Search

Presents a letter to the editor in response to the case report "Pancreatic Necrosis Infection Due to Lactobacillus Paracasei in an Immunocompetent Patient," by W. J. Z'graggen, H. Frankhauser, F. Lammer, T. Bregenzer and D. Conen in a 2005 issue.

Objective: To evaluate whether enteral prophylaxis with probiotics in patients with predicted severe acute pancreatitis prevents infectious complications., Design: Multicentre, randomised, double-blind, placebo-controlled trial., Method: A total of 296 patients with predicted severe acute pancreatitis (APACHE II score > or = 8, Imrie score > or = 3 or C-reactive protein concentration > 150 mg/l) were included and randomised to one of two groups. Within 72 hours after symptom onset, patients received a multispecies preparation of probiotics or placebo given twice daily via a jejunal catheter for 28 days. The primary endpoint was the occurrence of one of the following infections during admission and go-day follow-up: infected pancreatic necrosis, bacteraemia, pneumonia, urosepsis or infected ascites. Secondary endpoints were mortality and adverse reactions. The study registration number is ISRCTN38327949., Results: Treatment groups were similar at baseline with regard to patient characteristics and disease severity. Infections occurred in 30% of patients in the probiotics group (46 of 152 patients) and 28% of those in the placebo group (41 of 144 patients; relative risk (RR): 1.1; 95% CI: 0.8-1.5). The mortality rate was 16% in the probiotics group (24 of 152 patients) and 6% (9 of 144 patients) in the placebo group (RR: 2.5; 95% CI: 1.2-5.3). In the probiotics group, 9 patients developed bowel ischaemia (of whom 8 patients died), compared with none in the placebo group (p = 0.004)., Conclusion: In patients with predicted severe acute pancreatitis, use of this combination of probiotic strains did not reduce the risk of infections. Probiotic prophylaxis was associated with a more than two-fold increase in mortality and should therefore not be administered in this category of patients.

Infection of pancreatic necrosis with intestinal flora is accepted to be a main predictor of outcome during severe acute pancreatitis. Bacterial translocation is the process whereby luminal bacteria migrate to extraintestinal sites. Animal models were proven indispensable in detecting three major aspects of bacterial translocation: small bowel bacterial overgrowth, mucosal barrier failure, and disturbed immune responses. Despite the progress made in the knowledge of bacterial translocation, the exact mechanism, origin and route of bacteria, and the optimal prophylactic and treatment strategies remain unclear. Methodological restrictions of animal models are likely to be the cause of this uncertainty. A literature review of animal models used to study bacterial translocation during acute pancreatitis demonstrates that many experimental techniques per se interfere with intestinal flora, mucosal barrier function, or immune response. Interference with these major aspects of bacterial translocation complicates interpretation of study results. This paper addresses these and other issues of animal models most frequently used to study bacterial translocation during acute pancreatitis.

Controlled distension of hollow organs is an accepted technique for generating reproducible visceral stimuli. We have constructed a new, flexible and intelligent distension system in which discomfort, pain and autonomic responses are recorded online. These responses can be fed back into the system in a regulatory loop and be used to shape the distension paradigm. Consequently, it is possible to take all subjects to a state of equal, although subjective, level of discomfort or pain, even though pressure, tension and volume might be totally different. By using a variable airflow, this new distension system can be effectively used in all kinds of paradigms, e.g. phasic, tonic, or ramp distensions or customized combinations of them. The system can be used to control pressure, volume or tension. A refinement of the system is that it is possible to automatically change the controlled entity during a distension, e.g. from an isobaric ramp directly into an isovolumetric tonic phase. Furthermore, the distension device allows double distensions with independent distension paradigms.

