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PubMed1993

Similar functional results after restorative proctocolectomy in patients with familial adenomatous polyposis and mucosal ulcerative colitis.

Restorative proctocolectomy (RP) is generally considered to achieve better results in patients with familial adenomatous polyposis (FAP) than in those with mucosal ulcerative colitis (MUC). We studied 39 pairs of patients (FAP versus MUC), individually matched for surgeon (n = 4), types of ileal pouch (19 S-pouches and 20 J-pouches), technique of ileal pouch-anal anastomosis (21 stapled, 18 handsewn with mucosectomy), duration of follow-up after pouch function (median: 32 months; range: 6 months to 8.5 years), age (median: 30 years; range: 12 to 60 years), and gender (male-to-female ratio: 1.4:1.0). The median duration of operation (3.2 hours), hospital stay (9 days), and the amount of blood loss (about 650 mL) were similar between the two groups. The patients in the MUC group tended to have a higher overall complication rate (28% versus 21%) and more pouch-related septic complications (13% versus 8%, p = 0.6 by chi 2 analysis). Functional results were similar for daytime (median: 5 per day) and nighttime (median: 1 per night) stool frequency and the median duration that defecation could be deferred (median: about 1.5 hours). Perfect continence was present in 34 (87%) patients during the day and in 19 (49%) patients during the night in each group. The use of antidiarrheal medications did not differ between the two groups. According to an analogue scale (from 1 to 10, with 10 being best), the quality of life and health and satisfaction with outcome (median score: 9) were identical between the groups. Thus, in closely matched groups of patients with FAP and MUC, the functional outcome after RP was similar. However, pouchitis was more common in the MUC group (33% versus 10%, p < 0.05 by chi 2 analysis).

Adenomatous Polyposis Coli↗
PubMed1998

Effects of aging on the functional outcome of coloanal anastomosis with colonic J-pouch.

BACKGROUND: Many low rectal cancers can be treated radically by proctectomy with total mesorectal excision followed by colonic J-pouch anal anastomosis (CPAA). In elderly patients, the fear of poor function might reduce indications for CPAA in favor of abdomino-perineal excision with end stoma. METHODS: Among 198 patients with CPAA operated on for low rectal cancer between 1984 and 1992, 20 patients over 75 years old were alive without recurrence at the time of telephone interview (July 1995). Minimal follow-up was 3 years (mean 8) for all patients. Their functional results were compared with those of 37 younger patients operated consecutively during the last 5 years of the study period. RESULTS: The two groups were well matched for gender, tumor distance from the anal verge, histologic staging, and use of adjuvant radiotherapy. Follow-up was longer in the elderly group than in the young group (96 versus 63 months, respectively). The elderly group had a median of 1 bowel movement per day and the young group a median of 1.5 (P = 0.13). The presence of irregular intestinal transit was reported in 48% of the aged and in 35% of the young group (P = 0.6), but fragmented defecation was less frequent (25% versus 47%, respectively; P = 0.15). Urgency was noted, respectively, in 15% and 22% of elderly and young patients (P = 0.7) and constipation in 40% and 22% (P = 0.2). Incontinence for feces (15%) and for flatus (40%) in elderly were not significantly different from the younger group (14% and 46%, P = 1.0 and P = 0.8, respectively). Laxatives were used in 32% of elderly and 17% of young patients (P = 0.3). CONCLUSION: Functional outcome may be good to excellent in elderly patients after CPAA and compares well with that obtained in younger patients. Constipation, however, may be more frequent in the elderly. Age is not a contraindication for CPAA if the sphincter tone is clinically normal.

Adenocarcinoma↗
PubMed1995

Level of the anastomosis does not influence functional outcome after anterior rectal resection for rectal cancer.

Anorectal function was studied in 55 patients undergoing low anterior resection for rectal adenocarcinoma. Patients were examined preoperatively and 3 months postoperatively by anorectal manometry and standardized interview. Postoperatively, the patients showed, in general, an impairment of anorectal functions. After 3 months, continence for flatus was defective, the ability to discriminate flatus from feces, and the ability to defer defecation were compromised. Stool frequency was elevated, and anal resting pressure, squeeze pressure, and rectal compliance were decreased. The rectoanal inhibitory reflex was abolished in all patients. However, the two groups with the level of the anastomosis less than or equal to 6 cm (n = 27, range 3 to 6) and more than 6 cm (n = 28, range 7 to 10) above the anal verge showed no differences in manometric values, stool frequency, or fecal continence assessed by the interview. No correlation was found between the level of the anastomosis and manometric values and between the level of the anastomosis and stool frequency (regression analysis = not significant). We concluded that anorectal function after anterior resection and low colorectal anastomosis are not influenced by the remaining length of the rectum but by the surgical trauma to the sphincter and its innervation.

