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Chris J J Mulder

Publications and source records attributed to Chris J J Mulder.

At least 19 recordsLinked to original sources
PubMed2006

Diet, lifestyle and risk of K-ras mutation-positive and -negative colorectal adenomas.

K-ras mutation-positive (K-ras+) and -negative (K-ras-) colorectal adenomas may differ clinically and pathologically. As environmental compounds may cause mutations in the growth-related K-ras oncogene or affect clonal selection depending on mutational status, we evaluated whether the aetiology of K-ras+ and K-ras- adenomas differs. K-ras mutations in codons 12 and 13 were assessed in colorectal adenoma tissue (K-ras+: n = 81, K-ras-: n = 453). Dietary and lifestyle data were collected through questionnaires that were also administered to 709 polyp-free controls. Multiple logistic regression analyses showed that intake of vitamin B2 and monounsaturated fat were differently associated with risk of K-ras+ and K-ras- adenomas; vitamin B2 was inversely associated with K-ras- (highest vs. lowest tertile: odds ratio (OR) = 0.70, 95% confidence interval (CI) = 0.50-0.97, p trend = 0.020), but not with K-ras+ adenomas, and a positive association with monounsaturated fat was confined to K-ras- adenomas (OR = 1.57, 95% CI = 1.06-2.34, p trend = 0.029). Besides, potential, not statistically significant, differences in risk arose because red meat was distinctly positively associated with K-ras+ adenomas (OR = 1.70, 95% CI = 0.94-3.09, p trend = 0.061); total dietary and polyunsaturated fat tended to be inversely associated with risk of K-ras+ but not of K-ras- adenomas; inverse associations with dairy products, calcium, protein and tea were confined to K-ras- adenomas, and smoking was more markedly positively associated with K-ras- adenomas. No differences in risk of K-ras+ and K-ras- adenomas could be detected for other factors. In conclusion, dietary and lifestyle factors may influence risk of K-ras+ and K-ras- adenomas differently. However, epidemiological literature on diet, lifestyle and colorectal K-ras mutations is inconsistent.

Adenoma↗
PubMed2006

Atrophy and defects detection of the external anal sphincter: comparison between three-dimensional anal endosonography and endoanal magnetic resonance imaging.

PURPOSE: Using endoanal magnetic resonance imaging, atrophy of the external anal sphincter can be established. This aspect has not been thoroughly investigated using three-dimensional anal endosonography. The purpose of this study was to compare prospectively three-dimensional anal endosonography to magnetic resonance imaging in the detection of atrophy and defects of the external anal sphincter in patients with fecal incontinence. In addition, we compared both techniques for anal sphincter thickness and length measurements. MATERIALS AND METHODS: Patients with fecal incontinence underwent three-dimensional anal endosonography and magnetic resonance imaging. Images of both endoluminal techniques were evaluated for atrophy and defects of the external anal sphincter. External anal sphincter atrophy scoring with three-dimensional anal endosonography depended on the distinction of the external anal sphincter and its reflectivity. External anal sphincter atrophy scoring with magnetic resonance imaging depended on the amount of muscle and the presence of fat replacement. Atrophy score was defined as none, moderate, and severe. A defect was defined at anal endosonography by a hypoechogenic zone and at magnetic resonance imaging as a discontinuity of the sphincteric ring and/or scar tissue. Differences between three-dimensional anal endosonography and magnetic resonance imaging for the detection of external anal sphincter atrophy and defects were calculated. In addition, we compared external anal sphincter thickness and length measurements in three-dimensional anal endosonography and magnetic resonance imaging. RESULTS: Eighteen patients were included (median age, 58 years; range, 27-80; 15 women). Three-dimensional anal endosonography and magnetic resonance imaging did not significantly differ for the detection of external anal sphincter atrophy (P = 0.25) and defects (P = 0.38). Three-dimensional anal endosonography demonstrated atrophy in 16 patients, magnetic resonance imaging detected atrophy in 13 patients. Three-dimensional anal endosonography agreed with magnetic resonance imaging in 15 of 18 patients for the detection of external anal sphincter atrophy. Using the grading system, 8 of the 18 patients scored the same grade. Three-dimensional anal endosonography detected seven external anal sphincter defects and magnetic resonance imaging detected ten. Three-dimensional anal endosonography and magnetic resonance imaging agreed on the detection of external anal sphincter defects in 13 of 18 patients. Comparison between three-dimensional anal endosonography and magnetic resonance imaging for sphincter thickness and length measurements showed no statistically significant concordance and had no correlation with external anal sphincter atrophy. CONCLUSION: This is the first study that shows that three-dimensional anal endosonography can be used for detecting external anal sphincter atrophy. Both endoanal techniques are comparable in detecting atrophy and defects of the external anal sphincter, although there is a substantial difference in grading of external anal sphincter atrophy. Correlation between three-dimensional anal endosonography and magnetic resonance imaging for thickness and length measurements is poor. Inconsistency between the two methods needs to be evaluated further.

