A Multinational Comparison of Racecadotril and Loperamide in the Treatment of Acute Watery Diarrhoea in Adults

Background: Racecadotril (acetorphan) is an orally active, potent inhibitor of enkephalinase, which exerts an antihypersecretory effect without increasing intestinal transit time. The aim of this study was to compare the efficacy, safety and tolerability of racecadotril with those of loperamide by assessing their effects on the resolution of the signs and symptoms of diarrhoea in patients in developing countries who had acute watery diarrhoea of less than 5 days' duration. Methods: 945 outpatients from 21 centres in 14 countries received racecadotril (100 mg) or loperamide (2 mg) three times daily in a single-blind study. Duration of diarrhoea was the primary measure of efficacy; secondary criteria were overall clinical response, occurrence and duration of abdominal pain and distension, and occurrence of other associated signs and symptoms. Occurrence of constipation and adverse events were the main safety assessments. Results: Diarrhoea resolved rapidly with both racecadotril and loperamide (55.0 h in both groups), 92% of patients on racecadotril and 93% on loperamide being treatment successes. Racecadotril produced a significantly greater reduction in abdominal pain and distension than loperamide ( P = 0.024 and 0.03, respectively). The duration of abdominal distension was significantly shorter with racecadotril (5.4 versus 24.4 h; P = 0.0001), and constipation was also significantly less frequent (16% versus 25%; P = 0.001). One-hundred-and-eighty patients (19%) experienced one or more adverse event during the study: 67 (14.2%) in the racecadotril group and 113 (23.9%) in the loperamide group ( P = 0.001). Conclusions: Racecadotril resolved the symptoms of acute diarrhoea rapidly and effectively, and produced more rapid resolution of abdominal symptoms and less constipation than loperamide.     

A blind, randomized comparison of racecadotril and loperamide for stopping acute diarrhea in adults

AIM: Racecadotril is a specific enkephalinase inhibitor that exhibits intestinal antisecretory activity without affecting intestinal transit. Loperamide is an effective anti-diarrheal agent, but it usually induces constipation. This study is to compare the efficacy, safety, and tolerability of racecadotril versus loperamide in the outpatient treatment of acute diarrhea in adults. METHODS: A two-center, randomized, parallel-group, single-blind study was carried out to compare the efficacy, tolerability, and safety of racecadotril (100 mg thrics daily) and loperamide (2.0 mg 2 twics daily) in 62 adult patients suffering from acute diarrhea. The main efficacy criterion used was the duration of diarrhea after beginning the treatment (in hours). Other signs and symptoms were also evaluated. RESULTS: The clinical success rates for these anti-diarrheal treatments were 95.7% and 92.0% for racecadotril and loperamide respectively. Patients on racecadotril had a median duration of diarrhea of 19.5 h compared with a median of 13 h for patients on loperamide. Rapid improvement in anal burn and nausea was found for each drug. However, more patients on loperamide suffered from reactive constipation (29.0% vs 12.9%). Itching, another adverse event was notably higher in the racecadotril group (28.6% vs 0%). With regard to other adverse events, the two medications showed similar occurrence rates and similar concomitant medication usage rates. CONCLUSION: Racecadotril and loperamide are rapid, equally effective treatments for acute diarrhea in adults, but loperamide treatment is associated with a higher incidence of treatment-related constipation.     

Efficacy and tolerability of racecadotril in the treatment of cholera in adults: a double blind,randomised, controlled clinical trial

BACKGROUND: The enkephalins, endogenous opiate substances, act as neurotransmitters along the entire digestive tract where they elicit intestinal antisecretory activity without affecting intestinal transit time or motility. Racecadotril, through inhibition of enkephalinase, reinforces the physiological activity of endogenous enkephalins and, therefore, shows intestinal antisecretory activity. AIM: We conducted the study to determine the role of racecadotril as an adjunct to the standard treatment of cholera in adults. METHODS: The study was a double blind, randomised, placebo controlled clinical trial involving 110 adult male cholera patients who received either racecadotril or placebo in addition to standard cholera treatment. The major outcome measures (stool output, oral rehydration solution (ORS) intake, requirements for unscheduled intravenous fluid infusion, and duration of diarrhoea) were compared between the groups. RESULTS: Of 110 patients enrolled, 54 received racecadotril and 56 received placebo. Admission clinical characteristics were comparable between the groups. There was no significant difference in (mean (SD)) total stool output (racecadotril v placebo 315 (228) v 280 (156) g/kg), total ORS intake (390 (264) v 369 (240) ml/kg), or duration of diarrhoea (35 (15) v 32 (13) hours) between the groups. Clinical success, defined as resolution of diarrhoea within 72 hours of initiation of study intervention, was similar in both groups (racecadotril v placebo 96% v 89%). The number of patients receiving unscheduled intravenous infusions was not significantly different between the groups (racecadotril v placebo 22% v 14%). No drug related adverse effect was noted. CONCLUSION: The study demonstrated that racecadotril therapy, although found to be safe, does not provide additional benefit in the treatment of severe cholera in adults.     

