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Biomedical subjects

D Guez

Publications and source records attributed to D Guez.

At least 37 records · Page 2Linked to original sources
PubMed1998

[Long-term outcome of infra-inguinal endovascular surgery for critical ischemia].

STUDY AIM: Endovascular surgery can be proposed as an alternative to infrainguinal conventional surgery in critical ischemia. The aim of this study was to report the latest results of our series of 186 patients. MATERIALS AND METHODS: One hundred and eighty-six patients (100 women and 86 men; mean age 74.5 +/- 13 years) were treated for pain during rest (31.5%), gangrene (58%), or ischemic ulcer (10.5%). The lesions were unilateral (n = 172) or bilateral (n = 14). Two hundred eighty-seven target lesions were treated: for stenosis (n = 168) or occlusion (n = 119): of superficial femoral artery (31.7%), popliteal artery (40%) or tibial arteries (28.3%). RESULTS: Technical success was achieved in 81% (15% amputations). The in-hospital mortality rate was 6.5%. The cumulative patency rate was 61 +/- 3% at 12 months, and 52 +/- 6% at 48 months. The limb salvage rate was 87 +/- 3% at 12 months and 82 +/- 4% at 48 months. Thirteen potential factors of patency were analyzed: the only predictive factors affecting patency were occlusion versus stenosis, and the use of atherectomy (Log rank test: P < 0.001 and P < 0.0001). CONCLUSION: Despite a risk of technical failure and of mid-term restenosis, endovascular surgery for critical ischemia provides a fair long-term limb salvage rate.

Aged↗
PubMed1998

Antioxidant properties of indapamide, 5-OH indapamide and hydrochlorothiazide evaluated by oxygen-radical absorbing capacity and electron paramagnetic resonance.

The aim of these experiments was to investigate the radical scavenging properties of three diuretics: indapamide (IND) and its major metabolite, 5-OH indapamide (5-OH IND), compared to a reference diuretic, hydrochlorothiazide (HTZ). Electron Paramagnetic Resonance (EPR) was used to determine the scavenging abilities of these compounds on enzymatically produced superoxide radical anion, with 5,5-dimethyl-1-pyrroline N-oxide (DMPO) used as a spin-trap. These experiments revealed that IND and specially 5-OH IND were effective superoxide radical anion scavengers at 0.2 mg/ml. In the second part of these studies, allophycocyanin was used as an indicator of free radical mediated protein damage. In the assay, 2,2'-azobis(2-amidinopropane) hydrochloride (AAPH) was used as a peroxyl radical generator, Trolox (a water-soluble analogue of vitamin E) as a control standard, and the loss of allophycocyanin fluorescence was monitored. The antioxidant effects of the diuretics were expressed in oxygen-radical absorbing capacity (ORAC), where one ORAC unit equals the net protection produced by 1 microM Trolox. HTZ showed no protection up to 100 microM final concentration, whereas IND and 5-OH IND showed linear correlation with respect to concentration when expressed in ORAC units: 5-OH IND induced the highest protection against peroxyl radical. The above observations suggested that IND and 5-OH IND are potent radical scavengers, with the metabolite 5-OH IND having a superior antioxidant potency than IND. By contrast, HTZ had no effect. These radical scavenging properties of 5-OH IND may be of clinical interest for vascular protection and may help to protect the heart from oxidative injury.

Antioxidants↗
PubMed1998

The very low density lipoprotein (VLDL) receptor is a genetic susceptibility factor for Alzheimer disease in a European Caucasian population.

The epsilon4 allele of the apolipoprotein E gene (APOE) constitutes a major genetic susceptibility factor for Alzheimer disease (AD). Recently, a polymorphic triplet (CGG) in the very low density lipoprotein receptor (VLDL-R) gene, coding for a receptor binding only apoE-containing lipoproteins, was associated with AD in a Japanese population but not in Caucasian American populations. We explored this association and the potential interaction with the APOE polymorphism in a Caucasian sample of sporadic AD and control subjects of similar ages of European origin. The allelic distribution of the VLDL-R polymorphism differed significantly between Japanese and Caucasian populations (p < 0.0001). However, in our population, the presence of at least one VLDL-R 5 repeat allele increased significantly (p < 0.0003) the probability to develop AD after 65 years of age in APOE epsilon4 allele bearers.

