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Biomedical subjects

W S Mitchell

Publications and source records attributed to W S Mitchell.

At least 19 recordsLinked to original sources
PubMed1991

The role of epidural fibrosis and defective fibrinolysis in the persistence of postlaminectomy back pain.

Clinical features, contrast-enhanced lumbar tomographic findings, and biochemical plasma fibrinolytic parameters were critically assessed in 70 patients suffering severe, chronic postsurgical low-back and radicular pain to determine the cause of their persisting symptoms. Patients exhibited gross functional disability and significant impairment of plasma fibrinolytic activity, compared with 84 normal control subjects. This fibrinolytic defect appeared attributable to disproportionate increases in circulating plasminogen activator inhibitor-1 levels. Clinical features were slightly worse in patients with radiologic epidural fibrosis, whereas the frequency of radiologic abnormalities, including epidural fibrosis, was higher in patients with fibrinolytic abnormalities. The results, however, demonstrated no significant associations between patients' symptoms and signs and their biochemical and radiologic abnormalities.

Arachnoiditis↗
PubMed1991

Fibrinolytic enhancement with stanozolol fails to improve symptoms and signs in patients with post-surgical back pain.

An open trial with the fibrinolytic enchancing agent stanozolol was completed by eighteen patients (14 male) with severe back and radicular pain, despite previous lumbar surgery for prolapsed intervertebral disc. Assessments of their pain, disability and plasma fibrinolytic activity were undertaken before and after 12 or 24 months of therapy. Prior to treatment patients exhibited significant fibrinolytic abnormalities when compared with 84 normal controls; euglobulin clot lysis time (ELT) 442 vs 157 mins and fibrin plate lysis area (FPLA) 61 vs 113 mm2 respectively (p less than 0.01 for both). Stanozolol therapy normalised patients' fibrinolytic activity within three months. Disappointingly there were no concomitant clinical improvements in spinal pain or mobility despite 12 or 24 months of treatment. These results may indicate that perineural fibrosis, once formed, is not amenable to such therapy.

Adult↗
PubMed1989

Skin blood flow and limited joint mobility in insulin-dependent diabetes mellitus.

Hand skin blood flow in 32 insulin-dependent (IDDM) diabetics was compared with 13 healthy controls at room temperature and after immersion of the hands in warm and cold water. Subjects were examined for limited joint mobility (LJM) to analyse the association between this and blood flow. Digital arteries remained patent in IDDM compared to controls after cold challenge (p = 0.0001), and the difference persisted to a lesser degree 15 min (p = 0.009) and 30 min (p = 0.03) after recovery. Capillary blood flow was reduced in IDDM at room temperature at the finger nailbeds (p less than 0.02) and the palms (p = 0.004) and remained so after warm water immersion in the palms (p = 0.002), where further vasoconstriction was observed immediately after cold water immersion (p less than 0.001) and 15 and 30 min into recovery (p = 0.07 and p = 0.009 respectively). Thermographic analysis confirmed a pattern of predominantly distal rewarming after cold challenge in IDDM with a greater mean index finger temperature than the controls. Together, these features suggested enhanced arteriovenous anastomotic blood flow. All IDDM and IDDM males with LJM had reduced palm capillary flow immediately after cold challenge (p less than 0.05). After warm water (p less than 0.03) and 30 min after cold challenge (p less than 0.05) IDDM males with LJM had reduced palm capillary flow compared to those IDDM without. A microvascular aetiology for LJM is proposed by virtue of reduced nutritional blood flow and evidence of enhanced arteriovenous shunting in the hands of insulin-dependent diabetics.

Adolescent↗
PubMed1989

Ketanserin: an effective treatment regimen for digital ischaemia in systemic sclerosis.

We have studied the therapeutic effects of ketanserin, a specific serotonin antagonist, on digital ischaemia in 11 patients with the CREST syndrome of systemic sclerosis. Ketanserin was administered as a bolus of 10 mg intravenously, followed by an infusion over 72 h and then oral therapy. Skin blood flow as measured by thermography, bolometry, ultrasound Doppler pulses and laser light scattering, showed significant improvement. There was also marked clinical improvement with a reduction in the pain and healing of digital ulceration. These improvements were maintained on oral therapy. In 7 patients detailed studies were performed comparing oral and intravenous ketanserin therapy. When ketanserin was administered as a bolus 10 mg intravenous dose, followed by an infusion at 2 mg/h, steady state was reached by 12 h. Following oral treatment (40 mg tds) therapeutic blood levels were achieved.

