Biomedical subjects

L Tiret

Publications and source records attributed to L Tiret.

At least 91 records · Page 5Linked to original sources

PubMed1994

Expression of a paternal history of premature myocardial infarction on fibrinogen, factor VIIC and PAI-1 in European offspring--the EARS study. European Atherosclerosis Research Study Group.

To assess the role of genetic and environmental factors in the predisposition to atherosclerosis, 682 students whose father had suffered a myocardial infarction before the age of 55 ("cases") and 1312 controls matched for age and sex, were recruited from 14 Universities in Europe. Fibrinogen, factor VIIc and PAI-1 were compared between cases and controls across European regions. Fibrinogen and factor VIIc were positively correlated with BMI, smoking and contraception. PAI-1 was positively and independently correlated with BMI and waist-to-hip ratio, and negatively with contraception. Factor VIIc and PAI-1 were correlated with cholesterol and triglycerides, and fibrinogen was weakly correlated with LDL-cholesterol. After adjustment for covariates and lipids, fibrinogen level was significantly higher in male cases than in controls (2.38 vs 2.29, p < 0.01). No such difference was found in females (2.59 vs 2.57 - NS). There was no significant case/control difference for factor VIIc and PAI-1. These results support the hypothesis that fibrinogen is a transmissible risk factor of coronary artery disease in males. No such evidence was provided for factor VIIc and PAI-1.

Adolescent↗

PubMed1993

Reliability of reported family history of myocardial infarction.

OBJECTIVE: To assess the reliability of reported family histories of myocardial infarction. DESIGN: A case-control study in which reported histories of first degree relatives were validated from death certificates, general practitioners' records, and hospital notes. SETTING: Participants enrolled in the Belfast centre of the World Health Organisation's study monitoring trends and determinants in cardiovascular disease (MONICA). SUBJECTS: 200 men who survived myocardial infarction and 200 age matched controls drawn randomly from the population. MAIN OUTCOME MEASURES: The sensitivity, specificity, positive predictive value, and proportion of overall agreement with validated records of reported family histories of myocardial infarction in first degree relatives; odds ratios for myocardial infarction, given at least one reported relative or at least one verified relative being affected. RESULTS: 349 of the 400 probands provided detailed family histories, reporting on 2812 first degree relatives. The overall sensitivity, specificity, and positive predictive value of reported histories were 67.3%, 96.5%, and 70.5% for cases and 68.5%, 97.7%, and 73.8% for controls. The kappa coefficients were modest: 0.65 for cases and 0.68 for controls. The odds ratios for myocardial infarction, given at least one affected relative, were not substantially inflated by recall bias. Some recall bias was evident for the probands' reports of their siblings' histories of myocardial infarction, the odds ratio for a reported history being 1.67 (95% confidence interval 1.09 to 2.57) and for the validated history 1.54 (1.01 to 2.37). CONCLUSIONS: Although the relative risk of disease is correctly estimated, the predictive accuracy of a casual family history of myocardial infarction may limit the effectiveness of targeted screening programmes. They may, however, complement other strategies based on genetic testing.

Case-Control Studies↗

PubMed1993

Deletion polymorphism in angiotensin-converting enzyme gene associated with parental history of myocardial infarction.

In a European study an insertion (I)/deletion (D) polymorphism in the angiotensin converting enzyme (ACE) gene has been shown to be associated with the risk of myocardial infarction (MI). In the same study, we investigated the association of the polymorphism with a parental history of fatal MI. There was an excess of both DD (odds ratio 2.6, p = 0.02) and ID (odds ratio = 1.9, p = 0.08) genotypes among those having a parental history of MI, confirming that genetic variation in the ACE locus could be involved in the risk of MI.

Adult↗

PubMed1993

Effect of ignoring genotype-environment interaction on segregation analysis of quantitative traits.

Thirty replicates of 200 nuclear families (6 members each) were generated under three GxE interaction models. Segregation analyses of these data were performed using a regressive model taking into account an interaction effect or not. Results showed that ignoring the GxE interaction markedly decreased the power for accepting a major gene and led to serious bias in parameter estimates.

Adult↗

PubMed1993

Polymorphisms of the apolipoprotein B and E genes and their relationship to plasma lipid variables in healthy Chinese men.

