Part 1 Pathophysiology: Anatomy of the Liver: Normal Histology and Ultrastructure: Carbohydrate Metabolism in Liver Disease: Plasma Lipoproteins and the Liver: Protein Metabolism and the Liver: Nutritional Aspects of Liver Disease: The Liver and the Endocrine System: Haematological Disorders in Liver Disease: Immunological Aspects of Liver Disease: Physical Aspects of Hepatic Regeneration: Regulatory Mechanisms in Hepatic Regeneration: The Physiology of the Gallbladder and Extrahepatic Biliary Tree: Bile Acids in Liver and Biliary Disease: Bilirubin Metabolism and Hyperbilirubinaemic Disorders: Cholestasis: Haem Metabolism and the Porphyrias: The Liver and Response to Drugs. Part 2 Diagnosis and Management: Assessment of Liver Function: Liver Biopsy: Some Aspects of Ultrastructural Pathology: Radionuclide Imaging: Ultrasound Imaging: Computed Tomography: Magnetic Resonance Imaging: Angiography: Endoscopic-Radiological Examination and Therapy in Biliary Tract Disease: Peritoneoscopy: Investigation of the Jaundiced Patient: Acute Liver Failure: Acute Viral Hepatitis: Chronic Hepatitis: Cirrhosis. An Appraisal: Primary Biliary Cirrhosis: Alcoholic Liver Disease: Wilson's Disease: Haemochromatosis and Related Iron Storage Diseases: Hepatic Changes in Systemic Disease: The Liver in Infection: Hepatic Tumours: Treatment of Liver Tumors: Involvement of the Liver By Lymphoreticular Disease: Liver Disease in Pregnancy: Alpha-1-Antitrypsin Deficiency and Liver Disease: Paediatric Liver Disease. Medical and Surgical Aspects: The Liver and Drugs: Portal-Systemic Encephalopathy: Portal Hypertension. Pathology Diagnosis and Treatment: The Surgery of Portal Hypertension.
Decreased albumin synthesis by hepatocytes in liver injury is thought to occur in response to Kupffer cell-derived acute-phase cytokines. In this study we used hepatocytes maintained in a differentiated phenotype, by culture on a laminin-rich gel substratum (Engelbreth-Holm-Swarm matrix), to investigate the effects of Kupffer cell-conditioned medium and purified cytokines (interleukin-1, interleukin-6 and tumor necrosis factor-alpha) on albumin synthesis. Kupffer cell-conditioned medium caused a reversible decrease in albumin synthesis to 64.7% of control (p < 0.01, Wilcoxon's rank sum test, n = 11) on day 2. Repeated doses caused further dose-dependent reversible responses. The same result was obtained when protease inhibitors (alpha-1-antitrypsin and alpha-2-macroglobulin) were added to Kupffer cell-conditioned medium (n = 3), thus eliminating the potential effect of matrix degradation. Pure interleukin-1, interleukin-6 and tumor necrosis factor-alpha also inhibited albumin synthesis (p < 0.05, Wilcoxon's rank sum test, n = 5), interleukin-6 having the greatest effect. After exposure to interleukin-1 (30 U.ml-1) and tumor necrosis factor-alpha (300 U.ml-1), decreased albumin synthesis was followed by a rebound increase (n = 3). Our results support the hypothesis that reduced albumin synthesis in the acute-phase response is modulated by cytokines released from Kupffer cells. Moreover, our results suggest that hepatocytes may exhibit a compensatory increase in albumin synthesis after cytokine withdrawal. These findings may be of physiological importance in the recovery from injury and the acute-phase response in vivo.
Ora; ciprofloxacin was studied as a prophylactic antimicrobial agent in high- and low-risk patients undergoing endoscopic retrograde cholangiography. Ciprofloxacin appeared to be effective, good serum levels were attained, and the drug compared favourably on grounds of cost and convenience with a parenterally-administered cephalosporin.
A 30 year old bodybuilder who had been taking anabolic steroids for 18 months presented with bleeding oesophageal varices. Serious liver disease secondary to anabolic steroids including peliosis hepatis, nodular hyperplasia and malignant change is well recognized. We report what is, to our knowledge, the first case of bleeding oesophageal varices associated with the use of anabolic steroids.
