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Biomedical subjects

O L Meyers

Publications and source records attributed to O L Meyers.

At least 19 recordsLinked to original sources
PubMed1995

Prostanoid modulation of synovial antigen-specific CD4+ T-cell cytotoxic function in rheumatoid arthritis.

The recent demonstration of cytolytic mediators within synovial CD4+ T-cells of patients with rheumatoid arthritis (RA) has suggested an additional role for these cells in the pathogenesis of the disease. In this study we have investigated the function and regulation of antigen-specific class II-restricted cytotoxic T-cells from the synovial fluid (SFMNC) and peripheral blood (PBMNC) of 20 seropositive RA patients, and correlated in vitro findings with clinical data. Regulatory factors including prostaglandin E2 (PGE2), interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) were measured in cell supernatants. A diversity in SFMNC antigen-specific cytotoxicity that correlated with therapy and PGE2 production was found, and shown to be mediated by synovial prostanoid (products of cyclooxygenase metabolism) inhibition of effector function. Our findings indicate that SFMNC cytotoxicity may be important in the pathogenesis and treatment of RA. Cyclooxygenase inhibition as the sole treatment early in RA may reduce the potentially beneficial inhibitory effect of synovial prostanoids on antigen-specific SFMNC cytotoxicity.

Adult↗
PubMed1995

Responsiveness of Keitel functional index compared with laboratory measures of disease activity in rheumatoid arthritis.

This study compares functional changes to change in measures of disease activity following the introduction of slow-acting anti-rheumatic drugs (SAARD) in patients with active rheumatoid arthritis (RA). Clinical and laboratory variables were simultaneously monitored at 6-monthly intervals, over approximately 18 months. Function was measured by a performance testing, the Keitel function index (KFI), which was divided into sections representing small and large joints [hand (HFI); wrist (WFI) and limb function index (LFI)]. One-hundred-and-fifteen patients were studied, of whom 21 were male. The mean age of the subjects was 49 yr (S.D. +/- 12) and mean duration of disease 7 yr (S.D. +/- 7). The mean KFI at entry was 38 (S.D. +/- 18) while at the end of the study it was 31 (S.D. +/- 17) (P < 0.0001). The change in KFI following therapy correlated with the change in Ritchie articular index (RAI) (r = 0.4; P < 0.0001), early morning stiffness (EMS) (r = 0.3; P = 0.004), swollen joint count (JC) (r = 0.4; P = 0.0005), C-reactive protein (CRP) (r = 0.2; P < 0.05) and Lansbury systemic index (LSI) (r = 0.35; P = 0.002), but not with change in Westergren erythrocyte sedimentation rate (ESR) or change in time to onset of fatigue. Multiple regression analysis showed that 32% of the variation in KFI at the end of the study could be predicted by a combination of ESR, sulphasalazine therapy, RAI, disease duration and chloroquine treatment at onset (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Inflammatory Agents↗
PubMed1994

A risk-benefit assessment of slow-acting antirheumatic drugs in rheumatoid arthritis.

There is no ideal slow-acting antirheumatic drug. Therapy of rheumatoid arthritis (RA) is currently being modified, with strong recommendations to abandon the traditional pyramidal approach. The call is for a more aggressive, earlier approach to suppress inflammation. Combination therapy rather than the use of a single agent is advocated by some. Improved methods for assessing disease activity as well as measurement of outcome have been developed. Markers of poor prognosis have helped to define patients for earlier treatment. Comparison of toxicity among such a diverse group of drugs is probably best achieved with a toxicity index measuring the number of episodes expressed in terms of patient-years of exposure. Toxicity remains the commonest reason for discontinuing an agent, while remission beyond 36 months on therapy is uncommon, except with methotrexate. The profile of toxicity is clearly defined for individual agents, but combination therapy may reveal an entirely different set of toxic manifestations. There is an urgent need to develop a set of risk factors to predict toxicity in an individual patient. Juvenile chronic arthritis behaves differently from adult RA. Drug toxicity profiles are similar, but less common. Outcome is more difficult to measure, with the major impact of disease and therapy being on growth retardation.

Adult↗
PubMed1994

Corticosteroid therapy and bone mass--comparison of rheumatoid arthritis and systemic lupus erythematosus.

