Biomedical subjects

R Thompson

Publications and source records attributed to R Thompson.

At least 91 records · Page 5Linked to original sources

PubMed1996

Cloning and characterization of multiple opioid receptors.

Over the course of 1 to 2 years, the field has moved swiftly to investigate the functional and structural properties of the newly cloned opioid receptors. Achieving a better understanding of these macromolecules is likely to have profound implications for drug design aimed at the production of better analgesic drugs, for a more fundamental understanding of mechanisms of action of drugs of abuse, and for a more comprehensive knowledge base regarding the biology of opioid peptides in particular, and neuroactive peptides in general.

Animals↗

PubMed1996

Surgical repair of pressure ulcers.

A team approach is required for the surgical management of the spinal cord-injured patient with a pressure ulcer, beginning preoperatively with patient selection and preparation, continuing through wound debridement and flap closure, and progressing to rehabilitation and patient education. Although possible surgical complications are numerous and the recurrence rate is relatively high, the surgical management of patients with pressure ulcers can be very rewarding. Goals for surgical closure of pressure ulcers include reduction of protein loss through the wound, reduction of rehabilitation costs, prevention of progressive osteomyelitis, and improvement of patient hygiene. The ultimate reward is the restoration of patients to the rehabilitated sitting position so that they can enjoy productive and happy lives.

Humans↗

PubMed1995

Site-directed mutagenesis of varicella-zoster virus thymidylate synthase. Analysis of two highly conserved regions of the enzyme.

We have constructed a series of mutants to study the role of two structurally and functionally important regions of thymidylate synthase (TS) from varicella-zoster virus (VZV). The first centres on a conserved glycine residue in the beta-kink of beta-strand i, a partially buried region of the protein that is important for dimer interactions and the formation of the active site. We show that the glycine residue located in beta-strand i is not essential for enzyme activity and that beta-strand i can readily accommodate several amino acid substitutions and also an insertion. A covariant residue that accommodates these changes was also identified. The second region of interest was the solvent-exposed and highly mobile C-terminal residue which is an essential component of the active site in TS from Lactobacillus casei and Escherichia coli. We demonstrate that removal of the C-terminal residue from VZV TS does not completely inactivate the enzyme, implying that there are significant structural differences between the virus and bacterial enzymes. By combining site-directed mutagenesis and molecular modelling we have identified these differences and propose a model that explains the contrasting activities.

Base Sequence↗

PubMed1995

Rates of change of genetic parameters of body weight in selected mouse lines.

A method based on the animal model is described which allows the estimation of continuous changes in variance components over time using restricted maximum likelihood (REML). The method was applied to the analysis of a selection experiment in which a foundation population formed from a cross between two inbred strains of mice (C57BL/6J and DBA/2J) was divergently selected for 6 week body weight over 20 generations. The analysis suggested that there was an increase in phenotypic variance of about 50% in the low selected lines over the course of the experiment which was attributed to increases in the environmental and additive variance components. Variance changes in the High selected lines were generally smaller than in the Low lines, although there was an estimated 20% increase in the environmental variance. Simple models to explain these effects involving dominance, linkage and epistasis were explored. Testing which of these was responsible for the variance changes noted in this experiment (if any) is difficult, although the epistasis and dominance models require less stringent conditions than the linkage model, and the dominance model is supported by evidence of heterosis in the F1.

Analysis of Variance↗

PubMed1995

Using marker-maps in marker-assisted selection.

A method of using information on the location of markers to improve the efficiency of marker-assisted selection (MAS) in a population produced by a cross between two inbred lines is developed. The method is closer to mapping QTL than the selection index approaches to MAS described by previous authors. We use computer simulations to compare our method with phenotypic selection and two selection index approaches, simulations being performed on three genetic maps. The simulations show that whilst MAS can be considerably more efficient than phenotypic selection differences between the three MAS methods are slight. Which of the MAS methods is best depends on a number of factors: in particular the genetic map, the time scale under consideration ant the population size are of importance.

