Unexplained pregnancy loss: a marker of basal endothelial dysfunction?

OBJECTIVE: To compare the microparticle levels of women referred for unexplained pregnancy loss with those of parous controls. DESIGN: Incident case-control study. SETTING: University medical center. PATIENT(S): 124 women consecutively referred for unexplained pregnancy losses (two or more losses at or before 21 weeks of gestational age, or at least one later loss), and 273 parous women without pregnancy loss. INTERVENTION(S): Numeration of circulating microparticles by flow cytometry after differentiation of subpopulations according to the expression of membrane-specific antigens (CD51, CD144, or CD146 for endothelial, CD41 for platelet, CD45 and CD66b for leukocyte and neutrophil microparticles). MAIN OUTCOME MEASURE(S): Plasma levels of microparticles. RESULTS: A relative hypercoagulable state assessed by thrombin generation test had been previously reported in such cases, so we hypothesized that this could be explained by an excess of procoagulant microparticles. The study women displayed statistically significantly lower platelet and higher endothelial microparticle levels than the controls. The parameters of the thrombin generation test were only correlated with the level of endothelial microparticles, with a low coefficient of Speerman's correlation (r=0.15). CONCLUSION(S): The difference in microparticle levels between the patients and controls does not clearly explain the hypercoagulable state reported in the patients but could reflect chronic endothelium damage.

Nonvisualization of fetal gallbladder increases the risk of cystic fibrosis.

OBJECTIVE: The aim of our study is to evaluate the prevalence of cystic fibrosis (CF) in fetuses referred for genetic testing because of ultrasonographic sign (nonvisualized fetal gallbladder--NVFGB). METHOD: We reviewed the results of CFTR gene analysis over the period 2002 to 2009 in all consecutive cases referred because of NVFGB in Western France. We correlated these data with the presence of a more classical ultrasonographic finding (fetal echogenic bowel - FEB). RESULTS: Cystic fibrosis was diagnosed in 5 of the 37 fetuses with NVFGB (13.5%, 95% confidence interval (CI): [2.5%; 24.5%]) and in only 9 of the 229 other cases referred because of FEB (3.9%, 95% CI: [3.2%; 14.7%]). In our series, all CF-affected fetuses with NVFGB also had FEB. The risk of CF was 11.6-fold higher in fetuses with both indications (NVFGB + FEB) than in fetuses with isolated FEB (45.5% vs 3.9%, RR = 11.6, 95% CI: [4.7%; 28.8%], p = 0.0001). We also estimated that the residual risk of CF was less than 1 in 68 (1.5%) when a single mutation was identified in the fetus by our molecular protocol. CONCLUSION: Ultrasonographic evidence of NVFGB is an additional risk factor for CF in cases with FEB.

Cytotoxic effect of hyperthermia and chemotherapy with platinum salt on ovarian cancer cells: results of an in vitro study.

PURPOSE: Hyperthermic intraperitoneal chemotherapy is continuously under evaluation in ovarian cancer. The purpose of the present study was to evaluate the effect of chemotherapy, drug concentration and temperature. MATERIALS AND METHODS: A human ovarian carcinoma cell line was used. The effect of hyperthermia combined with chemotherapy was analyzed. RESULTS: When hyperthermia was combined with chemotherapy, the 50% lethal dose (LD(50)) decreased with the duration of exposure. The effect of temperature was similar between 39 and 43 °C for a 30-min exposure. For a 60- to 90-min exposure, the LD(50) was equivalent between 38 and 43 °C. Beyond 40 °C, an increase in platinum salt concentration was necessary to obtain similar results according to the duration of exposure. CONCLUSIONS: The cytotoxic effect of the combination seemed to be potentiated and limited at 40 °C.

[Desmoid tumor of the breast in a 9 years old little girl]. / Fibromatose mammaire chez une fillette de neuf ans.

Aggressive fibromatosis (desmoid tumour) of the breast is a rare tumour that accounts only for 0.2% of primary breast tumours. This is a benign mesenchymal tumour that develops from muscular fasciae and aponeuroses. It is characterized by its local evolution and its tendency to relapse without metastasizing. Wide radical resection should be attempted whenever possible. Positive margins at resection and reoperation are associated with a high risk of local recurrence. The role of radiotherapy and of medical treatments- especially anti-estrogens - remains unclear. We report here the case of desmoid tumour of the breast arising in a 9-year-old little girl.

Increased thrombin generation measured in the presence of thrombomodulin in women with early pregnancy loss.

Compared with 537 parous controls with no history of pregnancy loss, a lower thrombomodulin-related inhibition of the endogenous thrombin potential was measured in 264 cases with previous unexplained pregnancy loss, especially when losses occurred between 9 and 12 weeks of gestation. Adjusting age, protein S, factor VIII, factor V Leiden, and prothrombin G20210A did not change the results.

Difficult diagnosis and management of an heterokaryotypic monochorionic twin pregnancy with discordant fetal sex and 45,X/47,XYY karyotypes.

