The serum selenium concentrations in children and young adults: a long-term study during the Finnish selenium fertilization programme.

OBJECTIVE: To investigate the effects of the Finnish nationwide selenium (Se) fertilization programme on the Se status of the population. DESIGN AND SUBJECTS: Serum Se concentrations from 1985-1992 from 1568 healthy children and young adults in southwestern Finland were determined using direct electrothermal atomic absorption spectrometry. RESULTS: The mean concentration in young adults increased from 1.04 micromol/L in 1985 to 1.59 micromol/L in 1990. Children younger than 15 y had lower concentrations than adults, with an increase from 0.87 micromol/L in 1985 to 1.31 micromol/L in 1990. The younger the children, the lower the Se concentrations tended to be. At the age of about seven months no significant difference was noted between breast-fed and formula-fed infants. From 1991, when the amount of Se added to fertilizers was reduced and less foreign high-Se cereal was imported, the Se concentrations decreased in all age groups. CONCLUSIONS: The nationwide Se supplementation programme has succeeded in elevating the Se intake and the serum Se concentrations in the Finnish population.

Serum selenium, zinc and copper in Swedish and Finnish orienteers. A comparative study.

Serum selenium, zinc and copper concentrations of 127 highly-trained Swedish orienteers have been analysed and compared with the corresponding values of 30 elite Finnish orienteers, and those of 111 healthy Finnish medical students. The mean serum selenium levels of Finnish orienteers, 1.35 mumol l-1, and students, 1.38 mumol l-1, were statistically significantly higher than those of Swedish orienteers, 1.09 mumol l-1. The serum levels of selenium were lower than 1.0 mumol l-1 in 27% of Swedish orienteers. This is obviously due to the lower selenium intake of the population in Sweden, where the soil selenium content is known to be low. Serum levels of zinc were within the reference interval in both Swedish and Finnish orienteers (mean values 14.8 and 14.1 mumol l-1, respectively). However, Finnish students had significantly lower serum levels of zinc, 12.5 mumol l-1. The mean serum concentration of copper was statistically significantly higher in females than in males.

Effect of nationwide selenium supplementation in Finland on selenium status in children with juvenile rheumatoid arthritis. A ten-year follow-up study.

A study was performed on the effect of increased selenium intake on the serum selenium level of 212 children with juvenile rheumatoid arthritis (JRA) and of 214 controls in a follow-up study during the Finnish nationwide selenium fertilization programme, which was started in 1984. The mean serum level of selenium increased from 0.90 mumol l-1 in 1985 to 1.56 mumol l-1 in 1990 in the children with JRA. The corresponding selenium levels in the controls were 0.87 mumol l-1 in 1985 and 1.33 mumol l-1 in 1990. Boys had slightly higher selenium levels in all the age groups among the patients and the controls. During the entire 10-year observation period, the patients with JRA had slightly higher mean levels of selenium than the controls. The age of the children did not have any significant effect on the selenium level in either group. The present study shows that the main factor affecting the serum level of selenium was the dietary intake of selenium both in patients and in healthy controls.

Environmental effects of nationwide selenium fertilization in Finland.

To study the possible pollution of natural waters by selenium added to agricultural fertilizers, water selenium concentrations were determined in lakes and ground water pools during the year 1992, when the enrichment of fertilizers by selenium had continued for 8 yr. Water samples were preconcentrated by evaporating, and selenium concentrations were analyzed fluorometrically using the dye 2,3-diaminonaphthalene after wet digestion. In lake water samples from 13 lakes, no significant correlations were found between selenium and pH, chlorophyll A, total nitrogen, or phosphorus. Agriculturally affected and nonaffected lakes had no differences in their selenium concentrations. In the lakes that were surrounded by cultivated fields mean water selenium was 83.4 ng/L (range: 75.2-93.4 ng/L, n = 9). Correspondingly, in lakes situated in forests without agricultural surroundings, mean water selenium concentration was 76.5 ng/L (range: 51.2-110 ng/L, n = 3). Only one lake in the close vicinity of a coal power plant had a high water selenium concentration (mean 272 ng/L). In ground water samples, there was a big variation in selenium levels between different pools, the levels varying between 33 and 260 ng/L. This variation may partly be explained by different selenium concentrations of the bedrock and sediments. However, simultaneous increase of total nitrogen, phosphorus, and selenium levels in consecutive samples from some ground water pools indicates leaching of selenium from the fertilizers into the ground water in certain areas.

