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Functional Anatomy: Coloproctology

Gastrointestinal motility: an academic and research perspective.
Quigley EM
Dig Dis. 2006;24(3-4):218-20.

While, in the past, gastrointestinal motility may have been viewed as a narrow and restricted field, confined to the study of twitches in muscle baths and squiggles on smoke drums, it has, of late and belatedly, entered into the mainstream of gastroenterology and medicine. As a consequence, this field, now more correctly and appropriately described as neurogastroenterology, concerns itself with a vast spectrum of clinical disorders of varying pathophysiology, presentation and management. Never before has this area offered so many opportunities to the budding academician and researcher.


Electrical activity in the rectum of anaesthetized dogs.
Lammers WJ, Abazer FA, Ver Donck L, Smets D, Schuurkes JA, Coulie B
Neurogastroenterol Motil. 2006 Jul;18(7):569-77.

There is limited data available on the electrical activity of the rectum. An in vivo canine model was developed to record 240 extracellular electrograms simultaneously from the serosal surface of the rectum thereby enabling an off-line reconstruction of the behaviour of the electrical signals. Serosal rectal electrical activity is characterized by brief bursts of action potentials (=spikes) with a frequency of 22 cycles min(-1). High-resolution mapping of these signals revealed predominant propagation of these spikes in the longitudinal direction, originating from any site and conducted for a limited time and length before stopping spontaneously, thereby describing a patch of activity. The dimension of the patches in the longitudinal direction was significantly longer than the transversal width (13.6 vs 2.4 mm; P < 0.001). Spike propagation could occur in the aboral (46% of cases), in the oral (34%) or in both directions (20%). A bolus of betanechol (i.v., 0.5 mg kg(-1)) increased the frequency of the spikes without affecting size, shape or orientation of the patches. As in other parts of the gastrointestinal system, individual spike propagation in the rectum is limited to small areas or patches. The contractile activity of the organ could possibly reflect this underlying pattern of electrical behaviour.

Intramuscular interstitial cells of Cajal associated with mast cells survive nitrergic nerves in achalasia.
Zarate N, Wang XY, Tougas G, Anvari M, Birch D, Mearin F, Malagelada JR, Huizinga JD
Neurogastroenterol Motil. 2006 Jul;18(7):556-68.

Achalasia is dominated by injury to inhibitory nerves. As intramuscular interstitial cells of Cajal (ICC-IM) are proposed to form functional units with nitrergic nerves, their fate in achalasia may be critically important. We studied the relationship between loss of nitrergic nerves and injury to ICC-IM in patients with achalasia and determined associations between ICC-IM and mast cells (MC), using quantitative immunohistochemistry and electron microscopy. Loss of neuronal nitric oxide synthase (nNOS) immunoreactivity was completed within 3 years of acquiring achalasia. Thereafter, progressive ultrastructural injury to remaining nerve structures was evident. Within the first 2 years, the number of ICC-IM did not decline although ultrastructural injury was already present. Thereafter, loss of ICC-IM occurred unrelated to duration of disease. Damage to ICC-IM appeared unrelated to nerve injury. A significant MC infiltration was observed in the musculature; the number of MC was positively related to the persistent number of ICC-IM. Mast cell formed close contacts with ICC-IM and piecemeal-degranulation occurred towards ICC-IM. In conclusion, injury to ICC-IM in achalasia is variable, but not related to duration of disease and injury to nitrergic nerves. MC are prominent and form close functional contact with ICC-IM which may be responsible for their relatively long survival.

The emerging role of PDZ adapter proteins for regulation of intestinal ion transport.
Lamprecht G, Seidler UE
Am J Physiol Gastrointest Liver Physiol. 2006 Jun 22;.

In the gastrointestinal tract CFTR, in conjunction with one or several members of the SLC26 an-ion exchanger family, mediates electrogenic Cl(-) and HCO3(-) secretion. NHE3, on the other hand, coupled to one or several of the SLC26 isoforms, mediates electroneutral NaCl absorption. The agonist-induced activation of anion secretion and inhibition of salt absorption causes secretory diarrhea. Current dogma sees the formation of a multiprotein complex of transport proteins, PDZ adapter proteins, anchoring proteins, the cytoskeleton, and the involved protein kinases as one crucial step in the regulation of these transport processes. Data obtained in heterologous expression studies suggest an important role of these PDZ adapter proteins in trafficking, endocytic recycling, and membrane retention of the respective transmembrane proteins. This article reviews recent advances in our understanding of the role of the PDZ adapter proteins NHERF, E3KARP, PDZK1, IKEPP (NHERF-1 to NHERF-4), CAL and Shank-2 that bind to CFTR, NHE3 and the intestinal SLC26 members, in the regulation of intestinal fluid transport. Current concepts are mostly derived from heterologous expression studies, and studies on their role in organ physiology are still in infancy. Recently, however, PDZ adapter protein deficient mice and organ-specific cell lines have become available, and the first results suggest a more cell-type and possibly signal-specific role of these adapter proteins. This opens the potential for drug development targeted to PDZ domain interactions, which is in theory one of the most efficient anti-diarrheal strategies.


