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Biomedical subjects

G Higgs

Publications and source records attributed to G Higgs.

15 recordsLinked to original sources
PubMed2005

Reasons for tooth extraction in four general dental practices in South Wales.

Tooth retention has been one of the main aims of oral care which in turn could have contributed to the social oral health divide. To investigate this issue further, data collected for a group audit was used to study the reasons for tooth extraction for patients attending for routine treatment at four dental practices. The practices served populations in areas with different levels of deprivation in South Wales. In 558 teeth extracted over 417 visits, the reasons for extractions were: caries 59%, periodontal disease 29.1%, pre-prosthetic 1%, wisdom teeth 4.6%, orthodontic 5.5%, trauma 1.2%, patient request 2.4% and 6.2% other reason. The number of extraction visits per day within the group of dental surgeons varied with three practitioners performing more than three extraction visits per day while one practitioner had only 0.51. These reasons did not significantly depend on levels of deprivation. However, significantly more teeth were extracted for caries in the most deprived group in comparison to the least deprived. Therefore, could there be a case for appropriate extractions in the quest for equitable care?

Adolescent↗
PubMed2004

Enumeration of Escherichia coli O157 in cattle faeces using most probable number technique and automated immunomagnetic separation.

AIMS: To determine the numbers of Escherichia coli O157 present in the faeces of naturally infected cattle. METHODS AND RESULTS: A combination of the most probable number (MPN) technique and automated immunomagnetic separation (AIMS) was used to enumerate E. coli O157 in cattle faeces from both pasture-fed and grain-fed animals. A total of 22 E. coli O157 positive faecal samples were enumerated for E. coli O157 (10 from pasture-fed and 12 from grain-fed animals). The numbers of E. coli O157 in cattle faeces varied from undetectable (<3 MPN g-1 of faeces) to 2.4 x 104 MPN g-1. There was no significant difference (P = 0.06) between the numbers of E. coli O157 in pasture-fed or grain-fed cattle faeces, although the geometric mean (antilog of the mean of log10 transformed MPN values) was higher in grain-fed (130 MPN g-1) than in pasture-fed (13 MPN g-1). CONCLUSIONS: Although the number of samples tested is small, the results indicate that E. coli O157 make up a small proportion of the total E. coli population present in cattle faeces. SIGNIFICANCE AND IMPACT OF THE STUDY: Information on the numbers of E. coli O157 present in cattle will assist in developing more robust quantitative risk assessments and formulating intervention strategies.

Animal Feed↗
PubMed2004

The prevalence and concentration of Escherichia coli O157 in faeces of cattle from different production systems at slaughter.

AIMS: To determine the prevalence and concentration of Escherichia coli O157 shed in faeces at slaughter, by beef cattle from different production systems. METHODS AND RESULTS: Faecal samples were collected from grass-fed (pasture) and lot-fed (feedlot) cattle at slaughter and tested for the presence of E. coli O157 using automated immunomagnetic separation (AIMS). Escherichia coli O157 was enumerated in positive samples using the most probable number (MPN) technique and AIMS and total E. coli were enumerated using Petrifilm. A total of 310 faecal samples were tested (155 from each group). The geometric mean count of total E. coli was 5 x 10(5) and 2.5 x 10(5) CFU g(-1) for lot- and grass-fed cattle, respectively. Escherichia coli O157 was isolated from 13% of faeces with no significant difference between grass-fed (10%) and lot-fed cattle (15%). The numbers of E. coli O157 in cattle faeces varied from undetectable (<3 MPN g(-1)) to 1.1 x 10(5) MPN g(-1). Twenty-six (67%) of 39 O157 positive faeces had <10 MPN g(-1) and three (8%) had counts between 10(3)-10(5) MPN g(-1). There was no significant difference between concentrations of E. coli O157 in the faeces of grass-fed or lot-fed cattle. CONCLUSION: The prevalence and numbers of E. coli O157 in the faeces of cattle at slaughter were not affected by the production systems evaluated in this study. SIGNIFICANCE AND IMPACT OF THE STUDY: Information on the prevalence and numbers of E. coli O157 can be used for formulating intervention strategies and in quantitative risk assessments.

Abattoirs↗
PubMed2004

Quantification and prevalence of Salmonella in beef cattle presenting at slaughter.

