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M I Cawley

Publications and source records attributed to M I Cawley.

At least 19 recordsLinked to original sources
PubMed1999

The prevention of corticosteroid-induced bone loss with intermittent cyclical etidronate.

A prospective, randomised, double-blind, placebo controlled primary prevention trial was undertaken in 28 patients commencing low to moderate doses of corticosteroids for the first time. Patients were randomised to intermittent cyclical etidronate (400 mg daily for 2 weeks) and calcium (500 mg daily for 11 weeks) or intermittent cyclical placebo with calcium. After 52 weeks of treatment, lumbar spine BMD increased by 1.8% in the etidronate group, while it decreased by 3.7% in the placebo group. The differences in bone loss rate were statistically significant (p<0.01) at both 6 and 12 months. Similar trends were observed at the proximal femur, but differences were not statistically significant. These results suggest that intermittent cyclical etidronate therapy is effective in the primary prevention of corticosteroid-induced bone loss at the lumbar spine.

Absorptiometry, Photon↗
PubMed1998

Safety and tolerability of conversion from stable Sandimmun maintenance treatment to Sandimmun Neoral in patients with rheumatoid arthritis.

OBJECTIVE: To assess the safety and tolerability of converting patients with rheumatoid arthritis (RA) taking a stable dose of cyclosporin A (CyA) maintenance treatment (Sandimmun, SIM) to a new microemulsion capsule formulation, Sandimmun Neoral (Neoral), at an initial dose of 2.5 mg/kg/day. METHODS: In this single arm, open multicenter study, 28 patients were recruited to enter a 6 week pre-conversion period; of these, 22 patients completed 12 weeks' treatment with Neoral. RESULTS: During the 12 week post-conversion period, 11 patients experienced adverse events considered to be drug related; most were mild to moderate in severity and reflected the known safety profile for CyA. Only slight differences in efficacy variables were observed after conversion. The mean Neoral dose at Week 12 (2.84 mg/kg/day) was lower than the mean SIM pre-conversion dose (3.38 mg/kg/day). The study showed that, in patients with RA undergoing stable SIM maintenance treatment, conversion to an initial Neoral dose of 2.5 mg/kg/day did not give rise to any clinically relevant safety and tolerability concerns, and efficacy of the treatment was maintained compared with SIM. CONCLUSION: This conversion strategy constitutes a clinically acceptable alternative to a 1:1 dose conversion.

Adult↗
PubMed1997

Binucleated and multinucleated forms of plasma cells in synovia from patients with rheumatoid arthritis.

A morphological examination of synovial tissue from 25 patients with rheumatoid arthritis revealed that binucleated or multinucleated plasma cells were present in all samples and absent in synovia obtained from 16 control patients. Plasma cells containing two, three of four nuclei constitute a mean 3% of the total plasma cell population. They were always found amongst plasma cell infiltrates and in close association with small blood vessels. Ultrastructural analysis found no evidence of cellular membranes separating the individual nuclei in binucleated or multinucleated plasma cells, suggesting that the cells did not arise from fusion. Some of these plasma cells had a diameter approaching 100 microns, and many were in intimate contact with macrophages. The demonstration of a few cells with mitotic figures within the infiltrates suggests that the maintenance of plasma cell numbers in rheumatoid synovium may depend, in part, upon their local proliferation.

Aged↗
PubMed1997

Mast cell activation in arthritis: detection of alpha- and beta-tryptase, histamine and eosinophil cationic protein in synovial fluid.

