Increased plasma levels of brain natriuretic peptide in patients with isolated diastolic dysfunction.
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Aged↗
Biomedical subjects
T M MacDonald
Publications and source records attributed to T M MacDonald.
Effects of angiotensin II and aldosterone on diastolic function in vivo in normal man.
1. Doppler echocardiographic indices of diastolic function and systemic haemodynamics were studied in response to infusions of angiotensin II (1, 2, 5 and 10 ng min-1 kg-1), D-aldosterone (2, 4, 10 and 20 ng min-1 kg-1) and placebo [0.9% (w/v) NaCl] in ten normal male subjects. 2. Dose-related increases in systolic and diastolic blood pressure were observed with angiotensin II infusion at rates of 2 ng min-1 kg-1 and above, whereas no changes in blood pressure occurred with D-aldosterone. No changes in aortic stroke distance or heart rate were seen with either angiotensin II or aldosterone infusion. 3. Compared with placebo, angiotensin II infusion produced a dose-related prolongation of the isovolumic relaxation time [mean and 95% confidence intervals 12.0 (8.2-15.8) ms, P < 0.001] at 10 ng min-1 kg-1, and a significant reduction in the ratio between early and late transmitral flow velocity integrals at 2 ng min-1 kg-1, [-0.84 (-1.63 to -0.05), P < 0.05] and 5 ng min-1 kg-1 [-0.76 (-1.47 to -0.05), P < 0.05]. No changes in Doppler echocardiographic indices of diastolic function were observed with D-aldosterone infusion. 4. These data suggest that angiotensin II, even at a sub-pressor concentration, produces an impairment of left ventricular diastolic filling, which occurs independently of its effect on aldosterone release.
Adult↗
The economic evaluation of antibiotic therapy: relevance to urinary tract infection.
Economic analyses of health care interventions can be performed with various levels of sophistication but all aid in decision-making processes which determine funding priorities. Pharmacoeconomics is the application of health economic techniques to the evaluation of drug therapy. In this article the pharmacoeconomic principles underlying the rational choice of an antibiotic for the treatment of urinary tract infections are discussed. Examples of pharmacoeconomic, adverse reaction and non-compliance studies are quoted to illustrate these principles. Efficacy and freedom from adverse effects are the principal determinants of favourable cost-effectiveness ratios, rather than antibiotic costs alone. Doctors should bear this in mind when choosing drugs to treat urinary tract infection.
Adolescent↗
Diastolic heart failure.
Diastolic heart disease is common and appears to be the primary abnormality in a substantial proportion of all patients with CHF. The epidemiology and natural history of the condition appears different to that of systolic heart failure, resulting in significant morbidity although contributing little to overall mortality. Clinical assessment alone is inadequate to distinguish systolic from diastolic failure, and echocardiography is an essential investigation in the management of these patients. From a therapeutic standpoint an alternative approach to treatment is likely to be indicated, and the results of recent major trials in systolic heart failure cannot necessarily be extrapolated to this group of patients.
Adrenergic beta-Antagonists↗
Left ventricular hypertrophy in hypertension--general and local trends in diagnosis and therapy.
LVH is a frequent echocardiographic finding in the general population but it should be regarded as an ominous predictor of future cardiovascular events rather than an innocent compensatory phenomenon. Echocardiography is the most sensitive and specific method for its detection but the ECG should not be regarded as superfluous since additional prognostic information and information about coexisting myocardial damage is present. The decreasing prevalence of LVH suggests that LVH can be prevented by control of hypertension and prevention of weight gain. Once LVH is present then antihypertensive drugs, weight reduction or salt restriction may promote its reversal, with early studies demonstrating associated improvement in mortality and morbidity.
Adult↗
The Tayside record linkage system.
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Adolescent↗
The relationship between blood pressure and left ventricular mass in essential hypertension is observed only in the presence of the angiotensin-converting enzyme gene deletion allele.
