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Biomedical subjects

J Fallingborg

Publications and source records attributed to J Fallingborg.

At least 19 recordsLinked to original sources
PubMed2004

Randomized controlled azathioprine withdrawal after more than two years treatment in Crohn's disease: increased relapse rate the following year.

INTRODUCTION: Azathioprine is effective for maintenance of remission in Crohn's disease, however, duration of efficacy and the dose response relationship has not been fully evaluated. AIMS: To investigate whether patients kept in remission by azathioprine treatment for >2 years benefit from further treatment, and to explore dose-response relationship. PATIENTS AND METHODS: In an open 12-month trial, patients with inactive Crohn's disease after >2 years (median 37 months) of azathioprine treatment were randomized to azathioprine withdrawal or continued treatment. Primary end point was relapse defined as: (i) Crohn's disease activity index rise >/= 75, and Crohn's disease activity index >150 or (ii) disease activity requiring intervention. RESULTS: Of 29 patients, 28 completed the observation period or relapsed. Eleven of 13 patients (85%) continuing azathioprine remained in remission compared with seven of 15 (47%) observed without azathioprine (P = 0.043). In patients who had been treated with azathioprine >1.60 mg/kg/day the difference was even more pronounced, eight of nine (89%) vs. four of 12 (33%) respectively (P = 0.017). CONCLUSIONS: Patients with Crohn's disease in remission after >2 years of continuous azathioprine treatment will benefit from further continued treatment. Further controlled studies with azathioprine doses <2.0 mg/kg/day are needed.

Adult↗
PubMed2003

Budesonide treatment of collagenous colitis: a randomised, double blind, placebo controlled trial with morphometric analysis.

BACKGROUND: Collagenous colitis is characterised by diarrhoea, lymphocytic inflammation, and a thickened subepithelial collagen layer in the colorectal mucosa. No standard treatment of the disease is established. AIMS: To investigate the clinical and histological effect of oral budesonide (Entocort, AstraZeneca) in the treatment of collagenous colitis. PATIENTS: Twenty patients with collagenous colitis (collagen layer >10 micro m) and diarrhoea (>4 stools/day and/or stool weight >200 g/day). METHODS: A randomised, double blind, placebo controlled trial of budesonide treatment. Patients were randomised to placebo or budesonide for eight weeks. Stool frequency and stool weight were registered before and after treatment. Sigmoidoscopy was performed before and after treatment, and biopsies at fixed locations were obtained for morphometric analysis. RESULTS: Ten patients were randomised to budesonide and 10 to placebo. All 10 patients receiving budesonide had a clinical response compared with two in the placebo group (p<0.001). In the budesonide group, stool weight was reduced from 574 g/day to 200 g/day and stool frequency was reduced from 6.2/day to 1.9/day (p<0.01). The histological inflammation grade in the sigmoid mucosa and the thickness of the collagen layer were significantly reduced. A correlation between the grade of inflammation as well as collagen layer thickness and stool weight was found. No side effects were reported. Eight of 10 patients had relapse of symptoms within eight weeks after stopping treatment. CONCLUSIONS: Budesonide is a highly effective and well tolerated treatment of collagenous colitis. There is a high risk of relapse after stopping eight weeks of treatment.

Adult↗
PubMed1999

Intraluminal pH of the human gastrointestinal tract.

After a short introduction (chapter 1) methods of measuring gastrointestinal pH are described in chapter 2. The methods are divided into intubation techniques and tubeless methods, and the advantages and disadvantages are discussed. Measurements with pH-sensitive, radiotransmitting capsules are highlighted, and methodological problems with these capsules are described. Chapter 3 concerns the gastrointestinal pH profile of healthy subjects. The intraluminal pH is rapidly changed from highly acid in the stomach to about pH 6 in the duodenum. The pH gradually increases in the small intestine from pH 6 to about pH 7.4 in the terminal ileum. The pH drops to 5.7 in the caecum, but again gradually increases, reaching pH 6.7 in the rectum. The physiological background of these pH values is discussed. Chapter 4 describes the effect of gastrointestinal pH on bacterial flora, absorption of vitamins and electrolytes, and on the activity of digestive enzymes. The pH-profile in children is described in chapter 5. The profile is identical with that of adults, and it is therefore concluded that the release of a drug from pH-dependent, controlled-release preparations is also probably identical with that of adults. Chapter 6 describes the correlation between certain diseases and the gastrointestinal pH. A resection of the colon and the creation of an ileostomy do not affect the pH of the remaining gut. An ileocaecal resection shortens the small intestinal transit time, increases pH of the proximal colon, but does not change the pH-profile of the small intestine. Chronic pancreatitis and cystic fibrosis seem to decrease pH of the proximal small intestine. Very low colonic pH values have been observed in severe active ulcerative colitis and in Crohn's disease, but the background and clinical implication of this phenomenon are not clear. Chapter 7 describes the modulating effect of diet and drugs on gastrointestinal pH. Diet primarily has an effect on the colonic pH, whereas drugs might affect both small intestinal and colonic pH. The different effects are described. Finally, chapter 8 summarizes the present knowledge about gastrointestinal pH, and future investigations are proposed.

