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Biomedical subjects

S Uzan

Publications and source records attributed to S Uzan.

At least 73 records · Page 4Linked to original sources
PubMed2000

Deep vein thrombosis during enoxaparin prophylactic treatment in a young pregnant woman homozygous for factor V Leiden and heterozygous for the G127-->a mutation in the thrombomodulin gene.

Variability of thrombotic disease among individuals homozygous for factor V Leiden has been described. It has been shown that some thrombotic patients carry an additional genetic risk factor such as protein C, protein S, antithrombin deficiency or the G20210A mutation on the prothrombin gene. The occurrence of a deep vein thrombosis during enoxaparin prophylactic treatment in a pregnant woman homozygous for factor V Leiden, without other known prothrombotic genetic factors, led us to investigate her thrombomodulin gene. We found that the patient was heterozygous for the previously described G127-->A mutation, which results in an Ala25-->Thr substitution. Furthermore, for this patient, the allelic combination at the 1418 polymorphic site was C/T, which predicts an Ala455-->Val replacement. Although larger studies are required, this case report suggests that thrombomodulin gene mutations could be an additional genetic risk factor for thrombosis in carriers of the factor V Leiden mutation.

Adult↗
PubMed2000

Pregnancy, vascular tone, and maternal hemodynamics: a crucial adaptation.

UNLABELLED: The adaptation of vascular tone in early pregnancy precedes and probably triggers blood volume and cardiac output increase. Because the endothelium is known to regulate vascular smooth muscle action, the role of nitric oxide (NO) in the setting up of adequate uteroplacental and renal blood flow during normal pregnancy was investigated. The persistence of abnormally high uteroplacental resistance is a strong predisposing factor for intrauterine growth retardation and preeclampsia and can be screened by second trimester Doppler assessment of the uterine arteries. Current hypotheses suggested by experimental and clinical data concerning preeclampsia confirm the crucial role played by the endothelium and vascular tone adaptation. The analysis of these data leads to consider apart early-onset preeclampsia affecting pregnancies with growth retarded fetuses and associated with high vascular resistance. Lastly, NO donors seem to significantly decrease the impedance in the uteroplacental circulation and to improve fetoplacental hemodynamics assessed by Doppler measurements, and their therapeutic use in some forms of preeclampsia might be promising. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians LEARNING OBJECTIVES: After completion of this article, the reader will be able to summarize the events that regulate vascular tone in pregnancy, specifically the role of nitric oxide and other vasoactive prostaglandins in the regulation of vascular tone and to describe the various hypotheses concerning the mechanism and the mediators responsible for initiating endothelial damage in the various disorders of vascular tone in pregnancy.

Adult↗
PubMed2000

[Therapeutic management of ovarian dystrophy and insufficiency in abortion disorders: recent data].

Many reports suggested that the high rate of miscarriage in women with polycystic ovaries may be due to increased urine and/or plasma LH concentration. In fact, with the exception of pulsatile GnRH, any treatment likely to increase the plasma LH level results in unchanged or rather low miscarriage rates. Conversely, a reduction in this rate by GnRH agonists is not conclusive. Excess weight may also increase the risk of miscarriage. In women with incipient ovarian failure, the miscarriage rate is mainly linked to age. No stimulation has been found to be effective in these patients. There is a need for more extensive evaluation in GnRH analog microdoses, recombinant FSH and GnRH antagonists. Oocyte donations from younger women are difficult to obtain because of the lack of donors in France.

Abortion, Spontaneous↗
PubMed2000

Ursodeoxycholic acid in intrahepatic cholestasis of pregnancy. A retrospective study of 19 cases.

OBJECTIVE: We studied the clinical and biological effects and safety of ursodeoxycholic acid in patients with intrahepatic cholestasis of pregnancy (ICP). METHODS: All cases of ICP treated with ursodeoxycholic acid in our department from January 1st, 1991 to May 31st, 1997 were reviewed. RESULTS: Forty-three patients had ICP, of whom 19 received ursodeoxycholic acid. The first symptoms appeared after a mean of 29.7 weeks of pregnancy (WP). Treatment was started after a mean of 32 WP, and lasted a mean of 28.5 days. Fourteen patients showed a clinical improvement on UDCA, and 11 showed a biological improvement. Two had a biological deterioration with increased liver enzyme concentrations. CONCLUSIONS: Ursodeoxycholic acid appears to be an effective treatment for ICP, but further studies are needed to confirm its safety in pregnancy.

