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Budapest, Hungary

Papp M.,Debrecen University | Lakatos P.L.,Semmelweis University | Harsfalvi J.,Debrecen University | Farkas G.,Debrecen University | And 12 more authors.
Human Immunology | Year: 2010

Mannose-binding lectin (MBL) is a major, soluble, pattern-recognition molecule and an important component of the innate host defense. The role of MBL in inflammatory bowel diseases (IBDs) is controversial. We determined the prevalence of MBL deficiency in a Hungarian IBD patients' cohort, and whether it is associated with the antimicrobial antibody formation or particular clinical manifestations. Nine hundred ninety IBD patients and 225 healthy subjects were investigated. Sera were assayed for MBL and a panel of antimicrobial antibodies (anti-OMP, anti-Saccharomyces cerevisiae antibodies, and antiglycans) by ELISA. TLR4 and NOD2/CARD15 variants were tested by polymerase chain reaction/restriction fragment length polymorphism. Median MBL level was not significantly different between IBDs (Crohn's disease [CD]: 929; ulcerative colitis [UC]: 810 ng/ml) and the control group (1027 ng/ml), as well as the prevalence of absolute MBL deficiency (<100 ng/ml) (CD: 15.0%, UC: 18.4%, controls: 15.6%). The presence of a low MBL level (<500 ng/ml) was not associated with any of the examined serologic markers, or their combinations. In addition, there was no association with the clinical presentation, disease course, or response to treatment. TLR4 variant genotype was more common in CD patients without MBL deficiency (11% vs. 1.7%, OR: 7.29, 95% CI: 1.08-53.9, p = 0.02). We failed to confirm any association between MBL deficiency and serologic marker positivity. MBL deficiency was not predictive for clinical phenotype or disease activity in IBDs. © 2010 American Society for Histocompatibility and Immunogenetics.

Norgaard K.,Hvidovre University Hospital | Scaramuzza A.,Luigi Sacco Hospital | Bratina N.,University of Ljubljana | Lalic N.M.,University of Belgrade | And 7 more authors.
Diabetes Technology and Therapeutics | Year: 2013

Background: Sensor-augmented pump (SAP) therapy can improve glycemic control, compared with multiple daily insulin injections or with insulin pump therapy alone, without increasing the risk of hypoglycemia. Subjects and Methods: A 12-month observational study in patients with type 1 diabetes treated with continuous subcutaneous insulin infusion (CSII), upon the introduction of continuous glucose monitoring (CGM), was conducted in 15 countries (in Europe and in Israel) to document the real-life use of SAP and assess which variables are associated with improvement in type 1 diabetes management. Results: Data from 263 patients (38% male; mean age, 28.0±15.7 years [range, 1-69 years]; body mass index, 23.3±4.9 kg/m2; diabetes duration, 13.9±10.7 years; CSII duration, 2.6±3 years) were collected. Baseline mean glycated hemoglobin A1c (HbA1c) was 8.1±1.4%; 82% had suboptimal HbA1c (≥7%). The average sensor use for 12 months was 30% (range, 0-94%), and sensor use decreased with time (first 3 months, 37%; last 3 months, 27%). Factors associated with improvement in HbA1c after 12 months in patients with baseline HbA1c ≥7% were high baseline HbA1c (P<0.001), older age group (P<0.001), and more frequent sensor use (P=0.047). Significantly less hospitalization, increased treatment satisfaction, and reduced fear of hypoglycemia were reported after 12 months of SAP. Conclusions: This is the largest and longest multicenter prospective observational study providing real-life data on SAP. These results are consistent with those of controlled trials showing the effectiveness of CGM in pump users. © Mary Ann Liebert, Inc.

Bene L.,Peterfy Hospital | Falus A.,Semmelweis University | Falus A.,Hungarian Academy of Sciences | Baffy N.,Semmelweis University | Fulop A.K.,Semmelweis University
Pathology and Oncology Research | Year: 2011

The factors involved in the pathogenesis of Crohn's disease and ulcerative colitis, the two major types of inflammatory bowel disease (IBD) are summarized. Intestinal antigens composed of bacterial flora along with antigen presentation and impaired mucosal barrier have an important role in the initiation of IBD. The bacterial community may be modified by the use of antibiotics and probiotics. The dentritic cells recognize the antigens by cell surface Toll like receptor and the cytoplasmic CARD/NOD system. The balance between Th1/Th2/Th17 cell populations being the source of a variety of cytokines regulates the inflammatory mechanisms and the clearance of microbes. The intracellular killing and digestion, including autophagy, are important in the protection against microbes and their toxins. The homing process determines the location and distribution of the immune cells along the gut. All these players are potential targets of pharmacological manipulation of disease status. © 2011 Arányi Lajos Foundation.