Chromosome Mapping↗

PubMed1995

Genistein suppresses mammary cancer in rats.

Female Sprague-Dawley CD rats were injected s.c. with 5 mg genistein, a soy phytoestrogen, or 20 microliters of the vehicle, dimethylsulfoxide (DMSO), on days 2,4 and 6 postpartum. At day 50, they were exposed to 80 micrograms dimethylbenz[a]anthracene (DMBA)/g body wt. Animals treated neonatally with genistein as compared to DMSO had increased latency and reduced incidence and multiplicity of DMBA-induced mammary adenocarcinomas. Mammary whole mount analysis showed that 50 day old female rats treated neonatally with genistein had fewer terminal end buds. Cell proliferation studies revealed that 50 day old genistein-treated rats had lower percentages and total numbers of cells in the S-phase of the cell cycle in terminal end buds, terminal ducts, lobules I and lobules II. In genistein-treated as compared to vehicle-treated female rats, vaginal openings occurred earlier, the estrus cycle was disrupted and the uterine-ovarian weights were smaller. In 50 day old genistein-treated females there were atretic antral follicles, fewer corpora lutea, and lower circulating progesterone but not estradiol-17 beta concentrations. In 21 day old rats treated neonatally with genistein, mammary glands were larger and there were more terminal end buds and terminal ducts, and more proliferative activity in all terminal ductals structures. It appears that neonatal genistein-treatment exerted its chemoprevention action by acting directly to enhance maturation of terminal ductal structures and by altering the endocrine system to reduce cell proliferation in the mammary gland.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1995

Where there is no family doctor: the development of family practice around the world.

Family physicians are generalists trained at the postgraduate level to address the majority of primary care needs of patients of all ages in communities they serve. Throughout the world there is a need for family physicians to serve as cornerstones of comprehensive health care systems that provide high-quality, cost-effective medical and public health services to the entire population. To meet this need, each country must value and adequately finance essential medical and public health services and must provide family physicians with a thorough education focused on the relevant health care problems of the population being served. The authors present an overview of the status of this training throughout the world, outline challenges to the development of such training, and suggest strategies for successful development accompanied by illustrative case studies from South Korea, Venezuela, and Pakistan.

Education, Medical↗

PubMed1995

Exclusion of the locus for autosomal recessive pseudohypoaldosteronism type 1 from the mineralocorticoid receptor gene region on human chromosome 4q by linkage analysis.

Pseudohypoaldosteronism type 1 (PHA1) is an uncommon inherited disorder characterized by salt-wasting in infancy arising from target organ unresponsiveness to mineralocorticoids. Clinical expression of the disease varies from severely affected infants who may die to apparently asymptomatic individuals. Inheritance is Mendelian and may be either autosomal dominant or autosomal recessive. A defect in the mineralocorticoid receptor has been implicated as a likely cause of PHA1. The gene for human mineralocorticoid receptor (MLR) has been cloned and physically mapped to human chromosome 4q31.1-31.2. The etiological role of MLR in autosomal recessive PHA1 was investigated by performing linkage analysis between PHA1 and three simple sequence length polymorphisms (D4S192, D4S1548, and D4S413) on chromosome 4q in 10 consanguineous families. Linkage analysis was carried out assuming autosomal recessive inheritance with full penetrance and zero phenocopy rate using the MLINK program for two-point analysis and the HOMOZ program for multipoint analysis. Lod scores of less than -2 were obtained over the whole region from D4S192 to D4S413 encompassing MLR. This provdes evidence against MLR as the site of mutations causing PHA1 in the majority of autosomal recessive families.

Alleles↗

PubMed1995

A study of the clinical outcome of patients with profound mental retardation gradually withdrawn from chronic neuroleptic medication.

