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Biomedical subjects

R A Torres

Publications and source records attributed to R A Torres.

At least 19 recordsLinked to original sources
PubMed2001

Trimethoprim-sulfamethoxazole (TMP-SMZ) dose escalation versus direct rechallenge for Pneumocystis Carinii pneumonia prophylaxis in human immunodeficiency virus-infected patients with previous adverse reaction to TMP-SMZ.

Trimethoprim-sulfamethoxazole (TMP-SMZ) is the most effective Pneumocystis carinii pneumonia (PCP) prophylactic agent, but adverse reactions are common among human immunodeficiency virus (HIV)-infected patients and limit its use. This randomized, double-blind controlled trial compared 2 methods of TMP-SMZ reintroduction, 6-day dose escalation and direct rechallenge, for PCP prophylaxis in HIV-infected patients who had experienced previous treatment-limiting reactions. The primary end point was the ability to take single-strength TMP-SMZ daily for 6 months. Seventy-five percent of the dose-escalation group and 57% of the direct-rechallenge group continued to receive daily single-strength TMP-SMZ for 6 months (P= .014). Among premature discontinuations, 58% of the dose-escalation group and 70% of the direct-rechallenge group were due to adverse reactions. None of these reactions was serious. This study provides evidence that it is possible to successfully reintroduce TMP-SMZ to a significant proportion of HIV-infected patients who have experienced mild-to-moderate treatment-limiting adverse reactions.

Adult↗
PubMed2001

Prevalence of CD8(+)alpha beta T cells in Trypanosoma cruzi-elicited myocarditis is associated with acquisition of CD62L(Low)LFA-1(High)VLA-4(High) activation phenotype and expression of IFN-gamma-inducible adhesion and chemoattractant molecules.

The determinants of the prevalence of CD8(+) T cells in the inflamed myocardium of Trypanosoma cruzi-infected patients and experimental animals are undefined. Using C3H/He mice infected with the Colombiana strain of T. cruzi, we found that the distribution of CD4(+)/CD8(-) and CD4(-)/CD8(+) T cells in the myocardium mirrors the frequency of cells expressing the CD62L(Low)LFA-1(High)VLA-4(High) activation phenotype among CD4(+)/CD8(-) and CD4(-)/CD8(+ )peripheral blood T cells. Consistently, vascular cell adhesion molecule-1-positive endothelial cells and a fine fibronectin network surrounding VLA-4(+) mononuclear cells were found in the inflamed myocardium. Further, interferon gamma (IFN-gamma) and IFN-gamma-induced chemokines (RANTES, MIG and CRG-2/IP-10), as well as JE/MCP-1 and MIP1-alpha, were found to be the dominant cytokines expressed in situ during acute and chronic myocarditis elicited by T. cruzi. In contrast, interleukin 4 mRNA was only detected during the chronic phase. Altogether, the results indicate that the distribution of T-cell subsets in the myocardium of T. cruzi-infected mice reflects the particular profile of adhesion molecules acquired by most peripheral CD8(+) T lymphocytes and point to the possibility that multiple IFN-gamma-inducible molecules present in the inflamed tissue contribute to the establishment and maintenance of T. cruzi-induced myocarditis.

Animals↗
PubMed2001

Neuroleptic malignant syndrome during a change from haloperidol to risperidone.

OBJECTIVE: To report a case of neuroleptic malignant syndrome (NMS) in a patient whose therapy was being switched from haloperidol to risperidone. CASE REPORT: A 57-year-old African-American man, treated for schizophrenia with haloperidol for several years, developed NMS within 48 hours of the addition of low doses of risperidone and mirtazapine to his regimen. Symptoms, which included fever, generalized rigidity, and altered mental status, resolved after discontinuation of psychotropics, supportive management, and several weeks of treatment with bromocriptine and dantrolene. He was subsequently treated with olanzapine without adverse effects. DISCUSSION: Several cases of NMS have been reported with risperidone, but none under these circumstances. NMS most likely occurred in this patient as a result of the additive dopamine 2 receptor blocking of haloperidol and risperidone. Sympathetic hyperactivity secondary to mirtazapine may also have been a contributing factor. If NMS may be induced by the simultaneous use of older, high-potency antipsychotics and newer, atypical antipsychotics such as risperidone, switching patients from older to newer antipsychotics may at times be difficult, since completely stopping one antipsychotic before starting the second may place patients at risk for psychotic relapse. CONCLUSIONS: Clinicians should closely monitor patients receiving both haloperidol and risperidone or combinations of similar medications.

