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leiomyoma is a benign tumor , which is made up of smooth muscle cells and located mostly in uterus , small bowel , and esophagus . herein , a prostatic leiomyoma that was pathologically reported after a robot - assisted radical prostatectomy ( rarp ) procedure is presented . a 70-year - old male patient with a serum prostate specific antigen value of 9.8 ng / ml underwent a transrectal ultrasound ( trus ) guided prostate biopsy . pathology revealed prostatic adenocarcinoma with 3 + 3 gleason score in 1 core on the left side . the patient had a history of irritable bowel syndrome and had bilateral inguinal herniorrhaphy operation performed 8 years ago . a transperitoneal rarp procedure with bilateral pelvic lymph node dissection was performed ( by dr . briefly , an incision was made on the anterior peritoneal covering of the douglas ' pouch , 1 cm proximal to its reflection on the rectum . seminal vesicles ( svs ) and vasa deferentia were dissected . at this stage , a 3 3 cm sized posterior mass lesion protruding from the prostate between svs was identified and dissected ( fig . figure 2 shows the removed specimen with a mass lesion protruding from the prostate located between svs . postoperative follow - up was uneventful , abdominal drain was removed at the postoperative second day , and patient was discharged on the third day . transurethral catheter was removed on postoperative day-10 followed by obtaining a cystography that demonstrated no leakage . pathology was reported as prostate adenocarcinoma , gleason score 3 + 3 , tumor size of 5 4 3 mm , left apex , and single focus with clear surgical margins . posteriorly located mass pathology was reported as a leiomyoma with a size of 3.5 3 2.8 cm . prostate had a weight of 210 g. microscopy of this mass lesion revealed a fascicular pattern of smooth muscle bundles separated by well - vascularized connective tissue ( fig . smooth muscle cells were elongated with eosinophilic or occasional fibrillar cytoplasm and distinct cell membranes . one to 2 mitotic figures per 10 high power fields in most mitotically active area were observed , and there was no significant atypia ( fig . also a single focus of prostate adenocarcinoma with gleason score 3 + 3 , size of 5 4 3 mm , located on left apex , with clear surgical margins was reported . a mass lesion , made up of smooth muscle bundles , is well demarcated from prostate tissue on the left ( h&e 4 ) . smooth muscle cells with bland cytology form fascicules ( h&e 40 ) . immunohistochemically smooth muscle actin is positive ( inset 40 ) . at postoperative ninth - month follow - up , patient is fully urinary continent with no safety pad usage . he is able to have penile erection for sexual intercourse with use of phosphodiesterase type 5 inhibitors . although pure prostatic leiomyoma is rarely seen , it was reported initially in 1876 in the autopsy material by lebel et al . in 1951 , kaufman and berneike defined prostatic leiomyomas . in 2016 , kristensen et al . stated that prostatic leiomyomas were reported in < 100 cases since it was defined . in addition , the origin of prostatic leiomyoma may reveal as wastes of mllerian duct . however , a certain mechanism of formation of prostatic leiomyoma is still not clearly presented . robotic surgery for the surgical management of a leiomyoma was previously performed by aoun et al . however , in our case the whole prostate with the posteriorly located leiomyoma was removed with the rarp procedure . the console surgeon in our case was challenged with the identification of a large mass lesion located between the svs as this area has already a limited space . therefore , it was surgically not difficult to dissect and isolate this mass lesion . however , the presence of this mass lesion made it challenging to open the denonvilliers ' fascia due to its close proximity with rectum . at this stage , intra - abdominal pressure was elevated as much as 18 mmhg temporarily to better see the area and a 4 close up magnification was used with the da vinci xi surgical robot . fourth arm of the robot holding a prograsp forceps was effectively used to lift up the prostate by holding from the svs in an attempt to make the console surgeon to see the area below the mass lesion . it is important to keep in mind that this maneuver might lead to tearing off the svs if too much force is applied as there is no tactile sensation in robotic surgery . a further trick that might also be applied could be using a 30 up lens to better see the area below the mass lesion . leiomyoma is a benign tumor and has excellent prognosis when complete resection is applied and atypia is not detected . on our case , vandoros et al . stated that negative surgical margins and absence of metastatic disease at presentation were the only factors predictive of long - term survival . therefore , prostatic leiomyosarcomas should also be kept in mind in the differential diagnosis . in conclusion , prostatic leiomyomas that are benign mesenchymal smooth muscle tumors might present as a posteriorly located mass lesion between svs that could challenge the surgeon during surgery , which should be kept in mind .

abstractbackground : prostatic leiomyoma is a benign and rare condition of the prostate . robotic surgery is increasingly being applied in the surgical management of prostate cancer.case presentation : herein , a mass lesion that was located in the posterior part of the prostate between seminal vesicles that was identified during robotic surgery is presented . this lesion further challenged the console surgeon during performing a robotic radical prostatectomy procedure for a 200 g large prostate with prostate cancer.conclusion : prostatic leiomyomas that are benign mesenchymal smooth muscle tumors might present as a posteriorly located mass lesion between seminal vesicles that could challenge the surgeon during surgery , which should be kept in mind .

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as a professor in a clinical department , i am privileged to work with many clinician - investigator trainees . recently , a new clinical research fellow told me that he had been reading many papers in order to decide which research project he should take . the more he reads , the more confused he feels . in fact , this challenge is not only to new fellows , but also to experienced researchers . in this issue of critical care , dr li and dr quinn and their colleagues published a research article exploring the molecular mechanisms of ventilator - induced lung injury ( vili ) . i would like to use this interesting article as an example , to lead readers who are not experts in this field through a translational process . mechanical force - induced signal transduction ( mechano - transduction ) is responsible for many physiological processes in lung development , in maintaining lung functions , and in pathological conditions related to lung diseases , such as asthma , chronic obstructive pulmonary disease ( copd ) , and acute respiratory distress syndrome ( ards ) , especially related to vili . however , very much like the routes in a city , both " good boys " and " bad boys " drive on the same streets . neutrophil recruitment and activation is an important mechanism for lung tissue injury , which is mediated by a group of small molecules , namely chemokines , especially a subgroup of c - x - c chemokines . interleukin-8 ( il-8 ) is the best example , which has been shown to be up - regulated by mechanical forces in human lung cells . rodents do not have the il-8 gene , but produce macrophage inflammatory protein-2 ( mip-2 ) and other c - x - c chemokines . they further questioned that neutrophil migration is mediated by a signal pathway activated by akt ( also called protein kinase b ) . they also used a chemical inhibitor to prevent the activation of akt in mice , prior to their exposure to high volume ventilation and/or hyperoxia . however , it is worth mentioning that the akt pathway is also critically important for proliferation , survival and migration of cell types other than neutrophiles . based on their recent studies , these researchers suspected that endothelial nitric oxide synthase ( enos ) activation is also part of the mechanisms responsible for vili . they demonstrated increased phosphorylation of enos and also demonstrated that nitric oxide synthase ( nos ) inhibitor could attenuate vili . increased nos expression and/or activity have been shown in multiple lung injury models and clinical samples . the outcome of no related clinical studies , however , is controversial , which warns us for further investigation . as a clinician you may ask why 30 ml / kg of tidal volume was used in this study and you may note that oxygen was used for ventilation . first of all , as experimental biologists , we always try to create a condition that can give definite answers . for example , after serum starvation , add a growth factor into the culture medium to initiate a signal transduction , or start mechanical stretch on statically cultured cells . these protocols help us to reveal the potential of a biological stimulus on a particular biological process . this strategy has also been adapted to animal studies . on the other hand , this may also explain why many experimental findings did not translate to good clinical practices . as a bench scientist , one should try to simulate clinical conditions as much as possible . recently , clinically relevant models have been emphasized . after going through this interesting paper critically , what have we learnt ? first , good literature review may lead to proposal of a testable hypothesis in vili . secondly , the mechanical force - induced signal transduction by injurious ventilation ( high tidal volume and high oxygen tension ) could activate pathways that are important for normal functions . last but not the least , awareness of the significance and limitation of experimental data are crucial for our knowledge translation . ards = acute respiratory distress syndrome ; copd = chronic obstructive pulmonary disease ; enos = endothelial nitric oxide synthase ; il-8 = interleukin-8 ; mip-2 = macrophage inflammatory protein-2 ; no = nitric oxide ; nos = nitric oxide synthase ; vili = ventilator - induced lung injury .

mechanotransduction holds the underlying mechanisms of ventilator - induced lung injury . research on this subject , however , could be difficult for clinicians , especially when results are controversial . a recent study by li and co - workers is used as an example , to explain how to critically read literatures related to basic science and how to understand the limitation of experimental studies .

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iridodialysis commonly occurs secondary to blunt ocular trauma,1 penetrating ocular trauma , and intraocular surgical procedures . in the cases of small iridodialysis the upper eyelid covers iridodialysis superiorly and prevents symptoms . however , temporal iridodialysis is usually symptomatic . in addition to visual problems such as diplopia , glare , and photophobia , cosmetic problems such as polycoria and ectopic pupil might occur due to large iridodialysis . a number of surgical techniques have been described for the repair of iridodialysis.245678 we describe a novel cobbler 's technique for repairing iridodialysis in the right eye of an 18-year - old patient . following peribulbar anesthesia , a fornix - based localized conjunctival peritomy ( 611 oclock ) was performed in the right eye of a patient with traumatic iridodialysis extending from 7 oclock to 10 oclock position in the inferotemporal quadrant [ figure 1 ] . a partial thickness scleral tunnel was created 1.5 mm from the limbus along the extent of the iridodialysis . a limbal paracentesis was created with a stiletto knife at the 2 oclock position , and intracameral pilocarpine was injected into the anterior chamber to place the iris tissue on the maximal stretch . the 26-gauge needle was passed through the paracentesis and the 10 oclock end of the scleral groove engaging the root of the iris . the needle was withdrawn into the anterior chamber and taken out at the 9.30 oclock position engaging the root of the iris again . the prolene suture was pulled out forming a loop through which the free end of the suture was passed to lock the loop . this step was repeated multiple times until multiple loops laid over the scleral bed [ figure 2 ] . these loops were then tied [ figure 3 ] and the conjuctival peritomy was closed using 8 - 0 vicryl sutures . preoperative photograph showing a corneal scar inferiorly and a large iridodialysis from 7 oclock to 10 oclock position illustration of passage of the 10 - 0 polypropylene suture from iris to sclera with multiple suture loops lying over the scleral bed illustration of suture tied at 7 oclock position first postoperative day photograph of the same eye after iridodialysis repair postoperative photograph 3 weeks following surgery functional symptoms , such as glare and monocular diplopia , result from the polycoria of a pseudo - pupil created by the iridodialysis . typically , these complaints are most commonly seen when iridodialysis is located in the nasal , temporal , or inferior quadrants , as was seen in our patient . cosmetic deformities associated with iridodialysis can affect self - esteem adversely and thus have a major psychosocial impact on the patient.910 various methods for surgical repair of iridodialysis2345678 have been described in literature . most of these procedures require more surgical maneuvers and anterior chamber is often not stable while repairing large iridodialysis . the advantages of cobbler 's technique for repairing iridodialysis as described above include : ( 1 ) it is performed through a small paracentesis wound ; ( 2 ) the anterior chamber remains stable throughout ; ( 3 ) multiple sutures can be passed without withdrawing the needle from anterior chamber ; ( 4 ) large dialysis can be repaired easily ; ( 5 ) the shape of the iris can be controlled ; ( 6 ) only one suture knot is required at the end of the incision which can be easily be buried within the sclera groove minimizing the likelihood of late suture erosion . our novel cobbler 's technique for iridodialysis repair allows a maximally functional and cosmetic result . this technique was named cobbler 's technique since it bears great similarity to the way a cobbler repairs shoes .

we describe a novel cobbler 's technique for iridodialysis repair in the right eye of a patient aged 18 years , with a traumatic iridodialysis secondary to open globe injury with an iron rod . our technique is simple with easy surgical maneuvers , that is , effective for repairing iridodialysis . the cobbler 's technique allows a maximally functional and cosmetic result for iridodialysis .

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bidirectional ventricular tachycardia ( bvt ) is defined as a tachycardia showing beat - to - beat alternation in the qrs axis . the rate is typically between 140 and 180 bpm , with a frontal plane axis varying between 20 and 110. the most common causes of bvt include catecholaminergic polymorphic ventricular tachycardia and cardiac glycoside toxicity . other previously described etiologies include myocarditis , long qt syndrome type 7 , congenital cardiomyopathies , cardiac tumors , and acute cardiac allograft rejection . cardiac sarcoidosis is characterized by myocardial inflammation and interstitial fibrosis that can lead to slowed conduction and macro re - entrant arrhythmias . we report a case of bvt in a patient with cardiac sarcoidosis and briefly discuss the proposed mechanisms underlying bvt . a 73-year - old man with history of chronic pulmonary sarcoidosis was seen for an annual checkup , during which ventricular bigeminy was identified on a 12-lead electrocardiogram . subsequent holter monitor assessment showed multiple premature ventricular beats and several short runs of non - sustained ventricular tachycardia ( vt ) , with two different qrs morphologies ( fig . 1 ) . a cardiac magnetic resonance tomography with delayed gadolinium showed a curvilinear region of patchy mid - myocardial enhancement within the inferolateral left ventricular myocardium near the base , consistent with cardiac sarcoidosis ( fig . 2 ) . the left and right ventricular ejection fractions were 47% and 37% , respectively . a nuclear myocardial perfusion study using single - photon emission computed tomography showed no myocardial perfusion defects on stress or rest imaging , ruling out ischemia . a fasting 18-fluorodeoxyglucose positron emission tomography ( pet ) demonstrated increased uptake in the same area of the myocardium that had shown late gadolinium enhancement , consistent with active cardiac sarcoid ( fig . the patient was elected to have an implantable cardioverter defibrillator ( icd ) placed for prevention of sudden cardiac death . he had not experienced any vt episodes during the one - year follow - up . one of the proposed mechanisms of bvt include elevated intracellular calcium , causing delay after depolarization in anatomically separate parts of the conducting system . proposed that two separate foci , with different rate thresholds for delayed after depolarization induced ventricular bigeminy , were present in a rabbit model . this would effectively double the heart rate , increasing the overall ventricular rate above the second threshold . once this had developed , the two competing sites would simply alternate on a beat - to - beat basis . this is likely the mechanism underlying bvt observed with digitalis toxicity and catecholaminergic polymorphic vt . the other proposed mechanisms for bvt include an alternating bundle branch block related to bifocal automaticity and inscribed in opposite directions , or scar - mediated reentry around a circuit with two alternating exit sites . described a mechanism including retrograde conduction over the mid septal fascicular pathway , with alternating block in the left anterior or posterior fascicles , to explain polymorphic fascicular vt patterns . scarring is typically patchy , with a predilection for the basal septum , anterior wall , and perivalvular regions of the left ventricle . it may also be confluent , affecting the right ventricular epicardium or endocardium . in sarcoidosis , it is plausible that multiform or bidirectional premature ventricular contractions ( pvcs ) are due to multiple exits from the areas of inflammation and/or scarring . conduction disturbances in cardiac sarcoidosis are not uncommon , and often affect the his - purkinje system . in our case , the patient had an intraventricular conduction delay at baseline , with prolonged qrs complexes at relatively low atrial rates ( fig . the majority of the retrospective data suggest that immunosuppression reduces the burden of arrhythmias , especially in the early phases of the disease . previous case series have reported various success rates with vt ablation in patients with cardiac sarcoidosis , likely due to the small number of patients in each series , with varying degrees of disease burden . the most common circuit for vt in one report was reentry in the peritricuspid area , which can be safely ablated . in another study , abolishing all inducible tachycardias was not always feasible because of septal intramural circuits , extensive right ventricular scarring , or sites of origin in close proximity to the left anterior descending , the ramus intermedius arteries , or the para - hisian region , which prohibit safe ablation . in the current case , it is likely that the presence of a septal focus leads to alternate exits into the right or left ventricle which shows the observed electrocardiogram pattern . although the septal involvement was not visible by imaging until a year after diagnosis , it might have been present initially , but was microscopic in nature . this is consistent with previous autopsy studies that have shown a heterogeneous distribution of sarcoid granulomas in the myocardium . the recent expert consensus document is an excellent resource for management and risk stratification for cardiac sarcoidosis patients . icd implantation for primary prevention is commonly performed due to the high burden of vt events ( estimated incidence rate of 15% per year ) in patients with cardiac sarcoidosis . in the current case , icd implantation was recommended due to the high burden of nonsustained vt episodes , left and right ventricular dysfunction , and the presence of fibrosis and active inflammation by imaging studies .

a 73-year - old man with history of pulmonary sarcoidosis was found to have runs of non - sustained bidirectional ventricular tachycardia ( bvt ) with two different qrs morphologies on a holter monitor . cardiac magnetic resonance delayed gadolinium imaging revealed a region of patchy mid - myocardial enhancement within the left ventricular basal inferolateral myocardium . an 18-fluorodeoxyglucose positron emission tomography ( fdg - pet ) showed increased uptake in the same area , consistent with active sarcoid , with no septal involvement . follow - up fdg - pet one year later showed disease progression with new septal involvement . cardiac sarcoidosis , characterized by myocardial inflammation and interstitial fibrosis that can lead to conduction system disturbance and macro re - entrant arrhythmias , should be considered in differential diagnosis of bvt . bvt may indicate septal involvement with sarcoidosis before the lesions are large enough to be detected radiologically .

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a 45year old woman was admitted to our hospital and surgery was planned for right staghorn calculus ( figure 1 ) . ultrasound showed multiple calculi in the right kidney ; 38 mm in the pelvis , 21 mm in the lower pole and 16 mm in the upper pole with moderate hydronephrosis . intravenous urography showed right renal staghorn calculus with delayed excretion suggestive of impaired right renal function . ray showing the burden of calculi in the right kidney . under general anesthesia , initial ureteric the procedure was carried out with the patient in prone position using a c arm and bull 's eye technique . lower pole puncture was done and the stones in the lower calyx , middle calyx and pelvis were cleared . an upper pole puncture was done under c arm guidance and bile was observed gushing out of the needle when the stiletto was removed . a 20 fr foley catheter was kept as a percutaneous nephrostomy tube and the patient was put on antibiotics according to urine culture and sensitivity along with metronidazole . in the immediate post operative period , the patient was closely monitored with parameters such as pulse rate , blood pressure , abdominal girth monitoring , water balance and nasogastric tube aspirate . the patient had two episodes of vomiting in the immediate post operative period and mild distension of the abdomen . an ultrasound was performed twenty four hours after surgery and revealed minimal collection in the gall bladder fossa ( < 10 ml ) with pelvic collection ( < 50 ml ) . a 72 hour scan was done which showed resolution of the gall bladder fossa collection . the patient had no signs of peritonitis and responded well to conservative line of management . she was discharged home on post operative day five and was followed up after two weeks with renal function test and liver function tests which were within normal limits . according to clavien dindo grading system for surgical complications this case fits into grade 2 . percutaneous nephrolithotomy is the treatment of choice for large ( > 2 cm ) renal staghorn calculi [ 1 , 2 ] . it constitutes a small number of all complicated visceral injuries during pcnl . till date , only six cases have been documented in literature . other organ injuries such as spleen , liver and colon have been documented , with gall bladder injuries being the least common . a well distended gall bladder is in close proximity to the right kidney and medial right sided percutaneous renal access may increase the risk of gallbladder injury . it is significant to bear in mind that gall bladder injury is not a common complication but is still commonly encountered in thin individuals . most of the cases in the literature have undergone immediate cholecystectomy . in our case , pcnl was not abandoned and the patient did not undergo cholecystectomy ; our case was instead managed conservatively . in the post operative period , close monitoring is required , both clinical and by means of ultrasound . if there is deterioration in the clinical scenario , then immediate cholecystectomy has to be done . in our case , the leak subsided and spontaneous closure of perforation occurred , most probably due to the use of a two piece diamond tip needle , which is supposed to be less traumatic as compared to other conventional needles .

percutaneous nephrolithotomy ( pcnl ) has been an excellent option for the management of kidney stones . there have been many complications in regards to solid organ injury during pcnl . here we discuss an interesting case of 45-year - old woman , who underwent pcnl for right renal staghorn calculus , and had an accidental puncture of the gall bladder . post operatively , the patient was conservatively managed and recovered well . a small number of cases has been reported until now in literature .

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nephrogenic adenoma is a rare lesion of the urinary bladder that may arise and induced by many inflammatory insults such as recurrent infections , recurrent renal stone , intravesical therapy , bladder diverticula , renal transplantation , foreign bodies , chemical agents , radiation therapy , and other chronic irritative factors . in 1954 , mostofi reported that the urinary bladder epithelium had the ability to transform into several morphologic types under appropriate stimulation and suggested that squamous and glandular metaplaisa of the urothelium is seen frequently in association with chronic infection . nephrogenic adenoma ( nephrogenic metaplasia ) shows a male predominance with a male to female ratio of 2:1 , and occurs over a wide age range ( 4 - 81 years ) . although most common in adults , approximately 10% of nephrogenic adenomas have been observed in children . in 1950 friedman and kuhlenbeck described eight such cases as nephrogenic adenoma resembling aberrant tubules of the kidney . the origin of the tumor is uncertain , and many believed that it might originate from embryonic mesonephroid tissue . the majority of reports indicate that this type of lesion is due to urothelial injury as a result of previous surgery or long - term inflammation . immunosuppressive therapy as in renal transplantation and intravesical drug ( bcg ) infusion are suspected causes in nephrogenic adenoma . the clinical and cystoscopic characteristics of nephrogenic adenoma are not diagnostic so cytomorphology , and immunohistochemistery study are needed to differentiate nephrogenic adenoma from malignant lesions , and to avoid erroneous therapeutic approach . nephrogenic adenoma is typically positive for cytokeratin 7 ( ck7 ) , -methylacyl coa racemase ( amacr ) ( p504s ) , pax2 and epithelial membrane antigen ( ema ) , and are usually negative for p63 , cytokeratin 20 ( ck20 ) , and prostatic specific antigen ( psa ) . a 55-year - old female was admitted to shahid faghihi hospital , shiraz , iran with chief complaint of irritative lower urinary tract symptoms and intermittent gross hematuria . four years ago she had developed renal stone , and had been subjected to percutaneous nephrolithotomy . her urine analysis showed red urine containing a large number of red and white blood cells , and few bacteria . cystoscopic examination revealed a sessile 33 centimeters lesion in the left lateral wall of bladder . microscopic examinations of hematoxilin eosin - stained slides showed irregular proliferation of small tubules , which were lined by single - layer low cuboidal epithelium in myxoid and inflammatory background in the lamina propria ( figure 1 ) . there were also some cord - like structures and single cell proliferation . the tissue sections deparaffinized and treated with 3% hydrogen peroxide and antigen retrieval was done . the slides were then stained with a polymer - based detection system ( dako`s envision system ) . immunohistochmistery study showed positive reactivity for p504 , cd10 , ema and ck7 ( figures 2 , 3 , 4 ) , but negative reactivity for psa , p63 and ck20 ( figures 5 , 6 ) . after five months follow up the patient showed decreased complaints , but she did not completely recovered and she did not come back for treatment either . nephrogenic adenoma is a rare bladder lesion presented with well - defined mass located mostly beneath the epithelium . in the past , it was believed that nephrogenic adenoma represented metaplasia of the urinary epithelium in response to inflammatory process . however , it has been demonstrated to result from urothelial shedding , and implant in injured area . adenocarcinoma of the bladder was reported to occur two year after nephrogenic adenoma in a 25-year - old man . few reports have examined the use of immunohistochemical findings in the diagnosis of nephrogenic adenoma . alsanjary et al . studied the morphological and immunohistochemical features for differential diagnosis of nephrogenic adenoma from clear cell adenocarcinoma . immunohistochemical study can differentiate nephrogenic adenoma from malignant process , and define the origin of adenoma . immunohistochmistery studies have shown that pax2 was positive only in remnant of fetal renal tubules and nephrogenic adenoma , and negative in malignant process such as prostatic adenocarcinoma . cytoplasmic staining for ck7 and absence of staining for psa is in favor of nephrogenic adenomaalpha - methylacyl - coa racemase ( amacr , p504s ) , which is the most useful marker for the diagnosis of prostatic adenocarcinoma , is detected in nephrogenic adenoma of urinary bladder . there are some problems in the differential diagnosis of nephrogenic adenoma from clear cell carcinoma of bladder , because it shows foci with tubular , cystic and papillary configuration , but no dysplastic changes . olivia and young reviewed 80 cases of nephrogenic adenoma , which showed a trend of male predominance . jalpota reported an extensive involvement of bladder by nephrogenic adenoma in patient with renal allograft transplant . nephrogenic adenoma is a benign metaplastic response to urothelial injury , and may mimic malignant process . in the present case bladder biopsy was done with high suspicion for malignant lesion . however , immunohisthochmical examination of the biopsy revealed positive findings for ck7 , ema , cd10 and amacr , and negative findings for psa , p63 and ck20 . the clinical and cystoscopic characteristics of nephrogenic adenoma are not diagnostic so cytomorphology , and immunohistochemistery study are needed to differentiate nephrogenic adenoma from malignant lesions and to avoid erroneous therapeutic approach . some cases of nephrogenic adenoma are associated with diagnostic difficulty using certain histologic features , since they may mimic some features of malignant lesions .

nephrogenic adenoma is a rare benign lesion of bladder that may be confused with malignant lesions . there is a strong relation with urinary tract irritation and intravesicle instrumentations . nephrogenic adenoma was initially thought to originate from urothelial metaplasia ; however , no solid proof is available . we present a case of 55-year - old lady with urinary problem . cystocopic examination showed a sessile mass , and biopsy revealed circumscribed proliferation of tubules , cysts , and papillae that were lined by low cuboidal to columnar epithelial cells . nephrogenic adenoma can be a significant diagnostic pitfall due to the presence of certain histological features such as the presence of enlarged nuclei with prominent nucleoli . immunohistochemistery study was strongly positive for ck7 , p504s , cd10 , and ema , but negative for ck20 , psa , and p63 .

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gastrointestinal stromal tumors ( gists ) are the most common mesenchymal , nonepithelial tumors of the gastrointestinal tract in adults between 40 and 50 years of age [ 1 , 2 ] . as per seer analysis , only 1% of 1,458 gist cases are esophageal in origin , with an incidence of 5170% in the stomach ; 2536% in the small intestine ; 57% in the colon , rectum and appendix , and 13% in the esophagus [ 1 , 2 , 3 ] . they are generally small and asymptomatic , but occasionally can be large and produce dysphagia . a review of the literature revealed a case of a large esophageal gist presenting with dyspnea . however , here we report a rare case of a small esophageal gist in a patient with dyspnea who presented with a mediastinal mass on chest x - ray and was initially diagnosed by a pathologist as having leiomyosarcoma and referred for chemotherapy . 1 ) . a ct scan of the chest with contrast revealed a hypodense , soft tissue mass / lymphadenopathy in the posterior mediastinum measuring 2.0 3.0 cm , contiguous with the esophagus ( fig . 2 ) , suggestive of neoplastic etiology . further imaging with pet revealed a mediastinal soft tissue mass / lymph node and a standardized uptake value ( suvmax ) of 5.1 . the patient underwent a bronchoscopy and mediastinoscopy with fine - needle aspiration of the mass . pathology showed increased cellularity with moderate nuclear atypia and pleomorphism with a mitotic count of 23 mitoses/10 high - power fields . the ki67 index was 35% and , finally , the sample was reported as spindle cell well - differentiated leiomyosarcoma ( fig . the patient was referred to us for further management . given the possibility of a gist , thoracotomy findings showed the mass in the posterior mediastinum , which was dissected free from the trachea and inferior aspect of the aorta . six weeks after surgery , a repeated pet - ct scan showed no recurrence . on further follow - up gists are rare , accounting for 0.13.0% of all gastrointestinal neoplasms and 5.7% of sarcomas . initially , gist applied to neoplasms displaying only c - kit ( cd117 ) , but the diagnosis is based on histopathology and immunohistochemistry . a total of 95% of gists express kit or dog 1 and have mutations in kit or platelet - derived growth factor receptor , polypeptide . the kit - positive cells in abdominal soft tissues include mast cells in the wall of the gastrointestinal tract ; the interstitial cells of cajal ( intestinal pacemakers ) around the myenteric plexus were thought to be the origin of gists . gists typically present in adults 4050 years of age and predominantly in the stomach and intestine . a comprehensive review of 11 case reports ( table 1 ) and case series with esophageal gists showed that only 1 patient presented with dyspnea and a large posterior mediastinal mass ( 27 cm ) ; 3 further masses were detected on routine chest x - ray [ 3 , 4 ] . our patient presented with vague , progressive shortness of breath , with the unusual finding of a small mediastinal mass on chest x - ray . esophageal gists commonly present with dysphagia but bleeding , perforation , back pain , anorexia , regurgitation and weight loss have been reported . dyspnea with the finding of a small tumor on chest x - ray is rare . further , pet - ct can help to differentiate gists from sarcoma , but our case showed an suvmax of 5.1 which can misclassify it as sarcoma [ 3 , 8 ] . initial biopsy and testing created a diagnostic dilemma because immunohistochemistry did not include cd117 immunostaining and diagnostic imaging was inconclusive . we present this case to raise physician awareness of such a rare presentation , so that the possibility of gists is considered in these situations , and cd117 testing be done if sarcoma histology is obtained . surgery is the mainstay of treatment of localized gists ; targeted therapies like imatinib have shown overall survival benefit in high - risk patients after surgery [ 9 , 10 ] . and in unresectable and metastatic disease , it has been approved as primary treatment . the pdgfra mutation d842v , sporadic wild - type gists , mutations with succinate dehydrogenase or braf - mutated gists are unlikely to respond to imatinib . ongoing trials involve sorafenib , nilotinib , pazopanib , regorafenib and cediranib for advanced gists [ 11 , 12 , 13 , 14 , 15 ] . future trials with combined or sequential use of tyrosine kinase inhibitors with other medications and personalized therapy after tumor molecular subtyping are promising in the management of gists . our case report highlights the consideration of gists in the differential diagnosis of posterior mediastinal masses and emphasis on the necessity of cd117 staining in those situations which can alter the therapeutic and prognostic implication for the patient .

gastrointestinal stromal tumors ( gists ) are the most common mesenchymal tumors of the gastrointestinal tract and are predominant in the stomach and intestine but rare in the esophagus . here , we report a case of esophageal gist which presented as a mediastinal mass on chest x - ray and dyspnea . the case was initially diagnosed as leiomyosarcoma , which could create a diagnostic dilemma . therefore , recognizing this uncommon presentation as a mediastinal mass with esophageal gist is important in the differential diagnosis .

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cutaneous hyperpigmentation is a recognized adverse effect of chronic minocycline use occurring in up to 50% of patients , . in a recent study performed at the mayo clinic , 54% of 291 patients receiving long - term minocycline suppression for orthopedic infections developed some degree of hyperpigmentation after a mean follow - up of 4.8 years . in this cohort , factors associated with minocycline - induced cutaneous hyperpigmentation ( mich ) include a history of vitamin d deficiency , presence of a shoulder prosthesis , noncirrhotic liver pathology , and use of a concurrent medication ( e.g. , calcium channel blocker ) also known to cause hyperpigmentation . mich is not associated with adverse clinical effects , and it is mostly cosmetic in nature . we herein present a rare case of extensive skin hyperpigmentation involving both lower extremities in a patient receiving long term minocycline . in june 2016 , a 76-year - old male with a past medical history significant for nephrolithiasis and diverticulitis , presented to the authors institution with extensive hyperpigmentation involving both lower extremities . he underwent a left total knee arthroplasty in 1988 at an outside institution and underwent revision surgery in 1992 . in 2001 , he underwent a second revision for fractured patella that was complicated by an infection with a coagulase - negative staphylococcus . he received six weeks of treatment with parenteral vancomycin followed by oral trimethoprim - sulfamethoxazole . operative cultures from the knee grew enterococcus sp . , prevotella sp , viridans group streptococcus , as well as candida parapsilosis . after completing antimicrobial treatment with vancomycin , ertapenem and fluconazole , he underwent reimplantation using a rotating hinged knee arthroplasty in september 2005 ( fig . since that time , the patient was maintained on oral minocycline chronic suppression . in 2010 he uses a brace as well as a cane to ambulate . at a follow - up in february 2012 when he was seen again in june 2016 , there was extensive blue - gray pigmentation in both cheeks and in the lower extremities ( fig . 2 ) , as well as sub - ungual blue - gray pigmentation in both hands ( fig . there are three types of pigmentation patterns that can result from taking minocycline for long periods of time . type i is a blue - gray pigmentation occurring around areas that were previously inflamed . type ii has the same appearance as type i and covers areas of normal skin such as the anterior shins , arms , and ankles . type iii is a muddy brown pigmentation usually occurring on areas of the skin that are exposed to the sun . the blue - gray pigmentation is due to the deposition of iron within the dermal macrophages . the diffuse hyperpigmentation seen in the patient presented in this case report includes both types i and ii . blue - gray pigmentation is clearly seen around the scar on the left knee from his knee replacement surgery ( type i ) . hyperpigmentation is also distinctly seen on the shins of both legs and around the ankles of the patient ( type ii ) . hyperpigmentation is predominantly seen with minocycline and less likely to occur with other tetracyclines such as doxycycline . minocycline is five times more lipophilic than doxycycline ; hence , central nervous system adverse events are more common with minocycline . although doxycycline may have a higher incidence of gastrointestinal upset and photosensitivity , minocycline has an increased likelihood of severe and permanent cosmetic adverse events and central nervous system adverse events . in the study of orthopedic patients on long - term minocycline suppression , these side effects are an addition to gastrointestinal adverse effects that can also occur with minocycline . in the absence of data to show that minocycline is superior to doxycycline for long - term suppression of infections including orthopedic infections , the authors propose that doxycycline be looked upon favorably when chronic use is indicated .

cutaneous hyperpigmentation is a recognized adverse effect of chronic minocycline use occurring in up to 50% of patients . in this report we present a rare case of extensive skin hyperpigmentation involving both lower extremities in a patient receiving long term minocycline . the patient was receiving minocycline as suppression for chronic prosthetic joint infection . risk factors associated with minocycline - induced cutaneous pigmentation ( mich ) will be reviewed .

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in this issue of critical care , protti and colleagues report the effects of metformin on human platelets both in vitro and ex vivo . in vitro experiments were performed on healthy platelets incubated with increasing doses of metformin , whereas ex vivo experiments were done on platelets from patients presenting accidental metformin - induced lactic acidosis . in both situations , platelets ' lactate production and mitochondrial functions were measured . in vitro , a dose - dependent relationship between metformin con centration and lactate production was found . in both conditions , high levels of metformin decreased mitochondrial respiratory chain complex i activity , mitochondria polarization , and oxygen consumption . metformin is a biguanide that has been used as a first - line drug for type 2 diabetes treatment since 1957 in europe and 1995 in the us . metformin was reputed to induce lactic acidosis , partly because phenformin , another biguanide , was withdrawn from the market because of an unacceptable rate of this complication . however , numerous clinical studies reported a similar incidence of lactic acidosis in diabetic patients with or without metformin , leading some authors to deny the existence of metformin - associated lactic acidosis . however , in usual clinical practice , metformin contraindications are not often respected . moreover , physicians do not really monitor adequately their prescription . as a result , numerous publications reported the association between metformin and lactic acidosis . when a cause of lactic acidosis such as shock state or acute renal failure is present , the responsibility of metformin could be questioned . but when healthy patients without risk factors develop metformin poisoning leading to lactic acidosis , there is no doubt about this link . however , metformin inhibits hepatic gluconeogenesis in different animal species and decreases mitochondrial respiratory chain complex i activity in different organs . the clinical research on metformin - associated lactic acidosis was limited to retrospective studies describing incidence , risk factors , and supportive treatments . a big step forward was made when the gattinoni group reported a decrease in oxygen consumption after metformin poisoning in humans , strongly suggesting that metformin was able to induce mitochondrial dysfunction in humans . the study by protti and colleagues elegantly confirms the implication of mitochondria in the pathophysiology of this disease . of course , the importance of platelet mitochondrial dysfunction per se has to be put in perspective . however , as demonstrated previously in the pig , platelet mitochondrial dysfunction mirrors the mitochondrial dysfunction in other vital organs . platelets are more easily accessible than vital organs like the liver or kidney . for research purposes in humans now that serious research on this rare disease has started , we can also imagine improving its care . currently , the treatment is only supportive : increasing blood pressure with fluid infusion and catecholamines and promoting metformin elimination by renal replacement therapy . restoring atp production during energy failure due to mitochondria dysfunction is still challenging . another condition associated with mitochondrial dysfunction , succinate can bypass respiratory chain complex i inhibition and restore oxygen consumption . in isolated cells , succinate is reputed not to cross the plasma membrane , but methyl succinate ( a cellpermeant succinate ) has been used to bypass metformin blockade of respiratory chain complex i .

does metformin - associated lactic acidosis really exist ? despite an old controversy , there is no doubt about it . but do we understand what is going on ? laboratory findings raised several hypotheses explaining the pathophysiology of this disease . the main cause could be an inhibition of either gluconeogenesis or mitochondrial respiratory chain complex i. from bench to bedside , one hypothesis is now confirmed in humans . metformin poisoning involves , at least partially , a mitochondrial dysfunction .

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a 23-year - old female presented with an asymptomatic , erythematous , atrophic macule on the upper right side of her back that increased gradually in size within the last four years without any symptoms ( figure 1a ) . on physical examination the surface of the lesion was smooth and no induration was examined on palpation . dermatoscopic evaluation of the lesion using 3gen dermlite - ii pro hr and documented with dermlite - foto 3gen ( llc , dana point , ca , usa ) showed a homogenous pigment network on a purplish erythematous background ( figure 1b ) . histopathological examination of h&e ( hematoxylin and eosin ) stained sections revealed epidermal atrophy , increase in melanin in basal keratinocytes and heavy dermal cellular infiltrate composed of spindle - shaped cells arranged in a storiform pattern that extended into the subcutaneous tissue ( figure 2 ) . immunhistochemical staining for cd34 was positive , while factor xiiia was negative ( figure 3a , b ) . dfsp is a rare , slow growing , locally invasive cutaneous neoplasm of fibrohistiocytic origin with intermediate grade malignancy with an incidence between 0.85.0 cases per 1 million persons per year . the atrophic presentation of dfsp is the rarest variant of this infrequent neoplasm , which was first described in 1985 . the non - protuberant dfsp can be considered the early clinical stage of dfsp before developing the typical protuberant feature unless it remains as a non - protuberant tumor that is called atrophic dfsp . it occurs as an atrophic , asymptomatic plaque that can be difficult to distinguish from morphea , morphea like basal cell carcinoma , scar , lipoatrophy and atrophic dermatofibroma . although the clinical appearance of atrophic dfsp is different from common protuberant type , histopathological features are similar . atrophic presentation of the lesions may be due to the marked cellularity of the tumor cells in the dermis and infiltration to the subcutaneous fat . immunhistochemical staining is important to distinguish dfsp from atrophic dermatofibroma and medallion - like dermal dendrocyte hamartoma . while dfsp cells are positive for cd34 and negative for factor xiiia , atrophic dermatofibroma cells are usually negative for cd34 and both of cd34 and factor xiiia are positive in the medallion - like dermal dendrocyte hamartoma [ 3 , 4 ] . dermatoscopic studies of dfsp are very rare in the literature . in 2013 , bernard et al reported the first study of dermatoscopic analysis of dfsp in 15 cases . delicate pigment network , vessels , structureless light brown areas , shiny white streaks , pink background coloration and structureless hypopigmented or depigmented areas were defined as six main dermatoscopic features of dfsp . in 2014 , dermatoscopic features such as peripheral dilated vessels forming a mesh - like pattern , milky - red areas , whitish linear structures and fine pigment network were reported in a series of four cases of dfsp . to our knowledge , only one case of atrophic dfsp was presented with dermatoscopic features in the literature . the reported dermatoscopic findings of that case were branching vessels on a yellowish background without pigment network . the authors suggested that the dermatoscopic features might be the result of dermal atrophy and close approximation the subcutis to the epidermis . in contrast , our case showed dermatoscopically regular brown lines reticular on a purplish erythematous background . homogenous brown lines reticular seen in our case correspond to the accumulation of melanin in basal keratinocytes , while the erythematous background is the result of dilated vessels in the dermal plexus . here , the smooth surface reflects the stratum corneum being normal . the most frequent dermatoscopic pattern associated with dermatofibromas , a well - known and benign cousin of dfsp , is the central white scar - like patch and peripheral delicate pigment network . the histopathologic correlation of white scar - like patch in dermatofibroma is pronounced fibrosis within the papillary dermis . contrary to dermatofibromas , fibroplasia in the upper half of the dermis is uncommonly observed in dfsp which may explain the absence of white scar - like areas in our case . in conclusion , we have presented the dermatoscopic findings in an unusual case of atrophic dfsp . atrophic dfsp should be kept in the differential diagnosis for atrophic and depressed skin lesions , particularly those seen on the trunks of women . dermatoscopy , a noninvasive method , may not only help to differentiate atrophic dfsp from other skin diseases but may also indicate the need for histopathological examination since the disease has prognostic significance .

dermatofibrosarcoma protuberans ( dfsp ) is an uncommon locally aggressive mesenchymal tumor with a high local recurrence rate . atrophic dfsp is a rare variant of dfsp characterized by a non - protuberant lesion . we report on a 23-year - old female , who presented with an atrophic , asymptomatic macule on the right side of her back 2 cm in diameter . dermatoscopic examination revealed homogenous pigment network on a purplish erythematous background . the histopathological finding of the incisional biopsy material was consistent with dfsp . to our knowledge , this is the second case of atrophic dfsp discussing the dermatoscopic features of this relatively rare condition .

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for the past 50 years disulfiram is the commonly prescribed drug for the treatment of alcohol dependence . important side effects of disulfiram are hepatological , dermatological , neurological ( polyneuritis , encephalopathy)1,2 ) and psychiatric in nature . psychiatric manifestations include confusion , loss of memory , psychosis,36 ) mania with psychotic symptoms.7,8 ) disulfiram s major metabolite diethyldithiocarbamate is an inhibitor of dopamine - betahydroxylase ( dbh ) , an enzyme that catalyzes the metabolism of dopamine ( da ) to norepinephrine ( ne).9 ) by inhibiting this metabolic pathway from da to ne in the central nervous system , disulfiram results in an increase of da concentrations in mesolimbic system resulting in psychosis . alcoholics who developed psychotic symptoms during disulfiram treatment are found to have low levels of amine and monoamine oxidase , suggesting dbh blockage.10 ) we present a case of 32-year - old male who developed psychosis with the use of disulfiram . a 32-year - old male without past of psychiatric and neurological illness reported to psychiatry outpatient department with complaint of daily alcohol intake of 250750 ml ( 40% alcohol by volume ) for the last 5 years . with the informed consent of the patient , disulfiram was administered at the dosage of 250 mg twice daily for 1 month , while the patient abstained from alcohol . then the patient presented complaint of fearfulness , suspiciousness , easy irritability , muttering to self , decreased sleep for last one month . haematological and biochemical indices were within normal limits . on mental status examination delusion of persecution and auditory his fearfulness , suspiciousness , irritability , muttering to self and impaired sleep gradually improved over a period of 10 days . risk factors for development of disulfiram related psychotic symptoms include past history or family history of psychosis , overly rapid increase in dosage or greater than recommended total dosage , old age , impaired liver function and concurrent dopaminergic medications or psycho - stimulant abuse.5,11 ) our patient has family history of schizophrenia in his father . his psychotic symptoms improved after stoppage of disulfiram and use of lorazepam tablet only without any additional requirement of anti - psychotic treatment . these factors support the association between with disulfiram use and emergence of psychotic symptoms in our patient . the usual recommended initial dosage is 500 mg per day for the first 1 or 2 weeks , followed by a maintenance dosage of 250 mg per day.12 ) disulfiram related psychosis usually involve either therapeutic or higher than recommended dosages.13 ) our patient has developed psychotic symptoms with 500 mg per day of disulfiram . we recommend that disulfiram should be used at the lowest effective dose , possibly 250 mg daily . our case highlights the relevance of a careful history of patient s symptoms and family history that should be performed before starting treatment with disulfiram and caution should be taken while prescribing disulfiram for patients with personal and familial antecedents of psychosis . disulfiram - related psychiatric complications are reported to be more prevalent in eastern countries,3 ) which suggests that genetic factors may play a role in disulfiram induced psychosis .

disulfiram is the commonly prescribed drug for the treatment of alcohol dependence . it s major metabolite ( diethyldithiocarbamate ) is an inhibitor of dopamine - betahydroxylase , an enzyme that catalyzes the metabolism of dopamine to norepinephrine resulting in psychosis . we recommend that disulfiram should be used at the lowest effective dose , possibly 250 mg daily and caution should be taken while prescribing disulfiram for patients with personal and familial antecedents of psychosis .

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a 59-year - old man presented with a swelling of the left lower extremity that had begun two months earlier . for further evaluation , we performed computed tomography ( ct ) venography and pelvic magnetic resonance imaging ( mri ) . the ct venography axial images showed a 2.3 cm cystic mass compressing the left common femoral vein ( fig . the mri images showed a cystic mass compressing the left common femoral vein as well ( fig . we suspected adventitial cystic disease ( acd ) of the common femoral vein , and the patient underwent an operation . under general anesthesia in a supine position , the femoral artery and vein were dissected for about 5 cm with a longitudinal incision on the left inguinal area . surgical exploration showed an approximately 2.0 cm sized cystic mass that originated from the adventitia of the common femoral artery and was compressing the common femoral vein . the cyst that had adhered to the femoral artery was removed first , and the part of the wall that was attached to the cyst in the femoral artery was partially resected . angioplasty was performed to repair the femoral artery whose wall was partially resected . because the patient had had a partial circulation problem in the vein before the surgery and thus venous obstruction was possible , a polytetrafluoroethylene ( ptfe ) patch was used for angioplasty instead of using an autologous vein graft . a cystic mass excision with ptfe roofing angioplasty microscopically , the presence of a mucinous cyst and vessel wall degeneration confirmed cystic adventitial disease of the common femoral artery ( fig . acd is an unusual cystic tumor of the blood vessels characterized by the accumulation of a mucinous substance in the adventitia . acd is an uncommon disease that was first described in 1947 by atkins and key . acd accounts for only 0.1% of cases of vascular disease , and among them , 85% of all cases of acd occur in the popliteal arteries , while fewer cases appear in the femoral arteries . the first case of common femoral artery acd was reported by jaquet and meyer - burgdorff in 1960 . it was reported that the prevalence is 5 times higher in males than in females . the age of occurrence ranges from 11 to 72 years , and the average age is 42 . four theories have been proposed about the nature of acd : 1 ) the theory that it is a systemic disorder of the connective tissue ; 2 ) the theory that it is a chronic degenerative change due to repetitive trauma ; 3 ) the developmental theory , which maintains that a joint - related ganglion - like structure is incorporated into the vessels during embryologic development ; and 4 ) the ganglion theory that arterial adventitial cysts originate from joint capsular synovial structures . thus continuous trauma from using fishing tools in contact with the thighs was suspected to have contributed to the lesion . on the other hand , considering that the lesion occurred unilaterally and did not appear on the opposite thigh , repetitive trauma is not an obvious explanation for the lesion . the symptoms of acd can include unilateral claudication of the lower extremity , and in rare cases it shows ischemic neuropathy such as paresthesia , pain , and rhigosis . other possible symptoms include arterial obstruction that results in the pulse in the femoral , the popliteal , and the dorsal pedis arteries being weak or not palpable . however , the main symptom in our case was the uncommon occurrence of swelling that appeared due to the venous obstruction . in addition , the pulse of the blood vessels of the lower extremities was fully palpable . recently , it has been accepted that angiography using 3-dimensional ct alone is now considered sufficient for diagnosis . ct angiography is considered to be an important test because it not only determines the site and extent of stenosis but is also useful in evaluating the entire circulation system . aspiration of the cyst under ct or ultrasonography is a minimally invasive method , but it is difficult to perform and the cyst has a high recurrence rate . this method also has a higher recurrence rate than complete resection involving the vessel with artificial material interposition . interposition provides better long - term patency than the other methods . in this case , in the pre - surgical assessment the lesion was misdiagnosed as originating from the femoral vein instead of from the femoral artery . in addition , recurrence will be minimized by our having performed the arterial repair and interposition as well as the cystic mass excision . thus we report here a case of acd , a rare disease , with unusual symptoms , that was successfully treated with surgery .

arterial adventitial cystic disease is an uncommon type of non - atherosclerotic peripheral vessel disease . most cases of arterial adventitial cystic disease occur in the popliteal arteries ; however , fewer cases have been reported in the femoral arteries . a 59-year - old male patient visited the hospital with a complaint of a swelling on the lower extremity that had begun two months earlier . suspecting deep vein thrombosis based on a physical examination and ultrasonography from another hospital , tests were performed . magnetic resonance imaging ( mri ) was performed for exact diagnosis because venous adventitial cystic disease was suspected by computed tomography venography . the mri indicated venous adventitial cystic disease as well . thus , a cystic mass excision was performed . in the end , a cystic mass compressing the common femoral vein that originated from the common femoral artery was diagnosed based on the macroscopic findings . this case is reported because blood circulation in the vein was impeded due to arterial adventitial cystic disease , and the symptoms improved after the cystic mass excision and polytetrafluoroethylene roofing angioplasty .

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transgenic ostreococcus tauri lines4 were cultured in keller media - supplemented artificial sea water ( km ) under 12:12 h blue ( ocean blue , lee lighting filter 724 ) light : dark cycles ( 17.5 e / m ) . for imaging , cultures were transferred to 96-well microplates ( lumitrac , greiner bio - one ) at a density of ~1510 cells / ml and entrained for 7 - 10 days . no density effects on clock output were observed under relevant density ranges , and cell division in microplates was found to be close to zero . one day prior to recording , 150 l km was replaced with 150 l km containing 333 m luciferin ( km+ ) . drugs were made up in dmso or km+ , diluted in km+ and added to replicates of 8 or 16 wells immediately prior to recording . for incubations in constant darkness , km+ was supplemented with 200 mm sorbitol and 0.4% glycerol in order to increase cell viability . bioluminescent recordings were performed on a topcount ( packard ) under constant darkness or constant red+blue led light ( 5 - 12 e / m ) . for wash - off of reversible inhibitors , cell aggregates formed in the bottom of the wells were quickly and gently washed twice with km+ , using multi - channel pipettes , and returned to recording conditions . analysis of period was performed with fft - nlls ( brass 330 ) using time windows 3 days ; mfourfit ( brass 3 ) was used to assess phase and confirmed manually . statistical analysis was performed using graphpad prism . for de novo rna synthesis analysis by [ p]utp uptake , 1 ml cell aliquots were either incubated in darkness or light / dark cycles for 4 days . 0.2 mbq of [ p]utp was added , and after incubation cells were collected and washed twice with km . sequence alignments were performed using ebi jalview , blast searches were performed using ncbi blastp under the default blossum62 settings . circadian rhythms in a eukaryote can be sustained solely by non - transcriptional mechanisms , which are conserved across taxa .

circadian rhythms are ubiquitous in eukaryotes , and co - ordinate numerous aspects of behaviour , physiology and metabolism , from sleep / wake cycles in mammals to growth and photosynthesis in plants1,2 . this daily timekeeping is thought to be driven by transcriptional / translational feedback loops , whereby rhythmic expression of clock gene products regulates expression of associated genes in approximately 24-hour cycles . the specific transcriptional components differ between phylogenetic kingdoms3 . the unicellular pico - eukaryotic alga , ostreococcus tauri , possesses a naturally minimised clock , which includes many features that are shared with higher eukaryotes ( plants ) , such as a central negative feedback loop that involves the morning - expressed cca1 and evening - expressed toc1 genes4 . given that recent observations in animals and plants have revealed prominent post - translational contributions to timekeeping5 , a reappraisal of the transcriptional contribution to oscillator function is overdue . here we show that non - transcriptional mechanisms are sufficient to sustain circadian timekeeping in the eukaryotic lineage , though they normally function in conjunction with transcriptional components . we identify oxidation of peroxiredoxin proteins as a transcription - independent rhythmic biomarker , which is also rhythmic in mammals6 . moreover we show that pharmacological modulators of the mammalian clockwork have the same effects on rhythms in ostreococcus . post - translational mechanisms , and at least one rhythmic marker , appear to be better conserved than transcriptional clock regulators . it is plausible that the oldest oscillator components are non - transcriptional in nature , as in cyanobacteria7 , and are conserved across kingdoms .

