Search PubMed⌕ Search

Biomedical subjects

J Menard

Publications and source records attributed to J Menard.

At least 37 records · Page 2Linked to original sources
PubMed1999

In vivo assessment of captopril selectivity of angiotensin I-converting enzyme inhibition: differential inhibition of acetyl-ser-asp-lys-pro and angiotensin I hydrolysis.

Angiotensin I-converting enzyme (ACE) is a zinc metallopeptidase that plays a major role in blood pressure regulation. The demonstration that the hemoregulatory peptide acetyl-Ser-Asp-Lys-Pro (AcSDKP) is a natural and specific substrate of the N-active site of ACE suggests that this enzyme may have a new physiological role such as the modulation of hematopoietic stem cells. In vitro studies have shown that ACE inhibitors displayed various potencies in inhibiting the degradation of different natural or synthetic substrates of ACE, among which captopril inhibits AcSDKP hydrolysis more potently than angiotensin I hydrolysis. To look for this selectivity in vivo, we investigated the pharmacodynamic effect of increasing doses of captopril (0.01-10 mg/kg) during the 90 min after i.v. administration to spontaneously hypertensive rats. Plasma and urinary AcSDKP levels were measured. The renin-angiotensin system was evaluated by measurements of ACE activity in plasma samples, using the synthetic substrate Hip-His-Leu, by determinations of plasma renin concentrations and measurements of arterial blood pressure. The results showed that captopril (0.01-0.3 mg/kg) selectively inhibited AcSDKP hydrolysis, with limited effects on the renin-angiotensin system. AcSDKP levels in plasma and urine rose to a plateau 4 times the basal level for doses more than 0.3 mg/kg. All of the parameters reflecting the renin-angiotensin system were significantly affected at doses of 1 and 10 mg/kg. The present study therefore confirms that captopril can be used to protect hematopoietic stem cells during antitumor chemotherapy while having only a limited effect on cardiovascular homeostasis.

Angiotensin I↗
PubMed1999

[Combined blockade of the renin-angiotensin system].

In view of the internal counter-regulation mechanisms of the renin-angiotensin system (RAS), complete blockade would not seem to be possible if only one of its components is targeted. Instead of increasing the dosage of an angiotensin converting enzyme (ACE) inhibitor or that of an angiotensin II antagonist (AA), blockade of the system at two different levels by neutralising the internal counter-regulation mechanism could provide more effective blockade and, therefore, more pronounced biological effects. For this reason, the authors undertook two studies in a model of mild salt depletion of a normotensive subject, which showed additive effects on the lowering of the blood pressure and renin secretion during combined administration of captopril and losartan, then enalapril and losartan. There was no additive effect on plasma aldosterone levels. The administration of the ACE inhibitor neutralised the expected increases in plasma Angiotensin II values due to the losartan. All combinations of ACE inhibitor and AA were tested in spontaneous hypertensive rats using a dosage scale from 1 to 30, the results of which showed the beneficial effects of combined blockade on left ventricular mass and the deleterious effects on renal function when blockade of the RAS is too complete. Based on the results obtained in normotensive subjects and homogeneous groups of hypertensive animals, the authors conclude that low doses of an AA and of an ACE inhibitor is more effective in lowering the blood pressure than higher doses of each drug administered separately. How can these results be applied clinically in hypertension and cardiac failure? The choice between increasing the dose of each of the two drugs or the association of low doses of both drugs will depend more on the tolerance of each therapeutic strategy than on the efficacy. The choice between the two strategies will also depend on the demonstration of consequences specific to each modality of inhibition of the system, especially with respect to the effects of accumulation of bradykinin and to stimulation of type 2 receptors. The additive effects of a combined treatment should be validated by repeated administration in hypertensive patients.

Angiotensin II↗
PubMed1999

Effect of angiotensin-converting enzyme inhibition on plasma, urine, and tissue concentrations of hemoregulatory peptide acetyl-Ser-Asp-Lys-Pro in rats.

