Interpreting cerebrospinal fluid pleocytosis in HIV in the era of potent antiretroviral therapy

Background  

Cerebrospinal fluid (CSF) pleocytosis may be seen in asymptomatic HIV-infected individuals. This finding complicates interpretation of CSF abnormalities when such individuals are evaluated for other central nervous system infections. The goal of this study was to determine the relationship between CSF pleocytosis, central nervous system (CNS) antiretroviral penetration, adherence to antiretroviral medication regimens, neurological symptoms and performance on neuropsychological tests.     

Differential induction of cytochrome P-450 by the enantiomers of trans-stilbene oxide

Optically pure (+)- and (-)-trans-stilbene oxide (TSO) enantiomers were administered to immature male Sprague-Dawley rats. (+)-TSO was the more potent inducer of liver microsomal cytochrome P-450-dependent monooxygenases. The greater potency of (+)-TSO may be explained on the basis of stereoselective metabolism since a far greater concentration of TSO was found in liver microsomes of (+)-TSO-treated rats. Furthermore, of the enzymes known to metabolize TSO, cytosolic epoxide hydrolase turned over the (-)-TSO enantiomer at a faster rate, consistent with the greater persistence of the (+)-enantiomer. Although this report is of chiral effects in potency of enzyme induction, stereoselective metabolism (i.e. disposition) rather than inherent structural characteristics (recognition) may be responsible for these effects.     

Deaths of heroin users in a general practice population

Recent evidence suggests that heroin users in the UK are 16 times more likely to die than otherwise expected, although causes of death are varied. The present investigation examines deaths of heroin users at a large Scottish general practice over a four-year period prior to 1 July 1985. A mortality rate of 9.72 per 1000 heroin-user patients per year was observed, roughly half that previously reported, although this difference did not prove to be statistically significant. A higher proportion of the observed deaths were attributed to heroin, and fewer to the misuse of other drugs, and it is speculated that this may reflect the practice's policy of not prescribing opiates to heroin users. Factors associated with heroin-user deaths are examined and areas identified where general practitioners may help to avert some of these deaths.     

Levels of Psychological Distress Experienced by Family Carers of Children and Adolescents with Intellectual Disabilities in an Urban Conurbation

Background The aim of the present study was to identify factors associated with the level of psychological distress reported by family carers of children with intellectual disability living in a large urban conurbation. Method Information was collected by postal questionnaire (or interview for family carers who did not have English as their first language) from the family carers of 408 children with intellectual disability (31% of all children within the area administratively identified as having an intellectual disability). Results Results indicated that 47% of primary carers scored above the threshold for psychological distress on the GHQ and that scoring above the threshold was strongly related to the emotional and behavioural needs of the index child and South‐Asian ethnicity and moderately associated with the severity of the child's delay in communication. Conclusions The rates of psychological distress (47% overall, 70% among South‐Asian carers) were markedly higher than that found in previous studies of carers supporting a child with intellectual disabilities. It is suggested that these elevated rates of psychological distress may be mediated by socio‐economic deprivation.     

Successful immune reconstitution decreases leukemic relapse and improves survival in recipients of unrelated cord blood transplantation.

Allogeneic hematopoietic stem cell transplantation (HSCT) is established therapy for selected patients with acute leukemia. After transplantation, antileukemic immune responses are believed to eliminate residual leukemia cells and decrease the likelihood of relapse. However, the clinical effect of successful antigen-specific immune reconstitution after HSCT on the likelihood of leukemic relapse and overall survival is not known. Pediatric recipients of unrelated cord blood transplants who underwent transplantation for acute leukemia were sequentially evaluated for their development of antigen-specific T-lymphocyte immunity to herpes viruses. The clinical effect of a positive antigen-specific response on relapse-free survival was determined. The presence of an antigen-specific response resulted in a relapse-free survival advantage (P = .0001), which was primarily due to a decrease in leukemic relapse (P = .003). Proportional hazards modeling for time to relapse and time to relapse or death defined 3 variables that were strongly associated with a poor outcome: female gender, poor remission status before transplantation, and negative antigen-specific T-lymphocyte proliferation. Notably neither acute nor chronic graft-versus-host disease had any effect on the incidence of leukemic relapse. Successful antigen-specific immune reconstitution after unrelated cord blood transplantation results in decreased leukemic relapse and improved overall survival.     

Bioethics for clinicians: 5. Substitute decision-making.

Substitute decision-making is a means of making health care decisions on behalf of people who are incapable of making these decisions for themselves. It is based on the ethical principle of respect for autonomy. Substitute decision-making poses two main questions: Who-should make the decision for the incapable person, and, How should the decision be made? Because the applicable statutory and common law varies across Canada, clinicians should become familiar with the legal requirements of their own province or territory.     

Recombinant erythropoietin improves exercise capacity in anemic hemodialysis patients

The objective of this study was to quantitate the improvement in exercise capacity produced in anemic chronic hemodialysis (HD) patients after correction of their anemia with recombinant human erythropoietin (rHuEPO). The maximal exercise capacity and quadriceps strength of 19 anemic HD patients was tested before and after correction of the anemia with rHuEPO. A progressive work exercise protocol (PWET) on a cycle ergometer was used to compare measurements of maximal oxygen uptake (VO2max), maximal heart rate, and subjective assessment of fatigue during the test. Measurements of quadriceps strength were performed before the cycle ergometer studies. At baseline, all patients had reduced VO2max (15.3 +/- 5.4 mL/kg/min) and maximal exercise heart rates (138.5 +/- 23.9 beats/min). rHuEPO increased the mean hematocrit from 21.2% to 35%, and this was associated with a 17% increase (P less than 0.0005) in the VO2max. At any specified work load, rHuEPO treatment decreased heart rate, minute ventilation, and the subjective perception of fatigue. Both isometric and isokinetic measurements of quadriceps strength were improved following administration of rHuEPO. The maximal exercise heart rate was decreased in comparison to the baseline measurements (P less than 0.04), suggesting that in contrast to normal subjects, HD patients stop exercise before oxygen transport limitations are reached. In this unselected group of chronic HD patients, rHuEPO produced clinically significant improvements in both aerobic exercise capacity and isometric and isokinetic quadriceps strength. The improvement in aerobic capacity was substantially less than would have been expected from the correction of a comparable degree of anemia in non-HD patients. None of the 19 treated patients attained the exercise performance level predicted for a sedentary normal subject.