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Biomedical subjects

D R Thomas

Publications and source records attributed to D R Thomas.

At least 19 recordsLinked to original sources

m-Chlorophenylpiperazine (mCPP) is an antagonist at the cloned human 5-HT2B receptor.

The behavioural effects of m-chlorophenylpiperazine (mCPP) in rats and its clinical effects in man are thought to be related to its action at 5-HT2B/2C receptors. However, although mCPP is a partial agonist at these subtypes in rat, its efficacy at human 5-HT2B/2C receptors is unknown. We therefore investigated the activity of mCPP at cloned human 5-HT2B and 5-HT2C receptors. mCPP was a partial agonist at the human 5-HT2C receptor but antagonized the human 5-HT2B receptor. Therefore, while supporting the proposal that at least some of the clinical effects of mCPP are likely to be mediated via stimulation of the 5-HT2C receptor, this study also suggests that any 5-HT2B receptor-mediated effects are more likely to result from receptor blockade than from receptor activation.

Animals

Functional effects of the bacterial insecticide Bacillus thuringiensis var. kurstaki on aquatic microbial communities.

Epilithic microbial communities were colonized on leaf disks and exposed to commercial preparations of Bacillus thuringiensis var. kurstaki (Btk) in aquatic microcosms. Responses in terms of microbial respiration, bacterial cell density, protozoan density, and microbial decomposition activity were measured. Test concentrations for treatments with Dipel 64AF and Dipel 8AF in microcosms were the expected environmental concentration (EEC) of 20 IU/ml, 100x the EEC, and 1000x the EEC. Bacterial cell density in the biofilm of leaf disks was significantly increased at concentrations as low as the EEC. There were no concomitant alterations in protozoan density. Microbial respiration was significantly increased, and decomposition activity was significantly decreased, but only at the artificially high concentration of 1000x the EEC. This effect was attributed to the spore-crystal component rather than formulation ingredients. Microbial decomposition of leaf material was also determined in outdoor stream channels treated at concentrations ranging from the EEC to 100x the EEC. Although there tended to be reduced decomposition activity in treated channels, there were no significant differences in mass loss of leaf material between treated and control channels. Various regression, classification, and ordination procedures were applied to the experimental data, and none indicated significant treatment effects. These results from laboratory and controlled field experiments indicate that contamination of watercourses with Btk is unlikely to result in significant adverse effects on microbial community function in terms of detrital decomposition.

Agammaglobulinaemia Tyrosine Kinase

Hospital-acquired pressure ulcers and risk of death.

OBJECTIVE: To evaluate the impact of in-hospital pressure ulcer development on mortality among older, high-risk, hospitalized patients up to 1 year post-hospital discharge, after adjusting for baseline patient characteristics, disease severity, hospital complications, and discharge activity level. DESIGN: A prospective, inception, cohort study. SETTING: An urban, tertiary, acute care, university teaching hospital. PATIENTS: A total of 286 patients aged 55 or older, expected to be confined to bed or chair for at least 5 days, who were admitted to the hospital without a Stage 2 or greater pressure ulcer. MEASUREMENTS: The primary outcome measurement was time to death from admission to 1-year post-hospital discharge. Baseline information included demographic, medical, functional, and nutritional variables known to be associated with increased mortality. Measures of global disease severity and co-morbidity included the admitting physician's estimate of illness severity and life expectancy, the acute physiology score of APACHE II, the Co-morbidity Damage Index, and the Medicus Nursing Classification Score. Baseline infections, incident infections, and noninfectious hospital complications were determined. Functional activity level was determined at hospital discharge. Post-discharge vital status was determined by telephone interviews at 3,6,9, and 12 months after discharge and confirmed by death certificate review. MAIN RESULTS: Development of an in-hospital pressure ulcer was associated with greater risk of death at 1 year (59.5% vs 38.2%, P = .02). However, pressure ulcer development did not remain independently associated with decreased survival after adjusting for other predictors of mortality. Predictors of mortality at hospital admission by multivariate Cox regression analysis included weight loss in the 6 months before admission (RR 2.4, CI 1.6, 3.6), physician estimate of life expectancy (RR 2.1, CI 1.7, 2.6), and the Co-morbidity Damage Index (RR 1.1, CI 1.0, 1.2). Multivariate predictors of 1-year mortality at discharge included physician estimate of life expectancy (RR 2.2, CI 1.8,2.6), weight loss in the 6 months before admission (RR 2.2, CI 1.5,3.2), remaining confined to bed or chair (RR 1.9, CI 1.2,3.1), and the total number of hospital complications (RR 1.3, CI 1.2,1.5). CONCLUSIONS: Pressure ulcers that develop during acute hospitalization are not associated with reduced 1-year survival among high risk older persons after adjusting for nutritional and functional status, global measures of disease severity and co-morbidity, and noninfectious hospital complications.

