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Biomedical subjects

J Schoelmerich

Publications and source records attributed to J Schoelmerich.

At least 19 recordsLinked to original sources
PubMed2006

Soluble galectin-3 is a strong, colonic epithelial-cell-derived, lamina propria fibroblast-stimulating factor.

BACKGROUND: Colonic lamina propria fibroblasts (CLPFs) play an important role in the pathogenesis of fibrosis and strictures in Crohn's disease. AIM: To identify colonic epithelial cell (CEC)-derived factors that activate CLPFs. METHODS: Primary human CECs and CLPFs were isolated from control mucosa and interleukin 8 (IL8) of CLPF cultures was quantified by ELISA. Activation of nuclear factor kappaB (NF-kappaB) was shown, and translocation of NF-kappaB was inhibited by a dominant-negative IkappaB-expressing adenovirus. The major CLPF-activating and IL8 inducing protein was purified using fast-performance liquid chromatography (HiPrep 16/60 Sephacryl S-200 High Resolution Column) and sodium dodecyl sulphate gel electrophoresis. RESULTS: A considerable increase in IL8 secretion by CLPFs cultured in CEC-conditioned media compared with that in unconditioned media (155.00 (10.00) pg/microg v 1.434 (0.695) pg/microg) was found. The effect of CEC-conditioned media on CLPF IL8 secretion was NF-kappaB dependent. A protein or DNA array confirmed the involvement of NF-kappaB and activator protein-1. Purification of a candidate band isolated with the use of sodium dodecyl sulphate-polyacrylamide gel electrophoresis and subsequent sequencing showed soluble galectin-3 to be a strong CLPF-activating factor. Depletion of galectin-3 from conditioned media by immunoprecipitation abolished the CLPF stimulatory effect. CONCLUSIONS: Using a classical biochemical approach, soluble galectin-3 was identified as a strong activator of CLPFs produced by CEC. Galectin-3 induced NF-kappaB activation and IL8 secretion in these cells and may be a target for future therapeutic approaches to reduce or avoid stricture formation.

Adult↗
PubMed2006

[Cholangitis with subphrenic abscess after complicated cholecystectomy due to occluded plastic stents].

A 62-year-old lady presented with fever and abdominal pain. History revealed cholecystectomy two years ago due to cholecystolithiasis, complicated by perforation of the common bile duct, leading to hepaticojejunostomy, jejunocholedochostomy, endoscopic retrograde insertion of two plastic stents and percutaneous drainage of bilioma. The patient was lost to follow-up until she presented two years later in the emergency room. ERC was performed. Both stents were occluded. After extraction dirty bile popped out. Injection of contrast medium showed stones in the remaining common bile duct and dilatation of the intrahepatic bile ducts and the interposed jejunum. After stone extraction a subphrenic intrahepatic fluid collection became visible when injecting contrast medium in the intrahepatic bile ducts. Pus was aspirated. The abscess was drained with a nasobiliary tube. Antibiotics were given. Temperature and CRP normalized. The nasobiliary tube was removed when the biliary fluid was clear. Recovery was uneventful with complete resolution of symptoms.

Cholangitis↗
PubMed2006

[Esophagobronchial and esophagomediastinal fistula, pleural and pericardial effusion due to severe pseudodiverticulosis of the esophagus].

We describe the case of a patient who came to our hospital with deterioration of his general condition (especially with loss of weight) and progressive thoracic pain with dyspnea. We diagnosed a severe pseudodiverticulosis of the esophagus with esophagobronchial as well as esophagomediastinal fistulae. Furthermore, reactive pleural and pericardial effusions were shown and Candida was detected in a blood culture. By means of antibiotic therapy and esophageal stent implantation, a significant improvement of the clinical signs was achieved. Intramural pseudodiverticulosis of the esophagus is a rare and benign condition. Multiple triggers, for example, obstruction of the ducts due to shedding of epithelial cells, mucus, and/or submucous fibrosis are possible. Clinical signs are progressive dysphagia, caused by an inflamed stenosis of the esophagus.

Anti-Bacterial Agents↗
PubMed2006

[Surgical management of patients with peritoneal carcinomatosis of gastrointestinal origin].