Reliability and adequacy of discharge diagnosis databases in the production of reference values.

Discharge diagnoses provide a possibility to select patients individually and then to establish reference values for both "pathological" and control groups. Currently, the available diagnostic information is still at its infancy and should be carefully evaluated before the reference values based on those groups are utilized. It is anticipated that electronic storage of diagnostic and therapeutic information will be applied more commonly in the future as the development of computers makes it easier. The advanced utilization of laboratory data challenges physicians both in the clinical and laboratory side to participate in this development in order to make the information systems serve their actual needs more closely.

Effect of platelet count on serum and plasma potassium: evaluation using database information from two hospitals.

The availability of retrospective data from potassium (K+) analyses from two hospitals, one using serum and the other plasma for electrolyte measurements, offered us the possibility to investigate the effect of blood platelet count on serum and plasma K+ concentrations. A weak correlation between plasma K+ and platelet count was observed. The in vitro increase of serum K+ in proportion to the platelet count has clinical significance in conditions, where it may impede the detection of an underlying true K+ disorder. Nomograms and correction factors, based on the correlation between platelet count and serum K+, have been suggested also in some recent reports. In the present study unselected routine patient data was used as source data. The effect of platelet count on the concentration of K+ in serum was lower than reported in previous studies, as indicated by the regression analysis. An increase of 1000 x 10(9)/l in the blood platelet count would cause an increase of about 0.7 mmol/l in the serum K+ concentration (p < 0.0001, r = 0.155). The weak correlation between platelet count and serum K+ does not support the application of platelet-count-based correction of serum K+ level in thrombocytosis. The laboratory should notify the clinician of the significance of the in vitro increase of K+ caused by increased platelet count. K+ should be measured from plasma in such cases.

Serum selenium levels in diabetic children. A followup study during selenium-enriched agricultural fertilization in Finland.

The effect of increased selenium uptake on serum selenium in diabetic children was investigated during the first 9 yr of the Finnish nationwide selenium fertilization program, which started in 1984. Serum selenium concentrations were followed in 237 diabetic children (mean age 8.1 yr) and 214 controls from 1984 to 1992. The control group consisted of 107 siblings of the diabetics and of 107 other healthy children of corresponding age groups. Selenium was determined by direct electrothermal atomic absorption spectrophotometry. The effect of the increased uptake was seen in both diabetic and in control persons. Before the autumn of 1985, diabetic patients had significantly higher serum selenium levels than their siblings or the other healthy controls. Toward the end of year 1987, this difference had disappeared. After that, serum selenium levels continued to increase until the year 1990. In 1990 the mean selenium serum level of diabetic patients was 1.36 mumol/L and that of controls 1.33 mumol/L. The duration of diabetes did not have any effect on selenium serum levels. Slightly higher serum selenium in new diabetic patients before the start of therapy was explained by the dehydration state. The patients who were younger than 3 yr had slightly lower selenium serum levels when compared with older age groups. This difference was observed, however, only during the first 3 yr of the study. After that, when the selenium intake increased in general, no age-dependent differences were found anymore. There were no significant differences in serum selenium levels between males and females in either diabetic patients or in controls.

Reference intervals developed from data for hospitalized patients: computerized method based on combination of laboratory and diagnostic data.

We utilized the databases of a hospital information system to select for determination of reference values various individual hospitalized patients on the basis of their diagnoses at discharge. The nonparametric 2.5-97.5% "health-related" reference intervals were calculated for hemoglobin concentration, mean corpuscular volume (MCV), and erythrocyte count for both sexes. After excluding patients with diseases possibly affecting erythrocyte variables, we obtained a final group of 1786 women and 1450 men, ages 20-65 years, who were studied in age groups of 20-30, 30-45, 45-55, and 55-65 years. The upper reference limits of the MCV results obtained from hospitalized patients were higher than those produced conventionally from healthy individuals, as would be intuitively suggested by clinical experience. This method, based on selection by diagnosis, could be applicable to various analytes measured in hospital laboratories, provided sufficient data are available as databases.

