Development and validation of a fast and automated DNA identification line.

The importance of DNA evidence for gaining investigative leads demands a fast workflow for forensic DNA profiling performed in large volumes. Therefore, we developed software solutions for automated DNA profile analysis, contamination check, major donor inference, DNA database (DDB) comparison and reporting of the conclusions. This represents the Fast DNA IDentification Line (FIDL) and this study describes its development, validation and implementation in criminal casework at the authors' institute.

Local structure and oxide-ion conduction mechanism in apatite-type lanthanum silicates.

The local structure of apatite-type lanthanum silicates of general formula La(SiO)O has been investigated by combining the atomic pair distribution function (PDF) method, conventional X-ray and neutron powder diffraction (NPD) data and density functional theory (DFT) calculations. DFT was used to build structure models with stable positions of excess oxide ions within the conduction channel. Two stable interstitial positions were obtained in accordance with literature, the first one located at the very periphery of the conduction channel, neighbouring the SiO tetrahedral units, and the second one closer to the channel axis.

Quality of life in patients with primary hypothyroidism related to BMI.

Objective: Many patients treated for primary hypothyroidism have an unexplained reduced quality of life (QOL). We studied the relation between QOL and various parameters in treated hypothyroid patients.

Design And Methods: QOL analysis was done in 90 consecutive patients (77.

Atomistic simulations of TeO₂-based glasses: interatomic potentials and molecular dynamics.

In this work we present for the first time empirical interatomic potentials that are able to reproduce TeO2-based systems. Using these potentials in classical molecular dynamics simulations, we obtained first results for the pure TeO2 glass structure model. The calculated pair distribution function is in good agreement with the experimental one, which indicates a realistic glass structure model.

[Ethnic differences in laboratory results].

Over the years the Netherlands has become a country with a population comprising over 20% of immigrants. Immigrants differ from natives in both biological and cultural aspects, amongst others in laboratory results, but also in level of participation in clinical trials, and treatment outcomes. It is important for physicians to keep these differences between ethnic groups in mind.

Population pharmacokinetic and pharmacodynamic model-based comparability assessment of a recombinant human Epoetin Alfa and the Biosimilar HX575.

The aim of this study was to develop an integrated pharmacokinetic and pharmacodynamic (PK/PD) model and assess the comparability between epoetin alfa HEXAL/Binocrit (HX575) and a comparator epoetin alfa by a model-based approach. PK/PD data-including serum drug concentrations, reticulocyte counts, red blood cells, and hemoglobin levels-were obtained from 2 clinical studies. In sum, 149 healthy men received multiple intravenous or subcutaneous doses of HX575 (100 IU/kg) and the comparator 3 times a week for 4 weeks.

Clinical programs in the development of similar biotherapeutic products: rationale and general principles.

Similar biotherapeutic products (SBPs) or biosimilars are biologics developed by pharmaceutical manufacturers to match originator biologics that have been on the market for a long time and lost their exclusivity (patent and market protection). The recently issued WHO guidelines on evaluation of SBPs provide clear guidance for manufacturers and regulators on how to develop and gain approval for these products. The present contribution illustrates the rationale for and general principles of the clinical programs used in the development of SBPs, taking the example of the three biosimilar products developed and marketed in Europe by Sandoz, namely growth hormone (Omnitrope®, the first ever EU biosimilar approval), erythropoietin α (Binocrit®), and filgrastim (Zarzio®).

The activation of monocyte and T cell networks in patients with bipolar disorder.

Objectives: We recently described a monocyte pro-inflammatory state in patients with bipolar disorder (BD). We hypothesized that the CD4(+)T cell system is also activated and determined percentages of Th1, Th2, Th17 and CD4(+)CD25(high)FoxP3(+) regulatory T cells.

Methods: We carried out a detailed FACS analysis to determine the various T cell subsets and used frozen stored peripheral blood mononuclear cells (PBMC) of 38 BD patients (of whom we previously had tested monocytes for pro-inflammatory gene expression (Drexhage et al.

Effects of evening vs morning levothyroxine intake: a randomized double-blind crossover trial.

Background: Levothyroxine sodium is widely prescribed to treat primary hypothyroidism. There is consensus that levothyroxine should be taken in the morning on an empty stomach. A pilot study showed that levothyroxine intake at bedtime significantly decreased thyrotropin levels and increased free thyroxine and total triiodothyronine levels.

Population modeling of filgrastim PK-PD in healthy adults following intravenous and subcutaneous administrations.

Filgrastim is a recombinant human granulocyte colony stimulating factor (G-CSF) that stimulates production of neutrophils. The objective of this analysis was to develop a pharmacokinetic (PK) and pharmacodynamic (PD) model to account for an increase in G-CSF clearance on multiple dosing because of an increase of the G-CSF receptor-mediated endocytosis. Data from 4 randomized studies involving healthy volunteers were used for analysis.

Bioequivalence between novel ready-to-use liquid formulations of the recombinant human GH Omnitrope and the original lyophilized formulations for reconstitution of Omnitrope and Genotropin.

Objective: Two strengths of a novel ready-to-use liquid preparation of the recombinant human GH (rhGH) Omnitrope were developed to increase the convenience for the patients.