Focus on acute diarrhoeal disease

Diarrhoea is an alteration of normal bowel movement characterized by an increase in the water content, volume, or frequency of stools. Diarrhoea needs to be classified according to the trends over time （acute or chronic） and to the characteristics of the stools （watery, fatty, inflammatory）. Secretory diarrhoeas, mostly acute and of viral aetiology in more than 70% of cases, are by far the most important subtype of diarrhoeas in terms of frequency, incidence and mortality （over 2.5 million deaths/year in developing countries）. Natural and synthetic opiates such as morphine, codeine, and Ioperamide which react with endogenous opiates （enkephalins, beta-endorphins, dynorphins） mainly act on intestinal motility and slow down transit. An antidiarrhoeal drug developed in recent years, racecadotril, acts as an enkephalinase inhibitor. Clinical studies have shown that it is just as effective as ioperamide in resolving acute diarrhoea but with greater reduction in pain and abdominal distension. Some studies have explored the prevalence of diarrhoea in old age. An epidemiological study carried out in Italy by 133 General Practitioners on 5515 elderly outpatients reported a prevalence of diarrhoea, defined according to the Rome criteria, of 9.1%. Infectious diseases （19%） and drug use （16%） were the most common causes of diarrhoea in old age. Regardless of the cause, the treatment of elderly patients with diarrhoea must include rehydration and nutritional support. Every year, more than 50 million tourists travel from industrialized countries to places where hygiene levels are pool. At least 75% of those travelling for short periods mention health problems, and in particular traveller＇s diarrhoea.     

Anorectal manometry in irritable bowel syndrome: differences between diarrhoea and constipation predominant subjects.

Anorectal manometry with balloon distension was performed on 28 patients with diarrhoea predominant irritable bowel syndrome, 27 patients with constipation predominant irritable bowel syndrome and 30 normal controls. In the diarrhoea predominant group balloon volumes required to perceive the sensations of gas, stool, urgency of defecation and discomfort were significantly lower than in controls or constipation predominant patients (p less than 0.001). Diarrhoea predominant patients also had a significantly lower rectal compliance than controls or constipation predominant patients (p less than 0.03) but showed no difference in motor activity induced by distension. When the constipation predominant patients were compared with controls the only significant difference that emerged was in the volume at which discomfort was perceived. No significant differences between constipated subjects and controls were found in the distension induced motor activity. Symptom severity and psychological parameters were also recorded and the diarrhoea predominant patients were found to be more anxious than those with constipation (p = 0.04). It proved possible (by comparison with the control group) to identify three abnormal rectal subtypes in patients with irritable bowel syndrome. These were a sensitive rectum (low sensation thresholds, normal or low rectal pressure), a stiff rectum (normal or low sensation thresholds, high pressure) and an insensitive rectum (high sensation thresholds, normal or high pressure) and their distribution varied considerably depending on bowel habit. Some form of rectal abnormality was identified in 75% of diarrhoea predominant patients compared with 30% of constipation predominant subjects (p = 0.002). A sensitive rectum was a particular feature of diarrhoea predominant patients being observed in 57% of patients compared with only 7% of the constipated group (p less than 0.001).     

Dysmotility of the small intestine in irritable bowel syndrome.

