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C A Duggan

Publications and source records attributed to C A Duggan.

7 recordsLinked to original sources

Changing prescribing in the light of tolerability concerns: how is this best achieved?

Despite our knowledge regarding the efficacy, tolerability and optimal use of drugs, suboptimal prescribing still occurs. In view of all the factors that influence prescribing, this is not surprising. The focus of drug tolerability has changed from 'choosing the best alternative' when a drug is prescribed, to a balanced decision incorporating various different treatments from separate healthcare providers. This article reviews strategies that may influence prescribing behaviour and discusses practical considerations for achieving optimal prescribing in view of tolerability concerns. The patient has a major influence on prescribing and, with the current diversification of healthcare, the patient now controls prescribing behaviour more than ever before. Communication between healthcare providers consequently assumes a vital role. If messages are to be coherent and transferable, it is increasingly important that healthcare workers communicate effectively with one another regarding patients, prescribing patterns, and drug tolerability issues.

Drug Prescriptions↗

Reduction of embryonic intracellular pH: a potential mechanism of acetazolamide-induced limb malformations.

The effects of acetazolamide on the developing rodent limb bud were postulated to result from a reduction of intracellular pH (pHi). Embryonic intracellular pH was calculated from transplacental distribution of the weak acid, 5,5'-dimethyloxazolidine-2,4-dione, in teratogenically sensitive (C57BL/6) and resistant (SWV) inbred mice. pHi was reduced by acetazolamide treatment in C57 embryos and limb buds but not in SWV samples. Acetazolamide teratogenesis can be exacerbated by coadministration of amiloride, presumably through inhibition of Na+/H+ exchange attributable to the latter agent. pHi reduction after such treatment was more profound than after acetazolamide alone, providing further support for the central hypothesis. pH was also reduced in other embryonic (embryo plasma) and extraembryonic compartments (exocoelomic fluid, amniotic fluid). pH changes in these compartments could also lead or contribute to abnormal development.

Abnormalities, Drug-Induced↗

Decreasing pH of rat embryos and fluids estimated by transplacental distribution of DMO.

Utilizing the transplacental distribution of a weak acid, 5,5-dimethyloxazolidine-2,4-dione (DMO), we have measured the pH of cells within the rat embryo in vivo on days 11.5-14 of gestation. This is a period of rapid organogenesis in this species when the cells of many organ systems begin to change from a proliferative mode into a differentiated state. We found that intracellular pH of the day 11.5 rat embryo is 7.47 +/- 0.03 and decreases steadily to day 14 at which time it reaches 7.11 +/- 0.03. Because there is a concomitant fall in proliferative rate over this span of development, we suggest this correlation to be additional evidence of an association between proliferation and alkalinization of the cell interior. A number of other compartments including embryo plasma, amniotic fluid, exocoelomic fluid, and yolk sac have a decreasing concentration of DMO as development advances, indicative of a steadily declining pH. These changes could have developmental and pharmacokinetic implications.

Animals↗

One-minute electrochemical enzymic assay for cholesterol in biological materials.

In this rapid and specific micro-scale electrochemical enzymic assay for cholesterol and cholesterol esters, 10 microL of standard or sample is injected directly into a heated (50 degrees C) thermostated, oxystated cuvet containing pH 7.25 buffer, cholesterol oxidase (EC 1.1.3.6), and cholesterol esterase (EC 3.1.1.13). The cholesterol esters are hydrolyzed by the esterase, and the cholesterol is simultaneously oxidized by the oxidase. The hydrogen peroxide produced from oxidation of the unesterified cholesterol is measured by a polarographic anode covered with an acetate/polycarbonate membrane. The membrane allows hydrogen peroxide to diffuse to the platinum anode, where it is oxidized, but prevents the diffusion of ascorbic acid, uric acid, and bilirubin to the electroactive surface. Turbidity does not interfere. The correlation (r) between results by our method and the Abell-Kendall method for 105 samples of serum was 0.9994 and for 105 samples of plasma was 0.9997. Our method is convenient for the analysis of high-density lipoprotein cholesterol in plasma and serum supernates and in many kinds of tissue homogenates. Its limitations are also described.

Cholesterol↗

Implanted electroenzymatic glucose sensors.

The advent of electrochemical sensors for intermittent sampling of blood gases and hydrogen ions in the clinic, intensive care, and surgical units has revolutionized diagnostic and critical care medical technics. The use of electrochemical sensors for continuous transcutaneous monitoring of blood gases is further enhancing the medical surveillance of patients. The more recent introduction of glucose and other electroenzymatic sensors has stimulated broad research in the development of metabolic monitoring. For the present research, the glucose sensor widely used for the rapid specific micro-analysis of whole blood and plasma is explored for possible use as an in vivo intravascular or tissue-implanted sensor. This sensor is based on the polarographic measurement of hydrogen peroxide generated by glucose oxidase (EC 1.1.3.4) held between two membranes. The first membrane allows the diffusion of glucose, ions, and many other small molecules, while the second membrane allows the diffusion of the glucose-generated hydrogen peroxide to the platinum surface, but excludes ascorbic acid, bilirubin, and uric acid. Such sensors respond rapidly and specifically when acutely implanted subcutaneously in cats and dogs. They function well as glucose-sensor-tipped venous catheters. One sensor was repeatedly used for in vitro polarograms, subcutaneous and blood glucose monitoring, over a period of ten months, with storage in the cold between uses, with the complete retention of its response characteristics.

Animals↗