G den Hartog

Rijnstate Hospital, Arnheim, Gelderland, Netherlands

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Publications (16)37.85 Total impact

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    ABSTRACT: The use of 6-thioguanine has been proposed as a rescue drug for inflammatory bowel disease patients. Initial data on short-term efficacy and toxicity of 6-thioguanine were promising; however, these have been challenged by reports concerning its potential hepatotoxic effect (nodular regenerative hyperplasia). We proposed that these histological liver abnormalities may well be dose- or level-dependent. We performed a prospective multi-centre study on the hepatotoxic potential of long-term and (as compared with prior studies) low-dose 6-thioguanine use. Inflammatory bowel disease patients using 6-thioguanine for at least 30 consecutive months and consenting to undergo a liver biopsy were enrolled. Liver biopsy specimens were scored by two pathologists, unaware of clinical data. Laboratory parameters, determined prior to initiation of 6-thioguanine therapy and prior to biopsy, were reviewed. Twenty-eight biopsies were analysed. The majority of patients (89%) were azathioprine and/or 6-mercaptopurine intolerant inflammatory bowel disease patients. In 26 patients (93%) no signs of nodular regenerative hyperplasia were detected; in two additional patients nodular regenerative hyperplasia could not be excluded due to inconclusive pathological findings. The mean 6-thioguanine dosage, 6-thioguaninenucleotides level, duration of use and cumulative dosage were 19.5mg, 564 pmol/8 x 10(8) RBC, 38 months and 22491 mg, respectively. We have demonstrated that low-dose 6-thioguanine maintenance therapy in inflammatory bowel disease patients is not likely to be associated with induction of nodular regenerative hyperplasia. The induction of nodular regenerative hyperplasia appears to be 6-thioguanine dose or 6-thioguaninenucleotides level dependent.
    Digestive and Liver Disease 03/2008; 40(2):108-13. · 3.16 Impact Factor
  • Journal of Crohn's and Colitis Supplements. 01/2007; 1(1):22-22.
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    ABSTRACT: (13)Carbon urea breath testing is reliable to detect current infection with Helicobacter pylori but has been reported to be of limited value in selected patients with atrophic body gastritis or acid-lowering medication. To evaluate the accuracy of (13)carbon urea breath testing for H. pylori detection in 20 asymptomatic patients with histologically confirmed atrophic body gastritis in a primary care setting. (13)Carbon urea breath testing and serology were compared with H. pylori culture of a corpus biopsy as reference test. All tests were in agreement in 12 patients, being all positive in six and all negative in six. One patient was positive for serology and culture but negative for (13)carbon urea breath testing, five patients had only positive serology and two patients had only positive (13)carbon urea breath testing. (13)Carbon urea breath testing showed an accuracy with culture of 85% and anti-H. pylori serology with culture of 75%. (13)Carbon urea breath testing carried out in patients with positive serology showed an accuracy of 92%. Receiver operating characteristic curve analysis of (13)carbon urea breath testing shows optimal discrimination at the prescribed cut-off value. (13)Carbon urea breath testing can be used as diagnostic H. pylori test in asymptomatic patients with atrophic body gastritis, preferably in addition to serology, to select subjects for anti-H. pylori therapy.
    Alimentary Pharmacology & Therapeutics 09/2006; 24(4):643-50. · 4.55 Impact Factor
  • European Journal of Gastroenterology & Hepatology - EUR J GASTROENTEROL HEPATOL. 01/2006; 18(1).
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    ABSTRACT: To determine the tolerability and safety profile of a low-dose maintenance therapy with 6-TG in azathioprine (AZA) or 6-mercaptopurine (6-MP) intolerant inflammatory bowel disease (IBD) patients over a treatment period of at least 1 year. Database analysis. Twenty out of ninety-five (21%) patients discontinued 6-TG (mean dose 24.6 mg; mean 6-TGN level 540 pmol/8 x 10(8) RBC) within 1 year. Reasons for discontinuation were GI complaints (31%), malaise (15%) and hepatotoxicity (15%). Hematological events occurred in three patients, one discontinued treatment. In the 6-TG-tolerant group, 9% (7/75) could be classified as hepatotoxicity. An abdominal ultrasound was performed in 54% of patients, one patient had splenomegaly. The majority of AZA or 6-MP-intolerant IBD patients (79%) is able to tolerate maintenance treatment with 6-TG (dosages between 0.3 and 0.4 mg/kg per d). 6-TG may still be considered as an escape maintenance immunosuppressant in this difficult to treat group of patients, taking into account potential toxicity and efficacy of other alternatives. The recently reported hepatotoxicity is worrisome and 6-TG should therefore be administered only in prospective trials.