The hemoregulatory peptide Acetyl-Ser-Asp-Lys-Pro (AcSDKP) has been reported to accumulate in plasma and urine after the oral administration of angiotensin-converting enzyme (ACE) inhibitors in humans. It is unknown whether such an accumulation also occurs in tissues. We administered captopril (3, 10, or 30 mg/kg) orally for 2 weeks to Wistar rats. In a second experiment, captopril (10 mg/kg) was administered for 9 days and was followed by a 1-h i.v. infusion of either AcSDKP (0.1 or 2 mg/kg) or saline on day 9. Captopril alone dose-dependently increased plasma AcSDKP by a factor of 3 to 5 and urine AcSDKP by a factor of 3. It slightly increased renal and pulmonary AcSDKP concentrations but did not affect AcSDKP concentrations in bone marrow and spleen. The combination of AcSDKP (2 mg/kg) and captopril gave very high AcSDKP concentrations in plasma and urine and increases in AcSDKP concentration by factors of 27 in kidney, 5.5 in lung, and 6.9 in the extracellular fraction of bone marrow. In contrast, no change was observed in the AcSDKP concentration in spleen and in the intracellular fraction of bone marrow. In conclusion, during chronic ACE inhibition in rats, AcSDKP levels slightly increased in organs with high ACE contents. No such increase occurred in hematopoietic organs. AcSDKP had to be combined with captopril to significantly increase its concentration in tissues other than the spleen. The possibility of pharmacologically increasing AcSDKP levels in the extracellular fraction of bone marrow may be of value for protecting hematopoietic cells from the toxicity of cancer chemotherapy.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Vascular and cardiac remodeling in world class professional cyclists.

BACKGROUND: Numerous studies have demonstrated that left ventricular (LV) hypertrophy is often associated with conditioning. METHODS AND RESULTS: The aim of the study was to evaluate cardiac and carotid artery changes induced by professional cycling. We collected M-mode left ventricle and B-mode right common carotid artery data from 149 male professional cyclists before the 1995 "Tour de France" race and 52 male control subjects. LV mass indexed to body surface area in cyclists was double that in control subjects, with no overlap of 95% confidence intervals (cyclists 100.9 to 187 g/m2 and control subjects 51.8 to 96.3 g/m2). Both mean arterial diameter and mean arterial diastolic intima-media thickness (IMT) were 13% higher in cyclists than in control subjects, with overlap of 95% confidence intervals (for arterial IMT 0.45 to 0.65 mm in cyclists and 0.38 to 0.60 mm in control subjects). CONCLUSIONS: Our results suggest that intense cycling has an effect on the cardiovascular system, more pronounced on the left ventricle and less pronounced on large arteries. Nevertheless, athletic training should be considered as a potential determinant of carotid modification.

Adult↗
PubMed1998

Short-term effects of withdrawing angiotensin converting enzyme inhibitor therapy on home self-measured blood pressure in hypertensive patients.

The aim of this study was to compare blood pressure rise after interruption of two angiotensin converting enzyme (ACE) inhibitors in hypertensive patients. After a 2-week placebo run-in period, hypertensive patients were treated with either trandolapril 2 mg once daily or perindopril 4 mg once daily for 4 weeks in a double-blind design. A placebo was then administered for 1 week. Three periods of 1-week home self-measured blood pressure (SMBP) were programmed: end of placebo run-in period, end of treatment period, and final withdrawal placebo period. Every day, three consecutive measurements were requested both in the evening and in the morning. Individual reversion to baseline BP level was studied in the subgroup of patients responding to therapy (evening diastolic SMBP decrease > or =6 mm Hg). The ratio (R) of mean post-drug DBP lowering (residual effect) over evening on-drug DBP lowering (full effect) was used to study reversion to baseline. Patients exhibiting a lower value than the median of this ratio were called Reverters, whereas others were called Nonreverters. One hundred-nineteen patients entered the analysis. During the treatment period, mean SMBP decreased significantly, from 150 +/- 14/97 +/- 7 mm Hg to 139 +/- 15/91 +/- 9 mm Hg (all P < .001). The on-drug BP level was similar in the evening in the two treatment groups. However, both systolic and diastolic morning SMBP levels were significantly lower in the trandolapril group. After drug discontinuation, the mean BP level significantly rose to 144 +/- 14/94 +/- 9 mm Hg (all P = .01) but remained lower than the baseline BP values (P = .003 for SBP and P = .002 for DBP). The post-drug BP level was significantly lower in the trandolapril group than in the perindopril group. Seventy-four patients were responders to therapy. In this subgroup, the median of the R ratio used to analyze reversion to baseline after drug discontinuation was 44%. Nonreverters were characterized by a sustained on-drug BP decrease, compared to Reverters. We therefore conclude that ACE inhibitor treatment withdrawal is accompanied by a rapid rise in BP (within 48 h), followed by a 5-day BP plateau that is lower than the initial level. Reverters to baseline after drug discontinuation were more likely to be insufficiently controlled during therapy, particularly in the morning. The longer duration of action of trandolapril was associated with a lower BP level during both the morning during the active treatment phase and the 1-week posttreatment phase.

