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Biomedical subjects

T M MacDonald

Publications and source records attributed to T M MacDonald.

At least 163 records · Page 9Linked to original sources
PubMed1990

An evaluation of the A&D UA-751 semi-automated cuff-oscillometric sphygmomanometer.

We compared blood pressure recordings made with the A&D UA-751 semi-automated cuff-oscillometric sphygmomanometer (A&D Co. Ltd, Tokyo, Japan) and with a conventional Hawksley random-zero mercury sphygmomanometer (Hawksley and Sons Ltd, Lancing, UK). Simultaneous single-arm recordings were obtained in duplicate with both devices in 200 subjects having blood pressure in the ranges 92-221/51-121 mmHg. The measurements obtained by three observers using the Hawksley sphygmomanometer were compared with recordings from two A&D UA-751 devices. In most cases, there was an acceptable level of agreement between the results, according to the criteria suggested by the Association for the Advancement of Medical Instrumentation (range of differences systolic: mean - 0.9 to 1.4 mmHg, s.d. 4.6-9.8 mmHg; diastolic: mean - 0.6 to 1.3 mmHg, s.d. 2.9-5.1 mmHg), although there were sizeable discrepancies in individual subjects. Thus the A&D UA-751 device appears to be an acceptable alternative to a conventional sphygmomanometer; it should be suitable for routine clinical and limited research use, including intermittent home blood pressure recording.

Blood Pressure Determination↗
PubMed1990

Bench and ambulatory field evaluation of the A & D TM-2420 automated sphygmomanometer.

Adequate evaluation of automated sphygmomanometers, in terms of safety, accuracy, mechanical reliability, patient acceptability and ability to record ambulatory blood pressure is essential before these devices are used in clinical practice and in clinical trials. We have evaluated the accuracy and performance of the A & D TM-2420 automated sphygmomanometer, an auscultatory device designed for ambulatory blood pressure recording. Four devices were tested for accuracy by simultaneous comparison against two experienced observers using standard mercury column sphygmomanometers. Two of these devices developed faults that precluded complete evaluation. One of the remaining devices met and one failed to meet the somewhat liberal criteria for accuracy recommended by the American Association for the Advancement of Medical Instrumentation, the current standard for evaluation (mean difference of less than or equal to 5 mmHg and standard deviation of differences less than or equal to 8 mmHg). The mean differences (standard deviation of differences) between observers for simultaneous triplicate observations of systolic/diastolic pressure in 50 subjects, including 35 hypertensives, were 0.8 (3.0)/-0.6 (2.4) mmHg. In comparison, the differences between each device and each observer were: device 11, observer 1, -6.4 (5.4)/-6.3 (9.9); device 11, observer 2, -5.6 (4.7)/-7.0 (10.4); device 12, observer 1, -4.9 (5.2)/-4.0 (7.5); device 12, observer 2, -4.1 (4.9)/- -4.5 (7.7) mmHg. Ambulatory trials were carried out with a further 10 devices. Of these, seven developed faults requiring their return to the supplier. Numerous additional problems were encountered with microphones, cuffs, leads and connections, the processing unit, error algorithms and data-handling software. The device was not capable of making truly ambulatory recordings. We do not confirm the previously favourable, but limited, evaluation of this device. We stress the vital importance of subjecting a number of devices to benchtesting for accuracy, and the need to undertake extensive 'field' testing before any devices can be considered suitable for ambulatory recording. Exercise testing under laboratory conditions is not an adequate substitue for true ambulatory evaluation.

Algorithms↗
PubMed1990

The pharmacokinetics of gamma-glutamyl-L-dopa in normal and anephric rats and rats with glycerol-induced acute renal failure.

1. The pharmacokinetics of gamma-glutamyl-L-dopa (gludopa) and its metabolite, L-dopa, have been studied in normal rats at three dose levels of gludopa: 2 mg kg-1, 5 mg kg-1 and 7.5 mg kg-1. The extent of metabolism in normal rats, and the pharmacokinetics in anephric rats and rats with glycerol-induced acute renal failure (ARF) were also studied at a gludopa dose of 2 mg kg-1. 2. Gludopa was extensively metabolised to L-dopa with only about 10% of an injected dose being excreted unchanged. Normal rats had a rapid gludopa clearance of 50.9 +/- 9.6 ml min-1 kg-1 and elimination rate constant of 2.99 +/- 0.27 h-1. The mean residence time and half-life were 20.9 +/- 1.4 and 14.4 +/- 1.0 min, respectively. The apparent volume of distribution at steady state was 1.05 +/- 0.18 l kg-1. 3. No statistically significant differences were found in the main pharmacokinetic parameters between ARF and controls for either gludopa or its metabolite L-dopa. 4. In anephric rats and controls the kidneys were found to contribute about 68.5% and 67.2% to the elimination of gludopa and the metabolite L-dopa, respectively. 5. These results confirm that gludopa is an efficient pro-drug for L-dopa, and that the kidneys are the major site of gludopa metabolism. It seems likely that the renal specificity of gludopa persists in ARF.