Though the pathophysiology of the irritable bowel syndrome (IBS) is commonly attributed to dysfunction of the large intestine, evidence exists to incriminate the small bowel. In order to further explore the role of the small bowel in IBS several stimuli were applied, in an attempt to unmask the dysmotility of the jejunum and ileum. These included infusions of cholecystokinin-octapeptide (CCK-OP), a high fat meal, neostigmine and balloon distension of the ileum. Three groups (n = 8) each of age and sex matched healthy volunteers were studied; patients with IBS complained of predominant constipation (n = 8) or diarrhoea (n = 8). Patients with IBS responded excessively to stimulation by CCK-OP, fatty meal, and ileal distension. In general patients with diarrhoea were more sensitive to stimuli than those with constipation. The ileum responded more to stimulation than the jejunum. As in the large bowel, stimuli appear to unmask intestinal dysmotility in patients with IBS. Motor abnormalities were often accompanied by abdominal symptoms, raising the possibility that dysfunction of the small bowel contributes to the symptoms of IBS.     

Hirschsprung's disease and its allied disorders in adults' histological and clinical studies

BACKGROUND/AIMS: To accurately diagnose for Hirschsprung's disease and its allied disorders in adults, we studied the histology and clinical future of 12 adult patients with prolonged, refractory constipation with abdominal distension and pain. METHODOLOGY: Based on clinical signs and symptoms noted on admission, all of 114 patients (12 males and 104 females, aged 20-74 years with a mean age of 56.6 years) were suspected to have refractory chronic constipation. To obtain an accurate diagnosis, we performed rectal biopsy. Tissue samples were frozen and 12-micron sections were stained with hematoxylin-eosin, with acetylcholinesterase by the method of Karnovsky and Roots, and with NADPH-diaphorase by the modified Scherer-Singler's method. RESULTS: 1) Histological examinations; On the basis of histological studies (rectal biopsies), 8 were diagnosed with hypoganglionosis, 2 with Hirschsprung's disease, and 2 with intestinal neuronal dysplasia. It was possible to diagnose Hirschsprung's disease and intestinal neuronal dysplasia using rectal mucosal biopsies with hematoxylin-eosin and acetylcholinesterase staining. However, accurate diagnosis of hypoganglionosis could be made only through examination of the myenteric plexus by NADPH-diaphorase staining in full-thickness rectal specimens. 2) Clinical symptoms; All patients had refractory chronic constipation with abdominal pain and distension. Two patients with Hirschsprung's disease had constipation neonatally. Of the 8 patients with hypoganglionosis, one had constipation neonatally at sucking age, 2 as infants, 2 at school age, and 2 after operation as adults. Two patients with intestinal neuronal dysplasia had constipation while infants. Onset of signs and symptoms before school age was significantly revealed than that found after operation as adults (P < 0.01). Frequency of bowel movements was 1/7-10 days for Hirschsprung's disease, 1/7-14 days for hypoganglionosis, and 1/7-30 days for intestinal neuronal dysplasia. CONCLUSIONS: We were able obtain accurate histological diagnosis of patients with Hirschsprung's disease and intestinal neuronal dysplasia by rectal mucosal biopsy with hematoxylin-eosin and acetylcholinesterase staining. Patients with hypoganglionosis obtained accurate histological diagnosis by full-thickness rectal biopsy with NADPH-diaphorase staining. Onset of symptoms of disease occurred predominantly before school age. In all of the patients, bowel movements occurred less than once per week.     

Differing coping mechanisms, stress level and anorectal physiology in patients with functional constipation

AIM: To investigate coping mechanisms, constipation symptoms and anorectal physiology in 80 constipated subjects and 18 controls. METHODS: Constipation was diagnosed by Rome Ⅱ criteria. Coping ability and anxiety/depression were assessed by validated questionnaires. Transit time and balloon distension test were performed. RESULTS: 34.5% patients were classified as slow transit type of constipation. The total colonic transit time (56 h vs 10 h, P<0.0001) and rectal sensation including urge sensation (79 mL vs 63 mL, P=0.019) and maximum tolerable volume (110 mL vs95 mL, P=0.03) differed in patients and controls. Constipated subjects had significantly higher anxiety and depression scores and lower SF36 scores in all categories. They also demonstrated higher scores of'monitoring'coping strategy (14±6 vs9±3, P=0.001), which correlated with the rectal distension sensation (P=0.005), urge sensation (P=0.002), and maximum tolerable volume (P=0.035). The less use of blunting strategy predicted slow transit constipation in both univariate (P=0.01) and multivariate analysis (P=0.03). CONCLUSION: Defective or ineffective use of coping strategies may be an important etiology in functional constipation and subsequently reflected in abnormal anorectal physiology.     