Neurophysiological evaluation of healthy human anorectal sensation

Harris ML, Hobson AR, Hamdy S, Thompson DG, Akkermans LM, Aziz Q
Am J Physiol Gastrointest Liver Physiol. 2006 May 11;.

Patients with functional gastrointestinal disorders often demonstrate abnormal visceral sensation. Currently, rectal sensation is assessed by manual balloon distension or barostat. However, neither test is adaptable for use in neurophysiological characterisation of visceral afferent pathways by sensory evoked potentials. The aim of this study was to assess reproducibility and quality of sensation evoked by electrical stimulation (ES) and rapid balloon distension (RBD) in anorectum and to apply the optimum stimulus to examine the visceral afferent pathway with rectal evoked potentials (REP). Healthy subjects (n=8, median age 33 years) were studied on three separate occasions. Variability, tolerance and stimulus characteristics were assessed with each technique. Overall ES consistently invoked pain and was chosen for measuring REP whereas RBD in all cases induced the strong urge to defecate. Rectal intra-class correlation coefficient (ICC) for ES and RBD (0.82 and 0.72 respectively) demonstrated good reproducibility at pain/maximum tolerated volume but not sensory threshold. Only sphincter ICC for ES at pain showed acceptable between study reproducibility (ICC 0.79). Within studies ICC was good (>0.6) for anorectal ES and RBD at both levels of sensation. All subjects reported significantly more unpleasantness during RBD than ES (P<0.01). This study demonstrates that ES and RBD are similarly reproducible. However, the sensations experienced with each technique differed markedly, probably reflecting differences in peripheral and/or central processing of the sensory input. This is of relevance in interpreting findings of neuroimaging studies of anorectal sensation and may provide insight into physiological characteristics of visceral afferent pathways in health and disease.

Cerebral representation of the anorectum using functional magnetic resonance imaging.
Bittorf B, Ringler R, Forster C, Hohenberger W, Matzel KE
Br J Surg. 2006 Jun 6;.

BACKGROUND:: Anorectal continence depends not only on the organs of continence but also on cerebral control. There are relatively few data regarding cerebral processing of anorectal continence. METHODS:: Thirteen healthy subjects underwent rectal distension to cause urge increasing to discomfort during functional magnetic resonance imaging (fMRI). In addition, a painful heat stimulus was applied to the skin of the anterior abdominal wall in the dermatome corresponding to the rectum. Voluntary contraction of the anal sphincter was also performed. Subjective rating of stimulus intensity was recorded. Evaluation of the data used a general linear model with Brain Voyager(trade mark). RESULTS:: Subjective sensation of discomfort increased during repeated rectal distension and caused activation in the anterior cingulate gyrus, insula, thalamus and secondary somatosensory cortex seen on fMRI. Perception of rectal urge and discomfort activated the same cerebral regions with differing intensity. Application of a painful thermal stimulus in the corresponding dermatome showed a modification of the response. Voluntary contraction of the anal sphincter led to activation of the motor cortex and increased activity in the supplementary motor cortex and the insula. CONCLUSION:: Cerebral representation of the anorectum as mapped by fMRI is intricate and reflects the complexity of the continence mechanism. Copyright (c) 2006 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

Drugs affecting visceral sensitivity: ready for the prime time?
Delvaux MM, Gay G
Dig Dis. 2006;24(1-2):99-104.

Visceral sensitivity has been recognized over the last decade as a frequent pathophysiological component of functional bowel disorders. Studies in animals and humans have identified numerous neurotransmitters involved in the processing of sensations from the gut to the brain. However, up to now none of them has actually been proven to have a marked clinical efficacy and the benefit comes rather from their action of bowel disturbances. Reproducible tests are lacking to detect visceral hypersensitivity in humans and distension tests are difficult to undertake in a clinical setting. Therefore, abnormal visceral sensitivity may not be regarded as a tool to select IBS patients as candidates for a given treatment.

Peripheral opioids for functional GI disease: a reappraisal.
Lembo A
Dig Dis. 2006;24(1-2):91-8.

Opioids have been used medicinally and recreationally for thousands of years. The clinical use of opioids for gastrointestinal conditions has been limited by central nervous system side effects. A new generation of peripheral opioid receptor ligands free of central nervous system side effects is being developed. Clinical trials with the peripherally acting mu opioid receptor antagonists' alvimopan and N-methylnaltrexone show promise for improving postoperative ileus- and opioid-induced constipation. Likewise, preliminary studies with the peripherally acting kappa opioid agonist fedotozine showed promise in the treatment of irritable bowel syndrome (IBS) and functional dyspepsia. Further studies are on hold presumably due to lack of efficacy in subsequent studies. However, clinical studies are underway for newer kappa opioid agonists such as asimadoline and ADL 10-0101.

