that the endothelin receptor antagonist tezosentan reduces pulmonary edema in endotoxemic sheep , in parallel with a prevention of protein kinase c- activation . in turn , the level of some cytokines increased after tezosentan treatment . whether these contrasting effects of endothelin blockade on inflammatory mechanisms have clinical relevance and whether these agents might benefit patients with acute lung injury is unknown .

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the number of patients undergoing chemotherapy grows year by year . despite their efficacy in controlling the cancer , chemotherapy drugs are not inert , and they cause damage to the human body regarding nail involvement , diverse clinical features can be observed , according to the structure affected and the severity of the damage caused . the most common chemotherapeutic agents implicated in nail changes are cyclophosphamide , doxorubicin and hydroxyurea [ 2 , 3 ] . in the majority of cases , the effects are fully reversible after a few months once the causative agent has been withdrawn [ 2 , 4 ] . a 25-year - old male patient was admitted to the hospital 's hematology ward with the diagnosis of acute lymphocytic leukemia . the hyper - cvad regimen delivers a combination of drugs in 2 cycles ( cyclophosphamide , vincristine , doxorubicin and dexamethasone in cycle a , methotrexate and cytarabine in cycle b ) , split into smaller doses and administered at more frequent intervals in order to minimize side effects . during hospitalization , a dermatology assessment was requested . the dermatological examination showed nail injury characterized by transverse , brown - gray hyperpigmentation affecting the proximal half of the nail plate , with a brown band delimiting the healthy nail plate on all fingers ( fig . 1 , fig chromonychia induced by chemotherapeutic agents has different forms , the most common being melanonychia [ 2 , 4 , 5 ] . the dark pigmentation in nails can be diffuse , transverse or longitudinal and can coexist with skin and mucosal pigmentation [ 2 , 4 , 6 ] . it has been suggested that chemotherapy drug regimens influence the incidence of changes that may result from toxicity in the nail matrix , nail bed , periungual tissue and digits vessels [ 2 , 6 ] . although several chemotherapeutic agents can cause these changes , those most associated with these side effects are cyclophosphamide , doxorubicin and hydroxyurea [ 2 , 3 ] . cyclophosphamide is an alkylating agent whose main target is the cell cycle ; thus , tissues with high proliferation rates are more susceptible . alkylating agents form cross - links with dna filaments and prevent dna replication , therefore entailing cytotoxicity . cyclophosphamide can cause nail changes such as diffuse , black pigmentation , longitudinal striae ranging in color from slate gray to black , and diffuse , dark gray pigmentation located proximally , with overlying transverse , black bands [ 2 , 4 ] . this drug - induced nail pigmentation starts from the proximal edge of the nail and proceeds towards the distal edge . upon withdrawal of the drug it takes approximately 46 months [ 2 , 3 ] . in 60% of patients , cyclophosphamide is also associated with pigmentation of the oral mucosa and tongue , which also regresses upon withdrawal of the drug [ 2 , 4 ] . its side effects include skin and nail hyperpigmentation , alopecia , skin rash , pruritus , photosensitivity , urticaria , acral erythema and palmoplantar erythrodysesthesia . nail changes such as transverse , dark brown bands alternating with white stripes [ 2 , 7 ] and dark brown diffuse pigmentation bands 45 mm wide , which affect two - thirds of the distal portion of the nail , also occur [ 2 , 5 ] . additionally , doxorubicin can cause subungual keratosis , onycholysis and thickening of the nail plate . hydroxyurea causes an immediate inhibition of dna synthesis by acting as an inhibitor of ribonucleotide reductase , without interfering in the synthesis of ribonucleic acid or protein . this pigmentation has a diffuse , dark brown color which may appear as single or double transverse bands [ 2 , 4 ] . ungual hyperpigmentation induced by chemotherapy is not uncommon , although its occurrence is underestimated and seldom reported , especially in patients with dark skin phototypes , such as our patient , in this case , the drugs most probably implicated are doxorubicin and cyclophosphamide because they produce ungual alterations very similar to the ones seen in our patient ; his chemotherapeutic scheme included both of them .

chemotherapy drugs can affect the skin and its appendages . several clinical presentations can be observed , depending on the affected structure . the most common dermatological side effect is chromonychia . the main causative agents are : ( 1 ) cyclophosphamide , which can provoke a diffuse , black pigmentation , longitudinal striae and dark grey pigmentation located proximally on the nails ; ( 2 ) doxorubicin , which promotes dark brown bands alternating with white striae and dark brown pigmentation in transverse bands , and ( 3 ) hydroxyurea , which produces a distal , diffuse , dark brown pigmentation . in the majority of cases , the effects are reversible after the suspension of the causative agent for a few months . we report a patient who developed chromonychia while undergoing treatment with cyclophosphamide , vincristine , doxorubicin , dexamethasone , methotrexate and cytarabine for acute lymphocytic leukemia .

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granuloma annulare ( ga ) was first described in 1895 by colcott - fox who reported an 11-year - old girl with a ring eruption of the fingers . the condition is a benign , usually self - limited granulomatous disease of the dermis and subcutaneous tissue . clinically , the condition is characterized by asymptomatic , flesh - colored or erythematous - brown papules , frequently arranged in a ring or annular pattern on the distal extremities . it may be skin - colored erythematous or violaceous measuring 1 - 5 cm in diameter . several clinical variants of ga have been reported , namely localized , generalized or disseminated , targetoid , giant , subcutaneous and perforating ga . we report an 18-month - old male child with multiple , progressive ga over the lower extremities . an 18-month - old male child presented with multiple annular lesions over lower extremities and buttocks . initially it started as a small papule over the left thigh , substantially attaining the present size . there was no history of fever , pain , drug intake or recent vaccination . on examination , on cutaneous examination , closely set , skin - colored , firm , smooth papules 2 - 3 mm in size arranged in a ring - like fashion to form annular plaques measuring approximately 3 3 cm ( eight lesions ) were present over dorsal aspect of foot [ figures 1 and 2 ] , both legs and buttocks . granuloma annulare over the left foot granuloma annulare over the right ankle routine hematological , biochemical and urine examinations were normal . venereal disease research laboratory test , human immunodeficiency virus 1 and 2 , hepatitis surface antigen test were negative and a biopsy showed features consistent with ga . ga is a benign , relatively common cutaneous disease that classically presents as closely set , skin - colored , firm , smooth papules 2 - 3 mm in size arranged in a ring - like fashion to form annular lesions . most cases occur before the age of 30 years and it is approximately twice more common in females . it often favors sacral sites such as the dorsa of the hands , elbows and feet but involvement of the palms appears to be rare . occasional familial cases are described with the occurrence in twins , siblings , and members of successive generations . attempts to identify an associated hla sub - type have yielded disparate results in different population groups . linear ga , a follicular pustular form and popular umbilicated lesions in children have also been described . the condition manifests as numerous ( at least 10 , often hundreds to thousands ) small , asymptomatic , erythematous , violaceous , brown- or skin - colored papules . rarely , ga may be complicated by nerve involvement as a result of granulomatous inflammation surrounding cutaneous nerves and perineural infiltrates of histiocytes in the dermis . the differential diagnoses of localized ga include tineacorporis , pityriasis rosea , pityriasis rotunda , erythema annulare centrifugum , nummular eczema , discoid lupus erythematosus , psoriasis , necrobiosis lipoidica , morphea , hypertrophic lichen planus and erythema chronicum migrans . treatment options include topical or intralesional corticosteroids , imiquimod cream , topical calcineurin inhibitors ( tacrolimus , pimecrolimus ) , cryotherapy , and pulsed dye laser .

granuloma annulare is a benign , self - limiting , inflammatory and granulomatous disease of unknown etiology occurring in both adults and children . an 18-month - old male child had multiple progressive annular plaques over the lower extremities . clinical and histopathological features were consistent with granuloma annulare . localized granuloma annulare is the most common form in children . we report a young child with multiple , progressive granuloma annulare over the lower extremities .

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a 39-year - old man visited our clinic with a 2-week history of whitening of the eyelashes of his left lower lid . the patient reported that this started with 1 to 2 lashes on the central part of his eyelid and that adjacent eyelashes subsequently became involved over the next few days . otherwise the patient was in excellent health with no significant medical history ; he had no known drug allergies and was on no chronic medications . there was no associated family history of vitiligo , poliosis , or autoimmune disorders such as vkh or sarcoidosis . on examination , a pigmented skin nevus , approximately 4 mm in diameter , was noted above a patch of white eyelashes on the central aspect of the left lower eyelid ( fig . 1 ) . according to the patient , the nevus had existed and remains unchanged since childhood . no other abnormalities of the eyelid were noted and there was no vitiligo or signs of periocular inflammation . his visual acuity was 20/20 in both eyes and there were no significant findings in the anterior segment or fundus . serological tests for autoimmunity ( antinuclear , antimitochondrial , and antismooth muscle antibodies ) were negative and human leukocyte antigen ( hla ) typing failed to demonstrate types hla - dr4 or dw53 excisional biopsy of the central eyelid , including the pigmented nevus and white eyelashes , was performed . on histopathologic examination , the nevus cells appeared unremarkable and showed no evidence of malignancy . marked deficiency of melanocytes in the hair follicles was visible as compared with the normal overlying epidermis ( fig . 2 ) . infiltration of inflammatory cells , including lymphocytes and macrophages , was observed in the dermis ( fig . 3 , the majorities of halo nevi are acquired compound melanocytic nevi and appear in childhood and early adolescence . the site of predilection is the trunk and the back , especially when there are multiple lesions . patients with halo melanocytic nevi usually seek medical attention when their pigmented lesions develop a rim of depigmentation . over time , i , the central nevus remains brown in color or its pigment can disappear leading to a pink - colored papule ( stage ii ) . then the central papule disappears , leading to a circular area of depigmentation ( stage iii ) . finally , the depigmented area may repigment ( stage iv ) , leaving no trace of its existence . the underlying pathophysiology of the halo phenomenon is not well understood , but may possibly be the result of an immune response leading to nevus cell destruction . some authors suggest an autoimmune response directed against antigenic changes of dysplastic nevi while others regard it as an autoimmune phenomenon against melanocytes , as occurs in vitiligo . however , cellular and antibody - mediated immune mechanisms seem to be heavily involved in both theories and it is now well accepted that the inflammatory response is predominantly lymphocytic in nature , often with the addition of a small number of melanophages . there are four histologic forms of halo nevi described : ( a ) inflammatory halo nevus , ( b ) noninflammatory nevus , ( c ) halo nevus without halo or halo nevus phenomenon , and ( d ) halo dermatitis around a melanocytic nevus ( mayerson 's nevus ) . a halo nevus without the halo phenomenon is very rare and can only be diagnosed by histology . . described spontaneous regression of congenital nevi without the development of the halo phenomenon . sotiriadis et al . reported one case of a halo nevus without the halo phenomenon which developed on the trunk of a 5-year - old girl . they reported pathologic findings of a thin epidermis with marked orthokeratotic hyperkeratosis and dense lymphocytic infiltration intermingled with melanocytes ; these findings were consistent with the diagnosis of a halo nevus . a t - cell - mediated autoimmune response leading to melanocyte destruction with resultant poliosis and associated halo nevi in vkh disease however , our case exhibited no evidence of autoimmune disease and no halo phenomenon or vitiligo . in our case only histopathologic findings , such as infiltration of lymphocytes and melanophages , suggested the regression phase of the melanocytic halo nevus . total loss of melanocytes in eyelash follicles may be an isolated sign of the halo phenomenon without depigmentation of the skin . despite an in - depth review of the literature . the only reports of halo nevi of the eyelids were accompanied by vitiligo , not poliosis . also , a case of poliosis with a conjunctival melanoma has been described . one possible , though very unlikely , explanation for the presence of poliosis without skin depigmentation occurring in this case may be a predilection of melanin - rich hair follicles for immunologic reactivity . it is not possible for us to state with certainty why this may have occurred in the setting of a halo nevus undergoing regression , although it is very likely that the inflammation resulted from an exaggerated cell - mediated immune response . in conclusion , we herein present a case of a halo nevus with poliosis of the eyelashes as the only sign of the halo phenomenon . further analysis is needed to elucidate the mechanism of spontaneous regression of a halo nevus without depigmentation .

a 39-year - old man with poliosis of his lower eyelid lashes visited our clinic . he reported that his symptoms began with a few central lashes and then spread along the adjacent lashes during the ensuing 2 weeks . a pigmented nevus , approximately 4 mm in diameter , was identified just above the white lashes without surrounding skin depigmentation . no specific findings were identified with regard to the patient 's general health or serologic and radiologic testing . excisional biopsy of the pigmented nevus was performed . on histopathologic examination , infiltration of the dermis by numerous lymphocytes and melanophages was observed . the poliosis was ultimately diagnosed as a presenting sign of the halo phenomenon in the regressive stage of a melanocytic nevus .