In a naturalistic study of 23 severely and profoundly mentally retarded adult male patients undergoing slow "diagnostic" neuroleptic taper, it was determined that at least 60% could eventually be managed without psychoactive medication. However, many of these demonstrated a remarkably long, but nonetheless transient, period of worsening. This suggests that behavioral deterioration during drug reduction trials does not always indicate a need for chronic neuroleptic maintenance since these behaviors may return to baseline without pharmacological intervention. On the other hand, 40% demonstrated persistent (> 2 years) behavioral worsening. Those individuals who demonstrated persistent deterioration had been generally well controlled on neuroleptics, were somewhat older, and were receiving a higher baseline dose. Most of these persistently worsened subjects currently require some type of psychoactive medication (although only two have been returned to neuroleptics).

Adult↗

PubMed1995

Specific and nonspecific responses to Plasmodium falciparum blood-stage parasites and observations on the gametocytemia in schoolchildren living in a malaria-endemic area of Mozambique.

We have observed specific and nonspecific reactivities to the asexual states and gametocytes of Plasmodium falciparum and examined the effect of chloroquine and Fansidar (pyrimethamine/sulfadoxine) on the dynamics of gametocytemia. Schoolchildren peripheral blood films positive for P. falciparum gametocytes were identified in a malaria-endemic area of Mozambique. The children were randomly allocated into two groups to receive chloroquine or pyrimethamine/sulfadoxine, and were followed for 28 days after treatment. In patients harboring drug-sensitive parasites, asexual parasitemias were cleared by day 4, but gametocytes persisted for an additional 17 days. The prevalence of the asexual parasites was 67.6% in the chloroquine-treated group at day 0 and 61.1% at day 28, whereas in the pyrimethamine/sulfadoxine treated group, the initial parasite prevalence of 70.7% was reduced to 2.4% at day 28, suggesting a high prevalence of chloroquine-resistant parasites. On day 0, gametocyte prevalence was 59.5% in the chloroquine-treated group and in 68.3% in the pyrimethamine/sulfadoxine-treated group; these values were reduced to 5.6% and 2.4%, respectively, at day 28. Our results suggest strongly that there is no induction of gametocytogenesis by either course of chemotherapy.

Adolescent↗

PubMed1995

Do transition grants help rural hospitals?

Congress introduced the Rural Health Care Transition (RHCT) Grant Program in 1989 to assist financially troubled, small rural hospitals. This article discusses grant effects on the second cohort of hospitals to complete their 3-year grants. Although three-quarters of the grantees implemented all or most of their goals, 11 percent could not implement a viable project. Grantees added or upgraded 523 services with the help of their grants, especially outpatient and social services, most of them financially self-supporting. Except among the largest hospitals, there was no evidence that the grants improved grantee finances. Management appeared unaffected by the grants.

Centers for Medicare and Medicaid Services, U.S.↗

PubMed1995

A comparative breastfeeding study in two contrasting areas.

An apparent decline in breastfeeding rates motivated health visiting staff within Hillingdon Community Health Trust to undertake a research project on infant feeding practice. Margaret Buckell and Rosemary Thompson describe a study to measure intent to breastfeed, breastfeeding initiation rates and feeding outcomes in two contrasting areas of Hillingdon, an outer London borough, and to identify areas for further work to improve breastfeeding levels.

Breast Feeding↗

PubMed1995

Participative decision making: multidisciplinary team involvement in unit design.

This article describes the multidisciplinary team's input into the design and construction of an Epilepsy Monitoring Unit. The unit construction was a collaborative effort of a multidisciplinary team based in part on patient input as well as economic and efficiency factors. The Unit has resulted in long term rewards for both patients and staff. Patients benefit from the friendly environment created and staff benefits are due to the increased efficiency of the unit--working smarter not harder and the knowledge that staff nurses were an integral part of the planning process of this highly successful project.

Decision Making, Organizational↗

PubMed1994

The influence of increased health care costs on general practitioner consultations and prescription collection.

