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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 Malnutrition is a common problem in patients with digestive disease and is associated with impaired outcome. Objective We investigated the effect of a three-month post-hospital nutritional intervention with high protein and energy supplements on body composition, muscle function and quality of life (QoL) in malnourished GI patients. Patients and intervention Eighty malnourished patients with benign digestive disease were randomized to receive either oral nutritional supplements (ONS) for three months in addition to dietary counselling (DC) (ONS patients) or only dietary counselling (DC patients). Methods Nutritional status was determined with the subjective global assessment, body composition by bioelectrical impedance and anthropometry, muscle function with hand-grip strength and peak flow. QoL was assessed by the 36-item short-form questionnaire. Results Age, body cell mass (BCM), muscle function, gender distribution and QoL did not differ between ONS patients (n=38) and DC patients (n=42) at baseline. Body weight and BCM improved significantly in both groups after three months. However, hand-grip strength (26.1±11.3–31.5±10.1 kg, p

Objective The calculation of body composition using bioelectrical impedance analysis is difficult in the elderly because most equations have been found to be inadequate, especially in the malnourished elderly. We therefore evaluated the use of bioelectrical impedance vector analysis in elderly nursing home residents. Methods One hundred twelve nursing home residents were included in the study (34 men, 78 women, age 85.1 y, age range 79.1–91.4 y). Nutritional status was determined by the Mini Nutritional Assessment (MNA), functional status was assessed by handgrip strength, knee extension strength, and Barthel’s index, and bioelectrical impedance analysis was performed using Nutriguard M (Data Input, Darmstadt, Germany). Results Twenty-two nursing home residents were classified as well nourished (MNA I), 80 were considered to be at nutritional risk (MNA II), and 10 were classified as malnourished (MNA III). Handgrip strength, knee extension strength, and Barthel’s index were lower in MNA II and MNA III than in MNA I. Phase angle also decreased significantly with the MNA (4.0, 3.8–4.7°; 3.7, 3.3–4.3°; and 2.9, 2.6–3.5°). There was a significant displacement of the mean vector in MNA II and MNA III compared with MNA I. Conclusion The bioelectrical impedance vector analysis resistance/reactance graph could represent a valuable tool to assess changes in body cell mass and hydration status in elderly nursing home residents.

Objective The purpose of this study was to determine the efficacy of standard treatment with oral metronidazole in the eradication of the bacterial vaginosis biofilm. Study Design We conducted an interventional follow-up study in which 18 patients with bacterial vaginosis were treated with oral metronidazole during 1 week and subsequently had a single random follow-up assessment at 1-week intervals, up to 5 weeks, with 3 patients representing each point in time. Follow-up assessment included conventional scoring of the vaginal microflora and determination of bacterial biofilm characteristics on a vaginal biopsy through bacterial 16/23S recombinant DNA–based fluorescence in-situ hybridization. Results Although all patients recovered, we consistently observed the resurgence with treatment cessation of a dense and active bacterial biofilm on the vaginal mucosa, primarily consisting of Gardnerella vaginalis and Atopobium vaginae . Conclusion A large reservoir of the core bacteria to bacterial vaginosis persists as a biofilm after metronidazole treatment.

The role of the single nucleotide polymorphisms (SNPs) on positions 2677GT/A and 3435CT of the multi-drug-resistance gene 1 (MDR1) in inflammatory bowel disease (IBD) remains unclear.To further elucidate the potential impact of MDR1 two-locus genotypes on susceptibility to IBD and disease behaviour.Three hundred eighty-eight German IBD patients [244 with Crohn's disease (CD), 144 with ulcerative colitis (UC)] and 1,005 German healthy controls were genotyped for the two MDR1 SNPs on positions 2677GT/A and 3435CT. Genotype-phenotype analysis was performed with respect to disease susceptibility stratified by age at diagnosis as well as disease localisation and behaviour.Genotype distribution did not differ between all UC or CD patients and controls. Between UC and CD patients, however, we observed a trend of different distribution of the combined genotypes derived from SNPs 2677 and 3435 (chi(2) = 15.997, df = 8, p = 0.054). In subgroup analysis, genotype frequencies between UC patients with early onset of disease and controls showed significant difference for combined positions 2677 and 3435 (chi(2) = 16.054, df = 8, p = 0.034 for age at diagnosisor=25, lower quartile). Herein the rare genotype 2677GG/3435TT was more frequently observed (odds ratio = 7.0, 95% confidence interval 2.5 - 19.7). In this group severe course of disease behaviour depended on the combined MDR1 SNPs (chi(2) = 16.101, df = 6, p = 0.017 for age at diagnosisor=25). No association of MDR1 genotypes with disease subgroups in CD was observed.While overall genotype distribution did not differ, combined MDR1 genotypes derived from positions 2677 and 3435 are possibly associated with young age onset of UC and severe course of disease in this patient group.

