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Summary Purpose The nomenclature in clinical nutrition differs locally, among (para)medical disciplines, and both nationally and internationally. The inconsistencies hamper public, professional and scientific discussions. A working group of the German Society of Nutritional Medicine (DGEM) was established to work out definitions for the relevant terms used in nutritional support within Germany. Methods Terms were searched in (inter)national hard print technical literature (medical dictionaries, text books, (inter)national guidelines and online (PubMed, Embase, CINAHL, Google Scholar, general internet). (Inter)nationally agreed definitions published by Clinical Nutrition Societies were preferred to other reports. Results The terms were organised into four categories totaling 53 definitions: 1. Fields and structure: medical nutrition, clinical nutrition, nutrition steering committee, nutritional care, care catering, dietetics (dietary advice), obesity as part of clinical nutrition (obesity team), nutritional support (nutrition support team, malnutrition screening, nutritional support therapy), functional nutrition, nutritional assessment, nutrition therapy plan, nutritional therapy, 2. Nutritional conditions: disease-related malnutrition (starvation induced malnutrition, chronic disease-related malnutrition, acute disease-related malnutrition), cachexia, sarcopenia, specific nutrient deficiencies, refeeding syndrome, 3. Forms of nutrition: diet (regular diet, therapeutic diet, fortified food), artificial nutritional support (oral nutritional supplementation, enteral nutrition, parenteral nutrition) 4. Products: oral nutritional supplements and enteral formulas (whole protein formula, peptide-based formula, free amino acid formula, standard formula), parenteral solutions (total nutrient admixtures, multi-chamber systems, multiple bottle systems). Conclusion A comprehensive list of definitions for terms in nutritional support has been established for the first time and is made available to the international community for further development and discussions.

Summary Background & aims The selection of appropriate outcome variables in clinical nutrition is particularly challenging, since nutrition is an adjunct therapy in most cases. Therefore, its effect may be confounded with the primary therapy, and classic biomedical outcomes may not reflect the effect of the nutritional intervention. This paper scrutinizes different alternatives to the biomedical perspective. Results Five different outcome models are proposed and analyzed for their suitability in clinical nutrition studies: biomedical, patient-centered/-reported, health economic, decision-making, and integration of classical and patient-reported endpoints. Most published studies in the field of clinical nutrition make use of biomedical endpoints, but the growing importance of patient-centered/-reported and health economic outcomes is recognized. We recommend avoiding to focus solely on biomedical endpoints in clinical nutrition studies. The availability and value of a broader set of outcome-models should be acknowledged. Conclusion Patient-centered/-reported, health economic or combined endpoints are particularly useful to assess the effect of nutritional therapies, especially when applied in conjunction with a primary therapy. The proposed outcome models can also contribute to refine clinical nutrition guidelines in assessing the clinical relevance of the study results.

Background: A disturbed epithelial barrier could play a pivotal role in ulcerative colitis (UC). We performed a family-based study analyzing in vivo gastrointestinal permeability in patients with UC, their healthy relatives, spouses, and controls. Methods: In total, 89 patients with UC in remission, 35 first-degree relatives (UC-R), 24 nonrelated spouses (UC-NR), and 99 healthy controls (HC) were studied. Permeability was assessed by a sugar-drink test using sucrose (gastroduodenal permeability), lactulose/mannitol (intestinal permeability), and sucralose (colonic permeability). Data were correlated with clinical characteristics including medical treatment. Results: Increased intestinal permeability was detected significantly more often in UC patients in remission (25/89, 28.1%) compared with HC (6/99, 6.1%; P < 0.001). Similar results were obtained in UC-R (7/35, 20.0%; P = 0.01 compared with HC) regardless of sharing the same household with the patients or not. No difference was found between UC-NR (3/24, 12.5%) and HC. Notably, in UC patients increased intestinal permeability was found in 12/28 patients (42.9%) with pancolitis, 7/30 (23.3%) patients with left-sided colitis, and in 2/19 (10.5%) patients with proctitis (P = 0.04). Gastroduodenal and colonic permeability were similar in all groups. Among patients on azathioprine, increased intestinal permeability was only seen in 1/18 (5.6%) patients. In contrast, in 24/70 (34.3%) patients without azathioprine, an increased intestinal permeability was found (P = 0.005). Conclusions: An increased intestinal but not colonic permeability was found in UC patients in clinical remission that could mark a new risk factor for extensive disease location. Similar findings in healthy relatives but not spouses suggest that this barrier defect is genetically determined. (Inflamm Bowel Dis 2012)

An imbalance of energy intake and energy expenditure leads to obesity. However, little detailed information of energy expenditure and physical activity patterns in obese subjects is available. Therefore, we assessed total energy expenditure (TEE) with its components resting energy expenditure (REE) and activity thermogenesis (AT) and the patterns of physical activity in non-obese and in subjects with different degrees of obesity.TEE and activity pattern were assessed with the SenseWear™ armband in 78 subjects (46 ± 12 years; 28 with normal weight/overweight, 13 each with obesity I° and II°, and 24 with obesity III°). In addition, REE was measured by indirect calorimetry and AT was calculated.Although TEE (and REE) increased with increasing weight category from 2567 (1437) kcal/d in non-obese subjects to 3033 (1931) kcal/d in subjects with obesity III° (p=0.016, p0.001, respectively) body weight adjusted TEE decreased from 33.1 to 22.1 kcal/kg/d (p0.001). This was mainly due to decreased body weight adjusted AT (11.3-5.8 kcal/kg/d, p0.001). AT consisted almost completely of non-exercise AT. In particular, for obese subjects exercise-related AT was negligible.Higher degrees of obesity are associated with decreased body weight adjusted AT. These differences have to be considered for therapeutic strategies.

The Society for Sarcopenia, Cachexia, and Wasting Disease convened an expert panel to develop nutritional recommendations for prevention and management of sarcopenia. Exercise (both resistance and aerobic) in combination with adequate protein and energy intake is the key component of the prevention and management of sarcopenia. Adequate protein supplementation alone only slows loss of muscle mass. Adequate protein intake (leucine-enriched balanced amino acids and possibly creatine) may enhance muscle strength. Low 25(OH) vitamin D levels require vitamin D replacement.

Inflammatory bowel disease (IBD) is frequently associated with malnutrition. Up to 75% of patients with an active phase of IBD suffer from weight loss and hypoalbuminemia. Anaemia and vitamin deficiencies (specifically vitamin D and vitamin B12) as well as trace element deficiencies are also described. Malnutrition with loss of muscle mass and body fat is more frequent in Crohn’s disease than in ulcerative colitis and is usually restricted to the active phase. In quiescent disease malnutrition is uncommon and restricted to patients with short bowel, high output fistulas or a severe stenosis reducing food intake. The aetiology of malnutrition is partly due to anorexia because of food associated symptoms, e.g. pain, and partly due to increased intestinal losses (albumin and blood). An increased energy expenditure in the active phase may only play a smaller role in the development of malnutrition.

Background Cardiopulmonary bypass (CPB) impairs intestinal barrier function and induces systemic inflammation after cardiac surgery. The objective of this study was to evaluate the effect of profound haemodilution (haematocrit 19–21%) during normothermic CPB on gastrointestinal permeability and cytokine release in comparison with a standard haemodilution (haematocrit 24–26%). Methods This was a prospective, controlled, randomized pilot trial of 60 patients without gastrointestinal disease undergoing normothermic CPB (35.5–36°C) for coronary artery bypass graft surgery. Gastrointestinal permeability was measured by the triple-sugar technique (sucrose, lactulose, and mannitol excretion in urine) before and after CPB. Interleukin (IL)-6, IL-10, and tumour necrosis factor alpha (TNFα) were quantified using enzyme-linked immunosorbent assays. Results Data from 59 patients (19–21% haematocrit, n =28; 24–26% haematocrit, n =31) were analysed. Data on gastrointestinal permeability were available for 47 patients (19–21% haematocrit, n =23; 24–26% haematocrit, n =24), blood samples for cytokine analysis from 59 patients. Mannitol excretion was normal before and after surgery without significant differences between the groups (after operation: 5.4% vs 2.9%, P =0.193). Lactulose and sucrose excretion was within a normal range before surgery and increased afterwards without differences between the groups. IL-6, IL-10, and TNFα were elevated after surgery, but there was no difference between the groups [IL-6 ( P =0.78), IL-10 ( P =0.74), and TNFα ( P =0.67)]. Conclusions Profound haemodilution during normothermic CPB brought about significant changes neither in intestinal permeability nor in cytokine release. It may be concluded that a haematocrit of 19–21% during normothermic CPB does not impair intestinal barrier function and cytokine response in patients without gastrointestinal comorbidity.

