Epileptische Enzephalopathie und Zahnschmelzdefekt (Kohlschütter-Tönz-Syndrom)

Kohlschütter-Tönz syndrome is a rare genetic disorder with neurologic symptoms – epilepsy and severe developmental delay – and defective enamel leading to yellow or brownish discoloration of teeth. The first family was described in 1974, all affected patients were male. In the meantime, families with both male and female patients were identified as well. Inheritance is thus most probably autosomal recessive; genetic heterogeneity can however not be ruled out. Clinical course and disease severity may differ even within one family. As the genetic basis has not yet been elucidated, diagnosis must be made on clinical grounds. We report three new children with Kohlschütter-Tönz syndrome in comparison to the 21 hitherto published cases.     

Hospitalizations among adults with chronic kidney disease in the United States: A cohort study

BackgroundAdults with chronic kidney disease (CKD) are hospitalized more frequently than those without CKD, but the magnitude of this excess morbidity and the factors associated with hospitalizations are not well known.Methods and findingsData from 3,939 participants enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study between 2003 and 2008 at 7 clinical centers in the United States were used to estimate primary causes of hospitalizations, hospitalization rates, and baseline participant factors associated with all-cause, cardiovascular, and non-cardiovascular hospitalizations during a median follow up of 9.6 years. Multivariable-adjusted Poisson regression was used to identify factors associated with hospitalization rates, including demographics, blood pressure, estimated glomerular filtration rate (eGFR), and proteinuria. Hospitalization rates in CRIC were compared with rates in the Nationwide Inpatient Sample (NIS) from 2012. Of the 3,939 CRIC participants, 45.1% were female, and 41.9% identified as non-Hispanic black, with a mean age of 57.7 years, and the mean eGFR is 44.9 ml/min/1.73m². CRIC participants had an unadjusted overall hospitalization rate of 35.0 per 100 person-years (PY) [95% CI: 34.3 to 35.6] and 11.1 per 100 PY [95% CI: 10.8 to 11.5] for cardiovascular-related causes. All-cause, non-cardiovascular, and cardiovascular hospitalizations were associated with older age (≥65 versus 45 to 64 years), more proteinuria (≥150 to <500 versus <150 mg/g), higher systolic blood pressure (≥140 versus 120 to <130 mmHg), diabetes (versus no diabetes), and lower eGFR (<60 versus ≥60 ml/min/1.73m²). Non-Hispanic black (versus non-Hispanic white) race/ethnicity was associated with higher risk for cardiovascular hospitalization [rate ratio (RR) 1.25, 95% CI: 1.16 to 1.35, p-value < 0.001], while risk among females was lower [RR 0.89, 95% CI: 0.83 to 0.96, p-value = 0.002]. Rates of cardiovascular hospitalizations were higher among those with ≥500 mg/g of proteinuria irrespective of eGFR. The most common causes of hospitalization were related to cardiovascular (31.8%), genitourinary (8.7%), digestive (8.3%), endocrine, nutritional or metabolic (8.3%), and respiratory (6.7%) causes. Hospitalization rates were higher in CRIC than the NIS, except for non-cardiovascular hospitalizations among individuals aged >65 years. Limitations of the study include possible misclassification by diagnostic codes, residual confounding, and potential bias from healthy volunteer effect due to its observational nature.ConclusionsIn this study, we observed that adults with CKD had a higher hospitalization rate than the general population that is hospitalized, and even moderate reductions in kidney function were associated with elevated rates of hospitalization. Causes of hospitalization were predominantly related to cardiovascular disease, but other causes contributed, particularly, genitourinary, digestive, and endocrine, nutritional, and metabolic illnesses. High levels of proteinuria were observed to have the largest association with hospitalizations across a wide range of kidney function levels.

Hsiang-Yu Chen and colleagues report the factors associated with hospitalization in patients with Chronic Kidney Disease.     

Inhibition of hormone-sensitive lipase by intermediary lipid metabolites.

Hormone-sensitive lipase (HSL) is inhibited in a non-competitive manner by oleoyl CoA, oleic acid and 2-monopalmitoylglycerol, 50% inhibition being observed at concentrations of approx. 0.1 microM, 0.5 microM and 500 microM, respectively. HSL is a key enzyme in lipid metabolism, mobilising triacylglycerol and cholesterol ester stores in several tissues. Feedback inhibition of HSL by oleoyl CoA and oleic acid may therefore prevent accumulation of free fatty acids and cholesterol in the cell, whereas 2-monoacylglycerol may act as a feedback inhibitor if the capacity of monoacylglycerol lipase is exceeded.     

