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Biomedical subjects

G Nuki

Publications and source records attributed to G Nuki.

At least 91 records · Page 5Linked to original sources

Monocyte superoxide anion production in rheumatoid arthritis: preliminary evidence for enhanced rates of superoxide anion production by monocytes from patients receiving penicillamine, sodium aurothiomalate and corticosteroids.

In-vitro studies of superoxide (O-2) anion production by blood monocytes after stimulation with either serum treated zymosan (STZ), IgG treated zymosan (IgGTZ), or fluoride ion (F-) were performed on cells from normal controls (n = 22) and patients with classical or definite rheumatoid arthritis (RA) (n = 35). Twenty-two of the patients were on nonsteroidal anti-inflammatory drugs (NSAID) alone and 13 were on either sodium aurothiomalate, penicillamine, corticosteroids, or a combination. Monocytes from RA patients on 'second-line therapy' showed significantly increased rates of O-2 release in response to STZ compared with normal controls, but no increase was seen in monocytes from patients on NSAID alone. With IgGTZ as the stimulus, rates of O-2 release were increased in monocytes from patients on NSAID alone compared with normal controls (p less than 0.02), but were increased to a greater extent in monocytes from patients on second-line therapy (p less than 0.01). There were no differences in basal unstimulated O-2 production and no differences after stimulation with F-. The enhanced release of O-2 by monocytes from patients on second-line therapy could not be attributed to increased disease activity and may be an effect of therapy.

Adrenal Cortex Hormones↗

Quantitative sacroiliac scintiscanning: a sensitive and objective method for assessing efficacy of nonsteroidal, anti-inflammatory drugs in patients with sacroiliitis.

Serial computer assisted quantitative sacroiliac scintiscanning (SI joint/sacrum ratios) 3 hours after low dosage (5 mCi) 99mTc methylene diphosphonate has been used as an objective index of sacroiliitis in a single blind 14-day cross-over comparison of azapropazone 600 mg b.d. and naproxen 500 mg b.d. in 18 patients with active sacroiliitis. Clinical assessments included visual analogue scales for measurement of pain and early morning stiffness, chest expansion, a modified Schober test, and goniometric measurement of thoracolumbar spinal flexion by means of an inclinometer. Statistically significant decreases in pain (p less than 0.001) and early morning stiffness (p less than 0.001) followed treatment with each NSAID, but there was no significant difference in the fall in these parameters, although 15 out of 18 patients expressed a preference for naproxen. Chest expansion and thoracolumbar flexion were not significantly affected by either drug. Serial quantitative scintigraphy showed a mean fall in joint sacrum ratios following each treatment which was statistically significant (p less than 0.02) only after naproxen. Serial quantitative scintigraphy can be used as an objective method of assessing sacroiliitis and was sufficiently sensitive to reflect the patients' subjective preference in a short-term comparison of 2 NSAID.

Adult↗

Bone mass in nodal primary generalised osteoarthrosis.

Previous studies of patients with primary osteoarthrosis of the hip have suggested an increase in bone mass compared with control populations. Nodal primary generalised osteoarthrosis is known to have a strong familial tendency. To test the hypothesis that this tendency might also lead to increased bone mass, total body calcium has been measured by in-vivo neutron activation analysis and cortical area calculated from measurements of metacarpal indices in 15 female patients with primary generalised osteoarthrosis. The results have been compared with those from 12 healthy controls matched for age, menopausal status, and skeletal size. No significant differences were noted in the total body calcium or cortical area measurements between the 2 groups either before or after correction for skeletal size and menopausal status. No relationship was found between the grade of radiological osteoarthrosis in the hand and either bone mass parameter. Bone mass would not appear to be an important factor in the aetiopathogenesis of nodal primary generalised osteoarthrosis.

Bone Diseases↗

Evidence for intrinsic cellular defects of 'complement' receptor-mediated phagocytosis in patients with systemic lupus erythematosus (SLE).

Fc and 'complement'-mediated phagocytosis of pre-opsonized yeast has been studied in monocytes from 18 patients with SLE. Monocytes from nine of 18 patients had depressed complement-mediated phagocytosis (P = 0.0001, Fishers exact test) but only three of 18 had depressed Fc-mediated phagocytosis (NS, Fishers exact test). Although reduced complement-mediated phagocytosis was correlated with increased frequency of disease manifestations (P less than 0.003, rank correlation) there was no correlation with serum DNA or C1q binding activity, C3 or C4 levels. Serum from SLE patients with depressed phagocytosis did not inhibit phagocytosis by normal monocytes. The data suggests the presence of intrinsic abnormalities of monocyte receptor function in SLE and the nature of the 'complement' receptors involved is discussed.

Adult↗

Functional defects of monocyte C3b receptor-mediated phagocytosis in rheumatoid arthritis (RA): evidence for an association with the appearance of a circulating population of non-specific esterase-negative mononuclear phagocytes.

We have previously described a selective defect of monocyte C3b receptor-mediated phagocytosis in patients with rheumatoid cutaneous vasculitis. We have studied a further 15 rheumatoid arthritis patients with other associated diseases and complications and have identified 4 further patients with a similar defect. Serological and cytochemical studies suggest that the defect in phagocytosis is due to the appearance of increased numbers of large nonspecific esterase-negative mononuclear phagocytes with defective C3b receptor phagocytic function rather than to receptor blockade by immune complexes.

