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Biomedical subjects

A Silman

Publications and source records attributed to A Silman.

At least 109 records · Page 6Linked to original sources

The prevalence of chronic widespread pain in the general population.

OBJECTIVE: To establish the prevalence of chronic widespread pain and associated symptoms in a general population sample. METHODS: Cross sectional postal survey of 2,034 adults in the north of England. RESULTS: The point prevalence of chronic widespread pain was 11.2%. The symptom was strongly associated with other somatic complaints and with measures of depression and anxiety. CONCLUSION: In the general population, this cardinal symptom of fibromyalgia is common and identifies a group who are more likely also to report symptoms of fatigue and depression.

Adolescent↗

Timing of pregnancy in relation to the onset of rheumatoid arthritis.

The interval between the onset of rheumatoid arthritis (RA) and the most recent pregnancy prior to RA onset in 88 women was determined. These data were compared with data obtained from a group of 144 age-matched normal women (controls) who had been assigned a "dummy date for RA onset" for the purposes of analysis. The frequency of disease onset during 3 time intervals within the period from conception to 1 year postpartum was compared with the frequency of disease onset outside this period. There was a reduction in the incidence of disease onset during pregnancy (adjusted odds ratio [OR] 0.30, 95% confidence interval [CI] 0.04-2.6) and a numerically greater increased risk of RA onset during the first 3 months postpartum (OR 5.6, 95% CI 1.8-17.6), which persisted for the subsequent 9 months (OR 2.6, 95% CI 0.8-7.9). A reduction in the incidence of disease onset was seen during all pregnancies; in contrast, the postpartum increase was greater in those with RA onset after the first pregnancy. The reduced incidence of RA onset during pregnancy, with the increased risk postpartum, mirrors the previously described suppression of disease activity during pregnancy and the subsequent flare postpartum in women with established RA. In addition, the increased postpartum risk after the first pregnancy might suggest that in susceptible women, either the hormonal changes or the exposure to the fetus's paternal HLA might represent a risk factor for disease causation.

Adult↗

Reliability of skin involvement measures in scleroderma. The UK Scleroderma Study Group.

Two methods have been proposed to quantify the extent of skin involvement in scleroderma. These are (1) a scoring system which quantifies and summates this severity rating in 17 areas of skin surface and (2) a method estimating the percentage of skin involvement using a shaded manikin. We report on a study comparing the inter-observer reliability of these two approaches using the ratings of six clinicians on 12 patients. Systematic bias between observers was noted with both methods, but inter-observer agreement, as-assessed by the intraclass correlation coefficient (ICC), was higher with the score method. The manikin method resulted in a greater degree of disagreement between the observers, as well as a higher amount of random error, reflecting the difficulty of defining the bounds of abnormal skin. Despite the presence of bias, the score method is the preferred method for assessing the level of skin involvement.

Analysis of Variance↗

Prevalence of symptoms of Raynaud's phenomenon in general practice.

OBJECTIVE: To investigate the prevalence of Raynaud's phenomenon in the populations of five general practices. DESIGN: Two populations studied. A questionnaire was given to all new patients attending five general practices over four weeks, and the same questionnaire was sent by post to a random sample of adults from two of the practices. SETTING: General practices in inner London, Merseyside, and Cheshire. SUBJECTS: 1532 Patients who completed questionnaires (1119 who attended the surgeries (response rate unknown) and 413 respondents to the postal survey (response rate 69%)). MAIN OUTCOME MEASURES: Response to questionnaire on symptoms of Raynaud's phenomenon: patients were regarded as having the disease if they had episodes of blanching of the fingers that were precipitated by cold and accompanied by sensory symptoms (pins and needles or numbness). Subsequent interview and clinical appraisal of patients with the disease according to their responses to the questionnaire. RESULTS: The prevalence of Raynaud's phenomenon was 11% (26/231) and 19% (34/182) respectively in men and women who completed the postal questionnaire and 16% (56/357) and 21% (157/762) respectively in those who completed the questionnaire when attending their general practice. Thus the overall rates were slightly higher in women, but there was no effect of age even after adjustment of the rates for practice and method of survey. CONCLUSION: The prevalence of Raynaud's phenomenon is high compared with the low number of patients who seek treatment for the disease.

Adolescent↗

Locomotor disability in very elderly people: value of a programme for screening and provision of aids for daily living.