Aged↗
PubMed1998

Centralized echocardiogram quality control in a multicenter study of regression of left ventricular hypertrophy in hypertension.

OBJECTIVE: To test the feasibility and utility of instituting centralized echocardiographic quality control during a multicenter study of regression of left ventricular hypertrophy in hypertension. DESIGN AND METHODS: The LIVE (Left Ventricular Hypertrophy: Indapamide Versus Enalapril) study is an ongoing multicenter, double-blind, controlled study of regression of echocardiographic left ventricular mass index in hypertensive patients with left ventricular hypertrophy (left ventricular mass indexes > 100 g/m2 for women and > 120 g/m2 for men) treated for 1 year with 1.5 mg indapamide sustained-release coated tablets versus 20 mg enalapril. A centralized evaluation committee has validated a prestudy sample echocardiogram from each center, and is now reviewing all videotapes recorded during this study for quality control; final results will be based on a further randomized blinded analysis by this centralized evaluation committee. RESULTS: Since December 1994, 878 patients have been preselected (videoechocardiographic recordings sent for assessment), 645 selected (videoechocardiographic recordings validated), and 576 randomly allocated to treatment. After preliminary quality control, 27% (233) of baseline echocardiograms were rejected by our centralized evaluation committee, and 22% (142) of postinclusion echocardiographic measurements had to be repeated, mainly because they were of poor echogenic quality. Analysis of approved baseline echocardiograms for the first 274 randomly allocated patients with digitized data showed that there was a significant correlation between centralized evaluation committee and investigator calculations of left ventricular mass index (r = 0.76, P < 0.001), with consistently higher values for investigator calculations, independently of level of left ventricular mass index (correlation between difference and mean of investigator and centralized evaluation committee measurements, r = 0.08, P = 0.28). The mean difference was 8 +/- 20 g/m2 (P < 0.001). CONCLUSION: Early results of the LIVE study quality control showed that real-time 'live', centralized echocardiographic reading was not only feasible, but also useful for avoiding unquantifiable echocardiograms and overestimation of left ventricular mass index. Thus, real-time, centralized echocardiographic quality control should be recommended for multicenter studies of regression of left ventricular hypertrophy.

Adult↗
PubMed1998

Indapamide improves flow-induced dilation in hypertensive rats with a high salt intake.

OBJECTIVE: Spontaneously hypertensive rats (SHR) are sensitive to a high salt intake and we investigated the question of whether flow-induced dilation is affected by this type of diet, as flow responses are especially sensitive to small changes in extracellular sodium concentrations. METHODS: We evaluated the effects of a diuretic (indapamide, 1.5 mg/kg per day, 8 weeks) on four groups of SHR (n=42). One group was fed with a normal-salt diet (0.4%, control group, n=10), the second with a high-sodium diet (8%, n=12), the third with a high-sodium diet and indapamide (1.5 mg/kg per day, 8% salt, n=10) and the fourth group was fed with indapamide alone (1.5 mg/kg per day, n=10). The response to flow was studied in mesenteric resistance arteries (146+/-6.1 microm internal diameter, pressure 100 mmHg) cannulated in vitro in an arteriograph. RESULTS: The increase in mean arterial pressure (from 186+/-4 to 218+/-6 mmHg; P < 0.01) and heart weight: body weight ratio (3.48+/-0.09 versus 4.34+/-0.1 mg/g; P< 0.01) caused by the high salt intake was prevented by indapamide. A high salt intake significantly decreased flow-induced dilation (6+/-0.8 versus 10.7+/-1.2 microm dilation with a flow of 160 microl/min; P< 0.05), while indapamide significantly prevented the decrease in flow-induced dilation in high-salt SHR. Indapamide had no significant effect on flow-induced dilation in mesenteric resistance arteries from SHR with a normal-salt diet. CONCLUSIONS: Indapamide prevented the decrease in flow-induced dilation caused by a high-salt diet Therefore, indapamide might counteract the disturbance in sodium-sensitive flow sensor(s), through a diuretic effect.

