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Biomedical subjects

Chris Patterson

Publications and source records attributed to Chris Patterson.

At least 19 recordsLinked to original sources
PubMed2006

The neuropeptide genes TAC1, TAC3, TAC4, VIP and PACAP(ADCYAP1), and susceptibility to multiple sclerosis.

The related immunomodulatory neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylyl cyclase activating peptide (PACAP; gene symbol ADCYAP1) have recently been proposed as novel therapeutics for the treatment of multiple sclerosis (MS). These neuropeptides, as well as those belonging to the tachykinin family exert pleiotropic effects, many of which are of relevance to central nervous system inflammation. In the present study, we have analysed 14 single nucleotide polymorphisms (SNPs) and 4 microsatellite markers in the VIP, ADCYAP1, TAC3 and TAC4 genes for susceptibility to MS in a case-control collection from Northern Ireland. Following correction for multiple comparisons, we did not find any significant associations between single polymorphic markers or multiple-marker haplotypes and susceptibility to MS. Furthermore, we analysed 2 SNPs in the TAC1 gene in a set of Sardinian trio MS families, based on our previous observation of association of these SNPs with MS in the Northern Irish (Genes Immun. 2005, 6, 265-270). Analysis of these SNPs in the Sardinians was not significant though a similar trend to that originally observed in the Northern Irish was present. Meta-analysis of the Sardinian and Northern Irish TAC1 SNP genotype data revealed a Mantel-Haenszel Common OR Estimate for the TAC1 intron 1 SNP rs2072100 of 0.76 (95% CI 0.63-0.92; P=0.005; A allele) and for the TAC1 promoter SNP rs7793277 of 0.76 (95% CI 0.615-0.95; P=0.014; C allele). Our data advocate a need for further exploration of the TAC1 gene region in MS.

Disease Susceptibility↗
PubMed2006

Learning from death: a hospital mortality reduction programme.

PROBLEM: There are wide variations in hospital mortality. Much of this variation remains unexplained and may reflect quality of care. SETTING: A large acute hospital in an urban district in the North of England. DESIGN: Before and after evaluation of a hospital mortality reduction programme. STRATEGIES FOR CHANGE: Audit of hospital deaths to inform an evidence-based approach to identify processes of care to target for the hospital strategy. Establishment of a hospital mortality reduction group with senior leadership and support to ensure the alignment of the hospital departments to achieve a common goal. Robust measurement and regular feedback of hospital deaths using statistical process control charts and summaries of death certificates and routine hospital data. Whole system working across a health community to provide appropriate end of life care. Training and awareness in processes of high quality care such as clinical observation, medication safety and infection control. EFFECTS: Hospital standardized mortality ratios fell significantly in the 3 years following the start of the programme from 94.6 (95% confidence interval 89.4, 99.9) in 2001 to 77.5 (95% CI 73.1, 82.1) in 2005. This translates as 905 fewer hospital deaths than expected during the period 2002-2005. LESSONS LEARNT: Improving the safety of hospital care and reducing hospital deaths provides a clear and well supported goal from clinicians, managers and patients. Good leadership, good information, a quality improvement strategy based on good local evidence and a community-wide approach may be effective in improving the quality of processes of care sufficiently to reduce hospital mortality.

England↗
PubMed2006

Might how you look influence how well you are looked after? A study which demonstrates that GPs perceive socio-economic gradients in attractiveness.

