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Biomedical subjects

L Chatenoud

Publications and source records attributed to L Chatenoud.

At least 19 recordsLinked to original sources

[Thyroiditis and gluten intolerance: extrapancreatic auto-immune diseases associated with type 1 diabetes].

OBJECTIVES: This study aimed at evaluating the screening of thyroïditis and coeliac disease, in a population of children and adolescents with type 1 diabetes, and at comparing the appearance of antibodies specific for these 2 diseases as a function of age. PATIENTS AND METHODS: The study included 370 children and adolescents, 179 girls and 191 boys, aged 13.8 +/- 4.4 yr and with diabetes for 7.1 +/- 3.8 yr. Auto-immune thyroïditis was screened using antimicrosomal and antithyroglobulin auto-antibodies, at a mean rhythm of 3 tests per patient (1 every 2 yr), associated with dosages of TSH and FT4. Coeliac disease was screened using antigliadin (+/- antiendomysium) auto-antibodies, at a mean rhythm of 2 tests per patient, and was confirmed by duodenojejunal biopsy. Antithyroïd auto-antibodies were correlated with age following the "censured data analysis" type approach. RESULTS: Antithyroïd autoantibodies were found in 42 patients (11.4%), of whom 9 were treated for hypothyroïdism and 1 for Basedow disease, and coeliac disease autoantibodies were found in 9 patients (3.2% of tested patients). The cumulated frequency of antithyroïd auto-antibodies increased regularly with age and was significantly higher in girls, reaching 28% in girls and 12% in boys around 18 yr of age. As a consequence of this evolution, antithyroïd auto-antibodies were frequently found at the time of diagnosis of diabetes when it declared after 10 yr of age, while they often became positive secondarily when diabetes occurred before 10 yr of age. Coeliac disease specific auto-antibodies appeared much earlier and were found at the time of diagnosis of diabetes or at the first screening test. CONCLUSION: Antithyroïd autoantibodies are increasingly frequent with age in children with type 1 diabetes, and become very elevated in girls. The rhythm for screening should be adapted to this evolution of autoantibodies with age, which is very different between thyroïditis and coeliac disease.

Adolescent↗

Alcohol drinking and risk of small for gestational age birth.

OBJECTIVE: To assess if alcohol drinking is a risk factor for small for gestational age (SGA) birth. METHODS: Case-control study. Cases were 555 women (mean age 31 years, range 16-43) who delivered SGA babies at the Clinica Luigi Mangiagalli and the Obstetric and Gynecology Clinic of the University of Verona. The controls were 1966 women (mean age 31 years, range 14-43) who gave birth at term (> or =37 weeks of gestation) to healthy infants of normal weight at the hospitals where cases had been identified. RESULTS: No increase in the risk of SGA birth was observed in women drinking one or two drinks/day in pregnancy, but three or more per day increased the risk: odds ratios (OR) were 3.2 (1.7-6.2) for > or =3 drinks during the first trimester, 2.7 (1.4-5.3) during the second and 2.9 (1.5-5.7) during the third. CONCLUSIONS: The study shows an increased risk of SGA births in mothers who drink > or =3 units/day of alcohol in pregnancy.

Adolescent↗

Coffee drinking and risk of preterm birth.

OBJECTIVES: We analysed the association between coffee drinking before and during the three trimesters of pregnancy and the risk of preterm birth of babies normal for gestational age (NGA) or small for gestational age (SGA). METHODS: Case-control study conducted in University clinics of North Italy. Cases were 502 women who delivered at <37 weeks of gestation. The controls included 1966 women who gave birth at term (>or=37 weeks of gestation) to healthy infants on randomly selected days at the hospitals where cases had been identified. RESULTS: There was inverse association for coffee consumption in the third trimester of pregnancy in SGA cases compared to NGA (heterogeneity test between OR: chi1(2)=5.6811 P<0.05). In comparison with not drinkers, all the ORs of overall intake of caffeine were closed near the unity for both SGA and NGA preterm birth. CONCLUSION: Compared with no consumption, a low consumption of coffee during pregnancy may not have significant effects on preterm birth.