An insertion/deletion polymorphism in the angiotensin-converting enzyme (ACE) gene accounts for approximately 50% of the variance in plasma ACE concentration: deletion homozygotes (DD) have the highest, and insertion homozygotes (II) the lowest ACE concentrations. ACE is responsible for the generation of angiotensin II, which is implicated in the development of left ventricular hypertrophy, an independent risk factor for morbidity and mortality in hypertension. The aim of this study was to investigate the contribution of ACE genotype to the development of left ventricular hypertrophy in patients with essential hypertension. Eighty-five patients with essential hypertension underwent echocardiographic assessment of left ventricular mass index (LVMI) and determination of ACE genotype from leukocyte DNA by polymerase chain reaction. There was no significant difference in LVMI among the genotypes (II, ID, DD). Analysis of covariance modelled for LVMI showed a significant interaction with systolic blood pressure (p = 0.036) but not diastolic blood pressure (p = 0.453). The relationship between LVMI and systolic blood pressure was strongest in the deletion homozygotes (p = 0.002, R2 = 0.47), and also present in the heterozygotes (p = 0.013, R2 = 0.40). No relationship was seen in the insertion homozygotes (p = 0.914, R2 = 0.23). These findings suggest that the effect of blood pressure on LVMI in essential hypertension is expressed only in the presence of the ACE gene deletion allele.
Alleles↗
Primary non-compliance with prescribed medication in primary care.
OBJECTIVE: To determine the rate of patients not redeeming their prescriptions (primary noncompliance) and assess the factors influencing this. DESIGN: Observational study comparing copies of prescriptions written by general practitioners with those dispensed by pharmacists and subsequent case record review. SETTING: A large rural general practice in Tayside. SUBJECTS: All 4854 patients who received prescriptions (20,921) written between January 1989 and March 1989. MAIN OUTCOME MEASURES: The rate of non-redemption of prescriptions. RESULTS: Seven hundred and two patients (14.5%) did not redeem 1072 (5.2%) prescriptions during the study period, amounting to 11.5% of men and 16.3% of women. Non-redemption was highest in women aged 16-29 (27.6% of women) and men aged 40-49 (18.3% of men). Of prescriptions issued to women for oral contraceptives 24.8% were not redeemed during the study period. In those who redeemed prescriptions 17% were not exempt from prescription charges compared with 33% of patients who failed to redeem them. The non-redemption rate was highest for prescriptions issued at the weekends, although this was a small proportion of all prescribing. Prescriptions issued by trainee general practitioners were also less likely to be redeemed. CONCLUSIONS: Non-redemption varies with age, sex, general practitioner, exemption status, and with day of the week the prescription was written. Observational studies of drug exposure can be more accurately estimated from dispensing rather than prescribing data.
Adolescent↗
The risks of symptomatic vaginal candidiasis after oral antibiotic therapy.
It is generally accepted that antibiotic use can result in vaginal fungal overgrowth, although evidence estimating the extent to which this causes symptomatic vaginitis is scant. In a study using the prescription of vaginal antifungal preparations as a surrogate measure of vaginal candidiasis, a cohort of women taking antibiotics had a higher incidence of vaginal candidiasis after antibiotic exposure than beforehand (relative risk 2.3; 95% confidence interval 1.9-3.0); this risk was highest in those aged 36-40 years (RR 6.0, 95% CI 2.9-12.5). The attributable risk was highest among those who were taking cephalosporins (AR 12.8%, 95% CI 9.1-16.5). In a case-control study, comparing previous antibiotic exposure among women using vaginal antifungal agents and matched controls, antibiotic exposure was higher among those using vaginal antifungal agents during the previous 28 days, with an odds ratio of 5.5 (95% CI 3.8-7.9).
Administration, Oral↗
Echocardiography in chronic heart failure in the community.
A total of 128 patients from a single practice population who were receiving loop diuretics for treatment of presumptive cardiac failure were identified from prescribing data captured by the Medicines Monitoring Unit. A subgroup of 78 patients underwent echocardiography to determine the prevalence of true left ventricular systolic dysfunction in this population and the validity of the diagnosis of cardiac failure in primary care. A further 50 patients were studied to assess the workload generated by these patients for both primary health care and hospital services. The estimated prevalence of left ventricular systolic dysfunction was 0.84%, whereas 1.6% of the population received loop diuretics for this indication. A false-positive diagnosis occurred in 47% and was more likely in females (73%) than males (37%). Of all consultations 79% were seen by GPs, 14% as hospital out-patients and 7% as in-patients. Within the hospital general physicians have most contact with these patients. In summary chronic heart failure is common within the community, although the false-positive rate for diagnosis of this condition is high. GPs and general physicians treat the majority of these patients and should therefore receive continuing education regarding recent advances in this area. Echocardiography should be performed early in the management of all patients suspected of having cardiac failure.
