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Background: Inflammatory bowel disease (IBD) results from an aberrant immune response to the indigenous intestinal flora in genetically susceptible hosts. Therefore, the study of candidate genes involved in host pathogen interactions is of key interest., Methods: In this two-center, retrospective German and Hungarian cohort study, patients with Crohn's disease (CD) (n = 379; German n = 235, Hungarian n = 144) and ulcerative colitis (UC) (n = 263; German n = 145, Hungarian n = 118) and healthy controls (n = 605; German n = 403, Hungarian n = 202) were genotyped for the presence of the CD14 c.1-260C>T promoter variant and the TLR4 c.896A>G (p.D299G) variant by melting curve analysis using fluorescence resonance energy transfer probes. Data were stratified according to the presence of NOD2 (CARD15) mutations and a detailed genotype-phenotype analysis was performed., Results: In the German cohort the CD14 single-nucleotide polymorphism was associated with UC, but not CD (UC p = 0.016 vs. CD p = 0.190), while the opposite was found in the Hungarian cohort (UC p = 0.083 vs. CD p = 0.019). No association of IBD with the TLR4 single-nucleotide polymorphism was found in either cohort (UC p = 0.430, CD p = 0.783 vs. UC p = 0.745, CD p = 0.383)., Conclusion: IBD appears to be associated with the CD14 c.1-260C>T promoter variant in Germans and Hungarians, but not with the TLR4 c.896A>G (p.D299G) variant.

Background and Aims: To evaluate genotyping for two DNA variants (c.1993+327C>T and c.1438+117G>A), recently found to be associated with adult-type hypolactasia, in the diagnosis of lactose intolerance., Methods: In total, 166 consecutive patients with gastrointestinal symptoms mimicking hypolactasia admitted to the clinic between March 2002 and December 2002 were included. Genotyping for the two DNA variants (c.1993+327C>T and c.1438+117G>A) and standard H2 breath test was performed., Results: Among 116 patients with positive H2 breath test, the c.1993+327C variant was detectable in 106 (91.4%) patients. Among 50 patients with negative H2 breath test, the c.1993+327C variant was seen in 2 patients. Sensitivity, specificity, positive and negative predictive values for the c.1993+327C variant were 91.4, 96.0, 98.1 and 82.8%, respectively. Genotyping for the c.1438+117G variant did not bring any additional information. Among 4 of the 10 patients with positive H2 breath test but negative for the c.1993+327C and the c.1438+117G variant,further evaluation revealed other diseases known to cause secondary hypolactasia such as celiac disease and short bowel syndrome., Conclusion: In symptomatic patients, genotyping for the DNA variant c.1993+327C is a reliable test for adult-type hypolactasia with high sensitivity and specificity and thus provides a new tool in the diagnostic workup of hypolactasia., (Copyright (c) 2005 S. Karger AG, Basel.)

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., (Copyright 2005 S. Karger AG, Basel.)

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.

Hypokalaemic periodic paralysis is a fairly common complication of hyperthyroidism in Asian populations, but a rare event in Caucasians. In the present work we describe 2 male Caucasian patients with thyrotoxic periodic paralysis (TPP) as initial clinical manifestation of Graves' disease. Further diagnostic procedures demonstrated unilateral adrenal adenoma and hyperandrogenaemia in both patients. To date, only few data are available concerning the hormonal status of Caucasian patients with TPP. The constellation of TPP and adrenal adenomas with increased levels of androgens has not been described previously. Since androgens are capable of inducing sodium-potassium ATPase, which is thought to be centrally involved in the pathogenesis of TPP, hyperandrogenaemia may have triggered the manifestation of paralytic attacks in our patients. It may be of interest to focus not only on thyroid dysbalances in patients with TTP but also to investigate other hormonal disturbances., (Copyright 2003 S. Karger AG, Basel)

