Andreas de Weerth

Pancreas and Liver Injury Are Associated in Individuals With Increased Alcohol Consumption

BACKGROUND & AIMS Although chronic pancreatitis and liver cirrhosis are common sequelae of excess alcohol consumption, the 2 conditions are rarely associated. We studied the prevalence of simultaneous liver cirrhosis and chronic pancreatitis in alcoholics. METHODS Postmortem autopsy data from 620 individuals with a history of excess alcohol consumption and 100 nonalcoholics (controls) were analyzed. The individuals were classified into groups based on macroscopic observations of pancreas (no injury, acute pancreatitis, fibrosis, and chronic pancreatitis) and liver (no injury, moderate steatosis, severe steatosis, and cirrhosis). The same classification system was used for histological data, which was used to confirm and correlate macroscopic results. RESULTS Out of the 183 patients with liver cirrhosis, 33 (18%) had chronic pancreatitis and 93 (51%) had pancreatic fibrosis. Out of the 230 patients with severe steatosis, 37 (16%) had chronic pancreatitis and 97 (42%) were found to have a pancreatic fibrosis. Thirty-three (39%) with chronic pancreatitis also showed liver cirrhosis and 37 (44%) showed severe steatosis. Thirty-eight percent of the patients with a pancreatic fibrosis were found also to have liver cirrhosis and in another 40% severe steatosis. Thirty-five patients showed neither hepatic or pancreatic injury. We found no chronic pancreatitis or liver cirrhosis in the control group (n = 100). CONCLUSIONS Contrary to common belief there is a close association between pancreatic and hepatic injury in patients with increased alcohol consumption, and the degree of organ damage between the 2 organs correlate.

Saccharomyces boulardii to Prevent Antibiotic-Associated Diarrhea: A Randomized, Double-Masked, Placebo-Controlled Trial

Antibiotic-associated diarrhea is an important clinical problem, associated with morbidity, mortality and healthcare costs. Our randomized, placebo controlled multicenter trial do not support the efficacy of Saccharomyces boulardii in the prevention of antibiotic-associated diarrhea.

Clinical features of critically ill patients with Shiga toxin-induced hemolytic uremic syndrome.

Objective:In Spring 2011, an unprecedented outbreak of Shiga toxin–producing Escherichia coli serotype O104:H4–associated hemolytic uremic syndrome occurred in Northern Germany. The aim of this study was to describe the clinical characteristics, treatments, and outcomes of critically ill patients with Shiga toxin–producing E. coli–associated hemolytic uremic syndrome during this outbreak. Design, Setting, and Patients:Multicenter, retrospective, observational study of critically ill adult patients with Shiga toxin–producing E. coli–associated hemolytic uremic syndrome in six hospitals in Hamburg, Germany, between May 2011 and August 2011. Measurements and Main Results:During the study period, 106 patients with Shiga toxin–producing E. coli–associated hemolytic uremic syndrome were admitted to eight ICUs. The median age was 40 years (range, 18–83) with a female:male ratio of 3:1. The median time from onset of clinical symptoms to hospital admission was 3 days and from hospital to ICU admission an additional 3 days. A total of 101 patients (95.3%) had acute renal failure and 78 (73.6%) required renal replacement therapy. Intubation and mechanical ventilation were required in 38 patients (35.8%) and noninvasive ventilation was required in 17 patients (16.0%). The median duration of invasive ventilation was 7 days (range, 1–32 days) and the median ICU stay was 10 days (range, 1–45 days). Fifty-one patients (48.1%) developed sepsis; of these 51 patients, 27 (25.4%) developed septic shock. Seventy patients (66.0%) developed severe neurological symptoms. Ninety-seven patients (91.5%) were treated with plasma exchange and 50 patients (47.2%) received eculizumab (monoclonal anti-C5 antibody). The mortality rate was 4.7%. Mild residual neurological symptoms were present in 21.7% of patients at ICU discharge, and no patient required renal replacement therapy 6 months after ICU admission. Conclusions:During the 2011 Shiga toxin–producing E. coli–associated hemolytic uremic syndrome outbreak in Germany, critical illness developed rapidly after hospital admission, often in young women. The infection was associated with severe neurological and renal symptoms, requiring mechanical ventilation and renal replacement therapy in a substantial proportion of patients. Overall, recovery was much better than expected.

