Higher frequency of genetic variants conferring increased risk for ADRs for commonly used drugs treating cancer, AIDS and tuberculosis in persons of African descent.

There is established clinical evidence for differences in drug response, cure rates and survival outcomes between different ethnic populations, but the causes are poorly understood. Differences in frequencies of functional genetic variants in key drug response and metabolism genes may significantly influence drug response differences in different populations. To assess this, we genotyped 1330 individuals of African (n=372) and European (n=958) descent for 4535 single-nucleotide polymorphisms in 350 key drug absorption, distribution, metabolism, elimination and toxicity genes. Important and remarkable differences in the distribution of genetic variants were observed between Africans and Europeans and among the African populations. These could translate into significant differences in drug efficacy and safety profiles, and also in the required dose to achieve the desired therapeutic effect in different populations. Our data points to the need for population-specific genetic variation in personalizing medicine and care.

High lead level in the Alps in XIXth century, learning from the analysis of 138 historical hair stands.

Analysis of hair is known to provide useful information about environmental and toxic exposures. Very little historical use has been made of this type of investigation. Here we study 138 human hair samples from 19th century in France. In order to examine the potential association between contamination and historical health impacts, we characterized contamination by 33 elements in a set of hair strands sampled during the last quarter of the 19th century in the Savoy region of France. After a selected washing step on 138 hair strands conserved at the Museum National d'Histoire Naturelle in Paris (France), we assessed the presence of inorganics by ICP/MS, and lead level was higher than values reported in literature. We then compared concentrations and distributions between women and men, sampling locations and crossing gender and geographical origin. Hair lead level was high throughout Savoy at the end of the 19th century: significantly higher for people living in towns or industrial valleys, and lower for those of countryside and mountains areas. Environmental and economic changes (industrialization and urbanization with water adduction and leaded paints), living habits (kitchenware, cosmetics, wine, and tobacco), and local features (mines exploitation, railroad development, and industrialized narrow valleys) could be envisaged for explaining the level of lead contamination. In the same period, the two main industrial valleys of Savoy (Maurienne and Tarentaise) had high rates of endemic goiter and cretinism and among the highest hair lead levels. Other lines of evidence will need to be explore to investigate a possible link between historical Pb exposure and goiter in the study area.

The mandible of Saint-Louis (1270 AD): Retrospective diagnosis and circumstances of death.

INTRODUCTION: Recent paleopathological cases have shown the usefulness of interdisciplinary odontological studies in the investigation of historical figures. OBSERVATION: A macroscopic examination of the mandible of Saint-Louis (13th c. AD), conserved in the cathedral of Notre-Dame (Paris, France) was carried out, and compared with biographical data about the life and death of the King, and contemporaneous cases of infectious/inflammatory diseases. We found post-mortem tooth loss associated with moderate signs of infectious and inflammatory diseases, which precise diagnoses are discussed facing historical chronicles and sources: main diagnosis is scurvy, potentially associated with bacterial infection. DISCUSSION: Our results support the identification of the relics, and improve the knowledge about the saint's circumstances of death related to metabolic deficiencies and infections.

Massive overfeeding and energy balance in men: the Guru Walla model.

To determine the magnitude of the thermogenic response to a massive long-term overfeeding, an energy-balance study was carried out in nine lean, young Cameroonian men participating in a traditional fattening session: the Guru Walla. Food intake, body weight, body composition, activity, and metabolic rates were recorded during a 10-d baseline period and over the 61-65 d of fattening. Total energy expenditure (TEE) was measured by using doubly labeled water during the baseline period and the final 10 d of Guru Walla. Cumulative overfeeding consisted of 955 +/- 252 MJ (chi +/- SD) mainly as carbohydrate. Body-weight increase was 17 +/- 4 kg, 64-75% as fat. Metabolic rates increased but TEE did not. However, when accounting for the reduction in physical activity, substantial thermogenesis was observed but its amplitude was not greater than that observed under less extreme carbohydrate-overfeeding conditions. If luxuskonsumption does exist, it is not related to the magnitude of the cumulative overfeeding.

General considerations on endemic treponematosis in the rural Sahel region of Upper Volta.