Peritoneal carcinomatosis is found in approximately 15 % of patients with colorectal cancer during the course of their disease, and is associated with a poor prognosis. Even more patients with gastric cancer develop peritoneal seeding. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) have been introduced in the past decade and have led to 5-year survival rates of 30 to 40 % for selected patients with colorectal cancer and peritoneal carcinomatosis. These numbers have been demonstrated by many retrospective analyses and by prospective Phase II studies. The clinical assessment to select patients who will benefit from the combined therapy and achievement of complete macroscopic cytoreduction both play a crucial role. Less favourabale results have been achieved for patients suffering from stage IV gastric cancer with peritoneal seeding. Promising results were demonstrated for postoperative intraperitoneal chemotherapy following curative gastrectomy. Patients with hepatic, biliary and pancreatic cancers and peritoneal carcinomatosis do not benefit from cytoreductive surgery. There is a need for further multicentre, prospective trials analysing the use of hyperthermic intraperitoneal chemotherapy. They should be conducted in the specialised centres by interdisciplinary teams.

Antineoplastic Agents↗
PubMed2006

Monocyte chemoattractant protein-1 (MCP-1) inhibits the intestinal-like differentiation of monocytes.

Monocytes (MO) migrating into normal, non-inflamed intestinal mucosa undergo a specific differentiation resulting in a non-reactive, tolerogenic intestinal macrophage (IMAC). Recently we demonstrated the differentiation of MO into an intestinal-like macrophage (MAC) phenotype in vitro in a three-dimensional cell culture model (multi-cellular spheroid or MCS model). In the mucosa of patients with inflammatory bowel disease (IBD) in addition to normal IMAC, a reactive MAC population as well as increased levels of monocyte chemoattractant protein 1 (MCP-1) is found. The aim of this study was to investigate the influence of MCP-1 on the differentiation of MO into IMAC. MCS were generated from adenovirally transfected HT-29 cells overexpressing MCP-1, macrophage inflammatory protein 3 alpha (MIP-3alpha) or non-transfected controls and co-cultured with freshly elutriated blood MO. After 7 days of co-culture MCS were harvested, and expression of the surface antigens CD33 and CD14 as well as the intracellular MAC marker CD68 was determined by flow-cytometry or immunohistochemistry. MCP-1 and MIP-3alpha expression by HT-29 cells in the MCS was increased by transfection at the time of MCS formation. In contrast to MIP-3alpha, MCP-1 overexpression induced a massive migration of MO into the three-dimensional aggregates. Differentiation of IMAC was disturbed in MCP-1-transfected MCS compared to experiments with non-transfected control aggregates, or the MIP-3alpha-transfected MCS, as indicated by high CD14 expression of MO/IMAC cultured inside the MCP-1-transfected MCS, as shown by immunohistochemistry and FACS analysis. Neutralization of MCP-1 was followed by an almost complete absence of monocyte migration into the MCS. MCP-1 induced migration of MO into three-dimensional spheroids generated from HT-29 cells and inhibited intestinal-like differentiation of blood MO into IMAC. It may be speculated that MCP-1 could play a role in the disturbed IMAC differentiation in IBD mucosa.

Antigens, CD↗
PubMed2005

Glycoprotein (gp) 96 expression: induced during differentiation of intestinal macrophages but impaired in Crohn's disease.

BACKGROUND: The glycoprotein (gp) 96 links the adaptive with the innate immune system. It is a chaperone with a binding domain for peptides generated by proteasomal degradation. During cellular stress, peptide loaded gp96 can be released and presented to T cells by antigen presenting cells (APCs). METHODS: mRNAs from in vitro differentiated macrophages (iv mac) and normal intestinal macrophages (IMACs) were compared by subtractive hybridisation and Affymetrix GeneChip analysis. Differentiation induced expression of gp96 was investigated in the multicellular spheroid (MCS) model. In vivo gp96 protein expression was detected by double labelling immunohistochemistry of human colon and in the CD4+ CD62L+ T cell transfer mouse model. RESULTS: Five of 76 clones obtained by subtractive hybridisation revealed >99% sequence homology to gp96. Affymetrix GeneChip analysis confirmed induction of gp96 in IMACs. Gp96 mRNA was detected in IMACs from normal and intestinal bowel disease mucosa. Induction of gp96 protein was observed after seven days in the MCS model of IMAC differentiation. Immunohistochemistry confirmed the presence of gp96 protein in IMACs in normal mucosa as well as in mucosa from patients with ulcerative colitis and diverticulitis. In mucosa from Crohn's disease (CD) patients, gp96 protein was not detectable. In the CD4+ CD62L+ T cell transfer mouse model, gp96 was verifiable in non-activated IMACs. CONCLUSION: Gp96 is induced during differentiation of normal IMACs but is not detected in IMACs in CD mucosa. As gp96 has been described as having a role in tolerance induction, this may be relevant for loss of tolerance against luminal bacteria found in CD patients.

