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Biomedical subjects

R Williams

Publications and source records attributed to R Williams.

At least 379 records · Page 21Linked to original sources
PubMed1997

The association of nocturnal asthma with asthma severity.

The objective of this study is to assess nocturnal asthma as a marker for poor control of asthma. Cross-sectional study of asthmatic patients was conducted in six general practices in East Anglia, England. Subjects were 240 asthma patients, between the ages of 20 and 54 years, from the above general practices. A continuous asthma severity score (range 6-26), consisting of the summation of ordinal responses to questions regarding asthma symptoms during the last 6 months, was used for analysis. The crude association between nocturnal asthma and severity score was statistically highly significant. Regression analysis suggests that, after controlling for possible confounding variables, there remains a strong association between nocturnal asthma (NA) and severity, which is modified by self-report of current consultation for "nervous/emotional trouble" (current NT). In the absence of current NT, NA raises the severity score by 5.3 (95% CI 4.5, 6.2), whereas in the presence of current NT, NA raises the severity score by 8.2 (95% CI 4.8, 11.6). NA appears promising as a marker for poorly controlled asthma. Confirmation of the association found in this study by objective measures of severity would strengthen the utility of NA as a marker.

Adult↗
PubMed1997

Clinical and laboratory evaluation of powered electric toothbrushes: comparative efficacy of two powered brushing instruments in furcations and interproximal areas.

The purpose of this study was to compare the efficacy of two powered brushing instruments (Rota-dent, Pro-Dentec Inc. and Interplak, Bausch and Lomb Inc.) for control of plaque and gingivitis in interproximal spaces and furcations. Thirty-five patients, randomly selected from a pool of post-active therapy, periodontal surgical cases, completed this study. A split-mouth design was utilized in this twelve-week trial with each patient acting as his/her own control. Subjects alternately brushed one-half of their mouths with each of the instruments: a crossover in the brushing pattern occurred at six weeks. Single-blind clinical assessments were made by a calibrated investigator at baseline, six and twelve weeks. Gingival Index (GI), Plaque Index (PI) and Papillary Bleeding Index (PBI) were determined in interproximal and furcation areas. Mean percent reductions from baseline for GI, PI and PBI at the end of twelve weeks were 72%, 61% and 70%, respectively for the Rota-dent, and 46%, 43% and 27%, respectively for the Interplak. One-way analyses of variance (ANOVA) and co-variance (ANCOVA) indicate that the Rota-dent was significantly more effective (p < 0.001) than the Interplak in controlling plaque and gingivitis in furcation and interproximal areas with clinically relevant differences in all indices measured.

Adult↗
PubMed1997

Nutrition assessment in children with sickle cell disease.

Children with sickle cell disease have decreased height and weight when compared with their peers. Although exact reasons for poor growth have not been established, increased calorie and protein needs and deficiencies in zinc, folic acid, and vitamins A, C, and E may be factors. To determine whether inadequate nutrient intake contributes to this poor growth, we conducted a survey of the nutrition knowledge and practices of families affected by sickle cell disease. Sixty-one patients with a median age of 8 years (range, 13 months to 17 years) participated in the study. Patients with homozygous S hemoglobin (sickle cell) disease (Hb SS, n = 34) and sickle beta zero thalassemia (Hb S beta zero-thalassemia, n = 2) were combined; 19% were below the fifth percentile for height. The other patients, with sickle hemoglobin C disease (Hb SC, n = 21) and sickle beta plus thalassemia (Hb beta(+)-thalassemia, n = 4), were grouped, and 4% were below the fifth percentile for height (P = .043). Ninety percent of the study patients or their parents were familiar with the food groups indicated on the US Department of Agriculture's Food Guide Pyramid, but most patients failed to consume appropriate amounts from those groups. Although two thirds of the patients ate the recommended number of servings daily from the meat group, only 20% to 31% of the recommended servings from each of the other food groups was consumed. This was possibly related to low socioeconomic status. The patients in the Hb SS group ate significantly less from the bread (P < .037) and milk (P < .022) categories than the patients in the Hb SC group. Fifty-nine percent of families had incomes below the poverty level, and 79% participated in a food assistance program. We conclude that the nutrient intake of patients with sickle cell disease is often inadequate. Education for patients with sickle cell disease should focus on (1) specific nutrient needs, with proper distribution of dietary intake among the food groups, (2) ways to provide nutritious meals on a limited income, and (3) methods for increasing calorie and protein intake.

Adolescent↗
PubMed1997

Experimental infection of vaccinated slaughter ostriches with virulent Newcastle disease virus.

