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. Specificity for alcohol abuse ranges from 80 to 95% in the general population and from 70 to 80% in liver clinic patients.

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. Identification uses measurement of serum iron, iron-binding capacity (or transferrin) and ferritin, together with initial or confirmatory genetic DNA studies.

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. In patients with ischaemic chest pain, a raised CRP value on hospital admission is associated with an adverse prognosis. In apparently healthy individuals, a raised CRP value indicates an increased risk of developing atherosclerotic vascular disease, but also increased benefit from aspirin prophylaxis and treatment of hyperlipidaemia.

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. Serial measurements are also of value for monitoring treatment of prostate cancer and for post-treatment surveillance.

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. With the exception of measurement of the bone enzymes, bone-specific alkaline phosphatase and tartrate-resistant acid phosphatase, bone marker measurements require complex and expensive immunoassays. As a general rule, the simple enzyme measurements can precede other investigation in most bone disorder> Bone-specific alkaline phosphatase measurement alone is generally adequate for the investigation of osteomalacia, Paget's disease and hyperparathyroidism but should be combined with measurement of tartrate-resistant acid phosphatase in suspected metastatic disease, and in multiple myeloma. Determination of both enzymes together may also be of value in the investigation of osteoporosis but in this disorder added benefit may be obtained by the addition of other bone markers, particularly urine deoxypyridinoline and possibly serum collagen telopeptide.

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.

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.

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 (8.2-90.3) years]. cTnT was measured by two methods: ELISA and Enzymun (Boehringer Mannheim UK, Lewes, UK), both with a detection limit of 0.05 microgram/L in 179 and 78 patients, respectively. cTnI was measured in 80 patients by the OPUS plus and OPUS Magnum systems (Dade-Behring, Milton Keynes, UK) with a detection limit of 0.5 microgram/L. Patients were classified as having chronic renal impairment (CRI), chronic renal failure (CRF), acute renal failure including those with multiple organ failure on renal replacement therapy (ARF), and patients with chronic renal failure treated with haemodialysis (HD). Cardiac troponins were detectable in the serum of patients with renal dysfunction. cTnT was detectable in 113/179 (63.1%) and 33/78 (42.3%) by the ELISA and Enzymun methods respectively. cTnI was detectable in 17/80 (21.3%). cTnT (ELISA and Enzymun methods) and cTnI were detectable with increased frequency in the CRF, HD and ARF patient groups compared with the CRI group. Cardiac troponin concentrations did not correlate with serum creatine kinase (CK) activity, CK-MB, or urea or creatinine levels. Serial cardiac troponin measurements may be required to confirm or exclude a diagnosis of acute coronary syndromes in patients with renal dysfunction.

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. 2. Twenty-four healthy male subjects were randomized to receive ethanol 0.3 g kg-1 before an evening meal on two study days and ethanol 0.3 g kg-1 after an evening meal on two study days. Plasma ethanol concentrations were measured at intervals from 0-240 min. 3. There were significant differences in the mean area under the ethanol concentration-time curve (AUC), the mean peak ethanol concentration (Cmax), the mean ethanol elimination slope and the time to peak ethanol concentration between the fed and fasted subjects. There were no significant differences between the first and second study days for either fed or fasting subjects for all parameters. 4. There was no statistically significant difference in inter- or intra-subject variance between fed and fasted studies although the coefficients of variation (standard deviation expressed as a percentage of the mean) for the differences between the first and second study day were higher for fed studies. 5. The large inter- and intra-individual variability of alcohol absorption for both fasted and fed subjects must be considered in the design of alcohol-drug interaction studies.

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. Diabetic patients with established albuminuria and microalbuminuria had increased clearance of salivary amylase and a trend toward lower pancreatic/salivary amylase clearance ratios compared to healthy controls and diabetic subjects without albuminuria, but the overlap with controls and diabetics without albuminuria was too large for the test to be useful.