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N A Boon

Publications and source records attributed to N A Boon.

At least 19 recordsLinked to original sources

Comparison of forearm vasodilatation to substance P and acetylcholine: contribution of nitric oxide.

1. Forearm blood flow responses to incremental challenges of acetylcholine and substance P, administered via the brachial artery, were measured by venous occlusion plethysmography in eight subjects in the presence of saline, the nitric oxide synthase inhibitor, NG-monomethyl-L-arginine, and a control vasoconstrictor, noradrenaline. 2. Substance P and acetylcholine caused dosedependent increases in forearm blood flow (P < 0.001). When separated by 30 min saline infusions, repeated responses did not undergo tachyphylaxis. 3. Noradrenaline caused a mean reduction in basal blood flow of 34-51% (P < 0.001), and augmented the percentage increases in blood flow with both substance P (P = 0.05) and acetylcholine (P = 0.03) infusions. 4. NG-Monomethyl-L-arginine caused a mean reduction in basal blood flow of 42-45% (P < 0.001) and significantly inhibited the responses to both substance P (P < 0.001) and acetylcholine (P = 0.05). 5. In comparison with saline responses, NG-monomethyl-L-arginine caused a mean inhibition of 69 +/- 8% for substance P-induced vasodilatation and 40 +/- 5% for acetylcholine-induced vasodilatation. However, comparing responses with those to the control vasoconstrictor noradrenaline, NG-monomethyl-L-arginine caused a mean inhibition of 81 +/- 5% for substance P responses and 58 +/- 3% for acetylcholine responses. Inhibition by NG-monomethyl-L-arginine of the response to substance P was significantly greater than inhibition of the response to acetylcholine (P = 0.02). 6. Hence, in healthy men, a greater proportion of the forearm vasodilatation to substance P than to acetylcholine appears to be nitric oxide-mediated. Given its greater stability, substance P may be more suitable as a pharmacological tool in the investigation of stimulated nitric oxide production and endothelial cell function.

Acetylcholine

Intra-arterial substance P mediated vasodilatation in the human forearm: pharmacology, reproducibility and tolerability.

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.

Adult

Caffeine restriction has no role in the management of patients with symptomatic idiopathic ventricular premature beats.

OBJECTIVE: To assess the role of caffeine restriction in the management of patients with symptomatic idiopathic ventricular premature beats. DESIGN: A randomised, double blind, 6 week intervention trial incorporating dietary caffeine restriction, caffeinated coffee, and decaffeinated coffee. SETTING: Cardiac outpatient clinic. PATIENTS: 13 patients with symptomatic frequent idiopathic ventricular premature beats. MAIN OUTCOME MEASURES: Weekly measures of serum caffeine concentration, coffee consumption, visual analogue score of palpitations, and 24 hour ventricular premature beat frequency. RESULTS: The interventions achieved significant alterations in serum caffeine concentrations (P < 0.001) which correlated with coffee consumption (r = 0.70; P < 0.001). Visual analogue palpitation scores showed a small, but significant correlation with ventricular premature beat frequencies (r = 0.34; P = 0.003). However, there were no significant changes in palpitation scores or ventricular premature beat frequencies during the intervention weeks and no significant correlations were found between these variables and serum caffeine concentrations. CONCLUSIONS: Caffeine restriction has no role in the management of patients referred with symptomatic idiopathic ventricular premature beats.

Caffeine

A review of endocarditis in acquired immunodeficiency syndrome and human immunodeficiency virus infection.

Non-bacterial thrombotic endocarditis (NBTE) was frequently identified in early post-mortem studies of patients with HIV infection, but has not been reported since 1989. The reason for this apparent decline is not clear, but it is possible that the prevalence of the condition was overestimated in the past. We have found no evidence of NBTE in our series of 110 autopsies on subjects from all major risk groups and at various stages of immune deficiency [intravenous drug user (IVDU)-AIDS 35% (39/110), IVDU-pre AIDS 36% (40/110), homosexual-AIDS 25% (28/110), blood product recipients-AIDS 1.8% 2/110), African 0.9% (1/110)]. Infective endocarditis (IE) in HIV infection occurs almost exclusively in intravenous drug users and is rare in other HIV-positive patients. However, asymptomatic HIV infection appears to have little effect on the susceptibility to or the mortality from endocarditis and it is, therefore, appropriate to institute antimicrobial treatment in these cases. The majority (54.4%) of the 960 HIV-positive individuals in the Lothian region of Scotland are young adults who contracted the virus through IVDU around 1983. However, a prospective echocardiological study of 269 patients over four years (IVDU 69%, homosexual 18%, heterosexual 8%, bisexual 3%, multiple risk factors 1%) has demonstrated only four cases of infective endocarditis. We believe this reflects the prevalence of current parenteral drug use in our cohort which has fallen with the introduction of an oral drug replacement programme.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Opportunistic Infections

Heart muscle disease related to HIV infection: prognostic implications.