OBJECTIVE: To assess the prevalence of potentially reversible locomotor disabilities in elderly subjects and the cost effectiveness of providing aids for daily living. DESIGN: Population based randomised controlled trial of subjects aged greater than or equal to 85 living independently in an inner London borough. SETTING: 21 Electoral wards of the London Borough of Hackney. SUBJECTS: 1255 Subjects aged greater than or equal to 85 living in their own home whose names were obtained from general practitioner lists and cross checked against the electoral register, 511 of whom were subsequently found to be ineligible. Of the 744 remaining, those with disability on screening were randomised and allocated to an intervention group (36) or a control group (43), in which intervention was postponed until four weeks, after the follow up assessment. Subjects with aids supplied previously were excluded from the intervention phase. INTERVENTIONS: Provision of raised toilet seat, teapot tipper, tap turner, shoe horn and elastic laces, and double handled saucepan. MAIN OUTCOME MEASURES: Degree of difficulty (grades 1-4) with specific tasks (getting on and off a toilet, pouring from a teapot into a cup, turning taps on and off, carrying a saucepan of standard weight, and putting on shoes) and time taken to perform them. RESULTS: 545 (73%) Of the 744 eligible subjects assessed; 428 had no disability and 118 had difficulty with at least one task. Some had had their disability recognised before the study and already had aids, representing half of those with difficulty getting on and off the toilet but 24% for putting on shoes and 13% for pouring from a teapot and turning on a tap. The mean number of difficulties was similar between the groups (intervention group 1.7, control group 1.6). Time taken to complete the tasks corresponded with the observed grade of difficulty. All aids were associated with reduced difficulty according to observer assessment (% improvement intervention group v control group: raised toilet seat, 71 v 13 teapot tipper 100 v 33; tap turner 100 v 0; saucepan 88 v 0; shoe horn 50 v 13) and time taken to complete the tasks. A cost benefit analysis of this screening-intervention programme suggested a total cost of 32 pounds per individual benefit. CONCLUSIONS: Appreciable degrees of unrecognised locomotor disability are detected on screening of very elderly people living independently. Providing aids offers a feasible and cost effective means of improving function in such people.

Activities of Daily Living↗

A controlled trial of azathioprine in Behçet's syndrome.

Cytotoxic agents have long been used in Behçet's syndrome, especially for eye involvement, but their effectiveness has been uncertain. We conducted a two-year randomized, placebo-controlled, double-blind trial of azathioprine (2.5 mg per kilogram of body weight per day) in Turkish men with Behçet's syndrome without eye disease (group 1; n = 25) or with eye disease (group 2; n = 48). Corticosteroid treatment remained available to all the patients. All six patients withdrawn from the study because of severe eye disease were receiving placebo (P less than 0.001). Azathioprine was superior to placebo in the prevention of new eye disease in group 1 (1 vs. 8 patients; P less than 0.01) and in group 2 among the 14 patients who at entry had disease in only one eye (P less than 0.001). There were fewer episodes of hypopyon uveitis (1 vs. 15; P less than 0.001) among the group 2 patients who took azathioprine. The patients taking azathioprine also had less frequent oral ulcers, genital ulcers, and arthritis. There were no serious side effects attributable to azathioprine. We conclude that azathioprine is effective in controlling the progression of Behçet's syndrome, especially its most serious manifestation, eye disease.

Adult↗

Factor VIII related antigen in connective tissue disease patients and relatives.

This study assayed serum levels of FVIII Rag as a marker of endothelial injury in patients not only with frank connective tissue disease but also in those presenting with Raynaud's phenomenon and in families of those with systemic sclerosis. Elevated levels of FVIII Rag were found in 62% of patients with systemic sclerosis (SS), 38% with systemic lupus erythematosus (SLE), 67% with mixed connective tissue disease (MCTD) and in 17% with primary Raynaud's phenomenon. Twenty per cent of first degree relatives of patients with SS also demonstrated high levels of FVIII Rag and certain antibodies, namely those reacting with U1RNP and the centromere. The association between elevated FVIII Rag and antibodies linked to Raynaud's and vasculitis lends support to antibody involvement in pathogenesis. High levels of FVIII Rag in family members may reflect an increased susceptibility of endothelium to injury particularly since relatives also have a higher frequency of clinical features such as Raynaud's phenomenon.

Antibodies↗

Estimating the incidence of systemic lupus erythematosus in a defined population using multiple sources of retrieval.

We studied the age-specific incidence of SLE in a defined population in southern Sweden during 1981-86. Female incidence was 5.4/100,000/year and male incidence 1/100,000/year. In comparison with previous studies, incident cases were characterized by a high age at diagnosis with the highest incidence in age groups 55-64 and 65-74, approximately 7.5/100,000/year. The incidence was low in children under 15 years of age, 0.4/100,000/year, and unexpectedly so in the 15-24 decade, 1.2/100,000/year. Patient retrieval was based on four separate sources: a computerized diagnosis register; referrals from both public health care physicians and private practitioners; and records of ANA positive individuals from the single laboratory serving the area. All incident patients were present in at least two of these sources and 11 patients were present in three. We interpret the high amount of overlap between retrieval sources, without patients detected in only one source, as evidence for a high degree of completeness in our retrieval of SLE patients.

