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Biomedical subjects

F Kee

Publications and source records attributed to F Kee.

At least 19 recordsLinked to original sources
PubMed2006

Homocysteine and coronary heart disease risk in the PRIME study.

INTRODUCTION: Despite recent meta-analyses suggesting that homocysteine is an independent predictor of coronary heart disease (CHD), there is debate regarding whether elevated homocysteine may be deleterious only in the presence of other risk factors, with which it acts synergistically to exert a multiplicative effect on CHD risk, emerging only as a CHD predictor in patients with pre-existing risk factors. The Prospective Epidemiological Study of Myocardial Infarction (PRIME) Study is a multicentre prospective study of 10593 men from France and Northern Ireland, investigating cardiovascular risk factors. We investigated: (1) whether higher homocysteine is associated with increased CHD risk in the PRIME case-control cohort; (2) whether homocysteine interacts synergistically with pre-existing CHD risk factors. METHODS: Homocysteine was measured in 323 participants who had developed CHD at 5-year follow-up and in 638 matched controls. RESULTS: There was no significant difference in homocysteine between cases and controls (p=0.18). Homocysteine was significantly higher in current smokers (geometric mean mumol/l (interquartile range mumol/l) 9.45 (7.43, 11.75)) compared with non-smokers (8.90 (7.32, 10.70); p=0.007). There was a significant interaction between homocysteine, smoking and CHD risk (chi2=10.29, d.f.=2, p=0.006). CONCLUSIONS: These findings suggest that elevated homocysteine is significantly associated with CHD risk in current smokers.

Biomarkers↗
PubMed2005

Rheumatologists' judgements about the efficacy of anti-TNF therapy in two neighbouring regions.

OBJECTIVES: The requirement in Northern Ireland to prescribe biological agents according to National Institute for Clinical Excellence/British Society for Rheumatology (NICE/BSR) guidelines and within a fixed budget has created a waiting list for treatment that has no parallel in the Republic of Ireland. The study investigated the bearing this situation may have had on consultants' judgements in the respective areas. METHODS: Seventy-eight case vignettes created from the data on real patients with RA treated with biologicals in the north and south of Ireland were appraised by nine southern and eight northern consultants, who judged the clinical benefit and significance of the patients' condition after a trial of therapy. Quantitative (clinical judgement analysis) and qualitative (focus groups) techniques were used. RESULTS: Northern consultants perceived a slightly greater degree of clinical benefit after a trial of therapy than southern consultants. Judgement models of northern and southern consultants were broadly comparable. The latter tended to be more uniform in their judgements than the southern group. Focus group discussions with consultants largely validated the findings of the quantitative analysis but revealed how clinical judgement analysis might be misled by gaming strategies. CONCLUSIONS: Despite the absence of overt rationing in the south of Ireland, as far as the judgement of therapeutic benefit from biologicals was concerned, the clinical judgement policies of practitioners were very similar to those in the north. The adoption of NICE/BSR guidelines in the north may have improved the uniformity of clinical practice in Northern Ireland.

Antibodies, Monoclonal↗
PubMed2005

Demographic and temporal trends in out of hospital sudden cardiac death in Belfast.

OBJECTIVE: To determine the epidemiology of out of hospital sudden cardiac death (OHSCD) in Belfast from 1 August 2003 to 31 July 2004. DESIGN: Prospective examination of out of hospital cardiac arrests by using the Utstein style and necropsy reports. World Health Organization criteria were applied to determine the number of sudden cardiac deaths. RESULTS: Of 300 OHSCDs, 197 (66%) in men, mean age (SD) 68 (14) years, 234 (78%) occurred at home. The emergency medical services (EMS) attended 279 (93%). Rhythm on EMS arrival was ventricular fibrillation (VF) in 75 (27%). The call to response interval (CRI) was mean (SD) 8 (3) minutes. Among patients attended by the EMS, 9.7% were resuscitated and 7.2% survived to leave hospital alive. The CRI for survivors was mean (SD) 5 (2) minutes and for non-survivors, 8 (3) minutes (p < 0.001). Ninety one (30%) OHSCDs were witnessed; of these 91 patients 48 (53%) had VF on EMS arrival. The survival rate for witnessed VF arrests was 20 of 48 (41.7%): all 20 survivors had VF as the presenting rhythm and CRI < or = 7 minutes. The European age standardised incidence for OHSCD was 122/100,000 (95% confidence interval 111 to 133) for men and 41/100,000 (95% confidence interval 36 to 46) for women. CONCLUSION: Despite a 37% reduction in heart attack mortality in Ireland over the past 20 years, the incidence of OHSCD in Belfast has not fallen. In this study, 78% of OHSCDs occurred at home.

