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Biomedical subjects

A Fletcher

Publications and source records attributed to A Fletcher.

At least 19 recordsLinked to original sources
PubMed1992

Quality of life measures in health care. I: Applications and issues in assessment.

Many clinicians remain unsure of the relevance of measuring quality of life to their clinical practice. In health economics quality of life measures have become the standard means of assessing the results of health care interventions and, more controversially, the means of prioritising funding; but they have many other applications. This article--the first of three on measuring quality of life--reviews the instruments available and their application in screening programmes, audit, health care research, and clinical trials. Using the appropriate instrument is essential if outcome measures are to be valid and clinically meaningful.

Clinical Protocols↗
PubMed1992

Behavioural studies on WAY100289, a novel 5-HT3 receptor antagonist, in two animal models of anxiety.

The novel 5-HT3 receptor antagonist, WAY100289, was examined in two animal models of anxiety: the mouse two-compartment light: dark box, and the rat potentiated acoustic startle paradigm. The activity of WAY100289 in the light: dark box model was also compared with that of the selective 5-HT3 receptor antagonists ondansetron, zacopride, ICS-205,930 and quaternary ICS-205,930 (QICS). WAY100289 mimicked the activity profile of benzodiazepine positive controls in the mouse light: dark box, i.e. WAY100289 markedly and significantly increased the exploratory activity of mice in the more aversive light compartment, at doses of 0.01-1.0 mg/kg s.c. and 0.1-10.0 mg/kg p.o. Zacopride and ondansetron induced comparable effects at doses of 0.001-1.0 mg/kg s.c. ICS-205,930 displayed a markedly biphasic dose-response relationship; being active at 0.01 mg/kg s.c., but not at higher or lower doses. QICS was not active in the light: dark box up to a dose of 10 mg/kg s.c., suggesting that the compound does not enter the brain readily. WAY100289 was also active in the rat potentiated acoustic startle model, significantly attenuating the potentiated startle response at doses of 0.03 and 0.3 mg/kg s.c. The activity profile of WAY100289 in this model resembled that of ondansetron. These data strongly suggest that WAY100289 may possess anxiolytic properties in the clinic.

Analysis of Variance↗
PubMed1992

Demonstration of the distribution of coxsackie virus RNA in neonatal mice by non-isotopic in situ hybridization.

A simple method for the demonstration of Coxsackie virus RNA by in situ hybridization is described. Oligonucleotides complimentary to conserved sequences of Coxsackie B genome were synthesised and labelled with digoxigenin using commercially available reagents. In addition to detecting all five Coxsackie B strains examined, six strains of Coxsackie A were also demonstrated by these probes. Using one of the oligonucleotides separately it was possible to distinguish Coxsackie A strains from the strains of Coxsackie B virus examined. This study demonstrates the presence of viral RNA in mice tissues showing morphological evidence of damage, confirming the suspected tropisms of these viruses. The method described is directly applicable to the study of the presence of these viruses in human tissue from diseases where a viral aetiology is suspected.

Animals↗
PubMed1992

Syst-Eur--a multicenter trial on the treatment of isolated systolic hypertension in the elderly: first interim report.

Syst-Eur is a multicenter placebo-controlled outcome trial designed by the European Working Party on High Blood Pressure in the Elderly to investigate the effect of antihypertensive treatment on the incidence of stroke in elderly patients with isolated systolic hypertension (ISH). Eligible patients must be at least 60 years old and have a systolic blood pressure averaging 160-219 mm Hg with a diastolic blood pressure less than 95 mm Hg. The present paper is an interim report on the first 316 patients randomized into this trial. The placebo (n = 170) and active treatment (n = 146) groups were similar at randomization with respect to age (73 +/- 8 years; mean +/- SD), sitting blood pressure (178 +/- 12 mm Hg systolic; 85 +/- 7 mm Hg diastolic), percentage of men (34%), and percentage of patients with cardiovascular complications (29%). After randomization blood pressure fell more (p less than 0.001) in patients on active treatment than in those in the placebo group (19 +/- 20 mm Hg systolic; 6 +/- 10 mm Hg diastolic vs. 7 +/- 19 and 1 +/- 10 mm Hg for sitting blood pressure). This first interim report on the Syst-Eur trial demonstrates that a multinational trial in elderly patients with ISH is feasible and that a significant blood pressure difference between the two treatment groups can be achieved and maintained. New centers are being recruited in order to randomize a total of 3,000 patients.

