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Biomedical subjects

C J Mulder

Publications and source records attributed to C J Mulder.

At least 19 recordsLinked to original sources
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↗
PubMed1999

High prevalence of celiac disease in apparently healthy blood donors suggests a high prevalence of undiagnosed celiac disease in the Dutch population.

BACKGROUND: In the last few years the prevalence of celiac disease (CD) seems to have increased. It is clear that subclinical and silent CD exist in a large subgroup of the celiac population. METHODS: The aim of this study was to evaluate the prevalence of CD in an apparently healthy population. Blood samples were obtained from 1000 apparently healthy blood donors at Arnhem and Nijmegen Blood Donation Centers from January 1997 through April 1998. Sera from 660 blood donors were assayed for total IgA. By means of immunofluorescence, antibodies, including those to endomysium (EMA), were determined. Serum immunoglobulin levels (IgA) were assayed by means of nephelometry. All donors who had positive serology for EMA underwent small-intestinal biopsy. RESULTS: Of the 1000 healthy blood donors 3 had positive EMA. Small-intestinal biopsy of two of these showed subtotal villous atrophy (Marsh IIIb), and the third had intraepithelial lymphocytosis and crypt hyperplasia (Marsh II). The prevalence of gluten sensitivity was 1 of 330. Low IgA (0.60-0.23 g/l) in our study group was found in 9 of 660 (1%), but no one showed an IgA < or = 0.02 g/l. CONCLUSION: Our study shows that the prevalence of gluten-sensitivity in apparently healthy blood donors is 3 of 1000, which suggests a high prevalence of CD in the Dutch population, in contrast to the results of the last published Dutch epidemiologic studies. The recorded prevalence will increase further with greater recognition of subclinical and asymptomatic forms detected by screening tests.

Adult↗
PubMed1999

The relationship between anti-endomysium antibodies and villous atrophy in coeliac disease using both monkey and human substrate.

BACKGROUND/OBJECTIVE: Circulating antibodies offer a noninvasive diagnostic screening test in patients with coeliac disease with severe histopathological abnormalities. This study assesses for the first time the sensitivity and reliability of anti-endomysium in screening for coeliac disease in patients with milder forms of villous atrophy using human umbilical cord and monkey ileum. MATERIALS AND METHODS: Serum from 124 adults and children > 2 years old including 33 patients with coeliac disease on a gluten-free diet and 91 patients referred to the laboratory for screening was studied. The presence of IgA-anti-gliadin (AGA) (ELISA) and IgA-anti-endomysium (EMA) was detected in the serum using monkey ileum and human umbilical cord (HUC) substrates. Patients with abnormal serology results or severe clinical complaints were invited to attend for a small-bowel biopsy. The prevalence of EMA detected on monkey ileum and HUC was compared with the histopathological features of coeliac disease at presentation. Fifty-three of the 91 patients screened for coeliac disease underwent a small intestinal biopsy. RESULTS: Twenty-three of the 91 patients suspected of having coeliac disease had coeliac disease. The EMA test was positive in 18 of 23 using both monkey ileum and HUC (sensitivity 78%). Partial villous atrophy (PVA) was seen in four of the five EMA-negative patients, and subtotal/total villous atrophy (SVA/TVA) was demonstrated in 18 of the 23 cases with positive EMA. Both substrates detected identical positive cases. There was an excellent concordance between EMA sensitivity evaluated on HUC and those on monkey ileum. One patient was EMA-negative on monkey ileum but positive on HUC and one patient who was EMA-positive on monkey ileum was EMA-negative on HUC. Only one of 33 coeliac disease patients on gluten-free diet for more than one year with persisting TVA had positive EMA. The rest of the cases had a negative EMA on both HUC and monkey ileum. CONCLUSION: A negative result for EMA in coeliac disease patients with a normal IgA value does not exclude the diagnosis of coeliac disease. A positive EMA is seen mostly in those coeliac disease patients with severe tissue damage (SVA/TVA). EMA has a low sensitivity in coeliac disease patients with PVA in spite of use of different substrates.

Adult↗
PubMed1999

Increased survival in advanced primary biliary cirrhosis patients with regular albumin infusions?

