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sjgren 's syndrome ( ss ) is a chronic inflammatory autoimmune disease characterized by progressive lymphocytic infiltration of the exocrine glands and other extra - glandular structures . dryness of the eyes ( xerophthalmia leading to keratoconjunctivitis sicca ) and mouth ( xerostomia ) constitute the typical clinical condition of this syndrome . although patients with ss have a lifespan not significantly different from that of the normal population , these patients carry a greater risk of developing lymphoproliferative malignancy . in addition , other organ malignancies can also occur in patients with ss such as lung , breast , gastrointestinal , gynecological , renal , and skin cancers . considering all these , the diagnosis of breast cancer in patients with ss can be mistaken as cancer at an advanced stage particularly in the presence of axillary multiple lymph nodes . in this study , we report a very rare case of breast cancer associated with ss in which the cancer was overstaged and , thus , overtreated on the assumption of clinically positive axillary lymph node status . a 45-year - old woman with a 12-year history of ss presented with a complaint of a breast mass . a breast examination revealed a palpable mass , measuring 10 cm in diameter , located in the upper lateral quadrant of the right breast and right axillary multiple lymph nodes . on ultrasonography , the mass was a 4 cm solid lesion located in heterogeneous breast parenchyma , and conglomerates of multiple axillary lymphadenopathy suspicious of malignancy were also detected ( figure 1 ) . the mammography was almost normal due to the dense parenchymal pattern , except for the presence of the axillary lymphadenopathy ( figure 2 ) . a core - needle biopsy was performed on the breast lesion , and the diagnosis of ductal carcinoma in situ ( dcis ) was made preoperatively . based on the clinical suspicion of an advanced - stage breast cancer , the patient underwent a modified radical mastectomy . on postoperative histopathological assessment , the diagnosis of 8-cm high - grade dcis was established , however no axillary lymph node metastases were detected ( figure 3 ) . ss is an autoimmune disease that causes chronic inflammation and primarily affects the exocrine glands . because it is a systemic disease , ss can also exhibit a wide range of clinical manifestations . among these , benign or malignant lymphoproliferation due to infiltration by lymphocytes and plasma cells may be a prominent part of this syndrome . several studies have shown a high incidence of malignancy in ss , the most common being lymphoma . other non - lymphoid cancers including breast cancer can also occur in patients with this syndrome ; however , an increase in the incidence of these cancers has not been demonstrated . lazarus et al . reported on a retrospective cohort study of 112 patients with ss in whom 25 developed malignancies , including three cases of breast cancer . in a recent study reported by zhang et al . , malignancy was detected in 29 ( 2.2% ) of 1,320 patients with ss , including four patients with breast cancer . the preoperative diagnosis of breast cancer in the presented patient with ss was established by radiological evaluation followed by breast biopsy . lesion morphology , mammary gland density , and the lack of imaging technique skills may limit the sensitivity for detecting breast cancer . as such , mammography may not demonstrate up to 20 - 30% of malignancies in a dense breast pattern , as we encountered in the present case . although the incidence of axillary metastases in patients with dcis is small , the evidence of axillary lymph node conglomerates on both physical and radiological examinations in this case led us to a clinical impression of a metastatic or " n2 " disease in the tnm staging definition , and that is why axillary dissection , in addition to a mastectomy , was performed . we reviewed the literature and did not find any report regarding the management of such patients with ss presenting with breast cancer and an axillary clinicopathological discrepancy . we recommend that lymph node status be verified either pre- or intra - operatively by lymph node biopsy using either fine - needle , core - needle , or frozen - section procedures before establishing a definitive diagnosis and appropriate surgical treatment . in conclusion , clinicians should remain vigilant to the possibility of overstaged breast cancer due to the false clinical impression of axillary metastasis in patients with ss presenting with breast cancer . therefore , axillary node status should be verified first to correctly establish tumor stage in this very rare clinical situation .

sjgren 's syndrome ( ss ) is an autoimmune disease that chronic inflammation and lymph node proliferation . patients with ss carry a greater risk of developing lymphoproliferative malignancy . in addition to other organ cancers , breast cancer may also occur in these patients . considering these , breast cancer in patients with ss can be misdiagnosed as being in an advanced stage particularly in the presence of axillary lymphadenopathy . here , we report a rare case of a 45-year - old woman with ss who presented with a breast mass . radiology showed a 4 cm solid lesion and conglomerates of axillary lymphadonepathy . a breast biopsy revealed ductal carcinoma in situ . a modified radical mastectomy was performed ; however , no axillary metastases were detected . clinicians should remain vigilant to the possibility that a false clinical impression of axillary metastasis may occur in such patients with breast cancer . therefore , axillary node status should be verified first .

helicobacter pylori ( h. pylori ) is one of the most important factors in the gastroduodenal diseases . the infection is most commonly acquired in early childhood and leads to chronic gastritis in both children and adults and is the leading cause of peptic ulcer disease in humans [ 14 ] . it is a challenging matter for many physicians due to lack of knowledge about its life cycle and low rate of bacterial eradication . h. pylori has been shown to play a major role in the pathogenesis of gastric atrophy , chronic diarrhea , and growth retardation in children , intestinal metaplasia , dysplasia , and the development of gastric carcinoma and lymphoma subsequently [ 57 ] . besides , some benefits are also noted such as reducing prevalence of esophageal adenocarcinoma by decreasing the periods of gastroesophageal reflux disease . fecal - oral or oral - oral routes are the main candidate ways of its transmission , although much is unknown in this regard . gastroenteritis is another important disease in children caused by a variety of bacterial and viral agents and the exact responsible organisms are different from one area to another but generally , e. coli , shigella , and salmonella are the most common enteric bacterial pathogens [ 10 , 11 ] . recently , there are arising theories of protective effect of h. pylori infection on diarrheal diseases , showing the low prevalence of diarrhea in children infected by h. pylori [ 1214 ] , although there is still a living debate about it . on the other hand , it has been shown that h. pylori infection is associated with vibrio cholerae and salmonella infection possibly through hypochlorhydria resulting from acute or chronic h. pylori infection [ 9 , 14 ] . as salmonella and shigella entritis and also h. pylori infection are common gastrointestinal problems in children , especially in developing and underdeveloped countries , we designed this study to investigate the association between h. pylori infection and this bacterial gastroenteritis in children . the study is a case control study performed during 20092011 in the children medical center hospital , the major children 's hospital of iran affiliated to tehran university of medical sciences , tehran , iran . two matched groups were studied as follows : ( 1 ) group of children with acute bacterial gastroenteritis due to salmonella or shigella consisted of 122 consecutive children ( 55 females and 67 males ) , aged 2472 months old , 68 with shigellosis and 54 with salmonellosis ; ( 2 ) control group consisted of two hundred and four healthy children ( 100 males and 104 females ) with no history of diarrhea and no bacterial growth in their stool cultures . healthy children with history of diarrhea within 2 weeks before sampling and any child in each group with history of antibiotic therapy within 4 weeks prior to stool collection were excluded from study . none of the participants were treated with a proton - pump inhibitor or bismuth preparations . personal data including age ( 13 years and 36 years ) , gender , and address was also obtained from parents using a structured questionnaire . cases were from urban area but parents defer to get information about the exact socioeconomic level but as the hospital is governmental and located in the middle part of the city and the admitted children were from nearby areas , one can conclude that cases belonged to medium socioeconomic level . solid and semisolid stool specimens were tested for h. pylori antigen by the ga generic assays gmbh kit , h. pylori sandwich enzyme immunoassay ( germany ) , in accordance with the manufacturer 's instructions . in summary frozen specimens were immediately thawed and 100 mg ( 2 - 3 mm in diameter of a solid specimen ) of feces was suspended thoroughly . then the specimens were treated with anti - h . pylori antibody ( antibiotin conjugate ) and incubated at room temperature for 60 minutes . after washing , streptavidin - hrp conjugate ( included in the kit ) was added and the solution was incubated for 30 min at room temperature , then substrate f ( included in the kit ) was added , and after 15 min of incubation stop solution was added and finally the od was read at 450 nm and interpreted according to the manufacturer 's guideline . bacteria from stool samples were cultivated on eight different selective agar plates in order to isolate the microorganisms . macconkey agar was used for the detection of e. coli , salmonella , and shigella species . thiosulfate - citrate - bile salts - sucrose ( tcbs ) agar was used for the detection of vibrio species , mannitol - malt agar ( msa ) for staphylococcus aureus , and ss and xld for shigella and salmonella . the growth pattern of each organism on the specific agar including color and also biochemical tests were also used for organism detection . numerical data were evaluated using analysis of variance , followed by tukey 's post hoc test . among 112 patients enrolled in this study , 68 had shigella infection and 54 had salmonella infection . the prevalence of h. pylori infection in control group was significantly higher than in acute bacterial diarrhea group ( p = 0.007 ) , in which two of fifty - four cases of samonella infection and three of sixty - eight cases of shigellosis were infected by h. pylori while 27 out of 204 control children were infected . the risk of positive h. pylori infection in control group was 3.6 ( odds ratio = 3.6 , 95% ci : 1.339.5 , p = 0.007 ) times higher than bacterial infection group ( table 1 ) . there was no statistical difference in prevalence of h. pylori infection in variable age groups in control versus patients groups ( data not shown ) . diarrheal disease is recognized as a globally burdensome disease , associated with considerable children 's mortality and morbidity specifically in developing countries where most of the complications occur and can cause up to three million deaths per year [ 3 , 15 , 16 ] . the cause of diarrhea differs from one country to another and generally one can expect higher rates of bacterial infections in underdeveloped and developing countries in comparison with developed countries . several pathogenic microorganisms are incriminated as the etiologic agents of acute diarrhea such as rotavirus , adenoviruses , caliciviruses , and astroviruses , salmonella , shigella , enteropathogenic and enterotoxigenic e. coli ( epec and etec , resp . ) , aeromonas , plesiomonas spp . campylobacter jejuni , yersinia enterocolitica , vibrio cholerae , protozoa , and helminthes [ 17 , 18 ] . gastroenteritis , especially bacterial gastroenteritis , mostly occurs in developing areas where h. pylori infection is more prevalent and it has been proposed that there may be a common rout for both h. pylori and shigella transmission by houseflies . previous studies have shown conflicting results on association of h. pylori infection with other gastrointestinal pathogens [ 3 , 7 , 9 , 14 ] . in this study we evaluated the h. pylori status in children with gastroenteritis and compared it with normal controls . we focused on shigella and salmonella as they are the most frequent isolates from stool cultures of children in our area . our results revealed that the prevalence of h. pylori infection in healthy children was higher than in patients with bacterial diarrhea indicating that bacterial infected patients are less infected with h. pylori . these findings are in line with other studies showing protective role of h. pylori infection and reporting a reduced frequency of diarrheal illness in h. pylori infected children [ 12 , 14 ] . it can be due to either increase in gastric acid production in individuals infected by h. pylori which leads to bacterial pathogens damage or activation of immune system as a result of h. pylori infection and increased iga production , which is fatal for enteric pathogens [ 2023 ] . as a matter of fact , gastric acid and peptides are necessary for activation of some enteric pathogens especially that viruses and h. pylori infection can disrupt this process [ 2427 ] . previous studies have shown that children 's response to h. pylori infection is more severe than adults so this observation may be in part due to the natural response of immune system of children . contradictorily , some studies have shown h. pylori infection to be a risk factor of some bacterial gastroenteritis [ 28 , 29 ] . according to the fact that the pathogenesis and etiology of h. pylori infection are not fully understood and there are very few studies considering the relation between h. pylori infection and other bacterial pathogens causing gastroenteritis , further investigations , considering different aspects including h. pylori life cycle , products , and cytotoxins are needed . considering lack of correlation between prevalence of h. pylori infection and gender or age , it can be suggested that the difference in h. pylori prevalence in the two examined groups would be due to the organism itself . our study has some limitations , such as having rather small number of enrolled patients in this study which may to some extent weaken our results . parenthetically , it should be mentioned that the specificity and sensitivity of the used kit were 100% and 91% , respectively , according to its manual . in the literature review , we found some conflicting data about this test but many of the articles indicated it as a good alternative in children [ 3034 ] . there are different complications in h. pylori infection such as gastritis , gastric lymphoma , and carcinoma , but in contrast h. pylori infection decreases the risk of esophageal adenocarcinoma [ 6 , 35 , 36 ] . there are many studies showing association or protective role of h. pylori infection in different disease groups , for example , reducing barrett 's esophagitis , decreasing risk of esophageal cancer , decreasing risk of gastric cardiac cancer , or decreasing the bleeding risk of esophageal varices in cirrhotic patients . according to our findings , h. pylori infection may be candidate agent which plays a protective role in gastroenteritis in children . so it is important to consider all of the positive and negative aspects of h. pylori infection before its eradication ; however , because of the current debate and considering the fact that knowledge about h. pylori life cycle and its pathogenesis is not explicitly defined more comprehensive research is recommended . searching for viral gastroenteritis and determining the cag a status of h. pylori by means of pcr method are also suggested .

background . h. pylori infection leads to chronic gastritis in both children and adults . but recently , there are arising theories of its protective effect in diarrheal diseases . aim . to explore the prevalence of h. pylori infection in children with bacterial diarrhea and compare it with healthy controls . patients and methods . two matched groups consisted of 122 consecutive children , aged 2472 months old , with acute bacterial diarrhea , who had shigellosis ( n = 68 ) and salmonellosis ( n = 54 ) as patients group and 204 healthy asymptomatic children as control group enrolled in this study . results . the prevalence of h. pylori infection in healthy control children was significantly higher than in patients group , ( odds ratio = 3.6 , 95% ci : 1.339.5 , p = 0.007 ) . in our study , only 2/54 salmonella infected patients and 3/68 of shigellosis had evidence of h. pylori infection , while normal control children had 27/204 infected individuals . conclusion . h. pylori infection may play a protective role against bacterial diarrhea in children . so it is important to consider all of the positive and negative aspects of h. pylori infection before its eradication .

endovascular aneurysm repair ( evar ) is now well established as treatment option for abdominal aortic aneurysms ( aaa ) . up to 70% of all infrarenal aaas like all other surgical procedures that involve the implantation of non - degradable prosthesis , stent - graft infection is a dreaded complication , but it is fortunately rare . although there is no convincing evidence , it is generally accepted that the incidence of aortic graft infection is higher with open repair ( or ) than with evar . once established infected aortic grafts can lead to bacteraemia , para - aortic abscesses , psoas abscess and aorto - enteric fistulae . a variety of reconstruction options are available to re - establish arterial flow to the pelvis and lower limbs . we report a case in which an otherwise uneventful evar was complicated a month later by development of a psoas abscess . we discuss our management strategy and review other management options as detailed in the literature . an 82 year old gentleman with known peripheral vascular disease and previous open popliteal aneurysm repair underwent endovascular repair of a 58 mm infrarenal abdominal aortic aneurysm ( fig . 1 ) using a cook zenith bifurcated prosthesis the zenith flex aaa endovascular graft ( cook medical inc . , bloomington , usa ) . the operation , which was performed under general anaesthetic and bilateral groin cut downs with intravenous prophylactic antibiotic cover on induction ( co - amoxiclav 1.2 g ) was uneventful . completion angiograms showed satisfactory exclusion of the aneurysm sac with good graft position and no endoleaks . post operatively the patient had a brief period of low grade pyrexia and lower abdominal pain that settled spontaneously . an 82 year old male with 5.8 cm aaa of 10.5 cm in length four weeks following discharge the patient was re - admitted with feeling increasingly unwell , recurrent pyrexia , loss of appetite and mild shortness of breath on exertion . blood tests on admission showed hb 11.4 g / dl ( 11.5 - 16.0 g / dl ) , white cell count 13.1109/l ( 4 - 9.2 x 109/l ) and crp 68mg / l ( <3 mg 2,3 ) showed a 50 mm maximum retroperitoneal collection situated between the right kidney and the right iliac vessels . ct guided drainage was carried out using a 10 french gauge pigtail catheter locked pigtail ( meditech flexima regular all - purpose drainage catheter sets with locking pigtail ( boston scientific ) ) ( fig . the isolation of e. coli from the collection with negative hemocultures suggested a bowel source for the infection but no actual breach was demonstrable . a 50 mm maximum retroperitoneal collection situated between the right kidney and the right iliac vessels a 50 mm maximum retroperitoneal collection situated between the right kidney and the right iliac vessels the patient 's condition improved quite rapidly and the intravenous antibiotics were stopped and replaced with oral ciprofloxacin upon microbiological advice ( for a total of six weeks ) . the drain was removed after 2 weeks when the series of repeat ct scans showed the abscess had nearly completely resolved ( fig . further cts on follow up at 6 weeks and 3 months post discharge show no collection at all . at the last clinic visit ct guided drainage was carried out using a 10 french gauge pigtail catheter locked pigtail ( meditech flexima regular all - purpose drainage catheter sets with locking pigtail ( boston scientific ) ) near complete resolution of psoas collection after 2 weeks of intravenous antibiotics aortic endograft infection ( aei ) is fortunately rare , 0.1% according to the euro registry . this rate is much lower than rates for open abdominal aortic aneurysm repairs ( 0.4 0.7% ) ( 2 ) . re - interventions , emergency presentation and endoleaks appear to increase the incidence of graft sepsis . it is not known whether mode of access i.e. femoral cut down vs. percutaneous access has any effect on infection rates . there have been a few reports of psoas abscess collections complicating aortic stent graft placement in the literature . recurrent fever , general unwellness and haematological signs of sepsis in a post op evar patient should arouse suspicion . ct scanning is usually diagnostic but white cell scintigraphy or pet scans may be required . repeated blood cultures are often necessary to identify the responsible pathogen . sharif et al reported 2 cases of psoas abscesses amongst 6 cases of aei out of 509 evar cases over an 8-year period ( 3 ) . both required open surgical graft excision and bypass . hulin and morris ( 4 ) reported a case of left psoas abscess collection that was treated successfully by open surgical drainage , authors attempted first ct guided drainage and conservative treatment that failed , without graft explantation . conventional surgical wisdom dictates that any infected prosthetic graft should be excised in - total to eradicate infection ( 3 ) . similarly , laser et al ( 5 ) treated 9 cases of aei all by open surgical explantation with in hospital mortality of 2 cases . this approach often means difficult and extensive surgery in these often very sick patients with generally high morbidity and mortality . we elected to treat our patient with intravenous antibiotics and ct guided drainage because the abscess seemed fairly localised and there was little perigraft collection . in conclusion patients with psoas collections following evar can be successfully managed by conservative mean and prolonged antibiotics in selected cases .

aortic stent graft infection is a rare but serious complication associated with high mortality . this report emphasizes the need for continued awareness of potential graft - related septic complications in patients undergoing endovascular aortic repair ( evar ) . we report a case in which a post - evar patient became unwell about 30 days post operatively and was shown on ct scanning to have a psoas abscess . the abscess was managed with percutaneous drainage and antibiotics . the patient remains well with no evidence of psoas collection or perigraft infection one year on . we review the available literature and discuss the merits of different management strategies .

plaque rupture or endothelial erosion with subsequent occlusive thrombus formation is the primary cause of acute coronary syndrome ( acs)- . it has been generally accepted that plaque vulnerability is an underlying mechanism for this local phenomenon . however , plaque instability may reflect a pan - vascular process with the potential to destabilize the plaques in nonculprit areas . several studies have suggested that vulnerable plaques exist at nonculprit lesions , as well as in the culprit site in acs patients . moreover , acs patients who underwent percutaneous coronary intervention ( pci ) had a similar recurrent adverse cardiac event rate in culprit lesions and nonculprit lesions ( 12.9% versus 11.6% during a 3-year follow - up period ) . therefore , detection of these non - obstructive , vulnerable plaques may play an important role in the prevention of acute myocardial infarction ( ami ) and sudden cardiac death . a 49-year - old man was admitted with a 3-hour history of sudden onset of substernal chest pain . he had an irregular medical history of hypertension for 5 years and hypertriglyceridemia for 12 years , and had a long history of smoking and drinking . he had no history of spontaneous bleeding , diabetes mellitus , stroke , atrial fibrillation , or family history of coronary artery disease . on admission , his cardiac enzymes , including myoglobin , were normal . his initial electrocardiogram ( ecg ) showed st - segment elevation in the inferior ( ii , iii , and avf ) and posterior ( v7v9 ) leads ( fig . 1 ) , while there was st - segment depression in the anterior ( v1-v4 ) leads , which may indicate acute inferior and posterior myocardial infarction . the patient underwent primary angioplasty after receiving aspirin ( 300 mg ) and clopidogrel ( 300 mg ) . coronary angiography revealed that the left circumflex artery ( lcx ) was acutely and totally occluded at the mid - portion ( fig . 2a ) and the proximal and mid - portion of the right coronary artery ( rca ) had a 60% occlusion ( fig . after percutaneous transluminal coronary angioplasty ( ptca ) was carried out in the lcx , lesions of the lcx had a hazy filling defect , which suggested an acute thrombus , and thrombus aspiration was conducted . mmol / l , triglycerides ( tg ) 5.35 mmol / l , high density lipoprotein ( hdl ) 0.75 mmol / l , low - density lipoprotein cholesterol ( ldl ) 2.25 mmol / l , lipoprotein a ( lp(a ) ) 179 mg / l , uric acid ( ua ) 445 mol / l , and nt - probnp 759 ng / l . a 2d - echocardiogram was performed and showed left ventricular ejection fraction ( lvef ) of 67.8% , with no regional wall motion or valvular abnormalities . the patient was discharged home 12 days later on aspirin ( 100 mg qd ) , clopidogrel ( 75 mg qd ) , atorvastatin ( 20 mg qn ) , ezetimibe ( 10 mg qd ) , and trimetazidine ( 20 mg tid ) . a : the left circumflex artery was acutely and totally occluded at the mid - portion . b : the proximal and mid - portion of the right coronary artery had a 60% occlusion . c : the proximal and mid - portion of the right coronary artery had a 90% occlusion . three weeks post discharge , he recovered without any symptoms and the test results showed values of : tc 2.89 mmol / l , tg 3.31 mmol / l , hdl 0.82 mmol / l , ldl 1.76 mmol / l , lp(a ) 45 mg / l , and ua 460.3 mol / l . however , one week later , the patient had an eventful course with recurrence of chest pain . ecg showed that r waves of ii , iii , and avf leads were flat , and exhibited qs model of v7-v9 leads . 2d - echocardiography examination showed that left ventricular lateral wall motion had decreased and lvef was 57.1% . ect showed myocardial ischemia and regional wall motion abnormalities in the left ventricular lateral wall , as well as inferior wall . coronary angiography showed no significant stenosis in the previous lcx lesion , while the proximal and middle potion of the rca had a 90% occlusion ( fig . 2c ) . after the procedure , the patient had a stable course with no recurrence of chest pain . it is known that acs patients are at high risk for recurrent ischemic events caused by a lesion that is anatomically unrelated to the initial event . our case supports the concept that acs is a pan - vascular process with a higher prevalence of vulnerable plaques in nonculprit sites , leading to recurrent ischemic events in the future . most ( 83.3% ) of the plaque ruptures of nonculprit artery in a previous study were observed in st - elevation mi patients . reported plaque ruptures somewhere other than the culprit lesion in 79% of patients with acs . pci patients with nonculprit coronary lesions underwent additional clinically driven pci at rates of 7.7% at 1 year , 14% at 2 years , and 16% at 3 years because of the progression of preexisting nonculprit coronary lesions . because of the rarity of the condition , fractional flow reserve assessed by intracoronary pressure wire is useful in deciding whether to revascularize angiographically moderate nonculprit lesions in patients with acs- . previous studies have shown that inflammation plays a pivotal role in the development of atherosclerosis and inflammation factors such as c - reactive protein are involved in the progression of nonculprit lesions- . acs correlates with systemic markers of inflammation , so high recurrent events may be related to additional vulnerable lesions distant from the culprit lesion . these observations support the concept that plaque instability is not merely a local vascular accident but rather probably reflects more generalized pathophysiological processes with the potential to destabilize atherosclerotic plaques throughout the coronary tree . despite achieving very low levels of ldl - c , many patients continue to show disease progression . on - treatment tg < 150 mg / dl was independently associated with a lower risk of recurrent coronary heart disease ( chd ) events , lending support to the concept that achieving low tg may be an additional consideration beyond low ldl - c in patients after acs . hyperinsulinemia is associated with an increased lipid content and a greater plaque volume of nonculprit intermediate lesions in nondiabetic patients with acs , suggesting that plaque vulnerability is increased in this subgroup of patients . acs , multivessel diseases , hdl - c and smaller increases in hdl - c were associated with the progression of nonculprit coronary lesion , , . this finding highlights the need for intensive modification of global risk in patients with coronary artery disease . thrombus was identified more frequently in infarct - related arteries than non - infarct - related artery lesions in the previous study . these reports all primarily showed that lesion - specific morphologies determined plaque instability and patient symptoms . subclinical episodes of plaque disruption , local thrombin activation , and subsequent healing with incorporation of thrombus into the vessel wall may represent one pathway for episodic progression superimposed on the slower systemic process . this concept is supported by previous angiographic studies showing rapid progression of stenosis with complex angiographic features . after successful pci of all angiographically significant lesions , overall untreated atherosclerotic burden remains high , and plaque burden lesions are frequently present in the proximal and mid - coronary tree . patients with plaque burden lesions have greater atherosclerosis throughout the coronary tree , have more thin - cap fibroatheromas , and are at increased risk for future cardiovascular events . to sum up , plaque disruption and healing occur not only at the culprit lesion but may be a pan - coronary process in patients with ami . three such devices have emerged and received the usa food and drug administration approval with claims that are theoretically capable of identifying certain characteristics of a thin cap fibroatheroma : radiofrequency intravascular ultra - sound ( rf - ivus ) , optical coherence tomography ( oct ) , and near - infrared spectroscopy ( nirs ) . so , how should these imaging tools be validated as potential detectors of vulnerable plaque ? secondly , most patients with coronary atherosclerosis are already prescribed high - dose statins . despite attainment of an ldl - c level of less than 1.8 mmol / l , nonculprit coronary lesions had still progressed , mainly in preexisting nonculprit artery lesions rather than de novo nonculprit artery lesions . one previous study demonstrated that early aggressive lipid - lowering therapy , via atorvastatin for 6 months , significantly reduced the plaque volume in patients with acs . we recommend intensive treatment for the culprit lesion and other severe lesions after careful consideration , in a staged fashion if necessary . one meta - analysis supports current guidelines discouraging performance of multivessel primary pci for stemi . when significant nonculprit vessel lesions are suitable for pci , they should only be treated during staged procedures . one study suggests that multivessel pci is effective and safe for chinese patients with st - segment elevation ami and simple lesions in nonculprit arteries . however , other research showed that initial multivessel pci was associated with significantly increased risk of in - hospital death , all - cause death , and macce . in conclusion , randomized trials must ultimately be undertaken in patients with high - risk plaques to evaluate the use of either new more potent systemic therapies or focal / regional interventional therapies to demonstrate that treating vulnerable plaques before rupture is effective in preempting future acs . here , we describe the clinical presentation and interesting angiographic findings in a case of rapid progression of rca lesions six weeks after successful primary pci in the totally occlusion of the mid - portion of the lcx with a brief discussion of a possible mechanism in the context of current management options . this case report demonstrates the systemic nature of acute coronary syndromes , highlights the inherent instability of coronary artery disease , and supports the notion of aggressive secondary prevention in these patients .

abstractwe report a case of a 49-year - old man who was admitted with a 3-hour history of sudden onset of substernal chest pain . coronary angiography revealed that the left circumflex artery ( lcx ) was acutely and totally occluded at the mid - portion . in addition , the proximal and mid - portion of the right coronary artery ( rca ) had a 60% occlusion . we inferred that the lcx was the culprit artery and primary pci was successfully performed . six weeks later , the patient had an eventful course with recurrence of chest pain . coronary angiography showed no significant stenosis in the previous lcx lesion , while the proximal and middle potion of the rca had a 90% occlusion . our case demonstrates the systemic nature of acute coronary syndromes and highlights the inherent instability of coronary artery disease .

inverted papilloma is a benign epithelial growth extending into the underlying stroma of the nasal cavity and paranasal sinus . the tumor is well known for its invasiveness , tendency to recur and association with malignancy . in 1854 , ward first documented the occurrence of inverted papilloma in the sinonasal cavity . however , in 1935 , reingertz histologically described the nature of the tumor and noted its classic inverted nature in underlying connective tissue stroma . in 1971 , hymans reviewed several cases of this tumor and subdivided sinonasal papilloma into inverted , fungiform and cylindrical cell types . it is a rare benign tumor with incidence rate of 0.6 cases/100,000 people / year . it usually arises from the lateral nasal wall , in the middle meatus , often extending to the ethmoid and maxillary sinuses . in advance cases , extension into all of the ipsilateral peripheral nervous system may occur whereas intracranial growth and dural penetration are rare . the pathogenesis of this lesion remains unclear although allergy , chronic sinusitis and viral infections have been suggested as possible causes . a 26-year - old male patient resident of nagpur reported at a private e.n.t clinic with a chief complaint of a mass in the right nasal cavity since 3 years . the patient also gave history of right nasal blockage and nasal discharge since 3 years . the patient gave similar history of right sided nasal mass 5 years back , for which he was operated upon in a private clinic and the mass was removed . after few months , patient started experiencing intermittent nasal obstruction and nasal discharge in the absence of upper respiratory tract infection . however , as the time passed by these symptoms aggravated and he started experiencing some nasal mass inside right nasal cavity . on anterior rhinoscopy , a solitary , pinkish , pedunculated , irregular , firm mass was located in right nasal cavity . on probing , mass was attached to lateral wall of right nasal cavity and mass did not bleed on touch . computed tomography ( ct ) scan was advised and it revealed that the tumor was arising from middle meatus of right nasal cavity and there was widening of osteomeatal complex of right side . based on the clinical features and radiographic findings , a provisional diagnosis of papilloma was given . the mass was surgically excised by lateral rhinotomy with medial maxillectomy [ figure 1 ] and the excised tissue was sent to the department of oral pathology and microbiology for histopathological examination . gross examination revealed a single bit of soft tissue specimen of size approximately 3 cm 2 cm , pinkish - white in color , irregular in shape , firm in consistency with rough surface texture . on histological examination , the hematoxylin and eosin stained section showed polypoid tissue covered with pseudostratified columnar ciliated epithelium with admixed mucocytes ( goblet cells ) and intraepithelial mucous cysts at places , which showed inversion into the underlying connective tissue stroma to form large clefts , ribbon and islands . photograph showing lateral rhinotomy incision scanner view of the section shows an endophytic or inverted growth pattern consisting of markedly thickened squamous epithelial proliferation growing downward into the underlying connective tissue stroma to form large clefts , ribbons and islands ( h&e stain , x40 ) low power view shows the inverted papillomas with an endophytic or inverted growth pattern consisting of markedly thickened pseudostratified ciliated columnar epithelium growing downward into the underlying stroma ( h&e stain , x100 ) high power shows the epithelium to be composed of pseudostratified columnar cells admixed with mucocytes ( goblet cells ) and intraepithelial mucin microcysts ( h&e stain , x400 ) inverted papilloma ( synonym : ringertz tumor , trasitional cell papilloma , fungiform papilloma , cylindrical cell papilloma , schneiderian cell papilloma , epithelial papilloma , papillary sinusitis , soft papilloma and sinonasal - type papillomas ) can be defined as a group of benign neoplasm arising from the sinonasal ( schneiderian ) mucosa and is composed of squamous or columnar epithelial proliferation with associated mucous cells . the ectodermally derived lining of the sinonasal tract , termed as the schneiderian membrane , may give rise to three morphologically distinct benign papillomas ( schneiderian papillomas ) . the literature indicates that among sinonasal - type papillomas , the septal papilloma is the most common ; however , practical experience indicates that the inverted type is the most common subtype and the oncocytic type is the least common . in general , sinonasal - type papillomas occur over a wide age range but are rare in children ; however , septal papillomas tend to occur in a younger age group . inverted papillomas occur along the lateral nasal wall ( middle turbinate or ethmoid recesses ) , with secondary extension into the paranasal sinuses typically , the schneiderian papillomas are unilateral ; bilateral papillomas may also occur . in the presence of bilaterality , clinical evaluation to exclude the possibility of extension from unilateral disease should be undertaken . symptoms vary according to the site of occurrence and include airway obstruction , epistaxis and a symptomatic mass or pain . the viral etiology has been suggested in few studies and inverted papillomas are reported to be positive for human papillomavirus ( hpv ) on in situ hybridization and/or polymerase chain reaction . the hpv 6 , hpv 11 , hpv 16 , hpv 18 and epstein-barr virus have been isolated . whether there is a cause and effect between the presence of hpv and the development of inverted papillomas remains to be determined . radiological studies are commonly used to evaluate inverted papilloma with ct scan and magnetic resonance imaging ( mri ) scan being the most common . bony changes including bowing of the bones located near the mass are common ct findings . tumors involving the maxillary sinus may lead to widening of infundibulum on ct scan , making the uncinate process difficult to discern . bone - remodeling may be a better term to describe the changes that occur secondary to the constant pressure and mass effect on surrounding bony structures from inverted papilloma , commonly seen at the medial wall of the maxillary sinus and lamina papyracea . it is postulated that the bony skull base may have limited response to pressure caused by inverted papilloma , leading to more erosive changes rather than remodeling . mri scan with t1-weighted images with contrast and t2-weighted images can be used to differentiate between tumor mass and postoperative secretions . sometimes , in cases without bony destruction , neither ct nor mri is helpful in the qualitative diagnosis , but they at least provide the suspicion of a neoplasm . mri is the first imaging modality to perform in the follow - up after removal of inverted papilloma . however , in this case , mri was not performed since patient was poor . on gross appearance it is pink to gray in color , with frond - like projections extending from the bulk of the lesion , vary from firm to friable in consistency . histologically , inverted papillomas have an endophytic or inverted growth pattern consisting of markedly thickened squamous epithelial proliferation growing downward into the underlying connective tissue stroma to form large clefts , ribbons and islands . the epithelium varies in cellularity and is composed of squamous , transitional and columnar cells ( all 3 may be present in a given lesion ) with admixed mucocytes ( goblet cells ) and intraepithelial mucin microcysts . a mixed chronic inflammatory cell infiltrate is characteristically seen within all layers of the surface epithelium . the cells are generally bland in appearance with uniform nuclei and no piling up ; however , pleomorphism and cytoplasmic atypia may be present . the epithelial component may demonstrate extensive clear cell features indicative of abundant glycogen content . mitotic figures may be seen in the basal and parabasal layers , but atypical mitotic figures are not seen . the stromal components vary from myxoid to fibrous , with admixed chronic inflammatory cells and variable vascularity . intraepithelial mucocytes show intra cytoplasmic mucin positive material , which is mucicarmine positive and diastase resistant , pas positive . sinonasal inflammatory polyps are clinically similar but histopathologically epithelial alterations are seen in inverted papillomas and not in the inflammatory polyps . sometimes nonkeratinizing respiratory carcinoma mimics inverted papillomas and then they can be differentiated by the presence of dysplastic features in carcinoma . in verrucous carcinoma , characteristically , cleft - like spaces lined by a thick layer of parakeratin extending from the surface deeply into the lesion which is the hallmark of verrucous carcinoma , is seen and is absent in inverted papilloma . squamous cell carcinoma may present in the setting of inverted papilloma in three different circumstances . first , patients may present with small foci of squamous cell carcinoma within inverted papilloma . the patient may also present with malignancy as a separate synchronous lesion and not within inverted papilloma and finally , the patient may present with metachronous carcinoma in areas of prior resection of benign inverted papilloma . this association with malignancy , along with a propensity for invasion and recurrence , drives the treatment paradigm for inverted papilloma . treatment includes complete surgical excision , including the adjacent uninvolved mucosa , as the later is necessary as growth and extension along the mucosa results from the induction of squamous metaplasia in the adjacent sinonasal mucosa . initially , in 18 century , inverted papillomas were excised via a transnasal closed approach with head light illumination . in fact , these early procedures mimicked polypectomies . although the intent of these procedures were curative , recurrence rates of 4080% were unacceptably high . recurrence actually represents residual disease in most cases , so that basic problem facing the clinician is to determine adequate treatment . open approaches such as the lateral rhinotomy and midfacial degloving procedures allow increased tumor visualization and more complete resection including maxillectomy , which minimizes the recurrence rates . it is mandatory to resect not only the tumor but also to remove the mucoperiosteum in areas from which the tumor originates using the drill . intraoperatively histologic control by frozen section is strongly recommended but , unfortunately , it is not performed due to lack of knowledge or negligence on the part of surgeons . though the inverted papilloma comprises only 0.54% of all primary nasal tumor , one can suspect inverted papilloma if mass in nasal cavity seems to be arising from lateral nasal wall , with involvement of at least 1 paranasal sinus , presenting in male patient of the fifth and sixth decade of life . common symptoms include unilateral nasal obstruction , epistaxis and sinusitis with nasal discharge . although the intent of surgical procedures were curative , recurrence rates of 4080% were unacceptably high . recurrence actually represents residual disease in most cases , so that basic problem facing the clinician is to determine adequate treatment . open approaches such as the lateral rhinotomy and midfacial degloving procedures allowed for increased tumor visualization and more complete resection including maxillectomy , which minimizes the recurrence rates .

inverted papilloma is a benign epithelial growth in the underlying stroma of the nasal cavity and paranasal sinuses . the pathogenesis of this lesion remains unclear although allergy , chronic sinusitis and viral infections have been suggested as possible causes . the tumor is well known for its invasiveness , tendency to recur and association with malignancy . recurrence rates of inverted papilloma are unacceptably high , which actually represents residual disease in most cases . in this study , we have presented a case report and reviewed the histological features of sinonasal inverted papilloma .

cavernous hemangiomas ( chs ) are defined as benign vascular structures inserted within the neural tissue , occurring in the central nervous system , and consisting of a dilated vascular bed5 ) . existence in the epidural space without bone involvement is rare1,10 ) , and only 4% of all chs ( 0.22/1.000.000 ) are purely epidural1,10 ) . clinical symptoms are usually seen as slowly progressive paraparesis , myelopathy and localized pain1,5 ) . although magnetic resonance imaging ( mri ) is the best diagnostic method for this lesion , it is not a definitive one8 ) . we felt it appropriate to present this case because chs in the epidural space have rarely been encountered . a 55-year - old male patient was admitted to our clinic with complaints of back pain beginning two years previously . additionally , he had progressive spastic paraparesis in both lower extremities , and an inability to stand without support for the previous 3 months . upon neurological examination , the motor power in both lower extremities was ii - iii / v , deep tendon reflexes were hyperactive , and hypesthesia was present under the t10 - 11 level . the patient had no history ofurinary or fecal incontinence , and the laboratory tests were within normal limits . however , inthe thoracic , lumbar , and cervical mris performed for further investigation , a mass lesion was seen along the t7 - 8 vertebral body levels . 1a ) , with a slightly lower signal than the cerebrospinal fluid ( csf ) on the t2-weighted images ( fig . 1b ) , and slight heterogeneous staining on the gadolinium - enhanced t1-weighted images ( fig . additionally , it was observed that the spinal cord was displaced to the right side due to the mass ( fig . a t8 - 9 total laminectomy was performed and an approximately 31.5 cm sized ( fig . 3a ) dark - colored vascular mass with soft consistency was found in the epidural space without invasion of the dura ( fig . 3b ) , which was completely excised microsurgically . the histopathological examination revealed a cavernous hemangioma , composed of large dilated blood - filled vessels lined with flattened endothelium ( fig . ten days postoperatively , the patient could walk independently and reported reduction in the localized back pain . chs are collections of small capillaries covered with a single layer of endothelium , characterized by lobules , separated by fibrous connective tissue septa , and composed of irregular and dilated vascular channels6 ) . however , they create clinical signs with mass effects , fluid movement within vascular structure , hemorrhages , thromboses , and the formation of cysts or caverns6 ) . these lesions can occur in every region of the body ; however , the most common area of occurrence in the cranial region of the central nervous system is the supratentorial area8 ) . chs have rarely been seen in the spinal canal1,6,10 ) , while only 4% of all cavernous hemangiomas ( 0.22/1.000.000 ) are purely epidural chs1,10 ) . spinal chs appear at an average age of 40 ( 30 - 60 ) and are more common in women ( 70% ) . according to frequency , the localization in the spinal vertebrae can be listed in order of occurrence as in the thoracic ( 54 - 60% ) , cervical ( 30% ) , and lumbar ( 10% ) vertebral regions1,7,9 ) ; they are seen most commonly in the posterior part of the spinal canal1,9 ) . there are two currently accepted hypotheses in the literature with regard to the frequent occurrence in the thoracic vertebrae ; the first is that the thoracic epidural space is wider3,6 ) , while the second is that the resistance in the posterior part of the thoracic spinal canal is lower3,6 ) . besides the sizes are very diverse3,6,7 ) the localization of the ch in our fifty - five - year - old male patient was consistent with the literature . although clinical symptoms may vary according to the localization , size and biological behavior , slow progressive paraparesis ( 71% ) and radiculopathy ( 19% ) are seen most commonly1,6,7,8,9,10 ) . acute presentation may occur due to either extradural hemorrhageor thrombotic occlusion within the cavernoma , by causing rapid increase in the bulk of the lesion6,8 ) . in our case , , the demarcated lobular lesion appears isointensein the t1-weighted images , hyperintense in the t2-weighted images , and intensely homogeneous with contrast enhancement in the contrast - enhanced t1-weighted images3,9 ) . in case of intramedullary chs , a hypointense ring due to peripheral hemosiderin deposition and heterogeneous intensity in the center although differential diagnosis is most commonly required with schwannoma in mris , it may be confused with other neurogenic tumors , metastasis , lymphoma , meningioma , multiple myeloma , extraosseous ewing 's sarcoma , disc fragments or epidural angiolipoma6,8 ) . in our case , the absence of a hemosiderin ring , as well as the displacement of the spinal cord , slightly lower signal than the csf signal in the t2-weighted images , and slightly heterogeneous significant contrast involvement suggested epidural hemangioma6 ) . aim of the surgery should be total removal at first operation6 ) ; however , intraoperative bleeding and intramedullary placement may impede the total removal . although hemorrhage is rare in intramedullary chs , massive bleeding may be seen in epidural chs1,2,6,8,10 ) . in cases of incomplete removal due to bleeding and its localization , adjuvant radiotherapy may be required6,8 ) . in our case , the bleeding in the perioperative period could be controlled surgically and adjuvant radiotheraphy was not needed . chs are non - neoplastic vascular malformations rarely seen in the spinal region , leading to a variety of clinical symptoms . in mris , it is very difficult to distinguish these from schwannomas . in this case with this kind of spinal epidural ch , despite wrong diagnosis is likely to occur , the author could perform complete reomval of this vascular malformation microsurgically .

cavernous hemangiomas were first reported in 1929 by globus and doshay , and are defined as benign vascular structures developed between the neural tissues occurring in the central nervous system , consisting of a dilated vascular bed . cavernous hemangiomas comprise nearly 5 - 12% of all spinal vascular malformations ; however , existence in the epidural space without bone involvement is rare . only 4% of all cavernous hemangiomas ( 0.22/1.000.000 ) are purely epidural cavernous hemangiomas . in this case report , we removed a hemorrhagic thoracic mass presenting with progressive neurological deficits in a 55-year - old male patient . we found this case to be appropriate for presentation due to the rare occurrence of this type of cavernous hemangioma .

most of the cases are asymptomatic with the exception of a few that may present with mild abdominal pain and nutritional deficiencies . intestinal obstruction is an acute presentation that has been observed in a number of cases where there is an increased worm burden that may partially or completely block the intestinal lumen.1,2 we present a case that proved difficult to diagnose as the child s symptoms of subacute intestinal obstruction did not pair up with the radiological results , forcing us to take unusual measures for diagnosis . a 3-year-4-month - old child presented to the emergency department with the complaints of greenish vomiting and abdominal pain for 3 days . his vomiting bouts were continuous with a frequency of five to ten episodes a day he had a history of mild constipation for 1 year , for which he was being managed with a high - fiber diet . on examination , though mildly tachycardic ( heart rate of 125 beats per minute ) , his respiratory rate , temperature , and blood pressure were within reference range . laboratory investigations showed an increased leukocyte count ( 14.510 cells / l ; neutrophils , 79.9% ; lymphocytes , 10.9% ; eosinophils , 2.2% ; basophils , 0.1% ) without any abnormalities in serum concentrations of electrolytes , amylase , and lipase . supine x - ray of the abdomen was performed suspecting intestinal obstruction , which showed no abnormalities ( figure 1 ) . computed tomography ( ct ) of the abdominal region was done to rule out any anatomical or positional abnormalities of the intestine , with suspicion of a partial obstruction in the small intestine . the child was withheld oral food and fluid ( nil per os ) , and nasogastric tube was kept on low volume suction . barium meal and follow through were hence scheduled , which revealed growth of intestinal worms in the upper intestine at various sections , which were found to be the cause of partial intestinal obstruction , as shown in figure 2 . the number of worms found was quite low , leading to the inability of reaching a definitive diagnosis earlier . upon resolution of the patients vomiting bouts and the development of healthy bowel sounds , he was initially started on a liquid diet and his diet was progressed further . follow - up after 6 days showed complete resolution of symptoms with confirmation that the worms had been passed during defecation . this study was conducted with the written informed consent of the patients guardian , and was approved by the ethical review board of the aga khan university hospital . intestinal nematode infection is one of the leading five causes of intestinal obstruction in a third of the world s population . ascaris lumbricoides ( al ) is the most common form of helminthic infection responsible for several medical problems , especially in the developing countries.2 though a vast majority of cases are asymptomatic , infected patients may present with a potentially severe variety of pulmonary and gastrointestinal disturbances.13 ascaris helminthic infection is predominantly found in areas of poor sanitation and is associated with malnutrition , anemia ( iron deficiency ) , and impairments of cognition and growth . al usually affects the pediatric age group patients residing in low socioeconomic areas with malnutrition and immune deficiencies . the worms reside near the ileocecal valve without causing serious symptoms , unless the environment becomes too hostile for their survival , which may result in their migration to a more tolerable region in the intestinal tract . al migration may cause serious complications such as pulmonary ascariasis , pancreatitis , liver abscesses , cholecystitis , volvuli , intussusception , and intestinal obstruction.14 diagnosis with clinical symptoms , hematological investigations , and biochemical profile is usually inconclusive . testing the stool for ova is one of the initial tests that are done which aid in establishing a diagnosis . abdominal x - rays , ultrasound , and ct scans may be used to rule out other differentials that might give a similar presentation and visualize the al itself.5 in the case of our patient , following an inconclusive abdominal x - ray and ct scan , barium studies were planned and a barium meal and follow through were scheduled . barium studies were performed due to the clinical presentation of the patient in which upper intestinal obstruction was more likely the cause of discomfort . an abdominal x - ray and whole abdomen ct were within reference range , indicating that the large intestine had no abnormalities that could lead to the green vomitus the patient had initially presented with . exactly 250 ml of contrast was given to the patient and a series of images were taken thereafter . the first picture taken was right after the patient had completely ingested the contrast , and the last image was taken 1 hour after its consumption . a low - count al infestation usually presents as a diagnostic dilemma , as reported by lakshmi et al6 as the small group of worms keep migrating to more favorable areas , or the worm burden is very low to begin with . low worm counts may mimic several diseases , confounding the original diagnosis , hence delaying the treatment to relieve acute intestinal obstruction . x - ray of the abdomen in intestinal obstruction may show several air fluid levels . mortality rate of intestinal obstruction of children under the age of 10 years is below 6% . partial obstruction of the intestines from al infestation usually resolves spontaneously with conservative treatment which includes bowel rest , intravenous fluids , and nasogastric decompression.7 if the mechanical obstruction persists , the worms act as a fixed point leading to intussusception or volvulus formation.1,8 al may excrete toxins , leading to small bowel spasticity and inflammation . volvulus , intussusception , or increasing pressure to the intestinal wall will inevitably cause intestinal necrosis . if intestinal necrosis occurs , resection and primary anastomosis are a mandatory step in the management of the disease . medical therapy consists of treatment with antihelminthic drugs , mainly albendazole and mebendazole.7 a single dosing is usually curative in 85% of the patients . multiple dosing can be administered taking into account the worm count , efficacy , and adverse effects of the drugs.9 al should be kept in mind in preschool children with symptoms of sudden acute intestinal obstruction . barium studies are effective , simple , and a cheap alternative to ct abdomen in the diagnosis of acute - onset intestinal obstruction secondary to al infestation , if other imaging studies turn out inconclusive . the patient should be managed medically if bowel necrosis has not yet occurred . moderate to severe al infestation causing partial to almost complete intestinal obstruction managed medically results in a lesser hospital stay and lower mortality rates , in comparison to surgical management . al infestation is easier to diagnose in cases of a heavy worm count causing intestinal obstruction . partial bowel obstruction may often present as a confounding mix of several diseases , none with a characteristic diagnostic marker to reach a definitive diagnosis .

ascariasis is a common infestation in developing countries where there is poor hygiene . a majority of the cases are asymptomatic , with a few cases presenting with mild abdominal pain and nutritional deficiencies in the long term . here we present a case of a young boy who presented as a diagnostic dilemma , with signs of acute intestinal obstruction without any supporting radiological evidence . a barium study revealed the presence of low - burden ascaris infestation that was managed medically .

advances in dna sequencing technology are paralleled by advances in network mapping technologies , although network mapping may be more complicated because the biochemical species ( proteins , metabolites , rna and small molecules ) are diverse compared with genome sequencing ( dna only ) . although knowledge of networks is far from complete , the numbers of unknown interactions are moving from ' unknown unknowns ' to ' known unknowns ' . protein - protein binding interactions are being systematically mapped using mass spectrometry of protein complex components ( anne - claude gavin , embl , heidelberg , germany ) , and they are continuing to reveal interactions not anticipated by any existing data . in an advance that could revolutionize the yeast two - hybrid system , next - generation sequencing is being incorporated as the back - end read - out ( pascal braun , dana farber cancer institute , harvard university , usa ) . steady advances over the past several years have developed the two - hybrid system to the point that the false - positive rate is very low , with precision of high - throughput screens roughly equivalent to careful , small - scale studies . the significance of the next - generation sequencing application is that the coverage or true - positive rate , which in previous work has been low , could conceivably be increased to approach moderate to near full coverage of interactions amenable to two - hybrid assays . enhanced yeast one - hybrid systems are also providing increased coverage of regulatory interactions between transcription factors and dna ( marian walhout , university of massachusetts medical school , usa ) . lipids and interactions between membrane - localized proteins have been difficult to study using traditional methods . new protein - lipid binding assays are becoming available for medium - scale applications ( gavin ) . cell signaling networks are being mapped using membrane two - hybrid technologies ( igor stagljar , university of toronto , canada ) . much like protein structure pipelines that have increasingly focused on discovering novel folds , protein - dna binding assays are being focused on the transcription factors that are most likely to have novel binding motifs that can not yet be predicted by homology ( timothy hughes , university of toronto , canada ) . microarrays of spotted proteins provide continuing opportunities for novel functional screens , such as mapping kinase - substrate interactions at the genome scale ( heng zhu , johns hopkins university , usa ) . a final theme of new technologies is a push to measuring interactions and activities in living systems . a recent single - cell mass cytometry technology allows simultaneous measurement of about 30 parameters about a cell , including surface and functional markers ( gary nolan , stanford university , usa ) . the resulting data provide a dynamic view of cell development and an indication of drug activity . a growing number of statistical methods use network data to link a biological input to an output ( phenotype ) . in linear systems , given two out of three of input , system ( transfer function ) and output , we can reproduce what is missing . being able to do the same for biological systems would have great utility in predicting disease risk , developing new therapeutics , and so on . biology is more complicated because inputs and outputs are ill - specified , and knowledge of the system ( network ) is poor . nevertheless , network data are sufficiently complete that they are proving useful in linking biological inputs and outputs . an important new direction in algorithmic development is the integration of multiple data sources to provide a fuller picture of cellular activity . this is especially important in studying multiscale processes , such as animal development , in which protein - level interactions translate to patterns visible by eye . imaging data are now being harnessed to improve the inference of developmental regulatory pathways , with predictions validated by mutant studies ( nicholas luscombe , embl european bioinformatics institute , uk ) . even single - cell dynamic processes have been difficult to study because technologies that measure networks typically provide a static picture , requiring additional dynamic measurements to understand how network components change and networks reorganize over time . i described new methods for coupling interaction networks with transcription time series to provide a moving picture of network activity . data integration methods provide improved ability to predict disease outcomes ( kelvin zhang , university of california , los angeles , usa , and ontario institute for cancer research , canada ) , predict gene function ( quaid morris , university of toronto , canada ) , and map regulatory networks ( sushmita roy , broad institute , usa ) . combining data from genetic interactions , physical interactions and protein sequence provides a more accurate picture of how networks have evolved ( amy keating , massachusetts institute of technology , usa , and chad myers , university of minnesota , usa ) . network - based algorithms can assist in generating hypotheses about how a gene mutation leads to disease ( theresa przytycka , national institutes of health , bethesda , usa , and patrick aloy , institute for research in biomedicine , spain ) . metabolic models have been developed that can link biochemical measurements , such as metabolite uptake , to growth rate ( zoltan oltvai , university of pittsburgh , usa ) . these different contexts imply the existence of different network components ( proteins in signal transduction or gene regulation , micrornas , metabolites , lipids and small molecules ) and different network states . networks are usually not measured for a specific context , however , but rather through biochemical assays ( protein - binding microarrays , and yeast one - hybrid and two - hybrid systems ) or by superimposing data from many distinct conditions ( chromatin immunoprecipitation with microarrays ( chip - chip ) and with sequencing ( chip - seq ) , epistatic interactions , condition - specific pull - downs , or time series ) . several groups presented work showing how network state can be inferred by integrating heterogeneous datasets and how differences in network state correspond to differences in phenotype . recent work has demonstrated that network contrasts , defined as differences in interaction patterns measured in different conditions , can be more informative of biological processes than interactions measured in individual states . yeast genetic interaction screens have used small - molecule treatments to generate contrasts ( trey ideker , university of california , san diego , usa ) . contrastive analysis in cell signaling using a combination of genetics and small molecules provides insight into pathways relevant to leukemia ( thomas graeber , university of california , los angeles , usa ) . host - pathogen networks can be probed as a function of the pathogen genotype ; studies of human papilloma virus showed that high - risk and low - risk strains had interactions with different subsets of human host proteins ( david hill , dana - farber cancer institute , harvard university , usa ) . these observations may be valuable in human health , for example by identifying patient - specific differences in network state ( anna goldenberg , university of toronto , canada ) . an intriguing possibility is that some of the heterogeneity in network state may not be genetic but rather purely stochastic ( suzanne gaudet , dana - farber cancer institute , harvard university , usa ) . beyond observing network activity is the challenge of shaping network state . future drug treatments may involve perturbing a network to control the response to drug treatment ( michael yaffe , massachusetts institute of technology , usa ) , or using computational techniques to identify key components of disease pathways ( andrea califano , columbia university , usa ) . finally , new synthetic biology technologies are providing an entirely new capability to rebuild biological systems from the dna up , with exciting applications to human health and bioenergy ( james collins , wyss institute , boston university , usa ) . individual datasets , focused on distinct types of interactions , are sufficiently complete to provide a coherent , though not yet seamless , framework of cellular behavior , from ligand - receptor interactions to cell signaling to transcriptional response . although these networks are often described as ' wiring diagrams ' , in reality the ability to predict the behavior of a biological system or to design a new system remains at the cusp of systems biology research .

a report of the systems biology : networks meeting , cold spring harbor , usa , 22 - 26 march 2011.the success of the human genome project has provided a model for an analogous interactome project to map how proteins , genes , metabolites and other regulatory components interact to transform a biochemical soup into a living system . these maps promise to serve as a framework for models that predict how a biological system responds to a perturbation or an input , which is relevant to gene mutations and therapeutic treatment in human disease , and as a framework for designing new systems in synthetic biology.three major themes arose during the 2011 meeting : technological drivers and data generation , algorithmic advances , and convergence on biological applications with context - sensitive networks .

miliary brain metastases , is an extremely rare form of brain metastasis and only 5% of all metastatic brain tumors consist of five or more lesions . clinical findings are very similar to metabolic / toxic or infectious encephalopathy on initial neurologic examination of the patients with miliary brain metastases . therefore , the physicians usually pursue other more frequent diseases that could explain clinical manifestations of these patients . in addition to a metastatic brain tumor , radiological differential diagnosis of these lesions includes miliary brain tuberculosis , neurocysticercosis or toxoplasmosis . nevertheless , because of similarity in appearances on different conventional magnetic imaging ( mri ) sequences , ( mri ) can not always provide enough information for differentiation of these lesions . although due to the different metabolic features of neoplastic and non - neoplastic lesions , the exact diagnosis can only be made by cerebral biopsy or by proton magnetic resonance spectroscopy ( mrs ) methods to enable differentiation between these lesions . the elevated choline ( cho ) levels along with spectrophotometric data analyses of other cerebral metabolite concentrations ( cho / cr and naa / cr ratios ) are the main markers for differentiation between neoplastic and non - neoplastic lesions by proton mrs . even if proton mrs does not change the leading diagnosis , it may rule out differential diagnosis and thereby it may reduce the diagnosing interval in patients with contrast enhanced miliary brain lesions on conventional mri . thus , early diagnosis and treatment can prevent morbidity , and can reduce the mortality rates in such patients . a 52-year - old previously healthy male patient was admitted to our emergency department with complaint of seizure and loss of consciousness after a minor head trauma . on admission , laboratory investigations including blood biochemistry , whole blood count , erythrocyte sedimentation rate , thyroid functions , and urinalysis results were all within normal limits . brain computed tomography ( ct ) revealed edematous regions at the inferior sections of both parietal lobes [ figure 1 ] . afterwards , contrast - enhanced mri revealed innumerable multi - dimensional lesions on both supra- and infratentorial areas . majority of these lesions were oval in appearance , with iso- to low - intensity signals on t1- and high - intensity signals on t2-weighted images associated with surrounding edema . most of them had homogenous and others had ring - like enhancement of contrast medium . in the same session mrs was performed ; because of an increase in the cho level ( 1.6966 ) with elevated cho / n - acetylaspartate ( naa ) ( 1.6966/1.4029=1.2093 ) and lowered naa / creatine ( cr ) ( 1.4029/1.0950=1.2811 ) ratios on proton mrs , these miliary lesions were thought to be consistent with metastasis . presence of moderate lipid peaks was thought to be related to tissue necrosis as seen in high grade malignancy [ figures 2a d ] . although , in addition to metastatic brain tumor , infectious pathologies such as miliary brain tuberculosis , neurocysticercosis and toxoplasmosis were also included in differential diagnosis because of the similar radiological appearances . interestingly , whole - body pet ct revealed no primary tumoral focus , and tumor markers including nse , cea , ca 19 - 9 and serum s100 protein were within the normal range . lumbar puncture revealed normal opening pressure , and csf analysis showed only 1 cell/l with normal protein ( 0.32 g / l ) , lactate ( 1.8 mmol / l ) and glucose ( 0.72 multiple csf cultures were also negative . additionally , serological and immunological examinations of the blood and csf revealed no evidence of parasitic disease . all other analyses , including hiv serology , anti - hu 1 antibody and tuberculin skin test were negative . in order to reveal the nature of brain lesions , a cerebral biopsy was performed with stereotactic guidance and the following pathologic examination revealed malignant epithelial tumor infiltration characterized by solid nests of atypical cells having pleomorphic nuclei and eosinophilic cytoplasm [ figures 3a and b ] . the antibodies used included : cytokeratin 7 ( ov - tl12/30 , 1:150 , neomarkers ) , cytokeratin 20 ( ks20.8 , 1:100 , neomarkers ) , ttf-1 ( 8g7g3/1 , 1:50 , neomarkers ) , and surfactant ( 32e12 , 1:400 , novocastra ) . immunohistochemically , neoplastic cells were positive for cytokeratin 7 and ttf-1 whereas cytokeratin 20 and surfactant were negative [ figures 3c and d ] . in the light of histopathological findings after the diagnosis , thorax ct and bronchoscopy were performed , but revealed no pathology . brain ct revealed the edematous regions at the inferior section of both parietal lobes gadolinium - enhanced axial , and coronal t1-weighted mri section revealed multiple millimetric nodular lesions with homogenous enhancement in both cerebral hemispheres and the brainstem ( a , b ) , axial t2-weighted mri of the brain revealed multiple nodular lesions associated with surrounding edema ( c ) , proton mrs showed an increase in choline peak ( d ) pathologic specimen of cerebral biopsy . microscopic examination with h and e staining revealed infiltrating glial tissue by neoplastic cells ( original magnification 4 ) ( a ) , microscopic examination with h and e staining revealed solid nests of atypical cells having pleomorphic nuclei and eosinophilic cytoplasm ( original magnification 40 ) ( b ) , immunohistochemical examination of tissue sections showed neoplastic cells cytoplasms staining positively for cytokeratin 7 , and nuclear ttf-1 expression of neoplastic cells ( c , d ) the patient 's general medical condition was rapidly deteriorated under medical treatment and he died within a one month following whole brain irradiation ( 2000 cgy/5 fractions/1 week ) . miliary form of tumor metastasis throughout the brain has been firstly described by madow and alpers in 1951 with the term of carcinomatous encephalitis based on the clinical and histopathological findings . this condition is usually seen as an advanced stage of the primary disease , and the survival time of the patients with miliary brain metastases are fairly limited . investigations regarding the primary focus of miliary brain metastases have revealed that the majority of cases originated from a lung carcinoma because of easy accessibility of the systemic arterial circulation by tumor cells in the lung . in the treatment of such lesions , whole - brain radiotherapy ( wbrt ) although , gefitinib has been reported to be a useful additive drug for resolution of the multiple metastatic lesions ; even though further researches are still necessary.[68 ] clinical manifestations of patients with miliary brain metastases are usually silent and differ from patient to patient . a variety of neurological deficits ranging from short and long term memory defects to hemiparesis may be present . however , neurological findings can strangely be minimal in a majority of patients with multiple lesions , perhaps due to weak edematous effects of these masses . plain skull films and brain ct have limited diagnostic value as calcification is rarely seen in these tumors . they are seen as nodular millimetric lesions with perivascular spreading , showing iso- to low - intensity signals on t1- and high - intensity signals on t2-weighted sequences of mri , and present a nodular or peripheral ( ring - like ) contrast enhancement following gadolinium injection . however , a large number of infectious and non - infectious diseases such as miliary brain tuberculosis , neurocysticercosis or toxoplasmosis , can cause multiple enhancing lesions in the brain with the dominance of infective pathologies . recently discovered proton mrs imaging technique is a potent instrument to analyze and monitor tissue metabolism noninvasively . it reflects alterations of the intracellular metabolite concentrations , such as cho , cr , naa , lactate and lipids on pathologic tissue that differs from normal brain tissues . on proton mrs , non - neoplastic lesions such as cerebral infarctions and brain abscesses had noticeable decreases in cho , cr , and naa levels while tumors have generally elevated cho and decreased levels of cr and naa . mller - hartman et al , reported that intracranial metastatic lesions showed strongly elevated lipid levels on proton mrs , with statistically significant differences from all other intracranial mass lesions , except tuberculosis abscess origin , or in cases of toxoplasmosis . recognition and prompt diagnosis of other contrast enhanced miliary brain lesions are important because early treatment can prevent patient from worsening , and lead to clinical improvement . proton mrs may also serve as a diagnostic tool to differentiate miliary brain metastases arise from different unknown origins . thereby , it may reduce an extended search for diagnosing of a primary unknown neoplasm and number of diagnostic biopsies has been used for differential diagnosis . a histopathologic examination is important for diagnosis ; especially in patients with primary tumor focus can not be found with other studies . to our knowledge , only 17 patients with pathologically proven diagnosis of miliary brain metastases have been reported until now . the most common histological type was adenocarcinoma where , lung was the most common primary site of origin . thyroid transcription factor-1 ( ttf-1 ) is a tissue - specific transcription factor which is expressed by epithelial cells in the thyroid and the lung . ttf-1 is a very sensitive and specific marker to document the pulmonary origin of an adenocarcinoma . the combinations of ck7 positive / ck 20 negative immunophenotype along with ttf-1 immunoreactivity were highly specific for primary pulmonary adenocarcinoma . in our case , immunohistochemical examination showed that neoplastic cells were positive for cytokeratin 7 and ttf-1 whereas cytokeratin 20 and surfactant were negative . depending on the immunohistochemical findings , lung was considered to be a possible primary site of origin and moderately or poorly differentiated adenocarcinoma of the lung was considered as histological subtype . the clinical , radiological and pathological features of miliary metastatic tumors have not been clarified yet , and there are no definite data on the stages and spread phases of the lesions in the brain . despite the advances in technical equipment and medical knowledge the differential diagnosis of miliary metastatic brain tumors is difficult . distinguishing non - neoplastic lesions from neoplastic lesions are extremely important because a misdiagnosis can lead to unwarranted neurosurgery and exposure to toxic chemotherapy or potentially harmful brain irradiation . nowadays , the pathological examinations of the tissue samples are still the gold standard for the diagnosis of miliary brain metastasis .

miliary brain metastases , also termed as carcinomatous encephalitis , are an extremely rare form of cerebral metastasis . here in this article , we report a 52 year - old male patient with miliary brain metastases originating from occult lung adenocarcinoma . there were no significant findings on his initial physical and neurological examinations except limited cooperation . brain computed tomography revealed edematous regions at the inferior sections of both parietal lobes . then after , the contrast - enhanced magnetic resonance imaging revealed innumerable multi - dimensional lesions associated with surrounding edema on t2-weighted images . the proton magnetic resonance spectroscopy revealed increases in the choline and lipid peaks with decreased n - acetylaspartate in a similar manner with metastatic brain tumors . histopathological findings pointed out that malignant epithelial tumor metastasis were originating in primary lung adenocarcinoma . despite the advances in technical equipments and medical knowledge , miliary metastatic brain tumors are quite rare and the differential diagnosis is difficult . our aim in this article was to present this rare case in which the lung was thought to be the primary focus ; and outline the radiological characteristics . also , we believe that the findings presented by proton magnetic resonance spectroscopy may contribute to making a differential diagnosis .

systemic embolization occurs in 22 - 50% of patients of infective endocarditis ( ie ) . emboli often involve major arterial beds , including lungs , coronary arteries , spleen , bowel , and extremities . we report a case of embolic occlusion of arteriovenous fistula ( avf ) due to embolism from vegetations of . a 45-year - old male has been on regular follow - up for hypertension induced chronic renal failure for the last 10 years . he was also diagnosed with mitral regurgitation secondary to rheumatic heart disease . a right radio cephalic avf was secured about 3 years back when the serum creatinine was 4.5 mg / dl . he was initiated on maintenance hemodialysis 6 months ago through avf . during the 3 month of hemodialysis he also complained of headache , myalgia , night sweats , shortness of breath , and cough . cardiovascular system examination revealed absent first heart sound , a third heart sound and a holosystolic murmur of grade iii . there was no swelling , warmth or redness of avf or right upper limb on that day . the doppler of right upper limb revealed echogenic thrombus at proximal radial artery extending 2.8 cm from the bifurcation , and there was another thrombus at proximal ulnar artery . on color doppler , there was no blood flow at fistula . echocardiography revealed mitral regurgitation with jet area > 8 cm and vena contracta width > 7 mm , a large vegetation > 10 mm in diameter on posterior leaflet of mitral valve [ figure 1 ] , the leaflet was thickened and had restricted movement . aortic and tricuspid valves were normal , mild tricuspid regurgitation , and mild pulmonary arterial hypertension were recorded . he was treated with vancomycin ( 20 mg / kg after dialysis once in 3 days for 6 weeks ) and gentamicin ( loading dose : 1.5 mg / kg followed by 1 mg / kg / after every dialysis session for 2 weeks ) . on the day 2 of admission , avf was explored . la : left atrium , lv : left ventricle on exploration [ figure 2 ] , septic emboli were found lodged at the bifurcation of the brachial artery . the ulnar artery , having luminal continuity with the brachial artery at bifurcation , contained septic emboli . the walls of the distal brachial artery and proximal ulnar artery were glistening off white in color and firm in consistency . thrombectomy of the brachial artery proximal to the bifurcation was done through a transverse arteriotomy . a fogarty catheter was passed into the ulnar artery through the arteriotomy and the embolus removed . the rent at the origin of the radial artery were repaired and distal end ligated . intraoperative photograph showing brachial artery thrombectomy , necrosed origin of radial artery suture sealed with the distal end of radial artery ligated the fever subsided in 2 days . an echocardiogram after 4 weeks showed a reduction in the size of vegetation on the posterior mitral leaflet of mitral valve . the etiologies of vascular access thrombosis may be considered as those causing early ( 0 - 3 months ) or late ( > 3 months ) thrombosis . early thrombosis is most commonly due to a technical error such as a choice of poor vein or narrowing of the lumen of the artery or vein during anastomosis . thrombosis can also result from external compression for hemostasis , hypotension , dehydration , or early puncture of an immature vein . late thrombosis can be due to repeated trauma from needle punctures with subsequent fibrosis and narrowing , hypotension , dehydration , compression , or trauma . however , it is most commonly due to an acquired stenosis of the runoff vein , attributed to mechanical endothelial damage from the shearing effect of the high pressure or the pulsatile arterial blood flow in the venous system leading to venous intimal hyperplasia . this patient highlights that when there was a thrombosis of an avf with fever , ie should also be considered . the present patient had no other cause for sudden occlusion of avf as successful dialysis was done a day before , and there were no signs of inflammation then . thrombolytics are usually avoided in patients with septic embolization because of concerns about concurrent intracerebral mycotic aneurysms and the risk of hemorrhage .

a 45-year - old male on maintenance hemodialysis through right radio cephalic arteriovenous fistula ( avf ) also had mitral regurgitation . he presented with fever and chills of 2 days duration along with pain and swelling at median cubital fossa of right upper limb . local examination revealed warmth , redness , and tenderness at median cubital fossa . avf thrill was absent . echocardiography revealed vegetations on the mitral valve . an extensive search of literature did not reveal an instance of embolic occlusion of avf due to vegetations of infective endocarditis .

a new outbreak of die - offs among striped dolphins was detected in the gulf of valencia in early july 2007 . at the time of writing , unusual die - offs had also been recorded in dolphins from the southern coasts of the spanish mediterranean , balearic islands , catalonia , and the ligurian sea . between july and october 2007 , > 100 dolphins had been found stranded along the spanish mediterranean coast . some dolphins were stranded alive ; all had neurologic symptoms and died after being rescued . in the gulf of valencia , the number of stranded animals during july through august 2007 was similar to that recorded in 1990 during the same months ( figure 1 , panel a ) . stranding rate was also similar during each episode , with an initial low rate at the beginning of july , 2 weeks with no stranded dolphins reported , and then a sharp increase of stranding in mid - august ( figure 1 , panel b ) . the most apparent difference between each episode was the size of animals collected : the mean size sd of dolphins collected in 1990 and 2007 was 180.9 28.6 cm ( n = 34 ) and 159.9 40.9 cm ( n = 17 ) , respectively . this difference is statistically significant ( student t test , t = 2.14 , 49 df , p = 0.037 ) . stranding patterns of mediterranean striped dolphins , stenella coeruleoalba , in the gulf of valencia and adjacent waters ( valencian community ) ( 514 km of coastline ) . b ) cumulative percentages of dolphins found dead during july august , 1990 and 2007 epizootics . we examined 10 dolphins ( 5 adults and 5 juveniles ) immediately after their death and collected samples of brain , lung , spleen , liver , and lymph nodes for histologic and molecular studies . immunohistochemical examination for dmv antigen was performed . a monoclonal antibody to canine distemper virus ( moab cdv - np , vmrd , inc . , pullman , wa , usa ) , known to react with dmv , was used as primary antiserum at a dilution of 1:200 . the secondary antibody , a biotinylated goat anti - mouse immunoglobulin serum , was used at the same dilution . finally , the avidin - biotin peroxidase complex was incubated at a dilution of 1:100 . lesions comprised multifocal bronchiolo - interstitial pneumonia with syncytial cells and nuclear inclusions in the alveolar epithelium and syncytia , as well as lymphoid depletion of the cortical area of the lymph nodes . in 1 dolphin , diffuse pyogranulomatous pneumonia of probable bacterial origin , with disseminated foci to many organs ( e.g. , brain , heart , lymph nodes , spleen ) , was found concomitantly with dmv infection . for 5 dolphins , immunostaining was observed in epithelial cells and syncytia in the lungs ( figure 2 , panel a ) , lymphoid cells , neurons , and/or bile duct epithelium . the staining pattern was similar to that described for animals affected by the 1990 epizootic ( 8) . a ) immunohistologic staining of lung tissue with a moab anti cdv - np , counterstained with hematoxylin . the evolutionary distances were computed with the kimura 2-parameter method and are in the units of the number of base substitutions per site . the tree is drawn to scale , with branch lengths in the same units as those of the evolutionary distances used to infer the phylogenetic tree . details of each isolate used for this study and accession numbers for each of the sequences are as follows : dmv 2007 isolate ( eu124652 ) , pmv g12 isolate ( ay949833 ) , pprv nigeria/75/1 vaccine ( x74443 ) , pdv dk/88 strain ( x75717 ) , rpv rbok vaccine strain ( z30697 ) , dmv isolate ( aj608288 ) , cdv onderstepoort vaccine strain ( af305419 ) , and mv edmonston vaccine strain ( af266288 ) . dmv , dolphin morbillivirus ; pmv , porpoise morbillivirus ; pprv , peste des petits ruminants virus ; pdv , phocine distemper virus ; rpv rbok , rinderpest virus rbok strain ; cdv , canine distemper virus ; mv , measles virus . tissues from the 3 dolphins analyzed by immunohistochemistry were also examined for morbillivirus nucleic acid by reverse transcription pcr ( rt - pcr ) . we used nested sets of universal morbillivirus primers ( upn1 : 5-acaaaccnagrattgctgaaatgat-3 [ genome position 844869 ] ; upn2 : 5-ctgaayttgttctgaaytgagttct-3 [ position 10571081 ] ) based on the conserved n terminus of the morbillivirus n gene . tissue samples from 1 dolphin tested positive by n1/n2 , and the product was sequenced in its entirety . pcr with nested primers ( n1a : 5-actatyaarttyggnatngaacnatgt-3 [ position 906932 ] ; n2a : 5-ctgcactraayttgttytgrayngagt-3 [ position 10441071 ] confirmed the other samples as positive . the n1/n2 sequence ( european molecular biology laboratory accession no . eu124652 ) was aligned to the same region for each of the morbilliviruses with clustalw ( www.ebi.ac.uk/clustalw ) ( the primer sequences having been removed ) ; phylogenetic studies were performed with the mega ( version 4 ) package ( www.megasoftware.net ) . this alignment indicated that this strain was very closely related to the virus that caused the epizootic in 1990 ( figure 2 , panel b ) . overall , 7 of the 10 dolphins ( 4 of 5 adults ; 3 of 5 juveniles ) examined during this study were positive for dmv by immunohistochemistry or pcr . pcr products spanning other viral genes are currently being generated and sequenced to develop a more detailed phylogenetic analysis of the virus currently circulating . these results show that dmv is again circulating in the mediterranean population of striped dolphins . the new epizootic resembles the previous die - offs in 1990 : both epizootics began in approximately the same region and at the same time and , according to the stranding patterns ( figure 1 , panel b ) , have followed a similar course of infection . however , in the current epizootic , younger animals were apparently more severely affected by the disease . although these results are based on stranded dolphins and stranding rates do not necessarily correlate directly with death rates ( 9 ) , we are comparing data from the same area for the 2 epizootics . we are also aware that we used a surrogate of age ( i.e. , standard length ) for these comparisons . however , standard length correlates with sexual maturity ( 10 ) and has been repeatedly used as proxy for age ( 5 ) . finally , diseased dolphins are still being detected in late 2007 ; more juveniles than adults are affected . these observations further indicate that dmv did not persist as an enzootic infection in the mediterranean striped dolphins after the 19901992 epizootic , that adult dolphins that had survived the first epizootic still had some immunity against the virus , and that unpredictable epizootics may recur . the relatively high density of striped dolphins , their gregarious behavior , and the decreasing level of specific immunity will likely favor the propagation of the virus among the entire mediterranean population . for this reason , abnormally high die - offs might be expected in other areas of the mediterranean sea in the coming months , and measures should be taken to recover and analyze the carcasses . recurrent morbillivirus epizootics in marine mammals were described in harbor seals , phoca vitulina , from northern europe ( 1114 ) and bottlenose dolphins , tursiops truncatus , from the western atlantic and gulf of mexico ( 15 ) . two major questions need to be answered concerning these phenomena : 1 ) what was the source of infection or reinfection , and 2 ) did environmental stress ( e.g. , pollutants , adverse weather , fisheries ) precipitate the epizootics ( 9 ) ? in the case of the mediterranean striped dolphin , the answer to the first question is far from clear , but that both epizootics began in a region close to the gibraltar straits , where contacts with infected cetaceans of atlantic origin could have occurred , is perhaps not coincidental . with regard to the second question , striped dolphins killed by the disease in 1990 had particularly high polychlorinated biphenyls levels , and water temperatures were abnormally high during the winter before the epizootic ( 2 ) . the role of these environmental factors in the 2007 epizootic remains to be more fully investigated . recurrent epizootics with high die - offs among all age classes will probably have a negative affect on the population dynamics of mediterranean s. coeruleoalba .

in july 2007 , > 100 striped dolphins , stenella coeruleoalba , were found dead along the coast of the spanish mediterranean . of 10 dolphins tested , 7 were positive for a virus strain closely related to the dolphin morbillivirus that was isolated during a previous epizootic in 1990 .

with the introduction of the 7th edition of the tnm staging system , it was suggested that this system should be used not only for staging of non - small cell lung cancer ( nsclc ) but also for small cell lung cancer ( sclc ) and bronchopulmonary carcinoids . thus , it replaces the much simpler staging system previously used for sclc ( veteran administration staging system ) reflecting the advances in therapy and prognosis achieved recently ( table 1 ) . table 1tnm staging system 7th editionstageclassificationt1tumour <3 cmnew : t1a < 2 cmnew : t1b : 23 cmno infiltration of visceral pleura / main bronchusno atelectasist2tumour > 3 cmnew : t2a : < 5 cmnew : t2b : 57 cminfiltration of visceral pleurainfiltration of main bronchus 2 cm of carinapartial atelectasist3infiltration of parietal or mediastinal pleura , chest wall , pericardium , diaphragm infiltration of main bronchus < 2 cm of carinaatelectasis of complete lungnew : tumour > 7 cmnew : satellite nodule in the same lobe ( previously t4)t4infiltration of irresectable structures / organs ( mediastinum , heart , major vessels , trachea , recurrent laryngeal nerve , oesophagus , vertebral body , carina)new : satellite nodule in a different lobe of the ipsilateral lung ( previously m1)new : no longer malignant pleural / pericardial effusion ( now m1a)n1ipsilateral peribronchial , hilarn2ipsilateral mediastinal ( incl . subcarinal)n3contralateral hilar , mediastinalipsi-/contralateral , supraclavicular or scalene lymph nodes ( m1 : cervical or abdominal lymph nodes)m1new : m1a : malignant pleural / pericardial effusion ( previously t4)new : m1b ( previously m1):haematogenous distant metastases ( brain , liver , adrenal , bones , etc.)lymphatic distant metastases ( cervical , abdominal lymph nodes)satellite nodules in contralateral lung ( previously : in other lobes than the primary tumour ) tnm staging system 7th edition t staging describes the local extent of a tumour , i.e. infiltration of adjacent structures or organs that has an effect on resectability and prognosis . in the 6th edition tumour size was only used to differentiate between t1 ( 3 cm ) and t2 ( > 3 cm ) . this has been modified so that tumours > 7 cm are now classified as t3 independent of other features , and subclassifications have been introduced to describe tumours with a maximum diameter of up to 7 cm by their size more precisely : t1a ( 2 cm , t1b : > 23 cm , t2a : > 35 cm , t2b : > 57 cm ) . the other features describing infiltration of visceral or parietal pleura , mediastinum , chest wall or other organs have not been changed ( fig . this is classified as t1a in the 7th edition and was classified as t1 in the 6th edition of the tnm staging system . this is classified as t1a in the 7th edition and was classified as t1 in the 6th edition of the tnm staging system . n staging describes whether a lymph node metastasis is located within the visceral pleura , the ipsilateral or contralateral mediastinum , which affects therapy ( surgical resection , lymphadenectomy ) and prognosis . m staging describes the presence or absence of distant metastases . these usually represent systemic and irresectable disease and a very poor prognosis . with the 7th edition a differentiation was introduced between irresectable spread in the thorax , i.e. malignant pleural and pericardial effusion ( now m1a , formerly t4 ) and extrathoracic spread ( now m1b , formerly m1 ) ( fig . 2 ) . figure 2malignant pleural effusion and pleural tumour nodules of the left hemithorax . the changes in the t and in the m staging obviously affect tumour stages in individual cases .

abstractstaging systems aim to describe malignant tumours in a standardized fashion to assist in therapy planning and estimation of prognosis , allow comparison of different therapeutic strategies , facilitate communication between individuals and institutions , improve our knowledge of malignant disease and ultimately improve the outcome for patients . with the continuous increase in data and , ideally , our understanding of a disease and its potential therapy , every staging system requires continuous adjustment . the tnm staging system by the international union against cancer ( uicc ) is applied worldwide and revised regularly , with intervals aiming at a compromise between up - to - date information on the one hand and providing continuity by avoiding too short - lived revisions on the other hand . the 6th edition was published in 2002 and the 7th edition was published in 2009 . the 7th edition became current from january 2010 on .

patients with end - stage kidney disease undergoing chronic hemodialysis ( hd ) present higher mortality rates compared with the general population . once patients are on hd , the risk of cardiovascular death is approximately 30 times higher than that in the general population and remains 1020 times higher after stratification for age , gender , and the presence of diabetes . about half of the deaths of patients on dialysis are attributed to cardiovascular causes including coronary heart disease , cerebrovascular disease , peripheral vascular disease , and heart failure . end - stage renal disease ( esrd ) patients suffer from a state of chronic inflammation leading to cardiovascular complications , progressive malnutrition , and death [ 1 , 2 ] . inflammation is subclinical , and chronic disorders of the cytokine system or acute - phase proteins may be observed as the sole evidence of a proinflammatory disorder . according to this hypothesis traditional inflammatory biomarkers such as tumor necrosis factor - alfa ( tnf - alfa ) , c - reactive protein ( crp ) , and interleukin-6 ( il-6 ) have been shown to predict cardiovascular events in both symptomatic and asymptomatic individuals as well as those in the uremic population . low - grade chronic inflammation , as indicated by levels of high - sensitivity c - reactive protein ( hs - crp ) , prospectively defines the risk of atherosclerotic complications , adding to the prognostic information provided by traditional risk factors . provides convincing evidence that , in apparently healthy subjects , baseline serum levels of hs - crp are predictive of future myocardial infarction and ischemic stroke . subsequent meta - analysis of prospective population - based studies has compared patients in the lower tertile of hs - crp with those in the upper tertile [ 4 , 5 ] . with a good consistency between studies , a higher risk for major coronary events was observed for the upper tertile with the lowest tertile used as a reference . in general population most studies showed a dose - response relationship between the level of hs - crp and risk of incident coronary disease . recent papers also suggest association with incidence of sudden death [ 6 , 7 ] and peripheral arterial disease . through stratification or multivariable statistical adjustment , hs - crp retains an independent association with incident coronary events after adjusting for age , total cholesterol , hdl cholesterol , smoking , body mass index , diabetes , history of hypertension , exercise level , and family history of coronary disease [ 9 , 10 ] . in terms of prediction of recurrent cvd events and death , the strongest association with prognosis has been with hs - crp ; hs - crp consistently predicts new coronary events in patients with unstable angina and acute myocardial infarction [ 1120 ] . as elevated serum levels of hs - crp have been shown to be such a strong predictor of cardiovascular mortality in the general population , available data suggest that the association between inflammation and atherosclerosis is particularly strong in uremic patients [ 21 , 22 ] . reported that chronic inflammation enhances cardiovascular risk and mortality ; a few years later ikizler et al . in a prospective study assessed the importance of hs - crp values as independent determination of hospitalization in chronic hemodialysis ( hd ) patients recently , it has been shown that proinflammatory cytokines such as il-6 may exert a direct inflammatory effect on the heart and peripheral circulation . in a previous published paper , we investigated the joint predictive power of crp and il-6 , in order to ascertain what is the prognostic information that each index carries independently of the other . to this aim , il-6 and crp plasma levels were measured in a cohort of 218 esrd patients from different centres over a 4-year followup . this study showed that plasma il-6 rather than crp better predicts outcome in ersd patients . various possible explanations may underline the advantage of il-6 over crp as an outcome predictor . one possibility is that , being located upstream in the cascade of events which lead to the synthesis of many acute - phase reactants , il-6 is a better marker of the inflammatory burden affecting the development of cardiovascular disease . another possibility is that levels of il-6 vary less than those of crp , leading to a more accurate classification of patients at risk when one single sample is taken . finally , the toxic effects of il-6 on the heart and peripheral vasculature might be stronger than those of crp . first , it gives further support to the hypothesis about the role of inflammatory mediators in the genesis of cardiovascular disease in dialysis patients [ 2527 ] . secondly , it provides evidence suggesting the use of il-6 in addition to , or even in place of , crp for the identification of patients at risk . zhang et al . reported that there was no association between crp haplotypes and cardiovascular outcome in dialysis patients ; this study argues against crp as a cardiovascular risk factor . on the other hand , because variations within the il-6 gene were shown to affect the risk for cvd in a multiethnic dialysis cohort , this suggests that il-6 should be the target for interventional studies . according to these data , we suggest that all traditional risk factors for death should be measured accurately in uremic patients . clinical events should be identified prospectively , and , whenever possible , il-6 levels should be measured repeatedly during the course of followup . tnf - alfa , a proinflammatory cytokine ( 17 kda ) originally associated with killing of tumor cells , has a pivotal role in regulating both pro- and anti - inflammatory mediators . tnf - alfa has been regarded a master regulator of the cytokine cascade that provides a rapid form of host defense against infection but is fatal in excess . tnf - alfa is highly multifunctional with effects on lipid metabolism , coagulation , insulin resistance , and endothelial dysfunction . the major cellular origin of tnf - alfa , previously known as cachectin , is activated macrophages . it should be noted that , whereas il-6 is strongly associated with crp and other inflammatory biomarkers , the association between tnf - alfa and crp is rather weak . this suggests that circulating levels may be influenced by a number of different factors and that circulating tnf - alfa levels may not reflect biologic activity at the tissue levels . although available evidence suggests upregulated tnf - alfa system activity in esrd patients , data linking elevated circulating tnf - alfa levels to cvd and mortality have not been as clear as for il-6 . it is now generally accepted that cd40-cd40 ligand interaction is a main determinant of the proatherogenic phenotype . originally identified in b and t lymphocytes as being involved in t - cell - dependent b - cell activation and differentiation , the cd40-cd40 ligand system has been implicated in the pathophysiology of several chronic inflammatory diseases including risk factor - related vascular damage . cd40 , a 50 kda integral membrane protein of the tumor necrosis factor receptor family , and its cognate agonist cd40 ligand also known as cd154 , a transmembrane 39-kdalton protein structurally related to tumor necrosis factor - alpha , are coexpressed by several cells of the vasculature , including endothelial cells , smooth muscle cells , and macrophages . cd40 ligand also occurs in a soluble form ( scd40l ) that is considered to possess a full biological activity . increased scd40l levels have been described in obesity , hypercholesterolemia , diabetes [ 36 , 37 ] , and unstable angina . furthermore , it has been recently reported that circulating scd40l has a strong independent prognostic value among apparently healthy individuals and patients with acute coronary syndromes and represents an independent predictor of restenosis after percutaneous transluminal angioplasty . thus , the clinical association between soluble cd40l and cardiovascular events suggests that soluble cd40l function spans the time interval from early atherogenesis to late thrombotic complications . according to this , hocher et al . recently demonstrated during a follow - up period of 52 months that scd40l is an independent predictor of atherothrombotic events in patients on hd . more recently we expanded on this topic demonstrating that the prognostic value of scd40l is evident also in over 200 chronic hd patients from the riscavid population at 24-month followup ( riscavid , risk cardiovascular in dialysis is a prospective observational study performed on a large hd population in the northwestern region of tuscany , italy ) ( figure 1 ) . in this paper we were able to demonstrate that this prognostic value of scd40l is already evident at 24 months followup thus reinforcing the strong link between scd40l and clinical outcomes in patients in hd and suggesting a possible clinical use of this new promising biomarker to better define cardiovascular prognosis in these patients . the striking prognostic impact of scd40l on the clinical course in patients in hd raises questions about the origin of this biomarker . platelets represent the main source of circulating scd40l in patients with acute coronary syndrome and in hypercholesterolemia . accordingly , plasma levels of scd40l correlate closely with markers of platelet activation in these patient populations [ 35 , 38 ] . thus , increased circulating levels of scd40l might reflect an enhanced platelet activation in hd . according to this , it has been demonstrated that circulating activated platelets ( p - selectin / cd63-positive platelets ) are higher in hd patients than in controls and further increase during hd sessions . potential causes of such activation include possible stimulation of platelets by proinflammatory cytokines that have been reported to be increased in patients with end - stage renal disease . furthermore , the increased lipid peroxidation that has been found in patients with chronic renal failure might also participate in activating platelets . on the other hand , the lack of any correlation between circulating levels of scd40l and crp seems to exclude a role for this platelet - activating inflammatory biomarker in the enhanced scd40l signaling observed in our study population . pentraxin is a family of proteins considered to be markers of the acute - phase inflammation [ 48 , 49 ] ( figure 2 ) . currently , the pentraxin protein family is divided into two subfamilies based on size : the classical short pentraxin ( 25 kda ) and the long pentraxin ( 4050 kda ) . pentraxin 3 ( ptx3 ) is a long pentraxin that is highly expressed in the heart , whereas c - reactive protein ( crp ) is a short pentraxin and is produced from the liver . ptx-3 expression occurs in a variety of cell types , including endothelial cells , mononuclear phagocytes , dendritic cells , smooth muscle cells , fibroblasts , adipocytes , and epithelial cells in response to inflammatory cytokines and toll - like receptor engagement [ 5153 ] . in several recent studies [ 54 , 55 ] ptx3 appeared to be not only an early indicator of irreversible myocyte injury but also a prognostic marker in patients with acute myocardial infarction . reported the acute - phase protein ptx3 as a predictor of 3-month mortality after adjustment for major risk factors and other acute - phase prognostic markers . in a recently published paper of barbui , the role of ptx3 as a prognostic biomarker was shown by an increased serum ptx3 that was closely related to death due to mi , in - hospital or to 6 months , in acs patients , including stemi , nstemi , and uap groups . more recently , suliman et al . analyzed plasma ptx-3 concentrations in relation to comorbidities ( davies score ) , protein - energy wasting ( pew ) , and inflammation markers in 200 prevalent hd patients , aged 64 14 years , who had been on hd treatment for a median period of 36 months . survival ( 42 months ) was analyzed in relation to ptx-3 levels ( high ptx-3 tertile versus two lower tertiles ) . this study shows that high levels of ptx-3 were found in prevalent hd patients with cvd and pew ; furthermore , a powerful association of ptx-3 with comorbidities was founded . as ptx-3 predicts mortality independent of age and comorbidities in prevalent hd patients , further designed studies addressing the clinical implication and pathogenic mechanisms of this long pentraxin are warranted . although the successful introduction of dialysis in the 1960s has increased life expectancy in patients with esrd , the mortality rate is still unacceptably high , due primary to a process of inflammation - associated accelerated atherosclerosis . the accelerated atherosclerotic process of esrd may involve several interrelated processes , such as oxidative stress , endothelial dysfunction , vascular calcification , and inflammation . the explosion of new knowledge on the central role of a dysregulated cytokine and th system activity has opened new and exciting opportunities for nephrologists to manage and prevent cvd and wasting in this diseased patient group . the use of several traditional and new biomarkers of inflammatory and cardiovascular risk is of great utility in this high - risk population .

cardiovascular disease is the leading cause of death in the general population ; traditional risk factors seem inadequate to explain completely the remarkable prevalence of cardiovascular mortality and morbidity observed in the uremic population . a role for chronic inflammation has been well established in the development of atherosclerotic disease , and , on the basis of these observations , atherosclerosis might be considered an inflammatory disease . inflammation has been implicated in the etiology of coronary artery disease in the general population , and traditional inflammatory biomarkers such as c - reactive protein ( crp ) and interleukin-6 ( il-6 ) have been shown to predict cardiovascular events in both symptomatic and asymptomatic individuals as well as those in the uremic population . later on , new nontraditional markers were related to the risk of cardiovascular morbidity and mortality in general and in uremic population . as a consequence of the expanding research base and availability of assays , the number of inflammatory marker tests ordered by clinicians for cardiovascular disease ( cvd ) risk prediction has grown rapidly and several commercial assays have become available . so , up to now we can consider that several new nontraditional markers as cd40-cd40 ligand system and pentraxin-3 seem to be significant features of cardiovascular disease in general and in esrd population .

renal allograft transplantation has been successful in chronic kidney disease ( ckd ) stage v patients with sickle cell disease or trait , although incidence of complications has been higher than other causes of ckd-5d . we report a case of sickle cell trait who had developed acute patchy renal cortical necrosis ( rcn ) following renal transplantation . a 32-year - old woman with sickle cell trait diagnosed on electrophoresis with confirmed sickling phenomenon ( on sodium metabisulfite preparation ) presented in january 2003 with accelerated hypertension , neuroretinopathy , and ckd stage v. she was initiated on regular hemodialysis . her pretransplant journey of 1 year was complicated with recurrent pulmonary edema due to breakthrough accelerated hypertension , acute pancreatitis , and tubercular osteomyelitis . kidney biopsy could not be done to establish the cause of ckd as patient had bilateral small kidneys . the cause appeared to be unrelated to sickle cell trait because of absence of prior episodes of sickling crisis or hematuria and presence of malignant hypertension , all uncommon features in sickle cell trait . triple drug immunosuppression with cyclosporine ( 8 mg / kg ) , prednisolone ( 0.5 mg / kg ) , and azathioprine ( 2 mg / kg ) was used along with induction therapy with basiliximab ( 20 mg on day 1 and day 4 of renal transplant ) . there was brisk post - transplant diuresis ( 10.5 l on first day and 6.5 l on the second day ) and serum creatinine normalized by second day ( 1.1 mg / dl ) as expected in a live renal transplant . she was noted to have spontaneous closure of av fistula ( on day 1 ) with accelerated hypertension which was controlled with nifedipine , clonidine , and atenolol . on day 5 , there was a rise in serum creatinine to 2 mg / dl from a base line of 1 mg / dl , which increased rapidly to 3.8 mg / dl by day 7 . however , her urine output remained above 3 l /day and blood pressure was normal ( 140/80 mmhg ) on three drugs . investigations showed leukocytosis ( wbc count > 13500/cu.mm ) with near normal hematocrit ( pcv 36% ) and normal liver function tests ( total bilirubin , 1 mg / dl ; sgot , 26 u / ml ; sgpt , 32 u / l ; serum proteins , 6.2 gm / dl ; and albumin , 3.5 gm / dl ) . ultrasonogram of graft was normal and radionuclide study of graft showed mild reduction of perfusion with prolonged parenchymal transit . cyclosporine c2 level ( fluorescence polarization immunoassay ) on day 7 was 1932 g / l ( target , 1700 g / l ) . graft biopsy done on day 10 showed 15 glomeruli ( two viable ) with necrosed surrounding tubules , patchy inflammatory infiltrates , and no arteritis [ figure 1a and b ] . acute patchy cortical necrosis was diagnosed and possibility of renal graft rejection or thrombotic microangiopathy as possible alternative diagnosis excluded . the renal function showed an improving trend ( s. creatinine , 3 mg / dl ) . after 4 days , she developed severe pancytopenia ( wbc count , 1000/cu.mm ; platelet count , 30 000/cu.mm ; and hb , 7.5 gm / dl ) . mmf was discontinued and supportive therapy for anemia / leucopenia was given with granulocyte colony stimulating factor , antibiotics , and blood transfusion . later , sirolimus , mmf , and azathioprine were tried one after the other as second agent but were unsuccessful because of recurrence of leucopenia with each of them . hence , patient was continued only on high dose of prednisolone 40 mg / day till 6 weeks when her serum creatinine stabilized at 2.2 mg / dl . she was restarted on low - dose cyclosporine ( 2 mg / kg / day ) which was well tolerated , serum creatinine remaining stable . she was discharged from hospital after 7 weeks post - transplant on prednisolone 30 mg / day and cyclosporine 50 mg twice daily ( 2 mg / kg / day ) with serum creatinine 2.2 mg / dl and hb 9.9 gm / dl . at 72 months follow - up , she is doing well ( serum creatinine , 1.2 mg / dl ; hb , 11.5 gm / dl ; and leukocyte count , 10 200/cu.mm ) and is on low - dose immunosuppression ( prednisolone , 7.5 mg / day and cyclosporine , 1.5 mg / kg / day ) . ( a , b ) renal histology ( pas staining , 400 magnifications ) showing necrotic areas having ghost outlines of glomeruli and tubules with loss of cellular details renal manifestations of sickle cell disease are hematuria , renal infarction and papillary necrosis , diminished concentrating ability , renal tubular acidosis , abnormal proximal tubular function , acute renal failure , progressive renal failure with proteinuria ( sickle cell nephropathy and less commonly mpgn ) , and renal medullary carcinoma . relative low oxygen tension of renal arterial system and hypertonic acidic renal medulla combine to promote local red blood cell sequestration , leading to progressive renal ischemia / infarction and interstitial fibrosis . higher incidence of infection , disease recurrence , and sickling crisis due to improved hematocrit and blood viscosity have contributed to relatively poor long - term clinical outcome in these patients as compared with other etiologies of renal failure after renal transplantation . though 1 year patient and allograft survival rates are similar to that of other categories of renal transplantation , 3 year graft survival rate is reported to be significantly inferior . despite these reported adverse outcomes , long - term survival after renal transplant is still superior to hemodialysis ( median survival , 35 vs 24 months ) in patients of sickle cell disease . in contrast to sickle cell disease , patients of sickle cell trait have usually benign course with sickling crisis not noted except in extremes of metabolic derangement ( e.g. , severe acidosis ) . the possibility of alternative diagnosis of basic disease , specifically compound heterozygote of sickle cell disease ( hb sc and sickle cell - beta ( + ) thalassemia ) , were excluded in our patient based on serum electrophoresis and absence of target cells in peripheral blood smear . absence of anemia , microcytosis , and sickling crisis in the follow - up was consistent with sickle cell trait . our patient had several crises , like acute pancreatitis in pretransplant period and spontaneous closure of arteriovenous fistula and acute patchy cortical necrosis in immediate post - transplant period . such complications could be related or primed by her sickle cell trait . patchy cortical necrosis causing allograft dysfunction is an uncommon complication , more so in sickle cell trait patient . it was related to cyclosporine - basiliximab interaction following renal transplantation , which resulted in high cyclosporine levels . the raised level of cyclosporine was considered to be the primary event rather than related to renal dysfunction because of known drug interaction of cyclosporine with il-2 receptor blocker basiliximab . our success in re - introducing low - dose cyclosporine suggests its long - term safety in this setting . normal graft function even after 72-month follow - up is reassuring despite contrary reports in literature about poor outcome of such histopathological lesion . though cyclosporine nephrotoxicity leading to acute graft dysfunction is well known , the role of cyclosporine in producing patchy cortical necrosis is not reported . cyclosporine upregulates angiotensin-2 receptor and calcium responses in human vascular smooth muscle cells , leading to intrarenal vasoconstriction which could theoretically explain ischemic nephrotoxicity like acute cortical necrosis and hypertension , which was evident in our case . basiliximab which was used as induction therapy potentiates this vasoconstrictive ischemic injury by increasing cyclosporine levels via cytochrome p 450 pathways , especially in first 10 days of post - transplant period . cyclosporine could be reintroduced cautiously in such patients without adverse effects at later date as was done for this patient with good medium - term outcome , though one would logically avoid it should the patient tolerate mmf or sirolimus . this report underlies the importance of being aware of such severe drug interaction in susceptible patients with renal injury risk . rcn after kidney transplantation can result from unusual situations , such as technical surgical problems , graft preservation technique , transplantation across abo incompatible blood groups , positive cytotoxic antibody crossmatch , and any other factor that can generate hyperacute rejection , thrombotic microangiopathy and prothrombotic state ( antiphospholipid syndrome ) , and drugs ( tacrolimus , thymoglobulin ) . such an early vascular complication ( arterial / venous thrombosis ) leading to graft loss / dysfunction remains a constant and devastating complication in 2% of transplantation patients and constitutes a small population of overall acute cortical necrosis ( 5.3% ) . we hypothesize the contribution of sickle cell trait as a co - contributor along with cyclosporine - basiliximab for cortical necrosis . this could be the possible first report of such serious association leading to a complication which could be prevented .