Adult↗
PubMed2006

Disappearance of anti-Saccharomyces cerevisiae antibodies in coeliac disease during a gluten-free diet.

BACKGROUND: Anti-Saccharomyces cerevisiae antibodies (ASCAs) are known to be positive in about 65% of Crohn's disease patients, in up to 43% of coeliac disease patients and in 0-5% of healthy controls. Coeliac disease might be an in-vivo model for unravelling the role of mucosal integrity in the formation of ASCAs since mucosal abnormalities normalize during a gluten-free diet (GFD). AIMS: Firstly, to evaluate, retrospectively, the frequency of ASCA positivity in coeliac patients both at diagnosis and during follow-up on a GFD. Secondly, to study the correlation between ASCA positivity and mucosal damage. METHODS: One hundred and eleven patients with histologically proven coeliac disease, positive endomysium antibodies on diagnosis and normalization of trans-glutaminase antibodies (t-TGAs) after successful adherence to a GFD were included. ASCAs, IgA and IgG were tested by enzyme-linked immunosorbent assays both at diagnosis and after the GFD. RESULTS: Eighty-three children and 28 adults were included in this study. The mean age at diagnosis was 4.6 years for children and 48 years for adults. At diagnosis 15/83 (18%) of children were ASCA positive (either IgG or IgA), compared to 17/28 (61%) of adults. After successful adherence to a GFD and normalization of t-TGAs only one child remained ASCA positive (1%) compared to eight adults (29%). Two out of 28 (7%) adults remained positive for both IgA and IgG ASCAs. CONCLUSION: In the majority of patients ASCAs disappeared during a GFD. In children this disappearance of ASCA positivity was more pronounced. This can be explained by the well-known fact that gut permeability normalizes much better in children than in adults. Also, the adults had higher levels of ASCAs at diagnosis. This was probably because they had been exposed to gluten for longer and therefore had more long-lasting damage.

Adolescent↗
PubMed2006

A prospective study comparing video capsule endoscopy with double-balloon enteroscopy in patients with obscure gastrointestinal bleeding.

