Oral xylose isomerase decreases breath hydrogen excretion and improves gastrointestinal symptoms in fructose malabsorption - a double-blind, placebo-controlled study.

BACKGROUND: Incomplete resorption of fructose results in increased colonic hydrogen production and is a frequent cause of abdominal symptoms. The only treatment available is diet. AIM: To study whether orally administered xylose isomerase (XI), an enzyme that catalyses the reversible isomerisation of glucose and fructose, can decrease breath hydrogen excretion in patients with fructose malabsorption. METHODS: Patients received 25 g fructose in 100 mL water together with either placebo or XI capsules. Primary endpoint was the reduction in breath hydrogen excretion, as assessed by the area under the breath hydrogen curve over 4 h (AUC). A secondary endpoint was the reduction in abdominal pain, bloating and nausea assessed on a visual analogue scale (VAS, range: 0-10). A P value <0.05 was considered statistically significant. RESULTS: Sixty-five patients in whom fructose malabsorption had been diagnosed by positive breath hydrogen test within the previous year, were included in the study [15 males, 50 females; mean age 43.3 (s.d. = 14.4), range: 21-73 years]. The median AUC was 885 ppm/240 min in the XI group compared to 2071 ppm/240 min in the placebo group (P = 0.00). Median scores for abdominal pain (0.7 vs. 1.3) and nausea (0.2 vs. 0.6), but not for bloating (P = 0.053), were significantly improved after XI (P = 0.009 and P = 0.005) as compared with placebo. CONCLUSIONS: Oral administration of xylose isomerase significantly decreased breath hydrogen excretion after ingestion of a watery fructose solution. Nausea and abdominal pain were significantly improved by xylose isomerase.

Effects of lactulose and polyethylene glycol on colonic transit.

BACKGROUND: The effects of lactulose and polyethylene glycol on colonic transit are poorly established. AIM: To assess the effects of these laxatives on colonic transit in normal subjects. METHODS: Colonic transit (mean residence time, cumulative counts in stool, counts remaining in the proximal or distal colon) was measured scintigraphically in normal subjects on the second and third day of a 3-day ingestion of 67-134 g/day lactulose, or 59 g/day polyethylene glycol. RESULTS: At similar stool weight (lactulose: 653 +/- 120 g/day; polyethylene glycol: 522 +/- 66 g/day), transit was significantly slower during 99 g/day lactulose when compared with 59 g/day polyethylene glycol; this was most pronounced in the distal colon (mean residence time: lactulose - 403 +/- 55 min; polyethylene glycol - 160 +/- 41.9 min). Short chain fatty acid concentration in 24-h stool correlated significantly with counts remaining in the distal colon at 12 h (r = 0.79, P = 0.001). Increasing lactulose doses were significantly associated with increasing stool weight (r = 0.79) and shorter mean residence time in the total (r = -0.56) and distal colon (r = -0.64). The sum of faecal carbohydrates plus short chain fatty acids was associated with stool weight (r = 0.95, P < 0.001). CONCLUSION: Lactulose accelerates colonic transit. However, compared with polyethylene glycol, transit during lactulose is prolonged.

Chemical nociception in the jejunum induced by capsaicin.

