Biomedical subjects

Michel Ducher

Publications and source records attributed to Michel Ducher.

8 recordsLinked to original sources

PubMed2006

Risk profile in hypertension genesis: A five-year follow-up study.

BACKGROUND: Pathogenesis of primary hypertension remains unclear, because many heterogeneous factors (diet, physiologic, and psychological factors) are simultaneously involved. We have conducted an original analysis to study the influence of the combination of these factors on BP evolution. METHODS: Seven homogeneous clusters were constituted from 213 healthy normotensive subjects taking into account 10 variables. Those variables used to cluster homogeneous "risk profiles" are usually considered as potential risk factors for hypertension: age, body mass index, alcohol consumption, sodium/potassium urinary ratio, systolic blood pressure (SBP) and heart rate response to mental stress, baroreflex sensitivity (BRS), job demand, job latitude, and behavioral pattern (personality score). Five-year BP evolution (DeltaSBP or Deltadiastolic BP [DBP]) was compared between risk profiles. RESULTS: Four clusters of subjects representing about 50% of the population had a significantly higher 5-year DeltaSBP (>or=5 mm Hg) compared to the 5-year DeltaSBP of the two clusters in which SBP did not increase. These four clusters had a low BRS. Two profiles that group six unfavorable risk factors had the most detrimental 5-year DeltaSBP. Interestingly, perceived high job demand in a cluster of younger subjects with a high personality score and a low BRS had also a detrimental SBP evolution. CONCLUSIONS: The major interest of this study is to highlight that hypertension development is not univocal between subjects and that different combinations of factors could explain differential BP evolution in groups of subjects sharing the same risk profile. A lower BRS was a consistent predictor for detrimental 5-year BP evolution.

Adolescent↗

PubMed2006

Is high job strain associated with hypertension genesis?

BACKGROUND: The aim of this analysis was to test, in a large sample of normotensive subjects, the short-term influence of job strain on the onset of hypertension. METHODS: According to the questionnaire of Karasek et al, job strain was divided into four modalities: (high strain, low strain, passive, and active) based on job demand (eg, the need to work hard and quickly) and job latitude (eg, control over skill use, time allocation, and organizational decisions) scores. High strain (HS) was defined by a high demand and a low job decision latitude. Individual data obtained in 926 (age 41 +/- 6 years) healthy normotensive or newly diagnosed hypertensive subjects were analyzed. Subjects participated in two prospective work site surveys designed to assess the influence of job strain on hypertension development. Relationships between job strain modalities and work site blood pressure (BP) levels were assessed using a general linear model. A complementary analysis using the the Pearson Phi coefficient (Z analysis) was implemented to explore nonlinear or scattered relationships between job strain and onset of hypertension. RESULTS: Systolic BP (SBP) was linearly related significantly to BMI and alcohol consumption, whereas diastolic BP (DBP) was related to age. The linear model did not find any relationship between SBP or DBP and job strain modalities. Using the Z analysis, development of systolic hypertension (SBP >140 mm Hg) was significantly associated with high job strain (P < .001). CONCLUSIONS: Our results suggest that there is no global relationship between job strain and BP levels. However our methodology revealed a significant association between job strain and work site BP in a predominantly male subgroup of newly diagnosed hypertensive subjects exposed to high job strain.

Adult↗

PubMed2003

Neither perceived job stress nor individual cardiovascular reactivity predict high blood pressure.

We have reported that high job strain was associated with a significantly higher diastolic blood pressure (DBP) of 4.5 mm Hg during the working hours, irrespective of BP reactivity to a stress test. We report the final results of the first 5-year follow-up study, which aimed to assess the respective influences of perception of professional strain and cardiovascular reactivity to a mental stress test on BP. A cohort of 292 healthy subjects (mean+/-SEM age, 38+/-1 years) was followed up for progression to hypertension outcome, which was defined as an increase in systolic blood pressure (SBP) or DBP >7 mm Hg or a DBP >95 mm Hg during follow-up. None of the subjects was lost to follow-up, and 209 subjects completed the study. The high-strain (HS) group, representing 20.9% of the subjects, was compared with the remaining subjects (non-high-strain [NHS]). Similarly, the subjects with the highest BP stress reactivity (HR; 20.9% of subjects) were compared with the remaining subjects (NHR). Progression to hypertension was reached by 93 subjects (31.8%). Kaplan-Meier survival estimates revealed that neither HS nor HR increased the incidence of progression to hypertension. End-of-follow-up 24-hour ambulatory BPs that were similar in HS and NHS (120+/-2 vs 120+/-1 mm Hg, respectively) and in HR and NHR (122+/-2 vs 120+/-1 mm Hg, respectively) confirmed our findings. Age, alcohol, salt diet, body mass index, and occupation did not interfere with our results. In conclusion, cardiovascular HR and HS do not appear to be major risk markers for future high BP in healthy, young adults.

