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Biomedical subjects

H M van Dullemen

Publications and source records attributed to H M van Dullemen.

At least 19 recordsLinked to original sources
PubMed2006

CARD15 in inflammatory bowel disease and Crohn's disease phenotypes: an association study and pooled analysis.

BACKGROUND: Three major polymorphisms of the Caspase-Activation Recruitment Domain containing protein 15 gene have been described to be associated with Crohn's disease. Genotype-phenotype studies reported in literature provide conflicting data on disease localisation and behaviour. We investigated the relation of Caspase-Activation Recruitment Domain containing protein 15 with inflammatory bowel disease and Crohn's disease phenotypic characteristics in a large Dutch cohort and performed a pooled analysis on inflammatory bowel disease patients and Crohn's disease phenotypic characteristics reported in association studies. METHODS: We genotyped 781 cases and 315 controls for the R702W, G908R and 1007fsinsC variants and for six microsatellite markers in and close to Caspase-Activation Recruitment Domain containing protein 15. In the pooled analysis data of 7201 inflammatory bowel disease patients and 3720 controls from 20 studies were included. RESULTS: Association was found for Crohn's disease with R702W and 1007fsinsC, including several disease characteristics, and not for ulcerative colitis. In the pooled analysis all three common Caspase-Activation Recruitment Domain containing protein 15 variants showed strong association with Crohn's disease (p<0.00001; odds ratio varying from 3.0 for single heterozygotes to 14.7 for compound heterozygotes) and not with ulcerative colitis. Phenotype analysis showed association with small bowel involvement, stricturing and penetrating disease. CONCLUSION: Caspase-Activation Recruitment Domain containing protein 15 is associated with Crohn's disease and not with ulcerative colitis. All three common Crohn's disease-associated variants are associated with small bowel involvement, the G908R and 1007fsinsC alleles also being associated with a complicated disease course.

Adolescent↗
PubMed2006

[Treatment of servere ulcerative colitis].

10-15% of patients with ulcerative colitis experience a severe episode of colonic inflammation that does not respond to mesalazine and oral corticosteroids. These patients require hospitalisation and treatment with intravenous corticosteroids. However, 25% of these patients do not respond to treatment. In these cases, intravenous cyclosporin is effective. Infliximab, an antibody against tumour necrosis factor alpha, is also beneficial. With these new treatment options, the colectomy rate in the acute phase has declined to about 35%. Other new therapies are under investigation in phase 2 and 3 trials. Surgery remains an important treatment option. Patients, gastroenterologists and surgeons should be involved in the clinical decision-making process.

Adrenal Cortex Hormones↗
PubMed2006

Novel approaches in the outpatient care of patients with chronic inflammatory bowel disease.

Treatment strategies for Crohn's disease are targeted toward lifelong management. Optimization of outpatient care is mandatory, because of many clinics facing capacity issues, and, along with routine follow-up of patients with inflammatory bowel disease, is putting increasing pressure on outpatient clinics. Recent studies demonstrate clearly that alternative management strategies are feasible and effective with a high rate of patient satisfaction. It is recommended that future research evaluates the way in which medical care is provided and explores the long-term effects of novel management strategies in IBD. This approach can then be extrapolated to other chronic conditions.

Ambulatory Care↗
PubMed2005

[Small bowel transplantation as a treatment option for intestinal failure in children and adults].

Small bowel transplantation for intestinal failure is no longer an experimental procedure, but an accepted treatment for patients where total parenteral nutrition (TPN) therapy for intestinal failure is unsuccessful. Early referral for screening for small bowel transplantation should be considered in patients with permanent intestinal failure who have occlusion of more than 2 major veins, frequent line-related septic episodes, impairment of liver function or an unacceptable quality of life. With the increased experience in post-transplant patient care and newer forms of induction (thymoglobulin, IL-2 receptor antagonists) and maintenance (tacrolimus) therapies, the 1-year graft survival has increased to 65% for isolated and to 59% for liver/small bowel transplantation and is further improving. Rejection, bacterial, fungal and viral (Cytomegalovirus, Epstein-Barr-virus) infections, post-transplant lymphoproliferative disease and graft versus host disease are the most common complications after intestinal transplantation. Although most of the long-term survivors are TPN-independent and have a good quality of life, the risk of the procedure and long-term adverse effects ofimmunosuppressive medication limits small bowel, or liver/small bowel transplantation only to patients with severe complications of TPN therapy.