AIMS: A survey to determine the prevalence and numbers of Salmonella in beef cattle presented for slaughter at abattoirs across Australia was conducted between September 2002 and January 2003. METHODS AND RESULTS: Automated immunomagnetic separation (AIMS) was used for detection and isolation of Salmonella enriched from cattle faeces. Salmonella were enumerated from positive samples using a combination of the Most Probable Number (MPN) technique and AIMS. A total of 310 faecal samples were tested, 155 were from lot-fed cattle and 155 from grass-fed cattle. Salmonella spp. were isolated from 21 (6.8%) of the cattle and the prevalence amongst grass-fed cattle (4.5%) was not significantly different to that found in lot-fed cattle (9%). Counts of Salmonella in positive faeces varied from <3 MPN g(-1) of faeces to 2.8 x 10(3) MPN g(-1) and 71% of positive samples had counts <10 MPN g(-1) faeces. There was no significant difference in the mean log10 number of Salmonella in faeces of cattle from each production system. CONCLUSION: Low numbers of beef cattle were found to shed Salmonella at the time of slaughter and the prevalence and the associated faecal concentrations did not vary significantly with the pre-slaughter production system (grass or lot feeding). The faecal concentration of Salmonella in the majority of faeces was low (<10 MPN g(-1)) with few high concentrations up to 3 x 10(3) MPN g(-1), suggesting there may be a low risk of carcase contamination. SIGNIFICANCE AND IMPACT OF THE STUDY: Beef cattle do not appear to be a major source of entry of Salmonella into the human food chain and the quantitative information contained in this study can be used in quantitative assessments of the associated risk of human salmonellosis.

Abattoirs↗
PubMed2002

CDP840. A prototype of a novel class of orally active anti-inflammatory phosphodiesterase 4 inhibitors.

The discovery, synthesis and biological activity of a series of triarylethane phosphodiesterase 4 inhibitors is described. Structure-activity relationship studies are presented for CDP840 (29), a potent, chiral, selective inhibitor of PDE 4 (IC(50) 4nM). CDP840 is non-emetic in the ferret at 30mgkg(-1) (po), active in models of inflammation and reverses ozone-induced bronchial hyperreactivity in the guinea pig.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2001

Is there a role for GIS in the 'new NHS'?

In this paper we draw on the existing literature to highlight the gap between academic health-based applications of Geographical Information Systems (GIS) and their everyday use within the UK National Health Service (NHS). We provide examples of the operational benefits accruing from using GIS in a range of health care applications whilst acknowledging the limited use of such technologies in strategic health tasks. The implications of recent policy changes for future projected use of such systems are discussed before presenting a research agenda for realising GIS potential within the NHS. The paper concludes by re-emphasising the importance of using GIS in strategic health planning contexts in the light of both recent health-care restructuring and new technological developments in the health service.

Delivery of Health Care↗
PubMed2000

Urban-rural mortality differentials: controlling for material deprivation.

This paper investigates the relationship between premature mortality and material deprivation, and the differences in this relationship between urban and rural areas. We examine, given comparable measures of affluence or deprivation, whether residual differences exist between urban and rural areas for all-causes of death and, separately, for cancers, circulatory and respiratory diseases. Using 1990-92 mortality data for the 908 wards of Wales we apply statistical analyses based on tabular data and parametric Poisson regression models. Contrasts are sought between six urban and rural categories defined in terms of settlement sizes and the employment structure of rural areas. Inequalities in all-cause premature mortality are widest in the cities, narrowest in the deeper rural areas, and of intermediate and comparable value in other areas of Wales. This is largely a reflection of the different distributions of material deprivation in these areas. After controlling for differences in socio-economic characteristics, using deprivation measures, the tendency for lower mortality in deeper rural areas is substantially reduced. Residual mortality differences between urban and rural areas are shown to be dependent on the way deprivation is measured and the disease group under study. For cancers there are no residual mortality differences, while for respiratory and circulatory diseases some of the residual variation can be accounted for by employment variables, particularly previous employment in the coal mining industry.

Humans↗
PubMed1998

Spatial and temporal variation of mortality and deprivation 2: statistical modelling.