Digestive System Physiological Phenomena↗
PubMed1998

Small intestinal transit time and intraluminal pH in ileocecal resected patients with Crohn's disease.

The pH and transit times of the gut are important for the delivery of active drug from several tablets used in the treatment of Crohn's disease (CD). Many patients with CD undergo an ileocecal resection, which might influence small intestinal pH and transit time. The effect of ileocecal resection on these variables has not previously been studied. Intraluminal pH and transit time were measured in nine ileocecal-resected CD patients and 13 healthy volunteers using pH-sensitive radiocapsules. Small intestinal transit time (SITT) was significantly shorter in ileocecal-resected patients (5.2 hr, controls 8.0 hr). The pH levels of the small intestine were identical in patients and controls, whereas cecal pH was 0.9 pH units higher in resected CD patients. The time spent with pH higher than 5.5, 6.0, 6.5, and 7.0 was significantly shorter in patients than in controls. There was no correlation between the SITT and the length of resected ileum or between the SITT and the time elapsed since the resection. We conclude that ileocecal resection decreases the SITT and the time with pH higher than 5.5-7.0. The study indicates that this reduction of the SITT is mainly due to the resection of the ileocecal valve and is, to a certain extent, independent of the length of resected ileum. An ileocecal resection might therefore affect the delivery of active drug from tablets with pH-dependent delivery.

Adult↗
PubMed1994

Comparative bioavailability of 5-aminosalicylic acid from a controlled release preparation and an azo-bond preparation.

BACKGROUND: Knowledge of the bioavailability of 5-aminosalicylic acid (5-ASA, mesalazine) from the different 5-ASA-containing drugs is important for rational therapy of inflammatory bowel diseases. METHODS: The local and systemic bioavailability of 5-ASA from a controlled release 5-ASA preparation (Pentasa--2, 4 or 6 g/day) was investigated and compared with the azo-bond 5-ASA preparation olsalazine (Dipentum--2 g/day) in 13 healthy volunteers during steady state conditions. RESULTS: The therapeutically relevant parameter of 5-ASA at the rectal level, expressed as the mean concentration in faecal water, showed a significant trend towards higher concentrations with increasing Pentasa dose: 9.2 mmol/L, 19.0 mmol/L and 24.4 mmol/L, respectively. The concentration of olsalazine 2 g/day was 16.0 mmol/L. The concentration of the metabolite N-acetyl-5-aminosalicylic acid (Ac-5-ASA) did not rise with increasing Pentasa dose, indicating saturable presystemic acetylating capacity of 5-ASA. Total urinary excretion of 5-ASA and Ac-5-ASA, as a percentage of the daily ingested 5-ASA dose, remained constant on the three Pentasa doses, but there was a significant increase in the 5-ASA fraction. Mean steady state plasma concentrations of 5-ASA and Ac-5-ASA were significantly higher on Pentasa 4 g/day and 6 g/day than on 2 g/day. Values on Pentasa 2 g/day were comparable with those on olsalazine 2 g/day. CONCLUSIONS: The study confirmed that 5-ASA is released from Pentasa in a predictable manner, the amount released increasing with dose. Olsalazine is an excellent generator of 5-ASA in the colon.

Administration, Oral↗
PubMed1994

Effect of olsalazine and mesalazine on intraluminal pH of the duodenum and proximal jejunum in healthy humans.

