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Biomedical subjects

M Goldberg

Publications and source records attributed to M Goldberg.

At least 37 records · Page 2Linked to original sources

Is the lingual forming part of the incisor a structural entity? Evidences from the fragilitas ossium (fro/fro) mouse mutation and the TGFbeta1 overexpressing transgenic strain.

Our objective was to study the teeth of a mutant mice fro/fro that display severe forms of osteogenesis imperfecta. One day and 8 week-old fro/fro and +/fro heterozygote mice (wild type, WT) were processed for light and scanning electron microscopy. The genetic defect, shown to be located on chromosome 8, induced alveolar bone and teeth hypomineralisation. Due to defective cell proliferation in the fro/fro, the distal growth of the mandibular incisors was impaired. Immunolabelling revealed an increase of chondroitin/dermatan sulphate, whereas no difference was detected in dental tissues for decorin and biglycan. Amelogenin expression was decreased in the incisor and enhanced in the molar. Dentin sialoprotein was below the level of detection in the fro/fro, whereas osteonectin and osteopontin were unchanged. The main target of the mutation was seen in the lingual part of the incisor near the apex where dentine formation was delayed. In the molars, bulbous roots with obliteration of the pulp chamber were seen. In the TGFbeta1 overexpressing mice, the lingual root-analogue part of the incisor was missing. In the molar, short roots, circumpulpal dentine of the osteodentine type and pulp obliteration were seen. It may be noted that, although the mutant and transgenic strains mutations are two different genetic alterations not related to the same defective gene, in both cases the expression of the dentin sialoprotein is altered. Altogether, the present data suggest that the lingual forming part of the incisor seems to be an anatomical entity bearing its own biological specificities.

Amelogenin↗

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↗

[Use of a job-exposure matrix for the screening of occupational exposure to asbestos].

BACKGROUND: According to a recent French legislation (1995), retired people who have been exposed to an occupational carcinogen can benefit from a specific post-occupational medical follow-up program, supported by the "Caisse Primaire d'Assurance-Maladie" (CPAM), the French health insurance system. However, only very few people presently take access to this social measure. The ESPACES project developed and evaluated a procedure to identify retirees who have been exposed to asbestos during their career, and to inform them about the post-occupational medical follow-up program. METHODS: This pilot study was performed within the health centers ("Centres d'examens de santé" (CES)) of the health insurance system in a random sample of men who have retired from the six main French administrative divisions between 1994 to 1996. A probability of exposure to asbestos was attributed through a job exposure matrix. Subjects were interviewed in the CES to validate their exposure data. Retired subjects with confirmed exposure to asbestos were referred to their CPAM, to apply for the medical follow-up. The whole process was evaluated through a comparison with control CPAMs, and simulations were performed to assess its sensitivity and specificity, as well as the total number of persons in France who could potentially benefit. RESULTS: Among the 737 persons classified as exposed by the matrix who came to the CES, the exposure was confirmed for 53.8%, and 143 benefited from the medical follow-up, 17 times more than in a sample of control CPAMs. Based on an annual number of about 250,000 new retirees, simulations showed that a low detection threshold, taking into account the probability and duration of exposure, would yield approximately 25,000 persons coming to the CES, more 6,000 of them benefiting from the follow-up. CONCLUSION: The proposed detection threshold would allow for a feasible and ethically acceptable generalization, due to the optimization of the false negative and false positive rate.

Asbestos↗

A novel per-oral insulin formulation: proof of concept study in non-diabetic subjects.

