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Biomedical subjects

C J J Mulder

Publications and source records attributed to C J J Mulder.

At least 19 recordsLinked to original sources
PubMed2006

On attitudes about colorectal cancer screening among gastrointestinal specialists and general practitioners in the Netherlands.

AIM: To find out whether there are differences in attitudes about colorectal cancer (CRC) screening among gastrointestinal (GI) specialists and general practitioners (GPs) and which method is preferred in a national screening program. METHODS: Four hundred and twenty Dutch GI specialists in the Netherlands and 400 GPs in Amsterdam were questioned in 2004. Questions included demographics, affiliation, attitude towards screening both for the general population and themselves, methods of screening, family history and individual risk. RESULTS: Eighty-four percent of the GI specialists returned the questionnaire in comparison to 32% of the GPs (P < 0.001). Among the GI specialists, 92% favoured population screening whereas 51% of GPs supported population screening (P < 0.001). Of the GI specialists 95% planned to be screened themselves, while 30% of GPs intended to do so (P < 0.001). Regarding the general population, 72% of the GI specialists preferred colonoscopy as the screening method compared to 27% of the GPs (P < 0.001). The method preferred for personal screening was colonoscopy in 97% of the GI specialists, while 29% of the GPs favoured colonoscopy (P < 0.001). CONCLUSION: Screening for CRC is strongly supported by Dutch GI specialists and less by GPs. The major health issue is possibly misjudged by GPs. Since GPs play a crucial role in a successful national screening program, CRC awareness should be realized by increasing knowledge about the incidence and mortality, thus increasing awareness of the need for screening among GPs.

Aged↗
PubMed2006

6-Thioguanine treatment in inflammatory bowel disease: a critical appraisal by a European 6-TG working party.

Recently, the suggestion to use 6-thioguanine (6-TG) as an alternative thiopurine in patients with inflammatory bowel disease (IBD) has been discarded due to reports about possible (hepato) toxicity. During meetings arranged in Vienna and Prague in 2004, European experts applying 6-TG further on in IBD patients presented data on safety and efficacy of 6-TG. After thorough evaluation of its risk-benefit ratio, the group consented that 6-TG may still be considered as a rescue drug in stringently defined indications in IBD, albeit restricted to a clinical research setting. As a potential indication for administering 6-TG, we delineated the requirement for maintenance therapy as well as intolerance and/or resistance to aminosalicylates, azathioprine, 6-mercaptopurine, methotrexate and infliximab. Furthermore, indications are preferred in which surgery is thought to be inappropriate. The standard 6-TG dosage should not exceed 25 mg daily. Routine laboratory controls are mandatory in short intervals. Liver biopsies should be performed after 6-12 months, three years and then three-yearly accompanied by gastroduodenoscopy, to monitor for potential hepatotoxicity, including nodular regenerative hyperplasia (NRH) and veno-occlusive disease (VOD). Treatment with 6-TG must be discontinued in case of overt or histologically proven hepatotoxicity.

Antimetabolites, Antineoplastic↗
PubMed2006

Chemoprevention for colon cancer: new opportunities, fact or fiction?