BACKGROUND: Treatment of inflammatory bowel disease with olsalazine causes diarrhoea in 10% of patients. This is claimed to be caused by a drug effect on mucosal transport in the small intestine, which might be reflected in the intraluminal pH. We aimed to study the effect on jejunal pH of olsalazine (Dipentum) and an alternative preparation, slow-release mesalazine (Pentasa). METHODS: Thirteen healthy volunteers, seven male and six female, participated in a randomized, crossover study. Steady-state conditions were obtained after ingestion of 2 g or 6 g mesalazine daily or 2 g olsalazine daily for 1 week. The pH of the duodenum and proximal jejunum was measured by using pH-sensitive, radiotransmitting capsules, the location of which was confirmed by fluoroscopy. RESULTS: No effect of either drug on duodenal pH was detected. Mean duodenal pH ranged from 6.18 to 6.22. The mean pH of the pre-medication proximal jejunum was 6.02. Mesalazine had no significant effect, but olsalazine significantly increased the pH of the proximal jejunum (mean pH, 6.47). CONCLUSIONS: Our results indicate that the effect of olsalazine on jejunal transport of electrolytes and water, observed in experimental studies, also applies to human subjects in steady-state conditions, and adaptation does not occur within 6 days.

Adolescent↗
PubMed1993

Bioavailability of 5-aminosalicyclic acid from slow release 5-aminosalicyclic acid drug and sulfasalazine in normal children.

The bioavailability of a controlled release 5-aminosalicyclic acid preparation (Pentasa) was investigated in nine healthy children after a medication period of six days (1000 mg/day) and compared with sulfasalazine (Salazopyrin) (2000 mg/day). The local bioavailability in the distal gut lumen, reflected by the 5-aminosalicylic acid concentration in the fecal water, showed comparable values after Pentasa (4.44 mmol/liter) and Salazopyrin (6.25 mmol/liter). The concentration of N-acetyl-5-ASA was significantly higher after Pentasa, reflecting the more proximal release of 5-aminosalicyclic acid compared with Salazopyrin. No relation was found between the 5-aminosalicylic acid fecal water concentration water concentration and the 5-aminosalicylic acid dose per kilogram of body weight. The urinary excretion of 5-aminosalicylic acid and N-acetyl-5-aminosalicylic acid was higher after Pentasa than after Salazopyrin (32% vs 25%). Dose interval plasma concentration curves showed low values after both preparations. Based on the concept that the fecal water concentration is decisive for the efficacy of 5-aminosalicylic acid in distal inflammatory bowel disease, Pentasa treatment offers a relevant alternative in cases of Salazopyrin intolerance or allergy in children. The higher systemic bioavailability from Pentasa warrants monitoring of the renal function.

Aminosalicylic Acids↗
PubMed1993

Very low intraluminal colonic pH in patients with active ulcerative colitis.

Intraluminal gastrointestinal pH was measured in seven patients with active ulcerative colitis (four male, three female). A radiotelemetry capsule was used, and its location was determined by fluoroscopy. Satisfactory measurements were obtained from six, in all of whom pH levels were normal in the stomach and small intestine. Three patients also had normal pH values in the colon. However, in the remaining three patients very low pH levels (lowest values 2.3, 2.9, and 3.4) were found in the proximal parts of the colon. Five of the seven patients, including the three with low pH in the colon, underwent colectomy. The mechanism behind the low intraluminal pH in some patients with ulcerative colitis is speculative. Increased fecal concentrations of lactate occur in active disease, but some of the pH values measured in our study were below the pKa value of lactate. The study demonstrates that very low intraluminal pH levels in the colon occur in some patients with active ulcerative colitis. This might be an indicator of severe activity of the disease.

Adult↗
PubMed1992

Frequency of Helicobacter pylori and gastritis in healthy subjects without gastrointestinal symptoms.

To investigate the frequency of Helicobacter pylori and gastritis in asymptomatic adults, 30 healthy volunteers underwent upper endoscopy. Biopsy specimens were obtained from the corporeal and antral mucosa of the stomach. The specimens were examined by light microscopy for gastritis and the occurrence of H. pylori. In 12 subjects signs of gastritis were noted at endoscopy, but only in 7 of them was this diagnosis confirmed histologically. No other abnormalities were observed by the endoscopist. Histologic examination was normal in 17 subjects, but in 13 subjects (43%) inflammation was found in the gastric specimens. Ten had inflammation both in the corpus and in the prepyloric specimens, and in six of these subjects H. pylori was discovered. H. pylori was only found in subjects with inflammation in both the corpus and the antrum. Subjects with gastritis were slightly older than subjects with normal gastric mucosa (median age, 47 versus 37 years; not significant). In the group of subjects with gastritis, persons with H. pylori were older than those without (median age, 53.5 versus 36 years; p = 0.05). The results of our study indicate that gastritis is present before colonization with H. pylori occurs. This could imply that H. pylori is not the cause of gastritis but that the presence of gastritis is a prerequisite for colonization of the bacterium in the stomach.

