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Biomedical subjects

G Chatellier

Publications and source records attributed to G Chatellier.

At least 163 records · Page 9Linked to original sources

Investigation of the biochemical effects of renin inhibition in normal volunteers treated by an ACE inhibitor.

1. In order to investigate accurately the biochemical effects of renin inhibition in man, we have developed a sensitive assay to measure angiotensin I (1-10) decapeptide. 2. Angiotensins were extracted from plasma by adsorption to phenylsilylsilica, and angiotensin I (Ang I) was quantified by radioimmunoassay. The detection limit was 0.77 fmol ml-1, and the extraction recovery of [125I]-Ang I added to albumin buffer was 83% at the inflection point (10 fmol ml-1) of the standard curve. The overall recovery was 98.5 +/- 3.5%. The intra- and inter-assay reproducibility was 10.4% and 9.7% respectively. Cross-reactivity of the antiserum used was low (less than 0.3%) with all angiotensin peptides tested except Ang (2-10) nonapeptide. 3. A human pharmacological model was subsequently used to assess in vivo the biochemical effects of the renin inhibitor CGP 38560A. Six healthy volunteers received 20 mg lisinopril, a long-acting ACE-inhibitor. During the following 24 h, the renin-angiotensin system was reset with typically elevated active plasma renin and Ang I, at respectively 275 and 429% of basal values. 4. In a randomized three-way cross-over protocol, the six volunteers received a 30 min infusion of the renin inhibitor CGP 38560A (125 or 250 micrograms kg-1) or 5% glucose. The fall in plasma Ang I was 92% and 97.5% after the lowest and highest dose of the renin inhibitor, respectively. A concomitant increase in active plasma renin was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Changes in levels of blood coagulation inhibitors in cirrhosis. Prospective study in 33 patients].

The variations of the main plasma inhibitors of coagulation were prospectively studied in 33 cirrhotic patients, of which 9 presented with hepatocellular carcinoma, 5 of those associated with portal vein thrombosis. The mean prothrombin index was 49 +/- 16 percent. All plasma values of inhibitors were diminished, but to varied degrees: the mean values were: protein C (PC): 33 +/- 15 percent, antithrombin III (AT III): 50 +/- 23 percent, total protein S (PST): 67 +/- 20 percent. The more severe the cirrhosis, the more decreased were the values of antithrombin II and protein C. According to Child classes A, B, and C, antithrombin III plasma values were 64 +/- 20, 50 +/- 21 and 26 +/- 11 percent and protein C values were 43 +/- 16, 32 +/- 8 and 19 +/- 9 percent, respectively. We were able to define expected plasma values of the plasma inhibitors as a function of coagulation factors during cirrhosis; AT III (percent) = 1.16 x factor II (percent) - 7.85; PC (percent) = 0.49 x AT III (percent) + 8.96; PC (percent) = 0.55 x factor II (percent) + 5.55; PST (percent) = 0.76 x factor II (percent) + 28.74. However those equations cannot be extrapolated to patients presenting with cirrhosis complicated with portal thrombosis.

Adult↗

[Left ventricular involvement in Conn adenoma, renovascular hypertension and pheochromocytoma before and after etiological treatment].