Design: Omnitrope 3.3 mg/ml solution or Omnitrope 6.

An inflammatory gene-expression fingerprint in monocytes of autoimmune thyroid disease patients.

Context: In monocytes of patients with autoimmune diabetes, we recently identified a gene expression fingerprint of two partly overlapping gene clusters, a PDE4B-associated cluster (consisting of 12 core proinflammatory cytokine/compound genes), a FABP5-associated cluster (three core genes), and a set of nine overlapping chemotaxis, adhesion, and cell assembly genes correlating to both PDE4B and FABP5.

Objective: Our objective was to study whether a similar monocyte inflammatory fingerprint as found in autoimmune diabetes is present in autoimmune thyroid disease (AITD).

Design And Patients: Quantitative PCR was used for analysis of 28 genes in monocytes of 67 AITD patients and 70 healthy controls.

Seven years of safety and efficacy of the recombinant human growth hormone Omnitrope in the treatment of growth hormone deficient children: results of a phase III study.

Aim: This phase III clinical study in growth hormone deficiency (GHD) children with growth retardation was designed to compare efficacy and safety of Omnitrope((R)) with Genotropin((R)) and assess the long-term safety and efficacy of Omnitrope((R)). The results of 7 years of treatment with Omnitrope((R)) are presented.

Patients And Methods: Eighty-nine treatment-naïve, prepubertal children with GHD were randomized (part 1) to Omnitrope((R)) lyophilisate (group A, n = 44) or Genotropin((R)) (group B, n = 45) for 9 months and received a subcutaneous dose of 0.

Symptomatic hypoparathyroidism based on a 22q11 deletion first diagnosed in a 43-year-old woman.

Congenital hypoparathyroidism usually manifests in early childhood with hypocalcaemia with or without clinical characteristics. This report describes a Caucasian woman who, at the age of 43 years, was diagnosed with dysgenesis of the parathyroid glands due to a de novo microdeletion in chromosome 22q11 or DiGeorge syndrome. This syndrome is characterised by a considerable variability in clinical symptoms, including heart defects, thymic hypoplasia and mental retardation.

Thyroid function disorders--Guidelines of the Netherlands Association of Internal Medicine.

Thyroid function disorders are common with a female to male ratio of 4 to 1. In adult women primary hypothyroidism and thyrotoxicosis have a prevalence of 3.5/1000 and 0.

[A mass in the popliteal fossa and leucocytosis caused by a paraneoplastic leukemoid reaction].

A 65-year-old woman was referred with a mass in the right popliteal fossa, fever and leucocytosis reaching 105 x 10(9)/l. Her medical history included the excision of a melanoma from the right ankle more than 20 years before. Ultrasound, CT and positron-emission tomography showed the mass in the right knee but no other lesions.

Efficacy and safety of a new ready-to-use recombinant human growth hormone solution.

We report 24-month interim results of two multicenter phase III studies in previously untreated children with growth failure secondary to GH deficiency (GHD) that were paramount to the development of a new recombinant human GH (rh- GH, somatropin), approved as the first 'biosimilar' in Europe. Study 1 consisted of 3 parts performed in 89 children. The objective was to compare efficacy and safety of the lyophilized formulation of the new somatropin [Somatropin Powder (Sandoz)] with a licensed reference rhGH preparation and the liquid formulation of the new somatropin [Somatropin Solution (Sandoz)] and to assess long-term efficacy and safety of this ready-to-use Somatropin Solution.

Effects of evening vs morning thyroxine ingestion on serum thyroid hormone profiles in hypothyroid patients.

Objective: Standard drug information resources recommend that l-thyroxine be taken half an hour before breakfast on an empty stomach, to prevent interference of its intestinal uptake by food or medication. We observed cases in which TSH levels improved markedly after changing the administration time of l-thyroxine to the late evening. We therefore conducted a pilot-study to investigate whether l-thyroxine administration at bedtime improves TSH and thyroid hormones, and whether the circadian rhythm of TSH remains intact.

Fundamental state quantities and high-pressure phase transition in beryllium chalcogenides.

In this work we study the structural and electronic properties of Be chalcogenides (BeS, BeSe and BeTe) using two different methods: the full-potential linear augmented-plane wave (FP-LAPW) and the plane-wave pseudopotential (PPsPW). The exchange-correlation effects are treated in the local-density approximation (LDA) and the generalized-gradient approximation (GGA). We have evaluated the ground-state quantities such as equilibrium volume, bulk modulus and its pressure derivative as well as the elastic constants.

No clear effect of diabetes education on glycaemic control for Turkish type 2 diabetes patients: a controlled experiment in general practice.

Background: In Turkish immigrant diabetics, problems with communication and cultural differences may hinder delivery of diabetes care.

Methods: In a prospective controlled study, the effect of an ethnic-specific diabetes education programme on glycaemic control and cardiovascular risk factors in Turkish type 2 diabetes patients was assessed, by comparing Turkish diabetics who were offered the education programme with Turkish diabetics offered routine care only (control group). From 16 general practices (31 GPs) in Rotterdam, 104 Turkish type 2 diabetes patients were recruited, 85 of whom could be assessed at one-year follow-up.