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Biomedical subjects

S Walters

Publications and source records attributed to S Walters.

At least 55 records · Page 3Linked to original sources
PubMed1999

The interaction of TSH receptor autoantibodies with 125I-labelled TSH receptor.

Detergent-solubilized porcine TSH receptor (TSHR) has been labeled with 125I using a monoclonal antibody to the C-terminal domain of the receptor. The ability of sera containing TSHR autoantibody to immunoprecipitate the labeled receptor was then investigated. Sera negative for TSHR autoantibody (as judged by assays based on inhibition of labeled TSH binding to detergent-solubilized porcine TSHR) immunoprecipitated about 4% of the labeled receptor, whereas sera with high levels of receptor autoantibody immunoprecipitated more than 25% of the labeled receptor. The ability to immunoprecipitate labeled TSHR correlated well with ability of the sera to inhibit labeled TSH binding to the receptor (r = 0.92; n = 63), and this is consistent with TSHR autoantibodies in these samples being directed principally to a region of the receptor closely related to the TSH binding site. Preincubation of labeled TSHR with unlabeled TSH before reaction with test sera inhibited the immunoprecipitation reaction, providing further evidence for a close relationship between the TSHR autoantibody binding site(s) and the TSH binding site. This was the case whether the sera had TSH agonist (i.e., thyroid stimulating) or TSH antagonist (i.e., blocking) activities, thus, providing no clear evidence for different regions of the TSHR being involved in forming the binding site(s) for TSHR autoantibodies with stimulating and with blocking activities. The ability of TSHR autoantibodies to stimulate cyclic AMP production in isolated porcine thyroid cells was compared with their ability to immunoprecipitate labeled porcine TSHR. A significant correlation was observed (r = 0.58; n = 50; P < 0.001) and the correlation was improved when stimulation of cyclic AMP production was compared with inhibition of labeled TSH binding to porcine TSHR (r = 0.76). Overall, our results indicate that TSHR autoantibodies bind principally to a region on the TSHR closely related to the TSH binding site, and this seems to be the case whether the autoantibodies act as TSH agonists or antagonists.

Animals↗
PubMed1999

Leptin binding activity changes with age: the link between leptin and puberty.

The timing of the physical transition from child to adult is determined by a biological clock that switches off the pituitary gonadal axis during infancy until puberty. Body composition (and in particular, fat mass), through leptin, are critical signals to this clock. However, no direct relationship between leptin and puberty has been demonstrated. Leptin is bound in the circulation by a high-affinity binding protein, which has been identified as a soluble leptin receptor. We found circulating levels of leptin binding activity (LBA) to be low at birth, to be high in the prepubertal years, to fall through puberty, and then to remain stable during adult life. LBA correlated with pubertal status in both boys and girls. We postulate that the fall in LBA, associated with increasing age and puberty, reflects a reduction in expression of truncated leptin receptors, and leptin is then available to the full-length receptor, which transmits the biological signal for leptin. The high levels of LBA occur during the years when the pituitary gonadal axis is quiescent. Thus, the change in LBA could explain how leptin regulates puberty.

Adolescent↗
PubMed1999

Paediatric treatment issues.

Compared with the therapeutic options available for the treatment of HIV infection in adults, the therapeutic options available for the treatment of paediatric patients is limited. New anti-HIV agents are needed to broaden the range of effective therapeutic options. However, several factors need to be considered when treating HIV infection in paediatric patients. It is important that the antiviral combination is potent and has at least one agent with adequate CNS penetration. In addition, to aid adherence it is important that any new agent is administered once daily and that the paediatric formulation is palatable. Furthermore, a good safety profile and compatibility with other anti-HIV drugs is also important. Efavirenz has many properties that make it suitable for the treatment of HIV infection especially in paediatric patients. In addition, recent clinical evidence indicate that efavirenz will be a very useful drug for paediatric therapy.

Administration, Oral↗
PubMed1998

Review of uptake of interventions to reduce mother to child transmission of HIV by women aware of their HIV status.

OBJECTIVES: To examine the change in uptake of interventions to reduce transmission of HIV from mothers to infants from January 1994 to July 1997. DESIGN: Review of mother-infant pairs who presented for infant diagnosis of HIV infection. SETTING: Central London hospital with facilities for diagnosis of infant HIV infection. SUBJECTS: 57 consecutive mother-infant pairs, mainly from central London but also referred from surrounding hospitals. INTERVENTIONS: Data were collected on mother's country of origin; CD4 count at delivery; plasma HIV RNA copies/ml; mode of delivery; antiretroviral therapy; infant feeding; and HIV infection in infants. MAIN OUTCOME MEASURES: HIV infection of infants. RESULTS: The vertical transmission rate was 12% (7 pairs; 95% confidence interval 3% to 22%). All mothers chose not to breast feed. The caesarean section rate was 53% (30/57). Antiretroviral therapy was taken by 68.5% (39/57) of mother-infant pairs. With antiretroviral therapy or caesarean section, or both, transmission occurred in 6% (0% to 13%) of pairs (3/50). During the 24 months of 1994 and 1995, 21% (4/19) of infants were infected with HIV; 7.9% (3/38) were infected over the 19 months January 1996 to July 1997. The caesarean section rate did not change over these periods. Use of antiretroviral therapy increased from 31.5% (6/19) to 86.8% (33/38) (P < 0.0001). CONCLUSION: Women with a diagnosis of HIV infection acted to reduce the risk of transmission to their infants. Uptake of antiretroviral therapy increased significantly over time, and the caesarean section rate was persistently high.