Extended analysis of a double-blind,placebo-controlled, 15-week study with otilonium bromide in irritable bowel syndrome

BACKGROUND/OBJECTIVE: In order to follow the most recent developments and recommendations in trial methodology for drug evaluation in patients with irritable bowel syndrome, we performed an extended analysis of a large clinical trial from a previously published study of otilonium bromide, using an assessment that integrates the key symptoms of irritable bowel syndrome. MATERIALS AND METHODS: A large-scale clinical trial with a double-blind, placebo-controlled, parallel-group study design was conducted in 378 patients, treated for 15 weeks with the recommended standard dose of 40 mg otilonium bromide or placebo three times daily. The study was based on the collection of 12 single efficacy endpoints. The new efficacy assessment was based on the data reported by the patients. Rather than demonstrating score differences between the treatment groups of the study, we carried out an assessment that integrates the most frequent symptoms reported (pain frequency and intensity, presence of meteorism and distension) by the patient. RESULTS: The rate of response to treatment within 2-4 months (the primary efficacy outcome measure) was significantly higher in the otilonium bromide group (36.9%) than in the placebo group (22.5%; P = 0.007). In each month of treatment, the rate of monthly response was higher in the otilonium bromide group as compared to the placebo group (P < 0.05). The total monthly and weekly responses to the single endpoints (intensity and frequency of pain and discomfort, meteorism/abdominal distension, severity of diarrhoea or constipation and mucus in the stool) were significantly more frequent in the group treated with otilonium bromide than in the placebo-treated group, with differences ranging from 10% to 20%. The subgroup analysis of the intestinal habits endpoint indicates that patients with diarrhoea have an additional benefit. CONCLUSION: The present re-evaluation of a previously published study confirms that otilonium bromide is more effective than placebo for the treatment of irritable bowel syndrome, being very efficient in relieving pain and discomfort.     

Racecadotril versus loperamide: antidiarrheal research revisited

Racecadotril is an enkephalinase inhibitor, presented as a purely antisecretory agent with advantages over the opiate-receptor agonist loperamide in the treatment of diarrhea. A critical review of the literature and the models used was performed. Although pretreatment with high doses of racecadotril reduced cholera toxin-induced secretion and although clinical efficacy was demonstrated in young infants—a population characterized by 10-fold higher plasma enkephalin concentrations compared with adults, the analysis calls into question the peripheral antisecretory selectivity and relative clinical efficacy. Conversely, loperamide can be proposed as an antisecretory agent at therapeutic concentrations. Its efficacy is well established in acute and chronic diarrhea. Current experimental and clinical comparative studies of both drugs have problems with regard to the selection of the doses, the validity of models, and/or the trial design. The conclusion is that more research is needed before reliable conclusions can be drawn on the place of racecadotril in diarrhea treatment.     

Sensation of bloating and visible abdominal distension in patients with irritable bowel syndrome

OBJECTIVES: Abdominal bloating and distension are common symptoms of irritable bowel syndrome (IBS). The postulated pathophysiological mechanisms underlying these symptoms include increased production, retention, or perception of gas or luminal contents. The aims of this study were to prospectively compare the prevalence of, and clinical factors related to, bloating and distension in an IBS patient population. METHODS: A total of 714 consecutive patients who met Rome I criteria for IBS were prospectively surveyed, and were classified as having bloating alone (B) or bloating and distension (B+D) based on a comprehensive bowel symptom questionnaire. GI, extraintestinal, and psychological symptoms, as well as health-related quality of life measures were also assessed using validated survey instruments. RESULTS: A total of 542 IBS patients (76%) who reported abdominal bloating were studied. Of these, 132 patients fulfilled criteria for the B group, whereas 410 patients fulfilled criteria for the B+D group. There was a significantly different gender distribution in the B and B+D groups (female:male ratios, 1.4:1 and 2.8:1, respectively p < 0.02). There was also a significantly different bowel habit subgroup distribution, with a greater predominance of constipation in B+D group and of diarrhea in the B group (p < 0.03). Both groups were similar in other clinical parameters, including progressive worsening of symptoms during the day, and relief by passing stool or gas. Both bloating and distension worsened when other abdominal symptoms worsened. Abdominal distension was associated with greater symptom severity and less diurnal variation in symptoms, and was less often perceived as associated with food intake. CONCLUSIONS: Bloating and visible abdominal distension may arise from two distinct but interrelated physiological processes. Although the sensation of bloating may be related to enhanced sensitivity to visceral afferent stimulation, abdominal distension in more severely affected patients may be related to triggering of a visceromotor reflex affecting the tone of abdominal wall muscles.     