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a 27-year - old man visited our hospital because of a sudden - onset generalized convulsion . he had been overworking and had slept less than 5 hours a day for the previous month . a week prior to the hospital visit , the patient had developed a fever and generalized myalgia but had not taken any medicine . high fever , anorexia , and generalized malaise appeared . on the day of the hospital visit , he could not be awakened , and he showed no responses to any stimulus . finally , he developed a generalized tonic - clonic seizure that lasted for about three min and that was accompanied by cyanosis , upward eyeball deviation , and tongue biting . on physical examination at the emergency department , the patient s body temperature rose up to 38.7c . he was confused and could not follow the examiner s verbal commands appropriately , and he often attempted to run out of the bed while yelling incomprehensible words and abuses . neck stiffness was found on neurologic examination . positive or negative myoclonic jerk was not observed . the cerebrospinal fluid ( csf ) was clear , and its pressure was measured at 16.0 cmh2o , with 20 leukocytes/l ( 95% lymphocytes ) , protein levels of 70.5 mg / dl , and normal glucose levels ( 63.0 mg / dl ) . aspartate aminotransferase ( ast ) , alanine aminotransferase ( alt ) , and -glutamyl transpeptidase levels were increased to 441 , 1294 , and 460 total bilirubin and direct bilirubin levels were normal ( 0.6 mg / dl and 0.2 mg / dl , respectively ) . seizure did not relapse after 30 min of continuous infusion of 15 mg / kg of phenytoin mixed with normal saline . he regained consciousness on the second admission day and became fully conscious the following day . intravenous acyclovir was given for two days because of the clinical suspicion of herpes encephalitis , which was discontinued after observing the clinical improvement and the detection of the igm antibody of hav . the patient s score on the korean version of the mini - mental status examination ( k - mmse ) score was 30 on the fifth admission day . serum and csf igm antibodies of herpes simplex type 1 , 2 , and varicella zoster were negative . polymerase chain reaction ( pcr ) of the csf for hav and enterovirus were also negative . ast and alt levels decreased to 125 and 432 iu / l on the seventh admission day . hav , which causes an acute inflammatory hepatitis , is a picornavirus , which is transmitted by the fecal - to - oral route . the clinical spectrum varies from mild flu - like illness to fatality caused by acute fulminant hepatitis . in the anicteric form , diagnosis may be delayed due to the atypical presentation of the disease . in general , the disease is preceded by flu - like prodromes , and the progression of the hepatitis symptoms and liver enzyme elevations is relatively rapid . in a week or so , liver enzymes stop elevating and gradually decrease to normal levels . diagnosis can be made by the detection of the serum igm antibody of hav [ 46 ] . common pathomechanisms are attributed to a disturbed detoxification process by the damaged liver and metabolic disturbances , such as fluid electrolyte imbalances . our patient had a seizure in an early stage of the disease , and he showed no specific laboratory abnormalities other than liver enzyme elevations . he showed neck stiffness and a clouding of consciousness that was accompanied by csf abnormalities that were compatible with encephalitis . these findings support the diagnosis of encephalitis rather than that of toxic - metabolic disturbances due to the hepatitis . after reviewing five cases , including the above report , altered consciousness and seizures are commonly manifested . positive hav pcr results were reported in one case , of which csf cells and protein were normal . the clinical courses were all benign ; all patients improved within a few days to a few weeks with supportive treatment [ 2,3,810 ] . hav - associated encephalitis is a very rare disorder , which has not been reported in korea . no specific radiological or eeg findings are observed . in particular , in the anicteric form of the disease , the diagnosis may be difficult without a clinical suspicion . when progressive liver enzyme elevations are observed in patients with encephalitis

encephalitis is caused by multiple organisms , but rarely by the hepatitis a virus . a 27-year - old man visited our hospital because of fever , altered consciousness , and seizures . on physical exam , a stuporous mentality and neck stiffness were found . on laboratory exam , elevated liver enzymes and cerebrospinal fluid abnormalities , including pleocytosis and elevated protein levels were observed . the hepatitis a virus ( hav ) igm antibody was also detected . we conclude that these findings were compatible with encephalitis associated with hav and discuss the pathomechanisms .

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busy clinicians sometimes think twice before reading studies of animal models . yes , it sounds interesting , but is it really going to change my practice ? there is so much else i should be reading ... this writer does not mean to cast aspersions on such an attitude - and , in fact , share sit , at least to some extent . the report in the previous issue of critical care by bangash and colleagues is one such study . dopexamine is a dopamine analog that stimulates -adrenergic and dopamine 1 and 2 receptors , conferring some vasodilatory effects . dopexamine has classically been considered a vasoactive agent with inotropic effects , perhaps with more prominent effects in some regional vascular beds . as such , dopexamine has been tested in clinical trials to optimize hemodynamics , either in patients with shock or as part of a perioperative regimen . myocardial dysfunction occurs in a subset of patients with septic shock , so a strategy of increasing cardiac output and thus oxygen delivery in this setting made some sense . implementation of this strategy using dobutamine , with or without norepinephrine , to improve cardiac output topredetermined supranormal levels in all patients did not improve outcomes [ 3 - 5 ] , and use of inotropic therapy for this purpose is not recommended in current guidelines . subsequent reports of potentially deleterious proinflammatory effects of catecholamines provided mechanistic support for their lack of efficacy when used indiscriminately . use of dopexamine targeted to increase oxygen delivery to > 600 ml / minute / m , however , was shown in a randomized trial reported in 1993 to decrease mortality in the perioperative period . whether this resulted from differential hemodynamic effects of dopexamine compared with other agents , perhaps selective vasodilation of regional circulations , or whether use of inotropes for perioperative optimization is different from their use in other settings some reports using perioperative dopexamine found reduced morbidity or mortality , confirming the initial study , but others found no difference from conventional treatment [ 10 - 12 ] . a patient - level meta - analysis suggested that some of the differences might be explained by the dose of dopexamine employed . other studies indicated that dopexamine - in part due to 2-adrenergic effects , but also through other pathways - might have immunomodulatory effects , especially in the spleen . the current study investigated both hemodynamic and inflammatory effects of a low dose of dobutamine in a rodent model of endotoxemia . dopexamine reduced the systemic inflammatory response to endotoxin , including cytokine release , endothelial adhesion molecules , and oxidative stress , without substantially changing systemic hemodynamics , either blood pressure or stroke volume . regional flow , assessed by laser doppler in the mesenteric circulation , was also not changed by dopexamine - yet lactate levels and organ function were improved . while immunomodulatory effects of dopexamine were demonstrated in this study , these results contrast with those of a recent clinical investigation , also carried out by this same group , in which dopexamine improved global oxygen delivery , microvascular flow and tissue oxygenation but did not change the inflammatory response to surgery . perhaps the difference could result in part from microcirculatory heterogeneity , something not assessed by the laser doppler methodology used in this study . previous studies have shown that regional heterogeneity may be a good predictor of outcome in shock states , and such heterogeneity might contribute to both perfusion abnormalities and production of lactate in sepsis and other inflammatory states . thus , while this study convincingly demonstrates immunomodulatory effects of dopexamine in this model , it seems possible that microcirculatory hemodynamic effects are also playing a role . this animal study addresses some of the mystery of why effects of dopexamine may differ from those of other catecholamines , but that mystery is not yet fully solved . hemodynamics rule , and those who understand them rock , but this study reminds us that catecholamines have inflammatory effects that must be taken into account when considering their use . animal studies are usually pursued as part of a reductionist approach aimed at controlling as many variables as possible in order to isolate mechanistic effects , but their interpretation and extrapolation to the clinical setting reminds us that in critical care , clinicians think of effects on different systems all together . carefully conducted studies such as this one counteract the nihilistic tendency to think that mechanisms are too complicated and thus only hard clinical endpoints in patients are of any value , and encourage the sort of integrative approach that makes progress possible .

dopexamine is a dopamine analog that has been used for hemodynamic optimization in a number of clinical settings . this animal investigation showed anti - inflammatory effects of dopexamine in a rat endotoxin model without effects on global or regional flow , but it is not time to dispense with hemodynamics altogether just yet . rather , an integrative approach to the effects of catecholamines , considering both inflammatory and hemodynamic effects , including those on the microcirculation , can help clinicians best understand how to employ them in clinical practice .

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emphysematous cystitis is a distinct complicated lower urinary tract infection ( uti ) characterized by air within the bladder wall and lumen . patients with chronic utis , indwelling urethral catheters , urinary tract outlet obstruction , or neurogenic bladders are predisposed to complicated utis such as emphysematous cystitis . air within the urinary tract can also occur due to instrumentation , fistula to a hollow viscus , tissue infarction with necrosis . patients might have varied presentations , ranging from incidental diagnosis on abdominal imaging to severe sepsis . gas - forming infections or emphysematous conditions of the urinary tract are potentially life - threatening , and require prompt evaluation and management . we describe a case of emphysematous cystitis that was managed successfully with bladder drainage , intravenous antibiotics , and strict glycemic control . a 45-year - old male who was a known case of type-2 diabetes mellitus for last 16 years , complained of on and off fever , dysuria and turbid colored urine for last 3 months . he had past history of suprapubic catheterization for obstructive uropathy due to meatal stenosis 15 years back . clinical examination revealed pallor , penile hypospadias , meatal stenosis , bilateral nonproliferative diabetic retinopathy and evidence of sensory neuropathy . investigations showed anemia ( hb7.7 gm / dl ) , neutrophilic leukocytosis ( total leukocyte count 19800 cells / cmm ( n , 400011000 cells / cmm ) with 90% neutrophils . serum creatinine was 3.5 mg / dl ( n , 0.6 - 1.2 mg / dl ) and hba1c was 8.5% ct abdomen revealed intraluminal and intramural gas in the bladder with thickening of bladder wall [ figure 1a c ] . kidneys were normal in size and shape and there was no perinephric stranding or gas in renal parenchyma or renal pelvis . figure 1d shows disappearance of intramural and intraluminal gas on follow up ct imaging after 8 weeks . serum creatinine was decreased to 2 mg / dl , but not normalized probably because of underlying diabetic nephropathy . ( c ) axial ct image through lower pelvis showing pneumobladder , intramural air and circumferential mural thickening . ( d ) axial ct image through lower pelvis after treatment showing disappearance of air ; however , mural thickening is persisting other organisms reported include klebsiella pneumoniae , pseudomonas aeruginosa , proteus mirabilis , candida albicans , and candida tropicalis , aspergillus fumigatus , staphylococcus aureus , group d streptococcus , enterococcus faecalis , enterobacter aerogenes , and clostridium perfringens and cl . the clinical presentation of emphysematous cystitis is varied ; patients can be asymptomatic , describe pnematuria , or irritative voiding symptoms , or present with an acute abdomen with severe sepsis . of reported patients with emphysematous cystitis , predisposing factors for emphysematous cystitis include diabetes mellitus , neurogenic bladder , lower urinary tract obstruction , urethral catheter placement , vesicourethral reflex , and end stage renal disease . the effects of diabetes mellitus on the urinary tract include diabetic nephropathy , renal papillary necrosis , renal artery stenosis , and bladder dysfunction secondary to neuropathy . these factors combined with glycosuria and impaired leukocyte function place diabetic patients at greater risk of complicated utis such as emphysematous cystitis . overall , two - thirds of reported cases of emphysematous cystitis were diabetic and 64% were women . the symptoms of emphysematous cystitis are similar to those of uncomplicated cystitis , consisting of frequency , urgency , and dysuria . therefore , a high index of suspicion is required for diagnosis especially in patients with risk factors . plain radiographs of the abdomen reveal radiolucency within the lumen of the bladder as a ring of radiolucency outlining the bladder wall . computed tomography of the abdomen is superior to plain radiographs as a diagnostic tool because it clarifies the extent and location of the gas collection as observed in our case . a pathological assessment of involved bladder tissue might show bladder wall thickening with vesicles of varying size , and microscopically there are multiple gas filled vesicles predominantly within the bladder mucosa , lined by flattened fibrocytes and multinucleated giant cells . it is thought that the high glucose concentration within the tissues acts as a favourable substrate for organisms to produce carbon dioxide through facultative anaerobic glycolysis . however , this does not account for the significant number of non - diabetic patients with emphysematous infections . in such patients , urinary albumin might act as the substrate for gas production by urinary pathogens . another theory suggests that an impaired host response , involving vascular compromise and impaired catabolism within the tissues , predisposes patients to gas production within these tissues . the pathogenesis is not yet fully understood , but a multifactorial aetiology of impaired host responses with sugar or protein fermentation seems to be a plausible explanation for the production of gas within the affected tissues . management consists of adequate urinary drainage , appropriate antibiotic treatment , and good blood glucose control . however , delayed diagnosis may lead to extension to the ureters and renal parenchyma , bladder rupture , and death . the gas is reabsorbed once the infection is eliminated as was seen in our patient [ figure 1d ] . history of pneumaturia and evidence of intraluminal and intramural gas along with bladder thickening on imaging clinches the diagnosis of emphysematous cystitis .

emphysematous cystitis is a relatively rare clinical entity caused by gas - fermenting bacteria or fungus . presentation is often nonspecific and imaging is the best diagnostic modality . we report a case of a 45-year - old male who presented with fever , dysuria , and pneumaturia , and was found to have emphysematous cystitis .

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transverse testicular ectopia ( tte ) is an uncommon anatomical abnormality in which both the gonads migrate towards the same hemiscrotum . the ectopic testis may lie in the opposite hemiscrotum , in the inguinal canal or at the deep inguinal ring . an inguinal hernia is commonly present on the side to which the ectopic testis has migrated . we present a case of 42-year - old male diagnosed preoperatively as left inguinal hernia with normal ultrasonography findings , who found to have tte on exploration . a 42-year - old married male , having three children , presented to us with history of swelling over left inguinal region for 2 years . the swelling was painless , gradually increasing in size and more prominent on coughing and straining . he was planned for hernioplasty and on exploration , there was a left indirect inguinal hernia with thinned out hernial sac with vas and cord structures of the left side . surprisingly , both testes could be delivered into the wound with their individual vas deferens and cord structures ( fig . 1 ) . both of them were mobilized , followed by right orchidopexy ( of medially located testis ) by passing it through a trans - septal incision . he had an uneventful recovery and on follow - up , he had no complications ; both the testes were normal to feel with no vascular compromise on doppler study . figure 1:exploration of left inguinal region revealed both testes with cord structures on the left side . exploration of left inguinal region revealed both testes with cord structures on the left side . tte , also called testicular pseudoduplication , unilateral double testis and transverse aberrant testicular maldescent , is an uncommon anatomical abnormality in which both the gonads migrate towards the same hemiscrotum . adhesion or fusion of developing wolffian ducts , defective or aberrant gubernaculum , testicular adhesion , defective formation of the internal inguinal ring , traction on a testis by persistent mllerian structures and possibility of the development of both testes from the same germinal ridge , are some of the postulated theories for the ectopic testis . mechanical effect of persistent mllerian duct structures may prevent the testicular descent or lead to both testicles descending towards the same hemiscrotum , producing tte . tte may have an increased risk of malignancy as any other forms of ectopic testis or undescended testis , so long - term follow - up is required . tte is classified into three types based on associated abnormalities : type i : accompanied only by hernia ( 4050%).type ii : accompanied by persistent or rudimentary mllerian duct structures ( 30%).type iii : associated with disorders other than mllerian remnants , e.g. hypospadias , true or pseudohermaphroditism and other scrotal abnormalities ( 20% ) . type iii : associated with disorders other than mllerian remnants , e.g. hypospadias , true or pseudohermaphroditism and other scrotal abnormalities ( 20% ) . patients with tte commonly present as inguinal hernia on one side and absent testis on the other side . the patient had left inguinal hernia and absent testis on the right hemiscrotum , which we could not identify on clinical examination and ultrasonography . one explanation could be that since both the testes were on the left hemiscrotum , the pressure effect of left testis on right one could have pushed the right testis towards further right of the left hemiscrotum giving a false impression on clinical examination that location of right testis was on correct side . there are reports suggesting ultrasonography , ct scan , magnetic resonance imaging and magnetic resonance venography as tools for preoperative diagnosis of tte . the case presented here was managed by orchidopexy of the correctly lateralized testis to the ipsilateral hemiscrotum , and orchidopexy of the crossed testis to the contralateral hemiscrotum through a trans - septal incision , known as the ombredanne procedure . this case is reported with a view that surgeons need to be aware of this anomaly during repair of inguinal hernia , as most cases of tte are diagnosed intraoperatively , hence adequately and safely treat the patient even with tte when discovered unexpectedly , continue long - term follow - up to identify malignancy early , if any . patients with tte need to be treated by restoring the contralateral testis to its original hemiscrotum through a trans - septal incision . written informed consent was obtained from the patient for publication of this case report and related photograph . all three authors were involved in the treatment of the patient and wrote and finalized the manuscript .

transverse testicular ectopia ( tte ) is a rare anomaly that is commonly associated with inguinal hernia . most of the reported cases are in children with very few reported cases in adults . we report a case of 42 years , fertile male , who presented with left reducible inguinal hernia . during surgery , he was found to have a left indirect inguinal hernia with tte with both testes on the left side . hernioplasty and bilateral orchidopexy were performed . he had an uneventful recovery . most of these cases are diagnosed intraoperatively , but imaging ( ultrasonography and magnetic resonance imaging ) has emerged as a promising tool for preoperative diagnosis although ultrasound missed it in this case .

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to evaluate the interactive effects of different self - adhesive resin cements and tribochemical treatment on bond strength to zirconia . the following self - adhesive resin cements for bonding two zirconia blocks were evaluated : maxcem ( ma ) , smartcem ( sm ) , rely x unicem aplicap ( un ) , breeze ( br ) , biscem ( bi ) , set ( se ) , and clearfil sa luting ( cl ) . the specimens were grouped according to conditioning as follows : group 1 , polishing with 600 grit polishing paper ; group 2 , silica coating with 110 m al2o3 particles which modified with silica ; and , group 3 , tribochemical treatment - silica coating + silanization . specimens were stored in distilled water at 37c for 24 hours before testing shear bond strength . silica coating and tribochemical treatment significantly increased the bond strength of the ma , un , br , bi , se and cl to zirconia compared to # 600 polishing . for both # 600 polished and silica coating treatments , mdp - containing self - adhesive resin cement cl had the highest bond strengths to zirconia . applying silica coating and tribochemical treatment improved the bond strength of self - adhesive resin cement to zirconia , especially for cl .

aimto evaluate the interactive effects of different self - adhesive resin cements and tribochemical treatment on bond strength to zirconia.methodologythe following self - adhesive resin cements for bonding two zirconia blocks were evaluated : maxcem ( ma ) , smartcem ( sm ) , rely x unicem aplicap ( un ) , breeze ( br ) , biscem ( bi ) , set ( se ) , and clearfil sa luting ( cl ) . the specimens were grouped according to conditioning as follows : group 1 , polishing with 600 grit polishing paper ; group 2 , silica coating with 110 m al2o3 particles which modified with silica ; and , group 3 , tribochemical treatment - silica coating + silanization . specimens were stored in distilled water at 37c for 24 hours before testing shear bond strength.resultssilica coating and tribochemical treatment significantly increased the bond strength of the ma , un , br , bi , se and cl to zirconia compared to # 600 polishing . for both # 600 polished and silica coating treatments , mdp - containing self - adhesive resin cement cl had the highest bond strengths to zirconia.conclusionapplying silica coating and tribochemical treatment improved the bond strength of self - adhesive resin cement to zirconia , especially for cl .

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a 50 year male presented on july 2011 to the emergency department with right heel pain and inability to bear weight following falling from height . clinical examination revealed mild uniform swelling of the right heel and moderate tenderness with full ankle range of motion . 1 ) revealed undisplaced calcaneal fracture which was treated conservatively and the lesion was not noticed initially . he was followed up in outpatient clinic and the new x - rays ( fig . 2 ) revealed the presence of pathological fracture with a well - defined osteolytic lesion . mri showed a well demarcated expansile lesion ( 34 mm 17.3 mm 27.8 mm ) . it was hypointense on t1 and hyperintense on t2 and the findings were suggestive of giant cell tumor ( fig . 3 ) . lab results including complete blood count , sedimentation rate and c - reactive protein were within normal ranges . after 4 months he underwent curettage of lesion using burrs through posterolateral approach ( fig . histopathological examination revealed multiple bone fragments and the soft tissue infiltrated by multinucleated giant cells , hemosiderin laden macrophages , cholesterol cleft and hemorrhages ( fig . postoperative lipid profile was normal and the diagnosis of primary xanthoma of calcaneus bone was made . postoperatively the patient was well with complete relief of pain and the patient started full weight bearing ambulation after 6 weeks . the patient is still under follow up with no signs of recurrence after 2 years . xanthomatous changes have been reported in various lesions of bone , e.g. fibrous dysplasia , giant cell tumor , aneurysmal bone cysts , non - ossified fibroma , chondroblastoma , fibrous histiocytoma , and xanthogranulomatous osteomyelitis . defined primary xanthoma as a condition in which the xanthomatous pattern is extensive and when it is not confirmed as secondary phenomenon in pre - existing lesion . some authors define this lesion as a variant , because xanthoma and giant cells may be seen in many non - neoplastic and neoplastic lesions of the bone . classification of xanthoma may be helpful to allow diagnosis and treatment:(1)xanthomatous variant : xanthomatous changes in advanced stage of skeletal benign or malignant pre - existing lesions.(2)secondary xanthoma : forms in the skeletal system of type-2 and 3 hyperlipidemic patients.(3)primary xanthoma with normal lipid metabolism . xanthomatous variant : xanthomatous changes in advanced stage of skeletal benign or malignant pre - existing lesions . all material should be examined microscopically , the radiological features of the lesion should be studied properly and lipid profile should be investigated to differentiate between primary and secondary xanthoma . primary xanthoma may be treated with curettage and bone graft while secondary xanthoma is treated nonsurgically and the skeletal manifestations would disappear with systemic treatment of hyperlipidemia . skeletal primary xanthoma is a rare benign lesion and it is difficult to diagnose using only clinical and imaging techniques . detailed histopathological examination throughout the specimens is essential to establish the diagnosis of primary xanthoma and to exclude the underlying lesion . it is important to histologically and radiologically differentiate a primary xanthoma from secondary changes in other benign or malignant tumors . as the prognosis of primary xanthoma is excellent , curettage and bone grafting is an effective way of treatment . written informed consent was obtained from the patient for publication of this case report and accompanying images . a copy of the written consent is available for review by the editor - in - chief of this journal on request . dr . ghalib ahmed : operating surgeon 1 , writing the manuscript and review of literature . moutasim el mahi : obtaining all the patient 's data ( imaging and histopathology ) . sameh abolfotouh : writing the manuscript , reviewing the patient 's file & author of correspondence .

introductionxanthoma ( or xanthofibroma ) is a benign proliferative lesion , mostly seen in soft tissue . xanthoma of bone is very rare benign primary bone tumor , more frequently seen in men and in patients over 20 years of age . histologically , it is characterized by mononuclear macrophage - like cells , abundant foam cells , and multinucleated giant cells . it is sometimes discovered coincidentally and the most frequent symptom is pain.presentation of casewe present a 50-year - old healthy male patient with primary xanthoma of the calcaneus , who was treated by curettage and bone cement . he presented with a pathological fracture in a calcaneus bone lesion . giant cell tumor was suspected on x - ray and mri . curettage and bone cementing was done through the posterolateral approach . lipid profile was normal and histological examination revealed findings consistent with primary xanthoma of calcaneus bone.discussionto avoid an erroneous diagnosis , all material should be examined microscopically , the radiological features of the lesion should be studied properly and lipid profile should be investigated to differentiate between primary and secondary xanthoma . primary xanthoma may be treated with curettage and bone graft while secondary xanthoma is treated nonsurgically and the skeletal manifestations will disappear with systemic treatment of hyperlipidemia.conclusionwe present this case to raise the suspicion of this lesion that is rarely described in the literatures . this is the first case of primary xanthoma of calcaneus bone that has been reported in qatar .

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renal cell carcinoma ( rcc ) comprises 23% of all adult malignancies and 85% of malignant renal tumors . the highest incidence is found in individuals in the sixth and seventh decades of life , 66 being the median age at diagnosis [ 1 , 2 , 3 , 4 , 5 ] . rcc has a strong propensity to metastasize ; 25% of patients initially present with distant metastasis and another 50% develop metastasis during follow - up [ 1 , 6 , 7 ] . it is the third most frequent neoplasm to metastasize to the head and neck region , preceded only by breast and lung cancer [ 1 , 3 , 4 , 5 , 8 , 9 , 10 ] . although infrequently reported , head and neck regional metastases may be linked to rcc in up to 815% of cases [ 1 , 2 , 4 , 6 , 7 , 8 , 9 ] . the most affected regions of the head and neck include the paranasal sinuses , larynx , jaws , temporal bones , thyroid gland , and parotid glands . rcc metastases to the nose and paranasal sinuses are the most frequently affected areas , followed by the tongue [ 1 , 3 , 9 , 11 , 12 ] . the most common presenting symptoms to the head and neck region include an enlarging neck mass , epistaxis , anosmia , facial pain , nasal obstruction , and diplopia . rcc is comprised of hypervascular tumors associated with multiple arteriovenous shunts due to the release of vascular endothelial growth factor as well as other angiogenic factors . given the fact that the kidneys receive 25% of the circulating blood volume , rcc has a high spreading potential via the blood [ 12 , 13 ] . rcc has 5 distinct histologic presentations : clear cell / conventional ( 75% ) , papillary ( 15% ) , chromophobe ( 5% ) , collecting duct ( 2% ) , and unclassified ( 3% ) . histopathologically , clear cell rcc typically shows a compact alveolar or solid architecture with varying degrees of cystic changes . rcc characteristically tends to exhibit numerous capillaries and thin - walled blood vessels in the supporting stroma . the cytoplasm is rich in lipids and glycogen ; the latter 2 elements dissolve during processing to provide the characteristic clear cytoplasm [ 2 , 7 ] . immunohistochemical staining helps in this distinction , exhibiting focal cytokeratin positivity ( vs. minor salivary gland cancers that show diffuse positivity ) and a strong reaction for vimentin . radiologic diagnosis is based on the vascular nature of the tumor , which shows moderate to marked signal enhancement on contrast ct . if contrast enhancement indicates destruction and lack of tumor calcification , metastatic rcc should be part of the differential diagnosis . excision is usually performed to control pain and to manage any potential complications from space - occupying masses in the head and neck region , including the brain [ 1 , 10 ] . rcc does not respond well to radiation therapy , and while chemotherapy ( interleukin-2 , interferon- , and 5-fluorouracil ) may be useful in cases of residual disease after resection , a positive response is experienced in less than 25% of patients . radiotherapy can only improve symptomatic relief and increase quality of life for perhaps a few months . the 5-year survival rate for rcc after nephrectomy is 6075% . excision of solitary metastatic lesions of rcc following nephrectomy results in a survival rate of 41% at 2 years and 13% at 5 years . the prognosis for patients with multiple rcc metastases is poor , with a 5-year survival rate of 07% [ 2 , 4 , 9 , 14 ] . we report on a 62-year - old male who presented to the ophthalmology service with vi cranial nerve bilateral paresis , absence of pharyngeal reflex , dysarthria , right tongue deviation , and paralysis to the right side of the face . ct and mri were performed , with ct showing a large expansive process at the cranial base with clivus and right petrous apex osteolysis ( fig . an mri t1 sequence showed a solid isointense expansive process with bilateral internal carotid artery involvement ( fig . 3 ) . an mri t2 sequence revealed small hyperintense areas indicative of being cystic in nature or suggestive of central necrosis ( fig . ipsilateral side secretions coming from the eustachian tube indicated the mastoid region had been compromised . an additional mri t1 sequence following administration of gadolinium contrast material showed moderate enhancement with clear involvement of bilateral internal carotid arteries ( fig . 5 ) and the cavernous sinus , posterior ethmoidal sinus , clivus and both petrous apex infiltration . the head and neck cancer committee recommended ultrasonography , which subsequently revealed a heterogeneous echogenic multilobular mass on the right kidney , with irregular contours ( fig . pelvic and abdominal ct was performed , revealing a large mass on the right kidney with irregular contours and poor definition . further investigations performed following contrast injection revealed a heterogeneous density with a hypodense central area and some calcifications in thickness ( hyperdense deposits in the body of the primary tumor : right kidney ) ( fig . radiotherapy was recommended , but due to the advanced stage of the disease the patient was enrolled in a palliative care and pain control program . metastases of malignances in the head and neck are rare . when present , they tend to be very aggressive due to the advance stage of the disease . multidisciplinary management , clinical experience and high - resolution imaging support are crucial for determining tumor identification , primary tumor localization , and the extent of tumor involvement .

we report on a patient who presented with cranial nerve vi bilateral paresis , absence of pharyngeal reflex , dysarthria , right tongue deviation , and right facial paralysis . imaging studies showed an expansive process in the cranial base with clivus and petrous apex osteolysis . a biopsy confirmed the presence of clear cell adenocarcinoma and suspicion of renal tumor metastases . abdominal imaging studies revealed a mass in the right kidney . consequently , radiotherapy was performed , and the patient was enrolled in a palliative care and pain control program .

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limited mouth opening is a common health problem that interferes with eating , speech and oral hygiene . the causes of limited mouth opening include trauma , infection , temporomandibular joint disorders ( tmds ) , neurological disorders , rheumatoid arthritis , drugs , tumors , hyperplasia of the coronoid process , etc . this condition can interfere with various medical treatments that require access to the oral cavity . masticatory muscle tendon - aponeurosis hyperplasia ( mmtah ) , a rare cause of limited mouth opening , is a new disease entity which has been recently established [ 24 ] . at present , most clinicians are not yet aware of this disease , leading to the risk of misdiagnosis as other diseases , such as masseter muscle hypertrophy and tmds . in february 2013 , a 39-year - old woman presented with limited mouth opening suspected by her dentist to be caused by tmd . she could not open her mouth widely since her elementary school days , and restricted mouth opening gradually developed . oral examination revealed no pain on motion , tenderness , clicking or injury of the temporomandibular joint . the lower jaw moved smoothly , but unaided maximal mouth opening was only 27 mm ( supplementary video 1 ) . thick aponeurosis of the anterior aspect of the masseter muscle was noted bilaterally ( fig . 1 ) . on maximal mouth opening , intraoral palpation along the anterior border of the masseter muscle confirmed a hard cord - like structure , consistent with the findings on mri . thick masseter muscle aponeurosis and coronoidectomy , performed under general anesthesia , increased maximal mouth opening from 29 to 53 mm . although the coronoid process did not interfere with the zygomatic bone on mouth opening , the coronoidectomy was needed to completely resect the temporal muscle tendon from the posterior of the coronoid process . mmtah was designated as a new disease entity by the japanese society for oral and maxillofacial surgeons in 2005 . however , most clinicians throughout the world are probably unaware of the existence of mmtah , potentially leading to misdiagnoses such as tmd . for example , resection of a portion of the masseter muscle was previously reported not to improve limited mouth opening in a patient with bilateral masseter muscle hypertrophy . although both mmtah and masseter muscle hypertrophy present with muscle hypertrophy , these two diseases differ substantially because masseter muscle hypertrophy is not accompanied by limited mouth opening . the aforementioned case is thus suspected to be mmtah . a diagnosis of typical mmtah requires bilateral thick aponeuroses on the anterior aspect of the masseter muscle as confirmed by intraoral palpation and mri , as well as slowly progressing limited mouth opening , which often develops in childhood . mmtah is frequently accompanied by a square mandibular configuration with mandibular angle hypertrophy due to the hyperplastic aponeurosis and tendon . the limited mouth opening associated with mmtah is due to extension disturbance of the muscles , resulting from hyperplasia of tendons and aponeuroses , which appear normal histopathologically . we have performed the procedure described above followed by mouth - opening training in 34 patients since 2000 . the ratio of mmtah among about 1000 persons in japanese elementary and junior high schools was 1% ( unpublished data ) . anesthesiologists have also reported problems in laryngoscopy during the induction of anesthesia in patients undergoing surgery for mmtah . recently , lehman et al . reported that four female patients who had presented with limited mouth opening and lateral and protrusive movements within normal limits had been treated by bilateral coronoidectomy with the significant improvement of limited mouth opening . . when clinicians notice limited mouth opening on oral examination , they should be knowledgeable about diseases associated with limited mouth opening and a square mandibular configuration , such as mmtah .

most clinicians throughout the world are probably unaware of the existence of masticatory muscle tendon - aponeurosis hyperplasia ( mmtah ) , potentially leading to misdiagnoses such as temporomandibular joint disorder ( tmd ) . here , we introduce this disease from the viewpoint of education . in february 2013 , a 39-year - old woman presented with limited mouth opening . her facial configuration was characterized by a square mandible . there was no evidence of tmd . magnetic resonance imaging ( mri ) showed bilateral enlargement of the masseter muscles . additionally , a thick aponeurosis of the anterior aspect of the masseter muscle was noted bilaterally . on maximal mouth opening , intraoral palpation along the anterior border of the masseter muscle confirmed a hard cord - like structure , consistent with the findings on mri . mmtah was diagnosed . when clinicians notice limited mouth opening on oral examination , they should be knowledgeable about diseases associated with limited mouth opening and a square mandibular configuration , such as mmtah .

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garcin s syndrome was first defined in 1926 by raymond garcin , who defined the syndrome paralytique unilateral global des nerfs craniens ( 1 ) . garcin s syndrome is characterized by ( 1 ) : ( i)the presence of unilateral palsies of the cranial nerves,(ii)no sensory or motor long tract disturbance,(iii)no intracranial hypertension and(iv)an osteoclastic lesion in the skull base the presence of unilateral palsies of the cranial nerves , no sensory or motor long tract disturbance , no intracranial hypertension and an osteoclastic lesion in the skull base patients reported to have garcin s syndrome do not always have unilateral palsies of all cranial nerves ; thus , this syndrome was redefined as the presence of at least seven ipsilateral cranial nerve palsies . he noticed a mass in his left buccal sulcus , and both his general medical practitioner and general dental practitioner prescribed a total of three courses antibiotics . as there was no resolution he was referred to his local oral and maxillofacial unit for further investigation . by this time he was also complaining of left sided deafness and diplopia . on extra - oral examination he had an obvious soft tissue swelling emanating from his parotid , and extending buccally towards the mental foramen . an orthopantomogram showed a widening of the inferior dental nerve canal and signs of bony resorption . left acoustic ( viii ) and facial ( vii ) cranial nerve palsies occurred initially , followed by trigeminal ( v ) , abducens ( vi ) glossopharyngeal ( xi ) , vagal ( x ) , accessory ( xi ) , and hypoglossal ( xii ) left sided cranial nerve palsies . seven of the 12 cranial nerves were involved in this patient . nevertheless , his muscle tone , power , sensation , and coordination were normal in all four extremities . gadolinium - enhanced mri of the brain showed an extra - axial enhancing lesion , which enveloped the hemi - mandible at the level of the left inferior alveolar nerve . the lesion was 3.8 cm at its maximal thickness , and eroded the cortex and the mandible . this revealed a left sided parotid mass extending posteriorly to the mandibular angle , anteriorly beyond the mental foramen and postero - superiorly to the skull base . an incisional biopsy was taken which was histologically reported as non - hodgkin s lymphoma . following discussion at the head and neck mdt , the patient was referred to the lymphoma team . a rare case of garcin s syndrome presented with progressive multiple unilateral cranial nerve palsies due to non - hodgkin s lymphoma . to our knowledge , only one case of garcin s syndrome due to non - hodgkin s lymphoma has been previously reported . ( 3 ) it is more frequently caused by malignant disease ; however it can be caused by benign disease . garcin s syndrome is reported widely as a result of metastatic spread from a primary tumour . there are only three cases of garcin s syndrome being caused by a primary lesion within the head and neck reported within the last forty years . these were caused by a chemodectoma ( 4 ) and a meningioma ( 5 ) . benign causes of garcin s syndrome include pachymeningitis secondary to otitis media ( 6 ) and a large internal carotid artery aneurysm ( 7).our case is interesting as it was caused both by a primary lesion , and it is the only non - hodgkin s lymphoma case to have been found pre - mortem and as a primary lesion intra orally . on admission to our hospital , the patient had palsies of seven left cranial nerves , which satisfied the clinical picture of garcin s syndrome . the initial diagnosis in this case was bell s palsy which is frequently encountered in clinical practice . multiple cranial nerve palsies are rare ; however the clinician must be aware of such cases to make sure early accurate diagnosis is achieved . in conclusion , multiple cranial palsies are rare and often present initially as a single cranial nerve palsy . in our case of garcin s syndrome the patient presented with a facial nerve palsy and an accurate diagnosis of non - hodgkins lymphoma at this stage may have prevented the development of this syndrome . the diagnosis can only be a made with a high clinical suspicion and appropriate diagnostic imaging .

an 80 year old man presented with a twelve month history of progressive multiple unilateral cranial nerve palsies . a gadolinium enhanced mri scan of his head and neck was performed . this showed an extra - axial enhancing lesion , which enveloped the hemi - mandible at the level of the left inferior alveolar nerve , and a dumbbell shaped lesion within the cerebellopontine angle . an incisional biopsy was performed to gain a tissue diagnosis , which demonstrated a non - hodgkin s lymphoma . the combination of signs , symptoms and radiological findings enabled a diagnosis of garcin s syndrome secondary to non - hodgkin s lymphoma .

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strains in this study were jm837 ( leu132 h- ) , jm1262 ( pil1-mcherry::natr h- ) , jm1293 ( fhn1::kanmx6 ura4-d18 leu132 ade6-m210 h ) and jm1461 ( sle1::kanmx6 ura4-d18 leu132 ade6-m210 h ) . expression from plasmid pjm512 ( prep41-pil1-gfp ) was induced by growth in the absence of thiamine for 36 hours at 32c . to observe endogenous pil1-mcherry rods , strain jm1262 was grown on ye4s plates at 32c for 3 d. cells were scraped from the plate and immediately imaged . electron microscopy : for thin sectioning , cells carrying plasmid pjm512 ( prep41-pil1-gfp ) or control plasmid pjm211 ( prep41-gfp ) were grown in the absence of thiamine for 36 hours at 32c , and then prepared and imaged as previously described . for immunolabeling of pil1 bundles , fixations and digestion were the same except for the following changes : initial fixation of 3% pfa/1% gta was used instead of 3% gta/1% pfa . samples were incubated in 0.05 m glycine in nacac buffer for 30 min to remove excess aldehydes . additionally , 1% p - phenylenediamine ( ppd ) was included in each etoh solution . four additional 85% etoh/1% ppd rinses over 1 hour were performed , and then pellets were resuspended in a 2:1 mixture of 85% etoh/1% ppd : lr white medium resin . this suspension was placed on a rotator for 2 hours at room temperature and then resuspended in 1:1 85% etoh/1% ppd : lr white medium resin , rotated for 1 hour , and then kept at 4c overnight . the following day , samples were resuspended in 1:2 85% etoh/ 1% ppd : lr white medium resin rotated for 1 hour at room temperature and then resuspended in 100% lr white medium resin . solution was changed until clear , and then 3 more changes over 6 hours rotating at room temperature were performed before placing at 4c overnight . samples were warmed to room temperature and 4 changes of 100% lr white medium resin were made with 1 hour each change . samples were transferred to gelatin capsules and left for 4 h at room temperature , then polymerized at 50c for 24 h. thin sections ( 7080 nm ) were placed on g300 nickel - coated grids ( electron microscopy sciences ) . grids with sections were washed in pbs for 5 min , put in block solution of pbs + 5% bsa ( sigma - aldrich ) for 15 min , incubated for 1 hour in 1/25th dilution of rabbit anti - gfp , washed 6 times for 2 min , incubated for 30 min in a 1/25th dilution of goat anti rabbit 6 nm gold - conjugated secondary antibody ( 25104 ; electron microscopy sciences ) , then washed 6 times for 2 min with 2 additional washes in pbs and 2 final washes in distilled water . washes and antibody dilutions were in pbs + 0.1% bsa ( sigma - aldrich ) at rt . grids were stored at room temperature and stained with 2% aqueous uranyl acetate for 4 min and reynold 's lead citrate for 10 sec . light microscopy : fluorescence microscopy was performed as previously described using a deltavision imaging system ( applied precision ) . for filipin staining , cells expression from plasmid pjm512 was induced by growth in the absence of thiamine for 20 hours at 32c ; filipin ( sigma f9765 ) was added at a final concentration of 5 g / ml to live cells . this work was funded by national institutes of health grant gm099774 ( to j.b.m . ) and t32-gm008704 ( to r.k . ) .

cytoskeletal polymers are organized into a wide variety of higher - order structures in cells . the yeast bar domain protein pil1 self - assembles into tubules in vitro , and forms linear polymers at cortical eisosomes in cells . in the fission yeast s. pombe , over - expressed pil1 forms thick rods that detach from the plasma membrane . in this study , we used thin - section electron microscopy to determine the ultrastructure of these cytoplasmic pil1 rods . we found that cytoplasmic rods contained crosslinked pil1 tubules that displayed regular , hexagonal spacing . these bundles were stained by filipin , a sterol - binding fluorescent dye , suggesting that they contained lipids . cytoplasmic pil1 rods were present but less abundant in sle1 and fhn1 mutant cells . we also found that endogenous pil1 formed thick rods under saturated growth conditions . taken together , our findings suggest the presence of cellular mechanisms that assemble pil1 tubules into higher - order structures .

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it is seen with the use of lasers that do not make use of optical fibers for laser beam delivery , such as carbon - dioxide ( co2 ) lasers which use articulated arm technology . they have optical fibers for delivery of the laser at the site of surgery , facilitating more precision and control . a 7-year - old boy was admitted for excision of a cystic swelling at the posterior aspect of the base of the tongue a few centimeters anterior to the valleculae . the smallest laser endotracheal tube ( ett ) available was of 7-mm outer diameter ( od ) and an internal diameter of 5.5 mm . after induction of anesthesia with propofol , followed by administration of suxamethonium intravenously ( iv ) , nasotracheal intubation was done with this tube . anesthesia was maintained oxygen in air , atracurium , intermittent boluses of propofol , and fentanyl iv . the saline - soaked throat pack was obstructing the field of vision of the surgeon and also restricting the outward pull of the tongue as cyst was large ( 3 3 cm ) and placed posteriorly . the surgeon assured that adequate precautions would be taken to avoid bringing the diode laser delivery handle tip in contact with the ett . toward the end of the surgical laser excision , the tip of the handle accidently slipped and touched the ett . we heard a very short pop like noise which lasted for about 12 s. the exhaled gas from the expiratory valve also smelt of smoke for about a minute or so . there was however no change in hemodynamics , drop in spo2 or reduction in air entry / chest expansion . as the surgery had been completed and we were able to ventilate the lungs , we reversed the neuromuscular blockade . after tracheal extubation , a flexible laryngopharyngoscope was passed to visualize the trachea up to the carina and fortunately everything appeared to be normal . the removed ett [ figure 1 ] had a very small circular hole and the inner aspect of the tube was black distal to the hole [ figure 2 ] . the cuff was intact but the tubing from the pilot balloon to the cuff was damaged , which is typically seen in patient recovered well and was shifted to postoperative , ward , monitored and given humidified oxygen and discharged next day . diode lasers are used with low power setting and do not usually cause perforation or damage to polyvinyl chloride ( pvc ) ett coming in direct contact . though studies have shown silicon and red rubber tubes to be more resistant to ignition compared to pvc , some studies have reported that pvc is less flammable than silicon or red rubber , having a flammability index of 0.26 vs. 0.19 for silicon and red rubber , respectively . use of laser resistant material wrapped around pvc ett or double - cuffed silicon - coated ett is however more safe . laser - resistant ett are bulkier and more rigid than conventional ett and thus need careful insertion to prevent mucosal abrasions . in the event of a blow - torch phenomenon , pvc tubes burn more vigorously and hydrochloric acid may be produced , which is a pulmonary toxin . in case of such an airway fire , oxygen should be temporary discontinued , damaged ett removed , trachea reintubated with a fresh ett , and the pharynx flushed with cold saline . a rigid or fiberoptic bronchoscopy examination should be done to look for damage and pieces of burned ett . humidified oxygen , steroids , and antibiotics must be administered and at times controlled ventilation and tracheostomy may become necessary . postoperatively , patient should be intensively monitored and a chest x - ray should be taken . surgeons must ensure that laser energy is not reflected from smooth metal surfaces or directed at sensitive structures . applying protective metal foil wraps to ett , such as aluminum or copper has been advocated.[35 ] the ett cuff can be filled with colored saline and placed far distally in trachea and the visible cuff covered with moistened cotton pledgets , which should be remoistened as needed . laser resistant tubes are available for use during laser surgery . to reduce the obstruction in the surgical field , by airway instruments ,

we report a case of blow - torch phenomenon encountered during diode laser assisted excision of a thyroglossal cyst in a child . this is first such case report from india and highlights an unusual complication which anesthesiologists need to be aware of due to the increasing use of operative laser .

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sarcomas are mesenchymal neoplasms with various lines of differentiation , i.e. , fibrocytic , myogenic , neurogenic , vascular , chondro - osseus , or undefined . it is a spindle - cell tumor composed of collagen - rich and myxoid parts . lgfs prefers subfascial soft tissue layers on the trunk and proximal extremities in younger adults but can also develop in internal organs . pediatric cases have also been reported.[13 ] herein , we present a 48-year - old female patient who developed a lgfs on the lower leg . the clinical presentation , histopathology , surgical treatment , and follow - up are discussed . a 48-year - old woman was referred to our department because she had developed a slow - growing plaque below the left knee for 2 years . on examination we found an otherwise healthy , slim , woman with a symptomless firm subcutaneous plaque of about 2 cm size on the anterior aspect of the left lower leg figure 1.there was some bluish discoloration and circumscribed ulceration but no erythema or warmth . ( a ) overview and ( b ) the ulcerated honeycomb - like plaque routine laboratory tests were unremarkable . thoracic dual - energy x - ray and abdominal and lymph node ultrasound excluded a metastatic spread . histology revealed a spindle - cell tumor , with mild atypia and fibroblast - like morphology [ figure 2 ] . cells were arranged in a whorled or plexifiorm pattern , with alternating collagenous stroma and myxoid zones . the tumor was surgically removed with a wide safety margin ( > 3 cm ) . the defect was covered by a mesh graft transplant covered by vacuum - assisted closure ( vac ; kci international ) [ figure 3 ] . compression stockings were prescribed to protect the transplant and prevent leg edema . a regular follow - up for at least 5 years ( a ) overview ( h&e , 4 ) and ( b ) detail ( h&e , 40 ) surgical procedure . ( a ) wide excision of suprafascial soft tissue ; ( b ) mesh graft transplantation ; and ( c ) placement of microporous white sponge for vacuum - assisted closure above the transplant lgfs is a very rare and distinctive type of fibrosarcoma that was first described by evans in 1987 . there is a discrepancy between the bland histologic features with sparse mitotic figures and absent or mild nuclear and cellular pleomorphism and the anaplasia . the hyalinizing spindle - cell tumor with giant rosettes is considered a subtype of lgfs.[13 ] the tumor is further characterized by t(7;16)(q34;p11 ) translocation and fusion of fus and creb3l1 genes . tumor cell phenotype is positive for vimentin , ema , cd99 , and bcl-2 , but negative for cd34 , sma , s-100 , desmin , keratins , neuron - specific enolase , and cd177 . the differential diagnosis includes other types of sarcomas , myxoma , neurofibroma , peripheral sheath tumor , histocytoma , desmoid tumor , and others . the diagnosis often is delayed - mainly because the patients do not seek treatment early . ( 2000 ) reported that in 15% of patients a histologic diagnosis was delayed by > 5 years . in our case although the histopathologic features suggest a low - grade malignancy , local recurrence is seen in more than 50% of patients and metastasis occurs in 6% of patients . tumor cell dormancy is responsible for very late metastasis in some patients , with 45 years being the longest period observed between primary surgery and metastasis . complete surgery with wide margins ( > 3 cm ) is the most important procedure . we used a combination of mesh graft transplantation and vacuum - assisted closure to cover the large defect . it has been demonstrated recently that such a combination , with microporous sponge for vacuum - assisted closure , results in a significantly improved take rate .

a 48-year - old female with an atypical plaque - like lesion of the lower leg is presented in this article . histologic investigation revealed a rare low - grade fibromyxoid sarcoma ( pt1a cn0 cm0 ; stage ia ) of suprafascial localization . staging of the patient did not reveal metastatic spread . the tumor was surgically removed with wide safety margins . the defect was closed using a mesh graft transplant and vacuum - assisted closure . healing was complete . regular follow - up for at least 5 years is recommended . besides the rareness of this tumor , this case is also remarkable because of the localization on the lower leg and the suprafascial soft tissue .

