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Biomedical subjects

G Holtmann

Publications and source records attributed to G Holtmann.

At least 73 records · Page 4Linked to original sources
PubMed1999

Randomised double-blind comparison of simethicone with cisapride in functional dyspepsia.

AIM: To compare the efficacy of simethicone with cisapride in patients with functional (non-ulcer) dyspepsia. METHODS: After standardized diagnostic work-up and at least 6-days wash-out of medication, 177 patients with functional dyspepsia were enrolled; 173 of them (age 19-71 years) were randomized and treated using a double-dummy technique with simethicone (84 mg t.d.s.) or cisapride (10 mg t.d.s.). At baseline and after 2 and 4 weeks, the intensity of the symptoms was scored from 0 (absent) to 3 (severe) using a standardized symptom questionnaire. Efficacy of the treatment was judged by the patients as 'very good', 'good', 'moderate' or 'no effect'. RESULTS: A total of 166 patients completed the trial. After 2 and 4 weeks, 34% and 46% (respectively), of the patients treated with simethicone judged the improvement in symptoms to be excellent compared to 13% and 22% (respectively) of patients treated with cisapride (P < 0.01). After 2 weeks the difference in the improvement in the global symptom score was significantly better (Delta30.7%, P < 0.001) for simethicone than for cisapride, while this difference failed statistical significance after 4 weeks (Delta10.2%, P=0.11). CONCLUSIONS: In patients with functional dyspepsia, simethicone relieves symptoms during the first 2 weeks of treatment significantly better than cisapride.

Cisapride↗
PubMed1999

Alosetron relieves pain and improves bowel function compared with mebeverine in female nonconstipated irritable bowel syndrome patients.

BACKGROUND: Irritable bowel syndrome is one of the most common gastrointestinal disorders, yet no therapy convincingly controls the multiple symptoms of this syndrome. AIM: To compare the efficacy and tolerability of the new 5-HT3-receptor antagonist alosetron and the smooth muscle relaxant mebeverine in a double-blind, multicentre, randomized trial. METHODS: Six hundred and twenty-three nonconstipated females with irritable bowel syndrome were randomized to receive alosetron 1 mg twice daily (n=319) or mebeverine 135 mg three times daily (n=304) for 12 weeks, followed by a 4-week post-treatment period. The primary efficacy end-point was monthly responders for adequate relief of irritable bowel syndrome related abdominal pain and discomfort (defined as patients reporting adequate relief on at least 2 out of 4 weeks). Secondary end-points included assessments of bowel function, including urgency, stool frequency and stool consistency. RESULTS: There were significantly more responders in the alosetron group compared with mebeverine at months 2 and 3 (P < 0.01). Compared with mebeverine, the alosetron group experienced significant decreases in proportion of days with urgency and mean stool frequency, and had firmer stools within 1 week of starting treatment. A similar proportion of patients reported adverse events in the two treatment groups. CONCLUSIONS: In nonconstipated female irritable bowel syndrome patients, alosetron is significantly more effective than mebeverine in improving symptoms.

Adolescent↗
PubMed1998

Nonischemic chest pain induced by coronary interventions: a prospective study comparing coronary angioplasty and stent implantation.

BACKGROUND: Chest pain frequently occurs without any signs of ischemia within the first 24 hours after coronary interventions. To test the hypothesis that this pain may be due to local vessel injury ("stretch pain"), we performed a prospective study enrolling patients after PTCA, stent implantation, or diagnostic coronary angiography alone. METHODS AND RESULTS: A total of 145 patients after coronary angiography were evaluated by a validated questionnaire for quantifying postinterventional chest pain within 24 hours. To detect myocardial ischemia, all patients were evaluated with a 12-lead ECG and cardiac isoenzymes immediately after the procedure and the morning after. After stent implantation, 21 of the 51 patients (41.2%) developed chest pain, compared with 4 of the 33 patients (12.1%) undergoing PTCA and 6 of the 61 patients (9.8%) with a diagnostic angiography (P<0.001). Of these 31 patients who developed chest pain, only 3 (9.7%) felt that the pain was similar to previously experienced angina pectoris. The minimal lumen diameter after intervention was significantly larger in the stent group than in the PTCA group (3.14+/-0.75 versus 1.95+/-0.67 mm; P<0. 001). No patient had changes in the ECG compared with before intervention, but 3 patients after stent implantation had a rise in cardiac isoenzymes. No other major adverse cardiac events occurred until discharge. CONCLUSIONS: Nonischemic chest pain develops in almost half of all patients undergoing stent implantation and seems to be related to vessel overexpansion caused by the stent in the diseased vessel segment.

