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Despite considerable progress in unravelling the genetic basis of dyslipidemias, most findings are based on families with extreme phenotypes. We studied lipid levels in an extended pedigree ascertained irrespective of phenotype from the population of a recent genetic isolate in the Netherlands. Heritabilities of plasma lipid measures were examined; this analysis also included estimates of the proportion of variance attributable to ApoE genotype. The association between inbreeding and lipids was also considered, as a substantial fraction of the population had known inbreeding. A total of 868 individuals from this pedigree, containing more than 60,000 people over 15 generations, were investigated in this study. Laboratory analysis of these subjects included the determination of fasting plasma lipids. ApoE epsilon2/3/4 status was ascertained using TaqMan assays. Heritabilities for plasma lipids were estimated with adjustments for multiple covariates using SOLAR. Heritabilities for total cholesterol (TC), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), triglycerides (TG), TC/HDL ratio, and TG/HDL ratio were found to be 0.35, 0.56, 0.30, 0.24, 0.49, and 0.39, respectively. The addition of ApoE genotype in the model significantly decreased these estimates (Deltah(2) = -0.030, -0.004, -0.054, and -0.006 for TC, HDL, LDL, and TG). In a further analysis, TC and LDL were positively associated with the extent of inbreeding (p (trend) = 0.02 and p (trend) = 0.05, respectively). These data provide estimates of lipid heritability unbiased due to selection and suggest that this population represents a good opportunity to localize novel genes influencing plasma lipid levels.

Unlabelled: The purpose of the present study was to assess the effect of two types of evacuated blood collection tube on the prothrombin time and international sensitivity index (ISI) of Recombiplastin, a recombinant human thromboplastin. Vacutainer tubes were compared with Venoject II tubes. Magnesium contamination was detected in the sodium citrate solutions contained in the Vacutainer tubes with concentrations ranging from 1.1 to 1.5 mmol/l. In contrast, magnesium ions could not be detected in the Venoject II tubes. The prothrombin ratio was decreased by contamination with magnesium ions and, hence, the ISI was increased. The magnitude of the effect of magnesium contamination on the ISI was influenced by the type of coagulometer and increased in the order: ACL Advance (3%), ACL-300 (4%), Electra-1000 (6%). The ISI bias is transmitted to the international normalized ratio (INR). In the case of the Electra-1000, the INR bias would be approximately 6% at INR 3.0 if the two types of blood collection tubes would be used without distinction. In a secondary study, the effect of magnesium contamination on the prothrombin time was assessed with the current World Health Organization international reference preparation for recombinant human thromboplastin (rTF/95). Magnesium chloride added to patients' blood (0.2 mmol/l) induced 2.3% reduction of the INR determined with rTF/95 and the manual technique., Conclusion: The magnitude of the influence of blood collection tubes contaminated with magnesium on ISI and INR determined with recombinant human thromboplastin depends on the coagulometer.

Hereditary hemochromatosis (HH) is a very common disorder characterized by iron overload and multi-organ damage. Several genes involved in iron metabolism have been implicated in the pathology of HH (refs. 1-4). We report that a mutation in the gene encoding Solute Carrier family 11, member A3 (SLC11A3), also known as ferroportin, is associated with autosomal dominant hemochromatosis.

The Hemalog system is an automated hematological instrument. From one sample this instrument determines the value for platelets (PBC), white blood cells (WBC), red blood cells (RBC), hemoglobin (Hb) and the hematocrit simultaneously. Moreover the system calculates the derived values: the mean cell volume (MCV), mean cell hemoglobin (MCH) and the mean cell hemoglobin concentration (MCHC). The values were investigated for cross sample contamination, coincidence, reproducibility, and compared with other methods. From this comparative study we can conclude that the Hemalog is a suitable and reliable instrument for hematological determination.

As recommended by the World Health Organization, standardization of prothrombin time assays involves conversion of prothrombin times into International Normalized Ratios (INR). We investigated the effect of two different methods (Nycomed's Thrombotest, and Instrumentation Laboratory's PT-fibrinogen) and three coagulation instruments (Schnitger & Gross, KC-10, and ACL) on calculations of INR. The INR plots showed considerable scatter of individual values around the regression lines when the two different methods were compared. Systematic differences in the outcome of INR calculation were related to the use of the different coagulation instruments. Prothrombin times obtained with the different instruments were linearly correlated. We used the bias of these lines to correct results for both the patients' samples and the reference samples. This correction yielded INR values from the different instruments that agreed well.

In the routine laboratory for hematology conflicting results may be obtained for the red blood cell parameters with the Coulter Counter Model S. These parameters2) are: mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC). When the values of the MCHC are above 36 g/dl something must be wrong with the blood sample of the patient. One of the reasons can be agglutination e.g. by cold agglutinins. The blood sample should be reanalysed before and after heating for 1 hour at 37 degrees C. If the values change: cold agglutinins are present; if no change occurs paraproteins, or other disturbing factors, such as bilirubin or high leucocyte levels, will be found. MCH values may also be high in some cases e.g. if the red blood cells are coated with antibodies (Coombs test positive) or after ingestion of medicines like Azathioprine. These examples show that it is possible in some cases to correlate immunological findings with the red blood cell parameters. In addition to the results with the Coulter Counter Model S, some observations on the Hemalog (Technicon) are also presented.

Reference values for hematologic parameters are determined using data from patient populations of a whole year. As a consequence, the authors are not dependent on a limited selected population and can determine reference values for all age and sex groups. It turns out that from the possible compilation technics the gamma distribution gives the best fit. If the results are compared with values stated in the literature, it is remarkable that the total number of leukocytes for men older than 50 years is higher than for women; both the absolute and relative amount of monocytes and eosinophilic granulocytes are higher for men than for women. The platelets are lower for men than for women from the age of 15 years on.

The results of the analyses which were obtained with the Hemalog for the determination of platelets, white blood cells, red blood cells, hemoglobin and hematocrit were statistically analysed for the quality control of the determinations. Now that the testing method has been applied for 6 months, it appears from the results that it is extremely suitable for the determination of hemoglobin, red blood cells and the hematocrit and, to a lesser extent, for white blood cells and platelets.