[S2k-guideline Helicobacter pylori and gastroduodenal ulcer disease]. / S2k-Leitlinie Helicobacter pylori und gastroduodenale Ulkuskrankheit.

In the line "bismuth-containing quadruple therapy" of Table 7 (p 342), in the column "dosage" incorrectly at the three antibiotics respectively 1-1-1-1. The correct is: 3-3-3-3.

Left ventricular mass and oxygen uptake in top handball athletes.

The key challenge in athlete's screening is the distinction between abnormal and normal which is hindered by the fact that the adaptation to sports activity in endurance athletes is different to that in power athletes. Especially cardiomyopathies provoke changes in ECG and echocardiography (echo) at an early stage when clinical symptoms are absent. ECG and echo data and their relationship to fitness peculiar to top handball players have never been described. We studied 291 male first league handball players (32 Olympians/47 national players) (25.3±4.4 years). Check up consisted of ECG, spiroergometry and echocardiography. None had T-wave inversions, 3.1% showed early repolarisation abnormalities in the precordial leads. Sokolow-Lyon voltage criterion for left ventricular hypertrophy was positive in 19.3%. Spiroergometry showed a maximum oxygen uptake (peakVO2) of 50.3±7.7 ml/min/kg body weight. LVmass was increased in comparison to normal values. There was a correlation between peakVO2 and LVindex (p<0.001, r=0.341), (LVmass/peak VO2 p=0.053, r=0.125). A relationship between cardiac dimensions and peakVO2 could not be confirmed. In professional handball players early repolarisation abnormalities were less frequent and LVmass was increased when compared with soccer players. The need for normal values for different types of sports is crucial to guarantee a proper evaluation of athletes.

[The "asymptomatic" patient with chronic acquired heart valve disease]. / Der "asymptomatische" Patient mit chronischem Herzklappenfehler.

An intervention for chronic acquired valvular heart disease may either be indicated in symptomatic patients to relieve symptoms and improve quality of life or in asymptomatic patients to improve long-term prognosis, e.g., by preventing disease-related complications like chronic heart failure or arrhythmias. For proper action according to current guidelines, the systematic evaluation of symptoms related to the underlying valve disease is of utmost importance. If a discrepancy between symptoms reported or not reported by the patients and the severity of the valve disease is supposed, true absence of symptoms and exercise tolerance should be verified by spiroergometry. In the truly asymptomatic patient with a severe valvular lesion, preservation of myocardial adaption to the chronic volume or pressure overload should be tested utilizing appropriate imaging techniques like radionuclide ventriculography under exercise conditions. The proper evaluation of the functional status is of growing importance in our aging population with its sedentary lifestyle. In this context, the results of a survey should be kept in mind, which indicated that a significant proportion of patients still have interventions too late during the natural history of their valve disease with symptoms of congestive heart failure, arrhythmias, and the risk of sudden cardiac death persisting after a primarily successful valve repair or replacement.

[74-year-old patient with cystic pancreatic lesions. An endoscopy-based algorithm]. / 74-jähriger Patient mit zystischen Pankreasraumforderungen. Vorschlag für einen endoskopischen Diagnosealgorithmus.

Often, equivocal pancreatic cystic masses in a patient cannot be clearly identified. We report on a 74-year-old patient who consulted us with size-gaining multi-cystic lesions located at the pancreatic head and tail as well as with an increased CA 19-9 level. By using diagnostic methods as ultrasound, radiological images and innovative endoscopic techniques an intraductal papillary mucinous neoplasm (IPMN) was diagnosed. Evaluation of equivocal cystic lesions requires developing of further strategies as well as integration of new concepts: We present a diagnostic algorithm based on endoscopy that enables us to perform an adapted therapy by having a more accurate evaluation and the opportunity to gain samples where unclear lesions are given.

Adaptive servoventilation in diastolic heart failure and Cheyne-Stokes respiration.