    World Journal of Gastroenterology 10/2005; 11(35):5540-4. · 2.55 Impact Factor
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    ABSTRACT: Measurement of the serum concentration of the secretory products of the gastric mucosa, pepsinogen A (PgA), pepsinogen C (PgC) and gastrin is called the serological gastric biopsy. Additional measurement of Helicobacter pylori antibodies and antibodies to parietal cells and intrinsic factor supports the non-invasive diagnostic value of the serum markers. In many clinical studies, the diagnostic potential of the serum markers in predicting the topography and severity of gastric mucosal disorders has been established. The aim was to assess the diagnostic value of the serological gastric biopsy for primary care. Survey of the literature. The cell-physiological background of the serological gastric biopsy, the interpretation of the outcome of serum markers and the relation of these parameters to various gastric mucosal disorders are described. Measurement of PgA is a reliable way to discriminate between mucosal gastritis and functional dyspepsia. PgA is raised in duodenal, gastric and pyloric ulcer even though gastrin is normal. Both PgA and gastrin are raised in renal insufficiency and the Zollinger-Ellison syndrome. A low PgA is indicative of mucosal atrophy and a good indicator for gastric hypoacidity. An additional low PgA:C ratio is indicative of atrophic gastritis or extensive intestinal metaplasia of the stomach. A hypopepsinogenaemia can also be an alarm symptom for gastric cancer. A low PgA and a high gastrin is indicative of corpus atrophy. In primary care, the serological gastric biopsy might be a feasible and appropriate diagnostic method for management of the dyspeptic patient. Further research in general practice has to be done to validate the predictive value of the serological gastric biopsy and to define a diagnostic strategy.
    Scandinavian journal of gastroenterology. Supplement 02/2002;
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    ABSTRACT: No data are available on differences in complication rate and long-term functioning between polyurethane and silicone percutaneous endoscopic gastrostomy (PEG) catheters. 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. 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). Polyurethane PEG catheters were associated with less short-term complications than silicone catheters, but major complications and long-term function were comparable.
    Alimentary Pharmacology & Therapeutics 11/2000; 14(10):1273-7. · 4.55 Impact Factor
  • A C Tan, G D Hartog, C J Mulder
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    ABSTRACT: Many patients are not symptom-free after eradication therapy for Helicobacter pylori and continue to use proton pump inhibitors or H2-receptor antagonists (H2-RAs). To ascertain whether a cohort of patients treated for H. pylori were still taking either proton pump inhibitors or H2-RAs more than 4 years after H. pylori eradication therapy. In 1993-94, a cohort of 167 patients were given eradication therapy for their H. pylori infection. By means of questionnaires to the patient, general practitioner and pharmacist we were able to retrieve data from 151 patients. The use (at the time of questionnaire) of proton pump inhibitors or H2-RAs was noted. Indications for eradication therapy were peptic ulcer disease: 28 patients (19%) or functional dyspepsia: 123 patients (82%). Mean time of follow-up was 1466 +/- 21 days. In this group, 77 patients (51%) still used acid-suppressive medication (proton pump inhibitors 44% and H2-RAs 7%) at the time of the survey (mean follow-up more than 4 years after eradication). In the group treated for peptic ulcer disease (n=28), only nine patients still used proton pump inhibitors or H2-RAs. In contrast, 68 patients who were treated for functional dyspepsia (total number 123) still used proton pump inhibitors or H2-RAs (55%) (P < 0.05). Even after successful H. pylori eradication, < 50% of patients stop acid-suppressive therapy. This contributes significantly to economic cost and raises doubts about the practice of routinely eradicating H. pylori in patients with functional dyspepsia. In contrast, the majority of peptic ulcer patients are able to stop acid-suppressive medication.
