Cerebral Palsy

BACKGROUND: This study was conducted to evaluate the occurrence and fate of fetal lumbar rib induced by Scutellariae radix (SR) in rats. METHODS: Water extracts of SR were orally administered to pregnant rats from day 7 to day 17 of gestation at a dose of 186 mg/kg/day, equivalent to 25 g/kg of starting material, representing a 100-fold increase over typical human intake level. RESULTS: The incidence of fetal lumbar rib in the SR-treated group was increased on gestational day 20 and then decreased on postnatal day 50. The weight of fetuses in the SR-treated group tended to be less than that in the control group. Alkaline phosphatase in SR-treated dams was increased on gestational day 20, but was decreased on postnatal day 50. There were no significant differences between the vehicle control and SR-treated groups in maternal body weight, embryological, histopathological, hematological, and serum biochemical changes. CONCLUSIONS: The present data suggest that the appearance of lumbar rib induced by SR is a transient fetal variation rather than teratogenicity or maternal toxicity. Birth Defects Res (Part B) 89:201-206, 2010. (c) 2010 Wiley-Liss, Inc.

BACKGROUND:: Nearly half of women treated with aromatase inhibitors (AI) develop AI-associated musculoskeletal symptoms (AIMSS) such as arthralgias, but to the authors’ knowledge the etiology is unclear. The upper extremities are frequently affected, especially the wrists, hands, and fingers. AI use may also increase the risk of developing carpal tunnel syndrome. Tendon sheath fluid and tenosynovial changes have been demonstrated by imaging symptomatic patients who were treated with AIs. The authors hypothesized that these abnormalities are correlated with AIMSS. METHODS:: Thirty consecutive patients in whom adjuvant therapy with letrozole or exemestane was initiated on a prospective clinical trial enrolled in a pilot study evaluating tendon and joint abnormalities at baseline and after 3 months of AI therapy. Patients underwent high-resolution ultrasonography of the wrists bilaterally and completed the Health Assessment Questionnaire (HAQ) and pain Visual Analog Scale (VAS). AIMSS were defined as an increase in the HAQ or VAS score during AI therapy that exceeded a predefined cutoff. RESULTS:: Twenty-five patients completed both the baseline and 3-month assessments. During the first 12 months of AI therapy, 15 patients developed AIMSS, and 13 discontinued therapy because of musculoskeletal symptoms. There was a trend toward an association between the presence of tendon sheath abnormalities on wrist ultrasound at baseline and the development of AIMSS (P = .06). CONCLUSIONS:: Clinically relevant musculoskeletal symptoms develop in women treated with AIs, leading to treatment discontinuation in a substantial percentage of these patients. However, in the current study, patient-reported symptoms were not found to be associated with changes visible on wrist ultrasonography. Cancer 2010. (c) 2010 American Cancer Society.

OBJECTIVE: To determine the need for fetal karyotyping in cases of an isolated single umbilical artery (SUA) identified during the second-trimester routine anomaly scan. METHODS: All patients booked for antenatal care and delivery in our hospital are offered two ultrasound scans in pregnancy, one at 11-13 weeks as part of screening for chromosomal defects ()and another at 20-23 weeks for detailed fetal examination. In addition we examine patients referred from other hospitals because of suspected fetal abnormalities during their routine second-trimester scan. We performed a search of the database to retrieve all cases with a SUA and reviewed the ultrasound findings, fetal karyotype and pregnancy outcome. RESULTS: There were 643 cases with SUA, including 424 (65.9%) where the condition was isolated, 133 (20.7%) with one major fetal defect and 86 (13.4%) with multiple defects. The incidence of chromosomal abnormalities was 0% in the isolated SUA group, 3.7% in those with one defect and 50.7% in those with multiple defects. The commonest chromosomal abnormalities were trisomy 18, trisomy 13 and triploidy accounting for 82.9% of cases. CONCLUSION: The finding of a SUA should prompt the sonographer to search for fetal defects and if these are found the risk for chromosomal abnormalities is increased. In cases of apparently isolated SUA there is no evidence of increased risk of chromosomal abnormalities. Copyright (c) 2010 ISUOG. Published by John Wiley & Sons, Ltd.

