Background: The D-Dimer test has a high negative predictive value used primarily to exclude clinically suspected possible thrombo-embolic disease. In Emergency Unit (EU) practice, this test is often done not only for suspected Pulmonary Emboli (PE) but also to rule out atypical PE. In South Africa, diagnostic usefulness of this test has not been evaluated in a private hospital EU. The health profile of patients presenting in public and private EUs is different and therefore, it was hypothesized that the usefulness of the DDimer test in these two settings may be different. Results of this study may inform private hospital EU best practice in the optimal utilization of this test. Objective: To evaluate the usefulness of the D-Dimer test in the diagnosis of PE at the Morningside MediClinic (MMC) private hospital EU in Johannesburg, South Africa. Patients and Methods: After approval by the University of the Witwatersrand Human Research Ethics Committee, audit of clinical records was done at the MMC EU from 1 March to 1 June 2009. Informed consent was not required from study subjects as the study was done retrospectively with data extracted from clinical records in an anonymous and delinked fashion. The study population included all patients who had a D-Dimer test done in the MMC EU as part of their diagnostic workup. Extracted data included demographic information, diagnoses and confirmatory tests done. Continuous and categorical variables of data collected were summarized using Stastistica version 9.0 statistical package. A Wells Score was calculated according to the Wells Criteria. Results: In the study period, 189 of 2948 (5%) patients seen at MMC EU had D-Dimers measured. Their population mean age was 57 years (range 38 – 84 years) and 51% were males. Positive D-Dimers were present in 40 (21%) of the total patient population sample group (189 patients). Within the diagnostic categories, the following percentages were the results found per category of the positive D-Dimers within each category: PE (5)(100%), Chest Infection (5)(56%), AMI (2)(33%), Arrhythmia (2)(33%), Hypertension (2)(25%), Chest Pain (6)(14%), Anxiety (3)(23%), Headache (1)(14%), Syncope (1)(14%) and Others (13)(32%). The mean Wells Score in PE was 3.6 (3.0-4.5.) indicating medium probability of PE. All other diagnostic groups had low probability Wells Scores. It was impossible to comment on findings in public hospitals, as there is no known literature found to date on an audit performed concerning the usefulness of the D-Dimer test in a public hospital or any of the public sector, in Johannesburg or elsewhere in South Africa, regarding the diagnosis of PE. However, data has been published by other countries regarding the D-Dimer in various hospital and EU settings (public and private). Conclusion: In the cohort, the D-Dimer was done in only a fifth of patients seen at the private MMC EU and it was positive in less than half of cases. The test yield was highest in PE and had high negative predictive value in more than half of non-PE diagnoses. Therefore, the results suggested that a positive D-Dimer is highly predictive of a diagnosis of PE in this private EU. A negative D-Dimer result appears to be largely associated with any of the non PE wide differential of diagnoses.

Thesis (M. Phil.)--University of Hong Kong, 1985.

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

published_or_final_version / Biochemistry / Master / Master of Philosophy

Thesis (M.Med.Sc.)--University of Hong Kong, 2001. / Includes bibliographical references (leaves 100-109 (1st group)) Also available in print.

Nattokinase is a potent fibrinolytic enzyme produced by Bacillus sutbilis, which is one of the most important sources of fibrinolytic enzymes. Nattokinase has a dual function of hydrolyzing blood thrombin directly and indirectly. It was found to be active between pH 6-12 and lose fibrinolytic activity dramatically when pH is lower than 5. Currently nattokinase preparations are not pure enough to get rid of the unique smell that is repulsive to the non-Japanese. These two reasons severely blocked nattokinase to be developed for food and pharmaceutical industrial usages as supplements and active ingredients. The objective of this study was to isolate the bacteria which have ability to produce nattokinase-like fibrinolytic enzyme, purify and characterize these enzymes to determine the actual biochemical properties. An industrial compatible aqueous protocol can be applied not only for the purification of nattokinase but also for other fibrinolytic enzymes from Bacillus source was established to purify the enzymes to homogeneous. The intrinsic stabilizing factors in raw nattokinase fermented broth were also identified in order to make natural stable nattokinase preparation for acidic environment. 71 strains belonging to 13 different genus was determined as the fibrinolytic enzyme producing bacteria. The fibrinoytic enzyme produced by Bacillus tequilensis, Bacillus amyloliquefaciens, and Bacillus cereus was purified and characterized. One of these three enzymes was determined to be a new fibrinolytic enzyme that never be reported. The purification protocol established here contained 3 operation units that including one chromatographic separation step followed by membrane polishing after nattokinase was extracted with 70% ammonium sulphate from the fermented broth. The purified nattokinase and other fibrinolytic enzymes showed single band as tested by SDS-PAGE and already pure enough to determine the N-terminal sequence directly by Edman degradation. A purification efficiency of 476.1 fold enzymatic activity increase with 48.3% recovery was obtained by using this protocol to purity nattokinase at lab level. The efficiency was 428.1-fold with 42.6% recovery at industrial compatible pilot scale (60-fold amplification). The efficiency was 329.7-fold with 42.7% recovery for purification of fibrinolytic enzyme produced by Bacillus tequilensis, 221.7-fold with the recovery of 32.5% for purification of fibrinolytic enzyme produced by Bacillus amyloliquefaciens and 288.5 fold with 38.7% recovery for purification of fibrinolytic enzyme produced by Bacillus cereus. The purification fold of most current protocols used for nattokinase and other fibrinolyitc enzymes purification was lower than 100 and the recovery fall in between 6.28% to 80%. Thus, the protocol established in this study has a very high purification efficiency. The result of intrinsic stabilizing factor identification shown both starch and levan have the stabilizing effect on nattokinase at low pH environment. The stabilizing ability of starch is much higher than levan, and was retained even hydrolyzed by amylase. The active concentration range of starch was from 20 and up to 500 æg/ml at the pH range of 4-5.

