Use of genetic typing versus other markers for predicting outcome in patients with inflammatory arthritis: comment on the article by Gough et al.
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Biomedical subjects
Publications and source records attributed to J N Fordham.
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Medical treatment of symptomatic osteoporosis is unsatisfactory. Treatment of patients with low bone density but without history of fracture includes hormone replacement therapy (HRT) which offers the prospect of reduced fracture risk. Dual energy X-ray absorptiometry (DXA) offers a safe and accurate technique available for the measurement of bone mineral density at a district general hospital level. All open access service providing densitometry measurements for general practitioners and hospital consultants was instigated at South Cleveland Hospital in February 1991. A major purpose of the service was to provide density measurements in order to 'inform' the discussion between the patient and doctor with regard to the use of anti-resorptive and other medical agents. We report our experience of operating such a service. The report analyses the main reasons for referrals. Nine hundred and thirty female subjects and 63 male subjects were scanned. The main reason for female referral were early menopause, consideration for HRT, personal history of fracture and family history of fracture--these account for 54.7% of all referrals. In men, there was a high incidence of fracture, back pain and the use of steroids given as reasons for referral. Sixty-seven per cent of patients were referred by general practitioners. Eighteen per cent of female lumbar spinal BMD values were between 1 and 2 S.D. below the Leeds normative mean and 9.0% below 2 S.D. Figures for the femoral neck were 22.0 and 9.0%.(ABSTRACT TRUNCATED AT 250 WORDS)
The case is reported of a patient who developed an acute arthropathy, which was initially diagnosed as acute septic arthritis. The true diagnosis of rat bite fever due to Streptobacillus moniliformis was delayed because of difficulty in growing the organism, which has fastidious growth requirements. The patient had no history of rat bite, which is the usual form of transmission of this disease.
Four cases of post-yersinial reactive arthritis are described. All patients presented with an acute lower limb arthropathy with features of an associated enthesopathy. Two patients had restriction of axial skeletal movements. Systemic features were prominent in three, including weight loss and malaise. Mean age of onset was 34 years. Three patients gave a history of antecedent diarrhoea within the previous month. Three patients had raised titres to Y enterocolitica type 0:3 (ranging from 1 in 320 to 1 in 2560) and one had raised titres to Y pseudotuberculosis type 2 at 1 in 640. Two of the three patients with Y enterocolitica reactive arthritis ran a chronic course with low grade arthropathy of lower limbs and back stiffness. One patient developed radiological sacroiliitis at two years, and two patients had an increased sacroiliac index, though x rays of the sacroiliac joints were normal. The patient with Y pseudotuberculosis reactive arthritis had a self limiting disease with spontaneous resolution over six months.
The concentration of IgA and titre of IgA antibodies to several Gram-negative bacteria were measured in the serum and parotid saliva of patients with AS and normal tissue-typed individuals. Salivary IgA and antibody levels in the patients were identical with the control population. The serum antibody level against Yersinia enterocolica 0:3 was slightly raised in patients but there was no difference in the reactions to Klebsiella oxytoca strain MX100 or Escherichia coli 0111.B4. The serum IgA level was elevated in patients with AS, irrespective of HLA B27. We conclude that this approach is unlikely to provide convincing evidence of a link between Gram-negative bacteria and ankylosing spondylitis.
A 49 year old man with rheumatoid arthritis developed a proliferative glomerulonephritis with progressive renal impairment during treatment with D-penicillamine. His renal function continued to deteriorate after the drug was stopped but improved after treatment with corticosteroids and azathioprine.
Although recurrent rheumatic fever in adults is uncommon and the recurrence rate declines with age and with the interval from the attack, we describe a patient who has had four attacks of rheumatic fever, two in childhood and two in adult life.
Skin hypersensitivity to needle puncture (pathergy test) together with a positive HLA B5 antigen has been reported as a diagnostic test for Behçet's syndrome (BS) in Turkish patients. We have studied the pathergy test by 2 methods in 7 healthy volunteers who have the HLA B5(Bw 51 split) antigen and 19 patients with BS. The test was negative in all the normal volunteers and only one of the 19 patients with BS had a positive test by one of the 2 methods. Cluster analysis of our patients and those reported from Turkey showed no difference in their clinical features. The positivity of the pathergy test, and hence its diagnostic usefulness, seem to differ between Britain and Turkey, and we conclude that this difference is not related to the possession of the HLA B5 (Bw 51 split) antigen.
Polymorphonuclear leucocyte (PMN) function was studied in 29 subjects with ankylosing spondylitis (AS). Of these, 20 were HLA B27+ve and 9 B27-ve. There were 30 controls and, of these, 15 were B27+ve. Random and directed cell migration was measured by 2 techniques: migration through a micropore filter and migration under an agar film. The chemo-attractant was either case in-activated serum or zymosan-activated serum. By both techniques directed motility was increased in subjects with B27 or with AS when compared to the B27-ve controls. This suggests that the disease AS and the possession of B27 are both associated with increased PMN motility.
