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Biomedical subjects

S D Roberts

Publications and source records attributed to S D Roberts.

At least 19 recordsLinked to original sources
PubMed1992

The effect of age and acetylator phenotype on the pharmacokinetics of sulfasalazine in patients with rheumatoid arthritis.

The pharmacokinetic disposition of sulfasalazine and its metabolites was studied in 8 young and 12 elderly patients with active rheumatoid arthritis. Equal numbers of slow and fast acetylators were included in each age group. Patients received enteric-coated sulfasalazine 2g daily for 21 days; specimens of serum and urine were collected for 96 h after administration on days 1 and 21. The elimination half-life of sulfasalazine was greater in the elderly patients. Many disposition parameters of sulfapyridine differed in slow and fast acetylators; of greatest significance were the increased values of steady-state serum concentration in the slow acetylators. There was no effect of age on any sulfapyridine disposition parameters. Values for the steady-state serum concentrations of N-acetyl-5-acetylsalicylic acid were greater in elderly than in young patients. The metabolism of sulfapyridine was markedly affected by acetylator phenotype and this was reflected in the composition of sulfapyridine-related material in the urine. Thus, age is a determinant of the steady-state concentrations of salicylate moieties but acetylator phenotype plays a greater role in determining the serum concentration of sulfapyridine, which has greater therapeutic implications in rheumatology.

Acetylation↗
PubMed1991

Immunoglobulin isotype composition of circulating and intra-articular immune complexes in patients with inflammatory joint disease.

The immunoglobulin (Ig) heavy chain isotype composition of intra-articular and circulating immune complexes (ICs) were determined by a Raji cell flow cytometric assay in paired serum and synovial fluid samples from 15 patients with rheumatoid arthritis (RA) and 15 patients with other articular diseases (osteoarthritis, ankylosing spondylitis, gout, psoriatic arthritis, Reiter's disease). ICs were most prevalent in synovial fluid samples of patients with RA but were infrequently detected in serum and synovial fluid samples from the non-RA patients. ICs in patients with RA were heterogeneous both in the prevalence of Ig subclasses identified and in the distribution of the respective Ig isotypes within the complexes. Furthermore, differences were observed in the Ig isotype composition of ICs in paired serum and synovial fluid samples indicating that circulating ICs may not always arise simply by spill-over from articular sites. The possible mechanisms for IC formation in RA are discussed with reference to four patients who displayed features of extra-articular disease.

Adult↗
PubMed1989

Quantifying uncertainty in medical decisions.

Effective handling of uncertainty is one of the central problems in medical decision making. The sources and effects of uncertainty in medical decision making are examined and some new quantitative approaches for solving the associated problems are outlined. To handle uncertainty in the branching probabilities and node utilities for probability trees representing alternative treatment strategies, a public domain software package that can be used for the construction, analysis and comparison of probability trees with random parameters was developed. To facilitate specification of the random variables that arise in medical decision making problems, public domain software packages for both data-driven and subjective estimation of probability densities from the Johnson translation system of distributions have also been developed. For the analysis of complex problems that cannot be adequately represented by probability trees or by simple stochastic processes such as Markov chains, network simulation approaches that are oriented toward the sequence of activities seen by individual patients in the course of treatment are described.

Computer Simulation↗
PubMed1988

Reduction of monocyte 5'nucleotidase activity by gamma-interferon in multiple sclerosis and autoimmune diseases.

Ecto-5'nucleotidase (5'NT) activity in the plasma membrane of peripheral blood monocytes from patients with multiple sclerosis (MS), rheumatoid arthritis (RA), myasthenia gravis (MG), motor neuron disease (MND), and from normal control subjects of similar age was determined by radioisotopic assay. The activity in unstimulated monocytes cultured for 24 and 48 hours was found to be higher than normal in 56% of patients with active relapsing MS, 29% of patients with RA, and 7% of patients in the MG/MND group. While the enzyme activity was reduced after cultivation of the cells with recombinant interferon-gamma (gamma-IFN) in all of the groups studied, the percentage reduction was significantly greater in monocytes from patients with active relapsing MS who were in relapse at the time of sampling (p = 0.03). HLA-DR expression was monitored using immunofluorescence staining with monoclonal antibody and showed that similar numbers of monocytes in all patient and control groups expressed this antigen. Thus, while high monocyte 5'NT activity was found principally in patients with active relapsing MS and in some patients with RA, the monocytes from patients with MS were, in addition, exquisitely sensitive to stimulation with gamma-IFN.

5'-Nucleotidase↗
PubMed1988

Cost-effective management of patients following myocardial infarction: the impact of ischemia on alternative approaches.

Following uncomplicated myocardial infarction patients are at varying risk for cardiovascular morbidity and mortality. In order to identify and treat high risk patients, various management approaches can be employed. We performed a decision analysis to examine the cost-effectiveness of seven alternative strategies under the assumption that prognosis is affected by both the location of anatomic obstruction and the degree of myocardial ischemia. Strategies included combinations of angiography and two theoretical diagnostic tests capable of detecting ischemia with different degrees of accuracy. The strategy associated with the lowest overall six month mortality initiated testing with the diagnostic test most sensitive for ischemia, slightly better than proceeding initially to angiography. Initial use of a test sensitive for ischemia was also considerably more cost-effective than proceeding directly to angiography. Future analyses evaluating the role of diagnostic tests in coronary artery disease should incorporate the dimension of ischemia.

Coronary Disease↗
PubMed1987

Viral antibody titers. Comparison in patients with multiple sclerosis and rheumatoid arthritis.