OBJECTIVE: Obscure gastrointestinal bleeding from jejunal and ileal lesions remains undiagnosed using traditional imaging techniques (radiologic, endoscopic). This prospective study compares the diagnostic detection rate of small-bowel lesions using wireless video capsule endoscopy (VCE) with the detection rate using double-balloon enteroscopy (DBE) in patients with obscure gastrointestinal bleeding (OGIB). Tolerance, adverse events, endoscopic interventions, and prognosis were described as secondary aims. METHODS: Thirty-five consecutive patients with obscure gastrointestinal bleeding were evaluated (22 males and 13 females; mean age 63.2 yr; range, 19-86 yr). The detection rates of the Given M2A wireless VCE and DBE were compared. RESULTS: Small-bowel abnormalities were detected using VCE in 28 (80%) of the 35 patients with OGIB, compared with 21 (60%) of the 35 patients using DBE (p = 0.01). Both examinations were well tolerated, but VCE was more acceptable to patients. No major adverse event occurred after either examination. Biopsies (n = 27), argon plasma coagulation (n = 19), tattoo injection (n = 8), and polypectomy (n = 2) were feasible with DBE when indicated in 27 of the 35 patients (77%). During a median (range) follow-up period of 5 (2-12) months, 26 (74%) patients remained clinically stable and did not require blood transfusions after DBE procedures. Eighteen (51%) of those who remained clinically stable had received APC therapy. CONCLUSIONS: High detection rates of the causes of OGIB are feasible with VCE and DBE. Although the detection rate of VCE was superior, our results indicate that the procedures are complementary; an initial diagnostic imaging employing VCE might be followed by therapeutic and interventional DBE.

Adult↗
PubMed2005

Myosin IXB variant increases the risk of celiac disease and points toward a primary intestinal barrier defect.

Celiac disease is probably the best-understood immune-related disorder. The disease presents in the small intestine and results from the interplay between multiple genes and gluten, the triggering environmental factor. Although HLA class II genes explain 40% of the heritable risk, non-HLA genes accounting for most of the familial clustering have not yet been identified. Here we report significant and replicable association (P = 2.1 x 10(-6)) to a common variant located in intron 28 of the gene myosin IXB (MYO9B), which encodes an unconventional myosin molecule that has a role in actin remodeling of epithelial enterocytes. Individuals homozygous with respect to the at-risk allele have a 2.3-times higher risk of celiac disease (P = 1.55 x 10(-5)). This result is suggestive of a primary impairment of the intestinal barrier in the etiology of celiac disease, which may explain why immunogenic gluten peptides are able to pass through the epithelial barrier.

Amino Acid Sequence↗
PubMed2005

Case-finding in coeliac disease should be intensified.

Large-scale screening studies on CD have been published and suggest a prevalence of CD in USA, Europe, Middle-East and Australia of about 1:100. The costs of finding coeliacs hasn't been discussed in these studies. Coeliac disease can be classified to be an important health problem. It might be relevant to have a low threshold for biopsies when screening for coeliac disease. Screening asymptomatics may be harmful for individuals. A lifelong gluten-free diet is not easy to maintain and quality of life may deteriorate. In countries familiar with coeliac disease, the classic pattern of severe malabsorption and cachexia, as described in textbooks, has become rare. CD is not borne in minds of doctors diagnosing dyspepsia and/or irritable bowel disease, or associated auto-immune diseases. The consequence is a delay in diagnosis, with secondary problems as long term auto-immune stimulation, osteoporosis and secondary malignancies. Enteropathy associated T-cell lymphomas are well known, but considering coeliac disease in T-cell lymphomas presenting outside the GE-tract is uncommon. Nation-wide screening programmes have not started, which are common for phenylketonury and other metabolic defects. It is debatable whether coeliacs found by screening adhere to a gluten-free diet similar to symptomatic coeliacs. Whether a gluten-free diet is of benefit to this subgroup is controversial.

Celiac Disease↗
PubMed2005

Refractory coeliac disease.

