Antenatal management of recurrent fetal goitrous hyperthyroidism associated with fetal cardiac failure in a pregnant woman with persistent high levels of thyroid-stimulating hormone receptor antibody after ablative therapy.

High titer of maternal thyroid-stimulating hormone receptor antibody (TRAb) in patients with Graves' disease could cause fetal hyperthyroidism during pregnancy. Clinical features of fetal hyperthyroidism include tachycardia, goiter, growth restriction, advanced bone maturation, cardiomegaly, and fetal death. The recognition and treatment of fetal hyperthyroidism are believed to be important to optimize growth and intellectual development in affected fetuses. We herein report a case of fetal treatment in two successive siblings showing in utero hyperthyroid status in a woman with a history of ablative treatment for Graves' disease. The fetuses were considered in hyperthyroid status based on high levels of maternal TRAb, a goiter, and persistent tachycardia. In particular, cardiac failure was observed in the second fetus. With intrauterine treatment using potassium iodine and propylthiouracil, fetal cardiac function improved. A high level of TRAb was detected in the both neonates. To the best of our knowledge, this is the first report on the changes of fetal cardiac function in response to fetal treatment in two siblings showing in utero hyperthyroid status. This case report illustrates the impact of prenatal medication via the maternal circulation for fetal hyperthyroidism and cardiac failure.

Congenitally corrected transposition of the great arteries.

Congenitally corrected transposition of the great arteries (cTGA) is an uncommon cardiac malformation characterized by discordant atrioventricular and ventriculoarterial connections. Most cases of cTGA are associated with cardiac anomalies. As the ventricular outflow tract may appear to arise correctly from the right and left ventricles, cases of cTGA with a mild associated anomaly are rarely detected prenatally. Parallel vessels are evident in cTGA, but this sign is also present in complete TGA. We report a case of cTGA diagnosed in utero at 29 weeks' gestation. The fetus was diagnosed as TGA and referred to our hospital at 28 weeks' gestation. cTGA was found at 29 weeks' gestation in our hospital, and no additional cardiac anomalies were seen prenatally. After birth, patent ductus arteriosus with bidirectional flow was present. Careful examination of the four-chamber view suggested atrioventricular discordance. Identification of a parallel course of the great vessels, with the aorta anterior and to the left of the pulmonary trunk (l-transposition), may help accurate prenatal diagnosis of cTGA.

Molecular mechanisms of how mercury inhibits water permeation through aquaporin-1: understanding by molecular dynamics simulation.

Aquaporin (AQP) functions as a water-conducting pore. Mercury inhibits the water permeation through AQP. Although site-directed mutagenesis has shown that mercury binds to Cys189 during the inhibition process, it is not fully understood how this inhibits the water permeation through AQP1. We carried out 40 ns molecular dynamics simulations of bovine AQP1 tetramer with mercury (Hg-AQP1) or without mercury (Free AQP1). In Hg-AQP1, Cys191 (Cys189 in human AQP1) is converted to Cys-SHg+ in each monomer. During each last 10 ns, we observed water permeation events occurred 23 times in Free AQP1 and never in Hg-AQP1. Mercury binding did not influence the whole structure, but did induce a collapse in the orientation of several residues at the ar/R region. In Free AQP1, backbone oxygen atoms of Gly190, Cys191, and Gly192 lined, and were oriented to, the surface of the water pore channel. In Hg-AQP1, however, the SHg+ of Cys191-SHg+ was oriented toward the outside of the water pore. As a result, the backbone oxygen atoms of Gly190, Cys191, and Gly192 became disorganized and the ar/R region collapsed, thereby obstructing the permeation of water. We suggest that mercury disrupts the water pore of AQP1 through local conformational changes in the ar/R region.

Beta cell dysfunction and its clinical significance in gestational diabetes.

The aim of this study is to explore beta cell dysfunction and its clinical significance in gestational diabetes mellitus (GDM). We assessed insulin sensitivity and insulin secretion in a total of 277 Japanese women between 24 and 27 weeks of pregnancy who underwent a 2 h, 75 g oral glucose tolerance test (OGTT) because of an abnormal result on a 1 h 50 g oral glucose challenge conducted as part of a standard screening for GDM. Insulin sensitivity was evaluated by an insulin sensitivity index derived from OGTT (IS(OGTT)), whereas insulin secretion was calculated as a ratio of the total area under the insulin curve to the total area under the glucose curve (AUC(ins/glu)). Beta cell function in relation to insulin sensitivity (i.e. disposition index) was derived from the product of insulin sensitivity and insulin secretion (i.e. AUC(ins/glu) × IS(OGTT)). In women diagnosed with GDM (n=57), the disposition index was significantly lower than that in those without GDM, irrespective of obesity. The disposition index in women with GDM was significantly correlated with levels of fasting and mean preprandial capillary glucose and HbA1c before initiating insulin therapy (r = -0.45, -0.38, -0.49, respectively). Furthermore, there was a significant correlation between the disposition index and total insulin dosage to achieve glycemic goal (r = -0.41). In conclusion, we demonstrated beta cell dysfunction in Japanese women with GDM irrespective of obesity. The level of beta cell dysfunction in GDM was associated with the severity of glucose intolerance and total insulin dosage required. These findings underpin clinical significance of beta cell dysfunction in GDM.

