Decreased placental folate transporter expression and activity in first and second trimester in obese mothers.

Obese women have an approximately twofold higher risk to deliver an infant with neural tube defects (NTDs) despite folate supplementation. Placental transfer of folate is mediated by folate receptor alpha (FR-α), proton coupled folate transporter (PCFT), and reduced folate carrier (RFC). Decreased placental transport may contribute to NTDs in obese women. Serum folate levels were measured and placental tissue was collected from 13 women with normal BMI (21.9±1.9) and 11 obese women (BMI 33.1±2.8) undergoing elective termination at 8-22 weeks of gestation. The syncytiotrophoblast microvillous plasma membranes (MVM) were isolated using homogenization, magnesium precipitation, and differential centrifugation. MVM expression of FR-α, PCFT and RFC was determined by western blot. Folate transport capacity was assessed using radiolabeled methyl-tetrahydrofolate and rapid filtration techniques. Differences in expression and transport capacity were adjusted for gestational age and maternal age in multivariable regression models. P<.05 was considered statistically significant. Serum folate levels were not significantly different between groups. Placental MVM folate transporter expression did not change with gestational age. MVM RFC (-19%) and FR-α (-17%) expression was significantly reduced in placentas from obese women (P<.05). MVM folate transporter activity was reduced by-52% (P<.05) in obese women. These differences remained after adjustment for gestational age. There was no difference in mTOR signaling between groups. In conclusion, RFC and FR alpha expression and transporter activity in the placental MVM are significantly reduced in obese women in early pregnancy. These results may explain the higher incidence of NTDs in infants of obese women with adequate serum folate.

Management of lower vaginal agenesis in a patient with unicornuate uterus.

BACKGROUND: Absence of the lower vagina occurs from abnormal development of the sinovaginal bulbs and vaginal plate. CASE: We present a case of an adolescent girl, with a history of VACTERL and VATER status post flap vaginoplasty at 8 m of age and correction of vaginal-urethral fistula, with primary amenorrhea and cyclic pelvic pain. MRI showed a right hematocolpos. On exam the obstructed vagina was deviated to the right. Given prior urologic and rectal surgery, and laterality of unicornuate system, intra-operative ultrasonography (US) was performed. A needle was used to enter the inferior aspect of the obstructed vagina. A pull-through vaginoplasty was performed. SUMMARY AND CONCLUSION: Vaginal pull-through is the standard treatment for lower vaginal agenesis. In a unicornuate system, the use of intra-operative US is helpful to determine the appropriate angle of dissection.

The selective estrogen receptor modulator DT56a (Femarelle) does not affect platelet reactivity in normal or thrombophilic postmenopausal women.

OBJECTIVE: The purpose of this study was to assess the effect of DT56a (Femarelle), a selective estrogen receptor modulator, on platelet function in normal and thrombophilic women being treated for severe menopausal symptoms. METHODS: The Platelet Function Analyzer-100 (PFA-100) was used to asses platelet reactivity at baseline and after 8 weeks of treatment with Femarelle (644 mg/d in divided doses) in 25 symptomatic postmenopausal women with normal clotting times and seven symptomatic women with shortened clotting times (<61 s). The PFA-100 measure of closure time is considered equal to clotting time in assessing clotting function and platelet adhesion, aggregation, and blood coagulation factors. Closure times were measured after 3 and 8 weeks in all participants and at 1 year in the women with shortened clotting times. The nonparametric Wilcoxon signed rank test was used to assess the changes between baseline and each of the three subsequent measurements. RESULTS: Pretreatment study of all seven women with shortened closure times confirmed abnormalities associated with thrombophilia: four women were heterozygous for the factor V Leiden gene mutation, one was heterozygous for the prothrombin gene mutation, one was found to have protein S deficiency, and one had increased anticardiolipin antibodies. All participants reported improved symptoms during the treatment period. No significant change in closure times was found in the normally clotting participants after 3 or 8 weeks of Femarelle therapy (P > 0.26). No significant change in closure time was seen in the seven thrombophilic women after 3 or 8 weeks or 1 year of Femarelle treatment (P > 0.26). The regression curve for measures over time was not significant (P = 0.26). CONCLUSIONS: Femarelle, whose active ingredient is DT56a, did not adversely affect platelet reactivity as measured by PFA closure times in symptomatic thrombophilic postmenopausal women or normal controls. Femarelle, a novel selective estrogen receptor modulator that inhibits menopausal symptoms without thrombogenicity, may offer a new clinical choice for therapy of symptomatic postmenopausal women.

