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Biomedical subjects

Simon R J Maxwell

Publications and source records attributed to Simon R J Maxwell.

13 recordsLinked to original sources
PubMed2006

eDrug: a dynamic interactive electronic drug formulary for medical students.

AIMS: Prescribing drugs is a key responsibility of a doctor and requires a solid grounding in the relevant scientific disciplines of pharmacology and therapeutics (PT). The move away from basic science disciplines towards a more system-based and integrated undergraduate curriculum has created difficulties in the delivery of PT teaching in some medical schools. We aimed to develop a web-based strategy to overcome these problems and improve the PT learning experience. METHODS: We designed and introduced 'eDrug', a dynamic interactive web-based student formulary, as an aid to teaching and learning of PT throughout a 5-year integrated medical curriculum in a UK medical school of 1300 students. This was followed by a prospective observational study of student-reported views about its impact on their PT learning experience. RESULTS: eDrug was rated highly by students and staff, with the main benefits being increased visibility of PT in the curriculum, clear identification of core drugs, regular sourcing of drug information via direct links to accredited sources including the British National Formulary, prioritization of learning, immediate access and responsiveness. It has also served as a focus of discussion concerning core PT learning objectives amongst staff and students. CONCLUSIONS: Web-based delivery of PT learning objectives actively supports learning within an integrated curriculum.

Adult↗
PubMed2006

Effects of short-term isocapnic hyperoxia and hypoxia on cardiovascular function.

Both hypoxia and hyperoxia have major effects on cardiovascular function. However, both states affect ventilation and many previous studies have not controlled CO(2) tension. We investigated whether hemodynamic effects previously attributed to modified O(2) tension were still apparent under isocapnic conditions. In eight healthy men, we studied blood pressure (BP), heart rate (HR), cardiac index (CI), systemic vascular resistance index (SVRI) and arterial stiffness (augmentation index, AI) during 1 h of hyperoxia (mean end-tidal O(2) 79.6 +/- 2.0%) or hypoxia (pulse oximeter oxygen saturation 82.6 +/- 0.3%). Hyperoxia increased SVRI (18.9 +/- 1.9%; P < 0.001) and reduced HR (-10.3 +/- 1.0%; P < 0.001), CI (-10.3 +/- 1.7%; P < 0.001), and stroke index (SI) (-7.3 +/- 1.3%; P < 0.001) but had no effect on AI, whereas hypoxia reduced SVRI (-15.2 +/- 1.2%; P < 0.001) and AI (-10.7 +/- 1.1%; P < 0.001) and increased HR (18.2 +/- 1.2%; P < 0.001), CI (20.2 +/- 1.8%; P < 0.001), and pulse pressure (13.2 +/- 2.3%; P = 0.02). The effects of hyperoxia on CI and SVRI, but not the other hemodynamic effects, persisted for up to 1 h after restoration of air breathing. Although increased oxidative stress has been proposed as a cause of the cardiovascular response to altered oxygenation, we found no significant changes in venous antioxidant or 8-iso-prostaglandin F(2alpha) levels. We conclude that both hyperoxia and hypoxia, when present during isocapnia, cause similar changes in cardiovascular function to those described with poikilocapnic conditions.

Adaptation, Physiological↗
PubMed2006

Uric acid restores endothelial function in patients with type 1 diabetes and regular smokers.

Endothelial dysfunction is a characteristic finding in both patients with type 1 diabetes and in regular smokers and is an important precursor to atherosclerosis. The urate molecule has antioxidant properties, which could influence endothelial function. The impact of acutely raising uric acid concentrations on endothelial function was studied in eight men with type 1 diabetes, eight healthy regular smokers, and eight age-matched healthy control subjects in a randomized, four-way, double-blind, placebo-controlled study. Subjects received 1,000 mg uric acid i.v. in vehicle, 1,000 mg vitamin C as a control antioxidant, vehicle alone, or 0.9% saline on separate occasions over 1 h. Forearm blood flow responses to intrabrachial acetylcholine and sodium nitroprusside were assessed using venous occlusion plethysmography. Responses to acetylcholine, but not sodium nitroprusside, were impaired in patients with diabetes (P < 0.001) and in smokers (P < 0.005) compared with control subjects. Administration of uric acid and vitamin C selectively improved acetylcholine responses in patients with type 1 diabetes (P < 0.01) and in regular smokers (P < 0.05). Uric acid administration improved endothelial function in the forearm vascular bed of patients with type 1 diabetes and smokers, suggesting that high uric acid concentrations in vivo might serve a protective role in these and other conditions associated with increased cardiovascular risk.