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left - sided inferior vena cava ( ivc ) is an unusual abnormality that may be clinically significant during renal surgery . we report the unique case of a patient with a centrally located left renal mass who underwent laparoscopic radical nephrectomy . during the hilar dissection the patient was noted to have a left - sided inferior vena cava with multiple renal veins and anomalous tributaries . the embryology of a left - sided inferior vena cava is reviewed , and the safety and feasibility of a laparoscopic approach is discussed . unexpected vascular anomalies may increase the risk of hemorrhage and necessitate conversion to open nephrectomy . we report the case of a major inferior vena cava ( ivc ) anomaly encountered during laparoscopic nephrectomy and discuss its embryogenesis and management . computed tomography revealed a 4-cm enhancing lesion located centrally within the left kidney ( figure 1 ) . laparoscopic left radical nephrectomy was planned and upon hilar dissection , the ivc was encountered without visualization of the aorta , confirming its left - sided orientation . in addition , 3 renal veins were noted , as was a left gonadal vein that drained directly into the ivc ( figure 2 ) . an aberrant vein was exposed that bridged the gonadal vein and the most caudal of the supernumerary renal veins . prior to dissection of the renal artery , the caudal renal vein , gonadal vein , and bridging anomalous vein were ligated and transected . abdominal ct scan illustrates the ivc as it courses from the normal anatomic position to the left - sided position : ( a ) ivc in right - sided anatomical position ( thick arrow ) ; ( b ) ivc crossing anterior to the aorta ( thick arrow ) ; ( c ) ivc crossing anterior to the aorta ( thick arrow ) and main left renal vein ( thin arrow ) . left renal mass is noted in a central location ; ( d ) ivc in left - sided position ( thick arrow ) and second left renal vein ( thin arrow ) . view of cephalad ( left ) and caudad ( right ) aspect of ivc ; kidney ( out of frame ) is located towards top of image . left gonadal vein drains into the left - sided ivc . two of the 3 left renal veins are noted . bridging vein between the main renal vein and gonadal vein is noted . the laparoscopic approach has become an accepted standard for extirpative renal surgery , with less postoperative pain , decreased hospital stay , and shorter convalescence compared with that of open surgery . colombo et al reported that hemorrhage continues to be the most common intraoperative complication of laparoscopic surgery , occurring at a rate of 2.3% and requiring open conversion in 0.9% of cases . preoperative knowledge of pertinent vascular anatomy is essential during laparoscopic renal surgery to avoid potential complications . to our knowledge , this is among the initial reported cases of a left - sided inferior vena cava encountered during laparoscopic radical nephrectomy . left - sided ivc is an abnormality that occurs at a prevalence of 0.2% to 0.5% and is usually asymptomatic . although commonly an incidental finding , it becomes clinically significant when it is mistaken for paraaortic lymphadenopathy or the main renal vein . the embryonic development of ivc involves the emergence and selective regression of 3 pairs of embryonic veins : the posterior cardinal , subcardinal , and supracardinal veins . anomalies of the postrenal segment of the ivc include retrocaval ureter , duplicated ivc , and left - sided ivc . a left - sided ivc is caused by persistence of the left supracardinal vein with regression of the right supracardinal vein . the left subrenal ivc then joins the left renal vein and crosses anterior to the aorta where it unites with the right renal vein . as a result , renal venous development results from anastomosis of the subcardinal and supracardinal veins . during normal development , multiple persisting renal veins is the most common anomaly of the venous developmental system with a prevalence ranging from 9% to 20% . the main clinical significance of this finding is the risk of iatrogenic injury during renal surgery . when a left - sided ivc is encountered , the surgeon must be suspicious of other anomalies . in our patient , 3 renal veins , careful examination of preoperative radiographic imaging is mandatory in the diagnosis of a left - sided ivc . case reports have described this phenomenon during laparoscopic live donor nephrectomy without adverse effects . in our experience , this anomaly may be more readily apparent when evaluating patients with higher resolution imaging . in accordance with other reports , our case demonstrates that laparoscopic radical nephrectomy can be successfully performed without complications in the presence of a left - sided ivc .

background : left - sided inferior vena cava ( ivc ) is an unusual abnormality that may be clinically significant during renal surgery.methods:we report the unique case of a patient with a centrally located left renal mass who underwent laparoscopic radical nephrectomy . during the hilar dissection , unusual vascular anatomy was encountered . the patient was noted to have a left - sided inferior vena cava with multiple renal veins and anomalous tributaries . laparoscopic radical nephrectomy was performed without complication.discussion:the embryology of a left - sided inferior vena cava is reviewed , and the safety and feasibility of a laparoscopic approach is discussed .

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healthcare is provided by public and private hospitals , and there are 5 major burns units . in january 2005 , pustular lesions were observed on the foot of a patient in 1 of the burns units , and similar lesions subsequently appeared on other patients . local health authorities were informed of the outbreak , and an investigatory team confirmed reports of similar infections in the city s other burns units , with retrospective identification of at least 19 probable cases occurring over a 5-month period . most patients had a fever ( 39.0c40.5c ) for 23 days , followed by the appearance of an eruption(s ) . lesions were typically small , rounded , umbilicated , and nodular in appearance with an erythematous base ( figure 1a ) . they contained cheesy pustular material and increased in size ( from 12 mm to > 1 cm in diameter ) and severity over 78 days . the lesions involved burn wounds and intact skin surrounding them , with the unhealed margins of the wounds being covered by a layer of thick yellow secretion . some patients had a sparse rash ; others had closely spaced lesions that produced a cobblestone appearance . a single lesion developed on a paramedical staff member s finger , and lesions developed around 1 patient s insertion site for an intravenous line ( figure 1b ) . in all instances , the disease was self limiting , and patients recovered in 34 weeks . c ) orthopoxvirus particles detected by electron microscopy ( em ) examination of negatively stained grids prepared from pustular material ( magnification 73,000 ) . d ) transmission em examination of ultrathin sections of infected vero cell cultures showing classic intracytoplasmic orthopoxvirus factories and maturing virus particles ( magnification 21,000 ) . results of bacteriologic and mycologic examination of biopsy samples , impression smears , and swab samples from lesions were negative . histopathologic examination showed extensive ulceration and granulation , with epidermal necrosis and subepidermal edema plus acute and chronic inflammatory cell infiltration . impression smears and biopsy tissues were sent to the special pathogens unit , national institute for communicable diseases ( nicd ) , sandringham , south africa , and to the health protection agency ( hpa ) , centre for emergency preparedness and response , porton down , salisbury , united kingdom . electron microscopy of negative - stained grids prepared at hpa and ncid laboratories from pustular material showed orthopoxvirus particles , and examination of ultrathin sections prepared from infected vero cell cultures at hpa found classic orthopox intracytoplasmic virus factories and particle maturation sites ( figure 1c , d ) . pcr was performed on nucleic acid extracted from the samples , using primers specific for regions of the orthopoxvirus hemagglutinin gene ( at nicd ) and b5r membrane protein gene ( at hpa ) . after nucleotide sequences were determined for the pcr products , phylogenetic analyses were conducted in relation to corresponding orthopoxvirus sequences obtained from genbank , using methods described elsewhere ( 14,15 ) . the causative agent was found to cluster with buffalopoxvirus isolates within the vaccinia subgroup of orthopoxviruses ( figure 2 ) , and 3 patients from 2 separate burns units were shown to be infected with the identical virus , which was distinct from other known buffalopoxvirus isolates . to investigate the possibility of a shared source of infection , 17 samples of saline , antimicrobial drug ointments , petroleum jelly , cotton dressings , and swabs in common use were obtained from the 5 burns units and tested by pcr at nicd ; no results were positive . inquiries led to the suggestion that the outbreak was probably propagated by transfer of infected patients between burns units . this hypothesis was confirmed when a policy to isolate all new admissions , including referrals from other burn centers , for their first 2 weeks in a unit successfully controlled transmission of new endogenous cases . maximum likelihood phylogenetic tree based on a 955-nt alignment of the karachi isolate and 33 orthopoxvirus sequences of the b5r gene from genbank constructed with clustalw ( www.ebi.ac.uk/clustalw/index.html ) and tree - puzzle ( http://bioweb.pasteur.fr/seqanal/interfaces/puzzle.html ) ; figures at nodes represent puzzle support values . the orthopoxvirus types are indicated to the right . control measures included education of staff , single - room or cohort isolation of patients infected or suspected of being infected with buffalopoxvirus , and reinforcement of infection - control practices , such as hand disinfection after contact with any patient . to reduce virus load in the environment , the measures proved effective in reducing transmission within burns units , but they did not prevent the sporadic arrival of newly infected patients . buffalopoxvirus outbreaks reported to date have been geographically restricted , and human cases have been limited to persons with direct exposure to infected animals , usually in rural communities ( 111 ) . this reported outbreak uniquely involved nosocomial infections in 5 widely separated burns units in karachi , pakistan . however , buffaloes are the most common dairy animal in pakistan , even within the city limits of karachi , and buffalo fat , particularly in the form of butter or ghee , sometimes is used at home as a dressing for burns . thus , burn patients newly infected with buffalopoxvirus due to disparity in the sophistication and cost of the care provided at the burns units in karachi , patients are often transferred or move themselves between units , thus facilitating the possible spread of infection . in this outbreak , 6 of the 19 patients with putative cases of buffalopoxvirus infection are known to have transferred between burns units during treatment . the infection was of low virulence for humans . delay in recognizing and investigating the outbreak is cause for concern and can be ascribed to poor awareness and lack of resources .

during 5 months in 20042005 , buffalopoxvirus infection , confirmed by virus isolation and limited nucleic acid sequencing , spread between 5 burns units in karachi , pakistan . the outbreak was related to movement of patients between units . control measures reduced transmission , but sporadic cases continued due to the admission of new patients with community - acquired infections .

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consecutive outpatients were recruited at 2 primary healthcare centers and hospitalized patients at a governmental referral center ( dr . all eligible auf patients ( > 5 years of age ) were included who met the following criteria : fever > 38c ( central ) for < 14 days with no apparent other disease . the study was approved by the local medical ethical committee . a specific microimmunofluorescent antibody ( ifa ) assay for rickettsia spp . was performed in marseille , france , by using whole - cell antigens of o. tsutsugamushi , r. japonica , r. heilongjiangensis , r. slovaca , r. honei , r. conorii subsp . indica , rickettsia ati , r. helvetica , r. felis , r. typhi , and r. prowazekii . the assay results were considered positive when 1 ) antibody titers were > 256 for immunoglobulin ( ig ) g and > 64 for igm , or 2 ) seroconversion was observed , or 3 ) a > 4-fold increase in titers between the acute - phase and the convalescent - phase serum specimen was detected . convalescent - phase samples were screened with the leptotek dri dot ( biomrieux , marcy letoile , france ) . all positive samples were tested by the microscopic agglutination test ( mat ) and igg elisa ( 8) . additionally , a real - time pcr specifically targeting the secy gene of pathogenic leptospira spp . , a panel of 31 serovars was used containing 28 pathogenic and 3 nonpathogenic serovars . for patient samples tested by elisa or mat , a titer > 320 on a single sample was considered positive ; also considered positive were those samples that showed seroconversion or a > 4-fold increase in titers between paired samples , as well as any patient sample with a positive pcr , irrespective of the serologic result . the main symptoms were headache ( 85% ) , myalgia ( 70% ) , nausea ( 64% ) , cough ( 44% ) , and abdominal pain ( 38% ) . murine typhus and leptospirosis were found to cause auf in this clinical series ( appendix table ) . in total , 9 patients ( 7% ) had evidence of an acute infection with r. typhi ; none showed a rash . murine typhus could be diagnosed in 6 ( 9% ) of 67 hospitalized patients ; 3 ( 4% ) of 70 outpatients had acute murine typhus . one patient showed evidence of a past infection with r. typhi ( ifa igg / igm titer 128/0 in both serum specimens ) . leptospirosis was diagnosed in 13 ( 10% ) of 137 patients ; results for 2 of these patients were positive only by pcr . eleven leptospirosis patients were recruited in the hospital ; 2 patients were recruited outside the hospital . consequently , the percentage of auf caused by leptospirosis in hospitalized patients was 16% and in outpatients 3% . no dual infections were detected ; however , 3 ( 23% ) leptospirosis patients showed titers in the r. typhi ifa assay . we report that murine typhus and leptospirosis are important causes of auf in semarang , indonesia . a previous study from rural thailand identified both diseases in 2.8% and 36.9% of auf cases , respectively ( 6,7 ) . in vientiane , the capital of laos , r. typhi was reported to cause fever in 9.6% of investigated persons , results that closely resembling our data ( 10 ) . unfortunately , leptospirosis was not investigated . in the present study , we expected leptospirosis to be a cause of auf because the dr . these cases were not included in the study because of the high clinical suspicion of leptospirosis on admission with jaundice , azotemia , and/or bleeding . a definite diagnosis of murine typhus and leptospirosis co - infections could not be made , but in 3 cases this scenario was plausible . we did not find evidence for scrub typhus , which we expected , because o. tsutsugamushi transmission occurs primarily in rural areas ( 11 ) . although sfgr have been reported in southeast asia and proof for their presence in indonesia is accumulating ( 2,12 ) , these rickettsia were not identified as a cause of auf in the present study . from an epidemiologic point of view , semarang , indonesia , seems to encompass environmental circumstances that are prerequisites for r. typhi and leptospirosis transmission . previous studies have shown that murine typhus is particularly prevalent in tropical port cities where rats are abundant ( 13,14 ) . in the indonesian urban situation , r. rattus and r. norvegicus rats are likely to be the main hosts harboring r. typhi infected x. cheopsis fleas ( 12,15 ) . these rats are also likely to be the maintenance hosts for pathogenic leptospira spp . in indonesia . although serologic analysis might be hampered by cross - reactions and test sensitivity issues , we believe that our data are representative for the area . the chosen cut - off values are unlikely to cause false - positive results in a disease - endemic setting . in regard to leptospirosis serologic analysis this panel included serovars recommended by the world health organization and serovars that were previously isolated in indonesia . moreover , most serogroups were represented in our panel , and cross - reactions are likely to detect missing serovars . because of nonspecific clinical features , both diseases are difficult to diagnose on clinical grounds only . therefore , rapid , cheap , and reliable diagnostic tests are needed to support clinical decision making . clinical and laboratory data of patients with rickettsioses and leptospirosis , indonesia , february 2005-february 2006 *

to investigate rickettsioses and leptospirosis among urban residents of semarang , indonesia , we tested the blood of 137 patients with fever . evidence of rickettsia typhi , the agent of murine typhus , was found in 9 patients . another 9 patients showed inconclusive serologic results . thirteen patients received a diagnosis of leptospirosis . no dual infections were detected .

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a 37-year - old male underwent endothelial keratoplasty in the right eye for primary graft failure following large diameter ( 11.5 mm ) therapeutic penetrating keratoplasty . the therapeutic penetrating keratoplasty was done for advanced fungal keratitis 6 months prior to dsaek . following therapeutic keratoplasty the graft was edematous with 10 intact sutures covered by conjunctiva , the anterior chamber was deep with few peripheral anterior synechiae , pupil showed posterior synechiae , and lens showed early nuclear sclerosis . considering the patient 's age and the absence of significant cataract , simultaneous cataract surgery was deferred . the posterior lamellar graft was inserted by the push - in technique using the sheet iol glide ( bd medical - ophthalmic systems , franklin lakes , nj usa ) protecting the endothelium with sodium hyaluronate 1% . the graft clarity recovered in 1 month after the surgery . at 3 months postoperative visit , pre - operative evaluation by confocal microscopy ( nidek , confoscan 4 ) revealed an endothelial count of 1937 cells / mm . biometry was performed using the keratometry readings obtained from orbscan ii ( bausch and lomb 's , florida , usa ) and iol power was calculated for a postoperative targeted refraction of 0.5 diopters of myopia . irrigation was kept off while inserting the phaco handpiece into the anterior chamber to avoid dislodging the graft . during surgery , a dispersive ophthalmic viscosurgical device ( hydroxypropyl methylcellulose 2% , viscomet , sun pharmaceuticals industries ltd . , on the first postoperative day , vision was 20/160 , improving to 20/80 , and the graft was compact [ figs . 1 and 2 ] . he was treated with ofloxacin 0.3% eyedrops 6 times / day for a week and prednisolone acetate 1% eyedrops 8 times / day for the initial 1 week , followed by tapering of one drop a week and finally maintained on 3 times / day . one month after the cataract surgery , his vision was 20/50 . at the last visit , 3 months later , the graft was compact and the best corrected visual acuity was 20/30 with a 0.75 d sph/1.50 d cyl at 160. table 1 shows the visual acuity , donor thickness [ assessed by anterior segment optical coherence tomography ( oct ) , visante : carl zeiss , germany ] and visual acuity pre- and post - cataract surgery . slit - lamp photograph of the right eye after dsaek ( day 1 post op ) post - op day 1 anterior segment oct image showing well - attached , compact graft pre and post - cataract surgery parameters endothelial cell density changes cataract surgery following penetrating keratoplasty is a safe and effective procedure , with a low but definite risk of corneal graft failure . however , the safety and efficacy of intraocular intervention in eyes that have undergone dsaek is not well established . post - dsaek surgical interventions may be fraught with the risk of endothelial cell damage or donor graft detachment or subsequent endothelial rejection . therefore , patients with visually significant cataract often undergo cataract surgery at the time of endothelial keratoplasty . it may be deferred in eyes where the anterior chamber can not be properly visualized . in eyes with crystalline lens or early nuclear sclerosis that have undergone only endothelial keratoplasty , cataract formation may be hastened due to surgical manipulation , air tamponade at the time of surgery and use of postoperative steroid medications . it is likely that all the mentioned factors might have led to accelerated cataract progression in this case . the specific surgery - related issues to be considered in these eyes are : the site of internal incision in relation to the edge of the lamellar graft , turbulence during insertion of the phaco handpiece with irrigation , which can potentially lead to graft dislodgement , reduced working space in the anterior chamber , and endothelial cell loss during surgery . an endothelial cell loss of 14.7% was noted at 3 months after dsaek and an additional loss of 19.3% was noted from the time of cataract surgery to 3 months later . the overall cell loss at 6 months post - dsaek was 31.2% , which is comparable to the endothelial cell density changes reported after dsaek in various series . this case shows that subsequent intraocular surgery with appropriate precautions can be performed safely in post - dsaek eyes . however , the long - term effect on the endothelium and graft survival needs to be better understood .

management of endothelial dysfunction in phakic patients is sometimes a dilemma for corneal surgeons . phakic patients with visually significant cataract and endothelial dysfunction are preferably managed by performing combined cataract surgery with endothelial keratoplasty . however , combined surgery may be deferred in eyes with early incipient cataract , younger age and where anterior chamber is poorly visualized . as cataract formation may be accelerated after endothelial keratoplasty , these eyes may need cataract surgery subsequently . surgical intervention in eyes with endothelial keratoplasty is of concern as this may affect the graft adversely and threaten graft survival . in this report , we describe the intraoperative surgical details and postoperative clinical course of a patient who underwent phacoemulsification with intraocular lens implantation after descemet stripping automated endothelial keratoplasty ( dsaek ) .

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in summary , we have developed a novel dna binding motif consisting of two dna binding fragments of natural tfs connected via an at - hook linker , which allows the selective recognition of designed , extended dna sequences ( up to 13 bp ) . the success of this design relies on the ability of the at - hook moiety to act as a bidentate minor groove - anchoring device that delivers the dna binding tf fragments to appropriate positions for insertion in their respective major grooves . the peptidic nature of the at - hook allowed an easy installation of each of the dna binding peptides at the c- and n - terminus of the anchor . the construct represents the first demonstration of an engineered synthetic dna binder that reaches two consecutive major grooves across the minor groove . the tripartite ( major minor major groove ) recognition introduces a novel dna binding motif that lacks a natural counterpart . this approach promises to be applicable to other dna binding tf fragments addressing different sites , and introduces a novel way of targeting specific and long dna sequences . electronic supplementary information ( esi ) available : peptide synthesis , full experimental procedures and analytical data of the peptides and products obtained .

we report the rational design of a dna - binding peptide construct composed of the dna - contacting regions of two transcription factors ( gcn4 and gaga ) linked through an at - hook dna anchor . the resulting chimera , which represents a new , non - natural dna binding motif , binds with high affinity and selectivity to a long composite sequence of 13 base pairs ( tcat - aatt - gagag ) .

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hemorrhage after percutaneous nephrolithotomy ( pcnl ) is a significant complication that occurs in a small percentage of cases . however , arterial injuries sometimes require transarterial embolization to control the refractory bleeding . in patient presenting with refractory bleeding , pseudoaneurysm formation is the most common cause with a reported incidence of 0.6 - 1% . we report a case of early erosion of an embolization coil from the renal vasculature into the urinary collecting system causing urinary tract obstruction and urosepsis . a 23-year - old male underwent left urs and pcnl for a left upper ureteric calculus and a 2.5-cm lower pole renal calculus in a community hospital in december , 2010 . one week after nephrostomy tube removal , the patient experienced gross hematuria with clot retention . the patient underwent endoscopic bladder clot evacuation and dj stent removal in the same hospital . two weeks later , again he developed gross hematuria with fever and a significant decrease in hematocrit . after resuscitation the patient was referred to our centre . on angiography , there was a pseudoaneurysm in the lower segmental renal artery . after 3 months of embolization , the patient presented with high - grade fever , left flank pain and burning micturiton . on x - ray kub 2 coils were seen in left renal area , whereas 1 coil was seen in l3 transverse process area . axial noncontrast and contrast - enhanced ct images showed left hydronephrosis with dilated upper ureter and an embolization coil in the upper ureter [ figure 1 ] . x ray kub shows 2 coils in left renal area , 1 coil in l3 transverse process area . ct urogram shows left hydronephrosis with dilated upper ureter and 2 coils in left kidney & 1 coil in upper ureter in 1975 , angioembolization for renal pseudoaneurysm was reported in a human patient when an autologous blood clot was used to embolize a bleeding pseudoaneurysm as a temporary measure before nephrectomy . we found only three case reports in which embolization coil migrated to the collecting system.[810 ] in all these case reports the coil eroded after 1 year following embolization . all the three patients presented with hematuria and renal colic . in our case , patient presented early ( 3 months ) with complaints of renal colic and persistent fever after coil embolization . hypothetically three mechanisms of coil erosion have been proposed . first , the diameter of arteriocaliceal communication might be larger than the embolization coil , and the coil gets extruded through the communication soon after placement . second , the arteriocaliceal communication could get dilated over time because of inflammation due to infection or the constant irritation from the indwelling coil itself , leading to eventual erosion into the collecting system . finally , rupture of the weakened wall of a pseudoaneurysm exposed to high arterial pressure may lead to erosion . according to the first hypothesis , if the arteriocaliceal communication was larger than the embolization coil than all three coils would have extruded through the communication and gross hematuria would have reappeared . the third mechanism would have lead to massive hematuria in addition to the coil migration . in this case the patient presented with high - grade fever and left flank pain but not hematuria . therefore in this case the second mechanism seems to be the most likely cause of erosion of the embolization coil . one of the important but rare causes of urinary tract obstruction is the migration of embolization coil into urinary collecting system .

refractory bleeding following percutaneous nephrolithotomy ( pcnl ) is mainly due to formation of pseudoaneurysm . transarterial embolization is required to control the bleeding in such cases . we report a case of post - pcnl hematuria in whom angioembolization was done . an early erosion of the embolization coil from the renal vasculature into the urinary collecting system occurred , causing urinary tract obstruction and urinary tract infection ( uti ) . the coil was retrieved ureteroscopically after control of uti with antibiotics . migration of embolization coil into urinary collecting system is a rare but important cause of urinary tract obstruction . the treating physician as well as the patient should be aware of this complication .

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potential candidates include l - lactate , -hydroxybutyrate , d - lactate , salicylate , formate and oxalate in toxicological situations , pyroglutamate , semisynthetic penicillins , sulphate and hippurate in renal failure , and occasionally urate and amino acids with catabolic states and total parenteral nutrition . reports of increased tricyclic acid ( tca ) cycle anions in shock are now emerging . their presence is often inferred from the anion gap ( ag ) , calculated as [ na ] + [ k ] - ( [ cl ] + [ hco3 ] ) . when its reference range is exceeded , a search for unmeasured anions should commence , irrespective of the overall metabolic acid - base status , because a competing metabolic alkalosis can mask their presence . likely culprits vary with the clinical scenario , but the search usually starts with l - lactate and -hydroxybutyrate . during this process , stoichiometry is tracked between ag ( measured ag normal ag ) and the summed concentrations of suspect anions ( always in meq / l , because we are dealing in electrical neutrality ) . if ag both sensitivity and specificity are reduced by perturbations of albumin ( remembering that albumin negative charge forms the bulk of the normal ag ) , ph , [ ca ] , [ mg ] and [ phosphate ] . the most promising alternative is the strong ion gap ( sig ) like the ag , the sig quantifies unmeasured anions minus unmeasured cations , but unlike its predecessor it is insulated from variations in [ albumin ] , [ phosphate ] , ph , [ l - lactate ] , [ ca ] and [ mg ] . in the previous issue of critical care , bruegger and colleagues combine sig calculations with capillary electrophoresis , and report that anions associated with the tca cycle , specifically citrate and acetate , contribute to the metabolic acidosis of canine haemorrhagic shock . their data originate from an earlier experiment designed to investigate the benefits of a perflurocarbon - based oxygen carrier during resuscitation from a predefined oxygen debt . capillary electrophoresis on specimens before shock , during shock and on resuscitation revealed maximal citrate elevations of 1.9 meq / l , whereas the peak acetate increase was 3.4 although these findings fuel ongoing speculation concerning tca anions in shock , several potential confounders are worthy of comment . during preparation , the animals acquired major metabolic perturbations , with severe baseline hypoalbuminaemia ( 1.5 g / dl ) and impressive hyperchloraemia ( 130 mmol / l ) , but ( from the parent study ) only mild anaemia ( 11 g / dl ) . most surprising in this context was a massive baseline plasma acetate ( 2.4 meq / l ) , which is 40 times the level reported from a previous study in dogs ( 0.06 mmol / l ) . the postshock acetate peaked at 5.8 meq / l , over 30 times that in the previous report ( 0.19 mmol / l ) . to our knowledge such prodigious acetate levels are unprecedented outside the setting of exogenous administration . in the parent study , ringer 's solution 15 ml / kg per hour was documented as infused during all but the shock phase . if this was ringer 's acetate , and if the animals had received both saline ( as stated by bruegger and colleagues ) and ringer 's acetate , then this would explain much . of relevance is a report that exogenous acetate can elevate hepatic citrate . although the authors acknowledge that they re - infused blood containing citrate phosphate dextrose solution during the shock phase , thus introducing exogenous citrate a final caveat is that charge and dissociation indices for human albumin used in this study differ from those for canine albumin , although the effect on sig calculations is probably small . until now , talk of unmeasured ions in critical illness has largely been speculative , based on discrepancies in ag or sig . nonetheless , since the late 1960s reports have emerged of accumulating tca cycle intermediates in shock and dysoxic states . the pattern reported by forni and colleagues in human metabolic acidosis differed substantially from the findings reported by bruegger and coworkers , with relatively small increases in isocitrate , -ketoglutarate , malate and d - lactate , and in some cases citrate and succinate . only on aggregate were these sufficient to inflate the ag . it is insufficient to invoke ' tissue stress ' to explain such increases in tca anions . elevations must be considered within the context of anaplerosis and cataplerosis , which combine to maintain adequate concentrations of tca intermediates . ag = anion gap ; sig = strong ion gap ; tca = tricyclic acid .

evidence is emerging that elevated concentrations of the intermediates of the citric acid cycle may contribute to unmeasured anions in critical illness . both the anion gap and the strong ion gap are used as scanning tools for recognition of these anions . the mechanisms underlying these elevations and their significance require further clarification .

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reliable information on morbidity and mortality is the key for evidence - based public health practice . more emphasis on estimating burden of diseases was given at global level , especially since the launch of global burden of disease study . while the decision - making priorities of global health authorities are dependent on these projected data , developing countries often lack the local data for proper public health planning . health professionals still fights to establish vital registration , while the morbidity surveillance is still in its initial stage . in countries where information is available , data from ambulatory care services , primary healthcare centers , and outpatient departments ( opd ) are often lacking . economic impacts of the mild to moderate ill health conditions are considerable given the large number of patients utilizing these services . as an example , in sri lanka , more than 43 million visits are made to the opds in government hospitals annually . given that the only 50% of outpatient care is delivered through public sector , the total outpatient visits are estimated to be more than 80 million , four times the sri lanka population of 20 million . despite this heavy burden , information on opd morbidities are not routinely collected and used in healthcare planning . as a preliminary study to assess the burden of disease and morbidity pattern in opd , we conducted a rapid survey in a tertiary care hospital in sri lanka . study sample consisted of opd patients visiting teaching hospital peradeniya , which is the teaching hospital for second largest medical school in sri lanka . three of the six authors physical presented at the opd during the study period , explained the procedure to patients , and consented patients filled a self - administered short questionnaire . a half - page questionnaire was used and the main problem which patients sort medical advice was inquired . a total of 3817 patients attended opd during the study period and 1908 were recruited as the study sample using the systematic sampling strategy . of them , 1439 completed the questionnaire with a response rate of 75.4% . a significantly higher number of females ( 924,64.2% ) visited the opd compared to males ( 515,35.8% ) ( chi square for goodness of fit 116 , p<0.001 ) . the age of the patients attending the opd ranged from 1 year to 89 years . the mean age of the study sample was 40 years ( sd = 19 years ) . majority of the females attending the opd were of middle age while males were distributed evenly among all age categories . the mean age of females was significantly higher than that of males ( t = 4.03 , p<0.001 ) . housewives constituted the major occupational group among females , accounting for 52% of the total sample , followed by adolescents ( 15.9% ) . ten leading cause of opd visits were nonspecific body aches and pains 225 ( 15.6% ) ; respiratory symptoms ( cough and cold ) 151 ( 10.5% ) ; abdominal pain 122 ( 8.5% ) ; fever - 117 ( 8.1 ) ; backache and joint pains 112 ( 7.8 ) ; skin conditions - 106 ( 7.4 ) ; constipation - 84 ( 5.8 ) ; chest pain 66 ( 4.6 ) ; diarrhea - 59 ( 4.1 ) ; and dog bite / s 51 ( 3.5 ) . table 1 shows the leading morbidities according to sociodemographic profile of the patients . among children ( 10 years)/school children , cough and cold was the commonest complaint followed by dog bites . constipation ( 14.5% ) was the commonest presenting complaint among tamils ( 6.3% ) but was not in the leading five commonest complaints among the other ethnic groups . main presenting symptom among adolescents was various skin conditions , which was third commonest condition among young adults . commonest presenting complaint by demographic characteristics among patients attending outpatient department of teaching hospital peradeniya , sri lanka ( n = 1 439 ) this could be explained partly from the so - called male - female health survival paradox ( i.e. , males report better health than females , but encounter higher mortality at all ages ) . there is growing evidence to conclude that men are healthier , but have substantially higher mortality rates . however , this could be also due to a gender difference in health - seeking behavior as shown in previous studies.[46 ] children less than 10 years accounted for only 5% of the opd patients , which shows a marked difference from the private sector utilization in sri lanka where 32% of encounters were reported as children , which was completely different from the findings of the present study . previously , respiratory tract problems were reported as the commonest encounter in government phc setting as well as in gp practice in sri lanka , with higher percentages ranging from 20% to 55%.[79 ] in our study , respiratory problems was the commonest among younger age groups . however , nonspecific body aches and pains was the leading encounter . however , this problem needs to be studied to provide meaningful services . despite having low annual numbers of rabies , dog bite showed to be a leading problem among children . reported constipation encounters as leading reason for opd care seeking among tamil ethnic group these observations from a single hospital could not be generalized to sri lanka or other developing countries . however , our study provides early evidence for probability of changing morbidity patterns with demographic transitions that should be taken into account in public health program planning .

background : global disease burden estimates often lack real data on morbidities , especially from patients treated in outpatient department ( opd ) . in sri lanka , around 40 million visits are made annually to the opds in government hospitals and we conducted a preliminary study to assess the morbidity profile of these opd patients.methods:patients attending the opd , in teaching hospital peradeniya , sri lanka , was recruited into the study using systematic random sampling procedure . a self - administered , structured questionnaire was used to collect data . investigators explained the study to patients and data collection was completed before seeing the physician . self - reported presenting complain was used to analyze the morbidity profile of the patients.results:the study sample consisted of 1 439 patients ( male - 515 , female - 924 ) . the mean age of the study sample was 40 years ( sd = 19 years ) . the mean age of the females were statistically significantly higher than that of the males ( t = 4.03 , p<0.001 ) . housewives constituted the major occupational group ( 52% ) followed by students ( 15.9% ) . the most common presenting complains reported were body aches and pains ( 15.6% ) , cough and cold ( 10.5% ) , and abdominal pain ( 8.5% ) . leading cause of hospital visit among different demographic categories showed statistically significant variations.conclusions:the morbidity pattern observed in this patient population was not previously reported . opd surveillance should be established to understand the changing pattern of minor ailments which might have a huge impact on health of the public .

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tinea corporis ( b35.6 ) caused by microsporum canis which is fungal species that causes numerous forms of disease . though mostly well known for ringworm in pets , it is also known to infect humans . we will report about a case , 22-year - old female , residing in a village , with typical changes of a mycotic infection caused by m. canis . dermatological description can be summarized with polymorphic erythematous , papulosquamous changes , erosions mainly on genital organ and spread to the thighs and lower abdomen which are accompanied with itching and burning . diagnosis b35.6 was determined on the basis of clinical appearance complemented with anamnesis , microscopic examination and culture . dermatophytosis ( tinea ) infections are fungal infections caused by dermatophytes - a group of fungi that invade and grow in dead keratin ( 1 ) . infection is limited to the dead layers of skin but encouraged by a damp and warm local environment . the infection can be transmitted to humans by anthropophilic ( between people ) , geophilic ( from soil ) and zoophilic ( from animals ) spread ( 2 ) . tinea cruris is three times more common in men than in women because of the scrotal anatomy ( 3 , 4 ) . itching , rash and nail discoloration are the most common symptoms of tinea infection ( 2 ) . tinea cruris , commonly referred to as jock itch , involves the medial aspect of the upper thighs ( groin ) ( 5 , 6 ) . complications such as secondary infection ( cellulitis and impetigo ) can lead to symptoms ( 2 ) . more unusually the lesions can appear as overlapping concentric circles ( tinea imbricate ) ( 7 ) . reactions to a dermatophyte infection may range from mild to severe as a consequence of the host s reactions to the metabolic products of the fungus , the virulence of the infecting strain or species , the anatomic location of the infection , and local environmental factors ( 8) . fungal transmission occurs through direct contact with infected persons , animals , soil or fomites . zoophilic sources should be identified ( if possible ) and treated to prevent human reinfection ( 9 ) . the classic presentation of tinea infection , known as ringworm , is a lesion with central clearing surrounded by an advancing , red , scaly , elevated border . inflammation assists in colonization and may result in vesicles on the border of the affected area . the presentations of tinea infections range from mild scaling and erythema to severe inflammation with bacterial superinfection . the differential diagnosis : multiform erythema , annular granuloma , nummular dermatitis , rosea pityriasis , versicolor pityriasis , psoriasis , secondary syphilis , candidal intertrigo . we report on a case diagnosed not directly due to delay of visiting a doctor by the patient because of stigma and prejudice attributed to local environment , lack of experience of the family doctor and specialist regional dermatologist in right diagnosis and treatment . the case is a 22-year - old female , with mycotic infection in the genital area ( figure 1 ) . female , 22 years old , lives in the village , hospitalized due to skin changes in the genital pubic part , thighs and lower abdomen , which are accompanied with extraordinary itching and burning . the changes had started much time before but she delayed her visit to the doctor to the point when her condition deteriorated with fever and temperature . the changes began with rash and itching presented in genitalia and then changes spread to areas around . in anamnesis , the patient denies that other members of the family have similar changes whereas she claims to own and have in family care a dog and a cat and no other domestic animals . she comes from a low level of socio - economic status . in dermatological description , changes are polymorphic , plaques in the pubic area with erythematous fluorescence , pustules , erosions , crusts and papulosquamous changes in the shape of circles in thighs and lower abdomen which are accompanied with intensive itching . the center of the circles is inactive while the surrounding is active with distinctive bordering line to the skin around . due to scratching because of itching diagnosis was determined on the basis of clinical appearance , anamnesis , positive dermatophytes microscopic view and culture m. canis . the patient was treated with general and local antimycotics ( terbinaphin 250 mg / day for 4 weeks ) , as well as with antibiotics according to sensitivity chart . from the anamnesis of the reported case is emphasized the continuous itching which never stopped for the whole time being described as terrible and which corresponds to the literature . also , the humidity of the genital area itself , washing with water after each defecation and urination ( islamic belief tradition ) , was a suitable ground for the development of the disease . the differential diagnosis was : multiform erythema , annular granuloma , nummular dermatitis , rosea pityriasis , versicolor pityriasis , psoriasis , secondary syphilis , candidal intertrigo but we were also based on clinical appearance , anamnesis complementing it with microscopic examination and fungal culture . we consider that the report on the mentioned case will be beneficial to family doctors so they can complement their professional experience with more extensive knowledge on clinical manifestation , diagnosis and differential diagnosis .

introduction : tinea corporis ( b35.6 ) caused by microsporum canis which is fungal species that causes numerous forms of disease . it is part of a group of fungi known as dermatophytes . though mostly well known for ringworm in pets , it is also known to infect humans . this fact makes this pathogen both anthrophilic and zoophilic in nature . microsporum canis is a communicable pathogen.case report : we will report about a case , 22-year - old female , residing in a village , with typical changes of a mycotic infection caused by m. canis . dermatological description can be summarized with polymorphic erythematous , papulosquamous changes , erosions mainly on genital organ and spread to the thighs and lower abdomen which are accompanied with itching and burning . diagnosis b35.6 was determined on the basis of clinical appearance complemented with anamnesis , microscopic examination and culture . the patient was treated successfully with general and local antimycotics and antibiotics .

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urinary tract infection ( uti ) is the most common infection contracted by renal allograft recipients . in patients of autosomal dominant polycystic kidney disease ( adpkd ) , cyst infection presents a complex diagnostic and therapeutic challenge , especially in the post transplant period . consequently , early and reliable detection of infected renal cyst is crucial for optimal patient management , especially when initial antibiotic therapy has failed . it has been infrequently reported in the post transplant scenario or in the adpkd patients . we report a case of post transplant xpn in the native adpkd kidney presenting as relapsing uti . 18-fluorodeoxyglucose ( fdg)-positron emission computerized tomography ( pet / ct ) scan allowed the exact localization of the infection in the renal parenchyma and guided the therapeutic procedure with subsequent resolution of uti . a 53-year - old male of adpkd - ckd on maintenance hemodialysis since one and half years received a deceased donor renal transplant at our institute . his postoperative recovery was uneventful and he was discharged on tenth post transplant day with a serum creatinine of 1.2 mg / dl . he presented two weeks later with complains of fever , malaise and dysuria . on clinical examination , he was hemo - dynamically stable but febrile . laboratory parameters included hemoglobin 10.2 gm / dl , leukocytes 8,600/cmm , platelets 2.9 lacs / cmm , glucose 186 mg / dl , urea 18 mg / dl , serum creatinine 1.7 mg / dl , sodium 138 meq / l , potassium 4.3 meq / l . urine analysis showed , albumin 1 + , 40 - 50 leukocytes /high power field ( hpf ) , red cells 4 - 5/hpf , no casts , bacteria , acid fast bacilli or fungus were found . chest x - ray was normal , abdominal ultrasonography showed multiple hepatic and renal cysts in native kidneys , but was not suggestive of any infection , graft kidney was unremarkable . he was treated with antibiotics and responded well to the same and later discharged . over the next three months patient presented twice with symptoms of uti and the urine cultures on both occasions grew escherichia coli . he was evaluated with ultrasonography and unenhanced computerized tomography ( ct ) , which revealed a normal transplant kidney and multiple cysts without evidence of any infection , hemorrhage or calculi in native kidneys . subsequently , patient underwent cystoureteroscopy with bilateral selective urine sampling from native kidneys , however culture revealed no growth . in an attempt to localize the source of infection it showed hyper - metabolic lesion arising in postero - inferior part of right native kidney [ figure 1 ] . pet / ct guided aspiration reveled purulent fluid , culture of the same yielded heavy growth of e. coli . on the basis of these findings , patient was subjected to right native kidney nephrectomy . the cut section of the gross specimen showed xanthomatous area [ figure 2 ] and the histopathology was suggestive of xpn [ figure 3 ] . patient made a good recovery with s. creatinine returning to 1.3 mg / dl and urine culture being sterile on subsequent follow - up of three months . pet / ct scan showing strong fdg uptake into postero inferior part of right native kidney ( arrow ) gross section of right kidney showing xanthogranulomatous area ( arrow ) light micrograph showing an interstitial infiltrate composed of neutrophils , mononuclear cells , and , most characteristically , lipid - laden macrophages ( arrow ) . febrile illness owing to complicated uti 's secondary to renal or hepatic cyst infection is a common cause of graft dysfunction . if not localized early and redressed they can be a source of significant morbidity especially in an immuno - compromised host . it is characterized by replacement of renal parenchyma with diffuse or segmental cellular infiltrate of lipid laden macrophages called foam cells . here , we report a case of rare occurrence of xpn in native polycystic kidney of a renal allograft recipient . in the literature , xpn in adpkd either in transplant scenario or otherwise has been infrequently reported.[46 ] in our case , conventional ct scan was non - contributory , however fdg pet / ct scan was helpful in localizing the site of infection . as the patient was not responding to conservative management it was decided to proceed with nephrectomy of infected kidney . xpn was subsequently established on evaluation of gross specimen [ figure 2 ] and histopathology [ figure 3 ] . fdg pet / ct scan in the recent times has emerged as a valuable tool for the transplant physician in localizing of infections especially in adpkd patients . pet / ct can overcome interpretive challenges in identifying tissue infection , based on the high metabolic activity and increased uptake of the glucose - analogue fdg by inflammatory cells . post transplant , uti especially in the adpkd patients is challenging to the transplant physician . this case highlights the rare occurrence of xpn as a cause of post transplant uti , especially in the absence of obstruction or stone disease . fdg pet / ct imaging is a valuable tool in both localization and subsequent planning of therapeutic interventions for complicated utis associated with adpkd transplant patients .

urinary tract infection ( uti ) is the most common infection contracted by renal allograft recipients . in patients of autosomal dominant polycystic kidney disease ( adpkd ) , cyst infection presents a complex diagnostic and therapeutic challenge especially in the post transplant period . accurate diagnosis forms the cornerstone in salvaging the graft from potentially catastrophic outcome . we describe a case of xanthogranulomatous pyelonephritis ( xpn ) in the native kidney in a patient of post transplant adpkd which presented as frequently relapsing uti with graft dysfunction where in accurate diagnosis was made possible with the aid of 18-fluorodeoxyglucose ( fdg ) - positron emission computerized tomography ( pet / ct ) .

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caesarean section is the delivery of the fetus , placenta , and membranes after the age of viability through an abdominal and uterine incision.1 there is a wide global variation in the incidence of caesarean section . the general range is from 5% to 25% with a continued rise in developed countries while in developing countries the rate is relatively low.12 in nigeria , the rate of caesarean section varies from one center to the other with 10.3% in enugu,3 10.5% ( makurdi),4 11.4% ( zaria),5 15.8% ( jos),6 and 20.3% in birnin - kebbi7 having been reported . the increase in caesarean section rates is largely driven by several factors which include societal demands for improved fetal outcome , protection of pelvic floor , and the aspiration of obstetricians to meet these demand.8 caesarean section can be performed either as an elective or emergency procedure . the former constitutes bulk of the cases.36 the indications for elective caesarean section are many and varying and are often relative rather than absolute . they include contracted pelvis , major degree placenta previa , two or more previous caesarean section , malpresentation , hiv infection in pregnancy , previous vesico - vaginal fistula repair , intrauterine growth restriction , and bad obstetric history.1469 usmanu danfodiyo university teaching hospital ( uduth ) sokoto , a 500 bed tertiary health center , serves sokoto , kebbi , and zamfara states in nigeria and also receives patients from the neighboring niger republic . the population served is mainly the hausa / fulani ethnic group and of islamic faith . girls are often married before the age of menarche thus making adolescent pregnancies and their associated complications common finding in the area.8 some of the complications of adolescent childbirth ( cephalopelvic disproportion with associated caesarean delivery and vesico vaginal fistula ) often necessitate elective caesarean section in subsequent pregnancies.1011 paucity of data in the literature on elective caesarean section in sokoto , north western nigeria informed this study . this was a retrospective analysis of 2284 consecutive caesarean sections performed at uduth sokoto over 9 years ( january 2002 to december 2010 ) . the records from the labor room and operating theater were retrieved and checked for caesarean deliveries . the delivery records of patients that had elective caesarean sections were obtained and relevant variables extracted . the variables include age , type of caesarean section , its indication , type of anesthesia used , and the maternal outcome . there were 22,985 total deliveries at the facility out of which 2284 were caesarean sections giving a caesarean section rate of 9.9% . a total of 1784 patients ( 79.3% ) had emergency caesarean section while 498 patients ( 21.8% ) had an elective procedure . general and spinal anesthesia were used in 253 ( 53.6% ) and 219 ( 46.4% ) of cases respectively . the age of the patients ranged from 18 years to 44 years with a mean of 31.23.6 years . table 1 shows the annual distribution of total , emergency , and elective caesarean section . it demonstrates a gradual rise in the rate of elective caesarean section increasing from 1.7% in 2002 to 3.2% in 2007 . repeat caesarean section for two or more previous caesarean section ( 31.1% ) and malpresentation ( 18.4% ) were the most common indication for elective caesarean operation . there were 18 maternal deaths from caesarean section and one from the elective caesarean procedure while the rest from emergency caesarean section . the cause of that single death from the former was anaphylactic reaction to general anesthetic agent . annual distribution of total , emergency , and elective caesarean section indications for elective caesarean section the caesarean section rate of 9.9% in this study is within the range of 6.4 - 32.1% reported in nigeria by previous authors.371214 however , the proportion elective caesarean section ( 20.7% ) relative to its emergency counterpart in the present study is much higher than 5.8 - 16.4% reported in most centers in the country.467 this may be attributed to relatively high rate of cephalo - pelvic disproportion arising from early marriage and teenage pregnancy in the study area10 which would have necessitated two previous emergency caesarean deliveries followed by the elective caesarean procedure . in addition , high rate of vesico - vaginal fistula from prolonged obstructed labor in the study zone15 may be contributory . this is because when the fistula is successfully repaired , subsequent deliveries are usually by elective caesarean operation.16 the rising trend of elective caesarean in these data has similarly been observed by previous authors.46 the reason for this may be the ever increasing list of the indications of elective caesarean delivery , larger cohort of patients with two or more previous caesarean section , and improved patient selection by clinicians with the use of better diagnostic techniques such as ultrasound machine.5 the most common indication in this study , repeat caesarean section , has also been reported in previous studies.4613 however , the second leading indication for the procedure in these data , malpresentation , is in contrast to bad obstetric history and hiv infection in pregnancy reported in jos and makurdi respectivelty.46 in conclusion , the rising trend of elective caesarean section observed in this study , underscores the need to better and improved patient selection together with counseling on its benefits and risks as elective caesarean operation though safer than its emergency counterpart is not entirely free of morbidity or mortality to both the mother and the baby . in addition routine use of spinal anesthesia in performing the procedure should be encouraged .

background : elective caesarean sections have been considered safer for both mother and the fetus compared to their emergency counterpart . however , emergency caesarean sections have continued to form bulk of caesarean deliveries in our facility.objective:the objective of this study was to determine the caesarean section rate together with the trend , indications , and maternal mortality associated with elective caesarean operation.materials and methods : a retrospective analysis of clinical records of all the patients that had caesarean section between january 2002 and december 2010 ( 9 years ) at usmanu danfodiyo university teaching hospital ( uduth ) sokoto , nigeria was conducted.results:during the 9 year study period , 2284 caesarean sections were performed out of 22,985 total deliveries at uduth sokoto , thus giving a caesarean section rate of 9.9% . emergency and elective operations accounted for 1784 ( 78.2% ) and 498 ( 21.8% ) of the cases respectively . the rate of elective caesarean section increased from 1.7% in 2002 to 3.2% in 2007 . thereafter it declined gradually to 1.8% in 2010 . repeat caesarean section ( 30.7% ) and malpresentation ( 17.1% ) were the most common indications for elective caesarean operation . there were 18 maternal deaths from caesarean section and only one from the elective caesarean procedure.conclusion:the rising trend in the elective caesarean section rate in this study underscores the need for better and improved patient selection together with counseling on its benefits and risks . this is because despite the fact that it is safer than emergency caesarean operation , it is not entirely devoid of complications . routine use of spinal anesthesia in performing the procedure should be encouraged .

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sequencing the complete genome of mycobacterium tuberculosis h37rv is a major milestone in the genome project and it sheds new light in our fight with tuberculosis . the genome contains around 4000 genes ( protein - coding sequences ) in the original genome annotation . however , we have found that the intergenic regions can exhibit expression signals , as evidenced by microarray hybridization . we conducted a genome - wide analysis using the affymetrix genechip to explore genes contained in the intergenic sequences of the m. tuberculosis h37rv genome . a working criterion for potential protein - coding genes was based on bioinformatics , consisting of the gene structure , protein coding potential , and presence of ortholog evidence . the bioinformatics criteria in conjunction with transcriptional evidence revealed potential genes with a specific function , such as a dna - binding protein in the copg family and a nickle binding gtpase , as well as hypothetical proteins that had not been reported in the h37rv genome . this study further demonstrated that microarray - based transcriptional evidence would facilitate genome - wide gene finding , and is also the first report concerning intergenic expression in m. tuberculosis genome .

sequencing the complete genome of mycobacterium tuberculosis h37rv is a major milestone in the genome project and it sheds new light in our fight with tuberculosis . the genome contains around 4000 genes ( protein - coding sequences ) in the original genome annotation . a subsequent reannotation of the genome has added 80 more genes . however , we have found that the intergenic regions can exhibit expression signals , as evidenced by microarray hybridization . it is then reasonable to suspect that there are unidentified genes in these regions . we conducted a genome - wide analysis using the affymetrix genechip to explore genes contained in the intergenic sequences of the m. tuberculosis h37rv genome . a working criterion for potential protein - coding genes was based on bioinformatics , consisting of the gene structure , protein coding potential , and presence of ortholog evidence . the bioinformatics criteria in conjunction with transcriptional evidence revealed potential genes with a specific function , such as a dna - binding protein in the copg family and a nickle binding gtpase , as well as hypothetical proteins that had not been reported in the h37rv genome . this study further demonstrated that microarray - based transcriptional evidence would facilitate genome - wide gene finding , and is also the first report concerning intergenic expression in m. tuberculosis genome .