Aged↗
PubMed1998

Nomenclature of dyspepsia, dyspepsia subgroups and functional dyspepsia: clarifying the concepts.

There is international agreement that dyspepsia refers to pain or discomfort centered in the upper abdomen. However, the term 'discomfort' has been variably defined. While other symptoms may often be simultaneously present, gastro-oesophageal reflux disease can usually be clearly distinguished by the presence of predominant heartburn. Dyspepsia is a frequent reason for consultation in primary care and in gastrointestinal practice. With the widespread availability and utilization of endoscopy, it has become evident that a structural (or organic) explanation is found in only a minority of patients presenting with dyspepsia. Operationally, functional dyspepsia is defined as persistent or recurrent dyspepsia for 3 or more months in the absence of a clinically identifiable structural disease causing the symptoms. It has been proposed, based on symptoms, that functional dyspepsia be subdivided into symptom subgroups to promote patient homogeneity. The initially proposed 'clustering' of symptoms into ulcer-like and dysmotility-like functional dyspepsia has proved a dismal failure because of the considerable overlap observed, the lack of stability over time and the failure to identify robust pathophysiological abnormalities or responses to therapy. A subcategorization based upon the most bothersome symptom is theoretically more attractive but needs to be prospectively and rigorously tested.

Dyspepsia↗
PubMed1998

Involvement of chloride channels in the receptormediated activation of longitudinal colonic muscle.

In gastrointestinal smooth muscle, intracellular Cl- is maintained at levels higher than its electrochemical equilibrium. Therefore, Cl- efflux through receptor-mediated opening of Cl- channels should result in membrane depolarization and may be sufficient to activate voltage-sensitive calcium channels (VSCCs). To determine the contribution of Cl- channels to receptor-mediated contraction of the longitudinal muscle layer of the rabbit distal colon, we studied the mechanical response of muscle strips to substance P, carbachol and potassium depolarization following the depletion of Cl- i, and in the presence of the Cl- channel blocker 5-nitro-2-(3-phenylpropyl-amino)-benzoate (NPPB). A 60-min incubation of tissues in a HEPES-buffered solution in which NaCl had been replaced by Na isethionate (or Na gluconate) in equimolar amounts resulted in disappearance of phasic contractions, and in a partially reversible reduction of the tonic response to substance P and carbachol, but not to KCl depolarization. When the agonist was applied to tissues in control solution, or to Cl-(-)depleted tissues in a solution in which Na+ was acutely replaced in equimolar amounts by N-methyl-D-glucosamine, the mechanical response to substance P and carbachol was almost abolished. Acute Na+ replacement alone without prior Cl- depletion did not abolish phasic contractions, but reduced the tonic response to substance P and carbachol. Similar to the effect of Cl- depletion, incubation of tissues in NPPB (6.6 x 10(-5) M) reduced the tonic response to substance P and carbachol, and abolished phasic contractions. These findings are consistent with a contribution of a Cl- channel to the receptor-mediated activation of colonic smooth muscle. In addition, the data suggest that transient Cl- channel mediated depolarizations may play a role in the generation of phasic contractions.

Animals↗
PubMed1998

Antibody response to specific H. pylori antigens in functional dyspepsia, duodenal ulcer disease, and health.

