Hepatotoxicity in HIV-infected children and adolescents on antiretroviral therapy.

CONTEXT AND OBJECTIVE: Adverse drug reactions are a significant problem in patients on antiretroviral therapy (ART). We determined liver enzyme elevation frequencies in HIV-infected children and adolescents receiving ART, and their association with risk factors. DESIGN AND SETTING: Cross-sectional study, at the Pediatrics Immunodeficiency Division, University Hospital, Universidade Estadual de Campinas. METHODS: Medical records of 152 children and adolescents (54.6% male; median age 7.48 years) were analyzed, with a mean of 2.6 liver enzyme determinations per patient. Clinically, patients were classified in categories N (6), A (29), B (78) and C (39). Serum levels of aspartate aminotransferase and alanine aminotransferase were evaluated. Hepatotoxicity was scored as grade 1 (1.1-4.9 times upper limit of normality, ULN), grade 2 (5.0-9.9 times ULN), grade 3 (10.0-15.0 times ULN) and grade 4 (> 15.0 times ULN). To assess hepatotoxicity risk factors, odds ratios (OR) and adjusted odds ratios (aOR) for age, gender, TCD4+ cell count, viral load and medication usage were calculated. RESULTS: We observed grade 1 hepatotoxicity in 19.7 % (30/152) patients. No cases of grade 2, 3 or 4 were detected. There was a significant association between hepatotoxicity and use of sulfonamides (OR, 3.61; 95% confidence interval (CI), 1.50-8.70; aOR, 3.58; 95% CI, 1.44-8.85) and antituberculous agents (OR, 9.23; 95% CI, 1.60-53.08; aOR, 9.05; 95% CI, 1.48-55.25). No toxicity was associated with ART. CONCLUSIONS: One fifth of patients experienced mild hepatotoxicity, attributed to antituberculous agents and sulfonamides. Our results suggest that ART was well tolerated.     

Comparison between Low Frequency Magnetic Field Stimulation and Nerve Growth Factor Treatment of Cultured Chromaffin Cells, on Neurite Growth, Noradrenaline Release, Excitable Properties, and Grafting in Nigrostriatal Lesioned Rats

Adrenal chromaffin cells in vitro respond to nerve growth factor (NGF) by expressing neuronal traits. Low frequency magnetic (LFM) field stimulation, while inducing a variety of effects on several cell types, has never been studied as to its effects on chromaffin cell cultures. The purpose of this study was to compare the effects of LFM field stimulation with that of NGF on the morphological phenotype, on noradrenaline (NA) release, and on membrane excitability of cultured chromaffin cells. We also tested the effects of grafting LFM and NGF-treated chromaffin cells into the caudate nucleus of rats with 6-hydroxydopamine lesions of the nigrostriatal pathway. The results of this study showed that LFM field stimulation produced neurite growth of cultured chromaffin cells in a manner similar to that of NGF exposure. The combination of the two procedures did not induce changes above those observed by NGF alone. Both NGF- and LFM-treated chromaffin cells released [³H]NA equally in response to a depolarizing concentration of KCl. On the other, Na⁺ current density of LFM field stimulation increased, but to a lesser extent than that seen in NGF-treated cells. In addition both types of cells when transplanted into nigrostriatal-lesioned animals induced a similar decrease in the motor asymmetries produced by the lesion. When NGF- or LFM-treated chromaffin cells where compared to untreated control cells, no significant differences were observed in [³H]NA release, on Na⁺ current densities, or on postgraft motor asymmetries. The results are discussed in terms of the fact that LFM-stimulated cells can be differentiated in a manner similar to NGF-treated cells, by acquiring sympathetic like traits which in turn can diminish motor asymmetries when grafted into nigrostriatal-lesioned rats.     

Effect of family role on response to disaster

This study hypothesized that family role (marital and parental status) would moderate the effect of disaster exposure on the mental health of victims. The study included St. Louis residents exposed to floods and dioxin, as well as Puerto Rican respondents exposed to floods and mudslides. In St. Louis, worst outcomes were found for single and married parents exposed to disaster, substantially exceeding the symptomatology of all unexposed respondents except non-victim single parents. In Puerto Rico, victims without families had higher levels of alcohol abuse symptoms than did any other subgroup. Perceived emotional support was found to be an important moderator of disaster's effect on psychiatric distress in this site, generally overriding the effect of family role. Single parents in both sites who were exposed to disaster had substantially reduced levels of emotional support available to them, as compared to unexposed single parents, suggesting that single parents are at particularly high risk for losing access to emotional support following a disaster. This study suggests that both single and married parents constitute important high-risk victim groups. The findings also suggest that those perceiving they lack adequate emotional support, regardless of family role, may be in special need of services.     

