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C J Mulder

Publications and source records attributed to C J Mulder.

At least 19 recordsLinked to original sources
PubMed2006

Double-balloon enteroscopy: indications, diagnostic yield, and complications in a series of 275 patients with suspected small-bowel disease.

BACKGROUND AND STUDY AIMS: Until recently, only the proximal small bowel was accessible for diagnostic and therapeutic endoscopy. This paper describes experience in the first 275 patients examined and treated with the new method of double-balloon enteroscopy (DBE), which is expected to make full-length enteroscopy possible. PATIENTS AND METHODS: Between November 2003 and May 2005, double-balloon enteroscopy was conducted in 275 consecutive patients presenting at two tertiary referral hospitals. The characteristics of the patients, indications for the procedures, procedural parameters, and diagnostic yield are described here. All conventional treatment options were available. The tolerability of the procedure was assessed in a small subset of the patients. After the procedure, the patients were monitored in a recovery room for at least 2h. They were discharged afterwards, provided there were no signs of complications or complaints. RESULTS: The main indication for DBE was suspected small-bowel bleeding (n=168), and the lesions responsible for the bleeding were found in 123 patients (73 %) and treated in 61 (55 %). In patients with refractory celiac disease (n=25), DBE revealed a high proportion (six patients, 23 %) of enteropathy-associated T-cell lymphomas that had not been suspected on other tests. Further DBE indications were surveillance and treatment of hereditary polyposis syndromes (n=20); and suspected Crohn's disease, which was diagnosed with DBE in four of 13 patients (30 %). No relevant pathology was found in 24 % of the patients. Panenteroscopy was successfully performed in 26 of 62 patients (42 %) in whom it was attempted, in either one or two sessions. The average duration of the procedures was 90 min (range 30 - 180 min, SD 42), and the average insertion length was 270 cm (range 60 - 600 cm, SD 104). Patients' tolerance of the procedure was excellent. Severe complications were recognized in three cases (1 %), all involving pancreatitis. CONCLUSIONS: This large pilot series shows that DBE is a well-tolerated and safe new endoscopic technique with a high diagnostic yield in selected patients.

Adolescent↗
PubMed2002

Variation in the CTLA4/CD28 gene region confers an increased risk of coeliac disease.

Susceptibility to coeliac disease involves HLA and non-HLA-linked genes. The CTLA4/CD28 gene region encodes immune regulatory T-cell surface molecules and is a strong candidate as a susceptibility locus. We evaluated CTLA4/CD28 in coeliac disease by genetic linkage and association and combined our findings with published studies through a meta-analysis. 116 multiplex families were genotyped across CTLA4/CD28 using eight markers. The contribution of CTLA4/CD28 to coeliac disease was assessed by non-parametric linkage and association analyses. Seven studies were identified that had evaluated the relationship between CTLA4/CD28 and coeliac disease and a pooled analysis of data undertaken. In our study there was evidence for a relationship between variation in the CTLA4/CD28 region and coeliac disease by linkage and association analyses. However, the findings did not attain formal statistical significance (p = 0.004 and 0.039, respectively). Pooling findings with published results showed significant evidence for linkage (504 families) and association (940 families): p values, 0.0001 and 0.0014 at D2S2214, respectively, and 0.0008 and 0.0006 at D2S116, respectively. These findings suggest that variation in the CD28/CTLA4 gene region is a determinant of coeliac disease susceptibility. Dissecting the sequence variation underlying this relationship will depend on further analyses utilising denser sets of markers.

Abatacept↗
PubMed2001

Long-term lansoprazole treatment for gastro-oesophageal reflux disease: clinical efficacy and influence on gastric mucosa.

