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Biomedical subjects

S Harding

Publications and source records attributed to S Harding.

At least 37 records · Page 2Linked to original sources
PubMed2000

Comparison of once- and twice-daily dosing of fluticasone propionate 200 micrograms per day administered by diskus device in patients with asthma treated with or without inhaled corticosteroids.

BACKGROUND: There are limited published data regarding the efficacy of once- versus twice-daily administration of flutica-sone propionate. OBJECTIVE: Our purpose was to evaluate the effectiveness of fluticasone propionate powder 200 microg/d administered as a once- or twice-daily dosage regimen in patients who were currently being treated with bronchodilators only (BD patients) and in patients who required inhaled corticosteroids for maintenance treatment of asthma (ICS patients). METHODS: Five hundred seventy patients were randomly assigned to receive one of the following inhaled treatments through the Diskus device (Glaxo Wellcome, Research Triangle Park, NC) for 12 weeks: fluticasone propionate 100 microg twice daily (FP100BID) or 200 microg once daily (FP200QD) or placebo. RESULTS: BD patients treated with FP100BID, FP200QD, and placebo had mean increases in FEV(1) from baseline to end point of 0. 49 L, 0.37 L, and 0.21 L, respectively (P <.001, FP100BID vs placebo; P =.05, FP200QD vs placebo). ICS patients treated with FP100BID and FP200QD had mean increases in FEV(1) of 0.27 L and 0.11 L, respectively, compared with a decrease in FEV(1) of -0.08 L with placebo (P <.001, FP100BID vs placebo; P =.023, FP200QD vs placebo). BD patients treated with FP100BID and FP200QD had mean increases in morning peak expiratory flow from baseline to end point of 31 L/min and 27 L/min, respectively, compared with a 1 L/min increase in patients treated with placebo. ICS patients treated with FP100BID had a mean increase in morning peak expiratory flow (from baseline to end point) of 18 L/min compared with mean decreases of -3 L/min and -12 L/min in the FP200QD and placebo groups, respectively. More patients were withdrawn from placebo (26% and 48%, in BD and ICS patients, respectively) than from fluticasone propionate (7%-9% [BID-QD] and 18%-32% [BID-QD], in BD and ICS patients, respectively) because of failure to meet predetermined asthma stability criteria. CONCLUSION: The efficacies of FP100BID and FP200QD were comparable with regard to improvement in pulmonary function and asthma stability in BD patients. In ICS patients, asthma control was maintained with FP200QD, whereas FP100BID provided greater improvements in pulmonary function and asthma stability.

Administration, Inhalation↗
PubMed2000

Limiting long-term illness among black Caribbeans, black Africans, Indians, Pakistanis, Bangladeshis and Chinese born in the UK.

AIM: To examine limiting long-term illness among ethnic groups born in the UK. DESIGN: Study members in the ONS Longitudinal Study, a representative 1% sample of England and Wales, present at the 1991 Census were examined. Socio-economic position was measured using housing tenure and access to cars. MAIN RESULTS: Black Caribbeans, Black Africans, Indians, Pakistanis and Bangladeshis reported more limiting long-term illness than whites, and the Chinese less. The level was higher among Black Africans than Black Caribbeans, even after adjustment for socio-economic position. Corresponding patterns were seen across the generations for all groups except Black Africans. Black Africans born in the UK reported more limiting long-term illness than did those born in Africa. Adjusting for socio-economic position lowered the risks in every group except Indians. The effect was strongest for Black Caribbeans, among whom adjustment removed the higher risks, and Bangladeshis, among whom the higher risks were no longer significant. CONCLUSION: For South Asians and Black Caribbeans poor health persisted across generations, and for Black Africans health worsened. There are over 1.5 million second- and third-generation migrants in these ethnic groups, but little is known about the consequences of having a multigenerational identity.

Africa↗
PubMed1999

Effects of naltrexone and fluoxetine on alcohol self-administration and reinstatement of alcohol seeking induced by priming injections of alcohol and exposure to stress.

We have recently shown that priming injections of alcohol and footshock stress reinstate alcohol seeking in drug-free rats. Here we tested whether naltrexone and fluoxetine, two drugs used in the treatment of alcohol dependence, would affect reinstatement of alcohol seeking induced by these events. We also determined the effects of these drugs on alcohol self-administration during the maintenance phase. Rats were trained to press a lever for a 12% w/v alcohol solution. After stable drug-taking behavior was obtained, lever pressing for alcohol was extinguished. Reinstatement of drug seeking was then determined after priming injections of alcohol (0.24-0.96 g/kg) or exposure to intermittent footshock (5 and 15 min). Rats were pretreated with naltrexone (0.2-0.4 mg/kg) or fluoxetine (2.5-5 mg/kg) during maintenance or during tests for reinstatement. Both naltrexone and fluoxetine decreased lever presses for alcohol during the maintenance phase. Naltrexone blocked alcohol-induced, but not stress-induced reinstatement. In contrast, fluoxetine blocked stress-induced reinstatement, while its effect on alcohol-induced reinstatement was less consistent. The implications of these data to the understanding of relapse to alcohol are discussed.

