Thesis (M.D.)—Boston University

A comparison has been made of the formate-C¹⁴ incorporation into the nucleic acid purines and thymine of regenerating rat liver and Novikoff hepatoma in vivo. The effects of these tissues on one another, and on the host tissues has been studied. The utilization of formate by the nucleic acids of Novikoff hepatoma and regenerating rat liver was not significantly altered in animals containing both of these rapidly dividing tissues. The results indicated that the demand for formate by one of the rapidly growing tissues did not lower the uptake of formate by the nucleic acids of the other tissue. Furthermore it was indicated that nucleic acid synthesis in regenerating liver did not alter the synthesis of nucleic acids in other tissues. Regenerating liver and Novikoff hepatoma had no effect on the nucleic acid metabolism of the host tissues of animals bearing one or both of these tissues. These results are not completely in agreement with those reported in the literature. In a preliminary experiment a radioactive suspension of Novikoff hepatoma was transplanted into rats. Twenty percent of the injected radioactivity was recovered in the urine during the first 24 hours of tumor growth. The specific activities of the nucleic acid bases of the tumor, obtained after 24 hours of growth, were negligible. These findings indicated that the nucleic acids of the donor tumor suspension were not utilized in the synthesis of the nucleic acids of the growing tumor. / Medicine, Faculty of / Biochemistry and Molecular Biology, Department of / Graduate

No description available.

The most important and novel finding of this work was enhanced liver Kupffer cell phagocytic and metabolic function by hypervitaminosis A. An animal model of hypervitaminosis A was developed in male Sprague-Dawley rats gavaged with 250,000 I.U. retinol/Kg body weight/day for 3 weeks. Presence of hypervitaminosis A was indicated by characteristic changes in the fur coat, presence of brittle bones and spontaneous fractures and a significant increase in plasma and liver concentrations of retinyl palmitate while retinol levels remained the same as in controls. Hypervitaminosis A did not cause severe liver abnormalities as reflected by normal plasma glutamate pyruvate transaminase activity and bilirubin. Hepatic blood flow and portal pressure were also normal. Liver microsomal cytochrome P-450 was decreased while malondialdehyde, a by-product of lipid peroxidation, was increased by the Vitamin A treatment. Examination of liver tissue by light microscopy showed no signs of liver cell injury. The main change was a marked increase in size of the fat or Vitamin A storing cells. Although hypervitaminosis A itself did not cause severe liver damage, pretreatment with high doses of Vitamin A severely potentiated liver injury by known hepatotoxicants such as carbon tetrachloride, endotoxin and acetaminophen. The potentiation of hepatotoxicity was determined by activity of glutamate pyruvate transaminase in plasma as well as by histological examination of liver tissue. Measurement of clearance from blood of indocyanine green and ⁹⁹ᵐTc-disofenin indicated this hepatocyte function was normal. Kupffer cell phagocytic function was enhanced in hypervitaminosis A as determined by clearance from blood of ⁹⁹ᵐTc-sulfur colloid. In vitro, there was also evidence that treatment with high doses of Vitamin A activated or enhanced Kupffer cell function. Kupffer cells from control and Vitamin A treated rats were isolated by enzymatic dispersion, purified by centrifugal elutriation, and placed in culture. Activation was indicated by (1) increased phagocytosis of ⁵¹Cr-labeled opsonized sheep red blood cells (2) enhanced release of superoxide anion and (3) enhanced production of tumor cytolytic factor by Kupffer cells from Vitamin A treated rats. Stimulation of Kupffer cell function in hypervitaminosis A seemed to be via lymphokines produced by lymphocytes in response to the excess Vitamin A. We propose that activated Kupffer cells may play an important role in liver injury in hypervitaminosis A.

