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Biomedical subjects

H Lochs

Publications and source records attributed to H Lochs.

At least 37 records · Page 2Linked to original sources

Glutamine-enriched total parenteral nutrition in patients with inflammatory bowel disease.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Acute Disease↗

Does passage of a patency capsule indicate small-bowel patency? A prospective clinical trial?

BACKGROUND AND STUDY AIMS: At many centers wireless capsule endoscopy (WCE) without prior radiographic examination to rule out relevant strictures is considered to be contraindicated in suspected obstructive small-bowel disease. However, the accuracy of radiography in this situation has often been questioned. The purpose of this prospective study was to investigate the feasibility and safety of the recently developed patency capsule, and its predictive value regarding the clinical relevance of radiographic small-bowel strictures. PATIENTS AND METHODS: 22 patients with suspected obstructive small-bowel disease and/or radiological evidence of small-bowel strictures underwent a patency capsule examination. Intact passage, patient experience of pain, and capsule disintegration were correlated with radiographic findings, clinical variables, and outcome. RESULTS: 13 patients passed an intact capsule without complaints, despite radiographically observed small-bowel stenosis; the subsequent video capsule examination was uneventful in all. In nine patients either intact passage was painful or the capsule disintegrated; in one of these, impaction of an intact capsule led to an ileus and emergency surgery. The type of capsule passage did not correlate with radiographic presence of a stricture, underlying diagnosis, or previous surgery. There was a statistically significant correlation between outcome (surgery performed or recommended) and occurrence of painful capsule passage and disintegration ( P < or = 0.05). CONCLUSIONS: Painless egestion of an intact patency capsule indicates safety of WCE. Patients without obstructive symptoms require neither small-bowel radiography nor a patency capsule study prior to WCE. Disintegration of the patency capsule or painful passage seems to be associated with a clinically relevant small-bowel stricture and with a high probability of surgery.

Adult↗

Small bowel involvement in Crohn's disease: a prospective comparison of wireless capsule endoscopy and computed tomography enteroclysis.

BACKGROUND: Wireless capsule endoscopy (WCE) offers endoscopic access to the small bowel and may therefore change diagnostic and therapeutic strategies in small bowel diseases. AIM: The aim of this prospective study was to validate the gain in information and therapeutic impact of WCE in patients with Crohn's disease. METHODS: Fifty six consecutive patients with Crohn's disease underwent computed tomography (CT) enteroclysis, and if stenoses <10 mm were excluded, WCE was carried out. RESULTS: In 15 patients (27%), WCE could not be performed due to strictures detected by CT enteroclysis. From the other 41 patients, jejunal or ileal lesions were found in 25 patients by WCE compared with 12 by CT enteroclysis (p=0.004). This gain in information was mainly due to detection of small mucosal lesions such as villous denudation, aphthoid ulcerations, or erosions. Both methods were not significantly different in the detection of lesions in the terminal/neoterminal ileum (WCE 24 patients, CT enteroclysis 20 patients). Therapy was changed due to WCE findings in 10 patients. Consecutively, all of them improved clinically. CONCLUSIONS: Capsule endoscopy improves the diagnosis of small bowel Crohn's disease. This may have significant therapeutic impact.

Adult↗

Bacterial biofilm within diseased pancreatic and biliary tracts.

BACKGROUND: Bacterial community structures in human pancreatic and biliary tracts were evaluated. METHODS: Gall bladder stones from 153 patients, 20 gall bladder walls, six common duct stones, 52 biliary stents, 21 duodenal biopsies, nine pancreatic duct biopsies, and five bile ducts were investigated using fluorescence in situ hybridisation (FISH) with ribosomal RNA targeted Cy3/Cy5 (carbocyanine) labelled oligonucleotide probes. RESULT: Duodenal, gall bladder, and bile duct walls were free of bacteria. A dense multispecies bacterial biofilm was present within the pancreatic duct of patients with calcific pancreatitis and within biliary stents, irrespective of diagnosis. The concentration, density, and amenability of the biofilm to FISH and DNA staining declined progressively with the grade of stent occlusion. The lowest detectable bacterial concentrations were found by FISH in completely occluded stents and brown/mixed gall stones. Bacteria were not detectable with FISH in cholesterol gall stones. CONCLUSIONS: A wide range of different branches and groups of bacteria participate in the development of biofilms on the surfaces of foreign bodies, such as biliary stents, mixed gall stones, or calcific pancreatic ducts, but not on the surface of pure cholesterol gall stones. Occlusion of stents leads to progressive extinction of the biofilm and mummification of its components. Deposition of cholesterol or other substances within the biofilm matrix may be a novel mechanism of host defence against bacteria present in these biofilms.

Bacteria↗

Mutations in the NOD2/CARD15 gene in Crohn's disease are associated with ileocecal resection and are a risk factor for reoperation.

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.

Adolescent↗

[Hypophyseal ACTH-cell carcinoma after several surgical interventions and radiotherapy].