Aged↗
PubMed1992

Epidermal cytokeratin and immunocyte responses during treatment of psoriasis with calcipotriol and betamethasone valerate.

Changes in epidermal immunocytes and cytokeratins were investigated during treatment of psoriasis with calcipotriol and betamethasone valerate. Skin biopsies were obtained from 10 subjects on each treatment from lesional and non-lesional skin at baseline, and from treated lesions after 4 weeks. In each subject, changes in expression of cytokeratins K5, K10 and K16, and changes in epidermal immunocyte counts were assessed. Responses were compared with a separate histological parameter of improvement, epidermal thickness. Both treatments produced a marked normalization of cytokeratins. The reduction of K16 expression was similar on each treatment and correlated significantly with reduction in epidermal thickness. Expression of both K5 and K10 improved less than thickness with betamethasone valerate but more than thickness with calcipotriol, although these differences did not reach statistical significance. With calcipotriol there was an increase in K5 and K10 responses with increasing response of epidermal thickness, which was not seen with betamethasone valerate. T6+ cells, HLA-DR+ dendritic cells and T lymphocytes were all reduced by betamethasone valerate. There was a remarkable similarity in the level of normalization between cell types and also between cellular response and reduction in thickness. Calcipotriol produced a similar consistent reduction in cell numbers and in thickness, with the exception of T6+ cells which increased in some subjects during treatment. Only in subjects in whom thickness had virtually returned to normal was there a marked decrease in T6+ cells.

Adult↗
PubMed1992

Is poor prognosis really related to HLA-DR expression by malignant melanoma cells?

HLA-DR expression was examined in 50 consecutive primary cutaneous malignant melanomas with a Breslow depth greater than 2 mm using two well-characterized monoclonal antibodies which detect fixation-resistant epitopes. In 31 of these cases (62%) a subpopulation of tumour cells was reactive, although there was considerable heterogeneity. Positive labelling did not correlate with depth but was associated with a reduced likelihood of developing early metastatic disease and a tendency for better overall survival, particularly in male patients. These findings contrast with earlier studies using cryostat sections and one study on paraffin-embedded tissue in which HLA-DR expression was shown to be a poor prognostic factor, but are consistent with the findings in other malignant tumours studied. The significance of HLA-DR expression as a marker of prognosis may depend on the type of tissue preparation, the sensitivity of the immunocytochemical techniques used and the method of assessment.

Female↗
PubMed1992

Quality of life in the treatment of hypertension. The effect of calcium antagonists.

The effects of calcium antagonists on psychological well-being, cognitive function, activity and physical symptoms in hypertensive patients are reviewed. Effects on these aspects of quality of life appear to differ according to whether a dihydropyridine calcium antagonist such as nifedipine is employed or verapamil, which is a phenylalkylamine derivative. Nifedipine has been associated with a self-assessment of impaired cognitive function in 2 clinical trials. Nifedipine was also associated with more symptomatic complaints than both atenolol and verapamil in different studies. The problems with nifedipine centred on oedema, flushing and palpitations. Verapamil was associated with constipation. Compared with other classes of antihypertensive drugs, the position of calcium antagonists with respect to the maintenance of patients' quality of life is presently unclear. Verapamil has been associated with improved quality of life compared with propranolol (a beta-blocker) and nifedipine. Verapamil appears to have similar effects on quality of life as atenolol and the angiotensin converting enzyme (ACE) inhibitor, captopril. The position of nifedipine remains unclear.

