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Biomedical subjects

Patrick Madelenat

Publications and source records attributed to Patrick Madelenat.

10 recordsLinked to original sources

Effects of a Gonadotropin-Releasing Hormone agonist and Follicle Stimulating Hormone on the incidence of apoptosis in human luteinized granulosa cells.

OBJECTIVE: Previous studies have shown the importance of apoptosis in follicular atresia occurring especially in granulosa cells (GC) and its relation to the outcome of in vitro fertilization (IVF). The aim of this study was to evaluate the effects of a Gonadotropin-Releasing Hormone agonist (GnRHa) and of Follicle-Stimulating Hormone (FSH) on the apoptosis rate of human luteinized GC. STUDY DESIGN: GC were isolated from follicular fluids of 15 women undergoing IVF cycles, cultured for 1 day and then treated for 1 day in serum-free medium with triptorelin at 100 or 1000pg/ml or with FSH at 100 or 500ng/ml. GC cultured without any hormone addition were used as controls. Treatment of cultured GC with triptorelin 100pg/ml and FSH 100ng/ml was performed five times each. GC were analysed by flow cytometry after propidium iodide staining to measure the percentage of apoptotic GC. Some triptorelin-treated GC were also examined by electron microscopy. RESULTS: Percentages of GC apoptosis were after hormone treatment respectively: FSH: 100ng/ml, 2.9+/-0.6%; 500ng/ml, 2.9%; triptorelin: 100pg/ml, 18.6+/-2.8%; 1000pg/ml, 86.5% versus 9.8+/-1.8% in GC controls (FSH 100ng/ml versus control; triptorelin 100pg/ml versus control: P<10(-6)). Electron microscopy confirmed apoptosis of GC incubated with triptorelin. CONCLUSIONS: This study demonstrated that FSH decreased apoptosis in human luteinized GC. In contrast, triptorelin was possibly implicated in a dose-dependent increase in the incidence of apoptotic GC. This last result suggests that clinical use of GnRHa should perhaps be reconsidered in the context of its apoptosis-inducing effect.

Adult↗

Safety of cryopreservation straws for human gametes or embryos: a study with human immunodeficiency virus-1 under cryopreservation conditions.

BACKGROUND: The possibility of assisted reproductive technology (ART) for couples carrying viruses, especially HIV-1, necessitates consideration of the safety of cryopreserving human gametes or embryos in liquid nitrogen tanks. Following our evaluation of the safety of three kinds of straws containing HIV-1 at 37 degrees C, we have now examined the HIV-1 imperviousness of the same straws under cryopreservation conditions. METHODS: Polyvinyl chloride (PVC), polyethylene terephthalate glycol (PETG) and high-security ionomeric resin (IR) straws (24 each) were tested. Each straw was filled with 100 microl of HIV-1-containing supernatant [reverse transcriptase (RT) activity: 15 000 c.p.m./50 microl]. Then PVC and PETG straws were sealed ultrasonically only at their free-end, and IR straws were thermosoldered at both ends. Each straw was put in a 15 ml Falcon tube which was capped and submerged in a liquid-nitrogen tank for 7 days. After bleach decontamination or not, the outside of each end of the straw was rinsed with RPMI medium (1 ml) before cryopreservation and after thawing. Viral RNA was extracted from the medium and then amplified by RT-polymerase chain reaction (PCR) followed by nested-PCR using HIV-1 protease-specific primers. RESULTS: HIV-1 RNA was detected in some PVC and PETG rinse media, probably resulting from splashing during ultrasonic sealing, but not in the rinse media of thermosoldered IR straws. CONCLUSION: Under cryopreservation conditions, IR straws would appear to be safe for HIV-1 storage in ART. For PVC and PETG straws, as highlighted in this study, the ultrasonic sealing could be the weak safety link.

Composite Resins↗

Hepatocyte growth factor and c-Met in cervical intraepithelial neoplasia: overexpression of proteins associated with oncogenic human papillomavirus and human immunodeficiency virus.

