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Biomedical subjects

H Goebell

Publications and source records attributed to H Goebell.

At least 91 records · Page 5Linked to original sources
PubMed1994

A comparison of budesonide with prednisolone for active Crohn's disease.

BACKGROUND: Patients with active Crohn's disease are often treated with corticosteroids, but the treatment has many side effects. Budesonide is a potent, well-absorbed corticosteroid, but because of a high rate of first-pass metabolism in the liver, its systemic bioavailability is low. METHODS: We conducted a randomized, double-blind, 10-week trial comparing the efficacy and safety of an oral controlled-release form of budesonide with the efficacy and safety of prednisolone in 176 patients with active ileal or ileocecal Crohn's disease (88 patients in each treatment group). The dose of budesonide was 9 mg per day for eight weeks and then 6 mg per day for two weeks. The dose of prednisolone was 40 mg per day for two weeks, after which it was gradually reduced to 5 mg per day during the last week. RESULTS: At 10 weeks, 53 percent of the patients treated with budesonide were in remission (defined as a score < or = 150 on the Crohn's disease activity index), as compared with 66 percent of those treated with prednisolone (P = 0.12). The mean score on the Crohn's disease activity index decreased from 275 to 175 in the budesonide group and from 279 to 136 in the prednisolone group (P = 0.001). Corticosteroid-associated side effects were significantly less common in the budesonide group (29 vs. 48 patients, P = 0.003). Two patients in the prednisolone group had serious complications (one had intestinal perforation and one an abdominal-wall fistula). The mean morning plasma cortisol concentration was significantly lower in the prednisolone group than in the budesonide group after 4 weeks (P < 0.001) and 8 weeks (P = 0.02) of therapy, but not after 10 weeks. CONCLUSIONS: Among patients with active Crohn's disease, both controlled-release budesonide and prednisolone are effective in inducing remission. In this trial, prednisolone reduced scores on the Crohn's disease activity index more, whereas with budesonide there were fewer glucocorticoid-associated side effects and less suppression of pituitary-adrenal function.

Adult↗
PubMed1994

Two molecular forms of peptide YY (PYY) are abundant in human blood: characterization of a radioimmunoassay recognizing PYY 1-36 and PYY 3-36.

Two endogenous forms of PYY are abundant in man and dog, PYY 1-36 (PYY-I) and PYY 3-36 (PYY-II). PYY-II is a major molecular form of PYY in human colon, but it is not known, whether PYY-II is also released into the circulating blood. Several radioimmunoassays for measuring PYY-I in plasma have been developed, but it has not been reported, whether they equally detect PYY-II. We characterize a radioimmunoassay for measuring PYY in human plasma which equally recognizes PYY-I and PYY-II. Using this radioimmunoassay and reversed phase HPLC we demonstrate the existence of two forms of PYY in human blood, coeluting with synthetic PYY-I and PYY-II.

Adult↗
PubMed1994

Dyspepsia in healthy blood donors. Pattern of symptoms and association with Helicobacter pylori.

Whether Helicobacter pylori is causally linked to dyspepsia remains controversial. The aims of this study were to assess in healthy blood donors the prevalence of dyspepsia and dyspepsia subgroups, determine if H. pylori is associated with different categories of dyspeptic symptoms, and evaluate the association between dyspepsia and nicotine, alcohol, and analgesic use. Consecutive blood donors (N = 180) who had no clinical evidence of organic disease were included. Abdominal symptoms were measured by means of a standardized questionnaire that has been previously validated. Subjects with dyspepsia (defined as pain localized to the upper abdomen) were further subdivided into those with ulcer-like, dysmotility-like, reflux-like, or nonspecific dyspepsia. A total of 65 subjects reported abdominal pain or discomfort during the prior 12 months [36.1%, 95% confidence interval (CI) 29.1-43.1]; 44 subjects (24.4%, 95% CI 18.2-30.7) had dyspepsia. Dysmotility-like, reflux-like, and ulcer-like symptoms were reported by 19.4% (95% CI 13.7-25.2), 17.2% (95% CI 11.7-22.7), and 16.7% (95% CI 11.2-22.1) of subjects with dyspepsia, respectively. Fifty-seven subjects (31.7%, 95% CI 24.9-38.5) were H. pylori positive; 26% of subjects with H. pylori and 24% without H. pylori had dyspepsia (P > 0.50). The seroprevalence of H. pylori was also similar among the different categories of dyspepsia. We conclude that infection with H. pylori is not associated with abdominal complaints in otherwise healthy subjects.