AIM OF THE STUDY: Assessment of left ventricular (LV) structural modifications following etiologic treatment of secondary hypertension, in a group of 43 patients. PATIENTS AND METHODS: M-Mode echocardiograms were independently analysed by 2 trained investigators before and 7.4 months (RV), 11 patients with COnn's adenoma (C) and 9 patients with phaeochromocytoma (PH). RESULTS: Age, sex ratio, antihypertensive treatment, and duration of hypertension before treatment were comparable among the 3 groups. Blood pressure was higher in C and RV than in PH for casual (C: 190/116; RV: 193/109; PH: 146/91; p < 0.01/0.05) as well as ambulatory blood pressure (C: 140/93; RV 153/89; PH: 126/80; p < 0.01/0.05). Before etiologic treatment, systolic function was normal in the 3 groups whereas LV mass index differed between the 3 groups (C: 147; RV: 118; PH: 85 g/m2). LV end diastolic diameter index was smaller in PH (26.4 mm/m2) than in C (29.1) and RV (28.8). After treatment, there was a significant reduction on office (C: -43/-20; RV: -39/-19; PH: -20/-12 mmHg) and ambulatory (C: -6.6/-5.6; R: -20/-9.9; PH: -4.7/- 4.5) blood pressure. Systolic function was not altered. LV mass index was significantly reduced in C and RV but not in PH (C: -18%; RV: -7%; PH: -5%). Changes in LV end diastolic diameter index were not significant (C: -2%; RV: 0%; PH: + 6%). There was no correlation between LV mass index changes and blood pressure differences. CONCLUSION: Etiologic treatment leads to significant regression of LV hypertrophy in patient with renovascular hypertension or Conn's adenoma, at least partly independently of blood pressure change. Humoral and volume factors may play a role in LV regression.

Adrenal Gland Neoplasms↗

Bayesian statistics as applied to hypertension diagnosis.

This paper deals with the following hypertension diagnoses: essential hypertension and five types of secondary hypertension: fibrodysplasic renal artery stenosis, atheromatous renal artery stenosis, Conn's syndrome, renal cystic disease, and pheochromocytoma. Only blood pressures, general information and general biochemical data are taken into account. Nineteen items were finally selected, by statistical investigation of experimental data, as being both discriminative and independent. The marginal density distributions of every item, and then joint density distribution functions were determined within six types of hypertension. The frequency of a given hypertension type within the hypertensive patients was used as prior probability of this state. The loss matrix was established by medical arguments. The expected loss corresponding to six possible decisions could thus be calculated for all cases. Both the ratio of secondary hypertensions that could be inferred from our set of data (not including the results of complementary tests) and that of correct "essential" hypertension diagnosis proved to be satisfactory.

Bayes Theorem↗

Renin release regulation during acute renin inhibition in normal volunteers.

Blockade of the renin-angiotensin system by an angiotensin converting enzyme (ACE) inhibitor or an angiotensin II (Ang II) antagonist is accompanied by a reactive rise in renin release. This rise is generally attributed to interruption of the short feedback loop between Ang II and renin release. Similarly, after the administration of a renin inhibitor, the plasma concentrations of active and total renin are increased and plasma renin activity is suppressed. The aim of the present study was to investigate if a fall in the plasma Ang II level is the unique determinant of the rise in the active renin (AR) level that follows renin inhibition. Six normal male volunteers participated in three successive 240-minute experiments at weekly intervals according to a single-blind randomized Latin square design. For experiment 1, Ang II was infused at 2 ng/kg/min from 0 to 60 minutes and at 4 ng/kg/min from 60 to 120 minutes. For experiment 2, 0.3 mg/kg of the new potent renin inhibitor Ro 42-5892 was injected at 30 minutes followed by infusion at 0.1 mg/kg/hr from 30 to 240 minutes. For experiment 3, Ang II and Ro 42-5892 were administered simultaneously at the same doses as described above. The mean +/- SEM Ang II concentration increased from 10.2 +/- 1.6 to 33.7 +/- 11.2 pg/ml after infusion of exogenous peptide. It decreased from 9.5 +/- 0.9 to 1.4 +/- 0.3 pg/ml after the injection of Ro 42-5892 and increased from 15.6 +/- 2.9 to 37.1 +/- 11.8 pg/ml after the simultaneous infusion of both compounds.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗

[Reproducibility of Doppler measurements in renal circulation].

