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Biomedical subjects

T M MacDonald

Publications and source records attributed to T M MacDonald.

At least 127 records · Page 7Linked to original sources
PubMed1996

Tolerability of topical NSAIDs in the elderly: do they really convey a safety advantage?

Nonsteroidal anti-inflammatory drugs (NSAIDs) are very widely prescribed but they have a poor tolerability profile, with a range of potential adverse effects. NSAIDs that are used in topical formulations have been developed in the past 15 years and their use is increasing. The purpose is to achieve a high local concentration of the active ingredient at the affected site, with as low a plasma concentration as possible to minimise possible systemic adverse effects. The gastrointestinal and renal toxicity of topical NSAIDs has recently been highlighted in the medical literature. The elderly seem to be more sensitive to the adverse effects of NSAIDs than younger individuals, and this may also be true for topical NSAIDs. More formal epidemiological evaluation of the safety of topical NSAIDs is required in the postmarketing situation, as the main source of information regarding adverse drug reactions to topical NSAIDs in the UK has been spontaneous reporting data.

Administration, Topical↗
PubMed1996

Potentially hazardous co-prescribing of beta-adrenoceptor antagonists and agonists in the community.

AIM: The aim of this study was to investigate the co-prescribing of beta-antagonists and beta-agonists in the community, and to assess the potential hazards of such co-prescribing. METHODS: The study was set in the population of Tayside, Scotland (population approximately 400,000), between January 1993 and March 1993. An automated person-specific prescribing database was used, which could also be linked to hospital admissions. Patients who were co-prescribed beta-antagonists and beta-agonists on the same day or within 30 days were selected. A model was used to identify those who showed an asthmatic profile, on the basis of age, and previous prescribing and hospitalization history, and for whom the co-prescribing was judged to be particularly hazardous. RESULTS: Altogether, 0.9% of 15824 patients who received a beta-antagonist during the study period received a beta-agonist on the same day. This figure increased to 274 (1.7%) for 30-day co-prescription. A few instances of particularly hazardous co-prescribing were identified, which involved young people who had previously received prescriptions for corticosteroids and been hospitalized for asthma. CONCLUSION: Potentially hazardous co-prescribing of beta-agonists and beta-antagonists occurs despite labelled warnings, even in patients who appear to be at high risk. These events are quite rare but probably should not occur at all.

Adrenergic beta-Agonists↗
PubMed1996

Indomethacin does not attenuate the hypotensive effect of trandolapril.

This is a randomised, double-blind, placebo-controlled, four-way crossover study to determine if indomethacin attenuates the hypotensive effect of trandolapril. Twenty-three hypertensive patients (diastolic blood pressure (DBP) 95-115) requiring NSAID were recruited. Seventeen completed the study. Three week treatment periods: trandolapril 2 mg od and indomethacin 25 mg tds, trandolapril 2 mg and placebo, indomethacin and placebo, placebo and placebo. Clinic and ambulatory BP after 3 weeks of each treatment. Study had 85% power to detect a 5 mm Hg difference in BP (s.d. 7 mm Hg). End of treatment clinic BPs were: 152.9/98 mm Hg (95% CI 147.2, 158.6/95.8, 101.4) with placebo and placebo; 150.4/94.9 mm Hg (95% CI 144.7, 156.1/92.1, 97.7) with trandolapril and indomethacin; 148.2/96.5 mm Hg (95% CI 142.5, 153.9/93.7, 99.3) with trandolapril and placebo; and 156.6/97.4 mm Hg (95% CI 150.9, 162.3/94.6, 100.2) with indomethacin and placebo. There were no significant interactions between trandolapril and indomethacin for clinic systolic BP (SBP) (P = 0.79) or clinic DBP (P = 0.87). When trandolapril treatments (placebo or with indomethacin) were compared to treatments without trandolapril (placebo or indomethacin), trandolapril lowered clinic SBP by 5.4 mm Hg (P = 0.047) and DBP by 2.3 mm Hg (P = 0.08). Mean ambulatory BP was: 140.6/88.2 mm Hg (trandolapril and placebo); 142.8/89.7 mm Hg (trandolapril and indomethacin); 149.6/95.0 mm Hg, (indomethacin and placebo); 147.7/94.0 mm Hg (placebo and placebo). Compared with placebo, trandolapril and placebo lowered BP by 6.5/7.5 mm Hg (P < 0.001, SBP; P < 0.001, DBP). Compared with indomethacin, trandolapril and indomethacin lowered BP by 5.0/5.5 mm Hg (P = 0.001, SBP; P < 0.001, DBP). In the present study trandolapril 2 mg lowered clinic SBP and ambulatory BP, but indomethacin did not attenuate this. Indomethacin had no significant effect on either clinic or ambulatory BP. The antihypertensive effects of trandolapril in this study were modest. Patient selection factors may have contributed to the observed responses, but it seems unlikely from these data that a clinically important drug interaction has occurred.

