Novel mutation in COL1A1 associated with Osteogenesis imperfecta not compatible with life

Osteogenesis imperfecta (OI) is a skeletal dyscrasia characterized by decreased bone strength and associated fractures. Over 95% of autosomal dominant forms of this disease are associated with defects in the genes for collagen COL1A1 and COL1A2.1 The lethal type II disease has been identified antenatally by symmetrically shortened long bones and micromelia. Many reports have indicated that a femur length to abdominal circumference ratio (FL:AC) of less than 0.16 is predictive of lethality associated with OI.2,3 We report a case that presented at 20 weeks’ gestation with shortening of the lower limbs, specifically a lagging femur length and FL:AC of < 0.16. On subsequent ultrasound examinations, progressive shortening of the femur as well as shortening of the long bones of the upper extremities was documented. The thorax appeared normal until 31 weeks. The FL:AC remained below 0.16 throughout pregnancy. Workup in the neonatal period identified a novel mutation in COL1A1. The neonate was able to breathe spontaneously at birth requiring minimal respiratory support for the initial 2 weeks and lived for 26 days

Transient early preeclampsia in twin pregnancy with a triploid fetus: a case report

INTRODUCTION: Triploid pregnancies have an increased risk of early preeclampsia. Twin pregnancies consisting of one healthy fetus and one complete or partial molar, with or without a triploid fetus, are rare and management is complex. CASE PRESENTATION: A 33-year-old Caucasian woman presented with a dichorionic diamniotic twin pregnancy. One fetus showed early growth restriction resulting in fetal death at 20 weeks. The placenta was enlarged with some cysts. Chorionic villus biopsy confirmed triploidy. At 21 weeks, the patient developed preeclampsia with a blood pressure of 154/98 mmHg and proteinuria (24 hour protein excretion of 2.5 g/L), for which she was hospitalized. Without pharmacological interventions, the blood pressure normalized and proteinuria disappeared. At 35 weeks, she again developed preeclampsia. A cesarean section was performed at 38 weeks and a healthy child was born. CONCLUSIONS: Survival of the healthy fetus is possible in a twin pregnancy with a triploid fetus complicated by early preeclampsia. The pregnancy should not be terminated if the triploid twin has died and as long as conservative management is safe

Ampicillin/Sulbactam versus Cefuroxime as antimicrobial prophylaxis for cesarean delivery: a randomized study

<p>Abstract</p> <p>Background</p> <p>The efficacy and safety of a single dose of ampicillin/sulbactam compared to a single dose of cefuroxime at cord clamp for prevention of post-cesarean infectious morbidity has not been assessed.</p> <p>Methods</p> <p>Women scheduled for cesarean delivery were randomized to receive a single dose of either 3 g of ampicillin-sulbactam or 1.5 g of cefuroxime intravenously, after umbilical cord clamping. An evaluation for development of postoperative infections and risk factor analysis was performed.</p> <p>Results</p> <p>One hundred and seventy-six patients (median age 28 yrs, IQR: 24-32) were enrolled in the study during the period July 2004 - July 2005. Eighty-five (48.3%) received cefuroxime prophylaxis and 91 (51.7%) ampicillin/sulbactam. Postoperative infection developed in 5 of 86 (5.9%) patients that received cefuroxime compared to 8 of 91 (8.8%) patients that received ampicillin/sulbactam (p = 0.6). In univariate analyses 6 or more vaginal examinations prior to the operation (p = 0.004), membrane rupture for more than 6 hours (p = 0.08) and blood loss greater than 500 ml (p = 0.018) were associated with developing a postoperative surgical site infection (SSI). In logistic regression having 6 or more vaginal examinations was the most significant risk factor for a postoperative SSI (OR 6.8, 95% CI: 1.4-33.4, p = 0.019). Regular prenatal follow-up was associated with a protective effect (OR 0.04, 95% CI: 0.005-0.36, p = 0.004).</p> <p>Conclusions</p> <p>Ampicillin/sulbactam was as safe and effective as cefuroxime when administered for the prevention of infections following cesarean delivery.</p> <p>Trial registration</p> <p>Clinicaltrials.gov identifier: NCT01138852</p