OBJECTIVE: To test the hypothesis that more disadvantaged patients are perceived by general practitioners (GPs) as being less attractive than their more affluent peers. DESIGN: Three hundred and twenty five consecutive ambulant patients attending 15 GPs' surgeries in Northern Ireland, UK, had three digital photographs taken; two of their face (smiling and non-smiling) and one of their face and upper trunk. Photographs were assessed by 30 GPs from practices other than those used to select the patients. Patients were subdivided into 'more affluent', 'average' and 'more deprived' groups based on their household tenure, level of educational attainment and car availability. The age and sex of the GP-assessors was recorded along with the average deprivation score for their own practice population. The relationship between patient, GP and practice characteristics was explored using multilevel modelling to take account of the hierarchical nature of the dataset. The main outcome measure was the perceived attractiveness score of the patient as rated by the GP. RESULTS: Of those invited, 301 (92%) participated in the study. The mean age of patients was 49.6 (standard deviation 6.1) years and 59% were female. GPs rated younger patients more attractive than older patients; each additional 10 years reduced the attractiveness scores by an average of 2.7 points (95% confidence intervals 1.4-3.9, P < 0.001). Patients from higher socio-economic backgrounds were assessed as more attractive than their less affluent peers, the mean difference being 7.8 points (5.8-9.9, P < 0.001). The difference in attractiveness scores between affluent and deprived patients was greatest when the GP assessor came from a practice serving predominantly deprived patients. CONCLUSION: The perceived difference in the average attractiveness scores between affluent and deprived patients is large and, though this study does not prove it, there is sufficient circumstantial evidence to indicate that it might play a significant role in modifying the medical encounter.

Female↗
PubMed2005

Which hemostatic markers add to the predictive value of conventional risk factors for coronary heart disease and ischemic stroke? The Caerphilly Study.

BACKGROUND: Few studies have examined whether hemostatic markers contribute to risk of coronary disease and ischemic stroke independently of conventional risk factors. This study examines 11 hemostatic markers that reflect different aspects of the coagulation process to determine which have prognostic value after accounting for conventional risk factors. METHODS AND RESULTS: A total of 2398 men aged 49 to 65 years were examined in 1984 to 1988, and the majority gave a fasting blood sample for assay of lipids and hemostatic markers. Men were followed up for a median of 13 years, and cardiovascular disease (CVD) events were recorded. There were 486 CVD events in total, 353 with prospective coronary disease and 133 with prospective ischemic stroke. On univariable analysis, fibrinogen, low activated protein C ratio, D-dimer, tissue plasminogen activator (tPA), and plasminogen activator inhibitor-1 (PAI-1) were associated significantly with risk of CVD. On multivariable analyses with conventional risk factors forced into the proportional hazards model, fibrinogen, D-dimer, and PAI-1 were significantly associated with risk of CVD, whereas factor VIIc showed an inverse association (P=0.001). In a model that contained the conventional risk factors, the hazard ratio for subsequent CVD in the top third of the distribution of predicted risk relative to the bottom third was 2.7 for subjects without preexisting CVD. This ratio increased to 3.7 for the model that also contained the 4 hemostatic factors. CONCLUSIONS: Fibrinogen, D-dimer, PAI-1 activity, and factor VIIc each has potential to increase the prediction of coronary disease/ischemic stroke in middle-aged men, in addition to conventional risk factors.

Aged↗
PubMed2005

Cardiovascular responses and endurance during isometric exercise in patients with Type 2 diabetes compared to control subjects.

BACKGROUND: While it is well documented that diabetes impairs the microcirculation, its effect on isometric exercise has not been determined. MATERIAL/METHODS: Isometric strength and endurance of the handgrip muscles for a series of 2 fatiguing isometric contractions at a tension of 40% of the maximum strength were assessed in 10 subjects with Type 2 diabetes compared to 10 control subjects; 5 minutes were allowed between the contractions. Blood pressure (BP), heart rate (HR), blood flow (BF) of the whole arm and of the skin on the chest and foot were measured. RESULTS: Strength and endurance for the first contraction was the same in control subjects compared to subjects with Type 2 diabetes (p>0.05), but endurance of the second contraction was significantly less in subjects with diabetes (p<0.01). HR increased significantly (p<0.01) by over three fold during exercise in control subjects compared to subjects with diabetes. Resting and peak blood pressures were greater in subjects with type 2 diabetes compared to control subjects (p<0.01). Forearm blood flow was significantly lower at rest, during exercise and post exercise in subjects with diabetes compared to control subjects (p<0.01). CONCLUSIONS: The results are probably explained by the damage to the microcirculation seen in subjects with diabetes.

Adult↗
PubMed2005

SNPs at the APOA5 gene account for the strong association with hypertriglyceridaemia at the APOA5/A4/C3/A1 locus on chromosome 11q23 in the Northern Irish population.