In this study we have analysed the apolipoprotein (Apo) E polymorphism and polymorphisms of the ApoB gene, including the ApoB/XbaI and ApoB/4311 diallelic polymorphisms and a hypervariable region (HVR) situated in the 3' region of the gene (ApoB/3'HVR), in a sample of healthy male subjects from Taiyuan (northern People's Republic of China). In comparison to Caucasian populations, in the Chinese sample, the XbaI2 allele (presence of cutting site; frequency 6.1%; and 95% confidence interval, 3.3-8.9) and the long HVR alleles (9.4%; 6.0-12.8) were rare, whereas the ApoB/4311 (Ser) allele (70.8%; 65.4-76.2) and the 34-repeat allele of the HVR (HVR34; 62.4%; 56.8-68.0) were frequent. In subjects having none, one, or two HVR34 alleles, the mean levels of plasma triglycerides were 2.32 +/- 1.44 (SD), 1.45 +/- 0.74, and 1.75 +/- 1.07 g/l, respectively (P < 0.007). Similar trends were observed for very low density lipoprotein (VLDL) cholesterol, LpE:B, and LpCIII:B. The frequencies of the ApoE alleles were similar to those reported in other populations of Asian origin; E2 (7.4%; 4.2-10.6), E3 (84.4%; 80.2-88.6), and E4 (8.2%; 5.0-11.4). Individuals carrying the E2 allele had a lower mean level of ApoB than E33 individuals: 0.87 +/- 0.16 and 1.00 +/- 0.22 g/l, respectively (P < 0.007). Individuals carrying the E4 allele had higher levels of ApoE than E33 individuals: 0.140 +/- 0.084 and 0.094 +/- 0.052 g/l, respectively (P < 0.004); similar trends were observed for VLDL cholesterol, triglycerides, LpE:B, and LpCIII:B. The ApoB/HVR34 and ApoE/E4 polymorphisms accounted for 10% to 15% of the variability of the plasma levels of VLDL cholesterol, ApoE, triglycerides, LpE:B, and LpCIII:B. Several lipid variables appeared to be favourably affected by specific forms of ApoB and ApoE that are particularly frequent in this Chinese population.

Adult↗

PubMed1993

Inference of the strength of genotype-disease association from studies comparing offspring with and without parental history of disease.

The association between genetic polymorphisms and a multifactorial disease is generally investigated by case-control studies. However, inference about the genotype-disease association can also be drawn from studies comparing offspring having a parental history of disease with offspring having no parental history. In such studies, differences in genotype frequencies between the two groups of offspring will reflect a different transmission of alleles from affected and unaffected parents. We showed that in offspring studies, the odds ratios (ORs) associated with heterozygous and homozygous genotypes are related by the formula: OR(het) = (OR(hom) + 1)/2. These ORs depend only on the allele frequencies in affected and unaffected parents, and not on the pattern of genotype-disease association. Under simple patterns of association, it is possible to infer from the ORs observed among offspring, the expected ORs for the disease. The decrease of power of offspring studies by comparison with classical case-control studies is evaluated, and an application is given on the association between the apoE polymorphism and coronary heart disease.

Adult↗

PubMed1993

Altering the spatial determinations in the mouse embryos by manipulating the Hox genes.

Developmental genetics in Drosophila led to the isolation of the homeotic genes which are involved in the cellular positional information. In vertebrates, homologous genes have been characterized and play similar roles in the spatial determination. However, the subtle mechanisms by which positional identity is specified by the Hox genes co-expression are little known. The Hoxc-8 null mutation can induce homeosis at the anterior margin of Hoxc-8 expression, where the mosaicism observed suggests that, at least in the segmented paraxial mesoderm, the number of cells expressing a Hox gene is a determinant parameter. A combinatorial model is also suggested by several genetic experiments where the level of Hox genes expression is modified. Expression of some related Hox genes in Hoxc-8 homozygous mutants is not altered, suggesting the absence of genetic interregulations between these genes.

Animals↗

PubMed1992

Inhibited gastrulation in mouse embryos overexpressing the leukemia inhibitory factor.

Leukemia inhibitory factor (LIF) is a cytokine active in vitro on different target cells. It is detected in vivo during mouse gestation in both extraembryonic membranes and maternal tissues. Two isoforms have been described maintaining embryonic stem cells in culture in a pluripotent state. However, overexpression of their cDNAs in chimeric mouse embryos observed between 6.5 and 9.5 days postcoitus gave strikingly different phenotypes. Embryos overexpressing the diffusible form of LIF cDNA looked essentially normal. Chimerae expressing LIF associated with the extracellular matrix cDNA showed an abnormal proliferation of tissues and the absence of differentiated mesoderm. They have not undertaken the normal pathway of gastrulation.

