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there is an increased incidence of major and minor congenital abnormalities in infants born to epileptic mothers ( 6 - 7% compared with 2c3% in the general population ) . sodium valproate is a popular drug because of its broad range of anticonvulsant effects and relative freedom from sedative and behavioral effects . exposure to valproic acid during first trimester can result in the constellation of minor craniofacial anomalies and major organ malformations in human fetuses . here , we report a case of a 3-month - old baby with facial dysmorphism , as a case of fetal valproate syndrome ( fvs ) based on the phenotype and maternal use of valproic acid during the antenatal period . a 3-month - old male child admitted with complaints of breathlessness since 3 days with fever . it was a full - term normal delivery with birth weight of 2.5 kg without any postnatal complications . mother was known case of epilepsy and was controlled on sodium valproate 800 mg / day since 3 years . before delivering this child mother had three spontaneous abortions within first trimester during those 3 years . on admission , the child was in congestive cardiac failure with heart rate-168/min , respiratory rate - 64/min . child had severe failure to thrive with current weight 3.8 kg at 3 months of age despite on exclusive breastfeeding . features of facial dysmorphism [ figure 1 ] such as prominent metopic sutures , trigonocephaly , tall forehead , epicanthal folds , infraorbital groove , and medial deficiency of eyebrows , shallow philtrum , anteverted nares , and broad root of nose , low set ears , thin upper lip , and small mouth were present . broad hands and feet , loose skin [ figure 2 ] , and hypospadias were other features . based on facial dysmorphism , congenital heart disease and hypospadias in the setting of maternal valproic acid consumption during antenatal period , diagnosis of fvs prominent metopic suture fetal valproate syndrome on auscultation , pansystolic murmur with loud pulmonary component of second heart sound were present . two - dimensional echocardiography showed moderate atrial septal defect , ventricular septal defect with tiny patent ductus arteriosus with moderate pulmonary hypertension . ophthal evaluation , ultrasonography abdomen , and x - ray spine were within normal limits . valproic acid crosses the placenta and is present in a higher concentration in the fetus than in the mother . complications of epilepsy and antiepileptic drug treatment , include stillbirths , prematurity , low birth weight , major and minor malformations , and cognitive delay later in life . following several other case reports of the teratogenic effects of vpa , all of which documented similar major and minor anomalies . the facial features seen in fvs are trigonocephaly , tall forehead with bifrontal narrowing , epicanthic folds , infraorbital groove , medial deficiency of eyebrows , flat nasal bridge , broad nasal root , antiverted nares , shallow philtrum , long upper lip and thin vermillion borders , thick lower lip , small downturned mouth . our patient had almost all facial features of fvs that has previously been described in literature . the timing of exposure and the dose of the drug are important in influencing the outcome of pregnancy . first - trimester exposures are more likely to result in malformations as this is the main period of structural development in the fetus . the efficacy of valproic acid as an antiepileptic drug can not be disputed , but the extent of its teratogenic effects can not be under - estimated either . hence , the balance between the therapeutic effects of this drug and its teratogenic effects is critical in the management of women with epilepsy . high - dose folic acid ( 4 mg / day ) is recommended during pregnancy , starting at least 6 weeks preconception and continuing through the first trimester .

antenatal use of anticonvulsant valproic acid can result in a well - recognized cluster of facial dysmorphism , congenital anomalies and neurodevelopmental retardation . in this report , we describe a case with typical features of fetal valproate syndrome ( fvs ) . a 26-year - old female with epilepsy controlled on sodium valproate 800 mg / day since 3 years , gave birth to a male child with characteristic features of fvs . she also had 3 spontaneous first - trimester abortions during those 3 years . sodium valproate , a widely used anticonvulsant and mood regulator , is a well - recognized teratogen that can result in facial dysmorphism , craniosynostosis , neural tube defects , and neurodevelopmental retardation . therefore , we strongly recommend avoidance of valproic acid and supplementation of folic acid during pregnancy .

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the female child is six - years - old and comes from fortaleza in the state of ceara in brazil . initial symptoms began six months ago and included fever , asthenia , and weight loss . tests findings include : cbc : normochromic and very microcytic anemia ( hb : 7.1 g ) , leucopenia ( 3,300 wbc ) , and thrombopenia ( 70,000 platelets / mm ) ; esr : 77 mm for first hour ; serology of leishmaniasis : positive ( 1/1600 using immunofluorescence and 5 archs in electrosyneresis ) ; bone marrow biopsy : the medulla is rich , but no leishmania are seen . the patient is given a meglumine antimoniate treatment with increasing doses reaching 60 mg / kg / day after three days . transient hepatic cytolysis emerges with alanine transaminasi ( alt ) and aspartate aminotransferase ( ast ) 1.5 times above upper normal limit . according to the world health organization , leishmaniasis is a poverty - related disease whose public health impact has been , until recently , grossly underestimated . the disease is caused by protozoan parasites belonging to the genus leishmania that are transmitted by the bite of a phlebotomine sandfly . there are approximately two million new cases each year 1.5 million of cutaneous leishmaniasis and 500,000 of visceral leishmaniasis or kala - azar . kala - azar is endemic to south america , east africa , the mediterranean basin , the middle east , india , and china . the cardinal sign of kala - azar is an anarchic type of fever resisting all forms of treatment . the disease always yields splenomegaly and is thought by many to produce the largest spleens in parasitology . contrary to adult manifestations , cutaneous signs such as erythematous , hyper- or hypopigmented papules and nodules of various sizes are rare in children . although not performed in the case reported , protein immunoelectrophoresis reveals hypergammaglobulinemia with an igg peak in patients with kala - azar . serological tests , which are useful for the diagnosis of kala - azar , include elisa ( enzyme linked immunosorbent assay ) , direct agglutination test ( dat ) , indirect fluorescent antibody test ( ifat ) , and the rk39 dipstick test . elisa is widely performed , particularly in epidemiological studies , because it is very simple . anemia secondary to kala - azar is aregenerative because of bone medullar parasitic invasion . even without direct evidence of leishmania , this child s poor health condition coupled with the epidemiological , clinical , and biological presentations called for immediate treatment . in brazil , side - effects of this case s treatment drug of choice , meglumine antimoniate , include the following : i ) intolerance that usually appears after the first injections and consists of fever , chills , cough , myalgia , and/or skin rash . treatment discontinuation is mandatory if such intolerance occurs ; ii ) intoxication resulting in fever , cough , skin rash , polyneuritis , hepatitis , cardiac , and renal signs . alternative treatments for kala - azar include sodium stibogluconate , amphotericin b , liposomal amphotericin b , pentamidine , and paromycin . the cardinal sign of kala - azar is an anarchic type of fever resisting all forms of treatment . the disease always yields splenomegaly and is thought by many to produce the largest spleens in parasitology . contrary to adult manifestations , cutaneous signs such as erythematous , hyper- or hypopigmented papules and nodules of various sizes are rare in children . although not performed in the case reported , protein immunoelectrophoresis reveals hypergammaglobulinemia with an igg peak in patients with kala - azar . serological tests , which are useful for the diagnosis of kala - azar , include elisa ( enzyme linked immunosorbent assay ) , direct agglutination test ( dat ) , indirect fluorescent antibody test ( ifat ) , and the rk39 dipstick test . elisa is widely performed , particularly in epidemiological studies , because it is very simple . anemia secondary to kala - azar is aregenerative because of bone medullar parasitic invasion . even without direct evidence of leishmania , this child s poor health condition coupled with the epidemiological , clinical , and biological presentations called for immediate treatment . in brazil , the etiological agent of kala - azar is leishmania donovani . without treatment , side - effects of this case s treatment drug of choice , meglumine antimoniate , include the following : i ) intolerance that usually appears after the first injections and consists of fever , chills , cough , myalgia , and/or skin rash . treatment discontinuation is mandatory if such intolerance occurs ; ii ) intoxication resulting in fever , cough , skin rash , polyneuritis , hepatitis , cardiac , and renal signs . alternative treatments for kala - azar include sodium stibogluconate , amphotericin b , liposomal amphotericin b , pentamidine , and paromycin .

we report the case of a six - year - old brazilian girl referred for splenomegaly who first presented with fever , asthenia , and weight loss . geographical location , clinical exam , and blood laboratories suggested kala - azar . serology confirmed kala - azar diagnosis , but direct evidence of the parasites was not made . a treatment by meglumine antimoniate is given under hospital surveillance for two weeks . thereupon , the patient is asymptomatic and all tests are normal .

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a 53-year - old african man was diagnosed with unknown primary undifferentiated carcinoma with mediastinal lymph nodes and thrombosis of superior vena cava in 1993 . the patient was initially treated by 8 cycles of chop ( cyclophosphamide , adriamycin , vincristine , and prednisone ) . he relapsed in 1996 with spinal bone metastases treated by laminectomy , radiotherapy and pfl - vp16 ( cddp , 5fu , leucovorin , etoposide ) . in 1999 he relapsed again with mediastinal lymph nodes treated by 3 cycles of navelbine and cisplatin followed by 3 cycles of carboplatin and navelbine with > 70% treatment response . biopsy at that time revealed large - cell carcinoma of bronchial or thymic origin . in 2002 newly discovered bone , pulmonary and mediastinal metastases were treated successively with taxotere / gemcitabine ( 6 cycles ) , navelbine / xeloda ( 6 cycles ) , iressa ( 6 months ) and tarceva ( 8 months ) . in 2005 , pemetrexed was maintained for only 4 cycles , then was suspended due to hematoxicity despite clinical efficiency . no maintenance treatment was used until april 2007 , when new bone metastases were discovered . the patient was hence treated with pemetrexed , as it once showed its efficacy in 2005 . after the sixth cycle , laboratory examination revealed serum creatinine 400 mol / l , metabolic acidosis ( plasma bicarbonate 21 mmol / l ) , sodium 145 mmol / l , potassium 4,5 mmol / l , urea 21 mmol / l . a 24-h urine collection on the 2nd hospital day revealed a 0.55 g proteinuria without hematuria or leukocyturia . a kidney biopsy was performed showing acute tubular necrosis ( atn ) associated with chronic interstitial fibrosis ( fig . his current renal function remained stable after 6 months follow - up of the acute renal failure ( arf ) episode with a stable serum creatinine level of 380 mol / l . our patient experienced severe acute kidney injury related to atn and interstitial fibrosis following sequential treatment with pemetrexed for a metastatic undifferentiated carcinoma . only few cases of arf due to pemetrexed have been reported . in a patient treated for metastatic non - small cell lung cancer , arf was associated with nephrogenic diabetes insipidus and distal renal tubular acidosis following 3 doses of pemetrexed ( 500 mg / m ) . at discharge 1 month after admission , the patient still demonstrated polyuria , hypokalemia , and metabolic acidosis despite recovery to a creatinine level of 1.7 mg / dl . in a second patient with unresectable pleural mesothelioma , pemetrexed ( 500 mg / m ) and cisplatin ( 75 mg / m ) for 3 cycles , then pemetrexed as a single agent induced arf appearing at the sixth cycle of pemetrexed . eighteen cases of renal failure during clinical trials of pemetrexed have also been reported . in the phase i pemetrexed maintenance therapy ( pmt ) study evaluating toxicity as primary end point , 8% of patients with malignant pleural mesothelioma treated with high doses ( 700 mg / m ) of pemetrexed experienced reversible grade 1 or 2 renal failure : creatinine clearance decreased from 88 21 ml / min at the end of the induction therapy to 77 26 ml / min at the end of maintenance therapy ( p < 0.05 ) . no grade 4 toxicity was observed . in phase iii trials , all grades of renal failure and grade 4 requiring dialysis were reported in 2.4 and 0.6% of patients , respectively . in all studies , baseline creatinine clearance ( estimated using the cockcroft - gault formula ) indeed , pemetrexed - induced renal toxicity may potentiate an enhanced myelosuppressive response to pemetrexed . in an initial phase i study the development of severe toxicity appeared to correlate most strongly with baseline renal function . patients with an estimated creatinine clearance value less than 80 ml / min were more likely to develop severe myelosuppression ( grade iv neutropenia ) than those with a creatinine clearance more than 80 ml / min . this suggests that initial dosing should be based on the area under the curve as currently utilized for carboplatin rather than on body surface area and renal function . this idea was confirmed by an analysis of 10 phase ii clinical trials . in a phase i dose escalation trial including patients with various degrees of renal dysfunction , pemetrexed seems to be well tolerated at doses of 500 mg / m with vitamin supplementation in the case of creatinine clearance = 40 ml / min . the fda even recommends a creatinine clearance of greater than 45 ml / min as the threshold for administering the drug . an experimental study demonstrated that in kidney proximal tubule , the folic acid is reabsorbed via renal folate receptors and brush - border membrane vesicles . the hypothesis is that the antifolate , like the folic acid , would be less reabsorbed by urine alkalinisation and increasing urine flow rate by hydration . on the other hand , thymidine is described as an antidote for pemetrexed - related toxicity in a clinical report , though in that report the concomitant use of hemodialysis complicates the interpretation of this favorable outcome . in summary ,

we report a patient with unknown primary undifferentiated carcinoma who developed acute renal failure associated with interstitial fibrosis following pemetrexed therapy . despite drug withdrawal , renal function remained altered and the patient experienced chronic renal insufficiency . pemetrexed disodium ( alimta ) is a multitargeted antifolate agent approved by the food and drug administration ( fda ) for patients diagnosed with mesothelioma and non - small cell lung cancer . this drug is almost exclusively cleared by renal excretion [ 1 ] . the most common side effects are hematologic dose - limiting toxicities and nonhematologic toxicities including fatigue , diarrhea , nausea , mucositis and rash . although few cases of renal failure have been published , no study has reported on the renal pathological findings in this setting . we present a case of acute tubular necrosis associated with interstitial fibrosis after pemetrexed therapy .

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acquired platelet dysfunction with eosinophilia ( apde ) is usually a self - limiting bleeding disorder characterized by an insidious onset of easy bruising with petechiae in an otherwise well person . hypereosinophilia is often the first clue to diagnosis , which is supported by the findings of a platelet storage pool disorder . apde has been mainly reported from thailand , malaysia , and singapore , but its true incidence has not been studied . the condition has rarely been reported elsewhere and hence travelers returning from an endemic area may present with a diagnostic challenge . an 11-year - old caucasian boy presented with recurrent cutaneous bruises and ecchymosis for five months . the child 's past health was only remarkable for occasional asthmatic attacks when he was small and he had no prior history of bleeding tendency or excessive swelling following vaccinations . fifteen months ago , the family moved from the united states and lived in central java , indonesia . five months before the consultation , he was noticed to have recurrent , unprovoked bruising of the skin with occasional epistaxis and gum bleeding . there were no symptoms of gastrointestinal , genitourinary , or intra - articular hemorrhage . he had not been noted to have worms in the stool although he had been treated with antihelminthics every 3 to 4 months . the child was otherwise well and continued to go to school as usual . on examination , there were multiple bruises from 1 to 3 cm in maximum dimension with petechiae over the limbs , the scalp , the chest and abdominal wall . laboratory investigations showed hemoglobin 12.8 g / dl , white cell count 14.810/l , eosinophils 7.410/l , platelet 22310/l , ige > 2,000 iu / ml serum biochemistries , liver transaminases , prothrombin time , partial thromboplastin time , and other immunoglobulin levels were normal . the peripheral blood film shows prominent eosinophilia with the presence of gray platelets ( figure 1 ) . the results of the platelet aggregation tests showed defective aggregation with collagen and epinephrine , consistent with a platelet storage pool disorder ( table 1 ) . figure 1photomicrograph of the blood film ( 100 ) showing an eosinophil of normal morphology ( eo ) , a platelet of normal morphology ( p ) , and platelets that appear pale and agranular ( arrows ) . the latter feature is highly suggestive of thrombocytopathy and should obviate the need to measure the bleeding time . photomicrograph of the blood film ( 100 ) showing an eosinophil of normal morphology ( eo ) , a platelet of normal morphology ( p ) , and platelets that appear pale and agranular ( arrows ) . the latter feature is highly suggestive of thrombocytopathy and should obviate the need to measure the bleeding time . table 1the results of the patient 's platelet aggregation tests.testresultnormal rangesadp69%64111%collage31%68117%epinephrine21%46122%ristocetin100%80115%arachidonic acid78%52110% he was empirically treated with albendazole 400 mg as single dose and a repeated dose two weeks later . the absolute eosinophil counts fell to 0.67 and 0.6310/l one and four months afterwards , respectively . acquired platelet dysfunction with eosinophilia ( apde ) is a unique disease that was first and almost exclusively described in the region of thailand , malaysia and singapore . the condition affects mainly patients of the pediatric age group , but adults are not spared . helminthic infestation has been associated with apde in about 50% of the cases , but how helminthes would explain the geographic occurrence is mysterious . the thrombocytopathic bleeding is evidenced by a prolonged bleeding time and positive hess 's test , degranulated platelets , and abnormal platelet aggregation tests consistent with a platelet storage pool disorder . the platelet dysfunction is believed to be secondary to eosinophilia but raised eosinophil counts are not found in all patients . reported from thailand a large cohort of 168 children diagnosed with apde . the majority of them presented with mild cutaneous bruises only , but 14 ( 8% ) of them had severe bleeding symptoms that necessitated platelet transfusion therapy . the bleeding manifestations resolved within 6 months of diagnosis , although 12 ( 7% ) of them had a recurrence . five of them recovered within two months after anti - helminthic treatment while the bleeding manifestations persisted for 36 months in the other patient . in particular , the presence of multiple bruises in the presence of normal platelet count and coagulation screen may be confused with accidental or non - accidental injury , while the extreme hypereosinophilia may be suggestive of hypereosinophilic syndrome . a comprehensive review by a pediatric hematologist will be essential for an accurate diagnosis without embarking on distressing medical or social investigations . as the case has illustrated , the diagnosis of apde can be reasonably reached with attention to the history , physical findings , simple laboratory tests , and examination of the platelet morphology on blood smear . sporadic reports from the united kingdom , canada , and hong kong are usually imported cases from the southeast asia ( table 2 ) . all five children presented with easy bruising , eosinophilia with normal platelet counts , but parasites were not found in any of them . some of these patients had been extensively investigated before the diagnosis of apde was made . together with this reports , the present case is illustrative of the fact that apde is not restricted to the indigenous population in the tropical countries and it may affect any child who has traveled to the southeast asia . table 2pediatric cases of acquired platelet dysfunction with eosinophilia reported from non - tropical countries.casessex/age ( year)reporting countriescountries traveledparasitology / recoveryref1female/8united kingdommalaysiano parasite foundrecovered in 3 months112male/5canadamalaysiano parasite foundrecovered in 1 month123male/6canadamalaysiano parasite foundrecovered in 2 months124male/4hong kongthailandno parasite foundrecovered in 1 month135female/8hong kongnepalno parasite foundrecovered in 1 month13

an 11-year - old american boy was staying with his family in indonesia . he presented with a 5-month history of recurrent bruises and ecchymosis . a clinical diagnosis of acquired platelet dysfunction with eosinophilia was made when his full blood counts showed hypereosinophilia ( 7.4109/l ) with normal platelet count and gray platelets under the microscope . the diagnosis was supported by abnormal platelet aggregation tests consistent with a storage pool disorder . the bleeding symptoms and eosinophilia resolved a month later with a full course of antihelminthic therapy . hematologists should be aware of this unusual disease in travelers returning from the southeast asia .

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surgical aortic valve replacement ( avr ) still represents the gold standard among the therapeutic options in patients with severe symptomatic aortic valve stenosis . currently , patients often have a heavily calcified valve , aortic root or diffuse atherosclerosis of the aortic wall and have already undergone a previous aortic valve replacement . in order to minimize periprocedural risks and to accelerate postoperative rehabilitation , less invasive therapeutic concepts , including transcatheter aortic valve implantation ( tavi ) and sutureless bioprosthesis , have been developed and are increasingly used while maintaining quality and safety , especially in gray zone patients . the need for concomitant mitral valve surgery is generally viewed as a contraindication to sutureless avr because of the increased risk of interference between the two valves at the level of aorto - mitral continuity . we present the case of a 71-year - old female patient with a combination of severe stenosis of the stentless bioprosthesis and regurgitation grade ii / iv due to right coronary cusp separation . the peak transvalvular gradient was 56 mm hg and the mean gradient was 30 mm hg . concomitant severe mitral valve insufficiency grade iv / iv was present due to annulus dilatation . the ascending aorta and bicaval cannulation technique was used for initiating the cardiopulmonary bypass ( cpb ) . a transverse aortotomy was done 1 cm distal to the sino - tubular junction , so as to leave an edge free for closure of the aortotomy after implantation of the device and to prevent closure of the aortotomy . because of a very small aortic annulus ( free passage through the annulus with a 19 mm mechanical aortic valve sizer ) , the perceval s ( sorin group , milan , italy ) size small s access to the mitral valve was performed through sondergaard s groove , and mitral valve repair was performed with a semi - rigid medtronic cg future composite ring no . the selected aortic bioprosthesis perceval s was loaded and collapsed into a delivery device . to ensure correct positioning of the prosthesis , three guiding threads are temporarily positioned in the lowest part of the native leaflet insertion line for each valve sinus and the corresponding part of the bioprosthesis . once the prosthesis was completely deployed , the guiding threads were removed . to optimize the area of contact between the prosthesis and the aortic annulus , post - dilatation was carried out with a balloon catheter at a pressure of 4 atm for 30 s. the aortic cross clamp time was 74 min . the control periprocedural transesophageal echocardiogram did not indicate any paravalvular aortic regurgitation ; there was no evidence of interference between the aortic prosthesis and mitral valve ring and no evidence of mitral dysfunction . at 1-year follow - up the patient was doing well , was in nyha class 0 and showed improved symptoms in comparison with her preoperative state . transthoracic echocardiography ( tte ) follow - up indicated mean and peak gradients of 15 and 25 mm hg on the perceval valve and no paravalvular regurgitation . the mean mitral transvalvular gradient was 4 mm hg and mitral regurgitation grade i / iv was detected by tte . similar to conventional surgical replacement of the valve , a sutureless bioprosthesis requires valve excision ( a risk reduction of paravalvular insufficiency compared with tavi ) and annular decalcification , but permanent fixation sutures are not required . the perceval valve is designed for patients requiring an avr procedure , including high - risk and complex patients . with the absence of a rigid sewing ring and its elastic stent , the perceval optimizes the effective orifice area , resulting in excellent hemodynamics . the possibility to avoid placing and tying sutures may lead to shorter procedural times [ 2 , 4 ] . in cardiac surgery , prolonged cpb and cross - clamp duration are strong independent risk factors for postoperative mortality and morbidity . the advantages of this procedure could be of benefit to patients who have no fundamental contraindications for using cardiopulmonary bypass and are undergoing complex , combined procedures or re - operations . patients with a small aortic annulus or heavy calcification of the annulus and aortic root , where positioning sutures may represent technical problems and complications , are another potential group that could benefit . it is important to accept some technical considerations that arise in the proximity of the mitral and aortic annulus at the level of aorto - mitral continuity . the cut - off point in terms of minimal aorto - mitral length for patients with a mechanical mitral prosthesis before tavi is 9 mm and is probably lower for sutureless avr , such as the perceval prosthesis [ 3 , 6 ] . in our patient we did not measure the aorto - mitral distance . at the time of mitral valve replacement , the commissural struts could be positioned away from the aortomitral continuity to minimize the risk of interference with the intra - annular portion of the sutureless aortic prosthesis . for mitral valve repair our preferred approach is the use of a semi - rigid mitral annuloplasty ring , which offers posterior remodeling while maintaining anterior flexibility due to the presence of only textile in this part and may also minimize the risk of interference with the subannular portion of the sutureless valve in the left ventricle outflow tract . our experience demonstrates that concomitant sutureless aortic bioprosthesis implantation and mitral valve repair is feasible and safe in high - risk patients undergoing a redo operation . potential advantages include shorter aortic cross clamp times , fewer technical demands in the case of a heavily calcified and small aortic annulus , and the preservation of flexibility and movement of the mitral annulus during the cardiac cycle by using a semi - rigid annuloplasty ring .

sutureless aortic valve replacement ( avr ) was developed as an alternative treatment option to conventional open - heart surgery and transcatheter aortic valve implantation for gray zone patients . the need for concurrent mitral valve surgery is generally viewed as a contraindication to sutureless avr . the purpose of this brief paper is to report our experiences with sutureless valves in patients after previous cardiac procedures with degenerated aortic bioprostheses and concomitant mitral valve disease .

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99mtc pertechnetate scintigraphy is routinely used to detect testicular torsion and differentiate this condition from acute epididymo - orchitis . however , differentiation of torsion from hydrocele and testicular or scrotal abscess may be difficult . in this report , we present a 5-year old child in whom epididymitis with hydrocele was misdiagnosed as testicular torsion on scrotal scintigraphy . a 5-year - old boy presented to the pediatric emergency department with a complaint of left scrotal swelling and local tenderness for 7 h. doppler ultrasound ( us ) imaging showed mild hydrocele of the left scrotum with no e / o torsion of the left testis . static images at 5 and 10 min showed a halo - like pooling of tracer in the periphery of the left hemi - scrotum with a photopenic center and normal tracer uptake in the right hemi - scrotum [ figure 1 ] . a scintigraphic diagnosis of mid - phase testicular torsion of the left testis was made and the patient was immediately operated . however , it was discovered intraoperatively that the patient had epididymitis with a hydrocele and not torsion of the left testis . static images at 5 and 10 min show a halo - like pooling of tracer in the periphery of the left hemi - scrotum ( arrow ) with a photopenic centre . normal tracer uptake is seen in the right hemi - scrotum differentiation by scintigraphy between acute torsion , hydrocele , testicular or scrotal abscess , or even inguinal hernia can be difficult , and images must be interpreted in conjunction with clinical findings from scrotal transillumination . in this situation , sonography can provide useful complementary information.[14 ] in a previous study comparing scintigraphy and us in children with scrotal pain , doppler us was able to provide the diagnosis of epididymo - orchitis in cases of false - positive scintigraphy . a peri - testicular hyperemic rim on radionuclide scrotal scintigraphy epididymitis and hydrocele have also been reported to mimic testicular torsion on scintigraphy in adults.[68 ] the present study describes a halo - like appearance on scrotal scintigraphy caused by epididymitis with co - existing hydrocele in a clinical setting , suggestive of testicular torsion in a child .

scintigraphic differentiation between acute torsion , hydrocele and testicular or scrotal abscess can be difficult . doppler sonography may provide useful complimentary information toward diagnosis . the authors describe a 5-year - old child where epididymitis with hydrocele was misdiagnosed as testicular torsion on scrotal scintigraphy .

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nemazee had been studying the deletion of autoreactive b cells in transgenic mice whose b cells all expressed receptors specific for a particular mhc molecule . when this transgene was bred onto mice that expressed that mhc protein , as expected , these mice lacked autoreactive b cells in the periphery . but to nemazee 's surprise , a large pool of autoreactive b cells persisted in the bone marrow ( 3 ) . to pinpoint the exact step at which the cells were escaping deletion , nemazee and his team engineered strains in which the autoantigen was targeted to different anatomical locations . expression of autoantigen in just the liver caused a near complete deletion of anti - mhc b cells , which were not replaced by non - autoreactive counterparts . but when autoantigen was also present in the bone marrow , there were many more peripheral b cells that were no longer self - reactive . nemazee discovered that these cells had escaped by switching antibody receptors they had new light chains derived from a rearranged version of the endogenous gene . the alterations took place in immature b cells , as nemazee only detected the rearrangements in bone marrow b cells . light chain replacement was simultaneously demonstrated in a different transgenic model by martin weigert and his team at the fox chase cancer center ( philadelphia , pa ) . while studying lupus , weigert had designed mice that carried a transgene for an anti - dna antibody . younger mice had fewer b cells , suggesting that autoreactive clones had been deleted . but adult mice had normal numbers of b cells . weigert and nemazee published their seminal results in a series of papers in the journal of experimental medicine in 1993 ( 46 ) . the studies were at first controversial , but numerous reports from other groups have since bolstered the case for receptor editing as a major mechanism for tolerance ( 7 ) . it is now estimated that at least 25% of b cells in the repertoire have undergone receptor editing ( 8) . nemazee 's anti - mhc transgenic mouse model has since been modified such that transgenes insert specifically into the heavy and light chain loci ( 9 ) . repairing its receptors rather than throwing away the whole cell might be the most efficient way to generate a diverse , non - self - reactive repertoire .

in 1993 , david nemazee and martin weigert independently showed that autoreactive b cells could proofread , alter , and reexpress modified receptors to become nonautoreactive . this process , called receptor editing , has since gained prominence as the main mechanism of b cell tolerance .

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traditionally , the neisseria species has two potential pathogenic strains ; neisseria meningitidis and neisseria gonorrhoeae . the remainder of neisseria species , including neisseria mucosa , are considered normal flora colonizing the respiratory tract , living in symbiosis . one analysis showed that the majority of people are colonized by one to two of these neisseria species . specifically , neisseria mucosa is increasingly found to cause a multitude of diseases , in particular peritonitis . part of the difficulty in associating disease with other species of neisseria , such as neisseria mucosa , is the fact that they do not contain the typical virulence factors . the established pathogens neisseria meningitidis and neisseria gonorrhoeae derive much of their virulence from attaching to mucosal surfaces . however , the lack of these virulence factors does not necessarily make the other neisseria species benign . the advent of chronic ambulatory peritoneal dialysis ( capd ) has permitted significant patient autonomy with the concomitant risk of bacterial peritonitis . the typical culprits are gram - positive species , such as staphylococcus species and streptococcus species . we performed a pubmed literature search using the terms neisseria mucosa , peritonitis , and chronic ambulatory peritoneal dialysis . this yielded very few published cases of capd patients afflicted by neisseria mucosa peritonitis . in this clinical vignette , we add another case of capd associated with neisseria mucosa peritonitis . the patient was a 28 year - old hispanic man with a history of end stage renal disease due to hypertensive disease since the age of 10 years , complicated by malignant hypertension . his surgical history was remarkable for a remotely failed renal transplant requiring an allograft nephrectomy . he had been on hemodialysis for about a decade since , and transitioned to peritoneal dialysis just six months prior to presenting to our facility with sepsis due to new - onset peritonitis . in the outpatient clinic , the patient had been diagnosed with external cheek cellulitis that responded to a short course of empiric cephalexin . he overcame this only to experience three days of abdominal pain near his dialysis catheter . the pain was constant and severe pain , worsened by draining and filling during dialysis sessions . he denied any fevers , chills , nausea , vomiting , diarrhea , oropharyngeal and genitourinary complaints or decrease in recent ultrafiltration . exam was remarkable for a blood pressure of 167/99 mmhg , heart rate of 107 beats per minute and abdominal tenderness to palpation diffusely with the catheter exit site clear dry and intact without exudate or erythema . he quickly underwent peritoneal fluid examination , revealing an absolute neutrophil count of 14,458 cells / mm , confirming the diagnosis of bacterial peritonitis . his gram stain revealed gram - negative diplococci and subsequent chocolate agar plated cultures grew neisseria species , not gonorrhoeae or meningitidis . further biochemical speciation ( via rapid nh system by remel , thermo fisher scientific inc . , waltham , usa ) showed neisseria mucosa to be the etiology of the patient s bacterial peritonitis . given this is typically nonpathogenic , further susceptibility was not performed . the patient was placed on empiric intraperitoneal vancomycin 1 gram and cefepime 1 gram therapy and later transitioned to oral ciprofloxacin 500 mg daily for two weeks . during the hospitalization , the likely source of neisseria mucosa contamination of the dialysis port was the oral cellulitis . the transmission from the oral site to catheter site is supported by the well - known colonization of the oropharyngeal tract . capd seems to be associated with an increased risk for neisseria mucosa , particularly in cases of peritonitis . in general , this case adds to the current literature highlighting the importance of considering all types of disease caused by traditionally - benign neisseria mucosa species . although , nongonococcal and nonmeningococcal neisseria strains are usually benign and infections are rare , they may cause a variety of disease . this case highlights the danger of neisseria mucosa peritonitis in patients undergoing capd , and is the fourth reported case . the rarity of case reports and lack of the established pathogenic factors of nongonococcal and nonmeningococcal neisseria may limit recognition of these infections . this makes the association with clinical disease complex , and further investigation regarding their pathogenicity is warranted . in previously described case reports of nongonococcal and nonmeningococcal neisseria , our patient was also successfully treated with ciprofloxacin . given the increasing frequency of infections by nongonococcal and nonmeningococcal neisseria , guidelines regarding appropriate antimicrobial therapy should be established . further case reports should also establish the safety of preserving the peritoneal dialysis catheters , as in our patient s case .

peritonitis is a leading complication of chronic ambulatory peritoneal dialysis . however , very rarely does neisseria mucosa cause peritonitis . we describe an unusual case of n. mucosa peritonitis in a chronic ambulatory peritoneal dialysis patient . a 28-year - old hispanic male presents with diffuse abdominal pain exacerbated during draining of the peritoneal fluid . peritoneal fluid examination was remarkable for leukocytosis and gramnegative diplococci . bacterial cultures were positive for n. mucosa growth . the patient was treated with ciprofloxacin with preservation of the dialysis catheter . this case highlights the rarity and importance of neisseria mucosa causing peritonitis in chronic ambulatory peritoneal dialysis patients. there seems to be a unique association between n. mucosa peritonitis and chronic ambulatory peritoneal dialysis patients. the patient was successfully managed with ciprofloxacin along with salvaging of the dialysis catheter .

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duodenal atresia and stenosis are rare causes of intestinal obstruction in the newborn , with a prevalence of 1 in 5,000 to 10,000 live births , with duodenal stenosis occurring less frequently than duodenal atresia.1 however , these intestinal tract anomalies occur significantly more frequently in patients with down syndrome . approximately 2.5% of infants with down syndrome are ultimately diagnosed with either duodenal atresia or stenosis.2 conversely , 24% of patients with duodenal atresia or stenosis carry a diagnosis of down syndrome.3 duodenal atresia invariably presents within the first few hours to days of life with persistent vomiting after all feeds . in general , the atresia occurs at the level of , or just distal to , the ampulla of vater.4 as a consequence , the emesis is frequently bilious and quickly brought to the attention of the medical provider . on the other hand , recurrent episodes of vomiting and failure to thrive are the most common presenting symptoms of duodenal stenosis.5 we report this case because of its unusual and delayed presentation despite the presence of high - grade stenosis . moreover , few endoscopic images of duodenal stenosis have been published in the literature , suggesting that this finding is uncommon , but providers need to be prepared to encounter this complication . a 5-month - old male infant with down syndrome presented to the emergency department with coffee - ground emesis . two weeks before admission , the patient had a single episode of emesis with dark streaks concerning for blood . he looked well on examination by his pediatrician and was started on lansoprazole with the plan to follow - up at our pediatric gastroenterology clinic . however , coffee - ground emesis recurred , and the infant was referred to the emergency department for evaluation . growth had been appropriate for a child with down syndrome . at the time of the emergency room evaluation , abdominal radiography showed a normal bowel gas pattern . on the day of admission , the patient underwent esophagogastroduodenoscopy using a gif - xp 160 endoscope ( olympus , tokyo , japan ) . there was mild erythema in the distal esophagus , and a dark brown substance was observed in the stomach , consistent with blood exposed to gastric secretions . 1a ) , with a tubular structure containing normal - appearing villous mucosa in the center ( fig . 1b ) . no lumen could be identified in this structure . an upper gastrointestinal series ( fig . 2 ) demonstrated a markedly dilated duodenal bulb and narrowing of the second portion of the duodenum ( arrows ) , confirming the suspicion of duodenal stenosis . intestinal malrotation was also identified at the time of surgery ; and therefore , the patient underwent ladd 's procedure . duodenal stenosis frequently presents with recurrent vomiting and failure to thrive . owing to its chronic and variable presentation it has been reported that the presentation and diagnosis of duodenal stenosis may be delayed to as late as adolescence.6 therefore , pediatric providers should maintain a high index of suspicion for duodenal stenosis , particularly in patients with down syndrome . our patient presented at the age of 5 months , outside of the immediate neonatal period , and with the atypical presenting sign of hematemesis . however , other studies have reported that hematemesis is the primary presenting symptom of duodenal stenosis and atresia in children.7,8 the etiology of hematemesis in these patients is not clear but may be related to esophageal or gastric irritation in the setting of gastric stasis , recurrent reflux , and vomiting . hematemesis has been better described in pyloric stenosis and is secondary to reflux esophagitis in these patients.9 the mechanism of duodenal stenosis may be similar . our patient showed erythema in the distal esophagus and had no evidence of duodenitis ; therefore , esophagitis was considered to be the most likely cause of bleeding . a typical finding of duodenal atresia on abdominal radiography in infants is the " double bubble " sign , which is marked gaseous distention of the proximal duodenum and stomach . duodenal stenosis is classically diagnosed by an upper gastrointestinal series , which demonstrates a dilated stomach and duodenal bulb and a narrowing in the duodenum at the location of stenosis.4 an upper gastrointestinal series was not used as the initial diagnostic modality in our patient because he reported hematemesis without a history of chronic vomiting as the primary presenting sign . diagnosis by endoscopy is unusual , and few endoscopic images of congenital duodenal stenosis have been published in the literature so far . once medically stable , the patients can undergo operative repair with duodenoduodenostomy performed with either side - to - side or diamond - shaped anastomosis . our patient underwent a diamond - shaped duodenoduodenostomy , which allows earlier postoperative feeding and a shorter hospital stay and is therefore the preferred procedure.10 in conclusion , patients with down syndrome are at a higher risk of gastrointestinal anomalies . even high - grade duodenal stenosis can present late and atypically in children , as observed in our patient with hematemesis at 5 months of age . therefore , pediatric gastroenterologists should maintain a high index of suspicion for congenital duodenal stenosis in older infants and children and should be familiar with the endoscopic appearance of this lesion .

duodenal stenosis and duodenal atresia are well - known gastrointestinal anomalies in patients with down syndrome . although duodenal atresia presents early and classically with vomiting in the immediate neonatal period , the presentation of duodenal stenosis can be significantly more subtle and the diagnosis delayed . here , we describe the case of a 5-month - old male infant with down syndrome and delayed presentation of high - grade duodenal stenosis diagnosed endoscopically . pediatric gastroenterologists should include duodenal stenosis in the differential diagnosis of older infants and children with vomiting and should be familiar with the endoscopic appearance of this lesion .

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among stage iiia non - small cell lung cancer patients , t4n0 - 1 cases can be good candidates for surgery and have a relatively favorable postoperative prognosis [ 1 , 2 ] . however , most t4 cases with thoracic vertebral invasion may not be operated as complete resection with vertebrectomy is challenging . we report the case of a male patient with primary lung pleomorphic carcinoma invading the thoracic vertebra who underwent complete resection with en bloc total vertebrectomy after embolization of the tumor - feeding vessels . a 35-year - old japanese man presented with a 6-month history of left back pain . chest x - ray and ct revealed that a tumor ( 43 34 mm ) in s1 + 2 of the left lung had invaded the third thoracic vertebra ( fig . an mri revealed that the tumor had invaded the third thoracic vertebra and the third rib ( fig . 1c ) . as no nodal or distant metastasis was identified by whole - body ct and bone scintigram , we planned a primary surgery with a clinical diagnosis of lung cancer invading thoracic vertebrae ( ct4n0m0 , stage iiia ) . to prevent massive bleeding during resection of the tumor with vertebral invasion , arterial embolization was performed prior to surgery , and the first , second , and third intercostal arteries feeding the tumor ( fig . we performed a complete resection consisting of left upper lobe lobectomy and lymph node resection ( nd2a-2 ) , partial resection of the second and third ribs , and total en bloc spondylectomy of the third thoracic vertebra . pathological examination showed that all resection margins were free from malignant cells , and the final pathological diagnosis was pleomorphic carcinoma of the lung ( pt4n0m0 , stage iiia ) . we conducted 3 cycles of adjuvant chemotherapy ( cisplatin , 80 mg / m ; docetaxel , 60 mg / m ) followed by oral administration of s-1 [ 4 , 5 ] and radiation to the primary tumor field . the patient is alive at 14 months after surgery and without any evidence of tumor recurrence . patients with primary lung cancer invading the vertebral column are rarely operated [ 6 , 7 ] as the postoperative survival is poor ( 5-year survival rates , 1620% ) [ 6 , 8 ] . however , when complete resection is achieved , favorable prognosis might be expected for such patients [ 6 , 7 ] . thus , complete resection with vertebrectomy , especially total vertebrectomy , is challenging in the field of lung cancer surgery . in the present case , we adopted surgical treatment for the following reasons : ( 1 ) no nodal or distant metastasis was identified by whole - body ct and bone scintigram , and ( 2 ) complete en bloc tumor resection can be expected by total vertebrectomy of the third thoracic vertebra . prior to surgery , we performed embolization of the tumor - feeding arteries to prevent possible uncontrollable bleeding during vertebretcomy . we performed surgery first because complete resection is expected by this technique without preoperative induction therapy . in addition , life - threatening or extremely unpleasant spinal cord invasion and/or meningitis may occur when chemoradiation therapy does not result in tumor shrinkage . accordingly , we conducted adjuvant chemotherapy and radiation after surgery . as summarized , a careful preoperative evaluation is essential to determine surgical indication , surgical approach , and sequence of multimodality therapy for t4 tumor with vertebral invasion .

we present a case who had left upper lobectomy with total vertebrectomy after arterial embolization in preparation for intraoperative bleeding . a 35-year - old man complained of left back pain . chest ct revealed a tumor in s1 + 2 of the left lung , invading the third thoracic vertebra . as no nodal or distant metastasis was detected , we performed left upper lobectomy and lymph node dissection ( nd2a-2 ) after embolization of the vessels feeding the tumor in order to reduce intraoperative bleeding . in addition , the team of orthopedics performed en bloc resection of the third thoracic vertebra and parts of the left third and fourth ribs . histological examination of the tumor revealed pleomorphic carcinoma ( pt4n0m0 , stage iiia ) .

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although priapism has been reported as a complication of malignant tumor metastasis , leukemia , sickle cell disease , embolism and spinal canal stenosis [ 1 , 2 , 3 , 4 , 5 ] , there are few reports of priapism as a complication of colorectal cancer in the absence of penile metastasis . here we report a patient with rectal cancer with no penile metastasis in whom chemotherapy resulted in an improvement of priapism . a 65-year - old man was admitted to our hospital for priapism with tenderness of the penis and dysuria . enhanced abdominal computed tomography demonstrated metastatic tumors in the liver , lung , sacrum ( fig . ultrasonography of the penis revealed no tumor and normal blood flow in the penis vessel . chemotherapy ( folfox4 ; levofolinate 25 mg , fluorouracil 250 mg , oxaliplatin 100 mg ) was administered , and although the primary rectal cancer showed no change ( fig . brain or splenic metastasis and hypercalcemia arising from bone metastasis have been reported as rare complications of colorectal cancer [ 6 , 7 , 8 ] . chemotherapy regimens for metastatic colorectal cancer include fluorouracil , leucovorin , either oxaliplatin or irinotecan , and the vegf inhibitor bevacizumab . priapism is a complex involuntary behavioral response that depends on the integration of vascular , endocrine and neurological mechanisms . stimuli for erection can be classified as psychogenic and reflexogenic . when visceral nerves at the sacrum are stimulated electrically , this results in persistent penile erection . nervi erigentes. a second , thoracolumbar erection centre at the level of t12l1 plays a role in psychogenically mediated erections via sympathetic efferent fibers . disturbances in penile blood flow due to metastasis in the penis have been reported to cause priapism . in this case , the cause of priapism might have been micrometastasis in the penis , metastatic tumors that affected the spinal cord , or continuous stimulation of nervi erigentes by a metastatic tumor . chemotherapy , which reduced the metastatic tumor in the sacrum , may also have reduced the level of nervi erigentes stimulation . the results from this case suggest that chemotherapy can be effective for treating rare complications of rectal cancer such as priapism .

a 65-year - old man was admitted with penile tenderness and dysuria due to priapism . enhanced computed tomography revealed metastatic tumors in the liver , lung , sacrum and lymph nodes . advanced rectal cancer , detected by colonoscopy as a primary tumor , was treated with chemotherapy ( folfox4 ) . although the rectal cancer showed no change , five months of chemotherapy improveid the priapism , suggesting that chemotherapy can improve rare symptoms of rectal cancer .

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acromegaly is a syndrome seen in adults due to excessive production of pituitary growth hormone as a result of an adenoma or hyperplasia of the eosinophilic cells of the anterior pituitary gland . the main clinical features of acromegaly are skeletal overgrowth affecting the hands , feet , and skull along with spinal deformities like kyphosis . the interface between psychiatry and endocrinology is well documented and psychiatric problems in various endocrine disorders are well known . psychiatric issues in acromegaly have been addressed sparsely and no systematic studies exist for the same , though anecdotal case reports are present in literature . one case depicts pure depression with acromegaly , while another reports the presence of depression with pathological gambling . other psychiatric symptoms like schneiderian first - rank psychotic symptoms , persecutory delusions , visual and auditory hallucinations , apathy with lack of motivation and mood swings have all been documented in acromegaly . in all the cases , response to various medications used has been excellent bringing about a reduction of symptoms . one study on 12 patients with acromegaly failed to prove a relationship between psychopathology and growth hormone levels , while it did mention a sexual dichotomy with 11 patients being female . a 33-year - old lady from middle socioeconomic class presented with depressed mood , loss of appetite , lack of sleep at night , inability to concentrate on her day - to - day activities , and occasional passive suicidal themes in her thoughts . the patient had a similar episode three years ago and had responded well to sertraline . the patient 's father had a history of depression with psychotic features and during his hallucinatory episodes had committed suicide by jumping into a well . the facial features noted by us were prognathia of the mandible , enlargement of the supro - orbital ridges , enlarged facies , and macroglossia . on testing after endocrine consultation , the patient had a high fasting blood sugar of 185 mg% while post lunch blood sugar was 210mg% . the level of growth hormone was 7.2 ng / ml ( normal 0.044.5 ng / ml ) . a ct scan revealed an enlarged sella tursica and a thickened skull with pituitary enlargement . the patient was started on escitalopram 10 mg / day with zolpidem 10 mg at night for depressive symptoms . the patient was also called weekly for cognitive therapy sessions where suicidal and negative thoughts would be addressed . the patient started responding showing a 20% improvement in the first week itself with 80% symptom reduction at the end of four weeks . the patient was to undergo treatment with the endocrinologist for acromegaly but was noncompliant and did not follow - up after the fifth week . during the five weeks of clinical observation , improvement was 80% with no worsening of acromegaly symptoms . it was difficult to label the depression secondary to her acromegaly as the endocrine features did not bother the patient and were detected by us . a strong family history of depression with psychotic features and suicide of her father may have contributed to her depression . our limited knowledge and lack of data on the relationship between depression and acromegaly makes it very difficult to comment on any associations .

depression is one of the commonest disorders encountered in general hospital psychiatry . acromegaly is a condition with excessive growth hormone secretion that may at times present with oversychopathology . we present the case of a 33-year - old lady with depression and acromegaly that successfully resolved after treatment with escitalopram and cognitive therapy .

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pancreatic endocrine tumors are classified , according to the symptomatology , in secreting and nonsecreting tumors . the nonsecreting tumors ( silent , in hormonal terms ) represent about 50% of the total ; they are followed by insulinomas - 25% and gastrinomas - 15% . it may be associated with other endocrine glands tumors in the multiple endocrine neoplasia type i ( men i ) ( parathyroid , pituitary , endocrine pancreas ) . the islet cell tumors are the most common cause of hypoglycemia resulting from endogenous hyperinsulinism . the median age at diagnosis is about 47 years , except in insulinoma patients with men 1 , in whom the median age is the mid-20 s . a 61-years old man known with hypertension and alcoholic steatohepatitis , presented on 26/03/2013 for syncopes , tonic - clonic seizures , sweating , anxiety . alcohol consumption had been stopped 2 months before the onset of the symptoms , according to the patient and his relatives statements . in the patient medical history we found an emergency admission on 20/02/2013 for psychomotor agitation , episodes of loss of consciousness with tonic - clonic seizures , delirium of mixed etiology ( alcohol and hypoglycemia ) , tremor of the upper limbs , sweating , disorientation in time and space , important hypoprosexia , fixing and evocation hypoamnesia , insomnia . blood tests evidenced 41 mg / dl hypoglicemia , hyperkaliemia , twice the normal values of lactate dehydrogenase ( ldh ) . the cranial computed tomography ( ct ) did not reveal any damage except an old ischemic millimetric lesion and a degree of atrophy . the patient was admitted to the diabetes , nutritional and metabolic diseases clinic for suspected insulinoma . the abdominal ct revealed no pathological changes in the abdominal organs , no lymph node changes . due to his agitation , seizures , and delirium , the symptoms were interpreted as alcohol withdrawal and he was transferred to the department of psychiatry . during hospitalization the blood glucose fasting levels were found again between 30 and 50 mg / dl . the neurologist interpreted the old ischemic lesion shown on the ct as possibly due to hypoxic damage caused by severe hypoglycemia . the patient was discharged with the diagnosis of complicated withdrawal seizures , chronic alcohol dependence , history of disabling ischemic stroke in the left carotid territory , with recommendation for hospitalization in a medical clinic . the following were determined : the c peptide , insulinemia and glycated hemoglobin , which were normal and did not support the diagnosis of insulinoma . , hypoglycemia was attributed to the alcohol consumption and the patient was released on 03/04/2013 . after a month , on 26/03/2013 , the patient came back for persistent symptoms . blood tests showed 39 to 59 mg / dl glucose levels and mixed dyslipidemia , carbohydrate antigen ( ca)19 - 9 was normal , the other analyses were normal . we decided to repeat the abdominal magnetic resonance imaging ( mri ) with contrast , and we discovered a 21 mm hypervascular tumor of the pancreatic uncinate process , suggesting , as first hypothesis , an endocrine tumor and peripancreatic millimetre lymph nodes . we transferred the patient to the surgery department , where the uncinate process tumor was excised and peripancreatic lymph nodes were biopsied . the histopathological appearance ( fig . 3 ) was positive in 56% of tumor cells ( nuclear expression ) , findings that were supporting the diagnosis of neuroendocrine tumor . based on the result of the histopathological examinations , corroborated with the imaging and intraoperative exploration , the tumor stage was as pt3n0mx . the rule of 10 states that 10% are multiple , 10% are malignant , insulinomas are associated with men 1 in 5% of patients and it is estimated that 21% of patients with men1 develop insulinomas . the incidence is 310 cases per million people per year . once surgically removed , the insulinomas occurring in this autosomal dominant syndrome have a higher risk of relapse . long - term survival of patients with insulinoma is generally excellent ; it is considered that approximately 9095% of insulinomas have benign histological behavior , so healing with dissaperance of symptomatology after complete resection is the rule . recurrences were observed in 5.4% of cases in a series of 120 patients with benign insulinomas , over a period of 417 years . in these cases long - term survival is possible in malignant insulinomas , especially in cases strictly localized to the pancreas and with good response to adjuvant chemotherapy ; median disease - free survival after curative resection is estimated at 5 years . the diagnosis of insulinoma often comes from a hunch , from the impossibility of highlighting the cause of repeated hypoglycemia in an apparently healthy patient . but for diagnostic certainty , patient follow - up and repeated analysis are necessary . proper management for timely treatment of a patient with insulinoma involves complex medical teamwork consisting of physicians from various specialties : endocrinology , internal medicine , surgery , pathology , medical imaging , oncology and , like in our case , psychiatry .

insulinoma is a rare pancreatic islet cell tumor , the most common cause of hypoglycemia related to endogenous hyperinsulinism . we present the case of an adult patient with pancreatic insulinoma . the patient presented to our clinic after prior hospitalizations in diabetes and psychiatry hospital units for repeated episodes of loss of consciousness , sweating and tonic - clonic seizures . early detection of the cause is important for prompt initiation of therapy and to reduce symptoms . we describe our diagnostic and therapeutic strategies with references to previously published reports .