A modified version of the nutritionDay project was developed for nursing homes (NHs) to increase malnutrition awareness in this area. This report aims to describe the first results from the NH setting.On February 22, 2007, 8 Austrian and 30 German NHs with a total of 79 units and 2137 residents (84+/-9 years of age, 79% female) participated in the NH-adapted pilot test. The NHs participated voluntarily using standardized questionnaires. The actual nutritional intake at lunch time was documented for each resident. Six-month follow-up data were received from 1483 residents (69%).Overall, 9.2% and 16.7% of residents were classified as malnourished subjectively by NH staff and by BMI criteria (20 kg/m(2)), respectively. Independent risk factors for malnutrition included age90 years, immobility, dementia, and dysphagia (all p0.001). In total, 89% of residents ate at least half of the lunch meal, and 46% of residents received eating assistance for an average of 15 min. Six-month mortality was higher in residents with low nutritionDay BMI (20 kg/m(2): 22%, 20-21.9 kg/m(2): 17%) compared to residents with BMIor= 22 kg/m(2) (10%, p0.001). Six-month weight lossor= 6 kg was less common in residents with nutritionDay BMI22 kg/m(2) compared to residents with higher nutritionDay BMI (3.4% vs 12.4%, p0.001).The first nutritionDay in NH provided valuable data on the nutritional status of NH residents and called attention to the remarkable time investment required by NH staff to adequately provide eating assistance to residents. Participation in the nutritionDay project appears to increase malnutrition awareness as reflected in the outcome weight results.

Adipokines are fat-derived hormones and cytokines with immune-modulating and metabolic properties. Most of them are associated with insulin resistance. The aim of the present investigation was to evaluate circulating levels of adipokines and glucose homeostasis in patients with inflammatory bowel disease (IBD) and to evaluate possible associations with the course and characteristics of the disease.Serum leptin, resistin, visfatin, retinol-binding protein-4, adiponectin, glucose, insulin, and inflammatory parameters were analyzed in 93 patients with inactive IBD (49 with Crohn's disease [CD], 44 with ulcerative colitis [UC]), 35 patients with active IBD (18 with CD, 17 with UC), and 37 age- and body mass index-matched healthy controls. Ninety-two patients were followed for 6 mo.Leptin was similar in patients with IBD and controls, whereas resistin and visfatin were increased in patients with active disease but not in those in remission. In active and inactive disease, adiponectin was decreased (P0.001) and retinol-binding protein-4 was increased (P0.001) compared with controls. About 60% of patients with IBD showed increased levels of insulin, whereas serum glucose remained normal, resulting in increased homeostasis model assessment values in most patients. Hyperinsulinemia was associated with the decrease in adiponectin (r = -0.572, P0.001) and proved to be an independent protective factor for 6-mo maintenance of remission (P = 0.016).IBD led to largely similar alterations in circulating adipokines and hyperinsulinemia in patients with CD and those with UC. The unexpected protective effect of hyperinsulinemia on relapse rate denotes the role of the metabolic-inflammatory response as a modulator in IBD.

Summary Background Gastroduodenal and small intestinal permeability are increased in patients with Crohn's disease (CD) and intensive care patients. The relevance of colonic permeability has not yet been adequately investigated. The aim of this study was to investigate the clinical value of sucralose excretion as indicator for colonic permeability in these patient groups. Design After oral administration of four sugars and subsequent analysis of urinary excretion, gastroduodenal and intestinal permeability were calculated from saccharose excretion and lactulose/mannitol (L/M) ratio over 5 h, and sucralose excretion from 5 to 26 h in 100 healthy controls, 29 CD and 35 patients after coronary surgery (CABG). Results In controls, sucralose excretion was highly variable (0·67 ± 0·92%) and not related to small intestinal permeability. In CD and CABG, L/M ratio was increased (0·054 ± 0·060; 0·323 ± 0·253 vs. 0·018 ± 0·001 in controls). Sucralose excretion was increased in 77% of CABG but only in 7% of CD. There was an association between gastroduodenal and intestinal permeability in CD and CABG (r = 0·72, and r = 0·51), but sucralose excretion was not related to either one of these two parameters. Other than a weak association between sucralose and length of stay in intensive care in CABG patients (P = 0·099), sucralose excretion was not related to clinical outcome. Conclusions The proposed cut-off for normal sucralose excretion is 2·11%, but its high variability and lack of association to gastrointestinal permeability or clinical outcome leave it open, if it can provide information beyond established permeability tests.

Summary Background & aims Data regarding the nutritional status, antioxidant compounds and plasma fatty acid (FA) composition in inactive IBD are conflicting. We compared plasma levels of antioxidants and FA of patients with inactive IBD with active IBD and controls. Methods Plasma levels of vitamin C, vitamin E, carotenoids, saturated, monounsaturated and polyunsaturated FA, inflammatory markers and nutritional status were determined after an overnight fast in 132 patients with quiescent IBD (40.6 ± 13.2 years, 87F/45M), 35 patients with active disease (37.9 ± 12.1 years, 25F/10M) and 45 age- and BMI-matched healthy controls (38.1 ± 10.5 years, 39F/6M). Results are expressed as mean ± SD or median [25th percentile;75th percentile]. Results Body mass index (BMI) was normal in inactive (23.9 ± 4.7 kg/m2), active IBD (22.7 ± 4.2 kg/m2) and controls (22.3 ± 1.9 kg/m2). Compared with controls patients with quiescent IBD showed significantly decreased plasma levels of carotenoids (1.85 [1.37;2.56] vs 1.39 [0.88;1.87] μmol/L) and vitamin C (62.3 [48.7;75.0] vs 51.0 [36.4;77.6] μmol/L), increased levels of saturated FA (3879 [3380;4420] vs 3410 [3142;3989] μmol/L) and monounsaturated FA (2578 [2258;3089] vs 2044 [1836;2434] μmol/L) and similar levels of vitamin E and polyunsaturated FA. Results in active disease were similar to inactive disease. Conclusion This study shows that antioxidant status and FA profile in a larger population of IBD patients are disturbed independently from disease activity and despite normal overall nutritional status.

Background and aims A recent study reported that a nonsynonymous SNP rs2241880 (c.898A>G, p.Thr300Ala) within ATG16L1 confers susceptibility to Crohn's disease (CD). We analyzed ATG16L1 c.898A>G in three independent European inflammatory bowel disease (IBD) cohorts from Germany, Hungary and the Netherlands. Methods In total, we included 910 European IBD patients and compared the ATG16L1 c.898A>G genotype frequency with 707 ethnically matched healthy controls. We included patients from 3 populations originating from Germany (CD n =310; ulcerative colitis [UC] n =179), Hungary (CD n =147; UC n =117), and the Netherlands (CD n =157). Subtyping analysis was performed in respect to CARD15 alterations and clinical characteristics. Results We found a highly significant association of c.898A>G to CD. The association was significant ( p =0.0005) for the total CD cohort but also for the individual populations from Germany ( p =0.02) and Netherlands ( p =0.02) whereas in the Hungarian CD patients a clear trend was observed ( p =0.19; OR 1.227, 95% CI 0.910; 1.654). No association was found between c.898A>G and UC. No statistical interactions were observed between ATG16L1 c.898A>G and C ARD15 variants. Furthermore no association to a CD subphenotype was detected. Conclusions We confirm that ATG16L1 variant c898A>G confers a risk variant for CD but is not associated with a distinct CD phenotype.

