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Biomedical subjects

G Nuki

Publications and source records attributed to G Nuki.

At least 73 records · Page 4Linked to original sources
PubMed1986

Corticosteroids and bone mass in asthma: comparisons with rheumatoid arthritis and polymyalgia rheumatica.

Bone mass has previously been shown to be reduced at peripheral bone sites in patients with bronchial asthma receiving corticosteroids. To assess whether total bone mass is reduced in asthma total body calcium was measured by in vivo neutron activation analysis in patients receiving various treatments for asthma and compared with results from normal controls and patients with rheumatoid arthritis and polymyalgia rheumatica. Compared with controls total body calcium was reduced by 13.6% (p less than 0.001) in patients with asthma receiving daily oral corticosteroids but by only 9.0% (p less than 0.005) in a similar group of patients who had received oral calcium supplements at the start of their corticosteroid treatment. Total body calcium was also reduced in a group of patients receiving only inhaled corticosteroids (8.8%; p less than 0.001) but not significantly reduced in a small group of patients with asthma who had never received these drugs. When compared with controls a group of patients matched for age and for dose of corticosteroids given for rheumatoid arthritis had a similar reduction in total body calcium to the patients with asthma receiving daily oral treatment (17.7%; p less than 0.001), but no such reduction was shown in patients with polymyalgia rheumatica. These findings suggest that the risk of bone loss with low dose oral corticosteroids in similar in asthma and rheumatoid arthritis. Further work is required to assess the clinical relevance of small losses of bone associated with the use of inhaled corticosteroids.

Administration, Oral↗
PubMed1986

Differential effects of mepacrine, chloroquine and hydroxychloroquine on superoxide anion generation, phospholipid methylation and arachidonic acid release by human blood monocytes.

The 4-aminoquinolines chloroquine (CQ) and hydroxychloroquine (HCQ), and previously the 9-aminoacridine mepacrine (quinacrine) (MP), have been widely used in the treatment of inflammatory disorders such as rheumatoid arthritis and systemic lupus erythematosus. Their effects are believed to be mediated through phagocytic cells but the precise biochemical basis remains uncertain. We have investigated the effects of these drugs on monocyte superoxide anion (SO) generation elicited by 5 different stimuli-opsonised zymosan (STZ), FMLP, A23187, TPA and fluoride--and sought correlations with effects on two processes which have been linked with monocyte activation, namely arachidonate (AA) release and transmethylation of phosphatidyl ethanolamine (PE) to phosphatidylcholine (PC). In all experiments conditions were adjusted to achieve leucocyte concentrations of drug comparable to those found during in vivo therapy. Neither CQ nor HCQ had any marked effect on SO release induced by TPA, A23187 or fluoride ion, excluding a significant effect on protein kinase C (PKC), calmodulin-dependent kinase(s) or the membrane-bound, superoxide generating NADP(H) oxidase. In contrast MP inhibited the response to TPA and A23187. Each drug also had different effects on surface receptor-dependent responses; thus HCQ inhibited FMLP- but not STZ-induced SO release, whereas CQ and MP inhibited the response to both stimuli. Each drug also displayed different effects on AA release and phospholipid (PL)-methylation; MP and HCQ, but not CQ, inhibited STZ-stimulated AA release while MP and CQ but not HCQ inhibited basal rates of PL-methylation in mononuclear cells (MNC). However, only MP inhibited PL-methylation in an enriched monocyte population. We conclude that despite their close structural similarity, MP, CQ and HCQ each have different metabolic effects and their actions cannot simply be attributed to inhibition of lysosomal functions. Other possible mechanisms of action are discussed. The selective effects of each drug also provide further evidence for multiple pathways of monocyte activation.

Arachidonic Acid↗
PubMed1986

Distribution of an anti-DNA idiotype among autoantibodies in patients with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA).

Autoantibodies from patients with systemic lupus erythematosus, rheumatoid arthritis, or other connective tissue disorders were probed for the presence of a cross-reactive idiotype (AM Id) originally defined on human anti-double-stranded DNA antibodies. The AM Id was distributed primarily among antibodies to double-stranded DNA, single-stranded DNA, or cardiolipin in patients with systemic lupus erythematosus and antibodies to single-stranded DNA or cardiolipin and rheumatoid factor in patients with rheumatoid arthritis, thus tending to codistribute with the predominant primary autoantibodies in both diseases. Strong associations were observed particularly between the AM Id and anti-single-stranded DNA antibodies in patients with systemic lupus erythematosus and the AM Id and anticardiolipin antibodies in patients with rheumatoid arthritis. Affinity absorption experiments with sera from individual lupus patients showed that up to 41% of the anti-single-stranded DNA antibodies were Id positive. The results indicate that the AM Id may be widely distributed among antibodies that have a potential for binding DNA.

