Acute cholecystitis with massive upper gastrointestinal bleed: A case report and review of the literature

BACKGROUND: Cystic artery pseudoaneurysm is a rare complication following cholecystitis. Its presentation with upper gastrointestinal hemorrhage (UGIH) is even rarer. Thirteen patients with cystic artery pseudoaneurysm have been reported in the literature but only 2 of them presented with UGIH alone. CASE PRESENTATION: We report a 43-year-old woman who developed a cystic artery pseudoaneurysm following an episode of acute cholecystitis. She presented with haematemesis and melaena associated with postural symptoms. Upper gastrointestinal endoscopy revealed a duodenal ulcer with adherent clots in the first part of the duodenum. Ultrasonography detected gallstones and a pseudoaneurysm at the porta hepatis. Selective hepatic angiography showed two small pseudoaneurysms in relation to the cystic artery, which were selectively embolized. However, the patient developed abdominal signs suggestive of gangrene of the gall bladder and underwent an emergency laparotomy. Cholecystectomy with common bile duct exploration along with repair of the duodenal rent, and pyloric exclusion and gastrojejunostomy was done. CONCLUSION: This case illustrates the occurrence of a rare complication (pseudoaneurysm) following cholecystitis with an unusual presentation (UGIH). Cholecystectomy, ligation of the pseudoaneurysm and repair of the intestinal communication is an effective modality of treatment

Elevated reticulocyte count – a clue to the diagnosis of haemolytic-uraemic syndrome (HUS) associated with gemcitabine therapy for metastatic duodenal papillary carcinoma: a case report

In adults, the haemolytic-uraemic syndrome (HUS) is associated with probable causative factors in the minority of all cases. Cytotoxic drugs are one of these potential causative agents. Although metastatic cancer by itself is a recognized risk-factor for the development of HUS, therapy with mitomycin-C, with cis-platinum, and with bleomycin carries a significant, albeit extremely small, risk for the development of HUS, compared with all other cytotoxic drugs. Gemcitabine is a novel cytotoxic drug with promising activity against pancreatic adenocarcinoma. We are reporting on one patient with metastatic duodenal papillary carcinoma developing HUS while on weekly gemcitabine therapy. The presenting features in this patient were non-cardiac pulmonary oedema, renal failure, thrombocytopenia and haemolytic anaemia. The diagnosis of HUS was made on the day of admission of the patient to this institution. Upon aggressive therapy, including one single haemodialysis and five plasmaphereses, the patient recovered uneventfully, with modestly elevated creatinine-values as a remnant of the acute illness. Re-exposure to gemcitabine 6 months after the episode of HUS instituted for progressive carcinoma, thus far has not caused another episode of HUS. © 1999 Cancer Research Campaig

Sex differences in in-hospital mortality following a first acute myocardial infarction: Symptomatology, delayed presentation, and hospital setting

Background: Women generally wait longer than men prior to seeking treatment for acute myocardial infarction (AMI). They are more likely to present with atypical symptoms, and are less likely to be admitted to coronary or intensive care units (CCU or ICU) compared to similarly-aged males. Women are more likely to die during hospital admission. Sex differences in the associations of delayed arrival, admitting ward, and mortality have not been thoroughly investigated. Methods: Focusing on presenting symptoms and time of presentation since symptom onset, we evaluated sex differences in in-hospital mortality following a first AMI in 4859 men and women presenting to three emergency departments (ED) from December 2008 to February 2014. Sex-specific risk of mortality associated with admission to either CCU/ICU or medical wards was calculated after adjusting for age, socioeconomic status, triage-assigned urgency of presentation, blood pressure, heart rate, presenting symptoms, timing of presentation since symptom onset, and treatment in the ED. Sex-specific age-adjusted attributable risks were calculated.Results: Compared to males, females waited longer before seeking treatment, presented more often with atypical symptoms, and were less likely to be admitted to CCU or ICU. Age-adjusted mortality in CCU/ICU or medical wards was higher among females (3.1 and 4.9 % respectively in CCU/ICU and medical wards in females compared to 2.6 and 3.2 % in males). However, after adjusting for variation in presenting symptoms, delayed arrival and other risk factors, risk of death was similar between males and females if they were admitted to CCU or ICU. This was in contrast to those admitted to medical wards. Females admitted to medical wards were 89 % more likely to die than their male counterparts. Arriving in the ED within 60 min of onset of symptoms was not associated with in-hospital mortality. Among males, 2.2 % of in-hospital mortality was attributed to being admitted to medical wards rather than CCU or ICU, while for females this age-adjusted attributable risk was 4.1 %. Conclusions: Our study stresses the need to reappraise decision making in patient selection for admission to specialised care units, whilst raising awareness of possible sex-related bias in management of patients diagnosed with an AMI