Adult↗

HLA-A, B and DR antigens and properdin factor B allotypes in Caplan's syndrome.

Seventy-nine cases of Caplan's lung were typed for HLA-A and B antigens. The antigen Bw45 was present only in those patients with rheumatoid factor and was of significantly higher frequency (13.6%) when compared to a non-coal dust exposed population of 316 (1.0%). Those patients without rheumatoid factor showed an increase in HLA-A1 and B8 (58.6% and 51.7% respectively) when compared to the rheumatoid factor positive group (29.6% and 25.0% respectively). Clinical and radiological reassessment were performed on 49 of these patients who were also typed for HLA-DR antigens and properdin factor B allotypes. HLA-DR4 was raised in the rheumatoid factor positive group with rheumatoid arthritis (55.2% compared to 25.8% in the non-coal dust exposed group and 37.3% in coalworkers with normal radiographs). The HLA-DR results are comparable to those found in other studies of rheumatoid arthritis not associated with pneumoconiosis. The findings for HLA-A1, B8 and DR4, however, were not significant after correction was made for the number of antigens tested for. No particular Bf allotype was found to be associated with either the lung change or the arthritis. The induction of the pulmonary lesion in Caplan's syndrome is discussed in relation to the HLA findings.

Aged↗

Preliminary studies with azapropazone in gout and hyperuricaemia.

Eight patients with acute gouty arthritis were treated with high dose oral azapropazone 600 mg qds in an open study in order to evaluate its therapeutic potential in acute gout. The drug appeared to be as effective as previous agents used in the management of individual patient's acute gout with resolution of pain in 2-21 days, and it had a potent hypouricaemic and uricosuric effect. The uricosuric effect of azapropazone 300 mg qds and phenylbutazone 100 mg tds was compared in a seven day cross-over study in seven asymptomatic patients with gout and hyperuricaemia. Azapropazone had a more rapid uricosuric effect than phenylbutazone. There was a statistically significant fall in serum uric acid and rise in uric acid clearance 24 hours after starting azapropazone and 72 hours following phenylbutazone.

Adult↗

Total body calcium in rheumatoid arthritis: effects of disease activity and corticosteroid treatment.

Rheumatoid arthritis may be associated with generalised as well as periarticular osteoporosis. To assess the extent of bone loss and the influence of corticosteroid treatment total body calcium was measured by in-vivo neutron activation analysis in 63 patients with rheumatoid arthritis treated with non-steroidal anti-inflammatory drugs alone and 31 treated with additional low-dose corticosteroids. The results were compared with those in 40 normal controls matched for age, sex, and menopausal state. There were significant reductions in mean total body calcium in the group treated with non-steroidal anti-inflammatory drugs (5.3% in men; 6.8% in women) and greater reductions in the corticosteroid-treated patients (11.5% in men, 15.5% in women). The reduction was correlated with disease duration and activity in the patients treated with non-steroid anti-inflammatory drugs alone. Measured total body calcium was significantly less than the values predicted when this relation was used in the corticosteroid-treated patients. The data suggest that increased bone loss in patients with rheumatoid arthritis treated with corticosteroids is attributable to drug treatment rather than disease activity. Many patients with rheumatoid arthritis treated with low-dosage corticosteroids and some postmenopausal women with the disease are likely to be at risk from the complications of osteoporosis.

Adult↗

Hypoxanthine-guanine phosphoribosyl transferase: assay using high performance liquid chromatography.

A method is described for the estimation of hypoxanthine-guanine phosphoribosyltransferase using high performance liquid chromatography. The inosine monophosphate (IMP) generated from hypoxanthine is determined, after separation on a C18 reversed phase silica column with a buffer-methanol gradient, by the absorbance at 254 nm. Simultaneous reciprocal measurement of hypoxanthine consumption is made. The assay is suitable for screening red cell lysates for hypoxanthine-guanine phosphoribosyltransferase deficiency; the results being expressed as nmol inosine monophosphate . h-1. mg-1 haemoglobin. The normal range found was 94 +/- 15 nmol IMP . h-1 . mg-1 haemoglobin and hypoxanthine-guanine phosphoribosyltransferase activities down to 1% of normal can be assayed accurately.

Chromatography, High Pressure Liquid↗

Evidence for defect of complement-mediated phagocytosis by monocytes from patients with rheumatoid arthritis and cutaneous vasculitis.

In-vitro measurements of the rate of monocyte phagocytosis of heat-killed yeast preopsonised in human AB serum from 14 patients with rheumatoid arthritis and 14 normal controls showed a significant reduction in five patients with active vasculitis but no change in nine with active arthritis alone. Further studies of complement- and Fc-mediated monocyte phagocytosis in which the rate constants (Kc and KFc respectively) were determined using complement-coated Saccharomyces cerevisiae and Candida albicans opsonised with IgG in monocytes from nine patients with rheumatoid vasculitis and 12 controls showed a significant reduction in Kc (p less than 0.01) but normal KFc. Kc was normal in three patients with inactive vasculitis. Low Kc was correlated with low serum C3 concentrations but not with Clq binding or anticomplementary activity, and no evidence of intracytoplasmic or membrane-bound immune complexes was detected in monocytes from patients with active vasculitis. These results show that cutaneous vasculitis in rheumatoid arthritis is associated with selective impairment of complement-mediated monocyte phagocytosis, which does not appear to result from receptor blockade by immune complexes.

Arthritis, Rheumatoid↗