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Biomedical subjects

H Portier

Publications and source records attributed to H Portier.

At least 37 records · Page 2Linked to original sources
PubMed2001

Coronary heart disease associated with the use of human immunodeficiency virus (HIV)-1 protease inhibitors: report of four cases and review.

Four cases of human immunodeficiency virus (HIV)-infected patients who developed coronary heart disease (CHD) while under treatment with a protease inhibitor (PI) are described, and the epidemiologic and clinical features of 18 cases reported in the literature are analyzed. Cardiac manifestations mostly included myocardial infarctions. Smoking and hyperlipidemia were the most common risk factors for CHD, reported in 72 and 81% of the patients, respectively. Hypercholesterolemia was observed in 75% of the cases at the time of the cardiovascular event. Ninety percent of the patients with pretreatment normal lipid values experienced a rise in the plasma lipid levels during PI therapy. Although a definite relationship between the development of CHD and HIV PIs can not be made, this analysis suggests that PI-induced hyperlipidemia may play a role in accelerating coronary atherosclerosis in patients with concomitant risk factors. Evaluation and control of risk factors for CHD should be performed in each patient for whom treatment with a PI is indicated.

Adolescent↗
PubMed2001

Effects of aerobatics flight on oxygen consumption and heart rate control: influence on autonomic cardiovascular regulation during recovery.

Oxygen consumption (VO2) and blood pressure regulation were measured on five pilots during and after normal training aerobatics flights of a mean duration of 35 min. The acceleration vector along the longitudinal axis of the body (Gz) ranged from + 6.5 Gz to -3.5 Gz. VO2 was continuously monitored by a miniature telemetric system (K2). Heart rate (fc), the abdominal muscle electromyogram (EMG) and Gz levels were recorded synchronously on a magnetic tape recorder. A tilt test was performed pre- and post-flight to evaluate fc and blood-pressure variability. The left forearm blood flow was measured by strain-gauge plethysmography. The mean VO2 during flight was 1.2 l x min(-1), with a peak VO2 of 2.1 l x min x fc ranged between 55 and 165 beats x min(-1) and showed a progressive increase under the effect of + Gz, with a sudden fall during -Gz. The abdominal muscle EMG indicated the occurrence of muscle contraction under Gz load. Maximal responses were observed during the Gz phase. Comparison between pre- and post-flight data showed lower post-flight systolic blood pressure with higher fc. Before flight, upright tilt induced a significant increase in low/ high frequency fc, as assessed using spectral analysis. This change was suppressed after flight. In summary, these data show that aerobatics flight leads to enhanced energy expenditure, mainly because of increased skeletal muscle work. The post-flight tilt test showed that aerobatic flight favors parasympathetic drive and, consequently, modifies blood pressure regulation during recovery. This action may decrease + Gz tolerance to a second aerobatics flight performed shortly after the first.

Abdominal Muscles↗
PubMed2001

[Treatment of acute group A beta-hemolytic streptococcal tonsillitis in children with a 5-day course of josamycin].

MATERIAL AND METHODS: In this randomized open study, 325 children aged two to 15 years with acute tonsillitis and a positive test of GA beta H streptococcal antigen were treated with josamycin 50 mg.kg-1.day-1 b.i.d for 5 days, or penicillin 50,000 to 100,000 IU/day t.i.d for 10 days. Clinical assessments and throat cultures for GA beta HS isolation were performed at the inclusion visit (V1), at the end of treatment visit (V2: day 12 for all patients) and at the follow-up visit (V3: day 30). In case of positive GA beta HS culture, the bacterial DNA by RFLP was performed to differentiate between the persistence (presence of original strain at V2), relapse (eradication at V2 and acquisition of same strain at V3) and reinfection (eradication at V2 and acquisition of different strain at V3). RESULTS: Two hundred and twenty-three patients were included in the bacteriological and clinical criteria per protocol analysis. At V2, eradication rates were comparable: 82% in josamycin and 80% in penicillin patients; clinical cure rates were 90% and 89%. At V3, relapse of GAS assessed only on clinically and bacteriologically cured patients at V2 occurred in 12% of josamycin patients and 12.8% of penicillin patients. Tolerance was good; 14% and 10% of josamycin and penicillin patients respectively experienced an adverse event. CONCLUSION: In this non-inferiority study, the efficacy of a 5-day course of josamycin is comparable to reference treatment in GA beta HS tonsillitis in children.