"Building on the tabular analyses exemplified in our first paper and widely used in the medical literature, we use generalised linear models to provide a formal, statistical approach to the analysis of mortality and deprivation relationships, and their change over time. Three types of fixed effects model are specified and estimated with the same ward-level data sets for Wales examined in our first paper. They are: Poisson models for analysing mortality and deprivation at a single cross section in time; repeated-measures Poisson models for analysing mortality-deprivation relations, not only at cross sections in time, but also their changes over time; and logit models focusing on temporal changes in mortality-deprivation relationships. Nonlinear effects of deprivation on mortality have been explored by using dummy variables representing deprivation categories to establish the connection between formal statistical models and the tabular approach"

Demography↗
PubMed1998

Spatial and temporal variation of mortality and deprivation. 1: widening health inequalities.

"In this paper we examine the relationship between premature mortality and material deprivation both over time (the intercensal period, 1981-91) and over space (for the population in wards and ward groups in Wales). Our focus is on the methods of analysis for small area...multiple cross-section mortality data and their application to the substantive issue of the persistent and widening inequalities in Wales.... We examine all-cause deaths and mortality by specific disease classes for groups (quintiles) of wards ranked according to standard measures of material deprivation. Although there have been reductions in premature mortality across all deprivation groups in Wales, over the decade, the gap has widened between the most and least deprived areas."

Demography↗
PubMed1996

The inhibition of antigen-induced eosinophilia and bronchoconstriction by CDP840, a novel stereo-selective inhibitor of phosphodiesterase type 4.

1. The novel tri-aryl ethane CDP840, is a potent and selective inhibitor of cyclic AMP phosphodiesterase type 4 (PDE 4) extracted from tissues or recombinant PDE 4 isoforms expressed in yeast (IC50S: 4-45 nM). CDP840 is stereo-selective since its S enantiomer (CT 1731) is 10-50 times less active against all forms of PDE 4 tested while both enantiomers are inactive (IC50S: > 100 microM) against PDE types 1, 2, 3 and 5. 2. Oral administration of CDP840 caused a dose-dependent reduction of interleukin-5 (IL-5)-induced pleural eosinophilia in rats (ED50 = 0.03 mg kg-1). The eosinophils in pleural exudates from CDP840-treated animals contained higher levels of eosinophil peroxidase (EPO) than cells from control animals, suggesting a stabilizing effect on eosinophil degranulation. CDP840 was approximately equi-active with the steroid dexamethasone in this model and was 10-100 times more potent than the known PDE 4-selective inhibitors rolipram and RP73401. The activity of CDP840 was not influenced by adrenalectomy, beta-sympathomimetics or beta-sympatholytics. 3. Antigen-induced pulmonary eosinophilia in sensitized guinea-pigs was reduced dose-dependently by CDP840 (0.01-1 mg kg-1, i.p.) and intracellular EPO levels were significantly higher. CDP840 was more potent in these activities than CT1731 or rolipram and comparable in potency to RP73401. 4. Rolipram or CDP840 were less active than dexamethasone in preventing neutrophil accumulation, or exudate formation in carrageenan-induced pleurisy in rats and thus do not exhibit general anti-inflammatory activity. 5. In sensitized guinea-pigs, aerosols of the antigen ovalbumin caused a dose-dependent bronchoconstriction demonstrated by an increase in pulmonary inflation pressure. Administration of CDP840 (0.001-1.0 mg kg-1, i.p.), 1 h before antigen challenge, resulted in dose-dependent reduction in response to antigen. This activity was not due to bronchodilatation since higher doses of CDP840 (3 mg kg-1) did not significantly change the bronchoconstrictor response to histamine. Rolipram was approximately 10 times less active than CDP840 in preventing antigen-induced bronchoconstriction. 6. These results confirm the observations that selective PDE 4 inhibitors reduce antigen-induced bronchoconstriction and pulmonary eosinophilic inflammation. CDP840 is more potent than rolipram in inhibiting native or recombinant PDE 4. Unlike the recently described potent PDE 4 inhibitor RP73401, CDP840 is more active than rolipram in the rat IL-5 model following oral administration. The novel series of tri-aryl ethanes, of which CDP840 is the lead compound, could be the basis of an orally active prophylactic treatment for human asthma.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1996

Inhibition of bronchospasm and ozone-induced airway hyperresponsiveness in the guinea-pig by CDP840, a novel phosphodiesterase type 4 inhibitor.

