Impact of OKT3 therapy on cytomegalovirus and herpes simplex virus infections after liver transplantation

The purpose of this study was to analyze the impact of OKT3 on the frequency and severity of CMV and herpes simplex virus (HSV) infections in adult liver transplant recipients. OKT3 treatment is associated with a higher risk of disseminated CMV infection, particularly in patients with primary CMV infection. It also increased the frequency of symptomatic HSV infection in HSV-seropositive liver transplant recipients

Lung function, symptoms and inflammation during exacerbations of non-cystic fibrosis bronchiectasis: a prospective observational cohort study.

Exacerbations of non-cystic fibrosis bronchiectasis cause significant morbidity but there are few detailed data on their clinical course and associated physiological changes. The biology of an exacerbation has not been previously described

Fungal infections after liver transplantation

The risk factors for development of invasive fungal infections after liver transplantation were (1) longer duration of treatment with nonprophylactic IV antibiotics, (2) longer cumulative surgical time and a higher number of laparotomies, (3) an increased number of units of RBCs and fresh-frozen plasma, and (4) a series of pretransplant laboratory findings: thrombocytopenia, low T lymphocyte levels, low CD4 helper cell and lower helper/suppressor cell ratios and IgA serum levels. The significance of some of these findings is still unclear. Attention to the risk factors outlined earlier may aid both in preventing and in the early detection of invasive fungal infections after liver transplantation

Complex regulation of neutrophil-derived MMP-9 secretion in central nervous system tuberculosis.

BACKGROUND: Central nervous system tuberculosis (CNS-TB) may be fatal even with treatment. Neutrophils are the key mediators of TB immunopathology, and raised CSF matrix metalloproteinase-9 (MMP-9) which correlates to neutrophil count in CNS-TB is associated with neurological deficit and death. The mechanisms by which neutrophils drive TB-associated CNS matrix destruction are not clearly defined. METHODS: Human brain biopsies with histologically proven CNS-TB were stained for neutrophils, neutrophil elastase, and MMP-9. Neutrophil MMP-9 secretion and gene expression were analyzed using Luminex and real-time PCR. Type IV collagen degradation was evaluated using confocal microscopy and quantitative fluorescent assays. Intracellular signaling pathways were investigated by immunoblotting and chemical inhibitors. RESULTS: MMP-9-expressing neutrophils were present in tuberculous granulomas in CNS-TB and neutrophil-derived MMP-9 secretion was upregulated by Mycobacterium tuberculosis (M.tb). Concurrent direct stimulation by M.tb and activation via monocyte-dependent networks had an additive effect on neutrophil MMP-9 secretion. Destruction of type IV collagen, a key component of the blood-brain barrier, was inhibited by neutralizing neutrophil MMP-9. Monocyte-neutrophil networks driving MMP-9 secretion in TB were regulated by MAP-kinase and Akt-PI3 kinase pathways and the transcription factor NF-kB. TNFα neutralization suppressed MMP-9 secretion to baseline while dexamethasone did not. CONCLUSIONS: Multiple signaling paths regulate neutrophil-derived MMP-9 secretion, which is increased in CNS-TB. These paths may be better targets for host-directed therapies than steroids currently used in CNS-TB

BIOLOGICS (BIOLOGICAL AGENTS): A NEW APPROACH IN THE TREATMENT OF PSORIASIS

ABSTRACTPsoriasis is a chronic inflammatory and multifactorial systemic disorder with predominant manifestation over the skin and/or joints resulting frominteractions between genetic pre-disposition and triggering environmental factors. Due to its systemic nature, patients exhibit a broad spectrum ofsymptoms that vary in severity. Although many patients, particularly those with the limited form of the disease, may be treated with topical therapy,those with extensive (moderate to severe) psoriasis eventually require phototherapy, systemic, or biologic therapy to adequately suppress the systemic,immunopathogenic process. Biological agents (biologics or biologicals) are a set of different engineered proteins. These are immunosuppressiveagents, designed to selectively interfere with the immune mechanisms that induce psoriasis. Their use is restricted to the treatment of moderateto severe psoriasis, which has failed to respond to systemic therapies (and/or phototherapy) or where such treatments are contra-indicated ornot tolerated. Biologics are becoming increasingly useful for the treatment of many skin diseases including psoriasis, particularly as alternativesfor patients who have failed to tolerate or respond to conventional systemic therapies or where non-biologic systemic agents are unsuitable due tothe presence of comorbidities. Biological therapies provide a targeted approach to treatment through interaction with specific components of theunderlying immune and inflammatory disease processes.Keywords: Immunopathogenesis, Biologicals, Psoriasis, Quality of life, Psoriasis area and severity index, Dermatology life quality index

