Functional Anatomy Coloproctology
Brain or gut? Site of action of adrenomedullin to regulate gut motility.
J Gastroenterol. 2005 Dec;40(12):1161-2.
Anastomosis of Riolan revisited: the meandering mesenteric artery.
van Gulik TM, Schoots I
Arch Surg. 2005 Dec;140(12):1225-9.
The eponym anastomosis of Riolan suggests that Jean Riolan (1580-1657), a famous 17th century French anatomist, was the first to describe this mesenteric arterial connection between the superior and inferior mesenteric arteries. Riolan was a strong defender of traditional Galenic doctrine in medicine and proved a vigorous opponent of the new concept of the circulation of blood as exposed by William Harvey (1578-1657). As confirmed by examining his anatomy book published in 1649, it is unlikely that Riolan would have conceived an arterial collateral pathway in the mesocolon. He probably had observed vascular arcades running along the inner border of the colon. It was not until 1743 that Albrecht von Haller (1708-1777) gave a detailed description of the anatomy of the mesenteric arteries, referring to the arterial collateral connection between the superior and inferior mesenteric arteries as the Arcus Riolani in honor of an old master of anatomy.
Effect of atilmotin on gastrointestinal transit in healthy subjects: a randomized, placebo-controlled study.
Park MI, Ferber I, Camilleri M, Allenby K, Trillo R, Burton D, Zinsmeister AR
Neurogastroenterol Motil. 2006 Jan;18(1):28-36.
We studied effects of i.v. atilmotin (BAX-ACC-1638, a novel motilin agonist, circulating t(1/2) <10 min) on gastrointestinal transit in humans using a randomized, parallel-group, dose-response double-blind study of i.v. atilmotin, 6, 30, 60 mug or vehicle (placebo) given 2 min after standardized breakfast, lunch and dinner. The breakfast meal contained (99m)Tc-eggs and (111)In-milk. Full gastrointestinal transit was measured by scintigraphy. Primary endpoints were % gastric emptying (GE) at 30 min, GE t(1/2), colonic filling (CF) at 6 h, and geometric centre of colonic transit at 24 h. Analysis included adjustment for age, gender and body mass index, with Bonferroni correction applied for multiple comparisons. A significant treatment effect of atilmotin was detected for GE (%) at 30 min for solids and liquids (P < 0.01 for both). There were no significant effects on CF or CT and no significant adverse clinical events. Thus, atilmotin accelerates GE of solids and liquids in healthy humans. These data suggest that, at the doses tested, atilmotin should be considered for treatment of stomach motility disorders.
Developmental study of tethered spinal cord in murine embryos with anorectal malformations.
Tsuda T, Shimotake T, Aoi S, Kume Y, Deguchi E, Iwai N
J Pediatr Surg. 2005 Dec;40(12):1927-30.
BACKGROUND/PURPOSE: Tethered spinal cord is frequently associated with anorectal malformations (ARMs). However, it remains unknown how the tethered spinal cord develops and relates to the severity of ARM. We studied the development of the spinal cord in ARM mouse embryos induced by all-trans retinoic acid (ATRA). METHODS: Pregnant ICR-Slc mice were administered 100 mg/kg of ATRA on the ninth embryonic day (E9.0). Embryonic specimens were obtained from the uteri between E11.0 and E18.5. Midsagittal histologic sections focusing on the spinal cord and pelvis were prepared for immuonhistochemistry specific for neurofilament and Protein Gene Product 9.5 molecules. RESULTS: More than 98% of ATRA-treated embryos demonstrated ARM with rectourethral or rectocloacal fistula. Normal embryos exhibited progressive ascent of the spinal cord from E14.5. However, in ARM embryos, the distal spinal cord ended with meningomyelocelelike or atypical hamartomatous lesions at E11.5 to E13.5, which later caused stretch force that damaged the spinal cord, resulting in tethered cord between E16.0 and E16.5. CONCLUSIONS: In ATRA-induced ARM mouse embryos, tethered spinal cord was mostly established, accompanied by caudal neural maldevelopment, during early fetal development. This experimental model may be useful for researching detailed neuropathologic conditions in ARM children accompanied with tethered spinal cord.
Barostat testing of rectal sensation and compliance in humans: comparison of results across two centres and overall reproducibility.
Cremonini F, Houghton LA, Camilleri M, Ferber I, Fell C, Cox V, Castillo EJ, Alpers DH, Dewit OE, Gray E, Lea R, Zinsmeister AR, Whorwell PJ
Neurogastroenterol Motil. 2005 Dec;17(6):810-20.
We assessed reproducibility of measurements of rectal compliance and sensation in health in studies conducted at two centres. We estimated samples size necessary to show clinically meaningful changes in future studies. We performed rectal barostat tests three times (day 1, day 1 after 4 h and 14-17 days later) in 34 healthy participants. We measured compliance and pressure thresholds for first sensation, urgency, discomfort and pain using ascending method of limits and symptom ratings for gas, urgency, discomfort and pain during four phasic distensions (12, 24, 36 and 48 mmHg) in random order. Results obtained at the two centres differed minimally. Reproducibility of sensory end points varies with type of sensation, pressure level and method of distension. Pressure threshold for pain and sensory ratings for non-painful sensations at 36 and 48 mmHg distension were most reproducible in the two centres. Sample size calculations suggested that crossover design is preferable in therapeutic trials: for each dose of medication tested, a sample of 21 should be sufficient to demonstrate 30% changes in all sensory thresholds and almost all sensory ratings. We conclude that reproducibility varies with sensation type, pressure level and distension method, but in a two-centre study, differences in observed results of sensation are minimal and pressure threshold for pain and sensory ratings at 36-48 mmHg of distension are reproducible.
Functional gastrointestinal disorders and mast cells: implications for therapy.
Barbara G, Stanghellini V, de Giorgio R, Corinaldesi R
Neurogastroenterol Motil. 2006 Jan;18(1):6-17.
The pathophysiology of functional gastrointestinal disorders is poorly understood. Accepted common mechanisms include psychosocial factors, abnormal gastrointestinal motility and disturbed visceral sensory perception, but the underlying causes remain unclear. Mast cells (MCs) are immunocytes widely distributed throughout the gastrointestinal tract. Several stimuli (e.g. allergens, neuropeptides and stress) lead to MC activation with consequent mediator release (e.g. histamine, tryptase and prostanoids). The MC mediators interact with nerves supplying the gut leading to altered gut physiology and increased sensory perception. The intestinal mucosa of irritable bowel syndrome patients contains on average an increased number of MCs. These cells release an increased amount of mediators in close vicinity to mucosal innervation. The MC activation and their close proximity to nerve fibres is correlated with the severity of perceived abdominal painful sensations. These data provide a strong basis for considering MCs as important participants in visceral hypersensitivity and pain perception in irritable bowel syndrome. Inhibition of MC function may ameliorate irritable bowel symptoms. Novel drugs with an increased potential in the control of MC function (e.g., anti-IgE antibodies, the intracellular protein tyrosine kinase inhibitor Syk) and mediator release (e.g., second generation antihistamines, proteinase-activated receptor antagonists) may be useful pharmacological tools for these common disorders.
Brain activation responses to subliminal or supraliminal rectal stimuli and to auditory stimuli in irritable bowel syndrome.
Andresen V, Bach DR, Poellinger A, Tsrouya C, Stroh A, Foerschler A, Georgiewa P, Zimmer C, Monnikes H
Neurogastroenterol Motil. 2005 Dec;17(6):827-37.
Visceral hypersensitivity in irritable bowel syndrome (IBS) has been associated with altered cerebral activations in response to visceral stimuli. It is unclear whether these processing alterations are specific for visceral sensation. In this study we aimed to determine by functional magnetic resonance imaging (fMRI) whether cerebral processing of supraliminal and subliminal rectal stimuli and of auditory stimuli is altered in IBS. In eight IBS patients and eight healthy controls, fMRI activations were recorded during auditory and rectal stimulation. Intensities of rectal balloon distension were adapted to the individual threshold of first perception (IPT): subliminal (IPT -10 mmHg), liminal (IPT), or supraliminal (IPT +10 mmHg). IBS patients relative to controls responded with lower activations of the prefrontal cortex (PFC) and anterior cingulate cortex (ACC) to both subliminal and supraliminal stimulation and with higher activation of the hippocampus (HC) to supraliminal stimulation. In IBS patients, not in controls, ACC and HC were also activated by auditory stimulation. In IBS patients, decreased ACC and PFC activation with subliminal and supraliminal rectal stimuli and increased HC activation with supraliminal stimuli suggest disturbances of the associative and emotional processing of visceral sensation. Hyperreactivity to auditory stimuli suggests that altered sensory processing in IBS may not be restricted to visceral sensation.
Desensitization of the peristaltic reflex induced by mucosal stimulation with the selective 5-HT4 agonist, tegaserod.
Am J Physiol Gastrointest Liver Physiol 2005 Oct 13;.
