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Biomedical subjects

G Nuki

Publications and source records attributed to G Nuki.

At least 19 recordsLinked to original sources
PubMed1994

Leg ulceration in rheumatoid arthritis.

Chronic leg ulcers occur in 1% of the adult population with considerable associated morbidity, and community costs estimated at up to 600 million pounds p.a. in the UK. Leg ulcers appear to be relatively common in patients with RA and are widely believed to be resistant to treatment. Such ulcers are often attributed to vasculitis, but little is known of the occurrence of other potential aetiological factors. This article reviews the epidemiology, natural history and aetiology of chronic leg ulcers in RA as well as the therapeutic options available.

Adult↗
PubMed1994

Nonsteroidal anti-inflammatory drugs in the treatment of osteoarthritis.

Symptoms and disability vary considerably over time and among individuals with similar degrees of radiographic osteoarthritis. The results of recent clinical studies have reaffirmed that many patients prefer nonsteroidal anti-inflammatory drugs (NSAIDs) to analgesics while also demonstrating that many individuals who have been receiving NSAIDs can manage without them. Certain but as yet poorly characterized patients appear to respond more favorably to treatment with NSAIDs. Thus, both chronic unquestioning use of NSAIDs and denial of NSAIDs to individuals with osteoarthritis are extreme and inappropriate approaches to treatment. Concerns about the gastrointestinal toxicity of NSAIDs remain, although strategies to prevent this toxicity provide some reassurance and should be considered for use in individuals who are at particular risk. These strategies include the use of NSAIDs that are selective inhibitors of the prostaglandin endoperoxide synthase II isoenzyme and are potentially less ulcerogenic or the coprescription of prostaglandin analogues or other ulcer-healing drugs. The costs and benefits of such approaches have yet to be established. Cartilage metabolism is adversely affected by certain NSAIDs in vitro, but the relevance of these observations remains unclear. In our view, the judicious use of NSAIDs in the treatment of osteoarthritis is acceptably safe and indicated in individuals in whom pain cannot be managed by simple analgesics and nonpharmacologic approaches.

Analgesics↗
PubMed1994

Interleukin 1 beta, hand and foot bone mineral content and the development of joint erosions in rheumatoid arthritis.

OBJECTIVE: To assess the relationship between plasma levels of the cytokine interleukin-1 beta (IL-1 beta) and the progression of rheumatoid arthritis (RA). METHODS: Two subgroups of patients, one with persistently raised ESR (>/= 50 mm/hour, n = 16, group A) and one with persistently low ESR (</= 28 mm/hour), n = 18, group I) were chosen to represent stable extremes of inflammatory activity from a prospective study of 106 patients with active RA studied over one year in a single centre. The change from baseline in hand, foot and calcaneal bone mineral content measured by single photon absorptiometry and radiographic score of joint damage was measured over 12 months, together with plasma IL-1 beta and erythrocyte sedimentation rate. RESULTS: Significant progression of joint damage occurred in both subgroups over one year (p < 0.0001, paired t test) though progression was significantly less in the subgroup with low ESR (p < 0.05, ANOVA). Hand and foot bone mineral content decreased by almost 10% in the subgroup with raised ESR (p < 0.005, paired t test). Stepwise linear regression analysis revealed significant independent relationships between radiographic progression over one year and plasma IL-1 beta and ESR (multiple R 0.674, F = 11.64, p < 0.0002). No such relationships were observed for changes in bone mineral content parameters. CONCLUSIONS: Plasma IL-1 beta levels correlate weakly with progression of joint damage though not with loss of peripheral bone density in RA. A significant reduction in peripheral bone mineral content occurs over one year in patients with active RA with persistently raised ESR.

Adult↗
PubMed1992

The point mutation of hypoxanthine-guanine phosphoribosyltransferase (HPRTEdinburgh) and detection by allele-specific polymerase chain reaction.

The change in DNA responsible for partial hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency in three brothers has been determined by polymerase chain amplification and sequencing. An A-to-G substitution at base 155 in exon 3 predicts a change in aspartic acid 52 to glycine. Allele-specific polymerase chain amplification verified the presence of the mutation in genomic DNA and provides a means of direct diagnostic assay.

Adolescent↗
PubMed1992

Systemic and mucosal antibodies to Klebsiella in patients with ankylosing spondylitis and Crohn's disease.

