Library

Notes: Background : Fibroblast growth factors play an important role in (patho)physiological processes such as wound healing and tissue repair. We previously showed that basic fibroblast growth factor is actively involved in inflammatory bowel disease processes. In the present retrospective study, we assessed whether serum basic fibroblast growth factor levels in Crohn's disease patients reflect the response to anti-tumour necrosis factor-α antibody infliximab treatment.Aim and methods : Serum samples, biopsies and patient data from a subgroup of patients included in two placebo-controlled trials were used. Fistulizing Crohn's disease patients (n = 42) were administered placebo or infliximab intravenously three times and evaluated for response up to 18 weeks. Biopsies from a subgroup of patients were stained for basic fibroblast growth factor using indirect immunohistochemistry. In the active Crohn's disease trial, patients (n = 24) received either placebo or infliximab once, and disease activity and serum basic fibroblast growth factor were assessed at weeks 0 and 4.Results : Basic fibroblast growth factor levels at inclusion were comparable in the fistulizing Crohn's disease patients regardless of whether the fistulas did or did not respond or completely heal (median range: 9.3–10.6 pg/mL). At the end of follow-up basic fibroblast growth factor levels were lower in patients who responded (9.2 pg/mL, P = 0.06) or who were completely healed (8.9 pg/mL, P = 0.009) when compared with patients did not respond/heal (14.5 pg/mL), the latter not significantly increased from baseline. Decreases in the perianal disease activity index and open fistula scores at the end of the follow-up were significantly correlated with the decrease in basic fibroblast growth factor (R = 0.41; P = 0.012 and R = 0.35; P =0.027, respectively). Immunohistological evaluation also showed a trend towards decreased basic fibroblast growth factor expression in intestinal biopsies of these patients. Patients with active disease, i.e. a Crohn's disease activity index ≥220 combined from the two studies, were found to have significantly (P = 0.0046) lower baseline serum basic fibroblast growth factors levels than those with inactive disease (5.3 vs. 10.3pg/mL, respectively). Treatment of the active disease patients did not affect the serum basic fibroblast growth factor level, although a general decrease in disease activity was observed with infliximab treatment.Conclusions : Healing of fistulizing/perianal Crohn's disease seems to be reflected by a decrease in high serum basic fibroblast growth factor. Basic fibroblast growth factor levels do not relate with response in active Crohn's disease patients.

Notes: Immediately after the introduction of the proton pump inhibitor lansoprazole, a 2-year follow-up study was started to evaluate patterns of use, safety and effectiveness of this drug in naturally occurring groups of patients in the Netherlands. Medical data were recorded by participating physicians while medication listings were provided by pharmacists.〈section xml:id="abs1-2"〉〈title type="main"〉Methods:The study was designed according to the Safety Assessment of Marketed Medicines guidelines. The only inclusion criterion was the use of lansoprazole prior to entry into the study.〈section xml:id="abs1-3"〉〈title type="main"〉Results:A total of 5669 lansoprazole users was included by 374 general practitioners and 117 specialists. Lansoprazole was mostly prescribed in patients with reflux oesophagitis (55.1%), `gastritis' (26.8%) and duodenal ulcers (11.4%), sometimes as part of a Helicobacter pylori eradication therapy (8.5%). For their complaints most patients (91.1%) had previously used acid-related drugs. Improvement or disappearance of complaints was achieved in 88.9% and 90.5% of patients after 4 and 8 weeks of treatment, respectively. Diarrhoea (4.1%), headache (2.9%) and nausea (2.6%) were the most frequently reported adverse events.〈section xml:id="abs1-4"〉〈title type="main"〉Conclusion:The patterns of use of lansoprazole in daily practice deviated from the recommendations in the information leaflet. Nevertheless, lansoprazole was found to be safe in this naturally occurring group of users. Effectiveness appeared to be comparable to results found in clinical trials of the registered indications for lansoprazole.

Notes: The effects of oral indomethacin on intragastric pH and serum gastrin were investigated in rheumatoid arthritis patients. Nine patients (1 male, 8 female) without a history of peptic ulcer disease and 6 patients with a history of peptic ulcer disease (5 male, 1 female) were studied. To obviate Helicobacter pylori infection as a confounding factor, only patients with positive H. pylori serology were included. After a 5-day period of placebo treatment and after a 5-day period of indomethacin (50 mg t.d.s.; total dose 750 mg), 24-h intragastric pH and basal and meal-stimulated serum gastrin levels were measured in a double-blind placebo controlled cross-over study.There were no differences in the median 24-h pH values between placebo and indomethacin irrespective of peptic ulcer disease history. Indomethacin resulted in a higher basal and stimulated gastrin response than placebo in patients with a history of peptic ulcer disease. The basal and incremental responses were lower in patients with a history of peptic ulcer disease than in patients without a history of peptic ulcer disease, both during indomethacin and placebo. The same basal and stimulated incremental serum gastrin responses were found during placebo and indomethacin treatment in patients without a history of peptic ulcer disease. No correlation was established between median 2-h post-prandial intragastric pH and post-prandial incremental serum gastrin concentration. We conclude that indomethacin does not influence the intragastric pH of rheumatoid arthritis patients irrespective of history of peptic ulcer disease.