Animals↗
PubMed1998

Low-dose antihypertensive therapy with 1.5 mg sustained-release indapamide: results of randomised double-blind controlled studies. European study group.

OBJECTIVE: In accordance with international recommendations on the need to decrease doses of antihypertensive drugs, a low-dose (1.5 mg) sustained-release (SR) formulation of indapamide was developed to optimize the drug's efficacy : safety ratio. The aim of this work was to evaluate the benefit of a low-dose diuretic by consolidating the efficacy and safety results of two clinical trials with a similar design. PATIENTS AND METHODS: Clinical data were obtained in two European randomized double-blind studies with 690 mild to moderate hypertensive patients (95 mmHg < or = supine diastolic blood pressure < or = 114 mmHg using a mercury sphygmomanometer) treated respectively for 2 and 3 months, with a mean age of 53 and 57 years, 44 and 57% males, mean supine diastolic blood pressure of 100.6 and 102.5 mmHg and mean supine systolic blood pressure of 161.0 and 164.5 mmHg. RESULTS: The first study, a dose-finding study with indapamide SR at 1.5, 2 and 2.5 mg versus placebo and the immediate-release (IR) formulation of indapamide, showed that the 1.5 mg dosage of the new indapamide formulation had an improved antihypertensive efficacy : safety ratio. The second study confirmed the equivalence of blood pressure reductions with 1.5 mg indapamide SR and 2.5 mg indapamide IR, and better acceptability with 1.5 mg indapamide SR, particularly in the number of patients with serum potassium levels < 3.4 mmol/l, which was reduced by more than 50%. The long-term efficacy of 1.5 mg indapamide SR was observed through a 9-month open-treatment follow-up to the second study. CONCLUSION: The 1.5 mg SR formulation of indapamide has an improved antihypertensive efficacy : safety ratio, which is in accordance with international recommendations for the use of low-dose antihypertensive drugs and diuretics in first-line therapy of hypertension.

Adult↗
PubMed1998

Twenty-four hour antihypertensive efficacy of indapamide, 1.5-mg sustained release: results of two randomized double-blind controlled studies.

The antihypertensive efficacy of a 1.5-mg sustained-release formulation (SR 1.5) of indapamide, a diuretic related to thiazide, has been pointed out by using conventional sphygmomanometric measurement 24 h after dosing in clinic, in two large European randomized, double-blind, controlled studies (2 and 3 months). One of these studies was then extended to 12 months, as a complementary open study. Quality-controlled ambulatory blood pressure monitoring (ABPM) data for a total of 216 patients from these studies are presented, including subgroups of hypertensives and responders. Indapamide SR 1.5 achieves an adequate 24-h blood pressure control by significantly reducing the 24-h, diurnal, and nocturnal blood pressures versus baseline, confirming the sphygmomanometric data. The benefit at 2 and 3 months is maintained at 1 year, which confirms the long-term efficacy of SR 1.5 mg. The trough-to-peak ratio--not previously calculated for a diuretic according to international guidelines--meets Food and Drug Administration requirements and confirms the 24-h efficacy of indapamide SR 1.5.

Adolescent↗
PubMed1998

High sodium intake decreases pressure-induced (myogenic) tone and flow-induced dilation in resistance arteries from hypertensive rats.