Tachykinin receptors as drug targets for motility disorders.
Hoogerwerf WA, Sarna SK
Dig Dis. 2006;24(1-2):83-90.

The tachykinins and their receptors are strategically distributed within the gut wall, spinal cord, and central nervous system to be potential targets of therapeutic agents for gastrointestinal motility disorders. However, the development of effective tachykinin receptor agonists or antagonists to treat these disorders has had very limited success so far. This is, in part, due to the complex and multilevel of regulation of gastrointestinal motility function and the challenges faced in targeting the specific type of gut contraction to normalize function in disease state.

CCK1 antagonists: are they ready for clinical use?
Peter SA, D'Amato M, Beglinger C
Dig Dis. 2006;24(1-2):70-82.

Cholecystokinin (CCK) is a peptide hormone which is found both in the gastrointestinal tract throughout the human small intestine and nerves in the myenteric plexus of the enteric nervous system and in the central nervous system. This dual location constitutes the anatomical basis for this in functions as a hormone and a neurotransmitter implicated in the regulation of both systems. CCK regulates not only motor functions in the gastrointestinal tract like lower oesophageal sphincter relaxation, gastric secretion and emptying, gall bladder contractility and bile secretion into the duodenum, intestinal and colonic motility, but also sensory functions and plays a role in the regulation of food intake. These effects are mediated through selective receptors CCK1 and CCK2. Over the last few years, research has focused on understanding the role of CCK, its receptors with antagonists at the biological, pharmacological, clinical and therapeutic level. As far as the CCK1 antagonists is concerned, important inroads have been made in the potential role of these antagonists in the treatment of GERD, IBS and pancreatitis. They have also shown encouraging results in sphincter of Oddi dysfunction and some gastrointestinal cancers. This review focuses on the recent ad vances of the biological role of CCK and their CCK1 antagonists: their current basic and clinical status in gastroenterology, with particular emphasis on the potential therapeutic role of the CCK1 antagonists and future research directions.

Drugs acting on serotonin receptors for the treatment of functional GI disorders.
Tonini M, Pace F
Dig Dis. 2006;24(1-2):59-69.

In the gut, serotonin (5-hydroxytryptamine: 5-HT) exerts a variety of effects on intrinsic enteric neurons, extrinsic afferents, enterocytes and smooth muscle cells, which are related to the expression of multiple 5-HT receptor types and subtypes regulating motility, vascular tone, secretion and perception. Agonists and antagonists at 5-HT receptors have gained access to the market for the two major variants of the irritable bowel syndrome (IBS), a functional disorder characterized by abdominal pain associated with diarrhea and/or constipation in the absence of any organic abnormality. Indeed, the 5-HT3 receptor antagonist alosetron is available in the US market for the treatment of women with severe, diarrhea-predominant IBS (D-IBS) refractory to conventional therapy, whereas tegaserod, a partial 5-HT4 receptor agonist, has been approved by the FDA and other regulatory agencies for the treatment of women with constipation-predominant IBS (C-IBS) or functional constipation. This review is mainly intended to discuss the role of non-neuronal (paracrine) and neuronal 5-HT in the pathophysiology of functional gastrointestinal disorders (FGIDs), such as IBS and functional dyspepsia, and the mechanisms through which drugs acting on 5-HT receptors regulate visceral motility, perception and secretion in these two conditions.

Role of the Jejunum Versus Ileum on Intestinal Gas Dynamics During a Balanced Meal in Healthy Subjects.
Harder H, Hernando-Harder AC, Franke A, Krammer HJ, Singer MV
Dig Dis Sci. 2006 Jun 7;.

Under physiological conditions, the human gut adapts intestinal gas propulsion and evacuation to prevent intestinal gaseous complaints In this study we aimed to determine influences of the jejunum versus ileum on intestinal gas dynamics during a balanced meal. Paired studies were randomly performed with seven women and three men, ages 28-42. A mixed liquid meal was infused (1 kcal/min) into the duodenum. After 30 min, gas was infused (12 ml/min) into the jejunum or ileum for 150 min. Gas expulsion was measured, and perception and girth changes were assessed. Postprandial intestinal gas propulsion was uneventful and recovery complete, with -7+/- 58 and -92+/- 44 ml final intestinal gas retention for jejunal and ileal gas infusion, respectively. Neither significant differences in abdominal perception nor changes in abdominal girth were seen. During a balanced meal, intestinal gas is effectively propulsed aborally, and this does not depend on the site of the small intestinal stimulation.

