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Biomedical subjects

J Puel

Publications and source records attributed to J Puel.

At least 55 records · Page 3Linked to original sources
PubMed2001

[Statins and unstable angina: MIRACL].

Statins have demonstrated their aptitude to lower hypercholesterolemia, and to prevent the occurrence of arterial, coronary, and cerebral events, by primary and secondary prevention in patients with low or high risk to develop coronary artery disease. In the first time, with MIRACL and Atrovastatine, statins are proposed in the therapeuty of unstable angina. This study was successful. In fact, in this comparative study, high dose of Atrovastatine (80 mg/day) administrated in the acute phase of non Q-wave myocardial infarction or unstable angina, reduce ischemic events (RR=0.84, p=0.048 ). After anticoagulants and a wide group of platelets antiagregants, this statin brings a new agent to the chemotherapy of the atherosclerotic unstable lesion. The TACTICS-TIMI 18 and the sub-group of the FRISC II study, demonstrate the necessity to stratify the unstable angina risk by electric and biologic arguments. They confirm the efficacy of invasive strategy, with coronarography, and immediate revascularisation, in patients with high risk with persistent modifications of ST segment, and increasing Troponins level. Under the cover of a large medical treatment composed of anti-ischemic, Aspirine, LMWH, and now a high dose of statins, the acute coronary syndrome invasive attitude must be guided by electric, biologic and the invasive attitude prognostic risk.

Angina, Unstable↗
PubMed2001

[The best in 2000 on coronary angioplasty or the postintervention period].

The year 2000 I The left main coronary and myocardial infarction have fallen. The last obstacles confronting the interventional cardiologist have been overcome with the help of stenting. The interventional cardiologist is now working in a limited, well defined functional space and anatomic territory, of which stenting is the main element. It is now known that the successful treatment of arterial stenosis is not necessarily victory over the lesion. The time of conquest and pioneers is over. We are now confronted with the problem of justification of the act by validation of the method and strategies. This is an era of training, organisation and management of the practice with the elaboration and respect of scientific recommendations. Finally, there are new challenges: that of restenosis, and the progression of atherothrombosis, which have led interventional cardiologists to develop: on the one hand, diagnostic tools assessing the arterial lesion just beyond the opacification of the arterial lumen and, on the other hand, therapeutic techniques superseding a mechanical effect on the stenosis. Thus, we are beginning to see the first preventive and curative biological treatments (brachytherapy, gene therapy, anti-atheromatous chemotherapy), founded on a multidisciplinary approach to atheromatous disease.

Angioplasty, Balloon, Coronary↗
PubMed2001

[Small or big].

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Angioplasty, Balloon, Coronary↗
PubMed2001

[Role of HDL cholesterol in the prediction of exercise stress test abnormalities in asymptomatic high-risk patients].

The diagnosis of coronary artery disease in asymptomatic patients is useful in order to target therapeutic intervention in the patients at highest risk. Systematic testing of all asymptomatic adults with coronary risk factors is not feasible. The aim of this study, carried out in 950 healthy subjects, was to assess the predictive value of classical risk factors for positive exercise stress tests (EE). All subjects underwent stress testing using the Bruce protocol. Statistical analysis was performed by multiple logistic regression on half the samples, then by CART (Classification and Regression Trees) analysis on all subjects. Age, HDL-cholesterol and interaction between lipid lowering treatment and LDL-cholesterol were significantly correlated (p < 0.05) to a positive exercise stress test. In both groups, treated or untreated by lipid lowering drugs. CART identified HDL-cholesterol (< 0.40 g/l) as a predictive factor for positive stress testing. Subgroups of elderly patients (> or = 60 years) with probabilities of 20 to 28% for a positive stress test were identified. The authors conclude that the diagnosis of coronary artery disease by systematic exercise stress testing is potentially valuable in elderly patients with low HDL-cholesterol values.

Adult↗
PubMed2000

Shift in HIV resistance genotype after treatment interruption and short-term antiviral effect following a new salvage regimen.