1. The activity of CDP840, a novel, potent and selective cyclic nucleotide phosphodiesterase type 4 (PDE 4) inhibitor, was evaluated in guinea-pig models (in vitro and in vivo) of bronchospasm, ozone-induced airway hyperresponsiveness (AHR) and non-cholinergic bronchoconstriction. Comparisons were made with (i) other PDE 4 inhibitors: CT1731 (S-enantiomer of CDP840), rolipram, RP73401 and (ii) the clinically used agents salbutamol and theophylline. 2. CDP840 relaxed isolated trachea, under basal tone (EC50 4.5 +/- 1.1 microM) being 17 fold less potent than rolipram (EC50 0.26 +/- 0.13 microM) but attaining the same Emax (83 +/- 6% of the response to 300 microM papaverine). 3. CDP840 relaxed tracheae pre-contracted with carbachol (IC25 39 +/- 9 microM) and histamine (IC25 4 +/- 1 microM) producing monophasic curves. Stereoselectivity was not observed with CT1731 against either carbachol (IC25 33 +/- 11 microM) or histamine (IC25 17 +/- 10 microM). Aminophylline was 1.6 fold (carbachol) and 11 fold (histamine) less potent than CDP840. Rolipram and RP73401 produced tri-phasic relaxation curves but were of similar potency (at the IC25 level) to CDP840 against carbachol (rolipram 18 +/- 5 microM, RP73401 39 +/- 1 microM) whereas against histamine they were approximately 20 fold more potent (rolipram 0.2 +/- 0.1 microM, RP73401 0.2 +/- 0.1 microM). In producing > 30% (carbachol) and > 60% (histamine) relaxation these inhibitors had similar potency and were poor compared to salbutamol. 4. Pre-incubation with CDP840 (10 microM) did not antagonize histamine-induced contraction of isolated trachea; however, it did cause a slight potentiation of the subsequent relaxation to salbutamol (IC50 23 +/- 1 to 15 +/- 2 nM). 5. Pretreatment (1 h) with either CDP840 (1 mg kg-1, i.p. or 3 mg kg-1, i.v.) or rolipram (1 mg kg-1, i.p.) did not bronchodilate or antagonize bronchospasm due to inhaled histamine in anaesthetized, ventilated guinea-pigs. Salbutamol (1 mg kg-1, i.p.) did not bronchodilate but caused a parallel 7 fold rightward shift in the histamine dose-response curve. 6. Stimulation of the vagus nerve in the presence of atropine resulted in a frequency-related bronchoconstriction. CDP840 and rolipram (i.v.) inhibited the response being approximately equipotent (EC50 approximately 10 micrograms kg-1). Neither drug inhibited bronchospasm to inhaled substance P. 7. CDP840 (1-10 micrograms kg-1 i.p.) dose relatedly inhibited ozone-induced bronchoconstriction. CT1731 (1 mg kg-1), rolipram (1 mg kg-1), RP73401 (10 micrograms kg-1) and aminophylline (10 mg kg-1) had no effect. Ozone-induced AHR to inhaled histamine was inhibited by CDP840 in a dose-related manner, 10 micrograms kg-1 abolishing the AHR. This effect was stereoselective as CT1731 was approximately 30 fold less potent than CDP840. Rolipram was approximately 100 fold less potent and RP73401 and aminophylline had no effect. CDP840 was orally active being approximately 10 fold less potent compared to i.p. administration. 8. CDP840 is a poor spasmolytic and anti-spasmogenic agent in response to exogenous mediators; however, it potently inhibits vagally mediated non-cholinergic bronchoconstriction and ozone-induced AHR to histamine. It is possible that regulation of cyclic AMP by PDE 4 contributes to neuronal sensitivity in the airways. Furthermore, CDP840 may suppress AHR without being an overt bronchodilator. Such a profile of activity may have therapeutic benefit in airways diseases such as asthma.

Analysis of Variance↗
PubMed1994

The in vivo and in vitro effects of antibodies against rabbit beta 2-integrins.

Beta 2-integrins play a crucial role in the development of an inflammatory response. In ours study, Abs have been used to investigate the role of individual members of this family of adhesion molecules in both in vivo and in vitro assays. An Ab against rabbit LFA-1 effectively inhibited the adhesion of rabbit polymorphonuclear leukocytes to rabbit endothelial cells in culture and was also effective in blocking cell recruitment to the peritoneum and vascular leakage at dermal sites of inflammation. An Ab that inhibited rabbit complement receptor type 3 function in vitro failed to inhibit cell recruitment to the peritoneum or vascular leakage in response to intradermal FMLP. Histologic studies suggested that the anti-complement receptor type 3 Ab may have modified the cell migration process.

Animals↗