Adolescent↗

PubMed2003

Sodium intake and blood pressure in healthy individuals.

OBJECTIVE: To investigate further the relationships between blood pressure and sodium intake, which have been claimed to exist, but have not been clearly established, in epidemiological studies. DESIGN AND PARTICIPANTS: A 2-year follow up study of a cohort of 296 healthy volunteers working in the same company. RESULTS: Consistent with previously reported findings, covariance analysis in the entire population, including multivariate analysis to examine the potential influence of confounding variables, failed to identify a significant relationship between blood pressure and sodium intake or between their respective changes within 2 years. To test the hypothesis of a heterogeneous distribution of salt sensitivity, we calculated the statistical dependence between blood pressure and sodium intake using the coefficient analysis that quantifies the prevalence of a statistical link between two variables. A significant dependence (P < 0.05) between diastolic (DBP) or systolic (SBP) blood pressure and sodium intake was found in 16 and 5% of the participants, respectively. The analysis of the 2-year changes in blood pressure and sodium intake reinforced our findings. Our finding of a relationship between blood pressure and sodium intake in only a few individuals may explain the lack of a global relationship between these two variables investigated by the covariance analysis in our study.(Rho) CONCLUSION: Our results suggest that 5-16% of healthy individuals have a 'salt-dependent blood pressure' and might benefit from a reduction in dietary salt intake.

Adult↗

PubMed2003

Aminoglycoside nephrotoxicity: modeling, simulation, and control.

The main constraints on the administration of aminoglycosides are the risks of nephrotoxicity and ototoxicity, which can lead to acute, renal, vestibular, and auditory toxicities. In the present study we focused on nephrotoxicity. No reliable predictor of nephrotoxicity has been found to date. We have developed a deterministic model which describes the pharmacokinetic behavior of aminoglycosides (with a two-compartment model), the kinetics of aminoglycoside accumulation in the renal cortex, the effects of aminoglycosides on renal cells, the resulting effects on renal function by tubuloglomerular feedback, and the resulting effects on serum creatinine concentrations. The pharmacokinetic parameter values were estimated by use of the NPEM program. The estimated pharmacodynamic parameter values were obtained after minimization of the least-squares objective function between the measured and the calculated serum creatinine concentrations. A simulation program assessed the influences of the dosage regimens on the occurrence of nephrotoxicity. We have also demonstrated the relevancy of modeling of the circadian rhythm of the renal function. We have shown the ability of the model to fit with 49 observed serum creatinine concentrations for a group of eight patients treated for endocarditis by comparison with 49 calculated serum creatinine concentrations (r(2) = 0.988; P < 0.001). We have found that for the same daily dose, the nephrotoxicity observed with a thrice-daily administration schedule appears more rapidly, induces a greater decrease in renal function, and is more prolonged than those that occur with less frequent administration schedules (for example, once-daily administration). Moreover, for once-daily administration, we have demonstrated that the time of day of administration can influence the incidence of aminoglycoside nephrotoxicity. The lowest level of nephrotoxicity was observed when aminoglycosides were administered at 1:30 p.m. Clinical application of this model might make it possible to adjust aminoglycoside dosage regimens by taking into account both the efficacies and toxicities of the drugs.

Adult↗

PubMed2003

Aminoglycoside dosages and nephrotoxicity: quantitative relationships.

