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Biomedical subjects

J Cookson

Publications and source records attributed to J Cookson.

At least 19 recordsLinked to original sources

The face validity of a final professional clinical examination.

OBJECTIVE: To develop new methods of evaluating face validity in the context of a revised final professional examination for medical undergraduates, organized on three sites, over 2 days. METHODS: The opinion of the students and examiners was surveyed by Likert-style questionnaires, with additional open comments. Expert opinion was gathered from external examiner reports and a recent Quality Assurance Agency (QAA) Subject Review Report. RESULTS: The questionnaires had an overall response rate of 84%. Internal reliability, assessed by comparing responses to appropriate questions, was good with an equivalence of 45% (weighted kappa 0.54) for the students and 33% (weighted kappa 0.41) for the assessors. There was little evidence of inconsistency between days or sites. The majority of the opinions from the students, examiners and external experts were positive. Negative comments related to time pressure and case mix. CONCLUSION: The measurement of face validity proved feasible and valuable and will assist in the further development of the course and the examination.

Attitude↗

Use of antipsychotic drugs and lithium in mania.

Background Studies highlighting the difficulties associated with lithium suggest that the role of antipsychotic drugs and mood stabilisers in bipolar disorder should be reconsidered. Aims To review the efficacy and mode of action of antipsychotic drugs in mania, and to consider the differences between official guidelines and routine clinical practice in the use of these agents for mania. Method Review of research, guideline-and practice-based literature. Results Guidelines recommend lithium or valproate as first-line treatments for mania, and antipsychotic agents only as 'adjuncts' for agitation, dangerous behaviour or psychosis. However, in routine practice, antipsychotic drugs are often prescribed. The effectiveness of these agents in mania has been established by several studies; newer atypical compounds demonstrate antimanic efficacy with a reduced incidence of neurological side-effects. Conclusion Antipsychotic drugs are important in the treatment of bipolar disorder and mania. Future studies should evaluate the long-term efficacy and safety of newer atypical antipsychotic agents, and the place of anticonvulsants in combination with antipsychotics in bipolar disorder.

Journal Article↗

Use of antipsychotic drugs and lithium in mania.

BACKGROUND: Studies highlighting the difficulties associated with lithium suggest that the role of antipsychotic drugs and mood stabilizers in bipolar disorder should be reconsidered. AIMS: To review the efficacy and mode of action of antipsychotic drugs in mania, and to consider the differences between official guidelines and routine clinical practice in the use of these agents for mania. METHOD: Review of research, guideline- and practice-based literature. RESULTS: Guidelines recommend lithium or valproate as first-line treatments for mania, and antipsychotic agents only as 'adjuncts' for agitation, dangerous behaviour or psychosis. However, in routine practice, antipsychotic drugs are often prescribed. The effectiveness of these agents in mania has been established by several studies; newer atypical compounds demonstrate antimanic efficacy with a reduced incidence of neurological side-effects. CONCLUSION: Antipsychotic drugs are important in the treatment of bipolar disorder and mania. Future studies should evaluate the long-term efficacy and safety of newer atypical antipsychotic agents, and the place of anticonvulsants in combination with antipsychotics in bipolar disorder.

Antimanic Agents↗

The efficacy of lamotrigine in rapid cycling and non-rapid cycling patients with bipolar disorder.

BACKGROUND: Patients with bipolar disorder (BD) who have rapid cycling features are often treatment refractory. Clear and conclusive evidence regarding effective treatments for this group is not available. METHODS: Patients with diagnoses of refractory bipolar disorder who were currently experiencing manic, mixed, depressive, or hypomanic episodes were treated with lamotrigine as add-on therapy (60 patients) or monotherapy (15 patients). We compared the efficacy of lamotrigine in the 41 rapid cycling and 34 non-rapid cycling patients with BD. RESULTS: Improvement from baseline to last visit was significant among both rapid cycling and non-rapid cycling patients for both depressive and manic symptomatology. For patients entering the study in a depressive episode, improvement in depressive symptomatology was equivalent in the two groups. Among patients entering the study in a manic, mixed, or hypomanic episode, those with rapid cycling improved less in manic symptomatology than did non-rapid cycling patients. Among rapid cycling patients with initial mild-to-moderate manic symptom severity, improvement was comparable to that in non-rapid cycling subjects; however, the subset of rapid cycling patients with severe initial manic symptomatology had little improvement in mania. Rapid cycling patients had earlier onset and more lifetime episodes of mania, depression, and mixed mania. CONCLUSIONS: Lamotrigine was generally effective and well tolerated in this group of previously non-responsive, rapid cycling bipolar patients.

Activity Cycles↗

Spectrum of activity of lamotrigine in treatment-refractory bipolar disorder.

