Biomedical subjects
Publications and source records attributed to C G Barnes.
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.
Reappraisal of disease-modifying antirheumatoid drug (DMARD) therapy in rheumatoid arthritis (RA) has raised the possibility that the risks of treatment outweigh the benefits. To provide more information a retrospective survey of the case-notes of 325 patients with RA was performed. The case-notes were randomly selected from the 2320 RA patients indexed in one department. Improvement was defined by the contemporary written notes of the managing physician. Analysis employed the life-table technique. A total of 247 case-notes could be adequately analysed: 154 patients had received one or more DMARDs constituting 251 drug-patient exposures. Improvement followed drug-patient exposure in 57% of cases after a delay of between one and seven months. Nine per cent occurred within one month and 22% within two months. Of those patients withdrawn from treatment after less than two months, the 'early withdrawal' group, 25% subsequently improved without further DMARD therapy. The probability of still receiving a specific DMARD 8 months, 24 months and 36 months after the start of treatment was 50%, 25% and 10%, respectively. The majority of withdrawals resulted from adverse reactions. There was no evidence for a relationship between patient responses to sequential DMARDs.
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.
The validity of the antidromic method in the measurement of median and ulnar sensory nerve conduction is determined. Analysis of our results show that both the orthodromic and antidromic methods provide consistent results. Both methods were accurate in diagnosing Carpal Tunnel Syndrome (CTS), with an upper limit of normal for distal sensory latency of 4.5 msecs motor, and 4.0 msecs sensory in the median nerve. Variation with age and sex was studied. Latency when measured by either method showed no variation. Amplitude showed a consistent decrease with age. No sex difference was detected. We conclude that the antidromic stimulatory method is accurate, reproducible, and convenient, and therefore is at least as good if not better than the orthodromic method in the context of a busy routine electrodiagnostic clinic.
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Judgments of "current disease activity" made on "paper patients" (patient data presented on simple forms) reflect those made when seeing the real patients on whom the "paper patients" are based (R = 0.853) and furthermore are highly reproducible (R = 0.952). Judgments made on the same "paper patients" in a rheumatology department in the UK and one in Canada also correlate highly (R = 0.860) and this may reflect a common experience in the type of patients seen. Such general similarities between centers justify comparisons of more detailed analysis of clinical judgment using "paper patients."
Behçet's disease was associated with HLA-B5, DR5, and MT2 antigens in Japanese. No virus or other agent was clearly implicated. Pathologic studies showed brainstem strokes and gut perforation from discrete ulcers. There was a significant reduction in T4 inducer-helper lymphocytes. Immune complexes in serum were detected in 30 to 50% of patients, and antibodies to the glycolipid GA1 were found in 91% of patients with neurologic involvement. Although several neutrophil functions were enhanced, for example, chemotaxis, phagocytosis, and generation of oxygen intermediates, mononuclear cells seemed to be of primary immunopathogenic importance. Treatment with chlorambucil appeared superior to other reported treatments of uveitis and meningoencephalitis.
Thirty-eight of 58 patients with skeletal tuberculosis (TB) reviewed were immigrants and 20 were of British indigenous origin. Spinal involvement i 28 cases was less common than involvement of peripheral joints, bones, or tendon sheaths (30 cases). Predisposing factors, including previous TB, were present in 70% of British patients and 31% of immigrants. Follow-up study of 23 cases showed that a complete clinical recovery of the skeletal disease was more likely in immigrants than indigenous cases and also in cases referred to hospital early. Immigrants presented usually within 5 years after arrival in Britain and at a younger age than indigenous cases; a quarter had within 5 sites of infection outside the skeletal system. Skeletal tuberculosis in the indigenous population remains very uncommon, and in half of these cases a history of previous TB was given. The need for continued awareness of skeletal TB is stressed, especially in immigrants, and also the importance of early diagnosis and institution of appropriate therapy.
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A five-centre double-blind crossover trial of two two-week periods using diclofenac and indomethacin showed that both drug groups (51 patients) with rheumatoid arthritis responded similarly in relation to pain scores and morning stiffness. It was noted that the response was better in inpatients than in outpatients, despite differences in disease severity. In the osteoarthritis trial (58 patients) it was shown that neither drug significantly reduced resting pain, although both drugs were significantly better in reducing pain on movement; however, patient preference was for diclofenac. Three patients treated with indomethacin withdrew owing to side-effects, compared with one on diclofenac. A slight but significant decrease in haemoglobin levels was observed in both treatment groups with osteoarthritis, but this did not appear to be symptom-related.
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Eight specimens of synovial membrane from 6 patients with 'definite' Behcet's syndrome were available for histological examination. Only the superficial zones of the synovia were affected, all except one being replaced by dense inflamed granulation tissue composed of lymphocytes mingled with macrophages, vascular elements, fibroblasts, and neutrophils. There was a marked plasma cell infiltrate and lymphoid follicle formation in one synovium only, and there was no evidence of infection. Pannus and erosive change were present in the three specimens which included the articular surface, the erosive change being visualised radiologically in two of these. It is suggested that these appearances are characteristic of Behcet's syndrome and should be added to the list of diagnostic criteria.
Four patients with Felty's syndrome developed massive upper gastrointestinal bleeding due to oesophageal varices. The underlying hepatic pathology in all 4 was nodular regenerative hyperplasia. This appears to be a difficult histological diagnosis to make, having been initially reported as normal on percutaneous biopsy or as fibrosis or cirrhosis on wedge biopsy. This series brings the total number of cases reported in the English literature of this association to 12, suggesting a definite symptom complex. The portal hypertension seems to be due to a combination of increased splenic blood flow and postsinusoidal resistance. The clinical importance of this syndrome is that the appropriate therapy for bleeding oesophageal varices appears to be shunt procedure such as a splenorenal shunt with splenectomy, which should be well tolerated.
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