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Biomedical subjects

R L Murphy

Publications and source records attributed to R L Murphy.

At least 37 records · Page 2Linked to original sources
PubMed2000

Development of a low-budget tobacco prevention media campaign.

Utah joined the ranks of other states that have passed a tobacco tax to fund a tobacco control program, including a media campaign. However, unlike other states working with multimillion dollar campaigns, $250,000 was allocated toward an anti-tobacco media campaign. Formative research guided the strategic development of the media campaign.

Adolescent↗
PubMed1999

Safety and antiretroviral effects of combined didanosine and stavudine therapy in HIV-infected individuals with CD4 counts of 200 to 500 cells/mm3.

The safety and antiretroviral effects of didanosine and stavudine in combination were evaluated in 86 people infected with HIV with CD4 counts between 200 and 500 cells/mm3 who had received <7 days of prior nucleoside analogue antiretroviral treatment. Patients were randomized to receive blinded treatments with one of five weight-adjusted, twice-daily regimens of didanosine and stavudine (100 + 10 mg, 100 + 20 mg, 100 + 40 mg, 200 + 20 mg, and 200 + 40 mg) for up to 1 year. Dosages were adjusted appropriately for patients weighing <60 kg and reduced in response to adverse effects. No clear dose-related differences among treatment groups were detected with regard to suppression of plasma HIV RNA level or reduction in infectious titers in peripheral blood mononuclear cells (PBMCs), improvement in CD4 count, or adverse effects. However, trends toward greater decreases in viral load and increases in CD4 count were detected when treatment groups containing the full recommended dosage of one or both agents (high-dose subgroup; arms 3, 4, and 5) were compared with the groups receiving lower dosages. At 28 weeks the mean log 10 HIV RNA decrease was 1.12 (n = 52) and at 52 weeks it was 0.97 (n = 32). Combination therapy was well tolerated, with no apparent dose-related adverse effects. Peripheral neuropathy occurred in 2 of 86 (2.3%) of patients. Didanosine and stavudine together appear to be a good nucleoside analogue foundation for aggressive triple- or quadruple-drug therapy. Full therapeutic doses of each of these two agents should be used to achieve optimal suppression of HIV replication.

Adult↗
PubMed1999

Lamivudine in combination with zidovudine, stavudine, or didanosine in patients with HIV-1 infection. A randomized, double-blind, placebo-controlled trial. National Institute of Allergy and Infectious Disease AIDS Clinical Trials Group Protocol 306 Investigators.

OBJECTIVE: To study the antiviral activity of lamivudine (3TC) plus zidovudine (ZDV), didanosine (ddl), or stavudine (d4T). DESIGN: Randomized, placebo-controlled, partially double-blinded multicenter study. SETTING: Adult AIDS Clinical Trials Units. PATIENTS: Treatment-naive HIV-infected adults with 200-600x10(6) CD4 T lymphocytes/l. INTERVENTIONS: Patients were openly randomized to a d4T or a ddl limb, then randomized in a blinded manner to receive: d4T (80 mg/day), d4T plus 3TC (300 mg/day), or ZDV (600 mg/day) plus 3TC, with matching placebos; or ddl (400 mg/day), ddl plus 3TC (300 mg/day), or ZDV (600 mg/day) plus 3TC, with matching placebos. After 24 weeks 3TC was added for patients assigned to the monotherapy arms. MAIN OUTCOME MEASURE: The reduction in plasma HIV-1 RNA level at weeks 24 and 48. RESULTS: Two hundred ninety-nine patients were enrolled. After 24 weeks the mean reduction in plasma HIV-1 RNA copies/ml from baseline was 0.49 log10 (d4T monotherapy) versus 1.03 log10 (d4T plus 3TC; P = 0.001), and 0.68 log10 (ddl monotherapy) versus 0.82 log10 (ddl plus 3TC; P>0.22). After 48 weeks the mean reduction was 1.08 log10 (d4T plus 3TC) versus 1.01 log10 (ZDV plus 3TC) in the d4T limb (P = 0.66), and 0.94 log10 (ddl plus 3TC) versus 0.88 log10 (ZDV plus 3TC; P = 0.70) in the ddl limb. CONCLUSIONS: 3TC added significantly to the virologic effects of d4T, but not ddl, in treatment-naive patients. 3TC plus d4T produced virologic changes comparable to those of 3TC plus ZDV. These results support the use of 3TC with either ZDV or d4 as a component of initial combination antiretroviral therapy.