Acetylcholine↗
PubMed2004

Non-invasive measures of pulse wave velocity correlate with coronary arterial plaque load in humans.

OBJECTIVE: Arterial stiffness is an emerging major risk factor for cardiovascular morbidity and mortality. The aim of the present study was to assess if coronary artery plaque load correlates with non-invasive measures of arterial stiffness. DESIGN: Prospective investigational study. SETTING: Tertiary university hospital centre. PATIENTS: Patients undergoing elective diagnostic coronary angiography. INTERVENTIONS AND MAIN OUTCOME MEASURES: Coronary artery plaque burden was assessed using a 30 MHz intravascular ultrasound catheter during an automated pullback. Proximal coronary artery plaque volume was determined using a validated edge-detection algorithm following three-dimensional computerized reconstruction. Central arterial stiffness was assessed in each patient using applanation tonometry to radial, carotid and femoral pulses, with derivation of aortic pressure augmentation and pulse wave velocity using pulse wave analysis. RESULTS: In 35 patients (61 +/- 2 years), proximal coronary arterial plaque volume was 5.9 +/- 0.6 mm3/mm of vessel. Plaque volume correlated positively with carotid-radial pulse wave velocity (r = 0.47, P = 0.008) and appeared to correlate with carotid-femoral pulse wave velocity (r = 0.34, P = 0.07). Aortic augmentation (r = 0.24, P = 0.16), augmentation index (r = 0.3, P = 0.08), and pulse pressure (r = 0.22, P = 0.2) did not correlate significantly with proximal coronary artery plaque volume. CONCLUSIONS: Non-invasive measures of carotid-radial pulse wave velocity correlate with the extent of coronary artery plaque volume and may be a useful non-invasive surrogate marker for the extent of coronary atherosclerosis. Our findings are consistent with the suggestion that central aortic stiffness may promote the development of coronary atherosclerosis and ischaemic heart disease.

Aged↗
PubMed2003

Comparison of spectrophotometric and enhanced chemiluminescent assays of serum antioxidant capacity.

BACKGROUND: Over recent years, interest in total antioxidant capacity measurement in biological fluids has increased. A number of assays are now available, and we wished to compare an enhanced chemiluminescence (ECL) method to a spectrophotometric method, the total antioxidant status (TAS) assay. METHODS: Serum urate concentration, ECL and TAS were measured in 34 healthy subjects. Additionally, 10 subjects participated in a two-way, randomised crossover study, and received urate 1000 mg or vitamin C 1000 mg intravenously over 1 h. Serum ECL and TAS were measured at 0, 15, 30, 45, 60, 90 and 120 min after commencing infusion. RESULTS: Baseline measurements were poorly correlated between ECL and TAS assays, and between serum urate concentration and each antioxidant assay. There was good correlation between the change in antioxidant capacity detected by both assays during urate infusion (R=0.79, p<0.001, n=60), but not vitamin C infusion. CONCLUSIONS: ECL and TAS measures of serum antioxidant capacity correlate poorly in a healthy population, although both are sensitive to increases in circulating urate concentrations. Therefore, ECL and TAS appear sensitive to different factors. The comparative strengths and weaknesses of various antioxidant assays should be reviewed.

Adult↗
PubMed2003

Acute caffeine intake influences central more than peripheral blood pressure in young adults.

