Biomedical subjects

J H Barrett

Publications and source records attributed to J H Barrett.

At least 37 records · Page 2Linked to original sources

PubMed2001

Women with inflammatory polyarthritis have babies of lower birth weight.

OBJECTIVE: To assess the effect on fetal outcome, and development of the child over the first 8 months of life, of rheumatoid arthritis (RA) during pregnancy. METHODS: Women with RA or undifferentiated inflammatory polyarthritis (IP) were recruited from throughout the UK and followed prospectively from late pregnancy to 8 months postpartum. Matched controls were obtained from general practitioners. The babies' health at birth and development at 8 months were monitored by the weight, head circumference, and length. Potential confounding variables were noted. RESULTS: One hundred thirty-three women with RA or undifferentiated IP took part in the study. There were 5 (4%) admissions for hypertension during pregnancy and no cases of preeclampsia. Cesarean section was common (23%). Matched controls were found for 103 (77%) subjects. There were no significant differences between groups in head circumference or length at birth. Babies born to women with arthritis had lower mean birth weight than controls [3.3 kg (standard deviation 0.5) compared to 3.5 kg (0.4); p = 0.004], even after adjustment for potential confounding factors. Within the patient group those whose arthritis was in remission had significantly heavier babies than those with active disease [mean 3.5 kg (0.5) compared with 3.3 kg (0.5); p = 0.04]. This trend was still apparent at 8 months, but differences were no longer statistically significant. CONCLUSION: This is the first relatively large prospective study of the effects on mother and baby of RA during pregnancy. The results suggest that, although disease improves in most women during pregnancy, it is still sufficiently active to have a modest negative effect on birth weight.

Age Factors↗

PubMed2000

Breast-feeding and postpartum relapse in women with rheumatoid and inflammatory arthritis.

OBJECTIVE: To test the hypothesis that breast-feeding increases the risk of postpartum flare in inflammatory polyarthritis. METHODS: We compared disease activity during pregnancy and at 6 months postpartum among 49 non-breast-feeders, 38 first-time breast-feeders, and 50 repeat breast-feeders. RESULTS: After we adjusted for possible confounders, including treatment, first-time breast-feeders had increased disease activity 6 months postpartum, based on self-reported symptoms, joint counts, and C-reactive protein levels. CONCLUSION: Postpartum flare may be induced by breast-feeding.

Adult↗

PubMed2000

Subtyping of juvenile idiopathic arthritis using latent class analysis. British Paediatric Rheumatology Group.

OBJECTIVE: To use statistical techniques to identify underlying subtypes of juvenile idiopathic arthritis (JIA) that best explain the observed relationships of clinical and laboratory variables, and to compare the statistically derived subtypes with those defined by the International League of Associations for Rheumatology (ILAR) criteria and examine them for HLA associations. METHODS: Information on 572 patients diagnosed as having JIA was summarized by 10 clinical and laboratory categorical variables (age at onset, large joint involvement, small joint involvement, polyarthritis, symmetric arthritis, spinal pain, fever, psoriasis, antinuclear antibodies [ANA], and rheumatoid factor). Latent class analysis (LCA) was used to identify underlying ("latent") classes that explained the relationships among the observed variables. Statistical models incorporating 5-8 latent classes were applied to the data. RESULTS: The 7-class model was the most appropriate. Patterns of joint involvement and the presence of ANA were influential in determining latent classes. There was some correspondence between the latent classes and the ILAR categories, but they did not coincide completely. Significant differences between the latent classes were seen for 3 HLA haplotypes (DRB1*04-DQA1*03-DQB1*03, DRB1*13-DQA1*01-DQB1*06, and DRB1*08-DQA1*0401-DQB1*0402). CONCLUSION: LCA provides a novel approach to the task of identifying homogeneous subtypes within the umbrella of JIA. In further work, the identified latent classes will be examined for associations with other candidate genes and for differences in outcome.

Adolescent↗

PubMed2000

A two-stage, genome-wide screen for susceptibility loci in primary Raynaud's phenomenon.

