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Biomedical subjects

R W Stockbrügger

Publications and source records attributed to R W Stockbrügger.

At least 19 recordsLinked to original sources
PubMed2006

Toxicity of 6-thioguanine: no hepatotoxicity in a series of IBD patients treated with long-term, low dose 6-thioguanine. Some evidence for dose or metabolite level dependent effects?

BACKGROUND: 6-Thioguanine is used in inflammatory bowel disease since 2001, with promising short-term results. In 2003, liver histology of some 6-thioguanine treated patients showed nodular regenerative hyperplasia. Recently, magnetic resonance imaging revealed nodular regenerative hyperplasia in patients with normal histology. AIMS: Investigating the presence of nodular regenerative hyperplasia in long-term 6-thioguanine treated patients. PATIENTS AND METHODS: Inflammatory bowel disease patients, using 6-thioguanine minimally 24 months, were asked to undergo liver biopsy and magnetic resonance imaging. RESULTS: Fourteen patients used 6-thioguanine minimally 24 months, 13 participated. Mean 6-thioguanine therapy duration, daily dose and 6-thioguanine nucleotide levels were: 36 months, 18.8 mg (0.28 mg/kg) and 705 pmol/8x10(8) erythrocytes, respectively. Liver histology and magnetic resonance imaging showed no nodular regenerative hyperplasia. DISCUSSION: Liver biopsy and magnetic resonance imaging showed no nodular regenerative hyperplasia in these long-term 6-thioguanine treated inflammatory bowel disease patients. 6-thioguanine dose and metabolite levels were lower compared with previous nodular regenerative hyperplasia reports, suggesting dose or metabolite level-dependent effects. Otherwise, nodular regenerative hyperplasia is related with inflammatory bowel disease itself and immunosuppressives, including azathioprine and 6-mercaptopurine. CONCLUSION: 6-Thioguanine is debated due to nodular regenerative hyperplasia. We found no nodular regenerative hyperplasia in inflammatory bowel disease patients with long-term, low dosed 6-thioguanine, suggesting metabolite level-dependent effects. Therefore, 6-thioguanine still seems useful, but in selected patients, intolerant for other immunosuppressives, low dosed and under close surveillance of metabolite levels and hepatotoxity.

Adult↗
PubMed2006

Ulcerative colitis: no rise in mortality in a European-wide population based cohort 10 years after diagnosis.

BACKGROUND: Population based studies have revealed varying mortality for patients with ulcerative colitis but most have described patients from limited geographical areas who were diagnosed before 1990. AIMS: To assess overall mortality in a European cohort of patients with ulcerative colitis, 10 years after diagnosis, and to investigate national ulcerative colitis related mortality across Europe. METHODS: Mortality 10 years after diagnosis was recorded in a prospective European-wide population based cohort of patients with ulcerative colitis diagnosed in 1991-1993 from nine centres in seven European countries. Expected mortality was calculated from the sex, age and country specific mortality in the WHO Mortality Database for 1995-1998. Standardised mortality ratios (SMR) and 95% confidence intervals (CI) were calculated. RESULTS: At follow-up, 661 of 775 patients were alive with a median follow-up duration of 123 months (107-144). A total of 73 deaths (median follow-up time 61 months (1-133)) occurred compared with an expected 67. The overall mortality risk was no higher: SMR 1.09 (95% CI 0.86 to 1.37). Mortality by sex was SMR 0.92 (95% CI 0.65 to 1.26) for males and SMR 1.39 (95% CI 0.97 to 1.93) for females. There was a slightly higher risk in older age groups. For disease specific mortality, a higher SMR was found only for pulmonary disease. Mortality by European region was SMR 1.19 (95% CI 0.91 to 1.53) for the north and SMR 0.82 (95% CI 0.45-1.37) for the south. CONCLUSIONS: Higher mortality was not found in patients with ulcerative colitis 10 years after disease onset. However, a significant rise in SMR for pulmonary disease, and a trend towards an age related rise in SMR, was observed.

Adolescent↗
PubMed2006

The effect of a probiotic drink with Lactobacillus plantarum 299v on the bacterial composition in faeces and mucosal biopsies of rectum and ascending colon.

