Influence of Mycobacterium avium subsp. paratuberculosis on colitis development and specific immune responses during disease

The granulomatous and intramural inflammation observed in cases of inflammatory bowel diseases (IBD) and veterinary Johne's disease suggests that Mycobacterium avium subsp. paratuberculosis is a causative agent. However, an incomplete understanding of the immunological steps responsible for the pathologies of IBD makes this conclusion uncertain. Sera from interleukin-10-deficient (IL-10(-/-)) mice with spontaneous colitis displayed significantly higher M. avium subsp. paratuberculosis-specific immunoglobulin G2a antibody responses than did sera from similar mice without disease. Pathogen-free IL-10(-/-) mice received control vehicle or the vehicle containing heat-killed or live M. avium subsp. paratuberculosis. Mucosal CD4(+) T cells from the mice that developed colitis proliferated and secreted higher levels of gamma interferon and tumor necrosis factor alpha after ex vivo stimulation with a Vbeta11(+) T-cell receptor-restricted peptide from the MPT59 antigen (Ag85B) than those secreted from cells from mice before the onset of colitis. The data from this study provide important information regarding the mechanisms of colitis in IL-10(-/-) mice, which are driven in part by Ag85B-specific T cells. The data suggest a plausible mechanism of Ag-specific T-cell responses in colitis driven by potent Ags conserved in Mycobacterium species.     

Penicillium marneffei--an indicator disease of AIDS: a case report

Penicillium marneffei (PM), the only dimorphic species of the genus penicillium is the etiological agent of penicilliosis marneffei. This opportunistic fungal infection occurs among human immunodeficiency virus (HIV) infected and other immunocompromised patient in several regions of South-east Asia, where the infection is considered as an indicator disease of AIDS. A case of penicilliosis marneffei is reported in a patient whose HIV status was unknown and later turned to be in the late stage of AIDS. This demonstrates that it is indeed an indicator disease of AIDS. In India, penicilliosis has been reported among the inhabitants of Manipur state where the prevalence of HIV infection / AIDS is very high. The causative agent was first isolated from a captive bamboo rat. Investigation of the prevalence of the organism among bamboo rats of different countries of South East Asia revealed four species of bamboo rats to be harboring the organism. These four species of bamboo rats are Rhizomys sinensis, R. pruinosus, R. sumatrensis and Cannomys badius. In Manipur, Penicillium marneffei has been isolated from Cannomys badius. Any patient presenting with penicilliosis marneffei should be subjected to HIV counselling and testing if the HIV status is not known and further study regarding the ecology and epidemiology of the fungus is needed.     

Significance of p53 expression in ovarian tumors and its correlation to the morphological differentiation

Cancer of breast and cervix reign supreme among the fatal diseases in women globally. Interestingly the ovarian cancer has the highest mortality rate. This is attributed to its late clinical presentation and delayed diagnosis. The expression of p53 throws light on the prognosis of ovarian tumors. The surface epithelial tumors, especially the serous cystadenocarcinoma and non Hodgkin lymphoma of ovary where in the expression p53 was high compared to the benign and borderline tumors. Further the expression of p53 in tumors arising from germinal cells, sex-cord stromal cells are observed to be very low. The expression of p53 and its correlation to the morphology enhances the prognostic significance.     

Predicting negligence in female sterilization failure using time interval to sterilization failure: analysis of 131 cases

BACKGROUND: Sterilization failure due to 'tubal non-occlusion' or 'wrong structure sterilization' is considered negligent, whereas 'spontaneous tubal recanalization' or 'fistula formation' is considered non-negligent. We examined whether interval to pregnancy failure was predictive of a negligent rather non-negligent failure mechanism. We aim to test this hypothesis in a selected population series of known mechanisms of sterilization failure and their time interval to failure. METHODS: Analyses of 131 failed sterilizations pooled from UK (NHS Litigation Authority, Medical Protection Society and our hospital), Australia and a qualitative systematic review. RESULTS: We identified 88 negligent and 43 non-negligent sterilization failures. Filshie and ring methods failed earlier than diathermy and Pomeroy methods. Sterilization failure occurred significantly earlier in negligent than non-negligent failure mechanisms [median failure intervals 7.0 versus 12.0 months; Hazard ratio (2.35 95% CI 1.31-4.21)]. Knowing that sterilization failure occurred early, increased the probability that the failure mechanism was likely to be negligent rather than non-negligent. CONCLUSIONS: A short interval to failure is suggestive of a negligent failure mechanism. There is less certainty in the predictive value of longer time intervals on the mechanism of failure due to a paucity of cases. A national register of failed sterilizations that have been systematically investigated is needed to improve our understanding of negligent and non-negligent failure mechanisms.     