Inhibitory Effects and Mechanisms of Colonic Electric Stimulation on Gastric and Rectal Tone in Conscious Dogs.
Liu S, Lei Y, Chen JD
Dis Colon Rectum. 2006 Jun 8;.

PURPOSE: Colonic electric stimulation has been shown to alter motor functions of the colon; however, its effects on other organs of the gut have been investigated rarely. METHODS: This study was performed in 12 dogs implanted with one pair of colonic serosal electrodes and a gastric cannula. Experiments were performed to study: 1) the effect of colonic electric stimulation on proximal gastric tone and compliance; 2) the effect of colonic electric stimulation on rectal tone and compliance; 3) the sympathetic mechanism involved in the effects of colonic electric stimulation on gastric/rectal tone. A computerized barostat was used to assess gastric/rectal tone and compliance. RESULTS: Colonic electric stimulation inhibited both gastric and rectal tone with a higher potency in gastric tone. Colonic electric stimulation reduced gastric but not rectal compliance. The inhibitory effect of colonic electric stimulation on gastric tone but not rectal tone was abolished by an adrenergic blockade, guanethidine. CONCLUSIONS: Colonic electric stimulation inhibits both gastric and rectal tone with a higher potency in inhibiting gastric tone. Colonic electric stimulation reduces gastric but not rectal compliance. The inhibitory effect of colonic electric stimulation on gastric tone seems to be mediated by the sympathetic pathway.

Molecular characterization and distribution of motilin family receptors in the human gastrointestinal tract.
Takeshita E, Matsuura B, Dong M, Miller LJ, Matsui H, Onji M
J Gastroenterol. 2006 Mar;41(3):223-30.

BACKGROUND: Motilin and ghrelin have been recognized as important endogenous regulators of gastrointestinal motor function in mammals, mediated respectively by the motilin receptor and by the closely related ghrelin receptor. The aims of this study were to explore the distribution of motilin and ghrelin receptors along the human gastrointestinal tract and to establish the molecular nature of the human motilin receptor. METHODS: Post mortem and surgical human tissue specimens with no hemorrhage, necrosis, or tumor were obtained from various parts of the gastrointestinal tract. We analyzed levels of expression of mRNA for motilin and ghrelin receptors and examined their molecular identities. Portions of some specimens were also studied by immunohistochemistry for expression of the motilin and ghrelin receptor. RESULTS: The long form of the motilin receptor, but not the short form, was expressed in all parts of the gastrointestinal tract, and expressed at higher levels in muscle than in mucosa. Motilin receptor immunoreactivity was present in muscle cells and the myenteric plexus, but not in mucosal or submucosal cells. In contrast, ghrelin receptor mRNA was expressed equally in all parts of the gastrointestinal tract, with similar levels of expression in mucosal and muscle layers. CONCLUSIONS: Both the motilin and ghrelin receptors are expressed along the human gastrointestinal tract, but they have clearly distinct distributions in regard to both level and layer. The diffuse muscle expression of the motilin receptor, at both the levels of the gene and the protein product, along the entire gastrointestinal tract makes it a useful potential target for motilide drugs for dysmotility.

Differential modulation in the functions of intestinal dendritic cells by long- and medium-chain fatty acids.
Tsuzuki Y, Miyazaki J, Matsuzaki K, Okada Y, Hokari R, Kawaguchi A, Nagao S, Itoh K, Miura S
J Gastroenterol. 2006 Mar;41(3):209-16.

BACKGROUND: Although dendritic cells (DCs) play significant roles in intestinal immune responses, little is known regarding the direct effects of luminal foods on DC functions in the intestinal mucosa. In this study, we examined the effects of fatty acids (FAs) with various chain length on the phagocytic function, antigen presentation, and chemotaxis of intestinal DCs. METHODS: DCs obtained from the thoracic duct lymph of mesenteric lymphadenectomized rats were cultured with long [arachidonic acid (AA) or oleic acid] or medium (octanoic acid) chain FAs with interleukin-4 and granulocyte macrophage-colony stimulating factor. Tumor necrosis factor-alpha was added in the maturation group. Phagocytic function was examined by the intake of fluorescent microbeads. The expression of cell surface molecules was determined by immunocytochemistry or fluorescence-activated cell sorting (FACS). Antigen presentation ability was evaluated by coincubating keyhole limpet hemocyanin (KLH)-sensitized spleen lymphocytes and KLH-pulsed DCs. Migratory ability of DCs toward the chemokines CC chemokine ligand (CCL) 20 and CCL21 was also assessed. RESULTS: There was a maturation-induced decrease in phagocytic function, and an increased expression of major histocompatibility complex (MHC) class II molecules. Exposure of DCs to both long- and medium-chain FAs maintained phagocytic ability. The expression of MHC class II molecules was significantly suppressed only by long-chain FAs. The expression of costimulatory factors was suppressed only by AA. Long- but not medium-chain FAs suppressed the antigen presentation ability of DCs induced by maturation. Chemotactic ability of mature DCs toward CCL21 was abrogated only by long-chain FAs. CONCLUSIONS: The data suggest that intraluminal exposure to long- and medium-chain FAs may differentially modulate the immune functions of intestinal DCs.