This study was designed to evaluate the effects of low-dose corticosteroid (CS) therapy for rheumatoid arthritis (RA) and of high-dose CS therapy for systemic lupus erythematosus (SLE) on metacarpal bone mass in young (premenopausal) subjects. Ninety-eight patients with RA, 63 patients with SLE and 85 healthy controls of comparable age, race, sex and nutritional status were studied. Metacarpal bone mass was measured by radiogrammetry using a digitiser. In the RA patients, mean bone mass of CS-treated subjects (27%) was 52.31 g/cm2, while that of untreated subjects was 56.69 g/cm2 (P < 0.02). In the SLE group, mean bone mass of CS-treated subjects (76%) was 61.47 g/cm2 and that of untreated subjects 62.36 g/cm2 (P > 0.1). Although patients with SLE required larger cumulative doses of CS for longer periods, their bone mass was higher than that of the RA subjects (P < 0.01). None of the patients had femoral neck or vertebral crush fractures. In RA, bone loss was probably a feature of severe disease rather than of CS therapy.

Adrenal Cortex Hormones↗
PubMed1992

Metacarpal bone mass in systemic lupus erythematosus.

We report the prevalence of metacarpal cortical thinning in systemic lupus erythematosus (SLE). Fifty-eight ambulant female patients attending a lupus clinic (mean age 32.4 years), were found to have significant thinning of metacarpal cortices (p < 0.05) when compared with 63 normal females (mean age 34.1 years). However, metacarpal bone mass was within the normal range. Measurements were made at 6 metacarpals of the 2 hands using a computer-aided technique (digitized radiogrammetry). Femoral cortical width and Singh index at the left femur, as well as the vertebral index at L3 were also recorded. The trabecular indices were in the range of normality, but the SLE group had more patients in the immediately pre-osteopenic range. Metacarpal bone loss was not related to disease duration or corticosteroid therapy. The prevalence of osteopenia in SLE is probably underestimated and the pathogenesis is likely to be multifactorial.

Adrenal Cortex Hormones↗
PubMed1992

Nutritional status in rheumatoid arthritis. Effects of disease activity, corticosteroid therapy and functional impairment.

Sixty-five patients with rheumatoid arthritis (RA) (mean age 37.2 years) were compared with 71 controls (mean age 33.8 years). Anthropometric measurements included body diameters and skin-fold thickness at multiple sites, while biochemical markers of nutritional status included serum albumin, thyroxine-binding pre-albumin and retinol-binding globulin levels. None of the RA subjects was outside the range that extended 2 standard deviations above and below the normal control values for lean body mass. Discriminant analysis showed that corticosteroid therapy did not significantly influence skinfold thickness in RA. A combination of bi-acromial and bi-ankle diameters had a sensitivity of 70% and a specificity of 72% in differentiating the RA group, in whom disease activity had a greater effect on body diameters than corticosteroid therapy did. Differences related to functional impairment were a manifestation of disease activity rather than a direct effect on skinfold thickness or body diameters. According to anthropometric measurements in ambulant patients, RA does not result in malnutrition in young individuals.

Adrenal Cortex Hormones↗
PubMed1991

HLA DQ beta restriction fragment length polymorphism and rheumatoid arthritis. Association between DQw7 and rheumatoid arthritis in DR4-positive subjects.

Two variants of the HLA-DR4-linked DQw3 allele, namely DQw7 and DQw8, were analysed in patients of mixed ancestry (Cape Coloureds) with rheumatoid arthritis and in healthy individuals from the same population group using a DQ beta-specific cDNA probe. The DQw7 allele, identified by 3,4 kb Hind III or 3,7 kb and 6,9 kb Bam HI DQ beta-specific restriction fragments, was expressed in 93% of DR4-positive patients (N = 15), compared with 12.5% DR4-positive normal individuals (N = 8). This DQ variant showed a highly significant association (relative risk = 98; P less than 0.0001) with rheumatoid arthritis in this population group and may play a role in their susceptibility to this disease.

Alleles↗
PubMed1991

Prevalence of biochemical and immunological abnormalities in rheumatoid arthritis.