A high prevalence of nocturnal Cheyne-Stokes respiration (CSR) has been documented in patients with heart failure with normal left ventricular ejection fraction (HFNEF). The aim of the present study was to investigate the effects of adaptive servoventilation (ASV) for treatment of CSR in these patients. In 60 patients with HFNEF, defined according to current European Society of Cardiology guidelines, CSR was documented by polysomnography (apnoea/hypopnoea index (AHI) of >15 events x h(-1)). ASV treatment was offered to all patients; 21 initially rejected treatment, withdrew from treatment or presented noncompliant during follow-up (controls), whereas ongoing ASV therapy was initiated in 39 patients (ASV group). Echocardiography, cardiopulmonary exercise testing and measurement of N-terminal-pro-brain natriuretic peptide were performed at baseline and follow-up (11.6+/-3 months). ASV therapy led to a significant reduction in AHI, longest apnoea and hypopnoea length, maximum and mean oxygen desaturation by pulse oximetry, percentage of study time with an oxygen saturation of <90% and arousal index. In addition, significant positive effects could be confirmed on absolute and predicted peak oxygen consumption, oxygen consumption at the individual aerobic-anaerobic threshold, oxygen pulse, as well as left atrial size, and transmitral flow patterns (mean early diastolic lengthening velocity and the ratio of peak early Doppler mitral inflow velocity to this lengthening velocity). ASV effectively attenuates CSR in patients with HFNEF and improves heart failure symptoms and cardiac function. Whether or not this is accompanied by an improved prognosis remains to be determined.

Infected necrosis in severe pancreatitis--combined nonsurgical multi-drainage with directed transabdominal high-volume lavage in critically ill patients.

BACKGROUND: Infection of pancreatic necrosis is a life-threatening complication during the course of acute pancreatitis. In critically ill patients, surgical or extended endoscopic interventions are associated with high morbidity and mortality. Minimally invasive procedures on the other hand are often insufficient in patients suffering from large necrotic areas containing solid or purulent material. We present a strategy combining percutaneous and transgastric drainage with continuous high-volume lavage for treatment of extended necroses and liquid collections in a series of patients with severe acute pancreatitis. PATIENTS AND METHODS: Seven consecutive patients with severe acute pancreatitis and large confluent infected pancreatic necrosis were enrolled. In all cases, the first therapeutic procedure was placement of a CT-guided drainage catheter into the fluid collection surrounding peripancreatic necrosis. Thereafter, a second endosonographically guided drainage was inserted via the gastric or the duodenal wall. After communication between the separate drains had been proven, an external to internal directed high-volume lavage with a daily volume of 500 ml up to 2,000 ml was started. RESULTS: In all patients, pancreatic necrosis/liquid collections could be resolved completely by the presented regime. No patient died in the course of our study. After initiation of the directed high-volume lavage, there was a significant clinical improvement in all patients. Double drainage was performed for a median of 101 days, high-volume lavage for a median of 41 days. Several endoscopic interventions for stent replacement were required (median 8). Complications such as bleeding or perforation could be managed endoscopically, and no subsequent surgical therapy was necessary. All patients could be dismissed from the hospital after a median duration of 78 days. CONCLUSION: This approach of combined percutaneous/endoscopic drainage with high-volume lavage shows promising results in critically ill patients with extended infected pancreatic necrosis and high risk of surgical intervention. Neither surgical nor endoscopic necrosectomy was necessary in any of our patients.

Long-term follow-up of percutaneous transhepatic biliary drainage (PTBD) in patients with benign bilioenterostomy stricture.

BACKGROUND AND AIMS: Anastomotic strictures are well-known complications after bilioenterostomy. Endoscopic procedures are usually not possible in patients with a bilioenterostomy. Hence, percutaneous transhepatic biliary drainage (PTBD) has become the treatment of choice for the management of these patients. The main goal of the present study was to analyze the long-term follow-up of PTBD in such patients. METHODS AND PATIENTS: Between January 1996 and December 2006, 44 patients with benign anastomotic stricture after bilioenterostomy were identified by an analysis of the PTBD database, hospital charts, and cholangiograms. RESULTS: In 27/44 patients the percutaneous transhepatic biliary drain was successfully removed after 19.9 +/- 16.1 months (treatment success in 61.4 %). During a mean follow-up of 53.7 +/- 28.4 months after removal of the drain, no evidence was found of recurrent strictures in these patients. Ten out of 44 patients carry permanent drains (22.6 % of patients with ongoing treatment, mean follow-up 46.4 +/- 54.7 months) without the option for further surgery owing to concomitant disease (n = 2) or because they refused further surgery (n = 8). In 7 out of 44 patients (16 %) PTBD treatment was deemed to have failed and the patients underwent repeat operation. CONCLUSIONS: PTBD should be considered the treatment of choice in patients with benign anastomotic stricture after bilioenterostomy, especially after stricturing of a hepatojejunostomy.

