Age-Specific Reference Intervals for Thyroid-Stimulating Hormones and Free Thyroxine to Optimize Diagnosis of Thyroid Disease.

Thyroid-stimulating hormone (TSH) and subsequent free thyroxine (FT4) concentrations outside the reference interval (RI) are used to diagnose thyroid diseases. Most laboratories do not provide age-specific RIs for TSH and FT4 beyond childhood, although TSH concentrations vary with age. Therefore, we aimed to establish TSH and FT4 age-specific RIs throughout life and aimed to determine whether using these RIs would result in reclassification of thyroid disease diagnoses in adults.

Should we depend on reference intervals from manufacturer package inserts? Comparing TSH and FT4 reference intervals from four manufacturers with results from modern indirect methods and the direct method.

Objectives: Correct interpretation of thyroid function tests relies on correct reference intervals (RIs) for thyroid-stimulating hormone (TSH) and free thyroxine (FT4). ISO15189 mandates periodic verification of RIs, but laboratories struggle with cost-effective approaches. We investigated whether indirect methods (utilizing historical laboratory data) could replace the direct approach (utilizing healthy reference individuals) and compared results with manufacturer-provided RIs for TSH and FT4.

Lipid profile and NT-proBNP changes from pre-clinical to established rheumatoid arthritis: A 12 years follow-up explorative study.

Objectives: The aim of the current study was to explore the changes in lipid and NT-proBNP levels in rheumatoid arthritis (RA) patients through different phases of the disease: from the pre-clinical stage and RA onset up to the treatment phase with biological disease-modifying anti-rheumatic drugs (bDMARDS).

Methods: Thirty-eight consecutive patients, initially with arthralgia and rheumatoid factor and/or anti-citrullinated protein antibodies without arthritis, who later developed RA and eventually started treatment with bDMARDs, were included. Lipid spectrum and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were measured longitudinally from several months before diagnosis through treatment with bDMARDs.

IGF-1 is not related to long-term outcome in hyperglycemic acute coronary syndrome patients.

Purpose: Insulin-like growth factor-1 (IGF-1) has been associated with both protective and detrimental effects on the development of ischemic heart disease. The relationship between IGF-1 levels and major adverse cardiovascular events (MACE) in acute coronary syndrome (ACS) patients remains unclear. This study aimed to investigate the relationship between IGF-1 admission levels in hyperglycemic ACS patients and: (1) MACE over a 5 years follow-up, (2) type 2 diabetes at discharge, and (3) post-ACS myocardial infarct size and dysfunction.

Vitamin D and metabolic disturbances in polycystic ovary syndrome (PCOS): A cross-sectional study.

Objective: To compare vitamin D status in women with PCOS versus fertile women and subsequently evaluate the association between vitamin D status and metabolic disturbances in PCOS women.

Methods: We conducted a cross-sectional comparison study of 639 women with PCOS and 449 fertile women. Serum 25-hydroxyvitamin D (25(OH)D) was stratified into a severe deficient (< 25 nmol/l), insufficient (25-50 nmol/l), moderate (50-75 nmol/l) and adequate (> 75 nmol/l) status.

Standardization of automated 25-hydroxyvitamin D assays: How successful is it?

Objectives: Multiple 25(OH)D assays have recently been aligned to improve comparibility. In this study we investigated the performance of these assays using both native single-donor sera with target values certified by a reference method as well as single donor sera from a heterogeneous patient population.

Design & Methods: 25(OH)D levels were measured in twenty reference samples (Ref!25OHD; Labquality, Finland) using five automated methods (Lumipulse, Liaison, Cobas, iSYS and Access) and one aligned ID-XLC-MS/MS method (slope: 1,00; intercept: 0,00; R=0,996).

Effect of Vitamin D Supplementation on Glycemic Control in Patients With Type 2 Diabetes (SUNNY Trial): A Randomized Placebo-Controlled Trial.

