Cardiac biomarkers for detection of myocardial infarction: perspectives from past to present.

With great pleasure and anticipation in recognition of Clinical Chemistry's 50th anniversary, I have been able to arm-twist four talented scientists to document their impressive marks on the science of diagnostics in the field of cardiac biomarkers and detection of myocardial infarction. Their exciting discoveries and applications have dramatically influenced the fields of laboratory medicine and cardiology and have greatly influenced the care and management of thousands of patients suffering from coronary artery disease leading to acute myocardial infarction. As a matter of historical record, I owe a great deal of thanks to each one of the coauthors of this special report because each one has personally influenced my scientific career.

Carbohydrate-deficient transferrin: a marker of alcohol abuse.

Serum carbohydrate-deficient transferrin (CDT) measurement is valuable for the identification of chronic excess alcohol consumption. CDT is increased in serum in approximately 50% of those classed as heavy drinkers and 70-80% of those defined as alcoholics. With abstinence, the serum CDT concentration reverts towards normal within approximately 2 weeks.

Genetic haemochromatosis.

Genetic haemochromatosis is an autosomal recessive inherited disorder of iron metabolism due to mutation of the HFE gene. In homozygotes (1 in 300 of the UK population), this results in excessive iron absorption from the gut and its deposition in major body organs. This may give rise to fatigue, arthritis, cardiac failure, diabetes mellitus, hepatic cirrhosis or skin pigmentation, occurring predominantly in males over 50 years of age.

C-reactive protein.

C-reactive protein (CRP) is a protein whose concentration in serum is increased in response to inflammatory stimuli. Increased levels serve to identify organic disease, monitor disease activity and assist differential diagnosis. High values are observed early in bacterial infections, active rheumatoid disease, Crohn's disease, acute myocardial infarction and after major trauma.

Prostate-specific antigen and prostate cancer.

Serum prostate-specific antigen (PSA) measurement is used to investigate patients with lower urinary tract symptoms and to screen for prostatic malignancy in symptom-free males over 50 years of age. Approximately 60% of patients with early (prostate-confined) occult malignancy show increased serum PSA levels, as do some 20% of patients with prostatic symptoms from benign prostatic disease. When PSA is only slightly raised, serial PSA measurements, correction for prostatic volume and especially measurement of free (unbound) PSA (which is reduced in prostatic malignancy) may assist the differentiation of prostatic cancer from benign hypertrophy.

Biochemical identification of alcohol abuse.

Biochemical test abnormality can indicate chronic alcohol abuse with good clinical sensitivity and specificity. Serum gamma glutamyltransferase and carbohydrate-deficient transferrin are the tests most frequently abnormal.

Porphyria and its investigation.

The porphyrias are inherited disorders of haem synthesis and must be considered in the differential diagnosis of numerous disorders.

Biochemical markers of bone turnover.

Since bone markers may reflect different aspects of bone disorders and cell function, and osteolytic and osteoblastic activities may be individually or concomitantly altered, determination of more than one marker type is generally appropriate. Also, the individual markers of a particular type do not necessarily show parallelism. For example, in osteomalacia from vitamin D deficiency, bone-specific alkaline phosphatase may be grossly elevated because of enhanced osteoblastic activity, whereas the vitamin D dependent osteocalcin may be decreased.

Biochemical testing of adrenocortical function.

Disturbed adrenal function may present in various ways. Here are outlined some of the functions of the adrenals and the clinical effects of adrenal disorder, followed by a more detailed consideration of the application of laboratory tests to the identification of adrenocortical hypo- and hyperfunction.

Cardiac troponins in patients with renal dysfunction.

Cardiac troponin T (cTnT) and cardiac troponin I (cTnI) were measured in 198 patients with renal dysfunction [132 men: median (range) age 66.1 (8.2-90.

Biochemical investigation of diabetes mellitus.

Simple biochemical investigations serve to identify diabetes, can assist in its management, and facilitate the early recognition of complications. This review outlines some of the applications of various relevant test procedures.

Inter-individual and intra-individual variability of ethanol concentration-time profiles: comparison of ethanol ingestion before or after an evening meal.

1. The magnitude of the variability of ethanol absorption is an important factor for studies that seek to determine the significance of potential interactions between ethanol and drugs. The aim of this study was to determine the extent of inter- and intra-individual variability of ethanol concentration-time profiles in fasted and fed subjects.

Bone-origin alkaline phosphatase in plasma by wheat-germ lectin methods in bone disease.

Bone-origin ALP in plasma may be readily quantified by WG-lectin methods and such measurements (reflecting osteoblastic activity) are useful in a wide variety of bone disorders. The studies summarized here have confirmed that ALP isoenzyme examination by these methods adds tissue specificity and diagnostic sensitivity to total ALP measurement.

Liver function profiles and their interpretation.

Plasma bilirubin, protein and enzyme measurements are used to evaluate hepatocellular function and integrity and bile duct patency. This 'liver function test' package is of value for the detection, confirmation, categorization and assessment of liver disease.

Renal isoamylase clearance as a measure of altered renal charge selectivity in patients with diabetes mellitus.

Microalbuminuria is well established as a marker for early renal damage in diabetic patients. Differences in charge selectivity in glomerular protein filtration may also be an early marker of renal damage. We investigated the possible usefulness of the renal clearances of pancreatic and salivary amylases, and the ratio of the two, as markers of early renal damage in 55 diabetic subjects and 21 healthy controls.

Benign familial hyperphosphatasaemia as a cause of unexplained increase in plasma alkaline phosphatase activity.

Aims: To consider a possible genetic origin for the persistent unexplained increase in plasma alkaline phosphatase (ALP) in five non-related patients referred over an 18 month period.

Methods: Plasma ALP isoenzyme activities were measured in patients and their first degree relatives.

Results: In each patient there was a noticeable increase in intestinal plasma ALP, either alone or accompanied by an increase in bone or liver ALP.

Multicenter evaluation of Iso-ALP test kit for measurement of bone alkaline phosphatase activity in serum and plasma.

A test kit (Iso-ALP, Boehringer Mannheim) for measuring human bone alkaline phosphatase activity in serum or plasma was evaluated in five laboratories in three countries. The assay is based on the principle described by Rosalki and Foo (Clin Chem 1984;30:1182-6) and uses wheat germ lectin to precipitate bone alkaline phosphatase. Residual ALP in the supernate in comparison with total ALP is used to quantify the bone fraction.

Bone-derived serum enzymes and bone density in perimenopausal Caucasian women.

Serum levels of bone-origin alkaline phosphatase and of tartrate-resistant acid phosphatase were measured in Caucasian women aged 41-69 years who had volunteered for bone densitometry. Bone alkaline phosphatase and tartrate-resistant acid phosphatase were inversely correlated with vertebral bone density and with femoral neck bone density. Bone alkaline phosphatase and acid phosphatase were also significantly correlated, consistent with the concept of 'coupling' between osteoblast and osteoclast activity.