BACKGROUND: Studies on probiotics mainly base their results on faecal samples, which may not represent the situation in the mucosa of distal and proximal colon. AIM: In a placebo-controlled study, to assess the effect of Lactobacillus plantarum 299v on the bacterial composition of faecal vs. mucosal samples. METHODS: Twenty-nine patients undergoing colonoscopic examination for polyps consumed a twice-daily drink with or without L. plantarum 299v (10(11) CFU/day) for 2 weeks. Faecal samples were collected before and after consumption. During colonoscopy, biopsies were collected from the ascending colon and rectum. The faecal and mucosal bacterial concentrations and prevalence were determined. RESULTS: L. plantarum 299v significantly increased the concentration of faecal lactic acid bacteria, lactobacilli and clostridia, and was identified in two rectal biopsies but not in the ascending colon biopsies of probiotic-treated subjects. Concentrations and prevalence in ascending colon and rectum biopsies were comparable, but were significantly lower compared with faecal samples. CONCLUSIONS: After probiotic consumption, a significant increase in the faecal concentration of lactobacilli was found but concentrations were low in biopsies. The bacterial composition in biopsies of the ascending colon and rectum did not differ based on culture techniques. To further elucidate the modes of action of probiotics, it might be necessary to study differences in colonization with molecular techniques.

Beverages↗
PubMed2005

Phenotype at diagnosis predicts recurrence rates in Crohn's disease.

BACKGROUND: In Crohn's disease (CD), studies associating phenotype at diagnosis and subsequent disease activity are important for patient counselling and health care planning. AIMS: To calculate disease recurrence rates and to correlate these with phenotypic traits at diagnosis. METHODS: A prospectively assembled uniformly diagnosed European population based inception cohort of CD patients was classified according to the Vienna classification for disease phenotype at diagnosis. Surgical and non-surgical recurrence rates throughout a 10 year follow up period were calculated. Multivariate analysis was performed to classify risk factors present at diagnosis for recurrent disease. RESULTS: A total of 358 were classified for phenotype at diagnosis, of whom 262 (73.2%) had a first recurrence and 113 patients (31.6%) a first surgical recurrence during the first 10 years after diagnosis. Patients with upper gastrointestinal disease at diagnosis had an excess risk of recurrence (hazard ratio 1.54 (95% confidence interval (CI) 1.13-2.10)) whereas age >/=40 years at diagnosis was protective (hazard ratio 0.82 (95% CI 0.70-0.97)). Colonic disease was a protective characteristic for resective surgery (hazard ratio 0.38 (95% CI 0.21-0.69)). More frequent resective surgical recurrences were reported from Copenhagen (hazard ratio 3.23 (95% CI 1.32-7.89)). CONCLUSIONS: A mild course of disease in terms of disease recurrence was observed in this European cohort. Phenotype at diagnosis had predictive value for disease recurrence with upper gastrointestinal disease being the most important positive predictor. A phenotypic North-South gradient in CD may be present, illustrated by higher surgery risks in some of the Northern European centres.

Adult↗
PubMed2005

The pharmacokinetic effect of discontinuation of mesalazine on mercaptopurine metabolite levels in inflammatory bowel disease patients.

