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Biomedical subjects

L Chatenoud

Publications and source records attributed to L Chatenoud.

At least 91 records · Page 5Linked to original sources

A pilot trial of recombinant human interleukin-10 in kidney transplant recipients receiving OKT3 induction therapy.

BACKGROUND: We conducted a randomized, double-blind, placebo-controlled, rising single-dose study to investigate the effects of recombinant human (rh) interleukin (IL) 10 in renal transplant patients who received OKT3 as induction therapy. METHODS: Patients received 0.1 (n=6), 1 (n=6), or 10 microg/kg (n=3) rhIL-10 or placebo (n=6) intravenously 30 min before the first injection of 5 mg of OKT3. We monitored IL-10 serum levels, the effect of rhIL-10 on OKT3-induced cytokine production, clinical toxicity, and the incidence of immunization against OKT3. RESULTS: Serum IL-10 levels in the three experimental groups reached 0.8+/-0.2, 7.9+/-1.3, and 118.6+/-7.3 ng/ml (mean+/-SEM), respectively, 30 min after rhIL-10 injection. Peak plasma levels of tumor necrosis factor-alpha (TNF-alpha) were reduced from 2953+/-1599 pg/ml in patients injected with OKT3 and placebo to 447+/-155, 703+/-246, and 459+/-246 pg/ml in patients injected with 0.1, 1, and 10 microg/kg rhIL-10, respectively. Values for 24-hr TNF-alpha area under the curve decreased from 8988+/-3551 pg x hr/ml in control patients to 2284+/-494, 3950+/-955, and 2420+/-931 pg x hr/ml for the 0.1, 1, and 10 microg/kg rhIL-10 dose groups, respectively (P=0.045). There was also a trend toward reduced plasma levels of IL-2, IL-8, and interferon-gamma in rhIL-10-pretreated patients. Although none of the patients who received placebo or 0.1 or 1 microg/kg rhIL-10 developed an IgM antibody response directed against OKT3 during the first 10 days, this occurred in all three patients who received the highest rhIL-10 dose. In two of these patients, neutralization of OKT3 was associated with a reversible acute rejection episode. CONCLUSIONS: Pretreatment with doses of up to 1 microg/kg rhIL-10 is safe and reduces the release of TNF-alpha induced by OKT3. However, higher doses might promote early sensitization to OKT3.

Adult↗

Case-control study of oestrogen replacement therapy and risk of cervical cancer.

OBJECTIVE: To examine the relation between use of oestrogen replacement therapy and risk of cervical cancer. DESIGN: Case-control study. SETTING: Northern Italy. SUBJECTS: 645 women aged 40-75 years with cervical cancer admitted between 1981 and 1993 to university and general hospitals. The control group consisted of 749 women aged 40-75 years admitted to the same hospitals with acute conditions judged to be unrelated to any of the known or suspected risk factors for cervical cancer. MAIN OUTCOME MEASURES: Use of oestrogen replacement therapy and risk of cervical cancer. RESULTS: 40 cases versus 86 controls had ever used oestrogens, and the corresponding multivariate odds ratio was 0.5 (95% confidence interval 0.3 to 0.8). The odds ratios of cervical cancer decreased with duration of use, being 0.6 (0.4 to 1.1) for less than 12 months' use and 0.5 (0.2 to 1.0) for use for 12 months or more compared with never users. The protection tended to be somewhat stronger for women reporting first oestrogen use before age 50. The odds ratio was 0.9 (0.5 to 1.7) for women who had taken oestrogens within the past 10 years and 0.4 (0.2 to 0.7) for those who had taken them 10 or more years ago. CONCLUSION: These findings suggest that exogenous oestrogens do not increase the risk of cervical cancer and may decrease the risk.

Adenocarcinoma↗

CD3 antibody-induced dominant self tolerance in overtly diabetic NOD mice.

