Evidence for expansion of a population of lymphocytes with reduced or absent T3 expression in aged human donors

In a previous report, we described an unusual pattern of T cell associated surface marker expression in unfractionated mononuclear cells from aged donors; an excess of T4 and T8 positive cells relative to T3 positive cells. This study further characterizes these cells on the basis of density, adherence to nylon wool and quantitative expression of cell surface markers. We find that the population of lymphocytes responsible for the unusual surface marker expression is of low density, adheres to nylon wool, and is present in small numbers in young donors. The adherent cells have a reduced quantitative expression of the T3 antigen, no change in the antigen density of T4 and T8, and have increased expression of the T10 antigen. These cells do not have the characteristics of large granular lymphocytes, monocytes, B cells with unusual marker expression, or thymocytes poised for export to peripheral blood. We suggest that these cells, found in increased numbers in aged humans, may represent an expansion of a population of T lymphocytes with absent or reduced T3 antigen expression found normally in smaller numbers in young adults. T lymphocyte antigen receptor density has been quantitatively linked to expression of the T3 antigen. Thus, our results imply that aging may lead to decreased T cell surface antigen density, which may account in part for decline in T cell function with age.     

A vignette study to examine health care professionals' attitudes towards patient involvement in error prevention

Background Various authorities recommend the participation of patients in promoting patient safety, but little is known about health care professionals' (HCPs') attitudes towards patients' involvement in safety‐related behaviours. Objective To investigate how HCPs evaluate patients' behaviours and HCP responses to patient involvement in the behaviour, relative to different aspects of the patient, the involved HCP and the potential error. Design Cross‐sectional fractional factorial survey with seven factors embedded in two error scenarios (missed hand hygiene, medication error). Each survey included two randomized vignettes that described the potential error, a patient's reaction to that error and the HCP response to the patient. Setting Twelve hospitals in Switzerland. Participants A total of 1141 HCPs (response rate 45%). Measurements Approval of patients' behaviour, HCP response to the patient, anticipated effects on the patient–HCP relationship, HCPs' support for being asked the question, affective response to the vignettes. Outcomes were measured on 7‐point scales. Results Approval of patients' safety‐related interventions was generally high and largely affected by patients' behaviour and correct identification of error. Anticipated effects on the patient–HCP relationship were much less positive, little correlated with approval of patients' behaviour and were mainly determined by the HCP response to intervening patients. HCPs expressed more favourable attitudes towards patients intervening about a medication error than about hand sanitation. Conclusions This study provides the first insights into predictors of HCPs' attitudes towards patient engagement in safety. Future research is however required to assess the generalizability of the findings into practice before training can be designed to address critical issues.     

The management of moderate to severe atopic dermatitis in adults with topical fluticasone propionate

This study was designed to investigate a long-term therapeutic strategy for the management of recurring atopic dermatitis (AD) in adults using fluticasone propionate (FP) ointment (Cutivate^TM) whereby FP could help to prevent a relapse of AD once symptoms were under control. Adult patients with chronic, moderate to severe AD entered this multicentre study. All patients were initially treated with FP 0.005% (g/g) ointment in two different regimens. Patients whose AD had been completely healed by these treatments then entered a long-term treatment phase applying FP or placebo ointment once daily, two times per week for 16 weeks to 'known' healed lesions. By the end of the initial treatment period, mean SCORAD values had significantly ( P  < 0.0005) improved from baseline. Patients who entered the maintenance phase and were treated with intermittent FP for up to 16 weeks, demonstrated its superior efficacy ( P  = 0.018) over placebo, maintaining the improvements achieved after the initial treatment phase, reducing risk of relapse and delaying time to relapse ( P  = 0.013). No significant changes were detected in either treatment group in serum cortisol levels or in skin thickness measurements. Intermittent FP applied two times per week maintained a significant level of control, and delayed relapse of AD by comparison with placebo.     

CD40 upregulation is independent of HHV-8 in the pathogenesis of Kaposi's sarcoma.

AIMS: Human herpesvirus 8 (HHV-8) is now acknowledged as the infective cofactor in the pathogenesis of Kaposi's sarcoma. The mode by which HHV-8 causes Kaposi's sarcoma is unresolved and it is probable that it acts in conjunction with other factors including cytokines, anti-apoptosis proteins, and cell surface receptors. CD40, a cell membrane receptor belonging to the tumour necrosis factor receptor super family, promotes B cell survival and is expressed constitutively on endothelial cells. It is upregulated on cytokine treatment and has been documented recently in Kaposi's sarcoma. Because the HHV-8 genome contains cytokine homologues, this study investigated whether CD40 expression in Kaposi's sarcoma correlated with HHV-8 status, using a unique set of HHV-8 positive and negative specimens. METHODS: Twenty one paraffin wax embedded samples of Kaposi's sarcoma were selected, of which 18 were screened for the presence of HHV-8 using both conventional solution phase and TaqMan polymerase chain reaction (PCR). CD40 immunohistochemistry was assessed using a biotinylated amplification system. Staining was scored semiquantitatively. RESULTS: The results indicated that the expression of CD40 is independent of viral status, being present in both HHV-8 positive and negative specimens. CONCLUSIONS: This suggests that HHV-8 promotes Kaposi's sarcoma cell survival following infection by mechanisms other than those involving CD40.