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the most common adverse effects are indigestion , bleeding disorders , rash , diarrhea , and , rarely , taste disorders . here , we report a case of clopidogrel - induced ageusia notified in sfax pharmacovigilance center on march 13 , 2009 . a 46-year - old man was admitted in the department of cardiology in sfax tunisia in january 2009 for coronary artery disease and underwent coronary artery stenting . clopidogrel ( 150 mg / day ) was initiated on january 8 , 2009 , with lysine acetylsalicylate ( one bag / day ) and molsidomine ( 60 mg / day ) . however , the sense of smell was not affected . the ear nose throat ( ent ) examination ruled out abnormality ( dryness , atrophy , or infection ) of buccal mucosa and cranial nerve lesion . it was considered that simvastatin could be responsible for this adverse effect and it was then stopped it is indicated for secondary prevention in patients with atherosclerosis , coronary artery disease , and cerebral event such as transient ischemic attack . the caprie study demonstrated that clopidogrel has a favorable efficacy / safety ratio and provides an additional 8.7% relative - risk reduction for thrombotic events over lysine acetylsalicylate and is safer than ticlopidine . in addition , several other clinical studies have shown that clopidogrel reduces the overall rate of thromboembolic events in patients with recent myocardial infarction , stroke , or peripheral arterial disease compared with aspirin . side effects of new medicines are often not revealed during the initial clinical trials but are discovered when their use becomes a standard of care and , therefore , widespread . indeed , in the present case , an enquiry of pharmacovigilance was done according to french imputation method . besides psychogenic , systemic , oral , and neurological pathologies , medicines are the most common cause of taste disturbance . the fact that a large variety of medications affect the sense of taste is evidence of the complexity of the gustatory systems . the reception , transduction , propagation , and perception of a chemical tasting or odorant require the effective operation of numerous mechanisms . . thus , drug - induced adverse taste effects can reflect the taste of the drug itself , destroy mitosis in a replicating receptor cell , block the apical ion channels on a taste bud as a diuretic , and lead to candidal overgrowth on the tongue surface as immunosuppressants and steroids . these can also inhibit cytochrome p450-dependent enzymes at the level of receptors as an antifungal , disturb neuronal impulse propagation , cause changes in the neurotransmitter function , as well as alter higher order cortical processing of taste - related sensory information , production , and chemical composition of saliva and mucosal elements . the time of appearance of this side effect in the present case was similar to that reported in literature between two to eight weeks . this observation reminds the dose - related mechanism that remit spontaneously after drug discontinuation , albeit sometimes weeks or months after discontinuing a drug . the present case confirms the hypothesis and the suspected causal drug clopidogrel in the genesis of ageusia . although not a life - threatening side effect , loss of taste can produce significant changes in quality of life of a patient . it can lead to loss of appetite , weight , and may require discontinuation of drug administration in already compromised patients .

clopidogrel is prescribed in cardiac and extracardiac vascular diseases . it is generally well tolerated ; however , few cases of taste disorders have been reported . we present a case of clopidogrel - induced ageusia notified in sfax pharmacovigilance center on march 13 , 2009 . a 46-year - old patient developed ageusia with decreased appetite five weeks after starting clopidogrel . other etiologies including ear nose throat ( ent ) examination were ruled out . five months after reduction of clopidogrel dose , ageusia partially decreased . clopidogrel was strongly suspected as a causal drug . according to the french imputation method , score of imputability was considered as plausible ( c2s2 ) i2 . physiopathology of this side effect is not yet understood . however , it seems to be a reversible and dose - related event . although it is not life - threatening , loss of taste can have significant effect on the quality of life of patients .

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historically , presence of heterotopic gastric mucosa in the intestinal tract has never aroused particular interest among clinicians . apart from its occurrence in the meckel s diverticulum , the condition is regarded as clinically insignificant . gastric metaplasia in the duodenum has been described by several authors , however , the significance of its occurrence remains unknown . extensive use of gastroduodenal fibroscopy enabled the authors to obtain biopsies of the duodenal mucosa . this paper will describe the incidence of gastric metaplasia in duodenum in various gastroduodenal diseases and discuss the pathogenetic role of gastric metaplasia in peptic ulcer . the authors obtained two or three pieces of random biopsy specimens from apparently normal mucosa in the anterior wall of duodenal bulb using gastroduodenal fiberscope on 65 subjects . all biopsies were immediately fixed in 10% formalin solution , embedded in paraffin , and 5 mm thick sections were stained with haematoxylin and eosine and pas , as described by mark and drysdale for sharp distinction of gastric metaplasia . the authors attempted to locate the fundic gland in all specimens but failed . consequently , the possibility of gastric heterotopia was excluded . the surface epithelium of gastric mucosa stained strongly with pas reaction contrasting sharply against the duodenal epithelium , where only goblet cells and the brush border disclosed a positive reaction ( fig . duodenal ulcer and prepyloric ulcers are grouped together since they have the same pathogenetic mechanism as proposed by johnson . the gastric ulcer group consisted solely of patients with ulcers located at the body , angle , or proximal antrum : two of the subjects in this group were additionally diagnosed with duodenitis . the incidence of gastric metaplasia according to its underlying diseases gastric metaplasia was not observed in normal subjects with exception to one ( 5.2% ) . in patients with duodenal and/or prepyloric ulcer ( s ) , its incidence was 72.2% , which was higher than in normal controls ( 5.2% ) and those with gastric ulcer ( 36.4% ) , nevertheless the difference lacked statistical significance ( p<.25 ) . three of 7 patients with duodenitis ( 42.8% ) , and one of 8 patients with gastric erosions ( 12.5% ) , had gastric metaplasia . the incidence of gastric metaplasia in the patients with gastic ulcer seemed to be varied according to the location of ulcer . although the number of cases was too low to evaluate it more thoroughly , the incidence of metaplasia was higher ( 66.7% ) in the patients with ulcers located in lower portion of the stomach ( prepyloric and pyloric ) than ulcers located in lower portion of the stomach ( prepyloric and pyloric ) than ulcers located in upper portion of the stomach ( 57.1% in those with ulcers located in angle and proximal antrum : 0% in those with body ulcer ) . the gastric mucosa in the duodenum can be classified into congenital heterotopic gastric mucosa and acquired gastric metaplasia as shown in table 3 . until now , many authors have made the mistake of combining metaplasia and true heterotopic gastric mucosa . since taylor reported earlier ( in 1927 ) two cases of gastric heterotopia in the duodenum , many authors described heterotopic gastric mucosa in duodenum as slightly raised patches consisting of chief cells and parietal cells . as true gastric heterotopia is frequently seen in meckel s diverticulum , and occasionally in rectum and small intestine , it is usually regarded as congenital in origin . the gastric metaplasia , a term which was first suggested by lessels , is an incomplete form of gastric heterotopia , and is composed of foveolar and pyloric gland : it can be identified only with microscopy . the incidence of true gastric heterotopia is suggested to be present in approximately 2% of the population . however , microscopic gastric metaplasia is far more frequently seen than true heterotopia and it is especially common in duodenal ulcer patients . the incidence of gastric metaplasia in duodenal ulcer patients was reported to be 51.9% by johansen , 74.3% by urakami and 72.2% by these authors series , which was quite similar to previous reports . it is unknown whether the gastric metaplasia has a protective role or a harmful effect in the formation of duodenal ulcer . the presence of gastric epithelium in the duodenum could indicate a simple protective response to excessive acid secretion . urakami reported that the gastric metaplasia is less frequent in the active stage of duodenal ulcer , and its incidence increases in the ulcer s healing stage . jochi found that gastric metaplasia was frequently seen in the margin of the ulcer and appeared to occur with the healing process of the ulcer . suzuki divided the gastric metaplasia into three types : foveolar cell metaplasia , parietal cell metaplasia , fully developed fundic gland metaplasia : he reported that each incidence had been 79.2% , 10.4% . and this study was intended only to reveal the incidence of gastric metaplasia in various gastroduodenal disease patients . the study could be expanded to clarify possible relations between acid secretion , stage of peptic ulcer , and stomach cancer .

to investigate the incidence of duodenal gastric metaplasia and its underlying gastric or duodenal diseases , the authors obtained endoscopic biopsy specimens from the duodenal bulb at random sites during endoscopy from 19 normal subjects , 11 patients with gastric ulcer , 18 with duodenal and/or prepyloric ulcer ( s ) , 7 with duodenitis and 8 with gastric erosions . the biopsy specimens were assessed with pas staining to confirm gastric metaplasia.the incidence of duodenal gastric metaplasia was 72.2% in patients with duodenal and/or prepyloric ulcer ( s ) , which contrasted with the patients with gastric ulcers ( 36.4% ) , duodenitis ( 42.9% ) , gastric erosions ( 12.5% ) , and normal subjects ( 5.3%).in conclusion , the results suggest that gastric metaplasia seen predominantly in patients with duodenal ulcer , seems to be related to hyperacidity and it plays some role in the pathogenesis of peptic ulcer in duodenum .

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paget 's disease ( pd ) of bone is a focal , progressive disorder of accelerated bone remodeling and can lead to bone pain and several complications , including deformities , fractures , and secondary osteoarthritis . although the pathophysiology of pd is very complicated and not well known , the primary lesion is the abnormally increased and activated osteoclast in pd . bisphosphonates , which is the most potent anti - resorptive drug , have been the most effective agents available for the treatment of pd . among the bisphosphonates for osteoporosis treatment , zoledronate is a nitrogen - bound intravenous bisphosphonate with highest potency and longest administration interval . we reported a patient with pd , who had inadequate responses to therapy with pamidronate , has had a clinical remission with intravenous zoledronate . in may , 2010 , a 49-year - old woman presented with 4 year history of both buttock pain . iu / l ( reference range , 30 to 115 iu / l ) . a bone scan , which undergone at outside hospital 4 year ago , confirmed pagetic changes in the left ilium ( fig . 1 ) . and , pelvis anterior - posterior radiograph obtained at our hospital revealed a typical mosaic pattern of pd in her pubic and left ilium ( fig . her weight was 61.4 kg , height was 162 cm , and body mass index was 23.4 kg / m . range of motion at left hip was decreased due to pain , and she walked with a mild limp . although the level of alp was within reference range , pamidronate treatment was started orally for 3 months , because she had a severe pain . however , her pain intensity level increased . iu / l , and bone scan show still hot uptake in her both ilium and lumbar vertebrae ( fig . subsequently , she received intravenous zoledronate ( 5 mg ) in a single dose at august , 2010 . after this treatment , we evaluated clinical and biochemical remission and improvement in bone scan . three months after administration zoledronate , alp decreased 26 iu / l , and a severe pain and limping gait disappeared . six months after intravenous zoledronate , alp decreased 21 u / l , and bone scan showed the improvement , which means a response of zoledronate ( fig . iu / l , and bone scan showed hot uptake in both ilium and lumbar vertebrae ( fig . we report a patient with pd of bone , resistant to pamidronate treatment in whom intravenous zoledronate produced clinical remission and an improvement in the bone scan during 3 years . in united states population over 55 years , the incidence of pd is estimated to approximately 2 - 5% . however , the incidence is very low , and had not been well - known in korea . serum alp is an indicator of osteoblast activity and the primary marker for assessment of pd . however , this patient had low alp at initial presentation , which can not allow physician to suspect pd by a screening laboratory profile . bone scan can be used as a complementary method to diagnose and monitor the activity of pd . recent treatment guidelines recommend an use of bisphosphonate for pd to prevent disease progression and associated - complications , even in asymptomatic patients , especially with critical anatomic location such as skull , spine , weight - bearing bones , or the acetabular regions . oral bisphosphonate has been traditionally used for this , but compliance of oral bisphosphonate is too low , because of complex ingesting methods and gastro - esophageal irritation . therefore , annually intravenous zoledronate could be alternative optional . a clinical trial reported that a single 5 mg zoledronic acid infusion normalized alp levels in 89% of patients , compared with 58% in the control group administered oral risedronate , 30 mg / day for 60 for 2 months . although advantages of zoledronate include the convenience of a 15 minute infusion , approximately 40% of patients experienced zoledronate - associated symptoms ( flu - like illness , pyrexia , myalgia , arthralgia , bone pain ) , typically within the first 3 days after the infusion , with most symptoms resolving within 3 days after onset . this case study demonstrated that a patient with pd who had been treated unsuccessfully with oral bisphosphonates was effectively treated with a 5 mg infusion of zoledronate . the ability of zoledronate to provide a sustained remission offers many advantages for patients with pd and may lead to considerable benefits for the long term in preventing or minimizing complications .

paget 's disease ( pd ) of bone is characterized by increase of bone resorption by atypical osteoclasts , followed by rapid new bone formation resulting in a disorganized mosaic bone . although the pathophysiology is not fully understood , bisphosphonate , which is a potent anti - resorptive agent for treatment of osteoporosis , have been the most effective agents available for the treatment of pd . we report a case of pd of bone in a 49-year - old woman patient , who was treated with intravenous zoledronate .