Trimetrexate (TMTX) is a new antifolate which avoids competition for cellular uptake with folinic acid (FA). A regimen of sequential TMTX, FA and 5-fluorouracil (5-FU) has shown efficacy in patients with colorectal cancer. Therefore, we treated 34 previously untreated patients with metastatic colorectal cancer with a weekly chemotherapy regimen consisting of 110 mg/m(2) of TMTX intravenously, then 24 h later 200 mg/m(2) of FA (i.v.) and 500 mg/m(2) of 5-FU (i. v.). Thereafter, 7 doses of oral FA (15 mg) were given at 6-hourly intervals. A treatment cycle consisted of 6 weeks of treatment, then 2 weeks of rest. All patients were treated as outpatients unless complications arose. Thirty-three patients were assessable for tumor response, and all 34 patients were assessable for toxicity. Twelve patients (36%; 95% confidence interval: 25-49%) achieved a partial response. The median duration of response was 8.5 months, and median survival was 14 months. The most common toxicity was diarrhea of grade 3/4, observed in 22% of treatment cycles; this decreased to 8% with early loperamide treatment. Hematologic toxicity was mild. The sequential administration of TMTX, FA and 5-FU is an active regimen in the first-line treatment of metastatic colorectal cancer and warrants further studies., (Copyright 2000 S. Karger AG, Basel)

Background: Intravenous iron and erythropoietin have been shown to be effective in Crohn's disease-associated anemia. The aim of this study was to test the sequential treatment of anemia in ulcerative colitis with intravenous iron in the first phase and erythropoietin in the second., Patients and Methods: Twenty patients with ulcerative colitis-associated anemia (hemoglobin < or = 10.5 g/dl) entered this open-label trial. In the first phase all patients received intravenous iron saccharate for 8 weeks. A response was defined as an increase in hemoglobin > or = 2.0 g/dl; a final hemoglobin >10.5 g/dl was regarded as full response, < or = 10.5 g/dl as partial response. A hemoglobin increase < 2.0 g/dl was regarded as nonresponse. In the second phase (n = 4) erythropoietin was initiated in patients without response. Patients with partial response were continued on iron saccharate for another 8 weeks., Results: During the first phase the hemoglobin increased from 8.3 to 11.9 g/dl (mean hemoglobin difference 3.6+/-2.3 g/dl, p < 0.001). Fifteen patients (75%) showed a full response (mean hemoglobin difference 4.5+/-1.5 g/dl), 1 (5%) a partial response (hemoglobin difference 2.1 g/dl) and 4 no response (mean hemoglobin difference 0.4+/-1.8 g/dl) with a need for blood transfusions in a single patient. In the second study phase erythropoietin was highly effective in previous nonresponders (mean hemoglobin difference 3.3+/-1.9 g/dl). The single patient with partial response had a minor hemoglobin increase (hemoglobin difference 1.0 g/dl)., Conclusion: Most patients with ulcerative colitis-associated anemia improve on intravenous iron alone. Erythropoietin is effective in those who do not respond.

An oral folate absorption test was performed in 100 consecutive patients with Crohn's disease (CD) and 20 healthy individuals to investigate the frequency of abnormal folate absorption in regard to the site of the disease and to investigate the possibility of defining a subgroup of patients requiring parenteral folate supplementation. The described oral folate absorption test can be performed quickly on an outpatient basis and is capable of distinguishing patients with altered folate absorption from those with normal folate absorption. In 25 patients, abnormal folate absorption was detected. 16 patients showed impaired folate absorption as indicated by a marked but insufficient increase in serum folate levels after oral folate intake, whereas no increase of the serum folate levels was detected in the remaining 9 patients. Abnormal folate absorption was not correlated with disease extent or activity. In patients with only impaired folate absorption, it might be sufficient to increase dietary intake of folates. In the remaining patients with no measurable increase of serum folate levels after oral folate intake, i.e. about 10% of all patients with CD, parenteral folate supplementation could be considered.