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease. Frequently, it can slowly progress to cirrhosis and, finally, death. Liver transplantation is the only way to avoid this endpoint. For patients not accepted for liver transplantation, only symptomatic treatment remains. In advanced PBC, one of the main concerns is a decreasing albumin level. As albumin is an important protein in the human body, we wondered whether regular albumin infusions may result in a higher quality of life and prolong survival. In this case report we describe three patients who survived for a remarkably long time on this treatment regimen before finally succumbing to the sequela of advanced liver disease. Some features of albumin are mentioned which may help explain this phenomenon. We conclude that regular albumin infusions may be a means of decreasing morbidity and prolonging survival in a subgroup of patients with advanced PBC. However, prospective evaluation of regular albumin infusions in a group of PBC patients (e.g. those rejected for liver transplantation) seems mandatory.

Aged↗
PubMed1999

Sensitivity of antiendomysium and antigliadin antibodies in untreated celiac disease: disappointing in clinical practice.

OBJECTIVE: We have undertaken a study to assess the efficiency of serological tests in the diagnosis of celiac disease (CD) during the period January 1, 1994 to January 7, 1997. Our aim was to evaluate the sensitivity of IgA antiendomysium (EMA) and IgA antigliadin (AGA) with regard to the degree of histological abnormality in biopsy specimens of small intestine in untreated celiac disease patients and first-degree relatives. METHODS: The study population comprised 101 cases: 85 untreated celiac patients and 16 first-degree relatives with a mean age of 42 yr (range, 2-76 yrs). Sixteen of 85 were excluded from study because they did not satisfy the study or diagnostic criteria of CD. EMA and AGA have been compared with the degree of villous atrophy (VA) in 69 celiac patients and 16 relatives according to the Marsh criteria of 1992. We divided the Marsh III histology into three subgroups as follows: Marsh IIIa (partial VA), Marsh IIIb (subtotal VA), and Marsh IIIc (total villous atrophy). RESULTS: The specificity and positive predictive value of EMA for CD was excellent, because all EMA-positive patients (n = 42) were diagnosed with CD. The sensitivity of EMA, however, differed between CD subgroups; in patients with total VA, the sensitivity of EMA was 100% (17/17). However, in patients with partial VA (Marsh IIIa), the sensitivity of EMA was disappointing, only 9/29 (31%). Three of 72 celiacs with Marsh IIIb and Marsh IIIc had IgA deficiency and were excluded from the study. Elevated AGA has been detected in the sera of 39 of 69 (62%) patients. A combination of EMA and AGA tests showed a sensitivity of 76% (53/69). None of 16 first-degree relatives with Marsh I-II had positive EMA. CONCLUSIONS: Interpretation of negative serology needs great awareness. Although EMA sensitivity in total villous atrophy is excellent, in partial villous atrophy the sensitivity of EMA appears to be disappointing. Our experience shows that EMA and AGA have only limited value in screening programs for CD.

Adult↗
PubMed1999

Zapping Zenker's diverticulum: gastroscopic treatment.

Zenker's diverticulum (ZD) is a common cause of dysphagia in the elderly. Many symptomatic elderly are poor candidates for surgery and/or ear, nose and throat treatment. The author's first experiences with gastroscopic treatment by cutting the Zenker bridge to allow an overflow have recently been published. Only patients with contraindications for general anesthesia were accepted to the pilot group. However, the author now treats all ZD patients in this manner. One hundred and twenty-five patients (male to female ratio 1. 6) were referred for treatment from 1993 to 1997. After introduction of the gastroscope into the esophagus, a nasogastric tube was positioned to treat a ZD bridge with a height of less than 1 cm. The ZD bridge was divided by argon plasma coagulation, if necessary, in combination with monopolar forceps, Savary dilator and/or precut needle. All patients received antibiotics, topical anesthesia to the throat, if necessary, and intravenous midazolam, if possible. Radiography was performed after treatment. Normalization of the diet was allowed when the x-ray showed no signs of leakage. All patients referred for treatment were treated successfully. The median age was 77 years (range 41 to 100 years). Symptomatic improvement was seen in all patients after treatment. Complications included subcutaneous emphysema (n=17), mediastinal emphysema (n=5) and bleeding (n=2). One patient (95 years of age) died in her nursing home 27 days after treatment due to massive pulmonary embolism. The thirty-day mortality rate was otherwise zero. Three patients had been previously treated by surgeons and 12 by ear, nose and throat physicians, without sufficient improvement; all were adequately treated by the author. The mean number of treatment sessions was 1.8. This approach seems safe and effective. Treatment of every patient was possible and was carried out, even in patients in very poor condition, without general anesthesia.

