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Biomedical subjects

R Lewis

Publications and source records attributed to R Lewis.

At least 145 records · Page 8Linked to original sources

Biomarkers and pediatric environmental health.

It is now possible to identify biochemical and/or cellular changes in humans due to exposure to an environmental toxin. These changes are called biomarkers and are currently used in research studies to identify individuals exposed to specific toxic substances. Advances in the field of biomarker technology may have important implications for the detection, prevention, and treatment of certain diseases in children. This technology may enable physicians to screen children who have no clinically detectable illness for evidence of exposure to specific toxins. Such information could lead to implementation of preventive measures and development of new therapeutic strategies. However, several important issues, including potential adverse consequences resulting from the widespread use of this technology, must be considered prior to its utilization within a clinical setting. Leaders of the pediatric and public health communities should recognize the paucity of scientific data in the pediatric environmental health area, and new approaches to this important aspect of child health should be developed. This article will address several of the issues involved in pediatric environmental health and consider questions that should be answered as the potential for technology transfer becomes a reality.

Adult↗

Characterization of the electrophysiological, biochemical and behavioral actions of epibatidine.

Epibatidine has been reported to be a potent, nonopioid analgesic. In this study we further characterized its receptor interactions and its analgesic properties. Radioligand binding assays demonstrated that epibatidine has high affinity for nicotinic receptors (Ki = 0.12 nM) but low affinity for opioid and other receptors (Ki > 3.0 microM). In vitro functional assays demonstrated that the compound is a potent agonist at both neuronal and neuromuscular nicotinic receptors. Epibatidine depolarized rat isolated vagus nerve with an EC50 of 33.1 nM and contracted guinea pig ileum with an EC50 of 6.1 nM. Epibatidine contracted frog rectus abdominis muscle with an EC50 of 18.2 nM. In vivo, epibatidine demonstrated short-lived analgesic actions. Epibatidine (10 and 30 micrograms/kg), at 5 but not 20 min after dosing, increased the threshold for vocalization evoked by foot shock. Epibatidine, at 5 and 20 but not 60 min after dosing, also increased the latency to a nociceptive response in a hot-plate assay. Both (+)- and (-)-enantiomers of epibatidine were active in these assays. The action of epibatidine in the hot-plate test was reversed by the nicotinic receptor antagonist mecamylamine but not by the opioid receptor antagonist naloxone. In contrast to morphine, epibatidine failed to increase locomotor activity. These findings demonstrate that epibatidine is a potent agonist at both neuronal and neuromuscular nicotinic receptors. These findings also demonstrate a short-lived, naloxone-insensitive, analgesic action for both the (+)- and (-)-enantiomers of epibatidine.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesics↗

Factors precluding patients' discharge to the community. A geropsychiatric hospital survey.

Study subjects were the 206 inpatients at a 210-bed university-affiliated, state-operated geropsychiatric hospital in July 1993. Staff psychiatrists, using the behavioral component of the Agitation Behavior Mapping Instrument (ABMI) and a nonbehavioral component added by the authors, determined reasons why their patients could not return to the community at the time of the study. Aggression, nonbehavioral problems, and inability to care for self accounted for three-quarters of the primary reasons precluding immediate community placement. Of these three reasons, aggressive behavior was both the most common and the most correctable factor keeping subjects in the hospital. Aggressive behavior occurred most commonly among psychotic patients, intermediate among demented patients and least commonly among patients with mood disorders. The authors suggest the need to better define those aggressive behaviors and to develop effective treatments that can be transported with patients as they return to the community.

Activities of Daily Living↗

Multiwire Gas Proportional Counters: Decrepit Antiques or ClassicPerformers?

An overview of the operational characteristics of multiwire gas proportional counters is given with particular reference to their use in X-ray diffraction. Their strengths and weaknesses are analysed and it is demonstrated that these devices are able to offer a combination of features that is unique. Some examples of synchrotron radiation experiments performed with gas detectors are used to illustrate their performance, and finally, the current status of development and prospects for the future development of gas detectors are reviewed.

Journal Article↗

Clinical evaluation of induction immunosuppression with a murine IgG2b monoclonal antibody (BMA 031) directed toward the human alpha/beta-T cell receptor.

Mouse mAbs directed against the alpha/beta-TCR were tested in clinical phase II and in triple-blind, randomized phase III studies. A clinical phase II trial administered 50 mg of murine anti-human alpha/beta-TCR mAb (BMA 031) intravenously on the day of, as well as 2 and 4 days after, cadaveric donor renal transplantation in combination with a CsA/prednisone regimen. None of 12 patients showed even moderately adverse side effects. A phase III, triple-blind randomized trial enrolled 24 patients in the BMA 031 group and 22 patients in a placebo control group. BMA 031 treatment significantly reduced the incidence of rejection events within the first 10 posttransplant days to 1 patient versus 9 episodes in the placebo group (P < 0.01). By the end of 30 days, 6 rejection episodes had occurred in the BMA 031 group and 11 in the control cohort (P = NS). After a minimum of 30 months follow-up, the actual allograft survival rate was 87% in the BMA-treated group compared with 68% in the control cohort.

Animals↗

The structure of an immunodominant loop on foot and mouth disease virus, serotype O1, determined under reducing conditions.

