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Biomedical subjects

N Hockings

Publications and source records attributed to N Hockings.

11 recordsLinked to original sources

Electrocardiographic prediction of coronary artery patency after thrombolytic treatment in acute myocardial infarction: use of the ST segment as a non-invasive marker.

The predictive value of the measurement of changes in ST segment elevation was assessed as a non-invasive marker of coronary artery reperfusion after thrombolytic treatment. Forty five patients with acute myocardial infarction (23 anterior, 22 inferior) of less than six hours' duration were given thrombolytic treatment by either the intravenous (n = 28) or the intracoronary route (n = 17). A proportional value for the shift in ST segment, termed the fractional change, was calculated both from 12 lead electrocardiograms and from the Holter tape for each patient. Coronary artery patency in an initial group of 22 patients (training group) was associated with a fractional change value of greater than or equal to 0.5 (100% specific, 88% sensitive by Holter analysis; 100% specific, 94% sensitive by 12 lead electrocardiogram). This rule performed well when it was applied to a test group of 17 patients (100% specific, 93% sensitive by Holter analysis; and 67% specific, 93% sensitive by 12 lead electrocardiogram). Linear discriminant analysis was then used to determine which features gave the best separation of those in whom there was reperfusion and those in whom there was not. This gave 100% specificity and 100% sensitivity when applied to the training group for either the 12 lead electrocardiogram or Holter monitoring. When it was applied to the test group, the sensitivity was maintained at 100%, but the specificity dropped to 33% irrespective of whether the basis of the test was Holter monitoring or the 12 lead electrocardiogram. These results suggest that a fractional change of >/= 0.5 calculated from a single lead showing myocardial injury is a useful non-invasive marker of reperfusion. The technique can be applied to either 12 lead electrocardiograms or Holter monitoring. The use of a more complex classification increased the sensitivity of the test at the expense of its specificity.

Adult↗

Thrombolytic therapy in acute myocardial infarction in the elderly.

Fifty-seven elderly patients (35 males, 22 females; age range 65-80 years, mean 70 years) with acute myocardial infarction received thrombolytic therapy within 8 h using either streptokinase or anisoylated plasminogen streptokinase activator complex. Coronary artery reperfusion was confirmed by early coronary arteriography. The overall reperfusion rate was 77%. Accurate non-invasive markers of reperfusion included: a rapid fall in the S-T segment elevation, an early peak of the creatinine phosphokinase enzyme curve and reperfusion arrhythmias. Clinical events suggesting early reocclusion occurred in 30%. Coronary arteriography was accompanied by local bleeding associated with the arterial puncture site in 2 patients and a cerebrovascular accident in 1 patient. Minor bleeding occurred in 6 other patients. In those where reperfusion occurred, the mortality at 1 month was 6.6% and in those who did not reperfuse or had early reocclusion 38%. At 1 year the figures were 10 and 46%, respectively.

Aged↗

Achievement of coronary artery patency by use of anisoylated plasminogen streptokinase activator complex in acute myocardial infarction.

Anisoylated plasminogen streptokinase activator complex (APSAC) is a recently developed thrombolytic agent with high fibrin-binding potential and sustained release pharmacokinetics (plasma half-life 70 minutes). Following studies of its intracoronary use, the efficacy was examined, in an open study using coronary angiography, of a single bolus dose of 30U given intravenously to 94 patients within 6 hours (mean 2.97 hours) from the onset of symptoms of myocardial infarction. After thrombolytic therapy, patency of the left anterior descending artery was demonstrated in 32 of 42 patients with anterior infarctions (76%), and in 12 of 13 patients with circumflex (92%) and 28 of 36 with right coronary artery infarcts (78%) in the inferior infarction group. The overall incidence of reocclusion was 24%, which occurred within the first 12 days after hospitalisation. Successful thrombolysis was associated with rapid resolution of the acute ST segment change, and an early peak of creatine phosphokinase (CK) compared with patients whose vessels remained occluded. No major systemic bleeding complications were experienced. Single dose intravenous APSAC appears to be a highly effective and relatively safe thrombolytic agent which has the major advantage over other such agents of easier administration. This makes it suitable for use in district hospitals and in the community, as well as in specialised cardiac centres.

Adult↗

The relationship between serum enalaprilat concentration and the hypotensive effect in man.

The relationship between serum concentrations of the angiotensin converting enzyme inhibitor, enalaprilat, and its antihypertensive action was investigated using integrated pharmacokinetic-dynamic modelling techniques. The model was parameterized in terms of slope "m", describing the sensitivity to the fall of blood pressure, and an intercept term "i". A linear pharmacodynamic model: E = m. ce(t) + i, adequately characterized the concentration-effect relationship in most of the young (aged 22-30 years) and elderly normotensive subjects (aged 65-73 years). However, no age-related differences were seen, indicating that angiotensin II vasoconstrictor action is unaltered by senescence.

Adult↗

The effects of age on carbamazepine pharmacokinetics and adverse effects.