Adult↗
PubMed1995

Topical non-steroidal anti-inflammatory drugs and admission to hospital for upper gastrointestinal bleeding and perforation: a record linkage case-control study.

OBJECTIVE: To evaluate the relation between topically applied non-steroidal anti-inflammatory drugs and upper gastrointestinal bleeding and perforation. DESIGN: A case-control study with 1103 patients admitted to hospital for upper gastrointestinal bleeding or perforation between January 1990 and December 1992 (cases). Two different control groups were used, with six community controls and with two hospital controls for each case. Previous exposure to topical and oral non-steroidal anti-inflammatory drugs and ulcer healing drugs was assessed. STUDY POPULATION: The population of 319,465 people who were resident in Tayside and were registered with a Tayside general practitioner between January 1989 and October 1994. A record linkage database containing all data on hospital events and dispensed drugs between 1989 and 1992 was used for this population. MAIN OUTCOME MEASURES: Unadjusted and adjusted odds ratios of exposure in those admitted to hospital compared with controls. RESULTS: Significant unadjusted associations were detected between all three classes of drug and upper gastrointestinal complications. The significant association detected for topical non-steroidal anti-inflammatory drugs was no longer evident in analyses which adjusted for the confounding effect of concomitant exposure to oral anti-inflammatories and ulcer healing drugs (odds ratio = 1.45; 95% confidence interval 0.84 to 2.50 with community controls; 1.06; 0.60 to 1.88 with hospital controls). CONCLUSION: In this study topical non-steroidal anti-inflammatory drugs were not significantly associated with upper gastrointestinal bleeding and perforation after adjustment for the confounding effects of concomitant use of oral anti-inflammatories and ulcer healing drugs.

Administration, Oral↗
PubMed1995

Brain natriuretic peptide: effect on left ventricular filling patterns in healthy subjects.

1. Elevated plasma concentrations of brain natriuretic peptide are found in conditions associated with impaired left ventricular diastolic function. The purpose of this study was to determine whether this peptide actually plays a physiological role in improving myocardial performance in diastole. 2. Nine normal subjects received infusions of brain natriuretic peptide or placebo in a randomized, double-blind, crossover study. Brain natriuretic peptide infusion produced a significant reduction in isovolumic relaxation time (means and 95% confidence interval for difference -10.8 ms, -14.5 to -7.0 ms) (P < 0.01) and significantly increased both the peak E/A velocity (0.54, 0.14-0.94) (P < 0.05) and the E/A time velocity integral (1.09, 0.20-1.98) (P < 0.05). 3. These responses were evident at concentrations of brain natriuretic peptide that produced no associated effects on blood pressure, heart rate or stroke distance. 4. Brain natriuretic peptide infusion in normal subjects significantly reduces isovolumic relaxation time and improves transmitral Doppler flow profiles, suggesting that this peptide may be important in the control of left ventricular diastolic relaxation in man.

Cross-Over Studies↗
PubMed1995

The utilisation and economic evaluation of antibiotics prescribed in primary care.

This was an observational study of efficacy and resource utilisation over three years in a cohort of 917 patients who received at least one prescription for an oral antibiotic between January and March 1989 in a large rural primary care health centre in Tayside, Scotland. Three thousand, six hundred and sixty three prescriptions were issued (2286 to females) for; 1502 upper respiratory tract infections, 419 lower respiratory tract infections, 441 urinary tract infections, 177 skin and soft tissue infections, 97 gynaecological infections, 103 cases of acne and 71 other infections. Excluding acne, 14% of infections required more than one antibiotic to achieve a successful outcome. The highest success rates for antibiotics were amoxycillin (92%) and penicillin V (92%) in upper respiratory tract infections, erythromycin (90%) in lower respiratory tract infections and co-trimoxazole (83%) in urinary tract infections. The most cost-effective antibiotics were penicillin V for upper respiratory tract infection, erythromycin for lower respiratory tract infection and co-trimoxazole for urinary tract infection. Varying the value placed on general practitioners' time did not change the rank order of antibiotic cost-effectiveness. The efficacy and cost-effectiveness of the treatment of acute infections in primary care varies considerably with the antibiotic used as first choice. More expensive antibiotics might be justified in cost-effectiveness terms if they had high cure rates in clinical practice.

