Datasets:

anumafzal94

/

pubmed-test-2048

like 0

common causes of haematochezia in adults are diverticular disease , vascular ectasia , colitis ( ischaemic , inflammatory or infectious ) , colonic neoplasia and anorectal conditions ( 1 ) . haematochezia is not reported as a common mode of presentation among patients with cronkhite - canada syndrome ( ccs ) in which diarrhea and dysgeusia are the predominant initial presentations ( 2 ) . surgery in patients with ccs has been carried out for associated gastrointestinal tract malignancies , intestinal obstruction and severe protein loosing enteropathy ( 3 ) . we present a case of persistent severe haematochezia in a patient with ccs , successfully managed with proctocolectomy . a 50-year - old sri lankan man presented with a 3-month history of diarrhoea , haematochezia and weight loss of 20 kg . one month prior to these symptoms he has noticed dark pigmentation of the skin and hair loss . physical examination revealed a cachectic man with alopecia , generalized skin hyperpigmentation involving the palms and onychodystrophy of fingernails ( fig 14 ) . diffuse skin hyperpigmentation involving the palms biochemical investigations revealed a haemoglobin value of 9g / dl and marked hypoalbuminaemia with serum albumin of 12g / l ( normal- 36 - 44g / l ) . upper gastrointestinal endoscopy and colonoscopy revealed multiple , sessile polyps of varying sizes distributed throughout the stomach , duodenum , colon and rectum without any polyps in the oesophagus . video capsule endoscopy revealed numerous similar polyps throughout the small intestine ( fig 4 ) . onychodystrophy of finger nails biopsy of colonic polyps revealed cystic dilatation of crypts with oedema of the lamina propria suggesting hamartomatous polyps . thus , a diagnosis of cronkhite - canada syndrome was made , considering the characteristic ectodermal abnormalities on physical examination , endoscopic findings and histology . haematochezia worsened despite medical treatment for 2 months and proctocolectomy with a permanent ileostomy was performed . histology of the specimen revealed multiple polyps with a diverse spectrum of morphologic features including juvenile - type polyps , adenomatous polyps , serrated adenomas , hamartomatous polyps and mixed polyps . first described in 1955 , cronkhite - canada syndrome ( ccs ) is a rare , nonhereditary polyposis syndrome with an uncertain aetiopathogenesis . approximately about 400 cases have been reported in the literature with the majority being reported from japan . it is characterized by the presence of diffuse gastrointestinal polyposis ( sparing the oesophagus ) associated with characteristic ectodermal abnormalities such as alopecia , nail dystrophy and cutaneous hyperpigmentation ( 4,5 ) . associations with raised ana and igg4 levels , hypothyroidism and various autoimmune diseases such as systemic lupus erythematous , rheumatoid arthritis and scleroderma have been published in the literature ( 6 ) . most of these patients present with diarrhea and dysgeusia and the dermatological manifestations are known to appear later ( 2 ) . the presentation in our patient is different because he had not developed dysgeusia , his cutaneous symptoms have preceded the onset of diarrhoea and haematochezia was one of his key presenting features . , different treatment modalities have been attempted with varying degrees of success ( 7 ) . these include hyperalimentation , corticosteroids , h2-receptor antagonists , antibiotics , acid suppression , cromolyn sodium , anabolic steroids , surgery , and combinations of these therapies ( 7 ) . among the various complications this can be as high as 15% and both gastric and colorectal malignancies are known to occur in these patients ( 8,9 ) . some studies have shown overall mortality rates as high as 55% among their patients ( 2 ) . to our knowledge , this is the first case of total proctocolectomy for refractory haematochezia in a patient with ccs . this also highlights the importance of considering cronkhite - canada syndrome as a rare possibility in a middle aged male presenting with haematochezia , specially if the patient is of asian origin and if there are any cutaneous abnormalities suggestive of this condition .

cronkhite - canada syndrome is an extremely rare condition of gastrointestinal polyposis in which the main presenting features are diarrhoea and dysgeusia . the polyps in this condition are characteristically distributed throughout the entire gastrointestinal tract except the oesophagus , and these patients exhibit unique ectodermal abnormalities . herein , we report a 50-year - old male who had recurrent episodes of severe haematochezia from the polyps in the colon . further examination and investigations revealed a diagnosis of cronkhite - canada syndrome . proctocolectomy was carried out for medically refractory haematochezia and the patient is asymptomatic at present .

balantidium coli ( b. coli ) is the only ciliated protozoan that is known to infect humans . balantidiasis is a zoonotic disease occurring in humans via the feco - oral route from the normal host , the pig . however , it may be found in rare extraintestinal sites such as liver , lung , and genitourinary tract . b. coli can become an opportunistic parasite in immunosuppressed hosts living in urban environments , where pigs are not a factor in infection . in this case report , b. coli was incidentally found in the urine of a patient having chronic obstructive pulmonary disease ( copd ) who was on steroids for a long time . the patient had no history of diarrhea , other gastrointestinal ( gi ) symptoms , previous urinary tract infection , or urethral discharge . he was also taking bone broth / soup . as a routine work - up urine sample was received . , several oval - to - oblong ciliated parasites that were approximately 75 50 m in size were seen swimming rapidly across the slide [ figure 1a ] . two to three pus cells per high power field and few candidal pseudohyphae and spores were also present . cytosmears were prepared from the urine sediment to identify the morphology . both hematoxylin and eosin ( h&e ) and giemsa staining were done . in h&e stained smears [ figure 1b ] , cytoplasmic food vacuoles and macronucleoli were seen and faint impression of cilia was noted . in giemsa stained smears [ figure 1c and d ] , the parasite was identified and the body was covered with short and delicate cilia that were all of uniform length . to exclude contamination , we examined two repeat urine samples that were collected under sterile condition . based on the morphology and swimming pattern , a diagnosis of urinary balantidiasis was made . oval - to - oblong ciliated trophozoites containing cytoplasmic food vacuoles ( thin arrows ) . ( b ) ( h&e , 40 ) trophozoites of b. coli in urine showing cytoplasmic food vacuoles and faint impression of cilia ( thick arrow ) . ( c and d ) ( giemsa , 40 ) trophozoite of b. coli in urine covered with short and delicate uniform length cilia ( thin arrows ) complete hemogram and biochemistry profiles were within normal limits . serology for human immunodeficiency virus ( hiv ) and hepatitis b surface antigen ( hbsag ) were negative . his fecal samples and bronchoalveolar lavage fluid samples were negative for trophozoites / cysts of b. coli . the patient was very sick at the time of admission , later he was intubated and kept on ventilator . malmsten was the first to recognize b. coli in two humans with dysentery in the year 1857 . the pig is the common reservoir of infection but the parasite is harmless to the host as the parasite thrives mainly on starchy food that is abundant in pig 's intestine . the scarcity of starchy food in the human bowel explains the rarity of balantidial infection in man . cyst is the infective stage , when ingested liberates trophozoites in the large intestine , which may remain in the bowel or may invade submucosal coat of the bowel . the trophozoites and cysts of b. coli are shed in feces and if the cysts , in particular , contaminate drinking water or food , the infection can be spread to other pigs or humans . the trophozoite measures 30 - 150 m in length and 25 - 120 m in width ; the cyst , which may be spherical or slightly ovoid , measures 40 - 60 m in diameter . the mouth ( oral apparatus ) is located at the tapering anterior end , and the cytopyge ( anus ) is located at the rounded posterior end . balantidium causes no serious disease of the gi tract ; however , in conditions such as malnutrition , alcoholism , or a compromised immune system , it can lead to disease . in our case , the source of infection is not clear . the patient had no history of contact with pigs , but he had history of intake of bone broth . third hypothetical possibility is the ascending infection from the urine pot that was washed with plain contaminated water . b. coli should be differentiated from trichomonas vaginalis ( t. vaginalis ) , entamoeba histolytica ( e. histolytica ) , ciliocytophthoria phenomenon . in urine it can be differentiated easily from b. coli by its morphology and motility . in stool , it moves on the slide surface by means of an anterior ectoplasmic pseudopod and is smaller ( around 25 m ) in diameter . in addition , mature cysts are smaller and quadrinucleate as compared to binucleate b. coli cysts . in case of samples taken from anatomic locales that are lined by ciliated columnar epithelium ciliocytophthoria are much smaller ( average 12 10 m ) anucleated cells with cilia along one edge . many cases of b. coli infection in the stool sample have been reported worldwide . however , in urine there were only a few case reports available . we have found only two case reports of isolated urinary balantidiasis from india while the rest showed coinfection with t. vaginalis . umesh reported a case of a 29-year - old woman with cystitis due to b. coli . reported urinary balantidiasis in a 68-year - old farmer having diabetes and chronic kidney disease . to the best of our knowledge , this is the third case report of isolated urinary balantidiasis from india . rapid spiraling motility and cytosmears stained with giemsa and h&e satins are very useful in morphological identification . effective sanitation , use of clean water , and consumption of properly cooked food are probably the most effective ways to prevent balantidiasis in humans .

balantidiasis is a rare zoonotic disease in humans . balantidium coli is the causative ciliated protozoan . we present a case of urinary balantidiasis in a patient having chronic obstructive pulmonary disease ( copd ) who was on steroids for a long time . he has no symptoms of bowel or urinary involvement . we are reporting this case because of its rarity in human urine and also for future references .

methylammonium iodide ( ch3nh3i ) was prepared by dissolving methylamine ( sigma - aldrich 534102 ) in absolute ethanol and reacting with hydroiodic acid ( sigma - aldrich 210021 ) in an ice bath . then , 12.4 ml of methylamine and 6 ml of hydroiodic acid were mixed with 50 ml of ethanol . the solvent was removed by rotary evaporation , and the obtained white powder was washed with anhydrous diethyl ether . ch3nh3i and pbcl2 ( sigma - aldrich 268690 ) were dissolved at a final concentration of 40 wt % in anhydrous n , n - dimethylformamide ( dmf ) ( the molar ratio between ch3nh3i and pbcl2 was 3:1 ) . mapbi3 films were grown onto clear white glass substrates ( proscitech ) previously cleaned sequentially in ethanol , acetone , 2-propanol , and finally treated oxygen plasma for 300 s. ch3nh3pbi3 precursor solution ( 100 l ) was deposited ( substrate area 2 cm 2 cm ) by spin - coating at 5000 rpm . after 6 s , while the spinning process took place , 200 l of anhydrous chlorobenzene was dropped onto the center of the substrate , as previously reported . the resulting films were then annealed at 100 c for 3 h , until a pure ch3nh3pbi3 layer was obtained . optical characterization . total transmittance ( t ) and total reflectance ( r ) spectra of the ch3nh3pbi3 films were measured using an integrating sphere attached to a uv vis spectrophotometer ( shimadzu uv-2101 pc ) . the spectral dependence of the absorptance ( a ) of the ch3nh3pbi3 films was determined by making use of the formula a = 1 r t. ple measurements were performed in a commercial fluorometer ( fluorolog 3 from horiba ) . the samples were excited with a spot of 1 1 cm with a wavelength variable between 450 and 850 nm ( fwhm = 5 nm ) , and detection was carried out at an angle of = 22.5 at the maximum of pl ( = 775 nm ) . pl measurements were carried out by optically pumping the samples with a tunable picosecond laser source ( fianium sc400 ) delivering low power ( sub - mw ) , 900 ps long pulses with a 1 khz repetition rate . the pump beam was focused down to a 100 m spot with an achromatic lens ( f = 10 cm ) , which also collected the emission . spectra were collected at 0.5 s intervals with a fiber - coupled spectrometer ( usb2000 from ocean optics ) .

the photophysical properties of films of organic inorganic lead halide perovskites under different ambient conditions are herein reported . we demonstrate that their luminescent properties are determined by the interplay between photoinduced activation and darkening processes , which strongly depend on the atmosphere surrounding the samples . we have isolated oxygen and moisture as the key elements in each process , activation and darkening , both of which involve the interaction with photogenerated carriers . these findings show that environmental factors play a key role in the performance of lead halide perovskites as efficient luminescent materials .

vascular lesions of the small intestine and colon are common causes of acute or chronic gastrointestinal hemorrhage , and arteriovenous malformations ( avms ) are an important vascular cause of obscure and intermittent gastrointestinal bleeding ( 1 ) . histologically , avms are persistent communications between thick - walled arteries and veins without intervening capillaries and are divided into true or congenital and acquired forms according to their locations and age at their presentations . although the endoscopic appearances of avms occurring in gastrointestinal tracts are not distinctive , some reported cases were observed as flat or mildly elevated hemorrhagic spots or erosions , while others have been appeared as polypoid masses . avms are usually small , single , and are located mainly in the rectum and descending colon in case of congenital or true avms , unlike acquired avms which are located mainly within the right colon . avms are relatively uncommon in the small bowel , and it is extremely rare that they present as a circumferential , transmural , and dilated vascular structure encasing only the terminal ileum and mimicking intestinal varicosis . we report a rare case in which a transmural avm mimicking intestinal varicosis and encasing the terminal ileum circumferentially . a 30-yr - old man was transferred to our hospital for the investigation and management of intermittent hematochezia for a 5-yr duration . on admission , he was not being prescribed a nonsteroidal anti - inflammatory drug , nor was suffering from portal hypertension or liver disease . there was no history of a peptic ulcer , and examinations of skin , oral , and anal mucosa revealed no abnormal findings . subsequent colonoscopy revealed a circumferential erythematous , nodular , and elevated lesion with hematocystic spots in the terminal ileum resembling varicosis ( fig . 1 ) . computed tomography ( ct ) scans with 3-dimensional angiographic reconstruction showed a vascular tuft located around the terminal ileum ( fig . 2 ) . to exclude other synchronous intraluminal sources of bleeding in the small bowel we performed enteroclysis , which revealed a segmental , nodular , and uneven elevated lesion with a length of 10 cm in the terminal ileum ( fig . the patient was treated by ileocecectomy , which encompassed the nodular and dilated vascular structure in the terminal ileum that resembled a varicosis lesion on gross inspection ( fig . 4 ) . surgical biopsy specimens revealed dilated vascular channels with a thickened wall involving the entire bowel wall and secondary arterialization of veins consistent with an avm ( fig . 5 ) . his postoperative course was uneventful , and the patient has been followed - up without a further episode of hemorrhage . despite dramatic improvements in diagnostic and therapeutic modalities , it is not always possible to determine the appropriate diagnosis and treatment for vascular lesions , such as , vascular ectasia , hemangiomas , dieulafoy lesions , and avms . in particular in the case of avms , no distinctive endoscopic or radiologic appearance has been elucidated because of their rarity , terminologic inconsistencies , and the diverse natures of their endoscopic morphologies . the presented case describes an unusual avm that involved the full thickness of the terminal ileum , mimicking intestinal varicosis on endoscopic and gross inspection . endoscopic finding of our case which demonstrates dilated and tortuously distended vascular tufts with red markings is a typical feature of intestinal varicosis ( 2 , 3 ) . the majority of avms reported are focal , flat , or mildly elevated with erythematous spots or erosions , and a minority of avms have polypoid or pedunculated masses ( 4 - 6 ) . a medline search revealed that only a small proportion of avms mimic intestinal varicosis with transmural involvement of the small and/or large bowel , and no endoscopic pictures were provided ( 7 - 9 ) . we found only one case of an avm with complete endoscopic pictures and gross pictures of dilated , tortuous , vascular tufts similar to our case . it involved the entire colon without displaying a vascular texture by angiography ( 10 ) . although avms can occur in jejunum ( 11 ) , the most common sites of involvement of true congenital avms are the rectum or sigmoid colon . many reports have suggested that they are most common in the cecum and ascending colon , but the terminologic confusion concerning the differentiation of angiodysplasia and acquired avms , which mainly develop in right colon , from congenital avms may have influenced the results . true avms are developmental and mainly occur in the rectum or sigmoid colon of patients younger than 50 yr , and correspond to type 2 lesions according to moore 's classification ( 12 ) . acquired avms or angiodysplasia correspond to type 1 according to this classification and occur in patients older than 50 yr . avms in younger patients tend to occur at atypical sites such as in the small bowel , but no segmental form of avm has been previously reported to involve only the terminal ileum in a cylindrical manner . the usefulness of ct for the detection of sources of gastrointestinal bleeding has been recently described in the context of imaging modality developments ( 13 ) . in the present case , we performed ct with a 3-dimensional angiographic reconstruction instead of conventional mesenteric arterial angiography because we did not consider invasive radiological therapeutic intervention as a potential elective hemostatic modality , and because we required an evaluation of the relation between the vascular architecture and the bowel wall . ultimately , surgical resection offers the best chance of curative treatment in such situations . in conclusion , we experienced a rare case of a segmental transmural avm involving the terminal ileum and mimicking intestinal varicosis , which presented as a case of recurrent lower gastrointestinal hemorrhage , and which was successfully treated by surgical resection .

we report on an exceptional vascular cause of gastrointestinal hemorrhage . a 30-yr - old man was admitted because of recurrent hematochezia . colonoscopy showed circumferential , erythematous , and nodular vascular distensions with hematocystic spots in the terminal ileum resembling varicosis and subsequent computed tomography with 3-dimensional angiographic reconstruction revealed a vascular architecture around the terminal ileum . no other potential source of bleeding was identified . the patient was treated by ileocecectomy and the final diagnosis was of an arteriovenous malformation confined to the terminal ileum . he has been followed - up without a further hemorrhagic episode .

potential incriminators are growth hormone , thyroid hormone , and gonadal hormone deficiency . growth hormone deficiency has been associated with endothelial dysfunction [ as evidenced by higher levels of plasminogen activator inhibitor - i levels ( pro - coagulant ) , loss of circulating cd34 + cells ] , increased total cholesterol , low - density lipoprotein ( ldl ) cholesterol , increased body fat ( truncal and waist hip ratio ) , decreased lean body mass and increased risk of hypertension . both central hypothyroidism and hypogonadism has also been associated with increased ( serum total and ldl cholesterol , homocysteine , ( c - reactive protein ) crp ) and impaired endothelial - dependent vasodilatation and insulin resistance . haffner et al . showed that the incidence of fatal and nonfatal myocardial infarction to be 3.5/100 person - years in nondiabetics as compared with 20.2/100 person - years in patients with t2 dm . a 62-year - old male patient coming from the interiors of maharashtra ( kolhapur ) , india , a nonsmoker , nonethanolic , on the background history of diabetes mellitus since the past 10 years , presented with sudden onset severe headache , right sided ptosis , for which he got admitted in a local hospital . imaging of the brain showed pituitary macroadenoma . within a few hours of admission he developed features suggestive of acute left ventricular failure secondary to acute coronary syndrome ( non - st - elevation myocardial infarction associated with elevated serum troponin t , regional wall abnormalities of mid and basal septum and apical and lateral wall of left ventricle on 2d - echocardiography . he discharged himself and was referred to our endocrine team by the cardiologist . on examination his observations read as follows : blood pressure 120/80 mmhg in right arm without any postural fall , pulse 84/bpm , elevated jugular venous pressure . baseline biochemical tests were normal except for an elevated creatine phosphokinase - mb 115 ( 4 - 36 iu / l ) and troponin - t 21 mcg / l ( 00.1 ) . follicular stimulating hormone ( fsh ) 0.79 m iu / ml ( 0.95 - 11.95 ) , luteinizing hormone ( lh ) 0.43 miu / ml ( 0.57 - 12.07 ) , total testosterone 0.88 ng / ml ( 1.56 - 5.63 ) , prolactin 1.14 ng / ml ( 3.46 - 19.4 ) , t3 53.49 pg / ml ( 58 - 159 ) , t4 6.74 ng / ml ( 4.87 - 11.72 ) , thyrotropin stimulating hormone ( tsh ) 0.08 miu / ml ( 0.2 - 6 ) , adrenocorticotropic hormone 68 pg / ml ( 10 - 100 ) , cortisol 17.4 mcg / dl ( 3.729.4 ) [ tests done while on hydrocortisone treatment ] , insulin like growth factor- 1 ( igf)-1 55.5 ng / ml ( 75 - 212 ) , with a serum sodium of 139 meq / l . 2d echo showed a reduced ejection fraction of 35% with septal and left ventricular apical and lateral regional wall abnormalities . dexa densitometry revealed severe osteoporosis at the level of both hip ( t - score magnetic resonance imaging ( mri ) pituitary [ figure 1a and b ] showed a sellar mass ( 2.2 1.3 cm in size ) causing compression of optic chiasma . ( a ) mri showing a sellar mass ( 2.2 1.3 cm in size ) causing compression of optic chiasma , ( b ) mri showing sellar mass compressing optic chiasma and invading cavernous sinus a coronary angiogram showed totally occluded right coronary artery proximally , 90% proximal stenosis of left anterior descending artery with heavy calcification and obtuse marginal 1 and 2 showing > 85% stenosis . a coronary artery bypass surgery was planned , which was undertaken successfully under appropriate steroid and thyroid hormone cover . after 4 weeks , he had complete resolution of his right sided 3 cranial nerve palsy . pituitary apoplexy refers to a clinical syndrome characterized by sudden onset headache , vomiting , visual impairment , and decreased consciousness caused by hemorrhage and/or infarction of the pituitary gland , which usually occurs in patients with preexisting pituitary adenomas and prolactinomas evolving over a period of hours or days . patients with hypopituitarism are subject to a significant increase in all cause mortality ( standardized mortality ratio being 2.06 for males and 2.8 for female ) and mortality from vascular disease ( standardized mortality ratio 1.4 for males and 1.7 for females ) . on the background of diabetes mellitus this cardiovascular mortality is amplified . the case described brings to light the need for an appropriate cardiovascular evaluation in patients with hypopituitarism especially if they have a background history of t2 dm . current practice in patients presenting with hypopituitarism is to provide appropriate hormonal replacement and follow - up is focused only on the pituitary gland . there may be an argument for aggressive cardiac evaluation and treatment in patients with t2 dm associated with hypopituitarism . this is the first case of pituitary apoplexy presenting as myocardial infarction to be reported from india .

we describe a male patient who presented with sudden onset severe headache and right sided ptosis that was diagnosed to be secondary to pituitary apoplexy on the background of diabetes mellitus . this was complicated by left ventricular failure and acute coronary syndrome . the case highlights the importance of considering hypocortisolism / hypopituitarism as an important and rare precipitant of an acute coronary event as occurred in the case .

a 62-year - old woman presented to the emergency department of central hospital bad berka with nausea and an episode of acute chest pain . she had been previously diagnosed with a myxofibrosarcoma of the left forearm ( april 2013 ) , which had been treated surgically . at that time , the maximal diameter of her ascending aorta was 47 mm , and anti - hypertensive therapy with a calcium - channel blocker was initiated . a contrast - enhanced computed tomography ( ct ) scan upon admission to the emergency unit showed an eccentric hypodense thickening of the ascending aorta and aortic arch . the maximal thickness of the intramural hematoma ( imh ) was 25 mm in the convexity of the ascending aorta and 10 mm in the aortic arch . moreover , no pleural effusion and only a small pericardial effusion were detected ( fig . despite the presence of an intramural hematoma , the patient s clinical symptoms did not recur , and she remained stable without progression of the pericardial effusion on echocardiographic follow - up . the imh was interpreted as a stable and non - emergency finding , and the patient was treated medically . due to an episode of recurrent chest pain , the patient was referred to our cardiac surgical unit the next morning . as a part of a preoperative work - up in preparation for urgent surgery , another follow - up ct scan was conducted . the rationale behind this decision was to determine whether the status of the imh had changed and to determine whether an intimal tear could be detected . to our surprise , significant regression of the aortic imh was found , with only minor residual thickening in the aortic arch and virtually no detectable hematoma in the ascending aorta ( fig . transesophageal echocardiography was then performed , demonstrating a complete disappearance of the imh ( fig . moderate aortic valve regurgitation was detected , showing no obvious changes in comparison with previous echocardiographic findings . although the patient remained asymptomatic , the recurrence of aortic imh was diagnosed 72 hours after the second ct scan . we were surprised to find a recurrence of aortic imh , especially since it predominantly involved the ascending aorta , with a maximal imh thickness of 12 mm ( fig . due to the recurrence of type a imh , in combination with the presence of aortic valve regurgitation and the increasing degree of pericardial effusion , the decision was made to undertake urgent surgery . intraoperatively , an unanticipated intimal tear was identified in the noncoronary sinus at the level of the sinotubular junction ( fig . regurgitation and moderate root dilatation ( an aortic root diameter of 45 mm ) , root replacement ( bentall technique ) using a bioprosthesis was conducted , as well as a partial aortic arch replacement . the patient s postoperative course was uneventful and she patient the unusual dynamics of this aortic imh are demonstrated in the frontal reconstructions of consecutive ct scans ( fig . aortic imh has often been diagnosed as a variant of aortic dissection using modern imaging techniques . it may present with the clinical symptoms of aortic dissection , and may occasionally precede overt aortic dissection or rupture . the clinical course of imh has been reported to vary , ranging from progression to an overt aortic dissection to complete disappearance over the course of follow - up . the serial changes of imh during follow - up have yet to be established , whereas its disappearance has been linked to a good long - term prognosis . we report herein a patient in whom two episodes of aortic imh ( stanford a , debakey i ) occurred within four days , influencing the surgical treatment strategy . aortic imh is a variant of overt dissection and may account for up to one of three to four cases of acute aortic syndrome . imh may completely resolve during follow - up , or it may progress to a classic aortic dissection . in the largest case series , reported by song et al . , the vast majority of the type a imh patients ( 84% ) were classified as being hemodynamically stable and hence were treated medically , resulting in a mortality rate of only 7.1% , whereas the international registry of aortic dissection reported a mortality rate of medically treated type a imh of as high as 33% . similarly to our patient , ohmi et al . reported a case in which an imh exhibited rapid regression , affecting the descending aorta during the initial presentation and involving the ascending aorta one year later . on both occasions , the imh regressed rapidly just hours after it was diagnosed . no aortic surgery was conducted due to the rapid and complete resolution of the imh . the phenomenon of the regression and/or disappearance of an imh is intriguing , and may explain to some extent the ongoing controversy with regard to its optimal treatment . nishigami et al . claimed that the disappearance of an imh suggests a good long - term prognosis . although no significant changes were observed during the course of follow - up among their patients with an imh that disappeared , they did not present guidelines regarding whether such cases of regressed imhs should be frequently checked for malign changes . therefore , the results from this single study should be interpreted with caution and can not be generalized to the entire spectrum of regressed imhs . progressive groups might be suboptimal , as it may only represent different stages of ongoing aortic disease . the clinical course of imh is very similar to that of a possible overt aortic dissection , mainly because an imh diagnosed using imaging techniques may precede an overt aortic dissection . although the resorption of an imh may occur without specific treatment , a substantial number of medically treated patients may suffer sudden cardiac death during the course of follow - up . therefore , no consensus has emerged regarding the most appropriate surveillance strategy in asymptomatic patients with a known history of the regression of an aortic type a imh . nevertheless , as previously reported , new - onset pericardial and pleural effusion have been reported to be more common in imh patients than in patients with an overt aortic dissection . due to the fact that our patient presented with these two indirect signs of imh - related complications and an initial imh thickness of 25 mm , a rather aggressive treatment strategy was chosen in order to prevent the possibility of impending sudden death . the definite decision to perform surgical treatment in the present patient was made due to the recurrence of an imh on the third ct scan , which demonstrated the malignant character of this case of acute aortic syndrome . despite aortic imaging by means of serial ct scans and transesophageal echocardiography , the intimal tear and overt aortic dissection furthermore , it remains uncertain whether the intimal tear remained undetected or developed secondarily during the course of the imh . nevertheless , the majority of patients undergoing surgical treatment for acute type a imh may present intraoperatively with an intimal tear . the lack of a visible tear on the ct scan may contribute to the delay of surgical treatment . this possibility means that the appropriateness of aortic imaging as currently implemented should be questioned , and further raises the issue of whether other markers would lead to more accurate decision - making in the treatment of acute aortic syndrome .

we report an interesting case in which overt aortic dissection mimicked two episodes of aortic intramural hematoma ( imh ) ( stanford a , debakey i ) . this took place over the course of four days and had a major influence on the surgical treatment strategy . the first episode of imh regressed completely within 15 hours after it was clinically diagnosed and verified using imaging techniques . the recurrence of imh was detected three days thereafter , resulting in an urgent surgical intervention . overt aortic dissection with evidence of an intimal tear was diagnosed intraoperatively .

ectopic thyroid is a developmental defect of thyroid gland that leads to presence of thyroid tissue at sites other than its normal cervical location . it is frequently found along the course of the thyroglossal duct but can also be found at remote distant sites . it is very rare to have two ectopic foci of thyroid tissue , and only a very few cases of dual ectopia have been reported in the world literature . in 70% of cases of ectopic thyroid , it is extremely rare to have dual ectopic thyroid with a normally located pretracheal thyroid gland . a seventeen - year - old female presented with history of a swelling at the base of the tongue first noticed about eight months ago . the swelling gradually increased in size causing dysphagia . there was no history of pain , ulceration , or bleeding from the swelling or any symptoms of airway obstruction . local examination revealed a pink 2.5 2.5 centimeter swelling covered with intact mucosa and visible vessels over it at the base of the tongue ( figures 1 and 2 ) . thyroid function test suggested primary hypothyroidism with tsh 31.6 miu / l ( 0.44.0 ) , t4 50.5 nmol / l ( 57.9161 ) , and t3 1.82 nmol / l ( 1.252.74 ) . ultrasonography of the neck showed normally located thyroid gland but both lobes were hypoplastic ( figure 3 ) . fnac from the swelling was done which showed thyroid follicular cells in loosely cohesive sheets , microfollicular as well as macrofollicular arrangements ( figure 4(a ) , 4(b ) , 4(c ) , and 4(d ) , 400x , mgg ) . a thyroid scan with technetium-99 m showed two foci of intense uptake , one at the base of the tongue and another in the submental region consistent with dual ectopic thyroid ( figures 5 and 6 ) . she has since been put on 100 microgram of levothyroxine daily and is on regular followup . ectopic thyroid was first described by hickman in 1869 in a newborn who was suffocated 16 hours after birth because of a lingual thyroid causing upper airway obstruction . lingual thyroid is the most common ectopic thyroid accounting for 90% of all cases with a prevalence between 1 : 100000 and 1 : 300000 and a clinical incidence between 1 : 4000 and 1 : 10000 . other sites of ectopic thyroid are suprahyoid and infrahyoid , lateral aberrant thyroid , substernal goiters , struma ovarii , and struma cordis . ectopic thyroid has also been found in larynx , trachea , oesophagus , pericardium , diaphragm , and branchial cysts . rare cases of ectopic thyroid are described in parathyroid , cervical lymph nodes , submandibular gland , duodenal mesentery , adrenals , and carotid bifurcation . ectopic thyroid occurs more commonly in females and are usually seen during adolescence and pregnancy when the demand for thyroid hormone increases . upto 70% of patients with lingual thyroid have hypothyroidism , and 10% suffer from cretinism . the thyroid gland is not found in its usual location in 70% of patients with ectopic thyroid . presence of two ectopic foci of thyroid tissue simultaneously is rare , and very few such cases of dual thyroid ectopia have been reported in the world literature . in an extensive review of the literature , sood et al . found that the mean age of these patients was 15 years , more common in females with an f : m ratio of 1.25 : 1 . the symptoms varied from asymptomatic to anterior neck swelling with or without altered thyroid status . in almost all of these patients , one site of ectopy was at lingual or sublingual region . familial dual ectopic thyroids with perihyoid ectopic thyroid and lingual thyroid have also been described . lingual thyroid can cause foreign body sensation in tongue , dysphagia , dysphonia , or sensation of choking . large blood vessels present on the surface of lingual thyroid predispose it for ulceration . all diseases capable of affecting the normal thyroid can affect the ectopic thyroid like adenoma , hyperplasia , inflammation , and malignancy . the rate of malignant transformation in ectopic thyroid is no greater than in normally placed thyroid . carcinoma of the lingual thyroid is a rare clinical entity with an estimated incidence of 1% . carcinoma of lingual thyroid presents in the same manner as a symptomatic patient with a lingual thyroid . therefore , for exact pathological diagnosis a biopsy should always be taken . in our case lingual thyroid usually has a poorly defined capsule that leads to intermingling of glandular tissue with muscle elements raising the suspicion of malignancy . the most important diagnostic modality for ectopic thyroid is a thyroid scan with technetium-99 m , but ultrasonography , ct scan , and mri may help in defining the extension and location of the ectopic thyroid gland . asymptomatic and euthyroid patients do not require any treatment , but they should be followed up and looked after for any complications . patients with raised tsh with swelling should be put on replacement therapy with thyroid hormone which can produce a slow reduction of the mass . when medical treatment fails or there are obstructive symptoms or haemorrhage or suspicion of malignancy , then surgery should be considered . as malignant transformation has been described , some authors consider complete excision of ectopic thyroid as an appropriate treatment in all cases .

dual ectopic thyroid is a rare presentation of thyroid ectopia . only a few cases have been reported in the world literature . dual ectopic thyroid in the presence of a normally located thyroid is even rarer . we report a case of dual ectopic thyroid in the lingual and submandibular areas in a seventeen - year - old female with hypoplastic thyroid gland in its normal location . the patient presented with a midline swelling at the base of tongue with dysphagia . thyroid function test revealed primary hypothyroidism . ultrasonography of the neck showed hypoplastic thyroid in its normal location . a thyroid scan with technetium-99 m pertechnate showed two intensely hyperfunctioning foci of ectopic thyroid tissue at a higher level in the midline consistent with dual ectopic thyroid , one at the base of tongue and the other in submental region . no uptake was seen in the normal bed .

she had previously been diagnosed with infiltrating ductal carcinoma in her right breast and had known metastases to the liver and bone . she had undergone a palliative right mastectomy and chemotherapy . when she first complained of horizontal diplopia , headache , and nausea , brain magnetic resonance imaging ( mri ) and cerebrospinal fluid analysis revealed no abnormal findings . her visual acuity was 20/20 in both eyes , and no abnormal findings were detected on slit lamp examination . the alternate prism cover test revealed 10 prism diopters of esotropia in the primary position . on two months later , both eyes were fixed in the midline on attempted right gaze . in contrast , left gaze was preserved in both eyes and vertical eye movements were normal ( fig . follow - up brain mri revealed an enhancing round nodular mass at the right facial colliculus of the lower pons , suggesting involvement of either the right abducens nucleus or the paramedian pontine reticular formation ( pprf ) along with the facial nucleus or nerve tract ( fig . the findings in our patient suggested impairment of the right abducens nucleus , which contains both motoneurons that control right eye abduction and internuclear neurons that control left eye adduction . involvement of the right pprf could also be inferred given a complete loss of right saccade movements of the right eye . moreover , the accompanying ipsilateral facial palsy supported the possibility of damage to the right facial nucleus or nerve tract in the vicinity of the abducens nucleus . on mri , a small tumor was found exactly at the facial colliculus of the lower pons ( fig . the preservation of adduction of the right eye on left gaze implied that the median longitudinal fasciculus ( mlf ) was intact . pathologic confirmation could not be obtained because we did not think the benefit of biopsy outweighed the risk of pontine injury . however , based on the mri findings and the slow progression of the neurologic deficits , a pontine tumor was favored . other potential diagnoses , including pontine hemorrhage , infarction , aneurysm , or demyelination , were excluded . the absence of hypertension and diabetes mellitus as well as an age younger than 55 years also supported the diagnosis . however , the patient 's history of liver and bone metastases along with a previous report indicating that brain metastasis was detectable in up to 30% of patients with breast cancer strongly supported the possibility of a metastatic lesion . in addition , metastatic brain tumors have been reported to be at least four times as common as primary brain tumors , and breast cancer is known to be the second most common cause of brain metastasis . yen et al . reported that the incidence of brainstem involvement in patients with breast cancer metastasis to the brain was as high as 12.4% , higher than that in patients with any other type of cancer . reported that 28% of cases of brain metastasis in breast cancer showed a single metastatic lesion , supporting the idea that a single brain lesion does not necessarily suggest a primary tumor . moreover , brainstem gliomas , the most common primary tumor of the brainstem , are usually slow - growing and progressive over several years ; the rapid growth in only three months also supported the diagnosis of metastatic cancer . neoplasm is known to be one of the causes of abducens nerve palsy and internuclear ophthalmoplegia . however , to the best of our knowledge , this is the first report of unilateral conjugate gaze palsy due to a pontine metastatic mass . while gaze palsy caused by herpes zoster infection or pontine hemorrhage has been reported , this is the first report of unilateral horizontal gaze palsy due to metastasis to the abducens nucleus . in conclusion , a localized metastasis to the abducens nucleus that spares the mlf can cause gaze palsy in a patient with breast cancer .

a 51-year - old woman with breast cancer presented with progressive diplopia . neuro - ophthalmologic examination revealed right gaze palsy and peripheral facial nerve palsy . brain magnetic resonance imaging ( mri ) was normal . however , two months later a repeat brain mri revealed an enhancing round nodular mass at the right facial colliculus of the lower pons , at the location of the abducens nucleus . localized metastasis to the abducens nucleus can cause gaze palsy in a patient with breast cancer .

an 18-year - old man presented with a soft tissue mass of five months ' duration in the right forearm . physical examination revealed a round , tender mass . on magnetic resonance scan of the right forearm , t1-weighted imaging revealed a circumscribed mass with intermediate signal intensity . the obtained slides were stained with hematoxylin and eosin and papanicolaou methods . on microscopic examination , the smear revealed clusters , sheets , and isolated cells in the background of myxoid materials ( fig . the nuclei were uniformly round to ovoid , with finely distributed chromatin and a small nucleolus . some cells had eccentrically - located nuclei and lesser amount of basophilic cytoplasm , resulting in a plasmacytoid appearance . neither mitosis nor necrosis was found . on immunohistochemical staining for cytologic slides , the tumor cells were occasionally positive for cytokeratin ( ae1/ae3 ) and s100 protein . the excised tumor measured 3.01.81.5 cm . the tumor was well - demarcated , yellow solid , soft , and myxoid ( fig . the tumor cells were present in solid sheets or reticular pattern without ductal component or necrosis . the tumor cells showed immunostaining for cytokeratin ( ae1/ae3 ) , epithelial membrane antigen ( ema ) , s100 protein , and glial fibrillary acidic protein ( gfap ) ( fig . soft tissue myoepithelioma is a rare tumor composed of neoplastic cells with features of myoepithelial differentiation . the tumor presents as a painless or painful mass in the dermis , subcutis , or deep soft tissue.3,4 while most myoepitheliomas are of salivary gland origin , they have been reported in the soft tissue , retroperitoneum,3 lung,5 and testis.6 the histogenesis of myoepithelial tumors arising in soft tissue is unknown . it likely reflects a different pattern of gene expression during oncogenesis rather than origin of a specific cell lineage.7 hallor et al.8 reported that a minimally deleted region of 3.55 mb at chromosome band 19p13 was identified in soft tissue myoepitheliomas . in the present case , the tumor consisted of epithelioid , spindle , and plasmacytoid cells forming solid sheets or reticular pattern in myxoid and fibrous stroma . the tumor cells revealed positive reaction for cytokeratin ( ae1/ae3 ) , ema , s100 protein , and gfap . the cytomorphologic and immunohistochemical features of the present case are similar to those of myoepitheliomas arising in the salivary gland.9 - 12 soft tissue myoepitheliomas , mixed tumors , and parachordomas are on the spectrum of tumor showing myoepithelial differentiation.1 characteristically , mixed tumor has more pronounced ductal differentiation , while parachordoma shows prominent cytoplasmic vacuolation . in the present case , ultrastructurally , myoepitheliomas show intermediate filaments , desmosomes , and basal lamina.13 intermediate filaments , desmosomes , and basal lamina were present in this case . soft tissue myoepitheliomas may be mistaken as other type of soft tissue tumors due to their cytomorphologically heterogeneous features . the differential diagnosis of soft tissue myoepithelioma includes mixed tumor , parachrodoma , schwannoma , smooth muscle tumor , ossifying fibromyxoid tumor ( ofmt ) , myxoid liposarcoma , extraskeletal myxoid chondrosarcoma ( emc ) , and metastatic carcinoma . immunohistochemically , parachordomas are positive for cytokeratin and s100 protein.14 schwannoma has wavy , point - ended nuclei in collagenous or myxoid background and nuclear palisading.15 smooth muscle tumor has cigar - shaped , blunt - ended nuclei and eosinophilic fibrillary cytoplasm.16 conversely , the cells of soft tissue myoepithlioma have more tapered nuclei . immunoreactivity for smooth muscle actin , desmin , and h - caldesmon supports a diagnosis of smooth muscle tumor . ofmt shows round and ovoid cells in myxoid matrix.17 ofmt is immunoreactive for s100 protein in approximately 70% of cases but negative for cytokeratin and gfap . myxoid liposarcoma shows lipoblasts and delicate , arborizing , thin - walled blood vessels in myxoid background.18 emc is characterized by spindle , stellate , or round cells in a myxoid or chondromyxoid matrix and shows variable immunoreactivity for s100 protein , neuron - specific enolase , and synaptophysin.19,20 generally , metastatic carcinomas show epithelial tumor cells with hyperchromatic nuclei , prominent nucleoli , and a high nuclear to cytoplasmic ratio . it can be excluded by the absence of immunoreactivity for s100 protein and myogenic markers . immunohistochemical expression for epithelial markers ( cytokeratin and/or ema ) , s100 protein or gfap is useful for confirmation of myoepithelial differentiation.3,7 although most cases of myoepithelial neoplasms of soft tissue are benign , approximate 20% have a risk for local recurrence.3 the histopathologic criteria for malignancy in soft tissue myoepithelial neoplasms are moderate to severe cytologic atypia , increase of nuclear to cytoplasmic ratio , nuclear pleomorphism , and readily identifiable nucleoli.2,3 no cytologic features of malignancy were present in this case of myoepithelioma . recognition of the cytomorphologic features of soft tissue myoepithelioma is necessary for the correct cytological diagnosis . soft tissue myoepithelioma should be included in the differential diagnosis of soft tissue epithelioid and spindle cell neoplasms .

soft tissue myoepithelioma is a rare neoplasm composed of myoepithelial cells . here , we describe the cytologic features of soft tissue myoepithelioma arising on the right forearm in an 18-year - old man . the excised tumor ( 3.01.81.5 cm ) was well - demarcated , yellow - gray , soft , and myxoid . the cytologic smears showed round to spindle , epithelioid , and plasmacytoid cells in the myxoid background . the nuclei were uniform , round to ovoid , with finely distributed chromatin and eosinophilic or pale cytoplasm . the tumor cells demonstrated immunoreactivity for cytokeratin ( ae1/ae3 ) , epithelial membrane antigen , s100 protein , and glial fibrillary acidic protein . electron microscopy showed intermediate filaments , desmosomes , and basal lamina .

this retrospective cohort study included pediatric and adult patients admitted to the university of iowa hospitals and clinics ( iowa city , ia , usa ) or to the university of maryland medical center ( baltimore , maryland , usa ) during 20032009 . first , we used codes from the international classification of diseases , ninth revision , clinical modification ( icd-9-cm ) , to identify patients with influenza - like illness ( ili ) ( 5 ) . this criterion was part of an initial study investigating influenza - like illness and s. aureus pneumonia ( j.s . patients were included in the study if they had respiratory cultures ( sputum , bronchial specimen , or tracheal aspirate ) that grew s. aureus and were tested for influenza before or during their admissions . if a patient was admitted > 1 time , only the admission with the first s. aureus positive respiratory culture was included . the primary outcome of interest , 30-day in - hospital mortality , was defined as death occurring in the hospital within 30 days of the first culture that grew s. aureus . the adapted charlson comorbidity index served as an aggregate score for co - occurring conditions ( 6 ) . the year of each patient s first positive s. aureus culture was dichotomized : 20032007 and 20082009 . we conducted bivariable analyses using either the test or the fisher exact test for categorical variables and the student t - test or wilcoxon rank - sum test for continuous variables . we used logistic regression to identify associations between potential predictor variables and 30-day mortality rates . variables associated with death ( p<0.25 ) in the bivariable regression analysis were examined for fit within the multivariable model and were retained if statistically significant ( p<0.05 ) . the year of each patient s first positive s. aureus culture was forced into the model . we analyzed data using sas software version 9.3 ( sas institute , cary , nc , usa ) . a total of 195 patients had > 1 respiratory culture that grew s. aureus and were also tested for influenza . sputum samples ( 115 , 59% ) and bronchial washes ( 50 , 26% ) were the most common respiratory specimens . respiratory or blood samples of 109 ( 56% ) patients grew methicillin - resistant s. aureus ( mrsa ) . most patients ( 166 , 85% ) were admitted to the university of maryland medical center ; 116 ( 59% ) were male , and median age was 42 ( interquartile range 559 ) years . of the 195 patients , 32 ( 16% ) had positive influenza test results . patients who had a positive influenza test were more likely to receive quinolones ( odds ratio [ or ] 3.30 , 95% ci 1.517.21 ) than were patients whose influenza tests were negative ( table 1 ) . patients who had a positive influenza test were significantly more likely to have the positive s. aureus respiratory culture collected < 2 days after hospital admission than were the patients whose influenza tests were negative ( or 3.27 , 95% ci 1.397.70 ) . of the 32 influenza - positive patients , 9 ( 28% ) died ; of the 163 influenza - negative patients , 18 ( 11% ) died ( or 3.15 , 95% ci 1.277.86 ; p = 0.021 ) ( table 2 ) . of the 9 influenza - positive patients who died , 5 had mrsa . among the 27 patients who died , those with a positive influenza test were more likely to have diabetes than those who had a negative influenza test ( 33% vs. 0% ; p = 0.029 ) . the multivariable logistic regression model found that , after statistically adjusting for year and time from admission to collection of s. aureus culture samples , patients whose influenza tests were positive had > 4-fold increased odds of death compared with patients whose influenza tests were negative ( or 4.31 , 95% ci 1.5711.83 ; p<0.005 ) ( table 2 ) . * defined as death occurring in the hospital within 30 d of the first respiratory culture that grew s. aureus . other investigators reported poor outcomes among patients who were co - infected with influenza viruses and s. aureus ( 3,4,7 ) . kallen et al . found a statistically significant increased risk for death among patients who had positive influenza test results and community - acquired s. aureus pneumonia , compared with patients who had negative influenza test results and community - acquired s. aureus pneumonia ( 7 ) . study included patients who had either mrsa or methicillin susceptible s. aureus pneumonia ( 7 ) but evaluated only 47 patients . the sample size for our study was much larger than previously performed studies , and we were able to examine mortality rates among patients who had a respiratory culture that grew either mrsa or methicillin - susceptible s. aureus . additionally , co - infection with influenza and s. aureus has been examined in animal models to identify mechanisms that cause poor outcomes ( 812 ) . severity of illness related to co - infection has been associated with a dysfunctional cell repair system and an altered immunologic response such as suppression of macrophage function , inhibition in phagocytic bacterial clearance , and cell damage to the airway system ( 812 ) . investigators have hypothesized that influenza damages epithelial cells in the respiratory system , providing opportunity for enhanced bacterial attachment ( 8,11 ) . once bacteria invade , cell destruction and fluid cause dysfunction of the airway system ( 8,11 ) . first , the investigation might have excluded patients who were tested for influenza at other facilities or who did not have laboratory - confirmed influenza . second , we could not determine whether the respiratory cultures that grew s. aureus represented infections or colonization . however , the information we describe remains clinically relevant because often clinicians do not know whether patients with positive s. aureus cultures are infected or colonized . diagnosing s. aureus pneumonia is challenging , and acquiring a lower respiratory culture such as a bronchial specimen or tracheal aspirate can be invasive and difficult to collect . therefore , if s. aureus pneumonia is suspected ( e.g. , symptoms and positive sputum culture ) , patients may be treated without a confirmed positive lower respiratory culture . third , our dataset did not include information about variables such as influenza vaccination status , mechanical ventilation , co - infection with organisms other than influenza and s. aureus , and whether the pneumonia was necrotizing . patients with a negative influenza test may be misclassified since we were unable to determine the time interval between the onset of ili symptoms and the collection of the influenza sample . last , influenza - like illness icd-9-cm codes were used to identify the cohort because the patients initially were included in a study of influenza - like illness and s. aureus pneumonia ( j.s . therefore , patients may have been missed if they had a respiratory infection with s. aureus and the condition or symptoms were not captured through an icd-9-cm code . in conclusion , among patients whose respiratory cultures grew s. aureus , patients with influenza were significantly more likely to die than were patients whose influenza tests were negative . interventions that increase influenza vaccination rates among patients at high risk for s. aureus respiratory infections may prevent both co - infection and death .

we retrospectively analyzed data for 195 respiratory infection patients who had positive staphyloccocus aureus cultures and who were hospitalized in 2 hospitals in iowa and maryland , usa , during 20032009 . odds for death for patients who also had influenza - positive test results were > 4 times higher than for those who had negative influenza test results .

plasma cell neoplasms are characterized by the neoplastic proliferation of a single clone of plasma cells , typically producing a monoclonal immunoglobulin . plasma cell neoplasms can present as a single lesion ( solitary plasmacytoma ) or as multiple lesions ( multiple myeloma ) . solitary plasmacytomas most frequently occur in the bone ( plasmacytoma of bone ) , but can also be found outside the bone in soft tissues ( extramedullary plasmacytoma).1 approximately 5% of all cases of plasma cell disorders are solitary plasmacytomas of the bone.2 however , the involvement of the pancreas is rare . we report a case of an extramedullary plasmacytoma of the pancreas diagnosed using ultrasonography - guided fine needle aspiration ( eus - fna ) with a review of the literature . a 58-year - old woman was transferred to our hospital for further evaluation of pelvic pain that was aggravated by walking and began approximately 2 months before admission . the initial laboratory tests showed a hemoglobin level of 10.6 g / dl , and blood urea nitrogen was 12.0 mg / dl . the level of total protein level was 9.7 g / dl and the albumin level was 3.3 g / dl . skeletal surveys detected a small osteolytic lesion without a sclerotic rim in the left parietal bone and a large bone destructive osteolytic lesion in the right inferior pelvic bone ( fig . further evaluation showed a serum free light chain lambda level of 3,475.3 mg / l and a 2-microglobulin level of 4.6 mg / l . contrast - enhanced abdominal computed tomography ( ct ) revealed a suspicious ill - defined marginated mass in the body of the pancreas ( fig . 2 ) . to further characterize the lesion , magnetic resonance imaging ( mri ) of the pancreas was performed . t2-weighted mri indicated that the pancreatic proximal body contained a mass of subtle high signal intensity ( fig . linear eus ( eu - me1 ultrasound system ; olympus , tokyo , japan ) ( gf - uct 240 ; olympus ) revealed a 1.21.0-cm sized , hypoechoic , heterogeneous , well - defined round mass in the pancreatic body ( fig . 4a ) ; fna was performed via a transgastric approach and five passages were made with a 22-gauge needle ( echotip ultra , echo-22 ; cook endoscopy , winston - salem , nc , usa ) ( fig . the cytopatholgy results showed a small cell neoplasm and the immunohistochemical profile was compatible with plasmacytoma ( fig . the patient began combination therapy consisting of bortezomib , mephalan , and prednisolone with local radiation therapy for the right pelvic bone lesion . multiple myeloma is a disease characterized by malignant proliferation of plasma cells typically involving medullary bones . extramedullary plasmacytomas represent 3% to 4% of all plasma cell neoplasms and have a male predominance , with a three to five times higher incidence in men than in women ; they usually occur in the sixth and seventh decades of life . approximately 80% to 90% of tumors develop in the head and neck area , although gastrointestinal involvement has been reported in 10% of cases . pancreatic involvement of myeloma is relatively rare , with an incidence rate of 2.3% based on autopsy studies . however , previous studies failed to describe the type of disease entity , and did not distinguish between multiple myeloma , myelomatosis , solitary bone myeloma , or extramedullary plasmacytoma.3 - 6 the radiological differentiation of extramedullary plasmacytoma of the pancreas from other pancreatic tumors such as poorly differentiated pancreatic neoplasm , lymphoma , and metastasis is difficult . most cases of plasma cell infiltration of the pancreas are microscopic , and well - formed masses are unusual . the latter may present as a focal mass or a diffuse enlargement of the pancreas ; typically , the patient presents with jaundice and abdominal pain related to the obstruction of the biliary tree because pancreatic plasmacytoma is often located in the head of the pancreas . in the present case , the mass was detected incidentally because it was located in the body of the pancreas . on ultrasound , pancreatic plasmacytoma appears as a multilobulated heterogenous or a homogenous hypoechoic mass . the ct features have been described as a focal multilobulated solid hypodense mass with homogeneous intravenous contrast enhancement or diffuse enlargement of the pancreas . mri features include pancreatic enlargement with a lobulated contour , lower signal intensity than that of the liver on t1-weighted images , and diffusely increased signal intensity on t2-weighted pulse sequences with heterogeneous enhancement.7,8 in our case , imaging findings were compatible with those of previous western reports . the diagnosis of an extramedullary plasmacytoma is based on evidence of a monoclonal plasma cell tumor outside the bone marrow . in the present case eus - fna has an excellent safety profile regarding the risk of pancreatitis , bleeding , and perforation . major complications have been reported in 2.5% of 355 patients who underwent eus - fna for a solid pancreatic mass.9 potential complications include acute pancreatitis , infection , and sedation - related complications ; no deaths have been reported.10 seeding of the needle track with tumor cells is rare . previous studies reported that the risk of seeding of pancreatic adenocarcinoma via eus - fna is 2.2% , which is low compared with that ( 16.3% ) of ct or transabdominal ultrasonography - guided percutaneous biopsy.11,12 moreover , seeding of a pancreatic extramedullary plasmacytoma during eus - fna is yet to be reported . in conclusion , we safely performed eus - fna in a patient with pancreatic plasmacytoma , and were able to provide an accurate visualization and histopathologic diagnosis . although there are approximately three case reports describing pancreatic involvement of multiple myeloma diagnosed by eus - fna in the english language literature,7,13,14 to the best of our knowledge , this is the first time it is reported in korea .

extramedullary plasmacytoma involves organs outside the bone marrow ; however , involvement of the pancreas is rare . we recently experienced a case of extramedullary plasmacytoma of the pancreas that was diagnosed by endoscopic ultrasonography - guided fine needle aspiration ( eus - fna ) . eus - fna , which has a high diagnostic accuracy and an excellent safety profile , is the modality of choice for establishing tissue diagnosis . we report a case of extramedullary plasmacytoma of the pancreas diagnosed using eus - fna .

in the previous issue of critical care , chen and colleagues investigate whether hydrocortisone influences the neurological outcome and mortality in a rat model of traumatic brain injury ( tbi)-induced critical illness - related corticosteroid insufficiency ( circi ) . up to 30 to 80% of tbi patients circi has been studied in sepsis but received much less attention after tbi , despite the fact that its incidence seems high . the authors postulated that early recognition of circi after tbi and treatment with corticosteroids may improve neurological outcome . this may prove important since bombardier and colleagues have shown that 51.3% of patients met the criteria for major depressive disorders during the first year after tbi . in the present study , chen and colleagues nicely demonstrate in a rat model of tbi that treating circi with hydrocortisone improves neurological recovery by blocking neuronal apoptosis , and reducing damage of the tight junction . interestingly , the authors also show that a synthetic glucocorticoid ( methylprednisolone ) did not alter neurological outcomes or mortality . hyponatremia is frequent after tbi , and recent evidence showed that mild hypernatremia could decrease the intracranial pressure , improving the cerebral perfusion pressure . second , after initial tbi , the exaggerated inflammatory response may cause circi by altering the function of the hypothalamic pituitary adrenal axis . tumour necrosis factor and interleukin ( il)-6 are increased in tbi or septic shock associated with circi . in particular , hoen and colleagues have shown that blood il-6 was significantly higher in severe trauma patients with circi as compared with patients without circi . it is well known that hydrocortisone decreases the production of these inflammatory cytokines , but recent evidence permits a reappraisal of the properties of hydrocortisone regarding the inflammatory response . in septic patients , hydrocortisone decreased the blood level of the anti - inflammatory cytokines ( il-10 ) and increased the blood levels of il-12 ( cytokine - enhancing immune response against bacterial infection ) without inducing immunosuppression . these data suggest that hydrocortisone is able to restore a balanced inflammatory response rather than inducing immunosuppression . third , corticosteroids are believed to be potent inducers of apoptosis mainly by a shutdown of the inflammatory response through inhibition of the nf-b pathway , which promotes survival of cells generally . these data were provided mainly with a high dose of synthetic glucocorticoids in patients with cancer or solid organ transplantation , but few data were published with hydrocortisone . chen and colleagues show that hydrocortisone prevents neuronal apoptosis even if the exact mechanism for this novel property of the drug remains largely unknown . the authors also demonstrate that hydrocortisone but not methylprednisolone improves neurological outcomes and prevents mortality in tbi rats . however , the benefit of corticosteroids in tbi patients remains controversial . in the crash study , a high dose of methylprednisolone worsened mortality as compared with placebo , and it was also speculated that hydrocortisone might increase the rate of secondary infections . in a recent cochrane systematic review , a stress dose of hydrocortisone ( 200 to 300 mg / day ) did not increase the rate of infection as compared with placebo in septic shock patients . in the hypolyte study involving severe trauma patients , including 65% tbi patients , the results obtained with hydrocortisone were spectacular in circi patients , whereas in the a priori planned subgroup analysis the treatment was particularly efficient in the tbi patients . answering the question of whether we should use hydrocortisone in tbi patients remains a subject of hard debate . detecting circi to select patients eligible for hydrocortisone treatment shows promise . the results of a large randomized multicenter study ( corti - tc ) will provide valuable data on the effects of hydrocortisone in severe tbi patients . circi : critical illness - related corticosteroid insufficiency ; il : interleukin ; tbi : traumatic brain injury .

data suggest that treatment of critical illness - related corticosteroid insufficiency after traumatic brain injury ( tbi ) with a stress dose of hydrocortisone may improve the neurological outcome and the mortality rate . the mineralocorticoid properties of hydrocortisone may reduce the rate of hyponatremia and of brain swelling . the exaggerated inflammatory response may cause critical illness - related corticosteroid insufficiency by altering the function of the hypothalamic pituitary adrenal axis , and hydrocortisone is able to restore a balanced inflammatory response rather than inducing immunosuppression . hydrocortisone could also prevent neuronal apoptosis . considering side effects , corticosteroids are not equal ; when a high dose of synthetic corticosteroids seems detrimental , a strategy using a stress dose of hydrocortisone seems attractive . finally , results from a large multicenter study are needed to close the debate regarding the use of hydrocortisone in tbi patients .

a 36-year - old man with repeatedly paroxysmal headache was admitted to our hospital . the patient suffered a severe head trauma in a car accident 21 days prior to the accident . he was admitted to hospital with periorbital soft tissue swelling , ct scanning revealed a skull fracture in sss area . before he was transferred to our hospital , computerized tomographic angiography ( cta ) revealed vascular malformation and venous congestion of the sss , which was considered to be secondary to the trauma . left internal carotid artery angiogram revealed a davf supplied by the anterior falx artery ( figure 1a ) . left lateral ( figure 1b ) , anteroposterior ( figure 1c ) and right lateral ( figure 1d ) view of left external carotid artery ( eca ) angiogram showed the sss davf with bilateral cortical venous reflux . endovascular treatment for a patient with posttraumatic dural arteriovenous fistula ( davf ) of the superior sagittal sinus ( sss ) . a ) left internal carotid artery angiogram before embolization showing the davf supplied by the anterior falx artery ; b , c and d ) lateral ( b&d ) and anteroposterior ( c ) view of left external carotid artery ( eca ) angiogram before embolization showing the davf of sss with bilateral cortical venous reflux ; e ) unsubtracted image showing the scepter balloon catheter navigated close to the fistulous point for onyx injection ( arrow head indicating the balloon markers , arrow indicating the distal tip ) ; f ) unsubtracted image showing the onyx cast extending to the proximal draining vein after embolization ; g ) post - embolization angiogram of the left common carotid artery showing complete disappearance of the fistula . h ) post - embolization angiogram of the right eca showing complete disappearance of the fistula . ( 415 mm , microvention , tustin , california , usa ) was placed at the most distal segment of the left middle meningeal artery ( mma ) and contrast medium was injected into the balloon . unsubtracted image showed the scepter balloon catheter navigated close to the fistulous point for onyx injection ( figure 1e ) . in order to occlude any residual fistula , onyx-18 ( ev3 , irvine , california , usa ) was then injected through the dual lumen balloon catheter positioned in one branch of the mma . unsubtracted image showed the onyx cast extending to the proximal draining vein after embolization ( figure 1f ) . with the balloon inflated , a total of 1.2 ml of onyx-18 was delivered with thorough penetration into the malformation slowly , after which , angiogram of both the left common carotid artery and the right external carotid artery ( eca ) showed complete disappearance of the fistula ( figures 1g - h ) . the balloon was deflated by syringe suction without difficulty . at the end of the procedure , the catheter was removed under constant aspiration without any noticeable adherence to the onyx cast . discussion dural arteriovenous fistula account for 10%15% of intracranial arteriovenous malformations.6 davfs in sss are extremely rare . a small percentage of patients have a history of previous trauma , they have been well reported.7 the common characteristic of davfs happened when a patient suffered skull fraction , or other trauma , not long after a head injury with progressive symptoms such as , exophthalmos , swelling of the eyelids , bruit , and so forth . this scenario most likely accounts for the findings in our patient , and we believe that his davfs probably were secondary to the head injury rather than a congenital anomaly . so far , the first - line treatment for davfs is embolization by using transarterial , transvenous , or occasionally , combined approaches.1 - 8 this approach proved to be effective comparable with davf obliteration in preventing neurologic morbidity with lower levels of procedural risk . the use of onyx has been increasingly reported for the treatment of davfs.2 - 10 using reflux as a plug , operator creates a forward flow of onyx , which is called the plug and push technique . the dual lumen balloon microcatheter served a dual purpose : the onyx-18 injection was allowed through the dual lumen balloon catheter and a mechanical barrier was provided to prevent the onyx reflux at the same time . this technique is an option during extracranial embolic embolization in a few select cases . in this case , a patient with a post - traumatic davf of the sss was effectively treated . it is appropriate to select a dual lumen balloon microcatheter for complex dural arteriovenous fistulas . using a dual lumen balloon microcatheter helps prevent onyx reflux and improves its penetration during onyx embolization of davfs . thus , this is a feasible and effective alternative approach for the management of post - traumatic davfs .

dural arteriovenous fistula ( davfs ) induced by trauma in the superior sagittal sinus ( sss ) are rare and difficult to treat because of their unique midline location , multiplicity of arterial feeders , and critical venous drainage . we report a case of an endovascular treatment using dual lumen balloon microcatheter on a patient with post - traumatic sss davf . by the use of dual lumen scepter balloon microcatheter , proximal onyx reflux was prevented . in this case , complete embolization of the davfs was achieved and the outcome of the patient was fairly good .