Antipsychotic Agents↗
PubMed2000

A randomized study of the safety and antiretroviral activity of hydroxyurea combined with didanosine in persons infected with human immunodeficiency virus type 1. American Foundation for AIDS Research Community-Based Clinical Trials Network.

This randomized open-label trial of human immunodeficiency virus type 1-infected persons compared safety and efficacy for 38 patients receiving hydroxyurea/didanosine combination therapy with findings in 42 persons given didanosine monotherapy for 12 weeks, followed by 12 weeks of hydroxyurea/didanosine combination therapy for all patients. Week 12 on-treatment group comparisons showed a mean decrease in virus load between hydroxyurea/didanosine versus didanosine groups of -0.93 versus -0.74 log10 copies/mL (P=.20); a higher percentage of the hydroxyurea/didanosine group below the assay's detection limit (500 copies/mL), 29% versus 7% (P=.017); and median change in CD4 cells for the hydroxyurea/didanosine versus didanosine group of 0 versus 43 cells/mm3 (P=.045), although median change in CD4 percentage was similar (0.9% vs. 1.2%, P=.64). Week 24 virus load reductions and CD4 cell changes were similar in both groups. Intent-to-treat and on-treatment analyses showed similar results. The hydroxyurea/didanosine combination was well tolerated.

Adult↗
PubMed1999

Theoretical investigation of the [1,2]-sigmatropic hydrogen migration in the mechanism of oxidation of 2-aminobenzoyl-CoA by 2-aminobenzoyl-CoA monooxygenase/reductase.

The flavin hydroperoxide at the active site of the mixed-function oxidase 2-aminobenzoyl-CoA monooxygenase/reductase (Azoarcus evansii) transfers an oxygen to the 5-position of the 2-aminobenzoyl-CoA substrate to provide the alkoxide intermediate II(-). Hydrogen migration from C5 to C6 follows this monooxygenation. The nature of the monooxygenation intermediate and plausible competing reactions leading to hydrogen migration have been considered. Ab initio molecular orbital theory has been used to calculate structures and electron distributions in intermediate and transition state structures. Electrostatic potential surface calculations establish that the transition state and product, associated with the C5 to C6 hydrogen transfer, are stabilized by electron distribution to the benzoyl-CoA thioester carbonyl oxygen. This is not so for the transition state and product associated with hydrogen transfer from C5 to C4. The activation energy for the 5, 6-shift is 2.5 kcal/mol lower than that for the 5,4-shift. In addition, the product of the hydrogen 5,6-shift is more stable than is the product of the hydrogen 5,4-shift, by approximately 6 kcal/mol. These results explain why only the shift of hydrogen from C5 to C6 is observed experimentally. Oxygen transfer and hydrogen migration almost coincide in the gas phase (activation energy of approximately 0.6 kcal/mol, equivalent to a single bond vibration). Enzymatic formation of alkoxide II(-) requires its stabilization; thus, the rate constant for its breakdown would be slower than in the gas phase.

Acyl Coenzyme A↗
PubMed1999

Altered body shape in HIV disease: a side effect of therapy?

An interactive teleconference on HIV-associated lipodystrophies and altered body habitus was held on January 20, 1999, part of a series known as HIV Treatment LIVE!. It was moderated by Ronald Baker, Ph.D., and sponsored by the AIDS Wasting Foundation (AWF). AWF, located at 15 East 26th Street, New York, NY 10010, was founded in 1997 as an education and advocacy organization, under the direction of Carola Burroughs, Executive Director. This tele-conference brought together three AIDS experts to address important issues concerning the etiology, diagnosis, and treatment of this novel and enigmatic syndrome. The resulting report is an edited, selected transcript of that discussion.