Colonic health: fermentation and short chain fatty acids.
Wong JM, de Souza R, Kendall CW, Emam A, Jenkins DJ
J Clin Gastroenterol. 2006 Mar;40(3):235-43.

Interest has been recently rekindled in short chain fatty acids (SCFAs) with the emergence of prebiotics and probiotics aimed at improving colonic and systemic health. Dietary carbohydrates, specifically resistant starches and dietary fiber, are substrates for fermentation that produce SCFAs, primarily acetate, propionate, and butyrate, as end products. The rate and amount of SCFA production depends on the species and amounts of microflora present in the colon, the substrate source and gut transit time. SCFAs are readily absorbed. Butyrate is the major energy source for colonocytes. Propionate is largely taken up by the liver. Acetate enters the peripheral circulation to be metabolized by peripheral tissues. Specific SCFA may reduce the risk of developing gastrointestinal disorders, cancer, and cardiovascular disease. Acetate is the principal SCFA in the colon, and after absorption it has been shown to increase cholesterol synthesis. However, propionate, a gluconeogenerator, has been shown to inhibit cholesterol synthesis. Therefore, substrates that can decrease the acetate: propionate ratio may reduce serum lipids and possibly cardiovascular disease risk. Butyrate has been studied for its role in nourishing the colonic mucosa and in the prevention of cancer of the colon, by promoting cell differentiation, cell-cycle arrest and apoptosis of transformed colonocytes; inhibiting the enzyme histone deacetylase and decreasing the transformation of primary to secondary bile acids as a result of colonic acidification. Therefore, a greater increase in SCFA production and potentially a greater delivery of SCFA, specifically butyrate, to the distal colon may result in a protective effect. Butyrate irrigation (enema) has also been suggested in the treatment of colitis. More human studies are now needed, especially, given the diverse nature of carbohydrate substrates and the SCFA patterns resulting from their fermentation. Short-term and long-term human studies are particularly required on SCFAs in relation to markers of cancer risk. These studies will be key to the success of dietary recommendations to maximize colonic disease prevention.

Probiotics for women's health.
Onderdonk AB
J Clin Gastroenterol. 2006 Mar;40(3):256-9.

GOALS: The goals of this research were 2-fold: (1) to determine whether a commercially available probiotic mixture (VSL-3) could survive and grow in a continuous culture system simulating the vaginal environment and (2) to determine whether the probiotic mixture was capable of suppressing the growth of a known vaginal vault pathogen, Gardnerella vaginalis. BACKGROUND: An abnormal vaginal microflora, such as that associated with bacterial vaginosis (BV) is an important health issue for women. In addition, the association of this condition with preterm labor and delivery suggests that control of BV may impact the number of preterm births. Interventional trials with antibiotics have received mixed reviews and other interventional options, including the use of probiotics, are being considered. STUDY: A well-documented continuous culture system has been used to determine whether VSL-3 can survive and grow in conditions simulating a vaginal environment. In addition, the ability of VSL-3 to inhibit the growth of a known vaginal vault pathogen, G. vaginalis, has been determined. RESULTS: The probiotic mixture was shown to survive and maintain itself within the fermentation vessel of the continuous culture system over an extended period of time. This mixture, when challenged with a known pathogen, was also shown to suppress the growth of G. vaginalis. CONCLUSIONS: It may be feasible to use probiotics as interventional therapy to suppress the growth of pathogens within the vaginal vault associated with BV.

Probiotics and the immune response.
Madsen K
J Clin Gastroenterol. 2006 Mar;40(3):232-4.

Beneficial effects exerted by probiotic bacteria in the treatment of human disease may be broadly classified as those effects which arise due to activity in the large intestine and are related to colonization or inhibition of pathogen growth; and those effects which arise in both the small and large intestine, and are related to enhancement of the host immune response and intestinal barrier function. In a strain dependent fashion, probiotic bacteria can enhance intestinal barrier function and modulate signal transduction pathways and gene expression in epithelial and immune cells. Oral administration of live probiotics and bacterial structural components can also differentially modulate dendritic cells resulting in an increased production of IL-10 and regulatory T cells. Both innate and adaptive immune responses can be modulated by probiotic bacteria.

Interindividual differences in microbial counts and biochemical-associated variables in the feces of healthy Spanish adults.
Delgado S, Ruas-Madiedo P, Suarez A, Mayo B
Dig Dis Sci. 2006 Apr;51(4):737-43.