Adolescent↗
PubMed1995

Acute effects of atrial natriuretic peptide on left ventricular diastolic function. a pulsed wave Doppler study in man.

Doppler echocardiographic indices of diastolic function and systemic haemodynamics were studied in response to infusions of atrial natriuretic peptide (0.5, 1, 2, 5 pmol.kg-1.min-1) and placebo (0.9% (w/v) saline) in ten normal male subjects. Compared with placebo, atrial natriuretic peptide infusion produced a significant and dose-related reduction in the isovolumic relaxation time [(mean and 95% CI) -5.9 (-9.2 to -2.6) ms (P < 0.01) at 5 pg.kg-1 min-1] and a significant increase in the ratio between early and late transmitral peak velocities [0.46 (0.02 to 0.89) (P < 0.05) at 5 pg.kg-1 min-1]. No significant changes in heart rate, blood pressure or aortic stroke distance were observed with infusion of atrial natriuretic peptide compared with placebo. These data suggest that pathophysiological plasma concentrations of atrial natriuretic peptide improve diastolic function by increasing the rate of myocardial relaxation.

Adolescent↗
PubMed1995

Influence of basal nitric oxide secretion on cardiac function in man.

1. Nitric oxide is recognised as an important biological mediator, which is thought to be involved in cardiovascular homeostasis. The purpose of this study was to investigate the effects of basal nitric oxide synthesis on cardiac function in man, by blocking nitric oxide synthesis with NG-monomethyl-L-arginine (L-NMMA). 2. Eight normal volunteers were studied on two separate occasions. Measurements of heart rate, blood pressure and echocardiographic indices of left ventricular systolic and diastolic function were made at baseline on each day and every 20 min during incremental infusion of L-NMMA (0.1, 0.2, 0.5, 1.0 and 2.0 mg kg-1 h-1) or placebo. 3. A trend towards reduction in heart rate was observed with L-NMMA infusion although this did not reach statistical significance, whereas significant increases in both systolic blood pressure (at 2.0 mg kg-1 h-1) and systemic vascular resistance index (at 0.5 mg kg-1 h-1) were seen. 4. L-NMMA infusion caused significant reductions in stroke distance and cardiac index, although there was no change in the ratio of end systolic wall stress/end systolic volume index (an afterload independent index of left ventricular systolic performance). 5. The isovolumic relaxation time significantly increased with L-NMMA infusion, together with a significant reduction in the 'E' wave flow velocity integral. Reductions in both peak E/A ratio and E/A flow velocity integral ratio were also seen, although these failed to reach statistical significance. 6. In conclusion, the basal generation of nitric oxide in man appears to maintain a vasodilated state, and modifies left ventricular diastolic filling parameters.

Adult↗
PubMed1995

Left atrial size and function: assessment using echocardiographic automatic boundary detection.

OBJECTIVE: To evaluate the waveforms of left atrial area changes obtained by automated boundary detection with newly developed acoustic quantification technology. DESIGN: All subjects had measurements of left atrial areas taken in the apical four chamber, parasternal long axis, and parasternal short axis views using both conventional echocardiographic methods and automatic boundary detection on two occasions separated by at least a week. On the second visit measurements were also repeated in healthy volunteers after acute intravenous volume loading with 1 litre of saline over 2-5 minutes. SETTING: A university medical school echocardiographic laboratory. SUBJECTS: 12 healthy male volunteers and 8 patients with cardiac disease (5 with congestive heart failure, 1 with mitral stenosis, and 2 with hypertensive left ventricular hypertrophy, and dilated left atria). RESULTS: There was close correlation between conventionally derived left atrial areas and those obtained by automatic boundary detection, particularly in the apical four chamber view (r = 0.98). Both inter and intra observer variabilities (coefficient of variation) for left atrial areas measured by automatic boundary detection were good (4.7-14.2% and 8.1-18.6% respectively). The reproducibility (coefficient of variation) for derived indices of left atrial function, however, was much poorer (10.4-104.8% and 12.5-88% respectively). After acute volume loading significant increases in left atrial area were observed at all stages in the cardiac cycle. CONCLUSIONS: These data demonstrate that although the reproducibility of left atrial functional indices is poor, instantaneous left atrial cavity measurements with automatic boundary detection are reproducible. This suggests that automatic boundary detection may assist in serial non-invasive measurement of left atrial size to assess disease states and treatments.