1. Although mast cell hyperplasia is a feature of rheumatoid arthritis and osteoarthritis, the extent and nature of mast cell activation in joint disease have not been clearly established. 2. We have investigated the levels of mast cell tryptase and histamine and also of eosinophil cationic protein in synovial fluid collected from 31 patients with rheumatoid arthritis, 14 with seronegative spondyloarthritis and nine with osteoarthritis. Two RIAs for tryptase were employed: one with monoclonal antibody AA5, which was found to bind equally well to both alpha and beta isoforms on Western blots of the recombinant enzyme, and the other with antibody G5, which recognizes predominantly beta-tryptase. 3. alpha-Tryptase, which is likely to be released constitutively from mast cells, appeared to be the major form in synovial fluid, as the assay with antibody AA5 detected appreciably more tryptase than that with antibody G5. beta-Tryptase, which is released on anaphylactic activation of mast cells, was detected in 14 out of 45 synovial fluid samples studied, with concentrations of up to 12 micrograms/l measured by the G5 assay. The apparent levels of beta-tryptase, but not of alpha-tryptase, were closely correlated with those of histamine in the synovial fluid. Patients with osteoarthritis appeared to have a greater proportion of beta-tryptase in the synovial fluid than those with rheumatoid arthritis, as well as higher concentrations of histamine. Eosinophil cationic protein was present at high levels in the synovial fluid, although eosinophil numbers were low, and its concentrations were not correlated with the concentrations of the mast cell products. 4. These data suggest that anaphylactic degranulation of mast cells may have occurred to a greater extent in osteoarthritis than in rheumatoid arthritis, despite the relative lack of synovial inflammation in osteoarthritis. Although the eosinophil cationic protein detected may not reflect eosinophilic inflammation in the joint, the presence in synovial fluid of tryptase of both major forms, and of histamine, appears to indicate that mast cell products are secreted constitutively, as well as by processes of anaphylactic degranulation in rheumatoid arthritis, seronegative spondyloarthritis and osteoarthritis.

Adult↗
PubMed1997

Chrysiasis.

Explore the source record for details and available documents.

Antirheumatic Agents↗
PubMed1996

Lateral bone density measurements in osteoarthritis of the lumbar spine.

OBJECTIVE: To investigate whether spinal osteoarthritis (OA) is responsible for the common finding that lumbar spine bone mineral density (BMD) is greater when measured in the anteroposterior plane than when measured in the lateral plane. METHODS: We studied lateral spine radiographs from 63 women who attended a hospital outpatient department for bone density measurement and who also underwent lumbar spine radiography. Osteoarthritis was assessed using both the Kellgren and Lawrence scale and a scoring system for osteophytosis. Bone density was measured in the anteroposterior and lateral planes using a Hologic QDR-2000 instrument. RESULTS: The mean anteroposterior BMD (0.92 g/cm2) was significantly greater than the lateral BMD (0.59 g/cm2) (p < 0.01), and the difference between antero-posterior and lateral measurements was significantly associated with both increasing Kellgren and Lawrence score and osteophyte score, even after adjustment for age. CONCLUSION: These data suggest that spinal OA is a major cause of the difference between anteroposterior and lateral BMD and that lateral BMD may provide a more accurate representation of true vertebral body bone density in patients with OA of the lumbar spine.

Absorptiometry, Photon↗
PubMed1996

Reference ranges of bone mineral density for women in southern England: the impact of local data on the diagnosis of osteoporosis.

The construction of reference ranges that accurately represent the population at large is essential for the correct identification of osteoporosis from bone mineral density (BMD) measurements. In this study, reference data supplied by the manufacturer of the Lunar DPX+ bone densitometer were compared with data obtained locally. Lumbar spine, proximal femur and total body BMD measurements were made in an age-stratified random sample of 702 Southampton women aged 20 to 89 years. Relevant demographic and medical data were recorded for each subject using a questionnaire. Reference curves of BMD (mean +/- SD) were plotted against age for each measurement site and were found to be higher than the manufacturer's reference values at all ages and sites. Exclusion of women with factors known to affect bone mass only served to increase this discrepancy. According to World Health Organisation definitions, osteoporosis may be identified from BMD values alone. Based upon neck of femur BMD values, 100 (14.8%) of the women in this study group were categorized as osteoporotic using local young normal reference data, compared with only 39 (5.8%) using the manufacturer's data. By normalizing for age distribution, these findings were extrapolated to the local population where it was predicted that 26.0% and 10.1% of females over 50 years of age would be classified as osteoporotic using the respective reference ranges. This study clearly illustrates how the numbers of women diagnosed as osteoporotic vary with the use of different reference populations.