Acute Kidney Injury↗
PubMed1989

The effect of carbidopa and lithium on the systemic and renal response to acute intravenous saline loading in normal man.

To assess a possible role for endogenous renal dopamine in sodium excretion, the dopa decarboxylase inhibitor carbidopa was given during intravenous salt loading. In addition, the effect of lithium on tubular sodium handling was separately determined. Nine males were studied randomly on three occasions, receiving placebo, lithium carbonate (1000 mg, 11 h prior to study) or carbidopa (100 mg x 2). On each day a baseline period was followed by infusion of isotonic saline (20 ml/kg per hour) over 3 h, and 6 h recovery. With placebo, sodium excretion increased markedly to a peak in the hour after infusion (0.15 +/- 0.03 to 0.73 +/- 0.12 mmol/min, P less than 0.01). Urine dopamine excretion increased modestly (1.33 +/- 0.12 to 1.67 +/- 0.13 mmol/min, P less than 0.01). Carbidopa effectively blocked dopamine output during the study. However, the natriuretic response was comparable to values on placebo at all time points. Fractional lithium clearance, a proposed measure of proximal tubular fluid rejection, increased significantly during saline infusion. However, baseline sodium excretion was greater in the presence of lithium, and plasma renin activity (PRA) was significantly elevated. In addition, the peak natriuretic response was smaller and cumulative sodium excretion reduced by 40% (P less than 0.01) compared to placebo. This study provides no evidence for a facilitatory role for dopamine in the natriuretic response to intravenous salt loading. Lithium, at subtherapeutic levels, cannot be presumed to be an inert marker, and clearance data must be interpreted with caution.

Adult↗
PubMed1989

The renal and haemodynamic effects of a 10 h infusion of glutamyl-L-dopa in normal man.

1. gamma-L-glutamyl-L-dopa (gludopa) and placebo were given by intravenous infusion to 12 healthy salt replete men for 10 h in a single-blind randomised fashion. 2. Gludopa caused a cumulative natriuresis of 46.5 mmol compared with placebo with a biphasic pattern and this was associated with a small reduction in body weight. 3. A small fall in arterial blood pressure and rise in pulse rate was seen with gludopa. 4. Plasma renin activity, atrial natriuretic peptide and urine kallikrein excretion were unchanged by gludopa but a small fall in urine aldosterone excretion, urine flow rate and free water clearance occurred. 5. The renal effects of gludopa are modest and last for only a few hours after the start of infusion.

Adult↗
PubMed1989

Frusemide, ACE inhibition, renal dopamine and prostaglandins: acute interactions in normal man.

1. The acute effects of intravenous frusemide (30 mg) on prostaglandin dependent renal haemodynamics, urinary prostaglandin excretion, urinary dopamine excretion and electrolyte excretion were studied in six salt replete healthy volunteers with and without pretreatment with the angiotensin converting enzyme (ACE) inhibitor, ramipril (5 mg) and compared with the effects of ramipril alone in order to clarify the role of the renin-angiotensin system in these responses. 2. Frusemide increased natriuresis (UNaV), kaliuresis (UKV), inulin clearance and plasma renin activity (PRA) and ramipril pretreatment significantly enhanced these effects suggesting that the acute generation of angiotensin II (AII) may attenuate these actions of intravenous frusemide. 3. Frusemide increased para-aminohippurate (PAH) clearance, osmolar clearance and urine flow but did not change filtration fraction or urinary kallikrein excretion. Pretreatment with ramipril did not affect these responses. 4. Frusemide increased the excretion of urinary PGE2 and 6-keto-PGF1 alpha. Ramipril pretreatment did not suppress this rise in prostaglandin excretion. Since the frusemide induced prostaglandin dependent renal haemodynamic changes were also not suppressed with ACE inhibition, this suggests that in salt-replete volunteers AII does not significantly modulate renal prostaglandin production after frusemide. 5. Urinary free dopamine excretion increased with frusemide alone. With ramipril pretreatment this rise showed a tendency to increase. AII may therefore inhibit the rise in urinary dopamine excretion after frusemide. However this requires further study.

Adult↗
PubMed1989

The renal effects of atrial natriuretic peptide in man are not attenuated by (+)-sulpiride.

1. Human alpha atrial natriuretic peptide (ANP) was infused intravenously for 1 h in eight healthy salt-replete men on two occasions, with and without pretreatment with (+)-sulpiride. 2. ANP increased sodium excretion and urine flow rate but did not alter blood pressure or plasma renin activity. 3. (+)-sulpiride had no significant effect on baseline creatinine clearance, sodium excretion or urine flow rate and did not alter the increases in these parameters with ANP. 4. It is unlikely that the renal effects of ANP are mediated by dopamine DA1-receptors in man.