S3-guideline "helicobacter pylori and gastroduodenal ulcer disease" of the German society for digestive and metabolic diseases (DGVS) in cooperation with the German society for hygiene and microbiology, society for pediatric gastroenterology and nutrition e. V., German society for rheumatology, AWMF-registration-no. 021 / 001.

This guideline updates a prior consensus recommendation of the German Society for Digestive and Metabolic Diseases (DGVS) from 1996. It was developed by an interdisciplinary cooperation with representatives of the German Society for Hygiene and Microbiology, the Society for Pediatric Gastroenterology and Nutrition (GPGE), and the German Society for Rheumatology. The guideline is methodologically based on recommendations of the Association of the Scientific Medical Societies in Germany (AWMF) for providing a systematic evidence-based S 3 level consensus guideline and has also implemented grading criteria according to the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) process. Clinical applicability of study results as well as specifics for Germany in terms of epidemiology, antibiotic resistance status, diagnostics, and therapy were taken into account.

[Endosonography for differential diagnosis of malignant findings of the pancreas]. / Endoskopischer Ultraschall zur Differenzialdiagnose maligner Befunde des Pankreas.

Due to recent technical innovations endosonography has attained a special importance for the examination of malignant pancreatic tumors. Modern high-resolution radial instruments with 360 degrees imaging give a very good overall view with fine resolution and contrast and allow excellent detection of solid space-occupying lesions in the region of the pancreas. In meta-analyses a very good sensitivity for tumor detection of over 90% could be demonstrated, comparable to the results of the modern CT pancreas spiral technique. Endosonography has an advantage over CT examination especially for the diagnostics of very small neuroendocrine tumors (<1 cm), for example for the detection of insulinomas. For cystic pancreas processes only endosonography allows further specific differential diagnostics by the determination of important prognostic tumor markers, such as CEA or CA-19-9 by simultaneous puncture of the lesion.

A novel and practicable ERCP training system with simulated fluoroscopy.

INTRODUCTION: Simulators facilitate the acquisition of technical skills for endoscopy. Here, we describe the development, introduction, and first evaluation of a novel generation of mechanical endoscopic retrograde cholangiopancreatography (ERCP) simulation models with simulated fluoroscopy, the X-Vision ERCP Training System. METHODS: A custom-made modular ERCP simulation system was built with the use of universally obtainable materials and tools. The trainee controls ERCP activities on two screens: the aspect of the papilla and duodenum is shown on the conventional endoscopy monitor, and the trainee's actions in the equivalents of the pancreaticobiliary ducts are shown on the viewing screen of the model. Thereby, the latter screen serves as a substitute for fluoroscopy. Currently, four different models are available, allowing simulation of selective cannulation of the pancreatic or bile duct, intubation of differently arranged papillae, stent placement, and sphincterotomy of a biopapilla. The X-Vision ERCP Training System was first used during an ERCP course attended by 26 endoscopists. Trainees were supervised by an ERCP expert and an experienced ERCP nurse at each training model. The training system was evaluated by the participants and experts using a specific questionnaire. RESULTS: During the course there were no technical problems related to the X-Vision ERCP Training System. After sphincterotomy the organic papillae could easily be exchanged within less than 15 seconds. Overall, the X-Vision ERCP Training System achieved favorable results in all categories assessed. CONCLUSION: The new X-Vision ERCP Training System is simple and effective. A first evaluation in the context of an ERCP course showed impressive results.

Do we need gastric acid?

