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Background/Objectives The Refeeding Syndrome (RFS) is a serious complication in patients receiving nutrition support after a period of severe malnutrition. We frequently recognize and diagnose the RFS due to increased awareness. Thus, we observe that many physicians do not know the RFS and that it is rarely diagnosed. The aim of the study was to determine whether physicians in Germany know the RFS. Subjects/Methods A questionnaire with a case vignette about an older person who developed the RFS after initiation of nutritional therapy was submitted to German physicians and fifth year medical students, who were participants of educational lectures. Results Of the 281 participants who answered the respective question, 40 participants (14%) correctly diagnosed the RFS of the case vignette and 21 participants (8%) gave nearly correct answers. Indeed, the majority of the participants did not diagnose the RFS. Conclusions Although the RFS may lead to fatal complications, it is unknown to the majority of the queried physicians. Therefore, there is a call to implement the RFS in respective curricula and increase systematic education on this topic., Author(s): G. Janssen [sup.1], M. Pourhassan [sup.1], R. Lenzen-Großimlinghaus [sup.2], M. Jäger [sup.3], R. Schäfer [sup.4], C. Spamer [sup.5], I. Cuvelier [sup.6], D. Volkert [sup.7], R. Wirth [sup.1], Author Affiliations: [...]

For the diagnosis, prevention and therapy of malnutrition, it is important to estimate the energy and fluid requirements of an individual patient. To our knowledge, it is unknown how accurately medical doctors can estimate the energy and fluid requirements of patients in a clinical routine situation. Hence, we conducted the following survey. A written face-to-face survey about the energy and fluid requirements of and tube feeding and fluid recommendations for a typical patient was performed with 179 medical doctors. An estimation error of >15% was defined as relevant. The results revealed substantial variations in estimating the energy and fluid needs of the patient. A total of 25% of the participants underestimated the energy requirements, and 47% of the participants underestimated the fluid requirements. In addition, 68% of the participants recommended a daily dose of tube feeding that was < 85% of the reference value. A substantial proportion of medical doctors show a lack of knowledge concerning energy and fluid requirements, which demonstrates a need for better medical education with regard to nutrition. European Journal of Clinical Nutrition (2014) 68, 840-843;doi: 10.1038/ejcn.2014.94;published online 21 May 2014, INTRODUCTION Malnutrition is a common comorbidity in clinical medicine. (1) In affluent societies and in times when there is an increasing prevalence of obesity, health-care professionals are often not sensitive [...]