Impact of Superdisintegrants and Film Thickness on Disintegration Time of Strip Films Loaded With Poorly Water-Soluble Drug Microparticles

Although strip films are a promising platform for delivery of poorly water-soluble drug particles via slurry casting, the effect of critical material attributes, for example, superdisintegrants (SDIs) on critical quality attributes, including film disintegration time (DT), remains underexplored. A 2-level factorial design is considered to examine the impact of the SDI type (sodium starch glycolate and croscarmellose sodium), their amount, and film thickness. SDIs were used with hydroxypropyl methylcellulose (E15LV) and glycerin solutions along with viscosity matching. Fenofibrate, a model poorly water-soluble drug, was micronized and surface modified via fluid energy milling. Significant decreases in film DT, measured using 3 different methods, were observed due to the addition of SDIs. Percentage reduction in DT was a strong function of SDI amount, and thinner films disintegrated faster. Films with either higher SDI concentrations (>9%) or films under 80 μm, exhibited fast DT (<180 s, European Pharmacopeia). All thin films (50-60 μm) exhibited immediate release (>80% in 10 min). All films achieved good content uniformity, except for those with the lowest amount of SDI, attributed to insufficient viscosity and thickness nonuniformity due to the SDI. Finally, all films achieved adequate mechanical properties, notwithstanding minor negative impact of SDIs.     

The influence of MCAT and GPA preadmission academic metrics on interview scores

Medical school admissions interviews are used to assess applicants’ nonacademic characteristics as advocated by the Association of American Medical Colleges’ Advancing Holistic Review Initiative. The objective of this study is to determine whether academic metrics continue to significantly influence interviewers’ scores in holistic processes by blinding interviewers to applicants’ undergraduate grade point averages (uGPA) and Medical College Admission Test (MCAT). This study examines academic and demographic predictors of interview scores for two applicant cohorts at the University of Michigan Medical School. In 2012, interviewers were provided applicants’ uGPA and MCAT scores; in 2013, these academic metrics were withheld from interviewers’ files. Hierarchical regression analysis was conducted to examine the influence of academic and demographic variables on overall cohort interview scores. When interviewers were provided uGPA and MCAT scores, academic metrics explained more variation in interview scores (7.9%) than when interviewers were blinded to these metrics (4.1%). Further analysis showed a statistically significant interaction between cohort and uGPA, indicating that the association between uGPA and interview scores was significantly stronger for the 2012 unblinded cohort compared to the 2013 blinded cohort (β = .573, P < .05). By contrast, MCAT scores had no interactive effects on interviewer scores. While MCAT scores accounted for some variation in interview scores for both cohorts, only access to uGPA significantly influenced interviewers’ scores when looking at interaction effects. Withholding academic metrics from interviewers’ files may promote assessment of nonacademic characteristics independently from academic metrics.     

Torsades de pointes in a patient with Kearns-Sayre syndrome: a fortunate finding

We present a case of a 33-year-old woman with Kearns-Sayre syndrome (KSS) who had a pacemaker implanted for complete heart block postpartum and was found to have torsades de pointes. KSS is a rare encephalomyopathy associated with varying levels of central nervous system involvement, typically resulting in progressive external opthalmoplegia and retinal degeneration. Onset of cardiac conduction disease can be insidious and is a strong predictor of sudden cardiac death. The mainstay of treatment has been the judicious implantation of pacemakers. However, as highlighted in this case, patients who have an underlying cardiomyopathy may be more appropriately treated with an implantable cardioverter defibrillator.