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Biomedical subjects

C A Howie

Publications and source records attributed to C A Howie.

At least 37 records · Page 2Linked to original sources
PubMed1992

Dialysis at home in the west of Scotland: a comparison of hemodialysis and continuous ambulatory peritoneal dialysis in age- and sex-matched controls.

OBJECTIVE: To audit the outcome of patients treated at home by hemodialysis and continuous ambulatory peritoneal dialysis (CAPD). DESIGN: Retrospective comparison of nondiabetic hemodialysis patients with age- and sex-matched nondiabetic patients treated by CAPD. SETTING: Renal Units, Stobhill General Hospital and Western Infirmary, Glasgow, providing the home dialysis service for the West of Scotland. PATIENTS: Between 1982 and 1988, 139 hemodialysis patients starting treatment at home, compared with 139 matched patients starting CAPD over the same time period. MAIN OUTCOME MEASURES: Patient characteristics and cardiovascular risk factors at the start of home treatment. Patient and technique survival with both forms of dialysis. RESULTS: Patients selected for home hemodialysis were less likely to be smokers (p < 0.02) and to have electrocardiographic evidence of ischemia or left ventricular hypertrophy (p < 0.05) than patients treated by CAPD. Patient survival and technique survival (excluding death and renal transplantation) at 3 years were 93.8% versus 86.2% (p < 0.05) and 94.2% versus 80.8% (p < 0.04) for hemodialysis and CAPD, respectively. Cardiovascular events were responsible for the majority of deaths in both groups, but there was a greater proportion of deaths from other causes in patients treated by CAPD. There was no significant difference in the transplantation rate between the two treatment groups. CONCLUSIONS: Home dialysis is an effective method of renal replacement treatment for patients with end-stage renal disease. The results of hemodialysis are superior to CAPD, but this may be partly due to selection bias.

Actuarial Analysis↗
PubMed1991

A dose-ranging study of UK-68,798, a novel class III anti-arrhythmic agent, in normal volunteers.

1. UK-68,798, a novel class III anti-arrhythmic agent was administered intravenously to twelve healthy volunteers in a placebo controlled, double-blind, dose-escalating study. 2. Doses of 5 and 10 micrograms kg-1 of UK-68,798 selectively and significantly prolonged the QT interval, with mean maximum changes of 35 and 107 ms respectively, without affecting other ECG intervals. 3. There were dose-related increases in AUC but clearance (23 l h-1), terminal elimination half-life (8 h) and volume of distribution (245 l) were found to be independent of dose with low levels of intra- and inter-patient variability. 4. UK-68,798 has electrophysiological effects indicative of selective class III anti-arrhythmic activity and merits further assessment in clinical studies.

Adult↗
PubMed1991

The effects of age on the pharmacokinetics, antihypertensive efficacy and general tolerability of dilevalol.

1. This study investigated the influence of age on the pharmacokinetics, pharmacodynamics, general tolerability and concentration-effect relationships in 18 patients with essential hypertension (age range 23-73 years) during treatment with dilevalol, a non selective beta-adrenoceptor antagonist with vasodilator properties. 2. There were no significant age-related changes in pharmacokinetics for either acute or chronic treatment with dilevalol, although there were significant changes in elimination half-life from 7.8 to 11.7 h (P less than 0.05) and in AUC from 261 to 352 ng ml-1 h (P less than 0.005) following translation from acute to chronic dosing. 3. In absolute terms, dilevalol treatment (as compared with placebo) produced numerically larger falls in average blood pressure in the six oldest as compared with the six youngest patients: for example, supine blood pressure fell by, respectively, 29/15 and 10/7 mm Hg during chronic treatment. 4. Using an integrated kinetic-dynamic model, blood pressure responsiveness was characterised by relating the fall in blood pressure (mmHg) to the plasma drug concentrations in each individual patient. No independent age-related effect was demonstrated. There was a significant relationship between response and the height of initial blood pressure which tended to be higher in the elderly patients. 5. Patient tolerability was generally satisfactory and there was no differential age-related effect. 6. This study has shown that the antihypertensive efficacy of dilevalol is not attenuated in the elderly and that there are no significant age-related differences in pharmacokinetics or pharmacodynamics.

Adult↗
PubMed1991

Studies with abanoquil (UK-52,046) a novel quinoline alpha 1-adrenoceptor antagonist: I. Effects on blood pressure, heart rate and pressor responsiveness in normotensive subjects.

