Arginine Vasopressin Immunoreactivity is Decreased in the Hypothalamic Suprachiasmatic Nucleus of Subjects with Suprasellar Tumors

Suprasellar tumors with compression of the optic chiasm are associated with an impaired sleep–wake rhythm. We hypothesized that this reflects a disorder of the biological clock of the human brain, the suprachiasmatic nucleus (SCN), which is located just above the optic chiasm. In order to test this hypothesis, we investigated the expression of two key neuropeptides of the SCN, that is, arginine vasopressin (AVP) and vasoactive intestinal peptide (VIP), as assessed by quantitative immunocytochemistry in post‐mortem hypothalamic tissue of patients with a suprasellar tumor inducing permanent visual field defects. Post‐mortem hypothalamic tissue of 5 patients with a suprasellar tumor inducing permanent visual field defects (acromegaly n = 2, nonfunctioning macro‐adenoma n = 1, macroprolactinoma n = 1, infundibular metastasis of a colorectal adenocarcinoma n = 1) and 15 age‐ and gender‐matched controls was obtained from the Netherlands Brain Bank. Total AVP immunoreactivity in the SCN was lower in patients with a suprasellar tumor than in controls (P = 0.03). By contrast, total VIP immunoreactivity was not different between patients and controls (P = 0.44). Suprasellar tumors leading to permanent visual field defects are associated with reduced AVP, but not VIP immunoreactivity, in the SCN. These findings raise the possibility that selective impairment of the SCN contributes to sleep–wake disturbances in these patients.     

Twenty-year trends in the prevalence of Down syndrome and other trisomies in Europe: impact of maternal age and prenatal screening

This study examines trends and geographical differences in total and live birth prevalence of trisomies 21, 18 and 13 with regard to increasing maternal age and prenatal diagnosis in Europe. Twenty-one population-based EUROCAT registries covering 6.1 million births between 1990 and 2009 participated. Trisomy cases included live births, fetal deaths from 20 weeks gestational age and terminations of pregnancy for fetal anomaly. We present correction to 20 weeks gestational age (ie, correcting early terminations for the probability of fetal survival to 20 weeks) to allow for artefactual screening-related differences in total prevalence. Poisson regression was used. The proportion of births in the population to mothers aged 35+ years in the participating registries increased from 13% in 1990 to 19% in 2009. Total prevalence per 10 000 births was 22.0 (95% CI 21.7–22.4) for trisomy 21, 5.0 (95% CI 4.8–5.1) for trisomy 18 and 2.0 (95% CI 1.9–2.2) for trisomy 13; live birth prevalence was 11.2 (95% CI 10.9–11.5) for trisomy 21, 1.04 (95% CI 0.96–1.12) for trisomy 18 and 0.48 (95% CI 0.43–0.54) for trisomy 13. There was an increase in total and total corrected prevalence of all three trisomies over time, mainly explained by increasing maternal age. Live birth prevalence remained stable over time. For trisomy 21, there was a three-fold variation in live birth prevalence between countries. The rise in maternal age has led to an increase in the number of trisomy-affected pregnancies in Europe. Live birth prevalence has remained stable overall. Differences in prenatal screening and termination between countries lead to wide variation in live birth prevalence.     

Multi-modular bone healing assessment in a randomized controlled clinical trial of root-end surgery with the use of leukocyte- and platelet-rich fibrin and an occlusive membrane

Clinical Oral Investigations - The aim of this study was to assess in a multi-modular manner the bone healing 1 year post root-end surgery (RES) with leukocyte- and platelet-rich fibrin...     

Eclectic characterisation of chemically modified cell-derived matrices obtained by metabolic glycoengineering and re-assessment of commonly used methods

Azide-bearing cell-derived extracellular matrices (“clickECMs”) have emerged as a highly exciting new class of biomaterials. They conserve substantial characteristics of the natural extracellular matrix (ECM) and offer simultaneously small abiotic functional groups that enable bioorthogonal bioconjugation reactions. Despite their attractiveness, investigation of their biomolecular composition is very challenging due to the insoluble and highly complex nature of cell-derived matrices (CDMs). Yet, thorough qualitative and quantitative analysis of the overall material composition, organisation, localisation, and distribution of typical ECM-specific biomolecules is essential for consistent advancement of CDMs and the understanding of the prospective functions of the developed biomaterial. In this study, we evaluated frequently used methods for the analysis of complex CDMs. Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and (immune)histochemical staining methods in combination with several microscopic techniques were found to be highly eligible. Commercially available colorimetric protein assays turned out to deliver inaccurate information on CDMs. In contrast, we determined the nitrogen content of CDMs by elementary analysis and converted it into total protein content using conversion factors which were calculated from matching amino acid compositions. The amount of insoluble collagens was assessed based on the hydroxyproline content. The Sircol™ assay was identified as a suitable method to quantify soluble collagens while the Blyscan™ assay was found to be well-suited for the quantification of sulphated glycosaminoglycans (sGAGs). Eventually, we propose a series of suitable methods to reliably characterise the biomolecular composition of fibroblast-derived clickECM.