A sero-immunological survey conducted by indirect immunofluorescence technique has made it possible to determine accurately the prevalence and distribution of treponematoses in the Sahel rural region of Upper Volta. The number of carriers of antitreponemal antibodies varies from one place to another, but is particularly high in a nomad community, where prevalence attains 84.2%. The magnitude of endemic foci can also be expressed in terms of maximal titer and geometric mean of antibody titers. The seropositive values increase as a function of age, but sex is not a significant factor as regards prevalence, which would appear to depend essentially on the way of life, habits and promiscuity.

[Rubella epidemiology in rural Upper Volta]. / Contribution à l'étude de l'épidémiologie de la rubéole en milieu rural voltaïque.

A survey aiming at evaluating the proportion of the female population aged 0-29 years, with a positive anti-rubella antibody titer, was carried out in two Upper-Volta villages, representative of the Sahel (Oursi) and the Savannah (Donsé) biotopes. A technique of inhibition of haemagglutination was used and 40 or more was considered as a positive titer. Seventy per cent of 230 serums were positive, all ages confounded. The proportion positive was 96% in the age group 12-18 years and 76% in the age group 19-29 years. Extrapolating these findings to the Upper-volta rural population we estimated the risk of congenital infection to justify the decision against or in favour of a vaccination campaign. On the basis of our results, it is suggested that rubella has low priority in public health planning in rural Upper-Volta and that mass vaccination is at present not justified.

New meta-analysis of treatment trials of hypertension: improving the estimate of therapeutic benefit.

The objectives of this sub group meta-analysis on the treatment of hypertension was to: (1) high-light specific results of well-designed trials; (2) group trials according to their specific clinical context; (3) express results of the meta-analysis in absolute reduction terms; and (4) estimate the bias of withdrawal because of blood pressure increase. This meta-analysis is based on summarised published results from randomised controlled trials, comparing a drug treatment versus placebo or no treatment, with morbi-mortality as the principle outcome. The following data were analysed: (1) total mortality; (2) cardiovascular mortality; (3) stroke; (4) major coronary events; and (5) congestive heart failure. The treatment significantly reduced the incidence of all outcomes in trials involving older patients, avoiding up to nine strokes (OR = 0.66, 95% Cl: 0.56-0.77) and four major coronary events (OR = 0.79, 95% Cl: 0.68-0.92) every 1000 patient-years when the bias of withdrawal was taken into account. The only outcome significantly influenced by treatment in younger patients with mild-to-moderate hypertension was stroke, with one stroke avoided every 1000 patient-years (OR = 0.51, 95% Cl: 0.39-0.66). There was insufficient statistical power in the trials which enrolled patients with non-moderate hypertension to reach clinical significance, except for the reduction in the incidence of congestive heart failure. However, the results indicated a trend towards greater absolute benefit under treatment. Trials enrolling patients with post-stroke hypertension also had insufficient power, but suggested benefit by the reduction of the incidence of stroke recurrence and congestive heart failure under treatment. In conclusion, the most constant treatment benefit concerned stroke, although the absolute reduction was very modest in younger patients with mild-to-moderate hypertension. Only the results from trials in older patients showed a significant reduction of major coronary events. Such results need further analyses, ideally based on individual patient data.

[Hypertension refractory to treatment. Case-control study]. / Hypertensions réfractaires au traitement. Etude cas-contrôle.

From a clinical population of 1290 subjects consecutively hospitalized between oct. 1969 and dec. 1976, 343 were re-examined at least three times during the four subsequent years, and their blood pressure at the 2nd and 3rd re-examinations were averaged (BPfu). Two types of refractory hypertensive were arbitrarily defined; type A: 58 subjects whose BPfu was greater than or equal to 200 and/or 120 mmHg, and type b: 53 subjects whose BPfu was greater than or equal to 107,5% of the average BP during the first four days of the initial hospitalisation. Two case-control studies showed that type A cases had initially significantly more severe hypertension (higher systolic and diastolic BP, and for the same BP, more severe cardiac and retinal involvement) than the controls; the mortality in 8,7 years reached 36%, for the cases and only 18% for the matched controls (p less than 0,05). Two similar case-control studies showed that type B cases had initially significantly lower systolic and diastolic BP, were significantly less treated and more prone to side-effects; the mortality in 8,9 years reached 25,6% for the cases, and 20,5% for the matched controls (n.s.).