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a. azurea was proposed by omura et al . in 1983 and later on emended by henssen et al . in 1987 and was isolated from soil that produced two water soluble antibiotics , namely , azureomycin a and b. a. azurea strain dsm 43854 was obtained from the open collection of the german collection of microorganisms and cell cultures ( dsmz ) , braunschweig , germany . the strain a. azurea dsm 43854 is a gram - positive bacteria and contains aerial mycelium with white to blue color . genomic dna was extracted from a 48 hour old culture using zr fungal / bacterial dna miniprep as per manufacturer 's instructions . sequencing resulted in 22,170,928 paired - end reads ( insert size of 350 bp ) of 101 bp length . a total of 21,919,041 high - quality reads with approximately 480 coverage were assembled using clcbio wb5.5 ( http://www.clcbio.com ) ( word size 55 and bubble size 60 ) to obtain 154 contigs ( n50 , 127,182 bp ) . the functional annotation was carried out by rast ( rapid annotation using subsystem technology ) , trna was predicted by trnascan - se-1.23 and rrna genes by rnammer 1.2 . the genome contains 3 rrna genes ( 5s23s16s ) and 58 aminoacyl - trna synthetase genes . the draft genome of a. azurea consists 154 contigs of 9,223,451 bp with an average g + c content of 69.0% . a total of 8603 coding regions ( 4406 from a positive strand and 4197 from a negative strand ) were found in the genome of which 5396 ( 63% ) could be functionally annotated . the genome coding density is 89% with an average gene length of 948 bp . the annotated genome has 117 genes involved in virulence , disease and defense including 61 genes for resistance to antibiotics and toxic compounds such as tetracycline , vancomycin , arsenic and beta - lactamase ( fig . the genome comprises of 55 genes for sulfur metabolism and 47 genes for phosphorus metabolism . the homology searches revealed that the pks gene clusters are supposed to be responsible for the biosynthesis of naptomycin , macbecin , rifamycin , mitomycin , maduropeptin enediyne , neocarzinostatin enediyne , c-1027 enediyne , calicheamicin enediyne , landomycin , simocyclinone , medermycin , granaticin , polyketomycin , teicoplanin , balhimycin , vancomycin , staurosporine , rubradirin and complestatin . the functional comparison of genome sequences available on the rast server revealed the closest neighbors of a. azurea as actinosynnema mirum dsm 43827 ( score 536 ) followed by streptomyces sp . aa4 ( score 432 ) , saccharomonospora viridis dsm 43017 ( score 376 ) and rhodococcus jostii rha1 ( score 357 ) . a. azurea was proposed by omura et al . in 1983 and later on emended by henssen et al . in 1987 and was isolated from soil that produced two water soluble antibiotics , namely , azureomycin a and b. a. azurea strain dsm 43854 was obtained from the open collection of the german collection of microorganisms and cell cultures ( dsmz ) , braunschweig , germany . the strain a. azurea dsm 43854 is a gram - positive bacteria and contains aerial mycelium with white to blue color . genomic dna was extracted from a 48 hour old culture using zr fungal / bacterial dna miniprep as per manufacturer 's instructions . sequencing resulted in 22,170,928 paired - end reads ( insert size of 350 bp ) of 101 bp length . a total of 21,919,041 high - quality reads with approximately 480 coverage were assembled using clcbio wb5.5 ( http://www.clcbio.com ) ( word size 55 and bubble size 60 ) to obtain 154 contigs ( n50 , 127,182 bp ) . the functional annotation was carried out by rast ( rapid annotation using subsystem technology ) , trna was predicted by trnascan - se-1.23 and rrna genes by rnammer 1.2 . the genome contains 3 rrna genes ( 5s23s16s ) and 58 aminoacyl - trna synthetase genes . the draft genome of a. azurea consists 154 contigs of 9,223,451 bp with an average g + c content of 69.0% . a total of 8603 coding regions ( 4406 from a positive strand and 4197 from a negative strand ) were found in the genome of which 5396 ( 63% ) could be functionally annotated . the genome coding density is 89% with an average gene length of 948 bp . the annotated genome has 117 genes involved in virulence , disease and defense including 61 genes for resistance to antibiotics and toxic compounds such as tetracycline , vancomycin , arsenic and beta - lactamase ( fig . the genome comprises of 55 genes for sulfur metabolism and 47 genes for phosphorus metabolism . the homology searches revealed that the pks gene clusters are supposed to be responsible for the biosynthesis of naptomycin , macbecin , rifamycin , mitomycin , maduropeptin enediyne , neocarzinostatin enediyne , c-1027 enediyne , calicheamicin enediyne , landomycin , simocyclinone , medermycin , granaticin , polyketomycin , teicoplanin , balhimycin , vancomycin , staurosporine , rubradirin and complestatin . the functional comparison of genome sequences available on the rast server revealed the closest neighbors of a. azurea as actinosynnema mirum dsm 43827 ( score 536 ) followed by streptomyces sp . aa4 ( score 432 ) , saccharomonospora viridis dsm 43017 ( score 376 ) and rhodococcus jostii rha1 ( score 357 ) . the a. azurea dsm 43854 whole genome shot gun ( wgs ) project has been deposited at ddbj / embl / genbank under the project accession number anmg00000000 of the project ( 01 ) and has the accession numbers anmg01000000 and consists of sequences anmg01000001anmg01000154 . the authors declare that there is no conflict of interest on any work published in this paper .

we report the 9.2 mb genome of the azureomycin a and b antibiotic producing strain amycolatopsis azurea isolated from a japanese soil sample . the draft genome of strain dsm 43854 t consists of 9,223,451 bp with a g + c content of 69.0% and the genome contains 3 rrna genes ( 5s23s16s ) and 58 aminoacyl - trna synthetase genes . the homology searches revealed that the pks gene clusters are supposed to be responsible for the biosynthesis of naptomycin , macbecin , rifamycin , mitomycin , maduropeptin enediyne , neocarzinostatin enediyne , c-1027 enediyne , calicheamicin enediyne , landomycin , simocyclinone , medermycin , granaticin , polyketomycin , teicoplanin , balhimycin , vancomycin , staurosporine , rubradirin and complestatin .

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children constitute approximately 40% of india 's population but information on adverse drug reactions occurring in them is limited . phenytoin sodium ( pht ) is one of the commonest antiepileptic drug ( aed ) used in children in india . the drug has wide pharmacokinetic variability and has a narrow therapeutic range that leads to toxicity . there is some evidence of the association of long - term use of pht and toxicity like cerebellar atrophy . such cerebellar changes have been reported even with the long - term use of nontoxic levels of phenytoin . , we report a case of reversible cerebellar atrophy induced by pht in a 10-year - old boy . after initiating therapy with pht 10 years back , he was seizure free for 2 years . patient was also occasionally prescribed clobazam , 5 mg , oral , as and when required . the episodes used to last for a brief period of over 6 - 7 days . seizures used to occur at every 3 - 4 months interval . the boy had history of birth asphyxia and delay in developmental milestones . after the patient recovered , he was evaluated again due to complaint of difficulty in walking . cns examination revealed normal mentation with cerebellar signs including gaze - evoked nystagamus , truncal , and appendicular ataxia . mri scan of the brain was advised and it showed cerebellar atrophy as shown in figure 1 . serum phenytoin level was high ( 30 mcg / ml ) and pht was withdrawn immediately . patient was started on valproic acid and followed up . however , a sizeable proportion of patients may develop drug induced adverse effects that include sedation , gum hypertrophy , lymphadenopathy , chorea , ataxia , etc . there are a few reports on cerebellar atrophy after long - term use of pth . these adverse effects are usually reported if the drug serum levels are above the therapeutic range . our patient presented with severe cerebellar disorder and he was on the drug for 10 years . hence , a regular monitoring for adverse drug reaction should be considered in patients who are on drugs on long term basis . these reactions could be idiosyncratic or dose - dependent which again may be acute or chronic in nature . since most of these effects are reversible , it is important to identify the clinical manifestations related to drug toxicity and to manage them appropriately . also , it warns the need for regular monitoring of plasma concentration , accurate dosing , and identification of adherence issues in patients on phenytoin .

epilepsy is an important health problem due to its high prevalence and potential for causing long - term morbidity . it is commonly treated in children with phenytoin sodium . it has wide pharmacokinetic variability and a narrow therapeutic range that leads to toxicity . here , we report a case of phenytoin - induced cerebellar atrophy in a 16-year - old epileptic boy who presented to the hospital with a viral infection .

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the natural history for these hernias is progressive enlargement if left untreated and many of these patients undergo elective repair with synthetic mesh for symptomatic or cosmetic reasons . also , the sequelae of potential complications , such as bowel incarceration or strangulation , result in greater morbidity and mortality in cirrhotic patients . this case report discusses one of such patients , who presented with eviscerated bowel through a long - standing umbilical hernia and describes the surgical management employed . a 50-year - old caucasian male with a long - standing history of cirrhosis , secondary to chronic alcohol abuse and hepatitis c infection , presented to the emergency department with evisceration of his small bowel through an existing umbilical hernia ( fig . 1 ) . the patient had a complicated course of liver disease marked by recurrent ascites and hepatic encephalopathy . two years prior , the patient had his umbilical hernia primarily repaired ; however , he developed a recurrence of the umbilical hernia secondary to recurrent and refractory ascites . the patient stated that he suddenly noticed protrusion of bowel through his umbilical skin after a sudden coughing bout several hours prior to presentation . the patient also reported copious drainage of ascitic fluid through the hernia site following the evisceration . following his surgery , the patient spent 7 days in the icu after which he was transferred to a medical surgical floor and subsequently discharged with normal bowel function and in stable condition . patients with ascites in the setting of cirrhosis have an 20% chance of developing an umbilical hernia . in the presence of persistently increased intra - abdominal pressure , points of weakness in the abdominal wall are potential sites of herniation . the linea alba is discontinuous at the umbilicus and thus is one point of weakness . furthermore , this patient had an albumin level of 1.8 g / dl suggesting chronic nutritional deficits that could potentially lead to weakened abdominal fascia . evisceration of small bowel through an existing umbilical hernia is a rare and potentially fatal complication of umbilical hernia in the presence of recurrent ascites . there is a reported case of omental evisceration through an umbilical hernia in a patient with a similar history of cirrhosis and hepatitis c . similar to our patient , this occurred following an acute increase in intra - abdominal pressure . evisceration of abdominal contents puts the patient at risk for incarceration , infection and necrosis . a 2011 study performed by erasmus university researchers found that surgical repair of an umbilical hernia in a patient with ascites due to cirrhosis is preferable to conservative treatment . the complications of the umbilical hernia appear to be a greater cause of mortality and morbidity than the surgical repair . in summary , small bowel evisceration is a rare but serious and potentially fatal complication of umbilical hernia in cirrhotic patients with refractory ascites . this case is the first - in - literature depicting spontaneous evisceration of bowel in a cirrhotic patient with a recurrent umbilical hernia .

umbilical hernia in the cirrhotic patient is frequently seen in the setting of refractory ascites . this article reports a rare case of spontaneous rupture of a recurrent umbilical hernia in a patient with persistent ascites , following an acute increase in intra - abdominal pressure , leading to bowel evisceration . this case highlights a potentially fatal complication of umbilical hernia in the setting of chronic ascites , which was successfully managed with prompt surgical intervention .

