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PubMed1992

Treatment of opioid-induced constipation with oral naloxone: a pilot study.

Opioids cause constipation by binding to specific opioid receptors in the enteric and central nervous systems. First-pass glucuronidation limits systemic bioavailability of oral naloxone. This study was designed to determine if oral naloxone could reverse opioid-induced constipation without precipitating abstinence or recrudescence of pain in opioid-dependent individuals. Concentrations of unmetabolized and total naloxone, including naloxone glucuronide, were measured by radioimmunoassay. A dose-related increase in symptoms of laxation resulted in all three opioid-dependent patients studied that paralleled the increase in active and total naloxone plasma levels. Withdrawal symptoms occurred with plasma naloxone area under the plasma concentration-time curves above 550 ng.min/ml and with dosing intervals less than 3 hours. Peak plasma levels did not predict withdrawal. Oral naloxone ameliorates opioid-induced constipation in opioid-dependent persons. Titration of dose to a maximum of 12 mg at least 6 hours apart may be needed to avoid adverse reactions.

Adult↗
PubMed2006

A combination of fibre-rich rye bread and yoghurt containing Lactobacillus GG improves bowel function in women with self-reported constipation.

OBJECTIVE: The aim of the study was to investigate the effects of fibre-rich rye bread and yoghurt containing Lactobacillus GG (LGG) on intestinal transit time and bowel function, and to test whether they have an interaction in cases of self-reported constipation. DESIGN: The study was carried out as a two-by-two factorial design. SETTING: Free-living subjects. SUBJECTS: A total of 59 healthy women with self-reported constipation, recruited by advertisement. INTERVENTIONS: After a baseline period, the subjects were randomized into four diet groups: (1) rye bread+LGG yoghurt, (2) rye bread, (3) LGG yoghurt, and (4) control. The 3-week dietary intervention was followed by a 3-week follow-up period. During each period, total intestinal transit time was measured and the subjects recorded faecal frequency and consistency, difficulty in defecation and gastrointestinal symptoms. RESULTS: The rye bread shortened total intestinal transit time (mean difference, -0.7; CI(95), -1.1 to -0.2; P=0.007), increased faecal frequency (0.3; CI(95), 0.1 to 0.5; P=0.001), softened faeces (-0.3; CI(95), -0.4 to -0.2; P<0.001) and made defecation easier (-0.4; CI(95), -0.5 to -0.2; P<0.001), but also increased gastrointestinal symptoms (1.6; CI(95), 0.7 to 2.4; P<0.001) compared to the low-fibre toast consumed in the LGG and control groups. There were fewer symptoms in the rye bread+LGG group compared to the rye bread group (-1.3; CI(95), -2.4 to -0.2; P=0.027). CONCLUSIONS: Fibre-rich rye bread can be recommended in the treatment of constipation, and the simultaneous consumption of LGG yoghurt relieves the adverse gastrointestinal effects associated with increased intake of fibre. SPONSORSHIP: Valio Ltd, R&D, and Fazer Bakeries Ltd.

Abdominal Pain↗
PubMed1997

Sequential treatment of chronic constipation in paraplegic subjects.

Chronic constipation is the main gastrointestinal complaint of spinal cord injury (SCI) patients, and has a significant effect on patients' lives, concerning nursing dependence, morbidity and complications. Many therapies have been proposed to treat chronic severe constipation, most of them with limited effect or being unpredictable in their effect or being expensive or very radical. Ten spinal cord injury patients have been submitted to a therapeutic protocol based on a high residue diet, a standardised water intake, and on the use of a sequential schedule of evacuating stimuli. After four weeks of treatment the patients showed an increased frequency of bowel movements per week, a decreased total gastrointestinal transit time, and a decreased need for oral and rectal laxatives. This treatment seems to be effective in modifying patients' bowel habits, and therefore could be considered as a standardised protocol for the management of severe constipation in those who are paraplegic.

Adult↗
PubMed1997

Misoprostol in the treatment of chronic refractory constipation: results of a long-term open label trial.