resuscitation from hypotensive circulatory shock is often more complex than just giving intravascular fluids . even in fluid - responsive hypotensive patients , vital organ perfusion may remain compromised despite fluid infusion if the mean arterial pressure ( map ) does not also increase with increasing cardiac output ( co ) . garca and colleagues suggested an approach that would predict whether the hypotensive patient would increase their map in response to intravascular fluid loading . there is a tight correlation between positive - pressure ventilation - induced changes in arterial pulse pressure ( pp ) , called pulse pressure variation ( ppv ) , and fluid responsiveness . ppv is calculated as the ratio of difference between maximum and minimum pp to their mean as assessed over about 5 breaths or 20 seconds . not surprisingly , subsequent studies showed that similarly calculated stroke volume variation ( svv ) , when measured independently , also predicted volume responsiveness . importantly , pp is created by stroke volume ( sv ) into the central arterial compartment as quantified by a transfer function . if arterial elastance ( ea ) and compliance remain constant , then aortic pp will vary directly with sv . if the bedside physician wants to know whether their hypotensive patient will increase their map in response to fluid loading , then they need to know two things . first , is the patient volume responsive ? if the patient is not responsive , then volume loading will not increase co. second , the physician needs to know the patient 's vasomotor tone . if the patient has marked vasodilation , as commonly occurs in septic shock , then map may not increase in response to fluid loading even if co does . to know whether a fluid - responsive patient is also pressure responsive the reciprocal of compliance is ea , which defines the pp / sv relation . increasing vasomotor tone increases both map and pp relative to co and sv . if one knew both ppv and svv , their ratio would define a dynamic ea ( eadyn ) . theoretically , map and pp should co - vary with changes in co if the heart rate remains constant . we previously predicted that ppv / svv > 0.8 would define pressure - responsive subjects if co increased . relative to this construct , garca and colleagues examined the ability of the ppv / svv ratio , deferred to as eadyn , to predict changes in map in 25 hypotensive patients with preserved volume responsiveness ( defined as map < 65 mmhg or systolic blood pressure < 90 mmhg and svv > 10% ) . using a standard 500 ml colloid fluid bolus , the authors defined map responders as those with a > 15% increase in map . they found that a baseline eadyn value > 0.89 predicted > 15% map increase after fluid administration with a sensitivity of 94% ( 95% confidence interval = 69.8 to 99.8% ) and a specificity of 100% ( 95% confidence interval = 66.4 to 100% ) . their clinically derived eadyn threshold of > 0.89 is remarkable similar to our > 0.8 value based on vascular modeling . importantly , as long as the ppv and svv values are great enough to define a slope , this relationship will remain constant and predictive even during spontaneous ventilation and with cardiac arrhythmias because eadyn is independent of volume responsiveness . since all of the commercially available arterial pressure - derived co monitoring devices report ppv and svv , this added eadyn parameter to define those patients needing vasopressors earlier in their management should have a significant impact on resuscitation efficacy . before embracing this approach and these findings totally , caution needs to be used in its routine bedside application . eadyn is a measure of arterial stiffness , which is itself partially determined by vasomotor tone . ea increases with age , with the expression of atherosclerosis and with aortic cross - clamping during aortic vascular procedures . for all these conditions , however , if sv increases then pp will also increase . regrettably , map may not increase as much as pp because diastolic pressure may remain constant . furthermore , pp can be independently increased by increasing left ventricular ejection velocity . to the extent that inotropic agents are being used , one may presume an increase in map not realized by increasing co even if eadyn > 0.89 . the above study , how - ever , used an arterial pulse contour estimating method to derive co and svv , and herein rests a potential problem . much attention has focused on using arterial pulse contour analysis devices at the bedside to measure co and svv from the arterial pulse . unfortunately , most indwelling arterial catheters sample a more peripheral arterial pressure signal , whose waveform may be altered in unexpected ways as the arterial tone , pulse wave velocity and left ventricular contractility vary . although this variability in co estimates can be readily improved by calibration , it will not improve the accuracy of the ppv / svv relation ( that is , eadyn ) . the eadyn accuracy is intrinsic to the assumptions used by each device to estimate svv . this is because ppv can be measured directly and is accurate when compared with ppv measured manually . all arterial pressure - sensing devices that estimate co do so by assuming a constant ea . how , then , is it possible for an algorithm that uses arterial pressure to calculate co to show differing changes in pp relative to sv over time ? the three major commercially available monitoring devices , however , do not share the same shoe size - the variance amongst these devices to estimate changing co is significant . the flotracdevice estimates svv from the standard deviation of the individual arterial pressure values over single beats averaged over 20 seconds . assuming the sv variance has a normal distribution , this assumption is valid for calculating svv . importantly , svv as a time - series function may not be normally distributed during atrial fibrillation and with vigorous spontaneous inspiratory efforts . how much error such non - normal distribution would introduce into the svv calculation is not known , but on theoretical modeling the degree of non - normal distribution would need to be great for it to affect svv by the standard deviation method . the picco uses a proprietary algorithm based on the ventriculo - arterial coupling transfer function to calculate co. this co estimate is averaged over 20 to 30 seconds and is quite accurate . however , since the picco no longer reports individual sv values on a beat - to - beat basis , it is unclear how it derives svv . the lidco uses a simple power transfer function to estimate sv on a beat - to - beat basis and calculates co from the mean sv values . to the extent that this power transfer function is accurate over time , the svv estimates should also be accurate . since this device does not use the pulse contour , the lidco remains accurate with dampened arterial pressure signals . accordingly , although each device reports ppv and svv values , the cross - correlation amongst devices based on their different algorithms is poor . validation of eadyn thus needs to be done independently both for each device and for different types of patients before this new bedside parameter is used for clinical decision - making . co : cardiac output ; ea : arterial elastance ; eadyn : dynamic arterial elastance ; map : mean arterial pressure ; pp : pulse pressure ; ppv : pulse pressure variation ; sv : stroke volume ; svv : stroke volume variation .

assessment of vasomotor tone is essential in defining appropriate resuscitation strategies for the hypotensive patient . although changes in mean arterial pressure to cardiac output define arterial resistance , resistance is only one component of vasomotor tone . compliance is the other component . the reciprocal of compliance is arterial elastance ( ea ) . importantly , dynamic ea can be estimated by the pulse pressure variation to stroke volume variation relation . dynamic ea is only one component of vasomotor tone , however , and increases in pulse pressure may not be proportional to increases in mean arterial pressure . also , devices that use the arterial pressure pulse to calculate the stroke volume have an inherent bias that is different amongst devices based on their transfer function algorithms . the use of dynamic ea for clinical decision - making thus needs to be validated separately for different devices and types of patients .

the incidence of primary cardiac tumors is low , at 0.001% to 0.03% [ 1 - 3 ] . the advent of variable cardiac imaging modalities , including echocardiography and multidetector computed tomography ( ct ) , has led to the identification of an increasing number of cases of asymptomatic cardiac tumors . cardiac papillary fibroelastoma ( cpf ) is a rare and benign cardiac tumor that can arise anywhere in the heart , but usually involves cardiac valves . moreover , the incidence of cpf in the left ventricle is lower than that in other parts of the heart . here we report a case of left ventricular cpf detected by echocardiography and successfully surgically resected . a 65-year - old woman was referred to our cardiology department for evaluation of a cardiac mass of the left ventricle . prior to the referral , she was admitted to another hospital with a complaint of chest pain of 3 days ' duration . coronary angiography and echocardiography coronary angiography showed no significant coronary disease , but a mass was found by echocardiography . she had been treated for hypertension and a stroke she suffered 5 years prior . on physical examination , her blood pressure was 110/70 mmhg , and her pulse rate was 62 beats / min . transthoracic echocardiography revealed a 1.8 1.7 cm highly mobile round mass attached by a stalk on the apical inferior wall of the left ventricle with an echolucent area ( fig . ct of the chest showed a 1.9 1.6 cm round and pedunculated mass with soft tissue density on the apical inferior wall of the left ventricle ( fig . on opening the left atrium , there was a mass attached deep to the inferior wall of the left ventricle . the resected tumor was 1.8 1.5 cm and had the appearance of a sea anemone ( fig . histology showed that the lesion had a papillary configuration with an avascular connective tissue core ( fig . among primary cardiac neoplasms , benign tumors account for 63% and malignant tumors for 37% . the mean age at diagnosis of cpf is approximately 60 years , although it has been reported in teenagers and children . cpf affects both sexes , but males predominate in most series . in the study of a series at the mayo clinic from 1957 to 2001 , of 110 primary cardiac tumors that were surgically removed a recent study reported that cpf represented 5% of primary cardiac tumors in 21 patients . in a report of 110 cpf cases , about 90% of cpfs appeared on cardiac valves , and the remainder originated from nearly all portions of the non - valvular endocardium , including the left ventricular septum , the left ventricular mural endocardium , the right ventricular outflow tract , the right atrium , the atrial septum , the papillary muscle , the chordate tendinea , the eustachian valve , and the chiari network . they have a gelatinous membrane on the surface and a stalk with multiple papillary projections . microscopically , cpfs are composed of a central stalk with radiating villus - like projections . the papillae are avascular structures , containing a core of dense collagen fibers admixed with varying amounts of reticulin and elastin fibers . the microscopic structure of a cpf closely resembles that of chordea tendineae , which prompted some to propose a hamartomatous - like pathogenesis . a cpf is a collection of avascular fronds of dense connective tissue lined by endothelium . however , it is deemed to be a reactive process rather than a true neoplasm . it is suggested that cpf may be associated with lambl 's excrescence and shear stress , and congenital factors may be involved in its development ; however , the cause remains unclear . with improved echocardiographic resolution due to higher transducers and new imaging modalities , cpf was considered to be an incidental autopsy finding and to have no clinical significance in the past . the clinical presentation of a cardiac tumor is determined by its location , size , and mobility . in particular , left - sided , larger sized ( 1 cm ) and highly mobile tumors have a higher incidence of embolization . cpfs have a predilection for the left side of the heart . in a review of the literature regarding complications in 79 cases of cpf , 61 lesions occurred on the left side of the heart , whereas only 18 were right - sided . cpfs are generally slow growing tumors , but may serve as nidi , allowing formation of large superimposed thrombi over a short period of time . symptoms include cerebral infarction and transient cerebral ischemic attack associated with soft and fragile fibroelastoma in 44% of patients , angina pectoris in 18% , myocardial infarction in 10% , cardiac failure in 9% , and sudden death in 8% . symptomatic cpf should be resected surgically ; however , there are no guidelines for the treatment of asymptomatic cpf . large , left - sided mobile tumors should be excised to prevent sudden death and emboli . small , non - mobile tumors may be followed with serial echocardiography and removed if they increase in size or become mobile or symptomatic . various methods have been proposed for complete excision of left - sided cpfs to avoid a left ventriculotomy due to further complications . for tumors deep within the left ventricular cavity close to the apex , the use of a cardioscope passing through the aortic or mitral valve is recommended to avoid damage to the valvular apparatus . in our case , we used a surgical approach through the left atrium and mildly pushed up the left ventricular apical inferior wall for easy resection of the mass . recently , a case in which a cpf deep in the left ventricle was resected under the guidance of a gastrointestinal fiberscope was reported . in this report , we present a case of cpf attached to the left ventricular apical inferior wall , which was successfully removed surgically .

cardiac papillary fibroelastoma ( cpf ) is a rare and benign primary cardiac neoplasm of unknown prevalence . the incidence of cpf in the left ventricle is lower than that in other parts of the heart . a 65-year - old female was referred to our cardiology department for evaluation of a cardiac mass of the left ventricle . transthoracic echocardiography revealed a 1.8 1.7 cm highly mobile round mass attached by a stalk to the apical inferior wall of the left ventricle with an echolucent area . the mass was successfully removed without any postoperative complications and was identified as a cpf .

tear fluid drains through the lacrimal punctum into the lacrimal canaliculi ; it then flows through the lacrimal sac and the nasolacrimal duct before being absorbed by the nasal mucosa . when this pathway becomes blocked , the resulting condition is known as nasolacrimal duct obstruction , which may be either congenital or acquired . over the last 15 years , our clinic has experienced 64 cases of nasolacrimal duct obstruction , all of which were successfully treated with lacrimal passage irrigation . in this procedure , 0.4% xylocaine ophthalmic solution is injected using a 1-ml syringe tube and a lacrimal passage irrigation needle , with the tip of the needle being inserted into the inferior lacrimal punctum pointing toward the nose and facing slightly downward . to facilitate irrigation , the patient is asked to snort in order to create negative pressure in the nasal cavity . once the patient has registered the bitter taste of the xylocaine , irrigation should be performed repeatedly with physiological saline . in these 64 cases , we performed at least 10 irrigations for each patient , and for some , we performed 50 or more . of the 64 cases , recurrence only occurred in the 1 case that we present here . in this patient , the blockage resulted from rice grains ingested over a period of many years , forming an obstructive mass . the patient , a 39-year - old male who works as a surgeon and is the lead author of this report , experienced abnormal lacrimation of the left eye while at work . however , the condition recurred 5 times during the following 2 years despite repeated irrigation on each occasion . during the sixth treatment , after approximately 20 irrigations had been completed , an object was suddenly ejected into the rear of the patient 's nasal cavity . on histological examination , this object was found to be an agglomeration of rice grains ( fig . 1 , fig . 2 ) and was believed to have penetrated the nasolacrimal duct over a long period via reflux through hasner 's valve . this mass then became molded into a rectangular , cone - shaped plug , matching the shape of the nasolacrimal duct . since this successful treatment , there has been no further recurrence . approximately 1 month after completing treatment , the author underwent detailed examination of the paranasal sinuses by an otolaryngologist using fiberscopy . although it was not possible to view up to hasner 's valve , no other abnormalities were noted within the range visible by fiberscopy . to the best of our knowledge , there have been no other reported cases of nasolacrimal duct obstruction caused by the retention of foodstuffs . the patient had a habit of talking while eating , and we concluded that a rice grain had at some point penetrated the orifice of the nasolacrimal duct from the nasal cavity side via reflux through hasner 's valve . this led to incomplete valve closure and allowed the subsequent entry of a succession of rice grains , coalescing into a single mass and causing the blockage . in this case , the nasolacrimal duct appears to have been nearly completely obstructed by a lump of rice . during initial treatment , neither anesthetics nor physiological saline solution could pass through the duct , instead pouring out of the inferior punctum . in the latter phase of treatment , as the lump of rice started to slowly drop down into the paranasal sinus , water was gradually able to pass through the site despite meeting some resistance . when the lump of rice emerged from the paranasal sinus , this resistance to passing physiological saline solution disappeared and the patient suddenly felt physiological saline solution flow into the paranasal sinus . backflow caused the rice grain to initially enter the nasolacrimal duct , after which deposits built up over a number of years to cause an obstruction . we then started to treat this with flushing , which could not have caused the backflow considering the chronology , because there is no possibility that backflow occurred as a result of flushing . nasolacrimal duct obstruction is typically attributed to the accumulation of ocular discharge within the lacrimal passages ; however , such cases may be more common , although they may go unrecognized . in the treatment of nasolacrimal duct obstruction , a bougie is normally inserted immediately after an irrigation test . because this blind insertion can be dangerous however , we believe that successful treatment is possible using only repeated irrigation with physiological saline . this approach is safe and simple , allows flushing of the entire lacrimal passage , and is effective in preventing recurrences . to perform this procedure , the physician should wait for the water to completely pass through during the irrigation test . then , instead of immediately inserting a bougie , irrigation should be patiently repeated numerous times . therefore , the irrigation should be considered not only as a test but also as a form of washout therapy . the patient reported here first presented with persistent lacrimation . only after repeated unsuccessful treatments was it determined to be due to obstruction by impacted foodstuffs . we have never observed any other cases in which a lump of foodstuff was retained in the nasolacrimal duct and caused an obstruction , as in the present patient . in other cases , the discharge contained in tears adhered to the lumen of the nasolacrimal duct and caused either narrowing or a state close to obstruction . therefore , such cases could be treated using flushing performed repeatedly to gradually wash out the discharge . this is not a frequent cause of nasolacrimal obstruction , but it should perhaps be considered as a possible factor in similar cases of refractory nasolacrimal disorders .

here we report a case of nasolacrimal obstruction resulting from rice grains ingested over many years that had formed an obstructive mass . this is a hitherto unreported cause of nasolacrimal obstruction . we exclusively treated the obstruction safely with repeated irrigation with physiological saline . although there have been various reports on new techniques such as the blind insertion of a bougie and insertion of a silicon tube under endoscopic guidance , successful treatment of this condition is possible with an old - fashioned approach using the time - honored tools of a syringe and an irrigation needle , if utilized patiently and repeatedly . in japan , we call this learning new lessons from the past. this implies that newer techniques may not necessarily be superior and traditional techniques can offer advantages of safety and simplicity in treating this condition .

rectal polypectomy causes thinning ( or even perforation ) of the rectal wall in addition to thermic injury at the polypectomy site . we present a rare case of spontaneous rectal perforation after uncomplicated nerve sparing endoscopic extraperitoneal radical prostatectomy in a patient with a previous history of rectal polypectomy at the perforation site . this conservative therapy for such rectal perforations is indicated if the patient 's general condition remains stable without any signs of infection . adequate time interval should be given to allow healing and avoid adding further thermal wall damage which may obscure healing leading to complications like fistula . conservative therapy for small missed rectal perforations constitutes an attractive , feasible and non invasive treatment entity . following this principle coloscopy is a routine examination for men over 50 years in germany . from the surgical point of view the other one is the perforation of the gut which is a severe and possibly lethal complication with a reported incidence of 0.1% to 0.9% [ 1 - 4 ] . most rectal injuries during nerve sparing endoscopic extraperitoneal radical prostatectomy ( nseerpe ) occur while transecting rectourethralis muscle cutting further into rectal wall . we present a rare case of spontaneous rectal perforation after uncomplicated nseerpe in a patient with a previous history of rectal polypectomy at the perforation site , which was successfully treated conservatively . in november 2005 , an otherwise healthy 71-year - old man with localised prostate cancer underwent nseerpe in our hospital . he gave history of polypectomy 10 cm from anus 4 weeks before , otherwise no clinical or laboratory abnormalities . coloscopy revealed bleeding from intraluminal wall laceration over a haematoma in polypectomy site ( figure 1a ) which was sealed with fibrin glue . ct revealed pelvic haematoma without detectable connections between rectum , bladder or abdomen ( figure 1b ) . ct at 16day showed established free connection between rectum and haematoma with some air without abdominal connections ( figure 2a , b ) . later , there was complete resorption of haematoma and healing of fistula as shown by abdominal ct ( figure 2c ) and coloscopy at 3month . psa is still undetectable . ( a ) rectoscopy view showing bleeding from wand haematoma without any fistula ( 2postoperative day ) . ( b ) ct examination showing pelvic haematoma without any signs of rectal perforation ( 3postoperative day ) . ( a. and b ) coronal and sagittal abdominal ct sections showing free connection between rectum and prostate bed with haematoma , contrast material and some air ( 16postoperative day ) . in this case rectal perforation could be either due to laceration because of previous polypectomy or missed iatrogenic perforation . owing to the intimate anatomical relation to prostate , it is our believe that this rectal wall thinning ( or perforations ) together with thermic injury at site of polypectomy should be given enough time to heal with adequate scare , otherwise it well predispose to laceration followed by perforation / necrosis in this site during or after operative manipulations . however care should be taken to exclude merely secondary haemorrhage due to clot dissolution in these cases which may manifest itself days to weeks after coloscopy ( 0.3 - 6.1% ) . although practiced in the beginning of open retropubic prostatectomy , most laparoscopic groups , including ours , leave the urethra intact during most of the dissection . instead , the plane between the seminal vesicles , prostate , and rectum is developed , progressing from the base of the prostate as close as possible to the apex . most of these injuries are visually identified intraoperatively and commonly repaired in a 2-layer suture with or without interposition of omentum / fat between the rectum and the vesicourethral anastomosis [ 5 - 7 ] . in case of missed perforations , signs and symptoms will be related to the size and site of the perforation , adequacy of bowel preparation , amount of peritoneal soilage , underlying bowel pathology ( e.g. thin walled colon from colitis or ischemia may result in a larger perforation than a healthy colon ) and finally , overall clinical condition of the patient . radiology often establishes the diagnosis however a localized perforation may demonstrate lack of pneumo peritoneum and necessitates other diagnostic procedures . management remains a controversial issue in that it can be effectively done by operative and nonoperative measures . generally , nonsurgical management is indicated if the patient 's general condition remains stable , the pneumoperitoneum does not increase in size , there are no signs of peritonitis and if the patient 's condition improves in response to conservative treatment . surgery is most definitely indicated in the presence of a large perforation , in the setting of generalized peritonitis or ongoing sepsis , the presence of concomitant pathology , unremitting colitis or perforation proximal to an obstructing distal lesion . finally , in the patient who deteriorates with conservative management . however , the best treatment for rectal injury during nseerpe remains prevention . although the primary reason is certainly anatomical since the plane of dissection is close to the rectum , another reason could be weakness of the rectal wall e.g. following polypectomy . in our opinion the later case needs 2 months in order to heal adequately and withstand operative manipulations . also to avoid adding further thermal wall damage to this site which may later obscure healing leading to more serious complications like fistula . according to this principle we have not faced this complication in following similar cases . nevertheless , the use of an intrarectal device / air should be emphasized in difficult cases due to surgeon inexperience , inflamed prostate , large volume gland , narrow and/or deep pelvis or previous rectal operations . these simple manoeuvres help in identifying the site of perforation and/or lacerations , if exist . about 2 months interval should be given to allow adequate healing before the operation and avoid adding further thermal wall damage which may obscure healing leading to complications like fistula . conservative therapy for these small missed rectal perforations constitutes a feasible and non invasive treatment entity . however in the presence of a large perforation , generalized peritonitis , ongoing sepsis or if the patient condition deteriorates surgery is indicated . intra - operative use of an intrarectal device / air should be emphasized in difficult cases . the authors disclose any commercial association that might pose a conflict in connection with the submitted article .

introductionrectal polypectomy causes thinning ( or even perforation ) of the rectal wall in addition to thermic injury at the polypectomy site.case reportwe present a rare case of spontaneous rectal perforation after uncomplicated nerve sparing endoscopic extraperitoneal radical prostatectomy in a patient with a previous history of rectal polypectomy at the perforation site . the patient could be treated conservatively . there was complete healing of the fistula without any effect on functional results . this conservative therapy for such rectal perforations is indicated if the patient 's general condition remains stable without any signs of infection.conclusionspolypectomy is an important risk factor for rectal perforation during nseerpe . adequate time interval should be given to allow healing and avoid adding further thermal wall damage which may obscure healing leading to complications like fistula . conservative therapy for small missed rectal perforations constitutes an attractive , feasible and non invasive treatment entity . following this principle we have not faced this complication in following similar cases .

four bat guano samples were collected from known roost sites on the remote offshore island of whenua hou ( codfish island ) ( 4647s , 16738e ) , which is situated at the southern coast of new zealand . it has special conservation status for the protection of endangered species , and public access is not permitted ( 9 ) . bat guano was held at 4c during transport ( < 48 h ) , resuspended in 2 ml phosphate - buffered saline , and subjected to centrifugation at 6,000 g for 5 min . rna was extracted from 400 l of supernatant by using the iprep purelink virus kit ( life technologies , carlsbad , ca , usa ) and eluted into 50 l reverse transcription pcr molecular - grade water ( ambion , austin , tx , usa ) . metagenomic sequencing was then conducted for 1 of the samples by using an illumina miseq instrument ( new zealand genomics ltd . , massey genome service , massey university , palmerston north , new zealand ) after a series of steps involving dnase i treatment , reverse transcription , multiple displacement amplification ( qiagen , valencia , ca , usa ) , and illumina truseq library preparation ( new zealand genomics , ltd . ) . a total of 10,749,878 paired - end sequence reads of 250 bp were generated and assembled into contigs by using velvet 1.2.07 ( 10 ) . assembled contigs were searched for viral sequence by comparison to the nonredundant nucleotide database in genbank ( downloaded march 2013 ) by using the nucleotide basic local alignment search tool ( national center for biotechnology information , bethesda , md , usa ) . forty - six contigs showed similarity to known genus alphacoronavirus sequences ( table ) . ( raw sequence data are available on request from the authors . ) * blastn , nucleotide basic local alignment search tool ( http://blast.ncbi.nlm.nih.gov/blast.cgi?program=blastn&page_type=blastsearch&link_loc=blasthome ) . virus sequence from the genus alphacoronavirus was confirmed in all 4 original guano samples by using a specific reverse transcription pcr based on the metagenomic data specific for 582 bp of the rna - dependent rna polymerase ( rdrp ) gene ( genbank accession nos . the rdrp sequence was identical in all 4 guano samples , and the closest relative was bat coronavirus hku8 ( genbank accession no . phylogenetic analysis was performed for rdrp ( figure 1 ) and for the spike protein , as derived from metagenomic data ( genbank accession no . we propose that these data support identification of a new alphacoronavirus , which has been designated as mystacina bat cov / new zealand/2013 . phylogenetic tree showing genetic relatedness of rna - dependent rna polymerase amino acid sequences for mystacina sp . bat coronavirus ( cov)/new zealand/2013 ( shown in boldface ) with those of known coronaviruses . evolutionary history was inferred for 183 informative amino acid sites by using the maximum - likelihood method based on the whilan and goldman model with gamma distribution in mega 5.05 software ( www.megasoftware.net ) . bootstrap values are calculated from 1,000 trees ( only bootstrap values > 50% are shown ) . tgev , transmissible gastroenteritis cov ; prcv , porcine respiratory cov ; sars , severe acute respiratory syndrome . bat coronavirus ( cov)/new zealand/2013 ( shown in boldface ) with those of known coronaviruses . evolutionary history was inferred for 492 informative amino acid sites by using the maximum - likelihood method based on the whilan and goldman + f model with gamma distribution and invariant sites in mega 5.05 software ( www.megasoftware.net ) . bootstrap values are calculated from 1,000 trees ( only bootstrap values > 50% are shown ) . tgev , transmissible gastroenteritis cov ; prcv , porcine respiratory cov ; sars , severe acute respiratory syndrome . the discovery of unknown coronaviruses provides information for a model of coronavirus evolution ( 11 ) and contributes to understanding the process of disease emergence , as in detection of middle east respiratory syndrome coronavirus ( 12 ) . the alphacoronavirus identified in this study from m. tuberculata bat guano is unique in respect to the extreme geographic and evolutionary isolation of the host bat species , which along with c. tuberculatus bats , has been separated from all other mammalian species for 1 million years . the current estimate for a common ancestor for all coronaviruses is 8,100 bce ( 13 ) . to be consistent with this estimate , mystacina bat coronavirus would need to have been introduced to bats on whenua hou within the past 800 years since humans first arrived on this island ( given that the island had no other mammals before this time ) ( 11 ) or is extant to modern alphacoronavirus phylogenetic radiation ( genesis and expansion ) . apart from humans , only 2 other terrestrial mammals have ever inhabited whenua hou : the brushtail possum ( trichosurus vulpecula ) and the polynesian rat ( rattus exulans ) , both of which were eliminated from the island in the late 1980s ( 11 ) ; neither mammal has been reported as a host of alphacoronaviruses . members of the genus alphacoronavirus infect only mammals . thus , an avian origin for this virus is unlikely . an alternative theory of an ancient origin for all coronaviruses has recently been proposed that involves an alternative evolutionary molecular clock analysis , which places the most recent common ancestor many millions of years ago ( 14 ) . the discovery of mystacina bat cov / new zealand/2013 virus could lend support to such a theory ; despite potentially millions of years of isolation , it has diverged relatively little from other extant alphacoronaviruses , as shown by the close relationship of the rdrp and spike protein genes to those of other extant alphacoronaviruses ( figures 1 , 2 ) . an expanded survey for mystacina bat coronavirus in mammals in new zealand and subsequent characterization of viral genomes would provide further insights into the origin of coronaviruses . only a small number of conservation staff handle these bats , these staff use standard personal protective equipment and work practice . staff are also offered prophylactic rabies vaccination as a precautionary measure , even though new zealand is free from rabies . the genus alphacoronavirus includes several human and animal pathogens , but on the basis of phylogenetic data in this study , it is not possible to estimate the risk posed by mystacina bat coronavirus to human or animal health . this country is free from many human and animal diseases , such as rabies and foot - and - mouth disease , and infections with human arboviruses because of recent colonization by humans and strict biosecurity border controls ( 15 ) . thus , indigenous wildlife in new zealand has generally been viewed as an almost sterile and unique biosphere . given detection of this coronavirus , more thorough characterization of the ecology of viruses and other microorganisms in native wildlife should be considered to fulfill conservation needs and further safeguard human and domestic animal health against cross - species transmission .

because of recent interest in bats as reservoirs of emerging diseases , we investigated the presence of viruses in mystacina tuberculata bats in new zealand . a novel alphacoronavirus sequence was detected in guano from roosts of m. tuberculata bats in pristine indigenous forest on a remote offshore island ( codfish island ) .

an inflammatory myofibroblastic tumor ( imt ) is a distinctive neoplasm composed of myofibroblastic and fibroblastic spindle cells accompanied by inflammatory infiltration of plasma cells , lymphocytes , and eosinophils . it is important to distinguish this tumor from other malignant spindle cell tumors , such as the sarcomatoid variant of urothelial carcinoma and leiomyosarcoma . we report a case of imt of the urinary bladder in a 52-year - old male diagnosed by transurethral resection of the bladder tumor ( turbt ) treated by partial cystectomy . his medical history revealed a diagnosis of rheumatoid arthritis 3 years ago , and prednisolone 10 mg / day was subsequently prescribed . cystoscopy revealed a solitary nonpapillary tumor with surrounding edema at the dome of the bladder ( fig . 1a ) . enhanced computed tomography ( ct ) and magnetic resonance imaging ( mri ) revealed an early enhancing bladder tumor infiltrating the outside of the bladder muscle layer ( fig . intraoperative findings showed a large solid bladder mass , measuring approximately 3 cm from the dome to the anterior wall of the bladder . we resected the tumor to the depth of the muscle layer , but normal muscle tissue was not seen . histopathology results were consistent with an imt . the bladder tissue , including muscle , was widely infiltrated by spindle cells in a myxoid stroma accompanied by infiltration of inflammatory cells ( fig . immunohistochemical staining was positive for vimentin and smooth muscle actin ( fig . 2c ) and negative for ae1/ae3 , desmin , myogenin , s-100 , cd34 , c - kit , cd68 , and bcl-2 . the excised specimen is shown in figure 2d . a pathological examination of the excised specimen revealed the proliferation of spindle cells expanding into the bladder musculature , accompanied by inflammatory cell infiltration . for the assessment of therapeutic options , we measured the expressions of anaplastic lymphoma kinase ( alk ) , vascular endothelial growth factor ( vegf ) , and cyclooxygenase 2 ( cox2 ) , known as growth factors involved in tumor proliferation . it is characterized by atypical spindle cell proliferation and inflammatory cell infiltrates primarily involving lymphocytes and plasma cells . although it has been associated with trauma , surgery , and infection , the majority of imt cases occur spontaneously . imt tumors are classified as intermediate ( rarely metastasizing ) tumors according to the who classification of soft tissue tumors . imts occur in the mesentery , omentum , retroperitoneum , pelvis , and abdominal soft tissues in 73% of cases . however , the occurrence of an imt in the urinary bladder is unusual . a systematic review by teoh et al . evaluated 182 imt cases and found a mean age of patients of 38.9 years , with a predilection for females . imts resemble malignant spindle cell tumors , such as sarcomatoid carcinoma , leiomyosarcoma , or rhabdomyosarcoma , making diagnosis difficult . recent reports have indicated that alk , which was originally identified as a protein overexpressed in anaplastic large - cell lymphomas , was also overexpressed in a substantial proportion of imts [ 5 , 6 ] . a positive finding of alk by immunohistochemistry in up to 87.5% of imts can be useful for the differentiation of imts from other spindle cell tumors . in this case , alk gene translocation in imts has also been reported , for which detection by fluorescence in situ hybridization ( fish ) is useful . however , performing fish in paraffin - embedded specimens is questionable for obtaining a precise diagnosis . alk protein expression , as determined by immunohistochemistry , correlates well with the presence of a rearrangement in the alk gene [ 7 , 8 ] . therefore , we did not undertaken fish analysis in this case because of the strong immunohistochemical positivity of alk . in the consideration of a therapy for imt , surgical resection , most patients underwent turbt ( 60.8% ) ; others had partial ( 29.2% ) and radical cystectomy ( 9.2% ) , and 5 patients experienced local recurrence . while partial or radical cystectomy ensures complete resection of imt , turbt is also a considerable choice , given the benign course of an imt . in the present case , ct , mri , and the examination of a turbt indicated a muscle layer - infiltrating lesion , so we performed a partial cystectomy . there were no reports as to the safety margin of imt in the bladder at partial cystectomy . we performed the operation by setting a margin of about 1 cm , and there was no sign of local recurrence in the bladder wall . for performing the operation while keeping the bladder capacity , further investigation as to the surgical margin cox2 and vegf expression have been detected in imts and are thought to be therapeutic targets . additionally , as an anti - inflammatory drug , cox2 inhibitors used for nonresectable imts have often been reported . an alk inhibitor , crizotinib , has also been used in the treatment of imts . in the present case , we examined cox2 , vegf , and alk protein expression with immunohistochemistry and found imt tissues to be vegf and alk positive . prednisolone has previously been prescribed in this case . we also thought that the tumor was resectable by partial cystectomy and therefore decided against a course of pharmacotherapy . however , in the case of recurrence when the tumor is not resectable , pharmacotherapy may become a viable therapeutic option . in conclusion , a typical imt can be locally aggressive and may require radical surgical resection ; close follow - up is therefore warranted . written informed consent was obtained from the patient for publication of this case report and accompanying images . a copy of the written informed consent is available for review from the editor - in - chief of this journal .

an inflammatory myofibroblastic tumor ( imt ) is a distinctive neoplasm composed of myofibroblastic and fibroblastic spindle cells , accompanied by inflammatory infiltration of plasma cells , lymphocytes , and eosinophils . imts rarely occur in the urinary bladder . it is important to distinguish this tumor from other malignant spindle cell tumors . herein , we report a patient with an imt showing muscle invasion , who underwent a transurethral resection of the bladder tumor and , at a later date , partial cystectomy . the resected tumor specimen revealed a proliferation of spindle - shaped cells on a background of plasma cells and lymphocytes . immunohistochemical staining showed the tumor to be positive for anaplastic lymphoma kinase ( alk ) , smooth muscle actin , and vascular endothelial growth factor ( vegf ) . such histopathological findings were indicative of an imt , suggesting the use of inhibitors of alk and vegf as pharmacotherapy .

psoriasis is a common , chronic , disfiguring , relapsing , inflammatory , and proliferative condition of the skin . long - term treatment of moderate - to - severe psoriasis is challenging and often requires a combination , rotational or sequential therapy , with two or more systemic agents . although it had been avoided earlier , combination therapy with methotrexate and cyclosporine is being increasingly found to be safe and useful in the management of psoriasis . we report here the case of a 57-year - old patient with unstable psoriasis , who developed unexpected methotrexate toxicity and cyclosporine - induced thrombocytosis in a span of two weeks of being given both drugs sequentially . we present this case to highlight the as - yet - unknown toxicities and interactions encountered with the administration of methotrexate and cyclosporine in the treatment of psoriasis . a 57-year - old male , who was known to be suffering from psoriasis vulgaris for the past 10 years , presented to us with features of unstable psoriasis for a duration of two weeks . he had been previously treated for multiple exacerbations with methotrexate ( cumulative dose - 2285 mg ) , cyclosporine , and topical steroids , on separate instances . he was a known diabetic for the past 10 years , on regular treatment with tablet metformin 500 mg twice a day . his baseline complete blood count showed leukocytosis ( leucocyte count - 18,300 cells / mm ; platelet count- 5 10/mm ) and the liver function tests were within normal limits . in view of the suspicion of unstable psoriasis , inj . after 24 hours , he developed multiple pustules over the nape of the neck and multiple oral erosions , resulting in severe odynophagia , with the existing lesions becoming more erythematous [ figure 1 ] . the hemogram showed a fall in the leukocyte counts ( 7,700 cells / mm ) . improvement in his blood count was also noted , as they returned to normal in four days ( leucocyte count - 9,700 cells / mm ; platelet count - 4.11 10/mm ) . the causality assessment , done using the naranjo algorithm , revealed a probable adverse drug reaction . mild erythema and hyperpigmentation of plaques three days after starting methotrexate and folinic acid following this , the patient was started on cyclosporine 100 mg , twice a day , to control the unstable psoriasis . one week after administration of cyclosporine , it was noticed that the platelet count increased three times from the baseline values ( 9.0 10/mm ) when tested , on multiple occasions . the platelet count dropped to a high normal value ( 5 10/mm ) four days after withdrawing the drug , thus confirming our suspicion . the naranjo scale scoring was 7 , which again implied a probable adverse drug reaction . the patient was then started on acitretin 50 mg once a day and was discharged after resolution of the lesions [ figure 2 ] . methotrexate and cyclosporine are considered to be the foremost treatment options of moderate - to - severe psoriasis . as both carry possible side effects and complications , factors predictive of methotrexate toxicity in patients with rheumatoid arthritis include absence of folate supplementation , high body mass index , prior gastrointestinal events , lower age group , female sex , renal impairment , change in dose , drug interactions , and infection . it remains unexplained as to why this patient , who had received methotrexate for many years , suddenly developed methotrexate toxicity after a relatively low dose . he was given a low dose of parenteral methotrexate , as he developed unstable psoriasis while on a low dose of oral methotrexate . the role of change of route of administration in causing methotrexate toxicity remains to be studied . an alternative explanation for thrombocytosis in our patient could be a reactive thrombocytosis set off by methotrexate toxicity or by the disease itself . however , the normal platelet count after withdrawal of cyclosporine is more suggestive of the former . reactive thrombocytosis is the exaggerated physiological response to a primary stimulus and is also known to accompany chronic inflammatory diseases like psoriasis . yasumoto et al . also reported reactive thrombocytosis in two patients with psoriasis , with associated raised il-6 ( interleukin-6 ) levels , thus supporting the theory that thrombocytosis could be caused by the disease per se . however , the fact that il-6 also has a role in the pathogenesis of psoriasis as t memory / effector cells that are chronically activated and poorly suppressed by regulatory t cells must be remembered . il-6 signals through stat3 and allows the escape of t memory / effector cells from t regulator - mediated suppression in a murine system . cyclosporine can induce il-1 expression in circulatory leukocytes and this may be sufficient to induce il-6 production in some tissues . this is a plausible explanation to the increase in platelet counts during cyclosporine therapy in our patient . the role of platelets in the inflammatory process is increasingly being recognized , in addition to their function in hemostasis and thrombosis . hence , the effect of the inflammatory process of unstable psoriasis on the platelet counts or vice versa is also an interesting postulate in our case ; the temporal course of events do not , however , suggest a correlation . we found it curious that our patient developed cyclosporine - induced - thrombocytosis a week after he recovered from unexplained methotrexate toxicity . there are no reports on similar hematological manifestations because of the potential interactions between methotrexate and cyclosporine when administered concurrently or sequentially . however , a study on the cytogenetic effect of methotrexate on human cells in vivo showed that methotrexate had a chromosome - breaking effect on human bone marrow cells . recent studies have highlighted that methotrexate and cyclosporine can be co - administered in patients with difficult - to - treat psoriasis . however , this case shows that there is still a need for caution , as late sequelae of long - term administration of the drugs are still unknown . we present this case to highlight that unknown long - term toxicities and unexplored interactions between systemic agents used for psoriasis still remain a chink in our therapeutic armamentarium for this common disease . this defect can be repaired by well - planned cohort studies and meticulous documentation of records of patients .

psoriasis is a common , chronic , disfiguring , inflammatory , and proliferative condition of the skin . it manifests with varying degrees of severity and can be treated with various immune modulators . this is a case report of a 57-year - old male patient of psoriasis on long - term oral methotrexate , who developed methotrexate toxicity when given an injection of methotrexate for unstable psoriasis . after recovery , the patient was started on cyclosporine 100 mg twice a day . after a week , he developed thrombocytosis , which reverted a week after cyclosporine was stopped . the patient is currently being managed with acitretin . the aim of this case report is to emphasize the various unpredictable adverse reactions encountered during treatment of psoriasis , especially when a combination or sequential treatment is used . there is a need for caution , as late sequelae of long - term administration of the systemic agents used in the treatment of psoriasis are still unknown .

hyper immunoglobulin e syndrome ( hies ) is a rare primary immunodeficiency disorder characterized by elevated serum ige , dermatitis , and recurrent skin and lung infections . three genetic etiologies of hyper ige have been identified : stat3 , dock8 , and tyk2 . association with tyk2 deficiency has shown some reported cases of hyper ige with disseminated nontuberculous mycobacterial ( ntm ) infection . microbial cultures of recurrent pulmonary infections show staphylococcus aureus , streptococcus pneumonia , and haemophilus influenzae more commonly while nontuberculous mycobacteria are secondary pathogens in pulmonary infections . tuberculosis ( tb ) has been rarely reported in children with hies with sporadic report of miliary tb . a 15-year - old boy who had been previously diagnosed to have hies in view of recurrent skin pustules with dermatitis and elevated serum ige ( ige = 3943 iu / ml [ normal = 10180 iu / ml ] ) along with skin biopsy suggestive of lymphomatoid papulosis presented with recurrent abdominal pain and fever 3 months ago . ultrasound ( usg ) of the abdomen showed multiple mesenteric lymphadenopathy , and mantoux test was positive ( 25 mm ) . he was started on four drugs for antituberculous therapy consisting of isoniazid ( h ) , rifampicin ( r ) , ethambutol ( e ) , and pyrazinamide ( z ) for 2 months and then hr as continuation phase . however , the child stopped antituberculosis treatment ( att ) after taking it only for 3 months . he then again had pain in the abdomen and presented to us for further management . on examination , his weight was 24 kg , height was 134 cm , and he had pallor and papular dermatitis all over the skin . on systemic examination , he had mild tenderness in the periumbilical region . investigations showed hemoglobin of 8.9 mg / dl , white blood cell count of 8100/cumm ( 58% polymorphs , 35% lymphocytes , 5% eosinophils , and 2% monocytes ) , erythrocyte sedimentation rate of 77 mm at the end of 1 h , and platelets of 238,000/cumm . usg of the abdomen showed multiple mesenteric lymph nodes with largest being 1.6 cm 1.4 cm . his urine showed albuminuria with microscopic hematuria . a repeat serum ige was elevated ( 8856 he was started on four drugs for att ( hrze ) , and urine was obtained for mycobacterium tuberculosis culture . natural human immunity to mycobacteria group relies on the functional interleukin-12/23-interferon - gamma integrity of macrophages connecting to t - lymphocytes / natural killer cells . patients with severe forms of primary immunodeficiency diseases have more profound immune defects involving this circuit , as seen in severe combined immunodeficiency , complete digeorge syndrome , x - linked hyper igm syndrome , cd40 deficiency , chronic granulomatous disease , and hies . a study shows that ntm infections are more common in hies patients with structural airway disease . in the absence of predisposing airway changes , ntm infections were not found in hies patients , suggesting that susceptibility to pulmonary ntm in hies may be more related to airway than immune dysfunction . an alternate explanation is the severity of immune dysfunction , through recurring infections , predisposes both to the severity of the structural lung disease and ntm disease . our patient was diagnosed to have abdominal tb based on the presence of mesenteric nodes , a positive mantoux test , and previous response to anti - tb therapy . we do not have bacteriological confirmation of tb as the lymph node biopsy was not undertaken in our patient . our patient did not have previous recurrent chest infections which could predispose to structural lung disease and thus he did not have pulmonary tb . the diagnosis of hies can be made based on a combination of clinical and laboratory findings for both types of hies . clinically , patients usually present with recurrent skin and lung infections , in the form of abscesses , dermatitis , or pneumonia . our patient had clinical features of skin involvement and elevated ige levels with recurrent skin infections suggestive of hies . we have not been able to do mutation analysis in our patient due to nonavailability of test . antibiotic prophylaxis with trimethoprim - sulfamethoxazole is frequently used as prophylaxis against recurrent respiratory infections . treatment of skin conditions such as eczema and skin infections is an important component of hies management . while there is no established guideline for the treatment of tb in primary immunodeficiencies , a case report of disseminated ntm in a patient with hies mentions that treatment with standard combination therapy for tb for a period of 12 months is indicated . another case report of miliary tb in hies was successfully treated with first - line att drugs . the role of interferon - gamma , granulocyte - colony stimulating factor , or other immune modulators in hies is unproven . bone marrow transplantation ( bmt ) is curative for autosomal - recessive hies with dock8 deficiency and it is recommended . autosomal - dominant hies patients do well with intensive therapy and supportive care , and bmt is not recommended for those individuals .

hyper immunoglobulin e syndrome ( hies ) is a rare primary immunodeficiency disorder characterized by elevated serum ige , dermatitis , and immunodeficiency that predisposes to multiple skin and lung infections . the most frequent pathogen responsible for infections in these patients is staphylococcus aureus . tuberculosis ( tb ) in patients with hies is an uncommon finding , and there are only a few reports of mycobacterial infections in known cases of hies . we present a case of abdominal tb that developed in a 15-year - old boy who also had hies .

a 30-year - old male patient received an above - elbow amputation about eight months prior to seeing us for an open fracture on the left radius and ulna due to trauma . he ended up transferring from one department to another department since his condition did not improve at all during treatment due to constant and severe pain after the amputation surgery . he kept complaining about cramping pain on his removed arm and electric - like pain occurring once every few minutes . he also said that he felt the entire shape of his removed arm , and it was medially rotated . every day , he was prescribed gabapentine ( 2,400 mg ) , oxycodon ( 200 mg ) , and amitriptyline ( 25 mg ) , with other medications to control the pain . however , the degree of his pain relief was somewhat insignificant and the visual analog scale ( vas ) was 8 - 10 out of 10 . other treatment methods , such as stellate ganglion block , thoracic sympathetic ganglion block , brachial plexus block , cervical transforaminal epidural block , and a subcutaneous infusion of ketamine , were also done . lastly , spinal cord stimulation ( scs ) was done for the patient , but the treatment effect was very insignificant . finally , we performed mirror therapy for the patient . he had to visit the hospital four times a week and went through a 15-minute treatment period . we had the patient feel the movement of his removed arm and hand just like his normal arm and hand moving through a mirror ( fig . after a week passed , the patient said that he could feel his medially rotated arm was back to normal , and his vas level decreased to 7 out of 10 . one month later , he said that the previous cramping pain was almost gone and the phantom hand and arm returned to normal . at that time , his vas level was 5 out of 10 . after , three month from the initial therapy , he is doing a mirror therapy three to four times a week at home . however , the electric like pain remains and the vas usually is maintained at 4 out of 10 . he is under follow - up at our outpatient department with oxycodon decreased to 100 mg a day . no treatment for phantom limb pain has yet been clearly proven in terms of its effect . drug therapy includes narcotic drugs , anti - epileptic medications , topical anesthesia , and analgesics . an infusion of ketamine , a n - methyl - d - aspartic acid receptor antagonist , was also introduced for phantom limb pain treatment . meanwhile , non - drug therapy includes sympathetic ganglion block , transforaminal epidural block , peripheral nerve block , transcutaneous electrical nerve stimulation ( tens ) , direct cortical or spinal cord stimulation , and mirror therapy , etc . mirror therapy was unveiled by ramachandran and rogers - ramachandran in 1996 . under this therapy , a patient is allowed to feel the imaginary movement of the removed body part behaving as normal body movement through a mirror . the mirror image of the normal body part helps reorganize and integrate the mismatch between proprioception and visual feedback of the removed body . rizzolatti used a mirror neuron to explain the fundamentals of a mirror therapy . at first , a mirror neuron was found in the monkey premotor cortex , and later , rossi discovered that humans also have similar mirror neurons systems . a mirror neuron fires both when a person acts and when a person observes the same action performed by another . then , the neuron mirrors the behavior of the other , as though the observer were itself acting . a mirror neuron provides observers with internally recognized experiences , making them understand other 's behaviors , intentions , and emotional status . therefore , while mimicking the behavior of the other , observers can experience not only the sensation , but also the similar emotion of the other . in this sense , a patient with phantom limb pain can feel the same sense or emotion of his / her normal body part by observing the mirror image . by doing so , it is expected to decrease pain by resolving conflict between motor intention , proprioception and visual system . a person without phantom limb pain and no amputations can not feel these sensory experiences since the signs from a non - mirror neuron block the mirror neuron , while a patient with an amputation does not have this non - mirror neuron system operating . the visual observation can help feeling empathy , which explains how the mirror therapy works for a patient . it is reported that the therapy is more effective on deep somatic pain ( e.g. , pressure sense and proprioceptive pain ) than on superficial pain ( e.g. , warmth sense and nociceptive pain ) . this is because deep tissues are responsible for integrating sensorimotor nerves as well as creating movements compared to superficial tissues . recently , mirror therapy has used for not only patients with phantom limb pain , but also for patients with complex regional pain syndrome and strokes . many studies indicate that mirror therapy is only effective for upper limb treatment , but it has potential as alternative treatment for pain that is difficult to control . in this study , mirror therapy resulted in dramatic pain relief for a patient with chronic phantom limb pain when other treatments such as medications , physical therapies , nerve blocks , nerve transformations did not work . mirror therapy is expected to be widely used for the treatment of phantom limb pain since it is easy to use at both home and in outpatient departments .

phantom limb pain is a painful sensation that is perceived in a body part that no longer exists . to control this pain , many methods have been used such as medication , physical treatment , nerve block , neuromodulation , surgical treatment and mirror therapy . however , until now , there effects have been uncertain . we report the successful reduction of phantom limb pain using mirror therapy when other treatments initially failed to control the pain .

an 18-year - old man was referred to our clinic for the evaluation of blurred vision involving the left eye that had manifested four days previous . he had no specific medical , ocular , or trauma history . the subject 's best - corrected visual acuity was 1.0 in the right eye and 0.9 in the left eye . vf ( central 10 - 2 sita - standard strategy ) was measured with a humphrey field analyzer ii ( zeiss - humphrey , san leandro , ca , usa ) under continuous monitoring . the oct demonstrated disruption in the photoreceptor inner and outer segment ( is / os ) junction and undulation of the rpe with backscattering ( fig . 2c ) , but the oct findings did not reveal improvement compared to the initial findings ( fig . the oct demonstrated a recovery of continuity in the photoreceptor is / os junction , as well as decreased rpe irregularity with minimal backscattering ( fig . arpe is an acute , transient , foveal disturbance of unknown cause and which affects young adults . because of scarce case reports and an infrequent prevalence of the disease , the diagnosis can be difficult without suspicion . fluorescein angiography ( fa ) is a critical test for the differential diagnosis of arpe . unfortunately , we could not obtain fa data because t he patient had signs of an anaphylactic reaction , such as dizziness and difficulty breathing , immediately after the fluorescein injection . therefore , we made a diagnosis based on the fundus findings in combination with the oct and other characteristics of the disease . white dot syndromes , especially multiple evanescent white dot syndromes ( mewds ) , should be considered in the differential diagnosis of arpe . white dot syndromes are characterized by multifocal white lesions and are accompanied by mild vitritis . mewds differs from arpe in that the lesions are located outside the macula in the posterior pole , and electroretinogram ( erg ) findings are abnormal . the main lesions responsible for mewds cause damage to the photoreceptor outer segment but not the rpe . in our case , there was a single white dot lesion that was limited to the juxtafoveal region ; also , erg , which was performed on the first visit , showed normal findings . in acute posterior multifocal placoid pigment epitheliopathy ( apmppe ) , multiple , large placoid lesions start in the posterior pole and extend to the post - equatorial fundus , often accompanied by prodromal flu - like symptoms . our patient 's lesions were discrete clusters of a few subtle , small grey spots that resolved without scarring within three months after onset . in contrast , the lesions in patients with apmppe are replaced by rpe changes upon resolution . the oct demonstrated rpe involvement , which was similar to the previously reported oct findings . based on these findings , other diseases were ruled out and the patient was diagnosed with arpe . hsu et al . first described the oct findings of patients with arpe using time domain oct ( oct3 ; carl zeiss ) as a hyper - reflectivity involving the outer nuclear layer , photoreceptor , and rpe . hyper - reflectivity has not yet been evaluated with sd - oct . in our case , we found a definite disruption in the is / os junction , as well as an undulation of the rpe according to sd - oct . because sd - oct can provide better image resolution than oct3 , we believe that the disruption of the is / os junction with sd - oct presented as a hyper - reflectivity of the outer retina with oct3 . as reported by hsu et al . , the thickness of the hyper - reflectivity decreased with increased resolution , and we found a decreased length of the is / os disruption based on the serial observations of the oct findings . the rpe irregularity also decreased as the symptoms improved and as the threshold of the visual field increased . on the basis of these findings , the morphologic changes in inflammation related to arpe do not seem to be permanent .

we investigated the case of a young man with blurred vision in his left eye . his visual acuity was slightly decreased , and ophthalmoscopy disclosed a gray - white lesion in the macula . he had no systemic or ocular history . on the visual field test , the threshold sensitivity was decreased in the corresponding region . spectral domain optical coherence tomography ( oct ) demonstrated a disruption in the photoreceptor inner and outer segment ( is / os ) junction and undulation of the retinal pigment epithelium ( rpe ) with backscattering . we re - examined the patient after two weeks and after three months without any treatment . visual acuity and visual field results were gradually normalized , and oct demonstrated the recovery of continuity in the photoreceptor is / os junction , as well as decreased rpe irregularity with minimal backscattering . we used spectral domain oct instead of time domain oct ( oct3 ) so that we could provide better image resolution of the acute retinal pigment epitheliitis ( arpe ) . finally , we observed recovery of the functional and anatomical changes in the arpe patient with a resolution of the condition within three months following the initial examination , using oct and visual field tests .

congenital maternal hyperplasia ( cah ) is a group of autosomal recessive disease in which dysfunction of one of the five cortisol coding genes occurs and causes enzymatic defects in cortisol synthesis cycle from cholesterol . the most common form of the disease is 21-hydroxilase deficiency , which accounts for 90 - 95% of the cah cases . in the 1950 s , it was found that there were a small group of patients that developed hypertension and responded to glucocorticoid . clinical manifestations of 11- - hydroxilase deficiency include , hypertension ( roughly occurs in 75% of patients and generally diagnosed during childhood ) and other signs related to overproduction of mineralocorticoids such as hypokalemia or muscle weakness , salt loss , and virilization . signs of androgen excessive secretion include early closure of the epiphysis ( short stature ) . the hypothalamic - pituitary - gonadal axis might cause amenorrhea or spermatogenesis disorders or hirsutism and acne . schmid type is an autosomal dominant skeletal dysplasia in which the commonest form is metaphyseal chondrodysplasia . the schmid metaphyseal chondrodysplasia is characterized by short stature , but bone maturation process is normal . however , bowed legs , coxa vara , and specific metaphyseal changes are seen on radiographs . in this article , we report a case of a 4-year - old boy with cah and schmid metaphyseal chondrodysplasia . our literature survey confirmed that it is the first reported case of coexistence of these two rare diseases . a 4-year - old boy with increased amount of pubic hair was referred to the children s endocrinology clinic . he was the first child of a family with normal growth and development until one year after birth . his parents were not related and there was no positive familial history . an increase in pubic and axillary hair developed four months later , he was treated for cah with 5 mg hydrocortisone , three times a day . another problem with this child was gait disorder and bowed knee ( figure 1 ) . there was a similar history with his cousin , considering that the cousin was affected by skeletal dysplasia . bowed knee in the patient with congenital adrenal hyperplasia . on clinical examination , doc level was 543 ( ng / ml ) and acth , dhea , 17-ohd , testosterone and androstenedione levels were higher than the normal limits . biochemistry tests such as bun , cr , na , p , k , and alkp were normal . laboratory test results radiological examination ( plain plantar view and knee radiography ) estimated the bone age to be about 10 years and 3 months . finally , the patient was treated for precocious puberty due to 11- - hydroxilase deficiency and schmid metaphyseal chondrodysplasia . after 5 months , testosterone level decreased to lower than 10 ng / dl and dhea reached 27 mcg / dl . schmid type metaphyseal chondrodysplasia is an autosomal dominant disorder and can be caused by various mutations in the col10a1 gene . its diagnosis is hard due to the rarity of the disease and its similarity to rickets , particularly vitamin d resistant type . however , rickets and schmid can be differentiated with normal bone density and irregular dense zone in schmid chondrodysplasia . in our case , schmid metaphyseal chondrodysplasia was considered by clinical manifestation and was confirmed with radiology and laboratory tests . bowed knee was the dominant characteristic sign and bone related biochemical tests such as ca , p and alkp were normal . the most important point in schmid disease is that over - treating by vitamin d , which can lead to toxicity , must be avoided . in some cases , congenital adrenal hyperplasias are a group of metabolic disorder diseases that lead to enzymatic defects in the biosynthesis of cortisol from cholesterol . clinical features of 11--hydroxylase deficiency in childhood might be premature pubarche and accelerated bone age , all of which occurred in our patient . the exact diagnosis of 11--hydroxylase deficiency can be performed by the high basal levels of deoxycorticosterone and or 11-deoxycortisol serums or tetra - hydrometabolites , which might be found during a 24-hour urine test . this disorder should be considered in patients with elevated serum levels of acth , about three times higher than the 95 percentile predicted for patient s age . its prevalence is 1 in 100,000 population and can be presented during childhood or adolescence . because of familial marriage in iran , cah incidence is high . according to a study by qaemi et al , rohani showed that precocious puberty could be a manifestation of non - classical form of cah and its early diagnosis and treatment is important . in some cases , . long - term complications of adrenal hyperplasia are short stature , infertility , gender identity disorders , and death . female neonates with ambiguous genitalia and male with precocious puberty are in the highest risk category to develop htn because of the high secretion of deoxycorticosterone ( doc ) . in our patient , mild htn was present . although cah can be associated with other genetic disorders , but this is the first report on the association between cah and schmid metaphyseal chondrodysplasia . 11--hydroxylase deficiency is a rare disorder and must be considered in patients with precocious puberty and secondly presented with hypertension .

congenital adrenal hyperplasia ( cah ) is a group of hereditary diseases , which are autosomal recessive . cah occurs due to defect in one of the cortisol coding genes and often clinically presents itself with signs of androgen overproduction . in this article , we report a case of cah and schmid metaphyseal dysplasia . our literature review indicated that this report is the first attempt on cyp11b1 and schmid dysplasia in a child . the specific diagnosis of 11--hydroxylase deficiency can be determined using high basal levels of deoxycorticosterone and/or 11-deoxycortisol serums .

biotinidase ( ec 3.5.1.12 ) is the enzyme responsible for cleaving biocytin and recycling biotin from dietary protein - bound sources , . profound biotinidase deficiency ( less than 10% of mean normal serum activity ) ( omim # 253260 ) is an autosomal recessively inherited metabolic disorder . untreated individuals with profound biotinidase deficiency usually exhibit neurological and cutaneous symptoms with metabolic acidosis and organic aciduria , . symptoms of the disorder can be markedly improved or prevented with pharmacological doses of oral biotin . however , if treatment is delayed , once vision or hearing problems or developmental delays occur , they are usually irreversible . all states in the united states and many countries screen their newborns for the disorder . the gene encoding biotinidase ( btd ) has been isolated and characterized , and over 150 mutations causing biotinidase deficiency have been identified . we now report the first microdeletion of btd that involves three of the four exons of the gene . this deletion further exemplifies the importance of performing microarray analysis or other methodologies for a deletion of btd when the enzymatic activity indicates lower activity than can be attributed to the mutations identified by dna sequencing . microarray analysis was performed by whole genome chromosome prenatal reveal snp microarray ( integrated genetics , labcorp specialty testing group ) . dna sequencing of the biotinidase ( btd ) gene was performed by pcr amplification using primers and conditions described previously . all exonic and intron - exon boundaries of the btd gene were sequenced by prevention genetics ( marshfield , wi ) . a non - consanguineous couple had prenatal diagnosis by microarray analysis for advanced maternal age . the results of the microarray analysis revealed a 26 kb interstitial microdeletion of chromosome 3p25.1 p25.1 ( arr { hg19 } 3p25.1 ( 15,674,11915,700,291 ) 1 . this heterozygous deletion is involves a major portion of the btd gene , including exons 24 ( fig . 1 ) . based on this information , it was important to determine if the baby had a mutation on the other allele causing biotinidase deficiency . to determine the likelihood that the baby had such a mutation , the parents had their serum biotinidase activities determined . the father 's activity was 5.5 nmol / min / dl ( range of normal activity is 5.7 to 8.7 nmol / min / dl ) and the mother 's activity was 2.9 nmol / min / dl . these results indicated that the father had normal activity and did not have a mutation of btd and the mother had activity in the heterozygous range . in fact , microarray analysis of the parents revealed that the mother did have the microdeletion . the fetal dna was sequenced and did not reveal any other mutations or variants . at birth , the infant did not have biotinidase deficiency on newborn screening ; however , the infant did not have serum enzymatic testing to confirm that her biotinidase activity was in the heterozygous range . we have previously reported a child with a contiguous gene deletion that involved three genes , including the btd gene . the child reported here is heterozygous for a microdeletion that only involves the btd gene . this deletion involves three of the four exons of the btd gene and is predicted to result in complete loss of biotinidase activity . this was confirmed by finding activity in the heterozygous range in the mother who also has the microdeletion . the reference laboratory that performed the microarray analysis indicates that they report deletions as small as 50 kb and they may report susceptibility genes when they are associated with clinical presentations that have a clear phenotype . however , many commercial laboratories that perform microarray analyses do not report microdeletions or duplications of less than 200 to 400 kb , unless the alteration involves a gene known to cause a dominant pathogenic disorder . in the instance reported here , the deletion is only 26 kb and an alteration of the involved gene , btd , which is only pathogenic as an autosomal recessive disorder . therefore , it is possible that some or most laboratories would have not reported this deletion , unless they were specifically performing testing for biotinidase deficiency . if , for example , an individual has biotinidase activity in the profoundly biotinidase deficient range and has a missense mutation on one allele and a deletion on the other , sequencing would have only identified the missense mutation . if this scenario occurs in an asymptomatic , profoundly enzyme deficient infant identified by newborn screening , it is imperative to reconcile the low enzymatic activity with finding only a single mutation . there are occasions when enzymatic activity is lower than expected from mutation analysis . in these cases , it is precisely for this reason we have recommended that confirmatory enzymatic activities be performed on the proband , parents and an unrelated control , . if there is confidence that the reduced enzymatic is not due to poor sample storage , then it is important to consider the possibility that a microdeletion is present on the second allele to explain the lower enzyme activity . it is important to consider microarray analysis for a possible deletion in children identified as having enzymatic activity on newborn screening consistent with profound biotinidase deficiency , but only are found to have a single mutation by btd sequencing . the possibility of a deletion involving part or all of the btd genes must be considered in those children having enzymatic deficiency that is inconsistent with the results of their mutation analysis .

we report the first microdeletion ( 26 kb ) of the biotinidase gene ( btd ) that involves three of the four exons of the gene . this deletion further exemplifies the importance of performing microarray analysis or other methodologies for a deletion of the btd gene when the enzymatic activity indicates lower activity than can be attributed to the mutations identified by dna sequencing .

in a recent issue of the new england journal of medicine , greet van den berghe and co - workers published a confirmation of the life - saving effects of tight glycaemia control by intensive insulin therapy ( iit ) in medical intensive care unit ( icu ) patients . this second study intended to answer some of the questions and criticisms raised by the landmark leuven study of 2001 , which reported a 4% decrease in mortality in a surgical icu population [ 2 - 7 ] . hopefully , these questions will be answered by the multi - centre assessments of the effects of iit , the nice - sugar and glucontrol trials , currently underway in australia and europe , respectively . before the completion of these two indispensable studies , greet van den berghe and colleagues wanted to confirm the life - saving effects of iit in medical icu patients in order to answer specific criticisms related to the type of patients , mostly surgical with two - thirds being post - cardiac surgery patients , in the first leuven study . indeed , patients with myocardial ischaemia could particularly benefit from a combination of a high amount of glucose and insulin , as reviewed recently . interestingly , krinsley reported a similar reduction in mortality in a mixed population of medical and surgical icu patients . greet van den berghe and colleagues succeeded but , as in most major contributions , their study raised more questions , which further argue for the importance of multi - centre trials . , this study can not be considered to be positive , as the long - stayers in whom a survival benefit was found were actually not randomised . the sample of long - stayer patients ( n = 767 ) was smaller than the calculated sample size of 1,200 patients that was required to test the working hypothesis ( a 7% reduction of the absolute risk of death ) with an alpha level of less than 0.05 and a beta level of 0.2 . in the entire set of patients , the intent - to - treat analysis indicated that there was actually no benefit related to iit . moreover , mortality in the patients in whom the stay was shorter than anticipated ( less than 3 days ) was higher in the iit group ( 26.8% ; 56/209 ) than in the conventional treatment group ( 18.8% ; 42/224 ) . this increase was found to be significant when analysed by the chi square test , but not by uncorrected proportional - hazards analysis , even after correcting for the difference in baseline risk factors . compared to the first leuven study , some of the recorded secondary end points that could be considered as surrogate markers of severity ( icu and 28-day mortality , requirement for dialysis , incidence of bacteraemia , requirement for prolonged antibiotic therapy , incidence of hyperbilirubinaemia and ' hyper - inflammation ' ) were not influenced as hospital mortality was . other local factors could also have influenced the results , thereby questioning the applicability of the findings to patients managed in other icus . the mean amount of parenteral glucose infused ( a mean of more than 220 g / day in long - stayers ) was probably higher than in most other icus , and parenteral steroids were used in more than half of the patients . unequivocally , these two factors reduce the risk of hypoglycaemia and the duration of episodes of hypoglycaemia , a major side effect of iit . nonetheless , the risk of hypoglycaemia was substantial , with 25.1% of the patients in the iit group experiencing a blood glucose level below 2.2 mmol / l ( 40 mg / dl ) at least once , compared to only 3.9% in the conventional group . the safety monitoring board of the german multi - centre study visep considered a similar increase in the incidence of hypoglycaemia important enough to stop this trial . clearly , the safety of iit needs to be assessed in patients with significant risk of hypoglycaemia . the target ranges of glycaemia were 4.4 to 6.1 mmol / l ( 80 to 110 mg / dl ) and 10 to 11 mmol / l ( 180 to 200 mg / dl ) , implying that there was no assessment of an intermediary blood glucose value , which is often used . greet van den berghe and colleagues already answered this question by analysing the data of the first study and concluded that there was a dose - response effect , with the largest improvement found in patients with the lowest blood glucose level . this hypothesis was found retrospectively , however , and clearly requires confirmation from prospective trials . the use of iit in leuven is probably easier than in other institutions with a lower nurse - to - patient ratio . for an iit approach , lastly , insulin exerts many effects other than a decrease in blood glucose , which could possibly be beneficial or deleterious in different subsets of patients ; these effects can not easily be assessed and monitored in the presently available trials . in summary , questions about the efficiency and safety of iit in different icus around the world are far from answered and much work has still to be done to answer the new questions raised by the second leuven study .