Evidence from comparative anatomy and physiology studies indicates that gastric acid secretion developed during the evolution of vertebrates approximately 350 million years ago. The cellular mechanisms that produce gastric acid have been conserved over the millennia and therefore proton pump inhibitors have pharmacological effects in almost all relevant species. These observations suggest that gastric acid provides an important selective advantage; however, in modern-day humans the need for gastric acid can be questioned in light of the widespread use of safe and effective pharmacologic acid suppression. The Kandahar Working Group addressed questions concerning the need, production and effects of gastric acid, specifically: (1) motility in the upper gastrointestinal (GI) tract; (2) neuroendocrine factors; (3) digestive and mucosal processes; (4) microbiology, and (5) central processes and psychological involvement. We addressed each topic with the individual models available to answer our questions including animal versus human studies, pharmacologic, surgical as well as pathophysiologic states of acid suppression.

Direct comparison between in vivo and in vitro microsized particle phagocytosis assays in Drosophila melanogaster.

The effects of micro and nanoparticles on the innate immune system have been widely investigated and a general lack of agreement between in vivo and in vitro assays has been observed. In order to determine the origin of these discrepancies, there is a need for comparing the results of in vivo and in vitro phagocytosis assays obtained using the same particles and same immune cells. Here, we establish an in vivo polystyrene microsized particle phagocytosis assay in Drosophila melanogaster and compare it with an in vitro assay consisting of exposing the same immune cells in culture to the same particles. The distribution of number of phagocytized beads per cell was shifted to lower numbers of beads per cell in the case of the in vitro assay compared to the in vivo assay, which we suggest is partly due to a reduced amount of membrane available in cultured cells.

The effect of sedation on the quality of upper gastrointestinal endoscopy: an investigator-blinded, randomized study comparing propofol with midazolam.

BACKGROUND AND STUDY AIMS: Sedation with propofol is associated with a high acceptance rate in upper gastrointestinal endoscopy. So far, however, there are no valid data on whether the use of propofol can increase the general quality of the endoscopic examination. PATIENTS AND METHODS: A total of 60 patients referred for upper gastrointestinal endoscopy were randomized to receive sedation with either midazolam (n = 30) or propofol (n = 30). The maximum dosages permitted were 5 mg of midazolam and 500 mg of propofol. The examinations were recorded on videotapes, and the quality of upper endoscopy was assessed by videotape analysis by three experienced endoscopists who were all blinded to patient data and the medications used for sedation. A score sheet was used with 18 assessment items that each represented a step of upper gastrointestinal endoscopy and a global score for the entire examination. A scale ranging from 1 (excellent) to 6 (very poor) was used. Data were analyzed on an intention-to-investigate basis: inability to perform the procedure because of a patient's intolerance of the procedure, for example, was scored as 6 (i. e. very poor). RESULTS: Patients in the two groups were well matched with respect to demographic and clinical data. Four patients in the midazolam group could not be adequately examined. The median dosage used for sedation was 5 mg midazolam (range 2-5 mg) and 160 mg propofol (range 70-320 mg). When assessments by all three blinded examiners were added together, propofol sedation was found to result in significantly better scores for all parameters except for the assessments of "Z-line/cardia", "duodenal bulb", and "duodenal folds" (all P < 0.05, Mann-Whitney U test). CONCLUSION: Sedation with propofol might increase the quality of upper endoscopy. This finding may have a significant impact on the selection of the type of sedation, not only in terms of increasing patients' acceptance of the procedure, but also for improving the diagnostic accuracy of upper gastrointestinal endoscopy.

Targeting transcription-coupled nucleotide excision repair overcomes resistance in chronic lymphocytic leukemia.