The cholestatic liver diseases include Primary Biliary Cirrhosis (PBC) and Primary Sclerosing Cholangitis (PSC). The aetiologies of PBC and PSC are not yet known but it is thought that there are both inherited and environmental factors associated with pathogenesis. In this thesis, I set out to explore the immunologic and virologic basis of cholestatic liver diseases. In recent years a novel human betaretrovirus has been proposed as an antigenic target in PBC. Using separate T cell assays, I analysed responses to both autoantigens and foreign antigens in parallel, backed up with a molecular approach. I have shown that although there is definite evidence of prior encounter with HBRV peptides at the immunologic level the virus is not closely associated with the pathogenesis of PBC. I have shown that there are links between the composition of the cellular infiltrate and the histologic scores as well as the clinical status. In PBC, the accumulation of CD8+ cells in particular correlates with liver fibrosis stage and Foxp3 cells may have an influence on portal and lobular inflammation. In PSC, the frequency of T helper cells and B cells correlate with alkaline phosphatase and liver stage. This may indicate a closer relationship between tissue histochemistry results and fibrosis and clinical markers in PSC than in PBC and may not simply be a result of portal tract inflammation but be associated with disease pathogenesis. The quality of life tool PBC-40 showed similar results to the original Newcastle cohort. Fatigue is the symptom with the greatest apparent impact and there was no association found between symptoms and biological parameters of disease activity and severity. In PSC, there was a negative correlation between the average CD8 count per infiltrate and the emotional and social domain suggesting alterations in CD8 liver cell counts may have an influence on human behaviour or vice versa. Overall these data provide new insight into the pathogenesis of both PBC and PSC, and provide new avenues for immunologic analysis of these diseases in future.

by Lau Tze Chin, Gene. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1991. / Includes bibliographical references (Leaves 170-195). / Abstract --- p.1 / Acknowledgement --- p.3 / List of tables --- p.4 / List of figures --- p.6 / List of abbreviations --- p.7 / Chapter Chapter One - --- Introduction --- p.9 / Chapter 1.1. --- Historical Aspects --- p.9 / Chapter 1.2. --- Classification of hepatitis B virus --- p.12 / Chapter 1.2.1. --- Hepadnaviruses --- p.12 / Chapter 1.2.2. --- Comparative properties of hepadnaviruses --- p.13 / Chapter 1.2.2.1. --- Physical properties --- p.13 / Chapter 1.2.2.2. --- Genetic relatedness --- p.15 / Chapter 1.2.2.3. --- Pathogenesis --- p.16 / Chapter 1.3. --- Structural and morphological properties of HBV --- p.17 / Chapter 1.4. --- Molecular biology of HBV --- p.20 / Chapter 1.4.1. --- Molecular structure of HBV --- p.20 / Chapter 1.4.1.1. --- Biochemistry of the virion envelope --- p.20 / Chapter 1.4.1.2. --- The nucleocapsid --- p.21 / Chapter 1.4.1.3. --- Structural features of HBV genome --- p.23 / Chapter 1.4.2. --- Genetic organization of HBV --- p.24 / Chapter 1.4.3. --- Infection cycle of HBV --- p.29 / Chapter 1.4.3.1. --- Viral attachment and internalization --- p.29 / Chapter 1.4.3.2. --- Replication of HBV --- p.30 / Chapter 1.4.3.3. --- Gene expression and regulation --- p.31 / Chapter 1.4.3.4. --- Host-virus DNA interaction --- p.33 / Chapter 1.5. --- Epidemiology and transmission of HBV --- p.34 / Chapter 1.5.1. --- World wide prevalence --- p.35 / Chapter 1.5.1.1. --- HBsAg