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Biomedical subjects

A Fletcher

Publications and source records attributed to A Fletcher.

At least 199 records · Page 11Linked to original sources
PubMed1989

Relation between mortality and treated blood pressure in elderly patients with hypertension: report of the European Working Party on High Blood Pressure in the Elderly.

OBJECTIVE: To investigate the relation between mortality and treated systolic and diastolic blood pressures. DESIGN: Randomised double blind placebo controlled trial. Mortality in the two treatment groups was examined in thirds of treated systolic and diastolic blood pressures. PATIENTS: 339 And 352 patients allocated to placebo and active treatment, respectively. The groups were similar at randomisation in sex ratio (70% women), mean age (71.5 years), blood pressure (182/101 mm Hg), and proportion of patients with cardiovascular complications (35%). MEASUREMENTS AND MAIN RESULTS: In the placebo group total mortality rose with increasing systolic pressure whereas it had a U shaped relation with diastolic pressure, the total lowest mortality being in patients in the middle third of the distribution of diastolic pressure. In the group given active treatment total mortality showed a U shaped relation with systolic pressure and an inverse association with treated diastolic pressure. In both groups cardiovascular and non-cardiovascular mortality followed the same trends as total mortality. The increased mortality in the lowest thirds of pressure was not associated with an increased proportion of patients with cardiovascular complications at randomisation or with a fall in diastolic pressure exceeding the median fall in pressure in each group. In contrast, patients in the lowest thirds of pressure showed greater decreases in body weight and haemoglobin concentration than those in the middle and upper thirds of pressure. CONCLUSIONS: In patients taking active treatment total mortality was increased in the lowest thirds of treated systolic and diastolic blood pressures. This increased mortality is not necessarily explained by an exaggerated reduction in pressure induced by drugs as for diastolic pressure a U shaped relation also existed during treatment with placebo. In addition, patients in the lowest thirds of systolic and diastolic pressures were characterised by decreases in body weight and haemoglobin concentration, and the patients in the lowest thirds of diastolic pressure taking active treatment also by an increased non-cardiovascular mortality, suggesting some deterioration of general health.

Aged↗
PubMed1989

Evidence that blockade of post-synaptic 5-HT1 receptors elicits feeding in satiated rats.

The effects of nine central 5-HT antagonists on food intake in free feeding male rats were examined. The 5-HT2 antagonists ritanserin and ketanserin and the selective 5-HT3 antagonists ICS 205-930 and MDL 72222 had no effect on food intake. In contrast, the non-selective 5-HT antagonists metergoline, methiothepin, mesulergine, mianserin and methysergide (all of which have high affinity for various 5-HT1 receptor subtypes), dose-dependently increased food intake during a 4-h daytime test. Furthermore, metergoline dose dependently increased food intake over a 24-h period. Surprisingly, mesulergine decreased food intake over a 24-h period at the same doses that increased daytime food intake. This may indicate that the increase in daytime feeding produced by mesulergine is a non-specific response. Although the antagonists used have varying degrees of selectivity for 5-HT receptor subtypes, the pattern of results suggests that postsynaptic 5-HT1 receptors (possibly of the 5-HT1C type) play an important role in the control of feeding in rats.

Animals↗
PubMed1989

Evidence for a decreased noradrenaline sensitivity in mesenteric resistance vessels from rats with chemical renal medullectomy.

1. Chemical renal medullectomy was performed in Wistar rats by intraperitoneal injection of 2-bromoethylamine hydrobromide (200 mg/kg body weight). The effect of this treatment upon blood pressure and mesenteric vascular reactivity and morphology was studied 3 weeks after treatment. 2. Blood pressure was significantly raised in medullectomized rats. The indirect systolic pressures (means +/- SEM) were 112 +/- 2.4 mmHg (14.9 +/- 0.32 kPa) and 123 +/- 3.5 mmHg (16.4 +/- 0.5 kPa) (P less than 0.02) for control (n = 12) and medullectomized (n = 12) rats, respectively. However, there were no significant changes in the morphology of the mesenteric resistance vessels. 3. Maximum pressor responses and Ca2+ sensitivities were unchanged in these vessels compared with controls, but the sensitivity to noradrenaline was significantly reduced. Noradrenaline pD2 (= -log ED50) values (means +/- SEM) were 5.87 +/- 0.03 and 5.69 +/- 0.08 (P less than 0.05) for control (n = 12) and medullectomized (n = 12) rats, respectively. 4. This study demonstrates that in this model of hypertension the noradrenaline sensitivity is reduced in mesenteric resistance vessels, but there are no detectable morphological changes associated with the rise in blood pressure.

Animals↗
PubMed1989

Joint pain and quality of life; results of a randomised trial.