Adult↗
PubMed2005

Pre-hospital coronary care and coronary fatality in the Belfast and Glasgow MONICA populations.

BACKGROUND: The aim of this study was to describe and compare coronary event case fatality and care pathways in two defined populations with access to different models of pre-hospital care provision. METHODS: Secondary analysis of MONItoring of Trends and Determinants in CArdiovascular Disease (MONICA) population coronary event registers (1988, 1989, 1990, 1992 and 1993). RESULTS: Case fatality at 28 days following an acute coronary event was 6.5% greater in the Glasgow MONICA Project (GMP) population (46.7%) than in the Belfast MONICA Project (BMP) population (40.2%). Pre-hospital case fatality was 33.9% in the GMP population and 28.3% in the BMP population. These differences could not be fully explained by mobile coronary care unit (MCCU) responses in the BMP area. Initial care was provided in hospital for 28.3% of the BMP events and only 7.7% of the GMP events. Additional data collected by the Belfast and Glasgow MONICA investigators support a large difference between the median delay to main medical care in the BMP events (120 min) and the median delay to ward admission in the GMP area (220 min) at this time. CONCLUSIONS: Our findings suggest that the delay between coronary event onset and access to specialist coronary care was the most likely critical difference, irrespective of hospital-based MCCU provision in the BMP area. An established 'culture of early intervention' in Belfast may have been an important factor. As a large proportion of coronary event fatalities continue to occur outside hospital, there is a need to strengthen the evidence base underpinning the provision of appropriate skilled care and treatment at the earliest possible opportunity.

Adult↗
PubMed2004

Improved survival for melanoma in Northern Ireland: a comparison of two 5-year periods (1984-88 and 1994-98).

BACKGROUND: The incidence of cutaneous malignant melanoma has been rising steadily in Caucasian populations for several decades, with a doubling time of 10-14 years. An increase in incidence of about 5% per year has been reported in most Caucasian populations since the early 1960s. OBJECTIVES: This study was designed to determine the changing incidence of primary cutaneous malignant melanoma in Northern Ireland and to examine changes in survival rates from cutaneous malignant melanoma in two 5-year periods, 1984-88 and 1994-98. METHODS: One thousand three hundred and twenty-six patients with invasive primary cutaneous melanoma were included in the study. RESULTS: The age standardized rate of melanoma rose from 4.3 per 100,000 population per year in men and 8.6 per 100,000 population per year in women to 7.7 and 11.8, respectively, per 100,000 population per year in the 1994-98 period. Overall, the absolute 5-year survival for the 1984-88 period was 71.0% [95% confidence interval (CI) 66.9-75.1%] and 77.4% (95% CI 73.4-81.4%) for the 1994-98 period. Women consistently showed better survival at all ages and within almost all categories of thickness of primary tumour. Younger patients of both sexes showed better survival rates. CONCLUSIONS: When survival rates between the 1984-88 and 1994-98 periods were compared using multivariate analysis, we found that patients diagnosed in the second period had a one-third lower risk of dying than those in the earlier period. Much of this reduction was explained by changes in the number of melanomas of thin Breslow depth and ulcerated melanomas.

Adult↗
PubMed2003

Predicting survival after treatment for fracture of the proximal femur and the effect of delays to surgery.

BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the prognosis after treatment for femoral neck fracture, to assess the impact of delay to surgery, and to devise a clinical prediction rule and score. METHODS: A prospective observational study was conducted in which 1780 patients treated surgically in two teaching hospitals between 1 November 1997 and 31 October 1999 were followed over 12 months. Logistic regression was used to distinguish the effects of predictor variables on survival. Using a probit transformation of the predicted posterior probabilities of death, a prognostic score was devised with scores constrained so that a nominal score of approximately 90 represented a 50:50 chance of survival over 12 months. RESULTS: Mortality was 30.1% in men and 19.5% in women. Increasing age, male gender, longer pre-operative delay, a higher American Society of Anesthesiology score, a lower Mental Test score, and a lower activities of daily living (Barthel) score were associated with increased risks of death. Of those waiting between 1 and 5 days for surgery, approximately 8 medium-risk and 17 high-risk patients (with prognostic scores of 90 and 120, respectively) would have to have their delay reduced to < 24 hours to yield one additional survivor. CONCLUSION: The application of prediction rules must be guided by ethical, social, and scientific concerns.

Activities of Daily Living↗
PubMed2001

New polymorphisms in the interleukin-10 gene--relationships to myocardial infarction.

