Safety, Tolerability and Clinical Effects of a Rapid Dose Titration of Subcutaneous Treprostinil Therapy in Pulmonary Arterial Hypertension: A Prospective Multi-Centre Trial.

Background: Subcutaneous treprostinil has dose-dependent beneficial effects in patients with severe pulmonary arterial hypertension, but adverse effects like infusion site pain can lead to treatment discontinuation.

Objectives: The objective of this study was to evaluate safety, tolerability and clinical effects of a rapid up-titration dosing regimen of subcutaneous treprostinil using proactive infusion site pain management.

Methods: Effects of rapid up-titration dosing regimen on tolerability and clinical parameters were evaluated in this 16-week, open-label multi-centre study.

Applicability of cardiogoniometry as a non-invasive screening tool for the detection of graft vasculopathy in heart transplant recipients.

Currently available diagnostic modalities for the detection of graft vasculopathy following orthotopic heart transplantation are subject to various restrictions. We hypothesized that cardiogoniometry, a novel non-invasive diagnostic tool for the detection of atherosclerotic coronary vessel disease, is applicable in the graft vasculopathy setting. Cardiogoniometric results were obtained during routine follow-up in 49 consecutive, unselected heart transplant recipients and then retrospectively correlated blindly by an independent reader to recent angiographic findings.

Characteristics of service requests and service processes of fire and rescue service dispatch centers: analysis of real world data and the underlying probability distributions.

A sufficient staffing level in fire and rescue dispatch centers is crucial for saving lives. Therefore, it is important to estimate the expected workload properly. For this purpose, we analyzed whether a dispatch center can be considered as a call center.

Phenotypic and molecular characterization of clinically isolated Escherichia coli.

All diarrheagenic Escherichia coli carry at least one virulence-related property. Stool samples from 244 patients having acute or persistent diarrhea received after the exclusion of routine enteropathogens were investigated. Purely or predominantly isolated E.

Seven-point checklist for dermatoscopy: performance during 10 years of prospective surveillance of patients at increased melanoma risk.

Background: The retrospectively developed 7-point checklist is one of the most applicable dermatoscopic algorithms for clinical use. However, until today no prospective data on the diagnostic performance of this algorithm were reported.

Objective: Our aim was to assess the sensitivity, specificity, and diagnostic accuracy of the 7-point checklist in the setting of a prospective long-term study.

Analysis of putative miRNA binding sites and mRNA 3' ends as targets for siRNA-mediated gene knockdown.

Tremendous efforts have been made to develop short-interfering RNA (siRNA) design algorithms that generate highly functional siRNAs for gene knockdown. Nevertheless, "difficult-to-silence" target messenger RNAs (mRNAs) still exist for which no functionally validated siRNAs are available. MicroRNA (miRNA) sites in the mRNA 3'UTR, which interact with miRNA-loaded RNA-induced silencing complex (miRISC) for posttranscriptional gene regulation, provide alternative potentially accessible sites for siRNA.

Targeting gene delivery to activated vascular endothelium using anti E/P-Selectin antibody linked to PAMAM dendrimers.

Introduction: The adhesion molecules P- and E-selectin are expressed on activated endothelial cells, and are good targets for gene therapy aimed at inflammatory disease. We have therefore investigated the potential of targeting PAMAM dendrimers, a non viral vector system, to cells expressing P/E-selectin using a monoclonal antibody that recognises these molecules.

Materials And Methods: We used biotin and avidin to cross-link anti E/P-Selectin monoclonal antibody to pre-formed Superfect-DNA complexes that were then used to transfect reporter genes to CHO cells expressing E-Selectin, cytokine-activated primary Human Saphenous Vein Endothelial Cells (HSVEC) and whole vein segments.

Experimental study of hemodynamics in procedures to treat access-related ischemia.

Objective: This experimental study investigated the hemodynamic effect of corrective procedures for arteriovenous access-related ischemia in pulsatile flow.

Methods: Silicone models of an emulated tapered and bifurcated arterial tree of the upper arm and forearm were integrated into a pulsatile flow circuit. The model allowed the study of hemodynamics of simulated arteriovenous fistulas, including collateral circulation, as well as the study of different simulated procedures to improve distal hypoperfusion.

CD40 ligation during dendritic cell maturation reduces cell death and prevents interleukin-10-induced regression to macrophage-like monocytes.