BACKGROUND: Nitrofen is a diphenyl ether that induces congenital diaphragmatic hernia (CDH) in rodents. Its mechanism of action has been hypothesized as inhibition of the retinaldehyde dehydrogenase (RALDH) enzymes with consequent reduced retinoic acid signaling. METHODS: To determine if nitrofen inhibits RALDH enzymes, a reporter gene construct containing a retinoic acid response-element (RARE) was transfected into HEK-293 cells and treated with varying concentrations of nitrofen in the presence of retinaldehyde (retinal). Cell death was characterized by caspace-cleavage microplate assays and terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) assays. Ex vivo analyses of cell viability were characterized in fetal rat lung explants using Live/Dead staining. Cell proliferation and apoptosis were assessed using fluorescent immunohistochemistry with phosphorylated histone and activated caspase antibodies on explant tissues. Nile red staining was used to identify intracellular lipid droplets. RESULTS: Nitrofen-induced dose-dependent declines in RARE-reporter gene expression. However, similar reductions were observed in control-reporter constructs suggesting that nitrofen compromised cell viability. These observed declines in cell viability resulted from increased cell death and were confirmed using two independent assays. Ex vivo analyses showed that mesenchymal cells were particularly susceptible to nitrofen-induced apoptosis while epithelial cell proliferation was dramatically reduced in fetal rat lung explants. Nitrofen treatment of these explants also showed profound lipid redistribution, primarily to phagocytes. CONCLUSIONS: The observed declines in nitrofen-associated retinoic acid signaling appear to be independent of RALDH inhibition and likely result from nitrofen induced cell death/apoptosis. These results support a cellular apoptotic mechanism of CDH development, independent of RALDH inhibition. Birth Defects Res (Part B) 89:223-232, 2010. (c) 2010 Wiley-Liss, Inc.

BACKGROUND: Prenatal exposure to methylnitrosourea (MNU), an alkylating agent, induces microcephaly in mice. However, its pathogenetic mechanism has not been clarified, especially that in the development of the cerebral cortex. METHODS: ICR mice were treated with MNU at 10 mg/kg intraperitoneally on day 13.5 or 15.5 of gestation, and the embryos were observed histologically 24 hr after treatment with MNU or at term. To clarify the pathogenesis of microcephaly and histological changes, especially apoptosis, neurogenesis, and neural migration/positioning, we performed histological analysis employing a cell-specific labeling experiment using thymidine-like substances (BrdU, CldU, and IdU) and markers of neurons/neural stem cells. RESULTS: Histological abnormalities of the dorsal telencephalon, and the excessive cell death of proliferative neural progenitor/stem cells were noted in the MNU-treated embryos. The highest frequencies of cell death occurred at 36 hr after MNU treatment, and little or no neurogenesis was observed in the ventricular zone of the dorsal telencephalon. Abnormality of the radial migration was caused by the reduction of radial fibers in the radial glias. Birth-date analysis revealed the abnormal positioning of neurons and aberrant lamination of the cerebral cortex. CONCLUSIONS: Our data suggest that prenatal exposure to MNU induces the excessive cell death of neural precursor/stem cells, and the defective development of the cerebral cortex, resulting in microcephalic abnormalities. Birth Defects Res (Part B) 89:213-222, 2010. (c) 2010 Wiley-Liss, Inc.