APACHE

Nutritional factors affecting wound healing.

The consistent relationship between poor nutritional status and risk of complications forms the cornerstone of nutritional support. Yet there is controversy about the ability of nutritional support to reduce complications or improve wound healing. This controversy stems from a number of issues. Diagnosing poor nutrition is not always easy and straight forward. There is sometimes a question whether a patient is malnourished or simply in overall poor health. Studies examining the relationship between nutrition and patient outcome are typically based on animal rather than human models. Even in clinical settings, aspects of care such as enteral or parenteral nutrient delivery may decrease the benefit of nutritional support, making outcomes even harder to measure. The effect of specific nutrients have been examined, such as protein, amino acids, vitamins C and A, and zinc. However, there are still questions regarding how much individual supplementation of a nutrient will positively affect overall outcomes. Although the relationship between specific nutrients and wound healing is not clearly defined by current studies, each patient should be provided with a complete, balanced therapeutic diet. There is at least suggestive evidence that improvement in nutritional status can improve outcomes of wound healing.

Animals

Preoperative assessment of older adults.

Caring for older patients who need surgery presents challenging medical situations. The clinical paradigm involves identifying coexisting disease, defining the urgency of the intervention, and predicting postoperative complications based on the type of surgery planned. The prime function of the medical consultant is searching for correctable medical conditions. The consultant must carefully identify coexisting and comorbid conditions. Emergency surgery should be avoided, if possible, by elective planning. The risk of surgery varies with the procedure. Non-body cavity surgery, with the exception of hip fracture repair, is usually tolerated well. Age is a risk factor for surgery, but coexisting disease is more important than age alone. The net effect of improvements in surgical outcome advances the age at which surgical risk becomes prohibitive.

Age Factors

The risk of acquiring Q fever on farms: a seroepidemiological study.

OBJECTIVES: To determine the occupational risk of Q fever. DESIGN: Cohort study. SETTING: Community: five English local authority districts. SUBJECTS AND METHODS: Prevalence and incidence of immunoglobulin G (IgG) specific antibody to Coxiella burnetii phase II antigen was measured in a representative (study) cohort of farm workers in the United Kingdom, and detailed exposure data were collected. Also seroprevalence of Q fever in a (control) cohort of police and emergency service personnel was measured. RESULTS: Prevalence was significantly (P < 0.01) higher in the study cohort (105/385 v 43/395). During the first 12 month period after enrollment no seroconversions were found (upper 95% confidence limit: 1318/100,000/year). During the second 12 month period after enrollment two seroconversions were found, equalling an incidence of 813/100,000/year (95% confidence interval (95% CI) 98-2937/100,000/year). No association was found between seroprevalence and age. In the study cohort, extent of total contact with farm animals seemed more important than exposure to any specific animal: full time employees were more than four times more likely to be antibody positive than part time employees (P < 0.05). Exposure to cattle, but not sheep, goats, cats, raw milk, and hay (all reported sources of Q fever) was associated with being positive to Coxiella burnetii IgG by univariate analysis but this association was not independent of total farm animal contact. CONCLUSIONS: The risk of Q fever on livestock farms is related to contact with the farm environment rather than any specific animal exposure. The absence of an increasing prevalence with age suggests that exposure may occur as clusters in space and time (outbreaks).

Adolescent

Prevention and rehabilitation of overuse injuries of the elbow.