The aim of this study was to examine, over a period of 1 year, interindividual variations in the most prominent and representative of the cultivatable microbial populations in the feces of eight healthy Spanish persons. A number of biochemical variables (enzyme activities and ammonium and short-chain fatty acid [SCFA] concentrations) thought to be influenced by the GIT microbiota were also analyzed. Total cultivatable microbial counts ranged from 10(10) to 10(11) cfu/g of feces. The largest populations were obligate anaerobes belonging to the Clostridium clusters, followed by species of bifidobacteria and bacteroides. Coliforms and lactobacilli were found at a more intermediate level (10(5)-10(9) cfu/g). The predominant anaerobe populations remained quite constant over time, but all other microbial groups showed significant interindividual differences. Enzyme profiles were individual-dependent, but within subjects, moderate to high intersample variations over time were recorded for some activities. Fecal ammonium concentration was the most unpredictable variable; this fluctuated widely between individuals and samples. Acetic acid was the most abundant SCFA in the feces, followed by butyric and propionic acids. SCFA concentrations also varied according to the individual; some subjects showed specific profiles in terms of SCFA composition or concentration. The fecal microbial and biochemical parameters studied seemed to be individual-dependent. Most variables were rather stable over time, while others (e.g., ammonium concentration) varied widely.

Colonic electrical stimulation regulates colonic transit via the nitrergic pathway in rats.
Liu S, Chen JD
Dig Dis Sci. 2006 Mar;51(3):502-5.

Gastrointestinal electrical stimulation has been proposed for the treatment of gastrointestinal motor disorders. However, little is known about potential roles of colonic electrical stimulation (CES). The aim of this study was to evaluate the effect and mechanism of CES on colonic transit in conscious rats. Male rats (N = 14) were equipped with a pair of colonic serosal electrodes for stimulation and a catheter in the colon. Colonic transit was assessed in four randomized sessions with or without CES and with or without nitric oxide synthesis blocker, L-NNA, by calculating the output of phenol red from the anus every 10 min for 90 min. Results were as follows. (1) CES with trains of short pulses significantly enhanced colonic transit. Colonic emptying was 57.3 +/- 6.1% in the control session and 81.9 +/- 4.6% with CES at 90 min, reflecting a 43% increase. (2) L-NNA delayed colonic transit compared with saline and prevented the accelerative effect of CES on colonic transit. We conclude that CES has an excitatory effect on colonic transit and this excitatory effect may be mediated via the nitrergic pathway.

Applied principles of neurogastroenterology: physiology/motility sensation.
Kellow JE, Azpiroz F, Delvaux M, Gebhart GF, Mertz HR, Quigley EM, Smout AJ
Gastroenterology. 2006 May;130(5):1412-20.

Many of the symptoms prominent in the functional gastrointestinal disorders (FGIDs) are consistent with dysfunction of the sensory and/or motor apparatus of the digestive tract. Assessment of these phenomena in man can be undertaken by using a wide variety of invasive and noninvasive techniques, some well established and others requiring further validation. By using such techniques, alterations in both sensory and motor function have been reported in the FGIDs; various combinations of such dysfunction occur in different regions of the digestive tract in the FGIDs. Our understanding of the origins of this gut sensorimotor dysfunction is gradually increasing. Thus, inflammatory, immunologic, and other processes, as well as psychosocial factors such as stress, can alter the normal patterns of sensitivity and motility through alterations in local reflex activity or via altered neural processing along the brain-gut axis. In this context, a potential role of genetic factors, early-life influences, enteric flora, dietary components, and autonomic dysfunction also should be considered in the disease model. A firm relationship between sensorimotor dysfunction and the production of symptoms, however, has been difficult to show, and so the clinical relevance of the former requires continuing exploration. Based on the conceptual framework established to date, a number of recommendations for further progress can be made.

Fundamentals of neurogastroenterology: basic science.
Grundy D, Al-Chaer ED, Aziz Q, Collins SM, Ke M, Tache Y, Wood JD
Gastroenterology. 2006 May;130(5):1391-411.

The focus of neurogastroenterology in Rome II was the enteric nervous system (ENS). To avoid duplication with Rome II, only advances in ENS neurobiology after Rome II are reviewed together with stronger emphasis on interactions of the brain, spinal cord, and the gut in terms of relevance for abdominal pain and disordered gastrointestinal function. A committee with expertise in selective aspects of neurogastroenterology was invited to evaluate the literature and provide a consensus overview of the Fundamentals of Neurogastroenterology textbook as they relate to functional gastrointestinal disorders (FGIDs). This review is an abbreviated version of a fuller account that appears in the forthcoming book, Rome III. This report reviews current basic science understanding of visceral sensation and its modulation by inflammation and stress and advances in the neurophysiology of the ENS. Many of the concepts are derived from animal studies in which the physiologic mechanisms underlying visceral sensitivity and neural control of motility, secretion, and blood flow are examined. Impact of inflammation and stress in experimental models relative to FGIDs is reviewed as is human brain imaging, which provides a means for translating basic science to understanding FGID symptoms. Investigative evidence and emerging concepts implicate dysfunction in the nervous system as a significant factor underlying patient symptoms in FGIDs. Continued focus on neurogastroenterologic factors that underlie the development of symptoms will lead to mechanistic understanding that is expected to directly benefit the large contingent of patients and care-givers who deal with FGIDs.