Residues 136-159 of VPI of foot and mouth disease virus (FMDV) comprise the G-H loop of the protein and form a prominent feature on the surface of virus particles. This sequence contains an immunodominant neutralizing epitope, which can be mimicked with synthetic peptides, and includes an Arg, Gly, Asp motif which has been implicated in the binding of the virus to cellular receptors. Crystallographic analysis of native virus particles failed to resolve the structure of this region due to its disordered state. However, reduction of a disulphide bond between cysteine residues 134 of VP1 and 130 of VP2 caused the G-H loop to collapse onto the surface of the virus particle and allowed its conformation to be determined.

Amino Acid Sequence↗

The impaired driver: hospital and police detection of alcohol and other drugs of abuse in motor vehicle crashes.

STUDY OBJECTIVES: To determine the incidence of drugs of abuse and alcohol use in admitted drivers involved in motor vehicle crashes (MVCs) and to determine the rate of police detection of alcohol and drug use in these motorists. DESIGN: Retrospective chart review of hospitalized drivers involved in MVCs and review of corresponding police reports. SETTING: Two Level I trauma centers in a large metropolitan region. PARTICIPANTS: All MVC drivers/motorcycle operators admitted to the trauma service from January 1, 1990, to December 31, 1990. MEASUREMENTS AND MAIN RESULTS: The records of 634 injured motorists were reviewed; 200 (32% of the 625 patients with serum alcohol levels) were legally drunk (serum alcohol of 100 mg/dL or more), and 132 (22.6% of the 585 urine drug screens) had positive urine drug screens. Cocaine was the most prevalent drug of abuse, present in 51 patients (8.7%). Two hundred eighty-five patients (45.0%) were considered impaired (alcohol of 100 mg/dL or more and/or positive drug screen), representing almost half of all motorists admitted. The impaired motorists were younger, more often male, less likely to use a seat belt or helmet, and had higher Injury Severity Scores than their unimpaired counterparts. Police reports were available for 446 patients, 139 (31.2%) of whom were legally drunk and 67 (15%) of whom had positive drug screens, yielding an overall impairment rate of 46.2%. Only 34 (16.5%) patients were cited for driving under the influence. CONCLUSION: An exceedingly high rate of impairment existed in this population of seriously injured motorists in a metropolitan region, the majority of whom were not charged by the police. Although alcohol is the most prevalent source of driver impairment, other drugs of abuse are also important contributors to this problem.

Accidents, Traffic↗

Cancer and noncancer risk to women in agriculture and pest control: the Agricultural Health Study.

The Agricultural Health Study is a collaborative effort involving the National Cancer Institute, the US Environmental Protection Agency, and the National Institute of Environmental Health Sciences. A goal of this investigation is to establish a large cohort of men and women that can be followed prospectively for 10 years or more to evaluate the role of agricultural exposures in the development of cancer, neurologic disease, reproductive difficulties, childhood developmental problems, and other chronic diseases. The study also will provide an opportunity to assess the role that diet, cooking methods, and other lifestyle factors have on the cause of cancer and other diseases. The cohort will be composed of approximately 112,000 adult study subjects, including 42,000 women, making this one of the largest cohorts of women ever assembled for an epidemiologic investigation of environmental and occupational exposures. Children of farm families also will be enrolled. The study will be conducted in Iowa and North Carolina. Enrollment will begin in December 1993 and continue for 3 years.

Adult↗

A componential model of human interaction with graphs: 1. Linear regression modeling.

Task analyses served as the basis for developing the Mixed Arithmetic-Perceptual (MA-P) model, which proposes (1) that people interacting with common graphs to answer common questions apply a set of component processes--searching for indicators, encoding the value of indicators, performing arithmetic operations on the values, making spatial comparisons among the indicators, and responding; and (2) that the type of graph and user's task determine the combination and order of the components applied (i.e., the processing steps). Two experiments investigated the prediction that response time will be linearly related to the number of processing steps according to the MA-P model. Subjects used line graphs, scatter plots, and stacked bar graphs to answer comparison questions and questions requiring arithmetic calculations. A one-parameter version of the model (with equal weights for all components) and a two-parameter version (with different weights for arithmetic and nonarithmetic processes) accounted for 76%-85% of individual subjects' variance in response time and 61%-68% of the variance taken across all subjects. The discussion addresses possible modifications in the MA-P model, alternative models, and design implications from the MA-P model.

Computer Graphics↗

Placental lactogen binding sites in the pregnant rabbit choroid plexus.

Prolactin has direct effects on the CNS. The highest concentration of prolactin receptors resides within the choroid plexus where they probably function to transport prolactin from blood into CSF. Another member of the lactogen family of hormones, placental lactogen (PL), also affects CNS activity and may similarly employ the cerebroventricular system as an intermediary. In order to determine whether the choroid plexus was a PL target tissue, in vitro autoradiography was used to identify specific PL binding sites in the choroid plexus of pregnant New Zealand White rabbits. Frozen brain sections were incubated in a medium containing 125I human PL (hPL) alone (total binding) or with a 500-fold excess of unlabelled hPL (nonspecific binding). The specificity of the binding was assessed with unlabelled human growth hormone (hGH) and ovine luteinising hormone (oLH). An intense autoradiographic reaction occurred over the choroid plexus of tissue sections incubated with 125I hPL alone. Excess unlabelled hPL and hGH, which is lactogenic in the rabbit, caused a significant reduction (P < 0.001) in the binding of radiolabelled hPL to the choroid plexus. In contrast, unlabelled oLH had no effect on radiolabelled hPL binding to this tissue. The results support a role for the choroid plexus in the interactions between PL and the CNS.

Animals↗