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Biomedical subjects

A Silman

Publications and source records attributed to A Silman.

At least 73 records · Page 4Linked to original sources
PubMed1998

Low frequency of recent parvovirus infection in a population-based cohort of patients with early inflammatory polyarthritis.

OBJECTIVE: To determine the contribution of human parvovirus B19 infection in explaining the incidence of early inflammatory polyarthritis (IP) in a population. SETTING: The Norfolk Arthritis Register (NOAR) is a community-based programme aiming to ascertain all new cases of IP arising in a population that lead to attendance at primary care. SUBJECTS: 147 newly ascertained subjects with IP with a disease duration of less than 16 weeks. METHODS: Full clinical appraisal of all subjects who were followed up for three years. B19 IgM assayed with a third generation antibody capture enzyme immunoassay. RESULTS: Only four (2.7%) patients had evidence of recent B19 infection, only one of whom did not satisfy criteria for rheumatoid arthritis (RA). CONCLUSION: B19 infection does not explain more than a small proportion of either RA or undifferentiated IP cases occurring in the population.

Adolescent↗
PubMed1998

Association between amputation, arthritis and osteopenia in British male war veterans with major lower limb amputations.

OBJECTIVES: To investigate the association between amputation, osteoarthritis and osteopenia in male war veterans with major lower limb amputations. Specific questions were to determine whether lower limb amputees following trauma are at subsequent risk of developing osteoarthritis (OA) and osteoporosis of the hip on both the amputated and nonamputated sides. DESIGN: Retrospective cohort study in British Male Second World War veterans with major unilateral lower limb amputations. SUBJECTS: Seventy-five male Second World War veterans with major lower limb amputations known to be alive were invited to participate from a subregional rehabilitation centre. After exclusions, 44 agreed to attend for examination and radiological screening. METHODS: The presence of hip OA was determined from a single anterior posterior pelvic X-ray using two approaches: minimum joint space and the Kellgren and Lawrence (K&L) scoring system. Bone mineral density (BMD) was measured by a dual energy X-ray absorptiometry (DXA) scan and prosthetic rehabilitation outcome measures were recorded. RESULTS: Twenty-seven (61%) hips on the amputated side and 10 (23%) on the nonamputated side were positive for OA (based on Kellgren and Lawrence grade of >2). Using a minimum joint space threshold of below 2.5 mm, 24 (55%) hips on the amputation side and 8 (18%) on the nonamputated side were also positive for OA. There was a threefold increased risk of OA for those with above-knee compared to a below-knee amputation. By contrast, from published general population surveys only 4 (11%) cases of hip OA would have been expected on both the amputated and nonamputated hips. There was a significant decrease in femoral neck BMD in the amputated side (p <0.0001) and significantly lower BMD in above-knee amputees than in below-knee amputees (p = 0.0027) as compared to normal age- and sex-matched population. CONCLUSION: Male war veterans with unilateral major lower limb amputations develop significantly more osteoarthritis of the hip than expected on both ipsi- and contralateral sides. Amputation was also associated with loss of bone density. Above-knee amputees develop significantly more hip osteoarthritis and osteopenia of greater severity in the amputated side than below-knee amputees.

Aged↗
PubMed1998

Assessment of functional ability in patients with scleroderma: a proposed new disability assessment instrument.

OBJECTIVE: To develop a simple assessment of functional ability in patients with scleroderma and to examine its reliability both as a patient self-administered instrument and when administered by a trained observer. METHODS: An 11 item, 4 grade, functional assessment questionnaire was developed after extensive consultation with patients, physiotherapists (PT), and occupational therapists (OT) with the aim of including all functional areas of relevance. The instrument was self-administered by patients after an interval of 7 days. In the interval, the patients were assessed using the same instrument by direct observation from both a PT and an OT. Forty-seven patients with scleroderma, of varying severity, were recruited from 2 centers. Results were similar for both centers and data were pooled for analysis. RESULTS: Agreement between the patients' first and 2nd assessment was good for all questions (estimated kappas 0.69 to 0.94) with no evidence of an order effect. Agreement was also good between therapists (estimated kappas 0.47 to 0.81). There was poor agreement between patients and therapists, with patients rating their disability substantially higher compared to the standardized therapist assessment. CONCLUSION: This assessment schedule has high face and content validity and has excellent reliability both between trained therapists and within patients over a short time period. Its administration either as a self-report or by a therapist depends, in part, on the type of investigation undertaken.