Adenocarcinoma↗
PubMed2001

Role of CRF receptor 1 in central CRF-induced stimulation of colonic propulsion in rats.

The CRF receptor subtype mediating the colonic and gastric motor responses to central CRF was investigated in conscious rats. CRF (0.6 microg/rat) injected intracerebroventicularly (i.c.v.) or 1 h water avoidance stress stimulated defecation (pellet/60 min: 4.1+/-1.0 and 8.7+/-0.7 respectively vs. 0.3+/-0.3 in i.c.v. vehicle/no stress). The CRF receptor 1 (CRF-R1) antagonist, NBI-27914 (50-100 microg/rat) injected i.c.v., abolished the colonic response to i.c.v. CRF and dose-dependently reduced that induced by water avoidance stress. NBI-27914 (100 microg/rat) injected peripherally did not influence the defecatory response to stress. The peptide CRF-R1/R2 antagonist, astressin (10 microg/rat, i.c.v.) inhibited the colonic motor response to i.c.v. CRF and stress similarly as NBI-27914 injected i.c.v. at 100 microg/rat. Intracisternal (i.c.) injection of astressin (10 microg/rat) also completely prevented CRF (0.6 g, i.c.)-induced delayed gastric emptying while i.c. NBI-27914 (50 or 100 microg) had no effect. These results indicate a differential role of central CRF receptor subtypes in the colonic stimulatory and gastric inhibitory motor responses to central CRF and that the CRF component of stress-related activation of colonic expulsion is primarily mediated by CRF-R1.

Animals↗
PubMed2003

A novel water-soluble selective CRF1 receptor antagonist, NBI 35965, blunts stress-induced visceral hyperalgesia and colonic motor function in rats.

The stress response involves the activation of two corticotropin-releasing factor (CRF) receptor subtypes. We investigated the role of CRF1 in stress-related visceral responses. A novel water-soluble tricyclic CRF1 antagonist, NBI 35965 was developed that displayed a high affinity for CRF1 (Ki approximately 4 nM) while having no binding affinity to CRF2. This antagonist also inhibited the stimulation of cAMP induced by sauvagine in CRF1 transfected cells. NBI 35965 administered per orally (p.o.) in rats (1, 3, 10 or 30 mg/kg) inhibited dose-dependently [125I]sauvagine binding selectively at brain sites of CRF1 distribution as shown by ex vivo receptor autoradiography. At the highest doses, NBI 35965 completely prevented [125I]sauvagine labeling in the cortex. NBI 35965 (10 mg/kg) administered p.o. or subcutaneously (s.c.) 1 h before intravenous CRF completely blocked the 81% shortening of distal colonic transit time induced by CRF. NBI 35965 (20 mg/kg s.c.) significantly reduced the defecation in response to water avoidance stress but not that induced by s.c. carbachol. In adult male Long-Evans rats that had undergone maternal separation, acute water avoidance stress significantly increased the visceromotor response to colorectal distention (20-80 mmHg) by 42+/-19% compared with the response before stress. Stress-induced visceral hyperalgesia was abolished by NBI 35965 (20 mg/kg, s.c.). The data show that NBI 35965 is a novel water-soluble selective CRF1 antagonist with bioavailability to the brain upon peripheral administration and that CRF1 receptor signaling pathways are involved in water avoidance stress-induced hyperalgesia to colorectal distention and stimulation of colonic transit.

Amphibian Proteins↗
PubMed1998

Regulation of contextual conditioning by the median raphe nucleus.

The median raphe nucleus (MRN) has been suggested as the origin of a behavioral inhibition system that projects to the septum and hippocampus. Electrical stimulation of this mesencephalic area causes behavioral and autonomic manifestations characteristic of fear such as, freezing, defecation and micturition. In this study we extend these observations by analyzing the behavioral and autonomic responses of rats with lesions in the MRN submitted to a contextual conditioning paradigm. The animals underwent electrolytic or sham lesions of the median raphe nucleus. One day (acute) or 7 days (chronic) later they were tested in an experimental chamber where they received 10 foot-shocks (0.7 mA, 1 s with 20-s interval). The next day, sham and MRN-lesioned animals were tested again either in the same or in a different experimental chamber. During this, the duration of freezing, rearings, bouts of micturition and number of fecal boli were recorded. Sham-operated rats placed in the same chamber showed more freezing than rats exposed to a different context. This freezing behavior was clearly suppressed in rats with acute or chronic lesions in the MRN. MRN lesions also reduced the bouts of micturition and number of fecal boli. These rats showed a reduced number of rearings than sham-lesioned rats. This effect is probably the result of the displacement effect provoked by freezing since no significant differences in the number of rearings could be observed between these animals and the NMR-lesioned rats tested in an open field. This lesion produced higher horizontal locomotor activity in this test than the controls (sham-lesioned rats). These results point to the importance of the median raphe nucleus in the processing of fear conditioning with freezing being the most salient feature of it. Behavioral inhibition is also under control of MRN but its neural substrate seems to be dissociated from that of contextual fear.