Serum triglyceride levels (TG) are important independent risk factors for coronary heart disease. The apolipoproteins C-III (apoCIII) and A-V (apoAV) are central to normal TG metabolism and the complete sequence analysis of these genes was carried out in severe cases (TG > 9 mmol/l) and controls (TG < 2 mmol/l). A total of 53 SNPs were identified in these genes with 17 being novel to this study. Further analysis defined four APOC3 SNPs and three APOA5 SNPs showing strong association with TG levels. Analysis of the two major SNPs from APOA5 [c.56C > G, c.-3A > G] and from APOC3 [c.102C > T, c.340C > G] using THESIAS has identified two major haplotypes relative to the most common CACC haplotype showing very strong association with hypertriglyceridaemia, CGTG and GATC (odds ratio 7.45 and 5.26). Logistic regression analysis of these four SNPs revealed that, carriage of the APOA5 c.56 G allele (odd ratios 4.49) and the APOA5 c.-3 G allele (odds ratio 3.23) were strong independent predictors of hypertriglyceridaemia (P < 0.001), whereas in contrast, carriage of the APOC3 c102 T allele (odds ratio 1.35) and the APOC3 c.340 G allele (odds ratio 1.37), did not show any significant effects that were independent of APOA5.

Apolipoprotein A-I↗
PubMed2005

Family-based association studies of lipid gene polymorphisms in coronary artery disease.

Dysfunction of lipid-metabolizing proteins is implicated in the pathogenesis of coronary artery disease. Single nucleotide polymorphisms in genes that encode sterol regulatory binding protein-1a, adenosine triphosphate binding cassette-A1, hepatic lipase, lipoprotein lipase, and cholesteryl ester transfer protein were assessed as potential markers of disease susceptibility in a family-based study of 1,012 patients from 386 families. Association between single nucleotide polymorphisms and coronary artery disease was tested by the combined transmission disequilibrium test/sib transmission disequilibrium test and pedigree disequilibrium test. After Bonferroni's correction, the pedigree disequilibrium test demonstrated significant excess transmission (p <0.0083) to affected patients of the hepatic lipase -514 T allele, which suggests that this may constitute a novel disease-susceptibility locus.

Adult↗
PubMed2005

Prevalence of obstructive lung disease in a general population sample: the NICECOPD study.

BACKGROUND: There are little data available on the prevalence of chronic obstructive pulmonary disease (COPD) in the United Kingdom. The Northern Ireland Cost and Epidemiology of Chronic Obstructive Pulmonary Disease (NICECOPD) study is a two-stage survey to examine the prevalence of obstructive lung disease in a general population sample in the Greater Belfast area. METHODS: In stage one 4000 subjects aged 40-69 years were selected at random from the general population. They were posted a short screening questionnaire concerning respiratory symptoms. Respondents were divided into 'symptomatic' and 'asymptomatic' groups according to their responses. In stage two, a sample of symptomatic and asymptomatic subjects completed a more intensive assessment that included a detailed questionnaire on medical history, spirometry, skin allergy testing and serial peak flow measurements. Spirometric criteria for airflow obstruction were FEV1/FVC ratio of <70% with FEV1 < 80% predicted. Subjects were assigned diagnoses according to a pre-arranged protocol. RESULTS: The survey was conducted from May 1999 to May 2001. There was a 67% response rate to the stage 1 screening questionnaire and 1330 responders were identified as being eligible to take part in stage 2. In total, 722 subjects completed a detailed assessment (50.8% Male, symptomatic, n = 326; asymptomatic, n = 396). COPD was diagnosed in 12.3% (8.8, 15.8) of the symptomatic and 2.2% (0.8, 3.6) of the asymptomatic group. The estimated prevalence of obstructive lung disease in the total population age 40-69 years was 14.4%: 6.3% COPD; 7.2% asthma; 0.9% with indeterminate airflow obstruction. In men, the prevalence of COPD varied from 4.9% in those aged 40-49 years to 12.3% in those aged 60-69 years and in women, varied from 1.4% in 40-49 years of age to 4.5% in 60-69 years. CONCLUSION: The data suggest that COPD and asthma are common conditions in the general population and should inform future plans to address the burden of disease.