Disability Evaluation↗
PubMed1997

Allelic markers close to prolactin are associated with HLA-DRB1 susceptibility alleles among women with rheumatoid arthritis and systemic lupus erythematosus.

OBJECTIVE: To investigate linkage disequilibrium between HLA-DRB1 disease susceptibility alleles and microsatellite markers close to the prolactin gene, among women with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) and normal controls. METHODS: DNA from 89 women with RA, 76 women with SLE, and 94 controls was typed for HLA-DRB1 status and D6S422 and D6S285, 2 highly polymorphic microsatellite markers close to the prolactin gene. RA patients were stratified by DRB1*0401 status, and SLE patients were stratified by *0301 status. RESULTS: There was an excess frequency of D6S422*1 among SLE patients with DRB1*0301 (odds ratio [OR] 3.1). The frequency of this allele was also slightly in excess among RA patients with DRB1*0401 (OR 1.9). D6S285*5 was also in excess among female RA patients with DRB1*0401 (OR 3.5), and was slightly increased among female SLE patients with DRB1*0301. None of these alleles were found to be increased among *0401-positive or *0301-positive controls. CONCLUSION: These data indicate that there may be linkage disequilibrium between HLA-DRB1 alleles and microsatellite marker alleles close to the prolactin gene among women with RA and SLE. This suggests the possibility of extended haplotypes encoding for HLA-DRB1 susceptibility and high prolactin production, which contribute to susceptibility to both RA and SLE.

Alleles↗
PubMed1997

Oral contraceptives and rheumatoid arthritis: results from a primary care-based incident case-control study.

OBJECTIVE: The possibility that oral contraceptives offer a protective effect against the development of rheumatoid arthritis is still contentious. Of the 17 studies investigating this association, 11 have found a protective effect, and 6 have not. These differences are probably attributable to either selection or information biases in a subset of studies, although the exact reason is unknown. To overcome the methodological problems inherent in the design of previous studies, we have conducted a population-based case-control study. METHODS: Women who were incident cases of inflammatory polyarthritis, defined as swelling of at least two joint areas lasting at least 4 weeks, were recruited directly from primary care and compared with age-matched women from the same population. RESULTS: Cases and controls reported a similar level of "ever use" of oral contraceptives, adjusted odds ratio = 0.88 (95% confidence interval, 0.47, 1.64). The cases were, however, less likely to report using oral contraceptives at the time of onset, adjusted odds ratio = 0.22 (95% confidence interval, 0.06, 0.85). Similar results were observed for cases who satisfied the criteria for rheumatoid arthritis and cases who did not. CONCLUSION: These results indicate that only current oral contraceptive use protects against the development of inflammatory polyarthritis.

Adult↗
PubMed1997

Do new cases of rheumatoid arthritis cluster in time or in space?

OBJECTIVES: To examine for evidence of clustering in time, in space and in space/time in the occurrence of rheumatoid arthritis (RA). SETTING: A population-based incidence register of RA in the East Anglian region of the UK: population size 413,000. SUBJECTS: In all 687 new cases of inflammatory joint disease registered between 1 January 1990 and 31 December 1994 were studied. Population data were obtained from postcode areas by age and sex. ANALYSIS: Time trend analysis was conducted over the first 36 months and observed and expected distributions compared. Spatial clustering was based on comparison of observed distribution using map grid references to random expectation based on simulation. A similar procedure was undertaken for time/space clustering. RESULTS: There was no evidence of a time trend. There was only modest evidence of spatial clustering with non-random distribution observed in one area but there was no evidence of time/space clustering. CONCLUSION: Although a viral aetiology is the strongest candidate for RA, no evidence of a localized event in time was associated with disease development in this population.

Adolescent↗
PubMed1997

Linkage and association studies of the natural resistance associated macrophage protein 1 (NRAMP1) locus in rheumatoid arthritis.

