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Biomedical subjects

A Chevalier

Publications and source records attributed to A Chevalier.

At least 19 recordsLinked to original sources
PubMed2006

The Wip1 phosphatase (PPM1D) antagonizes activation of the Chk2 tumour suppressor kinase.

We previously demonstrated that type 2C protein phosphatases (PP2C) Ptc2 and Ptc3 are required for DNA checkpoint inactivation after DNA double-strand break repair or adaptation in Saccharomyces cerevisiae. Here, we show the conservation of this pathway in mammalian cells. In response to DNA damage, ataxia telangiectasia mutated (ATM) phosphorylates the Chk2 tumour suppressor kinase at threonine 68 (Thr68), allowing Chk2 kinase dimerization and activation by autophosphorylations in the T-loop. The oncogenic protein Wip1, a PP2C phosphatase, binds Chk2 and dephosphorylates phospho-Thr68. Consequently, Wip1 opposes Chk2 activation by ATM after ionizing irradiation of cells. In HCT15 colorectal cancer cells corrected for functional Chk2 activity, Wip1 overexpression suppressed the contribution of Chk2 to the G2/M DNA damage checkpoint. These results indicate that Wip1 is one of the phosphatases regulating the activity of Chk2 in response to DNA damage.

Ataxia Telangiectasia Mutated Proteins↗
PubMed2006

APRAND programme: an intervention to prevent relapses of anxiety and depressive disorders. First results of a medical health promotion intervention in a population of employees.

OBJECTIVE: The study sought to determine whether an organized health promotion intervention during medical consultations improves the outcome for patients who meet the ICD10 criteria for anxiety or depressive disorders. METHODS: In 2001, physicians used the MINI to screen 9743 employees on sick leave and consulting physicians in 21 medical centres of a large company. A health promotion intervention was implemented in eight "active" centres. It took place immediately after diagnosis and consisted of explaining the disorders, delivering the test results and leaflets based on WHO recommendations, and advising patients to consult their personal physician, psychiatrist or occupational physician, if necessary. Its effectiveness, evaluated by symptom severity and outcome over 1 year, was assessed by comparing the eight active centres to 13 control centres (without the intervention). RESULTS: Disorders were detected among 10.6% of the subjects, 29.4% of whom had no previous diagnosis of anxiety or depressive disorder. The intervention was associated with a positive effect on the 6-week and 6-month HAD scores. Total absence of disorders at 1 year was associated with age, sex, and intervention, among all identified cases (OR=1.53), among those with at least one anxiety disorder (OR=1.45), and among those with at least one depressive disorder (OR=1.40). CONCLUSION: Combining detection with organized provision of information including printed material improves patients' outcome and physicians' diagnostic abilities.

Adult↗
PubMed2005

[Initial or interval debulking surgery for advanced stage ovarian cancer: state-of-the-art. How to select patients?].

The management of advanced stage ovarian cancer has been deeply modified over the last few years. In patients with massive peritoneal spread, the use of neoadjuvant chemotherapy, followed by interval surgery, reduces the morbidity of radical surgery with an improvement of the quality of life. Nevertheless, results of ongoing randomized studies should be waited before stating about the results on survival of such management compared to initial debulking surgery. Waiting such results, the standard treatment of advanced stage ovarian cancer in 2005 remains initial surgery, performed in order to obtain ideally a total resection of all macroscopic diseases, and followed by adjuvant chemotherapy. However, in patients with massive spread, interval debulking surgery is becoming an interesting option, and will perhaps become a standard management. But criteria to select patients between initial and interval debulking surgery should be clearly defined. Those different points will be studied in this paper.

Chemotherapy, Adjuvant↗
PubMed2005

A case of stunning of lung and bone metastases of papillary thyroid cancer after a therapeutic dose (3.7 GBq) of 131I and review of the literature: implications for sequential treatments.