Acute pancreatitis has a high mortality in case of secondary infection of (peri-)pancreatic necrosis. Bacterial translocation is held responsible for the majority of these infectious complications of severe acute pancreatitis. Prophylactic strategies should therefore be directed at the three most important pathophysiological mechanisms of bacterial translocation: disturbed small-bowel motility and bacterial overgrowth, failure of the mucosal barrier function and a disturbed response of the immune system. In-vitro studies and research in experimental animals have shown that specially selected probiotics exert an effect on these mechanisms and can prevent bacterial translocation. Recently, several randomised, double-blind, placebo-controlled trials evaluating prophylactic treatment with enteral probiotics have shown good results. A Dutch multicentre trial, 'Probiotics in pancreatitis trial' (PROPATRIA), is currently underway.

Background: Indomethacin (Indo) exerts local toxic effects on small intestinal mucosa, possibly in association with hydrophobic bile salts. We investigated the potential toxic effects of Indo on ileal mucosa and the role of phosphatidylcholine (PC)., Materials and Methods: Transmucosal resistance and Na-fluorescein permeability of ileal mucosa segments from female Wistar rats were determined in Ussing chambers during a 30-min incubation with model systems containing: control-buffer, taurodeoxycholate (TDC), Indo, TDC-Indo, TDC-PC, or TDC-PC-Indo. Decrease of resistance and increase of permeability were considered as parameters for mucosal injury. After incubation in Ussing chambers, the histopathology was examined to quantify the extent of mucosal injury. Also, in CaCo-2 cells, LDH-release was determined as a measure of cytotoxicity, after incubation with various model systems., Results: Decrease of resistance and increase of permeability were highest in systems containing TDC-Indo (P < 0.01). Phosphatidylcholine protected against the cytotoxic effects of TDC in absence of Indo only. Extent of mucosal injury by histological examination was also highest in systems containing TDC-Indo (P = 0.006). Again, PC exhibited protective effects in absence of Indo only. The LDH-release by CaCo2-cells was strongest in TDC-Indo systems (P < 0.001)., Conclusions: Indomethacin disrupts protective effects of PC against bile salt-induced ileal mucosa injury. This finding is relevant for small intestinal injury induced by non-steroidal anti-inflammatory drugs.

This study investigated the relationship between the oesophageal acid exposure time and the underlying manometric motor events in patients with gastro-oesophageal reflux disease (GORD). In 31 patients, 3-hour oesophageal motility and pH were measured after a test meal. Ten patients underwent 24-hour ambulatory manometry and pH recording. In the 3-hour postprandial study, of 367 reflux episodes 79% was associated with a transient lower oesophageal sphincter relaxation (TLOSR), 14% with absent basal lower oesophageal sphincter (LOS) pressure and the remaining 7% with other mechanisms, representing 62, 28 and 10% of the acid exposure time, respectively. Acid reflux duration per motor mechanism was longer for absent basal LOS pressure than for TLOSR (189 +/- 23 s and 41 +/- 5 s, respectively, P < 0.001). In the 24-hour ambulatory study, the contribution of TLOSRs to reflux frequency vs acid exposure time were 65 vs 54% interprandially and 74 vs 53% after the meal. During the night, absence of basal LOS pressure accounted for 36% of reflux events representing 71% of acid exposure time. In conclusion, the duration of oesophageal acid exposure following a TLOSR is shorter than reflux during absent basal LOS pressure. TLOSRs are, the major contributor to oesophageal acid exposure during the day. At night, however, reflux during absent basal LOS pressure is the major contributor to acid exposure.

Background: With each swallow a certain amount of air is transported to the stomach. The stomach protects itself against excessive distention by swallowed air through belching (gas reflux). The mechanism of belching (transient lower oesophageal sphincter relaxation) is also one of the mechanisms underlying gastro-oesophageal reflux., Aim: To investigate whether swallowing of air leads to an increase in size of the intragastric air bubble and to gastro-oesophageal reflux., Methods: Multichannel intraluminal impedance measurement was used to quantify the incidence of swallowing of air in 20 healthy volunteers before and after a meal. Radiography was used to measure the size of the intragastric air bubble. Gastro-oesophageal reflux was assessed by concurrent impedance and pH measurement., Results: The rate of air swallowing was correlated to the size of the intragastric air bubble postprandially and to the rate of gaseous gastro-oesophageal reflux. The number of air swallows and the size of the intragastric air bubble did not correlate with the number of liquid acid and non-acid reflux episodes., Conclusions: In healthy subjects, air swallowing promotes belching but does not facilitate acid reflux.