Adult↗
PubMed1999

[Risk factors in pre-eclampsia].

PATIENT-RELATED FACTORS: Multiparous patients with a past history of severe pre-eclampsia are a high risk population which should be identified early in pregnancy. Selection on this criterion alone is however insufficient for large scale screening and prevention because most of the susceptible women are nulliparous. Search for a particular familial or personal history of vascular disorders can be helpful. The usefulness of blood pressure measurements during the second trimester has not been proven. MARKERS: There is a significant association between pre-eclampsia and a large number of biological markers. No one assay can however fulfill the requirements for effective early screening because sensitivity is too low or the rate of false positives is too high, or because the examination is too invasive or costly. DOPPLER ANOMALIES: Doppler exploration of the uterine arteries at 20 to 24 weeks gestation offers satisfactory sensitivity and specificity but the positive predictive value is low. Persistence of a bilateral notch beyond 24 weeks considerably limits the number of false positives. More than half of the patients with this anomaly will develop hypertension during pregnancy. While no one marker fulfills all the prerequisites for effective screening, a combination of several tests may be useful. hCG assay during the second trimester in association with Doppler exploration of the uterine arteries appears to be a promising combination. PREVENTION: Starting with these markers or risk factors, the goal is to develop a prevention scheme using low-dose aspirin, the only evidence-based preventive treatment to date. Further trials are required to test simultaneously the predictive value and impact (versus placebo) of proposed strategies.

Aspirin↗
PubMed1999

Local recurrences and distant metastases after breast-conserving surgery and radiation therapy for early breast cancer.

PURPOSE: To identify predicting factors for local failure and increased risk of distant metastases by statistical analysis of the data after breast-conserving treatment for early breast cancer. METHODS AND MATERIALS: Between January 1976 and December 1993, 528 patients with nonmetastatic T1 (tumors < or = 1 cm [n = 197], >1 cm [n = 220]) or T2 (tumors < or = 3 cm [n = 111]) carcinoma of the breast underwent wide excision (n = 435) or quadrantectomy (n = 93) with axillary dissection (negative nodal status [n-]: 396; 1-3 involved nodes: 100; >3 involved nodes: 32). Radiotherapy consisted of 45 Gy to the entire breast via tangential fields. Patients with positive axillary lymph nodes received 45 Gy to the axillary and supraclavicular area. Patients with positive axillary nodes and/or inner or central tumor locations received 50 Gy to the internal mammary lymph node area. A boost dose was delivered to the primary site by iridium 192 Implant in 298 patients (mean total dose: 15.2+/-0.07 Gy, range: 15-25 Gy) or by electrons in 225 patients (mean total dose: 14.8+/-0.09 Gy, range: 5-20 Gy). The mean age was 52.5+/-0.5 years (range: 26-86 years) and 267 patient were postmenopausal. Histologic types were as follows: 463 infiltrating ductal carcinomas, 39 infiltrating lobular carcinomas, and 26 other histotypes. Grade distribution according to the Scarff, Bloom, and Richardson (SBR) classification was as follows: 149 grade 1, 271 grade 2, 73 grade 3, and 35 nonclassified. The mean tumor size was 1.6+/-0.3 cm (range: 0.3-3 cm). The intraductal component of the primary tumor was extensive (EIC = IC > or = 25%) in 39 patients. Tumors were microscopically bifocal in 33 cases. Margins were assessed in the majority of cases by inking of the resection margins and were classified as positive in 13 cases, close (< or = 2 mm) in 21, negative (>2 mm tumor-free margin) in 417, and indeterminate in 77. Peritumoral vascular invasion was observed in 40 patients. Tamoxifen was administered for at least 2 years in 176 patients. At least six cycles of adjuvant systemic chemotherapy were administered in 116 patients. The mean follow-up period from the beginning of the treatment was 84.5+/-1.7 months. RESULTS: First events included 44 isolated local recurrences, 8 isolated axillary node recurrences, 44 isolated distant metastases, 1 local recurrence with synchronous axillary node recurrence, 7 local recurrences with synchronous metastases, and 2 local recurrences with synchronous axillary node recurrences and distant metastases. Of 39 pathologically evaluable local recurrences, 33 were classified as true local recurrences and 6 as ipsilateral new primary carcinomas. Seventy patients died (47 of breast carcinoma, 4 of other neoplastic diseases, 10 of other diseases and 9 of unknown causes). The 5- and 10-year rates were, respectively: specific survival 93% and 86%, disease-free survival 85% and 75%, distant metastasis 8.5% and 14%, and local recurrence 7% and 14%. Mean intervals from the beginning of treatment for local recurrence or distant metastases were, respectively, 60+/-6 months (median: 47 months, range: 6-217 months) and 49.5+/-5.4 months (median: 33 months, range: 6-217 months). After local recurrence, salvage mastectomy was performed in 46 patients (85%) and systemic hormonal therapy and/or chemotherapy was administered to 43 patients. The 5-year specific survival rate after treatment for local recurrence was 78+/-8.2%. Multivariate analysis (multivariate generalization of the proportional hazards model) showed that the probability of local control was decreased by the following four independent factors: young age (< or = 40 yr vs. >40 yr; relative risk [RR]: 3.15, 95% confidence interval [CI]: 1.7-5.8, p = 0.0002), premenopausal status (pre vs. post; RR: 2.9, 95% CI: 1.4-6, p = 0.0048), bifocality (uni- vs. bifocal; RR: 2.7, 95% CI: 2.6-2.8,p = 0.018), and extensive intraductal component (IC <25% vs. IC > or = 25%; RR: 2.6, 95% CI: 13-5.2, p = 0