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all authors of this article declare that they qualify for authorship as defined by icmje http://www.icmje.org/#author . each author has participated sufficiently in the study and take public responsibility for appropriate portions of the content of this article . as this is a case report without patient identifiers , approval from institutional review board ( irb ) is not required at our institution . to ensure the integrity and highest quality of cytojournal publications , the review process of this manuscript was conducted under a double blind model ( authors are blinded for reviewers and vice versa ) through automatic online system .

alveolar rhabdomyosarcoma is an uncommon tumor affecting adolescents and young adults that is only rarely encountered in body fluid cytology . we report the cytological features of metastatic alveolar rhabdomyosarcoma in the ascitic fluid of a 17-year - old female patient , who had presented with abdominal distention , 21 months after being diagnosed with perirectal alveolar rhabdomyosarcoma . the rare single neoplastic cells that were admixed with abundant reactive mesothelial cells were initially misinterpreted as reactive mesothelial cells . however , their neoplastic nature was established after a careful review of their cytological features and the performance of immunoperoxidase stains . compared to the reactive mesothelial cells that were present in the sample , the malignant cells were smaller , with less ample and more homogenous cytoplasm . they had slightly larger , more hyperchromatic , and more frequently eccentric nuclei , with larger nucleoli . this case highlights the potential pitfall of the misinterpretation of metastatic alveolar rhabdomyosarcoma cells for reactive mesothelial cells . awareness of this potential diagnostic problem and recognition of the cytomorphological features of this neoplasm in the body fluids allows the identification of malignant cells , even when they are rare and intimately associated with mesothelial cells .

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the most frequent sites of bleeding in patients with haemophilia are the soft tissues , the joints , the urinary tract , but much more rarely the gastrointestinal tract . the complications of intramural bleeding are acute intestinal obstruction , but also rupture of the haematoma in the lumen or the peritoneal space . we present the case of a haemophiliac patient who was admitted as an emergency due to distended abdomen , nausea , vomiting and the clinical picture of ileus . the native abdomen in a standing position presented air fluid levels with moderate distension of the accompanying bowel loops . a nasal probe was inserted and the symptoms of ileus disappeared , but after taking food by mouth , the picture of ileus returned . ct of the abdomen and pelvis was performed , which showed circular , high density thickening of the walls in places in the area of the jejunum , indicating haemorrhage , but also the formation of haematoma in the wall structure . after administering factor viii , the symptoms of ileus ceased , and the patient recovered completely . this unusual presentation of haemophilia with bleeding in the wall of the small intestine is very rare and has only been seen in a few cases in the world . ct diagnosis defined the cause of the obstruction and saved the patient from an unnecessary surgical procedure . haemophilia is a congenital blood ailment characterized by the lack of coagulating factor viii ( haemophilia a ) or factor iv ( haemophilia b ) . the most frequent sites of bleeding are the soft tissue , the joints , the urinary tract , and much more rarely the gastrointestinal tract ( 1 ) . gastrointestinal haemorrhage has an incidence of 17.525% in haemophiliacs and causes death in 4% of this population overall ( 2 ) . the complications of intramural bleeding are acute intestinal obstruction , but also the rupture of the haematoma in the lumen or in the peritoneal space ( 3 ) . this case presents a patient with haemophiliac ileus of the small intestine , where ct diagnostics defined the cause of the obstruction and saved the patient unnecessary surgery . the patient was admitted in the evening as an emergency case , due to a distended abdomen , nausea , vomiting and the clinical picture of ileus . the native abdomen in a standing position presented air fluid levels with moderate distension of the relevant bowel loops ( figure 1 ) . a nasal probe was inserted and the symptoms of ileus disappeared , but after taking food by mouth , the picture of ileus returned . laboratory test results : wbc 11/00 , rbc 6.35 , hct 0.503 , hgb 166 . a - ptt 84.8 ( rv:26 - 28 s ) , antihaemophilic factor a ( ahg - a ) , f - viii < 0.05 ( rv:0.7 - 1.5 j ) . ct of the abdomen and pelvis was performed , which showed circular high density thickening of the walls in places in the area of the jejunum , indicating haemorrhage , but also the formation of haematoma in the wall structure . the presence in places of air fluid levels suggested disturbed passage through the bowels ( figures 2 and 3 ) . in the area of the jejunum circular high density thickening of the walls in places , indicating haemorrhage , but also the formation of haematoma in the wall structure . after administering factor bleeding in the gastrointestinal tract in haemophiliacs is not rare , and is usually manifest either in melena or per rectum . bleeding less often occurs in the intestinal wall , with the symptoms of intestinal obstruction . in this case , intramural bleeding had occurred in the small intestine ( figure 2 ) and the intramural haematoma was the cause of paralytic ileus and intestinal obstruction . the most probable physiopathology of intramural haematomas of the bowel is characterized by the spread of the terminal arterial vessels as they leave the mesentery and penetrate the muscular layer of the intestinal wall ( 3 ) . an intramural haematoma may also cause intussusception , as another form of ileus ( 4 ) . as bleeding is the most frequent cause of acute abdominal pain in haemophiliacs , an acute abdomen should be deemed to be bleeding , until proven otherwise by diagnostic methods ( ct ) . it is a very useful method in diagnosing intramural haematoma , defining the area of the haemorrhage and revealing possible complications . most intramural haematomas can be treated conservatively and spontaneous resolution occurs , where bleeding is treated by prompt compensation of factor viii . correct diagnosis and a multi - discipline approach are imperative in order to avoid unnecessary explorative procedures .

introduction : the most frequent sites of bleeding in patients with haemophilia are the soft tissues , the joints , the urinary tract , but much more rarely the gastrointestinal tract . the complications of intramural bleeding are acute intestinal obstruction , but also rupture of the haematoma in the lumen or the peritoneal space.case report : we present the case of a haemophiliac patient who was admitted as an emergency due to distended abdomen , nausea , vomiting and the clinical picture of ileus . the native abdomen in a standing position presented air fluid levels with moderate distension of the accompanying bowel loops . a nasal probe was inserted and the symptoms of ileus disappeared , but after taking food by mouth , the picture of ileus returned . ct of the abdomen and pelvis was performed , which showed circular , high density thickening of the walls in places in the area of the jejunum , indicating haemorrhage , but also the formation of haematoma in the wall structure . after administering factor viii , the symptoms of ileus ceased , and the patient recovered completely.conclusion:this unusual presentation of haemophilia with bleeding in the wall of the small intestine is very rare and has only been seen in a few cases in the world . ct diagnosis defined the cause of the obstruction and saved the patient from an unnecessary surgical procedure .

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cirrhosis is characterized by circulatory changes corresponding to a hyperkinetic state with arterial vasodilatation , decreased systemic vascular resistance , and increased cardiac output . hyperkinetic state and vasodilatation worsen in parallel with the deterioration in liver function . in patients with end - stage cirrhosis , arteriolar vasodilatation is no longer compensated by an increase in cardiac output , resulting in a state of arterial underfilling . arterial underfilling , in turn , results in the activation of vasoconstrictor systems , which causes intense intrarenal vasoconstriction and a marked decrease in glomerular filtration rate ( gfr ) and eventually leads to hepatorenal syndrome ( hrs ) . the increase in creatinine can be abrupt ( type i hrs ) or follow a more progressive course ( type ii hrs ) . a first set of criteria had been proposed in the mid-'90s to better differentiate hrs from other causes of acute renal failure in cirrhosis , the absence of improvement with volume expansion being central in the definition of hrs . however , these criteria proved to be too restrictive . for instance , ongoing bacterial infection was considered an exclusion criterion although experience shows that hrs frequently is triggered by infections . the diagnostic criteria were revisited in 2007 in order to be less restrictive . however , these criteria still have some limitations . firstly , it has been shown that a substantial proportion of patients who are undergoing transjugular renal biopsy and who have a clinical diagnosis of hrs do have intrinsic kidney changes , especially tubulointerstitial injury resulting from either comorbidities or chronic ischemia . secondly , the limit of a creatinine level of more than 1.5 mg / dl to define hrs may be inappropriate . indeed , owing to muscle wasting , some cirrhotic patients with a serum creatinine level of below 1 mg / dl may already have a marked decrease in true gfr . in the previous issue of critical care , a group of experts , including not only hepatologists but also nephrologists and intensivists , reported the results of a workshop aimed at reviewing current knowledge in the field of hrs and proposing new classifications , based on the widely used rifle ( risk , injury , failure , loss , and end - stage kidney disease ) criteria , of all forms of renal impairment in cirrhosis . the group proposed the term ' hepatorenal disorder ' to define any kind of kidney disease that is functional or structural in nature in patients with cirrhosis . acute kidney injury is considered at an earlier stage in patients with a creatinine increase of at least 0.3 mg / dl within 48 hours and/or a 1.5 or more increase in creatinine from baseline . this new classification may help initiate specific therapy at an earlier stage and increase the chance for recovery . this classification is also more appropriate to identify any kind of kidney injury within a wide spectrum of causes of acute , chronic , and acute - on - chronic kidney diseases in cirrhosis . however , even if the patients are identified at an earlier stage , the revised classification does not clearly differentiate those who may benefit from medical therapies of hrs ( that is , terlipressin or noradrenaline ) from those who may not . in addition , this classification does not help address the important issue of reversibility after liver transplantation . in most western countries , the model for end - stage liver disease ( meld ) score determines priority for allocation in liver transplantation . since creatinine is one of the three components of the meld score ( along with bilirubin and international normalized ratio ) , the proportion of patients undergoing liver transplantation with renal insufficiency has significantly increased in the meld era . the rate of post - transplant chronic renal failure has also increased with a 5-year cumulative incidence that may exceed 20% . finally , the number of combined liver and kidney transplantations has also increased with declining outcomes , raising the issue of overuse and misuse in combined transplantation . overall , circulatory changes in cirrhosis necessarily have a deleterious impact on the course of any chronic kidney disease , regardless of the cause and mechanisms . a challenging issue is to determine more accurately the potential for improvement with liver transplantation alone , by reversing hyperkinetic state , in order to better identify those who need a combined liver and kidney transplantation and those who do not . in theory , hrs is a functional disorder that is fully reversible with liver transplantation . however , as discussed above , a number of patients with hrs have intrinsic kidney changes that may not improve after transplantation . therefore , another issue is to better identify the subgroup of hrs patients who are likely to rapidly develop end - stage renal failure after transplantation . unfortunately , in patients who have end - stage cirrhosis complicated by hrs and who are not candidates for transplantation , therapies such as terlipressin or albumin dialysis provide only a modest survival benefit . in the majority gfr : glomerular filtration rate ; hrs : hepatorenal syndrome ; meld : model for end - stage liver disease .

hepatorenal syndrome ( hrs ) is a pre - renal azotemia - like acute renal failure occurring in patients with end - stage cirrhosis . hrs results from arteriolar vasodilatation , arteriolar underfilling , and intense renal vasoconstriction . by definition , it is not responsive to volume expansion , and the prognosis is especially poor even with the use of terlipressin or albumin dialysis or both . it may be difficult , on the basis of the current criteria , to clearly differentiate hrs from other causes of acute renal failure in cirrhosis . in addition , patients with hrs frequently have underlying chronic kidney changes that may not be reversible after transplantation . in the previous issue of critical care , a group of experts proposed a new classification of acute , acute - on - chronic , or chronic renal impairment in cirrhosis on the basis of the rifle ( risk , injury , failure , loss , and end - stage kidney disease ) criteria . the group proposed the term ' hepatorenal disorder ' to define patients with advanced cirrhosis and kidney dysfunction at an earlier stage , regardless of the mechanisms . as stated by the authors , more data are needed to clearly identify , by non - invasive means , those with a potential for improvement with liver transplantation and those who can undergo a combined liver and kidney transplantation .