We report twins for whom ultrasound examinations revealed a Turner syndrome in the female fetus and a normal male fetus. A selective pregnancy termination was decided on the female fetus with hydrops. The death of both twins called in question the chorionic diagnosis. Amniotic fluid cytogenetic analysis revealed a 45,X karyotype in the female twin and a 47,XYY karyotype in the male twin. Molecular cytogenetic analysis on genital and renal cells showed different levels of 45,X/47,XYY mosaicism in both twins; molecular analysis on the amniocytes showed monozygosity. Monozygotic twins with discordant sex are very rare. This study showed the difficult diagnosis and management of a monochorionic twin pregnancy with discordant fetal sex.

Second-trimester prenatal screening for trisomy 21 using biochemical markers: a 7-year experience in one cytogenetic laboratory.

BACKGROUND: Screening for trisomy 21 in the second trimester of pregnancy using biochemical markers is an established part of prenatal care in many developed countries. OBJECTIVE: The present study was aimed at determining the incidence of trisomy 21 and other chromosomal abnormalities in women undergoing prenatal chromosome analysis after a second-trimester biochemical screening. RESULTS: A total of 2832 karyotypes were analyzed following a positive second-trimester maternal serum screening (risk > or = 1/250) between 1998 and 2004. Thirty-nine cases of trisomy 21 and 40 other chromosomal abnormalities were detected. The positive predictive value was 1 in 73 karyotypes for trisomy 21 and 1 in 71 for the other chromosomal abnormalities. However, a temporal decline in the detection rate of trisomy 21 was noted, from 1/63 in 1998 to 1/221 in 2004. This change was attributable to an increasing number of pregnant women having first-trimester ultrasound nuchal translucency measurement. CONCLUSION: Given the fact that nuchal translucency measurement combined with first-trimester biochemical marker screening has a positive predictive value of trisomy 21 comparable to that obtained following second-trimester biochemical screening, we should question whether to move trisomy 21 screening by maternal serum markers from the second trimester to the first trimester in conjunction with nuchal translucency measurement. Furthermore, genetic counseling prior to the amniocentesis should discuss the relatively high probability that a chromosomal abnormality other than trisomy 21 may be identified.

Diagnostic value of a negative single complete compression ultrasound of the lower limbs to exclude the diagnosis of deep venous thrombosis in pregnant or postpartum women: a retrospective hospital-based study.

OBJECTIVE: We aimed at determining whether a negative single complete compression ultrasonography (CUS) of the lower limbs veins is a safe and accurate diagnostic method to rule out the diagnosis of deep venous thrombosis in pregnant and early postpartum women. DESIGN: Hospital-based retrospective study. SETTING: The gynaecology and vascular ultrasound units of three general hospitals in western France. PATIENTS: We identified from the hospitals databases all pregnant or up to three months postpartum women who underwent CUS for a suspicion of deep venous thrombosis between January 2002 and December 2004. METHODS: Questionnaires were sent to all women with a negative CUS. Their medical records were also checked. MAIN OUTCOME MEASURES: We assessed the three-month thromboembolic risk and its 95% percent confidence interval in women left untreated on the basis of a negative single complete CUS of the lower limbs. RESULTS: During the study period, 162 pregnant or postpartum women underwent CUS for a suspicion of deep venous thrombosis. It was positive in 44 (27%). The 118 women who had a negative CUS were sent the questionnaire. Information about the three-month follow-up was found for 107 patients (91%). None of them experienced a thromboembolic event during follow-up: 0.0% (95% CI: 0.0-3.6). CONCLUSIONS: Single complete CUS of lower limbs veins appears to be a safe method to rule out the diagnosis of deep venous thrombosis in pregnant or early postpartum women. This has to be confirmed by a prospective management study with a formal follow-up.

Diagnosis and outcome of complete hydatidiform mole coexisting with a live twin fetus.

OBJECTIVE: The aim of this study was to highlight the outcome of complete hydatidiform mole (CHM) coexisting with a live co-twin. METHODS: We investigated four cases of such pregnancy by ultrasound, pathological, cytogenetic, and molecular techniques. Information on clinical follow-up and outcome was also available. RESULTS: All four pregnancies were spontaneous: two ended with the delivery of a live-born baby, while the other two were terminated because of signs of serious maternal pathology or intrauterine fetal death. The criteria for carrying on with the pregnancy are reviewed. The immediate outcome depends on the maternal criteria of serious pathology and on the likelihood of intrauterine fetal death. The risk of persistent trophoblastic disease (PTD) is the same as in the case of a singleton complete mole and also seems to be correlated with the zygosity mechanism identified by molecular analysis. CONCLUSION: Hydatiform mole with a live co-twin fetus is a rare obstetric occurrence. In the case of a normal fetal karyotype, it is justifiable to await developments in the absence of maternal complications. However, treatment criteria still need improvement and diligent maternal follow-up is always warranted in the postpartum period.

Prenatal sonographic patterns in six cases of Wolf-Hirschhorn (4p-) syndrome.