A small proportion of coeliac disease (CD) patients fail to improve after a gluten-free diet (GFD) and may be considered as atypical regarding their outcome (refractory coeliac disease). The aim of this study is to diagnose and manage patients with CD who fail to improve after a GFD. Refractory coeliac disease (RCD) is a malabsorption syndrome defined by persisting villous atrophy with, usually, an increase of intraepithelial lymphocytes (IELs) in the small bowel in spite of a strict GFD and comprises a heterogenous group of diseases. Some of these diseases have to be excluded and can be treated by specific therapies like antibiotics in tropical sprue and giardiasis and immune globulin substitution in common variable immunodeficiency, while other malabsorption syndromes are less well defined and may require immunosuppressive therapy. Standardized treatment, however, has not been evaluated in such patients so far. In a subgroup of patients with RCD, an abnormal intraepithelial lymphocyte (IEL) population may be observed with the lack of surface expression of usual T-cell markers (CD3-CD8 and/or the T-cell receptor (TCR)) on IELs associated with T-cell clonality pattern suggest the presence of an early enteropathy-associated T-cell lymphoma (EATL) in a subgroup of patients with RCD. This hypothesis has been supported by studies, which revealed progression into overt intestinal T-cell lymphomas in a subgroup of RCD. Steroid treatment has been reported effective even in patients with underlying early EATL. However, long-term results are unsatisfactory in most of these patients with RCD and parenteral nutrition has to be applied in some of these cases. First results with more aggressive chemotherapies and use of cytokines are under way. Due to the difficulty of diagnostic and therapeutic regimens patients should be referred to tertiary centres for coeliac disease.

Celiac Disease↗
PubMed2005

6-Thioguanine for Crohn's disease during pregnancy: thiopurine metabolite measurements in both mother and child.

6-Thioguanine is used as an escape thiopurine for treating inflammatory bowel disease patients intolerant or refractory to azathioprine, 6-mercaptopurine or methotrexate. Case reports show conflicting data on the use of 6-thioguanine throughout pregnancy. The administration of the standard thiopurines is believed to be relatively safe. We describe two patients with Crohn's disease treated with low-dose 6-thioguanine during all trimesters of their pregnancies. The pregnancies resulted in two healthy infants: without congenital abnormalities, laboratory signs of myelosuppression or hepatocellular injury. Thiopurine metabolites were measured in mother and infant. Significantly lower levels of 6-thioguaninenucleotides were found in the erythrocytes of the infant compared to the mother (ratio 1:12). Further studies are needed to determine the clinical importance of thiopurine metabolite measurements during pregnancy in mother and child.

Adult↗
PubMed2005

Antiendomysial and antihuman recombinant tissue transglutaminase antibodies in the diagnosis of coeliac disease: a biopsy-proven European multicentre study.

OBJECTIVE: To investigate the value of serum antitissue transglutaminase IgA antibodies (IgA-TTG) and IgA antiendomysial antibodies (IgA-EMA) in the diagnosis of coeliac disease in cohorts from different geographical areas in Europe. The setting allowed a further comparison between the antibody results and the conventional small-intestinal histology. METHODS: A total of 144 cases with coeliac disease [median age 19.5 years (range 0.9-81.4)], and 127 disease controls [median age 29.2 years (range 0.5-79.0)], were recruited, on the basis of biopsy, from 13 centres in nine countries. All biopsy specimens were re-evaluated and classified blindly a second time by two investigators. IgA-TTG were determined by ELISA with human recombinant antigen and IgA-EMA by an immunofluorescence test with human umbilical cord as antigen. RESULTS: The quality of the biopsy specimens was not acceptable in 29 (10.7%) of 271 cases and a reliable judgement could not be made, mainly due to poor orientation of the samples. The primary clinical diagnosis and the second classification of the biopsy specimens were divergent in nine cases, and one patient was initially enrolled in the wrong group. Thus, 126 coeliac patients and 106 controls, verified by biopsy, remained for final analysis. The sensitivity of IgA-TTG was 94% and IgA-EMA 89%, the specificity was 99% and 98%, respectively. CONCLUSIONS: Serum IgA-TTG measurement is effective and at least as good as IgA-EMA in the identification of coeliac disease. Due to a high percentage of poor histological specimens, the diagnosis of coeliac disease should not depend only on biopsy, but in addition the clinical picture and serology should be considered.

Adolescent↗
PubMed2005

Promising treatment of autoimmune hepatitis with 6-thioguanine after adverse events on azathioprine.