renal transplant recipients who have sickle cell disease are at risk of infection , recurrent graft disease , and sickling crisis that affects the long - term outcome . we report a patient of sickle cell trait who developed patchy cortical necrosis in the perioperative period but had a good long - term outcome . the renal cortical necrosis was presumed to be secondary to cyclosporine - basiliximab interaction in the backdrop of sickling trait . the patient additionally had spontaneous closure of vascular access and severe hypertension immediately following transplantation suggestive of vaso - occlusive crisis . cyclosporine and basiliximab drug interaction needs to be recognized and steps need to be taken in patients to avoid perioperative graft dysfunction .

the danish knee ligament reconstruction registry ( dkrr ) is a nationwide population - based clinical database that was established in 2005 . it has the purpose of monitoring and improving the quality of both primary and revision knee ligament reconstructions in denmark.1 in the dkrr , all primary and revision anterior cruciate ligament ( acl ) and posterior cruciate ligament reconstructions are recorded as well as collateral ligament and multiligament reconstructions . all private ( n=27 ) and public ( n=24 ) hospitals report to this register , and registration is compulsory by legislation ( https://www.retsinformation.dk/forms/r0710.aspx?id=173197&exp=1).1 the number of procedures registered in the database each year is ~2,500 and the first 9 years , in total , 22,775 procedures have been registered . the rate of completeness of registrations in the dkrr has ranged between 85% and 92% in the past years and 90% of all orthopedic departments contribute to the registry.2 the registration completeness is defined as the number of patients registered with acl reconstruction in both the dkkr and the danish national registry of patients , divided by the number of patients registered in the danish national registry of patients with acl reconstruction , in the same period , hence defines the quality of the registration . reconstruction of the acl is performed for restoration of knee stability in typically young , athletic , and active patients . in the age - group that mainly are prone to acl injuries ( 1540 years ) , the incidence of surgery is 85 per 100,000.3 approximately two - thirds of patients with acl injury are treated surgically with acl reconstruction . injuries and reconstruction of other knee ligaments , the posterior cruciate ligament and collateral ligaments are more rare and constitutes < 10% of the all knee ligament reconstructions.1 hence , detailed preoperative , intraoperative , and 1-year follow - up data are recorded by the operating surgeon using a standardized form and a secured internet portal.1 the anamnestic data recorded preoperatively include the unique ten - digit personal identification number ( cpr number),4 sex , age , date of injury and surgery , previous surgeries to the affected knee , the cause of injury , objective ligament instability including instrumented anterior posterior laxity , and pivot shift test . the instrumented instability is measured by kt-1000 , kt-2000 , rolimeter , or other instrumented knee laxity evaluation ( table 1).1,5 the surgical - related data include : date of surgery , affected ligament , graft- and implant choice , operation technique , meniscal- and chondral damage and management , duration of surgery , complication to surgery , pharmacological antibiotic prophylaxis , and deep venous thrombosis prophylactics ( table 1 ) . quality of patient care and treatment outcomes is monitored using data from four quality indicators : completeness of 1-year follow - up data , usage of instrumented laxity measurements in preoperative diagnostics , knee laxity 1 year postoperative , and revision rate after 2 years.1,6 in relation to 1-year clinical follow - up , the following data are registered in the dkrr : rate of reoperations , cause of reoperation , pivot shift test , lachman test , collateral ligament laxity , and instrumented laxity test . further , the patients report independent subjective scores before surgery and at 1 , 5 , and 10 years after surgery.1 the functional subjective data of each patient is evaluated using the knee injury and osteoarthritis outcome score ( koos ) and tegner functional score.7,8 the koos is a knee - specific patient - reported outcome measure ( prom ) . in recent years , proms have gained increased interest as outcome measures and are now identified as important outcome measures after acl reconstruction.9 proms are collected via standardized questionnaires designed to measure underlying items that are not directly measurable , such as pain or daily activities . the koos consists of five subscores : sport and recreation , pain , quality of life , adl , and symptoms.7 these five subscores are evaluated separately . koos4 is a patient - reported outcome , computed from the four most responsive koos subscores , omitting adl.10 the tegner score was published in 1985 and is a sports - specific activity level score , which quantifies activity on a scale from 0 to 10 , with higher scores representing a higher level of activity.8 individuals competing in sports at an elite level have a tegner score of 10 , individuals participating in sports at a recreational level have a tegner score of 6 , and individuals on a disability pension due to knee problems have a score of 0 . data from the dkrr have been published in several international peer - reviewed journals ( table 2 ) . using the unique ten - digit cpr number assigned to all danish citizens at birth , it has been possible to do individual - based research linking data from the dkrr to other clinical and administrative databases , hence provide unique data on vital status , comorbidity , medical use , etc.4,11,12 since the cpr number is consistent through all danish registries , a precise individual - level data linkage between all danish registries is possible and hence the cpr number can be used to obtain complete individual follow - up on all patients and data - linkage on a personal level.4 most research on the registry has been on primary acl reconstructions2,1014 and only one paper to date is published on revision acl reconstruction and multiligament surgery ( table 2).15 the studies published on the dkrr have improved our knowledge of risk factors of sustaining operatively treated acl injury , information on comorbidity in acl reconstructed patients , and the failure rates and clinical outcome using different surgical techniques during acl reconstruction.1014 the results reported on the femoral tunnel drilling technique have triggered international discussions on the potential challenges and implications of initiating a new surgical technique.10 a study on the dkrr has also demonstrated that the dkrr enjoys an acceptable completeness of registration and a good registration of key variables although validation on objective measures , the koos and the tegner scores , needs further improvement and validation in the future.2 a study on oral contraception use and risk of acl injury in women indicates that the value of the dkrr may prove to be even greater than previously anticipated owing to the possibility of individual linkage to other important databases such as the danish national registry of patients and the national danish prescription database.12 this linkage gives us valuable information on drug use and comorbidity that can be used to investigate the implications of drug use and comorbidity in the future . these studies on the dkrr has improved our knowledge of acl injury and acl reconstructions and will hopefully lead to a better short- and long - term outcome for this group of young patients . furthermore , the studies have proven that the dkrr can reveal early associations of new treatments on the risk of sustaining revision surgery and instability of the knee . nevertheless , the mentioned studies do expose some of the weaknesses of national clinical databases such as the dkrr . one of the main weaknesses is the low response rate of objective and prom follow - up data , and the lack of radiological data to track osteoarthritis development . the database is managed by a steering committee consisting of surgeons and national organization members who geographically represent the country . centre for clinical epidemiology and biostatistics , north , department of clinical epidemiology , aarhus university hospital , aarhus , denmark , is responsible for the epidemiological and biostatistical support . the competence centre for clinical quality and health informatics provides the consultancy function for the databases . the dkrr is also supported by the danish regions in relation to development of quality and health informatics . the data are available for research and interested researchers can apply to the steering committee for relevant data . the dkrr provides an annual web - based report not only on the individual hospitals but also on national data , and a steering committee is responsible for optimizing and the management of the database . the competence center for clinical quality and health information performs the data management and epidemiological validation of report . this paper describes the content of the dkrr and the results from the database after the first 9 years , the numerous possibilities , and future perspectives .

the danish knee ligament reconstruction registry was established in 2005 as a web - based nationwide clinical database with the purpose of improving the monitoring and quality of both primary and revision knee ligament reconstructions in denmark . all primary and revision anterior and posterior cruciate ligament reconstructions as well as collateral ligament and multiligament reconstructions are recorded . main variables include sex , age , cause of injury , objective ligament instability , and surgical data , such as affected ligament , graft- and implant choice , operation technique among other things . the operating surgeon prospectively collects the data . hence , detailed preoperative , intraoperative , and 1-year follow - up data are recorded by the operating surgeon using a standardized form and a secured internet portal . the number of procedures registered in the database each year is ~2,500 and the first 9 years , in total , 22,775 procedures have been registered . since the beginning of the database multiple papers have been published in international peer - reviewed journals , improving the knowledge of patients treated with knee ligament reconstruction surgery . this paper reviews the content , organization , and published research from the danish knee ligament reconstruction registry .

with the wide use of immunophenotyping technology in clinic , acute mixed - lineage leukemia ( amll ) has been gradually recognized and established as a rare type of leukemia in recent years . it is characterized by existence of acute myeloid and lymphoid cells at the same time in the acute leukemia , and involved with lymphoid and myeloid cells as a dual character . european group for the immunological characterization of leukemia ( egil ) has proposed a scoring system for the immunological classification of acute leukemia . according to characteristics of leukemia cells regarding antigen expression and cell source , amll phenotype can be further divided into biphenotypic , bilinear and biclonal types ( including the conversion - type ) . also , other researchers have advised morphological and cell chemistry characteristics to support anll of amll calling ly+anll or my+all . but in fact , the diagnosis of amll is very difficult , and its clinical significance and prognosis is not entirely clear . therefore , the clinical data of 14 cases of amll children admitted to our hospital during nearly 10 years were analyzed and the results are reported in the following . subjects : from january 2000 to july 2009 , 14 cases of amll children were selected by morphological and immunophenotyping methods from 185 cases of childhood acute leukemia ( al ) admitted to the department of pediatrics , tongji hospital , tongji medical college of science and technology of huazhong university . there were 12 males and 2 females ; ages of patients were 1.512.0 ( mean 7 ) years . bone marrow morphology examinations : bone marrow smears were analyzed by wright 's classification counts , and had staining examinations , including inhibition test ( nse and naf ) for increase of non - specific esterase by peroxides ( pox ) and sodium fluoride , neutrophil alkaline phosphate staining ( nap ) and glycogen staining ( pas ) referenced to fab criteria to determine the types . immunophenotyping : bone marrow or peripheral blood ( 50ul ) were detected by fluorescent isothiocyanate ( fitc ) / phycoerythrin ( pe ) / peritoneum chlorophyll protein ( pre - cp ) labeled antibodies , ( all purchased from becton dickinson company ) which were added to the 20 l reaction tube , and 4c response for 2030 min ; then added 2 ml erythrocyte lysine , at room temperature 10min after staining ; pbs were washed 3 times , then added 0.5 ml pbs . all the samples were measured using facscan model flow cytometer ( bd usa co ) by the 488 nm laser light . each tube was revised to accommodate to 10000 cells via the standard calibration of fluorescent micro sphere by calibration instruments . cellquest software was used for analysis . in virtue of cd45/ssc gating naive to discerning leukemia cells , the positive expression rate of hematopoietic cell antigens was analyzed to calculate the immature cells . the monoclonal antibodies of b lineage include cd10 , cd19 , cd20 , cd22 ; t lineage include cd3 , cd5 , cd7 ; myeloid antigens include cd13 , cd33 , cd14 , cd15 ; while stem cell antigen markers included cd34 and hla - dr . chromosome analysis : bone marrow specimens with heparin and phytohemagglutinin were cultured for 24 h. the r - banding was used by the heated method of ( 87.5c ) ( wright staining ) , and the karyotype was analyzed by the international human genetics nomenclature . the bone marrow fluid mononuclear cells were separated by ficoll liquid and fusion gene detected by reverse transcription - polymerase chain reaction ( rt - pcr ) . clinical features : fourteen cases of childhood amll from 185 al cases accounted for 7.57% . two ( 71.43% ) female cases had clinical manifestation of fever , in 9 ( 64.29% ) cases enlargement of superficial lymph nodes was found , 12 ( 85.71% ) cases had hepatomegaly , 5 ( 35.71% ) cases splenomegaly ; 5 cases gum or skin bleeding . white blood cell count in 14 cases was ( 166.51.34)10/l , in 8 cases normal , and in 2 cases more than 100109/l with a mean count 31.010/l . g / l ( 37102 g / l ) and the average platelet count was 80.1410/l ( 0 - 318 ) 10/l , while in 7 cases it was below 5010/l . fab morphology typing of bone marrow cells : in 4 cases , 1 case was l1 , and 3 cases l2 ; acute non - lymphoblastic leukemia ( anll ) were 6 cases , including 3 cases of acute myeloid leukemia ( m2 ) , 2 cases of acute monotypic leukemia ( m5 ) , and 1 case of acute myeloid - monastic leukemia ( m4 ) . other 4 cases were diagnosed as amll on the morphology only . in 14 cases bone marrow consisted of 36.8% to 99.9% ( average 73.73% ) blast cells . this showed that 8 cases were of b - ly+/my+ biphenotypic , 2 cases of t - ly+/my+ biphenotypic , and 4 cases of t+b - ly+/my+ biphenotypic type . 8 cases had double expression of myeloid and b lineage and 4 cases t+b - ly+/my+ biphenotypic . in b antigens , 8 cases had cd19 positive expression , 3 cases cd10 positive , and 2 cases cd22 positive . the expression of myeloid and t lineage was in 2 cases and co - expression of t+b - ly+/my+ in 4 cases . positive expression of cd7 was seen in all the cases , and 4 cases of cd3 positive expression , 3 cases of cd5 expression . myeloid antigen expression was positive in the 14 cases , in which there were 7 cases of cd13 positive expression , 6 cases of cd14 positive expression , 5 cases of cd33 positive expression , and 2 cases of cd15 positive expression . cd34 positive expression was seen in 2 cases and hla - dr positive expression in 7 cases . chromosomes and fusion gene : six cases were analyzed in amll chromosomes and fusion gene . 2 cases were found abnormal in number of chromosomes , 1 case of hyper diploid . 4 cases were found with structural abnormalities , 2 cases of chromosome translocation , 1 case of centric chromosome breakage and 1 case of mixed anomalies . five cases were examined for fusion gene , 3 cases had abnormal amlex5/eto , aml - eto , mll gene rearrangements . chemotherapy and sequelae : because of no enough income of their parents , 5 cases did not receive chemotherapy , and 9 cases received chemotherapy as the only treatment . five cases received vdlp ( vincristine , daunorubicin , l - asparagine and dexamethasone ) in the first course . 3 cases received da ( daunorubicin , ara - c ) , dae ( daunorubicin , cytarabine , etoposide ) , and arta ( all - trans retinoic acid ) + dae respectively . after the first course of chemotherapy , 6 cases achieved cr and 2 cases did not complete the chemotherapy , 1 case missing cr . in 6 cases of cr , 5 cases were b - ly+/my + biphenotypic leukemia , 1 case t - ly+/my+ biphenotypic leukemia . now ( after 2 - 9 years follow up ) 6 cases who achieved complete remission are alive . amll is a rare kind of acute leukemia involved with myeloid cell lines and lymphoid cell lines . amll was not the same as ly+aml and my+all , which was produced with unique clinical and biological characteristics . the incidence of amll is reported 1% to 7% of acute leukemia , and some report even more than 20% . the incidence of amll in our series was 7.57% , which is in agreement with the literature . the cellular morphology of amll was aml and aml - m2 was the most encountered type , while m4 and m5 were rare . when the cellular performance of amll was all , l2 was the most observed leukemia . in our patients , 3 cases were aml m2 , accounting for 50% ; 3 cases were all - l2 , accounting for 75% , which is in accordance with the literature . the common clinical characteristics of amll were older age , higher count of white blood cell , obvious anemia , bone pain , enlarged spleen and lymph nodes , and infiltration of central nervous system and kidney . however , the clinical features of amll in our series were not consistent with the above reports , which could be because of the younger age of our patients . the morphology of amll was mostly illegible , to be misdiagnosed as aml or all . in recent years , with the wide application of flow cytometry , immunophenotyping has been the principal factor to diagnose the amll . according to different lineages , amll can be divided into three types : ( 1 ) biphenotypic type : the expression of myeloid antigen and lymphoid antigen in bone marrow ; ( 2 ) biclonal type ; ( 3 ) bilineal type . lee et al reported 18 cases of amll , with b / m in 14 cases , t / m in 3 , and t / b in 1 case . cycd22 , cd10 , cd19 , cd2 , cd3 , cd7 , cd33 and cd13 , had the highest antigen expression while early antigens of cd34 and hla - dr were also expressed . the children in our series were all pairs of phenotype b - ly+/my+ biphenotypic in 8 cases , t - ly+/my+ biphenotypic in 2 cases , and t+b - ly+/my+ biphenotypic in 4 cases . in 14 amll cases , cd13 and cd14 had the highest expression of myeloid immune phenotype . of the 14 cases , 2 cases had positive expression of hematopoietic stem cell marker cd34 antigen and 7 cases had expression of hla - dr , which is consistent with those reported in the literature . cytogenetic changes of childhood leukemia are recognized as an independent prognostic factor , so more recent researches have studied childhood amll cytogenetic characteristics . the majority confirmed that 60% to 80% of cases had cloned chromosomal abnormalities in amll . sub diploid , hyper diploid , partial trisomy and the monomer body were abnormal chromosomes . in this series , 2 cases had abnormal chromosome numbers as hyper diploids , with del ( 15 ) in each one separately . structural chromosome abnormalities t(9 ; 22 ) , t(l ; 9 ) , t(9 ; 11 ) , t(6 ; 14 ) , t(8 ; 21 ) , inv(16 ) , t(9 ; 22 ) and t(9 ; 11 ) are more common . the abnormal structures in this series were t ( 9 ; 22 ) , inv(16 ) , t(1 , 22)(q44 , q13 ) , t(8 , 21)(q2 , q22 ) , in 3 cases . as we know there are many amll cases of the 11q23 abnormal chromosome structures causing mll genetic changes . in addition , the emergence of ph chromosome is bound to affect the abnormal expression of abl gene . ph chromosome and mll gene rearrangements are the two poor prognostic factors . for the higher probability of ph chromosome and mll in amll , cytogenesis and molecular genetics could also explain the poorer prognosis of amll . but the biomarkers of amll in chromosomes and genetic abnormalities have not been found . in our patients , fusion genes were detected in 5 cases , and the positive results were amlex5/eto , aml - eto - positive and mll gene rearrangements . at present , many studies have reported the treatment of amll with various outcomes . faber and armstrong reported that cr rate of amll was 16.67% , while legrands was 47.0% and both were lower than the cr rate of aml ( 62% ) and all ( 82% ) at the same period significantly . in this article , 9 cases have received the treatment of amll , 4 cases were given the regimen of anll and 5 cases received all chemotherapy . after the first course of treatment , 6 patients have achieved cr ; cr rate was 66.67% , which was lower than zhengs report ( 75% ) . the reason may be related to younger age of the patients , and fewer numbers of observed cases during this short time . although there were many questions in the diagnosis and treatment of amll , these results of the study provide a basis for prevention and treatment of amll in children . to improve the diagnosis and treatment of amll , it is necessary that more researchers should collaborate and exchange their views .

objectiveacute mixed - lineage leukemia ( amll ) is characterized as the acute leukemia involved with acute myeloid cells and lymphoid cells at the same time . the amll is easily misdiagnosed because of a dual character involved with lymphoid and myeloid cells . at present , researches of amll in adults are more common . only some are reported for children . therefore , our aim was to study clinical characteristics of the childhood amll.methodsfrom january 2000 to july 2009 , 14 cases of amll children were selected by morphological and immunophenotyping methods from 185 cases of childhood acute leukemia admitted to the department of pediatrics , tongji hospital , tongji medical college of science and technology of huazhong university . medical records of all amll cases were reviewed for clinical characteristics.findingsfourteen cases of amll were screened from 185 cases of acute leukemia by morphology , immunology , cytogenetics and molecular ( micm ) . the rate of childhood amll accounted for 7.57% of pediatric acute leukemia ( al ) diagnosed in the research period ; white blood cell count in most of the patients was normal , the average value being 31.0109/l in the first visit . in the 14 cases of amll , 8 cases were b - ly+/my+ , 2 cases were t - ly+/my+b , and 4 were t+b - ly+/my+ . among them , nine cases received treatment . consequently , 6 cases reached complete remission ( cr ) ; 1 case had not complete remission ; 2 cases did not complete the treatment.conclusionthe diagnosis of amll should depend on the comprehensive evaluation of micm . as there are still many problems concerning amll , it is very necessary that the research units collaborate with each other to improve the prognosis of childhood amll . the limitations and applications of the results are that they are only based on the patients of one hospital .

this could be partly because of the racial predilection as a large percentage of the population has curly hair and also may be due to local cultural customs which unlike the west do not encourage daily shaving of facial hair . twenty - four consecutive male patients presenting to a university health center over a 1 year period from january 2014 to january 2015 with a clinical diagnosis of pseudofolliculitis involving beard area and not on any active treatment for the same were included in the study . patient with other associated skin conditions which according to the investigators might affect clinical feature and/or management including , but not limited to , acne vulgaris , seborrheic dermatitis , rosacea , and other forms of folliculitis were excluded from the study . patient history with regards to shaving habits , patient hair type , morphological patterns of the skin lesions , and dermoscopic findings were recorded . dermoscopic images were shown to the patients and the condition and the principles of treatment were explained to them using the dermoscopic images . most of the patients had a usual shaving frequency of 2 or less per week . all the patients who were using razors mentioned that they tended to stretch the skin while shaving . the most common dermoscopic findings included - handle bar sign showing curved hair attached to the skin on both ends [ figure 1 ] , white areas ( possibly indicating fibrosis ) and scaling [ figure 2 ] , underlying linear bluish pigmentation ( indicating the buried hair shaft ) [ figure 3 ] , and linear vessels with occasional areas of hemorrhage [ figure 4 ] . aerobic culture of specimens taken from the skin lesions showed positivity for staphylococcus epidermidis in eight of the case . sign showing curved hair attached to the skin on both ends white areas ( possibly indicating fibrosis ) and scaling underlying linear bluish pigmentation ( indicating the buried hair shaft ) linear vessels with occasional areas of hemorrhage there are very few studies which have tried to elucidate the dermoscopic correlates of pseudofolliculitis barbae . the first case report was from chuh and zawar , who used dermoscopy to demonstrate the ingrown hairs and also suggested that showing the dermoscopy image to the patients can help them understand the condition better and thus help in achieving better compliance and treatment results . described a unique dermoscopic feature of pseudofolliculitis barbae in the form of a solitary gray - blue , thick curved line and adjacent red lines set upon a structure - less pattern . this pattern does not correspond to known dermoscopic entities such as basal cell carcinoma and seborrheic keratosis . according to the authors , the solitary gray - blue , thick curved line corresponds to the edge of the tightly coiled cluster of ingrown hairs in the dermis and the red lines could represent aberrant vessels secondary to the inflammatory reaction . the gray and blue colors could be explained by the tyndall effect due the melanin in the pigmented hair shaft in the dermis . puhan and sahu recently reported a case of pseudofolliculitis over the back of a patient . pseudofolliculitis corporis for this condition which in this case was most probably induced by the effect of friction due to a pillow which the patient used to put behind is back while driving . our study showed that the most common pattern seen in all cases was the curved hair attached at both ends what we would like to label as the handle bar . white areas with scaling , underlying linear bluish pigmentation ( indicating the buried hair shaft ) similar to that described by ladizinski et al . , and linear vessels with occasional areas of hemorrhage were the other common dermoscopic patterns seen in our cases . other studies have highlighted the predisposition of african race and curly hair to develop pseudofolliculitis . another study showed that the ala12thr polymorphism of keratin k6hf of hair follicle may be partially responsible for the phenotypic expression . the racial and genetic factors might be important for explaining the high incidence of pseudofolliculitis in the population of our study . while we did not do a formal evaluation as done by chuh and zawar to see if showing the dermoscopy images helped patient compliance , as done by us we feel that in general the patients had a clearer understand of the problem and the principles of treatment after they were shown the dermoscopy images . dermoscopy shows characteristic features and can be a useful adjunct for diagnosis in pseudofolliculitis . stretching the skin while using razors and growing the facial hair to a point where it has the length to curve might be important risk factors in the development of pseudofolliculitis .

background : pseudofolliculitis of the beard area is a very common dermatological problem in our geographical region . this could be partly because of the racial predilection as a large percentage of the population has curly hair and also may be due to local cultural customs , unlike the west do not encourage daily shaving of facial hair.objectives:we aimed to mainly study the dermoscopic features of cases presenting with pseudofolliculitis . secondary objectives included evaluating clinical patterns and possible etiological factors.methods:twenty-four consecutive male patients presenting to a university health center with a clinical diagnosis of pseudofolliculitis involving beard area were included in the study . patient history with regards to shaving habits , patient hair type , morphological patterns of the skin lesions , and dermoscopic findings were recorded.results:majority of the patients had curly hair . most of the patients had a usual shaving frequency of 2 or less per week . all the patients who were using razors mentioned that they tended to stretch the skin while shaving . the most common dermoscopic findings included - handle bar sign showing curved hair attached to the skin on both ends , white areas indicate fibrosis and scaling , underlying linear bluish pigmentation ( indicating the buried hair shaft ) , and linear vessels with occasional areas of hemorrhage.conclusion:dermoscopy can be a useful adjunct for diagnosis and patient counseling in pseudofolliculitis . stretching the skin while using razors and growing the facial hair to a point where it has the length to curve might be important risk factors in the development of pseudofolliculitis.limitations:the lack of histopathological correlation is the main limitation in our study .

in the past decade or so , the remarkable advancement of dna sequencing technology and application has led to an astronomical accumulation of genomic data . this is especially true for the prokaryotic genomes as individual of them is only a few megabases in size . it is expected that in the next decade or two , there will be more data collected than what we can actually handle . therefore , database construction , improvement , and consolidation , as well as new tool development , are especially welcome . in this way , the sibling fields of genomics , such as pangenomics and metagenomics , can all be ready for curating , sharing , and mining floods of the incoming genomic big data . coming back to the reality and focusing on pangenomics , there were , as of december 2014 , more than 40 bacterial species that have over 20 fully - assembled genomes from different strains and isolates , allowing for comprehensive pangenomic studies . , which is defined as the entire genomic repertoire of a given species or phylogenetic clade when multiple species are defined by systematics . according to the definition , gene profile ( content ) of a pangenome is divided into three groups : core ( shared by all genomes ) , dispensable , and strain- ( or isolate- ) specific genes . a series of pangenomic studies have been performed in genomic dynamics [ 36 ] , pathogenesis and drug resistance [ 79 ] , bacterial toxins , and species evolution . the concept has also been extended to viral , plant [ 1315 ] , and fungal genome studies . a review on ten - year history and field achievement of pangenomics has just been published at the beginning of 2014 , which detailed major projects as well as methodology and technology advancements . here , we provide a brief review on the pangenomic software packages and tools , including their basic function , general utility , and popularity based on their cumulative citation by peer - reviewed scientific publications . although such a single - criterion evaluation may never be adequate and thorough , we hope that it provides a field guide for students and young scientists to make the right choice for their preferred applications . since 2010 , we have seen a dozen or so software packages and tools being put forward , which are capable of clustering orthologous genes , identifying single nucleotide polymorphisms ( snps ) , constructing phylogenies , and profiling core / shared / isolate - specific genes . although they may share similar functions , each has its own characteristics and limitations , leaving rooms for further improvement . among the early - developed packages , panseq and pancghweb were published in 2010 , followed by camber and the prokaryotic - genome analysis tool ( pgat ) in 2011 . it enables users to group genes into orthologs and to construct gene - based phylogenies of related strains and isolates . however , this package is rather specific for handling microarray data but not rna - seq data . panseq , another online pangenomic tool , is able to determine core and accessory regions of genome assemblies based on mummer and blastn , as well as to identify snps among the core genomic regions . in addition , panseq also has a locus selector module that selects the most discriminatory loci among the accessory loci or core gene snps . panseq , however , is not able to provide pangenomic profile and functional enrichment analysis that is important for the biologists to filter out functional relevance of the pangenomic elements . the later released camber is designed to identify multi - gene families from multiple bacterial strains and isolates . these multi - gene families can be used for sequencing error detection , mutation identification , and pangenomic profile computation . camber is supreme in refining gene function prediction according to multi - gene family information , but it does not provide tools for comparative or evolutionary analysis among strains and isolates . as a web - based database , pgat integrates several useful functions , such as plotting the presence and absence of genes among members of a pangenome , identifying snps among orthologs and syntenic regions , comparing gene orders among different strains and isolates , providing kegg pathway analysis tools , and searching for genes through different annotations such as the cluster of orthologous groups of proteins ( cog ) , psort , signalp , the tied mixture hidden markov model ( tmhmm ) , and pfam . however , pgat is just a database with a limited number of species curated and it can not perform analysis for new sequencing data from users . pgap is a stand - alone program developed by zhao et al . in 2012 , which contains five functional models . based on functional gene clustering and analysis , pgap presents pangenomic profile ( partitions of pangenomic elements or gene categories ) , genetic variation , species evolution , and function enrichment of different strains and isolates of a given pangenome . in addition , all analyses are performed with a single command , and such integration is rather user - friendly and efficient . nonetheless , pgap has its limitation as well . for instance , all its output files of the five models are text files , which lacks of intuitiveness . subsequently proposed a program called get_homologues in 2013 , which is also a versatile software package for pangenomics . this software package integrated data download , sequence feature extraction , homologous gene identification , pangenome profiling , graphical display , and phylogenetic tree construction into one powerful toolkit . several other tools were also available in 2013 , such as pancake and pannotator . pancake was developed for identifying singletons and core regions in arbitrary sequence sets , while pannotator , a web - based automated pipeline , was designed for the annotation of closely - related genomes for pangenomic analysis . however , these two tools only focus on simple functions , such as clustering homologous genes and gene curation . in 2014 , a powerful and flexible toolkit , the integrated toolkit for exploration of microbial pan - genomes ( itep ) , was published by benedict and colleagues . itep integrates plenty of existing bioinformatics tools for pangenomic analysis , including protein family prediction , ortholog detection , functional domain analysis , pangenomic profiling , and metabolic network integration . moreover , itep also integrates some visualization scripts that assist biologists in phylogenetic tree construction , annotation curation , and specific query for conserved protein domain identification . in 2014 , another rapid core - genome alignment and visualization pangenomic software package , harvest , was proposed by treangen et al . harvest contains tools , such as parsnp and gingr , for core gene alignment , variant calling , recombination detection , and phylogenetic trees construction . to analyze pangenomic profile in a larger scale , a software package pangp was developed with a graphic interface by zhao et al . in 2014 . spine and agent were also developed in 2014 , which are capable of profiling pangenomes based on both finished and draft genomic sequences . we summarized all the software packages and tools in table 1 , highlighting their platforms and major features . we went one step further and ranked them according to their citations by peer - reviewed scientific publications ( figure 1 ) , which were collected from isi web of science - science citation index expanded . our summary indicates that panseq and pgap have been the most popular packages up to the end of 2014 . although single - tool solution could not usually satisfy the need for understanding the whole picture , a wish list from the users is always helpful for prioritizing goals for the package developers , hence providing directions for improving each package . first , the performance of pangenomic analysis strongly depends on the accuracy of genome assembly and annotation . therefore , an adequate number of complete sequence assemblies are a prerequisite . currently , most of the existing bacterial genome sequences are actually incomplete ( in most of the cases , contigs are not joined together into single chromosomes ) , and some only have high - quality and high - coverage raw data available . the inclusion of incomplete genome assemblies for pangenomic analysis may need scaffold building that requires reformatting of the contig data files . despite the development of the third - generation sequencing technology , which would certainly help the assembly and finishing of prokaryotic genomes , incomplete prokaryotic genomes are expected to be deposited into public databases in mass . it would be a waste if such data are left unused . second , orthologous gene identification is a key step in pangenomic analysis . at present , the existing software for ortholog detection is mainly based on sequence similarity , phylogenetic relationship , or other annotation information such as functional information . the development of novel and more efficient ortholog identification method for multiple closely - related strains and isolates can greatly improve the accuracy of pangenomic analysis . one possibility is to integrate gene gain - and - loss information for phylogeny building among strains and isolates . the other is how to implement a filter that differentiates more diverse strains or isolates from the less diverse for pangenomic analysis . for instance , if we choose all genomes of a species for an analysis , which include one or a few divergent genomes , the core genome will be much shorter or reduced . obviously , individual genomes should be selected and regrouped for better representation of average nucleotide identity ( ani ) . therefore , for a better pangenomic analysis , detailed information for the available samples is of essence , which should include their genotypes , phenotypes , and habitats . fourth , the current tools have not incorporated some recent advancements in prokaryotic genomics , such as the so - called genome - organization frameworks ( gofs ) , which are not only unique to each species but also provide guidance for sequence assembly and finishing . other annotation information , such as that of non - coding rnas , pseudogenes , and epigenetic elements , remains to be implemented into the relevant software packages . finally , a never - ending improvement of pangenomic tools is visualization that provides not only better displays but also quality graphics for publication . we provide an overview on the existing pangenomic analysis tools and hope to see improvements of the software tools from their original developers . we certainly express our enthusiasm for new tools to join the competition , and after all , for a piece of bioinformatic work , a database or a toolkit , the survival or winning game is in its long - term maintenance and constant improvement .

since the proposal for pangenomic study , there have been a dozen software tools actively in use for pangenomic analysis . by the end of 2014 , panseq and the pan - genomes analysis pipeline ( pgap ) ranked as the top two most popular packages according to cumulative citations of peer - reviewed scientific publications . the functions of the software packages and tools , albeit variable among them , include categorizing orthologous genes , calculating pangenomic profiles , integrating gene annotations , and constructing phylogenies . as epigenomic elements are being gradually revealed in prokaryotes , it is expected that pangenomic databases and toolkits have to be extended to handle information of detailed functional annotations for genes and non - protein - coding sequences including non - coding rnas , insertion elements , and conserved structural elements . to develop better bioinformatic tools , user feedback and integration of novel features are both of essence .

scrub typhus is an acute febrile illness characterized by fever , chills , myalgia , skin rash , lymphadenopathy , and an eschar at the site of the inoculating chigger bite . scrub typhus , rickettsial infection ( orientia tsutsugamushi ) , is transmitted by trombiculid chigger mites ( leptotrombidium species ) . it is endemic in southern and eastern asia including northern australia , and the western pacific islands , . the spectrum of the clinical severity of scrub typhus ranges from mild to severe with fatal complications such as meningoencephalitis , pneumonitis , acute respiratory distress syndrome , acute kidney injury ( aki ) , myocarditis , disseminated intravascular coagulation ( dic ) , and septic shock , , , . the reported incidence of renal failure caused by scrub typhus varies from 10.5% to 42.6% according to the criteria of renal failure , . in most case reports , the serum creatinine level was restored after the administration of appropriate antibiotics such as doxycycline and azithromycin although varying degrees of renal deterioration and recovery time have been reported . to the best of our knowledge , no case of progression to end - stage renal disease has been reported for this condition . a 71-year - old man was transferred to our university hospital from a private clinic because of significantly elevated serum creatinine . his serum creatinine level had been 1.2 mg / dl in the health screening examination performed 6 months prior to admission . his past medical history included diabetes mellitus for 10 years treated with oral hypoglycemic agents . the patient reported climbing mountains in the jeolla province of korea , 2 weeks prior to admission to our hospital . the serum creatinine level was 11.0 mg / dl as measured at a private clinic , and the patient was transferred immediately to soonchunhyang university cheonan hospital . at the time of admission , vital signs were as follows : blood pressure , 170/90 mmhg ; pulse rate , 87 beats / min ; body temperature , 36.4c ; and respiratory rate , 20 breaths / min . the patient 's mental status was alert . on physical examination , an eschar , which is characteristic of scrub typhus , was observed on the right arm near the axillary area . complete blood cell counts were as follows : white blood cell count , 8.9610/l ; hemoglobin , 10.9 g / dl ; hematocrit , 31.5% ; and platelet count , 21710/l . the results of arterial blood analysis were : ph , 7.31 ; arterial co2 tension , 25 mmhg ; arterial o2 tension , 90 mmhg ; bicarbonate , 12.6 mm ; and o2 saturation , 96% . the biochemistry results were as follows : c - reactive protein ( crp ) , 78.54 mg / l ; blood urea nitrogen , 91.6 mg / dl ; creatinine , 14.1 mg / dl ; sodium , 133 meq / l ; potassium , 5.8 meq / l ; and chloride , 103 meq / l . other significant laboratory findings were as follows : total protein , 5.7 g / dl ; albumin , 3.1 g / dl ; aspartate transaminase , 50 iu / l ; alanine aminotransferase , 79 iu / l ; uric acid , 11.0 mg / dl ; creatinine phosphokinase , 128 iu / l ; and lactate dehydrogenase , 652 iu / l . microscopic urinalysis showed red blood cells > 100/high - power field ( hpf ) , white blood cells 5099/hpf , and cast<1/hpf . serologic tests were all negative for rheumatoid factor , antinuclear antibody , hepatitis b and c virus , human immunodeficiency virus antibody , and syphilis ( rapid plasma reagin test ) . the patient had a history of outdoor activities and showed typical clinical manifestations of scrub typhus , especially an eschar in the right axillary area . the results of an immunochromatographic antibody assay test for o. tsutsugamushi was positive , and the immunofluorescent antibody assay test profile showed an immunoglobulin ( ig)m titer>1:2048 and igg titer>1:2048 . doxycycline was administered 200 mg on the first day , followed by a maintenance dose of 100 mg once daily for 20 days . for correction of hyperkalaemia , metabolic acidosis , and marked elevation of serum creatinine levels with uremic symptoms , the patient was started on hemodialysis on the first day of admission . after emergency management , he was placed on hemodialysis three times / week with conservative treatment . clinically , the patient 's symptoms improved dramatically while he was receiving doxycycline , showing a gradual decrease in inflammatory markers such as crp we performed an ultrasonography - guided renal biopsy to rule out other underlying diseases , including diabetic nephropathy and primary glomerulonephritis , on day 7 after admission . 2 ) , and no signs of mesangial expansion or glomerulosclerosis , which are common in diabetic nephropathy , were observed . however , vascular changes such as intimal fibrous thickening and medial sclerosis were severe . the patient remained on hemodialysis three times / week , and he was discharged on day 25 after admission . we expected the patient to recover his renal function gradually , but he remained on hemodialysis in an artificial kidney room of a private clinic for 18 months after discharge , and an arteriovenous fistula was formed . the patient 's renal function did not improve , and his serum creatinine level remained at 810 mg / dl . in the present study , we describe a patient with renal failure caused by scrub typhus that did not show improvement of renal function despite a decrease in the levels of inflammatory markers such as crp . although case reports of patients with renal failure caused by scrub who underwent renal biopsy are rare , the presence of o. tsutsugamushi coccobacilli in the renal tubule has been reported previously . in our patient , although the pathophysiology of renal failure as a complication of scrub typhus has not been fully elucidated , there are several possible hypotheses . first , because the basic pathologic characteristic of scrub typhus is multiorgan vasculitis of the small blood vessels , renal failure can be assumed to be associated with vasculitis , . a third explanation is prerenal azotemia caused by renal hypoperfusion associated with shock or volume depletion , . the effective renal blood flow decreases with increased vascular permeability , and this change is associated with systemic vasculitis . in addition , other nonspecific symptoms such as nausea , vomiting , poor oral intake , and diarrhea can be aggravated by volume depletion . however , in the present patient , there were no clinical and/or laboratory or histopathologic findings suggestive of vasculitis , dic , or renal hypoperfusion . finally , tubulointerstitial nephritis caused by direct invasion of the renal parenchyma by the microorganism may cause renal failure . similar to our case , multifocal renal tubular necrosis and infiltration of inflammatory cells into the tubulointerstitium on renal biopsy were previously reported . because the patient was transferred from a private clinic , it is assumed that fluid therapy was performed to some extent . infection by o. tsutsugamushi under these conditions may explain why renal function was not fully recovered . serologic surveys of patients have confirmed the prevalence of spotted fever group rickettsioses , including japanese spotted fever . because the clinical symptoms and signs of japanese spotted fever are similar to those of scrub typhus , japanese spotted fever may be misdiagnosed as scrub typhus , . in our patient , the antibody titer for o. tsutsugamushi by immunofluorescent antibody assay was > 1:2048 and that for rickettsia japonica was 1:1280 . although this is difficult to determine exactly because the presence of microorganisms was not verified , superinfection is possible . furthermore , cross - reactions between r. japonica and o. tsutsugamushi have been reported although to a lesser extent than between r. japonica and typhus group rickettsia . finally , it is possible that the patient 's baseline renal function was not normal . the estimated glomerular filtration rate according to the cockroft gault equation and considering age , sex , and weight was 50 ml / minute 6 months prior to admission . in addition , severe vessel changes and mild tubular atrophy were observed in the biopsy specimen . according to the most recent report about renal failure due to scrub typhus , old age and underlying diseases such as hypertension , diabetes mellitus , and chronic kidney disease are predicting factor of aki , but there are no cases of end - stage renal disease . renal function of all patients was restored to the baseline after the administration of appropriate antibiotics . therefore , although the patient 's baseline renal function was slightly reduced , it is difficult to consider pre - existing renal dysfunction as a critical cause of permanent renal damage . renal failure caused by scrub typhus is commonly known to be reversible with the appropriate antibiotic therapy , and there are no reports of healthy adults requiring maintenance hemodialysis after scrub typhus infection .

renal failure caused by scrub typhus is known to be reversible . in most cases , renal function is almost fully restored after appropriate antibiotic treatment . a 71-year - old man was diagnosed with scrub typhus complicated by renal failure . a renal biopsy revealed histopathologic findings consistent with acute tubulointerstitial nephritis . renal function did not improve 18 months after discharge and the patient required continuous hemodialysis . although severe renal failure requiring dialysis is a rare complication of scrub typhus , we describe a case of scrub typhus requiring maintenance hemodialysis . to the best of our knowledge , this is the first such report .

the patient was a 10 year - old boy with a height of 128 cm and a weight of 36 kg who complained of pain in the right lower abdomen . he was diagnosed with appendicitis , and it was decided to do an appendectomy . he had been diagnosed with grade 3 mental retardation at age 4 although an exact diagnosis was not possible because a dna test was not done . however , the parents were planning for a second child and had a dna test done in england when the patient was 10 and confirmed an 8p23 deletion . according to the past history , there were no abnormalities that accompanied the genetic disorder such as asthma , and dna tests were done on the parents for a family history but all were normal . based on the physical exam , the patient exhibited the characteristic facial features of microcephaly with a broad nasal bridge , short neck , and high arched palate . according to the airway examination , the interincisional distance was approximately 3 cm and the thyromental distance was approximately 5 cm when the mouth was opened at its widest maximum . the mallampati airway classification was grade 3 and difficulty in intubation was predicted ; there were no limitations in neck movement and there were no loose teeth but they were irregular . in an echocardiography conducted at another hospital , the patient had no heart problems that can accompany 50% of the people with deletion 8p23 syndrome , and there were no indication of ebstein 's malformation and tof . no abnormalities were found in the blood tests or computed tomography ( ct ) done before surgery . the patient exhibited severe mental retardation and although simple communication was possible , he was not able to use language properly . the patient responded impulsively and showed destructive and aggressive behavior characteristic to this syndrome when moving to the operating bed such as pulling hair and kicking with his feet . blood pressure before anesthesia was 125/70 mmhg ; heart rate was 115 beats / min ; oxygen saturation was at 100% , and the ecg was normal . in the emergency room before coming up to the operating room , a 22 g intravenous access was prepared on the right upper extremity but no medication before anesthesia was administered . as intubation was predicted to be difficult , a video glidescope was additionally prepared as well as a mccoy laryngoscope . before proceeding with anesthesia , preoxygenation 50 g of fentanyl and 150 mg of pentothal sodium was iv injected and mask ventilation was started with 4.0 vol% sevoflurane and 100% oxygen . after checking that the mask ventilation was operating properly , 30 mg rocuronium bromide was administered for rapid sequence intubation while sellick 's maneuver was done due to the risk of respiratory aspiration . after a minute , proper muscle relaxation was verified and the glottis were exposed using a macintosh laryngoscope . grade 3 in cormack and lehane airway classification was confirmed , and although intubation of an endotracheal tube with 6.5 mm envelope was attempted , it was unsuccessful so the video glidescope was used to carefully intubate an endotracheal tube with inserted stylet . directly after intubation , blood pressure was 130/88 mmhg ; heart rate was 100 beats / min , and oxygen saturation was at 100% . mechanical ventilation was started with volume controlled ventilation with a 400 ml tidal volume and a respiratory rate of 15/min , while maintaining anesthesia with 50% oxygen / n2o and 1.0 - 2.0 vol% of sevoflurane . the operation lasted a total of 1 hour and 35 minutes and 200 ml of ringer 's lactate solution was supplied . there were no abnormalities during surgery and after the surgery had finished , 7.5 mg of pyridostigmine and 0.3 mg of glycopyrrolate was iv injected to contend with muscle relaxation . spontaneous respiration was induced to confirm stable respiration . after confirming that the tidal volume was more than 5 ml / kg , the patient responded to the command to open his eyes , which indicated that he was awake . then , extubation was done , followed by 100% oxygen through a mask while checking the recovery of consciousness and muscle motility . respiration was regular in the recovery room but the patient displayed excessive behavior and impulsive responses shown before the anesthesia so 4 mg of nalbupine was iv injected and he was stabilized . deletion 8p syndrome is a very rare congenital disease with characteristic cardiac malformation , mental retardation , craniofacial anomalies , malformations of the digestive system , and neural developmental abnormalities . it was first detailed in 1973 , and deletion 8p23 was first detailed in 1988 . large terminal deletions can be discovered through basic chromosome testing but the latest molecular biological methods such as fluorescence in situ testing ( fish testing ) or array comparative genomic hybridization ( array cgh ) need to be used to discover or confirm small interstitial deletions . the frequency of 8p23 deletion syndrome is equal regardless of gender and the age of the parents , and it appears as either a first occurrence in one family ( de novo ) or through familial translocation . there are cases where a parent has the 8p deletion but their children have no abnormalities , or parents have no deletion but the children develop problems . deletion 8p syndrome causes developmental delays in nearly all the organs in the body so it exhibits diverse clinical signs . the most important and common symptom is cardiac malformations and mild to moderate intellectual disabilities and mental retardation . also , due to microcephaly , the size of the brain is smaller which can lead to more problems , and there are common reports of behavioral abnormalities such as excessive behavior , impulsive responses , and attention deficit . destructive and aggressive behavior and abrupt changes in response are characteristic , and they express themselves to others through behaviors such as pulling hair , hitting , biting , and kicking with their feet . in boys , there could be cryptorchidism or hypospadia and they may need surgical correction . hypotonia or hypertonia or a combination of these can occur in newborns ; in ophthalmology , there could be strabismus , myopia , or hyperopia but can be corrected with ordinary glasses , and serrated teeth form can occur . it usually does not affect pregnancy but there is a high possibility of giving birth to small for gestational age ( sga ) or large for gestational age ( lga ) . the points to be considered in general anesthesia of patients with deletion 8p syndrome is that intubation will be difficult because of facial features such as microcephaly , a high arched palate , cleft palate , high narrow forehead , broad nasal bridge , short neck , and a large tongue ; congenital diaphragmatic hernia occurs in 20 - 30% of people with this syndrome but can be corrected through surgery , and esophageal motility disorder which leads to frequent gastroesophageal reflux so there is a high risk of aspirating stomach content resulting in aspiration pneumonia when inducing anesthesia or during recovery . therefore , the degree of difficulty in securing the patient 's airway should be checked beforehand , and the operator should be well - acquainted with the asa difficult airway algorithm . cornelia de lange syndrome ( cdls ) caused by mutation of the nipbl ( nipped - b like ) gene located at chromosome 5p13 is very similar to deletion 8p syndrome and has difficulties in intubation due to characteristic facial features , poor esophageal motility , and congenital diaphragmatic hernia and is easily exposed to aspiration . . failed in achieving an orotracheal intubation of a 8 year - old cdls patient with a cleft palate and tof so they used a laryngeal mask and bronchofiberscope to intubate , and fernandez - garcia et al . also did not use muscle relaxants in the general anesthesia of a 11 year - old cdls patient considering the difficulties in intubation and maintaining airway but successfully conducted anesthesia by using a laryngeal mask . conducted rapid sequence intubation using pentothal sodium and succinylcholine on a 9 year - old cdls patient undergoing surgery due to external injuries keeping in mind the possibility of aspiration and enterocleisis from malrotatio intestini . also in our case , there were no limitations in neck movement but intubation was anticipated to be difficult according to mallampati airway classification so video glidescope was prepared as well as a mccoy laryngoscope . in the first attempt , it was confirmed as a grade 3 cormack and lehane airway classification so a rapid sequence intubation using the video glidescope and sellick 's maneuver was done . a grade 3 cormack and lehane airway classification signifies that only the epiglottis is visible through proper use of the laryngoscope , and grade 4 is when no anatomical structure relevant to the airway but only soft tissue is visible . pre - anesthetic evaluation of deletion 8p syndrome patients can be very difficult because severe mental retardation and uncooperative behavioral disorders can make accurate examination and tests difficult . evaluation of cardiac function is essential in particular because there is the possibility of cardiac malformations . accompanying cardiac malformation such as avsd , ps , and vsd , ebstein 's malformation , tof , and hypoplastic left heart syndrome ( hlhs ) can congenitally occur . contended that from patients with deletion 8p23 syndrome , 75% of those with a terminal deletion and 94% of those with an interstitial deletion had cardiac malformation . in our case , an echocardiography was done as a pre - anesthetic evaluation to confirm that there were no cardiac malformations and cardiac output was also normal . in addition , since excessive behavior , impulsive responses , lack of cooperation , and self - injurious behavior from mental retardation can accompany most patients with deletion 8p syndrome , general anesthesia is preferred rather than regional anesthesia and occurrence of agitation in the recovery room must also be carefully observed and prevented . extubation is done after awakening because intubation is commonly difficult in patients with deletion 8p syndrome ; complications such as laryngospasm and coughing can emerge , and the risk of aspiration from gastroesophageal reflux is high . however if there is no evidence of gastroesophageal reflux and risk of aspiration in the pre - anesthetic evaluation , and intubation was not difficult , then extubation before awakening can be considered to reduce the excessive behavior and impulsive responses of the patient . the patient in our case showed pain and agitation after post - awakening extubation , and was stabilized by iv injecting of nalbuphine . in conclusion , there have been no anesthetic cases in korea of patients with deletion 8p syndrome and when a patient shows several characteristics mentioned here , pre - anesthetic evaluation of the patient such as assessing the degree of intubation difficulty according to facial deformities , cardiac malformation , and mental retardation must be thoroughly conducted to select a suitable method of anesthesia .

a deletion 8p syndrome is a relatively uncommon congenital disease characterized by mental retardation associated with multiple malformation that make anesthetic management a challenge . anesthetic management of a patient with deletion 8p syndrome may pose a serious problem mainly from difficult tracheal intubation , aspiration complication and cardiac malformation . we experienced a case of 10 year - old boy with a deletion 8p syndrome who underwent appendectomy under the general anesthesia . intubation was performed by video glidescope after unsuccessful attempt with macintosh laryngoscope . a high arched palate , short neck , poor patient cooperation due to mental retardation and occasional autistic behaviour made airway management difficult . this case should alert anesthesiologists to the greater difficulties of managing patients with deletion 8p syndrome .

the prevalence of obesity is increasing in poland and worldwide [ 1 , 2 ] . obese patients are predisposed to the early development of diabetes mellitus , hypertension , heart disease , and certain malignancies [ 2 , 3 ] . furthermore , obesity has been considered a potential risk factor for poor outcomes after surgical procedures [ 3 , 4 ] . according to the world health organization , overweight ( measured in kg / m ) is defined as body mass index ( bmi ) of 25 to 29.9 ; a bmi 30 to 34.9 is considered obese , and morbid obesity is defined as a bmi > 35 . morbidly obese patients often have greater incidences of perioperative complications and morbid obesity is considered by some authors to be a relative contraindication to laparoscopic surgery . the efficacy and morbidity of laparoscopic nephrectomy in obese patients were examined in few studies in comparison with the conventional open approach . some authors suggested surgery is more complicated in obese than in non - obese patients independent of the method of surgery , but laparoscopic access results in fewer complications in obese patients than the open approach [ 7 , 8 ] . retroperitoneal laparoscopic surgery may be more advantageous in the obese patient than transperitoneal laparoscopic surgery because of the large abdominal girth and the easier retroperitoneal access . however , at our institution , we favor the transperitoneal approach because of its familiarity with traditional anatomic landmarks . in this study we present two cases of laparoscopic radical nephrectomy due to renal tumors in extremely obese patients . a 54-year - old man was admitted to our department for surgical treatment of a left kidney tumor . in medical history , three months earlier , abdominal ultrasound was performed because the patient felt a presence in the left upper abdominal quadrant . patients data : height 176 cm , weight 130 kg ; bmi 42.44 ; asa class 3 ( fig . the patient was then qualified for laparoscopic radical left nephrectomy with the technique described below . a 49- year - old man was referred to clinic of urology also for surgical treatment of tumor in right kidney . the patient 's history revealed arterial hypertension , obesity , and appendectomy ( 40 yrs . ago ) . right kidney tumor was found incidentally during abdominal ultrasound performed due to intermittent abdominal pain . patients data : height 176 cm , weight 176 kg ; bmi 56.81 ; asa class 3 ( fig . the patient was then qualified for laparoscopic right radical nephrectomy using the technique described below . the procedure was performed in a transperitoneal fashion using four ports . to create a pneumoperitoneum we placed our ports in a cluster fashion in the ipsilateral upper quadrant ( fig . 3 ) with lateral shift such that the midline trocars were repositioned lateral to the abdominal rectus muscle . the first 10 mm umbilical trocar was inserted and pneumoperitoneum was achieved in a standard manner . three additional trocars ( 2 x 5 mm , 1 x 12 mm ) were inserted under direct vision : a 5 mm trocar halfway between the umbilicus and xiphoid in the midclavicular line , a 12 mm trocar below the umbilicus laterally to the edge of the rectus muscle , and another 5 mm trocar in the anterior axillary line below the costal margin . after the lower pole of the kidney was freed , the kidney covered by the perirenal fat and gerota 's fascia was moved laterally and the renal vessels were identified . once freely dissected , the renal artery was clipped and transected using titanium clips ( tfx medical ltd . , high wycombe , uk ) . the renal vein was secured by means of an endo - gia ( tyco healthcare group lp , norwalk , connecticut , usa ) stapling device . the lateral attachments were dissected to completely free up the kidney . the ureter was clipped and dissected as distally as possible ; the renal specimen was entrapped in an endocatch bag ( tyco healthcare uk ltd . , the 5-mm closed suction drain was left in the retroperitoneal space ; it was inserted through the port left by the lateral 5 mm trocar . specimens were removed intact without morcellation through a lengthened incision of the port site . in both cases , no temperature rise was noted postoperatively . the time to resume oral intake was two days in both cases . in both cases wounds , the drain left after the surgery ( left retroperitoneal space ) was removed on the 4 postoperative day ; while in the second case , the drain was removed on the 9 day . patients were discharged from the hospital on the sixth and fifth day after surgery in case 1 and 2 respectively . a 54-year - old man was admitted to our department for surgical treatment of a left kidney tumor . in medical history , three months earlier , abdominal ultrasound was performed because the patient felt a presence in the left upper abdominal quadrant . patients data : height 176 cm , weight 130 kg ; bmi 42.44 ; asa class 3 ( fig . the patient was then qualified for laparoscopic radical left nephrectomy with the technique described below . a 49- year - old man was referred to clinic of urology also for surgical treatment of tumor in right kidney . the patient 's history revealed arterial hypertension , obesity , and appendectomy ( 40 yrs . ago ) . right kidney tumor was found incidentally during abdominal ultrasound performed due to intermittent abdominal pain . patients data : height 176 cm , weight 176 kg ; bmi 56.81 ; asa class 3 ( fig . the patient was then qualified for laparoscopic right radical nephrectomy using the technique described below . the procedure was performed in a transperitoneal fashion using four ports . to create a pneumoperitoneum we placed our ports in a cluster fashion in the ipsilateral upper quadrant ( fig . 3 ) with lateral shift such that the midline trocars were repositioned lateral to the abdominal rectus muscle . the first 10 mm umbilical trocar was inserted and pneumoperitoneum was achieved in a standard manner . three additional trocars ( 2 x 5 mm , 1 x 12 mm ) were inserted under direct vision : a 5 mm trocar halfway between the umbilicus and xiphoid in the midclavicular line , a 12 mm trocar below the umbilicus laterally to the edge of the rectus muscle , and another 5 mm trocar in the anterior axillary line below the costal margin . after the lower pole of the kidney was freed , the kidney covered by the perirenal fat and gerota 's fascia was moved laterally and the renal vessels were identified . once freely dissected , the renal artery was clipped and transected using titanium clips ( tfx medical ltd . , high wycombe , uk ) . the renal vein was secured by means of an endo - gia ( tyco healthcare group lp , norwalk , connecticut , usa ) stapling device . using the liga - sure device ( tyco healthcare uk ltd . , the lateral attachments were dissected to completely free up the kidney . the ureter was clipped and dissected as distally as possible ; the renal specimen was entrapped in an endocatch bag ( tyco healthcare uk ltd . , the 5-mm closed suction drain was left in the retroperitoneal space ; it was inserted through the port left by the lateral 5 mm trocar . specimens were removed intact without morcellation through a lengthened incision of the port site . in both cases , no temperature rise was noted postoperatively . the time to resume oral intake was two days in both cases . in both cases wounds healed normally ( fig 2 , 3 ) . in case 1 , the drain left after the surgery ( left retroperitoneal space ) was removed on the 4 postoperative day ; while in the second case , the drain was removed on the 9 day . patients were discharged from the hospital on the sixth and fifth day after surgery in case 1 and 2 respectively . obesity has been considered by some as a relative contraindication to laparoscopic surgery because of the higher risk of complications . moreover , obese patients have more perioperative complications than non - obese patients regardless of the surgical method used and are at a greater risk of wound , pulmonary , and cardiovascular complications . laparoscopic surgery is appealing in obese patients because of lessened pulmonary restriction caused by pain , minimized wound complication , and early ambulation . technical challenges specific to laparoscopy in the obese patient included adequate insufflation of the peritoneal cavity , trocar insertion , maintenance and physiologic complications of the pneumoperitoneum and visualization due to limited exposure [ 8 , 12 ] . however , techniques , instrumentation , and knowledge of physiology associated with laparoscopic procedures are still improving . as a result of this progress , obese patients can undergo laparoscopic procedures safely with reduced patient morbidity , which was shown in some contemporary series . hedican and associates reported on 30 obese patients ( mean bmi 35.8 ) who underwent hand - assisted laparoscopic renal surgery , mostly for malignant disease . kapoor and coworkers compared the results of 23 transperitoneal laparoscopic procedures on morbidly obese patients with historic controls and found no significant differences in the number of complications . matin and associates compared 21 patients with a bmi > 30 who underwent laparoscopic renal or adrenal surgery with a historical cohort of comparable patients who previously had open surgery . the laparoscopic cohort had a 29% postoperative complication rate with four ( 19% ) major complications . this finding compared favorably with the open surgical cohort , where the authors experienced a 67% complication rate with seven ( 33% ) major complications . furthermore , the benefits of reduced analgesic use , shorter hospital stays , and faster convalescence favor performing endoscopic surgery in the obese population . the key alterations in the laparoscopic technique in morbidly obese patients include modifications in trocar positioning [ 7 , 8 , 10 , 12 ] . when patients are placed in the supine position , the anatomic landmarks are similar between obese and nonobese patients . however , when patients are placed in a modified flank position , the pannus in morbidly obese patients invariably shifts disproportionately ( the umbilicus relative to the midline ) ( fig . 4 ) . in consequence of this endocavital transposition , trocar placements at the level of the umbilicus will be below the level of the midline . a lateral shift accounts for this anatomic landmark displacement , but also compensates for the distance from the retroperitoneum as the peritoneum expands radially with insufflation . by placing the trocars laterally in the obese patients , the distance to the area of interest is reduced and visual obstruction by intra - abdominal contents is prevented . the decision to use a fourth trocar in our cases depended on intra - abdominal factors ( ie , liver , spleen , and bowel retraction ) and not obesity . modified flank position - trocar placement for non - obese ( a ) and obese ( b ) patients . in our opinion laparoscopic radical nephrectomy in morbidly obese patients is a feasible and safe procedure using minor technical modifications .

laparoscopic radical nephrectomy has been widely accepted as the preferred management of low stage renal masses . endoscopic management is advantageous for its reduction in perioperative and postoperative complications . in the mid-1990s , morbid obesity was considered a relative contraindication to laparoscopic technique . the authors present two cases of laparoscopic radical nephrectomy due to renal tumors in extremely obese patients . the aim of this study is not only to present the operative technique but also to show that the laparoscopic procedure is safe and effective in morbidly obese patients .

four different types of dendritic cells exist in lymph nodes , namely , histiocytic , fibroblastic , interdigitating , and follicular cells . their main function is the presentation of antigens and the generation and regulation of the germinal center reaction . follicular dendritic cells participate in the immune system by presenting antigens for b cells and by stimulating b cell proliferation and differentiation . these cells are localized to areas of b cells in the germinal centers of lymphoid follicles . interdigitating dendritic cells participate in the immune system by stimulating t lymphocytes and are found in the t cell areas of peripheral lymphoid tissues ( 1 - 3 ) . dendritic cell neoplasms are rare tumors , though they are being recognized with increasing frequency . they were previously classified as lymphomas , sarcomas , or histiocytic neoplasms . however , the world health organization ( who ) classified dendritic cell neoplasms into five groups : langerhans cell histiocytosis ( lch ) , langerhans cell sarcoma ( lcs ) , interdigitating dendritic cell sarcoma / tumor ( idcs ) , follicular dendritic cell sarcoma / tumor ( fdcs ) , and dendritic cell sarcoma , not specified otherwise ( 4 ) . idcs are infrequent neoplasms , and therefore , a limited number of cases have been reported . although most arise in lymph nodes , rare cases of idcs have been described in extranodal sites , such as the spleen , small intestine , nasopharynx , skin , testis , ovary , urinary bladder , and tonsils ( 5 - 12 ) . here , we report a case of extranodal idcs presenting in the pleura , a hitherto unreported site . on october 1st , 2009 , a 32-yr - old man visited the outpatient clinic with a 1-month history of progressively worsening blood - tinged sputum and chest pain . the patient had worked in a small educational institute for three years , and was currently working as a company employee . however , he denied exposure to asbestos . on physical examination , hepatosplenomegaly and peripheral lymphadenopathy were absent , but a chest examination revealed retraction and tenderness of the left chest wall . laboratory testing revealed hemoglobin 12.3 mg / dl , white cell count 11,100/l , and platelet count 519 10/l . computed tomography ( ct ) of the chest showed irregular pleural thickening and pleural effusion in the left lung ( fig . an incisional biopsy of pleura was performed , and histologic findings suggested a malignant undifferentiated tumor . the tumor cells had oval to spindled nuclei , and indented nuclei were frequently observed . the cytoplasm of the tumor cells was abundant and slightly eosinophilic with an indistinct border ( fig . , immunohistochemistry was performed on the benchmark automated immunostaining system ( ventana medical system , tuscon , az , usa ) . the monoclonal antibodies used were the following : s100 ( 1:800 ; dako , glostrup , demark ) , vimentin ( 1:200 ; dako ) , cd45 ( 1:100 ; leica , newcastle - upon - tyne , uk ) , ck ( 1:600 ; leica ) , myeloperoxidase ( 1:200 ; leica ) , hmb45 ( 1:150 ; leica ) , cd1a ( 1:20 ; leica ) , cd20 ( 1:200 ; leica ) , cd21 ( 1:60 ; leica ) , cd23 ( 1:100 ; leica ) , cd31 ( 1:300 ; leica ) , cd34 ( 1:20 ; leica ) , cd56 ( 1:150 ; leica ) , ck5 ( 1:300 ; leica ) , wt-1 ( 1:40 ; leica ) , calretrenin ( 1:100 ; leica ) , cd68 ( 1:600 ; dinona , iksan , korea ) , cd3 ( 1:300 ; neo , fremont , usa ) , cd35 ( 1:50 ; cell marque , rocklin , ca , usa ) , and ck6 ( 1:50 ; thermo , fremont , ca , usa ) . 3 ) , vimentin , and cd68 , but negative for cytokeratin ( epithelial cell marker ) , myeloperoxidase ( myeloid cell marker ) , hmb45 ( melanoma marker ) , cd1a ( lcs marker ) , cd3 ( t - cell marker ) , cd20 ( b - cell marker ) , cd21 , cd23 , cd35 ( fdcs marker ) , cd31 ( vascular endothelial cell marker ) , cd34 ( myeloid stem cell marker ) , cd56 ( neuroendocrine cell marker ) , ck5 , ck6 , wt-1 , and calretrenin ( mesothelioma marker ) . the patient underwent a positron emission tomography ( pet)-ct scan , which revealed 18-fluoro - deoxyglucose ( fdg ) uptake in the thickened pleura and whole axial skeleton ( standardized uptake value ( suv ) ; 10.5 and 9.8 ) compatible with malignant tissue ( fig . subsequently , the patient was treated with two courses of chop ( cyclophosphamide , doxorubicin , vincristine , prednisone ) and one course of imep ( ifosfamide , methotrexate , etoposide , prednisolone ) . however , the pleura - based masses were aggravated , and he died of progressive disease 3 months after diagnosis . tumors arising from dendritic cells , such as , fdcs and idcs , are very rare . fewer than two hundreds of cases have been reported to date ( 4 ) , and only 37 cases of idcs have been reported in the english literature ( 5 ) . idcs usually is encountered in a lymph node , but extranodal idcs is rare and can occur in a wide variety of sites ( 5 - 12 ) . the recognition of extranodal idcs requires a high index of suspicion because of its rarity . we present a case of extranodal idcs in the pleura that was diagnosed using a combination of morphologic and immunophenotypic characterizations . as far as we know , only one case of idcs with pleural effusion has been reported , in which malignant pleural effusion occurred during disease course in a idcs patient presented with multiple lymphadenopathies ( 13 ) . moreover , the reported case might not be idcs due to its expression of surface cd1a in the tumor cells . to the best of our knowledge , this is the first case report to describe extranodal idcs initially presented with diffuse pleural involvement . the diagnosis was confirmed histologically on slides stained with hematoxylin and eosin and a wide panel of antibodies , which included probes recognizing antigens specifically expressed by follicular and interdigitating dendritic cells ( 2 , 3 ) . neoplastic cells were large , fusiform spindle cells with indistinct cell borders , oval central nuclei , finely dispersed chromatin , and small but prominent nucleoli , and often formed a storiform or whorled , fascicular growth pattern . idcs should be differentiated from fdcs , lcs , s100 positive histiocytic tumors , melanoma , and fibroblastic reticular cell tumors . immunohistochemistry demonstrated neoplastic cells positivity for all histiocytic markers , including cd68 , lysozyme , and macrophage transcription factor pu.1 , and showed that the dendritic cell markers fascin and s100 were strongly expressed . however , they were negative for cd1a ( lcs marker ) , cd21/23/35 ( fdcs marker ) , cd20 ( b cell marker ) , cd3 ( t cell marker ) , and cd34 ( myeloid stem cell marker ) ( 5 - 8 ) . neoplastic cells in our case were strongly positive for s100 and negative for t cell , b cell , epithelial , and follicular dendritic cell markers . treatments administered have varied in accord with clinical context of the affected patients . in patients with localized disease several chemotherapeutic regimens have been tried including chop , abvd ( doxorubicin , bleomycin , vinblastine , dacarbazine ) , dhap ( dexamethasone , cisplatin , high - dose cytarabine ) , epoch ( etoposide , prednisone , vincristine , cyclophosphamide , doxorubicin ) , ice ( ifosfamide , carboplatin , etoposide ) , and cisplatin / epirubicin with limited response ( 1 , 3 , 6 ) . for the greater part , remission durations are usually short , and limited results for bone marrow transplantation are not encouraging ( 3 ) . our patient was treated using the chop and imep regimens , but eventually succumbed to disease progression . furthermore , its unusual location , extreme rarity , and the morphological similarities between idcs and fdcs and with other poorly differentiated tumors can easily delay diagnosis . the possibility of idcs with an unusual extranodal site should be considered when an undifferentiated neoplasm with a mixed population of lymphocytes is encountered . awareness of this tumor , particularly in extranodal sites , and the use of immunohistochemical stains with appropriate markers are crucial for arriving at a correct diagnosis .

interdigitating dendritic cell sarcoma ( idcs ) is an extremely rare neoplasm arising from the antigen - presenting cells of the immune system . this disease usually involves the lymph nodes , and rarely , extranodal sites may be affected . the authors report a case of extranodal idcs presenting in the pleura . a 32-yr - old man presented with progressive chest pain . imaging studies showed diffuse pleural thickening with pleural effusion . morphological and immunohistochemical analysis of an incisional biopsy of the pleura were consistent with a diagnosis of idcs ; tumor cells were positive for s100 and cd45 , but negative for cd1a , cd21 , cd35 , b cell and t cell markers . the patient was administered chemotherapy , but died of progressive disease . although its incidence is extremely rare , this case suggests that extranodal idcs should be considered in the differential diagnosis of undifferentiated neoplasms and that immunohistochemical staining be performed using appropriate markers .

permanent tooth crown fracture is one of the common traumatic problems among different age groups and both genders . several techniques have been proposed for restoring fractured crowns , including stainless steel crowns , orthodontic bonds , pin retained resin restorations , basket crowns , composite resins with acid etch adhesives techniques , porcelain veneers and jacket crowns , each of which show diverse degrees of success . however , the development of composite resins has entailed the use of adhesive materials and techniques , which may also be applied for restoration and reattachment of fractured teeth . moreover , esthetic dimensions of restored teeth , which may be achieved by means of a crown , decrease the traumatic impact on patients with injured teeth . fragment bonding has several advantages over other techniques which include : a ) superior natural appearance as no composite resin appears as natural and translucent as the patient 's own incisor enamel ; b ) harmonious wear , as most composite restorations wear out faster than the enamel while the patient 's own incisor edge wears harmoniously ; c ) preservation of the pulp vitality ; and finally , d ) economical and less time consuming reconstruction of the contour and morphology of the crown.[368 ] some researchers explain how to technically reattach the fractured part or how to improve the bond strength.[23914 ] keeping the fractured part in a wet environment before reattaching has been studied by others , supporting the effect of a moist environment . since successful reattachment of a fractured fragment depends on the time of restoring the fractured part after trauma ( which may vary from a few hours to a few days ) and the patient 's awareness , the fractured part may variably lose its moisture . the restoration time can affect bond strength of these restorations because dentin moisture is essential for achieving high bond strength of composite resins with dentin . no studies have yet been reported on the kinds of environments , for example , saliva , water , milk or normal saline , in which parents may store fractured parts of teeth , like what should be done in case of dealing with avulsed teeth , before referring to the dentist . we may also come across avulsed teeth with fractured parts that are carried to the clinic in different storage environments . the focus of this study was to examine the effect of different storage environments on the quality of fragment restoration and the bond strength of restored teeth through reattachment methods . in this experimental laboratory study , 60 human mandibular incisors , which were extracted because of periodontal diseases , without any defects such as fractures , decalcification , or caries were collected . the teeth were randomly and equally divided into five groups of 12 each . after scaling the teeth crowns , they were prepared for fracturing . a line was traced on each tooth , 3 mm from the incisal edge and parallel to it . 918f , d + z , diamant , lemgo , germany ) , an enamel - deep fracture line was made on the lingual side of each tooth ( situated on the traced line ) . on the labial side of the line , a small notch was made in the middle of the surface to prevent the blade used later on from slipping . the force was applied on the enamel cut by a blade on the lingual surface of the tooth and by another blade positioned in the opposite direction on the labial surface . 21 , aesculap ag , tuttlingen , germany ) were replaced for every three samples . the teeth displaying a fracture pattern different from the premeditated line or an unclear fracture line were discarded at this stage . then , the apical parts were kept in distilled water and at an ambient temperature . for the purposes of this study , five storage environments including normal saline , water , common cow 's milk ( pegah milk , isfahan , iran ) , saliva ( artificial saliva ; bioxtra , biohealth care , belgium ) and a dry environment were prepared in which the fractured parts of the teeth were to be preserved for 24 hours . storage environments for the teeth fragments according to their groups in the first group , the fractured parts were rinsed , dried and bonded to the remaining part using a bonding agent ( single bond , 3me spe , st . both the fractured surfaces were etched by phosphoric acid 35% ( ultra etch , ultradent products , inc . , south jordan , ut , usa ) for 15 seconds ; they were rinsed with water for 15 seconds and dried with paper towel in a way that slight moisture remained on the surfaces to be attached . two layers of single bond were applied on the etched surfaces in such a way that first , one layer of the bonding agent was used and after 10 seconds , when priming was done , it was thinned gently by air blow for 3 seconds . then , the second layer was immediately placed and thinned for 3 seconds to get a shiny and glossy surface . following the manufacturer 's instruction , the bonding agent was cured using a light curing unit ( coltolux 75 , coltene / whaledent inc . , mahwah , nj , usa ) at a wavelength of 480 nm . for reattaching the fractured part to the tooth , a flowable composite ( filtek flow , 3 m espe , st . paul , mn , usa ) was used on both the fractured surfaces , and the two parts of each tooth were pressed together and cured for 40 seconds from the labial and lingual directions and for 30 seconds from the mesial and distal sides . any excessive composite resin was removed with a sharp scalpel blade and the reattached samples were kept in normal saline in an incubator at 37c . similar procedures were repeated for groups 2 , 3 , 4 and 5 ; however , the fractured parts were stored in water , milk , saliva and dry environments , respectively . in the next step , each sample was mounted in an acrylic block ( acropars , marlic co. , tehran , iran ) . the teeth roots were embedded in acrylic resin up to the cingulum , so that the line axis of the tooth was parallel with the line axis of the acrylic block and the incisal edge was parallel with the horizontal line . the specimens were loaded on a universal testing machine ( dartec hc 10 , dartec ltd . , the load was applied using a ball - shaped stainless steel device , measuring 3 mm in diameter . the force application tip was positioned exactly on the fractured line , at 90 on the facial surface of the crowns and the machine was activated at a speed of 0.5 mm / min until the specimens fractured . the results were compared using one - way analysis of variance ( anova ) and tukey 's statistical tests at a 95% level of significance ( < 0.05 ) . after the samples were fractured , they were recollected in order to study the fracture mode in each group . the specimens were loaded on a universal testing machine ( dartec hc 10 , dartec ltd . , stourbridge , england ) . the load was applied using a ball - shaped stainless steel device , measuring 3 mm in diameter . the force application tip was positioned exactly on the fractured line , at 90 on the facial surface of the crowns and the machine was activated at a speed of 0.5 mm / min until the specimens fractured . the results were compared using one - way analysis of variance ( anova ) and tukey 's statistical tests at a 95% level of significance ( < 0.05 ) . after the samples were fractured , they were recollected in order to study the fracture mode in each group . one - way anova indicated differences in the amount of force required for making fractures in different groups ( p < 0.001 ) . there was no statistically significant difference between groups 3 and 4 , but values for these groups were larger than those of the other groups [ table 3 ] . the required force for fracture was lesser in groups 1 and 2 , compared with groups 3 and 4 . group 5 had the lowest required force for fracture , though not significantly different from groups 1 and 2 ( p > 0.05 ) . required force ( n ) to fracture specimens according to the storage environment for each experimental group level of significance according to tukey 's test the fracture pattern in restoration with reattachment in all groups revealed adhesive fractures in the reattachment line . mandibular incisors are suitable for studying the required force for fracture , have little difference and variation in their dimensions , and are easily available . in this study , other retentive methods such as enamel bevel , chamfer preparation or retentive dental grooves were not used , in order to only investigate the effect of the storage environment on fractured strengths . also , single bond was used in order to have a durable and strong enamel bond along with an acceptable dentin bond , and not the self - etching systems which have a weaker enamel bond . in a study , toshihiro et al . observed that reattachment of the fractured part resulted in discoloration because of losing its moisture ; but after 1 month , the fragment had regained some of the original color and translucency , and after 1 year , the reattached fragment had satisfactory esthetics and excellent function . however , in the present study , focus had been on achieving better bond strengths and the fractured parts had to be kept in proper storage environments . some studies recommend keeping fractured parts in moisture in order to prevent dehydration or discoloration . some suggest a normal saline solution at 37c and others recommend water or salt solution in a closed container . milk , normal saline , saliva , and water were selected for this study because they are easily available . the first choice for moist environment is milk and saliva , and the second choice is solutions which are hypertonic . moreover , when the tooth is avulsed , parents are advised to store it in milk or saliva . therefore , in case of other tooth injuries such as a crown fracture , some parents tend to keep the fragment in milk or saliva rather than water . as there was no study related to storage environments of fractured parts , and different storage environments are suggested , this study was conducted to examine the best storage environment before reattachment . the required force for fracturing the healthy teeth is twice as much as that needed for the reattached samples . since the average force imposed on the anterior teeth is about 150 n and the force needed to break the reattached parts is higher than that , the reattachment of the fractured part can be durable . it was noted that the fractured part which was kept in a dry environment before reattachment had the lowest bond strength , supporting farik 's finding . intact sound dentin which is stored in a dry environment for 24 hours retains only about 25% of the total amount of its moisture . it seems that this partial loss of dentin moisture and its shrinkage results in the reduction of the composite surface contact with dentin . besides , over acid - etching due to loss of moisture in the fractured part 's dentin may occur and result in unfavorable effects on the bonding condition . the bond strength of dry group in our study was not significantly different from that of the water or normal saline groups . due to the difference in the storage environments ( milk or saliva in this study ) and the role of rinsing and rinsing was also done in the negative control group ; this may be the reason why the control group produced results similar to those of the groups with normal saline and water storage environments . according to farik , moisturizing the fractured part affects the bond strengths and the bond strength improves by increasing the moistening time . also , capp et al . found that a dried fragment has a lower bond strength compared to a fractured part which is kept in a moist environment or is moisturized before reattachment . in groups whose fractured parts were kept in normal saline or water , their bond strength increased more than those of the groups whose fractured parts were kept in a dry environment . the best storage environments , as observed in this study , are milk and saliva . it seems that in these two environments , little osmotic and dimensional changes happen in the dentin surface and a stronger bond strength is achieved . there is no mention of this in the current literature and more investigations are required on the subject . it has been proved that milk elements such as calcium and phosphate can harden and stiffen both demineralized and healthy dentin by permeating the surface . this is probably the reason why enhancement of bond strength was observed in the milk and saliva groups which were rich in calcium and phosphates . calcium and phosphate sedimentation can also affect the surface topography of dentin and the degree of its dissolution during acid etching , which may also explain the better bond strength in the milk and saliva groups . however , further sem ( scanning electron microscopy ) investigations of fractured surfaces before and after acid etching are suggested for evaluation of the surface roughness in different groups , and also for measuring their thickness and depth of the hybrid layer . this study shows that the force required to fracture the restored teeth is affected by the environment where the fractured part is kept before bonding .

aim : the aim of this study was to examine various storage environments for storing fragments before being bonded to the remaining teeth and also estimate the required force to fracture the restored teeth.materials and methods : sixty mandibular incisor teeth were fractured on the incisal one - third and were divided into five groups of 12 each to be stored in normal saline , water , milk , saliva and dry environments for 24 hours . all the fractured parts in each group were bonded to their relevant apical parts by an etch and rinse bonding system and a flowable composite resin . the fracture resistance was measured by a universal testing machine , and the results were analyzed using one - way anova and tukey statistical tests.results:the results revealed that the difference among the five groups was statistically significant ( p<0.001 ) . tukey tests showed that the force required for fracturing fragments kept in the milk and saliva environments were significantly higher than those for the normal saline , water and dry environments ( p<0.05 ) .conclusions : it was concluded that keeping the fractured parts in milk and saliva environments can increase the required force for fracturing teeth more than the other environments .

december 2013 , from 125 hospitals throughout the country , we collected 301 serum samples from hospitalized persons who had sfts signs and symptoms , such as high fever ( temperatures > 38c ) , vomiting , diarrhea , and/or fatigue and showed laboratory parameters consistent with thrombocytopenia and/or leukocytopenia . we conducted reverse transcription pcr ( rt - pcr ) to detect the sftsv medium ( m ) segment gene from acute - phase serum specimens with a previously described method ( 6 ) . we also detected the sftsv small ( s ) segment gene by rt - pcr with specific primers ( sf3 , 5-gggtccctgaaggagttgtaaa-3 ; sr1 , 5-tggtgagcagcagctcaatt-3 ) . the rt - pcr conditions were as follows : an initial step of 30 min at 50c for reverse transcription and 15 min at 95c for denaturation , followed by 35 cycles of 20 s at 95c , 40 s at 58c ( for m segment ) or 55c ( for s segment ) , and 30 s at 72c and a final extension step of 5 min at 72c . from the 301 samples , we detected m and s segment genes from 34 and 29 samples , respectively . the nucleotide sequences were assembled by the seqman program implemented in dnastar software ( version 5.06 ; madison , wi , usa ) to determine the consensus sequences . the nucleotide sequences of the korea isolates showed 93%98% homology to the china and japan isolates . to isolate sftsv , we inoculated subconfluent monolayers of vero e6 cells with the rt - pcr positive serum . after the monolayers underwent 3 blind passages in new monolayers of vero e6 cells ( 8) , we examined the vero e6 cells for sftsv by rt - pcr . we considered the virus to be isolated when the specific genes were amplified by rt - pcr . isolation of sftsv also was confirmed by indirect immunofluorescent assay ( ifa ) ( figure 1 , panels a , b ) and electron microscopy ( figure 1 , panel c ) . for ifa , cells were harvested , inoculated , and fixed with acetone on teflon - coated well slides . ifa was conducted by using a monoclonal sftsv nucleocapsid protein ( n ) antibody ( manufactured in our laboratory ) as the primary antibody . n proteins of sftsv were distributed throughout the cytoplasm ( figure 1 , panels a , b ) . by electron microscopy , vero e6 cells infected with the sftsv korea isolate kajjh showed bunyavirus - like particles , 80100 nm in diameter , located in cytoplasmic vacuoles , presumably in the golgi apparatus ( figure 1 , panel c ) . isolation of severe fever with thrombocytopenia syndrome virus ( sftsv ) from case - patients , south korea , 2013 . a , b ) indirect immunofluorescent features of vero e6 cells primed with sftsv n protein monoclonal antibody and reacted with fluoresce in isothiocyanateconjugated anti - mouse igg . the amplified dna products from the isolates were sequenced and compared with the sequences of other genbank - registered sftsv isolates . the sequences of partial m and s segments of the 26 korea isolates ( genbank accession nos . kf282701 , kf282702 , and kj739543kj739592 ) were closely related to those of the sftsv isolates from china and japan with 92%100% identity . a phylogenetic tree was constructed by the neighbor - joining method on the basis of the partial m ( figure 2 , panel a ) and s segment ( figure 2 , panel b ) sequences of the korea sftsvs in the study and 15 sftsvs from china and japan registered in genbank . sftsv isolates formed 2 major clusters in m and s segment sequences , and 1 other small group comprising only korea isolates , kagnh2 and kaush , was formed in m - segment sequences . some korea isolates clustered with the major group of china isolates , forming the second group . a and b ) phylogenetic analysis of sftsv korea isolates based on the partial medium ( m ) and small ( s ) segment sequences . the phylogenetic trees were generated by mega version 5.2 software ( http://www.megasoftware.net/ ) from aligned nucleotide sequences of 16 isolates of phleboviruses , including the identified sftsv . m and s partial nucleotide sequences of sftsv korea isolates were compared with homologous sequences of previously characterized sftsvs . sequences were analyzed by the neighbor - joining method based on the maximum composite likelihood model . the minimal length trees shown were supported as the majority rule consensus trees in 5,000 replicates . we also isolated several sftsvs from case - patient serum and analyzed the phylogenetic properties of the isolates . the first sfts case was identified in a retrospective study from 2012 ( 3 ) . another group diagnosed the first of the 35 cases in the country ; we diagnosed the other 34 cases , from which we isolated the 26 sftsvs . the major signs and symptoms of the 35 case - patients , including fever ( 100% ) , gastrointestinal symptoms ( 74% ) , fatigue ( 74% ) , thrombocytopenia ( 100% ) , and leukocytopenia ( 100% ) , were similar to those of case - patients in china and japan ( 9 ) . the case fatality rate for sfts in south korea was 47.2% ( 17/36 ) , higher than that of the recent china cases ( 8.7% ) ( 10 ) . the low sensitivity of the detection method , the conventional 1-step rt - pcr , and the absence of a serologic diagnosis may have contributed to the relatively high case fatality rate . most cases occurred in older persons ; 80% of patientswere > 50 years of age . in many case - patients , the disease evolved during a relatively warm time of year , from late spring to early autumn ( figure 3 , panel a ) . the geographic distribution of sfts case - patients also indicated that environmental temperature affected the sfts prevalence because many ( 86% , 30/35 ) sfts cases evolved in relatively warm southern provinces and cities south of chungcheongbuk , chungcheongnam , and gangwon provinces ( figure 3 , panel b ) . we have also observed that the tick density is high during may august , a generally warm season in south korea ( 7 ) . these results indicate that the virus infection in humans is closely related to a high tick density and sftsv infection in ticks in a warm climate . seasonal ( a ) and geographic ( b ) distribution of casepatients with severe fever with thrombocytopenia syndrome ( sfts ) , south korea , 2013 . a ) white and black bars indicate the numbers of total and deceased sfts patients , respectively , in the indicated months . b ) black circles indicate the approximate residential regions of 35 sfts case - patients in 2013 in south korea . gg , gyeonggi province ; gw , gangwon province ; cb , chungcheongbuk province ; cn , chungcheongnam province ; gb , gyeongsangbuk province ; gn , gyeongsangnam province ; jb , jeollabuk province ; jn , jeollanam province ; jj , jeju special autonomous province . as described in another report , japan isolates formed an independent cluster from the china isolates ( 2 ) . in our current study , sftsv isolates formed 2 major clusters . most of the korea isolates formed a cluster with the japan isolates , although some korea and china isolates were included in the other group , perhaps not surprising given the geographic location of south korea between china and japan .

during 2013 , severe fever with thrombocytopenia syndrome was diagnosed in 35 persons in south korea . environmental temperature probably affected the monthly and regional distribution of case - patients within the country . phylogenetic analysis indicated that the isolates from korea were closely related to isolates from china and japan .

although anatomical liver resection is the standard of care for treatment of neoplastic hepatic disease ( either primary or secondary ) , non - anatomical liver resections can still be useful in some situations . it is a low - morbidity technique that can be timely used for tumors near the hepatic surface . it also has become a useful tool after widespread implementation of neoadjuvant chemotherapy for hepatic metastasis , which many times reduces lesions dimensions to small non - anatomical hepatectomy offers the advantage of preserving hepatic parenchyma when compared with segment - oriented hepatectomy , being a safe option with good oncological results in patients with chronic hepatic disease and hepatocellular carcinoma and in the setting of staged hepatectomy in patients with multiple nodules [ 35 ] . despite being at first impression a very easy technique , one may face some difficulties while performing an enucleation of a tumor that is not visible at the hepatic surface . after proper localization of a small lesion with intraoperative ultrasonography and initiation of the transection of the parenchyma , the resulting bleeding and disruption of the hepatic tissue can easily make the tumor no longer visually identifiable if not recovered in the initial resected specimen , and further ultrasonography examination may not access the tumor after disruption of the hepatic tissue . this article describes a simple , efficient and low - cost maneuver to make enucleation of hepatic lesions not visible at the hepatic surface a precise and straight to the point technique . it consists of inserting methylene blue on the lesions by ultrasonographic guidance . based on preoperative image studies , the portion on the liver that contains the tumor is fully mobilized by transection of hepatic ligaments . then , intraoperative ultrasonography is performed in order to achieve precise localization of the lesion and estimation of its deepness ( fig . 1 ) . figure 1:hypoechoic 5-mm lesion at 2 cm depth ( metachronous metastatic tumor from colorectal carcinoma ) ( arrow ) . hypoechoic 5-mm lesion at 2 cm depth ( metachronous metastatic tumor from colorectal carcinoma ) ( arrow ) . under ultrasonography guidance , at this time , 5 ml of methylene blue is inserted , and the needle is retracted from the liver . the first result is that a small area around the tumor and the lesion itself will immediately change its echographic characteristics , becoming much more hyper - reflective and easily identifiable by ultrasonography ( fig . figure 2:(a ) methylene blue injection under ultrasonographic guidance and ( b ) easily identifiable methylene blue - injected lesion with hyper - echoic pattern ( arrow ) . ( a ) methylene blue injection under ultrasonographic guidance and ( b ) easily identifiable methylene blue - injected lesion with hyper - echoic pattern ( arrow ) . after that , glisson 's capsule is marked with cautery leaving a 2-cm margin . usually , transection is performed with bipolar forceps . during the transection , close to the depth previously defined , intraoperative ultrasonography is repeated , and a well - defined area containing the tumor and methylene blue will be identifiable , despite the disruption of the hepatic parenchyma ( fig . 3 ) . resection is completed and specimen checked to confirm the presence of the lesion inside . figure 3:after parenchymal disruption , hyper - echoic lesion still clearly by ultrasonography ( arrow ) . after parenchymal disruption , hyper - echoic lesion still clearly by ultrasonography ( arrow ) . if the tumor is not retrieved with the specimen , despite the bleeding caused by parenchymal transection , further inspection of the manipulated hepatic bed will disclose the presence of methylene blue , and under direct visualization of the area of the tumor , a second specimen is retrieved containing the lesion ( fig . 4 ) . figure 4:(a ) methylene blue - injected area containing the tumor within the parenchyma and ( b ) two specimens : the smaller one , that was displaced deeper within the parenchyma , containing the tumor . ( a ) methylene blue - injected area containing the tumor within the parenchyma and ( b ) two specimens : the smaller one , that was displaced deeper within the parenchyma , containing the tumor . based on preoperative image studies , the portion on the liver that contains the tumor is fully mobilized by transection of hepatic ligaments . then , intraoperative ultrasonography is performed in order to achieve precise localization of the lesion and estimation of its deepness ( fig . 1 ) . figure 1:hypoechoic 5-mm lesion at 2 cm depth ( metachronous metastatic tumor from colorectal carcinoma ) ( arrow ) . hypoechoic 5-mm lesion at 2 cm depth ( metachronous metastatic tumor from colorectal carcinoma ) ( arrow ) . under ultrasonography guidance , at this time , 5 ml of methylene blue is inserted , and the needle is retracted from the liver . the first result is that a small area around the tumor and the lesion itself will immediately change its echographic characteristics , becoming much more hyper - reflective and easily identifiable by ultrasonography ( fig . 2b ) . figure 2:(a ) methylene blue injection under ultrasonographic guidance and ( b ) easily identifiable methylene blue - injected lesion with hyper - echoic pattern ( arrow ) . ( a ) methylene blue injection under ultrasonographic guidance and ( b ) easily identifiable methylene blue - injected lesion with hyper - echoic pattern ( arrow ) . usually , transection is performed with bipolar forceps . during the transection , close to the depth previously defined , intraoperative ultrasonography is repeated , and a well - defined area containing the tumor and methylene blue will be identifiable , despite the disruption of the hepatic parenchyma ( fig . 3 ) . resection is completed and specimen checked to confirm the presence of the lesion inside . figure 3:after parenchymal disruption , hyper - echoic lesion still clearly by ultrasonography ( arrow ) . after parenchymal disruption , hyper - echoic lesion still clearly by ultrasonography ( arrow ) . if the tumor is not retrieved with the specimen , despite the bleeding caused by parenchymal transection , further inspection of the manipulated hepatic bed will disclose the presence of methylene blue , and under direct visualization of the area of the tumor , a second specimen is retrieved containing the lesion ( fig . 4 ) . figure 4:(a ) methylene blue - injected area containing the tumor within the parenchyma and ( b ) two specimens : the smaller one , that was displaced deeper within the parenchyma , containing the tumor . ( a ) methylene blue - injected area containing the tumor within the parenchyma and ( b ) two specimens : the smaller one , that was displaced deeper within the parenchyma , containing the tumor . it was first prepared by german chemist heinrich caro in 1876 and is on the world health organization 's list of essential medicines as one of the most important medication needed in a basic health system [ 6 , 7 ] . it is described as the first fully synthetic drug used in medicine being used in the treatment of malaria since 1891 and is largely used in many clinical situations with safety . . however , non - anatomical wedge resections can be effective and have good oncological results especially in small metastatic lesions and has the advantage of sparing hepatic parenchyma , that is indispensable in patients with chronic hepatic disease or with severe chemotherapy - associated liver injury and in the setting of staged hepatectomies or in patients with multiple lesions [ 1 , 9 ] . during the enucleation of a hepatic tumor not visible in the hepatic surface , after parenchymal transection , disruption of the hepatic tissue many times makes the tumor not visible any longer by repeat ultrasonography , which is often performed to check the depth of the transection . furthermore , if the specimen is retracted and the tumor is not present , the bleeding in the cutting line makes it difficult to find the tumor within the hepatic parenchyma . injecting methylene blue in the tumor overcomes both difficulties cited above . the lesion becomes much more hyper - echogenic at ultrasonography even after the parenchymal transection , and the tumor injected with methylene blue presents a great deal more visual contrast with the surrounding hepatic tissue , becoming easily identifiable if a first specimen was retracted not containing the lesion . this simple maneuver can make enucleation of hepatic tumors not visible at the hepatic surface an easier , faster and more precise maneuver . it presents the advantages of making the area of the tumor much more hyper - reflective at intraoperative ultrasonography even after hepatic transection and much more visually identifiable within the hepatic parenchyma after an initial specimen is retracted not containing the tumor and further resection is needed .

enucleation of hepatic tumors is a low - morbidity technique with adequate oncological results that is useful in many clinical settings . compared with anatomical liver resections , it offers the advantage of maximal hepatic parenchymal preservation . however , some technical adversities may occur during the enucleation of liver tumors , such as difficulty in finding the lesions by intraoperative ultrasonography after hepatic transection or further visually spotting the tumor within the parenchyma if a first specimen is retracted not containing the lesion . we describe an innovative technique that overcomes these possible adversities and makes the enucleation of liver tumors easier and more precise .

an extensive involvement of mesenteric fat tissue of the small bowel with chronic non - specific inflammatory disease , first reported by jura et al . in 1924 was described , detailed , and named as mesenteric panniculitis ( mp ) by ogden et al . in 1960 . mp is always discussed with pathological findings concerning its etiology and 3 components of histology , fibrosis , chronic inflammation , and fat necrosis , suggesting various mechanisms of disease ( called sclerotic mesenteritis , mesenteric panniculitis , and mesenteric lipodystrophy , respectively ) . histologically , mp lesion is characterized by the infiltration of mesenteric fat tissue by inflammatory cells , mainly consisting of lymphocytes and plasmacytes , along with a mixture of fat necrosis and fibrosis . although the diagnosis of mp before biopsy is primarily based on guesswork , computed tomography ( ct ) findings are helpful for cases in which mesentery biopsy is problematic . the clinical course of mp is usually benign , and spontaneous remission is quite common without specific treatment . the pathogenesis of mp remains obscure and many associated diseases are known , including mechanical stimulation such as surgery or trauma , infections , vascular diseases , and malignant and non - malignant neoplasms . the occurrence rate of lymphoma as an underlying disease is 15% or more , and no malignant involvement of the mesentery was diagnosed in almost all cases . in a case ( 8 cases ) suggested that mesenteritis was a non - specific response to underlying lymphoma . ogden ( 2 cases ) and perez - ferriols ( 1 case ) both reported on the association of these 2 diseases . a 55-year old woman presented with right cervical lymph node swelling in july , 2004 , followed by inguinal lymph node swelling a few weeks later . the results of the blood and bone marrow examinations performed at that time are shown in table 1 . a lymph node biopsy of the inguinal area revealed grade 2 follicular lymphoma . ct images of her neck , thorax and abdomen , and fdg - pet revealed stage iv disease . she was diagnosed as having stage iv lymphoma with femoral bone involvement , as confirmed by femoral mri . her follicular lymphoma international prognostic index ( flipi ) was intermediate ( stage and lymph - node lesions ) . igh - bcl rearrangement ( fish ) was detected in her lymph nodes and bone marrow cells , although neither morphological abnormality nor apparent involvement of lymphoma cells were revealed . b symptoms were absent ; however , since she complained of bone pain and it was progressive , we decided to treat her with chemotherapy . r - chop chemotherapy consisted of rituximab ( 375 mg / m , day 0 ) , cyclophosphamide ( 750 mg / m , day 1 ) , doxorubicin ( 50 mg / m , day 1 ) , vincristine ( 1.4 mg / m , day 1 ) , and prednisolone ( 100 mg / kg body weight , day 15 ) , injected tri - weekly until 6 courses were completed . at this point only a partial response ( pr ) was observed through objective radiological evaluations ( for nodal masses fdg - pet was negative and more than 50% regression was observed on ct ) . after r - chop , 2 courses at a 3-week interval of the aces regimen ( cytarabine 2,000 mg / m day 5 , carboplatin 100 mg / m day 14 , etoposide 80 mg / m days 14 , methylprednisolone 500 mg / body days 15 ) were used as salvage chemotherapy , after which her disease was considered to be in cr ( igh - bcl rearrangement in her lymph nodes and bone marrow became negative ) . at the same time , a contrast - enhanced peritoneal mass appeared on ct imaging ( figure 1a ) and fdg - pet ( figure 1b ) . we identified the pathological etiology of the peritoneal lesion proceeding to the peripheral blood stem cell transplantation ( pbsct ) by ct - guided biopsy , which revealed mesenteric panniculitis ( mp ) not concomitant with the lymphoma lesion ( figure 1c ) . however , the bone lesion recurred in june , 2005 , when she received pbsct . she has maintained cr with no progression of the mp mass for more than three years . cytogram of bone marrow revealed no obvious morphological changes and the involvement of lymphoma cells was not detected.component of blood cell white blood cells9100 /l ( 35009100 ) granulocytes69% ( 3279 ) eosinophils1% ( 06 ) basaophils2% ( 02 ) monocytes3% ( 08 ) lymphocytes25% ( 1859 ) red blood cells41510/l ( 376500 ) hemoglobin12.6 g / dl 11.315.2 ) hematocrit37.4% ( 33.444.9 ) platelets23.110/l(13.036.9)biochemistry total protein7.7 g / dl ( 6.78.3 ) albumin4.6 g / dl ( 4.05.0 ) total billirubin0.4 mg / dl ( 0.31.2 ) glutamic pyruvic transaminase19 iu / l ( 540 ) lactate dehydrogenase195 iu / l ( 115245 ) alkaline phosphatase259 iu / l ( 115359 ) blood urea nitrogen15.9 mg / dl ( 8.022.0 ) creatinine0.6 mg / dl ( 0.470.79 ) urine acid3.8 mg / dl ( 2.57.0 ) natrium142 meq / l ( 136147 ) potassium4.1 meq / l ( 3.65.0 ) chloride106 meq / l ( 98109)coagulation prothrombin time97% ( 70130 ) activated partial thromboplastin time28.5 sec ( 24.336.0 ) international normalized ratio1.02 ( 0.851.15 ) fibrinogen274 mg / dl ( 150400)bone marrow number of nuclear cells9.4 10/l ( 1020 ) megakaryocytes43.810/l ( 50150 ) myeloid / erythroid ratio2.36 ( 24 ) blasts0.2% ( 1.01.5 ) promyelocytes0.6% ( 2.06.5 ) figure 1imaging and pathologic evaluation of mesenteric panniculitis . during treatment and before sct , we evaluated the clinical course of the mesenteric mass by ct ( a ) and 18f - fdg - pet ( b ) . mesenteric hypertrophy before treatment reduced during chemotherapy ( i ) , after salvage chemotherapy ( ii ) , and before pbsct ( iii ) . an accumulation positioned at the mesenterium detected by fdg - pet ( i ) was more intensified after salvage chemotherapy ( ii ) and did not improve before pbsct ( iii ) . fatty necrosis surrounded by foamy macrophages and reactive lymph adenopathy was characteristic of the mesenterium . immunohistological staining failed to detect cd20 , cd10 , cd79a , and bcl-2 , with no indications of malignant lymphoma : ( i ) h - e stain ( 400 ) , ( ii ) h - e stain ( 1000 ) . imaging and pathologic evaluation of mesenteric panniculitis . during treatment and before sct , we evaluated the clinical course of the mesenteric mass by ct ( a ) and 18f - fdg - pet ( b ) . mesenteric hypertrophy before treatment reduced during chemotherapy ( i ) , after salvage chemotherapy ( ii ) , and before pbsct ( iii ) . an accumulation positioned at the mesenterium detected by fdg - pet ( i ) was more intensified after salvage chemotherapy ( ii ) and did not improve before pbsct ( iii ) . fatty necrosis surrounded by foamy macrophages and reactive lymph adenopathy was characteristic of the mesenterium . immunohistological staining failed to detect cd20 , cd10 , cd79a , and bcl-2 , with no indications of malignant lymphoma : ( i ) h - e stain ( 400 ) , ( ii ) h - e stain ( 1000 ) . mesenteric panniculitis is a lipodystrophy characterized by non - specific inflammatory disease first reported by ogden et al . reviewed 84 cases of mp pathologically and documented that a mixed histology of 3 components ( fibrosis , chronic inflammation , and fat necrosis ) existed in the lesions , which could be classified according to the dominant pathological changes , i.e. mesenteric lipodystrophy ( ml ) type , mesenteric panniculitis ( mp ) type , and sclerosing mesenteritis ( sm ) type . however , not all cases can be definitively categorized in these 3 subtypes because the histologically dominant subtype is often too varied to define as ml , mp , or sm , respectively . due to this pathological variation and the various underlying diseases of mp , the etiology of this disease is thought to be a single pathology with various causes including immunological reactions , malignancies , infection , physical stimulation , or traumatic disorders . past retrospective analysis reported that , in general , mp occurs in patients in their 60s ( median age of occurrence ) , has slightly higher incidence in men , is accompanied by abdominal pain , and is often associated with malignant lymphoma . reported that 8 among 53 reviewed cases of mp with malignant lymphoma led to complications related to mp . they could find no pathological involvement of lymphoma in the panniculitis lesion in any case . in 3 of the 8 cases , mp existed with malignant lymphoma concomitantly . in 2 other patients , the lymphoma lesion was found two or three months later . another 3 patients were diagnosed as having malignant lymphoma occurring in a different area from the mp lesion . however , no panniculitis has been revealed in lymphoma lesions by biopsy , and no obvious association has been reported until now . in our case , the mesenteric lesion progressed and was detected by fdg - pet imaging during chemotherapy , which reduced to remission the lymphoma lesions ( lymph nodes and femoral bone head ) . if we had regarded the mesenteric mass in our patient as refractory lymphoma , we would have had to administer a salvage regimen . if the mesenteric mass had been benign , we could have continued the existing regimen . the mp lesion regressed after the planned treatments , with no recurrence for three years . therefore , we recognized that her mp was chemotherapy - related panniculitis , since panniculitis is thought to be brought about by physical or chemical stimulation . although fdg - pet was an effective and powerful tool for the staging , localization , and response assessment of malignant lymphoma , the differential diagnosis for lymphoma lesions with physiological accumulation or inflammatory change is sometimes difficult . though fdg - pet / ct fusion imaging is more efficient for diagnosis of the active lymphoma lesion , a pathological diagnosis via biopsy is essential for cases in which a false positive is suspected . reviewed 19 oncological patients with mp and reported that fdg - pet had high specificity ( 100% ) among 11 fdg - pet - negative subjects and 88% sensitivity ( 7 out of 8 subjects ) . we concluded that mesenteric lesions suspected of progressing or recurring with positive uptake with fdg - pet should be diagnosed pathologically even if asymptomatic .