Previous studies have shown that pseudocholinesterase (PCHE) is low in patients with Crohn's disease (CD). This finding, however, failed to be of clinical relevance due to the wide normal range. PCHE consists of four main molecular forms designated as C1, C2, C3 and C4 according to their electrophoretic mobility. The question of the present study was to assess the influence of CD on the distribution and pattern of the PCHE isozymes. We therefore investigated the electrophoretic separation of PCHE in 16 healthy volunteers (HV), in 15 patients with quiescent CD (QCD; CD activity index: median = 71, interquartile range = 44-122) and in 10 patients with active CD (ACD; CD activity index: 229, 173-304). In most of the cases total serum PCHE activity was within the normal range even in patients with active CD. No changes of the isozyme pattern were found but the percentage distribution was significantly influenced by the inflammatory activity in patients with active CD:C1 (HV: 14.7%, 13.7-18.1%; QCD: 16.0%, 9.8-19.9%; ACD: 8.5%, 2.9-12.5%, p < 0.01) and C2 (HV: 8.0%, 6.7-10.5%; QCD: 9.0%, 7.9-9.7%; ACD: 6.7%, 3.2-8.6%, p < 0.05) were decreased in active CD while the C4 component (HV: 66.8%, 62.5-69.9%; QCD: 63.1%, 54.9-73.8%; ACD: 77.3%, 70.7-90.1%, p < 0.01) was increased. The percentage of the C3 band (HV: 5.7%, 4.6-6.9%; QCD: 6.8%, 4.6-8.4%; ACD: 5.3%, 2.8-6.8%, NS) was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Glucose intolerance is well known in acute pancreatitis. The question of this study was to clarify, if fat used partly instead of glucose in the parenteral nutrition of these patients allows to reduce the insulin necessary to control the blood glucose. A second question was if hypertriglyceridemia is caused by long term infusion of fat in such patients. 10 patients with acute necrotising pancreatitis were divided in two groups: group I (5 patients) were infused with a parenteral nutrition with fat, group II (5 patients) with a parenteral nutrition without fat. As parameters the amount of insulin needed to maintain the blood glucose at levels less than 200 mg% and the serum triglycerides were used. The blood glucose was controlled three times a day. For statistical evaluation the Student-t-test was used. The patients in group I (parenteral nutrition with fat) were infused 44 days and received insulin on 40 days. 69 units insulin/day were needed with a glucose dose of 243 g/day. The insulin dose per 100 g glucose was 29.9 U. The fat dose was 74 g/day. Group II (parenteral nutrition without fat) was infused 45 days and received insulin on 38 days. 103 units insulin/day were needed metabolized 295 g of glucose. The insulin per 100 g glucose was 28.7 units. The dose of insulin per 100 g glucose was not different between the two groups. In 1 patient a hypertriglyceridemia occurred after infusion of fat and disappeared immediately after withdrawal of the fat infusion. In the other patients no hypertriglyceridemia occurred during fat infusion. The parenteral infusion of fat has no influence on the glucose intolerance of patients with acute necrotising pancreatitis.

Polypoid lesions of the colon are commonly accepted risk factors for the development of carcinomas of the colon. Fifty-two of 266 patients with one or more polypoid lesions of the colon showed a carcinoma in one of the polyps, 6 patients had a second carcinoma. Our study demonstrates the importance of preoperative investigation of the total colon in patients with carcinoma of the colon. Furthermore, the necessity of total exstirpation of each polypoid lesion is discussed.

Tube feeding with elemental and peptide diets is used as therapy for the acute phase of Crohn's disease. It should improve the nutritional status of the patients and reduce bacterial counts in the intestine. In this study we investigated the frequency of bacterial contamination of solutions of chemically defined diets and the clinical effects of the application of contaminated diets (stool frequency, body temperature, leucocyte counts). 15 patients with acute phase of Crohn's disease were treated with chemically defined diets over a total period of 323 days via a nasoduodenal tube. 7 patients received BSD, 8 patients Peptisorb. In all 36 BSD solutions examined in concentration procedures we found microbes, most frequently Streptococcus and Bacillus spp. Without concentration procedures it was possible to cultivate bacteria in 12% out of BSD solutions and in 81% out of Peptisorb solutions; in BSD mostly Streptococcus and in Peptisorb solution E. coli, Bacillus spp. and aerobic spore forming bacilli. Stool frequency, body temperature and leucocyte counts did not show significant differences after application of contaminated solutions in comparison to the others. Deterioration of the disease has not been observed in any case.

The role of liver, muscle, kidney and gut in the assimilation of intravenously administered glycylleucine was investigated in 8 mongrel dogs. The rates of disappearance of glycylleucine during its passage across liver, muscle, kidney and gut were 1487 +/- 80, 740 +/- 216, 1436 +/- 115, and 602 +/- 103 mumol/(min x kg B.W.), respectively. The infusion of glycylleucine greatly altered the fluxes of glycine and leucine across these organs. The major alterations included increases in the uptake of glycine by the liver and that of leucine by the muscle, and increases in release of leucine by liver and kidney. We conclude that all organs are involved in the assimilation of intravenously administered glycylleucine, but with varying importance. Although liver and kidney appear to be the dominant organs for the assimilation of glycylleucine, the metabolism of glycine is chiefly accomplished in the liver, and that of leucine is chiefly accomplished in the muscle.