OBJECTIVE: To investigate the changes in genotypic drug-resistance pattern, plasma HIV RNA and CD4 cell count after treatment interruption and assess the short-term antiviral effect of a new salvage regimen. DESIGN: Prospective study of 38 patients with multiple failing regimens who had completely stopped all medication for 3 months before a three to five-drug regimen was reintroduced according to clinical guidelines. METHODS: Patients were tested for HIV resistance before and after treatment interruption by population-based sequencing and clonal analysis of selected patients. RESULTS: Discontinuation of therapy for 3 months was associated with a median increase in HIV RNA of 0.4 log10 and a median decrease in CD4 cell count of 43 x 10(6)/l. Sixty-one per cent of patients had a shift from the drug-resistant genotype to a predominantly wild-type genotype. The patients significantly likely to show genotype reversion were those in Centers for Disease Control groups A or B, who had been exposed to few drugs, had a low plasma HIV RNA, or a high CD4 cell count. The only independent factor predicting genotype reversion was the clinical stage. The median change in plasma HIV RNA at month 3 after treatment reintroduction was -2.3 log10 copies/ml in patients who had genotype reversion compared with -0.6 log10 copies/ml in patients without genotype reversion (P = 0.004). CONCLUSION: Suspending treatment for 3 months after multiple failures could be a suitable strategy for optimizing salvage therapy provided it is instituted early, before the HIV disease becomes too advanced.

Adult↗
PubMed2000

Sperm washing and virus nucleic acid detection to reduce HIV and hepatitis C virus transmission in serodiscordant couples wishing to have children.

BACKGROUND: Use of a motile spermatozoa isolation process was assessed for reducing the transmission of HIV and hepatitis C virus (HCV) during artificial insemination in HIV-serodiscordant couples in which the man is infected. PATIENTS: Thirty-two HIV-1-infected clinically asymptomatic men, having a median CD4 cell count of 396 x 10(6)/l and a median blood plasma HIV-1 RNA content of 414 copies/ml. Of these, 16 were infected with both HIV and HCV. METHODS: Motile spermatozoa were isolated from 51 semen samples by density gradient and 'swim-up'. HIV-1 and HCV genomes were detected and quantified in the blood plasma and seminal plasma, and detected in seminal cell fractions obtained during spermatozoa isolation. RESULTS: HIV-1 RNA was detected in 30% of seminal plasma samples. HIV-1 genomes were found in 18% of seminal cell samples, but in none of the motile spermatozoa fractions after 'swim-up'. There was no correlation between the HIV-1 RNA concentrations in the blood and seminal plasma. HIV-1 genome was detected intermittently in patients who gave more than one sample. HCV RNA was detected in 20% of seminal plasma samples from HCV viraemic patients, but in no seminal cells or motile spermatozoa fractions. CONCLUSIONS: Purification of motile spermatozoa by density gradient plus 'swim-up' reduced the HIV-1 and HCV genomes in the semen of infected individuals to undetectable levels. This method, associated with a standardized virus assay, could be useful for serodiscordant couples (males infected) who wish to have children.

Adult↗
PubMed2000

Carvedilol for prevention of restenosis after directional coronary atherectomy : final results of the European carvedilol atherectomy restenosis (EUROCARE) trial.

BACKGROUND: In addition to its known properties as a competitive, nonselective beta and alpha-1 receptor blocker, carvedilol directly inhibits vascular myocyte migration and proliferation and exerts antioxidant effects that are considerably greater than those of vitamin E or probucol. This provides the basis for an evaluation of carvedilol for the prevention of coronary restenosis. METHODS AND RESULTS: In a prospective, double-blind, randomized, placebo-controlled trial, 25 mg of carvedilol was given twice daily, starting 24 hours before scheduled directional coronary atherectomy and continuing for 5 months after a successful procedure. The primary end point was the minimal luminal diameter as determined during follow-up angiography 26+/-2 weeks after the procedure. Of 406 randomized patients, 377 underwent attempted atherectomy, and in 324 (88.9%), a </=50% diameter stenosis was achieved without the use of a stent. Evaluable follow-up angiography was available in 292 eligible patients (90%). No differences in minimal luminal diameter (1.99+/-0.73 mm versus 2.00+/-0.74 mm), angiographic restenosis rate (23.4% versus 23.9%), target lesion revascularization (16.2 versus 14.5), or event-free survival (79.2% versus 79.7%) between the placebo and carvedilol groups were observed at 7 months. CONCLUSIONS: The maximum recommended daily dose of the antioxidant and beta-blocker carvedilol failed to reduce restenosis after successful atherectomy. These findings are in contrast to those of the Multivitamins and Probucol Trial, which raises doubts regarding the validity of the interpretation that restenosis reduction by probucol was via antioxidant effects. The relationship between antioxidant agents and restenosis remains to be elucidated.

