Training of pathologists in countries belonging to the European Economic Community.

The regulations and procedures for the training and assessment of pathologists engaged in morbid anatomy and histology, medical microbiology, haematology, and clinical chemistry in the countries of the European Economic Community are reviewed. Differences in the terminology used in the description of pathological disciplines are noted. Suggestions are made by which harmonisation of training, which is an EEC objective, could be achieved.

Spectroscopy, colorimetry, and biological chemistry in the nineteenth century.

The development of colorimetry and spectroscopy in the nineteenth century is described. An account is given of the application of their techniques to biological chemistry during that period.

Computer-assisted method for compiling a blood group register.

The compilation of the records of a serology department using a computer to produce alphabetically ordered files is described. This has proved to be an efficient and economical technique which may well be applied to other similar problems in a large clinical laboratory.

Quantitative measurement of faecal blood loss: comparison of radioisotopic and chemical analyses.

Blood loss in faeces was assessed by three different methods in five patients with recurrent iron deficiency. In short term (12 day) studies chemical analysis of complete stool collections for haemderived porphyrins (HemoQuant) gave results closely correlated with those obtained by measuring stool loss of 51Cr-labelled red blood cells. Whole body counting for 59Fe was relatively insensitive to small blood losses but allowed losses to be followed up over longer periods. Chemical analysis of faecal porphyrins thus provides a satisfactory alternative to radioisotopic techniques in short term quantitation of faecal blood loss, while longer term whole body counting of 59Fe may still be appropriate in a few patients for the detection and quantification of intermittent blood losses.

Serum albumin and the specificity of free tri-iodothyronine as a test for hypothyroidism.

Serum free tri-iodothyronine (FT3), using two different radioimmunoassays, and serum albumin, using bromocresol green dye-binding method, were measured prospectively in 1374 adults investigated for thyroid disease. The results of similar pairs of measurements in 6608 serum specimens obtained from adults, but using one of the radioimmunoassays for FT3, were examined retrospectively. A close correlation was observed between the FT3 values and serum albumin concentration. Normalisation of the FT3 level using a standard albumin value of 43 g/L in the absence of chemical evidence of hypothyroidism (serum thyrotrophin less than 6.5 mIU/L) gave a distribution of FT3 values which closely resembled that from a normal population. The effects of acute illness and old age, which may lower the FT3 value, can be corrected by this transformation.

The adjusted serum calcium concept--a reappraisal.

The relationship between serum calcium and albumin was studied using a data base containing biochemical results on approximately 687,000 samples. To exclude patients with established bone, liver and kidney disease, calcium and albumin values had to be accompanied by additional results falling within the laboratory reference range for urea, phosphate, globulin, alkaline phosphatase and aspartate transaminase activities. The regression coefficients of calcium on albumin changed significantly following a change of instrumentation, even though the analytical principles of the methods remained the same. In addition, using standard laboratory methods, the relationship between calcium and albumin deviated from linearity at albumin concentrations less than 30 g/L. Care is needed in the selection and clinical application of factors for the adjustment of serum calcium for changes in the concentration of circulating albumin. Using a large data base, an albumin-related reference range for serum calcium may be calculated, eliminating the need for adjusting calcium values.

Is intact PTH a sensitive biochemical indicator of deranged calcium homeostasis in vitamin D deficiency?

Intact PTH was elevated in 38/40 Asians with reduced serum 25 hydroxyvitamin D [25(OH)D] including seven patients with normal serum calcium, phosphate and alkaline phosphatase. Changes in intact PTH were disproportionately greater than for other biochemical parameters, making it the most sensitive early indicator of deranged calcium homeostasis in vitamin D deficiency.

Megaloblastic anaemia in a vegetarian Hindu community.

138 Indian patients with megaloblastic haemopoiesis were studied. All were lifelong vegetarians. The diagnosis was nutritional cobalamin deficiency in 95 and pernicious anaemia in 20; only 4 patients had folate deficiency. A third had intestinal malabsorption, 20 had features of osteomalacia, and 87 were iron deficient. Tuberculosis was diagnosed in 17. Cobalamin deficiency may have contributed to these complications via intestinal malabsorption and impaired bacterial killing of phagocytosed bacilli by cobalamin-deficient macrophages. The frequency of pernicious anaemia was the same in Indian subjects as in Caucasians.

A five year audit of the role of parathyroid hormone assays and thallium-technetium isotope subtraction scanning in the preoperative investigation of primary hyperparathyroidism.