BACKGROUND AND AIMS: Chemonociception in the human small intestine has not been studied extensively. Although capsaicin can cause intestinal sensations, it is not known if this is due to stimulation of chemoreceptors or to motor changes. Our aims were to evaluate motor activity during capsaicin induced nociception and to compare qualities of jejunal nociception induced by capsaicin and mechanical distension. METHODS: Twenty nine healthy subjects swallowed a tube with a perfusion site at the ligament of Treitz and, 7 cm distally, a barostat balloon. Phasic motor activity was measured around the perfusion site and the balloon. Capsaicin solutions (40, 200, and 400 microg/ml) 2.5 ml/min were perfused for 60 minutes or until severe discomfort occurred. A graded questionnaire for seven different sensations was completed every 10 minutes and after capsaicin perfusion was replaced by saline perfusion because of severe discomfort. Sensations arising from pressure controlled distensions were assessed before and after capsaicin perfusion when sensations had stopped (n = 19), or during capsaicin administration when no discomfort was reported (n = 5). RESULTS: Capsaicin perfusion induced feelings of pressure, cramps, pain, and warmth. The quality and abdominal location of these sensations were similar to those induced by distension, except for warmth (p<0.01) and pressure (p<0.05). Seven of 12 subjects receiving 40 microg/ml capsaicin and all subjects receiving higher capsaicin concentrations developed discomfort. Perfusion had to be stopped after 55 (3.3), 15 (5.7), and 10 (2.2) minutes with 40, 200, and 400 microg/ml capsaicin, respectively, whereafter the sensations disappeared within 10 minutes. Repeated capsaicin (200 microg/ml) applications significantly reduced the time until discomfort occurred (p = 0.01). Jejunal tone was not altered by capsaicin but phasic activity proximal to the perfusion site was reduced during capsaicin induced discomfort (p<0.001). Pain thresholds during distensions were not different before and after capsaicin perfusion. CONCLUSION: Despite the similarities in abdominal localisation and perceptional quality of capsaicin and distension induced sensations, our results rule out the fact that abdominal discomfort evoked by capsaicin involves sensitisation of mechanoreceptors or an increase in phasic and tonic motor activity. Capsaicin evokes abdominal sensations by stimulation of chemoreceptors which proves the existence of chemonociception in the human small intestine.

Endotoxin pretreatment modifies peristalsis and attenuates the antipropulsive action of adrenoceptor agonists in the guinea-pig small intestine.

The action of endotoxin to alter gastrointestinal motility in vivo may reflect a direct effect on the gut or result from vascular and other systemic manifestations of this sepsis model. Here we examined whether in vivo pretreatment of guinea-pigs with endotoxin modifies peristalsis in the isolated gut and influences the antipropulsive action of adrenoceptor agonists. Distension-induced peristalsis was recorded in fluid-perfused segments of the small intestine taken from animals pretreated intraperitoneally with endotoxin (1 mg kg(-1)Escherichia coli lipopolysaccharide) or vehicle 4 or 20 h before. Clonidine, adrenaline, noradrenaline, dopamine and dobutamine inhibited peristalsis with differential potency. Endotoxin pretreatment lowered the peristaltic pressure threshold and altered other parameters of baseline peristalsis in a time-related manner. The potency and efficacy of clonidine to inhibit peristalsis were markedly decreased after endotoxin administration, while the potency of the other test drugs was less attenuated. The antipropulsive action of clonidine in control segments was reduced by yohimbine and prazosin, whereas in segments from endotoxin-pretreated animals it was antagonized by yohimbine but not prazosin. We conclude that systemic endotoxin pretreatment of guinea-pigs modifies baseline peristalsis by an action on the gut and inhibits the antipropulsive action of adrenoceptor agonists through changes in adrenoceptor activity.

Effect of pantoprazole on the course of reflux-associated laryngitis: a placebo-controlled double-blind crossover study.