Objectives We evaluated morphology and function of the gut in patients with chronic heart failure (CHF). Background Intestinal translocation of bacterial endotoxin may contribute to the inflammatory state observed in patients with CHF. The morphology and function of the gut may be abnormal. Methods We studied 22 patients with CHF (age 67 2 years, left ventricular ejection fraction [LVEF] 31 1%, New York Heart Association functional class 2.3 0.1, peak VO2 15.0 1.0 ml/kg/min) and 22 control subjects (62 1 years, LVEF 68 2%, peak VO2 24.7 1.3 ml/kg/min). Bowel wall thickness was assessed by transcutaneous sonography, small intestinal permeability by the lactulose-mannitol test, passive carrier-mediated transport by D-xylose test, large intestinal permeability by sucralose test (5- and 26-h urine collection, high-performance liquid chromatography), and mucosal bacterial biofilm by fluorescence in situ hybridization in biopsies taken during sigmoidoscopy. Results Chronic heart failure patients, compared with control patients, showed increased bowel wall thickness in the terminal ileum (1.48 0.16 mm vs. 1.04 0.08 mm), ascending colon (2.32 0.18 mm vs. 1.31 0.14 mm), transverse colon (2.19 0.20 vs. 1.27 0.08 mm), descending colon (2.59 0.18 mm vs. 1.43 0.13 mm), and sigmoid (2.97 0.27 mm vs. 1.64 0.14 mm) (all p 0.01). Chronic heart failure patients had a 35% increase of small intestinal permeability (lactulose/mannitol ratio: 0.023 0.001 vs. 0.017 0.001, p 0.006), a 210% increase of large intestinal permeability (sucralose excretion: 0.62 0.17% vs. 0.20 0.06%, p 0.03), and a 29% decrease of D-xylose absorption, indicating bowel ischemia (26.7 3.0% vs. 37.4 1.4%, p 0.003). Higher concentrations of adherent bacteria were found within mucus of CHF patients compared with control subjects (p 0.007). Conclusions Chronic heart failure is a multisystem disorder in which intestinal morphology, permeability, and absorption are modified. Increased intestinal permeability and an augmented bacterial biofilm may contribute to the origin of both chronic inflammation and malnutrition. (J Am Coll Cardiol 2007;50:1561‐9) © 2007 by the American College of Cardiology Foundation

Suprasellare Germinome sind seltene Keimzelltumoren, die hauptsachlich bei Kindern und Jugendlichen auftreten und sich typischerweise mit endokrinen Storungen und/oder Kompressionserscheinungen manifestieren. Bei sieben Patienten (sechs mannlich, einer weiblich) wurden die zur Diagnose fuhrenden klinischen und hormonellen Befunde sowie der Langzeitverlauf nach Operation bzw. Radio-/Chemotherapie untersucht. Das mittlere Alter bei Diagnose betrug 19,7 Jahre (Bereich 15–32 Jahre). Als Erstsymptome zeigten sich ein Diabetes insipidus (drei Patienten), ein Libidoverlust (zwei Patienten), eine Pseudopubertas praecox (ein Patient) und ein Wachstumsstopp (ein Patient). Die zur Diagnose fuhrenden Symptome waren hingegen Sehstorungen (funf Patienten), Pseudopubertas tarda (ein Patient) und Hypogonadismus (ein Patient). Alle Patienten erhielten eine transkranielle Bestrahlung mit 40–54 Gy, in einem Fall wurde eine Radiochemotherapie mit Cisplatin, Etoposid und Ifosfamid (PEI) durchgefuhrt. Die Patienten wurden im Mittel uber 14,6 Jahre (7–27 Jahre) nachbeobachtet. Bei zwei Patienten traten Rezidive auf (intrakranial bzw. pulmonal). Nach Therapie bestanden bei allen Patienten ein Panhypopituitarismus und ein Diabetes insipidus. Bei zwei Patienten kam es zur Erblindung, bei zwei weiteren zu einer einseitigen Amaurosis. Bei einem weiteren Patienten traten eine fokale Epilepsie und eine persistierende kognitive Funktionseinschrankung auf. Eine soziale Integration mit Ausubung einer beruflichen Tatigkeit gelang in einem Fall. Im weiteren Verlauf verstarben zwei Patienten an einem Rezidiv bzw. an einer dekompensierten Leberzirrhose bei starker Leberverfettung. Suprasellare Germinome verursachen fruhzeitig endokrine Symptome, jedoch fuhren meist erst die in spateren Tumorstadien entstehenden Sehstorungen zur Diagnosestellung. Auch bei erfolgreicher Therapie ist der Langzeitverlauf durch einen substitutionspflichtigen Panhypopituitarismus, Diabetes insipidus und teilweise durch okulare bzw. zerebrale Defekte gekennzeichnet.

BACKGROUND: A recent study reported that a non-synonymous single nucleotide polymorphism (rs11209026, p.Arg381Gln) located in the IL23R gene is a protective marker for inflammatory bowel disease. AIM: To analyse the frequency of p.Arg381Gln in three independent European inflammatory bowel disease cohorts and to evaluate how this variant influences disease behaviour. METHODS: We assessed a European cohort of 919 inflammatory bowel disease patients and compared the IL23R p.Arg381Gln genotype frequency with 845 healthy controls. Inflammatory bowel disease patients originated from Germany [Crohn's disease (CD): n = 318; ulcerative colitis (UC): n = 178], Hungary (CD: n = 148; UC: n = 118) and the Netherlands (CD: n = 157). Ethnically matched controls were included. We performed subtyping analysis in respect to CARD15 alterations and clinical characteristics. RESULTS: The frequency of the glutamine allele of p.Arg381Gln was significantly lower in inflammatory bowel disease patients compared with controls in a pooled analysis of all three cohorts (P < 0.000001) as well as in the individual cohorts (Germany: P = 0.001, Hungary: P = 0.02 and the Netherlands: P = 0.0002). The p.Arg381Gln genotype distribution was similar between CD and UC. We did not observe either statistical interactions between p.Arg381Gln and CARD15 variants or any significant associations between p.Arg381Gln genotype and subphenotypes. CONCLUSIONS: The p.Arg381Gln IL23R variant confers a protective effect against both CD and UC, but does not determine disease phenotype.

We studied the influence of sequential involvement of the gastrointestinal (GI) tract on the development of multiple organ dysfunction (MOD) after cardiopulmonary bypass (CPB). One hundred and forty-six patients undergoing elective cardiac surgery were included in this prospective observational study. Standardized oral inert-sugar tests (sucrose, lactulose, mannitol, sucralose) were performed before and after CPB in different patients. Enzyme-linked immunosorbent assay of plasma levels of endotoxin core antibodies (EndoCAb) were performed peri-operatively. The functional mucosal surface was calculated from the amount of mannitol absorbed from the GI tract. Lower urine concentrations of absorbed mannitol were observed pre-operatively in patients developing MOD. In binary logistic regression this was an independent parameter. Decreased plasma concentrations of EndoCAb after surgery were seen in every patient, but were more significant in patients developing MOD. A reduced pre-operative functional mucosal surface may predict the early occurrence of MOD after surgery.

Cachexia is a prominent feature in many chronic diseases, but its pathogenesis is still not fully understood. This article reviews recent research into the role of the gut barrier in the pathogenesis of inflammation and cachexia with special emphasis on two potentially catabolic diseases: liver cirrhosis and chronic heart failure.There is increasing evidence that catabolic diseases such as liver cirrhosis and chronic heart failure are associated with increased gut permeability, endotoxemia and enhanced expression of proinflammatory cytokines. In liver cirrhosis normalization of portal hypertension by insertion of a transjugular intrahepatic portosystemic stent shunt obviously causes improvement not only of gut barrier function, but also of nutritional status.Although its pathogenesis is not yet completely understood, proinflammatory cytokines have been implicated in the onset and progression of cachexia. Recent data support the hypothesis that impaired gut barrier function and increased permeability further translocation of endotoxins. Increased endotoxemia might be a potent trigger of systemic inflammatory response which is involved in the pathogenesis of the cachexia syndrome. Thus, it is tempting to speculate that therapeutic strategies for the improvement of gut barrier function will concomitantly improve nutritional status.

Nutritional status frequently deteriorates during chemotherapy in cancer. This is associated with a poor outcome. Since creatine supplementation has shown promising results in various diseases, we investigated the effects of creatine on nutritional status in patients with colorectal cancer undergoing chemotherapy.Thirty patients with colorectal cancer undergoing chemotherapy were randomised to receive either creatine (n=16) or placebo (n=15) for 8 weeks. Body composition was determined with bioelectrical impedance analysis; muscle function by hand grip, hip flexion and knee extension strength and quality of life (QoL) was assessed by the QLQ30 questionnaire.Neither muscle function, body cell mass (BCM) nor QoL improved, but phase angle, a marker of BCM and cell integrity, increased significantly in the intervention patients (5.3+/-0.3 degrees to 5.4+/-0.2 degrees , P=0.030). Evaluating patients with different chemotherapy regimens, however, only intervention patients undergoing less aggressive chemotherapy were shown to benefit, increasing phase angle (5.11+/-0.22 degrees to 5.51+/-0.30 degrees , P=0.043) as well as BCM (27.22+/-2.85 to 29.60+/-3.54kg, P=0.043).Creatine failed to improve muscle mass or function and QoL in colorectal cancer patients but improved bioimpedance parameters that are predictive of poor outcome. Creatine might therefore be useful in patients with milder chemotherapy in order to maintain or increase BCM whereas patients undergoing aggressive chemotherapy however are not likely to benefit.