Adult↗
PubMed1998

Does the bed nucleus of the stria terminalis mediate fear behaviors?

The bed nucleus of the stria terminalis (BNST) has been implicated in autonomic and hormonal reactions to fearful stimuli, but its role in behavioral reactions to these stressors is less clear. This is puzzling, because 2 closely related areas, the septum and the amygdala, have been repeatedly implicated in fear behaviors. To investigate further, the behavioral effects of BNST lesions were compared to those of septal and amygdaloid lesions in 2 models of rat anxiety: the plus-maze and shock-probe tests. Septal lesions inhibited rats' open-arm avoidance in the plus-maze and suppressed burying of the shock-probe, whereas amygdaloid lesions specifically inhibited shock-probe avoidance. However, BNST lesions produced none of these anti-fear effects; thus, its involvement in the behavioral expression of fear is questionable.

Amygdala↗
PubMed1998

Is barakol anxiolytic?

A recent report suggested that barakol, a biologically active extract of the south-east Asian plant, Cassia siamea, has anxiolytic properties. The purpose of the present study was to replicate and extend these findings by examining the dose-response effects of barakol (0-20 mg/kg) in two pharmacologically validated tests of rat anxiety: the elevated plus-maze and the shock-probe burying tests. Although the purity of our sample of barakol was confirmed by chemical analysis, we found no evidence of its anxiolytic effects in either the plus-maze or shock-probe burying tests.

Analysis of Variance↗
PubMed1998

The septum and the hippocampus differentially mediate anxiolytic effects of R(+)-8-OH-DPAT.

Infusing the 5-HT1A receptor agonist R(+)-8-OH-DPAT into the septum or hippocampus reduced the fear responses of rats differentially in the elevated plus-maze and shock-probe burying tests, two rat models of anxiety. Intra-septal infusions of R(+)-8-OH-DPAT (5 and 10 microg) produced dramatic reductions in rat burying behavior in the shock-probe test, whereas it did not alter rat open-arm activity in the plus-maze test, across a wide range of doses (0.1, 0.25, 5 and 10 microg). Conversely, intra-hippocampal infusions of R(+)-8-OH-DPAT (0.1 and 5 microg/side) produced substantial increases in open-arm activity in the plus-maze test, but did not alter rat burying behavior in the shock-probe test. These dissociations suggest that 5-HT1A receptors in the septum and hippocampus exert parallel but distinct control over different fear reactions.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1997

Dissociations among the anxiolytic effects of septal, hippocampal, and amygdaloid lesions.

Fear reactions of rats given bilateral lesions to the septum, hippocampus, or amygdala were compared with those of rats given sham lesions, in 2 animal models of anxiety: the shock-probe burying test and the elevated plus-maze test. Septal lesions produced anxiolytic effects in both tests (i.e., an increase in open-arm activity and a decrease in burying), whereas hippocampal and amygdaloid lesions produced neither of these effects. On the other hand, hippocampal and amygdaloid lesions impaired rats' passive avoidance of the electrified shock-probe, whereas septal lesions did not. These dissociations suggest that limbic structures such as the septum, amygdala, and hippocampus exert parallel but distinct control over different fear reactions.