Adult↗
PubMed2005

Bacterial population analysis of human colon and terminal ileum biopsies with 16S rRNA-based fluorescent probes: commensal bacteria live in suspension and have no direct contact with epithelial cells.

BACKGROUND: The commensal intestinal microflora has important metabolic and perhaps also immune modulatory functions. Evidence has accumulated that the microflora plays a role in the pathogenesis of inflammatory bowel disease. Therefore, there is a growing interest in the intestinal microflora and its interaction with the host. Presumably, this interaction takes place at the mucus layer. In this study, we investigated the microflora that is present at the mucus layer and addressed the following questions. Does a specific mucus-adherent microflora exist? Is there direct contact between commensal bacteria and epithelial cells? METHODS: Snap-frozen biopsies were taken of 5 colon regions and of the terminal ileum in 9 subjects with a normal colon. Fecal samples were also collected. Bacteria were detected in cryosections with fluorescent in situ hybridization (FISH) with 16S ribosomal (r)RNA-targeted probes for all bacteria and specific probes for the major representatives of anaerobic microflora (bifidobacteria, Bacteroides, clostridia, atopobia) and aerobic microflora (Enterobacteriaceae, enterococci, streptococci, lactobacilli). RESULTS: With this sensitive technique, bacteria were only observed at the luminal side of the intestinal mucus layer. Very few microcolonies were present at the mucus layer, and the composition of the bacterial microflora present in the feces was similar to that at the mucus layer of the terminal ileum and colon regions. CONCLUSIONS: We did not observe direct contact between bacteria and epithelial cells. The equal distribution of bacterial species suggests that intestinal commensal bacteria live in suspension in the lumen and that there is no specific mucus-adherent microflora.

Adolescent↗
PubMed2004

Increased incidence of azathioprine-induced pancreatitis in Crohn's disease compared with other diseases.

BACKGROUND: Azathioprine is widely used in Crohn's disease. A major drawback is the occurrence of side-effects, especially acute pancreatitis. Acute pancreatitis is rarely seen when azathioprine is used for other diseases than Crohn's disease. AIM: To survey side-effects of azathioprine after liver or renal transplantation, for systemic lupus erythematosis, Wegener's granulomatosis, autoimmune hepatitis, rheumatoid arthritis, ulcerative colitis or Crohn's disease. METHODS: A computerized search using the term 'azathioprine' or 'imuran' was performed on the Hospital Information System of the university hospital Groningen, resulting in 1564 patients matching our criteria. RESULTS: Eleven of 224 patients with Crohn's disease experienced acute pancreatitis (4.9%) compared with two of 129 (1.5%) with autoimmune hepatitis, two of 388 (0.5%) after renal transplantation, one of 254 (0.4%) after liver transplantation. Acute pancreatitis was more prevalent in Crohn's disease compared with any other disease. Azathioprine-toxicity necessitating withdrawal occurred significantly (P < 0,05) more in rheumatoid arthritis (78 of 317), ulcerative colitis (20 of 94) and Crohn's disease (52 of 224) compared with systemic lupus erythematosis (five of 73), Wegener's granulomatosis (six of 85), autoimmune hepatitis (eight of 129), after liver transplantation (17 of 254) and after renal transplantation (22 of 388). CONCLUSIONS: Acute pancreatitis is strongly associated with Crohn's disease and rarely occurs with other underlying conditions. Overall azathioprine-induced toxicity and the necessity of withdrawal is more common in inflammatory bowel disease and rheumatoid arthritis compared with other diseases.

Acute Disease↗
PubMed2004

Influence of tumor characteristics on the accuracy of endoscopic ultrasonography in staging cancer of the esophagus and esophagogastric junction.