Africa↗
PubMed1998

Chickenpox in childhood. A review prepared for the UK Advisory Group on Chickenpox on behalf of the British Society for the Study of Infection.

Chickenpox in childhood is a milder condition than in older patients, but serious and even fatal complications may occur. These occur especially in immunosuppressed individuals, but can also be seen in normal children. The commonest of these is secondary bacterial infection with staphylococci or streptococci. Reye's syndrome is now rare in chickenpox, since aspirin no longer used in treatment. Aciclovir and VZIG (varicella zoster immune globulin) have a role in the management of chickenpox in the immunosuppressed or immunodeficient child, and aciclovir may be valuable in managing some normal children. Chickenpox should not always be considered a trivial illness.

Acyclovir↗
PubMed1998

Variations in hospitalization rates for asthma among black and minority ethnic communities.

In response to the introduction of ethnic monitoring within the U.K. hospital inpatient data set, this study investigates the variations in secondary healthcare utilization by Black and minority ethnic communities whose cause of admission is related to asthma. The study examines all residents of the West Midlands: over 5 million people, of whom 8.5% are from Black and minority ethnic groups. A retrospective study of 15,921 asthma-related hospital admissions, from 1 April 1995 to 31 March 1996, was carried out. Age-standardized admission rates were higher in all Black and minority ethnic groups studied than in the White group. There were elevated rates in Black children aged 5-14 years, and particular differences were observed for Indian and Bangladeshi men and women aged 65 years or over. Emergency admissions to hospital for asthma were strongly associated with patients' socioeconomic background but this was largely observed for Black and minority ethnic groups that also generally experience high levels of deprivation. The findings support previous studies which suggest that hospital utilization rates for asthma among people from Black and minority ethnic groups are high compared with the White group, despite little evidence in measured prevalence. This study suggests that ethnic background is more important in asthma admissions than deprivation, which raises serious concerns on the appropriateness and quality of asthma care for these patient groups within our society. Future studies need to examine pathways to care, that is the health-seeking behaviour of Black and minority ethnic groups, the type of treatment received at the primary care level and referral patterns to secondary care.

Adolescent↗
PubMed1998

The SF36 as an outcome measure of services for end stage renal failure.

OBJECTIVE: To evaluate the use of the short form 36 (SF36) as a measure of health related quality of life of patients with end stage renal failure, document the results, and investigate factors, including mode of treatment, which may influence it. DESIGN: Cross sectional survey of patients with end stage renal failure, with the standard United Kingdom version of the SF36 supplemented by specific questions for end stage renal failure. SETTING: A teaching hospital renal unit. SUBJECTS AND METHODS: 660 patients treated at the Sheffield Kidney Institute by haemodialysis, peritoneal dialysis, and transplantation. Internal consistency, percentage of maximal or minimal responses, SF36 scores, effect sizes, correlations between independent predictor variables and individual dimension scores of the SF36. Multiple regression analysis of the SF36 scores for the physical functioning, vitality, and mental health dimensions against treatment, age, risk (comorbidity) score, and other independent variables. RESULTS: A high response rate was achieved. Internal consistency was good. There were no floor or ceiling effects other than for the two "role" dimensions. Overall health related quality of life was poor compared with the general population. Having a functioning transplant was a significant predictor of higher score in the three dimensions (physical functioning, vitality, and mental health) for which multiple regression models were constructed. Age, sex, comorbidity, duration of treatment, level of social and emotional support, household numbers, and hospital dialysis were also (variably) significant predictors. CONCLUSIONS: The SF36 is a practical and consistent questionnaire in this context, and there is evidence to support its construct validity. Overall the health related quality of life of these patients is poor, although transplantation is associated with higher scores independently of the effect of age and comorbidity. Age, comorbidity, and sex are also predictive of the scores attained in the three dimensions studied. Further studies are required to ascertain whether altering those predictor variables which are under the influence of professional carers is associated with changes in health related quality of life, and thus confirm the value of this outcome as a measure of quality of care.