1. Abanoquil (UK 52,046) is a novel, quinoline-derivative, alpha 1-adrenoceptor antagonist which, on the basis of animal studies, possesses antiarrhythmic activity at doses which have little or no effect on blood pressure. 2. In two placebo-controlled, double-blind, crossover studies the alpha 1-adrenoceptor antagonist activity (phenylephrine pressor responses) and the effects on blood pressure and heart rate (in the presence and absence of concomitant beta-adrenoceptor blockade) have been investigated in healthy, normotensive subjects following the intravenous administration (i.v.) of abanoquil. 3. In the first study, abanoquil at a dose of 0.4 micrograms kg-1 i.v. (as a bolus or by increments) produced significant alpha 1-adrenoceptor antagonism (with rightward shifts of more than two-fold in the phenylephrine pressor dose-response curves) but no significant effects on supine or erect blood pressure and heart rate. 4. In the second study, a dose of 0.5 micrograms kg-1 i.v. had no significant effect on supine or erect blood pressure but pre-treatment with atenolol promoted a small fall in erect blood pressure without causing significant orthostatic hypotension. 5. In conclusion, significant alpha 1-adrenoceptor antagonism without marked reflex tachycardia or profound postural hypotension suggest that abanoquil has a different haemodynamic profile from that of 'classical' peripheral alpha 1-adrenoceptor antagonists.

Adrenergic alpha-Antagonists↗
PubMed1990

Psychological disturbance in children with haemophilia.

OBJECTIVE: To assess the need for formal psychotherapeutic intervention in children attending a children's haemophilia clinic after some of them had been diagnosed as positive for HIV. DESIGN: Comparison of haemophiliac children with matched control groups of diabetic and healthy children. SETTING: The West of Scotland Children's Haemophilia Centre, Glasgow. PATIENTS: 43 Children aged 3 to 16 years with mild, moderate, and severe clotting disorders were matched with control groups of 46 diabetic children and 42 physically healthy children. INTERVENTIONS: Parents of children aged 3-5 years were interviewed with the behaviour screening questionnaire. Children aged 6 to 16 were assessed by parental and teacher report using standardised questionnaires and self report using a computerised depression inventory. All were scored numerically according to the presence of symptoms of emotional and behavioural problems. MAIN OUTCOME MEASURES: The groups were compared for mean scores on each rating device and for number of children achieving scores within the pathological range. RESULTS: In the 6-16 age group five haemophiliac children, five diabetic children, and three healthy children scored in the pathological range on the parent questionnaire, as did two, three, and five respectively on the teacher questionnaire and four, four, and eight on the depression inventory. There was no significant difference across the three groups. Analysis of mean scores similarly showed no significant difference across groups. In contrast, the single measure used for younger children showed an increase in behavioural difficulties among the diabetic children. CONCLUSION: Haemophiliac children attending the West of Scotland Centre were no more disturbed than their diabetic or healthy peers despite the identification of HIV infection within the clinic and the widespread adverse publicity associated with AIDS and HIV infection.

Adolescent↗
PubMed1990

Umbilical artery blood velocity waveform analysis in predicting the small-for-dates fetus.

Doppler umbilical artery blood velocity waveforms were recorded longitudinally in 78 randomly selected pregnancies. The waveform maximal (A) to minimal (B) Doppler shift frequency ratios were determined to provide a semi-quantitative measure of impedance to blood flow in the fetoplacental circulation. Fifty-eight of these pregnancies and their outcomes were normal. The A/B ratios from this normal group were used to derive a normal range of this index throughout the second half of pregnancy. A further 45 pregnancies, also randomly selected, were studied once within 2 weeks of delivery. Using those measurements, plus those from the longitudinal groups sampled within 2 weeks of delivery, the predictive values of the A/B ratio in detecting the small for gestational age fetus have been derived. The sensitivity of the umbilical artery A/B ratio in predicting a small for gestational age infant within 2 weeks of delivery was 58% with a specificity of 94%. The positive test predictive value was 69% with a negative test predictive value of 90%. These predictive values are lower than those previously published, probably because high-risk pregnancies were over-represented in earlier studies. Waveform analysis within 2 weeks of delivery did, however, appear to identify fetuses destined to develop a range of perinatal problems. Large prospective studies are needed before the predictive value of Doppler waveform analysis is clarified.

Blood Flow Velocity↗
PubMed1990

Awareness among pregnant women of the effect on the fetus of commonly used drugs.