Calcium Channel Blockers↗
PubMed1992

New monoclonal antibodies in CD59: use for the analysis of peripheral blood cells from paroxysmal nocturnal haemoglobinuria (PNH) patients and for the quantitation of CD59 on normal and decay accelerating factor (DAF)-deficient erythrocytes.

CD59 is a widely expressed cell surface glycosylphosphatidylinositol (GPI)-linked glycoprotein which acts as an inhibitor of the assembly of the membrane attack complex of autologous complement. Four new monoclonal antibodies to CD59 (2/24, 1B2, BRIC 229, BRIC 257) are described. Competitive binding experiments using these antibodies, two known CD59 antibodies (MEM-43, YTH 53.1) and a previously described antibody LICR-LON-Fib75.1 demonstrated that all seven antibodies see related epitopes on human erythrocyte CD59. In common with other GPI-linked proteins, CD59 (as defined by antibody 2/24) was sensitive to treatment with phosphatidylinositol-specific phospholipase C (PI-PLC) on lymphocytes and monocytes but not on erythrocytes. Flow cytometric analysis using antibody 2/24 identified two populations (CD59 positive and CD59 deficient) of lymphocytes, monocytes and erythrocytes in peripheral blood from a patient with paroxysmal nocturnal haemoglobinuria (PNH). The abundance of CD59 on normal erythrocytes was determined as 21,000 copies/cell when radioiodinated BRIC 229 was used. Other CD59 antibodies gave values of 10,000 (IF5) and 15,000 (2/24) against the same target cells. Radioiodinated Fab fragments of BRIC 229 gave a value of 39,000 copies/cell. Erythrocytes from two individuals with a rare inherited deficiency of decay accelerating factor (DAF), known as the Inab phenotype, expressed normal levels of CD59.

Antibodies, Monoclonal↗
PubMed1992

[SYST-EUR: a multicenter trial of treatment of systolic hypertension in aged subjects. An initial report].

Syst-Eur is a multicentre placebo-controlled outcome trial, designed by the European Working Party on High Blood Pressure in the Elderly (EWPHE), to investigate the effect of antihypertensive treatment on the incidence of stroke in elderly patients with isolated systolic hypertension (ISH). Eligible patients must be at least 60 years old and have a systolic blood pressure averaging 160-219 mmHg with a diastolic blood pressure less than 95 mmHg. The present paper in an interim report on the first 316 patients randomized into this trial. The placebo (N = 170) and active treatment (N = 146) groups were similar at randomization with respect to age (73 +/- 8 years; mean +/- standard deviation), sitting blood pressure (178 +/- 12/85 +/- 7 mmHg), percentage men (34%) and percentage of patients with cardiovascular complications (29%). After randomization blood pressure fell more (p < 0.001) on active treatment than in the placebo group (19 +/- 20/6 +/- 10 mmHg versus 7 +/- 19/1 +/- 10 mmHg for the sitting blood pressure). This first interim report on the Syst-Eur trial demonstrates that a multinational trial in elderly patients with ISH is feasible and that a significant blood pressure difference between the 2 treatment groups can be achieved and maintained. New centres are being recruited in order to randomize a total of 3,000 patients.

Aged↗
PubMed1992

Quality of life and antihypertensive drugs in the elderly.

Hypertension is common in the elderly with estimates of around 10-20% showing a sustained level of pressure, either systolic (greater than or equal to 160 mmHg), or diastolic (greater than or equal to 90 mmHg) or both. The benefits of treating subjects with raised diastolic pressure was shown by the trials of the European Working Party on High Blood Pressure in the Elderly (EWPHE), the Hypertension in Elderly Patients in Primary Care (HEP), and the Swedish Trial in Old patients with Hypertension (STOP-Hypertension). Evidence for the benefit of treating isolated systolic hypertension in the elderly was provided in one trial (SHEP: Systolic Hypertension in the Elderly Program), and the results of two others are awaited. However, it is important to provide data on all treatment effects, including adverse reactions as well as benefits. In addition to traditional measures of mortality, morbidity and side effects, the quality of life in patients on antihypertensive treatment should be considered. The methods of measuring quality of life in trials is discussed, and some results presented.