High sodium intake has been associated with a higher blood pressure level. Resistance arteries are the main determinants of blood pressure. They are largely regulated by pressure (tensile stress)-induced tone (myogenic tone, MT) and by flow (shear stress)-induced dilation (FD). Thus, we studied the effect of NaCl (8%) intake for 8 weeks on FD and MT in mesenteric resistance arteries of spontaneously hypertensive rats. Arteries were cannulated and mounted in an arteriograph. Intraluminal diameter was measured continuously. High NaCl intake increased mean arterial pressure (186+/-5 to 217+/-6 mm Hg, P<0.01). Passive arterial diameter ranged from 112+/-6 to 185+/-9 microm (pressure from 25 to 125 mmHg, no effect of NaCl). MT developed in response to pressure (tone from 89+/-1% to 83+/-3% of passive diameter, 25 to 125 mm Hg). High NaCl intake significantly decreased MT (89+/-1% versus 83+/-3% of passive diameter when pressure was 125 mm Hg, P<0.023). High NaCl intake also decreased FD (6.5+/-0.8 versus 10+/-1.3 microm dilation under a pressure of 100 mm Hg and a flow rate of 160 microL/min, P<0.012). Thus, high salt intake decreased both flow (shear stress)-induced dilation and pressure (tensile stress)-induced tone in mesenteric resistance arteries. These findings might reflect attenuation by NaCl of flow and pressure mechanosensor processes.

Analysis of Variance↗
PubMed1997

[A critical review of available tools for evaluating memory enhancers in Alzheimer's disease].

The study reviews critically the neuropsychological measurement tools available to assess the efficacy of potential memory enhancers in patients with Alzheimer's disease (AD). A review of some concepts concerning the characteristics of memory impairment in AD patients and of problems related to the selection of a study population provides a framework for this analysis. The tools available for efficacy evaluations are then classified according to their conceptual and formal characteristics: psychometric tests, rating scales and clinician global assessment tools. In each category the instruments were assessed according to several criteria: construct and ecological validity; sensitivity to changes in symptomatology; inter-rater reliability and the reliability of equivalent forms; feasibility for use with AD patients, especially brevity, to encourage their cooperation. Examining advantages, drawbacks and limitations of instruments in each category yields two conclusions: no single instrument scale or test battery fills all the criteria for a clinical trial, but these imperfect instruments are complementary. Accordingly, a battery including the three categories of instruments and allowing for investigation of the different memory systems has been proposed.

Alzheimer Disease↗
PubMed1997

Apolipoprotein E and Alzheimer disease: genotype-specific risks by age and sex.

The distribution of apolipoprotein E (APOE) genotypes as a function of age and sex has been examined in a French population of 417 Alzheimer disease (AD) patients and 1,030 control subjects. When compared to the APOE epsilon3 allele, an increased risk associated with the APOE epsilon4 allele (odds ratio [OR] [epsilon4] = 2.7 with 95% confidence interval [CI] = 2.0-3.6; P < .001) and a protective effect of the APOE epsilon2 allele (OR[epsilon2] = 0.5 with 95% CI = 0.3-0.98; P = .012) were retrieved. An effect of the epsilon4 allele dosage on susceptibility was confirmed (OR[epsilon4/epsilon4] vs. the epsilon3/epsilon3 genotype = 11.2 [95% CI = 4.0-31.6]; OR[epsilon3/epsilon4] vs. the epsilon3/epsilon3 genotype = 2.2 [95% CI = 1.5-3.5]). The frequency of the epsilon4 allele was lower in male cases than in female cases, but, since a similar difference was found in controls, this does not lead to a difference in OR between sex. ORs for the epsilon4 allele versus the epsilon3 allele, OR(epsilon4), were not equal in all age classes: OR(epsilon4) in the extreme groups with onset at < 60 years or > 79 years were significantly lower than those from the age groups 60-79 years. In epsilon3/epsilon4 individuals, sex-specific lifetime risk estimates by age 85 years (i.e., sex-specific penetrances by age 85 years) were 0.14 (95% CI 0.04-0.30) for men and 0.17 (95% CI 0.09-0.28) for women.