Epidemiological studies have shown that pregnant women continue to take substantial quantities of drugs, particularly those readily available to them without prescription. Little is known of the attitudes and knowledge among pregnant women of the effects of these substances on the fetus. Awareness of the effects on the fetus of commonly used drugs, cigarettes and alcohol among 514 women in the postnatal wards of two maternity units in Glasgow was assessed by self completion questionnaire between October 1987 and April 1988. Most of the women recognised that the fetus is most at risk of being harmed by drugs during the first 3 months of pregnancy. The majority felt it was safest not to smoke cigarettes and were aware of the adverse effects of smoking on fetal growth. Over half thought smoking was harmful while breastfeeding. Over half thought that alcohol should be avoided altogether in pregnancy and that drinking could harm the fetus. Most women considered alcohol harmful to the breast feeding baby. The majority of the women would opt for paracetamol containing analgesics only and only a small proportion would take one containing aspirin. Only half the study population would take a prescribed antibiotic. A generally high level of awareness of commonly used drugs was demonstrated although there are areas where further health education could be directed. The study has highlighted areas worthy of further research.

Adolescent↗
PubMed1990

Prediction of the antihypertensive response to enalapril.

This study investigates the potential utility of a drug concentration-effect modelling approach to predict the long-term response to antihypertensive treatment with enalapril. Concentration-effect relationships were characterized in 13 subjects following a single dose of enalapril (20 mg) and for each individual the derived parameters were used to predict the steady-state blood pressure profile. The predicted responses (before dosing and 4 h after dosing) were in close agreement with the responses observed after 6 weeks. In individual patients, the observed and predicted blood pressure profiles over a 12 h period were compared. In six of the 13 subjects, there were statistically significant (P less than 0.05) prediction errors. However, in all but one of these patients the error was less than 10%, and for the group as a whole the mean prediction error was small and not statistically significant (-0.6 +/- 2.1 mmHg). The kinetic-dynamic parameters derived from observations of the first dose were used to simulate steady-state responses to several alternative doses and dose frequencies. A regimen of 10 mg twice daily increased the ratio of blood pressure at trough-to-peak response to 75 +/- 5% compared to 33 +/- 16% when 20 mg was given once daily. In addition, a twice-daily regimen reduced the coefficient of variation of the hourly average blood pressure. Thus, concentration-effect parameters derived from the first dose response to enalapril have potential not only for predicting long-term antihypertensive response, but also for optimizing dosage regimens for individual patients.

Blood Pressure↗
PubMed1990

Vascular pressor responses in treated and untreated essential hypertension.

Thirty-seven essential hypertensives received placebo for 3 weeks followed by nifedipine retard (n = 14) or enalapril (n = 13) or doxazosin (n = 10) as monotherapy for 6 weeks and attended study days to evaluate the effects of placebo, first dose, and chronic (1-6 weeks) treatment. On each study day, pressor responses to i.v. infusions of phenylephrine (PE) and angiotensin II (AII) were measured 1.5-3 h after drug administration and the derived PD20 values (dose required to increase mean blood pressure by 20 mm Hg) compared. Each treatment produced comparable reductions in BP. Nifedipine significantly attenuated the pressor responses to AII and PE: for AII, the mean PD20 (ng/kg/min) increased from 8.2 (placebo) to 9.9 (first dose), 13.9 (1 week), and 17.4 (6 weeks). Pressor responsiveness to both AII and PE was unchanged following enalapril: for PE, the mean PD20 (micrograms/kg/min) was 2.1 (placebo), 1.5 (first dose), and 1.5 (6 weeks). Doxazosin produced rightward shifts of the PE pressor dose-response curves but had no effect on responses to AII. The relationship between the simultaneous BP and HR changes during the infusion of PE was used as an index of cardiac baroreflex activity. In contrast to enalapril and doxazosin, which had no effect, nifedipine reduced the slope of the HR/BP relationship from -0.62 (placebo) to -0.38 (first dose) and -0.31 beats/min/mm Hg (6 weeks). For comparable reductions in BP, doxazosin only affects adrenergic mechanisms whereas nifedipine affects both adrenergic and non-adrenergically mediated vasoconstriction. The ACE inhibitor enalapril had no effect on pressor responses to AII and PE.

Adult↗
PubMed1990

An evaluation of the alpha-adrenoceptor antagonism produced by SK&F 86466 in healthy normotensive males.