Amygdala↗
PubMed1996

Influence of obesity on the diagnostic value of electrocardiographic criteria for detecting left ventricular hypertrophy.

Easily applicable, clinically relevant electrocardiographic criteria are needed to screen large populations for left ventricular (LV) hypertrophy. The aim of this study was to evaluate, in a population of 380 hypertensive patients of both sexes, whether obesity modified the diagnostic performance of Sokolow-Lyon and Cornell voltage criteria by comparing them with echocardiographic evaluations using different indexation methods for LV mass presentation (body surface area and various powers of the height variable). For the population as a whole, Cornell voltage was better correlated to LV mass than was Sokolow-Lyon voltage (r = 0.48 and 0.36, respectively). The poorest performance of Sokolow-Lyon voltage was observed among obese patients (best r = 0.1 and 0.21 in obese women and men, respectively). Sensitivities were assessed at a 95% specificity level. In nonobese patients, using sex-adjusted voltage values (43 and 36 mm in men and women, respectively, for Sokolow-Lyon voltage, and 28 and 25 mm for Cornell voltage), the sensitivities of Cornell voltage and Sokolow-Lyon voltage were similar in men and women (near 22% and 36%, respectively), whatever the indexation method used for LV mass. In obese patients, Cornell voltage sensitivity was similar to that of nonobese patients, whereas Sokolow-Lyon voltage had a much poorer sensitivity (<10%). For simple LV hypertrophy detection criteria, Sokolow-Lyon voltage should be avoided in obese hypertensive patients and replaced by the Cornell voltage criteria, which are not influenced by the presence of obesity.

Body Mass Index↗
PubMed1996

The number needed to treat: a clinically useful nomogram in its proper context.

The number needed to treat is a meaningful way of expressing the benefit of an active treatment over a control. It can be used either for summarising the results of a therapeutic trial or for medical decision making about an individual patient, but its use at the bedside has been impeded by the need for time consuming calculations. A nomogram has therefore been devised that will greatly simplify the calculations. Since calculations are now easy, the number needed to treat can be used to access the value of several interventions, although it does have its limitations. In particular it should not be used when it is not known whether the relative risk reduction associated with an intervention is constant for all levels of risk, or for periods of time longer than that studied in the original trials.

Clinical Trials as Topic↗
PubMed1996

Does tolerance develop to the anxiolytic effects of septal lesions?

Previous studies have shown that septal lesions produce anxiolytic-like effects in tests of rat "anxiety" (i.e., septal lesions increase open-arm exploration in the elevated plus-maze test and decrease burying in the shock-probe burying test). The present experiment examined whether "tolerance" develops to the anxiolytic effects of septal lesions, in a manner similar to that of anxiolytic drugs. Accordingly, septal- and sham-lesioned rats were repeatedly tested in the elevated plus-maze. As in previous studies using anxiolytic drugs, septal lesions produced a clear anxiolytic effect on the first test day, but this effect virtually disappeared by the third test day. Although these findings suggest "tolerance" had developed to the anxiolytic effects of septal lesions, these same rats showed clear evidence of anxiolysis when they were subsequently tested in the shock-probe burying paradigm. A second experiment showed that these basic effects did not depend critically on time since surgery. Thus, the diminution of anxiolysis induced by septal lesions in the elevated plus-maze is test-specific and does not reflect a general recovery of normal fear reactions.

Animals↗
PubMed1996

Lateral and medial septal lesions reduce anxiety in the plus-maze and probe-burying tests.

