Cover -- Half-title -- Title -- Copyright -- Contents -- Contributors -- Preface -- Part 1 Assessing and utilizing the diagnostic or prognostic power of biomarkers -- 1 Evidence-based medicine: evaluation of biomarkers -- Evidence-based medicine -- Systematic review -- Size -- Expressing results -- Evidence-based laboratory medicine -- Size -- Expressing results -- New paradigms for diagnostic test evaluation -- CARE -- Conclusions -- REFERENCES -- 2 Development of biomarkers: the industrial perspective -- The laboratory -- Testing near the patient -- Home testing -- Who is the customer? -- The future - for the IVD industry and the professions it supplies -- Conclusion -- REFERENCES -- 3 Statistical approaches to rational biomarker selection -- Introduction -- Motivation for the use of intermediate end-points or surrogates -- Defining intermediate end-points or surrogates -- Validating intermediate end-points or surrogates -- Assessing markers for diagnosis -- REFERENCES -- 4 Using intelligent systems in clinical decision support -- Introduction -- Clinical decision support systems -- System definitions -- Decision support in the diagnostic process -- Specific systems -- Function: test selection -- Liver Unit Medical Protocol System -- Function: test interpretation -- Pathology Expert Interpretative Reporting System -- Tumour marker interpretation -- Function: diagnostic risk analysis -- TeleGastro -- Trisomy-21 risk analysis -- Barriers to use -- Availability of outcome data -- Technical issues -- Access to clinical information -- Professional needs and acceptance -- Evaluation and accreditation -- Potential for development -- REFERENCES -- Part 2 Biomarkers of kidney disease and dysfunction -- 5 Biomarkers in renal disease -- Glomerular filtration rate -- Glomerular permeability -- Tubular damage -- Nephrotoxicity -- Vesicouretic reflux.

Matrix turnover and fibrosis -- Biomarkers and complications of renal disease -- Cardiovascular risk stratification -- Metabolic bone disease -- Anaemia and renal failure -- Conclusions -- REFERENCES -- 6 The genetics of renal disease -- Introduction -- Genetic diagnosis in inherited kidney disorders -- Cystic kidney diseases -- Alport's syndrome -- von Hippel-Lindau disease -- Anderson-Fabry disease -- Genetic counselling and prenatal diagnosis in inherited kidney diseases -- Multigenic approach: from modifier genes to SNPs -- REFERENCES -- 7 Early markers of nephrotoxicity for environmental and occupational monitoring -- Introduction -- The nephrotoxic cascade -- Application to environmental and occupational health studies -- Longitudinal studies -- New biomarkers -- Cellular effects of nephrotoxins -- Choice of biomarker -- Difficulties in screening populations -- Future studies -- REFERENCES -- 8 The early detection of renal impairment in diabetes mellitus. The case for microalbuminuria and other biomarkers -- The structural basis for renal disease -- Glycaemic control, the main metabolic basis -- Normoalbuminuria, microalbuminuria and macroalbuminuria -- Estimation of GFR and renal function -- Genetic markers, family history and birth weight -- Blood pressure level, the main haemodynamic basis -- Cation cell transporters -- Renin and prorenin and the renin angiotensin system -- Endothelial dysfunction and homocysteinaemia -- Insulin resistance -- Lipid abnormalities -- Other concomitant microvascular lesions and cardiovascular disease -- Smoking -- Treatment options: based on biomarkers and clinical course -- Conclusions -- REFERENCES -- Part 3 Biomarkers of bone disease and dysfunction -- 9 Bone turnover markers in clinical practice -- Introduction -- Osteocalcin -- Serum bone alkaline phosphatase -- Crosslinks -- Predicting rate of bone loss.

Predicting risk of fracture -- Predicting response to treatment -- Monitoring response to therapy -- Day to day variability of bone turnover markers -- Circadian variation -- Growth and ageing -- Menstrual cycle -- Menopause -- Drugs -- Bed rest and immobility -- Fracture healing -- Conclusion -- REFERENCES -- 10 Biomarkers of bone formation -- Introduction -- Knock-out experiments and human genetic diseases -- An ideal assay for bone formation -- Markers of bone collagen biosynthesis -- Alkaline phosphatase -- Osteocalcin -- Changes in the bone formation markers with disease and therapy -- Future developments with bone formation markers -- Conclusions -- REFERENCES -- 11 Biochemical markers of bone resorption -- Introduction -- Pyridinium crosslinks -- Development of urinary crosslink assays -- Telopeptide assays -- Comparison of crosslink and telopeptide assays -- Standardization of crosslink assays -- Tartrate-resistant acid phosphatase -- Bone sialoprotein -- Conclusion -- Acknowledgement -- REFERENCES -- 12 The clinical application of biomarkers in osteoporosis -- Bone markers and fracture risk -- Bone markers to monitor antiresorptive therapy -- REFERENCES -- 13 Sources of preanalytical variability in the measurement of biochemical markers of bone turnover -- Introduction -- Preanalytical variability -- Technical aspects of preanalytical variability -- Handling, processing and storage of samples -- Timing and mode of urine collection -- Influence of diet or acute exercise -- A word about standardization -- Biological aspects of preanalytical variability -- Diurnal variation -- Day-to-day variability -- Menstrual variability -- Seasonal variability -- Growth, age and gender -- Nonskeletal diseases and clearance-related factors -- Summary -- REFERENCES -- 14 Genetic approaches to the study of complex diseases: osteoporosis.