Colorectal cancer (CRC) is still a disease with a high incidence and mortality. Prevention of (pre-) cancerous lesions of CRC by endoscopic screening is promising, but costs are high and identification of high-risk populations is difficult. Since screening both average-risk and high-risk populations for CRC has its logistic and financial limitations, new primary prevention strategies are sought. Substantial evidence has shown that non-steroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors can reduce the incidence and mortality of CRC. However, long-term use of NSAIDs is associated with substantial gastrointestinal toxicity and may cause an exacerbation in IBD patients. Selective COX-2 inhibitors, with a better toxicity profile and no flare-up in IBD disease activity, are therefore attractive candidates for prevention. Chemoprevention with low-dose aspirin can be considered for individuals carrying a high risk for CRC. Folate supplementation is beneficial to the folate-depleted patients, since significant risk reductions for CRC are reported. Moreover, it might be applicable to the general population because it is safe, inexpensive and protects against vascular diseases. In line with drugs beneficial for multiple disease entities, statins have recently been proposed to reduce CRC risk. Ursodeoxycholic acid has been shown to decrease the incidence of colonic dysplasia in patients with ulcerative colitis and PSC and possibly reduces recurrence rates of polyps in general. Unfortunately, prospective randomized trials, in both high-risk and general population, are not available and the evidence is still controversial. Furthermore, cumulative epidemiological and observational data suggest the potential role of hormones as a chemoprotective agent. An increase in CRC in females with an early menopause, as well as a decrease of CRC in women with hormone replacement therapy justify further research into this issue. In IBD patients, both the severity and duration of the inflammation are the most evident risk factors for the development of dysplasia and subsequently cancer. Remission of inflammation, clinically, endoscopically and histologically, in IBD is the major goal. Long-term use of 5-aminosalicylates (5-ASA) has been shown to decrease the incidence of CRC and may hold the best promise as a chemoprotective agent in IBD. In parallel with primary prevention strategies in vascular medicine, the aim might be to postpone adenoma formation, for instance for 10 years, thereby achieving a significant risk reduction for CRC. In current practice, folate supplementation along with low-dose aspirin use in high-risk patients may be most attractive candidates, while future studies will have to clarify the role of these and other chemoprotective agents.

Age Factors↗
PubMed2006

Milestone in gastrointestinal endoscopy: double-balloon enteroscopy of the small bowel.

The small bowel (SB) has been largely bypassed by flexible endoscopy because of inaccessibility. Push enteroscopy is now in the past, with recent innovations now making visualization of the SB possible. Wireless capsule endoscopy (CE) and double-balloon endoscopy (DBE) have been introduced. In this review, we focus on the diagnostic and therapeutic modalities of DBE, which may be a suitable replacement for push enteroscopy, preoperative endoscopy and to some extent of SB fall-through and CT scan. DBE is a new method of endoscopy developed and described by Yamamoto et al. in Jichi, Japan, in cooperation with Fujinon. Introduced to the market in 2003, it is possible with this endoscope to observe the entire SB in steps of 20-40 cm. Measuring the depth of insertion is also possible. Obscure gastrointestinal bleeding can be explained and treated in the majority of cases. Biopsy sampling, hemostasis, polypectomy, dilatation and tattoo are possible in the SB. Guidelines for FAB and Peutz-Jeghers syndrome will probably be reviewed in the next few years. The safety and efficacy of DBE have been demonstrated. DBE improves SB disease management and can substitute for more complex investigations. Additional data will come to light in years to come. Combining DBE with CE, CT/MRI enteroclysis in a new era for SB work-up and treatment is the likely future.

Catheterization↗
PubMed2006

Dutch endoscopic capacity in the era of colorectal cancer screening.

BACKGROUND: Future colorectal cancer (CRC) screening programmes should not (greatly) interfere with regular health care. Hence, we analysed the Dutch endoscopic practice to provide a clear insight into endoscopic workload and manpower with a special emphasis on the current ability to facilitate a successful implementation of a faecal occult blood test (FOBT)-based nationwide CRC screening programme. METHODS: A questionnaire was sent to all Dutch endoscopy units (n = 100) in the spring of 2005. The questionnaire included topics ranging from the numbers and specifications of endoscopies performed in 2004 and the numbers of endoscopists per unit to expected vacancies for gastroenterologists and waiting times. RESULTS: The response rate was 98%, representing a total of 49,253 hospital beds. overall, a 26% increase in the number of endoscopies from 325,000 in 1999 to almost 410,000 in 2004 was found, accompanied by a 25% increase in manpower. The total number of endoscopists was 598. regional differences were observed in the number of endoscopists, the total number of endoscopies and colonoscopies, and the number of endoscopies per endoscopist. A biannual FOBT-based screening programme would yield an additional workload of 25,385 colonoscopies a year amounting to a 22% increase in the total number of colonoscopies performed. However, the workload per unit would only have to increase by five extra colonoscopies a week. CONCLUSION: Whereas an FOBT-based CRC screening programme is currently feasible without strongly interfering with regular health care, future plans regarding the scale and preferred mode of screening should incorporate solid data on the (regional) endoscopic capacity and manpower needed for a successful implementation.