Dendritic cells (DCs) have become popular candidates in cancer vaccination because of their crucial role in inducing T-cell responses. However, clinical studies greatly differ in their protocols for generating DCs and the efficacy in treating established tumors needs to be improved. We systematically analyzed DCs maturated by five different protocols for surface markers, the alloproliferative T-cell response, the DC survival after cytokine deprivation, the stability of surface markers under the influence of interleukin-10 (IL-10) and the DC cytokine secretion pattern.

A probability-based approach for the analysis of large-scale RNAi screens.

We describe a statistical analysis methodology designed to minimize the impact of off-target activities upon large-scale RNA interference (RNAi) screens in mammalian cells. Application of this approach enhances reconfirmation rates and facilitates the experimental validation of new gene activities through the probability-based identification of multiple distinct and active small interfering RNAs (siRNAs) targeting the same gene. We further extend this approach to establish that the optimal redundancy for efficacious RNAi collections is between 4-6 siRNAs per gene.

Insights into effective RNAi gained from large-scale siRNA validation screening.

Transfection of chemically synthesized short interfering RNAs (siRNAs) enables a high level of sequence-specific gene silencing. Although siRNA design algorithms have been improved in recent years, it is still necessary to prove the functionality of a given siRNA experimentally. We have functionally tested several thousand siRNAs for target genes from various gene families including kinases, phosphatases, and cancer-related genes (e.

Flow reduction in high-flow arteriovenous access using intraoperative flow monitoring.

Purpose: This study used intraoperative monitoring of the access flow to evaluate the results of flow reduction in the management of high-flow arteriovenous access-related symptoms of distal ischemia and cardiac insufficiency.

Methods: A retrospective study was conducted of 95 patients (78 with ischemia, 17 with cardiac failure) who underwent flow reduction between 1999 and 2005. A preoperatively measured access flow-volume rate > 800 mL/min for autogenous accesses (n = 77) and > 1200 mL/min for prosthetic accesses (n = 18) was the selection criterion for the use of a flow reduction procedure.

Results from an observational trial: digital epiluminescence microscopy follow-up of atypical nevi increases the sensitivity and the chance of success of conventional dermoscopy in detecting melanoma.

We analyzed the value of digital epiluminescence microscopy (DELM) for the long-term follow-up of atypical nevi. Patients (n=530) were prospectively categorized into defined melanoma risk groups and followed by clinical and epiluminescence microscopy (ELM) examinations. Atypical nevi (n=7001) were additionally followed by DELM.

Late enhancement: a new feature in MRI of arrhythmogenic right ventricular cardiomyopathy?

Aim of the study was to evaluate whether late enhancement (LE) in contrast-enhanced MRI can be used to characterize fibrofatty myocardial replacement in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC). Fifteen patients with suspected ARVC underwent CE-MRI using a 1.5 T scanner.

Assessment of 3 xeroderma pigmentosum group C gene polymorphisms and risk of cutaneous melanoma: a case-control study.

Individuals with the rare DNA repair deficiency syndrome xeroderma pigmentosum (XP) are sensitive to the sun and exhibit a 1000-fold increased risk for developing skin cancers, including cutaneous melanoma. Inherited polymorphisms of XP genes may contribute to subtle variations in DNA repair capacity and genetic susceptibility to melanoma. We investigated the role of three polymorphic alleles of the DNA repair gene XPC in a hospital-based case-control study of 294 Caucasian patients from Germany who had cutaneous melanoma and 375 healthy cancer-free sex-matched Caucasian control subjects from the same area.

No association between three xeroderma pigmentosum group C and one group G gene polymorphisms and risk of cutaneous melanoma.

Xeroderma pigmentosum (XP) patients exhibit a 1000-fold increased risk for developing skin cancers including malignant melanoma. We investigated the role of three variant alleles of the DNA repair gene XPC and one variant allele of the XPG gene in a hospital-based case-control study of 294 Caucasian patients from Germany with malignant melanoma and 375 healthy control individuals from the same area matched by sex. The polymorphisms G1580A (XPC exon 8; Arg492His), T1601C (XPC exon 8; Val499Ala), G2166A (XPC exon 10; Arg687Arg), and C3507G (XPG exon 15; Asp1104His) were not in linkage disequilibrium.

