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This study investigated whether a modified Cold Provocation Test could distinguish between 86 normal subjects and 31 patients with Raynaud’s phenomenon or 59 with hand arm vibration syndrome (HAVS). Of the HAVS subjects, 56 were seen for medical reports as they were involved in litigation. Their assessments were done in a different location but the same protocol was used. A standardised cold stress was used to reduce the finger temperature to 15°C or less without inducing reflex hyperaemia. This test had acceptable repeatability for subjects without HAVS with an intra-class correlation of 0.7. Baseline temperature, temperature rise in the first 30 seconds and the time taken to rewarm by 5°C were measured. Patients with Raynaud’s phenomenon and HAVS had cooler hands than controls. HAVS patients rewarmed most in the first 30 seconds. Patients with Raynaud’s phenomenon take longer to rewarm by 5°C than controls or those with HAVS (P<0.001). A baseline difference of >7.5°C between the temperature of the digit and that of the room is unlikely to occur in patients with Raynaud’s phenomenon or HAVS. A temperature gain of ≥2.2°C in the first 30 seconds on rewarming combined with a low baseline temperature strongly suggests HAVS. This modified cold provocation test may differentiate between patients with Raynaud’s phenomenon, HAVS and controls but this observation requires independent verification in subjects not involved in litigation and tested in the same facility. [ABSTRACT FROM PUBLISHER]

The distribution of the HLA-DR allele frequencies of 105 RA patients has been compared with the expected distribution under recessive and dominant modes of inheritance using control data from 2041 controls and the antigen genotype frequency among patients methodology. The observed distribution was compatible with a recessive mode of HLA-linked inheritance in RA, with a dominant mode rejected, whether HLA-DR4 was considered alone, or HLA-DR4 and HLADRI were combined as if they were behaving as a single predisposing gene. Mean sibship concordance rates (MSCRs) were calculated for categories of proband HLA-DR genotypes. The highest MSCR was seen for HLA-DR4 homozygous probands, and the lowest for HLA-DR2 or 7/non-4 genotypes. These combined observations suggest that interactions between both inherited HLA-haplotypes are important in the predisposition to RA. [ABSTRACT FROM PUBLISHER]

One hundred and forty-two RA patients and 121 of their healthy same-sexed siblings were tested for antibodies (Abs) to by indirect immunofluorescence. Eighty-five individuals had active RA (CRP>10 mg/l) and 57 inactive RA. The anti- Ab titre in the active RA group was significantly higher than in the inactive RA and non-RA group (<0.0001 in both cases). Anti- Abs were significantly elevated in 30 individuals with active RA compared with their healthy HLA-identical same-sexed siblings (>0.001). In 42 HLA-DR4 positive and 15 HLA-DR4 negative active RA patients, the Ab titre was non-significantly higher in the former group. Anti- Abs were not significantly elevated in any of the groups. Longitudinal data on 36 RA patients demonstrated a significant positive correlation between changes in CRP and changes in antibody titres (=0.52, <0.001). These observations require an explanation. [ABSTRACT FROM PUBLISHER]

It has been suggested that polymer coating might retard jejunal absorption of 5-amino salicylic acid (5-ASA) and thus promote delivery to its colonic site of action. Twenty three patients with active (nine), or quiescent (14) ulcerative colitis were given either uncoated or coated 5-ASA (Asacol) 400 mg qds for one to three weeks, after which they ingested five 1.5 ml dialysis membrane sachets which were recovered from the stool in the next 72 hours. After one week of treatment the concentration of 5-ASA in the faecal dialysate, urine, and fasting plasma in those receiving the coated and uncoated preparations were respectively: 25.4 +/- 5.1 compared with 1.2 +/- 0.4 mmol/l (p less than 0.001); 0.34 +/- 0.21 compared with 0.70 +/- 0.29 mmol/24h (NS) and 11.1 +/- 4.2 compared with 0.07 +/- 0.03 mumol/l (p less than 0.02). Faecal excretion of the drug appeared to be greater in patients with active colitis than in those with quiescent disease. Thus coating with pH dependent methacrylic acid copolymer B is a very effective method of promoting delivery of 5-ASA to the colon, stool dialysate concentrations being 20 fold more than those in controls. Increased trough plasma concentrations in the polymer coating group probably reflect delayed intestinal absorption but no evidence of plasma accumulation after 21 days of therapy was found. [ABSTRACT FROM PUBLISHER]