The intestinal peristaltic reflex induced by mucosal stimulation is mediated by mucosal release of 5-HT, which acts on 5-HT4 receptors located on CGRP-containing afferent nerve terminals. Exposure of the colonic mucosa to the 5-HT4 receptor agonist, tegaserod, in the range of 1 nM to 10 microM elicits a peristaltic reflex and stimulates colonic propulsion. The present study was designed to identify the 5-HT4 receptor subtype mediating the reflex and determine whether functionally effective concentrations of tegaserod desensitize the reflex induced by mucosal stimulation. Exposure of rat colonic mucosa to tegaserod in the range of 5 nM to 5 microM for 5 or 10 min caused rapid time- and concentration-dependent desensitization of the peristaltic reflex induced by mucosal stroking, consistent with the operation of a rapidly-desensitizing 5-HT4b receptor subtype. Desensitization was accompanied by decrease in CGRP release. The rate of recovery of peristaltic response depended on the desensitizing concentration of tegaserod: ascending contraction and descending relaxation recovered within 15 min after 5 to 50 nM tegaserod, 30 min after 0.5 microM, and 60 min after 5 microM. Neither CGRP release nor the peristaltic reflex induced by muscle stretch was affected by 5-HT4 receptor desensitization, providing further evidence that 5-HT does not mediate the reflex induced by muscle stretch. These results suggest in cases of increased 5-HT availability or prolonged exposure, such as colitis, it is likely that the peristaltic reflex will be blunted.
The Herbal Medicine, Dai-Kenchu-To, Accelerates Delayed Gastrointestinal Transit after the Operation in Rats.
Fukuda H, Chen C, Mantyh C, Ludwig K, Pappas TN, Takahashi T
J Surg Res 2005 Oct 28;.
BACKGROUND: Post-operative ileus (POI) is a transient bowel dysmotility after operation. We have previously shown that laparotomy alone significantly delayed gastrointestinal (GI) transit, compared to anesthesia alone. The GI transit was further delayed after laparotomy plus intestinal manipulation. Dai-Kenchu-to (DKT), an herbal medicine, has been used for treating adhesive bowel obstruction in Japan. We studied whether DKT improves delayed GI transit after the operation, with or without morphine administration in rats. MATERIALS AND METHODS: Under isoflurane anesthesia, POI was induced by laparotomy with intestinal manipulation. Immediately after the operation, the rats received (51)Cr by gavage. Three hours after the operation, the rats were sacrificed and GI transit was estimated by calculating the geometric center (GC). DKT (120, 360, and 1,200 mg/kg) were administered by gavage after the operation, with or without morphine administration (1 mg/kg s.c.). A muscarinic receptor antagonist (atropine; 50 mug/kg), a 5HT(3) receptor antagonist (ondansetron; 1 mg/kg) and a 5HT(4) receptor antagonist (GR113,808; 3 mg/kg) were administered before the operation. Truncal vagotomy was performed preceding the operation. RESULTS: Laparotomy with intestinal manipulation produced a significant delay in GI transit (GC = 2.93 +/- 0.16), compared to that of anesthesia alone (9.51 +/- 0.45). DKT at the dose of 360 mg/kg (GC = 3.77 +/- 0.10, P < 0.01) and 1,200 mg/kg (GC = 3.77 +/- 0.20, P < 0.01) significantly accelerated delayed GI transit induced by operation. Ondansetron, GR113,808, atropine, and truncal vagotomy abolished the stimulatory effect of DKT (360 mg/kg). When morphine was administered, GI transit was further reduced (GC = 1.97 +/- 0.10). DKT at the dose of 360 mg/kg (GC = 2.81 +/- 0.22, P < 0.05) and 1,200 mg/kg (GC = 2.87 +/- 0.23, P < 0.05) significantly improved delayed GI transit in morphine treated rats. CONCLUSIONS: DKT accelerates delayed GI transit induced by intestinal manipulation with and without concomitant morphine administration. DKT treatment may be useful for the patients with POI.
Intra-anal and rectal application of L-erythro methoxamine gel increases anal resting pressure in healthy volunteers.
Nisar PJ, Gruss HJ, Bush D, Barras N, Acheson AG, Scholefield JH
Br J Surg 2005 Oct 17;.
BACKGROUND: This study examined the effect of a single local application of L-erythro methoxamine, an alpha(1)-adrenoceptor agonist, on mean anal resting pressure (MARP) and cardiovascular variables in healthy volunteers. METHODS: L-Erythro methoxamine gel was administered in a single-blind manner; 0.3-3 per cent gels were applied perianally (n = 12), 1-3 per cent gels intra-anally (n = 16) and 1 per cent gel rectally (n = 8). MARP, systolic blood pressure, diastolic blood pressure and pulse rate were measured before application and for up to 6 h afterwards. Blood samples were taken to estimate plasma drug levels. RESULTS: Perianal gel produced no increase in MARP. Intra-anal 1 per cent and 3 per cent gel produced a significant rapid rise in MARP for 4 and 5 h respectively after application (P = 0.012 and P = 0.017 respectively). Rectal 1 per cent gel increased MARP for 2 h after application (P = 0.036). Intra-anal gel resulted in an increase in systolic blood pressure (1 per cent gel at 2 h, P = 0.042; 3 per cent gel at 4 h, P = 0.017). One per cent intra-anal and rectal gels caused a decrease in the pulse rate for 2 h after application (P = 0.012 and P = 0.018 respectively). Six subjects complained of nausea and three of headache after gel application. CONCLUSION: Intra-anal and rectal gel produced a sustained rise in MARP with rapid onset in volunteers. This raises the possibility of a therapeutic application for L-erythro methoxamine in patients with passive incontinence and internal anal sphincter dysfunction.
Anorectal motility responses to selective stimulation of the ventral sacral nerve roots in an experimental model.
Andersen IS, Rijkhoff NJ, Vukovic A, Buntzen S, Djurhuus JC, Laurberg S
Br J Surg 2005 Nov 4;.
BACKGROUND: Control of defaecation and continence may be lost in patients with spinal cord injury. Electrical stimulation of sacral nerve roots to promote defaecation simultaneously activates both the rectum and the external anal sphincter (EAS), and may actually obstruct defaecation. The aim of this study was to investigate whether the EAS could be blocked selectively by selective stimulation of the ventral sacral nerve roots, and whether activation of the rectum without activation of the EAS could be obtained by stimulation of the ventral sacral nerve roots. METHODS: Selective electrical stimulation was performed using anodal blocking, a tripolar cuff electrode and monophasic rectangular current pulses applied to the sacral nerve roots in nine Gottingen minipigs. RESULTS: Simultaneous responses in the rectum and the anal canal were observed in five animals, whereas only anal responses were noted in four. Variations in cross-sectional area and an increase in rectal pressure seemed to facilitate defaecation. Without blocking, the increase in anal canal pressure was 16-45 cmH(2)O. With blocking, this increase was abolished in seven and reduced to 3-6 cmH(2)O in two animals. CONCLUSION: Selective activation of the rectum is possible using an anodal block of somatic motor fibres. This technique holds promise in further development of electro-defaecation.
Rectal distension modulates canine gastric tone and accommodation.
Lei Y, Zhu H, Xing J, Chen JD
Dig Dis Sci 2005 Nov;50(11):2134-40.
Rectal distension affects upper GI myoelectrical activity and motility. The aim of this experiment was to investigate the effect of rectal distension on gastric tone, accommodation, and the underlying mechanism. Seven healthy dogs were surgically prepared and studied. Gastric tone and accommodation were assessed with a barostat. In Experiment 1, the effect of rectal distension on gastric tone and accommodation was evaluated; in Experiment 2, rectal distensions with various volumes were randomly applied and its effects on gastric tone were evaluated; and in Experiment 3, the role of the cholinergic pathway in distension-induced gastric relaxation was assessed. The results showed the following. (1) Rectal distension exerted an inhibitory effect on gastric tone, and this response was distension volume-dependent. (2) Postprandial gastric volume was similar in the control (468.6 +/- 24.7 ml) and the distension study (463.2 +/- 17.5 ml). However, rectal distension increased the preprandial gastric volume, and subsequently decreased the extent of gastric accommodation (139.3 +/- 34.7 ml), which was significantly lower than that of the control (383.2 +/- 26.3 ml; P < 0.001). (3) An intravenous bolus of atropine increased the astric volume from the baseline of 89.4 +/- 12.6 ml to 161.5 +/- 9.8 ml (P < 0.01), and subsequent rectal distension further increased this volume, but the overall change was comparable between the control (297.6 +/- 18.7 ml) and the atropine study (312.1 +/- 21.9 ml; P > 0.05). In conclusion, rectal distension inhibits gastric tone in a volume-dependent manner and impairs gastric accommodation. Atropine dose not block the effect of rectal distension on proximal gastric tone, suggesting that the observed effect may not be mediated by cholinergic pathway.
Segmental heterogeneity of electrogenic secretions in human ascending colon and rectum.
Park JH, Rhee PL, Lee JH, Kim JJ, Rhee JC, Kim SJ, Lee J
Int J Colorectal Dis 2005 Sep 13;:1-8.
AIMS: We have attempted to ascertain putative segmental differences in the secretory responses of the human ascending colon and rectum. METHODS: From the mucosal biopsy samples of two segments, the short-circuit current (I (sc)) and tissue resistance (R (te)) were compared under control conditions, as well as after the induction of secretion, using a modified Ussing chamber. We also performed semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) to detect and quantify transport proteins. RESULTS: The spontaneous I (sc) in the ascending colon was found to be greater than that in the rectum (P<0.01), whereas isobutylmethylxanthine/forskolin and carbachol (CCh) induced a greater rise in I (sc) in the rectum than in the ascending colon (P<0.05). When coupled with indomethacin pretreatment, the increase in DeltaI (sc) after the addition of CCh and forskolin was significant as compared to that observed without pretreatment (P<0.05). However, in the rectum, the secretory response to CCh and forskolin was abolished to a significant degree by indomethacin (P<0.05). Moreover, these indomethacin-induced changes were reversed by the addition of PGE2. Upon semiquantitative RT-PCR analysis, the amounts of cystic fibrosis transmembrane regulator, KCNQ1, and CLCA1 mRNAs were not found to be different between the two segments. CONCLUSION: There was a clear segmental heterogeneity with regard to electrogenic secretion in the human colon, and this difference can be explained by differences in the ascending colon and rectum.