[The Lyons Hypertension Control Program (1972-1978). Community analysis]. / Le programme lyonnais de lutte contre l'hypertension (1972-1978). Analyse communautaire.

A Community Control Program of Hypertension was undertaken in Lyon, as part of a WHO program. It dealed with two occupational, Study (S) and Reference (R), communities, each amounting to about 12,500 subjects. Its goal was to improve the level of treatment of hypertension in S, by stimulating the usual health care system without modifying it. It began in 1972 by a baseline total survey of both communities. Its aim was to check that the percentage of treated hypertensive subjects (HT) was the same in S and R (respectively 10.9% and 11.7%, n.s.), and to detect all HT's (subject being given an antihypertensive drug treatment, and/or BP greater than or equal to 160 and/or 94, or greater than or equal to 150 and/or 90 before age 30). The S intervention involved: detection of "new HT's" during the whole program; information of HT's, and referral to the treating physician of their choice, who was informed about the aim of the program and received later periodic information about hypertension management; periodic follow-up reconvocations. A leaflet including advices for C-V prevention was distributed to the whole S community in 1976. Evaluation was performed by a terminal total survey of both communities, from 1977 to 6/1978 (examination rates: 94.4 and 91.6% in S and R). The evaluation involved two analysis of 1977 data. -Cohort analysis (reported before): the percentage of treated HT's in the cohorts of 1972 HT's, still present in the community and hypertensive, was higher in S (63.0) than in R (46.1) (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

[Case-controlled study of the prognosis of cardiac insufficiency in treated hypertensive patients]. / Etude cas-contrôle du pronostic de l'insuffisance cardiaque chez l'hypertendu traité.

The aim of this study is to compare the long-term mortality of hypertensive subjects (HT) hospitalized with early heart failure (HF), and HT control without HF. The study is based on a population of 2,050 HT consecutively hospitalized for the first time for high blood pressure, between oct. 1969 and nov. 1983. Among them, 115 presented with early HF (symptoms for less than 3 months, the diagnosis being made mainly on interview data, physical exam, and radio); they were matched with Controls (C) belonging to the same hypertensive population, on the following criteria: same sex, same age (+/- 3 years), same date of entry (+/- 3 months), no HF at entry, 94 Cases (CHF) could be matched: 64 men and 30 women (mean age: 50 +/- 11). A mortality survey was done in April 1985, with response rates of 96 p. 100 (CHF) and 98 p. 100 (C). The mean follow-up period was 11 years. At entry, CHF differed highly significantly form C in many ways, and mainly in higher systolic BP, more frequent ECG changes (LV voltage, J-ST-T changes), more severe fundus oculi changes. The survival rate was assessed by life-table method. As a whole, it was significantly reduced in CHF vs C (p/0.005); the 10-years survival rates were respectively 51% (CHF) and 71% (C). Case-control comparison was examined for both sexes, and after division by the median age (50 years): CHF survival was significantly reduced in women, and in subjects aged 50 and more (p/0.03); no significant difference was observed for men and before 50. CHF were dichotomized for each available item at entry, and lifetable comparison was compared in both issuing sub-groups; no significant difference was observed, but for the age, with a better survival in youngest subjects (p/0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

[Prognostic value of serum creatinine in treated hypertensives. A case-controlled study]. / Valeur pronostique de la créatininémie chez l'hypertendu traité. Etude cas-contrôle.