The ESPEN guidelines on enteral nutrition are the first evidence-based European recommendations for enteral nutrition. They were established by European experts for a variety of disease groups. During guideline development it became evident that terms and definitions in clinical nutrition have been used inconsistently depending on medical disciplines as well as regional and personal preferences. Therefore, to increase explanatory accuracy it was necessary to unify them. In this chapter terms and definitions used throughout all guidelines are explained. Additionally answers to more general questions, which might be important in most indications are dealt with, i.e. use of fibre containing and diabetes formulae.

OBJECTIVES: Genetic variants within DLG5 were recently reported to be associated with inflammatory bowel disease (IBD). The aim of our study was to test for allelic and haplotype associations of six DLG5 variants in 668 IBD patients from two European populations. Furthermore, we evaluated whether DLG5 variants alter gastrointestinal permeability in Crohn's disease (CD). METHODS: Six DLG5 variants (p.R30Q, P.P1371Q, P.G1066G, rs2289308, DLG-e26, p.D1507D) were genotyped in two study populations: (1) German IBD patients (CD n = 250; ulcerative colitis (UC) n = 150) and German healthy controls (n = 422); (2) Hungarian IBD patients (CD n = 144; UC n = 124) and Hungarian healthy controls (n = 205). Subtyping analysis was performed in respect of CARD15 mutations and clinical characteristics. We also tested for differences within DLG5 genotypes in German CD patients with respect to gastroduodenal and intestinal permeability measured by triple-sugar-test. RESULTS: Allele as well as genotype frequencies of DLG5 variants did not differ between IBD patients and controls in either study population. Indeed, the p.R30Q polymorphism was found more frequently in controls than in patients. The distribution of DLG5 genotypes in German and Hungarian CD patients with CARD15 mutations was not different from patients without mutated CARD15. We did also not observe any association between DLG5 variants and clinical parameters. Importantly, DLG5 variants were not associated with gastroduodenal or intestinal permeability. CONCLUSIONS: We could not replicate that DLG5 is a relevant disease susceptibility gene for IBD in German or Hungarian subjects. In addition, we have no evidence that DLG5 variants are involved in altered gastrointestinal permeability in CD.

Normothermic, nonpulsatile cardiopulmonary bypass (CPB) impairs systemic and splanchnic oxygen transport and increases gastrointestinal permeability. It is an important therapeutic goal to avoid splanchnic dysoxia during CPB. Small-dose prostacyclin therapy improves splanchnic oxygen transport and microcirculation in septic patients. In this study, we sought to determine if during cardiac surgery, the prostacyclin analog epoprostenol improves the balance of systemic and splanchnic oxygen transport. Eighteen patients undergoing cardiac valve replacement were randomized to receive either epoprostenol (3 ng x kg(-1) x min(-1)) or placebo during, and for 1 hour after, surgery. Systemic and splanchnic oxygen delivery, consumption, and extraction and arterial, mixed venous, and hepato-venous lactate concentrations were measured before, during, and after CPB. Gastrointestinal permeability was measured 1 day before and 1 day after surgery using the triple sugar permeability test. During CPB, the epoprostenol group had decreased systemic oxygen consumption and splanchnic oxygen extraction (P = 0.024). These effects were not present 1 hour after the end of epoprostenol infusion. The study was not adequately powered to determine whether epoprostenol altered the trend towards increased lactate metabolism and increased postoperative gastrointestinal permeability, nor could we demonstrate any differences between groups in clinically relevant end-points. In conclusion, these findings suggest that during normothermic CPB, small-dose epoprostenol therapy may reduce systemic oxygen consumption and splanchnic oxygen extraction.

Progressive nutritional depletion has been reported during hospital stay. This prospective study compared the proportion of nutritional risk at hospital admission in three European countries and further evaluated nutritional risk at late versus early phase of hospitalization in one hospital.Nutritional risk was determined in Geneva, Switzerland (n = 652), Berlin, Germany (n = 621) and Nice, France (n = 107) at hospital admission, and during hospital stay (0-100 d) in Nice (n = 527) by the Nutritional Risk Index (NRI) = (1.519 x serum albumin, g/l)+41.7 x (present weight/usual weight). NRI score of100: no risk (NR); 97.5-100: mild risk; 83.5-97.5: moderate risk (MR); 83.5: severe risk (SR). Logistic regressions were used to determine the odds ratios (OR) between MR or SR and length of hospital stay (LOS) 16d compared to 1-15 d or nutritional assessment at 16-100 d compared to 1-15 d of hospitalization.Patients, assessed at hospital admission, who were hospitalized16d were more likely (P0.001) to be at MR (OR 2.0, CI 1.4-3.0) or SR (OR 3.3, CI 1.7-6.2) than patients hospitalized 1-15 d. Nice patients assessed at 16-100 d were more likely (P0.001) to be at MR (OR 5.4, CI 2.1-14.3) and SR (OR 14.7, CI 5.4-40.0) than patients assessed at 1-15 d of hospitalization.The risk of MR or SR by NRI was greater in patients assessed during hospitalization than in patients assessed at hospital admission, which suggests that patients evaluated later during hospitalization are at greater risk than patients evaluated in the early phase of hospitalization. Ongoing assessment during hospitalization seems important to identify patients who are at increased risk for complications.

Wir berichten uber den Fall eines 19-jahrigen Patienten, der trotz normaler Testosteronspiegel klinische Zeichen eines Hypogonadismus aufwies. In der weiterfuhrenden Diagnostik zeigte sich das Bild eines Panhypopituitarismus infolge eines β-HCG-produzierenden, intrazerebral metastasierten suprasellaren Germinoms. Aufgrund der paraneoplastischen Produktion von β-HCG bestand trotz gonadotroper Insuffizienz eine ausreichende Stimulation der Leydigschen Zwischenzellen mit normalen Testosteronspiegeln, was zu einer teilweisen Maskierung der gonadotropen Insuffizienz gefuhrt hatte. Der Patient wurde mittels einer kombinierten Radiochemotherapie behandelt und ist seit uber 7 Jahren rezidivfrei.

Summary Background : Reduced lean tissue as well as high fat mass may be independent nutritional risk factors resulting in increased length of hospital stay (LOS). This controlled population study (1707 patients, 1707 volunteers) aimed to evaluate the association between LOS in Geneva and Berlin patients at hospital admission and high fat mass index (FMI, kg/m 2 ) and low fat-free mass index (FFMI, kg/m 2 ), and the respective value of body mass index (BMI) and of FFMI and FMI for nutritional assessment. Methods : Patients (891 men, 816 women) were prospectively recruited at hospital admission and compared to gender-, age- and height-matched healthy volunteers. Fat-free mass and fat mass, determined at admission by 50kHz-bioelectrical impedance analysis, were expressed as indices (FFMI and FMI—kg/m 2 ) to normalize for height. Patients were classified in four groups: normal, low FFMI, high FMI, or low FFMI and high FMI. Logistic regressions were used to determine the association between body composition and LOS. Results : Higher FMI and lower FFMI were found in patients at hospital admission than in sex- and age-matched healthy volunteers. Low FFMI, high FMI, and low FFMI/high FMI combined, adjusted for age, were all significantly associated with longer LOS (high FFMI: 1–5 days OR 2.4, CI 2.0–2.9; 6–10 days OR 2.3, CI 1.8–3.0; ⩾11 days OR 2.8, CI 2.2–3.5); low FMI: 1–5 days OR 1.9, CI 1.6–2.2; 6–10 days OR 2.7, CI 2.0–3.5, ⩾11 days OR 2.1, CI 1.7–2.7; low FFMI/high FMI: 1–5 days OR 7.8, CI 5.3–11.4; 6–10 days OR 13.6, CI 7.8–23.5, ⩾11 days OR 11.8, CI 7.0–19.8). Conclusion : Increased LOS is associated with adiposity (high FMI) and low muscle mass (low FFMI). The current study shows that both depletion of lean tissue and excess of fat mass negatively affect the LOS. Finally, we found that excess fat mass reduces the sensitivity of BMI to detect nutritional depletion.