Hypertrophic pulmonary osteoarthropathy in acquired immunodeficiency syndrome. Case report and review

We describe a case of hypertrophic pulmonary osteoarthropathy (HPOA) in an adult patient with acquired immunodeficiency syndrome (AIDS). This is the ninth case of HPOA associated with AIDS in adults, reported in the literature. The presence of pulmonary tuberculosis was also suspected, based on clinical grounds. Cases of clubbing associated with AIDS infection are reviewed.     

Comparison of the QUANTIPLEX HIV-1 RNA 2.0 Assay with the AMPLICOR HIV-1 MONITOR 1.0 Assay for Quantitation of Levels of Human Immunodeficiency Virus Type 1 RNA in Plasma of Patients Receiving Stavudine-Didanosine Combination Therapy

We compared the QUANTIPLEX HIV-1 RNA 2.0 assay with the AMPLICOR HIV-1 MONITOR 1.0 assay for quantitation of human immunodeficiency virus type 1 (HIV-1) RNA in plasma in the Stadi trail, which evaluated a stavudine plus didanosine combination therapy in 52 patients. HIV-1 RNA baseline values measured with AMPLICOR HIV-1 MONITOR 1.0 were significantly higher than those measured with QUANTIPLEX HIV-1 RNA 2.0, and decreases in HIV-1 RNA levels from baseline were also found to be significantly higher when measured with the AMPLICOR HIV-1 MONITOR 1.0 assay. The frequency of HIV-1 RNA levels below the lower limit of quantitation was significantly higher with QUANTIPLEX HIV-1 RNA 2.0 than with AMPLICOR HIV-1 MONITOR 1.0. Reanalysis of these results by an ultrasensitive procedure of AMPLICOR HIV-1 MONITOR 1.0 or by a modified version of the test that included additional primers adapted for non-B HIV-1 clades yielded greater differences between the QUANTIPLEX HIV-1 RNA 2.0 assay and the AMPLICOR HIV-1 MONITOR 1.0 assay. Our results indicate that a valid comparison of the virological efficacies obtained with different antiretroviral drug regimens requires the use of the same viral load quantitation procedure; further standardization between the different HIV-1 RNA quantitation kits is therefore needed.     

Theophylline and fibrocystic breast disease

After literature reports linking fibrocystic breast disease (FBD) to methylxanthine ingestion, a pilot study was undertaken to investigate the possible contribution of theophylline to this effect. The major goal of this project was to measure the effect of theophylline therapy on FBD in asthmatic women. All women attending an allergy clinic or an obstetrics/gynecology clinic over a 9-month period were examined to clinically assess FBD and were asked to complete a detailed questionnaire covering health history, other risk factors, and drug and dietary methylxanthines. The sample included 62 asthmatic women, 66 allergic but not asthmatic women, and 72 nonallergic and nonasthmatic women. By use of the FBD clinical taxonomy with its 19-point scale going from 0 to 18 that was developed for this study, the three groups did not differ significantly in terms of mean severity of FBD. On analyzing the effect of each of the methylxanthines on FBD severity, there is clear evidence that total methylxanthines was a contributing factor in FBD severity with or without adjustment for relevant variables, such as age, menopause, pregnancies, and groups. Theophylline was significant only when adjustments were made for age, pregnancy, and menopause in contrast to caffeine that was only significant with no adjustments.     

A PCR–restriction fragment length polymorphism assay to genotype human metapneumovirus

Human metapneumovirus (hMPV) genotypes A and B show epidemiological and probably clinical differences. This report describes a fast and simple PCR–restriction fragment length polymorphism (PCR-RFLP) assay, involving digestion of the fusion protein gene with Tsp 509I, that allows lineages A1, A2, B1 and B2 to be distinguished. The assay should help in elucidating the epidemiology of hMPV, and possibly in predicting the severity of clinical infection.