A dissertation submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of Masters of Science in Medicine (Pharmacology) Johannesburg, 2013 / Colon cancer is the third most common cancer worldwide and the second most common in the western world. More than 40 % of colon cancer sufferers develop metastases and chemotherapy is often used alone or in combination with radiotherapy as adjunctive therapy for the advanced disease. A major effort has been made in the past decade to develop anticancer agents through both empiric screening and rational design of new compounds. These attempts are made to improve the survival rate, reduce the severe adverse effects associated with existing cancer chemotherapeutic agents as well as to reduce the development of drug resistance. In the present study, two colon cancer cell lines were exposed to novel imidazo[1,2-a]pyridines and novel nucleoside analogues, aiming to investigate the cytotoxic efficacy on the cells, the mode of cell death, and to explore the pathways by which cell death was induced.

A research report submitted to the Faculty of Medicine, University of the Witwatersrand Medical School, in partial fulfilment of the requirements for the Degree Masters of Medicine in the branch of Psychiatry, Johannesburg, August, 2015 / Introduction Pharmacotherapy is a key component in the management of bipolar disorder. Whilst one might aim for fewer agents, not all patients with bipolar disorder can be stabilized with monotherapy and combination treatment (polypharmacy) is increasingly used to manage patients in clinical practice. Mood stabilizers have traditionally been prescribed as monotherapy, however the use of atypical antipsychotic agents is seen in clinical practice with various such agents approved for such usage. Combination treatment with an antipsychotic, preferably an atypical antipsychotic together with a standard mood stabilizer is also noted in clinical practice as well as recommended by guidelines. Bipolar patients managed in a specialist psychiatric setting have a greater chance of being managed with polypharmacy than in a general practice setting. The use of polypharmacy may also be attributed to receiving treatment in an academic environment. This current study was based on the application of diagnostic criteria and principles of the Diagnostic and Statistical Manual of Mental Disorders version IV TR (DSM IV TR), published by the American Psychiatric Association and The International Classification of Diseases version 10 (ICD 10), published by the World Health Organisation. Aims The study aims to describe the range and frequency of medications used in the management of bipolar bisorder in a specific setting as well as describe the nature and frequency of monotherapy versus polypharmacy use. Hypothesis The study hypothesized that the majority of patients attending the specialist / academic psychiatric outpatient clinic at Tara Hospital would be prescribed polypharmacy and that antipsychotics (typical or atypical) would be prescribed in combination with standard mood stabilizers in the majority of cases. Method The study took the form of a retrospective patient file review. The clinical files were for patients attending the Tara Hospital psychiatric outpatient clinic. The files of every patient who attended the clinic at least once in 2009 were screened and included in the study where the recorded ICD 10 code corresponded with a bipolar disorder subtype or a single manic or hypomanic episode. Where the recording of the ICD 10 code was missing or incomplete further scrutiny of the clinical notes enabled the researcher to establish a diagnosis of bipolar disorder using the ICD 10 and/ or DSM IV TR diagnostic criteria and therefore include the patient file in the study. Other necessary information was obtained by reviewing clinical notes as well as the prescription written on the last patient visit for 2009. Results The study found that the majority of patients (93.8%) were prescribed polypharmacy, with 3.2 the mean number of psychotropic medications prescribed per patient. Lithium was prescribed in 34.3% of patients. Sodium valproate was prescribed in 37.1% of patients. Eighty three point eight percent (83.8%) of the patients were prescribed at least one standard mood stabilizer. The atypical antipsychotics (46.6%) were prescribed more frequently than the typical antipsychotics (16.5%). Lamotrigine (31.8%) was the preferred novel anticonvulsant and the selective serotonin reuptake inhibitors (SSRI’s) were the most commonly prescribed antidepressant (28.9%). Clonazepam (26.8%) was the most frequently prescribed benzodiazepine add-on. The use of combination treatment to manage bipolar disorder was the rule rather than the exception. There was however much variety in the combinations used with no particular combination being prescribed in the majority of patients. Forty seven percent (47%) of the combinations used included a standard mood stabilizer and a typical or atypical antipsychotic. Conclusion The current study provides preliminary data on the prescribing patterns in bipolar disorder in a specialist psychiatric clinic within an academic complex in South Africa. The findings are in keeping with international studies and highlights that polypharmacy and combination treatment in the management of bipolar disorder is the norm in such settings. There is a large variation in clinician practices and much variety seen in the combinations of medications used to treat bipolar disorder despite the availability and use of treatment guidelines. This is perhaps because bipolar disorder is such a complex disorder and that most of the treatment recommendations are based on limited data. Treatment guidelines have emerged in order to attempt to standardize treatment and provide clinicians with algorithms to utilize and apply research findings in daily clinical practice. Further study into the effective prescribing principles for bipolar disorder is necessary.