A virulent Newcastle disease virus (NDV) isolate from an outbreak in commercial poultry, with virulence indices of MDT = 47-48 h; IVPI = 2,17 and ICPI = 1,8; was used to inoculate 10x vaccinated (standard poultry vaccines) as well as 10x unvaccinated slaughter ostriches via intratracheal, ocular and nasal routes, in a controlled environment. All unvaccinated ostriches developed clinical signs (mainly respiratory); two of them died while the other eight recovered. No vaccinated ostriches developed any clinical signs. All remaining (18) ostriches were slaughtered 14 d after the last mortality. Virulent NDV could be re-isolated from the dead birds, but not from organs, muscle (fresh), muscle (24 h chilled), gastro-intestinal tract, bone-marrow or respiratory system taken from the slaughtered ostriches. It is suggested that it would be extremely unlikely that the international trade in ostrich meat could act as a mechanism for spreading virulent NDV from endemic to non-endemic parts of the world.

Animals↗
PubMed1997

Parent-child interaction therapy and dysfluency: a single-case study.

The hypothesis that the modification of parent-child interaction would reduce the dysfluency of a pre-school child was tested in an experimental single-case study. The subject, a four-year-old boy with a moderate to severe stutter, and his parents attended their local clinic for a total of 17 weeks. On each visit, 20-minute play periods with each parent were recorded and measures of fluency taken. No advice was offered in the first six weeks and these measures were used as a baseline for subsequent therapy. Therapy was given over the next six weeks. The parents were advised to make changes in their style of interaction and were asked to practise these at home each day. During the final five weeks, which served as consolidation, the parents continued to practise their skills at home but no new advice was offered. The analysis found no significant trend in the child's dysfluency during the baseline period, a significant improvement during therapy and stabilisation of the lower rate of dysfluencies during the maintenance period.

Child, Preschool↗
PubMed1997

Comparison of ELISA and HI for detection of antibodies against Wesselsbron disease virus.

A two-graph Receiver Operating Characteristic analysis was done to determine the optimal cut-off value of an indirect enzyme-linked immunosorbent assay (ELISA) for detection of antibodies to Wesselsbron disease (WSL) virus. When ELISA and haemagglutination-inhibition (HI) results of WSL-positive and WSL-negative control sheep sera were compared, the sensitivity of ELISA was 97.9% and that of HI, 87.5%, while the specificity of ELISA and HI were 95.7% and 100%, respectively. The ELISA's superior sensitivity was confirmed by the results of the two assays performed on a simulated range of low-positive sera, which showed that the ELISA was able to detect WSL-antibody levels at least ten times lower than those the HI could. The ELISA was also less cross-reactive than the HI to guinea-pig antisera against nine flaviviruses relevant to southern Africa. The combination of the ELISA's ability to test untreated sera in single dilution and its superior sensitivity and lower cross-reactivity as compared to that of the traditional HI, makes it the assay of choice for automation and large-scale screening of animals for antibodies to WSL virus.

Animals↗
PubMed1996

Transplantation for fulminant hepatic failure: comparing tacrolimus versus cyclosporine for immunosuppression and the outcome in elective transplants. European FK506 Liver Study Group.

Within the multicenter European FK506 (tacrolimus) liver study, patients who received transplants for fulminant hepatic failure (FHF) were stratified separately from those having an elective transplant procedure. At 2-year follow-up, in addition to a comparison of the outcome between these two clinical groups, we report the efficacy and safety of tacrolimus primary immunosuppression (n=32) as compared with a cyclosporine-based regimen (n=23) in FHF. The FHF patients experienced more episodes of acute rejection and sepsis with reduced patient and graft survival rates compared with the elective group (e.g., retransplantation rate of 10/44 [22.7%] vs. 47/485 [9.7%], respectively). Among the FHF patients, tacrolimus reduced the actuarial incidence of acute rejection compared with patients treated with cyclosporine, and whereas refractory acute and chronic rejection occurred in four (17.4%) and two patients (8.7%), respectively, treated with cyclosporine, no rejection episodes were recorded in patients receiving tacrolimus. No difference in the actuarial patient or graft survival rates was observed between the two groups. Patients treated with tacrolimus tended to have a lower incidence of infection (pneumonia, 19.0% vs. 26.1%; cytomegalovirus infection, 9.5% vs. 26.1%; and sepsis, 23.8% vs. 39.1%). Corticosteroid dosage requirements were reduced in the tacrolimus-treated group with the cumulative dosage exposure from 20.8% to 37.2% lower on a monthly basis. No significant differences in adverse events attributable to the immunosuppressive drugs were found.

Cyclosporine↗
PubMed1996

Cellular expression of the immediate early transcription factors Nurr1 and NGFI-B suggests a gene regulatory role in several brain regions including the nigrostriatal dopamine system.