OBJECTIVES: To determine the natural course of heart muscle disease in patients infected with HIV. DESIGN: Prospective echocardiographic survey and observational study over four years. SETTING: Edinburgh. SUBJECTS: 296 adults infected with HIV (mean age 32.7 years (range 21.5 to 67.6) drawn from all the major groups at risk of HIV infection in Britain. MAIN OUTCOME MEASURES: Detection of myocardial dysfunction and time to death from index echocardiogram in serial echocardiography. RESULTS: Cardiac dysfunction was identified in 44 subjects (dilated cardiomyopathy, 13; isolated right ventricular dysfunction, 12; borderline left ventricular dysfunction, 19). Dilated cardiomyopathy was strongly associated with a CD4 cell count of < 100 x 10(6)/l, in contrast with the other forms of cardiac dysfunction. During the study 12/13 (92%) subjects with dilated cardiomyopathy, 5/12 (42%) with right ventricular dysfunction, and 8/19 (42%) with borderline left ventricular function died of conditions related to AIDS. Survival was significantly reduced in the subjects with dilated cardiomyopathy compared with those with normal hearts (P < 0.001). The median survival from the index echocardiogram was 101 days (95% confidence interval 42 to 146) for the subjects with cardiomyopathy compared with 472 days (383 to 560) for those with normal hearts and a CD4 cell count of < 20 x 10(6)/l. No significant difference existed in survival for subjects with borderline left or isolated right ventricular dysfunction. CONCLUSION: Even after adjustment for the significantly reduced CD4 cell count with which dilated cardiomyopathy is associated, the outlook for patients with HIV infection and dilated cardiomyopathy is poor. Isolated right and borderline left ventricular dysfunction are not associated with reduced CD4 cells counts and do not carry adverse prognostic implications.

Acquired Immunodeficiency Syndrome

The long-term effects of metoprolol and epanolol on tissue-type plasminogen activator and plasminogen activator inhibitor 1 in patients with ischaemic heart disease.

This double-blind, randomized parallel group study investigated the effect of 6 months beta-adrenoceptor antagonist therapy with either metoprolol (beta 1-selective without intrinsic sympathomimetic activity [ISA]) or epanolol (beta 1-selective with ISA) on markers of endogenous fibrinolysis in 20 patients with chronic stable angina receiving concurrent treatment with nifedipine. Neither drug had an effect on tissue-type plasminogen activator or plasminogen activator inhibitor type 1 (PAI-1). A significant correlation between fasting insulin and PAI-1 has previously been described and was confirmed in this study. The group treated with metoprolol showed a significant rise in fasting insulin after 6 months with no change in PAI-1. This suggests that the previously described link between these two may not be causal.

Adrenergic beta-Antagonists

Hyperinsulinaemia in ischaemic heart disease: the importance of myocardial infarction and left ventricular function.

Elevated circulating insulin levels have been reported in ischaemic heart disease, and may be of aetiological importance. Previous studies have not considered the potential influence of heart failure or of previous myocardial infarction, as opposed to stable angina. We therefore measured the insulin response to a 75 g oral glucose tolerance test in five groups with normal glucose tolerance, comparing normal male controls to men with chronic stable angina, men with recent myocardial infarction (two groups, 3 weeks and 3 months post infarction), and men with chronic severe heart failure. Only patients with chronic heart failure had fasting hyperinsulinaemia, probably reflecting associated neuroendocrine abnormalities. Stimulated hyperinsulinaemia was present in all patient groups, but was less pronounced and of shorter duration in patients with angina. At 120 min, only patients with heart failure or previous myocardial infarction were hyperinsulinaemic. The degree of stimulated hyperinsulinaemia was not influenced by the presence of heart failure or by the length of time from infarction. Hyperinsulinaemia is associated with impaired peripheral muscle glucose uptake and metabolism, and might contribute to muscular fatigue on exertion in patients with previous myocardial infarction or heart failure.