AIMS: The aim of our study was to examine the absorption of insulin from the gastrointestinal (GI) tract, using a novel oral formulation-adding a delivery agent SNAC (sodium N-[8-(2-hydroxybenzoyl)amino] caprylate) in combination with insulin. METHODS: Capsules containing insulin and SNAC, in various combinations, were administered orally, as a single dose, to 12 non-diabetic subjects and four control subjects (receiving SNAC or insulin only) in order to assess its biological effect and safety. Plasma glucose levels, insulin and C-peptide concentrations, as well as SNAC levels, were determined, at timed intervals up to 4 h. RESULTS: In all cases, a glucose-lowering effect was demonstrated, preceded by an increase in plasma insulin levels. The nadir of plasma glucose levels appeared after 30-50 min, following the ingestion of the mixture. The plasma insulin levels were found to parallel the blood SNAC levels. Plasma C-peptide levels were suppressed by the lowered glucose levels achieved concurrent with the increasing amount of exogenous insulin absorbed, indicating that the secretion of endogenous hormone was partially abolished. There were no biological effects regarding blood glucose levels upon administration of SNAC or insulin when given alone. No adverse effects were detected during the trial or several weeks after the trial. CONCLUSIONS: Insulin in combination with a novel delivery agent, SNAC, given orally, is absorbed through the GI tract in a biologically active form. This was demonstrated by a glucose lowering effect of the mixture as well as a suppression of an endogenous insulin secretion.

Absorption↗

Using a representative sample of workers for constructing the SUMEX French general population based job-exposure matrix.

BACKGROUND: Job-exposure matrices (JEMs) applicable to the general population are usually constructed by using only the expertise of specialists. AIMS: To construct a population based JEM for chemical agents from data based on a sample of French workers for surveillance purposes. METHODS: The SUMEX job-exposure matrix was constructed from data collected via a cross-sectional survey of a sample of French workers representative of the main economic sectors through the SUMER-94 survey: 1205 occupational physicians questioned 48 156 workers, and inventoried exposure to 102 chemicals. The companies' economic activities and the workers' occupations were coded according to the official French nomenclatures. A segmentation method was used to construct job groups that were homogeneous for exposure prevalence to chemical agents. The matrix was constructed in two stages: consolidation of occupations according to exposure prevalence; and establishment of exposure indices based on individual data from all the subjects in the sample. RESULTS: An agent specific matrix could be constructed for 80 of the chemicals. The quality of the classification obtained for each was variable: globally, the performance of the method was better for less specific and therefore more easy to assess agents, and for exposures specific to certain occupations. CONCLUSIONS: Software has been developed to enable the SUMEX matrix to be used by occupational physicians and other prevention professionals responsible for surveillance of the health of the workforce in France.

Algorithms↗

TEGDMA modulates glutathione transferase P1 activity in gingival fibroblasts.

Dental resinous materials can contain large amounts (from 30 to 50%) of triethylene-glycol-dimethacrylate (TEGDMA). This compound leaches into aqueous media and is toxic to dental pulp, as well as to gingival fibroblasts in vitro. To elucidate the mechanism of TEGDMA toxicity, we investigated the effects on glutathione (GSH) level and glutathione transferase P1 (GSTP1) activity in cultured human gingival fibroblasts. TEGDMA cytotoxic concentrations (from 0.5 to 2 mM) induced a depletion of GSH without formation of oxidized GSH (GSSG). In fibroblasts expressing the wild-type GSTP1, TEGDMA both inhibited and potentiated GSTP1 activity at high (IC50 = 1.1 mM) and low concentrations, respectively. In contrast, cells expressing the GSTP1 *A/*B variant showed a weak inhibition of GST activity only, associated with greater sensitivity to drug toxicity. Biochemical analysis of GSTP1 inhibition revealed that TEGDMA is a non-competitive antagonist with respect to GSH and substrate. Thus, TEGDMA interference with GSH and GSTP1 activity may contribute to dental-resin-induced adverse effects.

Cell-Free System↗

Radiotherapy patterns of care study in lung carcinoma.

