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Biomedical subjects

D Rouleau

Publications and source records attributed to D Rouleau.

At least 19 recordsLinked to original sources
PubMed2000

Comparison of clinical features of acute HIV-1 infection in patients infected sexually or through injection drug use. The Investigators of the Québec Primary HIV Infection Study.

Acute HIV-1 infection (AHI) may present with a clinical picture that represents a diagnostic challenge. We tested the hypothesis that two different routes of infection, that is, sexual versus parenteral, might be associated with a difference in the clinical features of AHI. A prospective cohort of seroconvertors was established in Montréal in private medical clinics and hospitals from February 1996 to May 1999. The prevalence of the symptomatic presentation was almost overlapping within the two groups of newly infected individuals 69% (42 of 61) for men having sex with men (MSM) and 69% (18 of 26) for injection drug users (IDUs; p =.98). Comparison of all types of symptoms and signs as well as their duration was also similar in both groups. Of particular interest, the site of lymph node enlargement was not different despite the estimated sites of intravenous inoculation. Oral and anal ulcers were more frequently observed in MSM than in IDUs (6 versus 0 and 4 versus 1, respectively). Neither the mean CD4+ count (514.8 and 414.7 cells/mm3; p =.14) nor the mean viral load (4.45 and 4.70 log copies/ml; p =.40) were different between the two groups at the time of the first study visit. Our study results clearly indicate that health care workers can expect similar clinical presentation of AHI in MSM and in IDUs despite the different routes of infection.

Adolescent↗
PubMed2000

Comparison of Clinical Features of Acute HIV-1 Infection in Patients Infected Sexually or Through Injection Drug Use.

Acute HIV-1 infection (AHI) may present with a clinical picture that represents a diagnostic challenge. We tested the hypothesis that two different routes of infection, that is, sexual versus parenteral, might be associated with a difference in the clinical features of AHI. A prospective cohort of seroconvertors was established in Montréal in private medical clinics and hospitals from February 1996 to May 1999. The prevalence of the symptomatic presentation was almost overlapping within the two groups of newly infected individuals 69% (42 of 61) for men having sex with men (MSM) and 69% (18 of 26) for injection drug users (IDUs; p =.98). Comparison of all types of symptoms and signs as well as their duration was also similar in both groups. Of particular interest, the site of lymph node enlargement was not different despite the estimated sites of intravenous inoculation. Oral and anal ulcers were more frequently observed in MSM than in IDUs (6 versus 0 and 4 versus 1, respectively). Neither the mean CD4+ count (514.8 and 414.7 cells/mm3; p =.14) nor the mean viral load (4.45 and 4.70 log copies/ml; p =.40) were different between the two groups at the time of the first study visit. Our study results clearly indicate that health care workers can expect similar clinical presentation of AHI in MSM and in IDUs despite the different routes of infection.

Journal Article↗
PubMed2000

Prevalence of HIV-1 resistant to antiretroviral drugs in 81 individuals newly infected by sexual contact or injecting drug use. Investigators of the Quebec Primary Infection Study.

OBJECTIVE: Prolonged treatment with antiretroviral drugs results in the selection of HIV-1 variants with mutations conferring resistance to nucleoside and non-nucleoside reverse transcriptase inhibitors (NRTI and NNRTI) or to protease inhibitors (PI). There is serious concern about transmission of resistant viruses to newly infected persons. This study monitored the prevalence of resistant viruses in individuals undergoing primary HIV infection. DESIGN: Resistance testing was performed on 81 individuals infected between 1997 and 1999 by injecting drug use (n =21), sexual (n = 56), or unknown (n = 4) transmission. METHODS: Automated sequencing was used to genotype the reverse transcriptase (RT) and protease regions of virus isolated from patients' plasma. The phenotypic susceptibility of stimulated peripheral blood mononuclear cells to antiretroviral drugs was assayed. Line probe assays detected quasispecies variations in wild-type and mutated RT codons. RESULTS: A high prevalence of PI and RT genotypic variants, associated with high-level resistance to antiretroviral drugs, was observed in individuals newly infected by injecting drug use (PI = 24%, RT = 24%) or sexual transmission (PI = 12%, RT = 22%). The PI mutations, L101, V82A, and L90M, were found in 10.5, 3 and 4% of cases, respectively; whereas for RT, primary mutations at positions T215Y (zidovudine), M184V (lamivudine), T69D/A (zalcitabine), and K103N (multi-NNRTI) were present in 8, 5, 4, and 4% of subjects, respectively. Resistance to NRTI was demonstrated by phenotypic, genotypic, and line probe analyses. Transmission of multidrug (NRTI/NNRTI/PI) resistance in eight subjects (9.9%) was confirmed by showing that source partners possessed viruses of similar genotype. CONCLUSIONS: The transmission of drug-resistant HIV is a serious problem that merits further attention by public health officials as well as virologists and clinicians.