The pharmacokinetics and effect of single oral doses of carbamazepine (400 mg) were compared in a group of six young volunteers aged between 20 and 25 years, and a second group of five elderly volunteers aged between 66 and 84 years. No age related changes in salivary or plasma pharmacokinetics or in psychomotor function were detected.

Adult↗

Age and the pharmacokinetics of angiotensin converting enzyme inhibitors enalapril and enalaprilat.

The pharmacokinetics of angiotension converting enzyme (ACE) inhibitors enalapril (10 mg orally) and its active metabolite, enalaprilat (10 mg intravenously) were studied in nine young healthy volunteers aged 22-30 years and nine sex matched elderly subjects aged 65-73 years. After both drugs, a biexponential curve was fitted to the decline in plasma enalaprilat concentration. Area under the plasma concentration-time curve (AUC) was greater in the elderly for both drugs. Clearance (CL) and clearance/bioavailability (CL/F) were less in the elderly for enalaprilat and enalapril, respectively. There was no difference in F between young (0.62 +/- 0.16) and elderly subjects (0.61 +/- 0.15). Enalaprilat CL and enalapril CL/F were significantly and positively correlated to endogenous creatinine clearance. There was a significant difference in the weight corrected volume of distribution at steady state after enalaprilat between the young and elderly (P less than 0.02). The relationship between plasma enalaprilat concentrations and percentage ACE inhibition, using the Hill equation, showed no difference in the sensitivity to ACE inhibition between the young and the elderly group. The pharmacokinetic differences observed are likely to be related to an age dependent decline in renal function as well as changes in body composition. Kinetic differences partly explain the greater pharmacodynamic response in the elderly.

Adult↗

Age and the pharmacodynamics of angiotensin converting enzyme inhibitors enalapril and enalaprilat.

The effect of age on the pharmacodynamic responses to converting enzyme inhibitors, enalapril and enalaprilat was investigated in nine young (22-30 years) and nine sex-matched elderly (65-73 years), healthy volunteers. The groups differed in baseline blood pressure, young 121/64 mmHg, elderly 142/75 mmHg (P less than 0.01), but not in sodium intake or body weight. Both enalapril and enalprilat produced significant falls in blood pressure in both groups but no increase in heart rate in the supine or erect posture. The blood pressure fall was significantly greater in the elderly on both treatments and in both erect and supine posture. The greater fall in blood pressure in the elderly was associated with a more prolonged inhibition of plasma angiotensin converting enzyme activity. The apparent age-related difference in response appears to be due to the difference in baseline blood pressures between the groups. Further study of the usefulness of chronic dosing with angiotensin converting enzyme inhibitors in hypertension in the elderly is indicated.

Adult↗

Lindau's disease and familial hyperparathyroidism.

A case of medullary hemangioblastoma is described occurring in association with familial hyperparathyroidism. The possibility that this combination may represent a previously unreported variant of Lindau's disease is discussed.

Brain Neoplasms↗

Factors affecting the response to inhibition of drug metabolism by cimetidine--dose response and sensitivity of elderly and induced subjects.

The effect of cimetidine on oxidative drug metabolism was characterised using antipyrine clearance in a group of healthy volunteers. In six subjects cimetidine produced a dose dependent reduction of antipyrine clearance: 400 mg/day (16.8 +/- 2.2%, mean +/- s.e. mean), 800 mg/day (26.3 +/- 1.5%) and 1600 mg/day (33.5 +/- 2.4%). The effect of cimetidine (800 mg/day) was of similar magnitude (approximately 25%) in two groups of six young (21-26 years) and six elderly (65-78 years) subjects. The effect of pretreatment begun just 1 h before administration of antipyrine was similar to that of 24 h pretreatment and that reported for chronic cimetidine pretreatment. The percentage reduction in antipyrine clearance produced by cimetidine 800 mg/day was greater (44 +/- 5 vs 24 +/- 3%; P less than 0.05) in six subjects who had been pretreated with the hepatic enzyme inducer rifampicin (600 mg/day for 21 days) than in the control uninduced state. Although cimetidine was capable of rapidly reversing the effect of rifampicin on antipyrine clearance, following withdrawal of both rifampicin and cimetidine there was still evidence of enzyme induction. These results suggest that the effect of cimetidine on oxidative metabolism is dose dependent, is more marked in enzyme induced subjects, is independent of the duration of pretreatment and is of similar magnitude in young and elderly subjects.

Adult↗

Alteration of pharmacokinetics after halving a slow-release theophylline tablet.

A study was carried out in 10 healthy volunteers to determine the effects on the bioavailability of theophylline from a biconvex-shaped, slow-release 400 mg theophylline tablet formulation when the tablet was taken whole or as two separate halves in a single dose. The subjects took one or other dosage regimen on different occasions separated by a 7-day washout period. The results showed that absorption was faster and plasma levels were higher when the 400 mg tablet was taken as 2 halves.

Adult↗