An audit has been performed of the value of parathyroid hormone assays and thallium-technetium isotope scanning in the pre-operative investigation of 67 hypercalcaemic patients referred for surgery over a 5 year period. Parathyroid hormone assay by region-specific technique was found to have a diagnostic sensitivity of 75% (n = 52) whilst the more recent assay for the intact molecule was 97% sensitive (n = 34). Thallium-technetium isotope scanning was only 64% sensitive overall (n = 59), due in part to the small size of adenomata now being referred for surgery. This study confirms the role of the intact parathyroid hormone assay but questions that of thallium-technetium isotope scanning in standard protocols of investigation for hypercalcaemia.

Biochemical and haematological indicators of excessive alcohol consumption.

Discriminant function analysis was used to determine the optimum combination of haematological and biochemical tests which gave the best discrimination between hospital patients with high and low alcohol intakes. We studied 265 patients with alcohol-related disease, 133 gastroenterology outpatients drinking less than 20 g of alcohol per day, and 104 patients with a variety of non-alcoholic liver disease. Values of mean cell volume (MCV), serum bilirubin, aspartate transaminase, serum alkaline phosphatase (AP) and gamma glutamyl transferase (gamma GT), serum albumin, serum globulin, and uric acid were determined in each patient. The best discrimination between the three groups of patients was provided by a combination of mean corpuscular volume, log10 gamma GT, and log10 serum alkaline phosphatase. In women, 92% of the high alcohol group, 100% of the low alcohol group, and 87% of the non-alcoholic liver disease were correctly allocated by the discriminant analysis. The corresponding figures for the men were 80%, 100%, and 71%. Thus, over 80% of patients with excessive alcohol intake were correctly allocated by the use of three simple laboratory tests.

Thiamine, riboflavin and pyridoxine deficiency in psychiatric in-patients.

One hundred and seventy-two successive admissions to a district general hospital psychiatric unit were examined. Routine psychiatric, drug and dietary histories were taken and signs of avitaminosis B specifically noted. Red cell transketolase (for thiamine deficiency), glutathione reductase (for riboflavin deficiency) and aspartate transaminase (for pyridoxine deficiency) were measured. Of the patients, 53 per cent were deficient in at least one vitamin, 12 per cent in more than one (30 per cent in thiamine, 27 per cent in riboflavin and 9 per cent in pyridoxine). Schizophrenics and alcoholics were significantly over-represent in those patients low in thiamine and in more than one vitamin. Patients with an affective disorder had low riboflavin and low pyridoxine. It is suggested that affective changes are characteristic of riboflavin and pyridoxine deficiency.

Anomalies in the assay of parathyroid hormone in normocalcaemic patients with renal stone disease.

A group of 22 normocalcaemic patients with renal stone disease were retrospectively studied using seven different immunoassays for parathyroid hormone (PTH). N-terminal immunoradiometric assays and an intact hormone immunochemiluminometric assay sometimes gave results which fell above the normal range. These results were at variance with values obtained in three region-specific radioimmunoassays and an immunoradiometric assay for the intact hormone. Since these atypical samples contained normal levels of biologically active PTH the elevated immunoassay results were not thought to relate to the normal circulating hormone but rather to interference in the immunometric assays. The interfering substance was thought to be a large molecule which could not be removed by charcoal and did not dilute out in parallel to the PTH standard curve.

Early diagnosis of acute myocardial infarction with use of a rapid immunochemical assay of creatine kinase MB isoenzyme.

In 195 patients presenting with chest pain and referred acutely for cardiological assessment, blood was taken immediately for assay of creatine kinase (CK; EC 2.7.3.2) MB isoenzyme by an immunochemical method and results [mass units of enzyme per liter of plasma (microgram/L)] were obtained within 30 min of sampling. Diagnosis of acute myocardial infarction in the patients was made independently, based on electrocardiograms and conventional cardiac enzyme profiles. The administration of any thrombolytic therapy in response to the CK-MB concentration result was also noted, allowing assessment of the assay's potential influence on patient management in addition to the diagnostic efficiency evaluation. The study demonstrated that, when blood samples were collected on admission to hospital and the decision level suggested by the manufacturers was utilized, the assay had an immediate sensitivity of 52% and a specificity of 97%. Of the 81 patients who were shown by conventional means to have had acute myocardial infarction, 8 (10%) had equivocal electrocardiograms but positive CK-MB concentration results. In four of these patients (5%), thrombolytic therapy was given on the basis of the clinical features and a positive CK-MB concentration result alone.