PURPOSE: For the first time, a lung Patterns of Care Study was conducted to determine the national patterns of radiation (RT) practice in patients treated for nonmetastatic lung cancer in 1998 to 1999. MATERIALS AND METHODS: A national survey of randomly selected RT institutions in the United States was conducted using two-stage cluster sampling, stratified by practice type. Patients with nonmetastatic lung cancer (Karnofsky performance score [KPS] > or = 60), who received RT as definitive or adjuvant therapy, were randomly selected. To determine national estimates, sample size was weighted by the relative number of institutions per strata and the number of patient records reviewed per the number of patients eligible. Accordingly, 42,335 patient records from 58 institutions were reviewed by trained research associates. The unweighted sample size (or number of patients) was 541. RESULTS: The histologies were small-cell lung cancer (SCLC) in 14.5% of patients versus non-small-cell lung cancer (NSCLC) in 85.5% of patients. The median age was 67 years (range, 29 to 92 years); 61% of patients were male, and 38% were current smokers. Bone scans and brain imaging were not obtained in 34% and 52% of clinical stage (CS) III NSCLC patients, respectively. Regarding treatment strategies, for SCLC and CS III NSCLC, chemotherapy plus RT was used significantly more than RT alone (P <.05); in CS I NSCLC, RT alone was the primary treatment (P <.05). Overall, 58% of patients received systemic therapy. On multivariate analysis, factors correlating with increased use of chemotherapy included younger age, histology (SCLC > NSCLC), increasing CS, increasing KPS, and lack of comorbidities. Only 3% of all patients were treated on prospective clinical trials. CONCLUSION: This study establishes the general patterns of care for lung carcinoma in RT facilities within the United States. As supported by clinical trials, patients with limited-stage SCLC and CS III NSCLC received chemotherapy plus RT more than they received RT alone. Further improvements in staging, smoking cessation, and increased accrual to clinical trials must be encouraged.

Adult↗

In vitro effects of ascorbate and Trolox on the biocompatibility of dental restorative materials.

Previous in vitro studies on the cytotoxicity of eight dental restorative materials including composites, compomers, resin-modified glass ionomer cements and glass ionomer cements have demonstrated a depletion of intracellular glutathione in gingival fibroblasts incubated with eluates of these materials and a protective effect of N-acetylcysteine. In the present study, we investigate the effects of two other antioxidants: ascorbate and Trolox. It was found that Trolox reduced the cytotoxicity induced by resin-based biomaterial eluates. In contrast, ascorbate increased in a dose-dependent manner the toxic effect of all eluates except for Z100 MP and Tetric flow (composites). The effect of D-mannitol was studied for GC FUJI II and was found to neutralize the additional toxic effect of ascorbate. Ascorbate increased the depletion of intracellular glutathione of these dental material eluates (between 17% and 24%, depending on the material). Quantification of metal ions in the dental material eluates showed the presence of significant amounts of aluminum and iron in GC FUJI II > photac fil > GC FUJI II LC > F2000. The mechanism of this increased cytotoxicity could be explained by the Fenton reaction resulting from the pro-oxidant effect of ascorbate in the presence of iron (transition metal ions) and/or aluminum.

Aluminum↗

Neonatologists are using much less dexamethasone.

Two historical cohorts (1993-1994 and 2001) of preterm infants ventilated for respiratory distress syndrome were compared. Dexamethasone administration fell from 22% to 6%. Chronic lung disease in survivors rose slightly from 13% to 17%, and mortality fell from 21% to 15% (other causes). The effect of restriction of dexamethasone use on chronic lung disease and mortality remains to be seen.

Birth Weight↗

Occupational mobility and risk factors in working men: selection, causality or both? Results from the GAZEL study.