Animals↗

PubMed1992

Segregation analysis of height-adjusted weight with generation- and age-dependent effects: the Nancy Family Study.

A segregation analysis using a regressive model with generation- and age-dependent effects was applied to familial data of height-adjusted weight to investigate the major gene hypothesis. The sample included 629 nuclear families with 2,534 members volunteering for a free health check-up in the Preventive Medicine Center of Vandoeuvre-lès-Nancy, France. The familial correlations were 0.094 +/- 0.040 between spouses, 0.198 +/- 0.023 between parent and offspring, and 0.327 +/- 0.034 between siblings. The variability of the trait was higher in parents than in offspring. The most parsimonious genetic model indicated a codominant major effect increasing with age in childhood, then stabilizing in adulthood. The same data were analyzed using the classical mixed model, assuming equality of variances between parents and offspring, no resemblance between spouses, similar parent-offspring and sib-sib correlations, and identical effects in parents and offspring. This analysis indicated a recessive solution. In both analyses, mendelian transmission was rejected. However, the mixture of two distributions in the recessive model, instead of three in the codominant one, was less constraining with respect to the test of transmission probabilities, and the rejection of mendelian transmission was due to a single family in the recessive case, instead of several families in the codominant one. This could possibly explain why previous studies, all using the mixed model, found evidence for a recessive major gene. Although the major gene hypothesis cannot be definitely ruled out from our results, the mechanism appears more complex than the effect of one single gene.

Adolescent↗

PubMed1992

Evidence, from combined segregation and linkage analysis, that a variant of the angiotensin I-converting enzyme (ACE) gene controls plasma ACE levels.

The hypothesis of a genetic control of plasma angiotensin I-converting enzyme (ACE) level has been suggested both by segregation analysis and by the identification of an insertion/deletion (I/D) polymorphism of the ACE gene, a polymorphism contributing much to the variability of ACE level. To elucidate whether the I/D polymorphism was directly involved in the genetic regulation, plasma ACE activity and genotype for the I/D polymorphism were both measured in a sample of 98 healthy nuclear families. The pattern of familial correlations of ACE level was compatible with a zero correlation between spouses and equal parent-offspring and sib-sib correlations (.24 +/- .04). A segregation analysis indicated that this familial resemblance could be entirely explained by the transmission of a codominant major gene. The I/D polymorphism was associated with marked differences of ACE levels, although these differences were less pronounced than those observed in the segregation analysis. After adjustment for the polymorphism effects, the residual heritability (.280 +/- .096) was significant. Finally, a combined segregation and linkage analysis provided evidence that the major-gene effect was due to a variant of the ACE gene, in strong linkage disequilibrium with the I/D polymorphism. The marker allele I appeared always associated with the major-gene allele s characterized by lower ACE levels. The frequency of allele I was .431 +/- .025, and that of major allele s was .557 +/- .041. The major gene had codominant effects equal to 1.3 residual SDs and accounted for 44% of the total variability of ACE level, as compared with 28% for the I/D polymorphism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1992

Posttraumatic disablement: a prospective study of impairment, disability, and handicap.

This study was designed to evaluate both the frequency and the course of impairments, disabilities, and handicaps resulting from trauma. It was conducted in Aquitaine, France, on a sample of 1005 trauma patients (mean ISS, 10.5 +/- 0.3) in which severe trauma (ISS > 25) was rather overrepresented (169 of 1005). A prospective follow-up of disablement according to the WHO classification was based on medical examinations performed 6 and 12 months after the trauma. Of 664 survivors reviewed at 6 months, the findings were cross tabulated with Injury Severity Score (ISS) and age. There was a good relationship between ISS and the mean length of stay in the hospital (r = 0.46; p < 0.001), the duration of rehabilitation, and the time away from work or school. Out of this sample of 1005 patients with rather major injuries, 73% of the survivors suffered from at least one impairment, with a consistently lower frequency in children whatever the severity. At least one disability was encountered in 52.3% of these patients depending on both ISS and age. Handicap was noted in at least 26% of the cases. Between the sixth month and the end of the first year, the minimal handicap regression was 35.8%, whereas the minimal regression of the disability rate was 19.5%. The best improvement was observed essentially in the low ISS categories. Whereas for minor trauma the course of disablement seems to be fixed 1 year after the injury, such is not the case for severe trauma.

