Does gastro-oesophageal reflux following PEG placement in stroke patients predict a poorer outcome?
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Biomedical subjects
Publications and source records attributed to Lynne Smith.
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OBJECTIVES: Methamphetamine use is a continuing problem in several regions of the United States and yet few studies have focused on prenatal methamphetamine exposure. The purpose of this study was to estimate the prevalence and correlates of alcohol, tobacco, and other substance use-including methamphetamine-during pregnancy. METHODS: The sample consisted of the first 1632 eligible mothers who consented to participate in a large-scale multisite study focused on prenatal methamphetamine exposure. This unselected screening sample included both users and nonusers of alcohol, tobacco, methamphetamine, and other drugs. Substance use was determined by maternal self-report and/or GC/MS confirmation of a positive meconium screen. RESULTS: Overall, 5.2% of women used methamphetamine at some point during their pregnancy. One quarter of the sample smoked tobacco, 22.8% drank alcohol, 6.0% used marijuana, and 1.3% used barbiturates prenatally. Less than 1% of the sample used heroin, benzodiazepines, and hallucinogens. Multivariate modeling results showed that tobacco smokers and illicit drug users were more likely to be single and less educated, have attended less than 11 prenatal visits, and utilize public financial assistance. CONCLUSIONS: This is the first large-scale investigation to report the prevalence of methamphetamine use during pregnancy in areas of the United States where methamphetamine is a notable concern. Follow-up research is ongoing to investigate the outcomes associated with prenatal methamphetamine exposure. Given that this research extends and confirms previous findings showing that high-risk groups of pregnant women can be identified on the basis of basic demographic characteristics, targeted interventions are greatly needed to reduce serious adverse outcomes associated with prenatal alcohol and tobacco use.
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The aim of this study was to examine submaximal isometric force production guided by perceptual feelings of exertion. Thirty young adults performed isometric knee extensions on an isokinetic dynamometer. Subjects performed five different tests; the first test was the same for all subjects (standard naïve test). During the standard naïve test, subjects were asked to randomly produce force at perceived contraction intensities (25%, 50% and 75% of their maximum voluntary contraction (MVC)), with 100% MVC performed as the final intensity. All intensities, including the 100% MVC, were randomly performed in the other four tests (control tests 1 and 2, post 20% MVC and post 100% MVC tests). Post 20% MVC and post 100% MVC tests included fatiguing isometric exercise at 20% and 100% MVC respectively, which were performed prior to the test protocol. Results show that absolute peak force increased with increasing intensity (P<0.001) during all tests. During the standard naïve test, absolute peak force at 25% and 50% MVC was significantly lower (P=0.009) compared to control test 2, post 20% MVC and 100% MVC tests, and relative peak force was lower at all intensities compared to all other tests (P<0.001). Absolute and relative peak force was most accurate at 50% MVC (-12.06 N and -2.42%, respectively). Prior fatiguing isometric exercise did not affect the subsequent perceptual response range. In conclusion, isometric force was most accurate at 25% MVC but under-produced (perceptually overestimated) during higher contraction intensities preceding a maximal voluntary contraction (100% MVC). The ability to match absolute force with target contraction intensities was most accurate at 50% MVC during all five experimental conditions and poor at opposite ends of the force domain. Furthermore, prior fatiguing isometric exercise did not have an effect on the subsequent perceptual response range.
GPCRs are one of the most popular classes of therapeutic drug targets. It is therefore important to design specific assay formats to readily identify ligands at these receptors. CypHer 5 technology utilizes the general ability of GPCRs to be internalized into the endosomal pathway of a cell in response to agonist ligands. The CypHer 5 dye is fluorescent in acidic environments, but nonfluorescent at neutral pH. When CypHer 5 is bound to a receptor on the extracellular surface of the cell, it is essentially nonfluorescent. On internalization into a cell, it displays a significant increase in fluorescence. Here we demonstrate the detection of agonist activation of two GPCRs in stably transfected live cells using CypHer 5 technology. The G(q)-coupled TRHR-1 and the G(s)-coupled beta(2)-adrenoceptor were both N-terminally tagged with VSV-G. Following addition of CypHer 5-labeled anti-VSV-G antibodies to HEK 293 cells stably expressing the beta(2)-adrenoceptor or CHO-K1 cells stably expressing the TRHR-1, the cells were treated with agonists and then imaged on Amersham Biosciences' IN Cell Analyzer 3000. Data were quantified using a granularity analysis module. Concentration-response curves were obtained with signal-to-background ratios of 7:1 for both receptors. An EC(50) of 0.52 nM was observed on TRH stimulation of the TRHR-1, and an EC(50) of 30 nM was obtained on isoprenaline stimulation of the beta(2)-adrenoceptor. These results demonstrated that the CypHer technology was capable of measuring high-potency agonist responses. The beta(2)-adrenoceptor antagonist, alprenolol, competed for isoprenaline with an IC(50) of 30 nM, indicating that a high-potency antagonist inhibition curve could also be observed using CypHer. CypHer 5 provides a generic tool to measure GPCR activation in a live cell, homogeneous assay format, and may be equally suitable for detecting activation of other classes of cell surface receptors.
To determine fetal growth and the incidence of withdrawal symptoms in term infants exposed to methamphetamine in utero, we retrospectively identified neonates whose mothers used methamphetamine during pregnancy and matched them to unexposed newborns. Exclusion criteria included multiple and preterm gestations. Although there were no differences in infant growth parameters between the methamphetamine-exposed and methamphetamine-unexposed neonates, methamphetamine exposure throughout gestation was associated with decreased growth relative to infants exposed only for the first two trimesters. In addition, there were significantly more small for gestational age infants in the methamphetamine group compared with the unexposed group. Methamphetamine-exposed infants whose mothers smoked had significantly decreased growth relative to infants exposed to methamphetamine alone. Withdrawal symptoms (as determined by a previously reported scoring system) requiring pharmacologic intervention were observed in 4% of methamphetamine-exposed infants. These preliminary findings indicate that methamphetamine use is associated with growth restriction in infants born at term.