We report a 6-yr follow-up study of an original population of 50 patients who had three or more major joints (hips and knees) replaced. Thirty-one of 32 surviving patients were still ambulant in the community, and all patients described significant pain relief. No RA patient was requiring permanent inpatient or residential care and the family remained the main social support. They remained a very disabled group with a median Health Assessment Questionnaire score of 2.75. Ten required revision surgery: three hips and seven knees; four patients required their fourth lower limb joint (hip/knee) replaced and seven patients required surgery to the upper limbs and nine feet during the follow-up period. The median 10-yr survival of hip and knee arthroplasties in multiple joint replacement (MJR) patients with RA was 90.5 and 78.6% respectively. There was an increased incidence of cervical myelopathy in MJR patients 16.9%. The mortality rate was higher than expected (standardized mortality ratio = 590) but the actual surgery was not implicated. MJR therefore appears to be a worthwhile policy, even at long-term follow-up. [ABSTRACT FROM PUBLISHER]

We have studied anti- antibodies (APA), isolation of , and their relation to various measures of RA disease activity. Seventy RA patients with a CRP>10 mg/l had higher APA titres than 17 RA patients with CRP≤10 mg/1 ( = 0.006), and 36 non-RA controls ( = 0.003). However, in a cross-sectional study of the RA group, there was no correlation between APA and a number of clinical and laboratory measures of disease activity, including the CRP and Stoke RA activity index. A longitudinal study showed no correlation between changes in these measures of disease activity and change in APA titre. We were unable to isolate in the urine or faeces of RA patients more frequently than controls, and the isolation of did not correlate with serum APA titres. Urinary APA was present in equal frequencies in RA and non-RA patients. NSAIDs, DMARDs and steroids did not appear to influence APA titres in the RA group. These results suggest that APA may act as an acute phase protein, distinct from CRP, but not correlating with RA disease activity in its broadest context. The fact that the antibody we are measuring binds to may be irrelevant, and the study does not support a role for in RA. [ABSTRACT FROM PUBLISHER]

Objective: To determine whether HLA exerts a variable influence on the predisposition of siblings of probands with clinically mild and severe rheumatoid arthritis (RA).Method: Calculation of crude and adjusted odds ratios for concordance rates in sibships sharing two, one and no HLA haplotypes with a proband with clinically mild and severe RA, and HLA haplotype sharing in multiply affected sibships in the same clinical groups.Results: Compared with a reference value of 1.0 in siblings sharing no HLA haplotypes with a proband with mild RA, siblings sharing two HLA haplotypes with a severely affected proband had a sibship concordance rate odds ratio of 9.7 (95% confidence interval 2.5 to 38.2). When adjusted for age, sex, and disease duration, the odds ratio was 7.6 (1.8 to 32.4). No other sibships showed concordance rates which were significantly higher than the reference group. HLA haplotype sharing in multiply affected sibships in which the proband had severe RA deviated significantly from random (two, one, and no HLA haplotypes shared: 53.3, 40, and 6.7%, respectively; expected 25, 50, and 25%), whereas in sibships of probands with mild RA they did not (14.6, 70.8, and 14.6%).Conclusions: In the predisposition of siblings to RA, sharing HLA haplotypes with a proband is only important if the proband has severe RA. Mild RA is not genetically linked to the HLA region. [ABSTRACT FROM AUTHOR]