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laparoscopic supracervical hysterectomy ( lsh ) has continued to represent a favorable alternative to total abdominal hysterectomy ( tah ) for the treatment of benign gynecologic conditions , particularly due to the reduced complication rates , shorter surgery / hospital stay , and prompt resumption of patient daily living activities . nevertheless , studies continue to suggest that lsh should not be used as a treatment for benign gynecological conditions , particularly cervical dysplasia . the purpose of this commentary is to address the primary objections against lsh and further illustrate the benefits inherent in this procedure . initially , the primary impetus for removal of the cervix at the time of hysterectomy in patients with benign conditions was to prevent cervical cancer . however , the incidence of cancer in the cervical stump is extremely low and primarily preventable due to latent disease progression , pap smear technology , and hpv screening . therefore , removing this organ solely for the purpose of preventing cervical cancer appears counterintuitive , especially considering that both at - risk patients and the general nonhysterectomized population receive the same recommended screening guidelines . since lsh involves the removal of the uterine section ostensibly related to the specific condition , the operation fixes many gynecologic problems while it conserves the patient 's anatomy and sexual function by retaining the cervix and its mucous - secreting glands . furthermore , the cervix is not typically associated with pelvic pain or bleeding , and thus patients can thereby avoid the common complaints of vaginal dryness and dyspareunia . studies have further indicated that removal of the normal cervix can cause untoward bladder and bowel consequences , including prolapse and urinary incontinence . additionally , prior research has reported that lsh outcomes coincide with favorable rates of prolapse and vaginal cuff dehiscence ( vcd ) . in particular , hur et al examined the prevalence of vcd in a large hysterectomy study , indicating that the condition has a significantly following tah compared with lsh . randomized controlled trials and metaanalyses have documented that lsh is associated with a higher incidence of cervical stump complications ( eg , cyclical bleeding and urinary incontinence ) . however , the cyclical bleeding with lsh is often slight and can be tolerated if the patient receives adequate preoperative counseling . in terms of stress urinary incontinence , tah appears to be associated with more favorable outcomes compared with lsh , whereas there were no reported lower urinary tract symptom ( luts ) differences between the 2 procedures . we contend that because vaginal suspension alters the bladder neck angle and reduces postoperative incontinence , when performing lsh , consideration for suspending both the vagina and the cervical stump may significantly mitigate stress urinary incontinence . while there were no reported differences between tah and lsh regarding the incidence of luts , urinary tract infections , incomplete bladder emptying and voiding complications increased after tah at 1-year follow - up but decreased in the lsh patients . in an earlier surgical study , gimbel et al also reported a much higher incidence of serious adverse events and perioperative blood loss in patients treated with tah compared with those treated with lsh . furthermore , the tah group exhibited more bladder / ureteral injuries , underwent longer operative times . patients who present with recurrent cervical dysplasia should consider having their cervix removed if a total hysterectomy is warranted . however , when a patient initially presents with cervical dysplasia , lsh may be preferable to hysterectomy particularly given the reportedly lower complication rates , reduced surgical time , and earlier recovery . the combination of improved prevention programs , patient adherence to annual screening recommendations , and an informed community appreciation of the virus 's vaccination distribution may further render this issue inconsequential . we suspect that the controversy surrounding the removal of the cervix is partially attributed to both insufficient lsh outcome studies and because many gynecologic surgeons are not formerly trained or experienced with this treatment option . while we recognize that both the american college of obstetrics and gynecology and a recent cochrane analysis clearly state that tah is more beneficial than lsh in treating benign gynecologic conditions , clinicians should strongly consider the several encouraging lsh findings and emerging studies that continue to substantiate the efficacy of lsh for treating many common benign gynecologic conditions .

recent results from metaanalyses and observational studies have suggested that total abdominal hysterectomy ( tah ) is superior to laparoscopic supracervical hysterectomy ( lsh ) for the treatment of benign gynecologic conditions . however , because lsh is associated with fewer intraoperative complications , shorter operative time , and preserves patient anatomy and sexual function in comparison with tah , clinicians should reconsider the benefits of lsh .

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spastic torticollis , also known as stiff neck or wryneck , is a condition in which the head is laterally flexed and rotated on the neck , secondary to painful spasm of the neck muscles . there may be a report of the patient having slept in a draft from a fan , open window , or air conditioner . the patient is generally afebrile , and if there is any history of trauma , it is of the mildest variety . chloroethane ( ethyl chloride ) spray is a vapocoolant applied topically in the treatment of athletic injuries . the manufacturer indicates that it may be used as a counterirritant in the management of myofascial pain and muscle spasm . we reviewed the literature and could find no large study on pediatric patients regarding this usage . we report our experience with the use of chloroethane spray treating torticollis in 66 patients ranging in age from 1 to 16 years . patients presenting to the pediatric emergency service of a 600-bed inner - city hospital with the compliant of stiff neck were selected for treatment . an initial evaluation was performed , which included a medical and family history , a physical examination , and x - ray study of the cervical spine ( a - p , lateral , and open mouth views ) . the patients were enrolled into either group 1 , usage of ethyl chloride spray , or group 2 , usage of normal spray . in the patients enrolled in group 1 ( after explaining the procedure to the parent and child and obtaining informed consent ) , the chloroethane spray bottle was held inverted 12 inches directly over the point of maximal neck tenderness . the valve of the bottle was opened , allowing the liquid to leave as a fine jet stream . the stream was left in contact with the skin for 4 to 5 seconds or until frosting of the skin occurred . the procedure was considered successful if , after a 5-minute waiting period , the patient was able to freely and painlessly move his or her head and neck in the opposite side . for the control group , normal saline is applied as a spray using a syringe with plastic catheter over the point of maximum tenderness and asked to move the neck after 5 minutes and note if patient can move the head and neck freely in the opposite side . a total of 132 children with a mean age of 8.97 years ( range = 1 - 16 years ) presented to the emergency room with torticollis over a period of 3 years and were enrolled in the study . of the 132 , patients in group 1 were treated with chloroethane spray and those in group 2 were treated with normal saline spray . of the 66 patients treated with chloromethane spray , 63 ( 95% ) responded to the treatment as evidenced by their subsequent ability to move the head and neck freely ( see table 1 ) . no patients returned for additional treatment . of the patients in group 2 , who treated with normal saline spray , no patient responded to saline spray with ability to move the head freely in the opposite side ( see figure 1 ) . series 1 : patients rxed with chloroethane spray ( 63/66 positive response and 3/66 negative response ) . the torticollis was in several cases associated with a local head or neck condition , but 46.97% of the cases involved no underlying pathology ( table 2 ) . of the 3 treatment failures , 2 occurred in patients with neck trauma and 1 failure occurred in a patient with cystic hygroma . conditions associated with spastic torticollis . abbreviation : uri , upper respiratory infection . to test the null hypothesis that the percentages improved in the 2 groups equally , we calculated the z statistic . the z statistic of 24 corresponded to a p value < .0001 , whether the test is 1-sided or 2-sided . to test the null hypothesis that the percentages improved in the 2 groups equally , we calculated the z statistic . the z statistic of 24 corresponded to a p value < .0001 , whether the test is 1-sided or 2-sided . torticollis is a condition in which the head is laterally flexed and rotated on the neck due to shortening or spasm of the sternocleidomastoid muscle . acquired torticollis can be caused by a variety of problems including cold exposure , minor neck muscle trauma , and any inflammatory condition of the neck such as cervical lymphadenitis , or retropharyngeal abscess . less common causes include drug ingestion ( eg , phenothiazines ) and a variety of neurological conditions such as dystonia musculorum deformans , brain stem , or posterior fossa tumor or cyst . we focus on describing chloroethane treatment for spastic torticollis caused by sternomastiod spasm that may be primary or secondary to a local inflammatory condition . this form of torticollis is most often treated with warm compresses , analgesics , and muscle relaxants . it is thought that the relief is the result of the wrong acting as a counterirritant or a local anesthetic or by a placebo effect . similarly , a vapocoolant therapy has been described to successfully relieve acute myofascial trigger with point pain in children . in conclusion , from our study , for children and adolescents with spastic torticollis , chloroethane spray was more superior to normal saline in the pediatric emergency room .

objective . a study to determine the efficacy of chloroethane spray compared to normal saline in the treatment of spastic torticollis in children and adolescents . hypothesis . chloroethane spray is more superior to normal saline for the treatment of spastic torticollis in children and adolescents in the pediatric emergency room . design . prospective randomized study . setting . urban inner - city hospital pediatric emergency department . methods and results . all children and adolescents ( between the ages of 1 and 16 years ) presenting to the author with the complaint of stiff neck were enrolled in the study . a total of 132 patients were enrolled . after complete evaluation to rule out cervical spine injury , a central neurological cause , patients were enrolled in the study . sixty - six patients were treated with chloroethane spray to the neck and the other 66 were given normal saline as placebo . sixty - three out of 66 patients treated with chloroethane spray achieved relief in 5 minutes as demonstrated by painless and free movement of the head and neck . no adverse effects were observed . the patients treated with placebo have no relief in 5 minutes . to test the null hypothesis that the percentages improved in the 2 groups equally , we calculated the z statistic . the z statistic of 24 corresponded to a p value of < .0001 , whether the test is 1-sided or 2-sided . chloroethane spray treatment was superior to placebo with a high statistical significance . conclusion . for children and adolescents with spastic torticollis chloroethane spray was more superior to normal saline in the pediatric emergency room .

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malignant melanoma is a malignant tumor of the melanocytes or the cells that develop from melanocytes . histologically , malignant melanomas are asymmetrical and poorly circumscribed lesions with architectural disturbance and usually marked cytological atypia . the major histologic subtypes of melanoma are superficial spreading melanoma , nodular melanoma , lentigo maligna melanoma and acral lentiginous melanoma , which show a variety of cytomorphological features , architectural patterns and stromal changes that may be observed in malignant melanomas . moreover , there are numerous uncommon histological variants , including clear , signet ring , pseudolipoblastic , rhabdoid , plasmacytoid and balloon cell melanomas . among them , balloon cell malignant melanoma ( bcmm ) is the rarest variant composed of large , polygonal , foamy cells with abundant cytoplasm . these features can also be seen in balloon cell nevus ( bcn ) , but the presence of nuclear pleomorphism , atypia , mitoses and a lack of maturation of melanocytes with descent into the dermis help to differentiate bcmm . a balloon cell change may occasionally be observed in conventional melanomas , but it mostly remains in focal areas . malignant melanoma accounts for only 35% of primary cutaneous malignancies and it mostly develops in people over 50 years . this report presents a young patient of primary bcmm with near - complete effacement by foamy cells . a 32-year - old female presented to our hospital with a tumor on the left lumbar region . the lesion of concern was an erythematous and focal eccentric pigmented nodule of 15 mm in diameter ( fig . the clinical appearance of the lesion raised a suspicion of malignancy , and surgical resection was performed . the surgically resected specimen showed a nodule with focally pigmented areas , and the cut surface of the nodule was asymmetrical and not ulcerated . histological examinations showed a skin fragment with nearly complete effacement by foamy cells and asymmetry ( fig . the foamy cells in the superficial dermis extended to the fatty tissue to a depth of 10 mm . 1c ) . the intraepidermal component was composed of both nested and single atypical melanocytes with areas of intraepidermal pagetoid spread ( fig . the pathological diagnosis was of bcmm ( breslow depth 10 mm , clark level v ) without ulcer . a month after the excision , the excised bilateral inguinal lymph nodes showed diffuse replacement of the lymph nodes by foamy cells ( fig . bcmm is an uncommon histopathological subtype of malignant melanoma that was first described by gardner and vazquez in 1970 . , balloon cell changes of melanocytes have been noted in numerous neoplasms , including melanoma . histologically differential diagnosis of bcmm includes bcn , clear cell sarcoma , clear cell metastatic renal cell carcinoma , basal cell carcinoma , squamous cell carcinoma and dermatofibroma . the clinical appearance could also be interpreted as that of spitz nevus , basal cell carcinoma , eccrine poroma or eccrine porocarcinoma . a microscopic examination showed a dominant nodular component comprised exclusively of markedly distended epithelioid melanocytes showing abundant vacuolated cytoplasm . bcmm differs from bcn in its nuclear pleomorphism , atypia and the lack of melanocyte maturation with a decent proliferation into the dermis . while fontana - masson staining of melanoma cells is generally positive , balloon cells in bcmm are generally negative in this stain [ 4 , 5 , 6 , 7 ] the balloon cell component of our current case was also stained negative with fontana - masson . the occurrence of the foamy cells has been suggested to be related to an enlarged defective melanosome formation . they are likely developed by the transformation of epithelioid cells , because balloon cells are mainly observed at metastatic or recurring lesions . previous case reports suggested that patients with bcmm may have longer survivals than those without balloon cell changes . however , the actual mortality rate of bcmm tends to be high because bcmm are thick at the time of presentation . in fact , there was no apparent difference in a more recently reported survival rate between bcmm and other variants of melanoma . malignant melanoma may affect people of all ages but is mostly observed in people over the age of 50 years . the case reported here is a young case of primary bcmm with near - complete effacement by foamy cells .

balloon cell malignant melanoma ( bcmm ) is a very rare malignant melanoma subtype . the clinical appearance of bcmm varies ; it may be nodular , ulcerated , polypoid , papillomatous and often non - pigmented . the tumor cells histologically appear large , polygonal or round and contain abundant granular or vacuolated cytoplasm . we herein report the case of a 32-year - old female who presented with a focal eccentric pigmented mass in the left lumbar region of 15 mm in diameter that had been present for several years . she underwent tumor excision . the histopathological analysis showed epithelioid melanocytes with clear cytoplasm . an immunohistochemical analysis revealed that the cells were positive for hmb-45 and s-100 protein and negative for cytokeratin . the balloon cell component stained negative for fontana - masson . a month later , the patient underwent excision of the bilateral inguinal lymph nodes and metastatic bcmm was revealed . the lymph node metastases showed the complete replacement of lymph nodes by balloon cells . a diagnosis of bcmm ( breslow depth 10 mm , clark level v ) without ulcer was rendered . staining with ki-67 was positive in almost 44% of the balloon cells .

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it accounts for < 1% of all hernias . typically , they manifest in multiparous , thin females within their seventh to ninth decades of life . patients frequently present with symptoms of intestinal obstruction and , occasionally , pain along the distribution of the obturator nerve on the ipsilateral side ( howship romberg sign ) . however , the diagnosis can be difficult to make and delay in diagnosis and surgical intervention contributes directly to high morbidity and mortality rates . the authors report the successful laparoscopic management of an acute presentation of an obstructed obturator hernia . an 85-year - old female with a background of trans - abdominal hysterectomy , hypertension and a previous thyroid lobectomy , presented acutely with a 1-day history of upper abdominal pain radiating down her left leg associated with numerous episodes of emesis . her bowels had opened three times in the previous 24 h. she was anorexic for the previous 24 h. she reported a similar episode requiring hospitalization 3 weeks before , which was treated non - operatively in another institution . on examination , she was treated presumptively as a small bowel obstruction and non - operative measures were employed and the patient proceeded to have a computed tomography ( ct ) scan of the abdomen and pelvis , which indicated proximal small bowel obstruction secondary to a left obturator hernia ( fig . 1 ) . she proceeded to emergent laparoscopy and subsequent mesh repair of left obturator hernia , containing an obstructed loop of small bowel . proximal small bowel obstruction secondary to a left obturator hernia within white outline . under general anaesthetic , the optical technique for access was utilized at the umbilicus with a 5 mm port . two further working ports , a 5 and 10 mm , were placed in the right lower quadrant and right hypochondrium , under direct vision . findings included visualization of small bowel dilatation down to small bowel in a left obturator hernia with an incidental left femoral hernia containing omentum ( fig . the incarcerated small bowel was reduced using a pair of non - traumatic forceps and deemed viable . figure 2:intraoperative image showing left sided obturator hernia within white outline and incidental femoral hernia at 11o clock position . intraoperative image showing left sided obturator hernia within white outline and incidental femoral hernia at 11o clock position . sommerville , nj , usa ) tacked with absorbatack ( covidien , mansfield , inc . , this then allowed the mesh to be spread laterally and fixed to the transversalis fascia . the femoral hernia was repaired with 2 2/0 vicryl ( ethicon , inc . , the patient did suffer a post - operative pneumonia but was treated appropriately , made a good recovery and was discharged home well . conditions associated with long - standing increased intra - abdominal pressure , weight loss that leads to a decreased peritoneal fat and multiparity are implicated on the basis of laxity of the parietal peritoneum . all are believed to increase the risk for development of an obturator hernia and women are affected nine times more frequently than men . the obturator membrane covers most of the foramen , except at the anterior superior aspect . the anatomic formation of obturator hernia has been previously described in detail in the literature , but the basic premise of the aetiology and pathogenesis is based on the loss of preperitoneal fat or lymphatic tissue that occupies the obturator canal . classic features of an obturator hernia : ( i ) a palpable mass in the groin with the patient supine , and the thigh flexed , adducted and rotated laterally ; ( ii ) intestinal obstruction ; ( iii ) previous attacks of bowel obstruction resolving spontaneously ; ( iv ) the howship romberg sign is medial thigh and hip pain exacerbated by adduction and medial rotation of the thigh and relieved by thigh flexion . the usefulness of ct in diagnosis was first reported by cubillo in 1983 and it has been assisting in the earlier diagnosis of obturator hernia but despite this post - operative mortality has not improved remarkably . however , several studies have shown the feasibility of laparoscopic techniques for the management of incarcerated obturator hernia . the transabdominal preperitoneal repair for obturator hernias is the preferred technique as it allows assessment of the visceral contents . the current trend is to repair the defect using prosthetic material ; however , there is no robust evidence in the literature to compare and contrast the superiority of mesh repair over other repairs in obturator hernia . in conclusion , we present this rare case to raise awareness of a rare presentation but with significant morbidity and mortality if a high index of suspicion is not maintained . this case illustrates the usefulness of ct in diagnosing obturator hernia and it also confirms that laparoscopic mesh repair of an incarcerated obturator hernia is safe and technically feasible .

obturator hernia is a rare pelvic hernia that occurs primarily in multiparous , elderly ( > 70 years of age ) , thin females . this case highlights the successful laparoscopic mesh repair of an incarcerated obturator hernia in an octogenarian.the authors report a case of an incarcerated obturator hernia in an elderly female with subsequent high - grade small bowel and its successful laparoscopic operative management . a review of the relevant literature was also performed following a search on the online literature databases such as pubmed and embase . laparoscopic mesh repair of the incarcerated obturator hernia and an ipsilateral femoral hernia found incidentally was successfully performed . a review of the literature showed a significant burden of morbidity and mortality associated with obturator hernias . laparoscopic mesh repair has been previously shown to be a safe therapeutic modality . small bowel obstruction and leg pain in a thin elderly lady should arouse suspicion for an incarcerated obturator hernia . laparoscopic management of an incarcerated obturator hernia is a feasible and safe therapeutic option .

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the us chinese anti - cancer association ( uscaca , , http://www.uscaca.org/ ) is a non - profit professional organization founded in 2009 . with members from academia , industry and government , uscaca facilitates collaboration among cancer research and physicians in the united states and china . our current focus is on expediting novel cancer drug development by fostering clinical trial networks , sharing best practices and knowledge of clinical trials , and providing education and training opportunities . uscaca collaborates with chinese anti - cancer association ( caca , ) , chinese society for clinical oncology ( csco ) , and other pro - fessional associations . the uscaca - csco joint session organizing committee co - chairs : jian ding , helen chen , li yan uscaca : roger luo , pascal qian

the us chinese anti - cancer association ( uscaca ) teamed up with chinese society of clinical oncology ( csco ) to host a joint session at the17th csco annual meeting on september 20th , 2014 in xiamen , china . with a focus on breakthrough cancer medicines , the session featured innovative approaches to evaluate breakthrough agents and established a platform to interactively share successful experiences from case studies of 6 novel agents from both the united states and china . the goal of the session is to inspire scientific and practical considerations for clinical trial design and strategy to expedite cancer drug development in china . a panel discussion further provided in - depth advice on advancing both early and full development of novel cancer medicines in china .

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the overall annual incidence of intussusception in adults in the general population has been reported to be as low as 2 cases/1 000 000 persons ; adults account for ~5% of confirmed intussusceptions . as high as 90% of cases of adult intussusception are due to a pathological process , with neoplasms accounting for ~60% of identifiable leadpoints . one 6-year prospective study encompassing screening of 380 999 computed tomography ( ct ) scan reports that were read as intussusception , 0.04% of cases were in adults . in adults , surgery is typically performed owing to the likelihood that a neoplastic or otherwise chronic pathology is the cause of the intussusception . indications to take any case to the operating room include large caliber of telescoped bowel , long length of telescoped portion , identifiable lead point and evidence of obstruction [ 24 ] . the former indications owe to the increased likelihood of malignancy requiring surgical exploration and incision , and bowel wall and mesenteric ischemia in the setting of large intussusceptions . a 61-year - old gentleman presented with a 3-day history of right - greater - than - left lower quadrant abdominal pain , distention , anorexia and one episode of emesis . the patient also reported only consuming liquids for 57 days prior to presentation as solid foods caused significant discomfort . three weeks prior , colonoscopic evaluation of his cramping was aborted at 20 cm due to an impassable sigmoid stricture . several hyperplastic polyps and one tubular adenoma his abdomen was distended and tympanic , with tenderness and fullness appreciated in the right lower quadrant . 1 ) demonstrated small bowel obstruction due to an ileocolic intussusception , from the ileocecal valve to the splenic flexure , and collapsed distal colon . figure 1:top left : origin ( arrow ) of invagination in the right lower quadrant . the telescoped bowel contained terminal ileum , cecum , appendix and the entire ascending colon ( fig . a 4.5 cm 5 cm mass was identified at the lead point , the ileocecal valve . resection included the right hemi - colon , cecum , appendix and 15 cm of terminal ileum . a diverting ileostomy was created as well as a mucus fistula for post - operative antegrade colonoscopic evaluation of the remaining colon . figure 2:left : stills from intraoperative video recording demonstrating the reduction of the intussusception in order to explore the lead point . right : ischemic terminal ileum ( arrow ) and palpation of the lead point at the ileocecal valve . left : stills from intraoperative video recording demonstrating the reduction of the intussusception in order to explore the lead point . right : ischemic terminal ileum ( arrow ) and palpation of the lead point at the ileocecal valve . additional tubulovillous adenomas , tubular adenomas and hyperplastic polyps were identified throughout the excised portion of bowel . figure 3:low - power ( left ) and high - power ( right ) views of lead point tumor demonstrates > 50% of the tumor composed of pools of mucin ( solid arrow ) , invasive tumor cells ( dotted arrow ) with hyperchromatic chromatin , crowded nuclei , surrounded by pools of mucin [ 57 ] . low - power ( left ) and high - power ( right ) views of lead point tumor demonstrates > 50% of the tumor composed of pools of mucin ( solid arrow ) , invasive tumor cells ( dotted arrow ) with hyperchromatic chromatin , crowded nuclei , surrounded by pools of mucin [ 57 ] . this patient 's presentation is exceptionally unique for both the size and cause of intussusception . to our knowledge , the few cases we found were always in the setting of malignancy , the patients presented with a similar chronologic progression with escalation of symptoms including liquid - only diets shortly before presentation . additionally , the very large intussusceptions were always found in the setting of malignancy [ 1012 ] . it seems that a favorable ( mobile ) anatomy with an indolent process is a common thread amongst these rare cases . further compounding the uniqueness of this case is the lead point tumor 's location and histology , along with the presence of additional terminal ileum and colonic polyps . the annual incidence in the united states of small bowel adenocarcinoma from 1973 - -2005 is 6.8 cases per 1,000,000 person years , as calculated by surveillance epidemiology and results ( seer ) program . additionally , ileocecal adenocarcinoma of any type is sparsely described outside of a few case reports [ 8 , 9 , 1315 ] . mucinous adenocarcinoma tends to be a locally aggressive tumor , and metastasizes by redistribution phenomenon rather than vascular or lymphatic invasion . presently , we have no unifying diagnosis to correlate the multiple lesions found throughout the telescoped bowel and distal 20 cm of colon and rectum . however , it is currently estimated that up to 40% of patients with extensive polyps and a positive family history are ruled out for hnpcc by genetic testing for mismatch repair and msi , as was the case for this patient . nevertheless , the unique presentation of this patient allowed for expeditious removal of a classically aggressive tumor , in what appears to be the first reported case of a long - tract intussusception secondary to a mucinous adenocarcinoma of the ileocecal valve .

abstractintussusception in adults lacks specific symptoms and is often diagnosed emergently when they present with obstruction . though intussusception certainly varies in size and location , the increased likelihood of ischemia or obstruction make large intussusceptions very rare in the literature . a patient admitted to our facility for small bowel obstruction was found to have extensive intussusception from the right lower quadrant to the splenic flexure , where a lead point was identified . histopathology revealed multiple satellite lesions surrounding the lead point tumor , which was found to be invasive mucinous adenocarcinoma of the ileocecal valve . while malignancy is found in 60% of lead point identifiable adult intussusceptions , a malignancy is always found in the case of an exceptionally large intussusception .

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the first important discussion regarding sialosis in dental reports was mentioned 35 years ago and since then little has been published . sailadenosis refers to noninflammatory , often recurrent enlargement of the salivary glands , most frequently , the parotids . it is usually associated with various underlying disorders that include diabetes , alcoholism , malnutrition , anorexia nervosa , bulimia , etc . , the management of sialadenosis depends upon identification of the underlying cause that must then be corrected . a 45-year - old female came with a swelling at the left preauricular region measuring 3 cm 3 cm . ultrasonography showed single , well - circumscribed swelling measuring 3 cm 3 cm in the left preauricular region which was suggestive of benign salivary gland lesion . fine needle aspiration cytology showed moderately cellular smears having acinar epithelial cells arranged in clusters , papillae , and glandular pattern as well as scattered singly [ figure 1a ] . individual cells were round , having round uniform nuclei and a moderate amount of cytoplasm [ figure 1b ] . in areas ( a ) photomicrograph showing moderately cellular smears having acinar epithelial cells arranged in clusters , papillae , glandular pattern , and scattered singly ( b ) individual cells were round , having round uniform nuclei , and a moderate amount of cytoplasm ( c ) in areas mild cellular enlargement , nucleomegaly , and hyperchromasia were noted . sialadenosis is a recurrent , noninflammatory , nonneoplastic enlargement of salivary glands usually associated with an underlying systemic disorder . pape et al . reported in his series of cases , four cases of unilateral sialadenosis . sialadenosis usually occurs in association with a variety of conditions including diabetes mellitus , alcoholism , endocrine disorders , pregnancy , drugs , bulimia , eating disorders , idiopathic , ect . clinically , it presents as soft , often bilateral , usually painless , and recurrent swelling of the parotid gland . fine needle aspiration yields cellular smears having acinar epithelial cells adherent to thin fibrovascular stroma . mainly large numbers of naked nuclei of epithelial cell origin were seen in the background . a similar condition that can mimic sialadenosis is low grade acinic cell tumor particularly on cytology . atypical nuclear features were more prominent in acinic cell tumors as compared to sialadenosis . in our case , the distinguishing cellular feature for acinic cell carcinoma includes large nuclei , grainy eosinophilic cytoplasm , and neoplastic cells are arranged singly or in small clusters . in addition , usually there is an absence of other normal salivary gland structures such as duct epithelium and interstitial adipose tissue . these are important features useful for differentiating acinic cell carcinoma from sialadenosis and normal salivary gland enlargement . the diagnosis of silaladenosis must exclude inflammatory causes of salivary gland swelling , particularly sjogren 's syndrome , human immunodeficiency virus ( hiv ) infection , sarcoidosis , and lymphoepithelial diseases by relevant investigations . other condition of sialadenitis will be excluded as it contains inflammatory cells on the background . the treatment of sialadenosis is unsatisfactory but it should be aimed at the correction of the underlying disorder . we are presenting this case for its rarity and its important differentiation on cytology smears from other parotid lesions . in the work - up of salivary gland swelling , it is important to recognize on cytological evaluation of these underestimated entities which do not necessarily require surgical treatment and can be treated with an underlying systemic cause .

a diffuse , chronic , usually bilateral , noninflammatory , nonneoplastic enlargement of major salivary glands is termed as sialosis or sialadenosis . it is an extremely uncommon cause for enlargement of the parotid gland . we hereby present a case of a 45-year - old female patient having a swelling at the left preauricular region . the swelling was gradually increasing in size since 6 months . on clinical examination , the swelling was 3 cm 3 cm , mobile , and nontender . on ultrasonography , it was suggestive of benign parotid lesion or parotitis with cervical lymphadenopathy . on fine needle aspiration cytology , it was suggestive of sialadenosis . this is an extremely rare salivary gland lesion with specific cellular features . it is very important to distinguish sialadenosis from other causes of enlargement of the parotid gland as treatment modality differs .

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the institutional review board approved this case report prior to any review of medical records . an 80-year - old man was transferred to our institute because of an incidentally detected renal tumor . the patient underwent a right partial nephrectomy due to a previously diagnosed rcc eight years prior . recent routine follow - up ct images , which covered the lung and abdomen , revealed a right renal mass , a right adrenal mass , and three pulmonary nodules ; all of which were not seen on prior ct images ( figs . 1a - c ) . the right renal tumor and adrenal tumor had maximum diameters measuring 2.0 cm and 1.8 cm , respectively . in addition , the pulmonary nodules , with maximum diameters ranging from 8 to 10 mm , were seen in the right upper lobe , left upper lobe , and left lower lobe . the treatment modality decided upon was an rf ablation for the cytoreductive removal of the right renal tumor . however , the histological results were not confirmed before the ablation as these lesions were clinically considered to be recurrent or as metastatic lesions from the previously removed rcc . an internally - cooled rf system ( radionics , burlington , ma ) was used for the ablation of the right renal tumor , along with an electrode ( cool - tip , valleylab , boulder , co ) that was kept below 20 by means of chilled water supplied by a peristaltic pump . we selected an rf electrode with a 2 cm active tip , which corresponded to the size of the right renal tumor . the electrode was appropriately targeted in the center of the renal tumor under ultrasound ( us ) guidance and performed two cycles of rf ablation . for the first ablation cycle , for the second rf cycle , reduced electrical power ( 80 w ) was delivered for 3 minutes due to severe pain . for pain relief , a total of 50 mg of penthidine hci ( hana pharmacy corporation , hwasung , korea ) was intravenously infused during the rf ablation . a post - ablation ct performed 10 months after the ablation showed a lack of tumor enhancement within the right renal tumor ( fig . the size of the recurrent renal tumor decreased to a maximum diameter of 1.4 cm . all of the metastatic pulmonary nodules became too small to be measured on ct images ( fig . in addition , the right adrenal tumor decreased in size to a maximum diameter of 1.4 cm ( fig . chemotherapy and immunotherapy was not performed due to the poor general condition and old age of the patient . spontaneous tumor regression has been reported to occur for some types of malignant tumors , although the incidence is rare . this phenomenon may be defined when the tumors partially decrease or totally disappear without any treatment . an rcc can be a spontaneously regressing tumor and is in fact known to develop in less than 1% of rcc cases ( 1 - 5 ) . spontaneous regression of metastatic lesions from an rcc have occurred frequently following a nephrectomy , radiotherapy , or embolization ( 1 - 4 , 6 ) . as with our case , metastatic pulmonary lesions were reported to spontaneously regress following an rf ablation of a tumor ( 7 ) . these cytoreductive treatments seemed to play a major role in the spontaneous regression ; however , the role of nephrectomy accounted for only less than 50% of all reported cases with spontaneous regression ( 4 ) . immunological responses to an rcc are also quite controversial , but the use of interferon to strengthen the hosts immunity , which may ultimately improve the survival of patients with advanced stage rcc should be performed ( 8) . in general , here has been a consensus that an rf ablation can be used in treating patients with a localized rcc , which is difficult to remove surgically . recently , this treatment modality has been considered as a good alternative treatment option because of its minimally invasive nature and excellent clinical outcome . for this reason , an rf ablation might be as beneficial as a nephrectomy at inducing the spontaneous regression of rcc , although their mechanisms are unknown . both the rf ablation and a nephrectomy may be involved in stimulating the host 's immune system as if these treatments naturally kill the cells of rcc as with the use of immnunotherapy using interferon . a literature search revealed that our case was found to be the second case report on the spontaneous regression of pulmonary metastases following an rf ablation of the recurrent rcc ( 7 ) . however , we could not find any cases with spontaneous regression of adrenal metastasis from the rcc following ablation . the rf ablation might be recommended as a good alternative treatment when a cytoreductive nephrectomy is required in patients with metastatic lesions , but are in poor general physical condition . in conclusion , spontaneous regression of metastatic lesions from an rcc is extremely rare , but can result following the rf ablation of the tumor .

the spontaneous regression of metastatic lesions from renal cell carcinoma ( rcc ) is extremely rare , but may be encountered following cytoreductive treatments . we report a case of a recurrent rcc with multiple metastatic lesions which spontaneously regressed after undergoing radiofrequency ablation of the renal tumor .

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various etiologies of cutaneous horn reported in literature till date111213 though cutaneous horns have been described in the literature for many years , they still remain novel to many clinicians especially when located in unusual areas like the genitalia . they usually appear in uncovered areas and/or from constant irritation over the scalp or face . it resembles the horn of an animal but has no bony structure inside . despite the typical appearance of cutaneous horn , there can be a wide range of pathology at the base ranging from benign , premalignant to malignant changes . a 47-year - old man presented with a raised painless growth over the prepuce for the last 4 months . twelve years ago , he was diagnosed with testicular seminoma of the right side . the tumor was excised , and six cycles of cisplatin - based chemotherapy were given . physical examination revealed a solitary , firm , nontender and well - circumscribed horn - like projection over the prepuce at 2 o clock position [ figure 1 ] . a clinical diagnosis of the penile cutaneous horn was considered , and a punch biopsy was performed . clinical image of cutaneous horn over the prepuce histopathological examination showed a raised lesion in the epidermis with hyperkeratosis , mounds of parakeratosis , focal hypergranulosis and marked irregular acanthosis with elongated [ figure 2 ] and inwardly curving rete pegs that enclosed several cavernously dilated thin - walled blood vessels within the papillary dermis [ figure 3 ] . a few of these blood vessels toward the base of the lesion showed fibrin thrombi . photomicrograph showing hyperkeratosis , papillomatosis , acanthosis and blood filled cavernous vessels in the papillary dermis ( h and e , 4 ) photomicrograph showing hyperkeratosis , papillomatosis and marked acanthosis with inwardly bending broad rete pegs enclosing cavernous blood vessels with fibrin thrombi ( h and e , 4 ) a diagnosis of solitary angiokeratoma presenting as the cutaneous horn was established based on the clinical presentation and histopathological findings . cutaneous horn ( cornu cutaneum ) is a clinical entity that appears as a conical protuberance over the skin surface and resembles a minuscule animal horn . they are of different shapes and sizes and can have satellite horns . by definition , it is a circumscribed conical markedly hyperkeratotic lesion in which the height of the keratotic mass amounts to at least half of its largest diameter . on the other hand , angiokeratoma has a pleomorphic appearance varying from papules , nodules , plaques which may be single or multiple . of the many clinical variants , solitary angiokeratoma represents an acquired disorder presenting as single warty papule . solitary angiokeratoma presenting as the cutaneous horn is a rarity , scarcely described in the literature . cutaneous horn could develop on a variety of skin conditions which can be benign , premalignant or malignant [ table 1 ] . a study analyzing 643 cases histopathologically had reported the most common causes for cutaneous horns to be benign ( 61.1% ) , followed by premalignant ( 23.2% ) and malignant ( 15.7% ) in that order . it was based on clinical appearance , apparent causation and histology [ table 2 ] . montgomery 's classification as of today , there is no precise clinical information to make a distinction of benign or malignant etiology for a cutaneous horn . in general , clinical pointers toward malignancy they are usually larger and harder at their base due to inflammation and are present at unusual sites such as genitalia . the presence of a malignancy elsewhere in the body supports the probability of cutaneous horn to be malignant . it is important to know the primary pathology which has led to the cutaneous horn to rule out malignancy and to direct prospective further therapy . the present case report highlights the presence of a solitary angiokeratoma as cutaneous horn over the prepuce , which has not been reported before . the present case report highlights the presence of a solitary angiokeratoma as cutaneous horn over the prepuce , which has not been reported before . the present case report highlights the presence of a solitary angiokeratoma as cutaneous horn over the prepuce , which has not been reported before .

we present a case of a 47-year - old man with 4 months history of conical growth on the prepuce with a progressive increase in size . the patient had been treated for seminoma a decade ago . histopathology of the growth showed features of angiokeratoma . it is unusual for angiokeratoma to masquerade as a cutaneous horn .

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paget 's disease is a chronic bone disorder characterized by focal areas of excessive osteoclastic resorption accompanied by a secondary increase in osteoblastic activity , resulting in abnormal bone structure , bone expansion , and deformity . scintigraphy using either tc99m - methylene diphosphonate or fluorine-18 ( f-18 ) fluoride is the most useful method of detecting pagetic lesions . we report the imaging findings of a patient with paget 's disease in carcinoma lung who underwent during staging and follow - up imaging using f-18-fluorodeoxyglucose ( fdg ) positron emission tomography / computed tomography ( pet / ct ) . a 65-year - old male patient diagnosed to have right lower lobe lung adenocarcinoma was referred for fdg pet / ct for staging evaluation . fdg pet - ct showed intense tracer uptake in the right lower lobe lung lesion along with multiple mediastinal and right supraclavicular lymph nodes [ figure 1 ] . furthermore , increased tracer uptake noted in the entire left hemipelvis with a maximum standardized uptake value ( suvmax ) of 5.3 . ct showed cortical thickening , intra trabeculation with course thick trabeculae , bone expansion , and multiple areas of sclerosis , consistent with paget 's disease [ figure 2 ] . he underwent follow - up fdg pet - ct after three cycles of chemotherapy showed intense fdg uptake with decrease in size and metabolism of the lung primary and mediastinal nodes with complete response in supraclavicular and some mediastinal nodes . but left hemipelvis uptake remains same , and he was asymptomatic for paget 's disease [ figure 3 ] . whole body fluorodeoxyglucose - positron emission tomography/ computed tomography ( fdg pet / ct ) maximum intensity projection image showing primary right lower lobe lung mass and mediastinal , right supraclavicular nodes . furthermore , diffuse increased uptake in left hemipelvis noted ( paget 's disease ) axial computed tomography of the pelvis showing left ilium cortical thickening , intra trabeculation with course thick trabeculae , bone expansion , and multiple areas of sclerosis , consistent with paget 's disease whole body fluorodeoxyglucose - positron emission tomography/ computed tomography ( fdg pet / ct ) maximum intensity projection image showing decrease in primary right lower lobe lung mass and mediastinal nodes . paget 's disease is a disorder of unknown etiology with unevenly increased osteoclastic and osteoblastic skeletal remodeling . bone involvement may be monostotic or polyostotic with characteristic radiographic features of osseous enlargement , deformity , and trabecular thickening . there is a rise in serum alp and abnormal remodeling of bone , leading to characteristic radiograph appearances of cotton wool appearance of the skull , ivory vertebra , and blade of grass shape in long bones . fdg - pet is a tomographic technique , with superior spatial resolution compared with a bone scan , with the added ability to quantitatively measure ( suvmax ) disease activity , and monitor the response to treatment . the role of fdg - pet in paget 's disease is not as yet well - elucidated . it is unclear whether paget 's disease may lead to false - positive findings in oncological patients , or if fdg - pet can reliably differentiate benign pagetoid changes from metastatic and sarcomatous changes of bone . some studies have concluded that paget 's disease is not associated with fdg uptake in most of the cases , but fdg uptake may be seen in patients with more active disease . previous reports of increased tracer uptake in paget 's disease mimicking metastasis ina case of malignant mesothelioma and rectal cancer have been reported . we describe a case of increased fdg activity in pagetoid pelvis in lung cancer patient detected incidentally using pet / ct . the intense fdg focal uptake in the left hemipelvis lesion on fdg - pet in our case is a possibility of false positive findings in patients with cancer . fused pet / ct images can add increased specificity in the characterization of an osseous lesion when compared with stand - alone pet by differentiating between the exact location of fdg uptake in these lesions . in general , cortical distribution of fdg uptake is more frequently seen in paget 's disease , and a medullary distribution of fdg uptake is more often associated with osseous metastases . computed tomography correlation may often improve the diagnostic accuracy of nonspecific fdg uptake in some patients , with the potential for discriminating between benign paget 's disease and associated sarcomas . coregistered pet / ct data may obviate the need for further evaluation or biopsy , as in our case , especially when ct scan findings are characteristic for paget 's disease . follow - up imaging was helpful as lung primary and nodes were responding to the chemotherapy but the pelvic lesion remains same confirming unrelated to lung cancer as paget 's disease of pelvis .

paget 's disease of bone is a benign disease , of uncertain etiology , characterized by an accelerated turnover , that is , bone resorption and formation . paget 's disease may be present in up to 5% of the population , and the majority of cases are asymptomatic . we report the imaging findings of paget 's disease of pelvis discovered incidentally in patient with lung cancer evaluated by fluorine-18-fluorodeoxyglucose ( fdg ) positron emission tomography / computed tomography ( pet / ct ) for staging . fdg pet - ct scan showed intense uptake in the right lung lower lobe primary and mediastinal lymph nodes . furthermore , increased uptake noted in left hemipelvis suggestive of paget 's disease . he underwent follow - up fdg pet - ct after chemotherapy showed decrease in lung mass and mediastinal nodes . however , the uptake in left hemipelvis remains same confirming paget 's disease .

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one of those subtypes is immunoglobulin d multiple myeloma which can have different clinical presentations . advancement in the treatment of immunoglobulin d multiple myeloma is promising and should lead clinicians to earlier diagnosis for better outcomes . a 53-year - old caucasian male patient with previous medical history of anaplastic oligodendroglioma status post - surgical removal and temozolomide therapy for 1 year in 2006 presented to the outpatient clinic on september 2013 complaining of back pain while mowing the lawn . pain was described as severe and sudden and limiting the ability of regular daily activity . his family history is significant for ovarian cancer in his mother and coronary artery disease in his father . physical examination showed tenderness over the lower thoracic vertebrae with no sensory or motor impairment . his neurological examination including gait assessment was normal . initial lab investigations showed low hemoglobin of 12.5 g / dl ( reference range 13.217.1 g / dl ) , normal vitamin d 25-oh of 47 ng / ml ( reference range 30100 ng / ml ) , high calcium level of 10.5 mg / dl ( reference range 8.610.3 mg / dl ) , and low parathyroid hormone of 5 pg / ml ( reference range 1065 pg / ml ) his creatinine was normal at 1.08 mg / dl ( reference range 0.701.33 mg / dl ) , and he had mildly elevated alkaline phosphatase of 128 u / l ( reference range 40115 u / l ) . aspartate aminotransferase and alanine aminotransferase were both within normal limits . serum protein electrophoresis showed total protein was normal at 6.9 g / dl ( reference range 6.18.1 g / dl ) , normal albumin at 4.0 ( reference range 3.54.7 g / dl ) , normal alpha 1 globulins , alpha 2 globulins , beta globulins , and gamma globulins , and showed an abnormal protein band in the gamma globulin region . urine electrophoresis showed normal 24-hour creatinine of 2.37 g ( reference range 0.632.50 g/24 h ) elevated total 24-hour protein of 3,050 mg ( reference range < 150 mg/24 h ) , elevated protein - to - creatinine ratio , and two abnormal protein bands detected in the gamma globulin region . free light chain assay showed serum free kappa elevated at 3,090.0 mg / l ( reference range 3.319.4 mg / l ) and low free lambda of 1.8 mg / l ( reference range 5.726.3 mg / l ) , and free kappa / lambda ratio was elevated at > 1,000.00 ( reference range 0.261.65 ) . immunoglobulin d was elevated at 566.0 mg / dl ( reference range < 15.3 mg / dl ) . magnetic resonance imaging ( mri ) of thoracic spine with and without contrast showed acute pathological fracture of the t12 vertebral body with enhancing soft tissue which extends into the left ventral epidural space and left t11t12 neural foramen . bone marrow biopsy was obtained and showed 60% cellularity with about 54% cellularity consistent with atypical plasma cells with normal male karyotype . fluorescent in situ hybridization was positive for gain of 11q ; however , there was normal appearance of 11;14 . mri of thoracic spine with and without contrast because of worsening back pain 2 weeks later showed a new t8 fracture ( fig . he received a total of 6 cycles and his kappa light chain was down to 3.96 mg / l ( reference range 3.319.4 mg / l ) and his immunoglobulin d level was 0.7 mg / dl ( reference range < 15.3 mg / dl ) . he also received 9 treatments of high - dose radiation therapy to his thoracic spine for pain control . after his fifth cycle , he was referred to a tertiary center for assessment of autologous peripheral blood stem cell transplant , which he underwent 6 months after the initial diagnosis . follow - up after 6 months of the transplantation showed complete remission , and the patient agreed to continue on lenalidomide maintenance therapy for a total of 3 years or as long as he is in remission . immunoglobulin d multiple myeloma is a rare disease with an incidence of 2% in all myelomas . the main presenting features of immunoglobulin d myeloma were bone pain , fatigue , and weight loss . a previous review of 77 cases reported bone pain as the most common presenting symptom , which happened in 77% of the cases with 89% lambda light chain predominance . median age of presentation was 57 years . though previously immunoglobulin d multiple myeloma was thought to have poor prognosis overall , a recent study reported median survival of 51.5 versus 50.7 months for patients with other subtypes . our case is peculiar as it represents a rare disease presenting in a young male patient with no identifiable risk factor . indeed , it shows excellent response to the standard chemotherapy used in multiple myeloma and to autologous peripheral blood stem cell transplant , which was done after complete remission . previous reports of combining chemotherapy and autologous peripheral blood stem cell transplant showed improvement in prognosis in this rare disease . immunoglobulin d multiple myeloma can present as spontaneous fracture as initial presentation and it usually happens in young males . advancement in the treatment of immunoglobulin d multiple myeloma urges clinicians to offer their patients new treatment options . the authors declare that there is no conflict of interest regarding the publication of this paper .

immunoglobulin d multiple myeloma is a rare type of multiple myeloma that usually presents as bone pain , fatigue , or weight loss . we report a case of immunoglobulin d multiple myeloma in a 53-year - old caucasian male patient with previous medical history of anaplastic oligodendroglioma status post - surgical resection who was evaluated for back pain while mowing the lawn . his physical examination showed tenderness over the lower thoracic vertebrae with no sensory or motor impairment . initial lab investigations showed normocytic anemia and hypercalcemia with low parathyroid hormone . magnetic resonance imaging of thoracic spine with and without contrast showed acute pathological fracture of the t12 vertebral body with enhancing soft tissue which extended into the left ventral epidural space and left t11t12 neural foramen . serum protein electrophoresis showed abnormal protein band in the gamma globulin . free light chain assay showed serum free kappa which was elevated at 3,090.0 mg / l ( reference range 3.319.4 mg / l ) . immunoglobulin d was elevated at 566.0 mg / dl ( reference range < 15.3 mg / dl ) . the patient was successfully treated with standard chemotherapy and autologous peripheral blood stem cell transplant with complete remission 3 years after starting treatment . advancement in the treatment of immunoglobulin d multiple myeloma urge clinicians to offer their patients new treatment options especially as of the earlier presentation of this subtype of multiple myeloma and the previous reports of worse prognosis .

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the incidence of neuroendocrine tumors is increasing ( approximately 6% per year ) , but clinical presentation is nonspecific , resulting in delays in diagnosis ( 5 - 7 years ; approximately 70% have metastases ) . neuroendocrine tumors usually exist at the lung , stomach and colon , but the small bowel is a rare location . we present an unusual case of small bowel neuroendocrine malignant tumor diagnosed by double - balloon enteroscopy ( dbe ) . the capsule was stuck in the jejunum stricture and was removed with a snare under dbe . a 36-year - old man with weight loss presented with a 1-year history of distention , abdominal pain and macies . capsule endoscopy found segmental distribution of ulceration , erosion and nodal hyperplasia in the proximate jejunum consistent with crohn 's disease ( fig . 1a ) . neither the doctor nor the patient remembered finding the capsule in the stool . when the scope passed 20 cm from the treitz ligament we found jejunum erosion , nodal hyperplasia , stenosis ( fig . the dbe was inserted again for biopsy , and some specimen were retrieved . the next day , barium examination revealed that the stenosis was near to the treitz ligament ( fig . capsule retention is defined as the presence of the capsule endoscopy in the digestive tract for a minimum of 2 weeks after ingestion or the capsule being retained in the bowel lumen indefinitely unless a targeted medical , endoscopic , or surgical intervention is initiated . small bowel stenosis often leads to capsule retention . in this patient , we shared an examination process of a rare case of neuroendocrine malignant tumor in the small bowel . as the capsule endoscopy was stuck in the narrow parts , the lesion images from different angles were shot at different times , which led us to mistake for multiple lesions and to make a misdiagnosis of crohn 's disease . if we had adopted the therapeutic regimen in accordance to the diagnosis of crohn 's disease , maybe the patient would have lost the chance of operation . at the same time , we introduced the skills that the application of dbe could be used in the removal of capsule retention .

the diagnosis of neuroendocrine malignant tumor in the small bowel is difficult [ j oncol 2008;2008:212067 ] . it is usually found intraoperatively during intestinal resection and confirmed by subsequent histological examination . we reported a case of jejunum neoplasm which was misdiagnosed as crohn 's disease by capsule endoscopy . capsule endoscopy was stuck in the jejunum stricture and was removed with a snare under double - balloon enteroscopy . the pathology of the biopsy was jejunum small cell malignant carcinoma tending to neuroendocrine malignant tumor . the immunohistochemical result revealed that cd99 and ki-67 were positive . the patient underwent intestinal resection and the diagnosis of neuroendocrine malignant tumor was confirmed .

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creutzfeldt - jakob disease(cjd ) is a subacutely progressive neurological disorder caused by deposition of prion proteins in brain . it is a very rare entity and the world - wide incidence is 0.5 - 1.0 cases per million per year . a majority of cases are sporadic , some cases are familial , carrying a prion protein mutation and it is usually fatal within 1 year . we report the significance of mri findings to correlate and support the clinical diagnosis of cjd . a 75 year - old lady presented with rapid cognitive decline of three months duration . a patient was evaluated as a case of dementia and had frontal , parietal , temporal , and occipital deficit signs on neuro - psychiatry evaluation . mri was done as a part of her investigation on a 1.5 t ge ( signa , usa ) scanner , which showed diffuse cortical t2 and flair hyperintensities in bilateral frontal , parietal , temporal , and occipital locations [ figures 1 and 2 ] . the cortical hyperintensities showed significant restriction on dwi [ figure 3 ] , giving rise to the strikingly conspicuous lesions compared to the normal cortex signal in the above locations . axial t2 w mr images showing faint and equivocal cortical hyperintensities ( arrows ) in bilateral frontal , parietal , and temporal lobes . axial flair mr images shows the signal abnormalities slightly better compared to figure 1 , although cortical hyperintensities ( arrows ) are not very striking . diffusion weighted mr images clearly shows increased visibility of high signal from restricted diffusion ( arrows ) in the bilateral frontal , parietal , temporal , and occipital regions along the cortical locations . later in the course of the disease , she developed myoclonic jerks , eeg changes which were consistent with the who criteria of probable cjd . according to the national cjd registry at nimhans , bangalore , india , there are only 85 recorded cases of cjd till september 2005 . the diagnostic triad of cjd i.e. , of a progressive dementia , myoclonus and periodic sharp wave eeg activity may not be evident in about 25% of the cases . mri with dw and flair sequences is an invaluable modality in supporting the diagnosis of cjd . shiga et al in his study concluded that diffusion - weighted mri(92% ) had higher sensitivity in the detection of cjd than flair sequences ( 41 - 59% ) , t2 ( 36 - 50% ) , eeg ( 50 - 78% ) , csf protein 14 - 3 - 3(84% ) or neuron specific enolase ( 73% ) . diffusion - weighted mri is more resistant for motion artifacts than t2w and flair images . the abnormalities on dw - mri could be detected as early as at 3 weeks of symptom duration and even before the appearance of periodic triphasic waves on eeg . matoba et al noted that the hyperintensity in the basal ganglia and cortex during the early stages was more extensive and conspicuous while in the later stages there was disappearance of the abnormal signals in the cortex . the cause for restricted diffusion is attributed to accumulation of abnormal vacuoles in the cytoplasm and microvacuolation of neuritic process heralding spongiform degeneration . sporadic cjd shows t2 prolongation and restricted diffusion in the corpus striatum followed by the neocortex and posterior and medial thalami . in variant - cjd , the t2 hyperintensities are commonly located in the posterior ( pulvinar ) and medial thalami followed by periaqueductal grey matter , striatum , and less commonly in the neo - cortex . the increased signal intensity in the pulvinar relative to the anterior putamen is called the pulvinar sign is the most sensitive marker for variant cjd . the bilateral pulvinar sign has a sensitivity of 78% and correlates with the histological gliosis . the combination of flair and dw imaging has a sensitivity , specificity and accuracy of over 90% in differentiating cjd from other dementias . the multifocal cortical and subcortical hyperintensities in the grey matter showing restricted diffusion on mri may be more useful than the csf protein 14 - 3 - 3 analysis . 14 - 3 - 3 protein analysis was not performed because of the lack of the availability of the test at our institute . csf protein 14 - 3 - 3 analysis availability is limited only to a few cities and is not done routinely in all the hospitals . however , diagnosis can only be confirmed by histological examination of brain tissue obtained either by the brain biopsy or after autopsy . these are not performed by many institutions due to the transmissible nature of the disease . this case highlights the role of dw - mri as practical modality in the early diagnosis of cjd . mri radiologist can give the first clue to an unsuspected case of cjd , as in this case and can make it easy for the clinician who has to do an elaborate work - up of dementia cases . radiologists and neurologists should be familiar with the characteristic appearance of dw imaging as a clue to the diagnosis of this dreaded disease , for which no treatment is available till date . in a patient with rapid dementia , mri should be done as it is accurate , noninvasive , and cost - effective ( as compared to csf-14 - 3 - 3 analysis ) and if findings are suggestive of cjd , the clinician should be alarmed and appropriate infection control measures are to be taken .

we describe a case report where the diagnosis of sporadic creutzfeldt - jakob disease(cjd ) was suspected by the magnetic resonance imaging ( mri ) radiologist in a 75-year - old lady who presented with rapid cognitive decline . mri revealed cortical t2 and flair(fluid attenuation and inversion recovery ) hyperintensities in bilateral fronto - parietal and temporo - occipital locations and showed significant restriction on diffusion - weighted images(dwi ) . in this case report , we discuss the role of mri to suspect the diagnosis of cjd in appropriate clinical settings .

