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Biomedical subjects

G Watt

Publications and source records attributed to G Watt.

At least 127 records · Page 7Linked to original sources

Lymphocyte glucocorticoid receptors in asthmatic and control subjects.

Glucocorticoid hormones, which are widely used in the treatment of asthma, have been shown to potentiate physiological and biochemical beta-adrenergic responsiveness in asthmatics. These effects are presumably mediated through glucocorticoid receptors. In order to better understand glucocorticoid pharmacology in asthmatics, we assayed glucocorticoid receptors by directly binding a radioactively labelled glucocorticoid hormone, dexamethasone, to intact lymphocytes prepared from the peripheral blood of asthmatics and control subjects. Binding studies were performed with dexamethasone at 100 nM and 5 nM concentrations. At 100 nM dexamethasone, the mean number of lymphocyte glucocorticoid receptors (per cell) in control subjects (7191 +/- 385, n = 9) was not significantly different from that in asthmatic subjects (7772 +/- 437, n = 9). At 5 nM dexamethasone, the mean number of glucocorticoid receptors in control subjects (1177 +/- 194, n = 5) was not significantly different from that in asthmatic subjects (1215 +/- 108, n = 8). At 100 nM dexamethasone, males had significantly more receptors (7939 +/- 360, n = 11) than females (6764 +/- 72, n = 7). Our results suggest that the number of lymphocyte glucocorticoid receptors and the apparent affinity of dexamethasone for receptors are not related to the presence of severity of asthma; however, a significant sex effect exists which should be corrected for in future studies of lymphocyte glucocorticoid receptors.

Adolescent↗

Treatment of malaria.

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Exchange Transfusion, Whole Blood↗

Decreased mononuclear cell beta-adrenergic receptors in bronchial asthma: parallel studies of lymphocyte and granulocyte desensitization.

To assess the interaction of bronchial asthma and beta-agonist drugs, beta-adrenergic receptors were measured in human mixed leukocyte, mononuclear cell, and polymorphonuclear leukocyte cell membranes simultaneously. The densities and affinities of beta-adrenergic receptors were determined, by Scatchard analysis, with a potent beta-antagonist 125I-hydroxybenzylpindolol (125I-HYP) and compared among 12 nonatopic controls (group I), 13 mild asthmatics not taking drugs (group II), and eight asthmatics receiving long-term beta-agonist therapy (group III). Our findings were as follows. (1) Asthmatics not taking drugs (group II) have significantly lower mean mononuclear leukocyte beta-adrenergic receptor density (p less than 0.05) but no significant difference in mean polymorphonuclear leukocyte beta-adrenergic receptor density than the control group. (2) Asthmatics receiving long-term beta-agonist treatment (group III) had significantly lower mean beta-adrenergic receptor density in all three cell fractions (p less than 0.05). (3) Group I and II females had a higher mean beta-adrenergic receptor density in mixed leukocyte and polymorphonuclear cell fractions than males (p less than 0.05). (4) Terbutaline sulfate clearly caused desensitization of beta-adrenergic receptors in human leukocyte membranes in vivo. These results show that beta-adrenergic receptor density is influenced by cell type, beta-adrenergic agonist administration, and sex; they also show that bronchial asthma itself is associated with lower lymphocyte beta-receptor density.

Administration, Oral↗

Effect of moderate dietary sodium restriction on patients with mild hypertension in general practice.

Eighteen patients with mild hypertension in general practice restricted their sodium intake for eight weeks while taking part in a double-blind randomized crossover trial of sodium and placebo tablets. There was no difference in blood pressure between the two periods of the trial despite a substantial difference in sodium intake. Sodium restriction is not indicated in the management of patients with this degree of hypertension.

Blood Pressure↗

Problems in caring for the elderly mentally infirm at home.

The supporters of psychogeriatric patients attending 5-day hospitals were asked to complete questionnaires concerning the particular problems they experienced in caring for their patients at home. The information provided by the supporter was then related to measures of mood, self-reported strain, and outcome 12 mth from the patients' first attendance. The results pointed to the importance of problems reflecting attentional and emotional demand from such patients, in determining the level of strain, and the supporters' capacity to continue to care for the patient in the community.

Aged↗

Blood pressure reduction in elderly: a randomised controlled trial of methyldopa.

A total of 123 out of 549 elderly residents of local authority welfare homes in Nottinghamshire were found at screening to have a standing or lying diastolic blood pressure of 100 mm Hg or more. These 123 subjects were randomly allocated to simple observation or to treatment with methyldopa. The cumulative mortality was similar in the observed and treated groups and in the normotensive group from which the subjects had been separated. Thus moderate hypertension, whether treated or not, was not a major risk predictor in the elderly population studied.