prevalence --- p.35 / Chapter 1.5.1.2. --- Cumulative rate of HBV infection --- p.35 / Chapter 1.5.1.3. --- Age specific pattern of HBV infection --- p.36 / Chapter 1.5.2. --- Epidemiological pattern of HBV in Hong Kong --- p.37 / Chapter 1.5.3. --- Mode of transmission --- p.38 / Chapter 1.6. --- Clinical outcomes of HBV infection --- p.38 / Chapter 1.6.1. --- Acute infection --- p.41 / Chapter 1.6.2. --- Chronic infection --- p.42 / Chapter 1.6.3. --- Primary hepatocellular carcinoma --- p.43 / Chapter 1.7. --- Laboratory diagnosis of hepatitis B --- p.44 / Chapter 1.7.1. --- The HBV markers --- p.47 / Chapter 1.7.1.1. --- HBsAg and anti-HBs --- p.47 / Chapter 1.7.1.2. --- HBcAg and Anti-HBc --- p.47 / Chapter 1.7.1.3. --- HBeAg and anti-HBe --- p.49 / Chapter 1.7.1.4. --- HBV-associated DM polymerase --- p.49 / Chapter 1.7.1.5. --- HBV-DNA --- p.49 / Chapter 1.7.2. --- Methodology in the detection of hepatitis B markers --- p.50 / Chapter 1.7.2.1. --- Direct detection of HBV and HBV antigens --- p.50 / Chapter 1.7.2.2. --- Serological detection of HBV markers --- p.51 / Chapter 1.7.2.3. --- HBV-associated DNA polymerase assay --- p.51 / Chapter 1.7.2.4. --- Molecular technique for the detection and quantitation of HBV-DNA --- p.52 / Chapter 1.8. --- Antiviral therapy in hepatitis B --- p.52 / Chapter 1.8.1. --- Therapeutic agents for treatment of HBV infection --- p.53 / Chapter 1.8.1.1. --- Steroids --- p.53 / Chapter 1.8.2.2. --- Nucleoside analogs --- p.54 / Chapter 1.8.1.3. --- Interferon --- p.55 / Chapter 1.8.2. --- Clinical trials of interferons --- p.55 / Chapter 1.9. --- Extrahepatic tissue tropism of HBV --- p.62 / Chapter 1.10. --- Objective and design of study --- p.65 / Chapter 1.10.1. --- Objectives of study --- p.65 / Chapter 1.10.2. --- Study design --- p.66 / Chapter 1.10.2.1. --- Cross-sectional study --- p.67 / Chapter 1.10.2.2. --- Longitudinal study --- p.67 / Chapter 2.1. --- Materials --- p.71 / Chapter 2.1.1. --- Patients recruitment and clinical materials --- p.71 / Chapter 2.1.1.1. --- Cross-sectional study --- p.71 / Chapter 2.1.1.2. --- Longitudinal study --- p.71 / Chapter 2.1.2. --- Bacteria] stock --- p.71 / Chapter 2.1.3. --- "Chemicals, equipments and consumables" --- p.72 / Chapter 2.1.4. --- Buffers and solutions --- p.72 / Chapter 2.1.4.1. --- Phosphate buffer saline (PBS) --- p.72 / Chapter 2.1.4.2. --- Leucocyte lysis buffer (X 5)(LLB) --- p.72 / Chapter 2.1.4.3. --- Buffer equilibrated phenol (BEP) --- p.76 / Chapter 2.1.4.4. --- Phenol-Chloroform mixture --- p.76 / Chapter 2.1.4.5. --- 3.0M sodium acetate (pH 5.2) --- p.76 / Chapter 2.1.4.6. --- Tris-EDTA buffer (pH 8.0) (TE) --- p.76 / Chapter 2.1.4.7. --- Stock salmom sperm DNA solution --- p.77 / Chapter 2.1.4.8. --- Tracking dye --- p.77 / Chapter 2.1.4.9. --- Tris-borate electrophoresis buffer (TBE) --- p.77 / Chapter 2.1.4.10. --- Luria-Bertani Broth (LB) --- p.77 / Chapter 2.1.4.11. --- Solution ] --- p.78 / Chapter 2.1.4.12. --- Solution ]] --- p.78 / Chapter 2.1.4.13. --- Potassium acetate buffer (pH 5.4) --- p.78 / Chapter 2.1.4.14. --- Column elution buffer (CEB) --- p.78 / Chapter 2.1.4.15. --- NPMEB solution --- p.79 / Chapter 2.1.4.16. --- Neutralizing solution --- p.79 / Chapter 2.1.4.17. --- Standard saline citrate (SSC) --- p.79 / Chapter 2.1.4.18. --- Denhardt solution --- p.79 / Chapter 2.1.4.19. --- Prehybridization solution (PS) --- p.80 / Chapter 2.1.4.20. --- NETFAP Solution --- p.80 / Chapter 2.1.4.21. --- Heparin solution --- p.81 / Chapter 2.1.4.22. --- Hybridization mix for oligo-nucleotide probe --- p.81 / Chapter 2.1.4.23. --- NEPS solution (pH 7.0) --- p.81 / Chapter 2.1.4.24. --- Restriction endonuclease and buffer --- p.82 / Chapter 2.2. --- Methods --- p.82 / Chapter 2.2.1. --- Sample preparations --- p.82 / Chapter 2.2.1.1. --- Isolation of plasma and peripheral blood leucocytes (PBL) --- p.82 / Chapter 2.2.1.2. --- Extraction of DNA from Peripheral blood leucocytes --- p.83 / Chapter 2.2.1.3. --- Quantitation of Peripheral blood leucocyte DNA --- p.83 / Chapter 2.2.2. --- Preparation of radio-labelled HBV-DNA probe --- p.84 / Chapter 2.2.2.1. --- Plating and selection of bacterial stock --- p.84 / Chapter 2.2.2.2. --- Growth of E. coli HB101 and amplification of pAM6 --- p.84 / Chapter 2.2.2.3. --- Harvesting of E. coli and extraction of plasmid pAM6 --- p.84 / Chapter 2.2.2.4. --- Purification of plasmid pAM6 --- p.86 / Chapter 2.2.2.5. --- Large scale isolation and purification of HBV genome from plasmid pAM6 --- p.86 / Chapter 2.2.2.6. --- Radio-labelling of HBV-DNA --- p.88 / Chapter 2.2.2.6.1. --- Nick-translation of total HBV-DNA genome --- p.88 / Chapter 2.2.2.6.2. --- Multi-primer labelling of total HBV- DNA genome --- p.88 / Chapter 2.2.2.6.3. --- End-labeling of 21-base HBV oligo- nucleotide --- p.88 / Chapter 2.2.2.6.4. --- Determination of labelling efficiency --- p.89 / Chapter 2.2.2.7. --- Purification of labelled HBV-DNA probe --- p.90 / Chapter 2.2.2.7.1. --- Total genomic HBV-DNA probe (pAM6 probe) --- p.90 / Chapter 2.2.2.7.2. --- Oligo-nucleotide HBV-DNA probe (oligo probe) --- p.90 / Chapter 2.2.3. --- Hybridization study of clinical samples --- p.91 / Chapter 2.2.3.1. --- Solution hybridization of sera samples --- p.91 / Chapter 2.2.3.2. --- Spot hybridization of sera samples --- p.91 / Chapter 2.2.3.2.1. --- "Pre-hybridization treatment of sera samples (adapted from Lin et al.,1987)" --- p.91 / Chapter 2.2.3.2.2. --- Pre-hybridization and hybridization of the membrane --- p.92 / Chapter 2.2.3.2.3. --- Washing of membrane --- p.92 / Chapter 2.2.3.2.4. --- Final treatment and autoradiography: --- p.92 / Chapter 2.2.3.3. --- Quantitation of HBV-DNA in the sera samples: --- p.93 / Chapter 2.2.4. --- Assay for serological Hepatitis B marker --- p.93 / Chapter Chapter Three - --- Results --- p.93 / Chapter 3.1. --- Preparation of HBV-DNA probes --- p.95 / Chapter 3.2. --- Radiolabelling of HBV-DNA --- p.95 / Chapter 3.3. --- Hybridization methodology --- p.98 / Chapter 3.4. --- Comparison of the performance of HBV-DNA probes --- p.100 / Chapter 3.4.1. --- Quantitation of serum HBV-DNA --- p.100 / Chapter 3.4.2. --- Comparative hybridization performance of different HBV-DNA probes --- p.105 / Chapter 3.5. --- Clinical application of HBV-DNA probe:Detection of HBV-DNAin serum and peripheral blood leucocytes (PBL) --- p.109 / Chapter 3.5.1. --- Cross-sectional study --- p.112 / Chapter 3.5.1.1. --- Frequency of HBV-DNA detection in relation to different clinical manifestations --- p.112 / Chapter 3.5.1.2. --- Frequency of HBV-DNA detection in relation to the serological status --- p.114 / Chapter 3.5.1.3. --- Distribution of serum and PBL HBV-DNA level in chronic hepatitis B patients in relation to the different HBV-related manifestations --- p.119 / Chapter 3.5.2. --- Longitudinal study of patients with chronic hepatitis B under interferon therapy with prednisolone pretreatment --- p.123 / Chapter 3.5.2.1. --- Features of patients under study --- p.123 / Chapter 3.5.2.2. --- Correlation between the occurrence of HBV- DNA and HBeAg in serum --- p.123 / Chapter 3.5.2.3. --- Outcome of clinical trial: --- p.126 / Chapter 3.5.2.3.1. --- Number of patients responding to therapy: --- p.126 / Chapter 3.5.2.3.2. --- Variation