by Yiu-chung Wong. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1991. / Bibliography: leaves 171-184. / Acknowledgements --- p.i / Abstract --- p.iii / List of Figures --- p.1 / List of Tables --- p.4 / Chapter Chapter 1 - --- General Introduction --- p.6 / Chapter Chapter 2 - --- A Gas-liquid Chromatographic Method for Studying the Effect of Adrenaline on Venous Plasma Concentrations of Bupivaca- ine after Interpleural Administration --- p.41 / Chapter Chapter 3 - --- Gas-liquid Chromatographic Determination and Physicoche- mical Studies of Six Clinical Used Local Anaesthetics --- p.64 / Chapter Chapter 4 - --- Improved Gas-liquid Chromatographic Method for the Quant- itation of Plasma Pethidine and Norpethidine --- p.88 / Chapter Chapter 5 - --- Determination of Pethidine and Its Major metabolites in Hu- man Urine by Cas-liquid Chromatography --- p.112 / Chapter Chapter 6 - --- Plasma Protein Binding Characterization of Pethidine and norpethidine --- p.131 / Chapter Chapter 7 - --- "A Comparative Study of Plasma Pethidine and Norpethidine in Caucasian, Chinese and Nepalese Patients after Intramus- cular Post-operative Pethidine" --- p.153 / Chapter Chapter 8 - --- Future Prospects of the Work --- p.168 / References --- p.171 / Appendices

