Stephan Krotz

Hypertensive disease in twin pregnancies: A review

Reports over the past seventy years show that twin gestations lead to an increased risk of hypertensive disorders. Numerous studies discuss the incidence of hypertensive disease in twin versus singleton gestations, as well as effects of parity, race, age, income level, smoking, zygosity and heritability on this condition. The range of relative risk of gestational hypertension, preeclampsia and eclampsia for twin compared to singleton gestations is 1.2 to 2.7, 2.8 to 4.4 and 3.4 to 5.1 respectively. Parity, African-American ethnicity, and young maternal age are all factors that increase the relative risk of acquiring hypertensive disease to 4.0, 1.8 and 1.5 in mothers of twin gestations. Factors such as maternal smoking, income level and zygosity have a negligible effect on the relative risk of acquiring hypertensive disease in twin gestations. In addition to twin mothers exhibiting a higher incidence of hypertensive disease compared to their singleton counterparts, they also exhibit an earlier onset of hypertensive disease at both 35 and 37 weeks of gestation comparatively. Uric acid levels measured at 30-31 weeks of gestation in twin mothers predicted the onset of preeclampsia with a sensitivity of 73% and a specificity of 74%. The range of risks presented in the literature is wide and the therapies avocated are diverse. We therefore decided to summarize the risks in a comparative fashion and to review current therapeutic strategies for the convenience of clinicians who confront increasing numbers of multiple pregnancies. The tables bring all recent published risks together in the first comparative analysis in which the data has been converted to relative risks and confidence intervals. Because the literature is relatively silent on specific management of hypertensive disease in twin pregnancies, general management recommendations for singleton gestations should be used by practitioners caring over twin gestations.

Breast cancer-specific expression of the Candida albicans cytosine deaminase gene using a transcriptional targeting approach.

We constructed a series of adenoviral (Ad) vectors that express the Candida albicans cytosine deaminase (CD) suicide gene under the transcriptional control of either the human α-lactalbumin (ALA) or ovine β-lactoglobulin (BLG) promoter (Ad.ALA.CD and Ad.BLG.CD, respectively). The Ad.ALA.CD and the Ad.BLG.CD vectors converted the prodrug 5-fluorocytosine (5-FC) to the toxic nucleotide analog 5-fluorouracil in a breast cancer cell-specific manner, with a conversion rate of 40% and 52% in T47D cells and 50% and 41% in MCF7 cells, respectively. No significant conversion (≤3%) was observed in an immortalized nontumorigenic breast epithelial cell line (MCF10A) and a human osteosarcoma cell line (U2OS). Adenovirus vector-based prodrug conversion of the 5-FC in T47D and MCF7 in the presence of 1 mg/mL of 5-FC led to cytotoxicity that resulted in a nearly complete cell death (≥90%) after 5 days, whereas MCF10A and U2OS cells remained resistant (≤10%). Nude mice harboring T47D-derived breast tumors that were injected intratumorally (i.t.) with therapeutic adenovirus vectors at a dose of 2 × 108 plaque-forming units and treated systemically with 5-FC at a concentration of 500 mg/kg/day showed a marked reduction in tumor mass within 30 days when compared with animals that received vector alone. Animal survival was significantly prolonged after 72 days in mice treated with therapeutic vectors in conjunction with prodrug when compared with control animals. These preclinical data are sufficiently promising to warrant further studies of this transcriptional targeting approach to breast cancer treatment.

Use of in-cycle antimüllerian hormone levels to predict cycle outcome

OBJECTIVE The goal of this work is to expand the usefulness of antimüllerian hormone (AMH) in predicting in vitro fertilization cycle outcome by demonstrating that AMH concentration obtained in an ongoing treatment cycle predicts both oocyte number and pregnancy. STUDY DESIGN Serum samples were obtained from 190 in vitro fertilization patients at onset of follicle-stimulating hormone stimulation. These were analyzed retrospectively during a single cycle in which clinicians were blinded to the results. Our major outcome measures were the number of oocytes obtained and ongoing pregnancy. RESULTS Patients with an initial AMH concentration of >3 ng/mL were found to produce a mean of 19.8 oocytes and had an ongoing pregnancy rate of 60.3%. In contrast, those with AMH values of ≤1 ng/mL yielded a mean of 6.2 oocytes and had an ongoing pregnancy rate of 23.4% (P < .0001 for both). CONCLUSION Greater AMH serum concentration strongly predicts an increased number of oocytes and ongoing pregnancy (P ≤ .0001).

Isolated low second-trimester maternal serum β-human chorionic gonadotropin is not associated with adverse pregnancy outcome☆

OBJECTIVE We investigated whether low human chorionic gonadotropin from maternal serum screening is associated with adverse pregnancy outcome. STUDY DESIGN Women between 15 and 20 completed weeks of gestation who had a maternal serum screen performed from June 1999 to November 2001 were studied. Cases included women with human chorionic gonadotropin values of <or=0.5 multiples of the median, alpha-fetoprotein values of >0.5 and <2.0 multiples of the median, and estriol values of >0.6 and <2.0 multiples of the median. Control subjects were selected randomly from the population of women with normal values for all three analytes. RESULTS There were 146 case subjects and 292 control subjects. There was no increased risk in the study group compared with the control subjects for preterm delivery, intrauterine fetal death, low birth weight, abruptio placentae, preeclampsia, or preterm premature rupture of membranes. CONCLUSION An isolated low human chorionic gonadotropin level from second-trimester maternal serum screening is not associated with adverse pregnancy outcome.

Expression and localization of the novel and highly conserved gametocyte-specific factor 1 during oogenesis and spermatogenesis

OBJECTIVE To determine the onset of gametocyte-specific factor 1 (Gtsf1) expression in embryogenesis and its relation to Nobox; and to determine its localization during gonadal development and gametocyte maturation. DESIGN Developmental animal study. SETTING University reproductive biology laboratory. ANIMAL(S) Mice ranging in age from embryonic day 12.5 to 8 weeks. INTERVENTION(S) Polymerase chain reaction and quantitative polymerase chain reaction were performed to determine the onset of and relative messenger RNA expression. Western blot was performed to confirm protein expression and antibody specificity. In situ hybridization and immunohistochemistry were used determine localization of expression. MAIN OUTCOME MEASURE(S) Gtsf1 messenger RNA expression levels during embryogenesis through adulthood in wild-type mice and in newborn Nobox knockout mice; GTSF1 expression and localization in postnatal mice. RESULT(S) Gtsf1 functions downstream of Nobox and is highly expressed in embryonic male and female gonads, localizing to germ cells throughout development. GTSF1 expression is confined to the cytoplasm in all stages of postnatal oocyte maturation and to prespermatogonia during early postnatal testicular development. CONCLUSION(S) The expression pattern of Gtsf1 and its high conservation suggests that it may play an important role in germ cell development. Further characterization of Gtsf1 may elucidate mechanisms involved in premature ovarian failure.