Low doses of the CD3 mAb 145 2C11 restored self tolerance to beta cell Ags in adult overtly diabetic NOD mice. Within 2 to 4 wk after treatment, complete and permanent remission of diabetes was observed. Autoreactive T cells were not deleted in CD3 Ab-protected animals as evidenced first, by the persistence of peripheral insulitis and, second, by the capacity of spleen cells from CD3 Ab-treated mice to transfer diabetes to adult irradiated syngeneic recipients. Moreover, the conferred tolerance was reproducibly reversed by a single injection of cyclophosphamide. For 5 to 7 wk after treatment, IFN-gamma production by stimulated spleen cells was significantly decreased in treated animals. One unique feature was that the CD3 Ab-induced tolerance ensued only from treatment of overtly diabetic NOD mice. Durable protection was exclusively observed when treating mice with recent onset disease (14-20 wk old). At variance with this finding, treatment of 4- and 8-wk-old mice was without effect, and complete but transient protection followed the treatment of 12-wk-old NOD mice. The tolerogenic properties of 145 2C11 did not depend on its mitogenic capacity, since nonmitogenic F(ab')2 fragments also appeared potent at inducing durable remission in overtly diabetic NOD, although nonmitogenic CD3 F(ab')2 fragments could mediate T cell signaling, as evidenced by cytokine gene transcription (IL-2, IFN-gamma, IL-4, and IL-10) assessed by PCR on splenocytes from treated mice. A concomitant cyclosporine treatment abrogated the CD3 mAb-induced protection, further pointing to the crucial role of T cell signaling in the effect observed.

Adoptive Transfer↗

Exposure to video display terminals and risk of spontaneous abortion.

Clusters of spontaneous abortion among video display terminal (VDT) users in North America and Canada in the late 1970s aroused suspicion about the potential risk of an association between VDT. exposure and pregnancy outcome. This case-control study considered the association between VDT use and the risk of miscarriage. Cases were 508 women admitted for spontaneous abortion to the Clinica Luigi Mangiagalli and a network of obstetric departments in the Milan area. Controls were 1,148 women who gave birth at term to healthy infants on randomly selected days at the same hospitals where cases were identified. No association emerged between VDT exposure and spontaneous abortion, the estimated odds ratio being 1.0 (95% CI: 0.8-1.2). This evidence agrees with studies conducted in different countries by various authors.

Abortion, Spontaneous↗

Risk factors for adenomyosis.

In order to analyse risk factors for adenomyosis, 707 consecutive women who underwent hysterectomy between January 1993 and June 1994 at the Clinica Luigi Mangiagalli, Milan, Italy, were interviewed before surgery by trained physicians. Information on the presence of adenomyosis was obtained from pathologic records. Out of the 707 women, adenomyosis was identified in 150 subjects (21.2%). Women who smoked tended to be at decreased risk of the condition: in comparison with women who had never smoked, the risk for current smokers was 0.7 (0.3-1.3) and the risk decreased with number of cigarettes smoked per day, the odds ratios being 0.8 and 0.6 respectively in women reporting fewer than 10 and more than 10 cigarette smoked per day (chi2 trend 3.57, P = 0.06). The frequency of adenomyosis was higher in parous women: in comparison with nulliparae, the odds ratio of the disease were 1.8 [95% confidence interval (CI) 0.9-3.4] and 3.1 (95% CI 1.7-5.5) respectively in women reporting one and two or more births (chi2 trend 20.71, P < 0.01). Likewise, women reporting one or more spontaneous abortions had an odds ratio of 1.7 (95% CI 1.1-2.6) for adenomyosis, in comparison with those reporting no spontaneous abortion.

Abortion, Spontaneous↗

Determinants of risk of spontaneous abortions in the first trimester of pregnancy.

Several factors, such as socioeconomic status, obstetrical and menstrual history, and contraceptive methods, have been associated with risk of spontaneous abortion. We conducted a hospital case-control study to analyze risk factors for spontaneous abortion during the first trimester. Cases were 782 women admitted for spontaneous abortion. Controls included 1,543 women who gave birth at term in the same hospitals. Adjusted odds ratios (ORs) for spontaneous abortion were 0.9 and 0.6, respectively, for women reporting 7-11 and > or = 12 years of schooling, compared with women reporting < 7 years of education. A history of pelvic inflammatory disease increased the odds ratio fivefold [OR = 5.1; 95% confidence interval (CI) = 1.0-26.2]. The OR for spontaneous abortion was 1.7 (95% CI = 1.4-2.1) in women reporting previous spontaneous abortions.

