Implantable defibrillator event rates in patients with idiopathic dilated cardiomyopathy, nonsustained ventricular tachycardia on Holter and a left ventricular ejection fraction below 30%

AbstractObjectivesThis study investigated the incidence of appropriate implantable cardioverter defibrillator (ICD) interventions for ventricular tachycardia (VT) or ventricular fibrillation (VF) in patients with idiopathic dilated cardiomyopathy (IDC) and nonsustained VT in the presence of a left ventricular ejection fraction below 30%, versus in patients with syncope and patients with a history of VT or VF.BackgroundTo date, only limited information is available about the prophylactic use of ICDs in patients with IDC.MethodsFrom January 1993 to July 2000, 101 patients with IDC underwent implantation of ICDs with electrogram storage capability at our institution. Patients were placed into one of three groups according to their clinical presentation: asymptomatic or mildly symptomatic nonsustained VT in the presence of a left ventricular ejection fraction ≤30% (49 patients, prophylactic group), unexplained syncope or near syncope (26 patients, syncope group) and a history of sustained VT or VF (26 patients, VT/VF group).ResultsDuring 36 ± 22 months follow-up, 18 of 49 patients (37%) in the prophylactic group received appropriate shocks for VT or VF, compared with 8 of 26 patients (31%) in the syncope group and with 9 of 26 patients (35%) of the VT/VF group. Multivariate Cox analysis of baseline clinical variables identified left ventricular ejection fraction, atrial fibrillation and a history of sustained VT or VF as predictors for appropriate ICD interventions during follow-up.ConclusionPatients with IDC and prophylactic ICD implantation for nonsustained VT in the presence of a left ventricular ejection fraction ≤30% had an incidence of appropriate ICD interventions similar to that of patients with a history of syncope or sustained VT or VF. These findings indicate that ICDs may have a role in not only secondary but also primary prevention of sudden death in IDC

Rituximab Mediates a Strong Elevation of B-Cell-Activating Factor Associated with Increased Pathogen-Specific IgG but Not Autoantibodies in Pemphigus Vulgaris

Pemphigus vulgaris (PV) is a severe autoimmune disease affecting the skin and mucous membranes, characterized by autoantibodies mainly against desmoglein 3 (dsg3). This study investigated the effects of different treatment options on two B-cell mediators, B-cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL), in 19 PV patients on immunosuppressive drugs alone or in combination with immunoadsorption and anti-CD20 antibody, respectively. Serum BAFF and APRIL levels, circulating desmoglein-reactive autoantibodies, and serum IgG specific for varicella-zoster virus (VZV) and Epstein–Barr virus (EBV) were determined by ELISA before and at different time points after initiation of the respective therapy. In contrast to immunosuppressive therapy alone and in combination with adjuvant immunoadsorption, respectively, rituximab treatment led to a strong and significant elevation of BAFF, but not of APRIL levels, which normalized upon recovery of peripheral CD19+ B cells. Moreover, rituximab treatment led to a statistically significant increase of anti-VZV-IgG and anti-EBV-IgG titers, whereas anti-dsg1 and -3 specific autoantibody titers decreased significantly. Our results suggest that elevated BAFF levels might exert a differential effect on the induction of autoreactive versus pathogen-specific IgG antibody production in PV patients, possibly due to promotion of antibody release of pathogen-specific long-lived plasma cells

A new and reliable culture system for superficial low-grade urothelial carcinoma of the bladder

Several bladder cancer culture systems have been developed in recent years. However, reports about successful primary cultures of superficial urothelial carcinomas (UC) are sparse. Based on the specific growth requirements of UC described previously, we developed a new and reliable culture system for superficial low-grade UC. Between November 2002 and April 2006, 64 primary cultures of bladder cancer specimens were performed. After incubating the specimens overnight in 0.1% ethylenediaminetetraacetic acid solution, tumour cells could easily be separated from the submucosal tissue. Subsequently, cells were seeded in a low-calcium culture medium supplemented with 1% serum, growth factors, non-essential amino acids and glycine. The malignant origin of the cultured cells was demonstrated by spectral karyotyping. Overall culture success rate leading to a homogenous tumour cell population without fibroblast contamination was 63%. Culture success could be remarkably enhanced by the addition of glycine to the culture medium. Interestingly, 86.4% of pTa tumours were cultured successfully compared to only 50% of the pT1 and 38% of advanced stage tumours, respectively. G1 and G2 tumours grew significantly better than G3 tumours (86, 73 and 41%, respectively). Up to three passages of low-grade UC primary cultures were possible. We describe a new and reliable culture system, which is highly successful for primary culture and passage of low-grade UC of the bladder. Therefore, this culture system can widely be used for functional experiments on early stage bladder cance