In a young evolving science, there are always more questions than answers. That is also the situation in the emerging field of Probiotics, and this was made very clear at the International Probiotics Workshop in Amsterdam. In the report of this workshop, we present a selection of the most urgent questions in the field of probiotics. In addition, we propose a few strategies for the future of probiotics research. During the workshop, 120 experts--from disciplines including Human Nutrition, Gastroenterology, Nutritional Therapy, Cell Biology, Microbiology and Immunology--discussed new views on microbe-host interactions and the role of probiotics in prevention and alleviation of gastro-intestinal, atopic and auto-immune diseases. There is a general consensus among the experts that administering defined strains can help in preventing and curing gut flora related diseases: the first clinical trials show a promising role for probiotics. But the system is very complex, and most underlying mechanisms are still unclear. Rapid progress in this field will depend largely on the collaboration between fundamental researchers from different disciplines and medical specialists. Besides, more clinical studies are required to convince authorities and the public of the value of microbial therapies.

Alterations in L-arginine availability and nitric oxide (NO) synthesis in the intestinal muscularis may contribute to disturbed small intestinal motility that is observed during endotoxaemia. The aim of this study was to evaluate the effect of L-arginine infusion on visceral NO production and jejunal motility in hyperdynamic compensated endotoxaemic pigs. Fasted and saline-resuscitated pigs were intravenously infused for 24 h with endotoxin (lipopolysaccharide, 50 ng kg(-1) min(-1)) or saline (n = 6). Endotoxaemic pigs received either intravenous L-arginine (n = 6, 5.3 micromol kg(-1) min(-1)) or L-alanine (isocaloric, n = 6). After 24 h, intravenous L-arginine or L-alanine infusion was continued intragastrically for 32-h in an enteral meal. During (0-24 h) and 1 day postendotoxaemia (48-56 h), jejunal motility was recorded by manometry and analysed for migrating motor complex (MMC) characteristics. Visceral NO production was measured at 24 and 48 h by 15N2-arginine-to-15N-citrulline conversion. Visceral NO production was increased during endotoxaemia and was higher in L-arginine than in L-alanine-treated pigs. One day postendotoxaemia, visceral NO synthesis was still increased in L-arginine but not in L-alanine-treated animals. Endotoxaemia shortened the MMC cycle duration and accelerated the MMC propagation velocity. Both were restored by L-arginine. Similar motility disturbances were observed one day postendotoxaemia and were also compensated by L-arginine infusion.

Stretching the stomach wall in young healthy subjects causes an increase in muscle sympathetic nerve activity and in blood pressure, the gastrovascular reflex. We compared healthy elderly subjects with healthy young subjects to find out whether the gastrovascular reflex attenuates in normal ageing and we studied whether there was a difference in autonomic function or gastric compliance that could explain this possible attenuation. Muscle sympathetic nerve activity, finger blood pressure and heart rate were continuously recorded during stepwise isobaric gastric distension using a barostat in eight healthy young (6 men and 2 women, 27 +/- 3.2 years, mean +/-s.e.m.) and eight healthy elderly subjects (7 men and 1 woman, 76 +/- 1.5 years). Changes in cardiac output and total peripheral arterial resistance were calculated from the blood pressure signal. The baseline mean arterial pressure and muscle sympathetic nerve activity were higher in the elderly group (both P < 0.05) and muscle sympathetic nerve activity increase during the cold pressor test was lower in the elderly group (P = 0.005). During stepwise gastric distension, the elderly subjects showed an attenuated increase in muscle sympathetic nerve activity compared to the young subjects (P < 0.01). The older group tended to show a higher increase in mean arterial pressure (P = 0.08), heart rate (P = 0.06) and total peripheral arterial resistance (P = 0.09) The cardiac output rose slightly in both groups without significant difference between groups. The fundic compliance did not differ between groups. We conclude that stepwise gastric distension caused an increase in muscle sympathetic nerve activity in both groups, but the increase in the elderly was attenuated.