Adult↗
Decreased cardiac parasympathetic activity in chronic heart failure and its relation to left ventricular function.
BACKGROUND: Activation of the sympathetic nervous system has been extensively studied in patients with chronic heart failure, but the parasympathetic nervous system has received relatively little attention. The objective in this study was to investigate cardiac parasympathetic activity in chronic heart failure and to explore its relation to left ventricular function. METHODS: Heart rate variability was measured from 24 hour ambulatory electrocardiograms by counting the number of times each RR interval exceeded the preceding RR interval by more than 50 ms (counts). This method provided a sensitive index of cardiac parasympathetic activity. RESULTS: Mean (range) of counts were: waking 48 (1-275)/h, sleeping 62 (0-360)/h, and total 1310 (31-7278)/24 h. These were lower than expected, and in 26 (60%) of the 43 patients counts fell below the lower 95% confidence intervals (95% CI) for RR counts in normal subjects. A significant correlation between total 24 hour RR counts and left ventricular ejection fraction was present (r = 0.49, p less than 0.05). CONCLUSIONS: These results indicate that most patients with chronic heart failure have reduced heart rate variability and therefore reduced cardiac parasympathetic activity. The degree of parasympathetic dysfunction is related to the severity of left ventricular dysfunction. This may be relevant to the high incidence of ventricular arrhythmias and poor prognosis of patients with chronic heart failure.
Adult↗
Caffeine restriction: effect on mild hypertension.
OBJECTIVE: To determine the effects on blood pressure of modifying dietary caffeine intake in patients with mild and borderline hypertension by monitoring ambulatory and clinic blood pressure. DESIGN: Four way, randomised, crossover trial of four consecutive two week dietary regimens: normal diet, caffeine free diet alone, caffeine free diet with decaffeinated instant coffee, caffeine free diet with caffeinated instant coffee (instant coffee phases conducted double blind). SETTING: Hospital hypertension clinic, Scotland. PATIENTS: 52 patients (23 men; aged 26-67 years) with untreated borderline or mild hypertension (diastolic blood pressure 90-105 mm Hg) who normally drank a minimum of three cups of coffee daily. MAIN OUTCOME MEASURES: Mean ambulatory blood pressure over 24 hours; mean morning, daytime, and night time ambulatory blood pressure; sitting clinic blood pressure at 1700; plasma caffeine concentration at 1700 on the last day of each regimen. RESULTS: Mean 24 hour ambulatory blood pressure was not different between regimens. There was no difference in blood pressure variability between regimens. During the caffeine free diet alone morning ambulatory diastolic blood pressure was higher (2.8 mm Hg) than during the caffeine free diet with caffeinated coffee. Mean sitting clinic systolic blood pressure was higher at 1700 (4.7 mm Hg) with a caffeine free diet than with the caffeine free diet with caffeinated coffee (p less than 0.05). Dietary compliance as assessed by plasma caffeine concentration was excellent. There was no significant correlation between plasma caffeine concentration and blood pressure. CONCLUSIONS: Drinking caffeinated instant coffee over a two week period does not adversely influence blood pressure in patients with borderline or mild hypertension; abstinence is of no benefit.
Adult↗
Metoclopramide, domperidone and dopamine in man: actions and interactions.
The effects of oral doses of the dopamine antagonist antiemetics metoclopramide and domperidone on baseline and dopamine stimulated renal function and systemic haemodynamics were assessed in a placebo controlled crossover study in 9 healthy volunteers. Metoclopramide did not change baseline ERPF, GFR or FF over 2 h post dosing but it significantly reduced baseline UNaV, UKV, urine flow, urinary dopamine excretion, supine and erect diastolic blood pressure and supine systolic blood pressure. Domperidone and placebo did not cause these effects. Metoclopramide caused a marked rise and domperidone a small fall in plasma aldosterone concentration (PAC) but placebo was without effect. Neither antiemetic altered plasma renin activity (PRA) but a small fall occurred with placebo. Two hours after pretreatment with placebo dopamine (2 micrograms/kg/min) increased effective renal plasma flow (ERPF), glomerular filtration rate (GFR), sodium excretion rate (UNaV), urine flow rate, urinary dopamine excretion rate, supine systolic blood pressure and supine and erect pulse rate and decreased the potassium excretion rate (UKV), filtration fraction (FF) and supine diastolic blood pressure. Metoclopramide pretreatment, did not attenuate the dopamine induced rise in ERPF, GFR, urine flow, urinary dopamine excretion or supine systolic blood pressure but it did attenuate the rise in pulse rate, the fall in diastolic pressure, and the antikaliuretic effect of dopamine leading to a net kaliuresis when compared to placebo. Domperidone was similar to placebo. Neither metoclopramide nor domperidone given orally caused clinically important antagonism of the renal haemodynamic effects of dopamine. However the effects of metoclopramide on blood pressure and electrolyte excretion may have clinical importance.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
A single dose study of the effects of fenoldopam and enalapril in mild hypertension.