Adult↗
PubMed1999

Effect of aspirin in pregnant women is dependent on increase in bleeding time.

OBJECTIVES: Randomized trials with low-dose aspirin to prevent preeclampsia and intrauterine growth restriction have yielded conflicting results. In particular, 3 recent large trials were not conclusive. Study designs, however, varied greatly regarding selection of patients, dose of aspirin, and timing of treatment, all of which can be determinants of the results. Retrospectively analyzing the conditions associated with failure or success of aspirin may therefore help to draw up new hypotheses and prepare for more specific randomized trials. STUDY DESIGN: We studied a historical cohort of 187 pregnant women who were considered at high risk for preeclampsia, intrauterine growth restriction, or both and were therefore treated with low-dose aspirin between 1989 and 1994. Various epidemiologic, clinical, and laboratory data were extracted from the files. Univariate and multivariate analyses were performed to search for independent parameters associated with the outcome of pregnancy. RESULTS: Age, parity, weight, height, and race had no influence on the outcome. The success rate was higher when treatment was given because of previous poor pregnancy outcomes than when it was given for other indications, and the patients with successful therapy had started aspirin earlier than had those with therapy failure (17.7 vs 20.0 weeks' gestation, P =.04). After multivariate analysis an increase in Ivy bleeding time after 10 days of treatment by >2 minutes was an independent predictor of a better outcome (odds ratio 0.22, 95% confidence interval 0.09-0.51). Borderline statistical significance was observed for aspirin initiation before 17 weeks' gestation (odds ratio 0.44, 95% confidence interval 0.18-1. 08). Abnormal uterine artery Doppler velocimetric scan at 20-24 weeks' gestation (odds ratio 3.31, 95% confidence interval 1.41-7.7), abnormal umbilical artery Doppler velocimetric scan after 26 weeks' gestation (odds ratio 37.6, 95% confidence interval 3.96-357), and use of antihypertensive therapy (odds ratio 6.06, 95% confidence interval 2.45-15) were independent predictors of poor outcome. CONCLUSIONS: Efficacy of aspirin seems optimal when bleeding time increases >/=2 minutes with treatment, indicating a more powerful antiplatelet effect. This suggests that the dose of aspirin should be adjusted according to a biologic marker of the antiplatelet effect. A prospective trial is warranted to test this hypothesis.

Adult↗
PubMed1999

Detection of hepatitis C virus RNA (HCV RNA) in amniotic fluid: a prospective study.