Duplex ultrasonography is now used to detect renal artery (RA) stenosis, but measurement reproducibility was not assessed systematically in renal circulation. Our aim was to definite intra and inter-observer variabilities of initial acceleration time (AT), peak systolic velocity (SV), and end-diastolic velocity (DV) in RA. We examined 12 hypertensive patients with angiographically normal RA and 2 normotensives. During these 14 explorations, all measurement were made by the operator A twice, and 13/14 times by the operator B twice. A duplex ultrasound CGR Radius CF* device was used with a 3.75 MHz probe. Once the RA spotted by color imaging, AT, SV, DV were measured by pulsed doppler aligning on arterial axis without angle correction with translumbar approach at different levels (distal trunk, hilus, sinus). SV intra-observer variabilities were for operator A on mean 30% at distal trunk, 3% at hilus, 4% at sinus; for B, there were respectively 16, 0, 2%. About DV, there were for A 3, 0, 1% and for B 2, 7, 0%. Reproducibility was worse about AT. SV inter-observer variabilities were 14, 2, 3%, for DV 13, 3, 2%, for AT 2, 6, 5%. Therefore indexes based on SV, DV, and AT with a less reproducibility may be used for screening or follow-up, but their diagnostic value is still to assess.

Adult↗

[Creatinine levels in polycystic kidney disease complicated by arterial hypertension. Role of blood pressure control].

As hypertension often precedes renal failure in polycystic kidney disease, it has been suggested that efficient blood pressure control could slow down the progress of the disease. To test this hypothesis, we made a retrospective study of 32 hypertensive patients with familial polycystic kidney disease who had been followed up for an average period of 75 months (range: 20 to 168 months). We examined the relations between creatinine levels or the slope for their increase with time on the one hand, and the mean blood pressure measurements recorded during the surveillance period on the other hand. For the group of 32 patients as a whole, there was no significant correlation between creatinine levels or their variations and blood pressure or its variations. The 13 patients whose creatinine levels rose by more than 50 p. 100 did not differ from the 19 others as regards age, known duration of hypertension, initial or final blood pressure or the number or nature of the antihypertensive drugs they received. This preliminary investigation does not rule out the existence of a link between blood pressure control and the maintenance of renal function during polycystic kidney disease complicated by hypertension, but it does suggest that any such link is tenuous.

Adult↗

Tacrine (tetrahydroaminoacridine; THA) and lecithin in senile dementia of the Alzheimer type: a multicentre trial. Groupe Français d'Etude de la Tetrahydroaminoacridine.

OBJECTIVE: To see whether combined treatment with oral tacrine (tetrahydroaminoacridine; THA) and lecithin improves the symptoms of patients with Alzheimer's disease. DESIGN: Multicentre double blind, placebo controlled, random order crossover trial with individual determination of maximum tolerated dosage and four month follow up. SETTING: Outpatient departments at six university neurological centres. PATIENTS: 67 Outpatients (24 men, 43 women) aged 53-81 (mean 66 (SD 7.3)) selected according to the following criteria: probable Alzheimer's disease as defined by the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association; absence of mood disorder; mini mental state score lower than 26; availability of a close relative able to complete questionnaires; and informed consent of the patient or his or her closest relative, or both. INTERVENTIONS: Mean of 114 mg tacrine or placebo daily plus 1200 mg lecithin daily given in three divided doses for one four week active treatment period and one four week control period without washout at crossover. MAIN OUTCOME MEASURES: Cognitive state as assessed by Folstein's mini mental state rating scale, behavioural state as assessed by the Stockton geriatric rating scale, and overall state as assessed with a visual analogue scale rated by both the relative and the physician. RESULTS: Compared with placebo tacrine did not improve either the mini mental state score (mean 14.9 (SD 7.3) v 14.8 (7.3)) or the Stockton geriatric score (28.2 (15.7) v 28.7 (17.8)), but a slight and statistically significant improvement occurred in the physician's score on the visual analogue scale (6.3 (10.2) v 11.6 (17.9)). Seven patients dropped out. Six patients were excluded because of acute hepatitis and one withdrew for personal reasons not related to treatment. Two other patients developed acute hepatitis at the end of the eight week crossover trial and another during the follow up study. Twenty patients complained of gastrointestinal side effects. CONCLUSIONS: Neither short term nor long term treatment with oral tacrine at dosages lower than 125 mg/day improves the symptoms of Alzheimer's disease. Moreover, these dosages may induce hepatitis (nine of 67 patients in this series).