Age of Onset↗
PubMed1996

Antinociceptive effects of oral clonidine and S12813-4 in acute colon inflammation in rats.

Acute colonic inflammation was induced by perendoscopic injection of 50 microleters of dilute formalin (5%) in the depth of the colonic wall (c.w.) in rats. Compared to saline injection, the procedure was followed by nociceptive behaviors from which visceral nociception was quantified. The alpha 2-adrenoceptor agonist, clonidine 2-[2,6-dichlorophenylamine]-2-imidazole hydrochloride (75, 150 and 300 mg/kg), administered orally 15 min after c.w. injection of formalin significantly reduced the nociceptive responses at the high dose only. However, when administered 30 min prior to nociceptive stimulation, the compound exhibited an antinociceptive effect at the three doses. A novel analgesic, the compound "S12813-4' 3-[2-(4-phenylpiperazine-1-yl)-ethyl]-2-oxo-2,3-dihydro-oxazolo[b] pyridine, chlorydrate (10, 30 and 90 mg/kg), given orally displayed antinociceptive effects whatever the administration schedule, before or after c.w. injection of formalin. The antinociceptive effect of S12813-4 (30 mg/kg given orally) was prevented by subcutaneous (s.c.) injection of yohimbine or idazoxan (1 mg/kg). We conclude that visceral nociception elicited by formalin-induced colonic inflammation is attenuated by clonidine and S12813-4. The pharmacological profiles of the two compounds and the inhibition of the antinociceptive effect of S12813-4 by yohimbine and idazoxan suggest that noradrenergic mechanisms are involved in the transmission and/or modulation of the nociceptive influx arising from the inflamed colon.

Acute Disease↗
PubMed1996

Effect of indapamide on left ventricular hypertrophy in hypertension: a meta-analysis.

Left ventricular hypertrophy is a major risk factor for cardiovascular morbidity and mortality. Angiotensin-converting enzyme inhibitors, calcium antagonists, and beta-blockers prevent, and cause regression of, left ventricular hypertrophy after short-term therapy. The ability of diuretics to do the same is unclear. We have performed a meta-analysis of studies documenting the effect on left ventricular mass of 6 months' treatment with 2.5 mg indapamide daily. Six studies comprising 197 patients, aged 20-75 years, were included. There was an overall mean reduction in left ventricular mass index of 13.3%, which was principally due to a reduction in left ventricular wall thickness rather than internal diameter.

Adult↗
PubMed1996

Regression of left ventricular hypertrophy in patients with essential hypertension. Results of 6 month treatment with indapamide.

Left ventricular hypertrophy (LVH) is a major risk factor for cardiovascular morbidity in hypertensive patients. The effects of diuretics on LVH have raised controversies, but recent studies suggest that diuretics are able to reduce LVH in hypertensive patients, mainly through a reduction in ventricular diameter. The present multicenter open study was designed to test the effects of indapamide, a widely used nonthiazide diuretic, on LVH in patients with essential hypertension. Patients had to have mild-to-moderate essential hypertension (supine diastolic blood pressure [sDBP] 95 to 115 mm Hg) with echocardiographic evidence of LVH (left ventricular mass index [LVMI] > 130 g/m2 for men and > 110 g/m2 for women). After a 2 week placebo run-in period, eligible patients underwent a 6 month treatment with 2.5 mg indapamide daily. All echograms were performed by the same investigator before and after 6 months of indapamide. Clinical and biological acceptability and quality of life (visual analog scale) were also studied. One hundred and thirty patients were included in the study and 112 completed the trial. Indapamide induced a significant reduction i systolic and diastolic blood pressures. Indapamide induced a marked reduction in posterior wall thickness (from 12.1 +/- 2.0 to 11.2 +/- 1.6 mm) and in interventricular wall thickness (from 12.7 +/- 1.7 to 11.8 +/- 1.9 mm; each P < .001) and a slight decrease in left ventricular diameter (P = .049). This resulted in a 13% reduction in LVMI (from 161.9 +/- 37.9 to 140.7 +/- 33.8 g/m2, P < .001). Left ventricular fractional shortening remained unchanged. There was no significant relation between changes in LVMI and changes in systolic, diastolic, or mean blood pressure. No significant adverse clinical or biological effects were reported during the study. The increased score of the visual analog scale indicated that overall well-being was improved (P < .001). Our study indicates that indapamide, in addition to blood pressure control, is able to reduce LVH. This effect was achieved mainly through a reduction in wall thicknesses rather than in internal cavity diameter.