Absenteeism↗

PubMed1991

Testing for association between disease and linked marker loci: a log-linear-model analysis.

One approach frequently used for identifying genetic factors involved in the process of a complex disease is the comparison of patients and controls for a number of genetic markers near a candidate gene. The analysis of such association studies raises some specific problems because of the fact that genotypic and not gametic data are generally available. We present a log-linear-model analysis providing a valid method for analyzing such studies. When studying the association of disease with one marker locus, the log-linear model allows one to test for the difference between allelic frequencies among affected and unaffected individuals, Hardy-Weinberg (H-W) equilibrium in both groups, and interaction between the association of alleles at the marker locus and disease. This interaction provides information about the dominance of the disease susceptibility locus, with dominance defined using the epidemiological notion of odds ratio. The degree of dominance measured at the marker locus depends on the strength of linkage disequilibrium between the marker locus and the disease locus. When studying the association of disease with several linked markers, the model becomes rapidly complex and uninterpretable unless it is assumed that affected and unaffected populations are in H-W equilibrium at each locus. This hypothesis must be tested before going ahead in the analysis. If it is not rejected, the log-linear model offers a stepwise method of identification of the parameters causing the difference between populations. This model can be extended to any number of loci, alleles, or populations.

Alleles↗

PubMed1990

Familial resemblance of plasma apolipoprotein B: the Nancy study.

The familial resemblance of plasma apolipoprotein B (apo B) was investigated in a sample of 102 families including 419 members who volunteered for a free health checkup in the Preventive Center of Vandoeuvre-lès-Nancy, France. The mean levels (+/- SD) of apo B were 141.0 (+/- 32.6), 121.8 (+/- 27.7), and 98.6 (+/- 22.6) mg/dl in fathers, mothers, and offspring, respectively. The familial correlations were 0.04, 0.13, 0.21 (P less than .01), and 0.47 (P less than .001) between spouses, father-offspring, mother-offspring, and siblings, respectively, after adjustment on age, body mass index, and sex. A genetic analysis was performed using the approach proposed by Bonney, which indicated that a recessive and a dominant major-locus model appeared nearly equally supported by the data. Under the recessive model, the frequency q of the most common allele was estimated as 0.825, with a mean difference of 60.4 mg/dl between high and low homozygotes. Under the dominant model, q was estimated as 0.875, with a mean increase of 34.2 mg/dl in heterozygotes and high homozygotes. However, the hypothesis of Mendelian transmission and the environmental hypothesis could not be formally tested because of great numeric difficulties encountered in the estimation of the three transmission probabilities. Given these analytical restrictions, we cannot conclude in favor of a major locus influencing apo B level in our population, even though the evidence is suggestive. The genetic heterogeneity underlying the familial aggregation of apo B level, suggested by several recent publications, might explain the difficulty in discerning a single major locus in a population sample of small nuclear families, not ascertained through patients enriching the sample in high values of apo B. These findings call into question the relevance of the approach through "healthy" populations in the search for major loci influencing biological traits.

Adult↗

PubMed1990

The epidemiology of head trauma in Aquitaine (France), 1986: a community-based study of hospital admissions and deaths.

This paper reports the findings of a study of head trauma conducted over a one-year period within a defined region with a population of 2.7 million (Aquitaine, France). It includes cases resulting in death prior to hospitalization or requiring hospitalization. During the one-year period, 391 deaths and 8549 hospital admissions due to head trauma occurred, yielding an annual estimate of 8940 head-injured people. The immediate case-fatality rate was 4.4%. Among non-fatal cases, 80% were mild, 11% moderate and 9% severe. The overall annual incidence was 281/100,000 in both sexes (384 and 185/100,000 in males and females respectively). The annual death rate was 22/100,000 (33 and 12, respectively). Patterns of incidence by age and sex were in general agreement with earlier studies. The main causes of head trauma were traffic accidents (60%) and falls (33%). One-third of hospitalized patients had no injury other than the head trauma. The most frequently associated injuries were those involving extremities, whereas the most severe were those involving the abdomen. The Injury Severity Score (ISS) ranged from 4 to 66, with a mean of 9 and a median of 5. At the eighth day following injury, 25% of hospital-treated patients were still hospitalized and 2% had died. The outcome correlated well with the ISS.