Adolescent↗

Trends in mortality from coronary heart and cerebrovascular diseases in the Americas: 1970-2000.

OBJECTIVE: To describe trends in mortality from coronary heart disease (CHD) and cerebrovascular accidents (CVAs) over the period 1970 to 2000 in the Americas. METHODS: Age standardised mortality rates were derived from the World Health Organization database and grouped according to the International classification of diseases, ninth revision. Joinpoint analysis was used to identify changes in trends. RESULTS: In the USA and Canada, CHD mortality rates declined by about 60% in both sexes. In Latin America, falls in CHD mortality were observed for Argentina, Brazil, Chile, Cuba, and Puerto Rico. In 2000, mortality rates among men were highest in Venezuela (137.3/100,000) and lowest (apart from Ecuador) in Argentina (63.5/100,000). For women, the rates were highest in Cuba (79.4/100,000) and lowest in Argentina (26.5/100,000). For CVA mortality, a decline by about 60% was observed in the USA and Canada for both sexes. The falls were smaller (about -25% to -40% among men and -20% to -50% among women) in Puerto Rico, Argentina, Chile, and Costa Rica and only minor in Ecuador, Mexico, and Venezuela. Around 2000, CVA mortality in Latin America was highest in Brazil (85.5/100,000 among men and 61.7/100,000 among women) and lowest in Puerto Rico (29.3/100,000 among men and 24.1/100,000 among women). CONCLUSIONS: Recent falls in CHD and CVA were less favourable in Latin America than in the USA and Canada. This may reflect unfavourable changes in nutrition (including obesity), physical activity, and smoking in most Latin American countries, together with less effective control of hypertension and management of the diseases.

Adult↗

Trends in cancer mortality in the Americas, 1970-2000.

BACKGROUND: Data and statistics on cancer mortality over the last decades are available for most developed countries, while they are more difficult to obtain, in a standardized and comparable format, for countries of Latin America. PATIENTS AND METHODS: Age standardized (world population) mortality rates around the year 2000, derived from the WHO database, are presented for 14 selected cancers and total cancer in 10 countries of Latin America, plus, for comparative purposes, Canada and the USA. Trends in mortality are also given over the period 1970-2000. RESULTS: In 2000, the highest total cancer mortality for males was observed in Argentina and Chile, with rates comparable to those of Canada and the USA, i.e. about 155/100,000. For women, Chile and Cuba had the highest rates in Latin America (114 and 103/100,000, respectively), again comparable to those of North America (around 105/100,000). These reflect the comparatively high mortality from cancer of the stomach (for Chile), lung and intestines (for Argentina) in men, and of stomach and uterus (for Chile), intestines and lung (for Cuba) in women. Colombia, Ecuador and Mexico had the lowest total cancer mortality for men, due to low mortality from stomach, colorectal and lung cancer. For women, the lowest rates were in Brazil and Puerto Rico, reflecting their low stomach and cervical cancer rates. In Argentina, Chile, Colombia, Costa Rica and Venezuela cancer mortality rates tended to decline, particularly in men. Rates were stable in Ecuador and Puerto Rico, and were increasing in Mexico and Cuba. CONCLUSIONS: Mortality from some common cancers (including colorectal and lung) is still low in Latin America compared with Canada and the USA, and decreasing trends have been observed in the last decades for some cancer sites (including stomach, uterus, lung and other tobacco-related cancers) in several countries. However, mortality from female lung and breast cancers has been increasing in most countries of Latin America, and several countries still show an extremely elevated mortality from cancer of the cervix. Selected neoplasms amenable to treatment, including testis and leukemias, also show unsatisfactory trends in Latin America.

Adult↗

Maternal coffee drinking in pregnancy and risk of small for gestational age birth.