Data Collection↗
PubMed1997

T-cell immunity to peptide epitopes of liver-stage antigen 1 in an area of Papua New Guinea in which malaria is holoendemic.

Liver-stage antigen 1 (LSA1) is one of several pre-erythrocytic antigens considered for inclusion in a multiantigen, multistage subunit vaccine against falciparum malaria. We examined T-cell proliferation and cytokine responses to peptides corresponding to amino acids 84 to 107, 1813 to 1835, and 1888 to 1909 of LSA1 in asymptomatic adults living in an area of Papua New Guinea where malaria is holoendemic. Whereas T cells from North Americans never exposed to malaria did not respond to any of the peptides, those from 52 of 55 adults from the area where malaria is endemic had vigorous proliferation responses to one or more of the LSA1 peptides (mean stimulation indices of 6.8 to 7.2). Gamma interferon (IFN-gamma) production driven by LSA1 peptides ranged from 34 to more than 3,500 pg/2 x 10(6) cells, was derived primarily from CD8+ cells, and was dissociated from T-cell proliferation. The frequencies of IFN-gamma response to the amino acid 1819 to 1835 and 1888 to 1909 peptides were significantly greater than that to the amino acid 84 to 107 peptide (87 and 88% versus 33% of subjects; P < 0.0001). In contrast to proliferation and IFN-gamma, interleukin 4 (IL-4) and/or IL-5 responses to LSA1 peptides were detected in only 18% of the subjects. These data show that T-cell immunity to epitopes in the N- and C-terminal regions of LSA1 are common in persons living in this area of Papua New Guinea where malaria is endemic. The dominance of type 1 CD8 cell IFN-gamma responses is consistent with a role for this T-cell population in immunity to liver-stage Plasmodium falciparum in humans.

Adult↗
PubMed1997

Short term variations in hospital admissions and mortality and particulate air pollution.

OBJECTIVES: To determine the presence and magnitude of any relation between short term variations in ambient concentrations of particulate matter under 10 microns in diameter (PM10) and hospital admissions and mortality in Birmingham, United Kingdom. To find the relative risk associated with various concentrations of PM10, and to estimate the potential public health benefit of reducing PM10 to below various thresholds. METHODS: Retrospective ecological study. Air pollution data were taken from a national network monitoring station between 1 April 1992 and 31 March 1994, and weather data for the same period from the University of Birmingham Weather Service. Daily total hospital admissions for the same period for asthma, bronchitis, pneumonia, chronic obstructive pulmonary disease (COPD), acute ischaemic heart disease, acute cerebrovascular disease, all respiratory conditions, and all circulatory conditions were obtained from the West Midlands Regional Health Authority, as well as daily total deaths from 1 April 1992 to 31 December 1994 for chronic obstructive pulmonary disease, pneumonia, all respiratory diseases, all circulatory diseases, and all causes. Multiple linear regression models were constructed after adjusting for confounding factors (day of week, month, linear trend, relative humidity, and temperature). Relative risk of admission at various thresholds of PM10 was calculated with the model, by comparing risk of admission over the threshold with mean risk of admission over the whole period. Potential public health benefits at various thresholds were calculated with the model to predict the number of admissions of deaths that could be saved if, on each day that the PM10 had exceeded that threshold, it had instead been kept at the threshold level. RESULTS: Significant associations were found between all respiratory admissions, cerebrovascular admissions, and bronchitis admissions and PM10 on the same day. Pneumonia, all respiratory admissions, and asthma admissions were significantly associated with the mean PM10 values for the past three days. Deaths from COPD, all circulatory deaths, and all causes mortality were significantly associated with PM10 24 hours previously, and COPD deaths also with PM10 on the same day. The effect of a 10 micrograms/m3 rise in PM10 was estimated to represent a 2.4% increase in respiratory admissions, a 2.1% increase in cerebrovascular admissions, and a 1.1% increase in all causes mortality. In a population of 1 million, this would represent 0.5 extra respiratory admissions and 0.3 extra deaths. The increase in relative risk was linear without evidence of a threshold. The impact of reducing PM10 to below 70 micrograms/m3 would be small, representing less than 0.1% of respiratory admissions and 0.2% all causes mortality. The impact would be greater at lower thresholds. CONCLUSION: Ambient outdoor concentrations of PM10 in the United Kingdom are significantly associated with several indicators of acute health effect. These associations are similar to and consistent with other studies. However, the estimated size of the public health effect is small, accounting for only a small proportion of hospital admissions and mortality over a two year period.

Air Pollutants↗
PubMed1997

An evaluation of a nurse-led ear care service in primary care: benefits and costs.