OBJECTIVE: To identify chromosomal regions containing genes involved in the susceptibility to primary Raynaud's phenomenon (RP). METHODS: Six extended families with multiple individuals affected with primary RP (n = 37) were examined for linkage in a 2-stage, whole-genome screen, using a total of 298 microsatellite markers. RESULTS: Multipoint, nonparametric linkage analysis identified 5 areas of possible linkage, with a nominal level of significance of P < or = 0.05. Analysis of a finer map of markers in these regions defined the regions of linkage as 21.4 cM on 6q13-6q23.3 (D6S261; P = 0.0004), 10.2 cM on 7p22-7p15 (D7S664; P = 0.014), 1.6 cM on 9p23-9p22 (D9S156; P = 0.0075), 5.1 cM on 17p13.1-17p12 (D17S1791; P = 0.036), and 11.8 cM on Xp11.4-Xp11.23 (DXS8054; P = 0.006). Three potential candidate genes map to these regions: the beta subunit of the muscle acetylcholine receptor and the serotonin 1B and 1E receptors. CONCLUSION: These results provide evidence of the presence and location of genes that are involved in the genetic susceptibility to primary RP.

Adolescent↗

PubMed2000

Linkage of rheumatoid arthritis to insulin-dependent diabetes mellitus loci: evidence supporting a hypothesis for the existence of common autoimmune susceptibility loci.

OBJECTIVE: To seek potential autoimmune disease susceptibility loci by testing for linkage and linkage disequilibrium between insulin-dependent diabetes mellitus (IDDM) susceptibility loci and rheumatoid arthritis (RA). METHODS: Five IDDM susceptibility loci map to 2 chromosomal regions, chromosome 2q31-34 (IDDM7, 12, and 13) and chromosome 6q25-27 (IDDM5 and 8). Microsatellite markers within these regions were genotyped in 255 RA families, by fluorescence-based genotyping technology. Evidence for linkage disequilibrium was assessed using the extended transmission disequilibrium test (ETDT) program. RESULTS: With the ETDT, we found evidence for linkage disequilibrium of the marker D6S446, at IDDM8, with RA (P < 0.0001). There was additional evidence for linkage disequilibrium with 2 markers at IDDMS (D6S311 and D6S440) (P = 0.016 and P = 0.017, respectively). There was no evidence for significant linkage disequilibrium of RA with any markers at IDDM7, 12, or 13. CONCLUSION: These results support the hypothesis that there are autoimmune disease genes at IDDM5 and IDDM8.

Alleles↗

PubMed2000

Seven unique food consumption patterns identified among women in the UK Women's Cohort Study.

OBJECTIVE: [corrected] To identify groups of subjects with similar food consumption patterns so that complex disease-diet relationships can be investigated at the level of the whole diet, rather than just in terms of nutrient intake. SUBJECTS: 33,971 women in the UK Women's Cohort Study. 60,000 women on the World Cancer Research Fund mailing list were initially invited to take part. Subjects were selected to include a high proportion of vegetarians. DESIGN: The cohort completed a 217 item food frequency questionnaire. Cluster analysis was used to identify groups of women with similar food consumption patterns. Clusters were compared on socio-demographic characteristics, indicators of health and diet, and nutrient intakes. RESULTS: Seven clusters were identified including two vegetarian clusters. Groups appeared to be differentiated by differences in food types and in diversity of diet. Socio-demographic, health and diet characteristics and nutrient intakes all differed significantly between groups. CONCLUSION: Classifying diets in more pragmatic terms than just nutrient intake should provide valuable insight into understanding complex diet-disease relationships. Dietary advice, whilst based on nutrient content of meals, needs to take account of the combinations of different food types that people naturally choose to use together. SPONSORSHIP: World Cancer Research Fund.