OBJECTIVE: The relationship between H. pylori and functional dyspepsia remains controversial. The aim of this study was to identify a potential link between the antibody response to specific H. pylori antigens and functional dyspepsia. METHODS: A total of 50 consecutive patients with functional dyspepsia, 50 patients with duodenal ulcer (DU), and 150 healthy blood donor control subjects with no history of peptic ulceration were studied. H. pylori status was determined by IgG antibodies using a validated ELISA. In H. pylori-positive subjects, antibodies against specific H. pylori antigens were identified by Western blot. RESULTS: All DU patients (100%; 95%; CI, 93-100), 30 of 50 patients with functional dyspepsia (60%; 95% CI, 45-74) and 65 of 150 (43.3%; 95% CI, 34.3-51) blood donor controls tested positive for H. pylori. Forty-six of 50 (92%; 95% CI, 81-98) DU patients tested positive for the 91 kDa antigen (vacA) compared with 46 of 65 (69%; 95% CI, 58-81) control subjects and 22 of 30 (73%; 95% CI, 54-88) functional dyspepsia patients (p < 0.01 DU versus controls). Similarly, the 120 kDa antigen (cagA) tended (p < 0.15) to be more prevalent in DU patients (82%; 95% CI, 69-91) compared with controls (69%; 95% CI, 57-80) but not functional dyspepsia (77%; 95% CI, 57-90). No specific H. pylori antigens were associated with dyspepsia subgroups. CONCLUSION: No specific H. pylori antigens are linked to functional dyspepsia.

Adolescent↗
PubMed1998

Altered vagal and intestinal mechanosensory function in chronic unexplained dyspepsia.

BACKGROUND: Abnormal visceral mechanosensory and vagal function may play a role in the development of functional gastrointestinal disorders. AIMS: To assess whether vagal efferent and afferent function is linked with small intestinal mechanosensory function. METHODS: In seven patients with functional dyspepsia, six patients with a history of Billroth I gastrectomy and/or vagotomy, and seven healthy controls, intestinal perception thresholds were tested by a randomised ramp distension procedure performed with a barostat device. On a separate day, an insulin hypoglycaemia test was performed to assess the plasma levels of pancreatic polypeptide (PP) in response to hypoglycaemia, as a test of efferent vagal function. RESULTS: First perception of intestinal balloon distension occurred at significantly lower pressures in patients with functional dyspepsia (median 19.3, range 14.7-25.3 mm Hg) compared with healthy controls (median 26.0, range 21.7-43.7 mm Hg, p < 0.01). Sensory thresholds were significantly lower in patients after gastrectomy (median 12.2, range 8.0-14.7 mm Hg, p < 0.05 versus all others). In healthy controls and patients with functional dyspepsia, insulin hypoglycaemia significantly (p < 0.001) increased plasma PP levels. However, only two out of seven patients with functional dyspepsia had a more than twofold increase in PP values whereas all healthy controls had a more than twofold increase in PP levels after insulin hypoglycaemia (p < 0.05). In contrast, there was no significant PP response in the gastrectomised patients (median 2%, range -10 to +23%). PP responses and visceral sensory thresholds were significantly correlated (r = 0.65, p < 0.002). CONCLUSIONS: The diminished PP response after insulin hypoglycaemia indicates disturbed efferent vagal function in a subgroup of patients with functional dyspepsia. The data also suggest that the intact vagal nerve may exert an antinociceptive visceral effect.

Adult↗
PubMed1997

[Upper gastrointestinal hemorrhage caused by necrotizing cholecystitis with gallstone perforation into the duodenum].

A 68-year-old woman suffering from severe upper gastrointestinal bleeding underwent an urgent laparotomy. A necrotizing cholecystitis was found. The source of the bleeding was the eroded cystic artery. Perforation of a giant gallstone led to a fistula into the duodenum. The gallstone was removed from the distal jejunum. The patient's postoperative course was uneventful. Later on a choledochal stenosis had to be treated by stenting. One year after the procedure the patient is alive and well.

