Biomedical subjects
Publications and source records attributed to L Chatenoud.
The safety of use of the calcium channel blocker nifedipine in pregnancy as it affects child development has not been well evaluated. We report the results, with regard to the safety for children of use of nifedipine in pregnancy, on children followed up at 18 months of age born from women recruited in a study comparing routine treatment with nifedipine compared with no treatment.
OBJECTIVE: To analyze the prevalence and risk factors for erectile dysfunction (ED) in Italy in a cross-sectional study. METHODS: Eligible for the study were men aged 18 years or more, randomly identified by 143 general practitioners among their registered patients during the period January 1996 to February 1997. ED was defined as the impossibility to achieve and maintain an erection sufficient for satisfactory sexual performance. RESULTS: Of the 2, 010 men interviewed, 257 (12.8%) reported ED. The prevalence increased with age, from 2% in men aged 18-39 to 48% in those >70 years (tested for trend, p = 0.0001). A history of cardiopathy, diabetes, hypertension, neuropathy, thrombotic/hemorrhagic stroke, peripheral vascular disorders, pelvic/medullary injury and pelvic surgery/radiation all increased the risk of ED. The association of hypertension and diabetes tends to increase the risk of ED. In comparison with nondiabetic and nonhypertensive men, the odds ratio (OR) was 1.4 (95% confidence interval (CI), 0.7-3.2) for hypertensive men without diabetes, 4.6 (95% CI, 1.6-13.7) for diabetic men without hypertension and 8.1 (95% CI, 1.2-55.0) for men with diabetes and hypertension. In comparison with never smokers, the OR of ED was 1.7 (95% CI, 1.2-2.4) for current smokers and 1.6 (95% CI, 1.1-2.3) for ex-smokers and increased with duration of the habit. CONCLUSIONS: The study offers a quantitative estimate of the prevalence of ED and of its main risk factors in Italian men.
OBJECTIVE: The aim of the study was to analyze determinants of age at menopause and hormone replacement therapy (HRT) use. Women included were identified in a large cross-sectional study into epidemiology of the menopause among a sample of women visiting their general practitioners, conducted in Italy. METHODS: Eligible women were identified among consecutive patients, aged 44-66 years, who visited their general practitioner for a general health check-up during the period May-November 1997. A total of 16,916 postmenopausal women were identified by 1123 general practitioners. RESULTS: Overall, the mean age at menopause was 50.2 (SD 3.8) years. Ever-married women reported a slightly higher age at spontaneous menopause than that of never-married women. The finding was significant, but the difference was small. Smoking women reported a younger age at menopause. No clear association emerged between age at menopause, physical activity and body mass index (BMI). A total of 3515 women (20.8%) reported HRT ever-use; the mean duration of use was 3.6 years. HRT use was more frequent among women of higher socioeconomic status, those with a lower BMI and smokers. In particular, in comparison with women reporting a BMI of < 25 kg/m2, the odds ratio (OR) of HRT use was 0.7 (95% confidence interval (CI) 0.7-0.8) and 0.5 (95% CI 0.4-0.6), respectively, in women with a BMI of 25-28 kg/m2 and > or = 29 kg/m2. No association emerged between alcohol consumption, level of physical activity and HRT use. Diabetic women reported HRT use less frequently than non-diabetic women. Likewise, hypertensive women, and those with a history of cardiovascular disease, were less likely to be HRT users than those not reporting these conditions. Women with a diagnosis of osteoporosis/osteopenia reported HRT use more frequently. CONCLUSION: This study, using a large dataset from an Italian population, has confirmed that smoking is related to age at menopause. It has also demonstrated that HRT is more frequently used by women of higher socioeconomic status, those with low BMI and smokers. Diabetes is associated with less frequent use of HRT; conversely, osteoporosis/osteopenia is associated with more frequent HRT use.
BACKGROUND: Several studies reported data on the increased risk of erectile dysfunction (ED) in populations of diabetic men, but few presented data separately for Type 1 and Type 2 subjects. No comparison data for these diabetic subgroups are available with regard to risk factors for ED. METHODS: Eligible for the study were men aged 20-69 years with a diagnosis of insulin-dependent (Type 1) or non-insulin-dependent (Type 2) diabetes who were observed on randomly selected days in 178 diabetes centres in Italy. Erectile dysfunction was defined as a failure to achieve and maintain an erection sufficient for satisfactory sexual performance. RESULTS: The study population consisted of 1383 Type 1 and 8373 Type 2 men. The prevalence of ED increased with age for both groups. After taking into account the effect of age Type 2 men (37/100 men) tend to report ED less frequently than Type 1 men (51/100 men). A significant positive relationship was reported between ED and poor metabolic control and smoking for both Type 1 and Type 2 men, whereas high body mass index (BMI) increased only the risk of ED in Type 1 cases. CONCLUSIONS: The study offers a quantitative estimate of the prevalence of ED and its main risk factors in Type 1 and Type 2 diabetic subgroups.