Adult↗
PubMed2005

Pharmacogenomics of responsiveness to interferon IFN-beta treatment in multiple sclerosis: a genetic screen of 100 type I interferon-inducible genes.

OBJECTIVES: Interferon IFN-beta is indicated for the treatment of multiple sclerosis. A significant proportion of patients show a poor clinical response to therapy. Type I interferon exerts its effect at least partially through interaction of specific transcription factors with interferon-stimulated response elements (ISREs), mostly located in promoter regions of its target genes. We hypothesized that polymorphisms may occur within or close to ISRE elements, altering type I interferon inducibility and ultimately leading to a modified clinical response in carriers. METHODS: We selected 100 ISRE-containing genes and sequenced their promoter regions in small genomic deoxyribonucleic acid pools of responding and nonresponding patients, as well as healthy control subjects. A selection of polymorphisms discovered by this approach was scrutinized subsequently in a collection of individual deoxyribonucleic acid samples. RESULTS: We identified 4 genes containing polymorphisms associated with response to recombinant IFN-beta: IFNAR1 (P = .036), LMP7 (P = .002; odds ratio [OR], 6.37 [95% confidence interval (CI), 1.84-24.1]), CTSS (P = .02; OR, 0.38 [95% CI, 0.18-0.84]), and MxA (P = .015; OR, 3.37 [95% CI, 1.11-11.4]). Logistic regression analysis with treatment outcome used as the dependent variable and genotype as the independent variable revealed 2 genes, LMP7 (OR, 0.55 [95% CI, 0.34-0.89]) and MxA (OR, 0.41 [95% CI, 0.19-0.88]), that were independently associated with treatment response. CONCLUSIONS: Our work confirms and extends previous indications for a polygenic mechanism involved in bringing about responsiveness to recombinant IFN-beta. The identification of 2 genes active in the antigen processing and presentation cascade; that is, LMP7, coding for the proteasome subunit beta, and CTSS, coding for cathepsin S; as potential response modifiers may identify this pathway as being of particular relevance to phenotypic expression of response heterogeneity.

Chromosome Mapping↗
PubMed2005

Comparison of individual and pooled sampling methods for detecting bacterial pathogens of fish.

Examination of finfish populations for viral and bacterial pathogens is an important component of fish disease control programs worldwide. Two methods are commonly used for collecting tissue samples for bacteriological culture, the currently accepted standards for detection of bacterial fish pathogens. The method specified in the Office International des Epizooties Manual of Diagnostic Tests for Aquatic Animals permits combining renal and splenic tissues from as many as 5 fish into pooled samples. The American Fisheries Society (AFS) Blue Book/US Fish and Wildlife Service (USFWS) Inspection Manual specifies the use of a bacteriological loop for collecting samples from the kidney of individual fish. An alternative would be to more fully utilize the pooled samples taken for virology. If implemented, this approach would provide substantial savings in labor and materials. To compare the relative performance of the AFS/USFWS method and this alternative approach, cultures of Yersinia ruckeri were used to establish low-level infections in groups of rainbow trout (Oncorhynchus mykiss) that were sampled by both methods. Yersinia ruckeri was cultured from 22 of 37 groups by at least 1 method. The loop method yielded 18 positive groups, with 1 group positive in the loop samples but negative in the pooled samples. The pooled samples produced 21 positive groups, with 4 groups positive in the pooled samples but negative in the loop samples. There was statistically significant agreement (Spearman coefficient 0.80, P < 0.001) in the relative ability of the 2 sampling methods to permit detection of low-level bacterial infections of rainbow trout.

Animals↗
PubMed2005

Sweat production during global heating and during isometric exercise in people with diabetes.