Genetics of osteoporosis -- Genome scans and candidate genes -- Complicating factors -- Osteoporosis candidate genes: collagen type Ia1 and the vitamin D receptor -- REFERENCES -- Part 4 Biomarkers of liver disease and dysfunction -- 15 Biomarkers of hepatic disease -- Introduction -- Static tests -- Dynamic tests -- Future aspects -- REFERENCES -- 16 The immunogenetics of metabolic liver disease -- Introduction -- Immune allergic drug reactions -- Immunogenetic markers as determinants of outcome following paracetamol overdose -- Immunogenetic markers as determinants of outcome and fibrogenesis in alcoholic liver disease -- Immunogenetic markers as determinants of liver disease complicating the single gene disorders, cystic fibrosis… -- Cystic fibrosis -- Alpha-1-antitrypsin deficiency -- Conclusion -- REFERENCES -- 17 Toxicogenetic markers of liver dysfunction -- Introduction -- How can genetic diversity affect toxic liver injury? -- Metabolism: the first major determinant of toxic potential -- Cytoprotection: the second major determinant of toxic potential -- Genetic variants may encode inactive or superactive gene products -- Selection of toxicogenetic biomarkers: lessons from paracetamol toxicity -- Practical issues in selecting toxicogenetic biomarkers -- Biomarkers of paracetamol intoxication and detoxication -- Phenotypic variability -- REFERENCES -- 18 Prognosis and management of patients with acute liver failure -- Introduction -- Incidence and aetiology -- Prognosis and complications -- Time from jaundice to HE -- Aetiology, sex and age -- Clinical features -- Severe HE -- Convulsions -- Cerebral oedema -- Arterial hypotension, sepsis and lactic acidosis -- Endotoxins -- Lactate -- Haemorrhage -- Renal failure -- Biomarkers -- Single factors -- Coagulation factors -- Prothrombin time -- Alpha-l-fetoprotein -- Bilirubin.

Galactose elimination capacity -- Actin scavenger GC globulin -- Nitrogen metabolism -- Combination of factors -- Management -- Conclusion and perspective -- REFERENCES -- 19 Biomarkers in artificial and bioartificial liver support -- Introduction -- The need for biomarkers -- Biomarkers in clinical studies -- The use of the ELAD at King's College Hospital -- Cytokines -- Regeneration -- REFERENCES -- 20 Prognostic markers in liver disease -- Introduction -- Prognosis by diagnosis -- Pre-transplant survival -- Post-transplant survival -- REFERENCES -- 21 Apoptosis: biomarkers and the key role of mitochondria -- Introduction -- Caspase activation as the central execution event -- Caspase activation and the role of mitochondria -- Biomarkers of apoptosis -- Future and emerging biomarkers -- Conclusions -- REFERENCES -- 22 Liver regeneration: mechanisms and markers -- Introduction -- Experimental and clinical features -- Initiating responses -- Growth factors and priming -- TNFAlpha and IL-6 -- Termination -- Conclusions -- REFERENCES -- 23 Determinants of responses to viruses and self in liver disease -- Induction of autoimmune responses by viral infections -- Current concepts -- Molecular mimicry -- Bystander activation -- Induction of cross-reactive T cells by superantigens -- Autoimmunity in chronic hepatitis C -- Autoimmunity in chronic hepatitis D -- The role of genetic predisposition in autoimmune diseases -- Known risk factors associated with AIH -- Female gender -- The HLA A1-B8-DRB1*0301 and the HLA DRB1*0401 haplotypes -- Polymorphisms in the human complement C4 genes -- The - 308A allele of tumour necrosis factor Alpha -- Cytotoxic T lymphocyte antigen 4 -- AIRE, a model gene for the development of organ-specific autoimmune diseases -- Summary -- REFERENCES -- 24 IL-6-type cytokines and signalling in inflammation.

IL-6 signalling: within the cytoplasm.