Medizin - Open Access LMU - Teil 21/22

Tissue-Specific and Minor Inter-Individual Variation in Imprinting of IGF2R Is a Common Feature of Bos taurus Concepti and Not Correlated with Fetal Weight

The insulin-like growth factor 2 receptor (IGF2R) is essential for prenatal growth regulation and shows gene dosage effects on fetal weight that can be affected by in-vitro embryo culture. Imprinted maternal expression of murine Igf2r is well documented for all fetal tissues excluding brain, but polymorphic imprinting and biallelic expression were reported for IGF2R in human. These differences have been attributed to evolutionary changes correlated with specific reproductive strategies. However,...

Target analyte quantification by isotope dilution LC-MS/MS directly referring to internal standard concentrations-validation for serum cortisol measurement

Isotope dilution LC-MS/MS methods used in the clinical laboratory typically involve multi-point external calibration in each analytical series. Our aim was to test the hypothesis that determination of target analyte concentrations directly derived from the relation of the target analyte peak area to the peak area of a corresponding stable isotope labelled internal standard compound [direct isotope dilution analysis (DIDA)] may be not inferior to conventional external calibration with respect to ...

Confocal laser endomicroscopy in head and neck cancer: steps forward?

Purpose of review Confocal laser endomicroscopy (CLE) is a novel, noninvasive technique used to obtain microanatomical images of the inner lining of hollow organs. It has been used in a variety of clinical specialties to aid in the diagnosis and treatment planning of inflammatory and neoplastic processes. Our intent is to provide an up-to-date review of the literature in the setting of head and neck diseases as well as describing our own initial results and areas of future research. Recent findi...

Persistence of Symptoms in Primary Somatoform Vertigo and Dizziness A Disorder "Lost" in Health Care?

The aim of this study was to perform a 3-year follow-up of primary somatoform vertigo and dizziness (SVD) regarding health care use and treatment. Ninety-two patients with dizziness underwent detailed vestibular neurophysiological testing and a Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Psychometric assessments comprised the Vertigo Symptom Scale, the Vertigo Handicap Questionnaire, the SCL-90-R, and the Short-Form-36 Health Survey. A...

Determinants of Long-term Protection After Hepatitis B Vaccination in Infancy: A Meta-analysis

Background: The duration of protection after hepatitis B vaccination in early infancy is unclear and may be related to vaccination schedule, dosage, vaccine type and population characteristics. Factors potentially influencing waning immunity were assessed. Methods: A systematic review was performed. The main outcomes were prevalence of anti-hepatits B antibodies >= 10 mIU/mL after primary or booster vaccination. Factors potentially influencing protection were assessed in an adjusted random-ef...

Quantification of Contrast Recognizability in Sequential Epiretinal Membrane Removal and Internal Limiting Membrane Peeling in Trypan Blue-Assisted Macular Surgery

Purpose: To evaluate the selectivity and strength of intraoperative trypan blue staining during removal of epiretinal membranes (ERMs) and the internal limiting membrane. Methods: Based on intraoperative videos, 51 consecutive chromovitrectomies in 51 patients with macular holes, macular pucker, vitreomacular traction syndromes, or persistent macular edema were retrospectively studied. Fifteen subjects underwent trypan blue, 14 indocyanine green, and 22 brilliant blue G chromovitrectomy. The mai...

Development of a Sensitive Phospho-p70 S6 Kinase ELISA to Quantify mTOR Proliferation Signal Inhibition

Background: Drug blood levels can only serve as a surrogate because of the lack of information on the drug's direct pharmacological effects in the individual patient. Measurement of the mammalian target of rapamycin (mTOR) activity dependent on the phosphorylation status of p70 S6 kinase (p70 S6K) offers a practical way for monitoring pharmacodynamic drug activity, with the potential to better assess the state of immunosuppression in individual patients. Material and Methods: Here, we establishe...

Atherosclerosis: cell biology and lipoproteins-focus on anti-inflammatory mechanisms as therapeutic options

Treatment with 4-aminopyridine improves upper limb tremor of a patient with multiple sclerosis: a video case report

Here we report the case of a 44-year old patient with a progressive MS whose upper limb tremor was markedly reduced under treatment with 4-aminopyridine, as documented in a Tremor Activities of Daily Living questionnaire and in the 9-Hole Peg test. Hand accelerations decreased in the left hand from 10.9 m/sec2 to 2.2 m/sec2 and in the right hand from 4.2 m/sec2 to 0.9 m/sec(2). This case report indicates for the first time that 4-aminopyridine might be effective in the symptomatic treatment of t...