1. Eight hundred and forty-six patients with pain in one or two joints of the hip, knee, ankle or wrist participated in a randomised double-blind trial to compare the efficacy, tolerability and effect on quality of life of diclofenac sodium slow release (DSR) 100 mg daily and a combination of dextropropoxyphene 180 mg and paracetamol 1.95 g daily (D&P). Health status or quality of life was measured using the Nottingham Health Profile (NHP) questionnaire. 2. Pain as measured by a visual analogue scale (VAS) showed 8% greater pain reduction with DSR as compared with D&P (P less than 0.05). Physical mobility as measured by the NHP improved by 13% more with DSR as compared with D&P (P less than 0.01). Energy, sleep, social isolation and emotional reactions did not differ significantly between the two treatment groups, but both treatment groups showed improvement during the trial. More D&P patients as compared with DSR patients reported problems with their job of work (P less than 0.05), and time lost from work (P less than 0.05). 3. Patients on D&P suffered an excess of tiredness or sleep disturbance (50 vs 21, P less than 0.01) whilst patients treated with DSR had an excess of abdominal or epigastric pain or indigestion (40 vs 18, P less than 0.01). 57 patients were withdrawn from DSR and 65 from D&P.

Acetaminophen↗
PubMed1989

Expression of cytokeratin in the epithelium of dentigerous cysts and odontogenic keratocysts: an aid to diagnosis.

Sections of tissue embedded in paraffin wax from 18 selected odontogenic cysts were studied both histologically and immunohistochemically with antibodies to cytokeratins using the indirect peroxidase technique. The cysts were divided on a clinical and histological basis into two equal groups comprising dentigerous cysts and odontogenic keratocysts. It was possible to differentiate the two cyst types in every case by the pattern of staining using the monoclonal antibody LP34 for cytokeratins of intermediate molecular weight. The monoclonal antibody CAM 5.2 for cytokeratins of low molecular weight was not discriminatory. Such a clear distinction may prove useful diagnostically in distinguishing between two cysts of similar appearance but very different behaviour.

Dentigerous Cyst↗
PubMed1988

Quality of life on angina therapy: a randomised controlled trial of transdermal glyceryl trinitrate against placebo.

In a randomised controlled trial in 427 men with chronic stable angina continuous use of 5 mg transdermal glyceryl trinitrate (GTN) showed no advantage over placebo in terms of efficacy (anginal attack rates and sublingual GTN consumption) or quality of life (as measured with the sickness impact profile and a health index of disability). Patients on the active drug reported headaches more frequently than patients on placebo, and a higher proportion of them withdrew from the trial because of headache. Quality-of-life measurements showed a significant adverse effect of active treatment, principally in the social interaction dimension of the sickness impact profile. A similar effect was observed in placebo patients when crossed to active treatment in a 4-week single-blind period. The results suggest no benefit in the relief of chest pain from 5 mg transdermal GTN when used continuously.

Administration, Cutaneous↗
PubMed1988

A proconvulsant action of selective alpha 2-adrenoceptor antagonists.

The effects of alpha 2-adrenoceptor agonists and antagonists were examined on seizure thresholds determined by intravenous infusions of convulsants in rodents. alpha 2-Adrenoceptor antagonists were proconvulsant; dose dependently reducing the threshold for pentylenetetrazol- or bicuculline-induced tonic seizures. Strychnine-induced tonic seizures were unaffected. The alpha 2-adrenoceptor agonists clonidine, BHT-933 and UK 14,304 did not modify pentylenetetazol-induced seizures at low or moderate doses but at high doses clonidine and BHT-933 were proconvulsant. The facilitatory effect of alpha 2-adrenoceptor antagonists on pentylenetetrazol-induced tonic seizures was blocked by clonidine or UK 14,304. The proconvulsant action of alpha 2-adrenoceptor antagonists was contrasted with that of ethyl-beta-carboline-3-carboxylate, a benzodiazepine receptor contragonist, which markedly reduced the threshold for seizure initiation rather than the tonic seizure threshold. The selective facilitatory action of alpha 2-adrenoceptor blockade on tonic seizures suggests that a noradrenergic mechanism is involved in the control of seizure propagation rather than seizure initiation.

Adrenergic alpha-Agonists↗
PubMed1988

Immunohistochemical staining patterns of sweat glands and their neoplasms using two monoclonal antibodies to keratins.

The staining patterns of normal sweat glands and sweat gland-derived neoplasms using 2 monoclonal antibodies to keratins (Dako-CK1, Cam 5.2) has been assessed. Based on findings in normal glands, the differentiation of these benign neoplasms is considered, with positive evidence for apocrine and eccrine differentiation, and in the latter, differentiation to ductal or secretory type epithelia. This easily applied technique (indirect immunoperoxidase) is suitable for use in routinely processed tissue and employs 2 commercially available monoclonal antibodies. The findings may be of assistance in general surgical reporting of problematic cases.

Adenoma, Sweat Gland↗
PubMed1988

Skeletal muscle expression of class II histocompatibility antigens (HLA-DR) in polymyositis and other muscle disorders with an inflammatory infiltrate.

Muscle biopsy specimens with a pronounced inflammatory component were evaluated for myocyte expression of class II histocompatibility antigens (HLA-DR) by immunohistochemical techniques. All 15 cases of polymyositis were positive; six cases of muscular dystrophy (two Duchenne, four facio-scapulo-humeral), and one case of acute denervation (motor neurone disease) were negative, despite having a comparably intense mononuclear infiltrate. Twelve entirely normal biopsy specimens were also negative for HLA-DR expression. Expression of this membrane glycoprotein may have a clinically important aetiological role in polymyositis, and demonstration of its presence may prove useful as a marker for this disorder in selected problematic biopsy specimens.