Accidental Falls↗

PubMed1989

Incidence, causes and severity of injuries in Aquitaine, France: a community-based study of hospital admissions and deaths.

This paper reports the results of a study of injuries conducted during a one-year period within a defined geographic population of 2.7 million persons (Aquitaine, France). Cases were defined as unintentional or intentional injuries, either resulting in immediate death before reaching hospital or requiring hospital admission. During the one-year period, 1,181 deaths were registered and 8,190 hospital admissions occurred during the sample periods. The three leading causes of injury were falls (40 per cent), traffic accidents (27 per cent), and poisonings (15 per cent). The overall incidence of injuries was 136 per 10,000 person years. Incidence by sex and age was assessed for the main external causes. The ratios of nonfatal to fatal cases were calculated by sex and age and by external cause. The origin of the injury was suicide in 14 per cent of cases and assault or homicide in 3 per cent. The severity of injuries, assessed using an automatic computation of the Injury Severity Score (ISS), ranged from 1 to 66 with a mean of 6.9. Substantial variations of ISS were observed according to external cause. At the 8th day following admission, 31 per cent of hospital-treated patients were still hospitalized and 0.8 per cent had died in hospital. The outcome correlated well with the ISS.

Accidental Falls↗

PubMed1989

[Injuries and poisoning caused by various types of activities. Epidemiologic survey on death and hospitalization in Aquitaine].

From the data of a survey conducted in 1986 within the French area of Aquitaine and based on a representative sample of injuries having led to immediate death or hospitalization, different types of injuries were compared. Domestic and recreational accidents constituted the leading cause (41%) of injuries, followed by traffic accidents (28%) and suicides (13%). The overall ratio of immediate deaths to hospitalizations was 1 to 30 (1 to 10 for suicides, 1 to 20 for traffic accidents and 1 to 80 for domestic accidents). The overall annual incidence was 131 per 10,000 (respectively 20, 34 and 53 for suicides, traffic accidents and domestic accidents). The incidence by sex, age and type of accident was assessed. Among hospitalizations, about 3/4 of domestic and school accidents were falls; 45% of work accidents were cutting-piercing or being struck by an object, and 40% were falls; 90% of attempted suicides were poisonings. Using the Injury Severity Score (ISS), severity of injuries was the highest in traffic accidents. Traffic accidents also led to the highest hospital mortality within eight days (1.6%).

Accidents↗

PubMed1988

Prediction of outcome of anaesthesia in patients over 40 years: a multifactorial risk index.

The prediction of outcome of anaesthesia in patients over 40 years of age was assessed using a multifactorial index based on current preoperative factors recorded prospectively. The study was conducted using a representative sample of anaesthetizations (except for cardiac surgery) including 517 cases with major complication (occurring during or within 24 hours of anaesthesia) and a one in fifty random sample comprising 1538 cases without complication. A split sample approach was adopted and a logistic regression model was applied to two subsets of similar size. Four preoperative factors were significantly associated with the occurrence of complications: ASA physical status, age, surgical procedure (major/minor) and type (elective/emergency). Goodness-of-fit of the model was assessed using another sample of 332 cases with complication and a different subset of 987 cases without complication. The model fitted the data well (p = 0.15).

Age Factors↗

PubMed1988

The implications of a national study of risk of anaesthesia.

In order to set up measures to improve safety in anesthesia, the French Ministry of Health charged the Institut National de la Santé et de la Recherche Médicale (I.N.S.E.R.M.) with conducting an epidemiological survey of complications associated with anaesthesia. A prospective survey was carried out from 1978 to 1982 in a representative sample of 198,103 anaesthesias performed in 460 public and private institutions randomly selected throughout the country. There were 268 major complications associated with anaesthesia occurring during or within 24 hours after anaesthesia (incidence 1.35 per 1000), among these 67 were followed by death and 16 by coma. The incidence of deaths and comas totally attributable to anaesthesia was one per 7924. Half of the deaths and comas totally attributable to anaesthesia were from post-anaesthetic respiratory depression which could be directly linked to a dramatic lack of recovery rooms. The extension of the study to all institutions revealed that 25% of teaching hospitals, 43% of non-teaching hospitals and 20% of private clinics did not have a recovery room available. A total number of 12,000 recovery beds was estimated to be necessary in France; 40% being currently available leaving 60% to be created.

Anesthesia↗