Rehabilitation from injury and prevention of injury are terms that describe differing aspects of the same challenge. The clinician must be continually aware of the principles of rehabilitation and their order of priority (prevent further damage, restore motion, restore strength, reestablish coordination) while supervising patients' progress toward their goals. If patients are made aware of these principles at an early stage, and taught to take as much responsibility as possible for their own rehabilitative course, they will be more likely to reach their own ideal compromise of safety and speed of progress. In addition to helping with rehabilitation from injury, knowledge and self-awareness that patients obtain during this process may help in the prevention of future injuries.

Cumulative Trauma Disorders

Zoonotic illness--determining risks and measuring effects: association between current animal exposure and a history of illness in a well characterised rural population in the UK.

STUDY OBJECTIVES: To recruit a representative sample of farmworkers, accurately quantify the range and extent of their animal exposures, and measure the associated risks of illness. DESIGN: Inception cohort. SETTING: The study was undertaken among farmworkers living in five local authority areas in the catchment of Hereford and Preston Public Health Laboratories, England. PARTICIPANTS: A quota sample of 404 people on 255 agricultural holdings took part. The holdings were selected at random from the Ministry of Agriculture, Fisheries and Food register. Altogether 58% of eligible subjects approached agreed to participate. MEASUREMENTS AND MAIN RESULTS: The sample had the same sex distribution as the 1991 census for those giving their occupation as agriculture. The mean age was significantly (p < 0.01) higher (44.6 years v 42.2 years) than that of those giving their occupation as agriculture, forestry or fishing in the census, although the modal range (45-59 years) was the same. At enrollment interviews, subjects individually reported contact with up to nine animal species (mode 4) out of 26 reported in all. Based on the numbers contacted and the frequency and intimacy of contact, scores on a ranked ordinal scale from 0-5 were constructed for each species and frequencies for each score were plotted. Subjects also reported past operations and serious illness. A history of pneumonia was significantly (p < 0.05) associated with a pigeon loft on the farm (relative risk (RR) 7.3) and attending farrowing pigs (RR 6.6), and one of leptospirosis with a rat problem on the farm (RR 28.1). Cattle contact was associated with a significantly lower likelihood (protective) of glandular fever (RR 0.19) and rheumatic or scarlet fever (RR 0.12). These effects were significantly related to rankings of the extent of exposure. CONCLUSIONS: It is possible to recruit a representative sample of farmworkers and measure their animal exposures in great detail. Among these exposures, associations with plausible risk factors for pneumonia and leptospirosis and apparently protective factors for glandular fever, scarlet fever, and rheumatic fever have been demonstrated, which further show a relationship between the extent of exposure and response. These findings can be tested further by examining the relationship of exposures to serological evidence of illness or by further prospective follow up of this and similarly well characterised cohorts, or both.

Adult

BRL 46470A: a highly potent, selective and long acting 5-HT3 receptor antagonist with anxiolytic-like properties.

The novel 5-HT3 antagonist, BRL 46470A (endo-N-(8-methyl-8-azabicyclo [3.2.1]oct-3-yl)2,3-dihydro-3,3 dimethyl-indole-1-carboxamide, hydrochloride), has been investigated in a series of in vitro and in vivo tests, including the effect of the drug in models of anxiolysis. In classical tests for 5-HT3 receptor antagonism, BRL 46470A was shown to antagonise 5-HT3 mediated responses in the guinea-pig ileum [pA2 8.3 +/- 0.5, slope 0.98 +/- 0.20, mean +/- SEM (5)], the rabbit isolated heart (pA2 10.1 +/- 0.1, slope 1.2 +/- 0.2, n = 5) and the rat Bezold-Jarisch model (ID50 0.7 microgram/kg IV +/- 0.1, n = 8), with a long duration of action (> 3 h). BRL 46470A selectively displaced [3H]-BRL 43694 from 5-HT3 binding sites in rat brain membranes (Ki 0.32 nM +/- 0.04, n = 4) without displacing (at concentrations greater than 1 microM) a wide variety of ligands binding to other neurotransmitter receptors, opioid receptors and to neurotransmitter gated ion channel complexes. In vivo, BRL 46470A showed anxiolytic-like activity in two animal models predictive of antianxiety effects-elevated X-maze and social interaction in rats. In both models, BRL 46470A showed significant activity over a wide dose-range following both oral (0.0001-0.1 mg/kg PO) and systemic administration. The unique level of potency of BRL 46470A was apparent in the rat social interaction test and was shown to be 100 fold more potent than the 5-HT3 receptor antagonist ondansetron, with no evidence of a bell-shaped dose response curve over 4 orders of magnitude.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

A key to the identification of arrested gastrointestinal nematode larvae of sheep in Britain.