BACKGROUND: Nurses trained in ear care provide a new model for the provision of services in general practice, with the aim of cost-effective treatment of minor ear and hearing problems that affect well-being and quality of life. AIM: To compare a prospective observational cohort study measuring health outcomes and resource use for patients with ear or hearing problems treated by nurses trained in ear care with similar patients treated by standard practice. METHOD: A total of 438 Rotherham and 196 Barnsley patients aged 16 years or over received two self-completion questionnaires: questionnaire 1 (Q1) on the day of consultation and questionnaire 2 (Q2) after three weeks. Primary measured outcomes were changes in discomfort and pain; secondary outcomes included the effect on normal life, health status, patient satisfaction, and resources used. RESULTS: After adjusting for differences at Q1, by Q2 there was no statistical evidence of a difference in discomfort and pain reduction, or differential change in health status between areas. Satisfaction with treatment was significantly higher (P = 0.0001) in Rotherham (91%) than in Barnsley (82%). Average total general practitioner (GP) consultations were lower in Rotherham at 0.4 per patient with an average cost of 6.28 Pounds compared with Barnsley at 1.4 per patient and an average cost of 22.53 Pounds (P = 0.04). Barnsley GPs prescribed more drugs per case (6% of total costs compared with 1.5%) and used more systemic antibiotics (P = 0.001). CONCLUSIONS: Nurses trained in ear care reduce costs, GP workload, and the use of systemic antibiotics, while increasing patient satisfaction with care. With understanding and support from GPs, such nurses are an example of how expanded nursing roles bring benefits to general practice. Nurses trained in ear care reduce treatment costs, reduce the use of antibiotics, educate patients in ear care, increase patient satisfaction, and raise ear awareness.

Adult↗
PubMed1996

Systemic complications associated with bacterial tracheitis.

The toxic shock syndrome, septic shock, pulmonary oedema, and the acute respiratory distress syndrome (ARDS) were recognised in four children with bacterial tracheitis. ARDS has not previously been reported in association with bacterial tracheitis. Prompt recognition of the severe systemic complications of bacterial tracheitis could lead to a decrease in the morbidity and mortality of this condition.

Bacterial Infections↗
PubMed1995

Hospital admission rates for asthma and respiratory disease in the West Midlands: their relationship to air pollution levels.

BACKGROUND: A study was undertaken to determine the relationship between hospital admissions for asthma and all respiratory conditions in electoral wards in the West Midlands and ambient levels of smoke, sulphur dioxide, and nitrogen dioxide, and to establish whether the relationship is independent of social deprivation and ethnicity, and is different for young children and older individuals. METHODS: Data on hospital admissions for acute respiratory conditions were obtained by electoral ward from the West Midlands Regional Health Authority Information Department Körner inpatient data including asthma (ICD 493) and all acute respiratory disease (466, 480-486, 490-496) for the period April 1988 to March 1990. The population for each electoral ward, percentage of ward population that was from non-white ethnic groups, and Townsend deprivation score were all calculated from 1991 census information. Data on smoke and sulphur dioxide (SO2) levels were obtained for 24 wards in Birmingham, Coventry, Wolverhampton, Dudley, Stafford, and Burton-on-Trent, and on nitrogen dioxide (NO2) levels from 39 wards in the same local authority areas. All were background urban sites and most participated in the Warren Spring national quality control programme for SO2 and smoke monitoring. Indirect age-sex standardised hospitalisation rates (SHR) for all respiratory conditions and asthma were calculated using the 1991 rates for the West Midlands RHA as the standard. Multivariate regression models were used to assess the relationship between individual pollutants and the SHR. The Townsend score and percentage of the population from non-white ethnic groups were included in all models to adjust for ethnicity and socioeconomic deprivation. RESULTS: The SHR for asthma varied almost fourfold across the region, and all respiratory SHR showed more than three fold variation. Bivariate regression revealed both Townsend score and percentage of non-white individuals to be associated with SHR for asthma and all respiratory conditions at all ages, but not for children under 5 years. NO2 was associated with hospital admission rates for all ages including children under 5. SO2 and smoke were not associated with hospital admissions. Multivariate analysis including Townsend score and percentage of non-white subjects in the model revealed that NO2 was associated with hospital admission rates for all respiratory conditions only for children under 5. The Townsend score was associated with SHR for all respiratory conditions, and both the Townsend score and percentage of non-white subjects were associated with SHR for asthma in children under 5 in two of three models. The association between SHR for asthma and percentage of non-white subjects was negative. CONCLUSIONS: Socioeconomic deprivation, as measured by the Townsend score, is a significant predictor of hospital admission rates for respiratory disease in older individuals, and both the percentage of non-white subjects and the Townsend score are significant predictors of hospital admission rates for asthma in children. After correction for socioeconomic deprivation and ethnicity, background urban NO2 levels in the ward of residence are significantly associated with standardised hospital admission rates for all respiratory disease in children under 5. This may represent a causal effect of NO2 on the respiratory health of children, or the effect of confounding factors not corrected by use of the Townsend score.

Acute Disease↗