Thyroid stunning is usually defined as the inhibition or suppression of iodide trapping by remnant thyroid tissue or by functioning metastases following a diagnostic dose of 131I. The risk of stunning increases progressively with larger doses. Because the threshold above which this effect occurs in thyroid remnants seems to be between 37 MBq and 111 MBq of 131I, therapeutic 131I doses of 3.7 GBq may cause stunning. We describe stunning of papillary thyroid cancer lung and bone metastases after a therapeutic dose of 131I (3.7 GBq). A T1 bone metastasis and bilateral lung metastases were diagnosed by post-therapeutic dose whole-body scan. Nuclear MRI detected another lesion at T4, whose 131I fixation was not obvious. An additional 0.7 GBq were given after recombinant TSH, 37 days after the therapeutic dose; 24 h later, uptake by the lung and T1 metastases had disappeared, but trapping was again seen 6 months later on the post-therapeutic scan. This re-appearance is evidence in favour of the transitory and reversible character of stunning, and confirms its correspondence to the decreased ability of viable thyroid cells to trap iodine and not to their destruction. A better understanding of stunning would make it possible, in the event of rapidly progressing disease and in conjunction with recombinant thyroid stimulating hormone (TSH), to give several therapeutic doses of 131I in close succession without each dose hampering the effectiveness of the subsequent one.

Adolescent↗
PubMed2004

Anxiety or depressive disorders and risk of ischaemic heart disease among French power company employees.

BACKGROUND: The aim of this study was to determine whether depression and anxiety are predictive factors for ischaemic heart disease among adults <60 years. Method A case-control study among active employees of the French nationwide power company (Electricité de France-Gaz de France) analysed men aged 31-55 years who presented an initial clinical form of ischaemic heart disease from 1993 through 1997, collected from the company registry. These 660 men were each matched by age to 10 controls per case. Adjusted odds ratios (OR) were calculated by logistic regression. RESULTS: There was a significant association between ischaemic heart disease and sick-leave for any medical reason in the 3 years before its onset (OR = 1.79; 95% CI: 1.50, 2.14). This association was strengthened when only absences for depression and anxiety were considered (OR = 3.10; 95% CI: 2.29, 4.19) and remained important and significant when adjusted for socioeconomic status: OR = 2.66 (95% CI: 1.95, 3.63). A previous sick-leave for depression or anxiety in the 10 years before the heart disease strengthened the association (OR = 3.61; 95% CI: 2.39, 4.45), which was further reinforced by an elevated number (> or =4) of such sick-leaves (OR = 5.11; 95 % CI: 3.11, 8.40). CONCLUSION: Depressive and anxiety disorders that lead to absenteeism seem to be associated with an increased risk of ischaemic heart disease in the 3 years thereafter, especially when depression and anxiety were severe and chronic; this association is independent of socioeconomic status.

Absenteeism↗
PubMed2003

Effects of dipeptide administration on hypoglycaemic counterregulation in type 1 diabetes.

OBJECTIVES: To investigate if a dipeptide made of glutamine and alanine is able to contribute to the recovery from insulin-induced hypoglycaemia in type 1 diabetes. RESEARCH DESIGN AND METHODS: Fifteen adult type 1 patients were randomly assigned to study group (n=7): intravenous infusion of 20 g Dipeptiven in normal saline (i.e., 8 g alanine and 13 g glutamine), or control group (n=8): same infusion, normal saline only. A 150 min gradual hypoglycaemic hyperinsulinemic clamp was administered after 2 h of infusion. Counterregularory hormones, symptoms, and cognitive function (4 choice reaction test) were regularly measured during the study. RESULTS: Blood glucose and glucose infusion rates were similar in the 2 groups. Circulating levels of alanine and glutamine peaked at 90 min and remained elevated throughout the test. This was associated with significant differences in: glucagonemia 107 +/- 20 vs 58 +/- 8 pg/ml, and neuroglycopenic symptoms scores: 7 +/- 3 vs 18 +/- 13, at t 150 min, in study and control group, p<0.05. Dysautonomic symptoms, cognitive tests as well as epinephrine, norepinephrine, cortisol and growth hormone were similar between groups. CONCLUSION: Intravenous infusion of a dipeptide made of alanine and glutamine is capable to reactivate glucagon secretion during insulin-induced hypoglycaemia and to reduce hypoglycaemic symptoms.

