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Biomedical subjects

M G Smith

Publications and source records attributed to M G Smith.

At least 37 records · Page 2Linked to original sources

Identifying anxiety disorders in adolescents hospitalized for alcohol abuse or dependence.

In structured clinical interviews of 43 adolescents hospitalized for alcohol abuse or dependence, 17 subjects met criteria for an anxiety disorder, with social phobia (N = 9) and posttraumatic stress disorder (N = 7) most common. Of these 17 subjects, only four were identified in hospital records as having an anxiety disorder. In a comparison of 30 hospitalized adolescents with a matched control group of 30 adolescents from the community, the hospitalized adolescents had a higher rate of anxiety disorders, psychoactive substance use disorders, disruptive behavior disorders, and mood disorders.

Adolescent↗

GM1 ganglioside treatment partially reverses the nigrostriatal dopamine defect in the weaver mutant mouse.

The weaver mutation in the mouse is a developmental disorder characterized by cerebellar atrophy as well as decreased numbers of substantia nigra dopaminergic neurons and a striatal dopamine loss. Since the nigrostriatal dopamine loss occurs postnatally, the present study was performed to determine whether early intervention with GM1 ganglioside could alter the extent of this dopamine loss. Weaver mice that received injections of GM1 ganglioside (30 mg/kg) daily, beginning at 7-10 days of age, had significantly higher striatal dopamine levels and significantly more tyrosine hydroxylase-positive substantia nigra pars compacta neurons than weaver mice that received only daily saline injections. These results show that GM1 treatment can alter at least some aspects of this inherited developmental disorder. If the weaver defect is related to a deprivation of trophic support for certain midbrain dopaminergic neurons, the presence of GM1 may be able to enhance the survival of these neurons.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Yeast mitochondria contain ATP-sensitive, reversible actin-binding activity.

Sedimentation assays were used to demonstrate and characterize binding of isolated yeast mitochondria to phalloidin-stabilized yeast F-actin. These actin-mitochondrial interactions are ATP sensitive, saturable, reversible, and do not depend upon mitochondrial membrane potential. Protease digestion of mitochondrial outer membrane proteins or saturation of myosin-binding sites on F-actin with the S1 subfragment of skeletal myosin block binding. These observations indicate that a protein (or proteins) on the mitochondrial surface mediates ATP-sensitive, reversible binding of mitochondria to the lateral surface of microfilaments. Actin copurifies with mitochondria during subcellular fractionation and is released from the organelle upon treatment with ATP. Thus, actin-mitochondrial interactions resembling those observed in vitro may also exist in intact yeast cells. Finally, a yeast mutant bearing a temperature-sensitive mutation in the actin-encoding ACT1 gene (act1-3) displays temperature-dependent defects in transfer of mitochondria from mother cells to newly developed buds during yeast cell mitosis.

Actins↗

Panic in otolaryngology patients presenting with dizziness or hearing loss.

This study compared 50 patients presenting to an otolaryngology clinic with a complaint of dizziness and 50 patients presenting with hearing loss on questionnaire measures of panic, phobic avoidance, generalized anxiety, and depression. Clinical and laboratory evaluations of vestibular and audiological complaints were also completed. Twenty percent of the group with dizziness and none of the group with hearing loss reported symptoms that met DSM-III-R criteria for panic disorder. Patients with dizziness and peripheral vestibulopathy had more symptoms of phobic avoidance, generalized anxiety, and depression than patients with confirmed hearing loss.

Adult↗

Some comments on potency measures in mutagenicity research.

In this article, the measurement of the potency of a chemical or mixture from its dose response in a particular assay is addressed. Attention is focused on data from the Ames Salmonella assay. Three measures of potency are explored and shown to be highly correlated. The presentation then discusses specific areas of research that might benefit from a study of potency.

Dose-Response Relationship, Drug↗

Targeted integration of transfected and infected adeno-associated virus vectors containing the neomycin resistance gene.

Human adeno-associated virus (AAV) integrates specifically into a site (AAVS1) on chromosome 19q13.3-qter. We report that both transfected and infected AAV-vectors will target a foreign gene preferentially to AAVS1. Of 11 infected cell lines studied, nine (82%) showed integration of the neomycin resistance marker into AAVS1, which confirms the findings of previous investigations. We also show site-specific integration (nine out of 12 cell lines, 75%) following transfection of an AAV vector containing the neomycin gene. The ability of transfected AAV sequences to preferentially target and express selectable genes at a known site in the human genome extends the potential use of AAV as a vector in gene therapy.

Anti-Bacterial Agents↗

Absence of HIV transmission from an infected orthopedic surgeon. A 13-year look-back study.