Thesis (doctoral)--Lund University, 1997. / Added t.p. with thesis statement inserted.

Thesis (doctoral)--Lund University, 1997. / Added t.p. with thesis statement inserted.

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

Background: Advance in cardiac intervention improved the survival of patients with congenital heart diseases (CHD). However, they may have propensity of thromboembolism and the use of antithrombotic agents was generally based on small studies and consensus opinion. Objective: To systematically review the current literature on the efficacy and safety of various antithrombotic agents in patients with CHD. Methods: Studies published in English during the period 1990 – 2012 were identified using keyword search from PubMed, Medline, EMBase, and Cochrane Library. Additional search from reference sections of the articles and clinical trial registry was performed. Data extracted included: type of studies, number of patients, follow-up period during which the patients were on the antithrombotic agents, number of thromboembolic (TE) events, and all, major and minor bleeding events. Event rate as the proportion of events of the patients and event per 100 patients-year were obtained for respective antithrombotic agent in each study. Composite event rate and event per 100 patients-year were estimated after weighting. Results: Forty studies consisted of 5144 patients were reviewed. Observation period of 8916.6 years was available in 25 studies. Diagnostic categories included: Fontan operation 15, systemic-to-pulmonary artery shunt 7, mechanical valve 8, atrial septal defect occlusion device 2, cyanotic heart 1, mixed 7. Antithrombotic prophylaxis was not used in 13 studies, warfarin in 26, aspirin alone in 22, combined aspirin and dipyridamole in 2. Clopidogrel with concomitant antithrombotic agents was reported in 5 studies. Overall composite TE event rate was 3.9% (95% CI 2.3 – 5.4%) and that of all bleeding rate was 2.8% (95% CI 0 – 5.5%), with 1.4% (95% CI 0.0 – 2.6%) for major and 2.2% (95% CI 0.0 – 4.3%) for minor bleeding. Composite TE rate for no prophylaxis (9.6%; 05% CI 3.7 – 15.5%) was significantly greater than that of warfarin (1.7%; 95% CI 0.1 – 3.3%) and aspirin (1.3%; 95% CI 0.0 – 3.0%). Both TE and all bleeding rate showed no difference between warfarin and aspirin, while major bleeding tended to be higher in warfarin than aspirin(0.9% vs 0.0%, p=0.06). Fontan patients had overall TE rate of 2.7% (95% CI 0.1 – 5.4%). Patients with no prophylaxis (10.2%; 95% CI 9.2 – 18%) had significantly greater TE rate than warfarin (1.4%; 95% CI 0.0 – 0.4%) or aspirin (1.2%; 95% CI 0.0 – 3.0%). All bleeding rate in Fontan patients was 0.5% (95% CI 0.0 – 4.3%). Both TE ad bleeding rates showed no difference between warfarin and aspirin. Overall TE rate for shunt was 7.2% (95% CI 3.7 – 14.3%), being similar between aspirin group and no antithrombotic group. Patients with mechanical valves had TE rate of 7.3% (95% CI 2.9 – 11.6%) and all bleeding rate of 7.2% (95% CI 4.2 – 10.2%). There was no statistical difference between warfarin and APA group. Patients with ASD occlusion device has TE rate of 0.1% (95% CI 0.0 – 0.2%). No bleeding event was reported in the studies. Conclusion: Patients with congenital heart diseases were at risk of developing thromboembolism which justified the use of anti-thrombotic prophylaxis. Further studies relating the thromboembolic risk profile of patients with CHD to the efficacy of anti-thrombotic agents might help in selection of anti-thrombotic agents. / published_or_final_version / Community Medicine / Master / Master of Public Health