BACKGROUND: The optimal management of patients with reflux-associated laryngitis is unclear. We performed a placebo-controlled crossover trial in patients with proven reflux disease and associated laryngitis to determine the effect of pantoprazole and to gain information on the natural course of the disease. METHODS: Sixty-two consecutive non-smoking patients with hoarseness and proven laryngitis were examined. Scores with respect to the larynx and for subjective complaints were determined and 24-h pH-metry to assess acid reflux in the lower oesophagus and pharynx was performed. Patients with pathologic reflux were given the chance to enter a double-blinded randomized crossover trial with pantoprazole 40 mg b.i.d. and placebo for a duration of 3 months each, separated by a 2-week washout period. RESULTS: Twenty-four of 62 patients showed pathological reflux; 21 patients were included in the study and 14 concluded all parts of the study. Both pantoprazole and placebo resulted in a marked improvement in laryngitis scores (decrease of 8.0 +/- 1.4 versus 5.6 +/- 2.6; no significant difference between the 2 treatments) and symptoms after the first 3 months (decrease of oesophageal symptom score of 2.2 +/- 1.4 versus 5.4 +/- 2.8; decrease of laryngeal scores of 8.3 +/- 3.6 versus 10.3 +/- 3.9; also no significant difference between the 2 treatments). A second pH-metry 2 weeks thereafter proved the persistence of reflux in most of these patients. Switching to pantoprazole led to a further improvement of scores. In the group switched to placebo there was recurrence only in a minority of patients. CONCLUSIONS: The self-limited nature of reflux-associated laryngitis in non-smokers is largely underestimated. Laryngitis improves despite the persistence of reflux. Pantoprazole may be helpful especially in relieving acute symptoms, but the advantage of long-term treatment over placebo has been greatly overestimated.

Effect of sildenafil on oesophageal motor function in healthy subjects and patients with oesophageal motor disorders.

BACKGROUND AND AIMS: Sildenafil blocks phosphodiesterase type 5 which degrades nitric oxide (NO) stimulated 3'5'-cyclic monophosphate (cGMP), thereby relaxing smooth muscle cells in various organs. We used sildenafil as a tool to investigate the role of the NO-cGMP pathway in the oesophagus of healthy volunteers and patients with hypercontractile oesophageal motility disorders. METHODS: Six healthy male volunteers participated in a randomised double blind study on two separate days before and one hour after oral intake of either sildenafil 50 mg or placebo. Oesophageal manometry was performed to determine vector volume of the lower oesophageal sphincter (LOS) and pressure amplitudes of the oesophageal body. Four of the volunteers underwent 12 hour ambulatory oesophageal manometry on two separate days, once with sildenafil 50 mg and once with placebo. An activity index for spontaneous swallowing was calculated for every hour of the study. Eleven patients with hypercontractile oesophageal motility disorders took part in an open study of the effect of 50 mg sildenafil on manometric features of their disorder and on the clinical response to sildenafil taken as required. RESULTS: In healthy subjects, sildenafil significantly reduced LOS pressure vector volume and pressure amplitudes in the distal half of the oesophageal body. In three of four subjects the inhibitory effect of sildenafil lasted at least eight hours. In nine of 11 patients, manometric improvement after sildenafil was observed but only four had an improvement in oesophageal symptoms with sildenafil taken as required. Two of these four patients however experienced side effects and did not want to continue treatment. CONCLUSIONS: Sildenafil lowers LOS pressure and propulsive forces in the body of the oesophagus of healthy subjects as well as in patients with nutcracker oesophagus, hypertensive LOS, and achalasia. The effect of sildenafil on the oesophageal body may last for up to eight hours in healthy volunteers. A subset of patients with hypertensive LOS or nutcracker oesophagus may benefit from sildenafil but side effects are a limiting factor.

Low potential of dobutamine and dopexamine to block intestinal peristalsis as compared with other catecholamines.