The concentration of 19 serum proteins was determined by radial immunodiffusion in 23 patients with Crohn's disease before and after treatment with parenteral nutrition. The results were related to body weight and Crohn's Disease Activity Index. An increased serum concentration of retinol-binding protein, prealbumin, and transferrin paralleled an increase of body weight. Alpha-1-glycoprotein, alpha-2-chymotrypsin, alpha-1-antitrypsin, C-reactive protein, and haptoglobin decreased during parenteral nutrition and showed a positive correlation to the Crohn's Disease Activity Index. The determination of certain proteins is clinically useful, since their serum concentration reflects the influence of parenteral nutrition on nutritional status and disease activity. Measurement of these proteins provides a useful guide to the management of patients with Crohn's disease treated with parenteral nutrition.

Using a subhuman primate (baboon) we have investigated the utility of a 20% mixture of amino acids and dipeptides as the nitrogen source for total parental nutrition. The mixture, besides containing all 8 essential amino acids and a number of non-essential amino acids (glutamate, aspartate, arginine, histidine, serine, ornithine and alanine), contained 6 dipeptides (Gly-Ile, Gly-Leu, Gly-Val, Gly-Tyr, Gly-Gln, and Ala-Gln) and acetyl-cysteine. A week of total parenteral nutrition was preceded by one week of oral feeding. The caloric intake and composition during the two periods was identical except for the nitrogen source, which was intact protein during the oral period, and the mixture of amino acids and dipeptides during the parenteral period. There was no significant difference between gain in body weight or nitrogen balance during the two periods. There were selective increases in plasma and muscle concentrations of amino acids during the parenteral period, which appeared to reflect the amino acid enrichment of the nitrogen source. The efficient utilization of dipeptides was evidenced by their small concentrations in plasma and urine. The urinary excretion of dipeptides was about 1% of the amount infused. This efficiency of dipeptide utilization persisted even when the infusion rate of the amino acid and dipeptide mixture was increased by 7-fold. There was no alteration in liver, kidney, and immune function during the parenteral period. The data indicate the efficacy and safety of the mixture of amino acids and dipeptides as the nitrogen source for parenteral nutrition.

In 10 patients with acute pancreatitis the lipid- and lipoprotein-metabolism was studied. In all patients blood samples were drawn for estimation of the fasting concentration of the lipoproteins. In 7 patients the postheparinlipasesystem was testet by an intravenous heparintest. Afterwards, 0.2 g fat/kg bodyweight were injected intravenously in 2 min. Before, 5, 10, 30 and 40 min after injection blood was drawn. Lipids were estimated by means of full encymatic methods, lipoproteins were determined according to the lipid research clinics method, NIH, using a combination of ultracentrifuge and polyanion precipitation. In comparison with healthy people the cholesterol, specially the LDL fraction was low. Additionally the triglycerides were elevated in 3 patients, caused by elevation of the VLDL fraction. After injection of heparin in all patients the triglyceride concentrations fell. That shows a functionating lipoprotein lipase system. Intravenously injected fat was eliminated in all patients with an elimination rate between 1 and 2 %/min. From these results it is concluded that exogenous fat is eliminated sufficiently from serum in acute pancreatitis. There is no sign for disturbed fat metabolism in these patients. Therefore the contraindication for fat emulsions in acute pancreatitis does not seem to be justified. Due to the fact of glucose intolerance in these patients fat emulsions could be used for an adequate supply of energy. Patients with a hyperlipoproteinemia should be excluded from this therapy by daily detection of triglycerides.

In malnutrition lipoprotein lipase activity in the liver and the beta-lipoprotein concentration in serum are reduced. The lipolysis is increased. One suspected a reduction of fat elimination in such patients. In 10 malnourished patients with a mean body weight of 73% ideal body weight an intravenous fat tolerance test was performed. The elimination rate was in mean 5.77%/min, that is in the normal range. Studies with radioactive triglycerides showed a metabolization of 30% of infused fat during 24 hours. These results were confirmed by measurements of gas exchange. Energy expenditure and nitrogen balance in malnourished patients correlate with the energy intake but not with the amount of fat in the parenteral nutrition. That could be confirmed in a prospective randomized study in 8 malnourished patients. The carbohydrate oxydation provided 70% to 80% of total energy expenditure independent from the dosage of fat in these patients. The minimum of fat needed in total parenteral nutrition to avoid essential fatty acid deficiency is 100 g per week. The tolerable maximum dose ist not known. In 10 malnourished patients with a mean time of 36 days of parenteral nutrition a dosage of 2.5 g/kg X d-1 was well tolerated and no side effects were seen. In 3 of these patients a previous cholostasis improved during parenteral nutrition.