PURPOSE: High prevalence of squamous cervical intraepithelial neoplasia (CIN) linked to oncogenic human papillomavirus (HPV) exits in HIV-infected women. Hepatocyte growth factor (HGF) and its receptor, c-Met, promote cell proliferation and are involved in tumor progression. Nothing is yet known about their expression in low- and high-grade CIN. Therefore, the expression, localization, and behavior of HGF and c-Met in normal and dysplastic cervical epithelium were investigated. EXPERIMENTAL DESIGN: We studied normal cervical mucosa from 10 healthy women, and low- and high-grade cervical lesions, uninfected (condyloma acuminata) or infected with oncogenic HPVs, from 40 HIV-negative and 48 HIV-positive women, using in situ molecular techniques, immunocytochemistry and morphoquantitative methods. RESULTS: In 154 oncogenic HPV-infected CIN encountered in biopsy samples, the total number of epithelial cell layers increased significantly during lesion progression. This number was significantly higher in HIV-positive than in HIV-negative women for CIN1 and CIN2 (P < 0.025 to P < 0.01). In HIV-negative women, the number and percentage of HGF and c-Met immunostained cell layers, and the intensity of immunostaining were enhanced in oncogenic HPV-infected lesions as compared with normal mucosa and condyloma acuminata. The latter parameters were significantly higher in tissues of HIV-positive women (oncogenic HPV-infected CIN1 and CIN2, normal-appearing mucosa contiguous to CIN, condyloma acuminata) than in the corresponding tissues of HIV-negative women (P < 0.025 to P < 0.0001). CONCLUSIONS: Overexpression of HGF/c-Met complex strongly correlates with oncogenic HPV and HIV infection. This overexpressed complex may stimulate cell proliferation in condyloma acuminata and participate in tumor progression in oncogenic HPV-infected lesions.

Adolescent↗

[Diagnosis of ectopic pregnancy].

The knowledge of ectopic pregnancies risk factors (intra-uterine device; past history of pelvic inflammatory disease; history of tubal pathology and tubal surgery; positive chlamydiae serology; and smoking), the high sensitivity and specificity of radioimmunological assay of beta-HCG and the availability of high resolution sonography using vaginal probes had improved the routinely diagnosis of ectopic pregnancy. Today, diagnosis was made with beta-HCG and vaginal echography. Uterine vacuity, peritoneal liquid and latero-uterine masse represent the major ultrasound signs. However, diagnosis can be uncertain below discriminative zone of beta-HCG (< 1,500 to 2,000 UI/L). Other new diagnostic markers are also described, as progesterone, creatine kinase, VEGF and CA 125. The place of ponction of the Douglas, endouterine curettage, hysteroscopy and laparoscopy are also defined for diagnosis of ectopic pregnancy.

Algorithms↗

[Tibolone].

INDIRECT MECHANISM OF ACTION: Tibolone (OD 14) is the precursor of its active principles that are its metabolites: 3 alpha and 3 beta hydroxylated derivatives. In vivo, the latter behave like estrogens. Certain tissues (liver, endometrium) may metabolize the 3 beta ol derivative into the delta 4 isomer with progestagenic and androgenic activity. The metabolism of the product in other tissues such as the breast and brain is unknown. ACTIVITY: At the dose of 2.5 mg/day, the product expresses an estrogen activity equivalent to that observed with classical doses of estrogens in the brain, genito-urinary tract, vascular endothelium and bone. In the brain and muscle, it also has a slightly androgenic effect and in the breast an antiestrogenic effect. ON METABOLIC LEVEL: The product acts like a minor androgen (lowering triglycerides and HDL cholesterol without interfering in the cholesterol cell flow) and it stimulates fibrinolysis. ON CLINICAL LEVEL: Tibolone treats the symptoms of estrogen privation and protects against bone loss, without inducing bleeding or mastodynia. There is a lack of large epidemiological studies on prevention of fracture risks, cardiovascular effects and breast. Tolerance in the population studied was excellent (healthy population). However, tolerance remains to be assessed in particular sub-groups (populations at risk of certains pathologies).

Adult↗

Anal fissure and thrombosed external hemorrhoids before and after delivery.

