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Biomedical subjects

M Dawes

Publications and source records attributed to M Dawes.

29 records · Page 2Linked to original sources
PubMed1999

Etiology of early age onset substance use disorder: a maturational perspective.

The etiology of early age onset substance use disorder (SUD), an Axis I psychiatric illness, is examined from the perspective of the multifactorial model of complex disorders. Beginning at conception, genetic and environment interactions produce a sequence of biobehavioral phenotypes during development which bias the ontogenetic pathway toward SUD. One pathway to SUD is theorized to emanate from a deviation in somatic and neurological maturation, which, in the context of adverse environments, predisposes to affective and behavioral dysregulation as the cardinal SUD liability-contributing phenotype. Dysregulation progresses via epigenesis from difficult temperament in infancy to conduct problems in childhood to substance use by early adolescence and to severe SUD by young adulthood.

Adolescent↗
PubMed1999

The vasodilator action of nebivolol in forearm vasculature of subjects with essential hypertension.

AIMS: Brachial artery administration of nebivolol increases forearm blood flow in normotensive subjects through activation of the L-arginine/NO pathway. The aim of the present study was to investigate the effect of brachial artery administration of nebivolol in subjects with essential hypertension. METHODS: We studied eight patients with uncomplicated essential hypertension and serum cholesterol less than 6.9 mmol l-1. Antihypertensive medication was discontinued 2 weeks before the study in previously treated patients. Following cannulation of the left brachial artery, saline was infused to establish baseline blood flow, followed by increasing doses of nebivolol (88.5, 177 and 354 microg min-1, each dose for 6 min), followed by saline for 12 min, followed by a 30 min infusion of L-NMMA (2 mg min-1 ). During the final 18 min of the L-NMMA infusion, nebivolol was coinfused using the same doses as before. Forearm blood flow was measured in both arms using venous occlusion plethysmography. RESULTS: Blood flow in the noninfused arm did not change significantly throughout the study. In the infused arm blood flow increased significantly in a dose-related manner during the first series of nebivolol infusions from 2.76+/-0.39 ml min-1-1 100 ml forearm-1 during the baseline period to 4.40+/-0.60 ml min-1-1 100 ml forearm-1 (mean+/-s.e. mean, n=8, P=0.0003 by anova ). L-NMMA antagonized the vasodilator effect of nebivolol: baseline blood flow in the infused arm was 2.41+/-0.53 ml min-1 100 ml forearm-1 and 2.94+/-0.42 ml min-1 100 ml forearm-1 during coinfusion of the top dose of nebivolol with L-NMMA (P=0.0006 for an effect of L-NMMA on nebivolol response). There were no serious adverse events. CONCLUSIONS: Nebivolol causes vasodilation in the forearm vascular bed in subjects with essential hypertension. Since this response is antagonized by L-NMMA, the vasodilatation is probably caused by activation of the L-arg/NO pathway.

Adolescent↗
PubMed1999

Family and peer correlates of behavioral self-regulation in boys at risk for substance abuse.

Behavioral self-regulation (BSR), defined herein as the degree to which one can control one's own activity and reactivity to environmental stimuli, has been posited to be salient to the onset of adolescent substance abuse. The goal of this study was to clarify particular family and peer correlates of BSR in at-risk sons. Subjects were 10-through 12-year-old sons of substance-abusing fathers (high-average risk [HAR]; n = 176) and normal controls (low-average risk [LAR]; n = 199). A BSR latent trait was developed using multiple measures and multiple informants. Analyses included separate hierarchical linear regressions for HAR and LAR groups. In the hierarchical linear model for HAR sons, family dysfunction and deviant peer affiliation were significantly associated with BSR, whereas for LAR sons, only peer affiliation was significantly associated with BSR. The above family and peer correlates differed in proportions of variance explained for BSR in HAR and LAR sons. These findings extend previous studies by showing that, in a hierarchical linear model, BSR in HAR sons is associated with specific interpersonal, family, and peer factors. These findings suggest that empirical, theory-guided interventions to prevent worsening of BSR in HAR boys should address specific interpersonal, family, and peer factors.

Adult↗
PubMed1998

GP frequent consulters: their prevalence, natural history, and contribution to rising workload.

A small proportion of patients use a disproportionate amount of general practitioners' (GPs') time. We demonstrate here that such frequent attending behaviour tends to persist through five-year follow-up, suggesting the need for the development of specific management strategies. We also show that, at any rate in one practice, total workload is increasing dramatically, and that frequent consulters make up a large part of the increase.

Adolescent↗
PubMed1997

Effects of inhibition of the L-arginine/nitric oxide pathway on vasodilation caused by beta-adrenergic agonists in human forearm.