the second study on tight glycaemia control by intensive insulin therapy ( iit ) confirmed in medical intensive care unit patients the decrease in hospital mortality reported by the same team in the first iit trial in surgical patients . however , methodological concerns , the high rate of hypoglycaemia in spite of the infusion of large doses of parenteral glucose and the frequent use of steroids presently preclude considering these results as recommendations in other intensive care units , but rather argue for the need for large - scale assessment of the iit approach by multi - centre studies to confirm the efficacy and safety of this therapeutic modality .

to compare in - s and in - e among the three groups , the values were log - normally transformed to an approximately normal distribution before analysis , the geometric means ( gm ) and the geometric standard deviations ( gsd ) were calculated , and the steel rank sum test was applied . a single regression model and a single correlation analysis were used to evaluate the relationship between in - e and in - s . the mean age of the subjects was 38.5 years ( range 2063 ) , 87.5% were male , and 47.5% were current smokers . the mean duration of indium exposure was 8.2 years ( range 0.734.7 ) . in - e ranged from 0.004 to 24.0 g / m , and in - s ranged from 0.1 to 8.5 g / l . the gm ( gsd ) of in - e was 0.97 ( 8.68 ) in the smelting workers , 1.22 ( 2.19 ) in the ito workers and , 0.10 ( 6.49 ) in the other workers , respectively . the in - e values of the smelting workers and the ito workers were marginally ( p=0.0709 ) and significantly ( p=0.0069 ) higher than the in - e values of the other workers . the gm ( gsd ) of in - s was 0.93 ( 4.50 ) in the smelting workers , 0.58 ( 3.26 ) in the ito workers , and 0.12 ( 1.62 ) in the other workers , respectively . the in - s values of the smelting workers and the ito workers were significantly ( p=0.011 and 0.022 , respectively ) higher than those of the other workers . figure 1a shows a scattergram of log(in - e ) and log(in - s ) . the simple regression equation was log(in - s)=0.322log(in - e)0.443 , the regression coefficient was statistically significant ( p=0.0002 ) , and the simple correlation coefficient was 0.555 ( 95%ci 0.2900.741).fig . 1 . scattergram of log(in - e ) and log(in - s ) classified by job types.the x - axis represents log(in - e ) and the y - axis represents log(in - s).r : simple correlation coefficient . * : p<0.05 . scattergram of log(in - e ) and log(in - s ) classified by job types . the x - axis represents log(in - e ) and the y - axis represents log(in - s ) . because the distribution of the in - e and in - s values was different among the three groups , scattergrams were displayed for each group ( figs . the simple correlation coefficients were 0.489 ( 95%ci 0.4170.908 ) in the smelting workers ( fig . due to the small number of subjects , the distributions of the in - e and in - s values in the smelting and ito workers were not statistically significant , but they seemed to be linear ( fig . as far as we know , this is the first paper concerning the relationship between in - e and in - s . our research team has been interested in the relationship between in - e and in - s for a long time . however , we believed that it would be difficult to clarify this relationship because we believed that in - s may strongly reflect the amount of indium load in the lungs and , thus , the current in - s would not correlate to the current in - e . the reasons are supposed as follows : ( 1 ) due to the hardly soluble characteristics of indium compounds , the clearance rate of accumulated indium compounds in the lungs is very small7 ; ( 2 ) the in - s levels of formerly indium - exposed workers do not readily decrease4 and the biological half - life of in - s in formerly exposed workers who perfectly removed from indium exposure is around 8 years8 ; and ( 3 ) many indium processing plants have instituted labor hygiene management systems , and in - e and indium inhalation concentration may not be parallel due to the wearing of effective protective devices6 . in this study , we had a chance to measure in - s and in - e in 11 plants that had not yet taken action to improve the work environment . workers in these plants wore no or ineffective respiratory protective devices , and the in - e levels were expected to be low , so the indium load in the lungs of the workers could be expected to be small . however , it should be noted that extrapolation of this study s results to other indium - exposed populations requires careful consideration of whether the indium lung load in the population is actually negligible and whether the population wears appropriate respiratory protective devices . after the log transformation of in - s and in - e , this suggests that in - s may increase in - e - concentration - dependently in the workers in this study . figures 1b , 1c and 1d seem to suggest that the relationship between in - e and in - s may vary due to the chemical form of the indium compounds . ito , indium trioxide , indium metal , or indium alloy was the major chemical form in the ito workers , the smelting workers9 , and the other workers . though the number of workers was very small , in - e was correlated to in - s in the ito workers and in the smelting workers , but not in the other workers . we have no information about the difference in the kinetics of each chemical form in the lung , but indium metal or indium alloy may show different kinetics unlike ito or indium trioxide . first , the number of study subjects was not sufficiently large , and information of relatively high in - e levels was lacking . this may make it difficult to smoothly interpret the results , and indicates a need to expand the study . secondary , day - to - day variations of in - s are considered to be negligible , but day - to - day variations of in - e can not be ignored . we may need to measure in - e on multiple days . in conclusion , in - e and in - s seem to be positively correlated , but more data are needed to draw final conclusions . studies of the kinetics in the lungs of each indium chemical form are also necessary to elucidate the relationship between in - e and in - s . this study was supported by grants - in - aid for scientific research ( project no . 24590758 and 26860443 ) from the ministry of education , culture , sports , science and technology of japan ( 2012 - 13 and 2014 - 2015 ) .

the aim of this study was to assess the relationship between indium exposure concentration in the respirable dust fraction ( in - e ) and indium in serum ( in - s ) in workers . methods : a total of 39 workers were studied . the study subjects were categorized into 3 groups , namely , smelting workers ( n=7 ) , ito workers ( n=6 ) in an ito grinding plant , and other workers ( n=26 ) . in - e and in - s ranged from 0.00424.0 g / m3 and 0.18.50 g / l , respectively . the simple regression equation was log(in - s)=0.322log(in - e)0.443 . the simple correlation coefficients for the smelting workers , ito workers and other workers were 0.489 , 0.812 and 0.163 , respectively . the differences in the relationships among the three groups suggest that in - s may vary with the chemical form to which the workers were exposed . in - e and in - s seem to be positively correlated . the correlation coefficient was higher for both smelting and ito workers than for other workers .

for decades , urinary sodium ( nau ) was used to define the presence of structural damage to the kidneys in the setting of oliguria or azotemia . the preserved capacity of the tubules to retain sodium was the physiological basis to interpret low levels of nau as a functional response to a low renal perfusion state : socalled ' pre - renal ' azotemia . the loss of this capacity by the kidneys was considered a marker of ' acute tubular necrosis ' ( atn ) . in the past , levels of nau below 20 meq / l were considered markers of pre - renal impairment and above 40 meq / l as markers of intrinsic renal disease . recently , ' pre - renal ' and ' atn ' paradigms have been frequently criticized : first , because many cases classified as atn lack this finding in histopathological studies ; and , second , because increasing knowledge of acute kidney injury ( aki ) revealed a dissociation between renal hemodynamics and nau , especially in sepsis . therefore , these old paradigms gave place to a new paradigm : that nau is useless as a tool in aki management . the aim of this commentary is to question if this new paradigm should be sustained . in 2006 , a systematic review revealed that nau values were widely variable within and between studies with no consistent values to distinguish normal kidney function , pre - renal azotemia and atn . a contemporaneous experimental study inducing hyperdynamic sepsis revealed progressively lower levels of nau . it was hypothesized that the sodium retentive state was due to loss of glomerular filtration pressure . the authors concluded that nau was not a reliable marker of renal perfusion ( breaking the old ' pre - renal ' paradigm ) . since then , a new paradigm has emerged : nau must not be used as a diagnostic tool in aki . this phenomenon is the possible explanation for apparently paradoxical increases in the sublingual tissue partial pressure of carbon dioxide ( pslco2 ; a marker of microcirculatory stagnation ) in parallel with increasing cardiac output during sepsis . hence , a similar phenomenon could explain the paradox between an increased renal blood flow and low nau levels . glomerular perfusion pressure , not total renal blood flow , is the main determinant for nau levels . in inflammatory states , low glomerular perfusion pressure may occur in the presence of increased renal blood flow , with activation of sodium - retaining mechanisms . although tubular injury is an early event in aki , most studies still found low fractional excretion of sodium levels in this context . we may conclude that too much injury is needed to impair the global tubular capacity to retain sodium . recent unpublished results by our group also suggest that sodium retention is progressively more intense with increases in aki severity except in very advanced stages ( aki network stage 3 ) ; we hypothesize that extensive tubular injury jeopardized sodium reabsorption . in our findings , such progressive decreases in nau began earlier than increases in creatinine , as described in a case report . first , nau is measured only once instead of sequentially ; as previously demonstrated , nau responds fast to acute hemodynamic alterations so that relative alterations in it may be more relevant than an isolated nau value . it is important to remember that nau has a very large physiological range that depends on numerous variables . of these , the most likely responsible for an abrupt decrease in nau value is a decrease in glomerular filtration rate . second , nau is still treated as a categorical variable ; the dynamism of nau is lost if nau is viewed as ' < 20 meq / l ' or ' > 40 meq / l ' . third , nau is usually assessed only in the presence of oliguria or azotemia . in a recent article , we suggested that urinary electrolyte measurement may alert for the presence of aki development before increases in creatinine or oliguria . in that study , patients who developed aki in the first 4 days after admittance to the icu had significantly lower nau values at admission . low nau values in aki can be a sign of microcirculatory impairment in the kidneys . we have observed many critically ill patients with very low nau levels on the day that renal replacement therapy was initiated . this is not surprising in the context of multiple organ failure , which may be caused by systemic microcirculatory failure . from this perspective , the lower the nau , the greater the microcirculatory stress . on the other hand , including 10 healthy volunteers , the mean nau was 104 48 meq / l . meq / l at icu admission in patients who did not develop aki during the study period . however , high nau values can be found in patients with aki receiving diuretics or in advanced aki stages . as for many other monitoring parameters in critical care medicine , the first step in defining nau utility in daily practice is to understand properly what it is saying to us and in which contexts . aki : acute kidney injury ; atn : acute tubular necrosis ; nau : urinary sodium .

urinary sodium ( nau ) is one of the oldest parameters used in the evaluation of azotemia and oliguria . over the past years , however , it has progressively been considered as obsolete and useless , especially in sepsis . it is common sense that nau frequently does not correlate well with global renal blood flow . if intrarenal microcirculatory changes are more important in acute kidney injury ( aki ) than changes in global renal blood flow , we speculate that decreases in nau may be viewed as a possible marker of microcirculatory impairment in the kidneys . recent findings by our group ( some not yet published ) in which sodium retentive capacity is preserved until advanced stages of aki and the observation of decreases in nau preceding increases in creatinine bring us to conclude that the new paradigm of abolishing nau consideration from daily approaches to managing patients at risk for aki must be reevaluated .

seroprevalence of hydatidosis is between 1.2 and 13.8% in the different region of iran ( 1 ) . brain involvement occurs in 12% of patients with hydatidosis and comprises 2% of all brain masses in the endemic region , especially among the children ( 2 ) . symptoms of the brain hydatid cyst vary by location and size of the cyst . in a retrospective study of 117 children in tunis , common symptoms were a headache , vomiting , hemiparesis , seizure , mood alteration , and skull deformity ( 3 ) . more than 50% of patients with the brain hydatid cyst have multiple cysts in the brain , and about 18% have visceral involvement , which has 9% mortality rate ( 4 ) . surgical treatment and excision of the cyst ruptures of the cyst and anaphylactic reaction are the most frequent complication of the surgery with the prevalence of 10% . here we present an adult male with a large brain hydatidosis and atypical symptoms , who was treated successfully by surgery . a 19 yr - old male livings in ardabil , northwest of iran , was referred to neurosurgery clinic in khanevadeh university hospital , tehran , iran for a headache and progressive left hemiparesis since a week ago . he was treating for depression and incuriosity for two months by a psychologist . during two weeks , he developed headache , vomiting , and in the last week , left - side paraparesis occurred . peripheral neurological examination showed left hemiparesis with the force of three to fifth in all muscle groups and normal deep tendon reflexes . brain contrast - enhancing magnetic resonance imaging ( mri ) showed a large round mass about eight centimeters in the right frontoparietal lobe and mildly shifting the cerebral hemisphere to the left , without any ring - enhancement or surrounding edema ( fig . 1 ) . contrast - enhanced t1-weighted brain mri shows a large brain hydatic cyst in the right frontoparietal lobe with mildly shifting of the cerebral hemisphere laboratory results showed mild anemia ( hemoglobin=13.1 milligrams per deciliter ) . further laboratory and imaging findings were normal , except for antibody titer against echinococcosis , which raised fourfold above - normal range in igg . oral treatment with albendazole at a dose of 400 mg twice daily was initiated , and the patient underwent surgical excision of the cyst . right craniotomy through parietal bone with left side , head turning position was done under general anesthesia . a largely fluctuated mass with adhesion to surrounding tissue appeared after dural opening , and 3% warm saline infused around the mass during 30 min , which led to slowing delivery of the mass in the next 40 min ( fig . 2 ) . surgical excision of the brain hydatic cyst via right craniotomy through parietal bone finally , free layers were sutured anatomically consequence , and the bone fixed by bone - adhesive glue . oral treatment continued about three months . after one - yr follow - up , left hemiparesis improved , and the left side limbs forces raised to four - fifths . at this time brain mri cystic hydatid disease ( chd ) is an infectious parasitic disease , often caused by e. granulosus . this parasite distributes worldwide , and the main routes of transmission are ingestion of foods or water , which is contaminated by scolex or egg . 12% of the patients have cerebral involvement , especially in the parietal lobe ( 2 ) . brain hydatid cysts may grow up 110 cm a year and symptoms are often related to elevated intracranial pressure ( icp ) and focal neurological deficit ( 5 ) . in our patient , symptoms of rising icp appeared in the advanced course of the disease and the main complaints , which resulted in seeking medication , were depressive mood alteration , personality instability , and apathy . dowling technique is often used for surgical excision , which consists of craniotomy through a big opening hole , cortical dissection and hydrostatically delivery of the cyst using an injection of hypertonic saline ( 3 ) , such as our patient . ruptures of the cyst and anaphylactic reactions are the most common complication of the surgery , but other complications such as subdural effusion , hematoma , pneumocephalus or herniation must be considered ( 6 ) . emergent brain surgery was performed in a 13 yr - old male for cerebral herniation because of a massive brain hydatid cyst ( 5 ) . despite the significant size of the cyst and adhesion to surrounding tissue in our patient , he did not experience any complication . it seems that other related factors such as adhesion to surrounding tissue , the severity of intracranial pressure , access to the operative field , and expertness of the surgeon may influence the outcome . we believe that the best surgical technique for excision of the cyst is adequate craniotomy , gentle decortication and enough time spending during the surgery .

brain hydatid cyst constitutes one of the leading causes of cranial mass in the endemic region , especially among the children . symptoms of the disease are associated with rising of intracranial pressure and focal neurological deficit . surgical excision of the cyst is essential to treatment . here we present a 19 yr - old male livings in ardabil , northwest of iran , referred to neurosurgery clinic in khanevadeh university hospital , tehran , iran with a large brain hydatid cyst and atypical symptoms . he was treated by surgical excision of the cyst without any complication . there were not any clinical or radiological signs of recurrence after one - year follow - up .

briefly , we retrospectively reviewed adult mdr tb and xdr tb patients admitted during 20032008 for treatment initiation to king george v hospital ( kgvh ) , a public tb - referral hospital in kwazulu - natal . admitting physicians and staff collected data routinely . during the study period , kgvh was the only public hospital in the province authorized to initiate treatment for mdr tb and xdr tb , and all therapy was initiated on an inpatient basis . all patients > 18 years of age who had culture - confirmed mdr tb or xdr tb with standard drug susceptibility testing were included . ethics review committees at the university of kwazulu - natal and boston university ( boston , ma , usa ) approved the study protocol . univariate and multivariate logistic regression models were used to estimate odds ratios ( ors ) and 95% confidence intervals ( cis ) . statistically significant variables or variables that caused > 10% change in the univariate or were included in the multivariate model . a total of 4,941 patients with mdr tb or xdr tb from throughout kwazulu - natal were admitted for initiation of drug - resistant tb treatment to kgvh during the study period ( figure ) . among 4,514 eligible patients with mdr tb or xdr tb , women were younger ( median age [ interquartile range ] 32 [ 2639 ] vs. 36 [ 3044 ] years ) , more likely to be hiv infected ( 65% vs. 47% ) , and more likely than men to be receiving antiretroviral therapy ( art ) ( 51% vs. 43% ) ( table 1 ) . women with drug - resistant tb were more likely than men with drug - resistant tb to have xdr tb ( p<0.0001 ) . flow diagram for patients with multidrug - resistant ( mdr ) and extensively drug - resistant ( xdr ) tuberculosis ( tb ) admitted to king george v hospital , kwazulu - natal , south africa , 20032008 . * mdr , multidrug - resistant ; tb , tuberculosis ; xdr , extensively drug - resistant ; art , antiretroviral therapy . median patient age ( interquartile range ) : women , 32 y ( 2639 y ) ; men , 36 y ( 3044 y ) ; p<0.0001 . on univariate analysis , hiv status , art ( among hiv - infected ) , female gender , previous tb treatment , and year of admission to kgvh were significantly associated with xdr tb ( table 2 ) . on multivariate analysis , only female gender ( or 1.38 , 95% ci 1.111.73 ) , previous tb treatment ( or 2.16 , 95% ci 1.094.28 ) , and year of admission were independently associated with xdr tb . in the hiv strata , art was not significantly associated with xdr tb after adjustment was made for confounding variables . confounding of art and xdr tb by year of admission among hiv co - infected persons most likely resulted from increased xdr tb case finding after a highly publicized xdr tb outbreak in 2006 and increased art use after public health rollout of art in kwazulu - natal in 2004 . the interaction terms hiv gender , gender age ( categorical ) , and health care worker ( hcw ) gender were not significantly associated with xdr tb . * xdr , extensively drug - resistant ; tb , tuberculosis ; mdr , multidrug - resistant ; or , odds ratio ; ci , confidence interval ; art , antiretroviral therapy . median age ( interquartile range ) : mdr tb patients 34 y ( 2842 y ) ; xdr tb patients , 35 y ( 2942 y ) . most ( 59% ) patients admitted with xdr tb were women , which did not change significantly during the study period ( test for trend p = 0.68 ) . for mdr tb , the data showed increasingly more female mdr tb patients admitted over the study period ( p<0.001 ) ( table a1 ) . our major finding was that women admitted with drug - resistant tb to kgvh were 38% more likely than men to have xdr tb . temporal analysis showed persistently more women with xdr tb and increasing proportions of women with mdr tb during the study period . together these data support the notion that the epidemic of drug - resistant tb predominantly affects women in kwazulu - natal . supporting context comes from observational studies of drug - resistant tb in south africa . in south african studies , higher percentages of xdr tb ( 50%56% ) than mdr tb patients ( 43%53% ) are women ( 69 ) . however , studies from low - prevalence hiv settings report fewer women with drug - resistant tb . in a study in the united states , few patients with mdr tb ( 36% ) or xdr tb ( 38% ) were female ( 11 ) . similarly , in cohorts from latvia , peru , and russia , lower percentages of patients with mdr tb ( 17%40% ) and xdr tb ( 29%35% ) were female ( 1214 ) . gender differences in drug - resistant tb in areas of hiv endemicity and low prevalence suggest a possible effect of the aids epidemic on prevalence of drug - resistant tb in women . women with xdr tb might have been preferentially referred compared with men with xdr tb , women with mdr tb , or both . we lacked data on hiv factors , such as cd4 t - cell counts , art adherence , and viral load . similarly , we lacked data on previous tb treatment , medications , adherence , and outcome . finally , as a hospital - based retrospective study , factors associated with survival to hospital admission , decisions to seek care , and referral patterns may introduce bias . for example , women with drug - resistant tb may be more adherent to art , leading to improved survival , and therefore increased time for xdr tb to develop . factors associated with secondary development of xdr tb , such as tb medication adherence or previous mdr tb treatment , could explain the association between xdr tb and female gender ( 15 ) . factors associated with exposure to drug - resistant tb strains , including location and duration of exposure , could explain the association of xdr tb and female gender . for example , women are more likely to participate in formal and informal care work , with potential exposure to drug - resistant tb strains , and therefore primary xdr tb might be more likely to develop ( 5 ) . these results may have major policy implications for tb control in kwazulu - natal and south africa . because women are more likely to have xdr tb in kwazulu - natal , efforts should be made to develop gender - sensitive interventions to improve diagnosis , treatment , and prevention for drug - resistant tb and hiv . decentralization of drug - resistant tb treatment may better accommodate women in conjunction with their work , family , and child - rearing responsibilities . further studies are needed to confirm the magnitude and determinants of the association between female gender and xdr tb .

to determine whether women in kwazulu - natal , south africa , with drug - resistant tuberculosis ( tb ) were more likely than men to have extensively drug - resistant tb , we reviewed 4,514 adults admitted during 20032008 for drug - resistant tb . female sex independently predicted extensively drug - resistant tb , even after we controlled for hiv infection . this association needs further study .

we analysed data from the czech part of the hapiee project ( peasey et al . the study recruited over 8000 caucasian men and women aged 4569 years at baseline ( 20022005 ) , randomly sampled from population registers of seven czech towns . dna was extracted from venous blood samples and apoe genotypes were determined using the conventional pcr - rflp method ( hixson & vernier , 1990 ) . two criteria were adopted to define hand dominance , both using data collected during the re - examination of the cohort in 20062008 ( total of 5362 participants ) . second , we used grip strength data and classified as left - handed those who recorded higher grip strength on their left hand on both successive tests . both hand dominance and apoe genotype were available for 4438 participants ( 2022 males and 2416 females ) , mean age 58.0 ( sd 7.1 ) years . differences in the proportion of left - handed individuals between apoe subgroups , both in the full sample and when stratified by age and sex , were assessed by a chi - square test . in addition we tested the association between left - handedness and the presence of the apoe2 allele vs either apoe33 or 43/44 , using logistic regression . we also assessed the association separately by 5-year age group , and we tested for potential interaction between age group and apoe genotype . all analyses were conducted using the stata version 12 statistical software ( station college , tx , usa ) . the study was approved by the local ethics committees at both czech national institute of public health and at university college london . a total of 217 ( 4.9% ) individuals reported having a dominant left hand for writing and 543 ( 12.2% ) persons had consistently higher grip strength on their left hand . these two measures were strongly correlated ; individuals with higher left hand grip strength were five times more likely to be self - reported left - handers ( odds ratio 5.2 , 95% confidence interval 4.06.7 , p < .0001 ) . the frequency of the most common apoe3 allele was 81.1% , followed by the apoe4 allele ( 11.3% ) , and the least common was the apoe2 allele ( 7.5% ) . the distribution of left - handers based on either self - report or grip strength did not differ between carriers of different apoe genotypes ; the p - values were 0.828 ( 2.1 , 5 df ) and 0.557 ( 3.9 , 5 df ) ( table 1 ) . similarly , there were no statistically significant differences when carriers of apoe2e2 and apoe2e3 were combined , and compared with apoe3e3 homozygotes and with apoe4 ( apoe4e3 and apoe4e4 ) carriers , with no odds ratio being anywhere close of statistical significance ( table 2 ) . distribution of left - handers among the different apoe genotypes age - sex - adjusted and age - specific odds ratios of left - handedness by presence of apoe2 allele , with confidence intervals and p - values . left - handedness was the dependent variables coded as 0 ( non - left - handed ) and 1 ( left - handed ) ; the presence of apoe2 allele was coded as 0 ( no apoe2 allele present ) and 1 ( at least one apoe2 allele present ) . adjusted for age and sex further analyses , stratified by 5-year age group , did not reveal any significant association between left - handedness and apoe genotype in any age group , nor any interactions between apoe and age group ( table 2 ) . similar analyses , stratified for sex , also produced negative results ( table 2 ) . while many studies have suggested a genetic contribution to handedness ( see annet , 1994 ) , very few studies investigated specific genetic markers in relation to left-/right - handedness ( scerri et al . this study , a study of children , did find an association between apoe and left handedness ( bloss et al . , 2010 ) . our study , much larger than the previous investigation but in adults , did not find any association between apoe genotype and hand dominance . the apoe genotype frequencies in our study were similar to the frequencies detected in neighbouring populations ( bazrgar et al . 2008 ; gerdes , klausen , sihn , & faergeman , 1992 ) ; they also did not differ significantly from the study by bloss et al . the genotype frequencies were also similar to a study conducted in neighbouring slavonic / polish population in which the apoe4 allele was associated with elevated risk of alzheimer disease ( klimkowicz - mrowiec et al . , 2010 ) . there are two main limitations of our study : the measurement of handedness and the restricted age range of the examined individuals . both these factors limited our ability to analyse life - long handedness and possible redirection of handedness in childhood . hand preference is more a continuous rather than binary trait , and ambidexterity may be more common than strict left - handedness ( llaurens et al . , the assessment of handedness in our study was based on subjective self - report and on measurement of grip strength , not allowing to us to detect the potential ambidextrous individuals . none of our two outcome classifications is ideal , especially because the age groups included in our study might have been forced to use their right hand when they were children . this fact may also explain the discrepancy between self - report and grip strength results , although in both methods the proportions of left - handers were reasonably close to the expected range of 5 to 10% ( llaurens et al . , 2009 ) . on the other hand one might argue that the degree of enforcement might have differed between sexes or between birth cohorts ; the absence of any confounding or effect modification by age or sex contradicts the presence of a major bias . the observations that the proportion of left - handed persons based on grip strength was close to prevalence of 12% reported in an earlier study in the czech population ( dvorakova , & zvolsky , 1989 ) , and the expected higher prevalence in males than females , further suggest that the grip strength based measure may be the more reliable of the two measures . our study had sufficient power to detect relatively modest differences in the prevalence of left - handedness between apoe2 carriers and carriers of others genotypes , and the three - fold difference reported by bloss et al . however , we can not completely exclude the possibility that small differences exist in left - handedness and apoe genotypes . given the low prevalence of apoe2e2 and apoe4e4 homozygosity ( less than 1% ) , a much larger study would be needed to demonstrate such a small effect for these rare genotypes . notwithstanding these limitations , there was no suggestion of an association between apoe genotype and left - handedness . ( in press ) . we therefore conclude that common polymorphism within the apoe gene is likely not a major genetic determinant of left - handedness in adults .

an association between apoe genotype and left - handedness has been previously reported . we examined whether such association exists in a population sample of 4438 unrelated caucasian adults aged 4569 years ( 2022 males and 2416 females ) . left - handedness was based on self - reported left - hand dominance for writing ( prevalence 4.9% ) and on consistently higher left - hand grip strength in two repeated measurements ( prevalence 12.2% ) . individuals with higher left hand grip strength were seven times more likely to be self - reported left handers ( p < .0001 , 2 159.7,2 df ) . there were no differences in the proportion of self - reported left - handedness ( p = .828 , 2 2.1 , 5df ) or higher grip strength in left hand ( p = .557 , 2 3.9 , 5 df ) between apoe genotypes . the lack of association was similar in both genders and did not differ by age group . the results suggest that left - handedness in adults is not related to apoe genotype .

diaphyseal aclasis , also termed hereditary multiple exostosis ( hme ) or osteochondromatosis is characterised by multiple bony prominences that grow near joint lines throughout the skeleton . these bony prominences , otherwise known as exostoses , can present as painless bony deformities or as a complication of the bony growth . ( 1 ) there have been approximately 100 cases in the literature of vascular complications due to osteochondromas including pseudoaneurysm formation , occlusion , rupture or thrombosis . ( 2 ) this article describes the case of a 15 year old boy , with known hme , referred to the sarcoma mdt with a 9.5 cm diameter mass in the popliteal fossa , confirmed by ultrasound as a delayed presentation of a pseudoaneurysm . a 15-year - old boy , with diaphyseal aclasis , presented with a two month history of a painful swelling in his left popliteal fossa , reportedly increasing in size . he presented to his local orthopaedic department where repeated radiographs ( figure 1 ) illustrated decreased cortical definition of the exostosis arising from the medial femoral metaphysis 15 cm above the knee joint . at this point he was referred to the regional sarcoma mdt due to concern that the lesion had undergone malignant transformation . plain radiographs of the patient s left knee on examination , there was a 10 cm , non - tender , pulsatile mass in the popliteal fossa . the foot was warm with normal capillary refill , palpable posterior tibialis artery but absent dorsalis pedis . the mri scan showed a lesion measuring 9.5 cm in its greatest diameter , of uniform signal , with a cartilage cap exceeding 2 cm throughout most of its surface . ( figure 2 ) mri scan of the patient s left leg an ultrasound concluded an 8.8 cm pseudoaneurysm and the patient was admitted for urgent pre - op ct angio ( figure 3 and 4 ) and surgical exploration . ct angiogram 3d reconstruction- showing the bony exostoses and the popliteal aneurysm posterior to the right distal femur ct angiogram : showing the diameter size of the aneurysm to be 88.6 mm . the cross sectional image clearly shows the sharp bony exostoses that slowly eroded into the popliteal artery resulting in the pseudoaneurysm formation . the image also shows that the defect in the artery is still patent because the pseudoaneurysm is filling with contrast the popliteal artery was explored . ( figure 5 ) the proximal popliteal artery was found to have a 1 cm x 0.5 cm wall defect adjacent to the bony exostosis . ( figure 6)the exostosis was excised and the 4 cm of diseased artery repaired with end - to - end interpositional long saphenous vein graft . ( figure 7 ) intraoperative photograph showing the popliteal aneurysm intraoperative photograph showing the 1 cm x 0.5 cm defect in the popliteal artery wall caused by the sharp bony exostoses intraoperative photograph showing the end to end interpositional long saphenous vein graft post operatively the patient recovered without complication . he was followed up with an ultrasound doppler after 6 weeks demonstrating a patent vein graft and will undergo local vascular follow - up . his 6 month post - operative check - up revealed no complications but he will have regular follow - up for any painful , rapidly growing exostosis associated with his hereditary condition . diaphyseal aclasis is a rare genetic skeletal condition due to developmental abnormalities of the growth plate causing multiple cartilage covered exostoses to form on the surface of the metaphysis or the adjacent diaphysis region of long bones . diaphyseal aclasis is usually diagnosed in childhood however it is believed that radiologically the exostoses are present since birth . ( 3 ) vascular complications of the popliteal vessel occur due to ossification of the previously protective cartilage cap , around the 2 decade and relative immobility of the artery in the popliteal fossa between exiting hunter s canal and the trifurcation . ( 4 ) the artery undergoes chronic abrasion on the sharp exostosis forming a defect in the adventitia resulting in pseudoaneurysm formation . ( 5 ) it is controversial whether exostoses that lie near a vascular axis should be removed on identification to prevent vascular compromise from occurring . considering most exostoses are innocent , most authors suggest that surgical excision is only required when complications have occurred or malignant transformation is suspected . if preventative surgery is not performed , regular ultrasound doppler scans should be performed in order to screen for complications . ( 6 ) in addition to vascular complications , bony exostosis can also present acutely with nerve compression , bursitis due to bony irritation , stalk fracture or necrosis of the cartilaginous cap following infarction . ( 7 ) due to the acute presentation of this vascular complication there was no time for pre - operative tissue diagnosis , which would be routinely performed . it was important that the procedure was performed by an experienced orthopaedic tumour surgeon to ensure adequate margins were achieved . recent studies report a lifetime risk of sarcomatous transformation in single lesions of approximately 1% but up to 5% in hme . ( 8) the majority are chondrosarcomas , however , osteosarcomas and malignant fibrous histiocytomas have been reported . concerning features that warrant further investigation include : a rapidly enlarging mass , particularly in those beyond skeletal maturityshoulder girdle and pelvic exostosis ( 9)cartilage capsule exceeding 1.5 cm a rapidly enlarging mass , particularly in those beyond skeletal maturity shoulder girdle and pelvic exostosis ( 9 ) cartilage capsule exceeding 1.5 cm investigation with ultrasound , mri and image guided or open biopsy is advocated if an exostosis has concerning features . there are recent studies advocating pet / ct imaging to monitor known benign exostosis for malignant transformation . ( 10 ) due to the relative rarity of these lesions it is important to review the images and histology in a specialised bone tumour multi - disciplinary meeting . this case illustrates a late presentation of a known complication associated with diaphseal aclasis . in this age group we present one of the largest , non - ruptured , popliteal pseudo aneurysms reported . it is important to maintain a high index of suspicion of an increasing soft tissue lesion due to the risk of sarcomatous transformation in patients with mhe ; however , this focus delayed earlier presentation to vascular surgeons putting the patient at risk of a limb threatening rupture .

a 15 year old boy , with known diaphyseal aclasis , presented with a swollen left leg . the diagnosis of popliteal pseudoaneurysm , a known and well understood vascular complication , was delayed due to presentation suggestive of a chondrosarcoma . in this age group , sarcomatous change is more common and a potentially sinister complication of diaphyseal aclasis . following a sarcoma mdt referral , the correct diagnosis was confirmed by ultrasound and ct angiogram . this case identifies one of the largest , non - ruptured popliteal pseudoaneurysms reported and illustrates an unusual complication of a rare orthopaedic genetic condition , which is potentially limb threatening .

the problem of finger in the patient with diabetes mellitus is important consideration in diabetology . generally , peripheral neuropathy that manifests with finger paresthesia , numbness , and blanching is common . nerve conduction studies , vibration and temperature threshold measurements , and neurovascular function tests are useful for assessment of these cases . however , some recent reports mention the concern on trigger digits in diabetic patients . in this brief article , the authors focus review and discussion on this specific topic . indeed , trigger digits can be seen in any population . however , some recent publications report on the importance of this disease in diabetes mellitus . the incidence of trigger digits was about four times higher than in the general population . the trigger digits can be seen in 1:20 ( cases with trigger digits : all diabetic patients ) . however , some other reports such as that by aydeniz et al . show no significant increase in the incidence of this condition in diabetic patients . it is concluded that the trigger digits are an important problem for the diabetic patients . screening for diabetes may be warranted in patients with involvement of more than three digits . the summary of the important publications reporting on the prevalence of the problem can be seen in table 1.[711 ] although there is a difference in the rate of reported prevalence and whether the prevalence among diabetic patients is higher than that of normal population or not is still questionable , it can not be refused for the important of the problem on trigger digits among diabetic patients . summary on some important publications reporting the prevalence of trigger digits among diabetic patients however , there is no clear evidence that diabetes mellitus increases the risk for development of trigger digits . although it is not questionable that overall musculoskeletal problems increases in diabetic patients , there is no conclusion on the specific trigger digits problem . focusing on the existed evidences , trigger digits are common in old diabetic patients but not relating to sex , age , and type of diabetes.[71113 ] it is of interest that there is an observation that limited joint mobility is related to multiple digits involvement in diabetic patients with trigger digits , but there is no relationship with age , sex , type of diabetes . although the trigger digits can be seen and similarly diagnosed in both normal and diabetic patients , natural history of the condition in diabetic patients and the outcome of treatment may not be the same . it is reported that the insulin - dependant cases usually have more sever symptoms and multiple digits involvement and require surgical release for relief of symptoms . the steroid injection might be used although it does not provide a good success rate ( about 30%).[1719 ] in addition to use of steroid injection , the use of nonsteroidal anti - inflammatory drugs can provide a little relief from the symptoms.[1719 ] the use of steroid injection ( either methylprednisolone acetate or triamcinolone acetonide ) is proved to be safe ; however , there is also a report showing that the use of steroid injection can result in hyperglycemia . in addition , the recurrent rate is very high in the diabetes type 1 cases . focusing in detail , for the surgical treatment , it is used in the severe cases.[172426 ] the recommended surgical technique is surgical release of the first annular ( a1 ) pulley . the surgery might be a definitive treatment ( success rate up to 99% ) but the complications can be seen and the postsurgical physiotherapy is still required for a long time . of interest , a recent report indicated that diabetes was not a risk factor for trigger digits and postoperative complications of trigger digits surgery . however , closed observation and special care are still recommended for the cases with diabetes mellitus due to the risk for existence of microangiopathy . trigger digits is an important problem in diabetic patients , especially for the old ones . however , the cause result relationship between diabetes mellitus and trigger digits is still the topic for further study . in management , glucose control is important and the standard managements for the general population can be effectively used for the diabetic cases .

the problem of finger in the patient with diabetes mellitus is important consideration in diabetology . generally , peripheral neuropathy that manifests with finger paresthesia is common . however , some recent reports mention the concern on trigger digits in diabetic patients . in this brief article , the authors focus review and discussion on this specific topic . the searching of standard database , pubmed , on available publication on this area selecting by keywords trigger digits and diabetes mellitus was done and all derived papers were extracted and further synthesized in this review article . epidemiology and management of the condition are the mainly focused reviewed areas and presented in this article .

because of variations in pathological and clinical features of the disease , npd is classified into those with deficiency of acid sphingomyelinase activity ( types a and b ) , and those with defective intracellular processing and transporting of ldl cholesterol , which is known as type c. however , npd type c ( npc ) is different at the biochemical and molecular levels with a higher incidence than npa and npb . both types a and b are characterized by acid sphingomyelinase ( asm ) deficiency that leads to excessive sphingomyelin accumulation in all phagocytic cells and in neurons . normally , the enzyme activity of asm leads to the breakdown of sphingomyelin into ceramide and phosphorylcholine in lysosomes . generally , multiple organs such as spleen , liver , bone marrow , lymph nodes , lung and central nervous system are affected . clinically , npa is distinguished by failure of thrive , hepatosplenomegaly and progressive neurodegeneration . at molecular genetics level , the smpd1 gene is approximately 5 kb long and the coding sequence is divided among six exons . according to the human gene mutation database ( www.hmdb.cf.ac.uk ) , more than 100 different mutations ( including missense , nonsense , deletion , insertion , and splice site mutations ) have been reported in the smpd1 gene . to date for instance , motamedi et al reported a case of npb in iran and described the clinical course of his patient . furthermore , motamed et al reported a ten year study of liver biopsies in children 's medical center in tehran . most identified patients were affected with npd and glycogen storage disease type 1 ( gsd - i ) . in addition , majidzadeh et al reported a case of npd and compared clinical and molecular aspects of the disease . hoshmand et al presented a novel mutation in the smpd1 gene ( data not published ) . here , we present the first molecular genetics diagnosis of npa in an individual from southwest iran . a 2.5 year - old male , the first born child from first cousin parents was attending our center for genetic counseling and genetic diagnostics . the patient showed typical signs of the niemann pick disease , such as hepatosplenomegaly , developmental delay , mental retardation , and foam cells in the bone marrow , hypotonia , and cherry red maculae . unfortunately , measurement of the asm activity in the white blood cells failed and dna test was the only chance to establish a definite diagnosis . after obtaining informed consent , genomic dna was extracted from edta - anticoagulated whole blood by standard salting out procedures . selective amplification of all 6 exons was performed in a volume of 25 l reaction containing 10 pmol of each primer ( tag copenhagen a / s , fruebjergvej3 , denmark ) and 50ng of genomic dna . pcr was carried out by a set of designed primers using primer3out software ( http://frodo.wi.mit.edu/primer3/ ) . exon 2 was amplified by two separate primer pairs to assist subsequent sequencing reactions temperature profile of reactions were as follow : initial denaturation at 95c for 3 min , 35 cycles of 95c for 30s , 56 - 60c for 30s and 72c for 45s and a final extension at 72c for 7 min . direct sequencing of pcr products was carried out using abi automated sequencer 3700 according to the manufacture 's instruction ( abi 3700 , pe applied biosystems , foster city , ca , usa ) . sequence analysis was performed with the software bioedit ( version 7.0.5.3 ) . according to the human reference sequence nm_000543.4 , a homozygous single guanine deletion , c.740delg , was observed in exon 2 of the smpd1 gene , which results in a premature stop codon ( ctg > tga ) between codons 256 - 257 ( p.gly247alafs*9 ) ( fig . they are also obligate carrier . to confirm the pathogenic relevance of the detected deletion , 27 healthy individuals were tested . chromatogram of sequencing reactions from a ) affected individual , b ) heterozygote parents , c ) healthy person . the location of the novel deletion is indicated with black arrow and the position of the resulting stop codon is shown in black circle on the chromatogram . at bottom ( d ) , partial sequence of the smpd1 gene with corresponding codons is illustrated . to our knowledge by intensive literature searching , the present report demonstrates firstly the molecular genetics diagnosis of the npd in southwest iran . approximately 1 per 40,000 people of ashkenazi jewish descent has npa . in contrast , there is no information about frequency and distribution of different types of npd in iran , particularly in southwest iran . the disease refers to a group of disorders with deficiency in lipid storage , causing accumulation of fats in brain and liver that lead to serious damage or dysfunction of mentioned tissues . however , liver enlargement , brain damage , difficulty in walking , speaking and learning are characteristic symptoms for npa . diagnosis of this type of disease is usually made by measuring the asm activity in white blood cells . he was also referred to our molecular diagnostic center with the aim to find genetic cause of the disease . the smpd1 gene is the only gene considered to be associated with npa . here , we report an unreported deletion of single guanine in exon 2 of the smpd1 gene , causing a truncated gene product . exon 2 is unusually large , which encodes for 258 amino acids or approximately 44% of the entire asm polypeptide . however , the pathogenic nature of the novel deletion was confirmed by screening of healthy individuals . three common missense mutations account for more than 90% of the mutant alleles in individuals of ashkenazi jewish ancestry with npa . but in contrast to the ashkenazi jewish population , most affected individuals with npa showed in previous studies unique mutations in the smpd1 gene . consequently , identification of new npa cases increases the probability to discover new specific mutations for the given population . the present observations extend the mutation spectrum of the smpd1 gene in npa patients worldwide , and can be used for the prenatal or preimplatation genetic diagnosis , at least in southwest iran . therefore , prevention seems to be more effective strategy in the next pregnancy for this family and other families with positive history .

objectiveniemann pick disease ( npd ) type a ( npa : mim # 257200 ) is a lipid storage disorder with an autosomal recessive inheritance and occurrs by defect of the smpd1 gene encoding sphingomyelinase . disruption of this enzyme leads to the accumulation of sphingomyelin in brain and liver , which in turn causes dysfunction or damage of tissue.methodswe report firstly a 2.5 year old boy with npa in southwest iran . initially , the diagnosis was resulted on the basis of clinical symptoms . the genomic dna of the suspected individual was subjected to exon sequencing of the smpd1 gene . according to the human reference sequence nm_000543.4 , a novel single guanine deletion resulting in a frameshift mutation ( p.gly247alafs*9 ) was observed in the smpd1 gene that might be causative for the outcome of the disease.findingsthe present report is the first molecular genetics diagnosis of the npa in southwest iran . the detected deletion in the smpd1 gene is remarkable because of its novelty.conclusiondespite similar morbidity sga infants exhibited higher lethal complication rates following delayed meconium passage compared to aga infants .

clear - cell sarcoma ( ccs ) is a rare malignant connective tissue tumor that was first described by enzinger in 1965 . ccs occurs most commonly in adolescents and young adults and the patients aged > 60 years are rare . it has a high rate of local recurrence , regional lymph node metastasis , and distant metastasis [ 1 , 2 ] . ccs occurs most commonly in the deep soft tissues of the extremities , with rare involvement of the head , neck , and trunk . we experienced a very rare case of primary ccs in the mediastinum with successful surgical resection in an elderly patient . in october 2011 , a 63-year - old man presented with a mass in the right upper mediastinum on chest radiograph . computed tomography showed a large oval mass ( 55 55 85 mm ) with clear margins and heterogeneous enhancement in the right upper posterior mediastinum between the phrenic nerve and vertebrae ( fig . 1b ) , and 18f - fluorodeoxyglucose positron emission tomography showed abnormal uptake with a maximum standardized uptake value of 15.1 . the tumor was excised by video - assisted thoracoscopic surgery , with negative surgical margins . the tumor was soft , well circumscribed , encapsulated , and did not invade the pleura . histological examination of the resected tumor with hematoxylin and eosin ( he ) staining showed morphological features compatible with conventional soft tissue ccs . the tumor cells were distributed in nests separated by fibrous connective tissue , showing an alveolar pattern ( fig . the tumor cells had eosinophilic and clear cytoplasm and oval vesicular nuclei of varying sizes with characteristic prominent eosinophilic nucleoli . 2c ) , s-100 protein , calretinin , cd34 , cd56 , cd68 , and cd117 ; and negative for melan - a , cytokeratins ae1ae3 , cytokeratin cam5.2 , chromogranin a , desmin , caldesmon , myogenin , epithelial membrane antigens , cd57 , cd99 , and d2 - 40 . ccs is a very rare soft tissue neoplasm , which occurs in the extremities in 9095% of cases . our case was diagnosed with a primary ccs in the mediastinum . a search of the english literature revealed only one previously reported case of primary ccs in the mediastinum . recent cytogenetic studies showed that ccs is associated with the translocation t(12;22 ) ( q13;q12 ) ; this translocation is observed in up to 93% of patients with ccs , but never observed in malignant melanoma . in our case , we were unable to determine whether this translocation was present , because of the lack of availability of such analysis in japan . the rarity of ccs in the mediastinum makes it difficult to draw conclusions regarding prognostic factors . reported that complete excision of the primary tumor with wide surgical margins appears to be the optimal approach to treatment , with or without adjuvant radiation therapy . ccs is an aggressive malignant tumor , and unlike most soft tissue sarcomas , it often metastasizes to regional lymph nodes . in our case , we did not have a definitive diagnosis at the time of operation , and therefore we did not perform excision of the tumor with wide margins or dissect the regional lymph nodes . in most cases , ccs has a relentlessly progressive course and results in death because of widespread dissemination . the reported overall survival rates without local recurrence are 30% at 5 years and 16% at 10 years . some patients experience rapidly fatal progression , and late metastasis after many years of freedom from disease is also relatively common . we believe that regular long - term follow - up with computed tomography , magnetic resonance imaging , and 18f - fluorodeoxyglucose positron emission tomography examination is important to identify local recurrence or distant metastasis as early as possible .

we report a case of primary clear - cell sarcoma ( ccs ) in the mediastinum . in october 2011 , a 63-year - old man was admitted to our hospital for surgical resection . the tumor was completely excised by video - assisted thoracoscopic surgery . the tumor was well encapsulated and did not invade the pleura . histological examination led to a final diagnosis of primary ccs in the mediastinum . the patient remains alive without evidence of recurrence at 15 months after surgery .

a 78-year - old person , retired as school teacher with no history of any substance abuse or medical history . he had been suffering from bilateral knee pain diagnosed as osteoarthritis for the last 20 years and was not on any steroids . he presented with 1-month duration of altered behavior characterized by excessive psychomotor activity , emotional lability , increased self - confidence , excessive talkativeness , decreased need for sleep , and increased sense of energy level . there were a few occasions when he misrecognised his daughter as his wife who had passed away 6 months ago . on examination , he was an elderly obese person weighing 92 kg with bmi > 27 . mental status examination revealed increased irritability , increased psychomotor activity , and increased self - confidence and authoritativeness . he had similar behavior 3 years ago , diagnosed and treated as mania in the same hospital . there was positive family history in the form of his mother having had symptoms suggestive of postpartum psychosis . investigations including hiv , vdrl , serum vitamin b12 level , tft , eeg , routine hemogram , serum electrolytes , blood urea , and serum creatinine were normal . ecg revealed no abnormalities , except for a prolonged corrected qt interval ( qtc ) of 486 msec . his ct brain [ figure 1 ] showed cortical atrophy , especially pronounced in the temporal and frontal areas . the periventricular regions in the frontal lobe showed mild hypodensity suggestive of small vessel ischemic disease . he didnt fulfill international consensus criteria for behavioral variant of frontotemporal dementia ( ftd ) . ct brain shows frontal cortical atrophy ( top left ) , with frontal subcortical white matter hypodensities ( top right ) . widened sylvian fissures suggestive of temporal pole atrophy and basal ganglia calcifications are also seen ( bottom left ) . widening of temporal horns of lateral ventricles ( bottom right ) is further evidence of temporal lobe atrophy he was initiated with aripiprazole 5 mg / day because of his qtc being 486 msec . given his age , we chose aripiprazole as it is less sedating and has lower chances of producing postural hypotension . he also required intravenous lorazepam 2 mg sos for his agitated behavior for the first 2 days . aripiprazole was gradually increased to 15 mg , and by the end of 3 weeks he showed complete remission of his manic symptoms . at the time of admission in psychiatry ward , he scored 27 on mania severity on young 's mania rating scale ( ymrs ) and it came down to 4 at the end of 3 weeks . occurrence of first episode of mania in the elderly ( after 60 years age ) warrants a high index of suspicion for organic causes . , we did not find any obvious etiology for his mental illness , except for frontal and temporal atrophy and possible frontal sub - cortical white matter involvement . one possibility considered was that of ftd , but this was ruled out as he did not fulfill criteria for dementia and behavioral component of ftd . it is possible that the manic episodes were the initial manifestations of ftd in this patient and this will be tested only in the follow - up . there was family history of postpartum psychosis in his mother , which is associated with a family history of bipolar disorder and the index case had been diagnosed as mania 3 years ago with complete remission in the interval period . these two points and absence of any abnormalities in laboratory and clinical examination favored diagnosis of mania . aripiprazole has relatively high affinity for both 5-ht2a and d2 receptors similar to other atypical antipsychotics but differs from them due to its partial agonist activity at d2 and 5-ht1a receptors . it has a more favorable side - effect profile compared to typical and even atypical antipsychotics . aripiprazole has lesser propensity to cause extra - pyramidal symptoms , an important factor in the elderly . other desirable properties are lesser chance for causing side - effects like dyslipidemia , glucose intolerance , hyperprolactinemia , postural hypotension , sedation , qt prolongation , and weight gain . its efficacy has been proven as monotherapy in treating acute mania and in prophylaxis of bipolar disorder . hence , we chose aripiprazole for our patient in view of his already prolonged qtc interval and age of 78 years . this case is unusual in that age of onset of mania is very late ( 75 years ) and during the current second episode we could not find any organic etiology . hence , aripiprazole may be a safe and effective antipsychotic medication for the control of mania in the elderly .

new - onset bipolar disorder is rare in the elderly . symptom profile is similar to that in young adults but the elderly are more likely to have neurological co - morbidities . there are no case reports of elderly mania being treated with aripiprazole , an atypical antipsychotic . a 78-year - old gentleman presented to us with symptoms suggestive of mania of 1 month 's duration . he had similar history 3 years ago and a family history of postpartum psychosis in his mother . there were no neurological signs on examination and work - up for an organic etiology was negative except for age - related cerebral atrophy . he improved with aripiprazole and tolerated the medications well . the use of psychotropic medications in the elderly is associated with side - effects of sedation , increased cardiovascular risk , and greater risk of extra - pyramidal side - effects . the use of partial dopaminergic antagonists like aripiprazole may be useful in the balancing of effects and side - effects .

the difficulty in making the correct diagnosis because of the multitude of coinfections and comorbidities in the hiv population led the authors to a first erroneous diagnosis almost compromising the results of treatment . this experience is discussed further in the text . the patient wpo , from the city of so paulo ( brazil ) , a 75-year - old caucasian male , had been receiving antiretroviral treatment in hospital das clnicas of so paulo , since being diagnosed with hiv 12 years earlier ( now taking lamivudine , tenofovir , atazanavir , and ritonavir for the last three years ) . he was in a good general condition , with good viral and immunological control ( undetectable viral load and cd4 count of 653/ml ) . other laboratory tests were normal , and he did not have any other coinfections , had no drug addiction , and no other comorbidities . he sought medical assistance because of a complaint of patellofemoral pain in his right knee that had started one year earlier with increasing local volume and progressive inability to perform active extension . he had a knee extension lag of 30. he was able to walk only with a stick . the increased volume was concentrated below the patella and posterior to the patellar tendon , without local inflammatory signs , history of trauma , and infection . in addition , a tendinopathy with partial chronic lesion of the patellar tendon probably explained the clinical findings . it was decided first to perform a magnetic resonance imaging ( mri ) [ figures 1 and 2 ] . this revealed the presence of edema and thickening of the infrapatellar fat , with the formation of a nodule measuring 2.01.62.0 cm , with low signal and no impregnation with contrast . the patellar tendon was found thickened , with foci of partial ruptures and with peritendinous edema . sagital mri image , showing thickening of hoffa 's fat pad and adjacent synovial membrane , with foci of partial rupture of the patellar tendon axial mri image , showing a solid fibrous mass in hoffa 's fat pad the treatment for this situation is essentially nonsurgical . since our patient did not show any improvement through physiotherapy and drug treatment , surgical treatment was indicated . this was done with the aim of exploring the patellar tendon and reconstructing it if necessary , along with partial resection of hoffa 's fat and the nodule , with pathological analysis of the tissue . the intraoperative appearance of the knee showed an intact patellar tendon with an infiltrated tissue around hoffa 's fat , without any local inflammatory reaction [ figure 3 ] . it was decided only to biopsy this tissue and culture for bacteria , mycobacteria , and fungi . intraoperative aspect of the lesion in hoffa 's fat pad , with an intact patellar tendon none of the cultures was positive . on the 14 day after the operation , the results from the anatomopathological examination revealed that the nodule consisted of a high - grade malignant fibrohistiocytoma , without sufficient margins of resection . after ruling out metastasis [ by thoracic and abdomen computed tomography ( ct ) and bone scintigraphy ] , our patient underwent bloc resection of the entire joint , including the distal femur , proximal tibia , patella , and musculature of the distal quadriceps . the knee joint was reconstructed using an endoprosthesis , which was covered by rotating a flap from the medial gastrocnemius muscle and the extensor mechanism was reconstructed using the sartorius muscle . the patient has a good functional outcome , walking with the aid of one crutch and without any recidive after 18 months of the surgery . the most common causes for this pain are degenerative or traumatic modifications of the patellar and trochlear cartilage , tendonitis , inflammatory processes of hoffa 's fat , and patellar dysfunction caused by muscle weakness , shortening , or instability . the pain - specific localization was suggestive of an inflammatory process in hoffa 's fat or chronic partial lesion of the patellar tendon , which would explain the active extension deficit . within the context of considerable increase in life expectancy among patients infected with hiv achieved since the introduction of highly active antiretroviral therapy ( haart ) , certain osteoarticular consequences of prolonged duration of viral infection and its treatment have been observed , such as osteopenia / osteoporosis , osteonecrosis , carpal tunnel syndrome , adhesive capsulitis of the shoulders , modifications of body shape , and changes in lipid and glucose metabolism . a care and study group called the bone - hiv group was created in our hospital to assist patients with hiv / aids presenting any orthopedic complaint . the medical literature on this orthopedic abnormality is very sparse , and we have not found any reports or epidemiological characterization of patellofemoral pathological conditions among this group of patients . one of the few studies on this subject in the literature described abnormalities in hoffa 's fat in patients with hiv , which may have an etiological link to patellofemoral pain . so , the typical changes induced by long - term infection and therapy of hiv may have a negative impact on the extensor mechanism of the knee , which led us to an erroneous initial diagnosis , instead of a much more aggressive disease . malignant fibrohistiocytoma was first described in 1964 and is currently known as high - grade pleomorphic sarcoma in adult life . malignant fibrohistiocytoma usually presents as a deep painless mass , without other local or systemic symptoms . the staging depends on the histological grade , size , and presence of metastasis , which is the most important prognostic factor regarding survival . radiotherapy is administered in most cases , with good results relating to local control , either before or after the surgery . the role of chemotherapy is unclear , but it can be administered particularly in cases with a high risk of metastases . in this case , chemotherapy was not used because of unclear evidence of benefit and the risk of side effects . as the case evolved , it became clear that the abnormalities in the patient 's knee were unrelated to his chronic hiv infection . however , this case once again raises the issue of lack of knowledge of the long - term changes caused by this disease . since there have been sporadic reports of abnormalities of hoffa 's fat among such patients , along with the nonspecific presentation of the condition in our patient , we were led to believe that his condition could have been related to hiv . we again emphasize that studies on osteoarticular changes ( such as bone density , muscular mass , joint mechanics , and cartilage loading ) induced by chronic hiv infection need to be conducted , to epidemiologically define this population better and diminish the frequency of erroneous diagnoses among patients with hiv / aids .

this case report describes a patient presenting with anterior knee pain ( extensor mechanism pain ) , a poorly studied complaint in the hiv population . the final diagnosis was malignant fibrohistiocytoma , a rare condition among knee pathologies , successfully treated with endoprosthesis after tumor resection . this article focuses on what the authors learned after treating this patient , particularly on the difficulty in making a correct diagnosis of this group of patients due to lack of adequate epidemiological characterization . by assuming that the pathology was related to long - term infection and treatment of hiv ( knee hoffitis ) , the authors underestimated the gravity of the case , almost compromising the result of treatment .