INTRODUCTION: Ayahuasca is a psychotropic plant beverage initially used by shamans throughout the Amazon region during traditional religious cult. In recent years, ayahuasca has also been used in ceremonies of a number of modern syncretic religious groups, including pregnant women. However, no documented study has been performed to evaluate the risk of developmental toxicity of ayahuasca. METHODS: In the present work, maternal and developmental toxicity was evaluated in Wistar rats. Ayahuasca was administered to pregnant rats in three different doses [the equivalent typical dose (TD) administered to humans, five-fold TD and 10-fold TD] during the gestational period (6-20 days). RESULTS: Dams treated with the highest ayahuasca dose showed maternal toxicity with decrease of weight gain and food intake. Visceral fetal findings were observed in all treatment groups. Skeletal findings were observed in the intermediate- and high-dose groups. The fetuses deriving from the highest dose group also presented a decrease in body weight. CONCLUSIONS: From these results, it is possible to conclude that there is a risk of maternal and developmental toxicity following ayahuasca exposure and that the level of toxicity appears to be dose-dependent. Birth Defects Res (Part B) 89:207-212, 2010. (c) 2010 Wiley-Liss, Inc.

Previous studies demonstrated that induced pluripotent stem (iPS) cells could produce viable mice through tetraploid complementation, which was thought to be the most stringent test for pluripotency. However, these highly pluripotent iPS cells were previously reported to be generated from fibroblasts of embryonic origin. Achieving fully pluripotent iPS cells from multiple cell types, especially easily accessible adult tissues, will lead to a much greater clinical impact. We successfully generated high-pluripotency iPS cells from adult tail tip fibroblasts (TTF) that resulted in viable, full-term, fertile TTF-iPS animals with no obvious teratoma formation or other developmental abnormalities. Comparison of iPS cells from embryonic origin (MEF), progenitor cells (neural stem cells) or differentiated somatic cells (TTF) reveals that fully pluripotent developmental potential can be reached by each cell type, although with different induction efficiencies. This work provides the means for studying the mechanisms and regulation of direct reprogramming, and has encouraging implications for future clinical applications and therapeutic interventions.

PURPOSE: Decreased ventilation is observed on chest radiographs as small changes in X-ray translucency, and ventilatory impairments can therefore be detected by analyzing the distribution of respiratory-induced changes in pixel value. This study was performed to develop a ventilatory impairment detection method based on the distribution of respiratory-induced changes in pixel values. METHODS: Sequential chest radiographs during respiration were obtained using a dynamic flat panel detector system. Respiratory-induced changes in pixel value were measured in each local area and then compared for symmetrical positions in both lungs, which were located at the same distance from the axis of the thorax at the same level. The right-left symmetry was assessed in 20 clinical cases (Abnormal, 14; Normal, 6). RESULTS: In normal controls, the distribution was symmetrical, and there were good correlations of the pixel value changes in both lungs at symmetrical positions (r = 0.66+/-0.05). In contrast, abnormal cases did not show a symmetrical distribution of pixel value changes (r = 0.40+/-0.23) due to ventilation abnormalities observed as reductions in pixel value changes. CONCLUSIONS: Ventilatory impairment could be detected as deviation from the right-left symmetry of respiratory-induced changes in pixel value. In particular, the present method could be useful for detecting unilateral abnormalities. However, to detect bilateral abnormalities, further studies are required to develop multilevel detection methods combined with several methods of pattern analysis.

PURPOSE: The goal is to automatically detect anomalous vascular cross-sections to attract the radiologist’s attention to possible lesions and thus reduce the time spent to analyze the image volume. MATERIALS AND METHODS: We assume that both lesions and calcifications can be considered as local outliers compared to a normal cross-section. Our approach uses an intensity metric within a machine learning scheme to differentiate normal and abnormal cross-sections. It is formulated as a Density Level Detection problem and solved using a Support Vector Machine (DLD-SVM). The method has been evaluated on 42 synthetic phantoms and on 9 coronary CT data sets annotated by 2 experts. RESULTS: The specificity of the method was 97.57% on synthetic data, and 86.01% on real data, while its sensitivity was 82.19 and 81.23%, respectively. The agreement with the observers, measured by the kappa coefficient, was substantial (kappa = 0.72). After the learning stage, which is performed off-line, the average processing time was within 10 s per artery. CONCLUSIONS: To our knowledge, this is the first attempt to use the DLD-SVM approach to detect vascular abnormalities. Good specificity, sensitivity and agreement with experts, as well as a short processing time, show that our method can facilitate medical diagnosis and reduce evaluation time by attracting the reader’s attention to suspect regions.