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a 33-year - old female patient presented at the emergency room with epigastric pain , nausea , and vomiting that had persisted for a day . the patient had a history of child birth eight months prior , and had proximal deep vein thrombosis ( dvt ) on the left common femoral vein during the 36th week of pregnancy . an inferior vena cava ( ivc ) filter had been inserted instead of anticoagulation due to the high risk of bleeding during pregnancy . removal of the ivc filter was recommended one month after insertion , but the patient refused for personal reasons . on arriving at the emergency room , her vital signs were stable and the laboratory examination did not show abnormalities other than mild leukocytosis . the patient 's prothrombin time international normalized ratio value at the emergency room was 1.31 due to irregular intake of warfarin . a computed tomography ( ct ) scan revealed that one of the ivc filter legs had penetrated the ivc wall and caused a duodenal perforation ( fig . a protruding ivc filter leg was observed in the lumen of the third portion of the duodenum ( fig . 2 ) . in addition , the duodenum mucous membrane on the opposite side showed erythema , erosion , and nodular changes , resembling chronically progressing penetration . an emergency laparotomy was performed in order to remove the ivc filter and to repair the duodenum . because there were concerns regarding the possible ivc rupture during surgery , a cannula was placed in the superior vena cava to provide extracorporeal circulation when needed . also , the femoral artery and femoral vein were isolated for cannulation . the portions of the ivc and the duodenum , including the penetrations , were isolated behind the colon . when the duodenum was lifted up , we found the ivc filter leg between the ivc and the duodenum . we then cut the ivc filter leg and removed the ivc filter leg remnant from the duodenum portion . the ivc was found to be densely adhered to the surrounding tissue including the aorta , and fixed to the adjacent structures . we concluded that isolation and removal of the ivc filter leg remnant in the ivc were more dangerous due to the risk of rupture . the remaining leg protruding from the ivc side to the duodenum was cutoff and removed ( fig . 3 ) . after the surgery , ileus occurred and the patient started to eat by mouth after 14 days . the ivc filter is known as an effective and safe method for preventing fatal pulmonary thromboembolism in patients with deep vein thrombosis . the ivc filter is indicated in dvt patients when any of the following symptoms are present : contraindication of anticoagulation , major bleeding , need for surgery within 2 weeks , severe and prolonged thrombocytopenia , and recurrent dvt disease despite anticoagulation . complications related with the ivc filter can be categorized as insertion - related complications , device failure , and late complications . insertion - related complications include pneumothorax , hemorrhage , filter misplacement , excessive tilt , and vascular injury . late complications include recurrent pulmonary embolus , caval occlusion , filter migration , and filter leg perforation . the titanium greenfield filter showed a 3.5% perforation rate , the stainless steel greenfield filter showed a 4.4% rate , the bird 's nest filter showed a 38% rate , and the simon nitinol filter showed a 37% rate . most patients with perforations do not show any symptoms and the perforation rarely causes clinical problems . however , there are cases where the filter can damage surrounding organs and cause severe complications in the aorta , duodenum , ureter , or retroperitoneal space [ 4 - 6 ] . pulsation of the aorta and respiratory motion are thought to be the main cause of caval penetration of the filter leg . in our case , the cause of the ivc wall penetration seemed to be chronic progression of the ivc filter leg , nine months after the ivc filter insertion ; subsequently , it finally penetrated into the duodenum . based on the preoperative ct venography , the ivc flow was maintained and there was no dvt below the ivc level . also , based on the observations in the operation room , although cardiopulmonary bypass was in standby before surgery , removal of the ivc filter was thought to be more risky . thus , a partial resection of the ivc filter leg that was penetrating the duodenum was performed , and the ivc was reinforced . currently , the ivc filter is widely used and only 50% of them are removed from patients . most of the remaining ivc filters are asymptomatic and do not cause clinical problems . however , in order to prevent potential sequelae caused by ivc filter leg penetration , like that reported in this case , the removal of the ivc filter , when possible , is preferred .

the inferior vena cava ( ivc ) filter is known as an effective and safe method for preventing fatal pulmonary thromboembolism in patients with deep vein thrombosis . usually , the remaining ivc filters are asymptomatic and do not cause clinical problems . we report a case of duodenal perforation caused by a remaining ivc filter .

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a detailed description of patients with history of recurrent respiratory infections and progressive renal failure was given 1979 . the case under discussion has various rare features like young age of the patient , associated glomerulopathy causing nephrotic syndrome and normal renal function , which is showing gradual deterioration . normal renal function at the time of diagnosis is known and in one large series published by bhandari et al . an 8-year - old male child presented with a history of facial puffiness and edema of one year duration . he was diagnosed to have nephrotic syndrome and was treated by a local physician with steroids . he did not improve , however , and was referred to this hospital for further management . there was no history of drug ingestion including exposure to mycotoxins or other herbal medicines . patient had stunted growth with moon facies , secondary to steroids and had clinical features of rickets . his investigations revealed hemoglobin of 10 g / dl , blood urea 33 mg / dl and serum creatinine 0.7 mg / dl . he was human immunodeficiency virus non - reactive and hepatitis b surface antigen and hepatitis c virus and 24 h urine protein was 3565 mg / dl . complete urine examination showed 2 + albumin , 4 - 6 red blood cells and granular casts . he was started on cyclophosphamide . however , there was no response even after 6 months . biopsy showed 23 glomeruli , four of whom showed segmental sclerosis [ figure 1 ] . segmental glomerulosclerosis ( thin arrow ) and karyomegaly in tubular cells ( thick arrow ) ( h and e , 400 ) karyomegaly in tubular epithelial cells ( h and e , 400 ) ( a ) segmental sclerosis and tubular atrophy ( periodic acid schiff , 200 ) . ( b ) tubular atrophy and interstitial inflammation ( h and e , 200 ) . ( c ) interstitial fibrosis ( masson 's trichrome , 200 ) immunohistochemical stains for bk virus and cytomegalovirus were negative . he is under regular follow - up and his last creatinine has increased to 1.2 mg / dl . kin is a rare disorder characterized by enlarged tubular epithelial cell nuclei and chronic interstitial nephritis . histologically , presence of interstitial nephritis along with karyomegaly in the tubular epithelial cells is characteristic of this disorder . karyomegalic cells have been identified in various tissues like astrocytes , schwann cells , intestinal smooth muscle and bile duct epithelium . mcculloch et al . , reported kin in three adolescent patients treated with ifosfamide for ewings sarcoma . a familial clustering is known and frequency of human leukocyte antigen ( hla)-a9 and hla - b35 haplotypes suggest the possibility of genetic susceptibility . another genetic defect on chromosome 6 , linked to major histocompatibility complex locus is also suspected . the morphological alterations in renal epithelial cells are thought to be the initial damage caused by either chemicals or viral agents , which in susceptible individuals lead to disruption of cells . immunofluorescence and histological findings are negative in a large series presented by bhandari et al . in contrast our case clinically presented with nephrotic syndrome and also had histological evidence of focal segmental glomerulosclerosis ( fsgs ) . as there is no positive family history or drug history and exposure to toxins , it is important to diagnose this entity as it is a progressive disorder leading to irreversible renal damage . common etiological factors for both these lesions are toxins and drugs , patient on repeated questioning denied any history of drug or herbal medicine intake . there is no history of renal disease in the family and it unlikely to be familial because the chromosomal abnormalities described are different for both . spoendlin et al . , reported four patients who were asymptomatic initially , but later experienced progressive renal failure . this particular case under discussion also initially presented with normal renal function and on follow - up was showing gradual deterioration . we present a rare case of kin who initially presented with normal renal parameters ; interestingly , this patient 's clinical presentation was of nephrotic syndrome whose biopsy also revealed fsgs . hence , we think that the patient has idiopathic fsgs with an incidental kin , which is known to occur sporadically .

karyomegalic interstitial nephritis ( kin ) is a rare form of , progressive chronic interstitial nephritis . we present a case of kin in a child , who was also found to have nephrotic syndrome because of focal segmental glomerulosclerosis on renal biopsy . to our knowledge , this is the first case of kin associated with glomerulopathy .

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as a national reference center for q fever , our center receives samples from france and other regions for serologic , molecular , histologic , and immunohistochemical analyses as described ( 57 ) . in 2012 , we received a cardiac valve sample from a patient in cayenne with q fever endocarditis who had undergone surgery in martinique . in the same year , we collected 4 heparinized blood samples from patients with acute q fever from cayenne that were collected before initiation of antimicrobial drug treatment . serologic titers of igg1 increased to 51,200 in this patient , and results of quantitative pcr ( qpcr ) and immunohistochemical analyses of the valvular sample were positive for c. burnetii ( figure 1 ) . the other 4 patients ( 2 men and 2 women ) had fever and acute pneumonia , and 2 of them also had increased transaminase levels . the heparinized blood samples were tested by using a specific qpcr ; samples from only 1 patient were positive for c. burnetii . immunohistochemical detection of coxiella burnetii in resected cardiac valve of a 60-year - old man with q fever endocarditis , cayenne , french guiana . we successfully cultured c. burnetii from the valvular sample after incubation for 16 days and from 3 blood samples after incubation for 25 , 32 , and 32 days . paradoxically , the only blood sample that was positive by qpcr was negative by culture . spacers cox 51 and cox 20 were the most discriminating spacers in identifying this genotype , and the 3 isolates from the blood cultures were also identified by these 2 spacers as genotype 17 ( figure 2 ) . this genotype had been identified in our laboratory only once , in 2000 in an aortic valve of a 40-year - old french man who had undergone surgery in france , had q fever endocarditis , and was co - infected with streptococcus oralis . retrospectively , we found that patient had lived in cayenne for years before his diagnosis with q fever endocarditis . therefore , all genotype 17 isolates were obtained from who lived or had lived in cayenne , making it unique to this area . we determined the antimicrobial drug susceptibilities of these isolates , and the mic of doxycycline was 0.25 g / ml for all isolates ( 10 ) . phylogenetic diversity of 34 genotypes of coxiella burnetii identified by using multispacer sequence typing ( mst ) . scale bar indicates nucleotide substitutions per site . for the past 10 years , routine cell culture for c. burnetii has been performed in our laboratory . we found that the proportion of isolates obtained from blood samples of patients with acute q fever was higher for patients from cayenne than for patients from metropolitan france . we obtained 3 isolates from 5 blood samples from untreated patients in cayenne and 3 isolates from 65 samples from patients in metropolitan france ( p = 0.003 , by fisher exact test ) . however , we did not find any difference with respect to the culture delay between patients from the 2 locations . our work shows that genotype 17 , a unique genotype , is circulating in cayenne . this genotype is related to genotypes that harbor the qph1 plasmid , which causes the most severe clinical forms of acute q fever in experimental animal models ( 11,12 ) . only bacteria from this group and bacteria containing the qpdv plasmid have been found in cases of human acute q fever ( 9,13 ) . we believe that severity of q fever infection is related to the strain of c. burnetii circulating in cayenne . because the population in french guiana is a large diversity of creole , amerindian , maroon , caucasian , and asian persons ( 14 ) , we excluded the hypothesis that genetic susceptibility of patients from cayenne to c. burnetii infection might be related to severity of the disease . we observed a higher rate of strain isolation from the blood of patients from cayenne than from the blood of patients from metropolitan france . this difference may be related to a higher bacterial load in blood or a greater ability of the bacteria to grow on cell cultures . this second hypothesis seems more likely because even if the observed delay for the first culture was the same for genotype 17 and other genotypes , the strain from cayenne was isolated more frequently in the cell line that we used ( hel cells ) than other strains of c. burnetii from france . in addition , we did not find a higher number of dna copies in the blood of patients from cayenne , and qpcr results were not correlated with culture results . c. burnetii isolates from cayenne were susceptible to antimicrobial drugs , particularly doxycycline . these isolates cause acute pneumonia and endocarditis . among the 34 genotypes identified in our study by multispacer a larger biodiversity of strains has been observed in samples from patients in metropolitan france ( 9 ) , where 21 genotypes circulate ( figure 2 ) . in contrast , during the recent q fever outbreak in the netherlands , it appears that a single strain ( genotype 33 ) was responsible for the epidemic ( 15 ) . we believe that there has been an epidemic developing in cayenne since 1996 that is caused primarily , if not solely , by a single strain that has circulated since at least 2000 , whose reservoir is unknown ( 1,2 ) . in conclusion , c. burnetii genotype 17 is circulating in french guiana and causing acute infections and endocarditis . this strain is epidemic and most likely causes more acute infections with exacerbated immune responses than other known genotypes of c. burnetii .

acute q fever is an emergent and severe disease in french guiana . we obtained 5 coxiella burnetii isolates from samples of patients from cayenne and found an epidemic clone circulating in cayenne . this clone has caused pneumonia and endocarditis and seems to be more virulent than previously described strains .

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. an earlier version of this paper was written as part of charlotte khlbrandt 's msc dissertation project at the london school of hygiene and tropical medicine . ck conducted the literature review , collected and analysed the data , interpreted the results and drafted the paper . we would like to thank dr alex mold , who co - supervised the msc dissertation and commented on a draft of this paper . we are also grateful for the wellcome trust 's commitment to cover open access charges . . an earlier version of this paper was written as part of charlotte khlbrandt 's msc dissertation project at the london school of hygiene and tropical medicine . ck conducted the literature review , collected and analysed the data , interpreted the results and drafted the paper . we would like to thank dr alex mold , who co - supervised the msc dissertation and commented on a draft of this paper . we are also grateful for the wellcome trust 's commitment to cover open access charges .

light therapy is still used to treat a number of common diseases in russia . the practice is firmly anchored in history : soviet clinical practice was divorced from the emerging field of evidence - based medicine . medical researchers were cut off from international medical research and scientific literature , with much soviet scientific activity based on a particular socialist ideology . in this study , the use of light therapy serves as a case study to explore tensions between international evidence - based medicine and practices developed in isolation under the soviet union , the legacy of which is to the detriment of many patients today . we used four different search methods to uncover scientific and grey literature , both historical and contemporary . we assessed the changing frequency of publications over time and contrasted the volume of literature on light therapy with more orthodox treatments such as statins and painkillers . our search found an increasing number and comparatively large body of scientific publications on light therapy in the russian language , and many publications emanating from prestigious russian institutions . combined with our analysis of the historical literature and our appraisal of 22 full text articles , this leads us to suggest that light therapy entered mainstream soviet medical practice before the stalinist period and still occupies an important position in contemporary russian clinical practice . we propose that this outdated treatment survives in russia in part due to the political , economic and social forces that helped to popularize it during soviet times , and by the seeming justification offered by poorly executed studies .

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different factors , especially genetic , effect individual attitude to regular physical activity in iranian traditional medicine . our aim was to conduct a comparative revision and evaluation of the effect of genetic factors on physical activity in classic medicine and iranian traditional medicine . in this study , we reviewed persian resources in the research center of traditional medicine at shiraz university of medical sciences . we also evaluated the texts on physical activity and genetics in pubmed and google scholar . the results of classical medicine revision showed the effect of especial genes on obesity and sedentary behavior . it is also derived from iranian traditional medicine resources that physical activity and sedentary behavior is affected by individual mizaj . the results showed that those with hot and cold mizaj have different genetic potentials in sedentary behavior and physical activity . such categorization would be helpful in identifying illnesses due to sedentary life in special groups of people .

background : different factors , especially genetic , effect individual attitude to regular physical activity in iranian traditional medicine . it was believed that individual physical activity attitude is affected by mizaj too . our aim was to conduct a comparative revision and evaluation of the effect of genetic factors on physical activity in classic medicine and iranian traditional medicine.methods:in this study , we reviewed persian resources in the research center of traditional medicine at shiraz university of medical sciences . we also evaluated the texts on physical activity and genetics in pubmed and google scholar.results:the results of classical medicine revision showed the effect of especial genes on obesity and sedentary behavior . it is also derived from iranian traditional medicine resources that physical activity and sedentary behavior is affected by individual mizaj.conclusion:the results showed that those with hot and cold mizaj have different genetic potentials in sedentary behavior and physical activity . such categorization would be helpful in identifying illnesses due to sedentary life in special groups of people . it would also allow designing dedicated treatment for each person .

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unicystic ameloblastoma ( ua ) was first described by robinson and martinez in 1977 as a special type of ameloblastoma . ua usually appears very similar to a non - neoplastic odontogenic cyst and is frequently clinically misdiagnosed as dentigerous cyst and odontogenic keratocyst hence , histological confirmation is mandatory from the management point of view . this report highlights the importance of clinical and radiographic features in the diagnosis and management of ua in a 5-year - old boy . a 5-year - old boy presented to our unit center for dental education and research , all india institute of medical sciences , new delhi , india with a painless hard swelling in the lower chin region of 3 months duration . swelling was found to be approximately 2 cm 2 cm in size , overlying skin was normal in color and texture with no evidence of sinus / fistula . swelling was non - tender , non - pulsatile , bony hard , non - fluctuant , non - compressible on palpation with expansion of both , buccal as well as lingual cortical plates and aspiration from the swelling yielded cystic color fluid . panoramic radiographic revealed that unilocular well - defined radiolucent lesion extending from lower deciduous first mandibular molar to right lower canine with evidence of roots resorption [ figure 1 ] . pre - operative panoramic radiograph showing radiolucent lesion in the right side of the mandible and resorption of the roots of the teeth on the basis of lingual cortical bone expansion , presence of cystic fluid on aspiration and evident of root resorption of the teeth in the panorex , we made the provisional diagnosis of ua . enucleation of the cyst with extraction of the involved teeth followed by application of carnoy 's solution for 3 min over the cavity was planned under general anesthesia ( ga ) . histopathology report of the specimen revealed that type 1 ua as per the histological criteria defined by ackerman et al . ( a ) discrete epithelial lines in a connective tissue stroma ( h and e , 10 ) , ( b ) discrete follicles with a similarity to the stellate reticulum of enamel with a varying quantity of connective tissue stroma.(h and e , 40 ) patient has been on regular follow - up since 2 years , patient is doing well with no signs of recurrence [ figure 3 ] . post - operative panoramic radiograph showing bone regeneration in the affected area and movement of tooth buds into the regenerated bone at 2 years follow - up period ameloblastoma is rare before the age of 10 years . according to statistical analysis of 1036 cases of ameloblastoma collected from the literature by small and waldron the ua is considered a variant of the solid or multicystic ameloblastoma , accounting for 6% to 15% of all intra osseous ameloblastomas . presence of lingual cortical plate expansion , cystic fluid on aspiration and presence of root resorption of teeth in panoramic radiograph helped us in making the preoperative diagnosis of ua over the dentigerous cyst without incisional biopsy ( which requires ga in the child ) . histopathological features of the tumor showed type 1 ( tumor confined to the luminal surface of the cyst ) ua as per the histological criteria defined by ackerman et al . treatment modality of ua is being divided into following types - enucleation alone yielded the highest recurrence rate among all treatments ( 30.5% ) . a more conservative approach is enucleation with application of carnoy 's solution and the extraction of closely related adjacent teeth has resulted in a recurrence rate of 16% . the success of the application of carnoy 's solution after enucleation was thought to be due to both its penetration and fixation action . the usual practice is to apply the solution with cotton applicators or ribbon gauze for 3 - 5 min , rinse the bony cavity . the recurrence rate could even lower than reported , if the closely related teeth with tumor are extracted . because in an attempt to preserve the tooth without damage , tumor remnants may be left around the tooth apex or root and these may lead to recurrence we carried out the same procedure in the case i.e. enucleation followed by application of carnoy 's solution for 3 min , extraction of all involved teeth and close follow - up . second surgery ( i.e. incisional biopsy followed by definitive treatment ) under ga in the child was not required due to proper preoperative planning of the case . at 2 years

unicystic ameloblastoma rarely seen in first decade of life . this tumour usually appears very similar to a non - neoplastic odontogenic cyst and is frequently clinically misdiagnosed as dentigerous cyst . the distinction from dentigerous cyst is important as unicystic ameloblastoma ( ua ) unlike dentigerous cyst needs different treatment approach and long term follow - up due to its chances of recurrence . this report highlights the importance of clinical examination in the diagnosis and management of ua in a 5 year old boy .

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macrolide , lincosamide and streptogramin b ( mlsb ) antibiotics are structurally different with a same mechanism of action . these drugs , especially clindamycin , are alternative drugs for some staphylococcus aureus infections such as skin and soft tissue infections particularly in penicillin - allergic patients ( 1 , 2 ) . clindamycin resistance in s. aureus strains may be either constitutive ( cmlsb ) or inducible ( imlsb ) . relapse of infection in a patient with s. aureus endocarditis was reported in 1976 ( 3 ) . detection of isolates with inducible clindamycin resistance is a problematic issue for the routine diagnosis , because they are erythromycin resistant and clindamycin susceptible in vitro and in the condition that they are not place adjacent to each other . in these cases , in vivo treatment with clindamycin may lead to clinical therapeutic failures ( 4 , 5 ) . the aim of this study was to determine the incidence of inducible clindamycin resistance in s. aureus isolates collected from clinical specimens in this geographic area . totally 162 s. aureus isolates were collected from clinical specimens of patients admitted to three university hospitals with 462 , 420 and 300 bed capacities in kerman , south - east of iran , from march 2011 to february 2012 . confirmation of s. aureus isolates and detection of methicillin resistant s. aureus ( mrsa ) were performed by phenotypic and genotypic methods as previously described ( 6 ) . only one isolate per patient this test was performed by placing an erythromycin ( 15 g ) disk ( mast , group ltd . , merseyside , uk ) at a distance of 15 to 20 mm from clindamycin ( 2 g ) disk ( mast , group ltd . , merseyside , uk ) on a mueller - hinton agar plate inoculated with 0.5 mcfarland standard bacterial suspensions . following overnight incubation at 37c , flattening of the clindamycin zone adjacent to the erythromycin disk ( d shaped ) indicated inducible clindamycin resistance ( 7 ) . from 162 s. aureus isolates tested for determination of inducible clindamycin resistance , 70 ( 43.2% ) were mssa and 92 ( 56.8% ) isolates were mrsa ( table 1 ) . sensitivity to both erythromycin and clindamycin was significantly higher in mrsa compared to mssa isolates . resistance to methicillin , erythromycin and clindamycin was observed in 92 ( 56.8% ) , 75 ( 46.29% ) and 46 ( 28.4% ) of the isolates , respectively . inducible resistance to clindamycin was determined in 14 ( 8.64% ) isolates ( d - test positive , figure 1 ) . table 2 shows the distribution of d - test positive s. aureus isolates in clinical specimens . among those , 11 ( 78.57% ) abbreviations : mssa , methicillin susceptible s. aureus ; mrsa , methicillin resistant s. aureus ; ery , erythromycin ; cli , clindamycin ; s , sensitive , r , resistant ; cmlsb , constitutive macrolide lincosamide and streptogramin b ; imlsb , inducible macrolide lincosamide and streptogramin b. data are presented as no . ( % ) . flattening of the clindamycin zone adjacent to the erythromycin disk produces a d shape . ( % ) . including : blood , skin and soft tissue , cerebrospinal fluid . clindamycin is an effective antibiotic agent used in the treatment of skin and soft - tissue infections caused by s. aureus isolates . this antibiotic has good tissue penetration , potential antitoxin effects , and also accumulates in abscesses ( 8) . however , resistance to clindamycin may develop in s. aureus isolates with inducible phenotype and these isolates have a high rate of spontaneous mutation which would enable these isolates to develop constitutive resistance to clindamycin during therapeutic process ( 4 ) . a positive d - test indicates the existence of inducible resistance to clindamycin . in this study 8.64% of 162 s. aureus isolates were d - test positive that is comparable with the findings of the studies by rahbar and hajia ( 9.7% ) ( 9 ) and sedighi et al . the prevalence of inducible and constitutive clindamycin resistance differs in different geographic areas ( 12 ) . in our study high number ( 46.29% ) of s. aureus isolates were resistant to erythromycin . among those , 14 ( 18.66% ) isolates had positive and 15 ( 20% ) had negative d - test results and 46 ( 61.33% ) were constitutive clindamycin resistance . in this study the prevalence of inducible and constitutive resistance to clindamycin in mrsa ( 11.95% and 47.8% respectively ) is higher than those in mssa ( 4.28% and 2.85% , respectively ) . the results of this study revealed that inducible resistance to clindamycin in s. aureus isolates is relatively high in this region . therefore , d - test should be performed to prevent treatment failures of s. aureus infections caused by the agents that are resistant to erythromycin and sensitive to clindamycin .

background : clindamycin is a frequently used antimicrobial therapeutic medicine used for the treatment of skin and soft tissue infections caused by staphylococcus aureus strains . resistance to this antibiotic is either constitutive or inducible . constitutive resistance to clindamycin could be detected by standard susceptibility testing methods . inducible clindamycin resistance could not be detected by in vitro routine tests . this type of resistance can be identified by d-test.objectives:the outbreak of inducible resistance to clindamycin in methicillin resistant and - susceptible s. aureus isolates were investigated in this study.materials and methods : totally 162 s. aureus isolates were evaluated for inducible clindamycin resistance by d - test in accordance with clinical and laboratory standards institute ( clsi ) guidelines.results:inducible clindamycin resistance was detected in 8.64% of s. aureus isolates . inducible and constitutive resistance to clindamycin was found to be higher in methicillin resistant s. aureus ( 11.95% and 47.8% respectively ) compared to methicillin susceptible s. aureus ( 4.28% and 2.85% respectively ) isolates.conclusions:our results showed that inducible resistance to clindamycin in s. aureus isolates is relatively higher in this region . therefore , d - test should be performed to prevent treatment failures against infections caused by s. aureus , which are resistant to erythromycin and the sensitive ones against clindamycin .

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kleine - levin syndrome ( kls ) is a rare disorder which mainly affects adolescent boys and characterized by recurrent episodes of hypersomnia , and sometime along with hyperphagia , behavioral and cognitive disturbances , and hypersexuality . several medications ( stimulants , lithium , valproate , antipsychotics , and antidepressants ) have been reported to provide variable benefit in different symptoms , with lithium being the most widely used drug . we are presenting a case of kls , who had complete remission with valproate and also reviewing the cases reported from india . a 17-year - old single male student of 12 standard , presented to our psychiatric outpatient clinic in september 2004 with hypersomnolence , low mood , decreased appetite and interest in studies , social and sexual disinhibition ( such as singing obscene songs loudly at home , and touching unconsenting females including mother 's body parts - limbs , face and genitalia ) . onset was acute , without any elicitable precipitating factor and course was episodic with average 7 - 10 days episode in every month for last 4 months and he maintained completely well in inter episodic period . provisional diagnosis of recurrent depressive disorder ( brief episodes ) was kept and he was started on sertraline ( 50 mg ) , on which he responded well . he remained asymptomatic for nearly 9 months , but started having similar episodes again from mid-2005 , due to which sertraline were gradually hiked up to 150 mg / day , but of no use . hence , he was admitted in our inpatient setting in march , 2006 for diagnostic evaluation and further management . after detailed evaluation , it was found that his sadness was not pervasive and depressive cognitions and associated disturbances were not present and hypersomnia remained predominant complaint as initially , he was sleeping 16 - 20 h / day . he was also not responding with these medications , hence differential diagnosis of kls versus depression was kept and later finalized to kls . his hemogram , renal functions , liver functions , blood sugar , routine urine , thyroid functions were within normal limits and chest x - ray , electrocardiography , electroencephalography ( eeg ) , and magnetic resonance imaging brain were normal . in view of good literature support lithium was started from 600 mg / day and hiked to 900 mg / day ( serum level 0.8 meq / l ) . on which he has shown significant improvement initially for 6 months , but later again started experiencing similar symptoms . he also had three episodes of fall , unresponsiveness and epileptiform discharge in eeg twice . hence , in view of seizure disorder and lack of response , neurologist 's consultation was sought , who opined to start antiepileptic medication . hence , lithium was switched to valproate ( 750 mg / day ) in december 2006 , on which he maintained completely well for 4 years , except brief re - emergence of symptoms on discontinuing valproate , which improved completely on resuming the medication . valproate was gradually tapered and stopped in january 2011 on insistence of patient and family with discussing its pros and cons . now index case has been maintaining well - off valproate for last 3 years without any episode of hypersomnolence , sexual disinhibition , sadness , or epileptic seizure . based on historical reports by kliene and levin , kls was essentially described and termed by critchley . thereafter , many researchers have reported their cases and reviewed cases with kls . here , we are reporting a case with kls , who responded well with valproate , after diagnostic dilemma and different psychotropic medications and also reviewing the other cases reported from india . in our electronic search for indian studies on kls , by using pubmed and google scholar , we could find 15 cases reported from india . of them 13 were males and 2 females , similar to male preponderance reported in the literature . while presenting to psychiatric services their age was between 9 and 26 years and they had onset between 7 and 24 years of age . in two - third of patients ( 10 out of 15 patients ) , it was preceded with fever and their episodes of somnolence were lasted from 3 days to 10 weeks . hypersomnia and hyperphagia were present in all , while two - third of patients also had social and sexual disinhibition ( 11 out of 15 patients ) . other symptoms were cognitive disturbances ( low intelligence quotient , impaired memory , confusion , and academic decline ) , irrelevant talk , and perceptual disturbances . nearly one - third of patients improved spontaneously without any medication , while rest was given lithium , carbamazepine , methylamphetamine , dextroamphetamine , and modafinil . longest asymptomatic follow - up period is reported for 2 years [ table 1 ] . reported cases with kls from india though literature supported lithium for higher response rate , but index patient had remarkable response with valproate , not with lithium , like earlier two reports . like earlier report , index patient also improved on lower dose of valproate ( divalproate 750 mg vs. 500 mg valproate ) . compared to other cases reported from india , index patient had longest follow - up ( 7 years ) and remained asymptomatic in this period , except small exacerbation on discontinuation of valproate treatment , which improved completely on resuming the drug . similar to our patient , anticonvulsants ( like valproate ) are the preferred treatment for kls patient , and may also offer benefits in case of comorbid epilepsy . valproate may be a good alternative to lithium in terms of efficacy as well as side - effect profile .

kleine - levin syndrome ( kls ) is characterized by recurrent episodes of hypersomnia and other symptoms and it is a really challenging for the physician , since its causes are not yet clear , and available treatment options are not having adequate support . here , we are reporting a case with successful use of valproate in kls and also reviewing the cases reported from india .

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a 25-year - old female presented with right eye sudden and painless blurring of vision for 4 weeks , who visited a hilly area in the himalayas , north india . no history of headache , fever , stiff neck , malaise , nausea , redness , watering of eyes , floaters , and trauma was reported . her visual acuity ( va ) in the right eye was 20/60 ( unaided ) and 20/20 in the left eye . anterior chamber was normal , relative afferent pupil defect was present , and fundus examination showed signs of papillitis , superior temporal retinitis contiguous with disc , vasculitis involving large vessels near the disc [ fig . 1 ] . examination with + 78 d revealed vitreous cells in the vicinity of neuroretinitis . fundus fluorescein angiography ( ffa ) and optical coherence tomography ( oct ) confirmed the diagnosis of neuroretinitis [ fig . the patient was empirically started on oral steroids ( prednisone 40 mg / day [ 1 mg / kg ] ) . fundus photograph showing papillitis , neuroretinitis , vasculitis ( a ) fundus fluorescein angiography showing active vasculitis . ( b ) optical coherence tomography showing vitritis rheumatoid factor , cytoplasmic antineutrophil cytoplasmic antibodies ( c - anca ) , perinuclear anti - neutrophil cytoplasmic antibodies ( p - anca ) ( anti - myeloperoxidase ) antibodies , antinuclear antibody , anti - double - standard antibody , angiotensin converting enzyme , human leukocyte antigen b-27 , rapid plasma reagin and fluorescent treponemal antibody test , treponema pallidum immobilization and t. pallidum hemagglutination assay for syphilis , toxoplasma titer , hiv elisa were within limits . lyme disease antibodies , igg and igm serum were 0.3 ( < 0.90 ) and 9.1 ( < 0.90 ) . mantoux test ( 5 mm 5 mm ) , chest x - ray , magnetic resonance imaging head , and echocardiography revealed no abnormality . on follow - up examination after 1 week , her va dropped to hand movement close to face and signs of fluid retention were present . 3b ] . considering the worsening of signs , symptoms , and positive igm tire for borrelia burgdorferi , serum western blot analysis test confirmed lyme disease . oral doxycycline 100 mg was administered twice daily for 6 weeks and prednisone was tapered over a period of 4 weeks . fundus and oct showed settling of neurosensory detachment and reduction of intraretinal fluid [ fig . ( b ) macular optical coherence tomography showing neurosensory detachment and vitritis ( a ) fundus photograph showing resolving lesions . ( b ) optical coherence tomography showing absence of neurosensory detachment and a normal foveal contour the infectious agent of lyme disease is b. burgdorferi , a spirochete , isolated successfully from blood , synovial fluid , spinal fluid , retina , and vitreous of the eye . it is transmitted by the vector ixodes tick bite and occurs in three chronological stages ; primary , secondary , and tertiary table 1 . over 50% of untreated , treated initially , and on treatment , patients may develop stage 3 lyme disease . hence , long follow - up is recommended for early diagnosis of cardiac , neurological , and arthritic involvement . the centers for disease control and prevention made lyme disease a reportable disease in 1982 . major manifestations individual case reports with positive lyme serology have reported papillitis , anterior ischemic optic neuropathy , optic neuritis , and neuroretinitis ; false positives have been up to 10% among residents of endemic areas without any apparent signs of infection . the current definition of lyme disease includes a patient who develops erythema migrans ( em ) within 30 days of exposure in an endemic area or endemic area exposure , without em , but with signs involving one organ system and a positive laboratory test or no history of exposure , but with em as well as involvement of two organ systems or no exposure in an endemic area , but with em and a positive serology . our patient was diagnosed as lyme disease based on history of exposure , involvement of one organ , i.e. , eye and positive serology for b. burgdorferi . neuroretinitis is a focal inflammation of the optic nerve and peripapillary retina or macula of either infectious or idiopathic etiology . infectious causes are cat scratch disease , syphilis , lyme disease , toxoplasmosis , mumps , salmonellosis , tuberculosis , and histoplasmosis . although rare in india , we need to consider lyme disease in the differential diagnosis of neuroretinitis , especially if the patient hails from a forested area . babu and murthy and vanya et al . have reported resolution of neuroretinitis with a combination of doxycycline and corticosteroids . long - term use of antibiotics is successful in preventing disease progression to tertiary stage . we conclude that neuroretinitis can be the presenting and the only presentation of lyme disease , hence should be considered in the differential diagnosis of neuroretinitis . documentation with fundus photography , ffa , and oct for response to treatment is recommended . doxycycline and corticosteroids should be started at the earliest as it is a treatable disease .

we present a case of neuroretinitis as presenting and the only presentation of lyme disease in a 25-year - old female who visited hilly areas in the himalayas of north india . she presented with right eye sudden and painless blurring of vision . her vision at presentation was 20/60 . she had fundus examination ; fundus fluorescein angiography ( ffa ) and optical coherence tomography ( oct ) imaging showed classical features of neuroretinitis . no other organ was involved . oral steroids were prescribed and relevant investigations sent for noninfective and infective causes . worsened visual acuity ( va ) to hand movement and positive igm titers for borrelia burgdorferi led to the diagnosis of lyme disease - associated neuroretinitis . treatment with oral doxycycline plus oral steroids for 4 weeks revealed va of 20/20 and resolution of fundus and oct changes . neuroretinitis as presenting and the only presentation of lyme disease will be discussed with serial fundus , ffa , and oct pictures .

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generation of transgenic lines is described in the supplementary methods . to induce recombination and subsequently genetically label cardiomyocytes , embryos / adults were treated with 4-oht followed by a wash period of at least 1 week prior to amputation . adult fish were anesthetized in 0.4%tricaine and secured ventral side up in a slotted sponge . watchmaker forceps were used to remove the surface scales and penetrate the skin , muscle , and pericardial sac . once exposed , the ventricle was gently pulled at the apex and cut with iridectomy scissors . after surgery , fish were immediately returned to system water . at the specified time points , hearts were removed and fixed in 4% paraformaldehyde overnight at 4c , washed several times in pbs , equilibrated in 30% sucrose in pbs , and frozen for cryosectioning . fish were anesthetized in 0.4%tricaine , and 0.5ml of a 2.5mg / ml solution of brdu ( in pbs ) was injected into the abdominal cavity once every 24 h for 7 d. after 14 d , hearts were removed and fixed in 4% paraformaldehyde overnight at 4c , washed several times in pbs , equilibrated in 30% sucrose in pbs , and frozen for cryosectioning . cyclapolin 9 ( sigma c6493 ) was dissolved in dmso and added to 400ml system water to a final concentration of 3m . generation of transgenic lines is described in the supplementary methods . to induce recombination and subsequently genetically label cardiomyocytes , embryos / adults were treated with 4-oht followed by a wash period of at least 1 week prior to amputation . adult fish were anesthetized in 0.4%tricaine and secured ventral side up in a slotted sponge . watchmaker forceps were used to remove the surface scales and penetrate the skin , muscle , and pericardial sac . once exposed , the ventricle was gently pulled at the apex and cut with iridectomy scissors . after surgery , fish were immediately returned to system water . at the specified time points , hearts were removed and fixed in 4% paraformaldehyde overnight at 4c , washed several times in pbs , equilibrated in 30% sucrose in pbs , and frozen for cryosectioning . fish were anesthetized in 0.4%tricaine , and 0.5ml of a 2.5mg / ml solution of brdu ( in pbs ) was injected into the abdominal cavity once every 24 h for 7 d. after 14 d , hearts were removed and fixed in 4% paraformaldehyde overnight at 4c , washed several times in pbs , equilibrated in 30% sucrose in pbs , and frozen for cryosectioning . cyclapolin 9 ( sigma c6493 ) was dissolved in dmso and added to 400ml system water to a final concentration of 3m .

although mammalian hearts show virtually no ability to regenerate , there is a growing initiative to determine whether existing cardiomyocytes or progenitor cells can be coaxed into eliciting a regenerative response . in contrast to mammals , a number of non - mammalian vertebrate species are able to regenerate their hearts13 , including the zebrafish4,5 , which can fully regenerate its heart following amputation of up to 20% of the ventricle . to directly address the source of newly formed cardiomyocytes during zebrafish heart regeneration , we first established a genetic strategy to lineage - trace cardiomyocytes in the adult fish , based on the cre / lox system widely used in the mouse6 . using this system , we show here that regenerated heart muscle cells are derived from the proliferation of differentiated cardiomyocytes . furthermore , we show that proliferating cardiomyocytes undergo limited dedifferentiation characterized by the disassembly of their sarcomeric structure , detachment from one another and expression of regulators of cell cycle progression . specifically , we show that polo - like kinase1 ( plk1 ) is an essential component of cardiomyocyte proliferation during heart regeneration . our data provides the first direct evidence for the source of proliferating cardiomyocytes during zebrafish heart regeneration and indicates that stem / progenitor cells are not significantly involved in this process .

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a 32-year - old man was transferred to an intensive care unit ( icu ) due to respiration difficulties from a hepatology ward where he had been admitted after a 7-day history of symptoms of acute viral hepatitis a ( ha ) and a 3-day history of progressive distal and proximal weakness of limbs with additional facial weakness . initial laboratory tests performed at the ward ( results listed in table 1 ) suggested acute viral ha infection with high igm anti - ha antibody titers . despite improvement in liver function and hepatitis symptoms , nerve conduction was studied and cerebrospinal fluid ( csf ) was tapped due to progressive weakness . a diagnosis of guillain - barr syndrome ( gbs ) was supported by albuminocytologic dissociation ( 1 white blood cell / mm , 2 red blood cells / mm , 115.0 mg / dl protein , and 58 mg / dl glucose ) and multiple motornerve - conduction defects with decreased compound motor action potentials ( table 2 ) . on the second day in the icu his heart rate was 85~120 beats / min and his arterial blood pressure was up to 200/110 mmhg . his pupils were dilated to 5 mm and not reactive to light . on day 4 a positive pupil response to a 0.1%-pilocarpine test indicated ciliary postganglionic parasympathetic neuropathy with supersensitivity to acetylcholine . these tests and signs indicated the absence of all brain reflexes , suggesting the presence of peripheral deafferentation . in addition , complementary laboratory tests for vasculitis or other infectious agents were normal except for the presence of latent herpes simplex virus ( hsv ) infection . a polymerase chain reaction for hsv was negative , and no symptoms of hsv infection were detected . a follow - up nerve - conduction study performed 2 weeks after transfer to the icu suggested severe demyelinating sensorimotor polyneuropathy ( table 2 ) . intravenous gammaglobulin ( ivig ) ( 0.4 g / kg / day ) was administered for 5 days , but his neurological status had worsened due to fulminant deafferentation . therefore , pulse therapy with methylprednisolone ( 500 mg / day ) were given for 3 days . after the initial 5-day course of therapy , ivig was added twice weekly 2 weeks later . three months later he recovered complete power in his upper and lower limbs , except for a residual deficit of left foot weakness ( dorsiflexor : grade 4 , plantar flexor : grade 4 ) and bilateral hypopathic sensory change of soles . the development of clinical symptoms of hepatitis , marked increases in bilirubin , aspartate aminotrasferase , alanine aminotrasferase ( alt ) , and -glutamyltransferase levels , and a positive igm - ha virus antibody test supported the diagnosis of acute ha . cases exhibiting an association between gbs and ha are extremely rare.1 the reported clinical features of nine reviewed cases of gbs following ha were as follows : ( 1 ) a uniformly good outcome of the neuropathic symptoms , independent of the level of alt , which corresponds to the severity of liver dysfunction ; ( 2 ) highest occurrence in men ; and ( 3 ) the interval between the onset of the hepatitis and the development of neuropathic symptoms is less than 14 days.2 the hsv infection in our patient , in spite of neither symptoms nor signs , might have aggravated the severity of gbs . the initial nerve - conduction study and blink - reflex test in this patient revealed inexcitability of most nerves , which was due to distal pathology of the motor axons : either a distal conduction block or axonal degeneration . the nature of this pathology can not be predicted by the results of an initial electrophysiological evaluation.3 the very prolonged distal motor latencies in the electromyogram recorded in a subsequent nerve - conduction study suggested the presence of severe demyelinating polyneuropathy and axonopathy . in the case of gbs mimicking cerebral death,4 a sural nerve biopsy indicated that demyelination was the early pathological mechanism . therefore , the exact physiopathology and whether our patient had distal demyelination and conduction block with secondary axonal loss or axonal degeneration , or both , remained unclear . the various treatments used for fulminant gbs mimicking cerebral death are plasma exchange , ivig , or plasma exchange and corticosteroids.4 our patient was treated with ivig to modulate the immunologic reaction , and with high - dose pulse therapy with methylprednisolone for suppressing the acute severe inflammation in the peripheral nervous system . there is no evidence that conventional doses of corticosteroids ( around 60 mg of prednisone daily ) are effective in shortening the course of or reducing residual deficits in acute gbs.5 however , high - dose steroids are perhaps currently best applied to patients who can not tolerate plasma exchange ( e.g. , due to severe cardiovascular dysautonomia ) or when other treatments are unavailable.6 - 8 our patient recovered progressively , and could walk alone with mild weakness of the left foot at 3 months after admission . gbs mimicking brain death usually has a poor recovery rate and a high mortality , particularly in relation to dysautonomia.9 the timely application of combination pulse therapy with both ivig and methylprednisolone might improve the prognosis of fulminant gbs . in summary , in rare cases gbs presents with signs of coma and absent brainstem reflexes .

a 32-year - old man was transferred to an intensive care unit due to respiratory difficulties with a 4-day history of progressive areflexic quadriparesis following acute hepatitis a. a nerve - conduction study revealed inexcitability of most nerves . the cerebrospinal fluid showed albuminocytologic dissociation , suggesting guillain - barr syndrome ( gbs ) . the patient appeared brain dead on day 4 , showing absent brainstem reflexes , respiratory failure , and fully dilated and fixed pupils . this case is an example of how gbs can evolve and simulate a brain - dead state from fulminant deafferentation following acute hepatitis a.

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thrombotic thrombocytopenic purpura ( ttp ) is a rare disorder with an incidence of 45 cases per million per year . timely diagnosis and availability of effective treatment such as plasma exchange therapy have reduced the morbidity and mortality significantly . usually , it is idiopathic or autoimmune , but several predisposing factors have been described to cause secondary ttp . in this case report , we discussed a very rare presentation of ttp secondary to dengue virus infection and how the timely diagnosis along with the immediate institution of appropriate management helped us to cure the patient . a 35-year - old female with no other comorbidities was admitted to the hospital with complaints of fever and vomiting over 1 week . her investigations revealed a low platelet count and dengue igg , and igm antibodies were positive . she was symptomatically treated at a local hospital and was transfused 16 units of random donor platelets over a period of 6 days . but despite this , platelet count was remaining low . the patient was drowsy , arousable to verbal commands only , and had decreased limb movement on the right side . laboratory investigations were showing anemia , thrombocytopenia , and increased lactate dehydrogenase ( ldh ) level as shown in table 1 . her peripheral blood smear revealed numerous schistocytes and computed tomography ( ct ) brain was unremarkable . ultrasonography abdomen was suggestive of bulky kidneys , and she was retrovirus negative . with this clinical picture and laboratory findings , she was diagnosed as a case of ttp and was advised urgent plasma exchange therapy . although there is no firm recommendation for administration of steroids in ttp , we started her on low - dose injection methylprednisolone ( 100 mg daily ) considering its autoimmune etiology . on the 2 day of the admission , she had an episode of convulsion which was treated with anticonvulsive medication . she required intubation and ventilatory support because of postconvulsion low glasgow coma scale ( gcs ) . she convulsed again on 3 day with drop in hemoglobin and platelets [ table 1 ] , so injection rituximab 500 mg was added to treatment in addition to plasma exchange . platelet count improved , serum ldh level showed decline over a period [ table 1 ] . she underwent total eight plasmapheresis cycles , and before discharge , her platelet counts were 152 mm , serum ldh was 511 we followed her up in the outpatient department , and at 6 months , she is well with normal hemogram . this patient had dengue viral infection confirmed by serology which was complicated by ttp during the acute phase of dengue viral infection . we diagnosed this by clinical features and ruling out other differential diagnosis by laboratorial and radiological tests . the patient responded well to the plasma exchange therapy with complete recovery from symptoms and no recurrence after 6 months follow - up . usually , it presents as mild / asymptomatic type of infection ; however , at times , it may manifest in more severe forms such as dengue hemorrhagic fever , or dengue shock syndrome . many unusual complications have been observed with dengue viral infection such as hepatic damage , cardiomyopathy , and encephalopathy . the presence of ttp with dengue viral infection is very rare presentation and has been reported in very few case reports . ttp itself is a rare clinical syndrome characterized by fever , microangiopathic hemolytic anemia , thrombocytopenia , central nervous system involvement , and renal impairment . secondary ttp can occur after infections , medications ( e.g. , clopidogrel , cyclosporine ) , autoimmune diseases , malignancies , pregnancy , and bone marrow transplantation . infections known to cause thrombotic microangiopathy include hepatitis c , parvovirus b19 virus infection , hiv infection as well as patient with dental foci or streptococci infection . pathophysiology of ttp includes deficiency of protease enzyme ( adamts13 ) that cleaves von willebrand factor ( vwf ) in small segments . in the absence of adamts13 enzyme , large vwf cause platelet aggregation and fibrin deposition in small vessels and the patient was diagnosed as having dengue viral infection by the presence of igm and igg antibodies and treated accordingly with fluid resuscitation and platelet transfusion . but later , the patient showed features such as fever , thrombocytopenia , hemolytic anemia , and neurological involvement in the form of decreased consciousness , hemiparesis , and seizures ( ct brain - normal ) . all these features were suggestive of ttp and patient responded well to plasma exchange therapy , steroid therapy , and injection rituximab . although the exact incidence of ttp in dengue viral infection is not known , such cases are reported in the recent past . hence , special attention must be given to dengue virus infection patients presenting with signs and symptoms of ttp in the future . the prompt clinical recognition of such complication and early initiation of specific therapy with plasma exchange is likely to improve the patient 's outcome .

here , we present an unusual occurrence of thrombotic thrombocytopenic purpura ( ttp ) in a case of dengue fever . both the conditions are fatal and can result in significant mortality and morbidity if left untreated . in this case , as soon as , we diagnosed the patient as having ttp , we treated her with plasma exchange therapy , steroids , and monoclonal antibodies such as rituximab . the patient responded very well to the treatment and completely recovered from neurological symptoms and laboratory parameters also normalized . hence , timely diagnosis and starting appropriate treatment immediately are key factors for successful outcome .

