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Biomedical subjects

M J Jamieson

Publications and source records attributed to M J Jamieson.

11 recordsLinked to original sources

Determination of alpha-adrenergic blocking potency.

Determination of the alpha-adrenergic blocking potency of drugs in humans is usually done by measuring the shift in the blood pressure versus logarithm of intravenous phenylephrine dose-response relationship. Change in blood pressure activates homeostatic reflexes that may change this relationship. This study examines the effect of autonomic (beta 1- and beta 2-adrenergic, parasympathetic, and alpha-adrenergic) blockade on the dose versus blood pressure response relationship to sequential doses of phenylephrine in humans. Phenylephrine dose responses were conducted under controlled conditions, during propranolol and atropine infusion, during prazosin-induced alpha 1-adrenergic blockade, and during prazosin, propranolol, and atropine administration. Propranolol-atropine infusion decreased the threshold dose of phenylephrine required to increase mean blood pressure (p less than 0.00001), increased the slope of the phenylephrine dose versus increase in mean blood pressure relationship (p = 0.019), and and decreased the dose of phenylephrine required to increase mean blood pressure by 20 mm Hg (p less than 0.00001). Determination of the alpha-adrenergic blocking potency of prazosin was not affected by autonomic blockade with propranolol and atropine (dose ratio 5.2 before and 5.0 after autonomic blockade; p = 0.465). We conclude that beta 1- and beta 2-adrenergic and muscarinic blockade increase sensitivity to phenylephrine by increasing the slope and decreasing the threshold dose of the phenylephrine dose-response curve, and that alpha-adrenergic-blocking potency of prazosin may be determined with or without blocking homeostatic blood pressure regulatory mechanisms in humans.

Adrenergic beta-Antagonists

A comparison of the chronic effects of oral xamoterol and enalapril on blood pressure and renal function in mild to moderate heart failure.

1. We compared the effects, after 3 weeks oral therapy, of xamoterol 200 mg twice daily and enalapril 2.5, 5 or 10 mg twice daily on home and clinic blood pressure, glomerular filtration rate (GFR) and renal plasma flow, stroke and minute distances, linear resistance and on plasma renin activity in 19 patients with mild to moderate heart failure in a single-blind randomised crossover study. 2. Enalapril reduced mean home blood pressure by 17/7 mm Hg compared with xamoterol (P less than 0.0001) and by 19/7 mm Hg compared with placebo. Compared with placebo xamoterol had no effect. Enalapril reduced predose blood pressure, compared with xamoterol, on average by 15/5 mm Hg (P = 0.02 systolic, 0.09 diastolic) and by 20/7 mm Hg compared with placebo. At 4 h post-dose the mean differences were: xamoterol-enalapril 13/10 mm Hg (P = 0.01 systolic, 0.0007 diastolic) and placebo-enalapril 23/9 mm Hg. 3. Stroke and minute distances were marginally less 4 h following xamoterol than following enalapril: mean (s.e. mean) values were 9.4 (0.7) vs 10.4 (0.8) cm (P = 0.23) and 699 (51.7) vs 767 (62.1) cm (P = 0.04) respectively. Linear resistance was reduced by enalapril, from the placebo value of 13.2 (1.2) to 11.0 (0.9) mm Hg m-1 and marginally increased by xamoterol, to 14.2 (1.2) mm Hg m-1, the difference between active treatments being statistically significant (P = 0.03). 4. Renal plasma flow, GFR and filtration fraction were not influenced by enalapril or xamoterol therapy. There were no significant correlations between glomerular filtration rate and either blood pressure or stroke distance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists

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

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

The measurement of blood pressure: sitting or supine, once or twice?