BACKGROUND: We examined whether vasodilator responses to beta-agonists in human forearm vasculature are mediated in part through the nitric oxide pathway. METHODS AND RESULTS: We measured forearm blood flow responses to brachial artery infusions of beta-adrenergic agonists in healthy men. Salbutamol was more than 100 times as potent as dobutamine. Cumulative doses of salbutamol (0.3 to 3.5 nmol.min-1) did not cause tachyphylaxis to an identical repeated infusion after a 24-minute recovery period. Vasodilators were infused with this sequence during coinfusion of saline and NG-monomethyl-L-arginine (L-NMMA, 4 mumol.min-1), an inhibitor of nitric oxide synthase. L-NMMA coinfusion inhibited responses (area under the dose-response curve) to isoproterenol (0.01 to 0.1 nmol.min-1) by 59 +/- 7% (n = 5) and inhibited those to salbutamol (0.3 to 3.5 nmol.min-1) by 52 +/- 6% (n = 8). L-NMMA had no significant effect on vasodilator responses to nitroprusside (2.7 to 11.0 nmol.min-1, n = 8), verapamil (20 to 80 nmol.min-1, n = 8), or prostacyclin (0.08 to 0.24 nmol.min-1, n = 8). CONCLUSIONS: These results suggest that beta-adrenergic vasodilator responses in human forearm vasculature are mediated predominantly through beta 2-adrenergic receptors and are dependent on nitric oxide synthesis.

Adolescent↗
PubMed1996

Day surgery and community health services work load: a descriptive study.

This prospective descriptive study of primary health care workload in the five days after day surgery is based on a questionnaire to patients who received day surgery in a specialist unit in Oxford. Half of all patients received health care, the mean consultation time was 16 minutes, and half the consultations were within two days of surgery.

Ambulatory Surgical Procedures↗
PubMed1994

Within-patient correlation between the antihypertensive effects of atenolol, lisinopril and nifedipine.

OBJECTIVE: To investigate whether there are definable subgroups of patients with essential hypertension who respond specifically to particular antihypertensive drugs. DESIGN: Randomized cross-over comparison of the antihypertensive effect of 50 mg atenolol per day, 10 mg lisinopril per day and 20 mg nifedipine retard twice a day. Ambulatory blood pressure monitoring was used to assess the blood pressure level both for recruitment and at the end of each treatment period. The treatment periods lasted 4 weeks and were preceded by 4 weeks of placebo. PATIENTS: Seventy-two untreated hypertensive patients with a mean age of 52 (SD 8.4) years were recruited from six general practices and from the hospital outpatient clinic. Sixty-eight patients completed the trial. MAIN OUTCOME MEASURES: To assess the within-patient correlations among the blood pressure responses to each drug and explore the possible role of simple characteristics, such as the initial blood pressure, plasma renin concentration and age, in identifying the responders to a particular drug. RESULTS: Systolic/diastolic blood pressure fell significantly with each agent (P < 0.001): atenolol reduced it by 16.3 +/- 13.3/9.9 +/- 8.8, lisinopril by 14.8 +/- 15.0/9.4 +/- 9.1 and nifedipine by 11.6 +/- 12.3/6.7 +/- 8.3 mmHg. There was a low degree of correlation between the changes in blood pressure with the three drugs in individual patients. With each drug there was a small percentage (8.9-14.7%) of non-responders. The initial level of systolic blood pressure was weakly correlated with the antihypertensive effect of nifedipine (r = 0.47, P < 0.001) and plasma renin concentration was related to the effect of atenolol (r = 0.32, P < 0.01). Age did not predict the blood pressure response to any agent. CONCLUSIONS: The low level of the correlation between the blood pressure changes with the three drugs suggests that different mechanisms may be involved in the aetiology of essential hypertension. Plasma renin concentration and the initial level of systolic blood pressure contribute only weakly to the identification of responders to the three drugs.

Adolescent↗
PubMedDate not supplied

Mg(2+)-induced vasodilation in human forearm vasculature is inhibited by N(G)-monomethyl-L-arginine but not by indometacin.

We have investigated the mechanism of the vasodilator action of Mg(2+) in human forearm resistance vasculature. Venous occlusion plethysmography was used to measure vasodilator responses to Mg(2+) infused via the brachial artery in healthy men, and to determine effects on Mg(2+) responses of indometacin (an inhibitor of cyclo-oxygenase) and of N(G)-monomethyl-L-arginine (L-NMMA, an inhibitor of the L-arginine/nitric oxide, L-arg/NO, pathway). Magnesium sulphate infusion (0.05, 0.1, 0.2 mmol x min(-1)) increased plasma Mg(2+) concentration to 1.57+/-0.16 mmol x l(-1) in venous blood from the infused arm at the highest dose. There was a dose-related increase in forearm blood flow in the infused arm to a maximum of 6.37+/-1.37 ml x min(-1) x dl forearm(-1) at the highest dose corresponding to an increase of 159+/-25% in blood flow relative to the non-infused arm. There was no tachyphylaxis during a second infusion following a 21-min recovery period. Indometacin had no effect on vasodilator responses to Mg(2+), whereas L-NMMA inhibited Mg(2+) responses (area under the dose-response curve) by 43+/-6% (p = 0.0003 by repeated-measures ANOVA). Therefore the L-arg/NO pathway is responsible, in part, for the vasodilator action of Mg(2+) in human forearm resistance vasculature.

Adult↗
PubMedDate not supplied

Peaceful means.

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Adaptation, Psychological↗