The aim of this study was to determine whether polymorphonuclear leukocyte chemotaxis, adhesion, and electrophoretic mobility were altered in inflammatory bowel disease and whether such alterations could be related to prior ingestion of immune complexes. Polymorphonuclear leukocytes from patients with ulcerative colitis and Crohn's disease showed significantly impaired stimulated migration (P less than 0.05), increased adhesiveness (P less than 0.01 in ulcerative colitis, P less than 0.001 in Crohn's disease), and reduced electrophoretic mobility (P less than 0.02 in ulcerative colitis, P less than 0.001 in Crohn's disease) compared with healthy controls. The disease control of patients with rheumatoid arthritis demonstrated reduced stimulated migration (P less than 0.025) but normal adhesion. Preincubating normal cells in inflammatory bowel disease sera suggested that the altered migration and adhesion were due to circulating serum factors. Circulating immune complexes, detected by the C1q PEG binding assay, were present in 12.5% of patients with ulcerative colitis and 30% with Crohn's disease. Direct immunofluorescence of polymorphonuclear leukocytes suggested binding and/or ingestion of complexes in 57% of patients with ulcerative colitis, and 67% with Crohn's disease. There was a direct correlation between positive immunofluorescence and impaired cell migration in ulcerative colitis (P less than 0.05), but no such relationship was found in the other parameters of polymorph function.
We report 2 contrasting cases of a seronegative polyarthritis associated with angioimmunoblastic lymphadenopathy (AILD). Both cases were nonerosive, with symmetrical involvement of the elbows, wrists, knees, and ankles. In one the arthritis appeared concurrently with the main systemic manifestations of AILD. The second presented with polyarthritis 18 months before the onset of AILD. This patient received azathioprine for 11 months before developing AILD, which raises the possibility of this drug being the causative agent.
We have applied computer-linked image analysis to the measurement of polymorphonuclear leucocyte motility under agarose. A high degree of correlation was found between manual and machine values of cell numbers migrating and leading front measurements. This method permits a more complete analysis of cell motility than current methods. It is quick and reliable and allows cell distribution profiles to be studied.
Three aspects of polymorphonuclear leucocyte (PMN) function were studied in 19 patients with Behçet's syndrome (BS). By 2 different techniques directed motility was found to be increased. This increase was largely due to the subgroup of patients with ocular involvement. Counts of absolute numbers of cells migrating highlighted this finding. No difference was found in the phagocytic or adherent properties of PMN in Behçet's syndrome. Increased PMN motility in Behçet's syndrome may contribute to the expression of the syndrome. It remains to be tested whether altered PMN motility in this syndrome is genetically linked.
Tests for polymorphonuclear cell (PMN) chemotaxis, adherence, and electrophoretic mobility (EPM) were carried out on blood PMN isolated from 27 normal subjects, 16 patients with uncomplicated rheumatoid arthritis (RA), and 9 patients with Felty's syndrome. Chemotaxis was measured by a modification of the Boyden chamber technique, adherence by retention of cells on nylon fibre columns, and EPM in a cylindrical electrophoretic assembly. There was no significant difference between the chemotactic migration of normal and rheumatoid PMN as assessed by the leading front measurement. However, PMN from patients with Felty's syndrome showed significantly reduced chemotaxis (P less than 0.001). Computerised image analysis showed this impaired migration to be due to an overall reduction in cell motility rather than loss of a subset cells. Activated serum from patients with RA and Felty's syndrome were as good chemoattractants as activated pooled AB serum. There was no significant difference in the adhesiveness of PMN from normal persons and rheumatoid patients, though PMN from patients with Felty's syndrome did show a trend to lower adhesiveness. Both RA and Felty's syndrome patients had an increase in the proportion of PMN of lower surface charge than controls. Direct correlations were observed between cells of high surface charge and nonadhesiveness.
Polymorphonuclear leucocyte (PMN) function was studied in 7 healthy subjects before and after 5 mg of colchicine taken in divided doses over 24 hours. Mean adherence to nylon fibre colums fell from a pretreatment level of 51% to 33.6% by day 1, remained low (31.8%) at day 5, and returned to pretreatment levels only by about day 9. Random motility (agarose plate method) fell from 932 micrometers to 688 micrometers by day 1, but had returned to normal by day 5. Directed migration and the phagocytic index (opsonised Candida albicans method) were not affected by colchicine treatment. In this marked and prolonged reduction in PMN adhesion implies an influence on maturing PMN precursors in bone marrow. Adherence to nylon fibres may reflect in-vivo properties of PMN which are important in the pathogenesis of acute gouty arthritis.
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