BACKGROUND: The potential therapeutic benefits of CD3 monoclonal antibodies, such as OKT3, have been limited by their immunogenicity and their propensity to activate a severe cytokine release syndrome. This has constrained the clinical use of OKT3 to the treatment of acute rejection episodes of organ allografts. METHODS: We have humanized a rat CD3 antibody and created a single amino acid substitution in position 297 of the IgG1 heavy chain to prevent glycosylation and, consequently, binding of the therapeutic antibody to Fc receptors and to complement. This antibody has been given as first line antirejection therapy in nine kidney transplant recipients with biopsy-proven acute rejection episodes. RESULTS: None of the patients demonstrated any antiglobulin response nor any significant cytokine release syndrome. Seven of the nine showed evidence of resolution of their rejection, although some patients experienced re-rejection. CONCLUSIONS: These findings suggest that CD3 antibodies can be engineered to lose their toxicity while retaining their potency as immunosuppressants. Nonactivating humanized CD3 monoclonal antibodies now merit further investigation in the management of transplant patients and in therapy of autoimmune diseases.
BACKGROUND: The first administration of CD3 monoclonal antibodies, such as anti-human CD3 (OKT3), induces a massive release of several cytokines, including tumor necrosis factor alpha (TNF-alpha), interferon (IFN)-gamma, interleukin (IL)-2, IL-3, IL-6, and granulocyte-macrophage colony-stimulating factor. METHODS: Cytokine levels in patient's sera were measured by specific ELISA. In vitro cultures were performed using OKT3-stimulated peripheral blood mononuclear cells and/or whole blood from patients and normal controls. RESULTS: Here we describe that OKT3 administration to human renal allograft recipients also leads to a significant release of IL-10. Contrasting with most OKT3-induced cytokines, such as TNF-alpha whose release is transient, IL-10 levels show a more progressive increase, they peak only by 4-8 hr after the first OKT3 injection and persist longer. Thus, significant IL-10 levels are still detectable at the time of the second and the third OKT3 injection. Administration of corticosteroids, 1 hr before the first OKT3 injection, significantly reduced both TNF-alpha and IL-10 release. Experiments were performed to evaluate the source(s) of IL-10 and its (their) influence on the initial T-cell activation. When stimulated in culture with soluble OKT3, the production of IL-10 was dependent on the cooperation between T lymphocytes and monocytes. It is important that, as assessed through the use of a specific neutralizing antibody, the endogenous IL-10 produced in the co-culture system exerted a negative feed-back on the release of the other pro-inflammatory CD3-induced cytokines, which was reproducible. CONCLUSION: These results are supportive of a major role of IL-10 in the down-modulation of the OKT3-triggered T-cell activation cascade.
Explore the source record for details and available documents.
To understand the role of NF-kappa B complexes in T cell development and activation, we have generated transgenic mice in which RelA and c-Rel complexes were selectively inhibited in the T-lineage cells by specific expression of a trans-dominant form of I kappa B alpha. Transgene expression did not affect the thymic development, but led to lowered numbers of splenic T cells and to a dramatic decrease in the ex vivo proliferative response of splenic T lymphocytes. Analysis of IL-2 and IL-2R alpha expression demonstrated that the perturbation of the proliferation response was not attributable to an abnormal expression of these genes. In contrast, expression of IL-4, IL-10, and IFN-gamma was strongly inhibited in the transgenic T cells. The proliferative deficiency of the transgenic T cells was associated with an increased apoptosis. These results point out the involvement of NF-kappa B/Rel family proteins in growth signaling pathways by either regulating proteins involved in the IL-2 signaling or by functionally interfering with the cell cycle progression.
Explore the source record for details and available documents.
A hospital-based case-control study was conducted in the Heilongjiang Province of northeast China between May 1993 and May 1995. A total of 129 histologically confirmed brain cancer cases (73 gliomas and 56 meningiomas) and 258 matched controls were interviewed in 6 major hospitals to examine the influence of dietary factors in developing brain cancer. Information was obtained about frequency of consumption of 57 food items. Odds ratios (ORs) were obtained from conditional logistic regression, including allowance for socio-demographic factors, alcohol, tobacco and total energy intake. Consumption of fresh vegetables (OR = 0.29 for the highest quartile compared with the lowest one), and specifically of Chinese cabbage and onion, fruit (OR = 0.15), fresh fish (OR = 0.38) and poultry (OR = 0.16) was inversely related to the risk of developing brain cancer. A protective effect was also seen for vitamin E intake, calcium and, although non-significantly, beta-carotene and vitamin C. Risk of brain cancer increased with consumption of salted vegetables (OR = 2.54) and salted fish.
Explore the source record for details and available documents.