Adult↗
PubMed1992

Primary sclerosing cholangitis in patients with ulcerative colitis.

The prevalence of primary sclerosing cholangitis (PSC) in patients with ulcerative colitis (UC) attending the Depts. of Medical and Surgical Gastroenterology, Aalborg Hospital, during a 12-year period, was determined. All patients with an alkaline phosphatase (ALP) value above the normal range were investigated. Of 305 patients with UC, 24 patients had elevated ALP values, and 11 of these (3.6% of the study population), 4 males and 7 females, were found to have PSC by direct cholangiography. In five patients the disease worsened (two patients died of cholangiocarcinoma), in four it was stationary, and in two patients the disease improved during a mean observation period of 6 years. No differences in location of disease, disease activity, or duration of disease were found between patients with UC and PSC and patients with UC without PSC. The ALP values were raised to a mean of 3.7 times the upper normal limit (observed range, 1.5-5.5 times the upper normal limit). Aspartate aminotransferase was moderately elevated in most patients, but no other abnormal biochemical liver test results were observed at onset. The results of our study indicate that PSC is the major cause of raised ALP values in patients with UC; thus cholangiography should be performed in UC patients with unexplained elevated ALP levels. A prognostic indicator is needed to predict the individual prognosis and to determine the optimal timing of liver transplantation.

Adolescent↗
PubMed1991

Availability of mesalazine (5-aminosalicylic acid) from enemas and suppositories during steady-state conditions.

The local and systemic bioavailability of a mesalazine enema (Pentasa, Ferring A/S, Denmark) and a mesalazine suppository (Pentasa, Ferring) was assessed during steady-state conditions. Eleven healthy subjects took 1 g of the enema or the suppository twice daily for 1 week, with a drug-free period of at least 1 week in between. At the end of each treatment period the urine and faeces were collected for 48 h, and the concentrations of mesalazine and the metabolite acetyl-mesalazine were measured. Plasma concentrations of drug and metabolite were measured hourly during a 12-h dose interval. The faecal water concentration of mesalazine was significantly higher after suppository treatment (55.7 mmol/l) compared with enema treatment (31.7 mmol/l) (p less than 0.01). The systemic absorption was low; 15% of daily mesalazine dose was recovered in urine after enema treatment and 10% after suppositores (p less than 0.01). Plasma concentrations were low, and no accumulation of either mesalazine or acetyl-mesalazine occurred. In conclusion, the enema and the suppository can be continuously administered as 1 g of mesalazine twice daily, respectively, giving high faecal water concentrations of mesalazine and a low systemic absorption.

Administration, Rectal↗
PubMed1990

Measurement of gastrointestinal pH and regional transit times in normal children.

Gastrointestinal pH and regional intestinal transit times of a capsule were measured in twelve healthy children aged 8-14 years using a radiotransmitting pH-sensitive capsule. The location of the capsule was determined by fluoroscopy. pH in the stomach was 1.5, but rose to 6.4 in the duodenum (mean values). pH gradually rose in the small intestine and reached an alkaline peak value of 7.4 in the distal part. pH dropped to 5.9 in the cecum but rose to 6.5 in the rectum. Median gastric residence time of the capsule was 1.1 h. Small intestinal transit time was 7.5 h, and colonic transit time was 17.2 h. pH profile and intestinal transit times found in the present study are almost identical to values found in studies on healthy adults. It is therefore concluded that the release pattern of pH-dependent sustained-release tablets in children is likely to be equal to that of adults.

Adolescent↗
PubMed1990

Gastrointestinal pH and transit times in healthy subjects with ileostomy.