High ALDH Activity Identifies Chemotherapy-Resistant Ewing's Sarcoma Stem Cells That Retain Sensitivity to EWS-FLI1 Inhibition

Cancer stem cells are a chemotherapy-resistant population capable of self-renewal and of regenerating the bulk tumor, thereby causing relapse and patient death. Ewing's sarcoma, the second most common form of bone tumor in adolescents and young adults, follows a clinical pattern consistent with the Cancer Stem Cell model - remission is easily achieved, even for patients with metastatic disease, but relapse remains frequent and is usually fatal.We have isolated a subpopulation of Ewing's sarcoma cells, from both human cell lines and human xenografts grown in immune deficient mice, which express high aldehyde dehydrogenase (ALDH(high)) activity and are enriched for clonogenicity, sphere-formation, and tumor initiation. The ALDH(high) cells are resistant to chemotherapy in vitro, but this can be overcome by the ATP binding cassette transport protein inhibitor, verapamil. Importantly, these cells are not resistant to YK-4-279, a small molecule inhibitor of EWS-FLI1 that is selectively toxic to Ewing's sarcoma cells both in vitro and in vivo.Ewing's sarcoma contains an ALDH(high) stem-like population of chemotherapy-resistant cells that retain sensitivity to EWS-FLI1 inhibition. Inhibiting the EWS-FLI1 oncoprotein may prove to be an effective means of improving patient outcomes by targeting Ewing's sarcoma stem cells that survive standard chemotherapy

Demographic, socio-economic, and cultural factors affecting fertility differentials in Nepal

<p>Abstract</p> <p>Background</p> <p>Traditionally Nepalese society favors high fertility. Children are a symbol of well-being both socially and economically. Although fertility has been decreasing in Nepal since 1981, it is still high compared to many other developing countries. This paper is an attempt to examine the demographic, socio-economic, and cultural factors for fertility differentials in Nepal.</p> <p>Methods</p> <p>This paper has used data from the Nepal Demographic and Health Survey (NDHS 2006). The analysis is confined to ever married women of reproductive age (8,644). Both bivariate and multivariate analyses have been performed to describe the fertility differentials. The bivariate analysis (one-way ANOVA) was applied to examine the association between children ever born and women's demographic, socio-economic, and cultural characteristics. Besides bivariate analysis, the net effect of each independent variable on the dependent variable after controlling for the effect of other predictors has also been measured through multivariate analysis (multiple linear regressions).</p> <p>Results</p> <p>The mean numbers of children ever born (CEB) among married Nepali women of reproductive age and among women aged 40-49 were three and five children, respectively. There are considerable differentials in the average number of children ever born according to women's demographic, socio-economic, and cultural settings. Regression analysis revealed that age at first marriage, perceived ideal number of children, place of residence, literacy status, religion, mass media exposure, use of family planning methods, household headship, and experience of child death were the most important variables that explained the variance in fertility. Women who considered a higher number of children as ideal (β = 0.03; p < 0.001), those who resided in rural areas (β = 0.02; p < 0.05), Muslim women (β = 0.07; p < 0.001), those who had ever used family planning methods (β = 0.08; p < 0.001), and those who had a child-death experience (β = 0.31; p < 0.001) were more likely to have a higher number of CEB compared to their counterparts. On the other hand, those who married at a later age (β = -0.15; p < 0.001), were literate (β = -0.05; p < 0.001), were exposed to both (radio/TV) mass media (β = -0.05; p < 0.001), were richest (β = -0.12; p < 0.001), and were from female-headed households (β = -0.02; p < 0.05) had a lower number of children ever born than their counterparts.</p> <p>Conclusion</p> <p>The average number of children ever born is high among women in Nepal. There are many contributing factors for the high fertility, among which are age at first marriage, perceived ideal number of children, literacy status, mass media exposure, wealth status, and child-death experience by mothers. All of these were strong predictors for CEB. It can be concluded that programs should aim to reduce fertility rates by focusing on these identified factors so that fertility as well as infant and maternal mortality and morbidity will be decreased and the overall well-being of the family maintained and enhanced.</p