mesenteric panniculitis ( mp ) is a rare disease occasionally complicated with lymphoma . a 55-year old female presented with mp accompanied by malignant lymphoma . this patient was first treated for follicular lymphoma and subsequently for panniculitis . after 6 courses of r - chop chemotherapy , the treatment response was partial . an additional course of salvage chemotherapy led to a complete response . since the mesenteric mass progressed simultaneously with the regression of other lymphoma lesions , we performed a biopsy of the mesenteric mass and pathologically confirmed an mp lesion without lymphoma . subsequent high - dose chemotherapy led to cr and the mp lesion remained stable . in the present case , mp progressed with chemotherapy . we concluded that mesenteric lesions suspected of progressing or recurring should be diagnosed pathologically even if asymptomatic .

epiretinal membranes ( erms ) are characterized by wrinkling of the macular surface from cell proliferation . most commonly erms are noted in adults above the age of 50 years in association with posterior vitreous detachment ( pvd ) , laser photocoagulation , or after retinal detachment repair . a majority of erm in adults is of the cellophane macular reflex type referring to the thin transparent variety.1 erm in children and young adults is uncommon , because a pvd is uncommon in very young subjects . ocular trauma , pars planitis , ocular toxocariasis , ocular toxoplasmosis , combined hamartoma of the retina and retinal pigment epithelium , and coats disease are leading causes of secondary erm in children . the prevalence of erm in subjects less than 20 years of age is around 1 in 20,000.1 a majority of erm in young subjects is of the thick white contractile variety having strong adherence to retinal vessels.2,3 myofibroblasts , myoblastic differentiation of retinal pigment epithelial cells and fibrous astrocytes , as well as new collagen formation are more common in erm of young subjects than in erm in older subjects.4 we report a young adult with erm that underwent spontaneous release in a peculiar way ( erm tearing centrally ) apparently following valsalva maneuver . this 32 year - old healthy man complained of visual loss in the right eye 14 months prior to presentation and he was referred for surgical peeling of an erm ( figures 15 ) by two retina experts . two months before presentation , he indulged in heavy weight - lifting and noted repeatedly severe eye pressure during the exercise . two months later , ophthalmic exam revealed 6/6 uncorrected visual acuity with findings of a residual rolled - over erm supranasal to the fovea ( figure 6 ) . past fundus photograph 1.5 years ago revealed a dense macular gliosis with prominent radial stress line ( best seen on infrared photography ) throughout the posterior pole and centered around the thickest part of the membrane nasal to the disc ( as noted by red - free photograph [ figure 2 ] ) . intravenous fluorescein angiography done at the same time revealed obliteration of foveal avascular zone with tortuous macular capillaries and stretched out papillomacular vessels . optical coherence tomography ( oct ) done 1 year ago ( figure 5 ) revealed a diffuse erm thin temporal to the fovea and very thick nasal to the fovea with marked thickening of the central fovea . oct upon presentation demonstrated central peeling of erm ( figure 7 ) accompanied by normalization of central foveal thickness ( figure 8) . erm rupture could be noted with one edge ruptured temporally and the nasal edge rolling over ( figure 9 ) . there was no pvd identified by oct or by slit lamp fundus biomicroscopy with a 90 diopter lens . erm in young subjects commonly causes both metamorphopsia and reduced visual acuity from reduced axoplasmic flow , abnormal hemodynamic microcirculation , light - filtering effect of erm , and photoreceptor distortion by tangential traction.57 clinically , the superior and inferior vessels are narrowed while the perimacular vessels are pulled toward the epicenter with inner retinal striae . erm in young people and children is rare and may be caused by congenital defects resulting from persistent adhesions of primary vitreous to the retina.7 the clinical and ultrastructural features of juvenile macular pucker reflect a more rapidly changing , contractile tissue4 compared with the usually more quiescent features in most cases involving older patients . however in adults , pvd can damage the internal limiting membrane , thereby permitting the migration of glial cells to the retinal surface.6,8 alternate proposed hypothesis in adults is that an incomplete pvd provides the conditions suitable for membrane proliferation in the adhesion area between the vitreous and the retina . the cells involved in this process are retinal pigment epithelium metaplastic cells , glial cells ( muller cells and astrocytes ) , hyalocytes,9 endothelial cells , fibroblasts , myofibroblasts , monocytes , and macrophages . it appears that several growth factors10 ( platelet - derived growth factor , tissue growth factor tgf beta1 and 2 , fibroblast growth factor , vascular endothelial growth factor , nerve growth factor ) could stimulate glial cells to transdifferentiate into myofibroblasts and stimulate myofibroblasts to turn on their contractile actions more so in young subjects.911 moreover the role of plasminogen and metalloproteinases in contraction of erm has been raised.12,13 spontaneous release of erm is a rare event but is known to occur in adults and is related to the occurrence of an acute pvd that simultaneously releases the attachment between the retina and erm ( figures 10 , 11 ) . separation or peeling of erm in young subjects is quite rare.1430 it may occur spontaneously by development of a pvd,23 or shortly after panretinal photocoagulation or nd : yag ( neodymium - doped yttrium aluminum garnet ) posterior capsulotomy27 meyer et al15 presented six cases of spontaneous gradual remodeling with release of erm in young subjects . they hypothesized that when the contracting forces of the immature erm are stronger than its adhesions to the retina , the membrane may separate spontaneously . only one of six cases had pvd15 and one case with prior pvd also had release of erm.16 erm release was more common in eyes with pvd:23 in a study of 1,248 consecutive eyes with idiopathic erm followed - up for around 3 years , erm self - separation occurred in 37 eyes ( 3.0% ) , with 16 of 1,091 eyes with pre - existing pvd ( 1.5% ) and 21 of 157 eyes without pre - existing pvd ( 13.4%).23 a higher rate of spontaneous separation was reported in japan : nomoto et al24 detected five patients with spontaneous separation of erm among 92 patients with idiopathic erm . three mechanisms ( figures 1015 ) are proposed for spontaneous erm separation including the two previously described ones : pvd ( figure 11 ) , remodeling ( contraction of myofibroblast ) ( figures 12 , 13 ) , and rupture of weakest line by lifting heavy objects ( valsalva ) ( figures 14 , 15 ) . head - down position combined with weight - lifting ( table 1 ) and mouth closure lead to high intraocular pressure ( iop ) ( rise can reach up to 30 mmhg)31,32 and this places tension on tissues leading to compression of the vitreous against the retinal surface and hence retinal dehiscence in places of retinal lattice or in this case tearing off of the elastic fibrous tissue already under tangential traction at its weakest , thinnest point . valsalva maneuver comprises forcible exhalation against the closed glottis , thereby creating a sudden increase in the intrathoracic or intra - abdominal pressure . ocular and systemic changes are secondary to the extreme pressure elevations that occur in the intra - abdominal , intrathoracic , intracranial , intraocular , and vascular compartments . the enormous pressures generated lead to elevations in intracranial pressure obstructing venous outflow leading to hemorrhage and elevations in iop . in one study by dickerman et al32 iops were significantly elevated by weight - lifting by 15 mmhg from a mean of 13 to a mean of 28 with one subject s iop reaching 46 mmhg during maximal contraction . macdougall et al33 found severe elevations in blood pressure ( bp ) with mean value of 320/250 mmhg ( bp exceeding 480/350 mmhg in one subject ) and mouth pressures of 3050 torr during a single maximum lift ( normal mouth pressure being 15 torr ) . this combination of severe elevation in bp and intracranial pressure would have yielded a high incidence of ocular hemorrhage was it not for the dampening effect of high iop . erm rupture during weight - lifting was not previously reported in the literature ( table 1).3242 the relation between weight - lifting and erm separation could be a coincidence with the natural history of erm taking its course . the current erm is thought to be primary and not secondary to trauma or inflammatory chorioretinal disorders . other factors may be involved in erm separation like rubbing of the eye or minor trauma to the eye , neither of which could be elicited in this case . a table of ocular findings in weight - lifters is enclosed ( table 1 ) . in conclusion , erms in young subjects seems strikingly different from that of those in older individuals ; they appear thicker , whiter with high prevalence of myofibroblast cells , hence the contracting forces that stretch the retina . potential maneuvers that can put stress on erm surface include severe acute oculopression or rubbing that can raise the iop acutely and valsalva maneuvers , hence triggering spontaneous resolution of erm via rupture in its thinnest meridian with subsequent contraction of the thicker side towards the epicenter .

this patient presented for surgery at the age of 32 years , 14 months after his initial complaint of metamorphopsia and visual loss in the right eye . past tests demonstrated a whitish epiretinal membrane ( erm ) with translucent stress lines over a thickened macula . visual acuity was found on last presentation to be normal with minimal alteration on amsler grid testing . a torn erm was found in the center with left - over erm temporally and rolled - over erm nasally at the site of the epicenter with no posterior vitreous detachment . visual recovery occurred gradually over several days 2 months prior to presentation apparently following heavy weight - lifting with a sensation of severe eye pressure . sequential funduscopy and optical coherence tomography scans demonstrated the peeling of an erm accompanied by normalization of foveal thickness . valsalva maneuver had put excessive tension on erm which tore in its center at the weakest line with gradual contraction of the erm away from the fovea towards the peripapillary area . this is a new mechanism of self - separation of erm induced by valsalva . erm in young subjects is subject to rupture and subsequent separation by tangential traction . there are three mechanisms for spontaneous separation of erm : 1 ) posterior vitreous detachment with pulling of erm by detaching vitreous ( most common in adults ) ; 2 ) the contracting forces of the immature erm become stronger than its adhesions to the retina resulting in slow tangential traction on the edges of the erm and gradual separation from the edges towards the center ( remodeling common in youngsters ) ; and 3 ) acute tearing of erm at its weakest central point and retraction of part of the membrane towards the epicenter ( current case report ) .

a 79-year - old male visited our clinic for the evaluation of left ocular pain that had recently worsened . he returned six weeks later with symptoms of mild fever , cough , and chills , as well as left facial erythema , swelling , and tenderness ( fig . 1 ) . we diagnosed the symptoms as orbital cellulitis induced by recent evisceration surgery and the common cold . however , despite two weeks of empirical antibiotic therapy , the patient 's symptoms worsened . an orbital computed tomography ( ct ) scan revealed enhanced soft tissue infiltrations in his left extraconal and intraconal spaces and a thickening of the left eyelid ( fig . an incisional biopsy of the orbital tissue was performed through the superomedial portion of the conjunctiva . the tumor was gray - white colored and was not separated from the surrounding tissue on gross examination . histopathology demonstrated cells with round to oblong nuclei , small distinct nucleoli , and relatively abundant granular amphophilic cytoplasm . some cells had signet ring cytology , with a dominant cytoplasmic vacuole and an eccentrically placed , crescent - shaped nucleus ( fig . immunohistochemistry revealed that the tumor tissue was positive for cytokeratin and cytokeratin 7 but negative for cytokeratin 20 . results of an abdominal ultrasound , abdominal - pelvic ct , and a whole body bone scan suggested no systemic involvement . however , brain magnetic resonance imaging and positron emission tomography revealed metastatic lesions on the left frontal and temporal lobes of the skull ; nasal bone ; left basal skull ; right mandibular ramus and sternum ; vertebra in the cervical , thoracic , lumbar and sacral regions ; and the left ischium ( fig . 4 ) . to rule out a secondary tumor from the previous rectal lesion , rectal biopsy was performed and revealed a benign adenoma confined to the mucosal layer . consequently , the lesion in question was diagnosed as a primary malignant eccrine sweat gland carcinoma of the eye ( a histiocytoid variant of eccrine sweat gland carcinoma ) with multiple bone metastases . although the patient was fully functional on the first visit , his general condition declined during the subsequent three months . the patient became bedridden , refused all recommended treatments , and received only conservative treatment . primary eccrine sweat gland carcinoma is a very rare tumor that most typically occurs in the eyelids of the elderly . there are three variants of this type of carcinoma : mucinous , adenoid cystic , and ductal [ 1 - 6 ] . ductal carcinomas are further classified into two categories based on the type of cell differentiation : well - differentiated ductal carcinoma featuring numerous signet ring cells are classified as signet ring carcinoma , while poorly - differentiated ductal carcinoma is classified as the histiocytoid variant . this histiocytoid variant of eccrine sweat gland carcinoma showed a histiocyte morphology rather than a signet ring cell morphology in the tumor burden , although histiocytoid tumors may contain foci of signet ring cell morphology , and vice versa . tumor cells in this case exhibited eosinophilic cytoplasm with intracytoplasmic vacuolations , characteristics similar to those of a histiocyte . the majority of tumor cells did not have the distinct , eccentric , scimitar - like nuclei of signet ring cells . a primary histiocytoid variant of eccrine sweat gland carcinoma is a very rare neoplasm , with only eight cases having been reported in the literature . in the cases reported , most tumor cells had abundant eosionophilic cytoplasm with intracytoplasmic vacuolations resembling histiocytes and a signet ring appearance . the diagnosis of primary histiocytoid variant of eccrine sweat gland carcinoma is one of exclusion . common primary foci include the breast , gastrointestinal tract , lung , skin , and urogenital tract . previously reported cases of the histiocytoid variant of eccrine sweat gland carcinoma follow an indolent course with slow and painless growth . the case reported here had an unfavorable outcome with rapid progression , ocular pain , facial pain , and multiple bone metastases . most cases of primary eccrine sweat gland carcinoma described in the literature mainly appeared in the eyelid . however , kramer et al . described the eccrine sweat gland carcinoma in the orbit . like kramer et al . , the imaging studies in this case showed soft tissue infiltrations primarily involved in the orbit . moreover , the subcutaneous infiltrations of the eyelid were also noted on the imaging studies . these facts suggested that the tumor mass in this case affected both the orbit and the eyelid . the orbital imaging studies were not performed before the evisceration surgery because it was believed that the patient 's accelerated ocular pain was induced by glaucoma . at his preoperative assessment , after the evisceration surgery , the patient 's facial pain and erythema were believed to be caused by orbital cellulitis . he had multiple risk factors for orbital infection : advanced age , recent evisceration surgery , silicone ball implantation , and symptoms of the common cold . in hindsight , the increased ocular pain could have been caused by the tumor growth occurring at the time of the evisceration surgery , rather than glaucoma . in other words , the ocular pain could have been cancer - related pain associated with the rapid tumor growth . it is difficult to determine the exact time of tumor occurrence because orbital imaging was not performed before the surgical procedure . we presumed that the patient 's pre- and post - operative pain and orbital cellulitis may be related to the tumor growth . furthermore , the rapid progression of the tumor may have been accelerated by the surgical procedure . as a result , the interval from the patient 's initial visit with simple left ocular pain to the eventual diagnosis of primary eccrine sweat gland carcinoma was only three months . after the diagnosis , multiple metastases were also detected along the spine . to our knowledge , this is the first korean case of a histiocytoid variant of eccrine sweat gland carcinoma in the eye . based on this case , we suggest taking an orbital imaging study prior to evisceration surgery in cases of abnormal ocular pain or rapid progression . in refractory cases of orbital cellulitis , aggressive follow - up

a 79-year - old male presented with left ocular pain . evisceration and silicone ball implantation were performed after a diagnosis of phthisis . he returned six weeks later because of left facial erythematous swelling , tenderness , mild fever , chills and cough . his condition was diagnosed as orbital cellulitis . despite two weeks of empirical antibiotic therapy , the symptoms worsened . a subsequent orbital computed tomography scan revealed enhanced soft tissue infiltrations in his left orbit and eyelid . biopsy showed a diffusely infiltrating tumor of signet ring cell cytology . a systemic evaluation revealed multiple bone metastases . based on this evidence , the patient was diagnosed with a very rare case of histiocytoid variant eccrine sweat gland carcinoma with multiple bone metastases .

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

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

dysgenetic polycystic disease ( dpd ) of salivary gland is a rare cystic condition with distinctive histopathology resembling that of polycystic condition affecting the kidneys and pancreas . this disease is thought to be a developmental disorder of the distal ductal system of the salivary gland and is common among women . in this paper a 21-year - old woman came to us with a chief complaint of progressively growing , non - painful swelling near the right ear since 2 years . she complained of a sudden increase in size and associated dull , aching and continuous pain . family history revealed that her mother and elder sister were operated on the lower jaw for multiple cystic lesions , reports indicated they had odontogenic keratocysts . extra - oral examination revealed diffuse swelling on the right side of the face [ figure 1a ] measuring about 3 cm 5 cm extending from tragus of the ear to 2 cm below the angle of mandible superior - inferiorly and anterior - posteriorly it extended between posterior border of mandible and mastoid process . swelling was tender , firm in consistency and fluctuant ; skin overlying the swelling was normal and was not fixed to underlying structures . ( a ) diffuse swelling on the right side of the face extending between the tragus and angle of mandible , ( b ) patient at 18 months follow - up with no evidence of recurrence , shows minimal surgical scar computed tomography scan [ figure 2a ] revealed an enlarged right parotid gland extending into the parapharyngeal region . there were multiple small cystic areas in the gland with one large cystic area in the deep lobe . the entire gland was well - circumscribed with no evidence of infiltration into the surrounding tissue giving the impression of a benign cystic lesion . ( a ) coronal section of computed tomography scan showing enlarged right parotid gland extending into the parapharyngeal region , ( b ) excised specimen showing affected deep lobe of the parotid gland considering the clinical , radiological presentation and presence of multiple cystic spaces in the gland , malignancy was excluded . as the lesion occupied most of the gland , consent was taken from the patient for total parotidectomy under general anesthesia . total parotidectomy with preservation of the facial nerve was performed by modified blair 's incision . the branches of facial nerve were easily separated from the tissue as the lesion was cystic and encapsulated in nature . superficial as well as deep lobes were removed in two portions and were sent for histopathological examination and the surgical defect was reconstructed with posterior belly of digastric flap . post - operatively facial nerve function was normal with mild paralysis of marginal mandibular branch , which recovered after 1 month . excised specimen ( part superficial to the facial nerve ) measured 6.0 cm 4.2 cm 1.8 cm and was dark brown in color , cut surface showed adipose and gland tissue . the part deeper to the facial nerve measured 6.8 cm 5.2 cm 6.0 cm [ figure 2b ] , pale tan to dark brown in color and the cut surface revealed small cystic spaces containing mucin like material . histopathological sections from the superficial part of the gland revealed serous acini and ducts with connective tissue septae separating the parenchyma . histopathological sections from the gland deeper to the facial nerve revealed only multiple cystic spaces of varying diameter ranging from few millimeters to few centimeters in a loose , myxomatous and bland connective tissue stroma [ figure 3 ] . the cystic spaces were lined by a variety of epithelial cells - cuboidal , columnar and squamous cells [ figure 4 ] . they contained watery to pale eosinophillic material in them [ figures 5a and 6 ] . entire parenchyma was replaced by the cystic spaces and connective tissue [ figure 7 ] . immunohistochemical staining for pan cytokeratin ( ck ) , epithelial membrane antigen , progesterone and estrogen receptors were performed and only panck was positive suggestive of epithelial origin of the disease [ figure 5b ] . the patient was followed - up for 18 months with no evidence of recurrence [ figure 1b ] . photomicrograph showing multi - cystic spaces of various sizes lined by epithelium within a bland connective tissue stroma ( h&e stain , 100 ) the epithelium resembles embryonic type of epithelium which lacks a clear basement membrane ( h&e stain , 400 ) ( a ) epithelial lining under high magnification ( h&e stain , 400 ) with bland connective tissue , ( b ) immunohistochemical photomicrograph showing pan cytokeratin expression in the epithelial cells of the cystic spaces ( ihc stain , 100 ) section shows multiple cystic spaces lined by epithelium . salivary gland parenchyma is absent ( h&e stain , 100 ) section shows the entire salivary gland parenchyma replaced by cystic spaces of varying sizes and shapes and loose myxomatous connective tissue stroma which is slightly inflamed . the cystic spaces appear to be lined by single layered flat cells in some areas and hyperplasic in other . spectrum of non - neoplastic diseases of the major salivary glands include acinar / ductal malformations , cysts , sialadenitis , sialolithiasis , sialadenosis , human immunodeficiency virus - associated lympho - epithelial cysts ( lc ) , oncocytosis and sialometaplasia . three benign cysts commonly affect the parotid glands [ table 1 ] they are lc , salivary duct cyst ( sdc ) and polycystic or dysgenetic cyst . polycystic or dysgenetic disease of the parotid gland is the rarest of the non - neoplastic cystic lesions since only 14 cases have been reported in the literature . among all the cases reported in the english literature comparison of clinical features of various parotid salivary gland cysts dpd of parotid was first reported from an analysis of a large series of 5739 cases of salivary gland disorders . because of absence of inflammation in the connective tissue , it is considered to be a developmental disorder arising from the distal duct system of the salivary glands , apparently limited to parotid gland and females with characteristic clinical presentation and distinctive ; if not pathognomonic histopathological appearance . however , there are two reported cases of dpd affecting males and only one case affecting submandibular gland . dpd of parotid resembles the dpd of other parenchymal organs such as pancreas and kidneys and is thought to result from an unknown common embryonic insult with an autosomal dominant pattern of inheritance in females . it presents as bilateral parotid swellings and overt clinical signs are usually delayed even in adulthood . pathogenesis of dpd has been related to disturbance in the ramification and canalization of the ductal system during the second stage of the development of salivary gland that extends to the end of the seventh embryonal month , hence it is thought to be a developmental malformation of the duct system . brown et al . , have reported a case where the swelling worsened with the onset of pregnancy and regressed within 4 - 6 months after parturition . they have speculated that hormonal changes might cause expression or exacerbation of the underlying condition . in the present case , there was a unilateral fluctuating non - tender swelling in the right deep lobe of the parotid gland . the age and sex of the patient correlated with most of the other reported cases . in the absence of the superficial lobe or information about the location of surgery , it would have been difficult to even identify the tissue of origin as salivary gland because the entire deep lobe parenchyma was replaced by multiple cystic spaces interspersed with bland , loose myxomatous connective tissue stroma without any fibrosis . in the entire deep lobe , although the lobular pattern was appreciable the parenchyma was entirely replaced by epithelial lined cystic spaces of various sizes and configuration . the epithelium lining the cystic spaces ranged from flattened cells to cuboidal and columnar with no associated acute or chronic sialadenitis . the cystic spaces showed pale eosinophilic secretions in many places , but no microlith or spherolith formation was seen . because the cystic lesions in the parotid gland may represent an array of diverse entities with different biological behavior , a number of cystic lesions were considered in the differential diagnosis and was narrowed down to two possible lesions namely sdc and sclerosing polycystic adenosis [ tables 2 and 3 ] . we took multiple samples of the specimen again , so as to include all the representative areas to identify , if any mucoepidermoid or adenoid cystic carcinoma like areas , which are known to cause obstruction of the ducts resulting in sdc were present . carcinomatous tissue was not seen in the sections ; hence , a diagnosis of sdc associated with salivary gland carcinoma was ruled out . furthermore , the histopathology did not resemble any type of sdc as described by eversole such as presence of even minimal inflammation , oncocytes , mucous metaplasia and papillary projections which made sdc a less likely diagnosis . absence of fibrosis , hyperplastic ductal and acinar epithelial elements did not favor sclerosing polycystic adenosis , which was excluded based on immunohistochemical markers as well . thus , a final diagnosis of dpd of the parotid gland was arrived at based on extensive involvement and replacement of salivary parenchyma with maintenance of lobular architecture and distinctive features of this disease as described in previously reported cases . histopathological similarities among the three cystic lesions of salivary glands histopathological differences among the three cystic lesions of salivary glands since the present case resembles an autosomal dominant pattern with both mother and sister having been operated for multiple odontogenic keratocysts , the genetic predisposition of this condition can not be ruled out as okc 's are also known to have a genetic predisposition . the same genetic abnormality , which was expressed in the mother and sister as multiple okc 's could have expressed as dpd in the present case . both okc and dpd are developmental cysts in nature while the former is odontogenic in origin , whereas the latter is salivary gland origin . there are many theories , which have been put forward regarding the etiology of this condition such as genetic predisposition , retention of secretion leading to cyst formation and developmental malformation of salivary gland ductal system . in all the previously reported cases of dpd with familial occurrences the cystic lesions were restricted to only salivary glands while in the present case instead of salivary gland genetic abnormality , the condition might have expressed as multiple okc of the lower jaw in mother and sister . in general , lobectomy or superficial however , further development of new lesions or enlargement of residual cystic tissue in the remaining lobes have not been reported . in our case , most of the gland was involved ; hence total parotidectomy with the preservation of the facial nerve was performed , not only for cosmetic purpose but also to relieve symptoms . long - term follow - up is required to rule out recurrence and to screen for the involvement of other salivary glands since very few cases of this nature have been reported in the literature .

dysgenetic polycystic disease ( dpd ) is a rare cystic lesion affecting mainly the parotid salivary glands with only 14 reported cases in english literature . dpd of parotids is more common in females , common in younger age group , mostly bilateral in occurrence and commonly affects the superficial lobe . surgery is performed for symptomatic relief and cosmosis . we report a case of a unilateral dpd of the parotid gland with distinctive histopathology . patient was treated by performing total parotidectomy with preservation of the facial nerve .

childhood morbidity consumes a substantial portion of health care resources in a hospital . the overload in hospital ward remains a major source of concern in many countries , including india , for policy makers . the availability of beds is perhaps the single most important factor in determination of the hospital utilization in a country.(1 ) in india , shortage of hospital beds is a huge problem , the average bed population ratio being 9 per 10,000 population in comparison with the world average of 27 per 10,000 during 2000 - 2009.(2 ) as the demand for health care increases , a high efficiency on limited resources is necessary for affordable high - patient service levels . a possible way to minimize the problem of scarcities of beds is to look for variation in bed utilization by different causes across the country and plan services accordingly . a country needs sound epidemiological information to prioritize , plan and implement the public health care system effectively . morbidity data from hospitalized patients reflect the causes of major illnesses and care - seeking behavior of the community . understanding of hospital burden due to different childhood morbidity could contribute to a more effective approach in designing appropriate service . this information also provides the basis for patient care and bed management in a hospital . there are many factors affecting bed utilization , namely the allocation of beds , patient placement and patient admission policies , etc . bed allocation means assigning beds to various patient categories according to medical speciality , accommodation type , needs of the patient and educational requirements in teaching hospitals along with cost consideration . studies on magnitude and burden of child morbidity in terms of hospital bed utilization are limited . the present study was undertaken with the objective to find out the pattern of hospital bed utilization by different childhood morbidity and length of stay in the hospital . it was a descriptive study with retrospective analysis of records conducted in the in - patient pediatric department of r. g. kar medical college and hospital , kolkata . the study involved the analysis of records of pediatric patients who were discharged from the pediatric department over a period of 12 months from 1 january 2007 to 31 december 2007 . data were retrieved from the admission and discharge registers and , in case of any confusion , bed head tickets were also consulted . this hospital is a government tertiary - level referral center with 60 effective beds in the pediatric department . children under 12 years of age with illness requiring hospitalization are admitted to this pediatric department . pediatricians are available for consultation round - the - clock under the guidance of senior consultants . there is a neonatal care unit that admits babies delivered within the hospital as well as referred from outside . as there is no trauma care or burn unit in this department , all surgical pediatric cases are admitted to the surgery department . children suspected to suffer from cholera or other infectious diseases are not admitted in this hospital ; they are referred to another hospital named infectious disease and beliaghata general ( i d and bg ) hospital for management . before conducting this study , the study was conducted during a period of 2 months from january 2008 to february 2008 . total discharged patients during the reference period of data collection ( 2007 ) were 4008 , out which information on 25 cases was incomplete ; thus , finally , 3983 cases were studied . the investigators abstracted all the children 's medical records from the pediatric department using a pre - designed data collection tool . the information obtained included infant morbidity ( illness or adverse events that lead to hospitalization ) and clinicotherapeutic details ( history of illness , physical examination , laboratory investigation , diagnosis , onset of illness , duration of illness , severity , treatment , complication , treatment outcome and length of stay in hospital ) . the morbidity that co - existed with the principle diagnosis during stay in the hospital or complication developed during management of the case was ignored as diagnosis . this includes the cumulative bed days occupied by all patients during the reference period of study . the maximum number of inpatient days of care that would have been provided if all beds were filled during the year . as the effective beds available in the pediatric department during the study period were 60 , the available bed days would be 60 365 = 21,900 . the occupancy rate is a calculation used to show the actual utilization of an inpatient health facility for a given time period . to calculate bor , we used inpatient days of care and bed days available in this formula : ( inpatient days of care / bed days available ) 100 . this includes the cumulative bed days occupied by all patients during the reference period of study . the maximum number of inpatient days of care that would have been provided if all beds were filled during the year . as the effective beds available in the pediatric department during the study period were 60 , the available bed days would be 60 365 = 21,900 . the occupancy rate is a calculation used to show the actual utilization of an inpatient health facility for a given time period . to calculate bor , we used inpatient days of care and bed days available in this formula : ( inpatient days of care / bed days available ) 100 . of the total admitted cases , about one - third were infants , of which neonatal and post - neonatal age group constituted 45% ( 549/1226 ) and 55% ( 677/1226 ) of the cases , respectively . total admission days in the infancy and 1 - 4 years age group were 8817 days and 8184 days , which accounted for 35.10% and 32.58% of the total days of admission , respectively [ table 1 ] . further analysis revealed that 49% and 51% of the total admission days during infancy were noted in the neonatal and post - neonatal cases , respectively . the average length of hospital stay in the present study was 6.31 days ; the analysis of length of hospital stay by sex indicated that it was a little higher in female subjects ( 6.54 days ) than that in male subjects ( 6.16 days ) . distribution of the study population according to age , sex and occupied bed days the average length of hospital stay during infancy was 6.6 days . table 2 depicts the causes of morbidity in terms of frequency and bed days utilization by causes . of all the causes , respiratory tract infection , including acute respiratory infection ( ari ) , was the leading cause for hospitalization ( 17.52% ) , followed by chronic hemolytic anemia ( cha ) ( 13.93% ) , convulsive disorder ( 13.33% ) , diarrheal disease ( 7.83% ) and accident and poisoning ( 6.38% ) . but , while we analyzed the morbidities by bed utilization , it revealed that the major contributors were respiratory tract infection ( 22.23% ) , followed by convulsive disorder ( 12.67% ) , accident and poisoning ( 6.07% ) , diarrheal disease ( 4.95% ) and cha ( 4.42% ) . we have analyzed the sex distribution of the morbidity profile , which revealed that there was a male preponderance of admission in certain categories of diagnosis in comparison with the overall male proportion of admission . it was observed that proportion of male admissions were 65.38% ( 51/78 ) , 64.03% ( 340/531 ) and 61.98% ( 344/555 ) in tubercular infection , convulsive disorder and low birth weight and malnutrition admission , respectively , which were higher than the average proportion of overall male admission ( 61.11% ; 2434/3983 ) . on the other hand , female admission rate was relatively higher in septicemia ( 45.35 ; 39/85 ) , non - physiological hyperbilirubinemia ( 42.31 ; 22/52 ) and birth asphyxia ( 42.11 ; 32/76 ) in comparison with the average proportion of female admission ( 38.89 ; 2434/3983 ) . the bor in the present study was 114.70 , indicating the overcrowding in the ward . hospitalized morbidity helps us to understand the health care needs of the community , judge the adequacy of health care resources and thus help in planning and efficient bed management in the hospital . a total of 3983 children comprising of 61.12% males and 38.88% females were admitted to the pediatric department , of which about one - third were infants . singhi(3 ) also observed a comparatively higher rate of admission by male children both in tertiary care institute and in community hospital . this could be related to preferential care to male child in the society along with the biological vulnerability of male to infection . male preponderance in admissions was noted in tubercular infection , convulsive disorder and low birth weight and malnutrition , whereas female preponderance in admission was higher with acute conditions like septicemia , non - physiological hyperbilirubinemia and birth asphyxia . in the present study , about one - third of total admissions ( 30.78 ) were during the infancy , but , in terms of bed days occupancy , they accounted for relatively higher proportion of the total days ( 35.10% ) of admission . the neonatal period is the most vulnerable period for infants , which contributed to 45% of the total infant admissions and occupied 49% bed days . the bed days utilized by the 1 - 4 years age group is more or less similar to their proportion of admissions . however , the 5 years and above age group used relatively less proportion of bed days ( 32.32% ) in relation to the percentage of total admission ( 36% ) . this indicates that infants are at greater risk and in need of proportionately greater health care resources for their care . in the present study , we observed higher admission in the neonatal age group in comparison with the observations by other workers.(4 ) the average length of stay per patient in the present study was 6.3 days . different workers reported variable length of stay in their studies ; dharnidharkera(5 ) reported a higher mean length of stay ( 7.9 2.7 days ) and deivanayagam(6 ) noted 5.2 days average length of stay . of all the causes , respiratory tract infection including ari was the leading cause for hospitalization ( 17.52% ) , followed by chronic hemolytic anemia ( 13.93% ) . other researches,(357 ) however , reported diarrheal disease as the most common hospitalized morbidity , followed by respiratory tract infection . this may be due to the fact that cholera and or other infectious diseases are not admitted in this hospital ; they are referred to the infectious disease ( i d and bg ) hospital for management . it is clear from the analysis that respiratory tract infection was the leading cause both in terms of number of cases and utilization of bed days , while cha was the second most common cause of admission , but , in terms of bed days utilization , it ranked fourth from the top [ table 2 ] . this group could have been managed on an outpatient basis and thus would save scare resources . if the hospital authority makes provision for day care to manage these cases , it would allow 4.42% of bed days for alternate use . respiratory tract infection including ari was the leading cause for hospitalization ; these conditions , together with convulsive disorder , consumed significant health resources in terms of bed days utilization . as a result of this study , certain policy changes that should improve the efficiency of bed utilization at the hospital waere identified . thus , an alternative adaptive approach for efficient resource usage by optimization of resource utilization is warranted .

background : childhood morbidity consumes a substantial portion of health care resources in terms of hospital bed utilization , and overload in hospital ward remains a major concern in many countries , including india . a possible way to minimize the problem of scarcities of bed is to analyze the pattern of bed utilization by causes and plan services accordingly.objectives:to determine the burden of pediatric morbidity and utilization pattern of pediatric beds in a tertiary care hospital.materials and methods : a retrospective analysis of pediatric inpatient 's records was conducted over a period of 1 year from 1 january 2007 to 31 december 2007.results:of 3983 total admitted cases , about one - third were infants , of which neonatal and post - neonatal age group constituted 45% and 55% of the cases , respectively . in terms of bed - day utilization , infants , 1 - 4 years and 5 - 11 years age group accounted for 35.10% , 32.58% and 32.32% of total days of admission , respectively . utilization of pediatric beds by major causes of morbidity was respiratory tract infection ( 22.23% ) , convulsive disorder ( 12.68% ) , accident and poisoning ( 6.07% ) , diarrheal disease ( 4.97% ) and chronic hemolytic anemia ( 4.42%).conclusion : a minor change in admission policy through provision of day care unit for management of certain cases would allow efficient use of hospital beds .

in 1988 , call et al.5 ) described clinical and angiographic findings in four patients with thunderclap headache related to reversible vasoconstriction of cerebral arteries . since then , some authors have reported that reversible cerebral vasoconstriction syndrome ( rcvs ) is characterized by severe headaches , often thunderclap nature , with or without acute neurological symptoms , associated with multifocal segmental vasoconstriction of cerebral arteries , which resolve spontaneously within 3 months3 ) . there have been increasing numbers of reports of rcvs , attributed to routine check - up of catheter angiography , magnetic resonance ( mr ) imaging or computed tomography ( ct ) angiography for awareness of angiographic variations . the rcvs has been often manifested hemorrhagic or ischemic stroke including cortical subarachnoid hemorrhage ( sah ) , intracerebral hemorrhage ( ich ) , and cerebral infarction3,6,7,17 ) . however , the gradual emergence or coexistence of cortical sah , ich , and cerebral infarction in rcvs is seldom described . moreover , delayed angiographic diagnosis in rcvs has been reported only a few cases1,14 ) . here , we report a case of sah and ich , and cerebral infarction - associated with delayed diagnosed rcvs which treated with surgical and medical management . a 56-year - old female presented with an acute onset of severe headache after coughing described as " a disaster for the first time in my life " , associated with mild nausea . there was no previous history of migraine or other type of headaches , and she denied any regular medication . initially , head ct scan revealed isolated cortical sah within the sulcus of right high frontal lobe ( fig . no cerebral vasoconstriction , venous sinus thrombosis , cerebral aneurysms or arteriovenous malformations were found on digital subtraction angiography ( dsa ) and ct angiography performed immediately after admission ( fig . after four days , ct angiography revealed multiple segments of irregularity consisting of narrowed areas of both middle cerebral arteries ( m2 tracts ) and right posterior cerebral artery ( p2 tract ) with no evidence of arterial vasoconstriction at proximal cisternal segment indicating sah - related vasospasm ( fig . physical and neurological examination findings were normal , and ophthalmologic examination excluded the possibility of retinal vasculitis or inflammation . blood chemistry workup including coagulation function test , hormonal workup , hepatic and renal function test , and serum immunological screening for rheumatologic disease or vasculitis were all negative or within normal limits . cerebrospinal fluid analysis was near normal except for the presence of red blood cells indicating sah . there was neither leukocytosis nor increased protein levels typical of primary angiitis of the central nervous system ( pacns ) . intravenous nimodipine for vasodilatation with blood pressure control was applied under suspicion of rcvs , and oral analgesics were prescribed for her severe headache . five days later , she suffered deterioration of neurological status , stuporous mental change and motor weakness of the right side extremities after coughing ct scan showed huge intracerebral hematoma on left cerebral hemisphere , opposite to the first sah presentation ( fig . emergent decompressive craniectomy and hematoma removal was performed , and she was transferred to the intensive care unit for close observation . intravenous nimodipine was used for blood pressure control and treatment of rcvs , combined with mannitolization for intracranial pressure control . after 12 day , ct scan showed reduction of cerebral edema and hematoma ( fig . her mental status gradually improved to drowsy , and she was transferred to general ward and then received oral amlodipine mesylate . but , her hemiplegia did not change and motor aphasia was found according to improvement of mental status . she complained intermittent mild headache , improved with analgesics . on day 30 , she was transferred to department of rehabilitation for efficient recovery of motor and speech function . one week thereafter , she experienced sudden - onset headache of moderate degree and nausea not severe than her first symptoms , and brain mri showed hyperintense signals in the pons on diffusion - weighted imaging , which are suggestive of acute to subacute cerebral infarction ( fig . after 6 weeks and 8 weeks on admission , ct angiography and dsa exhibited marked resolution of vasoconstriction ( fig . rcvs is presented radiologically and pathophysiologically by diffuse segmental constriction of cerebral arteries that spontaneously resolves within 3 months3 ) . although rcvs considered idiopathic , more than half of cases occur after exposure to sympathomimetic or serotonergic drugs , postpartum state , and headache disorders3,17 ) . sudden - onset headache is the most frequent clinical presentation and nausea , vomiting , photophobia , seizures , focal neurologic deficits can also occur . persistent neurologic deficits , including hemiplegia , hemianopia , aphasia from stroke or severe sustained cerebral vasoconstriction have also been described9,17 ) . some authors reported that the most important factors influencing outcome are related to complications of intraparenchymal hemorrhage11,13,19 ) . pathophysiologically , there are multiple factors causing hemorrhages including pial vessel rupture or reperfusion injuries due to high pressure in the narrowed vessels ( caused by a sudden increase in blood pressure ) combined with impairment of cerebral autoregulation10,16 ) . however , ischemic complication is developed by involvement of more proximal medium- or large - sized arteries after distal small - sized arteries are affected . segmental constriction of proximal vessels ( vertebrobasilar system ) might have been sustained , and this was progressed to the pontine infarction in the present case , albeit infrequently . spontaneous acute cortical sah observed at the convexity of the brain is a relatively rare entity , seldom described15,18,20 ) . an rcvs accompanying cortical sah is relatively rare , so it can be easily underestimated or missed because of subtle presentation on ct scan . in the current case , clinical , laboratory , and radiologically findings showed no cerebrovascular abnormality in initial examination , so we could not exclude non - vasculitic cause of isolated cortical sah . typically , segmental vasoconstriction in rcvs occurs earlier , but , in this case , angiographic abnormalities developed later , when sah had already occurred . although this delayed appearance of typical angiographic abnormalities was quite rare in rcvs , there is an increasingly description of cases with a delay between clinical onset and angiographic changes1,7,13,14 ) . therefore , meticulous interpretation of radiologic data based on repeated dsa or ct angiography is mandated for the accurate diagnosis . recognition of rcvs as a cause of spontaneous , non - traumatic sah may be confused for aneurysmal sah related vasospasm or primary angiitis of central nervous system ( pacns ) . in rcvs , associated vasospasm may be distinguished from sah related vasospasm : absence of ruptured aneurysm ; disproportionate distribution related to focal blood clot ; segmental vasoconstriction occurring earlier ( < 4 days ) ; prolonged , but reversible aspect of angiographic vasoconstriction3,4,9,10 ) . although the proximal cisternal segments are mainly affected in sah related vasospasm , vascular involvement of rcvs started at small distal arteries progressing to medium- and large - sized arteries . this point may be related to progressive , gradual manifestation of variable disease entity in the present case . differential diagnosis of rcvs including pacns is vague and non - specific , and not straightforward but , affects treatment option which in turn , seriously relates to clinical outcome or complications . moreover , there are many undesirable side effects , for example , adverse effect of drugs ( cytotoxic agents or high dose corticosteroids ) , unnecessary brain parenchymal biopsy , and repetition of expensive laboratory tests1 ) . in addition , pertinent clinical assessment is important for differential diagnosis , which has been reported as acute , self - limited course in rcvs than pacns3,12 ) . however , the result from cerebrospinal fluid study in patients with pacns typically demonstrates pleocytosis with elevated protein levels and leukocytosis4,12 ) . authors reported , calcium channel blockers or short term glucocorticoids medications are reported to be effective for treatment of rcvs4,7,9,11 ) . we used nimodipine via intravenous route after angiographic diagnosis . although headache improved over several days , huge intracerebral hemorrhage occurred in the interim period that requiring surgery . the patient experienced recurrent symptom with pontine infarction , but , tolerated well and gradually recovered . however , if we were familiar with predictable factor to progress a severe presentations or there was prompt diagnosis , intra - arterial administration of calcium channel blockers as vasodilator via endovascular technique might have been effective2,8 ) or played a preventive role against hemorrhagic transformations . hemorrhagic transformations of rcvs can be developed by rupture of arterioles due to vasoconstriction - induced high pressure in narrowed vessels . long - term prognosis of rcvs is determined by the degree and amount of stroke3,11 ) . although ultimately reversible , severe vasoconstriction can lead to large area of hypoperfusion and hemorrhagic infarctions , which can be disabling and fatal . the combination of cortical sah , ich , and cerebral infarction with the course of the time in the present case which were recognized with delayed , angiographic evidence of rcvs , teaches important messages . rcvs should be considered as differential diagnosis of non - aneurysmal sah , especially in isolated cortical sah and repeated angiography is recommended for the diagnosis of this under - recognized syndrome , rcvs .

reversible cerebral vasoconstriction syndrome ( rcvs ) is characterized by sudden - onset headache with focal neurologic deficit and prolonged but reversible multifocal narrowing of the distal cerebral arteries . stroke , either hemorrhagic or ischemic , is a relatively frequent presentation in rcvs , but progressive manifestations of subarachnoid hemorrhage , intracerebral hemorrhage , cerebral infarction in a patient is seldom described . we report a rare case of a 56-year - old woman with reversible cerebral vasoconstriction syndrome consecutively presenting as cortical subarachnoid hemorrhage , intracerebral hemorrhage , and cerebral infarction . when she complained of severe headache with subtle cortical subarachnoid hemorrhage , her angiography was non - specific . but , computed tomographic angiography showed typical angiographic features of this syndrome after four days . day 12 , she suffered mental deterioration and hemiplegia due to contralateral intracerebral hematoma , and she was surgically treated . for recurrent attacks of headache , medical management with calcium channel blockers has been instituted . normalized angiographic features were documented after 8 weeks . reversible cerebral vasoconstriction syndrome should be considered as differential diagnosis of non - aneurysmal subarachnoid hemorrhage , and repeated angiography is recommended for the diagnosis of this under - recognized syndrome .

the availability of ' next generation ' dna sequencers has provided zoologists with unforeseen opportunities to address many basic evolutionary issues and , for those of us whose interests lie beyond the model organisms , these are indeed interesting times . not so long ago the costs of large - scale expressed sequence tag ( est ) analyses were prohibitive , but the recent development of the fast and ( relatively ) cheap 454 , illumina and solid technologies is enabling large - scale transcriptome analysis , and potentially whole - genome analysis , to be applied to a wide range of animals , providing insights into evolutionary issues that were once considered essentially intractable . one important and controversial issue that can now be addressed is the gene complement of urbilateria . it is clear that this ancestor of all bilateral animals had a genome resembling that of a modern vertebrate , but which also contained some genes lost from modern vertebrates , raising the issue of just how many genes were present in the ancestor . in this respect , est studies on lophotrochozoans , such as that reported in a recent paper in bmc evolutionary biology , are proving particularly informative . of the three major divisions within bilateria ( the ecdysozoa , the lophotrochozoa and the deuterostomia ; figure 1 ) , lophotrochozoa , which contains the annelids ( worms ) and mollusks ( including snails ) and various minor phyla , is still only poorly represented in terms of whole genome data . a simplified view of animal phylogeny , showing the taxonomic position of groups and organisms mentioned in the text ( genera are in italics ) . relationships among the non - bilaterian phyla remain controversial , but the topology shown reflects the current consensus . numbers in red are percentages of the total number ( 2,308 ) of pomatoceros ests with matches against specific taxonomic groups . numbers on the boundaries between taxonomic groups are shared exclusively between pomatoceros and those groups , whereas in the cases of non - bilaterians and bacteria / protists the numbers reflect ests shared between pomatoceros , lophotrochozoans and those taxonomic groups . for example , 7% of pomatoceros ests are shared only with lophotrochozoans and deuterostomes , and less than 1% are shared only with lophotrochozoans and non - bilateral animals or with lophotrochozoans and bacteria or protists . over half ( 1,205 ; 52% ) of the total number of pomatoceros ests had no matches in the databases . one implication of work on the annelid platynereis dumerilii is that lophotrochozoans may be less derived ( are more representative of ancestral character states ) than members of ecdysozoa , but it is not yet clear how representative platynereis is . have now analyzed a set of ests from a second and only distantly related annelid , the serpulid pomatoceros lamarckii , which differs from platynereis both morphologically and in lifestyle . platynereis is a free - living predator , whereas pomatoceros lives within a tube that it constructs and captures food from the surrounding waters using a crown of feeding tentacles through which water is filtered . nevertheless , data from the two species lead to the same conclusion , that annelids ( and perhaps lophotrochozoans in general ) are less derived than the insects and nematodes investigated so far . one focus of the paper was patterns of gene sharing and gene loss between pomatoceros and the other major groups of organisms . these figures are summarized in figure 1 : pomatoceros shares a significant number of genes ( 158 ; 7% of the total ) only with deuterostomes and other lophotrochozoans , but a much smaller number ( 23 genes ; 1% of the total ) only with ecdysozoans and other lophotrochozoans . in addition , 11 genes shared only with non - bilaterians were identified , illustrating the ubiquity of gene loss . although the genome of a choanoflagellate ( thought to be the closest living relatives of the animals ) showed us that some ' animal - specific ' genes came earlier in evolution , many other genes really are unique to metazoans , and these include components of several signaling pathways ( such as the wnt , transforming growth factor and nuclear hormone receptor pathways ) . when the genomes of bilaterians are compared with those ( admittedly , as yet few ) available for ' lower ' ( non - bilaterian ) animals , one fact that clearly stands out is that a quantitative leap in terms of signaling molecule complexity preceded the emergence of the cnidaria ( the phylum that includes hydras , sea anemones , corals and jellyfish ) . whereas most or all of the animal - specific signaling systems seem to be present in the genomes of porifera ( sponges ) and placozoa ( placozoans ; very simple animals with only three or four distinct cell types ) , they are much less highly elaborated than in cnidarians or bilaterians . for example , whereas the sea anemone nematostella has 12 wnts , most of which are recognizable as homologs of specific wnt types known from bilaterians , the sponge amphimedon and the placozoan trichoplax each have only three wnts that are not easily assignable . in addition , these lower animals seem to have much less well developed arsenals of signaling molecule antagonists . the situation with respect to transcription factors is a little less clear cut but , for example , the homeobox gene complement of nematostella is much more bilaterian - like than are those of sponges and placozoans . in summary , cnidarians seem to be particularly important in terms of under standing the urbilaterian gene repertoire . there is a widespread perception that ecdysozoans have lost more of the ancestral gene set than have deuterostomes or lophotrochozoans . this notion has its roots in early comparisons ( for example , ) between cnidarians , vertebrates and the model ecdysozoans ( fly and nematode worm ) , which clearly demonstrated that gene loss was much more extensive in drosophila and caenorhabditis than in vertebrates . since that time , genome data have become available for a broader range of species , so to what extent does this generalization still hold ? is it possible ( or meaningful ) to generalize - have ecdysozoans in general lost more genes than lophotrochozoans or deuterostomes , or do we still have too few whole genome sequences to be able to say ? there are now whole - genome data for over 20 insect species ( this includes 12 drosophila species ) and a handful ( 5 ) of nematodes . comparisons between insects and vertebrates ( for example , ) indicate that gene loss is largely a function of rates of evolution and divergence times , and does not discriminate between vertebrates or insects . among insects , drosophila has a particularly high rate of evolution , whereas the beetle tribolium and the honeybee apis have lower rates of evolution and have lost fewer of the ancient genes present in urbilateria . although vertebrates in general have lost fewer ancient genes , the chicken is a clear outlier , having lost more genes in the ' universal single - copy orthologs ' and ' universal multi - copy orthologs ' categories than any of the five insects included in the wyder et al . analysis . moreover , whereas the two caenorhabditis species and the parasitic species brugia malayi and meloidogyne hapla all show the ' typical ' ecdysozoan pattern of extensive gene loss , a fifth nematode species , pristionchus pacificus , is not so reduced . whole genome sequences have been determined for seven genera ( eight species ; two schistosoma species ) , but so far very few large - scale analyses have been published . the idea that the genomes of lophotrochozoans are less derived than those of ecdysozoans comes largely from work on the annelid p. dumerilii , which shows that this organism is closer to vertebrates than to ecdysozoans in intron structure and retention , and in protein coding sequence similarity ( see , for example , ) . the only lophotrochozoans with sequenced and analyzed genomes , schistosoma mansoni and s. japonicum , are both parasitic platyhelminths , which , consistent with other parasites , have undergone extensive gene loss and divergence . thus , they can hardly be considered representative of phyla consisting mostly of free - living forms . there are bound to be derived lophotrochozoans , just as there are derived ecdysozoans and derived deuterostomes . so , although this limited sample of two annelids is consistent with greater gene loss in ecdysozoa than in lophotrochozoa , it is still very early days , and it would be premature to yet draw general conclusions . we await with interest the analysis and publication of more lophotrochozoan genomes , particularly those of free - living flatworms , mollusks , and some of the smaller phyla , such as bryozoans , nemertines and brachiopods . one surprising implication of comparative genomics is that no gene is indispensable ; every animal seems to have lost hundreds of what one might have assumed were ' core requirement ' genes . report that 40% of ancient orthologous genes were lost in a least one of the ten animals included in their analysis ( five insects and five vertebrates ) . one example of loss of a core gene is the case of the toll receptor in hydra magnipapillata . whereas nematostella and other members of the basal cnidarian class anthozoa have a canonical toll receptor , hydra ( which is a member of the more derived class hydrozoa ) has lost this gene . hydra seems to have undergone non - orthologous gene replacement , toll receptor function being fulfilled by two unrelated proteins . evolution sometimes dispenses with whole pathways , for instance the entire dna methylation system in the case of dipterans ( flies and mosquitoes ) . all animals have lost genes , but it does not follow that urbilateria was a monster in terms of gene content . bilaterian animals typically have around 20,000 genes ( range 11,500 to 28,000;meloidogyne to tetraodon ) , but a substantial fraction of these are taxonomically restricted at some level . many of these taxonomically restricted genes are paralogs or highly diverged members of large gene families , generated by duplication events that have occurred at all levels . on the basis of the currently available data , the core bilaterian gene set probably contained fewer than 10,000 genes , the caveat being that the available data are rather limited . taxonomic gaps need to be plugged , and more data for non - bilaterians in particular will be critical in revealing the genomic makings of urbilateria . far too few whole - genome sequences are yet available for firm estimates to be made , but it is clear that there is no need to invoke monsters - either hopeful or hopeless .

expressed sequence tag analyses of the annelid pomatoceros lamarckii , recently published in bmc evolutionary biology , are consistent with less extensive gene loss in the lophotrochozoa than in the ecdysozoa , but it would be premature to generalize about patterns of gene loss on the basis of the limited data available.see research article http://www.biomedcentral.com/1471-2148/9/240 .

cadaver transplant entails a long waiting period which is around 6 months to more than a year at our institute . those who continue to remain on chronic hemodialysis during the interim period frequently experience complications and some succumb to them . this leads to an increasing waiting list and also with the annual incidence rate of ckd 5 patients expected to rise at 5 - 8% the need for alternative viable options has increased . we face a similar scenario at our institute and the patients are offered three options 1 ) abo - incompatible transplant with conventional splenectomy being done in the recipient ( abo - i ) , 2 ) abo - incompatible transplant using rituximab ( abo - r ) and 3 ) paired kidney exchange transplant also known as swap transplant [ the amendments made in the transplantation of human organs act have legalized swapping of vital organs . ] between january 2008 and june 2011 , 7 paired - kidney exchange transplants ( pke ) [ figure 1 , table 1 ] , 14 recipients and 14 donors ( both conventional and unconventional ) and 26 abo - incompatible transplants [ table 2 ] were carried out at our center out of which seven patients received rituximab regimen ( anti - cd20 monoclonal antibody ) which avoided splenectomy in them . pattern of paired - kidney exchange transplantation data for pke transplants patients and their blood groups involved in abo - i transplants evaluation of both the recipients and donors involved standard biochemical , serological and radiological investigations . the donor underwent 64 slice ct angiography with volume rendering for anatomical evaluation . prior to every transplant the donor and the recipient were counseled by the respective surgeons , nephrologists and transplant social workers for potential complications . no objection certificates were received from the authorization committees and only then the transplants were scheduled . the transplants were carried out in a single institute . in case of pke transplants both the recipients were operated simultaneously in different operation theatres and the recipients in abo - i transplants underwent open splenectomy after receiving pneumococcal vaccines prior to the transplant . post - transplant the recipient management protocol remained the same with minor changes related to immunosuppressive therapy . in abo - r transplant the protocol called for a 10 days pretransplant conditioning period starting with one dosage of rituximab and followed by full dose . tacrolimus ( 0.125 body weight in kg ) , mycophenolate mofetil ( 1500 - 3000 mg/ day ) , prednisolone [ ( 30 mg ) 1 day prior to transplant . on the day of transplant 500 mg solumedrol is given which is tapered to 125 mg over 3 days . on day 4 post - transplant prednisolone was started at 1 mg / kg which was tapered @ 5 mg / day till dose of 15 - 30 mg / day depending on the serum creatinine value . the cut - off for anti - a and anti - b titres after plasmapheresis done prior to transplant was between 1:1 to 0 . after the last session , 0.5 the duration of hospitalization were same for all on average : recipients ( 10 - 14 days ) and donors ( 5 - 7 days ) . this included the operative and the perioperative expenditure incurred ( including hospitalization , immunosuppression , plasmapheresis , routine investigations , etc ) for a period of 1 year . the cost borne by the recipient for maintenance immunosuppression and follow - up investigations after 1 year of transplant has not been included . out of 19 recipients 4 expired : 2 due to septicemia secondary to community - acquired pneumonia 4 - 6 months post - transplant , 1 expired due to flaring up of underlying incidentally detected lymphoproliferative disorder b cell lymphoma within a week post - transplant . one recipient suffered from subsequent graft rejection 6 months later and went back to dialysis . he underwent graft nephrectomy within a week of the transplant and subsequently went back to dialysis . one recipient had severe post - transplant coagulopathy immediately the next day after transplant and was managed with intravenous infusion of factor vii . figure 2 depicts graft and patient survival data over a follow - up period of 12 - 18 months . five out of the 19 recipients had subclinical pancreatitis which was suspected when the recipients developed either prolonged paralytic ileus or mild pain in abdomen . jaslok transplant registry 2008 and 2011 ( % ) all six recipients recovered well with an average drop of creatinine of 7.7 ( 8.9 pre - tx to 1 post - tx ) except one who expired due to sepsis secondary to community acquired pneumonia 1 month after transplant . figure 2 depicts graft and patient survival data over a follow - up period of 12 - 18 months . figure 2 depicts graft and patient survival data over a follow - up period of 12 - 18 months . the graft survival and patient survival of abo - i , abo - r and pke transplants 12 - 18 months after transplant were 78.9%:80% , 85.7%:85.7% and 100%:100% , respectively . we believe that cost is one of the important factors needed to be considered in a developing country like ours . the approximate expenditure incurred has been summarized [ table 3 ] . expenditure incurred due to transplant per se , immunosuppression given for the subsequent year post transplant , rituximab & dialysis sessions which the patients underwent prior to transplant were included also . this information added a new dimension for looking at and analyzing the options available for end - stage renal disease patients approximate transplant expenditure out of 19 recipients 4 expired : 2 due to septicemia secondary to community - acquired pneumonia 4 - 6 months post - transplant , 1 expired due to flaring up of underlying incidentally detected lymphoproliferative disorder b cell lymphoma within a week post - transplant . one recipient suffered from subsequent graft rejection 6 months later and went back to dialysis . he underwent graft nephrectomy within a week of the transplant and subsequently went back to dialysis . one recipient had severe post - transplant coagulopathy immediately the next day after transplant and was managed with intravenous infusion of factor vii . figure 2 depicts graft and patient survival data over a follow - up period of 12 - 18 months . five out of the 19 recipients had subclinical pancreatitis which was suspected when the recipients developed either prolonged paralytic ileus or mild pain in abdomen . all six recipients recovered well with an average drop of creatinine of 7.7 ( 8.9 pre - tx to 1 post - tx ) except one who expired due to sepsis secondary to community acquired pneumonia 1 month after transplant . figure 2 depicts graft and patient survival data over a follow - up period of 12 - 18 months . figure 2 depicts graft and patient survival data over a follow - up period of 12 - 18 months . the graft survival and patient survival of abo - i , abo - r and pke transplants 12 - 18 months after transplant were 78.9%:80% , 85.7%:85.7% and 100%:100% , respectively . we believe that cost is one of the important factors needed to be considered in a developing country like ours . the approximate expenditure incurred has been summarized [ table 3 ] . expenditure incurred due to transplant per se , immunosuppression given for the subsequent year post transplant , rituximab & dialysis sessions which the patients underwent prior to transplant were included also . this information added a new dimension for looking at and analyzing the options available for end - stage renal disease patients approximate transplant expenditure ckd 5 patient who wants kidney transplant has to find a suitable living donor or wait for cadaver kidney . in parts of india , where cadaveric transplant programme has not taken off fully , when a patient with end - stage renal disease ( ckd 5 ) decides to opt for undergoing transplant he looks for a compatible donor mostly in his own family . the search comes to a standstill when he is unable to find one due to abo incompatibility in the donor . cadaver transplant entails a long waiting period which is around 6 months to more than a year at our institute . those who continue to remain on chronic hemodialysis during the interim period frequently experience complications and some succumb to them . we found that the graft and patient survival in an abo - i transplant with conventional splenectomy is relatively poor as compared to others . abo - i transplants were associated with morbidity secondary to splenectomy , which the recipient had to undergo prior to the transplant , let alone the repeated plasmapheresis and the risks involved . also those recipients who developed pancreatitis probably did so following minor trauma to the pancreas during splenectomy . these patients settled with conservative management . to avoid the morbidity following splenectomy we started including rituximab as a part of protocol for the abo - i tx and the results are encouraging . have upheld rituximab as a viable and safe option for those who undergo abo - i transplants . showed good results at par with the results found in world literature [ figure 3 ] . pke also includes going through the process of obtaining permission from the authorization committees of respective state legislatives which may take time which can amount to weeks , sometimes months in developing countries like india . many countries after a lot of hesitation resorted to pke transplants to meet the donor deficit , including south korea , switzerland and usa . pke ransplant : comparative data interestingly the patient and graft survival of abo - r and pke transplants have been parallel to the conventional transplants which is encouraging . . it also requires more than one team for simultaneous surgery in two donors and two recipients . in a smaller unit cost factor always place a vital role in decision making even if it involves important health issues . however , the abo transplants with or without the use of rituximab raises the cost a bit more due to splenectomy , plasmapheresis and rituximab itself but , we guess it is insignificant if we are looking at improving the graft outcome and the qol of the patient . on an average dialysis costs around 55,000 rupees for 3 months . instead if the recipient can be counseled and is willing he can be encouraged to undergo transplant using rituximab . it would save him from the morbidity associated with dialysis at a very small price . pke are just like any other conventional transplant but it entails 1 ) eligible pair availability , 2 ) state legislative permission which would take a long time , 3 ) a large pool of recipients and donors to choose from and most importantly 4 ) more than one transplant teams . abo - i using conventional splenectomy is a less costly venture needing a smaller unit but the associated risks/ complications is something to reckon with . on the other hand abo - r transplant using rituximab is a viable option in a smaller unit. using rituximab is no doubt a costly venture but it spares the recipient of the associated morbidities of undergoing second surgery i.e. , splenectomy and also of its indolent risks . also the results are encouraging . showed good results at par with the results found in world literature [ figure 3 ] . pke also includes going through the process of obtaining permission from the authorization committees of respective state legislatives which may take time which can amount to weeks , sometimes months in developing countries like india . many countries after a lot of hesitation resorted to pke transplants to meet the donor deficit , including south korea , switzerland and usa . pke ransplant : comparative data interestingly the patient and graft survival of abo - r and pke transplants have been parallel to the conventional transplants which is encouraging . it also requires more than one team for simultaneous surgery in two donors and two recipients . in a smaller unit cost factor always place a vital role in decision making even if it involves important health issues . however , the abo transplants with or without the use of rituximab raises the cost a bit more due to splenectomy , plasmapheresis and rituximab itself but , we guess it is insignificant if we are looking at improving the graft outcome and the qol of the patient . on an average dialysis costs around 55,000 rupees for 3 months . instead if the recipient can be counseled and is willing he can be encouraged to undergo transplant using rituximab . it would save him from the morbidity associated with dialysis at a very small price . on comparing each option and looking at the pros and cons of each . pke are just like any other conventional transplant but it entails 1 ) eligible pair availability , 2 ) state legislative permission which would take a long time , 3 ) a large pool of recipients and donors to choose from and most importantly 4 ) more than one transplant teams . abo - i using conventional splenectomy is a less costly venture needing a smaller unit but the associated risks/ complications is something to reckon with . on the other hand abo - r transplant using rituximab is a viable option in a smaller unit. using rituximab is no doubt a costly venture but it spares the recipient of the associated morbidities of undergoing second surgery i.e. , splenectomy and also of its indolent risks . also the results are encouraging . the inclusion of rituximab in the transplant protocol holds good promise for the future of abo incompatible transplants . the existing donor shortage ( especially due to incompatibility between recipient and donor ) the limiting factor for abo - r and pke transplants in a country like india is time and cost , respectively .

introduction : the options available to ckd 5 patients with donor shortage due to incompatibilities is to either get enlisted in cadaver transplant program or opt for three other alternatives viz ; abo - incompatible transplant ( abo - i ) , abo - incompatible transplant with rituximab ( abo - r ) or paired - kidney exchange transplant ( pke ) . at our institute we have performed abo - i , abo - r and pke transplants and we are presenting the results of these transplants performed at our institution . here , we report our experiences of living donor kidney transplantation in highly sensitized patients.objective:to review the options available to ckd 5 patients with incompatible donor.materials and methods : between january 2008 and june 2011 , 7 pke , 26 abo - i and 7 abo - r transplants were carried out at our institute . evaluation of both the recipients and donors involved biochemical , serological and radiological investigations . in case of pke , recipients were operated simultaneously in different operation theaters . in abo - i splenectomy was done while in abo - r was given . post - transplant the recipient management protocol remained the same . expenditure following each transplant was calculated.results:the graft and patient survival of abo - i , abo - r and pke transplants 12 - 18 months after transplant were 78.9%:80% , 85.7%:85.7% and 100%:100% , respectively.conclusions:the inclusion of rituximab in the transplant protocol appears promising . the existing donor shortage could be addressed by encouraging other options like pke . the limiting factor for abo - r and pke transplants is time and cost , respectively . the decision depends on the informed consent between the patient and the nephrologists .

nowadays , cardiovascular diseases are amongst the major causes of mortality and morbidity worldwide . in iran , like other parts of the world , studies demonstrate that death toll related to cardiovascular complications is high ( 1 ) . according to the reports by the iranian ministry of health 39.3% of the deaths in 2005 were due to cardiovascular diseases . atherosclerosis , a multifactorial disorder , is one of the major causes of stroke and myocardial infarction ( 2 ) . several causes have been described to be associated with the increased risk of acquiring atherosclerosis . these include high fat diets , hypertension , genetic risk factors , and using some medications such as anticonvulsants ( 3 - 6 ) . it has long been believed that cholesterol level is responsible for developing atherosclerosis , but currently researchers identified oxidized fats to be major contributors of atherogenesis ( 7 ) . plasma oxysterols are indicator of lipid oxidative stress and major oxidized bioactive lipids , produced during low density lipoprotein ( ldl ) oxidation . their coalescence in blood vessels causes cytotoxicity , apoptosis , monocyte differentiation and formation of cell foam and consequently damage and malfunction of vascular endothelium ( 8 , 9 ) . they appear to be implicated in the activation of mitochondrial pathway of apoptosis and inflammatory and immunological pathways ( 10 - 12 ) . elevation of the plasma level of oxysterols has been observed in the patients with atherosclerosis and directly correlates with the advancement of atherosclerosis in affected areas ( 9,13 ) . in 2009 ( 14 ) defined six steps for the atherosclerotic effects of oxysterols : 1 ) endothelial cell malfunction , 2 ) increase of cellular adherence and secretion of chemicals which attract the monocytes to the endothelium , 3 ) production of foam cells , 4 ) overproduction of extracellular matrix components and increasing the interaction between cells and macrophages , 5 ) inflammation and formation of fibrotic cup and 6 ) cellular apoptosis . studies by liu et al . and rosklint et al . demonstrated that 25-hydroxycholesterol induce the production of interleukin-18 and interleukin-1 by macrophages and contribute to the inflammation and sclerogenesis in the arteries ( 15,16 ) . in 2007 , arca et al . showed that oxysterols are present in hyperlipidemic patients in high levels ( 17 ) . in 2008 , szuchman et al . demonstrated that oxysterols are highly elevated in the serum of patients with diabetes and hypercholesterolemia when compared to control groups ( 18 ) it appears that oxysterol and its isomers are important atherogenic risk factors due to their high cytotoxicity . in the current research we studied the level of plasma oxysterols in patients with severe coronary artery stenosis and the effects of treatment with atorvastatin . fifty eight patients referred to the taleghani hospital were studied in this cross - sectional study . patients included those suffering from stable angina or coronary artery stenosis , as determined by angiography and were under treatment . patients with coronary artery stenosis were referred to the emergency ward and admitted to the ccu for acute coronary syndrome ; this group was also examined by angiography . study protocol was approved by the ethics committee of the shahid beheshti university of medical sciences . study was performed in compliance with the ethical guideline of the helsinki declaration for medical research involving human subjects . two milliliters of blood was obtained from arterial sheath from patients being examined by angiography and two milliliters of venous blood was obtained from those who had been examined previously . blood samples were transferred to the laboratory at endocrinology and metabolism research center at taleghani hospital . level of 25-oxysterol was measured by the enzyme - linked immunosorbent assay ( elisa ) method ( cusabiotech , wuhan , china ) . these patients were divided into two groups , one were receiving statins at the time of study and one not receiving them . as the distribution of the data was normal ( based on kolmogorov- smirnov test ) , the quantitative data were presented as mean sd and charts . student s t - test was used to compare the means of two groups and one sample t - test was used for the comparison of the means of numerical data from population with the expected value of the normal population . for analysis of qualitative data , fifty eight patients referred to the taleghani hospital were studied in this cross - sectional study . patients included those suffering from stable angina or coronary artery stenosis , as determined by angiography and were under treatment . patients with coronary artery stenosis were referred to the emergency ward and admitted to the ccu for acute coronary syndrome ; this group was also examined by angiography . study protocol was approved by the ethics committee of the shahid beheshti university of medical sciences . study was performed in compliance with the ethical guideline of the helsinki declaration for medical research involving human subjects . two milliliters of blood was obtained from arterial sheath from patients being examined by angiography and two milliliters of venous blood was obtained from those who had been examined previously . blood samples were transferred to the laboratory at endocrinology and metabolism research center at taleghani hospital . level of 25-oxysterol was measured by the enzyme - linked immunosorbent assay ( elisa ) method ( cusabiotech , wuhan , china ) . these patients were divided into two groups , one were receiving statins at the time of study and one not receiving them . as the distribution of the data was normal ( based on kolmogorov- smirnov test ) , the quantitative data were presented as mean sd and charts . student s t - test was used to compare the means of two groups and one sample t - test was used for the comparison of the means of numerical data from population with the expected value of the normal population . for analysis of qualitative data , in the current study , 85 patients suffering from severe coronary artery stenosis were included . mean age of the subjects was 64.4 years ( ranging from 40 to 87 years ) . about 58 ( 68% ) patients were suffering from acute angina pectoris and 27 ( 32% ) from chronic angina pectoris . forty two ( 49.4% ) patients were smokers and 3 ( 3.5% ) had the history of stroke . no significant correlation between plasma oxysterols and smoking or history of stroke was observed ( p>0.05 ) , while taking atorvastatin was significantly correlated with plasma oxysterol levels ( p<0.001 ; table 1 ) . patients having history of receiving atorvastatin , but not taking medication in the study time , had significantly lower plasma oxysterol levels ( p<0.05 ; table 2 ) . this amount is significantly higher than that of the normal population which is estimated to be about 13.1pmol / ml . interestingly , when they were assigned in quartiles , the mean level of first quartile ( 22.2pmol / ml ) is significantly higher than the mean of the normal population ( 13.1pmol / ml ) . mean level of oxysterol was significantly lower in patients receiving atorvastatin ( p<0.05 ) . studying the molecular changes during atherosclerosis has always been important . in the current research we studied the plasma level of oxysterols , specifically 25-hydroxysterol as important derivatives of cholesterol metabolism , and its relationship with consumption of atorvastatin for the first time in iranian population . our research demonstrated that patients with more than 75% stenosis of coronary artery had higher level of plasma oxysterol . cut - off for normal level of oxysterol in our population was 13pmol / ml ( 19 , 20 ) . in our study , all patients with 75% coronary artery stenosis had plasma oxysterol levels higher than 13pmol / ml . low standard deviation proves high sensitivity of our measurements . in the study sample , minimum level of oxysterol was 19.37pmol / ml , and the maximum observed level was 29.84pmol / ml . kummerow et al . reported higher level of oxysterols in the plasma from coronary artery bypass grafting ( cabg ) patients compared to healthy age- and sex - matched controls . according to their study the concentration of sphingomyelin in the arterial cell membrane was directly correlated with the level of oxysterol in the plasma of patients suffering from severe atherosclerosis . this is expected to increase calcium influx required for producing the calcified type vii lesions in the coronary arteries ( 21 ) . in 2008 , a study by endo et al . revealed that increasing the concentration of 7-ketosterols they demonstrated that oxysterols are amongst the major causes of oxidation of low density lipoproteins ( ldls ) and are implicated in the atherosclerosis process and , hence , development of cardiovascular diseases ( 22 ) . findings of the current research are in compliance with hodis ( 23 ) , zeiden ( 24 ) and colles ( 25 ) . investigations by hodis in 1991 and zeiden in the same year in coronary artery patients revealed the role of oxysterols in degenerative diseases ( 23,24 ) . yasunobu et al . in 2001 demonstrated that coronary atherosclerosis is a reflection of oxysterols and the presence of auto - antibodies against ldl . salonen et al . confirmed the relationship between oxysterols and the increase of carotid wall thickness ( 26 ) . another study by qi zhou et al . in 2000 showed that oxysterol level was higher in patients with more than 80% coronary stenosis ( 27 ) . marcello arca et al reported that the level of oxysterol in familial combined hyperlipidemic ( fchl ) patients decreases with the use of anti - hyperlipidemic drugs ( 28 ) . according to the data from current study using statins . level of oxysterol in patients receiving atorvastatin was significantly lower than patients not using it ( 24.4pmol / ml vs. 26.3pmol / ml ; p<0.001 ) . demonstrated that fluvastatin , another member of statin family , reduce the production of oxidizing radicals ( 29 , 30 ) . in the study by giroux et al . it was demonstrated that simvastatin reduce the production of superoxide anions in a dose dependent manner ( 31 ) . in a study by vasanahari et al . it was demonstrated that treatment with statins reduces the level of oxysterols in patients by 24% when compared to control untreated group ( 32 ) . in the current study treatment by atorvastatin reduced the plasma oxysterols level from 26.41.6pmol / ml to 24.42.1pmol / ml ( p=0.001 ) . in this study mean level of oxysterol was 24.82.17pmol / ml which is significantly more than the normal population s mean ( 23.1pmol / ml ) . interestingly , when the samples were divided into quartiles , the mean plasma level of oxysterols in the first quartile ( 22.2pmol / ml ) was significantly higher than population mean . among the variables studied in the current study like cva , smoking and receiving atorvastatin , oxysterol level was significantly reduced in those receiving atorvastatin . contradictory results were achieved by greet van poppel et al . in 1997 demonstrating no relationship between plasma oxysterol levels with the risk of developing atherosclerosis ( 33 ) . although some risk factors did not show significant differences between two groups , clinical significance must be kept in mind in the interpretation of the results as an important factor . patients with acute angina pectoris were having higher levels of oxysterols compared with patients with stable angina pectoris ( 25pmol / ml vs. 24.2pmol / ml , respectively ) but the difference was not statistically significant ( p=0.231 ) . our study provided insight into the involvement of plasma oxysterols in the risk of developing coronary stenosis and the potential of atorvastatin for reducing plasma oxysterol level . considering the experimental evidence regarding the adverse effects of oxysterols on endothelial cells in in vitro studies , results appear sound . however , due to some limitations due to study design , lack of controls and long term follow - up , our data could not be regarded as conclusive and further controlled trials are required for proving the findings . in sum , the results showed that the level of plasma oxysterols is directly correlated with the advancement of coronary stenosis and its stage . it appears that treatment with atorvastatin reduces the level of plasma oxysterols and the risk of stenosis . however , due to some limitations in the current study conducting controlled trials with larger sample sizes to prove this effect of atorvastatin is recommended .

background : considering the increasing incidence of coronary artery stenosis and its related complications , the importance of its etiology and inconsistent reports we aimed to determine the relationship between oxysterol , serum levels and severity of coronary atherosclerosis and effect of statins onoxysterol . methods : a total of 85 patients referred to taleghani hospital , tehran , iran during 2011 - 2012 withcoronary artery stenosis more than 75% , as determined by angiography , participated in the currentstudy . their demographic information and history of smoking and taking atorvastatin was carefullyrecorded . two milliliters of venous blood was obtained from each patient . the serum oxysterol levelof samples was measured using the enzyme - linked immunosorbent assay ( elisa ) method . statisticalanalysis was performed using spss v.19 . results : eighty five patients completed the study . mean age of patients was 64.4 years ; 51 ( 60%)were male ; 55 ( 68% ) had acute coronary syndrome and 30 ( 32% ) had chronic stable angina.meansd of plasma level of oxysterol was 24.80.2 pmol / ml . the normal range of oxysterol levelwas 13pmol / ml . meansd of plasma oxysterol level in patients under statin therapy was 24.42.1pmol / ml . in patients without receiving statins , plasma oxysterol level was 26.381.6pmol / ml . conclusion : findings of the present study indicated significant correlation between serum oxysteroland severity of coronary artery stenosis . it also demonstrated that receiving atorvastatin is associatedwith significant reduction of plasma oxysterol level .

chewing gum is a habit practiced regularly by a relatively high proportion of individuals in many countries including india , and its use has increased within the last decade . in 1999 , available data suggested that some 374 billion pieces of chewing gum were sold worldwide , representing approximately u.s . besides the obvious pleasant taste imparted by flavors and sweetening agents in chewing gum , the practice has the potential to benefit oral and dental health . the introduction of sugar - free or sorbitol - containing chewing gums renewed interest in this aspect of diet , and caries reduction with sugarless and sugar phosphate products was reported by finn and gimision . short - term plaque studies on the other hand demonstrated that sugar - free gums neither altered plaque accumulation nor removed established plaque . mechanical supragingival plaque control is the most rational and efficient method for the prevention of periodontal diseases . daily removal of plaque by the patient is also of concern for a beneficial long - term treatment outcome . the majority of individuals find difficult or impossible to comply with a proper oral hygiene regimen . moreover , even in those patients who do achieve high levels of oral cleanliness , plaque control deteriorates over time . the effective use of mechanical devices to reduce dental plaque , in fact , is highly dependent on compliance with oral hygiene instructions given by dental professionals . reasons for non - compliance are many and may include level of education , domestic circumstances , disposable income , beliefs and attitudes regarding personal and oral care , stressful life events , psychomotor skills , frequency of dental visit , and age . thus , a need exists for adjunctive methods of mechanical plaque removal that are simple , inexpensive , and convenient for use by patients . in the last decade , sugar - free chewing gum has been claimed to provide oral health benefits , including caries reduction and plaque control . the caries preventive effects of these products have been well documented in many experimental and clinical investigations . the mechanical cleaning effects of chewing gum have also been studied , but the results on the antiplaque efficacy , particularly at the smooth ( buccal and lingual ) surfaces of the teeth , have been equivocal . indirect effect of chewing gums to oral health could be through salivary flow stimulation and mechanical tooth cleaning . supragingival plaque is exposed to saliva and to the natural self - cleansing mechanisms existing in the oral cavity . the maintenance of an effective plaque control is the cornerstone of any attempt to prevent and control periodontal disease . the aim of this study was to investigate the effects of sugar - free and sugar - containing gums on both plaque formation and established plaque over the whole surfaces of the teeth . a concurrent parallel double blind randomized control trial was designed involving 16 subjects ( 11 female and 5 male students ) from a dental college , aged 20 to 25 years , who volunteered to participate in this 4-day plaque regrowth study . the subjects were selected on the basis of definite inclusion criteria of having 20 healthy natural teeth free from conservative restorations . exclusion criteria included with no signs of periodontitis , temporomandibular joint disorder , malocclusion , or xerostomia and no medical or pharmacotherapy history that could affect the result of the study . the subjects who could not fulfill the set inclusion criteria the total sample size of 16 was deliberately taken with the help of similar studies conducted around the world considering a total of 11 samples by hanham and addy , 12 samples by pizzo et al . , 10 samples by addy et al . , and 12 samples by pizzo et al . along with this , a pilot study was conducted on six samples ( each n = 3 ) ; based on pilot study , sample size was calculated . the study was powered ( 85% ) to detect a difference in means of 2 units on the primary outcome variable using a 2-sided significance level t - test ; therefore , a total of 16 subjects were recruited for the present study . the subjects who have given the consent and satisfied the criteria of the study were given a through prophylaxis , polishing , and flossing in order to obtain zero baseline plaque , and randomly allocated into group a ( sugar containing ) and group b ( sugar - free ) of eight each . participating subjects were supplied with chewing gums which were similar in appearance and sufficient in quantity for the complete study period . the gums were provided in unmarked boxes , each coded with the subject 's identity and the study period , along with verbal and written instructions on their use . the products tested are shown in table 1 , together with the active ingredients and the manufacturers . they were asked to chew one piece of chewing gum for 30 minutes 3 times a day after meal and to suspend all oral hygiene practices like brushing , mouth rinsing during the study period . chewing gums , active ingredients , and manufacturers the subjects were also requested to maintain their customary dietary habits , but during the first hour after a chewing gum they avoided eating and drinking . on the 5 day , subjects were scored for plaque with the help of silness and loe index . the scoring criteria : ( silness and loe 1964 ) . 0 no plaque1 a film of plaque adhering to the free gingival margin and adjacent area of the tooth . the plaque may be seen in situ only after application of disclosing solution or by using the probe on the tooth surface.2 moderate accumulation of soft deposits within the gingival pocket , or the tooth and gingival margin which can be seen with the naked eye.3 abundance of soft matter within the gingival pocket and/or on the tooth and gingival margin . a film of plaque adhering to the free gingival margin and adjacent area of the tooth . the plaque may be seen in situ only after application of disclosing solution or by using the probe on the tooth surface . moderate accumulation of soft deposits within the gingival pocket , or the tooth and gingival margin which can be seen with the naked eye . abundance of soft matter within the gingival pocket and/or on the tooth and gingival margin . the scores of the sugar and sugar - free chewing gum group were analyzed by using all the data collected were tested for normality before entering for analysis using spss 11.0 version software . the study design was approved by the local ethical committee and conformed to the requirements of the declaration of helsinki as adopted by the 18 world medical assembly in 1964 and subsequently revised . there has been higher mean scores for upper and lower arch by sugar - containing gums ( 1.39 and 1.05 ) when compared with sugar - free gums ( 0.98 and 0.96 ) . and , similar results were found when the total mouth pi scores were compared between the two gums , i.e. , 1.22 and 0.97 , respectively . result difference was statistically significant when tested among the sugar - containing and sugar - free gums of upper arch . mean pi scores in relation to upper and lower quadrant in sugar containing and sugar - free gums ( mann - whitney u test ) in table 3 , the mean pi scores among the anterior and posterior arches when tested for the sugar - containing and sugar - free gums revealed higher mean pi scores for sugar - containing gums , i.e. , 1.10 and 1.32 , among anterior and posterior arches , respectively . comparison of mean pi scores in anterior and posterior quadrant in relation to sugar containing and sugar - free gums ( mann - whitney u test ) in table 4 , the mean pi scores for upper and lower left quadrant were found to be lower in comparison to the upper and lower right quadrant . and , higher mean pi scores were reported in sugar - containing gums of all the four quadrants , i.e. , 1.37 , 1.42 , 1.12 , and 0.98 , respectively . significant difference has been shown for upper left quadrant between the sugar - free and sugar - containing gums . comparison of mean pi score in all four quadrants in relation to sugar containing and sugar - free gums ( mann - whitney u test ) in table 5 , the mean pi scores were found to be lower in upper lingual teeth ( i.e. , 0.65 ) in comparison with buccal and lingual surfaces of upper and lower arches . comparison of mean pi scores buccal and lingual surfaces in relation to sugar containing and sugar - free gums ( mann - whitney u test ) the chewing gum is a common habit in many countries and belief exists amongst the general public that as with fibrous foods , chewing gum has cleansing effect on the teeth and gingiva . some support for mechanical cleansing by chewing gum can be found in earlier reports . despite the lack of evidence for long - term benefits of chewing gum on dental health , some short - term advantages resulting from the mechanical removal of debris may be derived . with such objectives to test the efficacy of chewing gum containing sugar or sugar free in a 4-day double blind study , the results showed that there is minimal difference between the sugar - free and sugar - containing gums . this indicates that sugar - free and sugar - containing gums do not have much effect on plaque accumulation . there was no significant reduction in plaque accumulation with sugar - containing chewing gums in the present study . such results have been supported by other authors such as bratthall and ainamo et al . the reduction in plaque reported may be due to the mechanical forces that little amount of plaque is removed henceforth . gum chewing elicits an increase in saliva flow rate which increase the buffering capacity of saliva and concurrently leads to an enhanced clearance of fermentable carbohydrates from the mouth . the low scores recorded lingually on the lower teeth and palatally on the upper teeth in the present study would suggest that natural cleansing mechanisms of foods do alter plaque coverage of tooth surfaces and similar results were found in the another study . nevertheless , since no detrimental effects of chewing gum on the incidence of caries have been reported in the present study and since sugar - free chewing gum may actually reduce the incidence of caries , the chewing of gum can not at this time be considered a hazard to dental health . however , it is still tempting to concur with the suggestions of ainamo et al . that people who chew gum should be encouraged to use the now readily available sugar - free gums . such preparations may also act as suitable replacements for other confectionary of known cariogenic potential . based on the available evidence , the chewing of sugar - free gum after meals has been recommended as a way to prevent caries , even if no mechanical oral hygiene can be performed . similar studies done on plaque control other than chewing gums employing fibrous food such as carrot have been undertaken by lindhe and wicen and reece and swallow . it is concluded from these studies that chewing gum is capable of removing plaque deposits from the more exposed aspects of tooth surfaces and will reduce the presence of salivary debris immediately after eating food .

background : chewing gum is a habit practiced regularly by a relatively high proportion of individuals in many countries including india , and its use has increased within the last decade . the aim of this study was to determine the effects of sugar - free and sugar chewing gums on plaque deposition.materials and methods : the study is a double blind clinical trial involving 16 healthy volunteers ( divided into 2 groups ) in a 4-day plaque regrowth model . on day one , subjects received professional prophylaxis , suspended oral hygiene measures , and commenced chewing their allocated product . gum chewing was one piece chewed for 30 minutes 3 times a day . on day 5 , subjects were scored for plaque with the help of silness and loe index.results:results show sugar - free group have a lesser mean plaque score of 0.98 as compare to sugar group ( 1.23 ) , though this difference was not statistically significant.conclusion:the sugar - free gums can be used as an adjunct to mechanical oral hygiene measures .

the eu - doped yttria ( y2o3 ) is one of the most popular red phosphors commonly applied in different light - emitting devices ( hunt and chakhovskoi 1997 ; shea 1998 ) . the eu : y2o3 phosphor is used for wide group of light sources and displays ( hunt and chakhovskoi 1997 ; shea 1998 ; shionoya and yen 1998 ; srivastava and ronda 2003 ; vetrone et al . 2010 ; chen et al . 2005 ; hreniak et al . 2004 ; jang et al . 2006 ; lee and choi 2005 ; pechini 1967 ; tang et al . 2003 ; song et al . 2003 ; vollath and szabo 2006 ; xu et al . the simple one is modified pechini method ( pechini 1967 ; psuja et al . 2007a , b , 2009 , 2012 ) . the disadvantage of this method is the necessity of sintering of resins which implicates the difficulties in the case of mass production . those difficulties come off as a large amount of air contaminations products of thermal decomposition of resins . another drawback of this method is violence of reaction , which really influence and limit mass production application . despite the above - mentioned methods ( hreniak et al . 2004 ; lee and choi 2005 ; pechini 1967 ; xu et al . 2005 ; song et al . 2011 ; jang et al . 2006 ; tang et al . 2003 ; vollath and szabo 2006 ; zhang et al . 2004 ) synthesis of nanocrystals using only water solutions of nitrates exposited for non - thermal plasma ( ntp ) is possible . the other method of synthesis of nanoparticles uses a plasma microwave reactor ( vollath and szabo 2006 ) , where the reaction of ionized gases takes place . in the present work a new method of synthesis of eu : y2o3 nanocrystals using ntp reactor this method allows fabrication of nanoparticles with narrow size distribution by using only water solutions of metal nitrates . the plasma treatment is necessary to change the crystallization mechanism of salts ( nitrates ) dispersed in the solution . such a process of fabrication of nanostructures has been described earlier by ( tereshko et al . the nitrides were prepared by dissolving the corresponding lanthanide oxides in a nitric acid solution and the water was evaporated from the solution . the structure of obtained powders samples was characterized by x - ray diffraction ( xrd - a stoe powder sensitive detector ; filtered cuk1 radiation ) . for eu : y2o3 sample sintered at 600 c tem images was created using philips cm 20 super twin transmission electron microscope with resolution 0.025 nm . the photoluminescence spectra were registered at room temperature using ccd spectrophotometer avantes 3501,000 nm spectral range , ~0,35 nm resolution . the samples were excited using ex = 266 nm of nd : yag laser system ( the forth harmonic of nd : yag laser , 10 ns in pulse , 50 hz ) . the schematic diagram of ntp reactor is presented above ( fig . 1 ) . the reaction dish contained the water solution of eu , y(no3)3 was placed between two electrodes . 1the schematic diagram of ntp reactor the schematic diagram of ntp reactor the stoichiometric amounts of yttrium nitride and europium nitride were dissolved using ultrasounds in 10 ml of deionized water . then the transparent , uniform solution was placed in ntp reactor ( fig . 1 ) . the sample was held in plasma environment at special setup for 2 h. after that solution was divided for 5 samples dried separately at 90 c and sintered for 8 h at temperatures : 425 , 450 , 500 , 600 , 700 , 800 , 850 , and 950 c . the samples with different eu concentrations ( 10 , 5 , 2 , 1 , and 0.5 % ) were also prepared . . 2the block scheme of ntp synthesis process of eu : y2o3 the block scheme of ntp synthesis process of eu : y2o3 the stoichiometric amounts of yttrium nitride and europium nitride were dissolved using ultrasounds in 10 ml of deionized water . then the transparent , uniform solution was placed in ntp reactor ( fig . 1 ) . the sample was held in plasma environment at special setup for 2 h. after that solution was divided for 5 samples dried separately at 90 c and sintered for 8 h at temperatures : 425 , 450 , 500 , 600 , 700 , 800 , 850 , and 950 c . the samples with different eu concentrations ( 10 , 5 , 2 , 1 , and 0.5 % ) were also prepared . 2the block scheme of ntp synthesis process of eu : y2o3 the block scheme of ntp synthesis process of eu : y2o3 the xrd spectra of synthesized materials are presented in figs . 3 , 4 , and 5 . the average grain sizes of the obtained nanopowders were determined using scherrer formula from bordering of diffraction peaks.fig . 3the xrd patterns of eu : y2o3 synthesized in ntp reactor and the reference sample sintered at the same temperaturefig . 4the xrd patterns of eu : y2o3 obtained via non - thermal plasma treatmentfig . 5the xrd patterns of eu : y2o3 nanocrystals with different eu concentrations synthesized by ntp method the xrd patterns of eu : y2o3 synthesized in ntp reactor and the reference sample sintered at the same temperature the xrd patterns of eu : y2o3 obtained via non - thermal plasma treatment the xrd patterns of eu : y2o3 nanocrystals with different eu concentrations synthesized by ntp method the solution was divided into two parts . the first was hold in ntp reactor for 3 h and the second was kept as a reference sample . then the samples were held at temperature 70 c for 24 h and then sintered at 450 and 425 c . it is seen that sample treated by plasma and sintered at 450 c was more phase homogenous . it is seen that with increasing sintering temperature ( figs . 3 , 4 , and 6 ) the average grain size increased . the curve for sample synthesized at 500 c has shown a quite weak crystallization rate . for the samples synthesized at 600 , 700 , and 800 c the size differences were very small14.1 nm at 600 c and 17.8 nm at 800 c . the temperature dependence of average grain size of the obtained nanocrystals at measured temperature range can be approximated as a linear function . it is seen that solution is more temperature sensitive at the range from 800 to 900 c than from 600 to 800 c . the confirmation of this statement is the average grain size of nanocrystals sintered at 850 c , 27.5 nm . 6the effect of sintering temperature on the average grain size of eu : y2o3 nanocrystals synthesized with ntp method the effect of sintering temperature on the average grain size of eu : y2o3 nanocrystals synthesized with ntp method the xrd curves of samples sintered at 900 c with different eu concentrations are presented in fig . it is seen that average grain size calculated using scherrer formula decrease with eu concentration . one can see that the average grain size decreases with concentration of eu ions.fig . 7the eu concentration dependence of average grain size of eu : y2o3 nanocrystals the eu concentration dependence of average grain size of eu : y2o3 nanocrystals such behavior was also observed earlier for other rare earth ions in y2o3 , yag , sno2 , and batio3 nanocrystals . the most probable explanation is mismatching of ionic and atomic radius of europium and yttrium appearing in strong lattice strength influenced by this difference . the tem images of eu : y2o3 nanocrystals sintered at 600 c are presented in fig . 8.fig . 8tem images of eu : y2o3 obtained using non - thermal plasma reactor , sintered at 600 c tem images of eu : y2o3 obtained using non - thermal plasma reactor , sintered at 600 c it is seen that size and shape of the obtained nanocrystals is not uniform . the average grain size estimated from the tem images is similar to the size calculated from scherrer s formula . the luminescence spectra of nanocrystals sintered at 425 and 450 c obtained by using ntp method and the reference one are presented in fig . it is seen that only samples obtained by plasma treatment showed spectra attributed to eu emission at y2o3 host . the photoluminescence of the examined materials is well in correlation with their xrd data and leads to conclusion that fabrication of eu : y2o3 at 450 c and even at 425 c in the most simple way from water solution of nitrides is possible only by using ntp reactor.fig . 9the photoluminescence spectra of eu : y2o3 sintered at 425 and 450 c obtained by ntp method and the reference sample the photoluminescence spectra of eu : y2o3 sintered at 425 and 450 c obtained by ntp method and the reference sample the photoluminescence spectra under exc = 266 nm of eu : y2o3 nanocrystallites with different average grain sizes are presented in fig . 10 . the peaks attributed to the d0 f1 transition are assigned to the magnetic dipole transition and are not affected significantly by the size effect . the second one is electric dipole - allowed transition and is hypersensitive for local crystal field ( morais et al . 10luminescence spectra of eu : y2o3 nanocrystals obtained by ntp method with different average sizes of nanocrystals luminescence spectra of eu : y2o3 nanocrystals obtained by ntp method with different average sizes of nanocrystals the relative intensities of both the transitions\documentclass[12pt]{minimal } \usepackage{amsmath } \usepackage{wasysym } \usepackage{amsfonts } \usepackage{amssymb } \usepackage{amsbsy } \usepackage{mathrsfs } \usepackage{upgreek } \setlength{\oddsidemargin}{-69pt } \begin{document}$$ \beta_{0 \to 1 } = i\left ( { { } ^ { 5 } d_{0 } \to{}^ { 7}f _ { 1 } } \right)/i_{\text{total } } $ $ \end{document}and\documentclass[12pt]{minimal } \usepackage{amsmath } \usepackage{wasysym } \usepackage{amsfonts } \usepackage{amssymb } \usepackage{amsbsy } \usepackage{mathrsfs } \usepackage{upgreek } \setlength{\oddsidemargin}{-69pt } \begin{document}$$ \beta_{0 \to 2 } = i\left ( { { } ^{5 } d_{0 } \to{}^ { 7}f _ { 2 } } \right)/i_{\text{total } } $ $ \end{document}were determined for the samples sintered at different temperatures ( see table 1 ) . here itotal is the total intensity of all luminescent transition bands integrated from 450 to 750 nm.table 1the 01 and 02 ratios in sintering temperature and average grain size functionsintering temperature ( c)500600700800850900average grain size ( nm)7.814.115.017.827.529.4 01 0.1560.1330.1410.1570.1330.159 02 0.5540.2560.2680.3580.2670.412 02/ 01 3.5512.0151.9012.2802.0082.591 the 01 and 02 ratios in sintering temperature and average grain size function a different behavior is observed for eu concentration influence on 02/01 . here , the 02 to 01 ratio increase with concentration ( figs . the observed situation suggests that with increasing of concentration interaction between eu ions and that of crystalline field as in fig . 7 , the size of the obtained nanocrystals decrease with eu concentration . so in single nanograin there is more and more eu ions interacting with local crystalline lattice . however , in the case of 10 % eu : y2o3 where average grain size of nanocrystals , calculated from scherrer s formula is only 31 nm , concentration quenching also plays some role . 11the luminescence spectra of eu : y2o3 nanocrystals with different eu concentrations obtained by ntp methodfig . 12the concentration dependence of 02/ 01 ratio of eu : y2o3 nanocrystals the luminescence spectra of eu : y2o3 nanocrystals with different eu concentrations obtained by ntp method the concentration dependence of 02/ 01 ratio of eu : y2o3 nanocrystals the luminescence studies confirm a good crystallization of eu : y2o3 crystals obtained by ntp method . the eu : y2o3 nanocrystallites were synthesized by new , simple , and efficient method using ntp reactor . it should be emphasized that only the water solutions of yttrium nitride and europium nitride were used as a substrate of the reaction . the average grain size of the obtained nanocrystals increased with sintering temperature and decreased with eu concentration . it was shown that using ntp reactor the synthesis of efficient eu : y2o3 is possible even at 425 c , while reference sample synthesized in the same conditions and even at 450 c was amorphous to a great extent . . the examinations over optimal synthesis conditions and size dependence on luminescence features of different nanocrystals will be a subject of our further studies .

the synthesis of nanosized phosphors by using the non - thermal plasma - driven method is presented . the method allows to control the average grain size of nanocrystals . the synthesis of eu3 + -doped y2o3 nanocrystalline phosphors at water solution of nitrates is described . the average sizes of nanocrystals were controlled by sintering temperature . their structure , morphology , and luminescent properties were investigated .