Previous studies have shown that septal lesions produce anxiolytic-like effects in rat models of "anxiety" (i.e., septal lesions, like anxiolytic drugs, increase rats' open-arm exploration in the elevated plus-maze test and decrease rats' burying behavior in the shock-probe burying test). Although these anxiolytic effects occur after lesions to posterior (but not anterior) regions of the septum, their anatomical specificity has not been clearly defined with respect to classical subdivisions of the septum, such as the medial and lateral nuclei. Thus, in Experiment 1, we compared the effects of lateral or medial septal lesions on rats' anxiety reactions in the elevated plus-maze and shock-probe burying tests. Contrary to the "anxiogenic" effects of septal lesions recently found in a "conflict" model of anxiety, we found that both lateral and medial septal lesions produced equivalent anxiolytic effects in the plus-maze and shock-probe tests. In Experiment 2, we found similar anxiolytic effects whenever lesions included septal areas just anterior to the fornix (i.e., the lateral septum) but not when septal lesions were restricted to areas just posterior to the fornix (i.e., the septofimbrial and triangular septal nuclei). Taken together with our previous results, these data suggest that classical subdivisions of the septum bounded rostrally by the genu of the corpus callosum and caudally by the fornix play an exclusively excitatory role in the control of anxiety, as expressed in the plus-maze and shock-probe burying models.

Animals↗
PubMed1996

Selective recognition of M235T angiotensinogen variants and their determination in human plasma by monoclonal antibody-based immunoanalysis.

The common M235T mutation of human angiotensinogen has been shown to be associated with a 10-20% increase in plasma angiotensinOgen level and increased frequency of essential and pregnancy-induced hypertension. The detection of such a common factor in the plasma of individuals at risk could be a useful tool for modern molecular-based medicine. The recognition of M235T variants was investigated using four monoclonal antibodies (mAbs) directed against human angiotensinogen; two immunometric assays were developed. The first assay (using mAbS 7B2 and 4G3) allowed the direct determination of angiotensinogen concentrations and did not show a significant difference with the enzymatic measurement of angiotensinogen. The second assay (using mAbs 1H8 and 1C11) showed a fine distinction between the T235 mutant and M235 wild-type forms of angiotensinogen, with a greater affinity for the latter, as confirmed by biosensor BIAcore experiments. This assay was extremely sensitive in measuring the proportions of the M235 and T235 forms present in the test samples, the first time such a distinction has been achieved in the serpin family. The simple immunoanalysis of the plasma allowed the direct determination of the M235T genotype of the individual tested. Furthermore, it was shown that the T174M mutation, described as being in complete linkage disequilibrium with the M235T mutation, had no influence on these results. Moreover, this assay suggested the presence of the M235 and T235 angiotensinogens in approximately equal amounts in heterozygous plasmas. In conclusion, the immunometric assay described in this study should provide original tools for investigating the relationship between M235T genotype, plasma angiotensinogen levels, and regulation of blood pressure.

Angiotensinogen↗
PubMed1996

[Prevalence, treatment and control of hypertension in family practice patients in France during 1994].

The aim of this study was to measure the percentage of patients with hypertension, treated hypertension and controlled hypertension, using data collected over one week by 235 general practitioners well representative of the French medical population and selected by SOFRES Médical. Practitioners had to carry out their own survey over a period of one week on all patients above 18 years of age who visited their office. They were initially instructed to use the same type of mercury sphygmomanometer, equiped with the same pneumatic cuffs of different sizes. Three consecutive blood pressure measurements were effected, the last two were recorded. Patients were considered as hypertensive if the mean of the two recorded BP measurements was > or = 140-90 mmHg, or < 140-90 mmHg under pharmacological treatment. Hypertensive patients were considered as controlled when their blood pressure levels were overall < 140-90 mmHg under treatment. According to age, two other control levels were analysed: blood pressure < 160-95 mmHg before 65 years and blood pressure < 160-90 mmHg at 65 years or more. Among 12,351 patients, 5,020 are hypertensive (4%), 2,985 under pharmacological treatment (59%) and 2,035 without treatment (4%). Among untreated patients, 9% had an hypertension above the borderline values. Before 65 years, 28% had an under treatment blood pressure < 140-90 mmHg and 71% < 160-95 mmHg. Among 65 years or more hypertensive patients, 21% had an under treatment blood pressure < 140-90 mmHg and 60% < 160-90 mmHg. Before 65 years, 25% among patients with a monotherapy remained with a blood pressure > 160-95 mmHg and 34% with a blood pressure > 160-90 mmHg among those of 65 years or more; 230 patients (5%) remained in high risk with a blood pressure > 180-105 mmHg. 176 untreated and 54 despite their treatment. This study carried out in French medical practice yield two main conclusions regarding the management of hypertension: as the prevalence of hypertensive patients is 41%: one patient out of two, high blood pressure has to be a main aim for the medical teaching. Even if a reasonable control of the blood pressure is achieved in most cases, blood pressure got a normal level for 24% only of treated hypertensive patients and too many patients were keeping high risk because they have been not or not enough treated. This study, as a real audit, gives some useful informations to general practitioners in order to improve their scores.

