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Biomedical subjects

R Madhok

Publications and source records attributed to R Madhok.

At least 163 records · Page 9Linked to original sources
PubMed1991

Is the beneficial effect of sulfasalazine due to inhibition of synovial neovascularization?

Angiogenesis is fundamental to support the continued synovial proliferation observed in rheumatoid arthritis. We investigated the effects of sulfasalazine and its metabolites on endothelial cell proliferation, a prerequisite to angiogenesis. At concentrations achieved in vivo sulfapyridine inhibited basal and endothelial cell growth factor stimulated endothelial cell proliferation. Sulfasalazine and 5 amino salicylic acid had no effect.

Aminosalicylic Acids↗
PubMed1991

A study of the longterm efficacy and toxicity of cyclosporine A in rheumatoid arthritis.

We determined the longterm efficacy and toxicity of cyclosporine A in rheumatoid arthritis (RA) in an open clinical trial, at a single centre, outpatient rheumatology clinic. The initial dose was 5 mg/kg/day increased to 10 mg/kg/day with adjustments for toxicity and plasma cyclosporine A levels. We measured efficacy by the Ritchie articular index, pain and function on a 10 cm visual analog scale, C-reactive protein (CRP) and erythrocyte sedimentation rate. Toxicity was evaluated by patient reports, serum creatinine, cyclosporine A levels and liver function tests. Median treatment duration was 29 months (16.5-38). At 24 months median reduction in Ritchie articular index was 50% (9-79); pain: 49% (21-77), with a 50% (4-76) improvement in function; and CRP fell by 72.5% (22-87). The main side effect was a 40% (27-47) decline in estimated creatinine clearance. We conclude that cyclosporine A at doses below 5 mg/kg/day is associated with clinically significant improvements in indices of disease activity in RA. Renal dysfunction was the most frequent side effect.

Aged↗
PubMed1990

The relationship of sulfoxidation status to efficacy and toxicity of penicillamine in the treatment of rheumatoid arthritis.

Penicillamine shows some structural similarities to carbocysteine. The ability to oxidize carbocysteine, i.e., the sulfoxidation status, shows a bimodal distribution in the general population. In this study, sulfoxidation status was determined in 50 of 60 rheumatoid arthritis patients receiving penicillamine. We found that poor sulfoxidation status, compared with good sulfoxidation status, was associated with a 3.9 times higher incidence of toxicity.

Arthritis, Rheumatoid↗
PubMed1990

HIV-1 infection in haemophilia.

Guidelines have been prepared by the National Hemophilia Foundation, USA, for treating patients with haemophilia, these are: 1. General recommendations. The risks of withholding treatment far outweigh risks of treatment. Patients should however be educated to use appropriate clotting factor doses to minimize overuse and contain costs. 2. Factor VIIIC-deficient patients. DDAVP should be used whenever possible by patients with mild or moderate factor VIIIC deficiency. When feasible, an alternative to concentrates may be the use of cryo-precipitate prepared from one well-screened donor or from a small number of such donors. (a) Prevention of hepatitis. Hepatitis B vaccination is essential for uninfected patients. Preliminary data suggest that products that are pasteurized, solvent/detergent-treated or monoclonal antibody-purified are at a reduced risk of transmitting hepatitis viruses. (b) Prevention of HIV-1. Concentrates pasteurized, treated with solvent/detergent, purified with monoclonal antibody, heated in suspension with organic solvents, or dry heat-treated for long periods are preferred. These products carry a substantially reduced risk of transmitting HIV-1. 3. Factor IX deficiency. For patients with severe deficiency the use of virus-inactivated Factor IX concentrate is recommended. For mild to moderate patients when feasible an alternative would be fresh, frozen plasma prepared from one well-screened and repeatedly-tested donor or from a small number of such donors. In the past few years, significant progress has been made in understanding the nature of the defect in haemophilia both at the molecular and structural levels, such a foundation is necessary for definitive treatments in the future. For now, however, the dark side of replacement therapy must be accepted along with its benefits.

