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P Jobanputra

Publications and source records attributed to P Jobanputra.

At least 37 records · Page 2Linked to original sources
PubMed1996

Effects of intermittent pressure-induced strain on the electrophysiology of cultured human chondrocytes: evidence for the presence of stretch-activated membrane ion channels.

1. Cyclical pressurization of cultured chondrocytes results in increases in cyclic AMP and in the rate of proteoglycan synthesis. Intermittent increases in hydrostatic pressure are also associated with hyperpolarization of chondrocyte cell membranes and activation of Ca(2+)-dependent K(+)-ion channels but the physiological basis for this response to mechanical stimulation is unclear. 2. Experiments have been undertaken to better define the types of ion channels involved and to explore the possibility that the hyperpolarization response associated with cyclical pressurization of chondrocytes follows activation of stretch-activated ion channels. 3. The mean membrane potential of chondrocytes in non-confluent monolayer cell culture rose from -15.3 +/- 0.24 mV to -21.1 +/- 0.28 mV (n = 60, P < 0.0001) after intermittent pressurization (0.33 Hz, 16 kPa, 20 min). 4. Strain gauge measurements showed that cyclical pressurization was associated with strain on the base of the culture plate. The amplitude of the hyperpolarization response was proportional to the microstrain to which cells were subjected. 5. Membrane hyperpolarization did not occur when chondrocytes were subjected to cyclical pressurization in rigid glass culture dishes or plastic dishes positioned in the pressurization chamber so as to avoid bending of the base of the culture dish. 6. Indirect evidence that the hyperpolarization response after intermittent pressure-induced strain was associated with stimulation of stretch-activated ion channels was obtained from experiments with gadolinium, amiloride and hexamethylene amiloride, each of which abolished hyperpolarization. 7. Experiments with apamin, charybdotoxin and iberiotoxin showed that the Ca(2+)-activated K+ channels involved in the hyperpolarization response are apamin-sensitive, charybdotoxin- and iberiotoxin-resistant, low-conductance channels. 8. Somatostatin and cadmium chloride, which block L-type calcium channels, abolished strain-induced chondrocyte hyperpolarization. EGTA, which chelates extracellular Ca2+, reduced the response to 48% of control values, and thapsigargin, which raises intracellular Ca2+ by inhibition of Ca(2+)-ATPase in endoplasmic reticulum, caused hyperpolarization independently with further hyperpolarization after pressure-induced strain. These data indicate that chondrocyte hyperpolarization was dependent on intracellular Ca2+ concentrations. 9. Further work is required to determine whether stretch-activated ion channels shown to be associated with chondrocyte hyperpolarization after cyclical pressure-induced strain are also involved in the signal transduction process that leads to increases in proteoglycan synthesis.

Calcium Channels↗
PubMed1995

An audit of methotrexate and folic acid for rheumatoid arthritis. Experience from a teaching centre.

We describe an audit of 158 patients with RA treated with weekly methotrexate and 5 mg of folic acid 24 h later. Our aim was to assess the safety and efficacy of this regime in our hands compared with published clinical trials of methotrexate in RA, and to examine patient outcomes. Treatment improved ESR, but only 69% of patients continuing therapy for prolonged periods believed their arthritis to be better on treatment. Health Assessment Questionnaire and Hospital Anxiety and Depression questionnaire scores in prospectively studied patients were not significantly altered by treatment. Toxicity occurred frequently (59% in those continuing and 89% in those ceasing therapy) and cessation of therapy solely due to lack of efficacy was rare. The probability of patients continuing with methotrexate and folic acid after 1, 2, 3 and 4 yr was 87, 76, 74 and 74%, respectively, figures that are at the upper end of the reported range for methotrexate alone.

Adult↗
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

Validity of Euroqol--a generic health status instrument--in patients with rheumatoid arthritis. Economic and Health Outcomes Research Group.

The main aim of this pilot study was to test the 'construct' validity of Euroqol, a new generic health status instrument which consists of a questionnaire and visual analogue scale. Its ability to measure both current health status and change in health status was assessed in 55 patients with RA. The Euroqol questionnaire and visual analogue scales showed significant and clinically relevant correlations with other condition-specific instruments measuring loss of function, joint pain, joint tenderness and mood; change in these symptoms as measured by the condition-specific instruments was also predictive of change in Euroqol scores. Either component of the Euroqol instrument provide an index of current clinical status and these data provide preliminary evidence for the 'construct' validity of Euroqol in RA. Further work is needed to evaluate more fully the sensitivity of Euroqol to change over time.

Adolescent↗
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↗
PubMed1992

Cellular responses to human chondrocytes: absence of allogeneic responses in the presence of HLA-DR and ICAM-1.