BACKGROUND: Long-term acid suppression is believed to accelerate atrophic gastritis in Helicobacter pylori-positive patients. The influence of long-term therapy with lansoprazole has not been examined. AIM: To study the clinical and endoscopic efficacy and histological evolution of gastric mucosa during 5 years of maintenance treatment with lansoprazole, 30 mg. METHODS: Seventy-eight patients with endoscopically proven oesophagitis were followed for 5 years. Biopsies taken at the start of the study, during follow-up and after 5 years were available for 73 patients. RESULTS: The total endoscopic relapse rate was 14.1%. At the start of the study, 34 patients were Helicobacter pylori negative and 39 were Helicobacter pylori positive (two atrophy, 25 antral gastritis, 12 pangastritis). At 5 years, no histological changes had occurred in Helicobacter pylori-negative patients. In the Helicobacter pylori-positive group, 20 patients developed pangastritis, six had normal histology and one had antral gastritis. Ten of the 12 patients with pangastritis had reduced antral activity. There was no increase in intestinal metaplasia, but there was a tendency towards regression of atrophy in the antrum and towards increased atrophy in the body of the stomach. CONCLUSIONS: Maintenance treatment with lansoprazole, 30 mg, is efficacious. The development of glandular atrophy and intestinal metaplasia was not accelerated in Helicobacter pylori-positive patients. Helicobacter pylori eradication must be considered only because of the higher cancer risk associated with chronic Helicobacter pylori-related gastritis.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2001

A pilot study of recombinant human interleukin-10 in adults with refractory coeliac disease.

Refractory coeliac disease (RCD) is a rare diagnosis made after the exclusion of any disorder mimicking CD and after initial or subsequent failure of a strict gluten-free diet (GFD) to restore normal intestinal architecture. In the past, treatments such as steroids, cyclosporin and azathioprine have been tried, but literature on this subject consists mainly of case reports. Interleukin-10 (IL-10) may be beneficial in RCD because of its inhibitory effect on T-lymphocyte- and monocyte-driven immune responses. We performed a pilot, non-randomized, open label study to evaluate recombinant human IL-10 in RCD. IL-10 (8 mcg/kg) was administered subcutaneously, three times a week for 3 months in 10 RCD patients. Small bowel biopsies were taken at T = 0, T = 3 months and T = 9 months. The mucosal histopathology at 3 months was the primary end point for evaluation of efficacy. Evaluations of clinical features, malabsorption parameters and safety were made prior to, during and after treatment. Before treatment, all RCD patients had partial to total villous atrophy (Marsh III ABC). Two patients dropped out of the study: one because of headaches, the other because of thrombocytopenia. In the remaining eight patients, after 3 months of IL-10 treatment histology was unchanged in five patients, improved in two patients and deteriorated in one patient. Disappearance of villous atrophy was seen in only one patient. Three patients reported a clinical response, i.e. relief of fatigue, abdominal complaints and diarrhoea. After stopping IL-10 treatment the symptoms recurred. The laboratory parameters remained the same during treatment and in follow-up. In conclusion, in our study group of 10 RCD patients, IL-10 in the given dosage was not overall effective in our study group of RCD patients. Two dropped out because of side effects and in only one patient did we see a normalization of villous architecture.

Adult↗
PubMed2001

Gluten challenge in borderline gluten-sensitive enteropathy.

OBJECTIVES: In patients with signs and symptoms of malabsorption, suggestive of gluten-sensitive enteropathy, small intestinal biopsies sometimes only reveal infiltration of lymphocytes into the mucosal epithelium. This infiltrative lesion (Marsh I) is not a definite proof for gluten-sensitive enteropathy. However, in the present study, we aimed to show that a subgroup of these patients could ultimately be identified as being gluten sensitive. METHODS: A total of 38 patients with a Marsh I lesion were subjected to a gluten challenge comprising 30 g of gluten added daily to a normal gluten-containing diet for 8 wk. Before and after the challenge, small intestinal biopsies were taken, and symptoms and signs of malabsorption were scored. RESULTS: In 12 patients we demonstrated a significant change in mucosal histopathology, i.e., subtotal villous atrophy (Marsh IIIB, n = 1), partial villous atrophy (Marsh 3A, n = 6) or infiltrative-crypthyperplastic lesions (Marsh II, n = 5). In the other 26 patients, the small intestinal mucosa remained unchanged. After initiation of a gluten-free diet, follow-up small intestinal biopsies in 12 patients who initially had progressive mucosal pathology after gluten challenge showed normalization of mucosal pathology in seven cases, regression to a Marsh I lesion in four, and to a Marsh II lesion in one. Symptom relief was seen in all 12 patients. Ten of 26 patients without histological response to the gluten challenge were motivated to adhere to a gluten-free diet. Follow-up biopsies revealed unchanged Marsh I lesions in eight patients and normalization (Marsh 0) in two patients. Three patients had follow-up biopsies while on a normal diet. All had unchanged Marsh I lesions. CONCLUSIONS: In the present study we demonstrated that a gluten challenge might be useful in identifying patients as being sensitive to gluten if initial small intestinal biopsies reveal only minor abnormalities.