Aged↗
PubMed1997

Altered postprandial motility in chronic pancreatitis: role of malabsorption.

BACKGROUND & AIMS: Intraileal nutrients modulate gastrointestinal motility, but effects of maldigestion on postprandial motility are unknown. The aim of this study was to compare motor responses with ileal nutrient exposure in health and pancreatic insufficiency after a meal or intraluminal perfusion. METHODS: After oroileal multilumen intubation for duodeno-jejuno-ileal sampling, marker perfusion, and motility recording, 14 normal subjects and 12 patients with severe pancreatic insufficiency received a labeled liquid meal twice, either with placebo or pancreatin. Effects of intraileal nutrient perfusion on fed motility induced by duodenal amino acid perfusion were also investigated. RESULTS: Compared with normals, untreated patients had greater cumulative ileal nutrient delivery (69 +/- 21 vs. 487 +/- 232 kJ), shorter fed pattern (196 +/- 22 vs. 131 +/- 14 minutes), greater 90% gastric emptying (163 +/- 12 vs. 128 +/- 10 minutes), and faster small intestinal transit (86 +/- 9 vs. 44 +/- 6 minutes). Pancreatin reversed these changes. Ileal nutrient perfusion converted fed into interdigestive-like motility in normals (7 of 8) and patients (4 of 5). CONCLUSIONS: In subjects with pancreatic insufficiency, a low-energy liquid meal induces shorter fed motor pattern associated with accelerated gastric emptying and intestinal transit compared with healthy subjects. Because changes responded to enzyme treatment and could be reproduced by ileal nutrient perfusion, ileal delivery of malabsorbed chyme may be involved as a mechanism.

Adult↗
PubMed1997

Survival of human pancreatic enzymes during small bowel transit: effect of nutrients, bile acids, and enzymes.

The activity of pancreatic enzymes declines during aboral intestinal transit. We tested the hypothesis that survival of pancreatic enzyme activities during intestinal transit is affected by amounts or concentrations of calories, nutrients, bile acids, or pancreatic enzymes entering the segments of the small intestine. An oroileal tube was placed in 26 healthy humans. The tube had duodenal, jejunal, and ileal infusion ports for nonabsorbable markers and aspiration ports in the distal duodenum, distal jejunum, and distal ileum. Four infusates of different proportions of protein, fat, and carbohydrate were infused continuously into the duodenum at 40, 90, and 160 kcal/h. Of the nutrients infused into the proximal duodenum, 21 +/- 3, 51 +/- 7, and 39 +/- 5% of fat, protein, and carbohydrate, respectively, were delivered to the distal duodenum. During duodenoileal transit, lipase, chymotrypsin, amylase, and trypsin lost 71 +/- 5, 63 +/- 5, 43 +/- 7, and 38 +/- 9% of activity, respectively (P < 0.01 vs. distal duodenum). During duodenojejunal transit, the activity of each enzyme decreased more than 35% (P < 0.01 vs. distal duodenum), and infusion of more calories into the duodenum improved survival of all enzymes except trypsin (P < 0.05). During jejunoileal transit, greater amounts and concentrations of calories and carbohydrate improved survival of only lipolytic activity (P < 0.01, P < 0.05, respectively), and loss of lipolytic activity correlated directly with delivery of bile acids (r = 0.56, P = 0.05) and chymotrypsin (r = 0.80, P = 0.001) to the distal jejunum. We conclude that intraluminal nutrients increase survival of enzyme activities in the proximal intestine. After absorption of nutrients, the action of chymotrypsin and bile acids decrease lipolytic activity more than activity of other enzymes.

Adolescent↗
PubMed1997

Functional dyspepsia and irritable bowel syndrome: is there a common pathophysiological basis?