Impact of bile acid malabsorption on steatorrhoea and symptoms in patients with chronic diarrhoea

OBJECTIVE: Bile acids are important for fat absorption. The relationship between bile acid malabsorption and steatorrhoea and gastrointestinal symptoms in patients with chronic diarrhoea has only been studied on a limited scale. DESIGN: Ninety-four patients referred for chronic diarrhoea were prospectively investigated with the 75SeHCAT test, a faecal fat excretion test and registration of symptoms in addition to the standard clinical work-up. METHODS: The correlation between the 75SeHCAT value and the faecal fat excretion was calculated for different groups of patients. Symptoms were registered in a questionnaire over a period of seven consecutive days. RESULTS: Forty-two patients had a 75SeHCAT value < 10%. Mild steatorrhoea was common in patients with non-organic bile acid malabsorption (50%) and in patients with functional diarrhoea (38%). There was no correlation between low 75SeHCAT values and steatorrhoea, although some patients with severe organic disease had a concomitant malabsorption of fat and of bile acids. In coeliac disease, severe steatorrhoea was common even in patients with high 75SeHCAT values. Patients with bile acid malabsorption had more frequent (P < 0.008) and looser (P= 0.0021) stools compared with patients with functional diarrhoea. There was no difference in abdominal pain, distension or flatulence. CONCLUSION: Mild steatorrhoea is common in both non-organic bile acid malabsorption and functional diarrhoea. The 75SeHCAT value cannot predict the risk of steatorrhoea. The high prevalence of bile acid malabsorption in patients with chronic diarrhoea and the absence of specific symptoms, except frequent and more liquid stools, indicates that the 75SeHCAT test should be performed early in the investigation of these patients.     

Chronic idiopathic intestinal pseudo-obstruction: clinical and intestinal manometric findings.

We report the clinical and intestinal manometric findings in a group of 42 patients with chronic idiopathic intestinal pseudo-obstruction evaluated at the Mayo Clinic. The main clinical manifestations in these patients were nausea and vomiting (83%), abdominal pain (74%), distension (57%), constipation (36%), diarrhoea (29%), and urinary symptoms (17%). These symptoms preceded surgery in all patients. Air fluid levels or distended bowel loops occurred in 57% and a dilated bladder or urinary excretory pathway in 17%. All patients showed intestinal manometric abnormalities none of which are seen in healthy individuals: aberrant configuration or propagation of interdigestive motor complexes in 25 patients; bursts (greater than 2 min duration) of non-propagated phasic pressure activity in fasting and/or fed state in 30 patients; sustained incoordinated fasting pressure activity in 15 patients; and inability of an ingested meal to convert fasting into fed pattern in 28 patients. We conclude that qualitative analysis of intestinal manometry provides evidence of gut dysmotility in patients with the clinical syndrome of chronic intestinal pseudo-obstruction. These abnormalities of motility can help to establish the correct diagnosis.     

匹维溴胺单用及联用黛力新治疗肠易激综合征的疗效观察

目的 观察匹维溴胺及匹维溴胺联用黛力新对肠易激综合征患者治疗的效果。方法 按罗马Ⅱ标准选择126例IBS随机分为两组,每组63例。仅予匹维溴胺治疗者为单剂组,同时予匹维溴胺和黛力新治疗者为联用组。单剂组口服匹维溴胺50mg,tid;联用组患者在单剂组的用药基础上加用黛力新,每日2片。结果 治疗2周后,单剂组和联用组的症状学评分均显著降低(P<0.05),联用组在便秘、腹痛、腹胀三项症状的改善上显著优于单用组(各为:0.52±0.20比1.63±0.16;0.74±0.20比1.42±0.20;0.69±0.11比1.37±0.44;P<0.05)。结论 匹维溴胺能够有效缓解IBS患者的症状;对于以便秘、腹痛、腹胀为主的IBS患者,加用黛力新可以得到更好的疗效。     

ARTHRITIS WITH SIGMOID VOLVULUS AND HL-A B27

A 43-year-old male developed seronegative polyarthritis aftera short attack of diarrhoea. For about two years before he hadexperienced intermittent abdominal pain, distension and constipation.Laparotomy showed a chronic sigmoid volvulus for which sigmoidcolectomy was performed. Post-operatively he had no furtherbowel symptoms, no further arthritis and there was radiologicalimprovement of involved joints. Tissue typing showed HL-A B27antigen.     