anti - n - methyl - d - aspartate receptor ( anti - nmdar ) encephalitis is an increasingly recognized etiology of previously unexplained encephalopathy and encephalitis , since its original description in 2007 , . the disease has initially been described in women with an ovarian teratoma but can also be seen in seen in women without an ovarian teratoma , men . the syndrome usually develops with a sequential presentation of symptoms including headache and fever followed by behavioral changes , psychosis , catatonia , decreased level of consciousness , dyskinesias , and autonomic instability . extreme delta brush ( edb ) is a novel electroencephalogram ( eeg ) finding seen in 30.4% of patients with anti - nmdar encephalitis . the presence of this pattern is associated with a more prolonged illness , although the specificity of this pattern is unclear . additionally , the frequency and sensitivity of edb in anti - nmdar encephalitis , its implications for outcome , and whether there is a relationship between this pattern and antibody titers in serum and csf have yet to be determined . we report a 27-year - old woman with no significant past medical history who was brought to the emergency department after becoming odder at home one week after the funeral of her boyfriend . her family reported that she had not been sleeping or eating for a week , and she had been rambling wildly to herself ever since her boyfriend 's funeral . she required chemical sedation in the emergency department as she became violent and hostile towards staff members . she was admitted to the inpatient psychiatry ward for a presumed acute stress reaction with psychosis . she remained uncooperative and was exhibiting delusions that she had to leave because her boyfriend had survived the shooting and was actually waiting for her at home . two days later , she was noted to have sialorrhea and was picking at her clothes and bed sheets . however , she was unresponsive after this seizure and would no longer verbalize or answer questions . the neurology consultant observed that she had minimal responsiveness to voice , had intermittent picking movements at her bed sheets or clothing and was reaching for any instruments used to examine her [ i.e. , stethoscope or reflex hammer ] . she also had a dysconjugate gaze when her eyelids were held open and was hyperreflexic throughout . the initial electroencephalogram ( eeg ) , performed 3 days after presentation , demonstrated frequent electrographic seizures arising independently from the right and left hemispheres . she was given intravenous ( iv ) lorazepam , started on intravenous fosphenytoin , and transferred to the neurological intensive care unit ( icu ) . a lumbar puncture was performed , showing 76 white blood cells / mm with a lymphocytic predominance ( 11 red blood cells / mm , a protein level of 43 mg / dl , and a glucose level of 112 mg / dl ) . the csf was sent for numerous studies including a full paraneoplastic panel , herpes simplex virus pcr , varicella zoster virus pcr , epstein barr virus pcr , cytomegalovirus pcr , arbovirus panel , anti - nmda receptor antibody titer , cytology , and flow cytometry . brain mri with fluid - attenuated inversion recovery ( flair ) images on 7/6/2013 , 4 days after presentation , revealed abnormal high signal in the right medial temporal lobe . on repeat brain mri imaging done two days later on 7/8/2013 , she had hippocampal hyperintensity bilaterally on flair images and enhancement after gadolinium contrast administration ( fig additionally , her continuous eeg monitoring within the first few days began to demonstrate frontally maximal high - voltage beta activity superimposed on frontally maximal delta waves ( fig . 2 ) . this pattern of extreme delta brush had been described as highly suggestive of anti - nmdar encephalitis . given suspicion for an autoimmune - mediated process causing her symptoms , 1000 mg of methylprednisolone was started on 7/9/2013 , 7 days after presentation . in addition , she was then started on plasmapheresis once the steroid course was completed . her csf result was positive for anti - nmda receptor antibodies , and her diagnosis was therefore confirmed as anti - nmda receptor encephalitis . numerous studies including ct torso , pelvic and vaginal ultrasound , pelvis mri , and a pet scan either showed no evidence of malignancy or were limited by body habitus . a pelvic ultrasound was repeated given persistent elevated concern for an occult malignancy and revealed a right ovarian mass that was concerning for an underlying tumor . on 8/14/2013 , 43 days after presentation , she underwent laparoscopic right salpingo - oophorectomy . surgical pathology report was consistent with a mature cystic teratoma , which was ultimately believed to be the etiology of her immune - mediated encephalitis . unfortunately , there was no evident response to treatment . despite completing 15 rounds of plasmapheresis , high - dose steroids , cyclophosphamide , rituximab , and ketamine , her oral facial and limb dyskinesias continued to be pronounced , and she continued to have large fluctuations in temperature , blood pressure , and heart rate . her anti - nmdar antibody remains positive ( last tested on 11/11/2013 , 132 days after presentation ) . additionally , follow - up eeg performed on 10/31/2013 , 121 days after presentation , continued to show pronounced extreme delta brush ( fig . 3 ) . we report a 17.5-week follow - up of a young woman with anti - n - methyl - d - aspartate receptor ( anti - nmdar ) encephalitis associated with an ovarian teratoma . the diagnosis was confirmed by persistence of a positive serum anti - nmdar antibody and the continued presence of extreme delta brush ( edb ) on continuous eeg . extreme delta brush is a novel eeg finding seen in many patients with anti - nmdar encephalitis . in this particular patient , although specificity is uncertain , early diagnostic evaluation for malignancy should be pursued on the basis of clinical findings and edb before the titers return . because edb is associated with a more prolonged illness , whether the persistence of this pattern has further implications for outcome is unclear . whether there is a relationship between this edb pattern and antibody titers in serum and csf has yet to be determined . additionally , whether there is a relationship between persistence of the anti - nmdar antibody and continued edb is also unclear . however , the persistence of the finding has not been adequately correlated with outcomes or prognosis and requires further investigation .

since its original description in 2007 , anti - n - methyl - d - aspartate receptor ( anti - nmdar ) encephalitis associated with an ovarian teratoma is an increasingly recognized etiology of previously unexplained encephalopathy and encephalitis . extreme delta brush ( edb ) is a novel electroencephalogram ( eeg ) finding seen in many patients with anti - nmdar encephalitis . the presence of this pattern is associated with a more prolonged illness , although the specificity of this pattern is unclear . additionally , the frequency and sensitivity of edb in anti - nmdar encephalitis and its implications for outcome have yet to be determined . we report a patient with early evidence of extreme delta brush and persistence of this pattern 17.5 weeks later with little clinical improvement .

when slow gradual occlusion happens as like in perihilar cholangiocarcinoma , such dilatation becomes insidious thus showing diffuse dilatation of the involved intrahepatic bile ducts . in contrast , if rapid gradual occlusion is associated with friable liver parenchyma such as rapidly regenerated remnant livers or partial liver grafts following living donor liver transplantation , such pressure increase in the intrahepatic bile duct can induce intrahepatic biloma formation.1 - 4 in any situation , spontaneous rupture of the intrahepatic duct or biloma has not been reported yet in literature . we herein present a case of spontaneous rupture of intrahepatic bile duct in a patient with perihilar cholangiocarcinoma following portal vein embolization , which were successfully treated by curative resection . a 60-year - old male patient was referred to our institution under the diagnosis of perihilar cholangiocarcinoma . computed tomography ( ct ) findings were compatible to those of hilar cholangiocarcinoma bismuth - corlette type iiia with encasement of the right hepatic artery ( fig . a percutaneous transhepatic biliary drainage ( ptbd ) tube was inserted into the right hepatic duct , and crossed over the hilar stenotic portion and then passed into the ampulla of vater for probably simultaneous internal drainage . since we were not accustomed to such placement of ptbd tube and total bilirubin level decreased gradually like in the usual perihilar cholangiocarcinoma cases , we did not perform any other procedure for biliary drainage . in order to induce regeneration of the future remnant left liver two days after this procedure , the patient suffered from paralytic ileus with marked abdominal distension ( fig . emergency ct scan revealed that marked fluid collection around the liver and whole abdomen , thus percutaneous drainage was performed with insertion of a pigtail catheter over the left liver . the pigtail drainage output was bilious in nature , thus leading the diagnosis of intrahepatic bile duct rupture . follow - up ct scan showed residual fluid collection in the other area of the abdomen , thus another pigtail catheter was inserted into the pelvis . at this time , we recognized that the underlying cause of intrahepatic bile duct rupture was ineffective drainage of the left hepatic duct with overproduction of bile after right portal vein embolization . 4 ) . to enhance the safety of right hepatectomy , we performed additional right hepatic vein embolization to facilitate left liver regeneration ( fig . , we found that the ruptured area was the diaphragmatic side of the segment ii because the superficial liver parenchyma at that area was definitely torn out . after confirmation of respectability with limited dissection of the hepatoduodenal ligament , we carried out routine surgical procedures for right hepatectomy , caudate lobectomy and bile duct resection and reconstruction . pathological reports showed that the tumor was a 2.1 cm - sized cholangiocarcinoma with extension to perifibromuscular connective tissue and positive lymphovascular invasion ( fig . the underlying cause of intrahepatic bile duct rupture in this case was ineffective drainage of the left hepatic duct superimposed to overproduction of bile from the left liver following right portal vein embolization . to our knowledge , spontaneous rupture of the intrahepatic duct or biloma at any cause has not been reported yet in literature . in this case , there was no possibility of iatrogenic intrahepatic duct injury because right portal vein embolization was performed through an ipsilateral approach , thus making no touch to the left liver . for preoperative evaluation of bile duct involvement in perihilar cholangiocarcinoma , frequent serial surveillance of all dilated intrahepatic ducts is very beneficial for effective biliary decompression . we strongly suggest performing dynamic liver ct scan a few days before surgery to finally evaluate the liver status . biliary obstruction due to malignancies of the hepatobiliary system often requires biliary drainage through percutaneous or endoscopic approach . ptbd has been widely used for a long time , but has various drawbacks including procedure - related complications and tumor spread along the ptbd tract , leading to the adoption of endoscopic biliary drainage as the primary method.1 - 5 endoscopic biliary drainage including endoscopic naso - biliary drainage for external drainage and endoscopic retrograde biliary drainage for internal drainage has been shown effective for biliary decompression of distal bile duct cancer , reducing the need for ptbd . in patients with perihilar cholangiocarcinoma , however , endoscopic naso - biliary drainage is often infeasible or ineffective due to the complexity of the biliary obstruction patterns . thus , ptbd is still frequently performed in patients with perihilar cholangiocarcinoma , with complementary application of endoscopic naso - biliary drainage in patients with less advanced cancers.6,7 portal vein embolization induces shrinkage of the embolized lobe and compensatory enlargement of the non - embolized lobe , but it does not always induce sufficient liver regeneration . there was no effective method to accelerate liver regeneration in addition to portal vein embolization yet . the early experience of first 12 cases on the effect of ipsilateral hepatic vein embolization performed after portal vein embolization was presented before.8 in a total of 30 cases of sequential portal vein embolization - ipsilateral hepatic vein embolization in our recent series , the proportions of future liver remnant volume to total liver volume increased further after hepatic vein embolization without occurrence of any procedure - related complications . we are sure that preoperative sequential application of sequential portal vein embolization - ipsilateral hepatic vein embolization is safe and effective in facilitating contralateral liver regeneration by inducing more severe liver damage than portal vein embolization alone.8 - 10 this is the first report of a case of spontaneous rupture of intrahepatic bile duct following portal vein embolization in a patient with perihilar cholangiocarcinoma .

we herein present a case of spontaneous rupture of intrahepatic bile duct in a patient with perihilar cholangiocarcinoma , which were successfully treated by curative resection . a 60-year - old male patient with perihilar cholangiocarcinoma was decompressed with single percutaneous transhepatic biliary drainage . two days after right portal vein embolization , the patient suffered from paralytic ileus with marked abdominal distension . imaging study revealed that marked fluid collection around the liver and whole abdomen , suggesting intrahepatic bile duct rupture . with abdominal drainage and biliary decompression for 2 weeks , the biliary rupture was controlled . to enhance the safety of right hepatectomy , additional right hepatic vein embolization was performed . the patient underwent routine surgical procedures for right hepatectomy , caudate lobectomy and bile duct resection , and recovered uneventfully and discharged 18 days after surgery . this is the first report of a case of spontaneous rupture of intrahepatic bile duct in a patient with perihilar cholangiocarcinoma .

in october 2011 , a 39-year - old woman presented a painless mass in her left breast for 3 months . there were no accompanying symptoms such as nipple retraction , dimpling , or palpable axillary lymph nodes . physical examination revealed a 2 cm 2 cm , elastic , firm , ill - defined suspicious mass in the upper outer quadrant of her left breast . on the mammography , the mass appeared round with indistinct margins with lots of punctates and scattered calcifications along the duct ( figure 1a ) . a , mammography reveals a round mass with obscure margins and lots of punctates and scattered calcifications along the duct . b and c , ultrasound scan shows two solid and low heterogeneous echoes in the left breast . one is in the 3 o'clock position , 65 mm away from the nipple ( b ) ; the other is also in the 3 o'clock position , 35 mm away from the nipple ( c ) . additionally , an ultrasound scan revealed two solid and low heterogeneous echoes in the left breast : one was in the 3 o'clock position , 35 mm away from the nipple ( figure 1b ) ; the other was also in the 3 o'clock position , 65 mm away from the nipple ( figure 1c ) . both were poorly defined with irregular borders . however , the levels of serum tumor markers , including carcino - embryonic antigen ( cea ) , carbohydrate antigen 125 ( ca125 ) , ca15 - 3 , and ca19 - 9 were all within normal limits . an intraoperative biopsy confirmed the pathologic diagnosis of scc with the component of ductal carcinoma in situ ( dcis ) . as a result , she underwent modified radical mastectomy with axillary lymph node dissection . microscopically , the mass ( in the 3 o'clock position , 35 mm away from the nipple ) was about 0.8 cm 0.5 cm 0.5 cm , which was diagnosed histologically as an intermediate grade dcis , whereas the second mass ( in the 3 o'clock position , 65 mm away from the nipple ) was about 1.4 cm 1.2 cm 0.6 cm and was comprised of intermediate grade dcis ( 30% ) and scc ( 70% ) . histological examination showed that the tumor was composed of small round or oval cells with a high nucleocytoplasmic ratio , small hyperchromatic nuclei , inconspicuous nucleoli , and scant cytoplasm , which were arranged diffusely and patchily . immunohistochemically , tumor cells of the dcis component were positive for estrogen receptor ( er ) , progesterone receptor ( pr ) , and human epidermal growth factor receptor 2 ( her2 ) . however , the tumor cells of the scc component were negative for these markers , whereas the ki67 proliferation index ( percentage of ki67-positive cancer nuclei ) was 70% . furthermore , the scc tumor cells were highly positive for neuroendocrine differentiation markers including synaptophysin ( figure 2b ) , neuron specific enolase ( nse ) ( figure 2c ) , thyroid transcription factor-1 ( ttf1 ) ( figure 2d ) , and cd56 ( figure 2e ) , but they were negative for chromogranin a ( cga ) ( figure 2f ) . histological examination also demonstrated 1 positive lymph node out of 13 level i axillary lymph nodes . a , the small cell carcinoma component ( left ) is comprised of small round or oval cells with hyperchromatic nuclei , scant cytoplasm , and inconspicuous nucleoli , accompanied with a ductal carcinoma in situ component ( right ) ( he 200 ) . the small cell carcinoma component ( left ) is positive for synaptophysin ( b ) , neuron specific enolase ( c ) , thyroid transcription factor-1 ( d ) , and cd56 ( e ) and is negative for chromogranin a ( f ) ; whereas the ductal carcinoma in situ component ( right ) is negative for all the above markers ( ihc 200 ) . therefore , a search for a non - mammary primary site was carried out , especially focusing on pathologic changes in the lungs . the result of computed tomography ( ct ) scans of the neck , chest , and upper abdomen were all within normal limits , and bone scintigraphy was negative for metastatic disease . as a result , we concluded that the breast was the primary site , and primary scc of the breast was diagnosed . the patient was treated with six cycles of docetaxel ( 75 mg / m ) and carboplatin ( 350 mg / m ) in combination once every three weeks . after the initial treatment , the patient was clinically monitored for disease relapse and metastasis . small cell neuroendocrine carcinoma has been described in many extra - pulmonary sites , including the breast , larynx , gastrointestinal tract , prostate , bladder , ovary , and cervix , . in particular , primary scc of the breast is considerably rare . to our knowledge , 56 cases have been reported in the literature,. in summarizing the clinicopathologic characteristics of these cases , most of them are found in women ; only two male cases have been reported , . the median age of the patients at presentation was 52 years ( range , 29 to 81 years ) . tumor size ranged from 1 to 18 cm ( mean , 4.63 cm ) , and about 62.8% of the tumors ( 2 to 5 cm in size ) were in t2 stage according to the national comprehensive cancer network ( nccn ) guidelines . primary scc of the breast can be diagnosed if there is no evidence for an extra - mammary primary site or if an in situ component can be demonstrated histopathologically within the breast . it is important that the dcis component is truly a precursor lesion of scc and supports a primary breast origin . the presence of an in situ component is useful , though not indispensable , toward the diagnosis of primary breast tumors . we also reviewed previous immunohistochemical reports,. the tumor cells from approximately 28.8% ( 15/52 ) of reported patients were positive for either er or pr . however , her2 overexpression has never been reported in these cases . in general , the positive rates of er , pr , and her2 were about 60%70% , 50%60% , and 20%30% , respectively , displaying a common phenotype of invasive ductal carcinoma , . moreover , positive neuroendocrine markers could provide strong support for diagnosis . the positive rates of nse and synaptophysin were 88.2% ( 45/51 ) and 63.8% ( 30/47 ) , respectively , and some of the tumor cells were positive for cd56 , ttf1 , cga , and other markers . this type of breast carcinoma is rare and has generally been considered to be extremely aggressive . as a result , no standard treatment for this disease exists , . the most effective option seems to be modified radical mastectomy with axillary lymph node dissection followed by adjuvant chemotherapy . considering that the biological characteristics of this type of breast carcinoma are similar to scc of the lung , effective drugs for scc , such as platinum compounds and etoposide , were selected to treat these patients ; drugs for common types of breast cancer were not selected . paclitaxel has been found safe and effective as first - line therapy for small cell lung carcinoma . in addition , paclitaxel - containing regimens have also been used for patients with breast cancer as a standard adjuvant therapy . in the case of scc with a dcis component , we prefer a docetaxel and carboplatin combination rather than other ordinary regimens such as cyclophosphamide , epirubicin , and 5-fluorouracil ( cef ) . individual treatment strategy , including chemotherapy , radiotherapy , and endocrine therapy alone or in combination , should be determined according to patient 's age , tumor size , axillary lymph node status , and molecular phenotype . the prognosis for this type of tumor is generally believed to be as poor as its pulmonary counterparts . however , previous reports show that the prognosis can be better if such tumors are detected at an earlier stage . according to previous reports, , the mean follow - up time was 21 months ( range , 3 to 60 months ) , the metastasis or relapse rate was 35.7% ( 20/56 ) , and the mortality was 19.6% ( 11/56 ) . the most common sites of metastasis were the liver , brain , bone , lungs , and lymph nodes . the treatment of disease relapse , however , remains poorly characterized . as for our 39-year - old patient , tumor cells of the scc component were negative for er , pr , and her2 . in addition , the high ki67 index and the presence of metastases in 4 axillary lymph nodes may result in a high risk of disease relapse and metastasis . thus , after her systemic and individual treatments , a rigorous clinical monitoring of disease relapse and metastasis is necessary . in summary , primary scc of the breast is a new challenge . due to the rarity of cases , further studies with more cases will enhance our understanding of the clinicopathologic characteristics of this tumor and may result in the development of new therapeutic modalities , thus improving the outcome of these patients .

primary small cell carcinoma ( scc ) of the breast , an exceedingly rare and aggressive tumor , is often characterized by rapid progression and poor prognosis . we report a case of primary scc of the breast that was diagnosed through pathologic and immunohistochemical examinations . computed tomography ( ct ) scans failed to reveal a non - mammary primary site . due to the scant number of relevant case summaries , this type of tumor is proved to be a diagnostic and therapeutic challenge . therefore , we also reviewed relevant literature to share expertise in diagnosis , clinicopathologic characteristics , treatment , and prognosis of this type of tumor . future studies with more cases are required to define more appropriate treatment indications for this disease .

paraquat ( 1,1'-dimethyl-4 , 4'-bipyridium dichloride , pq ) is one of the most widely used herbicides in the world . in humans , intentional or accidental ingestion of pq is frequently fatal , resulting from significant lung injury ( 1 ) . over the past 30 yr , several methods for modifying the toxicity of pq have been investigated including prevention of absorption from the gastrointestinal tract ( 2 , 3 ) , removal from the bloodstream ( 4 , 5 ) , prevention of accumulation in the lungs ( 6 , 7 ) , scavenging oxygen free radicals ( 8 , 9 ) , and prevention of lung fibrosis ( 10 , 11 ) . unfortunately , most of these methods have not been effective ; and the clinical outcome is determined by the degree of exposure to pq . pq mainly accumulates in the lung where it is retained even when the blood levels start to decrease . subsequent redox cycling and the generation of reactive oxygen species ( ros ) trigger the lung injury ( 12 , 13 ) . this is the reason why intentional or accidental pq ingestion frequently causes death by respiratory failure ( 12 ) . there are many methods available for evaluation of the severity of lung injury in acute pq intoxication , such as arterial blood gas analysis ( abga ) , high - resolution computed tomography ( hrct ) of the lung ( 14 ) . also there are some markers for alveolar destruction in acute pq intoxication , such as ethane in exhaled breath ( 15 ) , and plasma surfactant levels ( 16 ) . we previously reported that hrct of the lung obtained 7 days after pq ingestion was the best way to evaluate the fully developed acute pq lung injury ( 14 ) . the initial pathology of the lung is alveolitis , which develops into ground glass opacities ( ggos ) in hrct . the mortality rate is strongly associated with the plasma pq levels as well as the amount of pq ingested ( 17 - 19 ) . considering the significant association of the pq level with clinical outcome and the fact that respiratory failure is the main cause of death , the extent of the lung injury might be related to the plasma pq levels . nevertheless , the correlation of the extent of the lung injury with plasma pq levels and clinical outcome is unknown . to determine the association of the development of ggos with plasma pq levels and clinical outcome , we analyzed the results of lung hrct scans obtained in patients with acute pq intoxication and attempted to determine the factors that distinguished the survivors from those that did not survive . this study was approved by ethics committee of soonchunhyang university cheonan hospital and received a written consent from the patients and/or their family . from january to november 2007 , 250 patients ( 143 males and 107 females ) with acute pq intoxication were admitted to the institute of pesticide poisoning ( ipp ) , soonchunhyang university cheonan hospital . of 250 patients 119 ( 68 males and 51 females ) were enrolled in this study . the inclusion criteria were patients who swallowed pq and had acute pq intoxication confirmed at the ipp with the dithionite urine test and/or plasma pq levels . hrct was not done in 131 patients who were dead or hopelessly discharged within 7 days after pq ingestion . as we described in a previous report ( 20 ) , the survivor was defined as the patient who remained alive longer than 4 weeks after discharge . the mean age of the subjects was 43.312.2 yr . the ingestion amount ( mean ; 25.023.9 ml of 23% pq ; in korea , most pq products are a 23.0% solution ) was determined by the reported mouthfuls ingested ( one mouthful ; 20 ml ) . the plasma pq level of the subjects in the emergency room was 0.571.72 g / ml retrospectively . the time interval between pq ingestion and arrival to the ipp was 21.230.3 hr . all hrct scans were obtained 7 days after pq poisoning using an eight - detector ( lightspeed ultra , ge healthcare ) or 64-detector ( lightspeed vct , ge healthcare , u.s.a . ) row scanners . the scanning parameters were 120 kvp , 200 or 300 ma , beam width 10 or 20 mm , and a pitch of 1.675 or 1.375 . the 1.25 mm thin - section computed tomography ( ct ) scans with 5 mm intervals were acquired using retrospective reconstruction of raw data with a lung algorithm . hrct images were available at a picture archiving and communication systems ( pacs ) with appropriate lung ( window width , 1500 , window level , -650 ) window settings on the monitors ( four monitors , 2,0482,560 matrix , 8-bit viewable gray , 500 cd / m ) . the areas of ggos were measured at five levels ( at the levels of the top of aortic arch , aortopulmonary ( ap ) window , left upper lobe ( lul ) bronchus , right inferior pulmonary vein , and the top of left diaphragm ) using the area measurement tool of the pacs . to calculate the extent of the lung injury , the sum of the area of ggos at the five levels were divided by the sum of the areas of the total lung at the respective levels . sometimes , it is difficult to differentiate ggos from consolidation . in this study , if the area of focal consolidation is located within the boundary of ggo , it was regarded as area of ggos . if the area of consolidation was located outside the area of ggo , this area was not included in the area of ggo . data are presented as meansd and range of distribution when the distribution of data was unusually wide . comparison of the parameters was performed with the t - test ; but the mann - whitney test was applied for the time lag after pq ingestion , estimated ingestion amount ( ml ) , area with ggos on hrct ( % ) , aspartate minotransferase ( ast ) , alanine aminotransferase ( alt ) , amylase , and lipase because of the unusually wide distribution of the raw data . all hrct scans were obtained 7 days after pq poisoning using an eight - detector ( lightspeed ultra , ge healthcare ) or 64-detector ( lightspeed vct , ge healthcare , u.s.a . ) row scanners . the scanning parameters were 120 kvp , 200 or 300 ma , beam width 10 or 20 mm , and a pitch of 1.675 or 1.375 . the 1.25 mm thin - section computed tomography ( ct ) scans with 5 mm intervals were acquired using retrospective reconstruction of raw data with a lung algorithm . hrct images were available at a picture archiving and communication systems ( pacs ) with appropriate lung ( window width , 1500 , window level , -650 ) window settings on the monitors ( four monitors , 2,0482,560 matrix , 8-bit viewable gray , 500 cd / m ) . the areas of ggos were measured at five levels ( at the levels of the top of aortic arch , aortopulmonary ( ap ) window , left upper lobe ( lul ) bronchus , right inferior pulmonary vein , and the top of left diaphragm ) using the area measurement tool of the pacs . to calculate the extent of the lung injury , the sum of the area of ggos at the five levels were divided by the sum of the areas of the total lung at the respective levels . sometimes , it is difficult to differentiate ggos from consolidation . in this study , if the area of focal consolidation is located within the boundary of ggo , it was regarded as area of ggos . if the area of consolidation was located outside the area of ggo , this area was not included in the area of ggo . data are presented as meansd and range of distribution when the distribution of data was unusually wide . comparison of the parameters was performed with the t - test ; but the mann - whitney test was applied for the time lag after pq ingestion , estimated ingestion amount ( ml ) , area with ggos on hrct ( % ) , aspartate minotransferase ( ast ) , alanine aminotransferase ( alt ) , amylase , and lipase because of the unusually wide distribution of the raw data . there was no difference between the survivors and those who did not survive by age ( 42.412.3 yr vs. 44.6 11.0 yr , p=0.488 ) or gender ( male / female : 58/44 vs. 10/7 , p=0.880 ) . the wbc count was higher in those that did not survive than those survived ( 17,336.55,283.6 l vs. 10,942.6 4,452.2 l , p<0.001 , table 2 ) . the estimated ingestion amount of pq was lower in the survivors than in the dead ( 19.411.3 ml vs. 59.244.7 ml , p<0.001 ) . between the survivors and those that did not survive there was no significant difference in the interval between pq ingestion and arrival to the emergency room , ( 22.131.9 hr vs. 16.2 18.2 hr , p=0.45 ) . however , the plasma pq levels were significantly higher in those that did not survive than the survivors ( 2.64.0 g / ml vs. 0.20.4 g / ml , p=0.02 ) . the area of the lung with ggos was 2.036.44% in the survivors and 73.029.93 in those that did not survive ( p<0.001 ) . the area of ggos was zero in 40 out of 102 survivors and it was larger than 80% in 9 out of 17 patients that did not survive . eight subjects ( 3 survivors and 5 non - survivors ) had between 20 - 40% ggos . plasma pq levels are known to be an excellent prognostic indicator for patient outcome ( 17 - 19 ) . however , at the bedside , it is difficult to predict survivors even when the pq levels are known . recently , we published an analysis of our clinical observations , which showed an association between plasma pq levels and clinical outcome in 375 patients with acute pq intoxication ( 20 ) . based on the information from the plasma pq levels it was hard to predict who would survive because many patients died even at low pq levels . therefore , better predictive measures are needed for patients presenting with acute pq intoxication . because lung injury is the main cause of death after acute pq intoxication the initial pathology of pq intoxication is an alveolitis , which is later shown as ggos in hrct . in diagnosing the lung injury caused by pq we evaluated the severity of the lung injury by measuring the extent of involved lung . the results of this study showed that there were no deaths when the area of ggos was smaller than 20% of the total lung volume . in addition , there were no survivors when the area of ggos was larger than 40% of the total lung volume . when 20% and 40% of the total lung volume was affected , some patients died and others survived . for those patients who died within 7 days before they took the hrct , we presume that ggo might have developed across their entire lungs . there was no such ggo area in the 40 cases out of 119 survivors , more than 80% of such inflicted area in the 9 cases out of the 17 non - survivors . eight cases were transitional between 20 - 40% of ggo trace in the lung . in these transitional cases , given the fact that the minimum fatal pq level can be very low in practice ( fig . 2 ) , the area of ggo in the lung is an additional useful predictor for the survival , especially when the pq level is low .

even though plasma paraquat ( pq ) levels have known to be an informative predictor , many patients succumb at low pq levels in acute pq intoxication . this study was designed to see whether the high resolution computerized tomography ( hrct ) of the lungs would be a predictive measure in acute pq intoxication . hrct of the lungs was obtained from 119 patients with acute pq intoxication on 7 days after pq ingestion . the areas with ground glass opacities ( ggos ) were evaluated at five levels with the area measurement tool of the picture archiving and communication systems . among 119 patients , 102 survived and 17 died . the plasma pq levels were significantly higher in the non - survivors than in the survivors ( 2.64.0 g / ml vs. 0.20.4 g / ml , p=0.02 ) . the area with ggos was 2.06.4% in the survivors and 73.0 29.9% in the non - survivors ( p<0.001 ) . no patients survived when the area with ggos was more than 40% but all of the patients survived when the area affected by ggos was less than 20% . in conclusion , the area of ggos is a useful predictor of survival in acute pq intoxication , especially in patients with low plasma pq levels .

it can be argued that medical ethics is a collection of behaviors and if it is taught through traditional methods , it may not change the students attitudes and practice satisfaction . therefore , departments of medical ethics have showed an interest in using student - centered methods . student - centered approaches to learning enable students to distinguish ethical dilemmas , solve problems and make proper decisions ( 24 ) . it is known that problem based learning ( pbl ) is a desirable method for teaching and learning in medical ethics . it is desirable , because the nature of ethical enquiry is highly compatible with the learning processes which characterize pbl ( 5 ) . learning ethics in small groups is widely accepted and is practiced in some universities ( 1 , 69 ) . on the other hand , tysinger et al . suggested a combined lecture / small group discussion ( sgd ) in teaching ethics because it offers the advantage of systematically covering the chosen breadth of theory and the chosen range of common moral problems in medicine ( 10 ) . we did not find studies that compared pbl and sgd methods , but we believe that problem based learning is more complex and time consuming than sgd . in addition problem based medical ethics was a part of the curriculum for medical students in traditional iranian medicine in medieval times , and great iranian physicians have paid special attention to ethics in their practice , teaching and manuscripts . when the faculty of medicine was first established in tehran university in 1934 , teaching medical ethics comprised a part of medical students education courses ( 11 ) . in recent years , there has been an increased emphasis on classic ethics education and nowadays ethics is taught in all medical universities of iran ( 12 ) . in qom university of medical sciences , all medical universities in iran are instructed on the components of the ethics curriculum by the ministry of health and medical education . the contents of the course are planned for 16 sessions as seen in table 1 . up to the present time , ethics has been taught using the lecture method in qom university of medical sciences . it is clear that the traditional systems for teaching ethics are no longer sufficient to meet the needs of practitioners and societies and new methods , particularly those emphasizing active learning , individual participation , group interactions and a process - based approach should be developed and implemented ( 13 ) . we know that pbl and sgd methods are very useful methods in ethics education ( 1 , 57 ) ; however , it is unknown if they have different effects on learning or not . in the first semester of the academic year 20102011 , twenty students were introduced for ethics course . the students were randomly assigned into two groups using a table of random numbers ( 6 females and 4 males in each group ) . since pbl and sgd were new to most students and some faculties , both students and facilitators received separate course orientations to meet their particular needs . in the student orientation , the course director gave an overview of the course , explained the two teaching methods and suggested references . in this study , nine members of the medical ethics department ( the first nine authors ) acted as facilitators . facilitators orientation was provided using a teaching guideline . in the pbl group , students received scenarios one week before the relative session . in the week between the sessions , students were required to search and study the learning issues they identified in the cases , organize and summarize the key information in their learning issues to present to the group , and try to resolve the cases ethical dilemmas . during the sessions , the students presented the learning issues they had searched and discussed and resolved the case problems under supervision of facilitators . in the sgd group , students only had the sessions headings . facilitators stated the problems and questions about the heading in each session , and then the students tried to solve the problems and answer the questions by brainstorming . there was one facilitator presented at each session whose main function was to help the discussion and enable the students to think about the problems and solve them rather than act as a source of knowledge . validity of these questions was confirmed by the medical ethics department of qom university of medical sciences . a course evaluation sheet was used at the end of the course to obtain the students views about the advantages and disadvantages of each teaching method ( using two open - ended questions ) , their satisfaction ( using four point likert scale questions : 1 = very low , 2 = relatively low , 3 = relatively high , 4 = very high ) , their interest to attend the sessions , and their opinion regarding the effect of teaching ethics on students behavior . pbl students were asked if they had studied the scenarios and if they said yes , they were asked how many sessions they had searched . validity of the sheet was confirmed by the medical ethics department of qom university of medical sciences . the reliability of questionnaires based on the chronbach s alpha coefficient of internal consistency was 0.66 . distribution and collection of the sheets was done by a person outside the research team . the spss statistical package version 17 was used to test whether there were any statistically significant differences between the pbl and the sgd students in the mean open - ended question scores and their satisfaction rate . both independent sample t - test and mean and standard deviation of scores in pbl and sgd groups were 16.04 1.84 and 15.48 2.01 respectively . in order to detect the difference between the learning outcome in pbl and sgd methods , we compared the mean of students scores in both groups . there was no significant difference in learning outcome between the pbl and the sgd students in the mean scores as assessed by open - ended questions . nineteen out of 20 students completed the course evaluation sheet ( response rate = 95% ) . the results from questions showed no significant difference between the two groups ( table 2 ) . some of the student comments about the advantages and disadvantages of teaching methods in the two groups were listed in table 3 . all of the students in the pbl group stated that they studied the scenarios in the week between sessions . the mean ( sd ) of sessions that they studied was 10.33 4.3 ranging from 4 to 16 sessions . mean and standard deviation of scores in pbl and sgd groups were 16.04 1.84 and 15.48 2.01 respectively . in order to detect the difference between the learning outcome in pbl and sgd methods , we compared the mean of students scores in both groups . there was no significant difference in learning outcome between the pbl and the sgd students in the mean scores as assessed by open - ended questions . nineteen out of 20 students completed the course evaluation sheet ( response rate = 95% ) . the results from questions showed no significant difference between the two groups ( table 2 ) . some of the student comments about the advantages and disadvantages of teaching methods in the two groups were listed in table 3 . all of the students in the pbl group stated that they studied the scenarios in the week between sessions . the mean ( sd ) of sessions that they studied was 10.33 4.3 ranging from 4 to 16 sessions . despite of efforts for promotion of teaching medical ethics in iran , the method of teaching is still lecture - based in most medical schools . a suitable teaching ethics program , however , would be based on using new methods especially those emphasizing active learning and student participation . two key features related to the teaching of medical ethics have been widely recognized as beneficial ; the first feature is actively involving students in the learning process , and the second is assessing how students apply their knowledge of ethical principles in simulated and actual situations ( 10 ) . the purpose of this study was to compare pbl and sgd for teaching medical ethics through applying these methods to two separate groups of students . although the results did not show any significant difference between the learning outcomes in either group , the mean score of pbl students was higher than sgd students . one possible explanation for the findings may be related to the nature of ethical concepts , as most ethical problems could be solved by unassisted thinking . however , it should be noted that although the pbl group students stated that they searched and studied between sessions , we can not be certain that they spent enough time on problem solving and did not use their peers search results . as the students stated , their workload did not permit them to spend enough time on search and consequently there was no significant difference between the two methods . as mentioned in the introduction , we did not find studies comparing pbl and sgd methods . nevertheless , the results are in agreement with those of goodyear s study that found no significant difference in learning outcome between the traditional and pbl courses , but the pbl course was well appreciated by his study population ( 14 ) . likewise , fesharaki et al . did not report any significant difference between scores of students in lecture and pbl groups ( 15 ) . moreover , salimi et al . showed that lecture and sgd methods had similar effects on drug calculation skills ( 16 ) . these studies had compared pbl and sgd methods with the lecture method and did not find any significant difference either . hence , in 4 out of 5 questions the mean score of pbl subjects was higher than the other group even though this difference was not statistically significant . johnston and haughton reported that their students certainly preferred small group teaching as a way of promoting debate and discussion ( 17 ) . thus , tan et al . found that 35 years after participation in the pbl method , 68% of students perceived pbl as helpful in collaboration with colleagues , working in small groups , taking responsibility for contribution to the group and accountability to other group members ( 18 ) . in another study about students satisfaction after sgd in a medical ethics education program , students reported greater satisfaction with self - case , presentation experience , in - class discussion , and instructor s comments , but less satisfaction with self - study and before class and post class discussion . reported overall satisfaction score was 3.8 0.9 ( mean sd ) ( 19 ) . we did not assess the students satisfaction with specific components of an sgd but the overall satisfaction mean score in both studies were similar . also fawzi reported that 56% of the medical students in his study preferred daily confusing ethical issues problem solving , 24% case and solution and 13.3% small group study . only 6.7% of them chose the lecture - based method ( 4 , 20 ) . the usefulness of pbl and sgd methods is obvious since students actively participate in learning , although there are disadvantages to each of these methods . in pbl the need for providing the necessary resources to students has to be considered . in our study , for instance , we had to provide ethics references such as books for students as our library did not have sufficient books . on the other hand , one important disadvantage of sdg is the need for longer sessions , since the students are generally not familiar with the topics prior to each session . it is noteworthy that some universities have added other methods such as monthly ethics grand rounds and mandatory ethics seminars to pbl and sgd methods ( 1 , 21 ) . interactive lectures and small research projects in a hospital or clinic ( 2 ) are performed as well ( 22 ) . ward rounds ( 7 , 23 ) and role - playing ( 24 ) may likewise be used along with these methods ( 3 ) . there were some limitations to our study , the most important one being the small sample size . another limitation pertained to examining the effects of the pbl and sgd methods on areas that we did not cover in this study , for instance clinical practice . furthermore , the students ethical knowledge was assessed only a short time after the course , and therefore the effectiveness of each method over a longer time span could not be verified . the reliability of the open - ended questions used for the purpose of assessment was yet another limitation . in view of the most important limitation of this study , namely the small sample size , and taking into account the students comments on the advantages and disadvantages of each method , we suggest pbl rather than sgd for teaching ethics . considering the process of the pbl method and unavailability of the required resources , however , this method may not be suited to ethics education under the present circumstances .

lecture is the most common teaching method used in ethics education , while problem - based learning ( pbl ) and small group discussion ( sgd ) have been introduced as more useful methods . this study compared these methods in teaching medical ethics.twenty students ( 12 female and 8 male ) were randomly assigned into two groups . the pbl method was used in one group , and the other group was taught using the sgd method . twenty - five open - ended questions were used for assessment and at the end of the course , a course evaluation sheet was used to obtain the students views about the advantages and disadvantages of each teaching method , their level of satisfaction with the course , their interest in attending the sessions , and their opinions regarding the effect of teaching ethics on students behaviors . the mean score in the pbl group ( 16.04 1.84 ) was higher than the sgd group ( 15.48 2.01 ) . the satisfaction rates in the two groups were 3.00 0.47 and 2.78 0.83 respectively . these differences were not statistically significant.since the mean score and satisfaction rate in the pbl group were higher than the sgd group , the pbl method is recommended for ethics education whenever possible .

the human pancreatic adenocarcinoma bxpc-3 ( atcc crl-1687 ) epithelial cell line was grown in rpmi-1640 ( sigma - aldrich , st louis , mo , usa ) supplemented with 10% fetal bovine serum , 1% penicillin / streptomycin and 0.002 insulin transferrin selenium ( life technologies , carlsbad , ca , usa ) cells were propagated at 37 c in a humidified atmosphere containing 5% co2 . bxpc-3 cells with targeted disruption of the -catenin gene ( ctnnb1 ) were established using compozr custom zinc finger nucleases ( zfns ) ( sigma - aldrich ) . briefly , following transfection of the cells with zfn mrna targeting exon 3 of the ctnnb1 gene , monoclonal cell populations were obtained by limiting dilution cloning and analyzed for -catenin expression . from 150 initial clones five -catenin gene disrupted clones negative for -catenin expression were identified and selected for further analysis ( clone # 4 , # 31 , # 79 , # 93 and # 111 ) . total rna from exponentially growing wild type bxpc-3 cells and -catenin gene disrupted clones # 4 and # 111 was isolated using the genelute mammalian total rna purification kit ( sigma - aldrich ) . the rna was subjected to microarray analysis using illumina humanht-12 v4 expression beadchips ( illumina , ca , usa ) at the norwegian genomics consortium core facility ( oslo university hospital , norway ) . for each sample 6 data extraction and quality control was performed in genomestudio ( illumina ) and the data analysis was performed using j - express . to identify the most differentially expressed genes between wild type bxpc-3 cells and the -catenin gene disrupted clones # 4 and # 111 ( average ) significance analysis of microarrays ( sam ) analysis was carried out . from the sam analysis a threshold of fold change > 2 and q - value = 0 was selected to identify the most regulated probes . in table 1 the resulting list of the 85 most differentially regulated probes is shown . to identify relevant shared biological functions associated with the identified 85 most differentially regulated transcripts , gene ontology ( go ) term enrichment analysis was done using david with the goterm_bp_2 annotation ( table 2 ) . the human pancreatic adenocarcinoma bxpc-3 ( atcc crl-1687 ) epithelial cell line was grown in rpmi-1640 ( sigma - aldrich , st louis , mo , usa ) supplemented with 10% fetal bovine serum , 1% penicillin / streptomycin and 0.002 insulin transferrin selenium ( life technologies , carlsbad , ca , usa ) cells were propagated at 37 c in a humidified atmosphere containing 5% co2 . bxpc-3 cells with targeted disruption of the -catenin gene ( ctnnb1 ) were established using compozr custom zinc finger nucleases ( zfns ) ( sigma - aldrich ) . briefly , following transfection of the cells with zfn mrna targeting exon 3 of the ctnnb1 gene , monoclonal cell populations were obtained by limiting dilution cloning and analyzed for -catenin expression . from 150 initial clones five -catenin gene disrupted clones negative for -catenin expression were identified and selected for further analysis ( clone # 4 , # 31 , # 79 , # 93 and # 111 ) . total rna from exponentially growing wild type bxpc-3 cells and -catenin gene disrupted clones # 4 and # 111 was isolated using the genelute mammalian total rna purification kit ( sigma - aldrich ) . the rna was subjected to microarray analysis using illumina humanht-12 v4 expression beadchips ( illumina , ca , usa ) at the norwegian genomics consortium core facility ( oslo university hospital , norway ) . for each sample 6 data extraction and quality control was performed in genomestudio ( illumina ) and the data analysis was performed using j - express . to identify the most differentially expressed genes between wild type bxpc-3 cells and the -catenin gene disrupted clones # 4 and # 111 ( average ) significance analysis of microarrays ( sam ) analysis was carried out . from the sam analysis a threshold of fold change > 2 and q - value = 0 was selected to identify the most regulated probes . in table 1 the resulting list of the 85 most differentially regulated probes is shown . to identify relevant shared biological functions associated with the identified 85 most differentially regulated transcripts , gene ontology ( go ) term enrichment analysis was done using david with the goterm_bp_2 annotation ( table 2 ) . we describe the dataset from the transcriptome analysis comparing wild type and -catenin deficient bxpc-3 cells . in this analysis these results together with the rest the data from the previous published article points towards a central role of -catenin in enabling cell - cell contacts in bxpc3 cells .

to study the role of wnt/-catenin signaling in pancreatic adenocarcinoma , human bxpc-3 cell lines deficient of the central canonical wnt signaling protein -catenin were established by using zinc - finger nuclease mediated targeted genomic disruption of the -catenin gene ( ctnnb1 ) . comparison of the global transcription levels in wild type cells with two -catenin gene disrupted clones identified 85 transcripts that were the most differentially regulated . gene ontology ( go ) term enrichment analysis of these transcripts identified cell adhesion as the most significantly enriched go term . here we describe the data from the transcription profiling analysis published in the article implications of targeted genomic disruption of -catenin in bxpc-3 pancreatic adenocarcinoma cells [ 1 ] . data have been deposited to the gene expression omnibus ( geo ) database repository with the dataset identifier gse63072 .

according to the world health organization , every year about 120 million people throughout the world suffer from depression . when you have depression , it 's more than feeling sad . intense feelings of sadness and other symptoms , like losing interest in things you enjoy , may last for a while . and when you have depression , it 's more than feeling sad . depression is a medical illness , not a sign of weakness . depression is a real illness with real symptoms , and it 's not a sign of weakness or something you can snap out of by pulling yourself together . the good news is that with the right support , most people can make a full recovery . depression may be caused by one factor alone or a combination of factors including biological , psychological , and environmental . depressions are considered primarily as environmental diseases with 40 - 55% of cases attributed to environmental factors and 20 - 25% genetics , 10 - 15% illness , and 5% to other factors . iran , a country with an area of about 1,873,959 km , is located between 25 40 min and 44 64 min . in this country , there are different climates and this geographical diversity has many effects on human health , weather often affects people 's moods . sunlight breaking through clouds can lift our spirits , while a dull , rainy day may make us feel a little gloomy . while noticeable , these shifts in mood generally do not affect our ability to cope with daily life . the main goal of this study was to determine the association between distribution of depression and the climatic conditions in the iran country . the depression in iran was determined by using data recorded in 2010 years by the iran registry program of the iran health center . the geographic mapping of depression and climatic conditions was then incorporated using geographic information system ( gis ) . after producing the spatial distribution model , the spatial distribution maps of depression diseases were plotted and compared and then we used neural network ( nn ) to model the trend of depression and climatic conditions . using gis software , created , and analyzed maps that showed where depression had occurred , the frequency of depression in different areas of country . gis is a method of digital ( i.e. computerized ) mapping that can show you where particular people , events , things , or conditions are , and give you other information about them as well . a gis integrates hardware , software , and data for capturing , managing , analyzing , and displaying all forms of geographically referenced information . gis allows us to view , understand , question , interpret , and visualize data in many ways that reveal relationships , patterns , and trends in the form of maps , globes , reports , and charts . a gis helps you answer questions and solve problems by looking at your data in a way that is quickly understood and easily shared . the lifetime risk for depression is 6 - 25% . according to the national institute of mental health , 9.5% or 20.9 million american adults suffer from a depressive illness in any given year . common symptoms of depression , reoccurring almost every day : depressed mood ( e.g. feeling sad or empty)lack of interest in previously enjoyable activitiessignificant weight loss or gain , or decrease or increase in appetiteinsomnia or hypersomniaagitation , restlessness , and irritabilityfatigue or loss of energyfeelings of worthlessness , hopelessness , and guiltinability to think or concentrate , or indecisivenessrecurrent thoughts of death , recurrent suicidal ideation , suicide attempt , or plan forcompleting suicide . depressed mood ( e.g. feeling sad or empty ) lack of interest in previously enjoyable activities significant weight loss or gain , or decrease or increase in appetite insomnia or hypersomnia agitation , restlessness , and irritability fatigue or loss of energy feelings of worthlessness , hopelessness , and guilt inability to think or concentrate , or indecisiveness recurrent thoughts of death , recurrent suicidal ideation , suicide attempt , or plan for completing suicide . sunlight breaking through clouds can lift our spirits , while a dull ; rainy day may make us feel a little gloomy . while noticeable , these shifts in mood generally do not affect our ability to cope with daily life . some people , however , are vulnerable to a type of depression that follows a seasonal pattern . for them , the shortening days of late autumn are the beginning of a type of clinical depression that can last until spring . sad is a pattern of major depressive episodes that occur and remit with changes in seasons . it may be seen in major depressive or bipolar disorders , as described in the diagnostic and statistical manual of mental disorders - iv . the most recognized form of sad , winter depression , is characterized by recurrent episodes of depression , hypersomnia , augmented appetite with carbohydrate craving , and weight gain that begin in the autumn and continue through the winter months . while questions regarding the validity of sad as a syndrome and the mechanism of action of light therapy continue to be investigated , the established effectiveness of light therapy in patients with winter depression supports the usefulness of assessment for this seasonal pattern and consideration of light therapy as an option in addition to existing treatment choices . although our research is classed as weather conditions , but the idea is near to this researches . however , overall 9,873,200 medical records of patients with documented pathology report of depression in 2010 were recruited from the depression registry data . it shows that depression was more abundant in north and northwest , of the country . mapping the climatic conditions depression was more prevalent in provinces of azarbayjan , mazandaran , gilan , half of golestan , ardebil , and some the other province [ figure 1 ] . the rate of depression was correlated with climatic conditions in the province , that is , it was lower in areas southern that was warmer than northern areas . climatic conditions in iran spatial distribution of depression in iran in 2010 for modeling the possibility of the depression in the 2010 future years , the nn technique was used in this research , the feed forward network for depression in 2010 was used for network training data , the independent variables , such as the input age individuals gender , population density depressed segregated city , the weather city , as well as the depression was the dependent variable . be noted that the nn analysis of multivariate regression analysis were extracted . for training network was nine repeated for 3 times after the solution has converged weight coefficients and bias of each neuron was determined [ figure 3 ] . training result fit for spatial distribution and climatic conditions in iran training and testing data were divided into two groups : depression and climatic conditions values for each group in figure can be observed [ figure 4 ] . training associated between depression and climatic conditions figure 5 shown was approximately 88% correlation between depression and climatic conditions . associated between depression and climatic conditions the lifetime risk for depression is 6 - 25% . according to the national institute of mental health , 9.5% or 20.9 million american adults suffer from a depressive illness in any given year . common symptoms of depression , reoccurring almost every day : depressed mood ( e.g. feeling sad or empty)lack of interest in previously enjoyable activitiessignificant weight loss or gain , or decrease or increase in appetiteinsomnia or hypersomniaagitation , restlessness , and irritabilityfatigue or loss of energyfeelings of worthlessness , hopelessness , and guiltinability to think or concentrate , or indecisivenessrecurrent thoughts of death , recurrent suicidal ideation , suicide attempt , or plan forcompleting suicide . depressed mood ( e.g. feeling sad or empty ) lack of interest in previously enjoyable activities significant weight loss or gain , or decrease or increase in appetite insomnia or hypersomnia agitation , restlessness , and irritability fatigue or loss of energy feelings of worthlessness , hopelessness , and guilt inability to think or concentrate , or indecisiveness recurrent thoughts of death , recurrent suicidal ideation , suicide attempt , or plan for completing suicide . sunlight breaking through clouds can lift our spirits , while a dull ; rainy day may make us feel a little gloomy . while noticeable , these shifts in mood generally do not affect our ability to cope with daily life . some people , however , are vulnerable to a type of depression that follows a seasonal pattern . for them , the shortening days of late autumn are the beginning of a type of clinical depression that can last until spring . sad is a pattern of major depressive episodes that occur and remit with changes in seasons . it may be seen in major depressive or bipolar disorders , as described in the diagnostic and statistical manual of mental disorders - iv . the most recognized form of sad , winter depression , is characterized by recurrent episodes of depression , hypersomnia , augmented appetite with carbohydrate craving , and weight gain that begin in the autumn and continue through the winter months . while questions regarding the validity of sad as a syndrome and the mechanism of action of light therapy continue to be investigated , the established effectiveness of light therapy in patients with winter depression supports the usefulness of assessment for this seasonal pattern and consideration of light therapy as an option in addition to existing treatment choices . although our research is classed as weather conditions , but the idea is near to this researches . however , overall 9,873,200 medical records of patients with documented pathology report of depression in 2010 were recruited from the depression registry data . it shows that depression was more abundant in north and northwest , of the country . mapping the climatic conditions depression was more prevalent in provinces of azarbayjan , mazandaran , gilan , half of golestan , ardebil , and some the other province [ figure 1 ] . the rate of depression was correlated with climatic conditions in the province , that is , it was lower in areas southern that was warmer than northern areas . for modeling the possibility of the depression in the 2010 future years , the nn technique was used in this research , the feed forward network for depression in 2010 was used for network training data , the independent variables , such as the input age individuals gender , population density depressed segregated city , the weather city , as well as the depression was the dependent variable . be noted that the nn analysis of multivariate regression analysis were extracted . for training network was nine repeated for 3 times after the solution has converged weight coefficients and bias of each neuron was determined [ figure 3 ] . training result fit for spatial distribution and climatic conditions in iran training and testing data were divided into two groups : depression and climatic conditions values for each group in figure can be observed [ figure 4 ] . training associated between depression and climatic conditions figure 5 shown was approximately 88% correlation between depression and climatic conditions . the paper by rosen et al . ( 1990 ) is something of a classic , finding an increasing community prevalence of sad across four locations , moving progressively north up the east coast of the usa from florida to new hampshire . more recently , mersch et al . ( 1999 ) have reviewed the relationship between sad and latitude of residence . patients with climatic conditions affective disorder have episodes of major depression that tend to recur in cold weather . although several screening instruments are available , such screening is unlikely to lead to improved outcomes without personalized and detailed attention to individual symptoms . physicians should be aware of comorbid factors that could signal a need for further assessment . cold climatic conditions affective disorder often can be treated with thermal therapy and light therapy , which appears to have a low risk of adverse effects . it remains unclear whether light and thermal are equivalent to drug therapy , whether drug therapy can augment the effects of light therapy , or whether cognitive behavior therapy is a better treatment choice . plotting the spatial distribution of depression diseases and climatic conditions showed significant associations between mapping for depression and climatic conditions distribution in the provinces of iran . we should acknowledge that in addition to the possible association of depression with climatic conditions showed significant associations between mappings for the higher prevalence of diagnosed depression might have been a result of better medical facilities and health centers in other countries of the world . however , our data comprised the records from the whole provinces including smaller cities for 1 year . according to the results of this study , not all diseases are caused by inheritance or genetic factors . in fact , environmental factors could also be responsible for some diseases such as depression . the findings of this study underscore the importance of preventing effect of climatic conditions in human health 's . control climatic conditions effecting to improve work related human health and increasing the knowledge of health professionals and the general population in this regard are also of high importance . programs aiming at lowering the depression risk will thus have to consider effective measures to reduce and exposures to effect of climatic conditions are currently .

background : neurotransmitters , such as dopamine and serotonin , play an undeniable role in the incidence of mental illnesses . almost all humans will experience depression . furthermore , most humans lack the ability to control and reduce depression , the disorder can lead to physical damage . the main goal of this study was to determine the association between distribution of depression and the climatic conditions in the iran country.methods:spatial distribution maps of depression were plotted by using data recorded during 2010 year in the iran health center registry . the geographical mapping of depression and climatic conditions were then incorporated into a geographic information system to create a spatial distribution model and in this study we used neural network to model the trend of depression and climatic conditions.results:the spatial distributions of depression diseases in the country , followed by were scattered based on climatic conditions . in fact , common depression was more prevalent in the parts of the country where cold and rainy weather was more abundant.conclusions:the findings of this study can be useful for psychologists and controlling of this disease , because lack the ability to control and reduce depression , the disorder can lead to physical damage . data are also important to establish further effects modeling for depression . moreover , psychologists and health professionals should consider the impact of environmental factors on their patients health .

volatile anesthetics improve post - ischemic recovery at the cellular level , in isolated hearts , and in animals . whether their cardioprotective effects are clinically important is still debated . according to the recent american college of cardiology / american heart association guidelines volatile anesthetics can be beneficial during non - cardiac surgery for the maintenance of general anesthesia in hemodinamically stable patients at risk for myocardial ischemia , but no evidence - based medicine exists in non - cardiac surgery . to address the question whether the choice of an anesthetic regimen might influence patients outcome after non - cardiac surgery , we have independently conducted a systematic review and meta - analysis of data pooled from existing trials to determine the impact of desflurane and sevoflurane on perioperative mi and death in patients undergoing noncardiac surgery . desflurane and sevoflurane appear to have the most prominent cardioprotective properties in experimental studies and are the only anesthetic drugs that reduce morbidity and mortality in surgical patients . the full pubmed search strategy was developed according to biondi - zoccai et al , and is available in the appendix . no language restriction was enforced and non - english - language articles were translated before further analysis . references obtained from database and literature searches were first independently examined at the title / abstract level by four trained investigators with divergences resolved by consensus , and then , if potentially pertinent , retrieved as complete articles . the following inclusion criteria were employed for potentially relevant studies : random allocation to treatment , comparison of a total intravenous anesthesia ( tiva ) versus an anesthesia plan including administration of desflurane or sevoflurane , performed in cardiac surgery with no restriction in dose and time of administration . the exclusion criteria were : duplicate publications , studies conducted in cardiac surgery , studies on pediatric patients , non - human experimental studies . four investigators , independently assessed compliance to selection criteria and selected studies for the final analysis , with divergences finally resolved by consensus ( table 1 ) . des : desflurane ; sevo : sevoflurane ; pts : number of patients ; ent : ear - nose - throat ; gyn : gynecological ; lps : laparoscopic ; cea : carotid endoarterectomy ; nr : non reported . data abstraction and study characteristics baseline , procedural and outcome data were independently abstracted by four trained investigators with divergences resolved by consensus . specifically , we extracted study end - points and main outcomes ; study design ( including patient selection , randomization , single-/multi - center design , open or single-/double - blind design ) ; clinical setting ; population ; anesthetic protocol ; choice of intravenous anesthetics ; adverse events . at least two attempts at contacting original authors via electronic or conventional mail was made in case of missing data . the primary end - point of the present review was the rate of in - hospital mi as per author definition while the co - primary end - point was the rate of hospital mortality . secondary endpoints were : peak cardiac troponin release , cardiac adverse events other than mi ( arrhythmias , heart failure ) , intensive care unit ( icu ) and hospital stay , time on mechanical ventilation , other major adverse events ( renal failure , respiratory failure . data analysis and synthesis computations were performed with revman 4.2 ( a freeware available from the cochrane collaboration ) . statistical heterogeneity and inconsistency was measured using , respectively , cochran q tests and i2 . binary outcomes from individual studies were analyzed in order to compute individual and pooled odds ratios ( or ) with pertinent 95% confidence intervals ( ci , with equivalence set at 1 , or<1 favoring the first treatment , and or>1 favoring the second treatment ) , by means of the peto fixed effect method in case of low statistical inconsistency ( i225% ) and by means of a random effect method ( which better accommodates clinical and statistical variations ) in case of moderate or high statistical inconsistency ( i2>25% ) . weighted mean differences ( wmd ) and 95% ci were computed for continuous variables , again by means of a fixed effect method in case of low statistical inconsistency ( i225% ) and by means of a random effect method in case of moderate or high statistical inconsistency ( i2>25% ) . statistical significance was set at the two - tailed 0.05 level for hypothesis testing and at 0.10 for heterogeneity testing , and unadjusted p values are reported throughout . this study was performed in compliance with the cochrane collaboration and the quality of reporting of meta - analyses ( quorom ) guidelines . database searches , snowballing and contacts with experts yielded a total of 4281 citations . excluding 3936 non - pertinent titles or abstracts , we retrieved in complete form and assessed according to the selection criteria 344 studies . a total of 265 studies were further excluded according to our exclusion criteria ( figure 1 ) . we finally identified 79 eligible randomized clinical trials , which were included in the final analysis ( table 1 ) ( complete references are available from the authors for readers ) . study characteristics the 79 included trials randomized 6219 patients ( 2768 to tiva and 3451 receiving desflurane or sevoflurane in their anesthesia plan ) . ( table 1 ) all studies used propofol as the main hypnotic agent in the tiva group . surgical settings varied across studies and included vascular , thoracic , orthopedic , general , gynecological , urological , ear - nose - throat , bariatric , ophthalmic , surgery and neurosurgery . nineteen studies were conducted in day - surgery settings . all authors administered volatile or intravenous anesthetics throughout the procedure . volatile anesthetic dosage varied across studies , ranging 0.33 - 2 mac in the 609 patients receiving desflurane and 0.25 - 2 mac in the 2842 patients receiving sevoflurane . all studies had a single - center design , and included populations which were too small to allow for significant results in clinical relevant outcome variables . study quality appraisal showed that most studies appeared of suboptimal quality , as testified by the common lack of details on the method used for randomized sequence generation and allocation . only a handful of randomized controlled trials ( rcts ) were of high quality , while many others lacked important details to appraise the risk of selection , performance , attrition , or detection biases . quantitative data synthesis no author reported any postoperative myocardial infarction or death among the study population , nor any significant cardiac adverse event . no difference in the incidence of arrhythmias ( 81/769 [ 10.5% ] in the volatile anesthetics group vs 69/736 [ 9.4% ] in the control arm , or=1.14 [ 0.80 - 1.62 ] , p for effect=0.48 , p for heterogeneity=0.28 , i2=15.5% ) was noted ( figure 2 ) . pooled estimators of incidence of intraoperative arrhythmias . hospital stay was identical between groups ( wmd 0.01 days [ -0.06 , 0.07 ] , p for effect=0.88 , p for heterogeneity = 0.48 , i2=0% with 1201 included patients ) . nineteen out of eighty authors answered our request for additional data , and responses confirmed that no deaths or myocardial infarctions were observed among their patients . when directly interrogated as to why they did not include cardiac adverse events in their reports , 16% of authors answered that they were not aware of the cardioprotective properties of halogenated anesthetics , 63% that they did not observe any adverse event during their study and decided not to report it , and 21% replied that they did not monitor patients for cardiac complications . we performed a meta - analysis of pooled data from several small , underpowered studies to demonstrate whether the cardioprotective properties of desflurane and sevoflurane could decrease the rate of mi and death in patients undergoing non - cardiac surgery . we found that comparison between halogenated agents and propofol in non - cardiac surgery in terms of cardiac morbidity and mortality is , so far , unattainable because of lack of published data . postoperative mortality and myocardial infarction rate were either null or non reported in all studies included in our meta - analysis . desflurane and sevoflurane have been recently shown to reduce incidence of morbidity and mortality following cardiac surgery : a meta - analysis found a 4-fold decrease of mortality ( 0.4% vs 1.6% , p=0.02 ) and a 2-fold decrease of myocardial infarctions ( 2.4% vs 5.1% , p=0.008 ) . the authors also found advantages in terms of ctn release , icu and overall hospital stay , need for inotropic support and mechanical ventilation , and one - year major cardiac events . multicentre experiences had previously demonstrated that halogenated anesthetics reduce ctn release following coronary artery bypass grafting surgery , while discordant results exist in valvular surgery and a pilot study yielded no results in patients undergoing stenting procedures . whether these cardioprotective properties also exist in noncardiac surgical settings is still controversial , owing to the scarce available data . the use of volatile anesthetics for hemodynamically stable patients at risk for myocardial ischemia undergoing noncardiac surgical procedures has recently been recommended as a class of evidence iia , level b , but no prospective or retrospective study supports this recommendation . previous meta - analyses on volatile and intravenous anesthetics in non - cardiac surgery did not investigate clinically relevant outcomes , focusing on induction characteristics , postoperative recovery times and incidence of postoperative nausea and vomiting ( ponv ) . most authors agreed that propofol reduces ponv , while awakening and extubation times appear to be shorter in patients treated with halogenated anesthetics . we believe that , while it is important to ascertain the quality of our daily work in terms of patient comfort before , during and after surgery , but it is vital to understand what tools we have to influence the very outcome of our patients . in a recently published review , bassi et al compared the outcome of patients undergoing one - lung ventilation under either intravenous or inhalational anesthesia , and reached our same conclusions : it was impossible to conduct a meta - analysis because no author reported patient outcome . most studies were of poor quality , and this made it impossible to use analytical methods in order to reach a solid result . the observation that volatile anesthetics have cardioprotective properties that last after their elimination led to the concept of pharmacological preconditioning or anesthetic preconditioning . these properties are enhanced by their administration in the reperfusion phase and seem to be related to their timing and modalities of administration during cardiac surgery . all volatile anesthetics induce a dose - dependent decrease in myocardial contractility and cardiac loading conditions . these depressant effects decrease myocardial oxygen demand and may , therefore , have a beneficial role on the myocardial oxygen balance during myocardial ischemia . experimental evidence has clearly demonstrated that in addition to these indirect protective effects , volatile anesthetic agents also have direct protective properties against reversible and irreversible ischemic myocardial damage . these properties have not only been related to a direct preconditioning effect but also to an effect on the extent of reperfusion injury . since the mechanisms that lead to anesthetic preconditioning are not fully understood yet , it can not be excluded that the protective effects of desflurane and sevoflurane that have been observed may be due to properties other than preconditioning alone . the fact that none of the included studies encountered any major adverse event suggests that postoperative death and mi were both poorly reported and/or adjudicated in the analyzed studies . while this may weaken the results of our meta - analysis , it strengthens our opinion that patient outcome should never be forgotten in clinical studies . volatile anesthetics have low costs and carry very few risks , and have been demonstrated to reduce morbidity and mortality following cardiac surgery . in contrast to recent guidelines , the results of our study can not support the hypothesis that their routine use can reduce perioperative myocardial injury in non - cardiac surgery . the fact , however , that no cardiac protection by desflurane or sevoflurane could be shown in this analysis does not mean that these substances do not provide such protection in high risk patients undergoing non - cardiac surgery : it does , instead , stress the scarce awareness among anesthesiologists that patient outcome can be affected by our anesthetic plan . large , multicentre , randomized clinical trials including patients undergoing high - risk non - cardiac surgery and reporting data on clinically relevant outcomes are needed to achieve a demonstration of anesthetic - induced cardioprotection : this represents a difficult task because of the low mortality rate in modern surgery , and because of the number of interfering factors . ( randomized controlled trial[pt ] or controlled clinical trial[pt ] or randomized controlled trials[mh ] or random allocation[mh ] or double - blind method[mh ] or single - blind method[mh ] or clinical trial[pt ] or clinical trials[mh ] or ( clinical trial[tw ] or ( ( singl*[tw ] or doubl*[tw ] or trebl*[tw ] or tripl*[tw ] ) and ( mask*[tw ] or blind[tw ] ) ) or ( latin square[tw ] ) or placebos[mh ] or placebo*[tw ] or random*[tw ] or research design[mh : noexp ] or comparative study[mh ] or evaluation studies[mh ] or follow - up studies[mh ] or prospective studies[mh ] or cross - over studies[mh ] or control*[tw ] or prospectiv*[tw ] or volunteer*[tw ] ) not ( animal[mh ] not human[mh ] ) not ( comment[pt ] or editorial[pt ] or meta - analysis[pt ] or practice - guideline[pt ] or review[pt ] ) ) and ( desfluran * or sevofluran * or propofol * ) and ( cardiac and ( operation or intervention or surgery or bypass ) ) ) .

introductionvolatile anesthetics improve post - ischemic recovery . a meta - analysis suggested that the cardioprotective properties of desflurane and sevoflurane could reduce mortality and cardiac morbidity in cardiac surgery . recent american college of cardiology / american heart association guidelines recommended volatile anesthetic agents during non - cardiac surgery for the maintenance of general anesthesia in patients at risk for myocardial infarction but whether these cardioprotective properties exist in non - cardiac surgery settings is controversial . we therefore performed a meta - analysis of randomized studies to investigate this issue.methodstwo investigators independently searched pubmed . inclusion criteria were random allocation to treatment , comparison of a total intravenous anesthesia regimen vs an anesthesia plan including desflurane or sevoflurane , performed on adult patients undergoing non - cardiac surgery . the primary endpoints were the incidence of perioperative myocardial infarction and death.resultsa total of 6219 patients from 79 randomized trials were identified . no myocardial infarctions or deaths were reported in any of the studies we examined.conclusionsthis meta - analysis highlights a weakness in the literature and the results can be used to design future studies : the cardioprotective properties of desflurane and sevoflurane have never been studied in noncardiac surgery . no randomized study , among those which compared desflurane or sevoflurane to intravenous anesthetics , has addressed major outcomes such as myocardial infarction or mortality . large , multicentre , randomized clinical trials including patients undergoing high - risk non - cardiac surgery and reporting clinically relevant outcomes such as myocardial infarction and mortality are needed .

in several studies carried out on the incidence of nosocomial infections , urinary tract infections ( uti ) were the most frequent and consisted more than 40% of all hospital infections ( 1 - 7 ) . in spite of the broad spectrum antibiotics use , utis are still a cause of considerable morbidity and mortality in the modern medicine . utis are usually associated with urinary catheters ( uc ) or urologic procedures ( 8 - 10 ) . urinary catheterization is one of the main measures used for the treatment and caring for hospitalized patients . it is associated with the emergence of bacteria in the urine , unpleasant symptoms , and complications that can reduce the quality of health care services ( 11 ) . despite considerable advancements in manufacturing medical devices such as ucs , infections caused by these devices are common , costly , and can cause significant patient morbidity ( 2 , 12 ) . the pathogenesis of infections caused by medical devices is not well understood and a variety of factors are considered such as susceptibility of the host and the microorganisms ability to attach to the medical devices ( 8) . biofilm formation begins immediately after catheter insertion , when organisms adhere to a conditioning film of host proteins which forms along the catheter surface . bacteria usually originate from the periurethral area or ascend the drainage tubing following colonization of the drainage bag ( 13 ) . there are different types of ucs in terms of their materials , sizes and shapes and each of them is made for a specific purpose . the aim of this diversity is to reduce the risk of uti ( 4 , 14 ) . ucs are also categorized considering their location and duration of use ( 15 ) . due to the fact that in some patients , such as those admitted to the intensive care units , the ucs should long remain in the bladder , a variety of specialized antiseptic / antibiotic impregnated catheters have been designed to reduce the risk of uti ; but they are expensive and not available in some medical centers ( 16 ) and some studies showed these catheters did not reduce symptomatic uti ( 17 ) . however , due to the existence of latex with these catheters , changes in bladder tissue , infections , and in some cases hemorrhagic cystitis has been reported . thus , in some studies it has recommended that nelatone catheters should be substituted for ordinary foley catheters to prevent these complications ( 18 ) . due to the fact that there are no studies to compare the complications of these two types of ucs according to the laboratory tests and urine cultures , this study aimed to compare the rates of uti in rabbits catheterized either with foley or nelatone catheters . this experimental study was conducted at kashan university of medical sciences from july to september 2013 . in this study , 60 five - months - old new zealand male rabbits weighing 2 to 2.5 kilograms were randomly assigned to three groups of twenty . one week before study , animals were fed similarly and were kept at 21 1c with 12 hour light / dark cycle ( lights on from 8:00 am to 8:00 pm ) . twenty rabbits were catheterized using nelatone catheters ( no : 8 , made by vrp co , malaysia ) ; the second group were catheterized using foley catheters ( no : 8 , made by vrp co , malaysia ) . for catheterization , the animal was placed in a horizontal dorsal decubitus position on the surgical table and its paws were fixed to the extremities of the table with thin ropes . the catheters were installed by a surgery resident using correct technique of aseptic catheter insertion and measures for instant , adhesive fabric for fixation and use of lubricant gel for inserting the catheter into urethra were carefully performed under sterile condition . urine samples ( i.e.1 ml ) were collected from all the three groups through suprapubic method under aseptic conditions . the specimens were immediately sent to the laboratory and cultured on blood agar medium . based on the result of urine cultures , a uti was diagnosed when one or more organisms were present at quantitative counts of greater than or equal to 100 colony - forming units ( cfu ) per milliliter . all data were documented in a checklist consisting items on the name of group , the code of rabbit , the number of cfu in the urine culture and the type of the bacteria grew in the culture medium . animal handling and all experiments were performed in accordance with the international guidelines set out in the guide for the care and use of laboratory animals ( institute of laboratory animal resources , 1996 ) ( 19 ) and the helsinki declaration has been respected . the study protocol was approved by the local research council and the research ethics committee at kashan university of medical sciences , kashan , iran . all information was extracted from data registration forms and the data were entered into spss 13.0 software . animal handling and all experiments were performed in accordance with the international guidelines set out in the guide for the care and use of laboratory animals ( institute of laboratory animal resources , 1996 ) ( 19 ) and the helsinki declaration has been respected . the study protocol was approved by the local research council and the research ethics committee at kashan university of medical sciences , kashan , iran . all information was extracted from data registration forms and the data were entered into spss 13.0 software . no positive urine cultures were found in the control group . the number of uti were four cases in the nelatone group and 12 cases in the foley group ( p = 0.01 ) ( table 1 ) . the frequency of entrococcal infection was less in the nelatone group ( 3 cases ) compared with the foley group ( nine cases ) and this difference was statistically significant ( p = 0.038 ) . moreover , three cases of staphylococcal uti were observed in the foley group compared to only one case in the nelatone group ( p = 0.605 ) ( table 2 ) . in this study , uti was observed in the both intervention groups but no infection was observed in the control group . there were significant differences between the two types of catheters in causing uti and the nelatone catheter was associated with a lower risk of uti . these studies only assessed the risk of developing uti after inserting a uc and have reported conflicting results . have studied 8169 patients with ucs and reported that the long - term exposure to a uc is a definite risk factor for development of uti . they suggest that further investigation is warranted to determine the other factors affecting uc associated utis ( 20 ) . consistent with results of the present study , uckay et al . confirmed that a higher rate of uti should be expected in patients who undergo urinary catheterization . however , they did not investigate the difference in the rates of uti in patients with different types of ucs . on the other hand , smarick et al . studied the incidence of catheter - associated uti in dogs and reported that placement of an indwelling uc is associated with a low risk of uti in dogs . they also reported that the results of bacterial culture of uc tips can not predict the development of catheter - associated utis ( 21 ) . ( 16 ) and nicolle ( 13 ) have also observed no significant difference between silicone and latex catheters regarding the risk of uti . ( 4 ) who reported that there is not enough evidence on superiority of different types of catheters on each other considering the risk of uti in hospitalized patients with short - term catheterization . these studies along with our results show the necessity to determine the factors affecting the rate of tuis in catheterized patients . the most effective way to prevent infection is to limit catheter use and discontinue the catheter when no longer needed . catheter removal or exchange might also be useful in management of uti associated with ucs ( 7 ) . nurses can help to prevent catheter - associated utis through using aseptic technique on insertion , follow best practice in ongoing care and prompt removing of catheters ( 22 ) . some researchers indicate that antibiotic prophylaxis significantly reduced the rate of catheter - associated utis ( 23 , 24 ) but guidelines do not recommend routine use of antibiotics ( 23 , 25 ) or antimicrobial coated catheters ( 13 , 25 ) to prevent catheter - associated utis . in the present study , the microorganisms isolated from the rabbits with uti , were enterococcus and staphylococcus . however , in a study on patients with symptomatic uti , escherichia coli ( e. coli ) , klebsiella pneumoniae , pseudomonas aeruginosa , acinetobacter spp , staphylococcus , enterococcus and gram - negative bacteria were the most common isolated organisms ( 26 ) . in two other human studies , e. coli was the predominant organism isolated from catheterized patients ( 27 , 28 ) . nonetheless , in an animal study , e. coli and proteus spp . were more frequent in non - catheterized dogs , whereas enterobacter spp . and evidence show that the patients ' skin and high - touch environmental surfaces are important sources for contamination of ucs in place , in hospitalized patients ( 30 ) . in this study , we conducted an investigation to identify the most appropriate catheter ( foley vs. nelatone ) for short - term urinary catheterization in animal model . we did not evaluate bladder histological changes in our animals and this would be one of the weaknesses of the present study . in conclusion , there was a significant difference between nelatone and foley catheters in producing utis . using nelatone catheters bear a far lower risk of infection . considering the high prevalence of uti after long - term use of a ucs in hospitalized patients and the subsequent prolonged hospitalization and health care financial burdens , it can be suggested that nelatone catheters may be used instead of foley ones . further investigation is warranted to determine the effectiveness of the type of the uc and the appropriate type of catheter for each patient .

background : urinary catheterization is one of the main measures used to treat and care for hospitalized patients . several complications have been attributed to the presence of latex with routine foley catheters . therefore , some studies have recommended that nelatone catheters be substituted for the ordinary foley catheters to prevent these complications.objectives:this study aimed to compare the rates of urinary tract infection ( uti ) in rabbits catheterized either with foley or with nelatone catheters.materials and methods : a randomized controlled trial was conducted on 60 rabbits that were randomly assigned to three groups of twenty . the first group was catheterized using nelatone catheter ; the second group was catheterized using foley catheter and the third group was studied without performing any catheterization . after seven days , urine samples were collected using suprapubic aspiration and were sent to the laboratory for culture . descriptive statistics were calculated . moreover , chi - square and fisher s exact tests were used for data analysis.results:at the end of the study , four cases in the nelatone group and 12 cases in the foley group presented with uti ( p = 0.01 ) . no positive urine cultures were found in the control group.conclusions:the nelatone catheters , compared with the foley ones , had a lower risk of uti in the long term use . verifying this claim by further studies can have an important role in reducing utis in patients using urinary catheters .

xeroderma pigmentosum ( xp ) is a rare autosomal recessive disorder of dna repair , with a prevalence of 1 in 1 million . it may also be a cause of neurological symptoms including sensorineural hearing loss , peripheral neuropathy , ataxia , and chorea . severe neurological symptoms including mental retardation , short stature , and hypogonadism invoke de sanctis - cacchione syndrome ( dcs ) . the patient was a 55-year - old woman with a history of mental retardation who developed chorea at age 32 and ataxia at age 37 . she had numerous facial scars from 10 prior basal cell carcinoma excisions as well as diminished deep tendon reflexes , bilateral hearing loss , dysphagia , and skin freckling . supportive treatment and prevention of further damage from uv light is the mainstay of treatment in xp and dcs . xp and related disorders should be considered in the setting of neurological disorder and multiple cutaneous cancers . xeroderma pigmentosum ( xp ) is a rare autosomal recessive disorder of dna repair , with a prevalence of 1 in 1 million . affected patients are at 1,000 times higher risk to develop basal cell carcinoma , squamous cell carcinoma , and malignant melanoma . xp may also be a cause of neurological symptoms including sensorineural hearing loss , peripheral neuropathy , ataxia , and chorea . severe neurological symptoms including mental retardation , short stature , and hypogonadism invoke de sanctis - cacchione syndrome ( dcs ) . the patient was a 55-year - old female who presented for evaluation of incoordination and gait disturbance . she had some learning disabilities , especially concerning visuospatial tasks , but was able to finish high school and earn a college degree with special education accommodations . at age 32 ataxic gait developed at age 37 , at which time she was noted to walk as if she were intoxicated . she began to use a rolling walker at age 50 and required a wheelchair at age 52 . family history is significant for a second cousin ( i.e. with shared great - grandparents ) with amyotrophic lateral sclerosis , which in retrospect could have been dcs progressing to quadriparesis . on initial examination she had diffuse skin freckling . on mental status examination , she was alert and oriented to person and doctor 's office , but not to date . she was very anxious and perseverated on statements such as being afraid of falling out of her wheelchair or requesting to go to the bathroom . she was able to perform the luria sequence only by directly copying the examiner , and even those attempts were partially complicated by motor perseveration . on eye movement examination , saccade initiation and velocity were diminished . there were intermittent side - to - side and up - and - down head movements which were most likely titubation secondary to cerebellar dysfunction . in addition , there was moderate finger - to - nose dysmetria and bilateral upper extremity dysdiadochokinesis as well as involuntary movements likely due to a combination of ataxia and possible proprioceptive sensory loss ( for online suppl . she was able to protrude her tongue for 10 s , demonstrating a lack of motor impersistence . there was severe postural instability ; hence , she was able to stand up only with assistance . laboratory testing was negative for the huntington 's disease gene as a cause of chorea . a paraneoplastic antibody panel for anti - ri , yo , cancer - associated retinopathy , zic4 , amphiphysin , cv2 , hu , ma , ta , voltage - gated potassium channel , p / q type voltage - gated calcium channel , glutamic acid decarboxylase , nmda receptor ( nr1 ) , and ganglionic nicotinic acetylcholine receptor ( athena diagnostics , worcester , mass . , additional commercially available genetic testing was negative for spinocerebellar ataxia ( sca1,sca2,sca3,sca6,sca7,sca8,sca10 , and sca17 ) , dentatorubral - pallidoluysian atrophy ( drpla ) as well as ataxia with oculomotor apraxia type 1 ( aprataxin / aptx ) and type 2 ( senataxin / setx ) , marinesco - sjgren syndrome ( sil1 ) , sensory ataxic neuropathy , dysarthria , and ophthalmoparesis ( sando / polg1 ) , ataxia with isolated vitamin e deficiency ( aved / ttpa ) , and friedreich 's ataxia ( frda ) ( athena diagnostics ) . neuroacanthocytosis is a concern in the setting of mental retardation , possible peripheral neuropathy , and chorea , but a blood smear was negative for acanthocytes . there were no intracranial calcifications on computed tomography of the head , arguing against cockayne syndrome ( cs ) . genetic testing for causative genes has not been performed because commercial testing is not available in the usa . at age 55 , anxiety improved after starting escitalopram , but this medication had to be stopped after an episode of liver enzyme elevation . given that an attempt to install a coating on her home windows to block uv light was unsuccessful for technical reasons , she was instructed to spend as much time as possible in the interior rooms of the house which do not have direct sunlight . dna repair problems were identified as a cause of xp by cleaver in 1969 . there is a defect in nucleotide excision repair removing pyrimidine dimers produced by uv light . about 20% of xp cases may have associated neurological symptoms [ 3 , 8 ] . decreased deep tendon reflexes , hearing loss , ataxia , and chorea xp complementation groups a , b , c , d , e , f , g , and v exist . dcs may be considered a severe subtype of xp complementation groups a or d , with mutations in xpa or ercc2/xpd . older descriptions of dcs also include features of microcephaly , choreoathetosis , ataxia , sensorineural deafness , and progression to quadriparesis with shortening of the achilles tendons . cutaneous photosensitivity , microcephaly , mental retardation , short stature , hypogonadism , spasticity , peripheral neuropathy , and sensorineural deafness . in contrast to xp and dcs , classic clinical cs phenotype includes intracranial calcification , normal to increased deep tendon reflexes , and an absence of cutaneous cancer . the csb gene was initially discovered in cs , but identical csb mutations can , peculiarly , also cause xp and dcs . hence , there is considerable phenotypic heterogeneity . in addition , there is a genetic and clinical overlap between xp , trichothiodystrophy ( ttd ) and cs . ttd is in the differential diagnosis , but less likely given the absence of brittle hair and ichthyosis . other ttd symptoms include photosensitivity , intellectual impairment , short stature , microcephaly , brain demyelination , protruding ears , and micrognathia . global cortical , brainstem , and cerebellar atrophy similar to this case were demonstrated in a case report by mittal et al . . while hyperostosis frontalis interna may be a benign incidental finding , interestingly it was also present on images in that case report . supportive treatment and prevention of further damage from uv light is the mainstay of treatment for dermatological manifestations of xp and dcs . xp and related syndromes should be considered in the setting of neurological disorder and multiple skin cancers .

introductionxeroderma pigmentosum ( xp ) is a rare autosomal recessive disorder of dna repair , with a prevalence of 1 in 1 million . it may also be a cause of neurological symptoms including sensorineural hearing loss , peripheral neuropathy , ataxia , and chorea . severe neurological symptoms including mental retardation , short stature , and hypogonadism invoke de sanctis - cacchione syndrome ( dcs).case reportthe patient was a 55-year - old woman with a history of mental retardation who developed chorea at age 32 and ataxia at age 37 . she had numerous facial scars from 10 prior basal cell carcinoma excisions as well as diminished deep tendon reflexes , bilateral hearing loss , dysphagia , and skin freckling . brain mri revealed severe cortical , cerebellar , and brainstem atrophy . supportive treatment and prevention of further damage from uv light is the mainstay of treatment in xp and dcs.conclusionxp and related disorders should be considered in the setting of neurological disorder and multiple cutaneous cancers .

they act by the closure of katp channel in pancreatic -cells which results in membrane depolarization , calcium influx in -cells , and subsequent insulin release . katp channel is composed of four pore forming potassium inward rectifier 6.2 ( kir6.2 ) subunits encoded by kcnj11 gene . the external part of the channel is constituted by four sulfonylurea receptor 1 ( sur1 ) subunits encoded by abcc8 gene . nonsynonymous variants kcnj11 e23k and abcc8 s1369a were identified which are in strong linkage disequilibrium . pharmacogenetic studies showed stronger effect of sulfonylureas , predominantly gliclazide , in the carriers of the genotypes kcnj11 k23 and/or abcc8 a1369 [ 46 ] . single nucleotide polymorphisms ( snps ) of gene encoding transcription factor 7-like 2 ( tcf7l2 ) were shown to have the strongest association with type 2 diabetes among all diabetes associated gene snps . the risk of developing diabetes is twice as high as that in homozygous carriers of the risk genotypes in comparison with homozygous carriers of common variants [ 7 , 8 ] . functional studies showed that tcf7l2 risk variants were associated with decreased insulin secretion [ 9 , 10 ] . pharmacogenetic studies reported a significant association between tcf7l2 risk variants and lower effect of sulfonylurea treatment [ 1113 ] . it binds exclusively on the a - site while the majority of other commonly used sulfonylureas bind to the ab - site of the katp channel . recently , it was observed in a study on cell lines that katp channel is more sensitive to inhibition by gliclazide , but not glimepiride , glibenclamide , or glipizide ( all ab - site binding drugs ) in the carriers of k23/a1369 risk haplotype in comparison with the carriers of e23/s1369 haplotype . we hypothesized that a difference might exist also in tcf7l2 genotype effect on glucose reduction between gliclazide and the ab - site binding sulfonylureas . the aim of the present study was to compare genotype effect on the hba1c reduction in the group of patients treated with gliclazide with the group of patients who used ab - site binding sulfonylureas one hundred and one patients ( 50 males and 51 females ) of central european caucasian origin were recruited from three outpatient clinics . patients were eligible for the study if they were on previous metformin monotherapy for at least 6 months and failed to maintain hba1c < 7.0% on maximal tolerated doses of metformin at two consecutive visits within a three - month period . inclusion criteria were hba1c of 7.0%11.0% , age 3570 years , and body mass index ( bmi ) 2035 kg / m . patients with malignancies , endocrine disorders , chronic renal failure , severe liver disease , systemic inflammatory disease , and corticosteroid treatment were excluded . the ethical approval for this study was obtained from the l. pasteur university hospital review board . all participating subjects gave a written consent to the study . at the baseline visit , anthropometric data , as well as the diabetes duration and metformin treatment duration , sulfonylurea treatment was started with 25%50% of maximum approved dose for the specific sulfonylurea . a total 55 of patients were treated with gliclazide , and 46 patients were treated with the sulfonylureas binding to katp channel ab - site : 29 patients with glimepiride , 14 patients with glibenclamide , and 3 patients with glipizide . if hba1c level < 7% was not reached after 3-month therapy , doses could have been increased up to 100% of the approved dose for the specific sulfonylurea compound . mean sulfonylurea dose prescribed at the 3-month visit was 47 2% of maximum approved dose for specific drug . the main study outcome was the difference between hba1c level and baseline hba1c ( hba1c ) following 6-month therapy with sulfonylurea . in all patients , genomic dna was extracted using a wizard genomic dna purification kit ( promega corp . , pcr was performed in 10 l of reaction volume on lightscanner 32 instrument ( idaho technology inc . , master mix comprised of 0.2x lcgreen plus+ ( idaho technology inc . ) , 200 m dntps ( jena bioscience , jena , germany ) , 0.05 m forward primer , 0.5 m reverse primer , 1 m unlabeled blocked probe , 3 mm mgcl2 , 1u biothermab polymerase with 1x corresponding buffer ( genecraft , mnster , germany ) , and approximately 10 ng dna . the sequences of oligonucleotides ( sigma - aldrich , germany ) were the following : 5-ctctgcctcaaaacctagcaca-3 ( forward primer ) , 5-gtctgaaaactaagggtgcctcat-3 ( reverse primer ) , 5-gcactttttagatactatataatttaattgcc-3phos ( probe ) . pcr conditions were the following : initial denaturation at 95c for 5 min , 55 cycles at 95c for 10 s , 64c for 10 s , and 72c for 10 s. amplification was performed at the thermal transition rate of 10c / s for all steps and was immediately followed by melting analysis with a denaturation at 95c for 30 s and renaturation at 45c for 1 minute . data were acquired over 5090c range at the thermal transition rate of 0.1c / s . genotypes were identified by the melting temperatures of probe peaks on the normalized derivative plots using lightscanner 32 software 1.0.0.23 ( idaho technology inc . ) . 5-ctctgcctcaaaacctagcaca-3 ( forward primer ) , 5-gtctgaaaactaagggtgcctcat-3 ( reverse primer ) , 5-gcactttttagatactatataatttaattgcc-3phos ( probe ) . statistical analyses were performed using spss 17.0 for windows software ( spss inc . , the continuous variables are presented as mean standard error of mean ( sem ) . for the comparison of continuous variables , unpaired / paired student 's t - test and analysis of variance ( anova ) with post - hoc comparisons -test was used to test the hardy - weinberg equilibrium and for comparison of gender representation . multivariate linear models were used for the testing of the response of hba1c to sulfonylurea according to the genotypes . all models were adjusted for the age at the beginning of sulfonylurea treatment , gender , baseline bmi , baseline hba1c , sulfonylurea type , and sulfonylurea dose which was standardized as a percentage of maximal doses for the specific sulfonylurea . anthropometric and biochemical characteristics of all study subjects and groups of patients treated either with gliclazide ( group 1 ) or with ab - site binding sulfonylureas ( group 2 ) are shown in table 1 . no significant difference was observed in gender representation , average age , bmi , diabetes duration , baseline hba1c , hba1c after 6 months , and sulfonylurea dose between the two groups . there was no significant difference between both groups in the average hba1c following 6-month therapy with sulfonylurea ( table 1 ) . a total of 51 patients were homozygous for wild type c - allele ( cc genotype ) , 41 patients were heterozygous ( ct genotype ) , and 9 patients were homozygous for the type 2 diabetes associated t - allele ( tt genotype ) of tcf7l2 rs7903146 . clinical characteristics of the study group according to the tcf7l2 genotypes are displayed in table 2 . after 6 months of the sulfonylurea therapy , a significant difference among the genotypes in relation to hba1c was observed in both the entire study group and the gliclazide treated subgroup ( group 1 ) , while no significant difference in effect among the genotypes was observed in group 2 ( table 3 ) . the biggest reduction in hba1c was observed in cc genotype group , while the reductions were similar in both ct and tt genotype groups suggesting possible dominant way of inheritance ( table 3 ) . further analyses using dominant genetic model showed significantly higher effect of gliclazide in the cc genotype group on hba1c reduction in comparison with combined ct + tt genotype group ( 1.32 0.15% versus 0.73 0.11% , p = 0.003 , p = 0.005 ) . in contrast , no significant difference in hba1c between the patients with cc genotype and t - allele carriers was observed in group 2 ( table 3 ) . in the multiple linear regression model with hba1c as dependent variable , tcf7l2 genotype , age , gender , bmi , baseline hba1c , sulfonylurea group , and sulfonylurea dose were included as independent variables ( table 4 ) . in this model the tcf7l2 genotype ( p = 0.006 ) and the baseline hba1c ( p < 0.001 ) were the only significant predictors of hba1c ( r = 0.56 ) . after introducing the interaction term between tcf7l2 genotype and sulfonylurea treatment group to the model , the variance explained by the model increased ( r = 0.58 ) and the interaction term became a significant predictor ( p = 0.023 ) of hba1c ( table 4 ) . the main finding of the present study is a significant interaction found between tcf7l2 genotype and the type of sulfonylurea used in the treatment of the patients with type 2 diabetes . the patients treated with gliclazide had significantly stronger genotype specific effect with the average reduction in hba1c in homozygous carriers of common c - allele higher by 80% than in - risk t - allele carriers . no significant genotype effect was observed in the group of patients treated by glibenclamide , glimepiride , or glipizide . to the best of our knowledge , only three studies analyzed the effect of sulfonylurea treatment in relation to tcf7l2 genotype . pearson et al . found higher probability of sulfonylurea failure and smaller reduction in hba1c in tcf7l2 rs1225372 and rs7903146 risk allele carriers in a group of 901 patients included in the genetics of diabetes audit and research tayside study ( godarts ) . the results observed in godarts were replicated independently by two central european groups [ 12 , 13 ] . in none of the mentioned studies , the present study extends the current knowledge by demonstrating the first observation of the different tcf7l2 genotype effect of various sulfonylureas with the strongest genetic specificity observed in gliclazide users in contrast to the patients treated with other sulfonylurea drugs , as proved by the test of interaction . the explanation of this difference might lie in the different pharmacodynamic characteristics of gliclazide and the other studied sulfonylureas . beside the mentioned katp channel some studies relate the tcf7l2 effect to the action of incretin hormones glucagon - like peptide 1 ( glp-1 ) and glucose - dependent insulinotropic peptide ( gip ) . these hormones stimulate cells primarily by the activation of the camp - dependent pathway . interestingly , it was recently shown that beside their effect on closure of katp channel , the majority of sulfonylureas also activate the exchange protein activated by camp 2 ( epac2 ) which subsequently activates small g - protein rap1 . epac2/rap1 signaling is essential for potentiating the first phase of insulin release . while in studies in animals and cell lines tolbutamide , glibenclamide , chlorpropamide , and glipizide were able to activate epac2/rap1 signaling , gliclazide did not activate this pathway [ 14 , 20 ] . because the t - allele at tcf7l2 rs7903146 has been shown to be related to incretin resistance , drugs that activate epac2 such as glimepiride or glibenclamide may attenuate the deficit incurred by tcf7l2 genotype , whereas a drug like gliclazide might be unable to do so ( figure 1 ) . whether the mentioned differences in the mechanism of action explain it is possible that unknown pathogenetic mechanisms may be involved , and further functional studies are required . , it had limited statistical power to detect small genotype - related differences . because of its exploratory character , in the diabetic patients treated by gliclazide , we observed bigger reduction in hba1c by 0.6% in approximately 50% of patients with the common cc genotype , in comparison with the risk tcf7l2 rs7903146 t - allele carriers . the magnitude of difference may have practical implications ; for example , with the aim to overcome the genetic defect ; the carriers of tcf7l2 t - allele might need higher doses of gliclazide , a sulfonylurea drug with good evidence base and safety profile [ 22 , 23 ] .

previous studies showed associations between variants in tcf7l2 gene and the therapeutic response to sulfonylureas . all sulfonylureas stimulate insulin secretion by the closure of atp - sensitive potassium ( katp ) channel . the aim of the present study was to compare tcf7l2 genotype specific effect of gliclazide binding to katp channel a - site ( group 1 ) with sulfonylureas binding to ab - site ( group 2 ) . a total of 101 patients were treated with sulfonylureas for 6 months as an add - on therapy to the previous metformin treatment . tcf7l2 rs7903146 c / t genotype was identified by real - time pcr with subsequent melting curve analysis . analyses using the dominant genetic model showed significantly higher effect of gliclazide in the cc genotype group in comparison with combined ct + tt genotype group ( 1.32 0.15% versus 0.73 0.11% , padj = 0.005 ) . no significant difference in hba1c between the patients with cc genotype and the t - allele carriers was observed in group 2 . in the multivariate analysis , only the tcf7l2 genotype ( p = 0.006 ) and the baseline hba1c ( p < 0.001 ) were significant predictors of hba1c . after introducing an interaction term between the tcf7l2 genotype and the sulfonylurea type into multivariate model , the interaction became a significant predictor ( p = 0.023 ) of hba1c . the results indicate significantly higher difference in hba1c among the tcf7l2 genotypes in patients treated with gliclazide than in patients treated with glimepiride , glibenclamide , or glipizide .

states are undertaking new program initiatives to deal with the problem of the uninsured . merrill ( 1990 ) describes these initiatives and argues for the necessity of greater public - private sector cooperation and for policy changes at the federal level . these state efforts raise the question of what the role of the federal government should be these issues are discussed in light of our growing body of knowledge about the uninsured and their characteristics . in the last 5 years , health services research has done much to improve our understanding of the nature and extent of the problems with insurance coverage . although there is some controversy about the absolute number of uninsured persons ( stemming from the specifics of survey questions ) , there is general agreement that the number is large on the order of 31 to 37 million at any point in time ( between 13 and 16 percent of the population ) . furthermore , although the number of uninsured and their proportion ( as a percent of the nonelderly population ) rose in the first half of the eighties , since then the percentage has remained more or less constant ( brown , 1989 ) . in addition , four stylized facts about the characteristics of the uninsured have become part of the conventional wisdom that shapes the debate : nearly three - quarters of the uninsured are workers or dependents of workers . about one - third of the uninsured are in families with incomes below the poverty level . one - fourth of the uninsured have incomes greater than three times the poverty level . these facts would seem to argue for a combination of gap - filling measures such as mandating or subsidizing employment - related insurance , expanding the medicaid program , and even direct service programs for school children . the fact that so many uninsured are workers suggests that we should build on our current , largely employment - based system . the fact that only one - third are poor suggests that medicaid expansions alone are unlikely to reach a majority . the fact that so many are young places a greater moral burden on society as a whole . and the fact that many have substantial incomes , far above the poverty level , suggests the difficulty of covering everyone through a gap - filling strategy . though such a strategy could conceivably reach the vast majority of the uninsured , short of a mandate that individuals have insurance , these measures would not necessarily cover every person . through a number of modeling efforts in the last few years , we now have a fairly good notion of the likely impact of such strategies . three principal and important conclusions emerge from this literature : a strategy using a combination of gap - filling measures would cover most of the uninsured . the strategies vary greatly in how the costs would be distributed among individuals , firms , state governments , and the federal government . the net addition to national health spending of these improvements in coverage would not be large in relation to national health spending . a brief summary of key findings from recent major studies follows . in 1988 , the congressional research service ( 1988b ) conducted a study of several combinations of employer - based plans coupled with a medicaid expansion . using the lewin - icf health benefits simulation model ( based in part on 1980 national medical care utilization and expenditure survey data ) , they estimated that a medicaid expansion to cover all of the poor ( defined as those below the poverty level ) would leave 29 million uncovered . although such an expansion would increase medicaid program costs by $ 13.3 billion , it would increase national health spending by only $ 4.1 billion ( if it had been in effect in 1986 ) . if combined with a tailored employer - based plan ( i.e. , emphasizing preventive services and having smaller deductibles ) , the number of uninsured would be reduced from 37 million to 6 million . the resulting increase in national health spending consumer - choice health plan based on a strategy of managed competition among public and private health plans to promote informed , cost - conscious consumer choice . their proposed system would be universal , covering all of the currently uninsured , and it would rely on a combination of mandated employer coverage for full - time workers and subsidies for the poor ( below 150 percent of the poverty level ) and others not covered through employment . according to congressional budget office estimates for 1988 , their expanded employment - related coverage would cover about 22 million of the currently uninsured . new federal expenditures would be approximately $ 12.8 billion , but there would be $ 12.4 billion in new tax revenues . they project a one - time , $ 15 billion increase in national health spending in the first full year of implementation . thorpe , siegel , and dailey ( 1989 ) analyzed the impact of medicaid expansion with a model based on medicaid program data on age - specific program costs . similar to the congressional research service ( crs ) , they found that in 1987 - 88 an expansion to cover all the poor would leave 26.1 million uninsured . net public spending would rise by $ 7.75 billion , and new national health spending would be less than this , though the cost depends on the richness of the package in terms of covered services and the level of provider payments . thorpe ( 1989 ) extended the preceding analysis to examine the impacts of an employer mandate in addition to a medicaid expansion . he found that the various employer mandates could extend coverage to 24.6 million of the 37 million uninsured and could affect the coverage of many other workers , depending on the nature of the mandate . adding medicaid coverage up to the poverty level to this would result in total coverage of more than 30 million of the previously uninsured . and national health spending is projected to increase by only $ 12.5 billion under this combination . also demonstrated in this article are the drastically different distributional impacts of different types of mandates . in recent work for the health care financing administration , lewin - icf , using the same model as in their work for crs , projects that in 1989 a medicaid expansion to cover all the poor plus pregnant women and infants up to 185 percent of the poverty level would leave 24.6 million uninsured ( needleman et al . , 1990 ) . allowing a buy - in to the medicaid program for others between the poverty level and 185 percent of the poverty level would reduce this to 21.3 million uninsured . an employer mandate requiring coverage of full - time and most part - time workers would , alone , leave only 6.2 million uninsured . and if coupled with a medicaid expansion , this could reduce the number of uninsured to 2.7 million . the change in national health spending from various combinations of options would range from $ 11 billion to $ 19 billion , depending on whether provider reimbursement is increased . holohan and zedlewski ( 1989 ) examined a much wider range of medicaid expansion options , ranging up to 200 percent of the poverty level . their simulations use the urban institute 's transfer income model augmented with enrollee cost estimates based on medicaid tape - to - tape data . coverage ( through subsidized medicaid buy - ins , etc . ) would leave 11.3 million uninsured if extended only to those below 200 percent of the poverty level . they find that medicaid program costs could rise substantially ( $ 47.2 billion ) under the highest of these options . however , they do not present an estimate of the change in national health spending . a detailed review of the preceding studies would reveal that the distribution implications of these alternatives vary dramatically and are quite complex . medicaid expansions would place the burden on the federal and state governments ( and ultimately the taxpayers ) , roughly , 60 percent for the federal government and 40 percent for the state . they also tend to reduce other public spending on uncompensated care as well as out - of - pocket spending by the uninsured . the impact of employer mandates depends on assumptions about employee cost - sharing , changes in tax subsidies , and the nature of compensation . in addition , who bears the costs may vary in the short versus long run , particularly because firms may bear substantial costs immediately that are ultimately borne mostly by individuals as part of compensation . also , there may be long - run employment effects ( as the minimum wage is effectively raised ) and impacts on consumers ( if prices rise as a result ) . the results of these simulations also depend on the following assumptions about : the set of services in the benefit package . the treatment of those covered by va / champus . the incentives for some small firms not to participate in some arrangements , in effect pushing their employees to the public plan . differentials in the per unit prices currently paid by different insurers . taken as a whole , these studies suggest that national health spending would increase only between $ 10 and $ 20 billion as a result of combined implementation of these gap - filling measures , which would reach the vast majority of the uninsured . this amount does not seem large in comparison with total national health spending in 1988 of $ 540 billion , which was an increase of $ 51 billion over 1987 . this range of impact on national health spending is corroborated from another perspective , based on use of services by the uninsured . it is suggested from previous studies that the uninsured receive at least 50 percent and , perhaps , up to 70 percent of the amount of care they would receive if insured . this is demonstrated in table 1 , in which a summary of estimates from several studies of the utilization of hospital and physician services by the uninsured is given . also cited in the table is a recent paper by long and rodgers ( 1989 ) in which they review this literature in detail and conduct empirical analyses of data from the survey of income and program participation ( sipp ) , a unique longitudinal data source . their findings indicate that , with appropriate correction for the dynamic nature of insurance status , these estimates of use by the uninsured may be overstated . thus , the 50-percent end of the range may be a better estimate . in any case , within this range , the estimates of the impact of covering the uninsured on national spending are plausible for the following reason . in 1987 , average health spending for persons under 19 years of age ( who were 31 percent of the nonelderly uninsured in 1987 ) averaged $ 745 , and for persons 19 - 64 years , it was $ 1,535 ( waldo et al . , 1989 ) . thus , if the uninsured had received care at these average expense levels , their total expenditures in 1987 would have been $ 47.1 billion . if only 50 percent of this was actually provided , then expanded coverage would result in additional national health expenditures of $ 24 billion . or , if 70 percent is currently provided , then national health expenses would increase by only $ 14 billion . this crude calculation could be adjusted for health status and other factors , but even at this level , it provides a consistency check on the results of the microsimulation models . the bottom line is that the additional spending to cover the uninsured is unlikely to represent more than 5 percent of what national health spending would be otherwise . one limitation of the modeling efforts discussed previously is that they are based on a count of the number of uninsured at a given point , with little consideration given to the dynamic nature of insurance status . nelson and short ( 1989 ) found that over a 28-month period 28 percent of the population was without health insurance for at least 1 month . this is much higher than the 13 - 16 percent at a point in time . they also estimate that only 4 percent of all persons were without coverage for the entire period and another 3 percent had coverage for less than 6 months . second , also using the sipp , monheit and schur ( 1988 ) estimate that over a 32-month period 22 percent of those who began with private insurance lost coverage at some point , if only for a short time . conversely , only 27 percent of those who began the period uninsured remained so the entire period . these important new findings , highlighting the dynamic nature of insurance coverage , imply that current microsimulation models based on point - in - time estimates of the number of uninsured could have serious shortcomings . in particular , this implies that the administrative burden associated with these changes in status is probably large and would be somewhat larger if employer coverage is mandated . it is less clear , however , how accounting for the substantial turnover in the uninsured population should affect estimates of medical care expenses . in their analysis of the sipp data , long and rodgers ( 1989 ) found no evidence that these transitions in status affect the average differential in use between the insured and uninsured . it may well be that the current models provide reasonably accurate medical expenditure estimates but fall short primarily in considering the additional administrative costs . of course , recognition of high rates of turnover in the uninsured population may have important programmatic , social , and political implications , in terms of the viability of reforms . in addition to medicaid expansions , merrill ( 1990 ) places state initiatives into three general categories : employer mandates ( such as play or pay ) , insurance subsidies , and risk pools . although there is much to learn from these state efforts , there is also good reason to believe that they will not adequately address the problem of the uninsured in the near term . at the very least , as merrill notes , effective medicaid expansions will require federal action to decouple the system from welfare status . with regard to the massachusetts play - or - pay plan in particular and state plans in general , enthoven and kronick ( 1989b ) argue that such innovations are unlikely to succeed for three reasons . first , the pre - emption of the employment retirement income security act of 1974 allows firms that are self - insured to operate outside of state control . second , there are potential adverse employment impacts if states with these provisions become less desirable business sites . third , such plans do not take full advantage of the federal tax subsidy to health insurance . yet , these state initiatives may be most informative about our ability to extend coverage , via direct subsidies as well as reinsurance , to the significant numbers of uninsured workers in small businesses . nonetheless , given the substantial variability among states in their medicaid programs , it is difficult to see a way around these problems without , ultimately , the establishment of a broader federal framework . as many have noted , the much heralded cost - containment initiatives of the eighties have done little to slow the growth in national health spending . they may well have shifted more of the cost of care for the uninsured to public hospitals and to the uninsured themselves . although the proportion of the population that is uninsured has not grown in recent years , this persistent problem is perhaps increasingly seen as a national problem , if not a national embarrassment , that must be addressed . a major implication of the results summarized here is that this debate might be improved by an emphasis on the impact on the change in national health spending rather than on program costs or federal outlays . given the federal deficit situation , the usual focus on program costs is understandable . nonetheless , the additional costs to society of providing coverage to the uninsured are probably not as substantial as many would imagine . federal policymakers should be able to take a societal perspective on this issue . in their efforts to forge a workable combination of medicaid reform and other gap - filling measures , which clearly could cover the vast majority of the uninsured at a reasonable cost , these policymakers would be well - served to adopt and to present this broader perspective . in summary , in answer to the questions posed at the outset of this discussion , there is much the federal government can do to improve coverage of the uninsured both directly and indirectly through state initiatives . in particular , decoupling medicaid from welfare status and developing a buy - in option are steps that could lead to coverage of over one - half of the uninsured . helping the remainder ( of mostly working uninsured ) is more difficult through state initiatives alone , though state initiatives may represent our best opportunity for learning what innovations are feasible . the distributional consequences of alternative gap - filling measures vary greatly , which is one of the reasons it has been so difficult to construct a political solution to this problem . although the political attention given to these distributional consequences is understandable , the prospects for a viable solution could be improved if federal policymakers would keep the costs of these initiatives in view from a broader societal perspective .