BACKGROUND: In vitro studies suggest interactions between mesalazine (mesalamine) and thiopurines by thiopurine S-methyltransferase (TPMT) inhibition, influencing the balance of hepatotoxic 6-methylmercaptopurine ribonucleotide and immunosuppressive tioguanine (thioguanine) metabolites. AIM: To examine the in vivo pharmacokinetic interaction between mesalazine and mercaptopurine. METHODS: A prospective study was performed in quiescent inflammatory bowel disease patients using the combination of mercaptopurine and mesalazine. Laboratory parameters, 6-methylmercaptopurine ribonucleotide and tioguanine levels and thiopurine S-methyltransferase activity in erythrocytes were measured at stable medication, after mesalazine discontinuation and mesalazine reintroduction, further mercaptopurine was continued. RESULTS: Seventeen patients were participated. Mean mercaptopurine dose was 0.78 mg/kg/day and median of mesalazine dose was 3000 mg/day. After mesalazine discontinuation, mean tioguanine levels changed significantly from 262 to 209 pmol/8 x 10(8) red blood cell, increasing to 270 after reintroduction. Mean 6-methylmercaptopurine ribonucleotide levels were 1422, 2149 and 1503 pmol/8 x 10(8) red blood cell respectively. Mean 6-methylmercaptopurine ribonucleotide/tioguanine ratio increased significantly from 6.3 at baseline to 11.2. Mean baseline thiopurine S-methyltransferase activity was 0.58 pmol/10(6) red blood cell/h and stable. All patients had wild-type thiopurine S-methyltransferase genotypes however, leucocyte counts were stable. DISCUSSION: A significantly higher tioguanine levels and improving 6-methylmercaptopurine ribonucleotide/tioguanine ratio were found during mesalazine/mercaptopurine combination. Theoretically, mesalazine inhibits thiopurine S-methyltransferase activity. In vivo thiopurine S-methyltransferase activity did not change, however. CONCLUSION: Mesalazine has synergistic effects on mercaptopurine therapy, but the mechanism is unclear. Combining these drugs may be further indication for mesalazine in inflammatory bowel disease treatment.

Adult↗
PubMed2005

Crohn's disease: increased mortality 10 years after diagnosis in a Europe-wide population based cohort.

BACKGROUND: No previous correlation between phenotype at diagnosis of Crohn's disease (CD) and mortality has been performed. We assessed the predictive value of phenotype at diagnosis on overall and disease related mortality in a European cohort of CD patients. METHODS: Overall and disease related mortality were recorded 10 years after diagnosis in a prospectively assembled, uniformly diagnosed European population based inception cohort of 380 CD patients diagnosed between 1991 and 1993. Standardised mortality ratios (SMRs) were calculated for geographic and phenotypic subgroups at diagnosis. RESULTS: Thirty seven deaths were observed in the entire cohort whereas 21.5 deaths were expected (SMR 1.85 (95% CI 1.30-2.55)). Mortality risk was significantly increased in both females (SMR 1.93 (95% CI 1.10-3.14)) and males (SMR 1.79 (95% CI 1.11-2.73)). Patients from northern European centres had a significant overall increased mortality risk (SMR 2.04 (95% CI 1.32-3.01)) whereas a tendency towards increased overall mortality risk was also observed in the south (SMR 1.55 (95% CI 0.80-2.70)). Mortality risk was increased in patients with colonic disease location and with inflammatory disease behaviour at diagnosis. Mortality risk was also increased in the age group above 40 years at diagnosis for both total and CD related causes. Excess mortality was mainly due to gastrointestinal causes that were related to CD. CONCLUSIONS: This European multinational population based study revealed an increased overall mortality risk in CD patients 10 years after diagnosis, and age above 40 years at diagnosis was found to be the sole factor associated with increased mortality risk.

Adolescent↗
PubMed2004

Systematic review: has disease outcome in Crohn's disease changed during the last four decades?

BACKGROUND: Disease outcome in Crohn's disease might have changed during the last four decades. Disease outcome measurement in Crohn's disease has methodological difficulties because of patient selection and lack of proper definition of diagnostic and outcome measurement criteria. AIM: To assess possible changes in disease outcome in Crohn's disease during the last four decades. METHODS: A systematic literature search was performed using the MEDLINE search engine and major international conference libraries. Articles and abstracts were selected according to stringent inclusion criteria. RESULTS: Forty articles and nine abstracts complied with the inclusion criteria. Seven studies with a median follow-up time between 11.1 and 17 years showed standard mortality ratios in Crohn's disease ranging between 2.16 and 0.72 with a tendency of decline during the last four decades. One study with 11.4 years mean follow-up time showed a statistically significant increased relative risk for colorectal cancer that was not confirmed by three others. Sixteen publications applied in the disease recurrence category. Probability of first resective surgery ranged between 38 and 96% during the first 15 years after diagnosis. The overall recurrence and surgical recurrence rates after first resective surgery ranged between 50 and 60, and 28 and 45% respectively during the following 15 years without an apparent time trend. CONCLUSION: This structured literature review provides no hard evidence for change in disease outcome in Crohn's disease during the last four decades.

Crohn Disease↗
PubMed2004

Irritable bowel syndrome in general practice: an overview.