Presenting clinical features and C-reactive protein in the prediction of a positive stool culture in patients with diarrhoea

OBJECTIVES: To devise a scoring system by which clinical features and C-reactive protein (CRP) can be used to predict a positive stool culture in patients admitted with acute diarrhoea. METHODS: One hundred and thirty-two patients admitted to the Regional Infection Unit with diarrhoea thought to be due to bacterial gastroenteritis were included. Clinical features, CRP and outcome of stool culture were recorded, together with the final diagnosis. RESULTS: Forty-one patients had bacterial gastroenteritis characterized by the isolation of a bacterial enteropath (BGE). Sixty-three patients had non-specific gastroenteritis, defined as more than three loose stools per day with no bacterial enteropath isolated (NSGE). In 28 patients another diagnosis was made (Others). More of the patients with BGE (91%) had abdominal pain as compared with those with NSGE (67%) and Others (61%) (P=0.01). The mean duration of symptoms was longer in the Others group (6.14 days) as compared with patients with BGE (3.29) and NSGE (3.25) (P=0.01). The mean CRP was significantly higher in those with BGE (113.9mg/l) and Others (116.9mg/l) as compared to the NSGE patients (38.9mg/l) (P=0.001). A scoring system was devised which incorporated the presence or absence of abdominal pain (+10 or 0), the duration of symptoms (-10, for 5 or more days, 0 for less than 5 days of symptoms) and the CRP (CRP<50=0, CRP>50=5). A score of 15 or more predicted 79% of patients with BGE, while a score of <15 predicted 87% of those with NSGE and 86% of those with another diagnosis. CONCLUSIONS: This simple scoring system may be useful in predicting the positivity of stool culture, and therefore may be helpful in targeting those small number of patients who require antimicrobial therapy after hospital admission. We would not, however, favour reliance on this scoring system alone to choose whom to treat with antimicrobials.     

Rectal afferent hypersensitivity and compliance in irritable bowel syndrome: differences between diarrhoea-predominant and constipation-predominant subgroups

OBJECTIVES: To evaluate the differences in rectal compliance and sensory thresholds for the urge to defecate and discomfort between irritable bowel syndrome (IBS) subgroups and controls, and to correlate these parameters with rectal symptoms. METHODS: A total of 38 IBS patients [Rome II criteria; 19 diarrhoea-predominant IBS (D-IBS), 16 constipation-predominant IBS (C-IBS), three with alternating diarrhoea and constipation IBS (Alt-IBS)] and 10 controls were studied. A barostat was used to measure rectal compliance and sensory thresholds, in the 'unprepared' rectum. The thresholds for the urge to defecate and discomfort were determined using phasic rectal balloon distension in a double random staircase sequence. RESULTS: D-IBS had significantly lower rectal compliance and threshold for the urge to defecate compared with controls [4 ml/mmHg interquartile range (IQR) 3.99 versus 8.4 ml/mmHg IQR 5.69; P=0.001; 8 mmHg IQR 6 versus 20 mmHg IQR 4; P=0.003]. D-IBS also had significantly lower rectal compliance and threshold for the urge to defecate compared with the C-IBS group (5.8 ml/mmHg IQR 4.61; P=0.027; 16 mmHg IQR 12; P=0.003). The volume at the threshold for discomfort was significantly lower in D-IBS compared with controls (163 ml IQR 99.5 versus 212 ml IQR 147.25; P=0.016). The severity of abdominal pain and rectal symptoms showed a significantly negative correlation with rectal sensory thresholds. CONCLUSION: This study shows that the sensory threshold for the urge to defecate and rectal compliance is significantly lower in D-IBS compared with C-IBS and controls. The consequent inability to tolerate rectal faecal loading may account for the symptoms of the passage of frequent, small-volume stools in D-IBS patients.     