OBJECTIVE: To develop a model that relates the probability of occurrence of nephrotoxicity to the cumulative area under the curve (AUC) of amikacin serum concentration. DESIGN AND PATIENTS: This was a retrospective study of two groups of patients in whom nephrotoxicity was observed after administration of amikacin. The first group consisted of patients treated with once-daily administration (ODA) [n = 13]. The second group consisted of patients treated with twice-daily administration (TDA) [n = 22]. MAIN OUTCOME MEASURES: The probability of nephrotoxicity occurrence. RESULTS: The model is a powerful tool to represent and describe the influence of the dosage regimen on aminoglycoside nephrotoxicity. The onset of nephrotoxicity is delayed in the ODA group (p = 0.01) for the same total daily dose among the two groups. The cumulative serum AUC values at onset of nephrotoxicity were greater for the ODA group (p = 0.029). In addition, for the same probability of nephrotoxicity occurrence (50%), the cumulative AUC for the ODA dosage regimen is 2 613 mg. h/L versus only 1 521 mg. h/L for the TDA dosage regimen. The difference in nephrotoxicity between ODA and TDA is greatest for a cumulative AUC of 2 495 mg. h/L, which corresponds to standard therapy with amikacin 900 mg/day during a 7-day period, i.e. 15 mg/kg/day for a 60kg patient with normal renal function (initial creatinine clearance >80 mL/min). For an AUC above 2 495 mg. h/L, the difference in nephrotoxicity decreases slowly to zero. This result means that ODA is especially justified when the treatment is administered over a short duration, i.e. less than 7 days. CONCLUSIONS: The utility of selecting ODA in order to obtain less nephrotoxicity in comparison with TDA is therefore not established when the treatment is prolonged. In clinical use, the choice of the dosage regimen is not clear-cut, and both expected efficacy and expected toxicity must be taken into account in order to obtain an overall optimisation of each patient's therapy.

Amikacin↗

PubMed2002

Stress-induced renal alterations in normotensives offspring of hypertensives and in hypertensives.

BACKGROUND: Scarce information is available on stress-induced renal behavior in humans, especially in normotensives offspring of hypertensives (HP) and in hypertensives (HT). METHODS: Ten HP and 10 HT were compared to 10 normotensives with normotensive parents (NP). Systolic blood pressure (SBP) and renal functional parameters were determined during rest and stress periods. RESULTS: The stress SBP reactivity was significantly (P < .05) higher in HP than in NP and HT. At rest, HP were characterized by a significantly (P < .05) higher glomerular filtration rate. Stress significantly reduced glomerular filtration rate (-14 +/- 4 mL/min/1.73 m2, P < .05) only in HT. Renal plasma flow significantly (P < .05) decreased during stress in NP (-35 +/- 16 mL/min/1.73 m2) and in HT (-49 +/- 25 mL/min/1.73 m2), whereas it did not change in HP. The resulting filtration fraction increased significantly during stress only in NP (1.5% +/- 0.6%, P < .05). Despite the increase in BP, stress induced a similar decrease in sodium excretion rate in NP (-52 +/- 26 micromol/min) and in HT (-56 +/- 24 micromol/min). The stress-induced sodium reabsorption occurred only in the proximal part of the tubules (lithium clearance). In HP, stress did not alter either sodium excretion rate or plasma renin activity. CONCLUSIONS: The stress-induced renal modifications are characterized by an efferent vasoconstriction and a paradoxical increase in sodium reabsorption that occurred in the proximal part of the tubules in NP. In HP, genetically at risk of hypertension, basal renal alterations may explain a different stress-induced renal behavior. In HT, stress-induced increase in sodium reabsorption may be involved in the sustained BP level.

Aldosterone↗

PubMedDate not supplied

How to limit screening of patients for atheromatous renal artery stenosis in two-drug resistant hypertension?

BACKGROUND: The DRASTIC model based on nine variables (age, gender, recent onset of hypertension, smoking status, body mass index (BMI), abdominal bruit, atherosclerosis, dyslipidemia and creatininemia) has been proposed to predict renal artery stenosis (RAS) occurrence. METHODS: In a prospective multicenter study, the clinical usefulness of the DRASTIC model was checked in 336 patients with two-drug resistant hypertension. RAS was excluded using at least color Doppler sonography. RAS was diagnosed using at least renal angiography. The statistical dependence (Z(Rho)) analysis was applied to investigate further the relationships between each variable and presence of RAS. RESULTS: The prevalence of RAS (n=51) was 15%. The goodness-of-fit test that compared observed RAS to predicted RAS using the DRASTIC model was not significant. Accordingly, the multivariate logistic regression indicated that only three parameters (abdominal bruit, atherosclerotic vascular disease and BMI <25 kg/m2) were significantly linked to RAS. The Z(Rho) methodology revealed that calculated renal function <60 ml/min and age >58 yrs (median) were also significantly linked to RAS. No variable or combination of variables offered satisfactory positive predictive values for the RAS diagnosis. The combination of the five significantly linked variables had a negative predictive value of 98%, and allowed RAS detection with a sensitivity of 96%. In our population, RAS screening could have been avoided in 30% of our patients screened. CONCLUSIONS: The DRASTIC model was unsuitable for clinical use in our sample population. In our population, renal arteries were considered stenosis free with a probability of 98% in refractory hypertensive overweight patients, aged < or = 58 yrs, with satisfactory renal function and without both abdominal bruit and atherosclerotic vascular disease.

Abdominal Pain↗