    Alimentary Pharmacology & Therapeutics 11/1999; 13(11):1519-22. · 4.55 Impact Factor
  • European Journal of Gastroenterology & Hepatology - EUR J GASTROENTEROL HEPATOL. 01/1999; 11(12).
  • European Journal of Gastroenterology & Hepatology - EUR J GASTROENTEROL HEPATOL. 01/1998; 10(12).
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    ABSTRACT: We investigated whether addition of bismuth subcitrate (BSC, 4 x 120 mg) to a two week therapy scheme of omeprazole (OME, 2 x 40 mg)/amoxicillin (AMO, 4 x 500 mg) increases Helicobacter pylori eradication. Patients with dyspepsia underwent upper endoscopy. H. pylori positive patients were randomized to treatment A (OME/AMO, 83 patients) or treatment B (OME/AMO/BSC, 84 patients). In 65 patients of group A (78%) H. pylori was eradicated as determined from the histological assessment (Sydney classification) of antrum and corpus biopsies. In comparison, in 68 patients of group B (81%) H. pylori was eradicated (p = NS between groups). H. pylori eradication in both groups was associated similarly with a decrease of inflammation and activity whereas atrophy and intestinal metaplasia were not affected. A positive association was revealed between the decrease of H. pylori score and the decrease of both inflammation and activity scores for antrum as well as corpus biopsies. Addition of BSC to OME/AMO does not increase H. pylori eradication in patients with dyspepsia. Eradication of H. pylori is associated with disappearance of epithelial damage (inflammation and activity) in antral and corpus mucosa.
    Helicobacter 01/1998; 2(4):194-8. · 3.51 Impact Factor
  • G den Hartog, C J Mulder, J E Thies, T G Wiersma
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    ABSTRACT: The number of dyspeptic patients with upper abdominal pain that are referred for investigation is increasing and will undoubtedly continue to increase, because these days peptic ulcer disease is increasingly becoming a primary care management issue, the specialist being left to deal with the patients who cannot be helped by antibiotics and antisecretory drugs prescribed by their general practitioner. Many of these patients are referred for an upper endoscopy to rule out organic disease. Carefully taken history, however, shows that a great number of those dyspeptics, on the basis of their clinical manifestations, do have a functional gastrointestinal disorder, representing the 'irritable gut'. A probable better term reflecting the direct relation is the syndrome of 'the constipated stomach'. In our opinion these patients are an important and increasing clinical problem for general practitioners, gastroenterologists, surgeons and physicians. The aim of this article is to make the practitioner aware of advancements in understanding pathophysiologic and psychosocial processes, as well as to give an overview of the great overlap between many functional gastrointestinal disorders, the important role of history-taking and some insights into the functional rectal outlet syndrome.
    Scandinavian journal of gastroenterology. Supplement 01/1998; 225:41-6.
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    ABSTRACT: Background.We investigated whether addition of bismuth subcitrate (BSC, 4 × 120 mg) to a two week therapy scheme of omeprazole (OME, 2 × 40 mg)/amoxicillin (AMO, 4 × 500 mg) increases Helicobacter pylori eradication.Materials and Methods.Patients with dyspepsia underwent upper endoscopy. H. pylori positive patients were randomized to treatment A (OME/AMO, 83 patients) or treatment B (OME/AMO/BSC, 84 patients).Results.In 65 patients of group A (78%) H. pylori was eradicated as determined from the histological assessment (Sydney classification) of antrum and corpus biopsies. In comparison, in 68 patients of group B (81%) H. pylori was eradicated (p = NS between groups). H. pylori eradication in both groups was associated similarly with a decrease of inflammation and activity whereas atrophy and intestinal metaplasia were not affected. A positive association was revealed between the decrease of H. pylori score and the decrease of both inflammation and activity scores for antrum as well as corpus biopsies.Conclusions.Addition of BSC to OME/AMO does not increase H. pylori eradication in patients with dyspepsia. Eradication of H. pylori is associated with disappearance of epithelial damage (inflammation and activity) in antral and corpus mucosa.