The Munich ChronoType Questionnaire for Shift-Workers (MCTQ(Shift))

Sleep is systematically modulated by chronotype in day-workers. Therefore, investigations into how shift-work affects sleep, health, and cognition may provide more reliable insights if they consider individual circadian time (chronotype). The Munich ChronoType Questionnaire (MCTQ) is a useful tool for determining chronotype. It assesses chronotype based on sleep behavior, specifically on the local time of mid-sleep on free days corrected for sleep debt accumulated over the workweek (MSFsc). Beca...

Chronotype Modulates Sleep Duration, Sleep Quality, and Social Jet Lag in Shift-Workers

This study explores chronotype-dependent tolerance to the demands of working morning, evening, and night shifts in terms of social jet lag, sleep duration, and sleep disturbance. A total of 238 shift-workers were chronotyped with the Munich ChronoType Questionnaire for shift-workers (MCTQ(Shift)), which collects information about shift-dependent sleep duration and sleep timing. Additionally, 94 shift-workers also completed those items of the Sleep Questionnaire from the Standard Shift-Work Index...

Health effects of infant feeding: Information for parents in leaflets and magazines in five European countries

Parents' decisions about whether to breastfeed their infant, and when to introduce complementary foods, are important public health issues. Breastfeeding has beneficial health effects and is widely promoted. Leaflets and magazine articles on infant feeding were collected in 2005, in five European countries (England, Finland, Germany, Hungary, Spain), and screened for statements that link feeding behaviours to infant health outcomes. A total of 127 leaflets contained 512 statements (0.38/publishe...

Activation of pregnane X receptor inhibits experimental dermal fibrosis

Objective: To assess the antifibrotic effects of pregnane X receptors (PXRs) in experimental dermal fibrosis. Methods: The antifibrotic effects of PXR activation by 5-pregnen-3 beta-ol-20-one-16 alpha-carbonitrile (PCN) were studied in the bleomycin model for prevention of dermal fibrosis and the modified bleomycin model for the treatment of established bleomycin-induced dermal fibrosis. Activation of canonical transforming growth factor (TGF)beta signalling was analysed by immunofluorescence st...

Of flies, mice and men: a systematic approach to understanding the early life origins of chronic lung disease

Despite intensive research efforts, the aetiology of the majority of chronic lung diseases (CLD) in both, children and adults, remains elusive. Current therapeutic options are limited, providing only symptomatic relief, rather than treating the underlying condition, or preventing its development in the first place. Thus, there is a strong and unmet clinical need for the development of both, novel effective therapies and preventative strategies for CLD. Many studies suggest that modifications of ...

Caveolin-1 protects B6129 mice against Helicobacter pylori gastritis.

Caveolin-1 (Cav1) is a scaffold protein and pathogen receptor in the mucosa of the gastrointestinal tract. Chronic infection of gastric epithelial cells by Helicobacter pylori (H. pylori) is a major risk factor for human gastric cancer (GC) where Cav1 is frequently down-regulated. However, the function of Cav1 in H. pylori infection and pathogenesis of GC remained unknown. We show here that Cav1-deficient mice, infected for 11 months with the CagA-delivery deficient H. pylori strain SS1, develop...

Spectrum of novel mutations found in Waardenburg syndrome types 1 and 2: implications for molecular genetic diagnostics

Objectives: Till date, mutations in the genes PAX3 and MITF have been described in Waardenburg syndrome (WS), which is clinically characterised by congenital hearing loss and pigmentation anomalies. Our study intended to determine the frequency of mutations and deletions in these genes, to assess the clinical phenotype in detail and to identify rational priorities for molecular genetic diagnostics procedures. Design: Prospective analysis. Patients: 19 Caucasian patients with typical features of ...

Human Mas-related G protein-coupled receptors-X1 induce chemokine receptor 2 expression in rat dorsal root ganglia neurons and release of chemokine ligand 2 from the human LAD-2 mast cell line

Primate-specific Mas-related G protein-coupled receptors-X1 (MRGPR-X1) are highly enriched in dorsal root ganglia (DRG) neurons and induce acute pain. Herein, we analyzed effects of MRGPR-X1 on serum response factors (SRF) or nuclear factors of activated T cells (NFAT), which control expression of various markers of chronic pain. Using HEK293, DRG neuron-derived F11 cells and cultured rat DRG neurons recombinantly expressing human MRGPR-X1, we found activation of a SRF reporter gene construct an...

Free Breathing Real-Time Cardiac Cine Imaging With Improved Spatial Resolution at 3 T

Objectives: The aim of this study was to evaluate free-breathing single-shot real-time cine imaging for functional cardiac imaging at 3 +/- with increased spatial resolution. Special emphasis of this study was placed on the influence of parallel imaging techniques. Materials and Methods: Gradient echo phantom images were acquired with GRAPPA and modified SENSE reconstruction using both integrated and separate reference scans as well as TGRAPPA and TSENSE. In vivo measurements were performed for ...