BACKGROUND: Interleukin-10 (IL-10) is a cytokine with anti-inflammatory and B-cell-stimulating activity. IL-10 is expressed in human atherosclerotic plaques and recent studies have shown the involvement of IL-10 in the atherosclerotic process. Therefore, we hypothesized that polymorphisms in the IL-10 gene might be associated with a predisposition to coronary heart disease. MATERIALS AND METHODS: To identify new polymorphisms in the human IL-10 gene, the entire coding sequence and the 3' flanking sequence of the gene were screened by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCR) followed by sequencing. The polymorphisms identified, and three others which have been previously described in the promoter region of the IL-10 gene (G-1082A, C-819T, C-592A), were then investigated in the ECTIM Study, a large population-based case-control study of myocardial infarction. RESULTS: Four new polymorphisms were identified: one in exon 1 (G+78/ex1A), which predicts a Glycine to Arginine change at position 15 in the putative signal peptide of the protein, two in the intron 3 (C+19/in3T, T+953/in3C) and one in the 3' flanking region (C+117T). All the IL-10 polymorphisms were in complete or nearly complete pairwise linkage disequilibrium. No case-control difference was found in genotype or allele frequencies for any of the polymorphisms. CONCLUSIONS: Our results suggest that IL-10 polymorphisms are not associated with an increased risk of myocardial infarction.

Adult↗
PubMed2001

Association studies between haemochromatosis gene mutations and the risk of cardiovascular diseases.

BACKGROUND: Haemochromatosis is a common genetic disorder, inherited as an autosomal recessive trait that results in a progressive accumulation of iron in most tissues of the body. Positive association studies have been recently published between cardiovascular diseases and heterozygosity for the major mutation C282Y in the haemochromatosis gene HFE. METHODS: In the present work, we have determined the HFE genotypes for C282Y and H63D in subjects from two case-control studies: the ECTIM and GENIC studies, designed to identify genetic variants associated with myocardial and brain infarction, respectively. In addition, we tested whether HFE mutations were associated with the degree of arteriosclerosis assessed non-invasively by Doppler ultrasonography on the carotid and femoral arteries, in a group of apparently healthy individuals (the AXA Study). RESULTS: The prevalence of 282Y, and 63D allele carriers, did not differ between cases and controls in the ECTIM and in the GENIC studies, while 63D but not 282Y carriers were more numerous among subjects with atherosclerotic plaques in the AXA Study. CONCLUSIONS: These three studies do not provide consistent evidence supporting the hypothesis that HFE mutations are associated with an increased risk of cardiovascular disease and with the development of arteriosclerosis.

Adolescent↗
PubMed2001

Flexible sigmoidoscopy and the changing distribution of colorectal cancer: implications for screening.

BACKGROUND AND AIMS: There has been a significant proximal shift in the distribution of colorectal cancer (CRC) in Northern Ireland over recent decades. The aim of this study was to investigate the potential implications of this proximal shift in CRC distribution on the efficacy of flexible sigmoidoscopy (FS) as a screening tool. PATIENTS AND METHODS: The site distribution of 5153 CRCs was available from the Northern Ireland Colorectal Cancer Register for the period 1990-1997. Similar data on 1241 CRCs between 1976 and 1978 were available from a previous study. Data on the site reached by FS were obtained from a prospectively collected endoscopy database at one of Northern Ireland's main teaching hospitals for the period 1993-1998. RESULTS: There was a significant proximal shift in CRC distribution between the two periods (23.5% proximal to the splenic flexure between 1976 and 1978 v 36.7% between 1990 and 1997; p<0.001). The descending colon was visualised during 74.4% of FS examinations. By combining the observed extent of FS examination with CRC site distribution, it was calculated that FS could have visualised 68.8% of CRCs between 1976 and 1978 but only 56.0% between 1990 and 1997. Extrapolating these data to a Northern Ireland screening programme involving FS and faecal occult blood testing suggests that significantly more CRCs could have been detected between 1976 and 1978 than between 1990 and 1997 (51.7% v 48.2%, respectively; p=0.03). CONCLUSIONS: This study confirms the previously documented left to right shift in CRC distribution in Northern Ireland and demonstrates that if this shift continues, FS will become less successful as a screening tool than is currently predicted.

Colorectal Neoplasms↗
PubMed2001

Characterization of polymorphic structure of cathepsin G gene: role in cardiovascular and cerebrovascular diseases.