Colorectal Neoplasms↗
PubMed2005

[Palliative treatment of esophageal cancer with dysphagia: more favourable outcome from single-dose internal brachytherapy than from the placement of a self-expanding stent; a multicenter randomised study].

OBJECTIVE: To compare the results of single-dose internal irradiation (brachytherapy) and self-expanding metal stent placement in the palliation of oesophageal obstruction due to cancer of the oesophagus. DESIGN: Randomised trial. METHOD: In the period from December 1999-Jun 2002, 209 patients with dysphagia due to inoperable carcinoma of the oesophagus were randomised to placement of an Ultraflex stent (n = 108) or single-dose (12 Gy) brachytherapy (n = 101). Primary outcome was relief of dysphagia; secondary outcomes were complications, persistent or recurrent dysphagia, health-related quality of life, and costs. Patients were followed up by monthly home visits from a specialised nurse. RESULTS: Dysphagia improved more rapidly after stent placement than after brachytherapy, but long-term relief of dysphagia was better after brachytherapy. Stent placement resulted in more complications than did brachytherapy (36/108 (33%) versus 21/101 (21%); p = 0.02), due mainly to an increased incidence of late haemorrhage in the stent group (14 versus 5; p = 0.05). The groups did not differ with regard to the incidence of persistent or recurrent dysphagia or median survival (p > 0.20). In the long term, quality-of-life scores were higher in the brachytherapy group. Total medical costs were also similar for both treatments: Euro 8,215 for stent placement and Euro 8,135 for brachytherapy. CONCLUSION: Brachytherapy provided better long-term relief of dysphagia than did stent placement and also produced fewer complications. Brachytherapy is therefore recommended as the preferred treatment for the palliation of dysphagia due to oesophageal cancer.

Aged↗
PubMed2005

On the limitation of 6-tioguaninenucleotide monitoring during tioguanine treatment.

BACKGROUND: Tioguanine (thioguanine) has been proposed as a rescue thiopurine for azathioprine or mercaptopurine intolerant inflammatory bowel disease patients. The use of tioguanine leads to high 6-tioguaninenucleotide (6-thioguaninenucleotide) levels in red blood cells but, contra-intuitively, these have yet not been associated with an increased risk of myelotoxicity. AIM: To assess the role of 6-tioguaninenucleotide concentrations in developing myelotoxicity during tioguanine treatment. METHODS: Database analysis of 25 patients treated with tioguanine. Clinical findings and laboratory parameters were related to 6-tioguaninenucleotide levels. RESULTS: One patient developed a myelodepression (21 mg TG/day for 3 months and 6-tioguaninenucleotide 714 pmol/8 x 10(8) red blood cells). 6-Tioguaninenucleotide levels varied greatly between individuals (mean 6-tioguaninenucleotide level 621 pmol/8 x 10(8) red blood cells, s.d. 340 pmol/8 x 10(8) red blood cells and range 34-1653 pmol/8 x 10(8) red blood cells). The TG dosages (mean 20.6 mg/day and median 20 mg/day) did not correlate with 6-tioguaninenucleotide levels (r = 0.31, N.S.). High 6-tioguaninenucleotide levels (>450 pmol/8 x 10(8) red blood cells) did not effect haemoglobin concentrations (mean 8 mmol/L), peripheral leucocyte (mean 7.5 x 10(9)/L) or platelet counts (mean 298 x 10(9)/L). No correlations were established between laboratory parameters, type of disease and 6-tioguaninenucleotide level. CONCLUSION: High 6-tioguaninenucleotide levels in erythrocytes (>450 pmol/8 x 10(8)) during TG treatment compared to azathioprine or mercaptopurine treatment are not indicative for (developing) myelotoxicity.