BACKGROUND: While sweat production in response to heat is impaired in people with diabetes, sweat production has not been examined during isometric exercise. MATERIAL/METHODS: Eight subjects with type 2 diabetes and 9 control subjects exerted a fatiguing isometric contraction of the handgrip muscles at a tension of 40% of the maximum voluntary strength (MVC) after exposure to a 32 deg C environment for 30 min. compared to 10 controls and 10 subjects with diabetes exposed to a 39 deg C environment. RESULTS: Sweat was impaired to all areas of the body during heat exposure in patients with diabetes under both environmental conditions. For example, on the chest, the average sweat rates after exposure to the 32 deg environment was 259.2 +/- 55.2 nanoliters/min in control subjects and 198.3 +/- 46.2 nanoliters/min for subjects with diabetes. Compared to the 32 deg C environment, control subjects increased sweat in all 4 areas proportionally more than subjects with diabetes. Sudomotor rhythm was present in sweat in control subjects at a rate of repetition of 11 and 50 seconds but almost absent in subjects with diabetes. During exercise, sweat rates slowly increased from the beginning to the end of the exercise. But the head of the subjects with diabetes showed hypersweating while the other areas showed diminished sweating compared to control subjects. CONCLUSIONS: Thus some of the impairment in sweating may be due to central mechanisms associated with heat sensitivity or in the hypothalamus and not to the sweat glands themselves.

Adult↗
PubMed2004

Paraoxonase polymorphisms PON1 192 and 55 and longevity in Italian centenarians and Irish nonagenarians. A pooled analysis.

BACKGROUND: PON1, an arylesterase, associated with high density lipoprotein (HDL), protects low density lipoprotein (LDL) against oxidative modification. Common polymorphisms PON1 55 (L/M) and 192 (Q/R) in the PON1 gene associate with atherosclerosis and heart disease. Because long-lived people seem protected from premature vascular death, we conducted a pooled statistical analysis to assess any association between these polymorphisms and longevity in a large combined group of Italian centenarians and octo/nonagenarians from Northern Ireland (NI). MATERIALS AND METHODS: Separated DNA was available from 1479 subjects from Italy and Northern Ireland (NI). In Italy 308 centenarians (males 67, females 241, mean age 100.8, SD2.1 years) and 579 young controls (males 347, females 232, mean age 40.7, SD 12.7 years) were included in the study. In NI, 296 octo/nonagenarians (males 92, females 204, mean age 89.8, SD 5.7 years) and 296 young sex-matched subjects (mean age 13.0, SD 1.4 years) had available DNA. PON1 55 (L/M) and 192 (Q/R) polymorphisms were studied using a PCR-RFLP approach. RESULTS: There was a significant difference in PON1 192 genotypes in Italian centenarians compared to younger controls (X(2)= 6.8, df = 2 p= 0.03) and a similar but non significant trend between octo/nonagenarian and young subjects in NI (X(2) = 4.0, df=2, p=0.14). Using logistic regression analysis on the combined Italian and Irish datasets, there was a small survival advantage for centenarian and octo/nonagenarian subjects who were heterozygous for PON1 192 R allele, (OR 1.3, CI 1-1.6; p=0.04 with a stepwise increase for RR homozygous subjects (OR 1.7, CI 1.1-2.6; p = 0.02) compared to QQ subjects. Comparing R and Q alleles there was a survival advantage for octo/nonagenarian/centenarian subjects who carried the R allele (OR 1.3, CI 1.1-1.5; p = 0.007) but there was no sex-specific effect p =0.77) LL, LM and MM genotypes of PON 55 polymorphisms showed similar frequencies in Italy (39.9, 47.0, 13.1%) and Ireland (39.5, 48.6, 11.9%) with no age or sex-related differences. The PON1 192R/Q and PON55L/M loci were in strong linkage disequilibrium with a Lewontin's D' coefficient -0.928 (elderly) and -0.965 (young). There was a significant difference in haplotype frequency of these linked loci in older compared to younger subjects (Likelihood Ratio X(2) = 9.60, df = 3, p= 0.02). CONCLUSION: These data suggest a modest association between the 192R allele and longevity in two very elderly populations in two European countries. Being homozygous for 192 RR further enhances survival advantage but this effect was not found to be sex specific. This finding is of interest because the 192R allele has previously been associated with increased risk of coronary heart disease. On the other hand, the 192R allele shows higher enzymatic activity, using paraoxon as substrate, and we postulate that its role in the metabolism of potentially toxic chemicals or other metabolic pathways may be important in survival to very old age.