BACKGROUND: The aim of this study was to characterize the acute effects of caffeine on peripheral and central blood pressure (BP) in healthy individuals, using validated noninvasive techniques. METHODS: In a randomized double-blind study, 300 mg caffeine or matching placebo was administered orally to 20 healthy adults and hemodynamic responses were observed. Central BP and augmentation index (AIx) were determined by pulse wave analysis; cardiac index (CI) was estimated by transthoracic bioimpedance; and heart rate variability (HRV) given by power spectral analysis of pulse interval. Pressure amplification (peripheral to central pulse pressure ratio) and systemic vascular resistance index were also calculated. RESULTS: Caffeine administration increased central systolic and diastolic BP by 7 +/- 3 (P <.01) and 3 +/- 2 mm Hg (P <.05), respectively (mean +/- SEM) at 45 min, but had no effect on peripheral BP. Caffeine caused AIx to increase by 7 +/- 2 and 0 +/- 1%, respectively (P <.05), and pressure amplification to decrease by 1.0 +/- 0.1 v 0.2 +/- 0.2 (P <.001) placebo at 45 min. CONCLUSIONS: Acute caffeine intake significantly increases central BP and large artery waveform transmission and diminishes pressure amplification in healthy adults. Therefore, the effects of caffeine on BP may be significantly underestimated by measurement of BP at the brachial artery.

Adolescent↗
PubMed2003

Cardiovascular effects of acute oxygen administration in healthy adults.

Supplementary oxygen is commonly administered in current medical practice. However, attention has recently been drawn to the potentially disadvantageous hemodynamic consequences in certain patients. Possible mechanisms underlying the cardiovascular responses to acute hyperoxia are unclear. The effects of acute oxygen administration on heart rate, blood pressure, cardiac output, systemic vascular resistance, and baroreflex sensitivity were studied in a series of randomised, placebo-controlled studies in healthy individuals, using validated, non-invasive techniques. The effects of oxygen administration on forearm blood flow responses to locally administered acetylcholine, an endothelium-dependent vasodilator, sodium nitroprusside, an endothelium-independent vasodilator, and l-NG-monomethylarginine, a nitric oxide synthase inhibitor, were studied using venous occlusion plethysmography. Oxygen administration for 1 hour caused a reduction in heart rate (P < 0.01) and cardiac index (P < 0.05), and an increase in mean arterial pressure (P < 0.01), systemic vascular resistance (P < 0.05), large artery stiffness (P < 0.05), and baroreflex sensitivity (P < 0.05). There were no effects on vascular responses in the isolated forearm bed. These findings indicate that oxygen administration causes acute effects on cardiovascular function, which might be important in the context of acute illness.

Acetylcholine↗
PubMed2002

Lithium carbonate as a potential pharmacological vehicle: intravenous kinetics of single-dose administration in healthy subjects.

OBJECTIVE: We have been developing lithium carbonate solution as a vehicle for delivery of uric acid in a research setting. We wished to determine the pharmacokinetics of a single systemic administration of 500 mg lithium carbonate (13.5 mmol free Li(+)) in healthy subjects. METHODS: Ten healthy subjects received 500 ml of a 0.1% lithium carbonate and 4% dextrose solution intravenously over 1 h. Serum lithium concentrations were determined at baseline, 15, 30, 45, 60, 75, and 90 min, and 2, 3, 7, 24, and 48 h after the start of infusion for kinetic analysis. RESULTS: Administration led to a time-dependent increase in plasma concentration, followed by a rapid decay of serum lithium concentration. Kinetic analysis showed that the pattern best fit a two-compartment model, with rapid extravascular distribution, an elimination phase half-life of 7.8+/-1.7 h, and clearance of 5.3+/-1.1 l/h. CONCLUSIONS: In healthy subjects, lithium half-life is shorter and clearance is higher than suggested by previous reports in other groups. Administration of 500 ml 0.1% lithium carbonate and 4% dextrose over 1 h is safe, well tolerated, and possibly a suitable vehicle for other agents such as uric acid.

Adolescent↗