Adolescent↗
PubMed1994

RUDER--a prospective, two-year, multicenter study of risk factors for duodenal ulcer relapse during maintenance therapy with ranitidine. RUDER Study Group.

In a prospective study of the risk factors for duodenal ulcer relapse during maintenance (150 mg daily) ranitidine therapy, 1899 patients with chronic ulcer disease were recruited to a multicenter, German trial. Healing of all ulcers was confirmed endoscopically; endoscopy was also obligatory after one and two years or if the patients presented in the interim with symptoms of ulcer relapse. By the end of the first year, 247 patients had experienced at least one relapse and, by the end of the second year, 432 patients had relapsed at least once. The crude one- and two-year relapse rates were 13.0% (95% CI 11.5-14.5) and 22.7% (20.9-24.6%), respectively. Univariate analysis indicated that all seven prospectively defined risk factors were associated with an increased two-year relapse rate; of these, duodenal erosions distant from the healed ulcer [odds ratio (95% CI): 2.23 (1.59-3.15); P < 0.0001], smoking, past or present [1.46 (1.12-1.90); P = 0.0050], psychological stress [1.38 (1.09-1.74); P = 0.0085], heavy physical labor [1.45 (1.06-1.98); P = 0.0219], and absence of NSAID intake [1.54 (1.01-2.29); P = 0.0464] were independent risk factors on stepwise logistic regression analysis, whereas persistent symptoms at healing [1.29 (1.03-1.62), P = 0.0310] and frequent prior relapses [1.45 (1.01-2.04); P = 0.0454] were not. Multiple relapses in 107 patients [5.63% (4.60-6.67%)] were associated with duodenal erosions, smoking, stress, and heavy physical labor.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Characterization of two forms of peptide YY, PYY(1-36) and PYY(3-36), in the rabbit.

Peptide YY (PYY) has been purified as a 36 amino acid peptide from intestinal extracts of several mammalian species including pig, rat, dog, and man. The primary structure of rabbit PYY is still unknown, although rabbit tissues have extensively been used for characterization of PYY receptor subtypes and receptor subtype-mediated actions. We report the purification and primary structure of PYY(1-36) (PYY-I) from rabbit intestinal mucosa, and the existence of a second endogenous molecular form of PYY, PYY(3-36) (PYY-II). The amino acid sequence of PYY-I is YPSKPEAPGEDASPEELNRYYASLRHYLNLVTRQRY-amide. Rabbit PYY differs from porcine PYY, which is identical to rat and canine PYY, by two amino acid substitutions at positions 3 (Ser instead of Ala) and 18 (Asp instead of Ser), whereas rabbit PYY and human PYY differ by only one residue at position 3 (Ser instead of Ile). The existence of two endogenous forms of PYY in the rabbit, with PYY-II lacking the amino-terminal dipeptide Tyr-Pro of PYY-I, is consistent with previously reported findings, demonstrating the existence of PYY-II in man and dog (9,11). We have previously demonstrated that PYY-I is an unselective Y1/Y2 agonist, whereas PYY-II is a highly selective Y2 agonist. Thus, proteolytic processing of PYY-I controls the peptide's receptor selectivity. The existence of PYY-I and PYY-II in the rabbit supports the assumption of a physiological role of Y receptor heterogeneity for PYY.

Amino Acid Sequence↗
PubMed1994

Gastroenterologic manifestations of mastocytosis.

Mastocytosis as a rare disease is usually diagnosed by dermatologists because of urticaria pigmentosa as one of the leading signs. If the triad of urticaria pigmentosa, flush and diarrhea is present diagnosis is easily made. However, urticaria pigmentosa and flush may be less dominant or even absent and gastrointestinal signs may render diagnosis more difficult. Therefore, this review is thought to describe clinical manifestations of mastocytosis from the gastroenterologist's point of view. In addition, on the grounds of a recent classification of mastocytosis practical diagnostic procedures as well as therapeutic approaches are discussed.