Notes: Objectives: Enteric-coated microsphere/microtablet pancreatin should stay intact in the stomach and dissolve promptly on entering the duodenum. Post-prandial intraluminal pH in the distal duodenum is 5.75 and is lower in exocrine pancreatic insufficiency. The aim of the study was to measure in vitro dissolution times in buffer solutions with pH 4.0–6.0 for five currently available enteric-coated microsphere/microtablet pancreatin preparations. Methods: The following preparations were tested: Creon, Creon Forte, Pancrease, Pancrease HL and Panzytrat. Two capsules were placed in the buffer solution at 37 °C in a USP dissolution testing apparatus. Buffer solutions with pH between 4.0 and 6.0 were used. Solutions were stirred at 125 r.p.m. and the rate of dissolution was monitored by taking 2-mL samples at regular intervals and measuring extinction at 280 nm. Measurements were repeated six times. Results: All preparations failed to dissolve at pH 4.0. At pH 5.0 Pancrease HL showed 43% dissolution within 30 min, all other preparations 15% or less. Panzytrat and Pancrease HL showed more than 50% dissolution within 30 min at pH 5.2. Panzytrat, Pancrease HL and Creon Forte had more than 90% dissolution within 30 min at pH 5.6, and all preparations more than 90% dissolution within 30 min at pH 5.8 and higher. Conclusions: For the treatment of exocrine panceatic insufficiency conventional strength enteric-coated microsphere/microtablet pancreatin preparations do not have an optimal dissolution profile. The newer, high lipase preparations such as Pancrease HL perform better, although still not optimally, at pH 5.4 and lower.

Notes: Eighteen patients with duodenal, gastric or jejunal ulcers, resistant to at least 3 months treatment with histamine H2-receptor antagonists, singly or in combination with other anti-ulcer drugs, were treated with 40 mg omeprazole once daily for up to 8 weeks. All ulcers healed, the majority within two weeks. After ulcer healing patients were given maintenance therapy with high doses of cimetidine or ranitidine. Of 15 patients on maintenance therapy with H2-receptor antagonists, 12 (80%) developed a relapse after a period ranging from 3 to 52 weeks. Two patients were lost to follow-up. After re-healing on 40 mg omeprazole, two patients were given 20 mg omeprazole daily as maintenance therapy but relapses occurred again after 14 and 26 weeks respectively. After re-healing on 40 mg omeprazole, these two patients and one additional patient received maintenance therapy with 40 mg omeprazole daily. At present these three patients have been relapse-free for periods varying from 16 to 52 weeks. No side effects were registered during treatment with omeprazole. It is therefore concluded that omeprazole is highly effective in healing refractory peptic ulcers and that omeprazole maintenance therapy may be useful for prevention of relapse.

Notes: Background: Corticosteroid therapy of patients with inflammatory bowel disease can give rise to systemic side-effects. Budesonide is a topically acting corticosteroid with low systemic bioavailability and is efficacious in the treatment of inflammatory bowel disease. Natural killer cells were previously found to be altered, both systemically and locally, in patients with inflammatory bowel disease. Modulatory effects of budesonide, prednisolone, dexamethasone, and cortisol on peripheral blood NK cells have already been described, but have never been assessed on mucosal NK cells from the intestine. Methods: The effect of the synthetic corticosteroids prednisolone and budesonide, the endogenous corticosteroid cortisol, and adrenocorticotropic hormone was analysed on NK cells isolated from the lamina propria of human intestinal resection specimens. Results: The three corticosteroids suppressed intestinal NK cell activity, not only during the cytotoxicity assay, but also after pre-incubation of the lamina propria mononuclear cells. ACTH, however, did not affect the activity of intestinal NK cells. We previously showed that corticosteroid-suppressed peripheral blood NK cell activity could be restored in vivo, but not in vitro, by the administration of ACTH. In the present study, the in vitro incubation of budesonide- or prednisolone-suppressed mucosal NK cells with cortisol, alone or combined with ACTH, did not revert the suppressed NK cell activity. These findings are similar to our previous observations with peripheral blood NK cells. Conclusions: Intestinal mucosal NK cells can be suppressed by systemically as well as locally acting corticosteroids. This suppression in NK cell activity is not reversed by incubation with cortisol and/or ACTH.