Animals↗
PubMed2004

Thioguanine-nucleotides do not predict efficacy of tioguanine in Crohn's disease.

BACKGROUND: 6-Thioguanine-nucleotides seem to be the active metabolites of thiopurine therapy, and their monitoring has been considered a useful tool for optimizing response in inflammatory bowel diseases. Tioguanine (thioguanine) therapy results in much higher levels of 6-thioguanine-nucleotide levels when compared with azathioprine or mercaptopurine. AIM: To elucidate the influence of 6-thioguanine-nucleotide and methylated 6-thioguanine-nucleotide levels under tioguanine on efficacy and toxicity in Crohn's disease. METHODS: 6-Thioguanine-nucleotide and methylated 6-tioguanine-nucleotide levels were measured regularly in 26 Crohn's disease patients treated with tioguanine. Nucleotide levels were related to efficacy and toxicity. RESULTS: 6-Thioguanine-nucleotide levels rose very high [median 1241 pmol/8 x 10(8) red blood cells (range 313-1853)]. Methylated 6-thioguanine-nucleotide levels were detected in all patients [491 pmol/8 x 10(8) red blood cells (154-1775)]. 6-Thioguanine-nucleotide and methylated 6-thioguanine-nucleotide concentrations correlated significantly (r = 0.7, P < 0.0001). Nucleotide levels from patients achieving remission (n = 14) did not differ significantly from non-remitters (n = 12) [6-thioguanine-nucleotide: 1077 (599-2160) vs. 1210 (534-4665); methylated 6-thioguanine-nucleotide: 510 (214-1222) vs. 421 (145-1284)]. One patient with intermediate thiopurine S-methyltransferase activity experienced bone marrow toxicity upon dose escalation parallel with excessively high thioguanine-nucleotide levels. CONCLUSIONS: 6-Thioguanine-nucleotide as well as methylated 6-thioguanine-nucleotide levels under tioguanine therapy were not related to efficacy. This suggests that monitoring of 6-thioguanine-nucleotide levels is not a useful tool to predict response to thiopurines.

Adult↗
PubMed2004

Oral capecitabine vs intravenous 5-fluorouracil and leucovorin: integrated efficacy data and novel analyses from two large, randomised, phase III trials.

This study evaluates the efficacy of capecitabine using data from a large, well-characterised population of patients with metastatic colorectal cancer (mCRC) treated in two identically designed phase III studies. A total of 1207 patients with previously untreated mCRC were randomised to either oral capecitabine (1250 mg m(-2) twice daily, days 1-14 every 21 days; n=603) or intravenous (i.v.) bolus 5-fluorouracil/leucovorin (5-FU/LV; Mayo Clinic regimen; n=604). Capecitabine demonstrated a statistically significant superior response rate compared with 5-FU/LV (26 vs 17%; P<0.0002). Subgroup analysis demonstrated that capecitabine consistently resulted in superior response rates (P<0.05), even in patient subgroups with poor prognostic indicators. The median time to response and duration of response were similar and time to progression (TTP) was equivalent in the two arms (hazard ratio (HR) 0.997, 95% confidence interval (CI) 0.885-1.123, P=0.95; median 4.6 vs 4.7 months with capecitabine and 5-FU/LV, respectively). Multivariate Cox regression analysis identified younger age, liver metastases, multiple metastases and poor Karnofsky Performance Status as independent prognostic indicators for poor TTP. Overall survival was equivalent in the two arms (HR 0.95, 95% CI 0.84-1.06, P=0.48; median 12.9 vs 12.8 months, respectively). Capecitabine results in superior response rate, equivalent TTP and overall survival, an improved safety profile and improved convenience compared with i.v. 5-FU/LV as first-line treatment for MCRC. For patients in whom fluoropyrimidine monotherapy is indicated, capecitabine should be strongly considered. Following encouraging results from phase I and II trials, randomised trials are evaluating capecitabine in combination with irinotecan, oxaliplatin and radiotherapy. Capecitabine is a suitable replacement for i.v. 5-FU as the backbone of colorectal cancer therapy.