Cathepsin G (CTSG), a serine protease released from activated neutrophils, may cause platelet activation, leading to intravascular thrombosis, thus contributing to cardiovascular and cerebrovascular disease. Applying the candidate gene approach, we screened the 5'-flanking region and the entire coding region of the CTSG gene for genetic variation by using polymerase chain reaction/single-strand conformation polymorphism analysis from 96 patients at high risk for myocardial infarction (MI). We identified 4 polymorphisms in the 5'-flanking region (G-618C, G-315A, C-179T, and C-160T) and 1 polymorphism in the coding region (Asn125Ser) of the gene and genotyped the participants in the Etude Cas-Temoins sur l'Infarctus du Myocarde (ECTIM Study), a case-control study for MI, and in the Etude du Profil Génétique de l'Infarctus Cérébral (GENIC Study), a case-control study for brain infarction (BI), for all identified genetic variants. The potential in vitro functionality of the 4 variants in the 5'-flanking region was investigated with transient transfection analyses in U937 cells with different allelic promoter constructs by using a luciferase assay. Our in vitro analyses did not reveal any differences for the investigated allelic constructs with respect to promoter activity, and none of the polymorphisms in the 5'-flanking region was associated with the available phenotypes in either study. Allele and genotype distributions of all identified polymorphisms did not globally differ between cases and controls in the ECTIM Study. However, in patients from the ECTIM Study, the Ser125 allele was significantly associated with elevated plasma fibrinogen levels (P=0.006), but this effect was not seen in controls (case-control heterogeneity, P=0.04). There was a significant interaction between CTSG Asn125Ser and the beta-fibrinogen gene polymorphism G-455A on plasma fibrinogen levels (P=0.04). In the GENIC Study, the odds ratio for BI associated with CTSG Ser125 carrying was 1.82 (95% CI 1.16 to 2.84, P=0.008) in patients without a history of cardiovascular or cerebrovascular diseases. Our results indicate that the CTSG Ser125 allele is associated with plasma fibrinogen levels in MI patients from the ECTIM Study and with BI in the GENIC Study. Further studies should be carried out to define the underlying mechanisms.

Adult↗
PubMed2001

Potentially malignant oral lesions in northern Ireland: a 20-year population-based perspective of malignant transformation.

This retrospective laboratory-based study investigates the potential for malignant transformation of oral mucosal lesions in a population of 1.6 million. Over the 20-year period there were 745 patients diagnosed with primary intra-oral squamous cell carcinoma (OSCC), 165 patients with dysplasia and 1182 patients with 'non-dysplastic' lesions (epithelial hyperplasia, hyperkeratosis epithelial atrophy, lichen planus and lupus erythematosus). Malignant transformation occurred in 15% of dysplasias and in 1% of 'non-dysplastic' lesions at average intervals after diagnosis of 48 and 65 months respectively. Only 6% of patients with OSCC had a pre-invasive lesion biopsied. These data suggest that white lesions are only rarely the pre-invasive phase of OSCC. It is possible therefore that early changes are red, small or even microscopic with carcinoma developing without a clinically observable phase. More effective management strategies will require the development of tissue markers to enhance early detection.

Adult↗
PubMed2000

Do polymorphisms of apoB, LPL or apoE affect the hypocholesterolemic response to weight loss?

To assess whether there is a differential hypocholesterolemic response to weight loss for subjects carrying polymorphisms of the apolipoprotein B and other genes. A before and after comparison of lipid parameters following a calorie controlled diet for an intervention period of 12 weeks. A lipid clinic based in a large teaching hospital. The difference in slope coefficients relating the percentage change in lipid parameters to the change in body weight (adjusted for age, gender and initial body mass index (BMI)), for genotype subgroups defined by polymorphisms of the 5'VNTR apoB gene, two mutations of the LPL gene and ApoE. One hundred and forty six subjects completed the intervention diet. While, on average, the intervention was successful (mean weight loss 3.9%), there was no statistically significant difference in the slope coefficients relating lipid change to weight loss for most of the genotypes tested. The slope difference for long versus short 5'VNTR alleles of the apoB gene was 0.445 (-1.307, 2.198) for apolipoprotein B and -0. 104 (-1.486, 1.278) for total cholesterol. However, subjects carrying at least one varepsilon4 allele were significantly hypo-responsive to weight loss, difference in slope coefficients -1.087 (-2.09, -0.084) and -1.320 (-2.589, 0.051) for total cholesterol and apoB, respectively. Although, this study is one of the largest of its kind, it has not replicated the findings of other smaller studies. These findings do not provide support for the use of genotype-targeted dietary advice in routine practice.

Adult↗
PubMed2000

Infection with virulent strains of Helicobacter pylori is not associated with ischaemic heart disease: evidence from a population-based case-control study of myocardial infarction.