Abortion, Spontaneous↗

Semen parameters and conception rates after intraperitoneal insemination.

OBJECTIVE: To analyze the reproductive outcome in infertile couples which underwent intraperitoneal insemination (IPI). METHODS: We analyzed a series of 216 couples who underwent IPI. Indications for treatment were unexplained infertility in 51 couples and male factor in 165. The 51 couples with unexplained infertility underwent a total of 71 cycles (20 couples underwent a second IPI cycle). The 165 couples with male factor underwent 243 cycles (165 first cycles and 78 second cycles). RESULTS: Out of the 314 cycles performed, a total of 41 clinical pregnancies were observed, with a corresponding conception rate of 13.1%. The values of conception rates for unexplained and male factor infertility were 21.1 (based on 15 pregnancies) and 10.7% (based on 26 pregnancies), respectively. Out of the 41 pregnant women, 26 gave birth to a child, thus the overall livebirth rate was 8.3% (12.7 and 7.0%, respectively, for unexplained infertility and male factor diagnostic subgroups). Considering the couples with unexplained infertility, the conception rates were 9.0, 30.8 and 20.0% for strata of < 5, 5-10 and > or = 10 millions of inseminated spermatozoa. The corresponding values were 6.8, 12.5 and 18.5%, respectively, in couples with male factor infertility (chi(2)1 trend p < 0.05). CONCLUSION: In conclusion, this series provides quantitative estimates of pregnancy rates after IPI in Italian couples with unexplained infertility or male infertility and suggested that the number of motile sperm inseminated is a determinant of pregnancy with this technique.

Female↗

The epidemiology of gestational trophoblastic disease.

Considerable progress has been made in the knowledge of the epidemiology of gestational trophoblastic disease (GTD) in the last few years. There are two main and widely known points related to this disease: its geographical distribution and the different frequency in the various classes of age. GTD is more frequent in South-East Asia, India and Africa, and is rare in European and North American populations. For example, in the United States, the frequency of GTD was 108 per 100,000 pregnancies in the 1970's. In Europe, particularly in Italy, frequencies are lower. In northern Italy, the frequency of hydatidiform mole, in the period 1979-1982, was equal to 62 per 100,000 pregnancies, but in Indonesia and in China, the reported rates were 993 and 667 per 100,000 pregnancies respectively. GTD disease is more frequent in the extreme classes of age (under 20 and over 40 years) and the risk may be more than 100 times greater over 50 years. Besides these risk factors, the possible role of both genetic (familiarity, blood groups) and environmental factors (diet, cigarette smoking, etc.) has been investigated on the onset of GTD. This paper reviews the epidemiologic knowledge on GTD.

Adolescent↗

The IgE humoral response in OKT3-treated patients. Incidence and fine specificity.

We recently described a case of anaphylaxis occurring at the time of retreatment with OKT3 of a renal allograft recipient in whom, for the first time, high anti-OKT3 IgE levels were documented. This led us to examine a large series of sera from 181 OKT3-treated patients to better define the frequency of IgE sensitization, its fine specificity (anti-isotypic and/or anti-idiotypic) and its relation to the appearance of IgG anti-OKT3 antibodies (Abs). Six patients out of the 181 assayed have developed anti-OKT3 IgE Abs as detected by ELISA. The earliest time of appearance of IgE anti-OKT3 Abs was 10 days after starting OKT3 (range, 10-25). The IgE response peaked by day 18 (range, 11-35) and had usually disappeared at 3 months after treatment. A more careful dissection of the fine specificity of the IgE response revealed that three of the four patients tested had developed an exclusive anti-idiotypic response. In the last patient, an anti-isotypic component was present since anti-OKT3 IgE Abs also reacted with control IgG2a, IgG2b, and IgG3 monoclonal antibodies. Importantly, anti-OKT3 IgE Abs were only detected in heavily sensitized patients also showing high titers of IgG specific Abs by ELISA (> or = 1/1000) as well as "blocking" anti-OKT3 antibodies, as assessed by immunofluorescence. We conclude that (1) exposure to OKT3 may lead to specific IgE sensitization that, however, only appears in about 38% of the patients; (2) IgE Abs mostly appear in patients also showing high levels of conventional IgG anti-OKT3 Abs including the presence of "blocking" anti-idiotypic Abs, and (3) IgE Abs may be directed to both idiotypic and isotypic determinants of the monoclonal antibody.