Objective: Low vitamin D status has been associated with impaired glycemic control in patients with type 2 diabetes. The purpose of our study was to evaluate the effect of vitamin D supplementation on glycemic control in patients with type 2 diabetes.

Research Design And Methods: This randomized, double-blind, placebo-controlled trial was conducted in 275 adult patients with type 2 diabetes without insulin treatment.

Study protocol: a randomised placebo-controlled clinical trial to study the effect of vitamin D supplementation on glycaemic control in type 2 Diabetes Mellitus SUNNY trial.

Background: Besides the classical role of vitamin D on calcium and bone homeostasis, vitamin D deficiency has recently been identified as a contributing factor in the onset of insulin resistance in type 2 diabetes mellitus. However, it is uncertain whether vitamin D deficiency and poor glycaemic control are causally interrelated or that they constitute two independent features of type 2 diabetes mellitus. There are limited clinical trials carried out which measured the effect of vitamin D supplementation on glycaemic control.

Thyroid hormones and erythrocyte indices in a cohort of euthyroid older subjects.

Objectives: Hypothyroidism is associated with normocytic anaemia. Indeed, a limited number of studies have shown significant associations between free thyroxin (T4) and erythrocyte indices. These studies did not include vitamin B12, folic acid, iron and renal function in the analyses.

A patient with a prolonged activated partial thromboplastin time and a deep intracerebral haemorrhage.

We report on a 57-year-old woman with a pontine haemorrhage and an extremely prolonged activated partial thromboplastin time (aPTT) of more than 240 s, suggestive of a coagulation disorder. Given the location of the haemorrhage, which is associated with a high mortality rate, recombinant factor VIIa was administered, although not all necessary laboratory analyses could be performed at that time. In our case, a deficiency of factor XII was found, which is not associated with an increased bleeding risk.

Evaluation of a new procalcitonin assay for the Siemens ADVIA Centaur with the established method on the B.R.A.H.M.S Kryptor.

Background: In this study, we compared the B.R.A.

Sensitivity and specificity of the high fluorescent lymphocyte count-gate on the Sysmex XE-5000 hematology analyzer for detection of peripheral plasma cells.

Background: Plasma cells are one of the end products of the B-lymphocyte mediated immune response. These cells normally reside in the bone marrow or some peripheral lymphoid tissues. Increased numbers of plasma cells in the blood, usually indicates pathology such as infection, auto-immunity or haematological malignancy.

Analyses of CD27++ plasma cells in peripheral blood from patients with bacterial infections and patients with serum antinuclear antibodies.

The number of CD27++ plasma cells (PCs) in peripheral blood may be a valuable biomarker for systemic lupus erythematosus (SLE) disease management. More insights into the behavior of the PC population are, however, required to validate CD27 as a reliable biomarker. In the current study, we have monitored the PC compartment of patients with acute bacterial infections and patients with SLE and, in addition, examined the relationship between the presence of serum antinuclear antibodies (ANAs) and the number of peripheral PCs.

Detection of shortened activated partial thromboplastin times: an evaluation of different commercial reagents.

Introduction: Abnormally shortened activated partial thromboplastin times (aPTT) are associated with significantly increased risk of thrombotic disorders and in-hospital mortality. Shortened aPTTs have been related to increased levels of factor (F) VIII and thrombin-antithrombin complex (TAT). In the current study, four different commercial aPTT reagents were evaluated for their performance to detect shortened aPTTs.

Clinical laboratory findings associated with in-hospital mortality.

The diagnostic approach and the clinical management of critically ill patients is challenging. The recognition of biomarkers related to in-hospital mortality is of importance for identification of patients at increased risk of death. Many prediction models assessing the severity of illness and likelihood of hospital survival were developed using logistic regression analyses.

Subjects with a shortened activated partial thromboplastin time show increased in-hospital mortality associated with elevated D-dimer, C-reactive protein and glucose levels.