( baill . ) is a source plant of traditional chinese medicine . the s. chinensis fruit ( sf ) , which has five - flavored fruits ( salty , pungent , bitter , sweet and sour ) , is called wuweizi in china . it naturally distribute in china , russian , korea and japan and was used in treatment of diseases including liver injury , tumor inhibition , urinary tract disorders , insomnia and palpitation , even inhibit both hiv-1 rt - associated dna polymerase activity and virus replication . in addition to its application as a chinese herbal medicine . it is also used for making beverages , tea , wine , health food industries and cosmetics . therefore , recent research has been focused on extracting active ingredients and identifying function . despite of the importance of s. chinensis , the next generation sequencing technology has dramatically improved the efficiency and speed of gene discovery . two cultivars yanhong ( red skin ) and jinwuwei ( white skin ) were grown in orchard located in zuojia town , jilin city , jilin province , china ( 440647 n 1260718 e ) that belong to the plant resources nursery of institute of special wild economic animal and plant science , chinese academy of agricultural sciences . fours samples , including fruits and skins , were harvested and immediately frozen in liquid nitrogen for further experiments . total rna was extracted using modified ctab method , library construction and high - throughput sequencing for each sample was performed at a contract sequencing company ( novogene , china ) . the cdna library was sequenced using an illumina hiseq2500 platform . with the purpose of determining the red fruit , white fruit , red skin of red fruit and white skin of white fruit of s. chinensis . we obtained a total of 72.5 million , 55.1 million , 68 million and 69.3 million raw data reads from four sequencing libraries prepared , respectively ( table 1 ) , > 94.9% bases has a q value 20 ( an error probability of 0.035% ) . after cleaning and quality checks , the de novo assembly of all sequencing data using the trinity method . it generated 92,415 all - transcripts with an average length of 496 bp and an n50 of 1466 bp ; and 71,443 all - unigenes were achieved . of these , 46,461 ( 65.0% ) were 200500 bp , 11,322 were 5001000 bp , 8612 were 12 kb and the remaining 5078 were > 2 kb ( table 2 ) . the results provides us useful information for further explorer the gene synthesis pathways of active ingredients . two cultivars yanhong ( red skin ) and jinwuwei ( white skin ) were grown in orchard located in zuojia town , jilin city , jilin province , china ( 440647 n 1260718 e ) that belong to the plant resources nursery of institute of special wild economic animal and plant science , chinese academy of agricultural sciences . fours samples , including fruits and skins , were harvested and immediately frozen in liquid nitrogen for further experiments . total rna was extracted using modified ctab method , library construction and high - throughput sequencing for each sample was performed at a contract sequencing company ( novogene , china ) . with the purpose of determining the red fruit , white fruit , red skin of red fruit and white skin of white fruit of s. chinensis . we obtained a total of 72.5 million , 55.1 million , 68 million and 69.3 million raw data reads from four sequencing libraries prepared , respectively ( table 1 ) , > 94.9% bases has a q value 20 ( an error probability of 0.035% ) . after cleaning and quality checks , the de novo assembly of all sequencing data using the trinity method . it generated 92,415 all - transcripts with an average length of 496 bp and an n50 of 1466 bp ; and 71,443 all - unigenes were achieved . of these , 46,461 ( 65.0% ) were 200500 bp , 11,322 were 5001000 bp , 8612 were 12 kb and the remaining 5078 were > 2 kb ( table 2 ) . the results provides us useful information for further explorer the gene synthesis pathways of active ingredients .

the fruit of schisandra chinensis turcz . ( baill . ) , namely wuweizi in china , is a well - known herbal medicine and health food . at present , research focused on the extraction of effective chemical component and function identification . little known about the secondary metabolism gene pathway of chemical composition . its fruit color usually red , however , the white fruit color variation has been found . it made us interested in exploring which gene change lead to this result . in order to understand the genetic background of s. chinensis , we performed a transcriptome analysis of s. chinensis , including red fruit and skin of yanhong cultivar and white fruit and skin of jinwuwei. we obtained 26.4 gb raw data ( ncbi accession number : ssr4449123 ) . de novo transcriptome assembly using trinity revealed 92,415 transcripts and generated 71,443 unigenes . all unigenes were annotated in database.this study provides transcriptome of s. chinensis , which might be useful for comparative transcriptome analyses and understand gene expression of secondary metabolites .

neuroendocrine ( ne ) carcinoma of the breast was first described by cubilla and woodruff in 1977 . primary ne carcinomas of the breast are rare and represent about 2 - 3% of breast carcinomas . they are much rarer in the male breast occurring in less than 1% of the cases . ne breast cancers encompass a heterogeneous group of tumors exhibiting morphological features similar to those of ne neoplasms of the gut and lung . they invariably express one or more ne markers ( neuron specific enolase , chromogranin , synaptophysin ) in at least 50% of the tumor cells . we report one such rare case in male breast diagnosed by fine needle aspiration cytology ( fnac ) . an 80-year - old male presented with a mass in the right breast of 10 years duration with rapid progression in growth since the previous 3 months . mammography showed a well - defined mass in the right breast with ipsilateral axillary lymphadenopathy . fine - needle aspiration cytology showed cellular smears with dispersed single cells and loose sheets . many nuclei showed moderate anisocytosis , irregular nuclear contours , prominent nucleoli and sprinkled chromatin [ figure 1a and 1b ] . considering these features , a cytological diagnosis of ne carcinoma of the breast ( a ) highly cellular smear , dispersed cells and loose sheets ( pap , 100 ) . ( b ) tumor cells with anisocytosis , irregular nuclear borders , prominent nucleoli and sprinkled chromatin ( pap , 400 ) the patient underwent right radical mastectomy with axillary lymph node dissection . gross examination revealed a tumor measuring 10 cm 8 cm 8 cm , with a solid , grey - white appearance and a focal cystic area [ figure 2a ] . histopathological sections studied showed a malignant tumor with cells in solid nests , trabecular and organoid patterns , separated by delicate fibro - vascular connective tissue stroma . a focal area in the tumor also showed features of invasive papillary carcinoma [ figure 2c ] . four out of the six resected lymph nodes showed metastatic deposits from the primary breast tumor . ( a ) gross specimen showing solid , grey - white tumor with a cystic area . ( c ) focal area in the tumor with features of papillary carcinoma ( h and e , 400 ) . ( d ) tumor cells with cytoplasmic chromogranin positivity ( ihc , 400 ) immunohistochemical staining revealed cytoplasmic positivity for chromogranin which confirmed the ne nature of the tumor [ figure 2d ] . to exclude a non - mammary primary site , the chest , abdomen and pelvis were thoroughly examined for abnormalities , but none was detected . final diagnosis of primary pure solid ne carcinoma of the breast with a minor component of papillary carcinoma and metastasis to ipsilateral axillary lymph node was arrived at , following which the patient received adjuvant chemotherapy . features of primary pure neuroendocrine breast carcinomas ( nebc ) were considered to be special features within conventional breast carcinomas until recently . in 2003 , the world health organization classification of breast tumors definitely established that , the immunohistochemical expression of ne markers in more than 50% of the tumor cell population is the unique requisite for nebc diagnosis . but , invasive papillary carcinoma associated with ne carcinoma in the male breast as seen in the present case is an unusual occurrence . endocrine hormone related syndromes are rare in primary nebc despite the presence of widespread disease . the tumor cells in ne carcinomas of the breast are argyrophilic in contrast to the gut and lung carcinomas which may be of either argyrophil or argentaffin types and are hence called argyrophilic carcinomas . argyrophilic carcinomas of the male breast are ne tumors containing predominantly chromogranin b. most argyrophilic tumors show uniform cellularity and expansive growth as in the present case . despite being a distinct morphological and immunohistochemical entity , no statistically significant differences are seen between argyrophilic and the other commoner types of male breast carcinomas . stage on an average is higher than for the other breast carcinomas , as in the present case , since more than 50% of the patients show lymph node metastasis at the time of presentation . however , in the present case , the predominant component was ne carcinoma which was associated with a minor component of papillary carcinoma . about 50% of well - differentiated and moderately differentiated ne carcinomas express chromogranin a and b. only 16% express synaptophysin . mucin as seen in the present case , as also observed by stita et al . , in 26% of cases and was considered to be a favorable prognostic factor by them . ne breast carcinomas are observed not to exhibit aggressive behavior despite the presence of adverse prognostic factors . good prognosis in these tumors relates to their intrinsic nature and high rate of treatment responses . ne carcinoma in male breast is a rare entity but does occur and can be diagnosed on fnac . however , it is important to distinguish the primary nebc from metastatic carcinoma because the management and prognosis differ . primary ne carcinoma of the breast may pose a cyto - histologic diagnostic challenge due to the rarity of its occurrence and paucity of literature . nevertheless , it is an entity which no pathologist can afford to miss since it is less aggressive and shows a high rate of treatment response .

primary neuroendocrine ( ne ) carcinoma of the male breast is very rare . ne breast cancers encompass a heterogeneous group of tumors exhibiting morphological features similar to those of ne tumors of the gut and lung . they express one or more ne markers in at least 50% of the tumor cells . they are rare lesions representing about 2 - 3% of all breast cancers and more frequently affecting elderly patients . the present case report deals with a ne breast carcinoma in an 80-year - old male who presented with a right breast mass and axillary lymphadenopathy . the cytological features were suggestive of ne carcinoma . a thorough clinical evaluation helped confirm the primary nature of the tumor . the histopathology and immunohistochemistry helped confirm the cytological diagnosis . the histogenesis and prognostic implications of this rare breast tumor with predominant ne differentiation , unusually occurring in a male , is discussed here .

extranodal nhl can occur in any visceral or non - visceral organ , but there are several predominant sites , including the stomach , small intestine , skin , and brain . nhl in the breast or testis is relatively rare , representing 0.38%-0.7% and 1%-2% of all nhl , respectively . these types of lymphoma are generally high - grade lymphomas with an aggressive clinical course . the main treatment strategy for diffuse large b - cell lymphoma ( dlbcl ) with involvement of the breast is an anthracycline - containing chemotherapy with or without radiotherapy . the role of central nervous system ( cns ) prophylaxis remains controversial despite the risk of cns relapse , due to unproven benefit . on the other hand , anthracycline - based chemotherapy combined with locoregional radiotherapy to the contralateral testis and cns prophylaxis the 5-year overall survival rate from previous reports varies from 26% to 71% in breast lymphoma and 56%-87% in testicular lymphoma . here we report a patient with dlbcl involving both the breast and testis who was successfully treated with complete resection of the involved testis ; immunochemotherapy with rituximab , cyclophosphamide , doxorubicin , vincristine , and prednisolone ( r - chop ) ; and prophylactic radiotherapy to the contralateral testis . a 76-year - old man visited our hospital ( asan medical center , seoul , korea ) with a mass on his right breast first being recognized two months ago . he had no b symptoms and an unremarkable medical history , except for hypertension . on physical examination he had a rubbery , non - tender , mobile mass of approximately 4 cm on his right breast . there were no other palpable lymph nodes in the axillary , neck , or inguinal area , but his right testis was slightly harder than the left testis , without a definite mass . iu / l , and 2 microglobulin was 1.8 g / ml . screening tests for human immunodeficiency virus , hepatitis c virus , and hepatitis b virus were all negative . on mammography , a heterogeneous , dense , lobulated mass - like lesion was observed in the subareolar portion of the right breast . the pathologic specimen from core needle biopsy revealed diffuse proliferation of large , atypical lymphoid cells ( fig . 1b ) , bcl-6 , and irf4/mum1 , but was negative for cd10 . in situ hybridization for epstein - barr virus was also negative . based on these pathologic findings , the patient was diagnosed with dlbcl . a staging work - up including bone marrow biopsy with aspirate , positron emission tomography computed tomography ( pet - ct ) , and abdomen and chest computed tomography ( ct ) revealed no evidence of other nodal or marrow involvement . however , the pet - ct showed increased metabolism in the right testis , with a maximum standardized uptake value of 8.4 ( fig . pathologic examination revealed a well - defined ovoid mass ( 3.82.51.6 cm ) , which was confirmed as dlbcl ( fig . , he was finally diagnosed with dlbcl involving both the breast and testis , with an ann arbor clinical stage of 4ea . the patient received a total of six cycles of immunochemotherapy ( 375 mg / m rituximab on day 1 , 750 mg / m cyclophosphamide on day 1 , 50 mg / m doxorubicin on day 1 , 1.4 mg / m vincristine on day 1 , and 50 mg prednisolone bid on days 1 - 5 [ r - chop ] ) . follow - up ct and pet - ct after four cycles and six cycles of r - chop immunochemotherapy confirmed a complete response . after six cycles of r - chop immunochemotherapy , prophylactic radiotherapy of 25 gy with 10 fractions was administered to his left testis . he has been followed at the outpatient clinic regularly without evidence of relapse for 17 months . extranodal nhl of the breast is uncommon , and its occurrence in male patients is extremely rare . table 1 provides an overview of previously reported cases of male primary breast lymphoma ( pbl ) [ 3 - 13 ] . none of these cases presented with metastatic disease at first presentation , but three patients relapsed at other sites , including the cns , bone marrow , cervical lymph nodes , and adrenal glands . the prognosis of pbl is somewhat variable , with the 5-year survival rate ranging from 26%-71% . according to some reports , progression to cns is relatively more common in pbl than in other nhl , ranging from 12%-27% . recent studies , however , suggest that routine cns prophylaxis should not be given despite the high risk of cns relapse in pbl , because there is no survival benefit . in primary testicular lymphoma ( ptl ) , previous studies report a continuous pattern of relapse , even at 10 - 14 years after initial therapy . similar to pbl , common sites of relapse include extranodal sites such as the cns and contralateral testis . the risk of cns relapse is reported to be 20% and 35% at 5 and 10 years , respectively . although bilateral involvement is uncommon at diagnosis , up to 35% of ptl patients develop contralateral testicular involvement later in their clinical course , which provides a rationale for prophylactic radiotherapy to the contralateral testis . anthracycline - containing chemotherapy ( i.e. , chop ) is considered the standard treatment option for early - stage dlbcl . a number of cases benefitted from radiotherapy upon relapse on the contralateral side , which improved overall and progression - free survival in ptl . the role of additional radiotherapy to the involved side of breast , however , is yet to be determined , although it did show positive effects on progression - free survival and the risk of ipsilateral locoregional progression . here , we present the first reported case of dlbcl with simultaneous breast and testicular involvement , without any nodal presentation . the patient received immunochemotherapy ( r - chop ) and prophylactic radiotherapy to the contralateral testis because of the high relapse rate of testicular lymphoma . in summary , dlbcl involving both the breast and testis was successfully treated with multimodal strategies and showed a favorable response without evidence of recurrence .

here we report a case of a 76-year - old man with diffuse large b - cell lymphoma ( dlbcl ) with simultaneous involvement of the right breast and left testicle . the patient underwent complete resection of the involved testis , followed by immunochemotherapy with rituximab , cyclophosphamide , doxorubicin , vincristine , and prednisolone ( r - chop ) and prophylactic radiotherapy to the contralateral testis . following this multimodal therapy , he achieved a complete response . this is a rare case of dlbcl involving both the breast and the testis in a male patient .

first - line procedural investigations for non - specific epigastric pain include endoscopy and endosonography , combined with biopsy of suspicious areas in the upper gastrointestinal tract . despite high sensitivity and specifity , obtaining a definite histopathologic differentiation is sometimes unsuccessful , particularly if biopsy is not representative , e.g. because of tumor bleeding into the affected tissue . in such a case , the single remaining diagnostic option is a curative laparoscopic endoscopically - assisted wedge - resection of the stomach . we present an interdisciplinary case report in which a tumor of the stomach , suspicious for gist , was removed surgically and was found to be a benign glomus tumor by definitive histology . a 44-year old patient presented with relapsing epigastric pain of variable intensity and tarry stool , beginning three days earlier . there were no clinical or laboratory findings to suggest an acute posthemorrhagic anemia ( hemoglobin 14.7 g / dl , hematocrit 43.2% , pt 118% , aptt 27 s ) . upper endoscopy and endosonography were performed , revealing a spherical , submucosal , solid tumor approximately 50 mm in diameter located in the pyloric antrum ( fig . overlying ulceration was considered the likely source of bleeding , and fine needle biopsy of the lesion ( 19 g ) was performed , followed by preventive clip - application . an endosonographic picture with a poorly reflective , non - homogeneous pattern and echo - free areas was compatible with a 35 30 mm gist ( fig . investigations thus far were inadequate to exclude a malignant process , and surgery ( endoscopically - assisted laparoscopic wedge - resection of the stomach ) was indicated . histological section of the surgical specimen revealed a rare benign glomus tumor ( positive reaction on markers specific for glomus tumor ( vimentin / actin ) , fig . glomus tumor is a ( quite ) rare neoplasm and despite local invasion of vessels is mostly benign . it is often found in the skin ( particularly in the dermis / subcutaneous tissues of the limbs ) , but can also be found in the gastrointestinal tract ( usually intramurally in the mucosa / submucosa and serosa ) as well as other solid organs . the present assumption that the first glomus tumor of the stomach was identified in 1948 and described with another two cases in 1951 smol'iannikov wrote that the first glomus tumor of the stomach was clearly described in a 64-year old man in 1928 by talijeva . furthermore , the first malignant glomus tumor of the stomach was diagnosed in 1939 by kirschbaum et al . in a 40-year old man . there are case reports of malignant glomus tumors of the stomach in girls aged 1214 years , published by yannopoulos et al . . in addition , there have been a number of reports pertaining to glomus tumors of solid abdominal / retroperitoneal organs and of the colon [ 6 , 7 , 8 ] . there is no gender bias in the incidence of glomus tumors but their peak incidence occurs between the fourth and sixth decade of life . immunohistochemically , most glomus tumors show a positive expression of vimentin / actin without expressing chromogranin a , neuronspecific enolase ( nse ) , carcinoembryonic antigen ( cea ) or epithelial membrane antigen ( ema ) . the rarity of glomus tumor , its variable organ involvement , its non - specific symptoms at presentation and the often equivocal results of standard first line investigations all contribute to diagnostic difficulty . endoscopic and endosonographic images in glomus tumors of the stomach show a solid , submucosal tumor with or without ulceration and do not differentiate it from other important diagnoses , e.g. gist , neuro - endocrine neoplasia ( carcinoid ) , angiomyoma or lymphoma . hence , presurgical diagnostic confirmation is often impossible . only immunohistochemical analysis of representative biopsies ( gist : positive reaction with cd-117 antibodies and missing expression of glomus tumor typical actin / vimentin ) can confirm the diagnosis , and hence aid the clinician in determining appropriate therapy and prognosis [ 9 , 10 , 11 ] . compounding pre - surgical diagnostic difficulties , there have also been reports of malignant transformation of glomus tumor . therefore , surgery or en bloc endoscopic enucleation is in most cases the remaining diagnostic and therapeutic option [ 12 , 13 ] . a definite immunohistochemical confirmation of the diagnosis is essential , because the prognosis of a potentially malignant lesion is otherwise unpredictable . in the case presented , a patient with recurring epigastric pain and melaena , there was an endoscopic and endosonographic finding of a submucosal tumor of the gastric antrum . given the non - diagnostic biopsy result and the ongoing risk of gastrointestinal bleeding , endoscopically assisted laparoscopic wedge - resection of the stomach was performed as a combined diagnostic and therapeutic procedure . histological and immunohistochemical analysis of the resected tissue showed an entirely removed ( ro ) glomus tumor . unlike gist , if complete removal of a benign glomus tumor ( ro ) is verified histologically , there is no indication for further specific therapy [ 14 , 15 ] . sonographic ( for solid organs ) and endoscopic follow - up for early detection of recurrence or metastasis constitutes the most reasonable postoperative follow - up .

glomus tumor is an infrequent and in most cases benign mesenchymal neoplasia which affects subcutaneous / submucosal tissue and occurs in the gastrointestinal tract , solid organs ( e.g. liver , kidney ) and the extremities . visceral glomus tumor of the stomach generally presents with non - specific epigastric pain , loss of appetite and gi bleeding ( melaena ) , often without haemodynamic instability . macroscopic appearances on upper gi endoscopy are non - diagnostic . endosonographic appearances are generally heterogenous and poorly - reflective , hence fail to differentiate glomus tumor from other potential diagnoses . histological confirmation of the diagnosis is only possible when a fine needle biopsy is inclusive of abnormal tissue . these difficulties in diagnosis mean that in many cases , only immunohistochemical analysis of surgically resected tissue can distinguish glomus tumor from several possible differentials . therefore , endoscopically - assisted laparoscopic curative wedge - resection of a lesion suspicious for glomus tumor of the upper gastrointestinal tract must be considered first - line in terms of a combined investigative and curative approach .

a 37-year - old man of english descent presented with long - standing photophobia , reduced vision , and retinal pigmentary changes . he subsequently developed lymphoma in the left kidney , treated by nephrectomy and rituximab , and two bowel lymphomas treated with chemotherapy and rituximab . at age 29 , he developed peripheral myopathy when dd was diagnosed on muscle biopsy . he took cyclosporin 100 mg bd , mycophenolate 500 mg bd , ramipril 10 mg daily , amlodipine 10 mg daily , pravastatin 20 mg daily , ezetimibe 10 mg daily , prednisolone 5 mg daily , and aspirin 100 mg daily . on examination , he was highly myopic ; best - corrected snellen visual acuity ( va ) was 20/30 in the right eye and 20/200 in the left eye . fundoscopy revealed midperipheral pigmentary changes , with near - complete loss of rpe in the remaining retina . cirrus spectral - domain optical coherence tomography ( sd - oct ) ( zeiss , germany ) scanning demonstrated asymmetric macular cysts in the inner retinal layers and patchy photoreceptor loss in both maculae [ fig . 1 , table 1 ] . full - field erg testing was performed using a gold foil electrode according to the international society for clinical electrophysiology of vision standards ( lkc technologies , inc . ) . this showed non - specific abnormalities : scotopic responses were of reduced amplitude and normal implicit time ; photopic responses were of normal amplitude but increased implicit time . fundus photographs right eye ( a ) , left eye ( b ) , infrared images right eye ( c ) , left eye ( d ) , and horizontal spectral - domain macular oct scans at baseline right eye ( e ) , left eye ( f ) , and after treatment right eye ( g ) , left eye ( h ) with oral acetazolamide of a patient with histologically confirmed danon disease . these demonstrate the peppered pigmentary mottling and cystic - appearing lesions within the macula with photoreceptor loss and minimal response to treatment retinal thickness and visual function in response to treatment treatment with the carbonic anhydrase inhibitor ( cai ) dorzolamide 2% topically bd to both eyes was initiated . following 30 weeks of treatment , the patient reported no change in central vision or glare symptoms . there was no significant change in vision , central subfield thickness , or macular cube volume . he was then treated with acetazolamide 500 mg daily while cyclosporine levels and renal function were monitored . following 18 weeks of treatment , he reported no change in central vision or glare symptoms . best - corrected va was 20/40 in the right eye and cf in the left eye . central subfield thickness , macular cube volume , and repeat erg testing ( roland , germany ) showed no significant changes . danon retinopathy is a rare x - linked disorder related to mutations in the lamp2 gene . the patient showed characteristic signs of danon retinopathy and his erg results were typical of the disease . the patient was myopic , but the macular changes are not typical of pathologic myopic foveoschisis , typically a thickened retina at the posterior pole , with hyporeflective splitting between the outer and inner retina , or of progressive myopic maculopathy , both of which are usually detected in patients with a posterior staphyloma . patients with retinal dystrophies have been reported to have both cystoid macular edema ( cme ) and non - cme macular cysts . the patient refused fluorescein angiography , which is the diagnostic test to differentiate between cme and non - cme cysts , but the asymmetry of cystic changes seen on oct is typical of cme associated with late hyperfluorescence on intravenous fluoresce in angiography and strongly suggests that the cysts are cme rather than non - cme cysts . the cme is probably due to leakage of fluid through the rpe consequent to failure of the rpe pump . the reason for abnormal lamp2 protein resulting in presumed rpe pump failure is not known . to our knowledge , this is the first reported case of cme in histologically confirmed dd . in our case , topical dorzolamide 2% eye drops and oral acetazomide were not effective in the treatment of cme associated with dd . the reasons for lack of effect may have included low dose of acetazolamide , limited by renal disease ; pre - existing photoreceptor atrophy and long - standing visual loss , particularly in the left eye ; and pre - existing rpe atrophy , given the mechanism of action of cai via rpe acidification which helps to enhance chloride transport , and consequently water transport . also , any non - cme macular cysts may not respond to cais . lack of effect of cai is in contrast to previous studies which have demonstrated a beneficial effect of cais in patients with retinal dystrophy and cme such as retinitis pigmentosa , and patients with macular cysts , including x - linked retinoschisis and enhanced s - cone syndrome , although some patients fail this treatment . despite lack of response in our patient , we recommend consideration be given to carbonic anhydrase inhibition for patients with cme associated with danon retinopathy , given the response seen in other retinal conditions with associated cme and macular cysts with this treatment . a further treatment option to consider for similar patients is intravitreal bevacizumab , which this patient refused . in conclusion , to our knowledge our patient is the first reported case of danon retinopathy with cme .

to report a patient with danon retinopathy with cystoid macular edema treated with topical dorzolamide 2% eye drops and oral acetazolamide . a 37-year - old caucasian man with danon disease treated with topical and oral carbonic anhydrase inhibitors participated in the study . examinations performed before and during treatment included visual acuity ( va ) , spectral - domain optical coherence tomography , and electroretinography . following total 48 weeks of treatment , va decreased from 20/30 od , 20/200 os , to 20/40 od , cf os . the mean central retinal thickness was unchanged from baseline 263 m od , 226 m os , after treatment 283 m od and 202 m os . in our case , carbonic anydrase inhibitors were not effective . however , a general recommendation can not be given based on a single case .

individuals with a hematologic malignancy may have an immunosuppressive condition and develop cutaneous or invasive bacterial infections . the infections may be a first sign of a malignancy or a sign of a relapse . acute promyelocytic leukemia ( apl ; acute myeloid leukemia m3 ) is caused by balanced reciprocal chromosomal translocation t(15;17 ) , which produces an oncogenic protein pml - rara by fusion of the promyelocytic leukemia gene ( pml ) and the retinoic acid receptor a gene ( rara ) . apl is created by a blockage of differentiation , resulting in overproduction of immature myeloid cells of promyelocytes in the bone marrow . we herein report a 71-year - old man with cellulitis as a first sign of apl . a 71-year - old man was referred to us on october 2011 with a painful eruption on the right thigh that had appeared 12 days earlier . a physical examination revealed a swollen and painful erythematous lesion with an elevated temperature ( 38.6c ) on the right thigh ( fig . laboratory blood examination results were as follows : white blood cell count 1,300/l with neutrophils 18.4% ( band neutrophils 10.0% and segmented neutrophils 8.4% ) , lymphocytes 56.0% , monocytes 0.3% , eosinophils 0% , basophils 0% , metamyelocytes 1.3% and leukemic cells 24.0% ; red blood cells 3.29 10/l ; hemoglobin 11.5 g / dl ; platelets 11.9 10/l ; c - reactive protein 18.526 mg / dl ; soluble interleukin-2 1,249 u / ml ; ferritin 607 ng / ml ; c3 170 mg / dl ; c4 36 mg / dl ; ch50 73.8 u / ml ; fibrinogen 632 mg / dl ; fibrin degradation product 24.1 g / ml ; antithrombin iii 109% ; thrombin - antithrombin iii complex 6.3 ng / ml ; plasmin - a2 plasmin inhibitor complex 3.1 g / ml ; d - dimer 15.8/g / ml , and endotoxin less than 5.0 pg / ml . blood cultures showed no bacterial growth . g - band testing of twenty bone marrow cells showed 46,xy , t(15;17)(q22;q12 ) in 19 cells and 46,xy in 1 cell . all - trans retinoic acid ( atra ) , idarubicin hydrochloride , and cytarabine were administered after the bacterial infection had been eliminated . one month after the administration of atra , a sample of bone marrow cells contained the following : myeloblasts 2.1% ; promyelocytes 3.5% ; myelocytes 21.8% ; metamyelocytes 20.2% ; band neutrophils 12.0% , and segmented neutrophils 5.6% . apl cells can be forced to differentiate in the presence of atra . in this case , a bone marrow examination indicated that the apl cells differentiated into maturing cells after the administration of atra . patients with leukemia are predisposed to pancytopenia , and may show infectious disorders resulting from leukocytopenia , purpura resulting from thrombocytopenia , and shortness of breath resulting from erythrocytopenia . cellulitis may develop secondary to a bacterial infection in patients with leukemia , including apl . cellulitis is an inflammation of loose connective tissue of dermal and subcutaneous tissue , and is caused by bacterial infection . however , cellulitis without leukocytosis may be present in patients with malignant hematologic disorders as shown here , or in persons with cold cellulitis by cutaneous leishmaniasis or leprosy . girmenia et al . reported that their analysis of septicemias in apl patients receiving atra and idarubicin showed a significantly lower rate of bloodstream infections , even though patients receiving atra occasionally suffered life - threatening and lethal infections . the authors noted that 6 of 89 patients with apl withdrew from antileukemic treatment due to infections . infection control before and during the treatment is indispensable for individuals with apl , even though septicemias are less frequent in apl than in other leukemias . dermatologists and hematologists should keep in mind that patients with a hematologic malignancy , such as apl , can develop cellulitis with leukocytopenia .

patients with hematologic malignancies are immunosuppressive and may develop cutaneous or invasive infections as a primary sign of immune suppression . acute promyelocytic leukemia ( acute myeloid leukemia m3 ) is caused by translocation of reciprocal chromosomal rearrangement t(15;17 ) , which produces an oncogenic protein . we herein describe a 71-year - old man having cellulitis with leukocytopenia as a first sign of acute promyelocytic leukemia . dermatologists and hematologists should keep in mind that patients with a hematologic malignancy , such as acute promyelocytic leukemia , can develop cellulitis with leukocytopenia .

spare parts surgery means use of parts from non - salvageable digits in replantation or cross replantation ( amputated non - replantable digits used to reconstruct thumb ) . it is a well - established procedure in microsurgery . here , we present a case of harvesting double free flaps from an amputated non - replantable lower limb for the contralateral limb . this is based on the gillies principle , which states -do not throw away any tissue . this opportunity does not come very often in the clinical practice and one must be ready to grab it when it does ! to the best of our knowledge , there are a very few reported cases , where double free flaps from the amputated limb or digit has been used for spare parts surgery . a 45 year old male patient who was run over by a train resulting in a right leg amputation at the level of the knee and a crush injury of the left foot . the right lower limb had a severe comminution and bone loss at the knee joint , with the loss of skin and soft- tissue and crushing of muscle above and below the knee [ figures 1 and 2 ] . the left forefoot was completely degloved and all the toes were crushed and degloved as well [ figures 3 and 4 ] . amputated right lower limb right lower limb amputation stump crushed left foot - dorsal aspect crushed left foot - plantar aspect the right lower limb was deemed not replantable as the knee joint was severely damaged and not salvageable , in addition , debridement of crushed and devitalized tissues would result in a 15 - 20 cm shortening and a limb that was at least 15 cm short with fused knee joint would not be functionally useful and primary insertion of prosthetic knee joint was not considered to be feasible by the attending orthopaedic surgeon . focus was then shifted to the crushed left foot with a view to perform immediate debridement and early soft - tissue cover , to salvage as much of the foot as possible and get it fully healed and weight bearing at the earliest . stable and sensate skin cover were vital , as this would be the only surviving foot . a large defect such as this would require a large distant flap or even two flaps . best replacement for skin on the foot was anatomically identical skin from the opposite foot , which in this case was provided by the well - preserved amputated limb . the general condition of the patient was stable and he had no other life - threatening injuries . immediate double free tissue transfer from the amputated limb was done . a plantar flap based on the posterior tibial vessels [ figure 5 ] and a dorsal flap based on the dorsalis pedis vessels [ figure 6 ] , with the communication between the dorsal and plantar systems left intact through the deep branch of the 1 dorsal metatarsal artery . satisfactory inset of dorsal flap [ figure 7 ] , and of plantar flap [ figure 8 ] was achieved . post - operatively the patient developed a hematoma below the dorsal flap . since flaps were harvested from the amputated limb , small blood vessels that could not be seen were probably left unligated . re - exploration and evacuation of hematoma was performed . harvest of flap from plantar aspect harvest of flap from dorsum inset of plantar flap long - term follow - up - dorsal flap long - term follow - up - plantar flap for years surgeons have been amputating limbs at a higher level in limb crush injuries , to ensure good skin and soft - tissue cover for the stump and to make the stump more appropriate for prosthesis fitting . covering the stump with vascularised tissue using the microvascular techniques from another part of the body has now become common . in crush injuries of the foot , very often , early free tissue cover to replace the lost skin and soft - tissue can avoid an amputation . this will however require surgery on another part of the body , with additional trauma and scarring . spare parts surgery , transferring tissue from the amputated limb using microvascular techniques , is one step ahead because it uses tissue that would otherwise have been discarded , without any additional scarring and other such sequelae . since such opportunities are rare and have to be grasped immediately , we need to constantly be aware of this possibility and ready to use it to maximise patient benefit . if the patient is not haemodynamically stable , the harvested flap can be stored by wrapping in a saline soaked gauze in a sterile container and placing the container in a box of ice or cold water as per the same guidelines as for an amputated limb for replantation . recommended ischaemia times for reliable success with spare part surgery are parallel to that recommended in replantation i.e. , 12 h of warm and 24 h of cold ischaemia for harvesting flaps from amputated digits and 6 h of warm and 12 h of cold ischaemia for harvesting flaps from major amputations . use of skin preservation solutions to preserve the skin flaps has been tried in an animal model . furthermore occurrence of haematoma below the flap in spare part surgery is a realistic complication resulting from inability to achieve haemostasis during the harvest of the flap from an amputated achieving haemostasis is then a must after perfusion of the flap lest the flap bleeds after perfusion resulting in a haematoma post - operatively .

bilateral limb trauma poses many possibilities for management . in a situation of bilateral amputation , if the amputated limb is not salvageable or replantation is not advisable , the amputated limb can be used to harvest tissue for free tissue transfer to cover the amputation stump . we describe a case here in which we have used these principles .

during march 2010october 2011 , we conducted a nationwide survey of persons from all 3 zones in the country who had pulmonary sputum smear positive tb . the survey was designed according to the guidelines of the world health organization ( who ) ( 5 ) by using cluster sampling of 39 diagnostic centers . cases were classified as newly diagnosed or previously treated according to who definitions ( 6 ) . we collected the following variables through a questionnaire administered during sputum collection : patient sex , age , country of birth , and treatment history ( new or previously treated ) . a laboratory in south africa that is accredited for molecular testing by the national accreditation system tested sputum samples for resistance to rifampin and isoniazid by using genotype mtbdrplus assay ( hain lifescience gmbh , nehren , germany ) ( 7,8 ) . the sensitivity of this assay to detect mutations known to confer resistance is higher for rifampin than for isoniazid ( 98.4% vs. 88.7% , respectively ) . statistical analyses were performed in stata ( version 12 ; stata corp . , college station , tx , usa ) . prevalence estimates were adjusted for fluxes in tb notifications from 2007 , the year on which sampling calculations were based , through 2010 , the year in which the survey started ( table footnote ; technical appendix figure ) . * prevalence estimates were obtained by using logistic regression ( stata s svy : logit command , stata corp . , college station , tx , usa ) on the binary treatment history variable ; each new / retreatment case with a drug - susceptibility test result was weighted by the number of new / retreatment cases notified in its cluster in 2010 ( the year in which the survey started ) , divided by the total number of new / retreated cases with a drug - susceptibility test result in its cluster . the estimation of odds ratios reported elsewhere in the text also included the expansion of categorical sex , age group , and zone variables ( xi : logit ) , with clustering and cis of variance . the findings were robust to multiple imputation of missing data ( adding another 78 new and 18 retreatment cases to the sample ) , use of sampling weights based on 2007 notifications ( the year in which cluster samples were calculated ) , and no use of sampling weights at all ; prevalence estimates were equivalent to or slightly higher than those reported here . ninety - six enrollees were subsequently excluded because of sample contamination ( 52 patients ) , insufficient material to perform the genotype mtbdrplus assay ( 41 patients ) , and isolation of mycobacteria spp . the overall total drug susceptibility recovery rate was 89.9% , in line with the country expectations and who recommendations ( 5 ) . of the patients retained in the study ( 754 persons with new cases and 96 persons with previously treated cases ) , the male - to - female ratio was 2.4:1.0 , and median age was 30 years ( range 486 years , interquartile range 2344 years ) . mdr tb was detected in 5.2% ( 95% ci 2.87.5 ) of persons with newly diagnosed tb and 40.8% ( 95% ci 24.757.0 ) of persons with previously treated tb . levels of resistance to isoniazid and rifampin and frequencies of any resistance and monoresistance are shown in the table . history of previous anti - tb treatment was the strongest independent factor for mdr tb ( odds ratio [ or ] 23.0 , 95% ci 9.456.1 , p<0.001 ) , and living in the south - central region or in puntland was associated with a significantly higher risk for mdr tb than was living in somaliland ( or 3.6 , 95% ci 1.96.9 p<0.001 for living in puntland and or 4.3 , 95% ci 1.711.3 , p = 0.003 for living in the south - central region ) . associations between mdr tb and sex , age , and country of birth were not significant . compared with a study conducted in neighboring ethiopia in 2005 , where mdr tb was found in only 1.6% of new and 11.8% of previously treated tb cases ( 9,10 ) , and with surveys conducted in countries of the eastern mediterranean region , where the average proportion of mdr tb in new and previously treated tb cases was of 3.4% and 29.9% , respectively ( 4 ) , the proportions of mdr tb detected in somalia are high . at this level of resistance , one would expect that among the 9,760 pulmonary tb cases notified in somalia in 2011 ( 4 ) , 750 were mdr tb and therefore required treatment with second - line drugs ; this number does not include other ( non - mdr ) cases of rifampin - resistant tb that would probably require an mdr tb regimen . this finding presents a real emergency for the national tuberculosis control program considering the duration of second - line treatment ( > 2 years ) ( 11,12 ) , the current availability of such treatment in somalia for a only few patients , and the country s lack of laboratory capacity to diagnose drug resistance . a systematic review of the cost effectiveness of mdr tb care ( 13 ) suggests that it would cost us$3,5005,900 to treat mdr tb on an outpatient basis in somalia . at < us$400 per disability - adjusted life - year efforts are being made to treat mdr tb patients detected in the survey . because the cost of treating all 750 mdr tb patients is 32%54% of the us$8.2 million ( all of it from the global fund to fight aids , tuberculosis and malaria ) that was available to somalia in 2012 for its entire tb control program ( 4 ) , additional funding will be needed . in a drug quality survey conducted in somalia in 2010 , 60% of 10 products containing first - line anti - tb drugs that can be easily purchased from pharmacies and informal health care providers met international quality standards ( i. sindani , pers . the extensive use of drugs of suboptimal quality , the widespread practice of using wrong medical prescriptions , and incomplete adherence of patients to treatment are the most likely reasons for the high levels of mdr tb in somalia . these levels appear to be highest in the south - central region , where the security situation is most volatile and disruption of care more frequent . this region also is most affected by recent food shortages ( 14 ) and has the most internally displaced persons ( 15 ) , factors that are expected to exacerbate disease progression and transmission of m. tuberculosis . this study shows that nationwide surveys to monitor drug - resistant tb are possible even when social conditions are unstable . two middle eastern countries , afghanistan and yemen , also were able to conclude nationwide drug resistance surveys in 2011 despite social unrest ( 4 ) . sample collection , transportation , and monitoring of survey operations in our study have been challenging . the analysis had to account for population movements and changes in the availability of and access to health services . this study , conducted under difficult circumstances in a country with unstable social conditions , showed that mdr tb is a serious underdetected and widespread public health problem in somalia . the documented levels of mdr tb are among the highest reported in africa and the middle east and suggest that 750 patients in the country had mdr tb in 2011 . urgent measures should be introduced to improve access to diagnosis of drug resistance and availability of second - line medication for all patients who need them . percentage change in total tuberculosis notifications by diagnostic center participating in the survey , somalia , 20072010 .

in a nationwide survey in 2011 , multidrug - resistant tuberculosis ( mdr tb ) was found in 5.2% and 40.8% of patients with new and previously treated tb , respectively . these levels of drug resistance are among the highest ever documented in africa and the middle east . this finding presents a serious challenge for tb control in somalia .

to analyze nvt penicillin - nonsusceptible pneumococcus ( pnsp ) detected in patients with invasive pneumococcal disease , we used data from the active bacterial core surveillance ( abcs ) system , a population- and laboratory - based collaborative system between the centers for disease control and prevention and state health departments and academic institutions in 10 states ( california , colorado , connecticut , georgia , maryland , minnesota , new mexico , new york , oregon , and tennessee ) . we considered pnsp non - pcv13 serotypes detected in patients in all age groups from 2009 ( pre - pcv13 , n = 285 patients ) through 2012 ( post - pcv13 , 339 patients ) . nonsusceptibility was based on the meningitis breakpoint ( mic > 0.12 g / ml ) , as recommended by the clinical and laboratory standards institute ( 10 ) . / c were grouped together as 15bc because of the reported reversible switching between the 2 serotypes , which makes the precise differentiation of these serotypes difficult ( 11 ) . to determine whether geographic differences in the proportions of pnsp were consistent across serotypes , we calculated the proportions of pnsp for each of the 7 most common nvt serotypes ( 15a , 15bc , 16f , 23a , 23b , 33f , and 35b ) across the 10 sites for 2009 and 2012 . we found that serotypes with the highest proportions of pnsp in 2012 already had high resistance in 2009 ( figure 1 ) . we calculated the spearman correlation coefficient between the proportion of pnsp for each pair of serotypes across states in 2009 ( range 0.09 to 0.66 ) and 2012 ( range 0.300.79 ) ( technical appendix ) . we found significant overall correlation in 2009 and 2012 ( p<0.001 for both years ) , indicating that sites with high proportions of pnsp in 1 serotype typically will also have high proportions of pnsp in other serotypes . this finding suggests that differences in selection pressure account for the geographic variation in the proportions of pnsp . comparison of proportion of nonvaccine type serotypes with penicillin resistance , by serotype , united states , 2009 and 2012 . based on active bacterial core surveillance system data from 10 us states . we next implemented a standardized regression approach , used previously to analyze the pneumococcal - resistance patterns pre - pcv7 ( 7 ) and post - pcv7 ( 8) ( technical appendix ) . to investigate the source of geographic variation in the proportion of pnsp , we tested the hypotheses that either geographic heterogeneity in serotype distribution ( std1 ) , or serotype - specific differences in penicillin resistance ( std2 ) were responsible for the observed variation . these effects were quantified by regressing crude versus standardized prevalence of penicillin resistance ( figure 2 ; technical appendix ) , by which a regression slope of 1 would indicate that the factor considered had zero effect . by using 2009 data , we found that regression slopes for std1 ( 0.445 , 95% ci 0.083 to 0.972 ) and std2 ( 0.463 , 95% ci 0.013 to 0.939 ) indicate that both factors played a similar intermediate role in generating this geographic variation in penicillin resistance , with neither 95% ci containing 1 . in 2012 , the regression coefficient for std2 was higher ( 0.634 , 95% ci 0.141.128 ) , whereas the coefficient for std1 decreased ( 0.367 , 95% ci 0.025 to 0.758 ) . although these changes are not statistically significant relative to 2009 , they might suggest shifting contributions to the observed variation in proportions of pnsp after the introduction of the pcv13 vaccine in 2010 , with geographic differences in serotype distribution having an increased role and differences in serotype - specific pnsp becoming less important . crude versus standardized proportions of nonvaccine type serotypes with penicillin nonsusceptibility , by state , united states , 2009 and 2012 , based on active bacterial core surveillance system data from 10 us states . regression slopes with 95% cis are indicated in the upper left corner of each panel . dashed lines represent the inverse - variance weighted ( red ) and unweighted ( gray ) regression slopes . finally , we sought to quantify the rate of change in penicillin resistance during 20092012 in each state . we documented the proportion of pnsp by state for the pre- and post - pcv13 periods ( technical appendix table 4 ) . new mexico , maryland , and georgia saw the highest increases in the proportion of pnsp during 20092012 , whereas a slight decline was observed for colorado , new york , and connecticut . although the distribution of serotypes might greatly fluctuate among geographic regions immediately after vaccine introduction , the overall proportions of nvt serotypes with penicillin resistance across the country might not vary significantly between the pre- and post - vaccine periods . of potential importance are the small increases in the proportions of pnsp serotypes not included in either vaccine that were observed between the implementation of pcv7 and pcv13 ( 12 ) , which might lay the foundation for changes post - pcv13 . the marked variation in the proportion of penicillin resistance among states highlights the potential of local selective pressures to favor certain serotypes and resistant strains within each serotype to increase in frequency as the population returns to equilibrium ( 13 ) . previous studies have already shown significant regional differences in antibiotic use and vaccination coverage across the united states ( 14,15 ) . a combination of these factors , which will likely vary between and within regions , would greatly affect proportions of resistance across the country . in our study , we observed that the dynamics of penicillin resistance continue to shift in the wake of vaccine introduction . our postvaccine observations were recorded shortly after the introduction of the vaccine ; additional observations would be valuable to determine the stability of the postvaccine dynamics and any potential importance of the temporal changes we observed to factors contributing to variation in resistance levels . further long - term nationwide surveillance of serotype dynamics is required to assess the multiple ecologic factors that influence antibiotic resistance in the pneumococcus in the conjugate vaccine era . methods and additional results for a study assessing penicillin resistance of nonvaccine type pneumococcus before and after pcv13 introduction , united states .

introduction of 13-valent pneumococcal conjugate vaccine in the united states was not associated with a significant change in prevalence of penicillin resistance in nonvaccine type serotypes because of the variable success of highly resistant serotypes . differences in regional serotype distribution and serotype - specific resistance contributed to geographic heterogeneity of penicillin resistance .

hyperpigmentation of the gingiva has always been a concern to certain patients , especially young females . although melanin pigmentation of the gingiva is completely benign and does not present a medical problem , its unaesthetic appearance as black gums is more pronounced in patients having a high smile line ( gummy smile ) . gummy smile can be due to incomplete passive eruption , maxillary protrusion , hyperactive muscle of lips , short lip , gingival enlargement , etc . gingival depigmentation can also be performed by surgical blade , coarse diamond bur , electrosurgery , cryosurgery or lasers . considering the advantages of lasers over other modalities of treatment , this article will focus on the management of such a case using gaalas diode lasers of 810 nm . a 22-year - old female patient was referred with a complaint of gummy smile and hyperpigmented gingiva [ figure 1 ] . on examination , pseudopockets ( approximately 23 mm ) were detected in the maxillary and mandibular anteriors along with generalized excessive amount of melanin pigmentation on the gingiva [ figure 2 ] . the patient was explained about the treatment options and informed that , after depigmentation , melanin pigmentation tends to recur and , as gingivectomy is also performed simultaneously , the overall appearance would be worth doing it . profile view of gummy smile with hyper melanin pigmentation of the gingiva intraoral view of gummy smile with hyper melanin pigmentation of the gingiva gingivectomy and depigmentation were planned in the 1525 region and the 3444 region using a 810 nm diode laser . although procedures like this can be performed under topical anesthesia , infiltration was planned as the patient was anxious and sensitive . under infiltration anesthesia with 2% lignocaine ( with 1:100,000 adrenaline ) , an 810 nm gaalas diode laser ( picasso)*(picasso , by amd lasers ) was used in contact mode with the gingival tissues . e gel was prescribed for local application -three to four times a day for 2 days . because a large area of the raw wound was kept exposed , antibiotic cap . immediate postoperative view of gingivectomy and depigmentation using an 810 nm diode laser the patient reported no adverse effects or discomfort during the postoperative healing phase . she was happy and satisfied with 6-month postoperative results [ figures 4 and 5 ] . gingivectomy and depigmentation were planned in the 1525 region and the 3444 region using a 810 nm diode laser . although procedures like this can be performed under topical anesthesia , infiltration was planned as the patient was anxious and sensitive . under infiltration anesthesia with 2% lignocaine ( with 1:100,000 adrenaline ) , an 810 nm gaalas diode laser ( picasso)*(picasso , by amd lasers ) was used in contact mode with the gingival tissues . e gel was prescribed for local application -three to four times a day for 2 days . because a large area of the raw wound was kept exposed , antibiotic cap . immediate postoperative view of gingivectomy and depigmentation using an 810 nm diode laser the patient reported no adverse effects or discomfort during the postoperative healing phase . she was happy and satisfied with 6-month postoperative results [ figures 4 and 5 ] . diode laser is a versatile laser and has been successfully used at three wavelengths : 980 nm , 810 nm and , more recently , 940 nm . it has numerous soft tissue applications , viz frenectomy , crown lengthening , gingival depigmentation , troughing , etc . in a diode laser , the substance stimulated to produce a coherent light beam is a semiconductor . this technology has produced a laser that is compact and economic . a diode laser has become an important tool in the dental armamentarium due to its exceptional ease of use and affordability . the diode laser is well absorbed by melanin , hemoglobin and other chromophores that are present in periodontal disease . this provides the diode laser with broad clinical utility : it cuts precisely , coagulates , ablates and vaporizes the target tissue with much less trauma , improved postoperative healing and faster recovery time . melanin pigmentation in gingiva is present only when melanin granules synthesized by melanocytes are transferred to the keratinocytes . therefore , recurrence of the pigmentation is inevitable and has been reported from 24 h to 8 years following surgery . conventional procedures for corrections of pigmented gingiva consist of surgical stripping with scalpel , use of electrosurgery , cryosurgery or a coarse diamond bur . however , the laser is the least - invasive and predictable method of performing this procedure . it has a high level of precision , requires minimal anesthesia and causes very low collateral tissue damage . cases where only gingivectomy is required can be performed without anesthesia or under topical anesthesia , but because both gingivectomy and depigmentation were planned together in this patient and a significantly larger area needs to be operated upon , infiltration anesthesia was given . given the incredible ease of use and its versatility in treating soft tissue , the diode laser becomes the patients with complaints of hyperpigmented gingiva should also be assessed for the presence of gummy smile . once the amount of gingiva displayed is reduced by gingivectomy , the patient 's concern for hyperpigmented gingiva will also reduce . as a result , in most of the cases , a repeat surgery for depigmentation

hyperpigmentation of gingiva becomes more pronounced if it is associated with gummy smile . correction of gummy smile and depigmentation together are key to complete patient satisfaction . an 810 nm ( 1.5 w , pulsed ) gaalas diode laser was used to achieve the desired results in a 22-year - old female patient . the 6-month follow - up results showed excellent color and contour of the gingiva . mere depigmentation without correcting gummy smile may look cosmetically good but esthetically unacceptable . diode laser was used as it is known to be an excellent tool as compared with other conventional surgical procedures in terms of patient and operator comfort .

carcinosarcoma ( also known as pseudosarcoma , pseudosarcomatous squamous cell carcinoma , pleomorphic carcinoma , and spindle cell carcinoma ) is a highly malignant tumor characterized by dual malignant histologic differentiation of the epithelial component consisting of a focally squamous cell carcinoma and a mesenchymal component having a sarcomatoid stroma . carcinosarcoma may arise in any squamous epithelium of the body , however its occurrence is extremely rare in the sinonasal cavity [ 3 - 13 ] . we present a case of a carcinosarcoma located in the maxillary sinus that was is aggressive and displayed a high recurrence rate even when a multimodality therapeutic approach was adopted . a 62-year - old male was admitted to the emergency room due to uncontrolled epistaxis and complaining of swelling and tenderness in the right cheek . the patient was receiving warfarin as an anticoagulative measure , having previously suffered a stroke . an examination of the nasal cavity was not possible at the emergency room due to the severity of bleeding . two days later , when the nasal packing was removed and endoscopic examination performed , a mass in the middle meatus and bulging of the medial wall of the maxillary sinus were observed ( fig . computed tomography ( ct ) and magnetic resonance imaging ( mri ) scans revealed a large mass comprised of soft tissue with an ill - defined outline and an irregular peripheral enhancement on the right maxillary sinus . the mass had pushed against the right inferior wall of the maxillary sinus ; destroyed the infraorbital foramen ; completely destroyed the medial wall of the maxillary sinus ; partially damaged the superior , middle and inferior turbinate ; and obstructed the entire right nasal cavity . the lateral , anterior , and inferior walls of the right maxillary sinus were focally destroyed and a focal tumor extension was exposed . the mass extended superiorly to some part of the ethmoid sinus but did not involve the sphenoid sinus and frontal sinus ( fig . an endoscopic biopsy revealed a carcinosarcoma with an osteosarcomatous element by hematoxylin - eosin staining and immunohistochemical stain ( fig . 2 ) . fluorodeoxyglucose positron emission tomography ( fdg pet)-ct was used to evaluate metastasis to adjacent organs . fdg pet - ct revealed the presence of large mass of soft tissues with increased fdg uptake accompanied by bony erosion in the right maxillary sinus . also , nodular lung lesions with increased fdg uptake in lateral basal and posterior basal segment of right lower lung were observed . hence , the clinical tnm staging of this patient was t3n0m0 ( stage iii ) . a surgical resection with postoperative chemoradiation therapy was planned and the patient underwent a total maxillectomy on the right side . examination in the operating room revealed a large tumor filling the nasal cavity , maxillary sinus , and ethmoid sinus . the tumor had eroded through the inferior and medial orbital walls , however , periorbital invasion was not evident . the patient 's postoperative course was uncomplicated , and he received postoperative radiation therapy with a total dose of 5,580 cgy . however , during the radiation therapy , a mass lesion in the periorbital area was found in an endoscopic examination . as a consequence , wide local excision was performed on the mass and the patient received a full course of irradiation , followed by chemotherapy ( cisplatin+5 fluorouracil+taxotere ) . two months later , the patient developed a massive recurrence infiltrating the orbit , cheek , and the masseter muscle . the patient decided not to receive further surgical treatment or chemotherapy , and was lost to follow - up . carcinosarcoma is a biphasic tumor composed of dual components : an epithelial portion with squamous cell carcinoma and sarcomatoid lesion . this tumor can arise in any squamous epithelium of the body , such as the respiratory tract , upper aerodigestive tract , and reproductive organs . in the head and neck region , this tumor is extremely rare in the sinonasal cavity , as indicated by the few case reports available ( table 1 ) [ 3,5 - 13 ] . because of this rarity , tumor histogenesis , clinical course and resulting prognosis , and management are contentious issues . concerning histogenesis , whether the cellular composition of carcinosarcoma is that of a true heterologeous tumor or whether it originates from a single malignant component having both epithelial and mesenchymal differentiation is debatable . recent electron microscopic and immunohistochemical investigations revealed epithelial differentiation in some of the spindle cells in the sarcomatous element , suggesting that the sarcomatous element is derived from mesenchymal transformation of the carcinoma cells . from the known cases ( table 1 ) , carcinosarcoma of the maxillary sinus seems to preferentially appear in older patients . clinically , the symptoms are often nonspecific , but unilateral nasal obstruction and bleeding are initial symptoms . because of the high stage presentation at the time of diagnosis , this tumor presents significant therapeutic challenges and a fateful prognosis for the patient . carcinosarcoma in the maxillary sinus was treated by surgery in eight of the 11 cases ( table 1 ) . except for one case , but , clinical effectiveness of chemotherapy is impossible to determine with statistical significance due to the small number of cases to date . although an accurate estimation of survival outcome is not conclusive , carcinosarcoma at the maxillary sinus confers a poor survival rate and a high local recurrence rate . in the known cases , tumors in the maxillary sinus recurred after management in seven of 11 cases ( table 1 ) . local recurrences and metastases typically were lethal . an overall mortality rate of 42% at 30 months was reported in carcinosarcoma at other sites . survival periods were from 2 - 40 months and local recurrences eventually occurred in most cases ( table 1 ) . when a carcinosarcoma tumor is located within the maxillary sinus , multimodal therapy ( i.e. , surgery , radiotherapy , and/or chemotherapy ) should be considered . also , before aggressive multimodal therapy is initiated , patients should be counseled concerning the tendency for aggressive patient behavior , poor prognosis , and likelihood of recurrence .

carcinosarcoma is a highly malignant tumor characterized by dual malignant histologic differentiation of epithelial and mesenchymal components . the tumor is extremely rare in the sinonasal tract . we report a case of a 62-year - old man with carcinosarcoma involving the maxillary sinus .

midgut malrotation ( mmr ) is a congenital nonrotation or incomplete rotation of the primitive intestinal loop around the axis of superior mesenteric artery ( sma ) during fetal development . mmr is more known by pediatrics than adult surgeons because it occurs at a rate of about 1 in 500 live births . up to now , surgical treatment has been guided by the experience from pediatric surgery and ladd 's procedure has been the treatment of choice in adults . however , a dilemma arises when patients are asymptomatic and incidentally diagnosed with mmr during another abdominal affection such as appendicitis . volvulus is the main complication of mmr , but the occurrence of acute midgut volvulus of clinical significance in the absence of surgical treatment is unknown . therefore , practicing ladd 's procedure on asymptomatic patients may put them at risk of complications . here , we report the case of a 37-year - old patient with acute left side appendicitis and asymptomatic mmr . a 37-year - old man was admitted at the emergency unit of our hospital with acute abdominal pain , which started the previous night . pain was diffused , with tenderness mainly in upper left quadrant , and the temperature was 37.5c . laboratory tests showed an elevated blood cell count ( 15,000 ) with normal c - reactive protein . contrast - enhanced abdominal computed tomography showed acute left side appendicitis with midgut malrotation [ figure 1a - c ] . appendix was enlarged , with a transverse diameter measured to 13 mm , associated with four stercoliths visualized in the plane of the left renal vein . the entire small bowel was found in the left half of the abdomen and the entire colon was found in the right half . the superior mesenteric vein ( smv ) was to the left of the sma rather than in the normal right ventral position . surgical findings confirmed the severe inflammation of the appendix and the ileocecal region(s ) located in the left quadrant . a ladd 's procedure was performed , including derotation of the bowel , appendectomy , division of the mesenteric bands lying across the duodenum from cecum to right upper quadrant , widening of the base of the mesentery , taking down the ligament of treitz , moving the duodenum to the right , and finally returning the bowel to a position of nonrotation with the cecum placed into the left upper quadrant [ figure 1d ] . superior mesenteric vein ( arrow ) is on the left side of the superior mesenteric artery ( arrowhead ) ; ( b ) coronal multiplanar reformation ( mpr ) from portal - venous phase ct demonstrates a midgut malrotation . superior mesenteric vein ( black arrowhead ) is on the left side of the superior mesenteric artery ( white arrowhead ) . the entire small bowel ( thin arrows ) is in the left half of the abdomen and colon ( thick arrows ) is in the right half ; ( c ) coronal mpr from portal - venous phase ct demonstrates a acute upper left side appendicitis ( arrows ) with two stercoliths ( arrowheads ) and ( d ) operative view with the entire small bowel in the right half of the abdomen and colon in the left half left side acute appendicitis is extremely rare but can occur with congenital abnormalities with true left - sided appendix such as situs inversus totalis and mmr or as an atypical presentation of a long right - sided appendix , which is thus projected into the left lower quadrant . mmr is a congenital anomaly referring to either nonrotation or incomplete rotation of the primitive intestinal loop around the axis of the sma during fetal development . adult mmr is rare because the diagnosis is usually made before the age of 1 year . the most dreaded complication of mmr is volvulus , which occurs in 60 - 70% of neonates diagnosed with mmr and delay in diagnosis may lead to extended intestinal necrosis . diagnosis is made in the adult in the presence of chronic abdominal symptoms , during surgery for acute abdomen , or incidentally during an imaging exam for no specific symptoms . in the case of our patient , this exam should show the whirlpool sign , which is wrapping of smv and bowel around the sma . adult mmr is rare with an incidence ranging from 0.0001 to 0.19% in asymptomatic adults . the problem is to know whether it is necessary or not to treat asymptomatic mmr . some authors have advocated operative management only in patients with mmr symptoms because they found that patients had a low risk of complication and elective surgery was not necessary with close follow - upb)second , performing appendectomy and ladd 's procedure in the same time , to treat mmr and avoid complications . for some authors the risk of volvulus , even if low , warrants operative intervention especially since the risk for volvulus is lifelong and do not diminish with age . actually , the current literature supports surgical correction of mmr for patients with minor symptoms or incidentally found mmr because very few of these patients are truly asymptomatic if careful history is obtained . in our case , this attitude is supported because of a difficult follow - up . some authors have advocated operative management only in patients with mmr symptoms because they found that patients had a low risk of complication and elective surgery was not necessary with close follow - up second , performing appendectomy and ladd 's procedure in the same time , to treat mmr and avoid complications . for some authors the risk of volvulus , even if low , warrants operative intervention especially since the risk for volvulus is lifelong and do not diminish with age . actually , the current literature supports surgical correction of mmr for patients with minor symptoms or incidentally found mmr because very few of these patients are truly asymptomatic if careful history is obtained . in our case , this attitude is supported because of a difficult follow - up . the complication of surgical management of mmr is bowel obstruction secondary to adhesion after ladd 's procedure . in a pediatric series , several studies of retrospective series have shown that laparoscopic treatment of mmr is feasible in most cases , with good perioperative outcome , but there is still a lack of long - term follow - up with this method . benefits of laparoscopic surgery were : less pain , early return of bowel function , and shorter hospital stay with a decrease in the incidence of postoperative adhesion possibly translating into a lower incidence of postoperative bowel obstruction . according to literature , most patients are operated by laparotomy and only a few by a laparoscopic approach . management of incidentally mmr diagnosis during another abdominal affection can be either conservative or not . the watch and wait attitude could be proposed if the patient could be followed , otherwise the surgical attitude should definitively be proposed .

midgut malrotation ( mmr ) is a congenital anomaly referring to either nonrotation or incomplete rotation of the primitive intestinal loop around the axis of the superior mesenteric artery during fetal development . adult mmr is rare and majority of mmr in adults remains asymptomatic throughout life . the increasing use of diagnostic imaging for acute abdominal pain will lead to more incidental recognitions of mmr . up to now , surgical treatment has been guided by the experience from pediatric surgery , and ladd 's procedure has been the treatment of choice in adults with mmr . however , a major dilemma arises when patients are essentially asymptomatic and incidentally diagnosed with mmr during another abdominal affection like acute appendicitis . the surgeon has to decide whether it is necessary to also treat the mmr . here , we report a rare case of a 37-year - old patient with acute left side appendicitis in association with asymptomatic mmr . we discuss whether correction of the asymptomatic malrotation was indicated .

to present a unique case of a 58-year - old female with toxic anterior segment syndrome ( tass ) , following a triple procedure : descemet 's stripping automated endothelial keratoplasty ( dsaek ) , phacoemulsification and posterior chamber intraocular lens implantation . the patient was treated with topical dexamethasone sodium phosphate 0.1% and topical atropine sulfate 1% . due to a slow improvement in her clinical status , oral prednisone 1 mg / kg / day was added . the anterior chamber reaction improved gradually , with tapering down of topical and oral treatment , until a complete resolution of the anterior chamber reaction was observed . taking into account the estimated volume of dsaek triple procedures performed worldwide , we would expect an annual incidence of several tass cases , following triple dsaek procedures . however , we were unable to find any such previous reports in the literature . this fact raises questions regarding the cause of reduced tass incidence following triple dsaek procedures . toxic anterior segment syndrome ( tass ) is an acute , sterile anterior chamber inflammation , which may develop following anterior segment surgery . most cases are reported after uneventful cataract surgery . in patients requiring both cataract extraction and endothelial keratoplasty , a descemet 's stripping automated endothelial keratoplasty ( dsaek ) triple procedure , consisting of phacoemulsification and intraocular lens ( iol ) implantation , followed by dsaek , up to the present , only two reports of keratoplasty - related tass have been published , both following penetrating keratoplasty . the first was a case series of 8 patients with tass - like , noninfectious , severe , early inflammation . the second , reported a large outbreak of tass ( 24 cases out of 94 procedures performed ) , presenting as postoperative keratitis with inflammatory anterior chamber reaction mainly hypopion and cells . this outbreak was found to be caused by faulty sterilization of the guided trephine system . to our knowledge herein is presented a case of tass following a triple procedure : dsaek , phacoemulsification and posterior chamber iol implantation . a 58-year - old female , suffering from bilateral fuchs endothelial dystrophy , bilateral cataract and corneal subepithelial scarring in her left cornea , following an adenovirus infection , underwent an uneventful dsaek triple procedure in her left eye : phacoemulsification , implantation of a posterior chamber iol and dsaek . intraocular pressure was 13 mm hg , best - corrected visual acuity was 20/200 , and the graft was attached to the recipient cornea , with a deep anterior chamber . treatment with topical dexamethasone sodium phosphate 0.1% and ofloxacin 0.3% administered four times daily was initiated . five days following the surgery , the patient presented with decreased vision in her left eye , which had begun 24 h postoperatively . on examination of her left eye , 1 ) revealed conjunctival hyperemia , a completely attached and centrally located endothelial corneal graft , deep anterior chamber with a cellular reaction of 3 + and prominent flare measuring 3 + . visualization of the posterior segment was poor due to the clinical status of the anterior segment no details could be observed , but for a red light reflex . the patient was started on hourly topical dexamethasone sodium phosphate 0.1% . due to the extensive posterior synechiae , the patient received a short and intensive course of topical tropicamide 0.5% and phenylephrine hydrochloride 10% , followed by topical atropine sulfate 1% . follow - up examination , one day after the initiation of treatment , revealed significant improvement in the anterior chamber cellular reaction with no evident cells or flare , and residual posterior synechiae spanning 60 degrees . the posterior segment could be well visualized , showing no inflammatory involvement of the retina and vitreous . fibrin fiber accumulation was only mildly improved and therefore , the patient was started on oral prednisone 1 mg / kg / day . due to the early onset of visual deterioration ( 24 h postoperatively ) , the normal appearing posterior segment ( visualized shortly after initiation of treatment ) and the rapid clinical response to the above treatment , a clinical diagnosis of infectious endophthalmitis was ruled out . follow - up examinations on days 3 , 8 and 10 following initiation of treatment , revealed gradual absorption of fibrin and no evident posterior synechiae . 8 weeks following the tass diagnosis , the patient 's best - corrected visual acuity was 20/50 , with a spherical correction of + 1.25 diopter and a cylindrical correction of 1.75 diopter ( 170 axis ) . intraocular pressure was 14 mm hg , with a clear , attached , thin endothelial corneal graft . no evidence of an anterior chamber reaction , fibrin formation or posterior synechiae was observed . according to the eye bank of america association , 42,606 corneal transplants were performed in the usa in 2009 , out of which 18,221 were endothelial keratoplasty procedures ( 2009 eye banking statistical report , washington , dc , eye bank association of america ) . the world health organization ( who ) estimates that about 120,000 corneal transplants are performed worldwide each year ( human organ and tissue transplantation report by the secretariat , submitted at the 112th session of the world health organization executive board , may 2003 ) . there is no sufficient data in the literature regarding the volume of triple dsaek procedure surgeries performed worldwide . the frequency of tass reported in the literature is about 0.250.8% [ 5 , 6 ] . therefore , we would expect an annual incidence of several tass cases , following triple dsaek procedures . it is probable that the cataract extraction constituent of the triple dsaek procedure is responsible for the occurrence of tass in our patient . nevertheless , the fact that there is no previous report of tass following such a procedure raises questions regarding the cause of the reduced incidence of tass following triple dsaek procedures . due to the fact that the inflammatory reaction may jeopardize the integrity of the endothelial graft and reduce the chances of a successful transplant , we intend to closely monitor this patient and apply a more gradual tapering down of her current treatment .

purposeto present a unique case of a 58-year - old female with toxic anterior segment syndrome ( tass ) , following a triple procedure : descemet 's stripping automated endothelial keratoplasty ( dsaek ) , phacoemulsification and posterior chamber intraocular lens implantation.methodsthe patient was treated with topical dexamethasone sodium phosphate 0.1% and topical atropine sulfate 1% . due to a slow improvement in her clinical status , oral prednisone 1 mg / kg / day was added.resultsthe anterior chamber reaction improved gradually , with tapering down of topical and oral treatment , until a complete resolution of the anterior chamber reaction was observed.conclusionstaking into account the estimated volume of dsaek triple procedures performed worldwide , we would expect an annual incidence of several tass cases , following triple dsaek procedures . however , we were unable to find any such previous reports in the literature . this fact raises questions regarding the cause of reduced tass incidence following triple dsaek procedures .

aura is defined as attacks of reversible focal neurological symptoms ( visual , sensory and/or speech symptoms ) that last more than 5 min and no longer than 1 h. migraine - like headache usually occurs at the onset , during or follows aura symptoms . patients with motor weakness , according to the present classification , are classified separately as hemiplegic migraine . it is well known that physical activity can lead to an aggravation of the intensity of the headache and a primary exertional headache is described in the current ihs classification under other primary headaches as a migraine - like headache unleashed by physical exertion . we describe the cases of three patients with recurrent episodes of migraine with aura induced by physical activity . the relationship between exertion and aura is unknown and still debated ; moreover , the international classification of headache does not , at present , include this subtype of headache . three young men ( case a 19 year - old , case b 21 year - old , case c 25 year - old ) came to our observation for recurrent attacks of migraine - like headache of a pulsating quality and severe intensity , with nausea , photo- and phonophobia , that resolved spontaneously within 12 h if untreated . the attacks were preceded by reversible visual symptoms presenting as fortification spectrum and ipsilateral cheiro - oral paresthesia ( cases b and c only ) , that lasted for 1540 min . onset of the symptoms occurred a few years earlier : 4 years for cases a and c , 2 years for case b. in all cases the symptoms occurred when they were in the locker room : in cases b and c shortly after a football match , but never after training ; whilst in case a the symptoms occurred occasionally after swimming pool and gym training or after participating in physical education activities at school . the father of case a and the mothers of cases b and c suffered from episodic attacks of migraine without aura . the patients medical history , physical and neurological examination did not suggest any other secondary disorder ( cases a and b are smokers ) . case a also suffers from episodic migraine without aura according to the current international classification of headache disorders ( ichd - ii ) criteria . the patients , however , underwent extensive diagnostic investigation : brain magnetic resonance with angiographic sequences , electroencephalography , vertebral and carotid echo - doppler , complete ocular examination , electrocardiography , transthoracic echocardiography and complete blood cell count , general chemistry profile , coagulation studies , protein c , protein s , antithrombin iii , anticardiolipin antibody , erythrocyte sedimentation rate , c - reactive protein , antinuclear antibody and thyroid function test . the prevalence of sport- and exercise - related headaches is estimated to be about 3035% ( 15% of which are migrainous headaches ) [ 2 , 3 ] . in the study of williams and nukada , the reported subtypes of headache were : effort migraine , trauma - induced migraine , effort / exertion headache and post - traumatic headache ; all effort and trauma - triggered migraine patients ( 11 and 8 , respectively , of 129 patients ) reported aura symptoms before the headache ( visual and/or sensory disturbances ) . however , the precise epidemiology of this phenomenon is unknown . according to ichd - ii criteria , the headache subtype presented by the patients fulfilled criteria for typical aura with migraine headache ( ichd - ii code : 1.2.1 ) and for primary exertional headache ( pulsating headache , lasting from 5 min to 48 h , brought on by and occurring only during or after physical exertion ; ichd - ii code : 4.3 ) . since these symptoms could mimic , in approximately 10% of these headaches , important pathologies , such as carotid dissection , artero - venous malformation , cerebral venus sinus thrombosis , seizures , subarachnoid or intraparenchymal haemorrhage , it was therefore mandatory to exclude a secondary form of headache in these patients . there are anecdotal reports of episodes of migraine preceded by head trauma and visual symptoms ( with a past history of non - sports - related migraine ) , migraine prodrome symptoms after unusually strenuous running with no subsequent head pain or recurrent attacks of hemiplegic migraine induced only by exertion . to date , the pathogenesis of primary exertional headache is unidentified and it is still under debate ; several theories regarding the cause have been proposed , such as , migraine triggered by physical effort particularly evident in aerobic exercise , altitude and hot weather , suggesting that low oxygen tension may trigger migraine by an as yet unknown mechanism . moreover , it has been postulated that a dilatation of pain - sensitive venous sinuses , at the base of the brain , as a result of increased cerebral arterial pressure , is induced by the exertion . in contrast to the hypothesized pathophysiology of the cough headache ( ichd - ii code : 4.2 ) , a similar vascular and hemodynamic pathogenesis is supposed to be shared by both primary exertional headache and primary headache associated with sexual activity ( ichd - ii code : 4.4 ) , due to the similar age at onset , male predominance , pain characteristics and response to treatment . the pathophysiological correlate of migraine aura is cortical spreading depression ( csd ) . in our patients it has been suggested that the combination of exertion - induced hyperventilation and the subsequent hypocapnia with respiratory alkalosis and hypomagnesemia predisposes these patients to cerebral vasoconstriction during exertion lowering the threshold for the development of csd or aura in migraineurs . the present ichd - ii classification does not mention sport / exercise - induced migraine with aura episodes as primary headache , although there are many reports of attacks of migraine with aura shortly after practicing . therefore , in case of patients suffering from this particular type of headache , there is currently the need to make a double diagnosis ( typical aura with migraine headache and primary exertional headache ; ichd - ii codes : 1.2.1 and 4.3 ) , or to add a specifier ( e.g. migraine with aura triggered by exercise ) . since there are many cases described in the literature of migraine with aura triggered only by exercise , to faciliate the diagnosis it may be helpful to specify , in the typical aura with migraine headache comments , that in some cases it can be exclusively triggered by sport / exercise .