Detection of Philadelphia chromosome using PCR and europium-labeled DNA probes.

More than 95% of the patients with chronic myelogenous leukemia (CML) carry translocations between protooncogene abl of chromosome 9 and bcr gene of chromosome 22, resulting in the Philadelphia chromosome (Ph1). After allogeneic bone marrow transplantation (BMT) it is important to detect possible residual malignant cells in CML patients. A new sensitive hybridization method combined with polymerase chain reaction (PCR), based on the detection of the europium (Eu3+) label by time-resolved fluorescence, was applied for the detection of Ph1 chromosome. Total RNA from 10(6) peripheral blood leukocytes was isolated by the acid guanidinium thiocyanate-phenol-chloroform extraction. After cDNA synthesis by reverse transcriptase, the PCR amplification (30 cycles) was carried out. In the detection phase two oligonucleotide probes were used in the hybridization reaction, one biotinylated (bcr gene, exon 2) and one (abl gene) labeled with Eu3+. The hybrids were collected in a streptavidin-coated microtitration well and the bound Eu3+ was measured in a time-resolved fluorometer. To assess the sensitivity of the method, different numbers of CML cell line K562 cells were mixed with 10(5) apparently normal human leukocytes. Five K562 cells/10(5) leukocytes could be detected. Six patients with CML confirmed by clinical and cytogenetic criteria were studied. Three of the patients underwent an allogeneic BTM 6-18 months before the investigation and all of them were Ph1-negative. The other three patients who were nontransplanted were positive as expected.

Generation of reference values for cardiac enzymes from hospital admission laboratory data.

An approach is described for using patient databases of a hospital information system as a source of reference values for cardiac enzymes. Of a total of 2029 emergency admission patients with serial cardiac enzyme data, 538 patients were considered "healthy" (having no damage in myocardium) because their discharge diagnoses suggested neither myocardial damage nor any other condition that could lead to elevated enzyme activities, and because their serially collected cardiac enzyme activities remained stable. Enzyme activities of creatine kinase (EC 2.7.3.2), creatine kinase isoenzyme MB, lactate dehydrogenase (EC 1.1.1.28), and lactate dehydrogenase isoenzyme 1 of these patients at admission to hospital were considered as suitable health related reference values. The upper (97.5%) reference limits of activities, measured at 37 degrees C according to Scandinavian recommendations, were as follows (age dependent limits given at 25 and at 75 years of age, U/l): creatine kinase men 268, 192; creatine kinase women 200 (no age effect); creatine kinase-MB 16, 24; lactate dehydrogenase 497, 603; lactate dehydrogenase isoenzyme 1 103, 140. For comparison, reference values were also produced conventionally from a group of 246 healthy subjects. Observed effects of age on enzyme activities were quite similar to those in the selected patient group. Calculated reference limits for isoenzymes creatine kinase-MB and lactate dehydrogenase isoenzyme 1 were also similar but reference limits for less cardiospecific total enzyme activities, creatine kinase and lactate dehydrogenase, were more variable between these two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Low zinc intake during exclusive breast-feeding does not impair growth.

We studied zinc nutrition in exclusively breast-fed infants whose growth deviated from the norm. Their number fell from 200 at birth to 116 at the age of 6 months and 36 at the age of 9 months. The mothers received 0, 20, or 40 mg Zn++ as sulfate daily. Breast milk intake and concentrations of zinc in milk as well as in maternal and infant serum were measured. Individual zinc concentrations in milk showed channeling. The 20-mg supplement had no effect on the parameters measured. In contrast, 40 mg increased the maternal serum zinc concentration by 2 months and slowed the normal decline of milk zinc concentration by 6 months. Maternal supplementation had no effect on infant serum concentrations; they remained lower than adult levels throughout the 1st year of life. Zinc intake was low (about one-tenth of RDA), but it seemed to be adequate; the serum concentrations of the infants were stable after the age of 2 months. Low zinc concentrations in serum were not associated with impaired growth. On the contrary, the infants with the highest rates of growth had the lowest zinc concentrations. The infant serum zinc concentrations were channeled, but they were also influenced by the zinc intake. Reference values for breast-fed infants are given.

