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Biomedical subjects

D L Scott

Publications and source records attributed to D L Scott.

At least 181 records · Page 10Linked to original sources

Injections and physiotherapy for the painful stiff shoulder.

Cost effective treatment is needed for common self limiting rheumatological conditions. Periarthritis of the shoulder is an example. There is no consensus for one type of treatment, though local steroids or physiotherapy are conventionally used. Their cost and efficacy were compared in a prospective randomised observer-blind trial--in essence a medical audit of the treatment of a common rheumatological problem. Sixty two consecutive patients presenting with a painful stiff shoulder were studied. Patients with coexistent diseases like cervical spondylosis or a stroke were excluded. They were randomly allocated to receive local steroids, six weeks' physiotherapy, or both. The three groups were of similar age, sex, and disease severity. Assessments of pain and shoulder movement were made initially, at six weeks, and at six months by a 'blinded' observer. Physiotherapy was given by one therapist and injections by one physician. All three groups showed significant improvements by six weeks, with further improvement at six months. Improvements were identical in all three groups. No treatment gave complications. The costs of treatment varied: an injection of triamcinolone cost 2.10 pounds; a six week course of physiotherapy cost 48.50 pounds; combination treatment cost 50.60 pounds. Patients expect treatment for a painful stiff shoulder. The results show that local steroid injections are as effective as physiotherapy alone or a combination. They provide rapid treatment and are less expensive. In the uncomplicated case a local steroid injection is the most cost effective treatment.

Costs and Cost Analysis↗

What proteins are present in polyethylene glycol precipitates from rheumatic sera?

The proteins present in 4% polyethylene glycol (PEG) precipitates of 10 normal sera and 60 samples from patients with rheumatic diseases were studied. A variety of immunochemical methods were used, including estimation of the percentages of total serum proteins precipitated by PEG, gel filtration analyses of the precipitates, and affinity chromatography with protein A and anti-immunoglobulin columns. Substantial amounts of protein were precipitated from normal sera. Many non-immunoglobulin proteins were precipitated from patients' sera, including fibronectin, haptoglobin, albumin, transferrin, and alpha 1-antitrypsin. Affinity chromatography with anti-immunoglobulin columns bound non-immunoglobulin proteins from PEG precipitates, but the protein A affinity column did not do so. The view that circulating antibody-antigen complexes alone are precipitated by 4% PEG is too simplistic; many non-immunoglobulin proteins are involved. They may either bind to immune complexes or be coprecipitated owing to non-specific protein aggregation.

Adolescent↗

Plasma fibronectin in Crohn's disease.

The hypothesis that abnormal fibronectin metabolism in Crohn's disease could be an important mechanism leading to stricture formation or postoperative infection was tested in three related studies. (1) Lower concentrations of plasma fibronectin (p less than 0.05) were found in 20 patients with small and large bowel Crohn's disease (mean 0.24 g/l) compared with 13 patients with more limited disease confined to only small or only large bowel (mean 0.27 g/l) or 20 healthy controls (mean 0.29 g/l). (2) In 25 patients followed for 10 days after operation for Crohn's disease, there was a significant fall in fibronectin concentrations of 43% (p less than 0.01, Wilcoxon's rank-sum test). This fall was maximal on the second postoperative day and was more marked in patients undergoing more major operative procedures. (3) The predictive value of plasma fibronectin for subsequent stricture formation or progression was studied for one year; during which 10 patients developed strictures requiring operative treatment. Higher plasma fibronectin concentrations were related to stricture formation, although there was not a complete, predictive relationship. In this study we found that plasma fibronectin concentrations were low in patients with extensive or severe Crohn's disease, fall after operation and may be related to the risk of stricture formation. This relationship is unlikely to be of clinical value, although it shows the potential significance of fibronectin in the pathogenesis of strictures.

Adult↗

Etodolac therapy for osteoarthritis: a double-blind, placebo-controlled trial.

The efficacy of etodolac (600 mg/day) and placebo were compared in a 4-week double-blind, parallel-group study involving 104 patients with osteoarthritis of the knee and 106 with osteoarthritis of the hip. Most patients had improvement of their symptoms during the study, but significantly more improvement was seen in the patients taking etodolac. Patients with osteoarthritis of the knee taking etodolac had significantly (p less than 0.05) more improvement than placebo-treated patients in joint swelling, weight-bearing pain, and patient's overall assessment. Patients with osteoarthritis of the hip taking etodolac had significantly (p less than 0.05) greater improvement than placebo-treated patients in hip abduction, weight-bearing pain, joint tenderness, investigator's overall assessment, and patient's overall assessment. The frequency of adverse events was not statistically different in the two treatment groups. However, significantly (p = 0.05) more etodolac-treated patients (n = 9) than placebo-treated patients (n = 2) reported indigestion. The incidence of adverse events was similar in patients aged 65 years and older to that in patients younger than 65 years. Results of laboratory evaluations indicated that etodolac therapy was associated with no more hepatic or renal enzyme abnormalities than was placebo.