it is well known that physical activity can aggravate the intensity of the headache , but the pathophysiological relationship between exertion and aura is still unknown . anecdotal reports describe episodes of migraine preceded by head trauma and visual symptoms , migraine prodrome symptoms after unusually strenuous running with no subsequent head pain or recurrent attacks of hemiplegic migraine induced only by exertion . we describe the cases of three young men with recurrent episodes of migraine with aura occurring in the locker room shortly after a football match . since the symptoms could mimic important pathologies in approximately 10% of these of headaches , it was mandatory to exclude a secondary form of headache in these patients . several theories exist regarding the cause of primary exertional headache , but the pathogenesis of migraine triggered by physical activity has still not been identified . the present international classification of headache disorders does not mention sport / exercise - induced migraine with aura episodes as primary headache . since there are many cases described in the literature of migraine with aura triggered only by exercise , it may be helpful to specify , in the typical aura with migraine headache comments , that in some cases it can be exclusively triggered by sport / exercise .

an hiv - negative male , in his sixties , originally presented with a 6-month history of an isolated large nodule on the right malleolar region which was confirmed as kaposi 's sarcoma ( ks ) on excision . subsequently he continued to develop more papules and plaques on the feet and over the following 7 years underwent excision of around 20 skin lesions under local anaesthesia . more recently he developed , simultaneously , a crop of 5 nodules and a large plaque of ks 5.5 cm in diameter on the dorsum of the right foot with extension to the interdigital spaces and toes ( fig . 1a , fig . chemotherapy with intravenous liposome - encapsulated doxorubicin was not considered because of the significant comorbidities including mild to moderate heart failure . therefore , in the following order , we tried two courses of photodynamic therapy , imiquimod 5% cream applied once daily for 8 weeks and a cycle of anti - herpes therapy based on valganciclovir . it was decided to administer intralesional vinblastine 1 mg / ml diluted 1:5 with saline solution . however , the patient developed side effects such as general malaise , swelling and erythema of the perioral and periocular areas and tingly tongue after the first injection , in keeping with a possible allergic reaction . at that point , at a bit of a loss for options , we switched to doxorubicin . following a serial dilution test from 1:20 to undiluted , this medication was used intradermally at the dose of 2 mg / ml diluted 1:1 with saline solution . the large ks plaque on the dorsum of the right foot was treated by spacing the intradermal injections every 5 mm , using a similar technique to that used in the treatment of axillary hyperhidrosis with botulinum a toxin . the treatment led to complete resolution of the ks lesions after 4 treatments spaced 6 weeks apart . we observed skin necrosis in some well - delimited areas following each injection ( fig . 1b ) , associated with mild to moderate pain which was well controlled with paracetamol 1,000 mg twice daily . the patient has not developed any new lesions for almost 18 months and continues to remain clear ( fig . ks is an angioproliferative disease associated with human herpesvirus 8 . the classic variant of ks is characterised by a low mortality and significant morbidity , and treatment needs to be finely balanced between these two aspects . to date , a curative treatment has yet to be found and therapeutic management includes surgery , radiotherapy , chemotherapy or a combination of all of the above . although in recent years numerous agents such as thalidomide , imatinib , sirolimus as well as matrix metalloproteinase inhibitors ( col-3 ) , anti - angiogenic factors ( bevacizumab ) and nf-b inhibitors ( bortezomib ) have been tried , the outcome of these treatments remains unsatisfactory . liposomal anthracyclines ( pegylated or liposomal daunorubicin or doxorubicin ) and taxanes such as paclitaxel therefore remain the cornerstones of systemic therapy against ks . doxorubicin acts through intercalation of double - stranded dna bases and by inhibiting dna topoisomerase ii whose activity is markedly increased in proliferating cells . it represents a particularly effective treatment for widespread ks as it accumulates in highly vascularised lesions . common agents for intralesional use in ks include interferon alpha , and more recently vincristine and vinblastine . although intralesional doxorubicin is a standard treatment for ks in some centres , there are no publications showing the effectiveness of this treatment in ks . intralesional doxorubicin was very successful in this case and the persistent remission induced would suggest that doxorubicin might be equally or even more effective than other standard intralesional treatments for ks cutaneous lesions in selected cases . further studies with a large cohort of patients could be helpful to clarify the impact of intralesional doxorubicin in ks .

classic kaposi 's sarcoma ( ks ) is a disease with low mortality but high morbidity . the optimum treatment of ks depends upon several factors , including location of lesions , disease progression , severity of symptoms and patient preference . we report the long - term response to the use of intralesional doxorubicin to successfully treat a large cutaneous lesion of ks on a patient refractory to traditional treatments .

cribriform - morular variant of papillary thyroid carcinoma ( cmv - ptc ) is a distinct ptc with a better prognosis . the affected patients have shown both germline and somatic mutations of adenomatous polyposis coli ( apc ) genes . unlike classic ptc , we report a case of cmv - ptc in a patient with apc , comparing with its documented cytomorphology and discuss its useful cytomorphological features in discriminating from other thyroid neoplasms . a 24-year - old female presented with altered bowel habits and bleeding per rectum was diagnosed with apc . at the same visit , she was diagnosed to have a multinodular goiter on imaging . hypercellular smears showed cells arranged in monolayer sheets , discohesive papillae , cribriform clusters , cell morules with scattered single cells in a clean background [ figure 1 ] . cribriform clusters showed slit - like and oval - to - round empty spaces surrounded by broad anastomosing bars of cells . the papillae had well - formed branching fibrovascular cores [ figure 2a ] , however , lacked sharp anatomical borders or nuclear palisading , unlike those seen in conventional ptc . the cells of papillae showed discohesion and spindling at the borders instead . the cellular composition varied with columnar cells at the edges of cell clusters , spindle cells attached to fibrovascular cores of papillae , and polygonal cells with small indistinct nucleoli in monolayer sheets . hypercellular smears showing monolayer sheets ( arrow ) with cribriform spaces ( star ) , discohesive clusters of cells ( arrow head ) and morules ( circle ) ( h&e stain , 100 ) ( a ) . papillae with well - formed branching fibro - vascular cores ( arrow ) and discohesive cells ( arrow head ) ( h&e stain , 100 ) . histology sections showing cribriform pattern ( h&e stain , 200 ) these cytomorphological features were unusual for conventional ptc . they were suspicious ; however , were not the classic features of cmv - ptc documented in the literature . therefore , it was placed in bethesda thyroid cytology diagnostic category 5 , suspecting a ptc variant . the thyroid contained multiple , circumscribed whitish nodules , distributed in both lobes and isthmus . immunocytochemical staining with beta - catenin and biotin as well have shown a value in cytological diagnosis . a series of 18 cases describe varying cellular arrangements with papillary pattern , which had been the predominant pattern in three - fourths of described cases . in contrast , papillae were rare in this case and those present showed cell discohesion with spindling at the edges instead of palisading . tall cells and spindle cells described as individual cells in the case series were present at the edges of flat monolayer sheets and papillary structures respectively in this case . the peculiar form of nuclear clearing , foamy / hemosiderin - laden histiocytes and background hyaline material additionally described in the case series were absent in this case . lack of colloid has been a constant feature both in the case series and this case . fascicular and solid patterns are described as additional architectural patterns in another series of five cmv - ptc cases . even though some degree of nuclear clearing and occasional nuclear inclusions were present , classical ptc nuclear features were absent in this case and the nuclei in general appeared to be of a higher grade than those seen in conventional ptc . the most salient features described in a series of another eight cases was the hypercellularity and papillary architectures in which the papillae have shown three - dimensional branching and prominent fibrovascular cores covered by single layers of cells with classical ptc nuclear features , unlike the papillae of this case . five other cmv - ptc cases additionally describe classical ptc nuclear features and cohesive papillary structures . additionally , they describe cells with abundant cytoplasm and distinct cell borders , which was additionally appreciated in some columnar and polygonal cells in this case . therefore , the cytomorphology of the present case is somewhat dissimilar to the features already described and those include papillae with cell discohesion and spindling at the periphery , presence of columnar cells only at the edges of flat monolayer sheets , absence of classic ptc nuclear features with the nuclei appearing to be of a higher grade than in ptc and discernible mitotic activity . varied cytomorphological appearance of cmv - ptc may raise the possibility of a range of differential diagnosis of ptc variants and other thyroid neoplasms . the tall cell variant of ptc ( tv - ptc ) may resemble cmv - ptc when abundant columnar cells are seen on smears . however , the varying cytological features and smaller number of tall cells in proportion in cmv - ptc will differentiate it from tv - ptc . tumor necrosis that may be present in tv - ptc is not described in cmv - ptc . the presence of architectural atypia and squamous morules raise the possibility of a diffuse sclerosing variant of ptc . however , the absence of significant nuclear pleomorphism , psammoma bodies , and sclerosing stromal fragments will be helpful to differentiate cmv - ptc from this variant . . however , nuclear stratification resembling metastatic endometrial / colonic carcinoma and the absence of classical ptc nuclear features will be helpful in differentiating it . however , the constellation of cytomorphological features of cmv - ptc in the absence of characteristic dispersed / powdery chromatin pattern of mc will make this diagnosis unlikely . sheets of cells with eosinophilic granular cytoplasm , distinct cell borders , nuclear clearing , grooves , and inclusions are common to both cmv - ptc and hurthle cell tumors hence , making their differentiation difficult . diagnosing cmv - ptc on smears would be challenging especially in view of its varied cytomorphological appearance . however , the full cytomorphological spectrum of cmv - ptc , when appreciated , may be characteristic enough to allow its accurate diagnosis . awareness of the varied cytomorphology of cmv - ptc avoids misdiagnosis , especially when it occurs sporadically , unassociated with fap . diagnosed apc patients , especially those with concurrent thyroid enlargement require exclusion of cmv - ptc , which has a recognizable cytomorphology and a favorable outcome .

cribriform - morular variant of papillary thyroid carcinoma ( cmv - ptc ) , which has a better prognosis , is seen mostly in the setting of familial adenomatous polyposis ( fap ) . the cytomorphology of cmv - ptc is diverse ; hence , it could be mistaken for other thyroid neoplasms with bad prognostic outcome . this case is of a 24-year - old female diagnosed with polyposis coli found to have thyroid nodules at screening ultrasonography . aspirated thyroid smears were hypercellular with epithelial cells arranged in monolayer sheets , papillae with discohesion , and spindling of cells at the edges , cribriform clusters , and cell morules . individual cell morphology ranged from polygonal , tall columnar to spindle cells . nuclei were round - to - oval with coarse chromatin , indistinct nucleoli , and mitotic figures . nuclear inclusions and grooves were rare and colloid was sparse . cytomorphology was suspicious , however , was not classical of cmv - ptc documented so far . subsequent histology confirmed a cmv - ptc .

taking advantage of the widespread symbiotic interactions pre - existing between yeast and drosophila , we have recently developed an oral delivery method to induce rna interference ( rnai ) in a pest insect by knocking down essential genes expressed in its digestive tract ( fig . 1 ) . by feeding d. suzukii with saccharomyces cerevisae transformed with a plasmid vector expressing double - stranded rna ( dsrna ) targeting y - tubulin23c ( y - tub23c ) , which is known to be lethal when mutated in the closely related d. melanogaster , we observed a significant decrease of y - tub23c mrna level in larvae and adult midgut of d. suzukii . more importantly , we observed that the reduced expression of y - tub23c mrna correlated with a significant reduction in both larval survivorship and adult reproductive fitness in a species - specific manner . our results are exciting because it showed that oral delivery of dsrna expressed in yeast can induce sufficient rnai knock down of a target gene to reduce fitness of an insect pest . the fact that the target insect for our study , d. suzukii , is a species without systemic rnai mechanism suggests that our approach may even be more effective in species with systemic rnai , in which the silencing signal can be more efficiently disseminated beyond the intial target cells , i.e. cells in the digestive tract . in addition , it remains to be tested in future experiments whether the delivery of dsrna by microbes , rather than naked dsrnas , could enhance the propagation of the rnai silencing signal . figure 1.schematic summarizing the protocol for production and oral delivery of genetically modified yeast expressing dsrna to insect targets . inverted repeats of target sequence are cloned into expression vector p406tef1 and transformed into s. cerevisae . previously expanded yeast culture is then pelleted and could be use for further applications . for more details , schematic summarizing the protocol for production and oral delivery of genetically modified yeast expressing dsrna to insect targets . inverted repeats of target sequence are cloned into expression vector p406tef1 and transformed into s. cerevisae . previously expanded yeast culture is then pelleted and could be use for further applications . for more details , 2 . since the first report of gene silencing using antisense single - stranded rna ( ssrna ) in plants at the end of the 1980s and a few years later in c. elegans , rnai efficiency have been notably improved with the discovery made by fire and mello highlighting the role of dsrna in this phenomenon . the use of dsrna molecules as a tool mediating sequence specific suppression of gene of interest ( goi ) was then extensively developed and utilized in many other organisms . despite the fact that rnai pathways are well conserved among eukaryotes , knockdown efficiency often varies depending on target species , target genes , and delivery methods . one of the major issue limiting the success of rnai strategies remains to be our incomplete understanding of mechanisms leading to the transport and amplification of dsrna molecules from one cell to another . the improvement of delivery methods also constitutes a critical step to effectively mediate knockdown phenotype . in a large number of insect taxa , oral administration has been reported to show similar efficiency on target gene expression when compared to injection methods . the obvious advantages of oral delivery include reduced stress for organisms and ease of use for small insects . nonetheless oral delivery of dsrna is still restricted to a few number of administration mode and to date , most rnai experiments using oral delivery are based on feeding dsrna either synthesized in vitro or produced in bacteria . among emerging applications , our use of genetically modified yeast as biopesticide presents a novel approach to extend the toolbox of integrated pest management ( ipm ) . studies on symbiotic interactions have indicated that yeast are not only restricted to drosophila but broadly spread across different insect taxa . in the mosquito aedes aegypti , recent finding has shown that live yeast cells are efficiently ingested and hydrolyzed by larvae . with the recent advances in sequencing technology , the characterization of insect gut microbiota will lead to the identification of novel symbiotic microorganisms amenable to be genetically modified and used as dsrna delivering vector . in the context of pest management , the finding of new species - specific interactions between insect and microbe will considerably increase the specificity of the treatment against targeted insect . beyond pest control strategies , the expansion of this technique constitutes a promising strategy to address the limits of rnai treatment , specifically in organisms where other delivery methods such as injection and classical oral dsrna administration remain unsuccessful or too expensive . recent advances in genetic and molecular biology offer a broad range of powerful technologies to manipulate expression and function of specific genes . with the development of genome engineering methods like znfs , talens and more recently crispr / cas9 system , our ability to generate genomic changes is bringing about a revolution in scientific discoveries . in model organisms such as drosophila , uas / gal4 system and this tool is particularly efficient to drive tissue specific and ectopic gene or dsrna expression , using promoter restricted to certain cell populations or developmental stage . although the development of these tools constitutes incontestable advances in terms of specificity and efficiency , there is still some exception where the use of exogenously delivered dsrna constitutes valuable alternative . indeed , genome engineering relies on the establishment of transgenic lines by injection of genetic constructs into embryonic germline cells , which could remain challenging in non - model insect systems . in addition , functional studies of genes playing distinct roles during development and adult life could be challenging since the loss of function of these goi generally leads to lethal phenotype . as shown in studies addressing the characterization of hormonal pathways for example , the same set of genes could be involved in both developmental processes and regulation of physiological state in an age - dependent manner . in such scenario , the temperature dependent uas / gal80 or other inducible systems can be used in model species . alternatively , the use of transient suppression of gene expression using rnai should also be considered . in fact , in experiments that require temperature manipulation in the experimental design , orally administrated or injected dsrna represent a helpful substitute to the gal80 temperature - dependent system . as high - throughput sequencing for genome and transcriptome acquisition is becoming more and more accessible , the opportunities to explore beyond the sphere of model organisms are now unlimited . as a consequence , the number of genes with unknown function continues to rise inexorably . in this context , the improvement of dsrna delivery has great potential in helping researchers tackle the genome to phenome challenge . we propose that microbial delivery of dsrna for gene silencing may be less time - consuming and labor - intensive than genome engineering and could be potentially applied to a broad range of organisms for reverse genetics study as well as integrated pest management .

abstractrna interference ( rnai ) by oral delivery of dsrna in insects has great potential as a tool for integrated pest management ( ipm ) , especially with respect to addressing the need to reduce off - target effect and slow down resistance development to chemical insecticides . employing the natural association existing between insect and yeast , we developed a novel method to enable the knock down of vital genes in the pest insect drosophila suzukii through oral delivery of species - specific dsrna using genetically modified saccharomyces cerevisae . d. suzukii that were fed with our yeast biopesticide showed a significant decrease in fitness . in this perspective article , we postulate that this approach could be adapted to a large number of species , given the great diversity of symbiotic interactions involving microorganisms and host species . furthermore , we speculate that beyond its application as biopesticide , dsrna delivery by genetically modified microbes can also serve to facilitate reverse genetic applications , specifically in non - model organisms .

a total of 1,217 dead birds were shipped at 4c to the tropical medicine institute " pedro kouri " and identified by ornithology experts . brain , heart , and kidneys were removed and tested for wnv by using reverse transcription polymerase chain reaction ( rt - pcr ) ( 12 ) . briefly , rna was extracted by using the qiamp viral rna kit ( qiagen , inc . , valencia , ca , usa ) . primers wn212 ( 5-ttgtgttggctctcttggcgttctt-3 ) and wn619c ( 5-cagccgacagcactggacattcata-3 ) were used to detect viral rna . a second rt - pcr with primers wn9483 ( 5-cacctacgccctaaacactttcacc-3 ) and wn9794 ( 5-ggaacctgctgccaatcataccatc-3 ) was performed on the same rna preparation . serum specimens from horses in havana and havana province were tested for antibodies to wnv by using a competitive enzyme - linked immunosorbent assay ( elisa ) with monoclonal antibodies 3.1112 g and 6b6c-1 as described by blitvich et al . we tested 210 serum specimens from horses collected as part of an infectious anemia study . the immunoglobulin m ( igm ) test was not performed because horses were never suspected of having wnv and did not have any history of suspected viral encephalitis or other illness or symptoms . an inhibition value > 30% was used as the diagnostic criterion to identify flavivirus antibody ( table 1 ) . * wnv , west nile virus ; elisa , enzyme - linked immunosorbent assay ; prnt , plaque reduction neutralization test ; slev , saint louis encephalitis virus . the cuban health ministry and medical services division conducted surveillance for encephalitis of unknown origin in patients > 30 years of age . serum and cerebrospinal fluid specimens were shipped at 4c to the tropical medicine institute " pedro kouri . " human sera were screened for wnv igm and igg by using commercial igm and igg elisa kits ( focus technologies , cypress , ca , usa ) according to manufacturer 's instructions . hemagglutination - inhibition ( hi ) tests were also undertaken with wnv and saint louis encephalitis virus ( slev ) antigen ( 14 ) . reactive serum samples were further tested by a plaque reduction neutralization test ( prnt ) with wnv ( ny99 , ontario , canada , 2001 isolate ) , slev ( parton strain , american type culture collection catalog no . vr-1265 ) , and dengue virus ( dengue 2 , ng - c strain ) . prnt was performed to confirm wnv - specific antibody and was carried out as described previously ( 15 ) by using a neutral red double - overlay procedure . horses or human patients were considered seropositive for a particular flavivirus if the 90% prnt titer for that virus was > 4-fold greater than the neutralization titers determined for other viruses used in the assay . endpoint titrations were defined as the highest dilution of serum that reduced plaque formation by > 90% . most ( 58% ) of the 1,217 birds tested were resident species of cuba , primarily chestnut manakins ( lonchura malaccas ) , blue jays ( cyanocitta cristata ) , herring gulls ( larus argentatus ) , yellow - faced grassquits / olive finches ( tiaris olivacea ) , and northern parulas ( parula americana ) . nineteen ( 9.0% ) of the 210 horses had serum specimens with antibodies to flaviviruses ( table 1 ) . four and 8 animals had wnv- and slev - specific antibodies , respectively , in the prnt . two horses seropositive for wnv came from havana city , and 2 others came from havana province . seven serum samples had antibodies to undetermined flaviviruses on the basis of results of neutralization assays , and further virus characterization was not performed . none of the horses , including those that were positive for flavivirus antibodies , showed any signs of illness at the time of serum collection . both acute - phase and convalescent - phase serum specimens from these patients were positive for flavivirus antibody by igm and igg elisas ( table 2 ) . convalescent - phase serum samples were tested for wnv - specific antibody by prnt , and the neutralization titers were 320 and 160 , respectively . neutralizing antibodies against slev or dengue virus these persons are the first to have confirmed cases of wnv - associated illness in cuba . both patients had histories of febrile illness , muscle weakness , and encephalitis , and both were hospitalized . these persons had jobs that required them to spend large amounts of time outdoors , and they lived in communities in santi spiritus and villa clara in central cuba . , table 2 ) , who also resided in santi spiritus , had a low wnv titer by hi assay but had neutralizing antibodies to wnv , which suggests a past wnv infection . this patient was identified during surveillance in 2004 but may have been exposed to wnv in 2003 . * wnv , west nile virus ; elisa , enzyme - linked immunosorbent assay ; prnt , plaque reduction neutralization test ; ig , immunoglobulin ; hi , hemagglutination inhibition ; slev , saint louis encephalitis virus ; denv , dengue virus ; nd , not done . acute - phase / convalescent - phase serum samples . serum specimens from the 10 remaining patients were negative for wnv igm but were positive for flavivirus igg by elisa ; most of these were also positive by hi assay ( table 2 ) . one person appeared to have been exposed to dengue virus , and 4 had antibodies to unidentified flaviviruses . seroconversions were not demonstrated in any of these persons , so we can not say whether their illnesses were associated with slev or dengue virus infections . we report the first evidence of antibodies to wnv in horses and humans in cuba . the fact that human and horse infections have been detected strongly suggests that a local amplification cycle has been established in cuba . the mode of entry of the virus into cuba is unknown . in north america , avian death from wnv infection has been well documented ( 35 ) . however , none of the dead birds collected during this study showed evidence of viral infection . although 1,217 animals were tested , a more intensive dead bird surveillance program may be needed to identify animals that die from wnv infection . resident bird species in cuba may be less susceptible to wnv infection , and death rates among birds in the caribbean may be lower than those observed in canada and the united states . this study also provides evidence that suggests wnv and slev may co - circulate in cuba . further studies are required to confirm these observations and to characterize the transmission cycles involved . finally , expansion of existing mosquito control programs in cuba , which currently focus on aedes aegypti and dengue prevention , may be required to respond to this new public health threat .

a surveillance system to detect west nile virus ( wnv ) was established in cuba in 2002 . wnv infection was confirmed by serologic assays in 4 asymptomatic horses and 3 humans with encephalitis in 2003 and 2004 . these results are the first reported evidence of wnv activity in cuba .

cavernous hemangioma is a benign vascular malformation and belongs to a wide and continuous overlapping spectrum of hamartomas . most cavernous haemangiomas occur in the vertebral body and may extend into the epidural space . purely extradural cavernous hemangiomas without any vertebral body involvement is extremely rare and accounts for only 4% of all extradural spinal tumors and 12% of haemangiomas occurring extradurally . we herein present a rare case of extradural dumbbell lumbar ( l3 ) cavernous hemangioma with paraspinal extension . a 52-year - old female presented with insidious onset progressive low backache with pain radiating to whole of left lower limb associated with paraesthesias for two months . left lower limb power was 4/5 in hip flexion , extension , abduction and adduction , 4/5 in knee flexion and extension , subtle weakness in ankle flexion and extension and great toe extension with hypotonia . the reflexes of left lower limb were sluggish whereas on right side they were brisk ( normal ) . sensory examination revealed impairment of all the modalities of sensations ( pin prick , touch , temperature , vibration- impaired upto anterior superior iliac spine ) from l2 to s4 dermatomes on left side . magnetic resonance imaging of lumbar spine revealed an irregularly shaped , well defined extradural lesion at l3 vertebral level indenting the body , displacing the thecal sac posterolaterally and extending into left paraspinal region through l3- 4 neural foramen . lesion was isointense on t1w , hyperintense on t2w images with strong homogenous enhancement on gadolinium contrast study [ figure 1 ] . provisional preoperative diagnosis of schwannoma was considered . though the clinical findings and radiology were not concordant , the patient was suggested surgical intervention for the presence of enhancing mass lesion noted on the imaging with guarded prognosis . shows irregularly shaped well defined extradural lesion ( arrows ) , hypointense on t1w ( a ) , hyperintense on t2w ( b ) images with homogenous contrast enhancement ( c , d , e ) and paraspinal transforaminal extension ( d , e ) the patient underwent left hemilaminectomy from l2 to l4 . there was an extradural , brownish red , highly vascular mass located anterolateral to thecal sac at l3 vertebral body with well defined capsule around it . left l3 nerve root was pushed superiorly by the tumor and it was not arising from any neural tissue . it was dissected clear from the l3 nerve and the dura keeping the dissection over the coagulated capsule . the spinal component of the lesion was excised in toto until the neural foramen , where it was coagulated and was cut sharply leaving behind the extra - foraminal portion . microscopic examination revealed numerous dilated vascular channels of variable sizes lined by a single layer of flattened epithelial cells and filled with blood elements . interspersed thick hyalinised blood vessels and mature adipose tissues were noted [ figure 2 ] . radiotherapy was administered to the residual paraspinal portion of tumor [ figure 3 ] . for radiotherapy , the patient was immobilised in a vacuum locking device and ct simulation was done in the treatment position . margin of 1 cm was added to the post contrast t1w mri to obtain the clinical target volume ; planning target volume was obtained by adding a margin of 0.5 cm to the clinical target volume . three dimensional conformal radiotherapy was planned on eclipse planning system ( varian medical systems , palo alto , ca ) on linear accelerator ( clinac ix- 3665 ) using 6 mv x rays . the dose prescription was 40 gy , 2 gy per fraction , 20 fractions given five days a week over five weeks . ( a , b ) the proliferating and anatomizing capillary channels lined by endothelial cells ( h and e , 100 ) shows postoperative changes ( arrow ) in spinal canal and residual tumor in paraspinal region cavernous hemangioma is a benign vascular malformation , also known as cavernous malformation , cavernous angioma or cavernoma . the cavernous hemangiomas occur throughout the neuroaxis including both intracranial and spinal compartments . according to location , its incidence in supratentorial , infratentorial and spinal compartments is 80% , 15% and 5% respectively . purely extradural spinal cavernous hemangiomas are rare and the extension through intervertebral foramen into extraspinal region ( dumbbell ) is still rarer . in that case , it can be confused with commonly diagnosed nerve sheath tumors . the onset of symptoms in these spinal cavernomas may be acute , progressive or remittent , depending on the biological behavior of the tumor . lumbar extradural hemangiomas behave differently , not only from intramedullary cavernous hemangiomas but also from extradural cavernomas of other spinal locations . purely extradural hemangiomas should be included in the differential diagnosis of lumbar extradural soft - tissue lesions . in contrast to intracerebral cavernous hemangiomas , the patterns of density on ct scans and signal intensity on mr images are more homogenous in extradural hemangiomas . another point of differentiation is the absence of low signal rim ( hemosiderin ) which is usually seen in intraaxial spinal cord cavernomas . as seen in present case , extradural cavernous hemangiomas are usually isointense on t1w and hyperintense on t2w images and show homogenous contrast enhancement because of the presence of sinusoidal channels . the lesion should be differentiated from other epidural neoplastic or inflammatory conditions , such as meningioma , neurofibroma , lymphoma , hemorrhagic vascular mass , granuloma and angiolipoma . complete and in toto excision of the lesion should be attempted for clinical improvement ; however , in case of subtotal excision , adjuvant radiotherapy is advised . radiosurgery as primary or adjuvant therapy is increasingly becoming an option as advances in radiosurgical equipment are enabling safe and accurate targeting of lesions . though purely extradural cavernomas are rare in occurrence , they should be considered as possible differential diagnosis of dumbbell lesions of spine in view of operative nuances ( especially massive haemorrhage ) and management thereof .

a 52-year - old female presented with slowly progressive left lower limb polyradiculopathy . mri of the lumbar region revealed an extradural dumbbell mass at l3 vertebral level , isointense on t1w and hyperintense on t2w images with homogenous contrast enhancement and extending into paraspinal region through left l3/4 foramen . l2 to l 4 left hemilaminectomy and excision of intraspinal part of tumor was performed . histopathological examination revealed presence of cavernous hemangioma . this case is reported because of its rarity , unusual dumbbell shape of lesion and difficulty in making a preoperative diagnosis without a coexisting bone lesion .

over - the - counter cold medicines , which contain amantadine , are widely used in the people s republic of china . clinicians are familiar with the psychosis caused by long - term treatment with amantadine , especially in elderly patients ; however , early - onset psychotic complications among healthy young individuals have rarely been reported . this article reports the case of a 28-year - old patient who presented with hallucination delusion syndrome soon after treatment with cold medicine containing amantadine hydrochloride and acetaminophen . clinicians should be sensitive to the acute psychotic complications induced by an interaction between amantadine and acetaminophen . over - the - counter cold medicine , which contains amantadine , is widely used in the people s republic of china . typically , it takes several months of amantadine administration to bring about these side effects.1 in this article , we report on the case of a 28-year - old patient suffering from a cold who presented with hallucination delusion syndrome immediately after the use of a cold medicine containing amantadine hydrochloride and acetaminophen . a 28-year - old man was admitted to the first affiliated hospital of zhejiang university school of medicine because of hallucinations and persecutory delusions , which lasted for ~48 hours . when he was alone at home , he had an auditory hallucination that his parents described of inviting a taoist , and he heard that his birthday horoscope did not match with that prepared by his parents . the auditory hallucinations lasted for almost an entire day and severely affected the patient s sleep . prior to admission , he had been in excellent health and did not have a history of medical problems , psychiatric disorders , or substance abuse . he was born in zhejiang province of the people s republic of china and had not traveled elsewhere . five days prior to admission , he reported symptoms of a cold , including a runny nose , and had therefore started taking an over - the - counter cold medicine ( brand name : kuaike ) , which contained 250 mg of acetaminophen and 100 mg of amantadine hydrochloride . three days later , he began to experience hallucinations and delusions . during the mental status examination administered upon admission , however , he frequently looked down and did not maintain eye contact with the examiner . his speech was a bit slow , but with normal tone , rhythm , and prosody . although the patient acknowledged his own abnormal mental state , his insight was still partially impaired . laboratory studies revealed complete blood count , electrolytes , glucose , urea , creatinine , hepatic function , and thyroid hormone levels within normal limits , and the rapid plasma reagin test , serum human immunodeficiency virus ( hiv ) antibody test , and urinalysis for narcotic drugs were negative . the patient was immediately treated with haloperidol ( 5 mg daily ) and paliperidone extended release ( 3 mg daily ) , while kuaike administration was ceased . haloperidol was used for 3 days , and the use of paliperidone extended release was maintained for 2 weeks to prevent relapse . six months later , we conducted a telephonic follow - up , wherein the patient reported of no subsequent psychotic experiences . written informed consent was obtained from the patient for the publication of this case report . the report was approved by the first affiliated hospital of zhejiang university school of medicine ethics committee . written informed consent was obtained from the patient for the publication of this case report . the report was approved by the first affiliated hospital of zhejiang university school of medicine ethics committee . existing literature reports about several drugs that could induce acute psychosis , such as psychostimulants,2,3 antibiotics,4 antivirals,5 and antiparkinsonism.6 amantadine is indicated for the treatment of influenza a , parkinsonism , and drug - induced extrapyramidal reactions . increasing evidence shows that amantadine enhances dopamine release indirectly via antagonism of the n - methyl - d - aspartate receptor , and this mechanism may be responsible for this rarely exhibited psychotic side effect.7 n - methyl - d - aspartate antagonists , such as ketamine , can induce the positive , negative , and cognitive symptoms of schizophrenia.8 there are numerous reports of amantadine being prescribed for long - term antiparkinsonian effect.9,10 however , to our knowledge , there were only three previous reports of rapid psychiatric complications among otherwise healthy and young individuals . the first report described an acute psychosis secondary to an amantadine overdose,11 the second noted the emergence of psychosis following 100 mg of amantadine twice daily in combination with venlafaxine and quetiapine,12 and the third study presented two cases of psychosis among 295 subjects in an antiviral trial of amantadine.13 the current case demonstrates the potential adverse effects of amantadine on the central nervous system among young healthy adults at the standard dose . although the incidence of this induced psychosis is low , it may increase with the daily administration of amantadine , and clinicians should be aware of the rapid onset of these psychotic complications . recently , the use of amantadine in the treatment of influenza a has been discouraged.14 because of its limited effectiveness , amantadine is only recommended for use during a serious epidemic or pandemic alongside other public health measures.15 although we believe that amantadine was the primary cause of this patient s psychosis , we can not exclude the effects acetaminophen might have had in this adverse reaction . there have been only two reported cases of acetaminophen use associated with psychosis : acetaminophen in combination with codeine and acetaminophen overdose.16,17 acetaminophen has been reported to have an inhibitory effect on prostaglandin synthase in the brain,18 and prostaglandin itself has been linked to the etiology of schizophrenia.19 over - the - counter cold medicines containing amantadine are widely used in the people s republic of china . clinicians should be aware of the severe side effects of these medicines on the central nervous system .

backgroundover - the - counter cold medicines , which contain amantadine , are widely used in the people s republic of china . clinicians are familiar with the psychosis caused by long - term treatment with amantadine , especially in elderly patients ; however , early - onset psychotic complications among healthy young individuals have rarely been reported.case presentationthis article reports the case of a 28-year - old patient who presented with hallucination delusion syndrome soon after treatment with cold medicine containing amantadine hydrochloride and acetaminophen . the symptoms resolved completely after a 2-week course of paliperidone treatment.conclusionclinicians should be sensitive to the acute psychotic complications induced by an interaction between amantadine and acetaminophen .

laparoscopic sleeve gastrectomy ( lsg ) is currently one of the most commonly performed bariatric surgeries in the world . known perioperative complications include haemorrhage , leak , small bowel obstruction and infections ( mostly wound and intra - abdominal abscess ) . intra - abdominal abscess presents in < 1% of all procedures , and , to the best of our knowledge , only six cases of splenic abscess as a complication of lsg exist in the literature [ 26 ] . a 45-year - old woman with a past medical history significant for essential hypertension , asthma and morbid obesity status post lsg 20 days before admission , presented with abdominal pain of 10 days duration . the pain was localized to the left upper quadrant and was associated with fever , chills , nausea and infrequent vomiting . at the time of the lsg , her post - operative course was uneventful and she was discharged home 3 days after admission . however , she had not attempted any solid food due to nausea . on admission , physical exam was significant for mild pain on palpation of the left upper abdominal quadrant . a computed tomography ( ct ) of the abdomen was obtained and showed a well - circumscribed 7.1 by 5.4 cm air - fluid collection in the medial aspect of the spleen . of note , an upper gastrointestinal series with gastrografin showed no evidence of leak from her gastrectomy staple line . the patient was started on empiric piperacillin / tazobactam and a ct - guided drainage of the abscess was performed . the patient was treated with meropenem and linezolid for 4 days , and then switched to intravenous ceftriaxone once the microbiology results became available . she was discharged home to complete 2 weeks of intravenous antibiotics . however , after 3 weeks the patient returned to the hospital with new left upper abdominal pain that referred to the left shoulder , poor oral intake , fever and shortness of breath . a repeat ct of the abdomen showed an air - fluid collection in the medial spleen comparable in size to the one present at post drainage . a ct - guided drainage of the splenic abscess was performed and the patient was discharged home to complete 2 weeks of intravenous ceftriaxone and oral metronidazol . splenic abscess is a rare occurrence , with the vast majority of the available literature consisting of case reports and series from tertiary care centres . splenic abscess as a complication of lsg appears to be an extremely rare entity with only six cases in the literature [ 26 ] . these patients were ages 1946 , none had a reported immunosuppressive condition , presented in the late post - operative period , and only one had an intraoperative complication ( table 1 ) . previous authors have pointed out that splenic abscess in the bariatric population could have a different aetiology from the classically described in the general population . among the proposed factors are extension from a gastric staple - line leak , splenic injury during surgery and inadvertent splenic ischaemia [ 3 , 6 ] . regarding the latter , in a recently published series of 565 lsg , 0.53% presented with splenic abscess in post - operative days 914 . interestingly , the authors of this paper reviewed the video recordings of all cases and reported a rate of spleen infarcts of 7.79% . all splenic abscesses in this series had evidence of infarct during the original procedure , leading them to suggest that they are both related . a similar study with closer follow - up suggested this as well . in our case , there was no evidence of intraoperative injury to the spleen , staple - line leak or splenic ischaemia . the causative agent was s. anginosus , usually found as a commensal of the oral cavity and gastrointestinal tract , but capable of suppurative infections that are often associated with antecedent disruption of the gastrointestinal mucosa . in the present patient , without any obvious perforation or anastomotic leak , haematogenous spread caused by transient bacteraemia during the surgical procedure is certainly a possibility . she responded well to the combination of intravenous antibiotics and percutaneous drainage , and there was no need for splenectomy . table 1characteristics of previous case reports of splenic abscess as a complication of lsg.case ( reference)age / seximmunosuppressionimmediate complicationspost - operative day of presentationtreatmentevidence of leakagecultured organismrojas et al . 46/fnohaemoperitoneum , splenic hilum and hepatic injury14iv antibiotics , percutaneous drainageyess . no75iv antibiotics , percutaneous and laparoscopic drainagenostaphylococcusspp.,enterobacter cloacae , streptococcus mitis and oralisavulov et al . 44/mnono70iv antibiotics , percutaneous drainage , splenectomynoklebsiella pneumoniae , streptococcus pneumoniae , acinetobacterspp.current study , 201645/fnono20iv antibiotics , percutaneous drainagenos . anginosus characteristics of previous case reports of splenic abscess as a complication of lsg . in conclusion , splenic abscess is an uncommon complication of lsg , albeit one that should be entertained in the patient with abdominal pain and fever given its high mortality . a ct of the abdomen with contrast is the preferred diagnostic tool ; patients should be treated with a combination of intravenous antibiotics and either percutaneous drainage or splenectomy . further studies with a larger sample of lsg patients should be conducted in order to elucidate the role of splenic ischaemia in abscess formation .

abstractsplenic abscess as a complication of laparoscopic sleeve gastrectomy ( lsg ) is rare . there have only been six cases in the literature . in most of these cases , the classic predisposing factors for developing splenic abscess were absent , leading to the hypothesis that transient bacteraemia caused by mucosal disruption during the surgical procedure and splenic ischaemia may play a role . these patients usually present in the late post - operative period with abdominal pain , fever and leucocytosis . the preferred treatment is intravenous antibiotics and percutaneous drainage or splenectomy . we report a case of splenic abscess caused by streptococcus anginosus that occurred 20 days after lsg in a 45-year - old woman without immunosuppressive conditions . the patient was successfully treated with antibiotic therapy and percutaneous drainage .

osteoporosis - related fractures are a major public health problem mainly in postmenopausal women and the elderly . osteoporosis affects an estimated of 75 million people in europe , united states of america , and japan . there are several treatment options available including calcium , vitamin d , parathyroid hormone , strontium , and bisphosphonates . alendronate ( fosamax , merck & company , inc . ) is one of the first bisphosphonates to be licensed and used . recently , however , there is an emerging concern regarding long bone stress fractures secondary to long - term alendronate intake . we present a case of bilateral femoral shaft insufficiency fractures secondary to long - term alendronate therapy . a 74-year - old lady presented to orthopaedic clinic with a four - month history of bilateral thigh pain . she had history of breast cancer treated with lumpectomy 10 years ago and has a history of well - controlled asthma , for which she did not require corticosteroid treatment . radiographs revealed lateral cortical thickening of the mid - diaphysis of both femurs ( figure 1 ) . the patient underwent a bone scan to rule out the possibility of metastases due to her previous history . four days after consultation , she tripped and sustained a transverse fracture of the left femur and underwent uneventful femoral intramedullary nailing ( figures 3(a ) and 3(b ) ) . bone mineral density scan was organized , and she was started on teriparatide treatment . because there was no progressive right thigh pain , no further surgical management was offered beyond close followup . at four months postoperatively , the left femur fracture showed good radiological union ( figure 3(c ) ) . there was still persistent pain in the right femur and a definite linear lucency in the lateral femoral cortex on plain radiographs . she underwent prophylactic intramedullary nailing of the right femur and had eventual complete relief of her symptoms . the lifelong risk of having a fracture related to osteoporosis is one in two for women and one in four for men . bone formation coupled to resorption is also decreased resulting in an overall reduction of bone remodelling . bisphosphonates also combine with calcium and become incorporated in the crystal structure of bone and retained within the skeleton for long periods of time . therefore , they have the potential to exert efforts long after the treatment has been discontinued . alendronate is the first bisphosphonate to be approved for the treatment and prevention of osteoporosis . several previous studies have shown that alendronate reduces the risk of osteoporotic fractures and osseous resorption in high turnover bone disease . it has an excellent benefit to risk ratio for women with osteoporosis when used for 3 - 5 years . in addition to other well - known side effects of bisphosphonates , there is a recent concern regarding the association of cortical insufficiency fractures and low - energy femoral fractures with long - term alendronate use . several published case series and case reports suggest femoral shaft , and subtrochanteric femur fractures can be associated with long - term alendronate use [ 24 ] . have shown a significant proportion of patients , in their study of low - energy sub - trochanteric and diaphyseal femur fractures , were on long - term bisphosphonates . the characteristic features include prodromal pain in the thigh for several months prior to the fracture ( 76% of the reported cases ) , bilateral fractures either sequential or simultaneous , and fractures with trivial trauma . the radiological features of these fractures are lateral cortical thickening , cortical spiking or beaking over the medial cortex , and transverse or short oblique fractures . neviaser et al . reported in their study that 19 of the 25 patients on alendronate demonstrate a simple transverse fracture with a unicortical beak in an area of cortical hypertrophy . in contrast , this fracture pattern was seen in only one patient who was not being treated with alendronate , indicating that the fracture pattern is typical in alendronate users . alendronate acts as a strong inhibitor of osteoclastic bone resorption which reduces the overall bone turnover . this has a negative effect on bone healing and is likely one of the reasons why many of the insufficiency fractures have delayed healing . since alendronate inhibits osteoclastic remodeling , endochondral fracture repair is the preferred method of fracture healing . intramedullary reconstruction with full - length nails accomplishes this goal and protects the entire femur . sayed - noor and sjdn reported a case series of delayed union even after internal fixation of a femoral insufficiency fracture in a patient who was on long - term alendronate . capeci and tejwani and ha et al . reported union at an average of four and five months , respectively , after internal fixation [ 7 , 8 ] . in our case , the left femur fracture was treated with a reamed intramedullary nail with union at four months . because of the nonprogressive pain from the right femur stress fracture , close observation with protective weight - bearing was initially chosen but proved to be insufficient despite stopping alendronate . we support the view of capeci and tejwani and ha et al . to treat even the incomplete insufficiency fractures with internal fixation . as well , we feel clinicians should not be lured into conservative management by the radiographic features of focal cortical hypertrophy . dietary calcium and vitamin d status should be assessed , and adequate supplementation should be prescribed . although there is strong evidence supporting short - term alendronate therapy to reduce the risk of osteoporotic fractures , there is not enough evidence to suggest benefit in long - term use beyond five years . the continuation of alendronate therapy after five years should be tailored to individual patients after appropriate followup and the need for ongoing therapy reassessed annually . any patients with prodromal symptoms such as thigh pain should be investigated with routine bilateral radiographs of the femur looking for stress reaction , and if necessary , advanced imaging - like bone scan or magnetic resonance imaging . this is not the first case report on insufficiency diaphyseal fractures related to long - term alendronate therapy . however , this is a case report with characteristic features and bilateral involvement which highlights the importance of evaluating patients on long - term alendronate therapy and recommends early prophylactic internal fixation of these fractures . patients on more than 5 years of alendronate therapy should be reevaluated annually regarding continuation of treatment and need close observation .

osteoporosis - related fractures are a major public health problem and one in two women and one in four men are affected with osteoporosis - related fractures . alendronate ( fosamax ) is one of the first bisphosphonates used to treat osteoporosis effectively . recently , however , there is a concern regarding long bone insufficiency fractures related to long - term alendronate therapy . we report a case of bilateral femoral insufficiency fractures likely related to long - term alendronate therapy , the classic symptoms , signs , and treatment of these fractures .

water disturbance may occur in hemorrhagic and ischemic stroke patients because of the major role that the central nervous system plays in water homeostasis [ 13 ] . post - stroke hypernatremia is generally the consequence of central diabetes insipidus , but it can also take place if the patients do not have free water access , usually as the result of neurological sequels which prevents them from drinking water or even asking for it from their relatives and caretakers . hypodipsia secondary to lesions of the thirst center , not accompanied by other serious neurological damage , is a rare cause of post - stroke hypernatremia , but it may cause significant morbidity if not properly diagnosed and managed . a 56-year - old caucasian man was admitted to the cardiology ward of our hospital due to lethargy and muscle weakness , attributed to the presence of bradycardia . routine admission laboratory tests revealed high plasma sodium levels ( na : 157 meq / l ) , which motivated , on the following day , a request for nephrology evaluation . at nephrology consultation his past medical history revealed that 9 years previously he had had a hemorrhagic stroke and needed brain surgery to clamp a ruptured aneurysm of the anterior communicating artery and to drain a cerebral hemorrhage . a representative figure of patient s cranial computed tomography ( ct ) done at that occasion is presented in figure 1 . the stroke resulted in some impairment of the capacity of space location , moderate reduction of the recent and fixation memory and a certain aversion to water . new laboratory tests were ordered and confirmed hypernatremia : plasma sodium of 155 meq / l and plasma chloride of 116 meq / l . urinalysis : urine - specific gravity of 1026 , no blood or protein and a normal sediment . plasma potassium , creatinine and urea were , respectively , 4 meq / l , 1.07 mg / dl and 41 mg / dl . in the 24 h that followed nephrology consultation , the patient passed only 400 ml of urine . the diagnosis of possible hypernatremia secondary to post - stroke hypodipsia was then made and supervised water intake of 2 l a day was initiated . after this simple measure , there was an increase in diuresis and plasma sodium was reduced to 150 meq / l on the third day and to 144 meq / l on the fourth day after admission . two weeks after hospital discharge , he had gained 3 kg and referred marked improvement in lethargy and muscle weakness . the evolution of the patient s laboratory tests , including the ones collected 2 weeks after hospital discharge , are presented in table 1 . evolution of plasma sodium and other laboratory tests after patient s hospital admission cranial ct scan showing diffuse subarachnoid hemorrhage ( inferior white arrow ) , frontal left intraparenchymatous hematoma ( superior white arrow ) , intraventricular hemorrhage ( inferior black arrow ) and nodular slightly hyperdense image with peripheral calcifications on anterior communicating artery topography , suggestive of giant aneurysm ( superior black arrow ) . hypernatremia is relatively frequent in clinical practice , being common in the elderly and in critically ill patients . in patients with free access to water when plasma sodium ( the main determinant of plasma osmolality ) increases , two defense mechanisms are triggered : stimulation of the thirst center and secretion of antidiuretic hormone ( adh ) . this combination results in increased water intake and reduction in urinary water loss , leading , thus , to normalization of plasma osmolality . this mechanism is highly efficient , keeping plasma osmolality in a narrow range , despite the daily variation of water and sodium intake . in the reported case , the patient s mechanism of adh liberation and the urinary concentration were preserved : when faced with significant hypernatremia , the patient s 24-h urine volume was only 400 ml , and the urine had high specific gravity ( 1.026 ) ; normalization of plasma sodium concentration , urine dilution and weight gain occurred when supervised water intake was warranted . this case illustrates the fact that even when the mechanisms of adh liberation and urine concentration are intact , and if the thirst mechanism is damaged , the body is not capable of maintaining normonatremia [ 3 , 6 , 7 ] . post - stroke hypodipsia may be the result of damage to the hypothalamic thirst center , believed to be present in the lamina terminalis of the third ventricle in the presented case , there was extensive intraventricular hemorrhage but this may occur even in the absence of ct evidence of hypothalamic damage , possibly due to a cortical central nervous system lesion that interferes with cortical perception of thirst . the clinical symptoms that motivated the patient s hospital admission and that were at the first attributed to bradycardia were apparently caused by hypernatremia . in fact , this patient had been presenting muscle weakness and lethargy very frequently in his daily life and his wife reported that these symptoms had begun after the stroke . indeed , the review of his past laboratory test values revealed that in the course of medical evaluations done in the past , high values of plasma sodium were documented ( 170 meq / l in september 2007 and 151 meq / l in february 2009 ) but were misinterpreted as laboratory artifacts since the patient presented no physical sequels of the hemorrhagic stroke and , as hypernatremia was chronic , significant neurological symptoms were absent . sadly , a second measurement of plasma sodium was not ordered on neither of those two occasions . the patient s weight loss was secondary to true dehydration since it was quickly corrected after appropriate water intake . no medical reason was found for the patient s bradycardia , but when discharged from hospital , his heart rate was 72 b.p.m .

disorders in water metabolism may occur in stroke patients . when hypernatremia arises in this setting , it is usually secondary to the development of central diabetes insipidus or it is the result of neurologic lesions that prevent patients from having free access to water . much rarer are the cases of post - stroke hypernatremia caused by hypodipsia secondary to lesions of the thirst center . we report the case of a patient with severe hypernatremia , probably secondary to post - hemorrhagic stroke hypodipsia . the hypernatremia seen in this case was corrected by scheduling the patient s water intake .

melanoma is the malignant tumor of melanocytes which may present in a wide morphological spectrum including highly pigmented to amelanotic appearance . clinically there are four main subtypes of cutaneous melanoma : superficial spreading melanoma , lentiginous melanoma , nodular melanoma and acral lentiginous melanoma . the diagnosis of amelanotic variants of melanoma may especially be challenging both clinically and histologically . in addition to clinical variants of melanoma , in the literature various atypical histological variants of melanoma have been reported , such as fibroblastic , desmoplastic , chondroid , osteoid , and myxoid melanoma , which were classified according to stromal changes [ 13 ] . myxoid melanoma is an unusual variant of malignant melanoma , which is characterized by atypical spindle cells and dense mucin deposition in dermis . the prevalence of this melanoma variant is not well known and may develop on cutaneous or extracutaneous sites , including the sino - nasal passages . this tumor may be confused with other mucin - containing neoplasms , histologically benign or malignant , and clinically is usually reported in elderly people with a similar progress to other variants of melanoma . a 28-year - old male presented to our outpatient clinic with a history of an asymptomatic pink nodule which had been growing slowly for last 6 months . dermatological examination revealed a 2.5 x 2 cm diameter pink , mildly infiltrated tumoral lesion with two pigmented papular lesions on left arm ( figure 1 ) . dermoscopic examination revealed pink - white cristalline structures and blue - grayish ovoid globules ( figure 2 ) . the lesion was totally excised with 3 mm margins with the initial diagnosis of basosquamous carcinoma , amelanotic melanoma and basal cell carcinoma . histopathological examination was consistent with myxoid melanoma with breslow thickness 11.6 mm , clark level v ( figure 3a , b ) . there was no vascular , lymphatic or perineural invasion histologically , and mitoses 2/1 per mm . strong positivity was detected with s100 and hmb45 staining , and widespread positive staining was detected with pas - alcian blue for mucin deposition ( figure 4a , b ) . laboratory tests , including complete blood count , routine biochemistry , lactate dehydrogenase and beta-2 microglobulin and imaging test for metastasis , including pet - ct and sentinel lymph node biopsy , were all clear . the patient is currently well and clinically free of recurrence 18 months after the diagnosis . the presence of myxoid stroma in malignant melanoma was first published by bhuta et al in 1986 in four metastatic malignant melanomas . clinically these tumors were reported to be amelanotic , but in some cases melanogenesis was also shown with fontana masson preparations . histologically , this rare variant of melanoma is characterized by large malignant melanocytes and a basophilic mucinous matrix . in all cases , the myxoid stroma is comprised of mesenchymal acidic mucopolysaccharides , as opposed to neutral epithelial mucins . mucinous material is usually located around the tumor cells , as in our case , but not within the tumor cells as in cytoplasmic localization , confirming that the myxoid matrix is produced as a response to the stromal cells in the tumor rather than being a product of the tumor cells . myxoid changes are more often reported in metastatic tumors than in primary malignant tumors , but in our patient due to the completely intradermal location of tumor cells with no junctional component , ith a nodular architecture , features of malignancy , no ulceration , the absence of peripheral nerves , and an absence of preexisting melanocytic nevus , he was diagnosed as primary dermal melanoma . additionally , based on the histopathologically myxoid stromal changes , he was diagnosed as primary myxoid melanoma . also no other metastatic or primary malignant lesion typically , s100 staining is strongly positive , but immunostaining with hmb-45 is less uniform and both positive and negative results were reported in the literature . in our patient both s100 and hmb45 staining were strongly positive . the differential diagnosis of myxoid melanoma is broad , including several other benign and malignant myxoid neoplasms of soft tissue as well as epithelial cancers such as myxoid liposarcoma , myxoid malignant fibrous histiocytoma , low - grade fibromyxoid sarcoma , myxoid chondrosarcoma , myxoid peripheral nerve sheath tumors , dermatofibrosarcoma protuberans and metastatic adenocarcinomas . the clinical and the prognostic significance of mucin deposition in melanomas is challenging due to presence of myxoid material both in primary benign or malignant tumors . some authors claimed that mast cells and secretion of transforming growth factor beta stimulates fibroblast secretion of mucin contributing to the tumor s invasive potential ; however , in the absence of compelling contrary data , the current series of cases suggests that myxoid stroma is more significant in diagnosis rather than prognosis of myxoid melanoma . although the real importance of myxoid changes in tumors is not well known , awareness of this stromal pattern in malignant melanomas may prevent misdiagnosis and therapeutic errors .

myxoid melanoma is a rare variant of melanoma , which is characterized by atypical spindle cells and dense mucin deposition in dermis . this tumor is usually seen in elderly people with a similar progress in other variants of melanoma.a 28-year - old male presented to our outpatient clinic with a 6-month history of a slowly growing asymptomatic pink lesion on his arm . dermoscopic examination revealed pink - white cristalline structures and blue - grayish ovoid globules . the lesion was totally excised with initial diagnosis of basosquamous carcinoma , amelanotic melanoma and basal cell carcinoma . histopathological examination was consistent with myxoid melanoma.we present this case due to the rarity of myxoid melanoma and occurrence at such a young age .

giant inflammatory ( filiform ) polyposis is an uncommon benign lesion and is usually associated with inflammatory bowel disease ( ibd ) . long - term inflammation of the colonic mucosa during chronic ibd with alternating periods of ulceration and healing may lead to the formation of finger - like projections [ 1 , 2 ] . in rare cases , a giant inflammatory polyposis forms a large tumor mass [ 3 , 4 , 5 , 6 , 7 ] . on colonoscopy and radiologic studies , numerous filiform polyps appear as a mass of worms or as a fungating mass ; hence , this condition is easily confused with cancer . inflammatory polyps or pseudopolyps are the most common lesions observed both in ulcerative colitis ( uc ) and crohn 's disease ( cd ) [ 8 , 9 , 10 , 11 , 12 ] . moreover , in some cases , the polyps contain both mucosal and submucosal tissue , indicating initial inflammatory involvement of the deeper bowel layers . they are composed of a central core of submucosal connective tissue coated by normal , non - inflamed mucosa . here , we report the case of a patient with uc with large tumors obstructing the transverse and descending colon , who presented with severe diarrhea and melena . a 25-year - old japanese man with an uc history of 2 years and 6 months was successfully treated with prednisolone . the disease was in remission and his symptoms had been relieved . however , the disease flared up and the patient was admitted to our hospital because of severe abdominal pain and bloody diarrhea . physical examination revealed direct soreness and masses in the upper and left lower abdominal sites . blood examination revealed anemia ( hemoglobin level 5.5 g / dl [ normal 11.515.0 ] ) , hypoproteinemia ( protein level 4.6 g / dl [ normal 6.78.3 ] ) and hypoalbuminemia ( albumin level 1.9 g / dl [ normal 3.85.3 ] ) . computed tomography ( ct ) imaging showed bowel wall thickening of the transverse and descending colon , which raised suspicion of wall thickening of several segments of the small bowel . the ct scan also demonstrated localized high - density areas in the lumen of the transverse and descending colon ( fig . a colonoscopy revealed a large mass with numerous white - pale reddish polyps of complex shape in the descending colon . based on this examination , colon carcinoma was strongly suspected , and several biopsies were performed . histology of the examined sections indicated uncharacteristic inflammatory changes in the mucosa , but no cellular dysplasia . , we observed one tumor measuring 23 18 cm in the transverse colon and another measuring 14 13 cm in the descending colon . there were no obvious areas of ulceration , although each tumor had a coral - reef - like surface with numerous soft , finger - like polyps ( up to 5 cm in diameter ) projecting into the lumen . the cross - section of the tumors showed that narrow strings of tissue were interconnected , forming multiple , variably sized spaces inside the tumors ( fig . 2 ) . the surrounding fat tissue was unaffected , and no suspicious lymph nodes were detected . microscopic examination revealed that the tumors comprised strings of fibrotic connective tissue , lined by inflamed colonic mucosa , and the surrounding spaces were filled with fecal and mucoid materials . a fibrovascular core and inflammatory polyposis were evident from the submucosa to the proper muscular layer and the submucosa had partially disappeared in both the elevated and the depressed lesions . the polyps contained regenerative and hyperplastic muscularis mucosa with an arborized and thickened configuration ( fig . the crypt architecture was normal , and no epithelial atypia of the polyps was noted . the mucosal inflammation consisted of lymphocytes , plasma cells , eosinophils and lymphoid follicles . neutrophil infiltration , cryptitis , crypt abscess , which is characteristic of active uc , and paneth cell metaplasia were found in the transverse colon ( fig . sections through the bowel wall near the mass showed colonic mucosa with regenerative features , including architecturally mildly distorted glands , but without active inflammatory changes ( fig . finally , histopathological examination of the resected colon led to the diagnosis of giant inflammatory ( filiform ) polyposis associated with uc . inflammatory polyps are a common complication in patients with ibds such as uc and cd , accounting for approximately 1020% of all cases . inflammatory polyps may originate from the regenerative mucosa in the remission stage after an acute recurrence of uc or cd . in rare cases , numerous large - sized polyps are present , and this condition is known as giant inflammatory ( filiform ) polyposis [ 8 , 9 , 10 , 11 , 12 ] . these polyps are associated with cd in approximately two - thirds of cases and with uc in one - third of cases . giant inflammatory polyposis can be localized in one segment of the colon , or numerous polyps can be diffusely involved in the entire colon . the transverse colon is the most common site , followed by the sigmoid and descending colon , the cecum and the splenic and hepatic flexures . in our case , the clinical features of the reported cases indicate that the time from the initial diagnosis of uc to confirmation of giant inflammatory polyposis ranged from 3 to 276 months . in our patient patients may present with various symptoms , including anemia , weight loss , cramping abdominal pain , diarrhea , passage of blood through the rectum and colonic obstruction . most patients go undiagnosed until they develop signs and symptoms of obstruction , hemorrhage and anemia [ 1 , 2 , 14 ] . the pathogenesis of giant inflammatory polyposis is considered to result from enlarged mucosal tags , caused by repeated peristalsis and fecal stream . giant inflammatory polyposis may be related to postinflammatory regeneration or hyperplastic proliferation of the colonic mucosa between ulcerations . the histopathological features include inflammatory infiltrates overlying the muscularis mucosae , deep fissure - like ulcers , chronic mucosal inflammation with lymphoid hyperplasia and nerve hyperplasia in the surrounding mucosa [ 1 , 2 , 4 , 5 , 6 , 15 ] . giant inflammatory polyposis in uc may be a consequence of severe inflammation rather than of increased duration of the disease . in summary , we present the case of a japanese patient with uc who was diagnosed with giant inflammatory polyposis localized in the transverse and descending colon . severe ulcerative inflammation and its repair process may have caused the development of the giant inflammatory polyps .

we report a unique case of giant obstructing inflammatory polyposis associated with ulcerative colitis ( uc ) . a 25-year - old japanese man with an uc history of 2 years and 6 months was referred to our institution because of diarrhea and melena . his computed tomography scan showed marked dilation of the transverse and descending colon ; therefore , we performed total colectomy . macroscopic evaluation of the excised specimen indicated constricting lesions with giant polyposis in the transverse and descending colon . the polyposis consisted of narrow worm- or noodle - like polyps that bridged over the irregular ulcers . histologic evaluation of the excised specimen indicated transmural inflammation with a thickened proper muscular layer overlaid with inflammatory polyposis . based on these data , a diagnosis of giant inflammatory polyposis should be considered in patients who have had uc . although giant inflammatory polyposis is considered benign , surgical treatment may be indicated to avoid serious complications .

unilateral absence of pulmonary artery ( uapa ) is a rare congenital abnormality , with an estimated prevalence of 1 in 200,000 . some patients with uapa are totally asymptomatic while others may have severe pulmonary hypertension , hemoptysis , congestive heart failure , and cyanosis . we report a 2.5-year - old girl with congenital absence of the right pulmonary artery with associated congenital cystic adenomatoid malformation ( ccam ) of the right lower lobe , patent ductus arteriosus ( pda ) , and atrial septal defect ( asd ) , who presented with ortner 's syndrome due to severe pulmonary hypertension . a 2.5-year - old girl presented with hoarseness of voice noticed since 3 months of age , breathlessness for the past 15 days and failure to thrive . she had been admitted elsewhere for lower respiratory tract infection at 3 months of age . the child was noticed to have a weak cry and an exaggerated suck - rest - suck cycle and sweating over the forehead while feeding . pulse oximetry in room air showed an oxygen saturation varying between 60% and 70% in all four limbs . weight and height were 7 kg and 77 cms , respectively both below the third percentile for age and sex . an ejection systolic murmur grade 3 was heard in the right parasternal region in the fourth and fifth intercostal spaces . the liver was palpable 2 cm below the right costal margin in the mid - clavicular line . chest x - ray [ figure 1 ] revealed cardiomegaly with a cardio - thoracic ratio of 0.6 and deviation of the trachea and mediastinum to the right . two - dimensional ( 2d ) echocardiography showed decreased flow in the right pulmonary artery , a small asd with a right - to - left shunt , and a dilated right atrium and right ventricle with severe tricuspid regurgitation , suggestive of severe pulmonary hypertension . multiple detector computerized tomography aortogram [ figure 2 ] confirmed the findings of asd with pulmonary hypertension , absent right pulmonary artery and hypoplastic right lung with small cystic lesions suggestive of ccam in the right lower lobe . chest x - ray posterioranterior view showing cardiomegaly and shift of trachea and mediastinum to the right multiple detector computerized tomography aortogram showing absent right pulmonary artery , and cystic lesions in the right lower lobe suggestive of congenital cystic adenomatoid malformation ( arrow ) of lung at admission , the patient was started on oxygen , furosemide , enalapril and intravenous cefotaxime , on a provisional diagnosis of congenital cyanotic heart disease with increased pulmonary blood flow , lower respiratory infection , and congestive cardiac failure . despite these measures , there was persistent hypoxemia and worsening of cardiac failure in the form of tachycardia and bilateral basal crepitations . the child was intubated and ventilated and started on pressors , but sustained a cardiac arrest on the 4 hospital day from which she could not be resuscitated . complete arrest of pulmonary artery supply results in the arrest of early bronchial development leading to agenesis of the affected lobe or segment . pulmonary agenesis is usually unilateral , right sided absence of pulmonary artery being more common . more than 50% of children with pulmonary agenesis have associated congenital anomalies that involve the cardiovascular ( pda and patent foramen ovale ) , gastrointestinal , skeletal , and genitourinary systems . our patient had asd and pda . while some patients with uapa are totally asymptomatic , others may have severe pulmonary hypertension , hemoptysis , congestive heart failure , and cyanosis . chest x - ray may show an absent hilar shadow , a shrunken affected lung , and shift of the mediastinum to the affected side . an early interruption in the development of the pulmonary artery could result in the continued development of the primitive capillary supply to a region of the lung with resultant abnormal development of the supplied region . the magnitude of the insult would determine the exact development of the affected lung tissue and final blood supply , resulting in pulmonary sequestration , ccam , or a combination of the two lesions . the incidence of pulmonary hypertension in patients with isolated uapa varies between 18% and 44% . in patients with uapa with pda as in our patient , the incidence of pulmonary hypertension was observed to be as high as 86% , those with pulmonary hypertension dying at an early age . ortner syndrome or cardiovocal syndrome refers to hoarseness of voice due to recurrent laryngeal nerve paralysis secondary to cardiovascular disease . this syndrome was first described by ortner in 1897 in two patients who had mitral stenosis and left recurrent laryngeal nerve paralysis . the syndrome has since been described in adults with various cardiovascular disorders , but reports in children are less common . the pulmonary artery , enlarged due to pulmonary hypertension , has been implicated as the main mechanism of nerve injury . fetterolf and norris studied the anatomic relations of the left recurrent laryngeal nerve in cadavers and concluded that the nerve must be squeezed between the enlarged left pulmonary artery and the aorta or ligamentum arteriosum . unilateral absence of pulmonary artery should be considered in the differential diagnosis of children who present with cyanosis , pulmonary hypertension , or recurrent lower respiratory tract infections .