The Location and Contents of the Lateral Ligaments of the Rectum: A Study in Human Soft Cadavers.
Pak-Art R, Tansatit T, Mingmalairaks C, Pattana-Arun J, Tansatit M, Vajrabukka T
Dis Colon Rectum 2005 Aug 29;.
PURPOSE: This study was designed to identify the location of the lateral ligaments of the rectum and to reveal its contents. METHODS: From 18 human soft cadavers (9 males), 18 pelves were sagittally sectioned into 36 hemipelvic specimens affording good anatomic view of the lateral aspect of the rectum. All of them were dissected and mobilized by using sharp technique under direct vision by one surgeon to avoid confounding factor. The lateral ligaments of the rectum were identified and the distances from the center of its pelvic attachment to the promontory of sacrum and coccyx were measured. After measurement, they were transected and brought for histologic examination. RESULTS: In 36 hemipelvic specimens, 18 lateral ligaments of the rectum were found on the right side of the rectum and 18 were found on the left side. One cadaver had no lateral ligament on the right side and another had two lateral ligaments on the right side 3-cm apart. The location of the lateral ligaments was posterolateral to the rectum. The distance from the lateral ligament to sacral promontory on right side was 8.14 +/- 1.82 cm (mean +/- standard deviation) and 8.14 +/- 1.22 cm on left side. The distances from the lateral ligament to coccyx on the right and left sides were 5.12 +/- 1.4 cm and 4.88 +/- 1.29 cm, respectively. The content of the lateral ligaments of the rectum consisted of loose connective tissue with cluster of small nerves. No artery was detected in all specimens. The small arterioles and venules were discovered in only four specimens. CONCLUSIONS: The lateral ligaments of the rectum were located at posterolateral side of the rectum. They were closer to the coccyx than to the sacral promontory. Its component was loose connective tissue containing multiple small nerves. There was no artery found in any lateral ligaments by histologic study. Small arterioles and venules were detected 11 percent.
Control of gastrointestinal motility by the "gut brain" - the enteric nervous system.
J Pediatr Gastroenterol Nutr 2005 Sep;41 Suppl 1:S4-6.
The enteric nervous system (ENS) as the "brain of the gut" is pivotal for normal muscle activity in the gut. Neuronal circuits within the ENS are designed to control gut motility independent of central inputs. To fulfill this task the ENS contains all necessary elements for coding mechanical and chemical stimuli, interneuronal communication and efferent output to the muscle. This review provides a summary of the ENS circuits that control muscle activity, the main transmitters and neuromodulators involved and the functional implications for the normal and diseased gut.
Stimulation of defecation: effects of coffee use and nicotine on rectal tone and visceral sensitivity.
Sloots CE, Felt-Bersma RJ, West RL, Kuipers EJ
Scand J Gastroenterol 2005 Jul;40(7):808-13.
OBJECTIVE: Coffee and cigarette use is believed to induce bowel movements, although the literature is controversial and precise measurements of rectal tone and sensitivity with a barostat have never been performed. The aim of this study was to assess the effects of coffee and nicotine on rectal tone, compliance and sensitivity. MATERIALS AND METHODS: Sixteen healthy volunteers were recruited for the coffee (n = 8) and nicotine (n = 8) experiments. The experiments were randomly performed in a placebo-controlled crossover design on separate days. In the coffee experiment, 280 ml strong coffee or warm water was drunk and in the nicotine experiment, nicotine (2 mg) or placebo was given sublingually. A rectal barostat procedure was carried out. A flaccid bag, mounted on a catheter, was inserted in the rectum. Continuous pressure distension was exerted to register basal visceral sensitivity and compliance. After rectal adaptation, the stimulus was given. Rectal tone was measured for 1 h, after which continuous pressure distension was repeated. RESULTS: Rectal tone increased by 45% 30 min after coffee intake (p = 0.031) and by 30% after water intake (p = 0.032), but the effects of coffee and water were not significantly different. Rectal tone did not change significantly after administration of nicotine (7%) or placebo (10%). There was no difference in compliance and visceral sensitivity between coffee and water or nicotine and placebo. CONCLUSIONS: Both coffee and warm water have an effect on defecation by increasing rectal tone, but nicotine (2 mg) did not affect rectal tone. Coffee and nicotine did not influence sensitivity or compliance.
The identification of specialized pacemaking cells in the anal sphincters.
Shafik A, El Sibai O, Ahmed I
Int J Colorectal Dis 2005 Aug 9;:1-5.
BACKGROUND AND AIMS: Interstitial cells of Cajal (ICC) are claimed to generate the electrical activity in the colon and stomach. As the external (EAS) and internal (IAS) anal sphincters exhibit resting electrical activity, we hypothesized the presence of ICC in these sphincters. This hypothesis was investigated in the current study. PATIENTS/METHODS: Specimens from the EAS and IAS were taken from normal areas of the anorectum which had been surgically excised by abdominoperineal operation for rectal cancer of 28 patients (16 men, 12 women, mean age 42.2+/-4.8 years). The specimens were subjected to c-kit immunohistochemistry. Controls for the specificity of the antisera consisted of tissue incubation with normal rabbit serum substituted for the primary antiserum. RESULTS/FINDINGS: Fusiform, c-kit positive, ICC-like cells were detected in the anal sphincters; they had dendritic processes. They were clearly distinguishable from the non-branching, c-kit negative smooth and striated muscle cells of the anal sphincters. The specimens contained also c-kit positive mast cells, but they had a rounded body with no dendritic processes. Immunoreactivity was absent in negative controls in which the primary antibody was omitted. INTERPRETATION/CONCLUSION: We have identified, for the first time, cells in EAS and IAS with morphological and immunological phenotypes similar to ICCs of the gut. These cells appear to be responsible for initiating the slow waves recorded from the anal sphincters and for controlling their activity. A deficiency or absence of these cells may affect the anal motile activity. Studies are needed to explore the role of these cells in anal motility disorders.
Extracorporeal Magnetic Stimulation of the Pelvic Floor: Impact on Anorectal Function and Physiology. A Pilot Study.
Thornton MJ, Kennedy ML, Lubowski DZ
Dis Colon Rectum 2005 Aug 18;.
PURPOSE: This study was designed to investigate the effect of extracorporeal magnetic stimulation on anorectal function and physiology. METHODS: A pilot study comparing the physiology of ten incontinent (9 females) and five continent (4 females) patients with and without perineal magnetic stimulation (10 Hz and 50 Hz) was performed. The ten incontinent patients were treated with two sessions weekly for five weeks of perineal magnetic stimulation. At treatment completion, precontinent and postcontinent scores and resting and squeeze anal pressure were compared. Patients also reported symptom improvement and satisfaction on a linear analog scale. RESULTS: The patients' mean age was 57 years. Sitting resting and squeeze anal pressures were significantly greater than lying pressures (P = 0.007, 0.047). Both 10-Hz and 50-Hz stimulation effected a significant increase in anal pressures compared with the baseline resting pressure (P = 0.005). The baseline squeeze pressures were significantly higher than the stimulated pressures compared with 50-Hz pressures (P = 0.022). After six weeks of treatment, there was a statistically significant increase in resting and squeeze anal pressures and a significant decrease in continence scores (P = 0.007, P = 0.008, P = 0.017). The mean percentage subjective improvement was 16 percent, and the mean patient satisfaction score was 3.3, positively correlating with an improvement in the continence score. CONCLUSIONS: Extracorporeal magnetic stimulation results in a significant increase in anal resting pressure irrespective of pretreatment continence. Although the subjective improvement in continence after treatment is small, there is a significant improvement in both resting pressures and patient continence scores.
Abstracts of the 20th International Symposium on Neurogastroenterology and Motility, Toulouse, France, 3-6 July 2005.
Neurogastroenterol Motil 2005 Aug;17 Suppl 2:1-85.
Gastrointestinal stem cells. II. Intestinal stem cells.
Bjerknes M, Cheng H
Am J Physiol Gastrointest Liver Physiol 2005 Sep;289(3):G381-7.
Epithelial cells and their neighbors. II. New perspectives on efferent signaling between brain, neuroendocrine cells, and gut epithelial cells.
Flemstrom G, Sjoblom M
Am J Physiol Gastrointest Liver Physiol 2005 Sep;289(3):G377-80.
Surface sensory enteroendocrine cells are established mucosal taste cells that monitor luminal contents and provide an important link in transfer of information from gut epithelium to the central nervous system. Recent studies now show that these cells can also mediate efferent signaling from the brain to the gut. Centrally elicited stimulation of vagal and sympathetic pathways induces release of melatonin, which acts at MT2 receptors to increase mucosal electrolyte secretion. Psychological factors as well mucosal endocrine cell hyperplasia are implicated in functional intestinal disorders. Central nervous influence on the release of transmitters from gut endocrine cells offers an exciting area of future gastrointestinal research with a clinical relevance.
What is the optimum methodology for the clinical measurement of resting anal sphincter pressure?
Prott G, Hansen R, Badcock C, Kellow J, Malcolm A
Neurogastroenterol Motil 2005 Aug;17(4):595-9.