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experimental details , xray crystal structure of culoaded f33y cubmb , malditof mass spectra , epr simulation , and extra uv / vis , epr spectra are provided in the supporting information . 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 .

abstractrational protein design has been proven to be a powerful tool for creating functional artificial proteins . although many artificial metalloproteins with a single active site have been successfully created , those with dual active sites in a single protein scaffold are still relatively rare . in this study , we rationally designed dual active sites in a single heme protein scaffold , myoglobin ( mb ) , by retaining the native heme site and creating a copperbinding site remotely through a single mutation of arg118 to his or met . isothermal titration calorimetry ( itc ) and electron paramagnetic resonance ( epr ) studies confirmed that a copperbinding site of [ 3his ] or [ 2his1met ] motif was successfully created in the single mutant of r118h mb and r118 m mb , respectively . uv / vis kinetic spectroscopy and epr studies further revealed that both the heme site and the designed copper site exhibited nitrite reductase activity . this study presents a new example for rational protein design with multiple active sites in a single protein scaffold , which also lays the groundwork for further investigation of the structure and function relationship of heme / nonheme proteins .

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we investigated a tbe outbreak , comprising 6 cases , in a mountain region in western austria in july 2008 . the index case occurred in a 43-year - old shepherd who had stayed for 24 days at his alpine pasture ( 1,564 m above sea level ) before he was hospitalized for nonbacterial urethritis and nonspecific influenza - like symptoms ( including pain in the lower abdomen and legs ) , followed by clinical signs of meningitis . tbev infection was confirmed serologically by elisa demonstration of specific immunoglobulin ( ig ) m and igg in serum and cerebrospinal fluid . the patient did not remember a tick bite but had eaten self - made cheese prepared from a mixture of nonpasteurized goat milk and cow milk 811 days before illness onset ; further investigation found 6 additional persons who had eaten the same cheese ( figure ) . for 5 of them , recent tbev infection was serologically proven ( table ) . for 3 of these persons ( 2 men , 44 and 65 years of age ; and 1 woman , 60 years of age ) , similar to the index patient , a typical biphasic course and symptoms of tbe ( nonspecific flu - like symptoms followed by fever , cephalea , meningism , and ataxia after 410 days ) developed and they were hospitalized . the 2 other persons who had eaten the cheese ( female , 37 and 7 years of age ) were clinically asymptomatic . the noninfected person had vomited shortly after eating the cheese because of a gastric banding . time course and series of events of a tick - borne encephalitis ( tbe ) outbreak from cheese made with goat milk . week 0 , transport of goat to high altitude ; , onset of disease ; o i , hospitalization period ; tbev , tick - borne encephalitis virus ; me , meningoencephalitis . * tbev , tick - borne encephalitis virus ; nt , neutralization test ; csf , cerebrospinal fluid ; ig , immunoglobulin ; me , meningioencephalitis ; pos , positive ; bor , borderline ; na , not applicable ; neg , negative . the cheese was prepared from a mixture of fresh milk from 1 goat and 3 cows and was eaten shortly after production . detection of tbev - specific hemagglutination inhibiting ( hi ) and neutralizing antibodies in the goat s serum proved infection in the goat ; the 3 cows were seronegative for tbev . at the time of this investigation ( 1 month after cheese production ) , tbev was already undetectable by pcr in serum and milk of the goat . cheese from the 3 batches produced after the contaminated batch was tbev negative by pcr . the 4 domestic pigs kept at the alpine pasture and fed with the whey and goat milk , however , were seropositive ( tbev hi- and neutralizing antibodies detected ) , which indicated tbev infection , but no clinical signs were observed . serum samples from 105 goats from pastures in the neighborhood also were investigated for tbev - specific antibodies ; all goats were seronegative . our analyses showed that the 6 humans and the 4 pigs were infected through the milk of 1 goat , which had been transported by car from a tbe nonendemic valley to the alp 12 days before production of the tbev - contaminated cheese . experiments have demonstrated that infected domestic animals ( i.e. , goats , sheep , and cows ) can excrete tbev into milk for 37 days , beginning as early as the second or third day postinfection ( 69 ) . in addition , although cheese was produced once or twice each week , only this 1-kg batch of cheese transmitted tbev . therefore , all the evidence indicates that the goat was infected at the alpine pasture at an altitude of 1,564 m. indeed , some ticks were collected from cows that had stayed at this altitude during the entire summer . analyses of these ticks for tbev by pcr , however , yielded only negative results . our findings provide further evidence for the expansion of tbev - endemic regions to higher altitudes in central europe . for example , longitudinal studies in the czech republic , a country with similar climatic and ecologic conditions to those of austria , showed a shift in ixodes ricinus ticks and tbev , from 700 m in 19811983 to 1,100 m altitude in 20012005 ( 10,11 ) . likewise , zeman and benes demonstrated that the maximum altitude at which tbev is found in the czech republic gradually moved upward during 19702000 , corresponding to the rise in temperature during the same period ( 12 ) . in scandinavia , a northward extension of the geographic range of i. ricinus ticks and tbev since the mid-1980s has also been recognized ( 1,1315 ) . climatic changes most likely are the major driving forces for the geographic changes in the distribution of tbev and its main vector , i. ricinus , in europe . this report also emphasizes the efficiency of oral transmission of tbev to humans and to pigs . six of the 7 persons who ate the cheese and all 4 pigs fed residual milk or whey from the same cheese became infected . given the excellent effectiveness of the tbe vaccine ( 2 ) , vaccination probably could have prevented all 6 human cases .

we report transmission of tick - borne encephalitis virus ( tbev ) in july 2008 through nonpasteurized goat milk to 6 humans and 4 domestic pigs in an alpine pasture 1,500 m above sea level . this outbreak indicates the emergence of ticks and tbev at increasing altitudes in central europe and the efficiency of oral transmission of tbev .

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neurofibroma is a benign peripheral nerve sheath tumor arising from the schwann cells and perineural fibroblasts . oral involvement is noted in 3.4 - 92% of adults and 40% of children with nf1 . a 28-year - old male patient reported [ figure 1 ] with the chief complaint of a painless swelling in the right upper back tooth region since 3 years . history revealed swelling was of insidious in onset , which increased to attain the present size . family history revealed the patient 's father [ figure 3 ] also had multiple swellings all over the body and face . on general examination , multiple swellings all over the trunk region and arms were observed [ figure 2 ] . solitary well - defined oval shaped swelling [ firm in consistency and nontender on palpation figure 4 ] approximately 4 cm 3 cm was present in the right maxillary posterior region extending from distal aspect of maxillary first premolar to mesial aspect of third molar . . however , multiple , discrete , sessile cutaneous masses which had started appearing since childhood were observed . histopathological examination of incisional biopsy of the oral lesion showed spindle cells with elongated wavy nuclei . the lesional area was separated from the overlying epithelium by mature fibrous connective tissue [ figure 5 ] . cutaneous neurofibroma over the trunk patient 's father with cutaneous neurofibroma gingival neurofibroma h and e stained section of the lesion under , 40 neurofibromatosis type 1 is due to alteration of nf1 gene , which is a tumor suppressor gene located in the long arm of chromosome 17 . the clinical criterion for the diagnosis of nf1 encompasses presence of six or more cafau lait spots ( > 5 mm in children or > 15 mm in adults ) , two or more cutaneous or subcutaneous neurofibromas or one plexiform neurofibroma , freckles in the axilla or groin optic glioma , two or more lisch nodules ( pigmented hamartomas of the iris ) , bony lesion with sphenoid wing dysplasia or bowing of the long bones with or without pseudoarthrosis , and/or first degree relative with nf1 . other features that have been described to occur variably in individuals with nf1 include short stature , large head size , failure to gain weight , precocious puberty , vascular disease including childhood hypertension , neural problems secondary to the spinal cord involvement , headaches , cognitive problems , stroke , brain tumors , and rarely tumors such as pheochromocytoma , and juvenile chronic myeloid leukemia . common sites of the oral solitary neurofibromas include tongue ( 26% ) , buccal mucosa ( 8% ) , alveolar ridge ( 2% ) , labial mucosa ( 8% ) , palate ( 8% ) , gingiva ( 2% ) , nasopharynx , paranasal sinuses , larynx , floor of the mouth and salivary gland . this patient reported with gingival localization of neurofibroma , which is extremely rare and unique . gingival neurofibromas can cause periodontal disease , as tissue growth is an obstacle in carrying out routine oral hygiene measures . oral radiographic findings unique to nf include lengthening , narrowing and rarefaction of coronoid and articular process , deepening of sigmoid notch , an enlarged mandibular canal , mandibular foramen and mental foramen . other findings are shortening of the ramus , notching of the inferior border of the mandible . in the case usually , the prognosis for solitary neurofibroma is extremely good , with only rare instances of recurrence . the present case was kept under observation and was recalled every 3 months for a period of 1 year and showed no signs of recurrence . malignant transformation of neurofibromas with nf1 into neurogenic sarcomas bears a very bad prognosis with a 5 years survival rate of just 15% . long - term review of patients and genetic counseling is recommended owing to the likelihood ( 50% ) of vertical transmission . it is imperative for the general physicians and dermatologists to be aware of the oral manifestations of nf1 considering the risk of malignant transformation and the poor prognosis .

neurofibroma is a benign peripheral nerve sheath tumor and is the most frequent tumor of neural origin . its presence is one of the clinical criteria for the diagnosis of neurofibromatosis type 1 ( nf1 ; a common hereditary disease occurring in one out of every 3000 births ) . the diagnosis can sometimes be made at birth , while in others the diagnosis is made later in life after the appearance of additional clinical criteria . majority of the solitary neurofibromas are sporadic , while a few are associated with nf1 syndrome . oral hard and soft tissue are affected by the tumor ; however , the tongue is the most affected site . gingival neurofibroma is an uncommon oral manifestation of nf . here , we report a rare case of gingival neurofibroma in nf1 patient . one of the most feared complications of nf1 is its transformation into neurofibrosarcoma , which bears a very poor prognosis . treatment of neurofibroma is surgical resection .

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chorea may be the manifestation of a wide variety of degenerative , vascular , metabolic , or toxic disorders involving the central nervous system , in which dysfunction of the basal ganglia , particularly of the striatum , is generally assumed to be responsible . we report an index case of generalized chorea secondary to the ingestion of propiconazole toxin ( fungicide ) in a young female . in this case , the patient was a 35-year - old lady who was a known case of primary juvenile myoclonic epilepsy , on treatment with valproate ( 800 mg / day ) for 7 years . she was found in unconscious state at home by the family , who then took her to the emergency department of another facility . in view of prior history of epilepsy , three days later , due to persistent unresponsive neurological condition , she was referred to our tertiary care hospital for further management . at admission , her glasgow coma scale was e2m5v1 , with bilateral small - sized pupils ( 2 mm , reacting ) , heart rate of 64/min , blood pressure 90/60 mmhg on inotropic support with norepinephrine 2 g / kg / min and dopamine 8 g / kg / min . blood biochemistry and metabolic profile were normal with total leukocyte count-12,000/mm , rbs-85 mg / dl , blood and urine culture were sterile . electroencephalogram was done to rule out status epilepticus while the patient was on valproate ( blood level-80 ) and no sedatives . magnetic resonance imaging ( mri ) brain with contrast , and cytological and biochemical analysis of cerebrospinal fluid were normal . on day 3 of her illness when inotropes had been tapered , her heart rate was in the range of 5058/min . bradycardia ( even with inotropic support ) along with small - sized pupils raised the suspicion of intoxication . furthermore , relatives were redirected to look for any evidence of suspicious compound at home . cholinesterase levels were very low ( 134 ) along with an empty bottle of propiconazole toxin ( fungicide ) found at home , confirming the diagnosis of intoxication . however , on the 9 day of her illness , she developed irregular random flowing movements from one part of the body to another , suggesting generalized chorea [ video 1 ] . a detailed family history was not positive for any chorea / choreiform movements suggestive of inherited degenerative disorders . the patient was extensively evaluated for other acquired cause of chorea , but her hematological investigations including peripheral blood film , biochemical , thyroid function , serum valproate levels , and vasculitic workup were negative and repeat mri brain and computed tomography ct abdomen were also normal . she was treated with clonazepam ( 2 mg ) , tetrabenazine ( 75 mg ) , and risperidone ( 2 mg ) with partial improvement in chorea . our case depicts initial diagnostic dilemma , which is frequent problem in intoxication as history is often concealed . hence , insecticide poisonings are relatively a common occurrence with wide spectrum of neurological presentations which may affect the function of the central and peripheral nervous system . clinical manifestations vary greatly , and include movement disorders such as secondary parkinsonism and a wide range of hyperkinetic disorders and even delayed neuropathy . propiconazole is the triazole class of fungicide and is available as an emulsifiable concentrate ready - to - use liquid [ figure 1 ] . it is also known as dmi or demethylation - inhibiting fungicide , due to its binding with and inhibition of 14-alpha - demethylase enzyme . to the best of our knowledge , this is the index case of generalized chorea following intoxication with propiconazole ( fungicide ) . the probable mechanism may be excessive acetylcholine activity in the nigrostriatal system due to inactivation of acetylcholinesterase by propiconazole . within the nigrostriatal network , caudate nucleus and globus pallidus are particularly rich in cholinergic neurons causing less inhibition of pallidothalamic fibers and generalized choreiform movements . chemical structure of propiconazole ( c15h17cl2n3o2 ) the neurological manifestation with propiconazole intoxication is not reported in literature . only few cases of extrapyramidal manifestations following cholinergic intoxication secondary to organophosphate poisoning ( opc ) have been described . in the three cases described by joubert et al . , the extrapyramidal manifestations were limited to choreiform movements . although exact mechanism of action of propiconazole is not clear , but circumstantial evidence , low cholinesterase levels , and response to anticholinergic treatment sufficiently support our diagnosis . with delayed development of generalized chorea as neurological sequelae , propiconazole may be added as another compound in the causal list of toxic chorea widening the spectrum of acquired toxic causes of chorea still further . in a country like ours , where poisonings are frequent exposure to toxic agents

chorea is a rare manifestation of poisoning . we report an index case of a young woman who developed generalized chorea following propiconazole toxin ingestion . as large series on neurological complications of toxic compounds are difficult to be compiled , it is of interest to report our experience . this report adds one more compound to the increasing list of toxic chorea .

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neuroendocrine tumors of the lung include atypical and typical carcinoids , large cell neuroendocrine carcinomas and small cell lung carcinomas . typical carcinoids ( tcs ) and atypical carcinoids ( acs ) of the lung have rapidly increased in the last 30 years with an incidence of 1.57/100.000 in 2003 . tcs are often regarded as benign due to their low proliferation rate ( ki-67 < 2% ) . the treatment of choice is surgery , which can be curative in most cases . although tcs share histologic features with gastroenteropancreatic neuroendocrine tumors ( gep - nets ) , they exhibit a lower tendency to form secondary tumors . tcs express thyroid transcription factor-1 ( ttf-1 ) and cd56 , whereas gep - nets do not . despite their low proliferation rate , tcs may recur and metastasize . currently , there are no specific guidelines for preoperative staging or follow - up of typical lung carcinoids . follow - up of these patients is often individualized and somatostatin receptor ( sstr ) based positron emission tomography ( pet)/computed tomography ( ct ) is rarely performed . bronchoscopy was normal . preceding surgery , a [ f]fluorodeoxyglucose ( fdg)-pet / ct scan was performed as recommended for staging of pulmonary tumors . figure 1(a ) [ f]fdg pet / ct located a tumor with low glucose uptake in the lingula . ( b ) [ ga]sstr - pet / ct detected somatostatin receptor positive lesions in the terminal ileum and peripancreatically . ( a ) [ f]fdg pet / ct located a tumor with low glucose uptake in the lingula . ( b ) [ ga]sstr - pet / ct detected somatostatin receptor positive lesions in the terminal ileum and peripancreatically . pathology demonstrated a 12 mm typical carcinoid ( ki-67 < 5% , see fig . none of the lymph nodes removed were invaded ; the final staging was pt1 pn0 cm0 . after surgery , follow - up was performed every 3 months by ct of the chest . it was noted that tumor marker chromogranin a was increasing in december 2010 and the patient was complaining about recurrent abdominal pain . sstr - pet / ct with [ ga]dota - tyr3-octreotide pet / ct ( [ ga]dotatoc ) was performed and demonstrated a tumor in the terminal ileum associated with an enlarged parapancreatic lymph node ( fig . a radical right hemicolectomy encompassing lymphadenectomy was performed in february 2011 , using gamma probe detection after [ ga]dotatoc was given as tracer . pathology revealed a well - differentiated net from the ileocecal valve ( size 10 mm , fig . the final union for international cancer control ( uicc ) staging was pt2 , pn1 , pm0 , g1 , l0 , v0 , r0 , pn0 . 4c ) , somatostatin receptor 2a and cdx-2 , but negative for ttf1 ( fig . 5c ) indicating an intestinal origin without any relation to the tc removed 4 years earlier . ( d ) ttf-1 : lung . ( a ) net of the ileum ( 1.0 cm ) after ileotomy . this case report describes the occurrence of two non - related well - differentiated nets in a single patient detected within 4 years . the first net demonstrated pathologic features of a pulmonary tc and the second , also a well - differentiated net , originated from the ileocecal valve . the intraoperative exertion of a gamma probe often results in the extension of the planned surgical procedure , especially in an extended lymph node resection . it permits the identification of previously occult metastases and the localization of hidden lymphatic lesions . although little is known about development of second nets in patients without multiple endocrine neoplasia syndromes , follow - up of patients with nets using sstr - pet / ct will help in the detection of tumor recurrence or other non - related nets . in our patient , the second net was only detected by a somatostatin receptor pet / ct 4 years after curative surgery of the tc of the left lung . 5a ) , it can be assumed that this tumor was already present in 2007 , however [ f]fdg / pet usually does not detect gep - nets with a low proliferation rate . in our case , after removal , we performed only local staging using thorax ct and bronchoscopy . if the net diagnosis is discovered after surgery , similar to gep - nets , systemic molecular imaging ( [ ga]sstr - pet / ct or octreotide scintigraphy ) must be performed postoperatively . this rules out occult metastases and provides reference imaging for further comparative follow - up studies . however , because of the limited availability of this molecular imaging technique , it does not allow routine staging after surgery . in our opinion , this imaging procedure should be reserved for when increasing levels of biomarkers or clinical symptoms indicate a recurrence . if the net diagnosis is known or presumed preoperatively , accurate preoperative staging and a postoperative comparative study from the resection results are enabled through this imaging technique . this case report illustrates the clinical utility of sstr - pet / ct for the detection and follow - up of patients with nets of the lung and gastroenteropancreatic system .

abstractwell - differentiated neuroendocrine tumors ( nets ) of the lung occur as typical and atypical carcinoids . little is known about the biology of these tumors in respect of their ability to metastasize or the probability of development of concomitant neuroendocrine tumors . here we report a patient diagnosed with a second neuroendocrine tumor of the ileum 4 years after curative resection of a typical carcinoid of the left lung . the intestinal neuroendocrine tumor was successfully detected by gallium-68 based somatostatin receptor positron emission tomography ( pet)/computed tomography ( ct ) and surgically removed using gamma probe detection based on the same labeling . this case report underlines the utility of somatostatin receptor pet / ct based detection and follow - up of nets .

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a technique of orthotopic rat liver transplantation has been shown in a recent journal of visualized experiments paper . portal vein and infra - hepatic vena cava anastomoses were performed using the quick - linker assisted cuff technique . this technique was chosen among other revisions of the original kamada 's technique , as it allows for easier and quicker anastomoses , results in a better hemodynamic , and can be implemented with a shorter learning curve . the quick - linker technique requires the use of a handle , an approximator and cuffs , all of which can be designed from common laboratory material according to the technique described in the present report . drill a 2 mm hole with a spherical diamond bit , mounted on a high - speed drill . widen the hole with fusiform or conic diamond bits . figures 1 and 2 can be used as stencils . convert the drill into a mini bench grinder and cut off half of one branch under the microscope using the high - speed mini bench grinder . make symmetrical grooves on both sides to allow for the handle to slide in completely . cut a longitudinal slit in the long arm and check that the center of the long arm and a well - positioned handle are on a same axis . make the branch as thin as possible and round off the piece with the low speed rotating brush . take fine - bore polyethylene tubing and round off one edge with an nr 10 scalpel . design a grove 0.5 mm from the edge , and carefully cut out a slope going down to the grove . drill a 2 mm hole with a spherical diamond bit , mounted on a high - speed drill . widen the hole with fusiform or conic diamond bits . figures 1 and 2 can be used as stencils . convert the drill into a mini bench grinder and the approximator is obtained by modifying straight surgical klemmer 's or kocher 's forceps . cut off half of one branch under the microscope using the high - speed mini bench grinder . make symmetrical grooves on both sides to allow for the handle to slide in completely . cut a longitudinal slit in the long arm and check that the center of the long arm and a well - positioned handle are on a same axis . make the branch as thin as possible and round off the piece with the low speed rotating brush . take fine - bore polyethylene tubing and round off one edge with an nr 10 scalpel . design a grove 0.5 mm from the edge , and carefully cut out a slope going down to the grove . this problem was due to the fact that the ring of the handle was too narrow , and it has been solved by setting the narrowest part of the handle ring at 0.5 mm . if printed with a scale 1:1 can be used to guide the handle shaping . click here to view larger figure . if printed with a scale 1:1 can be used to guide the handle shaping . click here to view larger figure . graft 's v.porta should be secured to the central groove , while recipient 's vessel to the lateral one . the present report describes the design and building of the quick - linker system for easier rat liver transplantation . rat liver transplantation is a popular model with 125 to 180 related papers published yearly since the early 1990 's ( www.pubmed.com ) . it allows for a wide range of experiments including the exploration of immunological and graft preservation issues . the use of the " quick - linker " kit allows for easier and quicker anastomoses with guaranteed intima - to - intima contact . a detailed description and discussion of the technical steps of a rat liver transplantation the quick - linker kit can be built at low price from common laboratory material . the main challenge encountered has been related the breakdown of one handle during the final brushing , and that problem has been solved by setting the narrowest part of the handle ring at 0.5 mm ( figures 1 and 2 show appropriate sizes ) . regarding the blade quality , only stainless steel should be considered . although slightly less flexible compared to the average carbon steel blade , stainless steel blades do not develop rust , allowing a lifetime use of the handles . of note , the design of the current handles and cuffs is the result of a process , which has led to the proposed sizes , allowing for the most efficient anastomoses . minimal variations can be tolerated in terms of length , with a usual length of about 4 mm ( figures 3 and 4 ) . regarding the approximator , the selected kocher 's forcep should have handles at least 4 cm from the fulcrum . this allows for a safe closure of the rack outside the animal 's abdomen . overall , the proposed device can allow easier vein anastomoses for the transplantation of liver and other types of grafts in rats .

orthotopic rat liver transplantation is a popular model , which has been shown in a recent jove paper with the use of the " quick - linker " device . this technique allows for easier venous cuff - anatomoses after a reasonable learning curve . the device is composed of two handles , which are carved out from scalpel blades , one approximator , which is obtained by modifying kocher 's forceps , and cuffs designed from fine - bore polyethylene tubing . the whole process can be performed at a low - cost using common laboratory material . the present report provides a step - by - step protocol for the design of the required pieces and includes stencils .

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sarcoidosis is a common systemic disorder of unknown etiology which is characterized by the formation of noncaseating epithelioid cell granulomas . in addition to their occurrence in systemic sarcoidosis , these granulomas have also been observed in various parenchymas and in the lymph nodes associated with other granulomatous diseases . granulomatous reactions occurring within lymph nodes draining carcinomas are a well - known but uncommon occurrence . these histologic changes have been termed sarcoid reactions , and such changes have been described in association with lymphoma and other solid tumors . however , the presence of this response in colorectal cancer has been considered to be quite rare , and only a few reports have mentioned the presence of granulomatous reactions in colorectal cancer . we herein report a rare case of adenocarcinoma of the ascending colon associated with sarcoid reaction in the regional lymph nodes . a 56-year - old japanese man was assessed for anemia . computed tomography of the abdomen performed to investigate the cause of anemia showed a tumor mass in his ascending colon and many enlarged regional lymph nodes ( fig . laboratory data showed no abnormality except for anemia , with 9.0 mg / dl hemoglobin . the past clinical history mentioned hypertension , but neither inflammatory nor immunological disease . a typical ileocecal gross examination of the operative specimen revealed a tumor measuring 70 55 mm at the ileocecal valve , and many enlarged regional lymph nodes were present , suggesting metastasis of the lymph nodes . histopathological examination revealed moderately differentiated adenocarcinoma of the ascending colon which extended to the subserosa . there was no metastasis to the dissected lymph nodes ; however , noncaseous epithelioid granulomas with multinucleated giant cells without necrosis were observed ( fig . we here report a rare case of adenocarcinoma of the ascending colon associated with sarcoid reaction in the regional lymph nodes . an association of sarcoid reaction with malignancy has been reported , and such reactions may occur in lymph nodes draining an area housing a malignant tumor , in the tumor itself , and even in nonregional tissues . sarcoid reactions have been described in association with lymphoma , testicular cancer and other solid tumors . however , this response in colorectal cancer has been considered to be quite rare , and there have been only a few publications that mention the presence of granulomatous reaction in colorectal cancer . the mechanism of tumor - associated sarcoid reaction in the regional nodes has not yet been elucidated . the possible mechanisms are summarized as follows : ( 1 ) a localized defense reaction to tumor cells themselves , ( 2 ) a simple tissue reaction to a tumor embolism in the lymphatic system or capillaries , and ( 3 ) an immunological reaction to substances released from the tumors transported along the lymphatic system [ 2 , 3 , 6 , 13 , 14 ] . sarcoid reaction has also been reported after interferon therapy in patients with malignant melanoma and after interleukin-2 therapy for renal cell carcinoma . thus , sarcoid reactions are most likely caused by antigenic factors derived from the tumor cells and could play an important role in the host 's defenses against metastatic extension . sarcoid reactions may manifest as local t - cell - mediated reactions , and in hodgkin 's disease and gastric cancer there is evidence that patients with sarcoid reactions in the regional lymph nodes have a better prognosis . it has been generally reported that patients with malignant tumors coexisting with sarcoid reactions have a good prognosis because this reaction commonly occurs in lymph nodes without metastasis . in fact , in our case and a few case reports of colon cancer with sarcoid reactions in the lymph nodes , there was no metastatic carcinoma in the dissected lymph nodes despite the large size of the tumor . in contrast , however , according to the few publications that mention lung - cancer - associated sarcoid reaction , such lesions do not influence the prognosis . to elucidate the relationship between this reaction and the prognosis of patients with cancer , especially colon cancer , an investigation based on a larger number of patients fdg - pet is useful for preoperative diagnosis of distant lymph node metastases of colorectal cancers . in present case , 18f - fdg - pet although 18f - fdg - pet is very sensitive for a variety of malignancies , it can lack specificity . in addition to malignant tissue , any active infectious or inflammatory process , including sarcoidosis , can demonstrate fdg avidity [ 6 , 24 , 25 ] . thus , it is difficult to differentiate sarcoid reaction from lymph node metastases preoperatively , and there is no useful examination , except histopathological examination , for distinguishing lymphadenopathy caused by a sarcoid reaction from metastatic lymph nodes . in conclusion , we report a rare case of colon cancer with sarcoid reaction in the regional lymph nodes . the effect of the response on the prognosis in cases with colon cancer has not been fully elucidated due to the small number of such cases , and further analyses from a large number of cases are warranted to evaluate the relationship between sarcoid reaction and colon cancer .

lymph node swelling in the setting of malignancy generally suggests metastasis of the primary tumor . a granulomatous reaction , i.e. sarcoid reaction , occurring within the lymph nodes draining carcinomas is a well - known but uncommon occurrence . the phenomenon is especially rarely seen in colon carcinoma . we herein report a rare case of a 56-year - old japanese male with adenocarcinoma of the ascending colon associated with sarcoid reaction in the regional lymph nodes . a typical ileocecal resection and lymph node dissection were performed . histopathological examination revealed moderately differentiated adenocarcinoma of the ascending colon , and the dissected lymph nodes included epithelioid granulomas with multinucleated giant cells . these findings suggest the existence of a sarcoid reaction associated with colon carcinoma ; there was no metastasis in the dissected lymph nodes . the significance of this rare condition is discussed .

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a 46-year - old gentleman presented with sudden onset of loss of vision following blunt trauma to the right eye . the patient had sustained the injury when he was assaulted with a stone . he had undergone cataract surgery with posterior chamber ( pc ) iol in the right eye three months ago elsewhere . on examination his visual acuity was perception of light , accurate projection of rays in the right eye and 20/30 , n6 in the left eye . anterior segment evaluation revealed iol haptic ( " j " type ) extrusion through the scleral tunnel with hyphema , aniridia and posterior capsular remnant in the right eye [ figs 1,2 ] . his intraocular pressure ( lop ) was undetectably low in the right eye and 16mmhg in the left eye . he was diagnosed to have traumatic rd with vitreous hemorrhage with iol extrusion with total aniridia . he was advised iol haptic explantation , vitreoretinal surgery with encircling band and silicone oil . intraoperatively , after clearing the vitreous hemorrhage , the total rd was evident , with two peripheral retinal tears . the breaks were well supported after the application of silicon encircling band ( mira - 240 with a width of 2.5 mm ) . hence c 3 f 8 ( perfluoropropane ) gas was used as a tamponade . . the inferior and nasal 180 posterior capsule was intact and was left behind for a secondary implant later . at six weeks follow - up his best - corrected visual acuity ( bcva ) was 20/120 + 1 , ni0 with aphakic correction . anterior segment evaluation showed aphakia with aniridia and posterior capsular remnant in the right eye [ fig . 3 ] . indirect ophthalmoscopy showed attached retina with epiretinal membrane ( erm ) and mild macular pucker in the right eye [ fig . follow - up bcva was 20/80 ( hazy ) , n8 in the right eye with correction . fundus examination showed attached retina with erm and internal limiting membrane striae in the right eye . optical coherence tomography ( oct ) showed erm and cystoid macular edema ( cme ) . he underwent secondary aniridic pciol ( io care baroda ; optic 10 mm , central 2.25 mm opaque with surrounding 5.5 mm clear , a constant 118.2 ) with erm removal in the right eye under local anesthesia . although a scleral fixated iol was planned , the iol when placed on the inferior capsular rim was found to be stable . the posterior capsule had fibrosed since the injury and hence provided adequate support without the need for scleral fixation . moreover , since the iol was rigid and measured 12.75 mm in length , it was found to be stable in the scleral sulcus . the incision had to be widened to 10 mm to accommodate the iol . at six weeks follow - up his bcva was 20/30 and n6 , with -2.00 diopter cylinder x 170 and lop was 15 mmhg . indirect ophthalmoscopy revealed normal disc , macula and attached retina with good buckle effect [ fig . optical coherence tomography revealed resolution of cme . at six months follow - up the above findings were maintained . these patients often describe discomfort or difficulty in brightly lit areas , such as on sunny days . a history of blunt trauma besides damage to the iris ; tends to be associated with trauma to the angle or zonules . the most common of these are traumatic cataract , retinal detachment and vitreous hemorrhage . both penetrating and blunt injuries can cause traumatic total iridectomy.1 in our case there was significant damage to the iris with a crescent of posterior capsule intact . iridoplasty , colored contact lenses and corneal tattooing have been developed to overcome the visual function impairments that arise from damage to the iris.2,3 however , when significant amounts of iris tissue are damaged or missing , iris repair may be impossible . in these eyes , several ophthalmologists have used this artificial iris implants called aniridic iol in patients with traumatic and congenital aniridia.4 additional procedures along with iol implantation may be required , including cataract surgery , transscleral iol fixation , keratoplasty and vitreoretinal procedures . a combined aniridic iol implantation and vitreoretinal procedure is possible without significant intraoperative complications.5 a black diaphragm iol design allows simultaneous treatment of aniridia and aphakia6 as was the situation in our case wherein the previously implanted iol had extruded through the scleral tunnel and was removed in the first sitting along with retinal detachment surgery . at the second sitting the aniridic iol the patient did not suffer from any of the complications associated with such similar procedures such as , persistent intraocular inflammation , glaucoma , endophthalmitis and residual photophobia . the patient had good visual recovery , with his vision being 20/30 on his last follow - up six months after the surgery . we present a rare case of traumatic aniridia with vitreous hemorrhage and retinal detachment , in which a good visual outcome was achieved after a combined surgery . after a detailed medline search , there were less than five such cases reported in the literature . both the cost factor and surgical time could be reduced with a combined approach giving an excellent cosmetic , visual and surgical outcome .

a 45-year - old man presented with post - traumatic aniridia . we describe the combined surgery done to treat both aniridia and epiretinal membrane simultaneously . a combined aniridia intraocular lens and vitreoretinal surgery was done . the case report highlights the advantage of combined surgery in terms of cost factor and surgical time .

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eed is a localized , low - grade form of leukocytoclastic vasculitis of unknown pathogenesis characterized by persistent , symmetrical , red - purple papules , nodules , and plaques affecting the extensor surfaces of the extremities , the ears , trunk and buttocks . dermatitis herpetiformis is an autoimmune blistering disease characterized by granular deposits of immunoglobulin a ( iga ) in dermal papillae . the common link between these two disorders is the deposition of ig a antibodies , underlying gluten sensitivity in both , their association with celiac disease and response to treatment with dapsone . a 50-year - old male presented with firm skin - colored and erythematous nodules over the knuckles , elbows , buttocks , knees , and lower legs which gradually increased in size in since 3 years duration [ figure 1 ] . complete blood picture , liver function tests , urine routine , blood sugar were within normal limits . biopsy of the nodules of the knuckles showed focal parakeratosis and mild spongiosis in the epidermis , perivascular neutrophilic infiltrate in the dermis , neutrophils in the vessel wall and leukocytoclasia [ figure 2 ] . immunofluorescence showed linear iga deposits in the basement membrane zone and weak granular perivascular c3 and fibrinogen deposits [ figure 3 ] . four years ago itchy vesicles over the back and arms were detected in the patient . he was administered dapsone which leads to disappearance of lesions with recurrence after stopping treatment . with the clinical presentation , biopsy and immunofluorescence results , a diagnosis of erythema elevatum diutinum on a background of dermatitis herpetiformis was made . skin - colored nodules over the knuckles neutrophilic vasculitis with leucocytoclasia ( h and e , 400 ) linear iga deposits in the basement membrane zone dermal papillary microabscess ( h and e , 400 ) erythema elevatum diutinum ( eed ) is a rare cutaneous condition that initially presents as leukocytoclastic vasculitis ( lccv ) of the skin and later resolves with fibrosis clinically characterized by persistent red - purple to yellow papules , plaques , and nodules . the symmetrical lesions typically affect the acral surfaces of the body , especially the extensor surfaces of the hands , but other areas such as the buttocks may also be involved . antecedent bacterial infections , collagen vascular diseases , myeloproliferative diseases , human immunodeficiency virus infection , cryoglobulinemia , wegener granulomatosis , crohn disease , systemic fungal diseases , iga paraproteinemia , and other associations have been reported . histopathologically , eed initially presents as a leukocytoclastic vasculitis ( lccv ) with polymorphonuclear neutrophils , extravasated red cells , nuclear dust , and fibrin deposits in the walls of the small arterioles . dermatitis herpetiformis ( dh ) is characterized by chronic , intensely pruritic , polymorphic , vesicles usually appearing on elbows , knees , buttocks , and scalp associated with gluten - sensitive enteropathy there are granular iga deposits in the dermal papillae by the direct immunofluorescence in the perilesional skin of patients with dermatitis herpetiformis . the close association of iga with erythema elevatum diutinum and dermatitis herpetiformis is well known . because of the association with iga , the presence of erythema elevatum diutinum in a patient with chronic dermatitis herpetiformis is not surprising . the iga in the skin may be an epiphenomenon or may represent deposition in the skin along with other immune complexes . aftab mn et al . have reported a case of erythema elevatum diutinum arising in the setting of dermatitis herpetiformis . they concluded that iga immune complexes within the basement membrane zone region may trigger a cascade that eventuates into a blister or the formation of the chronic vasculitis of erythema elevatum diutinum .

erythema elevatum diutinum ( eed ) is a rare skin disease that initially presents as leucocytoclastic vasculitis and later resolves with fibrosis . dermatitis herpetiformis is an autoimmune blistering disease characterized by granular deposits of immunoglobulin a ( iga ) in dermal papillae . we report a rare association of these two disorders .

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a 61-year - old woman came to our attention and was hospitalized for the acute onset of fever ( 38c ) , erythroderma , and pustulosis ; the pustules were mainly localized on her shoulders , upper arms , and trunk [ figure 1 ] . in the latter area clinical history revealed that she had been treating a bacterial inguinal intertrigo for 4 days with ciprofloxacin 500 mg tablets twice daily and desloratadine 5 mg tablet once daily . she referred that she had already taken ciprofloxacin in the past for refractory urinary tract infections . laboratory tests showed leukocytosis ( 23,000/ml , nv 390011700 ) , neutrophilia ( 86.4% , nv 39.674.7 ) , increased c - reactive protein ( 188 mg / l , nv < 8) , increased fibrinogen ( 505 mg / l , nv 200400 ) , increased d - dimers ( 4.8 mg / l , nv < 0.5 ) , slightly increased urea ( 41 mg / dl , nv 1538 ) , and decreased glomerular filtration rate ( 66 ml / min , nv > 90 ) . skin biopsy showed a nonfollicular , subcorneal , neutrophilic pustule with eosinophils , histiocytes , mild spongiosis , and moderate papillary dermal edema . erythroderma and pustulosis of our patient at the first day of hospitalization the cutaneous morphology , course , histological findings , and laboratory examinations were consistent with a definite diagnosis of agep according to the validation score of the euroscar study group ; we therefore reported it to italian pharmacovigilance . we immediately stopped the ciprofloxacin and started infusional therapy with methylprednisolone 40 mg once daily and trimeton ( chlorphenamine ) 10 mg twice daily . the rash significantly improved within a few days ; after complete resolution of the lesions , patch tests and lymphocyte proliferation test performed with ciprofloxacin both resulted negative . the most important step of agep diagnosis is to identify the provocative agent : if it is a drug , it must be discontinued immediately , if an infection , immediately treated . commonly , agep is caused by penicillins and cephalosporins , sometimes by fluoroquinolones ( especially norfloxacin and ofloxacin ) . to the best of our knowledge , this is the third reported case of agep caused by ciprofloxacin , supporting two other previous reports . in 2005 , knoell and lynch reported the case of a 63-year - old man with a photoinduced acute exanthematous pustulosis ( an unusual form of agep ) caused by ciprofloxacin and exposure to ultraviolet light . diagnosis was made on the basis of clinical and histological findings . in the same year , hausermann et al . reported another case of ciprofloxacin - induced agep in an 80-year - old woman who also showed a positive patch test to the drug . patch testing with the drugs involved is a useful and noninvasive way to identify the culprit agent of agep but is characterized by low sensitivity , being positive in about 60% of cases . the lymphocyte proliferation test seems promising but likewise has low sensitivity . as in our case , a negative reaction to these tests should not prompt a reconsideration of the diagnosis that remains primarily clinical .

acute generalized exanthematous pustulosis ( agep ) is an uncommon and self - limiting skin rash commonly caused by drugs and is characterized by the acute onset of fever , pustulosis , and neutrophilia from 4 to 10 days after the drug intake . we describe a case of agep in a 61-year - old woman that was hospitalized for the acute onset of fever , erythroderma , and pustulosis . clinical history revealed that she had been treating a bacterial inguinal intertrigo for 4 days with ciprofloxacin 500 mg tablets twice daily and desloratadine 5 mg tablet once daily . to the best of our knowledge , this is the third reported case of agep caused by ciprofloxacin , supporting two other previous reports .

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psychocutaneous diseases can present either as primary psychiatric diseases such as dermatitis artefacta and delusions of parasitosis or as secondary psychiatric conditions such as depression , anxiety or social phobia due to chronic dermatoses like psoriasis , atopic dermatitis , alopecia areata . while in the former group , the diagnosis is usually straight forward , in the latter group such as psoriasis , atopic dermatitis etc the associated psychiatric co - morbidity may be missed or overlooked . unless the dermatologist has a special interest in mental health , in a busy practice , the relevant history is not sought . invisible mental disease in addition to the visible skin disease . in chronic skin diseases , patients feel stigmatized especially when lesions are widespread and may also experience depression . even in clinical remission , some may have anxiety about possible relapse in future . the relationship between mind and skin can be understood on the basis of the neuro - immuno - cutaneous - endocrine network . there is a dedicated european society of dermatology and psychiatry that holds a congress biennially . the association for psychocutaneous medicine of north american too holds regular meetings . in india , this subject has received scantattention . case reports and few studies appear from time to time . whilst dermatologists refer cases to psychiatrists , a dedicated liaison clinic is virtually unknown . we discuss the working pattern of the dermatology - psychiatry - clinical psychology liaison clinic set up at manipal in august 2010 . patients with chronic dermatoses such as psoriasis , eczema as well as those with primary psychiatric conditions were recruited by the dermatologist from the general dermatology out patients and referred to the liaison clinic which functions once weekly from 2:30 to 5:00 pm . the psychologist counseled all patients and if stressors were elicited , coping strategies were taught . both specialists discussed the case with the dermatologist and standard dermatologic treatment with or without psychopharmacologic agents and/or psychological interventions were advised . we examined 175 cases ( 117 females ; 58 males ) aged between 10 and 75 years maximum being in the second and third decade . out of 175 , primary dermatological cases constituted 154 ( 88% ) [ table 1 ] and primary psychiatric 21 ( 12% ) [ table 2 ] . the leading primary dermatosis was psoriasis in 40 ( 23% ) while the leading primary psychiatric disease was neurotic excoriations in 6 ( 3% ) patients . out of 92 ( 53% ) who needed psychologic interventions , only 25 ( 27% ) underwent the same . 12 patients ( 48% ) underwent one session while only 3 ( 12% ) had more than five sessions . forty seven patients ( 30% ) with primary dermatosis had an associated psychiatric diagnosis [ table 4 ] the most common being dysthymia in 22 ( 46% ) . the three leading dermatoses with psychiatric co - morbidity were psoriasis , prurigo / generalized pruritus and chronic dermatitis . a major advantage of a combined clinic is the prompt availability of a psychiatrist , dermatologist and a clinical psychologist at a single visit . the stigma of visiting the psychiatry department although has lessened in recent time , stillexists . our clinic functions in an informal manner without any inhibitions for patients about meeting a mental health professional as there are no boards mentioning the designations of the liaison specialists . the number of patients examined can not exceed four or five as detailed interviews are carried out . a level - one dermatologist is a well informed specialist who can treat psychocutaneous diseases but does not bring about psychological change in the patient while a level two dermatologist is one who liaises with a clinical psychologist or psychiatrist bringing about psychological changes . by liaisoning , patient can be treated in a holistic fashion thereby addressing both the psychological and the physical needs . in our study although stress has been implicated in several dermatoses , psoriasis is the one which is mostly associated with . stress induced derangements of epidermal function may precipitate inflammatory dermatoses . nonpharmacologic interventions are stress reducing adjuncts that can enhance the efficacy of standard dermatogic therapies . some of the therapies useful in dermatologic patients are biofeedback , relaxation training , hypnosis and psycho - education . in our study majority of patients were non - compliant with psychological interventions . probably they did not realize the benefit or were not keen on attending the clinical psychology department . this underscores the need for dermatologists to master selected psychological techniques such as relaxation which can easily be taught to patients in the office . 30% of our patients had psychiatric comorbidity which is in agreement with several studies in psychodermatology . in conclusion , dermatologist should liaise with psychiatrists or clinical psychologists when managing psychosomatic dermatoses . in university teaching hospitals dermatologists should familiarize with selected psychopharmacological drugs and simple nonpharmacologic interventions . screening for common psychiatric conditions such as anxiety and depression

psychodermatology is an emerging specialty in dermatology which deals with the interactions between mind and skin . psychocutaneous diseases can be either primary psychiatric or primary cutaneous , with various degrees of associations between psyche and skin . unless the dermatologist cultivates a special interest in this field , many an invisible mental disorder may be missed leading to sub optimal treatment of the visible skin condition . though dermatology psychiatry liaison clinics are common in europe and other western countries , it is just an emerging concept in india . here we describe the working pattern of psychodermatology liaison clinic established in manipal in august 2010 and describe briefly the type of cases attended to .

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ventriculoperitoneal ( vp ) shunting for hydrocephalus is a common neurosurgical procedure in our daily practice . migration of distal part of vp shunt into the adjacent organs including bowel tract , thoracic cavity , heart , scrotum , umbilicus , abdominal wall , and urinary bladder is reported . a case of repeated shunt migration in different organs this is the first case of bowel perforation with transanal extrusion continued with bladder migration and urethral extrusion of peritoneal shunt . we report our case of a child with these unusual complications ; treatment was done by a team involving neurosurgeons and urologists . a 4-year - old boy was admitted to the hospital because of abdominal discomfort . on further examination the first operation was undertaken when he was 2 months old because of his congenital hydrocephalus . the patient went back to the hospital when he was 1 year old because of severe headache . computed tomography ( ct ) scan confirmed a large right porencephaly . his abdominal x - ray revealed that the extruded shunt was the right peritoneal catheter [ figure 2 ] . the result was showing 200 cells found with protein 100 mg / dl , glucose 13 mg / dl , and the culture showed micrococcus sp . urological procedure was performed endoscopically through the urethra to explore the site of migration and potential of leakage . it was found that the shunt was penetrated through the bladder wall just above the trigonal area [ figure 3 ] . we decided to treat conservatively by inserting an urethral catheter to keep the bladder decompressed for optimal healing process . extruded shunt was exposed through the external urethral orificium abdominal x - ray shows the extruded ventriculoperitoneal shunt cathether through the urethral orificium during endoscopic urological surgery , migration site just above the triogonal area of the urinary bladder was identified ( blue arrow ) thereafter , intraventricular antibiotic was administered according to the culture results . one month later , culture of csf was performed and it showed a sterile result . bowel perforation was present in 0.1%0.7% of cases in which colon was the most involved organ , and the most common site of extrusion is anus ( 68.9% ) , followed by scrotum ( 22% ) , umbilicus ( 6.9% ) , and vagina ( 3.2% ) . a case of urinary bladder migration as well as urethral extrusion of vp shunt is extremely rare . there have been various theories proposed such as bioreactivity , local inflammation , infection , and surgical error . the location of the bladder makes it highly unlikely site of perforation , as the catheter must pass through the peritoneum into the extraperitoneal space and subsequently perforate the bladder . in this present case , the first migration of the catheter was into the anus , and this is considered as a frequent event of migration . the second migration into the bladder is a rare case . symptom was only abdominal discomfort and it became obvious after the expose through the urethral orifice . repeated case of shunt migration is an interesting case regarding the pathophysiology and management of this patient . with the history of prior bowel perforation by shunt catheter , and cultures of specimens indicating an infection fixation of the tip catheter at the specific site of the peritoneum is facilitated and then , continuous erosion and perforation of the peritoneum into the bladder was done . the trigonal area , which comprises less muscle layer , was the site of migration in this case . there are three main procedures of shunt removal : gentle pulling , endoscopic surgery , and major open surgery . as per earlier reports , catheter removal is mostly done by open abdominal surgery , but in author 's opinion , removal of the catheter could be done with a less invasive method . in our case presenting per - urethtraly , the catheter was gently pulled out through the urethral orifice . the surgery was then followed by urological endoscopic exploration through the urethra to view the size and location of the perforation . it is believed that the perforation site seals off due to the presence of a chronic fibrous sheath around the shunt tract and requires no aggressive surgical intervention . we found the pitfall of this case to be the lack of detailed history of the previous operation because the patient underwent the surgery in another hospital . the repeated migrations also give us some thought of another option of shunting , for example , ventriculo - atrial shunt . bladder migration and transurethral extrusion is an extremely rare complication of vp shunt . to our knowledge , this is the ninth case reported . the presence of previous abdominal complication and repeated organ perforation indicates predisposition factors which must be sought and handled before any further treatment .

bladder migration and transurethral extrusion is an extremely rare complication of ventriculoperitoneal ( vp ) shunt . only eight cases have been reported in the english literature since 1995 . we report a case of a 4-year - old boy with cerebral palsy , hydrocephalus , and vp shunted on both sides who presented with a protruded distal vp shunt from his urethral orifice . the patient was reported for having previous shunt extrusion through the anus . the patient was treated on by a multidisciplinary approach , involving a neurosurgeon and urologist . shunt removal with simple procedure was smoothly achieved without morbidities . he was discharged home in satisfactory condition .