Anti-HIV Agents↗
PubMed1998

Antiretroviral effect and safety of abacavir alone and in combination with zidovudine in HIV-infected adults. Abacavir Phase 2 Clinical Team.

OBJECTIVES: To evaluate, over 12 weeks, the antiretroviral activity and safety of abacavir, used alone and in combination with zidovudine (ZDV), as treatment for HIV-1-infected subjects who had limited or no antiretroviral treatment. DESIGN: Seventy-nine HIV-1-infected subjects, with CD4 cell counts 200-500 x 10(6)/l and <12 weeks of previous treatment with ZDV were enrolled in a multicenter study. Subjects were randomly assigned to one of four cohorts receiving abacavir monotherapy for the first 4 weeks (200, 400, or 600 mg every 8 h daily, or 300 mg every 12 h daily) and, thereafter, combination therapy of abacavir with 600 mg ZDV or ZDV placebo, administered in a double-blind manner for an additional 8 weeks. METHODS: Antiretroviral activity was assessed by measuring changes in plasma HIV-1 RNA levels and CD4+ cell counts. Safety was assessed by monitoring clinical adverse events and laboratory abnormalities during the 12-week period and for 4 weeks post-treatment. RESULTS: Treatment with abacavir, alone or in combination with ZDV, produced marked decreases in plasma HIV-1 RNA loads and increases in CD4+ cell counts in all groups. At week 4, median plasma HIV-1 RNA loads decreased by 1.11-1.77 log10 copies/ml and median CD4+ cell counts increased by 63-111 x 10(6)/l in all groups. At week 12, median HIV-1 RNA loads decreased by 1.02-2.24 log10 copies/ml (abacavir monotherapy) and by 1.81-2.01 log10 copies/ml (abacavir-ZDV); median CD4+ cell counts increased by 79-195 x 10(6)/l (abacavir monotherapy) and by 93-142 x 10(6)/l (abacavir-ZDV). At week 12, the percentage of subjects who had plasma HIV-1 RNA levels below 400 and 40 copies/ml were 28 and 11%, respectively (abacavir monotherapy) and 69 and 22%, respectively (abacavir-ZDV). Eight subjects (10%) discontinued the study prematurely because of adverse events; nausea (n = 4) and hypersensitivity (n = 3) were the most common reasons for withdrawal. There were no deaths among the study subjects. CONCLUSIONS: In HIV-infected subjects who have received little or no prior antiretroviral therapy, treatment with abacavir alone or in combination with ZDV is well tolerated and resulted in sustained improvements in key immunologic and virologic efficacy parameters through 12 weeks.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Molecular dynamics study displays near in-line attack conformations in the hammerhead ribozyme self-cleavage reaction.

We have performed molecular dynamics (MD) calculations by using one of the recently solved crystal structures of a hammerhead ribozyme. By rotating the alpha, beta, gamma, delta, epsilon, and zeta torsion angles of the phosphate linkage of residue 17, the nucleobase at the cleavage site was slightly rotated out of the active site toward the solution. Unconstrained MD simulations exceeding 1 ns were performed on this starting structure solvated in water with explicit counter ions and two Mg2+ ions at the active site. Our results reveal that near attack conformations consistently were formed in the simulation. These near attack conformations are characterized by assumption of the 2'-hydroxyl to a near in-line position for attack on the -O-(PO2-)-O- phosphorous. Also during the time course of the MD study, one Mg2+ moved immediately to associate with a pro-R phosphate oxygen in the conserved core region, and the second Mg2+ remained associated with the pro-R oxygen on the phosphate linkage undergoing hydrolysis. These results are in accord with a one-metal ion mechanism of catalysis and give insight into the possible roles of many of the conserved residues in the ribozyme.

Binding Sites↗
PubMed1998

Activity of the soft gelatin formulation of saquinavir in combination therapy in antiretroviral-naive patients. NV15355 Study Team.