OBJECTIVE: Catecholamines are frequently used in critically ill patients to restore stable hemodynamics and to improve organ perfusion. One effect of short-term or long-term administration of catecholamines may be inhibition of propulsive motility in the intestine. We therefore analyzed the effect of dopexamine, dobutamine, and dopamine on ileal peristalsis and compared their action with that of epinephrine and norepinephrine, which have long been known to suppress intestinal peristalsis. DESIGN: In vitro study on excised guinea pig ileum segments. SETTING: Laboratory for experimental studies at the University. SUBJECTS: Isolated guinea pig ileum. INTERVENTIONS: Segments of ileum excised from guinea pigs were mounted in a tissue bath in Krebs-Henseleit solution and bubbled with 95% oxygen/5% CO2. Luminal perfusion with the same solution was performed at a rate of 0.35 mL/min. The bath temperature was kept at 36.5 degrees C. Peristalsis was recorded via changes in the intraluminal pressure. The drugs under investigation (dopamine, epinephrine, norepinephrine, dobutamine, and dopexamine) were added to the tissue bath. MEASUREMENTS AND MAIN RESULTS: Low concentrations of each catecholamine, except epinephrine, caused a decrease in the pressure threshold, which reflects a stimulatory effect on peristalsis. Higher catecholamine concentrations caused a concentration-related increase in the threshold, cumulating in a complete block of peristalsis. The rank order of inhibitory potency was epinephrine > norepinephrine > dopamine > dobutamine approximately dopexamine. Dobutamine and dopexamine were about 500-fold less active than epinephrine in suppressing peristalsis. CONCLUSIONS: This study shows that dobutamine and dopexamine have the least potential to block propulsive motility in the intestine, whereas epinephrine demonstrates the most adverse inhibitory effect. Because at low concentrations dobutamine and dopexamine even stimulate peristalsis, these drugs appear to be superior compared with other catecholamines with regard to their direct effects on intestinal motility.

[Polyethylene glycol (Macrogol)--an overview of its use in diagnosis and therapy of gastrointestinal diseases]. / Polyäthylenglykol (Macrogol)--Ubersicht über seine Verwendung in der Diagnostik und Therapie gastroenterologischer Erkrankungen.

The pharmacological rationale for the use of polyethylene glycol (PEG) in gastroenterology is its inverse relation between molecular mass and intestinal absorbability, with practically no intestinal absorption at molecular masses exceeding 3000, its lack of intestinal enzymatic degradation or bacterial metabolism, and its water binding capacity. PEG is used as a nonabsorbable marker in the evaluation of small intestinal and colonic absorption and secretion, as a marker for intestinal permeability studies, as an essential component of colonic lavage solutions used for the preparation of the colon for diagnostic and therapeutic interventions, and for the treatment of fecal impaction or chronic constipation. Since PEG has been used for decades, there is extensive data documenting its safety in short term use. Although animal experiments have also proved the safety of chronic PEG administration, the increasing use of PEG for the treatment of chronic constipation in the long term requires further surveillance to establish its safety.

Effects of postprandial walking on delayed gastric emptying and intragastric meal distribution in longstanding diabetics.

OBJECTIVE: We investigated the influence of standardized postprandial walking on the rates of gastric emptying and of intragastric meal distribution in 50 consecutive patients with longstanding insulin-dependent diabetes mellitus. METHODS: Gastric emptying of a semisolid meal labeled with 99mTc was continuously recorded with a dual-head gamma camera with patients in the supine position for 90 min before and 20 min after a 30-min postprandial walk. Regions of interest enclosing total stomach, and proximal and distal gastric compartments were calculated to determine gastric emptying rates and intragastric meal distribution. RESULTS: The evaluation of gastric emptying rates before and after postprandial walking demonstrated two variants of delayed gastric emptying: one variant that was counteracted by postprandial walking in seven patients (14%, Group I) and another variant that was not influenced by postprandial walking in 11 patients (22%, Group II). In addition, the emptying rates of 28 patients (56%) were within the range of controls and in four patients the emptying was accelerated (8%). The filling of the proximal gastric compartment was predominant and remained dominant after walking in Groups I and II. In controls and in diabetics with normal gastric emptying, the preliminary predominant filling of the proximal compartment was equalized after walking and the proximal compartment regained predominance thereafter. The changes in gastric emptying characteristics from delayed to accelerated gastric emptying may be related to the duration of diabetes (r = -0.47, p<0.03) and were not indicated by symptoms of upper GI discomfort or by secondary diabetic manifestations. CONCLUSION: Postprandial walking may improve gastric emptying in 14% of patients with longstanding insulin-dependent diabetes mellitus.