Background: Shortened activated partial thromboplastin time (aPTT) values are associated with enhanced coagulation activation. However, the clinical relevance of shortened aPTTs is not well defined. The aim of this study was to determine the in-hospital mortality rate in subjects with shortened aPTTs and the effects of polymorphism in plasminogen activator inhibitor (PAI)-, t-PA- and factor XIII gene on the coagulation status.

Abnormally short activated partial thromboplastin times are related to elevated plasma levels of TAT, F1+2, D-dimer and FVIII:C.

Abnormally short activated partial thromboplastin times (APTTs) are associated with an increased risk of thrombotic disorders. We have examined the status of coagulation activity in subjects with short APTTs. In addition, the presence of the thrombotic risk factors G1691A-factor V, G20210A-prothrombin gene mutation and factor VIII coagulant activity (FVIII:C) was determined.

Repertoire selection by pre-B-cell receptors and B-cell receptors, and genetic control of B-cell development from immature to mature B cells.

During B-cell development the surrogate light (SL) chain is selectively expressed in progenitor and precursor B cells during the developmental stages of D(H) to J(H) and V(H) to D(H)J(H) rearrangements. Approximately half of all muH chains produced by these rearrangements cannot pair with SL chains and cannot form a pre-B-cell receptor (pre-BCR). A spectrum of affinities between VpreB and individual V(H) domains generates preB cells with pre-BCR of different fitness which, in turn, determines the extent of the pre-B II-cell proliferation and the fidelity of allelic exclusion of the H chain locus.

Identification of CD19(-)B220(+)c-Kit(+)Flt3/Flk-2(+)cells as early B lymphoid precursors before pre-B-I cells in juvenile mouse bone marrow.

The combined analysis of the expression of receptor tyrosine kinases c-Kit and Flt3/Flk-2 and of the human CD25 gene expressed as a transgene under the regulation of the mouse lambda5 promoter in the bone marrow of 1-week-old mice allows us to identify three stages of B lymphocyte development before the CD19(+)c-Kit(+) pre-B-I cells. Single-cell PCR analysis of the rearrangement status of the Ig heavy chain alleles allows us to order these early stages of B cell development as follows: (i) B220(+)CD19(-)c-Kit(lo)Flt3/Flk-2(hi)lambda5(-), (ii) B220(+)CD19(-)c-Kit(lo)Flt3/Flk-2(hi)lambda5(+) and (iii) B220(+)CD19(+)c-Kit(lo)Flt3/Flk-2(lo)lambda5(+) before B220(+)CD19(+)c-Kit(lo)Flt3/Flk-2(-)lambda5(+) pre-B-I cells. All these progenitors are clonable on stromal cells in the presence of IL-7 and can differentiate to CD19(+)c-Kit(-) B-lineage cells.

Frequencies of multiple IgL chain gene rearrangements in single normal or kappaL chain-deficient B lineage cells.

PCR analyses of the kappaL chain locus in single B-lineage cells of wild-type, Ckappa-, or JCkappa-deficient homozygous or heterozygous mice often detect multiple in- and out-of-frame rearrangements at the kappaL and lambdaL loci. They are most frequent in small pre-BII cells and equally so in wild-type and kappaL chain-deficient cells. Hence, kappaL chain production appears not to inhibit secondary rearrangements.

Four of five RAG-expressing JCkappa-/- small pre-BII cells have no L chain gene rearrangements: detection by high-efficiency single cell PCR.

Single cell PCR assays have been further developed that detect over 80% of all VkappaJkappa, VkappaRS, and VlambdaJlambda rearrangements at efficiencies between 70% and 90%. These IgL chain gene rearrangement assays were used with small pre-BII cells that develop in comparably high numbers in the bone marrow of wild-type, Ckappa-deficient, and JCkappa-deficient homozygous and heterozygous mice. In all of these mice, only 15%-25% of all small pre-BII cells carry VlambdaJlambda rearrangements.