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guided cell migration requires the generation of polarized plasma membrane protrusions such as filopodia , lamellipodia , blebs and invadopodia . although these protrusions differ structurally and in their composition , they each contribute to cell movement by pushing the leading edge forward . both axonal growth cones and endothelial tip cells display abundant filopodia protrusions ( fig . 2 ) . their dynamic behavior of extension and retraction is reminiscent of antennae probing their environment and are generally thought to serve as environmental sensors that integrate extracellular signals during directed migration . growth cone morphology , reflected for instance by filopodia number , has been correlated with guidance decisions at choice points and filopodia preferentially contact target cells , sometimes over long distance . in vivo experiments with titrated doses of an inhibitor of f - actin polymerization , cytochalasin b , blocked growth cone filopodia formation in grasshopper ti1 neurons and in xenopus retinal ganglion cell neurons . while pathfinding was disrupted in conditions without filopodia , only minor effects were seen on axonal extension , suggesting that filopodia are dispensable for growth but essential for guidance . similarly , in vitro treatment with cytochalasin b abolished glutamate - induced growth cone turning with only slight effects on neurite extension . however , a little known study on retinal ganglion cells suggests that axon guidance can occur without filopodia . here , the authors demonstrate that growth cones extend few or no filopodia after inhibiting ena / vasp function . while axonal elongation was slowed down , retinal ganglion cell axons devoid of filopodia showed normal trajectories in vivo and growth cone navigation across several choice points was unaffected . axonal growth cones ( a , image courtesy of isabelle brunet ) and endothelial tip cells ( b ) extend long filopodia ( arrowheads ) in the direction of migration . scale bars , 10 m . similar to growth cones , endothelial tip cells at the leading edge of vascular sprouts produce many long filopodia that extend toward the direction of vascular growth during angiogenesis . these filopodia express the vegf - a receptor , vegfr2 , and become misdirected and shorter upon disruption of vegf - a distribution in the mouse retina . as filopodia have been proposed to act as sensors of the extracellular milieu and endothelial cells respond to axon guidance molecules such as slits and roundabouts , netrins and unc5 receptors , semaphorins , plexins and neuropilins , and ephrins and eph receptors , it has been widely assumed that they sense and integrate pro - angiogenic and repulsive cues in tip cells to enable guided migration and stereotypic vessel patterning . however , the role of filopodia in vessel guidance has never been proven nor questioned . recently , work from our laboratory demonstrated that filopodia are not essential for mediating endothelial tip cell guidance . by using low concentrations of latrunculin b ( lat . b ) , which prevents f - actin polymerization , endothelial filopodia formation was abolished in the zebrafish embryo . live microscopy revealed that endothelial tip cells of isvs without filopodia continued to migrate along normal trajectories to form the stereotypic isv pattern and to anastomose with other tip cells . at the low concentrations of lat . b used , tip cells were able to generate lamellipodia that provided the driving force for cell movement although at a decreased velocity . furthermore , the induction of new vascular sprouts toward sources of ectopic vegfa165 ensued in the absence of filopodia . in summary , our study shows that during angiogenesis , endothelial filopodia are dispensable for tip cell guidance . this finding complements that of dwivedy et al . , who showed that filopodia are also not essential for axonal growth cone navigation and challenges the long - standing notion that filopodia are required for guided migration . in fact , filopodia or filopodia - like structures have been ascribed many other functions . these include facilitating cell - cell matching and epithelial sheet adherence during dorsal closure in drosophila , transmitting signals such as delta - notch and sonic hedgehog signaling between non - neighboring cells , inducing cell shape changes required for preimplantation embryonic development by providing tension and positioning nuclei in nurse cells during oogenesis in drosophila . in endothelial cells , we propose that filopodia serve as templates from which lamellipodia emerge and that both protrusive structures coordinate to allow efficient migration and expansion of new vascular sprouts . in addition , tip cell filopodia facilitate the process of anastomosis , a process whereby tip cells meet , fuse and establish new junctions to form a connected vascular network . thus , the mechanism(s ) by which blood vessels are guided by extracellular cues is still unresolved .

filopodia are highly dynamic , rod - like protrusions that are found in abundance at the leading edge of migrating cells such as endothelial tip cells and at axonal growth cones of developing neurons . one proposed function of filopodia is that of an environmental probe , which serves to sense guidance cues during neuronal pathfinding and blood vessel patterning . however , recent studies show that tissue guidance occurs unhindered in the absence of filopodia , suggesting a dispensability of filopodia in this process . here , we discuss evidence that support as well as dispute the role of filopodia in guiding the formation of stereotypic neuronal and blood vessel patterns .

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a 44-year - old man , who had a medical history of panic disorder , visited another hospital due to dyspnea on mild exertion . a coronary angiography showed a single coronary artery originating from the right coronary ostium . a single coronary artery bifurcated into the right coronary artery and left main coronary artery . the left main coronary artery coursed between the main pulmonary artery and aorta before bifurcating into the left descending artery and circumflex artery . we thought that panic symptoms or dyspnea on exertion might be a sign of myocardial ischemia due to compression of the left main coronary artery by the pulmonary artery and aorta . we decided that surgical treatment was the best option due to the high risk of sudden death associated with a coronary anomaly . under general anesthesia we dissected the left main coronary artery between the aorta and the main pulmonary artery on the beating heart . the proximal left main coronary artery was bifurcated from a single coronary artery that originated from the right coronary sinus . under cardiopulmonary bypass , only one coronary ostium was observed in the right coronary sinus , and a single coronary artery originated from the ostium . a 5-mm arteriotomy was made to the left main coronary artery at the site in which the left coronary ostium should have been located . neo - ostium formation was performed with a 5-mm puncher in the left coronary sinus . anastomosis between the neo - ostium and the left main coronary arteriotomy site was performed using a 7 - 0 prolene continuous running suture ( fig . the aortic cross clamping time was 88 minutes , and total cardiopulmonary bypass time was 117 minutes . follow - up computed tomographic angiography before discharge showed good patency of the neo - ostium in the left coronary sinus without stenosis at the anastomosis site ( fig . the patient remained asymptomatic without any complications or events for 15 months after the surgery . angelini reviewed 1,950 coronary angiographies and reported that the incidence of right coronary artery originating from the left coronary sinus was 0.92% and vice versa was 0.15% , with a total incidence of 1.07% . patients are usually asymptomatic . however , it may cause angina , syncope , and even life - threatening complications such as myocardial infarction or ventricular fibrillation . thus , we must consider surgical treatment or intervention if signs of myocardial ischemia are present . several surgical techniques can be utilized to treat coronary anomalies , such as coronary reimplantation to the original sinus , coronary artery bypass graft ( cabg ) , pulmonary artery translocation , unroofing , and neo - ostium formation . in this case , the left main coronary artery was bifurcated from a single coronary artery originating in the right coronary sinus . furthermore , the left main coronary artery passed between the pulmonary artery and aorta to reach the left heart . cabg , coronary reimplantation , unroofing or neo - ostium formation could therefore have been considered as viable surgical options . coronary reimplantation is one of the most physiologically beneficial repairs , but is technically difficult , and stenosis may occur at the site of anastomosis . cabg is technically feasible , but the arterial conduit has a competitive flow problem if no stenotic lesions are present on the natural coronary artery . also , a vein conduit may be problematic if the patient is young because of long - term patency . however , extended unroofing may cause valve insufficiency if the anomalous coronary artery is located under the valve commissure . unroofing was not proper for our case because a separated left main coronary artery originated from a single coronary artery , not the right coronary sinus . neo - ostium formation in the left coronary sinus without unroofing was considered to be a proper surgical treatment in this case . successful surgical treatment of anomalous of coronary anomaly depends on expertise in anatomic and hemodynamic pathophysiology , in addition to the selection of the appropriate surgical treatment option . we report that this case was successfully treated with neo - ostium formation in anomalous origin of the left coronary artery from the right coronary system .

anomalous origin of a coronary aortic artery is a rare cardiac anomaly . although it can cause angina , syncope , and palpitations , most patients are asymptomatic . this anomaly requires surgical treatment or intervention because it is associated with sudden death . several surgical techniques , such as coronary reimplantation , coronary artery bypass grafting ( cabg ) , unroofing , and neo - ostium formation , have been proposed as treatments . we report a case surgically treated with neo - ostium formation in anomalous origin of the left coronary artery from the right coronary sinus .

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incidental vessel injury caused by some of these variations may require more extensive lung resection than would be necessary without repair during pulmonary resection . we herein describe a patient with a common trunk of the left pulmonary vein that was incidentally transected with a mechanical stapler during a left upper lobectomy . we also describe the reconstruction procedures that were successfully used for the concomitantly transected inferior pulmonary vein . a 62-year - old man complained of cough and bloody sputum and consulted our hospital . chest computed tomography ( ct ) showed a nodule with a diameter of 15 mm in the left upper lobe . positron emission tomography and brain magnetic resonance imaging revealed a clinical stage of t1n0m0 as categorized by the 7th edition of the union for international cancer control ( uicc ) classification . the common trunk of the left pulmonary vein was misidentified as a superior pulmonary vein until incidental transection with an endostapler during port access surgery . the left upper bronchus and pulmonary arteries to the left upper lobe were transected with endostaplers , and the common trunk of the pulmonary vein was left intact . the left main pulmonary artery was then clamped under intravenous heparin injection to achieve an activated coagulation time of 200 s. annuloplasty of the inferior pulmonary vein was completed during intermittent declamping of the left pulmonary artery . the orifice of the inferior pulmonary vein was augmented by a cuff technique using an orifice of the superior pulmonary vein , as shown in fig . 1 . the staples on the stump of the left common pulmonary vein on the atrial side were removed to adjust the augmented orifice of the left inferior pulmonary vein under partial clamping of the left atrium following pericardiectomy . end - to - end anastomosis was completed using running sutures with a 4 - 0 polypropylene thread . the postoperative course was uneventful , and the patient was discharged on postoperative day 14 . a pathologic study showed stage t1n2m0 small - cell carcinoma as categorized by the 7th edition of the uicc classification . postoperative enhanced ct demonstrated successful reconstruction of the left common trunk ( fig . 2 ) . 1.orifice of an inferior pulmonary vein was augmented with a cuff technique using the orifice of a superior pulmonary vein . the augmented orifice was anastomosed to the common pulmonary vein on the left atrial side after removal of staples as long as necessary under a partial clamp of the left atrium following pericardiotomy . fig . 2.postoperative enhanced ct showing ( frontal view ) successful reconstruction of an inferior pulmonary vein ( arrow ) . orifice of an inferior pulmonary vein was augmented with a cuff technique using the orifice of a superior pulmonary vein . the augmented orifice was anastomosed to the common pulmonary vein on the left atrial side after removal of staples as long as necessary under a partial clamp of the left atrium following pericardiotomy . postoperative enhanced ct showing ( frontal view ) successful reconstruction of an inferior pulmonary vein ( arrow ) . the branching pattern of the pulmonary vessels is variable . pulmonary vein variations such as upper lobe venous drainage posterior to the intermediate bronchus and a common trunk of the left pulmonary vein may cause lethal complications during and after anatomical pulmonary resection . based on ct findings , a common trunk of the left pulmonary vein reportedly occurred with a frequency of 14% among 201 cases . although three - dimensional ct and multidetector ct have been developed to detect pulmonary vessel variations preoperatively , incidental transection of the common trunk may be unavoidable when the pulmonary vein is anteriorly transected with no identification of the inferior vein during left upper lobectomy . furthermore , the use of video - assisted surgery and endoscopic devices has become more widespread , and skin incisions and exposure of anatomical structures have become more limited . a previous paper reported that the orifice of the inferior pulmonary vein was augmented with the use of a pericardial patch followed by anastomosis when the common trunk was incidentally transected . in this report , annuloplasty of the inferior pulmonary vein with a cuff technique using an orifice of the superior pulmonary vein allowed for much easier performance of end - to - end anastomosis , leading to successful reconstruction without a patch or prosthesis . this augmented technique may also be applicable to patients with lung cancer in the right upper lobe when the tumor is invading the right common superior trunk branching pulmonary veins to the upper and middle lobes .

a common trunk of the left pulmonary vein is an anatomical variation in the pulmonary vessels and may be incidentally transected during left upper lobectomy . difficulty in reconstruction of the left inferior vein often requires completion pneumonectomy . we herein describe a patient with lung cancer in the left upper lobe of the lung . his common trunk of the left pulmonary vein was incidentally transected with a mechanical stapler during a thoracoscopic left upper lobectomy . the concomitantly transected inferior pulmonary vein was augmented with a cuff technique using an orifice of the superior vein followed by end - to - end anastomosis . the postoperative course was uneventful . this technique should also be considered in patients with lung cancer when a right upper lobe tumor is invading the right superior trunk branching pulmonary veins to the upper and middle lobes .

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the traditional approach to low back pain ( lbp ) has failed as an effective treatment for lbp patients1 . accordingly , some researchers have recently suggested the necessity of a patient - centered approach to lbp1 . the decreased lumbar spine lordosis induces changes in spinal discs , creating abnormal pressures when absorbing shock between vertebrae , and creating stresses in spinal muscles , tendons and ligaments2 , 3 . flat - back syndrome is characterized by forward inclination of the trunk , inability to stand upright , and lbp pain4 . therefore , the exercises for flat back syndrome include trunk backward extension and pelvic anterior tilt exercises3 , 5 . clinicians recommend various anterior pelvic tilt exercises for lbp with flat back in the lying , sitting , quadriped or standing positions3 , 5 . however , the anterior pelvic tilt motion in these positions does n't apply powerful resistance for anterior pelvic tilt muscle strengthening . the purpose of this paper was to report showed the effect of individual strengthening exercises for anterior pelvic tilt muscles on back pain , pelvic tilt angle , and lumbar rom of a lbp patient with flat back . a 37 year - old male , who complained of lbp pain in l3 - 5 levels with flat back , was participated . ethical approval was obtained from yonsei university faculty of health science human ethics committee , and the subject provided written informed consent to participation prior to the commencement of the study . he complained of continuous lbp for 10 months , and an examination revealed that his pelvis was tilted posteriorly . he had not undergone any specific treatment for his condition , which included mechanical lbp without radiating pain , and in forward flexion in the standing position with his knees fully extended , he experienced pain and stiffness in his lower back . the visual analogue scale ( vas ) score of this back pain was 6 . pelvic inclination was measured with a palpation meter ( palm ; performance attainment associates , st . the intra - test and inter - test reliabilities of the palm are greater than 0.86 . the subject removed his shoes and spread his feet during the measurement , stood upright with the anterior aspect of the thighs against a stabilizing table . the sagittal plane rotation was measured with the caliper tips of the palm in contact with the ipsilateral anterior superior iliac spine ( asis ) and posterior superior iliac spine ( psis ) . at the initial assessment , the anterior pelvic tilt angles were 2 and 2 on the right and left sides ( normal range , 11 4 ) , respectively . the dual inclinometer ( acumar , lafayette instrument co. , lafayette , usa ) was used to measure the trunk flexion and extension angles . the intra - test and inter - test reliabilities of the dual inclinometer are greater than 0.8 . initially , the lumbar flexion angle was 55 and the extension angle was 34. the subject performed individual strengthening exercises for the anterior pelvic tilt muscles ( erector spinae , iliopsoas , rectus femoris)5 . the strengthening exercise for erector spinae was as follows : stand with the feet shoulder width apart with both hands holding 5 kg weights ; then flex the trunk slowly ( 5 seconds ) until parallel with the floor while keeping the natural arch of the back with the shoulder blades back ; then slowly return ( 5 seconds ) to the starting postition . the strengthening exercise for the iliopsoas was an above 90 hip flexion ( so - called psoas isolation ) exercise for both legs with 10 kg weights . the initial position was sitting with the hips and knees flexed at 90 on a table . reciprocal flexion to above 120 hip flexion on both sides was performed with knee flexion of 90. the strengthening exercise for the rectus femoris was an 80 knee extension exercise for both legs with 10 kg weights on a nk table . the subject performed the three individual strengthening exercises for two weeks in three sets of 30 repetitions per day . after the exercise intervention , the anterior pelvic tilt angle increased , the angles were 7 and 8 on the right and left sides , compared to the initial angles of 2 and 2 on the right and left sides . the lumbar roms were increased : the flexion angle was 62 and extension angle was 45 , compared to the initial flexion angle of 55 and extension angle of 34. when in backward trunk extension , the vas score of back pain decreased to a score of 3 , compared to the initial score of 6 . pelvic anterior tilt motion is produced by couple - force of the erector spinae , iliopsoas and rectus femoris muscles5 . during anterior pelvic tilt motion , clinicians ca n't directly apply a powerful resistance to patients for strengthening of pelvic anterior tilt muscles . so , in this study , we tried prescribing individual resistance exercises for pelvic anterior tilt for a lbp patient with flat back . after the intervention , pelvic tilt angles of the right and left sides had recovered to normal ranges . the patient 's lumbar roms had increased , and the vas score of low back pain had decreased . we think that these individual strengthening exercises for the strengthening of pelvic anterior tilt muscles are an effective approach for the treatment of lbp with flat back . therefore , we suggest that individual resistance exercises are necessary for effective and fast strengthening of pelvic anterior tilt muscles in lbp with flat back .

[ purpose ] the purpose of this paper is to report the effect of individual strengthening exercises for the anterior pelvic tilt muscles on back pain , pelvic tilt angle , and lumbar rom of a low back pain ( lbp ) patient with flat back . [ subject ] a 37 year - old male , who complained of lbp pain at l3 - 5 levels with flat back , participated . [ methods ] he performed the individual strengthening exercises for anterior pelvic tilt muscles ( erector spinae , iliopsoas , rectus femoris ) . [ results ] pelvic tilt angles of the right and left sides were recovered to normal ranges . his lumbar roms increased , and low back pain decreased . [ conclusion ] we suggest that individual resistance exercises are a necessary approach for effective and fast strengthening of pelvic anterior tilt muscles in lbp with flat back .

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table 1 summarizes vaccination schedule base on wsava vaccination guidelines in 2010 and aaha vaccination guideline in 2011 . table 1 summarizes vaccination schedule base on wsava vaccination guidelines in 2010 and aaha vaccination guideline in 2011 .

this guideline contains the recommended vaccination schedules of dogs and cats from world small animal veterinary association ( wsava ) and american animal hospital association ( aaha ) . in 2010 , wsava published guidelines for the vaccination of dogs and cats . and , in 2011 , aaha also published guidelines for vaccination of dogs . in korea , there is no published guideline for vaccination of dogs and cats yet . therefore , the plane of vaccination also reports the present situation of vaccination schedule of dogs and cats in korean animal hospitals .

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massive hemoptysis is a life - threatening medical emergency with mortality rates ranging as high as 75% . transcatheter embolization of bronchial arteries has been regarded as an effective and safe method for the management of massive hemoptysis . chronic pulmonary thromboembolism ( pte ) is one of these causes , though its exact incidence remains unknown . compensatory hypertrophy of bronchial arteries is known to occur in chronic pte and pulmonary hypertension . however , the exact mechanism of hemoptysis in these patients is unclear . bleeding due to the rupture of smaller vessels or bleeding from hypertrophied bronchial arteries though bronchial artery embolization has been proposed to be effective in the management of hemoptysis , the ideal treatment for hemoptysis in patients with chronic pte remains uncertain . we report one case of hemoptysis in chronic pte with pulmonary arterial hypertension ( pah ) treated successfully with bronchial artery embolization . a 30-year - old male patient presented to the emergency department of our institute with recurrent bouts of hemoptysis for 1 week , along with shortness of breath . , he was found to have tachycardia ( pulse rate : 100 bpm ) and tachypnea ( respiratory rate : 30 breaths / min ) with decreased oxygen saturation ( 85% in room air ) . the patient underwent computed tomography ( ct ) and bronchial angiography that showed two bronchial arteries on the right side , which were hypertrophied and tortuous ( measuring ~2.6 mm and 2.4 mm , respectively , in maximum caliber ) [ figure 1a ] . in addition , there was a thrombus in the right pulmonary artery , extending from its origin till the subsegmental branches [ figure 1b ] . the right pulmonary artery was reduced in caliber with the dilated main and left pulmonary arteries . two - dimensional echocardiogram ( 2d echo ) was done for the patient that showed severe pah with dilated right atrium and ventricle . on bronchoscopy , active bleeding with clots was seen in the segmental bronchus of the right lower lobe . ( a , b ) coronal maximum intensity projection ( mip ) images of ct bronchial angiography showing hypertrophied right bronchial arteries ( arrows in a ) . one of the bronchial arteries was arising from the intercostobronchial trunk from the descending aorta ( not shown here ) . origin of the second right bronchial artery was , however , not clear on ct angiography . a thrombus was seen in the right pulmonary artery ( arrow in b ) extending till the subsegmental branches the patient was taken up for bronchial angiography . the second bronchial artery was being reconstituted by the internal mammary artery and was hypertrophied [ figure 3 ] . both the bronchial arteries were embolized with polyvinyl alcohol ( pva ) ( 500 - 700 m ) and gelfoam slurry . no other significant systemic collateral was identified on diagnostic runs of the bilateral subclavian arteries . digital subtraction angiogram of the right intercostobronchial trunk ( anteroposterior projection ) showing hypertrophied and tortuous bronchial artery . postembolization angiogram showed no opacification of the distal bronchial artery ( image on the right side ) digital subtraction angiogram of the right internal mammary artery showed hypertrophied second right bronchial artery arising from the internal mammary artery . chronic pte is associated with compensatory hypertrophy of the bronchial arteries and bronchopulmonary collaterals . increased incidence of bronchial artery hypertrophy on ct angiography has been reported in chronic pte and pah . though hemoptysis can occur due to hypertrophied bronchial arteries secondary to any cause , its exact incidence in chronic pte is unknown . one systemic review of the literature reported chronic pte as a cause of moderate - to - massive hemoptysis in 0.1% of cases . we report one case in which bronchial artery embolization was successful in managing hemoptysis in a patient with chronic pte with pah . one patient was successfully treated while the other patient continued to have active hemoptysis due to collaterals from the subclavian artery . reembolization was carried out for this patient but the patient died due to right ventricular failure . it was suggested that due to the requirement of anticoagulation for pte , even mild hemoptysis in these patients should be offered immediate intervention . however , another study reported the failure of bronchial artery embolization to prevent hemoptysis in a patient with chronic thromboembolic pah . in chronic pte , there is a propensity for the formation of thromboemboli . at the same time even mild hemoptysis in these patients should be given prompt treatment due to the underlying risk of progression to massive hemoptysis due to the ongoing anticoagulation therapy . however , very limited literature is available on the management of hemoptysis in chronic pte . no study has been carried out to evaluate the long - term effect of bronchial artery embolization in preventing hemoptysis . also , the precise mechanism of hemoptysis in chronic pte is still not clear . thus , further studies are required to establish the role of bronchial artery embolization in chronic pte .

bronchial artery embolization is the treatment of choice for the management of life - threatening massive hemoptysis . chronic pulmonary thromboembolism ( pte ) is one of the rare causes of hemoptysis . management of hemoptysis in chronic pte is a point of debate . in this article , we have reported one case of hemoptysis in chronic pte managed successfully with bronchial artery embolization .

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patients with obsessive compulsive disorder ( ocd ) have been traditionally described as having a good insight into their symptoms ; they perceive their obsessive - compulsive ( oc ) symptoms as excessive , unreasonable , and distressing . the dsm iv field trial demonstrated that about a quarter of the patients were uncertain about whether their symptoms were unreasonable or excessive , indicating that a broad range of insight exists among patients with ocd . it is now well - recognized that patients with ocd may present with varying degrees of insight , including poor and complete lack of insight into their oc symptoms.[24 ] pathological beliefs appear to be placed along an symptom component properties , they determine obsessions at one end , where beliefs are recognized as irrational . overvalued ideas lie somewhere in the middle , and delusions where the beliefs are considered rational , lie at the other pole . it can be a phenomenological challenge when the thin line of separation between these becomes difficult to discern . ms . s , a 35-year - old , married lady presented with a one - year history of marked social withdrawal , muttering to herself , and suspiciousness . on clarification with her husband regarding her suspiciousness it was found that she kept enquiring from him whether their acquaintances had visited her or not , subsequently she would report about her belief that she felt her acquaintances were not visiting her often , and hence , they could possibly be cheating her , but would not elaborate further . she firmly held on to these beliefs in spite of her husband telling her otherwise . for the last two weeks there had been a worsening of illness , characterized by crying spells , along with two suicidal attempts of high intentionality and lethality . after hospitalization , she was found to be tearful and withdrawn , reported of being fearful and expressed death wishes . an initial impression of psychosis , with a phenomenological inference of delusion of persecution , was made as per the longitudinal course of the illness from the available information , and she was started on tablet risperidone 2 mg . she continued to express fearfulness and did not show much improvement with risperidone . during the course of hospitalization , she was noticed to be repeatedly asking others to forgive her for a mistake she had committed . on further clarification , she elaborated that she had been getting repeated thoughts that she had done something wrong , which could be the reason for her feeling that her acquaintances were not visiting her often . suspicious behavior. she would get these repetitive , anxiety provoking thoughts so often that she started wondering whether she had actually done something wrong . the level of conviction regarding this thought was quite high and she did not feel that this thought was in anyway irrational . hence , she had started feeling , she would constantly ask reassurance from others , would check with her husband as to why a particular acquaintance had not visited her , and would keep repeatedly muttering to herself about this issue . the thoughts were very repetitive , stereotyped , and distressing , while they remained uncontrollable . as the frequency of these thoughts increased , she started feeling sad throughout the day , along with ideas of hopelessness , guilt , and suicidal ideas . subsequently , her diagnosis was revised to obsessive compulsive disorder ( ocd ) , with obsessions of intrusive thoughts / images and compulsion of reassurance seeking as denoted in the yale brown obsessive compulsive scale ( ybocs ) symptom checklist . the ybocs obsession score was 16 and compulsion score was 10 ( ybocs total score of 26 ) . she was started on fluoxetine 20 mg / day , which was increased to 40 mg per day in a week . after two months follow - up , she had significant improvement in her symptoms with the ybocs total score decreasing to 10 . this case demonstrates the importance of eliciting psychopathology in greater detail for specific diagnosis and treatment decisions , especially in the absence of a clear history . the presentation of the case with suspiciousness as the major symptom raised the possibility of psychosis . as there was no morbid illogical reasoning for the belief / thought , delusion was ruled out . additionally , the repetitive nature of the thought , which was stereotyped , causing severe distress , pointed toward a possibility of obsessions . this was supplemented by the compulsive nature of reassurance seeking , which provided some temporary relief to the anxiety caused by the thought . however , the difficulty here was the lack of insight of the patient into this thought phenomenon . even though traditionally viewed as a condition with , egodystonic thoughts recognized as illogical by patients , ocd could present with lack of insight . furthermore , depressive ruminations were usually associated with negative emotions regarding some past event , while in this case the event appeared like an intrusive meaningless thought when it originated . insight in ocd had therapeutic implications such as poorer response to medications and prognostic implications , wherein , schizophrenic spectrum symptoms could lead to worse prognosis . the continuity model between obsessions , overvalued ideas , and delusions seems to be more satisfactory , although it calls for a careful analysis of the phenomenon in clinical settings , for prudent treatment choices .

obsessive compulsive disorder ( ocd ) is commonly regarded as a disorder with good insight . however , it has now been recognized that insight varies in these patients . pathological beliefs seem to lie on a continuum of insight , with full insight at one end and delusion at the other . this can indeed pose a considerable challenge , especially in a scenario where the phenomenon is difficult to discern . we report a case of ocd , which was initially diagnosed as psychosis .

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fear of hypoglycaemia and gain in body weight are barriers for initiation of insulin therapy . modern insulin analogues are a convenient new approach or tool to glycaemic control , associated with low number of hypoglycaemia and favourable weight change . a1chieve , a multinational , 24-week , non - interventional study , assessed the safety and effectiveness of insulin analogues in people with t2 dm ( n = 66,726 ) in routine clinical care . this short communication presents the results for patients enrolled in biphasic insulin aspart sub group from libya . please refer to editorial titled : the a1chieve study : mapping the ibn battuta trail . the study was started with an aim to collect data on all the insulin analogue viz insulin detemir , biphasic insulin aspart and insulin aspart . however , due to ongoing revolution , the complete data could not be collected . here the majority of patients ( 189 ) were started on or were switched to biphasic insulin aspart . other groups were insulin detemir ( n = 58 ) , basal + insulin aspart ( n = 44 ) and other insulin combinations ( n = 25 ) . being the biggest treatment group , this communication describes the results for patients treated with insulin therapy before and then switched to biphasic insulin aspart . overall demographic data 179 patients started on biphasic insulin aspart ogld , and all the patients were on insulin therapy prior to the study . after 24 weeks of switching to biphasic insulin aspart , hypoglycaemic events reduced from 7.2 events / patient - year to 3.7 events / patient - year [ tables 2 and 3 ] . all parameters of glycaemic control improved from baseline to study end [ table 4 ] . overall efficacy data 179 patients started on biphasic insulin aspart ogld , and all the patients were on insulin therapy prior to the study . after 24 weeks of switching to biphasic insulin aspart , hypoglycaemic events reduced from 7.2 events / patient - year to 3.7 events / patient - year [ tables 2 and 3 ] . all parameters of glycaemic control improved from baseline to study end [ table 4 ] . our study reports improved glycaemic control following 24 weeks of treatment with biphasic insulin aspart with or without ogld . hypoglycemic events decreased from baseline and sadrs did not occur in any of the study patients . though the findings are limited by number of patients , still the trend indicates that biphasic insulin aspart can be considered effective and possess a safe profile for treating type 2 diabetes in libya .

background : the a1chieve , a multicentric ( 28 countries ) , 24-week , non - interventional study evaluated the safety and effectiveness of insulin detemir , biphasic insulin aspart and insulin aspart in people with t2 dm ( n = 66,726 ) in routine clinical care across four continents.materials and methods : data was collected at baseline , at 12 weeks and at 24 weeks . this short communication presents the results for patients enrolled in biphasic insulin aspart sub group from libya.results:a total of 179 patients were enrolled in the biphasic insulin aspart subgroup . all the patients were prior insulin users . at baseline glycaemic control was poor ( mean hba1c : 9.3% ) . after 24 weeks of treatment there was an improvement in hba1c ( 0.9% ) . hypoglycaemic events reduced from 7.2 events / patient - year to 3.7 events / patient - year in 24 weeks . sadrs did not occur in any of the study patients.conclusion:starting or switching to biphasic insulin aspart was associated with improvement in glycaemic control with a low rate of hypoglycaemia .

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the 25-gauge curved vitrectomy probe was a prototype manufactured by bausch and lomb ( rochester , ny ) . the length of the probe is 25 mm with a uniform 25-g diameter ( 0.5 mm ) . construction of the illuminated vitrectomy probe is similar to that described previously with a 20-g vitrectomy probe.5 a seamless strong polyester ( polyethylene terephthalate ) heat shrunk tubing ( advanced polymers , inc . salem , nh ) is used to secure a fiberoptic endoilluminator with a curved 25-g vitrector ( [ fig . 1a , b , and 2a ] : vitrector and em).6 the tubing has an internal diameter of 0.05 inches and thickness of 0.0005 inches . the resultant illuminated vitrector has a diameter of 1.0 mm ( 0.5 mm fiberoptic light source + 0.5 mm 25-g vitrector ) [ fig . the assembly is sterilized with gamma radiation , ethylene oxide or cold gas sterilization . standard surgical technique with microvitreoretinal blade is used to create the sclerotomies.7 the posterior ppv is completed using a 20-g vitrector . at the end of the procedure the 20-g cutter is replaced with the 25-g illuminated curved vitrector [ fig . 3 ] . the illumination of the probe facilitates visualization of the vitreous on the opposite vitreous base ( 180 away ) , while the curved design of the probe avoids crystalline lens touch [ figs . 4 , 5 ] . this allows the surgeon to use the other hand to depress the opposite sclera , which enables viewing of the internal sclerotomy with its surrounding vitreous through the wide - angle lens system [ fig . position of the endoilluminator tip from the vitrector port can be varied by a gentle sliding maneuver during the surgery to optimize the illumination of the incarcerated vitreous . the vitreous incarcerated in the internal sclerotomy opening is shaved completely under direct visualization . excision of the peripheral vitreous in a phakic eye with a clear lens is one of the most challenging tasks in vitreoretinal surgery . with the advent of the wide - angle viewing systems , visualization of the peripheral vitreous base the potential of iatrogenic trauma to the posterior lens surface by the straight vitrectomy probe restricts access to the peripheral vitreous near the sclerotomy site.8 a curved instrument allows access to the internal sclerotomy site without damaging the posterior lens surface [ fig . 5].9,10 while using the curved or conventional vitrector , the surgeon holds the endoilluminator while the assistant depresses the sclera for view of the anterior vitreous . this makes the surgery assistant - dependent , time - consuming , and limits the dynamic viewing of the vitreous base with the endoilluminator . the 20-g curved illuminated vitrector addresses the problems of illumination of the peripheral vitreous and safety of the crystalline lens.11 however , it requires a larger sclerotomy ( 18-g ) than conventionally used , thereby increasing the risk of sclerotomy - related leakage and vitreous incarceration . due to the smaller diameter of the shaft , the 25-g curved illuminated vitrector allows removal of the vitreous from the internal sclerotomy site through a conventional sclerotomy ( 20-g ) while preserving the safety of the posterior lens surface . clinical examination as well as ultrasonographic examination confirmed this in both pseudophakic and phakic patients [ fig- 6a , b ] . an illuminated sleeve ( synergetics , inc . charles , mo ) that wraps around a straight 25-g vitrector provides the benefit of illuminated 25-g vitrector in a pseudophakic eye . however , the illuminated sleeve does not conform to the curved 25-g vitrector and can not be used in phakic eyes without risk of lens touch . effective and complete removal of vitreous from the internal sclerotomy prevents postoperative complications associated with wound healing . sabti et al . , studied 22 eyes with ultrasound biomicroscopy ( ubm ) of which 11 underwent ppv with complete shaving of the vitreous from the internal sclerotomy site by indentation with a straight conventional vitrector , while 11 eyes in the control group underwent conventional ppv only . complete vitreous shaving around the sclerotomy site significantly reduced vitreous incarceration.4 removal of vitreous from the internal sclerotomy assumes added importance during implantation of intra - vitreal drug delivery systems where large sclerotomies are necessary to accommodate the size of the implant ( 2 to 4 mm ) . in a prospective study utilizing ubm to study the internal sclerotomy site in diabetic patients undergoing vitrectomy , bhende et al . , noted that eyes with postoperative vitreous incarceration developed fibrovascular proliferation six months after surgery.3 this is a known high - risk factor for recurrent vitreous hemorrhage after ppv in diabetics we have successfully employed this instrument in 100 complicated vitreoretinal procedures , of which 41 were phakic eyes . no lens - related complications occurred , though novice surgeons may experience a learning curve with the new device . in summary , the 25-g curved illuminated cutter combines the advantage of a self - illuminated vitrectomy probe and custom curved design that avoids crystalline lens touch . in addition , its usage through a standard 20-g sclerotomy in facilitating complete removal of vitreous from the internal sclerotomy prevents sclerotomy - related complications .

incarceration of vitreous in sclerotomy sites during pars plana vitrectomy can lead to wound - related complications similar to vitreous incarceration in cataract surgery . we describe an illuminated curved 25-gauge vitrectomy probe for removing vitreous from sclerotomy sites . polyester tubing is used to secure a fiber optic endoilluminator ( 0.5 mm ) with the curved 25-gauge vitrector ( 0.5 mm ) . the resultant illuminated curved vitrector ( 20 g ) has a diameter of 1.0 mm . it facilitates complete removal of vitreous around the internal sclerotomies under direct visualization in both phakic and pseudophakic eyes . the same was confirmed with ultrasound biomicroscopy of the sclerotomy sites . curved vitrector reduces postoperative complications related to incarcerated vitreous in phakic and pseudophakic eyes and other sclerotomy - related wound complications .

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superficial siderosis of the central nervous system due to chronic , recurrent subarachnoid hemorrhage is a rare and potentially debilitating disorder . the classic manifestation is progressive bilateral sensorineural hearing loss , although ataxia and pyramidal signs also are common . in the largest review of literature to date , though the age of presentation ranges from 15 to 78 years , it is seen more commonly in patients above 40 years . . we hereby present a young boy with this disorder to emphasize its occurrence in children . a twelve - year - old boy presented to the neurology outpatient clinic with a history of intermittent holocranial headaches since two years and recent - onset blanking spells . the headaches were moderately severe , with no diurnal variation , occurring once in two weeks with no particular aggravating factor and subsiding with analgesic medication . however , at two years of age , he had developed sudden - onset vomiting , irritability , and imbalance which was progressive , not associated with fever , trauma , or varicella infection . over the subsequent month , he developed a divergent squint . a computed tomography of the brain revealed a mass lesion in the cerebellar vermis with supratentorial hydrocephalus . he underwent near - total excision of the tumor , with a thin rim of the tumor left behind . for the residual rim of tumor margin , he was subjected to external radiotherapy to the posterior fossa with 6 mv photons ( total dose being 5040cgy/28fr/54 days ) and was declared free of the disease subsequently . a magnetic resonance imaging ( mri ) of the brain was done which was normal except for postoperative changes ; hence , the headaches were treated with plain analgesics . over the next two years , he developed intermittent brief episodes of blanking spells , when he was referred to our center . a thorough neurological assessment revealed nystagmus , ataxia , and dysarthria with a normal tone . an electroencephalogram done for the blanking spells showed mild epileptiform abnormality and he was put on oxcarbamazepine . a repeat mri revealed cystic space in the posterior fossa ( as a result of the previous surgery ) and hypointensities around the cerebellar folia [ figure 1a ] . assessment of brainstem auditory evoked potentials confirmed bilateral mild sensorineural hearing loss . a repeat clinical assessment after six months showed significant deterioration in dysarthria and ataxia . a repeat mri after six months showed progression in the deposition of hemosiderin in the cerebellar folia from the previous one [ figure 1b ] . the clinical picture of a progressive worsening ataxia with sensorineural hearing loss along with the neuroimaging findings of the deposition of hemosiderin in the cerebellum clinches a diagnosis of superficial siderosis in this child , secondary to the surgery of the posterior fossa done in early childhood . ( a ) susceptibility weighted images showing hypointensities around the cerebellar folia , representing deposition of hemosiderin ( b ) imaging done after six months showed progressively increased deposition of hemosiderin nevertheless , the origin of superficial siderosis of the central nervous system remains undetermined in most cases . highly vascular spinal tumors , vascular abnormalities of the central nervous system , and surgical procedures of the posterior fossa are the most commonly identified sources of chronic bleeding . a past history of trauma and prior intradural surgery may be further risk factors . it is a distinct clinical syndrome characterized by sensorineural deafness ( 95% ) , cerebellar ataxia ( 88% ) , and pyramidal signs ( 76% ) . other features include dementia ( 24% ) , bladder disturbance ( 24% ) , anosmia ( at least 17% ) , anisocoria ( at least 10% ) , and sensory signs ( 13% ) . less frequent features are extraocular motor palsies , pain in the neck or back , bilateral sciatica , and lower motor neuron signs ( 5 - 10% each ) . in a case report by sevki et al . , headache was also quoted to be a presenting symptom . in our patient , headache was the main presenting complaint followed later by progressive ataxia and hearing loss . the pathogenesis of superficial siderosis involves recurrent subarachnoid hemorrhage resulting in the prolonged contact of these tissues with iron . within the cerebellum , the microglia as well as bergmann glia are uniquely sensitive to iron - mediated cell damage . the terminal processes of bergmann glia that interface with the subarachnoid space mediate iron uptake from the cerebrospinal fluid ( csf ) , inducing the synthesis of ferritin within these cells . because ferritin sequesters iron and is thus thought to play a role in iron detoxification , intracellular iron may not cause toxicity until ferritin biosynthesis is overwhelmed by a large iron load . excess free iron may then stimulate lipid peroxidation , leading to localized tissue necrosis . in the past , superficial siderosis was diagnosed almost exclusively at autopsy . with the advent of mr imaging mri has identified siderosis in reportedly asymptomatic patients . in one series , which examined 8,843 consecutive mri studies , however , he had clear signs of a progressive deficit on serial assessments . in most cases , the use of various therapies has been reported without a clearly discernible benefit , namely , steroids , iron chelators , selegiline , vitamin c , and other antioxidants . in cases where a source of chronic subarachnoid bleeding is identified , however , in about 25 - 40% of the patients , a source of siderosis is not identified , as in our patient , and treatment remains essentially symptomatic . to conclude , our case is unusual as the classical syndrome of superficial siderosis is seen at a young age , secondary to an early surgery of the posterior fossa .

superficial siderosis of the central nervous system results from deposition of hemosiderin in the subpial layers of the brain and spinal cord . patients usually present after 40 years of age with progressive ataxia and sensorineural hearing impairment . we present the case of a twelve - year - old boy who had a surgery of the posterior fossa at the age of two years and then developed recurrent headaches , instability of gait , and hearing deficit at around ten years of age . clinical examination revealed progressive ataxia and mild sensorineural hearing loss . he also had infrequent seizures with mild electroencephalographic abnormality . his serial magnetic resonance imaging ( mris ) showed a progressive deposition of hemosiderin in the cerebellar folia and around the brainstem , confirming a diagnosis of superficial siderosis . this case report draws attention to this rare condition , usually seen in adults , even though rarely it can be seen in children as a chronic sequela of surgery of the posterior fossa .

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acute promyelocytic leukemia ( apml ) is a subset of aml with characteristic clinical , morphological and genetic features . its incidence gradually increases , reaching a plateau during early adulthood , remaining constant until it diminishes after 60 years of age . the identification of specific chromosomal abnormality plays an important role in determining therapy and prognosis in certain subtypes of aml . data from the pediatric oncology group have shown that inv(16 ) / t(16;16 ) , t(8;21 ) , and normal karyotypes are associated with favorable prognostic outcome , whereas poorer outcome was observed in t(15;17 ) ( without all- trans retinoic acid ( atra ) treatment ) , 11q23 , and other abnormalities . , several specific recurrent chromosome aberrations have been described in aml , both unbalanced and balanced rearrangements . balanced chromosome rearrangements are detected in approximately 2530% of adults with de novo aml and have attracted a great deal of attention not only because their molecular dissection has led to identification of genes involved in leukemogenesis but also because specific translocations and inversions are associated with clinical features and treatment outcome of patients harboring them.[46 ] in this article , we discuss the case study of a two - year - old child with unbalanced chromosome aberrations involving chromosome 17 with a cytogenetically normal chromosome 15 . patient had a history of fever , general weakness and bleeding from the gums . on examination , his general condition was poor , with cervical and axillary lymph nodes . on systemic examination , he had hepatomegaly 23 cm , and splenomegaly 12 cm . at presentation , hemogram was hb 69 g / l , total count of 52 10/l and platelets 20 10/l . differential count showed neoplastic promyelocytes 80% , neutrophils 12% , lymphocytes 12% , bone marrow aspiration showed hyper cellular marrow with sheets of neoplastic promyelocytes ( 70 % ) . ( a ) peripheral smear : auer rods positive , ( b ) mpo positive cytogenetic study was carried out on cells from bone marrow aspiration . short - term culture of 24 and 48 h were set up using rpmi 1640 medium supplemented with 20% fetal bovine serum . after 1618 h , 50 l of colcemid at a final concentration of 10 g / ml was added for 30 min followed by hypotonic treatment , fixation in carnoy 's fixative . fifteen metaphases were analyzed which consistently showed 46xy , -17,+der(17)(17qter - cen-17q21 : ) karyotype [ figure 2 ] . short - term culture of 24 and 48 h were set up using rpmi 1640 medium supplemented with 20% fetal bovine serum . after 1618 h , 50 l of colcemid at a final concentration of 10 g / ml was added for 30 min followed by hypotonic treatment , fixation in carnoy 's fixative . fifteen metaphases were analyzed which consistently showed 46xy , -17,+der(17)(17qter - cen-17q21 : ) karyotype [ figure 2 ] . short - term culture of 24 and 48 h were set up using rpmi 1640 medium supplemented with 20% fetal bovine serum . after 1618 h , 50 l of colcemid at a final concentration of 10 g / ml was added for 30 min followed by hypotonic treatment , fixation in carnoy 's fixative . fifteen metaphases were analyzed which consistently showed 46xy , -17,+der(17)(17qter - cen-17q21 : ) karyotype [ figure 2 ] . to our knowledge , this is a rare cytogenetic abnormality in a child , involving only chromosome 17 . the first report of aml - m3 with normal chromosome 15 with -17 , ins(17 ; ? ) ( q11q21 ; ? ) was by baranger et al . the present case demonstrated normal appearance of chromosome 15s , while one of the 17 homologues appeared to be an iso ( 17q ) , but upon detailed examination showed break on one of the arms at q21 band . the presence of 15q+ and i(17q- ) is one of the most frequent abnormalities reported besides the standard translocation , but with an i(17q- ) and two normal chromosome 15 is extremely rare . routinely cytogenetics , fluorescence in situ hybridization ( fish ) , and polymerase chain reaction ( pcr ) analysis are employed for the diagnosis and precise localization of the fusion gene . but in our case , fish could not be performed and even before the cytogenetic results were available the patient died due to disseminated intravascular coagulation . hence , further molecular studies to establish the type of gene fusion transcript which could have had a prognostic value could not be ascertained . a small proportion of apml patients do not have t(15;17)/ pml - rara but do have other chromosomal aberrations and gene fusion , all these rearrangements and t(15;17 ) are very strongly correlated with characteristic marrow morphology in which abnormal promyelocytes predominate ( fab- m3 ) . the present who classification recognizes two main morphological subtypes of apml that includes a more frequent hyper granular variant form featured by abnormal dysplastic promyelocytes with abundant cytoplasmic granules and auer rods ( faggots ) and a less frequent micro granular variant of apml characterized by leukemic blast , bilobed nuclei with dusty and minute cytoplasmic granules . the evolution of aml involves leukemogenic events that occur in the stem cell ( stem cell origin model ) and favors self renewal while disrupting normal hematopoietic cell lineage development.[810 ]

acute myeloid leukemia ( aml - m3 ) is associated with the translocation t(15;17)(q22;q12 - 21 ) which disrupts the retinoic acid receptor alpha ( rara ) gene on chromosome 17 and the pml gene on chromosome 15 . we report a two - year - old patient with aml - m3 without the usual translocation t(15;17 ) . cytogenetic studies demonstrated normal appearance of chromosome 15 while the abnormal 17 homologue was apparently a derivative 17 , der(17)(17qter - cen - q21 : ) , the rearrangement distinctly shows deletion at 17q21 band and the morphology corresponding to an iso chromosome i(17q- ) . this case report is a rare cytogenetic presentation of acute promyelocytic leukemia ( apml ) .

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a 28-year - old woman , with primary infertility of three years was referred for laparoscopic myomectomy with a history of severe dysmenorrhea and a diagnosis of posterolateral wall myoma . on pelvic examination , a palpable myoma was noted on the posterior uterine surface , and the uterus was felt to be approximately 10 gestational weeks in size . a well - circumscribed mass measuring 5.16 6.0 4.25 cms was seen in the posterolateral fundus and was found to be impinging on the endometrial stripe . the patient was given a choice between conventional laparoscopic myomectomy and the single incision approach . a 2 cm vertical incision was made at the base of the umbilicus and peritoneal access was gained . , norwalk , ct ) , [ figure 1 ] was inserted through the incision . the device , made from an elastic polymer , was slightly hourglass shaped and could be deployed through 2 cm fascial incision . it contained four openings : one for insufflation via a right - angled tube and three that could accommodate trocars 5 to 12 mm in size . the compressibility of the elastic polymer allowed for the access ports to expand and form fit the space in which they resided , and the ports also passed through the working channels . the sils tm port has the capacity of up to three laparoscopic instruments of 5 to 12 mm after careful survey of the abdomen and pelvis , dilute vasopressin , 20 u , in 100 ml of saline solution , was injected subserosally over the posterior myoma . once the correct plane was entered , the myoma was dissected out of the uterus using a 5 mm myoma cork screw and blunt scissors . using mostly blunt dissection , the enucleation of the myoma was done [ figure 2 and 3 ] . hemostasis was ensured and a piece of adhesion barrier ( gynecare interceed ; ethicon inc . , west somerville , new jersey ) was then cut in half , introduced into the abdomen through one of the 5 mm trocars , and placed over the hysterotomy incision . the myoma was then grasped with a 12 mm claw forceps and electric morcellation was done using rotocut g1 morcellator morcellation ( rotacut ) the advantages obtained by electronic morcellation over manual morcellation from umbilical incision site are : reduction in operative timedecreased risk of hernia formation due to absence of tearing or stretching of fascialower risk of injury to the surrounding tissues . reduction in operative time decreased risk of hernia formation due to absence of tearing or stretching of fascia lower risk of injury to the surrounding tissues . as laparoscopic myomectomies are performed routinely in our center , rotocut is preferred over gynecare morcellex for its cost effectiveness and speed . it is reusable and can be used indefinitely with periodic replacement of the cutting blade . the fascia was closed with a running 0 polyglactin 910 ( vicryl , somerville , nj ) suture . the skin was then approximated with a series of interrupted 3/0 monocryl sutures ( ethicon inc . ) . ten milliliters of 0.5% bupivacaine hydrochloride ( sensorcaine ) were injected into the incision site , and dermabond adhesive ( ethicon inc . ) was applied . the total procedure time ( time from first incision to end of procedure , d and c ) single - incision surgery has been reported to offer patients improved cosmetic outcomes as compared to multiport laparoscopic surgery , and possibly less postoperative pain , although these potential benefits have yet to be demonstrated in a well - designed prospective trial . a number of advantages have been proposed including cosmesis , less incisional pain , less blood loss , and the ability to convert to standard multiport laparoscopic surgery . an additional morcellation port is avoided as specimen retrieval / morcellation can be done through the umbilical incision . the primary limitations of sils are the restricted degrees of freedom of movement , lack of triangulation , the number of ports that that can be used , and the proximity of the instruments to each other during the operation all of which increase the complexity and technical challenges of the operation . many of these difficulties may be related to the technique of port placement and utilization during single incision laparoscopic surgery . a number of methods have been described for port access to perform sils , including multiple fascial punctures through one skin incision and use of novel port access devices . to further overcome the technical challenges of sils , different instruments that provide angulations and small profile trocars , endostitch , are being developed . the barbed suture greatly facilitates myometrial closure because there is no need to tie knots and there is no backsliding of the suture , which enables continuous wound closure with even distribution of tensile strength throughout the repair . these benefits of barbed suture are especially valuable in single - incision surgery , because intracorporeal knot tying can be more challenging here than in the multiport approach . currently , careful case selection is paramount , so that these procedures can be explored safely , with a low threshold to convert to standard laparoscopy , as indicated , for safety and quality of care . the use of novel port access devices , articulated instruments , and endostitch self - retaining sutures , makes the procedure easier , with a potential for saving time .

single port laparoscopic surgery ( spls ) , also called sils is the natural extension of multi - incisional laparoscopic surgery , in the quest for reduction of traumatic insult and residual scarring to the patient . today with the evolution of newer instruments , bidirectional self - retaining sutures , and surgical experience we are able to perform many surgeries in gynecology .