Method for determining reference changes from patients' serial data: example of cardiac enzymes.

Changes between serial laboratory test results can be significant, even if none of the individual results exceeds the reference interval. We developed a statistical method for the calculation of reference change limits from routine patients' data for situations in which the majority of the patients can be considered suitable reference subjects. The method was applied to cardiac enzyme data [creatine kinase (CK; EC 2.7.3.2), creatine kinase isoenzyme MB (CK-2), lactate dehydrogenase (LD; EC 1.1.1.28), and lactate dehydrogenase isoenzyme 1 (LD-1)] from 2029 consecutive patients. We used hospital discharge diagnoses to exclude patients with the diagnosis of myocardial infarction or myocarditis, but we also studied the characteristics of the method on unselected patients' data. The reference change limits derived from the diagnosis-selected patient group were as follows (U/L, activity measurements in serum at 37 degrees C according to Scandinavian recommendations): CK from -39 to 27, CK-2 from -8 to 7, LD from -86 to 85, and LD-1 from -19 to 15. Similar limits were obtained by conventional statistical methods from a group of 29 hospitalized patients with no myocardial symptoms. Our results suggest that it is possible to produce clinically applicable reference change limits from routine data.

The effect of intermaxillary fixation on leukocyte zinc, serum trace elements and nutritional status of patients undergoing maxillofacial surgery.

Mononuclear cell (MNC), polymorphonuclear cell (PMNC) and serum zinc levels were studied in 17 oral surgical patients with intermaxillary fixation. Serum copper, iron, selenium and bromide concentrations were also measured together with common indices of nutritional status. Nine patients received nutritional counselling. Eight patients had, in addition, oral supplementation with a commercial formula. No changes in intracellular or serum zinc levels were seen during the study period. A statistically significant decrease was seen in mean body weight with subsequent changes in anthropometry. Maximal mean weight loss was 6.0 +/- 3.8% in control group and 3.8 +/- 2.7% in supplemental group. The impaired oral intake due to intermaxillary fixation does not interfere significantly with zinc status as estimated by MNC, PMNC or serum zinc levels. The reduction in body weight and anthropometric indices in the relatively short fixation period may be clinically significant in some patients. Supplementation with a commercial formula helps to maintain the nutritional status of these patients.

The effect of nationwide selenium enrichment of fertilizers on selenium status of healthy Finnish medical students living in south western Finland.

In Finland commercial fertilizers have been enriched with sodium selenate since July 1, 1984 in order to compensate for the poor selenium content of the soil. Fertilizers that are used for the production of hay and fodder were supplemented with 6 mg/kg of selenium, whereas fertilizers used for the production of cereals were supplemented with a higher dose, 16 mg/kg fertilizer. The effects of selenium fertilization were first seen in diary products in June 1985, and from the beginning of August 1985, the effect was evident also in wheat flour, beef, and bovine liver. In this study the selenium status of 108 healthy young adults has been systematically documented since November 1985, at which time the mean selenium serum level (S-Se) was 1.05 umol/L. A steady increase was observed until November 1989, when the maximum level, with a mean of S-Se 1.6 umol/L was reached. After that, a slight decrease has occurred. The mean serum selenium level in autumn 1991 in a new group of 35 students was 1.58 umol/L. This decrease can be explained by the high amount of imported cereals in 1988 and 1989, which was reflected also in the serum selenium levels. The glutathione peroxidase activity in erythrocytes in 1989-1990 was at the same level as in 1985 and 1986.

Quality control of multichannel hematology analyzers. Bivariate on-line comparison of MCV and MCH values for the detection of random errors.