AIM: Increased health service charges have led to concern that some patients may be unable to meet these costs, which could compromise their care. Increased costs may affect general practitioner attendance, and/or the collection of a prescription. This study examines both of these factors. METHODS: Between 18 August and 14 September 1992, questionnaires were sent to the consenting patients of 19 general practitioners from the Hutt Valley requesting information regarding the general practice (GP) visit and the prescription. The information included the reason for the GP visit, whether there was any delay and its duration, the reason for any delay, the cost of the visit and whether a prescription was received. Data regarding the prescription included the cost and whether all, some, or none of the items were uplifted, and whether the patient had a community service card. RESULTS: 489 (86%) returned completed questionnaires and 426 received a prescription. Of these, 164 were group 1 community service card holders; one was a group 2 community service card holder; 186 were group 3; 59 did not specify their group; 18 had a chronic-user card. Forty percent (194 patients), delayed going to their doctor, 118 by more than 3 days. The most common reasons for delay were hope that their condition may improve spontaneously and the cost of the consultation or prescription. Possession of a community service card was a significant factor in delay with group 3 (high wage earners) more likely to delay than group 1 (p < 0.0005). Only two patients did not present their prescription. Ninety-three percent of those receiving a prescription presented for dispensing within 24 hours. Ninety-two percent of patients paid for all their prescription items. CONCLUSIONS: Delay in obtaining treatment is common and occurs primarily at the general practitioner consultation. It primarily affects those individuals who were classified as group 3, the group that has taken the burden of recent health service charges increases.

Adolescent↗

PubMed1994

Sexual differentiation of brain and behavior in the zebra finch: critical periods for effects of early estrogen treatment.

In order to determine the critical period(s) during which estrogen alters sexually dimorphic behavior and neuroanatomy in zebra finches (Poephila guttata), nestlings were injected daily with 20 micrograms estradiol benzoate (EB) during posthatching week 1, week 2, week 3, or weeks 1, 2, and 3. At 7 months of age, birds were implanted with testosterone propionate and tested with female partners for singing, dancing, and copulatory mounting. Brains were subsequently processed for morphometry, and the volumes of the song system nuclei HVC, area X, and RA and the soma sizes and densities of neurons in RA were determined. Males given EB during week 1 failed to mount. Females given EB during week 1 were fully masculinized with respect to dancing and RA neuron soma size and density, and were partially masculinized with respect to song nuclei volumes and singing. Treatment beginning after week 1 was ineffective or less effective for all measures. Only for RA neuron measures was treatment for all three weeks more effective than week 1 treatment. Thus the first post-hatching week is the most influential period of those tested for effects of exogenous estrogen on sexual differentiation in this species, and is a period during which both masculinization of females and demasculinization of males is possible.

Animals↗

PubMed1994

The anti-infarct effect of an adenosine A1-selective agonist is diminished after prolonged infusion as is the cardioprotective effect of ischaemic preconditioning in rabbit heart.

Our aim was to determine whether adenosine A1 receptor-mediated protection could be maintained for a prolonged period of time by a continuous infusion of an A1-selective agonist. To produce myocardial infarction a branch of the left coronary artery of rabbit hearts was occluded for 30 min and reperfused for 3 h. Infarct size was determined with tetrazolium staining. Prior to the 30 min ischaemia, rabbits were subjected to one of the following six protocols: (1) 6 h i.v. saline infusion; (2) 6 h i.v. CCPA (0.043 mg/kg/h) infusion; (3) 72 h saline infusion; (4) 72 h CCPA infusion; (5) 72 h CCPA infusion plus preconditioning with 5 min ischaemia followed by 10 min reperfusion; (6) 72 h saline infusion plus preconditioning. The 6 h CCPA infusion group had significantly smaller infarct sizes than the 6 h vehicle group. 16.2 +/- 2.9% infarction of the ischaemic region v 39.5 +/- 2.6%, P < 0.01. Infarction in the 72 h CCPA infusion group (37.7 +/- 2.7%) was the same as in the 72 h vehicle group (35.2 +/- 3.1%). Ischaemic preconditioning could not limit infarct size in 72 h CCPA animals (%infarction; 29.1 +/- 4.6%) but did protect animals given vehicle for 72 h (8.4 +/- 1.2%, P < 0.01). After 72 h infusion of CCPA, both the cardioprotective effect of adenosine A1-selective agonist and ischaemic preconditioning were attenuated. These findings indicate that: (1) the myocytes become desensitized to the protective effect of CCPA with prolonged exposure; and (2) ischaemic preconditioning is no longer protective when tachyphylaxis to CCPA occurs.