OBJECTIVE: A Phase II, open-label, randomized, parallel-arm, multicentre trial to compare the antiviral activity and safety of two formulations of saquinavir (SQV), soft gelatin (SQV-SGC) and hard gelatin (SQV-HGC) capsules, in combination with two nucleoside reverse transcriptase inhibitors (NRTI), in antiretroviral-naive, HIV-1-infected individuals. PARTICIPANTS: A total of 171 people of > or = 13 years, with plasma HIV-1 RNA levels > or = 5000 copies/ml, who had received no protease inhibitor therapy, < or = 4 weeks NRTI therapy and no antiretroviral treatment within 28 days of screening. Eighty-one people were randomized to the SQV-HGC group and 90 to the SQV-SGC group. A total of 148 patients completed 16 weeks of therapy. INTERVENTION: Therapy for 16 weeks with either SQV-SGC 1200 mg or SQV-HGC 600 mg, both three times a day, in combination with two NRTI. RESULTS: Using an on-treatment analysis, patients taking SQV-SGC had a larger reduction in plasma HIV-1 RNA than those taking SQV-HGC (-2.0 versus -1.6 log10 copies/ml). Eighty per cent of those on SQV-SGC had < 400 copies HIV RNA/ml, compared with 43% in the SQV-HGC group (P = 0.001). A statistically significant difference in the area under the curve (AUC) values between the SQV-SGC and SQV-HGC arms (-1.7 versus -1.5 log10 copies/ml, respectively; P = 0.0054) was observed when withdrawals prior to week 12, major protocol violators and patients with < 75% compliance were excluded from the analysis; however, the difference between the values for the intent-to-treat population was not significant (P = 0.1929). Adverse events (mostly mild) included diarrhoea and nausea. CONCLUSIONS: SQV-SGC was generally well tolerated and gave significantly more potent suppression of plasma HIV-1 RNA in antiretroviral-naive patients than SQVHGC.

Adolescent↗
PubMed1998

A randomized, placebo-controlled trial of the safety and efficacy of oral ganciclovir for prophylaxis of cytomegalovirus disease in HIV-infected individuals. Terry Beirn Community Programs for Clinical Research on AIDS.

OBJECTIVE: Evaluate safety and efficacy of oral ganciclovir (GCV) for preventing cytomegalovirus (CMV) disease in HIV-infected persons at high risk for CMV disease. DESIGN: Double-blind, placebo-controlled, randomized clinical trial in primary care clinics and private practice offices specializing in the care of people with HIV. Interventions were oral GCV (1000 mg three times/day) or placebo. Protocol amendment allowed switch to open-label oral GCV. Main outcome measures were confirmed CMV retinal or gastrointestinal mucosal disease, and death. The study enrolled 994 people co-infected with CMV and HIV, with at least one CD4 count recorded < 100 x 10(6) cells/l. RESULTS: At study completion (15 months median follow-up), CMV event rates in the oral GCV and control groups were 13.1 and 14.6 per 100 person years, respectively, a hazard ratio (HR) of 0.92 [95% confidence interval (CI), 0.65-1.27; P = 0.6]. At protocol amendment event rates were 12.7 and 15.0, respectively (HR, 0.85; 95% CI, 0.56-1.30; P = 0.45). At study completion, event rates for death were 26.6 and 32.0 (HR, 0.84; P = 0.09), and at protocol amendment were 18.9 and 19.6 (HR, 0.95; P = 0.78), respectively. At protocol amendment for the CMV endpoint, the oral GCV treatment effect was associated with baseline use of didanosine (ddI). For patients taking ddI at randomization, HR was 7.48 (P = 0.02). For patients not taking ddI, HR was 0.62 (P = 0.04). These HR were statistically different (P = 0.0006). CONCLUSIONS: In our study, 3 g/day oral GCV did not significantly reduce CMV disease incidence, but there was a suggestion of a death-rate reduction. Furthermore, results suggest that oral GVC decreased risk of CMV disease in patients not prescribed ddI, and increased risk in those prescribed ddI. For the CMV endpoint, our study differs markedly from the only similar study, although for the death endpoint, a combined analysis of studies indicated significant reduction in death rate.