Abstract There are conflicting recommendations from consensus groups with regard to the assessment of resting anal sphincter pressure. Our aims were to evaluate and compare the performance of three recognized techniques for the clinical measurement of resting anal sphincter pressure. Methods: In each of 54 patients presenting for anorectal manometry, and suffering from constipation or fecal incontinence, three different techniques for assessment of resting anal pressure were undertaken, namely stationary, stationary pull-through and slow pull-through techniques. Resting anal sphincter pressures were compared between groups and between techniques. Results: Mean resting anal sphincter pressure was lower with stationary, compared with stationary pull-through and slow pull-through, techniques (P </= 0.002). Resting pressure was higher for constipation than incontinence regardless of technique used (P < 0.00001). The techniques were highly correlated with each other (P < 0.0001). The stationary pull-through technique conferred a minor advantage in the discrimination between constipation and incontinence. The stationary technique required significantly less time for completion (P < 0.0001). Conclusion: Resting anal sphincter pressure varies according to the specific technique employed, yet each technique is valid. The stationary pull-through technique confers a minor advantage in clinical discrimination of patients, but the stationary technique is more time-efficient. Standardized anal sphincter testing should be established to enable inter-laboratory comparisons.
Neural and non-neural mediation of propionate-induced contractile responses in the rat distal colon.
Mitsui R, Ono S, Karaki S, Kuwahara A
Neurogastroenterol Motil 2005 Aug;17(4):585-94.
Differential expression of P2X-purinoceptor subtypes in circular and longitudinal muscle of canine colon.
Lee HK, Ro S, Kathy KD, Kim YH, Kim HW, Horowitz B, Sanders KM
Neurogastroenterol Motil 2005 Aug;17(4):575-84.
Perceptual sensitivity and response bias during rectal distension in patients with irritable bowel syndrome.
Corsetti M, Ogliari C, Marino B, Basilisco G
Neurogastroenterol Motil 2005 Aug;17(4):541-7.
Abstract Patients with irritable bowel syndrome (IBS) report an increased frequency of sensations during rectal distension in comparison with healthy subjects. This alteration might be due to a psychological response bias leading patients to over report their sensations. The aim of this study was to measure perceptual sensitivity and response bias during rectal distension in healthy subjects and IBS patients using the sensory decision theory (SDT). Thirteen healthy subjects and 22 IBS patients underwent five rectal distensions up to 100 mL, five up to 200 mL and five sham distensions. They were asked to identify the distension by means of an electronic marker. Perceptual sensitivity and response bias were calculated according to the SDT. The patients identified a more 100 mL distensions than the healthy subjects (P = 0.02), whereas there was no difference in the number of identified 200 mL and sham distensions between the two groups. The perceptual sensitivity of IBS patients was significantly greater during 100 mL (P = 0.01), but not during 200 mL distensions. The response bias was not significantly different between the two groups. These data suggest that the increased frequency of sensations reported by IBS patients is not due to a psychological response bias.
Central cholecystokinin activity in irritable bowel syndrome, panic disorder, and healthy controls.
Koszycki D, Torres S, Swain JE, Bradwejn J
Psychosom Med 2005 Jul-Aug;67(4):590-5.
OBJECTIVE: Irritable bowel syndrome (IBS) and panic disorder (PD) coexist with a high frequency. However, the nature of this relationship remains obscure. We have proposed that PD and IBS may share a common dysfunction of the central cholecystokinin (CCK) system. To test this hypothesis, we assessed whether the enhanced panicogenic response to CCK-tetrapeptide (CCK-4) observed in PD is also present in IBS. METHODS: Eight psychiatrically healthy IBS patients, 8 PD patients with no history of IBS, and 12 normal controls received a bolus injection of CCK-4 and placebo on two separate days in a double-blind, randomized fashion. RESULTS: Consistent with previous findings, panicogenic sensitivity to CCK-4 was enhanced in PD patients relative to controls. In contrast, IBS patients exhibited a response that was comparable to controls. Interestingly, CCK-4-induced nausea and abdominal distress were decreased in IBS patients relative to the other groups. No diagnostic difference was noted for cardiovascular response to CCK-4. CONCLUSION: These data indicate that IBS patients with no lifetime psychiatric history do not share the CCK-2 receptor dysfunction implicated in the pathophysiology of PD and that this dysfunction may not be a common mechanism for both CNS and enteric nervous system disorders. Nevertheless, the results suggest that a dysfunction of the CCK system may be involved in the pathophysiology of some enteric symptoms associated with IBS.
Colon motility during a panic attack.
Hyman PE, Cocjin J
Psychosom Med 2005 Jul-Aug;67(4):616-7.
OBJECTIVE: To document the temporal relationship between a panic attack and high amplitude propagating contractions. METHODS: Colon manometry was used to discriminate between functional defecation problems and colon neuromuscular disease. By chance, the patent developed a panic attack during the test session. RESULTS: Coincident with the panic attack, there was a continuous series of high amplitude propagating contractions. There were 15 high amplitude propagating contractions over 45 minutes, initially at a rate of 4 per 10 minutes, gradually slowing to 1.5 per 10 minutes. CONCLUSIONS: These data may explain the cause for gastrointestinal distress and diarrhea in some patients with panic attacks.
Sitz Bath: Where Is the Evidence? Scientific Basis of a Common Practice.
Tejirian T, Abbas MA
Dis Colon Rectum 2005 Jun 16;.
PURPOSE: This study was designed to determine if evidence exists to justify and support the recommendation of sitz bath in the management of anorectal disorders. METHODS: A Medline search was conducted using the key words "sitz bath" and "hot bath." RESULTS: Thirty-six articles were found which highlighted the physiology, benefits, risks, complications, and techniques of sitz bath. Most of the studies were published in gynecologic or nursing journals. One randomized study comparing sitz bath to placebo was found. Two articles speculated that sitz bath induces relaxation of the internal sphincter muscle. Cold sitz bath was reported to decrease perineal edema more than warm sitz bath, although patients tended to prefer the latter. Five articles reported complications of sitz bath, including dissemination of herpes, maternal-neonatal Streptococcus outbreak, and skin burns. CONCLUSION: A review of the literature demonstrated a lack of scientific data to support the use of sitz bath in the treatment of anorectal disorders. Additional randomized and controlled clinical studies are needed to investigate whether this time consuming recommendation is beneficial to patients.
VSL#3 Probiotic-Mixture Induces Remission in Patients with Active Ulcerative Colitis.
Bibiloni R, Fedorak RN, Tannock GW, Madsen KL, Gionchetti P, Campieri M, De Simone C, Sartor RB
Am J Gastroenterol 2005 Jul;100(7):1539-46.
BACKGROUND AND AIMS: Intestinal bacteria have been implicated in the initiation and perpetuation of IBD; in contrast, "probiotic bacteria" have properties possibly effective in treating and preventing relapse of IBD. We evaluated the safety and efficacy of VSL#3 and the components, and the composition of the biopsy-associated microbiota in patients with active mild to moderate ulcerative colitis (UC). METHODS: Thirty-four ambulatory patients with active UC received open label VSL#3, 3,600 billion bacteria daily in two divided doses for 6 wk. The presence of biopsy-associated bacteria was detected using a nucleic acid-based method and the presence of VSL#3 species confirmed by DNA sequencing of 16S rRNA. RESULTS: Thirty-two patients completed 6 wk of VSL#3 treatment and 2 patients did not have the final endoscopic assessment. Intent to treat analysis demonstrated remission (UCDAI </= 2) in 53% (n = 18); response (decrease in UCDAI >/= 3, but final score >/=3) in 24% (n = 8); no response in 9% (n = 3); worsening in 9% (n = 3); and failure to complete the final sigmoidoscopy assessment in 5% (n = 2). There were no biochemical or clinical adverse events related to VSL#3. Two of the components of VSL#3 were detected by PCR/DGGE in biopsies collected from 3 patients in remission. CONCLUSION: Treatment of patients with mild to moderate UC, not responding to conventional therapy, with VSL#3 resulted in a combined induction of remission/response rate of 77% with no adverse events. At least some of the bacterial species incorporated in the probiotic product reached the target site in amounts that could be detected. (Am J Gastroenterol 2005;100:1539-1546).
Propulsive activity induced by sequential electrical stimulation in the descending colon of the pig.
Sevcencu C, Rijkhoff NJ, Gregersen H, Sinkjaer T
Neurogastroenterol Motil 2005 Jun;17(3):376-87.
This work was performed to study electrically induced contractions in the descending colon of pigs. Contractions were monitored using impedance planimetry and manometry. The luminal pressure, cross-sectional area (CSA), latency and velocity of CSA decrease were compared when using 3 ms, 9, 12, 15 or 30 mA pulses at 10 Hz for 10 s, and 15 mA, 0.03, 0.3 or 3 ms pulses at 10 Hz for 10 s. Stimulation was performed prior and after the application of N(G)-nitro-L-arginine methyl ester (L-NAME) and atropine. In the untreated colon, contraction was always of an 'off' type. A current increase from 9 to 30 mA increased the pressure. An increase of pulse duration from 0.03 to 3 ms shortened the latency, accelerated contraction and increased pressure. By sequential stimulation, contractions were coordinated to propel semi-fluid and solid luminal contents. L-NAME increased the magnitude of CSA decrease. Atropine induced inhibitory effects on contractions elicited by 3 ms pulses and abolished contractions induced by 0.03 and 0.3 ms pulses. In conclusion: (i) electrical stimulation evokes'off' colon contractions, which can be coordinated to result in propulsion; (ii) the best combination for current and pulse duration to induce propulsive contractions is 15 mA and 3 ms; (iii) nitrergic and cholinergic pathways mediate responses to electrical stimulation.
