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Numerous studies have shown evidence supporting the benefits of universal newborn screening for primary immunodeficiencies (PID) and for Spinal Muscular Atrophy (SMA). We have developed a four-plex, real-time PCR assay to screen for Severe Combined Immune Deficiencies (SCID), X-linked agammaglobulinemia (XLA), and SMA in DNA extracted from a single 3.2 mm punch of a dried blood spot (DBS). A simple, high-throughput, semi-automated DNA extraction method was developed for a Janus liquid handler that can process 384 DBS punches in four 96-well plates in just over one hour with sample tracking capability. The PCR assay identifies the absence of exon 7 in the SMN1 gene, while simultaneously evaluating the copy number of T-cell receptor excision circles (TREC) and Kappa-deleting recombination excision circles (KREC) molecules. Additionally, the amplification of a reference gene, RPP30, was included in the assay as a quality/quantity indicator of DNA isolated from the DBS. The assay performance was demonstrated on over 3000 DNA samples isolated from punches of putative normal newborn DBS. The reliability and analytical accuracy were further evaluated using DBS controls, and contrived and confirmed positive samples. The results from this study demonstrate the potential of future molecular DBS assays, and highlight how a multiplex assay could benefit newborn screening programs.

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OBJECTIVE: The effect of exogenous hormones on the incidence of breast cancer has been extensively studied. Most studies regarding hormonal contraception have focused on combined oral contraceptives, and there is paucity of literature regarding nonoral and progestin-only contraceptives. The present study analyzed the relationship between breast cancer and use of the levonorgestrel-releasing intrauterine system. METHODS: This study was based on data gathered from a large postmarketing study on levonorgestrel-releasing intrauterine system users (n = 17,360) carried out in Finland. The results present an incidence comparison between levonorgestrel system user data and the data on average Finnish female population (derived from the Finnish Cancer Registry), between 30 and 54 years of age. RESULTS: Based on the 95% confidence intervals for the incidences of breast cancer, and the Fisher exact test, there is no indication of a difference between the levonorgestrel system users and average Finnish female population in any of the 5-year age groups. The incidence rate per 100,000 woman-years was for the age groups 30-34 years 27.2 and 25.5, for 35-39 years 74.0 and 49.2, for 40-44 years 120.3 and 122.4, for 45-49 years 203.6 and 232.5, and for 50-54 years 258.5 and 272.6, in the levonorgestrel system group and in Finnish female population, respectively. CONCLUSION: The results suggest that the use of the levonorgestrel-releasing intrauterine system is not associated with an increased risk of breast cancer.

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OBJECTIVE: The purpose of this study was to investigate the pharmacokinetics of levosimendan and to determine the primary pharmacokinetic parameters of the pharmacologically active metabolite OR-1896 in rapid and slow acetylators. METHODS: Levosimendan was administered as a constant rate (0.1 microg/(kg min)) i.v. infusion for 24h in six rapid and six slow acetylators based on N-acetyltransferase 2 genotyping. At the end of the infusion, a small amount (2.5 microg/kg) of (13)C-labeled OR-1896 was administered by i.v. infusion for 10 min. Blood samples were taken at predefined sampling points 14 days post-infusion and levosimendan and its metabolite concentrations were determined by LC-MS/MS. RESULTS: Steady-state concentrations of levosimendan were achieved within 4-8h and no differences were found in the pharmacokinetics of the parent compound between the rapid and slow acetylators. The maximum concentrations of amino phenylpyridazinone metabolite OR-1855 and N-acetylated conjugate OR-1896 were observed approximately 24h after terminating the infusion. AUC of OR-1896 was approximately 3.5 times higher in the rapid acetylators compared to the slow acetylators (P = 0.002, 95% confidence interval for group ratio from 2.0 to 8.2). The mean +/- S.D. fraction of levosimendan metabolized to OR-1896 was 6.8 +/- 2.8% in the rapid and 4.3 +/- 2.4% in the slow acetylators (P = 0.12). (13)C-OR-1855 concentrations were detected in plasma after administration of (13)C-OR-1896 indicating deacetylation from OR-1896 to OR-1855. CONCLUSIONS: Plasma OR-1896 levels during and after levosimendan treatment are dependent on the acetylation status of the subject-rapid acetylators having 3.5 times higher concentrations than slow acetylators.

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BACKGROUND: According to studies depression and depressive symptoms are more prevalent in females than in males. It is possible, however, that instruments meant to measure depressiveness are gender-biased. METHOD: This was studied by comparing two screening instruments (the Beck Depression Inventory (BDI) and the Depression Scale (DEPS) within the same population. The study sample consisted of 330 subjects taken from general population in south-western part of Finland. RESULTS: The mean BDI scores were borderline higher in females than in males, with no gender difference in DEPS scores. The difference between BDI and DEPS scores was significant between genders but not for other variables. Crying and lost interest in sex were the items on which females scored higher. CONCLUSIONS: It has been argued that these items, crying and lost interest in sex, are biologically, psychologically and culturally related to female gender and, therefore, give gender-biased results in measuring depressiveness. CLINICAL IMPLICATIONS: It is important to realise that some instruments meant for screening depression may include gender-biased items and therefore give too high scores of depressiveness in females. LIMITATIONS: The study is based on self-filled scales and its results cannot, therefore, be directly generalised to clinical depression.

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