Decrease in rat internal anal pressure with the use of a topical ointment containing a killed E. coli culture suspension.
Kido H, Yasukawa H, Hirota T, Shindo A, Naruse T
Int J Colorectal Dis. 2006 Apr 21;.

OBJECTIVES: The present study aimed to clarify the mechanisms of a topical ointment containing an Escherichia coli culture suspension and hydrocortisone (Posterisan forte, BCS+HC) in lowering internal anal pressure in conscious rats. MATERIALS AND METHODS: Internal anal pressure was measured using a water-filled balloon system for consecutive 10-min periods. The changes in pressure were evaluated by the number of peaks above 20 mmH(2)O between 1 and 8 min of recording. RESULTS: Topical intra-anal application of BCS+HC ointment (160 mg/kg) significantly decreased the internal anal pressure at 3 h after the application. Thereafter, this effect reached a maximum decrease at 4 h and lasted until 6 h. BCS+HC ointment (40, 80, and 160 mg/kg) lowered the internal anal pressure at 4-5 h in a dose-dependent manner. The maximum decrease ratios of the ointment and corresponding hydrocortisone-free ointment (Posterisan, BCS) were 32.6+/-12.7 and 25.7+/-9.0%, respectively, revealing significant pressure-lowering effects compared with a placebo (P<0.05). In contrast, the same ointment containing hydrocortisone alone and other ointments containing steroids or local anesthetics had no effects. DISCUSSION: Treatment with 1 mg/kg N(G)-nitro-L: -arginine methyl ester HCl (L: -NAME), a non-selective nitric oxide synthase inhibitor, significantly suppressed the effect of BCS+HC ointment (160 mg/kg) in lowering the internal anal pressure. Furthermore, BCS+HC ointment (160 mg/kg) significantly lowered capsaicin-induced high internal anal pressure compared to a placebo. CONCLUSION: These findings suggest that BCS+HC and BCS ointments containing an E. coli culture suspension significantly lowered the internal anal pressure due to endogenous nitric oxide production in conscious rats.

Magnetic resonance imaging of the levator ani in the squirrel monkey: a comparison of muscle volume between a cohort with pelvic organ prolapse and matched normals.
Kramer LA, Gendron JM, Pierce LM, Runge VM, Shull BL, Kuehl TJ
Am J Obstet Gynecol. 2006 May;194(5):1467-71.

OBJECTIVE: Magnetic resonance imaging was used to test whether squirrel monkeys with pelvic organ prolapse have reduced pelvic muscle volumes, compared with matched normals. STUDY DESIGN: Levator ani and obturator internus volumes obtained from T1-weighted axial scans of matched groups were measured. Muscle volumes and weights were compared for animals necropsied after magnetic resonance imaging. RESULTS: Two observers concurred on measures of levator ani and obturator internus (Kendal tau > or = 0.60 with P < .003). Levator ani volume was related to mass (R2 = 0.62, P = .0009). Animals with pelvic organ prolapse did not differ (P = .67, Wilks multivariate test) from those without pelvic organ prolapse in age, parity, and weight. Levator ani differed between groups (pelvic organ prolapse = 520 mm3 versus normals = 392 mm3, P = .015) and not sides (P = .80). The obturator internus did not differ between groups (P = .29) or sides (P = .72). CONCLUSION: Magnetic resonance imaging demonstrates that levator ani volumes in parous squirrel monkeys with pelvic organ prolapse were not reduced, suggesting that prolapse is not related to pelvic muscle size reduction in this species.

Distribution and immunohistochemical characterization of primary afferent neurons innervating the levator ani muscle of the female squirrel monkey.
Pierce LM, Rankin MR, Foster RT, Dolber PC, Coates KW, Kuehl TJ, Thor KB
Am J Obstet Gynecol. 2006 Apr 22;.

