25 results on '"Webb, D. J."'
Search Results
2. Local nitric oxide release does not affect tachyphylaxis to angiotensin II in dorsal hand veins in man in the presence of prostaglandin synthesis inhibition
- Author
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de Haas, S. L, Wilkinson, I. B, Boyd, J. L, and Webb, D. J
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- 2002
3. Clinical pharmacology and therapeutics in a changing world
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Bateman, D. N., McInnes, G. T., and Webb, D. J.
- Published
- 1999
4. The peptide endothelin receptor antagonist, TAK-044, produces sustained inhibition of endothelin-1 mediated arteriolar vasoconstriction
- Author
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Ferro, C. J., Haynes, W. G., Johnston, N. R., Lomax, C. C., Newby, D. E., and Webb, D. J.
- Published
- 1997
5. Developing a core curriculum in clinical pharmacology and therapeutics: a Delphi study
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Walley, T. and Webb, D. J.
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- 1997
6. Core content of a course in Clinical Pharmacology
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Walley, T. and Webb, D. J.
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- 1997
7. Endothelin: from molecule to man
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Webb, D. J.
- Published
- 1997
8. Long-term adverse effects of paracetamol - a review
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McCrae, J. C., primary, Morrison, E. E., additional, MacIntyre, I. M., additional, Dear, J. W., additional, and Webb, D. J., additional
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- 2018
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9. ACE inhibitors
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Kelland, N. F., primary and Webb, D. J., additional
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- 2002
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10. Venous occlusion plethysmography in cardiovascular research: methodology and clinical applications.
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Wilkinson IB and Webb DJ
- Subjects
- Capillary Permeability physiology, Endothelium, Vascular physiology, Forearm blood supply, Humans, Nitric Oxide metabolism, Plethysmography instrumentation, Regional Blood Flow physiology, Reproducibility of Results, Research, Vascular Resistance physiology, Cardiovascular Physiological Phenomena, Plethysmography methods
- Published
- 2001
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11. Adrenomedullin (ADM) in the human forearm vascular bed: effect of neutral endopeptidase inhibition and comparison with proadrenomedullin NH2-terminal 20 peptide (PAMP).
- Author
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Wilkinson IB, McEniery CM, Bongaerts KH, MacCallum H, Webb DJ, and Cockcroft JR
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- Adrenomedullin, Adult, Blood Flow Velocity drug effects, Brachial Artery drug effects, Brachial Artery physiology, Double-Blind Method, Forearm physiology, Heart Rate drug effects, Humans, Infusions, Intra-Arterial, Male, Middle Aged, Neprilysin antagonists & inhibitors, Norepinephrine pharmacology, Plethysmography, Protease Inhibitors pharmacology, Thiorphan pharmacology, Vasoconstrictor Agents pharmacology, Peptide Fragments pharmacology, Peptides pharmacology, Proteins pharmacology, Vasodilation drug effects, Vasodilator Agents pharmacology
- Abstract
Aims: To compare the haemodynamic responses of proadrenomedullin N-terminal 20 peptide (PAMP) and adrenomedullin (ADM) in the forearm vascular bed of healthy male volunteers, and to investigate the role of neutral endopeptidase (NEP) in the metabolism of ADM., Methods: On two separate occasions, ADM (1-30 pmol x min(-1)) and PAMP (100-3000 pmol x min(-1)) were infused into the brachial artery of eight male subjects, and forearm blood flow (FBF) assessed using venous occlusion plethysmography. In a second study, eight male subjects received the same doses of ADM, co-infused with either the NEP inhibitor thiorphan (30 nmol x min(-1)) or the control vasoconstrictor noradrenaline (120 pmol x min(-1)), on separate occasions. Both studies were conducted in a double-blind, randomized manner., Results: ADM and PAMP produced a dose-dependent increase in FBF (P < or = 0.002). Based on the dose producing a 50% increase in FBF, ADM was approximately 60 times more potent than PAMP. Thiorphan and noradrenaline produced similar reductions in FBF of 14 +/- 4% (mean +/- s.e. mean) and 22 +/- 6%, respectively (P = 0.4). However, the area under the dose-response curve was significantly greater during co-infusion of ADM with thiorphan than with noradrenaline (P = 0.028), as was the maximum increase in FBF ratio (2.1 +/- 1.0 vs 1.2 +/- 0.2; P = 0.030)., Conclusions: ADM and PAMP both produce a local dose-related vasodilatation in the human forearm, but PAMP is approximately 60 times less potent than ADM. In addition, NEP inhibition potentiates the haemodynamic effects of ADM. These findings suggest that PAMP may not play a role in the physiological regulation of blood flow. However, in pathophysiological conditions such as hypertension and heart failure, NEP inhibition may exert a beneficial effect by increasing the biological activity of ADM.