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before ecd can be used for analysis , they must first be prepared so that they accurately represent the health risks and outcomes of the patients studied , as well as the care provided by health care system . davis and colleagues report on a retrospective observational study in veterans with rheumatoid arthritis to validate diagnostic and procedural codes for identification of acute cardiovascular events . beyond the specific population and set of outcomes in this example , reimer and madigan demonstrate how the development of a fully integrated medical transport record for patients undergoing medical transport as an example will offer the ability to address complex questions related to patients clinical outcomes in a real - world clinical setting while providing an electronic data infrastructure that can enable high - quality , clinically rich , prospective , and multisite data collection to support cer . stuart and colleagues outline the challenges in estimating causal effects using electronic health data generally , and offer some solutions , with particular attention to propensity score methods . the methods are illustrated with a case study showing how medicare and medicaid administrative data can be used to estimate the effect of the medicare part d prescription drug program among individuals with serious mental illness . zurovac and colleagues demonstrate how the concept of multifactorial experiments , drawn from the evaluation literature , offers promise for cer with ehrs . they examine some of the unique aspects of such missing data , present some statistical advice about how to handle these issues , and provide some suggested areas for future methodological research . a more specific challenge in using ecd is that observations are not scheduled as they would be in a designed randomized clinical trial , but rather occur at irregular intervals coincident with patient visits , which potentially depend on outcomes . luo and colleagues show how discrete - time hidden markov models can be used to estimate transition rates in this context , using chronic kidney disease as an example . a final paper in this issue provides an example of how methods for preparing and analyzing ecd can come together to enable rigorous cer . written in the form of a protocol for a prospective , longitudinal cohort study , sills and colleagues demonstrate how survey methodologies and secondary analysis of existing structured clinical , administrative , and claims data can be used to estimate the effects of patient - centered medical home characteristics on asthma control in adults and children . the setting for this research is the scalable architecture for federated translational inquiries network ( saftinet ) , an ahrq - funded safety net - oriented practice - based research network , which is designed to measure these variations in delivery system characteristics . as useful as they are , these papers only begin to address the methodological developments needed to advance the national dialogue on the use of ecd to conduct cer , support qi , and generally to improve outcomes in a learning health care system . these papers offer a beginning snapshot of some critical ideas and innovations shaping the field . egems remains interested in publishing researcher perspectives on methodological challenges resulting from using ecd and lessons learned from facing these challenges , and welcomes future methods - related submissions to our general issue . for more information on submitting papers i encourage you to read the papers in this collection and think about whether your organization has developed similar approaches or radical alternatives and write about them . you might also try some of the approaches discussed here , and let us know how they work out . we are particularly interested in papers that address key topics raised in prior edm forum discussions , including strategies for evaluating and addressing missing data and other data quality issues ; analytic strategies that can account for granular temporal or spatial information ; and new , rigorous methodological approaches to maximizing the use of big data to generate new evidence and determine what works best for whom and under what conditions .

whether one reads computerworld or institute of medicine issue briefs , it s clear that most now accept the idea that existing electronic clinical data ( ecd ) and other health records can be used to manage and improve the processes , outcomes , and the quality of health care . indeed the increasing popularity of the term learning healthcare system signals the broad acceptance of the idea that routinely collected clinical data can indeed should be used to advance knowledge and support continuous learning . but despite what the big data enthusiasts say , none of this is easy without the appropriate analytical methods.this commentary introduces the seven papers in egems second special issue , which are the result of invitations to researchers who have participated in edm forum activities as well as an open call for paper in early summer 2013 . these papers offer a beginning snapshot of the ways innovative thinkers across the country are developing methodology to advance the national dialogue on the use of ecd to conduct cer , support qi , and generally to improve outcomes in a learning healthcare system .

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a 15-year old boy attempted suicide by taking a high dose of disulfiram ( 20 mg ) . upon arrival at the hospital , he was alert and vital signs were stable . one month after , he suddenly developed an acute insult consisted of anxiety attack and subsequent retrocollis and forceful upward deviation of the eyes . during the attack , he could not close his eyes and speak , making only grunting noises . he could not move his eyes voluntarily at all , but horizontal oculocephalic reflexes could be elicited . the frequency , duration and intensity of the attacks increased gradually over a period of eight years , occurring more than 10 times a day and lasted up to 2 hours . he had no motor weakness or sensory deficits , but he needed a help to walk due to foot dystonia . t2-weighted brain mri studies showed high signal intensity lesions at the bilateral globus pallidus and left substantia nigra ( figure 1 ) . levodopa treatment was not effective , but the frequency of the attacks decreased markedly after trihexyphenidyl hydrochloride ( 2.5 mg tid ) treatment . also , the foot dystonia improved partially and the patient could walk a short distance without assistance . disulfiram is metabolized to cyanide disulfide ( cs2 ) and produce lesions at the globus pallidus and substantia nigra pars reticulata in monkeys.7 in huans , pallidal or lenticular lesions after disulfiram intoxication have been reported.6,7 however , to our knowledge , lesion at the substantia nigra after disulfiram intoxication is rarely documented on brain mri studies . ogc occurs frequently in association with neuroleptic treatment , postencephalitic parkinsonism , and focal brain lesions at the putamen or globus pallidus.1,2,4,5 these findings suggest that ogc can be caused by basal ganglia dysfunction , particularly of the dopaminergic system . in our patient , neuronal discharges from pathologically reorganized basal ganglia circuit to the midbrain ocular motor center might lead to tonic deviation of the eyes . we reported a patient who developed disulfiram induced parkinsonism , dystonia , and ogc , responding markedly to the anticholinergics treatment .

we report a man who developed oculogyric crisis one month after disulfiram intoxication . brain mri showed lesions involving bilateral globus pallidus and left substantia nigra . in our patient , neuronal discharges from pathologically reorganized basal ganglia circuit to the mid - brain ocular motor center might lead to tonic deviation of the eyes .

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initiatives such as the surviving sepsis campaign , launched in 2002 as a collaborative initiative of the european society of intensive care medicine , the international sepsis forum , and the society of critical care medicine , aim to effectively reduce risk of death from severe sepsis and septic shock . nonetheless , although substantial benefits raised from the implementation of this campaign have been obtained , much work remains if we are to realise the full potential promised by this strategy . recently , new treatment approaches based on interventions for coagulation or inflammation have failed to improve survival in sepsis . a deeper understanding of the processes leading to sepsis is necessary before we can design an effective suite of interventions . dysregulation of the immune response to infection is acknowledged to contribute to the pathogenesis of the disease . critical illness itself , surgery and concomitant comorbidities such as diabetes , chronic renal failure or chronic obstructive pulmonary disease affect host responses to infection , which could in turn facilitate the development of sepsis or impair outcome once sepsis is established . despite these precedents , the potential role of immunological monitoring in this disease has not been appropriately considered to the present moment . for years , two phases have been described in sepsis : an initial systemic inflammatory response syndrome followed by the negative feedback of a secondary compensatory anti - inflammatory response syndrome . in contrast to this long - held view , marchant and colleagues and our group have observed that production of the immunosuppressive cytokine il-10 occurs from the very first hours following the diagnosis of severe sepsis or septic shock , and that it is directly associated with the secretion of proinflammatory cytokines [ 7 - 9 ] . levels of igg , igm and iga at diagnosis have been reported to correlate directly with survival . in turn , nonsurvivors have lower levels of c4 ( a protein of the complement system ) than survivors . natural killer cell counts and function also seem to have an important role in this disease . severe depletion of immune effector cells is a universal finding in all age groups during sepsis . quantification of lymphocyte subsets and evaluation of their function could thus have diagnostic and prognostic value in sepsis . at the genomic level , repression of networks corresponding to major histocompatibility complex antigen presentation cumulative evidence supports the notion that the immunological situation of the patient is linked to the final outcome in sepsis . immunological monitoring could thus contribute to the prevention or the treatment of sepsis in a personalised and timely manner . interestingly , there is no currently available information on the potential role of proper immunological monitoring for the prevention of sepsis . immunological monitoring could help to identify patients with immunological deficiencies ( secondary to their disease process , treatment , and so forth ) at higher risk for developing community acquired or nosocomial sepsis . periodic monitoring of patients hospitalised in key services ( that is , oncology , transplantation units , critical care units ) could help to identify specific humoral or cellular immunity defects that could be addressed by implementation of prophylactic measures , such as administration of intravenous immunoglobulin ( ivig ) or proper cover with broad - spectrum antibiotics . prompt implementation of an accurate treatment is key to the final outcome in patients with sepsis . immunological monitoring could help to improve outcome in sepsis , by providing early detection of individuals at higher risk for developing complicated outcomes as well as relevant information for guiding treatment . for example , the treatment effect of ivig on mortality for patients with septic shock is currently controversial . measuring endogenous levels of immunoglobulins could improve the render of ivig in sepsis , helping the clinician to better select those patients to be treated ( those exhibiting marked hypogammaglobulinemia ) . once more , there is a dramatic absence of information on the potential role of prior endogenous immunoglobulin quantification in the clinical assays evaluating ivig for the treatment of this disease . immunological monitoring could help also to guide therapies with immunomodulatory drugs with an anti - inflammatory effect or , alternatively , with an immunostimulatory effect . although not currently practiced , monitoring of the patient 's immunological situation is feasible ( at least from a quantitative point of view ) in most hospitals . quantification of immunoglobulins , complement proteins and t cells ( cd4 , cd8 ) in peripheral blood is an easily available routine test . other tests of potential interest for immunological monitoring in sepsis include the quantification of hla - dr in the surface of blood monocytes or the evaluation of percentages of circulating cd4cd25t - regulatory cells in blood . lastly , the use of genomic signatures ( gene expression , mirna , dna methylation profiles ) offers new opportunities to assess the immunological status of the patient . although diffuse and limited , current available information supports the development of large comprehensive studies aimed to urgently evaluate immunological monitoring as a tool to prevent or treat sepsis , and thereby to diminish the morbidity and mortality associated with this severe condition . hla : human leukocyte antigen ; ivig : intravenous immunoglobulin ; il : interleukin ; mirna : microrna . ra , jw and jfb - m provided the immunological insight and participated in writing the article . et , da - o , im - l and pr provided the clinical insight and participated in writing the article . the authors want to thank dr david livermore ( norwich medical school , university of east anglia ) for his constructive comments on this letter .

the clinical , human and economic burden associated with sepsis is huge . initiatives such as the surviving sepsis campaign aim to effectively reduce risk of death from severe sepsis and septic shock . nonetheless , although substantial benefits raised from the implementation of this campaign have been obtained , much work remains if we are to realise the full potential promised by this strategy . a deeper understanding of the processes leading to sepsis is necessary before we can design an effective suite of interventions . dysregulation of the immune response to infection is acknowledged to contribute to the pathogenesis of the disease . production of both proinflammatory and immunosuppressive cytokines is observed from the very first hours following diagnosis . in addition , hypogammaglobulinemia is often present in patients with septic shock . moreover , levels of igg , igm and iga at diagnosis correlate directly with survival . in turn , nonsurvivors have lower levels of c4 ( a protein of the complement system ) than the survivors . natural killer cell counts and function also seem to have an important role in this disease . hla - dr in the surface of monocytes and counts of cd4+cd25 + t - regulatory cells in blood could also be useful biomarkers for sepsis . at the genomic level , repression of networks corresponding to major histocompatibility complex antigen presentation is observed in septic shock . in consequence , cumulative evidence supports the potential role of immunological monitoring to guide measures to prevent or treat sepsis in a personalised and timely manner ( early antibiotic administration , immunoglobulin replacement , immunomodulation ) . in conclusion , although diffuse and limited , current available information supports the development of large comprehensive studies aimed to urgently evaluate immunological monitoring as a tool to prevent sepsis , guide its treatment and , as a consequence , diminish the morbidity and mortality associated with this severe condition .

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patients with graves orbitopathy have a higher probability of myasthenia gravis than the normal population.1 according to a large retrospective case series , myasthenia gravis was diagnosed in two of 150 patients with graves orbitopathy ( 1.3%).2 patients with graves orbitopathy commonly show eyelid retraction and/or hypotropia and/or esotropia , as well as exophthalmos , lagophthalmos , exposure keratopathy , and less frequently , compressive optic neuropathy.3 however , patients with myasthenia gravis often demonstrate ptosis and/or exotropia , but a consistent pattern of eye movement disturbances is usually not present.3 upper eyelid retraction in graves orbitopathy and myasthenia gravis ( go - mg ) is frequently camouflaged , and these patients may show a normal upper eyelid height . we herein report a patient with go - mg with left normal eyelid height , but in whom the upper eyelid retraction was disclosed after edrophonium chloride administration . a 46-year - old man with graves disease , well controlled by thiamazole 5 mg / day , was referred to our clinic to treat his graves orbitopathy . although both eyes had exophthalmos ( 20 mm od , 19 mm os ; normal range , < 17 mm)4 , he demonstrated a normal left eyelid height and right ptosis , ie , margin reflex distance-1 , 3.5 mm os and 0.5 mm od , respectively ( figure 1 ) . his primary eye position was exotropic , dominantly on his right side , and the upward gaze of the right eye was severely restricted ( figure 2 ) . coronal computed tomography of the orbits showed bilateral enlargement of the inferior rectus muscle , medial rectus muscle , superior oblique muscle , and superior rectus muscle - levator muscle complex ( figure 3a ) . axial computed tomography demonstrated bilateral medial and lateral recti muscle enlargement ( figure 3b ) . localization of these muscle involvements did not match the characteristics of the eye movement disorder ( figure 3c ) . because the aforementioned findings raised suspicion for the presence of both graves orbitopathy and myasthenia gravis , we performed an edrophonium chloride test.5 the margin reflex distance-1 had improved to 2.5 mm od and 8.0 mm os ( figure 4 ) , although the eye movement had not clearly improved . some days later , the result of a serum acetylcholine receptor antibody assay was positive ( 1.8 nmol / l ; normal , < 0.2 nmol / l ) . because the patient could completely close his left eye , we prescribed pyridostigmine bromide 180 mg / day,5 and the eyelid height stabilized the association between graves orbitopathy and myasthenia gravis has long been recognized.2,6 although it is not difficult to differentiate clinically between simple graves orbitopathy and myasthenia gravis , overlapping clinical features , such as upper eyelid height and/or eye movement disturbances occasionally cause diagnostic confusion , especially in patients with normal thyroid function . the most frequent sign of graves orbitopathy is upper eyelid retraction,7 which is caused by overaction of the mller s muscle because of excess catecholamines and cicatricial contraction of the levator muscles after the inflammatory process.7 for the overaction , topical guanethidine therapy is sometimes effective.8 for the contraction , steroid administration and botulinum toxin injection are indicated during the active phase , and surgical correction is necessary in the static phase.7 graves orbitopathy also shows eye movement disturbances , which have a restrictive myopathy pattern.3 the inferior and medial rectus muscles are frequently involved , and imaging discloses their hypertrophy when in the active phase . on the other hand , ptosis and diplopia are present in about 90% of patients with myasthenia gravis , and these ocular symptoms are an initial complaint in 20% of patients with myasthenia gravis.911 muscle hypertrophy does not exist on imaging in myasthenia gravis.12 no particular predilection of extraocular muscle involvement is shown in myasthenia gravis . however , solitary paresis usually occurs , in the form of an adduction deficit resulting in exotropia , which was the case in the present patient . exotropia is more common in ocular myasthenia gravis.3 in spite of the obvious differences between graves orbitopathy and myasthenia gravis , each condition shares several features , potentially making it difficult to reach a correct diagnosis . upper eyelid ptosis , typically suggestive of myasthenia gravis , may be seen with graves orbitopathy as a result of levator myopathy,13 apical compression,14,15 and pseudoptosis secondary to upper eyelid retraction in the fellow eye.16 however , if ptosis develops in a patient with graves orbitopathy , simultaneous myasthenia gravis should be considered,17 although ocular myasthenia gravis with orbital pain may imply orbital inflammation.18 in our patient , the right ptosis and exotropia suggested concomitant myasthenia gravis , which motivated us to perform an edrophonium chloride test . the left upper eyelid , appearing to have a normal height , was retracted to margin reflex distance-1 8.0 mm , and the right side , regarded as ptosis , moved to margin reflex distance-1 2.5 mm ( figure 4 ) . this examination demonstrated that the left upper eyelid originally had an upper eyelid retraction that was camouflaged by the ocular myasthenia gravis . treatment of our patient was complicated because of laterality and strabismus induced by myasthenia gravis . when the eyelid height stabilizes after medication with improvement of strabismus , a sling surgery may be performed on the right upper eyelid . however , if strabismus persists , this strategy must be abandoned . when left upper eyelid retraction is conspicuous with lagophthalmos , left upper eyelid lengthening surgery may be performed.19 in conclusion , upper eyelid retraction in patients with go - mg may be camouflaged by a myasthenia effect . the upper eyelid height must be carefully monitored in patients with graves orbitopathy to detect the presence of concomitant myasthenia gravis .

patients with graves orbitopathy have a higher probability of myasthenia gravis than does the normal population . overlapping clinical features cause diagnostic confusion in such a situation . we herein report a patient with graves orbitopathy and myasthenia gravis ( go - mg ) with normal left eyelid height , but in whom upper eyelid retraction was shown after edrophonium chloride administration . upper eyelid retraction in go - mg is occasionally masked by a myasthenia effect . the upper eyelid height must be carefully monitored in patients with graves orbitopathy to detect the presence of concomitant myasthenia gravis .

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microcystic adnexal carcinoma ( mac ) is a rare malignant cutaneous neoplasm with pilar and eccrine gland differentiation . mac was first described as a separate clinical entity by goldstein et al in 1982 . it is locally aggressive but rarely metastasizes , usually presenting as a slow growing asymptomatic lesion on the head and neck . fewer than 300 cases have been reported worldwide , according to an analysis by yu et al . a 67-year - old man presented to a primary care skin cancer clinic in melbourne , australia for a routine six - month skin cancer examination . there was a long history of recreational sun exposure . seven separate basal cell carcinomas had required excision from his forehead , nose , pinna , posterior neck , mid back calf in the last decade . most recently a moderately differentiated squamous cell carcinoma had been excised from his right upper forehead some six months previous . a whole body skin examination was undertaken with the aid of a heine delta 20 non - polarizing dermatoscope ( heine optotechnik , herrshing , germany ) . digital clinical and dermatoscopic images were taken with a medicam 800 fotofinder non - polarizing camera ( fotofinder systems gmbh , aichner , birnbach , germany ) , the dermatoscopy images being at 20 magnification . examination confirmed fitzpatrick skin type 2 with severe actinic damage to the skin of his face , upper trunk and distal limbs with multiple solar lentigines and actinic keratoses . significant actinic damage to the lower lip ( actinic cheilitis ) was apparent . during the examination the patient pointed out a white , scar - like lesion on his mid left cheek measuring 8 4 mm in diameter . it was non - pigmented and was composed of a clearly demarcated flat white plaque ( figure 1 ) . dermatoscopically the lesion exhibited a dense white structureless area with fine linear branched blood vessels centrally . a notable feature was the white clods of variable diameter superiorly ( figure 2 ) . eccrine syringoid carcinoma , a rare malignant cutaneous adnexal tumor , should also be included in the differential diagnosis . an excisional biopsy was performed using an elliptical excision , and the specimen was submitted for assessment by a specialist dermatopathologist . examination of the histological sections revealed a deeply invasive dermal neoplasm composed superficially of keratin filled cysts with calcification , and in the underlying reticular dermis , of infiltrative aggregates of basaloid cells in slender strands and syringomatoid aggregates . the differential diagnosis was between a microcystic adnexal carcinoma and a fibrosing basal cell carcinoma with follicular differentiation . this staining pattern , although not entirely specific , was more in favour of microcystic adnexal carcinoma than fibrosing basal cell carcinoma . ber - ep4 expression has been noted in 38% of microcystic adnexal carcinomas and 100% of basal cell carcinomas . however ck15 is expressed in 92% of microcystic adnexal carcinomas , whereas basal cell carcinomas are negative . hence , in conjunction with the positive cea , the findings favoured a microcystic adnexal carcinoma ( figures 3 to 11 ) . a search of the literature has not discovered any previously published dermatoscopy images of a microcystic adenexal carcinoma . the two most notable dermatoscopic features of the lesion we present were the dense white structureless area centrally and the white clods of variable diameter peripherally . white clods of this pattern have also been observed in the more common adnexal skin tumor trichoepithelioma and may represent keratin retention cysts . microcystic adenexal carcinoma is currently considered a rare tumor . however , such rarities will present more often as the world population increases in age and has increased access to modern medicine . the authors feel it is important to publish such dermatoscopic images as ours to as wide an audience as possible to aid clinical diagnosis in future .

we present a case report of a microcystic adnexal carcinoma on the cheek of a 67-year - old man . clinical , dermatoscopic and dermatopathologic images are presented . a search of the literature has not discovered any previously published dermatoscopy images of microcystic adenexal carcinoma .

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the causes are multifactorial , with extramedullary pulmonary hematopoiesis being described as a rare etiological factor ( 2 ) . this occurs in conditions such as myeloproliferative disorders , hemoglobinopathies and marrow infiltrating diseases . in chronic myeloproliferative disorders , extramedullary hematopoiesis in the lungs may be suspected on computed tomography ( ct ) chest scans in the presence of diffuse ground - glass opacities or interstitial thickening ( 3 ) . we report the case of a 66-year - old man in whom chest ct scan did not reveal any lung parenchymal abnormality . a pulmonary extramedullary hematopoiesis causing pulmonary hypertension and severe tricuspid regurgitation was diagnosed on technetium-99 m ( tc-99 m ) sulfur colloid bone marrow scan and single - photon emission computed tomography ( spect)/ct . a 66-year - old man with a known primary myelofibrosis ( diagnosed in december 2008 at an outside institution ) presented to our hospital with complaints of shortness of breath and abdominal bloating in march 2012 . he had multiple hospital admissions for the worsening of its dyspnea over the previous two years . on clinical examination , he was dyspneic with an elevated jugular venous pressure and bipedal pitting edema . the total white cell count was markedly raised ( 41.2 10/l ) with a low hemoglobin level ( 5.3 g / dl ) . a ct pulmonary angiogram did not show any pulmonary embolism ; however , the right atrium and the main pulmonary arteries were dilated , suggesting a pulmonary hypertension with reflux of contrast into the inferior vena cava and hepatic veins ( fig . 1e ) . the two - dimensional echocardiography confirmed a severe tricuspid regurgitation with marked right atrial dilatation and moderately impaired right - ventricular systolic function . a tc-99 m sulfur colloid bone marrow scan with spect / ct imaging was performed ( symbia , siemens medical solutions , erlangen , germany ) with a background history of primary myelofibrosis to exclude pulmonary hematopoiesis as the cause of pulmonary hypertension . the planar gamma imaging showed a hepatosplenomegaly with increased tracer accumulation in the spleen , compatible with an increased hematopoietic activity resulting from an underlying myelofibrosis ( fig . a moderate degree of tracer activity in a diffuse pattern was noted in both thoracic regions ( fig . the spect / ct imaging confirmed the location of an increased thoracic tracer activity in the lungs ( fig . a lung biopsy was not carried out in view of the increased risk of pulmonary hemorrhage in the presence of pulmonary hypertension . a hydroxyurea treatment was started for the patient to control the markedly raised total leukocyte count and massive splenomegaly . concurrently , he was referred to a short course radiation - therapy to the lungs with view to achieve control of the pulmonary hematopoiesis . the usual sites of extramedullary hematopoiesis are the liver , spleen and intrathoracic paraspinal regions ( 3 ) . lungs and pleura are rare sites of extramedullary hematopoiesis with less than forty cases of pulmonary extramedullary hematopoiesis described in the current literature ( 4 ) . a causal association between pulmonary hematopoiesis leading to dyspnea and pulmonary hypertension has been postulated in few case reports and a limited number of cohort studies ( 1 , 2 , 5 ) . ( 1 ) listed hematopoietic infiltration of the pulmonary parenchyma as one of the probable causes of pulmonary hypertension in patients with myelofibrosis . ( 6 ) described the case of a 49-year - old man in whom dyspnea due to pulmonary hematopoiesis was a presenting feature of myelofibrosis . in most of case reports describing pulmonary extramedullary hematopoiesis , the diagnosis was suspected on the chest ct scan due to abnormalities such as ground - glass opacities ( 4 ) or interstitial septal thickening ( 6 ) . ground - glass opacities per se are non - specific ct findings with more common differentials of congestive cardiac failure and lung infection in patients presenting with dyspnea . in the setting of myelofibrosis , additional possibilities include pulmonary extramedullary hematopoiesis , thromboembolism or chemotherapy - induced lung toxicity ( 7 ) . in our case , an increased lung uptake of tc-99 m sulfur colloid is not specific to an extramedullary pulmonary hematopoiesis . it can occur after liver and bone marrow transplantation , hepatic veno - occlusive disease , liver cirrhosis , liver metastases or hepatic chemotherapy toxicity ( 8) . a possible mechanism is the stimulation of reticulo - endothelial elements in the lung interstitium or an induction of pulmonary macrophages . the localization of increased tracer activity in the lungs was sufficiently demonstrated on spect / ct imaging . in addition , spect / ct imaging also aided in confirming absence of tracer activity within the pleural spaces , thus excluding any pleural site of extramedullary hematopoiesis . we believe that spect / ct imaging , if available , should be included in the imaging protocol of suspected pulmonary hematopoiesis , as it can localize tracer activity in the lungs or pleura , which is not possible on a two - dimensional planar imaging . a histopathological confirmation of pulmonary hematopoiesis could not be obtained as a lung biopsy was not performed in our patient . however , pulmonary hematopoiesis was considered the most likely diagnosis in the absence of other complicating factors which could have resulted in an increased lung uptake of tc-99 m sulfur colloid . in summary , extramedullary pulmonary hematopoiesis in myelofibrosis leading to pulmonary hypertension and tricuspid regurgitation is a rare condition . this case report highlights the utility of tc-99 m sulfur colloid bone marrow scan in cases of unexplained pulmonary hypertension with underlying myeloproliferative disorders . we believe that an inclusion of spect / ct imaging helps to confirm and characterize the pulmonary involvement .

extramedullary pulmonary hematopoiesis is a rare entity with a limited number of case reports in the available literature only . we report the case of a 66-year - old man with known primary myelofibrosis , in whom a technetium-99 m sulfur colloid bone marrow scan with single - photon emission computed tomography ( spect)/ct revealed a pulmonary hematopoiesis as the cause of pulmonary hypertension and severe tricuspid regurgitation . to the best of our knowledge , this is the first description of technetium-99 m sulfur colloid spect / ct imaging in this rare condition .

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a 70-year - old female with oculocutaneous albinism , presented with proptosis of the right eye for 15 days and defective vision of both eyes since birth , which got worsened in the right eye for the past 15 days . ophthalmological examination revealed visual acuity of hm and 20/400 in re and le , respectively . eccentric proptosis of right eye was seen ( 27 mm hertel in re and 15 mm hertel in le ) with fullness in the superotemporal quadrant of the right orbit [ fig . 1 ] . anterior segment of both eyes showed iris transillumination defects , a normal pupillary reaction and nuclear sclerosis . proptosis of right eye in oculocutaneous albinism ultrasound of right eye showed low to moderate echogenic mass in the superotemporal quadrant of the orbit . 2 ] computed tomography ( ct ) and magnetic resonance imaging ( mri ) of orbit showed a well - defined lobulated , elongated mass of mixed intensity , measuring 7.1 3.6 2.8 cm with well - enhancing solid and non - enhancing cystic areas in the superior part of the right orbit . superiorly there was erosion of roof of the orbit with intracranial and extra dural extension . there was erosion of medial wall of the orbit with extension into the posterior ethmoidal sinus [ figs . 3 and 4 ] . imaging features were in favor of orbital neurofibroma , so radiologist suggested fine needle aspiration cytology or biopsy to confirm the diagnosis . however , they could not guarantee a total extirpation of the intracranial part of the plexiform neurofibroma . b - scan shows orbital mass indenting the eye ball ct orbit shows cystic mass with peripheral enhancement extending into cavernous sinus with eroding lesser wing of sphenoid bone mri orbit shows mass with cystic space extending into cavernous sinus histopathological study reveals plexiform neurofibroma h and e , 10 ) neurofibromas of the orbit are rare and account for 0.6 - 2.4% of all orbital tumors . plexiform neurofibromas , the most common orbital subtype , occur exclusively in neurofibromatosis type 1 . diffuse neurofibromas are usually the dermal variants ; they rarely affect the orbit and are clinically indistinguishable from the plexiform subtype . histologically , diffuse neurofibromas show greater cellularity , less collagen deposition , and lack the cellular peri - neural sheathing characteristic of plexiform neurofibromas . both the plexiform and diffuse subtypes lack clear margination and tend to be highly vascular . they are relatively well circumscribed and much less vascular . though this patient was diagnosed to have plexiform neurofibroma of the orbit , other clinical manifestations of neurofibromatosis 1 were absent . isolated plexiform neurofibromas without the systemic features of neurofibromatosis 1 have been reported at other anatomical sites ; however , their location in orbit is relatively rare . similar cases of orbital plexiform neurofibromas without the systemic features of neurofibromatosis 1 have been reported in literature . oculocutaneous albinism is associated with syndromes such as prader willi syndrome , angelmann syndrome , hermansky pudlack syndrome and chediak - higashi syndrome . a very rare case has been reported showing the genetic associations between partial albinism and neurofibromatosis in two daughters of a family along with axenfield 's defect , congenital deafness and peroneal muscular dystrophy . however , isolated orbital plexiform neurofibroma in association with albinism has not been reported so far . this rare case is reported for the coincidental presentation of oculocutaneous albinism and isolated orbital plexiform neurofibroma without any systemic features of neurofibromatosis 1 in the same patient and probably the first case to be reported .

a 70-year - old female patient presented with proptosis of right eye for the past 15 days and defective vision in both eyes since birth . she was found to have eccentric painful proptosis of right eye along with features of oculocutaneous albinism . eccentric proptosis was due to an orbital mass which proved to be a plexiform neurofibroma by histopathological examination . the case is presented for its rarity , as an isolated orbital plexiform neurofibroma without the systemic features of neurofibromatosis is rare and its coincidental presentation with oculocutaneous albinism is yet rare and has not been reported so far .

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we are also grateful to darby proctor for useful comments on a previous version of the manuscript . the present study was approved by the ethics committee of azabu university ( japan ) ( no . 1303042 ) . this research was supported by the jsps research fellowships for foreign researchers ( no . p10311 ) and the mext grant - in - aid for scientific research ( no . 26380981 ) to t. r. , the mext grant - in - aid for challenging exploratory research ( no . 23650132 ) to t. h. , and the grant - in - aid for scientific research on innovative areas ( no .

in a recent paper,1 we examined whether oxytocin in the domestic dog modulates the maintenance of close social bonds in non - reproductive contexts . we found that exogenous oxytocin promotes positive social behaviors not only toward conspecifics , but also toward human partners . here we examined in further detail the effect that oxytocin manipulation has on social play . when sprayed with oxytocin , subjects initiated play sessions more often and played for longer periods of time than when sprayed with saline . furthermore , after oxytocin nasal intake dogs displayed play signals more often than after saline administration , suggesting that oxytocin enhances dogs ' play motivation . to our knowledge , this study provides the first evidence that oxytocin promotes social play in the domestic dog . we use these results to hypothesize on the potential therapeutic use of oxytocin for promoting social behaviors and treating social deficits in the domestic dog .

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a 68-year - old male presented complaining of sudden and profound loss of central vision in his left eye following blunt eye trauma . he reported seeing a large , dense , central scotoma that began fading 1 h after the injury . he was emmetropic , phakic , and had no significant ophthalmic history . on examination , 24-h postinjury , best - corrected visual acuity ( bcva ) in the left eye oct of the left macula ( spectralis , heidelberg engineering , 5-line raster acquisition protocol ) revealed abnormal hyper - reflectivity and nodularity of the photoreceptor os layer . interestingly , the patient was found to have prominent abnormalities on infrared imaging using the infrared reflectance protocol of the spectralis oct [ fig . 1 ] . infrared imaging of the left fundus revealed diffuse infrared hypo - reflectance dotted with spots of very low pixel value ( dark ) , creating a stippled appearance . point - to - point correlation between the infrared and oct images using the spectralis software ( heidelberg engineering , germany ) demonstrated that the infrared dark spots correlated with foci of thickened os seen on 5-line raster oct . no pathology of the superficial retina , retinal pigment epithelium or choroid was detected using red - free reflectance , fundus auto - fluorescence , and enhanced - depth imaging ( edi ) , respectively . 30 posttrauma , and at 8 months posttrauma , bcva in the left eye was 20/25 and the retina appeared normal on examination and when imaged with infrared reflectance , 5-line raster oct , fundus auto - fluorescence , and edi [ fig . 2 ] . left fundus images at day 1 postblunt trauma to the left eye . ( b ) infrared confocal scanning laser ophthalmoscope fundus image demonstrating stippled hypo - reflectance at the macula . ( c ) optical coherence tomography of the macula demonstrating abnormal hyper - reflectivity of the outer segments ( between arrowheads ) . ( b ) infrared confocal scanning laser ophthalmoscope fundus image reveals resolution of the infrared hypo - reflectance in this case , there is a clear temporal relationship between eye trauma , transient vision loss , transient oct changes consistent with cr , and transient infrared hypo - reflectance . cases of cr detectable on oct , but not fundus examination have been described , confirming that some cases of cr are subclinical . to the best of the authors knowledge the pathology of cr has been studied histologically and on oct , and comprises fragmentation of the photoreceptor os without injury to the inner retina . as demonstrated by our case , this manifests on 5-line raster oct as abnormal hyper - reflectivity of the os layer . this oct feature is subtle and is easily overlooked if the study is not carefully scrutinized . our case implicates infrared imaging as a diagnostic adjunct for detecting subclinical cr . since focal dark spots on infrared imaging correlated with points of nodular os thickening in our case , we infer that the infrared hypo - reflectance in cr is caused by increased absorption of infrared light by an abnormal os layer . with a wavelength of 820 nm , the infrared mode of the spectralis oct penetrates deeper into the retina than modalities using visible wavelengths of light . it is , therefore , useful for detecting outer retinal pathology , such as that of cr . the spectralis uses a confocal scanning laser ophthalmoscope ( cslo ) and records infrared reflectance without barrier filters . compared with conventional recording techniques , cslo improves image resolution by using a higher emission of light energy and by reducing the capture of scattered light . further studies are required to determine whether infrared hypo - reflectance is a consistent feature in all cases of cr , and whether this imaging modality has greater sensitivity for detecting subclinical cr than 5-line raster oct . nevertheless , this case suggests that infrared imaging may have a role as a diagnostic adjunct for detecting subclinical cr . we recommend that clinicians consider performing infrared imaging of the retina when managing a patient who presents with unexplained vision loss after blunt trauma and a normal - appearing fundus .

commotio retinae ( cr ) is an outer retinal disorder following blunt trauma to the eye . histologically it is characterized by disruption of the photoreceptor outer segments ( os ) , typically without injury to other retinal layers . using spectral - domain optical coherence tomography ( oct ) the condition is visible as hyper - reflectivity of the os . most cases of cr are associated with transient grey - white discoloration of the retina and are easily diagnosed clinically , but there have been reports of oct - confirmed cr without retinal discoloration . it is likely that this subclinical variant of cr is under - recognized as the oct features of cr are subtle . here , we report a case of oct - confirmed subclinical cr that demonstrated prominent infrared hypo - reflectance , using the infrared protocol of the spectralis oct , heidelberg engineering . this case suggests that infrared reflectance may have a role in diagnosing cases of subclinical cr .

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a 52-year - old woman with granulocytic sarcoma affecting the anterior cranial fossa and frontal sinus was commenced on ade ( cytarabine , daunorubicin and etoposide ) and mylotarg ( gemtuzumab ) through a peripherally inserted central catheter ( picc ) line as part of the aml 17 trial ( http://aml17.cardiff.ac.uk/aml17/default.aspx ) . she was known to have a beta - lactam allergy manifest as an erythematous rash . on day 9 of chemotherapy , her fever resolved after 48 hours and meropenem was stopped after 7 days . on day 18 of chemotherapy she remained febrile over the next three days and caspofungin was started in view of high - resolution computed topography ( hrct ) chest findings compatible with possible fungal infection and a positive initial serum galactomannan assay ( although the repeat specimen was negative ) . meropenem was therefore replaced with ciprofloxacin as it was thought to be responsible for the rash . all cultures including multiple blood cultures and picc line site swabs were culture negative . on day 31 of chemotherapy she was still febrile and blood cultures from peripheral veins and the picc line taken on day 30 yielded gram - positive cocci in pairs and chains after 24 and 11 hours ' culture respectively . the isolate was identified as leuconostoc lactis using the bd phoenix identification ( becton , dickinson and company , usa ) and api rapid i d 32 strep systems ( biomrieux , france ) . mean inhibitory concentrations ( mics ) determined by e - test ( ab biodisk , sweden ) were : penicillin 0.5 mg / l , vancomycin > 256 mg / l , teicoplanin 256 mg / l , ciprofloxacin 1.0 mg / l , tigecycline 0.064 mg / l , linezolid 1.5 mg / l and daptomycin 0.064 mg / l . on day 32 of chemotherapy , ciprofloxacin and teicoplanin the next day therapy was changed to tigecycline ( 50 mg iv q12h ) because of concerns over myelotoxicity ( anaemia and thrombocytopenia ) associated with linezolid . daptomycin was unavailable in the hospital formulary and ampicillin was not used due to concerns over beta - lactam allergy and a borderline penicillin e - test mic . the patient continued to have low - grade fevers over the next four days , despite a negative transthoracic echocardiogram . on the fourth day of treatment , however , her fever resolved and she was discharged from hospital after completing 8 days of tigecycline , to which she had no adverse effects . leuconostoc spp . are catalase - negative , gram - positive , facultatively anaerobic coccobacilli . they are environmental organisms often found on plants , dairy products , vegetables , wine and occasionally in human vaginal and stool samples . although an uncommon human pathogen , cases of bacteremia , endocarditis , pneumonia , meningitis , osteomyelitis , peritonitis , brain and liver abscesses have been described . and other gram - positive antimicrobial - resistant organisms are increasingly recognised as important pathogens in neutropenic patients probably due , in addition to immunosuppression , to the use of indwelling intravascular devices , antibiotic prophylaxis and evolution of chemotherapeutic agents . infection with leuconostoc may cause fever , intravenous catheter - related sepsis , bacteremia , abdominal pain , gastroenteritis , colitis or meningitis in this group of patients . other reported risk factors for infection removal of intravenous catheters alone has been shown to be curative in some patients without the need for antimicrobial therapy . are intrinsically resistant to glycopeptides , owing to the production of peptidoglycan precursors ending in d - ala - d - lac , but are usually susceptible to penicillin , ampicillin , aminoglycosides , clindamycin , minocycline and macrolides . in addition , linezolid and daptomycin have been used successfully to treat leuconostoc bacteremia , although linezolid mics of leuconostoc spp . although the organism has been shown to be resistant to cefoxitin , it is susceptible to cefotaxime in vitro . tigecycline , a glycylcycline , is a broad spectrum synthetic derivative of minocycline which has a broad spectrum of activity against various gram - positive and gram - negative bacteria including multidrug - resistant strains , anaerobic bacteria and atypical organisms . it has proven to be useful in the treatment of hospital - acquired infections caused by vancomycin - intermediate and vancomycin - resistant enterococci ( vre ) , meticillin - resistant staphylococcus aureus ( mrsa ) , extended - spectrum -lactamase ( esbl)-producing enterobacteriaceae , multidrug - resistant acinetobacter baumanii and penicillin - resistant streptococcus pneumoniae . in the uk , its licensed indications are complicated intra - abdominal and complicated skin and soft tissue infection . it is also licensed for the treatment of community - acquired pneumonia in the us . although tigecycline has been demonstrated to be a safe and effective second - line option in microbiologically documented infections in neutropenic patients , there have been no trials to determine whether tigecycline is effective in neutropenic bacteremia and there are also theoretical concerns surrounding low serum concentrations ( due to a large volume of distribution ) and its mostly bacteriostatic activity . it is for this reason that tigecycline is not generally recommended for primary bacteremia but it is used for secondary bacteremia associated with complicated skin and soft tissue infections , intra - abdominal infections and community - acquired pneumonia . despite these concerns , here we report the first successful use of tigecycline in the treatment of leuconostoc bacteremia in a neutropenic patient .

leuconostoc lactis is a recognised cause of infection in immunocompromised hosts . it is intrinsically resistant to multiple antibiotics and treatment options may be limited . we report a case of safe and effective use of tigecycline in the treatment of leuconostoc catheter - related line sepsis in a neutropenic patient . to our knowledge , this is the first reported case of successful use of tigecycline for leuconostoc bacteremia .

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extraskeletal soft tissue chondroma is a very rare , slow - progressing , benign tumour . chondromas are tumour - like masses formed by proliferation of chondrocytes in a mature hyaline matrix . a 22-year - male came with chief complaints of asymptomatic swelling on the palate since birth . he had symptoms of cleft palate , i.e. , nasal regurgitation and poor speech . on examination , there was a complete cleft of secondary palate and the cleft was filled by non - tender , globular swelling of size 3 sq . there was a linear band of soft tissue extending from the anterior part of the swelling to the upper lip mucosal surface after passing through the diastasis of the upper central incisors [ figure 1 ] . pre - operative photograph showing palatal swelling completely obliterating the cleft with linear band extending to the lip on computed tomography scan , a 30 mm 28 mm size , well - defined , globular soft tissue mass was seen in the region of the hard palate , which showed fusion defect anteriorly . plain computed tomography coronal section of the swelling differential diagnosis of dermoid cyst and chondroma were kept . intraoperatively , the tumour was seen attached by a small pedicle to the nasal mucosa of the cleft margin on the right side . the tumour was excised along with the linear band of tissue extending to the mucosal surface of the upper lip [ figure 3 ] . histopathological examination revealed hypercellular lobules of cartilage composed of evenly spaced chondrocytes of uniform size and separated by collagen and adipose tissue . there was no recurrence after 2 years of follow - up [ figure 5 ] . histopathological appearance of the chondroma two - year follow - up photograph showing repaired palate having adequate length with no recurrence soft tissue chondromas are benign cartilage - forming tumours that are usually found in close proximity to the tendon or joint capsules . only five cases of soft tissue chondroma of palate have been reported in the literature.[36 ] it has never been reported in a patient of cleft palate . one theory is that these lesions are from residual embryonal tissue ( embryonic remnant theory ) . the other theory is that these lesions are from metaplasia of pluripotential mesenchymal cells ( metaplastic theory ) . in our case , because the swelling was present since birth , this goes in favour of embryonic remnant theory . even after a meticulous review of the literature , we could not establish the cause and effect relationship between chondroma and cleft palate . in fact , we feel that the embryonic changes in the palate during the process of cleft might lead to entrapment of mesodermal tissue ( mesoderm giving rise to cartilage / bone ) . clinically , these tumors present as slow - growing , firm masses not attached to the underlying bone and are , occasionally , painful . radiologically , soft tissue chondroma show well - demarcated , extraskeletal , soft tissue masses .

soft tissue chondroma of palate is very rare . it has never been reported in a cleft palate patient . we report a case of 22-year - old male who came with asymptomatic swelling on the palate since birth , along with complete cleft of secondary palate . he had symptoms related to cleft palate only , i.e. , nasal regurgitation and speech abnormalities . swelling was excised and the cleft palate was repaired . histopathological examination revealed chondroma of the palate . the patient had no recurrence after 2 years of follow - up .

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a 36 year old , para 2 female with a history of chronic right adnexal pain was admitted for a laparoscopic right salpingo - oophorectomy . the patient experienced worsening right ovarian pain which did not improve despite nonsteroidal anti - inflammatory medications . an ultrasound revealed a 4 cm complex ovarian mass which did not change in size with serial ultrasounds . previous surgeries included an abdominal hysterectomy for a fibroid uterus , laparoscopic left salpingooophorectomy and lysis of adhesions for pelvic pain , an appendectomy , two previous cesarean sections , a bilateral tubal ligation and an inguinal herniorrhapy as a teenager . the patient underwent general endotracheal anesthesia and was prepped and draped in the usual manner after being placed in the dorsolithotomy position . after making a small incision in the umbilicus , a veress needle with its 2 mm trocar was carefully inserted into the abdomen with the panniculus elevated . the saline drop test revealed patency , and the veress needle was attached to the co2 for the pneumoperitoneum . the co2 was immediately stopped , the veress needle removed and a 2 mm microlaparoscope ( minisite gold ; u.s . surgical corp . , norwalk , ct ) inserted into the trocar , which revealed bowel lumen with stool . a second 2 mm trocar was placed in the right lower quadrant , and the microlaparoscope revealed a perforation into the anti - mesenteric border of the ileum . was inserted under direct visualization lateral to the right rectus muscle at the level of the umbilicus . the 2 mm umbilical trocar was replaced with a new one of the same diameter . at the site of the small bowel entry , after irrigating the pelvic and abdominal cavities with 3 liters of normal saline with no further fecal spillage or bleeding , the decision was made to not suture the site of entry into the small bowel . postoperatively , the patient had a nasogastric tube inserted , was placed on famotidine ( pepcid ) 20 mg every 12 hours and was given antibiotics consisting of ampicillin , gentamicin and clindamycin intravenously . on the evening of surgery , the patient developed a fever of 101.2 degrees fahrenheit . on postoperative day one , she had a single temperature spike of 100.9 after being afebrile . on postoperative day three , she had a small bowel movement , was advanced to a regular diet and discharged home in the afternoon on oral cephalexin . at her one week postoperative visit she remained afebrile , tolerating her diet and with no complaints . one month after surgery she was symptom free and her chronic right adnexal pain was gone . most of the current data on laparoscopic complications is based on case reports and small series . open laparoscopy was developed to reduce the risk of blind entry into the peritoneal cavity . however , injury to the bowel has been reported to occur at the same rate with this technique . recent advances in microlaparoscopy have allowed us to perform both diagnostic and operative procedures through 2 mm trocars . in our patient , a microlaparoscope inserted through the entry site confirmed the complication . had we performed traditional laparoscopy using a 10 mm trocar , the site of bowel injury would have required suturing , possibly a laparotomy . in cases where the site of perforation is free of adhesions and in need of repair , the bowel can be sutured externally by withdrawing the bowel through a 12 mm trocar . our minimally invasive , conservative approach to this complication was possible because no further fecal material leaked through the site of perforation and the diameter of the injury was small . we felt that suturing in this case was unnecessary because the margins were regular , hemostatic and self - sealing . the stool that was forced through this site probably was a result of the increased intraluminal pressure in the bowel from the co2 insufflation . after copious irrigation with normal saline and no further spillage , we felt that the patient 's morbidity would be greater with suturing of the bowel if it produced bleeding or further spillage . except for an initial fever , the patient responded well to conservative management with bowel decompression , antibiotic therapy and close observation . conditions requiring a laparotomy following a bowel perforation include any sign of peritonitis , persistent fever , ileus or prolonged vomiting . we believe that some small bowel perforations from 2 mm instrumentation can be managed conservatively without suturing provided that the site of injury is not actively leaking stool nor bleeding .

although laparoscopy is one of the most common surgical procedures done today , bowel perforations can and do occur during the initial insertion of the veress needle and/or trocar . recent advances in microlaparoscopy have reduced the morbidity of this complication when encountered . we report a case of small bowel perforation following insertion of a veress needle with its 2 mm trocar and our minimally invasive intra - operative and postoperative management of the patient .

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the article " efficacy of and tolerance to mild induced hypothermia after out - of - hospital cardiac arrest using an endovascular cooling system " by pichon et al . in the previous issue of critical care only 10% of patients undergoing out - of - hospital cardiopulmonary resuscitation are discharged alive from the hospital . this high mortality is to a major part due to ischaemic brain damage . in 2002 , a european multicentre trial on the use of mild therapeutic hypothermia as well as other clinical trials clearly demonstrated a decrease in mortality and a better neurological outcome in cardiac arrest patients . only six patients have to be treated to save one life ( number needed to treat = six ) . this is far better than with most other expensive approaches in the intensive care unit ( icu ) . consequently , therapeutic hypothermia has been recommended in an advisory statement by the international liaison committee on resuscitation ( ilcor ) already in 2003 . in 2005 , the european resuscitation council ( erc ) guidelines stated : 1 . unconscious adult patients with spontaneous circulation after out - of - hospital ventricular fibrillation cardiac arrest should be cooled to 32 to 34c . cooling should be started as soon as possible and continued for at least 12 to 24 hours . 2 . induced hypothermia might also benefit unconscious adult patients with spontaneous circulation after out - of - hospital cardiac arrest from a non - shockable rhythm , or cardiac arrest in hospital . 3 . a child who regains a spontaneous circulation but remains comatose after cardiopulmonary arrest may benefit from being cooled to a core temperature of 32 to 34c for 12 to 24 hours . therapeutic hypothermia influences postresuscitation brain and other organ injury in many different ways : it reduces metabolism , free radical formation , intracellular calcium overload , as well as translation and transcription of pathogenic proteins . additionally , it has anti - apoptotic , anti - inflammatory and anti - coagulatory properties and can reduce oedema formation . there are few areas in emergency and intensive care medicine where scientific evidence is so strong and where international guidelines are so clear . nevertheless , implementation of hypothermia is lousy . in most countries on both sides of the atlantic , under 30% of cardiac arrest patients are receiving hypothermia . colleagues are stating that they do not have enough information and experience , that this therapy is not evidence - based and that it is technically too difficult . mild therapeutic hypothermia is definitely underused post cardiac arrest , and many patients who need not die are dying because of this clinical reality . here pichon and colleagues report on the efficacy and tolerance of a commercially available intravascular cooling device used in 40 post cardiac arrest patients . cooling with this device was safe , relatively fast and effective in maintaining the targeted temperature . regardless of the initial cardiac rhythm about which the brain does not care all patient groups benefited from cooling with this device . maintenance of hypothermia is practicable with both surface and endovascular cooling . in the past , very recent data on different techniques of body surface cooling suggest that these techniques are also able to maintain body temperature in a clinically sufficient way . animal experimental data suggest that hypothermia is more effective the faster it is established after the arrest . therefore , the use of other and faster methods to induce hypothermia must be considered . infusion of ice - cold ringer 's solution ( 30 ml / kg within 30 minutes ) has been shown to be an easy , cheap , effective and safe way of inducing hypothermia in less than one hour . this is even possible in the out - of - hospital setting . for subsequent maintenance of hypothermia , intravascular and body surface cooling techniques well known side effects of therapeutic hypothermia , like hypokalaemia , hypomagnesaemia and bacteraemia may occur , and it is important to know this . major complications including arrhythmias , bleeding , pneumonia , sepsis et cetera , however , do not occur more often in hypothermic as compared to normothermic cardiac arrest patients . the most important ' side effect ' of hypothermia is that it is not used routinely in most cardiac arrest patients . according to hippocrates , we have to treat the next unconscious cardiac arrest patient with mild therapeutic hypothermia , regardless of which technique we are using . erc = european resuscitation council ; icu = intensive care unit ; ilcor = international liaison committee on resuscitation .

in 2005 , the european resuscitation council ( erc ) guidelines stated : unconscious adult patients with spontaneous circulation after out - of - hospital ventricular fibrillation cardiac arrest should be cooled to 32 to 34c for 12 to 24 hours . patients with cardiac arrest from a non - shockable rhythm , in - hospital patients and children may also benefit from hypothermia . there is no argument to wait . we have to treat the next unconscious cardiac arrest patient with hypothermia .