This review focuses on the studies investigating the prognostic implications of disease-related malnutrition. Malnutrition is a common problem in patients with chronic or severe diseases. Prevalence of hospital malnutrition ranges between 20% and 50% depending on the criteria used in order to determine malnutrition and the patient's characteristics. Furthermore, nutritional status is known to worsen during hospital stay which is partly due to the poor recognition by the medical staff and adverse clinical routines. Studies have repeatedly shown that clinical malnutrition however has serious implications for recovery from disease, trauma and surgery and is generally associated with increased morbidity and mortality both in acute and chronic diseases. Length of hospital stay is significantly longer in malnourished patients and higher treatment costs are reported in malnutrition. Since it has been demonstrated that proper nutritional care can reduce the prevalence of hospital malnutrition and costs, nutritional assessment is mandatory in order to recognise malnutrition early and initiate timely nutritional therapy.

Suprasellar germinomas are rare intracranial neoplasms, which mainly occur in children and adolescents and manifest with endocrine symptoms and/or compression syndromes.The clinical, hormonal and morphological findings as well as treatment and complications were investigated in seven patients (six male, one female) with germinomas.Mean age at diagnosis was 19.7 years (range 15-32 years). First disease-related symptoms were diabetes insipidus (three patients), loss of libido (two patients), pseudopubertas praecox (one patient), and dwarfism (one patient). However, decisive symptoms leading to final diagnosis were visual disturbances (five patients), pubertas tarda (one patient), and hypogonadism (one patient). All patients were treated by transcranial radiation with a dose of 40-54 Gy. One patient received additional chemotherapy with cisplatin, etoposide, and ifosfamide (PEI). Patients were followed up for 14.6 years (range 7-27 years). Intracranial and pulmonary relapses were observed in two patients. Panhypopituitarism and diabetes insipidus were seen in all patients after treatment. Two patients suffered from loss of vision, two further patients from unilateral amaurosis. One patient developed epilepsy and persistent cognitive impairment. Long-term follow-up shows that two patients died from recurrent disease and decompensated liver cirrhosis, respectively. The other patients are long-term survivors. Full social integration with employment was possible in one case.Suprasellar germinomas cause endocrine symptoms during early tumor stages, however, diagnosis is generally established when ocular symptoms related to tumor compression are already present. Long-term survival is characterized by panhypopituitarism, diabetes insipidus and, partly, ocular or cerebral defects.

Crohn's disease (CD) is a multifactorial disorder of unknown cause. Outstanding progress regarding the pathophysiology of CD has led to the development of innovative therapeutic concepts. Numerous controlled trials have been performed in CD over the last years. However, many drugs have not been approved by regulatory authorities due to lack of efficacy or severe side effects. Therefore, well-known drugs, including 5-ASA, systemic or topical corticosteroids, and immunosuppressants such as azathioprine, are still the mainstay of CD therapy. Importantly, biologicals such as infliximab have shown to be efficacious in problematic settings such as fistulizing or steroid-dependent CD. This review is intended to give practical guidelines to clinicians for the conventional treatment of CD. We concentrated on the results of randomized, placebo-controlled trials and meta-analyses, when available, that provide the highest degree of evidence. We provide evidence-based treatment algorithms whenever possible. However, many clinical situations have not been answered by controlled clinical trials and it is important to fill these gaps through expert opinions. We hope that this review offers a useful tool for clinicians in the challenging treatment of CD.