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we describe the restructuring that is taking place in primary health care ( phc ) in portugal and discuss how the new emerging organization and work practices reflect in care transitions and intra- and inter - organizational integration . phc represents an essential support for the restructuring that is taking place in health care in portugal . we conducted a case study on a health centre located in the centre region of portugal . health centres are reorganizing toward a new model characterized by an organizational structure based on functional units : family health unit ( fhu ) , community care unit ( ccu ) , and personalized healthcare unit ( phu ) , which will be in place in all of them plus transversal units , common to a group of these arrangements . the overarch management body is the aces ( agrupamento de centros de sade ) , that reports to a health regional administration ( hra ) . in portugal , there are five hra . an aces may coordinate a number of fhu , ccu and phu but has only one public health unit and one shared resources care unit . units are based on multidisciplinary teamwork , having : specific missions , although inter - cooperative and complementary , organized in a network ; administrative autonomy ; proper instruments of organizational management ; well - defined leadership and clinical governance systems and mechanisms of representation and participation of the community and citizens . it is too soon to assess the implications that the reorganization of phc might have in the integration of care in portugal .

introductionwe describe the restructuring that is taking place in primary health care ( phc ) in portugal and discuss how the new emerging organization and work practices reflect in care transitions and intra- and inter - organizational integration.theory and methodsphc represents an essential support for the restructuring that is taking place in health care in portugal . we conducted a case study on a health centre located in the centre region of portugal . we identified and analyzed internal units and care transitions and conducted interviews.resultshealth centres are reorganizing toward a new model characterized by an organizational structure based on functional units : family health unit ( fhu ) , community care unit ( ccu ) , and personalized healthcare unit ( phu ) , which will be in place in all of them plus transversal units , common to a group of these arrangements . the overarch management body is the aces ( agrupamento de centros de sade ) , that reports to a health regional administration ( hra ) . in portugal , there are five hra . an aces may coordinate a number of fhu , ccu and phu but has only one public health unit and one shared resources care unit . units are based on multidisciplinary teamwork , having : specific missions , although inter - cooperative and complementary , organized in a network ; administrative autonomy ; proper instruments of organizational management ; well - defined leadership and clinical governance systems and mechanisms of representation and participation of the community and citizens.conclusions and discussionit is too soon to assess the implications that the reorganization of phc might have in the integration of care in portugal .

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supplementary material is available for this article at 10.1007/s13659 - 012 - 0038 - 8 and is accessible for authorized users .

three new triterpenoids , 3-hydroxy - urs-30-p - z - hydroxycinnamoyl-12-en-28-oic - acid ( 1 ) , 3-hydroxy - olean-30-p - ehydroxycinnamoyl-12-en-28-oic - acid ( 2 ) and 3,6-dihydroxy - urs-14-en-12-one ( 3 ) , together with seven known triterpenoids , were isolated from the roots of rubia schumanniana . their structures were established by means of spectroscopic analysis . all compounds were evaluated for cytotoxic activity , and compounds 26 showed cytotoxicity with the ic50 values of 10.7518.87 g / ml . electronic supplementary materialsupplementary material is available for this article at 10.1007/s13659 - 012 - 0038 - 8 and is accessible for authorized users .

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several cell lines were isolated during independent experiments from dissected annulus fibrosus ( af ) tissue of mature bovine intervertebral discs ( ivd ) via a reproducible non - enzyme driven protocol . the cell lines were frozen at low passage number and they recovered well after freeze - thawing ( see fig . preliminary characterization of the af cells was carried out with bovine specific rna probes derived from bovine genomic dna using plate rna in situ hybridisation ( pish ) for col1a1 and col2a1 expression , two structural proteins found in the mature ivd . less type - ii collagen fibers were described for the outer af in rabbit correlating with a common notion that type ii collagen is higher in the np than the af , . the dissected outer af of mature bovine ivds was the source for our af cell lines and we did not detect col2a1 expression by either rna in situ hybridization ( sish ) , , , on sections of the outer af tissue or by pish on the cells derived from the outer af , while col2a1 expression was very prominent in cells of the np as shown by sish on the same section ( fig . the discrepancy between our findings and that of increased col2a1 expression in the bovine af over the np reported by minoque et al . might reflect differences in defining the af . we see col1a1 expression in af and np cells by sish in vivo and by pish in vitro ( fig . skinned bovine tails were collected fresh from local abattoirs , remained chilled and were processed within 2 h. tail pieces were immersed in 10% povidone - iodine solution , rinsed with tap water , followed by immersion in 70% etoh prior to removing all fat and muscle tissue . ivds were dissected away from adjacent vertebrae endplates , briefly dipped in 70% etoh and rinsed with 1 pbs/10% gentamicin prior to separating the outer af from the remaining ivd tissue . outer af tissue was cut into smaller pieces using sterile procedures and placed in uncoated as well as 0.1% gelatin coated 35 mm culture dishes ( falcon ) . sterile filtered fbs - hi with 10% gentamicin and 5 g / ml amphotericin b ( all gibco ) was added prior to the incubation at 37c , 5% co2 and atmospheric o2 . after 24 h the fbs mix was diluted 1:1 with standard dmem based growth medium containing 1 dmem with 4.5 g / l glucose , 1 pyruvate , 1 glutamax , 1 nonessential amino acids , 10% v / v hi - fbs , 0.48% v / v gentamicin ( all gibco ) , 0.12 mm beta - mercapthoethanol ( sigma ) and additional 5 g / ml amphotericin b and the tissue . following 48 h of incubation cells had attached to the bottom of the wells and were expanded in fresh standard dmem based growth medium ( see above ) . cell lines derived in such manner from af tissue could be passaged with 0.05% trypsin / edta ( gibco ) at 1:10 dilutions for more than 10 passages without slowing down in population growth or dramatic changes in morphology ( fig . early and late passages were subjected to plate rna in situ hybridization ( pish ) for preliminary gene expression analysis ( fig . during embryogenesis , the af part of the ivd is believed to be of sclerotomal origin , . cultured cells derived from the outer af of mature bovine caudal ivds with our procedure were assayed for the expression of two major collagen genes col1a1 and col2a1 . the observed in vitro expression of these two genes mirrored the in vivo expression in cells of the mature the af : presence of col1a1 expression and absence of col2a1 expression in cells of the outer af ( fig .

the adult bovine ( bos taurus ) intervertebral disc is primarily comprised of two major tissue types : the outer annulus fibrosus ( af ) and the central nucleus pulposus ( np ) . we isolated several primary cell lineages of passage ( p ) 0 cells from the af tissue omitting typically used enzymatic tissue digestion protocols . the cells grow past p10 without signs of senescence in dmem + 10% fcs on 0.1% gelatin coated / uncoated surfaces of standard cell culture plates and survive freeze - thawing . preliminary analysis of the af derived cells for expression of the two structural genes col1a1 and col2a1 was performed by pish recapitulating the expression observed in vivo .

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to describe a case of choroidal neovascularization ( cnv ) following photorefractive keratectomy ( prk ) to correct myopia . we performed prk in both eyes of a 20-year - old girl to correct myopia . refractive error was 4.75 2.25 5 in the right eye and 5.00 1.25 180 in the left eye . metamorphopsia was noticed by the patient in the right eye one month after the surgical procedure . fluorescein angiography and optical coherence tomography ( oct ) were performed which were compatible with cnv . after three monthly intravitreal bevacizumab injections , sub - retinal hemorrhage and intraretinal fluid resolved , but subretinal scar remained without any visual acuity improvement . also , refractive surgeons should consider cnv development in cases with visual compliant or metamorphopsia following prk . there are some reports of cnv after laser in situ keratomileusis ( lasik ) surgery , but to our knowledge , only one case of cnv following prk has been reported . here prk was performed in both eyes of a 20-year - old girl to correct myopia . the procedure was performed at refractive surgery center of baqiyatallah hospital , tehran , iran . a preoperative examination including refraction and best corrected visual acuity ( bcva ) measurements , slit - lamp examination , intraocular pressure ( iop ) measurement , and fundoscopy with dilated pupil was performed by the surgeon and reported as normal . preoperative refractive error was 4.75 2.25 5 and 5.00 1.25 180 in the right and left eye , respectively . alcohol - assisted corneal epithelium debridement was done , and mitomycin c was used at the end of the procedure . one month after surgical procedure , metamorphopsia developed in the right eye , and visual acuity reduction happened 3 months later . the patient was referred to retina clinic of the baqiyatallah hospital , tehran , iran 4 months after prk . on fundus examination there was an area of subretinal hemorrhage in the para foveal area associated with macular edema of the right eye . fluorescein angiography showed para foveal leakage ( fig . 1 ) , and optical coherence tomography ( oct ) revealed a hyper - reflective sub - retinal material associated with intraretinal fluid and pigment epithelial detachment ( fig . although the effect of intravitreal anti vascular endothelial growth factor ( anti - vegfs ) in the cases of cnv following excimer laser refractive surgery has not been completely understood , we used 1.25 mg intravitreal bevacizumab ( avastin ; genetech inc , south san francisco , california , usa ) for treatment . after 3 monthly intravitreal injections , sub - retinal hemorrhage resolved and intraretinal fluid improved , but sub - retinal scar developed ( fig . 3a and b ) . one month after the 3rd intravitreal injection , the bcva was 20/400 , and no visual acuity improvement was observed . high myopia has been reported as a major cause of cnv formation ( 62% ) in young patients . in the present report neo et al reported 3 cases of unilateral cnv after lasik for high myopia . among their patients , the mean spherical equivalent was 11.42 d ( range from 6.75 to 20.00 d ) . they used a combination of intravitreal ranibizumab and photodynamic therapy ( pdt ) with verteporfin for the treatment . the mean bcva was 0.44 logmar and 0.17 logmar at presentation and after treatment , respectively . saeed et al described a case of cnv after lasik for correction of low myopia . the refractive error in their patient was 2.75 d in both eyes , and cnv developed in one eye 3 months after surgery . although loewenstein et al described macular hemorrhage in three patients with high myopia ( 13.00 to 20 d ) after prk , to date , there has only been one report of cnv after prk . ruiz - mareno and colleagues evaluated the incidence of cnv in 5963 eyes undergoing prk for the correction of myopia . cnv developed in one eye after correction of 12.00 d of myopia 26 months after prk . the same researchers reported one case of cnv after the same number of prk surgeries . progressive elongation of the axial length and degenerative changes of the choroid in highly myopic eyes may cause the linear breaks in bruch 's membrane which are called lacquer cracks . lacquer cracks may be related to development of cnv.9 , 10 myopic changes and lacquer cracks were not observed in the fundus examination of our case . iop elevation induced during lasik surgery may result in posterior segment pathologies and may be a factor for cnv formation . iop elevation does not happen during prk , and this may be the cause of lower reports of cnv formation following prk compared with lasik . acoustic shock waves produced by the excimer laser are another factor proposed to play a role in the cnv formation after both prk and lasik . cnv is not common in a 20-year - old patient without obvious myopic chorioretinal changes and lacquer cracks . also , our patients visual symptoms developed only 1 month after prk surgery . therefore , prk may play a role in the development of cnv in our case . since idiopathic and myopic cnv can not be ruled out in our case , the cause - and - effect relationship between the surgical procedure and cnv formation is not established . in conclusion also , refractive surgeons should consider cnv development in cases with visual compliant or metamorphopsia following prk .

purposeto describe a case of choroidal neovascularization ( cnv ) following photorefractive keratectomy ( prk ) to correct myopia.methodswe performed prk in both eyes of a 20-year - old girl to correct myopia . refractive error was 4.75 2.25 5 in the right eye and 5.00 1.25 180 in the left eye.metamorphopsia was noticed by the patient in the right eye one month after the surgical procedure . the patient was referred 3 months later when visual loss happened.resultsfluorescein angiography and optical coherence tomography ( oct ) were performed which were compatible with cnv.after three monthly intravitreal bevacizumab injections , sub - retinal hemorrhage and intraretinal fluid resolved , but subretinal scar remained without any visual acuity improvement.conclusionsit seems that cnv may occur after prk in myopic eyes . also , refractive surgeons should consider cnv development in cases with visual compliant or metamorphopsia following prk .

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a 52-year - old thai woman presented with asymptomatic annular erythematous plaques on the forehead and both cheeks that persisted for 2 years . dermatologic examination showed few discrete annular erythematous plaques on her forehead and both cheeks , 15 cm in diameter . there were solar lentigines and telangiectasias on the malar area , nose , and forehead as shown in fig . 1 and fig the routine histopathology demonstrated nodular and interstitial inflammatory cell infiltrate of histiocytes intermingled with some lymphocytes in the dermis as shown in fig . elastic stain showed elastotic material phagoticized by multinucleated cells and marked decrease of elastic tissue in some foci of the affected dermis ( fig . 4 ) . according to the clinical and histopathological findings , the dermatologic diagnosis was actinic granuloma ( ag ) . complete blood count , liver enzyme , fasting blood glucose , and glycated hemoglobin were within normal range . the patient 's dermatologic condition was treated with prednisolone 15 mg / day for 6 weeks with a good response currently , she has been treated with hydroxychloroquine ( 200 mg / day ) , topical 0.1% mometasone furoate cream , broad spectrum sunscreen , and sun avoidance with partial improvement . it was also termed annular elastolytic giant cell granuloma , atypical necrobiosis lipoidica of the face and scalp , miescher 's granuloma of the face , and granuloma multiforme [ 1 , 2 , 3 , 4 ] . ultraviolet ( uv ) radiation , especially uva , and heat are recognized as causal factors , by changing the antigenicity of elastic fibers . the immune response mediated by helper t cells to degenerated elastic tissue the typical cutaneous lesion of ag is an initially smooth , elevated , nonscaly , erythematous papule which centrifugally extends to an annular plaque with central clearing . they are usually distributed on chronically sun - exposed areas such as the face , neck , upper back , forearms , and dorsum of the hands . apart from the skin , conjunctival involvement has been reported in a few cases [ 6 , 7 ] . there are some reports on the association between ag and internal diseases such as hematologic and solid malignancy , monoclonal gammopathy , temporal arteritis , erythema nodosum , and x - linked dominant protoporphyria [ 8 , 9 , 10 , 11 ] . diabetes mellitus has been found in about 3740% of patient with ag , and may be caused by injury of elastic fiber from hyperglycemic state . as for the renal condition , focal segmental glomerulosclerosis has been described in association with various granulomatous diseases ( e.g. , sarcoidosis , wegener 's granulomatosis , churg - strauss syndrome , and kimura 's disease ) [ 13 , 14 , 15 , 16 ] . these include granuloma annulare , erythema annulare centrifugum , annular lichen planus , secondary syphilis , necrobiosis lipoidica , tinea corporis , and tuberculoid leprosy . the best method to obtain a precise histopathology is an elliptical biopsy across the annular rim and stained with elastic van gieson to demonstrate the three zones of elastic tissue change . in the first zone , solar elastosis is identified in the surrounding unaffected skin . in the second zone , a granulomatous reaction consisting of histiocytes and foreign - body type multinucleated cells is seen , with engulfment of elastotic fibers , representing the annular rim . in the third zone , an absence of elastic tissue in the superficial dermis is found in the center of the plaque . due to aesthetic concern in our case topical corticosteroids , intralesional corticosteroids , systemic corticosteroids , topical calcineurin inhibitors , phototherapy and photochemotherapy ( narrowband uvb , puva , re - puva ) have been used with some benefit [ 18 , 19 , 20 ] . cyclosporine a , dapsone , pentoxifylline , isotretinoin , and acitretin have been reported to be effective in some cases [ 21 , 22 , 23 ] . there are a few case reports with positive results from antimalarial therapy ( chloroquine and hydroxychloroquine ) . to prevent the development of new lesions , patients should be instructed to avoid sun exposure and regularly use sunscreen . our patient had good response to a short course of low - dose prednisolone . however , rapid relapse occurred after the treatment was discontinued . currently , she has been treated with hydroxychloroquine ( 200 mg / day ) , topical 0.1% mometasone furoate cream , broad spectrum sunscreen , and sun avoidance with partial improvement . to the best of our knowledge , the correlation between ag and focal segmental glomerulosclerosis is still unidentified , further investigation is needed to establish the relationship between these two conditions . the authors declare no conflicts of interest . there was no funding for this work .

actinic granuloma is an uncommon granulomatous disease , characterized by annular erythematous plaque with central clearing predominately located on sun - damaged skin . the pathogenesis is not well understood , ultraviolet radiation is recognized as precipitating factor . we report a case of a 52-year - old woman who presented with asymptomatic annular erythematous plaques on the forehead and both cheeks persisting for 2 years . the clinical presentation and histopathologic findings support the diagnosis of actinic granuloma . during that period of time , she also developed focal segmental glomerulosclerosis . the association between actinic granuloma and focal segmental glomerulosclerosis needs to be clarified by further studies .

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rupture of intervertebral disc material into the intradural space is a rare event in lumbar disc disease but must be considered in the differential diagnosis of mass lesion causing nerve root or cauda equina syndromes . the pathogenesis of lumbar intradural disc herniation is most likely related to dense adhesion between the ventral dura mater and the posterior longitudinal ligament . intradural disc herniations are usually seen at l4-l5 and l3-l4 , but have also been reported at other levels . there are approximately nine reports in the english literature of intraradicular disc herniation at l5-s1 . however , intradural disc herniation at l5-s1 is quite rare . this report presents a case of intradural disc herniation at l5-s1 mimicking an intradural extramedullary spinal tumor . a 61-yr - old man was admitted to hospital having experienced pain in the lower back and both lower legs for 4 months and a sudden exacerbation of the symptoms for 3 days before admission . neurological examination revealed weakness of the extensor hallucis longus and decreased ankle reflex in both lower extremities . a sensory deficit over the saddle area was observed , but bladder and bowel function were normal . magnetic resonance imaging ( mri ) showed a mass - like lesion at the level of l5-s1 space ( fig . 1 ) . gadolinium - enhanced mri demonstrated a large disc herniation at the l5-s1 level with an intradural component ( fig . subsequent durotomy demonstrated a 12 cm mass occupying the spinal canal with peripheral displacement of the nerve roots ( fig . careful excision of the disc fragment revealed a 0.40.4 cm defect in the anterior thecal sac , which was firmly adherent . the patient 's postoperative period was uneventful and he gained full recovery in 3 months . intradural disc herniations comprise 0.27% of all herniated intradural disc herniation at l5-s1 discs ( 1 ) . lumbar intradural disc rupture must be considered in the differential diagnosis of mass lesions causing nerve root or cauda equina syndromes . approximately 123 cases of intradural disc herniations have been reported since 1942 ( 2 ) . the majority of them occurred at the l4-l5 levels and only 12 cases occurred at l5-s1 . type b : herniation of a disc into the dural sheath in the preganglionic region of the nerve root . this terminology is confusing and actually indicates a special type of disc herniation through the dural sheath of the nerve root but not within the epineurium . therefore , describing type b as an intraradicular disc herniation is more specific and certain . type b intradural disc herniations are much less frequent . of the 12 cases of intradural disc herniation were reported at l5-s1 , 9 belonged to type b intradural disc herniation and the other 3 could not be classified due to the absence of any comment of their type . ten cases of type b intradural disc herniation have been reported , and all were in the lumbar region : 9 in the s1 nerve root and one in the l5 nerve root ( 3 - 6 ) . there are approximately nine reports in the english literature of intraradicular disc herniation at l5-s1 . this report presents a case of type a intradural disc herniation at l5-s1 mimicking an intradural extramedullary spinal tumor . the exact mechanism of the dural tear by a herniated disc is not known clearly . an anatomical investigation revealed dense non - separable adhesions of the ventral dura to the posterior longitudinal ligament at the l4-l5 level in eight of 40 cadavers ( 7 ) . it was suggested that adhesions formed congenitally or caused by trauma , surgery , inflammation , osteophytes or disc protrusion fixed the dural sac . a study of fresh adult cadavers by spencer et al . ( 8) demonstrated the existence of dural ligaments fixing the dura and nerve roots at their exit from the main dural sac to the posterior longitudinal ligament and vertebral body periosteum proximal to the intervertebral disc . distal fixation generally occurs at the intervertebral foramen where the epineural sheath of the spinal nerve is attached . these ligaments in certain cases also cause increased nerve root fixation , thereby allowing penetration of a ruptured disc to the s1 root . the reason why type a herniations occur at the l4-l5 intervertebral disc space and type b at l5-s1 is also yet be elucidated . the postulated mechanism is adhesions in both type a and type b. although intraradicular disc herniation are frequently seen at the l5-s1 , type a intradural disc herniation could occur at the l5-s1 , if adhesions between the ventral dura and the posterior longitudinal ligament are formed congenitally or caused by trauma , surgery , inflammation at the l5-s1 level . it is usually not difficult with current mri techniques to differentiate lumbar disc herniation from other conditions ( 2 ) . contrast - enhanced mri scans are useful to differentiate a herniated disc from a disc space infection or tumor . a herniated disc fragment will rarely be enhanced centrally , which is attributed to vascular granulation tissue infiltrating the fragment ( 2 ) . in our case , the lesion had intermediate signal intensity on t1-weighted and low signal intensity on t2-weighted mri scans and that led us to suspect an intradural extramedullary tumor lesion . however on contrast mri scans there was peripheral enhancement of the lesion , which is typical for a disc fragment ( 9 ) . while treating lumbar disc disease , the possibility of an intradural disc herniation should be kept in mind for the success of the discectomy and the management of failed back syndrome . we herein present a case of intradural disc herniation at l5-s1 mimicking an intradural extramedullary spinal tumor that demonstrates the role and the importance of contrast mri in the diagnosis of intradural disc herniation .

intradural lumbar disc herniation is a rare pathological entity . the pathogenesis of intradural lumbar disc herniation is not known clearly . intradural disc herniations usually occurred at the l4-l5 levels but have also been reported at other levels . however , intradural disc herniation at l5-s1 is quite rare . there are approximately nine reports in the english literature of intraradicular disc herniation at l5-s1 . we described a 61-yr - old man with suspected intradural mass at the level of l5-s1 space . the patient presented with pain in the lower back and both lower legs for 4 months and a sudden exacerbation of the symptoms for 3 days . gadolinium - enhanced magnetic resonance imaging ( mri ) demonstrated a large disc herniation at the l5-s1 level with an intradural component . l5 and s1 laminectomy was performed , and dura was swollen and immobile . subsequent durotomy was performed and an intradural disc fragment was removed . the patient had full recovery in 3 months . intradural lumbar disc herniation must be considered in the differential diagnosis of mass lesions in the spinal canal . contrast - enhanced mri scans are useful to differentiate a herniated disc from a disc space infection or tumor .

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a 59-year - old asymptomatic diabetic male was referred to our retinal service with presumed diagnosis of asteroid hyalosis . the patient had undergone laser treatment and intravitreal preserved triamcinolone acetonide injection for clinically significant diabetic macular edema in the right eye 4 years previously . the right eye showed focal laser scars in the macula and several shiny refractile crystalline deposits [ fig . 1 ] . optical coherence tomography localized these deposits to the posterior hyaloid [ fig . 2 ] . these deposits were isofluorescent and not associated with specific angiographic abnormalities [ fig . 3 ] . the patient has been followed for two additional years without any change in the visual acuity or status of the macula . although a posterior vitreous separation has not developed , the crystals have been observed to migrate slowly in distribution . a fundus photograph of the right eye demonstrating small pre - retinal crystals concentrated in the macula , although peripheral crystals are noted ( arrow ) para - foveal optical coherence tomography scan of the right eye demonstrating triamcinolone crystal deposits on the posterior hyaloid surface ( arrow ) fluorescein angiogram of the right eye revealing several micro - aneurysms and focal laser scars , but no crystals , which are isofluorescent triamcinolone has been shown to aggregate into crystalline structures that may resist the washout process and accumulate over the macula . a recent study has identified intra - vitreal triamcinolone acetonide injections , both preserved and preservative - free , as a cause of crystalline retinal deposits . our case report also identifies triamcinolone crystal deposition , all on the posterior hyaloidal surface . with follow - up now extending greater than 6 years , no functional toxic effects have been noted in our patient . whether the crystals retain any biological activity is unclear . in our case and the previous series no adverse visual effect or we suggest the term drug - induced benign hyaloidopathy and recommend this to be included as a differential diagnosis of crystalline maculopathy and asteroid hyalosis .

we report a case of unusually long persistence of triamcinolone crystals after intra - vitreal injection . crystals were noted on fundus examination predominantly confined to the posterior pole . optical coherence tomography localized the crystals to the posterior hyaloidal surface . over 6 years of follow - up the patient has retained good visual acuity and no observable changes in the retina . as the condition clinically resembles both crystalline maculopathy and asteroid hyalosis , we suggest the term drug - induced benign crystalline hyaloidopathy.

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the 2010 human influenza a ( h1n1 ) virus pandemic seriously affected many countries , including kuwait . in children , respiratory involvement usually occurs with h1n1 ; extra pulmonary problems are not common.1 liver involvement is rare and needs early identification and treatment . a 9-year - old child was admitted with intermittent low - grade fever , cough , vomiting , and abdominal pain lasting for one week . he received oral antibiotics ; the fever subsided initially but reappeared after a few days , along with jaundice . he was previously healthy , with no past history of liver disease . on examination , he was alert and oriented , his temperature was 39c , he was icteric , appeared toxic , was sweating , had a respiratory rate of 30 breaths / minute , and had congested tonsils ; a respiratory system exam showed prolonged expiration with expiratory rhonchi . there were no signs of meningeal irritation , and the rest of his physical examination was unremarkable . investigations revealed a hemoglobin ( hb ) count of 14.5 g / dl , a total leukocyte count of 3.37 10 , neutrophils 19% , lymphocytes 68% , a platelet count of 255 10 . urinalysis showed mild urobilinogen and ketones , but a urine culture was sterile after 48 hours of incubation . mmol / l , alanine amino - transferase was 1763 u / l , aspartate amino - transferase was 1871 units / l , alkaline phosphatase was 246 units / l , and gamma glutamyl transferase was 107 units / l . g / l , serum ammonia count 74 mmol / l , and serum lactate 2.06 mmol / l . the patient had normal serum amylase and lipase levels , a negative cold agglutinin test , a normal ultrasound of the abdomen , and a negative chest x - ray . nasal and throat swabs for h1n1 were positive by a reverse transcription polymerase chain reaction ( pcr ) test . a hepatitis a , b , and c serological screen was negative , and his serum acetaminophen level was normal . furthermore , an additional work - up to rule out other causes of fulminant liver failure was performed , including negative blood tests for herpes simplex virus pcr , adenovirus pcr , epstein his immunoglobulins ( igg , igm , and iga ) were within normal limits ; he also had a negative antinuclear antibody ( ana ) < 1:40 titer and a negative anti - smooth muscle antibody and anti - liver kidney microsomal antibody ( anti - lkm ) , ruling out the possibility of autoimmune hepatitis . finally , his serum amino acid and urine organic acids were unremarkable . he was treated according to centers for disease control and prevention ( cdc ) guidelines2,3 with tamiflu ( oseltamivir ; genentech , san francisco , ca ) for five days and other supportive measures , including fresh frozen plasma , iv - administered vitamin k , lactulose , and prophylactic intravenous antibiotics . severe infection is characterized by pneumonia , sepsis , septic shock , and multi - organ failure . extra - pulmonary involvement is rare in uncomplicated human infections.1 studies of mouse models suggest multiple organ localization , including the lungs , heart , thymus , liver , and spleen.4 snchez - torrent et al reported h1n1 encephalitis in a 3-month - old infant from spain.5 hepatic involvement is not frequent and accounts for less than 3% of all cases.1 carrillo - esper et al , in 2010 , reported two adult h1n1 patients with hepatic involvement.1 el - shabrawi et al , in 2011 , reported a 10-month - old child with acute myocarditis and fulminant hepatic failure associated with h1n1.6 the subject of the current case report had acute hepatic failure that presented as jaundice , elevated liver enzymes , and coagulopathy . most of the other causes of liver failure had been ruled out by relevant investigations . he responded well to antiviral and other supportive treatment , and showed full clinical and laboratory recovery . no viral replication is needed to produce hepatic damage , as there is evidence of hepatic oxidative stress and a decrease in antioxidant defenses even when the virus is isolated only from the lungs . this might be explained by the production of pro - inflammatory cytokines in the respiratory airway that leads to changes in hepatic metabolism and enzymatic activities.7,8 even though hepatic complications are rare in pediatric h1n1 cases , in reporting this case we would like to draw the attention of pediatric health care professionals to the importance of early recognition , focused investigations , diagnosis , and treatment of complicated human h1n1 infection .

liver involvement in pediatric influenza a ( h1n1 ) infection is rare . focused clinical evaluation and laboratory tests can rule out or identify hepatic complications early on . here we report on a 9-year - old boy treated by the gastroenterology , hepatology , and nutrition unit of al - adan hospital s pediatric department . the patient , who was infected with h1n1 during the 2010 pandemic , showed symptoms of associated acute hepatic failure , was managed conservatively , and recovered completely following treatment . the author would like to draw the attention of pediatricians to the hepatic aspect of human h1n1 infection in order for them to recognize it early and treat it in a timely manner .

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henoch - schonlein purpura is one of the most common types of vasculitis in children . henoch - schonlein purpura ( hsp ) is one of the most common types of vasculitis in children . it is a multisystem disorder that involves various joints and organs , and results from a leukocytoclastic vasculitis of small vessels . the characteristic clinical manifestations include non - thrombocytopenic purpura , arthritis or arthralgia , abdominal pain , gastrointestinal hemorrhage and renal abnormalities . although patients with hsp are in a pro - thrombotic state , thrombosis is a rare complication , with only eight previously reported cases of hsp - associated thrombosis in the literature . however , thrombosis is a potentially life - threatening condition , and clinicians should have a high index of suspicion for high - risk patients . here , we present a single case of hsp accompanied by a superior mesenteric vein ( smv ) thrombosis . a 14-year - old boy with no significant past medical or family history was admitted to our hospital complaining of abdominal pain for the previous 14 days . he had passed dark red and black stool for 7 days , and had an erythematous rash over the anterior aspect of the lower legs for 2 days with a day of bilateral ankle arthralgia . on general examination , his vital signs were stable and he had a palpable purpuric rash that predominantly affected the anterior aspect of his lower legs [ figure 1 ] ; the bilateral ankles were swollen . palpable purpuric rash on the legs the laboratory results were as follows : hemoglobin level : 14.5 g / dl ; leucocyte count : 25.27 10/l with 81% polymorphonuclear leukocytes ; lymphocyte count : 13% ; platelet count : 492/mm . serum electrolytes , blood urea nitrogen and creatinine , liver function tests , urine analysis , erythrocyte sedimentation rate , antinuclear antibody and anticardiolipin antibody levels and the coagulation profile were all within their normal ranges . an abdominal computed tomography ( ct ) scan showed thickening of the proximal small intestinal wall with a peritoneal effusion . the mesenteric ct venography was reported as a suspected smv thrombosis with edema of the proximal intestinal wall [ figure 2 ] . mesenteric ct venography revealed heterogeneous contrast within the superior mesenteric vein with a suspected filling defect within the lumen ( arrow ) . a thickened and blurred intestinal wall ( arrowheads ) as a result of edema was observed within the affected segments according to the clinical manifestations , laboratory results and radiological findings , the patient was diagnosed with hsp and suspected smv thrombosis . after 7 days , his abdominal pain resolved and a repeated abdominal ct scan revealed that the intestinal wall edema and peritoneal accumulation had improved . on the 10 day of hospitalization , follow - up ct venography revealed homogeneous contrast throughout the smv and no signs of venous thrombosis [ figure 3 ] . the pat ient had no abdominal pain , no new rash and no swollen joints . he was discharged from hospital on the 12 day of admission . during the 2-month follow - up period , he had no new complaints . homogenous contrast was observed within the superior mesenteric vein ( arrow ) , and the intestinal wall was even and well - demarcated ( arrowheads ) venous and arterial thromboses are rare but potentially life - threatening complications in patients with hsp . we conducted a review of the published literature and found eight other patients with hsp - associated thrombosis [ table 1 ] . the outcomes were good and most patients had no episode of relapse . reported cases of hsp associated with thrombosis hyperactivation of the coagulation system is a common phenomenon along with the impaired activation of the fibrinolytic system in hsp . after prompt treatment with anti - inflammatories and anticoagulation , the symptoms and signs of hsp improved in our case . so the follow - up ct venography showed no signs of thrombosis in the smv . the seventh reported case showed that a high level of plasma factor viii and homocysteine could be a risk factor for thrombosis . higher levels of homocysteine , which could be induced by endothelial injury associated with vasculitis , can cause hypercoagulability in patients with hsp . furthermore , levels of von willebrand factor ( vwf ) antigen , a marker of endothelial injury , are also elevated during the acute stage of hsp . factor viii , homocysteine and vwf antigen could be important risk markers that indicate patients at a higher risk of thrombosis . two other reported cases that showed hsp was associated with antiphospholipid syndrome ( apa ) , which can present with thrombosis . antiphospholipid antibodies can produce a procoagulant state by affecting the function of phospholipid binding proteins that are involved in the coagulation cascade . the combined effect of hsp and apa would cause a greater risk of arterial or venous thrombosis . in one further case hsp - associated thrombosis occurred in the context of behet 's disease , another form of vasculitis . it is likely that endothelial dysfunction combined with a hypercoagulable state could contribute to thrombosis . thrombosis is comparatively rare in hsp patients , but physicians should pay close attention to patients at a higher risk of developing thrombosis as a consequence of its potentially life - threatening outcomes . thrombosis is a rare complication , with only eight previously reported cases of hsp - associated thrombosis .

henoch - schonlein purpura ( hsp ) is one of the most common types of vasculitis in children . the characteristic clinical manifestations include non - thrombocytopenic purpura , arthritis or arthralgia , abdominal pain , gastrointestinal hemorrhage and renal abnormalities . thrombosis has been reported as , a rare complication of hsp . we present the case of a 14-year - old boy who was diagnosed with hsp and suspected superior mesenteric vein thrombosis . we reviewed the relevant literature and found eight similar reported cases . hsp is associated with thrombosis and hsp itself and some risk factors may result in thrombosis . we suggest that physicians should monitor patients with hsp who are at a higher risk of developing thrombosis more closely .

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it is characterized by acute and mostly intense abdominal pain accompanied by peritonism and potentially meteorism , nausea , vomiting and in severe and advanced cases shock . in most cases abdominal pathologies cause this acute condition including but not limited to appendicitis , cholecystitis , pancreatitis , mesenteric ischemia , ileus and perforations of hollow organs , . however , also extra - abdominal diseases can present with symptoms of an acute abdomen such as testicular torsion , myocardial infarction or diabetic ketoacidosis . due to the fact that an acute abdomen is always potentially life - threatening , prompt action is required to obtain the diagnosis and to immediately initiate adequate therapy . diagnostically , in addition to clinical examination and analysis of serum parameters , imaging such as sonography , computed tomography ( ct ) and magnetic resonance imaging ( mri ) are foremost in leading to the correct diagnosis . however , as mentioned above , the causes for acute abdominal symptoms are versatile and at times are found in medical areas other than gastroenterology itself . in this study we report on an interesting and unique case in which a psychiatric condition was the underlying disease leading to an acute abdominal picture which required immediate surgical intervention . a 28-year - old woman presented in our surgical emergency unit with a sudden onset of progressive abdominal discomfort and pain . routine laboratory analysis did not show any pathologies , including normal hemoglobin , leucocytes , c - reactive protein ( crp ) as well as serum electrolytes . because of the acute and dramatic clinical presentation we immediately performed a computed tomography of the abdomen . this revealed a massively distended stomach with a cranio - caudal extension of 35 cm reaching the lesser pelvis , however , without evidence for perforation ( figure 1 ( fig . a stomach tube was placed , which , however , did not drain any significant amount of stomach content . we performed a gastrotomy of the gastric antrum and recovered ( over the period of one hour ) a large amount of cementitiously clotted and undigested food scraps from the stomach . the stomach tube as well as the intrabdominal drainage could be removed within the first days after surgery . a gradual reintroduction of liquids was well tolerated . on the sixth postoperative day we performed a radiological imaging of the stomach using contrast medium which revealed a re - tonised stomach of a normal size without evidence for any stenosis ( figure 2 ( fig . subsequently , the patient was allowed to normal food intake , which was well tolerated as well . the postoperatively initiated evaluation of the patient by a psychiatrist revealed that she had been suffering from an eating disorder since her childhood . temporarily , her body mass index ( bmi ) had dropped to 11 kg / m . at consultation in our clinic however , the patient reported on daily binge eatings caused by conflicts at her workplace . this had also occurred on the day of hospital admission , however on this day , the routinely self - induced vomiting after the binge attack failed . in a good status of health here , we report on an unusual case in which a binge attack in a young woman suffering from an eating disorder caused a massive dilatation of her stomach . this dilation was not reversible either by self - induced vomiting or by drainage using a stomach tube . some other authors have reported on cases in which eating disorders such as anorexia nervosa or bulimia nervosa lead to acute gastric dilatation , , , . in line with the higher incidence of eating disorder in young females , mostly women in the age between 14 and 30 years were affected . in some cases , the so - called superior mesenteric artery syndrome has been suggested to cause or at least promote gastric dilatation in patients with eating disorders , . for this syndrome it has been proposed that malnutrition leads to the shrinkage of a fad pad localized between the aorta and outlet of the superior mesenteric artery . this , in turn , may cause compression of the duodenum thereby promoting gastric dilatation , in particular in cases when eating binges occur . in the reported case of this study , immediate imaging revealed the diagnosis and emergency explorative laparotomy and gastrotomy allowed for full recovery of the patient without complications or any residuals . this prompt and direct action including emergency laparotomy appears to be justified and essential , given the fact that some authors have reported severe complications such as gastric perforation and/or necrosis in patients with similar conditions , . furthermore , in some cases extended surgical approaches such as partial gastrectomy or even gastric resection were required . the fact that some patients did not recover and , unfortunately , passed away , confirms the severity of this condition as well as the importance of adequate diagnosis and immediate ( surgical ) therapy .

the clinical picture of an acute abdomen is frequently encountered in emergency medicine . in most cases abdominal pathologies underlie this condition , however , also extra - abdominal diseases may present or cause an acute abdomen . the fact that this condition is potentially life - threatening highlights the importance of instant action . here , we report on the case of a young woman that presented with an acute abdomen in our clinic . imaging revealed a massively distended stomach reaching the lesser pelvis . initially , the etiology for the gastric dilatation remained unsolved . on the same day we performed an explorative laparotomy in which massive amounts of clotted , undigested food was recovered via a gastrotomy . postoperatively , upon psychiatric consultation , an eating disorder with daily eating binges could be revealed as being the cause for the acute and dramatic gastric dilatation . the patient fully recovered from surgery and psychiatric co - treatment was initiated . this unique case report demonstrates how a psychiatric condition may lead to an acute abdomen , however , it also emphasizes the importance of prompt diagnosis and adequate therapy to avoid complications and allowing for full recovery .

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jadb : assigned ( as a medical student ) to patient during hospitalization and participated in review of the literature , drafting , and editing of case report . jan : attending assigned to patient during hospitalization and performed editing of case report and final approval . sjs : provided nephrology consult during hospitalization and performed editing of case report and final approval .

key clinical messagesubcutaneous fat necrosis ( sfn ) in infants producing severe hypercalcemia is a lifethreatening emergency . pathophysiology may include enhanced gastrointestinal calcium absorption and bone resorption . we treated an infant with sfn and serum calcium of 15 mg / dl with prednisolone and lowdose zoledronic acid . serum calcium promptly normalized without rebound hypocalcemia , and redosing of zoledronic acid was not necessary .

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peritonitis is one of the most common factors responsible for morbidity and mortality in patients on continuous ambulatory peritoneal dialysis ( capd ) . approximately 48% of peritonitis episodes have a fungal etiology , candida species accounting for 75% . the reported incidence of mortality in bacterial peritonitis is approximately 0.63% and that in fungal peritonitis is 1244% . so , it is imperative that fungal peritonitis is diagnosed rapidly and appropriate treatment given so that the survival rates are improved . paecilomyces species are saprophytic fungi and are uncommon pathogens that can produce serious infections in immunocompromised patients and occasionally in immunocompetent hosts . reddy et al . reported a case of fungal peritonitis caused by paecilomyces puntonii from india . we report a case of fungal peritonitis caused by paecilomyces varioti , which is not reported from india till date to the best of our knowledge . a 51-year - old man was on capd had 2 episodes of culture negatibe peritonitis over the period of 2 years . first episode 2 months after the initiation of capd was treated with empirical antibiotics ( vancomycin and amikacin ) by intraperitoneal route ; second episode 6 months prior to current admission and was treated with the same antibiotics . he again presented with complaints of diffuse abdominal pain and high grade fever with cloudy pd effluent . his pd effluent cell count was 3000 cells / mm with 80% polymorphs , gram stain and afb stain were negative , aerobic cultures did not grow any organism . fungal cultures by sabouraud dextrose agar medium had grown filamentous fungi after 48 hours and microscopically it showed chains of single celled phialoconidia produced in basipetal succession from a phialide . phialides are swollen at their bases , gradually tapering towards their apices and formed a brush - like penicillus confirming the diagnosis of p. varioti [ figure 1 ] . accordingly capd catheter was removed , he was initiated on hemodialysis mode amphotericin b was started at 1 mg / kg / day . he was treated for a period of 4 weeks with a cumulative dose of 1.5 g of amphotericin . capd catheter reinsertion was done successfully , he is currently on pd and is doing well . microscopic morphology of paecilomyces varioti showing chains of single celled phialoconidia produced in basipetal succession from a phialide . phialides are swollen at their bases , gradually tapering towards their apices and may form a brush - like penicillus in recent years , unusual and nonpathogenic fungi like paecilomyces have been increasingly reported as etiologic agents of fungal peritonitis . paecilomyces are common saprophytic fungi found in soil , silage , and water . they are not usually associated with human infection . however , some species such as p. varioti , p. marquandii and p. lilacinus are emerging as causative agents of hyalohyphomycosis in the immunocompromised host . p. varioti have been reported to cause pyelonephritis , endophthalmitis , hairy - cell leukemia , cerebrospinal shunt infection , and prosthetic valve endocarditis . the most important risk factors for fungal peritonitis are prolonged use of antibiotics and previous bacterial peritonitis episodes . a study by goldie et al . reported that 65% of fungal peritonitis patients had received broad - spectrum antibiotics within the preceding month , 74% within 3 months , and 87% within 6 months . our patient presented with fungal peritonitis 6 months after empirical antibiotic therapy for suspected bacterial peritonitis . several case series reported increased dialysate eosinophils . in other reported cases as well as in our patient , no eosinophilia was found in the dialysate . the conventional antifungal regimens include fluconazole , amphotericin b , and flucytosine alone or in combination , based on fungal sensitivities . p. varioti is usually very sensitive to amphotericin b. we used intravenous amphotericin b for our patient who responded dramatically with cumulative dose of 1.5 g. it can be easily treated with common antifungal agents like amphotericin b which can facilitate catheter reinsertion .

peritonitis is one of the most common and important complications in patients on continuous ambulatory peritoneal dialysis ( capd ) . fungal peritonitis isreported in 48% of peritonitis episodes . fungal peritonitis due to paecilomyces species is not common . we report a case of capd peritonitis due to p. varioti . we immediately removed the capd catheter and iv amphotericin was administered for 4 weeks along with temporary hemodialytic support followed by successful catheter reinsertion .

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intravenous thrombolytic therapy when given within 4.5 h from symptom onset remains the mainstay of treatment for ischemic stroke patients . while intravenous tissue plasminogen activator ( iv tpa ) has been shown to be effective in improving outcome , the most feared complication is symptomatic intracerebral hemorrhage ( sich ) , which occurs in up to 7 percent of patients and significantly increases mortality and morbidity . standard management of post thrombolysis intracerebral hemorrhage includes replacement of coagulation factors with cryoprecipitate and platelets , as suggested by the american heart association , which is based on small case series and expert opinion and the efficacy of such treatment is unknown . thus there exists heterogeneity in clinical practice with respect to the strategies implemented in the management of sich . the lack of consensus on how to manage sich as well as continued poor outcomes despite treatment should create a driving force in the stroke community to investigate effectiveness and rapidity of other potential treatment options . we report a 68-year old right handed hispanic woman with a history of diabetes mellitus type ii , hypertension , hyperlipidemia , and two prior strokes with residual right hemiparesis , who presented with sudden onset vertigo , slurred speech , and blurred vision . the first stroke was a left putamen intracerebral hemorrhage with minimal residual right hemiparesis that occurred over 20 years prior to admission . the second stroke was a cryptogenic stroke that occurred around 5 years prior to admission for which she was outside the time window of thrombolytic therapy and was maintained on aspirin 81 mg daily . her initial exam showed dysarthria , left sided sensory loss , skew deviation with upgaze vertical nystagmus , mild right hemiparesis , and an nihss score of 4 . initial head computed tomography ( ct ) ( figure 1a ) showed evidence of prior strokes and no acute hemorrhage . since she had a new fixed and potentially disabling neurological deficit and she was within the 4.5 h window , decision was made to administer thrombolytic therapy . an hour after the iv tpa infusion was complete , she complained of an acute severe headache without a change in neurological exam and repeat ct head showed right temporal ich with a subdural component ( figure 1b ) . two hours after the completion of this treatment , she became somnolent and had new left hemiparesis . ct head was repeated that showed ich expansion and new intraventricular hemorrhage ( figure 1c ) . in the next 3 h head ct at that point showed further expansion of ich and intraventricular hemorrhage ( figure 1d ) . the decision was made to administer recombinant factor viia ( 50 mcg / kg ) and she was subsequently taken to the operating room with successful clot evacuation . postoperatively , her exam slowly improved and she was back to her baseline neurological exam on post - operative day 3 ( figure 1e ) . alteplase converts plasminogen to plasmin , which in turn converts fibrin into the fibrin split products causing thrombolysis . it also causes a reduction in fibrinogen the degree of which is associated with sich . using cryoprecipitate ( factor viii and fibrinogen ) , in post thrombolysis sich increases fibrinogen levels , enhances fibrin formation and may potentially stabilize the clot thus reducing the risk of further hemorrhage . however , a study from get with the guidelines data showed that around 40 percent of patients with post thrombolysis sich have continued bleeding despite cryoprecipitate treatment . the lack of efficacy may be due to delays in diagnosis and treatment , insufficient dosing of cryoprecipitate to replenish fibrinogen , or lack of augmentation with rapid acting factors that help convert fibrinogen into fibrin . to our knowledge , this is the first case reporting the use of recombinant factor viia along with cryoprecipitate and platelets in the treatment of symptomatic ich following intravenous thrombolysis . activated factor viia has been studied in spontaneous intracerebral hemorrhage and has been shown to reduce hematoma growth with no effect on mortality and morbidity however . activated factor viia , which has a relatively quick time of onset and is an extrinsic and intrinsic pathway activator , may further enhance clot stability and potentially reduce the risk of hematoma expansion , which is likely what happened with our patient . although recombinant factor viia carries a risk of thrombosis and is relatively expensive , its use in this patient population may potentially alter the course of the disease and improve outcome . randomized studies may be considered to compare the outcome of patients with post thrombolysis sich when rapid reversal agents such as recombinant factor viia or prothrombin complex concentrate are added to the standard treatment or given in isolation .

symptomatic intracerebral hemorrhage ( sich ) occurs in up to 7% of stroke patients treated with thrombolytic therapy . there are limited data on the effectiveness of the reversal agents used for intravenous tissue plasminogen activator related intracranial bleeds . we report a patient with sich following intravenous thrombolysis whose intracerebral hemorrhage continued to expand despite treatment with platelets and cryoprecipitate , needing recombinant factor viia use for stabilization before surgical evacuation . factor viia along with routine reversal agents following intravenous thrombolysis related sich may further enhance clot stability and reduce the risk of hematoma expansion . it could be a bridge to definitive surgical management in those patients .