OBJECTIVE: We have analysed the association between coffee drinking before and during the three trimesters of pregnancy and risk of small for gestational age (SGA) birth. METHODS: Cases were 555 women who delivered SGA births (ie <10th percentile according Italian standard). The controls included 1966 women who gave birth at term (>/=37 weeks of gestation) to healthy infants of normal weight. RESULTS: In comparison with nondrinkers, the ORs for SGA birth were 1.3 (95% confidence interval, CI, 0.9-1.9) for consumption of four or more cups of coffee/day before pregnancy, and 1.2 (95% CI 0.8-1.8), 1.2 (95% CI 0.8-1.8) and 0.9 (95% CI 0.6-1.4) for consumption of three or more cups of coffee/day during the first, second and third trimester of pregnancy, respectively. CONCLUSION: These findings were consistent in women who delivered preterm and at term births and were not affected by potential confounding such as smoking.

Adolescent↗

Selected food intake and risk of endometriosis.

BACKGROUND: To offer data on the relationship between diet and risk of pelvic endometriosis, we analysed data collected in the framework of two case-control studies. METHODS: Data from two case-control studies conducted in Northern Italy between 1984 and 1999 were combined. Cases were 504 women aged < 65 years (median age 33 years, range 20-65) with a laparoscopically confirmed diagnosis of endometriosis, admitted to a network of obstetrics and gynaecology departments in Milan, Brescia and Pavia. Controls were 504 women (median age 34 years, range 20-61) admitted for acute non-gynaecological, non-hormonal, non-neoplastic conditions. RESULTS: Compared to women in the lowest tertile of intake, a significant reduction in risk emerged for higher intake of green vegetables [odds ratio (OR) = 0.3 for the highest tertile of intake] and fresh fruit (OR = 0.6), whereas an increase in risk was associated with high intake of beef and other red meat (OR = 2.0) and ham (OR = 1.8). Consumption of milk, liver, carrots, cheese, fish and whole-grain foods, as well as coffee and alcohol consumption, were not significantly related to endometriosis. CONCLUSIONS: This study suggests a link between diet and risk of endometriosis.

Adult↗

Infections and atopy: an exploratory study for a meta-analysis of the "hygiene hypothesis".

BACKGROUND: According to the "hygiene hypothesis" selected allergic diseases could be prevented by exposure to infectious agents during early childhood. METHODS: This study was performed to assess the feasibility of a future meta-analysis on the "hygiene hypothesis" and atopic diseases. Differences concerning the potential association with a history of infectious events, in terms of magnitude and homogeneity of global risk estimates between the three major atopic diseases (i.e. atopic dermatitis, asthma and allergic rhinitis) were examined. We conducted a preliminary analysis on a sample of articles published on this topic and cited in a recent and authoritative review. RESULTS: The ranges of relative risks estimates (between 0.6 and 0.8) were similar for atopic dermatitis, allergic rhinitis and asthma. Compared with asthma and allergic rhinitis, reported global risk estimates were more stable for atopic dermatitis (lowest heterogeneity). Our analysis suggests that three main categories of indirect markers of exposure to infection can be identified: 1) geographical gradient, 2) indices of potential contact with infectious agents (such as number of siblings) and 3) history of infectious events. CONCLUSIONS: In this exploratory study, we chose articles cited in a single review and obtained a preliminary quantification of the association between infections and atopic diseases. The association with indirect markers of infection corresponded to 20% protection for atopic dermatitis, 30% for allergic rhinitis and 40% for asthma. In a subsequent meta-analysis, diseases should be considered separately and differences between types of exposures should be taken into account as one of the major end-points, with attention to time since exposure and disease onset.

Asthma↗

Trends in cancer mortality in Mexico, 1970-1999.