Adult↗

PubMed2000

A family-based and case-control association study of the dopamine D4 receptor gene and dopamine transporter gene in attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is a highly heritable psychiatric condition of early childhood onset characterised by marked inattention, hyperactivity and impulsiveness. Molecular genetic investigations of ADHD have found positive associations with the 480-bp allele of a VNTR situated in the 3' untranslated region of DAT1 and allele 7 of a VNTR in exon 3 of DRD4. A number of independent studies have attempted to replicate these findings but the results have been inconsistent. We used both family-based and case control approaches to examine these polymorphisms in a sample of 137 children diagnosed with ICD-10, DSM-IV or DSM-III-R ADHD. We found no evidence of association with the DAT1 polymorphism, despite a sample size that has up to 80% power to detect a previously reported effect size. We observed a significant increase in the DRD4 7 repeat allele amongst ADHD probands (21.7%) and their parents (18.9% in mothers, 22.3% in fathers), compared to ethnically matched controls (12.8%). However TDT analysis showed no preferential transmission of allele 7 to ADHD probands.

Adult↗

PubMed2000

Association of markers for TGFbeta3, TGFbeta2 and TIMP1 with systemic sclerosis.

OBJECTIVES: To investigate whether six microsatellite markers known to map closely to genes involved in fibrosis are associated with systemic sclerosis (SSc). METHODS: Markers mapping to TGFbeta1, TGFbeta2, TGFbeta3, PDGFB, TIMP1 and COL5A2 were genotyped and allele frequency distributions compared in 191 patients and 196 controls. As TIMP1 maps to the X chromosome, male and females were analysed separately. Markers associated with SSc were further investigated according to whether patients had limited (lcSSc) or diffuse (dcSSc) cutaneous fibrosis. RESULTS: Associations were found between SSc and markers for TGFbeta3 (chi(2)=17.3, df=8, P=0.02), TGFbeta2 (chi(2)=25.2, df=13, P=0.02) and TIMP1 (with male SSc, chi(2)=11.9, df=5, P=0.03), between lcSSc and the TGFss2 marker (chi(2)=25.6, df=13, P=0.02), and between dcSSc and TGFbeta3 marker (chi(2)=27.1, df=8, P=0.001). Between lcSSc and dcSSc patients, the allele frequency distribution differed only for the TGFbeta3 marker (chi(2)=16.5, df=6, P=0.01). CONCLUSION: These associations indicate a possible role for TGFbeta3, TGFbeta2 and TIMP1 in genetic susceptibility to SSc and for TGFbeta3 in determining the degree of cutaneous fibrosis.

Adult↗

PubMed1999

Does rheumatoid arthritis remit during pregnancy and relapse postpartum? Results from a nationwide study in the United Kingdom performed prospectively from late pregnancy.

OBJECTIVE: To ascertain the influence of pregnancy on disease activity in women with rheumatoid arthritis (RA) during pregnancy and postpartum. METHODS: One hundred forty pregnant women were recruited from a nationwide campaign and were followed prospectively in the last trimester and at 1 and 6 months postpartum. Standardized assessment of joint symptoms, examination of inflamed joints, and the Health Assessment Questionnaire (HAQ) were the main measures of disease activity. RESULTS: There was only a modest fall in HAQ scores during pregnancy, with >25% of women having substantial levels of disability. Other parameters of disease activity showed a greater trend toward improvement, although only 23 (16%) were in complete remission (no joints with active disease and no therapy). Similarly, there was relatively little change in the distribution of HAQ scores from pregnancy to postpartum. There was, however, a statistically significant increase in the mean number of inflamed joints compared with the findings during pregnancy. Analysis of the possible influence of treatment suggested that therapy was associated with more severe disease and was not related to reduction in disease activity. CONCLUSION: This, the largest prospective study of the influence of pregnancy on RA activity, has demonstrated widespread variability in disease response.

Adult↗

PubMed1999

Estimating the incidence of rheumatoid arthritis: trying to hit a moving target?

