Inhibitory effect of cystic fibrosis sputum on adenovirus-mediated gene transfer in cultured epithelial cells.

Effective gene transfer to the airway epithelial cells of individuals with cystic fibrosis (CF) requires gene therapy vectors to effectively penetrate the mucous lining of the airways of these patients. In this study, we examined the effects of the aqueous sol fraction of sputum recovered from CF patients (CF sol) on adenovirus (Ad)-mediated gene transfer to cultured epithelial cells. Sputum collected from patients with CF was separated into aqueous sol and gel fractions by ultracentrifugation and the sol fraction from different individuals was pooled. To determine if CF sol affects Ad-mediated transfection, Fisher rat thyroid (FRT) epithelial cells or normal human bronchial epithelial (NHBE) cells were infected with an Ad encoding beta-galactosidase (Ad2/betagal-2) in the presence or absence of the pooled CF sol. Transfection efficiency was determined by measuring beta-Gal activity. CF sol significantly inhibited Ad2-mediated gene transfer in a dose-dependent manner when the vector was incubated with CF sol prior to exposure to the cells. In contrast, preincubation of the cells with the sol was without effect. The inhibition of Ad-mediated gene transfer by CF sol was not related to its low pH, was abrogated by preadsorption with an Ad2 serotype vector, and was neutralized by heat treatment, but was not affected by treatment with protease inhibitors. Analysis of CF sol fractions from seven different individuals with CF showed inhibition of Ad-mediated gene transfer in four of the seven samples tested and, further, the inhibitory effect was correlated with the presence of Ad-specific antibodies. We conclude that preexisting adenovirus-specific antibodies present in some of the patient samples were the predominant factor inhibiting Ad-mediated gene transfer.

Depression, perception of illness and mortality in patients with end-stage renal disease.

A role of depression in affecting outcome in patients with end stage renal disease (ESRD) has been suggested but few have assessed psychological parameters and medical factors thought to influence survival simultaneously and prospectively. To assess whether depression or perception of illness influences survival in patients treated for ESRD, we prospectively evaluated fifty-seven patients with ESRD treated with hemodialysis (HD, n = 43) or continuous ambulatory peritoneal dialysis (CAPD, n = 14). Patients were interviewed and completed the Beck Depression Inventory (BDI) and the Illness Effects Questionnaire (IEQ). An ESRD severity coefficient was used to measure chronic illness severity. A cognitive item subset of the BDI (CDI) was used as an additional measure of depression. One and two years later, records were examined to determine survival. When initial results of the assessment of survivors and non-survivors were compared, at one year follow-up, there were no differences in mean age, duration of dialysis, severity scores, BDI or IEQ scores. The initial mean CDI scores in the group of non-survivors, however, were significantly greater than the scores in the survivor group. At two year follow-up, CDI scores were significantly different between groups, and were significant in a hazards regression. Disease severity, age and duration of dialysis were also significantly related to mortality at two year follow-up. We conclude cognitive depression is an important, early, indicator of grave prognosis in patients treated for ESRD. Early recognition of and therapeutic efforts directed toward the treatment of depression might modify outcome in ESRD patients.

Perception of illness and depression in chronic renal disease.

The causes, extent, and quantification of depression in end-stage renal disease (ESRD) patients have been a concern of psychologists and physicians. To assess depression and its possible causes, 57 patients with ESRD treated with hemodialysis (HD, n = 43) or continuous ambulatory peritoneal dialysis (CAPD, n = 14) and 16 patients with chronic renal insufficiency (CRI) were interviewed and completed the Beck Depression Inventory (BDI) and the Illness Effects Questionnaire (IEQ). An ESRD severity coefficient was used to measure chronic illness severity in the patients treated with dialysis, and blood urea nitrogen (BUN) and creatinine levels were used to assess severity of renal disease and adequacy of treatment. A cognitive item subset of the BDI (CDI) was used as a measure of depression. When patients treated with HD and CAPD were compared, CAPD patients were younger, had a shorter duration of dialysis treatment, and less severe medical illness, but the groups did not differ on the IEQ, BDI, or CDI. The IEQ did not correlate with age or disease variables. Both the CDI and the total BDI scores correlated with the IEQ. Perception of illness (IEQ) correlated significantly with cognitive depression for the CAPD and HD patients. For CAPD patients only, a significant correlation between the IEQ and severity of medical illness was obtained. Perception of illness and creatinine concentration were strongly correlated with cognitive depression in the patients with CRI as well. For all renal patients, level of depression was more strongly related to perception of illness than physical illness variables.(ABSTRACT TRUNCATED AT 250 WORDS)