Cerebral Palsy

BACKGROUND: Women of childbearing age are commonly prescribed medications by primary care providers (PCPs) that may cause birth defects if used during pregnancy. METHODS: To identify what PCPs perceive as barriers to and potential facilitators of providing counseling to women of childbearing age when teratogenic medications are prescribed, we conducted eight focus groups with 48 PCPs recruited from four clinical settings in Pittsburgh, Pennsylvania. We explored PCPs’ experiences counseling women about teratogenic medications. Each focus group was audio-recorded, transcribed, and coded using a grounded theory approach by three independent coders. RESULTS: PCPs feel responsible for counseling women when they prescribe medications that may cause birth defects, but note difficulties identifying clinically relevant sources of information on teratogenicity. Other barriers to providing counseling include limited visit times and lack of reimbursement for preconception or teratogenic risk counseling. PCPs find it challenging to identify patients who may become pregnant and who therefore need contraceptive and/or teratogenic risk counseling. PCPs expressed a desire for online resources that could be used when explaining medication risks to patients. PCPs feel that the development of patient information materials, electronic decision support tools, clinical care systems that routinely assess patients’ pregnancy risk, and changes in the reimbursement structure may facilitate counseling patients about teratogenic risks. CONCLUSIONS: PCPs perceive themselves as playing an important role in providing their patients information on risk of medication-induced birth defects. To ensure safe prescription of teratogenic medications, PCPs suggest interventions at both the clinic and healthcare system levels. Birth Defects Research (Part A), 2009. (c) 2009 Wiley-Liss, Inc.

The majority of ventricular septal defects (VSDs) are perimembranous, accounting for 75-80% of all VSDs. The objective of this study was to investigate occluder selection and transcatheter closure technique for multi-hole perimembranous VSD with aneurysm, and to evaluate clinical efficacy and safety. Patients with multi-hole VSDs and aneurysm (n = 64) were selected for the procedure using transthoracic echocardiography. Double-disc symmetrical, small-waist double-disc asymmetrical and zero eccentricity occluders were selected based on left ventricular angiography. The closure was successful in 63 of 64 patients (98%). The double-disc symmetrical occluder was used in 16 cases, the small-waist double-disc asymmetrical occluder in 42 cases, and the zero eccentricity occluder in 8 cases (2 occluder types were used in 2 cases). Fifteen minutes after the procedure, 52 cases had no residual shunt and 12 had a trace amount of residual shunt. The residual shunt disappeared in five cases 5-7 days post procedure, with a trace amount of shunt remaining in seven cases. Transient conduction abnormalities related to the procedure occurred in six patients; however, none required permanent pacemaker implantation. At the 1-month, 6-month, 1-year, 2-year, and 3-year follow-up visits, echocardiography indicated that the position of the occluders was fixed, and there were no complications including residual shunt, newly developed atrioventricular block, thromboembolism, or bacterial endocarditis. The study results indicate that left ventricular angiography is useful in selecting the most appropriate device for transcatheter closure of multi-hole perimembranous VSD with aneurysm. The transcatheter closure procedure is safe and effective with little residual shunt and no major complications for up to 3 years of follow-up.

Autism is a behaviorally defined disorder with deficits in social interaction, communication, atypical behaviors, and restricted areas of interest. Postmortem studies of the brain in autism have shown a broad spectrum of abnormalities in the cerebellum and neocortex, involving limbic regions such as anterior cingulate cortex (ACC, Brodmann’s area 24). Using stereological techniques, we analyzed quantitatively cytoarchitectonic subdomains of the ACC (areas 24a, b, c) with regard to cell packing density and cell size. Microscopic examination of the ACC was also done to identify any neuropathologies. Results showed a significant decrease in cell size in layers I-III and layers V-VI of area 24b and in cell packing density in layers V-VI of area 24c. Direct comparisons revealed irregular lamination in three of nine autism brains and increased density of neurons in the subcortical white matter in the remaining cases. Because previous studies have suggested that von Economo neurons (VENs) may be altered in autism, a preliminary study of their density and size was undertaken. VEN density did not differ between autism and control brains overall. However, among the nine autism cases, there were two subsets; three brains with significantly increased VEN density and the remaining six cases with reduced VEN density compared to controls. Collectively, the findings of this pilot study may reflect the known heterogeneity in individuals with autism and variations in clinical symptomotology. Further neuroanatomic analyses of the ACC, from carefully documented subjects with autism, could substantially expand our understanding of ACC functions and its role in autism.