In 166 patients attending a hypertension review clinic, we compared supine and sitting blood pressure measurements and first and second measurements (1 min apart) in each position to determine whether any differences seen might have implications for the routine measurement of blood pressure in these patients, as a group or as individuals. Measurements were made with the Copal UA-251 semi-automated sphygmomanometer. In the group there was no significant difference between the first and the second diastolic measurements. The first systolic measurement was on average 3-4 mmHg higher than the second in both positions. Mean supine systolic pressures were 2-3 mmHg higher and diastolic pressures 2-3 mmHg lower than the corresponding sitting pressures. In individual subjects there were substantial disagreements between successive measurements in both positions and between positions. However, these differences would not have influenced blood pressure management in more than a few instances. We suggest that two measurements should routinely be taken, and the average recorded, particularly when the average exceeds 155/90 mmHg.

Blood Pressure Determination

Effect of food on oral availability of apresoline and controlled release hydralazine in hypertensive patients.

Hydralazine is a vasodilator antihypertensive drug that has been in use for many years. Efficacy after oral administration correlates well with the levels of the drug in blood. Factors such as food ingestion that affect blood levels of hydralazine may therefore be of importance. There is dispute regarding the effect of food intake on blood levels of hydralazine and on the antihypertensive response. This randomized cross-over study examined the effect of food (642 K calories, 25 g protein, 43 g fat, 40 g carbohydrates, 32 mEq sodium, 17 mEq potassium) ingested immediately before hydralazine (taken as Apresoline, Ciba Geigy, or as slow-release hydralazine, SRH, Pennwalt Corporation) on the blood levels of hydralazine in 16 essential hypertensive patients who were slow acetylators currently taking at least 100 mg Apresoline daily. Peak blood hydralazine levels were reduced by food after both Apresoline and SRH, by 69 and 66%, respectively. Time to peak blood hydralazine concentration was delayed significantly with SRH. We could detect a statistically significant food-related reduction of area under blood hydralazine concentration versus time curves (AUC) only with Apresoline (by 44%). The AUC for SRH was decreased only 29% by food. Hydralazine should be taken at a consistent time with respect to meals.

Administration, Oral

Alpha adrenergic blocking activity of urapidil in man.

Urapidil is a new antihypertensive vasodilator agent whose pharmacologic action in man has not yet been fully defined. We have assessed the alpha adrenergic blocking activity of urapidil 15 and 30 mg given intravenously in a single blind study in 8 healthy volunteers. Urapidil produced dose-dependent parallel shift of the phenylephrine log dose/blood pressure response curve, consistent with significant competitive peripheral alpha 1 antagonism. Mean dose ratios were 2.99 and 5.48 for the 15 mg and 30 mg doses respectively. The pA2 for alpha 1 blockade is 7.3. Given these data, the major mechanism of antihypertensive effect of urapidil may be alpha 1 antagonism in the peripheral vasculature.

Adrenergic alpha-Antagonists

The analysis of dose-response curves--a practical approach.

The rationale for the objective assessment of dose-response curves (DRCs) is presented. Using data derived from isoprenaline/heart rate responses studies, two new statistical methods of objectively defining the terminal linear segment of an incomplete DRC are presented. Using data derived from phenylephrine/diastolic blood pressure response studies, the parallel shift quadratic model of Sumner et al. (1982) has been extended to include a measure of the suitability of the quadratic model for each individual data set using the Akaike information criterion. A parallel shift Emax model is proposed for complete DRCs.

Blood Pressure

The assessment of the beta-blocking activity of urapidil: a new method.

Urapidil is an antihypertensive vasodilator agent whose pharmacological action in man has not yet been fully defined. We have assessed the beta blocking activity of urapidil 15 mg and 30 mg i.v. in a single blind study of 10 healthy male volunteers. Urapidil at plasma concentrations in the same range as those shown to have antihypertensive affect did not significantly attenuate the chronotropic effect of isoproterenol. Propranolol 5 mg iv, the positive control, significantly shifted the isoproterenol dose-response curve to the right. We describe a new method of analyzing incomplete dose response curves whereby a linear terminal segment can be reproducibly defined.

Adrenergic beta-Antagonists

Hyponatraemia.

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Extracellular Space

Hypercalcaemia.

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Diagnosis, Differential