Jorma Järvisalo

Health-based reference intervals for ALAT, ASAT and GT in serum, measured according to the recommendations of the European Committee for Clinical Laboratory Standards (ECCLS)

The reference intervals for the activities of L-alanine aminotransferase (EC 2.6.1.2, ALAT), L-aspartate aminotransferase (EC 2.6.1.1, ASAT) and gamma-glutamyltransferase (EC 2.3.2.2, GT) in serum were determined according to the recommendations of the European Committee for Clinical Laboratory Standards (ECCLS). Serum specimens from 954 subjects were analysed for ALAT and ASAT and from 794 subjects for GT. The subjects, aged 27-67 years, were participants in general health surveys. The reference population was formed by excluding subjects with any disease, or on any medication, affecting the liver, and also those consuming excessive amounts of alcohol. The 95% inner reference intervals for ALAT and ASAT were 9-50 (n = 189) and 15-36 U l-1 (n = 192) in men and 8-38 (n = 270) and 13-33 U l-1 (n = 270) in women. For GT the reference interval was 11-58 in men (n = 165) and 8-42 U l-1 in women (n = 220). Serum GT levels correlated clearly with alcohol consumption. Serum ALAT and ASAT were only slightly associated with alcohol consumption at levels less than 280 g per week in men and 190 g per week in women. There were modest positive associations between the three enzyme levels and body mass index. None of the enzymes correlated significantly with age.

POOR APPLICABILITY OF THE FRIEDEWALD FORMULA IN THE ASSESSMENT OF SERUM LDL CHOLESTEROL FOR CLINICAL PURPOSES

OBJECTIVE To determine the accuracy of the estimation of serum low-density lipoprotein (LDL) cholesterol concentration by the Friedewald formula. METHODS Modifications of the calculation formula are presented on the basis of ultracentrifugal separation of serum high-density lipoprotein and LDL cholesterol in the specimens collected (n = 1215) in a nationwide health survey. RESULTS The formulas obtained from different subject groups differed relatively little from each other. The accuracy of the original Friedewald formula was poor; in about 36% of the subjects the error was more than 5% compared with ultracentrifugally obtained results. By applying the currently recommended coronary heart disease (CHD) risk categorizations, high proportions (5%-28%) of the subjects were classified into wrong CHD risk categories when LDL cholesterol was calculated with any of the formulas. At high serum triglyceride levels, misclassifications were especially common. CONCLUSIONS We conclude that even the most accurate LDL cholesterol calculation methods should be used with caution while classifying subjects into categories of CHD risk. In hypertriglyceridemic subjects, the calculation formulas probably should not be used at all.

Serum tumor markers CEA, CA 50, TATI, and NSE in lung cancer screening

Background. There are no effective means for screening for lung cancer, so the authors assessed the utility of four lung cancer tumor markers for screening.

Ovarian Hormone Status, Life-Style Factors, and Markers of Bone Metabolism in Women Aged 50 Years

Fifty-year-old women (n=519) attending a health examination were divided by their ovarian hormone status into four groups: premenopausal, perimenopausal, postmenopausal without ovarian hormone replacement therapy (HRT), and postmenopausal with HRT. Information on lifestyle factors was obtained with interviews and questionnaires. Bone mineral density at the calcaneus was assessed with single-photon absorptiometry, and several serum and urine markers of bone metabolism were measured. Postmenopausal women without HRT had significantly higher levels of fasting serum alkaline phosphatase, osteocalcin, total and ionized calcium, phosphate, and fasting urinary hydroxyproline than those in the three other study groups. No difference was found in bone mineral density between the premenopausal and postmenopausal groups. Postmenopausal women without HRT showed a marked correlation between serum osteocalcin and urine hydroxyproline. Both markers showed significant correlations with serum calcium, phosphate, and alkaline phosphatase. Multivariate analyses showed a statistically significant association of ovarian hormone status and body mass index with most measured markers of bone metabolism. The association between alcohol consumption and serum osteocalcin was highly significant. Cigarette smoking was associated with levels of serum alkaline phosphatase and total and ionized calcium. A weak association was found between coffee drinking and serum alkaline phosphatase.

CA 125 as a Screening Test for Ovarian Cancer

Background— Screening for ovarian cancer is based on ultrasound, colour Doppler, and tumour markers. There is only limited evidence on their discriminatory performance and no evidence on their effectiveness in reducing mortality. Objective— To investigate the discriminatory performance of CA 125 as a screening test for ovarian cancer. Methods— A registry of 15 093 serum samples drawn in 1968–72 was linked to the cancer registry. During follow up between 1968 and 1980 24 ovarian cancers were identified. One or two matched case—control design nested within the sample bank was applied and the concentrations of CA 125 were assessed. Results— Case—control differences (relative risk 4.0, 95% confidence interval 1.0 to 15.5 at 20kU/l) were found. Detection rate of the CA 125 test was 21–33% and the true negative rate was 75–98% depending on the cut off level and interval between drawing of the blood sample and diagnosis of the cancer. Conclusion— CA 125 is not a valid screening test if used alone. Case—control differences of borderline significance were found in CA 125 before diagnosis of ovarian cancer, but they were not large enough to provide a sufficient detection rate.