Adult↗
PubMed2005

[Clinical reasoning and decision-marking in practice. A general practitioner with long-standing anaemia].

In order to calibrate his haemoglobin meter, a general practitioner had his own haemoglobin level checked regularly at a nearby laboratory. At 37 years of age, one of these assays revealed 7,0 mmol/l. Because he had no symptoms, he prescribed himself iron-substitution therapy but the haemoglobin concentration did not normalise. At 52 years of age, the patient increasingly suffered from fatigue and exertional dyspnoea and had intermittent abdominal pain, distension and rumbling. Biopsies of the small intestine revealed crypt hypertrophy and intraepithelial lymphocytosis: signs ofcoeliac disease. The symptoms disappeared when the patient started to use a gluten-free diet. The haemoglobin level also normalised. Coeliac disease must be considered in the differential diagnosis of iron-deficiency anaemia.

Adult↗
PubMed2005

Coeliac disease: changing views.

A continuing flow of new scientific developments concerning coeliac disease in the last decade asks for the formulation of new concepts of pathophysiology and clinical considerations. Immunogenetic studies have shown a correlation of the disease to the HLA region on the short arm of chromosome 6, immunological research has led to the concept of a T-cell driven immunologic response of the small intestine, with the identification of highly sensitive and specific antibodies. The understanding of the histopathology of coeliac disease has changed dramatically, initiated by the proposition of a spectrum of gluten sensitive enteropathy by Marsh in 1992. Clinical studies report a significant change in patient characteristics and epidemiology. The incidence of the disease has shifted to a majority of adult coeliacs, the disease may present with less severe symptoms of malabsorption and the screening studies suggest an overall prevalence of up to 1 in 200-300. Histopathology has been standardized; lymphocytic enteritis (Marsh I), lymphocytic enteritis with crypthyperplasia (Marsh II), and villous atrophy, subdivided in partial, subtotal and total (Marsh IIIABC). Special attention is given to a subgroup of 'refractory coeliacs', including the identification of pre-malignant T-cells in the intestinal mucosa. The management of coeliacs primarely consists of monitoring for compliance and complications. Dietetic and medical associations need to establish protocols and offer additional training to undergraduetes, internships, general practitioners and other allied health professionals. It might be relevant to have a low threshold for intestinal biopsies. However, screening asymptomatics may be harmful for individuals. Research is needed to assess the benefits of mass-screening in the future. HLA analysis can contribute towards recognising populations at increased risk.

Celiac Disease↗
PubMed2005

Thiopurines in inflammatory bowel disease: pharmacogenetics, therapeutic drug monitoring and clinical recommendations.

There is a growing interest in the use of thiopurines (azathioprine, 6-mercaptopurine and 6-thioguanine) for the management of inflammatory bowel disease. The genetically controlled thiopurine (S)-methyltransferase enzyme is involved in the metabolism of these agents and is hypothesised to determine the clinical response to thiopurines. Diminished activity of this enzyme decreases the methylation of thiopurines, theoretically resulting in potential overdosing, while high thiopurine (S)-methyltransferase status leads to overproduction of toxic metabolites and ineffectiveness of azathioprine and 6-mercaptopurine. In practice, controversies exist regarding the utility of standard thiopurine (S)-methyltransferase pheno- and genotyping. Current pharmacogenetic insights suggest that another enzyme system may participate in the efficacy and toxicity of thiopurines; inosine triphosphate pyrophosphatase. Other topics discussed in this review are the utilisation of therapeutic drug monitoring and the experimental use of 6-thioguanine in the treatment of inflammatory bowel disease. 6-Thioguanine has a less genetically controlled metabolism and skips genetically determined metabolic steps. On theoretical basis, 6-thioguanine might therefore have a more predictable profile than azathioprine and 6-mercaptopurine. However, the use of 6-thioguanine has been associated with an increased risk of nodular regenerative hyperplasia of the liver and veno-occlusive disease. Further research is warranted before 6-thioguanine can be considered as a treatment option for inflammatory bowel disease.