A simple key is presented for the identification of arrested larval nematodes recovered from the gastrointestinal tract of sheep slaughtered in Britain. The parasites included in this key are those species which are most commonly seen to undergo arrested development in sheep. They include Teladorsagia (Ostertagia) spp., Haemonchus contortus, Trichostrongylus axei, intestinal Trichostrongylus spp., Nematodirus battus, Nematodirus filicollis, and Cooperia spp. Easily identifiable morphological features, together with overall dimensions, are used to separate these species.

Animals

Inpatient community-based geriatric assessment reduces subsequent mortality.

OBJECTIVE: To evaluate the effect of an Inpatient Geriatric Consultation Team on patient outcome. DESIGN: Randomized controlled clinical trial. SETTING: A non-academic-affiliated 503-bed community hospital. PATIENTS: All inpatients over the age of 70 years. Sixty-two patients received multidimensional geriatric assessment, and 58 patients received no intervention. INTERVENTION: Team assessment, leading to formal recommendations to the attending physician. MEASUREMENTS: Data were collected on hospital length of stay, referrals to community service, discharge destination, hospital readmissions in 6 months, number of post-discharge physician visits, and change in functional status. Mortality at 6 months and at 1 year was determined for each patient. MAIN RESULTS: At 6 months, 12/58 patients (21%) had died in the control group versus 3/62 (6%) patients in the experimental group (P = 0.01). During hospitalization, the length-of-stay was 10.1 days for the control group versus 9.0 days for the experimental group (P = 0.20). The control group had significantly more readmissions (0.6 per patient vs 0.3 per patient, P = 0.02). A higher number of experimental patients, 22% (13/59), showed improvement in ADL scores compared with 7% (4/46) of control patients, P = 0.07. At one year for all randomized patients, 7/68 (10%) of experimental patients and 13/64 (20%) of control patients had died. CONCLUSIONS: Short-term mortality can be reduced in community inpatient acute hospital settings by comprehensive geriatric consultation teams. Important differences in mortality remain at 1 year of followup. Trends towards improved functional status and fewer hospital readmissions favor the intervention group.

Activities of Daily Living

Improving neglected influenza vaccination among healthcare workers in long-term care.

OBJECTIVE: To increase utilization of influenza vaccination among long-term-care health workers. DESIGN: Before-after intervention study. SETTING: A 300-bed life-care community served by 195 staff employees. INTERVENTION: An educational intervention followed by a Vaccination Fair. MEASUREMENTS: Percent receiving vaccination. A post-intervention survey was used to define staff attitudes towards vaccination. RESULTS: Use of influenza vaccination among staff increased from 8% the previous year to 46% during a Vaccination Fair and to 54% during a similar Fair the next year. CONCLUSIONS: Organized institutional efforts to promote immunization among health-care workers, such as a Vaccination Fair, improves compliance among health-care workers.

Attitude of Health Personnel

Stereoselective interaction of mianserin with 5-HT3 receptors.

The interaction of the enantiomers of mianserin with the 5-HT3 receptor was determined. Using [3H]granisetron binding, (-)-mianserin was more potent than (+)-mianserin (pKi 8.46 and 6.95, respectively). The enantiomers competitively antagonized the depolarizing effect of 5-hydroxytryptamine in the rat vagus nerve preparation (pKapp: (-)-mianserin 8.13, (+)-mianserin 6.58). This stereoselectivity was maintained in-vivo as determined using ex-vivo inhibition of [3H]granisetron binding. Therefore, in contrast to its enantiomeric selectivity for the 5-HT1C and 5-HT2 receptors, where the (+)-isomer is more potent, the enantiomeric selectivity of mianserin for the 5-HT3 receptor was reversed. This differential selectivity of the enantiomers of mianserin may be useful in elucidating its utility in anxiety states.