PURPOSE: Thrombosed external hemorrhoids and anal fissures are common and are responsible for severe discomfort during childbirth. However, the real incidence of these lesions is unknown. The aim of our study was to evaluate their incidence and the risk factors for these lesions during childbirth. METHODS: A prospective study with proctologic examination during the last 3 months of pregnancy and after delivery (within 2 months) was performed in 165 consecutive pregnant females. RESULTS: Fifteen females (9.1 percent) with anal lesions (13 thrombosed external hemorrhoids and 2 anal fissures) were observed during pregnancy. Fifty-eight females (35.2 percent) with anal lesions (33 thrombosed external hemorrhoids and 25 anal fissures) were observed during the postpartum period. Ninety-one percent of thrombosed external hemorrhoids were observed during the first day after delivery, whereas anal fissures were distributed, with no peak, over the two months after delivery. The 2 independent risk factors for anal lesions (among obstetric, baby's, and mother's information) were dyschezia, with a 5.7 odds ratio (95 percent confidence interval, 2.7-12), and late delivery, with a 1.4 odds ratio (95 percent confidence interval, 1.05-1.9). Furthermore, many thrombosed external hemorrhoids were observed after superficial perineal tears and heavier babies (P < 0.05). Only 1 of the 33 patients with thrombosed external hemorrhoids who were observed underwent a cesarean section. CONCLUSION: One third of females have thrombosed external hemorrhoids or anal fissures in the postpartum period. The most important risk factor is dyschezia. Traumatic delivery appears to be associated with thrombosed external hemorrhoids.

Adult↗

Dienogest is as effective as triptorelin in the treatment of endometriosis after laparoscopic surgery: results of a prospective, multicenter, randomized study.

OBJECTIVE: To compare the efficacy of Dienogest versus Decapeptyl at 3.75 mg as consolidation therapy for surgery in the treatment of endometriosis. DESIGN: Multicenter, open, randomized, parallel-group clinical trial. SETTING: Volunteer patients in an academic research environment. PATIENT(S): Women with grade 2, 3, and 4 (</=70) endometriosis at initial laparoscopy. INTERVENTION(S): We provided 16 weeks of treatment with Dienogest, 1 mg tablet daily; or with Decapeptyl, 3.75 mg IM injection every 4 weeks. MAIN OUTCOME MEASURE(S): A change in the patient's Revised American Fertility Society score at the post-treatment laparoscopy. RESULT(S): From June 1994 to July 1998, 142 patients were enrolled in the trial. After exclusion for major protocol deviations, 59 patients were included in the Dienogest group and 61 in the Decapeptyl group. This study group was comparable to the first inclusion group. The patient demographic and clinical characteristics, median duration of endometriosis, Revised American Fertility Society scores, and Visual Analogic Squale (VAS) scores were comparable in both groups. Statistical analysis of efficacy was not significantly different between the two groups. Adverse events were reported by 87.7% of patients in the Dienogest group and 85.1% in the Decapeptyl group. Neither treatment affected patient body weight or vital signs. CONCLUSION(S): Dienogest is as effective as Decapeptyl for consolidation therapy after surgery for the treatment of endometriosis. The safety profile of dienogest differed from Decapeptyl (3.75 mg). Dienogest constitutes a new therapeutic alternative to the GnRH analogues.

Adolescent↗

Expression of von Willebrand's factor, CD34, CD31, and vascular endothelial growth factor in uterine leiomyomas.