Irritable bowel syndrome: relationship of disorders in the transit of a single solid meal to symptom patterns.

The time taken for a solid meal to pass through the stomach, small intestine, and colon was measured in 61 patients with irritable bowel syndrome, subdivided according to their presenting symptoms, and in 53 healthy volunteers. Small bowel transit times were significantly shorter in patients who complained predominantly of diarrhoea (3.3 +/- 0.3 vs 4.2 +/- 0.2 h; p = 0.01; n = 21) and significantly longer in patients who complained predominantly of constipation (5.4 +/- 0.3 vs 4.2 +/- 0.2 h; p less than 0.01; n = 23) or pain and distension (5.4 +/- 0.4 vs 4.2 +/- 0.2 h; p less than 0.01; n = 17) compared with controls. Whole gut transit times were shorter in patients who complained of diarrhoea (35 +/- 5 vs 53 +/- 4 h; p less than 0.01), and longer in patients with constipation (87 +/- 13 vs 53 +/- 4 h; p less than 0.05) compared with controls. No significant differences in gastric emptying rates were shown between any of the patient groups and normal controls. Thirty-four patients reported pain, particularly in the right iliac fossa, during the meal transit test, and in 25 of these (74%), the onset of the pain was associated with the arrival of residues of the test meal in the caecum. Our results indicate that irritable bowel syndrome should be considered a disease of the small intestine as well as the colon.     

Efficacy and tolerability of racecadotril in acute diarrhea in children

BACKGROUND & AIMS: Oral rehydration therapy is the only treatment recommended by the World Health Organization in acute diarrhea in children. Antisecretory drugs available could not be used because of their side effects, except for racecadotril, which is efficient in acute diarrhea in adults. METHODS: The efficacy and tolerability of racecadotril (1.5 mg/kg administered orally 3 times daily) as adjuvant therapy to oral rehydration were compared with those of placebo in 172 infants aged 3 months to 4 years (mean age, 12.8 months) who had acute diarrhea. The treatment groups were comparable in terms of age, duration of diarrhea, number of stools, and causative microorganism at inclusion. RESULTS: During the first 48 hours of treatment, patients receiving racecadotril had a significantly lower stool output (grams per hour) than those receiving placebo. The 95% confidence interval was 43%-88% for the full data set (n = 166; P = 0.009) and 33%-75% for the per-protocol population (n = 116; P = 0.001). There was no difference between treatments depending on rotavirus status. Significant differences between treatment groups were also found after 24 hours of treatment: full data set (n = 167; P = 0.026) and per-protocol population (n = 121; P = 0.015). Tolerability was good in both groups of patients. CONCLUSIONS: This study demonstrates the efficacy (up to 50% reduction in stool output) and tolerability of racecadotril as adjuvant therapy to oral rehydration solution in the treatment of severe diarrhea in infants and children.     

Lactose malabsorption in Greek adults: correlation of small bowel transit time with the severity of lactose intolerance.

Using breath hydrogen analysis after 139 mmol (50 g) oral lactose load, we investigated the prevalence of lactose malabsorption in 200 Greek adults and examined the relationship between symptoms and small bowel transit time. One hundred and fifty subjects had increased breath hydrogen concentrations (greater than 20 ppm) after the lactose load. In these individuals peak breath hydrogen concentration was inversely related to small bowel transit time (r = 0.63, 6 = 6.854, p less than 0.001) and the severity of symptoms decreased with increasing small bowel transit time. Lactose malabsorbers with diarrhoea during the lactose tolerance test had a small bowel transit time of 51 +/- 22 minutes (x +/- SD; n = 90) which was significantly shorter than the small bowel transit time of patients with colicky pain, flatulence, and abdominal distension (74 +/- 30, n = 53; p less than 0.001) and both groups had significantly shorter small bowel transit time than that of asymptomatic malabsorbers (115 +/- 21 n:7; p less than 0.001). When the oral lactose load was reduced to 33 mmol (12 g), the small bowel transit time increased five-fold and the overall incidence of diarrhoea and/or symptoms decreased dramatically. These results indicate that the prevalence of lactase deficiency in Greece may be as high as 75% and suggest that symptom production in lactose malabsorbers is brought about by the rapid passage down the small intestine of the malabsorbed lactose.