AIDS-Related Opportunistic Infections↗
PubMed1998

Acyclovir use and survival among human immunodeficiency virus-infected patients with CD4 cell counts of < 500/mm3. The Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA).

To examine the relationship between acyclovir use and survival in AIDS, we performed a retrospective analysis of data collected through an observational cohort of the 17-site Community Program for Clinical Research on AIDS (CPCRA), under the sponsorship of the National Institute of Allergy and Infectious Diseases. Data were analyzed regarding 2,368 patients with CD4+ lymphocyte counts of < 500/mm3, and 7,836 follow-up visits were conducted from September 1990 to July 1994. Factors associated with use of acyclovir were studied by stratified analysis of variance and Mantel-Haenzel chi 2 tests. The association between acyclovir and survival was studied with use of the proportional hazards regression model. Individuals reporting acyclovir use were more likely to be white, male, and homosexual; to have a history of herpes simplex and zoster; and to have lower CD4+ T cell counts than those who did not. After adjustments for differences in baseline factors, acyclovir use was not associated with prolonged survival.

Acyclovir↗
PubMed1998

Rates of tuberculosis infection in healthcare workers providing services to HIV-infected populations. Terry Beirn Community Programs for Clinical Research on AIDS.

OBJECTIVE: To assess the prevalence of tuberculosis (TB) or a positive skin test in healthcare workers (HCWs) providing services to human immunodeficiency virus (HIV)-infected individuals and to determine prospectively the incidence of new infections in this population. DESIGN: This prospective cohort study enrolled 1,014 HCWs working with HIV-infected populations from 10 metropolitan areas. Purified protein derivative (PPD) tuberculin skin tests were placed at baseline and every 6 months afterwards on those without a history of TB or a positive PPD. Demographic, occupational, and TB exposure data also were collected. SETTING: Outpatient clinics, hospitals, private practice offices, and drug treatment programs providing HIV-related healthcare and research programs. PARTICIPANTS: A voluntary sample of staff and volunteers from 16 Community Programs for Clinical Research on AIDS units. RESULTS: Factors related to prior TB or a positive skin test at baseline included being foreign-born, increased length of time in health care, living in New York City, or previous bacille Calmette-Guerin vaccination. The rate of PPD conversion was 1.8 per 100 person years of follow-up. No independent relation was found between the amount or type of contact with HIV-infected populations and the risk of TB infection. CONCLUSION: These data provide some reassurance that caring for HIV-infected patients is not related to an increased rate of TB infection among HCWs in these settings.

AIDS-Related Opportunistic Infections↗
PubMed1997

Atovaquone for salvage treatment and suppression of toxoplasmic encephalitis in patients with AIDS. Atovaquone/Toxoplasmic Encephalitis Study Group.

To examine the efficacy of atovaquone as salvage therapy in patients with AIDS-related toxoplasmic encephalitis, 93 patients with AIDS and toxoplasmic encephalitis who were intolerant of standard therapy (pyrimethamine plus sulfadiazine or clindamycin) or for whom such therapy was failing were treated with atovaquone tablets (750 mg four times daily) for 18 weeks. Plasma levels of atovaquone were measured with high-pressure liquid chromatography, and the clinical and radiological responses and survival were compared according to median plasma concentration groups. During the acute-therapy phase (the first 6 weeks), the conditions of 52% and 37% of the patients, respectively, were clinically or radiologically improved; the conditions of 26% and 15% remained clinically or radiologically improved by week 18. Median survival for all patients was 189 days (Kaplan-Meier estimate). A post-hoc analysis revealed a positive relationship between clinical and radiological responses and median atovaquone plasma concentrations. Survival time among patients with high or medium median steady-state plasma concentrations (319 and 289 days) was significantly better than that among those with low plasma concentrations (114 days; P = .003 and P = .006, respectively).

AIDS-Related Opportunistic Infections↗
PubMed1996

Randomised trial of MNrgp120 HIV-1 vaccine in symptomless HIV-1 infection.