    Helicobacter 11/1997; 2(4):194 - 198. · 3.51 Impact Factor
  • P J Wahab, C J Mulder, G den Hartog, J E Thies
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    ABSTRACT: In argon plasma coagulation (APC), high-frequency energy is transmitted to tissue by ionized gas, thus reducing contact with the tissue to a minimum. Successful endoscopic APC was initially reported in the palliative treatment of gastrointestinal neoplasms. The main objectives in this pilot study were to evaluate the treatment indications, efficacy and safety of the use of APC. Between September 1994 and January 1996, APC was used to treat 125 patients with various forms of gastrointestinal pathology. For local palliative treatment, APC was successfully used alongside snare loop coagulation, dilation, stenting and/or radiotherapy to treat the following conditions: carcinoma of the esophagus: 15 patients, mean number of treatment sessions (MTS) 3.3; gastric carcinoma: 10 patients, MTS 4.9; rectosigmoid carcinoma: seven patients, MTS 2.7; carcinoma of the papilla of Vater: two patients, MTS 1.5. Repeated treatment was also effective for tubulovillous adenoma of the rectum (20 patients, MTS 2.5), stomach (three patients, MTS 2.0), duodenum (two patients, MTS 1.5) and papilla of Vater (two patients, MTS 3.0). In addition, APC proved helpful in coagulating the remaining tissue and achieving hemostasis after polypectomy in the colon (18 patients, MTS 1.2) and in endoscopic treatment of Zenker's diverticulum, for coagulation of the tissue bridge and hemostasis (31 patients, MTS 2.5). Finally, APC was helpful in coagulation of multiple gastric polyps (one patient, one session), hemostasis in superficial ulceration of the duodenal bulb (one patient, one session), after dilation of benign stenoses of anastomoses in the esophagus (one patient, one session) and colon (one patient, one session) and for vascular malformations in the colon (three patients, MTS 1.3), duodenum (one patient, one session), antrum (one patient, two sessions), and watermelon stomach (six patients, MTS 2.8). We recognized signs of perforation in six patients after treatment of Zenker's diverticulum (n = 3), polypectomy in the colon (n = 2) and coagulation of angiodysplasia in the cecum. Laparotomy was carried out in two patients; in one, a perforation was sutured, and in the other no focus of leakage was seen. All six patients recovered without further complications. No complications were observed in any other patients. These initial experiences indicate that APC seems to be effective in a number of indications, and relatively safe. Objective evaluation, a longer follow-up period, and comparative trials with other treatment modalities should follow.
    Endoscopy 04/1997; 29(3):176-81. · 5.74 Impact Factor
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    ABSTRACT: Constipation following routine hysterectomy seems to occur more frequently than originally thought. Treatment depends on whether the patient is referred and to whom. Physical examination seems of limited value. Proper protocols for evaluation of complaints after hysterectomy are mandatory. Colonic transit studies and dynamic rectal examination could be useful. We found an overrepresentation of enteroceles in the hysterectomy group. Management of these abnormalities seems much more complicated than was previously thought. Prospective studies are needed to investigate anorectal disorders after hysterectomy.
    Scandinavian journal of gastroenterology. Supplement 02/1997; 223:3-7.
  • C J Mulder, G den Hartog, R J Robijn, J E Thies
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    ABSTRACT: In the past, a number of treatment modalities have been used for the management of a Zenker's diverticulum. These include transcervical diverticulectomy, myotomy, or laser or diathermy treatment via rigid endoscopes. Up to the present, no reports of the treatment of a Zenker's diverticulum with a flexible endoscope have been published. In this study, we present the results of our first 20 patients (13 male; mean age 82 years) prospectively treated with a flexible endoscope applied through diathermy. All patients had significant symptoms such as dysphagia, recurrent aspiration pneumonia and/or weight loss. Treatment using a mean of three sessions per patient was successful, with a good symptomatic response in all subjects. There were no severe complications associated with the therapy. Four patients complained about a sore throat for a few days. During follow-up (mean 6-7 months), three patients died due to unrelated causes, and 17 remained asymptomatic. An important advantage is that it is possible to perform the treatment without general anesthesia, and therefore also in patients whose general health is poor. The technique can easily be performed in an interventional endoscopy unit. Our first experiences show that flexible endoscopic treatment is an effective and relatively safe method.
    Endoscopy 09/1995; 27(6):438-42. · 5.74 Impact Factor