OBJECTIVE: To analyze the relation between selected dietary indicators and the risk of uterine myomas. METHODS: We used data from a case-control study on risk factors for uterine myomas conducted in Italy between 1986 and 1997. Cases included 843 women with uterine myomas whose clinical diagnoses dated back no more than 2 years. Controls were 1557 women younger than age 55 who had not had hysterectomies and were admitted for acute nongynecologic, nonhormonal, nonneoplastic conditions. RESULTS: Women with uterine myomas reported more frequent consumption of beef, other red meat, and ham and less frequent consumption of green vegetables, fruit, and fish. The multivariate odds ratios in the upper tertile were 1.7 for beef and other red meat (95% confidence interval [CI] 1.4, 2.2), 1.3 for ham (95% CI 1.0, 1.6), 0.5 for green vegetables (95% CI 0.4, 0.6), and 0.8 for fruit consumption (95% CI 0.6, 1.0). CONCLUSION: Myoma is associated with beef and ham consumption, whereas high intake of green vegetables seems to have a protective effect.
Explore the source record for details and available documents.
OBJECTIVE: We conducted a case-control study to analyze risk factors for urogenital prolapse requiring surgery. METHODS: Cases were 108 women with a diagnosis of II or III degree uterovaginal prolapse and/or third degree cystocele. Controls were 100 women admitted to the same hospitals as the cases, for acute, non-gynecological, non-neoplastic conditions. RESULTS: Occupation showed an association with urogenital prolapse: in comparison with professional/managerial women, housewives had an odds ratios (OR) of urogenital prolapse of 3.1 (95% confidence interval (CI), 1.6-8.8). Compared with nulliparae, parous women tended to have a higher risk of genital prolapse (OR 2.6, 95% CI 0.9-7.8). In comparison with women reporting no vaginal delivery, the ORs were 3.0 for women reporting one vaginal delivery (95% CI 1.0-9.5), and 4.5 (95% CI 1.6-13.1) for women with two or more vaginal deliveries. Forceps delivery and birthweight were not associated with risk of prolapse after taking into account the effect of number of vaginal deliveries. The risk of urogenital prolapse was higher in women with mother or sisters reporting the condition: the ORs were, respectively, 3.2 (95% CI 1.1-7.6) and 2.4 (95% CI 1.0-5.6) in comparison with women whose mother or sisters reported no prolapse. CONCLUSIONS: Our data support the clinical suggestion that parous women are at a higher risk of prolapse and the risk increases with number of vaginal deliveries. First-degree family history of prolapse seems to increase the risk of prolapse.
OBJECTIVE: The relations between oral contraceptives (OC), hormone replacement therapy (HRT) for menopause, and other female hormone use and thyroid cancer risk was analyzed using the original data from 13 studies from North America, Asia and Europe. METHODS: Based on 2,132 cases and 3,301 controls, odds ratios (OR) and the corresponding 95% confidence intervals (CI) were obtained by conditional regression models, conditioning on study and age at diagnosis, and adjusting for age, radiation exposure and parity. RESULTS: Overall, 808 (38%) cases versus 1,290 (39%) controls had ever used OCs, corresponding to an OR of 1.2 (95% CI 1.0 to 1.4). There was no relation with duration of use, age at first use, or use before first birth. The OR was significantly increased for current OC users (OR = 1.5, 95% 1.0 to 2.1), but declined with increasing time since stopping (OR = 1.1 for > 10 years since stopping). The association was stronger for papillary cancers (OR = 1.6 for current users) than for other histologic types. No significant heterogeneity was observed across studies or geographic areas. Eight studies had data on HRT, for a total of 1,305 cases and 2,300 controls: 110 (8%) cases and 205 (9%) controls reported ever using HRT (OR = 0.8; 95% CI 0.6 to 1.1). The ORs were 1.6 (95% to 0.9 to 2.9) for use of fertility drugs, and 1.5 (95% CI 1.1 to 2.1) for lactation suppression treatment. CONCLUSIONS: The studies considered in these analyses include most of the epidemiological data on the role of exogenous hormone use in the etiology of thyroid cancer, and they provide reassuring evidence on the absence of an association of practical relevance. The moderate excess risk in current OC users, if not due to increased surveillance for thyroid masses among OC users, is similar to that described for breast cancer, and would imply a role of female hormones on thyroid cancer promotion. There was no indication of increased thyroid cancer risk 10 or more years after discontinuing OC use.