Aged↗

Air filtration.

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Air Microbiology↗

Comparison of Tensilon and antivenom for the treatment of cobra-bite paralysis.

We prospectively compared the ability of anti-venom and edrophonium (Tensilon) to improve paralytic symptoms in 8 patients envenomed by the Philippine cobra (Naja naja philippinensis). Twenty, 50 or 100 ml of Philippine cobra antivenom were administered in a double-blind fashion by constant intravenous infusion over 30 min. Even the largest dose of antivenom failed to produce marked improvement within 2 h, though enzyme-linked immunosorbent assays and neutralization tests demonstrated that it possessed high titres of anti-neurotoxin antibodies. Tensilon given at 2 h was significantly more effective than antivenom at increasing the duration of upward gaze (78 +/- 28 vs 43 +/- 26 sec, P less than 0.001), and either completely reversed or markedly decreased paralysis in every patient. The Tensilon test should be given to all patients with paralytic envenoming by cobras, and anticholinesterases administered to those with a positive response.

Adolescent↗

Reversal of drug-resistant falciparum malaria by calcium antagonists: potential for host cell toxicity.

Agents capable of reversing multidrug resistance (mdr) in falciparum malaria were investigated for potentiation of chloroquine accumulation and toxicity in a cell culture system. Verapamil, its analog RO11-2933, and desipramine caused a dose-dependent increase in the accumulation of chloroquine (CQ) within human and mouse hepatocytes but not human lung cells. Only those cells in which drug accumulation was enhanced by reversing agents reacted positively for P-glycoprotein (PgP)--the putative mediator of the enhanced drug efflux characteristic of mdr. Clinically achievable concentrations of verapamil (0.4 microM) and desipramine (1 microM) increased CQ accumulation within primary mouse hepatocytes by more than 50%. A well-differentiated normal human cell line (Hep-G2) was killed in media containing a combination of supraphysiological concentrations of CQ and verapamil but survived the same concentrations of either drug alone. Reversing agents may block PgP-mediated drug export from normal tissues as well as from MDR cells. Iatrogenic toxicity resulting from this accumulation of potentially toxic drugs such as CQ within normal cells could complicate the reversal of mdr in vivo.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

The effects of multiplication and synchronicity on the vascular distribution of parasites in falciparum malaria.

The sequestration of erythrocytes containing mature forms of Plasmodium falciparum in the microvasculature of vital organs may cause large discrepancies between the peripheral blood parasite count and the total body parasite burden in falciparum malaria. Despite this, parasitaemia is widely used as an indicator of prognosis and response to treatment. A simple mathematical model describing the changes in circulating and sequestered parasite numbers during acute falciparum malaria is presented. The model uses two parameters only; the standard deviation (SD) of parasite age since merogony (schizogony) as as a measure of synchronicity, and a multiplication factor each 48 h asexual life cycle. The model predicts that during the rising phase of the infection the ratio of circulating to sequestered parasites is dependent largely on the synchronicity of infection rather than multiplication rate, and that in synchronous infections parasitaemias will show considerable fluctuation when the mean stage of parasite development is in the second half of the asexual life cycle. The model fitted well to serial parasite counts from 4 patients with acute uncomplicated falciparum malaria whose infections failed to respond to ciprofloxacin. All four infections were synchronous (SD < or = 4 h), and showed large fluctuations in parasitaemia over short periods related to synchronous sequestration and subsequent reinvasion following merogony. The parasite multiplication rate was determined mainly by the efficiency of merogony or merozoite invasion rather than clearance of circulating parasitized erythrocytes. This suggests that the spleen is relatively inactive during the rising phase of the infection. Quinine treatment did not prevent sequestration but did stop subsequent multiplication.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Prognostic significance of rises in parasitaemia during treatment of falciparum malaria.

Transient rises in parasitaemia occur commonly during the treatment of falciparum malaria but their prognostic significance has not been well defined. Twelve-hourly parasite counts from 133 malaria patients who were ultimately cured were therefore compared with counts from 97 therapeutic failures to determine if increase in parasitaemia was a useful early indicator of poor treatment response. Parasitaemia in both groups frequently rose during the initial 12 h of therapy (41% of all patients), but rising counts thereafter were rarer in treatment successes (P < 0.01). The relative risk of treatment failure was 3.8 if the count was higher at 24 h than 12 h, rose to 7.8 for increases at 48-60 h, and was 13.7 and 19.4 for counts above admission levels at 48 h and 60 h. These data suggest a way to identify patients at high risk of treatment failure.

Antimalarials↗