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Biomedical subjects

A H Thomson

Publications and source records attributed to A H Thomson.

72 records · Page 4Linked to original sources
PubMed1987

Changes in lignocaine disposition during long-term infusion in patients with acute ventricular arrhythmias.

Lignocaine disposition was studied in 30 patients with acute ventricular arrhythmias. Serum concentrations of lignocaine, its metabolites Monoethylglycine xylidide (MEGX) and glycine xylidide (GX), and alpha 1-acid glycoprotein (AAG) were analyzed during and after a 48-h lignocaine infusion. AAG concentrations tended to rise in patients with acute myocardial infarction (AMI), leading to binding of the drug in plasma. Lignocaine clearance was estimated at various times during the infusion using a Bayesian parameter estimation program and was found to decline over the course of the infusion. There was a significant reduction in clearance based on estimates obtained at the end of the infusion compared with estimates obtained during the first 0-5 h. Clearance was reduced both in patients who had an AMI and those who did not. Multiple linear regression analysis of the clearance data revealed that these changes could be described by a linear function of time and AAG concentration. These findings suggest that other factors in addition to protein binding changes may influence lignocaine disposition during long-term infusion.

Acute Disease↗
PubMed1987

Nocturnal cough in asthma.

The timing of nocturnal cough and its association with change in ambient temperature was documented in 11 asthmatic children, median age 5.1 years, while they were receiving continuous prophylaxis. Studies were performed in their homes on three nights. A voice activated system with electronic time signal recorded coughing. Ambient temperature was recorded every five minutes throughout the night on a Grant Squirrel data logger. Ten children coughed on 27 nights with a median of six bouts of coughing a night (range 0-272). The cough rate in the two hours after going to bed was significantly higher than the cough rate in the middle of the night (2-4 am or 4-6 am). Peak coughing times were 7-9 pm and 6-8 am. The room temperature was lowest between 5 and 7 am. There were no significant differences between cough rates during periods of rapid temperature change (more than 1 degree C an hour). The timing of nocturnal cough observed in this study differed from the known basophase of circadian cycles described for adults and children.

Asthma↗
PubMed1987

Population pharmacokinetics of lisinopril in hypertensive patients.

If optimal dosage administration schedules are to be defined, the factors that influence the disposition of a drug in the population of patients who are likely to receive it should first be determined. Traditionally, separate groups of patients, each with different underlying disease, are given the drug and then detailed studies are performed to assess which groups have significantly different pharmacokinetic parameters and therefore require an adjustment in dose. An alternative approach, utilizing large groups of patients studied less intensively, will be described here. The analysis used the results of two multicenter trials of lisinopril: one in elderly (greater than 65 years) hypertensive patients and one in a group of hypertensive patients with impaired renal function (creatinine clearance rate less than 60 ml/min). Both protocols allowed for a stepwise increase in the dose of lisinopril until optimum control of BP was achieved. Required dosages ranged from 2.5 to 40 mg/day. During the course of therapy, regular trough concentrations were analyzed to assess compliance and a steady-state profile was determined during one dosage interval. Only patients who appeared to be compliant on the basis of multiple trough concentrations were used in the analysis. Data from a total of 53 patients were used, of whom 35 took part in the elderly study, and 18 in the renal study. There were 25 men and 28 women in this combined study group with ages ranging from 21 to 85 years (mean 65 years) and weights from 51 to 115 kg (mean 72 kg).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Disopyramide in acute myocardial infarction: problems with changing pharmacokinetics.

In the acute phase of myocardial infarction it is recognized that serum disopyramide concentrations may be lower than expected. This has generally been attributed to reduced oral bioavailability. This report describes data obtained routinely from 6 patients with acute myocardial infarction and cardiac dysrhythmias treated initially with intravenous disopyramide. Serum disopyramide concentrations were consistently lower than expected, on average by 2.6 micrograms/ml. This was interpreted as being due to relatively high drug clearance, calculated as 6.7 +/- 1.5 l/h, compared to expected values of 3-4 l/h. Dosage schedules determined on the basis of the acute phase pharmacokinetics subsequently produced higher than predicted concentrations at later times on average by 2.8 micrograms/ml. Clearance at this time was calculated to be 3.1 +/- 0.6 l/h. Thus even with intravenous disopyramide therapy there are problems with changing pharmacokinetic parameters after myocardial infarction.