Adolescent↗
PubMed1996

Interactive electronic teaching (ISIS): has the future started?

Medical education of hypertensives as well as of other asymptomatic cardiovascular risk patients requires individualized, interactive and attractive strategies. Electronic teaching set up in hospital or clinic settings opens the way of the future, saving time and allowing more advantageous use of caretakers. ISIS (Initiation Sanitaire Informatisee et Scenarisee), a French computer assisted program for cardiovascular risk patients, combines a scientific information, divided in 12 sequential but independent modules, with a recreative imaginary trip in the world of ancient Egypt. To test the impact of this tool on patient health information retention, 158 hypertensives hospitalized in a day-hospital clinic were randomized into an intervention or ISIS group (IG, n = 79) and a control group (CG, n = 79). Both groups received cardiovascular education through standard means. In addition, IG patients underwent a 30 to 60 min session on the computer. Cardiovascular knowledge was tested by a nurse administering a standardized 28-item questionnaire before and two months after education. Retesting was done by telephone interview. A total of 138 completed questionnaires (69 from each group) were analyzed. Overall mean cardiovascular knowledge score before education (14.3 +/- 4.2, range 4-25) improved significantly after education (3.7 +/- 3.5, p = 0.0001). This improvement was more important in the IG than the CG (3.8 +/- 3.6 vs 2.4 +/- 3.2 respectively, p = 0.02), especially in hypertensives having a known disease for more than six months. Isis is now available in two languages: French and English. Patients' satisfaction and the conclusion of this comparative trial encourage confirmation of these first results in other French or English speaking populations, in order to test the long term effects of structured electronic teaching sessions on health behaviour, and to promote a wide use of computers and multimedia communication in hypertension control programs.

Adult↗
PubMed1995

Which definition for echocardiographic left ventricular hypertrophy?

Left ventricular (LV) hypertrophy is diagnosed on the basis of LV mass measurement at echocardiography. However, various thresholds for defining LV hypertrophy have been published, ranging from 111 to 134 g/m2 and from 100 to 125 g/m2 in men and women, respectively. The aim of our study was to evaluate variations in the prevalence of LV hypertrophy induced by the application of different threshold values among hypertensive subjects. LV mass was calculated in 349 hypertensive patients from an M-mode LV tracing obtained by left parasternal view in 83% and by subcostal view in 17% of patients. The prevalence of LV hypertrophy ranged from 17% to 39%, according to the threshold value applied (from 10% to 47%, and from 19% to 39% in women and men, respectively). As expected, the prevalence of LV hypertrophy in obese patients of both sexes was higher when applying the usual height-indexed threshold (143 and 102 g/m for men and women, respectively) than when applying the usual body surface area-indexed threshold (134 and 110 g/m2 for men and women, respectively). The use of normalized thresholds when comparing different indexation methods (in this case, 145 g/m for men, 120 g/m for women) will minimize these variations in part due to the threshold choice. Considering the clinical and therapeutic implications associated with the presence of LV hypertrophy, better standardization of definitions is needed; this could be based either on better-designed cooperative normality studies or meta-analysis of risk stratification.

Adult↗