Adult↗
PubMed1999

Contribution of the MHC region to the familial risk of coeliac disease.

Susceptibility to coeliac disease is genetically determined by possession of specific HLA-DQ alleles, acting in concert with one or more non-HLA linked genes. The pattern of risk seen in sibs and twins in coeliac disease is most parsimonious with a multiplicative model for the interaction between the two classes of genes. Based on a sib recurrence risk for coeliac disease of 10% and a population prevalence of 0.0033, the sib relative risk is 30. To evaluate the contribution of the MHC region to the familial risk of coeliac disease, we have examined haplotype sharing probabilities across this region in 55 coeliac disease families. Based on these probabilities the sib relative risk of coeliac disease associated with the MHC region is 3.7. Combining these results with published data on allele sharing at HLA, the estimated sib relative risk associated with the MHC region is 3.3. Therefore, the MHC genes contribute no more than 40% of the sib familial risk of coeliac disease and the non-HLA linked gene (or genes) are likely to be the stronger determinant of coeliac disease susceptibility.

Celiac Disease↗
PubMed1998

SAT and serology in adult coeliacs, seronegative coeliac disease seems a reality.

UNLABELLED: The aim of this study was to assess the correlation of sugar absorption test (SAT) using Lactulose/Mannitol/Sucrose (LMS), with IgA-endomysium (EMA), and IgA-gliadin (AGA) antibodies in relation to the severity of the intestinal mucosal damage in adult coeliacs. We have differentiated the Marsh classification in partial villous atrophy (VA) (III a), subtotal VA (III b), and total VA (III c). Twenty-nine untreated adults coeliacs, with a mean age of 47 years, range 20-76 yrs were studied over 3 years. SAT, IgA-AGA and IgA EMA were performed in 29 consecutive coeliac patients with villous atrophy on a gluten containing diets. RESULTS: Histopathological evaluation of small intestinal mucosa showed a partial VA in 14/29, subtotal VA in 10/29 and total VA in 5/29. All coeliacs with total VA had positive EMA (5/5 100%). However in coeliacs with partial VA sensitivity of EMA was poor (4/14 29%). Sensitivity of EMA in patients with subtotal VA was 50% (5/10). AGA was raised in 3/14 (21%), 6/10 (60%), and in 4/5 (80%) coeliacs with partial, subtotal and total VA respectively. AGA was raised in 13/29 (sensitivity 45%). SAT was abnormal in 26/29 (sensitivity: 89%). One patient had abnormal SAT, EMA and AGA. Eleven of 29 patients (38%) were negative for AGA and EMA, but SAT was abnormal in 10 of them. One patient was positive for EMA, negative for AGA, normal for SAT. EMA and/or AGA were positive in 18/29 (sensitivity 62%). Our study suggests that negative predictive value of serology should be interpreted cautiously since coeliacs with partial VA are negative in serology. Over the last ten years SAT and EMA have been accepted as screening tools for CD. SAT seems to be more sensitive than serology. However there is no standardized agreement in the literature for serology and SAT. A combination of SAT and serology may provide a good sensitivity in order to detect that subgroup of coeliacs with milder histopathological abnormality.

Adult↗
PubMed1998

The constipated stomach. An underdiagnosed problem in patients with abdominal pain?

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.

Abdominal Pain↗
PubMed1998

Drug therapy: dose-response relationship of oral mesalazine in inflammatory bowel disease.