OBJECTIVE: To examine whether the presence of high risk-human papilloma virus (HR-HPV) after conization of the cervix was a risk factor for persistence or recurrence of cervical intraepithelial neoplasia (CIN) and whether HR-HPV test could be a guideline for post-therapy surveillance. METHODS: The study retrospectively analyzed data from 243 patients who underwent LLETZ or CKC of the cervix due to CIN. RESULTS: A positive HR-HPV test result which was performed between 3 and 6 months after procedure was a risk factor for persistent or recurrent cytological (p<0.001, odds ratio [OR]=22.51, 95% confidence interval [CI]=9.74-52.02) and pathological (p<0.001, OR=18.28, 95% CI=5.55-60.20) abnormalities. CONCLUSION: HR-HPV positive patients between 3 and 6 months after procedure should undergo frequent and meticulous post-therapy surveillance, while HR-HPV negative patients do not require such high-level surveillance and could undergo routine surveillance.

The aim of this study was to determine the effects of rice bran oil (RBO) on lipid metabolism and insulin resistance in rats with streptozotocin/nicotinamide-induced type 2 diabetes mellitus (T2DM). Rats were divided into two groups: the control group (15% soybean oil, contains 0 g gamma-oryzanol and 0 g gamma-tocotrienol/150 g oil for 5 weeks) and the RBO group (15% RBO, contains 5.25 g gamma-oryzanol and 0.9 g gamma-tocotrienol/150 g oil for 5 weeks). Compared with the control group, the RBO group had a lower plasma nonesterified fatty acid concentration, ratio of total to high-density-lipoprotein cholesterol, hepatic cholesterol concentration, and area under the curve for insulin. The RBO group had a higher high-density-lipoprotein cholesterol concentration and greater excretion of fecal neutral sterols and bile acid than did the control group. RBO may improve lipid abnormalities, reduce the atherogenic index, and suppress the hyperinsulinemic response in rats with streptozotocin/nicotinamide-induced T2DM. In addition, RBO can lead to increased fecal neutral sterol and bile acid excretion.

BACKGROUND: Developmental exposure to a wide variety of developmental neurotoxicants, including organophosphate pesticides, evokes late-emerging and persistent abnormalities in acetylcholine (ACh) systems. We are seeking interventions that can ameliorate or reverse the effects later in life. OBJECTIVES: We administered parathion to neonatal rats and then evaluated whether a high-fat diet begun in adulthood could reverse the effects on ACh systems. METHODS: Neonatal rats received parathion on postnatal days 1-4 at 0.1 or 0.2 mg/kg/day, straddling the cholinesterase inhibition threshold. In adulthood, half the animals were switched to a high-fat diet for 8 weeks. We assessed three indices of ACh synaptic function: nicotinic ACh receptor binding, choline acetyltransferase activity, and hemicholinium-3 binding. Determinations were performed in brain regions comprising all the major ACh projections and cell bodies. RESULTS: Neonatal parathion exposure evoked widespread abnormalities in ACh synaptic markers, encompassing effects in brain regions possessing ACh projections and ACh cell bodies. In general, males were affected more than females. Of 17 regional ACh marker abnormalities (10 male, 7 female), 15 were reversed by the high-fat diet. CONCLUSIONS: A high-fat diet reverses neurodevelopmental effects of neonatal parathion exposure on ACh systems. This points to the potential for nonpharmacologic interventions to offset the effects of developmental neurotoxicants. Further, cryptic neurodevelopmental deficits evoked by environmental exposures may thus engender a later preference for a high-fat diet to maintain normal ACh function, ultimately contributing to obesity.

Cardiac morphologic abnormalities in mice deficient for key regulators of the caspase-dependent signaling underscored its role in heart development. However, the mechanisms regulating apoptotic gene expression in the developing heart are unknown. As polypyrimidine tract binding proteins (PTB) determine gene isoform expression during myoblast differentiation and contribute to Apaf-1 translation in cell lines, we investigated whether PTB regulate apoptotic gene expression in differentiating cardiomyocytes. Our results show that PTB are expressed in the embryonic heart and are silenced during development, coinciding with a reduction in the expression of apoptotic genes. Overexpression of PTB in postnatal cardiomyocytes, which express low levels of PTB and apoptotic genes, induced an increase in the amount of pro-apoptotic proteins without affecting abundance of their respective transcripts. Translation of the reporter gene Firefly Luciferase preceded by the 5′-untranslated region of Apaf-1 or Caspase-3 was enhanced by PTB in cardiomyocytes. PTB silencing in fibroblasts induced a decrease of apoptotic protein levels. PTB overexpression in cardiomyocytes induced caspase activity and caspase-dependent DNA fragmentation during ischemia, which is otherwise caspase-independent in differentiated cardiomyocytes. Our results show that PTB contribute to apoptotic gene expression and modulate the susceptibility to caspase activation in differentiating rat cardiomyocytes.Cell Death and Differentiation advance online publication, 10 July 2009; doi:10.1038/cdd.2009.87.