BACKGROUND: Although several studies have investigated the relation between fish consumption and the risk of cardiovascular diseases, less attention has been paid to the relation between fish consumption and cancer risk. OBJECTIVE: The relation between frequency of consumption of fish and risk of selected neoplasms was analyzed by using data from an integrated series of case-control studies conducted in northern Italy between 1983 and 1996. DESIGN: The overall data set included the following incident, histologically confirmed neoplasms: oral cavity and pharynx (n = 181), esophagus (n = 316), stomach (n = 745), colon (n = 828), rectum (n = 498), liver (n = 428), gallbladder (n = 60), pancreas (n = 362), larynx (n = 242), breast (n = 3412), endometrium (n = 750), ovary (n = 971), prostate (n = 127), bladder (n = 431), kidney (n = 190), thyroid (n = 208), Hodgkin disease (n = 80), non-Hodgkin lymphomas (n = 200), and multiple myelomas (n = 120). Control subjects were 7990 patients admitted for acute, nonneoplastic conditions unrelated to long-term modifications of diet. Odds ratios (ORs) were computed for subsequent levels of fish consumption compared with no or occasional consumption (<1 serving/wk) by using multiple logistic regression, including terms for several covariates. RESULTS: There was a consistent pattern of protection against the risk of digestive tract cancers with fish consumption: oral cavity and pharynx, OR = 0.5 for the highest compared with the lowest level of consumption; esophagus, OR = 0.6; stomach, OR = 0.7; colon, OR = 0.6; rectum, OR = 0.5; and pancreas, OR = 0.7. There were inverse trends in risk of larynx (OR = 0.7), endometrial (OR = 0.8), and ovarian (OR = 0.7) cancers and multiple myeloma (OR = 0.5). No pattern of cancer risk in relation to fish consumption was observed for cancers of the liver, gallbladder, breast, bladder, kidney, or thyroid or for lymphomas. CONCLUSION: This study suggests that the consumption of even relatively small amounts of fish is a favorable indicator of the risk of several cancers, especially of the digestive tract.
BACKGROUND: Although consumption of whole-grain foods seems to reduce the risk of several types of neoplasms, the potential influence of a diet rich in starches and refined grains is less clear. OBJECTIVE: We studied the relation between the frequency of consumption of refined cereals (bread, pasta, or rice) and the risk of selected neoplasms. DESIGN: This was an integrated series of case-control studies conducted in northern Italy between 1983 and 1993. The subjects were patients admitted to the major teaching and general hospitals in Milan and Pordenone with incident, histologically confirmed cancers: 343 with cancer of the oral cavity and pharynx, 94 with cancer of the esophagus, 146 with cancer of the larynx, 745 with cancer of the stomach, 955 with cancer of the colon, 625 with cancer of the rectum, and 428 with cancer of the thyroid. The control subjects were 3526 patients admitted to the same network of hospitals for acute nonneoplastic conditions unrelated to long-term modification of diet. Odds ratios (ORs) for consecutive tertiles of refined-cereal consumption were computed after allowance for sociodemographic variables, education, smoking status, alcohol consumption, body mass index, and consumption of fruit, vegetables, and whole-grain foods. RESULTS: The ORs for the highest tertile of refined-cereal intake were 1.6 for cancer of the oral cavity, pharynx, esophagus, or larynx; 1.5 for stomach cancer; 1.5 for colon cancer; 1.3 for cancer of the rectum; and 2.0 for thyroid cancer. The trends in risk were significant for all neoplasms considered. CONCLUSION: Consumption of refined cereals was associated with an increased risk of cancers of the large bowel, the stomach, and other selected digestive and nondigestive sites.
The relation between hypertension and the risk of selected hormone-related neoplasms in women was investigated in a network of case-control studies conducted in Italy during 1983-1996. Cases were women younger than 75 years with histologically confirmed cancer of the breast (n=3406), endometrium (n=745), ovary (n=970), and thyroid (n=145). Controls were 3054 women admitted in the same geographic area for acute, nonneoplastic, non-hormone-related diseases. Odds ratios (ORs) of treated hypertension were computed after allowance for sociodemographic factors, smoking habits, alcohol consumption, parity, menopausal status, and body mass index (BMI) by means of unconditional logistic regression. The ORs were 1.2 (95% CI, 1.1 to 1.4) for breast cancer and 1.6 (95% CI, 1.3 to 1.9) for endometrial cancer, and the elevated ORs persisted after >/=5 years since diagnosis of hypertension. No significant association was observed for ovarian and thyroid cancer. For breast cancer, the association was apparently stronger at age 55 years or over and consequently after menopause. No appreciable effect modification was evident for endometrial cancer. Allowance for BMI did not explain the association of postmenopausal breast cancer and endometrial cancer with hypertension. The OR of postmenopausal breast cancer was 1.5 (95% CI, 1.1 to 2.0) in hypertensive women with BMI >/=30 kg/m(2) compared with normotensive women with BMI <25 kg/m(2). The corresponding figure for all endometrial cancers was 4.9 (95% CI, 3. 4 to 6.9). Even in the absence of a clear understanding of biological mechanisms, the definition of a role of hypertension on female hormone-related cancers can have relevant implications on individual risk assessment.