BACKGROUND AND STUDY AIMS: Endoscopic ultrasonography (EUS) is the most accurate method of assessing the locoregional extent of cancer of the esophagus and esophagogastric junction. The aim of this study was to evaluate the influence of tumor-related factors such as length and location on the accuracy of EUS in staging these tumors. PATIENTS AND METHODS: Between January 1997 and September 2002, 280 consecutive patients underwent preoperative EUS for staging cancer of the esophagus and esophagogastric junction. The influence of histopathology, the presence of Barrett's dysplasia or stenosis, and the location and length of the primary tumor on the accuracy of EUS for T, N, and M staging were studied. RESULTS: The overall accuracy rates of EUS for assessing the T, N, and M stages were 73 %, 80 %, and 78 %, respectively. The influence of the tumor's histopathology and the presence of Barrett's dysplasia or stenosis was minimal. The accuracy of EUS was greater in tumors 5 cm or less in size than in tumors larger than 5 cm (82 % vs. 52 % for the T stage, P < 0.05; 88 % vs. 59 % for the N stage, P < 0.05; and 92 % vs. 56 % for the M stage, P < 0.001). The low accuracy of T staging in larger tumors may be due to the exclusion of patients with local unresectability or distant metastases. EUS was also significantly better in esophageal tumors, particularly for identifying celiac trunk metastases (93 % vs. 63 %; P < 0.001). CONCLUSIONS: The accuracy of EUS for staging esophageal cancer is lower in tumors larger than 5 cm and in esophagogastric junction tumors than in tumors 5 cm in size or less and in esophageal tumors. These findings should be considered when treatment decisions are being taken.

Adenocarcinoma↗
PubMed2004

Oesophageal endoscopic ultrasound with fine needle aspiration improves and simplifies the staging of lung cancer.

BACKGROUND: Positron emission tomography (PET) is accurate for mediastinal staging of lung cancer but has a moderate positive predictive value, necessitating pathological verification. Endoscopic ultrasonography with fine needle aspiration (EUS-FNA) is a technique for tissue verification of mediastinal and upper retroperitoneal abnormalities. The use of EUS-FNA may decrease the number of surgical procedures and thereby staging costs. METHODS: EUS-FNA was used prospectively for the cytological assessment of mediastinal and/or upper retroperitoneal PET hot spots in patients with suspected lung cancer. Only if EUS-FNA was positive for malignancy was subsequent mediastinoscopy or exploratory thoracotomy cancelled. The cost effectiveness of EUS-FNA was determined. RESULTS: Of 488 consecutive patients with suspected lung cancer, 81 were enrolled with mediastinal and/or upper retroperitoneal PET hot spots. EUS-FNA was positive in 50 (62%) patients, negative in six, and inconclusive in 25. Of the 31 negative or inconclusive patients, 26 underwent surgical staging (resulting in 14 patients with and 12 without mediastinal malignancy), while five patients had mediastinal metastases during follow up. No EUS-FNA related morbidity or mortality was encountered. The accuracy of the decision to proceed to surgery (or not) on the basis of EUS-FNA was 77% (95% CI 68 to 86). EUS-FNA detected more mediastinal abnormalities than PET except for the upper mediastinal region. Addition of EUS-FNA to conventional lung cancer staging reduced staging costs by 40% per patient, mainly due to a decrease in surgical staging procedures. CONCLUSION: EUS-FNA can replace more than half of the surgical staging procedures in lung cancer patients with mediastinal and/or upper retroperitoneal PET hot spots, thereby saving 40% of staging costs.

Adult↗
PubMed2003

IBD and genetics: new developments.

BACKGROUND: Inflammatory bowel disease (IBD) is a complex disorder with an aetiology that is only partly understood. Apart from environmental factors, inheritance contributes to IBD. REVIEW: Family studies show an increased risk among family members of a patient with IBD, particularly among first-degree relatives. In twin studies, concordance for disease type and localization is observed. In genetically isolated groups there is a higher prevalence of IBD. For instance. Ashkenazi Jews carry the highest risk. Further evidence comes from animal species that spontaneously develop IBD. Unlike Mendelian inheritance, in complex genetic diseases like IBD, genes are expected to be low penetrant and therefore less prone to selection, which results in higher expected gene frequencies. NOD2/CARD15, the first gene associated with IBD, is a polymorphic gene involved in the innate immune system. The gene has over 60 variations. Three of these play a role in 27% of patients with CD, with a predilection for patients with ileal disease. CONCLUSION: Genetics plays an important role in unravelling the pathogenesis of IBD leading to possible new therapeutic approaches.

