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1.  Tumour necrosis factor (TNFα) as a novel therapeutic target in symptomatic corticosteroid dependent asthma 
Thorax  2005;60(12):1012-1018.
Background: Tumour necrosis factor α (TNFα) is a major therapeutic target in a range of chronic inflammatory disorders characterised by a Th1 type immune response in which TNFα is generated in excess. By contrast, asthma is regarded as a Th2 type disorder, especially when associated with atopy. However, as asthma becomes more severe and chronic, it adopts additional characteristics including corticosteroid refractoriness and involvement of neutrophils suggestive of an altered inflammatory profile towards a Th1 type response, incriminating cytokines such as TNFα.
Methods: TNFα levels in bronchoalveolar lavage (BAL) fluid of 26 healthy controls, 42 subjects with mild asthma and 20 with severe asthma were measured by immunoassay, and TNFα gene expression was determined in endobronchial biopsy specimens from 14 patients with mild asthma and 14 with severe asthma. The cellular localisation of TNFα was assessed by immunohistochemistry. An open label uncontrolled clinical study was then undertaken in 17 subjects with severe asthma to evaluate the effect of 12 weeks of treatment with the soluble TNFα receptor-IgG1Fc fusion protein, etanercept.
Results: TNFα levels in BAL fluid, TNFα gene expression and TNFα immunoreative cells were increased in subjects with severe corticosteroid dependent asthma. Etanercept treatment was associated with improvement in asthma symptoms, lung function, and bronchial hyperresponsiveness.
Conclusions: These findings may be of clinical significance in identifying TNFα as a new therapeutic target in subjects with severe asthma. The effects of anti-TNF treatment now require confirmation in placebo controlled studies.
PMCID: PMC1747263  PMID: 16166100
2.  Epithelial expression and release of FGF-2 from heparan sulphate binding sites in bronchial tissue in asthma 
Thorax  2004;59(7):557-562.
Background: The most characteristic structural change evident in endobronchial biopsies in asthma, even in mild disease, is subepithelial collagen deposition within the lamina reticularis. This has been associated with progressive loss of lung function and the persistence of airway hyperresponsiveness, and has been linked to airway fibroblast proliferation. A potent fibroproliferative factor in bronchoalveolar lavage fluid in asthma is fibroblast growth factor-2 (FGF-2). FGF-2 is a member of a family of heparin binding growth factors that bind to heparan sulphate proteoglycans (HSPG), an important determinant of FGF-2 activity. This study compared the level of expression and distribution of FGF-2 in relation to HSPG in bronchial tissue from normal and asthmatic subjects.
Methods: The distribution of FGF-2 and HSPG in intact and cleaved forms in endobronchial biopsies from normal and asthmatic subjects was examined using an immunohistochemical approach. A novel ELISA based method was developed to detect solubilisation of FGF-2 following addition of heparin and heparitinase to bronchial tissue slices.
Results: Immunohistochemical analysis showed that FGF-2 was co-localised to HSPG in epithelial and endothelial basement membranes. Epithelial FGF-2, but not HSPG, was significantly more abundant in patients with mild asthma than in normal subjects. In vitro experiments indicated that FGF-2 was released from binding sites in the tissue by heparin and heparitinase I.
Conclusions: FGF-2 is bound by HSPG in bronchial tissue. The mast cell, through the release of heparin and endoglycosidase, may make a unique contribution to tissue remodelling in allergic asthma.
PMCID: PMC1747073  PMID: 15223860
3.  Does the disbursement of income increase psychiatric emergencies involving drugs and alcohol? 
Health Services Research  2000;35(4):813-823.