Adult↗
PubMed2003

[Value of MRI in symptomatic patients treated with tamoxifen].

PURPOSE: To assess the MR imaging (MRI) findings in symptomatic tamoxifen treated-women with abnormal transvaginal sonography. PATIENTS AND METHODS: From january 1997 to june 2000, 32 consecutive symptomatic tamoxifen treated-women with abnormal transvaginal sonography were prospectively studied by MRI. T1-weighted, T2-weighted, post-contrast T1-weighted and dynamic gradient-echo T1-weighted sequences were used. All patients underwent uterine sampling within one month of MRI. RESULTS: Endometrial thickness at sonography ranged from 5 to 48 mm (mean thickness 19 mm), and on T2-weighted imaging ranged from 3 to 50 mm (mean=25 mm). Three MRI patterns were found. Pattern 1 (13 patients) was defined as homogeneous high signal intensity of the endometrium on T2W images, and signal void in the lumen on gadolinium-enhanced images. Pattern 2 (8 patients) was defined as heterogeneous endometrial signal on T2W images, and latticelike enhancement traversing the endometrial canal on gadolinium-enhanced images. Pattern 3 (11 patients) was defined as heterogeneous signal on T2W images with masses or nodules which were better seen on dynamic gadolinium-enhanced images. In pattern 1 we found 13 atrophic endometrium, in addition there were 4 polypoid glandulo-cystic proliferation (PGCP), and 1 adenomyosis. In pattern 2 we found 3 PGCP, 4 atrophy and 1 polyp without hyperplasia. The 2 carcinomas and the polyps with hyperplasia were found in pattern 3 (11 patients). CONCLUSION: In our experience MRI allows differentiation of lesions which may require surgery from other lesions in which noninvasive follow-up is possible.

Aged↗
PubMed2003

[Mortality among active workers at EDG-GDF: social and occupational disparities and evolution].

BACKGROUND: Two studies, conducted in the eighties and the nineties, reported that mortality was lower in the French national electric and gas company (EDF-GDF) the utility workers than in the general French population. The purpose of our study was to compare the mortality of these 140,000 utility workers to that of the French population of the same age for the period from 1997 to 2001. Secondly we aimed to assess the disparities of mortality among the workforce according to demographic and socioprofessional criteria. Finally, we analyzed the evolution of this mortality over the last twenty years. METHODS: We undertook a cross-sectional study using the indirect standardization method. RESULTS: Risk of death was lower in the utility workers than in the French population (SMR=54% for men, and 58% for women). These differences had increased over the last twenty years for each main cause of death (cancers, cardio-vascular diseases and accidents). The reported excess of brain cancer death risk raises etiologic questions. Moreover, we noticed important social disparities in the workforce, increasing with time. CONCLUSION: The well-known "healthy worker effect" seems to be particularly important in the EDF-GDF company. The workers have a high level of living conditions and good working conditions, although internal social disparities persist. Further studies in other large corporations are greatly needed for comparisons.

Accidents↗
PubMed2002

Differential metabolization of the impact of life events on subjects hospitalized for depressive and anxiety disorders: case-control study.

BACKGROUND: The study of the relationship between life events and mental illness has progressed considerably over the last 30 years. Practically all mental disorders have been explored using a variety of methods of variable value. The results are in favor of the existence of a temporal link between life events and illness. The part played by life events is the most pronounced in triggering depressive disorders and attempted suicide. Many aspects of this relationship have been explored, but the ability to metabolize the event impact over time has never been studied. This paper reports the results of a longitudinal study. Its objective is to make a comparative study of the ability to metabolize event impacts in depressive in-patients and controls. METHODS: The investigation was designed as a longitudinal, clinical, case-control study constructed on in-patients with depressive and anxiety disorders (n=25) and healthy controls from the community (n=28). The absence or presence of mental pathology was assessed using the SCAN, events and event-impacts were reported by subjects from a list of events constructed from the LEDS framework. RESULTS: The results show that the ability to metabolize the event-impact is positively linked to the mental health status of subjects, and that the first self-assessment of the event-impact has a good predictive capacity on the progression of this score a few months later and then 15-18 months later both in in-patients and in controls.