we report a 2.5-year - old girl who presented with hoarseness of voice since 3 months of age and failure to thrive . chest x - ray showed cardiomegaly with a deviation of the trachea and mediastinum to the right side . two - dimensional echocardiography showed decreased flow across the right pulmonary artery , a small atrial septal defect ( asd ) with a right - to - left shunt , and a dilated right atrium and right ventricle with severe tricuspid regurgitation suggestive of severe pulmonary hypertension . a silent large patent ductus arteriosus was also seen . multiple detector computerized tomography aortogram confirmed the findings of absent right pulmonary artery and hypoplastic right lung with small cystic lesions suggestive of congenital cystic adenomatoid malformation in the right lower lobe . hoarseness of voice was due to the left vocal cord palsy probably secondary to severe pulmonary hypertension ( ortner 's syndrome ) .

in this issue of critical care , kao and colleagues consider whether open lung biopsy ( olbx ) can assist in the management of patients with acute respiratory distress syndrome ( ards ) . clinical outcome in ards remains poor despite substantial advances in our understanding of the biology of this syndrome . although limiting transpulmonary pressure can clearly prevent worsening of ards , no other major therapeutic advances with proven benefit have occurred in this area . progress has been limited potentially due to the heterogeneous phenotypes that are known to underlie the american european consensus definition of this disease . thus , methods to improve diagnostic specificity are likely to be helpful in making progress . olbx has been used for years as a method of defining the underlying pathology in patients with lung disease . while its role has become established in the setting of interstitial lung disease , its utility and safety are more controversial in critically ill patients . proponents of olbx argue that knowledge of underlying etiology can be helpful in defining the best course of treatment . in addition , the risk of biopsy in experienced hands is fairly low if adequate precautions are taken . opponents of olbx cite the lack of specific therapies for underlying etiologies of ards and believe that defining the underlying mechanism of injury is largely academic . a similar discussion has taken place in the interstitial lung disease arena , where some advocate the demonstration of usual interstitial pneumonitis among patients with idiopathic pulmonary fibrosis , whereas others believe that a therapeutic trial of steroids in the majority of patients is justifiable until new therapeutic strategies emerge . the work by kao and colleagues supports the existing literature that open lung biopsy is fairly safe and frequently revealing in the context of ards . first , the authors corroborate prior reports that the underlying pathology in clinical ards is often a pattern other than diffuse alveolar damage or fibro - proliferation . of note , this and prior studies were retrospective analyses making the generalizability of these findings difficult to define . without knowing the total number of ards cases potentially eligible for biopsy , we have no easy way to know how common the observed abnormalities would be in an unselected ards population . second , the authors found minimal morbidity attributable to the surgical procedures that their patients underwent . these data support the existing literature that , in experienced hands , olbx can be safely performed in carefully chosen patients . the risk of bronchopleural fistula was fairly low in the present study , which may reflect the use of protective mechanical ventilation . we have recently observed that high pressures measured at the airway opening are strongly predictive of prolonged bronchopleural fistula risk following lung biopsy in ards . thus , attention to mechanical ventilator settings may be one factor that led to the low risk of this procedure . nearly 75% of patients had changes made in their therapeutic management due to findings from olbx . whether these changes were helpful to the patient is not entirely clear due to the lack of a control group however , at least 14 patients ( 11 with infections , 1 with hypersensitivity pneumonitis , and 2 with pulmonary edema ) had a disorder found for which accepted therapies exist . interestingly , the most common change in management recorded in response to olbx results was the institution of glucocorticoid therapy . the role of glucocorticoid therapy in ards has been controversial , with some smaller studies showing benefits whereas other larger studies demonstrated no important benefit . a number of critiques have emerged after the recently published new england journal of medicine trial examining the role of steroids in persistent ards , leading some to speculate that , despite the negative results of that trial , some ards patients may still benefit from anti - inflammatory therapy . in this recent study , more than 95% of patients were excluded prior to enrollment , leading to results that may not be generalizable to the overall ards population . the most common reason for exclusion was glucocorticoid therapy , yielding the possibility that the best candidates for steroid therapy ( from both an efficacy and safety perspective ) were excluded from the study . in addition , the frequent use of paralytics ( in up to 50% of steroid treated participants ) and marked hyperglycemia ( mean values in excess of 200 mg / dl ) may have contributed to avoidable complications of steroid therapy . thus , the frequent re - intubations and neuromyopathies that occurred in this recent study may have offset the potential benefits of steroid therapy . regardless , the stratification of patients likely to benefit from steroid therapy , while avoiding the potential morbidity of pharmacological therapies and other intensive care unit measures ( including mechanical ventilation ) is likely to be a successful strategy . future studies that aggressively limit the side effects of steroids and that examine treatment response stratified by olbx findings may demonstrate subgroups of patients that derive important benefit from this therapy . in the future , biomarkers that could be defined either in the serum or by bronchoalveolar lavage would be preferable to olbx to stratify the likelihood of benefit from steroid therapy . such biomarkers may help define the underlying pathobiology and so become a surrogate for olbx in assessing the steroid responsiveness of the disease . another class of biomarkers that may prove useful in the management of ards patients would be ones that provided information on the intrinsic steroid responsiveness of the patient . the search for genetic polymorphisms that predict individual responsiveness to steroid therapies is well underway in other conditions such as asthma and ulcerative colitis . both types of biomarkers would aid treatment decisions by better defining subgroups most likely to benefit from steroid therapy . thus , further work is clearly needed to determine whether individualized therapy will improve outcome in various subgroups of ards patients .

progress in the treatment of acute respiratory distress syndrome ( ards ) has been slow , perhaps in part due to the heterogeneity in the biology underlying this syndrome . open lung biopsy is a feasible approach to define various subcategories of underlying histology . in experienced hands , with careful selection of patients and close attention to details of critical care management , including mechanical ventilator settings , the procedure is safe even in patients with severe disease . however , further work is needed to define which patients , if any , experience a beneficial effect on outcome from this procedure . more research is needed on assessing efficacy of potential therapies within histologically defined subgroups . in the future , various biomarkers may be available to non - invasively classify ards patients from the standpoint of responsiveness to various therapies , such as gluco - corticoids .

to report an unusual case of multifocal bacterial keratitis that despite success - ful treatment caused chronic ocular hypertension . a 67-year - old woman with unilateral multifocal keratitis and no previous ocular pathology was admitted to our hospital . corneal scrapings and conjunctival samples were obtained for culture and the patient received intensive therapy with fortified vancomycin and tobramycin eye drops . the cultures demonstrated two strains of staphylococcus epidermidis , one resistant to ciprofloxacin and both sensitive to vancomycin . treatment was effective and gradually discontinued after total cessation of the inflammatory activity . during the follow - up period , the patient developed late and persistent ocular hypertension of unknown etiology , in absence of any detectable inflammation or complication , and received permanent antiglaucoma therapy . patients with multifocal bacterial keratitis may need intraocular pressure monitoring , even after complete infection healing . staphylococcus is a common gram - positive bacterium causing keratitis that tends to present with a focal and well - defined white or yellow - white infiltrate . during the infection , corneal inflammation can lead to neovascularization and scarring , while internal ocular inflammation can cause synechia formation , elevated intraocular pressure and cataract [ 1 , 2 ] . several staphylococcal strains have been reported resistant to topical quinolone therapy [ 3 , 4 ] . we report an unusual case of quinolone - resistant multifocal staphylococcal keratitis without a history of previous ocular pathology , which caused chronic intraocular pressure elevation despite successful keratitis treatment and complete resolution of external and internal ocular inflammation . a 67-year - old woman presented in the emergency section of our department with gradual onset of redness , tearing , photophobia and a 4-day history of blurred vision in her right eye . there was no history of contact lens wear , previous ocular disease , trauma or surgery . examination of the right eye revealed visual acuity of counting fingers , intense conjunctival injection , mild corneal edema and three corneal ulcers of different extension ( 15 mm in diameter ) . a moderate aqueous flare was noted in the anterior chamber without presence of hypopyon or pupillary synechiae ( fig . 1 ) . intraocular pressure and fundus were normal , and there were no pathological findings in her left eye . corneal scrapings and conjunctival samples were obtained from the right eye and sent to the laboratory for culture . the patient was hospitalized and received empirical treatment with fortified vancomycin + tobramycin ( voncon , lilly + tobrex , alcon ) eye drops every 30 min the first day , every hour the second day and afterwards every 2 h. topical cyclopentolate ( cyclogyl , alcon ) 3 times daily was also administered . the cultures demonstrated the presence of two strains of coagulase - negative staphylococcus epidermidis , one resistant to ciprofloxacin and both sensitive to vancomycin . one week after treatment implementation , the patient reported partial relief from her initial symptoms . a considerable reduction of the extension of corneal ulcers was noted , though aqueous flare and intraocular pressure increased ( 32 mm hg ) and corneal neovascularization appeared at the limbus adjacent to the corneal ulcers . treatment was modified to topical vancomycin , dexamethasone ( maxidex , alcon ) and cyclopentolate initially 3 times daily , with a progressive tapering scheme during the following 3 weeks . after the 3-week - period , the corneal ulcers were completely healed ; there was no conjunctival injection , no visible aqueous flare but only a mild scarring at the superior limbus ( fig . two months later , a persistent ocular hypertension ( 2628 mm hg ) of unknown etiology and without any external or internal ocular inflammation was noted in the right eye at three consecutive visits . a goldmann contact lens was used to perform a 360 gonioscopy that did not reveal any pathological findings . intraocular pressure was normal in the left eye and corneal pachymetry was normal in both eyes . topical brinzolamide was restarted and follow - up was continued monthly . for the next 6 months , intraocular pressure in the right eye fluctuated within normal limits and no inflammatory recurrence was observed . occasionally , staphylococcal keratitis can present with predominantly multifocal epithelial infiltration , especially in the setting of hydrophilic contact lens wear or after laser in situ keratomileusis . multiple foci of abscesses resemble fungal satellite lesions [ 1 , 5 ] . in the present case , furthermore , we did not detect any predisposing factors for chronic intraocular pressure elevation , such as history of glaucoma or ocular hypertension , trauma , relapsing inflammation and anterior or posterior synechiae . the existence of aqueous flare in the anterior chamber could explain the temporary intraocular pressure rise diagnosed in the second week , though after total cessation of the inflammatory activity the intraocular pressure returned to normal values as expected . steroid - induced ocular hypertension does not seem to be relevant since steroid treatment was of limited duration , low dosed and gradually discontinued . a possible explanation for the late and persistent intraocular pressure elevation may be a permanent damage of the trabecular meshwork caused by staphylococcal toxins . despite normal appearance of the iridocorneal angle on gonioscopy , invisible microscopic changes could not be excluded . the resistance of one s. epidermidis strain to ciprofloxacin is in accordance with previous reports and indicates that microbial culture is necessary in cases of extensive bacterial corneal ulcers [ 3 , 4 ] . furthermore , it also shows that an initial empirical treatment with a combination of fortified topical antibiotics may be superior to topical quinolone monotherapy in these cases . however , further evidence is required to support the above hypothesis since there are studies showing equivalence of fluoroquinolone monotherapy to fortified medications in microbial keratitis [ 6 , 7 ] . unfortunately , it was not possible for our laboratory to test the sensitivity of the ciprofloxacin - resistant strain to newer - generation quinolones , which could have had better activity against these gram - positive organisms . in conclusion , the present case demonstrates that in patients with multifocal keratitis , differential diagnosis between fungal and bacterial infection is critical for successful treatment . besides treatment , patient follow - up and intraocular pressure monitoring may be needed , even after complete infection healing and resolution of inflammatory signs .

purposeto report an unusual case of multifocal bacterial keratitis that despite success - ful treatment caused chronic ocular hypertension.methodsa 67-year - old woman with unilateral multifocal keratitis and no previous ocular pathology was admitted to our hospital . corneal scrapings and conjunctival samples were obtained for culture and the patient received intensive therapy with fortified vancomycin and tobramycin eye drops.resultsthe cultures demonstrated two strains of staphylococcus epidermidis , one resistant to ciprofloxacin and both sensitive to vancomycin . treatment was effective and gradually discontinued after total cessation of the inflammatory activity . during the follow - up period , the patient developed late and persistent ocular hypertension of unknown etiology , in absence of any detectable inflammation or complication , and received permanent antiglaucoma therapy.conclusiondifferential diagnosis between fungal and bacterial infection is critical in cases of multifocal keratitis . patients with multifocal bacterial keratitis may need intraocular pressure monitoring , even after complete infection healing .

stevens johnson syndrome ( sjs ) is thought to be a hypersensitivity complex affecting the skin and the mucous membranes . a new anticonvulsant , oxcarbazepine , which is structurally related to carbamazepine ( cbz ) , was introduced for use in patients with epilepsy . drug hypersensitivity reactions can occur with most drugs , although the frequency , severity , and clinical manifestations vary . drug hypersensitivity can be defined as an inappropriate immune response leading to tissue damage from an otherwise nontoxic agent . drug hypersensitivity reactions to benzodiazepines often fall into the category of type b ( or bizarre ) adverse drug reactions , according to the classification proposed by rawlins and thompson . the incidence of hypersensitivity varies according to the drug , the disease being treated , and the ethnicity of the patient . drug response ( including drug hypersensitivity ) is a multifactorial and multigenic process , dependent on a complex interaction between multiple genes and the environment [ figure 1 ] . each gene contributes to the risk of developing the hypersensitivity reaction , but each individual gene is neither necessary nor sufficient by itself to cause the reaction . a female patient of 38 years with a history of drug allergy was complaining of fever , sore throat , and fatigue , at the time of admission . she was administered oxcarbazepine for the management of right partial bronchial seizure due to left parasagittal mass lesion following which she developed papular rashes all over the body and diagnosed as sjs . in this case , during the first week , we used 600 mg / day oxcarbazepine for seizure control , and then increased the dose after 3 days to 900 mg / day . after 10 days of treatment , ulcers and other lesions begin to appear in the mouth and lips along with the genital and anal regions . ulcers in the mouth are usually extremely painful and reduce the patient 's ability to eat or drink . high fever and multiple maculopapular rashes were found over the patient 's face and neck initially on the 12 day after taking oxcarbazepine . she was brought to our emergency department and admitted under the presumed diagnosis of sjs . laboratory investigations showed leukocytosis ( wbc , 14660/l ; reference value , 4,000 - 10,000/l ) , and elevated c - reactive protein ( 59.30 g / ml ; reference range , 0 - 5 g / ml ) . after obtaining informed consent , we carried out genotyping and took photos of the patient . there was marked liquefactive degeneration in the lower half of the epidermis with some dyskeratotic keratinocytes . the dermis showed predominant cd8 + lymphohistiocytic infiltration around the blood vessels and scanty eosinophils . after corticosteroids ( iv dexamethasone 1.0 mg / kg body weight ) and antihistamine treatment for 10 days , the patient improved and was discharged from the hospital . anticonvulsant hypersensitivity syndrome is a potentially fatal drug reaction with cutaneous and systemic reactions ( incidence , 1 in 1000 to 1 in 10,000 exposures ) to the arene oxide - producing anticonvulsants phenytoin , cbz , and phenobarbital sodium . cbz and its derivatives are widely used anticonvulsants that can cause rashes in up to 10% of patients , and in occasional cases , this may be the precursor to the development of a hypersensitivity syndrome characterized by systemic manifestations such as fever and eosinophilia . the diagnosis of sjs is based on clinical manifestations with acute onset of rapidly expanding targetoid erythematous macules , necrosis and detachment of the epidermis along with erythema , erosions , and crusting of two or more mucosal surfaces . our patient had skin targetoid erythematous rashes and mucosa involvement 2 weeks after starting oxcarbazepine treatment . during these 2 weeks the skin pathology finding revealed lymphohistiocytic infiltration around the blood vessels and scanty eosinophils , which was consistent with sjs . the patients usually develop a hypersensitivity reaction between 2 and 12 weeks after starting medicine . it has been postulated that metabolites and not the parent drug are the causal agents . one of the first reports showed that hla - b*1502 was present in 100% of cbz - induced patients with sjs but in only 3% of patients tolerating cbz and in 9% of the general population . other studies have confirmed these results in han chinese and in the thai population . in this case , we used a dose of 600 mg / day and then titrated it to 900 mg / day . it has been reported that higher daily doses of drugs are associated with an increased risk of sjs than lower doses , which is the case for allopurinol . however , lam et al . found that the early use of short - term systemic steroids for 35 days lacked any significant side effects and did not increase mortality or morbidity . no sequels were found during 3 months of follow - up . compared with other categories of drugs , such as antibiotics and nsaids , antiepileptic therapies are associated with a high incidence of sjs and toxic epidermal necrolysis ( ten ) . case reports by chen et al . suggest that identification of such genetic factors is important , not only to realize the prospect of developing preventive strategies but also to learn about the mechanisms of these reactions , which may ultimately lead to other preventive strategies through better drug design and to better treatment strategies for patients who develop the reactions .

stevens johnson syndrome ( sjs ) is a rare immunologic reaction that may involve skin or various mucosal surfaces . the etiology may range from multiple pharmacologic agents to viral infections . associated findings can range from minimal skin and mucosal involvement to extensive dermal exfoliation , nephritis , lymphadenopathy , hepatitis , and multiple serologic abnormalities . we report a female patient of 38 years with a history of drug allergy who was administered oxcarbazepine for the management of right partial bronchial seizure due to left parasagittal mass lesion following which she developed papular rashes all over the body and diagnosed as sjs . although carbamazepine ( cbz ) is the most common cause of sjs , a new anticonvulsant , oxcarbazepine , which is structurally related to cbz , has been shown to induce sjs .

this sticky , greenish - brown product has different compositions depending on the location of the bees and what trees and flowers they have access to . propolis from turkey or egypt will not have the same chemical properties as propolis from europe or brazil . this is because it is very difficult for researchers to come to general conclusions about its health benefits . caffeic acid phenethyl ester ( cape ) [ figure 1 ] is one of important compounds found in propolis that has antiviral , antioxidant , anti - inflammatory , antiproliferative , antitumor , and immunomodulatory effects . this marvelous compound has been used to prevent oxidative stress - based deterioration in cells / tissues / organs in both cell culture and experimental animals . lately , the protection of cape on central and peripheral nervous system as well as a reproductive system have been extensively reviewed [ 3 - 5 ] . it has extensively been used to treat a broad of malignancies including hodgkin s and non - hodgkin s lymphoma , burkitt s lymphoma , chronic lymphocytic leukemia , ewing s sarcoma , breast cancer , testicular cancer , etc . it has toxic effects in almost every system in the human body including the heart , liver , and kidney of which mostly due to its structural properties prone to induce oxidative stress in vitro and in vivo . the chemical illustration of caffeic acid phenethyl ester this study aimed to collect data and compare the protective effects of propolis and cape against cp - induced injury in animals . , ameliorative effect of propolis against cp - induced toxicity in mice was studied by el - naggar et al . . it throws light on the side effects of a common anticancer agent , cp , used in the treatment of various malignancies and possible remedies to prevent that type of side effects in vital organs such as liver and kidney . uysal et al . conducted an experimental animal study to determine protective role of cape on cp - induced hemorrhagic cystitis ( hc ) . while cp - induced hc lead to increase in superoxide dismutase , catalase , and malondialdehyde activities / levels , cape significantly reduced these parameters showing the protective effects . in addition to this biochemical effects , cape also ameliorates edema , hemorrhage , inflammation , and mucosal ulceration of cp - induced hc . we published a review article about toxicities of some therapeutic compounds and the protective effect of cape on chemotherapy- and radiotherapy - induced toxicity . we have shown that cape has protective effects on oxidative stress - induced toxicities by doxorubicin ( nephrotoxicity ) , cisplatin ( nephrotoxicity , ototoxicity , and hepatotoxicity ) [ 10 - 13 ] , and bleomycin ( lung fibrosis ) . currently , there is no medically recommended dose for propolis , since the mixture of propolis is subjected to change depending on its source . the most successful medical application field of propolis is beauty and skin care , especially in acne vulgaris because of its antibacterial , antiviral , antifungal , and anti - inflammatory properties . despite the fact that both water and ethanolic extractions of propolis have been used in the in vivo and in vitro experiments , water - soluble extracts of propolis exhibit higher antioxidant and inhibitory activities as compared ethanolic extract in vitro . in this perspective , even though the extraction method selection is dependent on the authors desire , it would be expected for authors to study propolis for their experiments comparatively by selecting propolis extracted by both extraction methods . cape is the most potent antioxidant agent of propolis mixture having free radical scavenging activity and potent inhibition of nf-b . so , the protective antioxidant effect of ethanol extract of propolis on organs depends mostly on cape rather than other polyphenolic compounds such as flavonoids , phenolic acids , and their esters [ figure 2 ] . cape was shown to completely block the production of reactive oxygen species in human neutrophils and in the xanthine / xanthine oxidase systems at 10 m concentration by its competent antioxidant capacity . indeed , cape has a regulatory effect on antioxidant enzyme activities such as catalase , superoxide dismutase , and glutathione peroxidase [ figure 2 ] . proposed mechanism of how cyclophosphamide - induced oxidative stress is blocked by antioxidant enzymes in several parts of hepatocytes and renal cells and how cape shows its protective effects against oxidative stress . aas : amino acids , cape : caffeic acid phenethyl ester , cat : catalase , fe : ferrous iron , gpx : glutathione peroxidase , gsh : reduced glutathione , gr : glutathione reductase , gssg : oxidized glutathione , h2o : water , nadp : oxidized nicotinamide adenine dinucleotide phosphate , nadph : reduced nicotinamide adenine dinucleotide phosphate , o2 : molecular oxygen , o2 : superoxide anion radical , oh : hydroxyl ion , oh : hydroxyl radical , onoo : peroxynitrite , no : nitric oxide , nos : nitric oxide synthase , pufa : polyunsaturated fatty acid , sod : superoxide dismutase it has been shown that cape application to the rats modifies the enzyme activity of cytochrome p450 ( cyp ) isoforms involved in the activation of diethylnitrosamine such as cyp1a1/2 and cyp2b12 . furthermore , treatment with cape of carbon tetrachloride - induced hepatotoxicity in mice blocks cyp2e1-mediated ccl4 bioactivation and protects against fas / fasl - mediated apoptosis . it will be very interesting to see the effect of cape on cyp2b6 , which constitutes 3 - 6% of total hepatic cyp content and metabolizes several pharmaceuticals including cp . to achieve this , further studies on the every single bioactive constituent of propolis such as cape and some other polyphenols are necessary to identify interactions mediating their biological effects on cyp2b6 , since there are roughly 150 different polyphenolic compounds within propolis . as a conclusion , studying propolis to prevent cp - induced oxidative stress in animals has several limitations since the proposed effect can not be specified to one or several molecules within the mixture . in that case , every single bioactive constituent of propolis needs to be studied to show the source of real effects and the molecular mechanisms of this effects .

propolis is a mixture having hundreds of polyphenols including caffeic acid phenethyl ester ( cape ) . they have been using in several medical conditions / diseases in both in vitro and in vivo experimental setup . cyclophosphamide ( cp ) has been used to treat a broad of malignancies including hodgkin s and non - hodgkin s lymphoma , burkitt s lymphoma , chronic lymphocytic leukemia , ewing s sarcoma , breast cancer , testicular cancer , etc . it may cause several side effects after treatment . in this mini review , the protective effects of propolis and cape were compared each other in terms of effectiveness against cp - induced injuries .

therapeutic hypothermia has been shown to provide neuroprotection against ischemic injury after cardiac arrest in in vitro and in vivo models . in the previous issue of critical care , meybohm and colleagues demonstrate that cardiac arrest triggers the release of cerebral inflammatory cytokines in pigs ' cerebral cortex . . the combination of hypothermia with sevoflurane post - conditioning does not confer additional anti - inflammatory effects compared with hypothermia alone . cardiac arrest remains the leading cause of death in the us and europe , with an out - of - hospital cardiac arrest survival - to - discharge rate of less than 10% . in - hospital cardiac arrest presents a dismal prognosis . according to a large in - hospital registry , the survival - to - discharge rate is 18% , whereas that of a developing country is 6.9% . without prompt care when immediate care is available and victims are successfully resuscitated , the majority of these initial survivors subsequently suffer crippling neurologic injury or die in the few days following the cardiac arrest event . thus , improving survival and brain function after initial resuscitation from cardiac arrest remains a critical challenge . therapeutic hypothermia , introduced more than six decades ago , remains an important neuroprotective factor in cardiac arrest . laboratory studies have demonstrated that cooling after resuscitation from cardiac arrest improves both survival as well as subsequent neurologic and cardiac function and has few side effects . these findings have been reproduced using a variety of cooling techniques in different species , including rats , dogs , and pigs . however , physician use of hypothermia induction in patients resuscitated from cardiac arrest is low . in 2003 , abella and colleagues reported that 87% of us physicians did not use therapeutic hypothermia following cardiac arrest . various reasons for non - use were cited : 49% felt that there were not enough data , 32% mentioned lack of incorporation of hypothermia into advanced cardiovascular life support protocols , and 28% felt that cooling methods were technically too difficult or too slow . in 2002 , a european group demonstrated an improvement in survival - to - discharge rate with favorable neurologic status in cooled patients , compared with normothermic patients surviving after cardiac arrest ( 53% versus 35% , respectively ) , and with no significant adverse events from cooling ; thereafter , induced hypothermia was considered the best practice for patients following cardiac arrest . in 2005 , the american heart association recommended the consideration of therapeutic hypothermia for unconscious adult patients with return of spontaneous circulation following out - of - hospital cardiac arrest due to ventricular fibrillation . in 2008 , binks and colleagues reported that 85.6% of intensive care units in the uk were using hypothermia as part of post - cardiac arrest management . clinical observation demonstrated that tumor necrosis factor - alpha ( tnf ) and interleukin-6 ( il-6 ) protein were increased in cerebrospinal fluid following cardiac arrest . animal studies showed that inflammatory markers were unregulated in rats ' hippocampus tissue and pigs ' serum and myocardial tissue after cardiac arrest [ 8 - 10 ] . meybohm and colleagues go further to demonstrate anti - inflammatory and anti - apoptosis effects of therapeutic hypothermia via the reduction of the upregulation expression of il-1 , il-6 , il-10 , tnf and intercellular adhesion molecule-1 , bcl-2 , and bax mrna and il-1 protein in cerebral cortex after cardiac arrest in a pig model . small reductions in core temperature lead to vaso - constriction and shivering , effectively hindering hypothermia . thus , prevention of vasoconstriction and shivering has become a major goal during induction of therapeutic hypothermia . sevoflurane pre - conditioning and early post - conditioning reduced both cerebral infarct size and neurological defect score , reduced impairment of hippocampus long - term potentiation resulting from myocardial ischemia , and increased nuclear factor inhibitory kappabalpha content in thp-1 cells [ 11 - 13 ] . sevoflurane pre - conditioning preserves myocardial function in patients undergoing coronary artery bypass graft surgery under cardiologic arrest . an in vivo study showed that combination hypothermia with sevoflurane attenuates the inflammatory response during endotoxemia . however , meybohm and colleagues could not provide evidence to support the view that sevoflurane post - conditioning confers additional anti - inflammatory effects in pigs ' cerebral cortex after cardio - pulmonary resuscitation . in summary , meybohm and colleagues provide useful evidence to support the clinical use of therapeutic hypothermia for cardiac arrest , but they did not study the anti - inflammatory effects of sevoflurane in this model . it is even possible that in the setting of clinical practice , anesthetics may not provide significant neuroprotection beyond that which is already being produced by therapeutic hypothermia . thus , at this time , it is difficult to recommend anesthetics for the purpose of neuroprotection in cardiac arrest .

in the previous issue of critical care , meybohm and colleagues provide evidence to support hypothermia as a kind of therapeutic option for patients suffering cardiac arrest . although anesthetics had been used to induce hypothermia , sevoflurane post - conditioning fails to confer additional anti - inflammatory effects after cardiac arrest . further research in this area is warranted .

a 72-year - old patient who had undergone bilateral uneventful cataract surgery 6 years ago , presented with visual loss in her left eye . patient had a medical history of multiple intravitreal and periocular steroid injections for the treatment of recalcitrant uveitis that was diagnosed 21 years ago . her visual acuity decreased to hand motion in left eye , and slit - lamp biomicroscopy revealed in - the - bag iol with an intact posterior capsule , and severe flare in the anterior chamber . an unclear image of macular edema was hardly detected on flourescein angiography ( fa ) that revealed flue images of posterior - segment obscured by media opacity . after obtaining a signed informed consent , we scheduled to perform the intravitreal ozurdex application under the sterile conditions of the operation room . a drop of 0.5% topical proparacaine hydrochloride with a drop of 5% povidone iodine was installed before the patient underwent an uncomplicated intravitreal dexamethasone implant application . after significant regression of inflammatory cells secondary to uveitis , mild macular edema and an epiretinal membrane were precisely demonstrated with both optical coherence tomography and fa at 2 weeks after ozurdex application . on the postoperative 5 week , best corrected visual acuity ( bcva ) was improved to 0.4 logmar , and slit - lamp examination revealed the implant mislocated just behind the iol in an intact capsular bag , although there was no reaction in the anterior chamber , and no corneal edema was observed [ fig it was thought that such implant anteriorly migrated toward into the posterior chamber through weak zonules in the present case as she had a medical history of uneventful phacoemulsification surgery with the implantation of posterior chamber iol . slit - lamp biomicroscopy revealed the dexamethasone implant mislocated just behind the intraocular lens in an intact capsular bag , and localized in the lower center of the visual axis ( white arrow ) any repositioning procedure was not considered since no sign of corneal edema or iop rise was present , as well as patient did not have any complaints although dexamethasone implant mislocated in the lower center of the visual axis . close follow - up was scheduled for the case in order to find out any signs of anterior segment pathology . in the affected eye , bcva and iop were found as 0.5 logmar and 17 mmhg with a quiescent anterior chamber and a clear cornea at the 4 month of postoperative follow - up , besides dexamethasone implant completely degraded . steroid - induced ocular complications such as cataract formation and iop elevation have been more commonly reported according to the accelerating ozurdex application in the treatment of macular edema . anterior migration of dexamethasone implant has also been published as a rare complication in the literature . migration of ozurdex into the anterior chamber was firstly described by pardo - lpez et al . in a patient with iris fixated iol . after the patient had been referred with blurred vision in his left eye at the postoperative 3 week , authors noticed anterior migration of the implant with a diffuse corneal edema . patient had to be undergone corneal transplantation since corneal edema did not resolve even though surgical removal of the implant from the anterior chamber was performed . jonas and schmidbauer reported dislocation of a steroid implant into the anterior chamber in an aphakic vitrectomized eye . vela et al . also reported the migration of ozurdex into the anterior chamber in a patient who previously underwent cataract surgery with iris - claw iol implantation . the anterior migration of the ozurdex implant can cause complications such as secondary corneal decompensation . in these cases , bansal et al . published the migration of the implant into the anterior chamber in three noninfectious posterior uveitic eyes with the history of postlensectomy - vitrectomy aphakia . authors reported that the implant was relocated in the vitreous cavity in two of the cases . nonsurgical management of a dislocated dexamethasone implant into the anterior chamber with supine positioning after pharmacologic pupillary dilation was described by kishore and schaal . published the scleral fixation of dexamethasone intravitreal implant with 10 - 0 nonabsorbable polypropylene suture in an angle - supported iol implanted case in order to prevent the risk of anterior segment complications associated with the migration of such implant into the anterior chamber . it was recommended that dexamethasone implant which migrated into the anterior chamber ought to be removed as soon as possible in cases with incipient corneal edema . on the other hand , no corneal edema was reported in patients with late migration of such intravitreally injected implant . mentioned that only the patients in whom dexamethasone implant anteriorly migrated into the anterior chamber within 3 weeks after the intravitreal application developed corneal edema in their series . any sign of corneal edema also did not occur in our case who was faced with the anterior migration of such implant 5 weeks after the uncomplicated intravitreal application . anterior migration of a dexamethasone implant in eyes without perfect zonular or the posterior capsular integrity after cataract surgery , and with a history of the prior vitrectomy has been well - defined . reported five patients with an anteriorly migrated dexamethasone implant despite within the same lens and capsular status , although they had previous uncomplicated dexamethasone implant injections without any anterior chamber migration . anterior migration of a dexamethasone posterior implant into the anterior chamber through weak zonules was also described in cases with intact posterior capsule . implant was surgically removed from the anterior chamber immediately by daudin and brzin , however turaka et al . reported that , without any surgical intervention , implant was spontaneously relocated back into the vitreous cavity with significant resolution of the corneal edema . herein , we report the first case with anterior migration of a dexamethasone intravitreal implant that mislocated just behind the iol in an intact capsular bag . in the present case , the migrated implant was well tolerated as there was no sign of the corneal complication , iop rise , and anterior chamber reaction . as this is a report of unique case with short follow - up , it is very difficult to comment that mislocation of a dexamethasone intravitreal implant on an intact posterior capsule is an innocent complication . it is mandatory to observe more cases with long follow - up in order to estimate possible side effects of ozurdex implant attached on the posterior capsule .

intravitreal application of ozurdex ( allergan , inc . , irvine , ca , usa ) which is a biodegradable , sustained - release dexamethasone implant has been reported to be effective in the treatment of macular edema . migration of such implant into the anterior chamber has been recently described in cases without perfect zonular or the posterior capsular integrity . herein , we report the first case with anterior migration of ozurdex implant that mislocated just behind the intraocular lens ( iol ) in an intact capsular bag . it is thought that such implant migrated anteriorly towards into the posterior chamber through weak zonules as the present case had a medical history of uneventful phacoemulsification surgery with the implantation of posterior chamber iol . however , the migrated implant was well tolerated since there was no sign of the corneal complication , rise in intraocular pressure , and anterior chamber reaction . close follow - up was scheduled to find out any signs of anterior segment pathology . meanwhile dexamethasone implant completely degraded at the 4th month of postoperative follow - up .

the difficulty with evaluating an intervention once it has become part of established practice is that , like servicing a car in motion , the method is inconvenient and the results unreliable . moreover , the intervention is likely to have acquired both adherents and detractors , thereby ensuring maximal uncertainty while impairing individual equipoise . we are left with performing retrospective observational before - and - after studies , relying on large numbers to minimise confounding . outcomes were obtained from the australia and new zealand intensive care society ( anzics ) database . from a pool of 172 australia and new zealand hospitals , the presence or absence of a medical emergency team ( met ) could be determined in 131 , of which 84 ( 64% ) had established an met . of the 84 hospitals with an met , 24 provided adequate data to the anzics database to determine the number and rate of intensive care unit ( icu ) admissions following an in - hospital cardiac arrest , and the proportion of icu readmissions , one year before and one year after implementing the met . comparisons were also possible with some of the hospitals that had participated in the medical emergency response improvement team ( merit ) study , the only prospective multicentre cluster - randomised study available . the authors found a reduction in the number and rate of post - cardiac arrest icu admissions for both the 47 met hospitals and 16 non - met hospitals during the two - year period . icu readmission rates were unchanged , and there was no reduction in hospital mortality for either group . these findings are consistent with the merit study , which found that adverse outcomes improved in both the met and non - met hospitals . the authors suggest that the introduction of mets has been driven not by evidence of efficacy but by evidence of suboptimal care of acutely ill patients in hospital and an assumption that pre - emptive intensive care would either save lives or permit a dignified death . should we wait 25 years before thrombolysis becomes the established best practice in guidelines and textbooks ? or should we follow nike 's approach and ' just do it ' ? this was what happened with mets , now referred to generically as rapid response teams ( rrts ) . at first sight , the concept would seem to be an eminently sensible response to the problem of suboptimal care of acutely ill hospitalised patients : you take critical care expertise to the patient before , rather than after , multiple organ failure or cardiac arrest occurs . why do we need evidence that neglect or inexpertise should be replaced by timely competent care ? the answer to this question is as complex as the system to which the intervention has been applied . for some intensivists , the met was an unnecessary intrusion into the service they were already providing . for others others were concerned that it would just shift the burden of illness even more onto a service that could not cope . ward staff could be positive , or suspicious ; ' deskilling ' was a common phrase , although it was probably removing responsibility for patient care rather than skills that may never have existed in the first place . the problem is that the health care systems that funded mets did not want to spend additional money on finding out whether they were effective , and those of us involved from the beginning were unable at that time to persuade research funders otherwise . first , the main problem surrounding the entire literature on rrts is that the publications never specify the content of the intervention . an rrt is not an intervention : it is a vehicle for an intervention such as sepsis bundles or early antibiotics or a do - not - resuscitate ( dnr ) order or ( perhaps even more importantly ) education . as in the ( similarly negative ) pac - man study , the use to which the tool is put is largely unknown . given the diffusion of best practice , we can be reasonably confident that non - met hospitals will also have doctors and nurses who want to provide good care and avoid burdensome futile care . second , should we use process or outcome measures for evaluation ? processes of care are important not only because they may alter outcomes ( the destination ) , but because they can change the way in which that outcome is achieved ( the pathway ) . end - of - life care is the obvious example . last week , our outreach nurses called one of us to an acute ward because a junior doctor was unwilling to implement a dnr order for a terminally ill 91-year - old man . we obtained full consensus on treatment limitation , provided comfort care , and contacted the patient 's son , who then spent the few remaining hours by his father 's bedside before death supervened . the alternative scenario would almost certainly still have resulted in a ward death , but without dignity and with less emotional resolution for the son . third , it may be unwise to assume that the context in which the intervention is applied is similar across all hospitals . a well - staffed hospital with excellent senior staff relationships and teamworking might find little benefit from an rrt , whereas in another the converse conditions might prevent an rrt from having any effect on outcomes . differences in patients ' severity of illness could confound the results : further refinements of ward - based measures of severity of illness might help in this respect . nurse - led , doctor - supported outreach care has transformed the way in which we in the uk provide support for acutely ill patients in ordinary wards in terms of relieving some of the workload on intensive care doctors , supporting timely delivery of care , improving pain relief and end - of - life care , enhancing communication , and teaching ward nurses and doctors . these qualitative aspects may not be reflected in immediate changes in mortality or icu readmissions , but they may still be very important to patients . we are aware of john galbraith 's statement that ' faced with the choice between changing one 's mind and proving that there is no need to do so , almost everyone gets busy on the proof ' . but perhaps the real problem is that we have not yet properly defined the content of the intervention , the context in which it is applied , or the research question . anzics = australia and new zealand intensive care society ; dnr = do not resuscitate ; icu = intensive care unit ; merit = medical emergency response improvement team ; met = medical emergency team ; rrt = rapid response team . jfb declares an academic bias towards favouring outreach care as an effective method of improving the quality of acute care .

the philosophy behind medical emergency teams ( mets ) or rapid response teams leaving the intensive care unit ( icu ) to evaluate and treat patients who are at risk on the wards and to prevent or rationalise admission to the icu is by now well established in many health care systems . in a previous issue of critical care , jones and colleagues report their analysis of the impact on outcomes of mets in hospitals in australasia and link this to reports appearing in the world literature .

formulations were prepared using different polymers kollidone sr , cellulose acetate , acrycoat s 100 , methocel k4 m , methocel k15 m , methocel k100 m . drug and polymer in proportion 1:2 , ( drug : polymer ) were dissolved in organic solvent ( ethanol and acetone ) . this clear solution was poured slowly as a thin stream in oil phase ; about 100 ml of liquid paraffin solution with continuous stirring at a speed of 500 rpm using mechanical stirrer at room temperature until complete evaporation of solvent took place . the floating microspheres were collected by decantation , while the non floating microspheres were discarded along with any polymer precipitates . several preformulation trials were undertaken for various proportions of drug and polymer by variation of the ethyl acetate - acetone ratio and dichloromethane - ethanol ratio . kollidone sr , acrycoat s 100 and cellulose acetate were selected as matrixing agent considering its widespread applicability and excellent gelling activity in sustain release formulations and also having the ph - independent and reproducible drug release profile . it was found that kollidone sr microspheres show desirable high drug content , yield , floatation and adequate release characteristics and hence was suitable for development of a controlled release system . in the present study , in vitro release studies of the floating microspheres were carried out in 0.1 n hydrochloric acid at 37c for a maximum period of 12 hours . at different time intervals , samples were withdrawn and cumulative % drug release was calculated . the percentage drug release of all the formulations is presented in figure 1 . out of 9 formulations tried , the formulation k1 was found to be satisfactory ; since it showed prolonged and complete release with 94.75% at end of 12 h. % drug release of all nine formulations multi unit gastroretentive drug delivery system has additional advantage of absence of dose dumping as in single unit drug delivery . the present investigation described the influence of the drug : polymer ratio on hydrochlorothiazide release . the release and drug entrapment efficiency of the microspheres were affected by the different polymers . it was found that the kollidone sr had a dominant role in the drug release from microspheres rather than acrycoat s 100 and cellulose acetate . and it can be given in hard gelatin capsule form . therefore , it may be concluded that drug loaded floating microspheres in combination with kollidone sr are a suitable drug delivery system for hydrochlorothiazide .

the present investigation described the influence of viscosity and drug : polymer ratio on hydrochlorothiazide release . floating microspheres loaded with hydrochlorothiazide were prepared by emulsion solvent evaporation method . the prepared microspheres were evaluated by micromeritics properties , in vitro drug release , floating ability and drug entrapment efficiency .

the purpose of bone scintigraphy is to portray areas of new bone formation within the skeleton . this is useful in imaging reaction of bone to tumor , fracture , and infection . since approximately half of the administered radioisotope is excreted through renal filtration , abnormalities of the urinary system are also frequently noted during bone scintigraphy . in such cases , to reach an accurate diagnosis , the interpreting physician must first recognize which structures are involved in the uptake and the significance of the uptake . we describe a rare case in which extraosseous bone scan tracer accumulation was noted in a renal calculus . a 60-year - old man , who had difficulty in passing urine for the past 6 months and a complaint of lower back pain presented to our department . on ultrasound imaging , he was found to have an enlarged prostate . transrectal ultrasound - guided biopsy revealed adenocarcinoma of prostate , gleason 's score 3 + 3=6 . his psa was normal ( 1.3 ng / ml ) and serum alkaline phosphatase was elevated 58 u / l ( normal range 30 - 50 u / l ) . a 99 m technitium methylene diphosphonate ( 99 m tc - mdp ) bone scan was performed . the scan [ figures 1 and 2 ] showed mildly increased tracer uptake in lumbar vertebrae and focal accumulation of tracer in lower pole of the left kidney . fusion imaging [ figure 3 ] , using single photon emission computed tomography along with x - ray computed tomography ( spect - ct ) of the lumbar spine was performed to characterize the vertebral tracer uptake . lasix 40 mg was given 45 minutes prior to spect - ct to monitor the renal tracer accumulation . high tracer uptake in a lower pole of the left kidney was found localized in a calculus in the lower calyx of kidney . the ct attenuation factor was 1060 hounsfield unit , compatible with that of a renal calculus . ( a ) anterior and ( b ) posterior views , showing mildly increased tracer uptake in the lumbar vertebrae ( black arrow ) and intense , focal localization of the tracer in the lower pole of left kidney ( red arrows ) . ( a - b ) lateral and ( c - d ) oblique views clearly demonstrate the focal tracer uptake outside the skeletal structures in left kidney ( arrows ) . ( a ) coronal , ( b ) sagittal and ( c ) transaxial ct images ; ( d ) coronal ( e ) sagittal and ( f ) transaxial spect images ; ( g ) coronal , ( h ) sagittal and ( i ) transaxial spect - ct images . the ct attenuation factor was 1060 hounsfield unit , compatible with that of a renal calculus . we concluded this as extra - skeletal bone scintigraphy tracer uptake in a renal calculus . bone scintigraphy is a valuable diagnostic tool in the evaluation of patients with a variety of osseous abnormalities . however , accumulation of bone scan tracer outside the skeleton can pose a difficulty in reporting for a nuclear medicine physician , especially if only planar imaging is performed and the tracer uptake is overlapping or is in close vicinity of the skeleton . localization of bone scan tracer in a renal calculus has been reported in the past and its use in preoperative in vivo localization of the renal calculus has been explored . retention of bone scan tracer on ureteric calculi and bladder calculus has been reported in the past.[35 ] in one of the studies , autoradiography of ureteric calculus demonstrated peripheral tracer distribution within the calculus . accumulation of the radionuclide due to sluggish flow and its absorption onto the crystal surface , within the calculus , were suggested as possible mechanisms of tracer uptake . the other common causes of urinary system localization of the bone scan tracer are dilation of urinary - collecting system , bladder diverticulum , and presence of an ureterostomy bag.[69 ] conditions causing extraskeletal accumulation of bone scan tracer must be kept in mind while reporting a bone scan . our case demonstrates a rare occurrence of extraosseous bone tracer accumulation in a renal calculus . it also highlights important role played by spect - ct in localizing the extraskeletal tracer uptake . spect - ct can be used effectively when an extraskeletal uptake is encountered on planar bone imaging .

extraosseous localization of radioisotope , used in bone scan , in a variety of physiological and pathological conditions is a well - known phenomenon . the causes of extraosseous accumulation of bone - seeking radiotracers should be kept in mind when bone - imaging studies are reviewed to avoid incorrect interpretations . we report an extremely rare occurrence of extraosseous accumulation of bone scintigraphy tracer in a renal calculus , in a patient with adenocarcinoma of prostate , that was demonstrated by single photon emission computed tomography and computed tomography ( spect - ct ) fusion imaging .

functional metabolic imaging of the brain using fluorine-18 fluorodeoxyglucose ( fdg ) positron emission tomography ( pet ) is one of the most useful tools in distinguishing the patient 's symptoms from the various types of dementia by elucidating global and regional deficits in cerebral glucose metabolism . magnetic resonance imaging ( mri ) often plays a role as well , as it is more widely available , and is used to evaluate structural abnormalities within the brain parenchyma . we present a case where hybrid imaging of pet / mri was used to diagnose a patient with semantic dementia ( sd ) , which is one of the lesser known subtypes of frontotemporal lobe dementia ( ftd ) . sd is characterized by a loss of language and verbal skills with late stage behavioral changes . it is associated with predominantly temporal lobe atrophy ( left greater than right ) and is often referred to as temporal variant ftd . a 61-year - old , right - handed male presented with a sudden change in mental status preceded by a significant decline in functionality over the past 2 years . he was previously a highly functional person and worked as an executive for a fortune 500 company . his change in mental status was characterized by several behavioral changes ; including cruelty toward family members and pets , promiscuity , adultery , drug abuse , wild spending habits , and lack of empathy . his family had also noticed a change in his speech patterns in terms of phonation and pronunciation of words . his initial diagnosis was bipolar disorder ; however , he did not respond to mood stabilizing drugs . after losing his job , the mri [ figure 1 ] demonstrated diffuse parenchymal atrophy , which was slightly more extensive in the temporal lobes . there was a lacunar infarct in the right thalamus that was suggestive of vascular dementia . 61-year - old male with change in mental status and decline in function diagnosed with semantic dementia . ( a and b ) the magnetic resonance imaging ( mri ) transaxial views of the t1-weighted and ( c and d ) t2-weighted images with proton density and fluid suppression sequences demonstrate diffuse parenchymal atrophy , slightly more substantial in the temporal lobes ( arrows on a and c ) . these non - specific findings do raise the possibility of frontotemporal dementia ( ftd ) . a thalamic infarct ( arrows on b and d ) , along with subtle white matter abnormalities are also seen , which are suggestive of vascular dementia , though inconsistent with the negative magnetic resonance angiography findings . the images were co - registered with the mri using the institute of electrical and electronics engineers ( ieee ) mutual information algorithm . the resultant pet / mr images [ figure 2 ] demonstrated a pattern of decreased fdg uptake that was predominantly confined to the temporal lobes and was particularly severe in the amygdalae and hippocampi . the decrease in activity was greater on the left side and extended superoposteriorly toward the parietal lobe and wernicke 's area . the other atrophic areas and white matter changes seen on the mri had intact glucose metabolism . the lacunar infarct also had decreased fdg uptake , but that was considered to be an incidental finding . the decreased glucose metabolism affecting only the temporal lobes ( worse on the left side ) with the concordant areas of atrophy on the mri were highly specific for semantic dementia and allowed for a definitive diagnosis to be made . 61-year - old male with change in mental status and decline in function diagnosed with semantic dementia . the fluorine-18 fluorodeoxyglucose ( f-18 fdg ) positron emission tomography ( pet ) of the brain was obtained and coregistered with the t1-weighted sequences of the mri . two separate triangulated cross - sections of the reconstructed images in ( a and d ) axial views , ( b and e ) coronal views , and ( c and f ) sagittal dimensions show significantly reduced uptake corresponding to atrophy in the temporal lobes ( arrows on a ) , involving the amygdalae ( arrows on b ) , hippocampi ( arrows on e ) , and wernicke 's area ( arrow on c ) . the function is well preserved in the remaining areas of global atrophic change and white matter changes . there is also reduced activity in the location of the suspected right thalamic infract ( arrow d ) . although each type of dementia has its own constellation of symptoms , there is significant overlap and most patients present with features of several different psychiatric and neurologic disorders . the majority of patients present with some type of memory loss with a variety of non - specific behavioral changes . anatomic imaging is often not useful , other than to exclude physical causes such as stroke or hydrocephalus . there may be subtle clues to a diagnosis , but nothing definitive . functional imaging provided by fdg pet evaluation of brain glucose metabolism alzheimer 's dementia ( ad ) is characterized by decreased glucose metabolism in the temporal and parietal lobes with sparing of the frontal lobes . ftd , as the name suggests , demonstrates decreased activity in the frontal and temporal lobes with sparing of the parietal lobes . dementia with lewy bodies ( dlb ) has pattern of decreased activity similar to ad , but also demonstrates decreased activity in the occipital lobe . however , many early stages of dementia may have atypical or variable appearances on fdg pet . for example , semantic dementia has involvement confined to the temporal lobe , but the deficits are often not as striking as in the other types of dementia on fdg pet . on mri , the aforementioned types of dementia may show global atrophy , with more extensive changes in the involved lobes ( such as more frontal lobe atrophy in ftd ) . however , these structural changes often occur late in the disease progression and can be non - specific . additionally , there is no typical structural abnormality in dlb . often at times , the fdg pet will show metabolic deficits before atrophic changes become apparent on mri . in this case , we were able to combine metabolic deficits with the anatomic information provided by mri . this allowed us to corroborate the decreased activity confined to the temporal lobe with specific structures or areas within the brain that were involved . the amygdale , hippocampi , and wernicke 's area all showed focal decreases in activity compared with the overall reduction of radiotracer activity in the temporal lobes . the fdg pet , on the other hand , showed that the decreased activity was greater on the left side , which is classic for semantic dementia , whereas the atrophy on the mri seemed relatively symmetric . since the affected areas of the brain are involved in empathy ( amygdala ) , meaningful word usage ( wernicke 's area ) , memory ( hippocampus ) , and conceptual knowledge ( amygdala and hippocampus interaction ) ; the patient 's symptoms could be easily explained . this case demonstrates an example of the value of combined pet - mri in clinical practice . co - registration of images provides essential information that is needed to make a diagnosis in challenging cases . thus , clinical symptoms can be related to lesions in specific parts of the brain .

we report a case of a 61-year - old male who presented with a sudden change in mental status . from a psychiatric standpoint , his symptoms were consistent with a bipolar disorder . a neurology consult raised suspicion for vascular dementia , given the sudden onset of symptoms ; however , the magnetic resonance angiography ( mra ) was unremarkable . the magnetic resonance imaging ( mri ) had findings that were suggestive of both vascular and frontotemporal lobe dementia based on parenchymal atrophy and a lacunar infarct near the thalamus . however , by co - registering the magnetic resonance images with a subsequent fluorine-18 fluorodeoxyglucose positron emission tomography ( f-18 fdg pet ) , and combining the functional data with the anatomic appearance , the diagnosis was narrowed to semantic dementia , which is one of the lesser known subtypes of frontotemporal lobe dementia ( ftd ) .

in our model , each particle consists of a core sphere with four tetrahedrally oriented arms ( see fig . the central sphere and the arms are modeled as interpenetrating hard spheres with diameter , with the centre of each arm located a distance l from the centre of the core . on the surface of each arm the patch is modeled , via a standard kern - frenkel potential , as a square - well type attraction of depth : two particles are either bound or unbound , with no intermediate energy levels . the opening angle of the patch is given by cos = 0.95 , and the maximum interaction range = 0.251. this choice ensures that each patch can form a bond with only a single other patch . furthermore , in order to model arm flexibility , each arm can freely rotate around the core sphere within a maximum angle from its ideal ( tetrahedral ) position . note that there are no hard - core interactions within a particle : spheres belonging to the same tetramer can overlap . each mc simulation included translation moves , rotation moves rotating a full tetramer , rotation moves rotating only the core sphere , and rotation moves that rotate a single arm around the core . additionally , we added volume moves for isobaric simulations , and particle insertion and deletion moves for grand - canonical successive umbrella sampling ( sus ) simulations . to detect ll phase separation , we used sus simulations , generating the relative free energy as a function of the density . to calculate the phase diagrams in fig . 4 , and the crystallization lines in figs . 2 and 3 for the liquid phases , we used a high temperature fluid as a reference state , where we obtained the helmholtz free energy f by combining the chemical potential ( evaluated from a sus simulation ) and the pressure p at the same density ( taken from an npt mc simulation ) , using : ( 1)ffn=p , where n is the number of particles . we then used thermodynamic integration by integrating the temperature along an isochore : ( 2)2f(,t2)=1f(,t1)+12du(,t ) , with u( , t ) the average potential energy per particle , = 1/kbt and kb boltzmann s constant . typically , at sufficiently low temperatures , the energy as a function of temperature takes the form ( 3)u=2+cexp(2 ) , where 2 is the ground - state energy ( where each particle has four bonds ) and c is a ( density - dependent ) constant . this allows for straightforward extrapolation of the free energies to arbitrarily low temperatures after the regime in eq . this regime is accessible in our simulations for all cases where the fluid does not crystallize at low t ( i.e. cos 0.9 ) . system sizes for the sus simulations were chosen such that near the ll transition the system contained n 150 particles . other free - energy calculations were performed with similar or larger n. the investigated crystal structures were diamond and bcc ( corresponding to ice ic and ice vii in water , respectively ) . both are fully bonded structures and as such have the ( same ) lowest possible potential energy . depending on cos and l , there will be a variety of other fully bonded crystal structures . however , the structures commensurate with an ideal tetrahedral geometry will always have the highest entropy and hence will be more stable at the densities where they are accessible . thus , the only crystals which might compete with the ll phase separation are diamond and bcc . at high density , i.e. beyond the bcc density , the stable crystalline phases will be controlled by a competition between packing , energy , and entropy , but as these phases will not change the stability of the ll phase transition , they are outside of the scope of this letter . similarly , we do not expect these crystal phases to affect the phase diagrams in fig . 4 , with the possible exception of the ( dashed ) high - density liquid - bcc lines in panels ( c ) and ( d ) . to determine free energies for the crystal phases , we used an einstein crystal approach , for each t where a phase coexistence was calculated . subsequently , using npt mc simulations , we employed thermodynamic integration along the density at constant temperature : ( 4)f(,t)=f(ref , t)+refd()p2 , where ref is the density where the reference free energy was calculated . s4 in the si for examples ) . to determine whether spontaneous crystallization occured in our sus simulations , we used a bond - order parameter to find the largest crystalline cluster in the system . first , we determine the neighbors of each particle using a solid - angle based nearest - neighbor method . we then calculate for each particle the complex vector ql , the expansion of their environment in terms of spherical harmonics ylm , with l the order of the symmetry of the crystal , and l m l : ( 5)qlm(i)=1nb(i)j=1nbylm(r^ij ) . here , nb is the number of neighbors of particle i , and r^ij is the normalized vector connecting particle i to particle j. for the purpose of finding crystalline clusters , two particles are considered bonded when their environments are sufficiently similar . to determine this , we calculate : ( 6)dl(i , j)=re(ql(i)ql(j)ql(i)ql(j) ) . to detect bcc clusters , we choose l = 6 , consider two particles bonded if dl(i , j ) > 0.6 , and label any particle that has at least 5 bonds as a crystalline particle . for diamond , two particles are considered bonded if either dl(i , j ) < 0.87 or 0.3 < dl(i , j ) < 0.1 , and only particles with 4 bonds are considered crystalline . systems were considered to have crystallized spontaneously when more than 10% of the system was crystalline . note that although the q6 based order parameter is sensitive to multiple crystal structures , visual inspection of the detected clusters consistently showed a bcc structure in all cases .

one of the most controversial hypotheses for explaining the origin of the thermodynamic anomalies characterizing liquid water postulates the presence of a metastable second - order liquid - liquid critical point [ 1 ] located in the no - man s land [ 2 ] . in this scenario , two liquids with distinct local structure emerge near the critical temperature . unfortunately , since spontaneous crystallization is rapid in this region , experimental support for this hypothesis relies on significant extrapolations , either from the metastable liquid or from amorphous solid water [ 3 , 4 ] . although the liquid - liquid transition is expected to feature in many tetrahedrally coordinated liquids , including silicon [ 5 ] , carbon [ 6 ] and silica , even numerical studies of atomic and molecular models have been unable to conclusively prove the existence of this transition . here we provide such evidence for a model in which it is possible to continuously tune the softness of the interparticle interaction and the flexibility of the bonds , the key ingredients controlling the existence of the critical point . we show that conditions exist where the full coexistence is thermodynamically stable with respect to crystallization . our work offers a basis for designing colloidal analogues of water exhibiting liquid - liquid transitions in equilibrium , opening the way for experimental confirmation of the original hypothesis .

the success of root canal therapy is dependent on understanding the anatomy of root and root canal morphology.1,2 awareness and understanding of the presence of unusual external and internal root canal morphology largely contributes to the successful outcome of the root canal treatment . in literature , description of the mandibular first premolar is typically of a single - rooted tooth.3,4 two - rooted , three - rooted , and four - rooted varieties have also been reported , but are rare.5,6 the root frequently has developmental depressions or grooves on both the mesial and distal surfaces . according to slowey , the mandibular premolars may present the greater difficulty of all teeth for a successful endodontic treatment.7 a study at the university of washington in 1955 assessed the failure rate of non - surgical root canal therapy ( nsrct ) in all teeth . numerous endodontic failures after a routine treatment and flare - ups during the course of nsrct are cited as evidence . it could be because of variations in root canal morphology and difficult access to additional canal systems.8 this case report presents a successful , non - surgical management of mandibular left second premolar with three roots and root canals and a first premolar with two roots using a cone beam computed tomography ( cbct ) . a 31-year - old male patient was reported to the department of conservative dentistry and endodontics , mnr dental college and hospital with a chief complaint of pain and pus discharge in the lower left back tooth region since 3 months . , there was a gingival inflammation with recession in relation to tooth numbers 34 , 35 , 36 . electric pulp testing and thermal testing of the teeth indicated non vitality of 34 , 35 , and 36 . a confirmatory diagnosis of acute apical abscess in relation to 34 , 35 , and 36 was established and endodontic therapy was planned . the mesiodistal width of the crown is lesser than mesiodistal diameter of the root and for further confirmation a cbct ( gentex ) , was planned . cbct with a 3d reconstruction confirmed a three rooted 34 and two rooted 35 ( figure 1b - d ) . ( a ) pre - operative radiograph showing first and second premolar and first molar . the area was anaesthetized using 2% lignocaine with 1:80,000 adrenaline ( lignox ) and isolated with a rubber dam . an access cavity was prepared with a modification that it had a cut at the buccoproximal angle from the entrance of the buccal canals to the cavosurface angle , so that it is results in a t - shaped outline ( figure 2a ) . a working length was determined with an apex locator ( root - zx ) ( figure 2b ) . with crown down technique , cleaning and shaping were performed with twisted file and protaper rotary instruments ( dentsply mailfilter ) . abundant irrigation with 3% sodium hypochlorite solution is done . biomechanical preparation is done up to f2 . before obturation irrigation with 17% , edta and saline are done . obturation is done with gutta - percha and resin sealer ( ah plus , dentsply ) by cold lateral condensation ( figure 2c ) . the coronal access was restored with resin composite ( 3 m espe ) ( figure 2d ) . successful and predictable endodontic treatment requires knowledge of biology , root canal anatomy , and careful radiographic evaluation in order to determine number of roots and root canals . preoperative parallel radiographs , as well as mesial or distal angled radiographs , can help to determine number of roots . the diagnosis and management of extra roots or root canals in mandibular premolars pose an endodontic challenge . failing to locate and obturating a root canal is the major cause of failure in endodontic therapy . hoen and pink found 42% incidence of missed roots or canals in the teeth that needed retreatment.9 according to cleghorn , the incidence of three rooted mandibular first premolars is 0.2%.10 hence , it is import that all the canals be located and treated during the course of nonsurgical endodontic therapy . rodig and hulsmann have reported a case of mandibular second premolar with three separate roots and root canals diagnosed using intraoral periapical radiographs.2 wong and al - fouzan have published cases of mandibular second premolars with four canals.11,12 tzanetakis et al . have reported endodontic management of mandibular second premolar with four root canals diagnosed with the aid of operating microscope.13 it has been established that a root with a tapering canal and a single foramen is the exception rather than the rule . serman and hasselgren ( 1992 ) reported a high incidence of multiple roots ( 18.1% ) and root canals in mandibular premolar teeth in a series of radiographic surveys with mandibular first premolars involved in 15.7% of patients and mandibular second premolars in 7% of patients.14 studies by lu et al . are similar to slowey suggestions that mandibular premolars are the most difficult to treat endodontically and also the apical configuration of these teeth was found to be complex.15 thus , a careful understanding and diagnosis of canal anatomy is of utmost importance for successful management of such cases . accurate preoperative radiographs of good quality along with an occlusal view , into the access opening and down the chamber of a mandibular premolar tooth , rarely shows any chamber floor , even when a suspected bifurcation of the canal is seen on the radiograph . the surgical operating microscope sometimes aids in canal visualization of a canal system branching off the main canal . a fine , curved stainless steel file with a good tactile sense is the best guide to the detection of the accessory canals.16 a modification in the access cavity preparation is often needed for unhiding the additional orifices of the root canals or the orifices of the extra roots for a better instrumentation . when present the roots are usually mesiobuccal , distobuccal , and a lingual root . at least two radiographs , with the second radiograph angulated from 15 to 20 either mesial or distal from the horizontal long axis of the root , are required to reliably diagnose more than one root or root canal system in premolar teeth . a sudden narrowing of the main canal on a parallel radiograph was a good criterion to judge root canal multiplicity.17 however , martinez - lozano et al . recommend up to 40 mesial angulation from horizontal as more reliable in identifying the extra canals.18 deviation of the x - ray angle from the vertical axis of 15 to 30 was effective only in the mandibular first premolar in helping to visualize canal anatomy of premolar teeth . dyes , fiber - optic transillumination , magnifying loupes , and sodium hypochlorite bubbling in the extra canals help in locating additional canals . with the advent of advanced imaging techniques , an understanding of complex anatomies cbct is better of digital radiographic techniques in identifying multiple root canal systems in the mandibular incisor , mandibular first premolar , and maxillary first molar teeth.19 management of teeth with morphological variations presents a challenge , which requires proper instruments and the knowledge to use the instruments effectively . advanced imaging techniques like cbct are valuable tools in diagnosing and managing cases , which deviate from the regular pattern . the present case report emphasizes the need to understand , interpret , and manage a three rooted mandibular first premolar with three roots which has been successfully managed using cbct .