OBJECTIVE: To examine the effect of delay between symptom onset and notification to an arthritis register and the effect of application of the American College of Rheumatology (ACR; formerly, the American Rheumatism Association) 1987 criteria in a cumulative manner on estimates of the incidence of rheumatoid arthritis (RA). METHODS: General practitioners and/or hospital consultants in the Norwich Health Authority, Norfolk, UK, notified the Norfolk Arthritis Register (NOAR) of all patients who had onset of inflammatory polyarthritis (swelling of > or =2 joints) during 1990. The patients were assessed within 2 weeks of notification and annually thereafter. The ACR 1987 criteria for RA were applied at each assessment. Age- and sex-specific incidence rates were calculated. RESULTS: If up to 12 months elapsed from symptom onset to notification to NOAR and the ACR criteria were applied at the baseline assessment, RA incidence estimates, age-adjusted to the population of England and Wales, were 30.8/100,000 for women and 12.7/100,000 for men. If up to 5 years elapsed from symptom onset to notification, these estimates rose by 45% for women and 36% for men. If up to 5 years elapsed between symptom onset and notification and the criteria were applied cumulatively, the estimates rose by 75% and 93% for women and men, respectively, compared with the 1-year data, reaching 54.0/100,000 for women and 24.5 per 100,000 for men. CONCLUSION: Accurate estimation of the incidence of RA requires long-term followup of patients who present with undifferentiated inflammatory polyarthritis. The highest age-adjusted estimates from this study are probably the best that are available.

Adolescent↗

PubMed1999

A semiquantitative whole genome screen analysis of alcohol dependence.

Two whole genome screens were applied to sibling pairs from the Collaborative Study on the Genetics of Alcoholism (COGA) family data to compare a semiquantitative method with a standard qualitative approach. The semiquantitative method used a score derived from 11 symptoms, and the qualitative approach used the COGA criteria for alcohol dependence. There was no concordance in the regions identified by the two models. Three regions of nominal significance were identified using the symptom score. In these three regions, correlated traits were also analyzed to determine whether linkage could be attributed to their intermediate effect. The evidence for linkage to one locus on chromosome 6 could be explained by linkage to the personality trait harm avoidance.

Alcoholism↗

PubMed1999

Diet and lifestyle characteristics associated with dietary supplement use in women.

OBJECTIVES: To describe the characteristics of dietary supplement users in a large cohort of women and test the hypothesis that supplement users would be more likely to have a healthier lifestyle than non-users. DESIGN: Comparison of nutrient intakes from food frequency questionnaire (FFQ) data for 8409 supplement users and 5413 non-users. Use of logistic regression modelling to determine predictors of supplement use in this cohort. SUBJECTS: 13,822 subjects from the UK Women's Cohort Study (UKWCS) for whom data on supplement use was available. RESULTS: Significant differences in nutrient intakes from FFQ were seen between the two groups, with supplement users having higher intakes of all nutrients, except for fat and vitamin B12. Use of dietary supplements was associated with being vegetarian, vegan or fish-eating, consuming more fruit and vegetables, being more physically active and having a lower alcohol intake. Supplement use was less likely in those with a body mass index above 25 and those who reported smoking regularly. CONCLUSIONS: The findings are consistent with the hypothesis that supplement use is associated with a healthier lifestyle profile and an adequate nutritional intake, suggesting that supplement users do not need to take supplements to meet a nutrient deficiency.

Adult↗

PubMed1999

Absence of association between interleukin 1 alpha and oligoarticular juvenile chronic arthritis in UK patients.

OBJECTIVE: To determine whether interleukin 1 alpha (IL-1alpha) polymorphisms are associated with UK oligoarticular juvenile chronic arthritis (JCA). PATIENTS AND CONTROLS: A well-characterized population of 164 UK Caucasian oligo-JCA patients and a control panel of 173 unrelated healthy UK Caucasian individuals. METHODS: The IL-1alpha promoter mutation at -889 was examined using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The cases and controls were also genotyped for an IL-1alpha intronic microsatellite repeat. RESULTS: No association was observed between IL-1alpha polymorphisms and UK oligoarticular JCA patients. In particular, no association between IL-1alpha polymorphisms and chronic anterior uveitis was found. CONCLUSIONS: IL-1alpha is not associated with oligoarticular JCA in UK patients. This differs markedly to findings for IL-1alpha in Norwegian JCA patients.

Adult↗

PubMed1998

The effect of number of days in culture and plasminogen activator inhibitor-1 (PAI-1) 4G/5G genotype on PAI-1 antigen release by cultured human umbilical vein endothelial cells.