Introduction: Copper overload due to a defect in the ATPase 7B mediated copper excretion within hepatocytes produces the phenotype of Wilson disease. The overload of hepatocytes with copper results in necrotic liver cells and is accompanied by a high concentration of blood copper levels. That occurs to be the reason for increasing neurological copper concentration. Although copper is linked to oxidation, there are no data on the direct copper related effects in human brain cells. Aim: To test the copper induced changes in protein oxidation in human astrocyte like cells. Methods: We used U87 cells as model for human astrocytes. Cells were treated with increasing concentrations of copper(II)-chloride in Dulbeccos minimal essential medium. Subsequently, at different time points we investigated: cellular growth, cellular survival under copper treatment, the concentration of oxidized tryptophane in GADPH in vitro as well as the carbonyl concentration and the concentration of oxidized proteins in vivo in U87 glial cells. Results: The viability of cells decreased with both increasing copper concentration and duration of treatment. The concentration of oxidized proteins was directly correlated to the increase of copper concentration and duration of exposure. Conclusion: These observations demonstrate the similarities between copper treatment and treatment with other commonly used oxidants, including hydrogen peroxide. Furthermore, the vulnerability of astrocytes towards copper exposure could be demonstrated. Therefore, these data give further insights into understanding of copper metabolism, which in turn is important to reveal the exact pathological mechanism in copper related diseases such as Wilson disease.

1. Aliment Pharmacol Ther. 2006 Apr 15;23(8):1117-25. Antibiotic treatment of Crohn's disease: results of a multicentre, double blind, randomized, placebo-controlled trial with rifaximin. Prantera C, Lochs H, Campieri M, Scribano ML, Sturniolo GC, Castiglione F, Cottone M. Operative Unit of Gastroenterology, St Camillo-Forlanini Hospital, Rome, Italy. prantera@tin.it BACKGROUND: Clinicians often employ antibiotics in Crohn's disease. Rifaximin is active against bacteria frequently found in the intestinal mucosa of Crohn's disease patients. AIM: To evaluate the difference in efficacy between once and twice/daily oral administration of rifaximin and placebo in the treatment of active Crohn's disease. METHODS: We enrolled 83 patients with mild-to-moderate Crohn's disease and randomized to three treatments for 12 weeks: Group A (rifaximin 800 mg o.d. + placebo), Group B (rifaximin 800 mg b.d.) and Group C (placebo b.d.). RESULTS: Clinical remission was achieved by 52% of Group B, 32% (A) and 33% (C). Clinical response was seen in 67% (B), 48% (A) and 41% (C), without reaching a statistically significant difference. Treatment failures were: 4% (B), 12% (A) and 33% (C), (P = 0.010). Remission and response rates of rifaximin 800 mg b.d. were significantly higher than those of placebo and rifaximin 800 mg o.d. in patients with elevated C reactive protein values (P < 0.05). CONCLUSIONS: Rifaximin 800 mg b.d. was superior to placebo in inducing clinical remission of active Crohn's disease. Although this difference was not statistically significant, the number of the failures in the placebo group was significantly higher than those who received rifaximin 800 mg b.d. PMID: 16611272 [PubMed - indexed for MEDLINE]

Malnutrition is frequently observed in chronic and severe diseases and associated with impaired outcome. In Germany general data on prevalence and impact of hospital malnutrition are missing.Nutritional state was assessed by subjective global assessment (SGA) and by anthropometric measurements in 1,886 consecutively admitted patients in 13 hospitals (n=1,073, university hospitals; n=813, community or teaching hospitals). Risk factors for malnutrition and the impact of nutritional status on length of hospital stay were analyzed.Malnutrition was diagnosed in 27.4% of patients according to SGA. A low arm muscle area and arm fat area were observed in 11.3% and 17.1%, respectively. Forty-three % of patients 70 years old were malnourished compared to only 7.8% of patients30 years. The highest prevalence of malnutrition was observed in geriatric (56.2%), oncology (37.6%), and gastroenterology (32.6%) departments. Multivariate analysis revealed three independent risk factors: higher age, polypharmacy, and malignant disease (all P0.01). Malnutrition was associated with an 43% increase of hospital stay (P0.001).In German hospitals every fourth patient is malnourished. Malnutrition is associated with increased length of hospital stay. Higher age, malignant disease and major comorbidity were found to be the main contributors to malnutrition. Adequate nutritional support should be initiated in order to optimize the clinical outcome of these patients.