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glandular odontogenic cyst ( goc ) is a rare lesion that arises in the tooth bearing areas of the jaws . padayachee and van wyk initially reported it as a sialodontogenic cyst in 1987 based on the possibility of salivary gland origin but its odontogenic origin was first described in 1988 by gardner et al . , who proposed the name goc because the cyst wall epithelium was odontogenic and contained mucin elements with no evidence of salivary tissue involvement . the term mucoepidermoid cyst or mucous producing cyst was used by sadeghib in 1991 due to the microscopic findings of mucus producing cells and squamous cells . in the 1992 world health organization ( who ) typing of odontogenic tumors , goc was defined as a cyst arising in the tooth - bearing areas of the jaws characterized by an epithelial lining with cuboidal or columnar cells both at the surface and lining crypts or cyst - like spaces within the thickness of the epithelium . goc is relatively rare lesion with a frequency rate of 0.012 - 1.3% of all the jaw cysts and its prevalence rate is 0.17% . it has two clinically important attributes : a high recurrence rate and an aggressive growth potential . goc primarily occurs in middle - aged patients with slight male predilection and the most common site of occurrence is mandibular anterior region where it usually presents as a painless , slow - growing swelling . radiographically , these cysts are described as well - defined , unilocular or multilocular without specific diagnostic characteristics . histologically , goc shows a non - keratinized stratified squamous epithelial lining , focal plaque like thickenings within the lining , microcysts or intraepithelial crypts containing mucin , mucous cells and hyaline bodies , eosinophilic cuboidal or columnar cells that may be ciliated , papillary projections of epithelium and absence of inflammation in the subepithelial connective tissue . the relative rarity of the lesion prompted us to add one more of our case and review the literature . a 30-year - old female patient reported with a swelling in the upper right back region of the jaw . the swelling was present since 8 months which was painless and increased gradually in size . intraorally a diffuse , non fluctuant and firm swelling was seen with normal overlying mucosa extending from the buccal aspect of 11 - 17 obliterating the vestibule [ figure 1 ] . panoramic radiographic examination revealed a well - defined unilocular radiolucency extending from 15 - 17 . 16 was carious with root resorption and roots of 15 and 17 were displaced [ figure 2 ] . gross examination showed a smooth to rough mass measuring 2.5 2 cm and the cut section showed a cystic wall filled with necrotic material [ figure 3 ] . histopathologic examination , revealed a cystic cavity lined by a non keratinized stratified squamous epithelium with surface layer composed of ciliated columnar cells [ figures 4 and 5 ] . immunohistochemistry ( ihc ) staining was done using ck-18 , ck-19 , p53 , ki-67 . among them clinical photograph shows swelling in the upper right back region of the jaw orthopantomogram shows radiolucent area in 15 , 16 , 17 region gross specimen showing a smooth lobulated mass photomicrograph shows lining epithelium ( h&e stain , 100 ) photomicrograph shows surface ciliated columnar epithelium ( h&e stain , 400 ) photomicrograph shows special stained mucous cells ( pas stain , 400 ) photomicrograph shows strong positive immunoreactions to the ki-67 protein ( ihc stain , 100 ) photomicrograph shows strong positive immunoreactions to the ck-19 protein ( ihc stain , 100 ) goc is a relatively rare entity . magnusson and co - authors evaluated 5900 cases of jaw bone cysts and found only 7 cases of goc , about 0.12% ; whereas van heerden and others reported 1.3% of goc in their study . in the present case the patient is a middle - aged female whereas existing literature reports a slight male predilection . the most common site of occurrence is the anterior region of mandible followed by anterior region of maxilla and posterior region of mandible . about three cases have been reported till date and ours is probably the fourth case . a diagnosis based only on clinical and radiological examination is difficult because of similarities with various other intrabony pathologies , hence a histopathological evaluation becomes mandatory . the histopathological characteristics of goc have been divided into major and minor categories by kaplan et al . goc should be distinguished from lateral periodontal cyst , botryoid odontogenic cyst , surgical ciliated cyst , radicular cyst with mucous metaplasia and central mec as it exhibits considerable overlapping of histopathological features [ figure 9 ] . , in their study found that goc showed positivity for p53 and ki-67 . when compared to mec , these markers could be auxillary aids in the differential diagnosis of these lesions . according to various authors , positive immunostaining with ck-18 and ck-19 in goc may further help in differentiating goc from central mucoepidermoid carcinoma ( mec ) . a recent study found significantly higher expression of both cytoplasmic and nuclear maspin in the mucous cells in low grade mec ( 16.5% cytoplasmic , 1.7% nuclear ) as compared with goc ( 1.5% and 0.3% ) or odontogenic cysts with mucous metaplasia ( 1% and 0.4% ) . several treatment modalities have been used which include curettage , enucleation with careful dissection of the margins and local block excision . however , the aggressive nature of the lesion has been reported and the recurrence rate is directly related to the size of the lesion . therefore , large lesions should be treated more aggressively and followed for a long period . it is important to consider histopathological features for its diagnosis since it bears resemblance to lesions like mec .

glandular odontogenic cyst ( goc ) is an uncommon jaw bone cyst of odontogenic origin described in 1987 by gardner et al . it is a cyst having an unpredictable and potentially aggressive behavior . the increased recurrence rate can be due to its multilocularity and incomplete removal of the lining following conservative treatment . clinically , the most common site of occurrence is the anterior region of mandible . goc has a slight male predilection and occurs primarily in middle - aged patients . this article presents a case of glandular odontogenic cyst in a 30-year - old female patient in the posterior region of the maxilla , which is quite rare .

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in recent studies , drug - eluting stents ( des ) were more widely used than bare - metal stents ( bms ) in patients who underwent percutaneous coronary intervention ( pci).1 recently , several significant complications after implantation of des have been reported , and stent thrombosis ( st ) is a rare but fatal complication among them . discontinuation of dual antiplatelet therapy is known to be a risk factor for st in patients after implantation of des.2 - 4 therefore , dual antiplatelet therapy is recommended to be maintained for at least 12 months after stent implantation to prevent late stent thrombosis ( lst ) or very late stent thrombosis ( vlst ) . however , it is still unclear how long dual antiplatelet therapy is needed and when the antiplatelet therapy can be safely stopped . here we report a case of a patient with acute myocardial infarction due to vlst that occurred 1 week after discontinuation of 5 years of dual antiplatelet therapy after implantation of a sirolimus - eluting stent . a man with no risk factors for coronary artery disease except smoking underwent pci in may 2005 at age 44 . a 3.023 mm cypher stent was deployed in the proximal right coronary artery . seven days after the discontinuation of clopidogrel , he experienced severe chest pain and was transported to the emergency room by ambulance . a physical examination revealed a temperature of 36.0 , blood pressure of 90/60 mmhg , and a regular heart rate of 100 beats / min without murmur or gallop . pulmonary rales , peripheral edema , or other clinical signs of congestive heart failure were not present . an electrocardiogram revealed st - segment elevation in lead ii , iii , and avf . the peak level of creatine kinase ( ck ) was 1,334 u / l , ck - mb was 75.4 u / l , and troponin - i was 38.1 ng / ml . transthoracic echocardiography in the emergency room revealed inferior wall akinesia , and his ejection fraction was 45% . the patient received 300 mg of aspirin and 600 mg of clopidogrel as a loading dose and was transferred to the cardiac catheterization laboratory . his pain to door time was about 60 minutes , and the door to balloon time was 72 minutes . an emergent coronary angiogram revealed a thrombotic total occlusion at the proximal right coronary artery ( fig . the occluded right coronary artery was revascularized successfully by balloon angioplasty with a 3.020 mm balloon ( fig . after pci , ultegra rapid platelet function assay ( rpfa)-asa and ultegra rpfa - p2y12 ( verifynowassay ) were performed to determine aspirin and clopidogrel resistance . the patient was discharged uneventfully and followed up with dual antiplatelet therapy of aspirin and clopidogrel . there have been no adverse events with clinical follow - up for 1 year , and a follow - up coronary angiogram revealed no significant stent restenosis . des interrupt re - endothelialization of the vessels , which results in a lower rate of target lesion revascularization than with bms . long and multiple stents , stent under - expansion or stent malposition , residual dissection , and resistance to aspirin and clopidogrel have been suggested as other possible causes of st.5 - 7 several studies revealed a higher rate of lst and vlst after des implantation than after bms implantation . dual antiplatelet therapy reduces subacute thrombotic events after pci , and at least 12 months of dual antiplatelet therapy after pci is recommended in the current guidelines to prevent st . whether long - term maintenance of dual antiplatelet therapy can prevent lst or vlst is still controversial . park et al reported that clopidogrel continuation beyond 1 year did not appear to decrease stent thrombosis and clinical events after des implantation,8 although tanzili et al concluded that 2 years of dual antiplatelet therapy can prevent the occurrence of vlst after des implantation.9 triple antiplatelet therapy adding cilostazol is considered to be another choice for preventing stent thrombosis in patients with clopidogrel resistance or for the prevention of recurrent stent thrombosis . the disadvantage of triple therapy is the bleeding tendency , but the bleeding tendency of triple therapy was reported to be not much higher than that of dual antiplatelet therapy in several studies . however , the effect of triple therapy on long - term survival or cardiac events is controversial as well.10,11 in this patient , there were no risk factors for st except former smoking and no evidence of aspirin or clopidogrel resistance . the patient had been treated with dual antiplatelet agents for enough time ( 5 years ) after des implantation , but vlst occurred at 1 week after discontinuation of clopidogrel . we concluded that 12 months of dual antiplatelet therapy may not be enough for the prevention of lst or vlst after des implantation in some patients who do not show complete re - endothelialization of the coronary artery . concerning the decision to cease clopidogrel therapy , we suggest that it should depend on the condition of the patient and risk factors for st such as underlying disease , the length or location of the lesion , the resistance of aspirin or clopidogrel , and so on . perhaps the development of imaging systems such as optical coherence tomography will give us more precise information . we suggest that physicians educate their patients about the hazards of premature cessation of dual antiplatelet therapy and delay performing surgical procedures until 1 year after implantation of des .

drug - eluting stents ( des ) have reduced the rate of repeated revascularization of target lesions . for this reason , des are considered to be superior to bare - metal stents in reducing the restenosis rate . however , some problems have been reported after implantation of des . one of them , stent thrombosis , has arisen as a fatal complication . dual antiplatelet therapy is recommended for at least 12 months after implantation of des to prevent stent thrombosis . here , we report a case of very late stent thrombosis that occurred 1 week after discontinuation of clopidogrel at 5 years ( 1832 days ) after implantation of a sirolimus - eluting stent .

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the interpretation of a raised amylase in the acute surgical patient is crucial yet complicated as it is raised in a large number of conditions but with a low specificity . this report argues that a transient rise in serum amylase not caused by sepsis or pancreatitis can be caused by a splenic infarction . therefore any cause of a non - diagnostic amylase rise must not be over- looked as it may be of diagnostic value in a life threatening surgical condition . a 49-year - old previously well male , presented with a 24 hour history of vomiting , abdominal pain and fever . his abdominal pain was of rapid onset and localised to the epigastrium and left upper quadrant . there was no history of trauma but he did admit to a recent history of alcohol excess . clinical examination revealed diffuse upper abdominal tenderness , a mild tachycardia and a low grade pyrexia . blood work up revealed an amylase of 270 u / l and crp of 125mg / l . ct showing evidence of splenic infarction secondary to infective endocarditis a provisional diagnosis of alcohol - induced pancreatitis was made . he received standard management as mild pancreatitis ( glasgow score 0 ) with ward level care . an ultrasound showed no abnormality . due to diagnostic uncertainty and failure of symptoms and signs to rapidly resolve , subsequent echocardiogram for a source of emboli showed multiple valvular vegetations , aortic regurgitation and a 16 mm pericardial effusion . treatment with intravenous flucloxacillin and gentamicin was undertaken and transfer to the regional cardio - thoracic unit was arranged . there he underwent urgent aortic valve replacement with a tissue valve following which he made an uncomplicated recovery . these can be broadly grouped into 3 subdivisions : pancreatic ( eg . pancreatitis , pancreatic tumour or trauma)extra - pancreatic intra - abdominal disease ( eg . cholecystitis , perforated duodenal ulcer , bowel ischaemia)extra - abdominal processes ( eg . macro - amylasaemia ) pancreatic ( eg . pancreatitis , pancreatic tumour or trauma ) extra - pancreatic intra - abdominal disease ( eg . cholecystitis , perforated duodenal ulcer , bowel ischaemia ) extra - abdominal processes ( eg . macro - amylasaemia ) interpretation of a raised amylase in the surgical patient is crucial , potentially avoiding dangerous misdiagnosis . many conditions cause hyperamylasaemia making the specificity of elevated serum amylase level less than 70% . its low specificity drops further after the first 24 hours of hospital admission ( 1,2 ) . elevated serum amylase activity in pancreatitis is attributed to pancreatic auto - digestion , but its pathophysiology is unknown in many other causes . endocarditis is a well known cause of splenic thrombosis and consequent infarction and first described in germany in 1869 ( 3 ) . there have been reports of raised amylase in non - pancreatic sepsis , some showing that this could be used as a prognostic marker in the septic patient ( 4 ) . however , in this patient the transient amylase rise dropped despite worsening sepsis , suggesting an alternative cause for the disturbance . recent studies by antopolsky et al examined clinical presentations in 49 episodes of acute splenic infarction . the most common symptom was abdominal or left flank pain ( 80% of episodes ) with the most common sign being upper left quadrant tenderness ( 35% of episodes ) ( 5 ) . clinicians should be aware of splenic infarction as a clinical entity , and consider it in cases of upper abdominal pain , particularly if there is a non - diagnostic amylase rise .

we present what maybe the only case of splenic infarction causing hyperamylasaemia in a patient with bacterial endocarditis . a 49-year - old gentleman presented a 24 hour history of vomiting , abdominal pain and fever . clinical examination showed diffuse upper abdominal tenderness , a mild tachycardia and a low grade pyrexia . blood investigations showed a hyperamylasaemia . his failure to improve on treatment for a provisional diagnosis of alcohol induced pancreatitis lead to a ct abdomen , which showed a splenic infarct and an echo showing aortic valve vegetation 's as a source of emboli . he underwent urgent aortic valve replacement with a tissue valve following which he made an uncomplicated recovery .

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nanoporous silica particles were synthesized and characterized as described previously and as detailed in supplementary figure 1 and the supplementary methods section . particles larger than 150-nm in diameter were removed via differential centrifugation or size - exclusion chromatography ( see supplementary figs . 1a and 1d ) . protocells were formed by fusing 120-nm liposomes to the nanoporous core as reported previously , and the composition of the slb was optimized to reduce non - specific binding associated with cationic and , to a lesser extent , anionic lipids ( see supplementary fig . 5 ) . zwitterionic lipids ( dopc or dppc ) with 5 wt% phosphatidylethanolamine ( dope or dppe , respectively ) , 5 wt% peg-2000 pe ( 18:0 or 16:0 , respectively ) , and 30 wt% cholesterol were used in all further studies ; pegylated lipids were incorporated into the liposomes used for fusion and are , therefore , expected to be present on both the inner and outer leaflets of the slb . the size of the nanoporous core was also optimized to attain a balance between achievable cargo capacity and the rate of protocell internalization ( see supplementary fig . 9 ) ; nanoparticles 100- to 150-nm in diameter were employed in the delivery of drugs , drug cocktails , sirna cocktails , and protein toxins . the nanoporous cores were soaked in a 10 mm solution of cargo(s ) for 1 - 12 hours prior to liposome fusion ; individual components of the surrogate cargo mixture ( fig . the rates of cargo release were optimized by incorporating various percentages of aeptms , an amine - containing silane , into the sol used to form nanoporous cores ( see supplementary fig . particles containing 15 wt% aeptms were used to deliver drugs and drug cocktails ( fig . 6 ) , while particles containing 20 wt% aeptms were used to deliver the multicomponent mixture ( fig . 5 ) , the sirna cocktail ( supplementary figs . 13 and 14 ) , and diphtheria toxin a - chain ( supplementary figs . 15 and 16 ) .

encapsulation of drugs within nanocarriers that selectively target malignant cells promises to mitigate side effects of conventional chemotherapy and to enable delivery of the unique drug combinations needed for personalized medicine . to realize this potential , however , targeted nanocarriers must simultaneously overcome multiple challenges , including specificity , stability , and a high capacity for disparate cargos . here we report porous nanoparticle - supported lipid bilayers ( protocells ) that synergistically combine properties of liposomes and nanoporous particles . protocells modified with a targeting peptide that binds to human hepatocellular carcinoma ( hcc ) exhibit a 10,000-fold greater affinity for hcc than for hepatocytes , endothelial cells , and immune cells . furthermore , protocells can be loaded with combinations of therapeutic ( drugs , sirna , and toxins ) and diagnostic ( quantum dots ) agents and modified to promote endosomal escape and nuclear accumulation of selected cargos . the enormous capacity of the high - surface - area nanoporous core combined with the enhanced targeting efficacy enabled by the fluid supported lipid bilayer allow a single protocell loaded with a drug cocktail to kill a drug - resistant hcc cell , representing a 106-fold improvement over comparable liposomes .

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the utah lions eye bank has harvested 159 eyes from strangulations or hangings since 2003 . of these , 18 eyes ( 11% ) were not suitable for surgery , with 13 eyes being excluded during the screening process . the reasons for exclusion included hepatitis b positivity , human t lymphotrophic virus positivity , high risk of creutzfeldt - jakob disease , low endothelial cell count , or time spent incarcerated . the final two eyes belonged to a 25-year - old male who was found hanging and unresponsive . his past medical history was significant for depression , previous suicide attempts , peritonitis , and an appendectomy , with an unremarkable past ocular history . following dissection of the corneoscleral buttons by the utah lions eye bank , total detachment of descemet s membrane was seen in both corneas ( figure 1 ) . the corneas were deemed unsuitable for transplant surgery , and the tissue was sent to another eye bank for use in keratolimbal allografts . the donor s corneoscleral buttons were retrieved by a skilled tissue recovery specialist with many years of experience . iatrogenic trauma during tissue retrieval can not be ruled out since corneas of intact globes are not routinely examined prior to removal . however , this is unlikely to cause such dramatic findings of complete descemet s membrane detachments bilaterally . to our knowledge , this is the first reported case of extensive descemet s membrane detachment following a hanging . dyer observed the hanging of a prisoner and reported a post mortem fracture through the crystalline lens and anterior lens capsule in the prisoner s right eye . he reproduced these findings by hanging three dogs , with two of six eyes showing similar damage following death.1 in 1869 he saw five more hangings , and found crystalline lens and anterior capsule fractures in three of 10 eyes.2 we speculate that a dramatic rise in intraocular pressure during hanging may stretch the cornea and cause rupture of descemet s membrane . tears in descemet s membrane may occur in congenital glaucoma when the intraocular pressure increases , causing an elongation in axial length and subsequent stretching of the cornea.3 recent research has examined how forces applied to the head influence intraocular pressure . bakaran et al measured intraocular pressure in yoga practitioners during sirsasana ( the headstand posture ) and found mean intraocular pressure increased two - fold in patients immediately after assuming this position.4 aykan et al found that the intraocular pressure increases significantly during valsalva movements.5 hanging may cause increased intraocular pressure secondary to increased venous pressure in the brain . he et al examined brain lesions caused by hanging via magnetic resonance imaging and found a venous distribution of brain damage.6 we suggest that further research on the effect of increased venous pressure and iop on corneal tissue is needed . furthermore , we would be interested in learning if other eye banks have observed similar corneal tissue changes following strangulation or hanging .

the eyes of a 25-year - old male were collected by the utah lions eye bank after his suicide by hanging . following dissection of the corneoscleral buttons from intact globes , bilateral detached descemet s membranes with subsequent scrolling in the periphery were observed . we believe these findings were caused by a large increase in intraocular pressure secondary to the hanging . lens and anterior capsule fractures after hanging have been reported , but corneal damage has never been discussed . we invite transplant surgeons and eye bank recovery specialists to share their experience of similar corneal changes in donated eyes following strangulation or hanging .

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histoid leprosy is an uncommon variant of lepromatous leprosy characterized by cutaneous / subcutaneous nodules and plaques present over apparently normal skin , with unique histopathological findings , characteristic bacterial morphology and very high bacillary load . the term histoid leprosy was coined by wade as a histological concept of bacillary - rich leproma composed of spindle - shaped cells in the absence of globi ( so conspicuous in an ordinary leproma ) . it occurs in lepromatous patients who relapse after the dapsone monotherapy and resistance , or even de novo . responsible factors may include resistance to dapsone , irregular and inadequate therapy , or mutant organism ( histoid bacillus ) . he had no complains of fever , epistaxis or slippage of sandals . on examination , multiple shiny papulonodular lesions were found over his forehead , ears , and cheeks [ figure . bilateral ulnar , greater auricular , common peroneal , anterior tibial , and posterior tibial nerves were thickened . on histopathological examination , sections showed extensive cellular infiltration in the dermis mainly composed of macrophages , lymphocytes and plasma cells . hematoxylin and eosin stain showed histiocytes arranged in a storiform pattern with classical histiocytic granulomas [ figure . 2 ] and heavy bacillary load on wade fite stain . slit skin smear revealed acid fast bacilli with a bacteriological index of 6.[figure . 6 ] wade fite stain revealed numerous solid staining acid fast bacilli arranged discretely and in clumps inside the dermis , including the grenz zone , and surprisingly also inside the epidermis , inside vacuoles in the prickle cell layer and in the stratum granulosum.[figure . 35 ] the presence of bacilli at various levels inside the epidermis suggested their movement upward along with epidermal cell maturation . multiple shiny succulent papulonodular lesions over the forehead , cheeks , and chin histopathology showing extensive cellular infiltration in dermis mainly composed of macrophages , lymphocytes and plasma cells with histiocytes arranged in a storiform pattern with classical histiocytic granulomas wade fite stain revealed numerous acid fast bacilli arranged in clumps inside the epidermis wade fite stain revealed numerous solid staining elongated slender acid fast bacilli arranged discretely in vacuoles in the stratum corneum , prickle cell layer and in the stratum granulosum wade fite stain revealed numerous solid staining elongated slender acid fast bacilli arranged discretely and in clumps inside the epidermis and in in dermis slit skin smear showing numerous acid fast bacilli histoid leprosy presents with shiny , skin colored or erythematous papules , nodules or plaques arising abruptly over normal skin , mostly after inadequate or irregular treatment or because of dapsone resistant mutant strains , but may occur de novo . in a recent indian report , histoid leprosy was found to constitute 1.8% of all leprosy cases and occurred de novo in 12.5% of cases . there are scant reports of detection of mycobacterium leprae inside the leprous epidermis and they could be missed / underreported unless specifically looked for . suggested that dermal bacilli could be gradually transferred to the epidermal layers through phagocytic activity of young basal cells , and finally eliminated , possibly through the intact skin . transepidermal elimination of m. leprae in lepromatous leprosy and attributed it to rapidly growing dense granulomas in the upper dermis . the presence of bacilli in all layers of epidermis indicates that the bacilli that are taken up by the basal cells from the upper dermis can move upward inside the epidermal cells and are ultimately eliminated from the stratum corneum into the environment . the very large area of skin of about 1.62 m in an adult indian and the average turnover time of about 28 days seems to provide an opportune environment for bacillary multiplication and elimination , as even 1 g of lepromatous tissue is estimated to carry up to 7 billion bacilli . it is also known that the bacilli once eliminated could remain viable for several days or weeks . as shown in polymerase chain reaction studies , 60% of untreated mycobacterium patients had bacilli in the keratin layer , and 80% had m. leprae deoxyribonucleic acid in skin washings . interestingly , on the other hand , the reports of initial / single leprosy lesions developing at the site of tattooing , vaccination scar or trauma suggesting that the bacilli could gain entry through traumatized skin . the recent report of linearly distributed skin lesions suggesting pseudo - isomorphic phenomenon of koebner in a histoid leprosy patient points toward cutaneous inoculation of the bacillus . dendritic cells are antigen - presenting cells that phagocytose microorganisms and particles and are represented by langerhans cells in the epidermis . they have a role in the cutaneous response to leprosy , which may be a determinant of the course and clinical expression of the disease . future studies on their contribution , if any , to the carriage of and response to the epidermal bacilli might help unravel a few unexplored aspects of leprosy . the transepidermal exit of the m. leprae demonstrated in this case , along with previous reports mentioned above , indicate that skin could possibly be a portal for both exit and entry of the bacillus causing the occurrence of pseudo - isomorphic koebner phenomena and should be given due recognition for its contributory role in leprosy transmission . suggested that upper dermal lepra bacilli in multibacillary patients could be phagocytosed by basal cells and gradually move up through the epidermis to be finally eliminated , possibly also from intact skin .

histoid leprosy is a rare form of multibacillary leprosy with distinct clinical and histopathological features . it is a variant of lepromatous leprosy with a very high bacillary load . it appears in patients as relapse after dapsone monotherapy and resistance or rarely , de novo . although leprosy is slowly declining the exact mode of transmission is unclear . at least until recently , the most widely held belief was that the disease was transmitted by contact between cases of leprosy and healthy persons . transmission by the respiratory route is also gaining ground . there are other possibilities such as transmission through insects , which can not be completely ruled out . however , the present case report possibly suggests the role of skin as a portal of both exit and entry for the bacillus in histoid leprosy transmission . de novo form of histoid leprosy has numerous solid staining bacteria inside the epidermis . the reports show that these bacilli can be eliminated from the intact epidermis , which indicate an unusual role of the skin in the transmission of leprosy .

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coronary artery spontaneous dissection is a rare and uncommon cause of sudden cardiac death and acute coronary syndrome . we report a case of a 31-year - old male admitted to our hospital with an acute coronary syndrome . a dissection of the left main coronary artery was diagnosed with a multidetector computed tomography ( ct ) scan and it was decided to perform an emergency coronary artery bypass grafting . a 31-year - old male , airline pilot , with no clinical history or cardiovascular risk factors , was admitted to the emergency room with 12 h history of retrosternal chest pain radiating to the jaw and upper extremities , during a trans - atlantic flight , which did not improve with analgesia . because of persistent pain , he came to our hospital . upon arrival to the emergency room , his vital signs were stable and he had a normal physical examination but complained of precordial pain . the cardiac enzymes were elevated and the ekg detected s - t changes consistent with mi ( fig . 1 ) . a multidetector ct coronary angiography was performed showing left main trunk dissection with 50% stenosis ( fig . figure 2:multidetector coronary angio - tomography reveals dissection at the ostium of the left main coronary artery . multidetector coronary angio - tomography reveals dissection at the ostium of the left main coronary artery . the patient underwent emergent coronary revascularization with saphenous vein grafts to the first obtuse marginal and the left anterior descending artery ( lad ) . control ct coronary angiography was performed 2 months later revealing patent aorto - coronary grafts ( fig . figure 3:ct coronary angiography reconstruction showing patent grafts to the lad and obtuse marginal arteries . in 1931 harold pretty described the first case of spontaneous dissection of a right coronary artery during the autopsy of a woman who presented with precordial chest pain . this condition is a rare cause of ischemic heart disease and affects mainly young healthy women . in 1987 , 85 cases were reported in the literature , currently more than 300 cases have been published [ 2 , 3 ] . before the coronariography era , these cases were reported during autopsies of patients having sudden cardiac deaths and its incidence may have been under - estimated . with the advent of these studies , the incidence has been reported to range between 0.07 and 1.1% . dissection of the lad artery is most common in women , whereas in men it is the right coronary artery [ 2 , 4 ] . the left main coronary artery involvement , like in our case , is rare , occurring in up to 12% of the cases , but is the most severe injury and presents as mi . hemodynamic and hormonal factors determine morphological changes in the arterial wall , and these may contribute to spontaneous dissection of the coronary arteries , with a peak incidence during the second week after birth [ 3 , 4 ] . to date , the pathophysiology is unclear [ 24 ] . in a subgroup of patients it is not possible to identify a specific condition causing spontaneous coronary dissection and is therefore classified as idiopathic . in patients with connective tissue disorders such as marfan s and ehlers danlos syndromes , predisposing to the dissection arises from medial degeneration of the coronary arteries . certain vasculitis , including systemic lupus erythematosus and polyarteritis nodosa , has been associated with the occurrence of coronary artery dissection . other factors that can cause vascular spasm and coronary dissection include intense exercise , sneezing and prolonged cocaine abuse [ 2 , 3 ] . it should show the presence of a double radiopaque lumen separated by a radiolucent intimal flap or a slow clearance of contrast from the false lumen . an intimal tear is present in only a minority of cases and a medial hematoma may not be recognized on coronary angiography as the medial hemorrhage may cause luminal narrowing or occlusion by pushing the inner media against the opposing wall . several cases in the literature have shown that ct coronary angiography provides additional information over invasive coronary angiography , with an accurate demonstration of the intimal flap and extent of the intramural hematoma . this study constitutes an emerging noninvasive alternative for diagnosis and also the follow - up of coronary artery spontaneous dissection . there are no specific guidelines for the management of spontaneous dissections of the coronary arteries [ 3 , 5 ] . coronary artery bypass surgery is indicated in patients with multivessel dissection , failed angioplasty and dissection of the trunk of the left main coronary artery [ 35 ] . although spontaneous dissection of a coronary artery is an uncommon condition , treatment should be based on the clinical status and imaging studies , including conservative and surgical means depending on the clinical presentation , location and characteristics of the dissection , we elected to proceed with surgery based on the ct findings .

spontaneous dissection of the coronary arteries is a rare disease with a wide range of clinical presentations ranging from angina to myocardial infarction ( mi ) ; its pathophysiology has not yet been fully established . in this paper , we present the case of a 31-year - old male with an acute coronary syndrome . the initial results of the electrocardiogram and cardiac enzymes were consistent with mi . however , a coronary angio - tomography revealed a dissection of the left main coronary artery and the patient underwent emergent surgery with coronary artery bypass grafting . the treatment of spontaneous dissection of the coronary arteries depends on the anatomical location and the patient 's clinical presentation . coronary revascularization is associated with good results .

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subtilisin solutions were prepared by mixing and vortexing of 1.25 , 5 , 8 , 12.5 , 15 , 17.5 , 20 , and 25 l of subtilisin stock solution ( sigma aldrich , catalogue number p4860 ; lot 056k1213 ) per ml of 100 mm phosphate buffer ( ph = 8 , filtered with a 0.25 m anotop filter ) , which yielded enzyme solutions at concentrations of 0.05 , 0.2 , 0.3 , 0.5 , 0.6 , 0.7 , 0.8 , and 1 mg ml . these concentrations correspond to 1.5 , 6 , 9.6 , 15 , 18 , 24 , and 30 u ml , expressed in activity units used in our previous report . saxs measurements were carried out at beamline 7t - mpw - saxs at bessy ii synchrotron source in berlin , germany , using an x - ray energy of 9650 ev . enzyme solutions at various concentrations as well as pure buffer ( as background ) were injected in glass capillaries and placed in a capillary holder . the capillary holder was then mounted on the sample cell chamber , evacuated , and heated to 25 or 55 c . the individual samples were then exposed to the x - ray beam to record scattering intensity patterns by using a gas detector placed in the vacuum chamber . the integration and processing of the scattering data was carried out by using the software provided at the beamline . static and dynamic light scattering measurements were carried out using the 3ddls instrument ( ls instruments , fribourg , switzerland ) using vertically polarized he ne laser light ( 25 mw with a wavelength of 632.8 nm ) with an avalanche photodiode detector at angles between 15 and 135 at 55 c . the background scattering intensities ( from pure buffer ) were subtracted from the scattering intensities of the enzyme solutions . at each scattering angle , dynamic light scattering measurements were also performed by recording the intensity autocorrelation function g2( ) as a function of lag time . the autocorrelation functions were analyzed by means of the cumulant method in order to determine the initial decay rate and the corresponding average apparent diffusion coefficient dapp . the decay of the normalized autocorrelation function was modeled as g1( ) = ( g2( ) 1 ) = exp( ) , where = dappq is the initial decay rate , q = ( 4n/ ) sin(/2 ) is the scattering vector magnitude , n is the refractive index of the solvent , and is the wavelength of the laser . einstein equation , rh = kbt/6dapp , where kb is the boltzmann constant , t is the absolute temperature , and is the solvent viscosity at the given temperature . the scattering intensity patterns from static light and x - ray scattering experiments can be described as i(q ) kp(q)s(q ) , where k is an instrument- and sample - dependent constant , p(q ) is the form factor , which depends on the size and shape of the primary particles , and s(q ) is the structure factor giving information about the spatial arrangement of the primary particles at length scales larger than that of the primary particles ( radius of rp ) . please note that q = ( 4/ ) sin(/2 ) for saxs measurements . in the limit of qrg < 1 , the mean radius of gyration rg of randomly distributed ( e.g. , freely diffusing ) primary particles or clusters can be determined from the measured scattered intensity i(q ) by using the guinier analysis . in the limit of 1/rg q 1/rp , where rg is the mean radius of gyration of a sufficiently large cluster composed of primary particles with radius rp , the structure factor for fractal clusters with fractal dimension df scales with q through a power law relation as i(q ) s(q ) q.

the structural characterization of subtilisin mesoscale clusters , which were previously shown to induce supramolecular order in biocatalytic self - assembly of fmoc dipeptides , was carried out by synchrotron small - angle x - ray , dynamic , and static light scattering measurements . subtilisin molecules self - assemble to form supramolecular structures in phosphate buffer solutions . structural arrangement of subtilisin clusters at 55 c was found to vary systematically with increasing enzyme concentration . static light scattering measurements showed the cluster structure to be consistent with a fractal - like arrangement , with fractal dimension varying from 1.8 to 2.6 with increasing concentration for low to moderate enzyme concentrations . this was followed by a structural transition around the enzyme concentration of 0.5 mg ml1 to more compact structures with significantly slower relaxation dynamics , as evidenced by dynamic light scattering measurements . these concentration - dependent supramolecular enzyme clusters provide tunable templates for biocatalytic self - assembly .

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non - traumatic convexal subarachnoid hemorrhage ( csah ) observed at the convexity of the brain is a relatively uncommon entity with various vascular and nonvascular causes . : cerebral venous thrombosis ( cvt),1 ) reversible cerebral vasoconstriction syndrome ( rcvs),4 ) vascular malformations , vasculitides,12 ) infectious aneurysms,10 ) moyamoya disease or syndrome,22 ) severe carotid atherosclerosis,6 ) posterior reversible encephalopathy syndrome ( pres),24 ) cerebral amyloid angiopathy ( caa),5 ) and nonvascular disorders , such as primary and secondary brain neoplasms7 ) or abscess.18 ) cerebral infarcts in the territory of the anterior cerebral artery ( aca ) are reported to comprise 0.5 - 3% of all ischemic strokes9)11 ) and few studies have specifically assessed the clinical characteristics of stroke patients with aca infarction.2 ) we report a case of aca cerebral infarction with spontaneous csah lead to stenosis of the aca . it is a infrequent case , but is worth consideration that the management and evaluation of these patients . a 59-year - old female patient visited emergency room with right side subjective weakness spontaneously . however , the national institute of health stroke scale ( nihss ) was 0 . initial computed tomography angiography at one and half hours after symptom onset demonstrated subarachnoid hemorrhage ( sah ) localized in the left frontal convexity and mild focal stenosis at both a2 segments . also the magnetic resonance diffusion - weighted images ( dwi ) revealed an acute infarction of anterior cerebral arterial territory ( fig . 1 ) . we could not find any vascular lesion on computed tomographic angiography ( cta ) and magnetic resonance angiography ( mra ) and treated with dual antiplatelet drugs ( cilostazole [ otsuka pharmaceutical co. , ltd . tokyo , japan ] 50 mg bid / day plus aspirin [ bayer pharma ag . , she has done well for a follow - up period and her modified rankin scale was 0 at day 5 . the follow - up evaluation was performed at out - patient clinic after 5 months . cta shows that the sah was washed out and encephalomalatic change in left aca territory . mri also reveals that no evidences of acute infarction in dwi and hemorrhagic transformation in susceptibility weighted imaging ( swi ) ( fig . although the prevalence of non - traumatic convexal sah is reported to be 7.5% of all spontaneous sah patients,13 ) little has been conscious of concerning the incidence of csah accompanying with acute infarction among many different etiologies of csah . demostrated the image protocol to cover the wide spectum of entities potentially responsible for csah that brain cta with a paired channel at both arterial and venous phases and mr imaging including gre t2 sequences , flair , dwi , mra 3d tof , contrast - enhanced venogram , and pre- and postgadoliniumt1-weighted imaging.3 ) however , we evaluated the cta and mr imaging cluding t2 , dwi , swi and 3d tof mra . cta and mra are useful to determine the vascular causes of csah such as vascular malformations , rcvs , vasulitides , high - grade stenosis , moyamoya disease , and septic aneurysms . in addition , mr imging is ascertainable diagnositic tools between dural and cortical cvt , and non - vascular causes such as , caa , pres , neoplasm , abscess and cavernoma . in this case , aca territory infarction seemed to occur hemodynamically because of stenotic lesion on a2 segment and hypoperfusion on brain spect with tc-99 m hmpao . nakajima et al . assumed that the accompanying an infarction and non traumatic csah might demonstrate that hemodynamic insufficiency because of arterial stenosis or occlusion get to the critical point . for instance , after an acute infarction due to occlusive disease by the embolic or hemodynamic mechanism , ensuing dynamic changes of intracranial perfusion pressure might bring about the csah.14 ) also cuvinciuc et al . explained that the main mechanism of csah because of chronic arterial occlusive diseases is considered to be the rupture of dilated vulnerable compensatory pial vessels.3 ) a large randominzed controlled trial studied clopidogrel and aspirin in high - risk patients with acute nondisabling cerebrovascular events ( chance ) was finished in china . the result revealed that antiplatelet double therapy with clopidogrel plus aspirin was better than aspirin alone for reducing the risk of recurrent stroke and not increase the risk of bleeding among patients with high risk transient ischemic attack ( tia ) or minor infarction23 ) due to our patient 's acute hemorrhage on the frontal convexity , we were concerned the hemorrhagic transformation and rebleeding because dual antiplatelet therapy ( clopidogrel plus aspirin ) was associated with a significant trend to increase moderate bleeding.17 ) so we treated with cilostazol plus aspirin successfully . the patient 's symptom was improved and there was no evidence of rebleeding on following studies . tan et al . reported that cilostazol , alone or with aspirin , decrease recurrence of ischemic stroke significantly , poststroke intracranial hemorrhage , and extracranial bleeding in patients with a prior ischemic stroke as compared with other antiplatelet treatments.21 ) cilostazol , a selective inhibitor of cyclic nucleotidephosphodiesterase 3 , increases activated intracellular cyclic adenosine monophosphate ( camp ) concentrations and thus inhibits platelet aggregation.19 ) cilostazol is a known direct arterial vasodilator,15 ) and has antiatherosclerotic effect,8 ) which can strengthen the endothelial barrier20 ) and additionally may play a role in neuroprotection.16 ) acute infarction with spontaneous convexal sah is rare but it is worth to work up to identify the etiology of csah using the cta or mra and mr image including t2 , dwi , swi . and we suggest that dual antiplatelet dugs ( cilostazole and aspirin ) are taken into account for treatments that improved the neurologic symptoms and reduced the concerns about stroke recurrence and rebleeding .

non - traumatic convexal subarachnoid hemorrhage ( csah ) is a comparatively infrequent with various vascular and nonvascular causes , it rarely occurs concomitant to acute ischemic stroke . we report a case of a 59-year - old woman , visited emergency room with right side subjective weakness spontaneously . magnetic resonance diffusion - weighted images revealed an acute infarction of anterior cerebral arterial territory . computed tomographic angiography showed a left frontal csah without any vascular lesions . and other laboratory studies were non - specific . we treated with dual antiplatelet drugs ( cilostazole [ otsuka pharmaceutical co. , ltd . tokyo , japan ] and aspirin [ bayer pharma ag . , leverkusen , germany ] ) . she has done well for a follow - up period . ( 5 months ) this case demonstrates the csah with acute infarction is rare but need to work up to identify the etiology and antiplatelet dugs are taken into account for treatments .

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mucus extravasation cysts or mucoceles are an extremely common lesion of the minor salivary glands . we report upon an unusual case of a submandibular gland mucocele presenting as a lateral neck swelling . the term plunging or cervical ranula refers to mucoceles that extend below the mylohyoid muscle , beyond the sublingual space and invariably are associated with the sublingual salivary gland . differentiation from submandibular gland mucoceles is potentially difficult , though plunging ranula is usually characterised by a so called tail sign on imaging . in our case a 54 year old woman presented with a large asymptomatic swelling of the right lateral neck . the swelling had been present for three months but had attained large dimension and was still felt to be increasing in size . she denied any history of trauma , surgery , infection , dysphagia , voice change or weight loss . palpation of the neck mass revealed a soft , fluctuant , non - tender swelling approximately 6 cm in diameter arising superficially within the right submandibular region . a magnetic resonance imaging ( mri ) scan revealed a large cystic structure in the right lateral neck involving the submandibular space ( fig 1 ) . the sample proved inadequate for cytological assessment , however was found to have a raised amylase and protein content suggesting salivary origin . mri scan showing cystic lesion within lateral neck under general anaesthesia the cystic mass was meticulously excised intact via a low submandibular incision . it was found to be in continuity with the ipsilateral submandibular gland ( fig 2 ) . histolopathology of the specimen confirmed a fibrous - walled retention cyst associated with a submandibular gland showing chronic obstructive changes . the patient made an uneventful post - operative recovery with no evidence of recurrence at six months . the presentation of a submandibular gland mucocele is uncommon with only a few reported cases in the literature ( 1 - 3 ) . it has been postulated that this rarity might be due to the anatomical location of the gland and the protective nature of the mandible1 . furthermore the physiology of the gland is such that unlike the sublingual gland , which exhibits continuous secretion , the submandibular gland secretes saliva only following stimulation ( 4 ) . nevertheless , despite the true aetiology being unknown it is thought likely that trauma , obstruction and congenital anomalies are most likely causes ( 5 ) . the differential diagnosis of a submandibular gland mucocele should include the numerous inflammatory , infective , developmental and neoplastic processes affecting the lateral neck . in particular , a solitary cystic mass should be thoroughly investigated to exclude the possibility of cystic degeneration of a lymph node secondary to metastatic squamous cell carcinoma . fine needle aspiration biopsy for cytological and biochemical assessment can confirm the nature of the cyst and is usually found to have a high amylase and protein content ( 6 ) . the management of a submandibular gland mucocele is potentially controversial and includes a number of treatment modalities that have been advocated in the management of the cervical or plunging ranula . injection of scelorosing agents have been used to induce inflammation and fibrosis from within the lumen of the cyst thus sealing further extravasation . aspiration is a simple technique but yields a high recurrence rate and as such its use has been largely restricted to the conservative management in the paediatric population . marsupialisation has gained popularity not least because of its relative simplicity , but also because it involves only limited dissection and therefore a reduced risk of damage to adjacent structures . recurrence however is unpredictable leading some authors to advocate a modified technique incorporating packing the cyst cavity ( 2 ) . contemporary opinion suggests that because mucoceles are pseudocysts there is no imperative to remove the cyst lining . appropriate management should focus on identification and elimination of the salivary gland responsible for the source of mucus secretion ( 1 ) . removal of the stimulus for secretion should cause involution of the cystic cavity , which seals itself , naturally ( 7 ) . we would advocate that in cases of a submandibular gland mucocele the lesion should be excised via a cervical approach in conjunction with the submandibular gland . if any doubt exists as to the close involvement of the sublingual gland then it would be advisable to remove this gland as well .

mucus extravasation cysts or mucoceles are an extremely rare occurrence in the major salivary glands . we report upon an unusual case of a submandibular gland mucocele presenting as a neck lump . it should therefore be considered in the differential diagnosis of swellings in the lateral neck . diagnosis and management are complicated by their similarity to the plunging or cervical ranula and differentiation may be potentially difficult . detailed imaging often reveals the plunging ranula as being characterised by a so called tail sign . in our case this sign was absent and subsequent excision confirmed origin from the submandibular gland . we discuss potential treatment modalities and propose a rationale for definitive management .

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heidelberger and his postdoctoral fellow forrest kendall who had been rendered one handed ( but , by all accounts , no less dextrous ) by a farm threshing machine took advantage of purified bacterial polysaccharides ( isolated during their earlier studies ) for their quantitative experiments . they incubated varying proportions of purified antigen and antibody and determined the nitrogen content ( i.e. , antibody content ) of the resulting precipitate . the data derived from these assays showed that the precipitin reaction could be expressed based on simple equations derived from the laws of mass action and that antibodies and antigens were multivalent . when they repeated the experiment with whole serum , their calculations held up , thus assuring them that their equations were not exclusively applicable to purified solutions ( 1,2 ) . this was all very well for antibodies to polysaccharides , noted heidelberger in a 1979 article , but what about those elicited by the vast numbers of protein antigens ? ( 3 ) . as n had not yet been discovered , heidelberger and kendall instead used a colorful trick to distinguish antigen - derived nitrogen from antibody - derived nitrogen . hen egg albumin against which they raised specific antibodies in rabbits ( 4 ) . the amount of antigen - derived nitrogen in the redissolved precipitate could then be determined by comparing its color ( by eye , as colorimeters did not yet exist ) with solutions containing known concentrations of the dye ; the remainder of the total nitrogen content was attributed to the antibody ( 5 ) . heidelberger later took on his first graduate student , elvin kabat . together , they helped settle a long - standing debate concerning whether serum precipitins and agglutinins ( antibodies that agglutinate bacteria ) were the same or different . at the time , many people thought that these distinct functional properties of antibacterial antiserum could be ascribed to separate entities . returning to the pneumococcal bacteria , the duo showed that precipitins and agglutinins were present in identical amounts in antipneumococcal serum . reduction of one activity by adsorbing the serum with a bacterial or polysaccharide solution resulted in an equivalent reduction in the other activity , suggesting that the two functions were properties of the same antibody molecules ( 6 ) . kabat went on to show that antibodies in serum came in two sizes large and small ( now known as igm and igg)based on their mass and sedimentation rate ( 7 ) . heidelberger 's work , said former colleague herman eisner ( massachusetts institute of technology ) in a 2001 article , changed the concept of the antibody from an essentially ill - defined set of serum activities to a protein molecule , measurable in conventional chemical units whose recognition of antigens could be analyzed in molecular terms heidelberger , who was also a talented musician and linguist , worked in the lab until his death at age 103 . at his 100th birthday party , he was reportedly asked how many papers he had published in his lifetime . three hundred and four , he answered , adding slyly , so far

having defined the protein nature of antibodies under the tutelage of oswald avery , michael heidelberger was the first to apply mathematics to the reaction of antibodies and their antigens ( the precipitin reaction ) . heidelberger 's calculations launched decades of research that helped reveal the specificity , function , and origin of antibodies .

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it is the 10th anniversary of the mailing of the anthrax spores , a tragic event that resulted in five deaths , seventeen other known infections , and untoward fear among the population . the cleanup is estimated to have cost $ 1 billion . what have we learned and accomplished in the interim of course , one can not consider the anthrax mailings in a vacuum , coming on the heels of the september 11 attacks on the world trade center , the pentagon , and united airlines flight 93 . the reaction from congress was swift : the united states patriot act was signed into law in october 2001 , and the public health security and bioterrorism preparedness response act followed in june 2002 . together , these pieces of legislation put restrictions and limits on who could access and possess select agents , those pathogens deemed by the cdc and usda to be the most dangerous . the government solicited studies from the national academies on various topics relating to science and security , other federal advisory panels were formed , and the government itself has addressed bioterrorism at various levels . numerous nongovernmental organizations throughout the world , including the american association for the advancement of science ( aaas ) , have also engaged scientists , security experts , ethicists , and others in an ongoing , fruitful discussion . while the specific charge to each of these groups differed , they all have addressed a common question : how do we ensure a vibrant research enterprise without compromising national security ? this question is of central importance given that the 21st century promises to be the biological century , which will likely spawn many new life science - based technologies and industries that will improve our lives . the answer to this question is not straightforward , mainly because of the nature of life science research . the risks that present themselves as a result of the acquisition of new knowledge are difficult to predict or quantify , while the potential benefits are more concrete . therefore , determining whether certain types of research should be prohibited or regulated is difficult . the consensus reached by both the scientific and national security communities is that research should proceed , with all involved being vigilant for the potential of misuse . the national science advisory board for biosecurity , which has been charged since 2005 with providing recommendations to the u.s . government on the oversight and conduct of dual use research , has developed a series of thoughtful reports that suggest a balanced approach to the topic ( see http://www.biosecurityboard.gov ) . perhaps the most important contribution of this body was to acknowledge that most if not all biological research had dual use capabilities while creating a special category known as dual use research of concern ( durc ) and the tools to identify it . this was important because it had the effect of walling off the small part of the scientific effort that was most relevant to the threat of bioterrorism and thus leaving the vast majority of biological research undisturbed and unregulated . another valid concern is whether certain individuals should not be allowed to access select agents . while some groups have now been excluded categorically by the above - mentioned statutes , vigorous discussions concerning personnel reliability in a broader sense insider threat was amplified by the identification of bruce ivins , a scientist working in a u.s . the emerging consensus is that ongoing attention to lab workers trustworthiness , behavior , and attitude is the best means to reduce the risk that someone might deliberately cause harm . what has the overall effect of these activities been on the life science research enterprise ? the infusion of extra research dollars has been welcome , especially at a time when federal funding of biology research overall has suffered . increased attention to the possible risk of misuse however , a small but significant number of investigators have chosen to discontinue working in the field due to the added regulatory burden . it is difficult to assess how many others are not entering into this area , but anecdotal evidence suggests this is occurring more than one would like . perhaps of greater concern is that important research , such as the development of new vaccines against anthrax , has been slowed by the need to work within the new regulatory and statutory framework . compliance with select agent rules has significantly increased the cost of research on certain pathogens ( 1 ) . the enactment of the select agent rules led to the destruction of several microbial collections ( 2 ) and is almost certainly interfering with the establishment of new collections or saving of new clinical isolates , given the enormous work involved in having such isolates transferred to secure facilities . furthermore , the focus on containing microbial threats by generating lists of organisms for special consideration may have created a false sense of security while greatly increasing the regulatory burden ( 3 ) . we are very fortunate that 10 years have passed with no additional bioterrorism events . this is a testament to the effort of scientists behaving responsibly and working together with the national security community to minimize the risks . while ideally , one would like to reduce the risk to zero , living in the real world , we know that zero risk would mean little progress and that an impaired research enterprise will leave us more vulnerable . our nation was built by , and has thrived on the efforts of , risk takers . the current oversight system for life science research is functional and robust , ensuring that the pace to discovery is limited only by intellectual and fiscal resources .

abstractin the fall of 2001 , bacillus anthracis spores were spread through letters mailed in the united states . twenty - two people are known to have been infected , and five of these individuals died . together with the september 11 attacks , this resulted in a reevaluation of the risks and benefits of life science research with the potential for misuse . in this editorial , we review some of the results of these discussions and their implications for the future .