Adolescent↗

HLA class III haplotypes in multicase rheumatoid arthritis families.

The class III complement proteins (C2, BF, C4A, and C4B) were studied in 57 multicase rheumatoid arthritis (RA) families. When the gene frequencies for RA probands were compared to a normal control panel (162 haplotypes), a significantly higher frequency of the rare variant C4B*3 was observed (p less than 0.05). No significant differences were seen for the other C2, BF, C4A, or C4B alleles. The most common haplotype found in the probands was HLA-Cw5,B44,C2*C,BF*S,C4A*3,C4B*3,DR4, occurring with a frequency of 0.088. Haplotypes containing HLA-DR4 and Bw62 were found to carry either C4A*3,C4B*3; C4A*3,C4B*1; or C4A*4,C4B*2. When only haplotypes containing DR4 were compared between probands and controls, the frequency of the C4B*3-bearing haplotype remained higher in the probands. It is concluded that Bw62,C4A*3,C4B*3DR4 is a haplotype which is especially associated with RA. The low frequency in the RA population of this haplotype indicates that C4B*3 has a minor role in overall RA susceptibility.

Alleles↗

Co-segregation of HLA and rheumatoid arthritis in multicase families.

Inheritance of parental HLA haplotypes was examined in the offspring of 95 multicase rheumatoid arthritis (RA) families. Overall, in these families there was no evidence of preferential transmission of one parental haplotype, although this might have been expected given the loading of these families with RA cases. However, there was a difference in inheritance when the affected and non-affected offspring were compared. A co-segregation analysis showed that the inheritance of parental HLA haplotypes was different between the affected and the unaffected offspring. Unlike a previous report, no difference was demonstrated in this study between the offspring of affected and non-affected parents. Similarly, the affected offspring of HLA DR4 heterozygote parents were more likely to inherit HLA DR4 than the non-affected offspring. It is concluded first that linkage studies of RA using the affected sib-pair method are not invalidated, which would have been the case in the presence of preferential transmission of HLA to all offspring. Secondly, HLA and specifically HLA-DR4 does co-segregate with RA, and, finally, parental RA status, independent of DR4, has little influence in explaining the genetic susceptibility to RA.

Arthritis, Rheumatoid↗

HLA-DR4 associated Dw types in rheumatoid arthritis.

Frequencies of HLA-DR4 and its related Dw types were compared between randomly selected normal controls and the index cases of multiplex rheumatoid arthritis (RA) families. A DR4 frequency of 68.3% was observed in index cases (n = 57) compared to 31.2% in normal controls (n = 96). Cellular typing with homozygous typing cells (HTCs) revealed significant increases of Dw4 (49.1% vs 22.9% RR = 3.2 p less than 0.001) and Dw14 (22.8% vs 2.1% RR = 13.9 p less than 0.001) in the index cases. A non-significant increase was seen for Dw13 (8.8% vs 4.1%). When DR4 positive patients and controls were compared, a significant increase was seen only for Dw14 (34.2% vs 6.6% RR = 7.3 p less than 0.01). Data from HLA genotyped RA and normal families allowed an examination of haplotype combinations of HLA-B antigens and DR4/Dw types to be made. HLA-Dw4 was predominantly found with B44 and Bw62 with nearly all DR4/Bw62 haplotypes being Dw4 positive. HLA-Dw13 was associated with B44 and Dw14 with Bw60, B44 and B27. Based on HTC and normal family data. Dw10 was found to be strongly associated with B38 containing haplotypes. Analysis of 69 C4A, C4B complement typed DR4 haplotypes failed to show any statistically significant association between Dw type and "complotype". However, there was a suggestion of C4A3. BQO being associated with Dw4 (34.2% vs 16.1% X2 = 2.9 p = ns) and C4A3, B1 with Dw14 (45.5% vs 27.6% X2 = 2.1 p = ns).(ABSTRACT TRUNCATED AT 250 WORDS)

Arthritis, Rheumatoid↗

Accuracy of electoral registers and Family Practitioner Committee lists for population studies of the very elderly.

STUDY OBJECTIVE: The purpose of the study was to assess the accuracy of Family Practitioner Committee (FPC) lists for identifying very elderly people registered with general practitioners. DESIGN: The accuracy of available FPC lists was checked against the most recent electoral register to determine which recorded individuals were still living at their FPC registered addresses. This was followed by a postal and home visit enquiry to validate the accuracy of the electoral register. SETTING: The study was carried out in the London borough of Hackney. PARTICIPANTS: The investigation was confined to persons aged 85 and over. RESULTS: Of a total of 3018 people listed as being 85 years or over by the FPC, 1183 (39%) were listed on the electoral register. Of these, 751 (63%) were living at their registered address, ie 25% of the people in the original FPC list. A further 154 (5%) of the original list were not recorded on the electoral register but were alive at the FPC recorded address. CONCLUSIONS: the use of FPC lists alone to identify the very elderly in an inner city population is too inaccurate to be of value. The combined use of FPC lists and the electoral register is better but one in six persons will still be missed.