Whole gut lavage fluid is a useful source of material for the study of intestinal immunity and inflammation in humans. Systemic and mucosal antibodies to Klebsiella pneumoniae were measured by enzyme linked immunosorbent assay (ELISA) in serum samples and whole gut lavage fluid from 14 patients with ankylosing spondylitis, 14 with Crohn's disease, and 16 immunologically normal controls. As the concentration of IgG in whole gut lavage fluid reflects disease activity in Crohn's disease, this approach was used to detect intestinal inflammation in patients with ankylosing spondylitis who also had disease activity and use of non-steroidal anti-inflammatory drugs (NSAIDs) recorded. Small intestinal permeability to cellobiose and mannitol was also studied. In serum samples, levels of IgA antibody to klebsiella were high in patients with Crohn's disease and in patients with active ankylosing spondylitis, and were significantly correlated with the erythrocyte sedimentation rate in patients with ankylosing spondylitis. Levels of IgG antibody to klebsiella were also high in patients with Crohn's disease. Studies of whole gut lavage fluid showed similar levels of IgA antibody to klebsiella in the three study groups, but levels of whole gut lavage fluid IgM and IgG antibodies to klebsiella were high in patients with Crohn's disease. Levels of IgG in whole gut lavage fluid were high in patients with Crohn's disease but in only one patient with ankylosing spondylitis, though the cellobiose/mannitol permeability ratio was abnormal in eight of 13 patients with ankylosing spondylitis. It is concluded that high levels of serum IgA antibody to klebsiella are not specific to ankylosing spondylitis, and that there is no evidence of an abnormal intestinal IgA antibody response to klebsiella in patients with ankylosing spondylitis.

Adult↗
PubMed1992

Multicentric reticulohistiocytosis with arthritis and cardiac infiltration: regression following treatment for underlying malignancy.

The case is reported of a 63 year old man presenting with a rapidly destructive symmetrical polyarthritis and widespread papular nodular skin lesions, confirmed by a biopsy to be due to multicentric reticulohistiocytosis. Biventricular cardiac failure developed secondary to extensive myocardial infiltration with multicentric reticulohistiocytosis, a complication of this disease which has not previously been reported. The joint, skin, and cardiac manifestations of multicentric reticulohistiocytosis substantially regressed following resection of an associated squamous cell carcinoma. This report adds to the small amount of published work which suggests that multicentric reticulohistiocytosis can be a paraneoplastic disease that may respond to treatment directed at the underlying tumour.

Arthritis↗
PubMed1992

Response of plasma membrane to applied hydrostatic pressure in chondrocytes and fibroblasts.

Effects of applied hydrostatic pressure on transmembrane potentials were investigated in sheep articular chondrocytes and human skin fibroblasts in non-confluent monolayer cultures. Resting potentials in chondrocytes (about -12 mv) and in fibroblasts (about -15 mV) were increased and decreased respectively by over 40% after pressure was applied cyclically (0.33 Hz, 120 mm Hg, 20 minutes). Continuous pressure (120 mm Hg, 20 minutes) caused deplorization in both cell types. Low frequency pressure application (less than 0.08 Hz) caused depolarization in chondrocytes and hyperpolarization in fibroblasts. Quinidine (2 x 10(-5) M) blocked and verapamil (10(-5) M) reduced hyperpolarization responses, suggesting involvement of Ca(2+)-dependent K+ channels. A23187 (1.9 x 10(-6) M) caused hyperpolarization in chondrocytes, augmented further by subsequent pressure application (0.33 Hz). Tetrodotoxin (10(-6) M) blocked depolarization responses indicating that these were due to Na+ influx. Blockade of histamine H1 receptors by chlorpheniramine maleate (5.1 x 10(-6) M), H2 receptors by cimetidine (7.9 x 10(-6) M) and beta-adrenoreceptors by sotolol (1.3 x 10(-4) M) had no effect on hydrostatic pressure-induced hyperpolarization in chondrocytes. Cytochalasin B (2 x 10(-5) M and at 4 x 10(-6) M) abolished pressure-induced hyperpolarization in chondrocytes; in contrast, applied cyclical hydrostatic pressure to cytochalasin-treated fibroblasts caused hyper-polarization, suggesting that cytoskeletal changes were involved.

Animals↗
PubMed1991

Resonant frequency at the wrist in hypermobile women.

The resonant frequency of the wrist has been measured in sixteen hypermobile and nine normal women at ten levels of peak torque. At the lowest level the results were identical but at the others the hypermobile values were lower. Damping and thixotropy appeared to be normal. In another group the grip strength of hypermobile subjects was similar to that of controls. The possibility that the connective tissue of the musculature of hypermobile subjects is of enhanced compliance is discussed.

Adult↗
PubMed1990

Pain control and the use of non-steroidal analgesic anti-inflammatory drugs.