- Published
- 2001
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12. Constriction to ETB receptor agonists, BQ-3020 and sarafotoxin s6c, in human resistance and capacitance vessels in vivo.
- Author
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Strachan FE, Crockett TR, Mills NL, Gray GA, and Webb DJ
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- Adolescent, Adult, Blood Flow Velocity drug effects, Heart Rate drug effects, Humans, Infusions, Intra-Arterial, Infusions, Intravenous, Male, Receptor, Endothelin B, Endothelins administration & dosage, Forearm blood supply, Peptide Fragments administration & dosage, Receptors, Endothelin agonists, Vascular Capacitance drug effects, Vascular Resistance drug effects, Vasoconstriction drug effects, Vasoconstrictor Agents administration & dosage, Viper Venoms administration & dosage
- Abstract
Aims: The aim of the study was to examine the effects of the ETB receptor selective agonists sarafotoxin S6c (SFTX6c) and BQ-3020 on the forearm resistance and capacitance vessels in healthy subjects in vivo., Methods: The local response to intra-arterial or intravenous infusion of SFTX6c (5 pmol min-1) or BQ-3020 (50 pmol min-1) was assessed, on separate occasions, in eight healthy men (aged 20-28 years). Data (mean +/- s.e.mean) were examined by ANOVA. Results are expressed as percentage change from baseline at 90 min., Results: SFTX6c and BQ-3020 reduced forearm blood flow, following local intra-arterial infusion (-25 +/- 7% and -27 +/- 7%, respectively; P < 0.001) and reduced hand vein diameter, following local intravenous infusion (-30 +/- 8% and -16 +/- 7%, respectively; P < 0.001)., Conclusions: We have shown that locally active infusions of the selective ETB receptor agonists SFTX6c and BQ-3020 cause arterial constriction and venoconstriction in healthy human blood vessels in vivo. These results indicate that ETB receptor stimulation may mediate vasoconstriction in humans.
- Published
- 2000
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13. Substance P-induced vasodilatation is mediated by the neurokinin type 1 receptor but does not contribute to basal vascular tone in man.
- Author
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Newby DE, Sciberras DG, Ferro CJ, Gertz BJ, Sommerville D, Majumdar A, Lowry RC, and Webb DJ
- Subjects
- Acetals adverse effects, Antiemetics adverse effects, Antiemetics pharmacology, Aprepitant, Blood Pressure drug effects, Cross-Over Studies, Dose-Response Relationship, Drug, Double-Blind Method, Drug Interactions, Forearm physiology, Humans, Male, Morpholines adverse effects, Regional Blood Flow drug effects, Substance P adverse effects, Acetals pharmacology, Morpholines pharmacology, Neurokinin-1 Receptor Antagonists, Receptors, Neurokinin-1 metabolism, Substance P pharmacology, Vasodilation drug effects
- Abstract
Aims: Following intravenous administration of its prodrug, L-758,298, we assessed the pharmacodynamics of L-754,030, a novel and highly selective NK1 receptor antagonist, by examining systemic haemodynamics and the blood flow responses to intra-arterial substance P infusion., Methods: Sixteen healthy male volunteers participated in a double-blind, randomised, placebo controlled crossover trial of L-758 298. Forearm blood flow was measured using venous occlusion plethysmography during intrabrachial substance P infusion (0.125-128 pmol min-1 ). In part 1, eight subjects received substance P infusions before and during placebo, 0.25 mg, 1 mg or 5 mg of L-758 298. In part 2, eight subjects received substance P infusions 24 h after placebo or 1.43 mg of L-758 298., Results: L-758 298 caused dose dependent inhibition of substance P induced vasodilatation (P<0.001). Placebo adjusted differences (95% CI) in baseline forearm blood flow, mean arterial pressure and heart rate showed no relevant changes with 5 mg of L-758 298 (>1400-fold shift in substance P response): 0.00 (-0.49 to +0.49) ml 100 ml-1 min-1, 1. 0 (-3.2 to +5.2) mmHg and 1.9 (-5.9 to +9.7) beats min-1, respectively. Twenty-four hours after 1.43 mg of L-758,298, there was approximately 34-fold shift in response to substance P induced vasodilatation (P<0.008) at plasma L-754 030 concentrations of 2-3 ng ml-1. L-758 298 was generally well tolerated without serious adverse events., Conclusions: Substance P induced forearm vasodilatation is mediated by the endothelial cell NK1 receptor in man but endogenous substance P does not appear to contribute to the maintenance of peripheral vascular tone or systemic blood pressure.