The use of corticosteroids in autoimmune hepatitis is an established therapy. To avoid the possible serious side effects of corticosteroids, immunosuppression with azathioprine is often warranted. Azathioprine, a purine analogue, is frequently used to taper or replace corticosteroids. However, approximately 10% of the patients are intolerant to azathioprine. Alternative therapies using mycophenolate, tacrolimus, budesonide, cyclosporine and 6-mercaptopurine have been studied, with variable results. The use of 6-thioguanine, an agent more directly leading to the down-stream active metabolites of azathioprine (6-thioguanine nucleotides) in inflammatory bowel disease patients intolerant to azathioprine or 6-mercaptopurine showed conflicting results. We report three patients with autoimmune hepatitis who could not tolerate azathioprine but tolerated 6-thioguanine 0.3 milligram per kilogram daily well. All three patients improved clinically. Therapeutic drug monitoring was performed. The prospective evaluation of 6-thioguanine as a possible immunosuppressive drug in autoimmune hepatitis patients is warranted.

Aged↗
PubMed2005

A candidate gene approach of immune mediators effecting the susceptibility to and severity of upper gastrointestinal tract diseases in relation to Helicobacter pylori and Epstein-Barr virus infections.

This review focuses on immunogenetic aspects of diseases of the upper gastrointestinal tract in which infectious agents may play a role in the aetiopathogenesis, such as Helicobacter pylori, Epstein-Barr virus (EBV) and HIV. Gastric adenocarcinoma is a common cancer all around the world, with declining incidences in Europe and high incidences in Asia and central and south America. Together with gastric atrophy and peptic ulcer disease, gastric adenocarcinoma belongs to the commonest upper gastrointestinal tract diseases. These diseases are multifactorial and factors such as smoking and dietary habits contribute to the pathogenesis. More recently, scientists have turned their eyes on the host. Functional polymorphisms in the genes regulating the host immune system may contribute to the susceptibility to and progression of disease. In multifactorial and polygenetic diseases, candidate gene studies of single nucleotide polymorphisms (SNPs) detect small to moderate relative risks. Unfortunately, only a few functional SNPs have been identified. The candidate gene approach can be seen as a useful first step in exploring causal pathways between genetic determinants and complex diseases such as those mentioned above. To date, little is known about the immunogenetics of upper gastrointestinal tract diseases. We review the literature on H. pylori, EBV and gene polymorphisms that affect key immune mediators influencing the pathogenesis of the inflammatory response, such as the genes that code for the IL-1 family, TNF-alpha, lymphotoxin alpha, and IL-10. IL-1, IL-10, lymphotoxin alpha and TNF-alpha polymorphisms increase the risk of upper gastrointestinal pathogenesis in H. pylori-infected patients, whereas IL-1 and TNF-alpha polymorphisms confer risk in EBV-infected patients.

Cytokines↗
PubMed2005

Does treatment of coeliac disease require full mucosal recovery?

Glutenfree diet is recommended for all coeliacs. There are almost no data on effective means of monitoring coeliacs. Some consider a decrease in antibody titer as an indication of dietary adherence. A recent American pediatric guideline suggests that additional biopsies are not recommended. The UEGW group about adult coeliacs advises a second biopsy after one year. The required normalisation has not been defined. Serology does not indicate complete mucosal recovery and cannot substitute for follow-up biopsy. Biopsy findings may not always be as conclusive as is imaging in explaining persistent complaints in coeliacs. Treating almost daily refractory coeliacs on their way to EATL, we suggest mucosal recovery is the only protection against such complications, especially in coeliacs diagnosed above the age of 50, so-called old-age coeliacs. A body of published data is mandatory to see if full mucosal recovery is required and is achievable. In countries where gluten-free products are not easily available as in Eastern Europe or the Middle East, this might be extremely difficult for the coeliacs, their doctors and dietitians.

Biopsy↗
PubMed2005

Endoscopic tattoo of the colon might be standardized to locate tumors intraoperatively.

