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J Firth

Publications and source records attributed to J Firth.

34 records · Page 2Linked to original sources
PubMed1992

Using changes in attributable risk to predict long-term efficacy of simvastatin treatment.

It is a common perception that coronary heart disease (CHD) deaths will decline by 2% for every 1% decrease in serum total cholesterol (TC). We investigated the changes in serum TC concentrations obtained with simvastatin, an inhibitor of hydroxymethylglutaryl-CoA reductase, in 70 hypercholesterolemic subjects. Although simvastatin reduced serum TC concentrations by 30% after 6 months, calculations from age- and risk-related TC quintiles show that the absolute difference in attributable CHD deaths would be just > 1%. These results are reminiscent of the experience from several large prospective primary drug trials that demonstrated impressive relative benefit ratios but much smaller absolute differences (< 2%) in CHD endpoints between the treated and untreated groups. This epidemiologically based approach of assessing efficacy and potential long-term benefit of a lipid-lowering drug may be more appropriate and potentially less misleading than just the percentage change of TC (or other lipoproteins) so frequently reported in short-term drug trials.

Adult↗
PubMed1991

Determination of 4-hydroxyandrost-4-ene-3,17-dione metabolism in breast cancer patients using high-performance liquid chromatography-mass spectrometry.

A sensitive procedure for studying the metabolism of the steroidal aromatase inhibitor 4-hydroxy-androst-4-ene-3,17-dione (4OHA) was developed based on enzyme hydrolysis, liquid-liquid extraction and reversed-phase liquid chromatography coupled with a mass spectrometer (LC-MS) using a thermospray interface. Seven metabolites were identified from the hydrolysed urine samples together with the parent drug. The major routes of metabolism were via dehydrogenation, reduction of the ketone functional groups, reduction at the C-4-C-5 double bond and hydroxylation at the C-5 position. Confirmation of the identity of 4OHA and its metabolites isolated from female patients' urine samples was accomplished by comparison of the retention times of their corresponding synthetic standards on LC-MS. We have demonstrated that this technique is particularly suitable for studying the metabolism of steroidal drugs.

Administration, Oral↗
PubMed1991

Primary non-Hodgkin's lymphoma of the central nervous system: phase II study of chemotherapy (BVAM) prior to radiotherapy.

Ten patients were diagnosed as having primary non-Hodgkin's lymphoma of the central nervous system at University Hospital, Nottingham, between September 1986 and April 1989. None had clinical evidence of HIV-1 infection. All the patients started treatment with chemotherapy (BVAM), designed to cross the blood-brain barrier, followed by radiotherapy. Seven patients completed both chemotherapy and radiotherapy. Dose reduction during chemotherapy was necessary in three patients because of neutropenia. In two of the six patients with solitary tumours, complete resection was achieved surgically prior to treatment. Five of the remaining eight patients (63%) had radiological evidence of a complete response with chemotherapy. The other three patients had no response to chemotherapy but one had a complete response after radiotherapy. The two-year cause-specific survival of the 10 patients was 37%. Two of the three patients who had a postoperative performance status of 0 or 1 (ECOG/WHO) are alive and disease-free at 26 and 46 months from diagnosis. The median survival of the seven patients with a performance status of 2-4 was 10 months with two patients alive and disease-free at 19 and 26 months. The two-year cause-specific survival of these seven patients was 22%.

Adult↗
PubMed1987

Prescriptive v. exploratory psychotherapy. Outcomes of the Sheffield Psychotherapy Project.

Prior research suggests that psychotherapeutic techniques which differ in their contents are quite similar in their outcomes. Outcome data are reported from a study designed to maximise sensitivity to technique effects on outcome in a clinically realistic setting, and to permit detailed analysis of the relations between content, immediate impact, and outcome of therapy. Forty professional and managerial workers with depression or anxiety received eight sessions of Prescriptive (cognitive/behavioural) and eight sessions of Exploratory (relationship-oriented) therapy in a crossover design, with each client seeing the same therapist throughout. Outcome was assessed by standard interview and questionnaire methods. The results favoured Prescriptive therapy, although this difference was of moderate extent. The outcome was largely unaffected by the order in which the two methods were offered.

Anxiety Disorders↗
PubMed1987

Disposition of 3H-enisoprost, a gastric antisecretory prostaglandin, in healthy humans.

1. After oral administration of 3H-enisoprost (450 micrograms) to five healthy men, as a solution in capsules, peak 3H levels of 5624 +/- 566 pg equiv./ml (mean +/- S.E.M.) were reached within one hour. No unchanged drug was detected in plasma. 2. Enisoprost was rapidly de-esterified to SC-36067 [(+/-)11 alpha, 16 zeta-dihydroxy-16-methyl-9-oxoprost-4Z, 13E-dien-1-oic acid], a pharmacologically active analogue, which reached peak concentrations of 651 +/- 200 pg/ml within 20 min of dosing. SC-36067 was eliminated metabolically, with a half-life of 1.61 h, by a combination of beta-oxidation, omega-oxidation and 9-keto-reduction. 3. After nine days 59.0 +/- 2.98% and 17.4 +/- 1.57% of the dose was excreted in urine and faeces respectively. The majority of this excretion was complete in two days. 4. Five urinary metabolites were identified by GC-MS. These were (+/-)3-[2 beta-(4-hydroxy-4-methyl-1E-octenyl)-3 alpha-hydroxy-5-oxo-1 alpha-cyclopentanyl]propanoic acid (SC-41411; 3.6% dose), (+/-)3-[3 alpha,5-dihydroxy-2 beta-(4-hydroxy-4-methyl-1E-octenyl)-1 alpha-cyclopentanyl]propanoic acid (SC-41411 PGF analogue; 4.8% dose), (+/-)3-[2 beta-(8-carboxy-4-hydroxy- 4-methyl-1E-octenyl)-3 alpha-hydroxy-5-oxo-1 alpha-cyclopentanyl] propanoic acid (SC-41411-16-carboxylic acid; 22% dose), (+/-)3-[2 beta-(8-carboxy-4- hydroxy-4-methyl-1E-octenyl)-3 alpha,5-dihydroxy-1 alpha-cyclopentanyl] propanoic acid (SC-41411 PGF analogue-16-carboxylic acid; 8.5% dose) and its gamma lactone (2.6% dose). 5. These metabolites were also identified chromatographically in plasma, as were SC-36067, (+/-)3-[2 beta-(4-hydroxy-4-methyl-1E-octenyl)-5-oxo-1 alpha- cyclopent-3-enyl]propanoic acid and (+/-)3-[2 beta-(4-hydroxy-4-methyl-1E-octenyl)-5-oxo-cyclopent-1- propanoic acid. 6. Some 5-10% of the dose was excreted in urine as tritiated water, indicating that oxidation of the 11 alpha-hydroxy group in SC-36067 or its metabolites also occurred.