Animals↗
PubMed2000

Long-term fluoxetine produces behavioral anxiolytic effects without inhibiting neuroendocrine responses to conditioned stress in rats.

The aim of the present study was to investigate the anxiolytic effects of long-term treatment with fluoxetine in rats. Selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, are used to treat anxiety and panic disorders, in addition to treating depression. A major concern with SSRIs is a 2-3-week delay in their therapeutic effects. SSRIs share with anxiolytic 5-HT(1A) agonists the ability to produce desensitization of post-synaptic 5-HT(1A) receptors. To investigate the anxiolytic effects of fluoxetine, rats were treated for 14 days with fluoxetine (10 mg kg(-1) day(-1), i.p. ). The rats were stressed using a conditioned stress procedure and tested one day after the last fluoxetine injection. Fluoxetine decreased stress-induced defecation (by 60%), reversed the stress-induced suppression of exploring behavior (by 59%) and shortened the duration of stress-induced freezing behavior (by 11. 5%). However, the stress-induced increase in plasma levels of ACTH, corticosterone, oxytocin, prolactin and renin were not inhibited by fluoxetine treatment. These findings suggest that neuroadaptive changes induced by sustained inhibition of serotonin (5-HT) reuptake, contribute to the mechanism of the anxiolytic effects of fluoxetine. In contrast, the neuroendocrine responses to conditioned stress are not affected by these neuroadaptive changes.

Adrenocorticotropic Hormone↗
PubMed2001

A novel 5-HT3 receptor agonist, YM-31636, increases gastrointestinal motility without increasing abdominal pain.

We examined the effects of YM-31636 (2-(1H-imidazol-4-ylmethyl)-8H-indeno[1,2-d]thiazole monofumarate), a novel 5-HT3 receptor agonist, on gastrointestinal functions including visceral pain reflex in rats. Injection of YM-31636 increased the number of fecal pellets. This effect was completely inhibited by ramosetron, a 5-HT3 receptor antagonist. YM-31636 also increased the intracolonic pressure measured in both conscious and anesthetized rats. In isolated distal colon, YM-31636 increased the short-circuit current response. This effect was abolished by ramosetron. Both the maximal response and the potency of YM-31636 were weaker than those of other 5-HT3 receptor agonists. In two visceral pain reflex models, YM-31636 neither changed the magnitude of pressor response to colonic distension in anesthetized rats nor affected the visceromotor threshold to colorectal distension in conscious rats. In conclusion, YM-31636 facilitated defecation without increasing visceral pain. Consequently, 5-HT3 receptor agonists like YM-31636 would be promising in the treatment of chronic constipation.

Abdominal Pain↗
PubMed1997

Gastrointestinal motor activity in conscious ferrets.

Gastrointestinal motility was measured with force transducers in conscious ferrets. The gastrointestinal motility pattern in both the interdigestive and digestive states was similar to that reported for humans. The activity front, phase III contractions of the migrating motor complex, occurred cyclically in the antrum and migrated to the duodenum and ileum in the interdigestive state, and relatively low-amplitude contractions were sustained in the antrum, duodenum and ileum in the digestive state. Colonic motility was characterized by basal relatively low-amplitude contractions and a single high-amplitude contraction preceding defecation. Cisapride (0.3-3 mg/kg s.c.) enhanced antral and colonic motility. This ferret model will help the investigation and evaluation of drug effects on gastrointestinal motility in humans.

Animals↗
PubMed1997

Effects of ondansetron administration on opioid withdrawal syndrome observed in rats.

This study tested whether a 5-HT3 receptor antagonist could reverse the signs of precipitated opioid withdrawal. Rats were treated with either saline or morphine for 4 days. After the four days, half of the rats in each group received naloxone and half received saline. Each animal also received one of four doses of ondansetron (0, 1, 2 and 4 mg/kg i.p.). Administration of ondansetron to rats receiving naloxone after chronic morphine decreased the intensity of withdrawal signs such as increased defecation, jumping and wet-dog shakes, elevated the nociceptive threshold values which were decreased by precipitated withdrawal, but produced no change in urination, rectal temperature or salivation. The effects exhibited by ondansetron administration may be explained through interference of its 5-HT3 receptor antagonist activity with serotoninergic mechanisms involved in the regulation of these withdrawal symptoms. The use of this drug is thus suggested as a possible treatment of opioid withdrawal signs in heroin addicts.