Rheumatic complaints, particularly associated with osteoarthritis, are responsible for about one third of all General Practice consultations in people over the age of 65 and non-steroidal anti-inflammatory drugs (NSAIDs) are used on a vast scale for pain relief. Although the individual risk to life is small NSAIDs are the major cause of serious adverse reactions (ADRs) reported to drug regulatory authorities and ADRs are more common and more serious in the elderly. Gastric ulceration, haemorrhage and perforation are the major concern but fluid retention, renal and hepatic failure, asthma, skin reactions, bone marrow suppression and a host of drug interactions can occur. NSAIDs are responsible for a fifth of all admissions to hospital with bleeding or perforated peptic ulcer and thousands of deaths worldwide. Strategies for minimising the risks of ADRs are discussed and emphasis is placed on using minimal analgesic, rather than anti-inflammatory, doses of short-acting NSAIDs and where possible avoiding their use in high risk patients. For the future cytoprotection with prostaglandin analogues may have a role to play.

Aged↗
PubMed1990

A multicentre double-blind comparison of auranofin, intramuscular gold thiomalate and placebo in patients with psoriatic arthritis.

The efficacy and safety of the oral gold compound auranofin and intramuscular gold thiomalate have been compared in a placebo-controlled, double-blind, four-centre trial in 82 patients with psoriatic arthritis requiring remittive drug therapy. There were statistically significant falls in Ritchie articular index, visual analogue pain score and ESR at 12 and 24 weeks following i.m. gold but no significant changes in the auranofin group. Intramuscular gold was safe and more effective than auranofin as a second-line, suppressive antirheumatic agent for patients with psoriatic arthritis when followed for 6 months.

Adult↗
PubMed1989

Hypoxanthine-guanine phosphoribosyltransferase deficiency in three brothers with gout: characterization of a variant, HPRTEdinburgh, having altered isoelectric point, increased thermal lability and normal levels of messenger RNA.

Three brothers who developed acute gouty arthritis at ages 16, 20 and 26 years were found to have increased plasma urate. Erythrocyte hypoxanthine phosphoribosyltransferase (HPRT) activity was less than 1% of normal and adenine phosphoribosyltransferase (APRT) activity was increased 2-3-fold. This variant, HPRTEdinburgh, was further studied using lymphoblast lines established from these patients and the following observations are consistent with a mutation involving a single amino acid substitution. Lymphoblasts from these patients had 0.9-1.6% of control HPRT activity which was 8-fold more labile than control activity at 75 degrees C. Isoelectric focusing of the variant protein in polyacrylamide gels indicated a pI of 6.5-6.7 which is more basic than normal HPRT, pI 6.0-6.3. The Michaelis constants were increased: 10-fold for hypoxanthine from 1.3 to 13 mumol/L, and 5-fold for PP-ribose-P from 6 to 30 mumol/L, for control and variant respectively. The Ki for product inhibition by GMP was marginally increased in the variant. Northern blot analysis of variant lymphoblast RNA indicated normal amounts of the expected 1.6 kilobase messenger RNA.

Adolescent↗
PubMed1989

Biodynamics of the wrist in rheumatoid arthritis--the enigma of stiffness.

The wrist has been moved rhythmically in the horizontal plane by sinusoidal torques provided by a printed motor. Measurements have been made on normal subjects and subjects with rheumatoid arthritis. Both groups exhibited a resonance, the oscillations being greatest when the applied torque was of certain frequency. In both groups the resonant frequency fell to approximately the same constant value when the torque was raised. While the main relationships were similar a somewhat lower torque resulted in the lowering of resonant frequency in the patients. The relationship between applied torque and peak velocity at resonance was also studied. For a given torque the motion was greater in the patients. No objective signs of increased viscous or elastic stiffness were demonstrable at the wrist in patients with rheumatoid arthritis.

Arthritis, Rheumatoid↗
PubMed1988

Tumour necrosis factor in synovial exudates.

The actions of tumour necrosis factor (TNF) include resorption of bone and cartilage, suggesting a potential role in the pathogenesis of arthritis. TNF activity was looked for in synovial fluids from 137 patients with different rheumatic diseases. Unfractionated samples were tested in the L929 bioassay. Significant TNF activity that was neutralised by monoclonal antibody to TNF alpha occurred in 13 (30%) of 44 samples. Raised TNF levels were not associated with any particular disease type or routine laboratory markers of inflammation but were related to disease duration in osteoarthritis. The finding of biologically active TNF in symptomatic joints of arthritic patients supports the idea that it may contribute to the pathogenesis of joint damage in chronic rheumatic diseases.

Biological Assay↗