Inhibitory Effects of Sildenafil Citrate on the Tonus of Isolated Dog Internal Anal Sphincter.
Aygen E, Camci C, Durmus AS, Dogru O, Topuz O, Ayten R, Ayar A.
Dis Colon Rectum 2005 May 26;
PURPOSE: Although the exact pathogenesis of anal fissure is not known, hypertonicity of the internal anal sphincter might be involved in its pathogenesis as main event. To gain information about possible usefulness of the novel, smooth-muscle-relaxing drug, sildenafil, in chronic anal fissure, we investigated the effect of sildenafil citrate on acetylcholine-induced contractility of internal anal sphincter isolated from dogs. METHODS: Internal anal sphincter strips were taken from German shepherd dogs and suspended in a tissue bath filled with Krebs solution at 37 degrees C (pH 7.4) continuously bubbled with 95 percent oxygen and 5 percent carbon dioxide, and isometric contractions were recorded. Contractions were evoked by 10 muM acetylcholine, and the effects of different concentrations of sildenafil citrate (0.1, 0.3, and 1 mM) on the isometric tension of each internal anal sphincter strip were examined. The statistical significance was analyzed by one-way analysis of variance. RESULTS: Pretreatment with sildenafil citrate (0.1 mM) attenuated contractile response to acetylcholine (n = 3), which were significantly weak compared with the maximum contractile response to the acetylcholine alone (610 +/- 110 mg vs. 2,825.17 +/- 416 mg; n = 12; P < 0.05). Sildenafil citrate also significantly inhibited the acetylcholine-induced contractions in a dose-dependent manner when applied after. CONCLUSIONS: This experimental in vitro study showed that sildenafil citrate relaxes acetylcholine stimulated contractions of isolated dog internal anal sphincter. This may be of importance for raising the possibility that sildenafil cit-rate may have future potential in the treatment of chronic anal fissure. Further studies are needed for a conclusive decision on possible usefulness of sildenafil citrate in patients with chronic anal fissure.
Contribution of the pudendal nerve to sensation of the distal rectum.
Chan CL, Ponsford S, Scott SM, Swash M, Lunniss PJ.
Br J Surg 2005 May 16;
BACKGROUND: Anal and rectal sensory mechanisms and pudendal nerve function are important in the control of faecal continence. The contribution of the pudendal nerve to sensation of the distal rectum was investigated. METHODS: Heat thresholds in the anal canal, distal and mid rectum were measured using a specially designed thermoprobe. Rectal sensory threshold volumes were measured using the balloon distension method. Needle electrodes were inserted into the external anal sphincter. Pudendal nerve block was performed through a perineal approach, and completeness assessed by loss of electromyographic activity. Heat and rectal volume thresholds were measured again following unilateral and bilateral pudendal nerve block. RESULTS: The technique was successful in four of six volunteers. Bilateral pudendal nerve block produced complete anaesthesia to heat in the anal canal (P = 0.029), but had no effect on heat thresholds in the distal or mid rectum. Rectal sensory threshold volumes were also unaffected by pudendal nerve anaesthesia. CONCLUSION: Anal canal sensation is subserved by the pudendal nerve, but this nerve is not essential to nociceptive sensory mechanisms in the distal or mid rectum. The transition between visceral control mechanisms in the lower rectum and somatic mechanisms in the anal canal may have functional importance in the initiation of defaecation and the maintenance of continence. Copyright (c) 2005 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.
Rectocolonic Excitatory Reflex or Rectocolonic Inhibitory Reflex?
Dis Colon Rectum 2005 May 26;
5-HT4 receptors located on cholinergic nerves in human colon circular muscle. Leclere PG, Prins NH, Schuurkes JA, Lefebvre RA. Neurogastroenterol Motil 2005 Jun;17(3):366-75.
5-Hydroxytryptamine 4 (5-HT4) receptor agonists promote colonic propulsion. The alteration of circular muscle (CM) motility underlying this involves inhibition of contractility via smooth muscle 5-HT4 receptors and proximal colonic motility stimulation, the mechanism of the latter not having been characterized. Our aim was to identify and characterize a 5-HT4 receptor-mediated stimulation of human colon CM contractile activity. 5-HT4 receptor ligands were tested on electrical field stimulation (EFS)-induced contractions of human colonic muscle strips cut in the circular direction (called 'whole tissue' strips). Additionally, after incubation of tissues with [3H]-choline these compounds were tested on EFS-induced release of tritium in whole tissue strips and in 'isolated' CM strips, obtained by superficial cutting in the CM layer. Tetrodotoxin and atropine blocked EFS-induced contractions of whole tissue CM strips. Prucalopride (0.3 micromol L-1) evoked a heterogenous response on EFS-induced contraction, ranging from inhibition (most frequently observed) to enhancement. In the release experiments, EFS-induced tritium efflux was blocked by tetrodotoxin. Prucalopride increased EFS-induced tritium and [3H]-acetylcholine efflux in whole tissue and in isolated CM strips. All effects of prucalopride were antagonized by the selective 5-HT4 receptor antagonist GR113808. The results obtained indicate the presence of excitatory 5-HT4 receptors on cholinergic nerves within the CM of human colon.
N-Methyl-d-Aspartate Receptors Mediate Endogenous Opioid Release in Enteric Neurons After Abdominal Surgery.
Patierno S, Zellalem W, Ho A, Parsons CG, Lloyd KC, Tonini M, Sternini C.
Gastroenterology 2005 Jun;128(7):2009-19.
Background & Aims: We tested the hypothesis that N -methyl- d -aspartate (NMDA) receptors mediate surgery-induced opioid release in enteric neurons. Methods: We used mu opioid receptor (muOR) internalization as a measure of opioid release with immunohistochemistry and confocal microscopy. muOR internalization was quantified in enteric neurons from nondenervated and denervated ileal segments of guinea pig after abdominal laparotomy with and without pretreatment with NMDA-receptor antagonists acting at different recognition sites (+)-5-methyl-10, 11-dihydro-5H-dibenzo [ a , b ] cyclohepten-5, 10-imine (MK-801) or (D) 2-amino-5-phosphopenoic acid (AP-5) at .5, 1 mg/kg; 8-chloro-4-hydroxy-1-oxo-1, 2-dihydropyridazinol [4,5-]quinoline-5-oxide choline (MRZ 2/576) or 8-chloro-1, 4-dioxo-1,2,3,4-tetrahydropyridazinol [4,5-]quinoline choline salt (MRZ 2/596) at .3, 1 mg/kg, or with an antagonist for the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, 6-cyano-7-nitroquinoxaline-2, 3-dione (1, 3 mg/kg). To determine whether NMDA stimulation induces opioid release, (1) ilea were exposed to NMDA (100 mumol/L) and D-serine (10 mumol/L) with or without the antagonist MK-801 or AP-5 (50 mumol/L); and (2) neuromuscular preparations of the ileum were stimulated electrically (20 Hz, 20 min) with or without MK-801 or AP-5 (50 mumol/L). Results: muOR endocytosis induced by abdominal laparotomy was inhibited significantly by NMDA-receptor antagonists in nondenervated and denervated ileal segments, but not by the AMPA-receptor antagonist. muOR endocytosis in neurons exposed to NMDA or electrical stimulation was prevented by NMDA-R antagonists. Conclusions: Abdominal laparotomy evokes local release of glutamate that results in endogenous opioid release through the activation of peripheral NMDA receptors. This suggests an interaction between the glutamatergic and opioid systems in response to the noxious and perhaps mechanosensory stimulation of surgery.
Rectal instillation of butyrate provides a novel clinically relevant model of noninflammatory colonic hypersensitivity in rats.
Bourdu S, Dapoigny M, Chapuy E, Artigue F, Vasson MP, Dechelotte P, Bommelaer G, Eschalier A, Ardid D.
Gastroenterology 2005 Jun;128(7):1996-2008.
Background & Aims: The treatment of irritable bowel syndrome (IBS), characterized by abdominal pain and bloating, is empirical and often poorly efficient. Research lacks suitable models for studying the pathophysiologic mechanisms of the colonic hypersensitivity and new pharmacologic targets. The present study aimed to develop a novel model of colonic hypersensitivity possessing several of the characteristics encountered in patients with IBS. Methods: Rats received enemas of a butyrate solution (8-1000 mmol/L) twice daily for 3 days. A time course was determined for colonic hypersensitivity (colorectal distention test) and referred cutaneous lumbar hyperalgesia (von Frey hairs). Macroscopic and histologic analyses were performed on colonic mucosa. The efficacy of morphine, U50488H (a kappa opioid agonist), and trimebutine on the 2 pain parameters was determined. Finally, the involvement of peptidergic C-fibers was evaluated using capsaicin-pretreated animals and treatments with calcitonin gene-related peptide (CGRP) and neurokinin 1 receptor antagonists. Results: Butyrate enemas induced a sustained, concentration-dependent colonic hypersensitivity and, to a lesser extent, a referred cutaneous mechanical hyperalgesia, particularly in female rats, but no macroscopic and histologic modifications of the colonic mucosa, as observed in patients with IBS. Both pain parameters were sensitive to morphine, U50488H, trimebutine, neonatal capsaicin treatment, and the CGRP receptor antagonist but not to the neurokinin 1 receptor antagonist. Conclusions: These results present our noninflammatory model of chronic colonic hypersensitivity as a useful novel tool for studying IBS. The CGRP receptor antagonist-induced reduction of colonic hypersensitivity suggests that CGRP receptors may provide a promising target for treatment of IBS.