Health-based reference values of the Mini-Finland Health Survey: 1. Serum gamma-glutamyltransferase, aspartate aminotransferase and alkaline phosphatase

The reference values for gamma-glutamyltransferase (GT), aspartate aminotransferase (ASAT) and alkaline phosphatase (AFOS) activities in serum have been produced on the basis of measurements done in the Mini-Finland Health Survey. A representative sample of all Finns aged 30 years or over comprised 8000 persons, of whom 99.2% participated in the actual health survey. Every effort was made to obtain reference values for the healthy ambulatory population. Three separate health-derived selection criteria were used to obtain such reference values for the above-mentioned enzymes: those based on the available literature, with minor modifications, the recommendations published by the Committee on Reference Values of the Scandinavian Society for Clinical Chemistry and Clinical Physiology, criteria that were obtained after subgroup comparisons of the obtained data, where all the factors affecting the enzyme levels were identified. The recommendations of the Expert Panel on Theory of Reference Values (1987) were strictly adhered to in the statistical analyses. The distribution of the serum activity of GT was very skewed. The overall intervals for men and women were 5.1-1460 and 4.7-748 U/l, respectively. The frequency distributions could be transformed to the normal ones logarithmically. The 95% inner reference intervals for GT in the three groups were 7-76, 7-65, and 8-57 U/l for men and 6-35, 6-30 and 6-32 U/l for women, respectively. For ASAT the full intervals of the enzyme levels in serum were 2.6-770 U/l for men and 8.3-172 U/l for women. After logarithmic transformation the respective reference intervals in the three selection groups were 14-42, 14-40 and 13-39 U/l for men and 13-33, 12-31 and 13-33 U/l for women. The full intervals of AFOS were 47.5-2755 and 5.4-816 U/l for men and women, respectively; after the logarithmic transformation the reference intervals of the three selection groups were 98-267, 97-254 and 97-264 U/l for men and 77-265, 75-231 and 75-250 U/l for women, respectively.

A cancer register-based case study of occupations of patients with acute myeloid leukemia

All 636 cases of acute myeloid leukemia (AML) reported to the Finnish Cancer Registry between 1971 and 1977 inclusive were compared with patients with other forms of cancer (non‐AML) from the same registry. We found no increasing trend in the incidence of AML for either sex, but we found some evidence for regional clusters in certain provinces of Finland. A statistically significant higher incidence was found for men than women in the age group of 50 to 80 years. Classification according to occupation at the time of diagnosis revealed no statistically significant differences between the leukemia cases and the patients with other forms of cancer, but forestry work was more common among the men with AML, and both health care and food industry work were more common among the women with AML. Classification for exposure to chemicals, solvents, or drugs did not yield any statistical differences. The results were inconclusive with regard to the possible role of occupational factors in the etiology of acute myeloid leukemia.

Tumour markers and screening for gastrointestinal cancer: a follow up study in Finland

Background- Screening for gastrointestinal cancer is based mainly on a barium contrast x ray method and on identification of occult blood in stools. The methods are relatively expensive, not always acceptable to the participants, and there is only limited evidence of their effectiveness in reducing the mortality from gastrointestinal cancer. Objective - To investigate the validity of several tumour markers as a screening test for stomach cancer and for colorectal cancer. Methods- A registry of 36 265 serum samples drawn during 1968–72 was linked to the cancer registry. Follow up was during 1968–80 when 94 stomach cancers and 95 colorectal cancers were identified. One to two matched case-control design was applied, and the concentrations of CEA, CA 19–9, CA 50, and TATI were assessed. Results- The mean values of the markers between the cases and the controls were almost the same for the total material. Case-control differences were found between the 11 sets with an interval of less than one year between drawing the sample and diagnosis of the cancer. The highest validity was found in CEA for colorectal cancer (specificity 91%; sensitivity 64%) and in CA 19–9 for stomach cancer (specificity 74%; sensitivity 73%). Conclusion — CEA, CA 19–9, CA 50, or TATI are not valid screening tests. Case-control differences were found with a potential one year screening interval, but they were not large enough for sufficient validity.

Health-based reference values of the Mini-Finland Health Survey: 3. Triglycerides in total serum and in different lipoprotein fractions

The reference values for triglyceride concentrations in total serum and in its VLDL, LDL and HDL fractions have been produced based on the data obtained in the Mini-Finland Health Survey. The lipoprotein fractions were separated with ultracentrifugation. Efforts were made to obtain reference values for the healthy ambulatory population. Two health-derived selection criteria were used for inclusion of persons into the reference population: those based on the literature available and those based on the recommendations published by the Committee on Reference Values of the Scandinavian Society for Clinical Chemistry and Clinical Physiology, with minor modifications. The frequency distributions of triglycerides especially in total serum and in VLDL fraction were very skewed. Because of that the data were transformed before the calculation of the reference ranges according to the method of Box and Cox [1]. This transformation method appeared to be the best one of many tested methods in obtaining the distributions closer to the normal ones. The 95% inner reference intervals of total serum triglycerides in all subjects and in the two selection groups were 0.5-4.0, 0.5-2.8, and 0.5-3.2 mmol l-1 for men and 0.5-3.4, 0.5-2.3, and 0.5-2.4 mmol l-1 for women, respectively. The age dependence of triglyceride level was prominent in women after the early middle age. The distribution and age dependence of VLDL triglycerides resembled those of total triglycerides. In LDL and HDL fractions the skewness was not as clear as in the whole serum or in VLDL fraction.(ABSTRACT TRUNCATED AT 250 WORDS)