Higher titers of antibodies to measles virus envelope antigens, hemolysin and hemagglutinin, Epstein-Barr virus (EBV) capsid antigen and nuclear antigen, and rubella virus hemagglutinin were demonstrated in serum samples of patients with multiple sclerosis and rheumatoid arthritis than in age- and sex-matched control subjects. A significant correlation was observed between antibodies to measles and rubella viruses both in patients with multiple sclerosis and rheumatoid arthritis, but such a correlation was not observed between antibodies to EBV and measles or rubella viruses. Whether elevated levels of antibodies to EBV are due to reactivation of the virus, or elevated levels of antibodies to all the enveloped viruses result from cross-reactions between viruses and host tissue, or perhaps reflect defects in immunoregulation, needs further investigation.

Adult↗
PubMed1987

Cost-effectiveness analysis of patient management alternatives after uncomplicated myocardial infarction: a model.

Quantitative decision analyses provide a means whereby the effectiveness, in terms of patient outcome, and costs of diverse clinical approaches to the care of patients with cardiovascular disease can be made explicit and understandable. Increasingly, the profession is being required to justify the costs of clinical care to society, government and third party payers. Such justifications can be effectively presented when structured in decision analytic format. To demonstrate the utility of decision analysis and its extension--cost-effectiveness analysis--as a technique for presenting the rationale for clinical practices and technology utilization, the Cardiovascular Norms Committee of the American College of Cardiology sponsored a model cost-effectiveness analysis. Alternative management options, 6 month mortality and costs for the post-myocardial infarction patient were compared. The options included exercise electrocardiography, exercise thallium scintigraphy and coronary angiography, followed by coronary artery bypass surgery for patients with left main coronary disease only or patients with left main disease, three vessel disease or single or double vessel disease and a significant amount of myocardium in jeopardy. Within the constraints of the model, proceeding directly to angiography for risk stratification was the most effective approach, lowering expected mortality from 8% to approximately 3%. The marginal costs for this strategy, however, were high. The most cost-effective approach was to screen patients initially with exercise electrocardiography.

Angiography↗
PubMed1987

The pharmacokinetics of sulphasalazine in young and elderly patients with rheumatoid arthritis.

The clinical pharmacokinetics of enteric-coated sulphasalazine (Salazopyrin-EN) were studied after acute and chronic dosing in 20 patients with 'active' rheumatoid arthritis. 12 elderly (mean age 74.4 +/- 1 yr; range 71-83) and 8 young (mean age 40.5 +/- 1.4 yr; range 35-46) patients were given a single 2 g oral dose of sulphasalazine after an overnight fast. Serum and urine samples were collected at regular intervals over a 96 hour period for estimation of concentrations of sulphasalazine, sulphapyridine and its metabolites. This procedure was repeated after 17 days of continuous treatment with salazopyrin-EN 2 g daily in order to compare the drug's kinetics at 'steady-state'. Whilst the interindividual variation in kinetic parameters was large, age and acetylator status had a significant influence on a number of factors. The elimination half-life of sulphasalazine was prolonged in the elderly whilst renal clearance was increased in slow acetylators at 'steady-state'. The tmax and apparent volume of distribution of sulphapyridine were increased in the elderly after a single drug dosage but these differences disappeared with regular dosing. The Cmax, elimination half-life, 'steady-state' serum concentration, apparent volume of distribution and total clearance of sulphapyridine were all affected by acetylator status. We conclude that old age has only a minor effect on the body's handling of sulphasalazine and sulphapyridine but that acetylator phenotype plays a significant role in determining the 'steady-state' serum concentrations of sulphapyridine. This is likely to have practical implications with regard to some of the drug's adverse effects.

Acetylation↗
PubMed1986

Cost-effectiveness of culturing for Chlamydia trachomatis. A study in a clinic for sexually transmitted diseases.

We have evaluated the cost-effectiveness of using cell culture to test for chlamydial infections in 9979 patients at a clinic for sexually transmitted diseases. From results of cultures, we have established prevalence data and, using decision-theory analysis, have calculated costs and probabilities of various outcomes. According to their histories and presenting signs and symptoms, patients were classified as at high or low risk for chlamydial infections. Empiric treatment of all patients attending the clinic was the most cost-effective strategy, followed by empiric treatment of high-risk women and culture-based treatment of low-risk women. Obtaining cultures for men at high and low risk was not cost-effective. If universal treatment is not provided, the most cost-effective strategy appears to be empiric therapy in patients at high risk for chlamydial infections and therapy based on diagnostic test results in women at low risk.

Adolescent↗
PubMed1979

Measles virus-specific antibodies and immunoglobulin M antiglobulin in sera from multiple sclerosis and rheumatoid arthritis patients.

When rheumatoid factor in rheumatoid arthritis and multiple sclerosis sera was titrated by the fluorescent antibody method on measles virus-infected cells, there was a marked and variable drop in titer on acetone-fixed cells as compared with unfixed cells. This was accounted for by the failure of measles virus hemolysin-inhibiting (HLI) antibody of the immunoglobulin G class to bind to acetone-fixed infected cells. It was shown by staining unfixed and acetone-fixed measles virus-infected cells that rheumatoid factor in most rheumatoid arthritis sera combined with measles virus-specific hemagglutinin-inhibiting and HLI antibodies, whereas rheumatoid factor in multiple sclerosis sera combined only with HLI antibody. Rheumatoid factor of similar specificity was also observed in normal sera and occasionally in rheumatoid arthritis sera. Both rheumatoid arthritis and multiple sclerosis sera showed almost identical increases in average titer above normal of measles virus-specific fluorescent staining immunoglobulin G and HLI antibodies.

Adult↗
PubMed1978

Arthritis.

Explore the source record for details and available documents.

Arthritis, Rheumatoid↗