OBJECTIVE: To determine if there is any evidence of linkage between the natural resistance associated macrophage protein gene, NRAMP1, and rheumatoid arthritis (RA). METHODS: Two dinucleotide markers, D2S1471, a highly polymorphic marker within 160 kb of NRAMP1, and a less polymorphic marker in the promoter region of NRAMP1, have been analyzed in 115 affected sib-pair RA families (35 with 2 parents, 18 with one parent) from the Arthritis and Rheumatism Council (ARC) National Repository and an additional 85 probands from the ARC National Twin Study and 96 controls. Individuals were typed for both markers by fluorescence based semiautomated polymerase chain reaction analysis. RESULTS: No evidence of increased allele sharing in affected sib-pairs was obtained using identity by descent (IBD), identity by state, and maximum likelihood score (MLS) analysis for the whole data set. A significant increase in allele sharing was observed with marker D2S1471 (LOD 0.74; p 0.05) in the HLA discordant subgroup using IBD and MLS-IBD. No significant differences in allele frequencies were observed for any markers in the association study. CONCLUSION: In a subset of sib-pairs that shared one or zero HLA haplotypes, LOD scores suggestive of linkage were observed. This suggests a role for NRAMP1 polymorphism in a subset of patients who do not possess HLA susceptibility alleles.

Alleles↗
PubMed1996

A simple algorithm to predict the development of radiological erosions in patients with early rheumatoid arthritis: prospective cohort study.

OBJECTIVE: To produce a practical algorithm to predict which patients with early rheumatoid arthritis will develop radiological erosions. DESIGN: Primary care based prospective cohort study. SETTING: All general practices in the Norwich Health Authority, Norfolk. SUBJECTS: 175 patients notified to the Norfolk Arthritis Register were visited by a metrologist soon after they had presented to their general practitioners with inflammatory polyarthritis, and again after a further 12 months. All the patients satisfied the American Rheumatism Association's 1987 criteria for rheumatoid arthritis and were seen by a metrologist within six months of the onset of symptoms. The study population was randomly split into a prediction sample (n = 105) for generating the algorithm and a validation sample (n = 70) for testing it. MAIN OUTCOME MEASURES: Predictor variables measured at baseline included rheumatoid factor status, swelling of specific joint areas, duration of morning stiffness, nodules, disability score, age, sex, and disease duration when the patient first presented. The outcome variable was the presence of radiological erosions in the hands or feet, or both, after 12 months. RESULTS: A simple algorithm based on a combination of three variables--a positive rheumatoid factor test, swelling of at least two large joints, and a disease duration of more than three months--was best able to predict erosions. When the accuracy of this algorithm was tested with the validation sample, the erosion status of 79% of patients was predicted correctly. CONCLUSIONS: A simple algorithm based on three easily measured items of information can predict which patients are at high risk and which are at low risk of developing radiological erosions.

Adult↗
PubMed1996

Are both genetic and reproductive associations with rheumatoid arthritis linked to prolactin?

The risk of rheumatoid arthritis (RA) seems to be associated with reduced fecundity and with breastfeeding; these apparently contradictory risk factors can be explained by their association with high prolactin concentrations. The only consistent genetic association with RA is for genes encoded in the HLA complex, particularly HLA DR4. We have identified some data indicating that the effects of breastfeeding and nulliparity are modified by HLA DR4 status, suggesting an interaction between genetic and reproductive risk factors in the aetiology of RA. The prolactin gene is in close proximity to the HLA region on the short arm of chromosome six. We therefore propose the hypothesis that the associations between DR4 and reproductive risk factors in RA are due to linkage disequilibrium between DR4 and an abnormally regulated prolactin gene polymorphism.

Arthritis, Rheumatoid↗
PubMed1996

Maternal exposure to paternal HLA does not explain the postpartum increase in rheumatoid arthritis.