- Published
- 1999
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14. Impaired cholinergic dilator response of resistance arteries isolated from patients with Raynaud's disease.
- Author
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Smith PJ, Ferro CJ, McQueen DS, and Webb DJ
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- Acetylcholine pharmacology, Adult, Arteries physiopathology, Cold Temperature, Dose-Response Relationship, Drug, Endothelium, Vascular physiology, Female, Humans, In Vitro Techniques, Male, Middle Aged, Nitroprusside pharmacology, Vascular Resistance drug effects, Vasodilation drug effects, Arteries drug effects, Raynaud Disease physiopathology, Vasodilator Agents pharmacology
- Abstract
Aims: We examined the effect of cooling on the response to the endothelium-dependent and -independent dilators, acetylcholine (ACh) and sodium nitroprusside (SNP), respectively, in human microvessels in vitro, and compared the responses between Raynaud's disease (RD) patients and controls, in order to assess the pathogenic role of the endothelium in RD., Methods: Subcutaneous resistance arteries were dissected from gluteal fat biopsies taken from patients with RD (n=18) and from age-and sex-matched control subjects (n=17). Vessels were cannulated in a small vessel arteriograph, in which a pressure of 50 mmHg was maintained across the vessel wall. Cumulative concentration-response curves for ACh (10-10-10-4 m ) and SNP (10-10-10-3 m ) were generated in vessels at either 37 degrees C or 24 degrees C, with endothelium intact for ACh and removed for SNP (n=6 per group)., Results: Neither dilator showed significant differences in sensitivity when comparing responses between vessels from RD patients and controls, at either temperature, but the maximal relaxation to ACh was depressed in vessels from RD patients compared with controls at 37 degrees C (Emax=45+/-13 in RD vs 89+/-4 in controls; P=0.004)., Conclusions: These results support the hypothesis that impaired endothelium-dependent vasodilatation is involved in the pathophysiology of RD.
- Published
- 1999
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15. Studies with iontophoretic administration of drugs to human dermal vessels in vivo: cholinergic vasodilatation is mediated by dilator prostanoids rather than nitric oxide.
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Noon JP, Walker BR, Hand MF, and Webb DJ
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- Acetylcholine pharmacology, Adult, Aspirin pharmacology, Enzyme Inhibitors pharmacology, Humans, Male, Nitroprusside administration & dosage, Nitroprusside pharmacology, Norepinephrine pharmacology, Skin drug effects, Vasoconstrictor Agents pharmacology, omega-N-Methylarginine pharmacology, Acetylcholine administration & dosage, Iontophoresis, Nitric Oxide physiology, Prostaglandins physiology, Skin blood supply, Vasodilation drug effects
- Abstract
Aims: Impaired function of the vascular endothelium has been well documented in hypertension and hypercholesterolaemia. However, the 'gold standard' method for assessing endothelial function, using intra-arterial drug infusion, is invasive and has only been applied in the forearm and coronary circulations in vivo. The aim of the present study was to establish the non-invasive technique of transdermal drug iontophoresis to assess endothelial function in human dermal vessels in vivo., Methods: In healthy male volunteers, we delivered acetylcholine (ACh) and sodium nitroprusside (SNP) to dermal vessels of the forearm using iontophoresis, and measured vasodilatation using laser Doppler fluximetry. Drugs were diluted in a methylcellulose gel vehicle which did not induce vasodilatation. To assess the contribution of nitric oxide and vasoactive prostanoids to cholinergic dilatation, the procedure was repeated during brachial artery infusion of the nitric oxide synthase inhibitor, L-N(G)-monomethyl-arginine (L-NMMA) and