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minimal change nephropathy ( mcn ) accounts for 25% of adults presenting with a nephrotic syndrome . although most patients respond to corticosteroid therapy , a significant number relapse frequently and may present a real therapeutic difficulty . we present a case of apparently refractory relapsing mcn that was successfully treated with a combination of sirolimus and cyclosporin . in 1989 , a 35-year - old female presented acutely with heavy proteinuria ( 22 g/24 h ) and normal renal function . she was commenced on oral prednisolone ( 60 mg od ) , and achieved complete remission within weeks . however , multiple relapses followed on reduction of the corticosteroid dose . azathioprine , cyclosporin , mycophenolate mofetil , tacrolimus and chlorambucil were all tried unsuccessfully , but neither the relapse rate nor the steroid requirements improved . in 2003 , cyclosporin was re - introduced to minimize steroid exposure with trough plasma levels of 149 g / l . in the preceding 14 years , the prednisolone dose had rarely been below 15 mg / day , and there had typically been two to three relapses per year . in 2006 , sirolimus 2 mg / day was added to her prednisolone ( 15 mg / day ) , and cyclosporin ( 6 mg / kg / day)she was also prescribed primidone since childhood for epilepsy . at review , the trough plasma levels of cyclosporin and sirolimus were 153 g / l and 2.9 g / l , respectively . steroids were gradually reduced and subsequently completely discontinued 24 months after sirolimus was added with no relapses in the last 30 months . mcn is predominantly a steroid - responsive disease , with around 75% of adult patients achieving remission by 8 weeks . unfortunately , 3060% will suffer at least one episode of relapse and around 25% will do so more frequently . a variety of immunosuppressive medications , each with its own side effect profiles , have been trialled as steroid - sparing agents with variable success . frequently relapsing minimal change disease the first documented use of sirolimus in combination with tacrolimus as a therapeutic option in mcn was published in 2005 by patel et al . . in conclusion , we have detailed a case of relapsing mcn , which has only been controlled by the combined use of sirolimus and cyclosporin . this has not only resulted in the longest period of remission , but has also allowed for the discontinuation of corticosteroids . this is the second documented use of sirolimus in this manner that we are aware of and the first that has trialled the combination of sirolimus and cyclosporin .

minimal change nephropathy ( mcn ) accounts for around 25% of adults presenting with a nephrotic syndrome . although most patients respond to corticosteroid therapy , a significant number relapse frequently and may present a real therapeutic difficulty . we present a case of apparently refractory relapsing mcn that was successfully treated with a combination of sirolimus and cyclosporin , resulting in the longest period of steroid free remission that the patient has ever experienced . to our knowledge , this is the first documented use of this combination in this manner .

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a 43-year - old woman diagnosed with intravenous leiomyomatosis at another hospital was transferred to our hospital . she had suffered from palpitation , dizziness , dyspnea , and chest pain for two weeks prior to admission into another hospital , and had experienced syncope three times on the day of admission to our hospital . no cardiac murmur was noted , and laboratory findings were unremarkable with the exception of anemia ( hemoglobin : 9.7 g / l ) . cardiac and pelvic magnetic resonance imaging ( mri ) taken at the previous hospital revealed multiple low attenuation masses in the uterus , involving both ovaries , the left gonadal vein , the left internal iliac vein , and the left renal vein , which extended into the inferior vena cava ( ivc ) , and to the right atrium ( ra ) ( fig . 1 ) . a trans - thoracic echocardiogram revealed a 4.81.8-cm hypermobile and echogenic mass in the ra connected to the mass in the ivc . emergency one - stage operation was planned with a gynecologist , and upon being transferred to the operation room , the patient had a sudden onset of dyspnea and unstable blood pressure . rapid endotracheal intubation was performed to maintain blood oxygen saturation . in transesophageal echocardiography ( tee ) , the echogenic mass in the ra and ivc was not seen . we suggested that the mass detached from the ra and migrated to the right ventricle or the pulmonary artery . we discovered an echogenic linear mass in the pulmonary artery between the arterial bifurcation and both main pulmonary arterial branches ( fig . trans - abdominal hysterectomy and left salphingo - oophorectomy were performed through median laparotomy , and the mass in the left gonadal and internal iliac veins was completely removed ( fig . another mass in the pulmonary artery was also removed under conventional cardiopulmonary bypass without circulatory arrest ( fig . the ra was opened to confirm that there was no remnant mass in the ra and the ivc . the patient 's postoperative course was uneventful , and she has received follow - up care for two years without any evidence of tumor recurrence . intravenous leiomyomatosis is a benign intravascular proliferation of smooth muscle cells originating from the intrauterine venules and reaching the right heart . the uncommon benign tumor usually arises from either the uterine venous wall or uterine leiomyoma , and although it is histologically benign , it can cause fatal cardiovascular complications such as cardiac failure , pulmonary embolization , or sudden death . in previously reported cases describing intracardiac involvement , the tumor extended to the right atrium in 30% of cases , and to the right ventricle in 70% of cases . extension or embolization into the pulmonary artery or lung metastasis is a very rare complication constituting less than 5% of the reported cases . however , when it occurs , the course of the patient can be fatal , and urgent surgical correction is imperative . ariza and colleagues described the first successful two - stage removal of an intracaval mass , with delayed laparotomy after resection of the intracardiac portion of a tumor in 1982 . since then , a staged operation has been performed in many cases ( radical resections of intracavocardiac tumors and intrapelvic components in separate operations ) , but more recently , a one - stage approach by median sternotomy with cardiopulmonary bypass with or without hypothermic circulatory arrest , and a separate laparotomy has been performed successfully . the advantages of the one - stage resection include avoiding risks of tumor embolism , tumor progression , or hemodynamic complications in the interval between the two stages of two - staged operations . in addition , because both abdominal and thoracic cavities are opened , the tumor can be removed completely , and vascular reconstruction and bleeding control may be more easily performed . however , in hemodynamically unstable patients , the longer operative time may not be appropriate , and a two - stage operation may be beneficial . since incomplete resection of the tumor may causes recurrence , gathering detailed preoperative information regarding tumor localization , size , and extent by using abdominal ultrasound , echocardiogram , computed tomography , magnetic resonance imaging , and venography is required . transesophageal echocardiography should also be performed to detect possible changes in the location and size of the tumor , as occurred in this case . in conclusion , intracardiac leiomyomatosis should be considered in a female patient presenting with an extensive mass in the right side of the heart , and urgent surgical removal should be performed to avoid possible fatal complications , even if the patient is asymptomatic . as the tumor may move or detach from the central venous system even during operation , intraoperative tee

a 43-year - old woman was diagnosed with an intravenous leiomyomatosis at a previous hospital and transferred to our hospital to undergo surgical treatment . emergency one - stage operation for coincidental removal of intra - abdominal , right atrial , and intravenous masses were planned . upon arriving at the operating room , she suffered a sudden onset of severe dyspnea and showed hemodynamic instability . intraoperative tee showed pulmonary embolization of a right atrial mass . removal of the pulmonary artery mass and the intra - abdominal mass , and the cardiopulmonary bypass were performed without any complications .

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medical emergency teams ( mets ) and critical care outreach are no longer new ideas . the services were founded in australia in the 1990s with the concept of mets using the well - recognised principle that early recognition and aggressive intervention improves outcome from critical illness . the systems have now developed into a variety of incarnations around the globe becoming critical care outreach services ( ccos ) in the united kingdom , and the rapid response teams in north america [ 3 - 5 ] . although there are some differences between these services , they all have the same primary aim of preventing critical illness with its associated morbidity and mortality . ccos losing its youth produces an urgent requirement for efficacy and cost - effectiveness to be demonstrated . the most detailed evaluation to date of these systems is the merit study from australia , which was a multicentre cluster randomised trial of mets . sadly , the study failed to demonstrate a reduction in intensive care unit ( icu ) admissions , cardiac arrests or inhospital mortality . there are some weaknesses in the trial but it still represents by far the highest level of evidence to date on mets / ccos . the publication of this disappointing result led to a rapid distancing of ccos from their met parent , clearly fearing that this result would tarnish their new - found status . indeed , since the publication of the merit study , proponents of ccos have commonly stated that ccos can not be tested using a randomised controlled trial design , and some proponents seemed to believe that supportive evidence was not required at all . thankfully , in the previous issue of critical care a detailed evaluation of ccos in the united kingdom from a group based at the intensive care national audit & research centre in london was published . in the paper the authors restate the principle that ' ccos can not now be evaluated using the gold - standard research design , a multicentre , randomised controlled trial ' , and instead one must use an interrupted time - series method . the analysis was performed on the intensive care national audit & research centre case - mix programme ( a high - quality clinical database of nearly 400,000 icu admissions ) and on data taken from a large national survey of ccos . a range of outcomes designed to ' reflect the ccos objectives of averting admissions , ensuring timely admission and enabling discharge were investigated ' , including the proportion of admissions direct from wards , the length of icu stay , icu mortality and hospital mortality . sadly , despite reductions in cardiopulmonary resuscitation rates and physiological disturbance in the time before icu admission , ccos were not associated with an improvement in icu mortality or hospital mortality . further , the authors were unable to identify which of the many highly variable operational characteristics of the ccos were optimal . interestingly , they observed that there was no ' dose response ' relationship for ccos that could have implied that the greater the ccos coverage , the better the outcomes that can be achieved . finally , the authors observed that ' ... changes in admission characteristics may be attributable in part to the use of physiological track and trigger warning systems ' , despite the fact that this group 's previous work demonstrated very poor sensitivity and specificity for such scores . so where does this leave us with regard to future of ccos in the united kingdom and beyond ? the continued inability of studies to demonstrate the efficacy of ccos and a complete lack of evidence for cost - effectiveness is worrying . a recent guideline by the national institute for health and clinical excellence on the management of the acutely ill hospital patient was unable to recommend outreach services due to a lack of supportive evidence . the national institute for health and clinical excellence did feel able to recommend the use of early warning scoring systems but was unable to identify a particular system or cutoff points due to the lack of evidence of accuracy for these scores in clinical practice . despite the lack of evidence , the institute of healthcare improvement recommends ' deploying rapid response teams ' as one of their 12 interventions ' proven to prevent morbidity and mortality ' in their 100,000 lives campaign . the institute of healthcare improvement clearly has access to an evidence base that the rest of us do not . do early warning systems actually allow early identification of sick patients , or are their diagnostic accuracies too low to justify use in clinical practice ? 2 . is there an optimal configuration for ccos that can actually lead to an improvement in important patient - based outcomes ? 3 . if ccos can be demonstrated to be efficacious will it prove to be cost - effective ? should countries that fund ccos now disinvest and spend these resources in more effective ways ? ccos = critical care outreach services ; icu = intensive care unit ; met = medical emergency team .

an evaluation of critical care outreach services was published in the previous issue of critical care that fails to demonstrate any important outcome benefit associated with these services . it is now time to ask some difficult questions about the future of outreach , including whether the lack of evidence should lead to disinvest - ment in such services .

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giant cell tumor ( gct ) of bone is a relatively common benign bone lesion . gcts are usually located in long bones , and most lesions are found around the knee . although gcts have been observed in other less frequent sites , such as the patella , great trochanter , and skull ; involvement of the olecranon we present a case of solitary gct of bone in the olecranon that was confirmed by preoperative needle biopsy and postoperative histological examination . therefore , the treatment included intralesional curettage , allogeneic bone grafting , and plating . at 26 months follow - up , the patient had no local recurrence . informed written consent was obtained from the patient for submission of the data for publication . an approval from the institutional review board a 32-year - old female was admitted to the first hospital of jilin university of changchun with a complaint of left elbow pain after a minor injury . upon physical examination , obvious tenderness was observed at her left olecranon , but no soft tissue mass was palpated . anteroposterior and lateral plain radiographs showed an expansile lytic lesion located in the left olecranon and extending into the subchondral region and the coronoid process . cortical breach was also identified in the dorsal aspect of the olecranon , suggesting a pathological fracture as a source of the pain . magnetic resonance imaging ( mri ) showed no soft tissue extension [ figure 2 ] , but the tumor had broken through the subchondral bone and extended into the elbow joint . anteroposterior and lateral plain radiographs showing an expansile lytic lesion located in the left olecranon and extending into the subchondral region and the coronoid process . note the pathological fracture in the dorsal aspect of the olecranon ( white arrow ) magnetic resonance imaging ( mri ) showing a relatively well - defined lesion of hyperintensive signals in a t2-weighted image , and no soft tissue extension the differential diagnosis included gct of bone , solitary bone cyst , metastasis , and brown tumor of hyperparathyroidism . a fine needle was positioned in the pathological fracture area along the operative incision after the administration of local anesthesia . a needle biopsy was then performed and a gct of bone was identified by pathological section . in order to prevent local recurrence , en bloc resection surgery was proposed , but the patient refused . thus , the patient was managed with intralesional curettage , allogeneic bone grafting , and plating . during the operation , gross findings of the tumor indicated that it was soft in texture and yellow in color . histology revealed that the tumor was composed of mononuclear ovoid and spindle - shaped cells associated with multinucleated giant cells and macrophages . this appearance was characteristic of gct of bone [ figure 3 ] . at the 26-month follow - up , the patient did not present with any local recurrence . histological analysis showing that the tumor was composed of mononuclear ovoid and spindle - shaped cells associated with multinucleated giant cells and macrophages . in addition , patients with gcts of bone present most often in the 3 or 4 decade of life . most gcts arise in metaphysical - epiphysical areas and are most commonly found in the distal femur , proximal tibia , and distal radius . other less frequent sites include the proximal femur , vertebral bodies , distal tibia , proximal fibula , hand , and wrist . in addition , gcts occurring in the patella and great trochanter have been reported . in several large studies , a total number of 1,447 gct of bone cases has been reported , but none of them were located in the olecranon . , reported one patient with multicentric gcts involving the left proximal ulna from a 12 year retrospective study conducted at the mayo clinic . to the best of our knowledge , the olecranon ossific nucleus first appears around 9 years of age and fuses completely by 12 - 15 years of age , which is relatively earlier than other long bones . the radiographic appearance of gct is usually characteristic of the disease and may be sufficient for making a correct diagnosis . however , in this case , although the plain films showed characteristic findings of gct , it was difficult to make a definitive conclusion . this was largely due to the rare location of the lesion , and the olecranon is a rare area for neoplasms to occur . only a few cases involving this anatomical region a brown tumor resulting from hyperparathyroidism also presents with similar radiographic features as this type of tumor . however , the clinical course and x - ray examination of this case excluded those differential diagnoses . other than the eccentric location , the lesion in this case had characteristics that were similar to lesions in bones with a smaller diameter , such as the proximal fibula . intralesional curettage has been the preferred treatment for most cases of gct of bone , despite a higher incidence of local recurrence . the use of local adjuvants , such as liquid nitrogen , bone cement , and hydrogen peroxide , may reduce the rate of local recurrence . radiotherapy has also been used to treat gct of bone in order to decrease local recurrence and is especially useful for treating difficult locations , such as the spine and sacrum . gct of bone is a relatively common benign bone lesion that is usually located in long bones , while involvement of the olecranon is extremely rare .

giant cell tumor ( gct ) of bone is a relatively common benign bone lesion and is usually located in long bones , but involvement of the olecranon is extremely rare . here , we present a case of solitary gct of bone in the olecranon that was confirmed by preoperative needle biopsy and postoperative histological examination . the treatment included intralesional curettage , allogeneic bone grafting , and plating . at 26 months follow - up , the patient had no local recurrence .

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the 2 huvec cell lines used in the study were derived from male caucasian donors genotyped as heterozygotes for the 9p21 cad associated snps . the 4 ebv transformed lymphoblastoid cell lines ( lcl ) were selected for their genotypes ( 2 homozygous cad risk or 2 homozygous cad non - risk ) using the hapmap data27 . experiments were performed within 24 passages by treating cells with 100 ng / ml of ifn ( r&d ) for 24 hrs . treated and untreated cells were subjected to rt - pcr ( huvec ) , chip ( huvec and lcl ) , 3c analysis ( huvec ) or fish ( huvec ) . probe design : we designed 12 acceptor probes in the interval chr9:22100523 - 22126469 ( hg18 ; spanning from ecad7 to the et2d2 enhancer ) , on both strands immediately 3 of the 6 bamhi sites in the region . we designed 290 donor probes on both strands immediately 5 of the 145 bamhi sites in the interval chr9:21035934 - 22494089 ( hg18 ; except where acceptor probes were designed ) . a universal sequence added to the probes is compatible with illumina ga adapters for direct sequencing . the 12 acceptor probes and 290 donor probes ( supplemental table 8) were pooled in equimolar amounts , separately . 3d - dsl sequencing : the dsl ligation products were prepared as described in kwon et al.23 . 3c was performed as per lieberman - aiden et al 28 and the products were sheared by sonication . donor and acceptor probes pools were annealed to the biotinylated 3c samples and the biotinated dna was bound on to streptavidin magnetic beads . the 5 phosphate of acceptor probes and 3 oh of donor probes were ligated using taq dna ligase . the ligated products were washed and eluted from the streptavidin magnetic beads , followed by pcr amplification and deep sequencing on the illumina ga2 ( supplemental information ) . the 2 huvec cell lines used in the study were derived from male caucasian donors genotyped as heterozygotes for the 9p21 cad associated snps . the 4 ebv transformed lymphoblastoid cell lines ( lcl ) were selected for their genotypes ( 2 homozygous cad risk or 2 homozygous cad non - risk ) using the hapmap data27 . experiments were performed within 24 passages by treating cells with 100 ng / ml of ifn ( r&d ) for 24 hrs . treated and untreated cells were subjected to rt - pcr ( huvec ) , chip ( huvec and lcl ) , 3c analysis ( huvec ) or fish ( huvec ) . probe design : we designed 12 acceptor probes in the interval chr9:22100523 - 22126469 ( hg18 ; spanning from ecad7 to the et2d2 enhancer ) , on both strands immediately 3 of the 6 bamhi sites in the region . we designed 290 donor probes on both strands immediately 5 of the 145 bamhi sites in the interval chr9:21035934 - 22494089 ( hg18 ; except where acceptor probes were designed ) . a universal sequence added to the probes is compatible with illumina ga adapters for direct sequencing . the 12 acceptor probes and 290 donor probes ( supplemental table 8) were pooled in equimolar amounts , separately . 3d - dsl sequencing : the dsl ligation products were prepared as described in kwon et al.23 . 3c was performed as per lieberman - aiden et al 28 and the products were sheared by sonication . donor and acceptor probes pools were annealed to the biotinylated 3c samples and the biotinated dna was bound on to streptavidin magnetic beads . the ligated products were washed and eluted from the streptavidin magnetic beads , followed by pcr amplification and deep sequencing on the illumina ga2 ( supplemental information ) .

genome wide association studies ( gwas ) have identified snps in the 9p21 gene desert associated with coronary artery disease ( cad)14 and type 2 diabetes ( t2d)57 . despite evidence for a role of the associated interval in neighboring gene regulation810 , the biological underpinnings of these genetic associations to cad or t2d have not yet been explained . here we identify 33 enhancers in 9p21 ; the interval is the second densest gene - desert for predicted enhancers and 6 times denser than the whole genome ( p<6.55 1033 ) . the cad risk alleles of snps rs10811656/rs10757278 are located in one of these enhancers and disrupt a binding site for stat1 . lymphoblastoid cell lines ( lcl ) homozygous for the cad risk haplotype exhibit no binding of stat1 , and in lcl homozygous for the cad non - risk haplotype binding of stat1 inhibits cdkn2bas expression , which is reversed by sirna knock - down of stat1 . using a new , open - ended approach to detect long - distance interactions ( 3d - dsl ) , we find that in human vascular endothelium cells ( huvec ) the enhancer interval containing the cad locus physically interacts with the cdkn2a / b locus , the mtap gene and an interval downstream of infa21 . in huvec , ifn activation strongly affects the structure of the chromatin and the transcriptional regulation in the 9p21 locus , including stat1 binding , long - range enhancer interactions and altered expression of neighboring genes . our findings establish a link between cad genetic susceptibility and the response to inflammatory signaling in a vascular cell type and thus demonstrate the utility of gwas findings to direct studies to novel genomic loci and biological processes important for disease etiology .

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acute promyelocytic leukemia ( apl ) , m3 subtype of acute myeloid leukemia ( aml ) is characterized in the majority of cases by proliferation of neoplastic hypergranlar promyelocytes and blast . the biological and clinical heterogenicity of apl is based on the clinical presentation of the disease and various characteristics of leukemic cells at diagnosis . patients with apl typically present with low white blood counts , peripheral blood cytopenias and coagulopathy . we report a case of apl- hypogranular variant that poses particular diagnostic challenge because of its atypical morphology . a 30-year - old male presented with severe anemia , bilateral subconjunctival haemorrhage and petechial skin rashes . hematological examination showed a low hemoglobin count ( 9.0 gm% ) , total leucocyte count was markedly raised ( 80,000 cells / cu ) with predominance of promyelocytes and blasts on differential count and platelet count of 34,000 cells / cu . coagulation studies showed prothrombin time ( pt ) to be 15.2 s , activated partial thromboplastin time ( aptt ) 27.5 s and fibrinogen 1.05 peripheral blood cytomorphology showed promyelocytes with a characteristic bilobed or reniform nucleus ; with majority of the cells either devoid of granules or contained only a few fine azurophil granules ( figure 1 ) . the bone marrow aspirate was markedly hypercellular and frankly leukemic , 95% cells were blasts with bilobulated nucleus and fine dust like cytoplasmic granules . molecular cytogenetic analysis by fluorescent in situ hybridization ( fish ) was used to investigate chromosomal abnormalities associated with the leukemic process and found out to be translocation of chromosome 15 and 17 , i.e. , t(15;17 ) ( figure 3 ) . acute promyelocytic leukemia : fish technique shows chromosomal translocation , t(15;17 ) . in view of the atypical blasts morphology , a provisional diagnosis of hypogranular variant of aml - m3v was suggested . the patient was immediately started on all trans - retinoic acid ( atra ) and cytarabine and is progressing well after 12 months of follow up period . this case report emphasizes the importance of a high index of suspicion for the diagnosis of acute promyelocytic leukemia , the hypogranular variant in particular . overall , classical hypergranular and hypogranular variant constitute 58% of cases of aml in different western series , and hypogranular variant comprises 1/3 of all cases of acute promyelocytic leukemia . both apl subtypes share a common pathogenic pathway , namely presence of t(15;17)(q21;q22 ) translocation and a similar clinical picture , namely consumptive coagulopathy at presentation ( table 1 ) . they are responsive to differentiation therapy with all trans - retinoic acid ( atra ) and compete remission in seen in > 80% cases . quite similarly our case is progressing well after 6 months of follow of period . grignani et al . have asserted that fish is rapid and cost - effective when compared to classical cytogenetics , to establish diagnoses for the specific translocation t(15;17 ) in apl patients . proper diagnosis of apl is critical for two reasons : i ) anticipating complications due to disseminated intra - vascular coagulation ( dic ) and ii ) treatment with tretinoin ( all - trans - retinoic - acid ) for complete remission in about 80% of patients . table 1a comparison of classical hypergranular and hypogranular variant.hypergranularhypogranulardefinitionaml subtype in which maturation arrests in promyelocytic stage.clinicaldisseminated intravascular coagulation / consumption coagulopathywbclowhighnucleusround to ovalbilobedcytoplasmdensely packed large azurophilic granules , multiple auer rods , aggot cells.granules apparently absent , typical hypergranular promyelocytes exists in small numbercytochemistrymyeloperoxidase and sudan black - b strongly positiveimmunophenotypecd 33 + , cd 34/+ , cd15/+ ; cd 56/+ ; hla dr positivecd 13 + , cd 34 + , hla dr negativecytogeneticst(15;17 ) ( q22;q12 ) to conclude , the therapeutic option and prognostic implication in apl - variant has made early diagnosis of paramount clinical significance . although , the cytogenetic and immunophenotypic signature should be referred to in diagnosing apl , from the practical point of view , other parameters , such as cytomorphology and cytochemistry are still important tools for rapid recognition of apl .

early diagnosis of acute promyelocytic leukemia ( apl ) is essential because of its associated life threatening coagulopathy and unique response to all trans - retinoic acid ( atra ) therapy . the characteristic cell morphology supplemented by cytochemistry offers the most rapid means for diagnosis . here we describe a rare case of acute promyelocytic leukemia - hypogranular variant that poses particular diagnostic challenge .

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approximately 24 per cent of small bowel obstructions ( sbos ) are caused by bezoars . in addition , presentation with features of acute surgical abdomen is extremely rare , accounting for only 1% of the patients . a bezoar is a concretion of indigestible material found in the gastrointestinal tract , which usually forms in the stomach and passes into the small bowel , where it can cause sbo . it can be classified into one of four major types : trichobezoar , pharmacobezoar , lactobezoar and phytobezoar . trichobezoars are composed of hair and are most commonly associated with patients who have a psychiatric disorder . phytobezoars are composed of undigested fiber from vegetables or fruits and are the most common form of bezoar encountered as a postoperative complication after gastric bypass . a 63-year - old syrian male presented to the emergency department with a 2-day history of generalized colicky abdominal pain associated with repeated vomiting and absolute constipation . there was no associated history of alteration of bowel habit , rectal bleeding , fever or dysuria . his past medical history was significant for a laparotomy in 1979 due to a peptic ulcer - related complication , but he was unaware of the details . he was also recently diagnosed with diabetes mellitus for which he was using herbal treatment consisting of boiled olive tree leaves ( olea europaea ) . on physical examination there was a midline laparotomy scar with a reducible incisional hernia in the epigastric area . he had mild lower abdominal tenderness with no muscle guarding and his bowel sounds were exaggerated . rectal examination revealed no abnormalities and there was a small amount of stool in the rectum . routine blood investigation and abdominal x - rays were obtained . apart from leukocytosis , they were unremarkable . a contrast - enhanced ct scan was arranged and it showed features of sbo with collapse of the terminal ileum . there was evidence of a previous gastrojejunostomy with suspected foreign bodies in the stomach and proximal ileum . ( figs 1 and 2 ) figure 1:contrast - enhanced abdominal ct scan in coronal view showing evidence of gastrojejunostomy and visible foreign body in the stomach and features of small bowel obstruction . figure 2:sagittal ct scan view showing foreign bodies in the stomach and the ileum with transition point in the small bowel .. contrast - enhanced abdominal ct scan in coronal view showing evidence of gastrojejunostomy and visible foreign body in the stomach and features of small bowel obstruction . sagittal ct scan view showing foreign bodies in the stomach and the ileum with transition point in the small bowel . at laparotomy an obstructing hard foreign body was palpable in the ileum with dilatation of the proximal small bowel loops . 3 ) both foreign bodies were removed through an enterotomy and gastrotomy , respectively , and the bowel was decompressed . after limited adhesiolysis , the abdomen was closed en mass repairing the midline hernia defect . figure 3:retrieved phytobezoars . retrieved phytobezoars . postoperative recovery was unremarkable except for a short duration of ileus , after which the patient made a steady recovery . he was referred to the diabetology department and dietician during admission and was discharged with outpatient clinic follow - up . a follow - up upper gi endoscopy was done and it showed evidence of a hiatus hernia with gastrooesophageal reflux disease . the incidence of bezoar formation after gastric surgery ranges from 5 to 12 per cent . the main pathogenesis of bezoar formation is believed to be the result of gastric dysmotility and decreased gastric secretions , which is very common after any gastric surgery [ 3 , 4 ] . diospyrobezoars , formed after persimmon ingestion , are a distinct type of phytobezoars characterized by their hard consistency . coca - cola ingestion combined with endoscopic techniques has been used effectively to treat gastric phytobezoars and avoid surgery . phytobezoar should be considered in patients with previous gastric outlet surgery who present with bowel obstruction and features of acute surgical abdomen . the presence of a well - defined intraluminal mass with a mottled gas pattern on emergency ct scan is suggestive of an intestinal phytobezoar . guidelines include proper chewing of food , plenty of liquids with meals and avoidance of a high - fiber diet .

approximately 24 per cent of small bowel obstructions ( sbo ) are caused by bezoars . in addition , presentation with features of acute surgical abdomen is extremely rare , accounting for only 1% of the patients . a bezoar is a concretion of indigestible material found in the gastrointestinal tract , which usually forms in the stomach and passes into the small bowel , where it can cause sbo . we present the case of a 63-year - old male who presented with sbo following ingestion of boiled olive leaves as herbal treatment for diabetes mellitus .

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darier 's disease is an autosomal dominant disorder of keratinization affecting the skin , mucosa , and nails that typically manifests in the first and second decade of life . we describe an elderly man with nonmetastatic gastric adenocarcinoma presenting with an acquired variant of darier 's disease presumably of paraneoplastic origin . a 62-year - old muslim farmer was in otherwise good health until 2 months back when he suddenly started noticing some dark - colored , mildly itchy skin eruption . he also complained of nausea , vomiting , and loss of appetite and a single episode of passage of black , tarry stool . on examination of his skin , numerous hyperpigmented , warty papules were seen over the face , neck , trunk , and scalp . the lesions were characteristically distributed in seborrheic areas like head neck area , back , and front of chest [ figure 1 ] . there was punctate keratoderma of palms and soles with a few palmar pits as well [ figure 2 ] . v-like notch at the free edge of the nail plate without longitudinal streaks . on the basis of these clinical features , there was neither a past history of similar lesions nor any family history of the same . dirty , warty papules over the back palms showing pits and keratoderma histopathology of the skin lesions revealed suprabasal acantholytic cleft and dyskeratotic cells like corps ronds and grains [ figure 3a and b ] . diminution of lesions following tumor resection ( a ) on back ; ( b ) on chest and palm he was referred to the gastroenterology department where after a series of investigations including endoscopic biopsy , he was diagnosed with gastric adenocarcinoma . on his next follow - up in our outpatient department ( opd ) 2 months later , we discovered that the skin lesions had remarkably diminished [ figure 4a and b ] . by that time it was then that we retrospectively considered darier 's disease to be a paraneoplastic phenomenon . histopathology showing ( a ) prominent hyperkeratosis and suprabasal acantholytic cleft with villi ( h and e , 100 ) ; ( b ) dyskeratotic cells ( h and e , 400 ) paraneoplastic dermatoses describes those benign skin changes in which there is a direct , often parallel course of a dermatosis with an underlying malignancy . there are several proposed hypotheses on the pathomechanism of paraneoplastic dermatoses , which highlight the role of various tumor - derived growth factors like transforming growth factor ( tgf- ) , fibroblast growth factor , and so on . regarding the pathogenesis of paraneoplastic darier 's disease , it can be speculated that the tumor product interferes with keratinocyte calcium homeostasis leading to disturbances in intracellular trafficking of desmosomal proteins . the autosomal dominant variety is due to mutations in the serca2 ( sarco / endoplasmic reticulum calcium atpase type 2 ) , which regulates calcium homoestasis in the endoplasmic reticulum . our case involves an acquired form of darier 's disease whose diagnosis was supported both clinically and histopathologically . although there are several variants of darier 's disease , the paraneoplastic variety is extremely rare . there is only a single case report on its association with metastatic papillary carcinoma of thyroid . there are some sporadic reports on the occurrence of squamous cell carcinoma of skin , nail bed , esophagus , mouth , and vagina in patients with pre - existing darier 's disease but paraneoplastic association is very rare . according to the criteria proposed by helen ollendorff curth , a specific dermatosis occurs with a specific neoplasm , and a high percentage of association between two conditions is noted . this does not hold true in our case . the paraneoplastic dermatoses that have been reportedly associated with gastric adenocarcinoma are acanthosis nigricans , tripe palms , and florid cutaneous papillomatoses . we consider this a paraneoplastic process due to its concurrent onset and almost parallel course with malignant neoplasm , which are also important requisites in the curth criteria . moreover , in this case , onset of darier 's disease was late , occurring in the seventh decade of life in contrast to its usual onset in the second decade of life . also the skin changes resolved with treatment of the underlying cancer . this further served as an eye - opener for the clinical investigators of this case . its paraneoplastic association with gastric adenocarcinoma is very unusual and not known to be mentioned in any dermatology literature so far and hence reported here . darier 's disease is an unusual paraneoplastic manifestation in gastric malignancy , not reported before .

darier 's disease is an autosomal dominant genodermatosis resulting from atp2a2 gene mutation . a 62-year - old male presented at our outpatient ( opd ) with sudden - onset numerous dirty , warty papules over the head , neck , and back since 2 months . histopathology of the skin lesions revealed acantholytic dyskeratosis suggestive of darier 's disease . he was referred to the gastroenterology department for some gastrointestinal ( gi ) symptoms where he was diagnosed with adenocarcinoma of the stomach and was subsequently operated . on his next visit to our department for follow - up , we found a marked diminution of the skin lesions in the absence of any specific treatment . in view of the above finding , we concluded that paraneoplastic dermatosis in the form of darier 's disease occurred in this patient . paraneoplastic darier 's disease with gastric adenocarcinoma is not yet described in dermatology literature and is hence reported here .

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recently , serratia , pseudomonas / providencia , indole - positive proteus / acinetobacter / morganella , citrobacter , enterobacter and hafnia group of organisms ( spice ) were described to cause peritoneal dialysis ( pd)-related peritonitis with a particularly high morbidity and mortality . peritonitis caused by citrobacter is relatively uncommon and citrobacter freundii is the most common species involved . we report a case of pd - related peritonitis caused by c. freundii , which was successfully treated with double antibiotic coverage . a 76-year - old male with end stage renal disease due to type ii diabetes mellitus on pd for 6 months presented to the emergency room with abdominal pain and bloody peritoneal dialysate for 1 day . he was on regular maintenance automated pd using a cycler and reported no history of breakdown of aseptic technique or contamination during the catheter care . upon examination , he was hypotensive with a blood pressure of 98/54 mm hg but afebrile and the catheter exit site was benign . a dialysate cell count and culture was obtained and the patient was started on empirical intravenous broad - spectrum antibiotic coverage with vancomycin and aztreonam ( he was allergic to penicillin ) . pd was continued during the hospital stay with the addition of 500 units of unfractionated heparin per liter of dialysate . his dialysate white blood cell count was > 3700 with 92% neutrophils and c. freundii was isolated upon its culture . a computed tomography scan of the abdomen showed no evidence of intestinal perforation , appendicitis or diverticulitis . subsequently , his clinical condition stabilized with subsiding abdominal pain clearing of dialysate in 2 days . his antibiotic coverage was switched to oral ciprofloxacin along with intraperitoneal gentamycin , requiring an additional daytime manual exchange with 6-h dwell time in order to provide sustained antibiotic exposure to the infected peritoneal membrane , which is not possible with the cycler - assisted pd exchanges . the antibiotics were continued for a total duration of 14 days , and he was discharged in a stable condition . peritonitis caused by the members of the family enterobacteriaceae is an important cause of mortality and morbidity in pd patients and accounts for up to 12% of all peritonitis episodes in some series . citrobacter species , a part of this family , were not commonly associated with peritonitis until recently , when they were described among the spice organisms causing severe peritonitis . most commonly , c. freundii has been associated with urinary tract infections , superficial wound infections and bacteremia especially in elderly , immunocompromised and hospitalized patients . it colonizes the gastrointestinal tract of humans and other animals and its translocation to the blood stream in dialysis patients especially in the setting of abnormal bowel habits is implicated in the development of peritonitis . our patient had a particularly severe peritonitis with hemodynamic instability , and prompt use of intravenous broad spectrum antibiotics was life - saving . we encountered a bacterial strain that was resistant to ampicillin ; a commonly described property of c. freundii and ascribed to the ampc gene , which provides high - level resistance to ampicillin and first generation cephalosporins . indeed , the last published guidelines of the international society of pd in 2010 recommend following the sensitivity patterns in case of spice organisms and consider using double antibiotic coverage for 23 weeks . earlier literature reports a high incidence of mortality and morbidity from catheter losses from pd - related peritonitis caused by c. freundii . prompt institution of broad antimicrobial coverage in unstable patients and following the culture sensitivity pattern reduces mortality and catheter losses from peritonitis caused by c. freundii .

serratia , pseudomonas / providencia , indole - positive proteus / acinetobacter / morganella , citrobacter , enterobacter and hafnia group of organisms cause peritoneal dialysis ( pd)-related peritonitis with high morbidity and mortality . peritonitis caused by citrobacter freundii is uncommon , and it may lead to catheter removal despite antimicrobial treatment . we describe a case of pd - related peritonitis caused by c. freundii , which was successfully treated with double antibiotic coverage .

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sepsis has been classically considered the archetypal clinical condition with molecular links between inflammation and coagulation . both inflammation and thrombosis can be orchestrated by the interactions between circulating cells , such as lymphocytes , platelets , and vascular cells , which under activation or apoptosis lead to the release of circulating microparticles ( mps ) . in the previous issue of critical care , prez - casal and colleagues hypothesized that circulating mps may retain their anti - inflammatory and cytoprotective properties in septic patients during recombinant human activated protein c ( rhapc ) infusion in vivo and probably participate in its clinical benefit . the same group has previously shown that activated protein c ( apc ) can generate mps in vitro from endothelial cell protein c receptor ( epcr)-expressing cells , which retain anticoagulant and protease - activated receptor-1 ( par-1)-dependent anti - inflammatory properties . apc binding to epcr at the endothelial cell surface and apc on mp - epcr could cleave and activate par-1 , sphingosine 1-phosphate receptor and kinase insert domain receptor . rhapc treatment for severe sepsis can induce the generation and release of mps in vivo , with a clinical correlative trend towards improved outcome . circulating mps from patients during rhapc treatment express apc , epcr and cd13 . these mps interact with endothelial cells and induce changes in gene expression to inhibit apoptosis and reduce endothelial permeability . these effects require par-1 activation by apc in an epcr - bound conformation , confirming the evidence for the assembled epcr - apc complex on in vivo - derived mps . the present work suggests that mps could disseminate apc function and activate endothelial par-1 at distal vascular sites . the mps represent an additional circulatory form of apc receptor in human plasma , which is different from soluble epcr . mp - associated apc is stable in measurable levels , and activities would point to physiological and clinical relevance as bioactive effectors in rhapc - treated patients and contribute to the effectiveness of rhapc in severe sepsis the authors did not analyze the subpopulation of cd13 mps upon rhapc treatment , whether they are from endothelial or leukocyte origins . indeed , they have shown that apc induces mp - associated epcr formation from monocytes and human endothelial cells . furthermore , whether such mps contribute to the ability of rhapc treatment to improve cardiovascular function - including arterial contractility and endothelial dysfunction by decreasing tissue inflammation and oxidative stress as reported in an experimental model of sepsis - remains to be determined . a fragile balance between the harmful and helpful effects of mps especially during severe sepsis should be underlined . circulating mps from septic patients might exert a protective role at the vascular level by compensating hyporeactivity , but they might also contribute to the cause of multiorgan failure in sepsis and induce deleterious protein changes in target tissues . it would be of interest to test the hypothesis that rhapc via increased certain subtypes of mps bearing epcr / apc would contribute to the correction of multiple organ failure , which would lead to increased survival . the clinical relevance of rhapc treatment via increased apc / epcr - mps requires further exploration , especially in larger numbers of patients with septic shock and higher mortality . in conclusion mps could potentially be developed as new therapeutic tools to transfer biological vectors of cellular communication and are able to modulate important cellular regulatory functions at a distal site of its production in response to pharmacological agents such as rhapc . apc : activated protein c ; epcr : endothelial protein c receptor ; mp : microparticle ; par-1 : protease - activated receptor-1 ; rhapc : recombinant human apc .

activated protein c ( apc ) , a physiological coagulation inhibitor , has been shown to reduce mortality in patients with severe sepsis . apc exerts pleiotropic cytoprotection by a mechanism that requires its interaction with endothelial cell protein c receptor and protease - activated receptor-1 on target cells . in the previous issue , prez - casal and colleagues elegantly demonstrate that apc , using its recombinant form ( rhapc ) , can communicate to target cells through release of microparticles ( mps ) , small membrane vesicles released from activated cells , to induce anti - apoptotic and anti - inflammatory properties that might participate in the improvement of patient outcome . of interest is the fact that apc itself promotes the release of mps from target cells including endothelial cells and monocytes . these mps bear the endothelial cell protein c receptor / apc molecules and can transfer the message to target cells including those of origin to induce cytoprotection . the long - range apc signal can thus be mediated by mps in vivo upon pharmacological treatment using rhapc in severe septic patients . a novel pharmacological approach targeting mp production and properties could therefore be used to treat severe sepsis in addition to other well - known actions of apc via direct interaction with the cells of interest .

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diastolic mitral regurgitation has been described in patients with acute aortic regurgitation and those with atrioventricular block or atrial fibrillation with slow ventricular responses . evidence of diastolic mitral regurgitation in these patients has been demonstrated previously by left ventriculography and recently by pulse doppler echocardiography . the mechanisms of diastolic mitral regurgitation in patients with acute aortic regurgitation have been considered to be the summation of the following pathophysiology : reversed atrio - ventricular pressure gradient due to aortic regurgitation in the non - compliant ventricle , increased mitral annulus due to ventricular relaxation and lack of papillary muscle tension . that of the patients with atrioventricular block or atrial fibrillation has been considered to be lack of atrial factors for mitral valve closure . we documented diastolic mitral regurgitation by color doppler echocardiography in a patient with acute aortic regurgitation . color doppler flow imaging is highly useful in detecting valvular regurgitation , especially in determining flow direction . therefore , this technique may provide additional information regarding the mechanism by which diastolic mitral regurgitation is produced . reversibility of diastolic mitral regurgitation after correction of hemodynamic loading , that was widely believed but not actually demonstrated , was also observed . a 38-year - old japanese man with no previous cardiovascular disease was admitted to our hospital because of paroxysmal nocturnal dyspnea and low grade fever of four weeks duration . he had the history of the resection of subcutaneous abscess in the neck , several days before the onset of symptom . on admission , an early systolic murmur and a diastolic blowing murmur with thrill were detected at the left parasternal border . increased pulmonary vascular marking was observed in his chest x - ray and the cardio - thoracic ratio was 50% . electrocardiogram revealed a prolonged p - q interval of 0.28 second , left ventricular hypertrophy and st depression in the left precordial leads . after admission , first - degree of atrioventricular block normalized in 0.18 second of p - q interval . echocardiography was performed with a tohshiba 65a after normalization of p - q interval , which revealed the dilated and hyperkinetic left ventricle and the slightly dilated left atrium . 1 ) , and the left ventricular end diastolic dimension was 6.4 cm and the end systolic dimension was 4.4 cm . the right coronary cusp and left coronary cusp of the aortic valve were extremely elongated and the left valsalva sinus was dilated . both aortic cusps were prolapsing and no coaptation was seen . severe aortic regurgitation was observed on color doppler flow imaging . in late diastole , mitral regurgitation which ran just behind the posterior mitral leaflet and extended to the posterior wall of the left atrium was detected ( fig . the diastolic mitral regurgitation began with the atrial systole and disappeared with the ventricular systole ( fig . although several blood cultures were all negative , the diagnosis of acute aortic regurgitation due to infective endocarditis was made from the clinical history and destructive changes of the aortic valve . after intensive antibiotic therapy for three weeks , aortic valve replacement was performed . at surgery , commissural rupture between the right coronary cusp and the left coronary cusp was detected and an abscess was present in the root of the left coronary cusp . diastolic mitral regurgitation in patients with acute aortic reguritation in patients with acute aortic regurgitation is considered to be produced by hemodynamic abnormalities , not by intrinsic abnormalities of mitral leaflets . however , the proof of this consideration is somewhat obscure . in most reported cases with diastolic mitral regurgitation , the concurrent presence of systolic mitral regurgitation , which indicates the presence of intrinsic abnormalities of mitral leaflets or apparatus , was reported . if the mitral valve is truly normal , systolic mitral regurgitation should be absent and diastolic mitral regurgitation should disappear with resolution of the hemodynamic abnormalities . the reversibility of diastolic mitral regurgitation after aortic valve replacement has never been described . in this case , the mitral regurgitation was observed only in the period of late diastole , disappearing with the ventricular systole . furthermore , the diastolic mitral regurgitation in this case could not be detected after the successful aortic valve replacement . our case clearly indicates that acute aortic regurgitation can produce diastolic mitral regurgitation in a normal mitral valve . in this case , the flow of the diastolic mitral regurgitation was directed to the posterior wall of the left atrium through just behind the posterior mitral leaflet . from above mentioned mechanisms of diastolic mitral regurgitation in acute aortic regurgitation , if intrinsic abnormalities of the mitral leaflets are absent , regurgitant flow should be directed to the center of the left atrium . extreme deviation of mitral regurgitant flow is observed in cases of mitral valve prolapse or those with severely restricted mitral valve leaflets , as is seen in rheumatic mitral disease . because this case showed no abnormalities in the mitral leaflets under echocardiography , severely restricted movement of the mitral leaflets is unlikely . we speculated either that the aortic regurgitant jet might depress the anterior mitral leaflet toward the left atrium or that acute left ventricular enlargement due to aortic regurgitation might retract the chordae connecting to the posterior mitral leaflet . these processes would result in the dislodgment of the tips of both leaflets , creating extreme deviation of the mitral regurgitant flow similar to mitral prolapse . there are a few reports on the observation of diastolic mitral regurgitation by color doppler echocardiography , but no comments for the flow direction . this case indicated the possibility of additional mechanisms of diastolic mitral regurgitation , namely , depression of the anterior mitral leaflet or retraction of the chordae connecting to the posterior mitral leaflet .

a 38-year - old man was admitted with coingestive heart failure due to infective endocarditis . echocardiography with color doppler imaging revealed severe aortic regurgitation , mitral valve premature closure and diastolic mitral regurgitation . the flow of the diastolic mitral regurgitation was directed to the posterior wall of the left atrium through just behind the posterior mitral leaflet . the diastolic mitral regurgitation was observed only in the period of late diastole and no mitral regurgitation could be detected in the systolic phase . after successful aortic valve replacement , the diastolic mitral regurgitation disappeared completely .

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brucellosis ( malta fever ) is an infectious disease with a wide range of manifestations . there are four types of brucella , b. melitensis , b. abortus , b. canis and b. suis . bacteria are transmitted to humans via the injection of non - pasteurized dairy products , uncooked raw meat or by contact through skin , blood , conjunctiva , gastrointestinal or respiratory tracts.12 although the incidence of brucellosis has declined , it is still remains an important health problem in endemic areas such as the middle east , the mediterranean and asia . iran is considered an endemic country as are peru , saudi arabia , kuwait and turkey.34 according to the report of the diseases prevention and fight department of iran s health center , published in 2009 , the incidence of brucellosis was 25 in 100,000 people . in hamadan , studies show that b. melitensis is the most common and virulent species with a high prevalence in latin america , mediterranean and developing countries . b. abortus is reported mostly in europe and north america . despite the decrease in total prevalence of the disease a 29-year - old male was referred to infectious disease clinic of hamadan sina hospital in summer 2008 with acute onset of fever , headache , malaise , sweating and low back pain . on examination laboratory test findings were : white blood cell ( wbc ) count of 13350 ( neutrophil : 85% ) , erythrocyte sedimentation rate ( esr ) 48m / h , crp , rf , ana , wright s agglutination titer of 1/1280 . blood cultures were negative and electrocardiogram and chest - x - ray ( cxr ) were normal . the patient was diagnosed with brucellosis , and treated with rifampin 600 mg / day and doxycycline 100 mg / twice daily . after a week , the patient was referred for an ophthalmology consult with complaints of ocular pain and redness and visual complaints . on ophthalmic examination , the conjunctional injection was a mixture of ciliary injection , episcleritis and conjunctivitis but more severe in the ciliary area . on funduscopy , there was bilateral optic disc swelling along with retinal hyperemia ( optic disc hyperemia and vascular tortuosity ) and diffuse intraretinal hemorrhage [ figure 1 ] . intraocular pressure ( iop ) was 26 mmhg in the right eye and 24 mmhg in the left eye . the patient was hospitalized with a probable diagnosis of ocular brucellosis and was treated with co - trimoxazole adult two tablets , three times a day ( tid ) , rifampin 600 mg / day doxycycline 100 mg / bid and prednisolone 1 mg / kg for 2 months . computed tomography and magnetic resonance imaging studies of the brain and optic nerve were requested . fever and headache diminished within 48 hours of the treatment however , ophthalmic complaints lingered . bilateral optic disc swelling with retinal hyperemia ( optic disc hyperemia and vascular tortuosity ) and diffuse intraretinal hemorrhage fundoscopic findings 13 months after treatment for brucellosis brucellosis presents with a spectrum of clinical manifestations and diagnosis of this disease is based on clinical signs , positive bacteriological and serological tests . some ocular manifestations including dacryoadenitis , episcleritis , chronic iridoscleritis , nummular keratitis , cataract , glaucoma , multifocal choroiditis , exudative retinal detachment , maculopathy , and optic neuritis.814 rolando et al.14 showed that the most frequent ocular manifestation is uveitis predominantly posterior uveitis . it seems that optic nerve involvement is secondary to meningeal inflammation and flow change of the optic nerve due to axonal degeneration.14 visual improvement of the patient following corticosteroid administration is proof of ischemic or vasculitic involvement.1410 ophthalmic manifestations of brucellosis are not common and acceptable outcomes following treatment with antibiotics and steroids are low.9101517 cavallarro et al.18 reported a patient with papilledema due to brucellosis that was treated with sole anti - brucellosis treatment without steroid administration . abd - elrazak19 reported a case of bilateral optic neuritis caused by brucellosis that resolved following anti - brucellosis and steroid administration . lashay et al.20 from iran reported a case of bilateral optic nerve head swelling following brucellosis , which led to bilateral optic nerve atrophy and visual loss . in our case , antibiotic and steroid administration led to complete visual recovery and in 13 months follow - up after treatment , ophthalmologic examinations were normal . the outcome in our case is likely due to early diagnosis and treatment , lack of a drug resistant strain and better prognosis in males compared to females.142123 in the current case , imaging studies were normal . however , such lesions may be missed on routine imaging studies if magnetic resonance angiography ( mra ) is not performed . considering the rapid response to the therapeutic interventions likewise , other possible causes of conjunctival injection associated with increased venous pressure such as cavernous sinus thrombosis or orbital apex syndromes were ruled out due to this quick and appropriate response to treatment . the prevalence of brucellosis has decreased in many developed countries and ophthalmic complications are rare in these regions , but it is suggested that in endemic areas , routine ophthalmic examination for brucellosis be considered , as it seems that early diagnosis and prompt treatment of the disease could decrease vision - threatening complications.23

a 29-year - old male diagnosed with brucellosis a week earlier was referred to the ophthalmology clinic with visual complaints . on examination , visual acuity was 20/25 , he had conjunctival injection on slit lamp examination . there was also bilateral optic disk swelling plus retinal hyperemia ( optic disc hyperemia and vascular tortuosity ) and intraretinal hemorrhage on funduscopy . the patient was admitted and treated with cotrimoxazole , rifampin , doxycycline and prednisolone for 2 months . ocular manifestations subsided gradually within 6 months after treatment . brucellosis can affect the eye and lead to serious ocular complications . early diagnosis and prompt treatment should be considered in endemic areas .