Adrenergic Antagonists↗
PubMed2000

Changes in hepatitis C virus RNA viremia concentrations in long-term renal transplant patients after introduction of mycophenolate mofetil.

BACKGROUND: Mycophenolate mofetil (MMF) is a potent immunosuppressive agent and might inhibit chronic rejection, at least in primates. The prevalence of chronic hepatitis C virus (HCV) infection is high in renal transplant (RT) patients. To date, it has not been demonstrated whether MMF has any effect upon HCV viremia. METHODS: Fourteen long-term HCV(+) RT patients with chronic allograft dysfunction whose maintenance immunosuppression was based on cyclosporine, were given MMF therapy either in place of azathioprine (n=11) or in addition to baseline therapy (n=3). HCV viremia levels were measured by the Amplicor HCV-Monitor RT-PCR assay (Roche Diagnostic Systems) on two separate occasions before the introduction of MMF, and 1 year after changing to MMF or at the last follow-up visit. RESULTS: MMF therapy was associated with a significant rise in HCV viremia, i.e., 5.8+/-0.5 vs. 5.2+/-0.7 log copies/ml (P=0.01), although there were no significant changes in liver enzymes. The increase in HCV viremia was not related to HCV genotypes either. At the patient level, HCV RNA concentrations changed in only seven patients (group B), i.e. >1 log copies/ml, whereas it remained stable in the others (group A). Before conversion, the only significant difference between group A and B was the level of HCV RNA, i.e., 5.5+/-0.4 log copies/ml in group A and 4.9+/-0.7 log copies/ml in group B (P=0.05). CONCLUSION: Our study suggests that MMF should be used with caution in stable HCV RT patients whose maintenance immunosuppressive therapy is based on cyclosporine, at least in the case of patients with a low HCV RNA titer.

Adult↗
PubMed2000

Ten-year clinical and angiographic follow-up of coronary wallstent.

Although stents have been implanted in human coronary arteries since 1986, the long-term angiographic outcome of coronary stenting is unknown. We performed 10-year angiographic follow-up in 8 patients who had undergone stent implantation without acute complications or 6-months' restenosis. Analysis of the changes in minimal luminal diameter within the stent and the reference vessel diameter of the stented segment at 10 years do not suggest that atherosclerosis is accelerated or prolonged beyond 6 months within coronary stents.

Aged↗
PubMed2000

Prevalence of drug resistant mutants and virological response to combination therapy in patients with primary HIV-1 infection.

Baseline genotype resistance analysis was carried out in 48 adults with primary HIV-1 infection between 1995 and 1998 before starting early combination therapy. Seventeen percent (8/48) of the isolates displayed key mutations conferring resistance to reverse transcriptase (RT) inhibitors such as amino acid substitutions 215Y/F (5/48,10%), 70R (3/48, 6%), 184V (2%). Two percent (1/48) had a major mutation associated with resistance to protease inhibitors (D30N). Other mutations at positions 10, 15, 20, 33, 36, 46, 63, 71, 77, 82, 93 of the protease gene were frequent (73%). Among the 46 patients who were given antiretroviral combination therapy and who responded durably to treatment after 6 and 12 months, there was no significant difference between those harboring RT mutant strains (Group I) and those with wild-type isolates (Group II). No significant difference was found at months 6 and 12 between the two groups in terms of CD4+ cell counts. These findings suggest that the presence of drug-resistant strains at the time of primary HIV-1 infection does not necessarily predict drug failure. Other factors, such as adherence to treatment, tolerance and pharmacokinetics parameters are probably major determinants of virological response in patients with early therapeutic intervention.

Adult↗
PubMed2000

Argatroban and alteplase in patients with acute myocardial infarction: the ARGAMI Study.