HISTORY AND ADMISSION FINDINGS: A 56-year-old woman was admitted to our hospital with headache, especially on the left temporal side, dizziness and exercise intolerance. She had been operated three times and radiotherapy once because of pituitary adenoma with intermittend hypercortisolism. The clinical examination was without abnormal findings apart from left temporal pain on pressure on the top of the skull. INVESTIGATIONS: Blood tests were entirely normal. At cranial magnet resonance imaging (cMRI) a left temporal tumor of 10 mm diameter was diagnosed. TREATMENT AND COURSE: The first histological study of the excized lesion could not clarify the diagnosis completely. Because of a local recurrent tumor of 20 mm, a second operation was necessary two months later. Due to structural and immunohistological similarities this tumor was identified as a metastasis of a pituitary ACTH-cell carcinoma. The patient was given adjuvant stereotactic radiotherapy. Two years after the treatment, no tumor recurrence was seen by cMRI. CONCLUSION: Carcinomas of the pituitary are very rare. They can be diagnosed only by their metastases. The pathogenesis is still unclear. It is debatable, whether surgery and/or X-ray therapy in the past may influence tumor development.

Adenoma, Chromophobe↗

Keratin 8 Y54H and G62C mutations are not associated with inflammatory bowel disease.

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.

Adolescent↗

A sensitive noninvasive method for monitoring successful liver-directed gene transfer of the low-density lipoprotein receptor in Watanabe hyperlipidemic rabbits in vivo.

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.

Adenoviridae↗

Endoscopic injection of mitomycin adsorbed on carbon particles for advanced esophageal cancer: a pilot study.

BACKGROUND AND STUDY AIMS: Patients with advanced, unresectable esophageal carcinoma have an extremely poor prognosis, with dysphagia being the major problem. The aim of this prospective pilot study was to evaluate the efficacy of local injections of mitomycin adsorbed onto activated carbon particles (MMC-CH) in advanced unresectable esophageal squamous-cell carcinoma. The primary outcome parameter was survival time; secondary parameters were dysphagia and quality of life. PATIENTS AND METHODS: Ten consecutive patients with stage IV esophageal carcinoma (age: median 58, range 32 - 78), median tumor length 11 cm (range 5 - 15) received four weekly injections of 15 mg (10 ml) MMC-CH into the endoscopically visualized tumor, via a 5-mm sclerotherapy needle. The tumor stage, symptom score, and quality of life (measured using the Karnofsky index) were assessed before and after therapy and every 2 months thereafter. RESULTS: The median survival time after MMC-CH therapy was 16 weeks (95 % CI, 11.7 to 20.4). Dysphagia was reduced ( P < 0.001) in parallel with the reduction in the tumor mass ( r = 0.82, P = 0.01). The Karnofsky index ( P < 0.01) also improved after MMC-CH treatment. MMC-CH was well tolerated, and no side effects were observed. CONCLUSIONS: Endoluminal MMC-CH therapy appears to be an effective, inexpensive, and well-tolerated treatment for unresectable advanced squamous-cell esophageal carcinoma.

Adsorption↗

Covered transjugular intrahepatic portosystemic stents maintain lower portal pressure and require fewer reinterventions than uncovered stents.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Adult↗

Pseudoallergic reactions in chronic urticaria are associated with altered gastroduodenal permeability.

BACKGROUND: In a subgroup of patients with chronic urticaria (CU) the disease is caused by pseudoallergic reactions to food. The aim of this study was to investigate whether disturbances of the gastrointestinal barrier function play a role in the pathomechanism of the disease. METHODS: In 55 patients with CU gastrointestinal permeability was measured with an in vivo triple-sugar-test before and after 24 days of a diet low in pseudoallergens. Sucrose served as marker for gastroduodenal permeability, lactulose/mannitol ratio for intestinal permeability. RESULTS: Basal gastroduodenal and intestinal permeability were significantly higher in patients with urticaria as compared to controls. In 29 of the 55 patients skin symptoms decreased or completely disappeared during the diet (responders). Compared to nonresponders (n = 26), responders had a significantly higher gastroduodenal permeability before treatment (0.36 +/- 0.04 vs 0.15 +/- 0.01% sucrose; P < 0.001), which decreased after the diet (0.17 +/- 0.02; P < 0.001). The number of patients with Helicobacter pylori infections did not differ between the two groups. CONCLUSIONS: The results indicate that in a subgroup of patients with CU and pseudoallergy an impaired gastroduodenal barrier function may be of pathophysiological importance. The underlying mechanisms seem to be independent of H. pylori infection.

Adult↗

Splanchnic oxygen transport, hepatic function and gastrointestinal barrier after normothermic cardiopulmonary bypass.

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 < 0.0125) and arterial lactate concentrations increased. The splanchnic lactate uptake paralleled the lactate concentration. After but not during CPB an increase of systemic oxygen consumption was observed. The MEGX test values decreased on the first day after surgery. The ICG extraction was attenuated during the operation. The gastroduodenal and the intestinal permeability increased significantly postoperatively (P < 0.002, respectively, P < 0.001). There was no correlation between these findings and the duration of CPB. There was a significant correlation of the intestinal permeability but not of the gastroduodenal permeability between the prior and after surgery values (P < 0.001). CONCLUSION: Increased oxygen consumption during CPB may indicate an inflammatory reaction due to the pump beginning in the splanchnic area or a redistribution of the splanchinc blood flow during the CPB. Normothermic CPB does not lead to a significant or prolonged reduction of liver function. Normothermic CPB causes an increase of gastrointestinal permeability. The intestinal barrier function prior to surgery was accountable for the degree of loss of intestinal barrier function following surgery.