OBJECTIVE: To determine if the incidence of psychiatric emergencies involving drugs or alcohol supports the argument that mentally ill persons contribute to elevated mortality during the days following disbursement of private earnings and public income transfers. STUDY DESIGN: Interrupted time-series using Box-Jenkins methods. DATA COLLECTION/EXTRACTION METHODS: Daily counts of adults admitted to psychiatric emergency services in San Francisco after using drugs or alcohol were derived from medical records for the period January 1 through June 30, 1997. PRINCIPAL FINDINGS: Psychiatric emergencies among males who had used drugs or alcohol were elevated in the early days of the month. Such emergencies among females were not similarly elevated. Emergencies among females who had not used drugs or alcohol were elevated in the early days of the month. CONCLUSION: Elevated mortality in the first week of the month may be attributable, in part, to the "check effect" or use of drugs and alcohol by mentally ill males in the days after they receive income. The contribution of women is more complex and may be induced by drug or alcohol abuse among persons in their social networks. The check effect suggests that persons with a history of substance abuse and mental illness should be offered the opportunity to have their income managed by someone who can monitor and influence how the money is being spent. The fact that drug- or alcohol-related admissions among males exhibit temporal patterns suggests that the provision of preventive as well as treatment services may be strategically scheduled.
PMCID: PMC1089154  PMID: 11055450
4.  Expanding access to coronary artery bypass surgery: who stands to gain? 
British Heart Journal  1995;73(2):129-133.
OBJECTIVE--To determine the perceptions of general practitioners (GPs) about the benefits of coronary artery bypass surgery, in terms of gains in life expectancy, for different groups of patients. DESIGN--A questionnaire survey of all GPs in Northern Ireland. SETTING--A survey conducted collaboratively by the departments of public health medicine in each of the four health boards in the province, serving a total population of 1.5 million. MAIN OUTCOME MEASURES--The median and mean gain in life expectancy perceived by groups of doctors for smoking and non-smoking male and female 55 year old patients. The percentage of 50 year old and 70 year old non-smoking patients considered likely to have their lives extended with bypass surgery. Differences were assessed using the Mann-Whitney U test for unpaired samples and the Wilcoxon signed rank tests for paired. RESULTS--541 GPs replied (response rate 56%). The median (and mean) perceived gain in life expectancy after cardiac surgery for non-smoking 55 year old subjects was 120 (104) months for men and 120 (112) months for women (z = 6.42; P < 0.0001; Wilcoxon signed rank test). For male and female smokers of the same age, the perceived gains were 48 (47) and 60 (52) months respectively (z = 6.72; P < 0.0001; Wilcoxon signed ranks test), both figures being significantly different than for non-smokers. The median (and mean) percentage of patients that the doctors considered would have their lives extended by bypass surgery was 70 (64) of every 100 "young" patients and 40 (42) of every 100 "old" patients, (z = 16.2; P < 0.0001). CONCLUSIONS--These results point to a significant overestimation of the benefits of coronary artery bypass surgery by GPs in Northern Ireland and to a need to develop guidelines for referral.
PMCID: PMC483778  PMID: 7696021
5.  Is choice of general practitioner important for patients having coronary artery investigations? 
Quality in Health Care  1994;3(1):17-22.
OBJECTIVE--To determine whether particular sociodemographic characteristics of patients with stable angina affected their general practitioners' (GPs') decisions to refer them for revascularisation assessment. DESIGN--Postal questionnaire survey. SETTING--Collaborative survey by the departments of public health medicine in each of the four health boards in Northern Ireland, serving a total population of 1.5 million. SUBJECTS--All (962) GPs. MAIN MEASURES--The relation between GPs' referral decisions and patients' age, sex, employment status, home circumstances, smoking habits, and obesity. RESULTS--541 GPs replied (response rate 56%). Most were "neutral" towards a patient's sex (428, 79%), weight (331, 61%), smoking habit (302, 56%), employment status (431, 80%), and home circumstances (408, 75%) in making decisions about referral. In assigning priority for surgery most were neutral towards the patient's sex (459, 85%), employment status (378, 70%), and home circumstances (295, 55%). However, most GPs (518, 95%) said that younger patients were more likely to be referred, and a significant minority were less likely to refer patients who smoked (202, 37%) and obese patients (175, 32%) and more likely to refer employed patients (97, 18%) and those with dependents (117, 22%) (compared with patients with otherwise comparable clinical characteristics); these views paralleled the priority which GPs assigned these groups. The stated likelihood of referral of young patients was independent of the GPs' belief in ability to benefit from revascularisation, but propensity to refer and perception of benefit were significantly associated for all other patient characteristics. CONCLUSION--GPs' weighting of certain characteristics in reaching decisions about referral for angiography is not uniform and may contribute to unequal access to revascularisation services for certain patient groups.