BACKGROUND: Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder that is frequently seen in gastroenterological practice. Population-based studies have shown that at any point in time IBS symptoms are present in about 3%-22% of the general Western population. In general practice, half of all new patients have functional disorders and IBS is responsible for about five consultations per week. General practitioners (GPs) manage the majority of IBS patients, but most knowledge (and research) is based on the smaller percentage of patients managed in secondary care. There is a paucity of literature on differences or similarities between these two groups with regard to clinical characteristics or diagnostic approach. METHODS: The literature published in English about IBS in general practice was reviewed. CONCLUSIONS: Irritable bowel syndrome is frequently encountered in primary care. Primary care IBS patients, compared to secondary care patients, are likely to be young, female and to have less severe symptoms. But this is only true for some symptoms; for example, non-abdominal complaints are equally reported in both groups. The disorder can be diagnosed safely using internationally agreed symptom-based criteria, such as the Rome II criteria. Additional diagnostic measures will be necessary to support the diagnosis in only a minority of situations. Many primary care IBS patients can be managed given adequate reassurance and education, frequently without additional pharmacological treatment.

Health Care Costs↗
PubMed2003

Ratio between serum IL-8 and pepsinogen A/C: a marker for atrophic body gastritis.

BACKGROUND AND AIMS: Elevated serum gastrin and a low pepsinogen A/C ratio are well-recognized markers for atrophic body gastritis (ABG). We have shown that the presence of body atrophy is also associated with elevated serum pro-inflammatory cytokines. This study tested the hypothesis that serum cytokines provide additional information to gastrin and pepsinogens in screening for ABG. METHODS: Two hundred and twenty-six consecutive patients were investigated on referral for upper gastrointestinal endoscopy: 150 were patients with gastro-oesophageal reflux disease, receiving acid inhibitory medication either with proton pump inhibitors (n = 113) or with histamine2-receptor antagonists (n = 37), and 76 were nontreated controls, who had normal endoscopic findings. Gastric mucosal biopsies were sampled for histological examination (Sydney classification). Serum samples were analyzed for gastrin, chromogranin A (CgA), and pepsinogens A and C by RIA, and for the interleukins (IL)-1beta, IL-6, and IL-8 by ELISA. RESULTS: Subjects with ABG had significantly higher serum gastrin (P < 0.01) and serum CgA (P < 0.01) levels and significantly lower pepsinogen A/C ratios (P < 0.001) than those without ABG. Additionally, serum IL-1beta, IL-6 and, especially, IL-8 levels were significantly higher in the subjects with than in those without ABG (P < 0.0001, for all cytokines). To optimize the detection of body atrophy we defined the ABG index: the ratio between the simultaneously measured IL-8 and pepsinogen A/C. The area under the ROC curve for the ABG index was significantly greater than that for serum gastrin and for serum pepsinogen A/C alone (0.91 +/- 0.029 vs. 0.72 +/- 0.042, and vs. 0.83 +/- 0.031, P = 0.018 and P = 0.049). Using the ABG index at a cut-off value of 1.8 pg mL-1, 91% of the cases were classified correctly. CONCLUSIONS: The ratio between serum IL-8 and pepsinogen A/C accurately predicts the presence of ABG. We therefore propose the ABG index as a noninvasive screening test for ABG in population-based studies.

Adult↗
PubMed2003

Screening for colorectal cancer: medical and economic aspects.

BACKGROUND: Colorectal cancer (CRC) is the second commonest cause of cancer death in the Western world. In The Netherlands, CRC causes about 4400 deaths per year, and its diagnosis and treatment make up for a large share of health-care costs. METHODS: Review and discussioN. RESULTS: Experts in the field presently assume that screening for CRC and its precursor lesions, colorectal adenomas (CRAs), could prevent death from colorectal neoplasia by more than 80%. Additionally, there is increasing acknowledgement that CRC screening programmes can save lives at a cost similar to, or even less than, the generally accepted breast cancer or cervical cancer screening programmes. Nonetheless, while neighbouring countries have taken vigorous measures to fight CRC, the Dutch are still hesitating in this matter. This is partly due to some yet unanswered questions concerning the acceptability of screening for CRC in the general population, the starting age and the frequency of screening, the type of screening tests to be used, and the programme organization. In this commentary, general epidemiological and pathogenetic aspects of CRC are addressed. In addition, some frequently asked questions (FAQ) and (very subjective) answers about screening for CRC are offered, as potential substrate for further in-depth discussions. CONCLUSION: The emerging message for the community is that an effective national screening programme is urgently required to reduce the substantial morbidity and mortality from this disease.