Phenotypic Characterization of a Genetically Diverse Panel of Mice for Behavioral Despair and Anxiety

Animal models of human behavioral endophenotypes, such as the Tail Suspension Test (TST) and the Open Field assay (OF), have proven to be essential tools in revealing the genetics and mechanisms of psychiatric diseases. As in the human disorders they model, the measurements generated in these behavioral assays are significantly impacted by the genetic background of the animals tested. In order to better understand the strain-dependent phenotypic variability endemic to this type of work, and better inform future studies that rely on the data generated by these models, we phenotyped 33 inbred mouse strains for immobility in the TST, a mouse model of behavioral despair, and for activity in the OF, a model of general anxiety and locomotor activity.We identified significant strain-dependent differences in TST immobility, and in thigmotaxis and distance traveled in the OF. These results were replicable over multiple testing sessions and exhibited high heritability. We exploited the heritability of these behavioral traits by using in silico haplotype-based association mapping to identify candidate genes for regulating TST behavior. Two significant loci (-logp >7.0, gFWER adjusted p value <0.05) of approximately 300 kb each on MMU9 and MMU10 were identified. The MMU10 locus is syntenic to a major human depressive disorder QTL on human chromosome 12 and contains several genes that are expressed in brain regions associated with behavioral despair.We report the results of phenotyping a large panel of inbred mouse strains for depression and anxiety-associated behaviors. These results show significant, heritable strain-specific differences in behavior, and should prove to be a valuable resource for the behavioral and genetics communities. Additionally, we used haplotype mapping to identify several loci that may contain genes that regulate behavioral despair

Mouse Background Strain Profoundly Influences Paneth Cell Function and Intestinal Microbial Composition

Increasing evidence supports the central role of Paneth cells in maintaining intestinal host-microbial homeostasis. However, the direct impact of host genotype on Paneth cell function remains unclear. Here, we characterize key differences in Paneth cell function and intestinal microbial composition in two widely utilized, genetically distinct mouse strains (C57BL/6 and 129/SvEv). In doing so, we demonstrate critical influences of host genotype on Paneth cell activity and the enteric microbiota.Paneth cell numbers were determined by flow cytometry. Antimicrobial peptide (AMP) expression was evaluated using quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR), acid urea-polyacrylamide gel electrophoresis, and mass spectrometry. Effects of mouse background on microbial composition were assessed by reciprocal colonization of germ-free mice from both background strains, followed by compositional analysis of resultant gut bacterial communities using terminal restriction fragment length polymorphism analysis and 16 S qPCR. Our results revealed that 129/SvEv mice possessed fewer Paneth cells and a divergent AMP profile relative to C57BL/6 counterparts. Novel 129/SvEv á-defensin peptides were identified, including Defa2/18v, Defa11, Defa16, and Defa18. Host genotype profoundly affected the global profile of the intestinal microbiota, while both source and host factors were found to influence specific bacterial groups. Interestingly, ileal α-defensins from 129/SvEv mice displayed attenuated antimicrobial activity against pro-inflammatory E. coli strains, a bacterial species found to be expanded in these animals.This work establishes the important impact of host genotype on Paneth cell function and the composition of the intestinal microbiota. It further identifies specific AMP and microbial alterations in two commonly used inbred mouse strains that have varying susceptibilities to a variety of disorders, ranging from obesity to intestinal inflammation. This will be critical for future studies utilizing these murine backgrounds to study the effects of Paneth cells and the intestinal microbiota on host health and disease

Networks or structures? : organizing cultural routes around heritage values : case studies from Poland

The most common way of managing cultural heritage recently takes form of cultural routes as they seem to offer a new model of participation in culture to their recipients; they are often a peculiar anchor point for inhabitants to let them understand their identity and form the future; they offer actual tours to enter into interaction with culture and history, to build together that creation of the heritage, which so is becoming not only a touristic product, but, first of all, the space for cultural, social and civic activity. Yet, so far, according to what we know, the research problem concerning the method of cultural route organization (points on the route) into solid structures or more of the networked nature, has not been deliberated. A question arises, what values are brought by routes and how to organize routes to be the carriers of the values important for communities, where routes are functioning. And, as a consequence, if, from the point of view of the values of local communities, organizing solid route structures or organizing more widely-spaced, network-based routes would bring effects and what those effects would be. Thus, the posed question is of course scientifically imprecise because a network is a type of structure but presents a given direction for the development of cultural route structures. Our objective here is to present a certain solidity and rigidity of structure with dynamic and smooth understanding of the network. The research presented in the article is based on 3 case studies. We have selected for this purpose the three largest cultural routes in Poland, organized to various degrees. The outcome of the research was referred also to other cultural route organization research