Administration, Oral↗
PubMed2003

6-thioguanine--efficacy and safety in chronic active Crohn's disease.

BACKGROUND: : Azathioprine and mercaptopurine are commonly used in chronic active Crohn's disease. They share the disadvantage of a delayed onset of action and potentially serious side-effects, and are metabolized to thioguanine nucleotides which are thought to be the active metabolites. The direct use of 6-thioguanine may offer a more rapid and safer alternative. We conducted an open prospective study to investigate the efficacy and safety of 6-thioguanine in chronic active Crohn's disease. METHODS: : Thirty-seven patients with chronic active Crohn's disease and a Crohn's disease activity index of > 150 were enrolled in this study. Inclusion criteria were steroid dependence (n = 19), steroid refractoriness (n = 9) and/or intolerance (n = 16) or refractoriness (n = 6) to azathioprine. Patients were treated with 40 mg/day of 6-thioguanine for 24 weeks; a dose escalation to 80 mg was allowed at week 12. Remission was defined as a Crohn's disease activity index of < 150 associated with a decrease of > 70 points; response was defined as a decrease of > 70 points in the Crohn's disease activity index. RESULTS: : In the intention-to-treat analysis, 13 of 37 patients achieved remission (35%). Twelve of these 13 patients achieved remission after 4 weeks. Fifty-seven per cent of patients (21/37) achieved a response. The mean Crohn's disease activity index decreased from 284 +/- 74 to 153 +/- 101. 6-Thioguanine was more effective in azathioprine-intolerant than in azathioprine-refractory patients. Twelve of 16 patients intolerant to azathioprine tolerated 6-thioguanine. Adverse events included phototoxicity, pancreatitis, headache, nausea, alopecia, arthralgia, minor infections and reversible elevation of transaminases. Six patients required discontinuation of medication, two because of leucopenia. CONCLUSIONS: : In this patient group with chronic active Crohn's disease, 6-thioguanine appeared to be effective with acceptable short-term toxicity, but long-term controlled trials are clearly needed to further define its role.

Adult↗
PubMed1998

The accuracy of abdominal ultrasound in the assessment of bowel disorders.

BACKGROUND: Little is known about the sensitivity, specificity, and predictive values of transabdominal ultrasonographic (US) findings in a teaching hospital setting. METHODS: We carried out a prospective study including 227 patients with symptoms suggestive of inflammatory bowel disorder. The Picker 9200 CS equipment (5-mHz curved-array probe) was used to obtain bowel images. Gastrointestinal endoscopy, enteroclysis, bowel enema, computed tomography scan, or bowel surgery was used as reference. RESULTS: Of 227 patients, 168 had pathologic findings of the bowel as final diagnosis. The overall sensitivity of US was 76%, whereas the positive predictive value was 98%. Overall specificity was 95%. The negative predictive value for bowel disorders was only 58%, since US missed pathologic findings in 48 patients. Subgroup analysis showed a sensitivity of 84% for Crohn's disease, 66% for ulcerative colitis, 46% for bowel tumors, and 60% for diverticulitis. Topographic comparisons showed that US detected inflammatory bowel-wall alterations preferentially in the terminal ileum and colon, whereas abnormalities in the duodenum, jejunum, and rectum were frequently missed (sensitivity, 10%-20%). CONCLUSIONS: Positive US findings are useful for the diagnosis of bowel processes. US is highly predictive albeit not disease-specific. Negative US examinations, however, do not exclude pathologic bowel processes. A topographic location of pathologic US findings is mostly confined to the colon.

Adult↗
PubMed1989

Relapsing pancreatitis as initial manifestation of cystic fibrosis in a young man without pulmonary disease.