OBJECTIVE: To explore the relation between risk factors (RF) and occupational mobility in working men. SETTING: 20 000 volunteers working at the French National Electricity and Gas Company (GAZEL cohort). PARTICIPANTS: Men aged 43 to 53 years in 1992. DESIGN: Three designs were used for analysis. (1) The association between occupational mobility experienced before 1992 and RF reported at that date was analysed among 10 383 men. (2) The predictive role of RF on occupational mobility over 1992-1999 was studied in a subsample of 4715 men. (3) Reciprocally, occupational mobility in 1985-1992 was analysed in relation to RF changes over 1993-1999. MAIN OUTCOME MEASURES: Self reported smoking status, excessive alcohol consumption, arterial hypertension, and overweight. Occupational mobility defined by any upward transition between senior executives and professionals/middle executives/employees, and workers. RESULTS: (1) Cross sectionally, non-mobile men as their entry into the company had a higher risk of being smokers, excessive alcohol drinkers, and overweight in 1992 than mobile men. (2) Longitudinally, smokers and excessive alcohol drinkers in 1992 had a higher risk of non-mobility than, respectively, non-smokers and non-excessive alcohol drinkers. (3) Non-mobile men in 1985-1992 had a higher risk of becoming smokers, excessive alcohol drinkers, and hypertensive in 1993-1999 than upwardly mobile men. CONCLUSION: These results suggest a complex relation between RF and occupational mobility. A high level of RF, particularly health behaviours, might account for a selection process reducing upward occupational mobility. In turn, a lack of upward occupational mobility might be associated with an increased incidence of RF.

Adult↗

Do psychosocial work factors and social relations exert independent effects on sickness absence? A six year prospective study of the GAZEL cohort.

STUDY OBJECTIVES: The objective of this prospective cohort study was to determine whether psychosocial work characteristics and social relations exert independent effects on the incidence of sickness absence in a population of middle aged French employees over six years of follow up. DESIGN: This study included 9631 men and 3595 women participating in the French GAZEL cohort. Social relations (social networks, personal social support, and social relations satisfaction) were measured in 1994 by self report. Psychosocial work characteristics (decision latitude, psychological demands, and social support at work) were ascertained in 1995. Sickness absence data were collected independently. The authors studied the incidence of short (>7 days), intermediate (7-21 days), and long (>21 days) spells of absence from 1995 to 31 December 2001. Rate ratios associated with psychosocial exposures, adjusted on sociodemographic characteristics, and health behaviours, were calculated by means of log-linear Poisson regression. SETTING: A cohort of 20000 employees of France's national gas and electricity company (the GAZEL study). MAIN RESULTS: Among men and women, levels of decision latitude and personal social support below the median predicted 17% to 24% increases in absence rates. Low satisfaction with social relations and low social support at work lead to a 10% to 26% excess in sick leaves among men. No interactive effects were found between the variables under study. CONCLUSIONS: The quality of the work environment and of social relations affect sickness absence over an extended period of follow up. This study supports the hypothesis of independent, not interactive effects.

Adult↗

Evaluation of the quality of coding of job episodes collected by self questionnaires among French retired men for use in a job-exposure matrix.

BACKGROUND: and AIMS: The ESPACES study was intended to identify retirees who may have been, according to their job descriptions, exposed to asbestos during their working lives. As part of this study, we analysed the quality of the occupation and activity sector coding as well as its effect on the subjects' exposure status. METHODS: The occupation and activity sector for a sample of 450 retired men were coded twice (with the second coder blinded to the first result), according to the international codes for industries (ISIC-1975) and occupations (ISCO-1968). For each series, linking the information about a job episode (dates, ISIC code, ISCO code) with the matrix allowed attribution of a probability of asbestos exposure to each episode and each subject. The asbestos exposure in the two series was compared by the kappa reproducibility coefficient. RESULTS: The analysis concerned 425 questionnaires. There was at least one difference in the code for either activity sector (ISIC) or occupation (ISCO) in half the episodes (50.2%). The exposure status estimated by the job-exposure matrix did not change between the series for 84.7% of the subjects. The kappa coefficient was 0.64 for all questionnaires, 0.70 when the questionnaire was coded twice by the same coder, and 0.62 when coded by two different coders. CONCLUSIONS: Despite intra- and inter-differences between coders, the coding of job episodes for the ESPACES study appears satisfactory and hence indicates that the assessment of the subjects' asbestos exposure was assessed without major distortions. This study underlines the usefulness of employing coders specifically trained for this technique.

