Longitudinal assessment of cytomegalovirus (CMV)-specific immune responses in liver transplant recipients at high risk for late CMV disease

Cytomegalovirus (CMV)-seronegative recipients (R(-)) of a liver transplant from CMV-positive donors (D(+)) are at high risk for developing late CMV disease after discontinuation of antiviral prophylaxis. Levels of viremia and CMV-specific interferon (IFN)- gamma -producing CD4(+) and IFN- gamma -producing CD8(+) T cell responses were prospectively measured from discontinuation of antiviral prophylaxis until 1 year after transplantation in 17 consecutive D(+)/R(-) patients. CMV loads of >1000 copies/mL were strongly associated with CMV disease in the 6 symptomatic patients. Despite immunosuppression, broadly diverse T cells specific for CMV lysate or peptide libraries spanning pp65 and immediate early (IE) 1 immunodominant CMV antigens developed in all patients. A vigorous CD8(+) T cell response to pp65 and IE1 antigens characterized the D(+)/R(-) cohort. Unexpectedly, none of these responses were predictive of CMV disease or viremia. No significant lymphopenia or functional impairment of CMV-specific T cells was detected in the symptomatic patients, whose morbidity was resolved after antiviral treatment while measurable CMV immunity was maintained during the 1-year observation period.     

Supporting home-based meal preparation improves lunchtime habits and self-assessed work performance of interns at a tertiary hospital

There is ample evidence that doctors frequently miss meals at work, which negatively impacts concentration, decision-making and overall patient care. Junior doctors are particularly vulnerable given their heavy workload. We report on the impact of a pilot programme supporting home-based meal preparation on the dietary habits and energy levels of interns at a tertiary hospital and demonstrate this is one strategy healthcare organisations can adopt to promote a healthier workforce.     

Sphingosine kinase-1 enhances endothelial cell survival through a PECAM-1-dependent activation of PI-3K/Akt and regulation of Bcl-2 family members

Sphingosine-1-phosphate (S1P), the bioactive product of sphingosine kinase (SK) activation, is a survival factor for endothelial cells. The mechanism of SK-mediated survival was investigated in endothelial cells with moderately raised intracellular SK activity. Overexpression of SK mediated survival primarily through the activation of the phosphatidyl inositol 3-kinase (PI-3K)/protein kinase B (Akt/PKB) pathway and an associated up-regulation of the antiapoptotic protein B cell lymphoma gene 2 (Bcl-2) and down-regulation of the proapoptotic protein bisindolylmaleimide (Bcl-2 interacting mediator of cell death; Bim). In addition there was an up-regulation and dephosphorylation of the junctional molecule platelet endothelial cell adhesion molecule-1 (PECAM-1), which was obligatory for activation of the PI-3K/Akt pathway, for SK-induced cell survival, and for the changes in the apoptosis-related proteins. Thus, raised intracellular SK activity induced a molecule involved in cell-cell interactions to augment cell survival through a PI-3K/Akt-dependent pathway. This is distinct from the activation of both PI-3K/Akt and mitogen-activated protein kinase (MAPK) pathways seen with exogenously added S1P. Cells overexpressing SK showed enhanced survival under conditions of serum deprivation and absence of attachment to extracellular matrix, suggesting a role for SK in the regulation of vascular phenomena that occur under conditions of stress, such as angiogenesis and survival in unattached states, as would be required for a circulating endothelial cell.     

Evaluation of hand function in patients undergoing long term haemodialysis

OBJECTIVE: Haemodialysis is associated with the deposition of beta(2) microglobulin in musculoskeletal structures, leading to the syndrome of dialysis related amyloidosis and impairment of hand function. This study aimed at assessing hand function using the Sollerman test in a cross section of patients undergoing haemodialysis. METHODS: Recipients of haemodialysis underwent the Sollerman test of hand grip function, which assesses 20 activities of daily living using eight grip types, and the JAMAR grip strength test, visual analogue scales (VAS) for pain (VAS-P) and function (VAS-F), and Health Assessment Questionnaire (HAQ) were determined. Results-Thirty five subjects (26 male), with mean age 53.2 years, participated. The average duration of haemodialysis was 6.2 years (range one month to 25 years). The median Sollerman score was 77, with 19/35 (54%) patients receiving haemodialysis having a score below the lower normal value of 78-80. The log Sollerman score correlated poorly with age (rs=0.16, p=0.35), and significantly with the HAQ score (r(s)=-0.66, p<0.00005), duration of haemodialysis (rs=-0.39, p<0.05), VAS-F (rs=-0.41, p<0.05), VAS-P (rs=-0.34, p<0.05), and JAMAR score (rs=0.57, p<0.05). Sollerman scores were highly correlated between dominant and non-dominant hands (rs=0.69, p<000005). CONCLUSIONS: Hand dysfunction is a common finding among patients undergoing long term haemodialysis. The Sollerman test accurately reflects patient function as measured by HAQ, VAS-F, and grip strength, but less so pain. Its use for the early detection of dialysis related amyloidosis and in the serial monitoring of the effects of hand treatment programmes is encouraged.     

High incidence of ganciclovir-resistant cytomegalovirus infection among lung transplant recipients receiving preemptive therapy.

Preemptive antiviral therapy in transplant patients is thought to be less likely to lead to antiviral resistance than is routine prophylaxis. Cytomegalovirus (CMV)-seropositive lung transplant patients (R+) were assigned to receive pp65 antigen-guided ganciclovir therapy, and seronegative recipients of organs from seropositive donors (D+/R-) were assigned to receive initially preemptive and then routine ganciclovir prophylaxis. The incidence of infection with ganciclovir-resistant (ganR) CMV was assessed retrospectively. GanR CMV infection developed in 4 (9%) of 45 patients, at a median of 4.4 months (range, 3.1-6.6 months) after transplantation, and was more common among D+/R- patients than among R+ patients (3 of 11 vs. 1 of 34; P =.04). The incidence among patients who received preemptive therapy was similar to that among patients who received routine prophylaxis. All ganR isolates contained a UL97 mutation. GanR CMV infection occurs in nearly 10% of lung transplant recipients, despite preemptive antiviral therapy, and is more common among D+/R- patients.     

Lack of knowledge about diabetes in Pune—the city of knowledge!

India is experiencing an escalating epidemic of diabetes for which the most cost-effective solution is prevention. Awareness is the first step towards prevention. We undertook a questionnaire-based study to evaluate gaps in awareness of different implications of diabetes among various sections of the urban population of Pune. Individuals aged ≥13 years (378 diabetic, 1122 non-diabetic) from different socio-economic backgrounds were interviewed using a structured questionnaire. Awareness regarding causes, symptoms, complications, treatment and preventive measures, curability of diabetes and long-term implications of diabetes in pregnancy was evaluated. An awareness score was calculated based on the percent of total questions correctly answered. Of those surveyed, 78 % scored less than 50 %, 44 % did not know the meaning of diabetes, 30 % could not name any of the risk factors, symptoms, complications and preventive measures for diabetes, and 70 % were unaware of the long-term risks of diabetes in pregnancy. As a group, diabetic participants scored marginally better than non-diabetic participants (mean score 39 vs. 31 %; P?<?0.001). Participants at high risk of diabetes (sedentary workers, non-diabetic participants with first-degree family history of diabetes and non-diabetic hypertensive participants) had poor knowledge about the condition (mean scores <40 %). Lower age, lower education and male gender were independently associated with poor awareness; education was the strongest predictor. Awareness regarding different implications of diabetes is poor in the population of Pune. There is a need for widespread and extensive public education campaigns to raise awareness and contribute to the national diabetes prevention initiatives.