Adolescent↗
PubMed2001

The tissue transglutaminase gene is not a primary factor predisposing to celiac disease.

OBJECTIVES: The aim of this study was to determine whether the tissue transglutaminase (tTG) gene is a causal factor in the pathogenesis of celiac disease (CD). METHODS: A total of 147 Dutch families with at least one patient with biopsy-proven CD were available for this study. In all patients, CD was diagnosed according to the revised European Society for Pediatric Gastroenterology and Nutrition criteria. A microsatellite marker in a noncoding region of the tTG gene was investigated for both linkage and association. Linkage was tested by determining the amount of allele sharing between affected brothers and sisters (affected sibling [sib] pair analysis). Association was determined by comparing transmission of certain tTG alleles from parents to CD patients to the nontransmitted alleles by the transmission/disequilibrium test. RESULTS: Linkage analysis did not show cosegregation of the tTG gene with celiac disease in our families, and there was no association between certain tTG alleles and celiac disease. Furthermore, the tTG gene could be excluded as a CD susceptibility gene. CONCLUSION: Our results indicate that the tTG gene can be excluded as a major primary genetic factor in CD pathogenesis.

Adult↗
PubMed2000

Sensitivity of a hyperosmolar or "low"-osmolar test solution for sugar absorption in recognizing small intestinal mucosal damage in coeliac disease.

Reliability of differential sugar absorption tests is hampered by a lack of standardization of the content and osmolarity of the test solutions. We evaluated the effect of osmolarity of the test solution of the sugar absorption test on the 5 hour urine excretion of orally administered lactulose and mannitol. A group of 28 controls and 14 coeliacs, with villous atrophy grade II to IV, ingested a hyperosmolar sugar absorption test solution and a "low"-osmolar solution, respectively. After an overnight fast, each subject ingested hyperosmolar sugar absorption test solution (2 g mannitol, 5 g lactulose and 40 g sucrose/100 ml (around 1,560 mmol/l)). After two days, this procedure was repeated with low-osmolar solution (2 g mannitol and 5 g lactulose/100 ml (around 375 mmol/l). The influence of the sequence of the tests on the results had previously been excluded. All urine from the 5 h-period following ingestion of the test solution was collected. To calculate the low-osmolar solution ratio, samples were analysed for lactulose and mannitol concentrations by gas chromatography The sensitivity of hyperosmolar SAT solution and low-osmolar solution for the detection of mucosal abnormalities in coeliacs was 64% and 43%, respectively. In conclusion, a hyperosmolar solution discriminates better between normal and damaged mucosa of the small bowel such as villous atrophy due to a relative increase in permeability for lactulose.

Administration, Oral↗
PubMed2000

Cyclosporin in the treatment of adults with refractory coeliac disease--an open pilot study.

