Search

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.

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.

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 & 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.

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

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.

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.

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.

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 & 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.

Oxidative stress is involved in a number of neurological disorders, including the neurotoxic effects of ethanol. Recent studies have described a neuroprotective potential of alpha-lipoic acid (LC) in several models of neuronal cell death related to oxidative stress. We tested the hypothesis that LC could be effective in preventing ethanol-induced neurotoxicity employing the clonal hippocampa cell line HT22. A 24 h incubation with ethanol 100-600 mM caused a dose-dependent loss of cell viability and a significant increase of the overall intracellular protein oxidation. Coincubation with LC 0.1 mM resulted in a significant decrease of ethanol-related neurotoxicity and a complete prevention of the ethanol-induced intracellular protein oxidation. These results indicate that the radical scavenging properties of LC are effective to ameliorate ethanol-induced neurotoxicity.

Background & Aims: Microorganisms that directly interact with the intestinal mucosa are obscured by fecal flora and poorly characterized. Methods: We investigated the mucosal flora of washed colonoscopic biopsies of 305 patients with bowel inflammation and 40 controls. The microbial cultures were validated by quantitative polymerase chain reaction with subsequent cloning and sequencing, fluorescence in-situ hybridization, and electron microscopy. Results: We found high concentrations of mucosal bacteria in patients with bowel inflammation, but not in controls. The concentrations of mucosal bacteria increased progressively with the severity of disease, both in inflamed and non-inflamed colon. In patients with >10,000 cfu/μL, a thick bacterial band was attached to the intact mucosa without signs of translocation. Patients with inflammatory bowel disease (IBD) and concentrations of mucosal bacteria >50,000 cfu/μL had characteristic inclusions of multiple polymorphic bacteria within solitary enterocytes located next to the lamina propria, without or having no contact with the fecal stream. The identified bacteria were of fecal origin. Conclusions: Our findings suggest that the changes in the mucosal flora in IBD are not secondary to inflammation, but a result of a specific host response. We hypothesize that the healthy mucosa is capable of holding back fecal bacteria and that this function is profoundly disturbed in patients with IBD. GASTROENTEROLOGY 2002;122:44-54

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.

Hereditary amyloidosis is primarily caused by mutations within the transthyretin gene. More than 75 mutations within transthyretin have been reported in causing amyloidosis. The most common mutation is the val30met mutation in the transthyretin protein (TTR-met30) caused by a mononucleic substitution from G to A (GUC to AUC) in the transthyretin gene resulting in the exchange for the amino acids valine to methionine in the corresponding protein sequence. The aim of this work is the development of a specific cleavage of TTR-met30 mRNA in the cell culture system using hammerhead ribozymes. We showed previously that chemically modified nuclease stable Inosine(15.1)-Hammerhead ribozymes are able to target the TTR-met30 mRNA with high specificity on the RNA level (Biochem. Biophys. Res. Commun. 260, 313-317, 1999). Now we present data confirming our observations on the cellular level. We used the wild-type human normal (hn) TTR expressing cell line HepG2 and the stable transfected cell line 293-TTR-met30 for TTR-met30 experiments. We cleaved the TTR-met30 and hnTTR mRNA with specific nuclease stable chemically modified Inosine(15.1)-Hammerhead ribozymes and analyzed the protein after immunoprecipitation and subsequent Western blotting. We were able to downregulate the TTR concentration by 54.5% (100% = 1.5 mg/l TTR) and also specifically to target the TTR-met30 expression in the cell culture system. The therapeutic effect was improved using cationic liposomes resulting in a total downregulation by 92.1 and 62.7% targeting hnTTR mRNA and TTR-met30 mRNA, respectively. The successful employment of Inosine(15.1)-Hammerhead ribozymes in cell culture is therefore a promising tool for the development of a gene therapeutic strategy for hereditary amyloidosis.

Background & Aims: Successful treatment in nonresectable Bismuth type III and IV cholangiocarcinoma is seldom achieved. The aim of this study was to evaluate the effect of photodynamic therapy on cholestasis, quality of life, and survival in these patients. Methods: Nine patients with advanced nonresectable cholangiocarcinomas Bismuth type III and IV, who showed no sufficient drainage (bilirubin decrease Results: After photodynamic therapy, bilirubin serum levels declined from 318 ± 72 to 103 ± 35 μmol/L ( P = 0.0039) with no significant increase during the two monthly follow-ups. Quality of life indices improved dramatically and remained stable (e.g., Karnofsky index from 32.2% ± 8.13% to 68.9% ± 6.1%; P = 0.0078). Thirty-day mortality was 0%, and median survival time was 439 days. Conclusions: This study provides clear evidence that photodynamic therapy is effective in restoring biliary drainage and improving quality of life in patients with nonresectable disseminated cholangiocarcinomas Bismuth type III and IV. Compared with published data, survival time seems to be prolonged. GASTROENTEROLOGY 1998;114:536-542

We studied the use of unconventional therapies of a well-defined population of 105 patients with inflammatory bowel disease (IBD; 72 with Crohn's disease and 33 with ulcerative colitis) who were attending a university out-patient clinic. The following items were used to compare those patients who used unconventional therapies with those who did not. We compared disease-related data, sociodemographic variables, patients' disease-related concerns, and their perceived level of information about IBD. Concerns were measured with the Rating Form of IBD Patient Concerns (RFIPC), inflammatory disease activity was assessed by physicians with the Crohn's disease activity index (CDAI) and the clinical activity index (CAI). Of the 97 (92.4%) patients who answered all questions, 33 (34%) reported using unconventional therapies in addition to conventional therapy. In their level of information about IBD and in their clinical and sociodemographic data, they were not different from the IBD patients who were not using alternative treatments. In their duration of disease, there was a significant difference (p

Introduction. Results from clinical trials often employ the odds ratio or relative risk to compare the proportion of subjects responding to experimental treatment to the proportion responding to control treatment. These measures have the advantage of using a single index to summarize the study results, but neither measure provides information that is intuitively meaningful to clinicians, and both can vary in different ways depending on the response to control treatment. Methods. We calculated the odds ratio and relative risk for responses to control treatment varying from 5% to 75% with a fixed difference of 20% between experimental and control responses. We then compared these values to those for two measures of effect size: number-needed-to-treat (NNT; N Engl J Med 1988; 318:1728-1733) and Probabilistic Index (Statist Med 2006; 25:591-602). Results. The Figure illustrates that with a fixed difference between responses to control and experimental treatment, as the response to control treatment increases, the odds ratio decreases to a plateau and then increases, whereas the relative risk decreases progressively. Since NNT and Probabilistic Index depend only on the difference between response to control and experimental treatment, values for these measures do not change with changing response to control treatment. That is, for a 20% difference between control and experimental responses, the NNT of 5 gives the number of experimental subjects needed to obtain one more success than treating the same number of control subjects. The Probabilistic Index for these same data is 0.6, and gives the probability that a randomly selected experimental subject has an outcome preferable to that from a randomly selected control subject. Conclusion. The NNT and Probabilistic Index depend only on the difference between responses to control and experimental treatment and can help clinicians assess the potential clinical significance of different values of the odds ratio and relative risk.