BACKGROUND: Misoprostol is known to be effective in stimulating intestinal transit both in healthy individuals and in patients with chronic constipation when evaluated in short-term trials. The aim of this study was to determine the utility of misoprostol in the long-term management of patients with chronic refractory constipation. METHODS: Eighteen patients were offered misoprostol (600-2400 microg/day) as adjunctive therapy in an open-ended, non-blinded trial. All patients were encouraged to continue the drug for a minimum of 4 weeks, after which time the effect on bowel movement patterns was evaluated and continued use of misoprostol was offered to those patients who demonstrated a clinical benefit. RESULTS: Six patients withdrew prior to 4 weeks because of side-effects. In the 12 patients who continued the treatment and were evaluated at 4 weeks, the mean interval between bowel movement frequency had decreased from a baseline of 11.25 to 4.8 days (P = 0.0004). Eight patients continued the long-term treatment, with sustained response seen in six. In a subset of patients (n = 4) the effect of single-dose misoprostol (400 microg) was evaluated compared to healthy controls (n = 5) on post-prandial segmental colonic motility. Misoprostol augmented the colonic motility response to a meal throughout the colon, and this was significantly greater in the left versus right colonic segments (P < 0.05). CONCLUSIONS: Misoprostol can be effective as part of the long-term medical treatment of patients with chronic refractory constipation, but side-effects are observed at higher doses and can be a limiting factor. Part of misoprostol's action may be mediated through the augmentation of colonic motility, particularly of the left colon.

Adult↗
PubMed1997

Double-blind study of the effect of cisapride on constipation and abdominal discomfort as components of the irritable bowel syndrome.

AIM: To study the effect of prokinetic treatment with cisapride in patients with constipation-predominant irritable bowel syndrome. PATIENTS AND METHODS: Ninety-six patients were randomly assigned to treatment with either cisapride 5 mg three times daily or placebo three times daily for a period of 12 weeks. The dosage could be doubled after 4 weeks. Presence of the target symptoms abdominal pain, constipation and abdominal bloating was an obligatory criterion for inclusion in the study. RESULTS: After 12 weeks of treatment, 31%, 56% and 27% of the cisapride treated patients were found to be without the three target symptoms (P < 0.05). The corresponding percentages for the placebo-treated patients were 31%, 58% and 19%, respectively, (P < 0.05). The visual analogue scale (VAS) symptom scores assessed by the patients for global rating of bowel disease, general well-being and frequency of stool passage improved significantly within each treatment group (P < 0.05). Evaluation of efficacy parameters using intention-to-treat analysis showed no statistically significant differences between the groups. Using efficacy analysis, the difficulty of stool passage showed a significantly higher improvement with cisapride (P < or = 0.05). CONCLUSIONS: These results indicate that cisapride is not superior to placebo in the treatment of constipation and abdominal discomfort as components of irritable bowel syndrome. It may, however, be of use in improving the difficulty of stool passage.

Abdominal Pain↗
PubMed2001

Review article: the therapy of constipation.

Constipation is a common symptom that may be idiopathic or due to various identifiable disease processes. Laxatives are agents that add bulk to intestinal contents, that retain water within the bowel lumen by virtue of osmotic effects, or that stimulate intestinal secretion or motility, thereby increasing the frequency and ease of defecation. Drugs which improve constipation by stimulating gastrointestinal motility by direct actions on the enteric nervous system are under development. Other modalities used to treat constipation include biofeedback and surgery. Laxatives and lavage solutions are also used for colon preparation and evacuation of the bowels after toxic ingestions.

Biofeedback, Psychology↗
PubMed2002

Effects of prucalopride on colonic transit, anorectal function and bowel habits in patients with chronic constipation.

BACKGROUND: There is a need for better tolerated drugs to normalize bowel function in chronic constipation. Prucalopride is a highly selective, specific, serotonin4 receptor agonist with enterokinetic properties. AIM: To evaluate the effects of prucalopride on bowel function, colonic transit and anorectal function in patients with chronic constipation. METHODS: Twenty-eight patients were enrolled in this double-blind, placebo-controlled, crossover study (prucalopride: 1 mg, n=12; 2 mg, n=16). Patients kept a bowel function diary. Colonic transit times and anorectal function (anal manometry, rectal sensitivity and rectal compliance) were assessed. RESULTS: Prucalopride (1 mg) compared to placebo significantly increased the mean number of spontaneous complete, spontaneous and all bowel movements per week. Prucalopride (1 mg) significantly decreased the percentage of bowel movements with hard/lumpy stools and straining and increased the urge to defecate. Prucalopride (1 and 2 mg) decreased the mean total colonic transit time by 12.0 h (prucalopride 42.8 h vs. placebo 54.8 h; P=0.074). No statistically significant effects were found in any of the anorectal function parameters. Prucalopride was well tolerated. There were no clinically relevant changes in standard safety parameters. CONCLUSIONS: Prucalopride significantly improves stool frequency and consistency, and the urge to defecate, and may decrease colonic transit times in patients with chronic constipation.