The cholecystokinin2-receptor mediates calcitonin secretion, gene expression, and proliferation in the human medullary thyroid carcinoma cell line, TT.

Gastrin-induced release of calcitonin from medullary thyroid carcinomas (MTC) is based on the expression of the cholecystokinin(2)-receptor (CCK(2)R) in these tumors. Recently, we have shown that the CCK(2)R is expressed not only in MTC but also in C-cells within the normal thyroid gland. The functions of the CCK(2)R in MTC and C-cells are largely unknown. We therefore explored the effects of gastrin-induced CCK(2)R stimulation in the highly differentiated MTC cell line, TT. CCK(2)R expression in TT-cells is detectable by RT-PCR as well as immunocytochemistry. Stimulation of the CCK(2)R by gastrin induces immediate release of calcitonin from TT-cells. Moreover, quantitative (LightCycler) RT-PCR demonstrates that gastrin stimulates transcription of the calcitonin and chromogranin A genes in TT-cells. TT-cell proliferation, assessed by counting of viable cells and (3)H-thymidine uptake, is markedly increased by gastrin. This effect is inhibited by the CCK(2)R-specific antagonist L-365,260. Our findings suggest physiological functions for the CCK(2)R in calcitonin-secretion and gene expression as well as a pathophysiological role in MTC proliferation. CCK(2)R antagonists might have therapeutic potential in these tumors.

Risk Factors for Development of Hemolytic Uremic Syndrome in a Cohort of Adult Patients with STEC 0104:H4 Infection

The outbreak of Shiga toxin producing E.coli O104:H4 in northern Germany in 2011 was one of the largest worldwide and involved mainly adults. Post-diarrheal hemolytic uremic syndrome (HUS) occurred in 22% of STEC positive patients. This study’s aim was to assess risk factors for HUS in STEC-infected patients and to develop a score from routine hospital parameters to estimate patient risks for developing HUS. In a cohort analysis, adult patients with STEC infection were included in five participating hospitals in northern Germany between May and July 2011. Clinical data were obtained from questionnaires and medical records, laboratory data were extracted from hospitals’ electronic data systems. HUS was defined as thrombocytopenia, hemolytic anemia and acute renal dysfunction. Random forests and multivariate logistic regression were used to identify risk factors for HUS and develop a score using the estimated coefficients as weights. Among 259 adults with STEC infection, vomiting (OR 3.48,95%CI 1.88–6.53), visible blood in stools (OR 3.91,95%CI1.20–16.01), age above 75 years (OR 3.27, 95%CI 1.12–9.70) and elevated leukocyte counts (OR 1.20, 95%CI 1.10–1.31, per 1000 cells/mm3) were identified as independent risk factors for HUS. A score using these variables has an area under the ROC curve of 0.74 (95%CI 0.68–0.80). Vomiting, visible blood in stools, higher leukocyte counts, and higher age indicate increased risk for developing HUS. A score using these variables might help to identify high risk patients who potentially benefit from aggressive pre-emptive treatment to prevent or mitigate the devastating consequences of HUS.

Evidence for CCKB receptors in the guinea-pig kidney: localization and characterization by [125I]gastrin binding studies and by RT-PCR

Two types of receptors for gastrin and cholecystokinin (CCK) have been identified in the gastrointestinal tract and in the central nervous system: CCKA and CCKB receptors. Here we report evidence for the expression of CCKB receptors in the guinea-pig kidney. Specific binding sites for [125I]gastrin were detected in sections of the guinea-pig kidney: Binding was saturable, pH-, temperature- and time-dependent, and specific for gastrin-related peptides. The potencies for inhibition of binding of [125I]gastrin were CCK-8 > gastrin 17-I > CCKB receptor antagonist L-365,260 > des(SO3)CCK-8 > CCKA receptor antagonist L-364,718. Autoradiography demonstrated specific [125I]gastrin binding to medullary collecting ducts and to a much lesser extent to glomeruli, but not over other structures. CCKB receptor cDNA fragments were amplified by RT-PCR from total kidney, isolated tubuli and from tissues known to express CCKB receptors such as stomach and brain. The kidney might therefore be a previously unidentified site of action for gastrin and cholecystokinin-related peptides.