Adult↗
PubMed1986

Levels and sources of stress in medical students.

Levels of stress, as measured by the general health questionnaire, were assessed in 318 medical students in their fourth year at three British universities. Mean scores were higher than those in other groups within the general population, and the estimated prevalence of emotional disturbance was 31.2%, a proportion similar to that reported in medical students in the United States. There were no differences in prevalence or in mean scores of stress between the sexes. Twelve (4%) students reported high intake of alcohol, and almost half of the students had increased their intake in the past two years. The four categories most commonly cited in answers to an open ended question on recent stressful events were talking to psychiatric patients, effects on personal life, presenting cases, and dealing with death and suffering. Relationships with consultants raised the strongest negative feelings, with 102 (34%) students finding these particularly stressful. Stress among medical students should be acknowledged and attempts made to alleviate it.

Alcohol Drinking↗
PubMed1986

What stresses health professionals? A coding system for their answers.

The reliabilities of a coding system derived from open-ended descriptions of stresses and of satisfactions within the medical role are reported as acceptable. The method is considered useful where defences may be raised by direct questioning, and at times of transition where questionnaires derived from previous literature may miss new sources of stress.

Career Choice↗
PubMed1986

The case of the anxious executive: a study from the research clinic.

Most psychotherapists are neither active researchers nor consumers of research findings. Research approaches are needed which build a bridge between clinical realism and independent evidence, but which are applicable in National Health Service settings by clinicians lacking substantial research resources. A new method of clinical inquiry is described which combines measurement techniques developed in psychotherapy research with the therapist's session notes and client perceptions of helpful events in therapy. The method is illustrated by a case study which examines the content of helpful and unhelpful therapy sessions.

Adult↗
PubMed1984

Routine colonoscopy service.

We report our experience of 50 paediatric colonoscopies in a relatively unselected group of patients. Collaboration between an experienced colonoscopist and a paediatrician has provided a smooth, routine service and the examination has proved extremely useful for the diagnosis and management of children with colonic symptoms.

Child↗
PubMed1982

Attributions and recovery from depression: a preliminary study using cross-lagged correlation analysis.

Cross-lagged correlation analysis was employed to test the hypothesis that attributions for symptoms and life-events would exercise a causal influence on the recovery of depressed patients. Patients rated their symptoms and their three most upsetting recent life-events on the dimensions of internality, stability, globality and uncontrollability. These ratings were significantly more global and uncontrollable than those of controls. Among female depressed patients the dimensions of stability and uncontrollability appeared in addition to play a causal role in determining level of depression six weeks later.

Adult↗
PubMed1979

Civil commitment practices in 1977: troubled semantics and/or troubled psychiatry.

This paper examines the practice of involuntary mental hospitalization through examination of criteria used for committment in a sample of 200 civil commitment certificates. Special reference is made, following previous research, to criteria used to describe the person deemed dangerous to himself or to others. The relevance of the findings of present practices in mental health is discussed. New procedures which facilitate presentation of factual evidence, and which eliminate gratuitous information, are required without delay.

Commitment of Persons with Psychiatric Disorders↗
PubMedDate not supplied

Distinct patterns of microvascular endothelial cell morphology are determined by extracellular matrix composition.

Endothelial interactions with the extracellular matrix (ECM) play important roles in angiogenesis but whether specific ECM signals can determine specific cellular morphologies is unclear. The authors compared in vitro ECM-induced morphological responses of the phenotypically distinct human placental microvascular endothelial cells (HPMECs) with large vessel endothelial cells (HUVECs). HPMECs showed distinct patterns of reorganization in response to collagen-I or collagen-IV (monolayer disruption, sprouting, migration) and Matrigel or laminin-A (intussusception, cord formation, tubulogenesis), and an intermediate response to fibrin; whereas HUVECs responded similarly to collagen-1 and Matrigel (elongation, lattice formation, vacuolation) and showed little response to fibrin. Although the extent of collagen and Matrigel responses of HPMECs were increased by serum, acidic or basic fibroblast growth factor (aFGF, bFGF), or vascular endothelial growth factor (VEGF), and varied with matrix protein concentration, the basic patterns were matrix specific, and were independent of fibronectin. The collagen responses correlated with disruption of adherens and tight junctions and the formation of filopodial protrusions. Matrigel responses were associated with up-regulated junctional localization of VE-cadherin, and tubulogenesis developed mainly through paracellular remodeling rather than intracellular vacuolation. Overall, these findings suggest that distinct ECM interactions stimulate specific morphological responses. These signals may regulate morphological behaviour in the angiogenesis cycle, switching endothelial cells between migratory and vasculogenic phenotypes.

Antigens, CD↗