A regenerative role for bone marrow following experimental colitis: contribution to neovasculogenesis and myofibroblasts.
Brittan M, Chance V, Elia G, Poulsom R, Alison MR, Macdonald TT, Wright NA.
Gastroenterology 2005 Jun;128(7):1984-95.
Background & Aims: Bone marrow (BM) cells form differentiated adult lineages within nonhematopoietic tissues, with a heightened propensity with increasing regenerative pressure dictated by disease. We have previously shown that BM cells engraft into the gut and contribute substantially to the subepithelial intestinal myofibroblast population in the lamina propria. To investigate the reparative capacity of BM in inflammatory bowel disease (IBD), a well-established model of experimental colitis was used. Methods: Lethally irradiated female mice were rescued by a BM transplant from male donors. Colitis was induced 6 weeks posttransplantation by injection of trinitrobenzene sulfonic acid (TNBS), and tissues were analyzed 1-14 days later. Donor-derived cells were detected by in situ hybridization using a Y chromosome-specific probe, and their phenotype was determined by immunohistochemistry. Results: TNBS-induced colitis was manifest as patchy lesions that increased in severity between days 1 and 8, and the mucosa gradually regenerated between days 8 and 14. The contribution of BM to intestinal myofibroblasts was significantly increased in regions of colitis compared with noninflamed regions. Furthermore, BM-derived endothelial cells, pericytes, and vascular smooth muscle cells were frequently interspersed throughout blood vessels, suggesting that these cells facilitate angiogenesis in tissue repair, substantiated by a significant increase in the incidence of BM-derived vascular smooth muscle cells in colitic compared with noninflamed regions. Blood vessels formed entirely from BM-derived cells were also seen, suggesting a role for BM in neovasculogenesis. Conclusions: Our data show that BM contributes to multiple intestinal cell lineages in colitis, with an important function in tissue regeneration and vasculogenesis after injury.
Role of cyclooxygenases 1 and 2 in the modulation of neuromuscular functions in the distal colon of humans and mice.
Fornai M, Blandizzi C, Colucci R, Antonioli L, Bernardini N, Segnani C, Baragatti B, Barogi S, Berti P, Spisni R, Del Tacca M
Gut 2005 May;54(5):608-16.
BACKGROUND: Cyclooxygenase isoforms (COX-1, COX-2) may exert differential regulatory actions on enteric motor functions under normal or pathological conditions. AIMS: To examine the occurrence and functions of COX-1 and COX-2 in the neuromuscular compartment of normal distal colon using human and murine tissue. METHODS: Gene expression (human, mouse), protein expression (human), gene deletion (mouse), and the effects of dual and isoform specific COX inhibitors on in vitro motility (human, mouse) were investigated. RESULTS: Reverse transcription-polymerase chain reaction (RT-PCR) showed mRNA expression of COX-1 and COX-2 in human and wild-type mouse colonic muscle whereas only COX-2 or COX-1 was detected in COX-1 or COX-2 knockout animals. Immunohistochemistry localised both isoforms in neurones of myenteric ganglia, COX-1 in circular layer myocytes, and COX-2 in longitudinal muscle. Indomethacin (COX-1/COX-2 inhibitor), SC-560 (COX-1 inhibitor), or DFU (COX-2 inhibitor) enhanced atropine sensitive electrically induced contractions of human longitudinal muscle. The most prominent actions were recorded with indomethacin or SC-560 plus DFU. These results were confirmed under pharmacological blockade of non-cholinergic nerves. Atropine sensitive contractions evoked by carbachol in the presence of tetrodotoxin were enhanced by indomethacin or DFU but not by SC-560. In wild-type mice, contractile responses to electrical stimulation were enhanced by indomethacin, SC-560, or DFU. SC-560 potentiated electrically induced contractions in COX-2, but not COX-1, knockout mice. In contrast, DFU enhanced the contractions elicited by electrical stimuli in COX-1, but not in COX-2, knockout mice. CONCLUSIONS: These results indicate that COX-1 and COX-2 are expressed in the neuromuscular compartment of normal human colon where they modulate cholinergic excitatory control of colonic motility at prejunctional and postjunctional sites, respectively.
The Development of a Validated Instrument to Evaluate Bowel Function After Sphincter-Preserving Surgery for Rectal Cancer.
Temple LK, Bacik J, Savatta SG, Gottesman L, Paty PB, Weiser MR, Guillem JG, Minsky BD, Kalman M, Thaler HT, Schrag D, Wong WD
Dis Colon Rectum 2005 Apr 14;
PURPOSE: Sphincter-preserving surgery is technically feasible for many rectal cancers, but functional results are not well understood. Therefore, the purpose of this study was to develop an instrument to evaluate bowel function after sphincter-preserving surgery. METHODS: A 41-item bowel function survey was developed from a literature review, expert opinions, and 59 patient interviews. An additional 184 patients who underwent sphincter-preserving surgery between 1997 and 2001 were asked to complete the survey and quality-of-life instruments (Fecal Incontinence Quality of Life, European Organization for Research and Treatment of Cancer QLQ 30/Colorectal Cancer 38). A factor analysis of variance was performed. Test-retest reliability was evaluated, with 20 patients completing two surveys within a mean of 11 days. Validity testing was done with clinical variables (gender, age, radiation, length of time from surgery), surgical variables (procedure: local excision, low anterior resection, coloanal anastomosis), reconstruction (J-pouch, straight), anastomosis (handsewn, stapled), and quality-of-life instruments. RESULTS: The survey response rate was 70.1 percent (129/184). Among the 127 patients with usable data, 67 percent were male, the median age was 64 (range, 38-87) years, and the mean time for restoration of bowel continuity after sphincter-preserving surgery was 22.9 months. Patients had a median of 3.5 stools/day (range, 0-30), and 37 percent were dissatisfied with their bowel function. Patients experienced a median of 22 symptoms (range, 7-32), with 27 percent reported as severe, 37 percent as moderate, and 36 percent as mild. The five most common symptoms were incomplete evacuation (96.8 percent), clustering (94.4 percent), food affecting frequency (93.2 percent), unformed stool (92.8 percent), and gas incontinence (91.8 percent). The factor analysis identified 14 items that collapsed into three subscales: FREQUENCY (alpha = 0.75), DIETARY (alpha = 0.78), and SOILAGE (alpha = 0.79), with acceptable test-retest reliability for the three subscales and total score (0.62-0.87). The instrument detected differences between patients with preoperative radiation (n = 67) vs. postoperative radiation (n = 15) vs. no radiation (n = 45) (P = 0.02); local excision (n = 10) vs. low anterior resection (n = 55) vs. coloanal anastomosis (n = 62) (P = 0.002); and handsewn (n = 18) vs. stapled anastomosis (n = 99) (P = 0.006). The total score correlated with 4 of 4 Fecal Incontinence Quality of Life (P < 0.01) and 9 of 17 European Organization for Research and Treatment of Cancer subscales (all P < 0.01). CONCLUSIONS: Patients undergoing sphincter-preserving surgery for rectal cancer have impaired bowel function, and those treated with radiation, coloanal anastomoses, or handsewn anastomoses have significantly worse function. This reliable and valid instrument should be used to prospectively evaluate bowel function after sphincter-preserving surgery in patients undergoing rectal cancer therapy.
A 5-HT4 agonist, mosapride enhances intrinsic recto-rectal and recto-anal reflexes after removal of extrinsic nerves in guinea pigs.
Kojima Y, Nakagawa T, Katsui R, Fujii H, Nakajima Y, Takaki M
Am J Physiol Gastrointest Liver Physiol 2005 Apr 7;
Distension-evoked reflex rectal (R-R) contractions and internal anal sphincter (R-IAS) relaxations can be generated in guinea pigs through an extrinsic sacral excitatory neural pathway (pelvic nerves) as well as intrinsic cholinergic excitatory and nitrergic inhibitory pathways. The aim of the present study was to create intrinsic R-R and R-IAS reflex models by destruction of the lumbar and sacral cords (PITH) and evaluate whether the prokinetic benzamide, mosapride, a 5-HT4 receptor agonist, enhances these reflexes. The mechanical activities of the R-R and R-IAS were recorded in the anesthetized guinea pig on 2- 9th day after PITH. Although the basal rectal pressure at distension after PITH was significantly lower than control, the reflex indexes of R-R contractions and synchronous R-IAS relaxations were unchanged between 4-9 days after PITH. The frequency of spontaneous rectal and IAS motility were also unchanged. Immunohistochemical studies revealed that the distribution of myenteric and intramuscular interstitial cells of Cajal were not altered after PITH. Mosapride (0.1-1.0 mg/kg IV) dose-dependently increased both intrinsic R-R (maximum: 1.82) and R-IAS reflex indexes (maximum: 2.76) from control (1.0) 6-9 days after PITH. The 5-HT4 receptor antagonist, GR 113808 1.0 mg/kg IV decreased the R-R and R-IAS reflex indexes by approximately 50% and antagonized the effect of mosapride 1.0 mg/kg IV. The present results indicate that mosapride moderately enhanced intrinsic R-R and R-IAS reflexes functionally compensated after deprivation of extrinsic nerves, mediated through endogenously active, intrinsic 5-HT4 receptors.
