The inverse starving test is not a suitable provocation test for Gilbert's syndrome

<p>Abstract</p> <p>Background</p> <p>Introduction</p> <p>The aim of this study was to evaluate a simple diagnostic test for Gilbert's syndrome (GS), which avoids hospitalization and exposure to toxic test substrates. GS is the most frequent cause of isolated unconjugated hyperbilirubinemia. The nicotinic acid test and the starving test are established approaches to diagnose GS. However, these tests cause considerable side effects or require hospital admission. In single GS patients, we observed rapid serum bilirubin normalization after a standard European lunch (the "inverse starving test").</p> <p>Findings</p> <p>At two consecutive days, 18 profoundly characterized GS patients (7 females, 11 males, median age 34.5 years, range 21–58 years) were investigated with the nicotinic acid test and the inverse starving test. Unconjugated serum bilirubin (UCB) levels were measured before and hourly up to four hours after lunch (median 645 kcal), and after the ingestion of 170 milligrams nicotinic acid, respectively. Patients who consulted their physicians with jaundice were significantly more likely to undergo invasive diagnostic procedures than patients with an incidental finding of elevated UCB, despite UCB levels were indifferent in both groups. Two hours after nicotinic acid ingestion, relative UCB exceeded 1.7 fold the fasting levels (median, range 0.9–2.4 fold, sensitivity 83%). In the inverse starving test, UCB remained almost unchanged three hours after lunch (median 1.0; range: 0.8–1.2 fold). Molecular analysis established the genotype of the TATAA box of the UGT1A1 gene; all patients carried an UGT1A1 promotor polymorphism.</p> <p>Conclusion</p> <p>The inverse starving test is not an appropriate provocation test for patients with suspected GS. The 100% prevalence of the UGT1A1 polymorphism in our cohort underlines that the diagnosis of GS may be substantiated with this simple molecular test in patients with an uncertain diagnosis of GS.</p

Signet-Ring Cell Carcinoma Arising in the Gastric Stump After Duodenopancreatectomy for Ductal Adenocarcinoma of the Pancreas: A Case Report

The development of malignancy in the gastric stump following surgery for peptic ulcer disease is well recognized. There are also few reports on carcinomas occurring after surgery for malignant gastric disease. However, carcinoma of the gastric stump after duodenopancreatectomy is extremely rare. We describe what we believe to be an unusual case of signet-ring cell carcinoma of the gastric stump developing at the anastomotic site 5 years after duodenopancreatectomy for ductal adenocarcinoma of the pancreatic head. We performed remnant gastrectomy and Roux-en-Y gastrojejunostomy as a curative resection. This experience clearly underlies that g astric stump carcinoma (GSC) may mimic metastatic disease recurrence leading to diagnostic confusion after surgery for malignancy. Although an increased risk of gastric stump carcinoma after pancreatoduodenectomy for pancreatic cancer has not been established, the possibility of such a complication should be kept in mind when evaluating patients after gastric resection who present with symptoms of metastatic disease recurrence years after the primary operation. Investigations should be independent of the entity of the primary disease or its localization, since GSC may well be amenable to surgical cure as demonstrated in the presented case. Outpatient follow up results of the last four years indicated no recurrence in this case

Characterisation of a transgenic mouse expressing R122H human cationic trypsinogen

BACKGROUND: The R122H mutation of the cationic trypsinogen was found in patients with hereditary pancreatitis. A transgenic animal carrying this mutation could be useful as a genetic model system of pancreatitis. METHODS: Mice transgenic for the human R122H cationic trypsinogen were generated using the -205 fragment of the rat elastase promoter. The presence of the transgene was assayed in the DNA, in pancreatic mRNA and in zymogen granule lysates. Serum levels of amylase, lipase and cytokines (MCP-1, IL-6) were monitored and the histological appearance of the tissue was investigated. Pancreatitis was induced by 7 hourly injections of 50 μg/kg cerulein. The procedure was repeated twice weekly for 10 consecutive weeks. The animals were sacrificed 24 (n = 8) and 48 hours (n = 8) after the first injection and at the end of the whole treatment (n = 7). RESULTS: The transgene was detected at the genomic level and in pancreatic mRNA. The corresponding protein was found in low amounts in zymogen granule lysates. R122H mice showed elevated pancreatic lipase, but there was no spontaneous development of pancreatitis within 18 months. After induction of pancreatitis, levels of lipase (after 24 hours) and amylase (after 48 hours) were higher in R122H mice compared to controls. Repeated treatment with cerulein resulted in a slightly more severe pancreatitis in R122H animals. Amylase, lipase, and the cytokine levels were similar to controls. CONCLUSION: The R122H transgenic mouse failed to develop a spontaneous pancreatitis but a repeatedly provoked cerulein-induced pancreatitis led to a slightly more severe pancreatitis. The rather small difference in comparison to controls could be due to the low expression of the transgene in the mouse pancreas