Phosphorylation in the C-terminal domain of Aquaporin-4 is required for Golgi transition in primary cultured astrocytes.

Aquaporin-4 (AQP4) is expressed in the perivascular and subpial astrocytes end-feet in mammalian brain, and plays a critical component of an integrated water and potassium homeostasis. Here we examine whether AQP4 is phosphorylated in primary cultured mouse astrocytes. Astrocytes were metabolically labeled with [(32)P]phosphoric acid, then AQP4 was immunoprecipitated with anti-AQP4 antibody. We observed that AQP4 was constitutively phosphorylated, which is reduced by treatment with protein kinase CK2 inhibitors. To elucidate the phosphorylation of AQP4 by CK2, myc-tagged wild-type or mutant AQP4 was transiently transfected in primary cultured astrocytes. Substitution of Ala residues for four putative CK2 phosphorylation sites in the C terminus abolished the phosphorylation of AQP4. Immunofluorescent microscopy revealed that the quadruple mutant was localized in the Golgi apparatus. These observations indicate that the C-terminal domain of AQP4 is constitutively phosphorylated at least in part by protein kinase CK2 and it is required for Golgi transition.

Fetal stomach paracentesis in combined duodenal and esophageal atresia.

Fetuses with concomitant duodenal atresia (DA) and esophageal atresia (EA) might develop in utero gastric rupture as well as neonatal respiratory complication due to dilated stomach and duodenum. Our patient with the typical "double bubble" appearance was highly suspected to have DA in the second trimester. Follow-up examinations revealed a massively dilated stomach and duodenum with a dilated distal esophagus, indicating concomitant DA and EA. With advancing pregnancy, the fetal abdomen progressively increased in size by retention of fluid in the closed loop of DA and EA. To avoid gastric perforation, prenatal stomach paracentesis using an ultrasound-guided needle was performed three times until delivery. A male neonate born at 37 weeks gestation showed no respiratory complication. Perinatal clinical features and operative findings revealed combined DA and EA (gross type A). He was successfully managed with duodenoduodenostomy, followed by esophago-esophagostomy. On fetal sonography, the marked "double bubble" appearance and the cystic structure presenting peristalsis-like movement above the diaphragm were indicative of concomitant DA and EA. Fetal stomach paracentesis could contribute to the improvement of perinatal outcomes in fetuses with this pathological condition.

Ritodrine for intractable uterine pain due to extrapelvic malignant tumor metastases: a case report.

BACKGROUND: Effective pain management is an essential component of cancer treatment as approximately 75% of all cancer patients experience excruciating nociceptive pain even at maximum safe doses of nonsteroidal anti-inflammatory drugs and/or opioids. We report a case where ritodrine hydrochloride effectively controlled refractory pain due to uterine metastases from thymic carcinoma. CASE PRESENTATION: A 40-year-old woman presented at our hospital with chest discomfort, severe right femoral pain, and intermittent hypogastralgia. Computed tomography, magnetic resonance imaging, and positron emission tomography revealed a large mass in the anterior mediastinum, multiple nodules in the lungs, and multiple metastases on the uterus, lumbar vertebrae, and pelvic bones. Needle biopsies of the mediastinal and uterine cervical tumors revealed undifferentiated carcinoma of the thymus metastasizing to the uterus. Oxycodone and nonsteroidal anti-inflammatory drugs relieved the right femoral pain but not the hypogastralgia. We speculated that hypogastralgia did not result from somatalgia but from splanchnodynia. Ritodrine was administered in an effort to inhibit uterine contractions and to reduced the refractory pain and improved her quality of life. CONCLUSION: Ritodrine relieved the pain caused by uterine contraction due to metastases and enhanced the quality of life.

Comparison of the right and left ventricular performance during the fetal development using velocity vector imaging.

BACKGROUND: Studies on myocardial characteristics examined by speckle-tracking echocardiography are limited. AIMS: To compare myocardial performance between the right and left ventricles during the fetal development using velocity vector imaging (VVI). SUBJECTS AND STUDY DESIGN: Echocardiograms of 95 uncomplicated singleton fetuses (19-36 weeks pregnancy) were retrospectively analyzed by VVI to measure global longitudinal peak velocity, strain, and strain rate of both the right ventricle (RV) and left ventricle (LV). The regional values were calculated for three segments (base, mid, and apex) of the ventricular free wall and segment. OUTCOME MEASURES: The VVI-derived measurements were examined for gestational age and compared between ventricles. RESULTS: The global peak systolic and diastolic velocity values of both ventricles significantly increased over gestation examined, whereas the global systolic strain and strain rate were stable (RV: strain -22.6 ± 5.0%, strain rate -2.6 ± 0.7/s; LV: strain -21.5 ± 5.6%, strain rate -2.5 ± 0.7/s). Compared to the LV, the RV showed significantly higher global velocity in systole and diastole (P = 0.001 for systole, P < 0.001 for diastole). The global systolic velocity of the LV increased close to the RV toward term, whereas the RV was dominant in diastole throughout the examined gestation. Basal strain and strain rate in the RV were significantly greater than that of the LV, although there were no significant differences in the middle and apical values between ventricles. CONCLUSION: Our findings suggest the RV predominance of longitudinal contraction and dilatation, compared to the LV in uncomplicated fetuses.