Smad4 is the central intracellular mediator of transforming growth factor-beta (TGF-beta) signaling, which plays crucial roles in tissue regeneration, cell differentiation, embryonic development, and regulation of the immune system. Conventional Smad4 gene knockout results in embryonic lethality, precluding its use in studies of the role of Smad4 in inner ear development. We used chondrocyte-specific Smad4 knockout mice (Smad4(Co/Co)) to investigate the function of Smad4 in inner ear development. Smad4(Co/Co) mice were characterized by a smaller cochlear volume, bone malformation, and abnormalities of the osseous spiral lamina and basilar membrane. The development of the hair cells was also abnormal, as evidenced by the disorganized stereocilia and reduced density of the neuronal processes beneath the hair cells. Auditory function tests revealed the homozygous Smad4(Co/Co) mice suffered from severe sensorineural hearing loss. Our results suggest that Smad4 is required for inner ear development and normal auditory function in mammals. Developmental Dynamics, 2009. (c) 2009 Wiley-Liss, Inc.

We performed a multicentric study to assess the impact of two different culture procedures on the detection of chromosomal abnormalities in 217 consecutive unselected cases with chronic lymphocytic leukemia (CLL) referred for routine analysis either at the time of diagnosis (n = 172) or during disease evolution (n = 45). Parallel cultures of peripheral blood or bone marrow were set up with the addition of either the conventional B-cell mitogen 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or a combination of CpG oligonucleotide (CpG) and interleukin-2 (IL-2). Cytogenetic analyses were performed on both cultures. Clonal abnormalities were identified in 116 cases (53%). In 78 cases (36%), the aberrant clone was detected in both cultures. Among these, the percentages of aberrant metaphases were similar in both conditions in 17 cases, higher in the CpG/IL-2 culture in 43 cases, and higher in the TPA culture in 18 cases. Clonal aberrations were detected in only one culture, either in CpG/IL-2 or TPA in 33 (15%) and 5 (2%) cases, respectively. Taken together, abnormal karyotypes were observed in 51% with CpG/IL-2 and 38% with TPA (P < 0.0001). Application of FISH (n = 201) allowed the detection of abnormalities not visible by conventional cytogenetic analysis in 80 cases: del(13q) (n = 71), del(11q) (n = 5), +12 (n = 2), del(14q) (n = 1), and del(17p) (n = 1). In conclusion, our results confirm that CpG/IL-2 stimulation increases the detection rate of chromosomal abnormalities in CLL compared with TPA and that further improvement can be obtained by FISH. However, neither conventional cytogenetics nor FISH detected all aberrations, demonstrating the complementary nature of these techniques. (c) 2009 Wiley-Liss, Inc.

PURPOSE.: This study was performed to investigate the cause of nonimmune hydrops fetalis by measuring the peak systolic velocity (PSV) in the middle cerebral artery (MCA) and velocity waveforms of the ductus venosus (DV) with Doppler. METHODS.: This cross-sectional study was done on 19 pregnancies referred to three university teaching hospitals for further investigation of nonimmune hydrops fetalis in 2007 and 2008. The MCA-PSV and DV velocity waveforms were recorded in all fetuses. Anemia was investigated in cases with MCA-PSV values greater than 1.50 MoM (multiple of the median). Cardiovascular causes and chromosomal abnormalities were investigated in fetuses with abnormal DV velocity. RESULTS.: Four of 19 fetuses had MCA-PSV values greater than 1.50 MoM. The causes of anemia were cytomegalovirus, parvovirus B19 infections, congenital heart disease, and Turner syndrome. Four cases had reversed flow in the DV; three of them had congenital heart disease on echocardiography; and one had a normal echocardiogram, but an abnormal karyotype was detected. CONCLUSION.: Assessment of the MCA-PSV and DV velocity waveforms during sonographic examination of fetuses with nonimmune hydrops fetalis may improve our knowledge about the etiology of this condition. (c) 2009 Wiley Periodicals, Inc. J Clin Ultrasound, 2009.