OBJECTIVES: Alterations of mechanosensitive thresholds occur in a subset of patients with functional dyspepsia and irritable bowel syndrome (IBS). However, symptoms associated with these two conditions frequently overlap. It is not known how often subjects with and without symptom overlap have abnormal intestinal sensory thresholds. Our objective was to assess the pattern of symptoms and small intestinal sensory thresholds in patients with functional disorders. METHODS: We studied 157 consecutive patients who had undergone extensive diagnostic work-up to exclude organic disease. Abdominal symptoms were assessed with a validated instrument, and patients were categorized as having functional dyspepsia, IBS, or both. With a barostat device, we tested small intestinal mechanosensitive function in 22 randomly selected patients from this population (with functional dyspepsia, IBS, or both) and 22 healthy controls. RESULTS: Sixty-seven patients (43%) reported simultaneous symptoms of functional dyspepsia and IBS, whereas symptoms of functional dyspepsia or of IBS alone occurred in 68 (43%) and 22 (14%) patients, respectively. Thresholds for first perception and maximum tolerated pressure (mm Hg +/-SD) were significantly lower in patients (21.0 +/- 2.0 and 31.0 +/- 1.0) than in controls (32.0 +/- 1.8 and 39.0 +/- 0.9, p < 0.001). However, thresholds for first perception and maximum tolerated pressure did not differ (p > 0.6) in patients with functional dyspepsia alone (20.1 +/- 3.2 and 28.9 +/- 2.5, n = 9), functional dyspepsia and concomitant IBS (19.9 +/- 2.7 and 30.7 +/- 2.2, n = 8), or IBS alone (23.5 +/- 2.3 and 33.3 +/- 3.0, n = 5). CONCLUSIONS: Small intestinal mechanosensitive pathways are disturbed in patients with functional dyspepsia and IBS. Differences in the pattern and localization of symptoms probably do not reflect differences in small intestinal sensory thresholds. Functional dyspepsia and IBS cannot be distinguished on the basis of altered small intestinal sensory thresholds.

Adult↗
PubMed1996

Association between H. pylori, duodenal mechanosensory thresholds, and small intestinal motility in chronic unexplained dyspepsia.

Alterations of small intestinal sensory thresholds and small intestinal dysmotility are associated with functional dyspepsia. Because gastric and duodenal afferents partly project to the same areas, we postulated that patients with functional dyspepsia and H. pylori infection would be characterized by lower duodenal sensory thresholds. We evaluated 16 patients with functional dyspepsia and 16 age- and sex-matched controls. All patients had undergone an extensive diagnostic work-up to exclude organic lesions. Mechanosensitive function was tested in the third portion of duodenum utilizing a barostat device, and small intestinal motility was assessed before and during duodenal nutrient infusion with a five-channel low-compliance perfusion system. H. pylori status was assessed by a validated serological test. Small intestinal sensory thresholds (first perception and maximal tolerated pressure) were significantly lower in patients (21.1 +/- 2.1 and 30.9 +/- 1.8 mm Hg) compared to controls (33.0 +/- 2.2 and 38.8 +/- 0.9 mm Hg, all P < 0.003). Nine of 16 patients compared with five of 16 controls were H. pylori positive (P = 0.15). Thresholds for H. pylori-negative (28.7 +/- 2.8 and 36.5 +/- 1.1 mm Hg) or -positive subjects (25.0 +/- 3.0 and 32.7 +/- 2.4 mm Hg) were overall not significantly different (P > 0.3). However, in patients with defined high H. pylori titers (>50 units/ml) defined a priori, thresholds for first perception were significantly lower (14.7 +/- 2.9 mm Hg, N = 5) compared to patients with H. pylori titers below this threshold (24.3 +/- 2.9 mm Hg, N = 4) or without H. pylori infection (23.8 +/- 3.4 mm Hg, P < 0.05). During duodenal nutrient infusion, the duodenal motility index increased (P < 0.03). This increase was not significantly different in patients and controls or in H. pylori-negative or -positive subjects. Sensory abnormalities are present in patients with functional dyspepsia. In a small subgroup of patients with high H. pylori titers, sensory abnormalities may be linked to H. pylori infection.

Adult↗