Aged↗

An epidemiological study of scleroderma in the West Midlands.

A population based study of the occurrence of scleroderma was carried out on the 4.1 million adult residents of the West Midlands Region. Seven separate sources were used to obtain cases. This first epidemiological study of scleroderma in the UK suggests prevalence rates of 13 and 48 per million in males and females respectively, with annual incidence rates of 1 and 6 per million. The peak age of onset is between 45 and 54 but new cases continue to arise even during the eighth decade. There is a pronounced female excess, with a ratio of 6:1, this excess being particularly marked in those under 45. It is difficult to assess the completeness of notification and thus the estimates should be considered as minimum. There are, however, suggestions in these data that the completeness of recording was high.

Adolescent↗

Chromosome 14 markers in rheumatoid arthritis.

Phenotype frequencies for variants of the chromosome 14 markers, alpha 1 antitrypsin (protease inhibitor--Pi), and immunoglobulin heavy chain gene allotypes (Gm and Am) were examined in affected and unaffected members of multicase rheumatoid arthritis (RA) families and compared with published population data. Significantly higher frequencies of phenotypes containing Pi*Z and Pi*S were observed in unrelated index RA cases compared with UK population data. There was also a higher frequency of Pi*Z in family members without RA than in population controls but no such difference for the frequency of Pi*S. No difference in the frequency of PiM1M2 heterozygotes was seen between patients with RA and population controls. An examination of clinical data failed to show any relation between any particular feature of RA and positivity for Pi*Z or Pi*S. No significant differences in frequency of Gm phenotypes were observed between patients with RA and controls. Significant association was found, however, between Pi*Z and Gm phenotypes containing Gm(zax;g). These associations are interpreted as indicating linkage disequilibria between these alleles. No interactions between DR4 and either G1m(z), (a), or (x) allotypes were apparent in patients with RA. A significant association was seen in the index RA cases between DR4 and Pi phenotypes carrying Z or S alleles. Observations from this study provide evidence for the existence of a genetic component for RA susceptibility encoded on chromosome 14. An interactive effect of these genes with DR4 towards susceptibility appears likely.

Arthritis, Rheumatoid↗

HLA: linkage with rheumatoid arthritis or seropositivity.

HLA haplotype sharing was compared in sibships from multicase families with rheumatoid arthritis (RA), subdivided by rheumatoid factor status, to investigate the claim that HLA is linked more to RA severity than susceptibility. Considerable deviation from expected (Mendelian) inheritance towards greater sharing of inherited parental haplotypes was observed in the sibships as a whole and when subdivided according to the serological status of the sibship's members. Further, there was no evidence that linkage was stronger in the seropositive concordant than in the other sibships. Linkage was also demonstrated between HLA and seropositivity even in sibships where not all members expressed clinical RA. These results, therefore, do not support the existence of genetic heterogeneity between seropositive and seronegative RA, a possibility previously suggested from population studies of antigen associations.

Antibodies↗

HLA and rheumatoid arthritis: a combined analysis of 440 British patients.

Four hundred and forty unrelated British Caucasoid patients with rheumatoid arthritis (RA) have been HLA typed for class I and class II antigens. Analyses of HLA antigen associations were performed on the overall group and in patient subsets selected according to particular disease parameters or sex, or both. The results confirm previously reported positive associations of HLA-DR4, Dw4, and DRw53 and negative associations of HLA-DR2 and DR7 with RA. Patients subsets with severe erosions, seropositivity, and features of extra-articular disease showed a stronger association, also confirming earlier reports. The link between HLA and disease severity was emphasised by a significant trend of increased Dw4 frequency with increasing severity of radiological erosions. In addition, a positive association of RA with HLA-A2 was observed and a strong negative association with DR3. The frequency of HLA-B27 was significantly increased in patients with subluxation of the spine. Differences were observed between male and female patients in relation to the HLA association. In men an increase in the frequency of the haplotype HLA/Dw4/DR4/Bw62/Cw3/A2 was observed. This showed no relationship with parameters of disease severity other than extra-articular disease. In women only class II antigens (DRw53/Dw4/DR4) showed an increased frequency. This increase was strongly associated with disease severity. A significant decrease of this class II association was observed with increasing age of disease onset; this was not seen in men.

Adolescent↗