Aged↗
PubMed1986

The pharmacokinetics of R- and S-tocainide in patients with acute ventricular arrhythmias.

The pharmacokinetics of R(-) and S(+)- tocainide were studied in twelve patients requiring intravenous tocainide. In all patients, a progressive increase in the S(+):R(-) ratio was observed during the infusion. Mean +/- s.d. ratios increased from 1.03 +/- 0.05 at 2 min to 1.76 +/- 0.35 at 48.5 h. Data from eight patients were fitted to a two-compartment model and there was a significant difference (Wilcoxon matched-pairs test P less than 0.01) in the clearance estimates for the two enantiomers. The median values were: S(+)-tocainide = 6.25 l h-1 and R(-)-tocainide = 9.31 l h-1. There was no differences in V1 or Vss.

Acute Disease↗
PubMed1985

Evaluation of nonlinear regression with extended least squares: simulation study.

A new approach to nonlinear least-squares regression analysis using extended least squares (ELS) was compared with three conventional methods: ordinary least squares (OLS); weighted least squares 1/C (WLS-1) and weighted least squares 1/C2 (WLS-2). With Monte Carlo simulation techniques, 3 X 200 data sets were constructed with constant proportional error (5, 10, and 15% error) and 3 X 200 with constant additive error (0.05, 0.10, and 0.15 g/mL) from an initial (perfect) data set based on known parameters. Two sampling strategies were employed: one with 17 time points and one with 10 time points. All data sets were fitted by each of the four methods, and parameter estimation bias was assessed by comparing the mean parameter estimate with the known value. The relative precision of each method was investigated by examination of the absolute deviations of each individual parameter estimate from the known value. ELS performed as well as the appropriate weighting scheme (WLS-2 for constant proportional error sets and OLS for constant additive error sets) and was superior with regard to both bias and precision to less appropriate methods.

Kinetics↗
PubMed1985

Gastro-oesophageal reflux and childhood asthma: the acid test.

The presence of gastro-oesophageal reflux was investigated in 18 children with moderate to severe asthma by overnight oesophageal pH monitoring. Appreciable reflux was found during sleep in eight; its relevance to nocturnal asthma was not clear. On another occasion the same children were challenged in a double blind fashion with a drink of dilute hydrochloric acid (0.001 N) and the response of the airways was monitored by peak flow measurements and by histamine challenge tests. There was a significant increase in mean histamine sensitivity (p = 0.001) 90 minutes after the acid drink without any associated change in baseline peak flow rate. Eight children had a significant response to the acid drink, and a further three reacted to a more concentrated solution (0.01 N). In those asthmatic children in whom reflux is associated with a positive response to an acid drink (five out of 18 in the present study) it seems likely that reflux exacerbates nocturnal symptoms.

Adolescent↗
PubMed1984

Clinical pharmacokinetics: a comprehensive system for therapeutic drug monitoring and prescribing.

Clinical pharmacokinetics is an expanding scientific discipline which can make an impact on treatment in coronary care, intensive care, paediatrics, general medicine and surgery, and general practice. The aim of this study was to establish a rapid system of drug assay, to report the result, to assess the influence of pathological and clinical factors on the pharmacokinetics of certain drugs, and to use a computer to determine the optimum dosage of drugs. The clinical pharmacokinetics laboratory in Stobhill is available to all clinical departments and to general practitioners in the area. Digoxin, theophylline, and phenytoin have been assessed. Initial samples of these drugs showed that only about a third were in the therapeutic range; samples obtained after the issue of the laboratory report showed an improvement. The predictive performance of the computer program improved with feedback of one or two drug concentrations. Dosages of drugs chosen on an empirical basis may not lead to optimum treatment, and by testing samples early the dosage of the drug can be adjusted. It is hoped that the results achieved will encourage other clinical, pharmaceutical, and scientific colleagues to develop laboratories along similar lines.