HLA-D Antigens↗
PubMed1988

Beta adrenoceptor blockade is associated with increased survival in male but not female hypertensive patients: a report from the DHSS Hypertension Care Computing Project (DHCCP).

The DHCCP is a multicentre observational study of patients being treated for hypertension in the United Kingdom. The influence of the type of anti-hypertensive therapy on survival was examined in 2,697 patients followed from 1971 with 206 deaths up to November 1981. Patients were classified by three types of treatment after one year in the project: betablockers (1,387), methyldopa (452) and others (667), (70% on diuretics only). The data were analysed both for all patients and for a subset excluding patients with previous ischaemic heart disease by all cause and IHD age-adjusted rates and life table analysis. Men on beta blockers had lower rates for total mortality, when compared with men on methyldopa (64% of the methyldopa rate, P less than 0.05) and when compared with men on other treatments (76% of the other treatment rate, P less than 0.1). The results for IHD mortality were similar. This improved survival of men in the beta blocker group was also found in the subset with no prior history of IHD. The benefit of beta blockers was not apparent in women: the lowest rates were observed for women on methyldopa, but the confidence limits for the ratios of relative rates were wide. Adjustment for blood pressure and cigarette smoking using the Cox proportional hazards model did not substantially modify the ratios of the mortality rates for the treatment groups. A sub-group analysis showed the reduction in all cause and IHD mortality associated with beta blockers was mainly due to the effect in non-smoking men.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1988

Diuretics--a risk in the long-term treatment of hypertensive patients?

The trial of the European Working Party on High blood pressure in the Elderly (EWPHE) revealed an overall decrease in cardiovascular mortality and morbidity in the actively treated patients. They received as first-line drugs a combination of hydrochlorothiazide and triamterene; methyldopa was added as necessary. The present post hoc analysis examined the effect of the diuretic treatment on cardiovascular events, both when given alone and in conjunction with methyldopa, by calculating the relative hazard rates (RHR) for cardiovascular mortality and morbidity. Using the Cox proportional hazard model, compared with placebo, a 34% reduction in cardiovascular mortality in the intention-to-treat analysis was demonstrated in the diuretic (hydrochlorothiazide and triamterene) group with an RHR of 0.66 and a 95% confidence interval (CI) of 0.44-0.97; the 16% decrease in the group treated with diuretics and methyldopa was not significant (RHR, 0.84; 95% CI, 0.56-1.25). The effect of treatment in the latter combined group became significant (RHR, 0.62; 95% CI, 0.40-0.95) when all cardiovascular study terminating events were considered; they were reduced by 38%. No effect of treatment on mortality from all causes was detected.

Aged↗
PubMed1987

Blood grouping with monoclonal antibodies.

The Technicon BG15 automated blood grouping machine has been used to type over 32,000 blood donors with a monoclonal anti-A and anti-B. The results of using these antibodies in parallel with conventional human antisera will be presented along with preliminary data obtained with the Groupamatic 2000 using a different anti-A. A monoclonal anti-N reagent has been assessed for its suitability for use as a blood grouping reagent in microplate assays by testing 10,000 blood donors in parallel with Vicia graminea anti-N lectin or rabbit anti-N. There was complete correlation between the results obtained with the monoclonal antibodies and conventional reagents.

Antibodies, Monoclonal↗
PubMed1986

Calcitonin gene-related peptide (CGRP) acts independently of calcitonin on cyclic AMP formation in clonal osteogenic sarcoma cells (UMR 106-01).

In several human cancer cell lines and in a subclone of rat osteogenic sarcoma cells (UMR 106-06) possessing calcitonin receptors and a calcitonin-responsive adenylate cyclase, calcitonin gene-related peptide (CGRP) behaved as a weak calcitonin agonist. In another subclone of the same osteogenic sarcoma (UMR 106-01) with no measurable calcitonin receptors or response, both rat and human CGRP were found to increase cyclic AMP formation in a dose-dependent manner. The data indicate that CGRP is capable of a weak calcitonin-like action in cells with calcitonin receptors, but also that in some cells CGRP activates adenylate cyclase itself, independently of calcitonin receptors.

Animals↗
PubMed1986

Blood grouping with monoclonal anti-N antibodies.

Four monoclonal antibodies (N1, N3, N4 and N5) with specificity for the N blood group have been produced from fusions in which human erythrocytes were used as the immunizing stimulus. N1 and N3 differed from N4 and N5 with regard to their serological specificities and pH optima. Antibody N3 has been assessed for its suitability as a blood grouping reagent by testing 10,767 blood donors in parallel with Vicia graminea anti-N lectin or rabbit anti-N. There was complete correlation between the results obtained with the monoclonal and conventional reagents providing strong evidence that N3 is a reliable and potent blood grouping reagent.

Antibodies, Monoclonal↗