AIM: To evaluate the effect of cyclosporin treatment on clinical and histological parameters in adult patients with refractory coeliac disease. METHODS: Thirteen patients were treated with oral cyclosporin for 2 months, aiming at serum levels of 100-200 ng/mL. Seven extended medication intake up to a maximum of 12 months. Before and after treatment, clinical parameters were monitored and small intestinal biopsies taken. Ten of 13 patients were typed for HLA-DQA1 and -DQB1 alleles. RESULTS: Eight of 13 patients responded histologically to cyclosporin treatment. Normalization of villi was demonstrated in five patients, three after prolonged treatment. Eight patients reported a clinical response, of whom six had concomitant histological improvement. No serious side-effects of cyclosporin were noticed. Nine of 10 patients who were immunogenetically typed carried the coeliac disease associated serologic DQ2 markers, one carried neither DQ2 nor DQ8 markers. CONCLUSION: In our study group of 13 adult refractory coeliac disease patients, cyclosporin in therapeutic doses induced a histological improvement in eight patients (61%), in five of whom (38%) normalization of villi was demonstrated. Thus, we believe that cyclosporin is a therapeutic option in refractory coeliac disease, although we could not confirm earlier reports of unconditional successful treatment.

Adult↗
PubMed2000

A randomized trial of polyurethane and silicone percutaneous endoscopic gastrostomy catheters.

BACKGROUND: No data are available on differences in complication rate and long-term functioning between polyurethane and silicone percutaneous endoscopic gastrostomy (PEG) catheters. METHODS: We randomized patients who qualified for PEG placement to receive either a polyurethane or silicone PEG catheter. Patients were prospectively monitored for 28 days after placement for the occurrence of complications. Data on long-term PEG survival were obtained retrospectively from the Hospital and general practitioner's medical records. RESULTS: One hundred and six patients were randomized (polyurethane 50, silicone 56). During the first four weeks of follow-up, major complications occurred twice with both polyurethane and silicone PEGs (relative risk 1.1, 95% confidence interval: 0.11-11). Overall complications occurred four times with polyurethane and 17 times with silicone PEGs (relative risk 3.8, 95% confidence interval: 1.37-10.5). Long-term follow-up was available in 96 patients. Seven polyurethane PEGs and 10 silicone PEGs were removed because of PEG malfunctioning, the remainder functioned well until death or the reinstitution of oral feeding. The median complication-free survival was 916 days for the polyurethane PEG and 354 days for the silicone PEG (Log rank test: P=0.24). CONCLUSION: Polyurethane PEG catheters were associated with less short-term complications than silicone catheters, but major complications and long-term function were comparable.

Adolescent↗
PubMed2000

Should relatives of coeliacs with mild clinical complaints undergo a small-bowel biopsy despite negative serology?

BACKGROUND AND OBJECTIVES: Small intestinal lesions in coeliac disease (CD) have a variable severity. Early diagnosis of CD is important because treatment allows a normal psycho-physical development, especially in children, and can avoid associated disorders. The aim of this study was to evaluate the predictive value of screening parameters for the detection and estimation of CD prevalence in first-degree relatives. METHODS: The screening was performed in 338 first-degree relatives of 134 coeliac families. Questionnaires and a physical examination followed by haematological analyses and serologyfor IgA anti-endomysium (EMA)/IgA antigliadin (AGA) antibodies were used in orderto selectthe candidates for small-bowel biopsy. The small-bowel biopsy was indicated on the basis of clinical complaints, laboratory tests and serology performed in 96 (28%) of the study group. RESULTS: CD was diagnosed in 17/96 cases. Six of the 17 showed total villous atrophy (VA) (Marsh IIIc), five subtotal VA (Marsh IIIb) and six partial VA (Marsh IIIa). EMA and AGA were strongly positive in the six patients whose intestinal biopsy showed total VA. However, only one coeliac out of the six patients with partial VA had positive EMA and AGA. CONCLUSION: A significant proportion of coeliacs may be missed if cases are screened by serology only. Although endomysial antibody assay has been reported as a highly sensitive and specific test for detection of CD, we argue that using only EMA and AGA in screening is not enough for investigation of the true prevalence of CD. A combination of clinical parameters as described in this study and laboratory/serological tests is an important and practical contribution to improving the detection rate of CD.

Adolescent↗
PubMed2000

Refractory coeliac disease: a window between coeliac disease and enteropathy associated T cell lymphoma.