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primary cysts have no clear aetiology and tend to arise spontaneously , while secondary cysts result from a known aetiology such as trauma , surgery or medications [ 1 , 2 ] . primary iris cysts may arise from either the iris pigment epithelium ( ipe ) or the iris stroma [ 2 , 3 ] . in rare instances , an ipe cyst may dislodge and pass from the posterior chamber through the pupil , resulting in a free - floating cyst in the anterior chamber . we describe such a case , where a free - floating iris cyst within the anterior chamber was observed in the setting of recurrent iritis . we also discuss the complications , significance of iritis and management of free - floating iris cysts . a 39-year - old male with a 5-year history of mild recurrent iritis ( 6 episodes ) affecting the right eye was found to have a free - floating iris cyst of approximately 0.5 by 0.8 mm within his right anterior chamber ( fig . mobilisation of the cyst occurred with head tilt but never caused pain or visual compromise ( fig . there were small fluctuations in the size of the iris cyst but no gross or rapid enlargement . his past medical history included reactive arthritis , and he tested positive for hla - b27 . there was no past history of ocular surgery or trauma , and no family history of ocular disease . all episodes of mild iritis affected the anterior segment only and were treated effectively with dexamethasone ophthalmic drops for 26 weeks . he did not have keratic precipitates on his corneal endothelium , anterior or posterior synechiae . the differential diagnosis includes iris stromal cyst , iris or ciliary body melanoma , adenoma of the ipe and medulloepithelioma . ipe cysts have been associated with ocular complications such as angle closure glaucoma , plateau iris syndrome , and secondary pigment dispersion syndrome . however , these complications are uncommon . a case series of 234 patients found that none of the ipe cysts grew larger after a mean follow - up period of 35 months . in particular , no visual or ocular complications were reported in patients with free - floating iris cysts . a study of 62 patients sought to determine current or prior ocular disorders associated with iris cysts [ 1 , 7 ] . four patients had a history of iritis ; however , ocular inflammation was either mild or in remission in 3 of the 4 patients [ 1 , 7 ] . only 1 patient presented with severe iritis and a large iris cyst , which regressed in size upon resolution of the iritis . in another study of 14 patients with iritis , 3 patients showed evidence of new iris cyst formation . this suggests that ocular inflammatory disorders may contribute to the development of iris cysts or cause pre - existing cysts to enlarge . however , the paucity of further evidence means that the full extent of this relationship remains theoretical . in our patient we could not find an association between the small fluctuations in the size of the iris cyst and his episodes of iritis . asymptomatic non - progressive iris cysts are best left alone , and the indications for surgical removal include significant visual disturbances , rapid increase in cyst size over a short period of time , evidence of recurrent iridocyclitis , corneal endothelial touch by the cyst or secondary glaucoma [ 3 , 5 ] . the use of neodymium - doped yttrium aluminium garnet laser to collapse the iris cyst has also shown favourable results in symptomatic patients [ 3 , 9 , 10 ] . our patient remained asymptomatic ; thus , surgical removal or laser treatment was not warranted . few have been implicated in causing visual disturbance or ocular complications , warranting their removal . the paucity of available evidence means that the association between recurrent iritis and the development or progression of free - floating iris cysts remains inconclusive .

purposewe describe an unusual clinical finding of a free - floating iris cyst in a patient with recurrent iritis.methodthe clinical finding of a free - floating iris cyst was recorded using slit - lamp photography.resultsa 39-year - old male with a 5-year history of recurrent right iritis was found to have a small mobile iris cyst within his right anterior chamber , first identified 3 years ago . the patient did not experience any discomfort or visual symptoms resulting from the cyst.conclusionsurgical removal is not indicated for asymptomatic non - progressive free - floating iris cysts . the significance of a free - floating iris cyst in the setting of recurrent iritis remains unknown .

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some other causes can be due to postoperative adhesions , duplication cyst , meconium ileus , and internal hernia . according to our knowledge , this is the first report of intrauterine volvulus of terminal ileum without malrotation that was diagnosed by ultrasound . our case deals with terminal ileum torsion around its axis with twisting of mesenteric vessels . therefore , it is of medical importance to recognize the radiological signs of bowel torsion as soon as possible . we present a case of volvulus of terminal ileum which was diagnosed and treated surgically in a neonate just 15 h after delivery . a female baby was born preterm at 35-weeks , with parameters appropriate for her gestational age , weighing 2666 g , with apgar 9 - 10 at 1 and 10 min , respectively . maternal history provided a previous missed abortion , otherwise the mother was a healthy woman who had a normal pregnancy and normal fetal screening follow - up findings . on physical examination of the preterm baby investigational work - up was started including , chest x - ray which was normal , arterial blood gases showed mild metabolic acidosis , blood and urine culture were obtained , and wide spectrum intravenous antibiotics were started . the baby was referred to our radiological department for plain abdominal x - ray at age of 2 h. the x - ray showed a distended and gasless abdomen , except for a small amount of air in the stomach [ figure 1 ] . female baby at 2 h after birth with distended abdomen diagnosed with intrauterine volvulus of terminal ileum without malrotation . x - ray of abdomen shows distended and gasless abdomen except a small amount of air in the stomach ( black arrow ) . this radiological finding might be normal at this age , but since the baby was crying it was assumed to have more air in the intestine . thus , we started an upper gastrointestinal study to rule out any cause of intestinal obstruction . the barium study ruled out a malrotation showing a normal gastric , duodenal , and normal location of the treitz ligament [ figure 2 ] . two hours after the start of the barium study , we noticed lack of propagation of the barium at the level of right lower quadrant of the abdomen . this led us to suspect ileal atresia , which is the most common cause of obstruction after malrotation . sign with filling defect and a round structure around this end loop [ figure 3 ] . this radiological finding suggested ileal obstruction due to volvulus with presumed duplication cyst as the leading point . female baby at 2 h after birth with distended abdomen diagnosed with intrauterine volvulus of terminal ileum without malrotation . female baby at 13 h after birth with distended abdomen diagnosed with intrauterine volvulus of terminal ileum without malrotation . at 13 h , the barium study shows stopage of barium with a beak - like shape of the pre - obstructed bowel ( black arrow ) with filling defect(white arrow ) and a structure containing air around the end loop ( arrowheads ) immediate ultrasonographic examination of the abdomen was done to confirm the diagnosis . ultrasound scan showed a target lesion consistent of two loops of bowel , pneumatosis of the bowel wall , and twisting of vessels [ figure 4 ] , suggesting a diagnosis of ileal volvulus with intestinal ischemia . intraoperative findings showed volvulus of terminal ileum with intestinal ischemia and perforation with free meconium in the abdomen . we think that meconium in this case was the main predisposing factor for the volvulus of this baby . female baby at 13 h after birth with distended abdomen diagnosed with intrauterine volvulus of terminal ileum without malrotation . ultrasonographic examination of the abdomen shows a target lesion consistent with two loops of bowel , pneumatosis of the bowel wall ( arrowheads ) and twisting of vessels ( white arrow ) . according to our knowledge , this is the first case of intrauterine volvulus of terminal ileum without malrotation , that was diagnosed definitively by ultrasound and operated on within a few hours after birth thus saving the life of the baby . neonatal volvulus is secondary to malrotation , and involves twisting of bowel loop with its feeding vessels that leads to ischemia , necrosis , and perforation with fatal complication , if not recognized and treated in time . however , other rare predisposing causes are meckel 's diverticulum , duplication cyst , and meconium plug . diagnosis of volvulus in any suspected neonatal intestinal obstruction by plain film and barium study is extremely difficult especially when malrotation is ruled out . the most common causes of these cases of intestinal obstruction are intestinal atresia that is fatal in the first hours of life if not treated immediately . based on our case , we suggest : in any case of suspected intestinal obstruction , first we have to rule out intestinal malrotation with an upper gastrointestinal barium study . once malrotation is ruled out , we suggest immediately performing an ultrasound examination of the abdomen to rule out an ileal volvulus . thus , ultrasound examination that shows a target lesion bird beak sign of the involved bowel allows to quickly identify this morbid entity without loss of precious time .

neonatal terminal ileum volvulus in the absence of malrotation has never been reported before in english literature . however , another similar rare entity known as neonatal primary segmental volvulus without malrotation has been reported before . volvulus , in general , is an extreme emergency and cases not diagnosed in time lead to death . the main diagnosis is based on radiological features seen on imaging . we present a case of volvulus of terminal ileum that was diagnosed and surgically treated at age of 15 h ensuring the newborn survived . the definitive diagnosis was based mainly on ultrasonographic findings .

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pelvic digits are rare congenital anomalies that develop in soft tissue.(1 - 4 ) there are less than twenty reported cases in the literature . the majority of reported pelvic digits are asymptomatic and found incidentally during radiography.(2 ) to date , there has never been a report describing a patient with a pelvic digit who presents with a chief complaint of dyspareunia . to the best of our knowledge , this is the third reported case of a symptomatic pelvic digit and emphasizes the importance of considering lesions of the bony pelvis in the differential diagnosis of dyspareunia . a 57-year - old caucasian female presented with a chief complaint of more than one year of dyspareunia . her past medical history includes chronic bilateral knee , hip and ankle pain and had a right total hip arthroplasty that required multiple revisions . she had no pain with hip range of motion and her motor and sensory examinations were intact . review of her radiographs demonstrated a well - positioned right total hip arthroplasty without any evidence of loosening or wear . however , there was an osseous growth projecting from the inferior aspect of left ischium toward the perineal region . additional imaging with computed tomography ( ct ) and non contrast magnetic resonance ( mr ) were used to further define the lesion . representative images , including : a plain radiograph ( figure 1 ) , 3d reconstructed computed tomography ( figue 2 ) and t1 coronal magnetic resonance imaging ( figure 3 ) indicated a bony excrescence from the inferior aspect of the left ischium measuring 1.7 x 1.1 cm . review of a previous ct scan from 2 years prior to the most recent study , demonstrated a stable lesion . plain x - ray : ap pelvis demonstrating pelvic digit arising from the left ischium 3d reconstructed computed tomography demonstrating the pelvic digit magnetic resonance imaging demonstrating a pelvic digit the above studies were suggestive of a pelvic digit . the patient s chief complaint was painful intercourse and she elected to proceed with a resection . pathology found no evidence of malignancy and the patient was discharged without pain and able to ambulate without support of a walker . the removed pelvic digit had two bony segments that formed a pseudoarticulartion or joint , visible in images a and b. follow up via a telephone communication indicated that her dyspareunia had resolved . literature reports have suggested various origins of the pelvic digit , including congenital formation , myositis ossificans , or traumatic avulsion.(1 - 3,5,6 ) in this case , the defining features were that it was well corticated with a pseudoarticulation between bony segments , resembling a digit . typically this would occur prior to the sixth week of fetal life in the mesynchymal stage.(6,8 ) in most reported cases the pelvic digit is an incidental finding on radiography . pandey et al . and maegele report the only other cases of symptomatic pelvic digits in a 35 and a 40 year old man , respectively.(6,9 ) these patients both experienced chronic hip pain , tenderness to palpation of the affected region and limited range of motion.(6,9 ) surgical excision was curative for chronic pain and increasing range of motion in both instances.(6,9 ) in summary , pelvic digits are typically incidental findings on imaging studies . however , in order to facilitate the diagnosis and treatment of pelvic conditions , physicians should be aware that this anomaly can be a source of pain and disability .

a pelvic digit is a rare congenital anomaly and often an incidental radiographic finding . here we present the first reported case of a 57-year - old caucasian female with a pelvic digit and a chief complaint of dyspareunia . radiographic studies and magnetic resonance imaging confirmed a stable bony excrescence from the inferior left ischium impinging on the pelvic floor . the patient underwent surgical removal of the pelvic digit without complications . accurate diagnosis of pelvic lesions is necessary to guide treatment .

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gastric cancer is the second most frequent cause of cancer - related death in the world and almost two - thirds of the cases occur in asian countries , especially china and japan . although current major therapies , including surgery and chemotherapy , have been widely used , the prognosis of gastric cancer is generally rather poor , with 5-year relative survival below 30% in most countries . however , the main cause of treatment failure in gastric cancer is the development of multidrug resistance to cytotoxic chemotherapies , which is at least in part related to the anti - apoptosis effect . it is well known that the resistance of cell death is one of the hallmarks of cancer cells . although the relationship between autophagy and cancer is still unclear , especially in the regulation of cancer development and progression , there has been much important progress in our understanding that autophagy may have important roles in the treatment of gastric cancer cells . autophagy is an evolutionarily conserved catabolic process by which damaged or long - lived cellular proteins and organelles are degraded . in the cancer cells it is still unclear if autophagy represents a survival mechanism or is involved in type ii programmed cell death ( pcd ) , which is termed autophagic cell death . autophagy is up - regulated when cells need to generate intracellular nutrients and energy , for example , during starvation , growth factor withdrawal , or high bioenergetic demands . moreover , basal autophagy can serve as an important homeostatic cellular recycling mechanism responsible for degrading unnecessary or dysfunctional cellular organelles and proteins in all living cells ; thus , autophagy can be viewed as a potent cytoprotective survival pathway in normal and cancer cells . recently , accumulating evidence has indicated that autophagy is particularly activated during metabolic stress such as nutrient depletion and hypoxia , and has a special homeostatic role mediating removal of old or dysfunctional proteins and organelles , and is particularly important for cell survival during conditions of metabolic stress . moreover , autophagy is the only mechanism for degrading large structures such as protein aggregates and damaged organelles . although autophagy has been induced in many different cancer cell lines , including gastric cancer cells using different agents such as chemotherapeutics , the role of autophagy in tumor cell death or survival is still unclear . autophagy has several adaptive roles in diverse human pathologies , including cancer and other diseases , and can act as a cytoprotective survival pathway . thus , under many conditions , autophagy is induced in response to many different forms of stress , including nutrient and growth factor deprivation and chemotherapeutics , and is utilized as a protective mechanism against cell death in the hostile environment . in fact , more and more results have suggested that autophagy can provide a survival advantage to tumors treated with chemotherapeutic agents . in human hepatocellular carcinoma and colorectal carcinoma cells , moreover , inhibition of autophagy by 3-methyladenine ( 3-ma ) can potentiate cisplatin - induced apoptosis in esophageal squamous cell carcinoma cells . in addition , many studies have revealed that inhibition of autophagy can augment cancer cell death through apoptosis , which indicates that autophagy may act as a protector in tumor cell survival . furthermore , other studies have proved that induction of autophagy can enhance tumor resistance in different tumor cell lines . hypoxia - induced autophagy can decrease hepatoma cell sensitization to chemotherapeutic agents that affect their apoptotic potential . in gastric cancer cells thus , results of many studies suggest that induction of autophagy can protect tumor cells against cancer treatment . previous studies have shown that inhibition of autophagy can potentiate the cell death induced by anticancer drugs in gastric cancer cells [ 1921 ] . therefore , we speculate that inhibition of autophagy may be a strategy for overcoming gastric cancer resistance to therapy . in recent years , the role of autophagy in cancer cells has been investigated extensively . although the impact of autophagy on tumor cells is still unclear and more studies are needed to prove the effects of autophagy in gastric cancer , recent research results suggest that autophagy may be a new target for combatting resistance of gastric cancer to therapy .