in serum HBV markers during the course of study --- p.128 / Chapter 3.5.2.3.3. --- Change of HBV-DNA statusin peripheral blood leucocytes --- p.134 / Chapter Chapter Four - --- Dicussion --- p.140 / Chapter 4.1. --- Preparation of HBV-DNA hybridization probes --- p.140 / Chapter 4.1.1. --- Source of HBV-DNA --- p.140 / Chapter 4.1.2. --- Raidolabelling of HBV-DNA --- p.141 / Chapter 4.2. --- Hybridization methodology --- p.141 / Chapter 4.2.1. --- Optimization of hybridization conditions --- p.141 / Chapter 4.2.2. --- Comparison of the performance among different HBV- DNA probes --- p.144 / Chapter 4.3. --- Detection of HBV-DNA in clinical serum samples --- p.148 / Chapter 4.3.1. --- Crossectional study of patients with various categories of HBV related diseases --- p.148 / Chapter 4.3.1.1. --- HBV-DNA detection in serum --- p.148 / Chapter 4.3.1.2. --- Detection of HBV-DNA in peripheral blood mononuclear cells --- p.153 / Chapter 4.3.2. --- Longitudinal studies of patients undergoing antiviral therapy --- p.159 / Chapter 4.3.2.1. --- Serum HBV-DNA and HBeAg --- p.159 / Chapter 4.3.2.2. --- HBV-DNA in peripheral blood leucocytes --- p.163 / Conclusion --- p.166 / Future perspectives --- p.168 / References --- p.170

by King Yeung Wong. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1999. / Includes bibliographical references (leaves 143-148). / Abstracts in English and Chinese. / Title Page --- p.i / Acknowledgement --- p.ii / List of Abbreviations --- p.iii / Table of contents --- p.v / Abstract --- p.viii / Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Liver diseases --- p.1 / Chapter 1.2 --- Current treatments of liver diseases --- p.3 / Chapter 1.3 --- Schizandrae --- p.5 / Chapter 1.3.1 --- Chemistry of Schizandrae (Wuweizi) --- p.6 / Chapter 1.3.2 --- Pharmacology of Wuweizi --- p.8 / Chapter 1.3.2.1 --- Hepato-protective effect of Wuweizi --- p.9 / Chapter 1.3.3 --- Toxicology and side-effects of Wuweizi --- p.11 / Chapter 1.4 --- Carbon tetrachloride (CC14) intoxication --- p.12 / Chapter 1.5 --- Hepatic drug metabolism: essential factors --- p.13 / Chapter 1.6 --- Aim --- p.14 / Chapter 2 --- Phase I metabolism --- p.15 / Chapter 2.1 --- Introduction --- p.15 / Chapter 2.2 --- Materials and Methods --- p.18 / Chapter 2.2.1 --- Animals --- p.18 / Chapter 2.2.2 --- Chemicals --- p.18 / Chapter 2.2.3 --- Instruments --- p.19 / Chapter 2.2.4 --- Preparation of Schizandra seed extract --- p.19 / Chapter 2.2.5 --- Animal model of liver damages --- p.20 / Chapter 2.2.6 --- Evaluation of protective effect of Schizandra extract --- p.22 / Chapter 2.2.7 --- Evaluation of healing effect of Schizandra extract --- p.24 / Chapter 2.2.8 --- Extraction of antipyrine from blood and urine --- p.26 / Chapter 2.2.9 --- TLC method for quantitative analysis of antipyrine --- p.26 / Chapter 2.2.10 --- Analysis of pharmacokinetic parameters of antipyrine --- p.27 / Chapter 2.2.11 --- Statistical analysis --- p.28 / Chapter 2.3 --- Results --- p.30 / Chapter 2.3.1 --- Effect of CCI4 and Schizandra seed extract on antipyrine metabolism --- p.30 / Chapter 2.4 --- Discussion --- p.41 / Chapter 3 --- Phase II metabolism --- p.44 / Chapter 3.1 --- Introduction --- p.44 / Chapter 3.2 --- Materials and Methods --- p.46 / Chapter 3.2.1 --- Chemicals --- p.46 / Chapter 3.2.2 --- Preparation of Schizandra extract --- p.46 / Chapter 3.2.3 --- Preparation of Salicylamide solution (for injection) --- p.47 / Chapter 3.2.4 --- Preparation of 2，4-dinitrophenylhydrazine solution --- p.47 / Chapter 3.2.5 --- Animal groups --- p.47 / Chapter 3.2.6 --- Animal model of liver damage --- p.48 / Chapter 3.2.7 --- Evaluation of the hepato-protective effect of Schizandra extract --- p.49 / Chapter 3.2.8 --- Determination of serum glutamate pyruvate transaminase (SGPT/ALT) and serum glutamate oxaloacetate transaminase (SGOT/AST) --- p.50 / Chapter 3.2.9 --- Salicylamide adminstration and plasma collection --- p.51 / Chapter 3.2.10 --- Procession of plasma and urine samples --- p.52 / Chapter 3.2.11 --- HPLC Analysis --- p.54 / Chapter 3.2.12 --- Preparation of liver microsomes --- p.55 / Chapter 3.2.13 --- Determination of cytochrome P450 --- p.56 / Chapter 3.2.14 --- Determination of protein content of the liver microsomes --- p.57 / Chapter 3.2.15 --- Data Analysis --- p.58 / Chapter 3.2.16 --- Statistical Analysis --- p.58 / Chapter 3.3 --- Results --- p.60 / Chapter 3.3.1 --- Liver enzyme levels --- p.60 / Chapter 3.3.2 --- Phase II metabolism profile of salicylamide --- p.61 / Chapter 3.3.3 --- Cytochrome P450 content of liver --- p.64 / Chapter 3.4 --- Discussion --- p.65 / Chapter 3.4.1 --- Liver enzyme assay --- p.65 / Chapter 3.4.2 --- Cytochrome P450 activity --- p.67 / Chapter 3.4.3 --- Hepatic metabolism of salicylamide --- p.68 / Chapter 3.4.4 --- Effect of CC14 intoxication on Phase II metabolism --- p.71 / Chapter 3.4.5 --- Wuweizi actions on Phase II metabolism --- p.73 / Chapter 4 --- Protein binding --- p.102 / Chapter 4.1 --- Introduction --- p.102 / Chapter 4.2 --- Materials and Methods --- p.104 / Chapter 4.2.1 --- Chemicals --- p.104 / Chapter 4.2.2 --- Instruments --- p.105 / Chapter 4.2.3 --- Preparation of Warfarin sodium solution --- p.105 / Chapter 4.2.4 --- Animal groups --- p.106 / Chapter 4.2.5 --- Equilibrium dialysis --- p.106 / Chapter 4.2.5.1 --- Equilibration time --- p.106 / Chapter 4.2.5.2 --- Equilibrium dialysis of different warfarin concentration --- p.107 / Chapter 4.2.6 --- High performance liquid chromatography analysis of warfarin --- p.108 / Chapter 4.2.7 --- Calibration curve --- p.109 / Chapter 4.3 --- Results --- p.111 / Chapter 4.3.1 --- Equilibriation time --- p.111 / Chapter 4.3.2 --- Calibration curve --- p.111 / Chapter 4.3.3 --- Free concentration of warfarin --- p.112 / Chapter 4.4 --- Discussion --- p.114 / Chapter 4.4.1 --- Effect of CCl4 intoxication on free percentage of warfarin --- p.114 / Chapter 4.4.2 --- Effcct of wuweizi cxtract on free percentage of warfarin --- p.115 / Chapter 4.4.2.1 --- Depletion of plasma albumin concentration --- p.116 / Chapter 4.4.2.2 --- Displacement of warfarin by WWZ extract --- p.117 / Chapter 4.4.3 --- Concentration dependent protein binding --- p.118 / Chapter 5 --- Hepatic blood flow --- p.124 / Chapter 5.1 --- Introduction --- p.124 / Chapter 5.2 --- Materials and Methods --- p.126 / Chapter 5.2.1 --- Chemicals....: --- p.126 / Chapter 5.2.2 --- Instruments --- p.126 / Chapter 5.2.3 --- Preparation of indocyanine green (ICG) solution --- p.126 / Chapter 5.2.4 --- Preparation of Schizandra seed extract --- p.127 / Chapter 5.2.5 --- Animals groups --- p.127 / Chapter 5.2.6 --- Animal model of liver damage --- p.128 / Chapter 5.2.7 --- Evaluation of hepato-protective effect of Schizandra extract --- p.129 / Chapter 5.2.8 --- Evaluation of healing effect of Schizandra extract --- p.129 / Chapter 5.2.9 --- Quantitative analysis of ICG in plasma by UV spectroscopy --- p.130 / Chapter 5.2.10 --- Analysis of pharmacokinetic parameters of ICG --- p.131 / Chapter 5.2.11 --- Statistical analysis --- p.132 / Chapter 5.3 --- Results --- p.133 / Chapter 5.4 --- Discussion --- p.135 / Chapter 5.4.1 --- Effect of CCl4 intoxication on hepatic blood flow --- p.135 / Chapter 5.4.2 --- Effect of WWZ pretreatment on hepatic blood flow --- p.135 / Chapter 5.4.3 --- Effect of WWZ healing on hepatic blood flow --- p.136 / Chapter 6 --- General conclusion --- p.139 / Significance of the study --- p.141 / References --- p.143