Adult↗
PubMed2002

eNOS4 polymorphism of the endothelial nitric oxide synthase predicts risk for severe diabetic retinopathy.

BACKGROUND: Genetic factors may be involved in the development, and particularly in the severity, of diabetic retinopathy (DR), in addition to chronic hyperglycaemia. Increased nitric oxide generation has been suggested to play a significant role in the pathogenesis of DR. AIMS AND METHODS: To examine whether the eNOS4 is involved in the risk of severe DR, 200 unrelated Caucasian Type 1 diabetic patients of long duration were randomly selected (M/F 103/97, age 44.4 +/- 12.4 years, diabetes duration 27.7 +/- 10.0 years, body mass index 24.3 +/- 3.4 kg/m2, HbA1c 8.6 +/- 1.3%). The eNOS4 polymorphism was analysed by polymerase chain reaction, and DR by retinal angiography and classified as presence (n = 101) or absence (n = 99) of severe (proliferative or pre-proliferative) DR. RESULTS: The genotype distribution of eNOS4b/b (wild-type), eNOS4b/a (heterozygous) and eNOS4a/a (homozygous) was 72%, 24.5% and 3.5%, respectively. Frequency of eNOS4a/a was significantly lower in patients with severe DR (n = 0) when compared with controls (n = 7, odds ratio (OR) = 0 (95% confidence interval (CI) = 0.5-0.74), P = 0.02). eNOS4b/b was more frequent in patients with severe DR (n = 80) when compared with controls (n = 64, OR = 2.1 (95% CI = 1.1-4.12), P = 0.032). Frequency of eNOS4b/a was not different between the study (n = 21) and control groups (n = 28, ns). The allelic frequencies between the study and control groups were different (4b: n = 181 vs. n = 156, respectively, OR = 2.3 (95% CI = 1.27-4.25), P = 0.005; 4a: n = 21 vs. n = 42, respectively, OR = 0.4 (95% CI = 0.24-0.79), P = 0.005). CONCLUSIONS: We demonstrate in Caucasians with Type 1 diabetes that (i) eNOS4a/a is associated with absent or non-severe DR, and (ii) eNOS4b/b is associated with severe DR.

Adult↗
PubMed2002

Epidemiological surveillance at Electricité de France-Gaz de France: health assessment of nuclear power plant employees between 1993 and 1998.

Because the 17,500 employees working in nuclear power plants at Electricité de France, the national power company, may be exposed to a wide variety of industrial hazards, the health insurance department of the company has set up an epidemiological surveillance programme for them. This report describes its first stage, an analysis of their health problems. This descriptive, cross-sectional and exhaustive study examined sick-leave, mortality and cancer incidence to assess the health of the employees working from 1993 through 1998. The analysis compared the employees in nuclear power plants, considered 'exposed', with the rest of the personnel of Electricité de France-Gaz de France, the 'non-exposed' (125,000 persons). Relative risks for these variables were estimated, after stratification for age, sex and work grade. Globally, the employees in the nuclear sector appeared to have fewer health problems than the other company employees. This was true regardless of age and especially for men, operating employees and supervisory employees. Nonetheless, three points must be noted: non-work accidents generated a non-significant excess of absenteeism and mortality among these employees, especially among management and supervisory personnel; suicides affected supervisors in particular; and an excess of primary malignant brain tumours affected both mortality [relative risk (RR) = 1.96, n.s.] and incidence, especially among operating employees (RR = 2.87, 95% confidence interval = 1.00-8.43). No excess of malignant blood disease was observed. This study, performed for surveillance purposes, points to brain tumours as a problem that raises important aetiological questions. Research is now necessary to provide answers. Surveillance of nuclear plant employees at Electricité de France should be continued and expanded to include the study of specific occupational exposures.

