Biomedical subjects
Publications and source records attributed to M M Steven.
Pancoast syndrome, which comprises a lower brachial plexus lesion and Horner's syndrome, usually results from local invasion beyond the confines of the lung by an apical lung carcinoma. Other causes are rare. We report the unusual occurrence of a case of Pancoast syndrome caused by a destructive sclerosing fibrosis after pulmonary Staphylococcus aureus infection.
A survey of the prevalence of chronic arthritic conditions was carried out on a population of 35,251 patients registered with 29 general practitioners in the highlands of Scotland. Symptomatic osteoarthritis had an overall prevalence of 65 per 1000 but rose from one in 20 of those aged 40-50 years to one quarter of those over 70 years of age. Rheumatoid arthritis was present in 5.5 per 1000 with a two to threefold female preponderance and there was an unexplained threefold difference between the regions with the highest and lowest prevalence. Seronegative arthritides were found in 2.1 per 1000, polymyalgia rheumatica/temporal arteritis in 1.2 per 1000, and gout in 3.4 per 1000. Juvenile chronic arthritis had a prevalence of 0.39 per 1000 (2.0 per 1000 in those aged 15 years and younger) and connective tissue disease 0.45 per 1000. There was considerable variation in the prevalence of inflammatory arthritis throughout the region. The highest prevalence of rheumatoid arthritis was 14.5 per 1000 women in one east coast area and the lowest 5.2 per 1000 women in the west. The difference did not seem to be due to misclassification. A consultant's review of a questionnaire sent to all except those with osteoarthritis changed the proportions of patients who could be confirmed to have the respective inflammatory arthritides (rheumatoid arthritis between 3.4 and 5.0 per 1000, seronegative arthritides 2.0 per 1000, juvenile chronic arthritis 0.52 per 1000), and a third of those diagnosed as having rheumatoid arthritis failed to meet hospital oriented diagnostic criteria.
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In this study we report on the preparation and application of pokeweed mitogen (PWM) conjugated to latex particles. This conjugate (PWM-latex) was prepared by incubation of PWM with latex particles in the presence of glutaraldehyde. The effect of the addition of PWM-latex to human peripheral blood mononuclear cells (PBMC) was fully comparable to the addition of PWM alone i.e. differentiation of lymphocytes into blast cells followed by proliferation of these blast cells as measured by DNA synthesis and total cell number. Electronmicroscopically PWM-latex was found to be taken up by monocytes within the first 24 h after addition. Although no direct interaction could be observed between PWM-latex and lymphocytes, the latter were found to differentiate into blast cells. Due to interactions of these blast cells with latex-containing monocytes, latex particles were obviously released from the phagocytes and close contacts between latex particles and blast cells were regularly seen. In addition, it was found that blast cells of T cell origin, as judged by their positive reaction with anti-T cell monoclonal antibodies, had taken up latex particles. Based on enzyme-cytochemical, functional and light microscopical studies, monocytes could not be detected in the PWM-latex-driven PBMC stimulation after 6 days. At the electronmicroscopical level evidence was found that the inability to demonstrate macrophages could be due to the release of the lysosomal enzyme content and of parts of the cytoplasm.
A detailed ultrastructural study was made of the synovial iron deposits in cases of haemophilic synovitis (HS), pigmented villonodular synovitis (PVNS), rheumatoid arthritis (RA), osteoarthritis (OA), seronegative inflammatory arthritis (SNA), and in controls, to investigate the relationship between iron deposits and tissue damage. Iron was seen by electron microscopy in about 75% of synovial lining cells in HS and PVNS but only in about 25% of synovial cells from cases of RA and SNA. In cases of OA and in controls iron deposits were scarce. The iron was usually deposited within pleomorphic siderosomes and in HS was most common in type A synovial cells. In contrast, deposits in all other cases were more common in type B cells, which were frequently the predominant cell type, and siderosomes were smaller, more homogeneous, and were more common in deeper synovial tissue. Considerable tissue damage was noted in the vicinity of iron rich siderosomes in synovial A cells from cases of HS, but such deposits in B cells in the synovium from the other cases had relatively little effect. We discuss the possibility that such differences directly reflect the differing functions of type A and B synovial cells, and particularly their relative ability to produce metabolically active oxygen metabolites with tissue destructive potential in the presence of iron.