The postpartum period, particularly after the first pregnancy, represents a time of increased risk for the development of rheumatoid arthritis (RA). The present study was undertaken to investigate whether this increase in risk may be due to maternal exposure to fetally inherited paternal HLA-DR antigens that were either 1) similar to their own or 2) had an increased likelihood of being one of the two specific types, HLA-DR1 and DR4, implicated in the etiology of RA. We recruited 94 families where the mother had developed RA within 12 months of a pregnancy, and HLA typed the mother, father, and relevant child of each family. Mothers were not more likely to share HLA-DR genes with their partners than would be expected, and children whose parents shared one HLA-DR gene were not more likely to inherit the shared gene from their father as opposed to the non-shared gene. Further, those children whose fathers were heterozygous for HLA-DR1 or DR4 were not more likely to inherit these genes as opposed to the non-DR1/DR4 gene. In conclusion, maternal exposure during pregnancy to either fetally inherited paternal HLA-DR1 and DR4 genes or to paternal DR genes similar to their own does not appear to contribute to postpartum maternal susceptibility of RA.

Arthritis, Rheumatoid↗
PubMed1996

Survival following the onset of scleroderma: results from a retrospective inception cohort study of the UK patient population.

Scleroderma is a multisystem disease which in many populations is reported to have a substantially reduced survival. One problem with many of the published studies is the inclusion of patients with differing lengths of disease at baseline, with the possibility of left censorship bias. The aim was to determine the survival and its predictors in a cohort of scleroderma patients with new onset of disease. All 283 new patients referred to one of the authors (CMB) who had a reported disease onset after 1 January 1982 were studied. Detailed clinical and laboratory information at baseline and at 1 yr were extracted from the structured records. Vital status as at 1 December 1993 was determined using the UK's NHS Central Register. Expected numbers of deaths were obtained by applying local age and sex all-cause mortality rates. In total, there were 1871 person-years of follow-up with crude mortality rates of 3.9 and 2.6%/year, respectively, in males and females. The mortality rate remained approximately constant over the first 10 yr of follow-up. In comparison with expected survival, based on the age distribution of the cohort, there was an overall 4-fold increased mortality rate in this group which was higher in females [standardized mortality ratio (SMR) 4.6, 95% CI 3.2-6.2] than in males (SMR 3.2, 95% CI 1.8-5.0). Analysis of cause-specific mortality showed that 79% of the excess deaths were scleroderma related, but this proportion was substantially lower in males than in females (67% vs 83.9%). These data confirm the increased mortality rate associated with scleroderma, but these rates are lower than those reported from other centres. Females have a higher age-adjusted mortality which is reflected in the different pattern of mortality between the sexes.

Cohort Studies↗
PubMed1996

More pain, more tender points: is fibromyalgia just one end of a continuous spectrum?

OBJECTIVES: To investigate the hypothesis that fibromyalgia represents one end of a spectrum in which there is a more general association between musculoskeletal pain and tender points. METHODS: The subjects studied were 177 individuals selected from a population based screening survey for musculoskeletal pain. All subjects completed a pain mannikin and were examined for the presence of tender points at the nine American College of Rheumatology bilateral sites. RESULTS: There were moderately strong associations (odds ratios range 1.3-3.1) between the reported presence of pain in a body segment and the presence of a tender point within that segment. Further, there was evidence of a trend of increasing number of tender points with increasing number of painful segments. The reporting of non-specific pain, aching, or stiffness, was also associated with high tender point counts. CONCLUSION: This study illustrates that the association between tender points and pain is not restricted to the clinically defined subgroup with chronic widespread pain. Given that widespread pain and tender points have previously been linked with distress, this might reflect lesser degrees, or earlier phases of the somatisation of distress.

Chronic Disease↗
PubMed1996

Incidence of rheumatoid arthritis is not related to indicators of socioeconomic deprivation.

OBJECTIVE: To evaluate the role of socioeconomic factors in susceptibility to rheumatoid arthritis (RA). METHODS: A prospective population based register of inflammatory joint disease (NOAR) recruited 687 adults between 1990 and 1992, of whom 50% satisfied ARA criteria for RA at presentation. Using census data, social class specific incidence rates were calculated for both sexes. A correlation analysis was undertaken examining the association between incidence rates and 5 indicators of socioeconomic status. RESULTS: There was no trend of increasing incidence with declining social class. None of the 5 indicators examined showed any evidence of association with incidence (rs range 0.0-0.3). CONCLUSION: In contrast to the data on factors influencing outcome in established RA, the socioeconomic status variables examined did not explain susceptibility patterns in the population studied.

Adult↗