Carrier Proteins↗
PubMed2002

Effects of anti-tumour necrosis factor-alpha therapy on the quality of life in Crohn's disease.

BACKGROUND: Infusion of anti-tumour necrosis factor-alpha appears to be highly effective in patients with Crohn's disease. AIM: To assess the effect of infliximab on the quality of life in patients with active or fistulizing disease, as measured by the inflammatory bowel disease questionnaire, and to examine the impact on its four dimensions. METHODS: An observational study was conducted in 65 patients. An infusion of 5 mg/kg infliximab was given at week 0 in patients with active disease and at week 0, 2 and 6 in fistulizing disease. Changes from baseline in the total and dimensional inflammatory bowel disease questionnaire scores were calculated and compared between the patient groups. Potential predictors of change in the quality of life were identified. RESULTS: In the active disease group, at week 4, the mean total and dimensional inflammatory bowel disease questionnaire scores improved compared to baseline (P < 0.001). In the fistulizing group, at week 6, all scores changed from baseline (P < 0.05). Improvement in the total inflammatory bowel disease questionnaire score correlated well with the improvement of the Crohn's disease activity index. Systemic and social scores improved more than bowel and emotional scores. Inflammatory Crohn's disease and a young age at diagnosis were predictors for a better response to infliximab therapy. CONCLUSIONS: Infliximab therapy improves all dimensions of the quality of life in patients with Crohn's disease.

Adult↗
PubMed2002

Increased expression of inducible nitric oxide synthase in circulating monocytes from patients with active inflammatory bowel disease.

BACKGROUND: Inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) synthesis are increased in epithelial cells and in tissue macrophages of the inflamed mucosa from patients with inflammatory bowel disease (IBD). Since tissue macrophages are derived from circulating monocytes, we studied iNOS expression in circulating monocytes and related this expression to disease activity. In view of the possible role of NO in monocyte function, we also studied iNOS expression in relation to markers of monocyte activation. METHODS: The expression of iNOS in circulating monocytes from 15 patients with active IBD, 6 patients who went into remission and 18 healthy controls was quantified by flow cytometry and correlated with surface markers (CD63, CD11b, HLA-DR) for monocyte activation. In addition, iNOS expression in circulating monocytes was assessed by Western blotting, immunocytochemistry and measurement of the NO metabolites nitrite and nitrate in plasma. RESULTS: The expression of iNOS in circulating monocytes and the percentage of iNOS-positive monocytes were increased in patients with active IBD compared to healthy controls (fluorescence index: 1.3 (0.1-6.3) versus 0.8 (0.0-1.8); P < 0.05: percentage of iNOS positive monocytes: 37.3 (1.0-77.0)% versus 5.3 (0.0-43.3)%; P<0.01). The six patients who went into remission all had a marked reduction of iNOS expression. iNOS expression was confirmed by Western blotting and immunocytochemistry. Plasma nitrite and nitrate levels were elevated in three patients with active 1BD. The surface markers for monocyte activation, CD63 and CD11b, were not elevated. HLA-DR expression was decreased on circulating monocytes from patients with active ulcerative colitis. CONCLUSIONS: iNOS is increased in circulating monocytes from patients with active IBD and this increased expression correlates with disease activity. Considering the decreased HLA-DR expression and absence of monocyte activation markers, NO produced by iNOS may have a function in suppressing systemic monocyte activation.

Adult↗
PubMed1998

Expression of nitric oxide synthases and formation of nitrotyrosine and reactive oxygen species in inflammatory bowel disease.