Liver function was studied in 139 of 291 haemophiliacs known to a single Regional Haemophilia Centre including patients with classical haemophilia, Christmas disease and von Willebrand's disease. In 57 patients, six-monthly liver function tests over a five year period were also available. Thirty-nine of the 139 patients had had jaundice or hepatitis and 56 had a positive test for HBsAb in the blood although few of these had had an identifiable clinical illness. Fifty-eight haemophiliacs had elevated serum aminotransferases at the time of study, but the five year review revealed only six patients who had had persistently abnormal results, although none had clinically evident liver disease. Liver dysfunction was unrelated to a history of hepatitis, to a positive HBsAb test, or to age, type of haemophilia, factor level or frequency of factor replacement treatment. Abnormalities of liver function in haemophilia appear to be unrelated to past or present hepatitis B infection in most cases and may not be related to any single transmitted infectious agent.
HLA typing for antigens of the A, B, C, and DR loci was carried out on lymphocytes from a haemophilic (Type A) family which included four siblings with arthritis. No single haplotype was found to relate to the presence of haemophilia or haemophilic arthritis.
Immune complexes (IC) are frequently found in the venous blood and synovial fluid of patients with rheumatoid arthritis (RA). Although IC are claimed to have a pathogenetic role in RA, there is generally poor correlation between different IC tests and between individual tests and clinical features. We have therefore sought differences in the levels of IC detected by the Clq binding assay (ClqBA) and the indirect polymorphonuclear phagocytosis test (IPPT) in the arterial and venous blood of 16 patients with RA and 6 disease control subjects to determine which IC are pathogenetically important. Complement components, IgA, IgG, and rheumatoid factor were also measured. Eight of 10 patients with clinically active RA had higher ClqBA results in arterial blood while IgA IC in the IPPT and most complement components were higher in venous blood. No such differences were seen in patients with inactive RA or controls. These results suggest that IC other than those containing IgA are not formed in limb tissues including the synovium and may explain the variable results previously seen in patients with RA.
A detailed clinical and radiological examination of the joints and laboratory studies were carried out on 139 haemophiliacs attending a single centre. The group included more patients with mild and moderate haemophilia (factor levels 6 to 60 per cent) than in previous studies. Haemarthrosis, the most common bleeding manifestation, had affected more than two-thirds of patients including many with mild or moderate disease. Restriction and contracture of the knees and elbows were the most common clinical features and, with the ankles, these joints were most frequently affected both clinically and radiologically. Using a combination of clinical and radiological features, 42 per cent of the patients could be classed as having 'definite' and a further 14 per cent 'possible' haemophilic arthritis. Although haemarthroses were equally prevalent in patients with classical haemophilia and Christmas disease, arthritis was more frequently present in the former. Haemarthrosis and joint disease were exceptional in von Willebrand's disease. The prevalence of arthritis generally related to disease severity as measured by factor level but, in contrast to earlier studies, definite arthritis was seen in some patients with factor levels up to 20 per cent of normal although the number of affected joints was less in these patients with milder disease. Laboratory test abnormalities including circulating immune complexes and hypocomplementaemia were noted in some patients but the abnormalities correlated poorly with clinical features. The present results suggest a recent slight reduction in the prevalence or severity of haemophilic arthritis, possibly attributable to recent improvements in factor replacement treatment. Longer-term studies are required to show whether arthritis is indeed lessening or whether the onset is merely being delayed.
The prevalence of radiological abnormalities of the sacroiliac joints, the manubriosternal joint, and the lumbar spine were assessed, and quantitative sacroiliac scintigraphy was performed in 151 patients with a history of chronic inflammatory back pain and in 31 controls with non-inflammatory back pain. Sacroiliitis was found in 124 patients (82%), manubriosternal lesions in 84 patients (56%), and lesions of the lumbar spine in 58 patients (38%). In 19 patients (13%), manubriosternal lesions provided the sole radiological abnormality and in five patients (3%) no radiological abnormality could be demonstrated at any of these sites. Quantitative sacroiliac scintigraphy showed increased values in 69 of 137 patients examined (50%), but also in 10 out of 12 control patients with disc degeneration (83%) and is, therefore, nonspecific for inflammatory lesions. Radiological examination of the manubriosternal joint is recommended in patients with inflammatory back pain without radiographic evidence of sacroiliitis.