Aged↗
PubMed1990

Exposure to high pressure may produce the 5-HT behavioral syndrome in rats.

In addition to the motor events associated with high pressure neurologic syndrome (HPNS), we have observed behavioral changes that resemble the 5-hydroxytryptamine (5-HT) syndrome in free-moving rats exposed to pressures up to 70 ATA. These include a flat body posture, head weaving, reciprocal forepaw treading, and hyperlocomotion. Such changes occur when brain 5-HT levels are raised or when 5-HT receptors are activated. We have therefore studied the behavior of rats at pressure treated either with saline or with one of the following drugs: p-chlorophenylalanine (pCPA) which depletes brain 5-HT by 85-90%, Wy 27587 which inhibits 5-HT reuptake, 5-hydroxytryptophan (5-HTP) and carbidopa which increase brain 5-HT synthesis, and quipazine which is a 5-HT receptor-agonist. After treatment, rats were individually exposed to pressure, and behavioral scores were made for 5 min every 10 ATA up to 70 ATA by an unbiased observer who was not aware of the treatment given. Analysis of all control rats indicated that only a flat body posture, forepaw treading, and hyperlocomotion were positively correlated with pressure, and these events were used in all subsequent analysis. Rats treated with pCPA with whole brain 5-HT levels reduced by 90% had scores significantly less than controls. Rats treated with Wy 27587 showed significantly increased scores. Rats treated with 5-HTP and quipazine failed to show a significant increase in scores. These results suggest that a modified form of the 5-HT syndrome occurs when rats are exposed to increased pressure, and the behavioral events seen are consistent with some activation of the 5-HT1A receptor subtype.

5-Hydroxytryptophan↗
PubMed1977

Fibrin and fibrinogen proteolysis products: comparison between gel filtration and SDS polyacrylamide electrophoresis analysis.

The proteolysis of purified human fibrinogen, stabilized and non-stabilized fibrin by plasmin were investigated by gel filtration analysis and SDS polyacrylamide electrophoresis of the reaction products. Plasmin proteolysis of fibrinogen followed the sequential steps previously reported and the two analytical methods yielded concordant results. Large molecular weight proteolysis products, of substantially greater molecular weight than native fibrinogen, were identified by gel filtration analysis following dissolution of stabilized and non-stabilized fibrin clots; with further incubation with plasmin, these proteolysis products gradually diminished in size. On the other hand, SDS polyacrylamide electrophoresis of these fibrin digests demonstrated that while non-stabilized fibrin yielded breakdown products similar in size to those obtained after proteolysis of fibrinogen, stabilized fibrin digests showed moieties of greater molecular size estimated to be of molecular weight 400,000 to 800,000. The final breakdown products of stabilized fibrin differed from those of fibrinogen and nonstabilized fibrin in that fragment D was present in the "double D" cross-linked form.

Antigens↗
PubMed1976

Hemostatic alterations accompanying sickle cell pain crises.

Three patients with sickle-cell disease (SSD) were followed, weekly, for 1 1/2 to 2 years, during which time they experienced one or more episodes of crisis. Crisis was associated with reproducible sequential hemostatic alterations indicating intravascular fibrin formation and a marked disturbance in platelet economy. With crisis onset, or possibly before, there was an increase in plasma high-molecular-weight fibrinogen complexes and a transient fall in platelet count, with a subsequent rise in both fibrinogen concentration and platelet count; plasma fibrinogen peaked 1 week after crisis onset and platelet count approximately 2 weeks after onset. Subsidence of crisis was associated with a fall in high-molecular-weight fibrinogen complexes and a subsequent increase in fibrinogen first derivative, an early fibrinogen breakdown product. Hemostatic findings and patient clinical status were generally correlated, the findings during asymptomatic periods being essentially normal. Agents affecting platelet function (aspirin alone or in combination with dipyridamole) appeared to reduce the extent of laboratory abnormality, suggesting potential clinical usefulness in this disorder.

Acute Disease↗