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PubMed2002

Evaluation of myenteric ganglion cells and interstitial cells of Cajal in patients with chronic idiopathic constipation.

BACKGROUND AND AIMS: The aim of this study was to identify myenteric ganglion cells (MGC) and interstitial cells of Cajal (ICC) from the total colectomy specimen in patients with chronic idiopathic constipation. PATIENTS AND METHODS: Fourteen patients who had severe, intractable, long-standing (mean: 14 years) constipation underwent subtotal colectomy and ileorectal anastomosis. All resected specimens were investigated with hematoxylin and eosin (H&E) and immunohistochemical staining with anti-neurofilament monoclonal antibody NF(2)F(11) for MGC, and c-kit antibody for ICC. The numbers of MGC and ICC were counted for ascending (AC), descending (DC), and sigmoid colon (SC). We compared these data with those from ten control specimens. RESULTS: The number of MGC was significantly smaller in AC and DC of the constipated group than in the control group. Interestingly, SC contained a similar number of MGC. The two staining methods were equally effective for identifying MGC. The total ICC number in the constipated group was markedly lower in every segment. Most anatomical layers of the colon, including the submucosal border, circular muscle, and longitudinal muscle, revealed a similar tendency. However, in the myenteric plexus area there was no significant difference between the two groups. CONCLUSION: A quantitative decrease in MGC and ICC appears to be implicated in chronic idiopathic constipation.

Adult↗
PubMed2005

Slow transit colon constipation is not related to the number of interstitial cells of Cajal.

BACKGROUND AND AIMS: Recent studies have demonstrated decreased numbers of interstitial cells of Cajal in patients suffering from severe chronic constipation as measured by c-Kit (CD117) and CD34 immunohistology. In this study, we wished to determine whether there were abnormalities in the number of neurons of the Auerbach's plexus, their CD117 and CD34 immunoreactivity, or the thickness of colon wall sections in patients with refractory slow transit colonic constipation as compared with control subjects. PATIENTS AND METHODS: Specimens from 13 patients who had undergone subtotal colectomy for severe chronic constipation refractory to medical treatment were compared with normal controls. Enteric neurons of Auerbach's plexus were counted, and thickness of the circular and longitudinal layer of the muscularis externa as well as total muscularis externa was measured. Quantitative assessment of anti-CD117 and anti-CD34 immunoreactivity was performed using an Automated Cellular Imaging System and expressed as fractional scores. RESULTS: Except for a decreased circular muscle layer thickness in the constipated patients, no statistically significant differences were observed between the two groups. In particular, there was no relationship between CD117/CD34 fractional staining score and the duration or severity of disease, despite the selection of highly symptomatic individuals requiring colonic resection. CONCLUSION: Using quantitative immunohistochemistry for CD117/CD34, we could not detect a relationship between fractional CD117/CD34 staining score and chronic constipation as compared to controls.

Adult↗
PubMed2007

Etiologic factors of chronic constipation: review of the scientific evidence.

Geriatric patient educational material and a general practice review suggest insufficient dietary fiber intake, inadequate fluid intake, decrease physical activity, side effects of drugs, hypothyroidism, sex hormones and colorectal cancer obstruction may play a role in the pathogenesis of constipation. A search of recent literature, however, reveals that there is a paucity of evidence-based publications that address the etiologic factors of chronic constipation. Much of current writings on the subject may be based primarily on myths handed down from one generation to the next. In the absence of well-designed studies, there do not appear to be sufficient evidence-based information to implicate the above as major etiologic factors in the development of chronic constipation. The etiological role of each of these factors in the development of chronic constipation deserves to be assessed by modern techniques and methodologies. Funding agencies including the government and industry sponsors should support the development of evidence-based data sets. The understanding of the etiology of chronic constipation is the foundation on which cost-effective management strategies are to be built.

Chronic Disease↗
PubMed1991

Endogenous nitric oxide modulates morphine-induced constipation.