implications are discussed for federal policy of gap - filling initiatives at the state and federal level to deal with the problem of the uninsured . measures currently under active consideration that involve expansions of medicaid and employment - related insurance are considered in the light of recent studies of the uninsured and recent simulations of their cost and coverage impacts . the limited impact of these gap - filling measures on additional national health spending , in contrast to program costs and federal outlays , is emphasized . placing greater emphasis on this broader societal perspective could assist federal policymakers in developing an acceptable strategy for covering the uninsured .

painful bladder syndrome ( pbs ) is defined as chronic ( over 6 months ) pelvic pain , pressure , or discomfort perceived to be related to the urinary bladder , accompanied by at least one other urinary symptom such as a persistent urge to void or frequency in the absence of an identifiable cause ( van de merwe et al . , 2008 ) . therefore , pbs should be considered when pelvic pain with voiding symptoms of frequency and urinary urgency , or when experiencing recurrent urinary tract infection with urinary tract and pelvic pain . of course , a number of doctors believe that there is no such disease or that it is rare ( warren , 2014 ) ; however , more than 10 million people in the united states who suffer from the above mentioned symptoms are misdiagnosed or have been neglected for years ( dyer and twiss , 2014 ) . in 2006 , research suggested that up to 12% of women in the united states may have early symptoms of pbs , and approximately 400,000 people in the united kingdom suffer from pbs , of whom 90% are females and 10% are males ( nickel et al . , 2010 ) . in korea , the prevalence of pbs is 0.12% , which is lower than that of europe and the united states ( choe et al . , 2011 ) . although it is not a life - threatening disease , the severity of symptoms can be excruciating , so that the decrement of quality of life is greater compared to those treated with hemodialysis for end - stage renal disease . therefore , it is important to pay attention to this disease , not only for the incidence , but also for the severity of symptoms . as urologists , each time we make a diagnosis and decide on treatments for pelvic pain , clear communication between the patient and the doctor is of utmost importance . in general , patients do not share information about previous diagnosis and treatments from previous medical institutions , but rather only their current symptoms at the time of the visit . effective and active communication between medical provider and patient would raise awareness of recurrent urinary tract infection and bladder pain syndrome , based on the erudite knowledge of the diseases . we suggest 6 tips to medical staff and patients for easy diagnosis and proper treatment ( table 1 ) . first , self - awareness of the disease is necessary . when there is pain around the pelvic floor , including pelvis , urethra , and vagina area , along with voiding dysfunction lasting more than 1 month , a pelvic related disease should be considered . although pbs has been known as a female disease , recently , it appears that over a few million men also suffer from it ( hanno et al . , 2011 ) . the most important characteristic in men is that pain comes from not only the lower abdomen , urethra , or lumbar , but also testicles , scrotum , anus , and perineum area ; moreover , a patient might have pre - diagnosed prostatism and prostatitis . second , if the patient has any history of urinary tract infection from repeated prostatitis , cystitis , or vaginitis , but no urine culture test has been performed to check for infection , an immediate urine culture test is required . third , specify the location of pain mentioned above : lower abdomen , urethra , vagina , pelvis , fundus , and so on . pain associated with certain activities such as sexual intercourse or ejaculation may be related to another cause . fourth , if it is not a functional disorder of an overactive bladder with urinary incontinence , frequency , or urgency nor inflammatory disease such as pelvic inflammation or urinary tract infection , pbs should be considered . fifth , when each of the four tips listed above matches the patient s symptoms , stress management , pain management via oral administration , behavior that induces the symptom , and need for dietary control should be well explained . drinking enough water helps in prevention of urine concentration , and consuming alcohol , artificial sweeteners , caffeinated or carbonated drink , citron fruit juice , and spicy cuisine may exacerbate the symptoms ( carinci et al . , 2013 ) . hot or cold pack on the painful area may reduce the pain itself ( chaiken et al . , 1993 ) . last , find an expert before being swamped with negative information on diseases which does not necessarily help in treatment of patients . despite the emergence of modern medicine , positive outcomes to either cure or alleviate the symptoms are still dubious , with some particularly dire side effects or unabated discomfort . while weighing between those side effects and expedient medication interventions , like tamsulosin ( tamsulosin hcl , alpha11-adrenoceptr antagonists ) or elmiron ( sodium pentosan polysulfate ) , and nsaid , and pain killer , doctors could be esoteric with regard to whether or not to continue the medication , or patients themselves could decide not to take medications without consulting beforehand ( parsons et al . , 1994 ) . the medication has neither conquered pelvic pain nor other urinary symptoms ultimately , but along with some physical therapy , beleaguered patients have shown great progress in managing their pain ( chaiken et al . , 1993 ) . there are reports emphasizing the importance of breathing and meditation prior to therapy ( nickel et al . , 2010 ) . the deep breathing engages with the core muscle and learning how to hold the core will strengthen it . consecutively , meditation to overcome mental fatigue resulting from pbs may reduce urinary frequency and urgency as well ( carrico et al . , 2008 ; webster and brennan , 1998 ) . some urologists consider anxiety and stress as the main cause of pbs and other pelvic ( van de merwe et al . , 2008 ; warren , 2014 ) . when there is unprecedented stress , the toxins that form contribute to the discomfort and dysfunction of bladder and urinary problems . in modern times , people practice yoga to learn how to breathe , to meditate , and to relax the muscles . vinyasa yoga ( sun salutation ) appears to be the most efficacious and therapeutic remedy , and there are others that patients can easily follow at home ( uebelacker et al . , 2010 ) . the cat stretching pose in yoga relieves lower abdominal pain , and the hip lift pose strengthens the hip muscle while learning to control holding the core muscle ( fig . hatha yoga , an ancient type of physical and mental exercise , is also a useful modality for releasing the pain with interstitial cystitis ( ripoll and mahowald , 2002 ) . there is a phrase you are what you eat. indeed , the importance of a balanced diet and its consequences to health has become common knowledge . these days , people are armed with diet information pouring from media , books , magazines , and the internet . it is undoubtedly a positive phenomenon that people are now aware and in charge of their own health care . superfoods , like berries and tomatoes , has become popular ( as if we can live just by consuming them ) , are we apprehensive about the fact that some foods , largely known as having health benefits , can trigger and worsen pbs symptoms ? some studies provide a list of foods to avoid worsening and herbs and supplements to consume , and there are quite a few surprises ( nickel et al . , 2010 ) . patients must avoid alcohol , artificial sweets , carbonated drinks , coffee , and tea ( capodice et al . surprisingly , patients must also avoid certain fruits , including citrus , berries , and pineapples , onions , soy sauce , spices , tomatoes , and vinegar . foods with low glycemic index , such as beans , most whole grains , nuts , animal proteins , most vegetables , and legumes are suggested , while dairy is recommended for patients with chronic inflammation . a gluten - free diet would be beneficial to pbs patients with coeliac disease or noncoeliac gluten intolerance ( chao et al . , 2015 ) . the list of recommended herbs and supplements includes : bromelain , buchu , cornsilk , cranberry , d - mannose , fennel seeds , glucosamine sulphate and chondroitin sulphate , gokshura , l - arginine , liquorice , lotus seeds , marshmallow root , prelief , pumpkin seeds , purnanava , quercitin , and sea buckthorn ( capodice et al . , 2005 ; carinci et al . , the case for cranberry is that it is helpful for patients who have a tendency to develop urinary tract infections , but it can make the symptoms even more severe for those with pbs . notice that making one s own cranberry juice is recommended due to the copious amounts of sugar in commercial juices . coconut milk smoothies , cucumber milk , and cilantro smoothies are conducive to alleviating pbs symptoms ( chaiken et al . , 1993 ; parsons and koprowski , 1991 ; shorter et al . , 2007 appropriate diagnosis and treatment of pelvic pain in pbs is still very difficult because of the lack of definitive knowledge about its etiology , pathophysiology , and treatment modality . we present practical tips for easy diagnosis and proper treatment of pelvic pain in pbs . physical and food therapies are alternative treatments for pelvic pain in pbs therapy , instead of medical treatment . fundamentally , we advise that both medical staff and patients be dedicated and committed for achievement of long - term healing .

painful bladder syndrome ( pbs ) is a common disease presenting with chronic pelvic pain and discomfort with at least one urinary symptom with no identifiable cause . the etiology is still unknown , and the medication has limited effects on pelvic pain or other urinary symptoms . this article presents advanced insight regarding the approach to pbs , particularly pelvic pain for primary care practitioners and patients . we suggest six tips for medical staff and suspected patients for easy diagnosis and proper treatment of pelvic pain . these six tips cover : self - awareness of the disease ; immediate urine culture test ; specifying the location of pain urinary incontinence ; frequency , or urgency without functional disorder of an overactive bladder helpful dietary control ; complementary , and alternative medicine , and finding an expert . these tips might be helpful in advancing the schematic approach and in achieving better prognosis of pbs . further study should be conducted to achieve better treatment for this disease , including development of a definitive test and diagnosis .

as a common head and neck cancer , nasopharyngeal carcinomas are generally either keratinizing or nonkeratinizing squamous cell carcinomas . primary nasopharyngeal adenocarcinomas ( npacs ) are rare neoplasms , constituting only 0.38% to 0.48% of all malignant nasopharyngeal neoplasms . thyroid - like low - grade nasopharyngeal papillary adenocarcinoma ( tl - lgnppa ) is a small minority of conventional nasopharyngeal adenocarcinoma that exhibits papillary growth and abnormal expression of thyroid transcription factor 1 ( ttf-1 ) . to the best of our knowledge , only thirteen cases have been reported in the english - language literature and eleven in the chinese - language literature to date ( table 1 ) . in this article , we present a case of primary tl - lgnppa and an analysis of its clinicopathological features . a 15-year - old chinese girl presented with a complaint of rhinorrhoea and nasal congestion with a duration of 1 month . on clinical examination , no thyroid tumor or other physical abnormalities were found . nasal endoscopy identified a pedunculated polypoid mass with smooth surface that measured approximately 2.52 cm arising from the posterior nasal septum ( fig . follow - up data showed no signs of local recurrence at up to 2 years after complete surgical removal . the tissue was fixed in formalin and embedded in paraffin , after which 4-m thin sections were cut and stained with hematoxylin and eosin . immunohistochemical staining was performed using commercially available antibodies to the following antigens : pan - cytokeratin ( ckpan ) , epithelial membrane antigen ( ema ) , vimentin , cytokeratin ( ck ) 7 , cd15 , thyroid transcription factor 1 ( ttf-1 ) , ki-67 , p40 , s100 , glial fibrillary acidic protein ( gfap ) , ck20 , cdx-2 , and thyroglobulin . at the same time , in situ hybridization for the presence of small epstein - barr virus ( ebv)encoded rna was performed to identify the association between this tumor and ebv . histological examination of the biopsy specimen revealed a tumor that showed papillary configuration with hyalinized fibrovascular cores , similar to thyroid papillary carcinoma ( fig . the papillae were complex and tightly packed , and most were lined with cuboidal or columnar epithelia containing overlapping round to ovoid nuclei that displayed fine chromatin and mildly eosinophilic cytoplasm ( fig . 2c ) . small intra - nuclear cytoplasmic inclusions were present focally , although neither nuclear grooving nor ground glass nuclei were found . in small parts of the tumor , no necrosis or mitotic activity was discerned and no continuity between the tumor epithelia and normal nasopharyngeal mucosa or mucous glands was identified . immunoperoxidase studies showed that neoplastic cells were positive for ck7 , vimentin , ttf-1 , ckpan , and ema ( fig . there was no immunoreactivity for thyroglobulin , cd15 , s100 , p40 , ck20 , cdx-2 , and gfap . in the most concentrated spot , npac contains two subtypes : conventional / surface origin - type and salivary gland - type . the latter includes polymorphous low - grade adenocarcinoma , mucoepidermoid adenocarcinoma , and adenoid cystic carcinoma . in 1988 , wenig et al . first described thyroid - like papillary adenocarcinoma of the nasopharynx and proposed that these papillary adenocarcinomas should been regarded as a distinct entity from conventional adenocarcinomas in this region based on their indolent clinical behavior and low - grade histological features . nasopharyngeal papillary adenocarcinoma ( nppa ) was enrolled in the world health organization classification system of malignant epithelial tumors of the nasopharynx in 2005 . papillary configuration and aberrant ttf-1 expression are the distinguishing features of tl - lgnppa , mimicking papillary thyroid carcinoma ( ptc ) . tl - lgnppa is an extremely rare neoplasm . to the best of our knowledge , the median age is 35 years in patients , ranging from 9 to 68 years . instances of tl - lgnppa were usually localized in the roof of the nasopharynx and posterior edge of the nasal septum . the excellent prognosis was obvious , with local excision being performed in all reported cases , and no local recurrence or metastasis reported . histologically , these neoplasms frequently exhibit papillary architecture lined by moderately pleomorphic columnar epithelial cells with fibrovascular cores , overlapping nuclei with clear optically chromatin , and psammoma bodies . however , the biphasic pattern of low - grade nppa with a spindle cell component has been described in three case reports . in this case , no obvious spindle cell component was observed . the biphasic pattern of tl - lgnppa should be further investigated if a large number of cases can be collected . immunohistochemically , the positive expression of ttf-1 was the most characteristic feature of tl - lgnppa . as a homeodomain containing transcription factor coded by nkx2 - 1 , ttf-1 is usually found in lung , thyroid , and central nervous system tissue . nevertheless , the positive expression of ttf-1 was also observed in other organs , including endometrium , colon , and breast . although the etiology of ttf-1 positive staining in tl - lgnppa is still not clear , three mechanisms to explain this phenomenon were proposed in a recent case report . second , a gene rearrangement that affects ttf-1/nkx2 - 1 may result in abnormal expression of ttf-1 . finally , genetic instability and reprogramming of the cancer cells can cause dis - differentiation and lead to deregulation of ttf-1/nkx2 - 1 . however , these presumptions are poorly evidenced owing to the extreme rarity of this tumor at the present time . there are limited options available for differential diagnosis of papillary lesions in the nasopharynx . because tl - lgnppa display a striking resemblance to ptc , it is important to exclude nasopharyngeal metastasis from papillary adenocarcinoma of the thyroid gland for accurate diagnosis , treatment , and prognosis of the patient . immunostaining for thyroglobulin and cd15 are critical and highly recommended to distinguish these two entities . however , a case of tl - lgnppa with focal expression of thyroglobulin was recently reported . polymorphous low - grade papillary adenocarcinoma ( plga ) is more aggressive and positive for vimentin and s100-protein . to date , positivity for ttf-1 has never been reported in plga . papillary variants of the intestinal type of adenocarcinoma ( itac ) show more nuclear atypia and commonly display mucinous differentiation . acinic cell carcinomas ( acc ) with a papillary component are frequently cystic and variably positive for s100-protein and vimentin according to the range of differentiation ( acinar to intercalated ducts ) . extraventricular choroid plexus papillomas ( cpp ) at unusual localization must be taken into consideration , most of them was positive for s100 and negative for ema , part of them was positive for gfap . in our report , negative staining for thyroglobulin , cd15 , s100 , gfap , ck20 , and cdx-2 was revealed ; therefore , ptc , plga , itac , acc , and cpp should not be considered for accurate diagnosis . it has been well documented that tumors originating from the nasopharyngeal epithelium were associated with the ebv . investigation of in situ hybridization for ebv revealed negative results , which is concordant with reports by wu et al . a close relationship between tl - lgnppa and ebv was not confirmed ; however , further investigation is needed because of the rarity of this neoplasm . to date , no case of lymphatic metastasis or recurrence has been reported , indicating excellent prognosis for patients with thyroid - like papillary adenocarcinoma . generally , surgical excision is adequate for the treatment of tl - lgnppa . when surgical excision is not feasible or positive surgical margins have been observed , radiotherapy can be employed as an adjuvant treatment . in conclusion , we present here a novel case of tl - lgnppa with a review of its main clinicopathological features . due to the rarity of this neoplasm and favorable clinical outcome , clinicians should pay more attention to accurate diagnosis of this entity , as well as its treatment and clinical prognosis .

purposeprimary low - grade thyroid - like papillary adenocarcinomas are extremely rare neoplasms that generally originate in the nasopharynx . here , we describe a novel case of a 15-year - old chinese girl who was diagnosed with low - grade thyroid - like papillary adenocarcinoma , including a brief review of the literature to reveal the clinicopathological features of low - grade thyroid - like nasopharyngeal papillary adenocarcinoma.materials and methodsimmunohistochemistry was used to evaluate the expression of pan - cytokeratin ( ckpan ) , cytokeratin ( ck ) 7 , thyroid transcription factor 1 ( ttf-1 ) , vimentin , epithelial membrane antigen ( ema ) , thyroglobulin , cd15 , s100 , p40 , ck20 , cdx-2 , glial fibrillary acidic protein ( gfap ) , and ki-67 . additionally , in situ hybridization investigation was utilized to identify the presence of small epstein - barr virus ( ebv)encoded rna.resultshistopathological analysis revealed florid proliferation of papillary structures lined by columnar epithelial cells with fibrovascular cores . immunohistochemically , the neoplastic cells were positive for ckpan , ck7 , ttf-1 , vimentin , and ema , but negative for thyroglobulin , cd15 , s100 , p40 , ck20 , cdx-2 , and gfap . the ki-67labeling index reached 5% in the most concentrated spot . in situ hybridization for ebv was negative.conclusiondue to the distinct rarity of low - grade thyroid - like papillary adenocarcinomaswith a favorable clinical outcome , a nationwide effort to raise public awareness of this neoplasm is required .

intracranial arachnoid cysts are benign csf filled , congenital , intra - arachnoidal space - occupying lesions that represent 1% of all intracranial lesions . we report an unusual case of a floating fat globule within a multi - compartmental suprasellar arachnoid cyst and discuss its possible etiopathogenesis . a 29-year - old woman presented with a 1-year history of frontal headache not associated with features of raised intracranial pressure . mri of the brain done at the onset of headache revealed a multicompartmental cystic lesion occupying the suprasellar region and extending to both sylvian fissures . the lesion was hypointense on t1w and hyperintense on t2w images and fluid - attenuated inversion - recovery ( flair ) imaging , with no enhancement on gadolinium injection [ figure 1a c and f ] . there was no restriction on diffusion - weighted imaging [ figure 1d and e ] . a focal , well - defined intralesional differential signal intensity , showing t1 shortening and intermediate signal on t2w images , was seen in the right sylvian fissure [ figure 2a and b ] . blooming on susceptibility - weighted imaging ( swi ) and suppression on fat - saturated images suggested the possibility of a fat globule [ figure 2c and d ] . because the patient was not willing for any surgical procedure , she was managed symptomatically . axial t1w mri image ( a ) shows a homogenously hypointense cystic lesion ( arrow ) in the suprasellar cistern , extending posteriorly to the interpeduncular cistern and laterally to both sylvian fissures . it is hyperintense ( arrows ) on t2w ( b ) and flair ( c ) images . the cyst does not show enhancement on a post - contrast t1w image ( f ) axial t1w mri image ( a ) shows a hyperintense intracystic nodule with intermediate signal intensity on a t2w image ( b ) . the hyperintense signal is suppressed completely on t1w fat - saturated spin - echo image ( d ) . the arrows in the images indicate the nodule ten months later , in view of worsening headache , she was re - evaluated by ct scan . noncontrast ct scan revealed an iso - hyperdense lesion in the same location with the fat globule seen ( hypodensity ) in the suprasellar cistern [ figure 3 ] . repeat mri after 1 month showed suppression of the cyst contents on flair imaging [ figure 4c ] and a shift in the position of the intracystic nodule to the left anterior temporal region [ figure 4a and b ] . due to failure to control the headache with medication , the patient was taken up for decompression of the lesion . at surgery , a cerebrospinal fluid ( csf)-containing cyst with a transparent membrane the cyst collapsed on incision , revealing a yellowish , soft globule lying free within it [ figure 5 ] . histopathological examination revealed flattened arachnoid cells lining a fibrocollagenous membrane , consistent with a diagnosis of arachnoid cyst [ figure 6 ] . plain axial ct scans show an iso - hyperdense cystic lesion with suprasellar fat density . note the change in position of the fat globule ( arrow ) axial t1w mri ( a ) and t2w mri ( b ) images show the changed position of the fat globule ( arrow ) , now situated in the left anterior temporal region . coronal flair mri imagte ( c ) shows suppression of the cyst contents ( arrow ) intraoperative photographs demonstrate the arachnoid membrane ( arrow in a ) and the intralesional fat globule ( arrow in b ) photomicrograph shows the cyst wall lined by cuboidal to flattened meningothelial cells ( arrow ) over a layer of fibrocollagenous tissue ( h and e , 400 ) arachnoid cysts are benign , congenital , intra - arachnoidal space - occupying lesions that are filled with clear csf . they tend to be unilocular , smoothly marginated expansile lesions and are molded by the surrounding structures . are found in the middle cranial fossa ; other locations include the suprasellar cistern and posterior fossa ( 10% ) , where they occur most commonly in the cerebellopontine angle cistern . less common locations are within the interhemispheric fissure , over the cerebral convexity , in the cisterna magna , quadrigeminal cistern , and choroidal fissure.[25 ] the precise mechanism for the formation of arachnoid cysts is not known . it is possible that they are secondary to splitting of the developing arachnoid . a newer concept for the middle fossa arachnoid cyst is failure of the temporal embryonic meninges to merge as the sylvian fissure forms . other mechanisms might include active fluid secretion by the cyst wall , slow distention by csf pulsations , or one - way ball - valve flow of csf . although most arachnoid cysts remain stable with advancing age , they can sometimes become symptomatic due to cyst enlargement or hemorrhage . hemorrhage may occur not only in the cyst but also in the subdural or extradural spaces . previous / chronic minor intracystic blood leakage may be responsible for the hyperdensity visualized on ct scan . occasionally , however , hemorrhage , high protein content , or lack of flow within the cyst may complicate the mri appearance . in our patient , there was a change in the mri characteristics of the lesion on repeat imaging , suggesting the possibility of a cystic lesion with varying protein content , e.g. , neuroepithelial cyst , dermoid cyst , or colloid - like cyst . in view of the lack of restriction on diffusion - weighted imaging the presence of a freely mobile globule within the lesion precluded the diagnosis of an arachnoid cyst . the intralesional nodule demonstrated high signal on t1w and intermediate signal on t2w , which was suggestive of fat / cholesterol or proteinaceous material . in view of the suppression on t1w fat - saturated imaging the reason for blooming is not exactly known ; however , exaggerated chemical shift artifact appears less likely , as the hypointensity was not uniform and not at the edges . there have been brief reports recently mentioning hypointensity of fat on swi although the exact reason has not been discussed . microscopically , the arachnoid cyst wall is made up of a vascular collagenous membrane lined by flattened arachnoid cells . rarely , choroid plexus like tissue has been reported in the walls of arachnoid cysts , which supports their maldevelopmental origin.[1113 ] in conclusion , we report the first case of an arachnoid cyst with a mobile fat globule within it . this possibly represents a dual congenital maldevelopment resulting in the formation of an arachnoid cyst and intracranial fat globule .

intralesional floating fat globules have been reported in cystic lesions such as teratoma of the ovary and dermoid of the head and neck but not within intracranial lesions . fat globules dispersed within the subarachnoid space are a known imaging finding of ruptured intracranial dermoid . we report a unique case of an intralesional solitary floating fat globule within a multicompartmental arachnoid cyst , with varying locations on serial imaging . we also put forward a hypothesis for the pathogenesis of fat within an arachnoid cyst . to the best of our knowledge , this is the first such report in the literature .

mycophenolate mofetil ( mmf ) , a commonly used immunosuppressive drug in solid organ transplantation , has resulted in a significant decrease in allograft rejection . mmf is an antimetabolite that inhibits inosine monophosphate dehydrogenase , resulting in blockade of the de novo pathway of purine synthesis . because this pathway is exclusively used by b and t lymphocytes for purine synthesis , mmf administration causes selective inhibition of lymphocyte proliferation . gastrointestinal side effects , including diarrhea , are common with mmf and are caused by specific ( suppression of de novo purine synthesis ) and nonspecific ( immunosuppressive ) effects of the drug on the gastrointestinal tract . mmf - related colitis has many features in common with graft - versus - host disease ( gvhd ) colitis seen in patients who have undergone allogeneic bone marrow transplantation , including crypt architectural disarray , gland distortion with lamina propria fibrosis and edema , increased lamina propria inflammation , and increased crypt epithelial apoptosis . some have also found enterocyte atypia , increased neuroendocrine cells , and microvascular injury . we report a case of colitis with features consistent with both mmf colitis and gvhd in a patient receiving mmf as part of an immunosuppressive regimen after heart transplantation . because the recipient was female and the donor was male , we used fluorescence in situ hybridization ( fish ) for the y chromosome to determine the origin of the lymphocytes present within the colon biopsy . the presence or absence of donor lymphocytes in colonic lesions in conjunction with clinical data could help to determine the cause of the patient 's colitis and guide treatment . the patient was a 69-year - old woman with a past medical history significant for osteopenia , chronic lower back pain and diverticulosis who presented with weakness and fatigue for approximately one month accompanied by low blood pressure ( 70/40 mm hg ) and mild shortness of breath . the patient had a history of a left heart catheterization in 2007 which showed dilated nonischemic cardiomyopathy with an ejection fraction of approximately 30% . on the last admission prior to transplantation , the patient was hypotensive and had an ejection fraction of 15% . she was started on dobutamine , and an implantable cardioverter - defibrillator device was placed . once a heart became available for transplantation , the patient was started on prednisone , mmf , and tacrolimus . the patient 's postoperative course was complicated by an upper extremity deep venous thrombosis for which the patient received enoxaparin 60 mg subcutaneous every 12 h. the patient was discharged to home on postoperative day eight on valgancyclovir , pravastatin , iron sulfate , enoxaparin , nystatin , diltiazem - sr , bactrim - ds , aspirin , lexapro , and an immunosuppressive regimen including tacrolimus 4 mg every 12 h , a prednisone taper , and mmf 750 mg every 12 h. two months after transplantation , the patient presented with a two - week history of watery stools and diarrhea consisting of four to five episodes after each meal with occasional maroon blood in the stool . these episodes were preceded by cramping , nonradiating abdominal pain and were not accompanied by fevers , chills , nausea , vomiting , hematemesis , melena , chest pain , shortness of breath , dizziness , palpitations , dysuria , or hematuria . she had a history of hemorrhoids and diverticulitis in the past and had also had a recent colonoscopy which was negative . microscopic studies of her stool were negative for giardia lamblia , entamoeba histolytica , ova and parasites , salmonella spp . , cryptosporidium , campylobacter spp . , as well as c. difficile toxin and antigen and rotatvirus antigen . an abdominal x - ray demonstrated no intestinal obstruction . a colonoscopy performed at this time showed severe diverticulosis , and biopsies revealed colonic mucosa with crypt apoptosis , lamina propria fibrosis , and inflammatory cell infiltrate which could be consistent with gvhd it was felt that the patient 's symptoms , including bleeding and bloating , were due to mmf , and her immunosuppressive regimen was change to tacrolimus and azathioprine with amelioration of her gastrointestinal symptoms . fish for the x and y chromosome was performed on paraffin - embedded tissue prepared in the histology lab at thomas jefferson university hospital . the slides were subjected to deparaffinization using hemo - d ( three washes , 10 min each ) and 100% ethanol ( two washes , 5 min each ) . the slides were pretreated as follows : 0.2 n hcl for 20 min at room temperature followed by a wash in 2 ssc for 3 min at room temperature ; 2 ssc at 73c for 30 min ; 30% pepsin in 2 ssc for 30 min at 45c followed by a wash in 2 ssc for 3 min at room temperature ; proteinase k for 20 min at 45c followed by a wash in 2 ssc for 3 min at room temperature . the slides were postfixed in 10% formalin for 10 min at room temperature and washed in 2 ssc for 3 min at room temperature . the slides were dehydrated and denatured and prepared for hybridization with cep x and cep y dual color probe ( 1:10 dilution ) ( vysis , des plaines , ill . the slides were washed in posthybridization buffer for 2 min at 72c and counterstained with 4(,6-diamidino-2-phenylindole . microscopic examination of the random colon biopsies revealed colonic mucosa with areas of crypt apoptosis and lamina propria fibrosis ( fig . 1 ) . there was a mixed inflammatory cell infiltrate predominately composed of mature lymphocytes . no viral inclusions were identified , and a special immunohistochemcial stain for cytomegalovirus was negative ( data not shown ) . because the patient was female and the donor was male , fish was performed to detect the presence of the y chromosome in lymphocytes present in the biopsy material . gender - mismatched transplantations , in which a female patient receives a male donor organ , offer a unique opportunity to investigate recipient tissues , because the detection of the y chromosome discriminates the cells of donor origin from recipient - derived cells . no y chromosome signals were detected , indicating there was no significant infiltrate by cells derived from the male heart donor ( fig . mmf , a commonly used immunosuppressive drug for solid organ transplantation , has resulted in a dramatic decrease in graft rejection . mmf acts by inhibiting inosine monophosphate dehydrogenase resulting in selective inhibition of the de novo pathway for purine synthesis . purine synthesis can occur via the de novo and/or the salvage pathway in most cells . however , lymphocytes are unique in that they almost exclusively use the de novo pathway . these effects are due to specific and nonspecific effects of mmf on the gastrointestinal tract . one nonspecific effect is increased immunosuppression leading to increased susceptibility of the gastrointestinal mucosa to infection by microorganisms and viruses . increased immunosuppression does not increase susceptibility to any single organism but results in more likely infection with less pathogenic organisms as well as increased symptomatology in cases where infections may have remained subclinical . because enterocytes have a high turnover rate , inhibition of proliferation by mmf can have a dramatic effect on mucosal integrity . interestingly , after administration , the highest concentrations of mmf have been found in the gastrointestinal tract , which may exacerbate the effect of mmf on these cells . there is some evidence that in lymphocytes , with increasing exposure to mmf there is induction of inosine monophosphate dehydrogenase expression which may counteract the effects of mmf . some feel that this may also occur in enterocytes which may explain the decrease in additional incidence of gastrointestinal side effects after 6 months of mmf usage . there has been limited examination of the histologic findings associated with mmf - related colitis with several groups reporting gvhd - like histology . in one study , mmf colitis showed a significant difference in crypt cell apoptosis , gland distortion , epithelial cell atypia , the number of neuroendocrine cells , and lamina propria inflammation as compared to matched controls . a later study demonstrated that despite the overlap in histologic features , certain findings such as crypt cell apoptosis and the number of apoptotic cells were increased with gvhd as compared to mmf exposure . this study also found that mucosal architectural disarray , epithelial cell atypia , lamina propria inflammation , number of intraepithelial lymphocytes , number of neuroendocrine cells , mononuclear cell apoptosis , and microvascular injury were also increased in both patients with gvhd and those exposed to mmf as compared to controls . a recent study showed that in patients exposed to mmf , gvhd - like histology can be seen throughout the gastrointestinal tract including the stomach and esophagus . some may argue that the histologic findings that some are attributing to mmf toxicity may actually be due to gvhd . as opposed to bone marrow transplantation , gvhd is uncommon in solid organ transplantation . billingham suggested that three criteria must be met in order for gvhd to occur : ( 1 ) presence of hla differences between the host and donor , ( 2 ) presence of immunocompetent donor cells , and ( 3 ) suppression of the host immune system . these criteria are easily met in bone marrow transplants that are not hla - matched since a competent immune system is transplanted along with other marrow elements necessary for effective hematopoiesis . in solid organ transplantation , a small number of immunocompetent cells are present in transplanted organs . also , due to logistical concerns , the organs are often not hla - matched . some solid organs carry more lymphoid tissue , which explains the larger number of reported cases of gvhd in liver , small bowel , and heart - lung as opposed to kidney and heart transplantations . the presence of donor lymphocytes has been documented in recipient tissue using hla antibodies and short tandem repeat analysis . the presence of these lymphocytes has correlated with the presence of gvhd in these recipients . in the current case , infectious etiologies were ruled out , and a colon biopsy demonstrated findings consistent with grade 1 gvhd . because the recipient was female and the donor was male , we were able to determine the origin of lymphocytes present within the colon biopsy using a probe for the y chromosome . we decided against using short tandem repeat analysis , which is commonly employed for bone marrow engraftment studies , because the colon biopsy was paraffin - embedded , which would have reduced our ability to adequately amplify dna present within the biopsy . examination of the peripheral blood for donor lymphocytes was not performed due to the unavailability of this specimen at the time of our study . ultimately , we showed that there was no significant donor lymphocyte infiltrate in the recipient colon biopsy . this finding together with the improvement of the patient 's symptoms subsequent to removal of mmf from the patient 's immunosuppressive regimen suggest that mmf toxicity , as opposed to gvhd , was the cause of the patient 's colitis . although the patient was also administered steroids subsequent to the colon biopsy for possible gvhd , we feel that given the lack of donor lymphocytes in the colon biopsy , the rapid improvement in symptoms subsequent to mmf withdrawal , and the rarity of gvhd in heart transplantation , mmf toxicity is a much more likely cause of the patient 's symptomatology . in the current case , we found that there is substantial overlap between the histologic findings present in gvhd and mmf - related colitis . molecular techniques , including fish where appropriate , can be employed to demonstrate the presence or absence of donor lymphocytes . molecular findings properly correlated with clinical and morphologic findings can help direct therapy which may include withdrawal of the offending agent , in the case of mmf - related colitis , or administration of steroids , in the case of gvhd .

mycophenolate mofetil ( cellcept ) , a commonly used immunosuppressive drug in solid organ transplantation , has recently been shown to cause graft - versus - host disease ( gvhd)-like changes in the gastrointestinal tract . on rare occasions , true gvhd has also been documented in the gastrointestinal tract of solid organ transplant patients . because the treatment for these two entities is different , i.e. removal of the offending agent versus the administration of steroids , proper identification of the cause is imperative . we present a case of mycophenolate mofetil colitis mimicking grade i gvhd of the gut . in our study , we used fluorescence in situ hybridization for the y chromosome to document the lack of male donor lymphocytes in the female recipient colon biopsy . we suggest that molecular techniques including fluorescence in situ hybridization could be used to discriminate between mmf - related colitis and true gvhd in order to help guide therapy .

decubital ischemic fasciitis is a rare entity occurring mostly in the elderly and in debilitated patients , in the deep subcutaneous tissue , at pressure points or bony prominences.[14 ] it can simulate a soft - tissue sarcoma clinically and histopathologically.[14 ] imaging helps to rule out malignancies and therefore to prevent unnecessary interventions . a 72-year - old woman presented with a palpable mass over the right hip region . physical examination revealed a 4- to 5-cm , hard , and fixated mass in the right proximal thigh , located posterolateral to the greater trochanter . mri revealed diffuse hyperintense signals on the t2w images [ figures 1a and 1b ] consistent with edema and inflammation , in the muscles and subcutaneous tissues , with prominent , peripheral , and ill - defined enhancement [ figure 2 ] , over an area measuring approximately 4 - 7 cm , at the level of the greater trochanter . a ct - guided needle biopsy showed coagulative necrosis , hemorrhage , and fibrosis involving the adipose tissue . the capillary and muscular vessels within the lesion also showed fibrinoid necrosis in their walls , without evidence of primary vasculitis [ figure 3 ] . these findings , along with the clinical features , were considered compatible with the diagnosis of ischemic fasciitis ( atypical decubital fibroplasia ) . axial ( a ) and coronal ( b ) fat - suppressed t2w images show diffuse hyperintense signals ( arrows ) in the muscles and subcutaneous tissues , adjacent to the right greater trochanter axial contrast - enhanced t1w , fat - suppressed mri shows subtle , peripheral enhancement ( arrow ) in an area measuring approximately 47 cm , at the level of the greater trochanter histopathologic slide ( h and e stain ) shows coagulative necrosis and hemorrhage with capillary and muscular vessels showing fibrinoid necrosis in their walls ( arrows ) decubital ischemic fasciitis , also called atypical decubital fibroplasia , is a distinctive fibroplasia occurring predominantly in the elderly and debilitated patients , confined to bed or wheelchair - bound.[13 ] the lesions occur in the deep subcutaneous tissue at pressure points or bony prominences . it is a rare condition , and 40 cases have been reported in the literature until 2009 . ilaslan et al . have reported the mri features of decubital ischemic fasciitis in three patients . on mri , the mass - like area in our patient was isointense compared to muscle on the t1w images , and hyperintense on the t2w images . after administration of gadolinium , subtle and peripheral enhancement was seen in the subcutaneous and muscular tissues . the bone adjacent to the affected soft tissue ( greater trochanter ) was not involved . lesions occurring in the shoulder , sacral area , posterior chest wall , and vulvovagina have been reported . the diagnosis of decubital ischemic fasciitis with typical findings on mri prevents the already debilitated patient from undergoing further and unnecessary interventions . consideration of this entity by the clinician and the radiologist helps the pathologist rule out malignancy . we want to point out that since mri is a common and appropriate imaging method used to examine soft - tissue masses , all radiologists , especially those evaluating musculoskeletal mri examinations , should be aware of this entity and be familiar with the clinical features , common locations , and mri findings .

the mri findings in a case of decubital ischemic fasciitis located posterolateral to the right greater trochanter , in a 72-year - old woman , are presented . decubital ischemic fasciitis is an uncommon entity encountered mostly in debilitated , elderly patients , in the deep subcutaneous tissue , at pressure points or bony prominences . it can simulate soft - tissue sarcomas . recognition of this lesion radiologically is important to prevent unnecessary interventions .

solid cell nests ( scns ) of the thyroid have fascinated pathologists since they were first described by getzowa in 1907 . although it is now widely accepted that scns and so - called mixed follicles are indeed ultimobranchial body remnants [ 28 ] , their biological significance remains controversial [ 24 , 9 , 10 ] . it has been suggested that these embryonic remnants may be the origin of certain ectopic structures rarely reported in thyroid glands [ 3 , 6 ] and also of certain types of thyroid tumor [ 9 , 10 ] . moreover , scns may be a source of confusion in thyroid pathology , as they can mimic a number of pathological disorders [ 2 , 3 ] . thyroglossal duct cysts , lingual thyroid remnants , and scns are believed to harbor pluripotent stem cells [ 2 , 3 , 7 ] . solid cell nests are composed of two cell types : main cells and c cells . main cells , which account for a major proportion of scns , are polygonal - to - elongated cells with centrally located , oval nuclei ; they have uneven nuclear envelopes and occasionally display strongly eosinophilic cytoplasm with squamoid features ( including high molecular weight cytokeratins ) but lack intercellular bridges . the minority c cells are characterized by clear cytoplasm and small , compact , centrally located nuclei [ 24 ] . in up to 81% of cases , mixed follicles may be found admixed with bona fide scns [ 24 ] ; these are composed of cells resembling main cells and differentiated follicular cells arranged in a follicular lumen - like pattern . it has been suggested that main cells might be pluripotent cells contributing to the histogenesis of c cells and follicular cells , as well as to some thyroid tumors [ 11 , 12 ] , but little research has addressed this hypothesis . if this were the case , main cells might be expected to display a stem cell phenotype , with the capacity both to self - renew and to generate differentiated progeny , as well as the ability to exist in a mitotically quiescent form , although these properties are not always present in all human tissue stem cells . the present study sought to analyze and characterize thyroid differentiation markers ( p63 , bcl-2 , cytokeratin 19 , galectin-3 , ttf-1 , thyroglobulin , calcitonin ) and also stem cell markers ( oct4 and sall4 ) in scns found in nodular hyperplasia . formalin - fixed paraffin - embedded tissue sections from ten scn - containing surgical specimens obtained during total thyroidectomy were retrieved from the files of the hospital infanta luisa ( seville , spain ) . patient age , sex , functional status , and underlying scn - associated thyroid disease are summarized in table 1 . the study was approved by the hospital ethical committee and informed consent was obtained from all participants . table 1summary of the patient 's clinicopathological features and immunostaining findings in solid cell nestscasea / st3 , t4 , tshpdmain cellsc cellsp63bcl-2ck19gal-3tgttf-1*ctp63bcl-2ck19gal-3tgttf-1ct164/fwnlnh++++-+++245/mwnlnh+++++++343/fwnlnh+++++++436/fwnlnh+++++++570/fwnlnh+++++++637/fwnlnh+++++++744/mwnlnh+++++++869/fwnlnh+++++++962/fwnlnh+++++++1046/fwnlnh+++++++wnl within normal limits , pd pathological diagnosis , a age ( years)/s sex ( f female , m male ) , * 30 % of main cells shown positive immunoreactions , ck 19 cytokeratin 19 , gal-3 galectin-3 , ttf-1 thyroid transcription factor , tg thyroglobulin , ct calcitonin summary of the patient 's clinicopathological features and immunostaining findings in solid cell nests wnl within normal limits , pd pathological diagnosis , a age ( years)/s sex ( f female , m male ) , * 30 % of main cells shown positive immunoreactions , ck 19 cytokeratin 19 , gal-3 galectin-3 , ttf-1 thyroid transcription factor , tg thyroglobulin , ct calcitonin for immunohistochemical analysis , 4 m serial sections were stained with a panel of antibodies ( table 2 ) using the streptavidin biotin negative ( primary antibody replaced by non - immune mouse serum ) and positive controls were included in each slide run . a minimum of 10% positive staining was adopted as a cut - off for all markers . for p63 and ttf-1 , only nuclear staining was considered specific , while for other markers , only cytoplasmic staining was accepted . table 2antibodies used for immunohistochemical analysisantigenantibodydilutioncalcitoninpolyclonal ( biogenex , san ramon ca)1:5,000ttf-18g7g3/1 ( dako , glustrup , denmark)1:2,000thyroglobulindak - tg6 ( dako , glustrup , denmark)1:2,000ck 19rck108 ( dako , glustrup , denmark)1:100p634a4 ( dako , glustrup , denmark)1:50bcl-2124 ( dako , glustrup , denmark)1:20galectin-39c4 ( dako , glustrup , denmark)1:200ttf-1 thyroid transcription factor-1 , ck 19 cytokeratin 19 antibodies used for immunohistochemical analysis ttf-1 thyroid transcription factor-1 , ck 19 cytokeratin 19 all tissue sections contained scns which are composed of a complex admixture of main cells and c cells , as previously described ( fig . intermingled with main cells , and mainly confined to the periphery of cell nests , c cells were numerically less conspicuous and were characterized by clear or empty cytoplasm and round nuclei . in six cases ( 60% ) , structures lined by main cells and follicular epithelium with colloid and/or clumps of eosinophilic material in the lumen ( fig . a. solid cell nest composed of a complex admixture of main and c - cell ( x 20 ) . b. cystic scns . mixed follicles composed of cells resembling scn main cells and cuboidal cells arranged in a follicle - like structure ( h / e , 40 ) solid cell nests of the human thyroid . a. solid cell nest composed of a complex admixture of main and c - cell ( x 20 ) . b. cystic scns . mixed follicles composed of cells resembling scn main cells and cuboidal cells arranged in a follicle - like structure ( h / e , 40 ) positive staining for p63 was restricted to scn main cells ( fig . main cells in all tissue sections displayed strong nuclear staining for bcl-2 , while staining was negative in c cells ( fig . positive staining for ck19 was observed consistently in main cells , as well in follicular cells of mixed and some adjacent follicles ( fig . both main cells and c cells showed strong nuclear and cytoplasmic staining for gal-3 ( fig . e , f tg and pth , negative staining in both main and c cells ( 40 ) . h ttf-1 , moderate nuclear staining in a small number of scn cells , mainly those forming mixed follicles ( 40 ) immunohistochemical analysis . e , f tg and pth , negative staining in both main and c cells ( 40 ) . h ttf-1 , moderate nuclear staining in a small number of scn cells , mainly those forming mixed follicles ( 40 ) tg is considered the most specific marker of thyroid follicular differentiation . here , none of the scns stained positive for tg ( fig . ct staining was detected in c cells of all scns and in parafollicular cells of adjacent thyroid tissue ( fig . positive staining for ttf-1 was detected in all differentiated cells of the thyroid parenchyma and in a few scn cells , mainly those forming mixed follicles ( fig . positive staining for pth was not detected either in scns or in surrounding thyroid tissue ( fig . only two cases showed granular cytoplasmic staining to be negative in all cases for sall4 . solid cell nests may pose a challenge to the thyroid specialist , since they may be confused with squamous metaplasia , metastatic squamous carcinoma , papillary microcarcinoma , medullary carcinoma , and c cell hyperplasia c [ 2 , 3 ] . it has been assumed that a histological evaluation based on the typical immunohistochemical profile of scns ( cea and cytokeratins ) should be sufficient to distinguish them from their mimics [ 2 , 3 ] . however , since cea and cytokeratins are also coexpressed in some neuroendocrine carcinomas [ 10 , 14 ] , other more specific markers are required . as reported by other authors , expression of gal-3 in the present study positive staining for p63 was detected in scn main cells but not in surrounding thyroid tissue . other authors report similar findings [ 11 , 12 , 16 ] , adding that p63 is not expressed in certain differentiated carcinomas ( medullary and follicular ) [ 12 , 17 ] and indeed is only exceptionally expressed in foci of squamous metaplasia in papillary carcinomas . thus , p63 may prove a highly effective marker for distinguishing scns from other pathologies . although there is no precise definition of stem cells , it is generally understood that they exhibit the capacity both to self - renew and to generate differentiated progeny , as well as the ability to exist in a mitotically quiescent form , although these properties are not always present in all human tissue stem cells . p63 is a structural homolog belonging to the p53 tumor suppressor family involved in the survival and differentiation of stem cells in various epithelia [ 19 , 20 ] . it has been suggested that p63 may trigger the differentiation of certain specific cell lines [ 1921 ] . in addition , strong bcl-2 expression was detected here in main cells ; this is characteristic of a non - committed embryonic phenotype associated with stem cells . main cells stained negative for two differentiation markers , pth and tg ; this allowed scns to be distinguished from parathyroid tissue remnants and suggested the absence of main cell differentiation towards tg - producing follicular cells . however , positive staining for ct was occasionally detected in scn cells which resembled parafollicular cells in surrounding thyroid tissue , suggesting an intra - scn differentation of this cell line . positive staining for ttf-1 was detected in some peripheral scn cells ; to judge by the findings of other authors , these were probably c cells . positive ttf-1 staining was also noted in mixed follicle cells and in all follicles in surrounding thyroid tissue . the hypothesis regarding the embryonic nature of scns is borne out by the fact that ttf-1an early marker of thyroid cell differentiation [ 23 , 24]was not expressed by most scn cells ( undifferentiated cells ) . the putative stem cell role of scns is further supported by the continuity observed between main cells , mixed follicles , and follicular and parafollicular cells . this strongly suggests that , as reported by other authors , scn main cells may be pluripotent cells contributing to the histogenesis of c cells and follicular cells as well as to some thyroid tumors . this hypothesis is borne out by the immunohistochemical profile of scns obtained in the present study and by the findings of other authors who report a marked capacity for self - renewal ( telomerase activity ) a and low proliferation index in these cells . until now , scns have been seen solely as a morphological feature of thyroid tissue ; a number of hypotheses have been put forward regarding their nature and their purpose . the results of the present study using stem cell markers failed to confirm the initial hypothesis , since oct4 protein expression whose significance is uncertain was detected in only two cases , and sall4 expression in none . future research should thus focus on other specific stem cell markers ( e.g. , nanog , sox2 ) . as part of the general quest to identify specific stem cell populations in a range of organs and tissues in both healthy and sick patients [ 25 , 26 ] , a number of authors have postulated a stem cell role for scns in the thyroid gland ; some studies have even linked them to the genesis of several tumors , including papillary , mucoepidermoid , and squamous carcinoma [ 10 , 11 , 27 ] . attempts have also been made to demonstrate the presence the same braf mutation ( v600e ) in scns and in micropapillary carcinoma . there appears to be no evidence to support the link between scns and medullary carcinoma posited by a several authors [ 4 , 28 ] . the literature , accordingly , contains contradictory views on the potential link between stem cells , scns ad thyroid carcinoma ; however , all these views are based on immunohistochemical profiles which fail to include absolutely specific stem cell markers [ 29 , 30 ] . the present results contribute to a better knowledge of the nature of scns and may help clarify the genesis of thyroid tumors ; however , they provide no indication of potential therapeutic strategies other than surgery , which for the time being remains the only option . further research is required to determine the relationship between main cells and certain thyroid carcinomas , particularly papillary thyroid carcinoma , whose cells like scn cells display strong positive staining for ck 19 .

it is widely held that solid cell nests ( scn ) of the thyroid are ultimobranchial body remnants . scns are composed of main cells and c cells . it has been suggested that main cells might be pluripotent cells contributing to the histogenesis of c cells and follicular cells , as well as to the formation of certain thyroid tumors . the present study sought to analyze the immunohistochemical profile of scn and to investigate the potential stem cell role of scn main cells . tissue sections from ten cases of nodular hyperplasia ( non - tumor goiter ) with scns were retrieved from the files of the hospital infanta luisa ( seville , spain ) . parathormone ( pth ) , calcitonin ( ct ) , thyroglobulin ( tg ) , thyroid transcription factor ( ttf-1 ) , galectin 3 ( gal3 ) , cytokeratin 19 ( ck 19 ) , p63 , bcl-2 , oct4 , and sall4 expression were evaluated by immunohistochemistry . patient clinical data were collected , and tissue sections were stained with hematoxylin eosin for histological examination . most cells stained negative for pth , ct , tg , and ttf-1 . some cells staining positive for ttf-1 and ct required discussion . however , bcl-2 , p63 , gal3 , and ck 19 protein expression was detected in main cells . oct4 protein expression was detected in only two cases , and sall4 expression in none . positive staining for bcl-2 and p63 , and negative staining for pth , ct , and tg in scn main cells are both consistent with the widely accepted minimalist definition of stem cells , thus supporting the hypothesis that they may play a stem cell role in the thyroid gland , although further research will be required into stem cell markers . furthermore , p63 and gal-3 staining provides a much more sensitive means of detecting scns than staining for carcinoembryonic antigen , calcitonin , or other markers ; this may help to distinguish scns from their mimics .

it is usually due to congenital dysplasia , trauma , strain , or other causes of abnormalities in the bony connection between adjacent vertebrae , leading to partial or complete slippage of one vertebrae on adjacent vertebrae . the typical symptoms of this condition are neurological deficits , including low back pain , nerve root irritation , and neural dysfunctions . a variety of surgical fusion techniques , such as anterior interbody fusion , posterior interbody fusion , posterolateral fusion , repair of the pars interarticularis , and reduction and fusion have been applied to stabilize the spine , relieve pain , and improve the patients life quality . radiological investigation is the key component of evaluation of lumbar spondylolisthesis to determine its anatomical abnormalities , etiologies , severity , and possible pathogenic mechanisms to guide the clinical management and assess the prognosis . for this purpose , a number of x - ray , ct , and mri techniques have been employed to analyze anatomy of vertebrae , lumbar lordosis ( ll ) , and the facet joints associated with the occurrence of slippage . in contrast to the abundant radiological data on spondylolisthesis of single vertebral bodies , data for consecutive lumbar spondylolisthesis are absent , although multilevel lumbar spondylolisthesis does occur and accounts for up to 11% of spondylolisthesis . importantly , multilevel segmental involvement is of considerable significance for the occurrence of cauda equina syndrome . we identified a correlation between the forward displacement of the involved vertebrae and pelvic sagittal parameters . our findings suggest that pelvic compensatory mechanisms play a role in maintaining the overall sagittal spinal and pelvic stability . a total of 967 patients were diagnosed with and treated for spondylolisthesis at our hospital from june 2005 to march 2012 . among them , 17 consecutive spondylolisthesis cases ( 1.75% ) were identified in 5 males and 12 females with a median age of 56 years . out of these 17 patients , 7 had spondylolisthesis involving l3l4 , and 10 had spondylolisthesis involving l4l5 . the enrollment criteria for these patients were as follows : no spinal fractures , or scoliosis history ; no history of spinal surgery ; diagnosis of consecutive spondylolisthesis on a lateral lumbar spine x - ray . the lateral x - ray images for individual patients were retrieved from our picture archiving and communication systems ( pacs ) . the taillard index was defined as the relative displacement distance between the involved vertebrae divided by the horizontal length of the upper vertebral body ( fig . the pelvic incidence ( pi ) was denoted as the angle between the vertical line of s1 endplate and the line connecting midpoint of s1 endplate to midpoint of the femoral heads . the sacrum slope ( ss ) was defined as the angle between the s1 endplate and the horizontal line , while the pelvic tilt ( pt ) was the angle formed by the vertical line and the line connecting the midpoint of s1 endplate to the midpoint of the femoral heads ( fig . the displacement between the upper and lower intervertebral space was determined on flexion extension dynamic x - ray radiographs ( fig . 3 ) . the measurement of taillard index : the forward displacement distance of upper vertebral body / the length of the upper vertebral body 100% . the measurement of the lumbar lordosis ( ll ) , pelvic incidence ( pi ) , pelvic tilt ( pt ) , and sacrum slope ( ss ) . the angular displacement of the upper intervertebral space was calculated as ( a1b1 ) ; the angular displacement of lower intervertebral space was determined by calculating ( a2b2 ) . student t test was used to analyze the relative anterior displacement of the vertebrae and the angular displacement of the intervertebral spaces . pearson correlation analysis was applied to investigate the correlation between ll and pelvic sagittal parameters and the correlation between taillard index and angular displacements . this study was approved by the ethical committee of the third hospital of hebei medical university , shijiazhuang , hebei , china . a total of 967 patients were diagnosed with and treated for spondylolisthesis at our hospital from june 2005 to march 2012 . among them , 17 consecutive spondylolisthesis cases ( 1.75% ) were identified in 5 males and 12 females with a median age of 56 years . out of these 17 patients , 7 had spondylolisthesis involving l3l4 , and 10 had spondylolisthesis involving l4l5 . the enrollment criteria for these patients were as follows : no spinal fractures , or scoliosis history ; no history of spinal surgery ; diagnosis of consecutive spondylolisthesis on a lateral lumbar spine x - ray . the lateral x - ray images for individual patients were retrieved from our picture archiving and communication systems ( pacs ) . the taillard index was defined as the relative displacement distance between the involved vertebrae divided by the horizontal length of the upper vertebral body ( fig . 1 ) . the ll was the angle between the l1 endplate and s1 endplate . the pelvic incidence ( pi ) was denoted as the angle between the vertical line of s1 endplate and the line connecting midpoint of s1 endplate to midpoint of the femoral heads . the sacrum slope ( ss ) was defined as the angle between the s1 endplate and the horizontal line , while the pelvic tilt ( pt ) was the angle formed by the vertical line and the line connecting the midpoint of s1 endplate to the midpoint of the femoral heads ( fig . the displacement between the upper and lower intervertebral space was determined on flexion extension dynamic x - ray radiographs ( fig . 3 ) . the measurement of taillard index : the forward displacement distance of upper vertebral body / the length of the upper vertebral body 100% . the measurement of the lumbar lordosis ( ll ) , pelvic incidence ( pi ) , pelvic tilt ( pt ) , and sacrum slope ( ss ) . the angular displacement of the upper intervertebral space was calculated as ( a1b1 ) ; the angular displacement of lower intervertebral space was determined by calculating ( a2b2 ) . the data were analyzed with spss13.0 . student t test was used to analyze the relative anterior displacement of the vertebrae and the angular displacement of the intervertebral spaces . pearson correlation analysis was applied to investigate the correlation between ll and pelvic sagittal parameters and the correlation between taillard index and angular displacements . this study was approved by the ethical committee of the third hospital of hebei medical university , shijiazhuang , hebei , china . twenty isthmic ( upper and lower vertebrae ) and 14 ( upper and lower vertebrae ) degenerative consecutive spondylolisthesis were identified in 34 vertebral bodies in 17 patients ( table 1 ) . among the above mentioned 7 patients with l3l4 consecutive spondylolisthesis . out of the 10 patients with consecutive spondylolisthesis , the average taillard index of the upper vertebrae was 17.6 4.1% , whereas its value for the lower vertebrae was 22.4 4.1% ( t = 7.672 , p the average angular displacement of the upper vertebrae was 10.8 2.6 , whereas that of the lower vertebrae was 18.6 5.5 ( t = 5.251 , p < 0.001 ) . in the 17 patients , the average ll was 58.1 4.3 , the average pi 68.7 4.8 , the average ss 37.2 3.8 , and the average pt 31.6 4.0. a correlation between ll and pi and pt was identified , while pi was correlated with pt and ss ( table 2 ) . in contrast , no correlation was present between taillard index and the angular displacement ( p > 0.05 ) . for example , isthmus crack spondylolisthesis can be due to a congenital isthmus defect , an acute lumbar trauma leading to an isthmus fracture , stress - related fractures caused by chronic fatigue on the basis of congenital isthmus dysplasia . this condition is commonly detected in the 5th lumbar vertebral body in 30- to 40-year - old adults , as males and females are affected approximately equally . on the other hand , degenerative spondylolisthesis is usually secondary to intervertebral disc degeneration and commonly affects l4l5 in 50- to 60-year - old women . although the diverse causative factors usually lead to single - level spondylolisthesis , we found that consecutive spondylolisthesis is not a rare condition , especially in individuals performing long - term heavy physical labor , such as the subjects enrolled in the present study . we also discovered that pelvic compensation mechanisms play a key role in maintaining the overall sagittal spinal and pelvic stability in this condition . to the best of our knowledge , due to its distinct anatomical nature , isthmic spondylolisthesis is considered to be inherently more instable than degenerative spondylolisthesis , a fact reflected by the difference in the angular displacement existing between these 2 types . in the present study , identical types of spondylolisthesis in the 2 levels of vertebrae were present in each individual . therefore , we believe that the effects exerted by the type of spondylolisthesis on angle displacement were minimal in the studied patients . interbody gravity force is transmitted and divided into a compression force perpendicular to the shift force that is parallel to the vertebral endplates . in general , lower vertebral bodies bear greater shearing forces with respect to the upper vertebrae , which can accelerate intervertebral degeneration in the disc and facet joints . consequently , from an anatomical standpoint , the range of movement in the discs that are closer to the lumbosacral region is greater than that in those located away from the lumbosacral region . in line with this mechanism , we found that the angular displacement in the lower vertebral bodies was much more prominent than that in the upper vertebrae in the clinical setting of consecutive spondylolisthesis . it is worth noting that the antishearing force mechanisms are compromised in lumbar spondylolisthesis . to compensate for this defect , a series of compensatory changes these adaptive changes are usually reflected by the alteration of spine pelvis sagittal parameters , such as pi . a number of studies have shown that the extent of increase of pi values in patients with single - level lumbar spondylolisthesis is positively correlated with the severity of displacement of the involved vertebrae . barrey et al has further suggested that pi value is to some extent predictive for displacement of affected vertebrae in 1-level spondylolisthesis . we calculated the pi values in 2-level spondylolisthesis and found that the average pi value in consecutive spondylolisthesis was higher than the reported ones in single - level segment spondylolisthesis ( 68.7 vs 66.3 ) , and not surprisingly either , higher than that in healthy individuals . we postulated that the high pi values in consecutive spondylolisthesis might be a risk factor for displacement of the affected vertebrae . nevertheless , to evaluate the biomechanical relevance of an increased pi value in spondylolisthesis requires further prospective studies . any change in orientation within an anatomical spine segment will cause adaptive changes in adjacent segments in order to maintain the stability of the body . for example , vialle et al have reported that ss values in single - vertebral lumbar spondylolisthesis gradually increase along with the degree of displacement in spondylolisthesis grade i although our results clearly demonstrated that consecutive spondylolisthesis resulted in a modification of pelvic parameters , our data indicated that the values of ss ( 37.2 ) and pt ( 31.6 ) in patients with consecutive spondylolisthesis were higher than those observed in the healthy population ( pt = 25.1 and ss = 30.7 ) in the same age group . in the present study , all the taillard indexes were below 50% , classifying the grade of spondylolisthesis as i or ii . we hypothesize , that the compensatory mechanisms in the spine pelvis sequence in 2-segment spondylolisthesis might be different from that in 1-level spondylolisthesis . another set of data supporting this notion was the failure of identification of the existence of a significant correlation between pt and ss , which was compatible with the reported finding indicating that pi = ss + pt , and there are opposite trend shifts of pt and ss in spondylolisthesis . first , consecutive spondylolisthesis may cause a distinct pelvic spine compensation which leads to a discordant change in pt and ss . second , the small sample size and selection bias in the present study might have led to the occurrence of this discrepancy . as a limitation of the current investigation , we have to point out that the data collected in the present study are derived from x - ray images only . since whole - spine imaging was not employed , we were unable to conduct an analysis of the whole - spine sequence . in summary , our study showed that in the spondylolisthesis of 2 adjacent lumbar segments both the degree of the vertebral slip and the angular displacement of the lower vertebrae were greater , than those of the upper vertebrae , indicating that the compensatory mechanism of the pelvis plays an important role in maintaining the sagittal balance .

abstractradiographic features of consecutive lumbar spondylolisthesis were retrospectively analyzed in a total of 17 patients treated for this condition at the third hospital of hebei medical university from june 2005 to march 2012.to investigate the radiographic features , pelvic compensatory mechanisms , and possible underlying etiologies of consecutive lumbar spondylolisthesis.to the best of our knowledge , there is no previous report concerning the characteristics of consecutive lumbar spondylolisthesis.the taillard index and the lumbar lordosis ( ll ) , pelvic incidence ( pi ) , sacrum slope ( ss ) , and pelvic tilt ( pt ) were determined on lateral x - ray images , and the angular displacement was analyzed on flexion extension x - ray images . correlation between ll and various pelvic parameters and correlation between taillard index and angular displacement were assessed by pearson correlation analysis.a total of 20 cases of isthmic spondylolisthesis and 14 of degenerative spondylolisthesis were retrospectively studied in 17 patients . the taillard index and the angular displacement in the lower vertebrae were both larger than those in the upper vertebrae . statistical analysis revealed that ll was correlated with pi and pt , whereas pi was correlated with pt and ss . however , no correlation was identified between taillard index and angular displacement.in consecutive lumbar spondylolisthesis , the degree of vertebral slip and the angular displacement of the lower vertebrae were both greater than those of the upper vertebrae , indicating that the compensatory mechanism of the pelvis plays an important role in maintaining sagittal balance .

as described in detail below , we first estimated the exposure - response relationship between observed daily mortality and temperature data in manhattan . we then obtained downscaled future temperature projections from sixteen climate models and two greenhouse gas emissions scenarios for manhattan . these two inputs were combined to estimate future mortality related to future temperatures , which were compared to temperature - related mortality in a climatalogical baseline period . we separately accounted for cold - season and warm - season mortality , and also computed net annual changes . historical data on daily deaths covering the 1982 1999 period for manhattan were obtained from the us national center for health statistics ( nchs ) . daily death counts for all internal causes ( icd-9 codes 0799.9 for 19821998 and icd-10 codes a00-r99 for 1999 ) were pooled , excluding accidental causes . we chose this definition for consistency with previous studies ; however this would tend to underestimate heat - related mortality since heat stroke is an daily tmax data were obtained from the national climatic data center for 1982 to 1999 at the central park station . a statistical model ( see supplemental equation 1 ) was developed using poisson general linear regression with log daily non - accidental death counts as the outcome variable and the following predictors : a spline function of daily tmax with 3 degrees of freedom , a natural spline of time with 7 degrees of freedom per year , and a day of week indicator variable . this approach was similar to that used to study temperature for 11 eastern us communities . sensitivity analyses investigated potential confounding by ozone , pm10 , dewpoint temperature and influenza epidemics . future temperature projections were developed using downscaled outputs from 16 global scale general circulation models ( gcms ) used in the intergovernmental panel on climate change fourth assessment report , in conjunction with two future greenhouse gas emissions scenarios . the approach uses monthly bias - corrected and spatially disaggregated ( bcsd ) climate projections at 1/8 degree resolution derived from the wcrp cmip3 multi - model dataset . the output from the land - based grid box corresponding to central park , ny was used to create change factors for each calendar month based on the difference between each 30-year future time slice and the same gcms 30-year baseline time slice . these change factors are then applied to the daily central park weather data to create a future projection with the same statistical characteristics and sequence as the observations . the approach described here does not explore how changes in intra - annual and inter - annual temperature variability may change , for several reasons . additionally , the new york city weather station used in this study does not show a significant trend in the variance of either daily summer maximum temperatures or winter minimum temperatures . further , in an analysis of daily projections for the nyc gridbox from three gcms , horton et al . showed that neither summer tmax nor winter tmin showed significant changes in variance through 2080 . by not considering sub - monthly changes in variability , we were able to use fine spatial resolution projections ( as the 1/8 degree bcsd product is monthly , not daily ) and analyze the entire 21 century ( whereas using daily data would have constrained the analysis to the 2046 - 2065 and 20812100 timeslices for which only a subset ( 9 ) of the gcms are available from the pcmdi data portal ) . note that by applying the delta method separately for each calendar month , we do capture one component of possible changes in intra - annual variance , changes in the annual temperature cycle . this methodology yielded a set of 32 synthetic future temperature projections for daily tmax from 2010 to 2100 based on the three 30 year time slices , and for a baseline period 19701999 . greenhouse gas emissions scenarios represent specific blends of demographic , social , economic , technological and environmental assumptions . we selected 2 scenarios , a2 and b1 , which represent relatively high and low greenhouse gas growth projections , respectively . the a2 scenario assumes relatively rapid population growth and limited sharing of technological change , which combine to produce high greenhouse gas levels by the end of this century , with emissions growing throughout the entire century . the b1 scenario assumes a high level of environmental and social consciousness , which leads to sustainable development , low population growth , high economic and technological advancement , and low energy use . projected mortality impacts were estimated using modeled daily tmax . for any day with tmax greater than 71f , the change in mortality was calculated relative to the minimum mortality temperature for the heat effect , i.e. 59 f . for any day with tmax less than 63f , the change in mortality was calculated relative to the minimum mortality temperature for the cold effect , i.e. 72 f . for days with tmax from 63f to 71f daily additional deaths were computed as ( 1)mortality = y0ercpop where : mortality is daily temperature - related additional deathsy0 is baseline daily mortality rate ( per 100,000 population)pop is county populationerc is percentage change in mortality for a specified change in temperature , derived from the statistical analysis of observed data as described above . mortality is daily temperature - related additional deaths y0 is baseline daily mortality rate ( per 100,000 population ) pop is county population erc is percentage change in mortality for a specified change in temperature , derived from the statistical analysis of observed data as described above . we computed temperature - related daily deaths in this way for each time period ( 1980s , 2020s , 2050s , 2080s ) , and then computed the average number of temperature - related deaths per year ( figure 2 ) . we also computed percent changes in annual average deaths from the 1980s to future time periods ( table 1 ) . the population of manhattan was based on data obtained from the us census 2000 survey , and was held constant throughout the projection period . baseline mortality rates for all ages , which excluded deaths attributable to external causes , were obtained from the u.s . centers for disease control and prevention .

global average temperatures have been rising for the past half - century , and the warming trend has accelerated in recent decades1 . further warming is expected over the next few decades , with significant regional variations . these warming trends will likely result in more frequent , intense and persistent periods of hot temperatures in summer , and generally higher temperatures in winter . daily death counts in cities increase markedly when temperatures reach levels that are very high relative to what is normal in a given location24 . relatively cold temperatures also appear to carry risk2,4 . rising temperatures may result in more heat - related mortality but may also reduce cold - related mortality , and the net impact on annual mortality remains uncertain . here we use 16 downscaled global climate models and two emissions scenarios to estimate current and future seasonal patterns in temperature - related mortality in manhattan , new york . all 32 projections yielded warm season increases and cold season decreases in temperature - related mortality , with positive net annual temperature - related deaths in all cases . monthly analyses showed that the largest percentage increases may occur in may and september . these results suggest that , over a range of models and scenarios of future greenhouse gas emissions , increases in heat - related mortality could outweigh reductions in cold - related mortality , with shifting seasonal patterns .

most commonly , contractures arise where adequate burn care and delivery have not occurred and scar management has not been instigated in a vigorous manner . repair by regeneration can no longer occur when the depth of injury extends beneath the reticular dermis , and healing by secondary intention.1 the resultant wound contraction can lead to contractures over flexor surfaces and its surroundings . for example , limitation of opening jaws may cause difficulties in accessing the dentitions and tissues of the oral cavity , and in using full size of removable denture for the patients . telescopic implant - supported removable partial prosthesis with milled abutments has been used for the patient with burn contracture to provide enough retention and stability for the prosthesis . a 60-year old woman was referred from the plastic surgery department to the department of prosthodontics at yonsei university health system . she had a chief complaint of restoring her oral function and esthetics after series of plastic skin graft procedure done . during the extra oral examination it was noted that the elasticity of muscle and skin tissue around oral angular area was lost due to scars from burns and tissue grafting , which resulted in limited maximum mouth opening of 20 mm . therefore , proper prosthodontic treatment was impossible on the right quadrants of the mouth ( fig . the intraoral examination showed that all of maxillary teeth were missing except tooth number # 25 and splinted gold crowns on # 34 and # 35 , whereas fixed partial denture on # 33 to # 43 were present on the mandible . in order to restore the patient 's masticatory function , prosthodontic treatment plan of using 4 implants on the left quadrants each of two implants were placed on upper and lower posterior left jaws , however no implant on anterior ridge were possible due to severe atrophy of the maxilla . anterior cantilever type removable partial denture was planned to meet patient 's esthetic demand , which consists of a telescopic crown abutment on # 25 and two implant supported abutments on area of # 26 and # 27 in the maxillary area ( fig . 2 ) . on the mandible , implant - supported fixed partial denture on area of # 36 and # 37 was planned . the implants ( strauman basel , switzerland ) ( 4.810 mm ) were placed on predetermined area accompanied with sinus lift ridge augmentation procedure and proper follow up was performed during the 6 month healing period of time . customized abutments were fabricated on implants and designed in the predetermined angle paralleling to the prepared tooth of # 25 ( fig . 3 ) . removable partial denture was inserted to verify phonetics , esthetics and function . key and keyway rigid attachment was used for retention and ledge type rest was used for support ( fig . no complications have occurred in 5 years since the insertion of the prostheses ( fig . removable type of prosthesis was selected as treatment option after considering the factors of oral hygiene maintenance and lip support of patient to improve esthetics . because there was only one natural tooth in the maxilla , we , therefore , had to improve the unfavorable removable partial denture using implants.2 due to the lack of anterior ridge , the implant option on anterior ridge was deemed unavailable , and natural tooth was splinted with implant to support anterior cantilevered prosthesis . combining implants with natural teeth is controversial because of the variations in movement during function.3 a lot of complications regarding implant and tooth - supported prosthesis may arise ; including fracture of the prosthetic components , intrusion of the natural tooth , marginal bone loss , and loss of osseointegration,4 but survival rates of implant and tooth - supported fixed prostheses are comparable to implant - supported fixed prostheses.5 there was no prosthetic complication in implant - and tooth - supported fixed prosthesis in this case . in this case , forces in the cantilevered area were transmitted to the abutments , causing tilting and rotational movements,6 but cantilevered prostheses are preferable when reduced stress is inherent.6,7 the prosthesis in this patient is expected to have a good prognosis since it is designed with hypoocclusion in anterior areas .

the scars and contracture around the oral - facial region may cause difficulty in prosthodontic treatment to restore esthetics and function for the patients , who suffered severe burns . this article presents a technique that uses a fixed partial denture prepared with a conventional milling technique and an attachment to support anterior cantilever removable partial denture , thereby providing a more esthetically acceptable and functional result .

root canal therapy of immature teeth poses a special challenge for the clinician . due to absence of apical constriction or apical stop , it is difficult to limit the obturation process within the root canal space . apexification ( a method including long term application of calcium hydroxide to induce apical closure ) , has several disadvantages . susceptibility to fracture , coronal microleakage and aesthetic concerns during this extended treatment period are additional negative points . placement of artificial apical barriers has been considered as an alternative to traditional calcium hydroxide apexification . the material has been widely employed as artificial apical barrier is mineral trioxide aggregate ( mta ) . mta can be placed in one visit , and induce hard tissue formation.[810 ] it is biocompatible,[1114 ] and has good sealing and antimicrobial properties.[1416 ] although , mta has poor handling characteristics and a long setting time . calcium - enriched mixture ( cem ) cement has been developed with clinical applications similar to those of mta . mta and cem cement showed similar favorable biologic responses in repair of furcal perforation , pulp cap and pulpotomy treatment . cem cement has appropriate handling characteristics and exhibited similar sealing properties to mta when used as root - end filling material . compared the response of periradicular tissues to mta and cem cement as root - end fillings and concluded that cem cement and mta were associated with regenerative periapical tissue response when used as root - end filling biomaterials . usually , one or two visits of calcium hydroxide therapy are performed before application of apical barrier , in order to disinfect the root canal system of teeth with nonvital pulps . however , complete removal of calcium hydroxide from the dentinal walls is reportedly impossible . the purpose of this study was to evaluate the effects of residual calcium hydroxide on the marginal adaptation of the cem apical barrier . the teeth were clinically examined to be free of caries , cracks , restoration , and calcification . the teeth were placed in 5.25% sodium hypochlorite ( naocl ) for 5 h. thereafter , they were rinsed and stored in saline solution . clinical crowns were removed from the cement - enamel junction with a high - speed diamond bur ( d and z germany ) under excess water to create a standardized root length of 14 mm . the root canals were instrumented using k - files ( dentsply maillefer , tulsa , usa ) up to master apical file # 45 and gates - glidden drills 14 ( dentsply , maillefer , tulsa , ok ) in a step back manner . then the access opening was sealed with coltozol ( coltene , altstatten , switzerland ) and sulfuric acid was used to produce apical resorption . briefly , the roots were drowned in melted rose wax ( cavex holland , netherlands ) up to 3 mm from the anatomic apex . after that , the teeth were rinsed with a saline solution , the wax was removed with a scalpel ( supa , tehran , iran ) , and temporary filling was removed from the access opening . the teeth were randomly divided into two experimental groups ( n = 20 ) . in medicated group ( n = 20 ) , calcium hydroxide ( pure calcium hydroxide mixed with distilled water ) ( cina bartar , tehran , iran ) was placed in root canals using a lentulo spiral ( moyco union brach , york , pa ) and a radiograph was taken to ensure complete coverage of the canal . after 1 week , the medicament was removed using 0.5% naocl irrigation and stainless steel hand files ( dentsply , maillefer , tulsa , usa ) . in non - medicated group the cem cement was mixed according to the manufacturer 's instructions and using mta carrier , cem cement was placed in the root canals . this process was continued until 4 mm apical plugs were formed at the root apices . the roots were sectioned perpendicular to its long axis at 5 mm of the anatomic root apex using a high - speed diamond saw ( d and z germany ) . the specimens were mounted on aluminum stubs , sputter - coated with gold and assessed from the top at a 300 magnification under scanning electron microscopy ( vega ii xmu , tescan , czech republic ) . marginal adaptation evaluated at the root apices only , and width of largest gap ( maximum distance between cem cement and surrounding dentin ) in each specimen was scored and recorded [ figures 1a and b ] . a gap between the calcium - enriched mixture cement plug and dentinal wall at the root end can be observed in the ( a ) medicated group ( with prior calcium hydroxide dressing and the ( b ) non - medicated group ( without prior calcium hydroxide dressing ) the kolmogorof - smirnov test was used to confirm normal distribution of the data . the results were analyzed by t - test , and significance level was set at = 0.05 . the scanning electron microscope ( sem ) observation of root ends revealed gaps between cem cement and the dentinal walls in all cases . the average gap width in medicated and non - medicated groups was 158/1 67.1 m and 147/1 34/8 m , respectively . several studies have shown that mta has good marginal adaptation in comparison of other root - end filling materials and the gap size is smaller in mta root - end filled teeth.[2832 ] marginal adaptation of cem cement has not been evaluated . the mean gap size in premedicated and non - premedicated root canals was 158.1 m and 147.1 m , respectively . ( 2.68 m ) , bidar , et al . ( 14.8 m ) and xavier , et al . ( 1.051 and 0.812 m ) in evaluation of marginal adaptation of mta . first , in these studies , mta was placed retrogradely in the root canals and the root - end and marginal adaptation were assessed but in the present study , cem cement was placed in root canals orthogradely ( as an apical plug ) . second , the method of measuring the gaps is different ; torabinejad , et al . and bidar , et al . used longitudinally sections to measure gap widths between mta and the root canal walls . xavier , et al . used transverse sections to evaluate the marginal adaptation of mta as a root - end filling material . here , the gaps between cem cement and the root canal walls at the root apices was evaluated , without performing sectioning at the cem cement and dentinal wall interface . finally , in this study sulfuric acid was used to produce open apex teeth . sulfuric acid resorbs the root apex in a disordered manner , producing irregularities at the root end that may hinder adaptation of cem cement to the dentinal walls and thereby increase the gap size . the size of gaps in this study is comparable with those was observed for marginal adaptation of mta by same method ( 70.2 m and 130.0 m in premedicated and non - premedicated root canals , respectively ) . the present study showed that medication with calcium hydroxide had no adverse effect on marginal adaptation of the cem cement plug . hachmeister , et al . also found that calcium hydroxide therapy for one week did not affect the sealing ability of mta in 70 days . porkaew , et al . found decreased dye leakage in canals obturated with gutta - percha following premedication with calcium hydroxide . bidar , et al . also found that premedication with calcium hydroxide improved marginal adaptation of mta . according to the results of this study , calcium hydroxide medication had no effect on the marginal adaptation of cem cement as an apical plug . because the apical plug technique eliminates the lengthy apexification procedure , in vivo studies focused on the success rate of cem cement apical plug are warranted .

background : this study was to evaluate the effects of calcium hydroxide premedication on the marginal adaptation of the calcium - enriched mixture ( cem ) cement as an apical plug.materials and methods : in this in vitro study , forty single rooted teeth were prepared and apical portion of the roots were immersed in sulfuric acid to produce open apices . the teeth were divided into 2 experimental groups . in medicated group , calcium hydroxide was placed in all canals for 1 week and in non - medicated group no dressing was used . then , a 4-mm apical plug of cem cement was placed in canals ; each root was prepared for observation using scanning electron microscope and the maximum distance between cem cement and surrounding dentin was measured . the data were analyzed by t - test , and significance level was set at = 0.05.results:the mean width of gap in medicated and non - medicated groups was 158/1 m and 147/1 m , respectively . there was no significant difference between the two groups ( p > 0.05).conclusion : calcium hydroxide premedication had no adverse effect on the marginal adaptation of cem cement apical plug .

sepsis affects more than 750,000 patients each year in the united states ; it is the 10th leading cause of death and one of the leading causes for admission to the intensive care unit [ 1 - 4 ] . the estimated mortality from sepsis is 2030% , meaning that approximately 500,000 patients survive their septic episode annually in the united states alone . are they able to resume their lives and regular activities , or does sepsis have far - reaching effects that extend beyond the hospitalization ? ten years ago , quartin and colleagues were the first to show that sepsis has long - lasting effects and increases the risk of death up to 5 years after hospitalization for the septic episode . mounting evidence has since demonstrated that survivors of sepsis have a higher long - term risk of death and a lower health - related quality of life ( hrqol ) when compared with the general population [ 6 - 8 ] . in 2001 , recombinant human activated protein c ( rhapc ) was shown to significantly reduce the 28-day mortality in patients with severe sepsis . a subgroup analysis demonstrated that patients who were more severely ill , with multiple organ dysfunction or with acute physiology and chronic health evaluation ( apache ) ii scores 25 , accrued the greatest benefit from rhapc , resulting in drug approval focused on these sepsis populations . a subsequent randomized controlled trial that evaluated rhapc use in patients with severe sepsis and a low risk of death ( apache ii score < 25 ) found no survival benefit with rhapc . given the high cost of rhapc , the attendant bleeding risk associated with its use , and the lack of clinical trials confirming its efficacy , there continues to be debate and controversy regarding its appropriate use . with the increasing emphasis on patient - centered outcomes in clinical trials , we are now more frequently assessing short - term and long - term survival and , at least sometimes , hrqol . in assessing long - term outcomes among sepsis survivors from the original rhapc trial , the short - term survival benefit for more severely ill patients ( apache ii scores 25 ) treated with rhapc was also evident at 3 , 6 and 12 months , while there was no difference in survival for those less severely ill patients . in the previous issue of critical care , longo and colleagues evaluated the effect of rhapc on long - term hrqol and resource utilization in patients with severe sepsis . using an observational cohort of 100 patients with severe sepsis ( 36 patients received rhapc and 64 patients received standard care ) who survived to day 28 , the patients ' hrqol was measured using the short form 36 ( sf-36 ) at 3 , 5 and 7 months , and resource utilization was measured using patients ' self - reports recorded in a diary . patients who were treated with rhapc had significantly better physical component scores on the sf-36 throughout the follow - up period , without significant differences in other components of the sf-36 . patients treated with rhapc also had a significantly shorter hospital stay compared with patients in the standard care group , and showed statistically nonsignificant improvements in the rate of return to employment . one of the major limitations of their study is that rhapc was administered in a nonrandomized fashion , meaning the use of rhapc was left to the discretion of the attending physician . unfortunately , we are given little information about what factors the attending physicians considered when deciding to treat patients with rhapc . without the design of a randomized controlled trial , the results are subject to bias and confounding by unmeasured factors . the authors recognize these limitations and demonstrated that the two groups of patients ( rhapc vs. standard care ) were similar in illness severity ( apache ii score ) and had similar numbers of comorbidities . however , patients who received rhapc were significantly younger and more likely to have been admitted through the emergency department . further , there are no data provided about other factors that may have influenced survival and hrqol such as the type or severity of comorbities ( hiv , malignancy ) [ 13 - 15 ] , organ dysfunction , use of vasopressors or need for mechanical ventilation . these unmeasured differences may fully or partially account for the observed differences in long - term hrqol . for example , younger patients with minor comorbidities ( for example , hypertension ) and a better chance of long - term survival may have been more likely to receive rhapc than an elderly patient with metastatic cancer . other limitations include the small sample size and the limited power to detect smaller but meaningful differences in other components of the sf-36 or resource utilization . despite the limitations of the study , longo and colleagues address an important issue evaluating the long - term effects of a sepsis therapy . their findings suggest that treatment with rhapc may result in improved long - term physical functioning in patients with severe sepsis . the authors hypothesize that rhapc may reduce acute organ dysfunction , thereby diminishing the likelihood of chronic dysfunction and thus improving long - term hrqol . as noted by the authors , this study does not provide conclusive evidence that rhapc improves long - term hrqol , and nor does this study provide any insight into the mechanisms responsible for the improvement in physical functioning . instead , the study offers intriguing preliminary data that should provide the foundation for a larger , more rigorously designed clinical trial examining the long - term effects of rhapc on hrqol . certainly , if rhapc is shown to improve long - term health outcomes , including hrqol , it will open new windows for drug evaluation and provide more evidence to help us determine the optimal use of this controversial medication . apache = acute physiology and chronic health evaluation ; hrqol = health - related quality of life ; rhapc = recombinant human activated protein c ; sf-36 = short form 36 .

sepsis is one of the most common conditions encountered in the intensive care unit and is the 10th leading cause of death overall in the united states . both long - term survival and health - related quality of life are reduced in survivors of sepsis , yet there is little knowledge of the effect of sepsis - specific interventions on either long - term survival or health - related quality of life . the present article discusses the importance of studying health - related quality of life as it relates to sepsis management strategies , particularly in the context of pharmacologic therapy with recombinant human activated protein c.

small cell lung cancer ( sclc ) has a poor prognosis because of its rapid growth rate and early metastatic dissemination . in general , systemic chemotherapy , with or without radiotherapy , has been recommended as the appropriate therapy , and surgery has had only a limited role . pulmonary resection has been used as part of a combination therapy or for residual lesions following concurrent chemoradiotherapy ( ccrt ) . pulmonary resection has also been used for mixed type lesions with non - small cell lung cancer ( nsclc ) . there have only been a few reports regarding surgical outcomes in patients with sclc [ 6 - 9 ] . we investigated the outcomes and risk factors of surgery in the patients from a single institution who underwent major pulmonary resection for sclc within the past 20 years . a total of 3,194 patients underwent major pulmonary resection for malignant neoplasm at our institution from april 1990 to december 2009 . the pulmonary resections were performed via a posterolateral thoracotomy ( n=31 ) or video - assisted thoracoscopic surgery ( vats ) ( n=3 ) . mediastinal lymph node dissections were routinely performed , and all patients who had any component of sclc seen on histology were included in this study . the kaplan - meier analysis was used to plot the survival curves and the rates of freedom from recurrence as well as to compare the survival rates between stage i and ii , and stage iii disease . univariate cox regression analyses were used for risk factor analysis of death or disease recurrence . the seventh edition of the american joint committee on cancer ( ajcc ) cancer staging was used for the stage classification . there were 28 males ( 82.4% ) and six females ( 17.6% ) , and the mean age was 64 years ( range , 44 to 76 years ) . lobectomy was performed in 24 patients ( 70.6% ) , and pneumonectomy was performed in 8 patients ( 23.5% ) . a segmentectomy and bilobectomy were both performed in one patient ( 2.9% ) ( table 1 ) . this patient died of sudden cardiac arrest , and the cause of shock was thought to be bleeding at the pneumonectomy site . pure sclc was confirmed in 24 patients ( 70.6% ) , and mixed type tumors with nsclc was confirmed in 10 patients ( 29.4% ) on the postoperative histological examination . squamous cell lung cancer was most often accompanied by a mixed histology ( n=4 , 11.8% ) . twenty - six patients had pathologic stage i or ii disease , and eight patients had stage iii disease ( table 1 ) . ten patients ( 29.4% ) received ccrt , and one patient ( 2.9% ) received only chemotherapy . adjuvant therapy was not performed in three patients because of either their poor general condition or other complications ( table 2 ) . the median follow - up period was 26 months ( range , 4 to 241 months ) . there were eight late deaths ( 26.5% ) during the follow - up period ; four died of disease progression and the other four died of pneumonia or another non - cancerous cause . the cancer recurred in six cases ( 17.6% ) , which were all systemic recurrences ( table 3 ) . in this study , 1 ) and the three - year disease - free survival rate was 79.2% ( fig . the three - year survival rate according to the pathologic stage was 84% in patients with stage i and ii disease and 13% in patients with stage iii disease ( p=0.001 ) ( fig . the risk factors for death or disease recurrence were analyzed using the univariate cox - regression hazard model . as the number of the deaths and patients with disease recurrence was too small for statistical analysis , we analyzed the risk factors for death or disease recurrence . lymph node metastasis ( p=0.001 ) and the absence of adjuvant chemotherapy ( p=0.008 ) were shown to be risk factors for death or recurrence ( table 4 ) . there were 28 males ( 82.4% ) and six females ( 17.6% ) , and the mean age was 64 years ( range , 44 to 76 years ) . lobectomy was performed in 24 patients ( 70.6% ) , and pneumonectomy was performed in 8 patients ( 23.5% ) . a segmentectomy and bilobectomy were both performed in one patient ( 2.9% ) ( table 1 ) . this patient died of sudden cardiac arrest , and the cause of shock was thought to be bleeding at the pneumonectomy site . pure sclc was confirmed in 24 patients ( 70.6% ) , and mixed type tumors with nsclc was confirmed in 10 patients ( 29.4% ) on the postoperative histological examination . squamous cell lung cancer was most often accompanied by a mixed histology ( n=4 , 11.8% ) . twenty - six patients had pathologic stage i or ii disease , and eight patients had stage iii disease ( table 1 ) . ten patients ( 29.4% ) received ccrt , and one patient ( 2.9% ) received only chemotherapy . adjuvant therapy was not performed in three patients because of either their poor general condition or other complications ( table 2 ) . the median follow - up period was 26 months ( range , 4 to 241 months ) . there were eight late deaths ( 26.5% ) during the follow - up period ; four died of disease progression and the other four died of pneumonia or another non - cancerous cause . the cancer recurred in six cases ( 17.6% ) , which were all systemic recurrences ( table 3 ) . in this study , the overall five - year survival rate was 66.4% ( fig . 1 ) and the three - year disease - free survival rate was 79.2% ( fig . the three - year survival rate according to the pathologic stage was 84% in patients with stage i and ii disease and 13% in patients with stage iii disease ( p=0.001 ) ( fig . the risk factors for death or disease recurrence were analyzed using the univariate cox - regression hazard model . as the number of the deaths and patients with disease recurrence was too small for statistical analysis , we analyzed the risk factors for death or disease recurrence . lymph node metastasis ( p=0.001 ) and the absence of adjuvant chemotherapy ( p=0.008 ) were shown to be risk factors for death or recurrence ( table 4 ) . in general , the role of surgery in sclc is limited as sclc is usually treated using chemotherapy or ccrt . the important role of chemotherapy in sclc has been well - established by clinical trials . despite the development of new chemotherapeutic agents for decades , sclc remains a disease with a high mortality rate and a low cure rate , even in limited stage groups . despite their initial responses to therapy , most patients with sclc develop local recurrence . there have been some previous reports regarding the role of surgery and its outcome in patients with sclc . shah et al . reported that the five - year survival rate was 43% when treated with only surgery in 28 patients with sclc . schreiber et al . indicated that the use of surgery , particularly lobectomy , was associated with favorable survival outcomes . there were other reports regarding the surgical outcome using adjuvant therapies [ 1,15 - 17 ] . in these reports , in the majority of cases , the use of surgery as part of multimodality therapy had more successful outcomes than those of conventional therapies . as seen in previous reports , current ccrt protocols have demonstrated local failure rates of approximately 50% . complete surgical resection after induction ccrt has shown control of local relapse in almost 100% . this was particularly noticeable in the early stage groups ( t1 - 2 , n0 , m0 ) . in our study , 84% of the stage i and ii group and 13% of the stage iii group patients showed a three - year survival rate . histologically mixed tumors with both sclc and nsclc components may fail to meet ccrt protocol requirements since there is less sensitivity of the nsclc component to chemotherapy . it has been shown that the final histological findings for tumors that were initially reported as sclc indicated that they contained nsclc components in 11% to 25% of patients . in our study , lymph node metastasis and the absence of adjuvant chemotherapy were risk factors for patient death or tumor recurrence . it was a retrospective investigation with only a small number of subjects . despite these factors , according to our study results , major pulmonary resection for sclc was feasible in selected patients . prospective , randomized studies will be needed to determine the role of surgery in early - stage sclc .

backgroundthe experience of a single - institution regarding surgery for small cell lung cancer ( sclc ) was reviewed to evaluate the surgical outcomes and prognoses.materials and methodsfrom july 1990 to december 2009 , thirty - four patients ( 28 male ) underwent major pulmonary resection and lymph node dissection for sclc . lobectomy was performed in 24 patients , pneumonectomy in eight , bilobectomy in one , and segmentectomy in one . surgical complications , mortality , the disease - free survival ( dfs ) rate , and the overall survival rate were analyzed retrospectively.resultsthe median follow - up period was 26 months ( range , 4 to 241 months ) , and there was one surgical mortality ( 2.9% ) . six patients ( 17.6% ) experienced recurrence , all of which were systemic . eight patients died during follow - up ; four died of disease progression and the other four died of pneumonia or of another non - cancerous cause . the three - year dfs rate was 79.22.6% and the overall survival rate was 66.410.5% . recurrence or death was significantly prevalent in the patients with lymph node metastasis ( p=0.001 ) as well as in those who did not undergo adjuvant chemotherapy ( p=0.008 ) . the three - year survival rate was significantly greater in the patients with pathologic stage i / ii cancer than in those with stage iii cancer ( 84% vs. 13% , p=0.001).conclusionmajor pulmonary resection for small cell lung cancer is feasible in selected patients . patients with pathologic stage i or ii disease showed an excellent survival rate after surgery and adjuvant treatment . prospective randomized studies will be needed to define the role of surgery in early - stage small cell lung cancer .

nutrient profiling classifies individual food products according to their nutrient content . in the 1924/2006 european regulation , nutrient profiling is proposed as a tool for deciding whether a given food might be eligible or not for bearing nutrition or health claims . one core aim of the regulation is to avoid a situation where nutrition or health claims mask the overall nutritional status of a food product , which could mislead consumers when trying to make healthy choices in the context of a balanced diet ' . report of a who ( world health organization)/iaso ( international association for the study of obesity ) joint technical meeting recently highlighted the importance of using validated nutrient profiling systems and listed a number of possible validation methods . these include assessment of construct validity , that is , testing whether healthy foods ( identified as eligible by nutrient profile system ) make healthy diets , and unhealthy foods ( that is , non - eligible ) make unhealthy diets . the aim of the present study was to assess the construct validity of five nutrient profiling systems , using diet modeling with linear programming for designing healthy and unhealthy diets . the dietary data and the food database were derived from the inca french dietary survey . each food of the food database ( n=597 ) was allocated to one of two classes , eligible and non - eligible , according to each of the five european nutrient profile systems tested . two systems are currently used for food labeling , namely choices v2.2 and green keyhole , two have been proposed to assess food products ' eligibility to claim but that are not currently in use , namely the french afssa system ( agence franaise de scurit sanitaire des aliments ) and the ec system ( european commission draft ) , and foodprofiler , a system in use for self - limiting advertisement to children . using a previously described diet modeling approach , the feasibility of designing healthy or unhealthy diets with eligible foods only , or with non - eligible foods only , was tested for each nutrient profiling system . healthy diets were defined by the fulfillment of a set of a forty nutrient constraints , and unhealthy diets by the nonfulfillment of the same set of nutrient constraints . to ensure realism to the modeled diets , constraints on foods and food groups were included and the possibility to design a 2000-kcal diet was tested . four feasibility tests were used to assess the construct validity of each system . tests a , eating healthily with eligible foods only , and d , eating unhealthily with non - eligible foods only , were used to assess whether the systems respected the nutritional common sense . tests b , eating unhealthily with eligible foods only , and c , eating healthily with non - eligible foods only , assessed more finely the level of permissiveness . the following terminology is used : strict unfeasibility ' means that no mathematical solution can be found at all . when solutions can be found , the range between the minimum and the maximum energy achievable is called the energy range ' . a system is considered as valid when tests a and d are feasible , and tests b and c are unfeasible . the percentage of eligible foods varied between systems : choices : 31.8% green keyhole : 35.6% afssa : 35.8% ec system : 46.5% and foodprofiler : 49.5% . figure 1 shows that all tested systems allowed 2000 kcal healthy diets with eligible foods ( test a ) , and 2000 kcal unhealthy diets with non - eligible foods ( test d ) . regarding test b , all tested systems exclude 2000 kcal from their energy range and were , therefore , considered as unfeasible : strict unfeasibility was observed for choices and green keyhole systems . unfeasibility was observed also for the foodprofiler and ec systems , the maximum energy achievable being 1772 kcal and 1801 kcal , respectively , and for the afssa system , with a narrow and unrealistic energy range ( 587907 kcal ) . regarding test c , test c was feasible for choices and green keyhole ( 2000 kcal healthy diets allowed with non - eligible foods ) and it was unfeasible for afssa and ec systems ( the energy range for test c excluded 2000 kcal but the minimum energy achievable was close to 2000 kcal : 2018 kcal and 2162 kcal , respectively ) . one important result is that , with all tested systems , it was possible to design healthy diets with eligible products and unhealthy diets with non - eligible products ( tests a&d ) , demonstrating that all systems satisfied the nutritional common sense . in line with the latter results , choices was previously presented as valid based on its beneficial impact on dietary quality in modeling studies simulating the replacement of foods not complying with the choices criteria by existing choices - compliant products . nevertheless , choices and green keyhole allowed to design 2000 kcal healthy diets with non - eligible products , and were , therefore , identified as invalid according to this construct validity assessment . in contrast , foodprofiler , afssa and ec systems were identified as valid because they answered as expected to the four tests . the three valid systems showed differences in their level of permissiveness . with the afssa system , it was almost feasible to design a 2000-kcal healthy diet with non - eligible foods ( test c ) , which suggests that some healthy foods are misclassified as non - eligible . therefore , this system rather display a keep the best ' approach when classifying the unhealthy food products . in the opposite , with the foodprofiler and the ec system , it was almost feasible to design a 2000-kcal unhealthy diet with eligible foods ( test b ) , which shows that these systems rather display a stop the worst ' approach by misclassifying some unhealthy foods as eligible . analyzing the foods selected by linear programming in these tests could help identify the misclassified foods , and then fine - tune the systems . the validation method used in the present study is perfectible , for instance by improving the realism of diets using more sophisticated diet modeling techniques . nevertheless , this study revealed that some nutrient profiling systems , among those currently used , show weaknesses by failing this construct validity assessment . among the three systems identified as valid in the present study , the ec system is the less demanding in terms of nutritional information , it would , therefore , be the easiest to implement for regulating nutrition and health claims in europe .