OBJECTIVE: New mood stabilizers are needed that possess efficacy for all phases of bipolar disorder. This study was designed to provide preliminary evidence for the safety and efficacy of a new anticonvulsant, lamotrigine, in adult patients with bipolar disorder who had been inadequately responsive to or intolerant of prior pharmacotherapy. METHOD: A 48-week, open-label, prospective trial was conducted in 75 patients with bipolar I or bipolar II disorder. Lamotrigine was used as adjunctive therapy (N = 60) or monotherapy (N = 15) in patients presenting in depressed, hypomanic, manic, or mixed states. RESULTS: Of the 40 depressed patients included in the efficacy analysis, 48% exhibited a marked response and 20% a moderate response as measured by reductions in 17-item Hamilton Depression Rating Scale scores. Of the 31 with a hypomanic, manic, or mixed state, 81% displayed a marked response and 3% a moderate response on the Mania Rating Scale. From baseline to endpoint, the depressed patients exhibited a 42% decrease in Hamilton depression scale scores, and the patients presenting with hypomania, mania, or a mixed state exhibited a 74% decrease in Mania Rating Scale scores. The most common drug-related adverse events were dizziness, tremor, somnolence, headache, nausea, and rash. Rash was the most common adverse event resulting in drug discontinuation (9% of patients); one patient developed a serious rash and required hospitalization. CONCLUSIONS: These open-label data provide preliminary evidence that lamotrigine may be an effective treatment option for patients with refractory bipolar disorder; however, potential benefits must be weighed against potential side effects, including rash.

Adult↗

Prothrombotic changes in children with sickle cell disease: relationships to cerebrovascular disease and transfusion.

Vascular occlusion has a central role in the pathophysiology of sickle cell disease (SCD) and, although there is little evidence that thrombosis alone is responsible, patients with sickle cell disease are known to have an ill-defined but increased thrombotic risk. The most serious complication of this in childhood is stroke which occurs in 7-10% of children and a further 14% have asymptomatic cerebrovascular disease (CVD) on imaging. We have performed a comprehensive profile of coagulation inhibitors and markers of thrombin generation in 96 children (83 nontransfused [NTx] and 13 transfused [Tx]) with steady-state SCD and 18 healthy sibling controls. The levels of protein S (free and total) and heparin cofactor II were reduced in both the NTx and Tx groups compared to controls and protein C and APC resistance ratios were reduced in the NTx group only. Antithrombin levels were not different from controls. Thrombin-antithrombin complexes and prothrombin fragment F1+2 were increased in both patient groups. In the NTx subgroups with or without CVD there were no differences for any of the parameters measured except for lower haemoglobin levels and higher white cell counts in those with asymptomatic CVD. We conclude that children with SCD have a reduction in levels of the majority of the coagulation inhibitors and increased thrombin generation in the steady-state and these are only partially reversed by transfusion. However, these abnormalities do not appear to play a primary role in the development of cerebrovascular disease.

Activated Protein C Resistance↗

Quantitative assessment of the rheumatoid synovial microvascular bed by gadolinium-DTPA enhanced magnetic resonance imaging.

OBJECTIVE: To examine the relation between rate of synovial membrane enhancement, intra-articular pressure (IAP), and histologically determined synovial vascularity in rheumatoid arthritis, using gadolinium-DTPA enhanced magnetic resonance imaging (MRI). METHODS: Dynamic gadolinium-DTPA enhanced MRI was performed in 31 patients with knee synovitis (10 patients IAP study, 21 patients vascular morphometry study). Rate of synovial membrane enhancement was quantified by line profile analysis using the image processing package ANALYZE. IAP was measured using an intra-compartmental pressure monitor system. Multiple synovial biopsy specimens were obtained by a blind biopsy technique. Blood vessels were identified immunohistochemically using the endothelial cell marker QBend30 and quantified (blood vessel numerical density and fractional area). RESULTS: Median blood vessel numerical density and fractional area were 77.5/mm2 (IQR; 69.3-110.7) and 5.6% (IQR; 3.4-8.5) respectively. The rate of synovial membrane enhancement (median 2.74 signal intensity units/s, IQR 2.0-3.8) correlated with both blood vessel numerical density (r = 0.46, p < 0.05) and blood vessel fractional area (r = 0.55, p < 0.02). IAP did not influence the rate of enhancement. CONCLUSIONS: Gadolinium-DTPA enhanced MRI may prove to be a valuable technique for evaluating drugs that influence angiogenesis.

Adult↗

Inherited prothrombotic states and ischaemic stroke in childhood.