Administration of morphine in mice causes inhibition of the gastrointestinal transit of a charcoal meal. Morphine-induced constipation in mice seems to depend predominantly on action(s) on the central nervous system since N-methyl morphine, a quaternary derivative, inhibits intestinal transit only when administered intracerebroventricularly (i.c.v.). L- but not D-arginine, given intraperitoneally, reversed the constipation induced by both morphine and its quaternary analogue. L-arginine was ineffective when given i.c.v. and did not reverse atropine-induced constipation. These results suggest that L-arginine preferentially modulates opioid-induced constipation through a stereospecific and peripheral action(s). It is possible that the effect of L-arginine is achieved by increasing the amount of nitric oxide released by non-adrenergic, non-cholinergic nerves in the gut. Thus, L-arginine may represent a useful agent for the treatment of undesirable constipation associated with the use of narcotic analgesics.

Animals↗
PubMed1989

Psychological and physiological characteristics of patients with severe idiopathic constipation.

This study prospectively evaluated psychological profiles and selected parameters of colonic and anorectal sensorimotor function in 25 consecutive patients who were referred for severe idiopathic constipation. Measurement of colonic transit of radiopaque markers divided patients into those with normal transit (n = 10) and those with slow transit (n = 15). As measured by the Hopkins Symptom Checklist, patients with normal transit constipation demonstrated significantly higher scores for psychological distress in the global symptoms index and nine clinical subscales than did those with slow transit constipation and gastrointestinal control subjects (n = 25). Both groups with constipation had decreased rectal sensation compared with controls but there was no relationship to rectal compliance or threshold of internal sphincter relaxation. There was also no relation between abnormalities of anorectal parameters, including expulsion dynamics, and psychological profiles in two groups. Measurement of colonic transit and psychological profiles in patients with severe idiopathic constipation identify two groups of patients with respect to possible pathogenesis of symptoms. Accordingly, different therapeutic approaches may be required, one behaviourally and psychologically based and the other focused on the possible modification of disordered colonic transit.

Adolescent↗
PubMed1990

The prevalence of hemorrhoids and chronic constipation. An epidemiologic study.

Hemorrhoids are a frequently occurring disorder widely believed to be caused by chronic constipation. In the present study, the epidemiology of hemorrhoids was evaluated and compared with the epidemiology of constipation. The analysis was based on 4 data sources: from the United States, the National Health Interview Survey, the National Hospital Discharge Survey, and the National Disease and Therapeutic Index; from England and Wales, the Morbidity Statistics from General Practice. Results showed that 10 million people in the United States complained of hemorrhoids, corresponding to a prevalence rate of 4.4%. In both sexes, a peak in prevalence was noted from age 45-65 yr, with a subsequent decrease after age 65 yr. The development of hemorrhoids before age 20 yr was unusual. Whites were affected more frequently than blacks, and increased prevalence rates were associated with higher socioeconomic status. This was in contrast to the epidemiology of constipation, which demonstrated an exponential increase in prevalence after age 65 yr and was more common in blacks and in families with low incomes or low social status. The data presented illustrate differences in the epidemiologic behavior of hemorrhoids and constipation, calling the presumption of causality between constipation and hemorrhoids into question.

Adult↗
PubMed1992

Dexamethasone modifies morphine-, atropine-, verapamil-induced constipation in mice.

1. The effect of dexamethasone in gastrointestinal constipation induced by morphine, verapamil and atropine in mice has been studied. 2. These drugs caused a dose-related inhibition of charcoal meal transit, which was reversed by dexamethasone. 3. Dexamethasone resulted more active in reversing morphine and atropine constipation, than in modifying verapamil effect. 4. The authors concluded that the interaction of dexamethasone on its receptor could release a larger amount of acetylcholine resulting in a reversion of atropine- or morphine-induced constipation. 5. The minor effect of dexamethasone on verapamil-induced constipation suggest a reduced involvement of calcium influx. 6. The above results suggest a role for steroid in gastrointestinal transit and propose a possible mechanism through which dexamethasone could reverse morphine- and atropine-induced constipation.