UNLABELLED: The aim of the study was to assess the prognostic value of serum creatinine (SC), in treated hypertensive subjects (HT). In a clinical population of 2738 HT consecutively examined between october 1969 and december 1982, as in-patients (n = 1599) or out-patients (n = 1139): 152 had a moderate elevation (ME) of SC: below 178 USI but above the "normal limit" (124 USI in men, 106 USI in women); 95 had a severe elevation (SE) of SC: above 17 USI. Whenever possible, each of these cases was matched to a control, belonging to the same population: same sex, same age (+/- 5 years), same group (in-patient or out-patient), same date of initial examination (+/- 6 months), but normal SC. 119 ME and 63 SE could be matched. The response rate of the mortality survey (november 1985) was 100 per cent. The mean follow-up period was 10 years (range 3 to 16 years). RESULTS: At initial examination, ME and SE cases differed significantly from their controls in several variables (mainly: more frequent T or J-ST ECG abnormalities and stage III-IV retinal changes); The life-table survival rate was moderately and non significantly reduced in ME cases (57 per cent at 10 years vs 66 per cent in controls); this decrease was only observed and significant (p less than 0.001) in subjects aged 60 to 79 years. In SE cases, survival rate was markedly reduced (43 per cent at 10 years vs 73 per cent in controls, p less than 0.001) and this reduction is observed at least since the age 40.(ABSTRACT TRUNCATED AT 250 WORDS)

[Prediction and prognosis of diabetes incidence in treated hypertensive patients]. / Prédiction et pronostic du diabète incident chez l'hypertendu traité.

The study is based on a clinical population of 1962 hypertensive men and women consecutively examined as in- or out-patients in our clinic from Jan. 1967 to Dec. 1976. Those having a diabetes (treated for diabetes, or fasting glycemia greater than or equal to 7.75 USI) at initial exam were excluded. In february 1977, all were contacted by mail. 89 p. 100 of the subjects still living at the same address answered. 74 "cases" had developed a diabetes (clinical diagnosis, or fasting glycemia greater than or equal to 9.5 USI); they were matched with "controls" according to sex, age (+/- 2), and date of entry (+/- 4 months); all the controls had answered that they were not diabetic in Feb. 1977. At initial exam, the following abnormalities were significantly more pronounced in cases than in controls (by decreasing level of significance): glycemia 1 h. after glucose load, weight index (W/H2), fasting glycemia (p less than 0.001); ECG abnormalities of T (Minnesota code 5.1-3), and J-ST (4.1-3) (p less than 0.01); angina (p less than 0.05). Incidence of diabetes was studied in the basal population, by life table method, according to two abnormalities: relative weight greater than or equal to 115 p. 100, glycemia after load greater than or equal to 8.33. At five years, the estimations were: 0 p. 100 in both sexes, when both abnormalities were absent; 20 p. 100 in men and 31 p. 100 in women when both abnormalities were simultaneously present; 4 p. 100 in men and 2 p. 100 in women in other cases.(ABSTRACT TRUNCATED AT 250 WORDS)

[Estimate of the frequency of excessive diagnosis and treatment of hypertension]. / Une estimation de la fréquence des diagnostics et traitements abusifs de l'hypertension.

The ALPHA program aimed at testing the feasibility and the efficiency of a multifactorial, primary preventive intervention for cardiovascular diseases. It dealt with two occupational populations: intervention and control (without any randomization), each amounting to about 12,000 people. Largely because of the economic crisis, only 9,598 and 9,558 people were seen at the 1976 initial examination, and only 43 per cent of these were re-examined at the 1981-82 final examination. In 1976, there were some significative differences between the two populations (more smokers, and less anti-hypertensive treatments in the intervention group). The same differences were found in 1981-82. So the intervention was not proved efficient, and the two populations could be pooled for the present analysis restricted to the french people (to diminish the risk of misunderstanding), aged 20-59 at the initial 1976 examination. We used the following (arbitrary) criteria of hypertension: being treated for hypertension, and/or two BP readings at 160 and/or 94 mmHg at a few minutes interval. 1) In 1981-82, 659 men and 492 women answered that they were still treated for hypertension, and/or had been previously said that they had hypertension or too much blood pressure. At this 1981-82 examination, 298 of these men (45 per cent) and 294 of these women (58 per cent) did not meet the criteria of hypertension. 2) In 1976, 3,114 men and 2,429 women did not meet the criteria of hypertension. At the 1981-82 examination, they were asked whether they had had any antihypertensive treatment previously given. 139 were still under antihypertensive treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

[Comparison of hospitalized hypertensive patients and those consulting in a specialized unit. Initial clinical state and patient compliance]. / Comparaisons des hypertendus hospitalisés et consultants dans une unité spécialisée. Etat initial et observation des conseils médicaux.

