Thesis (M.S.)--University of Michigan, 1983.

Thesis (M.S.)--University of Wisconsin--Madison, 1982. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 83-86).

Thesis (M.S.)--University of Michigan, 1987.

Thesis (M.S.)--University of Michigan, 1987.

Thesis (M.S.)--University of Michigan, 1983.

This study was designed to describe the use of analgesics ordered pro re nata (PRN) in the management of acute post-operative pain. Specifically, the study purpose was to answer the following questions. What amounts and frequencies of analgesic are ordered PRN by physicians for patients in the first 48 hours following a cholecystectomy? What amounts and frequencies of analgesic are given by nurses to patients in the first 48 hours following a cholecystectomy? What is the patient's summational description of his/her pain at 24 and 48 hours following a cholecystectomy? A descriptive survey design was used. A convenience sample of 22 subjects participated in the study. These subjects met the study criteria and were scheduled for elective cholecystectomy at one of the two hospitals used. Data were gathered by auditing the charts for information pertinent to the prescriptions and administration of the analgesics and by interviewing the subjects. There was considerable variability in the amounts and frequencies of analgesics prescribed and in those given to the post-operative subjects. No routine patterns were identified. There was a significant difference in the amounts of analgesics prescribed and given between the two hospitals, the reasons for which were not explored. The decision to use the PRN-prescribed analgesics appeared to be made by the nurses but evidence of accountability taken by nurses for their role in assessing pain and evaluating the effectiveness of the analgesics was not reflected in the reviewed records. Analgesics for use in the Post-Anaesthetic Recovery Room in the immediate post-operative period were prescribed by the anaesthetists. All initial analgesics were given by the intravenous route in this setting. Subjects at Hospital B were prescribed and received considerably more analgesics (83%) than those at Hospital A. Analgesics for use on the ward were prescribed by the surgeons. All orders were for meperidine hydrochloride to be given PRN and all orders were unchanged for the 48-hour period studied. The amount of meperidine prescribed and given per intramuscular dose was usually within the 75 to 100 milligrams optimal dosage range for the drug. The meperidine was usually prescribed with a four hour interval between doses. Doses of meperidine were given with considerably longer intervals between doses than the duration of action of the drug. For the 48-hour period, the mean total amount prescribed, based on the maximum possible dosage was 1154 milligrams. The median total amount prescribed was 1050 milligrams. The mean total amount given was 625 milligrams or 54% of the prescribed amount and the median total amount given was 587 milligrams or 56% of the prescribed amount. Subjects on the ward at Hospital A were prescribed and given significantly more meperidine than those at Hospital B. The patients' summational descriptions of their pain emphasized the individuality of the pain experience. The physical sensations described were consistent with previous literature descriptions of postoperative pain. The subjective data collected reflected the difficulties and complexities of pain management. An often-stated assumption in the literature is that nurses use PRN-prescribed analgesics inappropriately in managing post-operative pain; that is, patients are uncomfortable because the analgesics are not given in adequate amounts or frequently enough. In this study, a relationship was not identified between the amounts of meperidine received by subjects and how they reported their post-operative pain. This finding suggests that the assumption, that increasing the analgesics used would increase patient comfort, requires further investigation. Based on the findings of this study, implications for postoperative pain management and nursing practice, and suggestions for further research were made. / Applied Science, Faculty of / Nursing, School of / Graduate

The pharmacokinetics of phenytoin is complicated by the nonlinearity of the dose-concentration relationship which is a consequence of capacity-limited metabolism. Individualized therapy with phenytoin is therefore optimally required. As no data are available on the population pharmacokinetics of phenytoin in the Western Cape, this study was undertaken to address this issue. This study was conducted prospectively primarily to: (1) investigate the influence of various patient variables on the population pharmacokinetic parameters of phenytoin, (2) assess whether the parallel Michaelis-Menten and first-order elimination model provides a better fit to the data than the Michaelis-Menten model, (3) determine population pharmacokinetic parameter estimates of phenytoin representative of the patient population, and (4) validate and compare the clinical applicability of the parameter estimates and the models. The study population comprised 332 black and coloured, adult, male and female epileptic patients residing in the Western Cape, South Africa. All patients were on phenytoin monotherapy for the management of their epilepsy and no drugs known to interfere with phenytoin pharmacokinetics were taken concurrently. Clinical pharmacokinetic dosing services were initiated at 9 clinics from which patients were selected for this study. The service entailed a patient interview, a chart review, drug analysis and provision of either a written or verbal consultation report. The data were analyzed using NONMEM (nonlinear mixed-effects modelling), a computer programme designed for population pharmacokinetic analysis that allows pooling of data from many individuals. The Michaelis-Menten and the parallel Michaelis-Menten and first-order elimination models were fitted to 853 steady-state dose: serum concentration pairs.

Cis-platinum is a widely used cytotoxic agent with known radiosensitising properties. It is used in the treatment of various types of lung cancer that may include radiation to the lung as part of the treatment protocol. There is little evidence and some conflict as to whether it sensitises pulmonary tissue to the effects of radiation treatment. This project investigates the effect of cis-platinum alone or in combination with radiation on mouse lung. Four end points were used to evaluate treatments. They were: the release of pulmonary surfactant, changes in breathing rate, a histology based score of damage and changes in TGF-β - a cytokine important in the development of fibrosis. Single doses of either cis-platinum or radiation, cis-platinum given immediately before a single dose of radiation, cis-platinum given immediately before the first of two fractions of radiation and cis-platinum given at various times before and after a single dose of radiation were investigated. Cis-platinum alone was observed to cause an increase in the phospholipid content of lavaged surfactant. Cis-platinum was observed to cause an early release in surfactant and a trend existed for it to induce an early increase in breathing rates as compared to that induced by radiation alone. Cis-platinum was observed to increase radiation damage as assessed using a histology based scoring system. Higher TGF-β levels in lavaged surfactant were observed in C57 /Bl mice as compared to Balb/C. No difference in TGF-β levels was seen in homogenised lung between the strains. Cis-platinum may cause changes in TGF-β in C57/Bl mice but further work is necessary to confirm this.

The use of aminoglycosides in the treatment of the febrile neutropaenic patient with haematological disease is difficult and often suboptimal. This study reviews the available literature to establish therapeutic guidelines in this population and then reports the use of a Bayesian statistics based predictive model to implement and manage therapy in 10 patients. A review of the literature on aminoglycoside Pharmacology and clinical use is essential to determine therapeutic guidelines for this population. Aminoglycosides are amino sugars in glycosidic linkage and are polycations at physiological PH. The antibiotic effect is mediated through inhibition of protein synthesis and disruption of cell membrane integrity. Principal use is in treatment of Gram negative infection although aminoglycosides have activity against some Gram positive organisms including staphylococci. Aminoglycosides are inactive against anaerobes. Acquired resistance is mediated by bacterial enzymatic drug metabolism. Aminoglycosides are nephro- and ototoxic, this is the major constraint in clinical use.

A dissertation submitted to the Faculty of Medicine, University of the Witwatersrand, Johannesburg, in fulfilment of requirements for the degree of Medicine in Psychiatry. Johannesburg, March 1991. / In the first part of the dissertation a literature survey is done, looking at 1. An overview of dysthymic disorder. 2. An overview of serotonin and its involvement in psychiatric disorder [Abbreviated Abstract. Open document to view full version]