Ninety-seven percent of neuroendocrine carcinomas are located in the gastrointestinal tract or in the bronchopulmonary tree. Inguinal lymph nodes as the primary tumor site for neuroendocrine carcinoma represent a very unusual location, and have only been described in 2 patient series in the literature. A 64-year-old, previously healthy, Caucasian female presented with a 2-month history of an enlarged inguinal lymph node on the right side. The removed lymph node showed histological and immunohistochemical characteristics of neuroendocrine differentiation (positive for synaptophysin, cytokeratin 20, neuron-specific enolase and chromogranin A). Although extensive investigations including repeated CT and NMR scans, classical endoscopy, wireless capsule endoscopy of the small intestine, octreotide- and MIBG scintigraphy were performed, no other primary tumor was found. Furthermore, there was no evidence of Merkel cell carcinoma on dermatological examinations. A possible explanation for the presence of neuroendocrine carcinomas within the lymph nodes is malignant transformation of preexisting intranodal epithelial nests, which have previously been described in lymph nodes located close to the salivary glands, thyroid gland, breast tissue and pancreas. Since the surgical removal of the affected lymph node, the patient has now been disease-free for 42 months. We therefore consider our case to represent a primary undifferentiated neuroendocrine carcinoma in an inguinal lymph node.

Lamin A and C are components of the nuclear envelope, located at the nucleoplasmatic surface of the inner nuclear membrane within cells. Recently, mutations within LMNA encoding lamin A/C have been associated with various disease entities including cardiomyopathy. We screened heart transplant recipients suffering from dilated cardiomyopathy (DCM) with a positive family history of LMNA mutations. Four index patients and one relative belonging to four unrelated families carrying LMNA mutations were identified. The mutations p.Q355X and p.S22L have not been reported before, whereas p.R190W has already been reported in other studied DCM cohorts. In the patients of the present study, the mean age at manifestation of heart disease was 37.6 years (range 30–45 years), with progression to end-stage heart failure requiring transplantation at a mean age of 45.8 years (range 35–54 years). Three patients presented initially with atrial fibrillation. These data confirm the involvement of LMNA mutations in patients with DCM and extend the mutational spectrum of LMNA. The p.R190W mutation has been reported in different populations and may therefore be useful for analyzing the impact of a specific LMNA mutation on the phenotype of muscle disease.

Background: The effect of non-pulsatile, normothermic cardiopulmonary-bypass (CPB) on the splanchnic blood-flow and oxygen-transport, the hepatic function and the gastrointestinal barrier were observed in a prospective observational study in 31 adults undergoing cardiac valve replacement surgery. Methods: The splanchnic (i.e. hepatic) blood-flow (HBF) was measured by the constant infusion of indocyanine-green (ICG) using a hepatic-venous catheter. Liver function was examined by calculation of lactate uptake, ICG extraction and the monoethylglycinexylidide (MEGX) test. A day before and after surgery the gastrioduodenal and intestinal permeability was measured by determination of sucrose and lactulose/mannitol excretion. Results: Splanchnic blood flow and oxygen delivery did not decrease during and after surgery while splanchnic oxygen consumption (P

Summary Background : Mutations within the NOD2/CARD15 gene have recently been shown to be associated with Crohn's disease. Aims : To investigate the clinical impact of the three common NOD2/CARD15 mutations in patients with Crohn's disease. Methods : We investigated the prevalence of the three common NOD2/CARD15 mutations (Arg702Trp, Gly908Arg, 3020insC) in 180 patients with Crohn's disease, 70 patients with ulcerative colitis and 97 controls. In patients with Crohn's disease, prevalence of NOD2/CARD15 mutations were correlated to clinical and demographical parameters. Results : In Crohn's disease patients, 35.6% carried at least one mutant allele of NOD2/CARD15 mutations compared with 14.3% of patients with ulcerative colitis (P = 0.006) and to 15.5% of controls (P = 0.0001). Genotype phenotype analyses revealed that NOD2/CARD15 mutations determined younger age at disease diagnosis (P = 0.03), ileal disease location (P = 0.01) and ileocecal resections (P = 0.0002). Interestingly, reoperation with resection of the anastomosis was significantly more frequent in patients with NOD2/CARD15 mutations (P = 0.01). Conclusions : Our investigations support the current hypothesis that NOD2/CARD15 mutations are associated with a phenotype of Crohn's disease with younger age at diagnosis, ileal involvement, ileocecal resections and a high risk of postoperative relapse and reoperation. NOD2/CARD15 mutations might therefore be used to identify high risk patients for relapse prevention strategies.

Malnutrition is common at hospital admission and tends to worsen during hospitalization. This controlled population study aimed to determine if serum albumin or moderate and severe nutritional depletion by Nutritional Risk Index (NRI) at hospital admission are associated with increased length of hospital stay (LOS) (and increased hospital cost) in patients admitted to hospitals in 2 European countries.Serum albumin levels and recent weight loss were prospectively determined at hospital admission in Geneva (n = 652) and Berlin (n = 621). Patients were classified as no, mild, moderate or severe risk by NRI. Multiple logistic regressions were used to determine the association between albumin and nutritional risk category and LOS.Patients (24%) were at moderate or severe nutritional risk by NRI. Nutritional risk by NRI, adjusted for age, was associated with LOS of 11 days (moderate: odds ratio [OR] 1.9, 95% confidence interval [CI] 1.4 to 2.7, p.005; severe: OR 2.9, 95% CI 1.6 to 5.3, p.005). Serum albumin was also significantly associated with increased LOS (p.001).The prevalence of nutritional depletion assessed by NRI and albumin was increased with longer LOS. Albumin alone underestimated nutritional risk. Severe nutritional depletion by NRI was significantly associated with LOSor = 11 days in Geneva and Berlin patients. Nutrition screening should take place at hospital admission to determine nutritional risk and risk for longer LOS.

Background/Aims: To search for changes in body composition and energy metabolism associated with the repeatedly observed weight gain of cirrhotic patients after portosystemic shunting. Methods: Twenty-one patients were studied prospectively before and 6 and 12 months after transjugular intrahepatic portosystemic shunt (TIPS) to assess body cell mass by two independent methods (total body potassium counting: body cell mass determined by TBP, BCMTBP, bioelectric impedance analysis: body cell mass determined by BIA, BCMBIA), muscle mass (anthropometry), resting energy expenditure (REECALO) by indirect calorimetry, and nutritional intake by dietary recall analysis. Results: Prior to TIPS patients were hypermetabolic in terms of measured vs. predicted REE (REECALO median 1423 (range 1164– 1838) vs. REEPRED 1279 (1067 –1687) kcal; P< 0.05) and their body cell mass was lower (19.1 (10.9 –33.4) vs. 31.7 (16.8 –47.1) kg; P 5 0.001). After TIPS body cell mass (BCMBIA) increased to 23.5 (12.7 –44.3) ( P< 0.025) and 25.7 (14.2 – 39.7) kg (P 5 0.05) at 6 and 12 months after TIPS and this was confirmed by total potassium counting (BCMTBP before TIPS: 18.8 (10.6 –26.7) vs. 22.4 (12.9 – 28.5) kg at 6 months; P< 0.01). Hypermetabolism persisted throughout the study period. Energy and protein intake increased significantly by 26 and 33%. Conclusions: An increase of prognostically relevant variables body cell and muscle mass contributes to the weight gain after TIPS in malnourished patients with cirrhosis and hypermetabolism. q 2003 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Background/Aim: In recent years, power Doppler sonography has been proposed as a method to assess disease activity in patients with Crohn’s disease. The aim of this prospective study was to evaluate diagnostic criteria for power Doppler sonography by blinded comparison with ileocolonoscopy. Methods: Twenty-two patients with confirmed Crohn’s disease were prospectively investigated with B-mode and power Doppler sonography (HDI 5000, Philips Ultrasound) as well as ileocolonoscopy. Sonography was performed within 3 days before endoscopy. All procedures were performed by experienced examiners who were blinded to the clinical data and other results. Defined ultrasound parameters (bowel wall thickness, vascularization pattern) were used to determine a sonographic score of the activity. The degree of activity was scored from 1 (none) to 4 (high) by both ultrasound and ileocolonoscopy (pattern, extent of typical lesions). For each patient all segments of the colon and the terminal ileum were evaluated by both ultrasound and endoscopy. The weighted ĸ test was used (StatXact software) for statistical analysis. Results: In total, 126 bowel segments were evaluated by both ultrasound and endoscopy. The study showed a high concordance of power Doppler sonography and ileocolonoscopy (weighted ĸ by region: sigmoid colon: 0.81; transverse colon: 0.78; ascending colon: 0.75; cecum: 0.84; terminal ileum: 0.82). Highest concordance was found in the descending colon (weighted ĸ: 0.91; 95% CI: 0.83–0.98). Conclusions: Combination of B-mode and power Doppler sonography has a high accuracy in the determination of disease activity in Crohn’s disease when compared to ileocolonoscopy. The diagnostic criteria established in this study can be useful for the evaluation of inflammatory bowel diseases by ultrasound.