BACKGROUND: Small colonic lesions which are identified during endoscopy are usually difficult to locate intra-operatively. Endoscopic tattoo of the colon seems the most efficient method, however it does fail in some cases to identify the lesion peroperatively. We studied this method to evaluate its efficacy. METHODS: Nineteen patients were tattooed during colonoscopy with "India ink" (drawing ink Rotring ). These patients had lesions in which difficulties were anticipated when retracing them again during colorectal surgery. Seventeen patients underwent colonic surgery. One patient underwent laparoscopic polypectomy and the other TEM (Transanal Endoscopic Microsurgery). RESULTS: The visibility of the "India ink" peroperatively and afterwards during histological examination were evaluated. The tattoos were visible in 68.4 % patients intraoperatively. Histopathological macroscopic examination of the specimens showed ink in 73.6 % patients. In 31.5 % patients the tattoo could not be recognised peroperatively. CONCLUSIONS: Endoscopy assisted tattooing of the colon has been reported to be a safe method to landmark lesions in the colon. In the majority of our patients the tattoo was obvious during surgery. Endoscopic tattoo seems an efficient technique in identifying small colonic lesions intraoperatively.

Colonic Neoplasms↗
PubMed2004

The interferon gamma gene in celiac disease: augmented expression correlates with tissue damage but no evidence for genetic susceptibility.

Celiac disease (CD) is a complex genetic disorder characterized by gluten intolerance. The Th1 immune response, with a key position for interferon gamma (IFN-gamma), is an important determinant of intestinal remodeling in CD. We aimed at further ascertaining the role of IFN-gamma, either as a genetic factor in the etiology, or as a facilitator of disease initiation/progression. Duodenal biopsies were sampled across distinct histopathological stages of the disease, including refractory CD (RCD), and used to determine IFN-gamma gene (IFNG) expression by real-time RT-PCR. INFG expression correlated with the extent of tissue restructuring, reaching a 240-fold higher expression in total villous atrophy compared to healthy tissue. CD and RCD patients with similar lesions had comparable expression levels. Interestingly, patients in complete remission still had 7.6-fold residual over-expression. An INFG marker was tested in three cohorts of Dutch patients for both genetic linkage and association. Linkage analysis yielded no significant scores for IFNG or its flanking markers. In addition, IFNG allele frequencies were not differently distributed between cases and controls. Likewise, all alleles were randomly transmitted to affected children in parents-case trios. There is no evidence for IFNG as a predisposing gene in CD, despite its enhanced expression in patients in complete remission.

Adult↗
PubMed2004

CTLA4 +49 A/G and CT60 polymorphisms in Dutch coeliac disease patients.

Coeliac disease is an autoimmune disorder, characterised by villous atrophy of the small intestine, which results from a T-cell-mediated response to gluten-derived peptides. The cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is involved in the regulation of T-cell activation and the CTLA4 +49 A/G polymorphism in exon 1 has been implicated in several autoimmune disorders, including coeliac disease. However, this polymorphism was recently excluded as being the causal variant in Graves' disease, autoimmune hypothyroidism and type I diabetes mellitus. This causal variant was mapped to the 3' region of CTLA4, with the CT60 polymorphism showing the strongest association. The aim of this study was to determine the role of the CTLA4 gene in coeliac disease in the Dutch population. The +49 A/G and CT60 polymorphisms were genotyped in a case-control cohort of 215 patients and controls. The frequency of the +49 G-allele was increased in cases, although not significantly. However, the frequency of the CT60 G-allele was increased with borderline significance in coeliac disease patients (P = 0.048), although the genotype distributions did not show a significant difference between cases and controls. These results indicate the involvement of the CTLA4 gene in coeliac disease development. The haplotype carrying the CT60 G-allele was shown to be associated with lower mRNA levels of the soluble CTLA-4 isoform, providing a possible mechanism for the T-cell-mediated destruction of the small intestine.

Adult↗