Antimetabolites↗
PubMed2005

A NFKB1 promoter polymorphism is involved in susceptibility to ulcerative colitis.

Nuclear factor kappaB (NF-kappaB) designates a group of critical transcription factors involved in a variety of immunologic and/or inflammatory processes. Conceivably, genes involved in the NF-kappaB pathway make interesting candidate genes for chronic inflammatory disorders, including the inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC). In two mouse models of colitis, strong linkage has been observed with a locus on chromosome 3 that harbours the Nfkb1 gene. In addition, a polymorphism in the promoter region of the human NFKB1 gene was found to be associated with susceptibility to UC. In this study, we searched to confirm this previously found association in IBD in a different population. Allele and genotype frequencies of the -94 ins/delATTG polymorphism were determined in 266 unrelated Dutch Caucasian IBD patients (127 UC, 139 CD), and 155 matched healthy controls. The allele frequency of the deletion was significantly higher in UC patients (P = 0.019), but not in CD patients, compared to healthy controls, and the UC patients homozygous for the -94 ATTG deletion had a younger age of onset. Our findings confirm the previously found association between this polymorphism and susceptibility to UC in an independent study population and adds further evidence for the role of this gene in disease susceptibility.

Adult↗
PubMed2005

Myelotoxicity and hepatotoxicity during azathioprine therapy.

Azathioprine is a frequently used immunosuppressant for managing inflammatory bowel disease (IBD). In recent years the hepatotoxic profile of thiopurines has been recognised. We report the case of a 40-year-old man with Crohn's disease treated with azathioprine. After taking azathioprine (2.2 mg/kg daily) for two years, his liver function tests were found to be elevated. Moreover, a myelodepression was established as platelet and leucocytes counts were lowered. The 6-thioguaninenucleotide level was 738 picomoles/8 x 10(8) per red blood cell, which is well above the proposed upper limit of efficacy and associated with an increased risk of developing a myelodepression. Genotyping of the enzyme thiopurine methyltransferase revealed no mutant alleles. The ultrasonography and CT scan showed signs of portal hypertension (spleen 17 cm and widened splenic vein). A liver biopsy was performed and an incomplete septal liver cirrhosis was found. An upper endoscopy revealed oesophageal varices (grade 2 to 3). Autoimmune and viral liver diseases were ruled out by laboratory parameters. After cessation of therapy, all laboratory parameters normalised. Therefore, azathioprine is believed to be the causative factor for inducing the liver cirrhosis. Continuous monitoring of patients taking thiopurines is mandatory. The role of 6-thioguaninenucleotide levels in inducing myelotoxicity and hepatotoxicity is discussed.

Adult↗
PubMed2004

Association of FAS (TNFRSF6)-670 gene polymorphism with villous atrophy in coeliac disease.