SK&F 86466 is a novel, potent alpha-adrenoceptor antagonist which, in animal experiments, is reported to show a high selectivity for alpha 2-adrenoceptors at both pre- and post-junctional sites. The effects of two intravenous doses of 80 and 200 micrograms kg-1 of SK&F 86466 were assessed in a placebo-controlled, double-blind, randomised study in eight young, healthy, normotensive males. Two indices of alpha-adrenoceptor activity were investigated: i) Pressor responsiveness to the relatively selective alpha 1-adrenoceptor agonist phenylephrine and to the preferential alpha 2-adrenoceptor agonist alpha-methylnoradrenaline. ii) Circulating levels of noradrenaline. SK&F 86466 at a dose of 200 micrograms kg-1 produced rightward shifts of the pressor dose-response curves to both agonists: a 1.4 fold shift for phenylephrine (P = 0.023) and a 1.6 fold shift for alpha-methylnoradrenaline (P = 0.051). Erect plasma noradrenaline sampled at 105 min into the infusion was significantly increased from 2.9 to 5.0 nmol l-1 by SK&F 86466 200 micrograms kg-1 (P = 0.002). The change in the phenylephrine responses indicates post-junctional alpha 1-adrenoceptor blockade and the rise in noradrenaline is consistent with pre-junctional alpha 2-adrenoceptor antagonist activity. Overall the results of this study suggest that SK&F 86466, at a dose of 200 micrograms kg-1, causes both alpha 1- and alpha 2-adrenoceptor antagonism in human subjects.

Adrenergic alpha-Antagonists↗
PubMed1990

Desensitization and down-regulation of brain alpha 2-adrenoceptors by centrally acting antihypertensive drugs.

Rabbits were treated with intravenous clonidine (8 mumol kg-1 day-1), guanabenz (20 mumol kg-1 day-1), rilmenidine (80 mumol kg-1 day-1) or vehicle via osmotic minipumps. After 6 days treatment mean arterial pressure (MAP), pressor responses to intravenous alpha-methyl noradrenaline and depressor responses to intracisternal clonidine were studied, and [3H]-yohimbine binding to forebrain and hindbrain examined in vitro. Clonidine, guanabenz and rilmenidine had similar effects on MAP and caused a similar attenuation of the depressor response to intracisternal clonidine, but only guanabenz attenuated pressor responses to intravenous alpha-methyl noradrenaline. Rilmenidine had no effect on [3H]-yohimbine binding to brain membranes. Clonidine treatment decreased binding in hindbrain while guanabenz treatment decreased binding in both fore- and hindbrain. Thus, the depressor effects of chronic treatment did not correlate with the effects on [3H]-yohimbine binding sites in rabbit brain suggesting that the blood pressure lowering effects of many centrally acting antihypertensive drugs are not necessarily dependent on binding to the alpha 2-adrenoceptor site labelled by [3H]-yohimbine.

Animals↗
PubMed1990

First-choice antihypertensive drug use in the Glasgow Blood Pressure Clinic.

The evolution of antihypertensive drug use in the Glasgow Blood Pressure Clinic between 1969 and 1986 was determined, from computerized data, by extracting percentages of new patients prescribed different drugs at their first clinic visit. Prescribing of adrenergic neuron blockers and centrally acting drugs (methyldopa and clonidine) was common in the early years but declined rapidly until, after 1975 and 1980, respectively, it remained at 10% or less. Diuretics, mainly thiazides, were prescribed for 20% of patients in 1969 to a peak of 55% in 1980. beta-Blockers were first used during the early 1970s and their use peaked in 1980, when they were prescribed for over 60% of new patients. They remained a first-choice treatment in more than 40% of patients. Calcium channel blockers were first used in 1980 and by 1986 were prescribed for 15% of new patients. Angiotensin-converting enzyme inhibitors were used from 1982 and in 1986 were prescribed for 7% of new patients. These two classes of drugs are more expensive than older drugs. However, because of their low usage, this did not greatly influence treatment costs up to 1986, as beta-blockers and thiazides remained widely used.

Adrenergic beta-Antagonists↗
PubMed1989

Effects of short-term exposure to noradrenaline and adrenaline on adrenoceptor responses.