BACKGROUND: Few data on cancer mortality have been published for Mexico over the last few decades. It is therefore of interest to conduct a systematic and updated analysis of cancer mortality in this country. PATIENTS AND METHODS: Age-standardised (world population) mortality rates, at all ages and truncated at age 35-64 years, from major cancers and all cancers combined were computed on the basis of certified deaths derived from the World Health Organization database for the period 1970-99. RESULTS: Mortality rates for all neoplasms showed an upward trend in men of all ages (from 58.2/100,000 in 1970-74 to 87.1/100,000 in 1995-99) and in middle-aged men (from 76.1 to 93.7/100,000, respectively). This reflects the rise until the early 1990s in lung cancer mortality (from 8.1/100,000 in 1970-74 to 15.6/100,000 in 1995-99) and prostate cancer (from 5.5 to 12.2/100,000, respectively). In women, overall mortality rates showed an increase between the early 1970s (75.4/100,000) and the late 1990s (82.3/100,000). Total cancer mortality rates remained low, however, compared with other American countries (e.g. 153.3/100,000 men and 108.6/100,000 women in 1999 in the United States). Truncated rates were stable (126.5/100,000 in 1970-74 and 125.8/100,000 in 1995-99), although they were much higher than overall rates, reflecting exceedingly high rates for uterine (mostly cervical) cancer mortality in middle-aged women (29.5/100,000 in 1995-99). CONCLUSIONS: Total cancer mortality in Mexico has remained comparably low on a worldwide scale, and the upward trends in mortality rates for lung and other tobacco-related neoplasms have tended to level off over the last decade. However, steady rises have been observed for other major cancers, including prostate and breast. Cervical cancer remains a major health problem in women.

Adult↗

Moderate alcohol drinking and risk of preterm birth.

OBJECTIVE: We have analysed the association between alcohol drinking before and during the three trimesters of pregnancy and risk of preterm birth of babies with normal weight for gestational age or with low weight for gestational age (SGA). DESIGN: Case-control study. SETTING: General and university hospitals in Italy. SUBJECTS: Cases were 502 women who delivered preterm births <37 weeks gestation. The controls included 1966 women who gave birth at term (>/=37 weeks of gestation) to healthy infants of normal weight (ie between 10th and 90th centile according to the Italian standard) on randomly selected days at the hospitals where cases had been identified. INTERVENTIONS: Interview. RESULTS: No increased risk of preterm birth was observed in women drinking one or two drinks/die in pregnancy, but three or more drinks/die increased the risk (multivariate odds ratios (OR) 2.0 for >/=3 drinks during the first trimester, 1.8 during the second and 1.9 during the third). When the analysis was conducted separately for preterm births with normal weight or SGA, the increased risk was observed in preterm SGA only (multivariate OR for >/=3 drinks/die during the first trimester=3.6, 95% confidence interval (CI) 1.3-11.1); the estimated multivariate OR for >/=3 drinks/die during the first trimester of preterm babies with normal weight for gestational age was only slightly above unity and not statistically significant (multivariate OR 1.4, 95% CI 0.5-3.7). CONCLUSIONS: The study shows an increased risk in mothers who drink >/=3 die units alcohol in pregnancy of preterm births.

Adult↗

The activity of immunoregulatory T cells mediating active tolerance is potentiated in nonobese diabetic mice by an IL-4-based retroviral gene therapy.

Splenocytes from nonobese diabetic mice overexpressing murine IL (mIL)-4 upon recombinant retrovirus infection lose their capacity to transfer diabetes to nonobese diabetic-scid recipients. Diabetes appeared in 0-20% of mice injected with mIL-4-transduced cells vs 80-100% of controls injected with beta-galactosidase-transduced cells. Protected mice showed a majority of islets (60%) presenting with noninvasive peri-insulitis at variance with beta-galactosidase controls that exhibited invasive/destructive insulitis. Importantly, in all recipients, the transduced proteins were detected within islet infiltrates. Infiltrating lymphocytes from recipients of mIL-4-transduced cells produced high levels of mIL-4, as assessed by ELISA. In recipients of beta-galactosidase-transduced cells, approximately 60% of TCRalphabeta(+) islet-infiltrating cells expressed beta-galactosidase, as assessed by flow cytometry. The protection from disease transfer is due to a direct effect of mIL-4 gene therapy on immunoregulatory T cells rather than on diabetogenic cells. mIL-4-transduced purified CD62L(-) effector cells or transgenic BDC2.5 diabetogenic T cells still transferred disease efficiently. Conversely, mIL-4 transduction up-regulated the capacity of purified immunoregulatory CD62L(+) cells to inhibit disease transfer. These data open new perspectives for gene therapy in insulin-dependent diabetes using T cells devoid of any intrinsic diabetogenic potential.