Adolescent↗
PubMed2002

Prucalopride, a systemic enterokinetic, for the treatment of constipation.

BACKGROUND: Laxatives are frequently ineffective in treating constipation. An alternative therapeutic approach is to target serotonin-4 receptors, which are involved in initiating peristalsis. AIM: In a double-blind, placebo-controlled trial, to assess the efficacy and safety of a systemically active serotonin-4 agonist, prucalopride. METHODS: Seventy-four women with constipation were stratified into slow or normal transit groups, and each group was randomized to receive either placebo or 1 mg prucalopride daily for 4 weeks. A bowel function diary was maintained. Whole-gut and orocaecal transit, visceral sensitivity, quality of life and psychological state were assessed before and after treatment. RESULTS: Prucalopride, not placebo, increased spontaneous stool frequency (P=0.008) and reduced time to first stool (P < 0.001). Prucalopride reduced the number of retained markers in all patients compared to placebo (P=0.004). Prucalopride reduced the mean number of retained markers in slow transit (P=0.069), but did not alter the marker count in normal transit (P=0.86). Orocaecal transit was accelerated by prucalopride, not placebo (P=0.004). Prucalopride, notplacebo, increased rectal sensitivity to distension (urge volume, P=0.01) and electrical stimulation (P=0.001). Prucalopride significantly improved several domains of the Short Form Health Status Survey and the disease-specific quality of life. Adverse effects were similar for prucalopride and placebo. CONCLUSIONS: Prucalopride improves symptoms, upper gut transit and gut sensitivity in constipated patients with both slow and normal transit. It improves transit in patients with slow transit. These changes are associated with improved well-being.

Adult↗
PubMed1999

Identification of patients likely to benefit from biofeedback for outlet obstruction constipation.

BACKGROUND: Biofeedback for outlet obstruction constipation has a varying success rate. The aim of this study was to identify which patients are likely to respond to biofeedback. METHODS: Thirty patients with severe outlet obstruction constipation were treated by a specialist nurse using three or four sessions of visual and auditory feedback of anal sphincter pressures. All patients were assessed by evacuating proctography, whole-gut transit studies and anorectal physiology before treatment. RESULTS: Two patients did not complete the course of biofeedback. Nine patients improved. Before treatment these patients had predominantly normal anorectal physiology and were all able to open the anorectal angle at evacuating proctography. Nineteen patients did not improve, of whom only three had no measured abnormality other than inability to empty the rectum. Ten of these patients had abnormal anorectal physiology which may have been due to previous vaginal delivery. CONCLUSION: Biofeedback for outlet obstruction constipation is more likely to be successful in patients without evidence of severe pelvic floor damage.

Adolescent↗
PubMed1999

Comparative study of two sites of colonic conduit placement in the treatment of constipation due to rectal evacuatory disorders.

BACKGROUND: Chronic constipation may be treated by antegrade colonic irrigation via a colonic conduit. METHODS: Two alternative sites of colonic conduit construction were evaluated for their effect on the symptoms of 21 consecutive women with intractable constipation primarily due to rectal evacuatory disorders. The conduit was constructed in the sigmoid colon in the first 11 patients and in the transverse colon in the subsequent ten. Symptomatic outcome was evaluated clinically and by questionnaires, with a prospective quality of life assessment in the transverse group. RESULTS: During a median follow-up of 12 (range 6-60) months, reflux or stenosis necessitated revision or dilatation in six patients. Irrigation with a median of 1.3 (0.8-2.0) litres of water achieved evacuation in all patients. Improvements in abdominal pain and bloating were reported by seven of the ten patients in the transverse conduit group, but benefit was found in only three of 11 in the sigmoid group. There was no significant improvement in quality of life scores. In the medium term, seven patients retained a transverse conduit compared with three with a sigmoid conduit. CONCLUSION: The transverse colonic conduit offers better relief from the symptoms of constipation due to rectal evacuatory dysfunction than the sigmoid conduit.

Abdominal Pain↗
PubMed2000

Prolonged ambulatory recording of antroduodenal motility in slow-transit constipation.