Nurr1 and NGFI-B are closely related orphan members of the steroid-thyroid hormone receptor family involved in immediate early responses to stimuli such as growth factors. In-situ hybridization in the developing and adult mouse and rat demonstrated Nurr1 mRNA in several regions during early central nervous system (CNS) development. Expression persisted through the pre- and postnatal periods and was also found in several areas in the adult CNS. Positive areas include the olfactory bulb, parts of the cortex, the hippocampal formation and substantia nigra where Nurr1 and tyrosine hydroxylase mRNAs were co-expressed. 6-Hydroxydopamine-induced degeneration of mesencephalic dopamine neurons led to a corresponding loss of Nurr1 mRNA, demonstrating a link between Nurr1 and dopaminergic neurons. NGFI-B mRNA was not found in the prenatal CNS but was highly expressed in the adult brain in many areas including the olfactory bulb, cortex, basal ganglia and hippocampus. The spatiotemporal distribution of Nurr1 and NGFI-B mRNAs suggests that these transcription factors are involved in the development and maturation of specific sets of CNS neurons. The experimental data imply that one of these functions may be to control gene regulatory events important for development and function of those neurons that degenerate in patients with Parkinson's disease.

Animals↗
PubMed1996

Rapamycin resistance in ataxia-telangiectasia.

The gene mutated in the human genetic disorder ataxia-telangiectasia (A-T) has been described recently (Savitsky et al., 1995a) and the complete coding sequence of this gene, ATM, has been reported (Savitsky et al., 1995b). The derived amino acid sequence demonstrates significant homologies to several proteins containing a phosphatidylinositol 3-kinase (PI3-kinase) domain, including the yeast TOR proteins and the human protein FRAP. Since the TOR and FRAP proteins are targets for the immunosuppressive drug rapamycin, we have investigated the effects of this compound on A-T cells. We report here that 3 A-T cell lines are more resistant than control cells to rapamycin's growth inhibiting effects but were more sensitive to the PI3-kinase inhibitor wortmannin. As expected rapamycin (1 nM) inhibited the rate of exit of control cells from G1 phase but failed to perturb the progression of A-T cells. This difference in cell cycle progress after rapamycin treatment is reflected in ribosomal S6 protein kinase (p70S6k) by both a downward mobility shift on SDS-PAGE and inhibition of activity. Furthermore, the G1 phase cyclin-dependent kinase, cyclin E-cdk2, was rapidly inhibited in control cells post-treatment, whereas in A-T cells it took considerably longer to observe inhibition. There was no evidence that a GST-FKBP12 fusion protein specifically precipitated the ATM protein in the presence of rapamycin in either cell type. These results demonstrate that the ATM protein is not a direct target for rapamycin but its functional loss renders cells more resistant to this compound.

Amino Acid Sequence↗
PubMed1996

Defect in multiple cell cycle checkpoints in ataxia-telangiectasia postirradiation.

The recent description of a novel gene (ATM) mutated in ataxia-telangiectasia (A-T), with homologies to genes encoding proteins involved in both G1/S and G2/M checkpoint control, points to a common defect in cell cycle control in A-T operating through the cyclin-dependent kinases. In this report we demonstrate that cyclin-dependent kinases are resistant to inhibition by ionizing radiation exposure in A-T cells, and this appears to be due to insufficient induction of WAF1. Exposure of control lymphoblastoid cells to radiation during S phase and in G2 phase causes a rapid inhibition of cyclin A-Cdk2 and cyclin B-Cdc2 activities, respectively. Irradiation led to a 5-20-fold increase in Cdk-associated WAF1 in these cells, which accounts at least in part for the decrease in cyclin-dependent kinase activity. In contrast, radiation did not inhibit any of the cyclin-dependent kinase activities in S phase or G2 phase in A-T cells at short times after irradiation nor was there any significant change in the level of Cdk-associated WAF1 compared to unirradiated cells. These results are similar to those reported previously for the G1 checkpoint and provide additional evidence for the involvement of ATM at multiple points in cell cycle regulation.

Ataxia Telangiectasia↗
PubMed1996

NHLBI Family Heart Study: objectives and design.

The NHLBI Family Heart Study is a multicenter, population-based study of genetic and nongenetic determinants of coronary heart disease (CHD), atherosclerosis, and cardiovascular risk factors. In phase I, 2,000 randomly selected participants and 2,000 with family histories of CHD were identified among 14,592 middle-aged participants in epidemiologic studies. Medical histories from these individuals, their parents, and their siblings were used to calculate family risk scores that compared the number of reported and validated CHD events with the number expected based on the size, sex, and age of family members. A total of 657 families with the highest risk scores and early-onset CHD and 588 randomly sampled families had clinic examinations that included electrocardiograms, carotid artery ultrasound scans, spirometry, measurements of body size, blood pressure, lipids, lipoproteins, hemostatic factors, insulin, glucose, and routine chemistries. Additional biochemical and genetic studies are being performed on selected participants. Serum, plasma, lymphocytes, red cells, and DNA are stored for future studies, including genotyping of candidate genes and anonymous markers. Contributions of genes, shared and individual environments, and behaviors to variations in risk factors, preclinical atherosclerosis, and CHD will be estimated. Linkage studies, including the quantitative trait loci approach, are planned.

Age of Onset↗