Development of a 3-Dimensional Physiological Model of the Internal Anal Sphincter Bioengineered in-vitro from Isolated Smooth Muscle Cells.
Hecker L, Baar K, Dennis RG, Bitar KN
Am J Physiol Gastrointest Liver Physiol 2005 Mar 17;
Background: Fecal incontinence affects people of all ages and social backgrounds and can have devastating psychological and economic consequences. This disorder is largely attributed to decreased mechanical efficiency of the internal anal sphincter (IAS), yet little is known about the pathophysiological mechanisms responsible for the malfunction of sphincteric smooth muscle at the cellular level. Objective: To develop a 3- Dimensional Physiological Model of the IAS Bioengineered in-vitro from Isolated Smooth Muscle Cells. Methods: Smooth muscle cells isolated from the IAS of rabbits were seeded in culture on top of a loose fibrin gel, where they migrated and self-assembled in circumferential alignment. As the cells proliferated, the fibrin gel contracted around a 5mm diameter SYLGARD mold, resulting in a 3-D cylindrical ring of sphincteric tissue. Results: 1) The bioengineered IAS rings generated a spontaneous basal tone. 2) Stimulation with 8-br-cAMP caused a sustained decrease in the basal tone (relaxation), which was calcium-independent. 3) Upon stimulation with acetylcholine, bioengineered IAS rings showed a calcium and concentration-dependent peak contraction at 30 seconds, which was sustained for 4 minutes. 4) Addition of 8-br-cAMP-induced rapid relaxation of acetylcholine-induced contraction and force generation of IAS rings. 5) Lastly, bioengineered sphincter rings show striking functional differences when compared to bioengineered rings made from isolated colonic smooth muscle cells. Conclusions: This is the first report of a 3-D in-vitro model of a gastrointestinal smooth muscle IAS. Bioengineered IAS rings demonstrate physiological functionality and may be used in the elucidation of the mechanisms causing sphincter malfunction.
Impact of prebiotics and probiotics on enteric flora.
de Simone C
J Pediatr Gastroenterol Nutr 2005 Apr;40 Suppl:S40.
Colorectal Inflammation is Well Predicted by Fecal Calprotectin in Children with Gastrointestinal Symptoms.
Fagerberg UL, Loof L, Myrdal U, Hansson LO, Finkel Y
J Pediatr Gastroenterol Nutr 2005 Apr;40(4):450-455.
OBJECTIVES: The protein calprotectin is mainly derived from neutrophils. Increased fecal excretion of calprotectin has been reported in inflammatory bowel disease. The recommended cut-off level in adults (<50 mug/g feces) seems to be applicable in children aged 4 to 17 years. The aim of this study was to evaluate the use of fecal calprotectin to detect colorectal inflammation in children with gastrointestinal symptoms. METHODS: We obtained stool samples on thirty-six children with gastrointestinal symptoms and suspected inflammation of the colon before they underwent colonoscopy. The samples were examined with an improved fecal calprotectin enzyme-linked immunosorbent assay method (Calprest(R), Eurospital). The results were correlated with the histopathologic findings in the colon. RESULTS: In children with colorectal inflammation (n = 22) the median fecal calprotectin concentration was 349 mug/g (range, 15.4-1860 mug/g). The most common diagnosis in this group was inflammatory bowel disease. Median fecal calprotectin was 16.5 mug/g (range, 5.0-65 mug/g) in children with no inflammation (n = 14). When <50 mug/g was used as upper reference limit the fecal calprotectin test had a sensitivity of 95%, specificity 93%, positive predictive value 95% and negative predictive value 93% to detect colorectal inflammation. CONCLUSIONS: The improved fecal calprotectin enzyme-linked immunosorbent assay is a simple test with potential use in children. Increased fecal calprotectin strongly predicted the presence of colorectal inflammation in children with gastrointestinal symptoms. Fecal calprotectin can be used to select patients who should undergo diagnostic colonoscopy for investigation of colorectal inflammation, including inflammatory bowel disease.
Assessment of the Rectoanal Inhibitory Reflex in Preterm Infants with Delayed Meconium Passage.
Lorijn FD, Voskuijl WP, Omari TI, Kok JH, Taminiau JA, Benninga MA
J Pediatr Gastroenterol Nutr 2005 Apr;40(4):434-437.
BACKGROUND: There is an inverse relationship between gestational age, birth weight and the time of first neonatal bowel movement. The authors hypothesized that delayed passage of meconium might result from a delayed maturation of the recto-anal inhibitory reflex (RAIR) in premature infants. OBJECTIVE: To evaluate whether the RAIR is absent in very preterm infants 28-32 weeks postmenstrual age with delayed meconium production. STUDY DESIGN: Anorectal manometry was performed in 10 preterm infants (seven male) with delayed meconium production (no meconium in the first 48 hours). Median postmenstrual age was 30 weeks (28-31 weeks). Birth weight ranged from 780 to 1930 g (median, 1395 g). A micromanometric assembly (outer diameter, 2.0 mm) was used which incorporated a 1.5-cm-long sleeve sensor for measurement of resting anal sphincter pressure and relaxation. Four side-holes recorded anal and rectal pressures. Rectal distension was performed with direct air insufflation to elicit the RAIR. RESULTS: The time from birth to passage of meconium ranged from 48 to 105 hours (median, 82 hours). The mean anal sphincter pressure, rectal pressure, and anal sphincter oscillation frequency were 22.0 +/- 5.0 mm Hg, 6.9 +/- 2.0 mm Hg, and 9.8 +/- 1.9/min, respectively. A normal RAIR was elicited in all infants. CONCLUSION: Anorectal manometry recordings in premature infants with delayed passage of meconium showed normal anorectal pressures and a normal RAIR, suggesting that delayed meconium passage is not related to the absence of a RAIR.
Treatment of Chronic Anal Fissure by Application of L: -Arginine Gel: A Phase II Study in 15 Patients.
Gosselink MP, Darby M, Zimmerman DD, Gruss HJ, Schouten WR
Dis Colon Rectum 2005 Mar 2;.
PURPOSE: Local application of exogenous nitric oxide donors, such as isosorbide dinitrate and glyceryl trinitrate, promotes fissure healing by reducing anal resting pressure and improving anodermal blood flow. The major drawback of these nitric oxide donors is headache. The overall incidence of this side effect is approximately 40 percent. Recently we have shown in healthy volunteers that L: -arginine, being an intrinsic precursor of nitric oxide, reduces anal resting pressure without headache as a side effect. The aim of the pres-ent study was to evaluate the effect of L: -arginine on anal resting pressure, anodermal blood flow, and fissure healing in patients with chronic anal fissure. METHODS: Fifteen patients with a chronic anal fissure were included in the present study. Before entering the study 10 patients were unsuccessfully treated by local application of isosorbide dinitrate. Six of these patients experienced severe headache during treatment with isosorbide dinitrate. All patients were treated for at least 12 weeks by local application of a gel containing L: -arginine 400 mg/ml five times a day. In patients with a persistent fissure, treatment was continued until 18 weeks. Anal manometry and laser Doppler flowmetry of the anoderm were performed before treatment, 20 minutes after local application of the first dose, and after 12 weeks of treatment. A visual analog scale was used to assess fissure-related pain and headache. RESULTS: One patient dropped out after one day of treatment, and one was excluded because of violation of the study protocol. After 12 weeks of treatment complete fissure healing was observed in 3 of 13 (23 percent) patients, and after 18 weeks the healing rate was 8 of 13 (62 percent) patients. None of the 13 patients experienced typical nitric oxide-induced headache. The pressure recordings showed a significant reduction of maximum anal resting pressure (mean +/- SD): pretreatment 89 +/- 17 mmHg; 20 minutes after application of the first dose 67 +/- 17 mmHg; 12 weeks after treatment 74 +/- 14 mmHg (P < 0.005). Recordings of anodermal blood flow showed a significant increase in flow: pretreatment 0.36 +/- 0.25 volts; 20 minutes after application of the first dose 0.59 +/- 0.27; 12 weeks after treatment 0.64 +/- 0.33 (P < 0.005). CONCLUSIONS: Local application of L: -arginine promotes fissure healing without headache as a side effect, and L: -arginine is effective even in patients not responding to isosorbide dinitrate treatment.
Molecular physiology of intestinal n(+)/h(+) exchange.
Zachos NC, Tse M, Donowitz M
Annu Rev Physiol 2005;67:411-43.
The sodium/hydrogen exchange (NHE) gene family plays an integral role in neutral sodium absorption in the mammalian intestine. The NHE gene family is comprised of nine members that are categorized by cellular localization (i.e., plasma membrane or intracellular). In the gastrointestinal (GI) tract of multiple species, there are resident plasma membrane isoforms including NHE1 (basolateral) and NHE2 (apical), recycling isoforms (NHE3), as well as intracellular isoforms (NHE6, 7, 9). NHE3 recycles between the endosomal compartment and the apical plasma membrane and functions in both locations. NHE3 regulation occurs during normal digestive processes and is often inhibited in diarrheal diseases. The C terminus of NHE3 binds multiple regulatory proteins to form large protein complexes that are involved in regulation of NHE3 trafficking to and from the plasma membrane, turnover number, and protein phosphorylation. NHE1 and NHE2 are not regulated by trafficking. NHE1 interacts with multiple regulatory proteins that affect phosphorylation; however, whether NHE1 exists in large multi-protein complexes is unknown. Although intestinal and colonic sodium absorption appear to involve at least NHE2 and NHE3, future studies are necessary to more accurately define their relative contributions to sodium absorption during human digestion and in pathophysiological conditions.