Animals↗
PubMed1997

The discovery and a study of the adventitia rectalis, a fibrous layer of the rectal wall.

In sacral anoplasty, it is frequently found that an outer layer of the rectal wall, which resembles the structure of the taenia bands of the colon, limits the elasticity of the rectum making it different from the small intestine, hence preventing the rectal stump from being advanced to reach the perineum. Results of autopsy studies on 40 human babies and 40 dogs showed that a special collagenous fibrous layer called adventitia rectalis was found to limit the free expansion of the rectal wall. This was responsible for keeping the rectum a straight tubular shape with a fixed volume. This tissue plays an important role in bowel movement by defining a threshold of intrarectal pressure in the bowel reflex of defecation and by transmitting the expulsive force from the abdomen above down to the anal opening. This discovery may explain why (1) in Hirschsprung's disease, the preservation of the rectal wall in Soave's or Rehbein's procedure or partial preservation in Duhamel's operation will preserve better bowel function; (2) in atresia ani, rectal tapering results in better bowel control than rectal pouch amputation; and (3) in sacral anoplasty, multiple releasing incisions of adventitia rectalis at different levels will lengthen the rectal stump to about double its original length to reach the perineal incision, and the divided fibers will soon regenerate.

Anal Canal↗
PubMed1997

Do children with repaired low anorectal malformations have normal bowel function?

PURPOSE: The authors' aim was to compare bowel function in patients who had undergone repair of a low anorectal malformation with that of normal healthy children. METHODS: The bowel function of 40 patients (29 boys, 11 girls; median age, 7; range, 3 to 13) with low anorectal malformations was evaluated by a multivariate scoring method based on a questionnaire. All patients were toilet trained for defecation and micturition. They were also evaluated clinically, and the outcome was graded as excellent (normal bowel function), good (no or minor social limitations), fair (marked social limitations), or poor (total incontinence). Fifty-four healthy children with a similar age and gender distribution were used as controls. RESULTS: Twenty-one patients (52%) with normal bowel function had continence scores within the range of the scores of healthy children (patients, 19.3 +/- 0.7 v controls, 19.1 +/- 1.3). Fifteen patients had a good clinical outcome. The mean score in this group was 16.3 +/- 2.4. Four patients with a fair outcome had a mean score of 10.5 +/- 2.9. Constipation requiring dietary or medical treatment was reported by 17 patients (42%) and four of the controls (7%). Daily soiling caused by fecal overflow was reported by four patients (10%) and none of the controls. None of the patients had urinary incontinence; occasional wetting was found in 27% of the patients and 22% of the controls (P = .56). CONCLUSION: Only half of the children with a low anorectal malformation have age-appropriate normal bowel function. Long-term follow-up of these patients to manage the main functional problem, constipation, is warranted.

Anus, Imperforate↗
PubMed2000

Effect of the dietary fiber glucomannan on chronic constipation in neurologically impaired children.

OBJECTIVE: Inadequate dietary fiber intake is a widely accepted explanation for chronic constipation in children with severe brain damage. The aim of our study was to evaluate the efficacy of glucomannan, a soluble fiber, as a treatment for chronic constipation in these children. STUDY DESIGN: Twenty children with severe brain damage and chronic constipation were randomly assigned to double-blind treatment with either glucomannan (n = 10) or placebo (n = 10) for 12 weeks. Stool habits, total and segmental gastrointestinal transit times, and anorectal motility were evaluated in all children before and after the treatment period. RESULTS: Glucomannan significantly increased (P <.01) stool frequency, whereas the effect of placebo was not significant. Laxative or suppository use was significantly reduced (P <.01) by glucomannan but was not affected by placebo. Clinical scores of stool consistency were significantly improved and episodes of painful defecation per week were significantly reduced by glucomannan (P <.01) but not by placebo. However, neither glucomannan nor placebo had a measurable effect on total and segmental transit times. CONCLUSIONS: In neurologically impaired children, glucomannan improves stool frequency but has no effect on colonic motility.

Administration, Rectal↗
PubMed1977

Electrical stimulation of the rectal ampulla causing reflex voiding.

Electrical stimulation of the rectal ampulla resulted in a desire to void and defecate in 11 patients with an intact nervous system. There was a contraction of the detrusor and the rectal ampulla with relaxation of the anal sphincter. Electrical stimulation of the rectal ampulla and anal sphincter has clinical applications in patients with incontinence of, or inability to empty, the lower urinary tract or fecal system.