gastric cancer is the second most frequent cause of cancer - related death in the world and also causes much morbidity . the acquired resistance of cancer cells to drug reagents is becoming a major obstacle for successful cancer therapy . recently , many studies have revealed that macroautophagy ( here referred to as autophagy ) may be a prosurvival factor and protect the cancer cell from the development of drug - induced death . thus , we propose that autophagy may play an important role in the resistance of gastric cancer to therapy . although the exact role of autophagy in tumor cells is still unclear and further studies are needed to prove the role of autophagy in gastric cancer , recent research findings suggest a new direction in investigating the mechanism underlying resistance of gastric cancer to therapy .

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in the early 2000s , the grading of recommendations assessment , development and evaluation ( grade ) working group developed a framework in which the certainty in evidence was based on numerous factors and not solely on study design which challenges the pyramid concept.8 study design alone appears to be insufficient on its own as a surrogate for risk of bias . certain methodological limitations of a study , imprecision , inconsistency and indirectness , were factors independent from study design and can affect the quality of evidence derived from any study design . for example , a meta - analysis of rcts evaluating intensive glycaemic control in non - critically ill hospitalised patients showed a non - significant reduction in mortality ( relative risk of 0.95 ( 95% ci 0.72 to 1.25)9 ) . the quality of this evidence is rated down due to the methodological imitations of the trials and imprecision ( wide ci that includes substantial benefit and harm ) . hence , despite the fact of having five rcts , such evidence should not be rated high in any pyramid . the quality of evidence can also be rated up . for example , we are quite certain about the benefits of hip replacement in a patient with disabling hip osteoarthritis . although not tested in rcts , the quality of this evidence is rated up despite the study design ( non - randomised observational studies).10 therefore , the first modification to the pyramid is to change the straight lines separating study designs in the pyramid to wavy lines ( going up and down to reflect the grade approach of rating up and down based on the various domains of the quality of evidence ) . another challenge to the notion of having systematic reviews on the top of the evidence pyramid relates to the framework presented in the journal of the american medical association user 's guide on systematic reviews and meta - analysis . the guide presented a two - step approach in which the credibility of the process of a systematic review is evaluated first ( comprehensive literature search , rigorous study selection process , etc ) . if the systematic review was deemed sufficiently credible , then a second step takes place in which we evaluate the certainty in evidence based on the grade approach.11 in other words , a meta - analysis of well - conducted rcts at low risk of bias can not be equated with a meta - analysis of observational studies at higher risk of bias . for example , a meta - analysis of 112 surgical case series showed that in patients with thoracic aortic transection , the mortality rate was significantly lower in patients who underwent endovascular repair , followed by open repair and non - operative management ( 9% , 19% and 46% , respectively , p<0.01 ) . clearly , this meta - analysis should not be on top of the pyramid similar to a meta - analysis of rcts . after all , the evidence remains consistent of non - randomised studies and likely subject to numerous confounders . therefore , the second modification to the pyramid is to remove systematic reviews from the top of the pyramid and use them as a lens through which other types of studies should be seen ( ie , appraised and applied ) . the systematic review ( the process of selecting the studies ) and meta - analysis ( the statistical aggregation that produces a single effect size ) are tools to consume and apply the evidence by stakeholders . changing how systematic reviews and meta - analyses are perceived by stakeholders ( patients , clinicians and stakeholders ) has important implications . for example , the american heart association considers evidence derived from meta - analyses to have a level a ( ie , warrants the most confidence ) . a evidence could have been high , moderate , low or of very low quality.12 the quality of evidence drives the strength of recommendation , which is one of the last translational steps of research , most proximal to patient care . one of the limitations of all pyramids and depictions of evidence hierarchy relates to the underpinning of such schemas . the construct of internal validity may have varying definitions , or be understood differently among evidence consumers . a limitation of considering systematic review and meta - analyses as tools to consume evidence may undermine their role in new discovery ( eg , identifying a new side effect that was not demonstrated in individual studies13 ) . ebm teachers can compare it to the existing pyramids to explain how certainty in the evidence ( also called quality of evidence ) is evaluated . it can be used to teach how evidence - based practitioners can appraise and apply systematic reviews in practice , and to demonstrate the evolution in ebm thinking and the modern understanding of certainty in evidence .

a pyramid has expressed the idea of hierarchy of medical evidence for so long , that not all evidence is the same . systematic reviews and meta - analyses have been placed at the top of this pyramid for several good reasons . however , there are several counterarguments to this placement . we suggest another way of looking at the evidence - based medicine pyramid and explain how systematic reviews and meta - analyses are tools for consuming evidence that is , appraising , synthesising and applying evidence .

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extragonadal germ cell tumors ( eggcts ) have the same histological components as their gonadal counterparts , but a gonadal mass is not detectable by palpation or high - resolution ultrasonography ) here , we report a case of primary mediastinal seminoma with complete obstruction of the superior vena cava and no recurrence of the residual mass after intensive chemotherapy . his bilateral jugular veins were distended , and swollen lymph nodes were palpable in the right subclavicular region . a chest x - ray showed a mediastinal mass . computed tomography ( ct ) of the chest revealed a solid soft tissue mass ( 95 75 112 mm ) [ in diameter ] in the upper mediastinum , as well as a leftward displacement of the trachea and complete obstruction of the superior vena cava ( figure 1figure 1pretreatment ct shows a solid soft tissue mass ( 95 75 112 mm ) in the upper mediastinum , with leftward displacement of the trachea and complete obstruction of the superior vena cava . ) . based on the suspicion of a mediastinal tumor with lymph node metastasis , mediastinal radiotherapy and methylprednisolone were immediately started . biopsy of the right subclavicular lymph nodes revealed metastatic seminoma ( figure 2 figure 2biopsy specimen from a right subclavicular lymph node . well - defined tumor cells with large nuclei and clear nucleoli and a large clear reticulum are formed as map - like alveolar tumor cells . cobblestone growth can be seen with lymph node involvement surrounding the alveolar tissue . ) , and the patient was referred for chemotherapy . pretreatment ct shows a solid soft tissue mass ( 95 75 112 mm ) in the upper mediastinum , with leftward displacement of the trachea and complete obstruction of the superior vena cava . well - defined tumor cells with large nuclei and clear nucleoli and a large clear reticulum are formed as map - like alveolar tumor cells . lactate dehydrogenase , -human chorionic gonadotropin and alpha - fetoprotein were all in the normal ranges . ultrasound revealed a uniform , echogenic structure of the bilateral testicles , without any findings suggestive of malignancy . radiotherapy and methylprednisolone were discontinued , and systemic chemotherapy was simultaneously started with a combination of cisplatin , bleomycin and etoposide ( bep ) . since lung function test values deteriorated after one cycle of bep , bleomycin was excluded from subsequent chemotherapy , and the regimen continued with etoposide plus cisplatin ( ep ) . a partial response was observed after completing 3 cycles , but no further shrinkage was observed on subsequent examinations . salvage surgery was then considered for the residual mass because the superior vena cava was still completely obstructed by the tumor . although implantation of a prosthetic vessel was required , the procedure was not performed because it was considered to be a high risk surgery . instead , the patient received 2 courses of vinblastine , ifosfamide and cisplatin ( veip ) as salvage chemotherapy . on completion of the chemotherapy , the evaluable lesions were considered to represent a " stable disease " ( figure 3figure 3posttreatment ct shows less enhancement of a smaller soft tissue mass ( 30 18 36 mm ) . ) . as of december 2010 , there is no evidence of residual tumor growth , new masses or metastatic foci . the patient is being closely followed up on an outpatient basis and has been free of recurrence for 32 months after intensive treatment . posttreatment ct shows less enhancement of a smaller soft tissue mass ( 30 18 36 mm ) . our patient was first diagnosed as having an egct arising from the mediastinum when he presented with chronic cough and complete obstruction of the superior vena cava . since few patients with early germ cell tumors arising in the mediastinum have any symptoms , these tumors are often quite large by the time they are diagnosed and the mean maximum diameter of such tumors is reportedly 4.6 cm ) in 2008 , kesler et al . reported that 10 surgical deaths occurred among 158 patients who underwent additional resection of residual primary mediastinal nonseminomatous tumors ) like primary testicular seminoma , primary mediastinal seminoma has a good prognosis , and the rate of necrosis of the residual mass is as high as 92% when partial remission is obtained after chemotherapy )

a 20-year - old man was admitted to our hospital with persistent cough and dyspnea . he had bilateral distention of the jugular veins , and swollen lymph nodes were palpable in the right subclavicular region . plain x - ray and computed tomography ( ct ) of the chest showed a solid soft tissue mass in the upper mediastinum , with leftward displacement of the trachea and complete obstruction of the superior vena cava . mediastinal radiotherapy ( 1.8 gy / day ) and methylprednisolone ( 100 mg / day ) were started immediately . biopsy of the right subclavicular lymph nodes revealed metastatic seminoma . the patient was referred for chemotherapy , which was performed with a combination of cisplatin , bleomycin and etoposide ( bep ) . a partial response was observed after completion of 3 cycles of chemotherapy , but there was no further tumor shrinkage after additional salvage chemotherapy . the patient is being followed up on an outpatient basis and has been free of recurrence for 32 months after intensive treatment .