Adjuvants, Immunologic↗

Oral contraceptives and colorectal cancer risk: a meta-analysis.

Several studies have suggested an inverse association between use of combined oral contraceptives (OC) and the risk of colorectal cancer and here we present a meta-analysis of published studies. Articles considered were epidemiological studies published as full papers in English up to June 2000 that included quantitative information on OC use. The pooled relative risks (RR) of colorectal cancer for ever OC use from the 8 case-control studies was 0.81 (95% confidence interval (CI): 0.69-0.94), and the pooled estimate from the 4 cohort studies was 0.84 (95% CI: 0.72-0.97). The pooled estimate from all studies combined was 0.82 (95% CI: 0.74-0.92), without apparent heterogeneity. Duration of use was not associated with a decrease in risk, but there was some indication that the apparent protection was stronger for women who had used OCs more recently (RR = 0.46; 95% CI: 0.30-0.71). A better understanding of this potential relation may help informed choice of contraception.

Case-Control Studies↗

In vivo blockade of the Fas-Fas ligand pathway inhibits cyclophosphamide-induced diabetes in NOD mice.

There is compelling evidence to show that insulin dependent diabetes ensues from selective apoptosis of pancreatic beta-cells mediated by autoreactive T-lymphocytes. The respective implication in this phenomenon of the various apoptotic pathways driven by Fas, perforin, or tumor necrosis factor is still ill- defined. Here we took advantage of the cyclophosphamide-induced model of accelerated diabetes in NOD mice to explore the physiopathological role of the Fas-Fas Ligand pathway. A single injection of cyclophosphamide (200 mg/kg) to 7-8 week-old prediabetic NOD mice triggered diabetes within 10-15 days in 85-100% of the animals. Cyclophosphamide also induced a significant decrease in spleen T cells, that was most evident by days 6-10 after treatment, and selectively affected the CD3(+)CD62L(+)compartment that includes immunoregulatory T cells. To block the in vivo Fas-Fas ligand (Fas L) interaction we administered a biologically active recombinant fusion protein coupling mouse Fas to the Fc portion of human IgG1 (FAS-Fc). Mice treated with FAS-Fc (10 doses iv of 15 microg) starting on the day of cyclophosphamide injection up to day 22, were fully protected from disease. Unexpectedly this protective effect was not due to blockade of Fas-FasL-mediated beta-cell apoptosis but rather to the inhibition of the cyclophosphamide effect on T cells. Indeed FAS-Fc treatment prevented the drug-induced T cell depletion in general and that of immunoregulatory T cells in particular. Additionally, FAS-Fc administration limited to the phase of beta-cell destruction did not afford any protection.

Animals↗

Restoration of self-tolerance is a feasible approach to control ongoing beta-cell specific autoreactivity: its relevance for treatment in established diabetes and islet transplantation.

Major progress has been made over the last 10 years in understanding the immune mechanisms underlying autoimmune Type I (insulin-dependent) diabetes mellitus. It seems that immunotherapy is the best approach for preventing and/or arresting beta cell destruction. For immunotherapeutic approaches to be clinically applicable to Type I diabetes, they cannot rely on the use of non-specific immunosuppressants. Their relative ineffectiveness over the long term and the risk of recurrence, once the drug is withdrawn, requires permanent drug treatment which augments problems of infection and drug toxicity. One solution is to selectively tackle the pathogenic immune response. Operationally, this requires establishing immunological tolerance, i.e. a state of durable antigen-specific unresponsiveness in the absence of generalised immunosuppression. This review aims to present the rationale and clinical applicability of possible immunointervention strategies in Type I diabetes aimed at restoring self-tolerance to beta cells.