Background: Ileo-neorectal anastomosis (INRA), an alternative restorative procedure, was developed to reduce the pouch-related complication rate with an (at least) equal functional result., Methods: For this surgical outcome, data of all INRA patients, including bowel function and complications, were prospectively recorded. The reservoir capacity was determined repeatedly by physiologic tests. The anal sphincter complex was assessed by manometry and ultrasound examination. Evaluation of the neorectal mucosa was performed by endoscopy., Results: An INRA procedure was carried out in 39/53 selected patients (47 ulcerative colitis and 6 familial adenomatous polyposis). Fourteen UC cases were converted to ileal pouch anal anastomosis or proctectomy only, because of impossibility to completely remove the rectal mucosa or short of length of the rectal stump. The median operation time for INRA was 323 min (range 240-518), with 1,400 ml blood loss (400-4,500). The reservoirs were permanently defunctioned in 2 patients--one because of reclassification into Crohn's disease, and one with pouchitis refractory to medical treatment. In 18 out of 37 cases, web-like stenoses occurred at the mucosa-anal level, which were treated by single (9) or repeated (5) dilatation or surgical stenoplasty (2). No pouch-related complications like pelvic sepsis, fistula or sexual dysfunction occurred. Thirteen patients had episodes of 'pouchitis', successfully treated with antibiotics, and 7 other cases, with functioning reservoirs, also had proximal 'non-specific' (i.e. no histological criteria of Crohn's disease found) small bowel inflammation. The median bowel frequency decreased from 15x/24 h initially to 7x/24 h at 2 years. Continence was perfect in 24/37 cases. Twelve out of 37 cases had occasional nocturnal soiling and passive nocturnal fecal incontinence was reported by 2/37 patients. The neorectal compliance volume recovered from 12.5 ml kPa after subtotal colectomy and 11 ml/kPa at 6 months after INRA to a neorectal compliance of 24 ml/kPa at 2 years' follow-up (p < 0.002; Wilcoxon signed rank test)., Conclusion: The INRA procedure shows a low complication rate and reasonable functional results, there was however a considerable conversion rate in these first 53 cases and a high incidence of reclassification to CD., (Copyright 2004 S. Karger AG, Basel.)

The objective of this study is to investigate the effects of an acute necrotizing pancreatitis (ANP), without biliary obstruction, on the migrating motor complex (MMC), small bowel bacterial overgrowth (SBBO), bacterial translocation (BT) and infection of the pancreas simultaneously. Rats were divided into four groups: mild pancreatitis, control, ANP and sham operated control. Jejunal myoelectrodes were used to measure MMCs. Blood, peritoneal fluid, bile, and abdominal organs were harvested for microbial culturing 72 h after induction of pancreatitis. The splenic portion of the pancreas was taken for histology. During ANP the MMC cycle length was significantly increased from 14.1 +/- 0.2 to 22.4 +/- 1.9 min (P < 0.05). The duodenum of ANP rats was in contrast with the other groups characterized by Enterobacteriacae (> 3 log 10 CFU g-1 in seven of 12 rats, P < 0.05). A positive correlation (r = 0.78, P < 0.01) existed between duodenal Gram-negative and anaerobic flora and the MMC cycle. Correlation between MMC cycle length and BT to the pancreas was positive as well (r = 0.70, P < 0.01). A positive correlation (r = 0.85, P < 0.01) was found between the severity of pancreatitis and duodenal bacterial overgrowth. During ANP without biliary obstruction, the jejunal MMC is disturbed and consequently SBBO occurs. The correlation between the severity of pancreatitis, the disturbance of the MMC and SBBO suggests an important pathophysiological role of the proximal small bowel in the infection of pancreatic necrosis.