Digoxin↗
PubMed1984

Estimation of gentamicin clearance and volume of distribution in neonates and young children.

Gentamicin therapy should be guided by serum level monitoring in all age groups, dosage adjustments depending on age related changes in pharmacokinetics. Population data analysed from two centres (43 infants from Glasgow and 100 infants and children from Manchester) by the computer program NONMEM showed that volume of distribution was related to body weight by a proportionality factor that decreased from the region of 0.41-0.46 l/kg in children less than 3 months to 0.25-0.32 l/kg in older children, a value which merges with that accepted for adults (0.25 l/kg). In both young and older children, clearance was also found to be dependent on body weight. Renal function (creatinine concentrations) provided no further explanatory power. When these results were used prospectively to forecast gentamicin concentrations with a Bayesian kinetic parameter estimation program, trough concentrations were more precisely predicted than peaks when a single concentration measurement was used. In clinical practice, however, two concentration measurements are usually routinely available and these should lead to greater precision of both peak and trough predictions. These results have been incorporated into a simple nomogram which can be used to determine a dose of gentamicin which will achieve target peak concentrations in infants, assuming that troughs should not exceed 2 micrograms/ml.

Age Factors↗
PubMedDate not supplied

Noninvasive ventilation for the management of pulmonary hypertension associated with congenital heart disease in children.

The use of noninvasive ventilation to support children with secondary pulmonary hypertension has not previously been reported. We present four children with secondary pulmonary hypertension in association with complex congenital and acquired cardiorespiratory anomalies who have been successfully managed in hospital and then discharged into the community on noninvasive ventilation, thus placing them in environments more suited for growth and development.

Child, Preschool↗
PubMedDate not supplied

Maximum voluntary cough: an indication of airway function.

Maximum voluntary coughing produces a flow-volume profile which incorporates the characteristics of a maximum expiratory flow-volume curve (MEFV). The cough flow-volume curve also has transient spikes of supramaximal flow, interspersed with portions of zero flow when the glottis is closed. The peak flow rates of the supramaximal flow transients during cough decrease in a linear fashion as lung volume goes down from total lung capacity to residual volume. Cough flow-volume curves have been recorded from forty-two subjects between the ages of 7 and 56 yr. The rate of change of cough peak flow shows a positive correlation with airway conductance measured plethysmographically in children. The ratio of forced expiratory flow to cough peak flow (the cough ratio) expresses the maximum expiratory flow rate during forced expiration as a proportion of that which can be achieved with a cough. The cough ratio declines during adult life, because although there is a fall in cough peak flow with age there is a proportionally greater fall in MEFV-equivalent flow. These investigations explore the information to be gained from cough flow-volume curves by examining the cough in a heterogeneous group of individuals.

Adolescent↗
PubMedDate not supplied

The total compliance of the respiratory system during the first year of life.

Respiratory system compliance (Crs) was measured in 34 spontaneously breathing infants during the first year of life. An occlusion technique was used whereby several expiratory occlusions were performed at different lung volumes within the tidal range. The airway opening pressure generated during a plateau after occlusion was related to the volume included above the end-tidal level by a regression equation. The slope of this equation represented the compliance of the infant's respiratory system; the intercept was significantly different for preterm (-0.5 ml) and post-term (-5.5 ml) infants and may represent the difference between end-expiratory lung volume during tidal breathing and the relaxed functional residual capacity. The values for respiratory system compliance were similar to those previously reported for infants during muscle relaxation. As a function of body length, Crs = 1.58 X length3.13 X 10(-4) ml . kPa-1. The technique described is simple to apply and is independent of oesophageal pressure measurements.

Body Height↗