by Say Tung Kun. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1998. / Includes bibliographical references (leaves 80-92). / Abstract also in Chinese. / Title --- p.i / Table of Contents --- p.ii / List of tables --- p.vi / List of abbreviations --- p.viii / Acknowledgements --- p.xi / Abstract --- p.xii / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Lipids: their nature and function in man --- p.1 / Chapter 1.2 --- Lipid metabolism --- p.2 / Chapter 1.3 --- The definition and classification of hyperlipidaemia --- p.3 / Chapter 1.3.1 --- The definition of hyperlipidaemia --- p.3 / Chapter 1.3.2 --- Lipid levels and diet in Hong Kong and other Chinese populations --- p.5 / Chapter 1.3.3 --- The classification of hyperlipidaemia --- p.8 / Chapter 1.3.4 --- The primary hyperlipidaemias: Genetic disorders of lipid metabolism --- p.8 / Chapter 1.3.5 --- The secondary causes of hyperlipidaemia --- p.8 / Chapter 1.4 --- The signs and symptoms of hyperlipidaemia --- p.10 / Chapter 1.4.1 --- The signs of hyperlipidaemia --- p.10 / Chapter 1.4.1.1 --- Corneal arcus --- p.10 / Chapter 1.4.1.2 --- Xanthomata --- p.11 / Chapter 1.4.1.3 --- Xanthelasmata --- p.11 / Chapter 1.4.2 --- The symptoms of hyperlipidaemia --- p.12 / Chapter 1.5 --- The investigations and monitoring of hyperlipidaemia during studies of drug treatment --- p.12 / Chapter 1.5.1 --- The clinical investigation of hyperlipidaemia --- p.12 / Chapter 1.5.2 --- The clinical and laboratory monitoring of hyperlipidaemia --- p.13 / Chapter 1.5.2.1 --- The clinical monitoring of hyperlipidaemia --- p.13 / Chapter 1.5.2.2 --- The laboratory monitoring of hyerlipidaemia --- p.13 / Chapter 1.6 --- The therapy of hyperlipidaemia --- p.13 / Chapter 1.6.1 --- The response to lipid-lowering drug therapy --- p.14 / Chapter 1.6.1.1 --- The response to the flbric acid derivatives --- p.15 / Chapter 1.6.2 --- Detection of hyperlipidaemia and benefits of treatment --- p.19 / Chapter 1.6.3 --- The significance of the present studies --- p.21 / Chapter Chapter 2 --- Hyperlipidaemia: relationship to other diseases --- p.23 / Chapter 2.1 --- Atherosclerosis --- p.23 / Chapter 2.2 --- Vascular Insufficiency Diseases --- p.24 / Chapter 2.3 --- Hypertension --- p.25 / Chapter 2.4 --- Diabetes mellitus --- p.26 / Chapter 2.5 --- Thyroid disorders --- p.30 / Chapter 2.6 --- Liver disease --- p.31 / Chapter 2.7 --- Pancreatitis --- p.32 / Chapter 2.8 --- Renal disease --- p.32 / Chapter 2.8.1 --- Nephrotic syndrome --- p.32 / Chapter 2.8.2 --- Chronic renal failure --- p.33 / Chapter 2.8.3 --- Renal transplant patients --- p.33 / Chapter Chapter 3 --- Patients and methods in the lipid studies --- p.34 / Chapter 3.1 --- Characteristics of patients with hypertriglyceridaemia in Hong Kong --- p.34 / Chapter 3.2 --- Clinical and laboratory methods to measure the response to drug treatment --- p.37 / Chapter 3.2.1 --- Clinical methods to assess the response to drug treatment --- p.37 / Chapter 3.2.1.1 --- History --- p.37 / Chapter 3.2.1.2 --- Physical examination --- p.38 / Chapter 3.2.1.3 --- Clinical measurement --- p.39 / Chapter 3.3 --- The laboratory methods to measure the lipid response to drug treatment --- p.39 / Chapter 3.2.1 --- The methodology for the extended lipid profile --- p.40 / Chapter 3.3.2 --- Statistical analysis --- p.41 / Chapter Chapter 4 --- Gemfibrozil dose-response study --- p.43 / Chapter 4.1 --- Dose-response study of gemfibrozil in Chinese patients with combined hyperlipidaemia --- p.43 / Chapter 4.1.1 --- Introduction --- p.43 / Chapter 4.1.2 --- Patients --- p.44 / Chapter 4.1.3 --- Results --- p.45 / Chapter 4.1.4 --- Discussion --- p.51 / Chapter Chapter 5 --- Gemfibrozil 900 mg tablet study --- p.53 / Chapter 5.1 --- Assessment of the efficacy and tolerability of a new formulation of gemfibrozil as a 900 mg tablet in the treatment of hyperlipidaemia --- p.53 / Chapter 5.2 --- Patients recruited --- p.53 / Chapter 5.3 --- Methods --- p.54 / Chapter 5.4 --- Results --- p.54 / Chapter 5.4.1 --- Tolerability --- p.54 / Chapter 5.4.2 --- Efficacy --- p.55 / Chapter 5.5 --- Discussion --- p.61 / Chapter Chapter 6 --- Bezafibrate study --- p.64 / Chapter 6.1 --- Assessment of the efficacy and tolerability of bezafibrate in the treatment of hyperlipidaemia --- p.64 / Chapter 6.2 --- Introduction --- p.64 / Chapter 6.3 --- Patients --- p.65 / Chapter 6.4 --- Results of bezafibrate study --- p.66 / Chapter 6.4.1. --- Tolerability --- p.66 / Chapter 6.4.2. --- Efficacy --- p.66 / Chapter 6.5. --- Discussion --- p.73 / Chapter Chapter 7 --- Discussion and Conclusions --- p.75 / Chapter 7.1 --- "Introduction: the two study drugs, gemfibrozil and bezafibrate" --- p.75 / Chapter 7.2 --- Gemfibrozil --- p.76 / Chapter 7.3 --- Bezafibrate --- p.77 / Chapter 7.4 --- Conclusion --- p.78 / References --- p.80 / Appendix I. Abstracts relating to these studies from presentations at national and international meetings --- p.93 / Appendix II. Side effect questionnaire used in the studies --- p.95

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 9 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 7 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 6 uppsatser.

No description available.