OBJECTIVE: Bacterial vaginosis is a common infectious disorder. Although known since ancient times, little progress has occurred in identifying causal factors. Our aims were to study the bacterial community structure and the spatial organization of microbiota on the epithelial surfaces of vaginal biopsy specimens. METHODS: We investigated the composition and spatial organization of bacteria associated with the vaginal epithelium in biopsy specimens from 20 patients with bacterial vaginosis and 40 normal premenopausal and postmenopausal controls using a broad range of fluorescent bacterial group-specific rRNA-targeted oligonucleotide probes. RESULTS: Bacterial vaginosis was associated with greater occurrence and higher concentrations of a variety of bacterial groups. However, only Gardnerella vaginalis developed a characteristic adherent biofilm that was specific for bacterial vaginosis. CONCLUSION: A biofilm comprised of confluent G vaginalis with other bacterial groups incorporated in the adherent layer is a prominent feature of bacterial vaginosis. (Obstet Gynecol 2005;106:1013–23) LEVEL OF EVIDENCE: II-2

Studies in animal models of inflammatory bowel disease (IBD) suggest that supplementation of total parenteral nutrition with glutamine (gln), a conditionally essential amino acid in catabolic conditions, increases gln plasma concentrations, reduces intestinal damage, improves nitrogen balance and may improve the course of the disease. However, human data supporting this assumption are missing.A total of 24 consecutive patients with an acute exacerbation of IBD (19 Crohn's disease; five ulcerative colitis) and scheduled for total parenteral nutrition (TPN) (7 days) were randomised. Parallel to a standardised anti-inflammatory therapy, the patients received either a TPN with 1.5 g/kg body weight of a standard amino acid or an isonitrogenic, isocaloric TPN with 1.2 g/kg body weight of a standard amino acid and 0.3 g/kg L-alanine-L-glutamine. Primary end points were gln plasma concentrations and intestinal permeability assessed by urinary lactulose and D-xylose ratio.Gln plasma levels did not differ significantly in either group throughout the study. Intestinal permeability did not change within 7 days either with or without gln supplementation (Delta-lactulose/xylose ratio: 0.01+/-0.05 (gln+) vs 0.02+/-0.1 (gln-)). The observed changes in inflammatory and nutritional parameters, and also disease activity, length of TPN and hospital stay, were independent of glutamine substitution. Five (41%) patients in the gln+ group and three (25%) patients in the gln- group needed surgical intervention.Although limited by the sample size, these results do not support the hypothesis that glutamine substitution has an obvious biochemical or clinical benefit in patients with active IBD scheduled for total parenteral nutrition.

Background Levetiracetam is an antiepileptic drug approved for use as adjunctive therapy in adults with partial-onset seizures. We sought to investigate possible changes in the pharmacokinetics of levetiracetam and its metabolite ucb L057 in patients with liver cirrhosis, who may require dose adjustments. Methods A single dose of levetiracetam was administered to 5 healthy subjects and to patients with Child-Pugh class A (n = 5), B (n = 6), or C (n = 5) alcohol-induced cirrhosis. The pharmacokinetics of levetiracetam and ucb L057 was measured and correlated with biochemical liver function parameters, with creatinine clearance, and with kinetics of caffeine, lidocaine, and D-sorbitol as probes for specific liver functions. Results Dynamic liver function tests revealed a deterioration of liver function. The pharmacokinetics of levetiracetam and its metabolite did not differ between healthy subjects and those with class A or B cirrhosis. However, in patients with class C cirrhosis, levetiracetam total clearance was reduced by 57% (90% confidence interval [CI], 43%-67% P < .001). The geometric mean ratio of the area under the plasma concentration-time curve for levetiracetam, Child-Pugh class C versus control, was 2.41 (90% CI, 1.80–3.23), and the geometric mean of the half-life ratio was 2.27 (90% CI, 1.74–2.97). This was explained by the deterioration of renal function in patients with severe hepatic disease. Conclusions In pharmacokinetic studies of hepatic impairment, including all classes of cirrhosis may be more revealing than including only selected classes of liver failure. No dose adjustment of levetiracetam is necessary in patients with mild to moderate liver impairment; however, patients with severe cirrhosis should initially receive only half of the commonly recommended dose. Clinical Pharmacology & Therapeutics (2005) 77, 529–541; doi: 10.1016/j.clpt.2005.02.003