Mechanisms and management of antibiotic-associated diarrhea.

Only 10%-20% of all cases of antibiotic-associated diarrhea (AAD) are caused by infection with Clostridium difficile. Other infectious organisms causing AAD include Clostridium perfringens, Staphylococcus aureus, Klebsiella oxytoca, Candida species, and Salmonella species. Most of the clinically mild AAD cases are due to functional disturbances of intestinal carbohydrate or bile acid metabolism, to allergic and toxic effects of antibiotics on intestinal mucosa, or to pharmacological effects on motility. Saccharomyces boulardii and Enterococcus SF68 can reduce the risk of developing AAD. Patients receiving antibiotic treatment should avoid food containing high amounts of poorly absorbable carbohydrates. Mild cases of AAD that may or may not be caused by C. difficile can be resolved by discontinuation of antibiotic therapy and by dietary carbohydrate reduction. Only severe AAD caused by C. difficile requires specific antibiotic treatment.

Rectal tone, distensibility, and perception: reproducibility and response to different distensions.

Increasing interest is focusing on the role of intestinal tone, distensibility, and mechanosensation in the genesis of abdominal symptoms. Experimental approaches usually feature balloon distension of the bowel with measurements of perception, tone, and compliance and/or elastance; however, the methodologies are standardized incompletely. We examined the reproducibility of repeated assessments of sensory perception, basal tone, and compliance and/or elastance of the rectum during distension. We also evaluated the response to inflations that varied in regard to control of pressure or volume, pattern of distension, and rate of inflation. Five healthy volunteers were studied under two separate protocols. The first featured a series of experiments on each of 5 days; the other consisted of 2 separate days of study. Repeated distensions evoked reproducible responses of sensation and compliance and/or elastance on a single day, providing a conditioning distension preceded them. Day-to-day variability was also sufficiently small to allow valid comparisons to be made on different days in healthy persons. The configuration of the distension profile (phasic, staircase, or ramp) and the rate of inflation (from 1 to 40 ml/s) had little effect on distensibility or perception. Perceptions were sometimes transient and sometimes constant, but no relationship was found between these temporal features and the magnitude of the stimulus. These observations help provide a basis as to how the responses to rectal distension can be best studied.

Intraluminal capsaicin does not affect fluid and electrolyte absorption in the human jejunum but does cause pain.

BACKGROUND: Stimulation of sensory nerves with capsaicin regulates ion transport in the small intestine in animal experiments. AIM: To investigate whether sensory nerves that are stimulated by capsaicin administration influence fluid and electrolyte absorption in the human jejunum in vivo. METHOD: Intestinal perfusion studies were performed in 12 healthy subjects using a four lumen tube with a proximal occlusion balloon and a plasma-like electrolyte solution. After an initial control period, 5 (n = 3), 10 (n = 8), or 50 (n = 1) micrograms/ml capsaicin was added to the perfusate, and this was followed by a final control period. Rates of absorption of water, sodium, potassium, chloride, and bicarbonate were determined in a 30 cm segment of jejunum using a non-absorbable volume marker. RESULTS: At all three concentrations of capsaicin there were no significant changes in water and electrolyte absorption as compared with control periods. Two subjects who received 10 micrograms/ml and the subject receiving 50 micrograms/ml experienced crampy abdominal pain. CONCLUSION: The results do not support the hypothesis that capsaicin sensitive afferent nerves are involved in the physiological regulation of net absorption or secretion across the human jejunal mucosa. Chemical stimulation of these nerves, however, gives rise to abdominal pain.

Hyperkalaemia and diarrhoea in a patient with surreptitious ingestion of potassium sparing diuretics.