BACKGROUND: Slow-transit constipation may be part of a pan-enteric motor disorder. To test this hypothesis 24-h ambulatory antroduodenal manometry was performed and orocaecal transit time determined in patients with slow-transit constipation and in healthy controls. METHODS: Antroduodenal motility was recorded with a five-channel solid-state catheter. Postprandial motility was recorded after consumption of two standardized test meals and interdigestive motility was recorded nocturnally. Manometry tracings were analysed for quantitative and qualitative abnormalities. Orocaecal transit time was determined by means of the lactulose hydrogen breath test. RESULTS: Postprandial motility was no different between patients and controls. However, some minor changes of interdigestive motility were observed. The proportion of phase II activity of the nocturnal cycles of the interdigestive migrating motor complex was increased in patients while phase I activity was decreased. The total number of observed phase III fronts was no different in patients and controls, although the number of phase III fronts with antral onset was decreased. Furthermore, the amplitude of phase III activity of duodenal onset was also decreased. Specific motor abnormalities such as retrograde propagation of phase III fronts were more frequent in patients. Orocaecal transit time was delayed in patients. CONCLUSION: In patients with slow-transit constipation, orocaecal transit time is delayed but antro- duodenal motility is generally well preserved with only minor alterations. Presented as a poster to the Digestive Disease Week meeting in New Orleans, Louisiana, USA, May 1998, and published in abstract form as Gastroenterology 1998; 114: A820

Adolescent↗
PubMed1999

Evaluation of a constipation risk assessment scale.

This project was undertaken in order to evaluate the utility of a constipation risk assessment scale and the accompanying bowel management protocol. The risk assessment scale was primarily introduced to teach and guide staff in managing constipation when caring for patients. The intention of the project was to reduce the incidence of constipation in patients during their admission to hospital.

Constipation↗
PubMed1997

The treatment of chronic constipation in adults. A systematic review.

OBJECTIVE: To evaluate whether laxatives and fiber therapies improve symptoms and bowel movement frequency in adults with chronic constipation. DATA SOURCES: English language studies were identified from computerized MEDLINE (1966-1995). Biological Abstracts (1990-1995), and Micromedex searches; bibliographies; textbooks; laxative manufactures; and experts. STUDY SELECTION: Randomized trials of laxative or fiber therapies lasting more than 1 week that evaluated clinical outcomes in adults with chronic constipation. MEASUREMENTS AND MAIN RESULTS: Two independent reviewers appraised each trial's characteristics including methodologic quality. There were 36 trials involving 1,815 persons from a variety of settings including clinics, hospitals and nursing homes. Twenty-three trials were 1 month or less in duration. Several laxative and fiber preparations were evaluated. Twenty trials had a placebo, usual care, or discontinuation of laxative control group, and 16 directly compared different agents. Laxatives and fiber increased bowel movement frequency by an overall weighted average of 1.4 (95% confidence interval [CI] 1.1-1.8) bowel movements per week. Fiber and bulk laxatives decreased abdominal pain and improved stool consistency compared with placebo. Most nonbulk laxative data concerning abdominal pain and stool consistency were inconclusive, though cisapride, lactulose, and lactitol improved consistency. Data concerning superiority of various treatments were inconclusive. No severe side effects for any of the therapies were reported. CONCLUSIONS: Both fiber and laxatives modestly improved bowel movement frequency in adults with chronic constipation. There was inadequate evidence to establish whether fiber was superior to laxatives or one laxative class was superior to another.

Adult↗
PubMed2001

Constipation as a cause of scrotal pain in children.

Six boys with scrotal pain and constipation were seen at our hospital within the past 5 years. All boys had no clinical findings of structural or infectious derangements, and experienced relief of testicular symptoms after evacuation of the fecal mass. The association between constipation and scrotal pain has not been previously reported, and may represent direct neural stimulation or chronic inflammation of testicular structures in patients with dysfunctional voiding. Recognition of the association between constipation and subacute or chronic scrotal pain can guide the clinician towards appropriate therapy for these patients.

Abdominal Pain↗
PubMed2002

Infantile cystinosis presenting as chronic constipation.

An infant presented with persistent constipation as the first clinical symptom of cystinosis before evidence of renal Fanconi's syndrome. The history of muscle weakness, failure to thrive, polydipsia, and polyuria prompted subsequent clinical and laboratory evaluations, leading to the correct diagnosis of cystinosis. Primary and persistent constipation as an initial manifestation of cystinosis has not been reported previously. Although rare, cystinosis should be considered in the differential diagnosis of constipation if other suggestive signs or symptoms are present.

Chronic Disease↗
PubMed2001

Prucalopride accelerates gastrointestinal and colonic transit in patients with constipation without a rectal evacuation disorder.