Administration, Oral↗
PubMed1988

Altered hand skin blood flow in type 1 (insulin-dependent) diabetes mellitus.

Disturbed upper limb skin blood flow has been described in insulin-dependent (Type 1) diabetes mellitus, but the pathophysiological mechanism remains unclear. Hand skin blood flow was therefore measured at room temperature and following immersion of hands in cold and warm water in 13 healthy control subjects, in 10 patients with Type 1 diabetes mellitus and cardiovascular autonomic neuropathy, and a further 10 Type 1 diabetic patients with normal cardiovascular autonomic tone. Following cold challenge there was failure of digital artery clampdown in all diabetic patients in comparison with healthy control subjects (p less than 0.005), and the index finger temperature fell less (p less than 0.05). Laser Doppler flow was reduced at the palms at room temperature or following the warm challenge (p less than 0.008), as well as on the dorsum at room temperature (p less than 0.05), in all diabetic patients. In addition laser Doppler flow in the diabetic patients was reduced at the palms and dorsum immediately following cold water challenge (p less than 0.004) and this reduction persisted 15 min (p less than 0.05) and 30 min (p less than 0.01) into the recovery phase. In comparison to those diabetic patients with normal cardiovascular tone, those with cardiovascular autonomic neuropathy had reduced laser Doppler flow at the pulp 15 min after cold water immersion (p less than 0.05), at the nailbed immediately after cold water immersion (p less than 0.01), and at the palms immediately after warm water challenge (p less than 0.01).

Adult↗
PubMed1986

An inhibitor of complement-mediated prevention of immune precipitation in rheumatoid arthritis--relationship to disease activity and systemic manifestations.

In normal serum complement prevents precipitation of antigen-antibody complexes (PIP). However rheumatoid arthritis (RA) serum contains an inhibitor of this complement-mediated function. We have undertaken two prospective studies in order to look for any relationship between the presence and levels of inhibitory activity in sera and synovial fluids (SF) of patients with RA and disease activity (study A), and the presence of systemic manifestations (nodules and vasculitis) of RA (study B). In study A, levels of inhibitory activity were highest in the sera and synovial fluids of patients with seropositive RA. However there was no correlation between the inhibitory levels and indices of generalised disease activity (articular index, erythrocyte sedimentation rate (ESR), haemoglobin, white cell and platelet counts). Local joint tenderness score correlated weakly with the inhibitory level in SF (P less than 0.05). There was no correlation, however, with either the SF protein concentration or white cell count. In study B, PIP was shown to be lower in patients with the systemic manifestations of RA than in those with purely articular manifestations. PIP was particularly low in those patients with vasculitis compared to those with subcutaneous nodules. Serum levels of inhibitory activity were highest in patients with vasculitis and lowest in those with articular disease only, whereas patients with nodules had intermediate levels. Our conclusion is that inhibition of immune precipitation is not associated with disease activity, but is associated with the extra-articular manifestations of RA. The inhibitory factor may play a role in the pathogenesis of RA.

Antigen-Antibody Complex↗
PubMed1984

Inhibition of immune precipitation in rheumatic disease. A clinical and laboratory study.

Antigen-antibody complexes formed in the presence of serum do not precipitate. This complement-dependent function is impaired in approximately half of all patients with seropositive rheumatoid arthritis (RA) but not in patients with other chronic inflammatory arthropathies. As patients with seropositive RA have normal or elevated serum complement levels, this findings suggests that an inhibitor is present in the serum of these patients. Although degree of impairment of solubilization is correlated with rheumatoid factor (RF) titre, decreases in RF titre in patients receiving gold therapy were not always accompanied by improvement of the solubilization process. Thus we can conclude that impaired solubilization is related to, but may be distinct form, RF. Impaired solubilization was associated with the presence of subcutaneous nodules, but not with other systemic features of RA. Thus this phenomenon may be of pathogenetic importance.