The Meningococcal Vaccine Candidate Neisserial Surface Protein A (NspA) Binds to Factor H and Enhances Meningococcal Resistance to Complement

Complement forms an important arm of innate immunity against invasive meningococcal infections. Binding of the alternative complement pathway inhibitor factor H (fH) to fH-binding protein (fHbp) is one mechanism meningococci employ to limit complement activation on the bacterial surface. fHbp is a leading vaccine candidate against group B Neisseria meningitidis. Novel mechanisms that meningococci employ to bind fH could undermine the efficacy of fHbp-based vaccines. We observed that fHbp deletion mutants of some meningococcal strains showed residual fH binding suggesting the presence of a second receptor for fH. Ligand overlay immunoblotting using membrane fractions from one such strain showed that fH bound to a ∼17 kD protein, identified by MALDI-TOF analysis as Neisserial surface protein A (NspA), a meningococcal vaccine candidate whose function has not been defined. Deleting nspA, in the background of fHbp deletion mutants, abrogated fH binding and mAbs against NspA blocked fH binding, confirming NspA as a fH binding molecule on intact bacteria. NspA expression levels vary among strains and expression correlated with the level of fH binding; over-expressing NspA enhanced fH binding to bacteria. Progressive truncation of the heptose (Hep) I chain of lipooligosaccharide (LOS), or sialylation of lacto-N-neotetraose LOS both increased fH binding to NspA-expressing meningococci, while expression of capsule reduced fH binding to the strains tested. Similar to fHbp, binding of NspA to fH was human-specific and occurred through fH domains 6–7. Consistent with its ability to bind fH, deleting NspA increased C3 deposition and resulted in increased complement-dependent killing. Collectively, these data identify a key complement evasion mechanism with important implications for ongoing efforts to develop meningococcal vaccines that employ fHbp as one of its components

The NS1 Glycoprotein Can Generate Dramatic Antibody-Enhanced Dengue Viral Replication in Normal Out-Bred Mice Resulting in Lethal Multi-Organ Disease

Antibody-enhanced replication (AER) of dengue type-2 virus (DENV-2) strains and production of antibody-enhanced disease (AED) was tested in out-bred mice. Polyclonal antibodies (PAbs) generated against the nonstructural-1 (NS1) glycoprotein candidate vaccine of the New Guinea-C (NG-C) or NSx strains reacted strongly and weakly with these antigens, respectively. These PAbs contained the IgG2a subclass, which cross-reacted with the virion-associated envelope (E) glycoprotein of the DENV-2 NSx strain, suggesting that they could generate its AER via all mouse Fcγ-receptor classes. Indeed, when these mice were challenged with a low dose (<0.5 LD50) of the DENV-2 NSx strain, but not the NG-C strain, they all generated dramatic and lethal DENV-2 AER/AED. These AER/AED mice developed life-threatening acute respiratory distress syndrome (ARDS), displayed by diffuse alveolar damage (DAD) resulting from i) dramatic interstitial alveolar septa-thickening with mononuclear cells, ii) some hyperplasia of alveolar type-II pneumocytes, iii) copious intra-alveolar protein secretion, iv) some hyaline membrane-covered alveolar walls, and v) DENV-2 antigen-positive alveolar macrophages. These mice also developed meningo-encephalitis, with greater than 90,000-fold DENV-2 AER titers in microglial cells located throughout their brain parenchyma, some of which formed nodules around dead neurons. Their spleens contained infiltrated megakaryocytes with DENV-2 antigen-positive red-pulp macrophages, while their livers displayed extensive necrosis, apoptosis and macro- and micro-steatosis, with DENV-2 antigen-positive Kuppfer cells and hepatocytes. Their infections were confirmed by DENV-2 isolations from their lungs, spleens and livers. These findings accord with those reported in fatal human “severe dengue” cases. This DENV-2 AER/AED was blocked by high concentrations of only the NG-C NS1 glycoprotein. These results imply a potential hazard of DENV NS1 glycoprotein-based vaccines, particularly against DENV strains that contain multiple mutations or genetic recombination within or between their DENV E and NS1 glycoprotein-encoding genes. The model provides potential for assessing DENV strain pathogenicity and anti-DENV therapies in normal mice