Anti-HIV Agents↗
PubMed2000

Resistance to antiretroviral drugs in patients with primary HIV-1 infection. Investigators of the Quebec Primary Infection Study.

The widespread use of antiretroviral agents (ARVs) and the growing occurrence of HIV strains resistant to these drugs have given rise to serious concerns regarding the transmission of resistant viruses to newly infected persons. Plasma viral RNA from 80 individuals newly infected between 1997 and 1999 was genotyped by automated sequencing to analyze the profile of viruses resistant to nucleoside and non-nucleoside reverse transcriptase inhibitors (NRTIs and NNRTIs) and to protease inhibitors (PIs). The prevalence of mutations that conferred primary resistance to PIs (L10I, D30Y, V82A, L90M) was 15% of the cohort. RT genotypic variants, associated with high-level resistance to ARVs, were observed in 21% of individuals, including NRTI, NNRTI and multidrug (MDR) resistance in 6, 5, and 10% of cases, respectively. The phenotypic susceptibility of viral isolates to ARVs was also assayed and showed transmission of high-level resistance to ZDV, 3TC, and PIs in those individuals with MDR. The transmission of drug-resistant HIV genotypic variants is a serious problem that merits further attention by public health officials, virologists, and clinicians.

Anti-HIV Agents↗
PubMed2000

Role of hydroxyurea in treatment of disease due to human immunodeficiency virus infection.

The potential role of hydroxyurea in the treatment of human immunodeficiency virus (HIV) infection was first supported by in vitro experiments that demonstrated control of viral production in activated and resting T cells. More recently, controlled clinical trials demonstrated that the addition of hydroxyurea to nucleoside-including regimens (chiefly of didanosine but also of stavudine and lamivudine) enhances their antiviral potency. It is believed that the cytostatic effect of hydroxyurea is at least partially responsible for its antiviral effect, through the down-modulation of cellular proliferation. Such an effect has also been credited for the blunted CD4 T cell responses that are characteristically observed when hydroxyurea is added to nucleoside-including regimens. The adjunctive antiviral effect of hydroxyurea-as well as its favorable dosing schedule, safety profile, and cost-makes it a very attractive addition to our therapeutic armamentarium. Further research is urgently needed to delineate the most appropriate use of this compound in the setting of HIV antiretroviral therapy.

Anti-HIV Agents↗
PubMed2000

Human immunodeficiency virus-infected persons with mutations conferring resistance to zidovudine show reduced virologic responses to hydroxyurea and stavudine-lamivudine.

The baseline predictors of poor virologic response (<0.5 log decrease in plasma virus load) were examined in two 1996 pilot trials of combination nucleoside-analogue therapy. One trial examined the addition of hydroxyurea to didanosine therapy; the other examined stavudine-lamivudine in combination. In both, predictors of virologic response included the presence of mutations associated with zidovudine resistance. For hydroxyurea, the odds ratio (OR) of failure to achieve a short-term (4 weeks) virologic response in a bivariate logistic regression model was 30.8 (95% confidence interval [CI], 1.75-543; P=.02) for use of lower dose hydroxyurea (500 mg/day) and 14.7 (95% CI, 1.1-200; P=.04) for the presence of a zidovudine-related mutation. For the stavudine-lamivudine study, the OR of failure to achieve a virologic response at 4 weeks in a multivariate logistic regression model was 23 (95% CI, 2.7-199; P=.004) for the presence of a mutation at codon 215.

Anti-HIV Agents↗
PubMed1997

Stavudine plus lamivudine in advanced human immunodeficiency virus disease: a short-term pilot study.

The short-term effects of stavudine (d4T) plus lamivudine (3TC) were evaluated among 48 human immunodeficiency virus-infected patients for whom zidovudine therapy had failed or who could not tolerate zidovudine. Patients were followed for 8 weeks after initiation of open-label d4T plus 3TC. Four patients discontinued therapy, because of neutropenia (1), hepatitis (1), or neuropathy (2). Reduction in virus load was -0.86 (+0.3 to -3.4) log10 copies/mL and CD4 cell increase was 30 (-100 to +290) cells/mm3. Virologic response was associated with a higher CD4 cell count, no prior exposure to d4T and 3TC, and no previous AIDS-defining illness. Virus load reduction for patients naive to 3TC and d4T was -1.47 (-0.14 to -3.37) log10 copies/mL. Short-term use of d4T plus 3TC is safe, well-tolerated, and associated with virologic and substantial immunologic benefits. Further evaluation of d4T and 3TC in combination is warranted.

Adult↗
PubMed1996

Summary of track B: clinical science.