Treatment resistance becomes a challenge at some point in the course of most patients with chronic lymphocytic leukemia (CLL). This applies to fludarabine-based regimens, and is also an increasing concern in the era of more targeted therapies. As cells with low-replicative activity rely on repair that triggers checkpoint-independent noncanonical pathways, we reasoned that targeting the nucleotide excision repair (NER) reaction addresses a vulnerability of CLL and might even synergize with fludarabine, which blocks the NER gap-filling step. We interrogated here especially the replication-independent transcription-coupled-NER ((TC)-NER) in prospective trial patients, primary CLL cultures, cell lines and mice. We screen selected (TC)-NER-targeting compounds as experimental (illudins) or clinically approved (trabectedin) drugs. They inflict transcription-stalling DNA lesions requiring TC-NER either for their removal (illudins) or for generation of lethal strand breaks (trabectedin). Genetically defined systems of NER deficiency confirmed their specificity. They selectively and efficiently induced cell death in CLL, irrespective of high-risk cytogenetics, IGHV status or clinical treatment history, including resistance. The substances induced ATM/p53-independent apoptosis and showed marked synergisms with fludarabine. Trabectedin additionally perturbed stromal-cell protection and showed encouraging antileukemic profiles even in aggressive and transforming murine CLL. This proof-of-principle study established (TC)-NER as a mechanism to be further exploited to resensitize CLL cells.

Key importance of the Helicobacter pylori adherence factor blood group antigen binding adhesin during chronic gastric inflammation.

Helicobacter pylori has been assigned as a class I carcinogen because of its relation to gastric adenocarcinoma. Chronic H. pylori infection may lead to severe gastritis, glandular atrophy (AT), and intestinal metaplasia (IM). Strains secreting the vacuolating toxin VacA and producing the cytotoxin-associated antigen CagA (type 1 strains), as well as the blood group antigen binding adhesin (BabA) targeting Lewis(b) antigens, have been associated previously with distal gastric adenocarcinoma (M. Gerhard et al., Proc. Natl. Acad. Sci. USA, 96: 12778-12783, 1999) and may therefore also be related to lesions preceding gastric cancer. Antral and corpus biopsies were collected from 451 patients; 151 were H. pylori positive, as determined by PCR. Gastric biopsies were histologically evaluated for activity of gastritis (G0-G3, granulocyte infiltration), chronicity of gastritis (L1-L3, lymphocyte infiltration), and the presence of IM and/or AT according to the Sydney classification. Simultaneously, the presence of bacterial genes encoding virulence and adherence factors (racAs1/s2, cagA, and babA2) was determined by PCR. The presence of cagA+ and vacAs1 (alone or combined) both correlated with activity and chronicity of gastritis (P < 0.05); however, the overall prevalence of these genes was 60 or 72%, respectively, and was thus relatively frequent. The babA2 gene, encoding the adhesin BabA, was detected in 38% of infected patients and was correlated with the activity of gastritis in antrum and corpus (P < 0.005). cagA+/vacAs1+ strains (suggesting the presence of type 1 strains) that were also babA2 positive were detected more frequently in patients with severe histological alterations (such as G3, IM, or AT) compared with subjects without these changes (P < 0.01). cagA+/vacAs1+ strains that were babA2 negative, however, lacked a significant correlation with severe histological changes, activity, or chronicity of gastritis in antrum and corpus. Adherence of H. pylori via BabA appears to be of importance for efficient delivery of VacA and CagA and may play a special role in the pathogenesis of severe histological changes.

Short-term effects and adverse events of endoscopically applied radiofrequency ablation appear to be comparable with photodynamic therapy in hilar cholangiocarcinoma.