Adult↗

Thalidomide for treatment of severe intestinal bleeding.

Apart from its anti-inflammatory activity, which has been used for the treatment of active Crohn's disease, thalidomide is also a potent inhibitor of angiogenesis. We therefore studied the effect of thalidomide in six patients with severe recurrent intestinal bleeding refractory to standard treatment (three patients with Crohn's disease (CD), three patients with obscure intestinal bleeding; mean of 56 blood transfusions within the last 24 months). Bleeding stopped within two weeks after the start of thalidomide in all patients. Haemoglobin normalised without further transfusions for the whole observation period (mean follow up 33 months) while patients needed a mean of 2.2 (CD) and 3.1 (obscure bleeding) blood units/month in the 12 months before treatment. After three months of thalidomide therapy, serum levels of vascular endothelial growth factor were strongly suppressed compared with pretreatment levels. (CD 818 (82) v 129 (86) pg/ml; obscure bleeding 264 (68) v 50 (25) pg/ml). All six patients reported transient fatigue. Peripheral neuropathy was observed in one patient with CD after nine months and was reversible after lowering the dose to 100 mg daily. These results indicate that thalidomide might be useful for patients with otherwise refractory intestinal bleeding.

Adult↗

Prevalence of malnutrition in 1760 patients at hospital admission: a controlled population study of body composition.

OBJECTIVE: Malnutrition, defined as low or excessive body weight, is associated with increased hospital length of stay and cost of care. The purpose of this study was to determine if fat-free mass (FFM) and body fat (BF) differed between patients at hospital admission in Geneva and Berlin and healthy volunteers, and if there is a difference in the prevalence of low FFM (percentile P<10) and high BF (percentile P>90) between patients and volunteers. METHODS: In total, 1760 patients (Geneva: 525 men, 470 women; Berlin: 397 men, 368 women) were evaluated for malnutrition by BMI, serum albumin, and FFM and BF, determined by bioelectrical impedance analysis (BIA), and compared to 1760 healthy volunteers matched for age and height, and further compared to FFM and BF percentiles, previously determined in 5225 healthy adults. RESULTS: The prevalence of FFM P<10 was greater in patients than controls. The prevalence of albumin<35 g/l (14.9% and 11.2% in Geneva and Berlin patients, respectively) and BMI<20.0 kg/m(2) was lower than the prevalence of low FFM (31.3% and 17.3%, respectively). The prevalence of high BF in Berlin patients was three-fold the prevalence of volunteers. Twelve and twenty percent of Geneva and Berlin patients, respectively, with normal BMI had high BF, compared to 4% of volunteers. CONCLUSIONS: Geneva and Berlin patients had lower FFM and higher BF than age-and height-matched volunteers and a higher prevalence of low FFM and high BF. Serum albumin and BMI underestimated the prevalence of malnutrition in patients at hospital admission. Body composition measurements identified patients with low FFM and low or high BF reserves.

Adipose Tissue↗

Replacement of conventional glucocorticoids by oral pH-modified release budesonide in active and inactive Crohn's disease: results of an open, prospective, multicenter trial.

Glucocorticosteroids (GCS) are established in the treatment of active Crohn's ileitis and ileocolitis. Recently, the topical steroid budesonide was found to be effective in untreated patients with Crohn's disease (CD) causing less side effects than conventional GCS. No clinical data have been reported about the effects of switching from conventional GCS to budesonide in terms of side effects and disease activity. The primary aim of this study was to evaluate the development of side effects after switching from conventional GCS treatment to Eudragit L-coated budesonide (pH-modified release formulation) in patients taking 5-30 mg prednisolone equivalent per day for at least two weeks. In all, 178 patients with active CD (N = 88) or CD in remission during GCS treatment (N = 90) were included. Conventional GCS treatment was tapered down during a maximum of three weeks, with simultaneous intake of 3 x 3 mg budesonide. Thereafter, patients received 3 x 3 mg budesonide alone for six weeks. GCS-related side effects, disease activity and adverse events were documented at study entry and after 0, 2, 4, and 6 weeks of budesonide treatment. The percentage of patients with GCS-related side effects decreased from 65.2% (intention-to-treat-population) at entry to 43.3% (P < 0.0001) at the end of the trial. The total number of GCS-related side effects decreased significantly from 269 to 90. Of the patients who entered the study with active disease under conventional GCS therapy, 38.6% were in remission at the end of the study. Of the patients who entered the study with CD in remission, 78% stayed in remission after switching from conventinal GCS to budesonide. In conclusion, switching from conventional GCS treatment to budesonide leads to a significant reduction of GCS related side effects in patients with CD without causing rapid deterioration of the disease.

Administration, Oral↗