Nitric oxide (NO) and reactive oxygen species (ROS) are important mediators in the pathogenesis of inflammatory bowel disease (IBD). NO in IBD can be either harmful or protective. NO can react with superoxide anions (O2.-), yielding the toxic oxidizing agent peroxynitrite (ONOO-). Peroxynitrite induces nitration of tyrosine residues (nitrotyrosine), leading to changes of protein structure and function. The aim of this study was to identify the cellular source of inducible nitric oxide synthase (iNOS) and to localize superoxide anion-producing cells in mucosal biopsies from patients with active IBD. Additional studies were performed to look at nitrotyrosine formation as a measure of peroxynitrite-mediated tissue damage. For this, antibodies against iNOS, endothelial NOS (eNOS), and nitrotyrosine were used. ROS-producing cells were detected cytochemically. Inflamed mucosa of patients with active IBD showed intense iNOS staining in the epithelial cells. iNOS could not be detected in non-inflamed mucosa of IBD patients and control subjects. eNOS was present in blood vessels, without any difference in the staining intensity between IBD patients and control subjects. ROS-producing cells were increased in the lamina propria of IBD patients; a fraction of these cells were CD15-positive. Nitrotyrosine formation was found on ROS-positive cells. These results show that iNOS is induced in epithelial cells from patients with active ulcerative colitis or Crohn's disease. Nitration of proteins was detected only on the ROS-producing cells at some distance from the iNOS-producing epithelial cells. These findings indicate that tissue damage during active inflammation in IBD patients is probably more related to ROS-producing cells than to NO. One may speculate that NO has a protective role when during active inflammation other mucosal defence systems are impaired.

Adult↗
PubMed1998

Treatment of therapy-resistant perineal metastatic Crohn's disease after proctectomy using anti-tumor necrosis factor chimeric monoclonal antibody, cA2: report of two cases.

PURPOSE: Two young females with well-documented Crohn's disease and nonhealing perineal wounds following proctectomy compatible with "metastatic Crohn's disease" are described. We hypothesized that metastatic Crohn's disease would be a tumor necrosis factor-dependent inflammatory reaction and have treated these two patients with the anti-tumor necrosis factor chimeric monoclonal antibody, cA2. MAIN FINDINGS: Administration of cA2 was followed by a rapid reduction of subjective and objective parameters of inflammation and caused a substantial reduction of the wound size. CONCLUSION: These preliminary data are consistent with a tumor necrosis factor-dependent inflammatory cause of Crohn's disease and its extraintestinal manifestations and provide support for targeting tumor necrosis factor in this condition.

Adult↗
PubMed1998

Reduction of circulating secretory phospholipase A2 levels by anti-tumor necrosis factor chimeric monoclonal antibody in patients with severe Crohn's disease. Relation between tumor necrosis factor and secretory phospholipase A2 in healthy humans and in active Crohn's disease.

BACKGROUND: Secretory phospholipase A2 group II (sPLA2-II) has pro-inflammatory effects. The importance of tumor necrosis factor (TNF) for induction of plasma sPLA2-II in humans was studied in two groups of subjects. SUBJECTS: Six healthy volunteers received a single intravenous injection of recombinant human TNF or isotonic saline at random. Ten patients with active Crohn's disease received a single intravenous infusion of an anti-TNF chimeric monoclonal antibody, cA2. RESULTS: TNF infusion in healthy volunteers resulted in an increase of sPLA2-II at 3 h, with a maximal plasma level at 6 h (20.8+/-8.9 ng/ml; P < 0.05). In Crohn's disease base-line sPLA2-II levels were 33.9+/-13.4 ng/ml 24 h after infusion of cA2, 11.0+/-2.9 ng/ml (P < 0.005). Further decrease occurred in all except two patients at 2 weeks. The decrease in plasma sPLA2-II preceded all clinical signs of remission. CONCLUSION: TNF infusion in healthy humans can induce a rapid increase of circulating sPLA2-II, and selective blocking of TNF-alpha with cA2 results in a rapid decrease in sPLA2-II in peripheral blood. These data confirm that TNF has an important role in regulating the release of sPLA2-II in systemic and local inflammatory reactions.

Adult↗