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tetanus is a disease characterized by hypertonia and muscular spasms due to the toxin tetanospasmin formed by clostridium tetani . tetanus continues to be widespread , especially in the developing world though incidences have come down due to immunization . we present a case of tetanus in a young girl which initially mimicked a striatal toe though the potential cause of inoculation was trauma to nose . a 16-year - old girl presented with a history of sudden onset of pain in left leg with difficulty in walking for 2 days . an upturned big toe without fanning of other toes was seen on the left [ figure 1 ] . a clinical diagnosis of a striatal toe was made and the patient was admitted for further evaluation [ figures 1 and 2 ] . contrast - enhanced magnetic resonance imaging of the brain revealed no abnormality of the basal ganglia . liver function test was normal and slit lamp examination did not show a kf ring . corrected serum calcium was 9.8 mg / dl . on the 3 day after admission , she developed stiffness of bilateral lower limbs followed by episodic spasms of the back and neck . there were no signs of autonomic hyperactivity and she did not have any seizures . on further probing , patient 's mother revealed that she had suffered a fall a day before onset of her symptoms and hurt her nose . her mother said that she had received her primary series of tt in infancy and received her last booster 6 years back at around 10 years of age . she was given tetanus immunoglobulin ( tig ) 5000 units intramuscularly stat and also started on intravenous metronidazole and diazepam infusion . on the 5 day after admission , she developed mild trismus and opisthotonus completing the clinical picture of generalized tetanus . she started showing signs of recovery by day 10 and made a complete recovery in 3 weeks from onset of symptoms . tetanus is caused by the toxin tetanospasmin released by the germinating spores of the anaerobic gram - positive bacilli c. tetani . as spores of the bacilli occur in the soil , tetanus frequently occurs following a contaminated wound , but cases have also been reported after dental procedures , surgeries , burns , intravenous drug abuse , and intramuscular injections . our patient presented with a localized form of tetanus affecting initially the left leg that mimicked a striatal toe even though there was no local injury in the leg . it is possible that our patient had another insignificant trauma to her leg that had gone unnoticed . a striatal toe is a finding in clinical neurology that reliably localized the lesion to the caudate nucleus and putamen . the absence of fanning of the rest of the toes differentiates the upturned big toe from the babinski extensor plantar response . tetanus presenting initially with the classic clinical picture of striatal toe has not been reported before . thus , it is important to keep localized tetanus in the differential diagnosis of extrapyramidal disorders presenting with such spasticity , especially in the absence of definite history of trauma . dystonias can be ruled out in such cases by checking for resolution after a dose of benztropine . severity of tetanus can be graded according to the ablett classification into four grades . according to the ablett classification , the world health organization recommends a 5 dose schedule for tetanus vaccination while in india additional doses are recommended in the universal immunization program ( uip ) . our patient had received three doses as dtp in infancy and another dose between 12 and 24 months of age . she also had received two booster doses of dtp and td at 5 years and 10 years according to her mother as per the uip . the advisory committee on immunization practices of the centers for disease control does not recommend either td vaccination or tig for patients who have received more than three doses of tt with the last dose within 5 years . td is recommended in clean wounds with last booster > 10 years back and other wounds with last booster > 5 years back . tig should be given in unclean wounds when vaccination status is unknown or patient has received <3 doses . tetanus prone wounds are > 6 h old , > 1 cm deep , stellate , ischemic , denervated , contaminated or infected . our patient had received tt immunization at the time of primary wound care as per the recommendations . she did not receive tig as she had received more than 3 doses of immunization in the past . identification of vulnerable patients by testing for protective tetanus antibodies is not viable in our setting . this may be due to a defect in the patients humoral immunity due to which she could nt mount an antibody response . rapid bedside tests to screen for tetanus immunization status have been found to be more effective than medical interview and wound assessment in some studies , but cost effectiveness remains an issue . wound care , antimicrobial therapy with metronidazole and human tig are cornerstones of therapy of established tetanus . a full course of active immunization with tt should be started early as neither clinical infection nor tig provide long - term immunity . cases of tetanus continue to come to medical attention in spite of widespread immunization in this age and time . we must be alert to the possibility and institute prompt treatment after a clinical diagnosis as early passive immunization reduces morbidity and mortality .

we report the case of a 15-year - old girl who was initially diagnosed to have a striatal toe . her condition progressed and she later developed clinical features consistent with tetanus . history of blunt trauma to nose was elicited retrospectively . antimicrobial therapy with metronidazole and both active and passive immunization was started immediately . the patient went on to make a complete recovery .

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idiopathic hypereosinophilic syndrome ( he s ) is a condition of unknown origin characterized by clinical manifestations attributable to eosinophilia and eosinophilic infiltration of tissues . cardiac involvement is rare and threatening accounting for 33% to 43% of death in he s . management of pregnant patients with he s is challenging and rarely been reported , particularly in the setting of heart failure . a 29-year - old woman returning from saint martin island presented in april 2013 with dyspnea and chest pain , which were then diagnosed as clinically suspected eosinophils - associated myocarditis because of pulmonary edema , elevated troponin , and high eosinophils blood count . she received 3 pulses of steroids and was also treated with 2 doses of ivermectine as strongyloides serology was positive . in july 2013 , troponin dosage , eosinophils blood count , echocardiography , and cardiac magnetic resonance imaging ( mri ) were normal . in december 2013 , when she was pregnant with 18 weeks of amenorrhea ( wa ) , she was admitted to the intensive cardiology unit department for respiratory distress . blood tests showed elevated ultrasensitive troponin : 139 ng / ml ( n < 0.14 ) , nt - probnp : 3350 ng / l , and markedly increased circulating eosinophils at 4.75 10/l . renal and liver tests were normal . a transthoracic echocardiogram revealed hyperkinetic left ventricular with subtotal thrombotic occlusion of left ventricle ( lv ) ( figure 1c and e ) . cardiac mri revealed diffuse lv endomyocardial fibrosis with circumferential intraventricular adherent lv thrombus ( figure 1a ) . no extra - cardiac involvement ( i.e. , neurological , pulmonary , cutaneous , or gastrointestinal ) was detected . screening for all etiology of secondary or clonal eosinophilia was negative including extended lymphoid phenotyping , janus kinase 2 mutation ( jak2 ) , and factor interacting with papola and cpsf1 ( fip1l1)-type platelet - derived growth factor receptor ( pdgfra ) transcript fusion testing . ( a ) four - chamber view during cine acquisition after gadolinium injection shows subendocardial enhancement of the left ventricle ( lv ) with a large adherent thrombus inside the ventricular cavity . ( d and f ) echocardiogram findings 6 month after delivery showing complete disappearance of lv thrombus and normal lv ejection fraction . symptomatic treatment included diuretics , low - dose -blockers , and curative anticoagulation with enoxaparin . three intravenous pulses of 1 g methylprednisolone were administrated followed by 1 mg / kg / d of oral prednisone . she quickly improved , keeping a class iii new york heart association ( nyha ) dyspnea . despite persistent severe postcapillary pulmonary hypertension one month later , echocardiography was stable and eosinophils were still at 1.0 g / azathioprine was introduced ( 2 mg / kg / d ) and steroids were progressively tapered down . the newborn 's weight was 1900 g ( between 10th and 25th percentile ) , and birth blood ph and lactate were 7.26 and 3 under azathioprine , 6 months after delivery , she was asymptomatic , and eosinophils blood count as well as echocardiography and cardiac mri had normalized ( figure 1 ) . here we described a case of severe eosinophilic endomyocardial fibrosis occurring during pregnancy . under treatment with steroids and azathioprine , despite severe pulmonary hypertension , pregnancy had a favorable outcome . acquired eosinophilia is classified as secondary ( parasitic , drug - induced , vasculitis , ) , clonal ( myeloid or lymphoid malignancies , ) , or idiopathic . after exclusion of secondary causes of eosinophilia , a stepwise diagnostic algorithm should include peripheral blood screening for fip1l1pdgfra transcript fusion , bone marrow biopsy , jak2 mutation testing , peripheral blood lymphocytes phenotyping , and t - cell receptor gene rearrangement studies in order to discard clonal causes of eosinophilia . the diagnostic of he s can be advocated in case of negativity of all the test cited above . cardiac involvement of he s is rare and life - threatening , accounting for 33% to 43% of deaths , with a frequency reported from 5% to 72% . treatment of chronic acquired eosinophilia strongly depends on whatever the cause of eosinophilia . in clonal he s , corticosteroids remain the first - line treatment and corticosteroid - sparing agents nowadays mainly rely on hydroxyurea , interferon- , or cyclosporine . despite a promising preliminary study , mepolizumab and other anti - interleukin-5 antibodies no specific drugs have been advocated in cardiac involvement of he s except for heart failure treatment and anticoagulation therapy because of the high frequency of intracardiac thrombus . the use of azathioprine as a corticosteroid - sparing agent for he s has been only anecdotally reported without clear information about its efficacy . only 3 cases of pregnancy during he s have been reported , all with favorable outcomes . two patients were treated with steroids ( maintenance doses between 20 and 25 mg / d ) and the last one was left untreated . one of those patients had a cardiac involvement consisting in right and lv thrombus but without cardiac failure . the persistence of pulmonary hypertension and elevated circulating eosinophils counts led us to introduce a corticosteroid - sparing agent , namely , azathioprine , because of the safety profile during pregnancy . six months after delivery , echocardiography and cardiac mri confirmed full resolution of interventricular thrombus with regression of endomyocardial fibrosis . in conclusion , even in a severe cardiac involvement of he s , pregnancy can successfully be conducted using steroids and azathioprine . this study has been approved by the ethics committee : comit de protection des personnes ( cpp ) ile - de - france vi , the authors would like to thank professor david grant for his help in editing the manuscript .

abstractidiopathic hypereosinophilic syndrome ( he s ) is a condition of unknown origin characterized by clinical manifestations attributable to eosinophilia and eosinophilic infiltration of tissues . cardiac involvement is rare and threatening accounting for 33% to 43% of death in he s . management of pregnant patients with he s is challenging and have rarely been reported , particularly in the setting of heart failure.we here report on the case of a 29-year - old woman with he s who developed severe endomyocardial fibrosis with heart failure during pregnancy . outcome was favorable under treatment with prednisone and azathioprine.this case illustrates a favorable outcome of endomyocardial fibrosis during pregnancy .

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this study was a controlled clinical trial aiming to compare the outcomes of open reduction and rigid internal fixation of displaced calcaneal fractures with that of non operative treatment . the research proposal of this study was approved by research department of isfahan university of medical sciences . from december 1998 until january 2009 , 72 patients with displaced intra - articular calcaneal fractures admitted in kashani university hospital and were randomly allocated to surgical and non surgical groups . first group underwent open reduction and internal fixation with reconstruction plate and screws fixation and the other group were treated with closed reduction and cast immobilization.13 data were collected by clinical observation and a questionnaire six months following surgery . some reasons that patients were not selected for surgery were as follows : patient disagreement with surgery , open fractures ( not suitable for open reduction internal fixation ) , combined injuries ( head trauma , cardiovascular disorders , severe osteoporosis ... ) also were not suitable for surgery179 and severe comminution . post - operative exam after two weeks , one month , three months , six months and one year was recorded . roentgenography was obtained and physical examination including pain scoring , swelling , limitation of activities , shoe wearing difficulties , range of motion and osteoarthritis in ankle and subtalar joints as well as patient satisfaction were also scored and recorded . functional scoring based on kerr 's meta - analysis and pain scoring was used.1121 data were analyzed by spss 18 software . seventy two patients with mean age 49 years ( 21 - 84 years old ) were included . eleven patients were excluded from the study ( unable to follow up after hospital discharge ) . eventually , 61 cases of calcaneal fractures enrolled and were also followed - up for averagely 3 years . patients in operation group sub - classified in two categories : first group comprised of 17 cases with essex - lopresti technique ( under fluoroscopy - x - ray control , closed reduction , internally fixed with pin fixation , and cast immobilization).22 second group consisted of 14 cases with open reduction with lateral calcaneal approach and fixation with reconstruction plate ( figure 4 ) . ambulation with crutch walking and non - weight bearing continued for 6 - 10 weeks after surgery . lateral calcaneal approach with exostosectomy thirty cases had non - surgical treatment , with splinting , ice pack , elevation the limb , then short leg cast and ambulation with crutch walking and non weight bearing . in non - surgery group ambulation with crutches started 3 days after casting and cast was removed after 6 weeks and physical therapy , home exercises and partial weight bearing was recommended . the findings regarding the comparison between two groups for different variables are shown in table 1 . fracture classification ( sander s ) in post operation examinations , range of motion of ankle in both groups were good ( more than 50% of r.o.m ) but in subtalar joints decreased range of motion in non - operative group compared to operative group was obtained ( odds ratio : 6.75 , p = 0.002 ) . last x - ray examinations showed that traumatic osteoarthritis ( degenerative joint disease ) in non - operative group was a major problem ( 26% compared to 9% in operative group ) . shoe fitting difficulties was also a major problem ( 50% in non - operative compared with 12% in operative group).18 pain in walking was 63% in conservative group compared to 29% in operative group ( odds ratio : 6.72 , p = 0.001).2122 swelling in ankle and foot , reflex sympathetic dystrophy including focal osteoporosis and or spotty osteoporosis in non operative group was twice more than operative group ( 6 cases versus 3 cases ; odds ratio : 6.80 , p = 0.001 ) ( table 2 ) . our findings showed that open reduction and internal fixation of displaced calcaneal fractures in absence of open fracture , severe osteoporosis , or comminution and poor general condition may be the preferred method of treatment . although surgical treatment of calcaneal fractures has recently received attention owing to good results and less morbidities,13911 most of orthopaedic surgeons prefer to treat them conservatively , probably because of many complications including post operative infections , wound dehiscence , malreductions and long term osteoarthritis . most of calcaneal fractures are intra - articular and displaced . on the other hand , many of these fractures have ecchymosis , swelling , and blister which increase risk of open reduction and internal fixations ( fracture- blister).14 thornes et al.15 showed that surgically treated calcaneal fractures have better prognosis compared with those conservatively treated . burdeaux 's work also showed that shoe fitting and weight bearing difficulties were less in those underwent operation.16 pain in daily living activities were dramatically less in patients with open reduction and internal fixation , and range of motion in ankle and subtalar joints were desirable.1720 open reduction and internal fixation of displaced calcaneal fractures in absence of open fracture , severe osteoporosis , or comminution , poor general condition may be the preferred method of treatment . young and middle aged patients with calcaneal fracture who are in sander 's type ii and iii with mild comminution due to minor trauma , without soft tissue injuries may be the best candidates for open reduction and internal fixation . mhn and fmm participated in the design study , conduct the study and prepared the manuscript .

background : the aim of this study was to compare outcomes of open reduction and rigid internal fixation of displaced calcaneal fractures with that of non operative treatment.methods:seventy two consecutive patients with displaced intra - articular calcaneal fractures were selected regarding inclusive and exclusive criteria and then were randomly allocated to surgical and non surgical groups . first group underwent open reduction and internal fixation with reconstruction plate and screws fixation and the other group were treated with closed reduction and cast immobilization . data were collected by clinical observation and a check list . data was analyzed by chi - square and student 's t-test.results:the results showed significant difference between outcomes of surgical treatment and nonsurgical method ( p = 0.001 ) . there were some differences between two methods in terms of decreasing pain [ odd ratio ( or ) : 6.72 , p = 0.001 ] , swelling ( or : 6.80 , p = 0.001 ) , increased range of motion of the joints ( p = 0.001 ) , decreased late osteoarthritis ( or : 2.33 , p = 0.22 ) in favor of surgical group.conclusions:open reduction and internal fixation of displaced calcaneal fractures in absence of open fracture , severe osteoporosis , or comminution , poor general condition may be the preferred method of treatment .

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the presence of oral synechia along with cleft palate is a rare syndrome . we encountered a case of cleft palate accompanied by congenital lateral oral synechia the infant was delivered normally at full term with a low birth weight of 1,750 g. there were no particularly notable points in the family history , medical history , or reproductive history . on examination , the patient had a restricted mouth opening resulting from congenital oral synechia due to membranous adhesion between the free margin of the cleft palate and the floor of the mouth , lateral to the tongue on the left side . the congenital oral synechia appeared as a thin membrane with a broad attachment at the floor of the mouth measuring approximately 2 cm in anteroposterior width . at the palatal margin the attachment narrowed to about 0.5 cm [ figure 1 ] . congenital lateral synechia the infant faced feeding problems due to the restricted mouth opening , and therefore an immediate surgical excision of the synechia was decided on . feeding was done using an infant feeding tube till anesthetic clearance was obtained for the procedure . at 1 week after birth , the congenital synechia was excised under sedation uneventfully restoring adequate mouth opening and allowing normal feeding [ figure 2 ] . the first report of oral synechia was by illera in 1875 , but the first documented case of a lateral synechia between the floor of the mouth and free margin of cleft palate was by hayward and every in 1957 . over the years , almost 60 cases of oral synechia have been reported out of which 52 are lateral synechia and 8 were of the median variety . these can be classified into five types : synechia by cord - like adhesion of the alveolar mucosa on one or both sides of the upper and lower jaw ( alveolar synechia ) ; synechia by a membranous adhesion on the hard palate and floor of the mouth , excluding the rear of the tongue ( lateral synechia ) ; synechia in which the hard palate and tongue are partially involved ; synechia in which the soft palate and tongue are widely involved , such that continuity is interrupted between the oral cavity and the pharynx ; and synechia by a membranous adhesion between the hard palate and lower lip . , reported that five family members had cleft palates and synechia , one having a cleft palate without synechia , and one transmitted the gene but did not express it . the etiology of intra - oral bands or synechia of epithelial tissue has been debated , but many theories have been proposed . during the 7 to 8 week of embryological development , the alveolar ridges , tongue , and palatal shelves are in contact with each other . the ensuing palatal closure depends on downward contraction of the tongue . when the tongue protrudes from the mouth as a result of medial movements of the oral cavity walls , it prevents the alveolar ridges from fusing . genetic , teratogenic , or mechanical insults during this critical stage may lead to periods of close , quiescent contact between oral structures , and this predisposes to abnormal fusion . longacre asserts that oral synechia is due to the persistence of the buccopharyngeal membrane , and is for that reason associated with micrognathia and cleft palate . kruger speculates that the mechanical effect of the tongue may contribute to cases in which the periphery of the cleft palate adheres to mucous membranes on the floor of the mouth , and that adhesion in cases of cleft palate may occur as a result of obstruction by the tongue . according to mathis , when adhesion of the palatal shelf occurs during developmental stages , adhering epithelial rudiments , for some reason , lead to synechia . the general consensus on the treatment of cleft palate lateral synechia syndrome is excision of the synechia and palatal closure . dalal et al . , have reported a case of intra alveolar synechia in two siblings , one of whom had a spontaneous resolution of the adhesion . have documented that the synechia provided additional tissue for surgical closure with less tension on the palatal flaps . we believe that such a use of the synechia has been possible , because the membranous adhesion in this case had fibromuscular bands in it unlike our situation where the synechia consisted of thin membranous tissue of unequal width . the conventional oro - tracheal intubation or the use of a laryngeal mask may not be possible due to the presence of the synechia . fiberoptic nasotracheal intubation may not be feasible due to technical difficulties of finding a bronchoscope small enough for a week old infant . performing a procedure on the highly vascular floor of the mouth under local anesthesia in an infant where immediate excision of the synechia is deemed necessary either due to breathing or feeding problems , sedation can be used under constant anesthetic monitoring for the surgical procedure as was done in our case .

cleft lip and palate are the most common congenital craniofacial anomaly in humans . the presence of oral synechia along with cleft palate is a rare syndrome . we encountered one case that had a cleft palate accompanied by congenital oral synechia due to a membranous adhesion between the floor of the mouth and the free margin of the cleft palate .

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the mayer - rokitansky - kster - hauser ( mrkh ) syndrome or mullerian duct agenesis is characterized by congenital aplasia of the uterus and the upper part ( 2/3 ) of the vagina in women showing normal development of secondary sexual characteristics and a normal 46 , xx karyotype . till date the presence of alopecia with mrkh syndrome is a mere coincidence or an associated finding is a subject of research and may require further evidence . a 17-year - old girl presented with hair loss from the scalp for 1 year . the loss of hair begins at the occipital area of the scalp , and it progressed along the lateral margins of the scalp in a band like fashion clinically suggestive of ophiasis type of alopecia areata . detailed gynecological examination revealed normal secondary sexual characters with well - developed external genitalia and hypoplastic vagina [ figure 1b ] . the histopathology of the scalp revealed lymphocytic infiltration around the lower third of the hair follicle , a finding suggestive of alopecia areata . to rule out the cause of amenorrhea , ultrasonograhy of abdomen and pelvis was done which revealed the absence of uterus and right kidney with normal ovaries [ figure 2a and b ] . hormone levels ( follicle - stimulating hormone , luteinizing hormone , estradiol , testosterone , and thyroid function test ) were within normal limits . clinical findings shows ( a ) ophiasis type of alopecia areata , ( b ) well - developed external genitalia and hypoplastic vagina ultrasonography of abdomen and pelvis shows ( a ) absence of uterus , ( b ) absent right kidney the detailed review of four case reports of mrkh syndrome with alopecia in world 's literature has been given in table 1 . first , three reports were from the same geographical region of middle east ( jordan , lebanon , and turkey , respectively ) . hypothesized that the founder mutation in middle east population might be responsible for the condition to be restricted to that geographical region . however , the fourth case report from south asia ( pakistan ) questioned the hypothesis of founder mutation leading to mrkh syndrome restricted to that geographical region . we are reporting the fifth case report which is the second case report from south asia and first among indian population . our case report is another evidence to suggest that mrkh syndrome with alopecia is not restricted to middle east population . review of literature of mrkh syndrome with alopecia in all previously reported four case reports , there was a history of parental consanguinity and siblings were also affected with mrkh syndrome and alopecia . in our case , there was no history of parental consanguinity and siblings were normal . there are many case reports and syndromes of hypogonadism with alopecia . in all the previous case reports of mrkh syndrome with alopecia , hypergonadotropic hypogonadism was noted . this case is the first report of mrkh syndrome with alopecia with normal gonadal function . mrkh syndrome may have associated abnormalities such as renal agenesis , skeletal abnormalities , hearing loss , or cardiac defects . in our case , the right renal agenesis was the associated finding of mrkh syndrome with alopecia which is not observed in all the previous four case reports under review . in a female patient of alopecia areata , history of primary this syndrome is caused by embryologic growth failure of the mullerian duct with resultant agenesis or underdevelopment of the vagina , uterus or the both . all the reported cases of mrkh with alopecia including our case had alopecia areata which is an autoimmune disease . there seems to be no direct correlation between these entities as one is due to a genetic defect , and other is an autoimmune disease . hence , the presence of alopecia in the case of mrkh syndrome is a mere coincidence , or an associated finding of the syndrome is a matter of further study . the authors certify that they have obtained all appropriate patient consent forms . in the form the patient(s ) has / have given his / her / their consent for his / her / their images and other clinical information to be reported in the journal . the patients understand that their names and initials will not be published and due efforts will be made to conceal their identity , but anonymity can not be guaranteed . the authors certify that they have obtained all appropriate patient consent forms . in the form the patient(s ) has / have given his / her / their consent for his / her / their images and other clinical information to be reported in the journal . the patients understand that their names and initials will not be published and due efforts will be made to conceal their identity , but anonymity can not be guaranteed .

a 17-year - old girl presented with alopecia involving lateral margins of the scalp with primary amenorrhea . there was no history of parental consanguinity , and no other siblings were having similar complaints . her secondary sexual characters were well developed with hypoplastic vagina . histopathological findings from scalp biopsy showed features of alopecia areata . ultrasonography of abdomen and pelvis revealed the absence of uterus and the right kidney . follicle - stimulating hormone , luteinizing hormone , estradiol , testosterone , and thyroid function test was within normal limits . the patient had normal 46 , xx karyotype . till date , only four case reports of mayer - rokitansky - kster - hauser ( mrkh ) syndrome with alopecia has been reported . we are reporting the first case of mrkh syndrome with alopecia with normal gonadal function in world 's literature .

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coronary artery fistula ( caf ) is an unusual coronary artery abnormality , where connection exists between coronary artery and cardiac chamber or another blood vessel . caf originating from the left main trunk and left circumflex artery is very unusual and rarely reported in the literature . we describe a case of giant left main trunk and left circumflex artery fistula to the right ventricle . a 24-year - old male patient presented with complaints of dyspnea and palpitation during exercise . on physical examination , his blood pressure was 120/80 mmhg and pulse rate was 75 bpm . the heart was rhythmic and chest auscultation revealed a continuous murmur of grade 3/6 at the upper left sternal border . transthoracic echocardiography ( tte ) showed enlargement of the left main trunk and left circumflex coronary artery , with a 25-mm inner diameter , diffusely tortuous dilated and drained into the posterior wall of the right ventricle [ figure 1 ] . left anterior descending artery , right coronary artery , and major side branches were normal . the left ventricular systolic function was normal with an ejection fraction of 65% and there were no abnormalities in the regional wall motion and cardiac valves . laboratory investigations were normal . in order to further evaluate the fistula in more detail , a 320-slice dynamic volume ct ( aquilion one , software release v. 4.3 , toshiba medical systems , japan ) angiogram was performed , using 3-dimensional volume - rendered ( vr ) and curved - plain reconstruction ( cpr ) . it demonstrated a large fistula arising from the left main trunk and left circumflex artery emptying to the right ventricle [ figure 2 ] . color - doppler echocardiography revealed enlarged and tortuous of lm and lcx ( white arrows ) origin from ao , abnormal flow from ao passing lm and lcx to rv through a fistula ( red arrow ) . ( ao : aorta , lm : left main trunk , lcx : left circumflex artery , lv : left ventricle , rv : right ventricle , ra : righe atrium , la : left atrium ) contrast - enhanced ct coronary angiogram . 3-dimensional volume - rendered ( vr ) and curved - plain reconstruction ( cpr ) shows origin and course of the fistula . the vessel runs from the left main trunk and left circumflex coronary artery and drained into the posterior wall of the right ventricle through a fistula ( red arrow ) . ( ao : aorta , lm : left main trunk , lcx : left circumflex artery , lv : left ventricle , rv : right ventricle ) congenital caf is caused by a cardiovascular abnormality in embryo period , which accounts for 0.27 - 0.40% of all congenital cardiac defects . acquired caf has been described after surgical procedures , endomyocardial biopsy , trauma , inflammation , atherosclerosis , and collagen vascular disease . caf usually drains into the right chamber , pulmonary artery , pulmonary veins , superior vena cava , inferior vena cava , and coronary sinus . most caf patients are usually asymptomatic and are found incidentally during angiographic evaluation for other cardiac diseases . clinical symptoms of patients with caf are dependent on the size of fistula and the pressure of its terminal chamber . in our patient , the giant caf increases the volume load of the right heart chambers and the pulmonary artery . if the shunt of caf is significant , steal blood phenomenon may occur and cause myocardial ischemia or infarction , which increases risk of infective endocarditis , accelerates atherosclerosis , and even heart failure . generally , tte is an important primary non - invasive tool for diagnosis of coronary artery abnormality and confirmed by coronary angiography . with the cardiac ct technological improvement in recent years , particularly in temporal / spatial resolution and reduced radiation dose , coronary computed tomography angiography ( ccta ) has been a relatively new imaging modality and non - invasive method for assessment of coronary artery disease . ccta not only precisely demonstrate the origin , course , and drainage site of the fistula , but also provides surgical plan for treatment . it is suggested that caf should be treated as soon as possible to avoid the potential risk of complications , no matter whether clinical symptom exists or not . in our case , he experienced no serious cardiac events over half a year of follow - up . in conclusion , the giant left main trunk and left circumflex artery fistula to the right ventricle are rarely seen .

coronary artery fistula including the left trunk and left circumflex is uncommon . we present a 24-year - old male patient with a giant left main trunk and left circumflex artery to right ventricle fistula , which is diagnosed by transthoracic echocardiography and coronary computed tomography angiography . in this paper , the case report is to provide a better understanding of clinical characteristics for this disease .

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a 60-year - old man was presented to an orthopedician in the operating theatre as a case of difficult urinary catheterization . the patient was going for a lengthy orthopedic operation that required a drained urinary bladder beforehand . the urologist was called and he found the patient anesthetized , having circumcised penis and a pin - hole external urethral meatus ( eum ) at the corona penis level . the tight meatus was negotiated first with a lubricated 4-french ( fr ) bougie urethral dilator followed by subsequent sized dilators up to 14- fr caliber when a proper foley catheter was introduced easily into the bladder . the patient was carefully interviewed to reveal that circumcision was performed neontally as a religious rite , and he has no history of urologic diseases or trouble voiding , as this was the first time for him to meet a urologist . the patient , who is unaware of his condition , is a father of 12 children and never underwent urinary catheterization . hypospadias is a highly prevalent congenital anomaly of the male genitalia . in comprehensive review , sorensen ( 1953 ) credited rennes in 1831 with reporting a prevalence of hypospadias of 1 in 300 recruits and also reported the same figure for live male births in denmark . there is a plethora of hypospadias cases of different degrees of severity repaired in childhood that resulted in different psychological , social , and sexual outcomes . psychosexual effects of hypospadias repair are endured in adulthood although affected men maintain satisfaction in their sexual life . it is unusual in the sense that the elderly man should have had his hypospadias deformity repaired decades ago in order to pass urine freely and to impregnate his spouse with a wider , and properly located meatus . the tight meatus in this case was severe , hardly admitting a lubricated 4-fr bougie dilator . litvak et al . , reported that the meatus in children younger than one year accepts a lubricated 5-fr feeding tube . they also reported that , in children aging 1 - 6 years , an 8-fr feeding tube could pass without difficulty . the social and sexual life of adults operated for hypospadias during childhood has been studied by a few authors . a few publications reported patient and partner dissatisfaction with the appearance of genitalia , as sexual dissatisfaction is often attributed to penile size and curvature . noted that self - reported strength of libido was slightly better for controls compared to patients with hypospadias , but without a statistically significant difference . noted that only about 10% of both patients and controls reported that their libido was low . problems reported include weak or dribbling ejaculation , having to milk out ejaculate after orgasm , quantity of semen passing after intercourse , anejaculation with or without orgasm . liu et al . observed that the rates of ejaculation problems in the distal and proximal groups were 19.5% ( 8/41 ) and 48.6% ( 17/30 ) , respectively [ 5 , 6 ] . the erectile problems in repaired hypospadias may be attributed to surgically correctable and non - correctable causes . more commonly encountered correctable causes include persistent chordee , penile torsion , fistula formation , acquired meatal stenosis , and inadequate cosmetic outcome . similarly , in unrepaired cases , as the eum is distal enough to deposit the seminal fluid high in the posterior vagina with no difficulty , fertility is supposed to be preserved . furthermore , aho et al . found that men who had hypospadias during childhood were less likely to live with a partner , and that they had fewer children ( 0.8 vs. 1.1 ) . figure 1 extremely tight external meatus in a fairly asymptomatic 60 yrs , old man with distal hypospadias . the literature is scant about the urinary , social , sexual , and fertility aspects of unrepaired hypospadias cases . to our knowledge , no other case has been reported for a circumcised uncorrected hypospadias with extremely tight eum in a the finding in this treatise supports the previously published data surrounding the unaffected sexual and fertility aspects of patients having distal hypospadias , and limits repair to cosmetic reasons .

hypospadias is a highly prevalent congenital anomaly . english articles , indexed in pubmed , published the long - term sexual and reproductive outcome following hypospadias repair . almost all repairable cases of hypospadias are operated in childhood . although distal hypospadias does not interfere with fertility , it is worthy reporting a case of an elderly man , who fathers 12 children and has no urologic complaint , presented with unrepaired coronal hypospadias and severely tight external urethral meatus .

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mesenchymal breast neoplasms are rare . sarcoma is a heterogeneous neoplasm arising from mesenchymal cells . breast sarcomas are rare neoplasms derived from non- epithelial elements of the gland and represent < 1% of all breast cancers estimated as 45 new cases per 10 million women . most cases of breast sarcoma are secondary to radiotherapy due to increasing use of breast radiation after breast - conserving treatment . about 1 of 300 patients receiving radiotherapy for breast cancer can be expected to develop sarcoma . only a few hundred cases of breast sarcomas have been reported in the literature making the diagnosis difficult . we present a rare case of lymphatic metastases of primary spindle cell sarcoma of the breast . forty - three per cent occur in the extremities with two - thirds of them in the lower limb and one - third in the upper limb . thirty - four per cent of sarcomas are intra - abdominal consisting of 19% visceral and 15% retroperitoneal lesions . several histological subtypes of breast sarcomas have been described as case series or case reports due to the multiple different cells present in the mesenchymal tissue of the mammary gland , such as endothelial , muscle and fat cells . the most common subtypes are malignant fibrohistiocytoma , fibrosarcoma , angiosarcoma and spindle cell sarcoma . less common subtypes are liposarcoma , leiomyosarcoma , rhabdomyosarcoma , osteosarcoma , synovial sarcoma , neurosarcoma , stromal sarcoma , chondrosarcoma and hemangiopericytoma . angiosarcomas appear to be the commonest histological subtype in radiation - induced sarcomas of the breast [ 4 , 5 ] . the main risk factor for the development of breast sarcomas is previous radiation treatment for breast carcinoma and non - hodgkin 's lymphoma . other recognized factors are chronic lymphoedema , exposure to vinyl chloride and artificial implants as well as li - fraumeni syndrome through a p53 mutation . a 45-year - old healthy caucasian female patient presented in the emergency department with sudden onset of left breast erythema . on examination , she had an oedematous , tender , erythematous left breast with areas of blistering , epidermolysis and necrosis . an ultrasound scan revealed the presence of gas and fluid - filled pockets . the laboratory risk indicator for necrotising fasciitis score can be utilized to risk stratify patients presenting with signs of cellulitis to determine the likelihood of necrotizing fasciitis . a score > 6 of 13 indicates that necrotizing fasciitis should be seriously considered . in this case , a score of 8 was allocated for serum sodium of 126 mmol / l , haemoglobin of 6.6 g / dl and c - reactive protein of 306.7 mg / l . her other biochemical markers were normal , including serum creatinine of 68 mol / l , plasma glucose of 8.8 mmol / l and a leukocyte count of 11.5 10/l . a provisional diagnosis of necrotizing fasciitis was made , and the patient was referred to the breast surgeons . the histopathology demonstrated that the breast was partially replaced by a partly cystic and partly solid necrotic lesion . a microscopic examination showed an atypical undifferentiated spindle cell lesion with a fascicular architecture , pleomorphism and marked mitotic activity with areas of ulceration and necrosis ( figs 1 and 2 ) . the initial set of immunostains performed showed that tumour cells were negative for cytokeratins ( fig . 3 ) , s100 and lca . the tumour cells showed diffuse and strong vimentin positivity ( fig . further immunocytochemical labelling showed weak expression of cd99 , patchy strong expression of cd10 and patchy weak expression of smooth muscle actin . cytokeratins ( cam 5.2 ) and ema were expressed and there was no tumour - specific expression of cd34 , desmin or myogenin . fluorescent in - situ hybridization analysis failed to demonstrate evidence of a t(x:18 ) translocation using the lys - syt break apart probe . the diagnosis of a grade 3 undifferentiated spindle cell sarcoma was made and although the tumour was reported to have a clear resection margin ( 5 mm ) in most areas , the presence of necrosis and granulation tissue reaching the deep margin made the status of the margin uncertain . figure 1:photomicrograph 4 h&e ; spindle cell tumour with areas of haemorrhage and necrosis . figure 2:photomicrograph 40 h&e ; pleomorphic spindle cells in fascicles with several mitoses . computed tomography scan demonstrated left axillary lymphadenopathy and a small left - sided basal effusion . following discussion of the case at the multidisciplinary meeting , radical completion mastectomy was recommended . reconstruction was with a split thickness skin graft by the plastic surgery team prior to her radiotherapy treatment ( fig . necrotizing fasciitis is a highly lethal infection that causes rapidly spreading necrosis of fascia and subcutaneous tissues , sometimes involving muscle and skin . treatment is with haemodynamic support of sepsis , broad spectrum antibiotics , intravenous immunoglobulin and extensive debridement . following debridement in this patient , sections from the specimen demonstrated an undifferentiated spindle cell sarcoma with areas of haemorrhage and necrosis , contrary to the initial presentation of presumed necrotizing fasciitis . the treatment for breast sarcomas is planned by a multidisciplinary team and follows the treatment model of sarcomas in other locations . localized tumours should be treated by complete excision , while mastectomy should be performed for more sizeable tumours . adequate surgical excision seems to be one of the most important prognostic factors along with the tumour 's diameter and grade . axillary dissection is unnecessary for breast sarcomas , as they rarely metastasize via the lymphatic system . while chemotherapy is the mainstay of treatment for advanced systemic disease , radiotherapy has a role in lymphatic metastasis and preventing loco - regional recurrence . the reported 5-year survival in patients with breast sarcomas varies between 40 and 91% in different studies .

breast sarcomas are rare neoplasms arising from the few epithelial elements of the gland . it represents much < 1% of all breast cancer . of the heterogeneous group of sarcomas , the more common subtypes include spindle cell sarcoma . the main risk factor for the development of breast sarcomas is previous radiation therapy following breast - conservation surgery for breast cancer or non - hodgkin 's lymphoma . we report on an idiopathic presentation of spindle cell sarcoma in an otherwise healthy middle - aged woman . an emphasis is made on the rare occurrence of lymphatic metastasis . we discuss our recommended management strategy with particular reference to the benefit of multidisciplinary team decision - making .

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address = administration of drotrecogin alfa ( activated ) in early stage severe sepsis ; apache = acute physiology and chronic health evaluation ; drotaa = drotrecogin alfa ( activated ) ; prowess = recombinant human activated protein c worldwide evaluation of severe sepsis . jf was involved with the conception and design of the study , acquisition , analysis and interpretation of data , and wrote the first draft of the manuscript . na was involved with the conception and design of the study , analysis and interpretation of data , and critical revision of the manuscript for important intellectual content . mm was involved with the interpretation of data and critical revision of the manuscript for important intellectual content . relative risk ( rr ) and 95% confidence intervals ( 95% ci ) for 28-day mortality in each study . n / n = number of deaths at 28 days divided by the total number of patients randomly assigned to drotrecogin alfa ( activated ) or placebo . for the phase ii trial , only patients who were randomized to the same dose and duration of drotrecogin alfa ( activated ) used in the recombinant human activated protein c worldwide evaluation of severe sepsis ( prowess ) and administration of drotrecogin alfa ( activated ) in early stage severe sepsis ( address ) trials are included . results are classified by low - risk and high - risk subgroups from the recombinant human activated protein c worldwide evaluation of severe sepsis ( prowess ) and administration of drotrecogin alfa ( activated ) in early stage severe sepsis ( address ) trials , defined by either acute physiology and chronic health evaluation ( apache ii ) score ( less than 25 , and 25 or more ) or organ failure ( single and multiple ) . weight refers to the contribution of each study to the overall pooled estimate of treatment effect for each low - risk and high - risk subgroup . the weight of each study is calculated as the inverse of the variance of the natural logarithm of its relative risk . the size of the symbol denoting each point estimate approximates the weighting of each study to each pooled effect measure . each pooled effect measure is calculated with the use of a random - effects model . n / n = number of deaths at 28 days divided by the total number of patients in each particular subgroup randomly assigned to drotrecogin alfa ( activated ) or placebo . the numbers of patients and deaths at 28 days in each subgroup were estimated from data provided in references , and for the prowess trial , and in references and for the address trial .

two international multicentre randomised controlled trials of drotrecogin alfa ( activated ) ( drotaa ) , the recombinant human activated protein c worldwide evaluation of severe sepsis ( prowess ) and administration of drotrecogin alfa ( activated ) in early stage severe sepsis ( address ) trials , have produced inconsistent results . when 28-day mortality data from these trials for patients with severe sepsis and at high risk of death are pooled using a standard random - effects meta - analysis technique , there is no statistically significant survival benefit ( for patients with acute physiology and chronic health evaluation ( apache ii ) scores of 25 or more ) , or a borderline significant benefit ( for patients with multi - organ failure ) . we argue that two important methodological issues might explain the disparate results between the two trials . these issues centre on early trial stopping , which exaggerates treatment effects , and reliance on subgroup analyses , which for drotaa yields inconsistent results across different definitions of high risk . these concerns call into question the effectiveness of drotaa in any patients with severe sepsis . consequently , further randomised trials of this agent in prospectively defined high - risk patients are required to clarify its role in the management of severe sepsis .

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gram - positive infections account for up to 50% of cases of severe sepsis in the modern intensive care unit . the complex processes by which gram - positive organisms cause sepsis are poorly understood by comparison with gram - negative sepsis . much interest is currently focused on the role of certain protein exotoxins synthesized by staphylococcus aureus and streptococcus pyogenes , which share the immunological property of being super - antigens . superantigens are characterized by the ability to bypass normal major histocompatibility complex ( mhc)-restricted , intracellular , antigen processing and presentation . through direct binding to the mhc class ii molecule and the t cell receptor , at sites away from those involved in conventional antigen binding , superantigens activate up to 50% of the whole t cell repertoire rather than the 1% fraction stimulated by conventional antigens . such toxins are , however , believed to have a role in causation of two classic superantigen - mediated diseases , staphylococcal and streptococcal toxic shock syndromes , that kill 5000 americans per annum . they may also contribute to the pathogenesis of other forms of gram - positive shock . in addition to intensive care support and antimicrobial therapy , various adjunctive treatments for toxic shock syndrome have been evaluated both in vitro and in clinical trials ( table 1 ) . nevertheless , the treatment of toxic shock syndrome , like that of conventional forms of sepsis , remains suboptimal and the disease is still associated with mortality in the region of 50% and associated with considerable morbidity . they identified a dodecapeptide that is highly conserved among different bacterial superantigens and lies in a region of the super - antigen molecule away from sites involved with either mhc class ii or t cell receptor interaction . several modified forms of this peptide acted as antagonists to a range of bacterial superantigens against which they were tested in vitro . one dodecapeptide , which was a particularly effective antagonist , was administered to mice challenged with bolus doses of bacterial superantigen . arad et al speculate that the mechanism of inhibition may involve co - stimulatory pathways of t cell activation . interestingly , protection against subsequent challenges , at 3-weekly intervals , improved with each challenge . this improved protection correlated with antibody production against the whole challenge superantigen , while antibody against the dodecapeptide was not detected . this finding is in keeping with the previously observed correlation between lack of antibody against streptococcal pyrogenic exotoxin a and development of invasive s. pyogenes infection . one consequence of the cytokine storm induced by superantigens may be to disrupt the development of antibody - mediated immunity . by switching off superantigenicity , the dodecapeptide may be allowing normal antibody production to occur . although the prospect of drugs to switch off superantigenicity is exciting , there have been many false dawns in the field of sepsis research . all laboratory animals are intrinsically resistant to the effects of bacterial superantigens . the mouse model , while being one of the best established systems for studying toxic shock , requires far higher doses of superantigen than are needed to induce shock in humans , and prior ' sensitization ' of the animal with the hepatotoxin d - galactosamine . we have recently demonstrated , in a mouse model of invasive streptococcal infection , that other properties of these toxins may be more important than their superantigenicity and , paradoxically , such effects may in fact be advantageous to the host . furthermore , administration of bolus doses of superantigen probably does not reflect the pattern of toxin production in clinical cases . certain findings of the report by arad et al are at odds with our current understanding of bacterial superantigens . the study found that animals protected from one super - antigen in an initial challenge were cross - protected against different superantigens in subsequent challenges . this effect was observed for toxins as dissimilar as staphylococcal exotoxin b and toxic shock syndrome toxin 1 , which have only 6% sequence homology . this is hard to understand in terms of neutralizing antibody since no cross - reactivity between toxic shock syndrome toxin 1 and other superantigens has been demonstrated in serological or neutralization assays . the paper by arad et al is the first published report of superantigen antagonist peptides . encouragingly , at least one other group is making progress in the same area , and have demonstrated a protective effect not only against bolus doses of superantigen , but also in a model of co - challenge with endotoxin . further studies to address the mode of action of these peptides , particularly in super - antigen - sensitive animal models ( sriskandan et al , manuscript submitted ) , are necessary before speculation about clinical trials is warranted . specific approaches to treatment of toxic shock syndromes spea , streptococcal pyrogenic exotoxin a ; spec , streptococcal pyrogenic exotoxin c.

the production of superantigenic exotoxins by gram positive bacteria underlies the pathology of toxic shock syndrome . future treatment strategies for superantigen - mediated diseases are likely to be directed at blocking the three - way interaction between superantigen , t cell receptor and major histocompatibility class ii molecule , which inititates an excessive and disordered inflammatory response . in this article , we review the first published data to address one such strategy in the context of other recognised and experimental treatments .

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endometriosis is a common gynaecological condition characterised by the presence of endometrial glands and stroma at extrauterine sites . ectopic endometrial implants have been reported in nearly every tissue or organ , including the skin . of the reported cases of cutaneous endometriosis , over 70% the case of primary cutaneous endometriosis described here remains a rare entity with a reported incidence of 0.51% of all extragenital endometrial ectopia . in december 2012 , a 31-year - old caucasian woman presented to the dermatology outpatient clinic with a 1-month history of a persistent , raised lesion in the umbilicus . the patient had noted swelling and one episode of spontaneous frank bleeding from the lesion . there was no associated cyclical pain at the lesion site . at the time of examination , a single firm 0.5-cm black - coloured papule was seen within the umbilicus at the 3 o'clock position . no discharge or underlying umbilical hernia was noted . the patient had a history of 2 previous melanomas : the first in 2003 on the left abdomen and the second on the right buttock in 2006 . given the anatomical location , a skin punch biopsy of the umbilical lesion was performed . during dermatology review , 1 month later , it was noted that 3 distinct skin - coloured papules had appeared next to the initial lesion ( fig . histological examination of the punch biopsy revealed a lesion in the superficial dermis comprising a single dilated glandular structure , surrounded by cellular endometrial - type stroma ( fig . the gland was lined by a single layer of columnar cells , a few of which had apical cilia . subsequent gynaecological evaluation revealed a 3-year history of dysmenorrhoea . a provisional diagnosis of coexistent pelvic endometriosis was made . a diagnostic and therapeutic laparoscopic examination was advised if the patient remained unable to conceive over the following 6 months . less than 30% of cutaneous endometriosis appears in the absence of a prior surgical history and is termed spontaneous ( primary ) cutaneous endometriosis . of these cases , umbilical endometriosis characteristically occurs in women of reproductive age , who present with an umbilical nodule at the site of a prior surgical incision associated with cyclical pain at the lesion site . however , the inconsistent appearance and rarity of this phenomenon means it is often clinically misdiagnosed . endometriomas under the skin have been described as red , blue , black or flesh - coloured . classic associated symptoms include cyclical pain , discharge , bleeding or swelling of the lesion correlated with the menstrual cycle . the most widely accepted pathogenesis of secondary endometriosis is the iatrogenic implantation of endometrial cells as a result of surgery , commonly laparoscopic procedures . however , the pathogenesis of primary endometriosis remains uncertain . theories suggested include the implantation of cells through sanguineous or lymphatic spread , or differentiation from coelomic pluripotent cells in the skin . the heterogeneity in the clinical presentation of cutaneous umbilical endometriosis reflects the breadth of differential diagnoses that may mimic the condition ( table 1 ) . malignancies , in particular melanoma and umbilical metastasis of visceral carcinoma ( sister mary joseph nodule ) , must be considered . distinctive dermatoscopic , ultrasonographic and magnetic resonance imaging findings have been described ; however , histopathological examination remains the gold standard . hormonal therapy in the form of gonadotropin - releasing hormone agonists , oral contraceptives and danazol may be given preoperatively to reduce the size of lesions and ameliorate symptoms consistent with pelvic endometriosis . subsequent gynaecological evaluation for pelvic endometriosis is recommended for all patients . around 15% of patients diagnosis of the umbilical skin lesion facilitated the provisional diagnosis and management of underlying symptomatic pelvic endometriosis . of note , the patient in this case study has a strong history of melanoma . recent data have reported a statistically significant association between endometriosis and the occurrence of melanoma . further studies are required to examine the possible association of cutaneous endometriosis and the development of melanoma . in summary , nevertheless , it should be considered in the differential diagnosis when examining any umbilical lesion , even in absence of pathognomonic cyclical symptoms .

cutaneous endometriosis that arises de novo , without a prior history of surgery , is a rare phenomenon . the clinical diagnosis of cutaneous endometriosis remains challenging due to the variable clinical appearance and symptoms of the condition , and therefore must be considered in the differential diagnosis of any umbilical lesion . we report a 31-year - old woman who presented with spontaneous cutaneous endometriosis of the umbilicus .