Background: In a preliminary study we showed that antibodies to the endoplasmic reticulum protein calreticulin (CR) occur in primary biliary cirrhosis (PBC) and autoimmune hepatitis type 1 (AIH). Since anti-CR antibodies have also been found in patients with infectious diseases, we investigated their prevalence and immunoglobulin classes in patients with various hepatic and intestinal diseases, hoping to get some information on a possible relationship between an infectious trigger and the induction of a certain class of anti-CR antibodies. Methods: Sera were tested for anti-CR antibodies of the IgA, IgG, and IgM class by Western blotting, using CR isolated from human liver: in autoimmune liver diseases (primary biliary cirrhosis (PBC) (n = 86) and autoimmune hepatitis (AIH) type 1 (n = 57)), alcoholic liver cirrhosis (ALC) (n = 32), viral liver infections (acute hepatitis A (n = 8), acute hepatitis B (n = 20), and chronic hepatitis C (n = 28)), and intestinal diseases (Crohn disease (CD) (n = 30), acute yersiniosis (n = 26)). Sera from 100 healthy individuals served as negative controls. Results: The most prominent finding was the high prevalence of anti-CR antibodies of the IgA class and the similarity in the anti-CR antibody class pattern in PBC (IgA, 62%; IgG, 43%; IgM, 55%) and yersiniosis (IgA, 62%; IgG, 39%; IgM, 42%). Class IgA anti-CR antibodies also occurred frequently in ALC (IgA, 44%; IgG, 41%; IgM, 19%). In contrast, in AIH anti-CR antibodies were predominantly of class IgG (IgA, 28%; IgG, 60%; IgM, 33%). In hepatitis A anti-CR antibodies were absent. In the other diseases they had a low prevalence and were mostly of class IgG (acute hepatitis B: IgA, 0%; IgG, 15%; IgM, 0%; chronic hepatitis C: IgA, 7%; IgG, 21%; IgM, 0%; CD: IgA, 13%; IgG, 20%; IgM, 13%). Of the healthy individuals 7% had anti-CR antibodies exclusively of class IgG. Conclusions: The high prevalence of anti-CR antibodies of class IgA in patients with PBC and yersiniosis as well as in alcoholic liver disease reflects a reactivity of the gut-associated immune system and could imply that a still undefined gut-derived bacterial (?) agent may trigger PBC. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the most severe sequelae of chronic liver disease. The only potentially curative therapeutic options are surgical resection and orthotopic liver transplantation. In most HCC patients, however, at clinical presentation the tumors are unresectable because of multicentricity or poor hepatic functional reserve due to pre-existing cirrhosis or not transplantable because of too advanced tumor stage or severe co-morbidity. In clinical practice, therefore, percutaneous ethanol injection (PEI) and transarterial chemoembolization (TACE) are widely used non-surgical therapeutic strategies. We prospectively analyzed the clinical factors determining the prognosis of 132 inoperable HCC patients and assessed the feasibility, therapeutic efficacy and safety of PEI, TACE and a combination thereof. Mean age of patients was 64 years; 95% of patients had liver cirrhosis and 39% were Okuda stage I, 48% stage II and 13% stage III. Fifteen patients were treated by PEI (group 1), 33 by TACE (group 2), 39 by TACE and PEI (group 3) and 45 received best supportive care (group 4). Survival correlated with the Child-Pugh class of liver cirrhosis and the Okuda stage of HCC. Favorable prognostic parameters were alpha-fetoprotein (AFP) levels <100 ng/ml and absence of portal vein thrombosis. Median survival time was 18 months in group 1 [interquartile range (IQR) 10-19], 8 months in group 2 (IQR 5-15), 25 months in group 3 (IQR 13-36) and 2 months in group 4 (IQR 1-9). Multivariate analysis revealed that patients treated with a combination of TACE and PEI have a significantly better survival than patients receiving either PEI or TACE only (p = 0.001). Patients with inoperable HCCs treated by the combination of TACE and PEI have a clear survival benefit. A favorable outcome can be expected in patients with compensated cirrhosis, a low Okuda stage, a baseline AFP level <100 ng/ml and absence of portal vein thrombosis.

Calreticulin binds Zn2+ with the relatively high affinity/low capacity. To determine the location of the Zn2+ binding site in calreticulin different domains of the protein were expressed in E. coli, using the glutathione S-transferase fusion protein system, and their Zn(2+)-dependent interaction with Zn(2+)-IDA-agarose were determined. Three distinct domains were used in this study: the N + P-domain (the first 290 residues); the N-domain (residues 1-182) and the proline-rich P-domain (residues 180-273). The N + P-domain bound to the Zn(2+)-IDA-agarose and were eluted with an increasing concentration of imidazole. The N-domain also bound 65Zn2+ as measured by the overlay method. The P-domain did not interact with the Zn(2+)-IDA-agarose and it did not bind any detectable amount of Zn2+. Chemical modification of calreticulin with diethyl pyrocarbonate indicated that five out of seven histidines were protected in the presence of Zn2+ but they were modified by diethyl pyrocarbonate in the absence of Zn2+ suggesting that these residues may be involved in Zn2+ binding to calreticulin. We conclude that Zn2+ binding sites in calreticulin are localized to the N-domain of the protein, region that is not involved in Ca2+ binding to calreticulin.

Incubation of a glycoprotein fraction obtained from rat liver plasma membrane which has been previously well characterized using [gamma-32P]ATP results in the phosphorylation of a 230-kDa glycoprotein (pgp230). It is composed of a 120-kDa subunit (pgp120) and a 110-kDa subunit (pgp110) linked by interchain disulfide bonds. Peptide maps of pgp120 and pgp110 suggest extensive similarity in their polypeptide chains. Glycan analysis reveals between four and six hybrid-type oligosaccharide chains for both phosphoproteins. Immunoblotting using monoclonal antibodies and endoglycosidase digestion exclude an identity of pgp120 or pgp110 with the hepatocyte plasma membrane glycoproteins dipeptidylpeptidase IV or the taurocholate transport protein, which co-purify and co-migrate in SDS/PAGE. Protein phosphorylation is Ca(2+)-dependent (K0.5(Ca2+) = 0.35 microM, in the absence of Mg2+). In the presence of Mg2+, the glycoprotein undergoes rapid cycles of phosphorylation and dephosphorylation, resulting in ATPase activity. Analysis of phosphorylated amino acids identifies phosphothreonine as the major one. Photoaffinity labeling with 8-azido-[alpha-32P]ATP demonstrates the presence of one or more ATP binding site(s). Preincubation of pgp230 with various purine or pyrimidine nucleotides (ATP, UTP, TTP, ADP, GDP, AMP, CMP) or known P2-purinoceptor agonists or antagonists (adenosine 5'-[alpha,beta-methylene]triphosphate, 2-methyl-thio-adenosine 5'-triphosphate, suramin) inhibits its phosphorylation by [gamma-32P]ATP. The biological function of pgp230 is unknown at present. Several findings of the present study are compatible with the idea that pgp230 may be involved in a P2-purinoceptor function of the hepatocyte. Following this concept, a mechanism is discussed where a cytosolically exposed high-affinity Ca(2+)-binding site of pgp230 would allow for receptor feedback control, via phosphorylation and dephosphorylation, by sensing changes in cytosolic Ca2+ concentration.