Adult↗
PubMed1989

Blood pressure, renin-angiotensin-aldosterone axis and cortisol changes during withdrawal from alcohol.

Nineteen patients who had been drinking on the day of admission had significantly raised levels of renin, aldosterone and cortisol and a non-significant increase in angiotensin II. Five patients were hypertensive (systolic blood pressure greater than 160 mmHg or diastolic blood pressure greater than 95 mmHg) at some point during the study and there was a significant tachycardia. Over the first 4 days of abstinence there were falls in all of the measures reaching significance for renin, cortisol, systolic blood pressure and pulse. There were no correlations between blood pressure and any of the hormones measured although there was a significant association between pulse and both aldosterone and cortisol. It is concluded that the activity in the renin-angiotensin axis and hypothalamic-pituitary-adrenal axis is not responsible for alcohol-related changes in blood pressure.

Adult↗
PubMed1988

A comparison of the renal actions of gamma-L-glutamyl-L-dopa and gamma-L-glutamyl-L-tyrosine in normal man.

1. The renal responses to the dipeptides gamma-L-glutamyl-L-dopa (gludopa) and gamma-L-glutamyl-L-tyrosine (glutyrosine) were compared when given intravenously in six normal male volunteers. 2. Gludopa is natriuretic and diuretic at a dose of 25 micrograms min-1 kg-1. At the same dose, glutyrosine had no effect on the volume or sodium content of the urine. 3. There was a 400-600-fold increase in urine dopamine output after gludopa; there was no conversion of glutyrosine to dopamine. 4. Gludopa significantly inhibited plasma renin activity, whereas with glutyrosine there was a non-significant increase. 5. Gludopa is a potent pro-drug for renal dopamine production and exerts natriuretic and hormonal effects. Glutyrosine appears to be inactive. The results support the contention that circulating L-dopa is the important physiological precursor for renal dopamine.

Adult↗
PubMed1988

The effect of carbidopa and indomethacin on the renal response to gamma-L-glutamyl-L-dopa in normal man.

1. The renal response to gamma-L-glutamyl-L-dopa (gludopa, 25 micrograms kg-1 min-1) was investigated in seven normal male volunteers. The effects of oral carbidopa (100 mg) and indomethacin (100 mg) on the response to gludopa were studied in the same group. 2. Gludopa at this dose level produced a 900-fold increase in urine dopamine excretion and caused a natriuresis and suppression of plasma renin activity with only minor effects on pulse rate and blood pressure. 3. Carbidopa inhibited the increase in dopamine excretion by 97% and abolished the renal actions of gludopa. 4. The increase in urine dopamine produced by gludopa was not altered by indomethacin and the urine sodium output was similar to that caused by gludopa alone. 5. Gludopa is an effective renal dopamine prodrug whose activity can be blocked by the dopa decarboxylase inhibitor carbidopa. The results with indomethacin suggest that dopamine and the prostaglandins form separate natriuretic systems in the kidney.

Adult↗
PubMed1988

(+)-sulpiride antagonises the renal effects of gamma-L-glutamyl-L-dopa in man.

1. gamma-L-glutamyl-L-dopa (gludopa) was given by intravenous infusion to six healthy salt-replete men on two occasions, with and without pretreatment with (+)-sulpiride. 2. Gludopa increased sodium excretion, glomerular filtration rate and effective renal plasma flow whilst decreasing plasma renin activity. 3. (+)-sulpiride had no significant effect on baseline natriuresis, renal haemodynamics or plasma renin activity, but significantly attenuated the rise in sodium excretion, glomerular filtration rate and effective renal plasma flow produced by gludopa. 4. (+)-sulpiride abolished the acute fall in plasma renin activity seen with gludopa. 5. (+)-sulpiride raised serum prolactin concentration but did not affect the ris in urine dopamine excretion rate caused by gludopa. 6. Gludopa exerts its renal effects by stimulating specific dopamine receptors which are principally of the DA1 subtype.

Adult↗
PubMedDate not supplied

The multiple propensity score for analysis of dose-response relationships in drug safety studies.

In order to detect adverse drug reactions, large observational drug safety studies are necessary as randomized clinical trials rarely have enough power. However, in order to obtain reliable results the issue of confounding, especially confounding by indication, should be addressed. We proposed a multiple propensity score, which is an extension of the propensity score, to reduce the bias in a dose-response analysis in a drug safety study. The multiple propensity score has similar properties to the propensity score in Rosenbaum and Rubin.(1) Using the propensity score for bias reduction of the risk ratio was considered. We used the multiple propensity score in a study of the dose-response relationship between diclofenac prescriptions and hospitalization for gastrointestinal bleeding and perforation using a record linkage database. We found that the unadjusted risk ratios were biased downwards due to confounders and that this bias was reduced by using stratification based on the multiple propensity score.

