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Biomedical subjects

M Dawes

Publications and source records attributed to M Dawes.

At least 19 recordsLinked to original sources
PubMed2002

Tumour thickness as a predictor of occult lymph node metastases in patients with stage I and II melanoma undergoing sentinel lymph node biopsy.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is a minimally invasive procedure used accurately to stage nodal basins at risk of occult metastases. There are no data as yet to show a survival benefit from SLNB and its use remains controversial. If Breslow thickness of the tumour correlates well with positive SLNB, it could be used to select patients for SLNB. METHODS: A quantitative systematic review of published studies on SLNB in patients with melanoma available by September 2001 was performed. RESULTS: Twelve studies containing 4218 patients with stage I and II melanoma were identified; 17.8 (95 per cent confidence interval 16.7 to 19.0) per cent of patients had nodal micrometastases detected by SLNB. The incidence of micrometastasis in sentinel nodes correlated directly with Breslow tumour thickness; it was 1.0 per cent for lesions of less than or equal to 0.75 mm, 8.3 per cent for 0.76-1.50 mm, 22.7 per cent for 1.51-4.0 mm and 35.5 per cent for more than 4.0 mm. CONCLUSION: The Breslow thickness of primary melanoma predicts the presence of a sentinel node metastasis. The published data are not sufficient to demonstrate a correlation between other known prognostic indicators and a positive SLNB.

Humans↗
PubMed2002

Management of regional lymph nodes in patients with malignant melanoma: questionnaire survey of UK current practice.

In 2001, a short postal questionnaire regarding the management of regional lymph nodes in patients with cutaneous malignant melanoma was sent to 69 NHS departments of plastic and reconstructive surgery in the UK. Questionnaires were returned by 53 units, giving a response rate of 76.8%. Of these 53 units, 49 reported that they treat patients with primary malignant melanoma. There was considerable variation in the number of melanoma patients managed by each unit. This survey confirmed that elective lymph-node dissection is not routinely practiced in the UK; observation and therapeutic lymph-node dissection for patients who develop regional metastasis is the preferred pattern of care. The majority of centres in the UK do not use sentinel lymph node mapping: only 15 of the 49 units do so (30.6%). The number of sentinel lymph node biopsies performed in each unit varied significantly. There was considerable variation in the materials used and the process of care for sentinel lymph node biopsy. On the basis of this current practice, we recommend the setting up of a prospective clinical melanoma register to record the surgical treatment of melanoma patients.

Humans↗
PubMed2001

Quantitative aspects of the inhibition by N(G)-monomethyl-L-arginine of responses to endothelium-dependent vasodilators in human forearm vasculature.

1. N(G)-monomethyl-L-arginine (L-NMMA) constricts human forearm resistance vasculature and selectively attenuates vasodilator responses to endothelium-dependent vasodilators. Incomplete inhibition of such responses could be due to an inadequate dose of L-NMMA or to NO-independent vasodilator mechanisms. 2. This study sought to determine doses of L-NMMA that are maximally effective in reducing basal and stimulated forearm blood flow. Drugs were infused via the brachial artery in 32 healthy men. Acetylcholine (11 - 330 nmol min(-1)) was compared with albuterol (0.33 - 10 nmol min(-1)), and nitroprusside (1.7 - 20 nmol min(-1)). 3. The effect of L-NMMA on basal flow approached maximum (53+/-2% reduction) at a dose of 16 micromol min(-1). L-NMMA (16 micromol min(-1)) did not significantly influence responses to nitroprusside, but antagonized acetylcholine and albuterol (each P<0.001, by repeated measures analysis of variance). 4. Inhibition of acetylcholine by L-NMMA (16 micromol min(-1)) was strongly influenced by acetylcholine dose (73+/-7% inhibition at 11 nmol min(-1), P<0.01; 4+/-11% inhibition at 330 nmol min(-1), P=NS, Student's paired t-test). Significant inhibition of albuterol was observed at all doses. 5. A higher dose of L-NMMA (64 micromol min(-1)) did not significantly inhibit the response to acetylcholine (330 nmol min(-1)). Responses to this dose of acetylcholine were unaffected by a cyclo-oxygenase (COX) inhibitor (indometacin) alone but combined COX and NO inhibition attenuated acetylcholine responses by 42+/-19%, implying that there is a compensatory increase in the contribution of prostaglandins or NO to acetylcholine-induced dilatation when one or other pathway is inhibited.

Acetylcholine↗
PubMed2001

Drugs in pregnancy. Pharmacokinetics in pregnancy.

Pharmacokinetics describes the handling of a drug by the body - how the drug is absorbed, distributed and eliminated and how these processes determine plasma concentrations of the drug. Changes in maternal physiology during pregnancy influence pharmacokinetics, and this may have important sequelae for drug dosing, especially for drugs for which adverse effects occur at concentrations within, or just above, the therapeutic range. For many drugs absorption is decreased and elimination increased, thus tending to reduce plasma concentrations. There are, however, relatively few specific data on pharmacokinetics in pregnancy, compared to the non-gravid state, because of the obvious ethical issues surrounding studies during pregnancy. Most therapeutic guidelines are thus based on observational studies and basic principles.

Biological Availability↗
PubMed1999

Presentation, management and course of angina and suspected angina in primary care.

Previous surveys may have underestimated both prevalence and incidence of ischemic heart disease in general practice. Case identification is difficult, as many patients presenting with chest pain turn out not to have ischemic heart disease, although their outcome is unclear otherwise. In this work we aimed to: (1) estimate prevalence and incidence of angina in one Oxford general practice; (2) describe the processes of assessment, investigation, and management of suspected angina; and (3) describe the 2-year symptomatic and functional outcome of angina patients, compared with patients whose provisional diagnosis of suspected ischemic heart disease (IHD) was not subsequently sustained (NCCP). A retrospective survey of patients was undertaken (aged 45-74 years) by hand searching paper and electronic medical records to find, as of 1 January 1992, all patients in the practice with continuing treatment of angina diagnosed before 1989, or those having a new diagnosis of angina being assessed (suspected angina) in the 3 year 1989-1991. Two years later, a postal questionnaire survey compared the symptomatic and functional outcome of confirmed IHD and NCCP. On 1 January 1992, the diagnosis of angina was recorded in the notes of 11.1% of patients aged 45-74 years, and the diagnosis was considered correct in 7.4%. Over a 3-year period, 129 people was suspected of suffering from angina, but in 71 (55%) the diagnosis was not confirmed; 76 (59%) were either referred to a specialist out-patient clinic or had an emergency admission. A 2-year follow-up found that similar proportions of patients with angina and noncardiac chest pain had a poor outcome in terms of symptoms, mental state, quality of everyday life, and continuing consultation. The clinical burden of ischemic heart disease in general practice has been underestimated by earlier methodological approaches using less complete ascertainment strategies. The adequacy of current diagnostic and management arrangements for patients with suspected angina merits review, at both the primary and secondary care levels.

Aged↗
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↗