ARGAMI was designed to assess safety and efficacy of argatroban compared with heparin as adjunctive treatment to alteplase in the treatment of patients with acute myocardial infarction. ARGAMI consisted of an open-dose finding study (35 patients) followed by a placebo-controlled study with double dummy technique and 2:1 (argatroban:heparin) randomization. An argatroban dosage of 100 microg/kg bolus plus 3 microg/kg/min infusion for 72 hours was selected for the randomized study in which 82 patients were allocated to argatroban and 45 to heparin (5000 U intravenous bolus, 1000 U/h infusion). Patency of the infarct-related artery (Thrombolysis in Myocardial Infarction [TIMI] grade 2 or 3 flow) after 90 minutes was obtained in 62 patients (76%) allocated to argatroban versus 37 patients (82%) allocated to heparin (p=ns). Angiograms after 24 hours and 5 to 10 days showed low reocclusion rates in both groups. Bleeding complications were observed in 16 patients allocated to argatroban (19.5%) and in 9 patients allocated to heparin (20.0%). One patient allocated to heparin suffered from hemorrhage stroke. Argatroban, given as adjunctive treatment to alteplase, is tolerated well in patients with acute myocardial infarction. Safety and efficacy of the combination alteplase and argatroban (with this dose regimen) are similar to those of alteplase and heparin.

Aged↗
PubMed2000

Longitudinal analysis of hepatitis C virus replication and liver fibrosis progression in renal transplant recipients.

The pathogenesis of hepatitis C virus (HCV) infection was investigated by analysis of changes in viral and histologic parameters in 36 renal transplant recipients who were infected with HCV before transplantation. Each patient was classified according to development of liver fibrosis as assessed by 2 liver biopsies done 45 and 81 months after transplantation: 13 had progressing liver fibrosis (fibrosers) and 23 did not (nonfibrosers). All developed high-titer posttransplant viremia with a significant increase of 1.2 log RNA copies/mL. There were no significant differences in the increases in serum HCV RNA or genotype distributions in fibrosers and nonfibrosers. The hypervariable region (HVR)-1 of the HCV genome was analyzed by cloning and sequencing 20 clones per sample from 5 fibrosers and 5 nonfibrosers. Comparison of samples revealed that liver fibrosis progression was significantly associated with slower HVR-1 quasispecies diversification, suggesting the selection of more aggressive variants in fibrosers.

Adult↗
PubMed2000

Genetic heterogeneity of hypervariable region 1 of the hepatitis C virus (HCV) genome and sensitivity of HCV to alpha interferon therapy.

Hepatitis C virus (HCV) populations persist in vivo as a mixture of heterogeneous viruses called quasispecies. The relationship between the genetic heterogeneity of these variants and their responses to antiviral treatment remains to be elucidated. We have studied 26 virus strains to determine the influence of hypervariable region 1 (HVR-1) of the HCV genome on the effectiveness of alpha interferon (IFN-alpha) therapy. Following PCR amplification, we cloned and sequenced HVR-1. Pretreatment serum samples from 13 individuals with chronic hepatitis C whose virus was subsequently eradicated by treatment were compared with samples from 13 nonresponders matched according to the major factors known to influence the response, i.e., sex, genotype, and pretreatment serum HCV RNA concentration. The degree of virus variation was assessed by analyzing 20 clones per sample and by calculating nucleotide sequence entropy (complexity) and genetic distances (diversity). Types of mutational changes were also determined by calculating nonsynonymous substitutions per nonsynonymous site (K(a)) and synonymous substitutions per synonymous site (K(s)). The paired-comparison analysis of the nucleotide sequence entropy and genetic distance showed no statistical differences between responders and nonresponders. By contrast, nonsynonymous substitutions were more frequent than synonymous substitutions (P </= 0.05) in responders, but there was no significant difference in nonresponders. Nonsynonymous substitutions tended to be more frequent than synonymous substitutions in women (P = 0.06) but not in men. Nucleotide entropy and genetic distances were significantly related to serum RNA concentration (P </= 0.01). Our findings suggest that after controlling for the major determinants of interferon response, neither complexity nor diversity of the HVR-1 region is associated per se with virus eradication. Because a higher proportion of nonsynonymous substitutions than synonymous substitutions was found only in responders, host anti-HCV-specific immune response rather than viral factors may be playing an important role in the interferon response.

Adult↗