An insertion/deletion (4G/5G) polymorphism in what has been shown to be an enhancer/repressor binding site in the promoter region of the PAI-1 gene has been related to plasma PAI-1 activity. Transfection studies demonstrated increased interleukin-1 stimulated PAI-1 synthesis in cells containing the 4G sequence. To study this response in endothelial cells, first passage HUVEC from 26 umbilical cords were stimulated with interleukin-1 and tumor necrosis factor-alpha. PAI-1 antigen was measured in 24-hour conditioned medium and allele-specific PCR utilized to determine genotype at the 4G/5G locus. Analysis of covariance was used to determine whether the effect of a variable time in culture was masking a difference between genotypes. A trend towards higher PAI-1 levels with increasing time in culture was observed. The geometric mean (95% confidence interval) of the basal rate of PAI-1 release was, 4G/4G 9.7 (7.0, 13.5) ng/24 hours (n=11), 4G/5G 9.5 (6.5, 13.9) ng/24 hours (n=9), and 5G/5G 10.9 (7.8, 15.1) ng/24 hours (n=6). In cells of the same cultures, the interleukin-1 stimulated levels were 25.9 (23.1, 29.1), 27.2 (23.6, 31.3), and 23.1 (19.5, 27.3) ng/24 hours, respectively, corresponding to ratios of stimulated to basal levels of 2.68, 2.87, and 2.12. After adjustment for time in culture the basal PAI-1 release was 4G/4G 10.7, 4G/5G 9.1, and 5G/5G 9.7 ng/24 hours. For interleukin-1 stimulated release the adjusted levels were 26.3, 27.0, and 22.7 ng/24 hours, respectively. Adjusted levels in 4G/4G genotype cells were non-significantly greater than those in cells of 5G/5G genotype by a factor of 1.16 (0.95, 4.08). This study did not demonstrate a significant difference in basal or cytokine stimulated PAI-1 release from cells of different PAI-1 promoter (4G/5G) genotypes but does not exclude increased interleukin-1 stimulated PAI-1 release in the 4G/4G compared with the 5G/5G genotype.

Analysis of Variance↗

PubMed1998

Nitrate in drinking water and the incidence of gastric, esophageal, and brain cancer in Yorkshire, England.

OBJECTIVES: This small-area ecologic study in Yorkshire, northern England, examines the hypothesis that exposure to higher levels of nitrate in drinking water increases the risk of stomach, esophageal, or brain cancer in adults. METHODS: Nitrate levels over the period 1990-95 and numbers of incident cancers from 1975-94 were available for 148 water supply zones, geographically defined areas each supplying water of homogeneous chemical composition to an average population of around 20,000. RESULTS: No relationship was found between nitrate concentrations and the incidence of stomach or esophageal cancers. The incidence of cancer of the brain and central nervous system was found to be higher in areas with higher nitrate levels, with a relative risk of 1.18 (95 percent confidence interval = 1.08-1.30) in the quartile of the population with the highest average levels (mean 29.8 mg/l) compared with the lowest quartile (mean 2.4 mg/l). The increase in risk remained statistically significant (P < 0.01) after allowing for other covariates and for extra-Poisson variation in a regression model. CONCLUSIONS: This study does not support the hypothesis of an increased risk of stomach or esophageal cancer associated with higher nitrate levels in drinking water. The observed relationship with brain cancer requires confirmation in other studies, including those involving data on individuals.

Adolescent↗

PubMed1997

Using cross-check questions to address the problem of mis-reporting of specific food groups on Food Frequency Questionnaires. UKWCS Steering Group. United Kingdom Women's Cohort Study Steering Group.

OBJECTIVE: To explore the potential mis-reporting of specific food groups from food frequency questionnaire (FFQ) data and to examine the effect of using a weighting factor on estimated nutrient intake and ranking of subjects within the cohort according to nutrient intake. DESIGN AND SUBJECTS: A weighting factor was calculated for each of the individual 6572 women aged 35-69 y for four food groups, fish, meat, vegetables and fruit, using FFQ data and cross-check responses. RESULTS: The vegetables weighting had most effect on median intakes, particularly of fibre, vitamins A, C and E and folate. When all the weightings were applied, the median intakes of vitamins A and E were reduced by 35% and 27% respectively and the vitamin C intake was reduced by 44%. Ranking of subjects within the cohort according to nutrient intake was barely affected by the fish and meat weightings. The vegetable weighting had most effect on vitamin A with a rank correlation coefficient of 0.88. When all the weightings were applied the rank correlations for vitamins A, C and E and folate were all less than 0.90. CONCLUSION: Inclusion of cross-check questions in FFQs can provide an additional source of information on food group intake. This can be compared with FFQ data to help identify possible over-reporting and then to adjust frequency of intake accordingly.