Adult↗
PubMedDate not supplied

A pharmacoeconomic comparison of misoprostol/diclofenac with diclofenac.

OBJECTIVES: To estimate the economic impact of misoprostol/diclofenac in a fixed combination tablet compared with diclofenac. DESIGN: Cohort study with a prospectively constructed, population-based, record-linkage database containing details of exposure to all community dispensed NSAIDs and all admissions to hospital for upper gastrointestinal (GI) diagnoses. Costs associated with each study drug exposure were analysed using generalized linear models. SETTING: The population of Tayside, Scotland. SUBJECTS: Subjects aged 20 years and over who received misoprostol/diclofenac or any other NSAID between January 1989 and 31 December 1995. MAIN OUTCOME MEASURES: Total costs for the number of days of exposure to diclofenac and misoprostol/diclofenac, plus costs of concomitant ulcer healing drug therapy plus endoscopy procedures plus costs of admissions to hospital for upper GI diagnoses. RESULTS: The rate of hospitalization with gastrointestinal events was 30% higher among patients receiving diclofenac than that for patients receiving misoprostol/diclofenac. Among patients who received diclofenac and an ulcer-healing drug (UHD), the event rate was more than twice that for patients receiving misoprostol/diclofenac. In patients with a prior GI history, switching from diclofenac to misoprostol/diclofenac would reduce the costs of hospitalization. The resulting savings would more than offset the extra prescription costs. In patients without a prior GI history, the greatest potential saving would arise due to reduced use of UHDs and net savings would occur in subjects aged between 60 and 70 years of age or more. CONCLUSION: Use of misoprostol/diclofenac instead of diclofenac can produce cost savings due to reduced hospitalization rates and decreased use of UHDs in subjects with a prior history of GI disease and in older subjects without prior GI disease. These findings have implications for the management of patients who require treatment with NSAIDs.

Adult↗
PubMedDate not supplied

Nonadherence with ACE inhibitors is common and can be detected in clinical practice by routine serum ACE activity.

Our objective was to assess whether serum angiotensin-converting enzyme (ACE) activity during routine clinical practice accurately reflects patient adherence to ACE inhibitor treatment in chronic heart failure (CHF). During 1994-95, ACE was measured in 73 CHF patients who were routinely attending the heart failure clinic at Ninewells Hospital. At the same time, the Medicines Monitoring Unit collected data on whether and when prescriptions for ACE inhibitors were redeemed at community pharmacies, which enabled each patient's adherence over a prolonged period to be assessed. We then correlated whether an elevation in serum ACE was associated with poor adherence with ACE inhibitor treatment. In total, 18% of CHF patients appeared to exhibit less than 70% adherence with their ACE inhibitor treatment, with 34% exhibiting less than 85%adherence and 58% exhibiting less than 100% adherence. A serum ACE activity of more than 12 U/L gave 91% positive predictive accuracy that the patient was less than 100% adherent with his or her ACE inhibitor treatment. At the other extreme, a serum ACE less than 6.5 U/L gave 81% positive predictive accuracy that the patient was more than 85% adherent with ACE inhibitor treatment. Nonadherence with ACE inhibitor treatment, therefore, was found to be common in patients with CHF. The simple, inexpensive test of serum ACE activity can be used in CHF patients to identify many, although not all, nonadherent patients so that adherence-enhancing strategies can be targeted toward them. Further work is clearly required to explore the precise clinical utility of this promising test. (c)2001 by CHF, Inc.

Journal Article↗
PubMedDate not supplied

Evaluating the use of a semiautomated cuff-oscillometric sphygmomanometer in the hypertension clinic.

Measuring blood pressure in the clinic setting is confounded by 'white coat' hypertension, observer bias and digit preference. In this study a semiautomatic blood pressure measuring device (the UA-751) was tested for its use as a reliable assessment of blood pressure and improved patient management in the hypertension clinic. Blood pressures were recorded in 156 patients and compared with physicians' readings measured using a standard mercury sphygmomanometer. The mean blood pressure differences between the two methods showed that the device gave consistently higher readings for both systolic (1.4-3.6 mmHg) and diastolic (3.6-3.8 mmHg) pressure, whether it was used before or after physician consultation. No reduction in 'white coat' hypertension was thus apparent. There was considerable variability between recordings made by the two methods on the same individual. Digit preference was apparent with physician readings, with zero recorded in 57.8% of systolic readings compared with 12.2% using the machine. Different management decisions would have been taken in 20 (13.6%) patients had the UA-751 recordings been used. The device is thus of no value in patient management in the setting of the hypertension clinic.

Blood Pressure Determination↗