The modified New York criteria for the diagnosis of ankylosing spondylitis were evaluated and compared to the older criteria in 151 patients, referred to hospital because of low back pain and who had a positive clinical history screening test for ankylosing spondylitis and in 31 controls with non-inflammatory back pain. Radiological examination of the sacro-iliac joints showed sacro-iliitis in 124 (82%) from the 151 with inflammatory back pain. In 110 (72%) of those patients a diagnosis of definite ankylosing spondylitis according to the classical New York criteria could be made and they had a prevalence of HLA-B27 of 84%. Application of the modified New York scheme increased the number of patients meeting the criteria for definite ankylosing spondylitis to all 124 patients with sacro-iliitis, and 82% of this group carried HLA-B27. The classical New York criteria of 'limitation of the lumbar spine in three directions' and of 'limitation of chest expansion' appeared to reflect disease duration rather than help in the initial diagnosis.
The majority of severe haemophiliacs will develop a crippling arthritis consequent upon recurrent haemarthroses although the pathogenic mechanism remains unclear. We have carried out technetium-99 pertechnetate joint scans in the elbows, knees and ankles of 23 haemophilic patients and compared the isotope uptake of the 15 patients with clinical and radiological evidence of arthritis to that of eight patients without arthritis, to 13 age-matched healthy male controls, and to 10 age-matched males with active rheumatoid arthritis. Isotope uptake into the knee joints was significantly higher in haemophilic arthritis than in controls, haemophiliacs without arthritis, and patients with rheumatoid arthritis [median percentage uptake of administered technetium (Tc) dose X 10(3) in right knee = 9.4, 6.2, 6.4 and 6.6, respectively]: and the differences from haemophilic arthritis were all significant (p less than 0.01, Mann-Whitney U test). Similar differences were seen in the elbows and ankles. Increased Tc uptake correlated strongly with frequency of haemarthrosis, pain, synovitis, range of movement and radiological changes in knees and elbows, but poorly with the lesser changes seen in the ankles. These results would support the theory that haemophilic arthritis amongst the inflammatory arthropathies and that scanning is an appropriate technique for following progression of joint disease.
Two cases of alpha-1-antitrypsin associated liver disease occurring in patients with rheumatoid arthritis are described. Both presented with abnormal liver function tests and the true diagnosis was only apparent after liver biopsy and detailed serological studies. The concurrence of these two conditions is noteworthy because of the postulated role of proteolytic enzymes in producing the characteristic cartilaginous erosions of rheumatoid arthritis.
Non-steroidal anti-inflammatory drugs are theoretically contra-indicated in the haemophilias but might be useful for those patients with chronic arthritic pain, as long-term strong analgesics are also undesirable. We carried out studies of platelet function and coagulation in 8 normal controls and 7 haemophiliacs while they were taking sequentially benoxaprofen and salsalate. No significant alterations in platelet function, bleeding time or coagulation occurred with either drug. In a subsequent double-blind controlled clinical trial using ibuprofen and placebo 8 of 9 patients had a significant reduction in pain score whilst using ibuprofen without significant change in the frequency of bleeds or the amount of concentrate used. Laboratory measures of coagulation also failed to reveal any adverse effect of the active drug. Non-steroidal anti-inflammatory drugs may be beneficial and may be used with caution in haemophilia.
A double blind placebo controlled trial was carried out over a 6-month period on 17 patients with ankylosing spondylitis (AS) to assess the effect of the second line antirheumatic drug, D-penicillamine. The patients included 13 with peripheral joint involvement. No significant improvement over placebo was detected in a variety of clinical and laboratory indices in the patients receiving active treatment. This controlled trial would not support a use for penicillamine in AS.
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Using a computerized electron-probe X-ray microanalytical technique to measure phosphorus/iron ratios we have defined the iron saturation of ferritin in vitro from prepared ferritin standards of known iron loading. This technique has been applied to the study of 5 haemophilic synovial membranes. At light microscope level the distribution and relationship of iron/ferritin were defined using Perls' reaction and an immunoperoxidase technique respectively. The synovia from all cases contained intra and extra-cellular deposits of Perls' positive material which were granular in nature in the most superficial synovial cells. There were increasing numbers of pheomorphic (1-12 micron diameter ovate bodies in the deeper synovial layers. Immunoperoxidase ferritin staining produced a strongly positive reaction in the granular material but the ovate bodies were negative with the exception of some peripheral staining. X-ray microanalysis showed the granular material to be highly iron saturated ferritin and the ovate bodies to be almost pure iron. We suggest that iron saturated ferritin in the synovial membrane could increase/perpetuate inflammation by promoting lipid peroxidation.