The purpose of this study was to evaluate the patency, functional and haemodynamic results of expanded-polytetrafluoroethylene (ePTFE)-covered transjugular intrahepatic portosystemic shunts in patients with liver cirrhosis.Thirteen patients with an ePTFE-covered transjugular intrahepatic portosystemic shunt stent (TIPSS) were prospectively evaluated at 6 and 12 months and compared with matched controls with mesh-wire uncovered TIPSS.At 6 months, ePTFE-TIPSS showed a significantly lower porto-caval pressure gradient (PCPG) (9 (3-21) mmHg, P = 0.006), a lower rate of dysfunction (8% versus 54%, P = 0.03) and required fewer reinterventions (2 versus 13, P = 0.02); similar results were obtained after 12 months. This resulted in a reduction in the median cost for angiographic surveillance in the covered TIPSS group at 6 and 12 months (36% and 56% compared to the uncovered TIPSS group, P = 0.002), but total procedure-related costs were higher with the ePTFE-TIPSS (6 months: 3730 (3245-6759) versus 1850 (1466-5479) euro/patient; 12 months: 3945 (3460-6759) versus 2295 (1728-5694) euro/patient) due to the higher initial cost of the ePTFE-covered TIPSS.The insertion of ePTFE-covered TIPSS results in better maintenance of lowered portal pressure and fewer reinterventions in patients with liver cirrhosis. There is strong evidence that the use of ePTFE-TIPSS does not require regular surveillance to maintain primary patency, which may then improve cost-effectiveness.

Background & Aims: In nonrandomized trials, photodynamic therapy (PDT) had a promising effect on nonresectable cholangiocarcinoma (NCC). This prospective, open-label, randomized, multicenter study with a group sequential design compared PDT in addition to stenting (group A) with stenting alone (group B) in patients with NCC. Methods: In patients with histologically confirmed cholangiocarcinoma, endoscopic or percutaneous double stenting was performed. Patients fulfilling inclusion criteria were randomized to group A (stenting and subsequent PDT) and group B (stenting alone). For PDT, Photofrin 2 mg/kg body wt was injected intravenously 2 days before intraluminal photoactivation (wavelength, 630 nm; light dose, 180 J/cm 2 ). Further treatments were performed in cases of residual tumor in the bile duct. The primary outcome parameter was survival time. Secondary outcome parameters were cholestasis and quality of life. Results: PDT resulted in prolongation of survival (group A: n=20, median 493 days; group B: n=19, median 98 days; P Conclusions: PDT, given in addition to best supportive care, improves survival in patients with NCC. The study was terminated prematurely because PDT proved to be so superior to simple stenting treatment that further randomization was deemed unethical.

Lactose intolerance with adult-onset is due to the inadequate enzymatic activity of lactasephlorizin hydrolase (LPH). It is frequently seen in patients with Crohn disease, but the mechanism remains to be elucidated. Two DNA genotypes, C/C(-13910) and G/G(-22018), located upstream from the LCT locus, the gene encoding for LPH, were recently identified as representing genetic markers for lactose intolerance. We utilized these two DNA genotypes to study their role in inflammatory bowel disease.We investigated the prevalence of these two DNA variants using specific restriction enzyme digest assays in 166 patients with Crohn disease, in 120 healthy first-degree relatives of Crohn disease patients, in 63 patients with ulcerative colitis and in 187 healthy individuals.The analysis revealed a frequency of 21.4% of the 2 genotypes for adult-type hypolactasia in our studied German cohort of healthy individuals, which is higher than previously reported (15%) based on the hydrogen (H2) breath test. This might indicate a higher sensitivity of genotyping, but it has to be confirmed in larger cohorts. No significant difference was detectable in the frequency of the C/C(-13910) and G/G(-22018) genotypes in patients with Crohn disease (C/C(-13910): 21.7%; G/G(-22018): 22.3%) compared to first-degree relatives (C/C(-13910): 21.7%; G/G(-22018): 20.8%), patients with ulcerative colitis (C/C(-13910): 20.3%; G/G(-22018): 20.3%) and healthy individuals (C/C(-13910): 21.4%; G/G(-22018): 21.4%).The C/C(-13910) and G/G(-22018) genotype of adult-type hypolactasia is not associated with susceptibility to the pathogenesis of Crohn disease and ulcerative colitis.

The development of progressive malnutrition or cachexia is frequent in patients with gastrointestinal cancer - especially in patients with a carcinoma of the pancreas. The cachexia syndrome which is characterised by loss of body weight, negative nitrogen balance and fatigue significantly affects patients' quality of life, morbidity and survival. Because the currently established therapeutical strategies are often disappointing many physicians tended to develop a therapeutical nihilism. Cancer anorexia and cachexia are two distinct syndromes which may have synergistic effects in a patient. This review highlights the growing understanding of the multidimensional pathophysiological background. An algorithm of the current treatment strategies is given. In addition, we discuss new anabolic and anticatabolic agents (e.g. eicosapentanoic acid) and the results from first clinical trials.

It is not yet clear whether intestinal mucosal permeability changes with advancing age in humans. This question is of high importance for drug and nutrition approaches for older adults. Our main objective was to answer the question if small intestinal barrier integrity deteriorates with healthy aging. We conducted a cross‐sectional study including the pooled data of 215 nonsmoking healthy adults (93 female/122 male), 84 of whom were aged between 60 and 82 years. After a 12‐h fast, all participants ingested 10 g of lactulose and 5 g of mannitol. Urine was collected for 5 h afterwards and analyzed for test sugars. The permeability index (PI = lactulose/mannitol) was used to assess small intestinal permeability. Low‐grade inflammation defined by high‐sensitivity C‐reactive protein ≥1 mL/L and kidney function (estimated glomerular filtration rate) were determined in the older age group. The PI was similar in older compared to younger adults (P =0.887). However, the urinary recovery of lactulose and mannitol was lower in the older adults and this change was neither associated with urinary volume nor glomerular filtration rate. The PI was not significantly correlated with low‐grade inflammation or presence of noninsulin‐dependent type 2 diabetes. However, it significantly deteriorated in the copresence of both conditions compared to low‐grade inflammation alone (P =0.043) or type 2 diabetes alone (P =0.015). Small intestinal mucosal barrier does not deteriorate with age per se. But low‐grade inflammation coupled with minor disease challenges, such as type 2 diabetes, can compromise the small intestinal barrier., Until now, it has not been clear if the small intestinal mucosal barrier deteriorates with age per se. We investigated the pooled data of 215 nonsmoking healthy adults, 84 of whom were aged between 60 and 82 years and found similar intestinal permeability results in all age classes. However, in participants with low‐grade inflammation coupled with type 2 diabetes the small intestinal integrity was compromised.

Malnutrition is more common in elderly persons than in younger adults. Ageing itself, however, neither leads to malabsorption nor to malnutrition with the exception of a higher frequency of atrophic gastritis in older persons. Malnutrition in elderly people is therefore a consequence of somatic, psychic or social problems. Typical causes are chewing or swallowing disorders, cardiac insufficiency, depression, social deprivation and loneliness. Undernutrition is associated with a worse prognosis and is an independent risk factor for morbidity and mortality. Awareness of this problem is therefore important. For the evaluation of nutritional status, it must be remembered that most normal values are derived from younger adults and may not necessarily be suitable for elderly persons. Suitable tools for evaluating the nutritional status of elderly persons are e.g. the body mass index, weight loss within the last 6 months, the Mini Nutritional Assessment (MNA) or the Subjective Global Assessment (SGA). An improvement in the nutritional status can be achieved by simple methods such as the preparation of an adequate diet, hand feeding, additional sip feeding or enteral nutrition.