We characterize the specificity of a polyclonal antibody against heat shock protein 60 (hsp60) and present an application for ultrastructural localization studies of this protein. The antibody was obtained from an IgG fraction (AB 121) originally raised against the calcium binding protein calsequestrin by immunoabsorption on isolated rat liver hsp60. As shown by partial N-terminal amino acid sequence analysis of immunoprecipitated proteins AB 121 contained reactivities against hsp60, calsequestrin and the glycoprotein fetuin. In rat heart AB 121 recognized calsequestrin and hsp60. In human and rat liver the only reacting protein was hsp60. In rat erythrocytes the antibody bound to 61 kDa and 58 kDa isoforms of fetuin. According to published data no amino acid sequence homologies nor common motifs are found between calsequestrin, hsp60 and fetuin. As the first application the anti-hsp60 antibody was used for immuno-gold electron microscopical localization of hsp60: in myocardiocytes and hepatocytes of the rat strong labelling was obtained exclusively in mitochondria. No extramitochondrial structures were labelled. The specificity of the antibody and its ability to be visualized by immuno-gold electron microscopy offers the possibility to study the expression of this protein in the liver and in other organs. Possible clinical applications of these studies are discussed, since hsp60 could be a target antigen of autoantibodies in diseases such as autoimmune hepatitis, primary sclerosing cholangitis or primary biliary cirrhosis.

Splenomegaly is a common finding in patients with portal hypertension. In the present study the relation between spleen size and blood flow in the splenic and portal vein was evaluated in 33 patients with alcoholic liver cirrhosis and portal hypertension using pulsed Doppler sonography (Ultramark 9, ATL, Solingen, FRG). There was a significant positive correlation between hilar spleen diameter (HD) and splenic vein diameter (r = .73, p less than .001) as expected as the consequence of portal hypertension. However, a positive correlation between HD and splenic vein flow (SBF) was found (r = .67, p less than .001). Furthermore, there was no negative correlation between HD and flow velocity in the splenic vein (r = .01, n.s.). Portal blood flow (830 +/- 360 ml/min) was fairly constant in spite of considerable variations in SBF (range: 120 to 1200 ml/min). The data of the present study indicate that splenomegaly in patients with liver cirrhosis and portal hypertension is not simply the consequence of portal congestion resulting in decreased SBF. Rather, increased SBF serves to maintain portal blood flow and thereby contributes to portal hypertension. In few patients (15%) SBF increased to more than 11/min may be an important factor for the severity of portal hypertension. Surgical shunt treatment should be adjusted in these patients.

Despite the progress made in recent years, treatment of chronic inflammatory bowel disease remains problematic. The highly individual spontaneous course of such conditions always makes an interdisciplinary management strategy mandatory. In view of the fact that continence-preserving procedures are possible in ulcerative colitis as well as bowel-preserving procedures in Crohn's disease, elective interventions in patients who fail to respond to what is accepted as suitable medication may be considered supplementary to the therapeutic spectrum. A consideration of all the factors involved suggests that too many reservations vis-a-vis surgery are no longer justified.

Each abnormal sonographic finding in the gastrointestinal tract requires further evaluation including other diagnostic means, since differentiation of abdominal diseases is not possible by sonography alone. The pathologic finding of a stomach-cocarde is suspicious for a malignoma. Sonographic control is useful in patients with chronic inflammatory diseases of the intestinal tract, since intestinal as well as extraintestinal complications determining further treatment can be anticipated.