Asbestos↗

Occupational exposures and lung cancer in New Caledonia.

AIMS: To study the associations between occupational exposures and the risk of lung cancer in New Caledonia. METHODS: All cases diagnosed between January 1993 and December 1995 (228 lung cancers) and 305 population controls were included. Detailed information on lifetime job history, smoking, and other potential risk factors was collected by interview. Occupational exposures were assessed from the questionnaires by an industrial hygienist, without knowledge of case-control status. RESULTS: No significant association was found with exposures related to nickel mining and refining, the main industrial activity in the territory. Among men, an excess risk of lung cancer was found for bus and truck drivers. Increased risks were also observed in men with the highest level of cumulative exposure to cleaning products and inorganic fertilisers. Exposure to field dust was associated with lung cancer risk in both sexes, and risk increased with cumulative exposure level. In some areas tremolite asbestos derived from local outcroppings was used as a whitewash. The association between exposure to field dust and lung cancer was limited to men and women exposed to this whitewash-that is, living in areas where the soil may contain tremolite. CONCLUSION: This study shows several associations between occupational exposures and lung cancer. The findings suggest that exposure to tremolite fibres from cultivated fields may increase the risk of lung cancer in New Caledonia.

Adult↗

Alcohol consumption and marital status of French women in the GAZEL cohort: a longitudinal analysis between 1992 and 1996.

OBJECTIVE: The purpose of this research was to describe women's consumption of alcoholic beverages as it related to their marital status over a 5-year period (1992 through 1996) and to study alcohol consumption around the time of marriage or divorce. METHOD: The study sample comprised 4,782 women who worked for Electricité de France-Gaz de France and belonged to the GAZEL cohort. The relevant variables collected by five successive annual questionnaires included marital status and alcohol consumption characteristics. Marginal models were used, reflecting the fact that the data were not independent. RESULTS: Divorcees and widows drank less than married women as measured in fewer glasses per day and fewer days per week drinking wine. Women in the oldest generation drank more than the younger women. Getting married was accompanied by an increased level of drinking, especially of wine, beginning a year before the wedding and lasting until 4 years after it. Consumption declined briefly during the year after a divorce. CONCLUSIONS: These results may be useful for designing prevention programs aimed at groups of women in the general population in France.

Adult↗

Effectiveness of the SmartMV prototype BeefCam System to sort beef carcasses into expected palatability groups.

This study was conducted to determine the effectiveness of the SmartMV prototype BeefCam Video Imaging System (prototype BeefCam) for classifying beef carcasses into palatability ("certified" or "not certified" as palatable) groups. Carcasses (n = 769) were selected from four beef-packing plants to represent three USDA quality grade groups (Top Choice, TC; Low Choice, LC; and Select, SE). Following chilling, a prototype BeefCam image of the longissimus muscle was obtained for each carcass. Strip loins were collected from the left side of each carcass and aged for 10 d; Warner-Bratzler shear force (WBSF; n = 769) values and consumer panel ratings (hedonic, end-anchored, 9-point ratings for overall like/dislike; n = 500 carcasses) were obtained for cooked steaks. Using information from the images, two regression models were developed to predict the first principal component of WBSF and consumer panel ratings for sorting carcasses based on expected eating quality. Model I used only prototype BeefCam output, whereas Model II used prototype BeefCam output and a coded value for quality grade group. For both models, carcasses with a predicted value of less than 0.0 were certified as producing palatable beef Additional carcasses (n = 292) were evaluated at a fifth and separate packing plant by prototype BeefCam to validate Models I and II. A strip loin was collected from each carcass and WBSF was measured after 14 d of aging. The percentages of validation carcasses that generated tough (WBSF > or = 4.5 kg) steaks were 6.5,5.8,10.7, and 7.9% for, TC, LC, SE, and all carcasses, respectively. Use of Model I certified 51.9, 47.6, 43.8, and 47.3% of TC, LC, SE, and all carcasses, respectively. Of the carcasses certified by use of Model I, 0.0,0.0, 4.1, and 1.4% of TC, LC, SE, and all carcasses, respectively, generated tough steaks. Use of Model II certified 59.7, 47.6, 25.0, and 42.1% of TC, LC, SE, and all carcasses, respectively. Of the carcasses certified by use of Model II, 2.2, 0.0, 3.6, and 1.6% of TC, LC, SE, and all carcasses, respectively, generated tough steaks. For both models, the frequency of carcasses that produced tough steaks in the certified group was lower (P < 0.05) for all validation carcasses sampled compared with that of the original carcass population. Based on the decrease in the frequency of carcasses that produced tough steaks, further development of a commercial BeefCam system is warranted.