Antibodies, Anti-Idiotypic↗
PubMed1986

Total and peripheral bone mass in patients with psoriatic arthritis and rheumatoid arthritis.

Psoriatic arthritis is thought to be associated with periarticular osteoporosis while rheumatoid arthritis may be associated with generalised as well as periarticular bone loss. To assess the extent of total and peripheral bone loss in these two diseases, total body calcium was measured by in vivo neutron activation analysis and peripheral bone mass was assessed by metacarpal indices in age-matched patients with psoriatic arthritis and rheumatoid arthritis treated with nonsteroidal anti-inflammatory drugs alone. In comparison with age and sex-matched normal controls, total and peripheral bone mass was normal in psoriatic arthritis. There were significant reductions in total (6.2% in men; 7.9% in women) and peripheral (10.9% in men; 12.8% in women) bone mass in patients with rheumatoid arthritis compared with controls. Peripheral bone mass was significantly correlated with the degree of radiographic damage in male and female patients with rheumatoid arthritis. The mean annual loss of total body calcium was insignificant in psoriatic arthritis (0.6% in men; 1.9% in women) but markedly greater in rheumatoid arthritis (4.4% in men; 2.7% in women). The data suggested that total and peripheral bone loss is greater in rheumatoid arthritis than psoriatic arthritis. Substantial reductions in peripheral bone mass in patients with rheumatoid arthritis not receiving corticosteroids may account in part for the small reductions in total bone mass.

Adult↗
PubMed1986

Cross-reactive idiotypes in anti-DNA antibodies of systemic lupus erythematosus patients.

Cross-reactive idiotypes associated with the combining site of anti-double-stranded DNA antibodies from systemic lupus erythematosus patients were demonstrated by the ability of isologous lupus sera to block functionally the binding of target anti-DNA antibodies to DNA in vitro. A framework idiotype, denoted AM Id, was identified using xenogeneic anti-idiotype antibodies rendered specific by affinity absorptions. The AM Id was found in 85% of patients with systemic lupus erythematosus (n = 63) and correlated positively with anti-DNA antibodies. Analysis of the distribution of the AM Id among individuals showed that, while present in anti-DNA antibodies to varying degrees in individual patients, it was also found in variable amounts on non-DNA-binding immunoglobulins. These results indicate that the AM Id and anti-DNA antibodies represent overlapping populations of immunoglobulins.

Antibodies, Anti-Idiotypic↗
PubMed1986

The seasonal variation of total body calcium.

Total body calcium was measured using in vivo neutron activation analysis in 156 patients with rheumatic diseases at six-month intervals. Evidence of seasonal variation was sought by relating deviation from a linear change to the month in which the measurement was made. A cyclic regression fitted to the data had an amplitude of 0.25% but a significance of only P = 0.08. The calcium balance studies of Malm were re-analysed to quantify the seasonal variation he had demonstrated in one group of men. The deduced variations of body calcium were highly significant, with a phase and amplitude very similar to the regression of our data. Both analyses differed from two previous reports of seasonal variations of part-body bone mineral of much greater amplitude and different phase.

Calcium↗
PubMed1986

Bone loss in rheumatoid arthritis and primary generalized osteoarthrosis: effects of corticosteroids, suppressive antirheumatic drugs and calcium supplements.

The annual rate of bone loss in rheumatoid arthritis (RA) and primary generalized osteoarthrosis (PGOA) was determined by measurement of total body calcium (TBCa). The mean annual rate of bone loss in 24 patients with RA treated with nonsteroidal anti-inflammatory drugs (NSAIDs) alone was 3.4%. This rate of bone loss was not reduced in ten RA patients responding to suppressive antirheumatic drugs (4.3%) or seven patients receiving oral calcium supplements (4.5%). The mean annual rate of loss of TBCa in 19 patients with PGOA was 1.6%, a figure which probably represents age-associated bone loss. The rate of bone loss in PGOA was significantly less than that in RA patients not receiving corticosteroids. The mean annual rate of change of TBCa in 30 RA patients receiving corticosteroids (+0.7%) was significantly less than that in any of the other RA groups despite an initial normalized bone mass which was significantly less than in those RA patients receiving NSAIDs alone. The data supported the hypothesis that bone loss occurred early in the course of corticosteroid therapy and thereafter the drugs might have a protective effect on the loss of bone in RA.

Adrenal Cortex Hormones↗
PubMed1986

Effect of corticosteroid therapy on blood monocyte superoxide generation in rheumatoid arthritis: studies in vitro and ex vivo.