Adult↗
PubMed1999

A family history study of male sexual orientation using three independent samples.

Available evidence suggests that male homosexuality is both familial and somewhat heritable and that some cases may be caused by an X-linked gene. However, most studies have recruited subjects in a relatively unsystematic manner, typically via advertisements, and hence suffer from the potential methodological flaw of ascertainment bias due to volunteer self-selection. In the present study we assessed the familiality of male homosexuality using two carefully ascertained samples and attempted to replicate findings consistent with X-linkage in three samples. The percentage of siblings of the probands rated as either homosexual or bisexual, with a high degree of certainty, ranged from 7 to 10% for brothers and 3 to 4% for sisters. These estimates are higher than recent comparable population-based estimates of homosexuality, supporting the importance of familial factors for male homosexuality. Estimates of lambda s for male homosexuality ranged from 3.0 to 4.0. None of the samples showed a significantly greater proportion of maternal than paternal homosexual uncles or homosexual male maternal first cousins. Although our results differed significantly with those of some prior studies, they do not exclude the possibility of moderate X-linkage for male sexual orientation.

Adolescent↗
PubMed1999

Treatment with amprenavir alone or amprenavir with zidovudine and lamivudine in adults with human immunodeficiency virus infection. AIDS Clinical Trials Group 347 Study Team.

Amprenavir is a human immunodeficiency virus (HIV) protease inhibitor with a favorable pharmacokinetic profile and good in vitro activity. Ninety-two lamivudine- and protease inhibitor-naive individuals with >/=50 CD4 cells/mm3 and >/=5000 HIV RNA copies/mL were assigned amprenavir (1200 mg) alone or with zidovudine (300 mg) plus lamivudine (150 mg), all given every 12 h. After a median follow-up of 88 days, the findings of a planned interim review resulted in termination of the amprenavir monotherapy arm. Among 85 subjects with confirmed plasma HIV RNA determination, 15 of 42 monotherapy versus 1 of 43 triple-therapy subjects had an HIV RNA increase above baseline or 1 log10 above nadir (P=.0001). For subjects taking triple therapy at 24 weeks, the median decrease in HIV RNA was 2.04 log10 copies/mL, and 17 (63%) of 27 evaluable subjects had <500 HIV RNA copies/mL. Treatment with amprenavir, zidovudine, and lamivudine together reduced the levels of HIV RNA significantly more than did amprenavir monotherapy.

Adult↗
PubMed1999

Antiviral effect and pharmacokinetic interaction between nevirapine and indinavir in persons infected with human immunodeficiency virus type 1.

Nevirapine and indinavir have the potential of affecting the pharmacokinetics of each other. In a prospective trial, 24 human immunodeficiency virus (HIV)-infected subjects on stable nucleoside or no therapy were treated with 800 mg of indinavir every 8 h. After 7 days, 200 mg of nevirapine a day was added for 14 days and then increased to 200 mg twice a day. At day 7 (before nevirapine), there was a sevenfold difference among the subjects in indinavir area under the curve (AUC), and there was a significant correlation between indinavir AUC (r2=0.378, P=.019), minimum plasma concentration (Cmin; r2=0.359, P=.023), maximum plasma concentration (Cmax; r2=0.340, P=.028), and plasma HIV RNA decline. Nevirapine significantly reduced median indinavir Cmin (47.5%) and AUC (27.4%) and, to a lesser extent, Cmax (11%). Plasma HIV RNA values were </=20 copies/mL in 10 of 17 (58.8%) subjects at 58 weeks or last visit. These data suggest that indinavir dosing should be dependent on drug exposure and not on cotherapy with nevirapine.

Adolescent↗
PubMed1999

Stavudine, lamivudine plus novel protease inhibitor therapy in antiretroviral-naive HIV-infected individuals treated for 24 weeks.

Preliminary results are presented from a dose-comparison trial of the regimen stavudine/lamivudine plus the novel protease inhibitor, ABT-378/ritonavir, given to 101 antiretroviral-naive, human immunodeficiency virus (HIV)-infected subjects for > or = 24 weeks. The HIV-1 RNA had decreased to <400 copies/ml in 94% of patients and CD4 cell count had increased by approximately 160 cells/mm3 at 24 weeks. The regimen was well tolerated and merits further study.