In young adults with acute pancreatitis a wide etiologic spectrum has to be considered. Among the possible causes, cystic fibrosis is rare. Besides the typical clinical triad of pancreatic exocrine insufficiency, chronic obstructive pulmonary disease, and elevated sweat chloride levels, there is a wide spectrum of variants of the cystic fibrosis syndrome. Especially mild manifestations of the disease may, therefore, escape proper identification. Here we describe a young man who presented initially with recurrent acute pancreatitis without pulmonary disease and without a family history of cystic fibrosis, in whom the diagnosis of cystic fibrosis was established by slightly elevated sweat chloride levels and obstructive azoospermia. Five years after the first attack of pancreatitis the patient developed pancreatic exocrine insufficiency.

Adult↗
PubMed1988

Clinical significance of abnormalities of the gastrointestinal tract detected by abdominal ultrasound.

In order to define the clinical significance and the need for further clinical work-up in patients where abnormalities of the stomach or bowel are found by ultrasound, we performed a prospective study on 100 patients with such findings. Of all patients, 35% were found to have a malignant tumor, 73% had a diagnosis as made by reference methods which was probably (18%) or definitively (55%) related to the US finding. Eighteen percent had definitive false positive findings, in 9% no final diagnosis was obtained. Thus, a positive predictive value of 80% was calculated for the US finding of a mass or a target sign related to bowel or stomach in US. The positive predictive value was lowest for target signs related to the bowel (75%) and highest for bowel conglomerates (100%). Patients with target signs of the stomach, bowel conglomerates, or masses were more likely to have malignant disorders (72%) than those with target signs related to the bowel (16%). We conclude from this study that the ultrasound finding of a target sign or a mass related to stomach or bowel has a high clinical relevance and should in any case worked up by appropriate investigations when clinical consequences are possible.

Digestive System↗
PubMed1985

Zinc and vitamin A deficiency in patients with Crohn's disease is correlated with activity but not with localization or extent of the disease.

A study of serum zinc and plasma vitamin A concentrations in 54 patients with Crohn's disease was performed. Compared with controls the patients had significantly lowered zinc and vitamin A concentrations. There was a marked correlation between zinc and vitamin A and the activity of the disease, as measured by the Crohn's disease activity index, and a weaker correlation with serum proteins considered to be indicators of disease activity. No correlation was found to vitamin B12 absorption, to the localization of the disease, or to previous ileal resection. The results suggest that zinc and vitamin A deficiency occurs in patients with active Crohn's disease and is not primarily caused by absorption abnormalities. Substitution might be helpful or even necessary in patients with highly active disease.

Adult↗
PubMed1984

A bioluminescence assay for total 3 alpha-hydroxy bile acids in serum using immobilized enzymes.

A bioluminescence assay for bile acids was developed using a co-immobilized 3 alpha-hydroxysteroid dehydrogenase, diaphorase, and bacterial luciferase. The assay was specific for bile acids containing a free 3 alpha-hydroxyl group, as well as androsterone. Light output was linear over a bile acid concentration range of 1-20 000 pmol. Intra-assay precision was 6.2-8.2% and the recovery of added standards was 92-110%. Comparison of results using the bioluminescence assay with those using gas liquid chromatography revealed an excellent correlation (r = 0.99, n = 31). Since the bioluminescence assay is rapid, sensitive, specific, and uses inexpensive reagents, it appears to be an ideal method for the measurement of total bile acids in serum.

3-Hydroxysteroid Dehydrogenases↗
PubMed1983

Changes of the pattern of biliary bile acids during isolated rat liver perfusion.

In spite of the extensive use of isolated perfused liver systems for bile acid related studies, the composition of biliary bile acids during liver perfusion is not well known. Using recently developed bioluminescence assays for 3 alpha-OH-, 7 alpha-OH-, and 12 alpha-OH- bile acids we studied the hydroxylation pattern of bile acids in bile during 90 minutes perfusion of isolated rat liver without added bile acid load. At the beginning 7 alpha-hydroxylated bile acids comprised more than 50% of total bile acids from male livers and more than 90% from female livers, this percentage declined rapidly during the first 40-50 minutes of perfusion to values between 10 and 20%. 12 alpha-hydroxylated bile acids comprised between 15 and 30% of the total at beginning of the perfusion and decreased to about 10% after 40 minutes. Sex differences as well as the influence of the duration of perfusion should be considered when the isolated perfused rat liver is used for bile acid related studies.

Animals↗