Comparison of 6 % hydroxyethyl starch and 5 % albumin for volume replacement therapy in patients undergoing cystectomy (CHART): study protocol for a randomized controlled trial

Background The use of artificial colloids is currently controversial, especially in Central Europe Several studies demonstrated a worse outcome in intensive care unit patients with the use of hydroxyethyl starch. This recently even led to a drug warning about use of hydroxyethyl starch products in patients admitted to the intensive care unit. The data on hydroxyethyl starch in non–critically ill patients are insufficient to support perioperative use. Methods/Design We are conducting a single-center, open-label, randomized, comparative trial with two parallel patient groups to compare human albumin 5 % (test drug) with hydroxyethyl starch 6 % 130/0.4 (comparator). The primary endpoint is cystatin C ratio, calculated as the ratio of the cystatin value at day 90 after surgery relative to the preoperative value. Secondary objectives are inter alia the evaluation of the influence of human albumin and hydroxyethyl starch on further laboratory chemical and clinical parameters, glycocalyx shedding, intensive care unit and hospital stay and acute kidney injury as defined by RIFLE criteria (risk of renal dysfunction, injury to the kidney, failure of kidney function, loss of kidney function, and end-stage kidney disease) criteria. Discussion There is a general lack of evidence on the relative safety and effects of hydroxyethyl starch compared with human albumin for volume replacement in a perioperative setting. Previously conducted studies of surgical patients in which researchers have compared different hydroxyethyl starch products included too few patients to properly evaluate clinical important outcomes such as renal function. In the present study in a high-risk patient population undergoing a major surgical intervention, we will determine if perioperative fluid replacement with human albumin 5 % will have a long-term advantage over a third-generation hydroxyethyl starch 130/0.4 on the progression of renal dysfunction until 90 days after surgery

Non-invasive detection of animal nerve impulses with an atomic magnetometer operating near quantum limited sensitivity

Magnetic fields generated by human and animal organs, such as the heart, brain and nervous system carry information useful for biological and medical purposes. These magnetic fields are most commonly detected using cryogenically-cooled superconducting magnetometers. Here we present the frst detection of action potentials from an animal nerve using an optical atomic magnetometer. Using an optimal design we are able to achieve the sensitivity dominated by the quantum shot noise of light and quantum projection noise of atomic spins. Such sensitivity allows us to measure the nerve impulse with a miniature room-temperature sensor which is a critical advantage for biomedical applications. Positioning the sensor at a distance of a few millimeters from the nerve, corresponding to the distance between the skin and nerves in biological studies, we detect the magnetic field generated by an action potential of a frog sciatic nerve. From the magnetic field measurements we determine the activity of the nerve and the temporal shape of the nerve impulse. This work opens new ways towards implementing optical magnetometers as practical devices for medical diagnostics.Comment: Main text with figures, and methods and supplementary informatio

Cholesterol promotes clustering of PI(4,5)P2 driving unconventional secretion of FGF2

FGF2 is a cell survival factor involved in tumor-induced angiogenesis that is secreted through an unconventional secretory pathway based upon direct protein translocation across the plasma membrane. Here, we demonstrate that both PI(4,5)P2-dependent FGF2 recruitment at the inner plasma membrane leaflet and FGF2 membrane translocation into the extracellular space are positively modulated by cholesterol in living cells. We further revealed cholesterol to enhance FGF2 binding to PI(4,5)P2-containing lipid bilayers. Based on extensive atomistic molecular dynamics (MD) simulations and membrane tension experiments, we proposed cholesterol to modulate FGF2 binding to PI(4,5)P2 by (i) increasing head group visibility of PI(4,5)P2 on the membrane surface, (ii) increasing avidity by cholesterol-induced clustering of PI(4,5)P2 molecules triggering FGF2 oligomerization, and (iii) increasing membrane tension facilitating the formation of lipidic membrane pores. Our findings have general implications for phosphoinositide-dependent protein recruitment to membranes and explain the highly selective targeting of FGF2 toward the plasma membrane, the subcellular site of FGF2 membrane translocation during unconventional secretion of FGF2

Isoenergetic Feeding of Low Carbohydrate-High Fat Diets Does Not Increase Brown Adipose Tissue Thermogenic Capacity in Rats

Low-carbohydrate, high-fat (LC-HF) diets are popular for inducing weight loss in overweighed adults. Adaptive thermogenesis increased by specific effects of macronutrients on energy expenditure has been postulated to induce this weight loss. We studied brown adipose tissue (BAT) morphology and function following exposure to different LC-HF diets