Animals↗
PubMed2006

Ileorectal anastomosis for slow transit constipation: long-term functional and quality of life results.

The results of colectomy and ileorectal anastomosis (IRA) in patients diagnosed by physiologic testing as having slow transit constipation (STC) have been reported. The durability of functional results and long-term quality of life (QoL) in these patients, however, has not been established. Between 1987 and 2002, 3670 patients were evaluated for constipation at our institution; 110 (3%) fulfilled the criteria for STC and underwent an IRA. Patients were prospectively followed and functional outcomes assessed annually by standardized questionnaires. After a median follow-up of 11 years, 104 eligible patients were mailed validated questionnaires to assess functional outcomes and QoL (Knowles-Eccersley-Scott Symptom [KESS] score, the Irritable Bowel Syndrome Quality of Life [IBS-QOL], and the SF-12 health survey). Prospectively assessed functional data was available on 85 of 104 (82%) eligible patients. At last follow-up, improvement of constipation and satisfaction with bowel function was reported by 98% and 85% of patients, respectively. Performance measures including social activity, household work, sexual life, and family relationships were reported to have improved or were not affected as a result of surgery by 75%, 86%, 81%, and 86% of the patients respectively. Fifty-nine patients (57%) responded to the study questionnaires. All 59 patients reported their constipation to be better since IRA, 83% did not require any medication, and 85% reported being satisfied with bowel function. The KESS scores of patients undergoing IRA for STC (median 6, range 0-35) were lower than reported scores of STC patients not operated upon (median 21, range 11-35, P<0.001) indicating symptomatic improvement after surgery. Mean IBS-QOL scores were similar to reported scores of patients undergoing IRA for other conditions [80 (23) versus 84 (16)], P=0.7). Mean SF-12 physical and mental summary scores were similar to reported SF-12 scores of the normal population (49.5 versus 50 and P=0.70, 48.7 versus 50, P=0.42, respectively). Ileorectal anastomosis in appropriately selected patients with slow transit constipation results in durable symptomatic relief and a long-term quality of life indistinguishable from the general population.

Adult↗
PubMed2004

Is there a role for surgery beyond colonic aganglionosis and anorectal malformations in children with intractable constipation?

PURPOSE: The aim of this study was to assess benefit of surgery in the treatment of childhood constipation in children without aganglionosis or anorectal malformations. METHODS: Retrospective chart review and follow-up questionnaire of 19 children (10 girls, age 7.6 +/- 3.9 years) who underwent surgery after colonic and anorectal manometry had documented abnormal motility. Children at the time of manometric evaluation had symptoms of intractable constipation a mean of 5.1 +/- 2.5 years. Follow-up questionnaires were administered to caregivers a mean of 11.4 +/- 9.3 months after surgical intervention. RESULTS: Proximal colonic abnormalities were seen in 2 patients, abnormalities involving the distal colon and rectosigmoid region in 13 patients, pancolonic abnormalities in 2 patients, and incomplete relaxation of the internal anal sphincter in 2 patients. Surgery led to increase in frequency of bowel movements per week (8.1 v 1.9; P <.005), decrease in soiling episodes per week (2.20 v 4.7; P <.01), and decrease in daily use of medications for constipation (0.8 v 2.3; P <.05). Adverse events included skin breakdown at site of ostomy (9%), fecal incontinence after pull-through procedure (13%), and persistent constipation (4.5%). Parents felt that the symptoms after surgery were completely resolved in 89% of patients. CONCLUSIONS: Surgery may be beneficial in the management children with chronic intractable constipation and documented abnormalities in motility.

Anastomosis, Surgical↗
PubMed1985

Severe idiopathic constipation is associated with a distinctive abnormality of the colonic myenteric plexus.