Mesalazine is widely used in the treatment of inflammatory bowel disease. Little is known about the dose-response relationship and about possible dose related side effects. In ulcerative colitis higher dosages of mesalazine (3 g) are more effective in maintaining a remission than lower dosages (1.5 g). In mild to moderately active ulcerative colitis, studies also indicate that higher dosages might be more effective in inducing remission. Dose-comparing studies in Crohn's disease are even more sparse, but the available results indicate higher efficacy at higher dose levels. None of the known side effects of mesalazine are clearly dose-related. A pH-dependent release system, however, can cause a sudden release of high doses of mesalazine. Consequent peak levels in serum have been implicated in mesalazine induced nephrotoxicity. In conclusion, despite the current practice of using increasing dosages of mesalazine in inflammatory bowel disease, both efficacy and safety have been established tentatively.

Administration, Oral↗
PubMed1998

Optimal treatment of Helicobacter pylori with ranitidine bismuth citrate (RBC): a randomized comparison between two 7-day triple therapies and a 14-day dual therapy.

OBJECTIVE: We investigated two promising 1-wk RBC-triple therapies in comparison to the already well investigated 2-wk RBC dual therapy. METHODS: We conducted two randomized, open, parallel group studies in 13 hospitals in the Netherlands. H. pylori-positive patients without active ulceration were randomized to 14-day RBC 400 mg b.i.d. plus clarithromycin 500 mg b.i.d. (n = 56) or to either 7-day RBC 400 mg b.i.d. plus tetracycline 500 mg q.i.d. plus metronidazole 500 mg t.i.d. (n = 63) in study 1, or to 7-day RBC 400 mg b.i.d. plus amoxycillin 1000 mg b.i.d. plus clarithromycin 500 mg b.i.d. (n = 49) in study 2. At least 6 wk later patients were reendoscoped with antral and corpus biopsies for CLOtest, culture, and histology, and cure was assumed if all tests were negative. RESULTS: Results from the studies were pooled. All regimens were well tolerated with only 1 drop-out because of side effects. Cure rates per protocol/intention to treat were 96%/95% for RBC-CLA dual therapy, 89%/86% for RBC-TET-MET triple therapy, and 93%/92% for RBC-AMO-CLA triple therapy. From 126 patients, a pretreatment antibiogram was available. Metronidazole resistance did not affect the performance of RBC-CLA or RBC-AMO-CLA. In the RBC-TET-MET group, 97% (32/33) with a metronidazole sensitive strain were cured vs 57% (four of seven) with a resistant strain. Of three patients with a pretreatment clarithromycin resistant strain; one failed RBC-CLA dual therapy and two failed RBC-AMO-CLA triple therapy. CONCLUSIONS: All regimens were well tolerated and achieved comparable and very high cure rates. Statistical or clinical relevant differences were not detected. All three regimens can be used as initial anti-Helicobacter therapy and can compete with 7-day PPI-triple therapies. More data are needed on the influence of antimicrobial resistance on the performance of individual triple therapies. The local prevalence of antimicrobial resistance will determine which regimen should be chosen for a certain geographical area.

Adult↗
PubMed1997

[Chronic hepatitis C in hemodialysis patients].

Hepatitis C virus (HCV) is an important cause of chronic hepatitis in dialysis patients. With regard to epidemiology, the time on haemodialysis, the (previous) use of intravenous drugs as well as the number of blood transfusions received are important risk factors. There are strong indications suggesting nosocomial transmission of HCV. Strict application of infection prevention procedures in haemodialysis units is mandatory to restrain spread of HCV infection. Preliminary results show equal efficacy of alpha-interferon in normalisation of serum transaminases in dialysis patients and in patients with normal kidney function. However, in both groups relapses occur often, despite induction of remission. Antiviral therapy (with interferon and ribavirin) is emerging as a valid option to induce HCV eradication in dialysis patients. Thereafter, transplantation may be considered.

Antiviral Agents↗
PubMed1997

[Gluten as food additive in The Netherlands: cheese forbidden for celiac patients?].

A new coating for cheese, to be introduced in May, consists entirely of natural degradable components. The coating is based on wheat gluten. This increase in the amount of gluten in the Dutch diet may lead to overt coeliac disease in people with a subclinical form of it, and will limit the dietary choices of patients already suffering from the disease.

Celiac Disease↗