BACKGROUND: Most individuals infected with HIV-1 show disease progression despite both cellular and humoral immune responses. We investigated whether immunisation of patients who had symptomless HIV-1 infection with an envelope subcomponent vaccine (MNrgp120) to augment immune response can slow progression of HIV-1 disease. METHODS: In a randomised, double-blind, placebo-controlled trial, carried out in university infectious disease clinics and community infectious disease practices, we enrolled 573 HIV-infected patients with CD4 counts above 600 cells/microL (0.6 x 10(9)/L). Patients received 600 micrograms vaccine or placebo by intramuscular injection monthly for 6 months then every alternate month throughout the study. The primary endpoint was the rate of decline in CD4 count; secondary endpoints were HIV-1 RNA concentrations in plasma and minor clinical events associated with HIV. Analysis was by intention to treat. FINDINGS: At baseline, the study participants had a mean CD4 count of 775 cells/microL (SD 172) and 89% of participants had detectable HIV RNA (> 200 copies/mL). These RNA-positive individuals had a median viral load of 9250 copies/mL (IQR 2670-26960). Analysis after 15 months of follow-up of the 568 subjects who had at least one CD4 count done after randomisation showed no difference between the 287 vaccine recipients and 281 placebo recipients in rate of decline of CD4 count (yearly decrease 53.8 [SE 7.6] vs 42.3 [7.6] cells/microL; ratio of mean gradients 1.27 [95% CI 0.63-2.55]) or in plasma HIV-1 RNA concentrations (p > or = 0.63). The study was designed with power to detect a vaccine-induced reduction in rate of decline in CD4 count of 60%; these results exclude with 95% confidence a reduction of 40% or more. More vaccine-treated patients than placebo recipients showed a 50% decrease in CD4 count (11 vs 5; relative risk 2.15 [95% CI 0.76-6.12], p = 0.13). The frequencies of HIV-related minor clinical events were similar in the two groups. Pain at the injection site was the only adverse event that occurred more frequently in vaccine-treated group. INTERPRETATION: Postinfection immunisation of symptom-free HIV-infected patients with MNrgp120 vaccine did not alter HIV-1 disease progression as measured by immunological, virological, and clinical endpoints over a 15-month period.

AIDS Vaccines↗
PubMed1996

Molecular mechanics calculations of the riboacetal internucleotide linkage in double and triple helices.

Structures of Watson-Crick base paired 15-nucleobase oligomer strands in A-type or B-type conformation in which one strand [a strand of alternating nucleotide and riboacetal thymidine nucleoside (RT) units, RP] is DNA and the other is composed of alternating nucleotides and riboacetal nucleosides have been studied by molecular mechanics. Analogously, oligomer strands of RNA in place of DNA have been modeled. The calculations indicate that the RP strand is more stable when complexed in an A-type duplex relative to a B-type form and that this conformational preference is presumably due to the more uniform nature of the former. Nearly planar ribose rings were more commonly observed in the minimized structures of the B-type DNA.RP duplexes as compared with A-type duplexes, despite the fact that planar ribofuranose rings are known to be energetically unfavorable in oligonucleotides. Computed relative stabilities of all duplexes containing the RP strand suggest that such heteroduplexes are less stable than the corresponding double-stranded DNA and double-stranded RNA species. These findings are in agreement with experimental results which show, when equivalent sequences were compared, that a DNA.RNA control forms a more stable duplex than RP hound to a complementary single-stranded RNA strand. In contrast, molecular mechanics studies of complementary triple-helical (DNA)2.RP, (DNA)2.DNA, and (DNA)2.RNA structures indicate that the binding of RP as a Hoogsteen strand stabilizes the underlying duplex to a greater extent compared with native oligonucleotides. These calculations suggest that puckering of the ribose ring in the riboacetal linkage leads to a more favorable interaction with a complementary nucleic acid target than the proposed planar geometry and that this puckering may account for the enhanced binding of RP to a double-stranded target.

Acetals↗