ISIS-2302, an antisense oligonucleotide directed against intercellular adhesion molecule 1, was effective in steroid refractory Crohn's disease in a pilot trial. The aim of this study was to investigate safety and efficacy of ISIS-2302 in chronic active Crohn's disease (CACD).A dose-interval, multicenter, placebo-controlled trial was conducted in 75 patients with steroid-refractory CACD (Crohn's Disease Activity Index [CDAI], 200-400). The primary endpoint was steroid-free remission (CDAI150) at week 14.Only 2 of 60 (3.3%) ISIS-2302-treated and no placebo patients reached the primary endpoint. Steroid-free remission at week 26 (secondary endpoint) was reached in 8 of 60 (13.3%) active treatment and 1 of 15 (6.7%) placebo patients. A greater proportion of ISIS-2302-treated than placebo patients achieved a steroid dose10 mg/day at weeks 14 and 26 (48.3% vs. 33.3% and 55.0% vs. 40.0%, respectively, and a glucocorticoid dose of 0 mg [prednisone equivalent] at week 26 [23.3% vs. 6.7%, respectively]). Treatment with ISIS-2302 was safe. The most common side effects were injection site reactions in the active treatment group (23% in ISIS-2302-treated patients vs. none in placebo patients). No statistically significant differences in the frequency of side effects were detected between dose groups.The trial did not prove clinical efficacy of ISIS-2302 based on the primary endpoint. Positive trends were observed in some of the secondary endpoints.

History and clinical findings A 40-year-old woman complained of weight gain for 10 years. Because of this, she yearly went on a excessive weight reduction diet with weight loss of up to 12 kg. Nevertheless, a total weight gain of 15 kg as well as changing degrees of hypertension, muscular weakness and severe depression were registered during this long period. For 5 years ecchymosis and for 2 years oligomenorrhoea as well as oedema had become evident. Recently large macronodular adrenal glands were found on routine abdominal ultrasound. At the time of clinical investigation early this year she presented with relatively mild Cushing features, such as moon face, central obesity, hirsutism, ecchymosis and hypertension. Investigations Endocrine testing demonstrated suppressed plasma ACTH, low to normal plasma cortisol after overnight fasting and an inverse diurnal rhythm. During 24 hours of fasting plasma cortisol levels and free urinary cortisol excretion were within normal range, but highly elevated under normal food intake. Plasma cortisol levels increased dramatically in response to a lipid-rich meal (5.6-fold), to a protein-rich meal (6.6-fold) and to oral glucose (3.7-fold). Increases in plasma cortisol were closely correlated to increases of gastric inhibitory polypeptide (GIP) concentrations. Subcutaneous injection of octreotide completely inhibited the plasma cortisol and GIP response to oral glucose. Plasma ACTH and cortisol levels did not increase after CRH administration, but fasting plasma cortisol promptly increased after ACTH stimulation. Non-fasting plasma cortisol levels and free urinary cortisol excretion were not suppressed by high doses of dexamethasone. Abdominal computed tomography showed macronodular enlargement of both adrenal glands. Treatment and course The patient underwent bilateral adrenalectomy. Postoperatively, she was treated with replacement doses of hydrocortisone and fludrocortisone. All Cushing features have regressed, a normal menstrual cycle and normal plasma ACTH concentrations have become evident. Conclusion This case report not only presents a very rare cause of Cushing's syndrome--food-dependent or gastric inhibitory peptide (GIP)-dependent hypercortisolism--but it also demonstrates a special course of this disease of relatively long duration. Severe adrenal hyperplasia contrasted with mild clinical symptoms obviously caused by frequent periods of weight reduction diet. Considering this moderate clinical course it might well be that food-dependent hypercortisolism is more frequent than supposed, but not diagnosed owing to relatively mild clinical symptoms.

HISTORY AND CLINICAL FINDINGS A 54-year-old man was admitted to hospital with dyspnoea, giddiness, lack of appetite and burning sensation in the tongue for 3 years. Gastritis was known from his history. Clinical examination showed jaundice, glossitis, systolic murmur and pallhypesthesia of both legs. INVESTIGATIONS Blood and bone marrow investigations revealed pernicious anaemia. At gastroscopy, fundal gastritis was diagnosed and two small polyps of the fundus were removed. Histologically, one of the two polyps turned out to be a gastric carcinoid type 1 (according to [16]). Additional investigations (x-ray, ultrasound of the abdomen, somatostatin-receptor scintigraphy) did not find any metastases. TREATMENT AND COURSE With the diagnosis of a pernicious anaemia the patient was treated with vitamin B12. The original symptoms and the anaemia disappeared. Additional therapy of the gastric carcinoid was not necessary. One year after beginning of the treatment, no signs of the gastric carcinoid were found. CONCLUSION In gastric polyps of patients with pernicious anemia neoplastic transformations will often be found. That is why polypectomy should always be done. The best therapy of the gastric carcinoids type 1, which are the most frequently gastric carcinoids, is endoscopic tumour removal. Surgery is the treatment of choice only for gastric carcinoids type 2 to 4. Concerning quality of life and costs, endoscopic treatment is better for patients with gastric carcinoids type 1 than conventional surgical therapy.

Hintergrund: Zystische Veranderungen von Nebenschilddrusenadenomen treten in 4 bis 5% auf. Diese Tumoren konnen in das Mediastinum verlagert sein. Bisher wurden wenige Fallbeispiele mit anatomisch verlagerten zystischen Nebenschilddrusenadenomen beschrieben. Dabei kam es praoperativ haufig zu Fehldiagnosen, weil die Tumoren anderen Organen zugeordnet wurden. Mogliche Folgen von solchen Fehldiagnosen sind persisiterender Hyperparathyreoidismus und eine hohere chirurgische Komplikationsrate durch eine frustrane Suche des Operateurs nach einem Nebenschilddrusenadenom. Fallbericht: Es wird uber einen 76jahrigen Patienten mit primarem Hyperparathyreoidismus berichtet. Sonographisch wurde der Verdacht auf ein Nebenschilddrusenadenom am linken oberen Schilddrusenpol gestellt. Nebenbefundlich zeigte sich dabei eine zystische Raumforderung im rechten oberen hinteren Mediastinum mit den Verdachtsdiagnosen laterale Halszyste bzw. dysontogenetische Zyste. Die zur Abklarung dieser Raumforderung weiterhin durchgefuhrten Untersuchungen ergaben folgende Differentialdiagnosen: rontgenologisch Struma colli und computertomographisch Osophagusdivertikel, laterale Halszyste sowie bronchogene Zyste. Intraoperativ wurde kein Nebenschilddrusenadenom an der sonographisch verdachtigten Position gefunden. Die Histologie des daraufhin entfernten zystischen Tumors im Mediastinum erbrachte dagegen die Diagnose eines stark aktivierten, zystisch degenerierten Nebenschilddrusenadenoms. Postoperativ normalisierten sich die Serumwerte fur Calcium, Phosphat und Parathormon. Schlussfolgerung: Bei Patienten mit primarem Hyperparathyreoidismus und einer atiologisch unklaren zystischen mediastinalen Raumforderung sollte man unbedingt an das Vorliegen eines anatomisch verlagerten Nebenschilddrusenadenoms denken.

Glucocorticoids are widely used in the treatment of inflammatory bowel disease (IBD). Up- and down-regulated expression of glucocorticoid receptors (GR) has been reported for different chronic inflammatory diseases. The aim of this study was to investigate the expression of GR and their apparent dissociation constant (Kd) in patients with IBD.Thirty-nine patients with IBD (22 with ulcerative colitis, 17 with Crohn's disease) and 35 normal controls were studied. Twenty-five patients did not receive steroids, 14 patients were treated with steroids. Peripheral blood mononuclear cells from patients and controls were isolated using the Ficoll-Hypaque gradient and a whole cell [3H]-dexamethasone binding assay and Scatchard plot analysis were performed to assess GR number and the apparent dissociation constant. Results were expressed as mean +/- standard deviation.Normal controls showed an expression of 3,969 +/- 1,555 GR per cell with an apparent dissociation constant of 6.16 +/- 3.8 nmol/L. IBD patients without steroids had a significant increase both in the expression of GR per cell (6,401 +/- 2,344; p0.0001; Wilcoxon-Mann-Whitney test) and in the apparent dissociation constant (11.02 +/- 7.57 nmol/L; p = 0.006). Expression of GR in IBD patients was suppressed to normal levels under steroid treatment (4,594 +/- 2,237; p = 0.024), but Kd remained elevated (13.56 +/- 9.05 nmol/L). Plasma cortisol levels were not different between IBD patients and the control group.Our data show a systemic increase in GR expression and a decrease in the affinity to the GR in IBD, in contrast to other inflammatory diseases such as rheumatoid arthritis and asthma. These changes point towards a systemic character of IBD, which might be considered in a decision between topical and systemic treatment.