OBJECTIVE: To investigate the prevalence of currently recognised inherited prothrombotic states in a population of children with arterial stroke. METHODS: Children with arterial stroke presenting to a tertiary level paediatric neurology centre between 1990 and 1996 were investigated for inherited prothrombotic states. RESULTS: Sixty seven children with arterial stroke were investigated. Abnormalities were initially identified in 16 patients; however, only eight children (12%) had an inherited prothrombotic state. This was type 1 protein S deficiency in one patient, the factor V Leiden mutation in six, and activated protein C resistance (without the factor V Leiden mutation) in one. The prevalence of the factor V Leiden mutation was not significantly higher in children with arterial stroke (12%) than in a control population of children without thrombosis attending the same institution (5.2%; Fisher's exact test, p=0.19; difference in prevalence between patients and controls (95% confidence interval)=6.8% (-2.78% to 16.8%)). CONCLUSIONS: Currently recognised inherited prothrombotic tendencies were rarely associated with stroke in this group of children, although larger numbers of patients would be needed to confirm this. Age appropriate normal values should be used when interpreting the results of a prothrombotic screen. Prothrombotic abnormalities seen acutely are as often transient as inherited. Longitudinal assessment and family studies are required before low concentrations of an anticoagulant protein found acutely can be attributed to an inherited abnormality.

Adolescent↗

Fluoxetine: therapeutic and undesirable effects.

The place of fluoxetine as a prototypical selective serotonin reuptake inhibitor and its marketing success have enabled extensive research on its clinical applications. This article summarizes the evidence concerning its efficacy, side-effects and toxicity.

Adolescent↗

Quantification of rheumatoid synovitis by magnetic resonance imaging.

OBJECTIVE: To develop a method for quantifying acute synovial inflammation in rheumatoid arthritis (RA), utilizing magnetic resonance imaging (MRI). METHODS: Gadolinium-diethylenetriamine pentaacetic acid-enhanced MRI was performed in 21 patients with knee synovitis. Changes in synovial membrane signal intensity were identified and quantified by line profile analysis. Multiple synovial biopsies were obtained by a blind biopsy technique, and standard clinical and laboratory measurements of disease activity were recorded. RESULTS: The rate of synovial membrane enhancement correlated with histologic features of acute inflammation (r = 0.63, P < 0.01), but not with clinical or laboratory assessments. CONCLUSION: Dynamic MRI is a valuable technique for assessing acute synovial inflammation in RA.

Adult↗

Can topical zinc accentuate tuberculin reactivity in the elderly?

We examined the effect of topical zinc on Heaf tests in 58 elderly hospitalized patients in a double-blind study. Plasma zinc levels were measured. Thirty-eight subjects (66%) had negative reactions with placebo ointment. Fourteen of these negative responders (37%) had positive reactions with topical zinc ointment; 12 (32%) had weakly positive reactions and 12 remained negative. There was no significant difference in the plasma zinc levels between the different grades of topical zinc effect in the negative responders. Zinc deficiency is therefore unlikely to account for the observed booster effect of topical zinc on tuberculin reactivity.

Administration, Topical↗

Depot antipsychotics in the prophylaxis of bipolar affective disorder.

BACKGROUND: The efficacy of depot antipsychotic drugs in the prophylaxis of bipolar affective disorder was investigated. METHOD: Life charts were constructed for 18 outpatients with bipolar disorder receiving prophylactic treatment with depot medication. The durations of affective episodes were compared during periods on or off medication. RESULTS: The subjects suffered fewer relapses and spent significantly less time in hospital (P = 0.001) for treatment of manic, depressive and mixed affective illness during treatment with depot antipsychotics. CONCLUSIONS: Depot antipsychotic medication may be a useful prophylactic treatment for certain patients with bipolar affective disorder.

Adult↗

Accurate measurement of surface areas of anatomical structures by computer-assisted triangulation of computed tomography images.

There is a need for accurate surface area measurement of internal irregular anatomical structures in order to define light dosimetry in adjunctive intraoperative photodynamic therapy (AIOPDT). No satisfactory preoperative method exists of measuring this parameter. We have investigated whether computer-assisted triangulation of serial sections generated by computed tomography (CT) scanning can give an accurate assessment of the surface area of the walls of the true pelvis after anterior resection and before colorectal anastomosis. We have shown that the technique of paper density tessellation is an acceptable method of measuring the surface areas of phantom objects, with a maximum error of 0.5%, and is used as the gold standard. Computer-assisted triangulation of CT images of standard geometric objects and accurately-constructed pelvic phantoms gives a surface area assessment with a maximum error of 2.5% compared with the gold standard. The CT images of 20 patients' pelves have been analysed by computer-assisted triangulation and this shows that the surface area of the walls varies from 143 cm2 to 392 cm2. Simple step-like analysis of images and approximation to geometric shapes with subsequent calculation give unacceptably high errors. The surface area of an internal, rigid, irregular surface area for illumination in AIOPDT can be accurately measured preoperatively by computer-assisted triangulation of CT images.

Anthropometry↗