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pilomatricoma also known as benign calcifying epithelioma of malherbe is an uncommon slow growing benign adnexal skin tumor , which differentiates towards the hair matrix . , we report a case of pilomatricoma with bullous appearance in a young female which is rare , and also review the literature on bullous pilomatricoma . a 17-year - old girl presented with a solitary reddish semi - transparent blister over her right upper arm since 3 months . initially , the lesion started as a solid pin - head sized papule , which gradually progressed to form a semi - transparent blister with a hard nodule inside . no history of similar lesions in the past or in family members . on examination , single 2 cm sized erythematous semi - transparent bullae with a white nodule was seen on the medial aspect of the right upper arm [ figure 1a and b ] . on palpation , the bullae had a jelly like consistency and the nodule underneath was hard . on puncturing the lesion , it oozed a jelly like material . ( a and b ) 2 cm sized erythematous semi - transparent bullae with a white nodule inside photograph of a bouncy ball routine investigations were normal and excision biopsy was carried out [ figure 3 ] . histopathology revealed islands of basaloid cells with central abrupt keratinization and dilated lymphatics with dermal edema [ figures 4 and 5a ] . ghost cells ( shadow cells ) [ figure 5b ] , foreign body giant cell reaction [ figure 5c ] , and small foci of calcification were also seen [ figure 5d ] . with these findings , gross specimen of excised material histopathological features of excision biopsy showing islands of basaloid cells with central abrupt keratinization , shadow ( ghost ) cells , and dilated lymphatics with dermal edema ( h and e , 10 ) ( a ) basaloid cells undergoing abrupt keratinization ; ( b ) ghost cells / shadow cells ; ( c ) foreign body giant cell reaction ; ( d ) small foci of calcification ( h and e , 40 ) pilomatricoma is a benign tumor considered to be a hamartoma of the hair matrix composed of cells resembling those of the hair matrix , cortex , and inner root sheath . it makes up around 20% of all hair follicle - related tumors and is the commonest hair follicle tumor . majority of patients are under 20 years of age , and females are affected more often than males . it is usually a solitary , deep dermal or subcutaneous tumor 3 - 30 mm in diameter situated on the head , neck or upper extremities . clinical variants include , large ( giant ) , extruding or perforating lesions , ulcerative lesions , multiple eruptive cases , familial cases , superficial pilomatricoma presenting as a cutaneous horn and bullous pilomatricoma . association with myotonic dystrophy , gardner 's syndrome , turner 's syndrome , and rubinstein taybi syndrome have been reported with pilomatricoma . however , no such associations with bullous pilomatricoma has been reported . reports on bullous variant of pilomatricoma is sparse , and only 17 cases have been reported worldwide until date out of which only two cases are reported from india . bullous pilomatricoma has a predilection for occurring on the shoulder and upper arm regions , predominantly in females . it can also be found on the neck , trunk , eyelid , and scalp . the peak age of presentation is 10 - 20 years , and mostly of sizes 1 - 3 cm . usually presents as a solitary , flaccid , thick - walled red bullae with an underlying palpable hard nodule . our present case is consistent with these reports . since our case resembled a bouncy ball , we would like to coin this as the bouncy ball sign in bullous pilomatricoma . histopathological hallmarks of pilomatricoma are the tumor nests of basophilic cells and eosinophilic shadow cells . bullous variant in addition to these findings , show dilated lymphatic vessels , giant cell reaction , lymphoedema , disruption of collagen fibers , dilated blood vessels , fibrous capsule , calcification , nests of transitional cells , and necrosis . our case is consistent with these findings which showed islands of basaloid cells with central abrupt keratinization , shadow cells , dilated lymphatics with dermal edema , foreign body giant cell reaction and small foci of calcification . it could be due to mechanical irritation , or it could be a pseudoblister since the bullae - like spaces are filled with lymphatic fluid . another theory , suggests that the tumor cells or infiltrating inflammatory cells produce elastinolytic enzymes which disrupt the collagen fibers and destruct and dilate the lymphatic vessels , which lead to accumulation of lymph fluid in the dermis causing a bullae . however , the widely accepted theory is that obstruction of lymphatic vessels and congestion of lymphatic fluid caused by the growth of tumor nodule causes dilatation of lymphatic vessels , leakage of lymphatic fluid , and edema in the dermis surrounding the tumor resulting in the bullous appearance . malignant change ( pilomatricarcinoma ) is recorded in several cases , and appears to arise chiefly in large pilomatricomas that have been present for a long time . , dermatologists should be aware of this rare variant of pilomatricoma and excision biopsy is the norm for diagnosis and treatment of this condition .

pilomatricoma ( pilomatrixoma ) or calcifying epithelioma of malherbe , is a tumor with differentiation toward hair cells , particularly hair cortex cells . it frequently presents as a firm , deep - seated nodule that is covered by normal skin . bullous pilomatricoma is an unusual clinical variant . reports on bullous variant of pilomatricoma is sparse , and only 17 cases have been reported world - wide until date out of which only two cases are reported from india . we present a report of a 17-year - old female with a solitary reddish semi - transparent blister over her right upper arm since 3 months resembling a bouncy ball . histopathology revealed tumor nests of basophilic cells and eosinophilic shadow cells , which are consistent with pilomatricoma .

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in october 2004 , a 3-month - old kitten ( felis domesticus ) was adopted from the society of the prevention of cruelty to animals ( east london , eastern cape province , south africa ) and lived with its owner on a farm 23 km outside the city . it had been neutered and had been vaccinated at 10 months of age with an adjuvanted inactivated vaccine against rabies ( rabisin ; merial , lyon , france ) , but no subsequent vaccinations were given . the cat spent most of the day indoors , but went out at night and returned in the morning . it appeared dull and physically unbalanced and its pupils were dilated but it was not aggressive . the cat was humanely killed , and its brain was sent to the onderstepoort veterinary institute for rabies testing . on june 17 , 2005 , a 6-month - old puppy ( canis familiaris ) was brought by its owner to a veterinarian in the rural town of nkomazi ( mpumalanga province , south africa ) . after symptoms were treated , the dog was discharged , but it was brought back 11 days later because it was paralyzed , dehydrated , and had a fixed stare . the dog was humanely killed , and its brain was sent to the onderstepoort veterinary institute for rabies testing . direct immunofluorescent antibody test with an anti - rabies conjugate cross - reactive with african lyssaviruses showed numerous and strongly stained inclusion bodies in every field of impression smears of both brain samples . isolation of virus was attempted by suckling mouse brain passage and cell culture ( neuroblastoma cells ; diagnostic hybrids , athens , oh , usa ) ; both methods were successful for the cat sample . however , neither method yielded an isolate from the dog sample , despite a lyssavirus - specific reaction in the original brain sample by direct immunofluorescent antibody test . subsequently , antigenic characterization was performed with a panel of 16 monoclonal antibodies to the nucleocapsid protein of rabies virus ( canadian food inspection agency , nepean , ontario , canada ) . gt , genotype ; + , positive reactivity ; var , reactivity with some regional variants ; , negative reactivity . final confirmation of mokv in both case samples was obtained by reverse transcription pcr , nucleotide sequencing , and phylogenetic analysis as described ( 12 ) . phylogenetic analysis ( figure ) showed that the virus isolated from the cat sample ( designated mokv173/06 ) belonged to the same lineage of mokv isolates that were recovered from cats in the same region of south africa ( 12 ) . however , the virus detected in the dog sample ( designated mokv404/05 ) appeared to represent a different south african mokv lineage that was phylogenetically positioned between known south african and zimbabwean lineages . this mokv had nucleotide similarities of 88.1%90.4% and 85.3%88.5% with viruses from zimbabwe and south africa , respectively . phylogenetic tree based on 267 nt of partial nucleoprotein gene sequences of moloka virus ( mokv ) identified with the n1-n2 primer set as described ( 12 ) . the tree shows phylogenetic positions of 2 recently identified cases of mokv infection from south africa ( mokv173/06 from a cat and mokv404/05 from a dog ) ( in boldface ) relative to previously characterized mokv isolates from south africa ( sa ) and zimbabwe ( zim ) and lagos bat virus ( lbv ) as the outgroup . infections with mokv are rare ; only 23 isolates are known . during the past 2 decades , because these viruses are not exclusive to south africa ( 212 ) , lack of isolates from other regions of africa indicates a lack of active surveillance and limited diagnostic capabilities in many african laboratories . to our knowledge , the 2 cases of infection with mokv we report are the first in 8 years from south africa . clinical signs in the dog and cat , including general neurologic manifestations with a lack of aggression , are often signs that warrant submitting samples for rabies testing . whether these variations are caused by neutral genetic drift or reflect different epidemiologic features is not known . phylogenetically , divergence of these viruses into different lineages indicates active cycles and evolutionary changes that occur independently , but in close proximity ( a few hundred kilometers apart ) . although the epidemiology of mokv is incomplete , the case for a reservoir host(s ) among small terrestrial animals of limited range together with recent isolations of rabies - related lyssaviruses in a human ( 13 ) and wild animals ( 14,15 ) , these reports emphasize the endemicity of these lyssaviruses in south africa . public health implications of african rabies - related lyssaviruses should be recognized by laboratory workers , researchers , veterinarians , wildlife personnel , gamekeepers , and pet owners . a better understanding of the epidemiology of these viruses is vital and can only be achieved by improved surveillance and awareness .

we recently identified 2 mokola viruses from domestic mammals ( a dog and a cat ) in south africa . these cases occurred 8 years after the last reported case of infection with this virus . our findings emphasize the endemicity of rabies - related lyssaviruses in south africa and the need to better understand the epidemiology of mokola viruses .

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phyllodes tumor ( pt ) is a rare fibroepithelial neoplasm accounting for less than 1% of all breast tumors . benign pt ( bpt ) has hypercellular stromal fragments organized in leaflike patterns around benign epithelial / myoepithelial lined spaces . standardized cytologic diagnostic criteria of bpt includes increased stroma over epithelium , highly cellular stromal fragments , presence of phyllodes fragments ( i.e. , abundant leaflike stromal fragments ) , myxoid stroma , and numerous single bare nuclei of spindle fibroblastic type . diagnostic pitfalls of pt in fine - needle aspiration cytology ( fnac ) may be due to sampling error , high cellularity , ductal hyperplasia , paucity of stromal component , and occasional dissociation of epithelial cells . occasionally , only epithelial components of pt is represented in smears and may be misdiagnosed as epithelial neoplasm , particularly tubular adenoma and carcinoma . here , we present a case of bpt diagnosed by excisional biopsy , but its fnac features were misleading due to predominance of the epithelial component showing a tubular adenoma - like pattern . a 19-year - old female presented with an ill - defined mass in the left breast about ( 2.5 2 ) cm above the areola in the breast tissue . on fnac , smear was cellular comprising of the predominance of benign ductal epithelial cells showing prominent tubular adenoma - like arrangement [ figure 1 ] and resetting arrangement [ figure 2a ] . large branching sheets [ figure 2b ] and papillary clusters of ductal cells without a wavy or folded shape were seen as well . because of diversity in cytological findings , various differentials were thought such as tubular adenoma , adenosis , papilloma , and fibroadenoma . finally , it was cytologically reported as benign proliferative breast lesion with atypical / indeterminate features ( c3 category ) as per the cytologic categorization by the national coordinating committee for breast screening and the uk national breast screening program . as c3 category is a grey area in breast fnac diagnosis , further investigation such as excision biopsy duct epithelial cell clusters showing tubular adenoma - like pattern in fnac ( h&e stain , 200 ) ( a ) duct epithelial cells in sheets showing rosette - like arrangement in fnac ( h&e stain , 200 ) ( b ) large branching sheets of bland epithelial cells ( h&e stain , 200 ) ( c ) duct epithelial cells showing focal apocrine metaplasia ( h&e stain , 400 ) excision biopsy specimen grossly consisted of two grey white soft tissue masses measuring 3.5 cm 3 cm 1 cm and 2 cm 2 cm 1 cm . cut section showed grey white areas . on histology , a well - circumscribed biphasic neoplasm containing leaf - like , epithelial - lined papillary - like projections penetrating into cystic spaces with cellular stroma was seen . though , cytological features of pt have been well characterized , the cytologic diagnosis of pt remains difficult . this tumor is said to be underdiagnosed by the pathologists and undertreated by the surgeons . thus , the preoperative diagnosis of this tumor becomes very important to allow correct surgical planning and to avoid reoperation ( wide local excision with at least 1 cm margin is currently the treatment of choice for bpt ) . pt occurs in women aged 40 - 50 years , however , in asian countries pts may occur at a younger age ( average age , 25 - 30 years ) . cytologic distinction of bpt from fibroadenoma is possible by noting large epithelial clusters longer than 1 mm , with a wavy or folded shape , in contrast to the small or medium - sized clusters with tubular , blunt - branching , or monolayered contours of fibroadenoma . krishnamurthy et al . have observed that hypercellular stromal fragments with the presence of a significant proportion of long spindle nuclei ( > 30% ) is strongly indicative of pt , whereas the stromal cell nuclei in fibroadenoma tends to be short and oval and long spindle nuclei accounts for 10 - 30% . however , in our case , all the abovementioned features were absent , which made cytologic diagnosis difficult . standardized criteria for the diagnosis of bpt include at least two large stromal fragments , hypercellular fragments and moderate - to - large number of dissociated stromal cells . predominance of epithelial elements over stromal elements and monotonous population of cells with tubular adenoma - like and rosetting pattern as seen in this case can mimic epithelial neoplasm . large branching sheets of bland epithelial cells and focal apocrine metaplasia , seen here as well , closely mimics fibroadenoma . presence of papillary - like clusters and acinar pattern could be the reasons to consider papilloma and adenosis as other differential diagnosis . we conclude that if there is significant epithelial proliferation in bpt , a false diagnosis of epithelial neoplasm in fnac is possible and it is an important diagnostic pitfall . so , very careful strict criteria should be used such as advised repeat fnac , cell block preparation , biopsy , or correlation with clinical and radiologic findings to improve preoperative diagnosis of bpt . this will help in correct planning of surgical treatment , i.e. , wide excision with 1 cm margin .

benign phyllodes tumor ( bpt ) is a biphasic neoplasm composed of bland stromal and epithelial elements . cytologic diagnostic criteria of bpt , though documented in the literature , diagnostic pitfalls in fine - needle aspiration cytology ( fnac ) may occur due to sampling error , high cellularity , ductal hyperplasia , paucity of stromal component , and occasional dissociation of epithelial cells . here , we describe a case of bpt diagnosed by histology in a 19-year - old female , where fnac features were inconclusive due to paucity of stromal component , predominance of tubular adenoma - like epithelial component , and due to the presence of other overlapping features with fibroadenoma .