Adult↗

Progressive joint damage during penicillamine therapy for rheumatoid arthritis.

Progressive joint damage characterises rheumatoid arthritis despite treatment with slow-acting drugs such as penicillamine. We examined a cohort of 145 RA patients, treated with 250 or 500 mg penicillamine daily for 18 months to study progressive joint damage measured using Larsen's standard radiographs. Overall damage increased significantly over 18 months at both doses of penicillamine. Radiological changes between 6-18 months were studied in detail in 55 cases. They were divided into rapidly progressive (increases in Larsen score of more than 5) or slowly progressive (increases in Larsen score of 5 or less). Overall clinical response, visual analogue pain score, ESR, haemoglobin and platelet count were significantly lower in the slowly progressive patients; articular index and duration of morning stiffness were slightly lower; latex titre, RAHA titre, joint size and white cell count showed no differences between groups. There is an indirect relationship between progressive joint damage and some clinical and laboratory measures. The reasons underlying our failure to control progression in some cases need further definition.

Adult↗

The clinical value of measuring immunoglobulins when assessing penicillamine therapy in rheumatoid arthritis.

Immunoglobulins are often high in active rheumatoid arthritis and fall when treatment with a slow-acting anti-rheumatic drug is instituted. We assessed the value of monitoring immunoglobulins during penicillamine therapy; 145 patients were followed for up to 5 years, IgA, IgM and IgG levels were compared to 12 other clinical and laboratory variables on 903 occasions. Mean levels of IgA and IgG fell by 10-30%. These changes were less than with ESR or clinical measures such as articular index and duration of morning stiffness. Immunoglobulin levels showed weak correlations with other variables. Only a small number of patients had hypogammaglobulinemia. Initially, 5 cases had low IgA with subsequent falls in 3 more. Initially, 2 cases had low IgG with subsequent falls in 5 more. No patients had low IgM levels. These changes seemed clinically irrelevant. Radiological progression was related to IgA levels. Patients with persistently high rates of radiological progression had persistently higher serum IgA. We conclude that IgM gives the most "acute phase" pattern of response. IgA gives more theoretically interesting information, especially concerning radiological progression. There is only a limited amount of clinically valuable information gained from measuring immunoglobulins.

Adult↗

Vasculitis in Reiter's syndrome.

A patient is described with both Reiter's syndrome and cutaneous vasculitis characterised by livedo reticularis. The development of the Reiter's syndrome immediately preceded the onset of vasculitis. It is suggested that Reiter's syndrome is a previously unrecognised potential cause of vasculitis in which infection may initiate the vasculitic reaction.

Adult↗

Nucleosides and bases in synovial fluid from patients with rheumatoid arthritis and osteoarthritis.

1. Nucleosides and bases in physiological fluids result from metabolism of nucleic acids and nucleotides and from dietary sources. As nucleotide catabolism increases during tissue injury, nucleosides and bases could serve as useful biochemical markers in arthritis. 2. We have quantified nucleosides and bases in synovial fluid and plasma by high-performance liquid chromatography in order to examine whether nucleotide metabolism is increased in patients with rheumatoid arthritis and osteoarthritis. 3. At least ten u.v.-absorbing compounds were detected in plasma and synovial fluid; only urate, creatinine, hypoxanthine and uridine were present in identifiable and quantifiable amounts. 4. In synovial fluid from patients with rheumatoid arthritis the concentration of hypoxanthine was increased and that of urate decreased compared with osteoarthritis. 5. These data suggest that there is an increase in purine metabolism in the rheumatoid arthritis joint and that hypoxanthine is a potential marker of synovitis.

Adult↗

P component in the synovium in rheumatoid and osteoarthritis.

P component is present in amyloid deposits, normal serum, and normal tissues in relation to elastic fibres. Its pathological role in inflammatory synovitis was investigated. Its distribution was determined immunohistologically in 33 synovia: 15 rheumatoid; seven osteoarthritic; seven traumatic controls; and four infected biopsy specimens. P component was present in two circumscribed distributions: extracellular fibrils in dense fibroelastic tissue of the more fibrotic synovia; and in the arterial wall, where it was confined to a single elastic lamina in some cases and in others showed reduplication and fragmentation. These were not related to amyloid material. It shows no disease specificity, but P component categorises the nature of the pathological reaction and is typically in biopsy specimens showing the development of chronic fibrosis. There was close codistribution of P component with elastic tissue, though this was not absolute. P component had a different distribution from C reactive protein (in synovial lining cell layer), and fibronectin, which was absent from fibrotic areas. Understanding the pathological interactions of P component may help elucidate why some synovial reactions remain inflammatory and other progress to chronic fibrosis.