This study is based on a series of 1919 hypertensive patients examined consecutively either in hospital or in the out patient clinic between 1969 and 1977 and reviewed in February 1977 by a postal questionnaire. The initial presentation of in-patients and out-patients differed very significantly in the same specialised department: the patients hospitalised were seen at a more advanced stage of their hypertensive illness. Neither group was truly representative of the general population of hypertensive patients. The percentage of patient compliance was only slightly lower in the out-patients. The mortality rate observed did not differ significantly from the expected mortality rate in out-patients; despite treatment it remained over 200% greater in the hospitalised group. It would seem desirable to develop out-patient rather than in-patient hospital facilities for the treatment of hypertension, despite the foreseeable practical difficulties.

[Value and role of echo-Doppler in the screening of renovascular hypertension. A prospective study of 144 arteries with reference to angiography]. / Intérêt et place de l'écho-Doppler dans le dépistage des hypertensions réno-vasculaires. Une étude prospective portant sur 144 artères, en référence à l'angiographie.

The purpose of the study is a rigorous validation of different ultrasonic criteria of renal artery stenosis, and the presentation of the performances of duplex sonography in renal artery stenosis screening. Sixty seven patients have been investigated by ultrasonic techniques, and the results of duplex compared with intraarterial or intravenous digital subtraction angiography. Two kinds of ultrasonic investigations have been defined: complete explorations when the renal artery ostium is accessible, incomplete explorations in other cases. The main difficulty preventing the exploration from being complete is obesity: all patient with an overweight of more than 20% of their theoretical weight have an incomplete exploration of at least one of their renal arteries. Furthermore, duplex sonography was not able to demonstrate polar artery in any case. When the exploration is complete, maximum systolic frequency (F max) recorded on the renal artery course, and the systolic frequency ratio of renal and aortic recordings (RAR) are two valuable criteria of significant stenosis (> 50%): mean difference between normal and stenosed arteries for these two variables is statistically significant (p < 0.01). To obtain a good specificity, pathological threshold have been fixed at F max > 3,500 Hz and RRA > 2.5. When the exploration in incomplete, ascending time (asc. T) and resistance index (RI) of doppler recording obtained in the renal hilum are two valuable criteria for severe stenosis (> 80%), or occlusion: the mean between stenosed and non stenosed arteries is statistically different (p < 0.001 and p < 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

[Primary prevention of hypertension in the general population. The Lyon Action for the Prevention of Hypertension and Atherosclerosis]. / Prévention primaire de l'hypertension artérielle dans la population. L'action lyonnaise de prévention de l'hypertension et de l'athérosclérose.

UNLABELLED: The aim of ALPHA (1976-1982) was to realize an action of cardiovascular prevention in a professional population, by combining a) an education of the general population and b) an individual managing of the high risk people. The "Study" (S) population originated from Lyon; the "Reference" (R) population originated from two smaller cities. There was no randomization. The plan of the study included: A baseline cross study, dealing respectively with 9,598 and 9,558 subjects in S and R; The educational intervention, aiming chiefly at reducing caloric and sodium intakes, and at increasing the potassium intake; The evaluation was done after five years, by re-examining the subjects seen at the baseline study and still present in the enterprises. Mainly because of the economic crisis, the re-examination rates were only about 45%. RESULTS: at the baseline, BP's were not significantly different: 137/77 S vs 132/75 R for men, and 129/74 S vs 126/73 R for women. The final comparisons about primary prevention of hypertension were computed after adjustment for age and sex, after exclusion of the subjects who were hypertensive at baseline. The knowledges about hygiene were significantly but moderately better in S. The urinary Na/K and Na/Creatinine ratios did not differ significantly. The alcohol intake was lower in S (p less than 0.001). The incidence of HT was greater in S (p less than 0.001). The means of the individual variations of systolic and diastolic BP were computed: the adjusted differences S-R were respectively + 1.53 and 2.19 mmHg for systolic and diastolic (p less than 0.001 for both). CONCLUSION: the feasibility of the intervention was moderate. The failure to demonstrate any prevention of HT might indicate that the hypothesis was wrong, and/or that the methodology was inadequate.