Aim: To determine whether the addition of nebulised ipratropium to the therapy of acute asthma leads to a cost-effective reduction in the mean duration of admission and time to maximum peak expiratory flow rate (PEFR). Method: Patients with an admission diagnosis of acute asthma were studied in a double-blind, placebo-controlled trial in which they received a standard therapeutic regimen of continuous intravenous aminophylline, 4-hourly fenoterol nebulisation, intravenous methylprednisolone 125mg 12-hourly, and, every four hours, either nebulised saline placebo or ipratropium bromide 500mcg in 3ml saline. Data on age, gender, initial and maximum PEFR, time to maximum PEFR, and duration of hospital stay was collected from the hospital record after discharge. Statistical techniques: 2-way contingency tables for categorical variables, 1-way ANOVA for treatment effects, and life-table analysis of the time till discharge. Results: Records of 279 of the 400 patients entered in the study were suitable for analysis after excluding re-admissions, non-asthmatics and incomplete records. Baseline comparisons of age and severity on presentation showed no significant differences. The trial group did not differ significantly from the control group with respect to either time to PEFR (respectively 21.11 hours (SD 14.3) versus 22.89 (SD 15.82)) or duration of admission (5.02 (SD 3.65) versus 5.38 (SD 3.13) 6-hour units). In a sub-group of patients (n=155) demonstrating more than 100% improvement in PEFR, the time to maximum PEFR was significantly shorter in the ipratropium group (20.35 hours SD 12.4) versus 25.20 hours (SD 17.0); p= 0.045). Conclusion: The addition of ipratropium bromide to a standard treatment regimen for acute asthma reduced the time to achieve maximum PEFR in a sub-group of patients with markedly reversible airflow limitation. Overall, however, the addition did not prove cost-effective.

Carbamazepine is a drug which is now widely used for the treatment of both generalised epilepsy (tonic-clonic seizures) and partial epilepsy (with simple or complex symptomatology). This study was undertaken in an attempt to assess the role of the metabolites of carbamazepine, viz. 10, 11-epoxy-carbamazepine and 10, 11-dihydro-10,11-dihydroxy-carbamazepine, with regard to their therapeutic efficacy and the occurrence of side effects of the parent drug. It was also designed to seek a possible explanation as to why certain patients with optimal levels of carbamazepine in plasma fail to respond to therapy. A total of 23 epileptic patients (11 females and 12 males) suffering from either generalised (tonic-clonic) seizures or partial complex seizures took part in the study. The patients were divided into two groups according to their seizure frequency: Responders - those patients who had no seizures in the month prior to entry into the study (12 patients). Non-Responders - those patients who had a minimum of one seizure a week in the month prior to entry into the study (11 patients). Carbamazepine and its metabolites were monitored between 8 a.m. and 6 p.m. by taking blood samples at two hourly intervals. Cerebrospinal fluid (CSF) was also obtained from seven patients in the non-responder group. The drug and its metabolites were assayed simultaneously by the thin-layer chromatographic (TLC) method of Hundt and Clark (1975). Six of the 23 epileptic patients complained of side effects: nausea and headaches were the most frequently mentioned complaint. Statistical analysis showed, however, that there was no significant difference in the peak levels of carbamazepine and metabolites in patients both with or without side effects. Therefore, it was not possible to define a threshold level of the drug above which side effects were likely to occur. Also, no definite conclusion could be reached as to whether the metabolites play a role in the manifestation of side effects. The area under the curve (AUC) is a measure of the overall plasma concentration of carbamazepine and metabolites (present between 8 a.m. and 6 p.m.) in the individual patients of the two groups. There was no significant difference in the AUC of carbamazepine between responders and non-responders. However, the AUC of the dihydroxy and epoxy metabolites was significantly higher in the non-responders (P<-0.002 and P < 0.02 respectively). Moreover, in the CSF samples of the non-responders, the mean (±SD) ratio of the dihydroxy metabolite to the parent drug was as high as 1.17 (±0,36). The results show a clear association between high levels of metabolites and poor response to carbamazepine therapy. Furthermore, it would seem that either both metabolites are inactive or that if the epoxy metabolite is active as in the rat (Frigerio and Morselli 1975), any likely therapeutic effect is counter-acted by the relatively large concentration of inactive dihydroxy metabolite (Schmutz et al 1979). Moreover, it may follow that non-response to carbamazepine - despite optimal levels of the drug in plasma - may be due to competition by inactive dihydroxy metabolite for the site (s) of action of the parent drug in the brain. Research strategies which might be used to test this hypothesis have been proposed.