BACKGROUND: Although the majority of evidence does not support association between Helicobacter pylori infection and ischaemic heart disease, the nature of this relationship may differ when virulence of the infecting strains are examined. METHODS AND RESULTS: The prevalence of IgG antibody evidence of infection with CagA positive stains of H. pylori was investigated in stored plasma samples from 259 cases of myocardial infarction (aged 25-70 years, 74 males) and 259 population based controls from the same area in Northern Ireland. Two-hundred and seventy (52.1%) subjects were seropositive for anti-CagA IgG. CagA seropositivity was more common in cases than in controls: 56.4 vs 47.9%, odds ratio for seropositivity in cases (95% CI) 1.41 (1.00, 1.99). Substantial attenuation of this relationship occurred on adjustment for age, sex, number of siblings, smoking and measures of socio-economic status: odds ratio (95% CI) 1.16 (0.79, 1.70). A similar pattern was seen for seropositivity for all H. pylori strains. CONCLUSION: Infection with the more virulent strains of H. pylori, as with all strains, is not associated with myocardial infarction.

Adult↗
PubMed2000

Angiotensin II type-I receptor and ACE polymorphisms and risk of myocardial infarction in men and women.

BACKGROUND: Findings relating an association between an insertion/deletion polymorphism of the angiotensin converting enzyme (ACE) gene and myocardial infarction (MI) have been mixed. While other loci, such as the angiotensin II type-I receptor (AT1R), may modulate risk, few studies have adequately documented the risk in women. We aimed to study whether the findings in respect of ACE and AT1R in UK men were borne out in women. METHODS: Cases of MI (305 women, 391 men) in Belfast and Glasgow have been compared to controls (291 women, 356 men). These new samples augment the original men (200 cases, 181 controls) included from Belfast in the ECTIM study. RESULTS: Among men, the odds ratio for MI for ACE (DD vs. ID + II) was 1.03 (0.79, 1.34) and among women, 0.69 (0.47, 1.01). This heterogeneity between the risks in men and women was significant in Glasgow (P = 0.02). Among men and women the odds ratio for MI for AT1R (CC vs. AC + AA) was 1.02 (0.71, 1.47). There was a small gradient in risk, such that the odds ratio for DD genotype was 0.86 (0.63, 1.17) among subjects homozygous for the common AT1R allele (AA): 0.94 (0.67, 1.30) among heterozygotes and 1.21 (0.53, 2.77) among CC subjects; but this interaction was not statistically significant. CONCLUSIONS: Some of the contradictory findings concerning the ACE polymorphism and the risk of MI may be due to heterogeneity in the risk between men and women. The AT1R1196 polymorphism is not an independent risk factor for MI in either sex.

Adult↗
PubMed2000

Stewardship or clinical freedom? variations in dialysis decision making.

BACKGROUND: It is generally agreed that acceptance criteria for dialysis have varied and changed over time and that implicit rationing, to some extent forced on clinicians by limited capacity, has been widely practised. Our objective was to study the basis and extent of variation in dialysis decision making among nephrologists in one NHS region. DESIGN AND METHODS: In a clinical judgement analysis, linear regression models were employed to reflect the impact of clinical and non-clinical cues on nephrologists' decisions to offer dialysis to 60 'paper patients' under current capacity constraints and under an assumption of no capacity limit. A short questionnaire was also completed by eight nephrologists to elicit their expressed decision drivers, which were subsequently compared with those tacitly derived from the appraisal of the 60 clinical vignettes. RESULTS: Doctors showed substantial variation in their propensity to offer dialysis and in their perceptions of the benefits of dialysis. Even for the five patients where the discordance in propensity to offer dialysis was least, the range in perceived gain in life expectancy was from 24 to 264 months (mean 91 months). The decision models had relatively good explanatory power with an average r(2) of 0.67 (0.39-0.90) and 0.70 (0.47-0.95) for decisions made under current capacity constraints and under an assumption of no limit capacity respectively. Surprisingly, for most doctors, the patient's age had very little impact on dialysis decisions but the magnitude of the beta-coefficients for the patient's mental state (mean -30.7) was of a similar order of magnitude to the coefficient for the principal 'renal' drivers (e.g. the mean coefficient for uraemic symptomatology under current capacity constraints was 47.7). The influence of other non-renal factors on the doctor's likelihood to offer dialysis was largely independent of the capacity assumption. A comparison of the doctor's stated decision drivers with those tacitly derived from their decision models showed only modest correlation. CONCLUSIONS: The extent to which doctors vary in their propensity to offer dialysis is substantial. Very few non-clinical cues appear to influence the decision to offer dialysis. The most important non-renal factor in determining dialysis decisions was the patient's mental state.

Decision Making↗