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Biomedical subjects

W S Mitchell

Publications and source records attributed to W S Mitchell.

18 recordsLinked to original sources

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

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

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

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

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

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

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

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

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

Mothers and their disturbed preschool children: an intervention study.

Children who had attended a unit for disturbed preschool children were followed up and compared to a group of children whose families had turned down the offer of a place at the unit. Measures of home and school behaviour and of social stress factors operating on the family were collected. Although treated and control children were comparable on severity of symptoms on referral, treated children showed a greater reduction in reported problem behaviour at home than did controls by the time of the follow-up interview. Attendance at the unit had a limited effect on behavior at school, however. It is suggested that if a treatment for preschool children is to have broad goals including increased competence at school as well as a reduction in problem behaviour at home, then various treatment strategies should be devised to meet these different goals.

Child Behavior Disorders

A behavioural programme for the modification of encopresis.

This paper describes a behaviour modification programme for the treatment of encopresis. The programme, which is carried out by the parents over a relatively short period of time in the home setting, aims to make the child aware of internal cues prior to elimination and to rearrange the contingencies for appropriate use of the toilet. To date, seven of eleven children, both continuous and discontinuous encopretics, have been treated successfully and have remained clean for up to 7 months regardless of other problems in the child and his family. From a relatively detailed analysis of those treated it can be concluded that a behavioural approach is effective with chronic encopretic children, many of whom had been previously treated unsuccessfully by both physical and psychotherapeutic procedures. The failures suggest, firstly that careful assessment of each child and the motivation of the parents is required, so that the standard programme can be modified to suit each individual case. Secondly a maintenance programme must follow the intensive treatment procedure to ensure that parents continue to handle the child consistently.

Behavior Therapy