Increased risk of death associated with the use of proton-pump inhibitors in patients with dementia and controls - a pharmacoepidemiological claims data analysis.

BACKGROUND AND PURPOSE: The use of proton-pump inhibitors (PPIs) was reported to be associated with increased mortality risk and has been proposed as a potential risk factor for neurodegenerative diseases. We aimed to assess the impact of PPI use on survival in patients with dementia as compared with controls. METHODS: This register-based control-matched cohort study included 28 428 patients with dementia ascertained by the prescription of antidementia drugs and two control individuals matched by sex, age and area of residence for each patient with dementia during the study period from 1 January 2005 to 30 June 2016. Cumulative defined daily doses (DDDs) of PPIs were extracted from the health insurance prescription registries. A multivariate Cox regression model for non-proportional hazards was used to analyse mortality risk in dependence of PPI exposure, which was limited to 1 year preceding the date of cohort entry (index date) in order to avoid immortal time bias. RESULTS: The PPI exposure of 100 DDDs in the year before the index date was associated with an increased mortality risk in patients with dementia (adjusted hazard ratio, 1.07; 95% confidence intervals, 1.03-1.12), but also in controls (adjusted hazard ratio, 1.47; 95% confidence intervals, 1.31-1.64). The mortality risk in relation to PPI use was significantly lower in patients with dementia as compared with controls (P < 0.0001) and highest in the first 2 years after the index date in both cohorts. CONCLUSIONS: Our findings promote more stringent pharmacovigilance strategies to avoid PPI use in cases lacking a clear indication for therapy or where potential risks outweigh the benefits.

Characterization of the Hydra lamin and its gene: A molecular phylogeny of metazoan lamins.

We report sequences for nuclear lamins from the teleost fish Danio and six invertebrates. These include two cnidarians (Hydra and Tealia), one priapulid, two echinoderms, and the cephalochordate Branchiostoma. Combining these results with earlier data on Drosophila, Caenorhabditis elegans, and various vertebrates, the following conclusions on lamin evolution can be drawn. First, all invertebrate lamins resemble in size the vertebrate B-type lamin. Second, all lamins described previously for amphibia, birds and mammals as well as the first lamin of a fish, characterized here, show a cluster of 7 to 12 acidic residues in the tail domain. Since this acidic cluster is absent from all invertebrate lamins including that of the cephalochordate Branchiostoma, it was acquired with the vertebrate lineage. The larger A-type lamin of differentiated cells must have arisen subsequently by gene duplication and insertion of an extra exon. This extra exon of the vertebrate A-lamins is the only major change in domain organization in metazoan lamin evolution. Third, the three introns of the Hydra and Priapulus genes correspond in position to the last three introns of vertebrate B-type lamin genes. Thus the entirely different gene organization of the C. elegans and Drosophila Dmo genes seems to reflect evolutionary drift, which probably also accounts for the fact that C. elegans has the most diverse lamin sequence. Finally we discuss the possibility that two lamin types, a constitutively expressed one and a developmentally regulated one, arose independently on the arthropod and vertebrate lineages.

Molecular phylogeny of metazoan intermediate filament proteins.

We have cloned cytoplasmic intermediate filament (IF) proteins from a large number of invertebrate phyla using cDNA probes, the monoclonal antibody IFA, peptide sequence information, and various RT-PCR procedures. Novel IF protein sequences reported here include the urochordata and nine protostomic phyla, i.e., Annelida, Brachiopoda, Chaetognatha, Echiura, Nematomorpha, Nemertea, Platyhelminthes, Phoronida, and Sipuncula. Taken together with the wealth of data on IF proteins of vertebrates and the results on IF proteins of Cephalochordata, Mollusca, Annelida, and Nematoda, two IF prototypes emerge. The L-type, which includes 35 sequences from 11 protostomic phyla, shares with the nuclear lamins the long version of the coil 1b subdomain and, in most cases, a homology segment of some 120 residues in the carboxyterminal tail domain. The S-type, which includes all four subfamilies (types I to IV) of vertebrate IF proteins, lacks 42 residues in the coil 1b subdomain and the carboxyterminal lamin homology segment. Since IF proteins from all three phyla of the chordates have the 42-residue deletion, this deletion arose in a progenitor prior to the divergence of the chordates into the urochordate, cephalochordate, and vertebrate lineages, possibly already at the origin of the deuterostomic branch. Four phyla recently placed into the protostomia on grounds of their 18S rDNA sequences (Brachiopoda, Nemertea, Phoronida, and Platyhelminthes) show IF proteins of the L-type and fit by sequence identity criteria into the lophotrochozoic branch of the protostomia.

Homologues of vertebrate type I, II and III intermediate filament (IF) proteins in an invertebrate: the IF multigene family of the cephalochordate Branchiostoma.

We searched for functional homologues of the four subfamilies of vertebrate cytoplasmic intermediate filament (IF) proteins in the cephalochordate Branchiostoma. The epidermis contains in addition to IF proteins C2 and D1 two novel IF proteins E1 and E2. Both sequence comparisons as well as the obligatory heteropolymer formation by the recombinant proteins identify E1 as a type I keratin and E2 and D1 as type II keratins. In contrast the non-epidermal B1 forms as type III homologue homopolymeric IF. We propose that type I-III diversification of IF proteins is a property of the chordate branch of metazoa and discuss a possible origin of type IV neurofilaments.

[3 cases of eosinophilic leukemia with atypical granulation in the eosinophils and neutrophils]. / Dre Fälle von Eosinophilenleukämie mit atypischer Granulation in Eosinophilen und Neutrophilen

Three patients with eosinophilic leukemia and atypical granulation in the eosinophils are described. A remarkable light and electron microscopic finding was the appearance of enormous granules in the neurtophils and eosinophils. In addition the usual anomalies seen in acute leukemia, for example asynchronisation in cell maturation, fibrillar bundles, shrinkage of nucleolus and cell organelles, signs of degeneration and also the auer-rods characteristic of AML are observed.

[Spontaneous radial segmentation of the nuclei of myeloblasts in a case of chronic granulocytic leukemia during blastic crisis. an electromicroscopical study (author's transl)]. / Spontane radialsegmentation de myeloblastenkerne einer chronis"h-myeloischen leukämie im blastenschub eine elektronenmikroskopische studie

By means of electron microscopy, myeloblasts with spontaneous radial segmentation of the nuclei from a patient with micromegakaryotic chronic myelosis in the blastic crisis were analysed. The centriol was found in the center of the cells and microtubules were found between the segments of the nucleus. These observations support the hypothesis that spontaneous radial segmentations of the nuclei of tumor cells is associated with a contractile process of the microtubules with split the nucleus.