The prevalence of biochemical and immunological abnormalities was studied in a group of 256 patients with rheumatoid arthritis (104 coloureds, 100 whites and 52 blacks). The most common biochemical abnormalities detected were a reduction in the serum creatinine value (43.4%), raised globulins (39.7%), raised serum alkaline phosphatase level (42.3%), reduction in serum albumin value (8.1%), a mild rise in serum creatinine value (6.6%), and a raised serum gamma-glutamyltranspeptidase (GGT) level (6.5%). The prevalence of a rise in the GGT was less frequent than reported in other published studies. The immunological abnormalities noted were a positive rheumatoid factor (78.9%), positive anti-nuclear factor (36%), raised serum IgG (43.3%) and IgA (10.5%) values, positive smooth-muscle antibody (12.5%) and elevated double-stranded anti-DNA antibody levels (2.3%). Inter-group comparisons showed that the serum IgG and IgA and total globulins were significantly higher in blacks and coloureds than whites; these findings may be related to a higher prevalence of malnutrition and infection in childhood in these communities. There were no significant inter-group differences that could be attributed to rheumatoid arthritis.

Adult↗
PubMed1991

Increased metacarpal bone mass following 18 months of slow-acting antirheumatic drugs for rheumatoid arthritis.

Osteoporosis in RA is mediated by numerous inflammatory substances. This study was undertaken to see if SAARD could modify the rate of metacarpal bone loss in RA. Combined cortical thickness (CCT) measured at the midshaft of the right second metacarpal was used to calculate bone mass (CA%) using a digitizer. Eighty-one subjects were studied, all of whom had at least three sets of hand X-rays, the last of which was approximately 18 months following initiation of SAARD therapy. There were 12 males and 69 females. The mean age at time of starting therapy was 51 (SD 12) years while the mean duration of disease at the time was 7.6 (SD 8) years. The mean time to referral for SAARD from the general clinic was 2.5 (SD 3) years. The percentage fall in bone mass prior to therapy was 2.51%/day compared to a gain of 0.6%/day after therapy (P less than 0.05). Forty-nine patients were aged over 50 years while 32 were 50 years or younger at the time of study. Comparison showed that in the pretreatment period, the rate of change in CCT and CA% was not significantly dependent age (P less than 0.1). During that therapy, the rate of change in CCT and CA% significantly different in the two age groups. Patients aged over 50 years continued to lose bone, but at a slower rate (P less than 0.05). Patients aged 50 years or less either stopped losing or gained metacarpal bone mass during the study period (P less than 0.005). The time to referral for SAARD and disease duration (comparable in the two age groups) did not have a significant effect on changes in CA% during therapy. Change in bone mass could be predicted by change in disease activity. We conclude that SAARD have a significant sparing effect on metacarpal osteoporosis in RA. This positive effect is masked by the overwhelming influence of age (and menopause) and could be missed. Metacarpal osteoporosis seems a pathophysiologically more useful measure of radiological change in RA than erosions or joint space narrowing.

Aging↗
PubMed1990

Therapeutic requirements in rheumatoid arthritis.

Therapeutic requirements were determined for a group of 256 patients with rheumatoid arthritis (RA) attending the Rheumatic Diseases Unit in Cape Town. Two-thirds of the patients had received or were receiving physiotherapy and half occupational therapy. Antidepressants had been taken by 24.2%, and 31.3% had received tranquillisers. All the patients had received non-steroidal anti-inflammatory drugs and 84 (32.8%) oral corticosteroids. One hundred and eighty-two patients (71.1%) had received one or more intra-articular or intralesional corticosteroid injections. A remittive agent or immunomodulatory drug had been prescribed to 163 patients (63.7%). Half the patients had undergone one or more surgical procedures for their RA. The outcome of management was favourable in the majority of patients, 78.1% having little or no functional disability. The management of patients with RA requires a team effort involving many different health professionals, and patients often require multiple drugs for the control of their disease.

Adjuvants, Immunologic↗
PubMed1989

Nutritional assessment in rheumatoid arthritis.