Effects of acetyl-DL-leucine on cerebellar ataxia (ALCAT trial): study protocol for a multicenter, multinational, randomized, double-blind, placebo-controlled, crossover phase III trial

BACKGROUND: Cerebellar ataxia (CA) is a frequent and often disabling condition that impairs motor functioning and impacts on quality of life (QoL). No medication has yet been proven effective for the symptomatic or even causative treatment of hereditary or non-hereditary, non-acquired CA. So far, the only treatment recommendation is physiotherapy. Therefore, new therapeutic options are needed. Based on three observational studies, the primary objective of the acetyl-DL-leucine on ataxia (ALCAT) trial is to examine the efficacy and tolerability of a symptomatic therapy with acetyl-DL-leucine compared to placebo on motor function measured by the Scale for the Assessment and Rating of Ataxia (SARA) in patients with CA. METHODS/DESIGN: An investigator-initiated, multicenter, European, randomized, double-blind, placebo-controlled, 2-treatment 2-period crossover phase III trial will be carried out. In total, 108 adult patients who meet the clinical criteria of CA of different etiologies (hereditary or non-hereditary, non-acquired) presenting with a SARA total score of at least 3 points will be randomly assigned in a 1:1 ratio to one of two different treatment sequences, either acetyl-DL-leucine (up to 5 g per day) followed by placebo or vice versa. Each sequence consists of two 6-week treatment periods, separated by a 4-week wash-out period. A follow-up examination is scheduled 4 weeks after the end of treatment. The primary efficacy outcome is the absolute change in the SARA total score. Secondary objectives are to demonstrate that acetyl-DL-leucine is effective in improving (1) motor function measured by the Spinocerebellar Ataxia Functional Index (SCAFI) and SARA subscore items and (2) QoL (EuroQoL 5 dimensions and 5 level version, EQ-5D-5 L), depression (Beck Depression Inventory, BDI-II) and fatigue (Fatigue Severity Score, FSS). Furthermore, the incidence of adverse events will be investigated. DISCUSSION: The results of this trial will inform whether symptomatic treatment with the modified amino-acid acetyl-DL-leucine is a worthy candidate for a new drug therapy to relieve ataxia symptoms and to improve patient care. If superiority of the experimental drug to placebo can be established it will also be re-purposing of an agent that has been previously used for the symptomatic treatment of dizziness. TRIAL REGISTRATION: The trial was prospectively registered at www.clinicaltrialsregister.eu (EudraCT no. 2015-000460-34) and at https://www.germanctr.de (DRKS-ID: DRKS00009733 )

Ablative efficiency of 532-nm laser vaporization compared to transurethral resection of the prostate: results from a prospective three-dimensional ultrasound volumetry study

Purpose: To assess and compare postoperative prostate volume changes following 532-nm laser vaporization (LV) and transurethral resection of the prostate (TURP). To investigate whether differences in volume reduction are associated with differences in clinical outcome. Methods: In this prospective, non-randomized study, 184 consecutive patients undergoing 120W LV (n=98) or TURP (n=86) were included. Transrectal three-dimensional ultrasound and planimetric volumetry of the prostate were performed preoperatively, after catheter removal, 6weeks, 6 and 12months. Additionally, clinical outcome parameters were recorded. Mann-Whitney U test and analysis of covariance were utilized for statistical analysis. Results: Postoperatively, a significant prostate volume reduction was detectable in both groups. However, the relative volume reduction was lower following LV (18.4 vs. 34.7%, p40ml. Re-operations were necessary in three patients following LV. Conclusions: The modest but significantly lower volume reduction following LV was associated with a lower PSA reduction, a lower Q max and more re-operations. Given the lack of long-term results after LV, our results are helpful for preoperative patient counseling. Patients with large prostates and no clear indication for the laser might not benefit from the procedure

ReSurveyGermany: Vegetation-plot time-series over the past hundred years in Germany

Vegetation-plot resurvey data are a main source of information on terrestrial biodiversity change, with records reaching back more than one century. Although more and more data from re-sampled plots have been published, there is not yet a comprehensive open-access dataset available for analysis. Here, we compiled and harmonised vegetation-plot resurvey data from Germany covering almost 100 years. We show the distribution of the plot data in space, time and across habitat types of the European Nature Information System (EUNIS). In addition, we include metadata on geographic location, plot size and vegetation structure. The data allow temporal biodiversity change to be assessed at the community scale, reaching back further into the past than most comparable data yet available. They also enable tracking changes in the incidence and distribution of individual species across Germany. In summary, the data come at a level of detail that holds promise for broadening our understanding of the mechanisms and drivers behind plant diversity change over the last century