Adult↗

PubMed1997

von Willebrand factor and factor VIII: C in acute cerebrovascular disease. Relationship to stroke subtype and mortality.

BACKGROUND: Elevated von Willebrand factor (vWF) is a risk factor in the development of acute myocardial infarction. The importance of vWF and factor VII:C in the pathogenesis of cerebrovascular disease (CVD) is poorly defined. METHODS AND RESULTS: We studied 208 cases of stroke whose pathological type was defined by cranial computed tomography. Cerebral infarcts were grouped according to the Oxfordshire Community Stroke Project (OCSP) clinical classification. The results in patients were compared with 184 healthy reference subjects. In patients, vWF and FVIII:C levels were determined initially and after three months. Patients were followed prospectively for six months or until death. Levels of vWF and FVIII:C were elevated initially (1.86 IU/ml and 2.20 U/ml respectively) and after 3 months (1.51 IU/ml and 1.90 U/ml) compared with a healthy reference population (1.26 IU/ml and 1.49 U/ml p = 0.0001). In the initial sample, vWF was associated with age (p = 0.01). FVIII:C was related to age (p = 0.04), gender (p = 0.007 higher for females) and a history of diabetes mellitus (2.56 U/ml vs. 2.16 U/ml in non-diabetics, p = 0.008). Initial vWF levels were higher in subjects with large vessel disease (TACI/PACI) group compared with the small vessel disease (LACI) group [2.12 IU/ml, (n = 112) vs. 1.48 IU/ml (n = 59) respectively, p = 0.0001] and similarly in initial FVIII:C levels (2.43 U/ml vs. 1.87 U/ml, p = 0.0001). Analysis of six-month case fatality, vWF levels were associated with risk of death [p = 0.01, OR 1.73 (1.12, 2.66) for an increase of I U/ml], even after allowing for stroke type. CONCLUSION: The relationship of vWF with stroke mortality has not previously been described. Although we have not demonstrated a causal role for vWF in the pathogenesis of CVD, elevated circulating levels of vWF may be associated with increased risk of death following stroke. A prospective study would be required to establish whether vWF is predictive for the development of CVD.

Acute Disease↗

PubMed1996

Commingling analysis of the distribution of a phenotype conditioned on two marker genotypes: application to plasma angiotensin-converting enzyme levels.

Commingling analysis is a statistical method for distinguishing between one (usually normal) distribution and a mixture of two or more distributions. It is used in genetic studies, since one mechanism giving rise to a mixture of distributions is the effect of a major gene. Plasma levels of angiotensin-converting enzyme (ACE) have been shown to be related to an insertion/deletion (I/D) polymorphism in the ACE gene. Recently, Cambien et al. [(1994) Circulation 90:669-676] used commingling analysis in a study of ACE, extending the method to condition on information about the I/D polymorphism in the gene. A further common polymorphism has been discovered recently by our group [Foy et al. (1995) Blood Coagulation Fibrinolysis 6:590] in the promoter region of the gene. In this paper we extend the method of commingling analysis to condition on two marker loci. The method is illustrated by application to plasma ACE levels in subjects for whom genetic information at both the I/D and promoter loci has been recorded. The results confirm strong evidence for a mixture of three normal distributions in preference to one or two, and also show that neither polymorphism is identical to a putative functional polymorphism. To assess the performance of the method, a simulation study was carried out. Parameters may be estimated more efficiently conditioning on two marker loci than on one or none, but this is not always the case if the underlying distributions are well separated. Conditioning on marker loci can increase the power to distinguish between alternative hypotheses of interest.

Adult↗