Factor IX↗
PubMed1990

Capacity to produce interleukin 2 is impaired in haemophilia in the absence and presence of HIV 1 infection.

Capacity to produce interleukin-2 (IL-2) was measured in haemophiliacs from a well-defined treated cohort. Patients were selected on the basis of HIV-1 antibody status, mean annual dose of clotting factor and liver disease severity. T-cell subsets and peripheral blood mononuclear cell proliferation to Mycobacterium tuberculosis purified protein derivative (PPD) were also measured. Haemophiliacs had reduced IL-2 production, independent of HIV-1 antibody status, mean annual dose of clotting factor concentrate used and liver disease severity. In HIV-1 antibody positive patients reduced levels correlated with PPD proliferative responses (r = 0.6, P = 0.04) and CD8 + ve (r = 0.5, P = 0.05) but not CD4 + ve cell numbers (r = 0.3, P = 0.2). No such correlations were seen in HIV-1 antibody negative patients. Reduced IL-2 production in HIV-1 antibody negative haemophiliacs was due to a qualitative defect. In HIV-1 positive patients a qualitative defect in T lymphocytes that selectively proliferate in response to PPD was observed. CD4 + ve cell numbers were reduced in HIV-1 positive patients.

Adult↗
PubMed1990

Randomised, double blind, placebo controlled trial of inosine pranobex in rheumatoid arthritis.

In a randomised, placebo controlled, double blind study inosine pranobex was assessed as a possible second line drug in rheumatoid arthritis. Twenty four patients received inosine pranobex (3 g/day) and 26 patients received placebo for up to 24 weeks. Morning stiffness, articular index, grip strength, pain score, erythrocyte sedimentation rate, C reactive protein, IgG, IgM, and serum urate were assessed at weeks 0, 12, and 24. Baseline characteristics were similar except for a significantly higher C reactive protein in the placebo group. No significant improvement occurred in any variable: (a) when comparing week 0 with week 12 or week 24 for either group, (b) comparing active drug with placebo at week 12 or 24, or (c) taking all 50 patients as one group. Withdrawal from the study for lack of response or side effects was similar in both groups. Serum urate increased transiently but significantly with inosine pranobex (a recognised side effect). It is concluded that inosine pranobex has no second line activity in rheumatoid arthritis. Further, 50 patients effectively given placebo showed no spontaneous improvement in their disease activity.

Adult↗
PubMed1990

Further evidence that the residual vWf:Ag in porcine FVIII:C induces human platelet aggregation.

Porcine or bovine factor VIII concentrates (FVIII:C) have been used during the past 3 decades to control bleeding in patients who have developed antibodies to human factor VIII. Since current preparations of animal FVIII:C are not known to transmit infectious agents such as hepatitis or human immunodeficiency virus, they are of potential therapeutic interest. A purified porcine FVIII:C (Hyate:C) is now widely used as an alternative to human FVIII:C in patients with inhibitor. Unlike earlier preparations of porcine FVIII:C, thrombocytopaenia is rare with the current preparation. Nonetheless, it causes the aggregation of human platelets in vitro. Our aim was to identify precisely the plasma factor which induces platelet aggregation. The effects of commercial porcine FVIII:C, porcine fibrinogen, porcine fibronectin and the corresponding preparations from human origin on platelet aggregation were studied. Platelet aggregation was quantified by measuring the fall in single platelet count in human whole blood. Of these preparations, only porcine FVIII:C (0.1-1 U/ml) and porcine fibrinogen (80-600 micrograms/ml) induced a fall in single platelet count of up to 85% due to aggregation. The extent of aggregation was directly proportional to the amount (0.007-0.1 U/ml test aliquot) of residual von Willebrand factor antigen (vWf:Ag) in the preparations. A monoclonal antibody to vWf:Ag inhibited the aggregation. We believe that the aggregation of human platelets induced in vitro by porcine FVIII:C is mediated by vWf:Ag which also may be responsible for thrombocytopaenia reported following administration of porcine FVIII:C in vivo.