Arthritis, Rheumatoid↗

Adverse reactions to sulfasalazine: the British experience.

Sulfasalazine has been used for a decade in the United Kingdom for treating rheumatoid arthritis. There is now considerable experience with its adverse reaction profile and the incidence of serious events. In the initial weeks of treatment minor side effects are common, especially upper gastrointestinal problems and nausea. Therapy is thus usually introduced slowly and enteric coated tablets are preferred. In 20-30% of patients treatment is discontinued due to an adverse reaction. Most of such reactions occur within 3 months of starting therapy, are trivial, and are self-limiting after withdrawal of the drug. Potentially more serious adverse reactions include leukopenia, rash, abnormal liver function tests, and dyspnea. These reactions also reverse after treatment is stopped. Side effects leading to drug withdrawal after 1 year of therapy are unusual.

Arthritis, Rheumatoid↗

Long-term outcome of treating rheumatoid arthritis: results after 20 years.

Outcome of therapy, in terms of functional capacity, radiological measures of joint damage, erythrocyte sedimentation rate (ESR), rheumatoid factor, and mortality, was determined prospectively in 112 consecutive rheumatoid arthritis (RA) patients treated for 20 years at one centre, where a policy of active treatment was pursued with the use of gold, chloroquine, steroids, and, in resistant cases, penicillamine or cytotoxic drugs. By 20 years 35% were dead. Mortality was often attributable to RA. Function improved in the early years of treatment but declined considerably between 10 and 20 years. At 20 years 19% were severely disabled. Radiographs showed related evidence of increasing joint destruction. The ESR and rheumatoid factor levels changed little. Age, late presentation, and rheumatoid factor seropositivity at presentation were poor prognostic factors. The concept of "remission-inducing" drugs is fallacious. Early treatment may be advantageous, but the prognosis of RA is not good.

Adult↗

ELISA assays for IgM and IgG rheumatoid factors: their clinical correlations during therapy with slow-acting anti-rheumatic drugs.

A longitudinal study of changes in rheumatoid factor levels and their correlations with other clinical and laboratory assessment of disease activity followed 45 rheumatoid arthritis patients during 12 months continuous therapy with gold and penicillamine. Rheumatoid factors were measured by the titred latex assay and by ELISA assays for IgM and IgG rheumatoid factor. The IgM ELISA assay correlated strongly with the titred latex assay and weakly with the IgG rheumatoid factor assay at 0, 6 and 12 months. All showed significant falls with treatment, and ELISA assays were not more sensitive indicators than the latex assay. Correlations of initial rheumatoid factor levels by all 3 assays to 34 other clinical and laboratory assessments showed that only a small number of weak correlations existed; there were more at 6 and 12 months, but still not many. Changes in rheumatoid factor levels over 0-6 months showed no significant correlation to changes in other variables. There were no more correlations with ELISA assays than with titred latex rheumatoid factor. We conclude that ELISA rheumatoid factor assays have no clinically relevant advantage over the titred latex assay when following rheumatoid patients treated with gold or penicillamine.

Arthritis, Rheumatoid↗

A method to assess concomitant cardiac phosphodiesterase inhibition and positive inotropy.

The ability of positive inotropic drugs to inhibit phosphodiesterase was assessed by observance of the potentiation of inotropic responses to the low intrinsic efficacy beta-adrenoceptor partial agonist prenalterol. Previous studies have shown that an increase in tissue stimulus response capability, as is produced for beta-adrenoceptors by blockade of phosphodiesterase, produces an increase in the maximal response to beta-adrenoceptor partial agonists. Using this principle, we tested cardiotonic drugs on normal and prenalterol-pretreated guinea pig left atria and compared the resulting inotropic responses statistically. Prenalterol pretreatment did not potentiate inotropic responses to methoxamine and CaCl2 and blocked (in accordance with beta-adrenoceptor occupation by a low-efficacy partial agonist) responses to norepinephrine (NE), tyramine, and to a certain extent ouabain. This latter finding was attributed to a low-level catecholamine-release by ouabain in this tissue. The inotropic responses to the phosphodiesterase inhibitors isobutylmethylxanthine (IBMX), theophylline, and enprophylline were greatly potentiated. Similarly, the responses to the cardiotonic drugs (known also to be inhibitors of phosphodiesterase) milrinone, amrinone, and fenoximone were potentiated. Positive inotropy to the cardiotonic drug sulmazole was not significantly potentiated by this procedure, indicating that in this tissue sulmazole may produce inotropic responses by other mechanisms as well. In general, this simple assay may be useful to detect blockade of cardiac phosphodiesterase concomitant with positive inotropy. Although a causal relationship between the PDE inhibition and positive inotropy may not be made from these data, knowledge of PDE blockade may still be useful in the assessment of inotropic mechanism and propensity for toxic side effects.

1-Methyl-3-isobutylxanthine↗