Alcohol Deterrents↗
PubMed1999

Dinucleotide repeat polymorphisms in EDN1 and NOS3 are not associated with severe diabetic retinopathy in type 1 or type 2 diabetes.

PURPOSE: Endothelin-1, and constitutive endothelial nitric oxide synthase, have been implicated in the pathogenesis of diabetic retinopathy. We therefore screened polymorphisms within the genes encoding these two vasoactive agents in a sample of individuals with 15 years of diabetes and no retinopathy (ETDRS level 10 or better) and those with severe retinopathy (ETDRS level 50 or worse). METHODS: PCR primers for highly polymorphic sites within the EDN1 and NOS3 genes were used to genotype individuals with type 1 or type 2 diabetes with severe or no retinopathy. Allele frequencies were compared between groups using chi-squared analysis and adjusting for multiple comparisons. RESULTS: No significant differences were observed in allele frequencies for these two markers between the patients who had retinopathy and the patients who did not. CONCLUSION: Polymorphic variability in the EDN1 and NOS3 genes does not appear to have a major impact on determining susceptibility or resistance to diabetic retinopathy.

Adult↗
PubMed1999

Genotyping and functional analysis of a polymorphic (CCTTT)(n) repeat of NOS2A in diabetic retinopathy.

Accumulating evidence shows that the severity and rapidity of onset of diabetic retinopathy are influenced by genetic factors. Expression of the nitric oxide synthases is altered in the retinal vasculature in the early stages of diabetic retinopathy. We analyzed the allele distribution of a polymorphic pentanucleotide repeat within the 5' upstream promoter region of the NOS2A gene in samples of diabetic patients. In diabetic patients from Northern Ireland, the 14-repeat allele of the NOS2A marker was significantly associated with the absence of diabetic retinopathy. Carriers of this repeat had 0.21-fold the relative risk of developing diabetic retinopathy than noncarriers of this allele. They also had significantly fewer renal and cardiovascular complications. The ability of differing numbers of (CCTTT)(n) pentanucleotide repeats to induce transcription of the NOS2A gene was analyzed using a luciferase reporter gene assay in transfected colonic carcinoma cells. Interleukin 1beta (IL-1beta) induction was most effective in constructs carrying the 14-repeat allele. When cells were incubated in 25 mM glucose to mimic the diabetic state, IL-1beta induction was inhibited in all cases, but to a significantly lesser extent with the 14-repeat allele. These unique properties of the 14-repeat allele may confer selective advantages in diabetic individuals, which may delay or prevent microvascular complications of diabetes.

Adult↗
PubMed1999

Does social mobility affect the size of the socioeconomic mortality differential?: evidence from the Office for National Statistics Longitudinal Study.

"The effect of social mobility on the socioeconomic differential in mortality is examined with data from the Office for National Statistics Longitudinal Study. The analyses involve 46,980 men aged 45-64 years in 1981. The mortality risk of the socially mobile is compared with the mortality risk of the socially stable after adjustment for their class of origin (their social class in 1971) and class of destination (their social class in 1981) separately. Among those in employment there is some evidence that movement out of their class of origin is in the direction predicted by the idea of health-related social mobility. This evidence, however, seems strongest for causes of death which are least likely to have been preceded by prolonged incapacity. Movement into the class of destination, however, shows the opposite relationship with mortality."

Age Factors↗
PubMed1999

Occupational class and ischemic heart disease mortality in the United States and 11 European countries.

OBJECTIVES: Twelve countries were compared with respect to occupational class differences in ischemic heart disease mortality in order to identify factors that are associated with smaller or larger mortality differences. METHODS: Data on mortality by occupational class among men aged 30 to 64 years were obtained from national longitudinal or cross-sectional studies for the 1980s. A common occupational class scheme was applied to most countries. Potential effects of the main data problems were evaluated quantitatively. RESULTS: A north-south contrast existed within Europe. In England and Wales, Ireland, and Nordic countries, manual classes had higher mortality rates than nonmanual classes. In France, Switzerland, and Mediterranean countries, manual classes had mortality rates as low as, or lower than, those among nonmanual classes. Compared with Northern Europe, mortality differences in the United States were smaller (among men aged 30-44 years) or about as large (among men aged 45-64 years). CONCLUSIONS: The results underline the highly variable nature of socioeconomic inequalities in ischemic heart disease mortality. These inequalities appear to be highly sensitive to social gradients in behavioral risk factors. These risk factor gradients are determined by cultural as well as socioeconomic developments.