understanding the morphological anatomy of the root and root canal systems of the teeth increases the success rate of endodontic therapy . advanced diagnostic imaging techniques like cone beam computed tomography ( cbct ) are an essential aid in understanding the anatomy of teeth especially in mandibular premolars . most commonly mandibular first and second premolars have a single root and a single canal . however , multiple root and canals have also been reported . the present case report discusses endodontic management of a three rooted mandibular first premolar using cbct .

in february 2010 , a 39-year - old man fractured both bones of the forearm after his arm was caught in a conveyor belt ; he underwent a surgery at another hospital . an intramedullary forearm rod ( acumed , hillsboro , or , usa ) nineteen months after surgery , an attempt was made to remove the implant ; it failed because the threaded portion of the nail remover was broken while being connected to the nail ( fig . two years after the failed surgery , the patient visited us with complaints of occurrence of left elbow pain , without having any new trauma . a partial defect of the triceps tendon with severe pain and tenderness around the scar of nail insertion was noted . ultrasonography revealed partial rupture of the triceps tendon , and bursitis around the tender area . based on these observations , the authors planned to remove the nail and repair the tendon . surgery was performed under general anesthesia , with the patient in the supine position ; a tourniquet applied to the affected area . the forearm was placed on the patient 's chest , with the shoulder joint and elbow joint each flexed at 90. a longitudinal skin incision exposed the hole of the nail insertion and the interlocking screws . the inlet site of triceps brachii muscle was thinned not torn ; it was not possible to grip since it was already covered by the bone . we removed the bone at the inlet site and created another bony window using an osteotome , to expose the interlocking screw holes . we inserted an impactor in the middle interlocking hole , after which we tapped the impactor towards the proximal side . the nail moved one inter - interlocking hole distance , and its end point passed through the triceps brachii tendon . we gripped the end point of the nail by a vise grip and used a hammer to remove it ; however , the proximal part of the nail was damaged , and the vise grip and nail were separated ( fig . finally , we hit the distal most part of the interlocking hole , and moved the nail to a two inter - interlocking hole distance . based on the authors ' experience , we propose a surgical technique that can easily remove the nail , and minimize size of the bony window and damage to the triceps brachii . the distal incision is approximately the size of 2 inter - interlocking holes , and the proximal incision is about 1 cm , big enough to pass the nail ( fig . 4 ) . only needs one inter - interlocking hole length of the bony window . it needs to be placed on the proximal 2 interlocking holes , and not on the distal hole ( fig . an impactor is inserted on the distal hole , and tapped proximally by the mallet ( fig . 6a ) . when the hole is moved to proximal part of the bony window ( fig . 6b ) , a new interlocking screw hole appears in the distal part of the window ( fig . the impactor is then laid on the new distal interlocking hole and tapped again ( fig . , the triceps brachii tendon can be carefully monitored , without being impacted by the nail in any way . the nail is then exposed enough to be gripped firmly ( figs . 3 and 6e ) . after the nail removal , the triceps brachii tendon is sutured and the bony window is covered , using the bone that was removed to make the window . the distal incision is approximately the size of 2 inter - interlocking holes , and the proximal incision is about 1 cm , big enough to pass the nail ( fig . it needs to be placed on the proximal 2 interlocking holes , and not on the distal hole ( fig . in the bony window , an impactor is inserted on the distal hole , and tapped proximally by the mallet ( fig . 6a ) . when the hole is moved to proximal part of the bony window ( fig . 6b ) , a new interlocking screw hole appears in the distal part of the window ( fig . 6c ) . the impactor is then laid on the new distal interlocking hole and tapped again ( fig . , the triceps brachii tendon can be carefully monitored , without being impacted by the nail in any way . the nail is then exposed enough to be gripped firmly ( figs . 3 and 6e ) . after the nail removal , the triceps brachii tendon is sutured and the bony window is covered , using the bone that was removed to make the window . intramedullary nailing can be used to treat fractures with minimal skin incision . owing to its reliable biomechanical results , it is widely used in cases of long bone fracture . however , its direct placement into the bone can sometimes cause difficulty in handling . a hooked - shaped , modified guide pin was used when the nail 's middle portion had broken . levy et al.2 ) reported a method of removing the distal piece of the broken nail , using another nail less than 1 mm . georgiadis et al.3 ) reported on the management of failed proximal piece of the nail removal in the leg . despite reports of such related cases , there were no case reports in the existing literature about failure of retrieval of an ulnar intramedullary nail . when the extraction device is broken during removal of the ulna nail , only a bony window the size of 2 inter - interlocking holes at the most proximal part of the nail can be used to remove the nail with minimal damage of the triceps brachii tendon and soft tissue . in spite of the simplicity and usefulness of this method , care should be taken when making the bony window , because there is potential risk of a fracture around the olecranon , especially in osteoporotic old patients .

methods about removal of intramedullary nail in complicated cases were reported in some literatures but there are no reports about nail removal in the ulna . the authors would like to report such a case and the technique . we removed bone of the inlet site and created another bony window using an osteotome to expose the interlocking screw holes . only a bony window the size of 2 inter - interlocking holes at the most proximal part of the nail can be used to remove the nail with minimal damage of the triceps brachii tendon and soft tissue .

bow hunter 's syndrome ( bhs ) is caused by the compression of the dominant vertebral artery ( va ) against a fibrous band or osseous prominence by rotational head movement2,6,10 ) , leading to ischemic insult in the vertebrobasilar territory8,14 ) . bhs presents as recurrent attacks of paroxysmal vertigo , nystagmus , and ataxia caused by head rotation5,8,10 ) . due to the rarity of this pathology recently , we encountered 2 cases , which we present herein along with our surgical approach . in these 2 cases , we were able to achieve successful decompression of the va ; the two patients recovered completely without further clinical symptoms . a 50-year - old woman had been experiencing paroxysmal vertigo attacks for a 10 month period prior to visiting our institute . the patient 's vertigo was aggravated when she turned her head to the left side . scans , we observed no definitive abnormal findings except for hypoplastic left va in the neutral position ( fig . 2a ) , but complete occlusion of right va was found at atlanto - axial level when the patient turned her head to the left side ( fig . we decided on a surgical decompression of the left va at the cross transverse foramen of the first cervix as the surgical approach . we placed an adhesive , fibrous bandage between the left va and the transverse foramen . during the surgical procedure , after surgery , the patient 's symptoms improved , and her neck three - dimensional angiography ct scans demonstrated complete decompression of the right vertebral artery ( fig . 3 , 4 ) . a 42-year old woman reported severe vertigo , dizziness , right upper extremity tingling sensations and aggravated syncope when she turned her head to the right . upon otolaryngological examination , she presented right beating nystagmus when her head was rotated to the right in the sitting or supine position . there were no abnormal findings except for hypoplasia of the posteroinferior cerebellar artery termination of the left va on magnetic resonance angiography . however , dynamic cerebroangiography showed no steno - occlusive lesions of left va in the neutral position ( fig . 5a ) , but an occlusion of the left va was observed at the c1 - 2 level from right head rotation ( fig . we selected a surgical approach and found an adhesion between the left va and transverse foramen . a 50-year - old woman had been experiencing paroxysmal vertigo attacks for a 10 month period prior to visiting our institute . the patient 's vertigo was aggravated when she turned her head to the left side . scans , we observed no definitive abnormal findings except for hypoplastic left va in the neutral position ( fig . 2a ) , but complete occlusion of right va was found at atlanto - axial level when the patient turned her head to the left side ( fig . we decided on a surgical decompression of the left va at the cross transverse foramen of the first cervix as the surgical approach . we placed an adhesive , fibrous bandage between the left va and the transverse foramen . during the surgical procedure , after surgery , the patient 's symptoms improved , and her neck three - dimensional angiography ct scans demonstrated complete decompression of the right vertebral artery ( fig . 3 , 4 ) . a 42-year old woman reported severe vertigo , dizziness , right upper extremity tingling sensations and aggravated syncope when she turned her head to the right . upon otolaryngological examination , she presented right beating nystagmus when her head was rotated to the right in the sitting or supine position . there were no abnormal findings except for hypoplasia of the posteroinferior cerebellar artery termination of the left va on magnetic resonance angiography . no significant changes were observed with neck rotational positions . however , dynamic cerebroangiography showed no steno - occlusive lesions of left va in the neutral position ( fig . 5a ) , but an occlusion of the left va was observed at the c1 - 2 level from right head rotation ( fig . we selected a surgical approach and found an adhesion between the left va and transverse foramen . bhs is syndrome characterized by symptoms such as dizziness , vertigo , and blurred vision when the patient rotates his neck . bhs is defined as symptomatic vertebrobasilar insufficiency by a mechanical occlusion of the vertebral artery during head rotation9 ) . however , because of the collateral blood flow through the contralateral va and the circle of willis , va occlusion does not cause symptoms in most individual cases11 ) . thus , symptomatic bhs is rare . because of its rarity , no large - scale established protocols exist for its research , treatment , or diagnosis . the compressive occlusion of the va is occurs due to a variety of reasons , including the fibrous band tethering of the va at the transverse foramina of the c1-c2 junction , as in our cases , and at the point of dural penetration , which is located above the atlantooccipital membrane . a pathognomonic finding of bhs is the improvement of symptoms when the patient is in a neutral position , even after he claims to have dizziness or blackout when he turns his head to one side . when bhs is suspicious , considerable authors used digital subtraction angiography as the diagnostic modality1 ) . in our cases , clinical symptoms were aggravated when patients turned their head to one side ; symptoms were improved when the patients ' heads returned to a neutral position . furthermore , we conducted dynamic angiography to confirm occlusive va lesions toward a diagnosis of bhs . because of the rarity of this pathology , there are no long term follow - up studies ; only prospective studies exist for bhs treatment . thus , there is no guideline to support the decision to proceed medically or operatively . because of post - operative complications and the impact on quality of life , some authors have suggested medical treatment ( anticoagulation , neck collar applied not to rotate the head , etc.12 ) . however , other patients with bhs who were treated conservatively with medication required surgery because of repeated , aggravated symptoms ; after surgery , these patients showed clinical improvement3 ) . patients who had vascular decompression for bhs at the atlanto - axial level had shown signs of improvement in several case reports1,4,7,13 ) . as mentioned above , there is no definitive guideline for the diagnosis and treatment of bhs because of its rarity . the surgical decompression of mechanical va compressions constitutes an appropriate treatment with a good prognosis .

bow hunter 's syndrome ( bhs ) is rare cause of vertebrobasilar insufficiency that arises from mechanical compression of the vertebral artery by head rotation . there is no standardized diagnostic regimen or treatment of bhs . recently , we experienced 2 cases resisted continues medication and treated by surgical approach . in both cases , there were no complications after surgery and there were improvements in clinical symptoms . thus , we describe our cases with surgical decompression with a review of the relevant medical literature .

malignant hematologic disorders ( multiple myeloma , myelodysplasia , chronic lymphocytic leukemia , and hodgkin 's and non - hodgkin 's lymphoma ) and idiopathic aplastic anemia that occur in the population with an incidence of 0.5 - 5/100,000 increase the surgical operative risk due to coagulation defects , changes of blood viscosity , immunosuppression , and bone marrow insufficiency ( 1 ) . pancytopenia associated with idiopathic aplastic anemia may pose an increased risk for postoperative bleeding and infection ( 2 ) . here , we report a patient with severe aortic valve insufficiency undergoing bioprosthetic aortic valve replacement who suffered from idiopathic aplastic anemia . a 66-yr - old man was admitted to the hospital because of shortness of breath . his dyspnea was classified by the new york heart association ( nyha ) as functional class iii . the patient 's history included treatment for severe aplastic anemia with anti - thymocyte globulin and prednisone for 5 yr prior to admission . echocardiography revealed reduced left ventricular function and severe aortic valve regurgitation ( grade iv ) with left ventricular end diastolic dimension measuring 87 mm . the presence of severe dyspnea and echocardiographically documented severe aortic valve insufficiency led us to schedule a surgery for elective aortic valve replacement . on admission , laboratory testing showed leukocytopenia ( white blood cells 1,900/l ) , anemia ( hemoglobin 6.7 mm / l ) , and thrombocytopenia ( platelets 34,000/l ) . the differential blood count revealed 42.9% neutrophils ( 50 - 70% ) , 42.3% lymphocytes ( 25 - 40% ) , 6.9% monocytes ( 2 - 8% ) , and 4.3% eosinophils ( 2 - 4% ) . preoperative preparation included two weeks of granulocyte colony - stimulating factor ( neupogen 300 g , amgen , subcutaneously three times a week ) , transfusion of four units of packed red blood cells ( rbcs ) , and ten units of platelet concentrations ( pcs ) one day before the surgical procedure resulting in a hemoglobin level of 9.8 mm / l , a leukocyte level of 10,300/l , and a platelet level of 120,000/l preoperatively . the patient received aortic valve replacement with a 21-mm bioprosthetic aortic valve ( carpentier - edwards , edwards lifesciences , irvine , ca , u.s.a . ) by a standard median sternotomy ; 2 milrione units of aprotinin were added to the cardiopulmonary bypass circuit priming solution . on the second day after surgery , atrial fibrillation deveolped and was successfully converted with intravenous amiodarone . antibiotic prophylaxis was given using ceftriaxon ( rocephin , roche , basel , swiss ) 2 g intravenously over 6 days . the patient was discharged from the intensive care unit 4 days after surgery and was discharged from the hospital postoperative on day 11 with a leukocyte count 4,300/l , hemoglobin of 6.2 mm / l , and a platelet count of 62,000/l . after the surgery , the patient received 5 units of rbcs and 20 units of pcs until discharge . perioperative laboratory findings are summarized in table 1 . during the 6 months of follow - up , the patient did well with a functional class of nyha class i. the chest radiography at 3 months post surgery showed a decreased cardiac size . according to the definition of the severity of aplastic anemia ( 5 ) , the patient 's aplastic anemia could be categorized as non - severe aplastic anemia . regardless of the severity of aplastic anemia , ( 1 ) , two questions have to be considered when cardiac surgery is indicated in patients with a hematologic disorder causing pancytopenia . given the increased operative risk and the potential benefit with regard to the life expectancy and quality of life , aggressive surgical treatment has to be compared with conservative treatment and the natural course of both , the hematologic disorder and the cardiac disease . our patient suffered from severe dyspnea on exertion ; the patient had stable idiopathic aplastic anemia and was under hematological supervision . progressive deterioration of ventricular function was documented on serial echocardiographic examinations . both symptomatic aortic regurgitation and impaired left ventricular function led us to the decision to perform aortic valve replacement for this patient . another important issue for this specific subset of patients is perioperative management to decrease morbidity and mortality ( 1 ) . potential complications are caused by a decreased number or impaired function of blood cells ; this condition is aggravated by the cell damaging properties of extracorporeal circulation . in addition to meticulous surgical hemostasis , substitution of various blood products is important to reduce the risk of bleeding complications . total amount of the blood product transfused to this patient is regarded to be acceptable considering the higher risk of bleeding in these specific subset of patients . aprotinin has been shown to decrease blood loss and reduce the use of blood products by at least 30% , in open heart surgery ( 4 ) . thoracic drainage in our patient was 785 ml , which was similar to that of other patients who required cardiac surgery with a variety of malignant hematological disorders ( 1 , 3 ) . another important aspect of perioperative care in these patients is the increased risk for infections . it is of great importance to perform surgery in aseptic conditions and to avoid transmission of pathogenic microorganisms during the perioperative period . the patient received warfarin sodium 2 days after surgery , and inr was maintained between 1.5 to 2.0 . follow up , we have noticed neither thrombotic nor hemorrhagic complications related to the anticoagulation therapy . ( 3 ) , cardiac surgery with extracorporeal circulation is feasible in patients with idopathic aplastic anemia , and it was not associated with excessive complications that might be expected in a patient with this disorder .

major surgery in a patient with pancytopenia might be associated with increased surgical risks , especially for bleeding and infection . a 66-yr - old man was admitted to the hospital due to shortness of breath . his dyspnea was classified by the new york heart association ( nyha ) as functional class iii . prior to admission , he had a 5-yr history of medical management for idiopathic aplastic anemia . the severity of aplastic anemia of the patient was graded as non - severe aplastic anemia . echocardiography revealed reduced left ventricular function and severe aortic valve regurgitation ( grade iv ) with left ventricular end diastolic dimension measuring 87 mm . because of dyspnea and echocardiographically documented aortic valve insufficiency , the patient underwent elective aortic valve replacement . although extracorporeal circulation for valve operations might be associated with aggravation of impaired blood cell function , the patient recovered from surgery uneventfully . here , we report a successful cardiac surgery with extracorporeal cardiopulmonary bypass in a patient with severe aortic valve insufficiency and concomitant idiopathic aplastic anemia .

opipramol is an atypical anxiolytic and antidepressant drug which has been found to be effective in depressive disorder . although it was developed by schindler and blattner in 1961 , its use was limited and recently it has regained popularity among psychiatrists all over for the treatment of somatoform and depressive disorders . structurally its nucleus is similar to that of tricyclic antidepressant imipramine and the attached side chain is identical to that of perphenazine . although it is structurally similar to tricyclic antidepressants , it does not inhibit the neuronal uptake of norepinephrine and/or serotonin and is a sigma - receptor agonist , primarily at the sigma-1 receptor subtype , but also at the sigma-2 subtype with lower affinity . sigma receptor agonist opipramol is not presumed to cause affective switch because of its relative sparing of monoamine receptors . hereby , we describe a case of opipramol - induced mania in a patient with bipolar depression . a 39-yr - old male was brought to our opd with 4 weeks history of talking excessively even to unfamiliar people , being irritable to others , overspending , singing , dancing and reduced need for sleep . it was reported that he had a manic episode with psychotic symptoms 15 years back and was on lithium prophylaxis till 5 years ago . four months ago , the patient consulted a psychiatrist with history of excessive sadness , inability to sleep , easy fatiquability , anhedonia , not being able to carry out his job and reduced libido , and was diagnosed to have moderate depressive episode and was restarted on lithium 900 mg / day . two months ago , as patient did not improve on lithium monotherapy with serum lithium level of 0.7 meq / litre , opipramol 50 mg / day was added along with lithium . and after 1 month on opipramol treatment patient was brought to us with the current symptoms . patient 's investigations showed serum lithium level of 0.7 meq / litre and thyroid function was normal . on mental status examination patient was diagnosed as a case of bipolar affective disorder , current episode being treatment emergent manic switch due to opipramol as per the international society for bipolar disorders ( isbd ) criteria and patient was admitted . opipramol was stopped and patient was continued on lithium 900 mg / day and risperidone titrated up to 4 mg / day . his manic symptoms started resolving by second week and remitted by fourth week and the patient was discharged . the total manic score on young 's mania rating scale was 39 at the time of admission and it dropped to 28 , 17 and 6 at the end of first , second and fourth week of treatment , respectively . although being effective , almost all the antidepressants carry a risk of mania / hypomania in bipolar affective disorder . treatment - emergent affective switch ( teas ) is not well defined and according to the international society for bipolar disorders ( isbd ) 2009 criteria , switch can be called as definite treatment emergent manic switch if : it occurs within a window period of 8 weeks from intervention , full syndromic hypomanic , manic , mixed symptoms emerge andif symptoms last for at least 2 consecutive days with daily occurrence of symptomatic periods lasting more than 50% of time each day . it occurs within a window period of 8 weeks from intervention , full syndromic hypomanic , manic , mixed symptoms emerge and if symptoms last for at least 2 consecutive days with daily occurrence of symptomatic periods lasting more than 50% of time each day . in the largest multicentre trial of antidepressants in bipolar depression step bd , when patients followed for up to 2 years , transition from depression directly to manic , hypomanic or mixed states was observed in 21% of individuals prospectively observed for a single episode . tricyclic antidepressants ( tcas ) have consistently been associated with a high risk of teas compared to other antidepressants ; incidence rates ranging from 9% to 69% . the question whether concomitant use of mood stabilizers would reduce the switch inducing property of antidepressants is unanswered and wide variation in rates of teas observed in studies is often attributed to concomitant administration of mood stabilizers . studies show that when mood stabilizers are combined with tcas risk of switching to mania is significantly reduced . when used along with mood stabilizers very low switch rates ranging from 0% to 3.7% , manic symptoms emerged within 4 weeks of opipramol treatment even though he was on lithium and serum lithium level was optimal . the dose of opipramol in our case was 50 mg / day which indicate that even very low dose of opipramol has propensity to cause switch to mania . it does not have inhibitory action on reuptake of norepinephrine or serotonin and dopamine unlike other antidepressants . opipramol also blocks histamine , serotonin , dopamine and alpha-1 adrenergic receptors , on the basis of which switch due to opipramol can not be explained . ssris , tcas and norepinephrine - dopamine reuptake inhibitor bupropion which are reported to cause switch also have sigma receptor agonism and only factor which is shared between these drugs and opipramol is the affinity for sigma receptors . in animal models , sigma-1 receptor mediates stimulant and appetitive properties of cocaine which is similar to hypomanic symptoms and sigma-1 receptor antagonists block the hyperlocomotion and appetitive effect of cocaine . hence agonistic action on sigma receptor itself may be postulated to cause behavioral activation and manic switch in case of opipramol , though this correlation is yet to be understood in detail . in summarisation , the above - mentioned case of bipolar depression who developed treatment emergent manic switch due to opipramol while on concomitant treatment with lithium remitted by fourth week of opipramol discontinuation . sigma-1 receptor agonism of opipramol may be hypothesized as the basis of manic switch due to opipramol . this is the first case of opipramol - induced manic switch published in the literature and further studies are essential to confirm our view .

antidepressants have propensity to induce manic switch in patients with bipolar disorder . opipramol is an atypical anxiolytic and antidepressant drug which predominantly acts on sigma receptors . although structurally resembles tricyclic antidepressant imipramine it does not have inhibitory action on the reuptake of norepinephrine / serotonin and hence it is not presumed to cause manic switch in bipolar depression . here , we describe a case of mania induced by opipramol , in a patient with bipolar affective disorder who was treated for moderate depressive episode with lithium and opipramol and we discuss neurochemical hypothesis of opipramol - induced mania .

in october 2013 , university of north carolina hospitals , an 853-bed facility , implemented a new hand hygiene program ( clean in , clean out ; http://news.unchealthcare.org/empnews/handhygiene ) in all inpatient areas , after a successful pilot implementation of the program in the pediatric intensive care unit ( 2 ) . key features were that the focus for observation was simply on cleaning hands upon entering and leaving patient rooms and that all healthcare personnel ( including physicians , advanced practice providers , nurses , nursing assistants , hospital unit coordinators , housekeeping , radiology , occupational / physical / recreational therapists , nutrition and food services staff , phlebotomists , and respiratory therapists ) were asked to make observations and provide immediate feedback to each other ( 3 ) . previously , infection preventionists and designated nursing staff on each inpatient unit performed covert observations of hand hygiene compliance according to centers for disease control and prevention ( cdc ; atlanta , ga , usa ) indications for hand hygiene ( 1 ) , and compliance reports by location were disseminated quarterly . comprehensive surveillance for device - associated and non device - associated hai was assessed by 4 infection preventionists according to cdc national healthcare safety network case definitions and included all hospital locations and all infections . we compared hand hygiene compliance data from the last quarter of the covert observations by infection preventionists and designated nursing staff to compliance data from the first month of the new program by using a test . hand hygiene compliance data were collected at the unit level , and hospital - wide estimates were obtained by averaging all reporting units , weighted by patient - days for each respective unit . we also used a to compare the average historical hai rate from january 2013 until the implementation of the new program in october 2013 to the average hai rate during the study period of october 2013february 2015 , after implementation of the new program . we examined overall longitudinal hand hygiene compliance rates and hai rates during the new program by using generalized linear models to describe overall trends . to examine the association between hai and hand hygiene compliance , we used poisson regression using generalized estimating equations with an exchangeable working correlation matrix using sas version 9.3 ( sas institute , inc . , cary , nc , usa ) . we used data for hand hygiene compliance and number of overall hai , hai with multidrug - resistant organisms ( mdro ) , and healthcare - associated clostridium difficile infection ( ha - cdi ) from each nursing unit to estimate the overall association between hand hygiene and hai rates . an offset of patient - days was used to account for varying levels of time at risk for each unit and month . during the 17-month study period , we noted a significant increase in overall hand hygiene compliance rate ( p<0.001 ) and a significantly decreased overall hai rate ( p = 0.0066 ) , supported by 197 fewer infections ( figure ) and an estimated 22 fewer deaths ( 4 ) . overall healthcare - associated infection ( hai ) rate and hand hygiene compliance by month , october 2013february 2015 . the association between hand hygiene compliance and hai , adjusting for unit - level data , showed a 10% improvement in hand hygiene , associated with a 6% reduction in overall hai ( p = 0.086 ) . the association between hand hygiene compliance and ha - cdi , adjusting for unit - level data , showed a 10% improvement in hand hygiene , associated with a 14% reduction in ha - cdi ( p = 0.070 ) . no association was noted between hand hygiene compliance and mdro infections ( p = 0.7492 ) . hospital - wide hand hygiene compliance measurements by using the previous method ( covert observation by designated staff ) in the final measurement quarter were not statistically different than in the first month of compliance data measured by all staff in the new program ( p = 0.7503 ) . in addition , the average hai rate in the 9 months before implementation of the new program was not statistically different ( p = 0.542 ) from the average hai rate during the 17-month study period after implementation . when the cdc hand hygiene guideline was published in 2002 , hand hygiene compliance was summarized on the basis of then - current studies to be very low ( average 40% , range 5%81% ) ( 1 ) . investigators have demonstrated reductions in hai and mdro infections when compliance increased from low to medium levels ( 48% to 66% ) ( 6 ) . more recently , hospital epidemiologists and infection preventionists have worked to achieve and sustain higher compliance by using shared accountability , incentives , and feedback strategies ( 7 ) , but until now , no analysis has demonstrated whether an improvement in hand hygiene from a baseline high level ( > 80% ) to an even higher level ( > 95% ) would lead to hospital - wide decreases in hai ( 8) . demonstrating the importance of continuously improving hand hygiene compliance is critical for staff and hospital leaders who may underestimate the impact on hai . hand hygiene compliance measurements have been studied and methods have been proposed to alleviate concerns associated with interobserver variation , sampling bias , and the hawthorne effect ( 9 ) . we overcame these concerns by simplifying the compliance measurement to only evaluate the opportunities that cover most ( 87% ) of the world health organization defined five moments on the basis of a 24-hour validation video surveillance of activity in patient rooms ; that is , 21% of episodes before patient contact , 22% of episodes after touching a patient , and 44% of episodes after touching patient surroundings ( 10 ) . furthermore , by engaging all hospital staff in measuring hand hygiene compliance , all opportunities of the hygiene program were eligible opportunities for measurement . in this way , the hawthorne effect was a consistent presence that became the main intervention for achieving improvement . finally , the finding that our previous hand hygiene compliance rates measured by trained , designated staff was not statistically different than the compliance rates from the beginning of the new program further supports that the new compliance metric was not affected by any new , unanticipated measurement bias . although we can not eliminate the possibility that other infection prevention factors were also associated with a decreased hai rate , no other specific hospital - wide infection prevention goals were adopted during the time period of this analysis . the associations ( and absence thereof ) we found with hand hygiene and specific types of infections are biologically plausible . absence of association between mdro hai and hand hygiene is understandable because many mdro infections occur in patients who may be colonized before admission , have invasive devices , and are at increased risk for becoming infected with their own flora . however , c. difficile infections in healthcare facilities are predominantly spread through contact with infected patients or a contaminated environment , then carried on the hands of healthcare personnel . therefore , a weak association between ha - cdi reduction and hand hygiene improvement is plausible . although we adjusted the hand hygiene compliance data by patient - days , some units had patients at much lower risk for infections ( e.g. , psychiatric units ) . despite including units of varying risk for hai , we demonstrated that increased hand hygiene compliance improvements from already high rates can be an important strategy for achieving infection reductions , particularly for healthcare - associated c. difficile infections . a program designed to improve hand hygiene compliance among hospital staff successfully engaged all healthcare personnel in monitoring and improving their own hand hygiene compliance . this pursuit of excellence for hand hygiene compliance led to substantial hai reductions hospital wide .

improving hand hygiene from high to very high compliance has not been documented to decrease healthcare - associated infections . we conducted longitudinal analyses during 20132015 in an 853-bed hospital and observed a significantly increased hand hygiene compliance rate ( p<0.001 ) and a significantly decreased healthcare - associated infection rate ( p = 0.0066 ) .

greater than 80% of pavms are congenital , and approximately 50% of are associated with hereditary hemorrhagic telangiectasia ( hht ) . in addition to common complaints , such as dyspnea and epistaxis , a pavm can cause hemoptysis , hemothorax , and serious neurologic complications , such as stroke , seizures , and brain abscesses . ebstein 's anomaly ( ea ) is a congenital cardiac malformation characterized by downward displacement of the attachment of the septal and posterior leaflets of the tricuspid valve . ea is also a rare disorder , and patients with ea may have various additional cardiovascular anomalies . although the causes of a pavm and ea have not been established , embryogenic or genetic factors might give some contributions . however , there are no reports concerning the co - existence of pavms or hht with ea . we present a case of a pavm with ea that is suspected to have hht . she had experienced spontaneous recurrent epistaxis for the last several years , with no other remarkable medical history . a chest radiograph showed cardiomegaly and a well - demarcated , 12-mm nodular opacity in the left lung field ( fig . the electrocardiogram showed tall and broad p waves , as well as an incomplete right bundle - branch block . on transthoracic echocardiography , the displacement index ( distance between the mitral annulus and tricuspid annulus , divided by the body surface area ) was 15.6 mm / m , and it fulfilled the displacement index criteria for the diagnosis of ea ( 8 mm / m ) . moreover , tethering of the septal and posterior leaflets of the tricuspid valve was observed with central coaptation failure and severe regurgitation . a portion of the right ventricle was atrialized because of apical displacement of the tricuspid valve . she was diagnosed with ea , and agreed to undergo surgical treatment . to evaluate the nodule in the left lung , a 12-mm serpiginous vascular structure connecting the left interlobar pulmonary artery to the left inferior pulmonary vein was detected in the superior segment of the left lower lobe ( fig . no part of her medical history could explain the causes of secondary pavm , such as chest trauma , thoracic surgery , long - standing hepatic cirrhosis , metastatic carcinoma , mitral stenosis , or infections . three - phase contrast ct scans of the liver and mr angiography of the brain were performed to identify other visceral arteriovenous malformations . a liver ct showed diffuse dilatation of the hepatic arteries and veins with multifocal arteriovenous malformations , suggesting hht ( fig . the brain mr showed no evidence of vascular malformation . on the 7th day of admission , after discharge , she has remained stable and comfortable , and will undergo percutaneous embolotherapy of the pavm in the near future . a pavm is a rare pulmonary vascular anomaly with an incidence of 2 - 3 per 100,000 population.1 ) pavms may be single or multiple , and the left lower lobe of the lung is the most common location of solitary pavm.2 ) greater than 80% of pavms are congenital , and approximately 50% of these are associated with hht , also known as rendu - osler - weber disease.2)3 ) a single pavm < 2 cm in diameter on chest radiography usually does not cause symptoms.4 ) the most common complaint is epistaxis . a pavm can cause dyspnea , cyanosis , hemoptysis , hemothorax , and serious neurologic complications , such as strokes , seizures , and brain abscesses.4)5 ) patients with co - existing hht tend to have multiple arteriovenous malformations , rapid disease progression , and a higher complication rate.2 ) the brain , lungs , and liver are the most frequently involved organs in patients with hht.6 ) ea is a congenital cardiac malformation characterized by downward displacement of the attachment of the septal and posterior leaflets of the tricuspid valve.7 ) ea is also a rare disorder occurring in 1 per 200,000 live births.7 ) most cases are sporadic , and the embryologic and genetic contributors are unclear,8 ) but the ea gene might be located on chromosome 9.9 ) the genetic linkages to hht are located on chromosome 9 or 12.10 ) patients with ea may have various additional cardiovascular anomalies.8)11 ) however , there are no reports concerning the co - existence of a pavm or hht with ea . although it is unclear whether or not a concurrent pavm and ea has an embryologic or genetic relationship , we report a patient with a pavm and ea who was suspected to have hht according to the curaao criteria.12 ) further genetic and embryonic studies are needed to detect a possible relationship between the two medical conditions .

a pulmonary arteriovenous malformation ( pavm ) is a rare pulmonary vascular anomaly presenting as dyspnea or recurrent epistaxis . ebstein 's anomaly ( ea ) , a congenital cardiac malformation , is also a rare condition . there have been no reports concerning the co - existence of pavm with hereditary hemorrhagic telangiectasia ( hht ) and ea . a 40-year - old woman was admitted with a 2-month history of increasing dyspnea and several years of recurrent epistaxis . on transthoracic echocardiography , she was diagnosed with ea and agreed to undergo surgical treatment . a chest ct angiography showed a 12-mm serpiginous vascular structure suspicious for a pavm and a liver ct suggested htt . although it is unclear whether or not a concurrent pavm and ea have an embryologic or genetic relationship , we report a case of a pavm with ea . further genetic and embryonic studies are needed to identify a possible relationship of the two medical conditions .

bloc excision is mandatory but can represents a real technical challenge , expecially if tumor involves both the skull and the dura . the term primary intraosseous meningioma ( pim ) is used for an extradural meningioma that arises from the cap cells staying in the bone . they are mostly met at the periorbital and frontoparietal regions and they are , generally , devoid of neurological findings . other tumors that can involve the skull are hemangiomas , metastases , many type of carcinoma and sarcoma arising directly by bone or by contiguous tissue ( cutis , muscle , dura ) and invading secondarily the skull . the degree of resection is the most important factor correlating with recurrence and clinical long - term outcome . the aggressive surgery that is needed in these cases could bring a large bone defects to fill . the removal of a tumor involving the skull and the intracranial space could present a technical challenge , especially if the tumor has a dural and/or brain attachment . with a standard craniotomy , the maneuver of separating the intraosseus portion of the tumor from the intracranial portion might produce hemorrhage , traction and injury to the underlying brain . we describe a technique where the tumor involving the bone is before left in situ , normal dura is exposed around the tumor , and the tumor can be afterwards removed en bloc with direct vision and minimally traction of the brain surface . 8 patients , with different tumors involving both skull and dura , were treated with these technique . the histological examination of these patient s specimens showed : atypical meningioma , pim and anaplastic meningioma . below , we describe this technique used in the last patient treated , a man aged 45 with no neurological signs . patient underwent dcc , total surgical excision of pim and cranioplasty with peek custom made prothesis ( synthes ) . a 45 years old man , b.v . , presented to our department of neurosurgery with a mass arising from the right frontoparietal bone . he had not neurological signs and symptoms . computed tomography ( ct ) scan showed a homogeneous expansive bone lesion at the right fronto - parietal region , without contrast enhancement . on magnetic resonance imaging ( mri ) , the lesion was hypointense on t1- and t2-weighted images with no contrast enhancement after intravenous gadolinium administration , but contrast enhancement was seen at the adjacent dura . in the differential diagnosis , were first considered a fibrous dysplasia and primary bone tumors . patient undergoes tumor removal and cranioplasty with peek custom made prothesis ( synthes ) . under general anesthesia , the patient was positioned with the head turned approximately 30 toward the contralateral side , to expose the skull mass , with a pillow under the ipsilateral shoulder . the temporal muscle was splitted , the muscolar part that covering the tumor was left in situ for a completely radical resection and the remaining part was overturned . one only burr hole was performed laterally to the midline and we performed the first circle craniotomy around the lesion . then , using the same burr hole , a second and more enlarged circular concentric craniotomy was performed . there was no tumor in the bone ring and the dura beneath the ring was not involved . the inner surface of the dura was amply involved by the tumor , and it was dissected by the underlying brain surface under direct vision thanks to the space guaranteed by bone ring removal . the dural defect was repaired with pericardium bovinum patch and a peek custom made cranioplasty was performed ( fig 3 ) . tumor involving many tissues should be resected en bloc for minimizing risk of seeding and recurrency . in fact , meningioma with calvarial hyperostosis is commonly associated with an increased rate of recurrence if limited bone resection is performed . although radical excision of tumor involving the skull is the gold standard of oncological treatment , elevating a bone flap when the tumor involves both the skull and the dura could be very hard and represents a technical challenge . with a standard craniotomy this maneuver , done without direct vision , could produce hemorrhage and unwanted traction on the underlying brain surface . we have described a technique , a dcc , that permit to expose the normal dura surrounding the tumor and permit the resection of entire specimen with a direct vision of the underlying brain . in our opinion also have described a similar procedure for the removal of nail that was hammered in both the skull and the brain . sekhar et al . have utilized the concentric craniotomy technique for a fronto - orbital approach and ibarra - de la torre et al . for a posterior fossa craniotomy to protect the underlying dura and vascular structures . we believe that dcc is an optimal alternative on standard technique because permits the total removal of tumor involving both skull and dura structures , minimizing tractions on the underlying brain and permitting the direct vision during the dissection .

highlightsmany tumors can involve the skull . radical excision is the golden standard of treatment.elevate a bone flap when the tumor involves both the skull and the dura present a technical challenges.double concentric craniotomy is a safe and effective technique to remove tumor involving both skull and dura structures under direct vision .

the term nonconvulsive status epilepticus ( ncse ) is defined as a range of conditions in which electrographic seizure activity is prolonged and results in nonconvulsive clinical symptoms , . the clinical features of ncse may be subtle and diverse , and confirmation relies on the electroencephalogram ( eeg ) . several approaches to establishing criteria for ncse in adults have been published ( table 1 ) , , , and some clinical states may lie along an ictal interictal continuum . periodic discharges are often regarded on the interictal end of the spectrum , but when accompanied by clinical features including impaired vigilance and when signs resolve proximate to treatment , then this lends evidence to the ictal nature of periodic discharges along this spectrum . periodic lateralized epileptiform discharges ( pleds ) , in particular , have sparked controversy with regard to being part of the ictal vs. interictal spectrum . periodic lateralized epileptiform discharges can occur in the temporal vicinity of an overt seizure , thus reflecting an ictal interictal continuum phenomenon that can continue for weeks ( chronic pleds ) in conscious patients with retained alpha or basic rhythm . however , when they occur in a patient with altered level of consciousness , some authors regard it as ictal , , , , , , , , . since changes in mental status are common in epileptic encephalopathies and developmental delay such as in patients with cerebral palsy , it can be difficult or impossible to determine whether they are in status epilepticus , unless there is a discernible clinical improvement with treatment . we report the case of a patient with chronic epilepsy and cerebral palsy ( cp ) who presented with deterioration from an already impaired baseline . although the eeg revealed slow pleds which are not typical of ncse , the patient showed a good clinical and eeg response to benzodiazepines with pled regression . this 49-year - old man with cerebral palsy , mental retardation , and epilepsy residing in a long - term care facility for the prior 13 years had been awake , noncommunicative , but responsive to auditory and visual stimuli . he was treated with phenytoin and levetiracetam and had yearly breakthrough seizures over the prior 10 years . he had recently developed fever and dyspnea with a drop in oxygen saturation and was suspected of having aspiration pneumonia complicated by sepsis . he was given intravenous antibiotics , fluids , and supplemental oxygen and was transferred to our facility . following a mild generalized tonic clonic seizure , his examination remained persistently unchanged but he was now unresponsive to auditory , visual , and noxious stimuli , with a fluctuating level of alertness . plasma phenytoin level was low at 34.8 mol / l ( normal : 4080 mol / l ) . 1 ) showed intrusions of excess slow left - sided periodic lateralized epileptiform discharges ( pleds ) on a background of normal alpha pattern . administration of 1 mg of iv lorazepam resulted in resolution of the slow pleds ( fig . 2 ) and improvement in the patient 's neurological status , which now became responsive to auditory , noxious , and visual stimuli that occurred in a matter of 15 min after administration of lorazepam . by the next morning , his condition had greatly improved and he was near his baseline status . he received additional intravenous loading doses of phenytoin and levetiracetam on the same day , and his maintenance doses were adjusted . brain ct showed a large central meningioma as well as a small posterior fossa meningioma ( fig . review of his old brain ct films ( done seven years ago ) showed no such lesions . because of his poor quality of life and the risks involved , neurosurgery was not considered an option , and the patient was managed medically with antiepileptic medication . 4 ) , and the patient was discharged to a long - term care facility for further care . this patient with chronic epilepsy and cerebral palsy ( cp ) showed deterioration from a baseline that was already impaired , a finding described in ncse in those with developmental disability , . the eeg findings were not typical of ncse in that slow pleds lie in the gray zone along the ictal interictal continuum . cerebral palsy is a complex , heterogeneous lifelong condition with significant disability and long - term challenges that persist into adult life . epilepsy is reported in 35% to over 60% of patients with cp , and is more frequent in patients with more severe disability . sixteen percent of children with cp and epilepsy may develop nonconvulsive and/or convulsive status epilepticus . brain tumors , particularly primary ones , are associated more frequently with both convulsive and nonconvulsive status epilepticus , . electroencephalographic changes in mass lesions reflect irritability around the penumbra of the lesion , in this case , on the left . one can speculate that the focal structural lesion in the setting of chronic diffuse brain dysfunction , along with intercurrent infection and low aed levels , represented the multiple risk factors seen in the recurrence of seizures and appearance of ncse , . periodic lateralized epileptiform discharges ( fig . 1 ) consist of periodic spike - and - slow wave or sharp - and - slow wave complexes , typically with a frequency of 12 hz . in our patient , the frequency was ~ 0.5 hz . periodic lateralized epileptiform discharges occur in a variety of conditions such as strokes , tumors , and infections ; these together comprise around 50% of the underlying etiologies . slow growing extraaxial tumors such as meningiomas usually produce little eeg disturbance unless they compress and displace brain tissue or cause hydrocephalus such as in our case . periodic lateralized epileptiform discharges are reported to support a diagnosis of ncse if they meet certain conditions , in particular , good proximate clinical and eeg response to benzodiazepines with pled regression ( table 1 ) . when eeg and clinical regression are not clear , spect or pet scanning can guide the clinician in the possible ictal ( versus interictal ) nature of the periodic discharges , . there are diagnostic and management challenges in patients with long - term disability whose cognitive and neurological baselines are impaired and not always known to the clinical caregivers . additionally , a diagnosis of ncse may be difficult to make when this baseline is unknown and when the eeg findings represent a pattern that lies along the ictal interictal continuum . electroencephalogram can establish where along this continuum the patient resides , following which treatment that balances the risk benefit needs of the patient , and the needs of chronic caregivers , can then be provided and monitored so as to offer the patient the optimal chance for regaining lost function with minimal risk .

the presence of cerebral palsy and that of slow growing brain tumors are risk factors for convulsive and nonconvulsive status epilepticus . nonconvulsive status epilepticus ( ncse ) needs electroencephalographic ( eeg ) monitoring to be confirmed as it may be clinically subtle . furthermore , it may present with a variety of ictal eeg morphologies . we report a case of a patient with cerebral palsy and a large central meningioma . electroencephalogram showed a slow pattern of periodic lateralized epileptiform discharges ( pleds ) ( a pattern considered as being situated in the ictal interictal continuum ) on an alpha background . the patient was treated for ncse successfully with benzodiazepines followed by up - titration of his antiepileptic drug doses .

from january 1998 through may 2005 , a total of 2,421 fecal specimens were collected from children < 10 years of age ( median age 2.3 years ) with acute diarrhea in rio de janeiro , brazil . of these , 478 ( 19.7% ) specimens were collected from hospitalized children ( inpatients ) and 1,943 from outpatient children ( 341 [ 14.1% ] from the emergency department and 1,602 [ 66.2% ] from the walk - in clinic ) . of these samples , the median age was 12.5 months for rotavirus - positive patients and 12.2 months for adenovirus - positive patients . overall , of the hospitalized , emergency department , and walk - in clinic patients , 11.7% , 6.2% , and 10.0% , respectively , had samples positive for rotavirus , and 4.8% , 4.1% , and 4.4% , respectively , had samples positive for adenovirus . yersinia enterocolitica , campylobacter spp . , and shigella spp . were found in 8% of the specimens . , 1 rotavirus and salmonella spp . , and 1 rotavirus and e. coli ) . we selected 289 specimens that represented a random subset of samples that had prior negative results for rotavirus and enteric adenovirus . of these 289 , 117 were collected from inpatients and 172 from outpatients ( 89 emergency department and 83 walk - in clinic ) . suspensions of stool ( 10% ) were prepared in diethylpyrocarbonate - treated water and vertrel xf ( miller - stephenson , sylmar , ca , usa ) and clarified by centrifugation at 2,100 g for 10 min . we used 200 l of suspension for rna extraction with the nuclisens extraction kit ( organon tekninka , durham , nc , usa ) according to the manufacturer s instructions . the rna was eluted in 50 l of elution buffer and stored at 70c until use . a total of 240 samples were tested for norovirus rna by light cycler pcr that used primers and probes for orf1/orf2 junction region specific for norovirus gi and gii , as described ( 3,12 ) , and by the light cycler rna amplification kit hybridization probes ( roche , basel , switzerland ) . the 49 remaining samples were tested only by conventional rt - pcr , as described ( 5 ) . conventional rt - pcr was performed with the qiagen onestep rt - pcr kit ( qiagen , valencia , ca , usa ) . the rna samples were subjected to 1 cycle of reverse transcription ( 42c , 10 min ) followed by 5 min at 95c . pcr was performed for 40 cycles , each consisting of 1 min at 94c , 1 min at 40c ( for gi detection ) or 1 min at 44c for ( for gii detection ) , 1 min at 72c , and a final extension cycle of 10 min at 72c . we selected 6 samples that were positive by real - time light cycler pcr ( 2 gi and 4 gii ) for analysis by conventional rt - pcr with specific primers in capsid region d of norovirus gi and gii , as described above . the amplified cdna samples were purified from the gel by using qiaquick gel extraction kit ( qiagen ) , and the sequences were determined with the bigdye terminator cycle sequencing kit and the abi prism 3100 automated dna sequencer ( applied biosystems , foster city , ca , usa ) by using the same primers as used for the conventional rt - pcr . the nucleotide sequences of the amplicons were aligned with corresponding sequences of selected norovirus strains available in the genbank database and analyzed by using the clustal v algorithm of the megalign program in the dnastar software package ( madison , wi , usa ) . dq496212 , dq496213 , dq496214 , dq496215 , dq496216 , and dq496217 . of the 289 fecal specimens tested , 42 ( 14.5% ) were positive for norovirus : 36 ( 15% ; n = 240 ) by real time light cycler pcr and 6 ( 12.2% ; n = 49 ) by conventional rt - pcr . these percentages correspond only to single infections because we did not test samples already known to be positive for other pathogens such as rotavirus and adenovirus . positive samples and genogroups varied by year with no obvious yearly pattern ( table 1 ) . the winter vomiting disease , we detected infection throughout the year , with no seasonal pattern ( figure ) . norovirus infections were equally common among outpatients and inpatients . among 117 inpatients , 18 ( 15.4% ) had positive norovirus test results compared with 24 ( 14% ) of 172 outpatients ( 11 emergency department and 13 walk - in clinic ) . although the disease caused by norovirus is described as mild ( diarrhea , vomiting , abdominal pain , and fever ) and generally does not lead to hospitalization ( 13,14 ) , of 42 norovirus - infected children , 29 ( 69% ) were either hospitalized or received medical care in the emergency department , which suggests that they had a more severe illness . only 13 ( 31% ) of the 42 norovirus - infected children attended the walk - in clinic , which suggests that they had mild disease ( table 2 ) . other than diarrhea , fever was the most common symptom among the 42 norovirus - positive patients in this study , reported for 11 ( 26.2% ) patients . vomiting only was described for 8 ( 19.0% ) ; vomiting and fever was described for 6 ( 14.3% ) . no mixed infection with bacteria seasonal distribution of norovirus ( nov ) infections in rio de janeiro , brazil , 19982005 . although norovirus belonging to genogroup gii is considered the most prevalent strain worldwide ( 79,11,15 ) , we found no important difference in the prevalence of the 2 genogroups detected in our study . overall , 20 ( 48% ) of the 42 samples were identified as genogroup gi and 22 ( 52% ) as gii ( table 1 ) . no statistically significant difference in the prevalence of gi and gii was observed between inpatients and outpatients . our study documents that noroviruses are a common cause of acute gastroenteritis in children who are inpatients or outpatients in brazil and are likely second only to rotavirus as a cause of severe childhood diarrhea . nonetheless , it documents how common norovirus infections may be and indicates that further study will be necessary to assess their role among brazilian children , to understand the epidemiology of the disease , and to seek evidence of immunity in children , which might encourage development of a vaccine .

during 19982005 , we analyzed stool samples from 289 children in rio de janeiro to detect and genotype norovirus strains . previous tests showed all samples to be negative for rotavirus and adenovirus . of 42 ( 14.5% ) norovirus - positive specimens , 20 ( 47.6% ) were identified as genogroup gi and 22 ( 52.3% ) as gii .

klippel - feil syndrome ( kfs ) is a rare condition characterized by the congenital fusion of any two of the seventh cervical vertebrae . sprengel 's deformity ( sd ) is a congenital structural abnormality of the shoulder girdle ; receive surgical treatment as a child or adolescence . the omovertebral bone is characterized as an abnormality in the musculoskeletal system . in this anomaly , however , some studies reported association between sd and omovertebral bone and introduced it as kfs . shoulder girdle anomaly concomitant with muscle disorder such as hypoplasia or atrophy are called sd . vertebral fusion of cervical spines is rare , but it is possible to occur in that spines . first symptoms that they explained were including short neck , restricted motion of the neck , and low hairline . after that time the prevalence of this syndrome is unclear , but some studies believe that its prevalence is about 1 in 40,000 of alive newborns . furthermore , this syndrome affect female more than male . it should be considered in the setting of neurological symptoms characteristic of cervical myelopathy in patients with obvious skeletal dysmorphias of unknown etiology . short neck , low hairline , and restricted neck motion are diagnostic triad is present in less than half of the patients . we report a 50-year - old woman who suffered from neck pain and ataxia for a long time . to the best of our knowledge she presented with a 2 years history of neck pain and ataxia for 1 year . she had n't urinary incontinence and she was referred to a neurosurgeon by a neurologist because of her progressive gait ataxia . neurological examination showed intact cranial nerves and no motor deficit , but we found impairment in pain sensory and light touch in both legs that was prominent on the right side of the body , hyperreflexia in the left knee , ankle jerk , and mild gait ataxia based on tandem and blind walking . physical examination revealed a short neck , a low occipital hairline and diminished cervical range of motion . the patient also had an elevated left scapula and a bony prominence extending from the shoulder to the neck . anteroposterior and lateral radiographs revealed fused vertebral body of c5-c6 without spina bifida [ figures 1 , 2a and b ] . multislice computed tomography , three dimensional ( a ) computed tomography ( b ) oblique view ct postroanterior view radiographs in flexion and extension position demonstrated neither vertebral instability nor narrowing of the retrodental distance in ante- and retroflection . subsequent magnetic resonance ( mr ) and computed tomography imaging with three dimensional reconstructions of the neck and shoulder revealed an atypical bone configuration of the left shoulder with elevation and dysplasia of the scapula and an aberrant bony structure extending from the superomedial border of the scapula to the c5 transverse process leading to constriction of the spinal canal [ figures 13 ] . resection of the omovertebral bone and decompression of the spinal canal were indicated with respect to patient 's clinical myelopathy . a curved incision was performed over the omovertebral bone from its cervical origin to its scapular termination . the intraspinal localized aberrant bony fragment , which we considered responsible for the neurological syndrome , was removed from the cleft in the posterior arch of c5 , a laminectomy was performed at that level , and the omovertebral bone was partially resected . in terms of gait ataxia the patient was neurologically unchanged , but she experienced a significant reduction in her neck pain , improved range motion of the neck , and the cosmetic result was good immediately after the operation . she recovered well from the procedure and was discharged from the hospital 3 days post - operatively . maurice klippel and andre feil explained a syndrome separately that is defined by a clinical triad include short neck , restricted range of motion in the neck and low posterior hairline . after that time , some patients with this syndrome found extra anomalies that can be accompanying to kfs . the prevalence of kfs has been reported about 1 of 40,000 or 1 of 42,000 persons and most of them are female . present case was a woman who had mentioned triad . according to the level of vertebral fusion , some studies classified it into three groups : ( 1 ) many vertebras in cervical and thoracic zone are fused to each other , ( 2 ) fusion is seen in one or two vertebra like a fusion between c2-c3 or c5-c6 , and ( 3 ) vertebras are associated with each other in cervical and thoracic or lumbar zone accompany with other anomalies . our patient had fusion between c5-c6 with an elevated left scapula and a bony prominence extending from the shoulder to the neck . torticollis and loss of symmetrical expression of the face has been reported in 10% and 11.5% of cases with kfs respectively . our patient that was a rare presentation in that age had multiple anomalies including sd , omovertebral bone , and scoliosis . as it is mentioned , symptoms and signs that point to kfs are various and it can present as cosmetic problems or severe problem such as predisposing to severe neurologic damage . thus , sometimes it is introduced as an emergent situation and if you misdiagnose it , it will remain serious neurologic sequel . sd is another anomaly that is seen in 7 - 42% of cases with kfs . muscular dysfunction resulted from some common defects in the trapezius , rhomboids and levator scapulae and some uncommon defects in muscles such as the pectoralis major / minor , latissimus dorsi , sternocleidomastoid , and serratus anterior . this process is started at levels of 4 - 6 cervical spines and then it descends to normal location opposite to second to seventh vertebra of thoracic . events that happen in that time can cause sd omovertebral bone is seen in 25 - 35% ( even 50% in some studies ) of patients who are suffered from sd . in fact , it is a cartilaginous or bony and or fibrous tissue with a firm covers that fuse the scapula and processes of cervical spines . conservative treatment is not acceptable in sd and surgery usually is useful for removing deformity . however , when physicians make a diagnosis and plan treatment , they should search the features of kfs and sd . the case of a unilateral sd and kfs as an etiology for cervical myelopathy is unique in the adults . risk for brachial plexus injury because of compression or stretching by the clavicle accelerate with age . therefore , the surgical approach of adults patients with sd can intend suitable surgical conclusions .

klippel - feil syndrome is a rare condition characterized by the congenital fusion of two of the seventh cervical vertebrae . a 50-year - old woman presented with a 2-year history of neck pain and ataxia for 1 year . she had not urinary incontinence . she was referred to a neurosurgeon by a neurologist because of her progressive gait ataxia . risk for brachial plexus injury because of compression or stretching by the clavicle accelerate with age . therefore , the surgical approach of adults patients with sprengel 's deformity can intend suitable surgical conclusions .

one of the methods of partial ureter substitution is the use of free bladder autologous mucosa flaps . this method has been in use for about 50 years . despite previous reports describing the benefits of this method , in reconstructive surgery , up to now , it has not been used in clinical practice . our poor morphologic results with the use this method prompted us to perform microangiography of the newly constructed part of the ureter with this method to definitively resolve the problem of neovascularization in this area . the experiments were carried out on 29 mongrel dogs , as previously described [ 14 ] . all animals were operated on in the same manner ( figure 1 ) , with general endotracheal anesthesia . after grafting , four of the experimental animals were additionally subjected to perfusion of the vascular bed with a radiopaque medium called micropaque ( barium sulphuricum ) ( nichols roche , france , distributed by schering germany ) . this was done to ascertain neovascularization in the supplemented part of the ureter by a tube constructed from the free mucosa flap of the urinary bladder . microangiography was performed after a longitudinal median laparotomy of 34 cm over the kidney vessels . the aorta was ligated and a cannula connected with the perfusion set ( figure 2 ) was inserted into the aorta . to avoid errors in performing the operation and interpreting our results , we carefully studied the literature [ 512 ] and consulted with other investigators about the principles of this kind of experiment . the perfusion of 500 ml 30% micropaque ( barium sulphuricum ) ( nichols roche , france , distributed by schering germany ) , with 0.9% nacl was transfused and subsequently 30% micropaque ( barium sulphuricum ) ( nichols roche , france , distributed by schering germany ) with 10% buffered formalin . perfusion was performed under constant pressure of 140/80 mm hg , at the temperature of 37c , for 30 min . after the procedure , all the experimental animals were euthanized and the samples were harvested and stored for 6 h at 20c . then , a segment of ureter measuring 10 cm in length was excised ( 5 cm above and 5 cm below the graft suture site ) , showing the surface vessels filled with micropaque ( figure 3 ) . at the end of the procedure , the specimen was stitched on the celluloid plate and harvested with 10% formalin , buffered to 7.6 ph . after 14 consecutive days , the specimens were irradiated to show the visible net of the new vascular bed ( figure 4 ) . then , they were cut into 2-mm - thick slices using a microtome and were irradiated by direct exposure and visualized on celluloid film . exposure time was 10 min , electric voltage 20 kv , and current intensity 5 ma . we used single - sided celluloid film type tn-12 , ( bydgoszcz manufacturing fotochemic plant , poland ) , which allowed us to obtain image of capillaries of up to 100200 , because these celluloid films contain a one - sided photosensitive layer . a stepwise process of the ureter substitutions from 1 dog is shown in figures 13 . microscopic evaluations showed the complete regeneration of the mucosa of the supplemented ureteral segment [ 14 ] . the defects in the ureters were not bridged by the smooth muscle [ 14 ] . the experimental findings showed a massive periureteral fibrosis , due to reparative or reactive process , which was considered as the main reason for the failure of our interventions [ 14 ] . one of the most common causes of scarring or stricture of the ureters is ureter surgery . the reason for this is that the arteries going to the uterus are very close to the ureters . during surgery , the amount of scarring and inflammation that occurs after surgery can be very dense and as a consequence leads to hydronephrosis and destroying the kidney . previous reports described the benefit of free autologous bladder mucosa graft for the reconstruction of the ureter . however , unpublished observations have generated a significant interest and a need to re - evaluate autologous ureter grafts constructed from the free autologous mucosa flap ; therefore , this method has not been used in clinical practice . it should be noted that the results of our previous studies [ 14 ] and of the present study do not support a free bladder mucosa flap as a viable clinical therapy for ureteral reconstruction , in spite of the positive reports of the above - mentioned authors . the present animal study suggests that the surgical ureteral reconstruction using this method or grafted tissue is not suitable to achieve clinically desirable results .

backgroundthere is a paucity of data addressing the blood supply in the surgically reconstructed ureter , and complete lack of microangiographic studies of the reconstructed ureter with the use of a free bladder mucosa flap . the present study evaluated the blood supply in the reconstructed dog ureter after a 5-centimeter segment resection , supplemented by a tube constructed from a free bladder mucosa flap.material/methodsfemale mongrel dogs ( n=29 ) were used in this study . under general anaesthesia , a 5-centimeter autologous free bladder mucosa flap was used to construct a tube , which was afterwards grafted to replace a 5-centimeter ureter resection . after a period of 3 months ( n=2 ) and after 1 year ( n=2 ) , microangiography was performed to assess the revascularization of the grafted ureter.resultsin our study , we observed the continuity of the ureter , but the grafted reconstruction was narrowed by the cicatrization in about 86% ( n=25 ) of cases . this resulted in the development of hydronephrosis , as described in previous publications . the ureteral wall was covered by a normal urothelium , but consisted of fibrous connective tissue , which failed to restore a regular ( normal ) coat . the reconstructed segment showed no smooth muscle cells . a few smooth monocytes were found only at the border with intact portions of the ureter . the microangiography performed at the end of the experiments showed no vascularization of the restored segment of the ureter.conclusionsthe experiments showed a whole regeneration of urothelium in the transected and reanastomosed ureters . however , there was no regeneration of the muscular coat and a complete lack of revascularization .

the classification and the terminologies used for various vascular lesions have been very confusing despite the fact that a biological classification was first published in 1982 by mulliken and glowacki . this classification was later adopted by the international society for the study of vascular anomalies ( issva ) in their first workshop held in rome during june 1996 . this continuing workshop now takes place every 2 years in various countries around the world . the issva is an organization comprising of specialists in various disciplines interested in vascular anomalies and was founded in 1992 in budapest with the aim of achieving consensus among health care professionals on the terminology , to further the knowledge of pathogenesis , diagnosis and treatment of these vascular lesions . an analysis of various scientific articles and latest edition of text books showed that significant confusion still prevails due to the indiscriminate , inappropriate and interchangeable use of various terms . historically benign vascular tumors were classified : ( 1 ) according to the type of fluid they contained as hemangioma ( blood - containing lesion ) and lymphangioma ( lymph - containing lesion ) and ( 2 ) according to the size of the vascular channels as capillary ( small diameter vascular channels ) and cavernous ( large diameter vascular channels ) . mulliken and glowacki described a biological classification based on endothelial cell characteristics , physical findings and natural history , that differentiates vascular lesions with endothelial cell proliferation ( example hemangioma ) from lesions with structural anomalies ( vascular malformations ) . the issva modified it in their continuing workshops , differentiating vascular tumors from vascular malformations based on their clinical appearance , radiological features , pathological features and biological behaviour [ table 1 ] . historically benign vascular tumors were classified : ( 1 ) according to the type of fluid they contained as hemangioma ( blood - containing lesion ) and lymphangioma ( lymph - containing lesion ) and ( 2 ) according to the size of the vascular channels as capillary ( small diameter vascular channels ) and cavernous ( large diameter vascular channels ) . mulliken and glowacki described a biological classification based on endothelial cell characteristics , physical findings and natural history , that differentiates vascular lesions with endothelial cell proliferation ( example hemangioma ) from lesions with structural anomalies ( vascular malformations ) . the issva modified it in their continuing workshops , differentiating vascular tumors from vascular malformations based on their clinical appearance , radiological features , pathological features and biological behaviour [ table 1 ] . hemangiomas grow by endothelial cell hyperplasia and should be differentiated from vascular malformations , which are not true neoplasms but are localized defects of vascular morphogenesis caused by dysfunction in embryogenesis and vasculogenesis [ table 2 ] . the greek suffix means cellular proliferation of a tumor and thus the term hemangioma is erroneous when used for malformations . hemangiomas are the most common benign soft tissue tumor of infancy and childhood , occurring in 12% of all infants and are found in greater frequency in girls , whites , premature infants , twins and are usually born to mothers of higher maternal age . they occur most frequently in head and neck region ( 60% ) , followed by the trunk ( 25% ) and the extremities ( 15% ) , which are grouped into infantile hemangiomas ( ihs ) and congenital hemangiomas ( chs ) . differences between infantile hemangioma and vascular malformations ihs ( outdated term juvenile hemangioma ) arises during the first 8 weeks of life as an area of discoloration or telangiectasia . the lesion exhibits a rapid proliferative phase during early childhood for 6 - 12 months and grows into a raised rubbery bright - red tumor ( resembling a strawberry , hence outdated term strawberry hemangioma ) . this is followed by gradual involution and a spontaneous regression by the age of 5 - 9 years . 50% of all hemangiomas will completely involute by the age of 5 years and 90% by the age of 9 years . 40% of involuted lesions may either show scaring , wrinkling , telangiectasia , or loose fibro - fatty tissue . ihs can be grouped into focal , segmental and indeterminate , or depending on the depth of the lesion from the skin surface as superficial , deep and mixed . focal ihs are the most common variant , appearing as localized raised tumor - like lesion that tends to occur at the area of embryological fusion . segmental ihs are flat plaque - like larger lesions that show a geographic segmental distribution and indeterminate ihs shows characteristics of both focal and segmental ihs . color varies with the depth of the lesion ; they can be bright red ( superficial ) , purple , blue , or normal skin colour ( deep ) . chs are clinically present as fully developed lesions at birth and either rapidly involutes during the first year of life or may never show involution . these lesions do not exhibit a proliferative phase and do not grow after birth . rapidly involuting congenital hemangiomas ( rich ) are present at birth , either as red - purple color plaques with coarse telangiectasia , or as flat violaceous lesions , or as a raised greyish tumor surrounded by a pale halo with multiple tiny telangiectasia . rich undergo a rapid regression phase and completely disappear by 12 - 18 months of age . non involuting congenital hemangiomas ( nich ) are also present at birth , appearing as pink or purple colored plaque - like lesions with prominent overlying coarse telangiectasia and peripheral blanching . nich do not show a regression phase and grows proportionately with the growth of the child . differences between congenital and infantile hemangioma apart from hemangiomas of soft tissue , scientific literatures have reported central hemangiomas ( hemangioma of bone ) and intramuscular hemangiomas . many researchers in addition to the world health organization ( who ) believe that most if not all such proposed lesions are vascular malformations rather than true neoplasms . therapeutic guidelines , management and follow - up of hemangiomas and vascular malformations differ and are beyond the scope of this article . a good classification is important for categorising information , recording data , proper communication , guiding treatment plans , obtaining prognostic information and should be easy to understand and applied by the clinicians . it is our duty to be consistent in our terminology and classification of vascular lesions in all our scientific writings and presentations in order to communicate effectively , understand its pathophysiology , promote research and develop newer therapeutics . terms to be avoided when describing these lesions include angioma , birthmarks , capillary hemangioma , cavernous hemangioma , juvenile hemangioma , strawberry hemangioma and inappropriate interchangeable use of the terms hemangioma and vascular malformation .