[The renin-angiotensin system and the sympathetic nervous system in essential hypertension]. / Système rénine-angiotensine et système nerveux sympathique dans l'hypertension artérielle essentielle.

In 112 patients with essential hypertension (HTA), free of any therapeutic and receiving the standard ward, a significant inverse relationship was found between age and plasma renin activity (PRA) and plasma aldosterone (PA), measured in the supine and upright position. Urinary epinephrine and norepinephrine were not related with age. When dividing the patients in 4 different age groups, it appeared that those younger than 30 years exhibited a significantly higher PRA and PA values and a higher frequency of borderline hypertension (45 p. 100) than the older ones (12 p. 100). So as to determine the characteristics associated with borderline HTA, it was necessary to eliminate the influence of age. This was achieved by comparing two groups of carefully age-matched patients, one with borderline HTA and the other with stable HTA. The only significant difference found was a significantly more marked increase in PRA in response to orthostatism, in patients with borderline HTA. Since renin responses to an orthostatic stress are largely mediated by renal nerves, this result suggest that borderline HTA could be associated with an increased reactivity of the sympathetic nervous system.

[Sports and blood pressure: association in a population of wage-earners]. / Sport et tension artérielle: association dans une population de salariés.

In a cross-sectional epidemiological survey, we examined the association between the practice of sports and blood pressure (BP). The study included 3,388 male employees (representing 90.1% of the target population) who were questioned about their habitual sports activity, in terms of average duration per week and intensity. The proportion of subjects who stated to engage in sports activity decreased with age, from 50.9% in the age class 20-29 years to 16.4% in the age class 50-59 years. We found a negative relationship between both systolic and diastolic BP and the weekly duration of sports activity. However this association increased with age and reached the statistical significance only in the age classes 40-49 years and 50-59 years (p less than 0.01 and p less than 0.001, respectively). Similar results were obtained when intensity of sports was used instead of duration. In order to test the independence of the observed association, the duration of sports activity (hours/week) was included as an independent variable in a multiple linear regression analysis, along with the following potential confounders: age, Quetelet index, alcohol consumption, cigarette smoking, heart rate, and level of education. In this analysis the sports-BP relationship was considerably attenuated or entirely disappeared. It remained statistically significant only in the age class 50-59 (p less than 0.01 for systolic BP an p less than 0.05 for diastolic BP). Our results support those of others showing a modest beneficial effect of leisure time physical exercise on BP.(ABSTRACT TRUNCATED AT 250 WORDS)

[Contribution of digital venous angiography to the evaluation of arterial hypertension. Cost evaluation]. / Apport de l'angiographie numérisée par voie veineuse dans le bilan de l'hypertension artérielle. Evaluation du coût.

Concerning 100 intravenous digital subtraction angiographies (IV DSA) performed for the study of arterial hypertension, the results are discussed according to two different achievements: diagnostic and economic. One hundred patients have been examined after the intravenous (IV) injection of contrast material, seventy times in peripheral and thirty times in central venous system. Out of 94 examinations that could be interpreted, 10 revealed stenosis of renal arteries higher than 50 per cent, one revealed fibromuscular dysplasia. IV DSA generally permits the correct study of renal arteries and compared to conventional angiography it gives only a small number of false negative results. However, the reliable study of intrarenal vascularisation can be obtained only by renal arteriography. The renal arteriography remains therefore necessary: when renal IV DSA gives insufficient data; to estimate the degree of stenosis in fibro-muscular dysplasia; to evaluate intrarenal vascularisation before renovascular surgery or angioplasty. To estimate the economic validity of renal IV DSA for the study of arterial hypertension, we have investigated: the actual cost of the examination for a department of radiology, compared with the cost of conventional examination; on the other hand, the influence of this examination on the duration of hospitalisation for evaluation of arterial hypertension. According to our investigation, this examination allows the average reduction of expenses for 180 F per patient with arterial hypertension, and shortens the time of hospitalisation for about one day. Owing to this diagnostic and economic contribution, renal IV DSA is becoming the first examination to be done for the evaluation of renovascular hypertension.