To assess the accessory cell function of human articular chondrocytes, we assessed the ability of human chondrocytes to stimulate allogeneic peripheral blood mononuclear cells (PBMC) and to support phytohaemagglutinin (PHA)-induced proliferation of highly purified T cells. We also examined the surface expression of HLA-DR and ICAM-1 on the chondrocytes both unstimulated and stimulated with cytokines in vitro. Chondrocytes failed to stimulate allogeneic PBMC despite the constitutive expression of MHC class I molecules and the cytokine-induced expression of class II molecules but were able to support T cell proliferation to PHA, IFN-gamma and to a limited extent, IL-1 beta, induced class II expression on chondrocytes. ICAM-1 was present on 94-99% of freshly isolated cells; this declined with culture (17-59%; P < 0.005) but was readily induced by IFN-gamma, IL-1 beta, and tumour necrosis factor-alpha. Alloreactivity and, presumably, autoreactivity to chondrocytes requires factors in addition to the surface expression of DR and ICAM-1. However the presence of these molecules suggests a capacity for cell-cell interactions in inflammatory sites such as the cartilage pannus junction.

Antigen-Presenting Cells↗
PubMed1992

Cellular immunity to cartilage proteoglycans: relevance to the pathogenesis of ankylosing spondylitis.

Cellular immunity to cartilage proteoglycans may be responsible for sustaining chronic inflammation in ankylosing spondylitis. This hypothesis was examined by measuring peripheral blood and synovial fluid mononuclear cell proliferation in five preparations of human cartilage proteoglycan monomer in vitro. Peripheral blood mononuclear cells from 25 patients and synovial fluid mononuclear cells from five patients were compared with those from normal and disease control subjects matched for age. No significant differences were found between the three groups. This suggests that autoimmune responses to cartilage proteoglycans are unlikely to play a significant part in the pathogenesis of ankylosing spondylitis.

Adult↗
PubMed1992

General practice rheumatology.

A survey of 1000 consecutive patients presenting with a new complaint in general practice was carried out to determine the frequency and types of rheumatic problems encountered and the treatments required. Sixty-three (6.3%) of these were for rheumatic complaints. Of these 43% involved the lower back. Soft tissue disorders were predominant and 54% of patients were managed with advice and reassurance only. This suggests that a greater emphasis on these disorders is necessary for doctors in training. During a minimum follow-up period of 3 months, seven (11%) of the 63 patients were referred for specialist opinions.

England↗
PubMed1991

Lyme disease.

Explore the source record for details and available documents.

Arthritis, Infectious↗
PubMed1991

Management of acute asthma attacks in general practice.

A prospective study was carried out in a semirural group practice between June 1988 and December 1989 to investigate acute asthmatic attacks treated with nebulized salbutamol. Questionnaires were completed by the attending doctor and by the patient (or his or her parent). Sixty nine episodes, occurring in 52 patients, were recorded during the 18 month study period. The majority of the attacks were managed exclusively in the community, with hospital admission occurring on only three occasions, one patient being admitted twice. A large proportion of the patients had a severe attack of asthma as judged by their previous history. Oral steroids were prescribed in 62.3% of attacks, oral theophyllines in 31.9% and antibiotics in 37.7%; the salbutamol nebulizer was used on more than one occasion during 41.2% of attacks. Significant morbidity was experienced by the patients during the studied attack, with 85% suffering sleep disturbance and two thirds being unable to attend work or school. Only 52.5% of patients were on prophylactic treatment and 37.5% of the patients had discontinued some aspect of their asthma therapy in the three months prior to the attack. Patients' and doctors' views about the cause of the attacks differed widely: patients most commonly cited infection (26/41) and allergy (8/41) with only two patients citing poor compliance or inadequate treatment. Although doctors also attributed the cause of many attacks to infection (33/64), they cited poor compliance or inadequate treatment in 28 of 64 responses.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1990

A controlled trial of sulphasalazine treatment of chronic ankylosing spondylitis: failure to demonstrate a clinical effect.

Sixty-two patients with long established but symptomatic ankylosing spondylitis were treated with sulphasalazine or matching placebo in a randomized double-blind controlled trial for 48 weeks. There were no consistent significant differences between the treatment groups in clinical parameters despite multiple assessments. Equivalent numbers in each group were able to decrease or stop non-steroidal anti-inflammatory drug ingestion during the study period (four active, eight placebo). Side effects were reported more commonly in the sulphasalazine group (27 versus 17, NS), but only 21 patients stopped treatment because of side effects (12 versus 9, NS). Analysis of the subgroup with an initial ESR greater than 20 mm/h failed to show any persisting differences of response between sulphasalazine and placebo. We conclude that sulphasalazine therapy does not have a role in the treatment of chronic ankylosing spondylitis.

Chronic Disease↗