Background The proteolysis-inducing factor (PIF) was identified as a tumour product in various gastrointestinal cancers. A previous study in pancreatic cancer patients suggested PIF expression as a tumour marker, which is not related to tumour size. We hypothesized that PIF could be a useful marker to exclude benign pancreatic tumors, as chronic pancreatitis with a pancreatic mass. Methods Urine of patients with a pancreatic mass of uncertain malignancy was investigated for PIF expression by Western blot. Sufficient urine protein for analysis was available in 59 patients. The diagnosis was established by histology in 54 patients and by follow up in five patients with chronic pancreatitis. In addition, serum CA19-9 was measured. Results The sensitivity (specifity) for the detection of a malignant pancreatic tumour was 90% (75%) and 54% (71%) for CA19-9 and PIF, respectively. The sensitivity (specifity) for the distinction of pancreatic cancer from chronic pancreatitis was 89% (80%) and 57% (63%) for CA19-9 and PIF, respectively. Conclusion Evaluation of PIF in urine is of no diagnostic value in patients with a pancreatic mass of unknown malignancy.

Background Patients with neuroendocrine tumors (NET) of the small bowel often present with metastatic disease, and localization of the primary tumor still is a diagnostic challenge. Wireless capsule endoscopy (WCE) is an established method that improves the diagnostic evaluation of diseases of the small intestine. Objective The aim of this study was to determine the diagnostic accuracy of WCE in imaging neuroendocrine tumors of the small bowel in these patients. Design We retrospectively compared the findings of capsule endoscopy to the findings of CT enteroclysis in patients with histopathological confirmation of NET. Patients Eight patients with newly established diagnosis of metastatic NET were included. Interventions All patients underwent CT enteroclysis and wireless capsule endoscopy within a maximum of 2 weeks. Main Outcome Measurements Number of primary tumors detected. The results of surgery were used as a gold standard for both methods. Results CT enteroclysis detected the primary tumor in 4 of 8 patients whereas WCE found the primary in 3 patients. On the contrary, CT enteroclysis provided more false-positive results. Limitations Frequent extraluminal tumor growth. Conclusions In patients with NET, wireless capsule endoscopy may be helpful in individual cases but the general diagnostic value of this method may be limited due to frequent extraluminal growth of these tumors.

Summary Introduction Malnutrition is associated with a higher morbidity resulting in an increased need for medical resources and economic expenses. In order to ensure sufficient nutritional care it is mandatory to identify the effect of malnutrition and nutritional care on direct cost and reimbursement. The primary aim of this study was to evaluate the economic effect of a nutritional screening procedure on the identification and coding of malnutrition in the G-DRG system. Methods All G-DRG relevant parameters of 541 consecutive patients at a gastroenterology ward were documented. Moreover, all patients were screened for malnutrition by a dietician according to the subjective global assessment (SGA). Patients were then grouped into the appropriate G-DRG and the effective cost weight (CW) was calculated. Results Ninety-two of 541 patients (19%) were classified malnourished (SGA B or C). Recognition of malnutrition increase from 4% to 19%. Malnourished patients exhibited a significantly increased length of hospital stay (7.7±7 to 11±9, P 0.0001 ). In 26/98 (27%) patients, the coding of malnutrition was considered relevant by grouping and resulted in a rise of DRG benefit. Mean case mix value and patients’ complexity and comorbidity level (PCCL) increased after including malnutrition in the codification (CV 1.53±2.9 to 1.65±2.9, P = 0.001 and PCCL 2.69±1.4 to 3.47±0.82, P 0.0001 ). The reimbursement increase by 360 €/malnourished patient or an additional reimbursement of 35280 € (8.3% of the total reimbursement for all patients of 423186 €). Nutritional support in a subgroup of 50 randomly selected patients resulted in additional costs of 10268 €. Forty-four of these patients (86%) were classified malnourished (32 SGA B and 12 SGA C). However, the subsequent reimbursement covered only approximately 75% of the expenses (7869 €), but did not include the potential financial benefits resulting from clinical interventions. Conclusion Malnourished patients can be detected with a structured assessment and documentation of nutritional status and this is partly reflected in the G-DRG/ICD 10 system. In addition to increasing direct health care reimbursement, nutritional screening and intervention has the potential to improve health care quality.