Adult↗
PubMed1996

Fixed-dose combination of perindopril with indapamide in spontaneously hypertensive rats: haemodynamic, biological and structural effects.

OBJECTIVE: The present study was designed to test the effects of chronic combined treatment with low doses of an angiotensin converting enzyme inhibitor (perindopril) and of the diuretic indapamide in spontaneously hypertensive rats (SHR). METHODS: Adult SHR were treated with placebo or increasing doses of the combination of the drugs (0.3, 1 and 3 mg/kg per day; ratio of doses 0.32). In a separate set of experiments, the effects of the drugs combined (1 mg/kg per day) was compared with those induced by each drug alone. RESULTS: The drug combination dose-dependently decreased systolic blood pressure and its hypotensive effect was more marked than those induced by each treatment administered alone (untreated 208 +/- 5 mmHg, indapamide 185 +/- 5 mmHg, perindopril 150 +/- 3 and the combination 123 +/- 7 mmHg). A 12-week treatment with the drug combination (1 mg/kg per day) was not accompanied by any change in diuresis or urinary excretion of Na or K. The same treatment decreased cardiac hypertrophy and collagen. At the vascular level, the drug combination decreased aortic, carotid and femoral media cross-sectional areas, as well as aortic and carotid collagen density. This latter effect was accompanied by a significant increase in carotid artery compliance assessed in vivo at constant pressure. Finally, in isolated aortae, chronic combined drug treatment was associated with an increased basal release of nitric oxide and a decrease in the hypertension-induced endothelium-dependent contractions in response to acetylcholine. CONCLUSION: These experiments suggest that chronic combined treatment with low doses of an angiotensin converting enzyme inhibitor and a diuretic such as indapamide may be of value in the treatment of hypertension.

Acetylcholine↗
PubMed1996

Effects of S-9977-2 on histamine levels in rats.

S-9977-2 is a new molecule with promnesic and antiamnesic properties. In this study, we investigated the effects of i.p. administration of S-9977-2 on histamine (HA) levels in several regions of the rat brain, and also in peripheral areas, using high performance liquid chromatography (HPLC) with fluorometric detection. S-9977-2 (0.025 mg/kg) induced an increase in the content of HA in the anterior hypothalamic region, with a significant effect 30 min after injection (1.77 +/- 0.36 nmol/g vs. 2.43 +/- 0.40 nmol/g; p < 0.01). It did not significantly modify HA levels in the posterior hypothalamic region, hippocampus, fronto-parietal cortex, blood, spleen, or adrenal glands. A clear tendency to increase HA content was observed in the hippocampus (0.16 +/- 0.03 nmol/g vs. 0.39 +/- 0.31 nmol/g, ns) and fronto-parietal cortex (0.55 +/- 0.45 nmol/g vs. 0.70 +/- 0.28 nmol/g; ns). S-9977-2 at doses of 0.005 and 0.125 mg/kg i.p. did not produce any significant change in HA levels in any of the samples tested 30 min after administration. The present results demonstrate that S-9977-2 increases HA levels in the anterior hypothalamus, which is the brain region with the highest content in histaminergic fibers. This fact suggests that the neuronal HA system might be involved directly or indirectly in the pharmacological actions of S-9977-2.

Adrenal Glands↗