Infections with cytomegalovirus and other herpesviruses in 121 liver transplant recipients: Transmission by donated organ and the effect of OKT3 antibodies

One hundred twenty-one adult liver transplant recipients were studied for the incidence, risk factors, and morbidity associated with herpesviruses infections after transplantation. The overall incidence of infection was 59% for cytomegalovirus (CMV), 35% for herpes simplex virus (HSV), 25% for Epstein-Barr virus (EBV), and 7% for varicella-zoster virus (VZV). Primary CMV infection occurred in 46% and reactivation CMV infection in 67% of the susceptible recipients. Symptomatic and disseminated CMV diseases were more common when patients developed primary infection (P .10). Although most HSV infections were oral or genital reactivations, three cases of HSV hepatitis occurred - one was primary infection. Symptomatic reactivations of HSV were observed in 53% of HSV-seropositive recipients who received OKT3, versus 31% of seropositive recipients who did not receive OKT3 (P = .05)

Effect of Crop Establishment Methods on Crop Yield, Weed Dynamics, Profitability and Nutrient Uptake Under Rice-Wheat Cropping System of Indo-Gangetic Plains of Eastern India

The rice–wheat cropping system covering 13.5 million ha in the Indo-Gangetic Plains in South-Asia is vital for food security. Water, energy and labour scarcity, increasing cost of production, diminishing farm profit and the changing climate are major challenges faced by the farmers under intensive tillage based conventional practices. In a field study, we evaluated productivity, weed dynamics, nutrient uptake and economical profitability of four wheat establishment methods during two years. The wheat establishment methods included zero-till wheat (ZTW), happy seeder planted wheat (HSW), bed planted wheat (BPW) and conventional till wheat (CTW). The treatments were completely randomized and replicated five times. Wheat grain yield under HSW was 3.4% and 4.1% higher than BPW, 8.3% and 11.0% higher than ZTW and 20.8% and 24.5% higher than CTW in 2012-13 and 2013-14, respectively. Nutrient (N, P and K) uptake in wheat grain was also higher in HSW than in the other treatments. Weed density and biomass was the lowest under HSW followed by BPT, and the highest in CTW. The weed pressure was reduced in the second growing season compared to the first. Net profit and benefit cost ratio was highest under HSW and the lowest under CTW. This record was migrated from the OpenDepot repository service in June, 2017 before shutting down

Clinical and molecular features associated with cystic visceral lesions in von hippel-lindau disease.

Von Hippel-Lindau (VHL) is an uncommon oncogenic disorder which occurs as a result of genetic mutations on chromosome 3p. Retinal capillary haemangiomas and CNS haemangioblastomas have been well-characterised in genotypic-phenotypic analyses, but cystic visceral lesions are less common and have been less frequently studied. The aim of this study was to perform genotypic and phenotypic analysis of a cohort of VHL patients that developed cystic visceral lesions to determine whether their genotype differs from that seen in other manifestations of VHL and whether the ocular manifestations differ.This study reports a prospective case series of twenty-one patients identified from the Hammersmith Hospital Genetics Service database as having VHL mutations. Patients underwent regular ocular and systemic screening as well as genotypic analysis. The main outcome measures were the development of VHL lesions, either ocular or systemic.Cystic visceral lesions were detected in six of the 21 patients from the clinic (29%). These included renal cysts in four patients, pancreatic cysts in three patients, and an epididymal cystadenoma in one patient. Renal cysts were not associated with any specific genotype. Pancreatic cysts appeared to occur in association with VHL gene deletions and all developed CNS haemangioblastomas. Only one patient developed ocular manifestations, which occurred in this patient in the form of two retinal capillary haemangiomas.VHL gene deletions appeared to be associated with pancreatic cysts and the development of CNS haemangioblastomas. Ocular manifestations are uncommon in this group of patients