Acute-Phase Proteins↗
PubMed1994

[Prospective study of the incidence and prevalence of ulcerative colitis in a large urban population in Germany (western Ruhr area)].

A prospective epidemiological study of the incidence and prevalence of ulcerative colitis was conducted from 1980 to the end of 1984. The population at risk comprised 1.6 million inhabitants in the four industrial cities Essen, Duisburg, Mülheim and Oberhausen of the western Ruhr-area. All 35 hospitals of the area with 79 departments of internal medicine, surgery and pediatrics with in- and outpatients took part in the study. 225 patients with substantial ulcerative colitis (excluded proctitis) were newly diagnosed during the study period (129 men, 96 women); patients suffering only from ulcerative proctitis were not included. The mean incidence was 2.9 new cases per 100,000 inhabitants and year ranging from 2.3 to 3.7 without significant difference between these 5 years. Incidence figures were somewhat higher for men (3.5) than for women (2.4) and this difference was significant (p < 0.05). The age- and sex-adjusted incidence was found to have a broad range for both sexes between 20 and 65 years of age without a high incidence-peak in young adults or a second peak later in life. Additionally all formerly diagnosed cases of ulcerative colitis were registered during this time period and the hospital archives were looked backward for prevalent cases til 1975 retrospectively. From all these cases the prevalence of ulcerative colitis at December 31, 1984 was calculated for 27.3 patients per 100,000 inhabitants (n = 417) similarly with a significant preponderance of men against women (31.1 vs. 22.1 per 100,000 inhabitants, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Endogenous somatostatin possibly controls pancreatic growth: further evidence for feedback regulation.

Specific inhibitors acting upon pancreatic proteinases in the gut can cause pancreatic hypertrophy ('growth'), which is probably mediated through a feedback mechanism utilizing cholecystokinin. We have proposed the involvement of somatostatin, and here test the hypothesis that endogenous somatostatin secreted into pancreatic juice may regulate pancreatic growth. Groups of rats were given the proteinase inhibitor camostate intragastrically for either 3, 7, 14, 28, or 56 days, when they were sacrificed. In some groups the pancreata were weighed and homogenized while in other groups isolated perfused pancreatic organ preparations were performed. Somatostatin was measured in the homogenates, pancreatic juice and portal vein effluents. In camostate-fed animals, pancreatic weights increased to a maximum at 28 days, while pancreatic somatostatin content increased significantly from the third day onwards, and somatostatin secretion into pancreatic juice increased progressively until day 28. In contrast, somatostatin secretion into portal blood remained unchanged from those of untreated controls over the duration of the experiment, and its concentration was lower than in pancreatic juice. These observations provide further evidence that endogenous pancreatic somatostatin may control pancreatic growth in rats.

Animals↗
PubMed1993

Effect of cysteamine on insulin release and exocrine pancreatic secretion in vitro.

Cysteamine is known to deplete somatostatin from pancreatic D cells. In the isolated perfused rat pancreas we investigated its effects on somatostatin and insulin release as well as exocrine pancreatic secretion in the presence of 16.7 mM glucose and 180 pM CCK-8. At a concentration of 0.1 mM, cysteamine had no significant effect on pancreatic endocrine and exocrine functions. At 10 mM, however, cysteamine released somatostatin (380 +/- 70 vs 100 +/- 20 fmol/20 min), inhibited insulin output (890 +/- 120 vs 13210 +/- 3260 mu units/20 min) and reduced exocrine pancreatic secretion (volume: 12 +/- 2 vs 20 +/- 2 microliters/20 min; lipase: 31 +/- 3 vs 60 +/- 7 units/20 min). We conclude that the complex changes induced by cysteamine are consistent with a physiological role of endogenous somatostatin in the regulation of insulin release. The reduction of exocrine pancreatic secretion, however, was at least in part, if not completely, mediated via the insuloacinar axis rather than a direct effect of cysteamine-released somatostatin on pancreatic acinar cells.

Animals↗
PubMed1993

Oral contraceptive use and cigarette smoking in Crohn's disease.