We report a patient who presented with the unusual combination of chronic diarrhoea and hyperkalaemia. The patient was admitted to our hospital after repeated negative evaluations elsewhere including exploratory laparotomy. The patient had a long history of diarrhoea with hypokalaemia which was documented on several occasions in the past. Several months before admission to our hospital for evaluation of diarrhoea the patient developed hyperkalaemia. Her daily stool output reached 1200 g and her serum potassium was as high as 6.0 mmol/l. Extensive evaluation revealed surreptitious ingestion of the diuretics triamterene, hydrochlorothiazide and spironolactone as the cause of hyperkalaemia and diarrhoea. In addition, she had melanosis coli which was interpreted to be the consequence of surreptitious ingestion of anthraquinone-containing laxatives in the past although no current laxative intake could be proven. We postulate that diarrhoea in our patient was mainly due to the decreased sodium absorption in the small intestine and colon caused by diuretics. Serum aldosterone levels were more than eight times the upper limit of normal. Increased aldosterone levels presumably arose secondary to volume contraction and sodium chloride depletion, but presumably were not able to affect renal and colonic electrolyte transport because of blockage of mineralocorticoid receptors by spironolactone. Thus, the unusual combination of diarrhoea and hyperkalaemia resulted.

Evidence of accelerated gastric emptying in longstanding diabetic patients after ingestion of a semisolid meal.

UNLABELLED: This study investigated the prevalence of accelerated gastric emptying in 40 consecutive nonselected patients with longstanding insulin-dependent diabetes mellitus (range 11-54 yr; mean 27 yr). METHODS: The gastric emptying of a semisolid meal labeled with 99mTc was continuously recorded with a dual-head gamma camera for 90 min in patients who were supine. RESULTS: Eleven patients demonstrated delayed gastric emptying, but three male diabetics showed accelerated gastric emptying with retention values that were different from controls already after 10 min of recording (89% +/- 3% versus 96% +/- 4%; p < 0.02). During the 90-min segment, accelerated gastric emptying reduced initial gastric contents to 11% +/- 8% (p < 0.001) as compared to 50% +/- 10% in control subjects and 78% +/- 6% (p < 0.001) in patients with delayed gastric emptyings. Accelerated gastric emptying was characterized by an almost equal initial meal distribution in proximal and distal compartments of stomach, both emptying approximately 90% of their contents within 90 min. Normal and delayed gastric emptying was characterized by a 60%-40% initial ratio of meal distribution between gastric compartments. During normal emptying, both compartments reduced contents with approximately 50%, but delayed gastric emptying was caused by only a 15% reduction of proximal contents accompanied by a 34% reduction in distal contents. CONCLUSION: Recording in the supine position to abolish gravitational influences demonstrated accelerated gastric emptying of a firm semisolid meal with a prevalence of 8%. However, delayed gastric emptying was shown as the predominant gastric manifestation of longstanding insulin-dependent diabetes mellitus with a prevalence of 28%.

Assessment of the influence of hydrogen nonexcretion on the usefulness of the hydrogen breath test and lactose tolerance test.

The recognition of hydrogen nonexcretion in up to 20% of tested subjects and the large ethnic differences in the prevalence of lactose malabsorption make it necessary to reassess the diagnostic usefulness of the lactose tolerance test and the hydrogen breath test. Both tests were performed in 83 consecutive patients with suspected lactose malabsorption who ingested 50 g lactose. On a separate day a hydrogen breath test was performed after 25 g lactulose. The prevalence of hydrogen nonexcretion was 18%. The diagnostic usefulness of hydrogen breath test was influenced both by the individual threshold for hydrogen excretion and the amount of malabsorbed lactose. In addition to baseline values, breath samples for hydrogen measurements have to be taken at 30, 60, 90, 180, and 240 minutes after ingestion of lactose. For the lactose tolerance test only one measurement of serum glucose at 30 minutes is needed in addition to the baseline measurement. The combination of both tests excludes the influence of hydrogen nonexcretion, but even if a combined diagnostic approach utilizing the lactose hydrogen breath test and lactose tolerance test is used, 6% of patients presenting with symptoms suggestive of lactose intolerance cannot be classified.