Antigen-Antibody Complex↗
PubMed1984

IgM-RF prevents complement-mediated inhibition of immune precipitation.

Rheumatoid arthritis (RA) serum inhibits complement-mediated inhibition of immune precipitation (solubilization). We have isolated inhibitory activity from RA sera and shown that it is a property of IgM-rheumatoid factor (IgM-RF) and, to a lesser extent, IgG-RF.

Antigen-Antibody Complex↗
PubMed1983

Complement-mediated inhibition of immune precipitation in patients with immune complex diseases.

The ability of human sera to prevent the precipitation of antigen-antibody complexes has been investigated. The early complement components including C3 are required for optimal prevention of immune precipitation, whereas the later components are not required. The sera of 36 of 75 patients with seropositive rheumatoid arthritis (RA), 14 of 32 with SLE and four of 17 with glomerulonephritis exhibited reduced capacities to prevent immune precipitation. In contrast sera from patients with seronegative RA, ankylosing spondylitis, psoriatic arthritis or degenerative joint disease were normal in this respect. In SLE and GN sera hypocomplementaemia was frequently associated but not always with failure to prevent immune precipitation, whereas only a small proportion of the patients with seropositive RA and reduced capacity to retain complexes in a soluble form were hypocomplementaemic. Thus the failure of sera to prevent the precipitation of antigen-antibody complexes is not always associated with hypocomplementaemia.

Antigen-Antibody Complex↗
PubMed1983

Inhibition of complement-mediated solubilization of antigen-antibody complexes by sera from patients with rheumatoid arthritis.

Sera and synovial fluids from patients with seropositive rheumatoid arthritis inhibit the ability of normal serum to prevent immune precipitation. Sera from patients with seronegative forms of arthritis contain little inhibitory activity. Studies of the mechanism of action of the inhibitor show that it reduces C4 consumption by antigen-antibody complexes. These findings suggest that the binding of C1 to complexes or activation of C1 is impaired. The possibility that the inhibitory activity may be mediated by rheumatoid factor is discussed. As inhibitory activity is more prevalent and of a higher level in patients with extra-articular features, it is possible that it may play a pathogenetic role.

Antigen-Antibody Complex↗
PubMed1978

Contingency learning in chronic schizophrenia and its relevance to social motivation deficit.

The present study investigates the ability of chronic schizophrenic patients to learn to obtain social rewards when the incentive value of the contingent social event is known. From a group of 40 chronic patients tested for responsivity to social rewards, socially responsive and socially unresponsive patients were selected and compared on a learning task. Patients who were highly motivated to obtain social reinforcement did not emit the reinforced response during 300 learning trials any more frequently than did patients who were not motivated by social rewards. It was only when the experimental contingency was specified that responsive and unresponsive patients could be differentiated. The implications of these findings for social motivation theories of schizophrenia are discussed.

Adult↗
PubMed1976

Septic arthritis in patients with rheumatoid disease: a still underdiagnosed complication.

Eight cases of septic arthritis occurring in patients with rheumatoid arthritis are reviewed. The difficulty in diagnosis of this condition is due in part to a failure of these patients to respond normally to infection. Consequently patients often present late in the course of their septic episode and treatment is often delayed. The importance of early diagnosis and treatment of the infection is stressed by the high mortality rate in this group of patients. Many factors operate to encourage infection in rheumatoid arthritis and the current concepts of the problem are reviewed.

Aged↗
PubMed1975

The effects of prostaglandins PGE1, PGE2, PGF1a, and PGF2alpha on canine synovial perfusion.

In these experiments we have examined the effects of PGE1, PGE2, PGF1alpha and PGF2alpha on synovial perfusion in the normal canine synovial microcirculation. The effects of the drugs on synovial perfusion were determined indirectly from the changes produced in the rate of clearance of 133Xenon from the joint by their intra-articular injection. Prostaglandins PGE1 and PGE2 were found to be strongly vasodilator with PGE1 being the more active. PGF1alpha appeared to have little or no vasoactive properties in doses up to 1 ugm. (2.8 times 10(-5M)) in our preparation while PGF2alpha was vasodilator at this high dosage only. Neither SC19920 nor diphloretin phosphate antagonished the effects of PGE1 in these experiments.

Animals↗