Adult↗
PubMed1995

An audit of the accuracy of upper gastrointestinal diagnoses in Scottish Morbidity Record 1 data in Tayside.

INTRODUCTION: Scottish Morbidity Record (SMR1) data are coded by trained clerical staff from case records and discharge summaries. They form the basis of many strategic NHS decisions. Their accuracy for upper gastrointestinal (UGI) diagnosis is unknown and the study was undertaken to assess this accuracy in Tayside. METHOD: Patients who fulfilled the following criteria were identified using a record-linkage pharmacoepidemiological database, and their case records retrieved: over 50 years of age, had encashed at least one prescription for a non-steroidal anti-inflammatory drug at a Tayside pharmacy and who had SMR1 records containing one or more symptom/diagnosis codes between January 1989 and December 1991. Medically qualified staff were trained to examine case records and to code UGI diagnoses. They searched the case records for every UGI SMR1 entry for these patients from 1980-1992 and produced re-coded diagnoses (RCD) for each hospital event (admission and discharge), using all the data available in the case records. They also abstracted data on the clinical presentation, investigations and management of patients. Each event was then examined by a single medically qualified researcher who compared the original SMR1 codes with the RCDs. RESULTS: 2,101 patients had a total of 3,764 events in 1989-1991. 317 events were either day case procedures or elective surgery or the case records were not found. They were therefore excluded. Of the remainder, the SMR1 and RCD codes were judged equivalent in 1,608 events (46.6%). However, 1,005 SMR1 events (29.2%) contained a symptom code but no diagnosis code and the remaining 834 (24.2%) were judged suboptimal for other reasons. Of those with a symptom code only, 406 could not be improved upon and were transformed into RCD symptom codes only, 435 were assigned symptom and diagnostic RCDs and 164 were assigned diagnostic RCDs only. In the other 834 events, 279 had one or more diagnoses missing, 425 had one or more diagnoses inaccurate, 23 had both missing and inaccurate diagnoses and 107 were not UGI. Thus 1,433 (41.6%) of UGI SMR1 events could be more accurately coded. Examination of investigation data revealed that coding inaccuracy was not due to diagnostic procedures being carried out after admission. CONCLUSION: UGI SMR1 data were satisfactory in about half of all events. In about a quarter there were symptom codes but no satisfactory diagnosis codes, whilst in another quarter the data were inaccurate. These findings have implications for health care activities and research that use these data.

Aged↗
PubMed1995

Elevated blood pressure during the first two hours of ambulatory blood pressure monitoring: a study comparing consecutive twenty-four-hour monitoring periods.

OBJECTIVE AND DESIGN: Ambulatory blood pressure monitoring is being used increasingly in clinical practice and hypertension research. We have noted elevated blood pressure during the initial hours of monitoring. The objective of the present study was to examine the consistency, magnitude and duration of this elevation, and to determine whether this effect causes significant differences in the mean ambulatory blood pressure monitoring values comparing the first (day 1) and second (day 2) consecutive 24-h periods of monitoring. METHODS: Fifty patients who were hypertensive based on repeated clinic readings were studied prospectively. Each underwent continuous 48-h ambulatory blood pressure monitoring with a SpaceLabs 90207 monitor. The device recorded blood pressure at 15-min intervals during the daytime (0600-2159 h) and at 30-min intervals at night-time (2200-0559 h). From these readings hourly means were calculated. Repeated-measures analysis of variance was performed to compare the hourly means of days 1 and 2. RESULTS: Repeated-measures analysis of variance indicated that a significant difference existed for both systolic and diastolic blood pressure between day 1 and day 2. Paired Student's t-test revealed that this difference occurred during the first 2 h of monitoring. The daytime blood pressure was higher on day 1 as a result of the initial elevation of blood pressure at the onset of monitoring. The initial elevation of blood pressure was present both in white-coat hypertensives and in essential hypertensives. CONCLUSION: The first 2 h of ambulatory blood pressure monitoring are associated with elevated blood pressure both in white-coat hypertensives and in essential hypertensives. This has a minor effect on mean daytime and 24-h ambulatory blood pressures. We propose that improved ambulatory blood pressure monitoring recordings would be obtained in clinical practice, and more particularly in research applications, if 26-h ambulatory blood pressure monitoring was carried out, excluding the first 2 h from the summary analyses.