AIM: To analyse the impact of NOD2/CARD15 mutations on the clinical course of Crohn’s disease patients from an eastern European country (Hungary). METHODS: We investigated the prevalence of the three common NOD2/CARD15 mutations (Arg702Trp, Gly908Arg, 1007finsC) in 148 patients with Crohn’s disease, 128 patients with ulcerative colitis and 208 controls recruited from the University of Szeged, Hungary. In patients with Crohn’s disease, the prevalence of NOD2/CARD15 mutations was correlated to the demographical and clinical parameters. RESULTS: In total, 32.4% of Crohn’s disease patients carried at least one mutant allele within NOD2/CARD15 compared to 13.2% of patients with ulcerative colitis (P = 0.0002) and to 11.5% of controls (P

In approximately 25% of patients with acute or chronic pancreatitis the cause remains unclear. Despite progress in understanding so-called idiopathic pancreatitis, more diagnostic criteria are needed. We report on a patient who presented with jaundice, but without pain or fever. Under the assumption of pancreatic cancer the patient underwent hemipancreatoduodenectomy. Histological examination showed chronic sclerosing inflammation of the pancreas and bile ducts without any signs of malignancy. Ten weeks later he developed bilateral parotid swelling and recurrent bouts of fever. Again liver enzymes were elevated and unsuccessfully treated with antibiotics for bacterial cholangitis. Further biopsies from submandibular gland, lymph nodes and liver again showed chronic sclerosing inflammation with lymphoplasmacytic infiltration. For sicca symptoms the diagnosis of a primary Sjogren's syndrome was proposed. However, with corticosteroid treatment the patient improved remarkably but after tapering he relapsed. On the basis of established criteria, we diagnosed autoimmune pancreatitis with (1) diffuse swelling of the pancreas, (2) irregularities of the pancreatic duct, (3) lymphoplasmacytic infiltration, (4) response to corticosteroids, (5) hypergammaglobulinaemia, and (6) disproportionately raised IgG4. In addition, the patient fulfilled the criteria for secondary Sjogren's syndrome. Autoimmune pancreatitis may present as an isolated or syndromic disease. It is an autoimmune disorder of unknown cause and should be included in the differential diagnosis of pancreatic disorders.

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 variantwas detectablein 106 (91.4%) patients. Among 50 patients with negative H2 breath test, the c.1993+327Cvariantwas 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.

Background. Keratin 8 is a major component of intermediate filaments in single-layered epithelia of the gastrointestinal tract. Keratin 8 deficient mice display signs of colitis and diarrhoea characteristic for inflammatory bowel disease. Very recently, two keratin 8 mutations, Y54H and G62C, were identified. Aims. We investigated if these keratin 8 missense mutations were associated with inflammatory bowel disease. Patients. In total, 217 German patients with Crohn’s disease, 131 German patients with ulcerative colitis, and 560 German control subjects were enrolled in this study. Methods. Samples were analysed by PCR amplification and subsequent melting curve analysis using fluorescence resonance energy transfer probes. Results. The G62C mutation was detected in five (2.3%) patients presenting with Crohn’s disease and in three (2.3%) with ulcerative colitis. In comparison, 9 (1.6%) out of 560 controls were heterozygous for this mutation. No patient or control was homozygous for this mutation. Patients carrying one mutant allele did not show any noticeable characteristics in their corresponding phenotype. In contrast, the Y54H mutation was observed in neither any of the 348 patients with inflammatory bowel disease nor in any control subject. Conclusions. Our data indicate that both keratin 8 mutations, G62C and Y54H, do not play a relevant pathogenic role in inflammatory bowel disease.