Acute Disease↗
PubMed2001

HMR 3647 human-like treatment of experimental pneumonia due to penicillin-resistant and erythromycin-resistant Streptococcus pneumoniae.

An experimental Streptococcus pneumoniae pneumonia model in rabbits was used to assess the efficacy of amoxycillin, erythromycin and a new ketolide, telithromycin (HMR 3647). The MICs of amoxycillin, erythromycin and HMR 3647 for the three clinical S. pneumoniae strains used were, respectively, (mg/L): 0.01, 16 and 0.02 (strain 195); 2, 0.25 and 0.02 (strain 16089); 8, >64 and 0.02 (strain 11724). Antibiotic therapy reproduced human serum pharmacokinetics (amoxycillin 1 g iv tds or erythromycin 500 mg qds or HMR 3647 800 mg bd). Forty-eight hours of therapy with HMR 3647 and amoxycillin resulted in significant bacterial clearance in the lungs and spleen of rabbits infected by S. pneumoniae strain 195 and strain 16089 (at least 3 log(10) cfu/g decrease, P < 0.001). Erythromycin was active against only the erythromycinsusceptible strain (3 log(10) cfu/g decrease at 48 h, P < 0.001). None of the antibiotics showed significant efficacy with strain 11724. All agents produced significant bacterial clearance when time above MBC was >33%, and microbiological failure when it was <25%, whereas MIC was not correlated with microbiological outcome with HMR 3647. Our findings suggest that pharmacodynamic data integrating MBC may be predictive of microbiological success or failure with greater accuracy than with MIC. HMR 3647 produced significant bacterial clearance in both penicillin- and erythromycin-resistant pneumonia, but was less effective against the highly erythromycin-resistant S. pneumoniae strain.

Amoxicillin↗
PubMed2001

Genetic and phenotypic characterization of macrolide resistance in group A streptococci isolated from adults with pharyngo-tonsillitis in France.

Three hundred and three strains of group A streptococci (GAS) isolated from adults with pharyngitis were tested to evaluate their phenotype of resistance to macrolides-lincosamides and to search for macrolide resistance genes. MICs of clarithromycin were determined. The overall rate of resistance to both erythromycin and clarithromycin was 9.6%. Constitutive, inducible and M phenotypes of resistance were detected in 4.3, 2 and 3.3% of strains, respectively. All constitutive phenotypes harboured ermB genes, whereas inducible phenotypes had the ermTR gene and M phenotypes had the mefA gene. In France, the current resistance rate of GAS to erythromycin and clarithromycin remains low.

Adenoids↗
PubMed2001

Intense endurance training on heart rate and blood pressure variability in runners.

UNLABELLED: Physical training with incomplete recovery times can produce significant fatigue. A study of cardiovascular responses showed that there is a sympathetic and a parasympathetic form of fatigue. PURPOSE: The purpose of this experimentation was to measure the effects of intense endurance training on autonomic balance through a spectral analysis study of the heart rate (HR) and systolic blood pressure (SBP). METHODS: Eight elite runners were tested twice: after a relative rest period (RRP) of 3 wk and after an 12-wk intense training period (ITP) for endurance. At the end of each phase, the subjects were tested by means of a VO2max test and a tilt-table test. RESULTS: The resting heart rate (HR) variability was lower (P < 0.001) in the intensive training phase. Likewise, there were differences in the low-frequency (0.04-0.150 Hz; LF) and high-frequency (0.150-0.500 Hz; HF) components and the LF/HF ratio of the HR spectral analysis. The LF spectral power was significantly lower in the supine position (P < 0.05) during ITP. Upright tilting was accompanied by a 22.6% reduction in HF values during the rest period, whereas in ITP the HF spectral power rose by 31.2% (P < 0.01) during tilt, characterizing a greater parasympathetic system control. Sympathetic control represented by the LF/HF ratio regressed markedly (P < 0.01) in response to the tilt test in ITP. CONCLUSIONS: The spectral analysis of SBP in the high frequencies shows that the changes in cardiac parameters are coupled with a decrease in sympathetic vasomotor control (-18%) and a reduction in diastolic pressure (-3.2%) in the response to the tilt test at the end of ITP. Spectral analysis could be a means of demonstrating impairment of autonomic balance for the purpose of detecting a state of fatigue that could result in overtraining.