To clarify the contribution made by the renin-angiotensin system activation to the short lived hypotensive response to fenoldopam, the haemodynamic effects of a combination of fenoldopam (100 mg) and enalapril (5 mg) were compared with fenoldopam alone, enalapril alone and placebo in a balanced, randomised, double blind, single dose study in eight hypertensive patients. Fenoldopam caused an acute fall in blood pressure which lasted approximately 3 h after dosing and was associated with a reflex tachycardia. Enalapril caused a more gradual fall in blood pressure (onset 2 h) without a reflex tachycardia. The combination of drugs produced greater reductions in blood pressure sustained for a longer period than fenoldopam alone and with a more rapid onset than enalapril alone. In combination the hypotensive effects of fenoldopam and enalapril were clearly additive and not synergistic. Activation of the renin-angiotensin system does not antagonise significantly the hypotensive effect of fenoldopam.
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
Disposition of gamma-glutamyl levodopa (gludopa) after intravenous bolus injection in healthy volunteers.
1. The pharmacokinetics of gludopa in healthy volunteers were studied at two doses, 250 micrograms kg-1 and 100 micrograms kg-1, after rapid intravenous bolus injection. 2. Gludopa had a clearance of 4.43 +/- 1.50 ml min-1 kg-1 and 4.92 ml min-1 kg-1 at the higher and lower doses, respectively. Corresponding half-lives were 29.2 +/- 3.7 min and 32.5 +/- 5.6 min, and volumes of distribution were 0.183 +/- 0.052 l kg-1 and 0.235 +/- 0.07/ l kg-1. 3. Urinary excretion of dopamine rose sharply after injection of gludopa at both doses, peaking at 30 min. At this time, amounts were over 215 and 60 times baseline values at the higher and lower dose of gludopa, respectively. Urinary dopamine rose in parallel with urinary levodopa excretion, supporting the view that levodopa is the precursor of urinary dopamine. 4. Less than 1% of the injected dose of gludopa was excreted unchanged in the urine. 5. These findings suggest that, in man, gludopa is an efficient pro-drug for dopamine. Gludopa may find therapeutic use in conditions where the beneficial renal effects of dopamine may be indicated.
Adult↗
Post-marketing drug surveillance--how far have we got?
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England↗
A preliminary study of the dopamine DA1 agonist fenoldopam in the treatment of chronic left ventricular failure due to ischaemic heart disease.
The effects of chronic oral fenoldopam in the treatment of NYHA grade II-III heart failure secondary to ischaemic heart disease, were studied in a placebo controlled, double blind, randomised, parallel group fashion in 20 patients. Nine patients taking placebo and six taking fenoldopam completed the study. Adverse events were similar in each group. There were no significant changes in exercise capacity, ejection fraction, body weight or symptom questionnaires with either treatment. This preliminary study has not revealed any benefit of fenoldopam in heart failure due to ischaemic heart disease.
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
Effect of prolonged intravenous infusion of gludopa in humans and a preliminary study of its oral bioavailability.
Intravenous infusion of gamma-glutamyl-L-dopa (25 micrograms/kg/min) for 10 h in normal humans caused a natriuresis of 46.5 mmol of sodium without an increase in plasma renin activity and was associated with small but significant falls in blood pressure. In a second study the oral bioavailability of gludopa was estimated in normal subjects and found to be low (less than 2%). The increase in urine dopamine excretion and the natriuretic effect of gludopa were much larger after intravenous infusion than oral dosing.
Absorption↗