Evaluation of viral resistance to reverse transcriptase inhibitors (RTI) in HIV-1-infected patients before and after 6 months of single or double antiretroviral therapy.

We evaluated samples of peripheral blood mononuclear (PBMC) cells from 46 AIDS patients, before starting therapy with HIV-1 reverse transcriptase inhibitors (RTI), and after 6 months of drug use. PBMC were stored and tested by a Line Probe Assay (LiPA), in order to assess the frequency of RT mutations in this population. Six patients were taking AZT before initial blood collection (1 to 16 weeks of drug use) and 40 patients had no prior therapy. After baseline evaluation, 19 patients received AZT, 23 AZT plus DDI, 3 started AZT only with DDI added after 3 months, and 3 received a combination of AZT plus 3TC. Detection of at least one mutation was found in 33% (15/46) of patients at baseline, and 83% (38/46) had at least 1 mutation after 6 months of therapy. In the majority of cases, samples presented with the wild type and variants of HIV, simultaneously. Patients receiving monotherapy had a higher frequency of mutations (L41 and F214, Y215) than did patients receiving double-drug therapy (19 vs. 10). No specific mutation associated with DDI was identified in 26 patients so treated. Despite the finding of a mean increase in CD4 count and a mild decrease in viral load, patients tended to have an inverse correlation between the CD4 variation and number of mutations detected after 6 months, suggesting potential loss of drug efficacy in the presence of these genotypic changes.

Evaluation of carboxymethylcellulose, hydroxypropylmethylcellulose, and aluminum hydroxide as potential carriers for rhBMP-2.

Conventional iliac crest nonvascularized corticocancelous bone grafts and bone flaps have been used to treat bony defects. However, these treatments have some limitations, namely, the availability of donor tissue, donor site morbidity, difficulty to shape the bone flap to the defect, and complexity of the surgery. The bone morphogenetic protein (rhBMP-2) is osteoinductive. However, its implantation requires a matrix (carrier) in order to define the shape of the resulting bone and to retain the protein at the site for the time required for induction to occur. When the ideal carrier is found, an unlimited supply of material would be available for all applications where bone is needed. In this in vitro study, we evaluated the suitability of some potential carriers for rhBMP-2 by measuring the alkaline phosphatase (ALP) activity of fibroblast cultures. Either rhBMP-2 or sodium carboxymethylcellulose significantly increased the ALP activity, when used alone. When sodium carboxymethylcellulose was combined with rhBMP-2, there was an increase in the ALP activity, but lower than those obtained when the products were used alone. Hydroxypropylmethylcellulose alone did not affect ALP activity. However, the combination of rhBMP-2 with hydroxypropylmethylcellulose did not increase the ALP activity, despite the presence of rhBMP-2. Aluminium hydroxide proved to be an unsuitable rhBMP-2 adsorbent.

A randomized, placebo-controlled trial of granulocyte-macrophage colony-stimulating factor and nucleoside analogue therapy in AIDS.

Preliminary preclinical and clinical data suggest that granulocyte-macrophage colony-stimulating factor (GM-CSF) may decrease viral replication. Therefore, 105 individuals with AIDS who were receiving nucleoside analogue therapy were enrolled in a placebo-controlled, double-blind study and were randomized to receive either 125 microgram/m(2) of yeast-derived, GM-CSF (sargramostim) or placebo subcutaneously twice weekly for 6 months. Subjects were evaluated for toxicity and disease progression. A significant decrease in mean virus load (VL) was observed for the GM-CSF treatment group at 6 months (-0.07 log(10) vs. -0.60 log(10); P=.02). More subjects achieved human immunodeficiency virus (HIV)-RNA levels <500 copies/mL at >/=2 evaluations (2% on placebo vs. 11% on GM-CSF; P=.04). Genotypic analysis of 46 subjects demonstrated a lower frequency of zidovudine-resistant mutations among those receiving GM-CSF (80% vs. 50%; P=.04). No difference was observed in the incidence of opportunistic infections (OIs) through 6 months or survival, despite a higher risk for OI among GM-CSF recipients. GM-CSF reduced VL and limited the evolution of zidovudine-resistant genotypes, potentially providing adjunctive therapy in HIV disease.

Human Herpes Virus 8 and Kaposi's Sarcoma: A Review.

Kaposi's Sarcoma (KS) was first described one century ago as a disease occurring in elderly men manifested as an indolent cutaneous form. After the onset of human immunodeficiency virus type I (HIV-1) infection, KS became epidemic which, in association with HIV, presented as an aggressive, systemic disease. Recently, the recognition that a novel human herpes virus-8 (HHV-8) was highly prevalent among KS patients provided strong evidence to indicate that HHV-8 was the etiology of KS. The pathogenesis of KS in AIDS patients is still controversial, but there is evidence suggesting that KS is a cytokine-mediated disease, and that increased levels of inflammatory cytokines in AIDS patients were responsible for the aggressive pattern of the disease seen in such patients. The recently developed serological assays for detection of HHV-8 antibodies have made possible a better understanding of the prevalence of HHV-8 in different populations, and this has allowed a deeper understanding of HHV-8 epidemiology.

[Cardiomyopathy induced by incessant ventricular tachycardia ("tachycardiomyopathy"): cure after control of arrhythmia]. / Miocardiopatia induzida por taquicardia ventricular incessante ("taquicardiomiopatia"). Cura após controle da arritmia.

A case of severe dilated cardiomyopathy in a young boy presenting with incessant ventricular tachycardia, who had been referred for heart transplantation is reported. Complete resolution of dilated cardiomyopathy followed arrhythmia control with oral amiodarone. Such evolution strongly suggests a cause-effect relationship between incessant ventricular tachycardia and dilated cardiomyopathy in this particular case.