Adenoma↗
PubMed2003

Role of alimentation in irritable bowel syndrome.

BACKGROUND: Different food items are made responsible for irritable bowel syndrome (IBS) symptoms, but the physiopathology of IBS remains unclear. AIMS: During a meeting in Nice, France, experts of the European Working Team of the IBiS Club discussed selected data regarding the relationships between alimentation, food items (including fibers) and IBS symptoms. METHODS/RESULTS: Food allergy remains a difficult diagnosis, but medical and general history, presence of general symptoms such as skin rash, and hypersensitivity tests may help in achieving a positive diagnosis. On the other hand, food intolerance is more confusing because of the subjectivity of the relationship between ingestion of certain foods and the appearance of clinical symptoms. Different food items which are commonly implicated in adverse reactions mimicking IBS were found to be stimulants for the gut, suggesting that patients with predominant diarrhea IBS have to be carefully questioned about consumption of different kinds of food (i.e., coffee, alcohol, chewing gum, soft drinks) and not only on lactose ingestion. Gas production is discussed on the basis of retention of intestinal gas as well as on malabsorption of fermentable substrates. The role of a large amount of this kind of substrate reaching the colon is suggested as a potential mechanism of IBS-type symptoms in overeating patients. Regarding the role of fiber in IBS, the expert group concluded that fibers are not inert substances and that they could trigger pain or bloating in some IBS patients. CONCLUSION: Despite numerous reviews on this subject, it is very difficult to give general dietary advice to IBS patients, but dieteticians may have a positive role in managing such patients.

Colon↗
PubMed2002

Effects of anti-tumour necrosis factor-alpha therapy on the quality of life in Crohn's disease.

BACKGROUND: Infusion of anti-tumour necrosis factor-alpha appears to be highly effective in patients with Crohn's disease. AIM: To assess the effect of infliximab on the quality of life in patients with active or fistulizing disease, as measured by the inflammatory bowel disease questionnaire, and to examine the impact on its four dimensions. METHODS: An observational study was conducted in 65 patients. An infusion of 5 mg/kg infliximab was given at week 0 in patients with active disease and at week 0, 2 and 6 in fistulizing disease. Changes from baseline in the total and dimensional inflammatory bowel disease questionnaire scores were calculated and compared between the patient groups. Potential predictors of change in the quality of life were identified. RESULTS: In the active disease group, at week 4, the mean total and dimensional inflammatory bowel disease questionnaire scores improved compared to baseline (P < 0.001). In the fistulizing group, at week 6, all scores changed from baseline (P < 0.05). Improvement in the total inflammatory bowel disease questionnaire score correlated well with the improvement of the Crohn's disease activity index. Systemic and social scores improved more than bowel and emotional scores. Inflammatory Crohn's disease and a young age at diagnosis were predictors for a better response to infliximab therapy. CONCLUSIONS: Infliximab therapy improves all dimensions of the quality of life in patients with Crohn's disease.

Adult↗
PubMed2002

Discordance between the degree of osteopenia and the prevalence of spontaneous vertebral fractures in Crohn's disease.