OBJECTIVE: To determine the risk of human immunodeficiency virus (HIV) transmission from an HIV-infected orthopedic surgeon to patients undergoing invasive procedures. DESIGN: Retrospective epidemiologic follow-up study. PARTICIPANTS: A total of 2317 former patients on whom the orthopedic surgeon performed invasive procedures between January 1, 1978, and June 30, 1991 [corrected]. MAIN OUTCOME MEASURES: HIV infection or death from an acquired immunodeficiency syndrome (AIDS)-defining tumor or opportunistic infection. RESULTS: An orthopedic surgeon voluntarily withdrew from practice after testing positive for HIV. Testing for HIV was performed on 1174 former patients, representing 50.7% of patients on whom the orthopedic surgeon performed invasive procedures during the 13.5-year period. Patients were tested from each year and from each category of invasive procedure. All patients were HIV-negative by enzyme-linked immunosorbent assay. Two former patients reported known HIV infection prior to surgery. Review of AIDS case registries and vital records failed to detect cases of HIV infection among former surgical patients. The estimated cost of the initial patient notification and testing was $158,500. The patient notification and testing were conducted while maintaining the confidentiality of the orthopedic surgeon who was an active participant in the planning and execution of the study. CONCLUSIONS: The risk of HIV transmission from an HIV-infected surgeon who adheres to recommended infection control practices is extremely low. Notification and HIV testing of former patients in this setting is both disruptive and expensive and is not routinely recommended.

AIDS Serodiagnosis↗

The prevalence of congenital cervical spinal stenosis in 262 college and high school football players.

Pavlov's ratio is a commonly utilized method for evaluating athletes for cervical stenosis. We evaluated the lateral cervical spine film and determined Pavlov's ratio for 262 college and high school football players. Twenty (7.6%) of these athletes had radiographic evidence of congenital cervical stenosis according to this method. The condition may be more common than expected.

Adolescent↗

Recovery from experimental parkinsonism in primates with GM1 ganglioside treatment.

A parkinsonian syndrome can be produced in nonhuman primates by administration of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Parkinsonian-like symptoms induced acutely by MPTP were ameliorated after treatment with GM1 ganglioside, a substance shown to have neurotrophic effects on the damaged dopamine system in rodents. Treatment with GM1 ganglioside also increased striatal dopamine and metabolite levels and enhanced the dopaminergic innervation of the striatum as demonstrated by tyrosine hydroxylase immunohistochemistry. These results suggest that GM1 ganglioside may hold promise as a therapeutic agent for the treatment of Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Contributions to the design and statistical analysis of in vivo SCE experiments.

Two issues that arise in the design and statistical analysis of in vivo SCE and similar experiments are considered. First, with regard to analysis, the merits of various methods of data transformation are explored in depth. The conclusion drawn is that common transformations of the type studied here seemingly offer little advantage in the assessment of whether a test agent induces SCE in a dose-related manner. Second, a proposal is made for a method to determine, subject to budgetary constraints, the desired numbers of animals/dose group and cells scored/animal. The approach advocated also lends itself to discussions weighing the gains and losses from possible reductions in the number of animals below the 'desired' levels.

Analysis of Variance↗

Destruction of bacteria on fresh meat by hot water.

Strains of different bacterial genera; Escherichia coli (7), Salmonella serotypes (7), Enteropathogenic E. coli O 157 (2), Aeromonas hydrophila (4), Yersinia enterocolytica (1), Pseudomonas fragi (5), and Listeria monocytogenes (5), inoculated onto the surface tissues of pieces of fresh beef were found to be susceptible to the lethal action of hot water. On average, more than 3 log10 (99.9%) of these organisms were destroyed when water at 80 degrees C was applied for 10 or 20 s. Therefore, a hot water decontamination cabinet would be effective for destroying in situ any viable cells of these bacteria which might be present on the surface tissues of fresh beef carcasses.

Animals↗

Development of microcomputer-based mental acuity tests.

Recent disasters have focused attention on performance problems due to the use of alcohol and controlled substances in the workplace. Environmental stressors such as thermal extremes, mixed gases, noise, motion, and vibration also have adverse effects on human performance and operator efficiency. However, the lack of a standardized, sensitive, human performance assessment battery has probably delayed the systematic study of the deleterious effects of various toxic chemicals and drugs at home and in the workplace. The collective goal of the research reported here is the development of a menu of tests embedded in a coherent package of hardware and software that may be useful in repeated-measures studies of a broad range of agents that can degrade human performance. A menu of 40 tests from the Automated Performance Test System (APTS) is described, and the series of interlocking studies supporting its development is reviewed. The APTS tests, which run on several versions of laptop portables and desktop personal computers, have been shown to be stable, reliable, and factorially rich, and to have predictive validities with holistic measures of intelligence and simulator performances. In addition, sensitivity studies have been conducted in which performance changes due to stressors, agents, and treatments were demonstrated. We believe that tests like those described here have prospective use as an adjunct to urine testing for the screening for performance loss of individuals who are granted access to workplaces and stations that impact public safety.