Volume and hemoglobin content of red blood cells are physiologically interdependent variables but are measured independently in multichannel hematologic analyzers. Therefore correlation of these results to each other can be used as an additional step in internal quality control. To facilitate precise correlation, data were collected from 44,873 consecutive routine determinations of red blood cell parameters. Gaussian distributions were fitted to the original distributions and bivariate elliptical acceptance limits were calculated for simultaneous evaluation of mean corpuscular volume and mean corpuscular hemoglobin results. With the proposed method, rare combinations of the three directly measured red blood cell parameters (hemoglobin, red blood cell count, and mean corpuscular volume) can be identified for the detection of random analytical or preanalytical errors. This mean corpuscular volume-mean corpuscular hemoglobin rule could be added to internal quality-control programs of hematologic analyzers to improve detection of unusual results and possible random errors.

Serum trace element concentrations and iron metabolism in allogeneic bone marrow transplant recipients.

Serum trace element concentrations, parameters of iron metabolism and serum protein concentrations were investigated in thirteen adult recipients of bone-marrow transplants receiving total parenteral nutrition. Six of the patients died during the four weeks follow-up. Serum zinc concentrations were initially low but increased during the treatment. They also tended to be lower in dying patients than in survivors. Concentrations of serum copper and selenium remained unaltered. Serum iron started to increase during the preconditioning and remained raised for three weeks. No significant changes occurred in serum transferrin levels. Transferrin saturation increased during the preconditioning and started to return to normal after day +14. Serum ferritin was greatly raised from the start and increased further during the procedure. Routine trace element substitution seemed to be sufficient during total parenteral nutrition with the possible exception of zinc. A return to normal transferrin saturation after day +14 may be an early favourable sign that the graft is taking and hematopoietic recovery commencing.

The effect of postoperative radiotherapy on leukocyte zinc, serum trace elements and nutritional status of breast cancer patients.

Mononuclear (MNC) and polymorphonuclear cell (PMNC) zinc content was determined together with serum zinc, copper, selenium and iron concentrations in 24 operable breast cancer patients during and after postoperative radiotherapy. Anthropometric and biochemical indices of nutritional status were measured as background data. The measurements were carried out in the years 1987-1988. Nine patients used unconventional multivitamin or trace element preparations. A steady but statistically insignificant decrease in PMNC zinc was seen during treatment. No changes occurred in MNC zinc. Serum copper levels increased in five patients possibly due to tamoxifen treatment, but no other alterations occurred in serum trace element levels. Appetite was well maintained and nutritional status remained unaltered. Postoperative radiotherapy for breast carcinoma had thus no effect on either trace element or nutritional status. Patient-initiated alternative treatments did not significantly affect their trace element levels. This was probably due to small supplementation doses or irregular use of the preparations.

Double monoclonal time-resolved immunofluorometric assay of beta 2-microglobulin in serum.

Previously reported immunochemical assays of beta 2-microglobulin (beta 2m) have usually been based on polyclonal antisera. We have developed a "sandwich"-type time-resolved immunofluorometric assay (TR-IFMA) for beta 2m in serum, based on two monoclonal antibodies against human beta 2m. Microtiter wells are coated with the capture antibody, and the tracer antibody is labeled with a europium chelate. In a simple and fast assay procedure, prediluted serum samples are incubated with the tracer for 1 h in the microtiter wells, after which the wells are washed and the fluorescence of Eu is measured. The mean analytical recovery was 101.8% and results by TR-IFMA showed a good linear correlation with those by an established radioimmunoassay. The analytical range of TR-IFMA is large and well suited for clinical purposes.

Recommendation for collection of venous blood from children, with special reference to production reference values.

Reference values should be produced under standardized conditions. To enable comparison it is desirable to use the same procedure also in other clinical situations. A procedure for the collection of venous blood from children with special reference to production of reference values is recommended. It deals with five items: preparation of the child before specimen collection, preparation of the blood collection site, equipment for specimen collection, the specimen collection itself, and handling and storage of the specimen. Alternative methods are described since no single method is suitable for all paediatric age groups. The problem of adhering to a proposed procedure during routine clinical work is also commented upon. The recommendation has been produced as a joint effort of the Scandinavian Committee on Reference Values and a working group set up by the National Paediatric Societies in the Nordic countries.