Adrenaline (0.05 and 1.5 mumol/kg per h) and noradrenaline (0.09 and 0.5 mumol/kg per h) were infused i.v. into conscious rabbits. Pressor responses to bolus doses of phenylephrine, alpha-methylnoradrenaline and chronotropic responses to isoprenaline were studied before and during infusion. Plasma adrenaline levels rose from 1.4 +/- 0.5 to 13 +/- 2 and 31 +/- 9 nM during the 0.05 and 1.5 mumol/kg per h infusions respectively while noradrenaline levels rose from 2.0 +/- 0.9 to 16 +/- 7 and 29 +/- 11 nM during the 0.09 and 0.5 mumol/kg per h noradrenaline infusions. Pressor responses to alpha-methylnoradrenaline were attenuated within 2.5 and 60 min during the higher and lower rates of adrenaline infusion respectively. Attenuation occurred within 10 min with the higher rate infusion of noradrenaline but no change was seen during the lower noradrenaline infusion. Chronotropic responses to isoprenaline were also reduced during the adrenaline infusions but not during noradrenaline infusion. In contrast no change was observed in phenylephrine pressor responses. These results suggest that short-term elevation in the levels of the endogenous catecholamines, noradrenaline and adrenaline, can cause desensitisation of alpha 2- and beta-adrenoceptors but not of alpha 1-adrenoceptors.

Animals↗
PubMed1989

Pressor responsiveness, age and hypertension.

It has long been accepted that enhanced vascular reactivity is an integral part of the hypertensive state. This study investigates pressor responsiveness to the selective alpha 1-adrenoceptor agonist, phenylephrine, in 62 normotensive and hypertensive subjects aged 20-70 years. Since blood pressure increases with age, it is possible that effects attributed specifically to blood pressure will be confounded by age. The present study showed no correlation between responsiveness and starting blood pressure. However, responsiveness was positively correlated with age. These results suggest that it may be an oversimplification to attribute increased vascular responsiveness to the hypertensive state.

Adult↗
PubMed1989

Hypercholesterolaemia in treated hypertensives: a controlled trial of intensive dietary advice.

We evaluated dietary counselling by dietitians in hypercholesterolaemic hypertensives over 6 months. A total of 141 patients were randomly assigned to intensive advice or usual care. Body weight fell significantly in the intervention group, but did not in the controls. There was a modest but significant fall in total cholesterol from 7.1 to 6.8 and 7.1 to 6.9 mmol/l in the diet and the control groups, respectively (4 and 3%). A similar pattern emerged from the triglyceride measurements. Low-density lipoprotein fell in both groups, but only achieved significance (P less than 0.05) in the intervention group. High-density lipoprotein did not change. There was a more marked change in cholesterol when serum levels during the study were compared with the previous annual review. These falls occurred after selection for the study but before random allocation to groups. They are unlikely to reflect regression to the mean as the lipids were stable for 2 or more years before the study, but may reflect spontaneous changes in diet after the patients were labelled hypercholesterolaemic. Dietary advice can lower total cholesterol but the magnitude of this decrease is small. Additional approaches are likely to be required to reduce plasma cholesterol to a normal range.

Antihypertensive Agents↗
PubMed1989

Lipoprotein and apolipoprotein levels in postmenopausal women on continuous oestrogen/progestogen therapy.

Levels of serum lipoproteins and apolipoproteins were monitored for 48 weeks in two groups of women taking part in a double-blind trial of continuous oestrogen/progestogen with and without oestriol. There were no differences between the effects of the two treatments on the substances measured. Triglycerides did not change and there was a transient fall in very low density lipoprotein cholesterol. Low density lipoprotein cholesterol fell over the first 24 weeks but rose thereafter to pretreatment levels. There was a decrease in high density lipoprotein (HDL) cholesterol due to a transient fall in HDL2 cholesterol and a gradual decrease in HDL3 cholesterol. Consequently, the only change in lipid levels present after 48 weeks was a decrease in HDL3 cholesterol, the clinical significance of which is uncertain. There was, however, an increase in apoprotein B levels and decreases in apoprotein AI and AII levels. These alterations in apoprotein levels may be unfavourable, since apoprotein B levels have been positively correlated and apoprotein AI and AII levels negatively correlated with coronary heart disease.

Apolipoproteins↗
PubMed1989

The effect of intravascular transfusion for rhesus haemolytic disease on umbilical artery Doppler flow velocity waveforms.

To test the hypothesis that an increase in fetal blood viscosity is associated with an increase in resistance to flow, the effect on Doppler flow velocity waveforms of percutaneous umbilical blood sampling and intravascular transfusion was studied in 20 patients undergoing a total of 35 procedures. All but four of the 22 transfusions were associated with a decrease in resistance to flow, as shown by a reduction in the umbilical artery systolic/diastolic ratio, and this also occurred on 10 of the 13 occasions when blood sampling only was performed. These findings suggest that acute changes in blood viscosity following intravascular transfusion are not associated with an increase in resistance to flow as assessed by Doppler velocimetry. Umbilical blood sampling per se may be associated with a humorally mediated reduction in placental vascular resistance to flow.

Blood Transfusion, Intrauterine↗