BACKGROUND & AIMS: Prucalopride (PRU) is a selective benzofuran 5-hydroxytryptamine(4)-receptor agonist with gastrointestinal and colonic prokinetic activities. We evaluated the effects of PRU on gastrointestinal and colonic transit in patients with constipation. METHODS: Gastrointestinal and colonic transit were measured over 48 hours in 40 patients who fulfilled modified Rome I criteria for functional constipation. Patients had no evidence of a rectal evacuation disorder. Subjects were randomized to receive a daily dose of 2 or 4 mg PRU or placebo in a double-blind, parallel-group design. Each treatment lasted 7 days. The transit test was performed over the last 48 hours of the study. Effects on gastric emptying, small bowel transit, and colonic transit were analyzed using Kruskal-Wallis and Wilcoxon rank sum tests. RESULTS: Of 61 patients screened, 40 were eligible and randomized. Two patients withdrew because of adverse events. PRU accelerated overall gastric emptying and small bowel transit. PRU tended to accelerate overall colonic transit with significantly faster overall colonic transit and ascending colon emptying with the 4-mg dose. CONCLUSIONS: PRU accelerates transit through the stomach, small bowel, and colon in patients with constipation unassociated with a rectal evacuation disorder.

Adult↗
PubMed2002

Enteric nerves and interstitial cells of Cajal are altered in patients with slow-transit constipation and megacolon.

BACKGROUND & AIMS: A variety of gastrointestinal motility disorders have been attributed to alterations of interstitial cells of Cajal and malformations of the enteric nervous system. This study evaluates both the distribution of interstitial cells of Cajal and the pathohistology of the enteric nervous system in 2 severe human colorectal motility disorders. METHODS: Colonic specimens obtained from patients with slow-transit constipation (n = 11), patients with megacolon (n = 6), and a control group (n = 13, nonobstructing neoplasia) were stained with antibodies against c-kit (marker for interstitial cells of Cajal) and protein gene product 9.5 (neuronal marker). The morphometric analysis of interstitial cells of Cajal included the separate registration of the number and process length within the different regions of the muscularis propria. The structural architecture of the enteric nervous system was assessed on microdissected whole-mount preparations. RESULTS: In patients with slow-transit constipation, the number of interstitial cells of Cajal was significantly decreased in all layers except the outer longitudinal muscle layer. The myenteric plexus showed a reduced ganglionic density and size (moderate hypoganglionosis) compared with the control group. Patients with megacolon were characterized by a substantial decrease in both the number and the process length of interstitial cells of Cajal. The myenteric plexus exhibited either complete aganglionosis or severe hypoganglionosis. CONCLUSIONS: The enteric nervous system and interstitial cells of Cajal are altered concomitantly in slow-transit constipation and megacolon and may play a crucial role in the pathophysiology of colorectal motility disorders.

Adult↗
PubMed2005

Biofeedback benefits only patients with outlet dysfunction, not patients with isolated slow transit constipation.

BACKGROUND & AIMS: Biofeedback is reported to be as effective for slow transit constipation as for pelvic floor dyssynergia and no more effective than education. We aimed to test the hypothesis that biofeedback benefits only patients with pelvic floor dyssynergia, describe the physiologic mechanism of treatment, and identify predictors of success. METHODS: Fifty-two patients (49 women; average age, 35 years), all with delayed whole gut transit, included 34 with pelvic floor dyssynergia, 12 with slow transit only, and 6 who met only 1 of 2 criteria for pelvic floor dyssynergia. All received 5 weekly biofeedback sessions directed at increasing rectal pressure and relaxing pelvic floor muscles during straining plus practice defecating a balloon. Patients were retested by questionnaire; symptom diary; balloon defecation; transit study at 1, 6, 12, and 24 months; and anorectal manometry at 1 and 6 months. RESULTS: At 6 months, greater improvements were seen in pelvic floor dyssynergia compared with slow transit only; 71% versus 8% reported satisfaction ( P = .001), and 76% versus 8% reported >/=3 bowel movements per week ( P < .001). Improvements were maintained at 24 months of follow-up. Biofeedback eliminated dyssynergia in 91% and enabled 85% to defecate the balloon. Satisfaction was correlated with improved ability to defecate the balloon (rho = .73; P < .001), reductions in dyssynergia (rho = .69; P < .001), and increased rectal pressure during straining (rho = .36; P < .01). Success was predicted by pelvic floor dyssynergia, milder constipation, and less frequent abdominal pain at baseline. CONCLUSIONS: Biofeedback is an effective treatment for pelvic floor dyssynergia but not slow transit constipation.

Abdominal Pain↗