Anti-HIV Agents↗
PubMed1998

Atovaquone compared with dapsone for the prevention of Pneumocystis carinii pneumonia in patients with HIV infection who cannot tolerate trimethoprim, sulfonamides, or both. Community Program for Clinical Research on AIDS and the AIDS Clinical Trials Group.

BACKGROUND: Although trimethoprim-sulfamethoxazole is the drug of choice for the prevention of Pneumocystis carinii pneumonia, many patients cannot tolerate it and must switch to an alternative agent. METHODS: We conducted a multicenter, open-label, randomized trial comparing daily atovaquone (1500-mg suspension) with daily dapsone (100 mg) for the prevention of P. carinii pneumonia among patients infected with the human immunodeficiency virus who could not tolerate trimethoprim-sulfamethoxazole. The median follow-up period was 27 months. RESULTS: Of 1057 patients enrolled, 298 had a history of P. carinii pneumonia. P. carinii pneumonia developed in 122 of 536 patients assigned to atovaquone (15.7 cases per 100 person-years), as compared with 135 of 521 in the dapsone group (18.4 cases per 100 person-years; relative risk for atovaquone vs. dapsone, 0.85; 95 percent confidence interval, 0.67 to 1.09; P=0.20). The relative risk of death was 1.07 (95 percent confidence interval, 0.89 to 1.30; P=0.45), and the relative risk of discontinuation of the assigned medication because of adverse events was 0.94 (95 percent confidence interval, 0.74 to 1.19; P=0.59). Among the 546 patients who were receiving dapsone at base line, the relative risk of discontinuation because of adverse events was 3.78 for atovaquone as compared with dapsone (95 percent confidence interval, 2.37 to 6.01; P<0.001); among those not receiving dapsone at base line, it was 0.42 (95 percent confidence interval, 0.30 to 0.58; P<0.001). CONCLUSIONS: Among patients who cannot tolerate trimethoprim-sulfamethoxazole, atovaquone and dapsone are similarly effective for the prevention of P. carinii pneumonia. Our results support the continuation of dapsone prophylaxis among patients who are already receiving it. However, among those not receiving dapsone, atovaquone is better tolerated and may be the preferred choice for prophylaxis against P. carinii pneumonia.

AIDS-Related Opportunistic Infections↗
PubMed1998

Stavudine-based multiple agent combinations: initial studies and ongoing comparative trials.

Initial studies of multiple-agent antiretroviral combinations including the thymidine nucleoside analogue reverse transcriptase inhibitor (RTI) stavudine (2',3'-didehydro-2',3'-dideoxythymidine; D4T) have shown potent anti-HIV effects in both treatment-naive and -experienced patients. A number of ongoing randomized comparative trials are assessing stavudine-based multiple agent combinations, including protease inhibitor-containing and -sparing regimens, triple nucleoside RTI regimens and regimens including non-nucleoside RTIs and/or hydroxyurea as initial or subsequent therapy. Results of these studies should help to define additional first-line treatment options and strategies for sequencing antiretroviral treatment regimens.

Anti-HIV Agents↗
PubMed1997

A comparative trial of zidovudine administered every four versus every twelve hours for the treatment of advanced HIV disease.

Zidovudine is approved for administration in doses given every 4 hours. Less frequent dosing has been used in many clinical trials, but the toxicity and efficacy of such regimens have not been formally compared with the approved regimen. In this multicenter, randomized, double-blind, controlled trial, the safety, tolerance and efficacy of 600 mg of zidovudine given daily in two or six divided doses were compared. Three hundred and twenty patients with a CD4 lymphocyte count < 250 cells/mm3 (mean, 104 cells/mm3) or a prior AIDS-defining illness were treated with zidovudine 100 mg every 4 hours (regimen A) or 300 mg every 12 hours (regimen B). Eighty-eight patients (56%) and 94 patients (58%), assigned to regimens A and B, respectively, completed the planned 48 weeks of treatment. Serious anemia (hemoglobin < or = 7.5 g/dl) occurred in 13% and 7% of patients treated with regimens A and B, respectively (difference, 6%, 95% confidence interval [CI], 2, 12%; p = .13). The mean duration of treatment and the frequency of neutropenia and symptomatic complaints including nausea and headache were similar in the two treatment groups. The number of patients experiencing a new opportunistic infection (18% versus 20% for regimens A and B, respectively), and the number of deaths (five in each group) did not differ significantly between groups. The effect of treatment on CD4 lymphocyte counts and HIV p24 antigenemia also was similar for both regimens. Zidovudine given at the more convenient dose of 300 mg twice daily has similar safety, and tolerance and appears to have similar efficacy to the currently approved regimen. Use of this regimen should help simplify the treatment of HIV disease.