Adult↗
PubMed2003

HLA haplotypes and TNF polymorphism do not associate with longevity in the Irish.

Polymorphism of the human leukocyte antigen has been implicated in a number of autoimmune disorders including ageing. In the course of the present study, no association of the human leukocyte antigen (HLA)-A1, B8, DR3 haplotype with a male Irish aged population, as previously reported, was observed. Two polymorphic nucleotides in the TNF cluster (G-308A TNF-alpha and G+252A TNF-beta), associated with increased TNF-alpha production, were shown to be in tight linkage disequilibrium with the class I and II HLA loci, generating HLA haplotypes with extended linkage disequilibrium. However, no age-related allele or genotype frequencies were observed for either polymorphic nucleotide.

Adult↗
PubMed2003

Family history, longevity, and risk of coronary heart disease: the PRIME Study.

BACKGROUND: To assess the contribution of family history of coronary heart disease (CHD) and longevity in parents to 5-year incidence of coronary events in middle-aged men. METHODS: A prospective study in men from Northern Ireland and the French cities and environs of Lille, Strasbourg, and Toulouse. A total of 10 600 men aged 50-59 years were examined between 1991 and 1994 and followed annually by questionnaire for incident cases of coronary disease. A detailed family history was taken and a quantitative family risk score for CHD was calculated for each subject. Five-year follow-up is complete; all coronary events (coronary deaths, myocardial infarction, and angina) documented by clinical records were reviewed by an independent medical committee. RESULTS: At screening, 9758 subjects were free of clinical and historical evidence of CHD; in this group there were 317 coronary events by 5 years of follow-up. Subjects whose parents had both survived until >/=80 years showed a relative odds of 0.49 (95% CI: 0.31-0.77) for risk of a coronary event compared with subjects whose parents had not survived until >/=80 years old with adjustment for age and nine other risk factors including family history. The pattern of results was similar in France and Northern Ireland, although parental survival was longer in France. Likewise, subjects with a strong family history showed a relative odds of 1.93 (95% CI: 1.25-3.00) compared with subjects without such a history, after adjustment for age and the nine risk factors including parental longevity. The pattern of results was similar in France and Northern Ireland. CONCLUSIONS: These results indicate that a family history of coronary disease and parental longevity, although related, act independently of one another and of other major cardiovascular risk factors in predicting 5-year risk of subsequent coronary events.

Aged↗
PubMed2002

Molecular diversity of the HLA-C gene identified in a caucasian population.

A DNA typing procedure, based on a two stage polymerase chain reaction-sequence-specific oligonucleotide probe (PCR-SSOP) typing strategy, has been developed and applied to DNA from 1000 healthy individuals from the Northern Ireland region. The two-stage procedure involves human leukocyte antigen (HLA-C) identification through the use of a medium resolution PCR-SSOP system, followed by four secondary group specific PCR-SSOP systems, to enable allele resolution. The PCR-SSOP systems were designed for the identification of HLA-Cw alleles with possible discrimination within exons 2 and 3 of the HLA-C gene, i.e., HLA-Cw*01-Cw*16. PCR-SSP tests were designed for the resolution of HLA-Cw*17 and -Cw*18 alleles. The systems can also be used independently of each other if selective allele resolution is required. HLA-Cw allele frequencies occurring within the Northern Ireland population have been compiled, along with estimations of HLA-B/Cw haplotype frequencies.

Genetic Variation↗
PubMed2002

Frequency of cytokine polymorphisms in populations from western Europe, Africa, Asia, the Middle East and South America.

PCR-SSOP identification procedures for IL-2, IL-6, IL-10, TNF-alpha and TNF-beta cytokine polymorphisms have been developed. Application of the procedures to a range of diverse geographically distributed populations has identified ethnic differences within the groups studied. Five populations were investigated, Northern Ireland, South African Zulu, Omani, Singapore Chinese and Mexican Mestizos.

Africa↗