Animals↗
PubMed1990

Degree and extent of response to sulphasalazine or penicillamine therapy for rheumatoid arthritis: results from a routine clinical environment over a two-year period.

An attempt was made to audit the clinical usefulness of sulphasalazine and penicillamine in patients with rheumatoid arthritis (RA) managed in a routine out-patient setting with assistance from general practitioners and to ascertain whether clinically significant differences can be shown between these two 'second-line' agents. The degree and extent of change in, and the usefulness of, various parameters of disease activity were also evaluated. Two hundred patients with active rheumatoid arthritis were randomly allocated to either sulphasalazine or penicillamine and monitored for a minimum of two years. Fifty-one percent of the 102 patients who received sulphasalazine continued treatment for two years, compared with 40 per cent of the 98 patients allocated to penicillamine. The proportion of patients stopping therapy because of adverse reactions or due to lack or loss of effect was similar in the two groups. There was no difference between the two groups in the extent of improvement in clinical and laboratory variables at one and two years. The majority of patients showed improvement in most measured parameters; very few showed global improvement. The degree of improvement varied with the parameter assessed, being greatest in relatively easily measured variables such as duration of morning stiffness and ESR, and least for functional index. The effect and toxicity of these two agents in this setting was as anticipated. No clinically relevant difference could be demonstrated between the two drugs.

Arthritis, Rheumatoid↗
PubMed1989

Leucopenia during sulphasalazine treatment for rheumatoid arthritis.

Leucopenia appears to be a more frequent complication of sulphasalazine treatment in rheumatoid arthritis than in inflammatory bowel disease and poses a management problem. In this study leucopenia was found in 20 patients, 14 of whom were participating in prospective studies (252 patients), giving an incidence of 5.6%. Treatment had to be discontinued in half of these patients. Most (14) episodes of leucopenia occurred early in treatment (less than 24 weeks) but some occurred late and sustained monitoring seems necessary. No predictive factors for leucopenia were elucidated. All patients recovered fully with dose adjustment or, in more severe cases, after withdrawal of sulphasalazine and appropriate supportive therapy. The incidence of leucopenia may be higher in Glasgow than in other units in Britain.

Adult↗
PubMed1989

Histometric studies on cellular infiltrates of tuberculin tests in patients with haemophilia.

The number of microanatomical location of CD4 and CD8 lymphocytes, of cells bearing receptors for I12 and transferrin, and of monocyte/macrophages in the dermis at the site of a tuberculin test were measured in 13 patients with haemophilia (10 seronegative and three seropositive for human immunodeficiency virus (HIV]. The overall density of lymphocytes in the perivascular and diffuse parts of the infiltrate was similar to that reported in other groups of subjects without evidence of immunosuppression. The CD4:CD8 ratio of the infiltrating lymphocytes throughout the section showed an inverse relation with clotting factor consumption. There was no significant change in the CD4:CD8 ratio in the diffuse infiltrate at various levels into the dermis in tuberculin reactions in patients with haemophilia, unlike healthy controls and other groups with no evidence of immunosuppression, who have previously been shown to have increasing CD4:CD8 ratio with increasing depth into the dermis. The number of cells bearing receptors for I12 and transferrin and of monocyte/macrophages was related to total lymphocyte density in the infiltrate. There was no evidence of serious impairment of the cell mediated response to a long term recall antigen, but the relatively low preponderance of CD4 lymphocytes in the diffuse infiltrate, particularly in the deeper dermis, may be the earliest indicator of impending immunosuppression.

CD4-Positive T-Lymphocytes↗
PubMed1989

Mallet thumb: an unusual association.

A case of simultaneous mallet thumb and complete rupture of the ulnar collateral ligament of the metacarpophalangeal joint of the thumb is described. This combination of injuries has not previously been reported.

Humans↗
PubMed1989

Tips of the trade #18. How to avoid iatrogenic patella baja.

A technique for avoiding the problem of patella baja following surgery for ruptured ligamentum patellae is described. Roentgenographic comparison of the operative knee with the normal knee can guide adjusting the tension on the wire loop commonly used for splinting.

Humans↗