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Biomedical subjects

J S Walker

Publications and source records attributed to J S Walker.

At least 91 records · Page 5Linked to original sources
PubMed1984

The thermal death time curve for foot-and-mouth disease virus contained in primarily infected milk.

Whole and skim milk obtained from cows after intramammary and intravenous inoculation with foot-and-mouth disease virus (primarily infected milk) were exposed to various temperatures ranging from 80 to 148 degrees C for various times ranging from 2.5 s to 27 min then tested for viral infectivity. The average pretreatment titre of the 53 lots of milk used was 10(5.9) plaque-forming units of virus per millilitre 10(3.7)-10(6.8)). A thermal death time curve was plotted using the data obtained. The curve demonstrates that in order to inactivate the virus, times of over 20 min are necessary at 'low' temperatures (100 degrees C) while 2.5 s is sufficient at a temperature of 148 degrees C.

Animals↗
PubMed1984

Altered d-tubocurarine disposition during cardiopulmonary bypass surgery.

Kinetics of the neuromuscular blocker d-tubocurarine (dTc) were investigated in 13 adult patients undergoing surgery involving cardiopulmonary bypass (CPB). Approximately 1 hr before CPB surgery, each received dTc as an intravenous bolus of 0.6 mg/kg and a maintenance infusion of 3 micrograms/kg/min. dTc plasma concentration-time data before CPB did not differ from those reported in normal surgical patients. There was an abrupt discontinuity in the plasma concentration-time profile with the onset of CPB, and both total and free plasma concentrations increased 400% during the period of CPB. Although computer simulations suggest that these rises in dTc plasma concentrations can be attributed to contraction in central compartment volume, there also was decreased renal and total plasma clearance of dTc together with a prolonged elimination 1 1/2, which suggests that clearance processes of dTc are also altered as a result of CPB. A 27% rise in dTc free fraction in plasma during CPB could be attributed to hemodilution associated with the CPB procedure itself. Lower doses of dTc will need to be used in patients undergoing surgery that involves CPB unless the concentration-effect relationship for dTc is so altered that higher concentrations are needed to elicit the same response as in normal patients.

Adult↗
PubMed1983

Gallamine disposition in open-heart surgery involving cardiopulmonary bypass.

Kinetics of gallamine, a neuromuscular blocker, were investigated in 22 adult patients undergoing surgery involving cardiopulmonary bypass (CPB). Approximately 60 min before CPB, 11 patients received 480 mg gallamine IV; the other 11 patients received an initial dose of 240 mg IV, followed by another 240 mg through the pump priming fluid at the start of CPB. In 14 of our patients, the time course of gallamine concentrations in the plasma before, during, and after CPB was similar to that in normal surgical patients, indicating little or no effect of cardiac disease or CPB. In the remaining patients, perturbations were not observed before CPB, but with its onset there were varying changes, typically, rises in gallamine concentration ranging from an alteration during the period of CPB only or during the elimination phase, to an alteration at all times after starting CPB. Although the mechanism for this rise in gallamine plasma concentrations during and after CPB is not known, computer simulations suggest that it is due to a contraction in blood volume or decreased tissue perfusion during the period of extracorporeal circulation. Gallamine disposition differed only moderately in our patients from that in control patients. Therefore, from a kinetic viewpoint, provided that renal function is not impaired, gallamine is not contraindicated in CPB surgery.

Adult↗
PubMed1983

Alcuronium kinetics and plasma concentration-effect relationship.

The kinetics and dynamics of the neuromuscular blocker alcuronium were investigated in 12 surgical patients who received bolus and infusion regimens. In six patients the duration of the infusion was sufficiently long so that a steady-state alcuronium plasma concentration was reached (mean SD, 0.80 +/- 0.23 micrograms/ml). In the remaining six patients a steady state was not reached but the alcuronium concentration at the end of the infusion was 0.91 +/- 0.39 micrograms/ml. Alcuronium kinetic parameters did not differ between the two groups or from those obtained previously after bolus doses. In six patients for whom sufficient alcuronium concentration-time response data were available over the 0 to 100% response range, various mathematic models were used to characterize the concentration-effect relationship. A dynamic model incorporating a separate effect compartment connected to the central compartment was found to be the most appropriate. The (mean +/- SD) rate constant for equilibration of alcuronium concentration and effect was found to be 0.24 +/- 0.11 min-1, whereas the steady-state concentration required to induce 95% paralysis was 0.91 +/- 0.35 micrograms/ml (mean +/- SD).

Adolescent↗
PubMed1983

Alcuronium kinetics in patients undergoing cardiopulmonary bypass surgery.