Transient lower esophageal sphincter relaxations (tLESRs) are vagally mediated in response to gastric cardiac distension. Nine volunteers, eight gastroesophageal reflux disease (GERD) patients, and eight fundoplication patients were studied. Manometry with an assembly that included a barostat bag was done for 1 h with and 1 h without barostat distension to 8 mmHg. Recordings were scored for tLESRs and barostat bag volume. Fundoplication patients had fewer tLESRs (0.4 +/- 0.3/h) than either normal subjects (2.4 +/- 0.5/h) or GERD patients (2.0 +/- 0.3/h). The tLESRs rate increased significantly in normal subjects (5.8 +/- 0.9/h) and GERD patients (5.4 +/- 0.8/h) during distension but not in the fundoplication group. All groups exhibited similar gastric accommodation (change in volume/change in pressure) in response to distension. Fundoplication patients exhibit a lower tLESR rate at rest and a marked attenuation of the response to gastric distension compared with either controls or GERD patients. Gastric accommodation was not impaired with fundoplication. This suggests that the receptive field for triggering tLESRs is contained within a wider field for elicitation of gastric receptive relaxation and that only the first is affected by fundoplication.

Motilin was infused in this study with the aim of examining refractory characteristics for motilin stimulation of antral phase III and fasting gallbladder emptying. Moreover, interdigestive pyloric and small intestinal motility from duodenum to ileum were studied, as these may be target organs for motilin. Eight fasting, healthy male volunteers received, on separate subsequent days, repeated infusions of 13leucine-motilin (8 pmol (kg min)(-1) for 5 min) or saline at 30 min after phase IIIs in the duodenum. Interdigestive motility of the antrum, pylorus, duodenum, jejunum and ileum was measured for maximum 10 h by using a 21-lumen perfused catheter. Gallbladder motility was measured by ultrasonography. Motilin infusions induced antral phase IIIs, but only after a preceding phase III of duodenal origin. Under this condition, time-interval to phase III at the duodenal recording site was 30 +/- 13 (SEM) min after motilin, compared with 79 +/- 14 min after saline (P < 0.01), and compared with 121 +/- 13 min for motilin infusion following an antral phase III (P < 0.001). Motilin did not affect small intestinal motility or isolated pyloric pressure waves (IPPWs). However, the number of IPPWs was significantly affected by the origin of the preceding phase III, irrespective of whether motilin or saline was infused. Gallbladder volume decreased significantly within 10 min after each motilin infusion. We conclude that this study clearly demonstrates differential regional effects of motilin. Motilin initiates antral phase IIIs, but stimulation is subject to a refractory period which is clearly prolonged after a preceding antral phase III. Motilin induced gallbladder emptying, however, is not subject to a refractory state. Small intestinal phase IIIs as well as pyloric IPPWs are not affected by motilin.

The aim of this study was to compare the effect of graded gastric barostat distension and meal-induced fundic relaxation on the elicitation of transient lower oesophageal sphincter relaxation (TLOSR). In 15 healthy subjects, stepwise fundic distension and oesophageal manometry were performed simultaneously. Next, the effect of meal ingestion on proximal stomach volume and lower oesophageal sphincter function was studied. During stepwise barostat distension of the proximal stomach, a significant linear correlation between intragastric pressure (r = 0.91; P < 0.01) and the TLOSR rate during inflation and subsequent deflation (r = 0.96; P < 0.01) was found. A similar relationship was found for volume. In addition, after meal ingestion, the TLOSR rate increased significantly from 1.40 +/- 3 to 5.4 +/- 1.5 h-1 (P < 0.01) and 5.2 +/- 1.7 h-1 (P < 0.01), respectively, during the first and second 30-min postprandially. However, at similar calculated intragastric volumes, barostat distension led to a significantly higher TLOSR rate than the meal. Similarly, distension-induced increase in gastric wall tension, estimated from the measured bag pressure and volume using Laplace's law, was associated with significantly higher TLOSR rates (P < 0.01). In conclusion, the rate of TLOSRs in healthy volunteers is directly related to the degree of proximal gastric distension and pressure-controlled barostat distension is a more potent trigger of TLOSRs than a meal. The latter finding suggests that tension receptor activation is an important stimulus for TLOSRs.