Adult↗
PubMed1995

Non-steroidal anti-inflammatory drugs and hospitalization for acute renal failure.

Non-steroidal anti-inflammatory drugs (NSAIDs) have been implicated in the aetiology of acute renal failure (ARF), but epidemiological studies examining this association have produced disparate results. We conducted a case-control study using a purpose-built record-linkage database for a population of 420,600 patients, resident in Tayside since May 1990. Patients (n = 207) hospitalized with a diagnostic code for ARF between 1990 and 1992 had their diagnosis validated by a renal physician. Six community controls and two hospital controls, matched for age and sex, were generated for each of these cases. Exposure to dispensed oral NSAIDs, topical NSAIDs and aspirin during the 90 days prior to the index date were investigated (recent exposure), as was exposure at any time since January 1989 (previous exposure). The most significant associations were modelled using conditional logistic regression. When community controls were used, recent exposure to NSAIDs and previous exposure to aspirin were independently associated with hospitalization for ARF, with adjusted odds ratios of 2.20 (1.49-3.25) and 2.19 (1.46-3.30), respectively. Only recent exposure to oral NSAIDs was associated when hospital controls were used: 1.84 (1.14-2.93). No significant interactions were present with previous chronic renal failure, other possible causes of ARF or whether the diagnosis was primary or secondary. There is an approximate doubling of the risk of hospitalization for ARF with use of oral NSAIDs.

Acute Kidney Injury↗
PubMed1995

A double-blind comparison of bisoprolol and atenolol in patients with essential hypertension.

We compared the beta 1-selective adrenoceptor antagonists bisoprolol and atenolol in a double-blind, randomized crossover study. After 4 weeks placebo phase, 59 patients with essential hypertension received either 10 mg bisoprolol or 50 mg atenolol once daily for 8 weeks, increased if necessary (target BP < or = 150/90 mmHg) to 20 and 100 mg, respectively, after 4 weeks. After a second placebo phase, crossover occurred to the alternative drug. We measured resting systolic and diastolic blood pressures and heart rate at 24 h post-dose baseline and after 4 and 8 weeks treatment. Both drugs significantly lowered systolic and diastolic blood pressures and heart rate at 8 weeks compared to baseline (all p < 0.05). Bisoprolol reduced heart rate significantly more than atenolol (p < 0.01), but systolic and diastolic blood pressure changes were not different between the two drugs. There was no difference in patient acceptability of the drugs as assessed by visual analogue scale. Despite theoretical and circumstantial evidence to suggest superiority of bisoprolol over atenolol, no significant difference between the two was found except for greater heart rate reduction with bisoprolol.

Atenolol↗
PubMed1995

QT dispersion in essential hypertension.

Increased QT dispersion is associated with sudden cardiac death in congestive heart failure, hypertrophic cardiomyopathy, and following acute myocardial infarction. Patients with hypertension, in particular those with left ventricular hypertrophy, are also at greater risk of sudden cardiac death. We examined whether QT dispersion, which is easily obtained from a routine ECG, correlates with echo LVH. Sixty-nine untreated patients with essential hypertension had QT dispersion measured from a surface 12-lead electrocardiogram, and two-dimensional echocardiography performed to measure interventricular septal thickness, posterior wall thickness, and left ventricular internal diameter. Office blood pressure was recorded, and in 56 patients, 24 h ambulatory blood pressure monitoring was also done. Multivariate analysis demonstrated significant relationships between QT dispersion and office systolic blood pressure, and left ventricular mass index. Similar findings were obtained when QT dispersion was corrected for heart rate (QTc dispersion). After patients with electrocardiographic left ventricular hypertrophy (n = 5) were excluded from the analysis, the above relationships persisted. Increased QT dispersion is thus found in those essential hypertensives at greatest risk of sudden death. Since this relationship persists even in the absence of electrocardiographic left ventricular hypertrophy, measurement of QT dispersion might be a simple, non-invasive screening procedure to identify those hypertensives at greatest risk of sudden death.

Adolescent↗