We analyzed the clinical, radiographic, esophageal manometric, and pathologic features of 26 women with severe, idiopathic constipation. Twenty-four patients were between 19 and 39 yr of age. Stool frequency was once every 5-28 days. On barium enema examination, 9 of 24 patients had colons of increased length and 4 of these 9 patients had colons of increased width (greater than 10 cm). Radionuclide solid-meal gastric-emptying studies were normal in 23 patients tested. Esophageal manometry demonstrated high-amplitude waves in 10 of 22 patients and long-duration waves in 3 of these 10 patients. Rectal biopsy specimens showed normal submucosal neurons in all patients and melanosis coli in 6. Twelve patients underwent subtotal colectomies for constipation. Conventional light microscopy using hematoxylin and eosin serial sections showed (a) melanosis coli in 4 patients; (b) normal smooth muscle in 11; (c) thinning of the circular muscle in 1; and (d) no apparent abnormalities of the myenteric plexus in any. In contrast, silver stains of the myenteric plexus showed (a) quantitatively reduced numbers of argyrophilic neurons in 10 patients; (b) morphologically abnormal argyrophilic neurons in 11; (c) decreased numbers of axons in 11; and (d) increased numbers of variably sized nuclei within ganglia in all 12. A coded analysis of the silver stains of colons from 8 patients with constipation and 19 control cases demonstrated that the pathologic abnormalities of severe idiopathic constipation could be differentiated from controls. Thus, severe idiopathic constipation is associated with a pathologically identifiable abnormality of the myenteric plexus. This abnormality appears different from anything previously described in intestinal pseudoobstruction.

Adult↗
PubMed1996

Surgical evaluation and management of refractory constipation in older children.

Chronic constipation is a common childhood problem that accounts for 3% to 5% of pediatric visits and 10% to 25% of referrals to pediatric gastroenterologists. The etiology of constipation can be elusive, and extensive investigation often fails to identify a specific cause. The authors conducted a 5-year retrospective review of the patients referred for deep transanal rectal biopsy to determine the usefulness of this procedure in the evaluation and subsequent surgical management of refractory constipation. Specimens obtained by transanal rectal biopsy established a diagnosis for 30 of the 70 patients, and 17 of these 30 had subsequent procedures in the treatment of their constipation. The authors conclude that transanal rectal biopsy identifies a significant number of patients with previously unidentified neuroenteric disorders who may benefit from additional surgery in the treatment of constipation refractory to medical management.

Biopsy↗
PubMed1995

Chronic constipation as a symptom of cow milk allergy.

Twenty-seven consecutive infants (mean age, 20.6 months) with chronic "idiopathic" constipation were studied to investigate the possible relation between constipation and cow milk protein allergy (CMPA). The infants were initially observed on an unrestricted diet, and the number of stools per day was recorded. Subsequently the infants were put on a diet free of cow milk protein (CMP) for two periods of 1 month each, separated by two challenges with CMP. During the CMP-free diet, there was a resolution of symptoms in 21 patients; during the two consecutive challenges, constipation reappeared within 48 to 72 hours. In another six patients the CMP-free diet did not lead to improvement of constipation. Only four of the patients who improved on the CMP-free diet had concomitant symptoms of suspected CMPA, but a medical history of CMPA was found in 15 of the 21 patients cured and in only one of the six patients whose condition had not improved (p < 0.05); in addition, in 15 of the 21 cured patients, results of one or more laboratory tests (specific IgE, IgG, anti-beta-lactoglobulin, circulating eosinophils) were positive at the time of diagnosis, indicating hypersensitivity, compared with one of the six patients whose condition did not improve (p < 0.05). The endoscopic and histologic findings at the time of diagnosis showed proctitis with monocytic infiltration in two patients cured with the CMP-free diet; after 1 month on this diet, they were completely normal. We conclude that constipation in infants may have an allergic pathogenesis.

Animals↗
PubMed2000

Oral naloxone reverses opioid-associated constipation.