Radiographic and patient factors associated with pre-radiographic osteoarthritis in hip dysplasia.

BACKGROUND: Hip dysplasia leads to abnormal loading of articular cartilage, which results in osteoarthritis. The purpose of this study was to investigate the anatomic and demographic factors associated with the early onset of osteoarthritis in dysplastic hips by utilizing the delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) index as a marker of the disease. METHODS: Ninety-six symptomatic dysplastic hips in seventy-four patients were assessed with standard radiographs and a dGEMRIC scan. The lateral center-edge angle of Wiberg, the acetabular index of Tönnis, and the break in the Shenton line were measured on a standing anteroposterior radiograph. Anterior undercoverage was assessed by measuring the anterior center-edge angle on a Lequesne false-profile view. A labral tear was considered to be present when contrast agent was seen through the entire thickness of the labrum on magnetic resonance arthrography. Osteoarthritis was defined as a dGEMRIC value of <390 msec (two standard deviations below the dGEMRIC index in normal hips). RESULTS: The mean dGEMRIC index (and standard deviation) for this cohort (473 +/- 104 msec) was significantly lower than that of a morphologically normal hip (570 +/- 90 msec). The anterior center-edge angle, the joint space width, and the presence of a labral tear were all found to be associated with osteoarthritis in the univariate analysis. Multivariate analysis identified age, the anterior center-edge angle, and the presence of a labral tear as independent factors associated with osteoarthritis. A second model was fitted with omission of the anterior center-edge angle because the lateral and anterior center-edge angles were highly correlated and the lateral center-edge angle is a more common clinical measure. This model identified age, the lateral center-edge angle, and the presence of a labral tear as significant independent factors associated with osteoarthritis. CONCLUSIONS: As has been demonstrated in previous studies of the hip, this investigation showed osteoarthritis to be associated with increasing age and the severity of dysplasia, as demonstrated both by the Wiberg lateral center-edge angle and the Lequesne anterior center-edge angle. Additionally, we identified a labral tear as being a risk factor for osteoarthritis.

Measuring surgeons' treatment preferences and satisfaction with nerve reconstruction techniques for children with unique brachial plexus birth palsies.

BACKGROUND: This study surveyed microsurgeons on treatments chosen for infants with brachial plexus birth palsies who have had failure of antigravity biceps and/or triceps function due to nerve surgery or natural history. METHODS: Questionnaires were sent to surgeons participating in a prospective multicenter brachial plexus birth palsy study. With a response rate of 82 percent, the sample comprised 22 surgeons with extensive experience in treating brachial plexus birth palsy. The survey gathered collective information on two unique clinical groups: (1) infants with no antigravity biceps function but intact antigravity deltoid and radial nerve function and (2) infants with no antigravity radial nerve function (wrist and digital extension, triceps) but intact antigravity biceps and deltoid function. Analysis of data and age-based trends was performed using the Fisher's exact test. RESULTS: With failure of biceps recovery, surgeons preferred microsurgery for children 6 to 18 months old and tendon transfers for children older than 18 months. Both procedures were preferred over observation alone (p < 0.001). With regard to microsurgery techniques, with increasing age, surgeons used nerve transfers more than resected neuroma and grafting. With tendon transfers, regional transfers were performed more than 90 percent of the time at all ages. For patients with no antigravity radial nerve function, most cases at all ages were managed by observation rather than microsurgery or tendon transfers (p < 0.001). CONCLUSIONS: The authors' data indicate a general consensus in treatment choices for the two cases of microsurgical failure in infants with brachial plexus birth palsies as well as in satisfaction among experienced surgeons in using these treatments.