The epidemiology of HAV, HBV, HCV, HDV and HEV is compared. Spread of HAV and HEV is by the faecal/oral route whereas HBV, HCV and HDV are spread by blood or blood products. HEV is more likely to produce large epidemics than HAV but sporadic cases also occur. HBV, HCV and HDV all occur after blood transfusion, in haemophiliacs and intravenous drug abusers but they differ in their geographical distribution and in the frequency of perinatal transmission which is only common with HBV. Superinfection and interaction between these viruses is discussed.
The chronic fatigue syndrome is a heterogeneous disorder characterized by easy fatigability, feverishness, diffuse pains, and depression. Many patients also report inhalant, food, or drug allergies. This article reviews the clinical features of the syndrome and hypotheses of its pathogenesis, especially those regarding the Epstein-Barr virus and cellular immune mechanisms. Also summarized are recent studies of the validity of atopic complaints in the syndrome. The results of epicutaneous skin testing demonstrated a high correlation with history in 24 patients Atopy coexists with the chronic fatigue syndrome in >50% of patients.
Reactive oxygen intermediates released by activated hepatic macrophages have been implicated in the pathogenesis of a rat model of liver injury induced by sequential administration of Corynebacterium parvum and endotoxin. In this model, C. parvum causes extensive infiltration of the liver with activated macrophages, but severe liver injury occurs only after subsequent exposure to endotoxin. We have therefore investigated the effects of endotoxin on the release of reactive oxygen intermediates by C. parvum-activated hepatic macrophages. After in vitro exposure to zymosan, opsonized zymosan, or phorbol myristate acetate, hepatic macrophages isolated from C. parvum- and endotoxin-treated rats demonstrated significantly (1.5-2-fold) increased release of superoxide and oxidation of [1-14C]glucose via the hexose monophosphate shunt compared with hepatic macrophages isolated from C. parvum- and saline-treated control rats. These results indicate that endotoxin enhances the state of activation of hepatic macrophages already partially activated by C. parvum. We suggest that the increased release of reactive oxygen intermediates by these cells promotes liver injury in this model.
Superoxide production by stimulated phagocytes is commonly measured by reduction of ferricytochrome C, with specificity of the assay assumed if the reaction is inhibited by superoxide dismutase (SOD). Most preparations of ferricytochrome C contain a small proportion in the reduced (ferro) form, and this is also formed by the reaction of ferricytochrome C with superoxide. The generation of other reactive oxygen intermediates, such as hydrogen peroxide or hydroxyl radical, could cause oxidation of ferrocytochrome C and consequent underestimation of superoxide production. In support of this, it has been demonstrated that exogenous catalase enhanced the reduction of ferricytochrome C by phorbol myristate acetate (PMA)-stimulated human monocytes. Control experiments confirmed that this was due to enhanced detection rather than increased production of superoxide. In addition, SOD was found to promote oxidation of ferrocytochrome C by PMA-stimulated human monocytes, but this was also inhibited by catalase. These effects of catalase and SOD on ferricytochrome C reduction/ferrocytochrome C oxidation were also demonstrated when superoxide was produced independently of monocytes by a xanthine and xanthine oxidase generating system. It is concluded that the assay of superoxide, using 'SOD inhibitable' reduction of ferricytochrome C, underestimates superoxide production.
In summary, there has been a dramatic increase in our understanding of food allergy as a result of research in immune mechanisms and clinical studies over the last decade. The subject has been comprehensively reviewed in a major new publication (Brostoff and Challacombe, 1986).
A non-operative method of palliation in malignant obstructive jaundice was used in 14 patients in whom a biliary stent could not be placed endoscopically. A guide wire was manipulated through the obstructing lesion through the percutaneous transhepatic route and retrieved through an endoscope. The stent was then fed through the endoscope over the guide wire and across the biliary stricture. There were no early complications, and worth-while palliation was obtained in most cases. The success rate for placing an endoscopic stent increased in this unit from 69 to 97% with the introduction of this technique.
A radiolabelled 50-base oligonucleotide complementary with the measles virus gene encoding the nucleocapsid was used as a probe to identify persistent measles virus genome in the lymphocytes from patients with autoimmune chronic active hepatitis (AICAH). Positive hybrids were found in 12 of 18 patients, and correlated strongly with high antibody titres to measles. Among the 45 controls, positive hybrids were found in 1 patient with measles, 1 of 3 patients with systemic lupus erythematosus, and 2 of 4 patients with cryptogenic cirrhosis. Persistence of part of the measles virus genome in AICAH may have important implications in the pathogenesis of the liver disease, and possibly in other disorders such as systemic lupus erythematosus, multiple sclerosis, and Paget's disease where an abnormal immune response to measles has been observed.