OBJECTIVE: To compare the vascular parameters of uterine leiomyomas and normal myometrium, to correlate these parameters with vascular endothelial growth factor (VEGF) expression and clinical/pathological parameters, and to compare vascular parameters according to the endothelial markers used. DESIGN: An immunohistochemical technique was applied to formalin-fixed paraffin-embedded tissue samples, using antibodies against von Willebrand's factor (FvW), CD34, CD31, and VEGF. The intratumoral vascular area (VA), microvessel density (MVD), and vascular luminal area (VLA) were determined with an image analyser. SETTING: University teaching hospital. PATIENT(S): Thirty-two patients with uterine leiomyomas underwent conservative surgery. Twenty leiomyoma-free patients undergoing hysterectomy were the controls. INTERVENTION(S): Immunohistochemical and morphometrical analysis. MAIN OUTCOME MEASURE(S): Measurements of VA, MVD, and VLA. RESULT(S): The CD34 labeling showed decreased VA in myomas compared with myometrium. Decreased MVD and an increased VLA in myomas were found with FvW and CD34 labeling. The VA, MVD, and VLA were not related to VEGF expression or to clinical/pathological parameters. Similar results for VA and MVD were obtained with FvW and CD34 labeling. CONCLUSION(S): Leiomyomas have a smaller vascular area, a lower microvessel density, and a higher vascular luminal area than normal myometrium.

Antigens, CD↗

Expression of cadherins and CD44 isoforms in human endometrium and peritoneal endometriosis.

BACKGROUND: To evaluate (a) cadherins and CD44 expression in normal endometrium and in peritoneal endometriosis, and (b) to correlate, their expressions with clinicopathological parameters. METHODS: E- and N-cadherin, CD44 isoforms, CD44v3 and CD44v6 expressions were evaluated: (a) by immunoblotting in endometrium (n = 6) and in peritoneal endometriotic samples (n = 7) and, (b) by immunohistochemistry in endometrium (n = 15) and in peritoneal endometriotic samples (n = 23). RESULTS: By immunoblotting, endometrium expressed E- and N-cadherin, CD44 isoforms, CD44v3 and CD44v6. Similar results were observed in peritoneal endometriosis. By immunohistochemistry, in endometrium, E-cadherin was restricted to epithelial cells. Its expression remained constant throughout the menstrual cycle. N-cadherin was detected in both epithelial and stromal cells in the proliferative phase but was restricted to epithelial cells in the secretory phase. CD44 immunostaining was detected in the secretory but not in the proliferative phase. Decreased expression of E-cadherin (p < 0.01) and CD44 (p < 0.01) in epithelial cells was found in peritoneal endometriosis as compared with normal endometrium. In endometriotic stromal cells, decreased CD44 expression was found. In peritoneal endometriosis, we observed a decreased expression of E-cadherin in advanced stages of the disease (p < 0.01). CONCLUSION: Our results suggest that E-cadherin and CD44 proteins could be involved in the development of endometriotic lesions. Investigation of the mechanisms of altered adhesion molecule expression may contribute to the understanding of the behavior of endometriotic cells.

Adult↗

Soluble intercellular adhesion molecule 1 in umbilical cord serum: potential for the diagnosis of neonatal infections.

OBJECTIVE: To evaluate the diagnostic relevance to neonatal infections of the soluble intercellular adhesion molecule 1 (sICAM-1) cord serum level. METHODS: The case-control study included 66 term newborn infants with and without risk factors for neonatal infections. Cord blood serum determinations of white blood cell count, C-reactive protein, fibrinogen, and sICAM-1 were systematically performed associated with bacterial cultures from placenta, ears, and gastric fluids. RESULTS: 6 of 33 infants (18.2%) with risk factors were infected, and 13 (39.4%) were colonized. Two infants included in the group without infection risk factors (n = 33) were colonized. No difference in sICAM-1 cord serum levels was found according to the presence of premature rupture of membrane, fetal tachycardia >160 bpm, meconial amniotic fluid, and duration of labour >10 h. No difference in sICAM-1 was noted between infected and non-infected infants. The cord serum levels of sICAM-1 were significantly higher in infants after forceps extraction (p = 0.01). A correlation was observed between sICAM-1 and C-reactive protein cord serum levels (p = 0.004, r = 0.371) and between sICAM-1 level and neutrophil count (p = 0.01, r = 0.489). CONCLUSIONS: Our results suggest that cord serum sICAM-1 determinations have no diagnostic relevance to neonatal infection. The increase of sICAM-1 cord serum levels in infants after forceps extraction suggests its potential to evaluate cerebral trauma or hypoxia.

Bacteria↗