nutrient profiling classifies individual food products according to their nutrient content . according to the who ( world health organization ) , validation is a key step in the development of a nutrient profiling system . the aim was to assess the construct validity of five european nutrient profiling systems ( choices , keyhole , ( afssa ) , european commission ( ec ) system and foodprofiler ) . construct validity was assessed for each of the five - selected nutrient profiling systems by testing whether healthy foods ( that is , identified as eligible by the system ) make healthy diets , and unhealthy foods ( that is , non - eligible ) make unhealthy diets , using diet modeling . the afssa , ec and foodprofiler systems were identified as valid , but differences in their levels of permissiveness suggested some misclassified food products . the two other systems failed the construct validity assessment . among these three systems , the ec system is the less demanding in terms of nutritional information , it would , therefore , be the easiest to implement for regulating nutrition and health claims in europe .

the chronic inflammatory diseases course in the elderly have some specificity regarding their clinical presentation , the presence of comorbidities , and severe illness suggestive of malignancy . the spondyloarthritis ( spa ) involve several disorders sharing common clinical and radiological characteristics with ankylosing spondylitis ( as ) . structural changes usually evolve over years , primarily in the axial skeleton and especially in the sacroiliac joints [ 13 ] . ankylosing spondylitis and spondyloarthritis , in their classical onset , are generally observed in young patients ; clinical onset after the age of 50 years is uncommon . previous studies have considered that patients > 50 years of age had late - onset disease . however , most epidemiological studies evaluating the safety profile of a treatment define elderly patients as those aged > 65 years . all the spondyloarthritis subgroups are represented in the elderly : ankylosing spondylitis , reactive arthritis , psoriatic arthritis , articular manifestations of inflammatory bowel diseases , and undifferentiated spondyloarthritis [ 68 ] . thus , late - onset spondyloarthritis is underdiagnosed in favour of other inflammatory disorders that are more frequently observed in the elderly because the clinical or radiological presentations of late - onset spondyloarthritis are modified in the elderly . they deserve further attention because age population is increasing and new criteria for axial spa including sacroiliitis detected by mri may help the clinician with diagnosis . the aim of this paper is to update the clinical and radiological features of late - onset spondyloarthritis . previous epidemiological series determined a prevalence for late - onset ankylosing spondylitis between 3% and 8% . this prevalence need to be re evaluated because there is new diagnostic criteria for axial spa recently developed by the assessment of spondyloarthritis international society ( asas ) . those criteria will facilitate the diagnosis in young patients with inflammatory back pain and also elderly patients . as or axial spa can be diagnosed from ( i ) the presence of sacroiliitis , evident on mri or radiography , plus at least one spa feature , or ( ii ) the presence of hla - b27 plus at least two spa features . sacroiliitis on imaging was defined as either active ( acute ) inflammation on mri highly suggestive of sacroiliitis associated with spa or definite radiographic sacroiliitis according to modified new york criteria . spa features included inflammatory back pain , arthritis , enthesitis ( heel ) , uveitis , dactylitis , psoriasis , crohn 's disease / ulcerative colitis , good response to nsaids , family history of spa , hla - b27 , and elevate c - reactive protein ( crp ) ( table 1 ) . the clinical spectrum of late - onset spondyloarthritis seems to be as wide as it is in young adults . the patients meet the amor criteria or the european spondyloarthritis study group criteria [ 11 , 12 ] and they have a predominantly axial disease , with spinal symptoms and sometimes peripheral arthritis . the authors described 10 cases of b27-positive men who developed an oligoarthritis together with a large inflammatory pitting edema of the lower extremities , after the age of 50 . all ten patients were male and had moderate involvement of the axial skeleton , oligoarthritis of the lower limbs with pitting oedema in most cases , severe illness with constitutional symptoms , and marked elevation of laboratory parameters of inflammation . responses to nonspecific nonsteroidal anti - inflammatory drugs were poor and symptoms persisted from 1 to several years . five patients developed sacroiliitis during followup and four of them met criteria for ankylosing spondylitis . the clinical presentations described in this report were considered to belong to the group of spondyloarthritis . compared the clinical presentation of late - onset uspa with patients with early onset spa . eight patients with late - onset spa were identified after a retrospective chart review of inpatients and outpatients seen over an 8-year period . late - onset patients had more cervical and dorsal pain , anterior chest wall involvement , peripheral arthritis , aseptic osteitis , and systemic symptoms than patients with early - onset spa . reviewed the files of male patients admitted in their department over a period of 12 years for rheumatoid factor - negative arthritis beginning after the age of 50 . patients with polymyalgia rheumatica , psoriatic arthritis , or crystal - induced arthritis were excluded . of the 105 patients , 29 meet american college of rheumatology criteria for rheumatoid arthritis , 29 met the new york criteria for ankylosing spondylitis , three had reactive arthritis , and 44 had unclassified arthritis . most of these latter patients had oligoarthritis together with inflammatory pitting edema , marked constitutional symptoms , and elevated erythrocyte sedimentation rates . the clinical spectrum of patients with late - onset uspa was studied by olivieri et al . twenty - three patients ( 11 men and 12 women ; 17 were b27 positive and six were negative ) were seen during a 5-year period and followed prospectively . of these , 12 had three or more manifestations of spa including peripheral arthritis , peripheral enthesitis , dactylitis , inflammatory spinal pain , buttock pain , chest wall pain , heart involvement , acute anterior uveitis , and sacroiliitis . only 10 of the 23 patients had peripheral arthritis , three of whom had ankle or tarsus involvement together with the large inflammatory pitting edema described by dubost and sauvezie . of the two patients with only one manifestation , two had peripheral enthesitis , and two had acute anterior uveitis . of the 23 patients , only 15 met the essg or the amor criteria for spa . the clinical spectrum is found as wide as in children and middle age adults and includes patients with pitting edema . the same authors described seven cases of uspa in patients presenting polymyalgia rheumatica ( pmr ) features . all patients with late - onset uspa meeting criteria for pmr at the onset of their disease were seen . all patients had manifestations of spa at the beginning of the disease and two developed these in the following 6 months . the conclusion was that late - onset uspa may have pmr - like features at the beginning of the disease and that the diagnosis is not difficult if the entire clinical spectrum of spa is considered . four reactive arthritis patients among 105 inflammatory arthritis patients > 50 years of age were reported by dubost et al . . in the elderly , psoriatic arthritis is considered to be more severe and to have a less favorable outcome than young - onset psoriatic arthritis , suggesting that there is more frequent use of aggressive or innovative treatments such as anti - tnf in older patients . have prospectively evaluated the presenting manifestations and the 2-year outcome of 60 consecutive patients with psoriatic arthritis , 16 of whom had elderly onset and 50 of whom had younger onset . the elderly group had a significantly higher number of active joints , foot erosions , and levels of serum c - reactive protein and synovial interleukin-1 and interleukin-6 than younger patients . after 2 years the progression rate of the joint damage and the c - reactive protein level were higher in elderly patients than in younger ones . in cantini et inflammatory pitting edema on the dorsum of hands or feet was found in 39 of 183 patients ( 21% ) with psoriatic arthritis and in 18 of 366 controls ( 4.9% ) . standard radiographs to look for sacroiliitis or syndesmophytes contribute little to the diagnosis of late - onset spa , as changes induced by age ( osteoporosis , osteoarthritis , and discarthrosis make it difficult to interpret x - rays . mri is a very helpful imaging method for the early diagnosis of as , that is , at a pre- or nonradiographic stage . mri is a useful diagnostic tool because it has good specificity ( 88% to 98.5% ) . however , mri may have limited sensitivity for detecting low - grade inflammation ( 32%50% ) [ 2530 ] . there has been no specific study of mri assessment of the sacroiliac joints or the spine in patients with late - onset spa , but it is probable that the mri findings will certainly be the same as in the young population . indeed , similar mri changes were seen in 20% of healthy individuals without inflammatory disease , and also in patients with discarthrosis or malignant bone disease ( metastasis ) . combining mri of the sacroiliac joints and spine provides more information than mri of either site alone . no studies have evaluated the diagnostic performance of mri for diagnosing spa in patients who are hla b27-negative and who fail to meet criteria for inflammatory low back pain . most of the studies in which mri contributed to the diagnosis of recent - onset spa were conducted in hla b27-positive patients who had chronic inflammatory low back pain [ 27 , 32 ] . in patients with lops , ultrasound assessment of joint structures may be useful for evaluating synovial and tenosynovial modifications . ultrasonography is a simple and inexpensive investigation that is more sensitive than the physical examination for diagnosing enthesitis related to spa . two recent studies have provided data on the performance of color doppler ultrasonography for assisting in the diagnosis of spa by evaluating inflammation of the sacroiliac joints and spine [ 33 , 34 ] . no study has been done to evaluate the accuracy of this technique in that range of patients . the diagnosis of late - onset axial spa may be easier than lops but care must be taken not to mistake spinal findings . in fact , the recognition of sacroiliitis by standard radiographs is more problematic because of changes induced by age ( osteoporosis , osteoarthritis , and discarthrosis ) . dish and spa have in common the involvement of axial skeleton and extraspinal entheses but their radiological features are different [ 35 , 36 ] . in contrast , a lops may be more difficult to diagnosis with other inflammatory diseases in which remitting distal extremity swelling with pitting edema has been observed include chondrocalcinosis , amyloid arthropathy , systemic lupus erythematosus , mixed connective disease , sjgren syndrome , systemic sclerosis , dermatomyositis , and polyarteritis nodosa [ 3844 ] . rs3pe ( remitting seronegative symmetrical synovitis with pitting edema ) syndrome [ 45 , 46 ] is characterized by an acute onset of bilateral symmetric synovitis involving predominantly the wrist , the carpus , the small hand joints , and the flexor digitorum sheaths associated with a marked dorsal swelling of the hands with pitting edema ( boxing glove hand ) . the disease is sensitive to small doses of steroids and remains in remission after such therapy . since late - onset ankylosing spondylitis or spondyloarthropathy may give rise to polymyalgia rheumatica - like manifestations , this differential diagnosis should be considered . the first point in the differential diagnosis between late - onset uspa and pmr is the presence of inflammatory swelling with pitting edema due to tenosynovitis of the extensor tendons of hand or foot in both conditions . the second point is the possibility that late - onset uspa may begin with pain and stillness in the shoulders and hip girdles mimicking pmr . in clinical trials evaluating the efficacy of anti - tnf agents in as , patients > 65 years of age were generally excluded . thus , data on the efficacy and safety of anti - tnf agents in late - onset spa are lacking . indirect experience of the use of tnf blockers in the elderly derives from studies in ra , although ra and as patients are not comparable . based on the available literature , some recommendations for the use of anti - tnf agents in elderly ra patients have been proposed [ 49 , 50 ] . these recommendations , which are also applicable to patients with late - onset spa , are careful selection of the patient before initiating the tnf-blocking agent , evaluation of comorbidities , and estimation of the risk for severe and opportunistic infections . the spondyloarthritis are most typically seen in younger patients . however , late - onset spa after the age of 50 years is uncommon . the clinical spectrum of late - onset as and spa seems to be as wide as it is in young adults . two main clinical presentations . the patients may have a predominantly axial disease , with spinal symptoms and sometimes peripheral arthritis . the patient may present with late - onset peripheral spondyloarthritis ( lops ) with distal inflammatory swelling with pitting edema on the dorsum of feet or hands together with peripheral arthritis and peripheral enthesitis . the patients may have a predominantly axial disease , with spinal symptoms and sometimes peripheral arthritis . the patient may present with late - onset peripheral spondyloarthritis ( lops ) with distal inflammatory swelling with pitting edema on the dorsum of feet or hands together with peripheral arthritis and peripheral enthesitis . some patients show only one manifestation of the b27-associated disease process for years and need to be evaluated by the new diagnostic criteria for axial spa ( table 1 ) . if the clinical features do not immediately establish the diagnosis , an anterior posterior radiograph of the pelvis is useful to look for sacroiliitis . when this investigation fails to show sacroiliitis , the authors recommend mri of the sacroiliac joints and thoracolumbar spine to look for inflammation , in keeping with recent recommendations ( table 2 ) . specific studies evaluating the benefit / risk ratio of tnf-blocking agents in late - onset spa patients are required .

the last few years have witnessed considerable progress in the diagnosis and treatment of spondyloarthritis ( spa ) . tools are now available for establishing the diagnosis at an early stage , when appropriate treatment may be able to control the inflammatory process , limit the functional impairments , and improve quality of life . late - onset spa after the age of 50 years is uncommon . all the spondyloarthritis subgroups are represented in the elderly . thus , late onset spondyloarthritis is underdiagnosed in favour of other inflammatory disorders that are more frequently observed in the elderly because the clinical or radiological presentations of late - onset spondyloarthritis are modified in the elderly . they deserve further attention because age population is increasing and new criteria for axial spa including sacroiliitis detected by mri may help the clinician with diagnosis . specific studies evaluating the benefit / risk ratio of tnf-blocking agents in late onset spa patients are required .

microhardness is the gold standard parameter to observe alterations of mechanical properties in mineralized tissues and a good predictor of the other important mechanical properties such as young 's modulus and yield stress . nanoindentation technique , which is the latest technology in hardness measurement , has been developed to investigate surfaces at smaller scales , especially for thin surface coatings and films . even though nanoindentation studies have been published widely in the last decade , only the thin superficial layer of tissues can be examined . while knoop indenter is able to reveal deformations 20 m in length , as small as 5 m area in diameter can be measured by vickers indenter ; in other words , vickers indenter is more sensitive to plastic deformations . extracted human teeth have a crucial importance as a fundamental material in in vitro dental studies . following extraction , their maintenance immediately requires 100% humidity , and the easiest storage is immersing the teeth into aqueous solutions , such as de - ionized water , thymol , and hanks balanced salt solution ( hbss ) . nonetheless , storage conditions of extracted teeth can alter the mechanical properties of dental tissues , which can greatly affect the result of the mechanical tests during experimental processes . it is known that mechanical properties of dentin and enamel are dependent to their mineral content , and aqueous solutions can result in mineral leaching while preserving the hydration of dental hard tissues . in this study , the null hypothesis was tested that the microhardness of nonsterile intact teeth does not significantly change if teeth are kept for 12 months in a jar filled with de - ionized water , 0.2% glutaraldehyde , hbss , 0.1% sodium hypochlorite ( naocl ) or 0.1% thymol at room temperature . caries free , permanent premolars were extracted for periodontological purposes after the approval of the ethics committee . after calculus and soft tissue removal by curettes , 12 nonsterile teeth were immediately put into one of the following storage solutions : de - ionized water ( ph ~6.5 ) , 0.2% glutaraldehyde ( ph ~4.8 ) , hbss ( hbss , with phenol red , with calcium and magnesium , ph ~7.5 , sigma - aldrich corporation , st . louis , mo , usa ) , 0.1% naocl ( ph ~10 ) , and 0.1% thymol ( ph ~9.1 ) . solutions were not replenished during the 12 months storage , which limits the dissolution of the inorganic fraction of teeth . six teeth from each group were taken out of the storage solution at the 2 month of the storage , and the other six teeth were taken out at the 12 month . teeth with the vestibular surfaces facing up were horizontally embedded in polyester resin . to prepare a flat surface which exposes enamel and dentin together , teeth crowns were ground 2 mm on their vestibular surface using 180 , 220 , 320 , 500 , 800 , 1000 , 1200 grit silicon carbide papers under copious water - cooling , followed by polishing with 0.05 m alumina slurry using a low - speed metallurgical polisher . after transferring teeth to the vickers hardness testing machine ( buehler , lake bluff , il , usa ) six indentations on enamel and six indentations on dentin were done by a pyramid diamond indenter tip with 100 g load for 15 s. on enamel and dentin , the indentations were started 200 m away from dentino - enamel junction and made toward the coronal surface on enamel and towards apical end on dentin , with keeping approximately 200 m distance between the indentations . means of the hardness values ( hv ) for enamel and dentin were separately calculated per sample , and data was processed using spss 15.0 ( spss , inc . , chicago , il , usa ) . first , normalization of the data was evaluated , and statistically homogenous data distribution was verified using one - sample kolmogorov - smirnov test , and two - way anova was used . vickers hardness value was calculated using the formula : hv = 1.854 fd . applied load is f ( kgf ) , and right after the indentation , a diagonal length of the pyramid - shaped impression on the substrate is d ( mm ) . the hardness of the teeth stored in different solutions was compared , no statistical differences were found depending either on the solution used or the periods of storage ( p > 0.05 ) [ figure 1 ] . mean hv of enamel and dentin microhardness of enamel and dentin at the 2 and the 12 month . w : deionized water , g : glutaraldehyde - 0.2% , h : hanks balanced salt solution , n : naocl - 0.1% , t : thymol - 0.1% for each solution type , microhardness at the 12 month was significantly less than that at the 2 month storage ( two - way anova , p = 0.001 ) ; however , the decrease rate in microhardness was similar in all groups [ table 2 ] . in this study , the null hypothesis was rejected since the microhardness of nonsterile intact teeth significantly changes if teeth are kept for 12 months in de - ionized water , 0.2% glutaraldehyde , hbss , 0.1% naocl or 0.1% thymol at room temperature . results showed all storage solutions decrease the hardness of the teeth in a similar fashion . however , results also showed that storing nonsterile intact teeth for 2 months in these solutions with mentioned concentrations maintain the microhardness of teeth . after extraction , solution where nonsterile teeth are collected is not changed due to hygienic concerns in a clinic dedicated to patient - care . hence , teeth sometimes are kept in the storage solutions for months until a sufficient number of teeth are collected for an experiment . it is known that sterilization of teeth can only be achieved by the gamma irradiation ; other methods such as ethylene oxide , dry heat , and autoclave cause significant changes in physical and chemical composition of dental tissues . thus , storing extracted teeth in an antimicrobial solution is the most preferred method where access to gamma irradiation is limited . antimicrobial agents in which extracted teeth are stored can penetrate into dental tissues and may cause undesired effects during experimental studies . to avoid that , a jar filled with de - ionized water is generally preferred during the collection of teeth . regarding replenishment of the storage solutions , baillif et al . showed that increase in inorganic material leaching with more frequent replenishment of saline solution . in the present study , storage solutions were not replenished for 12 months to minimize the dissolution of the inorganic fraction of teeth . irrelevant to the solution used , average vickers micro hv obtained after 2 months of storage ( changing in between 315357 for enamel and 6467 for dentin ) were in agreement with the previous studies results . in a study , even after a single day of storage in de - ionized water , a 25% decrease in the hardness of both enamel and dentin was demonstrated ; however , exposed tooth tissues were introduced to storage solutions in mentioned study . in present study , even though the teeth stored in solutions were intact , a microhardness decrease of 4763% in enamel and 3553% in dentin was found between the 2 and 12 months of storage [ table 2 ] . no long - term study was found in the literature showing hardness change of the teeth by storage solutions . thus , a most relevant , but a short - term study done by habelitz et al . was referred . they observed a 77% decrease in hardness of enamel and a 63% decrease for dentin after storing sterile teeth slices in de - ionized water for 2 weeks . however , their results were based on nanoindentation measurements . hence , to compare their hardness results with the results of the present study , their hardness unit ( gpa ) was converted to vickers hv . to convert gpa to hv , gpa hardness value is divided by 0.009807 . according to the results of this calculation , it is concluded that habelitz et al . detected very low hv after storage ; approximately 82 hv for enamel and 40 hv for dentin . however , in this study , hardness of enamel was 177 hv at the end of the 1-year storage in de - ionized water [ table 1 ] , in spite of the fact that nanoindentation hardness is about 1030% greater than the microhardness . as quickly as 2 weeks , can be explained by the submerging of the exposed tissue slices into the storage solutions . it is known that hardness of the outer enamel layer is much greater than the layers underneath , and this layer can limit the penetration of the storage solutions when compared to the exposed dentin . therefore , solutions can show their dissolution effect earlier on enamel and dentin if submerged samples were sectioned . in addition , microhardness test results obtained from tooth slices can be misleading due to different thickness of tissues on each slice . outer tissues of teeth crown were evaluated 200 m intervals with using six indentations in the present study , and ~1.2 mm superficial layer of dentin was scanned . however , enamel was thoroughly examined because it can only be as thick as 1.5 mm at the cusp of premolar teeth . thymol solutions at 0.1% concentration have been widely used to store teeth prior to mechanical testing . the same concentration of thymol and naocl solutions was compared in this study , and no significant difference was found in their effect on microhardness of teeth . naocl solutions at an efficient concentration ( 2.5% ) for root canal irrigation significantly decrease dentin hardness in a very short duration such as 15 min . however , a low concentration of naocl solution such as 0.1% was not more effective than de - ionized water in the weakening of hard tissues . wemes and arends reported that 2% glutaraldehyde resulted in a remarkable decrease ( 15% ) in the hardness of bovine dentin after 20 min ; however , a reverse effect occurred after a relatively long period of storage : 15% hardening was observed compared to sound dentin after 2 days of storage . ten times diluted concentration of glutaraldehyde ( 0.2% ) was used in this study , and even though there were no statistical differences between the groups , microhardness of teeth stored in glutaraldehyde ( 0.2% ) were larger than that of other groups at 2 month . as mentioned in the conclusion of the study of wemes and arends , hardening of dentin the mechanism preventing the dissolution of the minerals in dental hard tissues can be explained by the limited transport of the ions such as calcium and phosphate out of the cross - linked organic material . in a previous study , it was shown that 2% glutardialdehyde can be able to penetrate 2-mm dentin slabs approximately 200 m in a week . caries - free , intact teeth were used in the present study ; so , penetration of the glutaraldehyde solution most likely would occur via the apical foramen , or cementoenamel junction where dentin tissue may directly contact and absorb the solution . even though the penetration rate in enamel is not known , glutaraldehyde solution may completely penetrate intact teeth in 12 months . at the end of 1-year of storage , since the inorganic fraction of enamel ( ~85% ) is greater than that of dentin ( ~50% ) , a larger decrease in hardness was observed in enamel . briefly , storing teeth for 12 months in glutaraldehyde ( 0.2% ) resulted in a dramatic decrease in hardness compared to other storage solutions [ table 2 ] in the present study . this observation may be explained by the early demineralization of the tissues by the acidic environment ( ph ~4.8 for 0.2% glutaraldehyde ) followed by long - term aqueous degradation of enamel and dentin , since glutaraldehyde concentration may not be high enough to contribute cross - linkages in the collagen fibrils . balanced salt solution with highly concentrated ca , mg , na , po4 , and cl ions that do not dissolve calcium phosphate composition of teeth and did not change the hardness of teeth in 2 weeks . it was previously shown that hbss with highly concentrated ca , mg , na , po4 , and cl ions does not dissolve calcium phosphate composition of teeth and does not change the hardness of teeth in 2 weeks . in this study , a similar hbss solution with ions was used ; however , hardness of teeth was no different than the teeth in other storage solutions including 0.1% naocl and de - ionized water . this result can be attributed to the storage periods in hbss , of which constant ion concentration may not be able to compensate the leaching of teeth beyond 2 weeks in the present study . the hardness of teeth stored for 2 months in de - ionized water , 0.2% glutaraldehyde , hbss , 0.1% naocl or in 0.1% thymol was acceptable for in vitro tests . however , neither diluted antimicrobial solutions nor hbss prevented a decrease in microhardness of nonsterile teeth after 12 months storage . hence , to test the applicability of a storage solution , long - term studies evaluating changes in mechanical properties of teeth are necessary .

objective : the aim of this study was to determine alterations in microhardness of crown dentin and enamel , after 2 and 12-month storage in de - ionized water , 0.2% glutaraldehyde , hanks balanced salt solution ( hbss ) , 0.1% sodium hypochlorite ( naocl ) or 0.1% thymol.materials and methods : freshly extracted , nonsterile 60 intact human premolars were distributed to five groups . six teeth from each group were evaluated after two , and other six teeth were evaluated after 12 months storage . after grinding and polishing of teeth , vickers hardness was evaluated with making indentations on enamel and dentin , using a pyramid diamond indenter tip exerting 100 g load for 15 s.results:after 2 months storage in solutions , range of the hardness values ( hv ) of enamel and dentin were in between 315357 and 6467 , respectively . however , 12 months storage of the teeth resulted in a statistically significant decrease in microhardness when compared to microhardness of teeth stored for 2 months ( p = 0.001 ) . although the differences were not significant regarding solutions , all solutions decreased the microhardness both in enamel and dentin ( p > 0.05 ) . however , decrease in microhardness was relatively less in de - ionized water and thymol solutions while glutaraldehyde decreased microhardness the most : 63% for enamel and 53% for dentin.conclusions:microhardness of enamel and dentin was in an acceptable range when teeth were stored for 2 months in de - ionized water , glutaraldehyde , hbss , naocl or in thymol ; thus , teeth kept up to 2 months in these solutions can be used for mechanical in vitro tests . however , 12 months storage significantly decreased the microhardness of enamel and dentin .

this video is also available to watch on http://videos.springer.com/. please search for the video by the article title . the objective of this study was to identify new tactile imaging and muscle contraction markers to characterize female pelvic floor conditions . vaginal tactile imaging [ 1 , 2 ] allows 3-d quantitative elasticity assessment of pelvic floor support structures and carries a potential in assessment of surgical repair . we designed a new vaginal tactile imaging probe that images the entire vagina , the pelvic floor support structures , and pelvic floor muscle contractions . the probe has an orientation sensor , temperature sensors , and 96 pressure sensors positioned every 2.5 mm along both sides of the probe . the examination procedure includes four steps.step 1.probe insertion : this step provides the pressure responses ( p ) for vaginal anterior and posterior compartments along the entire vaginal length . we can use this information to calculate pressure gradients ( grp ) and anatomical dimensions.step 2.probe elevation : this step provides the pressure responses for the apical anterior and posterior compartments that are related to pelvic floor support structures.step 3.probe rotation : this step provides the pressure patterns for the left and right sides of the vagina ( circumferential tactile image from vaginal walls).step 4.pelvic floor muscle contractions : this step provides the muscle dynamic pressure responses ( dp ) of the pelvic floor muscle contraction recorded from opposite sides along the entire vaginal length . probe insertion : this step provides the pressure responses ( p ) for vaginal anterior and posterior compartments along the entire vaginal length . we can use this information to calculate pressure gradients ( grp ) and anatomical dimensions . probe elevation : this step provides the pressure responses for the apical anterior and posterior compartments that are related to pelvic floor support structures . probe rotation : this step provides the pressure patterns for the left and right sides of the vagina ( circumferential tactile image from vaginal walls ) . pelvic floor muscle contractions : this step provides the muscle dynamic pressure responses ( dp ) of the pelvic floor muscle contraction recorded from opposite sides along the entire vaginal length . in 2013 two patients were excluded from the data analysis because they had previously had pelvic floor surgery . the analyzed data set included 20 subjects aged from 41 to 70 years . among them four had normal pelvic floor conditions , four stage i , seven stage ii , four stage iii , and one stage iv prolapse . a standard physical examination was performed , including a bimanual pelvic examination , pelvic organ prolapse quantification ( pop - q ) , assessment of tissue rigidity , and assessment of pelvic floor muscle tone . the tactile imaging data from all examinations were reviewed in a blinded fashion with no knowledge of the subject s pelvic floor conditions to avoid bias in the data review process . the clinical information was then added to this data set after the tactile imaging data ( pressure , pressure gradients , muscle contracting response ) were finalized . one - way analysis of variance ( anova ) ( pa ) , paired t test ( pt ) , and pearson s correlation coefficients ( r ) were calculated to determine whether the various parameters showed dependence on the pelvic floor conditions . the subjects were asked to complete an assessment of comfort and pain levels for the tactile imaging procedure . we identified the following parameters as potential markers to characterize the female pelvic floor conditions . site 1 corresponds to the lower one third of the vagina and site 2 to the upper one third of the vagina . we found that nine parameters are sensitive to prolapse conditions ( p < 0.05 for one - way anova and/or p < 0.05 for t test with correlation factor r from 0.73 to 0.56 ) . these parameters demonstrate a mild - moderate correlation with women age and parity ( see table 1 ) . during step 4 part of the identified markers also demonstrates correlation with patient age and parity . a typical examination consisting of four steps takes 12 min . of the patients , 54 % classified vti comfort level as more comfortable than manual palpation , 36 % as the same , and 10 % as less comfortable than manual palpation . of the patients , 73 % classified vti pain as none , 24 % as mildly painful , and 3 % as a painful.table 1summary for 11 parameters identified as potential markers for pelvic floor characterizationno.marker locationmeasured / calculated valueinterpretationexamination step ( no.)one - way anova , p vs prolapse staging t test , p vs prolapse stagingcorrelation coefficient , r vs prolapse stagingcorrelation coefficient , r vs agecorrelation coefficient , r vs parity1anterior site 1pressuretactile feedbackprobe insertion ( 1)0.0110.0060.730.170.222anterior site 1pressure gradienttissue elasticityprobe insertion ( 1)0.0890.0200.610.130.233posterior site 1pressuretactile feedbackprobe insertion ( 1)0.0080.0120.710.710.390.374posterior site 1pressure gradienttissue elasticityprobe insertion ( 1)0.0140.0200.690.400.315posterior site 1pressuretactile feedbackprobe elevation ( 2)0.0300.0130.630.520.266posterior site 2pressuretactile feedbackprobe rotation ( 3)0.350.0610.400.260.137sides site 1pressuremuscle strengthprobe rotation ( 3)0.0910.0480.660.260.118anterior site 1pressure changemuscle strengthmuscle contraction ( 4)0.1020.0570.580.240.009anterior site 2pressure changemuscle strengthmuscle contraction ( 4)0.0670.0160.560.110.3310posterior site 1pressure changemuscle strengthmuscle contraction ( 4)0.0800.0190.610.150.2111posterior site 2pressure changemuscle strengthmuscle contraction ( 4)0.0460.580.390.200.27 summary for 11 parameters identified as potential markers for pelvic floor characterization our findings suggest that the tactile imaging markers such as pressure , pressure gradient , and dynamic pressure response during muscle contraction may be used for further quantitative characterization of female pelvic floor conditions . h. van raalte : grant / research support ; shareholder of advanced tactile imaging , inc . v egorov : grant / research support ; ceo and shareholder of advanced tactile imaging , inc .

introduction and hypothesistactile imaging ( ti ) is the high - definition pressure mapping technology which allows recording pressure patterns from vaginal walls under applied load and during pelvic floor muscle contraction . the objective of this study was to identify new tactile imaging and muscle contraction markers to characterize female pelvic floor conditions.methodsthe study subjects included 22 women with normal and prolapse conditions . they were examined by a new vaginal tactile imaging probe that images the entire vagina , the pelvic floor support structures , and pelvic floor muscle contractions.resultswe identified 11 parameters as potential markers to characterize the female pelvic floor conditions . these parameters correlate with prolapse conditions , patient age , and parity.conclusionsour findings suggest that the tactile imaging markers such as pressure , pressure gradient , and dynamic pressure response during muscle contraction may be used for further quantitative characterization of female pelvic floor conditions.electronic supplementary materialthe online version of this article ( doi:10.1007/s00192 - 014 - 2549 - 9 ) contains supplementary material , which is available to authorized users . this video is also available to watch on http://videos.springer.com/. please search for the video by the article title .

visual impairment in infancy results in a variety of developmental disorders in children.1 the etiology , degree of impairment , age of onset of the vision loss and other factors define the severity of the defects in the general development of the child.2 according to the 10 revision of the international statistical classification of diseases and problems related to health , a person has low vision when their vision in the best corrected eye is within the 6/18 and 3/60 ( categories 1 and 2 of visual loss ) , and they are blind when this value is below 3/60 ( categories 3 , 4 , and 5).3 the prevalence and causes of visual impairment in children ( those below 16 years old , according to unicef ) are variable across different regions of the world , and these statistics are related to social , economic and cultural factors.4,5 foster estimate the number of blind children in the world to be around 1,500,000 , with 75% of this population in asia and africa . in developed countries , genetic causes and congenital or prenatal birth problems are more prevalent , while nutritional factors , ocular infections , cataracts and congenital glaucoma are more often associated with the condition in developing countries.410 congenital glaucoma occurs in one out of 10,000 live births.2 visual loss secondary to congenital glaucoma may occur as a consequence of optical nerve damage , corneal opacities , cataracts and amblyopia . even though the success rate of early treatment is approximately 70 to 80% , only 35% of all patients will have visual acuity better than 20/50 , and 2% to 15% will remain blind.2 , 11 children who suffer from visual impairment as a result of congenital glaucoma should be referred to a low vision clinic , with the aim of improving their future general performance . the objective of ophthalmic low vision therapy in children is to improve visual function through optical and non - optical aids , and/or electronic or computer devices . the aim is to modify ( through magnification , filtration or sometimes minification ) the retinal image , and to improve environmental conditions related to visual function.12 magnification of the retinal image is the main resource in cases of low vision , and most treatment approaches involve one of four basic techniques : increasing the relative size of the object itself , increasing its relative size by reducing its relative distance , angular magnification ( telescopes ) and amplification by electronic projection.13 optical devices provide various levels of magnification depending on their dioptric power , and must be used in accordance with certain criteria . the optimal performance of low vision aids requires an ophthalmologic low vision evaluation , measurement of the visual response , selection of the aid , and training for efficient use of the device and prescription.13 according to faye ( 1990 ) , about 90% of patients with low vision can benefit from the use of optical devices . video magnification and non - optical aids can be used alone or in conjunction with optical devices . the objective of the present study was to evaluate data from a population of 100 children with congenital glaucoma that were assessed at the congenital glaucoma unit and the low vision unit of our facility . our goal was to analyze their visual response with optical correction and use of low vision aids . the authors conducted a retrospective study of one hundred patients with bilateral congenital glaucoma who were assessed , submitted for surgery or clinical treatment at the congenital glaucoma unit at our facility , and who ultimately presented with final intraocular pressure below 20 mm hg . patients with other associated disabilities or with no light perception were not included in this study . the mean age of the studied patients was 6.3 years ; the youngest was 1 month old and the oldest was 16 years old . forty - nine percent were of school age ( 6 16 years old ) . at the low vision unit , all the patients underwent the following exams , all of which were administered by the same ophthalmologists : a complete medical record of the patient was obtained , including a fundamental report regarding their previous treatment and information about their visual difficulties . evaluation of visual function : 2.1 - visual acuity : for children under 3 years of age , teller acuity cards were utilized . for children above 3 years old but not yet literate , lea symbol charts were employed . the feinbloom chart was utilized for very low acuity children , and the ferris - bailey etdrs table was used for literate children . 2.2 - to assess color vision , the ishihara test and the pv-16 ( precision vision color ) test were used . 2.3 - evaluation of contrast sensibility : with collaborative children , two kinds of test were used : the lea symbols low contrast test and the vcts 6500 ( vistech ) . 2.4 - visual field : the confrontation test was used in non - collaborative children , and the goldmann perimeter was used in collaborative children . the amsler test was used for the detection of central scotomas , and also to evaluate the pattern of vision of the studied patients . from this evaluation , children with a stable ocular condition were treated with refraction , prescription of optical corrections for refractive errors and low vision aids . this study evaluates the best corrected visual acuity in the better eye , the prescribed optical correction , and the visual acuity obtained with the recommended optical low vision aid(s ) . the best corrected visual acuity in the better eye was classified in degrees of visual impairment according to the tenth revision of international statistical classification of diseases and related health problems3 and by the international council of ophthalmology.14 the values of the prescribed optical corrections for refractive errors were expressed using spherical equivalents . low vision aids were used for children and adolescents of school age , including hand and stand magnifiers and special glasses for near vision , and telescopes of varying dioptric power and magnification for distance vision . in terms of visual acuity , 2% of the patients presented normal vision ; 29% presented mild vision loss ; 28% presented moderately low vision ; 15% presented severe low vision ; 11% presented profound low vision , and 15% presented near blindness ( table 1 ) . optical correction was recommended for 68 ( 68% ) of the patients , with 57 corrected in both eyes , and 11 corrected in only one eye ( total : 125 eyes with optical correction ) . regarding the optical prescriptions , 80% were corrections for myopia and 20% were for hyperopia and astigmatism . spherical equivalents between 4.00 and 8.00 diopters constituted 22.4% of the optical prescriptions ; 28% were between 4.00 and 0 diopters , and 17.6% were between 8.00 and 12.00 diopters ( table 2 ) . all of the optical aids for distance were telescopic manual systems for one eye only , and the magnifications used were 2.8 ( 32.4% ) , 620 ( 23.5% ) and 4.212 ( 20.6% ) ( table 3 ) . optical aids for near vision were necessary for 6 ( 6% ) of the patients , and the most commonly prescribed were illuminated stand magnifiers of + 38 aspheric diopters ( 33.4% ) , 2x reading bar stand magnifiers ( 33.4% ) , illuminated stand magnifiers of + 28 aspheric diopters ( 16.6% ) , and high plus lenses of + 24 aspheric diopters assembled in spectacles for monocular use ( 16.6% ) ( table 4 ) . of the school - aged children , 69.3% had optical aids prescribed for distance ( telescopes ) and 12.2 % had optical aids prescribed for near vision . the visual acuity values of the 34 children for whom optical aids were prescribed are listed in table 5 the distribution of best corrected visual acuity in the better eye of this group was as follows : near normal vision , 11.8% ; moderate low vision , 58.8% ; severe low vision , 11.8% and profound low vision , 17.6% . with the use of optical aids for distance ( telescopes ) , we observed the following distribution : 32.4% with normal visual acuity values , 41.2% with mild vision loss , 20.6% with moderate low vision and 5.8% with severe low vision . the visual outcome of a child with congenital glaucoma is closely related to the age at which the diagnosis is made and the subsequent treatment trajectory . a familial history of glaucoma should be taken into account as early as possible.15 assessment of visual function in children with congenital glaucoma must be initiated at the time of diagnosis , so that these data may be used as a reference during follow - up . in the present study , 28% of the patients presented with moderate low vision corneal opacities , uncorrected refractive error , anisometropic or strabismic amblyopia and optic nerve lesions can all contribute to poor vision in these children . corneal edema during the first three months of life leads to vision worse than 20/200 in approximately 50% of these children.16,17 corneal edema results from elevated intraocular pressure and is often the presenting sign in infants younger than 3 months . microcystic edema initially involves the corneal epithelium but later extends to the stroma , often accompanied by one or more breaks in descemet membrane ( haab striae ) . intraocular pressure reduction resolves corneal edema but a scar will remain permanently at the haab striae site.11 optical correction was prescribed in 68% of the patients , and in the majority of these individuals the correction was for myopia and/or myopic astigmatism ( 80% ) . the correlation between myopia and glaucoma is due to the increase in the axial diameter of the eye as a consequence of the high intraocular pressure.1620 astigmatisms are usually related to corneal irregularities ( unequal expansion of the anterior segment , corneal scarring and opacification or dislocation of the lens).16,17 amblyopia may occur when refractive errors were not corrected earlier , especially in unilateral cases . according to fonda ( 1986 ) , about 15% of patients that attend a low vision clinic require only optical correction of their refractive errors.17,19 in the present study , 49% of the patients were between 6 and 16 years old ( school age ) , and 69.4% had been prescribed optical devices . telescopic systems ( angular magnification ) , both monocular and manual , were employed to improve visual resolution at a distance , primarily to assist with reading texts on a blackboard . telescopic systems with low magnification such as these are frequently used by children of pre - school and school age due to their ease of manipulation and their large field of vision . they are beneficial in cases of retraction of the visual field , reduction of image illumination , parallax movements and also in mitigating the disturbance of space perception that occurs with all optical devices.21 the daily activities of a person can usually be adequately performed with a corrected visual acuity of around 20/40.21 the use of telescopic systems in visually impaired school children should be promoted , even for school activities , and children that need them should receive them as early as possible . in this way , we can increase their visual ability , avoid losing precious development time and help them understand the benefits of their use . 12,22 patients with visual acuity better than 20/400 will have a greater chance of success with the use of optical aids . 13,23,24 in the present study , we observed that of the 34 children and adolescents who were prescribed optical devices , 28 ( 45% ) presented with visual acuity of better than 20/400 . optical aids for near vision were prescribed less often ( 6% of all patients ) . a larger range of accommodation in the child allows for an enlargement of the retinal image by decreasing the distance between the eye and the object under inspection while keeping it in focus . many children with optical correction for myopia were simply advised to take off their glasses and move closer to the text . this strategy permits an enlargement of the image of the text by decreasing the relative distance , and it increases visual comfort through the use of less accommodation . according to lindsted ( 1986 ) , some children with low visual acuity present with inadequately developed visual accommodation as a consequence of a lack of positive input from the well - focused images that children with normal vision regularly perceive.21 this alone could justify the use of additional plus lenses for near vision . ophthalmologists should collaborate with the family and schoolteachers in order to explain the disease and offer expert advice regarding the use of optical correction along with the prescribed optical and/or non - optical devices . this may help fully integrate children with low vision into school settings and social environments.12,21 the importance of the school staff in observing the visual difficulties of the child and their role in referring those in need to specialized medical services can not be overemphasized . in children with congenital glaucoma , the first priority is clinically controlling the disease . however , it is also necessary to prescribe optical correction for refractive errors and low vision aids as needed , and to schedule a program of future evaluations and careful assessments of their visual function . in conclusion , children with low vision due to congenital glaucoma can clearly benefit by having their refractive errors corrected and by using optical low vision aids . this study suggests that it is important to stimulate the efficient use of vision in infancy , as this promotes the global development of these children , improves their activity profiles , and contributes to the process of school and social integration .

introductioncongenital glaucoma is frequently associated with visual impairment due to optic nerve damage , corneal opacities , cataracts and amblyopia . poor vision in childhood is related to global developmental problems , and referral to vision habilitation / rehabilitation services should be without delay to promote efficient management of the impaired vision.objectiveto analyze data concerning visual response , the use of optical correction and prescribed low vision aids in a population of children with congenital glaucoma.methodthe authors analyzed data from 100 children with congenital glaucoma to assess best corrected visual acuity , prescribed optical correction and low vision aids.resultsfifty-five percent of the sample were male , 43% female . the mean age was 6.3 years . two percent presented normal visual acuity levels , 29% mild visual impairment , 28% moderate visual impairment , 15% severe visual impairment , 11% profound visual impairment , and 15% near blindness . sixty - eight percent received optical correction for refractive errors . optical low vision aids were adopted for distance vision in 34% of the patients and for near vision in 6% . a manual monocular telescopic system with 2.8 magnification was the most frequently prescribed low vision aid for distance , and for near vision a + 38 diopter illuminated stand magnifier was most frequently prescribed.discussion and conclusioncareful low vision assessment and the appropriate prescription of optical corrections and low vision aids are mandatory in children with congenital glaucoma , since this will assist their global development , improving efficiency in daily life activities and promoting social and educational inclusion .

one of the main challenges of the post - genomic era is the understanding of the mechanisms that control the spatio - temporal regulation of gene expression . the fate of newly synthesized mrna with respect to its nucleo - cytoplasmic transport , stability , translation efficiency and subcellular localization is determined at the post - transcriptional level . such regulation is mostly mediated by cis - acting elements located in the 5 and 3 untranslated regions of mrnas ( 5utr and 3utr ) ( 1 ) and mirnas interacting with their specific targets in 3utrs ( 2,3 ) . various specific functional sequence elements and mirna targets have been identified and characterized in mrna utrs . these elements usually correspond to short oligonucleotide tracts whose biological activity relies on a combination of their primary sequence and specific secondary structure . these motifs act either as target sites for rna binding factors or interact directly with the translation machinery . additionally , mirna targets , usually located in the 3utr , present a very degenerate complementarity with the mirnas , tolerating several mismatches , gaps and g u pairings , outside of 68 bp continuous seed region at the 5-end of the mirna . additionally , some utrs may be targeted by complementary natural antisense transcripts masking rna binding protein or mirna binding sites ( 4 ) . notably , it is now clear that the same gene may generate several transcript variants , through the use of alternative sites for the initiation and termination of transcription and through alternative splicing . alternative transcripts can differ both in the coding and in the untranslated regions ( 5 ) . specifically , alternative 5 and 3utrs may differentially modulate the gene expression due to the presence of different combinations of functional motifs and mirna targets . the availability of a large collection of functionally related sequences such as utrs is invaluable for structural and functional analyses and for a better understanding of the specific role of different variants . to address this issue we have developed a new version of utrdb , a collection of 5 and 3 utr sequences derived from eukaryotic mrnas , where the entries have been organized in a gene - centric structure in order to provide relevant information about splicing variants . sequences collated in utrdb were recovered from the national center for biotechnology information ( ncbi ) refseq transcripts ( 6 ) using custom software . for human genes , a more comprehensive collection of utrs is available [ derived from the full set of over 300 000 alternative full - length transcripts collected in aspicdb ( 7 ) ] generated by a thorough analysis of all available est / mrna data . all utrdb entries are further annotated for the occurrence of validated regulatory elements , conserved elements and structured rnas , and mirna targets ( see below ) . furthermore , the completeness of 5utrs is assessed by the occurrence of mapping cage tags ( 22 ) ( if available ) and that of 3utrs by the occurrence of a polya signal and/or a polya tail . we have also further expanded utrsite , a collection of regulatory elements located in 5 and 3 utrs and whose function and structure have been experimentally determined and published . the utrsite collection may prove useful in automatic annotation projects of unknown expressed sequences as well as for finding previously undetected signals in known sequences . in the present release , the information for each utrsite entry has been further enriched including data on functional interacting rna - binding proteins . the gene - centric structure of utrdb facilitates a full integration with all possible gene attributes collected in the ncbi gene database ( 8) or other genomic resources such as the ucsc genome browser ( 9 ) . in this way , the retrieval of specific utr subsets is possible based on the features associated with each gene , for example a go term ( 10 ) , a mim identifier ( 11 ) or a unigene accession ( 12 ) . utrdb entries are automatically generated through the accurate parsing of the feature table of ncbi refseq and aspicdb transcripts for the utref and utrfull sections of utrdb database , respectively . aspicdb contains all possible transcript isoforms for a gene reconstructed by using all available transcript and est sequences as described in ( 13 ) . utr entries are then annotated for the occurrence of tandem and interspersed repetitive elements by using repeatmasker ( v3.2.8 , march 2009 ; a.f.a . smit , r. hubley & p. green repeatmasker at http://repeatmasker.org ) , and known regulatory motifs collected in the utrsite database , as detailed in ( 14 ) . each utrsite entry ( figure 1 ) is prepared / reviewed / updated by expert scientists ( in many cases , those who performed the experimental analysis ) by using a suitably developed submission tool ( 15 ) . the general information section includes the pattern syntax of the regulatory motif in a format suitable for patsearch software ( 23 ) and the number of hits / kb expected in a sequence collection of randomly generated sequences of the same nucleotide composition of utrdb . the cross - link to the rfam database ( 24 ) , transcripts , genes and rna binding proteins , if available are also provided , as well as all relevant references ( not shown here ) . sample utrsite entry . the general information section includes the pattern syntax of the regulatory motif in a format suitable for patsearch software ( 23 ) and the number of hits / kb expected in a sequence collection of randomly generated sequences of the same nucleotide composition of utrdb . the cross - link to the rfam database ( 24 ) , transcripts , genes and rna binding proteins , if available are also provided , as well as all relevant references ( not shown here ) . utrdb entries are also annotated for the occurrence of validated mirna targets , collected in mirecords ( 16 ) , a large , high - quality database of experimentally validated mirna targets resulting from meticulous literature curation . furthermore , we annotated a set of 3utr sequences that have a high likelihood to represent bona fide mirna target recognition sites , as predicted by the hoctar tool ( 17 ) . for a subset of seven organisms , namely human , mouse , rat , cow , dog , chicken and arabidopsis , for which a suitable genome assembly is available for such species we were able to clean all redundancies based on the observation of coincident utrs coordinates , arising from alternative mrna isoforms . these include : ( i ) highly conserved sequence blocks from the 17-way phastcons vertebrate conserved elements ( 18 ) ; ( ii ) significantly conserved tracts detected by evofold ( 19 ) ; and ( iii ) structural conserved non - coding rnas detected by rnaz ( 20 ) . phastcons detects evolutionarily conserved elements using a genome - wide multiple alignment based on a phylogenetic hidden markov model ( 21 ) . evofold is a general comparative genomics method based on phylogenetic stochastic context - free grammars for identifying rna secondary structures encoded in the human genome and conserved in an eight - way genome - wide alignment of the human , chimpanzee , mouse , rat , dog , chicken , zebrafish and pufferfish genomes ( 19 ) . rnaz evaluates conserved genomic dna sequences for signatures of structural conservation of base pairing patterns and exceptional thermodynamic stability . we employed three sets retrieved from ( 20 ) , with regions conserved with p - value > 0.9 in human , mouse , rat and dog ( set 1 ) ; human , mouse , rat , dog and chicken ( set 2 ) ; in human , mouse , rat , dog , chicken and either fugu or zebrafish ( set 3 ) . to assess the completeness of 5utrs in human and mouse we used the mapping data of the cage tags indicating the location of the transcription start site ( 22 ) . the 5-end of a 5utr has been considered as complete when at least five cage tags map in a nearby position ( a window of 5 bp around the mapping position of the 5-end of the 5utr ) . analogously , a 3utr is considered complete at its 3-end if a polya signal and/or a polya tail is detected in the original transcript sequence . the utrdb and utrsite data have been organized into relational databases using mysql as the database management system . a novel implementation detail in this new release is that several physical databases ( containing utr sequences and annotations from refseq and aspicdb transcripts , chromosome coordinates of source transcripts for the seven model organism , taxonomic data , etc . ) the new search and retrieval system retrieves and integrates data contained in these different relational databases to give out the requested data on utrs and related annotations [ such as the database from which a utr was recovered ( refseq or aspicdb ) , genomic coordinates and structure , mirna targets and conserved elements localization , functional elements , etc . ] . genomic information and features and annotation sections report information on genome mapping coordinates and on the localization of utrsite elements , mirna targets and conserved elements , respectively . the genomic information and features and annotation sections report information on genome mapping coordinates and on the localization of utrsite elements , mirna targets and conserved elements , respectively . utrdb ( utref section , release 2010 ) contains a total of 473 330 5utr and 527 323 3utr entries , respectively , from 483 605 genes in 79 species ( see the supplementary data for more information ) . a total of 788 370 utrsite motifs are annotated ( 317 767 in the 5utrs and 470 603 in the 3utrs ) , 20 191 experimentally validated mirna targets , and 242 773 conserved regions . for human , the utrfull section is also available , including utrs deriving from full length transcripts collected in aspicdb ( 7 ) . overall , utrfull contains 124 345 and 194 503 5 and 3utrs respectively ( 3.37/gene ) and 3utrs ( 5.18/gene ) , with 348 412 annotated utrsite motifs , 649 679 conserved elements and 105 209 experimentally validated mirna targets . utrdb and utrsite are accessible through a newly developed retrieval system where simple and advanced search forms are available . additionally , the advanced form permits a further refinement of the utr subset to be retrieved using several criteria including the number of cage mapping tags ( for 5utrs ) , the length of the utr , the number of spanning exons , the occurrence of utrsite motifs , conserved elements and mirna targets . the utrscan feature allows the enquirer to search user - submitted sequences for any of the motifs collected in utrsite . ministero dellistruzione , delluniversit e della ricerca , italy : fondo italiano ricerca di base , italy : laboratorio internazionale di bioinformatica ( libi ) ; laboratorio di bioinformatica per la biodiversit molecolare ( mblab ) .

the 5 and 3 untranslated regions of eukaryotic mrnas ( utrs ) play crucial roles in the post - transcriptional regulation of gene expression through the modulation of nucleo - cytoplasmic mrna transport , translation efficiency , subcellular localization and message stability . utrdb is a curated database of 5 and 3 untranslated sequences of eukaryotic mrnas , derived from several sources of primary data . experimentally validated functional motifs are annotated and also collated as the utrsite database where more specific information on the functional motifs and cross - links to interacting regulatory protein are provided . in the current update , the utr entries have been organized in a gene - centric structure to better visualize and retrieve 5 and 3utr variants generated by alternative initiation and termination of transcription and alternative splicing . experimentally validated mirna targets and conserved sequence elements are also annotated . the integration of utrdb with genomic data has allowed the implementation of an efficient annotation system and a powerful retrieval resource for the selection and extraction of specific utr subsets . all internet resources implemented for retrieval and functional analysis of 5 and 3 untranslated regions of eukaryotic mrnas are accessible at http://utrdb.ba.itb.cnr.it/.

unfortunately , electrical injury can result in some of the most devastating thermal traumas . as opposed to thermal burns , the cutaneous burn size does not correlate with the extent of damage seen in highvoltage ( > 1000 v ) electrical injuries ; electrical injuries result in extensive deep tissue injury in addition to various other systemic complications . morbidities , prolonged hospital stay , multiple visits to the operating room , and long rehabilitation process are not uncommon with these types of injuries . a 47 year - old caucasian male , working as an electric company linesman , was transferred to the montreal general hospital following a workrelated high - voltage electrical injury ( hvei ) . while working near high tension power lines , he lost balance and accidently grabbed hold of a wire running 14,000 v with both hands . he was subsequently thrown from the source , fell approximately twenty feet , and suffered blunt head trauma resulting in loss of consciousness . he had 3% visible total body surface area burns involving bilateral wrists circumferentially and bilateral hands ( fig . this consisted of third degree burns to the volar aspects of both wrists , and second degree burns to the dorsal aspects of both wrists and hands with digits and palms relatively sparred . ct scan of the head revealed a left frontal bone comminuted fracture and a left subdural hematoma with a 3 mm shift . the patient was immediately taken to the operating room by the neurosurgery team for left frontal craniectomy . images a & b show the volar aspects of the left and right wrists , respectively . images c & d show the burns extending onto the dorsal surface of the left and right hand , respectively . within hours of presentation , he was found to have elevated compartment pressures in both hand ( 100 and 70 mmhg on the right and left , respectively ) and wrists ( 91 and 75 mmhg on the right and left , respectively ) and was immediately taken to the operating room for bilateral hand and wrist escharotomies and fasciotomies ( fig . 2 ) . subsequently the patient was taken back to the operating room for serial debridements of necrotic tissue . imaging had shown extensive tissue necrosis extending from the distal third of the forearm to the level of the wrists bilaterally , involving both extensor and flexor compartments ( fig . images a & b showing wrist fasciotomy , thenar incisions , and carpal tunnel release of left and right hands and wrists , respectively . images c & d show fasciotomy incisions on the dorsal aspect of left and right wrists , respectively , as well as the longitudinal metacarpal incisions of the hands . the image of left forearm demonstrates the extensive non - enhancing muscles from the distal third of the forearm to the level of the wrist suspicious for myonecrosis involving both extensor and flexor muscles . despite escharotomies , fasciotomies and serial debridements the patient 's left hand became progressively congested with poor doppler signals and low o2 saturation within each digit . on postburn day 16 , 9 days since the last debridement , the hand became cold and did not return blood on pinprick in any of the digits . later that night , the patient was taken to the operating room for amputation of the left hand . after amputation , the patient was left with significant soft tissue defects to bilateral wrists and hands . bilateral pedicle groin flaps were used for coverage of the defects as well as to increase vascularity to the region ( fig . fourteen to twenty - one days after inset of the flaps , the flaps were ready to be separated ; final results are shown in fig . 4b and fig . image a shows the patient with bilateral pedicle groin flaps attached to bilateral wrists . the patient remained in hospital for a total of 81 days , 65 of which were spent in the icu . he was taken to the operating room a total of 7 times for escharotomies , fasciotomies , and serial debridements of bilateral hands and wrists , as well as amputation of his left hand and the necessity of tissue transfers , in the form of pedicle groin flaps , for soft tissue coverage . his course was complicated by rhabdomyolysis with a creatine kinase level peaking at 52 235 u / l , which was successfully managed with copious intravenous hydration and diuresis . the patient is currently rehabilitation center , working extensively with physiotherapy for elbow and shoulder mobility . it is reported that electrical burns constitute between 0.04% to as high as 32.2% of admissions to major burn centers ( 1 , 3 - 6 ) . mortality rates are significant with these types of injuries , reported in the literature to be as high as 59% ( 1 ) ; the most common cause being secondary to an acute arrhythmia at the scene of the injury(2 ) . they account for approximately 1000 deaths each year in the united states alone , ranking 5th as the most common cause of occupational deaths ( 3 ) . electrical burns are most commonly seen in work related injuries and involve mainly young males . electrical company linesman , electricians and construction workers are especially at risk ( 4 , 5 ) . sadly , it has been reported that as little as 5.4% of patients suffering a hvei are able to return to their previous line of work ( 2 ) . this can likely be attributed to the fact that these injuries commonly involve the hands and upper extremity ( 4 , 5 ) . contrary to thermal burns , high - voltage injuries result in extensive deep tissue damage , extending far beyond what can be predicted by tbsa involved , and resulting in higher rate of complications ( 6 ) . in a case - matched controlled analysis comparing hvei and thermal burns , handschin et al . ( 6 ) found a significantly higher rate of escharotomy/ fasciotomy ( 47% vs. 21% ) , amputations ( 19.1% vs. 1.5% ) , as well as total hospital length of stay ( 44 days vs. 31 days ) in hvei versus thermal burns . commonly seen with hvei are associated acute injuries which include fractures , head trauma , intra - abdominal injury , renal injury , soft - tissue injury , and acute ocular injury . associated injuries have been described to occur in 25.1% of hvei ( 5 , 8) . in addition to associated trauma , patients suffering hvei are prone to various complications as well . in a study involving 202 electrical injuries , neurologic complications , deep muscle involvement , and amputation of extremities similarly , arnoldo et al . found amputation of extremities or digits and muscle necrosis to be some of the most frequently observed complications , observed in 95 and 68 of the 263 cases of hvei , respectively ( 5 ) . as presented in our case , myoglobinuria and fasciotomy are also commonly encountered complications . in the current literature , escharotomy / fasciotomy rates have been described to be as high as 54% ( 7 ) and amputation rates as high as 49.4% ( 2 ) . furthermore , they had found myoglobinuria and the need for fasciotomy to be independent risk factors for amputation . using an equation derived to predict the probability of amputation ( 8) , the prognosis for these patients depends on the degree of the initial insult as well as the severity of any subsequent complications . early intervention is the goal with resuscitation and aggressive surgery being the mainstay of management . considering that most hvei are work - related , the best way to decrease the morbidity and mortality related to these injuries is prevention . through public education and work safety programs ,

electrical burns are among the most devastating of burn injuries . high voltage electrical injuries result in extensive deep tissue damage and are associated with multiple complications , long term morbidity , and a high mortality rate . we describe the case of a 47 year - old electric company linesman who suffered a high voltage electrical injury ( hvei ) of 14,000 volts to bilateral hands and wrists managed by the division of plastic and reconstructive surgery at the mcgill university health center in montreal , quebec , canada . his management included multiple operative procedures , including escharotomies , fasciotomies , serial debridements , and bilateral pedicle groin flaps , and amputation of his left hand .

previously , pain has been underestimated and undertreated in children , due to individual and social attitudes toward pain and the complexity of its assessment in children [ 13 ] . over the past decade , the importance of pain control in the pediatric population has been more widely recognized , especially as outpatient procedures have been performed with increasing frequency ; they currently constitute 60% to 70% of operative procedures conducted in north america . although no population - based data examining practice patterns of postoperative analgesia after ambulatory pediatric general surgical procedures exist , the current standard at many institutions is to provide a prescription for opioids , frequently oral acetaminophen plus codeine or oxycodone for analgesia after outpatient surgery . nonsteroidal anti - inflammatory drugs ( nsaids ) have been widely studied and are proven to be effective analgesics for postoperative pain control [ 5 , 6 ] . unfortunately , no prospective trials have examined the combination of acetaminophen plus nsaids compared with acetaminophen plus narcotics in outpatient pediatric surgery procedures . at the community - based children 's hospital where this study took place , the objective of this study was to compare the efficacy of acetaminophen / ibuprofen ( nonnarcotic ) or acetaminophen plus codeine or oxycodone ( narcotic ) for management of pain in children undergoing laparoscopic appendectomy on a rapid discharge protocol . after institutional review board ( irb ) approval , a prospective trial was carried out to evaluate postappendectomy pain control , comparing nonnarcotic to narcotic medications . individual consents and assents for this study healthy children in the american society of anesthesia ( asa ) risk classes 1 and 2 undergoing laparoscopic appendectomy at the community - based children 's hospital using a rapid discharge protocol between july 1 , 2010 and march 30 , 2011 were enrolled in the study . children having any additional procedure(s ) at the time of the appendectomy , those with chronic medical issues ( asa class 3 or higher ) or developmental delays , patients with allergies or contraindications to study medications , and those receiving chronic treatment with opioids or nsaids were excluded . children were divided based on clinical practice patterns , as two surgeons in a four - person faculty group employed the nonnarcotic regimen , while the other two routinely used narcotics . the nonnarcotic group received 15 mg per kg of acetaminophen every 4 hours as needed plus 10 mg per kg ibuprofen every 6 hours around the clock ( atc ) for 48 hours and then every 6 hours as needed , while the narcotic group received 10 mg / kg acetaminophen plus 1 mg / kg codeine or oxycodone every four hours as needed for pain . during the course of the study parents were agreeable to the pain management treatment regime utilized by their child 's surgeon and there were no instances of parents requesting alternate pain treatment methods . at the time of the postoperative visit , parents were asked to document days of medication use and time needed for return to normal activity . due to the high potential for subjectivity , pain scores student 's t - test and fisher 's exact test were used for statistical analysis . a total of 251 children , ranging in age from 2 to 19 years , underwent appendectomy over the nine - month study period . two hundred fifteen patients had the presumed diagnosis of acute simple appendicitis and proceeded to surgery . the remaining 36 patients underwent interval appendectomy after medical management for perforated disease ( 15 of these had an exposed fecalith or residual abscess cavity and were admitted to postoperative intravenous antibiotics , while 21 underwent uncomplicated procedures and were eligible for expeditious discharge and inclusion in the pain control study ) . of the 215 that proceeded to surgery for laparoscopy , gangrene or perforation was noted in 29 patients ( these children were admitted to antibiotics postoperatively and excluded from further study ) . of the 207 , the single - port , single - instrument transumbilical approach was used in 198 patients ( 96% ) . there was no difference in demographics and operative details when comparing children who received narcotics with those who did not ( table 1 ) . ninety - seven percent of the parents of children in the nonnarcotic group stated that the pain was controlled by the prescribed medication , compared to 90 percent in the narcotic group ( table 2 ) . in the past , effective pain alleviation in the pediatric field was often inadequate due to the misimpression of medical personnel and caregivers that analgesic drugs were harmful [ 9 , 10 ] and that pain reception was muted in the young . analgesia appropriate for the intensity of suffering should be provided both in the hospital setting and at home . of late , more emphasis has been placed on the assessment and treatment of noxious stimuli in the practice of pediatrics , and the study of relief of pain in neonates , infants , and children has moved to the forefront [ 1 , 2 ] . the goal of the present trial was to examine the efficacy of nonnarcotic versus narcotic regimens in postoperative pain control after laparoscopic appendectomy in children . surprisingly , our work demonstrated that nonnarcotic medication was at least as effective as the stronger , opioid - based therapy ( table 2 ) . the discomfort associated with any abdominal surgery is sufficiently severe to merit postsurgical analgesia . because different procedures may induce incomparable levels of pain , we focused on a single operation in a prospectively observed setting children on a rapid discharge pathway after appendectomy to control both operative and postoperative variability , lending credibility to the comparison between the nonnarcotic and the narcotic therapy . there was statistical difference in parents ' satisfaction , who favor the nonnarcotic therapy in this study . of note , in the nonopioid regimen , ibuprofen was recommended around the clock immediately following operation , not as needed . although widely used by surgeons , as - needed administration of analgesia appears , in randomized trials , to be substandard when compared to regular dosing after ambulatory surgery . in conclusion , nonnarcotic therapy when compared with narcotic therapy did not provide inferior analgesic , and it was associated with a higher parental satisfaction . this study failed to show any evidence to support the widespread use of opioids in children in the settings of early discharge after appendectomy . it would be reasonable to suspect that this regimen could be applied successfully in a range of outpatient procedures . the results of this trial suggest that a safe , effective , and inexpensive strategy for outpatient analgesia is a combination of acetaminophen and ibuprofen , a treatment option that avoids the possible complications of opioid use .

purpose . to compare narcotic versus nonnarcotic outpatient oral pain management after pediatric laparoscopic appendectomy . methods . in a prospective study from july 1 , 2010 , to march 30 , 2011 , children undergoing laparoscopic appendectomy on a rapid discharge protocol were treated with either nonnarcotic or narcotic postoperative oral analgesia . two surgeons in a four - person faculty group employed the nonnarcotic regimen , while the other two used narcotics . days of medication use , time needed for return to normal activity , and satisfaction rate with the pain control method were collected . student 's t - test was used for statistical analysis . results . a total of 207 consecutive children underwent appendectomy for acute , nonperforated appendicitis or planned interval appendectomy . the age and time to discharge were equivalent between the nonnarcotic ( n = 104 ) and narcotic ( n = 103 ) groups . both had an equivalent number of medication days and similar times of return to normal activity . ninety - seven percent of the parents of children in the nonnarcotic group stated that the pain was controlled by the prescribed medication , compared to 90 percent in the narcotic group ( p = 0.049 ) . conclusion . this study indicates that after non - complicated pediatric laparoscopic appendectomy , nonnarcotic is equivalent to narcoticbased therapy for outpatient oral analgesia , with higher parental satisfaction .

studies have shown that the early detection of breast cancer leads to better patient prognosis and a greater five - year survival rate . diagnostic and prognostic markers play a key role in classifying tumors and determining the best treatment plan for a patient . the most widely used and established prognostic markers for breast cancer recurrence are tumor size , tumor grade , lymph node involvement , and tumor hormone receptor status . these indicators , although well established , are all related to tumor aggressiveness . recent evidence has shown that proliferation markers , such as ki-67 and proliferating cell nuclear antigen ( pcna ) , may have independent prognostic value [ 13 ] . although these proliferation markers have potential , recent studies indicate that thymidine kinase 1 ( tk1 ) , another marker associated with proliferation , may be a better prognostic marker than either ki-67 or pcna [ 4 , 5 ] . thymidine kinase 1 ( tk1 ) has been studied extensively , primarily as a diagnostic biomarker for a variety of cancer types . tk1 is a nucleotide salvage pathway repair enzyme that is primarily responsible for the phosphorylation of thymidine to thymidine monophosphate . tk1 is associated with proliferating cells and is primarily elevated during s phase [ 6 , 7 ] . as a biomarker , higher serum tk1 activity levels correlate with a more advanced cancer stage and grade [ 810 ] . serum tk1 levels also show prognostic potential as their levels help predict future relapse at the time of primary diagnosis in breast and colorectal cancer patients [ 11 , 12 ] . one study demonstrated that breast cancer patients who later showed recurrence initially had higher primary tumor tk1 levels when compared to those patients who did not show recurrence . furthermore , breast cancer patients with either high or intermediate tk1 activity in their tumors showed rapid disease progression and poorer prognosis as compared to patients with low tk1 activity in their tumors . tumor tk1 levels , similar to serum tk1 levels , also correlate with both stage and grade . although there is a significant correlation between pcna and tk1 staining of breast cancer tissue , tk1 showed a significant correlation with stage and grade while pcna did not , indicating that tk1 might be a more accurate marker for diagnosis and prognosis . similarly , there is a significant correlation between ki-67 and tk1 in breast cancer tissue when compared to normal tissue ; however , due to early upregulation of tk1 as compared with ki-67 , tk1 may be a more accurate prognostic marker [ 16 , 17 ] . tk1 upregulation as an early event of cancer is a novel concept that has been addressed by only a few recent studies . one such study involving a health screening of 8,135 people found that 89.2% of persons with elevated serum tk1 levels had diseases linked to risk for pre-/early cancerous progression , including one individual who developed liver carcinoma 13 months after the health screening . similar studies have also shown that recurrence can be detected by elevated serum tk1 levels as early as 16 months before the clinical onset of relapse . this study seeks to determine whether , similarly to serum tk1 , tumor tk1 upregulation is an early event in tumor development and may aid in the identification of precancerous tissue . tissue arrays containing tissue from normal ( n = 56 ) , adenosis ( n = 22 ) , and breast carcinoma ( n = 97 ) patients as well as a progressive breast array ( cybrdi inc . , frederick md ) were analyzed for tk1 expression . breast carcinoma tissue included simple carcinoma ( n = 30 ) , infiltrating duct carcinoma ( n = 41 ) , medullary carcinoma ( n = 12 ) , scirrhous carcinoma ( n = 11 ) , and infiltrating lobular carcinoma ( n = 3 ) . tissue arrays were stained using an anti - tk1 mouse monoclonal antibody ( cb001 ) , which we previously demonstrated to be highly specific to tk1 . using this antibody , briefly , formalin - fixed paraffin - embedded specimens were prepared by deparaffinization and rehydration . to retrieve antigenicities of tk1 , specimens were boiled in 0.01 m sodium citrate buffer ( ph 6.0 ) for 12 minutes and allowed to cool at room temperature for 20 minutes . the endogenous peroxidase activity was blocked by immersion in 3% h2o2 in methyl alcohol at room temperature for 20 minutes . the slides were then washed in phosphate - buffered saline ( pbs ; ph 7.2 ) and blocked in 10% normal horse serum for 30 minutes . after blocking , the slides were incubated at room temperature for 3 hours with either anti - tk1 mouse monoclonal antibody ( diluted 1 : 100 ) or isotype control ( 0.6 g/l , mouse igg , upstate company , 12 - 371 ) . slides were washed with pbs and then incubated with a biotin - conjugated anti - mouse secondary antibody ( abc kit , vector lab inc . ) at room temperature for 30 minutes . after pbs washing , slides were incubated for 30 minutes , at room temperature , with streptavidin - peroxidase ( abc kit , vector lab inc . ) and then washed again in pbs . diaminobenzidine ( vector lab inc . ) was used as a chromagen , and the slides were counterstained with haematoxylin . specimens were scored by three pathologists , and a consensus score of positive , weak positive , or negative was compiled . a positive score indicated cytoplasmic staining of tk1 in 525% of tumor cells . if some signal was detected but was insignificant when compared to the isotype control , it was given a weak positive score . a chi - square test of independence was applied to compare the scores of normal and malignant tissues . due to the limited number of cases in the progressive breast array , no statistical analysis on this array differences with p < 0.05 ( two - sided ) were regarded as statistically significant . tk1 expression was found to be significantly different ( p < 0.001 ) between normal breast and breast carcinoma tissue . a total of 73 breast carcinoma tissues ( 79% ) were positive for tk1 expression while only 18 normal breast tissues ( 36% ) scored positive . breast tissue was also stained using an isotype control ( mouse igg , upstate company ) , and all breast tissue was found to be negative . since these normal tissues were retrieved from the margins around a tumor and were considered pathologically normal , we sought to determine if tissue from noncancerous individuals yielded similar results . interestingly , there was no tk1 staining in any breast tissue obtained from noncancerous individuals , called fda - approved true normal tissue ( data not shown ) . therefore , these 18 tk1 positive normal tumor margins may not be false - positive results , but rather precarcinoma tissue , which is considered pathologically normal tissue by current standards . tk1 expression was also found to be significantly different ( p = 0.013 ) between the different types of breast carcinoma tissue . a chi - square test of independence was applied to compare the scores of the various types of breast carcinoma tissue . the pearson chi - square value was 22.452 , using 10 degrees of freedom , and the two - sided p - value was 0.013 . the results are summarized in table 1 and typical staining can been seen in figure 1 . in summary , infiltrating lobular carcinoma and scirrhous carcinoma tissues all stained positive for tk1 , while 6683% of simple , infiltrating duct , and medullary carcinoma tissues stained positive for tk1 . further studies with larger sample sizes may further elucidate the differences between these tissue types . in addition to the tk1 positive breast carcinoma tissues , 4 breast adenosis tissues ( 22% ) were also found to be positive for tk1 expression . these 4 positive precancerous tissues were the first indication that tk1 expression may be an early event in tumor development . to pursue this hypothesis , we obtained a progressive breast array . this progressive breast array included tissue from different tumor developmental stages , such as normal , adenosis , and atypical hyperplasia , moderate atypical hyperplasia , severe hyperplasia , nonspecific infiltrating duct carcinoma , infiltrating lobular carcinoma , and infiltrating duct carcinoma with lymph node metastasis . the results are summarized in table 2 and typical staining can be seen in figure 2 . the proliferating epithelial cells of some cases of breast adenosis were positive for tk1 expression as well as breast tissue with simple or atypical hyperplasia . as previously seen , most breast carcinoma tissues were also positive for tk1 expression while no breast tissue stained positive with an isotype control . it appears from this progressive array that since tk1 is found in precancerous tissue , tk1 upregulation is an early event in breast tumor development . these results support the previous conclusion that in some cases , there may be a difference between true normal tissue from noncancerous patients and the pathologically normal tumor margins . further studies are needed to elucidate the differences between both the normal tumor margins and precancerous tissues that were positive for tk1 and those that were negative . perhaps , the prognostic value of tk1 may be of help in identifying those precancerous tissues which are of greatest risk to the patient . therefore , tk1 expression is an early event in tumor development and may aid in the identification of precancerous tissue . the aim of this study was to determine if tk1 upregulation is an early event in tumor development . from the progressive breast array , it can be seen that in many cases of breast cancer , tk1 is upregulated in precancerous tissue and remains elevated in correlation to cancer stage . although not elevated in all tumors , tk1 appears to be upregulated as an early event in most tumors and therefore can possibly be used in connection with other diagnostic and prognostic techniques to improve patient outcome . these results also indicate that the tk1 positive pathologically normal tumor margins may in fact be tumor cells that have escaped pathological identification . this preliminary research may indicate that tk1 can be used to identify possible malignant cells , which have evaded pathological detection during surgical removal . unfortunately due to the anonymity of these patient samples , we have been unable to determine if tk1 positive tumor margins are of clinical significance . further research would be required to establish if these tk1 positive cells are in fact a result of the tumor tissue . overall , it appears that tk1 has diagnostic and prognostic potential in identifying breast tumor tissue as well as precancerous tissues . the ability to identify tumor tissue during the early stages of development is of significant value . therefore , the histological identification of tumors utilizing tk1 suggests promising prognostic and diagnostic potential in breast cancer tissue .

prognostic markers play an important role in our understanding of tumors and how to treat them . thymidine kinase 1 ( tk1 ) , a proliferation marker involved in dna repair , has been shown to have independent prognostic potential . this prognostic potential includes the novel concept that upregulation of serum tk1 levels is an early event in cancer development . this same effect may also be seen in tumor tissue . in order to demonstrate that tk1 upregulation is an early event in tumor tissue formation , tissue arrays were obtained and stained for tk1 by immunohistochemistry . using a progressive breast tissue array , precancerous tissue including breast adenosis , simple hyperplasia , and atypical hyperplasia stained positive for tk1 expression . different stages of breast carcinoma tissue also stained positive for tk1 including nonspecific infiltrating duct , infiltrating lobular , and infiltrating duct with lymph node metastasis carcinomas . this indicates that tk1 upregulation is an early event in breast carcinoma development , and may be useful in identifying precancerous tissue . further work is needed to better understand the differences seen between tk1 positive and negative tissues .

cutaneous squamous cell carcinoma ( scc ) is the second most common type of non - melanoma skin cancer . in general , the management of cutaneous scc depends on its tumor stage . however , concerning high - risk patients or tumors on the cosmetic areas , the management of cutaneous scc differs in each case [ 1 , 2 ] . though no standard treatment for cutaneous scc has been formulated , the therapeutic effects of several anti - cancer drugs , including bleomycin , have been reported [ 3 , 4 , 5 ] . in this report , we describe two cases of scc developing on the ear , for which complete remission was achieved with intra - arterial administration of peplomycin , a bleomycin derivative antibiotic , through a superficial temporal artery using an intravascular indwelling catheter . an 86-year - old japanese man visited our outpatient clinic with a 4-month history of a red nodule on his ear . on his initial visit , physical examination revealed a red , dome - shaped , easy - to - bleed nodule with necrotic tissue on his right ear ( fig . a biopsy specimen revealed dermal infiltration of the tumor , which was composed of atypical keratinocytes with dyskeratotic cytoplasm ( fig . we screened for a possible internal malignancy with a ct scan but found none , except for slight swelling of a cervical lymph node . from the above findings , we diagnosed this patient as poorly differentiated scc , and for functional and cosmetic reasons , we selected intra - arterial administration of peplomycin through a superficial temporal artery using an intravascular indwelling catheter . we indwelled the point of the catheter at the feeding artery of the tumor by using indigo carmine ( fig . 1b ) , and continuously administered 5 mg of peplomycin per day intra - arterially for 12 days . four weeks after we finished the administration of peplomycin , the tumor mass had rapidly regressed , leaving a scar ( fig . a biopsy specimen revealed that no tumor cells remained at this time point ( fig . 2c , we added oral administration of 100 mg tegafur for 8 weeks , and there has been no sign of local recurrence or systemic lesions for 18 months . a 70-year - old japanese man visited our outpatient clinic with a 1-month history of a red nodule on his ear . on his initial visit , physical examination revealed a red , dome - shaped nodule with crust on his left ear ( fig . a biopsy specimen revealed dermal infiltration of the tumor , which was composed of atypical keratinocytes with dyskeratotic cytoplasm ( fig . we screened for possible internal malignancy with a ct scan but found none . from the above findings , we diagnosed this patient as well - differentiated scc , and for functional and cosmetic reasons , we selected intra - arterial administration of peplomycin through a superficial temporal artery using an intravascular indwelling catheter . three weeks after we finished the administration of peplomycin , the tumor mass had rapidly regressed , leaving a scar ( fig . 3b ) . a biopsy specimen revealed that no tumor cells remained at this time point ( fig . we added oral administration of 100 mg tegafur for 2 months , and there has been no sign of local recurrence or systemic lesions for 12 months . an 86-year - old japanese man visited our outpatient clinic with a 4-month history of a red nodule on his ear . on his initial visit , physical examination revealed a red , dome - shaped , easy - to - bleed nodule with necrotic tissue on his right ear ( fig . a biopsy specimen revealed dermal infiltration of the tumor , which was composed of atypical keratinocytes with dyskeratotic cytoplasm ( fig . we screened for a possible internal malignancy with a ct scan but found none , except for slight swelling of a cervical lymph node . from the above findings , we diagnosed this patient as poorly differentiated scc , and for functional and cosmetic reasons , we selected intra - arterial administration of peplomycin through a superficial temporal artery using an intravascular indwelling catheter . we indwelled the point of the catheter at the feeding artery of the tumor by using indigo carmine ( fig . 1b ) , and continuously administered 5 mg of peplomycin per day intra - arterially for 12 days . four weeks after we finished the administration of peplomycin , the tumor mass had rapidly regressed , leaving a scar ( fig . a biopsy specimen revealed that no tumor cells remained at this time point ( fig . 2c , we added oral administration of 100 mg tegafur for 8 weeks , and there has been no sign of local recurrence or systemic lesions for 18 months . a 70-year - old japanese man visited our outpatient clinic with a 1-month history of a red nodule on his ear . on his initial visit , physical examination revealed a red , dome - shaped nodule with crust on his left ear ( fig . a biopsy specimen revealed dermal infiltration of the tumor , which was composed of atypical keratinocytes with dyskeratotic cytoplasm ( fig . we screened for possible internal malignancy with a ct scan but found none . from the above findings , we diagnosed this patient as well - differentiated scc , and for functional and cosmetic reasons , we selected intra - arterial administration of peplomycin through a superficial temporal artery using an intravascular indwelling catheter . three weeks after we finished the administration of peplomycin , the tumor mass had rapidly regressed , leaving a scar ( fig . 3b ) . a biopsy specimen revealed that no tumor cells remained at this time point ( fig . we added oral administration of 100 mg tegafur for 2 months , and there has been no sign of local recurrence or systemic lesions for 12 months . in this report , we describe two cases of scc on the ear successfully treated with intra - arterial administration of peplomycin through a superficial temporal artery . in addition to this selective chemotherapy , we administered oral tegafur , which achieved complete remission of the tumor . these findings suggest that the effect of intra - arterial administration of peplomycin with oral tegafur is one of the optimal therapies for the treatment of scc developing on the ear . recently , chitwood et al . reviewed the efficacy of topical or intralesional treatment of non - melanoma skin cancer . concerning scc , the cure rate of imiquimod is 76% for scc in situ ( 78/102 ) and 71% for invasive scc ( 5/7 ) . the cure rate of topical 5-fluorouracil is 61% for scc in situ ( 58/95 ) . in contrast to topical administration of drugs , the cure rate of intralesional administration of interferon alpha-2 ( ifn-2 ) for scc is 100% ( 3/3 ) , that of ifn-2b for scc in situ is 89% ( 8/9 ) and that of ifn-2b for invasive scc 89% ( 25/28 ) . these data suggest that the route for drug delivery is correlated with the clinical outcomes for the treatment of non - melanoma skin cancer . peplomycin is a bleomycin derivative antibiotic and its cytotoxicity toward mammalian cells is due to its ability to induce single- and double - strand dna breaks by the induction of g1-phase specific apoptosis [ 7 , 8 ] . for clinical application , peplomycin has recently been used as preoperative chemotherapy for scc in japan [ 3 , 4 , 5 ] . the total dose for conventional ways of peplomycin administration depends on its protocol ( 20110 mg , bolus injection of 510 mg / day ) [ 3 , 4 ] . though this reagent is useful for the treatment of scc , especially in combination with radiation or other cytotoxic drugs , the dose for the administration of this reagent is limited because of its dose - dependent fatal side effects , such as interstitial pneumonia [ 3 , 4 , 5 ] . therefore , an optimal method to keep a high concentration of peplomycin only in the tumor site is necessary . for the above reason , we selected intra - arterial , continuous administration of peplomycin through a superficial temporal artery for the treatment of cutaneous scc on the ear . indeed , in both of our two cases , the tumor mass decreased rapidly within 1 month . moreover , skin biopsy after the administration of peplomycin revealed that no tumor cells remained . in addition , we administered oral tegafur , which is generally used as adjuvant chemotherapy or combination chemoradiotherapy for scc in japan [ 9 , 10 ] . notably , a previous report also suggested that oral intake of tegafur after radical therapy significantly improves survival in cancer patients . therefore , in our present cases , we administered oral tegafur for the purpose of keeping the complete remission . since the additional administration of oral tegafur might have prolonged the tumor - free time in our two cases , our present cases suggest the possibility of continuous intra - arterial administration of peplomycin through a superficial temporal artery using an intravascular indwelling catheter for the treatment of cutaneous scc on the ear .

cutaneous squamous cell carcinoma ( scc ) is the second most common non - melanoma skin cancer and tends to develop in sun - exposed cosmetic areas , including the ear . in this report , we describe two cases of scc on the ear successfully treated with intra - arterial administration of peplomycin through a superficial temporal artery . in addition to this selective chemotherapy , we administered oral tegafur , which achieved complete remission of the tumor . these findings suggest that intra - arterial administration of peplomycin with tegafur is one of the optimal therapies for the treatment of scc developing on the ear .

microgastria is a very rare anomaly characterized by a small tubular stomach and is almost always associated with other congenital anomalies.1 to date , less than 100 cases of microgastria have been described in the literature.2 patients invariably encounter severe gastroesophageal reflux disease ( gerd ) due to the small reservoir capacity of the stomach and absence of esophagogastric angle of his . there have been various surgical procedures described as a choice of reconstruction for microgastria , including gastric augmentation with roux - en - y jejunal pouch anastomosed to the stomach , the hunt lawrence pouch.3 however , adequate control of gerd remains a concern in these patients.2 tegd first described as a salvage procedure for failed fundoplications in neurologically impaired children due to the high rate of failures of repeat operations in this group of patients,4 and can offer a superior solution to eliminate gerd . we present a patient with microgastria treated with tegd and esophageal jejunal anastomosis after a failed fundoplication . a male baby , born at term via a normal vaginal delivery presented at 3 weeks of age with dyspnea , poor feeding , and growth below the third percentile for weight for age . he was noted to have a ventriculoseptal defect ( vsd ) on echocardiography with moderate left to right shunting and a respiratory tract infection for which he received treatment . he was also noted to have a left preauricular sinus , a hypoplastic left thumb and radius , and abnormal left sacral hemivertebrae but chromosomal studies were normal . milk scan ( nuclear scintigraphy with technetium labeled formula feed ) and contrast study of the upper gastrointestinal tract demonstrated significant reflux with a suspected sliding hiatal hernia ( fig . 1 ) . there was no improvement of the infant 's general condition with various medical interventions , and at this stage , no suspicion of microgastria had been entertained . contrast swallow image at the age of 2 months demonstrating a distended distal esophagus with a small tubular stomach consistent with microgastria . initially , the findings were thought to show significant reflux with a suspected hiatal hernia . at 3 months , he was taken to operating room for an open antireflux procedure . a long tubular stomach was observed with insufficient fundus for nissen fundoplication and a decision was made to perform a partial anterior fundoplication.5 the spleen was thought to be mal - positioned . no hiatal hernia was observed . postoperatively , he was commenced on feeds but continued to show clinical signs of ongoing gastroesophageal reflux . fiberoptic esophagogastroscopy showed a reasonably snug wrap with the scope passing with ease , a tubular stomach and normal duodenum . in view of the recurrent respiratory tract infections , one of which required intensive care ward admission and ventilation , and ongoing reflux demonstrated on radiographic contrast studies , it was thought that the fundoplication procedure had failed . it was then decided to undertake a tegd at 7 months of age and 4 months after the initial operation . the esophagus was divided at the esophagogastric junction and the stomach fundus oversewn with 5/0 pds ( ethicon , somerville , new jersey , united states ) suture in a single layer . the vagal nerves were not preserved . a 35-cm roux - en - y segment of jejunum was passed posterior to the colon and stomach ( retrocolic - retrogastric ) and anastomosed primarily to the esophagus in an end - to - end fashion with 5/0 pds suture . a heine mikulicz pyloroplasty was also done to achieve adequate gastric emptying ( fig . e , esophagus ; pj , proximal jejunum ; ryj , roux - en - y segment of jejunum ; s , stomach ; tc , transverse colon ; tegd , total esophageal gastric dissociation . he was started on gradually increasing nasojejunal feeds once the contrast meal showed no hold up or reflux and no retrograde entry of contrast into the proximal gastroduodenojejunal arm of the roux - en - y loop . his respiratory symptoms had completely disappeared , and he had achieved a good recovery of all growth parameters with an age - appropriate diet tolerated without vomiting . at 4 years , 10 months of age , the latest follow - up showed his height and weight for age were both around 10th percentile ( 100.5 cm/15.5 kg ) . it has been described in patients as an isolated anomaly or in association with various degrees of limb - reduction ( amelia ) defects ; in association with the vacterl complex ( vertebral anomalies , anorectal malformations , cardiac , trachea esophageal fistula , renal agenesis , limb anomalies ) ; the pierre robin sequence ( micrognathia ) ; and in association with other foregut developmental anomalies such as asplenia , splenic malposition , and intestinal malrotation.1 6 7 8 treatment for microgastria - associated gerd has ranged from conservative expectant nonsurgical management to various forms of antireflux procedures with good long - term results being recorded from the hunt lawrence jejunal pouch to augment the stomach.1 3 6 9 10 11 since the first report of the hunt lawrence pouch for microgastria in 1980,11 several case reports have suggested such favorable outcomes compared with conservative treatments that early hunt lawrence pouch procedure is thought to be the choice of operation.10 however , in these reports , age - appropriate growth catch up was rarely achieved or otherwise nutritional support such as a feeding tube were needed.2 10 in addition , gerd remains a concern in these patients . tegd has been reported as achieving good outcomes not only as a salvage procedure for failed antireflux procedures in children with severe neurological impairment but as a primary antireflux procedure in those populations.4 12 13 14 15 gatti et al showed a marked reduction in reflux symptoms and an improved quality of life with tegd when compared with fundoplication in neurologically impaired patients.16 buratti et al suggested tegd be reserved only for repeated failed antireflux procedures.17 repeat operations , however , may pose a challenge due to multiple adhesions and numerous postoperative complications may be encountered . a primary procedure would thus be less challenging , with an equally good outcome . in their follow - up of 50 patients , lall et al showed a good outcome with a primary tegd despite some complications.15 upon review of the literature , we found at least two very similar cases in which the children with microgastria were treated by tegd.2 15 in these two cases , one child was able to tolerate all food orally and a gastrostomy used for supplementary feeding could be removed,2 and the other one had been able to eat normally without any food alternation or restrictions.15 most of the tegd published cases have included a gastrostomy in the procedure . we believe that microgastria cases without severe neurological impairment should not need a gastrostomy in the antireflux procedures . in fact , these patients have normal swallowing abilities that enable them to feed normally after the successful antireflux procedures . complications that have been associated with tegd include early anastomotic leaks , esophagojejunal anastomosis dehiscence , subphrenic collections , stricture formation , bowel obstruction from adhesions , dumping syndrome , and long - term nutritional and metabolic complications.15 17 in addition , a recent publication described esophagojejunal anastomotic stricture and gastric metaplasia as long - term complications after tegd in the patients with esophageal atresia repair.18 in our patient , we have not encountered any complications related to the surgery . the quality of life of patients post - tegd has been shown to be markedly improved with reduction of reflux symptoms as with our patient.2 6 furthermore , neurologically normal patients who underwent tegd , even with microgastria , were reported to be tolerating full oral feeds without symptoms of dumping.2 15 we present the long - term follow - up of tegd for microgastria . in our experience with this good result , we would suggest that tegd be added to the armamentarium of procedures that can be used in the treatment of microgastria . despite the high complication rates in redo operations reported in the literature , it may be the only effective antireflux surgery for recurrent microgastria - associated gerd . in addition , we suggest it can be explored as a primary treatment at the surgeon 's disposal in the treatment of microgastria - associated gerd . this report highlights microgastria - related reflux and a failed fundoplication who was treated with total esophageal gastric dissociation ( tegd ) resulting in an excellent outcome . we believe this is the first report revealing the long - term outcome of tegd being used in the treatment of microgastria .

microgastria is a very rare anomaly characterized by a very small tubular stomach that presents with severe gastroesophageal reflux disease due to the small reservoir capacity of the stomach . we present a patient with microgastria - related reflux and a failed fundoplication who was treated with total esophageal gastric dissociation ( tegd ) resulting in an excellent outcome . in our experience with this good long - term result , we would suggest that tegd be added to the armamentarium of procedures that can be used in the treatment of microgastria .

pentalogy of cantrell is a rare multiple congenital malformation which occurs worldwide with a reported incidence of 5.5 per million live births.1 the exact cause is not known but is mainly thought to be sporadic , though its being associated with some chromosomal disorders like trisomy 1823 and deletion on locus at xq25 - 26 has been described in some cases.4 it was first described by cantrell et al . , in 19585 with the pentad consisting of a giant omphalocoele and a supra - umbilical anterior abdominal wall midline defect , sternal cleft , ectopia cordis , intracardiac congenital malformations like ventricular septal defect , atrial septal defect and tetralogy of fallot , ventral midline diaphragmatic defect with defect of the diaphragmatic pericardim.5 other associated defects include cranial and facial anomalies , clubfeet , malrotation of the colon , hydrocephalus and anencephaly.67 pentalogy of cantrell often have a poor outcome which is dependent on the severity of the malformations.8 though some cases of pentalogy of cantrell had been reported in nigeria , its true prevalence is not known and none of those reported had been proven to completely fulfill the five main components of the pentad.91011 we , therefore , report a case of pentalogy of cantrell in a 9-month - old boy who completely fulfilled the diagnostic criteria . a 9-month - old boy was first seen at the age of 5 months being delivered with multiple congenital malformations involving the anterior abdominal and chest walls . the child was delivered at term gestation and at home ; the pregnancy was not adversely eventful and she had no antenatal care . however , the child has defect on the anterior abdominal wall with a huge swelling extending from the lower anterior abdomen to the lower anterior chest wall , which was pulsatile and covered by a thin membrane which was initially reddish at birth but later became thickened and darker following daily cleaning and dressing . there was no history of vomiting or constipation , child sucked directly from the breast , though interrupted occasionally to catch his breath , there was no history of difficulty with breathing and no darkening of the lips or mucous membrane . the mother was a 25-year - old stay at home mother with four other children in a non - consanguineous marriage ; she neither smoked cigarette nor drank alcohol and had no adverse medical record . , there was a big pendulous and pulsatile mass extending from slightly above the symphysis pubis to the epigastrum measuring 12 10 cm [ figure 1 ] with an epithelised membranous covering ; it had visible peristaltic waves , it was pundunculated , with cardiac pulsation felt in the epigastric region [ figure 2 ] . bowel and heart sounds were heard over the mass below the level of the diaphragm . he was not tachypneic or tachycardic and had first and second heart sounds with a systolic murmur . his chest x - ray showed a midline heart with inferior displacement [ figure 3 ] , abdominal ultrasound showed the swelling to contain loops of bowl and echocardiography revealed a 6 mm secundum atrial septal defect . the child is currently being followed up awaiting staged repairs of the defects . a bulge in the region of the epigastrium and lower sternum x - ray showing loops of bowl in the swelling with displacement of cardiac shadow pentalogy of cantrell is commoner in boys and less than 60 cases have been documented so far worldwide as at 2007.8 the exact mechanism is not completely understood , however , the proposed pathogenesis involves a defect in embryogenesis between 14 and 18 days after conception due to failure of the in folding of the lateral mesoderm . while most affected children die shortly after birth due to the severity of their defect ( especially the associated intra - cardiac defect and risk of infection in open defects ) , it has been reported in a 32-year - old - man.12 our patient was 9-month - old and remained active despite the associated atrial septal defect and has better prospect with adequately staged surgical intervention . our case had all the major features of the pentad , though with a relatively favourable lesion because the membrane of the giant omphalocoele was completely epithelised [ figure 4 ] and the peduncle covered with skin , which helped in preventing infection ; furthermore , the atrial septal defect was of moderate size and the child had remained stable , though he stands the risk of trauma to the barely covered heart , but with proper counselling the child has survived up till this age . the mass covered by thickened , hyperpigmented keratinised membrane pentalogy of cantrell can be diagnosed prenatally but that has not been the case in those reported from nigeria so far because lack of accessibility to a proper antenatal healthcare and for the fact that most of those diagnostic tools are not readily accessible to these low income parents . patients with complete expression of pentalogy of cantrell are rare and few may survive to older age depending on the severity of the associated lesions , more especially the intracardiac defect . furthermore , we advised that patients with giant omphalocoele should be thoroughly evaluated , because they may have an incomplete expression of the syndrome .

pentalogy of cantrell is a rare congenital malformation whose exact cause is not completely understood ; it is characterized by defects in the anterior abdominal and thoracic walls consisting of omphalocoele , diaphragmatic defect , ectopia cordis , intracardiac defects and sternal clefts . the complex has variable clinical expression with complete and incomplete expressions reported . we , therefore , report a case of complete manifestation of the pentad in a 9-month - old boy .

it began as a web interface for its predecessor , the genomic database acedb ( 1,2 ) . during the last half decade , it has been expanded to cover classical genetics and cell biology ( 3 ) , functional genomics ( 4 ) and the caenorhabditis briggsae genomic sequence ( 5,6 ) . new releases of wormbase are built every three weeks by amalgamating physical and genome sequence data from the c.elegans sequencing consortium ( sanger institute and washington university , st louis ) , genetic map data curated by the caenorhabditis genetics center ( university of minnesota and oxford university ) and diverse biological data curated by the wormbase consortium . every 10th release is maintained as a permanently available , stable data source ( freeze ) for reproducible bioinformatics . in the last year , the wormbase consortium has worked to make wormbase more reliably useful and stable , while continuing to add new biology and preparing to handle an expected five nematode genomic sequences in 2006 . much of wormbase is organized around two key data hubs , the gene page and the genome browser . both of these can summarize large amounts of data in a single view . however , as the contents of wormbase grew , the gene page became increasingly slow to load in users ' web browsers . we revised our software so that gene pages are pre - built and stored ready for use ; as a result , most gene pages now loaded in < 10 s. we also redesigned wormbase so that its software and data releases are packaged for easy uploading and updating . this allowed us to construct and maintain several mirror sites at the institute of molecular biology and biotechnology ( crete , greece ) , the california institute of technology , and the center for computational biology and bioinformatics ( daejeon , south korea ) . it also allows us to run wormbase on laptop computers for network - independent use and efficient software development . these improvements were made possible by clarifying internal data structures that are invisible to the user but critical for effective database management . for example , classical loci and coding sequences were consolidated into a single gene data object that can stably represent genes regardless of fluctuations in their classical or molecular names . we revised the genome browser display ( 7 ) so that different subsets of genomic data ( tracks ) , as well as different sections of the browser 's display framework , can be alternatively shown or hidden at the user 's option . this allows a user to construct economical and individualized views of any section of the genome , ranging in size from a few nucleotides to 1 mb in length . these views can be bookmarked as stable urls , or exported as publication - quality scalable - vector graphics images . protein motifs ( 811 ) now have their own data track , showing the domain organization of proteins in the context of intron / exon structure , interspecies conservation , single nucleotide polymorphisms ( snps ) , pcr reagents , rnai results and other genomic features . moreover , users can import and display their own data tracks seamlessly beside the core wormbase ones , either by uploading their own annotations from a local text file or by invoking a remote url ; using remote urls enables collaborative genomic analyses by multiple users sharing a common data repository . we developed textpresso , a tool for searching the full content of c.elegans articles for meaningful word relationships , and incorporated it into wormbase ( 12 ) . vector. we also added new terms to the drugs and small molecules and organism categories . the literature searchable by textpresso within wormbase contains 6259 full - text articles , including 5571 from the core c.elegans literature ; this body of literature is automatically updated and expanded every week . textpresso also contains 18 642 abstracts , including 8450 from international and regional c.elegans meetings . while textpresso was first designed for use by wormbase , it has proven useful to several other model organism databases ( e.g. and ) and is being extended to non - genomic disciplines ( such as neuroscience ; ) . textpresso has been made available to the generic model organism database software project ( ) as open source code . wormmart is a data warehousing system ( 13 ) that allows users to construct complex queries on wormbase and obtain results in html or tab - delimited text format . wormmart supersedes the batch sequences and batch genes reports , and facilitates arbitrarily complex queries such as find all genes in c.elegans that have an orthologue in c.briggsae , are located in chromosome iii , have reduced fertility in an rnai screen , and have annotated untranslated regions ( utrs). in addition to gene - centric queries , wormmart supports querying over - expression patterns , rnai phenotypes , mutant phenotypes , variations ( alleles ) and literature citations . wormmart is based on biomart ( ) , the core software driving the ensmart query engine at ensembl ( 13 ) . even for c.elegans , with a relatively compact and well - determined genomic sequence , it is a continuing challenge to detect the existence and correct structures of 21 600 genes ( 14 ) . in the past year approximately 5000 cdnas have been connected to protein - coding sequences , resulting in 948 more protein - coding sequences becoming completely confirmed by cdna data ( a 17.2% increase ) . essentially all c.elegans expressed sequence tag ( est ) and cdna sequences in public databases have been incorporated into wormbase gene structures . the number of introns identifiable from cdna sequences but absent from existing gene structures was lowered considerably ( from 746 to 121 ) . many other data besides cdna sequences were also used to identify correct gene structures : detailed studies from individual research papers , personal communications to wormbase staff , twinscan predictions ( 15 ) , sl1/2 ( 16 ) and tec - red sequences ( 17 ) , multiple alignments of protein families ( 18 ) , and c.briggsae homologies ( 5 ) . 5- and 3-utrs in wormbase are now automatically generated as part of full - length coding transcripts , taking into account additional data such as trans - spliced 5 leader sequences ( 16 ) and polyadenylation sites ( 19 ) ; 1800 new instances of trans - splicing have been identified . as originally published , c.elegans snps have often been inconsistent or incomplete : clone positions have changed over the years as sequence changes have been made , and published flanking sequences were often too short to uniquely map them to either clones or chromosomes . we thus went back through the original data and generated new flanking sequences that are unique in the genome . similarly , we remapped all rnai experiments , while adding two new large - scale datasets from an orfeome library - based rnai screen ( 22 ) and a full - genome rnai profiling of early embryogenesis ( 23 ) . this brought the total number of large - scale rnai data points in wormbase from 27 112 to 58 778 , and the number of distinct rnai phenotypes from 78 to 119 . the ws145 database release contained 2 984 398 microarray data points from 19 papers , describing 234 independent experiments , compared with 1 690 379 data points from 15 papers and 113 experiments from a year earlier . protein interaction and isolated promoter data : these currently include 5534 yeast two - hybrid interactions covering 15% of the c.elegans proteome ( 24 ) and 6538 promoter sequences cloned in the multisite gateway system ( 25 ) . molecular data become more useful when accompanied by human - readable , concise descriptions of gene function ( 26 ) . in wormbase , 3064/7864 ( 39% ) of genes that have been named ( i.e. , that are not simply anonymous , little - studied gene predictions ) now have such descriptions . for genes with at least one reference , 58% have concise descriptions ( 2421/4133 ) ; for genes with five or more references , 74% have concise descriptions ( 925/1248 ) ; for those with > 10 references , 76% have concise descriptions ( 635/839 ) ; with > 100 references , 86% have concise descriptions ( 85/99 ) ; and with > 200 references , 88% have concise descriptions ( 29/33 ) . thus , for those genes that are information - rich , we have 75% coverage with our concise descriptions . in addition , we are also annotating gene functions with structured , computationally tractable gene ontology ( go ) terms ( 27 ) . 5806 gene go term linkages have so far been identified , from data in 718 references . meanwhile , the entire genome has been scanned with automatic mappings to go terms from rnai phenotypes and from interpro domains ( 28 ) , yielding a total of 23 688 annotations . there is far more important biology of c.elegans than wormbase can expect to describe in a reasonable time by traditional approaches . we thus developed a new semi - automated annotation strategy and tested it by mass - extracting genetic interactions from the primary literature . a curator then read the individual sentences and identified individual gene gene interactions . in this way , 26 000 sentences were retrieved by textpresso from 4400 papers . from these , 10 000 interactions or possible interactions were identified , including : 5439 genetic interactions ( 54% ) ; 1820 non - genetic interactions ( 18% ) ; and 2739 possible interactions ( 27% ) . two encyclopedic volumes describing c.elegans biology were published in 1988 and 1997 ( 29,30 ) ; while still invaluable , both predate the last decade of research and the rise of functional genomics with web - based bioinformatics . wormbook is a new , online collection of original reviews on topics related to all aspects of c.elegans biology , as well as a repository for experimental protocols used by c.elegans researchers . wormbook provides a text companion to wormbase with contributions by > 100 expert biologists reviewing and synthesizing the facts presented in wormbase . when complete , wormbook will have hypertext links for genes , alleles , proteins and literature citations to wormbase and pubmed . conversely , researchers using these linked primary databases will have reciprocal access to wormbook , facilitating the exchange of ideas and promoting further research . over 20 completed wormbook chapters and > we anticipate that wormbase will be called upon to manage genomic sequences from multiple caenorhabditis species ( 31,32 ) . work on this began in 2005 with a gene set prediction for caenorhabditis remanei , in which several different gene prediction sets were generated , tested against c.elegans genomic and c.remanei est sequences , combined and hierarchically selected for the best possible automatic prediction . we also intend to expand the classical biological content of wormbase by systematically annotating mutant alleles with an extensive phenotype ontology ( 33 ) adopted for nematodes to allow better searches of gene function . we plan to make cells , cell groups and biological processes more significant entry points into the content of wormbase .