Animals

Salivary testosterone levels and major depressive illness in men.

Studies of testosterone levels in patients with major depressive illness have produced varying results, plasma levels usually being reported. Saliva levels reflect 'free' plasma testosterone, and a pilot study of 11 men with major depression with melancholia, who underwent a standard dexamethasone suppression test, is described. There were no significant differences in testosterone levels compared with an age-matched control group. In the patient group, pre-dexamethasone levels correlated significantly and negatively with depression ratings on the 21-item Hamilton and the Montgomery and Asberg depression scales, and also with state anxiety measured on the Spielberger scale.

Adult

Performance of Polypay, Coopworth, and crossbred ewes: II. Survival and cumulative lamb and wool production over 4 years.

Six ewe genotypes, generated by mating Coopworth (C), Polypay (P), and Suffolk (S) rams to P and Coopworth-type (Ct) ewes, were exposed to Hampshire rams for spring lambing from 1987 through 1990. Data from 1,013 exposures and 973 resultant lambings were used to analyze reproductive traits and cumulative ewe productivity over 4 yr. Ewe body and fleece weights were also analyzed. Ewes from S sires weaned the heaviest lambs and ewes from P sires weaned the largest number of lambs, resulting in similar total weight of lamb weaned per ewe mated. Coopworth-sired ewes weaned the least total weight of lamb per ewe mated. Ewes weaning twins produced 54% more total litter weight per ewe than those weaning singles. Annual ewe survival averaged 95%, ranging from 93% for S x P and C x P ewes to 97% for P x Ct and C x Ct ewes. When cumulative number and weight of lamb produced was assessed on the basis of all ewes starting the trial, P-sired ewes were highest, followed in order by daughters of S and C sires. Suffolk-sired ewes (67 kg) were 13% heavier than daughters of P rams and 19% heavier than daughters of C rams. Adjustment of lamb production for ewe metabolic body size resulted in C-sired ewes being more efficient than the heavier S-sired ewes. Coopworth-sired ewes produced 32% more wool than ewes sired by the other two breeds. Differences in wool production between ewes weaning one or two lambs were small.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

A comparison of generalization functions and frame of reference effects in different training paradigms.

Six experiments were carried out to compare go/no-go and choice paradigms for studying the effects of intradimensional discrimination training on subsequent measures of stimulus generalization in human subjects. Specifically, the purpose was to compare the two paradigms as means of investigating generalization gradient forms and frame of reference effects. In Experiment 1, the stimulus dimension was visual intensity (brightness); in Experiment 2, it was line orientation (line-angle stimuli). After learning to respond (or to respond "right") to stimulus value (SV) 4 and not to respond (or to respond "left") to SV2 (in Experiment 1) or SV1 (in Experiment 2), the subjects were tested for generalization (recognition) with an asymmetrical set of values ranging from SV1 to SV11. Go/no-go training produced peaked gradients, whereas choice training produced sigmoid gradients. The asymmetrical testing resulted in a gradual shift of the peak of responding (go/no-go group) or in the point of subjective indifference (PSI; choice group) toward the central value of the test series; thus, both paradigms revealed a frame of reference effect. The results were comparable for the quantitative (intensity) and the qualitative (line-angle) stimulus dimensions. Experiment 3 compared the go/no-go procedure with a yes/no procedure in which subjects responded "right" to SV4 and "left" to all other intensities and found no differences between these procedures. Thus the difference in gradient forms in go/no as opposed to (traditional) choice paradigms depends on whether one or two target stimuli are used in training. In Experiment 4, in which visual intensity was used, the shift in the PSI following choice training varied positively with the range of asymmetrical test stimuli employed. In Experiment 5, also with visual intensity, the magnitude of the peak shift following go/no-go training varied as a function of overrepresenting a high or a low stimulus value during generalization testing. Experiment 6, with line angles, showed that the PSI following choice training varies in a similar way. The frame of reference effects obtained in these experiments are consistent with an adaptation-level model.

Discrimination Learning