Adult↗
PubMed1996

Interleukin-2 is found in the synovium of psoriatic arthritis and spondyloarthritis, not in rheumatoid arthritis.

Objective of this project was to determine whether synovial expression of interleukin-2 (IL-2) in arthritis is a disease-specific phenomenon. Immunohistological examination of needle biopsies from 7 rheumatoid arthritis (RA) patients never exposed to disease modifying antirheumatic drugs (DMARDs), 13 RA patients on DMARDs, 4 patients with seronegative spondyloarthritis (SpA), and 5 psoriatic arthritis (PsA) patients. Biopsies were either snap-frozen immediately or cultured for 48 hr, with and without phytohaemagglutinin (PHA) prior to APAAP staining. In snap-frozen biopsies, IL-2 was detected in none of 18 RA samples with significant T cell infiltrates. In contrast, IL-2 was seen in 7/9 PsA/SpA samples. After culture without PHA, IL-2 was detected in 0/14 RA and 5/6 PsA/SpA samples; with PHA, IL-2 was present in 1/14 RA and 2/2 PsA/SPA samples. Synovial IL-2 protein expression appears to distinguish between RA (absent) and PsA/SpA (present). This may reflect a difference in pathophysiology between these diseases.

Adolescent↗
PubMed1995

Chrysiasis revisited: a clinical and pathological study.

Chrysiasis is a distinctive and permanent pigmentation of light-exposed skin resulting from the administration of parenteral gold salts. We report a study of 40 Caucasian patients with rheumatoid arthritis, treated with intramuscular sodium aurothiomalate, of whom 31 had chrysiasis. Visible changes develop above a threshold, equivalent to 20 mg/kg gold content, and their severity depends upon cumulative dose. Focal aggregates of particulate gold are deposited in the reticular and papillary dermis in amounts that correlate with the degree of pigmentation. Characteristically, initially the periorbital region is affected by a mauve discoloration, which intensifies and deepens into a blue/slate-grey colour, while extending to involve the face, neck and upper limbs. Although chrysiasis develops insidiously and patients may be unaware of the changes, positive identification is important in order to avoid misdiagnosis and medical mismanagement, and afford appropriate reassurance. Prevention is difficult, but measures to reduce sunlight exposure may be helpful.

Antirheumatic Agents↗
PubMed1995

Familial aggregation of undifferentiated spondyloarthropathy associated with HLA-B7.

OBJECTIVE: To report multiple cases of recurrent seronegative arthropathy, enthesopathy, or both, occurring in a single family in the absence of the HLA-B27 tissue type, coexistent psoriasis or inflammatory bowel disease. METHODS: Three generations of one family together with their general practitioners completed a standard questionnaire. All subjects with a positive questionnaire and two randomly chosen subjects with negative questionnaires were then examined by a single observer. HLA tissue typing and standard sacroiliac radiographs were performed. RESULTS: Seven of 12 family members with a positive questionnaire had early onset oligo- or polyarthritis, enthesitis, or both, and fulfilled established criteria for spondyloarthropathy, although none had radiological evidence of sacroiliitis. The mean age at first symptom in this group was 22 years with only one individual having the first symptom over the age of 30 years. All subjects were rheumatoid factor negative. Histocompatibility studies showed a strong association with the HLA-B7 antigen. CONCLUSIONS: The observations provide further support for the existence of 'undifferentiated' spondyloarthropathy and suggest that this can be associated with genetic factors other than HLA-B27.

Adolescent↗
PubMed1995

Osteoarthritis of the hip joint and acetabular dysplasia in women.

