Vitamin A abuse: development of cirrhosis despite cessation of vitamin A. A six-year clinical and histopathologic follow-up.

We report the case of a 35-year-old man who contracted vitamin A-induced liver cirrhosis. Five years before, he had been investigated for vitamin A-induced non-cirrhotic portal hypertension. In this case, the clinical and histopathologic evolution from non-cirrhotic portal hypertension to cirrhosis was documented. In spite of the cessation of pharmaceutical vitamin A intake, the disease progressed. Therapy with colchicine and phenobarbital apparently did not influence evolution to cirrhosis. This suggests that vitamin A can trigger largely unknown mechanisms of liver fibrosis which seem to be self-perpetuating.     

Prognostic factors in allogeneic transplantation for patients with high-risk multiple myeloma after reduced intensity conditioning

OBJECTIVES: The aim of this study was to identify prognostic factors for outcome of high-risk patients with multiple myeloma after allogeneic transplantation prepared by reduced intensity conditioning (RIC). MATERIALS AND METHODS: Data from 45 consecutive patients (median age 52 years, range 38-68), who received grafts from a sibling (n = 34) or unrelated donor (n = 11) were analyzed. Fourteen patients received an RIC allotransplant while chemosensitive (>/=partial remission [PR]), whereas 31 chemoresistant patients (相似文献   

Isolated rupture of the left atrial appendage after blunt chest trauma

Traumatic cardiac damage is caused by penetrating or blunt injury.The majority of disruptures in blunt trauma are the result of deceleration traumas.We present the case of an 8-year-old boy who fell off his horse. Afterwards the horse stepped on his chest. He was successfully treated for pericardial tamponade due to an isolated left appendage rupture. The lesion was probably caused by a sudden elevated intra-atrial blood pressure during chest compression.     

Adenoviral low density lipoprotein receptor attenuates progression of atherosclerosis and decreases tissue cholesterol levels in a murine model of familial hypercholesterolemia

Familial hypercholesterolemia is an autosomal codominant disease characterized by high concentrations of pro-atherogenic lipoproteins and premature atherosclerosis secondary to low density lipoprotein receptor (LDLr) deficiency. In the current study, the effects of gene transfer with 5 x 10(10) particles of E1E3E4-deleted adenoviral vectors expressing the LDLr (AdLDLr) or VLDLr (AdVLDLr) under control of the hepatocyte-specific human alpha(1)-antitrypsin promoter and 4 copies of the human apo E enhancer in C57BL/6 LDLr(-/-) mice were investigated. Evaluation was performed in both sexes and in mice fed either standard chow or an atherogenic diet containing 0.2% cholesterol and 10% coconut oil. Compared to control mice, AdLDLr and AdVLDLr persistently decreased plasma non-HDL cholesterol in both sexes and on both diets. Six months after LDLr gene transfer in mice fed the atherogenic diet, average intimal area was 2.5-fold (p<0.01) and 3.2-fold (p<0.001) lower in male and female mice, respectively, compared to controls. In mice fed standard chow, intimal area was reduced 22-fold (p<0.001) and 21-fold (p<0.001) after LDLr gene transfer in male and female mice, respectively. We show that non-HDL lipoproteins are more atherogenic in female mice, independent of sex differences of plasma HDL cholesterol levels, and that saturated fat does not have an effect on atherosclerosis independent of plasma cholesterol levels. Finally, quantification of tissue cholesterol levels indicates that AdLDLr does not induce cholesterol accumulation in the liver and reduces cholesterol content in the myocardium, quadriceps muscle and kidney. In conclusion, hepatocyte-specific LDLr gene transfer significantly improves cholesterol homeostasis in LDLr(-/-) mice.     

Hypoxia drives murine neutrophil protein scavenging to maintain central carbon metabolism

Limiting dysfunctional neutrophilic inflammation while preserving effective immunity requires a better understanding of the processes that dictate neutrophil function in the tissues. Quantitative mass-spectrometry identified how inflammatory murine neutrophils regulated expression of cell surface receptors, signal transduction networks, and metabolic machinery to shape neutrophil phenotypes in response to hypoxia. Through the tracing of labeled amino acids into metabolic enzymes, proinflammatory mediators, and granule proteins, we demonstrated that ongoing protein synthesis shapes the neutrophil proteome. To maintain energy supplies in the tissues, neutrophils consumed extracellular proteins to fuel central carbon metabolism. The physiological stresses of hypoxia and hypoglycemia, characteristic of inflamed tissues, promoted this extracellular protein scavenging with activation of the lysosomal compartment, further driving exploitation of the protein-rich inflammatory milieu. This study provides a comprehensive map of neutrophil proteomes, analysis of which has led to the identification of active catabolic and anabolic pathways that enable neutrophils to sustain synthetic and effector functions in the tissues.     