Alcoholic Intoxication↗

Transarticular fixation for severely displaced supracondylar fractures in children.

We have reviewed 34 children who had been treated by open reduction through a medial incision and transarticular pinning for a severely displaced supracondylar fracture of the humerus. Follow-up ranging from nine months to 20 years showed that 27 of 34 elbows (79%) had excellent or good results, with satisfactory resolution of neurovascular problems and no complications due to the method of treatment.

Bone Nails↗

Lipid mediators of tumor necrosis factor-alpha-induced uveitis.

The authors tested the hypothesis that platelet-activating factor (PAF) and cyclooxygenase metabolites of arachidonic acid mediate the ocular inflammatory response to intravitreally injected tumor necrosis factor-alpha (TNF alpha). Rabbits were treated with the PAF receptor antagonist SRI 63-441, the cyclooxygenase inhibitors indomethacin and naproxen, or SRI 63-441 and indomethacin. At 24 hr after intravitreal injection of TNF (20,000 U), the severity of inflammation was assessed based on iridal hypermia, aqueous humor leukocyte number and aqueous humor protein, immunoreactive-prostaglandin E (I-PGE), and leukotriene B4 (LTB4) concentrations. Although all of the treatments significantly reduced the severity of anterior uveitis, SRI 63-441 plus indomethacin was the most effective, indomethacin and naproxen were intermediately effective, and SRI 63-441 was the least effective. The results of this study are consistent with an important role for cyclooxygenase metabolites of arachidonic acid in the inflammatory response to TNF alpha, particularly with respect to dilation of iridal blood vessels. Although naproxen was nearly as effective as indomethacin in reducing aqueous humor I-PGE levels, indomethacin conferred significantly more protection to the blood-aqueous barrier as shown by lower protein levels in the aqueous humor. Thus, although cyclooxygenase inhibition may partially explain the protection afforded the blood-aqueous barrier by these nonsteroidal anti-inflammatory agents, the data suggest that indomethacin may also exert anti-inflammatory effects that are independent of cyclooxygenase inhibition. Furthermore, the data are consistent with TNF alpha releasing PAF in the eye and PAF acting both directly, by increasing vascular permeability, and indirectly, by promoting release of cyclooxygenase and lipoxygenase metabolites of arachidonic acid.

Animals↗

Defeat-induced hypoalgesia in the rat: effects of conditioned odors, naltrexone, and extinction.

In Experiment 1, male rats were either defeated as a colony intruder by alpha conspecifics or had no defeat experience, and 24 hr later they were given a paw injection of formalin prior to observational tests with or without alpha-colony odors. The combination of defeat and tests with these odors produced conditioned hypoalgesia (i.e., a suppression in paw licking) and freezing. In Experiment 2, defeated rats were given either an injection of naltrexone or saline prior to defeat and 24 hr later prior to testing. An injection of naltrexone prior to defeat increased freezing during defeat and later testing. In contrast, naltrexone during testing did not affect freezing but significantly reduced hypoalgesia. In Experiment 3, a 12-hr exposure session with alpha-colony odors extinguished hypoalgesia in previously defeated rats. These findings are discussed in terms of associative, opioid/nonopioid, and adaptive evolutionary processes.

Animals↗

Cognitive performance deficits in a simulated climb of Mount Everest: Operation Everest II.

Cognitive function at simulated altitude was investigated in a repeated-measures, within-subject study of performance by seven volunteers in a hypobaric chamber, in which atmospheric pressure was systematically lowered over a period of 40 d to finally reach a pressure equivalent to 8,845 m, the approximate height of Mount Everest. The portable cognitive test battery used, Automated Performance Test System (APTS), was specifically designed for field research under adverse environmental conditions as evidenced by compact computer design; automated test administrations, data storage, and retrieval; psychometric properties of stability and reliability; and factorial richness. Significant impairments of cognitive function were seen for three of the five tests in the battery; on two tests, grammatical reasoning and pattern comparison, every subject showed a substantial decrement. The results are discussed in terms of the impact of altitude on specific aspects of cognitive function and the importance of having sensitive and reliable instruments to monitor such effects.

Adult↗