Anal Canal↗
PubMed1988

Encopresis and constipation in children.

Chronic retentive constipation in children is common, often undertreated, and frequently resistant to standard treatment. A new understanding of abnormal defecation dynamics has evolved to complement the established medical behavior model of this condition. The primary care pediatrician is in an excellent position to facilitate prevention through counseling on normal bowel habits and early intervention. A comprehensive medical behavior intervention program can be supervised effectively by the pediatrician providing benefit to most patients. Those who are compliant with treatment and are resistant to intervention may benefit by extensive evaluation of anorectal dynamics and use of such teaching as biofeedback training.

Child↗
PubMed1997

Differential effects of intrathecal thyrotropin-releasing hormone (TRH) on perineal reflexes in male rats.

The effects of thyrotropin-releasing hormone (TRH) on the sexual and defecatory reflexes regulated by pudendal motoneurons were investigated. Intrathecal TRH (10 microliters volume; 0.0, 0.01, 1.0 or 100 microM concentration) at lumbosacral spinal segments (L4-S1) in acute preparations produced a dose-dependent increase in external anal sphincter (EAS), but not bulbospongiosus (BS), electromyographic (EMG) activity. Intraspinal (L6) injection of 100 microM TRH (1 microliter/micropipette), significantly increased EAS EMG activity in acute preparations. Electromyographic activity of the BS muscle was unchanged. All doses of intrathecal TRH (10 microliters volume; 0, 10, 50, 100, or 500 microM concentration) in awake animals significantly reduced the proportion of responders to a penile reflex test. Subsequently, all measures of penile reflexes were significantly reduced. Glans tumescence and defecation bouts before or during penile reflex testing were unaffected by intrathecal TRH as were indices of behavioral and motor hyper-reactivity analogous to that produced by serotonin. These data indicate that pudendal motoneurons, in the dorsomedial nucleus, are differentially regulated by neuropeptides present in the lumbosacral spinal cord.

Anal Canal↗
PubMed1999

Opposite effects of gentle handling on body temperature and body weight in rats.

Opposite effects of gentle handling on body temperature and body weight in rats. PHhe aim of this study was to measure the body weight set point when rats are being handled gently and thus experience emotional rise in body temperature. Wistar male rats were used in this experiment, and each rat was its own control. Body weight set point was estimated from the rat's food hoarding behavior. The set point is the intersection of the regression line for hoarding with the X axis. During hoarding sessions the experimenter handled the rat and took its colonic temperature six to eight times, an action sufficient to arouse emotional fever. On alternate days the rats were not handled. Thus, body weight set point was obtained for each rat without handling and with handling. In sessions with handling, rats raised their body temperature, ate less, and defecated more than in control sessions. When handled, the body weight set point declined from 388 +/- 44 g to 366 +/- 47 g (p = 0.048, t = 2,39). The decline in the set point induced by gentle handling is believed to result from an elevation of the hypothalamic CRH.

Animals↗
PubMed1988

Pelvic floor physiology.

Pelvic floor physiology is poorly understood. The funnel shape of the pelvic floor and anal canal is uniquely developed to provide discriminatory continence of gas, liquid, and solid. Proximally, the pelvic floor consists of the pubococcygeus and iliococcygeus muscles. Distally, the anal canal is surrounded by the internal and external sphincter muscles. The anorectal ring is situated between the proximal pelvic floor and the distal anal canal. It is the site of the puborectalis muscle, which is anatomically, neurologically, and functionally merged with the deep portion of the external sphincter muscle. It is at this site that unique forces act to create both a flutter valve and the anorectal angle with the flap valve. Extrinsic pressures at this level reinforce both the flap valve and the flutter valve. Intrinsic pressures are generated by all of the surrounding muscles to produce a high-pressure zone. These factors are critical, but many other factors, such as rectal capacity, compliance, colonic transit, motility, and sensory mechanisms, also interact in a complex way to provide normal continence and defecation. Not surprisingly, no single test allows a complete assessment of the interactions of all these factors. Nevertheless, analysis of components thought to be important in pelvic floor physiology has contributed significantly to the understanding of normal as well as abnormal physiology. Although clinical evaluation continues to be the cornerstone of the diagnosis of pelvic floor disorders, anorectal physiological testing has contributed significantly to our understanding of the dynamics of the pelvic floor. With the refinement of existing techniques and the addition of new investigative tools, it is anticipated that knowledge of pelvic floor physiology will continue to grow.

Anal Canal↗