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causes of anisocoria include compression or destruction of the third cranial nerve by increased intracranial pressure ( icp ) from tumour , thrombus , oedema , aneurysm or haemorrhage . cases of anisocoria have rarely been reported in the postoperative intensive care unit ( icu ) setting . we report a case of anisocoria in icu that was in all likelihood linked to the vulnerability of brain with old traumatic brain injury ( tbi ) to regional increase in icp secondary to general anaesthesia and intraoperative fluid resuscitation . a 45-year - old male with severe acute pancreatitis ( sap ) was referred to the icu with acute physiology and chronic health evaluation ( apache ii ) score 20 and intra - abdominal hypertension . about 5 years back , he had had a tbi ( marshal grade iii ) with significant intracranial bleed . it was a focal lesion and he had a complete clinical recovery with conservative management . after surgical necrosectomy performed in the sixth week of sap , there was fresh bleeding from the drains requiring an urgent re - exploration . his haemoglobin dropped from 10 gm% to 6 gm% within few hours , and his prothrombin time was 6 s prolonged , with a platelet count of 60,000/cmm . the intraoperative period was uneventful from the point of adverse events like hypoxia , hyperventilation , severe hypotension ( mean blood pressure < 60 ) or hypertension . however , he required significant volume resuscitation ( about 5 l in 2 h ) comprising of 1.5 l of crystalloid solution , 0.5 l of colloid solution , 4 units of packed red blood cells ( prbc ) , 4 units of fresh frozen plasma ( ffp ) , 10 units of random donor platelet and 10 units of cryoprecipitates , to maintain haemostasis and haemodynamics . soon after shifting him back to the icu a negative pilocarpine test ruled out adie syndrome and he did not exhibit features of horner 's syndrome . absence of any appreciable localizing sign was suggestive of a nonvascular major intracranial event as the cause of acute anisocoria . in the background of existing coagulopathy , but , an urgent computed tomography scan revealed an old , healed haemorrhage in the left fronto - temporal region as sequelae to the past tbi and no new organic lesion or bleed [ figure 1 ] . soon thereafter , interventions were started to decrease icp and 1 g / kg intravenous bolus mannitol and 20 mg frusemide were administered . repeat doses were given every 4-hourly for 24 h and he was nursed in the head - up position . within 12 h of initiating measures for icp reduction , hypertension and bradycardia resolved and his left pupil started to decrease in size and reaction to light was restored . after normalization of pupillary size and response to light , mannitol and frusemide were stopped . on day 3 of the event , he was fully conscious and his trachea was extubated . anisocoria during general anaesthesia has been reported mostly during induction of anaesthesia on account of parasympathetic dominance by anaesthetic drugs such as thiopental , midazolam , isoflurane and vecuronium induced autonomic tone disturbance.[37 ] lazar et al . reported that midazolam can cause a brief ischemic event in the left cerebral hemisphere in patients with an associated abnormality of the left side of the brain . although thiopental , midazolam , isoflurane and vecuronium were administered in our patient , anisocoria appeared during recovery from general anaesthesia and not during the induction period . the triad of acute onset hypertension , sinus bradycardia and anisocoria is suggestive of regional increase of icp . easy reversibility of the triad after a short period of mannitol and frusemide therapy also justifies the transient rise in regional icp as cause of anisocoria in our case . haemodynamically , volume resuscitation of 5 l in a short period of 2 h was well tolerated by the patient and the central venous pressure ( cvp ) never went beyond 10 mmhg . following tbi , an increased cvp occurring with aggressive crystalloid resuscitation may contribute to the loss of brain compliance and the development of intracranial hypertension . in our case , this was probably not the underlying mechanism . rather , tbi has been reported to give rise to latent occult cryptic vascular lesions . we postulate that an old tbi may render a brain vulnerable to a regional increase in icp during active fluid resuscitation , which may also get influenced by the autonomic tone disturbance secondary to drugs like thiopental , isoflurane and vecuronium by the following mechanisms : clinically latent occult cryptic vascular lesions may persist for an unidentified period after tbi.these cryptic vascular lesions may have much autoregulatory dysfunction.such lesions may cause regional elevation of icp during fluid resuscitation with or without general anaesthetics . clinically latent occult cryptic such lesions may cause regional elevation of icp during fluid resuscitation with or without general anaesthetics . although anisocoria has been considered as a benign event in a critical care patient , our case suggests that anisocoria in a subset of the population may actually be an impending neurologic emergency . authors think it appropriate to believe that one should exert extra caution about the rapidity of fluid resuscitation in the management of a case of old tbi . also , it may be advised that fluid resuscitation in such patients is accompanied by concomitant pupillary examination .

anisocoria is an uncommon entity in general postoperative intensive care . we present a case of a 45-year - old man suffering from severe acute pancreatitis with a past history of traumatic brain injury ( tbi ) , who developed hypertension , bradycardia and anisocoria soon after re - exploration surgery under general anaesthesia . computed tomography showed no new lesion . measures directed towards reducing intracranial pressure resulted in amelioration in about 12h . the possible role of old tbi in the causation of anisocoria during general anaesthesia and resuscitation has been explored in this report .

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in january 2015 , two sisters aged four ( sibling 1 ) and six ( sibling 2 ) with asymptomatic , consanguineous ( first cousin ) parents were referred to our ophthalmology department for evaluation of bilateral high astigmatism . both siblings suffered since birth from poor vision in both eyes and photophobia since birth . on ophthalmological examination , autorefractometer measurements for sibling 1 and sibling 2 were od 3.75 2 179/os 3.75 2.75 177 and od 2.25 7.75 166/os 3.75 5.75 174 , respectively . reliable visual acuity measurements could not be obtained in sibling 1 , whereas best - corrected visual acuity for sibling 2 was 20/32 . blue sclera and mild globular protrusion of the cornea were observed bilaterally in both siblings . slit - lamp examination of the cases revealed that both corneas were globular in shape with peripheral corneal thinning . corneal topography and pachymetry maps were obtained using a scheimpflug imaging ( pentacam , oculus optikgerte gmbh , wetzlar , germany ) [ fig . 1 ] . maximal keratometry ( kmax ) indices for sibling 1 and sibling 2 were 52.9 d ( od)/53.5 d ( os ) and 54.4 d ( od)/55.4 d ( os ) , respectively . the corneal thickness values for sibling 1 and sibling 2 were 241 ( od)/291 ( os ) and 286 ( od)/305 ( os ) , respectively . corneal topographic images of the left eye of sibling 1 showing limbus - to - limbus corneal thinning the two siblings had in common the features of keratoglobus , blue sclera , atypical faces , hearing loss , and hypermobile joints [ fig . 2 ] . therefore , they were referred to the genetic department for systemic evaluation . on general assessment both siblings had flat midfaces , large eyes , frontal bossing , mild hypertelorism , calvarial thickening , and absent frontal sinuses , suggesting a diagnosis of marshall syndrome [ fig . 3 ] . these siblings had also mandibular hypoplasia , hyperextensible joints , and metaphyseal widening of long bones , suggesting a diagnosis of stickler syndrome . otoacoustic emission test was performed to evaluate hearing loss and was found abnormal in both siblings . other detailed clinical characteristics of marshall syndrome , stickler syndrome , and our cases are presented in table 1 . we tentatively diagnosed the sisters as having an overlapping marshall / stickler phenotype based on clinical and radiological findings . frontal and profile views of sibling 1 ( top ) and 2 ( bottom ) absence of frontal sinus is seen in x - ray graphy of sibling 2 clinical features of marshall syndrome , stickler syndrome , and overlapping phenotype of our cases written informed consent was taken for photography and genetic analysis . we could study only the exon 49 and exon 52 regions of the col11a1 gene , and the results were negative . protective eyeglasses were prescribed for both siblings , and avoidance of contact sports was highly recommended owing to the high risk of perforation . to our knowledge , this is the first report describing congenital keratoglobus with blue sclera in two siblings with overlapping marshall - stickler phenotype . in the past , it is proposed that the existing phenotypic overlap suggests that marshall and stickler syndromes are probably allelic expressions of the same locus . although jun et al . demonstrated the expression of the col11a1 gene in human donor corneas , corneal disease associated with marshall - stickler syndrome due to col11a1 mutation has not yet been reported . the altered collagen due to col11a1 mutation may weaken collagen fibers in the cornea , which could play a role in the development of keratoglobus in these cases . furthermore , thinning and breakdown of the collagen is the main histological finding in cases of blue sclera . in practice , there are difficulties in obtaining whole genome analysis due to size and complexity of the col11a1 gene and also to the high cost of these investigations . only the exon 49 and exon 52 regions of the col11a1 gene were identified and found to be mutation negative . furthermore , we could not screen the col2a1 gene in relation to some forms of stickler syndrome . khalifa et al . pointed out that dominant and recessive mutations in the col11a1 gene cause marshall and stickler syndromes . in this report , our cases were the offspring of unaffected consanguineous parents , suggesting autosomal recessive inheritance . our cases also showed bilateral involvement . in the literature , keratoglobus with blue sclera was reported in association with connective tissue disorders . these disorders are ehlers - danlos type vi , marfan syndrome , rubinstein taybi syndrome , and osteogenesis imperfecta . until now , keratoglobus with blue sclera has not been reported in association with marshall / stickler phenotype . as a connective tissue disorder , marshall - stickler syndrome might be in the differential diagnosis of keratoglobus with blue sclera . the authors certify that they have obtained all appropriate patient consent forms . in the form the patient(s ) has / have given his / her / their consent for his / her / their images and other clinical information to be reported in the journal . the patients understand that their names and initials will not be published and due efforts will be made to conceal their identity , but anonymity can not be guaranteed . the authors certify that they have obtained all appropriate patient consent forms . in the form the patient(s ) has / have given his / her / their consent for his / her / their images and other clinical information to be reported in the journal . the patients understand that their names and initials will not be published and due efforts will be made to conceal their identity , but anonymity can not be guaranteed .

we aimed to describe congenital keratoglobus with blue sclera in two siblings with overlapping marshall / stickler phenotype . two sisters ( ages four and six ) with bilateral high astigmatism were evaluated by slit - lamp microscopy . corneal topography and pachymetry maps were also obtained . slit - lamp examination revealed that both corneas were globular in shape with peripheral corneal thinning . pachymetry maps showed diffuse corneal thinning . two siblings had in common the features of keratoglobus , blue sclera , atypical face , hearing loss , and hypermobile joints . we tentatively diagnosed the sisters as having an overlapping marshall - stickler phenotype based on clinical and radiological findings . marshall - stickler syndrome may exist in the differential diagnosis of keratoglobus with blue sclera .

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immune checkpoint inhibition with anti - ctla-4 blockade ( e.g. , ipilimumab ) and anti - pd-1 antibodies ( e.g. , nivolumab ) has improved the poor prognosis of unresectable malignant melanoma [ 1 , 2 ] . these newly approved medications induce many types of immune - related adverse events ( iraes ) , including pneumonitis , colitis , hepatitis , and endocrinopathies such as hypophysitis and thyroiditis . although iraes induced by ipilimumab have occasionally been reviewed in the literature , studies on nivolumab are also gradually being described . a 52-year - old male with lung and liver metastasis of malignant melanoma was put on nivolumab therapy ( 3 mg / kg every 3 weeks ) . after approximately 34 weeks of nivolumab administration ( fig . 1 ) , laboratory tests revealed a sudden elevation of liver enzymes ( ast / alt ) to 1,225/824 u / l ( grade 4 ) . computed tomography detected the exacerbation of liver metastasis , identifying a lesion that was slightly larger than the nondiffuse , localized lesion that had been observed 3 months earlier ( fig . 2 ) . therefore , we suspected hepatitis associated with nivolumab because this drug has a low probability of causing serious liver damage to localized lesions , even when they are large . the patient stopped taking nivolumab and was treated with 70 mg / day ( 1.0 mg / kg / day ) of systemic corticosteroids . his ast / alt level promptly improved to 112/389 u / l within 3 days . the median onset of ipilimumab - related hepatitis is approximately 812 weeks after initial treatment . therefore , the interval from nivolumab initiation to the occurrence of hepatitis was much longer than that reported in previous cases . hepatitis induced by nivolumab was also observed at 712 weeks in a pooled analysis of a nivolumab phase iii trial . however , the incidence of grade 23 nivolumab - induced hepatitis was approximately 1% in a phase iii clinical study . in that study , the liver function test improved to grade 1 within 415 days of initiation of corticosteroid treatment . the liver dysfunction caused by long - term nivolumab therapy in this case is noteworthy . although many diseases induce liver dysfunction , in this case , we definitively excluded other causes of hepatitis such as viral infection ( e.g. , hbv , hcv , hsv , cmv , and ebv ) , medication other than nivolumab , and other forms of autoimmune hepatitis . to manage hepatitis associated with nivolumab , these possibilities must be excluded as causes of the disease . the recommended initial treatment of hepatitis in the risk evaluation and mitigation strategy ( rems ) is to administer systemic corticosteroids ( 12 mg / kg / day of prednisone ) . if the symptoms continue after 35 days , alternative immunosuppressive therapy , such as 500 mg of oral mycophenolate mofetil every 12 h , must be considered . in this case , because the laboratory test showed an ast / alt level > 20 the upper limit of normal , we considered systemic corticosteroids to be the most appropriate treatment . fortunately , the ast / alt level rapidly improved to grade 12 in 3 days , and modification was not necessary . it is very important to note that severe hepatitis can occur despite long - term nivolumab therapy . in this case , it was possible to quickly reach a correct diagnosis because we were aware of the possibility of drug - induced hepatitis , even though the period of occurrence of nivolumab - induced hepatitis had passed . therefore , we believe that this report may be very informative when treating hepatitis as an irae of nivolumab . in addition , to our knowledge , this patient exhibited the longest time between nivolumab administration and the onset of hepatitis that has been reported to date .

immune checkpoint inhibitors have drastically changed in the treatment of many kinds of malignancies , especially malignant melanoma . the focus of the recent experiments has not only been on their efficacy but also immune - related adverse events ( iraes ) . we report a case of fulminant hepatitis due to nivolumab . in this case , the patient had undergone long - term nivolumab therapy . he did not complain of any symptoms but his liver enzyme levels were extremely elevated ( grade 4 ) . we promptly decided to start oral corticosteroids in the patient . his liver function rapidly improved . the dose of corticosteroids was gradually reduced . our case demonstrates that sudden onset fulminant hepatitis can occur despite the safe use of long - term nivolumab therapy . the irae can improve rapidly with proper corticosteroid treatment . this report will be useful for the physicians who always use immune checkpoint inhibitors .

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the management of critically ill patients with a suspected invasive fungal infection based on predefined clinical and microbiological criteria or the punctuation of a score may be a valid approach when the definitive diagnosis is feasible only in a small proportion of patients . this is what vandewoude and colleagues propose with their retrospective analysis of all patients who had aspergillus spp . fungal infections have increased in intensive care units ( icus ) over the past decades . although less common than candidiasis , aspergillosis is more likely to result in a life - threatening infection . thus , neutropenic patients , and those who receive long - lasting corticosteroid treatments , are at high risk for invasive aspergillosis . this organism grows on a wide variety of organic material and the conidia are easily aerosolised . although exposure is universal , invasive infection occurs almost entirely in immuno - suppressed individuals . outbreaks have been described in bone marrow transplantation , solid organ transplant recipients and leukaemia patients in association with hospital construction and/or ventilation system contamination with aspergillus . indeed , multiple organ failure and prolonged stays in the icu are associated with a complex decrease in immune functions , deactivation of macrophages and altered cellular response . this is usually not feasible given the special circumstances of critically ill ventilated patients . likewise , screening the blood for galactomannan may be very valuable in neutropenic patients but its usefulness in icu patients is limited . before new antifungal agents were available , mortality of critically ill patients with invasive aspergillosis was nearly 100% . currently , the therapeutic armoury has significantly improved with the introduction of new azoles ( i.e. , voriconazole ) and the echinocandins ( i.e. , caspofungin ) , a new class of drugs with a novel target . many problems contribute to the lack of confident and timely diagnosis of invasive aspergillosis in critically ill patients . on one hand , the early administration of antifungal agents may be life - saving , but clinicians must also bear in mind the problems and costs associated with needless treatments derived from the overinterpretation of the potential clinical significance of isolates of aspergillus spp . in respiratory samples . propose a clinical algorithm based on the criteria defined by an international conference on the diagnosis of aspergillosis in immunocompromised patients . with this approach , approximately 50% of the patients were diagnosed with invasive aspergillosis and in the other 50% the isolation was considered colonization . unfortunately , histology was available only in a small proportion of patients ( one - fourth of patients with presumed diagnosis of infection and one - tenth of the patients with the diagnosis of colonization ) . at first glance , these results seem very hopeful , although positive and negative predictive values can not be calculated with these figures . the diagnostic accuracy of this algorithm can be improved . many authors have documented that invasive aspergillosis can occur in certain types of ' non - immunocompromised ' critically ill patients . three high risk groups stand out for invasive aspergillosis : chronic obstructive pulmonary disease , prolonged multiple dysfunction syndrome in the situation of immunoparalysis , and severe hepatic failure . these underlying conditions are not included in the proposed criteria and they should be added to the list . this may avoid the misclassification of these high risk patients if semiquantitative culture of bronchoalveolar lavage was not positive , a criterion not universally accepted . moreover , a high resolution ct scan is nowadays mandatory and a normal portable chest x - ray may lead to an erroneous classification . the significance of a positive respiratory culture for aspergillus spp . in a non - immunodepressed patient causes the clinician great uncertainty and doubt . nowadays , the isolation of aspergillus spp . in a critically ill patient is not an exceptional curiosity . definitions proposed by the european organisation for the research and treatment of cancer were not designed to guide clinical practice . critical care physicians need a helpful instrument to decide in which circumstances antifungal therapy should be initiated early , given the high mortality of this infection but the availability of new and active agents . obviously , this and other strategies need to be validated in large cohorts of critically ill patients before they can be recommended . this is an urgent task because we do not expect to have at our disposal a precise microbiological test in the near future .

the clinical relevance of recovering aspergillus species in intensive care unit patients is unknown . diagnosis of invasive pulmonary aspergillosis is extremely difficult because there are no specific tests sensitive enough to detect it . the rapidly fatal prognosis of this infection without treatment justifies early antifungal therapy . a clinical algorithm may aid clinicians to manage critically ill patients from whose respiratory specimens aspergillus spp . have been isolated . this new tool needs to be validated in a large cohort of patients before it can be recommended .

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by using a previously described dna restriction analysis procedure ( 7 ) , we studied 76 archived adenovirus isolates collected among influenzalike - illness surveillance sites across iowa from 1992 to 2002 . among the 76 isolates , 40 ( 53% ) were ad7d2 , and 6 ( 8% ) were ad7h ( figure ) . the first ad7d2 specimen was isolated in march 1994 from a child living in south - central iowa . the first ad7h specimen was isolated in november 1993 from a child living in north - central iowa . number of adenovirus ( ad ) isolates collected in iowa during influenzalike - illness surveillance by genome type and year . ad7d2 caused illness among patients in iowa ranging in age from 3 months to 49 years . although the clinical details are sparse , a number of patients were thought to have influenza or were diagnosed with respiratory distress syndrome . at least 4 children from an ad7d2 october 2000 epidemic at a long - term care facility in des moines , iowa , died . ad7d2 became increasingly more prevalent across iowa , displacing ad7b , the predominant genome type circulating in the united states since the early 1970s ( 8) . in 2002 , data suggest that ad7d2 supplanted all other ad7 genome types ( 9 of 9 ad7 isolates were a7d2 ) ( figure ) . ad7d2 was first detected in israel in 1992 ; beginning in 1995 , it was associated with epidemics of unusually severe respiratory disease with high fevers among children in japan ( 9,10 ) . ad7h was first detected in south america in 1986 ; since then it has supplanted the previous most prevalent genome type , ad7c , in chile , uruguay , argentina , and possibly other countries ( 11 ) . ad7h has caused pediatric respiratory epidemics , and infected children had longer hospitalizations , had higher temperatures , and required more supplemental oxygen ( 12 ) . in at least 1 study , up to 94% of adenovirus deaths were attributed to ad7h ( 11 ) . whether these strains are truly more virulent or whether they better evade the host s immune system is a matter for future study . what does seem to be clear is that a simple mutation ( ad7d2 ) ( 9 ) or recombination ( ad7h ) ( 13 ) may generate new adenovirus strains that could result in more epidemics and higher death rates . the number of immunocompromised patients in the united states is increasing , and they , in addition to young children , may be at increased risk for severe disease from emergent adenovirus strains . developing molecular typing strategies for emerging ad strains seems prudent , as does improving local and national surveillance for adenovirus illness . considering adenovirus to be a potential nosocomial pathogen seems wise , and researchers should seek to identify effective antiviral therapy for outbreak interventions . these actions will help public health officials better understand the changing epidemiology of adenovirus infections . because of increased adenovirus morbidity ( 14,15 ) , the u.s . department of defense recently contracted to again produce ad4 and ad7 vaccines for military trainees . if civilian populations were identified to be at high risk for serious ad4 or ad7 disease , they might also benefit from these vaccines .

we evaluated 76 adenovirus type 7 ( ad7 ) isolates collected in iowa from 1992 to 2002 and found that genome type ad7d2 became increasingly prevalent . by 2002 , it had supplanted all other ad7 genome types . the association of ad7d2 with severe illness and death calls for heightened public health concern .

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funding for travel or speaker honoraria : ( 1 ) istanbul ms days , novartis pharmaceuticals , speaker honoraria payment to mayo clinic . no personal compensation . ( 2 ) invited professor program , biogen - boston , speaker honoraria payment to mayo clinic . no personal compensation . other activities : grant review for the national multiple sclerosis society . research support , commercial entities : dr . orhun h. kantarci receives research support from the european regional development fund ( fnusaicrc cz.1.05/1.1.00/02.0123 ) , the national multiple sclerosis society , and has given a scientific presentation at a meeting supported by teva pharmaceuticals but has received no personal fees or personal compensation for this activity ( all compensation for consulting activities paid directly to mayo clinic ) nor has spoken about the specific medications involving this company . kejal kantarci ( spouse ) serves on the data safety monitoring board of takeda global research and development center , inc . , and the data monitoring boards of pfizer inc . and janssen alzheimer immunotherapy and is funded by the nih ( r01 ag040042 [ pi ] , r21 ns066147 [ pi ] , p50 ag44170/project 2 [ pi ] , p50 ag16574/project 1 [ pi ] , r01 ag11378 [ co - i ] , u19 ag10483 [ co - i ] u01 ag042791 [ co - i ] ) and minnesota partnership for biotechnology and medical genomics ( po03590201 [ pi ] ) . kejal kantarci serves on the data safety monitoring board of takeda global research and development center , inc . , and the data monitoring boards of pfizer inc . and janssen alzheimer immunotherapy and is funded by the nih ( r01 ag040042 [ pi ] , r21 ns066147 [ pi ] , p50 ag44170/project 2 [ pi ] , p50 ag16574/project 1 [ pi ] , r01 ag11378 [ co - i ] , u19 ag10483 [ co - i ] u01 ag042791 [ co - i ] ) and minnesota partnership for biotechnology and medical genomics ( po03590201 [ pi ] ) kejal kantarci serves on the data safety monitoring board of takeda global research and development center , inc . janssen alzheimer immunotherapy and is funded by the nih ( r01 ag040042 [ pi ] , r21 ns066147 [ pi ] , p50 ag44170/project 2 [ pi ] , p50 ag16574/project 1 [ pi ] , r01 ag11378 [ co - i ] , u19 ag10483 [ co - i ] u01 ag042791 [ co - i ] ) and minnesota partnership for biotechnology and medical genomics ( po03590201 [ pi ] ) . research support , foundations and societies : 20062009 multiple sclerosis society for support in multiple sclerosis research unrelated to this publication ; 20082009 mayo foundation cr20 award for support in multiple sclerosis research unrelated to this publication ; 20092011 hilton foundation support in multiple sclerosis research unrelated to this publication .

before the genomics technology revolution allowed us to do genome - wide science , genetics research relied on our limited knowledge about a subject to generate hypothesis and candidate genes to study . despite the level of naivet , several associations with susceptibility to a complex disease such as multiple sclerosis ( ms ) were discovered . of these , hla - drb1 and il7r1 stand out as being confirmed and refined early by the genome - wide association studies ( gwas ) that followed.2 despite the expense and gargantuan efforts , these gwas have successfully led to the discovery of more than 100 additional genes , albeit with smaller effect sizes , that contribute to ms susceptibility.3 this list keeps growing , but it comes with no surprise that most of these genes identified the immune system as one large candidate for ms susceptibility .

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plasmacytoid urothelial carcinoma is a rare malignant neoplasm in the urinary bladder recognized by recent who classification of urothelial carcinoma . it is an aggressive variant associated with poor prognosis that presents at an advanced clinical stage . limited data is available about the pathological , immunohistochemical characteristic as well as clinical behavior of this rare variant . morphological distinction from other malignant neoplasms with plasmacytoid phenotype is critical for its clinical management . treatment remains a challenge because of late presentation of the disease and presence of metatstasis at the time of initial work up.[27 ] we present here a case of 54-year - old male patient who was referred to our hospital for diagnostic work - up of bladder cancer . ct scan of abdomen and pelvis showed thickened urinary bladder wall with irregularity of the mucosa involving entire bladder . radical cystectomy was done which on gross examination showed a grey white firm to hard , ill - circumscribed ulcerative tumor involving almost the entire bladder measuring 2 cms in thickness . microscopic examination showed a high - grade tumor composed of discohesive plasmacytoid cells replacing the lamina propria [ figures 1 and 2 ] . the tumor cells were seen extending from the mucosal aspect and invaded through the detrusor muscle to invade the perivesical fat and the serosa [ figure 3 ] . the tumor cells were seen extending along the adventitia of both the ureters even up to the surgical cut margins . on immunohistochemistry the tumor cells were positive for ck , ck 7 [ figure 4 ] and cd 138 ; while they were negative for lca , cd20 , and light chains . plasmacytoid urothelial carcinoma : the tumor cells are seen undermining the normal urothelium with retraction spaces around them . immunohistochemical staining with antibody to ck7 marks the tumor cells as well the overlying urothelium thereby confirming their epithelial origin . the patient is on regular follow - up and is doing fine for last 6 months without any evidence of recurrence or metastasis elsewhere in the body . recent years have witnessed the illustrations and documentation of several morphological variants of urothelial carcinomas , which have significance from therapeutic and prognostic perspective . the plasmacytoid variant is an unusual variant that has been recognized in the latest who classification of urothelial carcinomas . earliest description of this variant came from the case reported by sahin et al , in 1991 and since then , not more than 40 cases have been reported,[26 ] there is very limited data available about the pathological , immunohistochemical characteristic as well as clinical behavior of this rare variant . most common presenting symptom is hematuria.[48 ] histopathologically , plasmacytoid urothelial carcinoma is characterized by plasmacytoid tumor cells arranged in cords and single - file pattern , small nests , solid sheet like growth or diffuse discohesive pattern - less architecture . the nuclei vary from hyperchromatic to vesicular with evenly distributed chromatin and variability in the prominence of nucleoli . prominent retraction artifact around each tumor cell may also be seen . in the present case the plasmacytoid urothelial carcinoma can coexist with non - invasive papillary urothelial carcinoma , urothelial carcinoma in situ or invasive high - grade urothelial carcinoma . however , in our case there were no areas of either papillary or in situ urothelial malignancy . plasmacytoid appearance of this tumor can lead to diagnostic dilemma , especially in smaller biopsies . differential diagnosis ranges from benign conditions like chronic cystitis with prominent plasma cell infiltrate to malignant tumors like plasmacytoma and signet ring carcinoma . in our case some cells also had focal signet ring - like appearance which led to confusion with signet ring cell carcinoma . however , the nuclei were eccentric rather then being peripherally compressed as in true signet ring cell carcinoma . metastatic carcinoma from breast or stomach , malignant melanoma and rhabdomyosarcoma can have striking plasmacytoid morphology and can cause considerable diagnostic difficulties . in such situations , it is imperative to employ a panel of antibodies for confirmation of diagnosis . immunohistochemical studies have shown that plasmacytoid urothelial carcinoma cells to be positive for ck-7 , ck-20 , ck , ae1/ae3 , ema and cd-138 , but negative for lca , s 100 , hmb 45 , , and cd 79- , as was seen in our case also . because of late presentation , biopsy usually reveals a high - grade tumor infiltrating the lamina propria and muscularis , with high potential of metastasis . some reports have shown good response to neoadjuvant chemotherapy , but this aspect needs further evaluation . our patient also had high - stage disease ( pt3 ) and underwent radical cystectomy with ileal conduit . on final histopathology , the tumor cells were seen extending along the ureteric adventitia till the surgical resection margins . prognosis is extremely poor with an aggressive behavior of this variant . in the case series by nigwekar et al , no patient with greater than 1-year another report by lopez - beltran et al , showed that within 2 years of follow - up , all patients either died of cancer or had metastasis . in our case the patient is free of disease since last 6 months after surgery . in conclusion , plasmacytoid variant of urothelial carcinoma is a rare and important variant form diagnostic , therapeutic and prognostic point of view . it can be mistaken for other pathologies of bladder having plasmacytoid features and should be differentiated from them because of the difference in the therapeutic approach .

plasmacytoid urothelial carcinoma is an uncommon and aggressive variant of urothelial carcinoma associated with late presentation and poor prognosis . we discuss here the first reported case from india of a 54-year - old male who presented with hematuria . cystoscopy showed edematous and ulcerated mucosa throughout the bladder . a transurethral biopsy revealed urothelial carcinoma with plasmacytoid appearance . he underwent a radial cystectomy which on histopathology showed plasmacytoid urothelial carcinoma of the bladder of high stage with involvement up to bladder serosa and adventitial walls of the ureter . the diagnostic dilemmas of this unusual variant of urothelial malignancy and its clinical impact are discussed .

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abstractanalytical methods that enable visualization of nanomaterials derived from solution selfassembly processes in organic solvents are highly desirable . herein , we demonstrate the use of stimulated emission depletion microscopy ( sted ) and single molecule localization microscopy ( smlm ) to map living crystallizationdriven block copolymer ( bcp ) selfassembly in organic media at the subdiffraction scale . four different dyes were successfully used for singlecolour superresolution imaging of the bcp nanostructures allowing micelle length distributions to be determined in situ . dualcolour smlm imaging was used to measure and compare the rate of addition of red fluorescent bcp to the termini of green fluorescent seed micelles to generate block comicelles . although wellestablished for aqueous systems , the results highlight the potential of superresolution microscopy techniques for the interrogation of selfassembly processes in organic media .

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first generation antipsychotics along with amisulpride , risperidone , paliperidone , and zotepine have been consistently reported to be associated with the high rates of hyperprolactinemia and termed as prolactin - raising , whereas clozapine , olanzapine , quetiapine , ziprasidone , and aripiprazole , which have a more favorable profile , have been termed as prolactin - sparing . switching over to aripiprazole or adjunctive aripiprazole , has been advocated for the optimal management of antipsychotic - induced hyperprolactinemia . adjunctive treatment with aripiprazole has been shown to normalize prolactin levels without affecting improvements in the psychotic symptoms that had already been achieved with the previous antipsychotic treatment . however , a literature search shows the case reports of paradoxical hyperprolactinemic symptoms such as galactorrhea associated with aripiprazole use . saraf et al . in a case report of a female , who developed hyperprolactinemia , while on aripiprazole , postulated that aripiprazole could have dopamine antagonistic properties at higher doses as the partial d2 agonistic activity could be dose - related . recent research has also shown that the beneficial effect of aripiprazole on other antipsychotic - induced hyperprolactinemia is seen at lower doses and plateaus off at higher doses . however , here , we present the case of a female with the delusional disorder who developed symptomatic hyperprolactinemia even while on a low dose ( 10 mg / day ) of aripiprazole . a 36-year - old married female was presented to the psychiatry outpatient services with 2 years of delusion of infidelity and significant sociooccupational dysfunction in the absence of any impairment in sleep or appetite . vitals were stable , body mass index ( bmi ) was calculated to be 26 and systemic examinations revealed no abnormality . baseline prolactin level was 14 ng / ml . in view of the high bmi and poor insight , she was started on aripiprazole . it was expected that the favorable side effect profile of aripiprazole with relatively less weight gain and extrapyramidal symptoms would ensure compliance . aripiprazole was started at an initial dose of 5 mg at night and was increased to 10 mg and later 15 mg after 4 days each and 15 mg was continued as maintenance . however , 3 weeks later , she was presented with galactorrhea and a missed menstrual period . the possibility of aripiprazole - induced hyperprolactinemia was considered and aripiprazole was stopped . as she was otherwise asymptomatic , no other medication was started and she was sent home . at follow - up , 1-month later , galactorrhea had subsided , she had menstruated , and repeat prolactin levels were 18 ng / ml . her psychotic symptoms continued to be in remission , and she returned home medication - free . aripiprazole was restarted as previously , but was maintained at 10 mg owing to the previous history of hyperprolactinemia . she reported back within a month with the complaints of galactorrhea and amenorrhea at which time her psychotic symptoms were in complete remission . serum prolactin levels were repeated and found to be elevated ( 84 ng / ml ) . serum prolactin levels were normalized ( 19 ng / ml ) and hyperprolactinemia symptoms were subsided within 1-month . peptides , steroids , and neurotransmitters regulate the synthesis and release of the hormone prolactin from the lactotrophs of the anterior pituitary . dopamine acts as a tonic inhibitor of prolactin secretion through the tuberoinfundibular and the tuberohypophysial dopaminergic systems . the binding of dopamine to the d2 receptors on the membrane of the lactotroph cells inhibits the prolactin gene transcription , synthesis and release of prolactin , and lactotroph proliferation . on the other hand , d2 receptor blockade by antipsychotics counteracts the tonic inhibitory effect of dopamine on prolactin secretion , thus elevating serum prolactin levels . the degree of hyperprolactinemia caused correlates with the penetrability of the blood - brain barrier and the strength of the dopamine blockade . the quicker the drug dissociation from the receptor , the lesser is the increase in plasma prolactin . the functional activity of a partial agonist at the specific receptor depends on the presence or absence of other full agonists and antagonists in the surrounding milieu . they bind to the receptor to produce the physiological response seen , when the receptor is activated . however , if a full agonist is simultaneously present , the partial agonist shows functional antagonist activity . it competes with the full agonist for receptor occupancy and when bound , the response is lesser than that seen with the full agonist alone . aripiprazole has a lower intrinsic activity at the d2 receptor than dopamine , allowing it to act as both , a functional agonist and antagonist , depending on the surrounding levels of dopamine . in the presence of a prolactin - raising antipsychotic , adjunctive aripiprazole competes with it to possibly act as an agonist in the tuberoinfundibular pathway , thus bringing down the elevated prolactin levels . however , as a stand - alone treatment , the functional activity of aripiprazole in this pathway would be dependent solely on the dopamine levels . hence , it is possible that in the absence of a competing d2 antagonist and the presence of dopamine ( the natural agonist ) , aripiprazole could act as a functional antagonist at lower doses also , and thus , elevate prolactin levels .

hyperprolactinemia is a common adverse effect of antipsychotic medication . switching over to aripiprazole or adjunctive aripiprazole has been advocated for optimal management of antipsychotic - induced hyperprolactinemia . adjunctive treatment with aripiprazole has been shown to normalize prolactin levels without affecting already achieved improvements in psychotic symptoms . however , here , we present the case of a 36 year old female with delusional disorder who developed symptomatic hyperprolactinemia while on aripiprazole treatment . dopamine acts as a tonic inhibitor of prolactin secretion through the tubero - infundibular dopaminergic system . aripiprazole being a partial agonist has a lower intrinsic activity at the d2 receptor than dopamine , allowing it to act as both , a functional agonist and antagonist , depending on the surrounding levels of dopamine . hence , in the absence of a competing d2 antagonist and the presence of dopamine ( the natural agonist ) , aripiprazole could act as a functional antagonist and thus elevate prolactin levels .

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this study was conducted in accordance with a protocol approved by an institutional animal care and use committee of the national institutes of health . all laboratory work with potentially infectious materials was conducted in a biosafety level facility at the rocky mountain laboratories ( division of intramural research / national institute of allergy and infectious diseases / national institutes of health ) . three cynomologus macaques were vaccinated with 1 dose of 10 pfu of vsvg / lasvgpc , a live - attenuated , recombinant viral vaccine in which the vsv surface glycoprotein has been replaced with those of lasv , by intramuscular injection as described ( 4 ) . another age - matched control animal was vaccinated with an irrelevant vsv - based vaccine ( vsvg / andvgpc ) ( 5 ) . at 28 days postvaccination , the 4 nhps were challenged with a lethal dose of lasv ( 10 50% tissue culture infectious doses [ tcid50s ] ) ( 9 ) . the control animal showed signs of lassa fever 710 days postinoculation and was euthanized 13 days postchallenge because of severity of disease . classic indicators of lassa fever , including decreased total protein and albumin ; increased serum levels of alanine aminotransferase , aspartate aminotransferase , amylase , blood urea nitrogen , and alkaline phosphatase ; and hematologic abnormalities , including thrombocytopenia and lymphopenia , were apparent in this animal . virus isolation conducted for select tissue samples showed lasv titers of 57 log10 tcid50/g of tissue ; blood samples collected on day 10 and at the time of euthanasia ( 5 and 6.25 log10 tcid50/ml , respectively ) showed viremia . in contrast , the 3 animals vaccinated with vsvg / lasvgpc resisted lethal lasv challenge and did not demonstrate any clinical signs of disease or any hematologic or biochemical indicators of lasv infection . at no point in the study was virus found in blood samples collected regularly from these 3 animals , even when tested by sensitive reverse transcription pcrs . an elisa with serum samples collected 45 days postchallenge demonstrated equivocal antibody titers ( 100 ) against a recombinant lasv nucleocapsid protein in 1 nhp . the other 2 animals did not show seroconversion , which suggested that vaccination caused nearly sterile immunity against lasv ( table ) . * vsv , vesicular stomatitis virus ; vhf , viral hemorrhagic fever ; lasv , lassa virus ; gpc , glycoprotein precursor ; np , nucleocapsid protein ; ebov , ebola virus ; gp , glycoprotein ; vp40 viral protein 40 ; nd , not determined . titers are indicated as reciprocal endpoint dilutions from elisas for recombinant antigens ( lasv np , ebov gp , and vp40 ) , or whole virus preparations ( vsv ) . approximately 90 days after the original vaccination with vsvg / lasvgpc , the 3 nhps were vaccinated with a single dose of 10 pfu of vsvg / ebovgp by intramuscular injection as described ( 3 ) . an additional nhp was vaccinated with a control vaccine as outlined above and served as the inoculation control . at the time of vaccination , the 3 macaques had a robust vsv - specific antibody response with titers of 25,600 , as determined by a whole virus elisa ( table ) . despite this finding , the 3 animals that received the vsv - based ebov vaccine mounted an efficient response to the ebov glycoprotein ( table ) and were completely protected when challenged 28 days later with a lethal dose of ebov ( 10 pfu ) ( 10 ) . hematologic and serum biochemistry values remained constant throughout the study , and virus was not found in blood samples collected regularly and tested by using real - time reverse transcription pcr . in contrast , severe ebov hemorrhagic fever developed in the control animal , which was characterized by increased serum concentrations of alkaline phosphatase , aspartate aminotransferase and alanine aminotransferase ; thrombocytopenia ; and viremia ( 7 log10 tcid50/ml whole blood ) beginning 36 days postchallenge . this animal was euthanized 7 days postchallenge , and titration of selected tissue samples showed ebov titers of > 9 log10 tcid50/g tissue . an elisa conducted at the conclusion of the study ( 42 days post ebov challenge ) showed increased antibody responses to vsv ( titers = 102,400 ) and seroconversion to the ebov viral protein 40 antigen ( titers 1,6006,400 ) in the 3 surviving nhps ( table ) , which is consistent with published results ( 10 ) . because of the remote locations where vhf agents are present , an overall shortage of health care professionals and clinics in these locations , and mobility of human populations , any vaccine against these pathogens would ideally need to elicit a protective immune response after a single vaccination . for this reason , replication - competent viral vectors are considered leading vhf vaccine candidates . as the vsvg / ebovgp vaccine heads toward clinical trials , it is necessary to clarify the potential limitations of using the vsv platform against multiple vhf agents . a major drawback for many viral vector platforms is preexisting immunity against the vector itself , which can decrease or nullify the essential protective immune response , which results in vaccine failure . design of the vsv - based vaccines , which encode and express glycoproteins from various pathogens without its own glycoprotein ( 11,12 ) , suggest that preexisting immunity would not influence protective efficacy of individual vaccinations ( 12 ) . results of this study demonstrate that multiple vsv vaccines can be used in a population without any deleterious effect on overall protective efficacy .

we demonstrated that previous vaccination with a vesicular stomatitis virus ( vsv)based lassa virus vaccine does not alter protective efficacy of subsequent vaccination with a vsv - based ebola virus vaccine . these findings demonstrate the utility of vsv - based vaccines against divergent viral pathogens , even when preexisting immunity to the vaccine vector is present .

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currently , complete surgical resection represents the only curative treatment for lung cancer1 . however , the majority of lung cancer survivors who undergo lung resection experience pulmonary complications ; one - third of these patients report dyspnea , and one - fifth suffer from severely diminished pulmonary function , including respiratory muscle weakness2 . pulmonary rehabilitation ( pr ) has been proposed as an adjunctive therapy to decrease the risk of postoperative pulmonary complications3 . however , patients may not be able to consistently engage in pr , for personal or economic reasons ( e.g. , lacking the funds to travel to rehabilitation centers)4 . therefore , there is a need for alternative methods , such as home - based pr , to maintain physical functioning in a more economical manner5 . few studies have addressed pr education for caregivers , who typically facilitate home - based exercises during the outpatient period . this study evaluated the effects of caregiver education on pr ( i.e. , respiratory muscle strength and dyspnea ) in lung cancer patients following lung resection . patients scheduled for lung resection at the department of thoracic surgery of a national university hospital , between march 2013 and november 2013 , whose caregivers had not previously received education pertaining to pr , were selected for the study . a total of 50 patients agreed to participate following an explanation of the study procedure , and written informed consent was obtained from all participants . ethics approval was obtained from the inje university faculty of health science human ethics committee . the subjects were randomly assigned to experimental ( n = 25 ) and control ( n = 25 ) groups the day before surgery . of these , 3 and 6 subjects dropped out of the experimental and control groups , respectively , during the 4-week study period , due to violation of the exclusion criteria . therefore , the final experimental and control groups were comprised of 22 and 19 subjects , respectively . the subjects mean age was 60.2210.89 years ; their mean height was 163.01 8.77 cm , mean weight was 61.3911.35 kg , and average bmi was 23.013.34 . caregiver education on pr included guidance pertaining to splinted coughing , airway clearance and breathing , and stretching and strengthening exercises . the control group received general advice from the department of thoracic surgery ( once per week for 30 minutes ) pertaining to pain management , postoperative care , use of an incentive spirometer and nebulizer , and mobilization of the upper limbs and trunk . in the case of subjects who were not able to visit the hospital , respiratory muscle strength was assessed using a microrpm device ( micro medical ltd . , maximum expiratory pressure ( mep ) were measured using the method described by black & hyatt6 , and these served as indices of inspiratory and expiratory muscle strength . dyspnea was evaluated using the modified borg scale , ranging between 0 ( no dyspnea ) and 10 ( most severe dyspnea ) . data pertaining to the general characteristics of subjects are provided as means se , with intergroup homogeneity assessed using and independent t - tests . group differences in scores before the experiment , and 2 weeks ( baseline ) and 6 weeks after surgery , were assessed using repeated - measures analysis of variance . mip , mep and modified borg scale values were more significantly improved in the experimental group compared to the control group , but there were no group differences ( p<0.05 , table 1table 1.comparison of respiratory muscle strength and dyspneamean sdcontrolexperimentalmip ( cmh2o)baseline62.521.463.818.24 weeks68.021.271.519.0*mep ( cmh2o)baseline62.4224.361.615.64 weeks66.532.571.216.8*mborgbaseline3.081.162.451.464 weeks2.631.611.771.40**p<0.05 ) . refai et al.7 reported an association between respiratory muscle weakness after lung resection and increased incidence of pulmonary complications . recovery of respiratory muscle function after surgery is important because lung resection leads to impairments in these muscles . nomori et al.8 reported a 4.3% increase in mip , and 6.4% increase in mep , 212 weeks after surgery . these data are consistent with our finding that mip and mep increased between weeks 26 in the control ( 8% and 6% , respectively ) and experimental ( 12% and 15% , respectively ) groups . however , these group differences were not significant . previous studies demonstrated that smaller lung resection areas are associated with greater differences in respiratory muscle strength before and after surgery8 , 9 . we speculate that respiratory muscle strength did not differ significantly among our groups because all subjects had undergone video - assisted thoracoscopic surgery , which requires a minimal incision in the respiratory muscles interacting with the chest wall . dyspnea caused by lung resection is an important determinant of patients quality of life10 . our study commenced 2 weeks after the surgery ; the experimental group was characterized by a decrease in dyspnea over time , but this decrease was not significant compared to the control group . differences between our results and those of this previous study may be due to the use of indirect and direct interventions , respectively . in conclusion , our data suggest that caregiver education on pr can improve respiratory muscle strength and dyspnea .

[ purpose ] this study evaluated the effects of caregiver education on pulmonary rehabilitation of patients who have undergone lung resection for cancer . [ subjects ] patients were divided into experimental ( n = 22 ) and control ( n = 19 ) groups . [ methods ] the caregivers of the experimental group patients received education on pulmonary rehabilitation , while the control group patients received general management advice for 4 weeks . [ results ] pulmonary muscle strength ( maximum inspiratory pressure and maximum expiratory pressure ) was increased significantly in the experimental group compared to the control group . modified borg scale scores were decreased significantly in the experimental vs. control group . [ conclusion ] providing caregivers with education pertaining to pulmonary rehabilitation was associated with improved pulmonary function in lung cancer patients following lung resection .

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there is an increasing concern amongst the women and girls about the appearance of their external genitalia . many women and adolescent girls present with labia hypertrophy . a young girl presenting with labia hypertrophy is quite unusual . a child with severe hypertrophy of bilateral labia minora patient a , youngest of six female siblings , was born at term in a hospital through the lower segment caesarean section . at 8 years of age , she noticed progressive increasing size of labia , which caused her pain while prolonged sitting , walking and daily activities . the increased size of labia affected her psychologically as she considered herself abnormal among her siblings . she disclosed the enlargement to her elder sister almost after 6 months of noticing it , and the patient consulted the plastic surgery clinic at the age of 8 years . on clinical examination , her labia minora was found to be thickened and enlarged more than 5.5 cm from the free edge of the labia majora with associated hypertrophy of the clitoral hood [ figures 1 and 2 ] ( type 6 : franco 's classification ; severe hypertrophy : ricci and pardo classificatio ) [ tables 1 and 2 ] . pre - operative view of labia minora hypertrophy size of labia minora measuring 5.5 cm in its width franco classification of labia minora hypertrophy ricci and pardo classification of labia minora hypertrophy for surgical correction on work - up , her hormonal assay revealed no abnormality . her thyroid profile , serum luteinizing hormone , serum follicle - stimulating hormone , serum testosterone and serum estradiol levels were within normal limits . skin and subcutaneous tissues in the labia minora were found to be hyperplastic . extended linear excision was performed which included excision of hypertrophied clitoral hood [ figures 3 and 4 ] . after 24 h , the patient was advised to clean the genitalia with application of antiseptic ointment . linear excision of labia minora and clitoral hood reduction immediate post - operative result ( a and b ) post - operative result after two weeks with good aesthetic appearance histological examination showed acanthosis and chronic non - specific inflammation of underlying dermis [ figure 6a and b ] . ( a and b ) histological picture illustrating mild acanthosis with mild chronic non - specific inflammation with congestion ( 40 , h and e ) hodgkinson and hait first described labia minora hypertrophy in 1984 ; though description regarding circumcision of labia minora and clitoris has been mentioned vaguely in many old scriptures . juvenile labia minora hypertrophy [ jlmh ] is a less common clinical condition and becomes rarer in a developing country like india where social taboos and customs are stringently enforced in the common lives . in such milieu , jlmh cases are detected only when symptoms significantly affect a patient 's functional and psychological well - being . hence , whenever a surgeon in a developing country like india diagnoses a jlhm patient , it should be addressed properly , and relevant procedure should be carried out to relieve the patient from distressing symptoms . although no standard consensus has been established yet to classify labia minora hypertrophy ; many do exist depending on the size and severity of the hypertrophy [ tables 1 and 2 ] . arbitrary landmarks taken in these measurements make it difficult to diagnose hypertrophy on a standard scale . some have measured size from midline horizontally , and some have measured from free edge . . surgical decision should largely be dependant on labia size as well as symptoms addressed by the patient . a number of studies have been published in context to labia minora hypertrophy and their management , but only a few have addressed the occurrence of hypertrophy in adolescent age and most of their patients fall in 2040 age group . although age is not a criterion for labiaplasty , most of the surgeons refrain from doing it at an early age . our patient was an 8-year - old when she noticed labial hypertrophy , which is rare . all the relevant investigations , including hormonal assays and usg were normal suggestive of an idiopathic , isolated and abnormal morphology of the labia . the size of the labia minora as well as presenting symptoms should be taken into account , while planning labiaplasty in any age group , especially in adolescents . a better classification system for labia minora hypertrophy and standardization regarding functional and cosmetic labiaplasty need to be established in this era of ever increasing vulvovaginal surgeries .

labia minora hypertrophy is a relatively uncommon surgical entity being popularised in the realm of vulvovaginal plastic surgeries . apart from the unaesthetic appearance of the hypertrophied minora , these cases are also associated with itching , hygiene problem , pain while sitting down , sports activities , difficulty in wearing tight clothing , bleeding and discomfort while or after sexual intercourse , social embarrassment , insecurity and psychological diminution of confidence and self - esteem . in a country like india , due to sociocultural reasons , patients hesitate to consult a doctor for such deformities . most of the patients suffer in silence for years . although common in the west , very few surgeons in the country perform this simple and rewarding surgery . here , we are presenting a case of premenarchal juvenile labia minora hypertrophy ( jlmh ) in an 8-year - old child . labial hypertrophy in this age group is uncommon . we were unable to find hypertrophy of labia minora in the eight - year - old child on english literature search .