after intravenous administration of the cyclooxygenase inhibitor, aspirin. As a control for the vasoconstrictor effect of L-NMMA, which was measured by venous occlusion plethysmography, iontophoresis was repeated during brachial artery infusion of noradrenaline., Results: Flux increased in response to iontophoresis of ACh (from 45 +/- 9 to 499 +/- 80 units; P < 0.0001) and SNP (from 32 +/- 11 to 607 +/- 82 units; P < 0.0001). Brachial artery infusions of L-NMMA or noradrenaline caused reductions in forearm blood flow (by 43 +/- 2% and 44 +/- 2%, respectively) but did not inhibit vasodilatation in response to iontophoresis of ACh or SNP. In contrast, aspirin inhibited the response to iontophoresis of ACh (from 473 +/- 81 to 222 +/- 43 units; P < 0.0001) but did not affect the response to SNP (from 348 +/- 59 to 355 +/- 58)., Conclusions: We conclude that in healthy subjects, in contrast to the forearm circulation, dermal vasodilatation in response to iontophoresis of ACh is mediated predominately by a dilator prostanoid rather than by nitric oxide generation. Furthermore, the non-invasive technique of iontophoresis could complement existing invasive tests of endothelial function in future clinical studies.
- Published
- 1998
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16. The clinical section of the British Pharmacological Society: prospects for the future.
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Baber NS, Tucker GT, and Webb DJ
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- Humans, Societies, Medical trends, United Kingdom, Pharmacology, Clinical trends, Societies, Pharmaceutical trends
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- 1997
- Full Text
- View/download PDF
17. Intra-arterial substance P mediated vasodilatation in the human forearm: pharmacology, reproducibility and tolerability.
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Newby DE, Sciberras DG, Mendel CM, Gertz BJ, Boon NA, and Webb DJ
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- Adult, Blood Pressure drug effects, Brachial Artery, Dose-Response Relationship, Drug, Heart Rate drug effects, Humans, Infusions, Intra-Arterial, Male, Plethysmography, Regional Blood Flow drug effects, Reproducibility of Results, Substance P administration & dosage, Vasodilator Agents administration & dosage, Forearm blood supply, Substance P pharmacology, Vasodilation drug effects, Vasodilator Agents pharmacology
- Abstract
Aims: The current studies were designed to characterize the pharmacology, reproducibility and tolerability of the vasodilator response to intra-arterial substance P infusion in the forearm of healthy man., Methods: On different occasions, eight healthy male volunteers received brachial artery infusions of substance P at doubling doses ranging from 0.5 to 128 pmol min(-1). Blood flow was measured in both arms using venous occlusion plethysmography., Results: Substance P induced dose-dependent vasodilatation in the human forearm which had a log-linear relationship to dose. At doses of 1-8 pmol min(-1), mean responses were highly reproducible both within and between days. There were no differences between responses to discontinuous doses and continuous doses of substance P. Substance P was generally well tolerated at doses of < or = 64 pmol min(-1) with no significant alteration in arterial blood pressure or heart rate. Skin oedema in the infused forearm and systemic vasodilatation, manifested by facial flushing and non-infused forearm vasodilatation, occurred at doses of > or = 16 pmol min(-1)., Conclusions: Forearm vasodilatation to substance P represents a reproducible and useful model in the assessment of peripheral endothelial cell NK1 receptor function.
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- 1997
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18. An investigation into the direct and indirect venoconstrictor effects of endothelin-1 and big endothelin-1 in man.