Gastrointestinal pH in 11 healthy subjects with ileostomy was determined with a pH-sensitive, radiotransmitting capsule. Median pH was 7.0 in duodenum, dropped to pH 6.3 in the proximal part, but rose to 7.3 in the distal part of the small intestine. In five subjects the pH of the ileostomy effluents was determined with the pH capsule as well as with a pH meter. Median pH was 7.2 measured with the capsule and 7.4 with the pH meter. The difference between the results obtained with the two methods ranged from 0.1 to 0.3 pH units. The median gastrointestinal transit time of the capsule was 10.5 h (range 6.2-12.8 h). Gastric residence time was 0.6 h (range 0.2-3.8 h), and small intestinal transit time was 10.3 h (range 5.6-11.9 h). Thus the small intestinal transit time in ileostomates is slightly increased compared with values reported from studies on subjects with intact gut. However, no statistically significant correlation was found between the small intestinal transit time and the time elapsed after the creation of the ileostomy. We conclude that colectomy does not alter small intestinal pH but seems to increase the small intestinal transit time of single units.

Adult↗
PubMed1990

Topical and systemic availability of 5-aminosalicylate: comparisons of three controlled release preparations in man.

The bioavailability of three pure 5-aminosalicylic (5-ASA) preparations (Asacol, Claversal, and Pentasa) was studied in 8 ileostomy patients and 12 normal subjects after 6 days of treatment with 2000 mg 5-ASA. The local bioavailability, reflected by the 5-ASA concentration was thereby measured at two clinically relevant areas of the gut: at the entrance to, and the exit from the colon. Estimates of the systemic bioavailability were obtained from the urinary excretions and the plasma values of 5-ASA and Acetyl-5-ASA (Ac-5-ASA) during the three regimens. The three preparations studied are designed to release 5-ASA at different levels in the intestine, but there was no significant difference in the 5-ASA concentrations in the ileostomy effluents (Asacol 1.8 mmol/L, Claversal 3.4 mmol/L, Pentasa 2.0 mmol/L, median values). However, we found a smaller urinary excretion of 5-ASA and Ac-5-ASA (5.2% vs Claversal 27.9% and Pentasa 23.0%, median values of ingested daily dose) and a lower concentration of Ac-5-ASA in the ileostomy effluents after Asacol treatment (0.8 mmol/L, median value) which indicates a more distal release from this preparation compared with Claversal (2.4 mmol/L, median value) and Pentasa (5.5 mmol/L, median value). In normal subjects a higher faecal water concentration of 5-ASA was found after Asacol (9.8 mmol/L, median value) compared with Claversal (5.0 mmol/L, median value), whereas no difference between the faecal water concentrations of Ac-5-ASA was found (Asacol 21.5 mmol/L, Claversal 21.6 mmol/L, median values). This can be explained by a larger systemic absorption of 5-ASA from Claversal, and accordingly Claversal treatment resulted in the largest urinary excretion of 5-ASA and Ac-5-ASA (43.7% vs Asacol 35.6% and Pentasa 31.6%, median values of ingested daily dose). The high Ac-5-ASA concentration in the ileostomy effluents and in the faeces after Pentasa, and the low plasma values, indicate a slow 5-ASA release from this preparation throughout the small and large intestine. The results of the study indicate that Asacol is released in the distal part of the small intestine, that Pentasa is gradually released in the small and large intestine, and that Claversal shows an intermediate release pattern.

Administration, Topical↗
PubMed1989

Low-dose cyclosporin for Crohn's disease: implications for clinical trials.

Cyclosporin is a potent immunosuppressant, which has gained recent interest as a possible treatment for Crohn's disease. Chronic nephrotoxicity, however, has recently been demonstrated as a result of early treatment with high initial cyclosporin doses. We report the effect of a 3-month treatment with low-dose cyclosporin (5-7.5 mg kg-1 day-1) in 11 chronically active, therapy-resistant Crohn's disease patients. Eight of the 11 patients (72%) improved according to a clinical grading score and the Dutch Activity Index whereas 9/11 (82%) improved according to the Crohn's Disease Activity Index (P less than 0.05) after 1 month. Three patients were withdrawn despite clinical improvement. One developed arterial hypertension, one dropped out and one required surgical treatment due to a small bowel stricture. Five patients (45%) completed the treatment period with improved clinical scores. After tapering-off, two patients (18%) were better at follow-up. No serious side-effects were encountered and it is concluded that low-dose cyclosporin treatment should be further investigated in Crohn's disease.

Adult↗