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both interstitial granulomatous dermatitis ( igd ) and palisaded neutrophilic granulomatous dermatitis ( pngd ) are rare disorders typically associated with systemic autoimmune conditions . they probably represent different aspects of a disease spectrum encompassing the concept of autoimmunity - related granulomatous dermatitis ( argd ) . the present case shows that the clinicopathological correlation in argd does not always clearly fit with the classical presentations of igd or pngd . a number of autoimmune conditions are associated with cutaneous symptoms . interstitial granulomatous dermatitis ( igd ) the typical clinical presentation corresponds to a linear rope present on the trunk and axillae . on histopathological examination , igd is characterized by a sparse palisaded histiocytic infiltrate with little neutrophilic debris and eosinophils associated with a necrobiotic aspect of the collagen matrix . in the literature , there is some overlap between igd and palisaded neutrophilic granulomatous dermatitis ( pngd ) . lesions of pngd typically correspond to papules occasionally admixed with small crusts on the elbows . other related disorders include rheumatoid papules , churg - strauss granuloma , superficial ulcerating rheumatoid necrobiosis , necrobiotic granuloma , palisading granuloma , cutaneous extravascular necrotizing granuloma , and rheumatoid neutrophilic dermatitis . here , a 61-year - old woman presented with skin lesions over the elbows and the left thenar region . they corresponded to erythematous and discrete hyperkeratotic papules which had been present for a few weeks ( fig . immunohistochemistry revealed the presence of cd3 + t lymphocytes predominating in the perivascular area ( fig . they were associated with cd68 + and mac387 + histiocytes as well as factor xiiia+ dermal dendrocytes ( dd1 ) . the pattern of dd1 distribution was similar to that of cd68 + histiocytes ( fig . it was characterized by the elevation of anti - smooth muscle antibodies ( 1:160 ) and antinuclear antibodies ( 1:1,280 ) . there were no detectable antibodies directed against nuclear antigens , keyhole limpet hemocyanin and mitochondria . hepatitis b and c serologies were negative . at the time of presentation , the patient 's liver tests were in the normal range . however , they recurred a few months later , and some other lesions appeared on the thighs . in some cases , there is a mismatch between the clinical presentation and the histopathological patterns of igd and pngd . indeed , these two conditions possibly represent a continuum or progression of a single disease process corresponding to autoimmunity - related granulomatous dermatitis ( argd ) [ 6 , 8 ] . the clinical associations between argd , autoimmune disease and lymphoproliferative disorders have been intermixed between both igd and pngd diagnoses in the literature [ 6 , 9 , 10 , 11 , 12 , 13 , 14 ] . it is acknowledged that the inflammatory cell infiltrate is sparse to moderate in igd , while pngd has a dense neutrophilic and interstitial histiocytic infiltrate . only a single case of igd with autoimmune hepatitis association has been reported so far . some other autoimmune comorbidities including arthritis , antiphospholipid syndrome [ 18 , 19 ] and hematologic malignancy have been reported in association with igd . in addition , interstitial granulomatous drug reactions have been linked to tnf inhibitors , ace inhibitors , diuretics [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ] and soy products in food .

aimboth interstitial granulomatous dermatitis ( igd ) and palisaded neutrophilic granulomatous dermatitis ( pngd ) are rare disorders typically associated with systemic autoimmune conditions . they probably represent different aspects of a disease spectrum encompassing the concept of autoimmunity - related granulomatous dermatitis ( argd).case reporta 61-year - old woman presented with argd and autoimmune hepatitis . the clinical presentation suggested pngd , while histopathology was consistent with igd.discussionthe association of argd with autoimmune hepatitis is apparently a rare event . the present case shows that the clinicopathological correlation in argd does not always clearly fit with the classical presentations of igd or pngd .

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abnormal variation of the posterior corneal curvature may occur in two forms : the generalized posterior keratoconus , characterized by an regular increase of the curvature of the entire posterior corneal surface has , and the circumscribed posterior keratoconus , in which a localized paracentral or central posterior corneal indentation is seen . in the generalized form , the corneal stroma typically remains clear . in contrast , the circumscribed posterior keratoconus shows stromal opacities overlying the localized anterior ectasia of the posterior surface , which may occupy the full stromal thickness . circumscribed posterior keratoconus is usually bilateral and sporadic , but familial cases have been also documented . despite the anterior protrusion in some cases , the 60-year - old white male of mediterranean origin presented for a cataract extraction on his left eye . visual acuity was 20/25 in the right eye and light perception in the left eye due to cataract formation . the patient denied history of injury , reporting only a bilateral ocular infection in childhood was reported . slitlamp examination revealed a bilateral paracentrally localized depression of the posterior curvature measuring 3 mm in diameter . there was scarring in the overlying corneal stroma ( figures 1 , 2 , and 3 ) . the posterior depression was clearly detectable using ultrasound biomicroscopy ( humphrey , zeiss , oberkochen ) ( figure 5 ) and slit - scanning topography analysis ( orbscan , bausch and lomb ) ( figure 6 ) . corneal thickness measured 450 m within the lesion and 540 m in the adjacent healthy cornea using the orbscan system . the refractive power of both the posterior and anterior corneal curvature was 50 to 56 diopters within the paracentral area . following phacoemulsification and posterior chamber lens implantation visual acuity increased to 20/50 in the left eye . the clinical and topographic findings in this patient are consistent with the paracentral keratoconus posterior circumscriptus . this is the first report on ultrasound biomicroscopy to visualise the local anterior bulging of the posterior corneal surface with concomitant thinning of the stroma . light microscopy of this abnormality has shown focal disorganization of basal epithelium and basement membrane , a replacement of bowman 's layer by fibrous tissue , a thinned stroma with an irregular arrangement of the central collagen lamellae , and a variable appearance of descemet 's membrane with posterior excrescences indentating the vacuolated endothelium correspond to the corneal guttae seen in specular reflection . iron deposits are present in the basal and suprabasal epithelium , corresponding to the brownish epithelial line observed clinically , indicating an irregularity of the anterior corneal surface . visualisation of the posterior keratoconus using corneal topography analysis has been reported so far in a few cases [ 7 , 8 ] . the light microscopy findings suggest an early pathogenic mechanism probably originated in the fifth or sixth month of gestation . it is classified as one of the anterior chamber cleavage anomalies ( mesenchymal dysgenesis ) , as there are other anterior segment and systemic developmental abnormalities , as well as melanin depositions surrounding the posterior depression and iridocorneal adhesions . however , not all cases share this phenomenon . acquired cases occur and are usually associated with trauma [ 9 , 10 ] . the mechanism in such cases involves an oblique penetrating injury with splitting of the inner corneal layers . differential diagnosis also includes congenital disorders as peter 's anomaly and congenital hereditary endothelial dystrophy but they are usually found in new borns . inflammation process as perforated corneal ulcer may also be taken into consideration , but it is usually unilateral . in most of the cases of posterior keratoconus the vision is not affected , rarely it may be associated with other ocular abnormalities as polar cataract , lenticonus , and ectopia lentis .

this paper documents a rare nonprogressive developmental disorder bilateral circumscribed posterior keratoconus in a 60-year - old man referred for a cataract surgery . for the first time ultrasound biomicroscopy was used to visualise the local anterior bulging of the posterior corneal surface with concomitant thinning of the stroma . the amount of localized posterior depression , corneal thickness and the refractive power of both the posterior and anterior corneal curvature were measured using slit - scanning topography analysis ( orbscan ) .

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we report the case of a 58-year - old woman with intracranial hemorrhage associated with stress - induced cardiomyopathy . left ventricular dysfunction was confined to midventricular segments , and manifested with transient anterolateral wall aneurysm . although wall motion was severely impaired in the mid - segments , an almost preserved global midventricular radial strain forecasted rapid improvement of ventricular function . this case highlights how deformation imaging can help in clinical practice to interpret the subtle signs of recovery from left ventricular dysfunction . a 58-year - old woman was admitted one year ago to the neurointensive care unit of our hospital for sudden onset of intracerebral and subarachnoid hemorrhage of the right frontal lobe . she had a history of tobacco use and moderate alcohol abuse , hypertension and chronic obstructive pulmonary disease . her surgical history included left lumpectomy for breast cancer , amputation of the third finger on the right hand and jaw surgery a few years ago . at admission her vital signs were within the normal range : blood pressure 140/87 mmhg , heart rate 71 beats per minute ( bpm ) , respiratory rate 20 breaths per minute and oxygen saturation on ventilator 100% . the electrocardiogram ( ecg ) at admission showed normal sinus rhythm ( 60 bpm ) and possible septal necrosis . right craniotomy for evacuation of the hemorrhage and clipping of right middle cerebral artery aneurysm were performed . troponin i levels showed a slight increase from 0.33 to 3.55 ng / ml during the first two days , and then decreased to 1.96 ng / ml on the third day postsurgery , and similar variations were seen for the levels of creatine kinase - mb fraction ( from 4.0 to 11.5 to 4.3 ecg on the second day showed deep negative t waves in almost all leads with prolonged qtc interval [ figure 1 ] . due to abnormal myocardial necrosis markers and ecg , a two - dimensional ( 2d ) transthoracic echocardiogram was ordered , and revealed a normal left ventricular cavity size with hyperdynamic basal motion , akinesis of midventricular segments and nearly normal apical motion [ figure 2 ] . left ventricular global systolic function was moderately decreased with left ventricular ejection fraction at 35% ( normal values > 55% ) . electrocardiogram on second day post - right craniotomy for evacuation of hemorrhage and clipping of right middle cerebral artery aneurysm showing deep negative t waves in almost all leads with prolonged qtc interval ( 580 ms ) two - dimensional transthoracic echocardiography in the apical four - chamber view showing the left ventricle a ) at end diastole and b ) mid - systole . basal and apical segments contract well in contrast to midventricular segments the next day , the patient underwent coronary angiography , which ruled out any coronary artery disease . however , the ventriculogram surprisingly revealed an aneurysmatic anterior wall [ figure 3 ] , which then was characterized by another transthoracic echocardiogram as an anteroseptal wall aneurysm with near - normal motion of the other segments [ figure 4 ] . global radial strain was calculated and , despite seriously compromised midventricular anteroseptal motion , midventricular - averaged radial strain was at the lower end of normal range ( i.e. 16% ) . left ventriculogram showing systolic anterior wall aneurysm two - dimensional transthoracic echocardiography in the apical long - axis view showing anteroseptal wall aneurysm with nearly normal motion of the other segments in a ) end diastole and b ) mid - systole as predicted by the global radial strain in the previous examination , another transthoracic echocardiogram performed three weeks later documented the complete resolution of wall motion abnormalities [ figure 5a and b ] , with completely normal radial strain values [ figure 5c ] . two - dimensional ( 2d ) transthoracic echocardiogram in the apical long - axis view showing complete resolution of wall motion abnormalities at a ) end diastole and b ) mid - systole . on the left , a short - axis view of the mid - left ventricle is shown , and a 2d speckle tracking technique is used to obtain the curves representing radial deformation of each wall segment ( right ) . the averaged global strain is 57% ( represented by white curve ) isolated left ventricular midventricular dyskinesia is a rare variant of stress - induced cardiomyopathy , although it has been described in association with cerebral injuries . left ventricular mechanics in stress - induced cardiomyopathy have not been well defined , although some data about the longitudinal and radial strain are available . our case highlights the importance of global radial strain as a predictor of myocardial wall motion improvement , even when 2d transthoracic echocardiogram did not forecast the improvement .

introduction : we report the case of a 58-year - old woman with intracranial hemorrhage associated with stress - induced cardiomyopathy.results:left ventricular dysfunction was confined to midventricular segments , and manifested with transient anterolateral wall aneurysm . although wall motion was severely impaired in the mid - segments , an almost preserved global midventricular radial strain forecasted rapid improvement of ventricular function.conclusions:this case highlights how deformation imaging can help in clinical practice to interpret the subtle signs of recovery from left ventricular dysfunction .

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a 67-year - old male patient had undergone esophagectomy and intrathoracic esophagogastrostomy for carcinoma of the lower thoracic esophagus 27 months earlier . the original pathologic condition was determined to be moderately differentiated squamous cell carcinoma invading the lamina propria without lymph node metastasis ( clinical t1bn0m0 ) . he had undergone follow - up chest computed tomograph and esophagogastroduodenoscopy once or twice a year and a gastric carcinoma at the intra - abdominal part of the gastric conduit was found . the tumor was a 2a+2c type lesion and located in the posterior wall of the antrum . because of its morphology ( flat and depressed type with ulceration ) , size ( more than 10 mm ) and poor localization , endoscopic mucosal resection or partial gastric resection was not suitable ( fig . 1 ) , so we decided to perform a total resection of the gastric conduit . the whole procedures were performed in 3 stages : first thoracic , second abdominal , and third thoracic and abdominal approaches . because of previous intrathoracic esophagogastrostomy , it was necessary to check the intrathoracic condition and operability . the esophago - gastric anastomosis was located at the upper part of the paratracheal area ( figs . 2 , 3 ) . after dissecting the adhesions between the pleura , lung , and gastric conduit with blunt and sharp procedures , we resected the gastric conduit at the level of the previous anastomosis . the intrathoracic portion of the esophagus was about 4 cm segment long , so we saved it as long as possible and inserted the 28 mm anvil into it . the antral portion of the stomach was adhered to the diaphragm , liver , and surrounding structures . the length and vasculatures of the transverse and descending colon were considered to be suitable for an esophageal conduit . the left side of the colon with a pedicle of the left colic artery was prepared for esophageal reconstruction . the proximal sigmoid colon was connected ( end to side ) to the proximal part of the transverse colon with a 28 mm end - to - end anastomosis ( eea ) stapler . after the left - sided colon conduit into the thoracic cavity in the isoperistaltic manner , esophago - colonostomy was done with a 28 mm eea stapler . the distal part of the colon conduit was anastomosed at the side of the proximal jejunum with a 25 mm stapler in the manner of roux - en - y anastomosis . on the 10th postoperative day , an esophagogram showed no leakage or stenosis of the passage ( fig . the patient has received follow - up care for 7 months after surgery without any problems . after warren and gates reported on it in 1932 , the concept of multiple primary malignancies has been accepted widely and is supported by hypothesis of field cancerization . synchronous or metachronous multiple primary malignancies in esophageal cancer have since been reported with a frequency of about 10% . gastric conduit cancer is not only cancer arising in the remnant gastric conduit but also the second primary cancer following esophageal cancer . the incidence of gastric conduit cancer has been reported to be 0.2%-3.5% [ 2 - 4 ] . although the etiology of the secondary carcinoma in the gastric conduit is not well known , gastric conduit cancer has been reported increasingly because of survival prolongation of esophageal cancer patients after surgery . in our hospital , we have annually operated on about 30 esophageal cancer patients with gastric conduit and this surgical management of gastric conduit cancer was our first experience . because thoracotomy with adhesiolysis is necessary for performing a reoperation , total resection of the gastric conduit reconstructed via the posterior mediastinal route is very difficult . in addition , it is more invasive because it requires reconstruction with another organ such as the colon , jejunum , or skin , for the conduit . therefore , it is important to detect the lesion at an early stage so as to treat it with minimally invasive surgery such as endoscopic mucosal resection or partial resection . therefore , careful , periodic endoscopic evaluation after operation in the patient with esophageal cancer is needed . we had performed annual esophagogastoduodenoscopy evaluation and other radiologic studies twice in a year . in conclusion , a careful , periodic , and endoscopic evaluation after surgery for esophageal cancer is needed for early detection of other primary malignancies . in addition , surgical treatment of gastric conduit cancer after esophageal cancer surgery was found to be possible and safe in our experience .

we report a very rare case of surgery on gastric conduit cancer . a 67-year - old male patient underwent esophagectomy and intrathoracic esophagogastrostomy for squamous cell carcinoma of the lower thoracic esophagus 27 months ago . upon follow - up , a gastric carcinoma at the intra - abdominal part of the gastric conduit was found on an esophagogastroduodenoscopy . we performed total gastrectomy and esophagocolonojejunostomy in the manner of roux - en - y anastomosis . the postoperative course was not eventful and an esophagogram on the 10th postoperative day showed no leakage or stenosis of the passage . the patient was discharged on the 17th day with no complications .

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a 25-year - old female patient who earlier had implant placement in relation to 46 and 47 reported to our department for second stage surgery . 1994 , in which the attached mucosa at the top of the ridge is moved in a buccal direction at second stage surgery to obtain a papilla like formation and increased bulk of tissue around implants . the following steps are involved in this technique.([figure 1]-schematic representation ) technique ( hand drawn representation ) identify the location of the cover screws through the covering mucosa [ figure 2 ] make an incision at the palatal / lingual aspect of the cover screws , followed by vertical releasing incisions in the buccal direction . it is important to preserve the gingival cuff at neighboring teeth [ figure 3 ] elevate a full thickness flap in the buccal directionremove the cover screwsselect proper abutments and connect them to the fixtures [ figure 4 ] make semilunar bevel incisions in the buccal flap toward each abutment . start at the distal aspect of the most mesially located implant [ figure 5 ] disengage the pedicle , and then rotate it 90 in the palatal direction to fill in the inter - implant space [ figure 5 ] suture the tissues , allowing no tension within the pedicles [ figure 6 ] . identify the location of the cover screws through the covering mucosa [ figure 2 ] make an incision at the palatal / lingual aspect of the cover screws , followed by vertical releasing incisions in the buccal direction . it is important to preserve the gingival cuff at neighboring teeth [ figure 3 ] elevate a full thickness flap in the buccal direction remove the cover screws select proper abutments and connect them to the fixtures [ figure 4 ] make semilunar bevel incisions in the buccal flap toward each abutment . start at the distal aspect of the most mesially located implant [ figure 5 ] disengage the pedicle , and then rotate it 90 in the palatal direction to fill in the inter - implant space [ figure 5 ] suture the tissues , allowing no tension within the pedicles [ figure 6 ] . the clinical significance of attached gingiva around implants include prevent spread of inflammationprevents recession of marginal tissueprovides tight collar around implantsenable patients to maintain good oral hygiene . prevent spread of inflammation prevents recession of marginal tissue provides tight collar around implants enable patients to maintain good oral hygiene . this technique answered the above requirements , and yet it is very simple and provided excellent papilla like formation around implants . the healing abutment should be in place for 2 weeks for the tissues to heal like papilla [ figure 7 ] . healing after 2 weeks with healing abutments the patient was observed every 6 months , till 2 years . after 8 weeks , the final abutments were connected and noted that excellent soft tissue manipulation around implants created a perimucosal soft tissue contour matching the gingival architecture [ figures 8 and 9 ] . this thickness of tissue / seal around implants was present even after 1-year follow - up and 2 years follow - up periods [ figure 10 ] . postoperative restoration postoperative after 3 months two years postoperative mainly because of the thickness of mucosa obtained during the procedure , the patient was able to maintain the soft tissue around the implant with lesser plaque formation . moreover , a tight tissue barrier was created like natural dentition , which correlated well with the tissue barrier concept postulated by goldman and cohen . zone of gingiva would facilitate subgingival plaque formation because of improper pocket closure resulting from the movability of the marginal tissue . the absence of keratinized mucosa increases the susceptibility of peri - implant lesions and plaque - induced destruction . mehdi adibrad et al . reported that there is a significant influence of the width of keratinized mucosa on the health of the peri - implant tissues . the absence of adequate keratinized mucosa around implants supporting over dentures was associated with higher plaque accumulation , gingival inflammation , bleeding on probing , and mucosal recession . the thickness obtained with this technique resulting in less plaque accumulation and better maintenance correlated well with the studies reported above . in order to have better papilla like formation the following should be considered : careful handling of tissues in order to minimize trauma and maximize vascularizationbevel incisions in the mobile flaps should be delicate and should vary according to the needsrotated pedicles should be tension freesuturing technique should provide a tight and firm connection of pedicles to bone and abutments . careful handling of tissues in order to minimize trauma and maximize vascularization bevel incisions in the mobile flaps should be delicate and should vary according to the needs rotated pedicles should be tension free suturing technique should provide a tight and firm connection of pedicles to bone and abutments . it is imperative and proved by this case report that the operating surgeon should know the importance of papilla and attached mucosa around the implant . this case report was followed for 2 years and excellent prognosis obtained is very much evident [ figure 11 ] . this technique is simple and effortless in providing esthetic papilla formation and protective attached mucosa around implants .

peri - implant plastic surgery aims at improving the esthetic aspects of smile and masticatory function . over the years , several techniques such as tissue punch technique , full thickness flaps , and scalloping adjustment of flaps around implants have been employed ; it was very difficult to achieve a papilla like formation around implants . these added time and expense of the final results and led to undesirable complications . in order to overcome these difficulties , this case report describes a surgical technique where in papilla like formation and increase in width of attached gingiva around implants can be achieved with a single surgical procedure .

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distance between two genes was defined as the number of base pairs between their gene midpoints . relative distance refers to the distance of a tsg or a noncancer gene from an oncogene divided by the radius distance . the gene labels were randomly shuffled 10,000 times to generate new positions of oncogenes , tsgs and noncancer genes for the calculation of p - value . gene density is the number of tsgs or noncancer genes in a radius of specified distance divided by the radius distance . average density is the total number of all tsgs or noncancer genes on a particular chromosome divided by the length of that chromosome . a tumor types with cna profiles obtained by whole - genome sequencing were included in the present study . level 3 distance between two genes was defined as the number of base pairs between their gene midpoints . relative distance refers to the distance of a tsg or a noncancer gene from an oncogene divided by the radius distance . the gene labels were randomly shuffled 10,000 times to generate new positions of oncogenes , tsgs and noncancer genes for the calculation of p - value . gene density is the number of tsgs or noncancer genes in a radius of specified distance divided by the radius distance . average density is the total number of all tsgs or noncancer genes on a particular chromosome divided by the length of that chromosome . a tumor types with cna profiles obtained by whole - genome sequencing were included in the present study .

abstractfocal copy number gains or losses are important genomic hallmarks of cancer . the genomic distribution of oncogenes and tumor - suppressor genes ( tsg ) in relation to focal copy number aberrations is unclear . our analysis revealed that the mean distance of tsgs from oncogenes was significantly shorter than that of noncancer genes , suggesting that oncogenes and tsgs tend to be in close physical proximity in the human genome . such relationship was conserved in mouse and drosophila . pan - cancer analysis using data from the cancer genome atlas indicated that oncogenes without a nearby tsg are more prone to amplification . in conclusion , our study provides evidence for the nonrandom distribution of oncogenes and tsgs across different species . our data also support that the existence of a neighboring tsg can suppress amplification of an oncogene , shedding new light on a previously unappreciated protective mechanism of tsgs .

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it is incidentally found in autopsy specimens and surgical specimens with cryptorchidism and testicular germ cell tumor . this non - neoplastic lesion is usually seated in the mediastinum and septal part of the rete testis . it may present as a very small lesion detected in microscopic examination or a solid - cystic mass lesion which is macroscopically evident . in microscopic evaluation cryptorchidism was unilateral and the other testis was normal . there were no clinical or endocrine abnormalities . the testis measured 4 2.5 2.2 cm in size and there was no tumoral lesion in gross examination . on the cut section close to the testis parenchyma , there was a gland like tubular structures . some of these were in back - to - back position with little intervening stroma . the testicular parenchyma was comprised of seminiferous tubules that had sertoli cells only and no spermatozoa ( fig . ema ( novocastra ; 1/150 , clone gp 1.4 , newcastle , united kingdom ) and pankeratin ( novocastra ; 1/150 , clone ae1/ae3 , newcastle , united kingdom ) immunohistochemical stains were performed for diagnosis . adenomatous hyperplasia of the rete testis is a benign lesion which can appear at any time during life and was first described by nistal et al . . it is important to recognize tumor - like lesions of the rete testis to make an accurate differential diagnosis whether the lesion is benign or malign . ahrt etiology is not well understood yet but there seem to be associated conditions such as cryptorchidism , some kidney diseases , and germ cell tumors . our case was cryptorchid and seminiferous tubules near the lesion were lined by only sertoli cells and had no spermatozoa . the authors reported an adult case with ahrt in unilateral testis with no luminal spermatozoa . there are different cases such as prostate adenocarcinoma or embryonal carcinoma together with ahrt in the literature [ 6 , 7 ] . the true epithelial proliferation with gland - like or papillary proliferations replacing normal epithelium , continuous architecture of normal rete testis with adenomatous hyperplasia and lack of signs of malignancy are the proper diagnostic criteria for ahrt . in our case the differential diagnosis should include adenoma , papillary adenoma , primary and metastatic adenocarcinoma and rete testis cystic transformations with epithelial metaplasia . clinical history , localization , histologic features and immunohistochemistry are criteria for differentiating these lesions . complete surgical resection is the proposed therapy for ahrt cases and no report for recurrence has been identified . in conclusion , adenomatous hyperplasia of the rete testis is a rare lesion that can be confused with malignancy and should be remembered in the differential diagnosis of rete testis lesions .

there are several tumor - like lesions and miscellaneous neoplasms of the rete testis . we present a case with adenomatous hyperplasia of the rete testis ( ahrt ) . the patient was 24 years old with undescended testis and was referred to our hospital . there were no clinical or endocrine abnormalities . cryptorchidism was unilateral and the other testis was normal . right orchiectomy was performed and sent to the pathology laboratory for examination . morphologic and immunohistochemistry findings confirmed the diagnosis of ahrt in this case . the patient 's postoperative course continues uneventfully . ahrt is a rare lesion and can be confused with malignancy . it is incidentally detected in microscopic investigation . it may present as a very small lesion detected in microscopic examination or a solid - cystic mass lesion which is macroscopically evident . clinical history , localization , histologic features and immunohistochemistry are criteria for differentiating these lesions.we present this rare case for both surgeons and pathologists due to its importance as it can be confused with malignancy .

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teiser relies on calculating mutual information values between whole - genome measurements and millions of predefined structural motifs . the decoy / scrambled experiments and sirna knock - downs were performed using lipofectamin 2000 reagent ( invitrogen ) . for hybridizations , we used human 444k whole - genome human arrays ( agilent ) . isolation and identification of rna - binding proteins were based on previously published protocols . full methods and any associated references are available in the online version of the paper at www.nature.com/nature .

decoding post - transcriptional regulatory programs in rna is a critical step in the larger goal to develop predictive dynamical models of cellular behavior . despite recent efforts13 , the vast landscape of rna regulatory elements remain largely uncharacterized . a longstanding obstacle is the contribution of local rna secondary structure in defining interaction partners in a variety of regulatory contexts , including but not limited to transcript stability3 , alternative splicing4 and localization3 . there are many documented instances where the presence of a structural regulatory element dictates alternative splicing patterns ( e.g. human cardiac troponin t ) or affects other aspects of rna biology5 . thus , a full characterization of post - transcriptional regulatory programs requires capturing information provided by both local secondary structures and the underlying sequence3,6 . we have developed a computational framework based on context - free grammars3,7 and mutual information2 that systematically explores the immense space of small structural elements and reveals motifs that are significantly informative of genome - wide measurements of rna behavior . the application of this framework to genome - wide mammalian mrna stability data revealed eight highly significant elements with substantial structural information , for the strongest of which we showed a major role in global mrna regulation . through biochemistry , mass - spectrometry , and in vivo binding studies , we identified hnrpa2b1 as the key regulator that binds this element and stabilizes a large number of its target genes . ultimately , we created a global post - transcriptional regulatory map based on the identity of the discovered linear and structural cis - regulatory elements , their regulatory interactions and their target pathways . this approach can also be employed to reveal the structural elements that modulate other aspects of rna behavior .

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benign deep thoracic wall cyst is uncommon ; however , operative management using an endoscopic approach should be reserved primarily for symptomatic cases with multiple comorbidities , where multiple attempts at aspiration have failed because it is associated with less postoperative pain , lower morbidity and faster recovery [ 14 ] . a 62-year - old caucasian male presented with swelling and fullness in the left posterior chest . physical examination revealed a morbidly obese white male with a non - tender fluctuant mass on the left side of the upper back . the patient had two motor vehicle accidents that caused a lower right - sided lumbar injury . his past medical history was significant for hypertension , hyperlipidemia , sleep apnea , osteoarthritis , gastroesophageal reflux disease and chronic mild asthma . computed tomography ( ct ) scan of the chest demonstrated a large cystic mass between the posterior aspect of the thoracic ribs and deep to the muscles of the left back and scapula . chest magnetic resonance imaging delineated a large cystic mass extending from the level of the lower neck to just above the level of the diaphragm measuring 11 cm transversely , 4.5 cm anteroposteriorly and 23 cm craniocaudally ( fig . 1 ) . figure 1:(left ) chest ct scan shows the large cystic mass ( arrow ) between the left posterior ribs and muscles of the left back and scapula . ( right ) chest mri shows the large cystic mass extending from the level of the lower neck to just above the level of the diaphragm . ( left ) chest ct scan shows the large cystic mass ( arrow ) between the left posterior ribs and muscles of the left back and scapula . ( right ) chest mri shows the large cystic mass extending from the level of the lower neck to just above the level of the diaphragm . when the mass returned 2 weeks later , he was referred to our institution for further treatment . due to symptoms referred to the cyst and the lack of response to aspiration the patient underwent general endotracheal anesthesia and was placed in the right lateral decubitus position . a 2.5-cm longitudinal incision was made at a paramedian position on the left mid - back and it was carried through the level of the fascia by cautery . the paraspinous muscle fibers were separated and the bottom of the cyst was bluntly dissected free and the cyst was aspirated of its serous contents . the balloon was inflated to grapefruit size and left inflated for 2 min for hemostasis . the balloon dissector created a larger space beneath the cyst and along its lateral margins . the balloon was then replaced with a hasson trocar , and two additional 5-mm trocars were placed under direct vision to allow access to the co2-filled cavity ( fig . 2 ) . using a combination of blunt and electrocautery dissection , the cystic lesion was circumferentially freed from the trapezius muscle and cervical structures . once freed , the cystic mass was removed in its entirety through the hasson trocar site . two 15-french round jp drains were inserted through the 5-mm trocar sites and placed to grenade suction . histologic analysis of the unilocular cyst revealed a primarily fibrous wall with some adipose tissue and associated vasculature . the cyst lacked a true epithelial lining and any malignant features such as hypercellularity , hyperchromasia , cellular pleomorphism or increased mitoses ( fig . the final pathologic diagnosis was that of a benign , fibrous - walled cyst . while benign cysts are common within the skin and subcutaneous tissues of the posterior thorax , lesions deep to the muscles are rare . with aspiration of clear fluid devoid of malignant features , cysts such as these should undergo aspiration and , if reaccumulation occurs , repeat aspirations with injection of a sclerosing agent or surgical management are reasonable . with the potential need for repeated aspirations and sclerotherapy , our patient opted for cyst removal . while novel approaches are reported in abdominal wall surgery [ 1 , 3 ] , no reports document this technique for deep chest wall surgery . the balloon dissector and endoscopic resection facilitated free dissection of this large chest wall cyst . we have found no published reports of a deep thoracic cyst resembling our patient 's cyst in terms of histology or location . the differential diagnosis is not long , consisting primarily of seroma and secondarily of a synovial or ganglion cyst . these entities do not usually have a true epithelial lining , and they tend to occur in areas of previous trauma or surgery . our patient had undergone previous cervical spine surgery , which conceivably could be the cause of this cystic lesion . however , given its location off the midline , deep - seated nature against the rib cage , and virtually no scarring of the neck near the cyst , we believe that this cyst was unlikely related to the previous operation . other diagnoses to consider include sarcoma ( which can be ruled out by absence of malignant features on pathology ) , epidermal inclusion cyst ( unlikely given the large size , location deep to the dermal and subcutaneous region , and lack of squamous epithelial lining with keratinization ) and abscess ( unlikely given absence of inflammatory cells ) . given this patient 's cyst , it did not fit well into any of the above categories , our pathologists suggest that it is a benign and fibrous - walled cyst .

we present a 62-year - old male with a recurrent cyst in the left posterior chest . mri demonstrated a fluid - filled cavity measuring 23 cm in length and 11 cm in width . the cyst was aspirated demonstrating clear serous fluid . however , the cyst returned and he was referred to us for further treatment . the cyst was excised through a minimally invasive approach using a combination of blunt and electrocautery dissection . the cystic lesion was circumferentially freed from the trapezius muscle and cervical structures . pathologic examination revealed a benign , fibrous - walled cyst without a true epithelial lining . there are no published reports of a deep thoracic wall cyst resembling this case in terms of histology or location . this patient is free of recurrence 1 year later .

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organochloride insecticides are chlorinated cyclic hydrocarbons with molecular weights in the range of 300 - 550 da . they have a long half - life in the human body , and cause moderate toxicity . one of such insecticides is endosulfan ( 6,7,8,9,10 - 10 hexachloro 1,5,5a,,6,9,9a - hexahydro-6-methano-2,4,3-hexadithioxanthiepin 3-oxide ) , which has been widely used in agriculture since 1960 . the uncontrolled use of these compounds in developing countries has resulted in the deaths of animals and humans . there are isolated case reports of accidental and suicidal poisoning with endosulfan in the literature . acute poisoning is usually accompanied with nausea , vomiting , parenthesis , giddiness , convulsion , coma and respiratory failure . hepatic , renal and myocardial toxicity , agranulocytosis , aplastic anemia and skin reaction have been reported . if severe metabolic acidosis is present , hemodialysis may be an important intervention and should be performed early . till date , there is no case report from india for the management of endosulfan poisoning with severe metabolic acidosis and hypotension . by reporting this case , we emphasize the role of continuous renal replacement therapy ( crrt ) as a rescue therapy for endosulfan poisoning with severe metabolic acidosis and hemodynamic instability , even though it is a non dialyzable poison . a 32-year - old male was brought to casualty department on 13 of march 2009 with history of oral ingestion of a poison along with nausea , vomiting and three episodes of generalized tonic - clonic seizures with hypotension . on examination , the patient had progressive worsening of blood pressure and blood gas analysis was suggestive of high anion gap severe metabolic acidosis [ table 1 ] . arterial blood gas and other investigations of patient in view of high anion gap , metabolic acidosis with history of poisoning possibility of ethylene glycol poisoning was considered . he was treated with crystalloids , sodium bicarbonate and loaded with antiepileptic drug phenytoin 20 mg / kg . later midzolam infusion was started with rate of 5 mg / kg / h for repeated seizures.vasopressors were added as mean arterial pressure ( map ) was not responsive to fluid therapy . in view of repeated episodes of seizures , antiepileptic drugs were stepped up and the patient was started on infusion of thiopentone sodium with rate of 5 mg / kg / h . thiopentone sodium was continued for four days and then tapered . in view of worsening of general condition and severe refractory metabolic acidosis , a decision to start continuous venovenous hemodiafilteraion ( a form of crrt ) was taken . after starting of crrt , there was a slow but steady improvement in metabolic acidosis . within 3 - 4 h , blood pressure improved and hco increased to16 meq / l [ table 1 ] . initial serum creatinine was 1.8 mg / dl and the patient was having good urine output of around 2000 ml / day . his cpk - total , cpk - mb and liver enzymes were high on first day which gradually improved [ table 1 ] . after two days , his serum ph and bicarbonate normalized [ table 1 ] with no fresh episode of seizures . hence one session of potassium free conventional hemodialysis was given and the next day one more session of crrt was given for 48 h. hyperkalemia and sensorium improved and the patient was extubated on 26/3/2009 . on reevaluation of history from the patient and recovery of container by relatives , it was found to be endosulfan poisoning . there was gradual withdrawal of the antiepileptic and the patient was discharged in stable condition . the predominant toxicological effect is over stimulation of the cns , by inhibiting ca- and mg - atpase and antagonizing chloride ion transport in gamma - aminobutyric acid ( gaba ) receptors with little or no peripheral component . characteristic clinical signs following acute exposure are indicative of include seizures , nausea , vomiting , abdominal discomfort , hyperesthesia of the mouth and face , tongue and extremities , headaches , agitation , hyperactivity , in coordination , confusion , dizziness , and myoclonus . endosulfan is also toxic to the liver , kidney and lung , and can cause rhabdomyolysis in higher doses . his cpk enzyme was high and during later period of hospital course potassium was also high even with good urine output . the toxic effects generally seem to be completely reversible ; hence , it is necessary to identify the poison and to resuscitate the patient . a clinical diagnosis depends on a detailed history and suspicion and it may be necessary to measure concentrations of endosulfan for legal purposes . however , it has been reported that hemoperfusion is ineffective . phenytoin is probably less effective in these cases , given the effect of endosulfan on gaba receptors . in our patient , seizures were refractory to benzodiazepine , but controlled with infusion of thiopentone sodium . yavuz et al . , reported two cases of unintentional exposure to endosulfan , one of which presented with neurological manifestations , liver toxicity , and required mechanical ventilation and emergent hemodialysis ; the other had only neurological manifestations and liver toxicity . in literature , endosulfan poisoning with severe metabolic acidosis and hypotension has not been reported . in our case , the patient presented with severe high anion gap metabolic acidosis that responded well to crrt . in this case , predominant symptoms due to endosulfan poisoning were due to the involvement of the cns and severe metabolic acidosis . endosulfan poisoning should be suspected in unknown poisoning in the presence of primary cns manifestations , with or without clinical or laboratory evidence of other organ dysfunctions such as liver failure and high anion gap metabolic acidosis in tropical countries like india .

organochloride insecticides are chlorinated cyclic hydrocarbons . one of such insecticides is endosulfan ( 6,7,8,9,10 - 10 hexachloro 1,5,5a,6,9,9a - hexahydro-6-methano-2,4,3-hexadithioxanthiep in 3-oxide ) and it has been widely used in agriculture since 1960 . the uncontrolled use of these compounds in developing countries has resulted in the deaths of animals and humans . characteristic clinical signs following acute exposure are indicative of cns disturbances or overstimulation . mortality and morbidity rates are high and there is no specific antidote . we present an uncommon presentation of endosulfan poisoning in a 32-year - old male with high anion gap severe refractory metabolic acidosis . the patient was treated with continuous renal replacement therapy and was salvaged . till date , there is no case report from india for endosulfan poisoning with severe metabolic acidosis and hypotension . through this case report , we emphasize the role of continuous renal replacement therapy as a rescue therapy for endosulfan poisoning with severe refractory metabolic acidosis and hypotension , even though it is a non dialyzable poison .

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emphysematous cholecystitis ( ec ) is an uncommon variant of acute cholecystitis , which is caused by secondary infection of the gallbladder wall with gas - forming organisms [ 15 ] . the mortality rate of ec is as high as 25% because of its high complication rate [ 2 , 5 ] due to gangrene , gallbladder perforation , pericholecystic abscess and bile peritonitis . emergency surgical intervention is necessary for ec treatment for which open cholecystectomy has traditionally been performed [ 1 , 35 ] . here a 78-year - old male was admitted to our hospital for an investigation of vertigo . after admission , he developed fever and abdominal distention . a chest x - ray in the up - right position and abdominal computed tomography ( ct ) the chest x - ray showed the presence of gas within the gallbladder and in its wall ( fig . 1 ) . the ct scan revealed emphysematous changes in the gallbladder wall and air within the gallbladder ( fig . the patient was referred to the department of surgery and emergent surgery was performed . figure 1:up - right chest x - ray demonstrating air in the gallbladder ( arrow ) and in its wall ( arrowheads ) . figure 2:(a and b ) abdominal computed tomographic scans of axial and coronal views revealing emphysematous changes in the gallbladder wall and air in the gallbladder . up - right chest x - ray demonstrating air in the gallbladder ( arrow ) and in its wall ( arrowheads ) . ( a and b ) abdominal computed tomographic scans of axial and coronal views revealing emphysematous changes in the gallbladder wall and air in the gallbladder . based on the hemodynamically stable status of the patient , we selected a laparoscopic approach . exploration of the abdominal cavity revealed gangrene and necrosis of the gallbladder . to facilitate the resection , we initially punctured the gallbladder using a percutaneous needle to extract bile . although there was significant adhesion , we were able to safely dissect the calot 's triangle and detected a cystic duct and artery . his postoperative course was uneventful . a bile culture obtained during surgery revealed clostridium perfringens , enterobacter cloacae and enterococcus faecalis as the causative organisms . ec is an uncommon variant of acute cholecystitis characterized by potentially high mortality and morbidity because of a high incidence of gangrene or perforation . garcia et al . reviewed 20 cases of ec and reported that the mortality rate was as high as 25% and the morbidity rate as high as 50% . emergent surgical intervention for ec is indicated with cholecystectomy as the definitive treatment , although percutaneous cholecystostomy for critically ill patients presents another option [ 1 , 4 , 5 ] . bouras et al . reported that the laparoscopic approach for ec can be considered a safe procedure . owing to the advances of laparoscopic surgery , it has allowed to perform emergency cholecystectomy . our patient was hemodynamically stable ; therefore , we selected the laparoscopic approach , which was successfully and safely completed . the causative organisms of ec include c. perfringens , escherichia coli and species of the genera staphylococcus , streptococcus , pseudomonas and klebsiella [ 15 ] . ec is associated with diabetes mellitus and primarily affects males , as in the present case . the symptoms of ec are almost the same as those of acute cholecystitis , including right upper quadrant pain , nausea , vomiting and low - grade fever [ 2 , 4 ] . a prompt diagnosis of ec is essential and plain abdominal x - rays or ultrasound can be diagnostically useful with a sensitivity of up to 95% . however , contrast - enhanced abdominal ct scans may offer more information . in our patient , a chest x - ray in the up - right position detected air in the gallbladder wall and an abdominal ct revealed typical presentation of ec . emergency intervention is indicated and the laparoscopic approach can be considered a safe and effective method in hemodynamically stable patients .

emphysematous cholecystitis ( ec ) is an uncommon variant of acute cholecystitis , which is caused by secondary infection of the gallbladder wall with gas - forming organisms . the mortality rate of ec is still as high as 25% . emergency surgical intervention is indicated . open cholecystectomy has been traditionally accepted as a standard treatment for ec . we present a case of ec successfully treated by laparoscopic surgery . laparoscopic cholecystectomy for ec is considered to be safe and effective when indicated .

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the causes of pulmonary embolism can be venous thromboembolism , and nonthrombotic embolism like septic , fat , air , amniotic fluid and tumour embolism . tumour embolism to lungs can arise from cancers of breast , stomach , liver , kidney and rarely from choriocarcinoma . choriocarcinoma is a malignant , trophoblastic cancer , belonging to the malignant end of the spectrum in gestational trophoblastic disease , which can occur following molar pregnancy , ectopic pregnancy , abortion and even normal pregnancy [ 2 , 3 ] . choriocarcinomas spread via blood and lymphatics with early haematogenous spread to lungs , resulting in pulmonary embolism , pulmonary oedema , pulmonary hypertension or acute respiratory distress syndrome . in a young female presenting with persistent shortness of breath , cough and chest pain , the possibility of metastatic pulmonary embolism should be considered as surgery and chemotherapy can cure the choriocarcinoma metastasizing to the lungs . a 25-year - old lady was admitted in the pulmonology ward with the diagnosis of pneumonia . the patient had presented with a history of progressive shortness of breath , chest pain and persistent cough with occasional haemoptysis . she had a history of being treated with antibiotics and anti - tb drugs in outpatient basis . since her symptoms were persistent and her general condition was deteriorating , she was admitted to the ward . on examination , she had crepitations in bilateral chest and an oxygen saturation of only 80% . cect chest was done , which revealed pulmonary embolus occluding the main pulmonary artery , and right and left pulmonary arteries ( fig . 1 ) . serum beta - human chorionic gonadotrophin ( hcg ) level was found to be significantly high . she was managed further with chemotherapy ( emaco regimen ) with excellent response to the treatment . figure 3:histopathological image showing the trophoblastic elements . a ct scan image showing thrombus in the pulmonary artery . women in the reproductive age group with lung metastasis present with dyspnoea , chest pain , cough and haemoptysis . as the diagnosis can always be misleading and patient might be treated in the line of pneumonia or tuberculosis , it is very essential to have a high index of suspicion . surgery is indicated in patients with haemodynamic instability and those with massive tumour burden occluding main pulmonary and branch pulmonary arteries . so , chemotherapy should be initiated as soon as the diagnosis is strongly suspected or confirmed . pulmonary embolism due to choriocarcinoma should always be suspected in a reproductive age woman presenting with intractable shortness of breath .

pulmonary embolism carries a significant morbidity and mortality . metastatic choriocarcinoma presenting as pulmonary embolism is a rare event . here , we report a case of a 25-year - lady with a history of worsening shortness of breath for 4 months who was treated as a case of pneumonia and tuberculosis . owing to the worsening condition , she had a contrast enhanced computed tomography ( cect ) chest done and was diagnosed to have pulmonary embolism . she underwent pulmonary embolectomy . the histopathological examination of the embolus revealed it to be metastatic choriocarcinoma . she showed a good response to chemotherapy . metastatic choriocarcinoma should be considered as a differential diagnosis in females presenting with pulmonary embolism .

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

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

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for the self - assembling process , a solution containing 10 nm scaffold strand , 50 nm of each staple strand ( reverse - phase cartridge purified , bioneer inc . ) , 5 mm tris + 1 mm edta ( ph 7.9 at 20 c ) , 16 mm mgcl2 was heated to 80 c for 4 min , cooled down to 60c over the course of 80 min , and cooled further down to 24 c over the course of 72 h. the folded objects were electrophoresed on a 1.5% agarose gel containing 45 mm tris borate + 1 mm edta and 11 mm mgcl2 at 70 v for 3 h. to prevent the origami structures from denaturation during electrophoresis , the gel - box was cooled in an ice - water bath . the gel - band containing the structures was physically extracted from the gel and run through spin columns ( freezensqueeze spin columns , biorad ) at 5000 rcf . the dna tensegrity objects were then imaged with tem after negative staining with uranyl formate on a fei tecnai t12 biotwin at 80 kv . a 12-helix bundle kite with four springs of equal length ( 300 nt ) was designed such that the restriction site for ecori is located in one of the 300-nt spring regions . the assembled kites with a double - stranded region at the ecorri restriction site ( gaattc + 10 bases or more overhang on both sides of the sequence ) were incubated for one hour with the enzymes ( 20 l of 10 nm scaffold , 80 nm each staple , 1xneb - buffer 2 , 20 units of enzyme , new england biolabs , inc . ) . uncut and cut tensegrity kites were electrophoresed on a 1.5% agarose gel . the gel - bands were physically extracted and imaged with tem after negative staining with uranyl formate . for the self - assembling process , a solution containing 10 nm scaffold strand , 50 nm of each staple strand ( reverse - phase cartridge purified , bioneer inc . ) , 5 mm tris + 1 mm edta ( ph 7.9 at 20 c ) , 16 mm mgcl2 was heated to 80 c for 4 min , cooled down to 60c over the course of 80 min , and cooled further down to 24 c over the course of 72 h. the folded objects were electrophoresed on a 1.5% agarose gel containing 45 mm tris borate + 1 mm edta and 11 mm mgcl2 at 70 v for 3 h. to prevent the origami structures from denaturation during electrophoresis , the gel - box was cooled in an ice - water bath . the gel - band containing the structures was physically extracted from the gel and run through spin columns ( freezensqueeze spin columns , biorad ) at 5000 rcf . the dna tensegrity objects were then imaged with tem after negative staining with uranyl formate on a fei tecnai t12 biotwin at 80 kv . a 12-helix bundle kite with four springs of equal length ( 300 nt ) was designed such that the restriction site for ecori is located in one of the 300-nt spring regions . the assembled kites with a double - stranded region at the ecorri restriction site ( gaattc + 10 bases or more overhang on both sides of the sequence ) were incubated for one hour with the enzymes ( 20 l of 10 nm scaffold , 80 nm each staple , 1xneb - buffer 2 , 20 units of enzyme , new england biolabs , inc . ) . the gel - bands were physically extracted and imaged with tem after negative staining with uranyl formate .

tensegrity or tensional integrity is a property of a structure that relies on a balance between components that are either in pure compression or in pure tension for its stability [ 1,2 ] . tensegrity structures exhibit extremely high strength - to - weight ratios and great resilience , and are therefore widely used in engineering , robotics and architecture [ 3,4 ] . here we report nanoscale , prestressed , three - dimensional tensegrity structures in which rigid bundles of dna double helices resist compressive forces exerted by segments of single - stranded dna that act as tension - bearing cables . our dna tensegrity structures can self - assemble against forces up to 14 pn , which is twice the stall force of powerful molecular motors such as kinesin or myosin [ 5,6 ] . the forces generated by this molecular prestressing mechanism can be employed to bend the dna bundles or to actuate the entire structure through enzymatic cleavage at specific sites . in addition to being building blocks for nanostructures , tensile structural elements made of single - stranded dna could be used to study molecular forces , cellular mechanotransduction , and other fundamental biological processes .

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e - cadherin immunohistochemistry in foci of subpleural lipogranulomatous inflammation shows positive staining only in pneumocytes .

a 9-year - old , female , spayed , domestic longhaired cat presented to the ohio state university veterinary medical center oncology service with a 6-month history of changes in behavior and weight loss . the owner reported that the cat had become abnormally unfriendly and would growl or hiss when touched . the cat also had gait changes , manifested by left hind limb weakness , difficulty walking up stairs , and occasionally losing balance and falling down stairs . the cat was examined by its regular veterinarian and had abdominal radiographs , cbc , and biochemistry profile performed , which did not detect any abnormalities . on physical examination , the cat was underweight with an estimated body condition score ( bcs ) of 1/5 . neurologic examination revealed a very dull mentation , severe generalized muscle atrophy , and a slow , reluctant , and crouched gait . cranial nerve examination revealed no abnormalities . there was absence of conscious proprioception in all limbs . a forebrain lesion was suspected . the cat was examined 8 days later because of progressive signs of neurologic disease . the cat was obtunded and had a right head turn with a mild right head tilt . the gait showed proprioceptive / right vestibular ataxia with knuckling of both thoracic limbs on ambulation , a crouched posture , and a splaying outward of the left thoracic limb . there was a decreased menace response bilaterally that was worse on the left and decreased nasal sensation bilaterally . spinal reflexes were normal in all limbs . neurolocalization was to the right - forebrain with possible brainstem involvement . an abdominal ultrasound was then performed at the owner s request to investigate the gastrointestinal tract as a possible explanation for the weight loss , but no abnormalities were identified .

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