- Author
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Haynes WG, Moffat S, and Webb DJ
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- Adult, Aspartic Acid Endopeptidases blood, Endothelin-1, Endothelin-Converting Enzymes, Endothelins administration & dosage, Humans, Infusions, Intravenous, Male, Metalloendopeptidases, Protein Precursors administration & dosage, Vasoconstrictor Agents administration & dosage, Veins enzymology, Veins physiology, Endothelins pharmacology, Protein Precursors pharmacology, Vasoconstrictor Agents pharmacology, Veins drug effects
- Abstract
1. Endothelin-1 is a potent endothelium-derived vasoconstrictor peptide that is generated through cleavage of its precursor big endothelin-1 by 'endothelin converting enzyme' (ECE) in resistance vessels, including those of the forearm vascular bed. In some animal tissues, but not in resistance vessels of healthy human subjects, endothelin-1 appears to potentiate the actions of the sympathetic nervous system. We examined whether ECE activity is present in human hand veins and whether endothelin-1 or big endothelin-1 potentiate sympathetically mediated venoconstriction. 2. Six healthy subjects received dorsal hand vein infusion of local, non-systemic doses of endothelin-1 (5 pmol min-1), big endothelin-1 (50 pmol min-1) and, as a control, sodium chloride (0.9%; w/v) for 90 min. Vein diameter was measured using the Aellig displacement technique. Sympathetically mediated venoconstriction was elicited using the single deep breath reflex. 3. Endothelin-1 caused a progressive decrease in hand vein diameter, by 49% at 90 min (95% confidence intervals [CI]: -68 to -30%; P = 0.0001). Vein diameter did not change significantly after 90 min infusion of big endothelin-1 (+3%; CI: -11 to +17%; P = 0.0007 vs endothelin-1; P = 0.40 vs baseline) or sodium chloride (+2%; CI: -12 to +16%; P = 0.0002 vs endothelin-1; P = 0.60 vs baseline). Venoconstriction to deep breath was not potentiated by endothelin-1. 4. These results suggest that, in contrast to the situation in forearm resistance vessels, there is little or no local ECE activity in human hand veins and that endothelin does not potentiate sympathetic responses in these cutaneous capacitance vessels.
- Published
- 1995
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19. Local L-NG-monomethyl-arginine attenuates the vasodilator action of bradykinin in the human forearm.
- Author
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O'Kane KP, Webb DJ, Collier JG, and Vallance PJ
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- Adult, Arginine administration & dosage, Arginine pharmacology, Bradykinin administration & dosage, Dose-Response Relationship, Drug, Forearm blood supply, Humans, Male, Middle Aged, Nitroglycerin pharmacology, Norepinephrine administration & dosage, Norepinephrine pharmacology, Regional Blood Flow drug effects, omega-N-Methylarginine, Arginine analogs & derivatives, Bradykinin pharmacology, Nitric Oxide antagonists & inhibitors, Vasodilation drug effects
- Abstract
1. Studies in animals indicate that bradykinin relaxes blood vessels directly through an action on smooth muscle and indirectly through the release of endothelium-derived mediators. Its precise mechanism of action in the human arterial circulation is not yet known. 2. In this study the effects of a specific inhibitor of nitric oxide synthase, L-NG-monomethyl-arginine (L-NMMA) and noradrenaline on the vasodilator responses to bradykinin were examined in the forearm arterial bed of healthy volunteers. Noradrenaline was used as a control for vasoconstriction by L-NMMA; glyceryl trinitrate (GTN) as a control vasodilator acting independently of the NO synthase enzyme. 3. L-NMMA (4 mumol min-1; 5 min) alone reduced resting forearm blood flow by 44% (P < 0.01; n = 6) confirming that nitric oxide plays an important role in regulating vascular tone. 4. Bradykinin (10 and 100 pmol min-1; 3 min each dose) and GTN (2 and 5 nmol min-1; 3 min each dose) increased forearm blood flow in a dose-dependent manner (percentage changes 171 +/- 17% and 398 +/- 35%, and 176 +/- 21% and 268 +/- 42%, respectively; n = 6). 5. The response to bradykinin, but not that to GTN, was attenuated by L-NMMA compared with noradrenaline (P < 0.05; n = 6), suggesting that bradykinin-induced vasodilatation in the forearm is mediated, at least in part, by stimulating release of nitric oxide.
- Published
- 1994
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20. Screening for human immunodeficiency virus: a survey of British clinical pharmacology units.