Adult↗
PubMed2002

[Domestic, leisure activity and sports-related accidents in an active population: perspectives for prevention by health education].

Resulting from the findings of epidemiological surveys on non-work-related accidents conducted in 1996 and 1997 among employees covered by a special health insurance programme for gas and electric company workers, this article identifies avoidable and recurrent accidents that may be targeted by health education interventions. It also emphasizes the importance of considering the needs expressed by the population at large when developing the themes for information campaigns. Finally, it proposes a sequel to the "survey-action plan" released in 1996. The proposed follow-up takes into account the occupational setting and its professionally-related barriers, and includes delivering prevention messages, conducting in-house experimental health promotion activities (and evaluating them), and disseminating intermediary external campaigns aimed at impeding avoidable accidents among adults. The preventable accidents identified in this study are not specific to the employed population group studied here; they may also be targeted by more general health promotion programmes and interventions.

Accident Prevention↗
PubMed2001

Socioeconomic, demographic, occupational, and health factors associated with participation in a long-term epidemiologic survey: a prospective study of the French GAZEL cohort and its target population.

The purpose of this paper is to examine personal and health factors, both at the beginning of the study and thereafter, associated with participation in the GAZEL cohort, set up in 1989 in a large French company. The authors used logistic regression to analyze the associations between participation and data available for both participants (n = 20,093) and nonparticipants (n = 24,829). Higher participation was associated with male sex, marriage, children, managerial status, and residence in particular regions. Among men, lower participation was associated with sick leave in the year before recruitment and afterwards. During follow-up, participation was negatively associated with several groups of diseases, especially those associated with alcohol consumption. The risk of upper respiratory and digestive tract and lung cancer during follow-up was higher among nonparticipants. The same phenomenon occurred among women, but less markedly, for cancers of the breast and genital organs. During follow-up, mortality among men was higher among nonparticipants, especially for alcohol-related diseases. The association among women was less strong. Among men, but not among women, diseases caused by alcohol, smoking, or dangerous behavior were the primary reason for the health differences observed between participants and nonparticipants. Overall, the most important determinants of participation were cultural factors and lifestyle behaviors.

Absenteeism↗
PubMed2001

Annexin A5 D226K structure and dynamics: identification of a molecular switch for the large-scale conformational change of domain III.

The domain III of annexin 5 undergoes a Ca(2+)- and a pH-dependent conformational transition of large amplitude. Modeling of the transition pathway by computer simulations suggested that the interactions between D226 and T229 in the IIID-IIIE loop on the one hand and the H-bond interactions between W187 and T224 on the other hand, are important in this process [Sopkova et al. (2000) Biochemistry 39, 14065-14074]. In agreement with the modeling, we demonstrate in this work that the D226K mutation behaves as a molecular switch of the pH- and Ca(2+)-mediated conformational transition. In contrast, the hydrogen bonds between W187 and T224 seem marginal.

Annexin A5↗
PubMed2001

[ A registry of ischaemic cardiopathies among active workers at Electricité de France-Gaz de France. Program development and first results].

BACKGROUND: The social security department of the French national electric and gas company has established an ischemic heart disease register among a population of about 140 000 employees based on sick leaves as well as deaths recorded with their medical cause. METHODS: History of the illness, medical tests and treatments were known retrospectively from the consulting physicians of the company. Acute coronary events recorded were: inaugural angina pectoris, myocardial infarction, sudden coronary death and fortuitous discovery of coronary disease. RESULTS: A first study conducted on employees during the 1993-1995 period showed infarction incidence age rates similar to those estimated from the French MONICA registers for France as a whole. Regional discrepancies were observed for myocardial infarction rates: Nord-Pas de Calais, Champagne-Ardennes, Lorraine, Franche-Comté and Limousin were at the most elevated risk (SIR=131, 155, 169, 125 and 178 resp). Large variations according to socio-economic status were observed. CONCLUSION: This register will permit studies on the links between socio-economic status at different professional career points and the occurrence of ischemic heart disease and the evaluation of the impact of psychosocial factors such as previous depressive disorders.

Absenteeism↗