The nutritional status was assessed in a group of 220 patients with rheumatoid arthritis from three communities (coloured 89 patients, white 88 and black 43). The triceps skinfold (TSF) thickness, upper arm muscle circumference (UAMC), body mass index (BMI) and percentage of ideal body weight (% IBW) were measured and the serum albumin value determined. The mean age of the coloured patients was 49.8 years, white 57.7 years and black 44.8 years. Forty-five patients (20.5%) had a reduction of one or more anthropometric measurements (TSF, UAMC and/or %IBW) and a further 6 patients (2.7%) had a reduction of the serum albumin value alone. These 51 patients were considered to be malnourished and had a higher mean erythrocyte sedimentation rate and more severe functional disability than the remainder of the patients. The prevalence of malnutrition was lower if diagnosed only on abnormality of the TSF, UAMC and %IBW, since 25 patients (11.4%) had a reduction of only one measurement, 12 (5.5%) had a reduction of 2 and 8 (3.6%) had a reduction of all three measurements. Obesity (BMI greater than 30) was noted in 10.5% and there were no differences in the functional disability, disease activity and use of steroid therapy in the obese patients compared with the rest of the patients.

Adult↗
PubMed1989

Association of rheumatoid arthritis with HLA in three South African populations--whites, blacks and a population of mixed ancestry.

The association between rheumatoid arthritis and HLA was studied in three South African populations: whites (N = 66), blacks (N = 33) and patients of mixed ancestry (Cape Coloureds) (N = 183). The antigens of the HLA-A, B, C, DR and DQ loci were detected by microlymphocytotoxicity assay and their frequencies in the three patient groups were compared with the corresponding frequencies in normal individuals of the same population group. HLA-DR4 was significantly associated with rheumatoid arthritis in whites (P less than 0.0001), blacks (P less than 0.001) and patients of mixed ancestry (P less than 10(-6]. The relative risk for HLA-DR4 was 3,2 in whites, 3,9 in blacks and 3,7 in patients of mixed ancestry. Other significant associations detected were with HLA-A2 in whites and HLA-B8 and DQw3 in patients of mixed ancestry. The constant association with HLA-DR4 seen in the different populations provides support for the suggestion that the HLA genes themselves are responsible for the genetic susceptibility to rheumatoid arthritis.

Arthritis, Rheumatoid↗
PubMed1989

Osteoporosis screening--radiogrammetry revisited.

Radiogrammetry remains a convenient method of bone mass measurement. It is the only objective means of quantifying metacarpal osteoporosis (OP) in rheumatoid arthritis (RA). An automated technique using a digitizer (interfaced with an IBM PC) for measurement of combined cortical width (CCW) at the mid-shaft of six metacarpals was evaluated in three groups of individuals under 50 years of age (98 normal controls, 96 RA, 63 SLE). Intra-observer, inter-observer, and inter-institution reproducibility was assessed with a 'phantom' embedded in a rectangular mould of wax. Intra-patient variation was also assessed in RA patients seen on two occasions less than a month apart. Two hundred and fifty-seven subjects were studied. The method was found to be reproducible for a single observer, among five different observers and in two separate institutions. The RA subjects seen on two occasions showed no significant differences in CCW. The technique showed significant differences of CCW in the three groups of premenopausal subjects (controls; RA; SLE) studied (p less than 0.001). The six metacarpal bone mass was calculated in less than 5 min. The technique of digitized radiogrammetry is an improvement on the Vernier caliper technique. The method is useful for epidemiological cross-sectional studies and for evaluation of long-term radiological changes in RA.

Adult↗
PubMed1989

Rheumatoid arthritis in blacks in South Africa.

The spectrum of rheumatoid arthritis (RA) was studied in a group of 52 blacks who attended a rheumatology unit in Cape Town, South Africa. The mean age of the patients was 44.6 years, and the female to male ratio was 3.7:1. Significant radiographic changes were frequently noted, and the mean Larsen scores were 34.9 for the hands, 19.6 for the feet, and 6.6 for the wrists. About two thirds of the patients had received an immunomodulatory drug and 20 (38%) had had one or more surgical procedures for their RA. Anaemia was the commonest extra-articular manifestation, and although the other extra-articular features were uncommon, a variety of features had been detected during the course of the disease. Earlier studies on blacks in Africa suggested that RA was a mild disease; our findings, however, are in agreement with the more recent surveys, which suggest that severe disease is not uncommon.

Adolescent↗