wormbase ( ) , the public database for genomics and biology of caenorhabditis elegans , has been restructured for stronger performance and expanded for richer biological content . performance was improved by accelerating the loading of central data pages such as the omnibus gene page , by rationalizing internal data structures and software for greater portability , and by making the genome browser highly customizable in how it views and exports genomic subsequences . arbitrarily complex , user - specified queries are now possible through textpresso ( for all available literature ) and through wormmart ( for most genomic data ) . biological content was enriched by reconciling all available cdna and expressed sequence tag data with gene predictions , clarifying single nucleotide polymorphism and rnai sites , and summarizing known functions for most genes studied in this organism .

hemimaxillofacial dysplasia ( hd ) was first recognized by miles et al . in 1987 in a report of two cases . this disorder has similar clinical manifestations as segmental odontomaxillary dysplasia ( sod ) but may demonstrate some degree of variable expressivity , for example , facial hypertrichosis is a variable finding . danforth et al . in 1990 reported a series of eight cases and named the condition . packota et al . in 1996 reported most common radiographic features of sod in a study of twelve additional cases . sod is an uncommon , nonhereditary developmental anomaly involving the maxilla , gingiva and dentition of the same arch . the prevalence of this condition is not well established since the literature largely consists of case reports . to date , 42 cases have been reported in the english literature . the diagnosis of sod is mainly based on clinical and radiographic presentation but may be augmented by histological findings . clinically sod is characterized by unilateral enlargement of posterior segment of maxilla , enlargement of gingiva , and ipsilateral dental anomolies . the age of the patient at presentation is variable but the condition is usually discovered during childhood with most common complaints being missing teeth , abnormal spacing , and delayed eruption . histologically , the affected bone consists of immature bone with irregular trabeculae of woven appearance with resting or reversal lines without osteoblastic or osteoclastic rimming . radiographically , vertically oriented trabeculae of woven bone is usually seen which results in a relatively radiopaque , granular appearance . on the affected side , a four - and - a - half - year - old male was referred to the department of pediatric dentistry by a general dental practitioner for evaluation of a painless left maxillary expansile lesion . the major concern was the delayed eruption of primary and permanent teeth in this quadrant . the patient was otherwise healthy with a noncontributory medical history . on clinical examination , the patient revealed mild facial asymmetry caused by an increase in fullness of the left upper lip and cheek . ipsilateral erythema with increased facial hair of the skin and a scar in the nasolabial region was also seen . intraoral examination demonstrated buccolingual expansion of maxillary left arch with gingival overgrowth since the age of 3 . his chief complaint was that of delayed eruption of his primary teeth in the same quadrant , especially in the canine and molar area . panoramic radiograph revealed lack of / delayed eruption of teeth with enlargement of the left maxilla ( figure 1 ) . cone beam computed tomography ( cbct ) was obtained to further study the osseous changes in the maxilla . trabeculation appeared to be ill defined , and generally oriented along the y - axis ( figures 2 and 3 ) . there was significant expansion of the left maxilla with involvement of the maxillary sinus along the inferior aspect . a clinical impression of fibro- osseous lesion such as fibrous dysplasia or juvenile active ossifying fibroma was made by the surgeon . the patient was subjected to general endotracheal anesthesia and an incisional biopsy of the left maxilla was done . the left maxilla appeared to have a grainy appearance with more normal appearing bone superiorly . histopathologic examination of the decalcified hard tissue revealed mostly woven bone with fibrous stroma , while some areas contained peculiar woven bone without fibrous stroma ( figure 4 ) . resting and reversal lines were noted . the histopathologic findings , in the context of clinical findings , led to a diagnosis of sod . based on the clinical , radiographic , and microscopic features , a diagnosis of sod was rendered . reassurance was provided regarding the benign nature of the condition and the patient was placed on periodic recall to monitor the growth and development of the maxillary bone and teeth . there was continued evidence of an expansile , hyperattenuating , well - defined lesion occupying the mid - left maxillary dentoalveolus . hemimaxillofacial dysplasia ( hmd ) was first recognized in 2 cases by miles in 1987 which is characterized by unilateral maxillary enlargement , gingival hyperplasia , facial asymmetry , ipsilateral dental abnormalities , unusual radiographic bone pattern , and facial hypertrichosis . danforth and melrose reported 8 cases in 1990 in which they termed sod due to lack of involvement of facial structures in these cases . described the criteria for the radiographic diagnosis of sod as sclerosis of bone with thickened trabeculae , missing premolars with delayed eruption of permanent teeth , vertical orientation of bony trabeculae , spacing between deciduous molars , and a small maxillary sinus on the affected side . our case features most of the criteria put forth by packota et al . . the acronym hats ( hemimaxillary enlargement , asymmetry of the face , teeth abnormalities , skin findings ) was introduced in 2004 by welsch and stein . the prevalence of this condition is not well established since the literature largely consists of case reports . according to a previous literature review , 27 cases of sod / hmd had been published from 1987 to 2000 [ 13 , 710 ] . the number of cases reported in the extant literature still remains variable since not all cases are well documented . we present the most common clinical features , radiologic features , and cutaneous findings ( tables 1 and 2 ) [ 118 ] for a total of 43 cases including this case . clinically , sod usually presents as a non - progressive facial asymmetry , ipsilateral gingivo - dento - alveolar maxillary involvement which can extend from the canine to tuberosity area . radiographically , sod shows ill - defined bony sclerosis with thickened and coarse bony trabecular pattern . osseous involvement demonstrates the presence of thick trabeculae of immature woven bone with prominent reversal and resting lines , noninflammatory fibrous stroma with lack of osteoblastic and clastic activity . sod may go unrecognized or misdiagnosed because some conditions like fibrous dysplasia and regional odontodysplasia ( rod ) shows similarities to sod , but they can be differentiated from sod ( table 3 ) . in addition , rod does not demonstrate unilateral enlargement of the gingiva and associated alveolar ridge and usually affects permanent anterior teeth only . in addition , rod does not demonstrate unilateral enlargement of the gingiva and associated alveolar ridge . fibrous dysplasia and sod have similar radiographic features but fibrous dysplasia is not noted for absence of teeth . although fibrous dysplasia ( fd ) often is associated with a similar clinical expansion of the alveolar ridge , the radiographic and histopathologic features are very different . upon imaging , craniofacial fd presents as an ill - defined zone of fine trabeculation which contrasts very clearly with the course trabecular pattern noted in sod . histopathologically , immature fibrous dysplasia presents with irregular trabeculae of vital woven bone which resembles chinese characters , does not demonstrate numerous reversal lines , and typically reveals significant osteoid rimming . treatment of sod remains unknown as the management protocol in most case reports has not been discussed to date . once diagnosed , sod seems to remain stable and may or may not require surgical intervention . so the primary goal of the treatment is to retain the deciduous teeth , thus facilitating eruption of the permanent teeth so that occlusion can be restored . standard of care is close observation with most clinicians performing limited recontouring in cosmetically objectionable cases . the lack of reports in adults suggests the possibility of spontaneous regression with age . in our case , but it is important to recognize the existence of the condition and diagnose it using appropriate clinical and radiographic findings . even though sod is a rare entity , the radiologist must consider sod in the differential diagnosis of entities such as monostotic fibrous dysplasia , regional odontodysplasia , hemifacial hyperplasia , and gingival fibromatosis . the clinical and radiological features of sod are well described but the condition is probably underreported due to misdiagnosis . since it affects children care should be taken to accurately diagnose the condition to reassure the patient and offer the best treatment options . treatment may be limited to retaining the primary teeth and enhancing the eruption of the permanent teeth , if possible , to restore occlusion in that quadrant .

segmental odontomaxillary dysplasia ( sod ) is an uncommon , nonhereditary , recently recognized developmental disorder affecting the upper jaw and related dental components . it is a rare condition of uncertain etiology that results in painless unilateral expansion of the posterior dentoalveolar complex , gingival hyperplasia , lack of one or both premolars in the affected area , delayed eruption of adjacent teeth and malformations of the primary molars . radiographically , the affected bone is thickened and irregular in outline , with coarse trabecular pattern that is vertically oriented resulting in a relatively radiopaque granular appearance . only a few cases have been reported in the english literature . considering the rarity of the condition , we report a case of sod in a pediatric patient who was followed up over a period of over two years . the clinical , radiographic , and histologic features are presented along with a review of the literature .

atherosclerotic renal artery stenosis ( ras ) is an important and frequently unrecognized contributor to refractory hypertension ( htn ) , ischemic nephropathy , and cardiac destabilization syndromes ( unstable angina , flash pulmonary edema , and decompensated heart failure).15 atherosclerotic ras is a progressive disease leading to renal atrophy over time and chronic kidney disease despite control of htn.613 presence and severity of incidental ras is an independent predictor of mortality in atherosclerotic patients regardless of the mode of treatment of underlying coronary artery disease.1315 the prevalence of ras has been reported to be in the range of 2030 percent in high risk populations including patients with known atherosclerotic vascular disease elsewhere.1618 in these patients invasive screening for ras is highly cost - effective especially when done at the time of another invasive diagnostic procedure like cardiac catheterization , and may affect treatment strategies.19 atherosclerosis is a diffuse process but affects certain regions of the vascular bed preferentially . the association between extent and severity of cad and ras has been well established in most previous studies,1214 but a few has been addressed the relationship between the distribution of lesions in coronary tree and ras.2,8,14 the main purpose of our study was to find out if any association exists . in parallel , we evaluated the relationship between demographic variables , atherosclerotic risk factors , renal function , and levels of intra - arterial pressures during catheterization and ras . in conclusion , we postulated that these findings might help decide in which group of patients screening renal angiography could be justified following coronary angiography . over a period of 12 months from november 2008 , data collected prospectively on 500 consecutive patients who underwent simultaneous renal angiography following coronary angiography in shaheed rajaie cardiovascular medical , and research center . the indications for coronary and renal angiography were at the discretion of the attending cardiologist . demographic variables , laboratory data , and history of atherosclerotic risk factors obtained from the patients medical record . patients considered hypertensive , if they had a positive history of htn who were under life style modification and/or medical treatment . patients considered diabetic ( dm ) as either currently taking anti - diabetic medications or having more than one fasting plasma glucose ( fpg ) 126 mg / dl on laboratory record . dyslipidemia ( dlp ) defined if the patient was under medical treatment for known dyslipidemia or any of the following laboratory criteria existed : fasting low - density lipoprotein cholesterol ( ldlc ) 130 mg / dl , high - density lipoprotein cholesterol ( hdlc ) 40 mg / dl in men and 50 mg / dl in women or triglycerides 150 mg / dl . patients considered having a history of smoking if they were current or former smokers . a positive family history ( fh ) established based on a known history of cad in a first degree relative male or female less than 45 and 55 years respectively . glomerular filtration rate ( gfr ) estimated by the four variable modification of diet in renal disease ( mdrd ) equation using plasma creatinine concentration , age , and gender . according to the catheterization laboratory routine practice , all of these patients underwent abdominal aortography following coronary angiography using a pigtail catheter and 1020 degrees straight left anterior oblique ( lao ) projection with a pump injector at a rate of 15 ml / sec . in those patients for whom it was difficult to evaluate the degree of stenosis via aortography , selective renal angiography also performed using a right judkins catheter and 020 degrees straight lao projections with hand injection . by average , about 3040 ml additional contrast media were utilized which was either ultravist-300 ( shering ag , germany ) or visipaque-320 ( ge healthcare , ireland ) . coronary disease considered ostio - proximal if it observed before first diagonal or septal branch in lad artery , before first sizable obtuse marginal ( om ) branch in lcx artery and before the first bend of the vessel in rca . all angiograms digitally recorded at 15 frames / sec speed and interpreted at a consensus of two interventional cardiology fellowships . all collected data entered into a database and subsequently analyzed using spss software version 15.0 for windows ( spss ) . the relationship between ras and other variables was examined using student s t - test for normal continuous variables and chi - square test for categorical factors . continuous variables that revealed significant relationship with ras in univariate analysis categorized according to their distributions and entered into the multivariate model . numerical variables expressed as mean standard deviation ( sd ) and categorical factors as percentages . finally , independent predictors of ras derived by multivariate stepwise logistic regression analysis and expressed as odds ratios ( or ) with 95% confidence interval ( ci ) . in these cohort of patients , 264 ( 52.8% ) were male with mean age of 59.6 10.1 years and 236 ( 47.2% ) were female with mean age of 60.8 8.7 years . as for major atherosclerotic risk factors , 373 patients ( 74.6% ) had htn , 219 patients ( 43.8% ) were diabetics , 445 individuals ( 89% ) had dlp , 108 ( 21.6% ) of them were smoker and 37 subjects ( 7.4% ) had a positive fh ( table 1 ) . it was unilateral in 46 patients ( 9.2% ) and bilateral in 24 ( 4.8% ) . in 26 ( 56% ) of patients with unilateral disease , ras was detected on left renal artery and in 20 patients ( 44% ) right renal artery was involved . high - grades stenosis ( 70% luminal narrowing ) was present in 45 ( 9% ) of them [ 37 ( 7.4% ) unilateral , 81 ( 1.6% ) bilateral , 18 ( 49% ) on the left side and 19 ( 51% ) on the right ] ( fig . patients with high - grade stenosis underwent renal artery stenting at the same setting or differed intervention for another session . patients with moderate ( 50%70% ) stenosis referred to nephrologists for further assessment about intervention or medical therapy . in 346 individuals , significant cad was present ( 69.2% ) . significant ras was more common ( 18.4% , p < 0.001 ) in this group . in the remaining 154 patients ( 30.8% ) with either normal coronaries or insignificant cad , six subjects ( 1.2% ) had significant ras in which all were high - grade stenosis ( bilateral in one ) . significant ras was more common in patients with three vessel cad compared to those with single or two vessel cad . relationships between involved locations of coronary arteries and ras were significant except for lm disease ( see table 2 ) . borderline relationships observed between significant ras , serum creatinine , and egfr levels ( table 1 ) . because almost all patients were receiving statins , which has modest effect on hdlc ( less than 10% increase in hdlc ) compared with other components of lipid profile,1 only this parameter statistically analyzed . mean intra - arterial systolic , diastolic and pulse pressures during catheterization were 172.8 30.7 vs. 161.6 29.2 mmhg for systolic bp , 85.1 14 vs. 78.8 21.5 for diastolic bp and 87.7 23.7 vs. 78.8 21.5 for pulse pressure with significant ras compared to those without demonstrating a good relationship between systolic and pulse pressures but not diastolic bp and ras . at the end , by multivariate logistic regression analysis age more than 62 years ( or 2.12 ; 95% ci 1.16 to 3.48 , p = 0.013 ) , sbp greater than 150 mmhg ( or = 3.19 ; 95% ci 1.57 to 6.46 , p = 0.001 ) , pp in excess of 60 ( or = 3.82 ; 95% ci 1.11 to 13.09 , p = 0.033 ) and rca involvement ( or = 3.76 ; 95% ci 1.89 to 7.48 , p < lad artery disease showed borderline significance ( or 2.12 ; 95% ci 0.94 to 4.79 ; p = 0.069 ) . results of the models for ras 70% were almost similar to ras 50% in both univariate and multivariate analyses . prevalence of ras with different severities and of bilateral ras in this cohort of patients undergoing coronary angiography is within the range of most other studies . our study showed no difference in patients with significant ras compared to those without with respect to major atherosclerotic risk factors except for age . dzieliska et al5 and wang et al12 were reported similar results , but considerable variability seen in many other studies . in our study , age more than 62 years was an independent predictor of ras . in a number of studies , this issue addressed with different thresholds , in which it was more than 60 years at a minimum.6,9 we also found borderline relationships between serum creatinine , egfr levels , and ras . in most studies reduced levels of egfr ( specifically less than 60 bearing in mind that not all patients with even severe ras have uncontrolled htn , renal failure or other clinical clues1,12 and the fact that well proven anti - atherothrombotic medications which block rennin - angiotensin system may act as a two edged sword in the presence of significant but clinically unsuspected bilateral ras1,3 underscores the need to step beyond traditional screening for ras . additionally hemodynamically significant ras may have several deleterious systemic effects through activating this system , which may accelerate atherogenesis and contribute to cardiovascular events.13,14 there was a good relationship between intra - arterial systolic and pulse pressures and ras , which is in agreement with study of weber - mzell et al8 and rihal et al.18 in our study , systolic bp above 150-mmhg and pulse pressure in excess of 60 mmhg found to be independent predictors of significant ras . wide pulse pressure may simply reflect more advanced arteriosclerosis and renal disease and in a recent published study of dieter et al,20 pulse pressure > 100 mmhg was shown a powerful predictor of poor outcome following renal angioplasty and stenting . we found highly significant relationships between atherosclerotic involvement of lad , lcx , and rca and ras , which remained significant in their ostio - proximal segments ; this was not true for significant lm disease . as for number of coronaries involved , patients with three vessels cad showed strong relationship with ras and those with normal coronaries or insignificant cad had a potent negative association with ras . interestingly in multivariate model , three vessels cad no longer seen as an independent predictor of ras while rca involvement was a strong independent predictor of ras and lad artery disease showed borderline relationship . as far as we know this independent relationship between atherosclerotic disease of rca and significant ras not been reported before . the predilections of certain sites in vascular system to develop atheroma are clear.1 atherosclerotic ras predominantly affects the aorto - ostial segment,1 but relationship between distribution of coronary artery lesions and segments involved has not been addressed extensively . in a study by weber - mzell et al,8 lad , lcx , and rca stenosis were more frequent in patients with significant ras but in multivariate analysis , having > 2 significant coronary lesions recognized as an independent predictor of ras . in another study by conlon et al,14 lad disease there was no relationship between anatomical distribution of coronary artery lesions ( proximal , mid or distal portions ) and ras in a study by danesh et al,2 but two and 3-vessel coronary disease reported as an independent predictor of significant ras . although the therapeutic implications of incidentally detected ras has been remained controversial until now21 it may be valuable to be aware of this condition given the progressive nature of the disease , the precautions in prescribing angiotensin antagonists and possibly the need to revascularization in appropriately selected cases . given the considerable drawbacks of noninvasive imaging techniques1,2,13 and safety of renal angiography13,16,17 recognizing potential candidates for screening of ras based on readily available variables at the time of cardiac catheterization is important from a practical point of view . patients with incidental ras may deserve aggressive medical treatment and more close follow - up . simultaneous renal angiography at the time of coronary angiography might be justified in patients older than 62 years , with increased intra - arterial systolic pressure ( 150 mmhg ) and pulse pressure ( 60 ) and rca disease in the absence of traditional clinical clues .

aims : we evaluated the relationship between distribution of lesions in coronary tree and atherosclerotic renal artery stenosis ( ras).methods and results : data collected prospectively on 500 consecutive patients who underwent simultaneous renal angiography following coronary angiography . overall prevalence of ras was 26.2% ( 131 patients ) . significant ( 50% luminal diameter stenosis ) ras was present in 70 patients ( 14% ) . in 346 individuals of the study population , significant cad was present ( 69.2% ) . significant ras was more common ( 18.4% ) in this group . older age , higher intra - arterial systolic blood pressure ( sbp ) and pulse pressure ( pp ) at the time of catheterization , and 3-vessel coronary artery disease ( cad ) were associated with significant ras in univariate analysis . relationship between involved locations of coronary arteries [ left anterior descending ( lad ) , left circumflex ( lcx ) , right coronary artery ( rca ) , and their ostio - proximal portions ] and ras were significant except for left main ( lm ) disease . in multivariate model , age more than 62 years , sbp greater than 150 mmhg , pp in excess of 60 mmhg and rca involvement were independent predictors of significant ras.conclusion:simultaneous renal angiography following coronary angiography might be justified in patients with significant rca disease who are older with increased levels of intra - arterial sbp and pp .

it is an autosomal dominant disease characterized by angiodysplastic lesions ( telangiectases and arteriovenous malformations ) that affect many organs , including the skin , lungs , gastrointestinal tract , and brain.1 the genes involved in hht have been identified as endoglin ( hht type 1 ) on chromosome 9q3334 , and activin receptor ( hht type 2 ) on chromosome 12q13 . both genes are involved with the regulation of transforming growth factor ( tgf ) beta signaling pathway and expression , mainly aimed to endothelial and vascular smooth muscle cells . endoglin and alk1 knockout mice die between embryonic days 911 due to vascular defects , demonstrating the importance of these proteins in angiogenesis.1,2 this disorder is clinically characterized by cutaneous and muco - cutaneous telangiectases , severe and recurrent epistaxis and gastrointestinal hemorrhage caused by teleangiectases of the nose and upper gastrointestinal tract . patients also have arteriovenous shunts , most commonly found in the lungs , brain , and liver . pertinent findings on physical examination in patients with liver involvement vary with the extent of the disease . patients with small hepatic avms may have a normal examination while those with diffuse involvement may have hepatomegaly . the most common laboratory findings are elevated alkaline phosphatase and bilirubin levels with normal hepatocellular enzymes with cholestasis . angiographic findings include large , tortuous hepatic arteries , and dense , enlarged hepatic veins . the heart failure syndrome in owr patients is characterized by an elevated resting cardiac index beyond the normal range of 2.54.0 l / min / m2 . the assumption is that ineffective blood volume and pressure , chronic activation of the sympathetic nervous system and the rennin angiotensin / aldosterone axis with increased serum vasopressin concentration cause chronic volume overload that gradually develops ventricular enlargement , remodeling and heart failure . the definition of high output heart failure is defined by symptoms of heart failure - like dyspnea at rest or with varying degrees of exertion , orthopnea , paroxysmal nocturnal dyspnea , and pulmonary / peripheral edema ) in the presence of normal cardiac index . the prolonged increase in blood volume , the continuous increased right atrial pressure , the high pulmonary artery pressure may cause an increased left ventricular end diastolic pressure with gradual myocardial de - compensation.3,4 medical therapy involves salt restriction , diuretics , antihypertensive agents , anti - arrhythmic agents , and digoxin as clinically indicated . the particular clinical manifestation of liver involvement in patients with hereditary hemorrhagic telangiectasia may depend on the predominant type and size of shunt as well as on the effects of an abnormal hepatic blood supply . the majority of patients with liver arteriovenous malformation / shunt have a hyperdynamic circulation resulting from arteriovenous shunting , portovenous shunting , or both . practically all patients with high - output cardiac failure have shunts from the hepatic artery to the hepatic veins . other factors related to diastolic dysfunction such as older age , hypertension , and coronary artery disease may play a part in precipitating heart failure . notably , as we found and as others reported the clinical manifestations of liver involvement overlap and may fluctuate over time , with spontaneous exacerbations and remissions . it may depend on changes in shunting patterns or on the presence of reversible conditions ( e.g. anemia or atrial fibrillation ) . in some cases , pregnancy , which causes a hyperdynamic circulatory state , a woman with owr disease was admitted with high output heart failure that was demonstrated by echocardiography as a diastolic dysfunction with a restrictive pattern . we would like to suggest that high output heart failure could be presented as a diastolic dysfunction and the management could be conservative .

owr is a genetic disease , transmitted as an autosomal dominant disorder characterized by arteriovenous malformations predominantly involving the mucocutaneous epithelium . one of the significant complications is the development of arteriovenous fistulas in different organs like the liver and brain . one of the rarest complications of this arteriovenous conduit is a high - output heart failure . we would like to describe a 66 years old woman who was admitted with a high - output cardiac failure who deteriorated clinically and was treated successfully by conservative management .

in 1995 , 2,895 chinese adults ( 1,412 men and 1,483 women , aged 2574 years ) were recruited from the general population in hong kong through random telephone numbers . from 20002004 , 1,944 of them participated in the follow - up study , the hong kong cardiovascular risk factor prevalence study-2 ( crisps2 ) ( 2,3 ) . the study protocol was approved by the university of hong kong faculty of medicine ethics committee . details of the protocol have been previously reported ( 2,3 ) . in this study , raised blood pressure included both high - normal blood pressure and hypertension ( 4 ) . dysglycemia , which includes impaired fasting glucose , impaired glucose tolerance , and diabetes , was diagnosed with a 75-g oral glucose tolerance test ( 5 ) . we analyzed both the 5.6 and 6.1 mmol / l ( 100 and 110 mg / dl , respectively ) cut points for fasting glucose ( 5,6 ) . data analysis was performed using spss 15.0 for windows ( spss , chicago , il ) . a cox proportional hazards model was used to identify independent factors predicting the development of diabetes , hypertension , or both . age , sex , smoking status , alcohol use , and exercise habits were entered into the model . of the 1,944 subjects studied from 2000 to 2004 , oral glucose tolerance test results or diagnosis of diabetes were available for 1,862 subjects . flow of subjects and baseline characteristics of these men and women with different degrees of dysglycemia and hypertension are shown in an online appendix ( available at http://dx.doi.org/10.2337/dc08-0405 ) . dysglycemia and raised blood pressure were both related to age , waist circumference , waist - to - hip ratio , systolic and diastolic blood pressure , fasting and 2-h blood glucose , homeostasis model assessment estimate of insulin resistance , hdl cholesterol , and triglycerides . men and women with pre - diabetes already had obesity , blood pressure , and lipid abnormalities resembling those in diabetes . among the 1,862 subjects , 5.0% had diabetes only , 12.5% had hypertension only , and 3.9% had both conditions ; 15.3% had dysglycemia only , 13.9% had raised blood pressure only , and 13.9% had both dysglycemia and raised blood pressure . of the people with diabetes , 58% had raised blood pressure . of people with hypertension , 58% had dysglycemia , 23.7% had diabetes , and 32.2% had pre - diabetes . table 1 shows the characteristics of the 1,496 analyzable subjects who had neither diabetes nor hypertension at baseline . during a median follow - up interval of 6.4 years , 67 , 194 , and 34 subjects developed diabetes only , hypertension only , or both , respectively . diabetes and hypertension shared similar predictive factors . age , male sex , bmi , waist circumference , waist - to - hip ratio , systolic blood pressure , fasting and 2-h blood glucose , and triglycerides were related to the development of diabetes , hypertension , or both . pre - diabetes ( 5 ) was associated with a hazard ratio ( hr ) of 13.2 ( 95% ci 7.523.5 ) for new - onset diabetes . a 1-cm increase in waist circumference increases the likelihood of new - onset hypertension by 4.2% ( 0.97.7 ) . in multivariate analysis , bmi ( hr 1.11 [ 95% ci 1.031.19 ] ; p = 0.005 ) and 2-h glucose ( 2.61 [ 2.123.22 ] ; p < age ( 1.05 [ 1.041.07 ] ; p < 0.001 ) , systolic blood pressure ( 1.07 [ 1.051.08 ] ; p < 0.001 ) , and 2-h glucose ( 1.16 [ 1.041.30 ] ; p = 0.008 ) were independent predictors of new - onset hypertension . the independent predictors of the development of diabetes and hypertension together were bmi ( 1.17 [ 1.051.30 ] ; p = 0.005 ) , systolic blood pressure ( 1.05 [ 1.011.09 ] ; p = 0.011 ) , and 2-h glucose ( 1.83 [ 1.392.40 ] ; p < 0.001 ) . systolic blood pressure ( standardized discriminant coefficient 0.63 ) , 2-h glucose ( 0.51 ) , fasting glucose ( 0.43 ) , family history of hypertension ( 0.32 ) , age ( 0.29 ) , and homeostasis model assessment estimate of insulin resistance ( 0.22 ) distinguished between those who developed hypertension only from those who developed diabetes only . the overlap between diabetes and hypertension is substantial , but that between dysglycemia and raised blood pressure is even greater . over one - half of people with diabetes have raised blood pressure , and over one - half of people with hypertension have dysglycemia . the overlap between diabetes and hypertension is not accidental ; both are components of the metabolic syndrome ( 7 ) . in cross - sectional analysis furthermore , these factors predict prospectively the development of diabetes and hypertension . are there factors that distinguish between the development of hypertension and diabetes ? our analysis suggested that high baseline blood pressure , family history of hypertension , and advanced age favored new - onset hypertension , whereas elevated 2-h glucose , elevated fasting glucose , and insulin resistance favored new - onset diabetes . in conclusion , the majority of people with diabetes have raised blood pressure , and the majority of people with hypertension have dysglycemia . patients with either condition need to be screened and managed for the precursor of the other condition .

objective to investigate the association between raised blood pressure and dysglycemia.research design and methods we studied the association between raised blood pressure and dysglycemia in 1,862 subjects in the hong kong cardiovascular risk factor prevalence study cohort . we determined the factors predicting the development of diabetes and hypertension in 1,496 subjects who did not have either condition at baseline.resultsdiabetes and hypertension were both related to age , obesity indexes , blood pressure , glucose , hdl cholesterol , and triglycerides . of subjects with diabetes , 58% had raised blood pressure . of subjects with hypertension , 56% had dysglycemia . bmi and blood glucose 2 h after a 75-g oral glucose load were independent predictors of new - onset diabetes . age , systolic blood pressure , and 2-h glucose were independent predictors of new - onset hypertension . bmi , systolic blood pressure , and 2-h glucose were independent predictors of the development of diabetes and hypertension together.conclusionsdiabetes and hypertension share common etiological factors . patients with diabetes or hypertension should be screened and managed for the precursor of the other condition .

ribonucleic acids have become fashionable lately . apart from their fundamental participation in transcription and translation , recently , non - translated regions of several mrnas have been found to be capable of regulating their own expression by binding specific metabolites with high affinity in complete absence of proteins [ ( 1 ) , reviewed in ( 2 ) ] . these regulatory elements , termed riboswitches , appear to be highly conserved , the extreme case being that of the thiamine pyrophosphate ( tpp ) riboswitch , which has been found in all three kingdoms of life ( 3 ) . riboswitches comprise two parts , a sensing element or aptamer , which forms a complex structure capable of binding the metabolite , and an effector element , or expression platform capable of transforming the signal into a biological response . the aptamer is the most conserved , having been selected to bind an unchanging molecule such as a vitamin or an amino acid . upon binding , a shift between two mutually exclusive rna secondary structures in the effector element occurs . these pairs of structures of the expression platform can represent a transcriptional terminator / anti - terminator , a shine - dalgarno sequester / anti - sequester or even an active / inactive ribozyme ( 2,4 ) . it is not uncommon for different organisms to use the same sensing element , yet different effector elements . although the usual method to define a riboswitch involves locating a conserved secondary structure in the rna molecule , the highly restricted nature of the sensing element argues that sequence alone should be enough to locate riboswitches correctly . we have previously developed a computer algorithm capable of finding bacterial regulatory motifs , based exclusively on sequence conservation in the regulatory regions of orthologous groups of genes ( 5 ) . the main restrictions of our method are that a regulatory element must be closely associated with at least one cog ( cluster of orthologous groups of proteins ) ( 6 ) and it must be present in at least five non - redundant genomes . on the other hand , the advantage is that it is an automatic process , requiring no previous regulatory information to produce relevant results , and as such , can be easily run every time that new genomes or annotations are available . we updated our previous results ( 5 ) , taking into account 223 complete genomes . from these , a reduced set of 145 non - redundant organisms was obtained using cvtree ( 7 ) . additionally , our results included many regulatory elements that are also known to depend on structured rna for recognition , such as the gram - positive t - box and the pyrr protein binding site . we thus call our set of regulatory elements : riboswitch - like elements ( rles ) , given the fact that almost all the identified conserved signals were rna - dependant regulatory elements . ribex is a web server that allows any user to easily find any rle in the sequence of his / her interest . since most known riboswitches are associated with attenuators , we have included the option of searching for transcriptional and translational attenuators , which can help in selecting the most likely candidates , as has been shown by barrick et al . additionally , our web server displays representative drawings of the open reading frames ( orfs ) and their corresponding regulatory elements , any of which can be selected , in order to acquire its sequence for submission to ncbi 's blast server ( 8) . every rle is linked to a list of genes that are predicted to be subject to its regulation . the genome context of these genes , analyzed with our local gecont web server ( 9 ) , in addition to the scores of the pre - computed rles , can be of great assistance when evaluating the likelihood of a new prediction . a great resource when working with rna families is the rfam database ( 10 ) . , rfam contains a total of 503 families , 125 of them are non - coding , and 11 of these are annotated as riboswitches . we were able to recover automatically all but one of these riboswitches , missing the ykok element . our matrices for the most abundant riboswitches perform very well when compared with the co - variance models used by rfam ( 90% coverage when analyzing bacterial sequences ) . less common riboswitches ( e.g. lysine and purine ) are more difficult to model with sequence - based weight - matrices . our data set also contains six more rles that coincide with an rfam cis - regulating member and 341 rles that do not have a match and thus remain as predicted elements . we have calculated a p - value , assuming a hyper - geometrical distribution , for each rle to be over - represented in a given cog or kegg pathway ( 11 ) . as far as we know there are only two servers , beside ours , that can be used to locate riboswitches in a given sequence : riboswitch finder ( 12 ) which , in its current implementation , only searches for the purine - sensing riboswitch , and rfam , that has an option to locate riboswitches in any sequence , but as co - variance searches have high computational requirements , the sequence length is limited to 2 kb . ribex , in addition to performing searches on larger sequences , allows the user a greater view of the regulatory potential of his sequence , by showing the orfs and predicted attenuators . the 341 predicted rles also make ribex a great complement to the curated families contained in rfam . the server is divided into modules , which are written in , and tied together with perl . the program takes the sequence provided and splits it into overlapping windows of 500 nt . each of these smaller sequences are searched for the selected rles with mast ( 13 ) , using matrices obtained as detailed in our previous work ( 5 ) . our method defines each rle as several non - overlapping motifs , so we restrict the search to 500 nt to avoid false positives where the individual motifs are too far apart . when an rle passes the selected e - value cutoff , the positions , size of each motif and final score of the regulatory element are recorded . the default options are for a resulting protein of at least 80 amino acids beginning with a start codon ( atg , gtg or ttg ) and ending with a stop codon ( taa , tag or tga ) . by default , these are predicted according to an algorithm developed in our group and described elsewhere ( 14 ) . the predicted secondary structure of each attenuator and its free energy is recorded . upon clicking on the image of the attenuator , an additional window will be opened showing this information . to avoid false positives , the web page is generated on the fly by a perl script that controls all the other modules . the images are generated using the gd graphics library , and the interactivity between windows and frames is provided with javascript . figure 1 shows a typical ribex output . the input sequence was a region of 4000 immediately upstream from one of the orfs ( drawn as blue arrows ) the three motifs that comprise the tpp riboswitch ( red boxes ) can be seen , as well as a transcriptional attenuator ( black lollipop ) . a separate window acts as a figure legend indicating the score for each regulatory element found ( in this case , only the tpp riboswitch ) . a typical scenario might include clicking on the second orf , and sending the sequence to the blast web server , showing it to be identical to several thic proteins . clicking on the tpp riboswitch motif in the figure legend box opens a window with the genes that are predicted to be regulated by this riboswitch , where the user can see how the motifs are distributed in different genomes . taken together , and strengthened by the presence of a transcriptional attenuator , the user would have no trouble at all concluding that his sequence contains a bona fide riboswitch .

we present ribex ( riboswitch explorer ) , a web server capable of searching any sequence for known riboswitches as well as other predicted , but highly conserved , bacterial regulatory elements . it allows the visual inspection of the identified motifs in relation to attenuators and open reading frames ( orfs ) . any of the orf 's or regulatory elements ' sequence can be obtained with a click and submitted to ncbi 's blast . alternatively , the genome context of all other genes regulated by the same element can be explored with our genome context tool ( gecont ) . ribex is available at .

bowel problems , such as constipation and distension , occur in 27%62% of patients with spinal cord injuries . acute abdominal pathology might be difficult to diagnose in a spinal cord injury patient due to its indolent course . cecal volvulus is axial twisting that involves the cecum , terminal ileum , and ascending colon . cecal bascule is a rare type of this condition associated with upward and anterior folding of the cecum ( fig . bascule , originally in french , means seesaw or counterbalanced bridge. cecal bascule is an extremely rare and accounts for less than 0.1% of causes of large bowel obstruction , . it is important to make the diagnosis without delay since it can lead to severe complications like colonic perforation or gangrenous necrosis . the importance of promptly identifying this rare diagnosis and providing the appropriate management will be discussed . 59-year - old male presented after a motorcycle crash with the following injuries : traumatic brain injury , c6c7 fracture , c5c6 spinal cord contusion , and t6 fracture . the patient remained bedridden on the ventilator . on the fifth hospital day , abdominal distention led to an abdominal radiograph , which showed marked distension of the cecum ( fig . a subsequent computed tomography ( ct ) scan showed an anteromedially displaced cecum with 8.2 cm dilation ( fig . after the patient had facial fracture repair as well as cervical and thoracic spine fixation , he tolerated a diet and was discharged 31 days after his injury . on one - month follow - up , he sustained an unstable c7 vertebral fracture with a cord contusion and quadriplegia . on the second hospital day , he had his cervical spine fixation . after two weeks of treating presumed ogilvie syndrome , the patient was taken for a laparotomy . the patient was treated with a cecostomy tube using a malecot drain through the appendiceal orifice and a cecopexy was performed . he returned to the hospital once due to cecostomy tube dislodgement and colonic distension , which was treated with endoscopic and radiologic replacement of the cecostomy tube and decompression through the cecostomy tube . on fifteen - month follow - up , 63-year - old male with morbid obesity ( bmi = 52 ) was transferred from an outlying facility after a fall . he had multi - degenerative changes to the thoracic and lumbar spine but had no acute injuries . mri showed diffuse moderate to severe degenerative narrowing of the central spinal canal and the neural foramina . on the ninth hospital day , a ct myelogram showed extensive pneumoperitoneum with cecal bascule ( fig . he had no abdominal complaints and abdominal exam was not significant likely due to masking by severe obesity and spinal cord injury . his postoperative course was complicated by a wound infection but he tolerated a diet well and was discharged on the twenty - seventh postoperative day . on two - month follow - up , 59-year - old male presented after a motorcycle crash with the following injuries : traumatic brain injury , c6c7 fracture , c5c6 spinal cord contusion , and t6 fracture . the patient remained bedridden on the ventilator . on the fifth hospital day , abdominal distention led to an abdominal radiograph , which showed marked distension of the cecum ( fig . a subsequent computed tomography ( ct ) scan showed an anteromedially displaced cecum with 8.2 cm dilation ( fig . after the patient had facial fracture repair as well as cervical and thoracic spine fixation , he tolerated a diet and was discharged 31 days after his injury . on one - month follow - up , he sustained an unstable c7 vertebral fracture with a cord contusion and quadriplegia . on the second hospital day , he had his cervical spine fixation . after two weeks of treating presumed ogilvie syndrome , the patient was taken for a laparotomy . the patient was treated with a cecostomy tube using a malecot drain through the appendiceal orifice and a cecopexy was performed . he returned to the hospital once due to cecostomy tube dislodgement and colonic distension , which was treated with endoscopic and radiologic replacement of the cecostomy tube and decompression through the cecostomy tube . on fifteen - month follow - up , 63-year - old male with morbid obesity ( bmi = 52 ) was transferred from an outlying facility after a fall . he had multi - degenerative changes to the thoracic and lumbar spine but had no acute injuries . mri showed diffuse moderate to severe degenerative narrowing of the central spinal canal and the neural foramina . on the ninth hospital day , a ct myelogram showed extensive pneumoperitoneum with cecal bascule ( fig . he had no abdominal complaints and abdominal exam was not significant likely due to masking by severe obesity and spinal cord injury . his postoperative course was complicated by a wound infection but he tolerated a diet well and was discharged on the twenty - seventh postoperative day . on two - month follow - up , the patient was in a stable condition . cecal bascule typically occurs in patients with a congenital failure of the fusion of the right colon mesentery to retroperitoneal structures that leads to increased cecal mobility . mobile cecum syndrome presents with chronic intermittent abdominal pain with spontaneous resolution after passage of flatus and is considered as a risk factor for cecal bascule or volvulus . the first patient most likely had this condition considering his pre - existing history of intermittent constipation and bloating with spontaneous resolution after passage of flatus . other risk factors for cecal volvulus include previous abdominal surgery , high fiber intake , chronic constipation and distal obstruction . cecal bascule is less likely to strangulate as the mesentery is not frequently twisted compared to volvulus . however , it can still progress to necrosis or perforation which can be life - threatening . we suggest the possibility of spinal cord injury being a risk factor for cecal bascule and volvulus . however , it might be related to increased incidence of ogilvie syndrome and bowel distension after spinal cord injury . it is considered that trauma , spinal anesthesia , or pharmacologic agents cause an impairment of the autonomic nervous system and interruption of the visceral parasympathetic fibers leaves an atonic distal colon and a functional proximal obstruction . nwanguma reported a case of a trauma patient who presented with ogilvie s syndrome that evolved into a cecal bascule while being treated with neostigmine . an abdominal radiograph is frequently obtained as the initial diagnostic imaging study for cecal bascule since most patients present with abdominal distension . ct scan confirms the diagnosis of cecal bascule in 90% of patients showing upward folding of the cecum without torsion , . ct scan is a very valuable diagnostic tool as it not only distinguishes from other types of cecal volvulus , it also helps to analyze the complications such as circumferential wall thickening , pneumatosis intestinalis , increased density in the mesenteric fat , or pneumoperitoneum . multidetector ct with three - dimensional reconstruction also allows precise diagnosis by providing accurate assessment of the volvulus . there is a 20%25% risk of cecal necrosis and the failure rate of nonoperative management approaches 95% , . colonoscopic treatment is rarely ( 5% ) successful for cecal bascule and operative treatment is commonly necessary . there are three surgical treatment options : cecopexy , cecostomy tube , and ileocecectomy or right hemicolectomy . the recurrence rates vary from zero to 28% and the mortality ranges from zero to 14% . recurrence rate after right hemicolectomy is almost nonexistent and the mortality rate after resection is reported to be 5%18% . the patient had a traumatic brain injury and was bedridden with poor nutritional status . since the patient needed to have hardware inserted for spinal stabilization , cecopexy was chosen . this decision was based on the concern for the risk of abdominal infection due to spillage or anastomotic failure . for the second patient , a cecostomy tube was placed with a cecopexy because the entire colon was severely dilated due to concomitant ogilvie syndrome and it was difficult to make a primary anastomosis . since the patient was unstable for colectomy at that time , a cecostomy tube was chosen for surgical treatment . considering these minor complications , a right hemicolectomy with diverting ileostomy or an end ileostomy with a mucous fistula were other options . for the third patient , current literature recommends avoiding cecostomy since it does nothing to address the underlying cause and may result in tube leakage , infection , colocutaneous fistula , and recurrent torsion . since the outcome after resectional surgery for an acute cecal volvulus is markedly improved and the recurrence is almost nonexistent , an ileo - colectomy with primary anastomosis should be the preferred surgical treatment . cecopexy is also acceptable treatment option for a case in which the patient will be undergoing an operation with an insertion of hardware to prevent infection of hardware in the event of an anastomotic leak . cecal bascule is a rare disorder that can be complicated after trauma especially with spinal cord injury . right hemicolectomy is the preferred surgical treatment , whereas cecopexy is also an acceptable treatment option if hardware is inserted . written informed consent was obtained from the patient for publication of this case report and accompanying images . written informed consents were obtained from the patients for publication of this case series report and accompanying images . i , yuichi ishida , m.d . accept full responsibility for the work and/or the conduct of this study , had access to the data , and controlled the decision to publish .

introductioncecal bascule is a rare cause of intestinal obstruction associated with upward and anterior folding of the ascending colon . we report three patients who presented with spinal cord injury complicated with a cecal bascule . diagnosis and management of cecal bascule is discussed.presentation of casespatient 1 : 59-year - old male sustained a traumatic brain injury and cervical spinal cord injury after a motorcycle crash . he had abdominal distension and the diagnosis of cecal bascule was made . cecopexy was performed.patient 2 : 51-year - old male sustained an unstable c7 vertebral fracture with a cord contusion and quadriplegia after a diving incident . after an unsuccessful medical management of the colonic distension , the patient was taken for a laparotomy and cecal bascule was found . a cecostomy and a cecopexy were performed.patient 3 : 63-year - old male was transferred after a fall . he had diffuse degenerative changes in the thoracic and lumbar spine . he was found to have a perforated cecal bascule . he had a right hemicolectomy with an ileocolic anastomosis.discussionwe suggest the possibility of spinal cord injury being a risk factor for cecal bascule . currently , right hemicolectomy is recommended for the treatment of cecal bascule . cecopexy is also acceptable treatment option for a case in which the patient will be undergoing an operation with an insertion of hardware.conclusionthe diagnosis of cecal bascule should be considered for trauma patients with cecal distention without delay in order to prevent disastrous complications .

prophylactic antibiotics have been proven to be an effective measure for the prevention of postoperative infection . the standard practice is to administer prophylactic intravenous antibiotics only on the day of surgery in western countries [ 811 ] ; however , in japan , prophylactic intravenous antibiotics are administered for several days postoperatively , and one - day antibiotic infusion is rare . a questionnaire survey of japanese orthopaedic surgeons showed that 86% of surgeons administered intravenous antibiotics for 7 days or longer after prosthetic surgery . we have no precise guidelines on the prophylactic use of antibiotics in japanese orthopaedic surgery . at our institution , since july 2004 , antibiotics have been infused only on the day of primary total hip arthroplasty ( tha ) and total knee arthroplasty ( tka ) . here , we retrospectively compared the outcome of one - day intravenous antibiotic administration with that of long - term intravenous antibiotic administration . 223 patients who underwent arthroplasties received intravenous antibiotics only on the day of surgery ( group a ) . another 104 patients who underwent arthroplasties received intravenous antibiotics for at least 3 days after surgery ( group b ; control group ) . no significant differences were found in terms of age , body mass index ( bmi ) , sex , procedures , and operative time between the groups . the mean follow - up periods were 32 16 months in group a and 51 23 months in group b. patients who underwent revision arthroplasty and those who were susceptible to infection due to factors such as diabetes mellitus , rheumatoid arthritis , or steroid therapy , were excluded from this study . the skin of the surgical field was not shaved but was prepared with 10% povidone iodine solution twice before draping . all thas were performed by one surgeon ( a. sudo ) , and all tkas were performed by another one surgeon ( m. hasegawa ) . we performed tha with cementless prostheses ; however , we used only cemented prostheses in tka . sutures were removed 14 days after surgery . for both groups , antibiotics were intravenously infused starting 30 minutes before surgery , with the second administration approximately 6 hours later . the doses of intravenous antibiotics were 2 - 3 grams per day according to the instructions . in group a , antibiotics were intravenously infused on the day of surgery , and oral antibiotics were administered for 5 to 77 days postoperatively ( average , 18 days ) . in group b , antibiotics were intravenously infused for 3 to 24 days with an average of 8 days ( twice daily in the morning and at night ) , and oral antibiotics were administered for 3 to 72 days postoperatively with an average of 16 days . oral antibiotics were administered when the serum c - reactive protein ( crp ) level dropped below 1.0 mg / dl ( figure 1 ) . in group a , pipc ( piperacillin , -lactam antibiotics ; taisho - toyama pharmaceutical co. ltd , tokyo , japan ) was used in 97 patients , cez ( cefazolin , a first - generation cephalosporin ; otsuka pharmaceutical co. ltd . , tokyo , japan ) was used in 72 patients , sbt / abpc ( sulbactam sodium / ampicillin sodium , a combination drug of ampicillin and -lactamase inhibitor ; pfizer japan inc . , tokyo , japan ) was used in 30 patients , ctm ( cefotiam , a second - generation cephalosporin ; takeda pharmaceuticals co. ltd . , osaka , japan ) was used in 12 patients , fmox ( flomoxef , a second - generation cephalosporin ; shionogi & co. ltd . ) in 9 patients , and others were in three patients . cfpn - pi ( cefcapene pivoxil , an oral cephalosporin ; shionogi & co. ltd . , osaka , japan ) was then administered orally . in group b , cez was used in 38 patients , pipc in 28 patients , abst / sbt in 10 patients , fmox in 10 patients , ctm in 9 patients , and others in 9 patients were intravenously infused , followed by oral administration of cfpn - pi . we evaluated the presence of wound infection from signs such as persistent fever , localized fever , localized redness , or purulent discharge and nonwound infection , such as respiratory or urinary tract infection . we monitored liver and renal functions as well as inflammatory markers including serum crp and white blood cell count ( wbc ) . the study was conducted according to the ethical principles stated in the declaration of helsinki and local regulations . we compared the patients ' baseline characteristics using the mann - whitney u test and chi - squared test . the analysis was performed using the statview statistical software package ( version 5.0 ; sas institute , cary , nc , usa ) . none of these patients developed wound infection or nonwound infection during the followup for a minimum 12 months after surgery . we found liver function test abnormalities in 67 of the 223 patients ( 30% ) in group a and 26 of the 103 patients ( 25% ) in group b. there is no significant difference between group a and b ( p > .05 ) . in group a , 8 patients had 2-fold and 4 patients had more than 3-fold elevation of aspartate aminotransferase ( ast ) . 15 patients showed 2-fold and 11 patients had more than 3-fold elevation of alanine aminotransferase ( alt ) . in group b , 4 patients had 2-fold and 3 patients had more than 3-fold elevation of ast . the mean crp level was elevated to 9.7 mg / dl for group a and 8.1 mg / dl for group b , but at 7 days after surgery , it had dropped markedly to 2.9 mg / dl for group a and 2.8 mg / dl for group b and did not increase again ( figure 2).for both groups , wbc was elevated the day after surgery . however , it normalized at 3 days after surgery in most patients : 6445/ml for group a and 6241/ml for group b. none of the patients exhibited persistent fever . when first- and second - generation cephalosporins were infused only on the day of surgery , the incidence of deep infection ranged from 0 to 1.6% , and no significant difference was observed between one - day and long - term preventive antibiotic therapy [ 1418 ] . a recent systemic review has shown that there is no advantage to prolonging the antibiotic prophylaxis for arthroplasty beyond 24 hours . a study in the norwegian arthroplasty register showed that the results were better if antibiotics were given 4 times on the day of surgery , as compared to once , twice , or 3 times . no further improvement was found in the patients given antibiotics infusion for 2 days or 3 days when compared to systemic prophylaxis 4 times in one day . a pronounced rise of the crp level on the third postoperative day after arthroplasty is normal , but a further rise at one to 2 weeks suggests the presence of a serious complication , including infection . if we had found an upward trend in the crp level after the third postoperative day , we would have continued the long - term intravenous administration of antibiotics . none of the patients in the present study developed postoperative infection ; hence , one - day infusion of antibiotics on the day of surgery appears to be effective in preventing infection . problems with long - term intravenous antibiotic administration include the emergence of drug - resistant bacteria , drug - induced hepatopathy and nephropathy , and high medical cost [ 16 , 21 , 22 ] . in the present study , group b showed an increased incidence of liver function test abnormalities , thus suggesting an association between long - term antibiotics infusion and liver function test abnormalities . regarding medical costs , the average daily cost of intravenous cez and ctm is 2,582 japanese yen ( about $ 28.7 ) , while that of oral cfpn - pi is only 283 japanese yen ( about $ 3.1 ) . because the average length of infusion for group b was 8 days , the difference in cost between groups a and b was 16,083 japanese yen ( about $ 179 ) . by intravenously administering antibiotics only on the day of surgery , it is possible to lower medical costs , and this is beneficial in terms of hospital management from the viewpoint of comprehensive medicine . the limitations of this study include its small sample size and the effect of the oral administration of antibiotics . in addition , many kinds of intravenous antibiotics were used , so the number of patients in each antibiotics group was small to perform detail statistical analyses . because drug - resistant bacteria increase in association with the quantity of antibiotics , and contact with antibiotics in low concentration confers a risk of acquiring resistance , the administration of oral antibiotics might not be needed as prophylaxis against surgical site infection . one - day antibiotic infusion was as effective as long - term antibiotic infusion in preventing infection after arthroplasty . long - term intravenous infusion of antibiotics was associated with a higher incidence of liver function test abnormalities . in addition , one - day intravenous infusion of antibiotics on the day of surgery achieved greater cost effectiveness .

intravenous antibiotics effectively reduce the prevalence of postoperative infection . however , japanese orthopaedic surgeons have no consensus with regard to the optimal duration of prophylaxis . the aim of this study is to compare the outcome of one - day intravenous antibiotic administration with that of long - term intravenous antibiotic administration . patients who underwent total hip or knee arthroplasty were divided into 2 groups to receive one of 2 prophylactic protocols retrospectively . group a ( 223 patients ) received intravenous antibiotics twice only on the day of surgery , whereas group b ( 104 patients ) received intravenous antibiotics for at least 3 days after surgery . we analyzed the wound infection rate and monitored liver and renal functions . none of these patients had a postoperative infection . no liver dysfunction and renal dysfunction were observed . one - day antibiotic infusion was as effective as long - term antibiotics in preventing infection after arthroplasty and achieved greater cost effectiveness .

. potential complications of anterior hip dislocations are a neurovascular injury to femoral vessels or acetabular fractures . we report a rare late complication of morel - lavallee syndrome occurring 3 weeks after an anterior dislocation of the hip in a 43-year - old male . the authors recommend surgeons to have a high index of suspicion for this syndrome and a stringent follow - up examination of the patient . they are relatively rare and constitute 10 - 15% of all dislocations [ 1 , 2 ] . the strong anterior capsule and ligament of bigelow anterior dislocations usually lead to fractures of the anterior acetabular wall or femoral head fractures or neurovascular injuries of the femoral vessels . we report a rare case of morel - lavallee lesion complicating an anterior dislocation of the hip . a 43-year - old presented to the emergency department following a history of road traffic accident . he was apparently standing on the road when a four - wheeler hit him from behind . the patient felt a snap following which he was unable to stand up on his affected limb . the patient was laid down in a supine position ; the pelvis was fixed by an orthopedic surgeon while another orthopedic surgeon performed a continuous axial extension of the right leg till the femoral head was located distal the acetabulum , which was checked by fluoroscopy . at that moment , the hip was flexed and internal rotated . the patient presented to us after 3 weeks with severe pain over the anteromedial aspect of thigh . there was a tense cystic swelling with ecchymosis over the medial side of thigh ( fig . aspiration using an 18 gauge needle yielded around 120 ml of blood mixed with clots ( fig . the patient was taught pelvic bridging exercises to avoid bed sores , isometric adductor , and gluteal , and hamstring strengthening exercises initially . he was then made to perform quadriceps strengthening and range of movement exercises of the knee joint . after 4 weeks , at the end of 6 weeks , the patient was made to weight bear . ( a and b ) ultrasound photograph showing 60 - 70 ml collection in the thigh . almost 35% of patients who suffer from anterior dislocations are in their third decade of life [ 1 , 2 ] . on the contrary , the ratio of anterior to posterior dislocations varies from 1:10 to 1:19 [ 1 , 3 , 4 ] . the rarity of these injuries is due to the strong anterior capsule and the ligament of bigelow . anterior dislocations are of two types , the superior iliac or pubic type and the inferior obturator type . in our patient , it was of the obturator variety of anterior dislocation . the mechanism of injury in anterior dislocation of the hip is usually one of the three types . finally blow to the back , when the patient is squatting seems to be a relatively more common mode of injury [ 1 , 3 , 4 ] . we suspect that the limb probably was forced into external rotation , abduction , and hyperextension at the hip joint at the time of impact . the sequence of events that occur following trauma are the neck of the femur or the greater trochanter impinges on the rim of the acetabulum , which in turn levers out the femoral head out of the acetabulum socket . the femoral head usually pushes itself out through a tear in the anterior capsule [ 1 , 3 ] . the incidence of avascular necrosis of the femoral head in an unreduced hip after 6 h varies from 0 to 22% [ 1 , 3 ] . aware of these statistics , a successful attempt was made to reduce the hip joint within 2 h of trauma under general anesthesia . the authors do not recommend a reduction of the hip joint under the effect of muscle relaxants , as more often than not the relaxation is not adequate to successfully reduce the joint . moreover , excessive manipulation is required which may lead to trauma of the retinacular or circumflex vessels . the usual complications after an anterior dislocation of the hip include neurovascular injury of the femoral vessels [ 1 , 5 ] , femoral head fracture [ 1 , 6 ] , and acetabulum fractures . morel - lavelle lesion refers to a cystic lesion secondary to blunt injury and especially in degloving injuries . the mechanism behind these injuries is when a tangential shearing force acts on the relatively mobile tissue , it gets torn away from the underlying firm muscle fascia . this creates a dead space between the two tissue planes which is filled with blood and/or lymph from the disrupted perforating vessels or capillaries [ 7 , 8 ] . morel - lavelle lesions are more often encountered over the trochanteric region or the proximal thigh ; however , it has been reported in other locations such as the lower lumbar region or the calf . furthermore , they have been associated with pelvicor acetabular fractures [ 7 , 9 ] . in our patient , during the course of the dislocation of the femoral head anteriorly , it induces a shearing force on the subcutaneous tissues which get dragged along with it . the key steps of the process have been identified ; after the initial formation of the potential blood filled space , there is evolution of this hematoma with absorption of the blood , which is replaced by serosanguineous fluid [ 7 , 10 ] . the last step in this chain of events is the formation of a peripheral fibrous capsule secondary to an anti - inflammatory reaction . the entrapment of fluid within the cyst may maintain a degree of chronic inflammation that could cause the gradual enlargement of the lesion over a long period . in our patient , we aspirated hematoma clots from the site of injury , i.e. , along the anteromedial aspect of thigh . the diagnosis was made clinically by palpating an extremely tender area on the anteromedial aspect of thigh . most authors , however , agree that the imaging modality of choice is magnetic resonance imaging ( mri ) . however , the findings of an mri may vary significantly , based on the chronicity and internal contents of the lesion . despite the rarity of this lesion , mri imaging has been used for the only so far available classification system [ 7 , 11 ] . the available treatment modalities depend on the timing of identification of a morel - lavelle lesion . if it is detected during the acute phase , percutaneous drainage , and compression may be sufficient . however in later stages , surgical aspiration or excision of the fibrous capsule may be warranted [ 7 , 12 , 13 ] . after surgery , it would be necessary to place suction drain to drain out any remnant fluid from the cyst . the differential diagnosis of a morel - lavelle lesion includes posttraumatic fat necrosis , coagulopathy - related hematoma , and posttraumatic early stage myositis ossificans [ 7 , 12 ] . in conclusion , we presented a rare case of a morel - lavelle lesion following anterior dislocation of the hip . although rare , this particular entity should be looked for as it may present as a late complication such as our case . the results are usually good . however , surgical excision is the preferable treatment modality when the lesion is advanced . atypical complications like morel - lavallee syndrome after hip dislocations present an unusual challenge during the treatment of the patient a diagnosis of morel - lavallee syndrome should be thought of as a potential late complication .

introduction : hip dislocations are serious injuries as hip joint is an extremely stable joint . it requires a significant amount of force to produce such an injury . anterior dislocations are uncommon . potential complications of anterior hip dislocations are a neurovascular injury to femoral vessels or acetabular fractures.case report : we report a rare late complication of morel - lavallee syndrome occurring 3 weeks after an anterior dislocation of the hip in a 43-year - old male . the patient presented to us with history.conclusion:morel-lavallee syndrome is a rare complication . however if diagnosed early can be successfully treated with minimal burden to the patient . the authors recommend surgeons to have a high index of suspicion for this syndrome and a stringent follow - up examination of the patient .

knowing the fact that both tryr and gr has exclusive substrate specificity , various molecules have been explored as inhibitors of tryr which includes hydrophobic linear polyamine derivatives and the naturally occurring bis ( tetrahydrocinnamoyl ) spermine , ponasik et al . to further address the need for new compounds and new compound classes , richardson et al . these compounds were screened against tryr and the top hits counter - screened against gr and live t. brucei parasites , yielding the ic values , selectivity for tryr over gr and antiparasitic activity . among all the 1266 compounds from sigma - aldrich lopac1280 library , several tricyclic derivatives were identified as a potent inhibitor tryr [ figure 3 ] . structures of various tricyclic drug having potent trypanothione reductase inhibiting activity and selectivity of human glutathione reductase recently , lunarine a spermidine - based macrocyclic alkaloid [ figure 4 ] has been identified as a competitive , time - dependent inhibitor of tryr . lunarine is composed of a spermidine chain with the terminal nitrogen atoms forming amide linkages with two , -unsaturated carboxylic acid functions disposed upon an unusual 3-oxohexahydrodibenzofuranyl tricyclic scaffold . structure of kukoamine a and lunarine a study done by hamilton et al . presented a possible mechanism for this time dependent inhibition , which involves the covalent modification of a redox - active cysteine residue in the active site of tryr ( c53 ) by conjugate addition to one of these unsaturated amide moieties in the lunarine macrocycle [ figure 5 ] . this was supported by both the requirement for the enzyme in its reduced form and the presence of a potential michael acceptor unit in the inhibitor . proposed mechanism for time - dependent inactivation of trypanothione reductase by the reversible formation of a covalent adduct between an active site thiol ( c53 ) and one of the , -unsaturated amide groups of lunarine the hamilton et al . further explored this approach by preparing some benzofuranyl - based acyclic bis - polyamine analogues ( 1 - 5 ) of lunarine . in their approach the acyclic bis - polyamine derivatives were chosen since bis - polyamine functionalized disulfides such as the naturally occurring n - glutathionylspermidine disulfide and the synthetic bis - dimethylaminopropyl- and bis - n - methylpiperazinyl amides of ellman 's reagent ( dtnb ) are known tryr substrates . these three polyamine chains were chosen for functionalisation of a 3 , 5-disubstituted benzofuranyl template to give potential inhibitors ( 1 - 5 ) . in their series of compounds the bis - polyaminoacrylamide derivatives ( 1 - 3 ) were shown to be competitive inhibitors , but only the bis-4-methyl - piperazin-1-yl - propylacrylamide derivative 3 displayed time - dependent activity . analysis of in vitro activity showed that these compounds were simple competitive inhibitors of tryr , with respect to t[s]2 . the starting material 4 , 5 and 6 which do not have polyamine side chain were also evaluated for enzyme inhibitory activity against tryr . it was observed that due to the absence of any polyamine side chains , neither the diester 6 nor the diacid 4 showed any inhibitory activity towards tryr at 100 m concentrations . bonnet et al . designed and synthesized a series of symmetrical substituted 1,4-bis ( 3-aminopropyl ) piperazines derivatives . the compounds were prepared by reacting 1,4-bis ( 3-aminopropyl ) piperazine with various aldehydes via reductive amination . all compounds were tested for their inhibitory potency towards tryr from t. cruzi and their trypanocidal effects upon t. cruzi trypomastigote as well as for their trypanocidal effect upon t. brucei trypomastigote stage . they also studied cytotoxicity toward human mrc-5 cells ( diploid embryonic lung cell line ) . their study revealed that in the aromatic series the most potent tr inhibition was observed for polyphenyl derivatives 7 and 8 ( ic50 of 32 and 28 m ) respectively . these two compounds showed 100% inhibition on t. brucei at a concentration of 6.3 and 3.1 m . a study done by chibale et al . reported design and synthesis of 9 , 9-dimethylxanthene derivatives ( 9 - 14 ) as potential inhibitor of tr . they designed target compounds in which 9 , 9-dimethylxanthene ring was exploited as an aromatic hydrophobic tricyclic moiety that bears resemblance to the aromatic hydrophobic tricyclic moieties found in other tricyclic compounds already reported as competitive inhibitors of tr , where the tricyclic moiety binds in the hydrophobic pocket involved in recognition of the spermidine moiety of trypanothione disulfide , the substrate for tr . moreover , in 9 , 9-dimethylxanthene system potential multiple sites are provided by chemically reactive 2 , 7 and 4 , 5 positions for introducing chemical diversity . apart from these functions , they also introduced terminal tertiary amino group ( exemplified by the dimethylamino group ) into compounds ( 9 - 14 ) to provide a positive charge which has been shown to favor tryr over gr , the closest related host enzyme . thorough analysis of results of tryr inhibitions study [ table 2 ] , it was found that compounds ( 9 - 11 ) bearing either one ( 10 ) or no methylene spacer ( 9 and 11 ) between the tricyclic moiety and the secondary nitrogen atom generally show weaker inhibition of tr compared to derivatives with two or three carbon methylene spacer ( 12 , 13 and 14 ) [ figure 6 ] . percentage inhibition of tryr and ed50 of compounds ( 9 - 14 ) potential compounds from different literature they concluded that within the series of compounds ( 9 - 15 ) , there is no clear correlation between potency as inhibitors of tr and the in vitro antiparasitic activities and that there is no apparent single structural feature controlling in vitro antiparasitic activities . in another study by chibale et al . had shown that chemical structures of agents which increase accumulation and/or reverse chloroquine ( cq ) resistance reveals the importance of a hydrophobic group and a protonatable nitrogen and incidentally these are the same chemical features known to be important for potent and selective against tr inhibitor . a wide variety of structurally diverse drugs ( including mepacrine , promazine and clomipramine ) have also been described as cq resistance reversal agents . based on this observation it was envisaged by chibale et al . that these tricyclic could be utilized as dual purpose scaffolds for the discovery and development of cq resistance reversal agents and inhibitors of tryr all the tested compounds showed weak tr inhibitory activity against t. cruzi tryr . among the all derivatives of xanthenes , compound 16 showed highest tryr inhibitory activity of ic50 of 35.7 m and intrinsic antimalarial activity of ic50 = 1.748 m . a series of sulfonamide and urea derivatives of quinacrine with varying methylene spacer lengths have been tested for inhibition of tryr and for activity in vitro against strains of the parasitic protozoa trypanosoma , leishmania and plasmodium by kelly et al . the results of the studies revealed [ table 3 ] that these derivatives were superior inhibitors of tryr relative to quinacrine with the best compound being 40 times more potent . results of their studies revealed that sulfonamide derivatives were more active than urea in inhibiting tryr and this trend of activity did not correlate with the in vitro activities against l. donovani , t. cruzi , and t. brucei . in vitro sensitivity of the parasite to quinacrine analogue ( 17 - 19 ) and ( 20 - 23 ) girault et al . designed and optimized various bis ( 2-aminodiphenylsulfides ) derivatives and tested for inhibitory activity against tryr from t. cruzi . in the series bis ( 2-aminodiphenylsulfides ) compounds possessing three side chains were synthesized and various moieties were introduced at the end of the third side chain , including acridinyl or biotinyl moieties for fluorescent labeling studies . the results of the tr inhibition screening showed that most potent inhibitor ( 24 ) with ic50 = 200 nm , whereas the tricyclic derivatives ( 25 ) exhibited ic50 of 250 nm . all the compounds were also tested in vitro upon t. cruzi and leishmania infantum amastigotes , upon t. brucei trypomastigotes . in order to provide improved tricyclic derivatives as an inhibitor of tryr , richardson et al . they prepared a derivative having additional propylbenzene ring on piperazine moiety of prochlorperazine and found 10 fold increase in ic50 against tryr ( ic50 = 0.75 m ) . the enzyme tryr from trypanosomal and leishmanial parasites meets most of the ideal features as a drug target needed for developing a potent and specific inhibitor for treating infections caused by trypanosomal and leishmanial parasites . of various class of compounds developed as an inhibitor of tryr , tricyclic derivatives have come up with potential to be further exploited as the drug candidate for the treatment of trypanosomiasis and leishmaniasis . although a lot research work has been done to provide tricyclic based derivatives as future therapeutic agents against these parasitic diseases , but yet none of tricyclic agent is able to reach at the level of approval as an effective therapy for trypanosomiasis and leishmaniasis .

trypanosomiasis and leishmaniasis are two most ruinous parasitic infectious diseases caused by trypanosoma and leishmania species . the disease affects millions of people all over the world and associated with high morbidity and mortality rates . the review discuss briefly on current treatment of these parasitic diseases and trypanothione reductase ( tryr ) as potential targets for rational drug design . the enzyme trypanothione reductase ( tryr ) has been identified as unique among these parasites and has been proposed to be an effective target against for developing new drugs . the researchers have selected this enzyme as target is due to its substrate specificity in contrast to human analogous glutathione reductase and its absence from the host cell which makes this enzyme an ideal target for drug discovery . in this review we have tried to present an overview of the different tricyclic compounds which are potent inhibitors of tryr with their inhibitory activities against the parasites are briefly discussed .

uterine granuloma is a rare entity and may be either focal or diffuse in nature . diffuse granulomas represent a local reaction without an obvious cause or may be associated with infection or systemic granulomatous disorders . infective conditions associated with uterine granulomas could be tuberculosis , atypical mycobacteria , endemic mycosis , cytomegalovirus infection and parasites . we report two cases of uterine granuloma , the first in which there was diffuse non - necrotizing granuloma . the second case showed diffuse granulomas with caseation in the myometrium and was positive for acid fast bacillus ( afb ) stain . a 50-year - old patient presented in august 2010 with heavy and irregular bleeding per vaginum for last 10 months . she had undergone dilatation and curettage ( d and c ) and cervical biopsy in december 2009 for menorrhagia . she had a second episode of menometrorrhagia in march 2010 followed by a repeat d and c. the endometrial curettings was reported as simple hyperplasia without atypia . her general , local examination and routine investigations were normal . a total abdominal hysterectomy with bilateral salpingo - oophorectomy was performed and the patient was discharged in satisfactory condition on eighth post - operative day . histology revealed endometrium in proliferative phase and myometrium showed multiple non - necrotizing epithelioid cell granulomas . photomicrograph showing non - caseating epithelioid cell granulomas with multinucleated giant cells present in the myometrium ( h and e , 200 ) a 40-year - old presented with pain and mass lower abdomen of five months duration with no menstrual irregularity . general physical examination was normal , local examination was suggestive of fibroid corresponding to size of 18 weeks pregnant uterus . ultrasonography revealed a large single intramural fibroid 10 9.7 cm with thin endometrium and normal ovaries . histopathological examination revealed endometrium in secretory phase , uterine tumor as leiomyoma and in addition myometrium showed caseating epithelioid granulomas along with langerhans and foreign body giant cells [ figure 2 ] . stain for afb was positive . patient was started on att despite hysterectomy and absence of tuberculosis elsewhere because the adnexa was left behind where the possibility of a tubercular focus could not be ruled out . a 50-year - old patient presented in august 2010 with heavy and irregular bleeding per vaginum for last 10 months . she had undergone dilatation and curettage ( d and c ) and cervical biopsy in december 2009 for menorrhagia . she had a second episode of menometrorrhagia in march 2010 followed by a repeat d and c. the endometrial curettings was reported as simple hyperplasia without atypia . her general , local examination and routine investigations were normal . a total abdominal hysterectomy with bilateral salpingo - oophorectomy was performed and the patient was discharged in satisfactory condition on eighth post - operative day . histology revealed endometrium in proliferative phase and myometrium showed multiple non - necrotizing epithelioid cell granulomas . photomicrograph showing non - caseating epithelioid cell granulomas with multinucleated giant cells present in the myometrium ( h and e , 200 ) a 40-year - old presented with pain and mass lower abdomen of five months duration with no menstrual irregularity . general physical examination was normal , local examination was suggestive of fibroid corresponding to size of 18 weeks pregnant uterus . ultrasonography revealed a large single intramural fibroid 10 9.7 cm with thin endometrium and normal ovaries . histopathological examination revealed endometrium in secretory phase , uterine tumor as leiomyoma and in addition myometrium showed caseating epithelioid granulomas along with langerhans and foreign body giant cells [ figure 2 ] . stain for afb was positive . patient was started on att despite hysterectomy and absence of tuberculosis elsewhere because the adnexa was left behind where the possibility of a tubercular focus could not be ruled out . when clinicians encounter patients with granulomatous inflammation , they are faced with a diagnostic dilemma to determine its cause . non infections conditions include granulomatous inflammation following surgical instrumentation , foreign body reaction , systemic granulomatous disorders like sarcoidosis , systemic vasculitides like giant cell arteritis or may be idiopathic i.e. , without an obvious underlying cause . the first case in our study showed diffuse granulomatous lesions in myometrium of non - necrotizing variety . there was history of surgical intervention for uterine bleeding in the form of dilatation and curettage done twice at an interval of three months . , showed that 8 of 11 patients with incidental granulomas of the uterus had a known history of instrumentation , which consisted of dilatation and curettage ( n = 4 ) , endometrial biopsy ( n = 2 ) , hysterosalpingogram ( n = 1 ) and hysteroscopy ( n = 1 ) . none of the patients had clinical evidence of sarcoidosis or systemic infection and stains for microorganisms were negative . the clinical scenario of the first case correlates with this study where well formed , non - necrotizing granulomas of the uterus were found with a history of instrumentation . the patient had endometrial defects as shown on histopathology which can explain all the clinical features . similarly there was no evidence of systemic granulomatous disease or tuberculosis based on clinical and laboratory evidence . hence a history of instrumentation may explain the presence of uterine granulomas in the first case . despite its contiguity with endometrium , sinha et al . , reported a case of myometrial tuberculosis detected on sonography as multiple anechoic areas of variable size with well defined borders scattered throughout the myometrium . after receiving antitubercular treatment patient was relieved of menorrhagia and a repeat sonogram showed a homogenous myometrium with absence of anechoic areas . the second case presented with a pelvic mass suggestive of leiomyoma , confirmed on fnac and had no menstrual complaint . there was incidental detection of tubercular granulomatous inflammation of myometrium along with leiomyoma in this case . , in a 31 year study on pathology of female genital tuberculosis reported that microscopic involvement of myometrium was observed in 20% of the cases . in the indian context , tuberculosis remains the most common cause of diffuse granulomas since two thirds of tuberculosis cases in south east asia are found here . , reviewed 5,085 biopsy specimens ( 3,510 endometrial and 1,575 cervical ) of these 28 endometrial and 2 cervical biopsy specimens were reported as granulomatous inflammation , consistent with tuberculosis . myometrial involvement was not observed in any of the endometrial biopsy specimens in which myometrium was included . this supports the infrequent involvement of myometrium in genital tuberculosis . to conclude , uterine granuloma involving myometrium is rare . there is need for awareness about instrumentation causing granuloma formation , and also to look for an additional pathology such as tubercular granuloma which may present as an incidental finding warranting therapy .

uterine granulomas confined to the myometrium are uncommon . granulomas maybe infectious , non - infectious or idiopathic in origin . they may be diffuse or focal in nature . in this report , we describe two cases of granulomas of diffuse variety involving the myometrium . the first case shows non - necrotizing granuloma probably related to previous instrumentation . the second case depicts caseating granulomas along with leiomyoma of uterus .

in 95% of cases of acute cholecystitis the cause is a gallstone blocking the cystic duct subsequently leading to inflammation of the gallbladder by chemicals or bacteria ( 1 ) . the localised peritonitis that ensues means patients characteristically present with a history of severe , sudden onset , constant or colicky pain in the right upper quadrant ( ruq ) with systemic upset such as nausea , vomiting and sweating ( 2 ) . complications of this condition include gangrenous cholecystitis , gallbladder perforation , cholecysto - enteric fistula , gallstone ileus ( 3 ) and , very rarely , cystic artery pseudoaneurysms ( cap ) , which can be associated with intra - abdominal and gastrointestinal haemorrhage ( 4 ) . a 71-year old caucasian gentleman with a background of known gallstones and hypertension presented to the emergency department with a two - day history of sudden onset , severe ruq pain associated with non - bilious vomiting . his past surgical history included an appendicectomy , bilateral inguinal herniae repair as well as a l5 laminectomy several years previously . blood tests revealed the following : haemoglobin 12.7g / dl , leucocytes 23 x 10/l , neutrophils 20.7 x 10/l , na 141mmol / l , bilirubin 36mol / l , alt 25u / l , alp 101u / l , amylase 35u / l and crp 332mg / l . an abdominal ultrasound scan ( uss ) was performed the next day and reported multiple large gallstones with significant thickening of the gallbladder wall . the patient was treated with oxygen therapy , analgesia , intravenous piperacillin / tazobactam & metronidazole and a stat dose of gentamicin after discussion with the consultant microbiologist . his condition remained stable ; however , over the course of the next 7 days , he began spiking temperatures along with persistent ruq pain and increasing leucocyte count . an abdominal uss was repeated which now demonstrated a single large calcified gallstone within a contracted gallbladder and a pulsatile mass around hartman s pouch with a large amount of free fluid around the liver . this fluid was extending into the right paracolic gutter and down to the right iliac fossa . a ct angiogram ( fig.1a & 1b ) was done to delineate this pulsatile mass which confirmed a 3 cm x 1.5 cm cystic artery pseudoaneurysm ( a ) and a large collection ( c ) extending from the gall bladder fossa , surrounding the liver and extending down to the right paracolic gutter and into the pelvic brim . there was no suspicion of gallbladder perforation or empyema from the images obtained . ct angiogram ( a = cystic artery pseudoaneurysm ; b = calcified gallstone ; c = perihepatic fluid ) 3d reconstruction of ct angiogram the next step was for embolisation of the cap . a transfemoral approach was employed and a microcoil placed successfully in the cystic artery ( fig . a right sub - hepatic drain was placed , which drained a total of 1130ml of dark inflammatory fluid , in the first 24 hours . the patient clinically improved over the next 7 days , his inflammatory markers normalised and the drain was removed when dry . our literature search struggled to find a similar case with concurrent acute inflammation without haemoperitoneum . most cases of cap are invariably associated with haemoperitoneum or haemobilia ( 5 ) , and although colour doppler can be used to diagnose cap , ct angiogram seems to yield a better diagnostic image . inflammation of the gallbladder may lead to changes in the cystic artery as a result of inflammation and fibrosis encasing the arterial wall and weakening it ; resulting in aneurysm formation . these aneurysms are likely to rupture when the tamponising effect of the surrounding inflammatory fluid tension is lost , which is why drainage of the pericholic fluid was delayed until after embolisation was done . we report here a conservative treatment after microcoil embolisation with antibiotics and percutaneous drainage of pericolic fluid . our regime of antibiotics is intravenous piperacillin / tazobactam and metronidazole with a one off dose of gentamicin . the patient was kept nil orally , accurate fluid balance maintained and we noticed rapid improvement from a septic to non - septic picture . in conclusion , our experience with this case suggests that if a cap is demonstrated , microcoil embolisation is effective in its management followed by percutaneous drainage of any pericholic fluid and intravenous antibiotics ; saving the patient an emergency surgery .

cystic artery pseudoaneurysm ( cap ) is a very rare complication of acute cholecystitis . we present the unruptured cystic artery pseudoaneurysm of an oedematous , thick - walled gallbladder in a 71-year old gentleman admitted with acute calculus cholecystitis . this was managed by radiological microcoil embolisation , percutaneous drainage of pericholic fluid and conservative treatment with antibiotics .

complications of salmonella typhi , besides gastrointestinal system , involve nervous system , bone marrow , kidneys , and heart.[13 ] empyema thoracic due to s. typhi is a rarely reported complication , and most of the case reports are from adults . although respiratory symptoms are common , empyema thoracic is a rare occurrence in s. typhi infection . in reviews on cases with atypical manifestation of s. typhi infection , none of the 32 cases presented with empyema thoracic . a review of the literature of past 100 years published in 2005 could find only 14 cases due to s. typhimuruim and 25 cases due to other nontyphi salmonella . a 10-year - old girl with bilateral pleural effusion due to s. typhi with high - level of ciprofloxacin resistance has been reported recently in the year 2010 . we herein report an 18-month - old immunocompetent child with empyema thoracic due to s. typhi , sensitive to ofloxacin , an extremely rare occurrence ; as the youngest child reported with this complication till date . an 18-months - old male child presented with history of high - grade fever for 1 month , cough for 15 days and progressive breathlessness of 7 days duration without relief of symptoms by medications prescribed by a local medical practitioner . history of loose stools , vomiting , significant weight loss , and contact with tuberculosis were absent . he was a predominantly breast fed baby , and his mother had been suffering from fever 2 months back , which responded to 10 days of antibiotic therapy . on examination , it was seen that he was acutely ill , irritable , pale , and febrile ( temperature 39 c ) . ( > 2 sd as per who growth charts ) ; the heart rate was 130/min ; respiratory rate was 60/min with intercostal recession along with diminished air entry on the left side . diagnosis of left - sided pleural effusion was made and the same was confirmed on chest x - ray [ figure 1a ] . pleural tap was done and 150 ml of viscid purulent fluid was aspirated . x ray chest showing left sided pleural effusion . cell count of pleural fluid revealed a total of 6800 cells / mm ( 84% polymorphs and 16% lymphocytes ) and proteins of 4.6 gm / dl . intercostal drain ( icd ) was placed and intravenous ceftriaxone and vancomycin was started empirically . the organism was further confirmed using serotyping method and the confirmed s. typhi was reported along with antibiogram . ceftriaxone alone was continued . blood and stool cultures were sterile and widal test was positive ( o titer of 1:120 and h titer of 1:240 ) . hemoglobin was 8.8 gm% and total leucocyte counts was 20,500 ( polymorphs 78% , lymphocytes 20% , eosinophils 2% , ) . liver function tests , renal function tests , serum electrolytes , iron profile , sickling test , and ultrasound abdomen were normal . intercostal drainage tube was removed after 5 days when no drainage was seen from the tube . however , even after 10 days of antibiotic therapy fever was persisting and x - ray chest was still hazy ; therefore , a ct thorax was done that revealed loculated pus in the left pleural cavity [ figure 1b ] . based on pleural fluid culture sensitivity report after 6 days of further treatment , the patient became afebrile and chest x - ray improved markedly with a total of fourteen days of ofloxacin therapy [ figure 2 ] . elisa for hiv of both child and mother were negative and immunoglobulin profile ( igg , iga , and igm ) of the child were normal . the patient was doing well during a year 's follow up . to find out the source of infection in this child we investigated his mother , and performed cultures of her blood , urine , stool , and breast milk . mother 's stool culture was positive for s. typhi , and other cultures were sterile . a course of amoxicillin was prescribed for treatment of her carrier status and repeat stool culture after a month of follow up was sterile . enteric fever caused by salmonella group of organisms is an endemic infection in india with more than 0.3 million cases occurring every year . it has been reported to occur in 1020% of children less than 2 years of age . usual symptoms in children less than 2 years are fever ( 100% ) , cough ( 40% ) , diarrhea ( 35% ) , and vomiting ( 28% ) . common complications reported in the literature amongst children with salmonella infection include encephalopathy , meningitis , chorea , gastrointestinal perforation and hemorrhage , myocarditis , shock , hepatitis , cholecystitis , acute renal failure occurring in 9.5% to 37% of these patients.[1310 ] in a series of 42 children of less than 2 years of age with enteric fever , complications were reported in only four children ; these included two cases of encephalopathy and ileus each . extra intestinal involvements due to these organisms are encountered less frequently , but if they are , most of these occur in immune - compromised children . empyema thoracic due to salmonella is extremely rare , even in the presence of underlying co - morbid illnesses such as lung disease , malignancy , diabetes , sickle cell anemia , or alcohol abuse and almost all of these case reports are due to nontyphoidal salmonella . on reviewing literature we could find only five cases of empyema thoracic due to s. typhi.[81215 ] four of these children had some associated condition such as splenic abscess , sickle cell anemia , protein energy malnutrition , and anemia except a case by mohanty et al . who previously had no other associated medical condition . thus , we believe that the present case is the youngest child with s. typhi empyema thoracic who had no underlying immunodeficiency / co morbid conditions . the present case probably got the s. typhi infection from mother . the involvement of pleura in this child could have been either hematogenous or transdiaphragmatic spread from an abdominal focus . this case is interesting as he was immuno - competent and yet developed empyema thoracic in the absence of underlying lung disease or any other co - morbid condition at a very young age . underlying immunodeficiency or co morbid condition may not always be required for salmonella organisms to present as empyema thoracic . in the era of antimicrobial drug resistance , awareness about this atypical presentation of salmonella typhi is essential to initiate a prompt laboratory diagnosis and treatment .

we herein report an 18-months - old child who presented with high - grade fever , cough , and breathlessness along with tachypnoea and diminished air entry on the left side of the chest , in which a diagnosis of left - sided pleural effusion was made . salmonella typhi was isolated from the pleural tap culture . the patient had uneventful recovery with appropriate antibiotic therapy . empyema thoracic as a complication is extremely rare in the absence of an underlying co - morbid illness , is even more uncommon in a child , and is even rarer to find with salmonella typhi species . after reviewing the available literature we could find only five cases of empyema thoracic due to salmonella typhi in children with the age range of 913 years . we are reporting this case as the youngest child reported with this complication .

the inhalational anaesthetic agents presently available are metabolised only to a small extent and are largely exhaled unchanged . this property can be taken advantage of , to perform successful , economic and safe low flow anaesthesia ( lfa ) . the aim of our survey was to get data on the current practice of lfa in india . the amount of volatile anaesthetic agents extracted is directly proportional to the fresh gas flow ( fgf ) into the breathing circuit and system . when high fgf are used , 90% of the volatile agents are unused and are emitted as waste anaesthetic gases ( wag ) into the operation theatre ( ot ) environment or to the atmosphere , exposing those in the ot to health hazards and adding on to the greenhouse effect as well as ozone depletion . a survey on lfa found that the routine use of lfa would circumvent the initial expenditure in months by saving on expenses on volatile agents and carrier gases . another study found that educating the anaesthesiologists was very effective in reducing the fgf rates used thereby contributing to overall cost reduction of anaesthesia . in a geostatistical assessment of anaesthetic gases in ot and exposure to staff , high average concentration of nitrous oxide ( 8445 ppm with peak 1345 ppm ) was detected with high occupational hazard potential for staff in ot . gas scavenging is the most practical way to control or remove wag from ot environment . it is the responsibility of the institution to provide effective scavenging system or continuous flow fresh air ventilation systems to prevent waste gas accumulation in the ot environment , as well as to organise and document a programme of maintenance and checking of all anaesthetic equipment . questionnaires on the use of lfa and the choice of inhalational anaesthetic agents were distributed among 200 anaesthesiologists who visited a business promotion stall during the national conference of indian society of anaesthesiologists . the questionnaire was validated by collecting data from anaesthesiologists working in our centre . from the same group of anaesthesiologists , the difference between the survey responses at these time intervals was tested and found to have no significant difference . this , validated the questionnaire and we found it to be reliable . the questionnaire contained sixteen questions pertaining to the demography , practice of lfa , routine use of workstations , scavenging systems , gas analysers and choice of volatile agents as well as carrier gas preference . the questionnaire contained two parts , the first part intended to collect general information such as years of experience in anaesthesia , region of practice , subspecialty of the participant if any and the practice setting of the participant . the second part dealt with questions specific to the practice of lfa , use of oxygen analysers and agent analysers , routine use of etco2 monitors and bispectral index ( bis ) monitors , type of anaesthesia machine being used routinely , preferred carrier gas and volatile agent as well as the volatile agent in routine use [ appendix 1 available online ] . survey responses were analysed using statistical package for the social sciences version 11 , by spss inc . categorical data were analysed using pearson 's chi - square test and fisher 's exact test and was considered statistically significant if p < 0.05 . a total of 166 questionnaires were returned , making a response rate of 83% . of these two were omitted due to the disparity in facts presented , thus obtaining a response rate of 82% . demographic variables the maximum number of respondents to our survey were in the early years ( 05 ) of anaesthesiology practice ( 42% ) . response analysis showed that 52.4% were from south india whereas 39% were from north india , with a skewing of response population to south india . the question on practice setting of the respondents yielded responses as 48.7% practicing in the general surgery setup , 37.8% respondents practicing paediatric anaesthesia and other subspecialties together accounted for 23.6% . responding to the question on routine practice of lfa , 73.8% of the respondents practiced lfa routinely [ figure 1 ] . regarding the use of low flow routinely in government hospitals , our survey revealed that 63% of those who practiced in teaching government hospitals practiced lfa . of those respondents who used low flows routinely , 31.9% used a low flow rate of 0.51 l. of the respondents who claimed to use low flows , 10.4% were using flows more than 2 l , which does not qualify as low flow [ figure 2 ] . regarding reduction of flows , 48.5% reduced the flows after 10 min of induction while 32.1% reduced the flows after 15 min . most of the respondents ( 44.5% ) used oxygen concentration of 3040% whereas 26.8% used 4150% o2 concentration . routine practice of low flow anaesthesia fresh gas flow rates during routine use of low flow anaesthesia oxygen analysers were used by 50.6% respondents while using low flows whereas agent analysers were used by only 36% . of the respondents , 54.8% preferred nitrous oxide as their carrier gas while performing general anaesthesia ( ga ) . workstations were available for performing lfa for 64.6% anaesthesiologists and minimum alveolar concentration ( mac ) values were displayed by 43.9% of the machines used . analysis of our data showed that of the 32% respondents from government teaching hospitals who performed lfa only 27% had workstations to perform the same , revealing that 5% of those who used low flows were lacking adequate facilities to conduct the same . there seemed to be a paucity of workstations , especially in the nonteaching government hospitals . only 33% of respondents worked in a setup with scavenging systems [ table 2 ] . of those who practiced low flow in paediatric setting , 50% had agent analysers whereas 98% used etco2 monitoring and 20.6% bis monitoring . the maximum percentage of the respondents used fgf at the rate of 0.51 l and 56% used o2 concentration of 3040% [ table 3 ] . availability of workstations , scavenging systems and minimum monitoring equipment for anaesthesiologists practicing low flow anaesthesia in india practice of low flow anaesthesia in paediatric subspecialty by survey respondents and monitoring facilities utilised by them the use of etco2 , oxygen analysers , agent analysers and bis monitoring were compared between the government and private setup using chi - square test and no statistically significant difference was found . the concentration of o2 used during lfa in both government as well as private setup was also analysed using fisher 's exact test and found to have no statistical difference ( p = 0.584 ) . on routine overall use of volatile agents , 55.5% said they used sevoflurane , 54.7% used isoflurane,30.3% used halothane and 11% used desflurane [ figure 3 ] . when asked about the agent of their choice , 32.9% preferred sevoflurane , 15.2% preferred isoflurane and only 1.2% preferred halothane . volatile agents routinely used ( some respondents chose more than one volatile agent as routinely used ) with the availability of sophisticated and modern anaesthesia workstations anaesthesiologists can practice safe lfa , cutting down the economic burden as well as contributing to a greener earth . we conducted this survey to collect evidence on the practice of lfa in india as we found lack of surveys on this practice in indian setup . the practice is prevalent among anaesthesiologists of india with no statistically significant difference between government and private sectors . even now , there is a significant number who do not practice lfa in india ( 26.2% of respondents ) . high flows without scavenging system is a far from ideal situation posing significant health , financial and environmental risks . analysis of our survey results revealed that there are lacunae in concepts regarding true lfa as 10.4% respondents answered that they used > 2 l flows and still were under the impression that they were performing lfa . lfa starts with high flows of 46 l / min and then is reduced to 1 l / min after 10 min . for minimal flow anaesthesia how long after induction are flows reduced , 48.5% responded that they reduced flows after 10 min , which is in accordance with the teaching of lfa . of the respondents , 32.1% decreased the flows in 15 min whereas 15.7% in 20 min . the more reliable method has to be one based on mac and the end tidal concentration of gases , including volatile anaesthetic agents . during anaesthesia initially , the uptake of n2 o and volatile agents are high and decreases with duration of anaesthesia . once the fgf is reduced , an inspiratory oxygen concentration level of 30% can be maintained with a fresh gas o2 concentration of 5060% . on querying about o2 concentrations used routinely with low flows , 45.1% responded that they still use 3040% o2 concentration in fresh gas flow . the minimum monitoring required for lfa include the use of oxygen and agent analysers , inspired and expired co2 monitoring , monitoring minute ventilation and peak pressure . to know the monitoring standards while using low flows , we included questions on the use of agent and oxygen analysers and use of etco2 and bis . evaluation of survey responses reveal that there is a paucity of monitoring equipment as well as provision of modern workstations and scavenging systems in our country which may be an obstacle in practicing lfa safely [ table 2 ] . nitrous oxide is used in current anaesthesia practice primarily to facilitate a reduction in the use of opioids and other anaesthetic agents and to facilitate quicker induction when newer inhalational agents are unavailable . when using air as a carrier gas during lfa , a mild increase in the concentration of the inhaled anaesthetic agent ( 0.20.25% of mac value ) is to be used . bis monitoring is desirable when air is used as a carrier gas for detection of intraoperative awareness . nitrous oxide is still the preferred carrier gas for 54.2% respondents . n2 o accounts for around 6% of the heating effect of greenhouse gases in the atmosphere . the national institute for occupational safety and health , usa recommend 25 ppm as recommended exposure limit for n2 o ( for 8 h ) . there is a lack of use of scavenging systems in most of the ots in india as revealed by our survey . all gases delivered from the anaesthesia machine are released to the atmosphere which adds to the greenhouse effect . the molecules of halothane , isoflurane and enflurane pass to the stratosphere where they are dissociated by the uv radiation to release free chlorine that acts as a catalyst in the breakdown of ozone . although the contribution to the global release is very small from anaesthesia practice , we have a clear duty to minimise the release of these chemicals into our atmosphere . the atmospheric lifetimes of desflurane are 21.4 years , sevoflurane 1.4 years and isoflurane 3.6 years . as revealed by our survey results , although only 3% opted for halothane as their agent of choice , 30.3% were forced to use halothane routinely , most probably because there were no alternatives in their workplace . provision of modern anaesthesia workstations with mac monitoring is essential to the safe and successful practice of lfa . around 80% of the respondents had workstations although mac value display was available only for 43.9% respondents . the initial investment cost of workstations with agent analysers and scavenging system may be an obstacle for the widespread practice of lfa in our country . ryan and nielsen in their article on global warming potential of inhaled anaesthetics have suggested methods to reduce the environmental pollution by a certain change of practice by anaesthesiologists such as avoiding n2 o use and using low flows . the limitations of the study were that , as the conference was conducted in south india , there is a skewing of population to the south , and second , the cross section who participated in the survey itself is very small . in future , more information can be gathered by more institution based studies comparing the cost effectiveness of lfa in india . continuing education , feedback enquiries and hospital and government implemented guidelines can contribute to better and safe anaesthetic practices in our country . our survey revealed that low flow anaesthesia is being practiced in india by many anaesthesiologists . there is a lack of adequate monitoring facilities and scavenging systems . in a large country like ours , with lots of health care facilities performing surgeries under general anaesthesia , our role in adding to global warming and ozone depletion

background and aims : with the availability of modern workstations and heightened awareness on the environmental effects of waste anaesthesia gases , anaesthesiologists worldwide are practicing low flow anaesthesia ( lfa ) . although lfa is being practiced in india , hard evidence on the current practice of the same from anaesthesiologists practicing in india is lacking and hence , we conducted this survey.methods:a questionnaire containing 16 questions was distributed among a subgroup of anaesthesiologists who attended the 2014 national conference of indian society of anaesthesiologists . the filled - in questionnaires were computed and analysed with spss version 11.results:the response rate to the survey was 82% . about 73% of the respondents practiced lfa routinely , with 65% having workstations . most of the anaesthesiologists used fresh gas flows < 1.5 l / min with 45.1% using o2 concentrations at a range of 3040% . etco2 monitoring was used routinely by most whereas use of agent analysers and bispectral index monitoring were restricted . the availability of scavenging system was also limited to only 33.5% . majority preferred n2 o as carrier gas and sevoflurane as volatile agent of their choice.conclusion:our survey revealed that practice of lfa in india has numerous lacunae . provision of better monitoring facilities , workstations as well as awareness regarding the environmental issues of waste anaesthetic gases need to be addressed .