BACKGROUND—Hyperammonaemia is a pathogenetic factor for hepatic encephalopathy that may be augmented after a transjugular intrahepatic portosystemic shunt (TIPS). Experimental data suggest that hyperammonaemia may be caused to a large extent by metabolism of small intestinal enterocytes rather than colonic bacteria. AIMS—To evaluate if ammonia release and glutamine metabolism by small intestinal mucosa contribute to hyperammonaemia in vivo in patients with liver cirrhosis. METHODS—Using TIPS to examine mesenteric venous blood, we measured mesenteric venous-arterial concentration differences in ammonia and glutamine in patients with liver cirrhosis before, during, and after enteral (n=8) or parenteral (n=8) isonitrogenous infusion of a glutamine containing amino acid solution. RESULTS—During enteral nutrient infusion, ammonia release increased rapidly compared with the post-absorptive state (65 (58-73) v 107 (95-119) µmol/l after 15 min; mean (95% confidence interval)) in contrast with parenteral infusion (50 (41-59) v 62 (47-77) µmol/l). This resulted in a higher portal ammonia load (29 (21-36) v 14 (8-21) mmol/l/240 minutes) and a higher degree of systemic hyperammonaemia (14 (11-17) v 9 (6-12) mmol/l/240 minutes) during enteral than parenteral infusion. The mesenteric venous-arterial concentration difference in glutamine changed from net uptake to release at the end of the enteral infusion period (−100 (−58 to −141) v 31 (−47-110) µmol/l) with no change during parenteral nutrition. CONCLUSIONS—These data suggest that small intestinal metabolism contributes to post-feeding hyperammonaemia in patients with cirrhosis. When artificial nutrition is required, parenteral nutrition may be superior to enteral nutrition in patients with portosystemic shunting because of the lower degree of systemic hyperammonaemia. Keywords: hepatic encephalopathy; intestinal metabolism; ammonia; glutamine; enteral nutrition; parenteral nutrition

Objectives Treatment results of advanced hepatocellular carcinoma have remained unsatisfactory; the response rates to intravenous doxorubicin are no better than 20%. Oral tamoxifen has been proposed on the basis of beneficial results in some trials. The aim of this study was to evaluate whether the addition of doxorubicin to oral tamoxifen improves survival compared to oral tamoxifen alone. Methods Thirty-two consecutive patients with a priori defined contra-indications against surgery (transplantation, resection) or chemo-embolization were evaluated to receive chemotherapy. All patients received oral tamoxifen 30 mg bid; 16 also received intravenous doxorubicin 50 mg/m 2 every 4 weeks. The control group consisted of the remaining 16 patients who either were considered unfit for doxorubicin because of a Karnofsky index < 50% (n = 5), cardiac disease (n = 6) or who refused to have cytotoxic drug therapy (n = 5). Results Median survival time was 148 days (95% Cl 89.2-206.8) in the doxorubicin group and 96 days (95% Cl 49.0-143.0) in the control group, and this was not significantly different (P= 0.408), regardless of the presence or absence of cirrhosis. Conclusions In conclusion, the results of our study indicate that combination therapy using doxorubicin and tamoxifen is unlikely to considerably improve survival compared to tamoxifen alone in patients with advanced hepatocellular carcinoma.

To investigate the clinical relevance of interleukin-6 (IL-6) serum levels in patients with Crohn's disease (CD), single point IL-6 measurements in sera from consecutive CD patients and healthy donors (HD), as well as longitudinal measurements during the course of steroid therapy for active CD were performed. Patients with steroid-induced remission were followed until clinical relapse.One hundred thirty-six CD patients without steroid or other immunosuppressive treatment within 2 months and surgical procedures within 3 months before study entry were investigated; 63 patients with active CD were enrolled into the follow-up program. Clinical activity was evaluated by the Crohn's disease activity index (CDAI) and serum IL-6 levels measured by enzyme-linked immunosorbent assay.IL-6 serum levels were significantly elevated in CD patients compared to HD (p0.001). In individual patients serum IL-6 levels correlated with corresponding CDAI scores in a subgroup referred to as primarily inflammatory patients presenting without bowel stenosis, previous intestinal resection, or concomitant inflammatory disorders (r = 0.72, p0.001). Primarily inflammatory patients displayed higher serum IL-6 levels (median: 6.0 pg/ml; range: 1.3-25) than CD patients with bowel stenosis (median: 2.0; range: 1.3-4.9; p0.01) or extensive intestinal resection (median: 1.5; range: 1.3-13.7; p0.001). Longitudinally measured serum IL-6 levels reflected the clinical response during steroid therapy and predicted clinical relapse after steroid-induced remission at week 9 of the treatment protocol.Serum IL-6 is a clinically relevant parameter for CD that correlates with inflammatory activity and implies a prognostic value after steroid-induced remission.

Evaluation of nutritional status is a major problem in patients with liver cirrhosis this is due to water retention and the effect of liver function on protein synthesis. Despite problems evaluating the patient, malnutrition has been found to be a common complication in liver cirrhosis and is associated with poorer outcome. Nutritional restrictions, like protein restriction, are no longer recommended in most patients with liver cirrhosis but are considered harmful. An intake of 1 to 1.5 g/kg protein and 25 to 40 kcal/kg body weight a day is recommended (depending on the situation of the patient). If adequate intake cannot be achieved by oral nutrition, stepwise nutritional support with the introduction of an additional late evening meal, sip feeding or tube feeding is recommended. Parenteral nutrition should be used as a second line treatment for acutely ill patients. Data indicate that improvement of nutritional status prior to liver transplantation might reduce complications.

Abnormalities in lung function are frequent findings in patients with terminal stage chronic liver disease. While spirometric parameters improve early after liver transplantation, a reduction in diffusion capacity has been reported up to 15 months after transplantation. It is unknown to what extent this disturbance in gas exchange occurs among long term survivors after liver transplantation. We assessed lung function in terms of spirometry, and gas exchange as well as pulmonary morphology by high resolution computed tomography (HRCT) in 40 patients 38 months (median, range 20–147 months) after liver transplantation. The prevalence of restrictive or obstructive changes was not different from predicted values. For the whole group of long-term survivors the carbon monoxide transfer coefficient (KCO) was reduced to 71.3 + 12.0 % predicted (P < 0.05). HRCT revealed interstitial changes in only 2/40 (5.0 %), emphysematous bullae in 2/40 (5.0 %) and pleural thickening in 9/40 (22,5 %). Diffusion abnormalities are prevalent in the majority of patients after liver transplantation, whereas spirometric abnormalities are absent also in the long term. The high prevalence of impaired gas exchange and the absence of interstitial lesions imply that changes in pulmonary blood vessels are the most likely cause.

Improvement of health-related quality of life(HRQOL) is a major determinant in decisionmaking forsurgery in patients with Crohn's disease (CD). Thisstudy was designed to investigate the short- andlong-term effect of surgical resection for CD on HRQOL.Sixteen patients were investigated within one weekbefore surgery and 3, 6, and 24 months postoperatively.Besides the Crohn's disease activity index (CDAI), four instruments: the time trade-off technique(TTO), the direct questioning of objectives (DQO), therating form of inflammatory bowel disease patientsconcerns (RFIPC), and the Beck depression inventory-were used for assessment of HRQOL. CDAI decreasedsignificantly after operation and 10 patients remainedin remission for 24 months. Two patients hadpostoperative relapses and went into remission afterprednisolone treatment. Four patients developed chronicactive disease. HRQOL was significantly improved in allpatients three and six months postoperatively. Exceptfor the four patients with chronic active disease, all other patients (N = 12) had alsosignificantly improved HRQOL after 24 months. Inconclusion, surgical resections in CD lead to along-term improvement of HRQOL with the exception ofpatients with chronic active disease. This finding might be taken inconsideration for the indication of surgery inCD.