Opioid-related constipation is one of the most frequent side effects of chronic pain treatment. Enteral administration of naloxone blocks opioid action at the intestinal receptor level but has low systemic bioavailability due to marked hepatic first-pass metabolism. The aim of this study was to examine the effects of oral naloxone on opioid-associated constipation in an intraindividually controlled manner. Twenty-two chronic pain patients with oral opioid treatment and constipation were enrolled in this study. Constipation was defined as lack of laxation and/or necessity of laxative therapy in at least 3 out of 6 days. Laxation and laxative use were monitored for the first 6 days without intervention ('control period'). Then, oral naloxone was started and titrated individually between 3x3 to 3x12 mg/day depending on laxation and withdrawal symptoms. After the 4-day titration period, patients were observed for further 6 days ('naloxone period'). The Wilcoxon signed rank test was used to compare number of days with laxation and laxative therapy in the two study periods. Of the 22 patients studied, five patients did not reach the 'naloxone period' due to death, operation, systemic opioid withdrawal symptoms, or therapy-resistant vomiting. In the 6 day 'naloxone' compared to the 'control period', the mean number of days with laxation increased from 2.1 to 3.5 (P<0.01) and the number of days with laxative medication decreased from 6 to 3.8 (P<0.01). The mean naloxone dose in the 'naloxone period' was 17.5 mg/day. The mean pain intensity did not differ between these two periods. Moderate side effects of short duration were observed in four patients following naloxone single dose administrations between 6 and 20 mg, resulting in yawning, sweating, and shivering. Most of the patients reported mild or moderate abdominal propulsions and/or abdominal cramps shortly after naloxone administration. All side effects terminated after 0.5-6 h. This controlled study demonstrates that orally administered naloxone improves symptoms of opioid associated constipation and reduces laxative use. To prevent systemic withdrawal signs, therapy should be started with low doses and patients carefully monitored during titration.

Administration, Oral↗
PubMed2004

Effect of an oral bulking agent and a rectal laxative administered alone or in combination for the treatment of constipation.

OBJECTIVES: The aim of the present study was to search for a synergetic action between psyllium and a defecation-inducing drug, Eductyl, for symptom relief in patients suffering from chronic constipation. METHODS: Twenty healthy volunteers and 20 patients complaining of chronic constipation were included in a randomized crossover study. The study was divided into four 2-weeks periods: pre-inclusion and three periods of treatment with psyllium, Eductyl, and Eductyl + psyllium respectively. Colonic transit time was determined at the end of each period of treatment. During each of the four periods, a self-administered questionnaire was used to assess symptoms of constipation. RESULTS: For constipated patients, treatment with Eductyl and Eductyl-psyllium improved clinical symptoms of constipation: increased stool frequency, resulted in fewer hard stools and less sensation of incomplete evacuation and less straining to defecate. The improvement was associated with a decrease in total and segmental colonic transit time. The Eductyl-psyllium combination did not exhibit any synergetic effect. CONCLUSION: Treatment with Eductyl alone is more efficient than with psyllium alone in providing symptom relief. Combination with psyllium is not synergetic.

Administration, Oral↗
PubMed1999

Assessment of chronic constipation: colon transit time versus defecography.

OBJECTIVE: The aim of this study was to determine the value of radiological colon transit time (CTT) measurements in relation to defecography (DFG) in chronically constipated patients. MATERIALS AND METHODS: In 30 patients with chronic constipation, total and segmental CTT was determined using radiopaque markers. In all of these patients defecography (DFG) was obtained. The patients were divided into three groups: In group I, 11 patients were classified with idiopathic constipation based on low stool frequency, normal DFG, or absence of symptoms of abnormal defecation. In group II, ten patients with rectal intussusception were diagnosed by DFG. In group III, there were nine patients with rectal prolapse or spastic pelvic floor syndrome, based on results of DFG. RESULTS: Group I, idiopathic constipation (n = 11), showed increased total CTT (mean, 93 h) and segmental CTT (right colon, 33 h (36%), left colon, 31 h (33%), rectosigmoid, 29 h (31%)). In group II, intussusception (n = 10), patients had normal mean total CTT (54 h) and a relative decrease in rectosigmoid CTT (mean, 13 h (24%)). In group III (n =9), rectal prolapse (n = 5) or spastic pelvic floor syndrome (n = 4), patients showed elevated total (mean, 167 h) and rectosigmoidal CTT (mean, 95 h (57%)). Mean total CTT was significantly different between groups I and II and between groups II and III, and mean rectosigmoidal CTT was significantly different between all three groups (P < 0.05). CONCLUSION: The use of total and rectosigmoidal CTT helps to identify the underlying pathophysiology of chronic constipation. Furthermore CTT helps to identify patients, who may benefit from DFG.