Effect of tapered grafts on hemodynamics and flow rate in dialysis access grafts.

Aim: Aside from the high incidence of venous stenosis, high-output failure and peripheral steal syndromes remain serious problems of vascular access. Meanwhile commercial tapered grafts are available to address this topic, but little is known about its effect neither on graft flow nor on hemodynamics.

Methods: Anastomotic models were constructed using a clear silicon elastomer.

Monoclonal rearrangement of the T cell receptor gamma-chain in lichenoid pigmented purpuric dermatitis of gougerot-blum responding to topical corticosteroid therapy.

Lichenoid pigmented purpuric dermatitis of Gougerot-Blum belongs to a group of closely related disorders which are termed pigmented purpuric dermatoses. It clinically manifests itself with grouped lichenoid papules in association with purpuric lesions. We report a case of lichenoid pigmented purpuric dermatitis of Gougerot-Blum with a heavy band-like CD4-positive lymphocytic infiltrate and clonal rearrangements of the gamma-chain of the T cell receptors as detected by polymerase chain reaction/denaturing gradient gel electrophoresis.

Computational fluid dynamics and vascular access.

Anastomotic intimal hyperplasia caused by unphysiological hemodynamics is generally accepted as a reason for dialysis access graft occlusion. Optimizing the venous anastomosis can improve the patency rate of arteriovenous grafts. The purpose of this study was to examine, evaluate, and characterize the local hemodynamics and, in particular, the wall shear stresses in conventional venous end-to-side anastomosis and in patch form anastomosis (Venaflo) by three-dimensional computational fluid dynamics (CFD).

Orthotopic transplantation model of human gastrointestinal cancer and detection of micrometastases.

Aim: To establish a relevant animal model of human gastrointestinal cancer, which can be used for repetitive investigations, so as to improve our understanding and management of carcinogenesis and cancer metastasis.

Methods: Intact tissues of human colorectal and pancreatic cancers were transplanted in nude mice. The biological characteristics of the original and the corresponding transplanted tumors were investigated by HE staining, PAS staining and immunostaining.

Effect of intravenous iloprost and alprostadil (PGE1) on peripheral resistance during femoro-distal reconstructions.

Background: A prospective, randomised study was undertaken to investigate the effect of intravenous infusion of either iloprost, the stable prostacyclin (PGI2) analogue, or alprostadil (prostaglandin E1) on peripheral resistance (PR) during femoro-distal reconstruction.

Methods: A prospective randomised study was performed with 35 patients. The PR Measurement of peripheral resistance involved a silicon tube temporarily inserted between the donor and recipient vessel.

Comparison of Two Different Arteriovenous Anastomotic Forms By Numerical 3D Simulation of Blood Flow.

Anastomotic intimal hyperplasia caused by unphysiological hemodynamics is generally accepted as a reason for dialysis access graft occlusion. Optimizing the venous anastomosis can improve the patency rate of arteriovenous grafts. The purpose of this study was to examine, evaluate and characterize the local hemodynamics, and in particular, wall shear stresses in conventional venous end-to-side anastomosis and in patch form anastomosis (Venaflotrade mark) by Computational Fluid Dynamics (CFD).

Isolated tumor cells are frequently detectable in the peritoneal cavity of gastric and colorectal cancer patients and serve as a new prognostic marker.

Objective: To evaluate the prognostic significance of isolated tumor cells detected by a panel of various monoclonal antibodies.

Summary Background Data: Previously, we showed by using immunocytology that cancer cells are frequently found in bone marrow and peritoneal cavity samples of gastrointestinal cancer patients.

Methods: Findings in bone marrow and peritoneal cavity samples were compared and correlated with the 4-year survival rate of 84 gastric and 109 colorectal patients with cancer.

Crystal structure of the two RNA binding domains of human hnRNP A1 at 1.75 A resolution.

Heterogeneous ribonucleoprotein A1 (hnRNP A1) is an abundant eukaryotic nuclear RNA binding protein. A1 is involved in the packaging of pre-mRNA into hnRNP particles, transport of poly A+ mRNA from the nucleus to the cytoplasm and may modulate splice site selection. The crystal structure of A1(RBD1,2) reveals two independently-folded RNA binding domains (RBDs) connected by a flexible linker.