No description available.

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

A study of the causes of liver enlargement amongst black patients at King Edward VIII Hospital, Durban, South Africa has revealed that congestive cardiac failure (36.7%), amoebic liver abscess (7.1%), hepatocellular carcinoma (5.8%) and cirrhosis (5.4%) are the most common causes in this population. Liver biopsy was needed to determine the cause in 28.7% of patients studied. The diagnostic yield of percutaneous liver biopsy was increased by obtaining 2 or 3 consecutive specimens for histological examination by redirecting the biopsy needle through a single entry site. This benefit was achieved without an increase in morbidity or mortality. Fatalities and complications associated with liver biopsy were more frequent at this hospital than in hospitals in Europe, The United Kingdom and North America. The complication rates after percutaneous or peritoneoscopic biopsy were 2.0% and 2.3% respectively. A total of 6 deaths was recorded. The morbidity and mortality rates were not increased when more than one specimen was taken during percutaneous biopsy. In the majority of patients in whom biopsy was carried out, after-care was either non-existent or inadequate. The "Tru-Cut" needle was used for all percutaneous liver biopsies at King Edward VIII Hospital. Two techniques, including the method recommended by the manufacturer, have been found to be incorrect; the needle must be used correctly if an adequate biopsy specimen is to be obtained for histological examination and if serious complications are to be avoided. Hepatic tuberculosis was diagnosed in 9% of patients with unexplained hepatomegaly who were subjected to liver biopsy. This disease did not yield any consistent clinical findings. In addition, liver function tests were of little diagnostic value and results of hepatic imaging techniques were often normal. Accordingly, a high index of suspicion is needed and liver biopsy is essential in patients with unexplained hepatomegaly or hepatospienomegaly, or pyrexia of unknown origin since biopsy provides the only means of diagnosing hepatic tuberculosis. The accuracy of both ultrasonography and scintigraphy in distinguishing between normal and diseased livers was low (68% and 74% respectively). These techniques performed better at detecting focal than diffuse liver disease; the sensitivity of ultrasonography and scintigraphy in focal and diffuse disease were 88% and 92%, and 27% and 54% respectively. The specificity of both procedures was high for both types of liver disease (range 91-96%). Overlap between the ultrasonographic features of amoebic liver abscess, hepatocellular carcinoma and metastatic carcinoma resulted in a correct final diagnosis being made in only 81% of patients with amoebic liver abscess, 29% with hepatocellular carcinoma and 43% of patients with metastatic carcinoma who had an ultrasound scan. Neither technique was capable of determining the cause of diffuse liver disease. Therefore, when diffuse parenchymal liver disease is suspected, liver biopsy is needed to determine the presence and nature of the disease. In addition, liver biopsy or aspiration is usually required to determine the cause of focal disease in selected patients in whom space-occupying lesions are detected on hepatic imaging studies. / Thesis (M.D.)-University of Natal, Durban, 1990.