Adult↗
PubMed2001

Fractional maximal effect method for in vitro synergy between amoxicillin and ceftriaxone and between vancomycin and ceftriaxone against Enterococcus faecalis and penicillin-resistant Streptococcus pneumoniae.

In the present study we assessed the use of a new in vitro testing method and graphical representation of the results to investigate the potential effectiveness of combinations of amoxicillin (AMZ) plus ceftriaxone (CRO) and of CRO plus vancomycin (VAN) against strains of Streptococcus pneumoniae highly resistant to penicillin and cephalosporins (PRP strains). We used the fractional maximal effect (FME) method of time-kill curves to calculate adequate concentrations of the drugs to be tested rather than relying on arbitrary choices. The concentrations obtained, each of which corresponded to a fraction of the maximal effect, were tested alone and in combination with the bacterial strains in a broth medium. Synergy was defined as a ratio of observed effect/theoretical effect, called FME, of greater than 1, additivity was defined as an FME equal to 1, and antagonism was defined as an observed effect lower than the best effect of one of the antibiotics used alone. The area between antagonism and additivity is the indifference zone. The well-known synergy between amoxicillin and gentamicin against a reference strain of Enterococcus faecalis was confirmed, with a best FME equal to 1.07. Two strains of PRP, strains PRP-1 and PRP-2, were studied. The MICs for PRP-1 and PRP-2 were as follows: penicillin, 4 and 16 microg/ml, respectively; AMZ, 2 and 8 microg/ml, respectively, CRO, 1 and 4 microg/ml, respectively; and VAN, 0.5 and 0.25 microg/ml, respectively. For PRP-1 the best FME for the combination AMZ-CRO was 1.22 with drug concentrations of 1.68 mg/liter for AMZ and 0.17 mg/liter for CRO; the best FME for the combination VAN-CRO was 1.75 with VAN at 0.57 mg/liter and CRO at 0.17 mg/liter. For PRP-2 the best FME obtained for the combination AMZ-CRO was 1.05 with drug concentrations of 11.28 mg/liter for AMZ and 0.64 mg/liter for CRO; the best FME obtained for the combination VAN-CRO was 1.35 with VAN at 0.25 mg/liter and CRO at 1.49 mg/liter. These results demonstrated the synergy of both combinations, AMZ-CRO and VAN-CRO, against PRP strains at drug concentrations achievable in humans. Consequently, either of the combinations can be proposed for use for the treatment of PRP infections.

Amoxicillin↗
PubMed2000

Hepatitis C virus co-infection is a negative prognostic factor for clinical evolution in human immunodeficiency virus-positive patients.

A longitudinal study of human immunodeficiency virus (HIV)-infected individuals followed-up in 13 centres was performed to assess the influence of hepatitis C virus (HCV) on the clinical and immunological evolution of HIV-infected patients. Eight-hundred and twelve HIV-infected patients with known HIV acquisition date, 89 co-infected with HCV, were included in the cohort. Clinical progression was defined as: 30% decrease of Karnofsky's index; and/or 20% body weight loss; and/or acquired immune deficiency syndrome (AIDS)-defining illness; and/or death (except by accident, suicide, or overdose). Immunological progression was defined as a decrease of initial CD4 count to below 200 mm(-3). If immunological progression was not statistically different between groups (P=0.25), clinical progression was significantly faster in HCV-HIV co-infected patients in univariate (P=0.02) and multivariable survival analysis (hazard ratio=1.63, P=0.03). This argues for active management of hepatitis C chronic infection among HCV-HIV co-infected patients.

Adult↗
PubMed2000

HIV-1 protease inhibitors induce an increase of triglyceride level in HIV-infected men without modification of insulin sensitivity: a longitudinal study.