Common characterisation methods for cell-derived extracellular matrices (ECMs) are compared using both unmodified and azide-bearing fibroblast-derived ECM.     

Patterns of resolution of chest radiograph abnormalities in adults hospitalized with severe community-acquired pneumonia.

BACKGROUND: Timing of follow-up chest radiographs for patients with severe community-acquired pneumonia (CAP) is difficult, because little is known about the time to resolution of chest radiograph abnormalities and its correlation with clinical findings. To provide recommendations for short-term, in-hospital chest radiograph follow-up, we studied the rate of resolution of chest radiograph abnormalities in relation to clinical cure, evaluated predictors for delayed resolution, and determined the influence of deterioration of radiographic findings during follow-up on prognosis. METHODS: A total of 288 patients who were hospitalized because of severe CAP were followed up for 28 days in a prospective multicenter study. Clinical data and scores for clinical improvement at day 7 and clinical cure at day 28 were obtained. Chest radiographs were obtained at hospital admission and at days 7 and 28. Resolution and deterioration of chest radiograph findings were determined. RESULTS: At day 7, 57 (25%) of the patients had resolution of chest radiograph abnormalities, whereas 127 (56%) had clinical improvement (mean difference, 31%; 95% confidence interval, 25%-37%). At day 28, 103 (53%) of the patients had resolution of chest radiograph abnormalities, and 152 (78%) had clinical cure (mean difference, 25%; 95% confidence interval, 19%-31%). Delayed resolution of radiograph abnormalities was independently associated with multilobar disease (odds ratio, 2.87; P < or = .01); dullness to percussion at physical examination (odds ratio, 6.94; P < or = .01); high C-reactive protein level, defined as >200 mg/L (odds ratio, 4.24; P < or = .001); and high respiratory rate at admission, defined as >25 breaths/min (odds ratio, 2.42; P < or = .03). There were no significant differences in outcome at day 28 between patients with and patients without deterioration of chest radiograph findings during the follow-up period (P > .09). CONCLUSIONS: Routine short-term follow-up chest radiographs (obtained <28 days after hospital admission) of hospitalized patients with severe CAP seem to provide no additional clinical value.     

Antigen-recognition sites of micromanipulated T cells in patients with acquired aplastic anemia

OBJECTIVE: Acquired aplastic anemia (AA) is a rare disorder characterized by pancytopenia and hypocellular bone marrow. Though experimental and clinical data suggest that AA represents a T cell-mediated disease, neither the immune response nor the nature of inciting antigen(s) have been characterized so far. The identification of a restricted T cell repertoire by PCR techniques in total lymphocyte populations supports an antigen-driven T cell response. In order to investigate the clonal composition, we analyzed the gene rearrangements of the T cell receptor (TCR) variable beta chain (Vbeta) at the single-cell level. PATIENTS AND METHODS: CD3(+) T lymphocytes were micromanipulated from peripheral blood and bone marrow samples of 8 AA patients and healthy controls. Subsequently amplified VDJ gene segments of the TCRVbeta chain were analyzed for functional rearrangements. More than 500 functionally rearranged TCR loci were studied for Vbeta/Jbeta gene segment usage and molecular composition of the complementary-determining region 3 (CDR3). RESULTS: In comparison to healthy controls, the Vbeta sequences confirmed a highly restricted T cell repertoire in AA patients at the single-cell level. Both in bone marrow and peripheral blood a predominance of Vbeta13 and Jbeta2S7 was observed. Furthermore, individual clonal T-cell expansion was identified in the majority of patients. However, deduced CDR3 amino acid sequences revealed a high variability without common motifs among the 8 patients. CONCLUSION: Individual clonal T-cell expansion with high diversity of the antigen-binding sites among the analyzed patients argues for the predominance of private inciting epitopes in AA.     

Stem cell transplantation for paroxysmal nocturnal haemoglobinuria in childhood

Paroxysmal nocturnal haemoglobinuria (PNH) is a clonal haematopoietic disorder characterized by chronic or intermittent intravascular haemolysis, variable cytopenia and an increased risk of thrombosis. Stem cell transplantation (SCT) is a curative therapeutic option, but its risks must be carefully weighed against the natural course of PNH. World-wide experience with SCT for PNH in the paediatric age group is scarce. We report on two adolescents suffering from PNH with life-threatening complications who were successfully transplanted from unrelated donors. Indications and techniques of SCT in childhood PNH are discussed and an overview of the literature is given.