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linear and whorled nevoid hypermelanosis ( lwnh ) is a rare sporadic pigmentary anomaly , characterized by swirls and streaks of macular hyperpigmentation following the lines of blaschko , without preceding inflammation , and is usually seen in the first 2 years of life . include zosteriform hyperpigmentation , zosteriform lentiginous nevus , zebra - like hyperpigmentation , reticulate hyperpigmentation of iijima , and nevoid hyperpigmentation following blaschko lines . a 22-year - old male presented to the outpatient department with chief complaints of asymptomatic , dark - colored skin lesions over the body since 10 years of age . according to the patient , the lesions first appeared over both his arms and progressed within the next 2 years to involve the trunk and lower limbs . the lesions darkened with age and no new lesions appeared over the next 9 years ; however , over the last 1 year he started noticing multiple white - colored , pinpoint lesions appearing over the hyperpigmented lesions without any preceding skin itching or redness . there was no history of warty lesions or blisters prior to the appearance of these lesions . there was no history suggestive of any recurrent lower respiratory infections or involvement of the cardiovascular and the central nervous systems . the patient described presence of similar dark - colored skin lesions involving the trunk , arms , and legs in his mother without a history of any light - colored patches . cutaneous examination revealed presence of multiple , whorled , hyperpigmented macules , arranged bilaterally and symmetrically , along the lines of blaschko on the abdomen , chest , and back [ figure 1 ] . similar lesions were arranged linearly on the extensor and flexor aspects of the arms and legs . multiple pinpoint depigmented macules were seen along the areas of streaky macular pigmentation [ figure 1 ] . the texture of skin was normal over the streaks , the intervening skin , and over the depigmented areas . classical whorled , hyperpigmented macules along the lines of blaschko on the trunk with pinpoint areas of depigmentation hematological and routine biochemical tests revealed no abnormalities . histopathological evaluation of the depigmented lesion showed complete absence of melanocytes [ figure 2a ] . however , the pigmented macules revealed increased pigmentation of the basal cell layer with melanocytes present up to the mid - epidermis [ figure 2b ] . no focal areas of pigmentary incontinence were noticed in the dermis . based on clinicopathological correlation , a diagnosis of lwnh with punctate hypopigmentation was made . however , treatment for depigmented areas with narrow band ultraviolet b radiation and topical corticosteroids was advised . picture collage showing histopathological examination ( a ) complete absence of melanocytes in the depigmented area ( b ) abundance of melanocytes in the hyperpigmented area ( h and e , 40 ) linear and whorled nevoid hypermelanosis is a rare disorder of pigmentation characterized by hyperpigmented macules in a linear or whorled streaky configuration . onset is within a few weeks of age , with no preceding inflammation or palpable lesion . the usual age of the onset of hyperpigmentation is within the first few weeks of life , which continues to progress for a year or two before stabilization . clinically , reticulate hyperpigmented macules coalescing to form streaks and whorled areas are seen over the trunk , extremities , and neck following the lines of blaschko . the pigmented streaks display a v - shaped pattern over the spine , an s - shaped or whorled pattern over the anterior and lateral aspects of the trunk , and a linear arrangement over the extremities and genitalia . there is sparing of the face , palms and soles , eyes , and mucous membranes . central nervous system diseases include microcephaly , arhinencephaly and epilepsy whereas cardiac defects include ventricular septal defect and tetralogy of fallot . developmental retardation , facial and body asymmetry , deafness , and brachydactyly have been mentioned in the literature in association with lwnh . histopathology reveals diffuse moderate hyperpigmentation in the basal layer and prominence or vacuolization of melanocytes . genetic studies suggest somatic mosaicism as a cause for lwnh with mosaic trisomy of 7 , 14 , 18 , 20 ; x - chromosomal mosaicism has been reported . dermatoscopic feature mentioned include net like pattern of pigmentation in both linear and whorled parts by naveen et al . , and ertam et al . described a parallel pattern which consisted of linear or circular arrangement of parallel whorled streaks along lines of blaschko . monogenic skin disorders are the ones commonly described with lines of blaschko , however , polygenetic skin disorders such as psoriasis , lichen planus , segmental vitiligo , granuloma annulare , etc . can also present in similar patterns . literature search reveals an entity called as blaschkolinear vitiligo , which has been described in association with segmental vitiligo , acrofacial vitiligo , and non - segmental vitiligo . kovacevic et al . have reported a new entity called as mixed vitiligo of blaschko lines , where they discussed presence of segmental and non - segmental vitiligo in blaschkolinear pattern . till date , no cases of lwnh with areas of depigmentation have been mentioned in the literature , and to the best of our knowledge , this is most probably the first case report of familial lwnh superimposed by pinpoint spots of depigmentation .

linear and whorled nevoid hypermelanosis ( lwnh ) is a rare disorder of pigmentation characterized by hyperpigmented macules in a linear or whorled streaky configuration . lesions are distributed mainly on the trunk and extremities , sparing the palms , soles , and mucosae . depigmentation occurring in the pre - existing whorls has not been reported till date . herein , we report one such rare case of familial lwnh with depigmentation .

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a 12-year - old female patient visited the department of oral medicine and radiology , yenepoya dental college , with a complaint of missing anterior teeth since three years ago . she had a history of exfoliation of decidious teeth due to mobility three years ago and there was no eruption of the permanent teeth . there was a history of presence of two mandibular natal teeth which were exfoliated two weeks after birth . her parents had no consanguineous marriage , however her elder sibling died of similar medical problem . her medical history revealed that she had visited genetic clinic and they have diagnosed her with ellis - van creveld syndrome . she also had dyspnoea because of congenital lobar emphysema for which she had undergone left upper lobectomy when she was one and half year old . intraoral examination showed v - shaped notching of the upper lip at the mid line ( fig . 2a ) , absence of mucobuccal fold in maxillary and mandibular anterior region ( figs . 2b and c ) , conical shaped teeth , missing mandibular permanent anterior and retained deciduous mandibular canines , and right lateral incisor teeth ( fig . 2c ) . chest radiograph showed homogenous opacity in the left upper zone associated with elevation of hilum and left dome of diaphragm suggestive of left upper lobectomy ( fig . antero - posterior view of the legs showed genu valgum , hypoplasia of lateral end of tibia associated with medial tibial diaphysial outgrowth called exostosis , and mild shortening of fibula ( fig . hand - wrist radiograph showed carpal fusion , postaxial polydactyly , and shortening of metacarpal and phalangeal bone with cone shaped epiphysis . there was fusion of capitate and hamate on the right hand and hamate and triquadral on the left hand ( fig . a team work of pedodontist , oral and maxillofacial surgeon , and prosthodontist was required to correct the craniofacial and dental defects in this patient . since the patient was in growing phase , the prosthodontist decided to give acrylic partial dentures for the missing teeth . oral and maxillofacial surgeon performed frenectomy for the high labial frenum as it was hindering the placement of the partial denture . ellis - van creveld syndrome ( evc ) otherwise known as chondroectodermal dysplasia has autosomal recessive inheritance . it is a syndrome found in amish population of pennsylvania in usa , affecting male and female equally.2 familial history may include parental consanguinity or affected siblings or family members . our patient was the second child of non - consanguineous and normally developed parents , however her elder sibling had died of similar medical problem . these patients die due to either cardiac problem or respiratory distress.2 our case did not have any cardiac problem , however there was congenital lobar emphysema because of her dyspnoea . she had undergone left upper lobectomy for the same reason when she was one and half year old child . the syndrome affects mainly the bones such as the lower limb with genu valgum , which requires surgical correction . the upper limbs show the characteristic bilateral postaxial polydactyly.3,4 our case had all these limb anomalies . other ectodermal features in this syndrome are the absence or hypoplastic features of finger and toe nails , natal teeth , conical shaped or missing teeth , and absence of labial vestibule because of fusion of upper lip to the gingival margin , leading to the notching of upper lip . this could be due to the continuation of the normal serrated condition of the gingiva from the third to seventh month in the uterine life of the fetus . it is considered as the characteristic and diagnostic feature of this syndrome.5 - 7 all of these features were also present in this case . there are about 40 independent evc / evc2 mutations.8 ruiz - perez and goodship mentioned that the abnormalities in evc syndrome resulted from the tissue specific disruption of the response to hh ligands.9 weyer 's syndrome , asphyxiating thoracic dystrophy , and orofacial digital syndrome should be considered in the differential diagnosis of this syndrome . evc syndrome and weyer 's acrodental dysastosis are allelic conditions caused by loss of function mutation in evc and evc2 . these are separated by 2 - 6 kb of genomeric sequence on chromosome 4p16.10 all the features are similar in both conditions except for the fact that there is delay in fusion of mandibular symphysis in acrodental dysastosis.6 patients with evc syndrome and asphyxiating thoracic dystrophy will have identical features in hand , pelvis , and long bones . presence of cardiac anomalies , nail hypoplasia , fusion of upper lip to gingiva and neonatal teeth in evc syndrome , and renal failure with hypertension in asphyxiating thoracic dystrophy will help in distinguishing these two disorders from each other.6,11 presence of multiple gingivolabial frenula is similar to evc in orofacial digital syndrome . hypoplastic nasal cartilage , moderate mental retardation , fissured tongue , and ankyloglossia helps to differentiate this from evc syndrome.11 in conclusion , the effective management of this syndrome will require a team which includes pedodontist , oral and maxillofacial surgeon , prosthodontist , clinical geneticist , cardiologist , pulmonologist , orthopaedician , urologist , psychologist , pediatrician , and pediatric neurologist . since the oral manifestation is one of the characteristic diagnostic features , and it affects the esthetic problem , speech , jaw growth of the child , the dentists have an important role to play in proper management of such cases .

ellis - van creveld syndrome is a rare congenital genetic disorder having autosomal recessive inheritance . it is a syndrome affecting the amish population of pennsylvania in usa with prevalence rate of 1/5,000 live at birth . in non - amish population , the birth prevalence is 7/1,000,000 . the syndrome is characterized by bilateral postaxial polydactyly of the hands , chondrodysplasia of long bones resulting in acromesomelic dwarfism , ectodermal dysplasia affecting nails as well as teeth and congenital heart malformation . there were very rare reports of this syndrome in dentistry . the present case focuses on the striking and constant oral findings of these patients , which are the main diagnostic features of this syndrome . since the oral manifestations affect the esthetic , speech , and jaw growth of the child , the dentists have an important role to play in proper management of such case .

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most reported cases have documented the development of significant complications , since it is difficult to diagnose this rare entity preoperatively . the literature is reviewed and the radiologic findings and management of this rare entity are discussed . a 90-year - old woman was referred to our hospital for acute appendicitis complicated with right incarcerated groin hernia . she initially presented to a local hospital with right lower quadrant abdominal pain for one day . the abdomen and pelvic ct with intravenous and oral contrast showed swelling of the appendix with perifocal fat stranding and cecal wall thickening ( figure 1a ) . there was initial improvement , however , a painful and irreducible lump in the right groin developed three days thereafter . on referral , a previously performed ct revealed the finding of a fluid - contained mass with stranding of surrounding fat in the right groin lateral and inferior to the pubic tubercle . neither the appendix nor cecum was in close proximity to the mass ( figure 1b ) . the appendix was inflamed and severely adherent to the cecum and terminal ileum but there was neither perforation nor abscess . the femoral hernia neck was constricted , and there was no herniation of the abdominal viscera ( figure 2a ) . a separate groin incision was made , and phlegmonous inflammation of the distended femoral hernia sac was found ( figure 2b ) . dissection was carried out to free the entire circumference of the hernia sac and the neck . the hernia sac was excised , and the neck was closed with suture - ligation . mcvay hernioplasty was performed . on opening , the sole content of the hernia sac was pus . the reported incidence of appendicitis within a groin hernia is 0.13% of all cases of acute appendicitis.1 it most frequently occurs in the right inguinal and right femoral hernias . rene jacques croissant de garengeot , in 1731 , first reported a case of acute appendicitis within a femoral hernia.2 since then , there have been only scattered case reports of appendicitis within femoral hernias . the clinical presentation usually suggests an incarcerated or strangulated femoral hernia , and acute appendicitis is incidentally found at operation . with the increased use of ct for evaluating patient with atypical presentation of incarcerated hernia and lower abdomen peritonitis , there have been occasional reports in which the diagnosis of hernial appendicitis is made preoperatively . the typical ct features include a tubular structure within the hernia sac with surrounding fat stranding and low position of the cecum or close proximity to the hernia sac.35 this prospective ct diagnosis may be helpful in establishing appropriate treatment strategy . our case illustrates a very rare variety of femoral hernia appendicitis . the appendix was not contained in the hernia sac . instead zuckerkandl first described this phenomenon in 1891 , albeit within an inguinal hernia sac.6 as with any peritoneal recess , the hernia sac may contain pus secondary to any intraperitoneal infectious process . the pus causes distention and inflammation of the sac , which was mistaken for strangulated hernia . the appendix may be either in close proximity to or distant from the hernia sac . there is usually no evidence of intestinal obstruction , which will raise suspicion of strangulated omentum or richter s hernia . once the diagnosis of strangulated femoral hernia is made , most surgeons prefer direct surgical intervention to avoid considerable risk of postoperative complications . thus , the diagnosis of appendiceal pus - containing femoral hernia is made only during the operation . despite wide availability of ct , the ct features of pus - containing femoral hernia is almost never reported in the literature . in our patient , the ct showed an inflammatory fluid - filled mass lateral and inferior to the pubic tubercle , a typical location of acute appendicitis , and no evidence of intestinal obstruction . the differential diagnosis is acute appendicitis complicated with a rare complication of pus - filled femoral hernia or a richter s hernia . as illustrated in our case , the awareness of the ct findings facilitated the decision on a treatment strategy . although drainage of purulent content or appendectomy via hernia sac has been reported in many cases in which diagnosis is not expected , it carries a high rate of infectious complications . separate laparotomy and groin incision would be very helpful in complete dissection and direct excision of the hernia sac . there are some controversies surrounding the method of femoral hernia repair in cases of hernial appendicitis or pus - containing femoral hernia . however , if no spillage of infectious content occurs , mesh repair is a reasonable alternative . in conclusion , selective use of ct for evaluating an atypical case of incarcerated femoral hernia may be helpful in early diagnosis and decision on the treatment strategy . the ct features of typical acute appendicitis and incarceration of inflammatory fluid - filled hernia sac without evidence of intestinal obstruction should raise suspicion of this rare entity .

acute appendicitis involving the hernia sac is infrequent but well - documented in medical literature . in most instances , it occurs within the right inguinal ( amyand s hernia ) or right femoral hernia ( de garengeot hernia ) . the diagnosis is always mistaken for incarcerated groin hernia . during surgery , the appendix itself , either perforated or strangulated , is most commonly encountered within the hernia sac . in very rare occasions , only appendiceal pus is found in the hernia sac . in this paper , we report the case of a 90-year - old woman with acute appendicitis and a tender mass in the right groin . typical findings of acute appendicitis by computed tomography ( ct ) and incarcerated femoral hernia with groin cellulitis misled us into preoperative diagnosis of strangulated femoral hernia . acute phlegmonous inflammation of the incarcerated femoral hernia sac containing pus only and acute suppurative appendicitis were found intraoperatively . this case presents a rare complication of acute appendicitis and the first report of ct - documented appendiceal pus - contained femoral hernia . knowledge of this rare condition is helpful in establishing preoperative diagnosis and patient management decisions .

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e. coli cultures were grown in lb liquid media or on lb agar plates with antibiotics when necessary ( 50 g / ml kanamycin , 50 g / ml apramycin , 25 to 50 g / ml chloramphenicol , 50 g / ml carbenicillin ) at 37 c with shaking . streptomyces liquid precultures were grown in tryptic soy broth with the appropriate antibiotics ( 50 g / ml kanamycin , 50 g / ml apramycin , 25 g / ml nalidixic acid ) , inoculated into ssm media ( 1% soytone , 1% soluble starch , 2% maltose , 0.5% trace element solution , ph 5.7 ) and grown at 30 c with shaking . streptomyces were also grown on mannitol soya flour medium plates ( 2.0% agar , 2.0% mannitol , 2.0% soya flour ) with appropriate antibiotics ( 50 g / ml kanamycin , 50 g / ml apramycin , 25 g / ml nalidixic acid ) . salinispora were grown in a1 media ( 1.0% starch , 0.4% yeast extract , 0.2% peptone , and 2.8% sea salt ) at 30 c with shaking . the method of tar capturing used in this study has been previously reported . the isolation of high - quality genomic dna from salinispora was performed according to standard procedures . the capture vector , pcap01 , containing yeast arsh4/cen6 and trp1 marker , e. coli puc ori , streptomyces c31 integrase gene(int ) , its attachment site ( attp ) and origin of dna transfer ( orit ) , aph(3)ii gene ( kan / neo resistance ) , and two 1 kb regions flanking the gene cluster on either side was used to capture and propagate the enterocin gene cluster . the vector pcap01 with the captured enc gene cluster from s. pacifica cnt-150 was named pbb01 . the plasmid pbb01 and its derivatives were conjugated into s. lividans tk23 and s. coelicolor m1146 using a standard triparental mating method with e. coli et 12567/pbb01 and e. coli et 12567/pub307 . after 6 days of growth in ssm media , the cultures were extracted with four volumes of etoac and concentrated in vacuo . the extracts were then dissolved in 100 l of mecn and analyzed by hplc using a luna 5u c18 column ( 150 mm 4.60 mm , 5 m beads ) with a linear gradient of 2100% mecn in water with 0.1% tfa over 30 min with a flow rate of 0.7 ml / min . hplc - hr - esi - msms analysis of all extracts was carried out on an agilent 1290 q - tof ( 2002000 m / z , 20 kev ) . the data were subjected to the molecular networking workflow and analyzed as described previously . the inactivation of the acyl - coa synthetase encoding gene , enc16 , in the heterologous host strain s. coelicolor m1146-pbb01 was done using -red recombination with an apramycin - resistant marker ( aac(3)iv ) as described previously .

heterologous expression of secondary metabolic pathways is a promising approach for the discovery and characterization of bioactive natural products . herein we report the first heterologous expression of a natural product from the model marine actinomycete genus salinispora . using the recently developed method of yeast - mediated transformation - associated recombination for natural product gene clusters , we captured a type ii polyketide synthase pathway from salinispora pacifica with high homology to the enterocin pathway from streptomyces maritimus and successfully produced enterocin in two different streptomyces host strains . this result paves the way for the systematic interrogation of salinispora s promising secondary metabolome .

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the most common ocular adverse event following the use of cyclosporine a ( csa ) 0.05% ophthalmic emulsion is ocular burning ( 17% ) . other adverse effects that have been reported include conjunctival hyperemia ( 1 - 5% ) , discharge , epiphora , eye pain , foreign body sensation , pruritus , stinging and blurred vision . here , we report a specific side effect of csa , namely eye drop - induced eyelash elongation in a patient with refractory giant papillary conjunctivitis . a 32-year - old female with giant papillary conjunctivitis on the left eye , who had undergone papillectomy 3 years previously and was refractory to topical steroid therapy , was treated with csa 0.05% ophthalmic emulsion ( restasis ) 4 times a day , preservative - frees artificial tears and gentamicin ophthalmic solution in the left eye . after 5 months of topical csa treatment , elongated eyelashes of her left eye were observed without other adverse effects . although hypertrichosis and trichomegaly have been documented in the literature as side effects of systemic csa , topical csa 0.05% eye drop - induced elongated eyelashes have not been reported , and we believe ophthalmologists should be mindful and inform patients about this specific side effect . a-32-year - old asian female patient , who had received conjunctival papillectomy on the left eye in 2002 , visited our ophthalmic outpatient department in 2007 complaining of a swollen eyelid and discharge from her left eye . the ocular examination revealed notable injected conjunctiva , especially over the superior part , and multiple papillae with injected and engorged vessels on the left eye ( fig . , she was started on topical steroid medications including fluorometholone 0.1% and prednisolone acetate 1% ophthalmic solutions for 2 months . however , steroid treatment was discontinued due to poor response and an elevated intraocular pressure . therefore , her treatment was switched to topical cyclosporine a ( csa ) 0.05% ophthalmic emulsion ( restasis ) 4 times a day , preservative - free artificial tears and gentamicin ophthalmic solution . after 5 months of topical csa treatment , she came back to our clinic complaining of elongated and darkened eyelashes on her left eye without other adverse effects ( fig . 2 ) . according to the patient , no systemic medications such as calcium channel blockers , erythropoietin or minoxidil were used during the treatment period . csa is a hydrophobic , cyclic polypeptide produced as a metabolite by the fungus tolypocladium inflatum . csa functions as an immunomodulating agent that binds to cyclophilin , a cytoplasmic protein , thus interrupting the signaling for interleukin ( il]-2 production , in addition to inhibiting the proliferation of cd4 t lymphocytes . it also has direct inhibitory effects on both eosinophil and mast cell activation , which has established its role in the treatment of allergic inflammation [ 2 , 3 ] . in the early 1980s , meanwhile , csa eye drops were also prescribed for patients with inflammatory ocular surface disorders , particularly dry eye syndrome and severe allergic keratoconjunctivitis . the major side effect of systemic csa is nephrotoxicity that is reversible with dosage reduction . other documented adverse reactions to systemic csa include mild hepatotoxicity , hypertension , dose - dependent hypertrichosis and trichomegaly , tremor , infection , gum hyperplasia , gastric irritation symptoms and neuropathies . on the other hand , adverse events following the use of csa 0.05% ophthalmic emulsion include ocular burning ( 17% ] , conjunctival hyperemia ( 1 - 5% ] , discharge , epiphora , eye pain , foreign body sensation , pruritus , stinging and blurred vision . however , to our knowledge , no csa ophthalmic emulsion - induced hypertrichosis has been reported in the literature to date . suggested that csa induces telogen follicles to enter an anagen growth phase , implying a role of csa in regulating the hair follicle immune system and its cellular components through the release of inhibitory / stimulatory cytokines [ 8 , 9 ] . the experiments also indicated that the rate of anagen induction is dependent on the dose , time course , and method of administration . in summary , although rarely encountered , csa 0.05% ophthalmic emulsion may induce the growth of eyelashes , and we believe ophthalmologist should be mindful and inform patients treated with topical csa about this side effect .

purposethe most common ocular adverse event following the use of cyclosporine a ( csa ) 0.05% ophthalmic emulsion is ocular burning ( 17% ) . other adverse effects that have been reported include conjunctival hyperemia ( 1 - 5% ) , discharge , epiphora , eye pain , foreign body sensation , pruritus , stinging and blurred vision . here , we report a specific side effect of csa , namely eye drop - induced eyelash elongation in a patient with refractory giant papillary conjunctivitis.designobservational case report.methodscase report and review of the literature.resultsa 32-year - old female with giant papillary conjunctivitis on the left eye , who had undergone papillectomy 3 years previously and was refractory to topical steroid therapy , was treated with csa 0.05% ophthalmic emulsion ( restasis ) 4 times a day , preservative - frees artificial tears and gentamicin ophthalmic solution in the left eye . after 5 months of topical csa treatment , elongated eyelashes of her left eye were observed without other adverse effects.conclusionalthough hypertrichosis and trichomegaly have been documented in the literature as side effects of systemic csa , topical csa 0.05% eye drop - induced elongated eyelashes have not been reported , and we believe ophthalmologists should be mindful and inform patients about this specific side effect .

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in recent years , corneal specialists have shown a fast growing interest in collagen crosslinking using the photosensitizer riboflavin and ultraviolet a light as a new therapeutic alternative for the treatment of progressive keratoconus . the aim of this treatment is to modify the biomechanical properties of the cornea , thus increasing its rigidity and preventing the progression of keratoconus.1 promising results have been published recently , and data from the dresden clinical study have shown stabilization of the disease , even after 5 years.2,3 it is necessary to follow strict treatment settings and patient eligibility criteria to avoid serious ocular side effects . the patient s cornea must be irradiated with a small peak - like sector of the ultraviolet a spectrum ( 370 nm ) with 3 mw / cm irradiance for 30 minutes , which corresponds to a dose of 5.4 j / cm.3 the ultraviolet a irradiance must be checked before each treatment using an ultraviolet a meter to ensure that the optimal irradiance dose is delivered . the photosensitizing riboflavin 0.1% solution must be applied 5 minutes before irradiation and every 5 minutes during irradiation . it is also essential to perform preoperative pachymetry on each patient to exclude those with extended areas of less than 400 m of stromal thickness . we describe how to perform collagen crosslinking in the protocol setting using a slightly modified ultraviolet a dermatological lamp and preparing the riboflavin 0.1% solution inhouse . we used a slightly modified 370 nm ultraviolet a lamp ( uv 109a , waldmann , villingen - schwenningen , germany ) designed for dermatological treatment ( figure 1a ) , covered with a black plastic adhesive tape leaving a small window through which ultraviolet light can reach the cornea ( figure 1b ) . the desired irradiance of 3 mw / cm is tested with a ultraviolet a meter ( waldmann ) before each treatment , thus establishing the optimal distance from the ultraviolet a lamp to the cornea . the lamp was held by a clamp mounted on an intravenous pole ( figure 2 ) . patients corneas were irradiated with 3 mw / cm of ultraviolet a ( 370 nm ) for 30 minutes . the riboflavin 0.1% solution was prepared just before treatment by mixing 10 mg of riboflavin-5-phosphate ( guinama , valencia , spain ) with 10 ml of dextran 20% solution . the solution was introduced into an empty 15 ml balanced salt solution bottle ( alcon laboratories , fort worth , tx , usa ) wrapped in aluminum foil to avoid exposure of the riboflavin to ambient light ( figure 3 ) through a 0.22 m sterilization filter ( millipore corporation , bedford , ma , usa ) . the riboflavin 0.1% solution was applied 5 minutes before irradiation and every 5 minutes during irradiation . thus far , we have successfully treated 12 patients with progressive keratoconus using this ultraviolet a lamp and riboflavin 0.1% solution ( figure 4 ) prepared inhouse . the riboflavin solution was also easily prepared in the clinical pharmacy of the hospital by trained personnel . one important issue to be mentioned is the fact that the limbus should be protected against irradiation , and a round 8 mm hole in the tape that covers the lamp could be made for this purpose . the price of a commercially available ultraviolet a lamp designed for collagen crosslinking is approximately 15,000 , and the riboflavin solution prepared inhouse costs approximately 60 per patient . the price of the slightly modified ultraviolet a dermatological lamp we used is approximately $ 400 , the riboflavin 0.1% solution we prepared inhouse costs $ 2.20 per patient , and the ultraviolet light meter price costs around $ 200 . this provides ophthalmologists worldwide with an affordable alternative device for collagen crosslinking , especially for those in developing countries or places where resources are limited .

in this paper , we describe an original , affordable , and available device for performing collagen crosslinking . this is carried out in a safe and reproducible way by means of a simple modification to an affordable ultraviolet a lamp and by preparing riboflavin 0.1% solution inhouse .

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as a service to our authors and readers , this journal provides supporting information supplied by the authors . such materials are peer reviewed and may be reorganized for online delivery , but are not copyedited or typeset . technical support issues arising from supporting information ( other than missing files ) should be addressed to the authors .

abstractwe observe the diffusion anisotropy difference between singlet and triplet excitons in organic crystals ; that is , singlet and triplet excitons may have completely different spatial direction preference for diffusion . this phenomenon can be ascribed to the distinct dependence of different excitonic couplings ( coulomb frster vs. exchange dexter ) existing in singlet and triplet excitons on their intermolecular distance and intermolecular orientation . such a discovery provides insights for understanding the fundamental photophysical process in a vast range of organic condensedphase systems and optimizing the efficiency of organic optoelectronic materials .

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the year 2006 may be remembered in history as the year of the amphioxus . european agencies failed to fund ( or we european researchers failed to convince the agencies of the importance of the amphioxus genome ) . fortunately , at the other side of the atlantic , linda holland ( scripps institution , university of california ) and jeremy gibson - brown ( washington university ) did not fail . they collaborated on a white paper to the joint genome institute of the department of energy 1 that was supported by the relatively few labs concentrated on amphioxus research . [ ricard albalat ( spain ) , marianne bronner - fraser ( usa ) , hector escriv ( france ) , jordi garcia - fernndez ( spain ) , kaoru kubokawa ( japan ) , vincent laudet ( france ) , thruston lacalli ( canada ) , leo pezzement ( usa ) , georgia panopoulou ( germany ) , mario pestarino ( italy ) , pierre pontarotti ( france ) , t.v . ventakatesh ( usa ) , hiroshi wada ( japan ) , ulrich welsch ( germany ) , kinya yasui ( japan ) , and shi - cui zhang ( china ) ] . a number of outstanding scientists outside the amphioxus community also gave support to the proposal ( the list is available in ref 1 ) . that the amphioxus genome was crucial to the understanding of the origin of the human genome maybe was not clear to funding agencies but it was for the human genome consortium , as in the landmark human genome paper in 2000 2 : our results so far are insufficient to settle whether two rounds of wgd occurred around 500 myr ago [ ... ] . another approach to determining whether a widespread duplication occurred at a particular time in vertebrate evolution would be to sequence the genomes of organisms whose lineages diverged from vertebrates at appropriate times , such as amphioxus ) . led by dan rokhsar ( jgi ) , and also thanks to the est collections made by the team of nori satoh ( kyoto university ) in collaboration with jr - kai yu and linda holland ( university of california ) we are about to know it : are we , human , octaploid ? and which were the gene novelties ( if any ) that characterised chordate evolution ? coming soon , very soon ... and second , the big drama with amphioxus : how they do it . to be a model , a genetic , developmental and functional one , amphioxus has to allow researchers to use its eggs and sperm ! and they do it not very often , the american species branchiostoma floridae once every two weeks in the summer , and not much more often the eastern species b. belchei . still , pioneer experiments of gene knockdown , reporter constructs , and cell lineage have been performed 3 - 5 . as with the genome , there is a big new , again not thanks to the european funding agencies , but to the effort of european research groups . an amphioxus consortium headed by hector escriv ( banyuls sur mer ) and composed by members of the labs in barcelona , lyon , paris and genova have been , during three years , trying to understand the reproductive behaviour of the european amphioxus , b. lanceolatum ( fig . now , nearly every day , we are able to obtain eggs and sperm on demand during the breeding season ( april - july ) 6 . this is possible not only in place , at the laboratoire arago , the marine station at banyuls sur mer . but also in our laboratory in barcelona . as far as we know , this is the only dry lab ( not a marine station ) in where amphioxus eggs and sperm are obtained in a controlled manner , a small but big step towards the dream : developing amphioxus as an experimental model system ( fig . most of the amphioxus researchers that have fought for the genome and the embryos are giving their particular data or views in their particular area of research . this second part focuses particularly in the nervous system , one of the major steps forwards to the complexity of vertebrates . homologies , innovations , brain , neural crest , colinearity , ... , interesting , promising and provocative hypothesis arise from the study of our lovely little lancelet . genome by the corner , embryos by the hand , things are getting better , every day . amphioxus in the lab : banyuls ( left ) , barcelona ( center ) and egg injection system ( right ) . developmental series of the amphioxus branchiostoma floridae . photograph courtesy of hector escriv .

the genome of the amphioxus is on the horizon . with linda holland and jeremy gibson - brown at the forefront , with all the amphioxus community behind , and with the joint genome institute , the amphioxus genome will see the light this year , 2006 . hope that it will reflect the prototypical preduplicative genome of vertebrates . it may answer definitively what the human genome did not : are we vertebrates octaploid ? will it shed light on the novelties that helped non - chordates to be chordates ? and more , will amphioxus , with a simpler genome , be developed to a senior experimental model system , allowing the testing of molecular functions in a non - duplicated genome background and allowing genetic modification to recapitulate evolution ? thanks to an outstanding collaboration between labs , the laboratory culture of amphioxus is underway after years of hard work in the field . 2007 looks promising for amphioxus research .

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this prospective interventional case series was approved by the review board / ethics committee of the ophthalmic research center of the university . five eyes of 5 patients with diagnosis of refractory csc ( lasting more than 1 year ) were included in this study . diagnosis was made by the history of recurrent blurred vision and metamorphopsia for more than one year , detection of neurosensory detachment in ophthalmoscopy and optical coherence tomography ( oct ) , and observation of active rpe leakage in flourscein angiography . exclusion criteria consisted of any accompanying macular disease , severe media haziness which precludes oct evaluation , and noncompliance . all eyes received a single injection of 0.05 ml ( 1.25 mg ) intravitreal bevacizumab ( avastin ; genentech inc . , south san francisco , ca , usa [ made for f. haffmann - la roche ltd . , basel , switzerland ] ) performed by a 30-guage needle through supratemporal quadrant 4 mm from the limbus under sterile condition . all patients underwent a through ophthalmic examination 1 day , 1 week , and 1 , 2 , and 6 months after the injection . best corrected visual acuity ( bcva ) of the eyes was checked by a masked optometrist . it was changed to the logarithm of minimum angle of resolution ( logmar ) scale for statistical purposes and compared at months 2 and 6 with the baseline values . central macular thickness ( cmt ) measured by oct ( 3d oct-1000 ; topcon corporation , tokyo , japan ) was performed at presentation and repeated 6 months after the intervention . it was measured in a 1-mm circle centered on the fovea by an optician who was masked to the study . none of the patients had history of intraocular surgery , diabetes mellitus , hypertension , cardiovascular disease and smoking . an increase of bcva was noticed during the follow - up in all eyes except case 1 . mean bcva at baseline was 0.60 0.25 that improved to 0.42 0.16 and 0.24 0.21 logmar up to the month 2 and 6 , respectively . this improvement at 2 months did not reach to a meaningful level ( p = 0.064 ) ; however , it was statistically significant at 6 months ( p = 0.025 ) . no recurrence was observed in any of the eyes during the follow - up period . central macular thickness decreased significantly from 370 65 m at baseline to 210 24 m at 6 months after injections ( p = 0.009 ) ( table 2 ) . none of the eyes had intraocular pressure rise ( > 21 mmhg ) or cataract progression during the follow - up period . they include acetazolamide , beta - blockers , vitamins , and non - steroidal anti - inflammatory drugs . there are some controversial recommendations in the literature on the use of laser photocoagulation in this field . some authors reporting that laser photocoagulation shortens the duration of disease and reduces recurrence rate , while others maintain that it does not affect final vision and recurrence rate . furthermore , laser may be associated with permanent scotoma which may enlarge over time with rpe scar expansion , as the possible development of cnv . it may hasten resolution of exudation by reducing choroidal blood flow and hence favoring cessation of leakage . most recently , several case series have reported the use of indocyanine green guided pdt in the treatment of chronic csc . ober et al . reported the successful treatment of focal rpe leaks in csc by pdt in a small pilot series which showed resolution and visual improvement . cardillo piccolino et al . performed indocyanine green guided pdt in 16 eyes with chronic csc and treatment resulted in complete resolution of serous retinal detachment 1 month after treatment in 75% of eyes . at 3 months after pdt , 69% of eyes had visual improvement of 1 or more lines . however , 31% of their cases developed secondary rpe changes at the site of pdt , which were thought to be due to hypoxic damage caused by choriocapillaris occlusion . our study showed a significant visual improvement and cmt reduction following single injection of ivb ( 1.25 mg ) in 5 cases suffering from refractory csc for more than one year . in a similar study on 5 cases with csc , torres - soriano et al . noticed an improvement in bcva , fluorescein angiographic leakage , and reduced or resolved neurosensory detachment . however , they injected 2.5 mg ivb and included cases with history of decreased visual acuity more than 3 months , recurrent episodes of csc or even acute cases with excessive discomfort about visual acuity . in a case . showed that in cases with chronic csc ivb injection improved bcva and reduced cmt . however , they performed multiple injections of 2.5 mg ivb at 6 to 8 week intervals ( range , 1 to 4 weeks ) . however , recurrence did not occur in any case of our study during follow up period . in summery , the present study demonstrated a promising effect of ivb in the treatment of refractory csc ; however , we can not make specific treatment recommendations based on this small , uncontrolled case series .

in a clinical case series , 5 patients with not - resolved central serous choroidoretinopathy ( csc ) lasting more than 1 year received one intravitreal bevacizumab injection ( ivb , 1.25 mg ) injection . all patients underwent a through ophthalmic examination 1 day , 1 week , and 1 , 2 , and 6 months after the injection . best corrected visual acuity ( bcva ) and central macular thickness were compared before and after treatment by optical coherence tomography . mean bcva was improved significantly ( p = 0.020 ) from 0.60 0.25 to 0.50 0.18 and 0.29 0.19 logarithm of minimum angle of resolution at 6 and 18 weeks , respectively . central macular thickness was also decreased significantly ( p = 0.010 ) from 370 65 to 208 23 m at 4 months . no recurrence was occurred during follow - up . ivb injection may have beneficial effect in the treatment of refractory csc .

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the patient was a 25-year - old , right - handed woman who presented two months after the sudden onset of lower extremity paresthesias and sensory loss that extended into the abdomen and lower chest and one episode of urinary urgency and subsequent incontinence . her examination was notable for brisk lower extremity deep tendon reflexes but no other abnormalities . mri of the cervical and thoracic spine revealed both cervical and midthoracic plaques consistent with demyelination . a subsequent brain mri revealed five scattered , nonenhancing , white - matter lesions ; including a large ( approximately 5 mm in diameter ) lesion involving the corpus callosum and two lesions perpendicular to the left lateral ventricle . her b12 level , htlv-1 antibodies , vitamin e level , rpr , ana , and lyme titre were all within normal limits she was started on glatiramer acetate following her clinically isolated syndrome of partial transverse myelitis and mri findings confirming dissemination in space . two and a half years after her initial presentation , she developed right hemiparesis that resolved over a few days following treatment with intravenous steroids . she had a subsequent similar episode of left hemiparesis and hemisensory deficit two months after that , confirming a diagnosis of clinically definite multiple sclerosis . one year after her initial presentation , she developed a sudden onset of discomfort in her legs associated with an urge to move that was worse at night and impaired sleep . the symptom resolved while walking and had been present for only 3 - 4 days at the time of presentation . her last menstrual period was two weeks prior to this presentation , and she was faithfully using an oral contraceptive . her iron level was 108 mcg / dl , iron saturation was 28.6% , and ferritin was 94 ng / ml . her symptoms resolved a few days after a course of intravenous methylprednisolone ( 1 g daily for three days ) , and she had no recurrence over the next three years . restless legs syndrome is a movement disorder characterized by distressing urge to move the legs ( akathisia ) associated with discomfort and that is brought on by rest , relieved by movement or walking , and become worse at night or in the evening . her rather abrupt onset suggested the possibility of restless legs syndrome secondary to an underlying cause , such as pregnancy or iron deficiency . however , her diagnostic evaluation excluded these possibilities , and her clinical course and probable response to steroids suggested that her restless legs syndrome was due to an acute exacerbation of her multiple sclerosis . several studies have reported an increased incidence of restless legs syndrome in patients with multiple sclerosis , have suggested both a role for restless legs syndrome in ms - related fatigue , and have suggested that multiple sclerosis is a cause of secondary restless legs syndrome [ 25 ] . however , none of these studies describe self - limited restless legs syndrome occurring as an acute exacerbation of multiple sclerosis as in this case . manconi et al . demonstrated a correlation between rls and cervical cord lesion burden . this patient had a known cervical cord plaque , and this correlation might also explain why no new intracranial lesion was detected during her acute presentation with rls . restless legs syndrome is commonly idiopathic , but it has been associated with a number of conditions other than multiple sclerosis , including pregnancy , renal failure , peripheral neuropathy , and iron deficiency [ 1 , 7 ] . iron deficiency has been recognized in several studies as a cause for secondary restless legs syndrome , particularly at serum ferritin concentrations of less than 50 ng / ml [ 710 ] . the pathophysiology of even idiopathic restless legs syndrome is probably related to low brain iron levels . mri , csf , and neuropathological studies have all implicated central nervous system iron deficiency in the pathophysiology of restless legs syndrome , even in the absence of systemic iron deficiency [ 1116 ] . recently , there has been interest in the role of iron in ms and iron deposition because cerebral venous insufficiency has been suggested as a proposed mechanism for the disease . haacke et al . reported mri evidence of iron accumulation in the basal ganglia and thalamus of ms patients . furthermore , iron appears to be an important cofactor in cns myelination , and van toorn et al . have reported two cases of iron deficiency associated with tumefactive demyelination in children [ 2022 ] . the pathophysiology of ms consists of both an inflammatory demyelinating component and an axonal degeneration component . levine et al . reported normal csf ferritin , transferrin , and iron concentrations in ms patients with stable or relapsing and remitting ms , but elevated levels in the csf of patients with chronic progressive ms . therefore , it is likely that the pathophysiology of rls in ms patients is related to the inflammatory , demyelinating component of the disease which may be associated with low or normal cns iron levels , rather than due to axonal degeneration , which is associated with cns iron accumulation . the observation that rls is associated with spinal cord plaques would also suggest a relationship to the inflammatory and demyelinating component of disease . this patient , presenting with transient rls due to an acute , inflammatory exacerbation of her multiple sclerosis , further supports the notion that the pathophysiology of rls in multiple sclerosis is related to autoimmune inflammatory demyelination .

restless legs syndrome is common in patients with multiple sclerosis but has not been reported as occurring due to an acute , inflammatory , demyelinating attack . restless legs syndrome is known to be related to low brain iron levels . multiple sclerosis has been associated with the abnormal accumulation of iron in the chronic , progressive phase of axonal degeneration . iron deficiency may play a role in demyelination . this suggests that restless legs syndrome may be caused by the inflammatory , demyelinating component of multiple sclerosis rather than axonal degeneration . the author presents a case of self - limited restless legs syndrome occurring as an acute attack of multiple sclerosis , supporting the notion that inflammatory demyelination is the underlying pathophysiology of restless legs syndrome in multiple sclerosis .

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present the results of an exploratory study which aimed to identify the attributes of relational continuity as conceived by the actors involved in the organization of services to frail older people . the lengthening of the duration of life with autonomy loss warrants a transformation of the response to the needs of older people . the organization of services must evolve from a hospital - centered model to a residence - centered model better adapted to long - term care . this refocus on residential care provokes a multiplication of service providers which must be coordinated to ensure continuity of care . amongst the three forms of continuity ( informational , management and relational ) twenty - seven interviews with practitioners , managers , family caregivers and users were conducted and analysed using a content analysis approach . while the family caregivers and users stressed the psycho - affective nature of the care relationship , the practitioners viewed it as a means to ensure the adequacy of services . from the user 's viewpoint , the relationship is not the responsibility of one professional , but of a collective effort that may carry his voice across the services organization .

purposepresent the results of an exploratory study which aimed to identify the attributes of relational continuity as conceived by the actors involved in the organization of services to frail older people.theorythe lengthening of the duration of life with autonomy loss warrants a transformation of the response to the needs of older people . the organization of services must evolve from a hospital - centered model to a residence - centered model better adapted to long - term care . this refocus on residential care provokes a multiplication of service providers which must be coordinated to ensure continuity of care [ 1 ] . amongst the three forms of continuity ( informational , management and relational ) [ 2 ] , relational continuity appears as the least documented and most difficult to measure.methodstwenty-seven interviews with practitioners , managers , family caregivers and users were conducted and analysed using a content analysis approach.results and conclusionswhile the family caregivers and users stressed the psycho - affective nature of the care relationship , the practitioners viewed it as a means to ensure the adequacy of services . from the user 's viewpoint , the relationship is not the responsibility of one professional , but of a collective effort that may carry his voice across the services organization .

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cytomegalovirus ( cmv ) colitis is common among immunocompromised patients who are more prone to opportunistic infections . after the infection of cmv is detected by histology or serology , antiviral treatment is usually chosen initially . since cmv disease can not be diagnosed on clinical symptoms alone , diagnosis and treatment are sometimes delayed . here , we report a case of a hemorrhagic cmv colitis that occurred in an immunocompromised patient after a colectomy due to colon cancer and was successfully treated with ganciclovir . an 85-year - old woman underwent esophagogastroduodenoscopy and colonoscopy for investigation of anemia . a laterally spreading tumor of the granular type , 85 mm in diameter , although magnifying image - enhanced colonoscopy suggested a tubulovillous adenoma , surgical resection , not endoscopic mucosal resection , was chosen because of the size of the tumor . however , as she had a medical history including breast cancer , myocardial infarction , general edema due to chronic renal failure ( oral administration of prednisolone 5 mg / day ) , diverticulosis of sigmoid colon , and bilateral ureteral stent placement due to retroperitoneal fibrosis , she did not want to take medical treatment anymore but to monitor her own condition for a while . after 3 months , she finally agreed to have surgery and was admitted to our hospital . the patient underwent ileocecal resection followed by stapled functional end - to - end anastomosis ( fig . the postoperative course was favorable ; dietary intake and oral drug administration were started on postoperative day 4 and both flatus and stool passed . however , she had sudden abdominal pain and heavy bloody discharge on postoperative day 11 . although conservative treatment , including blood transfusion therapy for anemia , was performed initially , there was no improvement after a week . in addition to the endoscopic findings , the patent 's immunocompromised state suggested possible cmv colitis . because cmv antigen was confirmed in peripheral blood samples , intravenous antiviral treatment was started from the postoperative day 23 ( ganciclovir , 150 mg / day ) . after 4 days of the treatment , bloody discharge stopped , and at 8 days , improvement of abdominal pain was observed . the antiviral treatment was continued for 2 weeks until the serological confirmation of negative cmv antigen . after improvement of the colitis - related symptoms , the patient was discharged from our hospital . cmv infection often develops a latent infection with no signs or symptoms after acute infection . although most people are exposed to cmv in their lifetime , typically only the patients with weakened immune systems , such as aids , malignancy , organ transplant or bone marrow transplant , and steroid or immunosuppressive treatments , become ill by reactivating cmv and present with cmv pneumonia , gastroenteritis , retinitis , and encephalitis . cmv disease is often diagnosed by pathologic and serologic confirmation because clinical symptoms are not specific . furthermore , colonoscopic findings of cmv colitis mimic many conditions , including pseudomembranous colitis , ischemic colitis , ulcerative colitis and crohn 's disease . in our case , as we initially considered the bleeding from the diverticulum or anastomosis , conservative treatment was chosen . after one week of conservative therapy , there was no sign of improvement in bloody discharge ; therefore , we decided to perform colonoscopy . we were hesitant to perform colonoscopy due to our patient having had a colectomy . according to the meta - analysis of cmv colitis in immunocompetent hosts , the highest mortality rates were associated with immune modulating conditions that include 16 patients . of those analyzed , 5 patients ( 31.3% ) received colectomy as initial treatment and 8 patients ( 50% ) and 6 patients ( 37.5% ) had coexisting renal failure and diabetes mellitus , respectively . in our case , as the patient was given steroids due to chronic renal failure and the colonoscopy revealed the longitudinal ulcer at the anastomosis , we were able to suspect cmv colitis and confirmed the diagnosis serologically . because endoscopic biopsy was not performed , cmv infection was not evaluated histologically . of note , we performed immunohistochemistry of cmv protein using resected colon cancer specimen , though cmv - positive stain was not detected . this result seems to relate with the fact that cmv is not associated with carcinogenesis and reactivation of latent cmv infection causes cmv colitis [ 5 , 6 ] . the first choice of treatment of cmv infection is antiviral therapy [ 7 , 8 ] . systemic antiviral treatment has provided significant advances and has resulted in dramatically improved outcomes [ 7 , 8 ] . treatment time usually ranges from 1 to 4 weeks , depending on the treatment effect such as improvement of the symptoms and/or confirmation of the negative cmv antigen . in our case , despite the necessity of reducing the dose of ganciclovir due to renal failure , the patient showed good response to systemic therapy and did not require further treatment . fortunately , as she did not show uncontrollable heavy bleeding or symptoms of bowel perforation , surgical resection was not needed . the case we mentioned above can potentially occur in immunocompromised patients . with recent progress in medicine , the number of high - risk patients who undergo surgery is increasing ; therefore , the reactivation of latent cmv infection in immunocompromised patients should be actively considered for the differential diagnosis , leading to timely diagnosis and appropriate treatment .

we report a case of hemorrhagic cytomegalovirus ( cmv ) colitis , occurring in a postoperative patient due to a weakened immune system . an 85-year - old woman with a medical history , including chronic renal failure treated with oral administration of prednisolone , underwent colectomy due to an ascending colon cancer . while the postoperative course was favorable , she exhibited acute severe abdominal pain and massive bloody discharge after 11 days of surgery . her colonoscopic examination showed multiple longitudinal ulcers on the anastomosis . in addition to these endoscopic findings , her past medical history helped suggest cmv colitis . because serological testing revealed positive cmv antigen , she was finally given a diagnosis of cmv colitis and received intravenous ganciclovir for the initial treatment . hemorrhagic cmv colitis after colectomy is an important postoperative complication ; we therefore present our case with diagnosis and treatment experience .

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dopa - responsive dystonia ( drd ) is characterized by childhood - onset dystonia and a dramatic and sustained response to administration of low - doses of oral levodopa . this disorder typically presents with gait disturbance , caused by lower limb dystonia with diurnal variation , a positive family history , and gradual progression to generalized dystonia . a ten - year - old girl was brought with complaints of difficulty in walking and stiffness of both lower limbs , for the past six months . she also had a history of frequent falls while walking and was unable to stand for prolonged periods . her antenatal , birth , and neonatal periods were uneventful and developmental milestones were appropriate for her age . her higher mental functions were normal , speech was hypophonic ; she had a gait disturbance characterized by leg stiffness , and a tendency to walk in an equinus posture , resulting in difficulty in balancing . her tone was slightly increased in all the four limbs , with cog - wheel rigidity . deep tendon reflexes in all the four limbs were exaggerated with extension of both great toes ( striatal toes ) . , it was found that the symptoms and signs were relatively mild in the morning during rounds , whereas , they gradually worsened as the day progressed , rendering the child almost unable to walk by evening . magnetic resonance imaging ( mri brain and spine were normal . in view of the typical diurnal variation of dystonia , a therapeutic challenge with levodopa / carbidopa was tried and there was a dramatic decrease in dystonia within two days and the child 's gait improved . the child was treated with a combination of levodopa , carbidopa , and trihexyphenidyl . on follow - up genetic studies were planned , but could not be done due to lack of resources . drd is an inherited disorder characterized by dystonia with diurnal variation and favorable response to levodopa / carbidopa . the inheritance is usually autosomal dominant ; however , autosomal recessive inheritance is also seen in some cases . the enzyme deficiency responsible for the manifestations is gtp cyclohydrolase 1 ( gch ) , which is a rate - limiting enzyme in the synthesis of dopamine . this disorder had been referred to as hereditary progressive basal ganglia disease , hereditary progressive dystonia with marked diurnal variation , segawa disease , and drd in the past . at present , segawa disease specifically denotes an autosomal dominantly inherited mutation in the gch 1 gene located on chromosome 14q22.1 to q22.2 . the disease usually manifests in school age children , however , adults with the disease have also been reported . initial manifestations of this disease include postural dystonia of the lower limbs with characteristic equino varus deformity of both feet . the dystonia gets worse as the day progresses , becomes maximal by evening , and decreases after sleep by morning . investigations characteristically reveal low levels of pteridine metabolites in the cerebrospinal fluid , normal neuroimaging , and increased blood phenylalanine levels after phenylalanine loading tests . assessing the therapeutic response to levodopa is a useful and recommended method of diagnosing drd , when the diagnosis is in doubt and when dystonia is not attributable to hypoxic ischemic encephalopathy . in one reported series , administration of low - dose levodopa had resulted in complete to near - complete recovery of symptoms in a cohort of chinese patients , with no significant long - term side effects . in our case , the child presented with gait disorder characterized by dystonic movements of the lower limbs of gradual onset , which disappeared during sleep , and reappeared after getting up from bed and progressively worsened throughout the day with symptoms , for the past six months . with the above - mentioned clinical findings and a dramatic response to the levodopa / carbidopa combination children with recent onset dystonia and gait abnormalities may pose a diagnostic challenge . a careful history and focused neurological examination , looking for diurnal variation in symptoms , holds the key in arriving at the diagnosis . in such children a therapeutic response to levodopa might be a safe and appropriate way of confirming drd .

children with recent onset dystonia and gait abnormalities may pose a diagnostic challenge . a ten - year - old , developmentally normal girl , presented with a six - month history of gait abnormality and dystonia . her complaint worsened as the day progressed . in view of typical diurnal variation of dystonia , a therapeutic challenge with levodopa / carbidopa was given and there was a dramatic response . hence , a diagnosis of dopa - responsive dystonia ( drd ) was made . drd is an inherited disorder characterized by dystonia with diurnal variation and favorable response to levodopa / carbidopa . the inheritance is usually autosomal dominant , however , in some cases , autosomal - recessive inheritance is also seen .

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