AIM: To investigate the association of FAS gene polymorphism with coeliac disease (CD) development. METHODS: FAS-G670A gene polymorphism, located in a gamma interferon activation site, was studied in 146 unrelated CD patients and 203 healthy ethnically matched controls. The restriction fragment length polymorphism (RFLP) method was used to identify FAS-G670A gene polymorphism. RESULTS: No significant difference was found in genotype frequency between CD cases and controls. In controls, however, the frequency of the GG genotype was significantly higher in women (26.5%) than in men (12.8%) (OR= 2.44, 95% CI 1.15-5.20, P=0.020) and it was also higher in men with CD than controls (OR=2.60, 95% CI 0.96-7.05, P=0.061). The GG genotype frequency was significantly higher in patients with most severe villous atrophy (Marsh IIIc lesions) (OR=3.74, 95% CI 1.19-11.82, P=0.025). A significantly less proportion of men suffered from Marsh IIIc lesions than women (OR=0.20, 95% CI 0.06-0.68, P=0.01). The risk of having severe villous atrophy increased with the additive effect of the G allele in women (P=0.027 for trend, age and gender adjusted). CONCLUSION: FAS-G670A gene polymorphism is associated with the severity of villous atrophy in CD. Female gender is also associated with the severity of villous atrophy.

Atrophy↗
PubMed2004

Coeliac disease and (extra)intestinal T-cell lymphomas: definition, diagnosis and treatment.

Intestinal lymphomas encompass those lymphomas with a dominant or only localized occurrence in the intestinal tract. Coeliac disease is highly associated with enteropathy-associated T-cell lymphomas (EATLs). Coeliac disease-related lymphomas can appear at nodal or extranodal sites. EATL is often multifocal with ulcerative lesions, which explains the high perforation rate at presentation or during chemotherapy. Staging includes ear-nose-throat examination and CT scan of the chest and abdomen. Positron emission tomography (PET) scanning may be valuable. Accurate diagnosis based on endoscopic biopsies is preferable; if necessary, full thickness laparoscopic small-bowel biopsies are mandatory. Refractory coeliac disease (RCD) with aberrant T cells carries a high risk of development of EATLs. There is no satisfactory treatment for EATL, the only possibility of preventing EATL development in RCD being autologous bone marrow transplantation. EATLs can present in 20% of patients as extra-small-bowel T-cell lymphomas; such as subcutaneous panniculitis-like lymphoma, hepatosplenic gamma/delta lymphoma, nodal as well as sinus, gastric or colon disease and extraintestinal T-cell lymphomas. The majority of EATLs present as large cell lymphoma CD3+, CD8-, CD30+; however, they also present as small cell lymphoma CD3+, CD8+, CD30-. Sometimes gamma/delta lymphomas in CD are recognized. Work-up of EATL must include immunohistology, T-cell flow cytometry, T-cell rearrangement and adequate imaging with CT and PET scanning.

Celiac Disease↗
PubMed2004

A microarray screen for novel candidate genes in coeliac disease pathogenesis.

BACKGROUND AND AIMS: The causative molecular pathways underlying the pathogenesis of coeliac disease are poorly understood. To unravel novel aspects of disease pathogenesis, we used microarrays to determine changes in gene expression of duodenal biopsies. METHODS: cDNA microarrays representing 19 200 genes were used to compare gene expression profiles of duodenal biopsies from 15 coeliac disease patients with villous atrophy (Marsh III) and seven control individuals with normal biopsies (Marsh 0). In addition, the specific effect of gluten was studied by comparing the expression profiles of Marsh III lesions of seven patients exposed to gluten with four patients on a gluten free diet. RESULTS: Comparing Marsh III with Marsh 0 lesions identified 109 genes that differed significantly (p<0.001) in expression levels between patients and controls. A large number of these genes have functions in proliferation and differentiation pathways and might be important for correct development of crypt-villous units. Alterations in these pathways may lead to the characteristic hyperplasia and villous atrophy seen in coeliac disease. The analyses also revealed 120 differentially expressed genes (p<0.005) when comparing patients on a gluten free diet with those exposed to gluten. These genes further strengthen our observation of increased cell proliferation in the presence of gluten. CONCLUSIONS: Our study provides new candidate genes in the pathogenesis of coeliac disease. Based on our results, we hypothesise that villous atrophy in coeliac disease patients is due to failure in cell differentiation. These genes are involved in pathways not previously implicated in coeliac disease pathogenesis and they may provide new targets for therapy.

Adult↗