Administration, Oral

Cardiac dysfunction in paediatric HIV infection.

A child under long term surveillance for vertically acquired HIV-I infection developed respiratory symptoms. Dilated cardiomyopathy was diagnosed. Clinical and echocardiographic assessment of six other children with symptomatic HIV disease showed no evidence of cardiac dysfunction. The exact prevalence of this complication in paediatric HIV infection is unknown, but the potential diagnostic difficulties are highlighted.

Cardiomyopathy, Dilated

Effects of haemodialysis and continuous ambulatory peritoneal dialysis on abnormalities of ion transport in vivo in patients with chronic renal failure.

1. We have studied Na+/K+ pump activity in vivo in three groups of subjects: patients with chronic renal failure not receiving maintenance dialysis, patients being treated by either haemodialysis or continuous ambulatory peritoneal dialysis, and matched control subjects. 2. To do this we have measured the changes in plasma and intraerythrocytic rubidium concentrations after an oral load of rubidium chloride, having previously shown that changes in the disposition of rubidium measured in this way reflect changes in the activity of the Na+/K+ pump in vivo. 3. Erythrocyte rubidium uptake was significantly reduced both in ten patients with chronic renal failure not receiving maintenance dialysis and in 12 patients being treated by haemodialysis, when compared with 31 healthy control subjects. In contrast, erythrocyte rubidium uptake was not altered in 13 patients treated by continuous ambulatory peritoneal dialysis. There was also a significantly reduced rate constant for erythrocyte rubidium uptake in patients with undialysed chronic renal failure (0.66 h-1) and in those treated by haemodialysis (0.78 h-1), whereas in patients treated by continuous ambulatory peritoneal dialysis the rate constant for erythrocyte rubidium uptake was not significantly different from control values (1.36 h-1 and 1.41 h-1, respectively). 4. These findings are consistent with a reversal of the inhibition of erythrocyte Na+/K+ pump activity in vivo found in chronic renal failure by continuous ambulatory peritoneal dialysis, but not by haemodialysis. This difference may be due to the failure of haemodialysis to clear a circulating inhibitor of Na+, K(+)-ATPase or to the rapid re-accumulation of such an inhibitor after haemodialysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Dilated cardiomyopathy in haemophiliacs infected with the human immunodeficiency virus.

Infection with the human immunodeficiency virus (HIV) can result in several cardiac abnormalities including dilated cardiomyopathy. These phenomena have been described in people contracting the virus through sexual intercourse, injection drug use and by vertical transmission. We have identified recently two Scottish haemophiliacs who have developed dilated cardiomyopathy in the context of HIV infection acquired through treatment with contaminated factor VIII. The significance of this finding is discussed.

Adolescent

Early vasodilator treatment in myocardial infarction: appropriate for the majority or minority?

OBJECTIVE: To assess the influence of vasodilator treatment started early after myocardial infarction on left ventricular size and function. SETTING: Coronary care unit, Royal Infirmary, Edinburgh. PATIENTS: 105 patients with acute myocardial infarction (systolic blood pressure > 90 mm Hg) were randomised within 24 hours of the start of pain. Unlike previous studies 88% of the patients received thrombolysis. METHODS: Double blind randomised placebo controlled study with either 12.5 mg of captopril three times daily or 20 mg of isosorbide mononitrate three times daily for 28 days. MAIN OUTCOME MEASURES: Clinical outcome and left ventricular size and function assessed by echocardiography, radionuclide ventriculography, and magnetic resonance imaging. RESULTS: There was no difference in left ventricular size or function in either treatment group as measured one week after the end of the trial. Even the placebo group tended to decrease left ventricular diameter over the four week study period (one week: 5.0 (0.1) v, five weeks: 4.8 (0.1) cm, NS). Four patients had an adverse clinical outcome in the placebo group whereas no adverse outcome was seen in the captopril group. CONCLUSIONS: Vasodilator treatment may be of limited value or of no benefit for most infarct patients, particularly those treated with thrombolytic agents. Captopril, however, may benefit patients at high risk.

Captopril