when first described by gaglio in 1886 , measurement of lactate levels required the collection of 100200 ml blood and took several days to complete . the labour - intensive nature of early lactate measurement techniques limited their clinical use , because results were not available until long after therapeutic decisions had to be made . in 1964 broder and weil were the first to use a photospectrometric method to measure lactate levels in whole blood decreasing turnaround times greatly . current handheld devices and mobile blood gas analyzers have decreased turnaround time to less than 2 min using a minimal amount of blood . with this technology it is possible to diagnose , treat and monitor critically ill patients rapidly and easily . a relationship between increased blood lactate levels and the presence of oxygen debt ( tissue hypoxia ) in patients with circulatory shock was suggested as early as 1927 . in patients with clinical shock , associated with tachycardia , hypotension , cold and clammy skin and decreased urine output , lactate levels have been referred to as the best objective indicator of the severity of shock . can increased blood lactate levels serve an indicator function in patients without clinical signs of circulatory failure also ? if so then what would increased blood lactate levels in these circumstances indicate , and what would be the most appropriate therapy in these patients ? the circulation is a demand driven system in which increases in oxygen demand are met by increases in oxygen delivery through increases in blood flow . tissue hypoxia can thus be defined as a state in which tissue oxygen demands are not met by tissue oxygen delivery . decreases in haemoglobin levels and arterial oxygen saturation are usually compensated for by an increase in cardiac output to maintain global oxygen delivery , and so tissue hypoxia usually does not occur . when cardiac function is limited this compensatory mechanism fails and tissue hypoxia can occur rapidly . many experimental and clinical studies have shown that blood lactate levels start to rise when tissue hypoxia occurs [ 8 - 11 ] . because blood pressure is maintained over a rather wide range of cardiac output values , limited compensatory increases in cardiac output may fail to be noticed clinically , and thus the presence of tissue hypoxia may not always be noticed . in this issue , meregalli and coworkers show that lactate levels in haemodynamically stable postsurgical patients discriminated between survivors and nonsurvivors within the first 12 hours of admission , despite similar global haemodynamics in both patient groups . these and other authors refer to this situation of hyperlactataemia in the presence of stable haemodynamics as a state of occult hypoperfusion . although cardiac output and blood pressure did not 1 change intraoperatively , lactate levels increased . following surgery cardiac output increased , and those authors suggested that this represented physiological compensation for the intraoperative oxygen deficits , because a significant linear relationship between calculated intraoperative oxygen deficit and lactate levels was found in that study . in a study conducted by smith and coworkers ( 50% of patients studied were surgical patients ) , those investigators showed that patients with increased blood lactate levels on admission had significant mortality ( 24% ) , even when blood lactate levels normalized within the first 24 hours . when increased blood lactate levels on admission could not be normalized within 24 hours , mortality in these patients increased to 82% ( fig . the ' silver day ' of trauma resuscitation , blow and coworkers showed that normalizing blood lactate levels within 24 hours of admission in haemodynamically stable trauma patients was associated with improved survival . resuscitation in these patients was aimed at improving global blood flow whenever lactate levels remained above 2.5 mmol / l . both morbidity ( organ failure ) and mortality were increased among those patients in whom blood lactate levels failed to normalize with these therapeutic efforts . in patients with major trauma , claridge and coworkers showed that occult hypoperfusion was associated with an increased rate of infection and mortality . in patients with a femur fracture , crowl and coworkers showed that patients with occult hypoperfusion , defined as an increased blood lactate level , had no clinical signs of shock . abramson and coworkers showed that normalization of lactate levels within 24 hours after resuscitation aimed at increasing oxygen delivery , and cardiac output was associated with a 100% survival . in patients requiring 2448 hours to normalize lactate levels , mortality was 25% . none of the patients with increased blood lactate levels at 48 hours survived . only one prospective study has shown that normal lactate levels as a therapeutic goal in surgical patients ( cardiac surgery ) and a resuscitation protocol aimed at increasing oxygen delivery ( mainly cardiac output ) was associated with improved outcome ( morbidity ) in the protocol group . from these studies it is clear that increased blood lactate levels in critically ill surgical patients are not always related to clinical signs of circulatory failure . treatment aimed at increasing oxygen delivery ( usually aimed at increasing cardiac output ) can normalize blood lactate levels in these patients . failure to normalize increased blood lactate levels with these interventions is generally associated with increased morbidity and mortality . limited prospective data are available , but these data also indicate that maintaining normal blood lactate levels or rapid normalization of increased blood lactate levels is an important therapeutic goal in critically ill patients . adequate fluid resuscitation and inotropes to increase cardiac output have consistently been found to improve tissue oxygen delivery in patients with tissue hypoxia , and thus remain the mainstay of therapy in these circumstances [ 20 - 24 ] . where allardyce and coworkers urged referral centres for critically ill surgical patients to monitor blood lactate levels , we would urge clinicians to monitor lactate levels in all patients at risk for ( occult ) hypoperfusion related either to decreases in oxygen delivery or to increases in oxygen demand . both in patients with normal and in those with increased blood lactate levels on admission , changes in blood lactate levels during the first 24 hours of treatment were related to ultimate survival .

both in emergency and elective surgical patients increased blood lactate levels warn the physician that the patient is at risk of increased morbidity and decreased changes of survival . prompt therapeutic measures to restore the balance between oxygen demand and supply are warranted in these patients .

esophageal achalasia is a rare motility disorder of the esophagus involving the smooth muscle layer and the lower esophagus sphincter ( les ) , with its incomplete relaxation and increased tone . this pathology is characterized by difficulty in swallowing , regurgitation , and sometimes chest pain . specific tests for diagnosis of esophageal achalasia are barium swallow and esophageal manometry . esophago - gastro - duodenoscopy with or without endoscopic ultrasound can be also performed to rule out the probability of cancer . for management , dilation or stretching of the esophagus , surgery and injection of muscle relaxing substances ( botulin toxin ) in the esophagus were foreseen . we present a case of esophagus achalasia diagnosed for intense rest and effort dyspnea , persistent cough , arterial hypotension , and chest discomfort . 12-leads ecg showed sinus rhythm with pulse rate at 95 beats / min . left axial deviation and diffuse disorders of repolarization were also seen . chest x - ray revealed massively dilated esophagus along the right cardiac border [ figure 1 ] . ct of the chest showed esophageal body dilatation filled with food remaining that compressed the left atrium [ figure 2 ] . the esophageal manometry evidenced body esophageal a - peristalsis , with low amplitude of esophageal body contraction and failed relaxation of les after water swallow . left atrial compression induced by an extrinsic structure was seen at two - dimensional - trans - thoracic echocardiography ( 2d - tte ) . this structure has an elongate form and was filled of liquid drinking to differentiate esophagus from any cardiac formation [ figure 3 ] . diastolic mitral inflow pattern showed an e / a waves ratio = 1.1 ; dt measured 210 msec . ; ivrt was 87 msec . three dimensional echocardiography ( 3d - tte ) pointed out the extracardiac roundish esophageal cavity compressing left atrium , clearly separated from the heart structures [ figure 4 ] . the same evaluation performed in parasternal approach ( at level of aortic root ) consented to identify the pulmonary trunk and its subdivision in right and left pulmonary arteries [ figure 5 ] . antero - posterior chest x - ray that shows poorly defined borders at the median and lower right lobe and at the lung base ct of the chest pointed out extrinsic compression at level of the left atrium by dilated esophagus ( arrow ) two - dimensional echocardiography recorded in apical 4 chambers view showing an extrinsic compression on the left atrium due to a dilated and lengthened formation evidenced after drinking a liquid ( arrow ) ( a ) three - dimensional echocardiography performed in apical 2-chambers view . evidence of a round structure ( arrow ) compressing left atrium ; ( b ) three - dimensional echocardiography in the same approach . more evident dilated esophagus ( arrow ) located below to the cardiac plane and separated from the cardiac structures three - dimensional echocardiography performed from the parasternal approach intermediate between the long and short - axis view , at level of aortic root . clear evidence of dilated esophagus ( arrow ) compressing the lower segment of the pulmonary trunk the symptoms are a consequence of the left atrial compression that reduces its volume causing an impairment of left ventricular diastolic filling . in addition , as a consequence of increased left atrial pressure , pulmonary pressure also rises causing an intense dyspnea leading to pulmonary edema . esophageal achalasia is usually diagnosed by chest x - ray , ct , mri , and esophageal manometry . functional magnetic resonance imaging ( fmri ) has been recently proposed for the evaluation of the esophagus motility . but , the test of choice for diagnosing its extrinsic compression of left atrium by esophageal achalasia is two - dimensional echocardiography ( 2d - tte ) . at 2d - tte , the achalasia moves asynchronously with the atria in contrast to intrinsic atrial structures . in our case , 2d - echocardiography performed in apical long - axis view evidenced the compression of left atrium by an extracardiac structure corresponding to the dilated esophagus evidenced by the liquid drink . nevertheless , 2d - tte is limited to the cases with acceptable sonographic window . in the presence of a poor sonographic space , trans - esophageal echocardiography three - dimensional trans - thoracic echocardiography ( 3d - tte ) was also performed in our patient . this was firstly carried out in an individual with esophageal achalasia . in our patient , 3d - tte records consented to better appreciate the esophagus compressing the left atrium and the lower part of the pulmonary trunk . even though 3d - tte is not explanatory than 2d - tte , it consented to better evaluate the dilated esophagus separated from the left atrium and compressing this same and some neighboring structures without the liquid drink too

esophageal achalasia is a motility disorder characterized by impaired relaxation of the lower esophageal sphincter and dilatation of the distal two - thirds of the esophagus . this condition may be a non - frequent reason of extrinsic compression of left atrium . in turn , this can be a cause of some hemodynamic changes such as chest discomfort , dyspnea or reduced exercise tolerance , systemic hypotension and tachycardia . we describe a case of a patient with esophagus achalasia compressing the left atrium and inducing hemodynamic compromise . the diagnostic methods , as chest x - ray , computed tomography ( ct ) , manometry , and 2d - trans - thoracic echocardiography ( tte ) demonstrated the esophagus dilation , the impaired relaxation of the lower esophageal sphincter , and its compression on the left atrium . three - d trans - thoracic echocardiography ( 3d - tte ) was firstly performed also . this last examination pointed out better than 2d - tte the extrinsic compression of the left atrium due to the esophagus dilatation . therefore , 3d - tte is a true improvement for the echocardiographic diagnosis of the left atrial compression induced by esophageal achalasia .

the assessment of orthodontic treatment need and complexity is necessary for the planning of orthodontic services in any given population , as well as training programmes for specialists . occlusal indices , such as the index of orthodontic treatment need ( iotn ) and the dental aesthetic index ( dai ) have been used successfully around the world to provide information on orthodontic treatment need in various communities . suggested that difficulty and complexity in orthodontics are synonymous and should be defined as a measurement of skill and effort while severity is a measurement of how far a malocclusion deviates from the normal . meanwhile , cassinelli et al . also reported that complexity or difficulty is related to the severity of malocclusion and increases as the severity of the malocclusion increases . the index of complexity , outcome , and need ( icon ) which was developed based on the expert opinions of 97 practising orthodontic specialists from 9 countries has provided an internationally acceptable means of measuring orthodontic treatment need , complexity and outcome with a single measurement protocol . the index comprises five components : the aesthetic component of the iotn ( ac ) , amount of maxillary crowding or spacing , the presence or absence of crossbite , incisor open bite / overbite , and anteroposterior buccal relationship which are weighted as follows : ac ( 7 ) , maxillary crowding or spacing ( 5 ) , crossbite ( 5 ) , incisor overbite / open bite ( 4 ) , and anteroposterior buccal relationship ( 3 ) . the components are measured , multiplied by their respective weights , and summed up to give an overall score . the cut - off point for treatment need complexity values are graded from easy to very difficult , depending on the score obtained . in southwestern nigeria , various studies have been carried out to assess the prevalence of malocclusion , though a large majority [ 714 ] were purely descriptive qualitative studies . other studies on orthodontic treatment need have equally been done with the index of orthodontic treatment need ( iotn ) and the dental aesthetic index ( dai ) [ 1521 ] . meanwhile the index of complexity , outcome , and need ( icon ) has also been used to determine orthodontic treatment need and complexity both in the general population and in patients attending orthodontic clinics [ 2224 ] . generally , research , clinical practice , and specialist training in southwestern nigeria as it relates to orthodontics is much more advanced , as compared to rivers state located in south - south nigeria , where the specialty is relatively new . outside the studies in ibadan city of nigeria , the authors search did not reveal any literature from other parts of nigeria that assessed both orthodontic treatment need and complexity using the icon . moreover , icon has been validated for the nigerian population , shown to be useful in assessing orthodontic treatment need and complexity [ 22 , 23 ] and to be effective for assessment of different facets of orthodontic provision , when compared with previously existing indices . therefore , the aim of this epidemiological study was to estimate the need for and the complexity of orthodontic treatment among 12 to 18 year - old schoolchildren in rivers state , nigeria , using the icon . this is the first time such a study is being carried out in this part of nigeria , and documentation of such important statistics will thus allow for informed planning of orthodontic services in this region . there are 23 local government areas ( lgas ) in rivers state of nigeria due to security concerns at the time this study was being carried out ; permission was granted by the rivers state ministry of education for 12 lgas , comprising 2 urban and 10 rural , out of which six were selected by ballot , consisting of one urban lga ( port harcourt ) and five rural lgas : ikwerre , omumma , tai , okrika , and asari - toru . out of the list of schools obtained from the rivers state ministry of education one school was selected by ballot from each of the six lgas making a total of six schools . the students were randomly selected from each of the schools and the sample population consisting of 612 students with age range of 12 to 18 years was obtained comprising 299 ( 48.9% ) males and 313 ( 51.1% ) females . the researcher was calibrated in the use of the icon using dental casts by a senior colleague ( coo ) who is trained and experienced in the use of the index . an intraoral examination of the participating students was conducted by the researcher in the selected school compounds using natural illumination and strictly following the guidelines of the icon . the need for orthodontic treatment was defined as an icon score of 43 and above while complexity was graded into easy ( < 29 ) , mild ( 2950 ) , moderate ( 5163 ) , difficult ( 6477 ) , and very difficult ( > 77 ) in line with icon guidelines . sixty - two of the students were selected randomly and reexamined by the researcher after a four - week interval . the reproducibility of the icon scores were assessed using spearman 's rank correlation coefficient ( p = 0.98 ) , and excellent agreement was found . intraexaminer consistency for the categorisation of treatment need into need and no need was expressed as the kappa reliability coefficient with a value of 0.93 indicating strong agreement , whilst the reliability of the complexity grades was also evaluated using w kendall test with a value of 0.78 . the data was analyzed statistically using the spss statistical package ( statistical package for the social sciences version 17.0 for windows 2009 , spss , inc . , the quantitative variable icon score , mean for central tendency and standard deviation were used . for the ordinal variables , icon categorization of treatment complexity , number ( frequencies ) , and percentages male and female subject differences with respect to icon score were tested using student t - test . to test for any dependence on gender of complexity grades , the mean age of the studied population was 15 2.0 years ; male was 14.9 1.9 years and female was 15.0 2.0 . about thirty - eight per cent ( 38.1% ) of the studied population had a need for orthodontic treatment with a mean icon score of 39.7 25.3 . there were statistically significant gender differences , the mean icon score was higher in males ( 43.1 26.3 ) than females ( 36.3 23.8 ) ( p = 0.001 ) , and a higher number of males ( 43.5% ) than females ( 32.9% ) were found to be in need of orthodontic treatment ( table 1 ) . statistically significant age differences were also determined ; twelve- and thirteen - year olds were less likely to have a treatment need ( odd ratio = 0.58 ) , while 17-year olds were found to be more likely to have need for orthodontic treatment ( odd ratio = 1.82 ) when compared with the other age groups ( p = 0.04 ) ( table 2 ) . easy complexity was found in 42.6% of the population , 28.3% had mild complexity , 7.5% moderate complexity , whilst 10.3% and 11.3% had difficult and very difficult grades of complexity , respectively . there were significant differences between complexity grades in males and females ( p = 0.02 ) ( table 1 ) , with twice as many males ( 15.1% ) with very difficult complexity grades as females ( 7.7% ) and more female ( 47.3% ) than male students ( 37.8% ) found to have easy categories of treatment need . as the level of complexity of the malocclusion increased , a corresponding increase in treatment need was seen ( table 3 ) . of the students assessed to have a need for treatment ( 38.1% ) , none of them was found to have malocclusions of easy complexity while students without a treatment need did not have malocclusion that was categorized to be difficult or very difficult to treat . the mean icon score of 39.7 25.3 obtained in this study was slightly lower than that obtained for a similar nigerian population of 12- to 18-year olds ( 41.93 15.38 ) . however , this study involved a larger sample size , and thus a wider range of occlusion was assessed . likewise , the mean icon score recorded in our study was also lower than the values obtained in prevalence studies on 12- and 13-year olds in latvia ( 42.05 ) and senegal ( 42.3144.46 ) and 1114 year - old iranian schoolchildren ( 44.6 24.83 ) . these differences could be due to the wider age range of the population whilst racial variations may also be a factor . just over a third of the population in this epidemiological study was found to have a need for orthodontic treatment according to the icon ( 38.1% ) . this is comparable to the value ( 35.3% ) obtained for children in latvia but lower than 42% obtained for adolescents in western nigeria [ 24 , 29 ] , 44.1% in senegal , and 46.6% reported among 1114 year - old iranian schoolchildren . studies conducted on orthodontic patients , however , with values of 82.1% in nigeria , 94% and 86% in greece and united states of america [ 25 , 31 ] , respectively , have a much higher need for treatment than obtained in this study . this is expected because these studies were clinic - based and involve patients with recognised needs for treatment that brought them to the orthodontists . the increase of orthodontic treatment need with age seen in this study is probably due to the fact that untreated malocclusion worsens with age as the permanent occlusion becomes established . when assessed professionally , male adolescents had a significantly greater need for treatment than females which is consistent with the findings of burden et al . , but inconsistent with the finding by onyeaso in a clinic - based study in southwest nigeria where clinical research has shown that more females recognise a need for orthodontic treatment than males . these findings , however , are in contrast to other studies to assess orthodontic treatment need using the icon , dai , and iotn conducted in nigeria [ 15 , 29 , 34 ] , tanzania , senegal , france , kuwait , latvia , and iran where there were no gender or age differences . very difficult and difficult complexity grades of malocclusion accounted for almost a quarter of the adolescents ( 21.6% ) which was similar to values obtained in iranian schoolchildren ( 26% ) but in sharp contrast to that obtained among adolescents in western nigeria ( 9.9% ) and 10% in latvia . the majority of adolescents with malocclusion can be greatly reduced by intercepting and treating during childhood . in the iranian study , only 1.1% of the studied population wore an orthodontic appliance , which indicates a dearth of interceptive orthodontics among iranian children . such is the case in rivers state , where none of the children wore an appliance , and it is just recently that such services started at the university of port harcourt teaching hospital in the state . much higher values were obtained in previous clinic - based studies in nigeria , greece , and united states of 60.7% , 61% and 60% , respectively , due to the fact that these are orthodontic patients with obvious needs for treatment . moderately complex cases in this study were the least in number ( 7.5% ) which is quite low compared with values from other prevalence studies , 16.1% in nigeria , 14.1% in latvia , and 15.1% in iran . this value is also much lower than that obtained in clinic - based studies carried out in nigeria ( 14.3% ) , greece ( 23% ) , and usa ( 22% ) . mild and easy cases in our study ( 70.9% ) were found to be comparable to the 75% obtained in western nigeria and 76% obtained in latvia , higher than 58.5% amongst iranian schoolchildren , but in contrast to values obtained among orthodontic patients in nigeria ( 25% ) , greece ( 16% ) , and usa ( 18% ) . another finding in this study was the significant difference in complexity grades found between male and female adolescents . twice as many male students ( 15.1% ) had very difficult grades of complexity as compared with the female students ( 7.7% ) . this is similar to the findings in the recent iranian study , where a greater number of male ( 14.8% ) than female children ( 9.1% ) were found to have very difficult grades of complexity of their malocclusions although this was not statistically significant ( p > 0.05 ) , unlike the present study . in this study there were also highly significant associations between orthodontic treatment complexity and need because the higher the complexity grade , the higher the degree of treatment need and the greater the severity of the malocclusion . similar findings have been documented in both epidemiological studies and in orthodontic patient populations in earlier studies in ibadan [ 23 , 24 ] using the icon and dai and in a us study . the complexity of cases in a particular location is extremely important because cases classified as very difficult , difficult , and moderate in complexity require the skills of specialists to be adequately treated . [ 4 , 37 ] , as well as onyeaso and begole , found the pretreatment icon score to be a good indicator of treatment difficulty . they reported that cases with higher pretreatment icon scores took a longer time to treat . reported that complexity or difficulty in achieving an ideal occlusion increases as the severity of the initial malocclusion increases . the overall prevalence of orthodontic treatment need among adolescents aged 1218 years in rivers state , nigeria was 38.1% . most of the subjects fell into the easy grade of complexity while about a quarter was found to have difficult and very difficult grades of complexity . as the level of complexity of malocclusion increased , a corresponding increase in treatment need was seen . although no adequate explanation was found , orthodontic treatment need and complexity were found to be significantly higher amongst males and in the older age group . considering the large percentages of adolescents found to have a need for orthodontic treatment as well as difficult and very difficult grades of treatment complexity , we recommend that more attention be given to the training of orthodontic specialists , and that orthodontic care should be subsidised by the rivers state government so that it can become affordable to the majority of these adolescents in need of such care .

introduction . the assessment of orthodontic treatment need and complexity are necessary for informed planning of orthodontic services . the aim of this cross - sectional study was to assess these parameters using the index of complexity , outcome , and need ( icon ) in a nigerian adolescent population in a region where orthodontic services are just being established . methods . six hundred and twelve randomly selected nigerian adolescents aged 12 to 18 years were examined using the icon in their school compounds . descriptive statistics were employed in the data analysis . results . out of a total of 38.1% of the population found to need orthodontic treatment , there were more males and older adolescents . the overall mean icon score for the population was 39.7 25.3 sd with males having statistically higher mean icon score . the grades of complexity of the population were 21.6% for very difficult and difficult , 7.5% moderate , and 70.9% mild / easy . conclusions . although just over a third of the adolescents were found to have a need for treatment , about a quarter of them were found to have difficult and very difficult complexity grades indicating a need for specialist care . the authors recommend the training of more specialist orthodontists in this region .

laparoscopy is an important surgical technique , and an understanding of normal and altered anatomy is crucial for successful surgery . we describe herein a patient in whom the left ureter follows an anomalous course due to previous surgery . this is the case report of a 28-year - old female with a history of ureteral reimplantation evaluated with laparoscopy for dysmenorrhea and infertility . the left ureter followed an anomalous , transperitoneal course , lateral to the fallopian tube , starting at the infundibulopelivc ligament down to its insertion in the bladder . this case describes an anomalous course of the ureter presumed to be due to previous childhood surgery . as more individuals with a history of ureteral reimplantation an understanding of potential anatomic abnormalities will reduce the risk of inadvertent visceral damage at surgery . to avoid inadvertent damage to normal structures , understanding normal and altered anatomy is crucial for the pelvic surgeon . this report describes an anomalous course of the left ureter presumably secondary to previous ureteral surgery . a laparoscopy was performed due to her increasingly severe dysmenorrhea and infertility . at laparoscopy , the uterus , ovaries , and fallopian tubes were normal with bilateral patency of her fallopian tubes . however , her left ureter followed a transperitoneal course starting at the infundibulopelvic ligament and coursing down to the bladder ( figure 1 ) . at approximately 3 cm from its insertion into the bladder the adhesions between the bowel and ureter were released , and the ureter was noted to perforate the ileum about 5 mm from the antimesenteric border of the ileum ( figure 2 ) . an endo - gia stapler ( tyco health - care group , norwalk , ct ) was used to divide the small band of ileum above the ureter , leaving the larger segment of ileum intact . after the small band of bowel was resected , the lumen of the ileum was narrowed but adequate , so a resection and reanastomosis were not necessary . the left ureter with adhered small bowel is noted just lateral to the left fallopian tube and ovary . the ureter is noted to course above the round ligament just before its insertion into the bladder . the probe has been placed through the perforation of the small bowel , just lateral to the ureter . the small band of ileum above the probe was resected with an endo - gia stapler ( tyco health - care group , norwalk , ct ) . laparoscopy is a valuable component in the evaluation of pelvic pain and infertility . as other patients with a history of ureteral reimplantation knowledge of potential anatomic abnormalities , such as the one described in this case report , will help avoid inadvertent trauma to viscera at these future surgeries . late , postoperative , bowel sequelea are uncommon , but include bowel obstruction around a transperitoneal ureteric band and unintended viscera perforation . the international reflux study described 4 of 237 postoperative , ureteral reimplantation patients where the ureter perforated a visceral organ . in 3 of these patients , the perforated organ was the bowel , and in one it was the round ligament . hussain et al described a case of small bowel obstruction caused by strangulation of the bowel around a ureteric band 17 years after ureteral reimplantation . kaufman et al described 2 patients following ureteroneocystostomy with distal ureteral obstruction , one with the ureter perforating the small bowel and the other with the ureter perforating the fallopian tube . this case describes a patient with a history of childhood ureteral reimplantation who underwent laparoscopy for dysmenorrhea and infertility . findings included normal gynecologic organs , with an unrelated finding of asymptomatic perforation of the midileum by the transperitoneal , reimplanted ureter . due to concerns about future , potential bowel obstruction this release was accomplished by dividing and stapling , with an endo - gia stapler ( tyco healthcare group , norwalk , ct ) , the small band of ileum above the ureter and leaving the larger lumen intact and functional . this case is important because it describes anatomic anomalies , knowledge of which will assist the pelvic surgeon in avoiding trauma to normal viscera .

background : laparoscopy is an important surgical technique , and an understanding of normal and altered anatomy is crucial for successful surgery . we describe herein a patient in whom the left ureter follows an anomalous course due to previous surgery.methods:this is the case report of a 28-year - old female with a history of ureteral reimplantation evaluated with laparoscopy for dysmenorrhea and infertility.results:the left ureter followed an anomalous , transperitoneal course , lateral to the fallopian tube , starting at the infundibulopelivc ligament down to its insertion in the bladder . during its transperitoneal course , the ureter perforated the ileum.conclusion:this case describes an anomalous course of the ureter presumed to be due to previous childhood surgery . as more individuals with a history of ureteral reimplantation reach adulthood , an increasing number will require abdominal , surgical procedures . an understanding of potential anatomic abnormalities will reduce the risk of inadvertent visceral damage at surgery .

five marketed formulations of naga bhasma were procured from the new delhi market as per the details mentioned in table 1 . list of drugs and ingredients used in analysis xrd studies were carried out for the detection of phase of lead present and to detect compound type whether crystalline / amorphous in nature . the xrd patterns of the solid samples were recorded on rigaku model x - ray diffractometer using cuk radiation ( =1.5418 a ) filtered by nickel foil over the range of diffraction angle 5.0 to 65.0. the instrument was operated at 40 kv and 30 ma and xrd patterns were recorded at a scanning rate of 2/min . tga was used to determine total weight change in the sample formulations during thermal treatments . an sdt q600 tga / dsc of ta instrument was used to record the weight loss of the samples between 0 and 800. dry nitrogen gas was used as a purge and the scan speed was 10 /min . an isothermal period at 25 was run for 10 min prior to the measurements and any changes in weight during that period were monitored . in all measurements between 5 mg and 10 mg of sample the thermograms obtained from the tga results were analyzed using ta universal analysis nt software . a performance matched platinum / platinum - rhodium thermocouple embedded in each beam ensures accurate and precision transition and differential temperature measurements ( ta instruments manual ) . the dsc was perofrmed using same instrument and the specifications mentioned as above . in all measurements , samples used between 5 mg and 10 mg . samples were placed in open platinum pans and these pans were placed on sample holders . the thermograms obtained for the dsc results were analysed using ta universal analysis nt software . particle size of different formulations were determined by using microtrac s3500 particle size analyzer after suspending a small amount of formulation in aqueous dispersing phase and stirring for 5 min on a magnetic stirrer at room temperature . ftir spectral analysis was used to ascertain the presence of organic matter in the finally prepared drug . ir spectra of all the samples selected for comparative purpose were recorded in kbr pellets in the region 4000 - 400 cm on perkin - elmer ftir spectrophotometer model 1600 . concentrations of different elements i.e. , trace elements and heavy metals present in all formulations were determined using atomic absorption spectrophotometer being one of the most reliable methods of estimation in this regard . in this study , atomic absorption spectrophotometer model aas4141 , electronics corporation of india limited , hyderabad was used for determination of trace elements . the hollow - cathode lamps of al , cu , mg , zn ( ecil ) and ca ( photron ) were employed as radiation source . the fuel used for ca , mg , cu and zn was air / acetylene and for al was n2o / acetylene / air . samples were digested by wet digestion technique and quantitative analysis was carried out using calibration curve technique . xrd studies were carried out for the detection of phase of lead present and to detect compound type whether crystalline / amorphous in nature . the xrd patterns of the solid samples were recorded on rigaku model x - ray diffractometer using cuk radiation ( =1.5418 a ) filtered by nickel foil over the range of diffraction angle 5.0 to 65.0. the instrument was operated at 40 kv and 30 ma and xrd patterns were recorded at a scanning rate of 2/min . tga was used to determine total weight change in the sample formulations during thermal treatments . an sdt q600 tga / dsc of ta instrument was used to record the weight loss of the samples between 0 and 800. dry nitrogen gas was used as a purge and the scan speed was 10 /min . an isothermal period at 25 was run for 10 min prior to the measurements and any changes in weight during that period were monitored . in all measurements between 5 mg and 10 mg of sample the thermograms obtained from the tga results were analyzed using ta universal analysis nt software . a performance matched platinum / platinum - rhodium thermocouple embedded in each beam ensures accurate and precision transition and differential temperature measurements ( ta instruments manual ) . the dsc was perofrmed using same instrument and the specifications mentioned as above . in all measurements , samples used between 5 mg and 10 mg . samples were placed in open platinum pans and these pans were placed on sample holders . the thermograms obtained for the dsc results were analysed using ta universal analysis nt software . particle size of different formulations were determined by using microtrac s3500 particle size analyzer after suspending a small amount of formulation in aqueous dispersing phase and stirring for 5 min on a magnetic stirrer at room temperature . ftir spectral analysis was used to ascertain the presence of organic matter in the finally prepared drug . ir spectra of all the samples selected for comparative purpose were recorded in kbr pellets in the region 4000 - 400 cm on perkin - elmer ftir spectrophotometer model 1600 . concentrations of different elements i.e. , trace elements and heavy metals present in all formulations were determined using atomic absorption spectrophotometer being one of the most reliable methods of estimation in this regard . in this study , atomic absorption spectrophotometer model aas4141 , electronics corporation of india limited , hyderabad was used for determination of trace elements . the hollow - cathode lamps of al , cu , mg , zn ( ecil ) and ca ( photron ) were employed as radiation source . the fuel used for ca , mg , cu and zn was air / acetylene and for al was n2o / acetylene / air . samples were digested by wet digestion technique and quantitative analysis was carried out using calibration curve technique . xrd spectra details represented in table 2 shows the presence of pbo phase in all five formulations in litharge and massicot form whereas three out of five formulations were also found to contain other phases like pb3o4 , pb2o2cl , pbso4 , pb3sb2s6 and pb3(co3)2(oh)2 . maximum peak was found to be of 2 width which denoted that particles are of micron size . maximum peak width is 3 - 5 which denotes that all naga bhasma formulations have amorphous particles . phases of lead present as interpreted by xrd tga plots of five sample formulations showed variable pattern of weight change at different temperatures but significantly between 600-700. weight change was observed in all formulations from -27.5 to + 3.5% w / w . exceptional weight increase was observed in formulation d. details of percentage change in weight are represented in table 3 . total percentage weight loss / gain as interpreted by thermograms variation in endotherms in dsc plots of all formulations reveals that different phases of lead melt or show phase change at different temperatures . a reconstructive litharge ( pbol ) to massicot ( pbom ) phase transformation occurs at temperature range of 525 - 575. all formulations of naga bhasma show various endotherms at different temperatures which suggest presence of lead in different phases . the particle size of the five sample formulations were estimated by automatic particle size analyzer to confirm the presence of micro - size particles observed in xrd studies . the particle size distribution pattern shows a sigmoid curve except in formulation g. formulations a and d have particle size within range of 2 - 52 m and other three have bigger particles than 52 m . particle size range as interpreted by particle size analysis the ftir spectrum denotes the presence of different organic functional groups . all formulations contain tertiary alcohol , dialkyl ketones , secondary amides and 2-substituted pyridines in general . other functional groups present in some are halogens in b , d , g , u ; aldehydes in a , d , g , u ; carboxylic acids in a and g ; and alkyl amine in formulation u. details are represented in table 5 . ftir spectra in all five sample formulations calibration curves were plotted using standard procedure for the estimation of trace elements and heavy metals . estimated concentrations of trace elements and heavy metals trace elements concentration estimated by atomic absorption spectroscopy heavy elements concentration estimated by atomic absorption spectroscopy naga bhasma is a reputed herbomineral preparation in the indian system of medicines and used for various disorders in our body since ages . to scientifically validate this formulation , the present attempt was made to screen five different marketed naga bhasma formulations for their physicochemical properties . the x - ray diffraction studies conducted on these five sample formulations reveal that all formulations of naga bhasma contain lead in pbo ( plumbous oxide ) phase , present in litharge and massicot forms and also other phases viz . pb3o4 form is found present in formulations b , g and u. as per scientific information available , pb3o4 is a compound ( 2pbo.pbo2 ) and can not be used for internal human use as it harms foetus and also significantly impair the fertility system . on that basis moreover , pbo in litharge form is not recommended for internal human use as it causes reproductive disorders and is harmful if inhaled , ingested or come in contact with skin . since the litharge form is found present in all the five sample formulations , it puts a certain question mark over the safety of this formulation . but at the same time the other form massicot was also present in all five samples which is an acceptable form for internal use so this needs to be checked once again whether this formulation was prepared as per the ayurveda text strictly or not . moreover , maximum peak width is of 2 in xrd spectra which denote that particles are of micron size and not nano size as claimed by previous research papers . if sample contains nano size particles then peaks width should be greater than 20. the presence of micron size particles were further confirmed by automatic particle size analyzer . all samples have micron size particles which get entrapped in the crevices of skin and are smooth in touch except some particles of formulations g and u. these analyses are in contrary to previous studies which have reported that after preparing naga bhasma in the laboratories of department of rasa shastra , the particles were obtained as small as 60 nm . formulations a and d contain particles within range of 2 - 52.5 m which is in alignment to estimation reported earlier whereas , formulations b , g and u contain particles as big as 104.7 m , 248.9 m and 176.0 m . tga plots of all formulations show change in weight at different temperatures but show exact change in weight from range 600 to 700. as per scientific knowledge if pure pbo is heated in nitrogen atmosphere up to 600 , it contains substantially more massicot than those heated in air which is more acceptable form for preparing this formulation . however , it was not clear how naga bhasma is prepared by different manufacturers that have shown significant weight changes among themselves i.e. , from -27.5 to + 3.5% w / w . exceptional weight increase was observed in formulation d. so method of preparation of all these formulations can not be the same . ftir studies conducted on these five sample formulations revealed the presence of various organic functional groups viz . tertiary alcohol , dialkyl ketones , secondary amides and 2-substituted pyridines common in all samples whereas some other variable functional groups were also present in some formulations like halogens , aldehydes , carboxylic acids and alkyl amine . it is important to mention here that presence or absence of these different functional groups affect the quality and efficacy of a particular formulation . variation in endotherms in dsc plots of all formulation reveals that different phases of lead melt or show phase change at different temperatures . a reconstructive litharge ( pbol ) to massicot ( pbom ) phase transformation occurs at temperature range of 525 - 575. pbol has tetragonal crystalline dark red color particles and pbom has orthorhombic crystalline bright yellow color particles . this shows that all formulations contain pbo in litharge form in very high ratio which can be potentially dangerous for human health . the presence of pbol and pbom was also confirmed by ishtavarnattwa ( color ) test which show that all samples have different colors ranging from buff color - yellow - dark orange . based on the aas results , it was observed that all marketed naga bhasma sample formulations are rich source of essential elements mg , ca , zn , cu and al . presence of these essential elements may play an important role in maintenance of health and as true revitalizer and energizing formulation . also , the difference in the presence and absence of arsenic and mercury in different formulations clearly show that these naga bhasma are prepared by different methods . percentage of lead in formulations a , b , d , g and u are 1.5 , 3.0 , 2.0 , 4.6 and 5.5% w / w , respectively which are quite variable and sufficient to affect the quality of a drug . however , previous studies suggest that naga bhasma contains approximately 5% w / w of lead ( pb ) when prepared in laboratory . although , present findings risesuncertainity over the safety of this formulation yet variation in the results with all five formulations also indicate that these preparations were not prepared as per the mentioned ayurvedic text . moreover , these ayurvedic formulations have been practised since ancient times , therefore it is suggested and concluded that the manufacturing of these formulations should be regulated strictly before launching them into the market and more scientific studies need to be conducted to establish the final verdict on the safety of this and several other similar formulations .

in the practice of ayurveda , where herbomineral formulations are said to be made biocompatible through specific processes like shodhana and marana , the western medical science on the contrary has raised the safety concerns of these formulations in the recent past . in the present study , comparative physico - chemical analysis of naga bhasma , a herbo - mineral preparation having a reputation of miraculous drug commonly used to treat several health disorders , was carried out using five marketed formulations through analytical methods like differential scanning calorimetry , x - ray difraction , thermogravimetric analysis , fourier transform infrared spectroscopy and also subjected for particle size analysis and estimation of trace and heavy metals to access the safety of these formulation . the results revealed variable observations regarding particle size , metal form and content of lead . the presence of free lead in five different formulations indicated towards the possible risk of severe side effects to the consumer . present findings certainly put doubt over the safety of this formulation but at the same time , variation in the results with all five formulations also indicated that these formulations were not prepared as per the mentioned ayurvedic text . hence , enforcement of strict regulatory guidelines is strongly warranted before launching into the market . further , a series of biological studies need to be conducted before taking any final verdict on the safety of this formulation .

a 35-year - old female patient presented with bilateral visual loss of two days duration ( on 16.12.2009 ) with history of consumption of about 150 ml neem oil five days back ( 12.12.2009 ) in an attempted suicide , for which she was taken to the nearby government hospital . she was admitted and treated with induced vomiting after about 2 - 3 hours of consumption . later patient noticed sudden bilateral visual loss and was referred to us for further ophthalmic evaluation . her fundus examination showed bilateral , hyperemic and edematous discs with extension of edema along the superior and inferior temporal arcuate fibers for about 2 - 3 disc diopters from the disc margins . the veins around the disc were mildly dilated and tortuous [ fig . 1 and 2 ] . right eye fundus picture showing disc edema , venous tortuosity with extension of edema along the superior and inferior arcades for about 2 - 3 disc diopters from the disc margins left eye fundus picture showing disc edema , venous tortuosity with extension of edema along the superior and inferior temporal arcades for about 2 - 3 disc diopters from the disc margins complete hemogram was within normal limits , venereal disease research laboratory ( vdrl ) , hiv1 and 2 were non - reactive . a magnetic resonance imaging ( mri ) scan showed bilateral putaminal regions with altered signal , hypointensities in t1-weighted images , hyperintensities on t2-weighted images and hyperintense on fluid attenuation inversion recovery ( flair ) images suggestive of cytotoxic edema due to tissue hypoxia [ fig . 3 and 4 ] . medical therapy was initiated which included methyl prednisolone 1 g intravenously ( iv ) for three days followed by oral prednisolone 50 mg /day for 11 days along with 1000 g vitamin b12 ( injection methyl cobalamin 1000 g intramuscularly ) every five days for eight weeks . bilateral putaminal regions showed altered signal hypointensities in t1w images hyperintensities on t2w images patient did not show any visual improvement after one week of treatment but pupillary reactions improved . during her subsequent follow - up after about 15 days her vision in both eyes improved to counting fingers 1/2 meters and at one month follow - up vision was 20/200 in both eyes and pupillary reactions were normal in both eyes . . 5 and 6 ] right eye fundus picture showing reduced disc edema left eye fundus picture showing reduced disc edema at two months follow - up her vision remained 20/200 in both eyes and injection methyl cobalamin 1000 g intramuscular was continued . neem oil , also known as margosa oil is obtained from the neem plant ( azadirachta indica a. juss ) . neem oil is used as a traditional medicine in india for various diseases like headache , gastrointestinal disorders , as a male contraceptive , menstrual disorders , asthma etc . neem oil poisoning causes vomiting which occurs within minutes to hours following ingestion of the oil . drowsiness and tachypnea with acidotic respiration followed by recurrent generalized seizures the seizures are usually associated with loss of consciousness and coma . in our case , patient had consumed 150 ml of neem oil which had the following contents : neem oil kernel extract in solvent methanol containing 0.15% , azadirachtin she had bilateral toxic optic neuropathy with exaggerated deep tendon reflexes and extensor plantar reflex . mri scan findings were suggestive of acute toxic encephalopathy and it can be considered as a possible etiology for bilateral toxic optic neuropathy . we treated her with injection iv methyl prednisolone 1 g per kg body weight for three days based on case reports on methanol poisoning .

a 35-year - old female was referred to our hospital with bilateral loss of vision of two days duration . she gave history of consumption of about 150 ml of neem oil five days back . examination revealed no perception of light in both eyes . both pupils were dilated and sluggishly reacting to light . her fundus examination showed bilateral hyperemic , edematous discs and also edema extending along the superior and inferior temporal vascular arcade . magnetic resonance imaging ( mri ) scan showed bilateral putaminal regions with altered signal , hypointensities in t1-weighted images , hyperintensities on t2-weighted , images and hyperintense on fluid attenuation inversion recovery ( flair ) images suggestive of cytotoxic edema due to tissue hypoxia . her vision improved to 20/200 in both eyes with treatment after two months . this is the first case report of such nature in the literature to the best of our knowledge .

bronchogenic cysts are congenital lesions thought to result from abnormal budding of the ventral foregut that occurs between the 26 and 40 days of gestation . this abnormal bud subsequently differentiates into a fluid - filled , blind - ending pouch . otherwise , chest pain , cough , dyspnea , fever , and expectoration if the cysts are infected comprise their symptomatology . diagnosis of bronchogenic cysts is possible with computed tomography ( ct ) that usually shows well - circumscribed lesions of water density . however , half of the cysts have attenuation values of soft - tissue because of viscid mucoid content , making them indistinguishable from neoplasms . in this article , we describe the imaging characteristics and pathological findings in a case of bronchogenic cyst presenting as soft - tissue mass , which was evaluated and diagnosed by endobronchial ultrasound ( ebus ) . an 18-year - old male presented with 2-months history of progressive dyspnea on exertion and persistent non - productive cough . chest x - ray showed a left perihilar mass and the ct scan revealed a well - circumscribed , round homogeneous low - density ( 50 hounsfield units ) mass in the middle mediastinum adjacent to the left main bronchus measuring 5.1 cm 5.8 cm at its maximum , causing over 80% luminal narrowing of both left pulmonary veins [ figure 1 ] . rigid bronchoscopy was performed under general anesthesia followed by the insertion of the fiber - optic bronchoscope , which demonstrated a moderate extrinsic compression of the left main stem bronchus . radial probe of 20 mhz frequency ebus with a balloon ( olympus , um - bs20 - 26r ) was then placed through the working channel of the fiber - optic bronchoscope and this showed a hypoechoic homogeneous lesion compressing the left main stem bronchus suspicious of a cystic mass . fine internal echoes within the lesion suggested it was mainly a viscous fluid - filled cyst . 18-year - old male with progressive dyspnea on exertion and dry cough diagnosed with bronchogenic cyst . contrast - enhanced computed tomography of the chest ( lung window ) shows a well - defined round homogeneous low - density mass in the mediastinum adjacent to the left main bronchus measuring 5.1 cm 5.8 cm at its maximum , causing over 80% luminal narrowing of both left pulmonary veins ( yellow arrow ) . 18-year - old male with progressive dyspnea on exertion and dry cough diagnosed with bronchogenic cyst . endobronchial ultrasound demonstrates a hypoechoic homogeneous lesion compressing the left main stem bronchus suspicious of a cystic mass with surrounding anatomical structures . dlmb : distal left main bronchus , dao : descending aorta , lpa : left pulmonary artery , atr : atrium , mv : mitral valve . patient underwent complete surgical excision of the mediastinal cyst through a left posterolateral thoracotomy and exhibited an uneventful recovery . grossly , the cyst was smooth , thin - walled , and unilocular measuring a maximum of 4.5 cm 3.5 cm 2.5 cm and containing mostly mucous brownish fluid [ figure 3 ] . aspiration of the cyst contents was initially performed to make the cyst technically easier to remove . then , the cyst was carefully dissected free of its mediastinal and pleural attachments , taking care not to leave any residual cyst wall behind . histopathologically , the cyst was lined by respiratory epithelium with areas of sub - epithelial fibrosis [ figure 4 ] . a slight chronic inflammation of the epithelial lining was also noted . microbiologic and cytologic examinations of cyst fluid were negative for any pathogen development or malignancy , respectively . the afore - mentioned findings were consistent with the presence of a bronchogenic cyst . at last follow - up , 2 months post - operatively 18-year - old male with progressive dyspnea on exertion and dry cough diagnosed with bronchogenic cyst . photography the surgically removed mass shows the resected thin - walled and unilocular cyst measuring a maximum of 4.5 cm 3.5 cm 2.5 cm and containing mostly mucous brownish fluid . 18-year - old male with progressive dyspnea on exertion and dry cough diagnosed with bronchogenic cyst . microscopic examination of the mass ( hematoxylin and eosin , 50 ) shows a portion of the cyst wall with respiratory epithelium ( black arrow ) that overlies fibrous tissue and cartilage . bronchogenic cysts are congenital bronchopulmonary lesions derived from an abnormal budding of the tracheobronchial tree during embryonic development . their incidence is estimated between 1:42,000 and 1:68,000 . however , it is difficult to appreciate the incidence of the cysts exactly since some aged patients have lesions that remain forever silent . bronchogenic cysts are the predominant sub - group of mediastinal cysts accounting for approximately 40% according to one series followed by pericardial cysts ( 35% ) , enteric cysts ( 10% ) , and non - specific cysts ( 14% ) . they are typically located near the large airways just posterior to the carina and lined with cartilage and pseudostratified columnar epithelium . though usually found as an incidental finding on a chest radiograph performed for other unrelated conditions , they may cause compression symptoms such as chronic cough , chest pain , and dyspnea or may become infected . the symptoms occur frequently in children since their smaller thoracic volume and malleable airways predispose them to compressive symptoms earlier when the cyst enlarges . as for imaging modalities , mediastinal bronchogenic cyst appears on plain chest radiograph as smooth rounded opacity in the mediastinum . some cysts that lie beneath the carina can not be visualized by chest x - ray . moreover , ct scan and magnetic resonance imaging ( mri ) may both provide accurate diagnosis of bronchogenic cysts using typical characteristics of a round , well - circumscribed , unilocular mass with density of water . more specifically , uniform low t1 and high t2 intensities , indicative of water density , are demonstrated on mri . roughly , half of the cysts have attenuation values of soft - tissue because of viscous mucoid contents making them indistinguishable from neoplasms . although magnetic resonance may help to further differentiate these lesions , they can still be confounded with malignancies presenting with central necrosis . nevertheless , ebus is a new promising modality , which has broadened the diagnostic possibilities for airway and mediastinal pathology . both ultrasound probes ( radial with a balloon-20 mhz and the convex one-7.5 mhz ) in the present case , ebus detected easily the cystic lesion determining further its extent and relation to the airway wall and key anatomic structures and characterizing the intrinsic composition of its content . more specifically , ultrasound image showed a hypoechoic lesion with fine internal echoes within it thus suggesting mainly a viscous fluid - filled cyst . echogenicity of cystic lesions is related to their cellular content and echogenicity is by convention described with reference to soft - tissue such as lymph nodes or tumors . darker ( hypoechoic ) or black ( anechoic ) images denote either cysts with serous fluid or blood vessels . echogenic images within cysts identify complicated fluid collections that may contain either frank pus or blood clots . the presence of septations , thickened walls or floating debris within the cyst may give further radiological clues to an infected cyst . therefore , ebus can be used to diagnose bronchogenic cysts that present as soft - tissue densities on ct imaging . if there is any doubt in the diagnosis , then ebus transbronchial aspiration can be considered and aspirate sent for bacterial cultures and cytological analysis . despite extensive investigations , the nature of a cystic lesion in the thorax can not be ascertained in a significant percentage of individuals preoperatively . differential diagnosis of bronchogenic cyst includes many other entities such as , congenital cysts and malformations ( pericardial cysts , cystic hygroma / lymphangioma , neurenteric cyst , esophageal duplication cyst , thyroid colloid cyst , thymic cyst ) , hydatid cysts , lymphoma , lung abscess , fungal disease , tuberculosis , infected bullas , vascular malformations , mediastinal tumors , hematoma , sarcoidosis , pancreatic pseudocyst ( for retroperitoneal bronchogenic cysts or for pancreatic pseudocysts that extend intrathoracically through the aortic hiatus or esophageal hiatus ) and pulmonary masses ( congenital cystic adenomatoid malformation , pulmonary sequestration , lung cancer , metastases ) . surgical resection remains the mainstay and the only curative treatment for bronchogenic cysts , even though they are asymptomatic and vary in their clinical behavior . the crucial point for avoiding cyst recurrences is the complete excision of the mucosal lining . in addition , convex - probe ebus has an important implication in the management of the bronchogenic cyst as shown by recently published case studies , where it was successfully used to puncture and aspirate the cyst contents in patients who were unfit for surgery . furthermore , real - time ultrasound allows complete aspiration of the cyst that is not always possible when blind techniques are employed . this results in cyst collapse and adhesion of the mucosal lining thus diminishing recurrence rates . this is more likely a temporary procedure when emergency decompression of the cyst is needed to relieve a significant airway narrowing or in patients not fit for thoracotomy or other invasive procedure . the disadvantage of the option is the possible increase in the cyst size later and the minimal risk of malignant transformation . ebus has a potential role in diagnosis , when a confident diagnosis of bronchogenic cyst can not be made by ct . in particular , it can easily identify the cystic lesion and clearly clarify its nature as well as provide imaging guidance for therapeutic procedures .

diagnosis of bronchogenic cysts is possible with computed tomography , where the cysts are seen usually as well - circumscribed lesions of water density . however , many of the cysts have a soft - tissue density thus rendering them indistinguishable from neoplasms . in this article , we describe a case of bronchogenic cyst presenting as soft - tissue mass that was evaluated and diagnosed by endobronchial ultrasound ( ebus ) . we discuss the ultrasound image characteristics of the cyst and its histopathology findings . ebus seems to be a valuable tool in the diagnosis of bronchogenic cysts and also enables their complete aspiration .

bone metastases originating from esophageal cancer are uncommon and occur in about 9% of newly diagnosed patients , and prognosis is poor . generally , treatment for cancer patients with distant metastasis differs from that for patients without distant metastasis . the standard treatment for patients with distant metastasis , such as bone metastasis , is systemic chemotherapy , but the mainstay for patients without distant metastasis is surgical resection . therefore , diagnosis of metastasis is important for treatment planning , especially when it is difficult to diagnose bone metastasis from magnetic resonance imaging ( mri ) and positron emission tomography ( pet ) . spinal bone marrow hyperplasia can mimic bone metastasis on mri and fluorodeoxyglucose ( fdg)-pet , which can affect patient management . there were few reports of bone marrow hyperplasia in a patient with cancer . here , we report a case of esophageal cancer with bone marrow hyperplasia mimicking bone metastasis . a 63-year - old man presented to his primary care physician with numbness in the right hand . paralysis of the ulnar nerve was suspected ; therefore , he underwent cervical spinal mri . mri demonstrated multiple low - intensity areas in his cervical vertebrae , which were suspicious of bone metastases ; thus , he was admitted to our hospital . total spinal mri was performed and demonstrated several low - intensity lesions in the cervical and thoracic vertebrae , sacrum and sternum ( fig 1a , b , f ) . on fat - suppressed t2-weighted images , hyperintense areas were not seen in the cervical and thoracic vertebrae ( fig 1d ) . in contrast - enhanced mri , the low - intensity vertebral lesions lacked contrast ( fig 1c ) . however , on fat - saturated t1-weighted images , the sacral lesion was not seen because the signal was equivalent to that of the adjacent marrow ( fig 1e ) . based on the mri results , the radiologist reported that the low - intensity areas were equivocal as to whether they represented bone metastases . to investigate the origin of the tumor and spread of metastatic - like lesions , fdg - pet / ct was performed . we noted a focal increase in fdg uptake in the intrathoracic esophagus , sternum , and sacrum ( fig 2 ) . the standard uptake values ( suvs ) of the thoracic esophagus , sternum , and sacrum were 4.3 , 2.8 , and 3.0 , respectively . as a result of these findings , we performed upper gastrointestinal endoscopy . a flat , elevated esophageal tumor ( type 0iia+iib ) the length of the tumor was 5 cm , lying on the lower third of the thoracic esophagus and extending to the submucosa . he had been smoking 10 cigarettes daily and had consumed 1.7 l beer daily for 44 years . the laboratory data showed macrocytic anemia ( hemoglobin 10.5 g / dl , mean corpuscular volume 111.5 fl ) and mild liver damage ( glutamic oxaloacetic transaminase 53 ct of the chest and abdomen did not demonstrate thickening of the esophageal wall , lymph node swelling or distant metastasis . a biopsy of the sternum was performed because bone metastasis from early - stage esophageal cancer is unusual and definitive diagnosis of bone metastasis would exclude the patient from surgery . we selected the sternum for biopsy because there were positive findings on both mri and pet / ct , and it was a lesion upon which we could easily perform a biopsy . the biopsy revealed that the low - density area in mri was bone marrow hyperplasia . so , the patient underwent subtotal esophagectomy with three - field lymph node dissection by thoracoscopy and retrosternal anastomosis of the stomach to the cervical esophagus . histologically , the tumor was a moderately differentiated scc at a depth of the submucosal layer , and it had negative surgical margins and positive lymph node metastases [ pn2 ; # 106tbl : left tracheobronchial lymph nodes ( 2/4 ) ] . he has been regularly followed without adjuvant therapy and has remained recurrence - free for 26 months since his operation . this was a rare case emphasizing the importance of distinguishing between bone metastasis and bone marrow hyperplasia in esophageal cancer . the main treatment for esophageal cancer with distant metastasis , including bone metastasis , is systemic chemotherapy but not surgery . meta - analysis demonstrated that fdg - pet and mri were significantly more accurate than ct and bone scintigraphy for the diagnosis of bone metastasis . however , it is difficult to distinguish lesions such as compression fracture of the spine due to osteoporosis and bone marrow hyperplasia from bone metastasis , using several imaging methods . there are very few reports of bone marrow hyperplasia with cancer ; therefore , we have the potential to misdiagnose bone marrow hyperplasia as bone metastases when not diagnosed carefully . bone marrow hyperplasia is a marrow reconversion that refers to repopulating yellow marrow to red marrow . the causes of reconversion are reported to be chronic anemia , treatment with granulocyte - macrophage colony - stimulating factor , and heavy smoking [ 4 , 5 , 6 ] . our case had chronic anemia and heavy smoking as risk factors for bone marrow hyperplasia . typically , bone marrow hyperplasia has similar or lower signal intensity to skeletal muscle on t1- and t2-weighted images and is slightly more hyperintense than muscle on fat - suppressed images . bone metastatic lesions on t1-weighted images showed lower intensity than the skeletal muscle , and those on t2-weighted images showed increased signal intensity . therefore , it was difficult to distinguish between bone metastasis and bone marrow hyperplasia . on fat - suppressed t2-weighted images , these results showed lower signal intensity on t1- and t2-weighted images and higher intensity on the fat - suppressed t2-weighted images . however , bone marrow hyperplasia also showed high uptake compared with adjacent normal - appearing vertebrae . reported a case of a bronchioloalveolar carcinoma with focal nodular bone marrow hyperplasia in dorsal vertebral bodies revealed on fdg - pet and mri . after all , like our case , bone biopsy was necessary for their case for a definitive diagnosis . so , bone marrow hyperplasia often shows similar findings to bone metastasis on fdg - pet and mri . therefore , distinguishing between bone marrow hyperplasia and bone metastasis may be difficult with mri and pet / ct in some cases . their quantitative study showed that mean maximum suv ( suvmax ) for bone marrow hyperplasia was significantly lower than that for bone metastasis , and indicated that quantitative assessment using suvmax > 3.6 is useful for differentiating bone marrow hyperplasia from bone metastasis . in our case , on pet / ct , suvmax of the sternum and sacrum was 2.8 and 3.0 , respectively , both of which were < 3.6 . in contrast , there was no uptake in the vertebrae . these findings may become one way to distinguish between bone metastasis and bone marrow hyperplasia . in addition , his study demonstrated that there was no abnormal uptake in areas involved in bone marrow hyperplasia on bone scintigraphs . therefore , there was a significant difference in the uptake between bone marrow hyperplasia and bone metastasis , and bone scintigraphy can be useful for a differential diagnosis . in conclusion , it is sometimes hard to distinguish between bone marrow hyperplasia and bone metastasis using various imaging methods in cancer patients . because esophageal cancer patients may have some risk factors of bone marrow hyperplasia , if physicians encounter a similar patient to the present case , they should take bone biopsy into consideration for accurate diagnosis . all the procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation ( institutional and national ) and with the helsinki declaration of 1964 and later versions . there are no financial or other relations that could lead to a conflict of interest .

a 63-year - old man visited the clinic with numbness in the right hand . magnetic resonance imaging demonstrated multiple low - intensity lesions in the cervical vertebrae and sacrum , which was suspicious of cervical bone metastasis . fluorodeoxyglucose positron emission tomography / computed tomography revealed areas of increased fluorodeoxyglucose uptake in the thoracic esophagus , sternum and sacrum . a flat , elevated esophageal cancer was identified by upper gastrointestinal endoscopy , and the macroscopic appearance indicated early - stage disease . from the cervical , thoracic and abdominal computed tomography images , there were no metastatic lesions except for the bone lesions . to confirm whether the bone lesions were metastatic , we performed bone biopsy . the histopathological diagnosis was bone marrow hyperplasia . it was crucial for treatment planning to establish whether the lesions were distant metastases . here , we report a case of esophageal cancer with bone marrow hyperplasia mimicking bone metastasis .

even though cases of ovarian cancer do not occur frequently , this disorder does not take the leading position in the structure of cancer pathology . however , it remains to be one of the unsolved problems of the medicine . according to the estimates of the international agency of cancer research there are nearly 239,000 of new cases of ovarian cancer registered annually in the world , and the standard incidence index equals to 6.1 per 100,000 of population ( 1 ) . at the same time , the increasing number of ovarian cancer patients has been increasing in many countries in the last decades . poor prognosis of the disease , despite the advances in diagnosis and treatment , causes a major medical and public health concern ( 24 ) . epidemiological studies of ovarian cancer conducted recently in kazakhstan ( 5 , 6 ) show that the dynamics of incidence indexes are raising , though the component analysis particularly , the one taking into consideration ethnic characteristics , has never been conducted . component analysis of the dynamics of malignant tumors in kazakhstan has been performed generally in all localizations ( 7 ) , with the cancer of the esophagus ( 8) and malignant tumors of the cns ( 9 ) . the study of the dynamics of malignant tumors is essential for planning and management of drug treatment for policy - makers . during this process for example , to what extent the increase in incidence is associated with aging of the population , and to what extent - to an increased risk of developing the disease due to the emergence of new or intensification of existing epidemiological factors . undoubtedly , identification and solution of such problems over the study period in this population are necessary , unless significant changes in registration and the quality of diagnosis could have occurred ( 10 ) . growth of incidence of the ovarian cancer is the result of accumulation of elements of complex combinations of different component structures . investigation of changes in the incidence of ovarian cancer in dynamics represents scientific and practical interest , especially with the component analysis . performance of such analysis for the study of individual components of the change in incidence , influencing its level , will allow oncology service management to identify the factors leading to the occurrence of ovarian cancer , and to organize targeted cancer control . the aim of the study was to perform component analysis of the dynamics of incidence of ovarian cancer of the female population of kazakhstan from 1999 to 2009 taking into account their ethnic background . the major source of the information on the incidence of the ovarian cancer was primary data on registered patients with malignant tumors in the whole country . the data of the committee of statistics of the ministry of national economy of the republic of kazakhstan on the female population was also used as the source of information ( 11 ) . retrospective study ( 19992009 ) incidence rates were calculated according to generally accepted methods of health statistics ( 12 , 13 ) and are represented by 100,000 ( 00000 ) of the corresponding female population . the study was approved by the local ethical committee and administrative permission was obtained from jsc astana medical university . the information may be shared for research purposes only if a requesting organization provides the data security and under takes all the necessary actions in making unable the identity of respondents , in concordance with the principles of the world medical association ( wma ) declaration of helsinki ethical principles for medical research involving human subjects , adopted by the 18th wma general assembly in helsinki , finland , in june 1964 . the dynamics of the ovarian cancer in the female population of kazakhstan was studied based on the guidelines of dvoyrin and axel ( 10 ) . this method of analysis allows segmentation of growth of the number of the diseased belonging to the same population , but at different time . the first three components are related to the changes in population number , age structure of population , and the combined influence of these factors . the fourth component is determined only by the change of the risk index of the malignant ovarian tumor and the other three components are related to the risk associated with the population growth , changes in its age structure and the resulting effect of all three factors . many researchers understand the term a disease risk as the whole complex of reasons that can lead to increase , reduction or stabilization of morbidity indexes . the component method used for analysis of the dynamics of the number of ovarian cancer patients was performed on cases that occurred from 1999 to 2009 among the entire female population , including females of kazakh and russian nationalities , as the studied ethnic groups still take a leading position in both the number of the female population and among the ovarian cancer patients . mathematical calculations for component analysis of morbidity dynamics for malignant tumor ovarian in population of kazakhstan were produced using microsoft excel program and are presented in the relevant tables . the following symbols and abbreviations were used in this article : pij the incidence of ovarian cancer at certain age in the i- th and in the j - th years , nij population size at certain age in the ith to j - th years , pj and nj crude incidence rate and the total population size in the j - th year respectively , j=1 the start year of observation , j=2 the final year of observation , nijnj = sij the proportion of patients aged i in the total population size in the j - th year , asp the age structure of the population , si structural indexes , rp risk of progressing , noc the number of ovarian cancer cases , pn population number , eni the expected number of infected . demographic change of the population is one of the most important epidemiological factors that influence the occurrence of cancers in the population , in particular ovarian cancer in women . thus , the number of total female population of the country over the study period ( 19992009 ) increased from 7 752 100 ( 1999 ) up to 8 185 900 ( 2009 ) , while the number of women of kazakh nationality increased and population of russian women decreased ( fig . 1 ) . change in the size of female population of kazakhstan for 19992009 the age structure of the female population has changed over this period in the individual age groups ( fig . 2 ) . thus , the proportion of women increased in general population for the 5059 age group ( 3.2% ) and 70 years and older ( 0.6% ) years , kazakh women aged 4049 ( + 2.9% ) , 5059 ( + 2.2% ) , 6069 ( + 0.5% ) and in russian women aged 5059 ( + 3.8% ) and 70 years and older ( + 1.4% ) . the change in age structure of the female population ( a total , b kazakh , c russian ) in kazakhstan for 1999 to 2009 ( % ) the results of the component analysis of the dynamics in the number of ovarian cancer patients in all kazakh and russian female population of kazakhstan since 1999 to 2009 is presented in tables 1 and 2 . component analysis of ovarian cancer incidence growth in kazakhstan component analysis of the dynamics of ovarian cancer incidence growth in kazakhstan the analysis of morbidity of the ovarian cancer in dynamics showed the growth of indexes , with the total increase in 2009 compared to 1999 caused by the changes in the age structure of the population , the disease risk and the combined influence of the age structure and the disease risk . at the same time , the growth of indexes among russian female population is mainly caused by the changes associated with risk of infection ( =p=+0.81 + 2.03 respectively ) , and for kazakh females it is mostly caused by changes in the age structure of the population ( =b=+0.91 ) . the internationally recognized epidemiological patterns say that with the population growth and the changes in its age structure the number of patients should grow as well . it can be concluded from the researches that in general the dynamics of the number of patients with ovarian cancer for the entire female population of kazakhstan can be caused by the following factors ( table 3 ) . components of increase in the number of cases of ovarian cancer in kazakhstan growth population number p=+22.1% ( kazakh p=+46.1 , russian p=259.3% ) ; changes in the age structure of the population a=+32.7% ( kazakh a=+15.7% , russian a=+130.8% ) . combined effect of changes in population number and its age structure pa=+1.8% ( kazakh pa=+7.2% , russian pa=19.2% ) . combined effect of changes in the disease risk and population number pr=+2.0% ( kazakh pr=+3.5% , russian pr=36.3% ) . combined effect of changes in the disease risk and age structure of the population ar=+5.1% ( kazakh ar=+3.5% , russian ar=36.3% ) . combined effect of the changes in the disease risk of the population and its age structure par=+0.3% ( kazakh par=+0.6% , russian the total increase in the absolute number of patients overall ( all nationalities ) equals the sum of components : n2n1=+38 + 57 + 3 + 63 + 4 + 9 + 0= = + 174 or + 25.4% in comparison with the primary number of patients ( 174686100=25.4% ) . at the same time , the components of the growth in the percentage at the primary level are equal for the whole female population : + 5.6 + 8.3%+0.5%+14.4%+9.1%+0.5%+1.3%+0.1%=+25.4%+11.0% the overall increase for kazakh female population equals to : n2n1=+62 + 37 + 10 + 18 + 5 + 3 + 1= = + 135 or + 57.9% compared to 1999 ( 135233100=57.9% ) , the components were : + 26.6%+15.7%+4.2%+46.5%+7.6%+2.0%+1.4%+0.4%+11.4%=+57.9% the overall increase for russian female population equals to : n2n1=52 + 264 + 497 + 91= = + 20 or + 5.7% compared to the original number of patients ( 20353100=5.7% ) . according to that , the components of growth in percent of the initial level were equal to : 14.7%+7.4%1.1%8.4%2.1%+14.0%+2.5%0.4%+14.0%=+5.7% thus , ovarian cancer in kazakhstan is characterized by the increase in the number of patients due to the changes in total number and the structure of the population ( for the entire female population + 14.4% of the total growth of + 25.4% ; for kazakh female population + 46.5 of the total growth + 57.9% and for russian female population 8.4% of the total growth of + 5.6% ) . the actual growth of ovarian cancer cases is significant and is equal to + 9.1% for the whole population , + 7.6% for kazakh women and + 14.0% for russian women . the components are grouped into 3 classes , one of which represents different kinds of changes in the population ( p+a+pa ) , the second one shows only the growth of disease risk ( r ) and the third the relationship between these factors ( pr+ar+par ) . therefore , to characterize the cumulative effect of changes in population or the disease risk the components of the 1st and 2nd class the effect of influence of the 3rd class components should be added : ( p+a+pa)+(pr+ar+par)r+(pr+ar+par ) ( p+a+pa)+(pr+ar+par ) if the overall increase in the number of ovarian cancer patients for the female population ( 174 ) is taken as 100% , the increase associated with the disease risk is + 43,4% ( ( + 9.1 + 0.5 + 1.3 + 0.1)25.4100 ) and with pure risk growth it equals to + 36.0% . for kazakh women the growing number of the disease risk ( 135=100% ) will be + 19.7% ( ( + 7.6 + 2.0 + 1.4 + 0.4)57.9100 ) , and with pure increased risk of + 13.1% , respectively , and for russian women ( 20=100% ) the growth of ovarian cancer risk will be 247.7% ( ( + 14.02.1 + 2.50.4)5.6100 ) , and with pure increased risk + 246.8% . various component structures in ovarian cancer at different times or in different groups of the female population at the same time period may provide important information for the construction of epidemiological hypotheses about possible causal role of environmental factors . thus , the number of patients with ovarian cancer in the whole country is increasing . the growth is mainly caused by population growth , the combined effect of changes in population number and its age structure , the changes if infection risks , the combined effect of changes in the infection risks and age structure of the population . the results of the component analysis of the dynamics of ovarian cancer infections in kazakhstan are recommended to use when planning anti - cancer activities of ovarian cancer . the number of patients with ovarian cancer has been steadily increasing in the republic of kazakhstan . it was found that the increase in the number of patients with this malignant disease is caused mainly by the change in the total number and age structure of the population , and their combined action , as well as the increase of risk of developing the disease due to the emergence of new or intensification of existing epidemiological risk factors . the results of the component analysis of the dynamics of ovarian cancer cases in kazakhstan are recommended to use when planning anti - cancer activities of ovarian cancer . ethical issues ( including plagiarism , informed consent , misconduct , data fabrication and/or falsification , double publication and/or submission , redundancy , etc . ) have been completely observed by the authors .

background : we examined epidemiological aspects of dynamic changes in incidence of ovarian cancer in women of kazakh and russian nationalities in kazakhstan.methods:the material of investigation was primary data on registered patients with malignant ovarian tumors in the whole country . the study was conducted during the period of 19992009 . evaluation of changes in ovarian cancer incidence in the female population of kazakhstan was performed using component analysis.results:the number of patients with ovarian cancer in the whole country is increasing . this increase is due to several major reasons , including population growth ( all females p=+22.1% , females of kazakh nationality p=+46.0% and females of russian nationality p=259.3% ) , changes in the age structure ( all females a=+32.7% , females of kazakh nationality a=+27.1 and females of russian nationality a=+130.8 ) , and changes in risks of developing the disease ( all females r=+36.0% , females of kazakh nationality r=+13.1% and females of russian nationality r=+246.8%).conclusion : this investigation was the first epidemiological study of dynamics of ovarian cancer by component analysis in women of kazakh and russian nationalities in kazakhstan . implementation of the results of the study is recommended in management of anti - cancer activities for ovarian cancer .

anthocyanins , as ubiquitous constituents of berries and coloured vegetables , are widespread in the plant dominion . much attention has been paid in recent years to their radicals scavenging activity in vitro and in vivo and possible health benefits . the main anthocyanins being analysed in elderberries are various glucosylated cyanidins ( figure 1 ) . besides glucose , sambubiose is the typical sugar conjugate in elderberries [ 1 , 2 ] . rate and extent of absorption , metabolisation , and excretion of elderberry anthocyanins are to date not fully understood . first of all , controversially discussed hitherto is whether also conjugated glucuronides of cyanidin are formed and excreted in vivo . time - course plots ( mean sd ) of total anthocyanins ( glucosides + glucuronides ) and anthocyanin glucuronides in human urine following ingestion of 150 ml of elderberry juice . individual amounts excreted of total anthocyanins ( glucosides + glucuronides ) and anthocyanin glucuronides within 5 hours following ingestion of 150 ml of elderberry juice . urinary excretion of anthocyanins as unchanged glucosides and glucuronides after elderberry juice consumption ( means sd ) . calculated as the ratio of amounts excreted ( within 5 h ) to amounts / doses ingested . the study protocol was approved by the ethics committee of the giessen university , germany . after an overnight fasting , seven healthy nonsmoking volunteers ( 6 female and 1 male with a mean bmi of 21.5 ) consumed a bolus quantity of 150 ml of concentrated elderberry juice ( containing 3.57 g of total anthocyanins ) together with rolls and cheese . the elderberry juice concentrate was obtained from wild ( heidelberg , germany ) . urine samples were collected initially and in hourly intervals over a period of 5 hours . hplc - dad analyses of urinary samples ( 05 hours after ingestion ) were performed before and after hydrolysis of glucuronide conjugates with -glucuronidase [ 3 , 4 , 5 , 6 ] . the anthocyanins were extracted by using a solid phase extraction cartridge ( sep - pakvac 12 , waters , milford , mass ) . the cartridge was first washed with 5 ml methanol and equilibrated with the same volume of 5% aqueous formic acid . seven ml urine samples diluted with 2 ml formic acid were applied to the equilibrated cartridge . after washing with 5 ml of 5% formic acid , the anthocyanins were eluted with 5% formic acid in 5 ml methanol . the eluate was evaporated to dryness in a vacuum rotary evaporator at 30c and the extract redissolved with 200 l mobile phase before hplc analysis . the chromatographic conditions adopted from netzel et al comprised separation on a prontosil eurobond rp-18 ( 5 m , 250 4 mm i d , bischoff , leonberg , germany ) , protected by a guard column ( lichrospher 100 rp-18 , 4 4 mm , merck , germany ) , and isocratic elution with water / formic acid / acetonitril ( v / v / v ) = 81/10/9 ( flow rate 0.5 ml / min ) by using a high - precision pump ( model l-6200 , merck - hitachi , darmstadt , germany ) . the cyanidin glucosides were detected at 520 nm with the aid of a uv - vis detector ( l-4200 , merck - hitachi ) . cyanidin glucosides excreted were identified by spiking blank urine samples with authentic compounds and comparing the retention time in the hplc analysis and uv - visible spectra . standard curves were prepared for quantification prior to the preparation procedure . the detection limit ( s / n 10 ) was between 0.13 ng and 0.60 ng / injection volume ( 100 l ) . aliquots of each urine sample were acidified with formic acid ( 2 ml/0.2 ml ) and stored frozen at 80c until analysis . the urinary excretion of total anthocyanins ( unchanged cyanidin glucosides and their glucuronide conjugates ) within 5 hours was 0.053 0.030% of the administered dose . only 6.2 2.2% of the excreted amount consisted of glucuronides . based on this recovery , the percentage of glucuronides in urinary excretion was 0.003 0.001% ( calculated as the ratio of anthocyanin glucuronides excreted to anthocyanin glucosides ingested ) . the excretion pattern of total anthocyanins in figure 2 demonstrates that a maximal excretion rate is reached 1 hour after intake , followed by a rapid drop to initial values about 5 hours after intake , resembling a first - order excretion kinetics . the metabolic conversion of anthocyanins within the organism remains to be elucidated . in principle , glucuronidation or conjugation with sulphuric acid is a common final metabolic step to facilitate urinary excretion . tsuda et al found no cyanidin glucuronides in livers and kidneys of rats after oral administration of cyanidin 3-glycoside , but cyanidin was converted to peonidin and protocatechuic acid . a different situation seems to exist to date in man . in the urinary excretion of elderly women , minor amounts of glucuronides of peonidin and cyanidin 3-glucoside could be deteced in half of the volunteers besides unchanged glucosides after elderberry consumption , which does correspond to our results [ 2 , 5 ] . only glucosides of elderberry anthocyanins , however , could be found in plasma and urine of volunteers by other authors [ 8 , 9 ] . to entirely estimate the extent of glucuronidation of anthocyanins as metabolic fate , it has to be considered that besides urinary excretion , biliary secretion may also serve as a possible way of elimination , particularly known for glucuronides . newer studies , however , revealed that after intake of elderberry extract , the identical pattern of glucosylated cyanidins could be detected in plasma as in urine . thus , the results of the quantification of excretion products in the present study demonstrate that , at least in the given dose range , glucuronidation of cyanidin obviously represents a negligible conversion step in the metabolism of cyanidin ingested from elderberries . the proportion of glucuronide conjugates seems to represent a rather constant but very small proportion despite interindividual differences of total anthocyanin excretion ( figure 3 ) . this may be in contrast to other fruits such as strawberry anthocyanins , being predominantly excreted in urine as glucuronides besides small amounts of sulfoconjugates . it remains to show the extent to which the administered dose level does determine the site of metabolism . there exists some body of evidence that large doses of polyphenols are primarily metabolised in the liver , whereas small doses may be metabolised by the intestinal mucosa , with the liver playing a secondary role to further modify the polyphenol conjugates .

in a pilot study with 6 females and 1 male , the metabolism of various cyanidin glucosides after oral administration of elderberry juice was investigated . the anthocyanin metabolites were detected in urinary excretion . after ingestion of a bolus quantity of 3.57 g total anthocyanins in a 150 ml elderberry juice concentrate , 0.053% of the administered dose was excreted in urine as glucosidically bound cyanidins within the first 5 hours . only 0.003% of the ingested anthocyanin glucosides was excreted as cyanidin glucuronide , suggesting that this conversion step might be of minor importance in urinary excretion .

osteoarthritis ( oa ) is a degenerative joint disease of multifactorial origin.1 estimated population prevalence varies from 430% depending on the age , sex and disease definition.2 risk factor include obesity , previous knee injury , selected physical activities , the presence of hand oa ( heberden s nodes ) and the family history of the disease.3,4 of all the risk factors known , obesity is most strongly associated with development and progression5 - 9 of koa . two major theories have been proposed to explain this association : biomechanical and systemic / metabolic mechanisms10.the biomechanical theory suggests that obesity increases axial loading ( local effect ) with consequent degeneration of articular cartilage , whereas metabolic theory proposes that some metabolic factors adversely affect cartilage and obesity acts indirectly to increase the risk of koa.11 anthropometry is the study of the measurement of the human body in terms of the dimension of bone , muscle and adipose tissue . literature shows that muscle mass or muscle strength is protective for the development of osteoarthritis.12 - 14 because bmi is a measure of both fat and lean mass , the relative contribution of adipose tissue and muscle mass , and their contribution to muscle strength can not be disaggregated.15 anthropometric measurements such as bmi , skin fold thickness and mid upper arm circumferences will allow cross sectional analysis of the relationship between obesity and risk of disease . the purpose of the present study was to examine the validity of the contention that bmi and other anthropometric measures have a significant relationship with the severity of osteoarthritis knee in nonobese subjects . six hundred sixty seven individuals attending orthopaedic opd with knee pain underwent a physician lead clinical and radiological examination to verify their eligibility for inclusion as per guidelines of american college of rheumatology ( acr)16 . individuals with any evidence of secondary oa , inflammatory arthritis and those with neurological conditions were excluded . 180 cases of primary osteoarthritis knee ( koa ) could be enrolled for the study . the voluntary written consent was taken from all the subjects for participation in the study . all the radiographs were evaluated by at least two readers with a third consensus reader for the presence of koa defined by the kellgrenlawrence ( kl ) grade.17 oa was defined as the presence of at least one knee with a grade 2 or higher . joint space width of tibial medial compartment ( tmc ) and tibial lateral compartment ( tlc ) were measured18 in mms and tibiofemoral alignment was measured19 as either > 180 or < 180 depending on valgus or varus malalignent . clinical assessment was done by visual analogue scale ( vas ) for knee pain and western ontario mcmaster universities osteoarthritis ( womac)20 index for knee pain and knee related disability . the patients were weighed with a calibrated balance beam scale to the nearest 0.1 kg in possible minimum clothing and standing height was measured with stadiometer in centimeters ( cms ) . mid upper arm circumference , triceps skin fold thickness and waist hip ratio was measured by standard procedure at standard location.21 physical activity scores were calculated by framingham physical activity index.28 the descriptive statistics of the subjects were calculated ( meansd ) . the one way analysis of variance ( anova ) was used to estimate the significant difference between / among various anthropometric measures and severity of osteoarthritis knee in terms of kl grades and lsd pairwise test was applied in case of any variable found to be significant in anova . difference of mean values of anthropometric measurements was analyzed by nonpaired ttest between dichotomous variables of kl grade , whereas pearson product correlation was used for continuous variable of kl grades and anthropometric measures . six hundred sixty seven individuals attending orthopaedic opd with knee pain underwent a physician lead clinical and radiological examination to verify their eligibility for inclusion as per guidelines of american college of rheumatology ( acr)16 . individuals with any evidence of secondary oa , inflammatory arthritis and those with neurological conditions were excluded . 180 cases of primary osteoarthritis knee ( koa ) could be enrolled for the study . the voluntary written consent was taken from all the subjects for participation in the study . all the radiographs were evaluated by at least two readers with a third consensus reader for the presence of koa defined by the kellgrenlawrence ( kl ) grade.17 oa was defined as the presence of at least one knee with a grade 2 or higher . joint space width of tibial medial compartment ( tmc ) and tibial lateral compartment ( tlc ) were measured18 in mms and tibiofemoral alignment was measured19 as either > 180 or < 180 depending on valgus or varus malalignent . clinical assessment was done by visual analogue scale ( vas ) for knee pain and western all the radiographs were evaluated by at least two readers with a third consensus reader for the presence of koa defined by the kellgrenlawrence ( kl ) grade.17 oa was defined as the presence of at least one knee with a grade 2 or higher . joint space width of tibial medial compartment ( tmc ) and tibial lateral compartment ( tlc ) were measured18 in mms and tibiofemoral alignment was measured19 as either > 180 or < 180 depending on valgus or varus malalignent . clinical assessment was done by visual analogue scale ( vas ) for knee pain and western ontario mcmaster universities osteoarthritis ( womac)20 index for knee pain and knee related disability . the patients were weighed with a calibrated balance beam scale to the nearest 0.1 kg in possible minimum clothing and standing height was measured with stadiometer in centimeters ( cms ) . mid upper arm circumference , triceps skin fold thickness and waist hip ratio was measured by standard procedure at standard location.21 physical activity scores were calculated by framingham physical activity index.28 the patients were weighed with a calibrated balance beam scale to the nearest 0.1 kg in possible minimum clothing and standing height was measured with stadiometer in centimeters ( cms ) . mid upper arm circumference , triceps skin fold thickness and waist hip ratio was measured by standard procedure at standard location.21 physical activity scores were calculated by framingham physical activity index.28 the descriptive statistics of the subjects were calculated ( meansd ) . the one way analysis of variance ( anova ) was used to estimate the significant difference between / among various anthropometric measures and severity of osteoarthritis knee in terms of kl grades and lsd pairwise test was applied in case of any variable found to be significant in anova . difference of mean values of anthropometric measurements was analyzed by nonpaired ttest between dichotomous variables of kl grade , whereas pearson product correlation was used for continuous variable of kl grades and anthropometric measures . the age of the subjects varied from 40 to 72 years ( mean 54.11 years ) . out of total number of 180 subjects , 99 ( 55% ) were overweight with male female ratio being 28:71 and 81 ( 45% ) were normal in a ratio of 29:52 . 9 males and 13 females were in kl grade 2 , 32 males and 71 females in kl grade 3 and 16 males and 39 females in kl grade 4 . physical activity scores were significantly associated , as kl grade 2 had higher score ( 33.91 4.20 , 32.883.50 ) in comparison to kl grade 3 ( 33.404.71 , 31.562.80 ) and 4 ( 31.314.90 , 30.593.10 ) in males and females respectively ( table 1 ) . in both the genders bmi was not significantly different amongst 3 kl grades studied together , however pairwise comparison showed that difference was significant between kl grade 2 and 4 in males and in females ( p = 0.048 , p = 0.046 ) . tsft , in males was significantly higher in kl grade 4 ( 13.951.36 ) in comparison to kl grade 3 ( 12.831.90 ) and kl grade 2 ( 12.222.11 ) . whr , in females was marginally significant amongst all 3 grades , however pairwise comparison showed a significant higher whr in kl grade 4 ( 0.860.10 ) in comparison to kl grade 2 ( 0.820.09 ) ( table 1 ) . similarly , clinical evaluation of disease severity by vas and womac index were correlated with anthropometric measures ( table 2 ) . no significant difference was found between anthropometric measures and osteophytes in either compartment in both the gender . in tibiofemoral malalignment ( varus ) = 0.04 ) in males and higher whr ( 0.840.09 , 0.810.09 , p = 0.04 ) in females . joint space width ( jsw ) of tlc was not correlated with any of the anthropometric measures in either gender . however , jsw of tmc in males was significantly negatively correlated with two anthropometric measures bmi ( r = 0.32 , p = 0.01 ) and tsft ( r = 0.37 , p = 0.01 ) . in females , significant decrease of tmc was defined by whr ( r = 0.21 , p = 0.02 ) and tsft ( r = 0.17 , p = 0.04 ) . womac scores were positively correlated with bmi both in males ( r = 0.23 , p = 0.04 ) and in females ( r = 0.24 , p = 0.01 ) . additionally it was also defined by whr ( r = 0.25 , p = 0.01 ) in females ( table 2 ) . the purpose of the present study was to examine the validity of the contention that bmi and other anthropometric measurements have a significant relationship with osteoarthritis knee in nonobese subjects . non obese subjects were taken for study to negate the systemic and metabolic effects of obesity . several studies have shown that body weight rather than body fat distribution is independently associated with koa22,23 davis ma suggests that body fat distribution also play a significant role in koa.22 lauren m abbathe23 found that body composition measurements from dxa and fat distribution by mri were not strongly associated with koa and concluded that such measurements offer no advantage over the simpler measures of bmi or weight in assessment of koa . after extensive literature search we focused our study on the anthropometric measures which were simple to document and have evidence for their role in obesity bmi is a heuristic measure of body weight based on a person 's weight and height . though it does not actually measure the percentage of body fat , it is used to estimate a healthy body weight based on a person 's height . muac is a major determinant of arm muscle and subcutaneous fat , tsft determine peripheral fat distribution and whr central fat distribution . on analysis of the effects of anthropometric measures on koa , in all the subjects taken together , however when data was bifurcated according to genders , bmi and tsft were associated with disease in males and the association was stronger for tsft . in females bmi and whr were significant and whr was more strongly associated . on analysis of individual radiological features , joint space width of tmc in relation to bmi and tsft was found negatively correlated as in previous studies18 , but when data was divided gender wise , in males decrease of tmc was defined by bmi and tsft , however in females decrease of tmc was defined by whr and tsft . david t felson8 postulated that the risk of progression of koa increased significantly with an increase in weight . however this progression was not present in all , but limited to knees from limbs that were moderately malaligned . in neutrally aligned limbs on one end of the spectrum and severely malaligned limbs on the other had no effect on risk of koa progression . leena sharma24 et al found a relationship between bmi and radiographic koa with varus deformity but not in those with valgus knee . the authors were unable to account whether the association precedes or follows the onset of disease . this dilemma has persisted for too long and has been reported by others also . in this study , when all subjects taken together were divided according to tibiofemoral alignment ( varus / valgus ) , as expected we found bmi was associated with varus . however , when data was bifurcated according to genders , the association of bmi and varus was found only in males and in females it was associated with whr . osteophytosis is the first and the cardinal feature in diagnosis of koa , but we found that inspite of high prevalence bmi and all other anthropometric measures were inconsistently associated with osteophyte formation . these results provide direct evidence that increasing weight ( bmi ) may not induce osteophyte formation . in relation to association of knee pain and anthropometric measures our findings were consistent with those of jinks c25 , rogers mw26 and marks r.27 on gender based analysis , whr also emerged a significant factor in females . measurement error may influence results , however , a positive interrelation of anthropometric measures and high reproducibility of radiological measures suggest that this is unlikely . secondly this study was cross sectional in design and can not comment on causal directions , thus longitudinal data will be required to confirm these results . finally there may be confounding factors for which our analysis has been unable to account . such influences might include for example the use of medication , occupation , physical activities and other health problems like cardio vascular disease . this is a true representation of koa of idiopathic variety and finding a significant association is meaningful and a justifiable evidence . this study validates the contention that bmi and other anthropometric measures have a significant association with koa . contrary to common belief , peripheral fat in males and central fat in females were more strongly associated with koa in comparison to heuristic body weight . sources of funding : the study was supported financially by council of science and technology , up , govt . of uttar pradesh , lucknow , india

objective : body mass index ( bmi ) and knee osteoarthritis have a strong association , but other anthropometric measures lack such associations . to date , no study has evaluated nonobese knee osteoarthritis to negate the systemic and metabolic effects of obesity . this study examines the validity of the contention that bmi and other anthropometric measures have a significant relationship with knee osteoarthritis.methods:in total , 180 subjects with a diagnosis of knee osteoarthritis were recruited and classified according to kellgrenlawrence ( kl ) grades . body mass index , midupper arm circumference , waisthip ratio and tricepsskinfold thickness were recorded by standard procedures . osteoarthritis outcome scores ( womac ) were evaluated.results:(1 ) in both genders , the bmi was significantly higher for kl grade 4 than for grade 2 ; tricepsskinfold thickness was positively correlated with the joint space width of the tibial medial compartment . ( 2 ) in males , tricepsskinfold thickness significantly increased as the kl grades moved from 2 to 4 ; the significantly higher bmi found in varus aligned knees was positively correlated with womac scores . ( 3 ) in females , the waisthip ratio was significantly higher for kl grade 4 than for grade 2 ; a significant correlation was found between bmi and womac scores . the waisthip ratio was significantly associated with varus aligned knees and it positively correlated with womac scores and with the joint space width of the tibial medial compartment . the midupper arm circumference demonstrated no correlation with knee osteoarthritis.conclusion:this study validates the contention that bmi and other anthropometric measures have a significant association with knee osteoarthritis . contrary to common belief , the tricepsskinfold thickness ( peripheral fat ) in males and the waisthip ratio ( central fat ) in females were more strongly associated with knee osteoarthritis than bmi .

chest wall skeletal defects are usually closed using muscle flaps , other autogenous tissue , or prosthetic materials . however , reconstruction procedures involving typical muscle flaps , such as the pectoralis major , latissimus dorsi , serratus anterior , and rectus abdominis , need additional incisions and plastic surgery support . further , postoperative complications after prosthetic reconstruction reportedly occur in 46.2% of cases , with infection being a critical complication that occurs in 4.6% of cases , necessitating emergency surgery . no further reconstruction may be needed after healing from the initial surgery has occurred and the infected prosthetic material has been removed , since the lung may be adherent to the chest wall . however , in most cases , additional autogenous tissue flaps are needed . here , we report the use of a subscapular muscle flap to cover posterior chest wall defect after removal of infected prosthetic material . our technique is simple , safe , and can be performed in the same surgical field as the initial surgery , without the need for plastic surgery support . he underwent a right upper lobectomy with posterior chest wall resection , from the third to sixth ribs , via posterior lateral thoracotomy . the chest wall defect was covered with a 17 22 cm polytetrafluoroethylene mesh . the wound created during the initial surgery was incised , the infected mesh was removed , and the thoracic cavity was washed using a large quantity of saline . the subscapularis muscle , the nearest muscle to the defect area , was used to cover the chest wall defect . the scapular tip of the subscapularis muscle was lifted and its lower half was dissected using electric cautery . the same parts of the infraspinatus and teres major muscles were also dissected from the scapula . the free end of the flap was sutured to the stumps of the anterior serratus and rhomboid major muscles , which had been cut during the initial surgery ( fig . the functionality of the upper extremity on the affected side was limited , but was restored with rehabilitation . although scapular and parascapular flaps are commonly used as free flaps in head and neck reconstructions , to our knowledge , no previous study has reported the use of a subscapularis muscle flap for chest wall reconstruction . the main advantage of this flap is that since dissection of the subscapularis muscle is simple , plastic surgery support is not required . thoracic surgeons can preoperatively evaluate the muscle volume using computed tomography and obtain an adequate flap size . in our experience , it is important to suture the subscapularis muscle flap to the serratus anterior and rhomboid major muscles for thoracic cavity closure and to ensure adequate blood supply to the free end of the flap . the subscapularis muscle and scapula are supplied by the dorsal scapular artery , suprascapular artery , and subscapular artery , which form an arterial plexus around the scapula . a previous study identified the angular branch of the thoracodorsal artery to be the main vascular supply to the scapula tip . in the present case , the lower third of the scapula was excised since blood supply to the scapula tip may be reduced after dissection of the subscapularis muscle , and to prevent the scapula tip from falling into the thoracic cavity ( fig . the subscapularis muscle flap surgery for reconstruction of chest wall skeletal defect , following removal of contaminated prosthetic material , is a simple and safe technique that can be conducted in the same surgical field as the initial reconstruction surgery and does not require plastic surgery support . thus , this technique may be an option for posterior chest wall skeletal defect reconstruction . written informed consent was obtained from this patient for publication of this case report and any accompanying figures .

highlightswe performed a subscapular muscle flap surgery to cover a chest wall defect.no previous study has reported this technique for chest wall reconstruction.the subscapular muscle flap technique can be conducted using the same incision as a lobectomy.the subscapular muscle flap technique does not require plastic surgery support.during the technique , the lower third of the scapula needs to be excised .

a good number of drugs and chemicals consumed by pregnant women today have been found to be teratogenic ( i.e. having the ability to induce congenital anomalies).1 drugs such as thalidomide and phenytoin ( to mention few ) have been shown to have this ability , among other chemical agents . the mechanisms surrounding these congenital anomalies are enclosed in a study referred to as teratology . the type and degree of defects produced by these agents depends on the dosage of the agents ingested and the stage of embryonic development of body structures at the time of exposure . such teratogens mainly induce defects during the most critical embryonic period of development ( period of organogenesis ) that is between the 3 and 8 weeks of development in man and 6 to 14 days in wistar rats.2 these teratogens can induce defects by crossing the placenta to disrupt the developmental patterns of the embryo directly or by altering the physiology of the pregnant animal such that this alteration consequently leads to developmental defects in the conceptus.2 plants have been the source of medicines for thousands of years,3 datura metel is a medicinal plant whose use dates back as far as 3000 years.4 today , it is mainly used in traditional chinese medicine as a treatment for asthma , chronic bronchitis , chronic pain , seizures , and coma.4 d. metel has also been used for its anaesthetic , or pain - killing , properties.5 it is known as an anticholinergic , that is , it reduces spasms by blocking the transmission of nerve impulses . in addition , d. metel is a well - known plant with delirium properties;is capable of causing hallucinations . in vietnam d. metel is added to asthmatic cigarettes.4 great care must be taken when using this herb , as the toxic dose is very close to the medicinal dose . twenty adult wistar rats comprising of 12 females and 8 males were used for this study . all experimental investigations were done in compliance with humane animal care standard outlined in the guide to the care and use of animals in research and teaching , as approved by the institute of laboratory animal resource . national resource council . it was identified by the local people and was authenticated at the plant biology department , university of ilorin . the leaf was plucked from the stem , and weighed ( weight was 590 g ) . the solution was left for 24 h and then sieve ; the filtrate was then evaporated to dryness in an oven at 60c . the pregnant rats were administered ethanolic extract of d. metel with the aid of orogastric tube the female rats were divided into four groups ( a_d ) with each group comprising of 3 females . vaginal smear was done every day to determine the proestrous stage of the rats using the method of marcondes et al . , 2002 . once in proestrous , the female rats are introduced to male for mating for 24 hours . the next day , vaginal smear was done to confirm mating ; this was evidenced by the presence of sperm cells in the vaginal smear in the form of a tiny threadlike structure under microscope using 10x magnification . group a : treated group with 500 mg / kg body weight of d. metel extract from the first day of fertilization to parturition . group b : treated group with 500 mg / kg body weight of d. metel extract from the 8 day of fertilization to parturition . group c : treated group with 500 mg / kg body weight of d. metel extract from the 15 day of fertilization to parturition . group d : control group were given 1ml of normal saline throughout the gestation period the weights of the pregnant rats were taken on the first day of fertilization , 8 day after fertilization , 15 day after fertilization and the day of parturition . the gestation period in female rats is normally about 21 - 23 days , although these can vary.7 the rats were allowed to give birth ; the mothers and litters were transferred to the weaning cage . after 21 days of gestation period , the pregnant rats in the control group ( group d ) littered 6 pups averagely ; those treated 14 days after fertilization ( group c ) littered 6 pups averagely ; those treated 7 days after fertilization ( group b ) had abortion ( evidenced by vaginal bleeding on gestational day 14 and 15 ) . those treated from the first day of fertilization ( group a ) showed no signs of pregnancy . administration of extract was stopped for group c after delivery , for group b after noticing the abortion and for group a after 25 days . two litters in each group were sacrificed on the day of parturition ( day 0 ) and 14 days after parturition . after sacrifice the brain was harvested and fixed in 10% formocalcium as promptly as possible ; this procedure was subsequently carried out on other days of sacrifice . the brains are fixed in 10% formocalcium , hippocampus was excised and processed for haematoxylin and eosin ( h & e ) staining.89 the tissues were embedded in paraffin and processed for routine histological studies . the sections were mounted and examined with the light microscope and the photomicrography of each slide was recorded . from the first day of fertilization all rats in both the treated and the control group showed the same weight . graphical representation of the weight changes in the pregnant rats during gestation period on day 7 after fertilization , groups b and c showed the highest increase in weight , followed by groups d and a being the lowest . on day 14 after fertilization , group c showed the highest increase in the level of weight changes followed by groups d , b and a being the lowest . on day 21 after fertilization , group c showed the highest level of weight changes , followed by groups d , b and a being the lowest . group a did not give birth after 25 days group b had abortion after 7 days after administration of ethanolic extract of d. metel leaf . rats in group d gave birth to 6 litters averagely . showing the number of litters given birth per group table 2 shows that litters of rats in group c weighed more than that in group d weight changes ( g ) in litters ( expressed as meansem ) from the photomicrographs , the following can be observed : at day 0 [ figure 2 ] , the hippocampus is not fully developed , but using the third ventricle as a landmark , the lumen of the third ventricle varies with litters of group c showing large lumen as compared to that of litters of the control group . ( l lumen ) . a litters of rats given 500 mg / kg body weight of d. metel during the third week of pregnancy till parturition , b litters of rats given normal saline throughout gestation period at day 14 [ figure 3 ] , the pyramidal cell layer of litters in group c appears dense as compared to that in the control group which shows normal cell density . a litters of rats given 500 mg / kg body weight of d. metel during the third week of pregnancy till parturition , b litters of rats that were given normal saline throughout gestation period . the granular cell layer of the litters in group c shows more vacuoles as compared to litters of group d , more astrocytes is also seen in the litters of group c than that of group d in the granular cell layer . from the first day of fertilization all rats in both the treated and the control group showed the same weight . graphical representation of the weight changes in the pregnant rats during gestation period on day 7 after fertilization , groups b and c showed the highest increase in weight , followed by groups d and a being the lowest . on day 14 after fertilization , group c showed the highest increase in the level of weight changes followed by groups d , b and a being the lowest . on day 21 after fertilization , group c showed the highest level of weight changes , followed by groups d , b and a being the lowest . group a did not give birth after 25 days group b had abortion after 7 days after administration of ethanolic extract of d. metel leaf . rats in group d gave birth to 6 litters averagely . showing the number of litters given birth per group table 2 shows that litters of rats in group c weighed more than that in group d weight changes ( g ) in litters ( expressed as meansem ) from the photomicrographs , the following can be observed : at day 0 [ figure 2 ] , the hippocampus is not fully developed , but using the third ventricle as a landmark , the lumen of the third ventricle varies with litters of group c showing large lumen as compared to that of litters of the control group . a litters of rats given 500 mg / kg body weight of d. metel during the third week of pregnancy till parturition , b litters of rats given normal saline throughout gestation period at day 14 [ figure 3 ] , the pyramidal cell layer of litters in group c appears dense as compared to that in the control group which shows normal cell density . a litters of rats given 500 mg / kg body weight of d. metel during the third week of pregnancy till parturition , b litters of rats that were given normal saline throughout gestation period . the granular cell layer of the litters in group c shows more vacuoles as compared to litters of group d , more astrocytes is also seen in the litters of group c than that of group d in the granular cell layer . the hippocampus , like the rest of nervous tissue , is made up of neurones and neuroglia.10 the neurons are the excitable functional units of the nervous tissue . in this study , rats in group a treated with 500 mg / kg body weight from the day of fertilization to parturition did not show any signs of pregnancy ; this may be because of the failure of the fertilized eggs to implant , which may be as a result of the toxic effect of the extract administered . rats in group b treated with 500 mg / kg body weight for the last 2 weeks of gestation period ( 8 - 21 days of gestation ) , had abortion after 7 days of administration ( day 15 of gestation ) . this proves that the extract is harmful at the critical period of development in rats , which is between the 6 and 13 day of gestation.2 rats in group c treated with 500 mg / kg body weight for the last week of gestation period ( 15 - 21 day of gestation ) gave birth to an average of 6 litters , with no gross and morphological changes when compared to those of the control group . rats in group d treated with normal saline throughout the gestation period ( control group ) gave birth to an average of 6 litters with normal morphological appearance . average weight of litters ingroup c is slightly higher than that of the control group at birth and at day 14 which is approximately 0.5 g [ table 2 ] . histologically at day 0 , the hippocampus of both the litters in group c and group d were not yet fully differentiated from the rest of the limbic system , hippocampus forming the peripheral border of the third ventricle.11 the lumen of the third ventricle was larger in the histological observation of group c as compared to that in group d [ figure 2 ] , which suggests retarded hippocampal development in the foetus of the animal treated with 500 mg / kg body weight of the extract in the last week of gestation . this may be due to the adverse effect of the extract on the neuronal development of the hippocampus . this can be as a result of retarded cell proliferation and differentiation in this part of the brain . it was observed histologically that , at day 14 , the pyramidal cell layer of litters of group c appear dense as compared to the control group that showed normal density [ figure 3 ] . this can be due to late development of the pyramidal cells which may be due to the effects of the extract . the granular cell layer of group c shows more vacuoles compared to the control group and there is presence of more glia in the granular cell layer of group c compared to group d [ figure 3 ] . this vacuolations and more glia may be due to neural cell death and gliosis in the area , which may be caused by the extract.8 in conclusion , it can be deduced that the ethanolic extract of d. metel leaves can be used as a contraceptive because there is no signs of pregnancy in rats that were given 500 mg / kg body weight from the day of fertilization to parturition . it can also be used as an abortive drug when used in early period of gestation as it caused abortion in rats that were given 500 mg / kg body weight for the last 2 weeks of gestation period ( 8 - 21 day of gestation ) . it should be avoided in the late period of gestation , as , seen in the histological observation of tissues of litters in group c , there was retarded hippocampal development , neuronal damage and neural cell death that will affect the normal functioning of the hippocampus .

background : datura metel contains atropine alkaloids and has been used to treat complication like asthma and , bronchitis , because of its anticholinergic properties.aim:this study aimed to determine the prenatal effects of ethanolic extract of d. metel leaves exposure on the development of hippocampus.materials and methods : twenty rats ( 12 females and 8 males ) were purchased . the females were grouped into four groups ( a_d ) . group a were given 500 mg / kg body weight of the extract on the first day of fertilization to the end of gestation period , group b were given 500 mg / kg body weight on the 8th day of fertilization to the end of gestation period , group c were given 500 mg / kg body weight on 15th day of fertilization to the end of gestation period and group d were given normal saline throughout the gestation period.results:rats in group a showed no implantation , rats in group b had abortion on the 7th day after administration , and rats in group c gave birth with their litters showing retarded hippocampus development and neural degeneration and rats in group d ( control ) showed normal development.conclusion:ethanolic extract of d. metel leaf is teratogenic in the late stage of pregnancy , is abortificient and can serve as a contraceptive .