This multicentric study presents 6 cases of Wolf-Hirschhorn syndrome (deletion of 4p) detected after a sonographic prenatal diagnosis of early intrauterine growth retardation with fetal abnormalities. Standard karyotyping on regular G-banding during pregnancy was normal in half of the cases. Fortunately, the associated sonographic signs of a typical face, cystic cerebral lesions, midline fusion defects and bilateral renal hypoplasia may help to refine specific indications for high-resolution banding and molecular analysis by in situ hybridization.

Long-term tolerability of benazepril in dogs with congestive heart failure.

OBJECTIVES: To test the tolerability of long-term administration of benazepril in dogs with congestive heart failure (CHF). METHODS: The study was a prospective, randomized, double-blinded, placebo-controlled clinical trial. A total of 162 dogs with New York Heart Association (NYHA) class II-IV heart failure caused by chronic valvular disease (CVD) or dilated cardiomyopathy (DCM) were enrolled. Benazepril (minimum dosage, 0.25 mg/kg) or placebo were administered orally once daily for up to 34 months. In this paper, we report results of plasma alanine aminotransferase (ALT), creatinine, potassium and urea. RESULTS: The two groups were matched at baseline (p>/=0.18). Plasma creatinine concentrations were lower during treatment with benazepril versus placebo for all dogs (p=0.14) and every sub-group tested (NYHA II, III or IV; CVD; DCM; initial creatinine >124 mumol/L), although statistical significance was not reached (p=0.14-0.6). However, significantly (p=0.035) more cases of creatinine >124 mumol/L during treatment occurred with placebo (47%) as compared to benazepril (30%). Plasma ALT and urea values did not differ between groups for all dogs (p>0.5) or any sub-group (p=0.23-1.0). Plasma potassium values did not differ between groups for all dogs (p>0.5). Although differences approached statistical significance for potassium in some sub-groups (p=0.07-0.1), there were no consistent differences between groups. CONCLUSIONS: Benazepril was well tolerated during long-term therapy in dogs with CHF and no specific precautions appear to be necessary regarding plasma ALT, creatinine, potassium or urea. The possible action of benazepril in improving renal function (evidenced via lower plasma creatinine) merits further investigation.

Differential effects of oral and transdermal estrogen/progesterone regimens on sensitivity to activated protein C among postmenopausal women: a randomized trial.

OBJECTIVE: Activated protein C (APC) resistance not related to the factor V Leiden mutation is a risk factor for venous thrombosis. Oral estrogen replacement therapy (ERT) has been reported to induce APC resistance. Little is known about the effect of transdermal estrogen. METHODS AND RESULTS: We enrolled 196 postmenopausal women who were randomly allocated to receive either 1 mg 17beta-estradiol orally (n=63) or 50 microg 17beta-estradiol transdermally per day (n=68), both associated with 100 mg progesterone daily or placebo (n=65) for 6 months. An activated partial thromboplastin time (APTT)-based test and the effect of APC on thrombin potential (ETP) were used. Oral ERT induced an ETP-based APC resistance compared with both placebo (P=0.006) and transdermal ERT (P<0.001), but there was no significant effect of transdermal ERT compared with placebo (P=0.191). There was no significant effect of ERT on the APTT-based APC sensitivity ratio. Prothrombin fragment 1+2 plasma levels were significantly higher after 6 months of treatment in women allocated to oral ERT compared with those on placebo and transdermal ERT and were positively and significantly correlated with changes in ETP-based APC sensitivity ratio. CONCLUSIONS: Our data show that oral, unlike transdermal, estrogen induces APC resistance and activates blood coagulation. These results emphasize the importance of the route of estrogen administration.

Prenatal diagnosis of mosaic tetrasomy 8p.

Tetrasomy 8p is a rare chromosomal disorder that has only been detected in a mosaic form. At the present time, 11 cases have been reported; their phenotype included agenesis of the corpus callosum, enlarged ventricles, minor facial dysmorphism, rib and vertebral anomalies, and mild to moderate developmental delay. To the best of our knowledge, tetrasomy 8p has never been prenatally diagnosed. This 43-year-old woman was referred for amniocentesis at 20 weeks' gestation because of advanced maternal age. Amniotic fluid cells were cultured according to standard techniques by the in situ method. A supernumerary chromosomal marker was detected in a single clone of cultured amniotic cells and interpreted by RHG banding as an isochromosome of the short arm of chromosome 8 (i(8p)). The ultrasound investigation at 27 weeks gestation revealed enlarged ventricles and agenesis of the corpus callosum, which were confirmed at fetal autopsy after medical termination of the pregnancy. Chromosomal analyses, including RHG banding and FISH, of several tissues showed different levels of i(8p) mosaicism. Whereas no i(8p) was detected on cytotrophoblast nor additional amniotic fluid cells, 97% and 30% of cells from long-term cultures of placenta and lymphocytes, respectively, had the i(8p). Using DNA markers, the isochromosome 8p was interpreted as the result of a prezygotic event during maternal meiosis. Our findings suggest that the i(8p) is the subject of tissue selection. Tetrasomy 8p might be underdiagnosed during pregnancy; therefore, karyotyping on a fetal blood sample following detection of agenesis of the corpus callosum when no chromosomal abnormality has been found on the amniotic fluid cell cultures should be discussed with the parents.