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Thomson M, Haynes WG, and Webb DJ
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- Adolescent, Adult, Aged, Clinical Trials, Phase I as Topic, Clinical Trials, Phase II as Topic, Health Facility Size, Humans, Mass Screening ethics, Middle Aged, Pharmacology, Clinical ethics, Physical Examination, Professional Practice standards, Surveys and Questionnaires, United Kingdom, HIV Infections diagnosis, Health Facilities standards, Mass Screening methods, Pharmacology, Clinical standards
- Abstract
1. A survey of screening practices used to detect infection with the human immunodeficiency virus (HIV), covering the 12 months from June 1990 to May 1991, was carried out in 74 clinical pharmacology units performing phase I and II studies. Forty-five units were identified from the Technomark commercial register, and 29 units were identified from the clinical academic membership of the British Pharmacological Society. 2. An overall response rate of 92% was obtained: 41 replies from commercial units; 27 replies from academic units. Seventeen commercial units and 26 academic units reported involvement with healthy volunteer studies; these were the 43 questionnaires analysed. 3. The majority of clinical pharmacology units did not believe that it was necessary to perform HIV screening by HIV antibody testing. Six commercial units (35%) and three academic units (12%) did perform HIV antibody testing in healthy volunteers. 4. Reasons frequently given for testing were protection of clinical and laboratory staff, and the advantages to the volunteer of prophylaxis and treatment at an early stage of HIV infection. Reasons for not testing included the perceived low risk of a positive test, a lack of benefit from treatment, and the adverse implications in relation to health insurance. Advice from an Ethics Review Committee was not generally a reason for testing. 5. In future, screening patterns may change, depending on prevalence of HIV positivity in the community, the benefits of diagnosis and treatment, and the perceived or real disadvantages of having an HIV antibody test. For the present, we believe that indirect methods, such as an HIV risks questionnaire, are more appropriate than direct antibody testing.
- Published
- 1993
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21. Ethics of volunteer research: the role of new EC guidelines.
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Haynes WG and Webb DJ
- Subjects
- Compensation and Redress, Drug Industry, Ethics Committees, Research, Europe, Government Regulation, Humans, Informed Consent, Internationality, Research Subjects, Risk Assessment, Volunteers, Ethics, Medical, Human Experimentation, Nontherapeutic Human Experimentation, Research Design, Social Control, Formal
- Published
- 1991
22. The effect of intra-arterial endothelin on resting blood flow and sympathetically mediated vasoconstriction in the forearm of man.
- Author
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Cockcroft JR, Clarke JG, and Webb DJ
- Subjects
- Adult, Dose-Response Relationship, Drug, Endothelins administration & dosage, Humans, Injections, Intra-Arterial, Lower Body Negative Pressure, Male, Norepinephrine administration & dosage, Norepinephrine pharmacology, Endothelins pharmacology, Forearm blood supply, Regional Blood Flow drug effects, Sympathetic Nervous System drug effects, Vasoconstriction drug effects
- Abstract
1. The hypothesis that endothelin (ET) influences sympathetically mediated vasoconstriction was investigated in 13 healthy, male subjects. 2. ET (1 pmol min-1) was infused for 60 min into the left brachial arteries of seven healthy male subjects. Resting forearm blood flow, and sympathetic vasoconstriction produced by lower body negative pressure (LBNP; 15 mm Hg), was measured in both arms by strain gauge plethysmography. In a further six subjects, noradrenaline (NA) was infused intra-arterially at doses of 150-600 pmol min-1, with and without co-infusion of ET (1 pmol min-1), with blood flow measured in both forearms. 3. ET produced a small but significant reduction of blood flow in the infused forearm from 3.9 +/- 0.6 ml 100 ml-1 min-1 during infusion of saline, to 3.3 +/- 0.7 ml 100 ml-1 min-1 during infusion of ET at 60 min (P less than 0.05). Blood flow in the non-infused forearm was not altered by ET infusion. 4. NA produced a significant and dose-dependent reduction of blood flow in the infused forearm from 3.13 +/- 0.5 ml 100 ml-1 min-1 during saline infusion, to 1.49 +/- 0.2 ml 100 ml-1 min-1 with NA at 600 pmol min-1 (P less than 0.001). During co-infusion of ET, blood flow was reduced similarly in the infused arm from 3.15 +/- 0.7 ml 100 ml-1 min-1 during saline infusion to 1.55 +/- 0.2 ml 100 ml-1 min-1 with NA at 600 pmol min-1. Blood flow in the non-infused arm was not altered by ET and NA infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1991
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23. The effect of local converting enzyme inhibition on the dilator response to substance P in the human forearm.