Aged↗

Embryotoxic effects of sodium arsenite and sodium arsenate on mouse embryos in culture.

Embryotoxic effects of two inorganic arsenic compounds, sodium arsenite (Asi) and sodium arsenate (Asa), on the development of mouse embryos during early organogenesis were studied using the whole embryo culture technique. Embryos with three to five somites exposed to 1-40 microM Asi or to 10-400 microM Asa were cultured for 48 hours and their development was compared with that of control embryos. Asi proved to be teratogenic between 3 and 4 microM and embryolethal at higher concentrations; Asa had similar activity but at concentrations ten times higher than for Asi. Both compounds produced a growth retardation and a similar pattern of defects. Growth retardation was indicated by a statistically significant reduction in crown-rump length, head length, and yolk sac diameter. Abnormal embryos were characterized by hypoplasia of the prosencephalon with open neural tube, hydropericardium, somite abnormalities, and failure of development of limb buds and sensory placodes. These results confirm that both Asa and Asi are embryotoxic compounds and that the Asi activity occurs at concentrations ten times lower than for Asa. Our results suggest that in humans both of these compounds may be involved in part of "unaccountable" early abortions and malformations claimed to be due to the toxicity of heavy metals.

Animals↗

Intracranial meningiomas in elderly patients. Postoperative morbidity and mortality. Factors predictive of outcome.

We studied retrospectively a series of 96 patients (36 men, 60 women), older than 65 years of age (mean age: 70 +/- 4 years, range 65-82), operated upon for an intracranial meningioma from October 1978 to December 1988. Fifty-two patients (54%) were under 70, 32 between 71 and 75 and 12 over 75 (46%). The tumours were diagnosed for all the patients by CT scan. Thirty-four (35%) were located over the convexity, 24 (25%) in the falx/parasagittal region, 38 (40%) in the base, tentorium and posterior fossa. Neurological and physical conditions were assessed preoperatively and at the closing date in June 1989. Operative mortality was 16% (15/96). Patients were divided into two groups: poor outcome, defined by the death or a post-operative Karnofsky index less than or equal to 70 (n = 36), and good outcome defined by a Karnofsky index of 80 or more (n = 60). The two groups did not differ regarding age, sex ratio, tumour size and peritumoural oedema. The only predictors of poor outcome were poor preoperative general health condition (stage III of the American Society of Anesthesiology classification), (p less than 0.01), poor preoperative neurological condition (Karnofsky's index) (p less than 0.001), and location of the tumour on the base or in posterior fossa (p = 0.02).

Aged↗

Lp(a) levels in different types of dyslipidemia in the French population.

The serum lipoprotein Lp(a) concentration was measured in 1065 individuals in order to assess whether there was a relation between the type of dyslipidemia and the level of Lp(a). Males and females, aged between 2 and 83 years old, were included in the study. Quantification was performed by an immunonephelometric technique. The whole population was divided into normolipidemic (NL), type IIa without xanthoma (type IIa), type IIa with xanthoma (FH), type IIb and type IV phenotypes. Lp(a) level was arbitrarily divided into 5 subclasses in each group of dyslipidemia and in the normolipidemic group. In addition each group was divided according to sex and whether or not they were under treatment. We observed a significant difference between the median Lp(a) level of the normolipidemic group (NL) and of the dyslipidemic group as a whole. Median Lp(a) levels in the 4 dyslipidemic groups did not differ significantly. Sex, age and treatment did not influence the distribution of Lp(a) values distribution. Only weak correlations (Spearman's rank test) were observed between Lp(a) and other lipid parameters (total cholesterol, LDL, apo B, HDL, triglycerides): the highest correlation (r' = 0.15) was between Lp(a) and apo B. We conclude that Lp(a) level is not influenced by the type of dyslipidemia, sex or hypolipidemic drugs.