BACKGROUND/AIMS: Mother-to-infant transmission of hepatitis C virus (HCV) has been reported, but the transmission route is unknown. The aim of our study was to detect HCV RNA in amniotic fluid of pregnant women seropositive for HCV. METHODS: Twenty-two HCV seropositive women were included in the study (median age: 39 years). An amniocentesis was performed in all patients during the 4th month of pregnancy. Sixteen women also tested positive for HCV RNA in serum. The range of HCV RNA titers was 0.3 to 15.1x10(6) Eq/ml (Quantiplex HCV RNA 2.0 Assay, Chiron Diagnostics). Of these 16 viremic patients, four had an anterior placenta, ten had a posterior placenta and the position of the placenta was not determined in two cases. PCR (Amplicor HCV, Roche Diagnostics) was used to detect HCV RNA in the amniotic fluid. We also studied 11 HCV seronegative women as a control group. RESULTS: In the viremic group (n = 16), HCV RNA was detected once in amniotic fluid. The positive specimen was collected from a patient with an HCV RNA serum value equal to 1.1x10(6) Eq/ml. The placenta was in an anterior position. A PCR inhibitor was detected in one case. No HCV RNA was detected in the amniotic fluid of six seropositive non-viremic patients, nor in the control group. Serum HCV RNA was negative in the ten children tested. The woman whose amniotic fluid contained HCV RNA was the mother of one of them. CONCLUSIONS: HCV RNA detection in amniotic fluid is rarely positive. The anterior position of the placenta in the only positive detection cannot rule out contamination of the amniotic fluid during the transplacental amniocentesis.

Adult↗
PubMed1999

[Sickle cell anemia and pregnancy. Complications and management].

An increasing number of sickle cell disease patients are deciding to bear children. The high risk of fetal and maternal complications in pregnant sickle cell disease patients mandates multidisciplinary management. Risks include spontaneous abortion, vasculorenal syndrome, fetal growth retardation, and fetal death in utero. The rates of cesarean section, maternofetal infection, and maternal death are higher than in the population at large. The diagnosis should be made prior to conception or during early pregnancy. Frequent visits with the obstetrician, hematologist, and anesthesiologist/intensivist are mandatory. Exchange transfusion or blood transfusion may be indicated in patients with a history of serious obstetrical or hematologic complications. Risks are highest in late pregnancy, during delivery, and in the postpartal period. However, the entire pregnancy is a high-risk period that warrants close monitoring.

Anemia, Sickle Cell↗
PubMed1999

Immunostaining of vascular, perivascular cells and stromal components in human placental villi.

Fetal placental vessels develop and adapt in order to supply the fetus with nutrients. Immunostaining by antibodies against blood clotting factors, cell-cell and cell-matrix adhesion molecules, intermediate and contractile filaments, matrix components and enzymes give an overall view useful in assessing cell differentiation in placental villi. Endothelial cells stained positively for thrombomodulin, von Willebrand factor, CD34, CD31, cadherin-5, phalloidin and alpha 3-integrin. Trophoblastic cells were positive for cytokeratin, alpha 5 and alpha V integrins, L-prolyl hydroxylase and phalloidin. Myocytes from the media of stem villi exhibited positive vimentin, desmin, alpha-sm-actin and sm-myosin reactions but were CD26 negative. Myofibroblasts were vimentin, desmin, CD26, alpha-sm-actin and sm-myosin positive. Perivascular cells of intermediate and terminal villi were alpha-sm-actin, sm-myosin and anti-high molecular weight melanoma associated antigen (HMWMAA) positive. Trophoblastic and endothelial basement membranes were collagen IV positive. The most specific endothelial markers were cadherin-5, observed only at paracellular clefts, and von Willebrand factor. For perivascular cells, alpha-sm-actin, sm-myosin and HMWMAA provided a specific labeling. Differences in labeling intensity were noted along the cross section of the villous tree (vimentin, desmin, actin, myosin inward gradient). A continuity in the contractile function along the vessel length was indicated by alpha-sm-actin and sm-myosin positive cells, contrasting with the decreased von Willebrand reaction intensity. These data are discussed in relation to cell function and compared to cell culture results.

Actins↗
PubMed1999

[Inflammatory and/or locally advanced breast cancers. Difficulty evaluating the response to initial chemotherapy].

At the Tenon Hospital (Paris), 48 inflammatory or locally advanced breast cancers were treated by neoadjuvant chemotherapy (three different protocols), followed by surgery (mastectomy or tumorectomy and axillary dissection). The histological data of the specimens are analyzed with regard to the clinical and radiologic evolution. Twenty complete clinical responses (41%), 22 partial clinical responses (45%), and no response in six cases (14%) were observed. Histology demonstrated residual tumors in 42 cases (87.5%), even in the case of complete clinical response (14 cases), without notable change of the grade (SBR). Lymph node clearance demonstrated positive nodes in 38 cases (79%). Despite its great agreement with clinical examination, mammography does not predict the existence of histological residual tumors after initial chemotherapy. Chemotherapy allowed local treatment, but can rarely sterilize the tumor completely.

Adult↗