BACKGROUND: A high prevalence of osteoporosis has been noted in Crohn's disease, but data about fractures are scarce. METHODS: The relationship between low bone mineral density and the prevalence of vertebral fractures was studied in 271 patients with ileo-caecal Crohn's disease in a large European/Israeli study. One hundred and eighty-one currently steroid-free patients with active Crohn's disease (98 completely steroid-naive) and 90 steroid-dependent patients with inactive or quiescent Crohn's disease were investigated by dual X-ray absorptiometry scan of the lumbar spine, a standardized posterior/anterior and lateral X-ray of the thoracic and lumbar spine, and an assessment of potential risk factors for osteoporosis. RESULTS: Thirty-nine asymptomatic fractures were seen in 25 of 179 steroid-free patients (14.0%; 27 wedge, 12 concavity), and 17 fractures were seen in 13 of 89 steroid-dependent patients (14.6%; 14 wedge, three concavity). The prevalence of fractures in steroid-naive patients was 12.4%. The average bone mineral density, expressed as the T-score, of patients with fractures was not significantly different from that of those without fractures (-0.759 vs. -0.837; P=0.73); 55% of patients with fractures had a normal T-score. The bone mineral density was negatively correlated with lifetime steroids, but not with previous bowel resection or current disease activity. The fracture rate was not correlated with the bone mineral density (P=0.73) or lifetime steroid dose (P=0.83); in women, but not in men, the fracture rate was correlated with age (P=0.009). CONCLUSIONS: The lack of correlation between the prevalence of fractures on the one hand and the bone mineral density and lifetime steroid dose on the other necessitates new hypotheses for the pathogenesis of the former.

Absorptiometry, Photon↗
PubMed2002

The rectum: a window to irritable bowel syndrome?

This report summarizes current concepts and information gathered to date about the rectum in the irritable bowel syndrome (IBS) that were presented at the 10th meeting of IBiS Club held in Leuven, Belgium. A working group of experts in the field of IBS discussed whether the rectum or the whole colon is the better site to test in IBS patients and provided suggestions for a number of areas where further advances are required.

Biopsy↗
PubMed2002

Pneumatosis cystoides intestinalis, four cases of a rare disease.

Pneumatosis cystoides intestinalis (PCI) is a disease in which small gas-filled cysts appear in the intestinal wall. Four cases presented here demonstrate the diversity of the associated diseases. In two of the patients constipation probably played a role; in the third patient decreased colonic motility, elevated intestinal pressure and increased mucosal permeability in the context of enteritis treated with codeine was the underlying problem; in the fourth high protein feeding and bowel ischaemia was diagnosed. Various aetiologies are presented in the literature. There is no specific history and physical or laboratory findings do not help to diagnose PCI. Plain abdominal film, ultrasound, computer tomography, magnetic resonance imaging, barium contrast studies and/or endoscopy may be necessary for diagnosis. Therapy is based on enhancing partial oxygen pressure in the bowel wall. PCI usually runs a benign course.

Adult↗
PubMed2002

Liver enzyme elevation induced by hyperemesis gravidarum: aetiology, diagnosis and treatment.

Three primigravidae were admitted during the first trimester of pregnancy with nausea, vomiting, ketonuria and liver enzyme elevation of varying severity. A 29-year-old woman had elevated aminotransferase values, at levels described in the literature (ASAT 112 U/l, ALAT 214 U/l). The second patient, a woman aged 26 years, had undergone in vitro fertilisation and showed higher liver enzyme elevation, including the total bilirubin level (ASAT 250 U/l, ALAT 474 U/l, total bilirubin 59.8 micromol/l). A 30-year-old woman had extremely high aminotransferase values (ASAT 705 U/l, ALAT 1674 U/l) and she is the first reported patient with ALAT values exceeding 1,000 U/l in connection with hyperemesis gravidarum. Gallstone disease, viral and drug-induced hepatitis were excluded in all of these patients. Treatment was symptomatic and the abnormal liver tests returned to normal promptly when the vomiting resolved, independent of the severity of liver enzyme elevation. The pregnancies proceeded normally and all three patients delivered healthy babies.

Adult↗
PubMed2001

[Epidemiological developments and insights in chronic inflammatory bowel diseases].

In the Western world, a sharp increase in the incidence of both Crohn's disease and ulcerative colitis was observed during the sixties and seventies, after which it reached a plateau at around 7 and 12 new cases per 100,000 inhabitants per year, respectively. Both chronic inflammatory bowel diseases usually commence between 15 and 30 years of age. Most patients have a normal life expectancy. A multifactorial model has been proposed to explain the pathogenesis, in which there seems to be an interaction between genetic predisposition, environmental factors and an altered immune response (occurring either after or because of the disease). Smoking is a clear risk factor in the development of Crohn's disease and it also negatively influences the clinical outcome. On the other hand, stopping smoking is a risk factor in the development of ulcerative colitis.

Adolescent↗