BACKGROUND AND STUDY AIMS: Radiofrequency ablation (RFA) is a new endoscopic palliation therapy for malignant biliary obstruction. The aim of this study was to compare the short-term effects of biliary drainage and adverse events of this technique with the standard of endoscopical treatment of hilar cholangiocarcinoma, photodynamic therapy (PDT). PATIENTS AND METHODS: We retrospectively and since December 2012 prospectively investigated the efficacy and adverse events of RFA in patients with hilar cholangiocarcinoma in two tertiary referral centers between November 2011 and January 2013. The approach of the study was prospective, but because of the large amount of retrospectively included patients, the design of the study is overall retrospective. A group of 20 patients treated with PDT between April 2005 and May 2011 served as a historical control. RESULTS: Fourteen patients received 31 biliary RFAs and 20 patients received 36 PDTs. Within the RFA group, a significant decrease (p = 0.046) of the bilirubin level was seen 14 days after the first RFA (3.3 ± 3.9 (mg/dl) versus 2.3 ± 2.6 (mg/dl)). In the PDT group no significant decrease (p = 0.67) of the bilirubin level was obtained (4.1 ± 6.9 (mg/dl) versus 3.5 ± 5.3 (mg/dl)). In the PDT group (13/20, 65%) a significantly higher number of premature stent replacements (<3 months) after the first intervention was noticed in comparison with the RFA group (four of 14, 29%) (p < 0.01). Between the first and fifth procedure, post-interventional adverse events tend to occur more frequently in patients with PDT (eight of 20, 40%) than with RFA (three of 14, 21%) (p = 0.277). CONCLUSIONS: Looking at the short-term effects, we conclude that RFA may present a therapeutic alternative to PDT for palliative treatment of malignant biliary obstruction because of its simple feasibility and moderate adverse event rate. To provide a definitive evaluation of the long-term effects and of overall median survival, a controlled trial with PDT must follow.

Cloning and expression of the rabbit gastric CCK-A receptor.

Cholecystokinin stimulates pancreatic zymogen secretion by binding with high affinity to a receptor on the pancreatic acinar cell. This receptor has been cloned and shown to be a CCK-A subtype. CCK also stimulates pepsinogen secretion from the gastric chief cell with high affinity. Using polymerase chain reaction with primers from the known sequence of the rat pancreatic CCK-A receptor cDNA, we prepared a 600 bp product from rat and rabbit stomach cDNA. From Southern analysis these represented a fragment of a gastric CCK-A receptor. PCR was then used to amplify a rabbit lambda ZAP II gastric epithelial cDNA library with the same primers, and the product was identified by sequencing as representing a CCK-A receptor fragment. When this PCR product was used to screen the library, ten positive clones were identified in a screening of 4.10(5) plaques, and several of these were sequenced. All had essentially the same sequence contained within 2 of these clones consisted of 427 amino acids and was 92% homologous (87% identity) to the known rat pancreatic CCK-A sequence but only 43% homologous to the gastric CCK-B sequence. The cDNA was subcloned into a pcDNA1 expression vector and transiently expressed in the human embryonic kidney cell line, HK 293. The responses of intracellular Ca2+ in these transfected cells to CCK and gastrin were monitored using video imaging. On the average 40% of the cells responded to CCK-8 by a transient elevation of [Ca2+]i followed by a steady state plateau. CCK was a high and gastrin a low affinity ligand for this signal, corresponding to the actions of these ligands on pepsinogen secretion from chief cells and somatostatin release from D cells. Hence from sequence and second messenger responses, the clone represents the CCK-A receptor presumably responsible for pepsinogen secretion by gastric chief cells and somatostatin release from gastric D cells.

Biophysical and lipofection studies of DOTAP analogs.

In order to investigate the relationship between lipid structure and liposome-mediated gene transfer, we have studied biophysical parameters and transfection properties of monocationic DOTAP analogs, systematically modified in their non-polar hydrocarbon chains. Stability, size and (by means of anisotropy profiles) membrane fluidity of liposomes and lipoplexes were determined, and lipofection efficiency was tested in a luciferase reporter gene assay. DOTAP analogs were used as single components or combined with a helper lipid, either DOPE or cholesterol. Stability of liposomes was a precondition for formation of temporarily stable lipoplexes. Addition of DOPE or cholesterol improved liposome and lipoplex stability. Transfection efficiencies of lipoplexes based on pure DOTAP analogs could be correlated with stability data and membrane fluidity at transfection temperature. Inclusion of DOPE led to rather uniform transfection and anisotropy profiles, corresponding to lipoplex stability. Cholesterol-containing lipoplexes were generally stable, showing high transfection efficiency at low relative fluidity. Our results demonstrate that the efficiency of gene transfer mediated by monocationic lipids is greatly influenced by lipoplex biophysics due to lipid composition. The measurement of fluorescence anisotropy is an appropriate method to characterize membrane fluidity within a defined system of liposomes or lipoplexes and may be helpful to elucidate structure-activity relationships.