Electronic properties of curved few-layers graphene: a geometrical approach

We show the presence of non-relativistic L\'evy-Leblond fermions in flat three- and four-layers graphene with AB stacking, extending the results obtained in [Curvatronics2017] for bilayer graphene. When the layer is curved we obtain a set of equations for Galilean fermions that are a variation of those of L\'evy-Leblond with a well defined combination of pseudospin, and that admit L\'evy-Leblond spinors as solutions in an approriate limit. The local energy of such Galilean fermions is sensitive to the intrinsic curvature of the surface. We discuss the relationship between two-dimensional pseudospin, labelling layer degrees of freedom, and the different energy bands. For L\'evy-Leblond fermions an interpretation is given in terms of massless fermions in an effective 4D spacetime, and in this case the pseudospin is related to four dimensional chirality. A non-zero energy band gap between conduction and valence electronic bands is obtained for surfaces with positive curvature.Comment: 16 pages, 4 figures. Matches the published version. Refined theory that describes the unique combination of isospin states ocurring in curved bilayer graphene sheet

DAOA/G72 predicts the progression of prodromal syndromes to first episode psychosis

The genetic factors determining the progression of prodromal syndromes to first episode schizophrenia have remained enigmatic to date. In a unique prospective multicentre trial, we assessed whether variants at the d-amino acid oxidase activator (DAOA)/G72 locus influence progression to psychosis. Young subjects with a prodromal syndrome were observed prospectively for up to 2 years to assess the incidence of progression to schizophrenia or first episode psychosis. Of the 82 probands with a prodromal syndrome, 21 probands experienced progression to psychosis within the observation period. Assessment of nine common variants in the DAOA/G72 locus yielded two variants with the predictive value for symptom progression: all four probands with the rs1341402 CC genotype developed psychosis compared with 17 out of 78 probands with the TT or CT genotypes (χ2 = 12.348; df = 2; p = 0.002). The relative risk for progression to psychosis was significantly increased in the CC genotype: RR = 4.588 (95% CI = 2.175–4.588). Similarly, for rs778294, 50% of probands with the AA genotype, but only 22% of probands with a GG or GA genotype progressed to psychosis (χ2 = 7.027; df = 2; p = 0.030). Moreover, haplotype analysis revealed a susceptibility haplotype for progression to psychosis. This is one of the first studies to identify a specific genetic factor for the progression of prodromal syndromes to schizophrenia, and further underscores the importance of the DAOA/G72 gene for schizophrenia

The presence of the proteolysis-inducing factor in urine does not predict the malignancy of a pancreatic tumour

BACKGROUND: The proteolysis-inducing factor (PIF) was identified as a tumour product in various gastrointestinal cancers. A previous study in pancreatic cancer patients suggested PIF expression as a tumour marker, which is not related to tumour size. We hypothesized that PIF could be a useful marker to exclude benign pancreatic tumors, as chronic pancreatitis with a pancreatic mass. METHODS: Urine of patients with a pancreatic mass of uncertain malignancy was investigated for PIF expression by Western blot. Sufficient urine protein for analysis was available in 59 patients. The diagnosis was established by histology in 54 patients and by follow up in five patients with chronic pancreatitis. In addition, serum CA19-9 was measured. RESULTS: The sensitivity (specifity) for the detection of a malignant pancreatic tumour was 90% (75%) and 54% (71%) for CA19-9 and PIF, respectively. The sensitivity (specifity) for the distinction of pancreatic cancer from chronic pancreatitis was 89% (80%) and 57% (63%) for CA19-9 and PIF, respectively. CONCLUSION: Evaluation of PIF in urine is of no diagnostic value in patients with a pancreatic mass of unknown malignancy