OBJECTIVE: To investigate the suggestion that osteoarthritis (OA) of the hip joint is often caused by subclinical acetabular dysplasia among elderly British women. METHODS: We examined 393 hip joints from the radiographs of a sample of women aged 60-75 years undergoing intravenous urography. Acetabular dysplasia was assessed using measurements of the centre-edge (CE) angle and acetabular depth (AD), which are both reduced in this condition. OA was assessed using an overall grade based on the Kellgren and Lawrence system and by measurement of minimum joint space (MJS). RESULTS: MJS was the more repeatable measure of OA, and showed a strong correlation with overall grade (Spearman rank correlation coefficient rs = -0.61, p < 0.01). MJS was significantly negatively correlated with CE angle (Pearson correlation coefficient r = -0.25, p < 0.001) and AD (r = -0.11, p < 0.05). Consistent with these findings, there was a weak but significant positive correlation between overall grade of OA and one of the two measures (CE angle) of acetabular dysplasia. CONCLUSIONS: These results do not support the hypothesis that mild degrees of acetabular dysplasia account for a substantial proportion of hip OA in elderly women. Changes in hip joint geometry as a result of OA may be responsible for the weak negative association observed.

Aged↗
PubMed1994

Detection of T-cell receptor beta chain mRNA in frozen and paraffin-embedded biopsy tissue using digoxigenin-labelled oligonucleotide probes in situ.

In situ hybridization techniques using a cocktail of digoxigenin-labelled T-cell receptor (TcR) constant (C) region beta oligonucleotide probes were used to detect TcR beta mRNA in frozen and paraffin-embedded tissue sections. The specificity of the C beta cocktail was confirmed by Northern blot analysis. The TcR C beta cocktail successfully hybridized to T cells in frozen and paraffin-embedded tissue obtained from patients with inflammatory arthropathies, B- and T-cell non-Hodgkin's lymphoma (NHL), and reactive tonsillitis, and showed staining patterns comparable to those obtained by conventional immunohistological detection of T cells. This is the first report of in situ studies using labelled TcR C beta oligonucleotide probes and may indicate the feasibility of investigating clonal T-cell populations using digoxigenin-labelled clonospecific probes in clinical samples in situ.

Biopsy↗
PubMed1994

Abnormal microvascular responses in a lateral epicondylitis.

The laser Doppler flowmeter, an instrument highly sensitive to changes in blood flow velocity in the dermal microvascular bed, was used to examine a sympathetic vasomotor response (SVR) in 40 patients with lateral epicondylitis. There was a significant association between the absence of a normal SVR in the skin overlying the affected enthesis compared with the unaffected contralateral epicondyle (P < 0.01). These results suggest that local dysfunction of the sympathetic nervous system may be associated with the pathogenesis of anatomically discrete pain in the enthesopathy of epicondylitis.

Adult↗
PubMed1994

Cerebellum and brainstem vasculopathy in systemic lupus erythematosus: two clinico-pathological cases.

The case histories are reported of two patients with systemic lupus erythematosus (SLE) who developed fatal neurological involvement, each presenting with cerebellar and brainstem signs. Neuro-pathological changes were confined to the cerebellum and brainstem, with clear evidence of a small vessel vasculopathy. The predominant histological abnormalities were multiple perivascular haemorrhages in one case and classical vasculitic changes in the other.

Adult↗
PubMed1993

Features of systemic sclerosis (scleroderma) in an identical twin pair.

The aetiology of systemic sclerosis (scleroderma) is unknown but it is thought to have both genetic and environmental components. The familial incidence of the disease is very low and we have been able to find only one report of scleroderma in identical twins which was in the Russian literature. We report here on a set of identical twins and their mother who all had features of systemic sclerosis.

Adolescent↗
PubMed1993

Infantile myofibromatosis: a cause of severe bone pain in a neonate.

A 3-week-old, female infant, developed severe bilateral shoulder pain in association with large, symmetrical, lytic lesions in the proximal humeri. The radiological appearance was suggestive of infantile myofibromatosis and bone biopsy confirmed the diagnosis. She subsequently made a complete recovery. This uncommon condition is infrequently confined to bone and except in the presence of obvious pathological fracture, severe pain has not previously been reported.

Bone Neoplasms↗