Adolescent↗

[Constitution of a bank of biological material in the French Gazel cohort: logistical and practical aspects].

The Gazel cohort was launched in January 1989 among workers of the French national electricity and gas company to form an open and general purpose epidemiological laboratory. More than 20.000 workers (15.000 men, 5.000 women), aged from 35 to 50 volunteered to participate. One of the objectives of this cohort was the constitution of a bank of biological material aiming to collect and preserve various biological samples (serum, plasma, DNA, etc). This paper details the organisation of the bank and presents a feasability study concerning 2.000 volunteers.

Adult↗

Proteoglycans in predentin: the last 15 micrometers before mineralization.

Small leucine-rich proteoglycans (SLRPs) regulate extracellular matrix organization. In order to investigate the distribution and potential functions of decorin, biglycan (BGN), and fibromodulin (3 SLRPs, potentially related to dentinogenesis), we performed light and electron immunochemistry on teeth from rats, and on wild-type and biglycan knockout mice (BGN KO). Immunohistochemical data demonstrate that chondroitin sulfate/dermatan sulfate (CS/DS) and keratan sulfate (KS) distributions displayed reverse gradients in predentin. The decrease of CS/DS labeling from the proximal to the distal predentin contrasted with the sharp decorin increase observed in the distal predentin near the predentin/dentin transition, an effect possibly attributable to the deglycosylation action of stromelysin-1. In contrast, BGN concentration was apparently constant throughout the whole predentin. Additional immunolabelings showed, for the first time, the presence of fibromodulin in predentin. Compared with the wild-type mouse, the mean diameter of collagen fibrils in the BGN KO was smaller in the proximal predentin but larger in the central and distal predentin, the metadentin was broader, and the dentin mineralization appeared altered and heterogeneous. Altogether, our data suggest an important role for BGN in dentin formation and mineralization.

Animals↗

[Epidemiology and social determinants of health inequalities].

BACKGROUND: The general approach of social epidemiology is based on the observation of a strong social stratification of health outcomes within populations: a similar stratification of factors associated with health must therefore also exist according to social status. To explain social differences in health, the natural approach for epidemiologists is to consider an imbalanced distribution of established risk factors according to the social position of individuals. As this approach has largely failed, two main other research areas were recently explored: (i) identification of "new" social risk factors; (ii) research of possible mechanisms of social differences in health. METHODS AND RESULTS: Identification of social risk factors: early events and life course, occupational factors, social relationships (social networks and support, discrimination, neighborhood characteristics), health care. Research of possible mechanisms of social differences in health in the context of specific theoretical frameworks: the materialist model, the psychosocial model and the eco-social model integrating the interaction between individuals'characteristics and their environment. COMPLEX METHODOLOGICAL PROBLEMS: definition and measurement of variables characterizing the social situation of individuals; quantification of social inequalities at population level. Observational methods must often rely on very long-lasting cohorts, and imply statistical methods that account for longitudinal data or are able to manage simultaneously individual and contextual data.

Cohort Studies↗