Ronaszki A.,Peterfy Hospital | Alings M.,Amphia Ziekenhuis Cardiologie | Egstrup K.,Forsknings Og Udviklingsafdeling | Gaciong Z.,Katedra i Klinika ChorobWewnetrznych i Nadcisnienia Tetniczego i Angiologii | And 9 more authors.
Europace | Year: 2011

Aim: AZD1305 is a combined ion channel blocker developed for the treatment of atrial fibrillation (AF). The aim of this study was to determine whether AZD1305 was effective in converting AF to sinus rhythm (SR). Methods and results: Patients with AF episodes of duration 3 h to 3 months were randomized in a 3:1 ratio to receive a maximum 30 min intravenous infusion of AZD1305 or matching placebo. The primary efficacy endpoint was the proportion of patients converting within 90 min of the start of infusion, after which patients who had not converted were to undergo direct current (DC) cardioversion. Four ascending AZD1305 dose groups were assigned sequentially, with dose rates of 50, 100, 130, and 180 mg/h.A total of 171 patients were randomized. Pharmacological conversion was achieved in 0 of 43 patients (0) in the placebo group, and in 2 of 26 (8; P 0.14 vs. placebo), 8 of 45 (18; P=0.006), 17 of 45 (38; P< 0.001), and 6 of 12 patients (50; P< 0.001) in AZD1305 dose groups 14, respectively. Maximum QTcF (QT interval corrected according to Fridericias formula) generally increased dose-dependently up to a plateau, although there was wide variation between patients. Two patients experienced torsade de pointes (TdP): one patient without symptoms in dose group 3, and one patient requiring DC defibrillation in dose group 4. Both patients recovered without sequelae. Conclusions: AZD1305 was effective in converting AF to SR, but was associated with QT prolongation and TdP. The benefitrisk profile was judged as unfavourable and the AZD1305 development programme was discontinued.Clinical trial registration: http://clinicaltrials.gov identifier NCT00915356. © 2011 The Author.

Ivanyi T.,Eli Lilly and Company | Fovenyi J.,Peterfy Hospital | Faludi P.,Uzsoki Hospital | Han J.,Amylin Pharmaceuticals Inc. | And 3 more authors.
Clinical Therapeutics | Year: 2012

Background: Studies of the glucagon-like peptide-1 receptor agonists (GLP-1RAs) are needed to determine the durability of metabolic response and tolerability associated with long-term treatment. Objective: The present study was conducted to provide long-term data on glycemic control, weight changes, and tolerability of exenatide 10 μg BID treatment in patients with type 2 diabetes mellitus who have failed to achieve glycemic targets with oral antihyperglycemic medication. Methods: In this uncontrolled, open-label trial with treatment up to 156 weeks, patients received exenatide 10 μg BID while continuing treatment with metformin and/or a sulfonylurea (SFU). Intent-to-treat (ITT), 52-, 100-, and 132-week completer populations were defined. Metabolic changes were analyzed in the completer and ITT populations; adverse events (AEs) were summarized in the ITT population. Descriptive statistics were used for absolute and change-from-baseline data. Within-treatment comparisons were conducted using the paired t test. Results: Of 155 patients in the ITT population (mean [SD]: age, 59 [9] years; 56% female; duration of diabetes, 9.1 [5.9] years; weight, 88.8 [16.5] kg; body mass index, 31.9 [4.7] kg/m 2; hemoglobin [Hb] A 1c, 8.7% [1.2%]), 133, 111, and 103 patients completed 52, 100, and 132 weeks of treatment, respectively. In the ITT population, the mean (SE) change in HbA 1c from baseline to week 132 was -1.0% (0.10%) (P < 0.0001). In patients completing 52, 100, and 132 weeks, HbA 1c changes from baseline to end point were -1.3% (0.10%), -1.0% (0.12%), and -1.0 (0.13%) (P < 0.0001), with 40% of patients achieving HbA 1c <7% at 132 weeks. Patients in the ITT and completer populations experienced mean (SE) weight changes of -3.7 (0.39) kg and -3.9 (0.51) kg (P < 0.0001) at week 132. Improved glycemic control and weight loss occurred in 63% of patients in the completer population at week 132. In addition, 38% of completers at week 132 achieved HbA 1c <7% without weight gain. No relationship was found between the development of antiexenatide antibodies and change in HbA 1c. The most common AEs were gastrointestinal in nature, reported in 46% of patients and leading to discontinuation in 7 cases. Serious AEs were reported in 26% of patients, and 18% withdrew due to a treatment-emergent AE. Of 24% of patients in whom hypoglycemia was reported, 22% were on SFU or metformin + SFU combination, and 2% were on metformin. Conclusions: The findings from this open-label, single-arm study characterized the response to exenatide 10 μg BID for up to 132 weeks. Significant, persistent improvements in HbA 1c and weight were observed in patients receiving exenatide BID, with reported AEs consistent with those from studies of shorter duration. © 2012 Elsevier HS Journals, Inc.

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