We investigated longitudinally the effect of protease inhibitors (PI) on insulin sensitivity, glycemia, and serum lipids in HIV-infected patients. Ninety-one consecutive patients treated with PI for at least 12 months were included in this study. Fasting glycemia, lipid profile, insulinemia, CD4 T lymphocytes, and plasma HIV-1 RNA were performed at baseline and on PI therapy. Insulin sensitivity and insulin secretion were measured by the homeostasis model assessment (HOMA MODEL) using the fasting glucose and insulin concentrations. Triglycerides (+ 0.34 mmol/l, SD = 1.07, p = 0.001) and cholesterol (+ 1.07 mmol/l, SD = 1.21, p= 0.001) significantly increased on PI therapy. Fasting glycemia, insulin sensitivity, and insulin secretion were not modified after PI therapy. PI therapy significantly increased body mass index (0.35 kg/m2, p < 0.05). Serum lipid changes correlated with changes in the CD4+ cell count. Lipodystrophy was observed in 40.6% of patients treated with PI. Our longitudinal study found that PI therapy had no major impact on fasting glycemia, insulin sensitivity, and insulin secretion. These findings are not consistent with previous cross-sectional studies, which did not include baseline measurements before PI initiation. However, we observed a similar profile of lipid changes induced by PI therapy. These results suggest that PI could be responsible for the development of hypertriglyceridemia by a mechanism independent of insulin resistance which remains to be elucidated.

Adult↗
PubMed1999

[Discontinuing protease inhibitor treatment of HIV-1 patients for intolerance. Longitudinal study of 309 patients].

OBJECTIVES: Determine the frequency and nature of interruptions in HIV-1 protease inhibitor treatment in HIV-infected patients. PATIENTS AND METHODS: A longitudinal study included patients treated with antiretroviral protocols including at least one antiprotease and followed from 1 March 1996 through 1 March 1998. RESULTS: Among the 309 patients followed for the duration of the study, 137 (44.3%) interrupted their antiprotease treatment at least once. Withdrawal was warranted by therapeutic failure in 49.6% of the cases and by drug intolerance in 45.4%. Drug intolerance concerned 37%, 36.7%, 5.7% and 2.9% of the patients taking ritonavir, indinavir, nelfinavir and saquinavir respectively (p < 106). Multivariate analysis demonstrated that saquinavir was significantly associated with better tolerance and with efficacy at least as good as ritonavir or indinavir. The most frequent cause for interrupting treatment were digestive disorders for ritonavir (20% of the treated patients) and lithiasic manifestations for indinavir (9.4%). The ritonavir-hepatitis C association appeared to predispose to drug-induced perturbed liver tests. CONCLUSION: Drug intolerance is a frequent cause of treatment interruption. Therapeutic success in HIV infection requires improved efficacy but also better tolerated antiretorviral drugs, particularly antiretroviral drugs.

Adult↗
PubMed1999

Development of a new experimental model of penicillin-resistant Streptococcus pneumoniae pneumonia and amoxicillin treatment by reproducing human pharmacokinetics.

The increase of penicillin-resistant Streptococcus pneumoniae (PRSP) pneumonia results in a greater risk of antibiotic treatment failure. In vitro data are not sufficient predictors of clinical efficacy, and animal models may be insufficiently contributive, since they often use immunocompromised animals and do not always respect the human pharmacokinetics of antibiotics. We developed an experimental PRSP pneumonia model in immunocompetent rabbits, by using intrabronchial instillation of PRSP (MIC = 4 mg/liter), without any adjuvant. This reproducible model was used to assess amoxicillin efficacy by reproducing human serum pharmacokinetics following 1-g oral or intravenous administrations of amoxicillin every 8 h. Evaluation was performed by using clinical, CT scan, macroscopic, histopathologic, and microbiological criteria. Experimental pneumonia in untreated rabbits was similar to untreated severe human bacteremic untreated pneumonia; in both rabbits and humans, (i) cumulative survival was close to 50%, (ii) red or gray lung congestion and pleuritis were observed, and (iii) lung and spleen concentrations reached 5 and 4 log(10) CFU/g. A 48-h treatment resulted in a significant bacterial clearance in the lungs (1.53 versus 5.07 log(10) CFU/ml, P < 0.001) and spleen (1.00 versus 4.40 log(10) CFU/ml, P < 10(-6)) and a significant decrease in mortality (0% versus 50%, P = 0.02) in treated versus untreated rabbits. No difference was observed on macroscopic and histopathologic lesions between treated and untreated rabbits (P = 0.36 and 0.78, respectively). Similar results were obtained by using a fully penicillin-susceptible S. pneumoniae strain (MIC = 0.01 mg/liter). Our findings suggest that (i) this new model can be contributive in the evaluation of antibacterial agents and (ii) 1 g of amoxicillin three times a day may be sufficient to treat PRSP pneumonia in immunocompetent humans.