1 The disposition of alcuronium was investigated in 10 patients undergoing surgery involving cardiopulmonary bypass (CPB) and compared with results from a group of non-cardiac patients studied previously. 2 After intravenous administration of a combined bolus and infusion dosage regimen, plasma concentrations fell in a bi-exponential fashion to a mean value of 0.55 micrograms/ml immediately before the start of extracorporeal circulation. 3 During CPB an apparent steady-state of alcuronium was reached immediately after commencement of CPB, however plasma concentrations were some 50% higher than those noted prior to commencement of CPB and those predicted using previous pharmacokinetic data from normal surgical patients. 4 Once CPB was completed and the alcuronium infusion terminated, post-infusion alcuronium plasma concentrations again appeared to decline bi-exponentially with time. 5 Of the pharmacokinetic parameters which were calculated model-independently, the apparent volume of distribution (Vss) was unchanged (329 vs 313 ml/kg) and the elimination half-life (t1/2,z) (532 vs 199 min) was prolonged and the plasma clearance (CL) (0.8 vs 1.34 ml min-1kg-1) markedly reduced in these patients compared to non-cardiac surgical patients. 6 As a result of these changes in alcuronium concentration during CPB and the diminished elimination of alcuronium following CPB, a closer monitoring of neuromuscular function may be necessary in cardiac patients undergoing CPB.

Adult↗
PubMed1983

Pharmacokinetic studies of 5-fluorouracil and 5'-deoxy-5-fluorouridine in rats.

The pharmacokinetics of 5-fluorouracil (FU) and its metabolic prodrug, 5'-deoxy-5-fluorouridine (dFUR), were investigated in 5- to 9-month-old rats without tumors. Intravenous bolus injections and infusions of FU (25-35 mg X kg-1) and dFUR (500-750 mg X kg-1) had activity against transplanted colon tumors in 2- to 4-month-old rats. Blood and plasma concentrations of FU and dFUR were analyzed by high-pressure liquid chromatography using 5-bromouracil as the internal standard. Free fractions of these drugs in plasma were indistinguishable from unity, indicating little or no protein binding. The area under the blood concentration-time profiles and the steady-state concentrations of unchanged dFUR were 40- to 100-fold higher than those of unchanged FU. The respective blood clearances of FU and dFUR were 44 and 18 ml X kg-1 X min-1 after i.v. bolus injections, which were significantly lower than the 108 and 26 ml X kg-1 X min-1 after infusion. FU clearance decreased when its infusion rate was increased from 25 to 50 mg X kg-1 X day-1. Renal clearances of both drugs remained the same after either route of administration. These data suggest that both drugs were eliminated by nonlinear kinetics and that their metabolism was saturated at a more rapid administration rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Determinants of d-tubocurarine plasma protein binding in health and disease.

d-Tubocurarine protein binding was determined in plasma from normal surgical patients; patients with renal dysfunction; patients with alcoholic cirrhosis; and patients scheduled for coronary artery surgery and was compared with binding determined in solutions of isolated human serum albumin (HSA). The free fraction of d-tubocurarine was independent of plasma drug concentration throughout the range 0.1-3.0 micrograms/ml. The free fraction of d-tubocurarine in renal disease (0.44 +/- 0.05), liver disease (0.53 +/- 0.05), and cardiac disease (0.49 +/- 0.05) was not significantly different from that in normal patients (0.50 +/- 0.04). Furthermore, the free fraction of d-tubocurarine was unrelated to plasma concentrations of total protein, total globulin, albumin, total lipids, or alpha 1-acid glycoprotein in the four patient groups. The free fraction of d-tubocurarine (0.55 +/- 0.02, n = 7) in solutions of HSA (0.58 mM) was similar to that observed in plasma. Albumin, therefore, appears to be the major plasma binding protein for d-tubocurarine.

Adolescent↗
PubMed1982

Cost of anaesthesia.

The major contributory factor to the cost of anesthesia today are the increases in medical salaries that have kept pace with inflation, commanding 68% of the total expenditure. The current position has been compared with that of 20 years ago. This outline could be used as a framework for departmental budgeting.

Anesthesia↗
PubMed1981

Dose-response curves for four neuromuscular blockers using continuous i.v. infusion.

Cumulative dose-response curves were constructed in man for tubocurarine, pancuronium, gallamine and alcuronium from data obtained during barbiturate-narcotic-nitrous oxide anaesthesia. Fifty-six adult patients received one of these drugs, administered by constant-rate infusion, a technique enabling response levels and results pooled to derive a composite dose-response curve for each drug. Using the mechanical twitch response, the ED50 for each neuromuscular blocking drug was: tubocurarine 0.236 mg kg-1, pancuronium 0.048 mg kg-1, gallamine 1.3 mg kg-1 and alcuronium 0.161 mg kg-1. The slopes of the composite curves for pancuronium and alcuronium were significantly steeper than those for tubocurarine and gallamine. In the alcuronium studies the simultaneous compound electromyogram was recorded, and usually this was more depressed than the mechanical twitch response, giving an ED50 of 0.135 mg kg-1.

Action Potentials↗