Previous studies have consistently found strong positive associations between smoking and Crohn's disease. The association between oral contraceptive use and Crohn's disease remains, however, controversial. In order to analyze whether smoking and oral contraceptive use are independent risk factors, a case-control study was performed. In 90 women with Crohn's disease and 90 community controls information was assessed about their smoking habits and their use of oral contraceptives. Smoking and oral contraceptive use were associated with one another. After adjusting for oral contraceptive use, the relative risk for smokers compared with nonsmokers was 3.0 (1.3-6.8). After controlling for smoking, the relative risk estimates for oral contraceptive use were for no use, 1-3 years, and > 3 years of use 1.0, 2.5 (1.0-6.6), and 4.3 (1.3-14.4), respectively. When oral contraceptive use was stratified by smoking habits, the data show that oral contraceptives only increased the risk for Crohn's disease in nonsmokers. From the lack of increase in risk for combined exposure, it is concluded that both factors might act through a common mechanism.

Adult↗
PubMed1993

Comparison of clearance and metabolism of infused cholecystokinins 8 and 58 in dogs.

BACKGROUND: Cholecystokinin (CCK) 58 is the predominant molecular form of CCK in canine and human intestine and circulating blood. There is no report on the metabolism and clearance rate of CCK-58. The aim of this study was to compare the in vivo half-life and metabolism of CCK-58 with that of synthetic CCK-8. METHODS: CCK-58 was purified from canine intestine by consecutive high-performance liquid chromatographic (HPLC) and fast protein liquid chromatographic steps. The peptides were given to 12 dogs as an intravenous (IV) bolus injection to determine the half-life of circulating CCK. Six dogs were given CCK-58 or CCK-8 as a constant IV infusion to determine plasma clearance rates and stability in circulating blood. Circulating molecular forms of CCK were determined by radioimmunoassay after extraction of CCK from plasma and characterization by HPLC. RESULTS: The half-life of CCK-58 was 4.4 +/- 0.6 minutes compared with 1.3 +/- 0.1 minutes for CCK-8. Less than 5% of CCK-58 could be detected as smaller forms during constant IV infusion. CONCLUSIONS: The longer half-life of CCK-58 compared with CCK-8 and the minimal conversion into smaller forms during constant IV infusion are consistent with the finding that CCK-58 is not only the major stored form but also the circulating form of CCK after endogenous stimulation in dogs.

Animals↗
PubMed1993

Pancreastatin--a mediator in the islet-acinar axis?

Pancreastatin was isolated from porcine pancreas in 1986 and has been shown to inhibit insulin release and exocrine pancreatic secretion in vivo. In the isolated perfused rat pancreas, we investigated its effect on the exocrine pancreas and evaluated its indirect effects mediated via the islet-acinar axis. In the presence of 16.7 mmol/L glucose, 20 pmol/L, 200 pmol/L, and 2 nmol/L pancreastatin reduced insulin release but did not affect exocrine pancreatic secretion stimulated by cholecystokinin (CCK), secretin, or bombesin. Pancreastatin also failed to affect unstimulated exocrine pancreatic secretion. In the presence of 1.7 mmol/L glucose, 200 pmol/L and 2 nmol/L pancreastatin inhibited glucagon release and potentiated CCK-stimulated exocrine pancreatic secretion. Inhibition of glucagon release and augmentation of exocrine pancreatic secretion may be independent phenomena, but they could be linked by the islet-acinar axis. Thus we speculate that a pancreastatin-induced inhibition of glucagon release may indirectly have caused augmentation of exocrine pancreatic secretion.

Animals↗
PubMed1993

Modulation of human periodic interdigestive gastrointestinal motor and pancreatic function by the ileum.