The estrogen-injected female mouse: new insight into the etiology of PCOS

<p>Abstract</p> <p>Background</p> <p>Female mice and rats injected with estrogen perinatally become anovulatory and develop follicular cysts. The current consensus is that this adverse response to estrogen involves the hypothalamus and occurs because of an estrogen-induced alteration in the GnRH delivery system. Whether or not this is true has yet to be firmly established. The present study examined an alternate possibility in which anovulation and cyst development occurs through an estrogen-induced disruption in the immune system, achieved through the intermediation of the thymus gland.</p> <p>Methods, Results and Conclusion</p> <p>A putative role for the thymus in estrogen-induced anovulation and follicular cyst formation (a model of PCOS) was examined in female mice by removing the gland prior to estrogen injection. Whereas all intact, female mice injected with 20 ug estrogen at 5–7 days of age had ovaries with follicular cysts, no cysts were observed in animals in which thymectomy at 3 days of age preceded estrogen injection. In fact, after restoring immune function by thymocyte replacement, the majority of thymectomized, estrogen-injected mice had ovaries with corpora lutea. Thus, when estrogen is unable to act on the thymus, ovulation occurs and follicular cysts do not develop. This implicates the thymus in the cysts' genesis and discounts the role of the hypothalamus. Subsequent research established that the disease is transferable by lymphocyte infusion. Transfer took place between 100-day-old estrogen-injected and 15-day-old naïve mice only when recipients were thymectomized at 3 days of age. Thus, a prerequisite for cyst formation is the absence of regulatory T cells. Their absence in donor mice was judged to be the result of an estrogen-induced increase in the thymus' vascular permeability, causing de facto circumvention of the final stages of regulatory T cell development. The human thymus has a similar vulnerability to steroid action during the fetal stage. We propose that in utero exposure to excessive levels of steroids such as estrogen has a long-term effect on the ability of the thymus to produce regulatory T cells. In female offspring this can lead to PCOS.</p

Novel mutation in COL1A1 associated with Osteogenesis imperfecta not compatible with life

Osteogenesis imperfecta (OI) is a skeletal dyscrasia characterized by decreased bone strength and associated fractures. Over 95% of autosomal dominant forms of this disease are associated with defects in the genes for collagen COL1A1 and COL1A2.1 The lethal type II disease has been identified antenatally by symmetrically shortened long bones and micromelia. Many reports have indicated that a femur length to abdominal circumference ratio (FL:AC) of less than 0.16 is predictive of lethality associated with OI.2,3 We report a case that presented at 20 weeks’ gestation with shortening of the lower limbs, specifically a lagging femur length and FL:AC of < 0.16. On subsequent ultrasound examinations, progressive shortening of the femur as well as shortening of the long bones of the upper extremities was documented. The thorax appeared normal until 31 weeks. The FL:AC remained below 0.16 throughout pregnancy. Workup in the neonatal period identified a novel mutation in COL1A1. The neonate was able to breathe spontaneously at birth requiring minimal respiratory support for the initial 2 weeks and lived for 26 days

Temporal expression of inducible nitric oxide synthase in mouse and human placenta.

The aim of this study is to investigate the changes in expression and activity of inducible nitric oxide synthase (iNOS) in the developing murine embryo and mouse and human placenta. Using reverse transcription-polymerase chain reaction (RT-PCR), Northern blotting, and in-situ hybridization (ISH) we identified iNOS mRNA in mouse placenta at 9.5, 12, 14, 16, 18 and 20 days post coitum. Northern blot analysis demonstrated that the quantity of murine iNOS transcript was expressed at a stable level between days 12-20 although the level of calcium-independent NOS activity declined with advancing gestation. RT-PCR detected iNOS-specific mRNA in murine embryonic stem cells, but not in embryos at later stages (4-cell or blastocyst). ISH failed to show iNOS-specific mRNA in either murine placenta or the underlying myometrium on day 7, but did so in the trophoblast by day 9.5. Later in gestation, extensive labelling was observed in both spongiotrophoblast and trophoblast giant cells. iNOS mRNA was also detected both in immature human placentae (16-18 weeks) and at term, predominantly in syncytiotrophoblasts and placental artery smooth muscle. In conclusion, iNOS is constitutively expressed in mouse and human placenta at a time and in a location that suggests a role in placentation