Differences in marker expression among branched histiocytic cells in T-cell areas of the lymphoreticular system and among their epidermis- and mucosa-associated equivalents

Summary Branched histiocytic cells of the epidermis, the oral and anal mucosa, the tonsillar crypt epithelium, the thymus and of the T-cell-dependent areas of lymph node, spleen, and tonsil were examined with immunohistochemical single- and double-staining techniques. The markers used were a monoclonal anti-T6-antibody, a monoclonal anti-HLA-DR-antibody, heteroantiserum to S-100 protein and peanut agglutinin. Anti-HLA-DR and peanut agglutinin reacted with a considerable number of branched histiocytic cells, whereas anti-T6 and anti-S-100 protein only stained relatively small subpopulations. Concerning the population of branched histiocytic cells, double-staining revealed that the tissue distributions of all the markers used overlapped each other to various degrees; this was demonstrated by the different numbers of double-stained cells obtained in the experiments using all six possible combinations of primary reagents. The number of branched histiocytic cells co-expressing the markers varied depending upon marker combinations, types of tissue and microenvironment. We suggest that much of the immunologic phenotype of branched histiocytic cells is dynamic rather than static.Abbreviations used BHCs branched histiocytic cells - anti-T6 monoclonal antibody to T6 antigen - anti-HLA-DR monoclonal antibody to HLA-DR - anti-S-100p antiserum to S-100 protein - (anti-)PNA (anti-)peanut agglutinin - GAM goat anti-mouse IgG - RAM rabbit anti-mouse IgG - GAR-AP alkaline phosphatase-conjugated goat anti-rabbit Ig - SAR porcine anti-rabbit Ig - PAP peroxidase-anti-peroxidase complex - APAAP alkaline phosphataseanti-alkaline phosphatase complex - iAP indirect alkaline phosphatase - AEC 3-amino-9-ethylcarbazole - FB fast blue BB salt - levamisole L[-]2,3,5,6-tetrahydro-6-phenylimidazo[2,1-b]thiazole - DMF NN-dimethylformamide - PBS phosphate-buffered saline solution - + positive reaction of a cell with a resp. marker - – negative reaction of a cell with a resp. marker This work was supported by the German Research Foundation (DFG: Mo.384/1-2)     

Der Mann aus dem Eis

New scientific findings on the Iceman The Iceman, commonly referred to as Ötzi, is the world's oldest glacier mummy and one of the best studied ancient humans in the world. Since the discovery of the 5300-year-old Copper Age individual in 1991, at the Tisenjoch in the Eastern Italian Alps, a variety of morphological, radiological, and molecular analyses have been applied that revealed important insights into his ancestry, his life habits and the circumstances surrounding his violent death. In more recent research, the mummy was subjected to modern research methodologies focusing on high-throughput sequence analysis of ancient biomolecules (DNA, proteins, lipids) that are still found to be preserved in his mummified tissues. Thereby, a genetic predisposition for increased risk for coronary heart disease and the stomach pathogen Helicobacter pylori were detected. This application of innovative “-omics” technologies have allowed the reconstruction of his last meal, that was mainly composed of fat and game meat from wild animals supplemented with cereals from einkorn.     

Structural changes and relaxations monitored by luminescence

Luminescence data have often been used to study imperfections and to characterize lattice distortions because the signals are sensitive to changes of structure and composition. Previous studies have included intentionally added probe ions such as rare earth ions to sense distortions in local crystal fields caused by modified structural environments. An under‐exploited extension of this approach was to use luminescence to monitor crystalline phase changes. A current overview of this new and powerful technique shows that continuous scanning of the sample temperatures immediately offered at least three types of signatures for phase transitions. Because of high sensitivity, luminescence signals were equally responsive to structural changes from inclusions and nanoparticles. These coupled to the host material via long‐range interactions and modified the host signals. Two frequently observed examples that are normally overlooked are from nanoparticle inclusions of water and CO_2. Examples also indicated that phase transitions were detected in more diverse materials such as superconductors and fullerenes. Finally, luminescence studies have shown that in some crystalline examples, high dose ion implantation of surface layers could induce relaxations and/or structural changes of the entire underlying bulk material. This was an unexpected result and therefore such a possibility has not previously been explored. However, the implications for ion implication are significant and could be far more general than the examples mentioned here. Copyright © 2012 John Wiley & Sons, Ltd.     

Osteogenesis imperfecta

Osteogenesis imperfecta (OI) is the most frequently occurring congenital disorder with an increased fracture rate and systemic skeletal involvement. The vast majority of patients have an autosomal dominant form of OI resulting from a mutation in one of the two type I collagen genes COL1A1 or COL1A2. Since 2006, eight genes for autosomal recessive forms of the disorder have been identified, as well as one additional gene for autosomal dominant OI. Our knowledge concerning molecular pathophysiology has been substantially broadened, such that the paradigm of OI as a pure ??collagenopathy?? no longer applies and the clinical classification system will have to be revised. Standard therapy for the more severe forms of OI comprises intravenous administration of bisphosphonates. Additional elements of a multimodal therapeutic concept include surgical intervention for bone deformities or fractures and physiotherapy.