Amoxicillin↗
PubMed1998

[Utilization of rapid diagnostic tests for group A streptococcus and and bacteriologic and clinical correlations with acute angina in general medicine].

OBJECTIVES: A prospective study was conducted between November 1995 and May 1996 by 130 general practitioners in France to assess feasibility of a rapid routine diagnostic test for group A streptococcus infection in a general medicine setting and to search for bacteriological and clinical correlations. METHODS: A routine diagnostic test was performed in all patients presenting acute pharyngitis and cultures were ordered in case of positive tests. Among the 2,800 patients included, there were 563 children under 14 years and 2,226 adults. The routine diagnostic test was positive in 393 cases (14%). A culture was obtained in 375 case and isolated group A streptococcus in 324 (11.5% of the total population). The positive predictive value of the routine diagnostic test was 86.4% in this general medicine setting. RESULTS: Comparing clinical signs with the results of the routine diagnostic test showed that an erythematous pultaceous aspect of the pharynx, severe dysphagia and the presence of enlarged nodes were more frequent in patients with streptococcal pharyngitis. The association of these 3 clinical signs with fever > 38 degrees C was also more frequent in patients with a positive routine diagnostic test (OR = 3.3; 95% CI = 2.5-4.4). The triad hoarseness + cough + rhinorrhea was more frequent in subjects with a positive routine diagnostic test (22.7% versus 9%; OR = 2.6; 95% CI = 2.1-4.3). CONCLUSION: The general practitioners who participated in this study found the routine diagnostic test for group A streptococcal pharyngitis was easy to use and compatible with everyday practice. This diagnostic tool was seen as a progress in the management of acute pharyngitis, but only 53.7% of the practitioners were willing to use antibiotics only for cases where a highly specific routine diagnostic test performed during the consultation identifies group A streptococcus. Lack of reimbursement by the national health assurance however makes it impossible to use this test routinely in the general medicine setting.

Acute Disease↗
PubMed1998

Does hepatitis C virus co-infection accelerate clinical and immunological evolution of HIV-infected patients?

OBJECTIVE: To study the influence of hepatitis C virus (HCV) co-infection on clinical and immunological evolution of HIV-infected patients. DESIGN: A longitudinal study of HIV-infected individuals with or without HCV infection, identified at the Infectious Diseases Department of Dijon University Hospital and enrolled in a historical cohort, was performed. METHODS: One hundred and nineteen HIV-infected people co-infected with HCV and 119 matched individuals infected with HIV alone were included in the cohort (median participation time 3 years; range, 2 months to 11.5 years). Clinical progression was defined as one or more of the following: a 30% decrease in the Karnofsky index; a 20% loss of body weight; an AIDS-defining illness (for non-AIDS patients); death (except by accident, suicide or overdose). Immunological progression was defined as a 50% decrease in the initial CD4 T-cell count (for patients with an initial count > 100 x 10(6) cells/l). Effects of HCV co-infection were evaluated using Kaplan-Meier survival analysis and significance was tested using univariate (log-rank and Peto's tests) and multivariate methods (Cox's model). RESULTS: In univariate analysis, immunological progression was not statistically different between the HCV-positive group and the HCV-negative group, whereas clinical progression was significantly faster in HCV-positive patients (P < 0.005, log-rank test). In a multivariate Cox model, clinical progression remained significantly associated with infection by HCV [hazard ratio (HR), 1.64; 95% confidence interval (CI), 1.06-2.55; P < 0.05]. Stratified multivariable analysis retained HCV as a significant prognostic factor of clinical progression (HR, 10.9; 95% CI, 1.09-109.3; P < 0.05) and immunological progression (HR, 2.31; 95% CI, 1.16-4.62; P < 0.02) for patients with an initial CD4 count above 600 x 10(6) cells/l. CONCLUSIONS: Clinical progression is more rapid in HIV-HCV co-infected patients than in HIV-seropositive patients are not infected by HCV. The prognostic value of HCV infection for both clinical and immunological progression is significant at early stages of HIV infection. These findings may argue for active management of hepatitis C infection in co-infected individuals, especially for asymptomatic patients whose CD4 count is above 600 x 10(6) cells/l, to predict and prevent accelerated progression of HCV and HIV diseases.

Adult↗