Adult↗
PubMed1999

The potential to identify South Asians using a computerised algorithm to classify names.

Ethnic studies are limited by the lack of information on ethnic origin in data sources. This paper examines a computerised approach to identify South Asians by names. Computerised analysis of names is not an ideal solution, but it helps to solve the methodological difficulty of identifying South Asians, particularly in historical administrative datasets where self-assessed ethnicity is not possible and visual inspection is too time consuming and prone to errors. This approach, though useful, is limited to groups easily distinguishable by name and the collection of information on ethnicity should remain the aim in the long-term.

Adult↗
PubMed1998

The reduction in alcohol intake in rats by isoproterenol is attenuated by indomethacin but not enalapril: relationship to blood glucose levels.

Many adrenergic agonists including isoproterenol, a beta1,2-adrenergic agonist, reduce alcohol consumption, but the mechanism of this effect is not known. Adrenergic agonists have a variety of effects, among which are their ability to raise both angiotensin (ANG) II activity and plasma glucose levels. Previous research has shown that ANG II and enhanced glucose levels are accompanied by reductions in alcohol intake. Therefore, the following experiments assessed the roles of each of these factors in the suppression of alcohol intake by isoproterenol. Male Wistar rats were trained to drink a quantity of 6% (w/v) alcohol using the limited access procedure, which offers a daily 40-min access to alcohol and water. In experiment 1, isoproterenol or vehicle was administered s.c. just prior to alcohol availability, and only the group receiving isoproterenol showed a marked reduction in alcohol intake. Following this, the groups were pretreated i.p. with either vehicle or ascending doses of the prostaglandin synthetase inhibitor, indomethacin (2, 4 mg/kg), followed by either isoproterenol or vehicle. Control groups received either two vehicle injections or vehicle and indomethacin. Indomethacin alone did not affect alcohol intake at any of the doses tested but did dose-dependently attenuate the reduction in alcohol intake produced by isoproterenol. In experiment 2, isoproterenol was administered just prior to alcohol availability and when the suppression of alcohol intake stabilized, ascending doses of the angiotensin converting enzyme inhibitor, enalapril (1, 20, 40 mg/kg), were given i.p. 1 h prior to the isoproterenol. Enalapril altered water intake but had no effect on the isoproterenol-induced reduction in alcohol intake. These results show that the inhibition of alcohol drinking by isoproterenol varies more closely with altered glucose levels than with increased ANG II synthesis. They also demonstrate that downstream consequences of a drug may play a role in its effect on alcohol intake.

Adrenergic beta-Agonists↗
PubMed1998

Mortality of migrants from outside England and Wales by marital status.

It is well known that men and women who are married have lower mortality rates than those who are not. It is also known that some migrants from abroad have higher mortality rates than people in England and Wales and that they have different patterns of family formation and dissolution. In this article the authors investigate the patterns of mortality by country of birth, marital status and cause of death to see if the overall differences in mortality among migrants can be explained by their different marital patterns.

Adult↗
PubMed1998

Research implications of improvements in access to the ONS Longitudinal Study.

In this article we outline significant changes in the way the ONS Longitudinal Study data are stored, accessed and analysed. The data were held previously on mainframe computers. Recent technological changes have made it possible to introduce PC-based systems without compromising confidentiality. The advantages of this new computing environment are illustrated with recent findings on geographic inequalities in health.

Adolescent↗
PubMed1998

Longitudinal study of socio-economic differences in the incidence of stomach, colorectal and pancreatic cancers.

Using the ONS Longitudinal Study, the incidence of stomach, colorectal and pancreatic cancers from 1976-90 was examined for men and women aged 30 years and over by their housing tenure and occupational social class. Large socio-economic differences in the incidence of stomach cancer for both men and women were found. The pattern of colorectal cancer was less clear, with women in more advantaged social groups experiencing higher incidence while for men there was no significant association. Pancreatic cancer showed no association with socio-economic status. Consistent findings with each indicator strengthen the interpretation of the results. Risk factors for these cancers are known to vary by socio-economic status, and this study demonstrates the importance of continued monitoring of the distribution of cancer incidence.

Adult↗