The treatment of coeliac disease (CD) is straightforward and simple: life-long adherence to a gluten-free diet. However, in a small subgroup of patients, the clinical and histological abnormalities persist or recur. This non-responsiveness leaves a poorly understood syndrome known as refractory coeliac disease (RCD). A specific definition of RCD is lacking in the literature. We speculate that RCD may appear in a subgroup of coeliacs with persisting histologic abnormalities. In all patients screened for RCD we look for DQ2 and DQ8. In non-DQ2/DQ8 patients we reconsider the diagnosis of CD and of auto-immune enteropathy. Most of the patients referred to us because of suspicion of RCD are affected by other diseases. Probably the commonest cause of non-responsiveness is continued gluten intake. Exocrine pancreas insufficiency, hyperthyroid disease, collagenous colitis are other common explanations. RCD and enteropathy-associated T cell lymphomas (EATL) can be distinguished by intra-epithelial lymphocyte phenotyping and TCR-gamma gene rearrangements. In RCD, an unexplained sustained stimulation of T cell cytotoxic activity is present. Immunosuppressive treatment might moderate this. Cyclosporine has been reported as a resounding success in case reports; however, our results were disappointing. We suggest azathioprine and steroids in RCD without aberrant T-lymphocytes in their mucosa. However, in RCD with aberrant T-lymphocytes we suggest chemotherapy. As the prognosis of EATLs is extremely poor the early detection of RCD with aberrant T cells is crucial.

CD8 Antigens↗
PubMed1999

Polymorphic expression of the glutathione S-transferase P1 gene and its susceptibility to Barrett's esophagus and esophageal carcinoma.

Factors determining individual susceptibility to esophageal cancer or premalignant Barrett's epithelium are still largely unclear. An imbalance between phase I drug metabolism [e.g., cytochrome P450 (CYP)] and phase II detoxification [e.g., glutathione S-transferase (GST)] may contribute to the development of these diseases. Polymorphic variants in the CYP1A1 gene were described leading to increased levels of bioactive compounds, whereas polymorphisms in GST genes often resulted in impaired detoxification. We studied the frequencies of polymorphic variants in CYP1A1, GSTP1, GSTT1, and GSTM1 genes in 98 patients with Barrett's epithelium and 34 patients with esophageal cancer. The results were compared with those obtained from 247 healthy blood donors. DNA was extracted, and PCR-RFLP methods were used to detect genetic polymorphisms. Chi2 analysis, Spearman rank correlation, and Wilcoxon rank sum tests were used for statistical evaluation. Polymorphisms in CYP1A1, GSTM1, and GSTT1 occurred at an equal frequency in patients and controls. Occurrence of the polymorphic GSTP1b variant in the GSTP1 gene resulted in a significantly lower GST enzyme activity (P < 0.05), and GSTP1b was found significantly more often in patients with Barrett's epithelium (70%; P < 0.001) and patients with esophageal adenocarcinoma (76%; P = 0.005), as compared to healthy blood donors (41%). In conclusion, presence of the GSTP1b allele leads to lower GST enzyme activity levels and, consequently, impaired detoxification. This most important esophageal GST isoform may, therefore, contribute to the development of Barrett's epithelium and adenocarcinoma.

Adenocarcinoma↗
PubMed1999

[Intraluminal therapy for Zenker's diverticulum].

A Zenker's diverticulum (ZD) is a posterior diverticulum with its neck proximal to the cricopharyngeal muscle. Patients typically present after the age of 60 with symptoms ranging from weeks to years. The classical treatment in the past was surgical, which is still the case in the US. They treat them in general with open myotomy and diverticulectomy. Since the 1950s ENT physicians treat them with rigid endoscopes and cut the bridge between the ZD and the esophagus. This method is widely used throughout western Europe. However, many symptomatic elderly patients are poor surgical/ENT candidates. In 1995, two groups from Brazil and The Netherlands reported their first results with a gastroscopic treatment, in which the ZD bridge is cut with a precut needle/monopolar forceps. Recently, argon plasma coagulation has also been introduced in this field. All these treatments seem effective. Comparative trials between these approaches are now long overdue, since all these modalities will work in the hands of experienced "Zenker specialists".

Argon↗