Open Surgical versus Minimal Invasive Necrosectomy of the Pancreas-A Retrospective Multicenter Analysis of the German Pancreatitis Study Group

Background Necrotising pancreatitis, and particularly infected necrosis, are still associated with high morbidity and mortality. Since 2011, a step-up approach with lower morbidity rates compared to initial open necrosectomy has been established. However, mortality and complication rates of this complex treatment are hardly studied thereafter. Methods The German Pancreatitis Study Group performed a multicenter, retrospective study including 220 patients with necrotising pancreatitis requiring intervention, treated at 10 hospitals in Germany between January 2008 and June 2014. Data were analysed for the primary endpoints "severe complications" and "mortality" as well as secondary endpoints including "length of hospital stay", "follow up", and predisposing or prognostic factors. Results Of all patients 13.6% were treated primarily with surgery and 86.4% underwent a step-up approach. More men (71.8%) required intervention for necrotising pancreatitis. The most frequent etiology was biliary (41.4%) followed by alcohol (29.1%). Compared to open necrosectomy, the step-up approach was associated with a lower number of severe complications (primary composite endpoint including sepsis, persistent multiorgan dysfunction syndrome (MODS) and erosion bleeding: 44.7% vs. 73.3%), lower mortality (10.5% vs. 33.3%) and lower rates of diabetes mellitus type 3c (4.7% vs. 33.3%). Low hematocrit and low blood urea nitrogen at admission as well as a history of acute pancreatitis were prognostic for less complications in necrotising pancreatitis. A combination of drainage with endoscopic necrosectomy resulted in the lowest rate of severe complications. Conclusion A step-up approach starting with minimal invasive drainage techniques and endoscopic necrosectomy results in a significant reduction of morbidity and mortality in necrotising pancreatitis compared to a primarily surgical intervention

Formation of engineering thinking at school during the lesson-game "solar system"

This paper describes the structure, conduct, and the main stages of the interdisciplinary lesson-game. Some data on the principles of educational technology are given. Methodical recommendations for conducting the lesson, as well as examples of didactic tasks are given. The proposed lesson carries the task - to build a model of the solar system. But this is not a simple design and construction but a deep didactic analysis. The results will be the construction of a model of the solar system, as a result of the application of engineering thinking skills in life, as well as the transfer of the project modeling algorithm from theory to practice

Differences in bleeding behavior after endoscopic band ligation: a retrospective analysis

<p>Abstract</p> <p>Background</p> <p>Endoscopic band ligation (EBL) is generally accepted as the treatment of choice for bleeding from esophageal varices. It is also used for secondary prophylaxis of esophageal variceal hemorrhage. However, there is no data or guidelines concerning endoscopic control of ligation ulcers. We conducted a retrospective study of EBL procedures analyzing bleeding complications after EBL.</p> <p>Methods</p> <p>We retrospectively analyzed data from patients who underwent EBL. We analyzed several data points, including indication for the procedure, bleeding events and the time interval between EBL and bleeding.</p> <p>Results</p> <p>255 patients and 387 ligation sessions were included in the analysis. We observed an overall bleeding rate after EBL of 7.8%. Bleeding events after elective treatment (3.9%) were significantly lower than those after treatment for acute variceal hemorrhage (12.1%). The number of bleeding events from ligation ulcers and variceal rebleeding was 14 and 15, respectively. The bleeding rate from the ligation site in the group who underwent emergency ligation was 7.1% and 0.5% in the group who underwent elective ligation. Incidence of variceal rebleeding did not vary significantly. Seventy-five percent of all bleeding episodes after elective treatment occurred within four days after EBL. 20/22 of bleeding events after emergency ligation occured within 11 days after treatment. Elective EBL has a lower risk of bleeding from treatment-induced ulceration than emergency ligation.</p> <p>Conclusions</p> <p>Patients who underwent EBL for treatment of acute variceal bleeding should be kept under medical surveillance for 11 days. After elective EBL, it may be reasonable to restrict the period of surveillance to four days or even perform the procedure in an out-patient setting.</p