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we report a case , carbon dioxide ( co2 ) embolism a potentially devastating complication of laparoscopic surgery , during dissection phase and was successfully resuscitated . a 35-years - old female , weighing 42 kg was posted for transperitoneal laparoscopic boari 's ureteric reimplantation . her , physical examination and routine investigations were unremarkable . with routine monitoring , balanced general anesthesia was given . co2 pneumoperitoneum was created uneventfully using open insufflation technique and sustained with pressure of 14 mm hg . after 2 h , when the surgeon was dissecting the ureters , there was a sudden drop in etco2 ( 8 mm hg ) , tachycardia ( 130/min ) followed by multiple ventricular premature beats ( vpbs ) with blood pressure ( bp ) 110/72 mm of hg and sao2 - 98% . surgical bleeding and endotracheal tube blockage were ruled out , and gas embolism was suspected . injection lignocaine 80 mg intravenously was given for vpbs , and the regular rhythm was restored with the heart rate of 42/min . at this point , the sao2 decreased from 98% to 77% while the breath sounds were normal with no adventitious sounds . since there was no response to these measures , injection dopamine 20 ug / kg / min and nor - adrenaline 0.36 ug / kg / min were infused . multiorifice central venous catheter with its tip at the superior vena cava -right atrium ( svc - ra ) junction was inserted via right internal jugular vein but air could not be aspirated . after 20 min , resuscitative efforts were successful , patient had pulse rate of 120/min , bp 100/54 mm / hg , sao2 100% , etco2 30 mm / hg and ecg showed sinus rhythm with right ventricular strain pattern.at this time the cvp was found to be 10 mm of hg . two - dimension echocardiography ( 2-d echo ) showed no patent ductus arteriosus or any other congenital defects . she was shifted to intensive care unit with dopamine 5 ug / kg / min . which was tapered and stopped after h. the patient did not receive hyperbaric oxygen as we did not have the facility . co2 embolism can occur either during peritoneal insufflationor during the surgical dissection . in this case , possible causes of sudden cardiovascular collapse like hypovolemia , hemorrhage , vaso - vagal reflex , pneumothorax and endotracheal tube blockage were ruled out before considering gas embolism the adhesions caused by previous surgery might have led to vascular injury during dissection and the operating site was above the level of the heart ( trendelenburg position ) creating a pressure gradient thus the open venous channels , at lower pressure were open to gaseous medium at a higher pressure leading to gas embolism . either , slow infusion of air ( 0.01 - 2.00 ml / kg / min ) or bolus of gas ( 25 - 200 ml or 1 - 13 ml / kg ) , creates a gas paradoxical air embolism was ruled out by a 2-d echo that showed no intra - cardiac channels . any kind of pulmonary embolism leads to sudden deterioration of the hemodynamic status associated with decreased etco2 levels . since co2 is a highly soluble gas ( 54 ml / dl ) , prompt recovery of the vital signs is usual . aspiration of gas through central venous catheter is the definitive means of treating gas emboli . in our case , failure to aspirate the gas may suggest that it might have been trapped in the pulmonary vasculature . tee is the gold standard for detection of pulmonary air embolism , however , it is not indicated routinely for intra - operative monitoring . sudden decrease in etco2 is an early sensitive but nonspecific sign of venous air embolismprecordial stethoscope enhances specificity of etco2 and mean pulmonary artery pressure values . immediate treatment of gas embolism requires deflation of pneumoperitonium , placing the patient in durant 's position , hyperventilation and administration of 100% oxygen . aggressive cardiopulmonary resuscitation should be continued till the acute effects of the embolism abate and one should maintain positive circulating volume to prevent further entrainment of the gas . thus , in laparoscopic surgeries early detection of gas embolism with prompt resuscitation can result in a favorable post - operative outcome .

carbon dioxide ( co2 ) embolism is a rare but potentially fatal complication of laparoscopic surgery . we report a case of presumed co2 embolism in a 35-year - old female during laparoscopic ureteric reconstructive surgery . after 2 h of operating time , a sudden decrease in end - tidal carbon dioxide and deterioration of hemodynamic status followed by cardiac arrest with pulseless electrical activity suggested gas embolism . immediate cardiopulmonary resuscitation and inotropic support resulted in successful outcome . thus , early recognition of the complication and prompt treatment can avoid catastrophy .

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we report the first french case of r. aeria ie complicated by brain haemorrhage and femoral mycotic aneurysms , in an immunocompetent patient . a 57-year - old man born in nepal was hospitalized in january 2016 for fever reaching 39.4c , chills , diarrhoea and headache . he had a previous history , in 2008 , of right sub - thalamic ischaemic stroke and severe mitral insufficiency without ventricular dysfunction for dystrophic mitral valve . he did not have recent dental care and had no history of intravenous drug injections . at admission the patient presented with an already known 4/6 meso - systolic rough mitral murmur without cardiac failure and a painful erythema of the right hand ( fig . two aerobically incubated blood cultures performed at admission were positive with gram - positive branching filamentous bacilli ( fig . 1b , c ) within 41 and 86 h , as were the seven other blood culture sets . colonies were identified as r. aeria using matrix - assisted laser desorption - ionization time - of - flight mass spectrometry ( see fig . trans - oesophageal echocardiography revealed mitral ie with several nearby vegetations of the ring base , flail p1 without heart dysfunction or abscess ( fig . pre - operative screening for systemic embolism showed a left frontal subarachnoid haemorrhage on brain magnetic resonance imaging and a hypermetabolic focus in the femoral artery compatible with a mycotic aneurysm on positron emission tomodensitometry ( fig . empiric antibiotherapy was introduced according to european guidelines with intravenous amoxicillin 2 g every 4 h and gentamicin 3 mg / kg once a day . surgical mitral replacement by bio - prosthesis with annular reconstruction was performed according to the risk of cerebral embolism and cardiac abscess at day 10 after initiation of antibiotics . blood culture negativity was obtained at day 3 after antibiotics initiation and valvular culture was negative . 16s rrna gene sequence analysis was performed on the mitral sample and confirmed the identification of r. aeria ( genbank accession sequence kx270977 ) with a maximal identity of 100% for r. aeria type strain a1 - 17b ( genbank accession number ab071952 ) . antibiotic combination was maintained for 2 weeks , then amoxicillin alone for a further 4 weeks . subarachnoid haemorrhage regressed and trans - oesophageal echocardiography showed a good functioning of the prosthesis and the absence of added elements . initially r. aeria was known as rothia dentocariosa genomovar ii and could be mistaken for nocardia spp . except for its antibiotic sensitivity . infective endocardites due to r. aeria ( n = 7 ) and r. dentocariosa ( n = 25 ) , are reported to be associated with central nervous system involvement in 13 of the 32 cases ( 40% ) published , , . antibiotic susceptibility of the r. aeria strains isolated in all case reports showed sensitivity for ampicillin and gentamicin . we report the first infective ie due to r. aeria described in france and confirm that r. aeria ie is serious and associated with mycotic aneurysms and central nervous system involvement . fast and aggressive management with an antibiotic combination including penicillin for 46 weeks , and valve replacement when necessary , is required and could limit the occurrence of complications and death .

rothia aeria is a rothia species from the micrococcaceae family . we report here the first french r. aeria endocarditis complicated by brain haemorrhage and femoral mycotic aneurysms . altogether , severity and antimicrobial susceptibility should make us consider the management of r. aeria endocarditis as staphylococcus aureus methicillin - susceptible endocarditis .

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most patients with hodgkin 's disease and spinal epidural involvement either present with concurrent neurological and nodal disease or develop neurological disease after being diagnosed with hodgkin 's disease . a case of a 30-year - old male patient with primary thoracic epidural lymphoma who presented with back pain is presented in this paper . the severity of pain was associated with the inability to perform the activities of daily living . the patient did not have any lymphoma - related b - type symptoms , including body weight loss , fever and sweat at night . a magnetic resonance imaging ( mri ) scan of the thoracic spine demonstrated an epidural tumor at the t911 level ( figs 13 ) . histological examination revealed the polymorphous cellular infiltration by histiocytes , large mononuclear cells and lacunar reed sternberg cells with folded multi - lobed nuclei and small nucleoli ( fig . 4 ) . immunohistochemical staining was positive for cd15 and cd30 and negative for cd3 , cd20 , cd79a or cd45ro . these features were most frequently observed in the mixed cellularity type of hodgkin 's lymphoma . the results of all other examinations ( f-18 fluorodeoxyglucose positron emission tomography ( f-18 fdg pet / ct ) , bone marrow biopsy and computed tomography ( ct ) of the chest , abdomen and pelvis ) were negative for an occult disease . six courses of chemotheraphy containing abvd regimen ( adriamycin , bleomycin , vinblastine and dacarbazine ) were given to the patient . postoperative mri scan did not reveal any evidence of hodgkin 's disease ( fig . 5 ) , f-18 fdg pet / ct , ct of the chest , abdomen and pelvis were obtained in 24 months and did not reveal any evidence of hodgkin 's disease . figure 1:t2 weighted mri revealed a mass at the t9 - 11 level . figure 2:t1 weighted mri revealed a mass at the t9 - 11 level . figure 3:axial t1 weighted mri revealed at the epidural space . figure 4:histological examination revealed mixed cellularity type of hodgkin 's lymphoma . figure 5:postoperative mri scan did not reveal any evidence of hodgkin 's disease . t2 weighted mri revealed a mass at the t9 - 11 level . patients with hodgkin 's disease develop spinal cord compression caused by epidural hodgkin 's lymphoma and usually observed in the presence of an advanced disease [ 1 , 2 ] . there are six case reports in the literature that describe patients with primary spinal epidural hodgkin 's lymphoma [ 16 ] ( table 1 ) . samadian et al . reported a case of primary and isolated spinal epidural hodgkin 's lymphoma at l1l3 level . al - khayat et al . reported a hodgkin 's lymphoma case with epidural involvement at c7t1 level . reported a case with primary extranodal hodgkin 's disease who underwent decompressive surgery accompanied with stabilization and radiotheraphy . reported cases with primary spinal epidural hodgkin 's lymphoma ( s : surgery , rt : radiotheraphy , ct : chemotheraphy e : epidural , v : vertebral , p : paraspinal ) moridaira et al . rao et al . published a case with primary spinal epidural hodgkin 's lymphoma . our case is apparently the seventh case to be diagnosed with hodgkin 's disease who presented with spinal cord compression due to epidural space without lymphoma elsewhere . the abnormal mri marrow signal of the t9 and t10 vertebral bodies can be seen in fig . maybe the tumor in fact originated within the abnormal t9 or t10 bone marrow and spread to the epidural space via the epidural venous plexus . surgery is the first therapeutic approach in malignancies compressing the spinal cord . because hodgkin 's lymphoma is a very chemosensitive and radiosensitive tumor , the indications for surgery were reduced and limited to laminectomy or even biopsy only , leaving the major role to chemotheraphy and radiotheraphy . the combination of chemotheraphy and involved - field radiotheraphy is the most common treatment strategy ; two to four cycles of abvd are considered as the international gold standard for early - stage hodgkin 's lymphoma in combination with 2030 gy of involved - field radiotheraphy [ 7 , 8 ] . we chose the first therapeutic approach for this patient who underwent gross total resection of the tumor , because the tumor type was unknown at the time of initial presentation . the present case demonstrated that physicians should include primary spinal epidural hodgkin 's lymphoma in the differential diagnosis of spinal tumors . treatment of hodgkin 's lymphoma will almost always include in the acute phase a form of emergency decompressive surgery , with or without resection , followed by chemotheraphy and/or radiotheraphy .

primary spinal epidural hodgkin 's lymphoma is very rare . we will discuss the clinical features and treatment of primary spinal epidural hodgkin 's lymphoma . in this paper , a 30-year - old male patient who presented with spinal epidural tumor at the t911 level is reported . subtotal resection of the tumor was performed and the histological examination of the tumor specimen revealed hodgkin 's lymphoma . all other examinations were negative for an occult disease . six courses of chemotheraphy containing adriamycin , bleomycin , vinblastine and dacarbazine were given to the patient . surgery is the first therapeutic approach in malignancies compressing the spinal cord . hodgkin 's lymphoma is a very chemo- and radio - sensitive tumor . the indications for surgery were reduced and limited to laminectomy or even biopsy only , leaving the major role to chemo- and radiotheraphy .

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