- Author
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Benjamin N and Webb DJ
- Subjects
- Adult, Dose-Response Relationship, Drug, Enalapril pharmacology, Humans, Male, Regional Blood Flow drug effects, Substance P metabolism, Angiotensin-Converting Enzyme Inhibitors pharmacology, Forearm blood supply, Substance P pharmacology, Vasodilation drug effects
- Abstract
It has been proposed that angiotensin converting enzyme (ACE) may play a part in the metabolism of substance P. Reduced metabolism following treatment with ACE inhibitors may cause accumulation of substance P to produce the adverse effect of cough. It has been shown in this study that, in contrast to angiotensin I and bradykinin, inhibition of local vascular ACE does not interfere with the vascular effects of substance P on forearm resistance vessels when this peptide is infused into the brachial artery of normal volunteers. These results suggest that endothelial ACE plays little part in the metabolism of intravascular substance P.
- Published
- 1990
- Full Text
- View/download PDF
24. Vascular responses to local atrial natriuretic peptide infusion in man.
- Author
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Webb DJ, Benjamin N, Allen MJ, Brown J, O'Flynn M, and Cockcroft JR
- Subjects
- Adult, Atrial Natriuretic Factor blood, Dose-Response Relationship, Drug, Humans, Infusions, Intra-Arterial, Muscles blood supply, Regional Blood Flow drug effects, Skin blood supply, Vasodilation drug effects, Atrial Natriuretic Factor pharmacology, Blood Vessels drug effects
- Abstract
1. The effect on skin and muscle blood flow of arterial infusion of atrial natriuretic peptide (ANP) directly into the forearm circulation, and on venous tone of direct infusion into a dorsal hand vein, was studied in normal subjects. 2. ANP produced a dose-dependent increase in both skin and muscle blood flow, but at equivalent doses, produced no dilatation of noradrenaline-preconstricted dorsal hand veins. These findings indicate that ANP acting locally, is an arterioselective dilator in the upper limb circulation in normal man. 3. Measurements of ANP in venous plasma during arterial infusion suggest marked clearance of ANP across the forearm vascular bed. Such peripheral clearance may, at least in part, account for the short plasma half-life of this peptide. 4. The lowest dose of ANP infused was calculated to produce plasma levels similar to those found in patients with heart failure. The findings with this dose suggest that, in heart failure, circulating levels of ANP may be within a range capable of influencing peripheral vascular resistance directly.
- Published
- 1988
- Full Text
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25. The potassium channel opening drug cromakalim produces arterioselective vasodilation in the upper limbs of healthy volunteers.
- Author
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Webb DJ, Benjamin N, and Vallance P
- Subjects
- Adult, Arteries physiology, Cromakalim, Forearm blood supply, Hand blood supply, Humans, Infusions, Intra-Arterial, Infusions, Intravenous, Male, Norepinephrine pharmacology, Regional Blood Flow drug effects, Vascular Resistance drug effects, Arteries drug effects, Benzopyrans pharmacology, Parasympatholytics pharmacology, Potassium Channels drug effects, Pyrroles pharmacology, Vasodilation drug effects
- Abstract
1. The effect of the K+ channel opening drug cromakalim on forearm blood flow during direct infusion into the brachial artery, and on the size of noradrenaline preconstricted hand veins during infusion directly into the vein, was studied in eight healthy volunteers. 2. Cromakalim (0.01-10.0 micrograms min-1) produced a dose-dependent increase in blood flow in the infused forearm, from 5.4 +/- 2.5 to 15.1 +/- 7.3 ml 100 ml-1 forearm min-1 at 10 micrograms min-1 (P less than 0.001). The half-time of offset of its action was 30 min. There was no change in blood flow in the non-infused forearm. 3. There was no increase in the size of noradrenaline pre-constricted dorsal veins during local infusion of cromakalim (0.001-1.0 microgram min-1). Glyceryl trinitrate (0.4 microgram min-1) however, completely reversed the constriction to noradrenaline (P less than 0.001). 4. The clear arterioselectivity of cromakalim, as with other members of this new class of drug, accords with the dependency of venoconstriction on receptor-operated, rather than potential-operated mechanisms which are of importance in resistance vessels. With this haemodynamic profile cromakalim may prove of value in the treatment of arterial hypertension.
- Published
- 1989
- Full Text
- View/download PDF
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