Morphologic Heterogeneity of Renal Light-Chain Deposition Disease

Light-chain deposition disease (LCDD) of the kidney is defined as deposition of monotypic light chains (LC) within glomerular (GBM) and tubular (TBM) basement membranes. The morphologic features of pure renal LCDD have been presented only in case reports or small series. The aim of this study was to perform a comprehensive evaluation of the light (LM), immunofluorescence (IF), and electron microscopic (EM) features of pure renal LCDD in a large series of biopsies. Out of 46 cases assembled, 42 had multiple myeloma, 2 had monoclonal gammopathy of unknown significance, and in 2 patients no lymphoproliferative disease was identified. The most common LM lesion of LCDD, nodular glomerulosclerosis, was present in only 14 (30%) cases. GBM and/or TBM thickening was found in 3 (6%), mild to moderate mesangial matrix increase in 12 (23%), and unremarkable glomeruli and tubules were seen in 15 (32%) cases. Forty-two had IF and 40 (92%) showed characteristic linear LC immunoreactivity (24 kappa, 16 lambda) along GBM and/or TBM. Among 39 cases in which IF and EM was available, 25 (64%) were positive by both. Two (6%) were negative by IF, but had deposits by EM. In 12 (30%) with immunoreactivity to LC (4 kappa, 8 lambda), no deposits were identified ultrastructurally. This study shows heterogeneous LM lesions in pure LCDD cases. LM alone may be suspicious but not diagnostic of LCDD. Immunofluorescence is more sensitive than EM for detection of LC for the definitive diagnosis of LCDD. This study supports the importance of utilizing kappa and lambda stains in the routine IF panel for diagnosis of LCDD.     

Mutational analysis of TARDBP in Parkinson's disease

Mutations in TAR DNA-binding protein (TARDBP) are associated with heterogenic phenotypes, including amyotrophic lateral sclerosis, frontotemporal dementia, and Parkinson's disease. In this study, we investigated the presence of TARDBP mutations in a cohort of 429 Dutch patients with Parkinson's disease. Though we detected 1 silent mutation, p.S332S, no missense mutations were present in our cohort. Our findings, therefore, demonstrate that TARDBP mutations do not appear to contribute to the pathogenesis of Parkinson's disease in The Netherlands.     

Identification of Medically Relevant Species of Arthroconidial Yeasts by Use of Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry

Matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) was used for an extensive identification study of arthroconidial yeasts, using 85 reference strains from the CBS-KNAW yeast collection and 134 clinical isolates collected from medical centers in Qatar, Greece, and Romania. The test set included 72 strains of ascomycetous yeasts (Galactomyces, Geotrichum, Saprochaete, and Magnusiomyces spp.) and 147 strains of basidiomycetous yeasts (Trichosporon and Guehomyces spp.). With minimal preparation time, MALDI-TOF MS proved to be an excellent diagnostic tool that provided reliable identification of most (98%) of the tested strains to the species level, with good discriminatory power. The majority of strains were correctly identified at the species level with good scores (>2.0) and seven of the tested strains with log score values between 1.7 and 2.0. The MALDI-TOF MS results obtained were consistent with validated internal transcribed spacer (ITS) and/or large subunit (LSU) ribosomal DNA sequencing results. Expanding the mass spectrum database by increasing the number of reference strains for closely related species, including those of nonclinical origin, should enhance the usefulness of MALDI-TOF MS-based diagnostic analysis of these arthroconidial fungi in medical and other laboratories.     

A word of hope for ataxia trials in COVID-19 time and beyond

Journal of Neurology - The coronavirus disease 2019 (COVID-19) crisis confronted us, like many researchers worldwide, with an unforeseen challenge during the final stages of a randomized controlled...