Acetylcholine↗

PubMed1994

Computer assisted recognition and quantitation of the effects of airborne chemicals acting at different areas of the respiratory tract in mice.

The pattern and timing of a normal breath in unanesthetized mice was analyzed from measurement of inspiratory and expiratory airflows (VI and VE). Airflow was measured via a differential pressure transducer, attached to a pneumotachograph, which itself was attached to a body plethysmograph into which a mouse was placed. The analog voltage from the differential pressure transducer was digitized and stored for analysis on a microcomputer. Criteria were developed to classify each breath as normal (N) or belonging into one of seven abnormal categories. The abnormal categories were arrived at by computer analysis, recognizing specific modifications of the normal pattern into patterns of: sensory irritation of the upper respiratory tract (S), airflow limitation within the conducting airways of the lungs (A) or pulmonary irritation at the alveolar level (P). Combinations of these effects, i.e., S+A, P+A, P+S and P+S+A were also recognized. Computer analysis of each breath also permitted quantitative evaluation of the degree of S, A or P abnormalities. To induce each type of effect we used inhalation exposures to 2-chlorobenzylchloride, carbamylcholine or propranolol. We propose that this approach will permit rapid evaluation of the possible effects of airborne chemicals at three levels of the respiratory tract, with the classification of the type of effect easily obtained in an objective way using well defined criteria, followed by quantitation of the degree of each effect.

Administration, Inhalation↗

PubMed1994

The influence of Maloprim chemoprophylaxis on cellular and humoral immune responses to Plasmodium falciparum asexual blood stage antigens in schoolchildren living in a malaria endemic area of Mozambique.

We examined the impact of chemoprophylaxis on the cellular and humoral immune responses to polypeptides of the asexual Plasmodium falciparum blood stage antigens, the glutamate rich protein GLURP and Pf155/RESA, both of which in previous field studies have been identified as potentially protective antigens. The study was carried out in the Escola Primária de Lingamo, a primary school in a suburban area of Maputo, Mozambique. A cohort of 392 schoolchildren (aged 7-12 years) was randomly allocated to two equal groups, one receiving chemoprophylaxis with dapsone/pyrimethamine (Maloprim), the other receiving placebo every week from December 1989 to November 1990. The groups were then followed until November 1991 without chemoprophylaxis. Cellular responses to immunodominant epitopes from Pf155/RESA and GLURP, and to non malaria antigens C. albicans and PPD, were assessed by lymphocyte proliferation assays in vitro. Anti-GLURP and anti-Pf155/RESA antibodies were detected by enzyme-linked immunosorbent assay (ELISA) and erythrocyte membrane immunofluorescence (EMIF), and total anti-P. falciparum antibodies were measured by indirect fluorescent antibody test (IFAT). Immunological reactivities were evaluated every six months, at the end of the rainy season and at the end of the dry season, both during the period of chemoprophylaxis and during the follow-up. The antibody response rate to the GLURP was lower in the Maloprim group than in the placebo group during the intervention phase. The lymphoproliferative response rate to the malaria antigens was significantly lower at the end of the rainy season than at the end of the dry season, but the difference between the experimental group and the control group of schoolchildren was not statistically significant. These results suggest that the antibody responses to the GLURP molecule and partly to the Pf155/RESA antigen in this study population were shortlived and dependent on frequent boostering, but whether these antigens play a role in the development of natural clinical immunity remains open. In the experimental group of schoolchildren weekly chemoprophylaxis successfully reduced the parasite rate during the rainy season from 43% to 4%, and during the dry season from 18% to 0%. Chemoprophylaxis may therefore have a useful role in combination with another partially effective malaria control measure such as insecticide-impregnated bed nets or a malaria vaccine.

Animals↗