The purpose of this study was to develop a computer program for fully automated analysis of all presently known motor patterns in human colonic motility recordings. Colonic pressure recordings obtained from 24 healthy volunteers were used. Algorithms were developed for the detection and numerical analysis of five types of pressure waves: antegrade, retrograde, simultaneous, high-amplitude and isolated pressure waves. Furthermore, periodical motor activity was quantified. Validation was performed by comparison with visual analysis by two experienced observers. Patterns recorded during day- and night-time were compared using multiple-factor analysis of variance with Bonferroni correction. Automated analysis correlated well with visual peak detection (r = 0.98, P <0.01) and detection of antegrade pressure waves (r = 0.98, P <0.01). Most motor patterns showed a diurnal variation. During the night, prevalences of antegrade (938 vs 455; P <0.05), retrograde (112 vs 81; P <0.05), high-amplitude (12.9 vs 1.3; P <0.05), isolated pressure waves (1114 vs 765; P <0.05), and periodic motor activity were decreased (7.33 vs 4.47%; P <0.05). However, when expressed as percentage of absolute numbers of pressure waves, prevalences remained constant. In conclusion, fully automated analysis of all hitherto described colonic motility patterns is feasible. During the night, overall wave prevalences markedly decreased, but the distribution over the various motor patterns was preserved.

Background: Prucalopride is a selective and specific 5-hydroxytryptamine(4) receptor agonist that is known to increase stool frequency and to accelerate colonic transit., Aim: To investigate the effect of prucalopride on high-amplitude propagated contractions and segmental pressure waves in healthy volunteers., Methods: After 1 week of dosing (prucalopride or placebo in a double-blind, randomized, crossover fashion), colonic pressures were recorded in 10 healthy subjects using a solid-state pressure catheter with six sensors spaced 10 cm apart. Subjects kept diary records of their bowel habits (frequency, consistency and straining). High-amplitude propagated contractions were analysed visually, comparing their total numbers and using 10-min time windows. Segmental pressure waves were analysed using computer algorithms, quantifying the incidence, amplitude, duration and area under the curve of all detected peaks., Results: When taking prucalopride, stool frequency increased, consistency decreased and subjects strained less. Prucalopride just failed to increase the total number of high-amplitude propagated contractions (P=0.055). The number of 10-min time windows containing high-amplitude propagated contractions was increased by prucalopride (P=0.019). Prucalopride increased the area under the curve per 24 h (P=0.026)., Conclusions: The 5-hydroxytryptamine(4) receptor agonist prucalopride stimulates high-amplitude propagated contractions and increases segmental contractions, which is likely to be the underlying mechanism of its effect on bowel habits in healthy volunteers.

Quantitative analysis of myoelectric activity (EMG), to investigate small intestinal motility in rats, is normally based on manual classification into sequences of phase I, phase II and phase III. This classification is partly subjective. We aimed to develop a more objective method for the analysis of the migrating myoelectric complex (MMC). From the EMG, a derived signal is calculated as a measure of activity. Depending on the level of this derived signal, the EMG is classified into 'quiescent phase', 'irregular phase' or 'activity front'. The threshold levels for these phases are automatically calculated from the EMG data. A proposal for subdivision into MMCs is automatically generated. To calculate MMC length, the user must manually reject nonpropagated activity fronts. While developing the method, more than 19 derived signals were tested. These included variants of spike frequency, signal power and spike-burst length. The spike frequency signal was chosen because it gave minimal deviation from manual classification. Using the new automated method, recordings from the jejunum of 15 healthy rats were analysed (6 h each). The calculated phase lengths were consistent with the results of manual analysis. The presented method allows objective analysis of the interdigestive EMG signals of the small intestine.