Animals↗

Dietary factors and risk of spontaneous abortion.

OBJECTIVE: This study examines the association between dietary habits and risk of spontaneous abortion. DESIGN: Hospital-based case-control study. SETTING: Obstetric hospitals in Milan, Italy. SUBJECTS: Cases were: 912 women admitted for spontaneous abortion (within the 12th week of gestation). Controls were: women who gave birth at term to healthy infants on randomly selected days at the same hospitals where cases had been identified. RESULTS: The risk of spontaneous abortion was inversely and significantly related to green vegetables, fruit, milk, cheese, eggs and fish consumption. The multivariate odds ratios (OR), for highest versus lowest levels of intake, were 0.3 for fruit, 0.5 for cheese, 0.6 for green vegetables and milk and 0.7 for fish and eggs. The major type of seasoning fats have showed a direct association with risk of miscarriage. Comparing the highest with the lowest intake, the ORs were 2.0 (95% confidence interval, CI 1.1-3.6) and 1.6 (95% CI 1.1-2.3) for butter and oil, respectively. No consistent association emerged between meat, liver, ham and carrots intake and the risk of spontaneous abortion. CONCLUSIONS: This result suggests that a diet poor in several aspects, including vegetables and fruit, milk and dairy products, but rich in fats, may be a determinant or a correlate of increased risk of spontaneous abortion.

Abortion, Spontaneous↗

Dietary fibres and ovarian cancer risk.

Data from an Italian multicentre case-control study on ovarian cancer were used to analyse the relationship between various types of fibres and ovarian cancer risk. The study, conducted between 1992 and 1999, included 1031 cases of incident, histologically-confirmed epithelial ovarian cancer. Controls were 2411 women admitted to the same network of hospitals for acute, non-malignant, non-hormonal-related diseases. Cases and controls were interviewed using a validated food frequency questionnaire (FFQ). Odds ratios (ORs), and the corresponding 95% confidence intervals (CI), were estimated using unconditional multiple logistic regression models. For total (Englyst) fibre, the OR for the highest versus the lowest quintile of intake was 0.68, and the continuous OR for the difference between the 80th and the 20th percentile of intake was 0.87. For most types of fibre, the continuous OR was significantly below 1. The OR was 0.83 for cellulose, 0.89 for soluble non-cellulose polysaccharides (NCPs), 0.86 for total insoluble fibre, 0.92 for insoluble NCP, and 0.95 (non-significant) for lignin. The inverse association was consistent across strata of age, family history and menopausal status, even if the association was apparently stronger in postmenopausal women. When fibre was classified according to the source, vegetable (but not grain) fibres, showed a significant protective effect, with an OR of 0.78.

Adult↗

Trends in asthma mortality in Italy and Spain, 1980-1996.

Asthma is a major public health problem, with variable trends in several countries. We analysed mortality trends from asthma in Italy and Spain between 1980 and 1996. Overall asthma-related mortality at all ages increased between 1980 and 1987 in both sexes in Italy, from 16.6 in 1980-1981 to 29.0 in 1986-1987 per million males, and from 8.0 in 1980-1981 to 13.8 in 1986-1987 per million females, but decreased thereafter to reach 14.6 per million in males and 8.7 in females in 1996. The downward trends after 1987 were consistent in middle age and elderly population, but asthma mortality tended to rise in children and young adults over the last few years. In Spain, overall age-standardized mortality rates from asthma declined in men from 37.8 in 1980-1981 to 10.1 in 1996, and from 19.5 in 1980-1981 to 13.2 per million females in 1996. In women, the fall in mortality rates was smaller, and overall mortality was higher than in males since early 1990s. Trends of asthma mortality in Italy and Spain were favourable over the last decade.

Adolescent↗