Animals↗

Attitudes and clinical practice of Italian gynecologists towards prophylactic oophorectomy during hysterectomy for benign conditions.

OBJECTIVES: To evaluate the attitudes of Italian gynecologists towards prophylactic oophorectomy in women who underwent hysterectomy for benign conditions. METHODS: A postal questionnaire was sent to 490 physicians in charge in 42 obstetric and gynecologic centres affiliated to the Association of Italian Obstetrics and Gynecologists. RESULTS: About 80% of gynecologists perform prophylactic oophorectomy for women aged more than 50, but this percentage decreases to 50% for patients aged 45-50. Most gynecologists avoid prophylactic oophorectomy in women aged less than 40. CONCLUSIONS: This study confirms the wide variability in attitudes of gynecologists towards prophylactic oophorectomy in women aged 40-50 who undergo hysterectomy for benign conditions.

Adult↗

Coffee and alcohol intake, smoking and risk of multiple pregnancy.

We analysed the relationship between coffee and alcohol intake, smoking and risk of multiple pregnancies using data from a case-control study on risk factors for multiple births conducted in Italy. Cases were 133 women who delivered multiple births not related to treatment for infertility (33 monozygotic and 100 dizygotic twins). Controls were 395 women admitted for normal delivery at the same clinic where cases had been identified. The odds ratios (OR) of multiple pregnancy were 1.5[95% confidence interval (CI) 0.8-2.8] and 2.0 (95% CI 1.0-3.7) for women drinking respectively one to two or three or more cups of coffee per day in comparison with non-coffee drinkers. Considering separately dizygotic and monozygotic pregnancies, the estimated OR were respectively for women drinking three or more cups of coffee, 1.7 and 3.1 for dizygotic and monozygotic pregnancies. The risk of multiple pregnancy tended to be higher in women drinking >or= 15 alcohol drinks per week: in comparison with tea-totallers the estimated OR for drink > or = 15 glasses per week were 2.3 and 2.6 respectively for dizygotic and monozygotic pregnancies. Heavy smokers (> or = 10 cigarettes per day) were at increased risk of multiple pregnancy: in comparison with never smokers, the estimated OR for multiple pregnancy was 1.6 (95% CI 0.9-2.7). Considering separately the two groups of multiple pregnancy, the OR of dizygotic and monozygotic pregnancy were 1.4 (95% CI 0.8-2.5) and 2.4 (95% CI 0.9-6.1) for women smoking > or = 10 cigarettes/day, but the trend in risk with number of cigarettes smoked per day and duration of the habit was not significant.

Adult↗

Risk factors for pregnancy-induced hypertension in women at high risk for the condition. Italian Study of Aspirin in Pregnancy Group.

To analyze determinants of the risk of pregnancy-induced hypertension (PIH) with or without proteinuria, we compared characteristics of women enrolled in the Italian Study of Aspirin in Pregnancy who developed PIH and those who did not. A total of 756 women were included in the present analysis; of these, 132 women (17%) developed PIH during the trial. The risk of developing PIH tended to increase with maternal age: in comparison with women age 20-25 years, the odds ratio (OR) estimates of risk ratio were 3.5 [95% confidence interval (CI) = 1.6-7.1] in women age 26-30 years and 4.2 (95% CI = 1.9-8.8) in those age > 30 years. There was little relation between development of PIH and education. PIH risk increased according to nonpregnant body mass index; in comparison with women with Quetelet's index (kg per m2) < 25, the OR estimates were 1.7 (95% CI = 1.1-2.7) and 2.1 (95% CI = 1.3-3.6), respectively, for women with a value for Quetelet's index of > 25-30 and > 30. Parous women were at decreased risk of PIH: in comparison with nulliparas, the ORs were 0.7 (95% CI = 0.4-1.0) and 0.5 (95% CI = 0.3-0.9), respectively, in women reporting 1 or > or = 2 births. There was no important relation between previous spontaneous or induced abortion and PIH risk.

Adult↗