AIM: To review Track B on clinical science. Major topics covered were quantitative HIV-1 plasma RNA measurement, combination antiretroviral therapy, protease inhibitors, treatment of primary HIV-1 infection, HIV-1 drug resistance, future use of antiretroviral drugs, paediatric HIV-1 infection, opportunistic infections and HIV/AIDS in developing countries. QUANTITATIVE HIV-1 PLASMA RNA MEASUREMENT: Quantification of HIV-1 RNA is a predictor of progression of immune deficiency and death in HIV-infected adults and children, and is useful in monitoring response to antiretroviral therapy. THERAPY: Combination antiretroviral therapy is now the standard of care, although questions about optimal starting time and the best initial regimen remain unresolved. Protease inhibitors are a powerful new class of antiretroviral agents which in combination with other drugs can produce profound reductions in plasma HIV-1 RNA levels. Trials are in progress of combination antiretroviral therapy, including protease inhibitors, in persons recently infected with HIV-1 to assess the feasibility of permanent suppression or eradication of HIV-1. Adherence to therapy and drug resistance will become increasingly important subjects. CONCLUSIONS: The genuine improvements in patient management are out of reach to the majority of the world's HIV-infected persons, a conclusion with implications which dampened the optimism generated by the conference.

Adult↗
PubMed1983

Activation of adenylate cyclase by beta-adrenergic receptors: investigation of rate limiting steps by simultaneous assay of high affinity agonist binding and GDP release.

We report the development and application of a novel assay for high affinity binding of the agonist [3H]hydrozybenzyl-isoproterenol simultaneously with the agonist-promoted release of membrane bound [32P]GDP in the frog erythrocyte beta-adrenergic receptor system. We find that under various assay conditions both events occur with the same rate, ranging from 0.05 to 0.5 min-1. Addition of the non-hydrolyzable guanine nucleotide, guanylyl-imidodiphosphate simultaneously increases the rate of high affinity agonist binding and agonist promoted GDP release. In addition, the guanine nucleotide analog decreases the steady state level of high affinity agonist binding and increases the steady state level of agonist promoted GDP release with comparable potencies of 0.5 microM and 0.1 microM, respectively. The decrement in the steady state level of high affinity agonist binding (180 fmol/mg protein) due to the guanine nucleotide analog is in the same range as the reciprocal increment in the extent of agonist-induced [32P]GDP release (180 fmol/mg protein). The concommittant activation of adenylate cyclase, by submaximal concentrations of the agonist [3H]hydroxybenzylisoproterenol and guanylylimido-diphosphate under similar assay conditions proceeds with the same rate as for the two other measured functions of the system, i.e. 3H-agonist binding and agonist-promoted [32P]GDP release. This represents the first attempt at comparing the time course of adenylate cyclase activation with that of agonist binding and GDP release under similar assay conditions. The results indicate that GDP is not released prior to but rather coincident with formation of the complex of the hormone receptor with the regulatory protein and that enzyme activation proceeds with the same time course as agonist binds to the receptor. It is concluded that both high affinity agonist binding and GDP release represent integral aspects of the rate limiting step in the enzyme activation mechanism.

Adenylyl Cyclases↗
PubMed1981

Changes in the beta-endorphin content of discrete hypothalamic nuclei during the estrous cycle of the rat.

Concentrations of beta-endorphin were measured in discrete brain nuclei of 4-day cycling rats on each day of the estrous cycle. On the afternoon of proestrus beta-endorphin levels were significantly higher in median eminence and suprachiasmatic nucleus, and lower in arcuate nucleus, when compared to levels found on other days of the cycle. These changes coincided with the peak of plasma prolactin, which was blocked by prior administration of naloxone.

Animals↗
PubMed1981

Regional distributions of somatostatin and cholecystokinin-like immunoreactivities in rat and bovine brain.

The distribution of somatostatin- and cholecystokinin octapeptide (CCK-8)-like immunoreactivities in the central nervous system of bovine and rat has been studied using a sensitive and specific radioimmunoassay. The most interesting information is the high concentration of CCK-8 in the various cortical areas in rat and bovine. The nuclei of amygdala contain the highest amount of octapeptide in rat while in bovine brain, this structure contains the second highest concentration after polus frontalis.

Animals↗
PubMed1981

Inhibition of anterior pituitary prostaglandin-stimulated adenylyl cyclase activity by somatostatin.

Rat anterior pituitary gland adenylyl cyclase activity is stimulated by prostaglandins with an order of potency of PGE1 congruent to PGE2 greater than PGA1 much greater than PGB1 congruent to PGF1 alpha congruent to PGF2 alpha which is the same for cAMP accumulation and growth hormone release. Somatostatin inhibited prostaglandin-stimulated adenylyl cyclase with an ID50 of 1.48 X 10(-8) +/- 0.27 X 10(-8) M. GTP also stimulated adenylyl cyclase activity at concentrations greater than 10(-6) M but did not prevent inhibition by somatostatin. These results indicate that at least one action of somatostatin is exerted directly on cAMP formation.

Adenylyl Cyclases↗