Secretion and absorption by colonic crypts.
Annu Rev Physiol 2005;67:471-90.
The intestines play an important role in the absorption and secretion of nutrients. The colon is the final area for recapturing electrolytes and water prior to excretion, and in order to maintain this electrolyte homeostasis, a complex interaction between secretory and absorptive processes is necessary. Until recently it was thought that secretion and absorption were two distinct processes associated with either crypts or surface cells, respectively. Recently it was demonstrated that both the surface and crypt cells can perform secretory and absorptive functions and that, in fact, these functions can be going on simultaneously. This issue is important in the complexities associated with secretory diarrhea and also in attempting to develop treatment strategies for intestinal disorders. Here, we update the model of colonic secretion and absorption, discuss new issues of transporter activation, and identify some important new receptor pathways that are important modulators of the secretory and absorptive functions of the colon.
The Combination of High Fruit and Vegetable and Low Saturated Fat Intakes Is More Protective against Mortality in Aging Men than Is Either Alone: The Baltimore Longitudinal Study of Aging.
Tucker KL, Hallfrisch J, Qiao N, Muller D, Andres R, Fleg JL
J Nutr 2005 Mar;135(3):556-61.
Saturated fat (SF) intake contributes to the risk of coronary heart disease (CHD) mortality. Recently, the protective effects of fruit and vegetable (FV) intake on both CHD and all-cause mortality were documented. However, individuals consuming more FV may be displacing higher-fat foods. Therefore, we investigated the individual and combined effects of FV and SF consumption on total and CHD mortality among 501 initially healthy men in the Baltimore Longitudinal Study of Aging (BLSA). Over a mean 18 y of follow-up, 7-d diet records were taken at 1-7 visits. Cause of death was ascertained from death certificates, hospital records, and autopsy data. After adjustment for age, total energy intake, BMI, smoking, alcohol use, dietary supplements, and physical activity score, FV and SF intakes were individually associated with lower all-cause and CHD mortality (P < 0.05). When both FV and SF were included in the same model, associations of each were attenuated with CHD mortality, and no longer significant for all-cause mortality. Men consuming the combination of >/=5 servings of FV/d and </=12% energy from SF were 31% less likely to die of any cause (P < 0.05), and 76% less likely to die from CHD (P < 0.001), relative to those consuming <5 FV and >12% SF. Men consuming either low SF or high FV, but not both, did not have a significantly lower risk of total mortality; but did have 64-67% lower risk of CHD mortality (P < 0.05) relative to those doing neither. These results confirm the protective effects of low SF and high FV intake against CHD mortality. In addition, they extend these findings by demonstrating that the combination of both behaviors is more protective than either alone, suggesting that their beneficial effects are mediated by different mechanisms.
Plasticity of the enteric nervous system during intestinal inflammation.
Lomax AE, Fernandez E, Sharkey KA
Neurogastroenterol Motil 2005 Feb;17(1):4-15.
Abstract Inflammation of the bowel causes structural and functional changes to the enteric nervous system (ENS). While morphological alterations to the ENS are evident in some inflammatory conditions, it appears that relatively subtle modifications to the neurophysiology of enteric microcircuits may play a role in gastrointestinal (GI) dysfunction. These include changes to the excitability and synaptic properties of enteric neurones. The response of the ENS to inflammation varies according to the site and type of inflammation, with the functional consequences depending on the nature of the inflammatory stimulus. It has become clear that inflammation at one site can produce changes that occur at remotes sites in the GI tract. Immunohistochemical data from patients with inflammatory bowel disease (IBD) and animal models indicate that inflammation alters the neurochemical content of some functional classes of enteric neurones. A growing body of evidence supports an active role for enteric glia in neuronal and neuroimmune communication in the GI tract, particularly during inflammation. In conclusion, plasticity of the ENS is a feature of intestinal inflammation. Elucidation of the mechanisms whereby inflammation alters enteric neural control of GI functions may lead to novel treatments for IBD.
Relation between anal electrosensitivity and rectal filling sensation and the influence of age.
Broens PM, Penninckx FM
Dis Colon Rectum 2005 Jan;48(1):127-33.
PURPOSE: The aim of this study was to assess the effect of age and sex on the rectal filling sensation and anal electrosensitivity and to explore the relation between anal electrosensitivity and the parameters of the rectal filling sensation. METHODS: Anal mucosal electrosensitivity and anorectal manometry, including the rectal filling sensation test were performed in 19 control subjects; 10 were younger than 60 years and 9 were older than that. Altogether, there were 11 men and 8 women. RESULTS: Anal electrosensitivity did not differ between the two age groups. Women had a significantly lower electrosensitivity 4 and 5 cm from the anal verge than men, as well as a significantly shorter anal high-pressure zone. The rectal filling sensation did not differ between sexes. In the older age group, the rectal volumes required to induce filling sensations were smaller than those observed in the younger age group, but rectal pressures were comparable; as a consequence, rectal compliance was lower in older subjects. Anal electrosensitivity at different anal levels did not correlate with the rectal volume or pressure parameters of successive rectal filling sensations. The pressure recorded in the proximal anal canal at the consecutive rectal filling sensations strongly correlated with the rectal balloon pressure needed to elicit them. CONCLUSIONS: The zones of high anal electrosensitivity and high pressure seem to coincide. The fact that both are shorter in females did not influence the parameters of the rectal filling sensation. Lower rectal volumes but comparable rectal pressures were needed to induce the rectal filling sensation in the older age group. Rectal sensation did not correlate with anal electrosensitivity, probably because the receptors are not stimulated by the type of anal stimulation used or because different receptors are involved. Hence, the rectal filling sensation test cannot be replaced by the simpler anal electrosensitivity test.
Rectal hyposensitivity: a disorder of the rectal wall or the afferent pathway? An assessment using the barostat.
Gladman MA, Dvorkin LS, Lunniss PJ, Williams NS, Scott SM
Am J Gastroenterol 2005 Jan;100(1):106-14.
OBJECTIVES: Rectal hyposensitivity (RH) relates to a diminished perception of rectal distension. Diagnosis on the basis of abnormal threshold volumes on balloon distension alone may be inaccurate due to the influence of differing rectal wall properties. The aim of this study was to investigate whether RH was actually due to impaired afferent nerve function or whether it could be secondary to abnormalities of the rectal wall. METHODS: A total of 50 patients were referred consecutively to a tertiary referral unit for physiologic assessment of constipation (Rome II criteria), 25 of whom had associated fecal incontinence. Thirty patients had RH (elevated threshold volumes on latex balloon distension), and 20 patients had normal rectal sensation (NS). Results were compared with those obtained in 20 healthy volunteers (HV). All subjects underwent standard anorectal physiologic investigation, and assessment of rectal compliance, adaptive response to isobaric distension at urge threshold, and postprandial rectal response, using an electromechanical barostat. RESULTS: Mean rectal compliance was significantly elevated in patients with RH compared to NS and HV (p < 0.001). However, 16 patients with RH (53%) had normal compliance. Intensity of the urge to defecate during random phasic isobaric distensions was significantly reduced in patients with RH compared to NS and HV (p < 0.001). The adaptive response at urge threshold was reduced in patients with RH compared to NS and HV (p < 0.001), although spontaneous adaptation at operating pressure was similar in all three groups studied (p= 0.3). Postprandially, responses were similar between groups. CONCLUSIONS: In patients found to have RH on simple balloon distension, impaired perception of rectal distension may be partly explained in one subgroup by abnormal rectal compliance. However, a second subgroup exists with normal rectal wall properties, suggestive of a true impairment of the afferent pathway. The barostat has an important role in the identification of these subgroups of patients.
Denonvilliers' fascia lies anterior to the fascia propria and rectal dissection plane in total mesorectal excision.
Lindsey I, Warren BF, Mortensen NJ
Dis Colon Rectum 2005 Jan;48(1):37-42.
PURPOSE: Opinion is divided whether Denonvilliers' fascia lies anterior or posterior to the anatomic fascia propria plane of anterior rectal dissection in total mesorectal excision. This study was designed to evaluate this anatomic relationship by assessing the presence or absence of Denonvilliers' fascia on the anterior surface of the extraperitoneal rectum in specimens resected for both nonanterior and anterior rectal cancer in males. METHODS: Surgical specimens were collected prospectively from males undergoing total mesorectal excision for mid and low rectal cancer, with a deep dissection of the anterior extraperitoneal rectum to the pelvic floor. Specimens were histopathologically analyzed using best practice methods for rectal cancer. The anterior aspects of the extraperitoneal rectal sections were examined microscopically for the presence or absence of Denonvilliers' fascia. RESULTS: Thirty rectal specimens were examined. Denonvilliers' fascia was present in 12 (40 percent) and absent in 18 specimens (60 percent). Denonvilliers' fascia was significantly more frequently present when tumor involved (55 percent) rather than spared the anterior rectal quadrant (10 percent; difference between groups 45 percent; 95 percent confidence interval, 30-60 percent; P = 0.024, Fisher's exact test). CONCLUSIONS: When tumors were nonanterior, rectal dissection was conducted on fascia propria in the usual anatomic plane, and Denonvilliers' fascia was not present on the specimen. It was almost exclusively found in anterior tumors, deliberately taken by a radical extra-anatomic anterior dissection in the extramesorectal dissection plane. Denonvilliers' fascia lies anterior to the anatomic fascia propria plane of anterior rectal dissection and is more closely applied to the prostate than the rectum.