despite the fact that a biological classification of congenital vascular tumors and malformations was first published in 1982 by mulliken and glowacki , significant confusion still prevails due to the indiscriminate and interchangeable use of the terms hemangioma and vascular malformation . hemangiomas are true neoplasms of endothelial cells and should be differentiated from vascular malformations which are localized defects of vascular morphogenesis . on an analysis of various scientific articles and latest edition of medical text books an inappropriate use of various terms for vascular lesions was found , contributing further towards the confusion . the widely accepted international society for the study of vascular anomalies ( issva ) classification differentiates lesions with proliferative endothelium from lesions with structural anomalies and has been very helpful in standardizing the terminologies . in addition to overcoming obstacles in communication when describing a vascular lesion , it is important that we adhere to the correct terminology , as the therapeutic guidelines , management and follow - up of these lesions differ .

a coracoid fracture is a rare orthopaedic condition as it accounts for only 2 10 % of all scapular fractures and < 0.1% of all fractures . in even rarer cases coracoid fractures we present an unusually rare case of a simultaneous fracture of the coracoid process and the lateral end of clavicle . the patient was treated with shoulder arm sling for 6 weeks followed by physiotherapy . at 6 months follow up the patient was pain free with full range of motion at right shoulder . concomitant fractures of lateral end clavicle and coracoid process are rare and may not be visible of plain radiographs . ct scan may be indicated if the clinical examination suspects additional injuries of shoulder girdle . coracoid fractures alone are themselves a rare occurrence amounting to approximately < 0.1% of all fractures and even only 5% of all fractures of the shoulder [ 1 - 3 ] . no reliable figures currently exist to determine the prevalence of a simultaneous distal clavicle and coracoid fracture . a 60 year old gardener presented with a history of injury to her shoulder as her arm was pulled by a lawn mower . the patient did not have any previous injury or degenerative condition to this shoulder prior to this accident . physical examination showed swelling and bruising around shoulder , tenderness and restricted movements of the right shoulder . ct and plain radiographs of the shoulder displayed a displaced coracoid fracture and non - displaced fracture of the distal end of clavicle at the time of injury ( fig . the patient was placed in a shoulder arm sling for six weeks and was then referred to physiotherapy . some doubtful angulation of the coracoid process is visible but fracture is not appreciated clearly . 1b- ct scan conforms the fracture of lateral end of clavicle and also displace coracoid fracture . at three months the patient was pain free and back to working as a gardener with a free range of movement in the right shoulder . 3 months follow up radiographs showing no further displacement of the fracture with early consolidation at the fracture site . when fractures of coracoid and distal clavicle co - exist , misdiagnosis is common because both the fractures may not be seen on standard projections . the stryker notch view is recommended for detection of these fractures . furthermore ct imaging is advised if radiographs initially fail to show any bony injuries of the shoulder , but clinical examination suggests otherwise . the mechanism of injury is probably the result of a resisted flexion of the arm and elbow which led to a forceful pull of the muscles , pectoralis minor and the coracobrachialis , that insert into the coracoid . this has previously been described in two other case studies concomitant coracoid fractures and acromioclavicular dislocation . the patient suffered an ipsilateral avulsion of the coracoid which would be considered as a type ii according to ogawa et al and a distal clavicle fracture which would be considered as a type i according to the neer s classification . it is to this day still controversial how to treat coracoid or distal clavicle fractures individually , let alone if they are present concomitantly . details and consequent treatment methods of coracoid fractures have also yet to be established in literature . ogawa et al have recommended surgical treatment of coracoid fractures combined with other shoulder injuries , but have otherwise shown similar outcomes between operative and non - operative treatment of coracoid fractures alone . they did however recommend non - operative management of type ii fractures as these do not disturb the scapuloclavicular connection . there does not seem to be a general consensus on the treatment of distal clavicle fractures too . robinson et al have recommended non - operative management of distal clavicle fractures in the middle aged or elderly patients . out of the 101 patients treated non - operatively with distal clavicle fractures , only in 14% of cases rokito et al compared nonoperative and operative treatment of a total of 30 type ii distal clavicle fractures retrospectively and did not reveal any significant difference in terms of ucla , constant and asesscore . on the other hand haidar et al and meda etal advocate the use of clavicular hook plates . these studies however did not compare the operative treatment to non- operatively treated control groups [ 10 , 11 ] . the option of treating a symptomatic nonunion of the distal clavicle was described by kang et al who achieved 100% bone union in 10 patients following orif with an oblique locking t - plate and autogenous bonegraft . lasda et al described successful treatment of a concomitant acromioclavicular dislocation and coracoid fracture conservatively . eleven years later carr et al further described two cases of concomitant coracoid fracture and acromioclavicular dislocation which were treated conservatively with good results . recently duan et al published a case report of operative treatment of an acromioclavicular dislocation in combination with a coracoid fracture which was treated with a hook plate . they described the problem of only partial bone union after 5 months and the additional plate removal that needed to be done 12 months after the initial operation . only one case report by ruchelsman however has described the operative treatment of a concomitant lateral clavicle and coracoid fracture . in his case he then proceeded with a open distal clavicle excision and reduction of the coracoclavicular interval with screw fixation achieving an excellent clinical outcome . they commented that high index of suspicion is needed to avoid missing such combination injuries at shoulder girdle and additional radiological investigations should be done if pain at shoulder girdle is persistent . in view of the sparse and controversial literature available , we believe that the patient should be appropriately informed of both operative and nonoperative options treatment options . in our case the patient preferred nonoperative management which resulted in an excellent clinical result . concomitant fractures of lateral end clavicle and coracoid process are rare and may not be visible of plain radiographs . ct scan may be indicated if the clinical examination suspects additional injuries of shoulder girdle . even in cases with displacement a conservative management will result in a good clinical outcome as seen in our case .

introduction : a coracoid fracture is a rare orthopaedic condition as it accounts for only 2 10 % of all scapular fractures and < 0.1% of all fractures . in even rarer cases coracoid fractures are also associated with other bony injuries of the shoulder . there is currently no consensus on the treatment of such injuries.case report : we present an unusually rare case of a simultaneous fracture of the coracoid process and the lateral end of clavicle . the patient was treated with shoulder arm sling for 6 weeks followed by physiotherapy . at 6 months follow up the patient was pain free with full range of motion at right shoulder.conclusion:concomitant fractures of lateral end clavicle and coracoid process are rare and may not be visible of plain radiographs . ct scan may be indicated if the clinical examination suspects additional injuries of shoulder girdle . we have treated this injury non operatively with a good clinical outcome .

the presence of butterfly rash is typically a sign of systemic lupus erythematosus ( sle ) , but it can also signal a dermatologic disorder . typically , butterfly rash appears in a malar distribution across the nose and cheeks . the case report presented here is of a 40 year old female with bright red discoloration of the skin involving the malar region bilaterally with the bridge of the nose and chin along with typical bright red colored swollen gingiva with shallow periodontal pockets and loss of attachment . both the lesions exacerbated and relieved almost simultaneously which led us to correlate this dermatological condition to oral lesion . a 40 year old female reported to the department of periodontics , institute of dental sciences , bareilly , with the chief complaint of swelling and bleeding from gums associated with burning sensation since last two years and bright red discoloration of the skin involving the malar region bilaterally , bridge of nose and chin . extraoral examination revealed malar rash involving the chin accompanied by yellowish white pustules scattered along the discoloration . the discoloration appeared first on cheeks , followed by nose and finally the chin as shown in figure 1 , 2a , 2b , 2c , 2d . the discoloration was followed by acne , followed by pustules and finally the scar which healed by itself followed by its reappearance after 10 - 15 days . bright red discoloration of the malar region and chin histopathologic picture showing inflammatory cells , blood vessels and connective tissue stroma intraoral examination revealed bright red discoloration of the gingiva involving the marginal , interdental and attached gingiva extending from # 14 to 22 and # 43 to 31 and mild generalized inflammatory enlargement was noticed [ figure 2 ] . detailed history from the patient revealed that the bleeding from gingiva was insidious , mild , intermittent , occurred only while brushing the teeth and aggravated on eating hard fruits . it appeared first in the interdental region and then progressed to involve the other parts of gingiva . swelling increased in size gradually , decreased thereafter two months for about 15 days , then regains its original size . radiographic findings [ figure 3 ] showed features of chronic generalized periodontitis with horizontal pattern of bone loss and angular defect at some sites . opg - features of chronic generalized periodontitis with horizontal pattern of bone loss and angular defect at some places laboratory investigations carried out included routine blood investigations , le cell phenomenon , ana studies ( antinuclear antibody studies ) , anti ds dna ( anti double stranded dna ) . incisional biopsy of the specimen illustrated the presence of connective tissue stroma with eroded epithelium . as the intraosseous lesion was interfering with mastication and extraoral with aesthetics , the patient was subjected to phase - i therapy ( oral hygiene instructions , scaling and root planning ) , antibiotic ( doxycycline ) was prescribed for five days followed by tapered dose for two days , mouthwash ( listerine ) for 1 month , topical corticosteroid ( betamethasone ) for extraoral application 3 times a day for 4 weeks . when the patient did not respond to the , systemic corticosteroids were administrated ( tab wysolone 5 mg for 15 days ) . she was asked to wear the sunscreen with a sun protection factor ( spf ) of 15 or higher to protect her face from sun , avoid irritating the facial skin by rubbing or touching it too much , avoid the use of facial products that contain alcohol or other skin irritants and the use of non - comedogenic products was recommended . post - treatment : disappearance of acne , pustule , reduction in erythema after one month : edema disappeared , burning sensation reduced , persistent erythema over # 12 , 11 butterfly rash is a red , flat facial rash involving the malar region bilaterally and the bridge of the nose . it is most suggestive of systemic lupus erythematosus , but it might be seen in variety of other dermatologic diseases such as erysipelas , rosacea , seborrheic dermatitis , sarcoidosis , polymorphous light reaction etc . rash may appear as a prominent , non - scaling , intermittent erythema limited to lower half of the nose or including the chin , cheeks and central forehead . the malar rash often appears or gets worse after sun exposure ( photosensitivity ) or stress that causes an increase in the circulation to the skin . sometimes the butterfly rash appears on other parts of the body as well , usually on the trunk , arms or legs . the reason the malar rash is shaped like a butterfly is because it follows the angle that the uv rays land on skin . it is caused by a malfunctioning immune system , which causes the body to attack healthy tissues in the skin . the present case is of a 40 year old female who presented with a butterfly shaped rash involving the chin and the forehead along with gingival manifestations . the intraoral clinical picture could be suggestive of an inflammatory lesion but the picture did not improve completely after phase - i therapy . on the basis of the clinical findings , the tentative diagnosis of lupus erythematosus was made , with the differential diagnosis of erysipelas , polymorphous light reaction , rosacea , seborrheic dermatitis , and sarcoidosis . in the present case there was no systemic involvement and special investigations like ana ( anti - nuclear antibody ) and anti double stranded dna were negative so sle was ruled out . there was no history of previous throat infection , fever and leukocyte count was within normal limits , thus no evidence of erysipelas . the extraoral appearance was neither patchy nor thick adherent crusts , so seborrheic dermatitis was also ruled out . the patient presented with persistent redness , presence of pustules , absence of black heads , burning and stinging sensation along with gingival enlargement and discoloration which signaled rosacea . management of the dermatological disorder associated with oral involvement is often a complex undertaking and requires a joint expertise and communication of clinicians to provide the patient with an optimal treatment plan based on scientific rationale . all that glitters is not gold similarly all the butterfly rashes are not lupus erythematosus so a dentist should look into and treat accordingly .

rashes can occur in any part of the body . but rash which appears on face has got both psychological and cosmetic effect on the patient . rashes on face can sometimes be very challenging to physicians and dermatologists and those associated with oral manifestations pose a challenge to dentists . butterfly rash is a red flat facial rash involving the malar region bilaterally and the bridge of the nose . the presence of a butterfly rash is generally a sign of lupus erythematosus ( le ) , but it can also include a plethora of conditions . the case presented here is of a female with butterfly rash along with typical bright red discoloration of gingiva . the clinical , histopathological and biochemical investigations suggested the presence of rosacea .

an increased incidence of hashimoto thyroiditis has been reported in patients with turner syndrome . in view of its pathogenic relationship with autoimmune thyroiditis we report the case of a 9-yr - old girl with turner syndrome who developed graves disease during recombinant human gh therapy , and we discuss previous reports of this association . the patient was the first child of healthy unrelated parents of normal stature , father 175.0 cm and mother 159.0 cm . the patient was born after an uncomplicated pregnancy at a gestational age of 37 wks and 1 d. her birth weight was 2490 g. on examination , lymphedema and webbed neck were detected . chromosomal analysis of peripheral blood lymphocytes ( n=26 ) showed complete deletion of the short arm of the second x chromosome ( karyotype : 45 , x ) . at the age of 5 yr and 2 mo , her height was 98.2 cm ( 2.25 sd ) and her weight was 14.4 kg ( 1.48 sd ) . a gh stimulation test was performed , and the peak gh values after stimulation with clonidine and arginine were 8.39 ng / ml and 5.56 ng / ml , respectively . of note is that diagnosis of complete gh deficiency is less than 5 ng / ml in this assay . recombinant human ( rh ) gh therapy ( 0.175 mg / kg / wk ) was initiated with success ( fig . thyroid function tests showed a tsh level of 0.01 u / ml ( normal , 0.50 to 5.50 u / ml ) , a free ( f ) t4 value of 6.00 ng / dl ( normal , 0.85 to 1.80 ng / dl ) , and a free t3 value of 21.76 pg / ml ( normal , 2.50 to 5.50 pg / ml ) . anti - thyroglobulin antibody was 3.4 u / ml ( normal , < 0.3 u / ml ) . anti - thyroid peroxidase antibody was 5.5 u / ml ( normal , < 0.3 u / ml ) . tsh receptor antibody ( trab ) was 52% ( normal , < 15% ) . these results are compatible with a diagnosis of graves disease and treatment with thiamazole was started . growth curve of the patient at the latest follow up ( 9 y old ) , the development of the patient s breast was tanner stage 1 . treatment with thiamazole was continued and the thyroid function has stayed within normal ranges . the association of turner syndrome with graves disease was reported in english about 1020 years ago ( 1,2,3,4,5,6,7,8,9,10 ) . table 1table 1 graves disease in turner syndrome summarizes the historical thirteen known cases of graves disease with turner syndrome , including our case . this table reveals that the clinical characteristics of graves disease with turner syndrome are similar to those known generally in patients without turner syndrome in terms of ages of the onset , symptoms and prognosis . treatment with rhgh was given to 4 patients in table 1 , and it was continued in 3 out of the 4 patients including our case . this continuation of gh treatment , together with the successful treatment of hyperthyroidism , suggests that a direct link between gh treatment and graves disease is unlikely . consistent with this hypothesis , the incidence of hyperthyroidism in japanese patients with turner syndrome receiving rhgh therapy is 0.40% , which is similar to overall incidence of hyperthyroidism in patients with turner syndrome , 00.5% ( 11 , 12 ) . it is well known that hyperthyroidism in patients with turner syndrome leads to acceleration of height velocity ( 6 , 13 ) . in our patient , the height velocity was not increased by hyperthyroidism , probably because her growth had been already accelerated by rhgh therapy before the onset of hyperthyroidism . it is important to monitor changes of thyroid function as well as growth parameters in patients with turner syndrome , as is recommended by sybert and mccauley ( 14 ) .

an increased incidence of hashimoto thyroiditis has been reported in patients with turner syndrome , but several cases of graves disease were also described ten to 20 years ago . we report the case of a patient with turner syndrome who developed graves disease , 3 years after successful treatment with recombinant human growth hormone ( gh ) . a diagnosis of graves disease was made and treatment with thiamazole was started , which resulted in normalization of the thyroid function . it is important to monitor thyroid function as well as growth parameters in patients with turner syndrome .

a 28-year - old healthy male was seen in our clinic complaining of vision loss in his right eye ( od ) . best - corrected visual acuity ( bcva ) was od : 20/200 and left eye ( os ) : 20/20 . mild vascular abnormalities were detected in the temporal aspect of right optic nerve , but no conclusive information was obtained . oct using the stratus oct 3 model ( carl zeiss meditec , jena , germany ) was indicated for the evaluation of the macular areas , rnfl thicknesses , and optic nerves . the fast macular protocol revealed subtle macular thickness beyond normal in the superior and nasal quadrants of both maculae . no visible alterations in the internal microarchitecture of the retina were observed using several retinal lines and optic disc protocols . a slight incremental thickening of the rnfl was observed in the superior and nasal quadrants of the os . in order to evaluate the patient 's visual field ( vf ) and retinal sensitivities , a frequency doubling technology perimetry ( fdt ) , using the commercially available ( matrix ) device , was performed in both eyes . the threshold 30 - 2 strategy revealed the presence of junctional scotoma composed by a central scotoma in od associated with superior temporal quadrantanopia in the fellow eye . the pattern detected in the vf suggested the presence of an expansive mass at the level of the optic chiasm [ fig . 1 ] . magnetic resonance imaging ( mri ) was performed which disclosed the presence of a tumor , compatible with the diagnosis of pituitary adenoma [ fig . 2 ] . after a complete neurological evaluation , medical treatment with cabergoline ( a dopamine agonist ) , after 8 months , a significant reduction of tumor volume was achieved . moreover , the patient experienced a full recovery of bcva and vf [ fig . 3 ] . right : superior temporal quadrantanopia in os central nervous system mri . left : pituitary dependent macroadenoma . visual loss associated with a junctional scotoma is a well - known clinical sign related with the presence of a compressive mass in the chiasmal area . monteiro described a generalized reduction of the rnfl thickness in the retinas of patients with band atrophy secondary to pituitary tumors . lederer and colleagues reported on the usefulness of the macular map thickness , while studying patients with glaucomatous optic nerve alterations . due to a relative incremental change in the ganglion cells axonal concentration within the macular area interestingly , the patient described here showed a thickening in the nasal and superior and nasal aspects of both maculae . this tomographic sign , not visible on the biomicroscopic fundus examination and in the fa , was interpreted as an early retinal manifestation produced by the presence of the tumor . the physiopathology of this localized , incremental thickness is merely speculative , but could be produced by an alteration in the axonal transport in ganglion cells . after obstruction of the axoplasmic flow , an early enlargement ( intracellular edema ) of the nerve fibers followed by a chronic atrophy could occur . though no direct evidence exists corroborating this phenomenon , at least three indirect clinical issues support this theory : ( 1 ) the retinal thickness increment was revealed anatomically by the oct , but no evidence of dye leakage was seen in the fa . ( 2 ) the presence of a topographic correlation between the junction scotoma and the macular thickening . ( 3 ) the visual loss was ipsilateral to the main tumor location . furthermore , the macular thickness enlargement was symmetric while the visual alteration was roughly asymmetric . this most likely could be indicative of the potential for intracellular edema preceding the visual function alteration and this thickening could be an early sign that could be detected before consolidated fiber atrophy occurs . frequency doubling technology perimetry ( matrix fdt ) has shown to be a suitable method for studying and detecting abnormalities in patients with neurological visual field deficits . during the functional evaluation of this patient , the fdt revealed the presence of a junctional scotoma compatible with the tumor location . even with an asymmetric vf defect , the oct was able to show symmetric involvement , with respect to macular thickness . we speculate that the anatomical alteration revealed by the oct precedes the functional deficit found in the vf . thus , we propose that detection of bi - superonasal macular edema ( me ) could be an early sign of chiasmal pathology . with an early diagnosis and subsequent treatment , a complete restoration of visual function was achieved in this case , stressing the importance of early recognition of the disease . we are unaware of previous reports regarding localized bi - superonasal me secondary to a pituitary adenoma and could find no references to it in the medical literature . studies including a cohort of patients are warranted for the evaluation of these tomographic findings . in conclusion , it is important to suspect pituitary adenoma in cases of vf deficit and oct macular alterations .

a 28-year - old healthy male complaining of vision loss in his right eye was discovered to have localized bi - nasal macular edema in the presence of a pituitary adenoma . the presence of a junctional scotoma composed by a central scotoma in the right eye associated with superior temporal quadrantanopia in the fellow eye was seen . the pattern detected in the visual field suggested the presence of an expansive mass at the level of the optic chiasm . optical coherence tomography findings also revealed subtle macular thickness beyond normal in the superior and nasal quadrants of both maculae . this report illustrates the importance of suspecting a pituitary adenoma in the light of uncharacteristic retinal alterations .

six species of echinococcus have been recognized , but four of them are of public health concern ( 1 ) . the greatest prevalence of hydatidosis in human and animal hosts is found in sheep - raising countries , including north america and south america , the entire australia , new zealand , europe , central asia , china , and parts of africa ( 1 , 2 , 46 ) . various parts of body may be involved with hydatid cyst but the liver and lungs are the main locations ( 7 ) . skeletal muscle infection is rare , and reported 0.5% 4.7% of all cases of echinococcosis ( 8) . patients with hydatid cyst are asymptomatic and present at an advanced stage of hydatidosis , when lesions have become extensive ( 7 ) . here we report a case of this rare entity of an isolated hydatid cyst of the muscle of the thigh . a 70-years old housewife living in ardoghesh , a village in neyshabur , northeast of iran , was admitted to general surgery clinic in feb 2014 because of a painless mass in the back of her left thigh . she had a history of removing hydatid cyst surgery in her left thigh from three years ago . laminated layers of hydatid cysts were observed and two round masses was successfully removed ( fig . hydatid cyst with laminated layer ( original ) gross pathology showed two soft cystic masses ( 134/54/5 cm and other 1744 cm in diameter ) that contained gelatinous material and multiple daughter cysts . in histopathologic examination cross section of a hydatid cyst with laminated layer and germinal layer , brood capsules containing multiple protoscolices , hooklets are considered as diagnostic keys ( h&e ) . pathological examination confirmed diagnosis as hydatid cyst of thigh ( fig . 2 , 3 ) . hydatid cyst in muscle ( original ) hydatid cyst in muscle showing germinal layer ( original ) hydatid disease is a very serious problem in sheep - raising countries caused by tapeworms belonging to the class cestoda , in the family taeniidae , of the genus echinococcus . they measure 3 mm to 6 mm long when mature and lives in intestine of carnivores , particularly dogs and other canines , as definitive hosts . many mammals may serve as intermediate hosts , but herbivorous species are most likely to become infected by eating eggs on contaminated herbal material . humans are seldom involved as accidental intermediate hosts in these cases and infected by accidentally ingestion of echinococcus spp . hydatidosis is a serious public health problem in some parts of the world ( 4 , 10 ) . khorasan province , located in the northeastern part of iran had the highest incidence rate for hydatidosis ( 11 ) . although the incidence of hydatidosis has decreased because of education and control programs , there are still concerns in some parts of the world ( 12 ) . hydatid cyst is most commonly found in the liver and lung , while they can occur in other organs including muscle , brain , eye , spleen , kidney , orbit , lymphatic glands , myocardium , tonsil , pancreas , skin , ovary , uterus and parotid glands ( 2 , 1317 ) . hydatidosis are usually asymptomatic until adolescence due to the slow growing process of the parasite in tissues such as muscle and bone , although it can be acquired at any age ( 18 ) . incidence rate of musculoskeletal hydatidosis is not clear . some reports showed an incidence of musculoskeletal echinococcosis including involvement of subcutaneous tissue as 0.5%4.7% among all cases of hydatid disease and soft - tissue hydatid cysts occur in 2.3% of cases reported from endemic areas ( 8 , 19 ) . muscles provide a poor environment for the parasite because of the presence of lactic acid and mechanical factors , such as contractile activity , may make encystment less likely ( 1820 ) . it may mimic any soft tissue tumor such as abscess , synovial cyst , and malignant tumor . before biopsy of cyst , diagnosis of hydatidosis should be confirmed to avoid leakage of cyst contents and the accompanying risks of anaphylaxis ( 20 ) . hydatidosis in soft tissues may present with a variety of patterns and recognizing them is necessary in diagnosis ( 18 ) . in our presented case , preoperative diagnosis was malignant neoplasm and after surgery , hydatidosis was confirmed . rokni yazdi et al . noted left thigh hydatidosis in a 50-years - old housewife living in a village in zanjan , northwestern iran ( 18 ) . noted left thigh hydatidosis in a 50-year - old woman from rural area around rasht city with no history of trauma , fever , or weight loss ( 20 ) . in conclusion , the hydatid cyst can present in any part of the body and no part is protected . the infestation may resemble a soft tissue tumor in the muscle and therefore in endemic area of hydatidosis , hydatid cyst should be considered as differential diagnosis of any soft tissue mass . in this case ,

hydatid cyst is an important endemic zoonosis in iran . it may be seen in various organs of body . musculoskeletal system is rarely involved by hydatid cyst , the larval form of echinococcus granulosus . on clinical basis , it may resemble any soft tissue tumor . a 70-years old housewife living in ardoghesh , a village in neyshabur , northeast iran , was admitted to general surgery clinic because of a painless mass in the back of her left thigh . this case emphasizes that hydatidosis should be included in differential diagnosis of any soft tissue mass especially in regions where hydatidosis is endemic .

reversal or shrinkage of early ischemic injury demonstrated by diffusion - weighted mri ( dwi ) is clinically uncommon , even after early thrombolytic reperfusion therapy [ 1 , 2 , 3 , 4 , 5 ] . the dwi - defined early ischemic injury physiologically represents an irreversible ischemic core and a potentially reversible surrounding area . recently , we experienced the case of a nearly complete reversal of a hyper - acute large ischemic injury on dwi . a 67-year - old previously healthy woman suddenly developed stupor and left hemiparesis , and arrived at our hospital 45 min after symptom onset . upon presentation , the national institute of heath stroke scale ( nihss ) score was 12 points , and baseline brain ct was perfectly normal . dwi ( single - shot echo - planar , b = 1,000 s / mm , tr = 8,000 ms , te = 80.8 ms , slice thickness = 6 mm ) performed on the 1.5 t mr scanner ( signa 1.5 t ; general electric , usa ) imaged 78 min after onset demonstrated a large high - signal intensity area in the right hemisphere with a dwi - aspects ( albert stroke program early computed tomography score ) of 5 points , and mr angiography ( mra ) showed an occlusion of the right middle cerebral artery trunk ( fig . perfusion mri was not performed . on the apparent diffusion coefficient ( adc ) map , the mean ratio of the adc value of ischemic to unaffected hemispheres was 0.86 ( range 0.780.92 ) within the five dwi - aspects - negative ischemic areas , and the mean adc ratio was 0.99 ( 0.981.00 ) within the remaining five dwi - aspects - positive non - ischemic areas . accordingly , the patient received intravenous thrombolysis with tissue plasminogen activator at a lower dose of 0.6 mg / kg alteplase on the japanese guideline . the state of health of the patient was improved , and the nihss score 24 h later was of 0 points with minor left - sided numbness . the second dwi ( b = 1,000 s / mm , tr = 5,000 ms , te = 55 ms , slice thickness = 5 mm ) performed on the 3 t mr scanner ( achieva 3 t ; phillips , the netherlands ) imaged 30 h later showed a nearly complete reversal of the large high - signal intensity area demonstrated by initial dwi , and there were very small high - signal intensity spots at the cortical surface ( fig . the mean adc ratio was 1.00 ( 0.991.02 ) within the five areas of the initial dwi - aspects - negative ischemic territory and 0.97 ( 0.881.01 ) within the remaining five initial dwi - aspects - positive non - ischemic areas . the systemic work - up including cardiac and hematological profiles revealed the presence of patent foramen ovale and venous thrombus in her leg , suggesting a paradoxical brain embolism as an etiological mechanism for this stroke . the patient received anticoagulation with warfarin for secondary prevention . at 3 months , clinical outcome was a modified rankin scale score of 0 , and only minor final infarction was localized at the cortical surface on the fluid - attenuated inversion recovery ( flair ) image ( tr = 11,000 ms , te = 125 ms , slice thickness = 5 mm ) ( fig . in this patient , after early thrombolytic reperfusion therapy , the initial dwi - defined large hemispheric ischemic injury showed nearly complete reversal on the follow - up dwi , and very small thrombus - fragmented ischemic areas after complete vessel recanalization were localized at the cortical surface of the terminal zone of the initially occluded middle cerebral artery . a limitation of this case study was the subtle low imaging quality of the hyper - acute dwi , due probably to body motion in acute confusion and to the simple acute stroke mri protocol to minimize scan time in the emergency setting . to assess the ischemic injury more accurately , an advanced 3-tesla mr scanner was utilized at the later scans , although a difference of mri scanner between hyper - acute and the later phases may affect the precise comparison of ischemic injury . since a recent study reported that standard 1.5-tesla mr scanner , rather than 3-tesla mr scanner , provided a lower false - positive and false - negative rate for detecting dwi - defined early ischemic injury within 6 h after stroke , hyper - acute dwi imaged on a 1.5-tesla mr scanner might have been an optimal selection as acute stroke mri protocol in this case study . the latest meta - analysis reported that the rate of complete or partial reversal of ischemic dwi lesions was surprisingly high by an average of 24% , varying from 0 to 83% probably due to the variable definition of the dwi reversibility . time of acute dwi scan from stroke onset , as well as time and type of sub - acute to chronic scans such as dwi , t2- or flair image to assess the final infarct area , may affect frequency and size of the dwi reversibility . true reversal of a dwi abnormality , defined by eliminating the false - positive reversal effect , was uncommon at only 7% in patients receiving early intravenous thrombolysis . in this patient , nearly complete reversal of the initial dwi - defined large ischemic injury persisted on the 3-month follow - up flair image . a previous study quantitatively measured severity or depth of ischemic injury by adc values to define the threshold of the infarct process . in the dwi - defined ischemic area , an adc value below 80% of the unaffected area and no reperfusion were the factors of dwi irreversibility , but the exact threshold of the adc value could not be determined . in this patient , an adc decline with an average of 86% in the dwi - defined ischemic area and early successful reperfusion may largely account for complete and sustained reversal , associated with a favorable clinical outcome . in conclusion , hyper - acute large ischemic injury demonstrated by dwi may very rarely represent a nearly perfect reversible area , and it may be a therapeutic target .

reversal of early ischemic injury on diffusion - weighted mri ( dwi ) occurs rarely . in a stroke patient who abruptly developed stupor and left hemiparesis , dwi scanned 78 min after onset demonstrated a large ischemic injury in the right hemisphere with a dwi - aspects ( albert stroke program early computed tomography score ) of 5 points , although baseline brain ct was perfectly normal . mr angiography ( mra ) showed an occlusion of the right middle cerebral artery trunk , and the patient received intravenous thrombolysis 105 min after onset . a second mra 30 h later showed complete vessel recanalization , and dwi demonstrated a perfect reversal of the initial large ischemic injury , associated with very small thrombus - fragmented cortical surface infarctions . outcome at 3 months was a modified rankin scale score of 0 , and the fluid - attenuated inversion recovery image showed only a small final infarction at the cortical surface . hyper - acute dwi - defined large ischemic injury may very rarely represent a nearly perfect reversible area , and it may be a therapeutic target .

a 47-year - old lady presented to us for evaluation of persistent hydroureteronephrosis on imaging . 3 months earlier , she had been treated at another center for a 3 month history of right colicky flank pain associated with malaise and fever , without any lower urinary tract symptoms . investigations at that time showed raised creatinine ( 4.8 mg / dl ) and bilateral hydroureteronephrosis on ultrasonography . she was treated with antibiotics for suspected pyelonephritis and serum creatinine showed a downward trend , reaching a nadir creatinine of 1.41 mg / dl over the next 3 months . her medical history was significant for diabetes for 8 years , hypothyroidism for 4 years and hypertension for 3 years . evaluation at our centre revealed 2 - 4 red blood cells and 6 - 8 white blood cells in the urine . computed tomography ( ct urography ) showed bilateral hydroureteronephrosis with global caliectasis , right and left ureter were dilated till s1 and l5 vertebral level respectively , at which point there was a hyperdense enhancing lesion within the ureteric lumen , associated with ureteric wall thickening , periureteric and retroperitoneal fat stranding and normal ureteric caliber below this level . she was planned for cystoscopy and bilateral retrograde pyelography but required emergency bilateral percutaneous nephrostomy for sudden onset anuria , breathlessness , azotemia ( serum creatinine 11.1 mg / dl ) , hypertensive crisis ( blood pressure 210/110 ) and flash pulmonary edema . she had post obstructive diuresis and the creatinine level reached a nadir of 1.53 mg% at 2 weeks . cystoscopy and retrograde pyelography revealed bilateral mid - ureteric narrowing [ figure 2 ] , which persisted on balloon dilatation . a ureteroscope could be negotiated till the lower level of narrowing on both sides and revealed mildly edematous urothelium ; no obvious luminal lesion was identified . intramural pathology compressing the ureteric lumen symmetrically on both sides was considered , and she was taken up for laparotomy and frozen section histology . venous phase of contrast - enhanced computed tomography of abdomen and pelvis showing : ( a ) bilateral global dilatation of calyces and pelvis , ( b and c ) red and blue arrows showing right and left ureters respectively , ( d ) showing normal urinary bladder retrograde pyelography done before ureteroscopy : ( a and b ) showing filling defect in right ureter at level of upper sacroiliac joint , both proximal and distal ureter are well opacified with radio contrast , ( c ) showing filling defect in left ureter , faint opacification of proximal ureter is seen at upper sacroiliac joint on laparotomy , the left ureter was found to be thickened and fibrotic from l5 to s1 vertebral level ; similarly , right ureter was thickened and necrotic from l5 to s3 level , retroperitoneal tissue around these ureters was grossly normal . frozen sections from the ureteric wall on both sides were reported as caseating granulomatous inflammation and later confirmed on routine histopathology . an ileal segment was used to replace the involved ureteric segments from l3 level to the bladder and she was started on 4 drug antitubercular therapy ( att ) , with which she showed clinical improvement ( absence of fever , malaise and flank pain ) . six months later , creatinine was 0.66 mg% and follow up ultrasound of abdomen 6 months and 18 months post surgery showed resolution of bilateral hydronephrosis . she was continued on att beyond 6 months as evaluation for headache revealed an intracranial right cavernous sinus lesion which was not amenable to biopsy and was presumed to be tubercular in etiology . bilateral synchronous mid - ureteric lesions are rare and may be congenital , or iatrogenic , following radiotherapy or aortic aneurysmal surgery . bilateral ureteric involvement with acute renal injury has been described due to radiation - induced mid- and lower ureteric strictures ; however , bilateral synchronous mid - ureteric tubercular strictures without obvious radiological renal or bladder involvement as a cause for acute renal injury has not been described in literature . urinary system involvement in tuberculosis is commonly unilateral , probably due to delayed reactivation of a solitary focus . ureteric involvement is considered secondary to renal involvement , with the vesicoureteric junction being the most commonly involved . tuberculosis usually involves the intramural part of the ureteric wall and is characterized by ureteric thickening and post contrast ureteric wall enhancement on contrast - enhanced computed tomography . bilateral involvement with renal failure is commonly seen after descending infection from one renal unit involving the bladder and subsequent contralateral unit damage due to vesicoureteric reflux and/or small capacity poorly compliant bladder . this case is unique in many respects and can not be easily explained by accepted theories on the etiopathogenesis of urinary tuberculosis . there was bilateral , synchronous involvement of the mid - ureter , which , according to existing literature , is the least commonly involved ureteric segment in urinary tb . this can only be explained by taking into account the following facts : bilateral pathological involvement of the urinary system via hematogenous route is not unusual ; in fact , a seminal study by medlar found bilateral pathological involvement to be the rule , rather than the exception and renal tuberculosis can be clinically silent . involvement of bilateral ureteric segments either by direct hematogenous spread or following bacilluria from an undetectable renal lesion and subsequent simultaneous activation can explain the findings of the case . the interaction between host immunity and pathogenicity decides the clinical presentation . at one end of spectrum is the activation of a single focus of tuberculosis even in the presence of multiple tubercular pathological foci and at the other end is disseminated tuberculosis where more than one tubercular foci become clinically apparent simultaneously . in the case described above , the simultaneous clinical activation of two pathological foci and later on presentation of an intracranial lesion suggests this patient 's immune response lay somewhere midway along the spectrum . the presence of caseating necrotizing granulomatous inflammation is almost always associated with tuberculosis and rarely with nocardiosis ( where granuloma formation is rare ) ; however , the clinical features ( no solid organ abscesses , response to att ) are not consistent with the latter . if tuberculosis had been entertained as a differential diagnosis , appropriate microbiological work up could have been initiated and if proven positive , the patient would have benefited from a 4 to 6 week course of anti - tubercular therapy prior to treatment for ureteric stricture , if it failed to resolve with medical therapy .

a young female presenting with right flank pain , fever , raised creatinine and bilateral hydronephrosis was treated with antibiotics elsewhere , with presumptive diagnosis of bilateral pyelonephritis . she had partial relief in symptoms and her creatinine level showed an improvement . three months later during evaluation at our center she had anuria , hypertensive crisis and pulmonary edema which were managed with emergency bilateral percutaneous nephrostomies . cross - sectional imaging and ureteroscopy suggested bilateral synchronous intramural mid - ureteric lesions as underlying pathology . histopathology of the ureteric segments during laparotomy revealed caseating granulomas suggestive of tuberculosis . this clinical presentation has not been previously described in urinary tuberculosis .

a 36-year - old man presented with sudden severe occipital headache , and neck stiffness in may 1999 . after several weeks , the headache subsided , however , blurred vision subsequently developed . t1-weighted ( 665/14/2 [ repetition time / echo time / excitation ] ) and t2-weighted ( 4200/99/2 ) mr images showed a large cystic mass with a small solid portion in the left temporal lobe ( figs . gd - dtpa enhanced t1-weighted images showed marked enhancement of a thick peripheral wall and solid portion ( fig . 1c ) . on diffusion - weighted mr images ( b value=1000 sec / mm , isotropic image ) , the mass was surgically excised , and histopathologic examination revealed a typical adamantinous craniopharyngioma with anastomosing epithelial islands and a palisaded layer of cells , as well as an area of keratinization and numerous calcifications ( fig . craniopharyngiomas are generally considered to be epithelial tumors arising from remnants of the craniopharyngeal duct , which connects the stomodeal ectoderm with the evaginated rathke 's pouch , which in turn forms the adenohypophysis ( 7 , 8) . this theory suggests that craniopharyngiomas can arise anywhere along the migration of rathke 's pouch , which extends from the vomer and the roof of the nasopharynx , through the midline sphenoid bone to the floor of the sella turcica . thus , craniopharyngiomas can potentially arise in unusual locations such as the nasopharynx ( 2 , 8) , sphenoid bone ( 9 ) , third ventricle ( 3 ) , and posterior fossa ( 10 ) . however , the above hypothesis does not explain the development of craniopharyngiomas either in the pineal gland ( 5 ) or the temporal lobe as in our case . there is no clear embryological reason for craniopharyngiomas to originate from the pineal gland or temporal lobe . ( 6 ) suggested that they might originate from totipotential or multipotential cells that reside in the pineal gland . however , metastasis has never been described in this benign neoplasm , and therefore we think that the former hypothesis is more reasonable than the latter . craniopharyngioma would not usually be included in the differential diagnosis of a temporal lobe mass . given the well - defined cystic mass with peripheral dense enhancement , our preoperative diagnosis was pilocytic astrocytoma . craniopharyngiomas can be classified into two histopathologically and clinically distinct subtypes ( i.e. adamantinous and squamous - papillary variants ) ( 8) . the adamantinous type consists of a predominantly cystic lobulated tumor , which is often observed in an intrasellar / suprasellar location in children . these cysts contain various amounts of cholesterol , triglycerides , methemoglobin , protein , desquamated epithelium , and watery fluid content . squamous - papillary craniopharyngioma , on the other hand , consists of a predominantly solid or mixed solid - cystic spherical tumor in a suprasellar location in adults . the solid tumor parts have an inhomogeneous but intense enhancement with small necrotic areas , and calcifications are rare . the combination of papillary and adamantinous tumor parts within the same neoplasm has been described in 15% of these tumors . in summary , although our case did not show any specific radiologic finding permitting the differentiation of craniopharyngioma , to the best of our knowledge , this is the first case of a craniopharyngioma originating in the temporal lobe . it does not appear to be embryologically derived from ectopic embryonic remnants of the craniopharyngeal duct .

herein , we report on an unusual case of craniopharyngioma arising in the temporal lobe with no prior history of surgery and with no connection to the craniopharyngeal duct . mr images showed a cystic tumor with a small solid portion . to the best of our knowledge , this is the first case of a craniopharyngioma occurring in the temporal lobe .

a 22-year - old female reported with complaints of multiple missing teeth in upper and lower anterior region . on examination , patients skin was dry and soft on face and increased thickness of nails ; palm and sole were normal . the patient had 18 , 15 , 12 , 22 , 27 , 28 , 38 , 45 , and 48 missing teeth with generalized microdontia . the canines had cone shaped clinical crowns , and molars appeared malformed [ figure 1 ] with obliterated occlusal tables . vertical dimensions were reduced due to a lack of occlusion and vertical stop causing protuberant lips . the panoramic radiograph confirmed presence of retained primary teeth in both the arches . with the above findings and orthopantomogram ( opg ) figure , we came to a conclusion and diagnosed as haed . to restore the missing teethto increase the vertical dimensionto correct size of teethalignment of teeth . to restore the missing teeth to increase the vertical dimension to correct size of teeth alignment of teeth . treatment plan included compensating microdontia by increasing tooth size using fpd retained by implant . to use implants , enough space was required ; so orthodontic alignment of teeth was required . as teeth were distributed unevenly , it had to be aligned to gain space for implants . retained deciduous teeth were extracted and orthodontic correction [ figure 2 ] done with aligning and leveling . orthopantomograph during orthodontic correction treatment two implants [ figure 3 ] were placed in region of 12 , 13 and one in the region of 45 . final fpd [ figure 4 ] was given and orthopantomograph [ figure 5 ] taken posttreatment . intraoral photograph posttreatment orthopantomograph posttreatment the prosthetic rehabilitation provides the patient with esthetic , functional , and phonetic benefits , as well as a better outlook towards her social life and peers oral hygiene instructions , were given to the patient , and he was asked to report for follow up and assessment of her fixed prosthetic appliance after 6 months . to restore the missing teethto increase the vertical dimensionto correct size of teethalignment of teeth . to restore the missing teeth to increase the vertical dimension to correct size of teeth alignment of teeth treatment plan included compensating microdontia by increasing tooth size using fpd retained by implant . to use implants , enough space was required ; so orthodontic alignment of teeth was required . as teeth were distributed unevenly , it had to be aligned to gain space for implants . retained deciduous teeth were extracted and orthodontic correction [ figure 2 ] done with aligning and leveling . orthopantomograph during orthodontic correction treatment two implants [ figure 3 ] were placed in region of 12 , 13 and one in the region of 45 . final fpd [ figure 4 ] was given and orthopantomograph [ figure 5 ] taken posttreatment . intraoral photograph posttreatment orthopantomograph posttreatment the prosthetic rehabilitation provides the patient with esthetic , functional , and phonetic benefits , as well as a better outlook towards her social life and peers oral hygiene instructions , were given to the patient , and he was asked to report for follow up and assessment of her fixed prosthetic appliance after 6 months . the typical treatment of a patient with ed is achieved in several phases , depending on the craniofacial development , thus requiring a comprehensive and multidisciplinary approach . the different treatment modalities are dictated by manifestation of level of hypodontia and resulting malocclusions . numerous clinical reports have demonstrated importance of prosthetic dental treatment in ed patients for psychological and psychosocial reasons . a number of reviews regarding treatment of ed has showed that implant therapy in early infancy or adolescent age while little information is present in literature for ed patient above 18 years of age . prosthodontic treatment of ed can include fixed , removable , or implant supported prosthesis of which implant and fixed partial prosthodontics are the most frequent modalities . in removable prosthesis , frequently the oral mucosa is dry due to a decrease in the number of mucous glands and lesser quantity of saliva which makes retention of removable prosthesis more difficult . overdentures can be used to restore ideal occlusion and usually allow preservation of existing dentition , but these require rigorous oral hygiene regimes to avoid development of caries and periodontal problems . this case report describes a routine method for fixed prosthodontic treatment of a patient with ed . as the patient was older than 18 years , the growth period was assumed to be over that would have resulted in the failure of fpds as shown by hogeboom . a study by guckes et al . , showed that patients younger than 18 years had a hazard ratio of 2.8 compared to the patients older than 18 years . so for young patients , fpds should be avoided as they could interfere with jaw growth and implants should be recommended and vice versa in patients > 18 years . the dental appearance of patients affected by ed has to be improved for physiologic and psychologic reasons , so that they can lead a normal social life with self - esteem . this clinical report demonstrates the implant retained fpd as a suitable treatment while treating an adult patient with ed . this treatment option gives excellent result , which not only improves masticatory function but also enhances esthetics , allowing patients to lead a normal social life .

ectodermal dysplasia represents a group of rare inherited conditions in which two or more ectodermally derived anatomical structures fail to develop . early dental intervention can improve patients appearance , thereby minimizing associated emotional and psychological problems in these patients . treatment requires a teamwork by medical personnel along with dental professionals of various specialties . here , a rare case of a young female patient is presented with prosthetic management with implant supported fixed partial denture .

the lingual tonsils develop at 6.5 weeks between the second and third arches ventrally while palatine tonsils develop at 8 weeks from second pouch ( ventral and dorsal ) . tonsils are predominantly b - organs and b - lymphocytes comprise 5060% of tonsillar lymphocytes . ample evidence shows that tonsils are involved in inducing secretory immunoglobulin production [ 4 , 5 ] . both adenoids and tonsils are favourably located to mediate immunologic protection of the upper aerodigestive tract as they are exposed to air borne antigens . tonsils are particularly designed for direct transport of foreign material from the exterior to the lymphoid cells . involution of the tonsils begins after puberty , resulting in a decrease of the b cell population and a relative increase in the ratio of t to b cells . the commonest indication for tonsillectomy is recurrent tonsillitis , which results in shedding the immunologically active cells and decreasing antigen transport function with subsequent replacement by stratified squamous epithelium [ 6 , 7 ] . we investigated the common pathogens causing this condition in our hospital and report here our findings . patients presenting at our clinic with signs and symptoms of chronic tonsillitis were enrolled for the study . the study was explained to them and where children were involved , to their parents . before the operation began , the laboratory was informed and a technician stood by to collect the tonsil as soon as it was removed . sterile wide - mouthed container was provided and the excised tonsils were aseptically put into them and carried immediately to the laboratory for processing . as soon as the tonsil reaches the laboratory , it is cut into two with a sterile surgical blade ; the inner surfaces were swabbed with sterile cotton swab , and inoculated onto two blood agar plates , one macconkey agar and one chocolate agar plate . one blood agar plate was incubated anaerobically , the chocolate plate in 510% co2 while the rest of the plates were incubated aerobically . the aerobic plates and the co2 plate were examined after 24 hours ; if no growth , they were reincubated for a further 24 hours after which if still no growth , they were discarded as negative . the anaerobic cultures were examined at 72 hours and if no growth they were reincubated for a total of 7 days . there were 34 bacterial isolates from 52 patients , giving a percentage positivity of 65.38% . thirty isolates were gram - positive bacteria and only four were gram - negative , made up of two genera , klebsiella and pseudomonas . staphylococcus aureus was the predominant isolate ( 15/34 , 44.1% ) , followed by group b streptococcus ( 12/34 , 35.3% ) . others were , streptococcus pyogenes ( group a streptococcus ) , 1/34 , 2.94% ; and untypable streptococcus spp . 2/34 , 5.88% . the gram - negative bacteria consist of klebsiella pneumoniae 3/34 , 8.82% and pseudomonas aeruginosa 1/34 , 2.94% ( table 1 ) . there were no growths in 7 patients while 11 yielded growth of normal flora only . all the cases were chronic and most of them took antibiotics before presenting to us . the ratio of anaerobic to aerobic bacteria in saliva is approximately 10 : 1 because of variations in oxygen concentration throughout the oral cavity . invargsson et al . revealed that streptococcus pneumoniae was recovered in 19% of healthy children , hemophilus influenzae in 13% , group a streptococcus in 5% , and moraxella ( branhamella ) catarrhalis in 36% . the frequency of pathogens decreases with age , possibly because of increased immunity . because the oropharynx is colonized by many organisms , most infections of wadeyer 's ring are polymicrobial . in our study , but in contrast with other researchers who found beta - hemolytic streptococci to be the predominant isolate [ 14 , 15 ] . these authors also found that streptococcus pyogenes was isolated more frequently in recurrent tonsillitis while in the tonsillar hypertrophy , streptococci beta - hemolytic non a group predominated . it has been suggested that fine - needle aspiration can be used in identifying tonsil core bacteriology in clinical settings . methicillin resistant staphylococcus aureus ( mrsa ) , has been isolated from the surface and core tonsils in children . we did not encounter any mrsa in our study ; and all the staphylococcus aureus isolated were sensitive to augmentin and vancomycin . it would appear from our results , that augmentin should be our drug of choice in future treatment of tonsillitis from this centre . the findings of kuhn et al . supported the etiologic role of hemophilus influenzae and staphylococcus aureus in hypertrophic tonsils with or without inflammation [ 18 , 19 ] .

objectives . tonsillitis is a common infection in all age groups , especially under the age of five . organisms causing this condition vary from place to place . our aim is to find out the main causative agents of this condition in our hospital . patients and methods . fifty - two consenting patients who needed tonsillectomy in khamis civil hospital , kingdom of saudi arabia , between september 2006 and april 2007 , were enrolled for the study . swabs were taken from their inner surfaces and cultured for anaerobes and aerobes according to standard microbiological techniques . results . fifty - two patients , consisting of 30 males and 22 females were enrolled . their mean age was 9.81 6.47 . nearly 65% of patients had positive cultures while 35% were negative . the commonest bacteria isolated were staphylococcus aureus ( 44.1% ) ; and group b streptococcus ( 35.3 % ) . two gram - negative bacteria , klebsiella pneumoniae , ( 8.82% ) , and pseudomonas aeruginosa ( 2.94 % ) , were also isolated . no anaerobe was isolated . conclusion . gram - positive cocci , consisting of staphylococcus aureus and group b streptococcus ( streptococcus agalactiae ) , are the major causes of tonsillitis requiring surgery in our hospital . antibiotic treatment of this condition should be directed largely against these organisms .

guillian barre syndrome ( gbs ) is associated in 45 - 75% of cases with cranial nerve involvement . facial nerve is the commonest to be involved followed by extra ocular muscles and lower cranial nerve involvement . only two cases has been reported till date with gbs with total paresis of motor cranial nerves . here a thirteen year old boy presented with acute progressive areflexic flaccid quadriparesis associated with motor cranial nerve involvement with bilateral facial and bulbar weakness . he had an upper respiratory infection one week preceding the motor weakness which started from the lower limbs . on day seven after the onset of motor weakness of limbs , the child developed significant bulbar weakness , difficulty in talking and could not move the tongue . he was totally anarthric . on day nine , he had significant respiratory muscle weakness requiring mechanical ventilatory support . on day fourteen , the nerve conduction studies ( ncs ) were suggestive of severe demyelinating motor sensory polyradiculoneuropathy . his anti - ganglioside antibody panel in the blood showed positive igm gm2 , gt1b , igg gm1,2,3 and gt1b antibodies . his csf showed albuminocytological dissociation and his antinuclear antibody was negative . his magnetic resonance image ( mri ) he was treated with intravenous immunoglobulin at a daily dose of 0.4 g / kg for five days . he showed gradual improvement and started swallowing after eight weeks of the onset of illness . the wasting of the tongue also improved gradually at 3 months after the onset of illness [ figure 2 ] . at 6 months repeat ncs was suggestive of motor sensory demyelinating radiculoneuropathy with improvement in conduction velocities and compound muscle action potential amplitudes compared to baseline study . tongue wasting noted at 2 weeks after the onset of motor weakness improvement in tongue weakness and wasting noted at 6 months twelfth nerve involvement , either isolated or as a part of multiple cranial nerve involvement is quite uncommon and only two cases has been reported till date as a part of multiple motor cranial nerve involvement in a case of gbs . , reported a case of fulminant gbs with quadriplegia and total paresis of motor cranial nerves and polo et al . , reported a case of atypical gbs with multiple cranial neuropathies including xii cranial nerve involvement twelfth nerve involvement , either isolated or as a part of multiple cranial nerve involvement is quite uncommon and only two cases has been reported till date as a part of multiple motor cranial nerve involvement in a case of gbs . , reported a case of fulminant gbs with quadriplegia and total paresis of motor cranial nerves and polo et al . , reported a case of atypical gbs with multiple cranial neuropathies including xii cranial nerve involvement gbs with multiple cranial nerve involvement is a known entity but the involvement of xii cranial nerve is extremely rare . our patient had multiple cranial neuropathies with involvement of vii , ix , x and xii nerves . he had a severe form of gbs with areflexic quadriparesis along with respiratory muscle involvement requiring prolonged ventilatory support . his mri brain was normal supporting that the tongue weakness is due to xii cranial nerve involvement . twelfth nerve involvement , either isolated or as a part of multiple cranial nerve involvement is quite uncommon and only two cases has been reported till date as a part of multiple motor cranial nerve involvement in a case of gbs . tan et al . , reported a fulminant case of gbs with quadriparesis with all motor cranial nerve involvement and their ncs showed segmental demyelination which was responsible for such severe involvement and possibly the pathophysiology in this case and our case are similar . described a 23 years gentleman who developed a progressive illness over ten days with diplopia , facial diplegia and a nasal voice . subsequently , the patient also developed weakness of the neck and tongue muscles , dysphagia , abolition of reflexes of the left arm and right triceps but without involvement of the respiratory muscles or other limbs . however , the same patient had involvement of reflexes of left arm and right triceps only without involvement of respiratory muscles and lower limbs . hence it was thought to an atypical variant of gbs in contrast to our case where he had all the typical features of gbs . our patient showed anti - gm2 antibody positive which is usually seen in post cmv infection with or without gbs . usually going on to ventilatory support requirement and the same is found in our patient . the two previous case reports did not have the autoantibody levels to corroborate the clinical and electrophysiological findings . the cranial neuropathy in our patient showed gradual recovery and tongue atrophy recovered over next three months . at 6 months gbs with multiple cranial nerve involvement can rarely involve the xii nerve as well causing significant tongue weakness and such a presentation may be indicative of a severe nature of the disease and it usually recovers over a period of time .

guillian barre syndrome ( gbs ) is associated with cranial nerve involvement . commonest cranial nerves involved were the facial and bulbar ( ixth and xth ) . involvement of twelfth cranial nerve is rare in gbs . we present a case of gbs in a thirteen years old boy who developed severe tongue weakness and wasting at two weeks after the onset of gbs . the wasting and weakness of tongue improved at three months of follow up . brief review of the literature about xiith cranial nerve involvement in gbs is discussed .

hyperparathyroidism ( hpt ) occurs when there is an abnormal increase in parathyroid hormone ( pth ) production by the parathyroid gland [ 13 ] . primary hpt ( phpt ) is caused by parathyroid adenomas in 85% of cases , leading to hyperplasia and over - secretion of pth . in most individuals in western society , it is diagnosed at an asymptomatic stage , without signs or symptoms of ( pth ) calcium excess . initial symptoms are nonspecific , such as weakness , malaise , fatigue and possible mood disturbances . if not diagnosed and left untreated , it leads to devastating consequences including nephrolithiasis , nephrocalcinosis , renal failure , osteopenia and osteoporosis . a 22-year - old male student presented to our hospital with a 2-year history of progressive lower extremity weakness . one year prior to the admission , he had been seen at another medical clinic because of fatigue and difficulty walking . his radiographs showed no fractures , and he was referred to physiotherapy for muscle strengthening . further questioning revealed that , despite physiotherapy , his weakness had progressed and he had to quit school as he was having considerable difficulty walking up a flight of stairs . a thorough investigation was performed and showed a serum calcium level of 3.46 mmol / l ( normal : 2.12.6 mmol / l ) and a pth level of 138 pmol / l ( normal : 1.69.3 pmol / l ) . he was referred to our general surgery service where he was admitted for excision of the parathyroid adenoma . upon admission , one day prior to the scheduled parathyroidectomy , he had a simple , low - energy fall while he was walking on his own to the hospital . radiographs revealed a displaced subcapital fracture of his left hip , a segmental fracture of his right humerus and extreme osteopenia ( fig . 1 ) . figure 1:(a ) left femoral neck displaced subcapital fracture and ( b ) right humeral shaft segmental fracture . ( a ) left femoral neck displaced subcapital fracture and ( b ) right humeral shaft segmental fracture . one day after sustaining this injury , the patient underwent an uncemented left total hip arthroplasty ( tha ) ( fig . 2 ) , and acetabular fixation was supplemented with multiple screws , and he maintained touch - down weight bearing for 6 weeks postoperatively . postoperatively , the pth level had decreased to 4.9 pmol / l , and the calcium level had returned to normal at 2.42 mmol / l . the calcium level continued to fall , and 2 weeks after the parathyroidectomy , it had reached 1.70 mmol / l . after a further 20 days , it started to normalize and then continued to remain stable , as shown in fig . 3 . figure 2:(a ) left thr and ( b ) right humerus in a brace . ( a ) left thr and ( b ) right humerus in a brace . a graph for calcium level from admission to 7 weeks after surgery we report this case to illustrate the importance of early detection and diagnosis of phpt , which was possible in this young and presumed healthy individual if proper assessment and management were done . furthermore , sending him for physiotherapy without a clear diagnosis increased the likelihood of missing the diagnosis and progression of the disease . solitary parathyroid adenoma is the most common cause of phpt , representing 8590% of cases . symptomatic phpt with skeletal , renal , abdominal and neuro - psychiatric manifestations has become exceedingly rare in developed countries . our patient was unusual in that he was not diagnosed early and presented with skeletal manifestations resulting in multiple fractures including femoral neck fracture ( fnf ) , which was treated with total hip replacement ( thr ) . at this young age , thr would affect his lifestyle and put him at risk of revision surgery early in his life . the literature clearly shows that the earlier hpt is detected , the more reversible the disease . we believe that , despite the young age of our patient , thr was still the preferred treatment in this situation owing to his poor bone quality , which could have led to failure of fixation ; in addition , severe fracture displacement carries a high risk of femoral head avascular necrosis . yang et al . found that salvage tha for failed internal fixation following fnf is a more technically demanding procedure with prolonged operative time and larger amounts of postoperative drainage ( within 24 h ) and that patients are at increased risk of developing hip complications compared with primary thr for acute displaced fnf . french et al . reported a case of a 21-year - old male with parathyroid adenoma who had presented with a left femoral shaft fracture and right fnfs . although these were treated with fixations , the right side required conversion to thr within a year of his presentation .

we present the case of a 22-year - old male with longstanding progressive fatigue , weakness and pain around his hips due to an undiagnosed parathyroid adenoma . the resultant primary hyperparathyroidism ultimately caused pathologic fractures . he was admitted to the hospital for further assessment and excision of the parathyroid adenoma . a few days after admission , he fell down while walking and was referred to our team . x - rays showed a displaced left femoral neck fracture ( fnf ) and right humeral shaft fracture with poor bone quality . his humeral fracture was treated conservatively , and the fnf was treated with total hip replacement . three days later , he underwent parathyroidectomy . this case demonstrates the importance of a thorough investigation of progressive weakness even in a young individual and illustrates the importance of early diagnosis of parathyroid adenoma to avoid the devastating end results of this condition .

socio - cultural factors are important in the epidemiology and psychopathology of various psychiatric disorders12 including factitious ones . they have an influence on the pathways to seeking medical help.3 in addition , illness behavior has cultural overtones in arab patients.4 factitious disorders are characterized by physical , and psychological signs or symptoms that are intentionally produced with no external incentives to feign illness.5 these disorders have been reported from various cultures.67 a distinction should be made between factitious disorders and malingering . in the latter , the patient produces symptoms with an obvious goal . in factitious disorders , the motivation to be a patient is vague and obscure . munchausen 's syndrome , in its classic description , is an uncommon subtype of factitious disorder which has received great attention.78 this syndrome is the earliest description of a factitious disorder with predominantly physical signs and symptoms . although factitious disorders are common among males , recent reviews indicated a preponderance of female patients.9 the probable judgement that a particular symptom is produced intentionally is made both by direct evidence and with the exclusion of other causes of the symptoms . almost in all reported cases of factitious disorders with physical symptoms , however , many such patients have been described as having underlying masochistic , borderline or dependent personality traits.9 although the prognosis is usually poor , patients who have adequate psychosocial support with less severe personality pathology can do better . in this article , a 45-year - old , illiterate , saudi housewife was referred from a medical ward for psychiatric consultation . during her stay in the medical ward , she was investigated for skin lesions distributed mainly on the abdomen and both thighs , but not on her back or other areas of the body inaccessible to the hand . her case history revealed that two years prior to her current psychiatric consultation , she was hospitalized for vague abdominal pain , but all investigations were normal . after discharge from the hospital , she consulted a traditional healer who treated her by cauterization . during the following two years , she presented with recurrent skin lesions on the abdomen , arms and both thighs . her illness had created marital discord but there was no family history of mental illness . the examination of the mental state did not show any major disorder . during her stay in the psychiatric ward for observation , evidence of intentional production of skin lesions on healed sites and on new areas was reported . when confronted with evidence of their factitious nature , she denied doing herself any harm . the judgement that the skin lesions were produced intentionally was made by direct evidence from the staff in the ward and by excluding other causes of these lesions . she was discharged from the psychiatric ward after three months and given a follow - up appointment in the psychiatric clinic but she never showed up . a 39-year - old , single , illiterate and unemployed saudi male presented with dramatic severe abdominal pain . he was vague and inconsistent when questioned in detail about the nature of the pain . when all of the investigations proved negative , he started to complain of chest pain . his past history showed that he had been admitted to different general hospitals in saudi arabia , some of which were far from his hometown . the information received from some of these hospitals showed that repeated medical and surgical consultations , including extensive investigations , did not reveal any physical disorder . in addition , psychiatric assessment showed no evidence of mental disorders either . during his stay in the psychiatric unit , he presented with acute renal pain , hematuria and evidence of self - induced blood tinged stool . on confronting the patient about the factitious nature of his complaints after organic causes had been ruled out , he became angry and discharged himself . two months later , he presented to the hospital in a deaf - mute state but left the hospital when again confronted . similarly , he did not benefit from traditional healers whom he had visited many times , on the advice of his relatives . one of the essential clinical features of the above two cases is the intentional production of physical symptoms . the first case is that of factitious dermatosis , the second is of chronic physical symptoms associated with multiple hospitalizations . the first case of dermatitis artefacta was preceded by cauterization from a traditional healer which might have acted as a predisposing factor . the second case is similar in presentation to other classic cases of munchausen 's syndrome10 described in several cultures . it is important for clinicians to remember that with factitious disorder there could be some real physical illnesses that need appropriate management.11 the behavior of these two patients has cultural dimensions . to travel , females in the saudi culture need mahram ( a person whom they can not legally marry ) who might not always be available.12 this requirement restricts their travel creates an important feature of what was known as wandering type of munchausen 's syndrome.13 in females , the type of munchausen 's syndrome that is characterized by less severe psychopathology , a higher functioning level and less frequent factitious behavior is classified as non - prototypical.14 this classification seems to be justified as revealed in case 1 , though it has recently been criticized8 because the criteria for classification are not applicable in a good number of factitious disorder cases . new modern hospitals are common in saudi arabia . for submissive female and male patients , falling sick this might be incorporated into the psychopathology of factitious disorders in saudi culture . in spite of socio - cultural factors , it is clear that doctors awareness and acceptance of the possibility of factitious disorders is a prerequisite to making the diagnosis . once factitious disorder is diagnosed , it is important to confront the patient but remain supportive . confrontation should be carefully planned . in saudi culture , it would be inappropriate to inform the relatives that the patient is feigning the symptoms , since this may precipitate psychotic breakdown of the patient . interestingly , both patients consulted traditional healers during their factitious behavior . although consulting traditional healers could be explained partially by the religious background of the saudi culture , it is interesting that in spite of the modern treatment available in saudi arabia , patients including those with factitious disorder , still consult traditional healers with their somatic and psychological symptoms .

factitious disorders are characterized by physical or psychological manifestations that are intentionally produced or feigned with no apparent external incentives in order to assume the sick role . these disorders are rarely reported or may be under - reported in saudi patients . we describe here two male and female saudi cases of such disorders . both presented predominantly with features of munchausen 's syndrome . like most psychiatric patients both had sought help from traditional healers prior to their reporting to the hospitals . inspite of the socio - cultural factors , it is clear that doctors awareness and acceptance of the possibility of factitious disorders is a prerequisite to making the diagnosis .