Adolescent↗

Effects of captopril and minoxidil on left ventricular hypertrophy in resistant hypertensive patients: a 6 month double-blind comparison.

In a double-blind 6 month trial, the cardiac effects of captopril and minoxidil, administered as third step treatments, were compared in 34 men with essential hypertension and diastolic blood pressure greater than 95 mm Hg who were taking 200 mg/day of metoprolol and 80 mg/day of furosemide. Average daily doses of captopril and minoxidil were 269 mg (range 150 to 300) and 20 mg (range 7.5 to 30), respectively. At the end of the 6 months' treatment, blood pressure had dropped significantly in both groups, but echocardiographic criteria of hypertrophy improved only in the captopril group (intragroup comparison): blood pressure, thickness of the intraventricular septum and posterior wall, and the left ventricular mass index, respectively, decreased from 163/102 to 135/89 mm Hg (p less than 0.001), 17.4 to 15.9 mm (p less than 0.05), 14.5 to 13.4 mm (p less than 0.05) and 236 to 198 g/m2 (p less than 0.001). In the minoxidil group, blood pressure dropped from 160/99 to 137/87 mm Hg (p less than 0.001), but echocardiographic criteria were not significantly modified. Fractional shortening remained normal in both groups. These results show that in patients with severe left ventricular hypertrophy, captopril-based triple therapy reduces left ventricular mass without altering systolic performance, whereas minoxidil-based therapy does not.

Adult↗

Computer-assisted techniques for evaluation and treatment of hypertensive patients.

An integrated approach, progressively implemented in the ARTEMIS system since 1975, is described for the computerized management of hypertensive patients. From a medical point of view, computerized programs can be used to memorize patients' individual records and profiles, to facilitate patient management and follow-up, to store medical knowledge about hypertension and to provide facilities for decision making at the level either of the individual patient or of the population followed up. From a technical point of view, the methodology used integrates data and knowledge management facilities into the same software. Five hypertension clinics are presently using the system in France and more than 22,000 records have been registered. Answer rates to 12 mandatory questions regarding past history and examination at first visit were superior to 95% in 19,601 records created between January 1976 and December 1987. Patient database interrogation can be used to evaluate the sensitivity and specificity of various signs and symptoms for the diagnosis of secondary hypertension, and to predict, for each patient, his/her cardiovascular risk, the risk of drop-out, the risk of insufficient blood pressure control and the probable blood pressure level. It also serves to test the content and validity of the associated expert system which is progressively built up. A prospective evaluation of the performance of the expert system on 80 cases of hypertension showed overall agreement between the specialists and the expert system ranging from 58 to 91% depending on the decision.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Treatment of malignant gliomas with surgery, intra-arterial infusions of 1-(2-hydroxyethyl)chloroethylnitrosourea, and radiation therapy: a phase II study.

Forty patients with malignant supratentorial gliomas were treated with surgery, intra-arterial infusions of 1-(2-hydroxyethyl)chloroethylnitrosourea, and radiation therapy. The median duration of survival was 12 months; it differed according to the histological subtype (over 30 months for patients with anaplastic astrocytomas or anaplastic oligodendroglioma and 10.5 months for glioblastoma; P = 0.0025). Serious complications of monocular blindness and leukoencephalopathy were observed in four patients (10%).

Adolescent↗

[Value and limits of renal artery examination in the aged].

We compared the efficacy and safety of percutaneous renal angioplasty for the treatment of renovascular disease in younger (aged less than 60) and elderly patients (aged 60 or more). Angioplasty yielded a higher technical success rate in younger patients while complications occurred more frequently in the elderly. Among patients with a successful angioplasty, the rate of cure or improvement of hypertension tended to be higher in the younger patients. The efficacy and safety of renal artery angioplasty may be limited in elderly patients by age-associated atheroma of renal and extra-renal arteries.

Aged↗