Non-Alcohol Induced Steatohepatitis in Non-Obese Patients: Treatment With Ursodeoxycholic Acid

Wilson disease (WD) is a rare inherited autosomal recessive disorder caused by a defect in a metal transporting P-type ATPase, resulting in copper overload in various tissues and cells. The aim was to assess both the phenotype in Brazilian WD patients and the corresponding ATP7B genotype. Sixty subjects belonging to 46 pedigrees diagnosed as WD were included in this study. Direct sequencing of all 21 exons within ATP7B and their flanking introns was performed. Demographic, clinical, laboratory and histopathological data at the time of diagnosis were obtained. We identified twenty-five mutations, twelve of them reported for the first time. The c.3402delC mutation had the highest allelic frequency (30.8%), followed by the c.2123T>C (p.L708P) (16.7%). Exons 8 and 15 were the site of 62.5% of the mutations. The common European mutation c.3207C>A (p.H1069Q) was not present at all. Phenotype varied greatly among individuals with the same ATP7B genotype. Our data confirm the heterogeneity of ATP7B genotype in Brazilian WD patients. The mutational spectrum is compatible with the Brazilian history of Mediterranean immigration; however, new mutations, and different frequencies and phenotype associated with the previously known mutations characterize this population. Exons 8 and 15 should be preferentially screened in WD cases from Brazil. Phenotype variation among subjects with the same ATP7B genotype suggests that modifying factors play an additional role in the pathogenesis of WD.

Objective Disease severity is considered an important risk factor for malnutrition in hospitalized patients. We investigated the effect of social factors and disease parameters on the development of malnutrition. Methods Nutritional state was assessed by the Subjective Global Assessment in 794 consecutively admitted patients in two hospitals in Berlin (n = 493, university hospital; n = 301, district hospital). The influences of age, sex, social status, life habits, and disease parameters on nutritional state was analyzed with univariate and multivariate logistic regression methods. Results Malnutrition was diagnosed in 22% of patients. Its prevalence was significantly higher in patients with malignant than with benign diseases (odds ratio [OR] = 1.568, P < 0.05) and in patients with multiple prescriptions (OR = 1.154, P < 0.001), but no difference was found between medical or surgical patients. The strongest risk factors for malnutrition in univariate analysis were age older than 60 y (OR = 2.861, P < 0.001), living alone (OR = 1.769, P = 0.002), and achieving a lower level of education (OR = 1.589, P < 0.05). Therefore, multivariate analysis was performed after stratification for age. Demonstrated independent additional risk factors were polypharmacy (OR = 2.367, P < 0.001) and malignant disease (OR = 4.114, P < 0.001) in young patients and polypharmacy (OR = 1.109, P < 0.002) and living alone (OR = 1.830, P = 0.008) in patients 60 y and older. Conclusions These data show that patients who are older, less educated, and live alone are at high risk of developing malnutrition. Thus special attention should be given to these risk groups when evaluating nutritional status and nutritional support.

Noninvasive tools to quantitate transgene expression directly are a prerequisite for clinical gene therapy. We established a method to determine location, magnitude, and duration of low-density lipoprotein (LDL) receptor (LDLR) transgene expression after adenoviral gene transfer into LDLR-deficient Watanabe hypercholesterolemic rabbits by following tissue uptake of intravenously injected (111)In-labeled LDL using a scintillation camera. Liver-specific tracer uptake was calculated by normalizing the counts measured over the liver to counts measured over the heart that represent the circulating blood pool of the tracer (liver/heart (L/H) ratio). Our results indicate that the optimal time point for transgene imaging is 4 h after the tracer injection. Compared with control virus-injected rabbits, animals treated with the LDLR-expressing adenovirus showed seven-fold higher L/H ratios on day 6 after gene transfer, and had still 4.5-fold higher L/H ratios on day 30. This imaging method might be a useful strategy to obtain reliable data on functional transgene expression in clinical gene therapy trials of familial hypercholesterolemia.