Notes: Background: Treatment of omeprazole induces profound inhibition of gastric acid secretion, resulting in hypergastrinaemia. In rats hypergastrinaemia induced by chronic administration of high doses of omeprazole resulted in ECL-cell hyperplasia and subsequent carcinoid formation. This finding may limit long-term therapy in man. The synthetic prostaglandin E2 analogue enprostil not only inhibits gastric acid secretion but also reduces serum gastrin in normal subjects and in peptic ulcer patients. The present study was undertaken to determine whether enprostil reduces serum gastrin in patients on long-term treatment with omeprazole. Methods: Eight patients with reflux oesophagitis treated with 40 mg omeprazole once daily for at least 3 months received 3 5 μg enprostil t.d.s. during a 5-day treatment course. Basal and postprandial serum gastrin concentrations and pepsinogen A and C levels were measured on the day before, the first and the final day, and on the day after cessation of treatment. Results: Enprostil significantly (P 〈 0.05) reduced basal serum gastrin from 65±15 pmol/L to 51 ± 13 pmol/L on the first treatment day, and to 41 ± 9 pmol/L on the final day. Enprostil also significantly (P 〈 0.05) reduced postprandial integrated serum gastrin from 6173 ± 849 pmol.h/L to 4516 ± 906 pmol.h/L and to 3532 ± 706 pmol.h/L on the first and final treatment days, respectively. On the day after cessation of treatment basal (57± 11 pmol/L) and postprandial integrated serum gastrin concentrations (5766 ± 864 pmol.h/L) were not significantly different when compared to pretreatment values. Enprostil had no significant influence on serum pepsinogens A and C. Conclusion: Short-term co-administration of enprostil lowers the serum gastrin levels in patients on long-term treatment with omeprazole.

Notes: Primed continuous infusion and repeated intravenous injections of ranitidine (daily dose 200 mg) were compared in a homogeneous population of postoperative intensive care unit patients in a randomized fashion. Intragastric pH was measured continuously for 72–96 h with combined glass electrodes positioned in the gastric corpus. Patients whose intragastric acidity fell below pH 4.0 for 70% of a 24-h period within 48 h after the operation (baseline period) were considered ‘at risk’ of developing stress-related lesions. From the 26 patients screened, 18 fulfilled this criterion. Nine received the continuous infusion regimen (50 mg bolus+0.125 mg.kg/h) and nine received repeated boluses (50 mg ranitidine every 6 h). A consistent decrease of intragastric acidity was shown in each group by a rise in 24-h median pH from 1.4 (1.3–1.7; 26th–75th percentile) during the baseline period to 4.2 (1.9–5.4, P 〈 0.01) for the continuous infusion and from 1.55 (1.1–2.2) to 2.65 (2.1–3.5, P 〈 0.02) for the repeated boluses during the final 24 h of the therapy period. During that period intragastric pH was maintained above 4 for 52% of time by continuous infusion and for 40% of time for repeated boluses compared with 10.8% (P= 0.01) and 6.2% (P= 0.008) of time, respectively, in the baseline period. In conclusion, although no statistically significant differences between the two regimens could be detected, the continuous infusion regimen tended to show slightly better results in percentages of time that pH values were above 1 to 7, and in median 24–h pH values.

Notes: Disturbances in zinc metabolism have been documented in patients with inflammatory bowel disease. In this study we evaluated the effect of in vivo treatment with zinc on the in vitro natural killer cell activity in thirteen inflammatory bowel disease patients, with stable disease and mild–moderate disease activity, in a double-blind randomized cross-over trial. The results of our study show a long-lasting effect of in vivo zinc administration, which decreased peripheral blood natural killer cell activity in inflammatory bowel disease.

Notes: Aim: To study the effect of oral budesonide and prednisolone on peripheral blood natural killer (NK) cell activity in patients with active ileocaecal Crohn's disease (Crohn's disease activity index, CDAI ≧ 200). Methods: One group of patients was treated for 10 weeks with oral budesonide (n= 9; 9 mg/day), and another group of patients for the same period with prednisolone (n= 9; 40 mg/day). Budesonide was tapered to 6 mg/day after 8 weeks and prednisolone after 2 weeks to 5 mg/day in the last week. Before treatment, and at 2, 4 and 10 weeks of treatment, natural killer cell activity was determined with a 51Cr release assay, and the number of CD16+ NK cells by Fluoresence activated cell sorter (FACS) analysis. Results: Budesonide, as well as prednisolone treatment, significantly decreased natural killer cell activity at weeks 2 and 4. This decrease was found to be accompanied by a similar decrease in the number of CD16+ NK cells. At 10 weeks, natural killer cell activity had almost returned to pre-treatment levels in the budesonide group and was significantly higher than pre-treatment levels in the prednisolone group. Disease activity was significantly decreased in all patients at week 2 until the end of the trial period. Conclusion: Both budesonide and prednisolone treatment suppress peripheral blood natural killer cell activity of patients with active ileocaecal Crohn's disease by decreasing the numbers of CD16+ NK cells in the circulation.