PMCID: PMC1055177  PMID: 10136255
6.  Cellular fatty acid composition of Campylobacter pylori from primates and ferrets compared with those of other campylobacters. 
Journal of Clinical Microbiology  1989;27(5):938-943.
The cellular fatty acid profiles of newly described campylobacters were determined on a polar, capillary column. Six isolates of the gastric spiral organism, Campylobacter pylori subsp. mustelae, from ferrets from Australia, England, and the United States were all found to have a similar fatty acid profile which was different from that of C. pylori from humans; C. pylori subsp. mustelae did not have 3-hydroxyoctadecanoic acid (3-OH C18:0) and had much less tetradecanoic acid (C14:0) and much more hexadecanoic acid (C16:0). Inasmuch as Lambert et al. (M.A. Lambert, C.M. Patton, T.J. Barrett, and C.W. Moss, J. Clin. Microbiol. 25:706-713, 1987) have proposed that campylobacters can be grouped by cellular fatty acid composition, we propose this organism should be in a new gas-liquid chromatography (GLC) group, group J. Seven isolates of gastric spiral organisms from macaque monkeys and baboons, including three from Macaca nemestrina, and one isolate from a pig were found to have fatty acid profiles very similar to that of C. pylori; but a second type of organism (type B) from M. nemestrina had a unique profile without 19-carbon cyclopropane fatty acid (C19:0 cyc) but with 3-hydroxy tetradecanoic acid (OH C14:0), which is not present in other gastric spiral bacteria. We propose that this organism (nemestrina type B) should be in a new GLC group, group K. The cellular fatty acid profile of seven isolates of C. jejuni subsp. doylei was found to be similar to that for C. jejuni, but with possibly significant differences in that the former did not have 3-OH C14:0 but did have 3-hydroxyhexadecanoic acid (3-OH C16:0) and had more C14:0 than did C. jejuni. Two strains of urease-positive thermophilic campylobacters were found to have a profile similar to that of "C. cinaedi" and thus should be included with them in GLC group D. We confirm that C. sputorum has a unique cellular fatty acid composition and suggest that it should be in a new group, group H.
PMCID: PMC267458  PMID: 2745703
7.  Measles in the Southern Health Board--implications for resources. 
During a recent epidemic of measles in the Southern Health and Social Services Board in Northern Ireland it became apparent that the level of notifications of measles by general practitioners did not reflect the true incidence of the disease at that time. In trying to establish a more accurate measure of the incidence of measles it became clear that much money and manpower had been used to treat this outbreak. We tried to cost a defined period covering 1 January to 30 June 1983 to draw attention to the possible benefits of a more effective measles vaccination programme in preventing disease and saving resources. The implications of our present poor rate of vaccination were measured for hospital services, primary medical care services, and related consequences. The costs for the defined period were approximately pounds 175 931, and if the outcome had been worse in a few cases it might have been as high as pounds 1 375 931.
PMCID: PMC1442101  PMID: 6430445
8.  Possible method of identifying spotter practices in a health board in Northern Ireland. 
We examined the notification of infectious diseases, including measles, by general practitioners over 18 months, which included a measles epidemic in the area covered by the Southern Health and Social Services Board in Northern Ireland. Of the 156 general practitioners who provided services in the area, 27 (17.3%) had a pattern of notification which might render them acceptable as "spotter" practices, a system which at present does not exist in Northern Ireland, although it is used in the rest of the United Kingdom. In future we hope to be able to; (i) predict impending epidemics of infectious disease; (ii) mobilise Health Service resources to minimise the effects of such epidemics; (iii) monitor the effects of improving the level of uptake of measles vaccine.
PMCID: PMC1444748  PMID: 6419967
13.  General Anaesthesia for Dental Surgery 
Postgraduate Medical Journal  1948;24(276):533-538.
PMCID: PMC2529848  PMID: 18888919
British Medical Journal  1937;2(4002):591-593.
PMCID: PMC2087312  PMID: 20780915

Results 1-14 (14)