Rates of superoxide (SA) generation by blood monocytes stimulated ex vivo were studied before and during corticosteroid treatment of rheumatoid arthritis (RA) patients, in control patients and in healthy controls. The direct effect on stimulated SA production of pre-incubating cells with prednisolone in vitro was also studied. Significant inhibition of monocyte SA output stimulated with IgG-treated zymosan (ITZ) and fluoride ion (F), but not serum-treated zymosan (STZ) was demonstrated following steroid therapy in RA. No inhibitory effect of prednisolone could be demonstrated in vitro, using ITZ, STZ and F as stimuli. Our data on blood monocyte yields, size and cytochemistry suggest that the in vivo effect is due to a shift in blood monocyte traffic.

Adrenal Cortex Hormones↗
PubMed1986

Interleukin 1 activity produced by human rheumatoid and normal dendritic cells.

Dendritic cells (DC) from the synovial inflammatory tissue and peripheral blood of patients with rheumatoid arthritis and from the peripheral blood of normal blood donors were compared with the autologous monocytes for their capacity to produce and release interleukin 1 (IL-1). Synovial DC often spontaneously released higher amounts of IL-1 activity than unstimulated and lipopolysaccharide-stimulated peripheral blood DC and monocytes. The IL-1 production by both DC and monocytes increased after stimulation with bacterial lipopolysaccharide. In contrast with synovial DC the peripheral blood DC from both patients with rheumatoid arthritis and normal controls released less IL-1 activity than peripheral blood monocytes did. Inhibition with an antiserum to IL-1 revealed that IL-1 production is important for the accessory activity of the peripheral blood DC. Thus human DC from inflammatory sites and peripheral blood produce IL-1 activity.

Arthritis, Rheumatoid↗
PubMed1986

Studies of the effect of D-penicillamine and sodium aurothiomalate therapy on superoxide anion production by monocytes from patients with rheumatoid arthritis: evidence for in vivo stimulation of monocytes.

The capacity of monocytes from patients with rheumatoid arthritis to generate superoxide anion in vitro after stimulation with serum treated zymosan (STZ) or IgG treated zymosan (IgTZ) was studied before and during therapy with penicillamine (n = 9) or sodium aurothiomalate (AuTM) (n = 12). Significant increases in rates of STZ (p less than 0.01) and IgTZ (p less than 0.02) stimulated superoxide anion production were seen after successful therapy (14 patients), which were paralleled by a significant increase in serum thiol levels. Patients who did not respond clinically to therapy (n = 4) showed a smaller mean increase in serum thiol levels and had high mean rates of in vitro superoxide production before and after second-line therapy. Three patients were withdrawn from the study. The data suggest that successful therapy with penicillamine or AuTM may be associated with monocyte activation, and possible mechanisms are discussed.

Arthritis, Rheumatoid↗
PubMed1986

Bone mass in ankylosing spondylitis.

To assess bone mass in ankylosing spondylitis (AS) we have measured total body calcium, bone mineral content of the lumbar spine and metacarpal indices in groups of patients with AS. Mean total body calcium was reduced by 5.3% (p less than 0.05) in 20 patients compared with controls. The mean annual loss of bone, assessed over an 18 month period in 17 patients, was 2.9% (p less than 0.001). Compared to controls, bone mineral content was increased by 28% (p less than 0.05) in 8 male patients while metacarpal indices were normal in 18 male and female patients. The results of total body calcium measurements give support to the hypothesis of a minor increase in bone turnover in AS. The increased bone mineral content in the male patients may relate to syndesmophyte formation.

Adult↗
PubMed1985

Screening for antimalarial maculopathy in rheumatology clinics.

Ophthalmoscopy and three tests of visual function were undertaken in 39 patients with rheumatoid arthritis receiving treatment with antimalarial drugs and in a control group of 16 patients with rheumatoid arthritis who were not receiving such treatment. Visual contrast sensitivity, macular threshold to red light, and central visual fields to red targets were not significantly different in treated patients and controls. There were no abnormalities in visual acuity, but 11 of 76 eyes of treated patients showed minor macular abnormalities on ophthalmoscopy that were not seen in control patients, suggesting that ophthalmoscopy may be the most sensitive measure of early drug toxicity. Five rheumatologists were able to identify 52 of 65 minor changes detected by an ophthalmologist. These studies, and a critical review of published reports, suggest that in clinical practice antimalarial drugs can be administered safely to patients with rheumatoid arthritis without the need for repetitive routine examination by an ophthalmologist or the use of complicated physiological tests. Recording of visual acuity in each eye and ophthalmoscopy by the prescribing doctor may be all that are required to detect early antimalarial maculopathy.

Adult↗
PubMed1985

Erythema nodosum following typhoid vaccination.

Erythema nodosum has recently been recognised in association with salmonella infection (1). We report a case of classical erythema nodosum which developed following a typhoid vaccination.

Erythema Nodosum↗