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Biomedical subjects

J A Hart

Publications and source records attributed to J A Hart.

18 recordsLinked to original sources
PubMed1985

The urethral catheter--a review of its implication in urinary-tract infection.

The research into acquisition of urinary-tract infection over the last few decades has established three ways in which organisms may gain access to the urinary tract of the catheterized patients: Firstly, during the process of passing the catheter into the bladder should complete asepsis not be observed; secondly by travelling along the urethra in the small, fluid-filled cavity between catheter and mucosa; Thirdly following contamination of the drainage system, along the inside of the catheter directly into the bladder. The relative importance of each route is not clear and is still the subject of much controversy but it would seem that all these routes have a part to play in allowing infection to develop. The risk of catheterized patients acquiring urinary-tract infection is so great that where possible catheterization should be avoided. The most important preventive measure which may be taken is to limit the duration of indwelling catheterization. In addition, a considerable amount of research has attempted to distinguish other factors which might affect the rate at which urinary-tract infection in the catheterized patient becomes established so that high-risk patients may be identified. The evidence indicates that the risk increases with duration of catheterization, age, length of hospital stay, immunosuppressant treatment, that it is greater in female than male patients and that a patient with a serious or fatal underlying disease is also more likely to develop bacteriuria. Finally, properties of the urine and the host defence mechanisms may affect the susceptibility of the individual to urinary-tract infection. Identification of the routes of infection and patients at risk is only part of the problem. The next stage is to formulate criteria for the care of catheterized patients which reduce the risk of infection to the absolute minimum and will hopefully go some way towards diminishing the unsatisfactory high levels of urinary-tract infection that are currently associated with indwelling catheterization.

Age Factors↗
PubMed1985

A study of the relationship between the pharmacokinetics and the pharmacodynamics of the 4-hydroxycoumarin anticoagulants warfarin, difenacoum and brodifacoum in the rabbit.

The pharmacokinetics and pharmacodynamics of the 4-hydroxycoumarin anticoagulants, brodifacoum, difenacoum, and warfarin have been studied in the rabbit. Sensitive (50 ng ml-1) and specific high performance liquid chromatography assays have been developed for the determination of plasma concentrations of warfarin, brodifacoum and difenacoum. After administration of a single intravenous dose (20 mumol kg-1), plasma concentrations of warfarin underwent mono-exponential decay, with a terminal half-life of 5.6 +/- 0.7 h (mean +/- s.e. mean), whereas plasma concentrations of brodifacoum and difenacoum underwent bi-exponential decay with terminal half-lives of 60.8 +/- 1.9 h and 83.1 +/- 10.3 h respectively. The plasma half-life of brodifacoum in a single patient poisoned with the compound was 487 h. The pharmacological response to the anticoagulants was measured as changes in prothrombin complex activity, from which the rate of clotting factor synthesis was determined. Clotting factor synthesis recovered in a monophasic fashion after a single intravenous dose of warfarin, compared with a more complex biphasic, pattern of recovery of clotting factor synthesis after administration of either brodifacoum or difenacoum. The slope (m) of the intensity of effect-log (amount of drug in the body) curve was derived for each anticoagulant. There was no significant difference in the value of m after single intravenous doses of racemic, R-, and S-warfarin, difenacoum and brodifacoum, which is consistent with the hypothesis that all the 4-hydroxycoumarin anticoagulants produce their anticoagulant effect by acting at the same receptor site, vitamin K epoxide reductase. Determination of the minimum plasma concentration of each anticoagulant that corresponded with the complete inhibition of clotting factor synthesis indicated that racemic warfarin, R-warfarin and brodifacoum have similar potencies in the rabbit and are less potent than S-warfarin and difenacoum.

4-Hydroxycoumarins↗
PubMed1984

A study of factors which determine the pharmacological response to vitamin K in coumarin anticoagulated rabbits.

The pharmacological response to vitamin K has been determined by measuring prothrombin complex activity (P.C.A.) in male New Zealand White rabbits anticoagulated (P.C.A. less than 20%) with the long acting 4-hydroxycoumarin brodifacoum, at a dose (10 mg/kg) which produces maximum antagonism of vitamin K1. Thus, according to current concepts, this animal model may be used to assess vitamin K requirements in the absence of a functional vitamin K-epoxide reductase. After intravenous administration of vitamin K1 (1 mg/kg) P.C.A. reached a maximum (64 +/- 19%) at 3 hr and then declined at a rate which corresponds to complete inhibition of clotting factor synthesis. Vitamin K2 (1 mg/kg) stimulated clotting factor synthesis for 2 hr, while cis-vitamin K1, vitamin K3, vitamin K1 2,3-epoxide and oral administration of vitamin K1 were ineffective. Plasma concentrations of vitamin K1 fell steeply during the 12 hr following administration of a pharmacological dose, and then declined with a terminal half-life of 18.9 +/- 9.0 hr. Comparison of the pharmacodynamic and pharmacokinetic data indicated that plasma concentrations in the range 0.4-1.0 microgram/ml are required for clotting factor synthesis in the limiting situation of maximum antagonism of vitamin K by coumarin anticoagulants. These findings explain why frequent and repeated administration of vitamin K1 may be necessary during coumarin poisoning.

Animals↗