Following ingestion of a meal, unabsorbed nutrients may reach the distal intestine partly after the termination of the prandial period, i.e., in the presence of interdigestive motor and secretory patterns. To determine if interdigestive motility and pancreatic enzyme secretion are modulated by the delivery of nutrient into the ileal lumen, six fasting volunteers were intubated with an oroileal multilumen tube system that permitted multiple small intestinal manometry, gastric and duodenal aspiration, and perfusions of marker and test solutions. Ileal perfusions of nutrient or saline solutions were started during phase I of the interdigestive motility cycle. Ileal perfusion with carbohydrate or lipids increased the duration of motor quiescence and decreased the length of the interdigestive cycle, mainly by decreasing the proportion of phase II activity compared with ileal saline (p < 0.01). Pancreatic outputs of amylase, trypsin, and chymotrypsin prior to ileal perfusions were low because, due to the protocol, perfusions were started during phase I. With ileal saline, enzyme outputs increased (p < 0.05) in association with the occurrence of phase II motility, as expected. By contrast, ileal carbohydrate and triglyceride perfusion prevented the phase II-associated increase in enzyme outputs (p < 0.05). The data suggest that the presence of nutrients within the ileal lumen may modulate interdigestive motor and pancreatic functions.

Adult↗
PubMed1993

Prospective multicentre study of risk factors associated with delayed healing of recurrent duodenal ulcers (RUDER). RUDER Study Group.

Risk factors for delayed duodenal ulcer healing during treatment with ranitidine (300 mg daily) were examined in a multicentre German study of 1923 patients with endoscopically proved, recurrent duodenal ulceration. Healing rates, per protocol, were 39.5% at two weeks, 70.9% at four weeks, and 93.2% at eight weeks. Prospective testing of five, predefined risk factors indicated that smoking (p = 0.0039) was associated with a decreased healing rate at two weeks. Frequent prior recurrence (p = 0.464), a heavy physical workload (p = 0.145), and psychological stress (p = 0.062) were not associated with a decreased healing rate and there were too few patients at risk to allow assessment of the effect of regular NSAID intake. Exploratory analysis identified prior slow healing, a large ulcer, multiple ulcers, and prior ulcer complications, in addition to smoking, as markers of slow healing. In the absence of these risk factors, the mean healing time was 3.3 weeks (95% confidence interval 3.0, 3.5), rising to 3.7 weeks (3.5, 3.9) for one, 4.4 weeks (4.1, 4.7) for two, and 5.1 weeks (4.5, 5.6) for three to five risk factors. Delayed duodenal ulcer healing is associated with multiple factors whose effect is cumulative; for patients with two or more of five easily identified risk factors, more than four weeks' treatment with a histamine H2 receptor antagonist is required to achieve ulcer healing.

Adult↗
PubMed1993

Oroileal transit of slow release 5-aminosalicylic acid.

The predominant active anti-inflammatory moiety in chronic inflammatory bowel disease is 5-aminosalicylic acid (5-ASA). As unprotected 5-ASA is rapidly absorbed in the upper gastrointestinal tract several slow release preparations have been developed to permit passage of 5-ASA to the lower small bowel and to the colon. To investigate luminal kinetics and extent of the release of 5-ASA intraluminal concentrations and loads of this compound together with that of its main metabolite acetyl-5-aminosalicylic acid (ac-5-ASA) were studied, over 15 hours after giving the slow release preparation Salofalk at a dose of 500 mg orally together with a test meal. Plasma concentrations and urinary excretion were also measured. Six healthy volunteers swallowed an 11 lumen oroileal tube, which allowed marker perfusion, aspiration of luminal content from the duodenum, mid-jejunum, and ileum, and recording of intestinal motility. Emptying of 5-ASA into the duodenum started after emptying of the meal, together with the first phase III of interdigestive motility. Mean luminal concentrations of 5-ASA and ac-5-ASA increased continuously from duodenum (both: 15 to 30 micrograms/ml) to ileum (60 to 110 micrograms/ml and 80 to 150 micrograms/ml respectively) over three hours and decreased over the next three hours. During 10 hours after eating, 30% of the total dose passed the ileum in solution and another 10% were excreted in urine. Thus about 60% reached the colon unreleased from tablets and another 30% were in solution. The ratio of 5-ASA and ac-5-ASA in solution was about 1:1 in the duodenum and 1:1.5 to 1:2 in the more distal small intestine. The data suggest that the large quantities of intraluminal ac-5-ASA are generated in the intestinal mucosa and reach the lumen by back diffusion. The results show that most of the 5-ASA from this slow release preparation is delivered into the colon, which explains its effectiveness in ulcerative colitis. The considerable luminal concentrations already present in the distal ileum might justify therapeutic trials in Crohn's disease.

Administration, Oral↗