Adult↗
PubMed1995

Constipation and diarrhea: the neglected symptoms.

OBJECTIVE: To review the symptom experience of constipation and diarrhea related to cancer and its treatment. DATA SOURCES: Published articles and book chapters relating to constipation and diarrhea in patients with cancer. CONCLUSIONS: Constipation and diarrhea often represent a major concern and source of discomfort for the cancer patients. Research is needed to establish prevention and treatment protocols for patients at risk for constipation or diarrhea. IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses are in an excellent position to recognize individuals who are at high risk for constipation and diarrhea. Preventive strategies and treatment protocols are of utmost importance.

Cathartics↗
PubMed2002

Low-dose oral naloxone reverses opioid-induced constipation and analgesia.

The most common side effect of opioid therapy is constipation. It is often difficult to treat and is believed to be primarily a peripheral effect. Single large doses of oral naloxone have been shown to be efficacious in reversing opioid-induced constipation. However, they often cause the unwanted side effect of analgesia reversal. This study evaluated the effects on constipation and analgesia of low doses of oral naloxone given three times daily. Patients taking stable doses of opioids with complaints of constipation were recruited for this double-blind, randomized, placebo-controlled study. Patients were given 4 mg or 2 mg of oral naloxone, or placebo, three times daily. Stool frequency and symptoms related to constipation were recorded daily. Patients also recorded the daily amount of analgesics required to maintain pain control. Nine patients were recruited for the study. All the patients who received oral naloxone had some improvement in their bowel frequency. Three of the patients also experienced reversal of analgesia, including one who had complete reversal of analgesia. This study demonstrates that reversal of analgesia still occurred despite dividing the oral naloxone into very low doses relative to the total dose of opioid used. Patients using high doses of opioids appear to be the most vulnerable to the analgesic effect of oral naloxone.

Administration, Oral↗
PubMed2000

How useful is docusate in patients at risk for constipation? A systematic review of the evidence in the chronically ill.

The effectiveness of docusate for constipation has not been studied in the terminally ill. Controversy also exists concerning its effectiveness in the chronically ill. Because chronically ill patients and terminally ill patients have several risk factors for constipation in common, we undertook a systematic review of prospective controlled trials of oral docusate in the chronically ill to clarify the utility of this drug in populations with advanced disease. The data sources were Medline 1966-April 1997, CINAHL 1982-April 1997, Current Contents August 1996-April 1997, Cochrane Library, a hand search of Index Medicus 1940-1966, three palliative care journals, references in relevant articles and texts, and direct contact with experts. Prospective controlled trials evaluating oral docusate in humans with chronic illness and identifiable risk factors for, or preexisting, constipation were selected. Only materials abstracted in English or French were considered. Information was collected by two independent reviewers and included patient demographic data, study design, dose of docusate, outcomes of stool consistency, stool frequency, need for other laxatives, and assessment of methodologic and reporting quality. Of nine identified studies, four were eligible. These incorporated three different designs and sample sizes that ranged from 15 to 74. Quality assessment scores were low (range 0.46-0.52 with a perfect score being 1.0). Three studies were flawed in blinding of treatment allocation and the use of co-interventions. All studies showed a small trend toward increased stool frequency on docusate. Because of significant clinical heterogeneity in the identified studies, pooled data analysis was not feasible. At present, the use of docusate for constipation in palliative care is based on inadequate experimental evidence. Randomized controlled trials with chronically ill patients and patients with advanced disease are needed to determine its role in prevention and treatment of constipation.

Adolescent↗