Methodological Approaches for Dietary Intake Assessment in Formula-fed Infants

Background and Objective: The estimation of dietary intake remains a challenge in human nutritional studies. In infants, the use of food diaries (FDs) is a suitable method already validated; however, this method is not exempt from error. In formula-fed infants, dilution of powdered formulas may produce errors. Our aim was to develop and validate standard operating procedures (SOPs) for the assessment of dietary intake in formula-fed infants, attending potential sources of error. Methods: We anal...

Dynamic and Static Magnetic Resonance Angiography of the Supra-aortic Vessels at 3.0 T Intraindividual Comparison of Gadobutrol, Gadobenate Dimeglumine, and Gadoterate Meglumine at Equimolar Dose

Purpose: The purpose of this study was the intraindividual comparison of a 1.0 M and two 0.5 M gadolinium-based contrast agents (GBCA) using equimolar dosing in dynamic and static magnetic resonance angiography (MRA) of the supra-aortic vessels. Materials and Methods: In this institutional review board-approved study, a total of 20 healthy volunteers (mean +/- SD age, 29 +/- 6 years) underwent 3 consecutive supra-aortic MRA examinations on a 3.0 T magnetic resonance system. The order of GBCA (Ga...

Noninvasive Analysis of Synthetic and Decellularized Scaffolds for Heart Valve Tissue Engineering

Microcomputed tomography (mu-CT) is a nondestructive, high-resolution, three-dimensional method of analyzing objects. The aim of this study was to evaluate the feasibility of using mu-CT as a noninvasive method of evaluation for tissue-engineering applications. The polyurethane aortic heart valve scaffold was produced using a spraying technique. Cryopreserved/thawed homograft and biological heart valve were decellularized using a detergent mixture. Human endothelial cells and fibroblasts were de...

Antithrombin Reduces Inflammation and Microcirculatory Perfusion Failure in Closed Soft-Tissue Injury and Endotoxemia

Background: Closed soft-tissue trauma leads to activation of the coagulation cascade and is often complicated by systemic inflammation and infection. Previous investigations have shown potent anti-inflammatory properties of antithrombin. We herein report on the action of antithrombin on skeletal muscle injury in experimental endotoxemia. Materials and Methods: By using a pneumatically driven computer-controlled impact device, closed soft-tissue trauma was applied on the left hind limb of pentoba...

The pharmacokinetics, safety and efficacy of tenofovir and emtricitabine in HIV-1-infected pregnant women

Objective: To describe the pharmacokinetics of tenofovir and emtricitabine in the third trimester of pregnant HIV-infected women and at postpartum. Design: A nonrandomized, open-label, multicentre phase IV study in HIV-infected pregnant women recruited from HIV treatment centres in Europe. Methods: HIV-infected pregnant women treated with the nucleotide/nucleoside analogue reverse transcriptase inhibitors (NRTIs) tenofovir disoproxil fumarate (TDF 300 mg; equivalent to 245 mg tenofovir disoproxi...

CD40-CD40L: Linking pancreatic, adipose tissue and vascular inflammation in type 2 diabetes and its complications

Numerous epidemiological studies have consistently demonstrated the strong association between type 2 diabetes mellitus (T2DM) and an increased risk to develop cardiovascular disease. The pathogenesis of T2DM and its complications are characterized by pancreatic, adipose tissue and vascular inflammation. CD40 and CD40L, members of the tumour necrosis factor (receptor) TNF(R) family, are well known for their role in immunity and inflammation. Here we give an overview on the role of CD40-CD40L int...

Increased Serum Concentrations of Circulating Glycocalyx Components in HELLP Syndrome Compared to Healthy Pregnancy: An Observational Study

Severe inflammation has been shown to induce a shedding of the endothelial glycocalyx (EGX). Inflammatory cytokines, such as tumor necrosis factor alpha (TNF-alpha), impede the thickness of the EGX. While a controlled inflammatory reaction occurs already in normal pregnancy, women with hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome had an exaggerated inflammatory response. This study investigates the shedding of the glycocalyx during normal pregnancy and in women with HELLP...

Genome-wide significant association of ANKRD55 rs6859219 and multiple sclerosis risk

Association of Galectin Single Nucleotide Polymorphisms with Autoimmune Diseases

Impaired Natural Killer Cell Function in DOCK8 Deficiency

Sample size determinations in original research protocols for randomised clinical trials submitted to UK research ethics committees: review

Objectives To assess the completeness of reporting of sample size determinations in unpublished research protocols and to develop guidance for research ethics committees and for statisticians advising these committees. Design Review of original research protocols. Study selection Unpublished research protocols for phase IIb, III, and IV randomised clinical trials of investigational medicinal products submitted to research ethics committees in the United Kingdom during 1 January to 31 December 20...

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7 x 10(-8), HR = 1.14, 95% CI: 1.09-...