Adult↗
PubMed1997

The acetate regulatory gene facB of Aspergillus nidulans encodes a Zn(II)2Cys6 transcriptional activator.

Genetic studies have indicated that the facB gene of Aspergillus nidulans is a major regulatory gene involved in acetamide and acetate utilisation. Sequencing of the facB gene revealed that it encodes a protein that contains an N-terminal GAL4-like Zn(II)2Cys6 (or C6 zinc) binuclear cluster for DNA binding, leucine zipper-like heptad repeat motifs and central and C-terminal acidic alpha-helical regions, consistent with a function as a DNA-binding transcriptional activator. The Zn(II)2Cys6 cluster shows strong similarity with those of the Saccharomyces cerevisiae carbon metabolism regulatory proteins CAT8 and SIP4. A significant level of similarity with CAT8 is found throughout the length of the protein, suggesting at least partial functional homology. The facB genes of Aspergillus oryzae and Aspergillus niger were also sequenced and found to be highly conserved. Deletion of the facB gene confirmed that it is required for growth on acetate as a sole carbon source. Functional dissection using deletion and fusion constructs and in vitro mutagenesis indicated that the Zn(II)2Cys6 cluster and the C-terminal end of the protein are required for function.

Acetates↗
PubMed1997

Identification of amdX, a new Cys-2-His-2 (C2H2) zinc-finger gene involved in the regulation of the amdS gene of Aspergillus nidulans.

The acetamidase-encoding amdS gene of Aspergillus nidulans has been shown to be controlled by multiple regulatory genes. A new gene, amdX, involved in amdS regulation was identified during the characterization of a translocation affecting amdS control. The amdX gene is predicted to encode a 1150-amino-acid polypeptide which contains two Cys-2-His-2 (C2H2) zinc finger DNA-binding motifs. Insertional inactivation of amdX and the phenotypes of transformants containing multiple copies of the amdX gene show that it is an activator of amdS expression. A fusion protein containing the AmdX zinc fingers was found to bind to sequences in the 5' region of amdS which overlap binding sites for the CreA and AmdA regulatory proteins. Evidence is presented for AmdX acting at these sites in vivo.

Amino Acid Sequence↗
PubMed1996

The concept of cardioreparation: Part 1. Pathophysiology of remodelling.

PURPOSE: Left ventricular hypertrophy is common in patients with hypertension or congestive heart failure and in survivors of myocardial infarction. It is associated with increased risks of adverse cardiovascular events, including angina, myocardial infarction and congestive heart failure. We aimed to explain these observations in terms of changes in the structure of the heart, collectively described as remodelling. DATA EXTRACTION: Laboratory investigations of animal models of cardiovascular diseases were reviewed. The most prominent features of remodelling are myocyte hypertrophy, excessive accumulation of collagen in the heart (myocardial fibrosis) and pathological changes in the coronary blood vessels. Remodelling disrupts the structure of the heart and impairs its pumping function and blood supply. The reversal of remodelling, termed cardioreparation, could restore cardiac structure and function towards normal and improve the prognosis of patients with cardiovascular diseases. CONCLUSIONS: Cardioreparation implies the regression of myocyte hypertrophy and myocardial fibrosis. Myocyte hypertrophy is primarily a response to chronic pressure or volume overload of the ventricles, whereas myocardial fibrosis depends on activation of circulating and tissue renin-angiotensin-aldosterone systems. Angiotensin converting enzyme inhibitors reduce blood pressure and inhibit these systems. They might therefore induce cardioreparation.

Cardiovascular Diseases↗