OBJECTIVE: This study was undertaken to examine the neurofilament and neurochemical composition of subpopulations of primary afferent neurons innervating the levator ani muscle by combining retrograde tracing and triple labeling immunofluorescence in the female squirrel monkey. STUDY DESIGN: Cholera toxin B subunit (CTB) was injected unilaterally into the levator ani muscle of 3 monkeys to identify primary sensory neurons in the dorsal root ganglia (DRG) and their central projections in the spinal cord. L7-S2 DRG were processed for dual or triple labeling immunofluorescence 3 days after injection to examine labeling of the 200 kD neurofilament marker RT97 (a marker of myelinated neurons), calcitonin gene-related peptide (CGRP; a marker of peptidergic neurons), isolectin B4 (IB4; a marker of small, unmyelinated neurons), and nerve growth factor receptor (TrkA) in CTB-positive neurons. RESULTS: RT97-negative (C-fiber) neurons were more numerous (74% of total CTB-labeled neurons) and smaller in size than RT97-positive (A-fiber) afferent neurons (26% of CTB-labeled neurons). IB4 labeling was almost exclusively found in RT97-negative afferent neurons. Approximately 43% of all CTB-labeled DRG neurons expressed CGRP, and the majority of these were small. The distribution and sizes of CTB-labeled TrkA-positive DRG neurons were similar to those of CTB-labeled CGRP-positive DRG neurons. CONCLUSION: The levator ani muscle is innervated by 3 major subpopulations of primary afferent neurons consisting of cells with large, neurofilament-rich soma and A fibers (putative proprioceptive neurons) and those with small, peptidergic or nonpeptidergic, neurofilament-poor soma and C fibers (putative nociceptive, mechanoreceptive, ergoreceptive, and thermoreceptive neurons). Future investigation is needed to elucidate the relationship between primary sensory neuron subpopulations and changes in neuropeptide and neurotrophin expression on experimental levator ani nerve damage, childbirth, and aging.

External anal sphincter volume measurements using 3-dimensional endoanal ultrasound.
Gregory WT, Boyles SH, Simmons K, Corcoran A, Clark AL
Am J Obstet Gynecol. 2006 May;194(5):1243-8. Epub 2006 Apr 21.

OBJECTIVE: Significant nerve injury to a muscle can be associated with muscle atrophy and volume loss. Three-dimensional (3D) ultrasound can measure muscle volume, but the reproducibility of the technique has not been established for the anal sphincter. STUDY DESIGN: Using a 10 MHz 360-degree rotating endoanal probe, we performed 3D endoanal ultrasounds on 9 nulliparous and 23 asymptomatic primiparous subjects at 12 weeks' postpartum. Two blinded examiners measured the length of the external anal sphincter (EAS) from a midsagittal image, and the width of the EAS and internal anal sphincter (IAS) from axial images at mid anal canal. The EAS volume was calculated by repetitively outlining only the EAS in each sequential axial view. Both examiners measured the EAS volumes twice, blinded to previous calculations. RESULTS: The intrarater reliability for EAS volume was 0.79 to 0.89 (intraclass coefficient). The mean difference of the EAS volume between the 2 examiners was 0.5 mL (P = .3, t test). Correlation between the 2 examiners for measuring EAS volume was r = 0.77 (P < .001, Pearson's). The "limits of agreement" (between 2 examiners) varied by as much as 40% of the mean volume. CONCLUSION: Quantitative 3D ultrasound of the anal sphincter is moderately reproducible.

The cell adhesion molecule l1 is required for chain migration of neural crest cells in the developing mouse gut.
Anderson RB, Turner KN, Nikonenko AG, Hemperly J, Schachner M, Young HM
Gastroenterology. 2006 Apr;130(4):1221-32.

BACKGROUND & AIMS: During development, the enteric nervous system is derived from neural crest cells that emigrate from the hindbrain, enter the foregut, and colonize the gut. Defects in neural crest migration can result in intestinal aganglionosis. Hirschsprung's disease (congenital aganglionosis) is a human condition in which enteric neurons are absent from the distal bowel. A number of clinical studies have implicated the cell adhesion molecule L1 in Hirschsprung's disease. We examined the role of L1 in the migration of neural crest cells through the developing mouse gut. METHODS: A variety of in vitro and in vivo assays were used to examine: (1) the effect of L1 blocking antibodies or exogenous soluble L1 protein known to compromise L1 function on the rate of crest cell migration, (2) the effect of blocking L1 activity on the dynamic behavior of crest cells using time-lapse microscopy, and (3) whether the colonization of the gut by crest cells in L1-deficient mice differs from control mice. RESULTS: We show that L1 is expressed by neural crest cells as they colonize the gut. Perturbation studies show that disrupting L1 activity retards neural crest migration and increases the number of solitary neural crest cells. L1-deficient mice show a small but significant reduction in neural crest cell migration at early developmental stages, but the entire gastrointestinal tract is colonized. CONCLUSIONS: L1 is important for the migration of neural crest cells through the developing gut and is likely to be involved in the etiology of Hirschsprung's disease.

Dietary Fiber Enhances a Tumor Suppressor Signaling Pathway in the Gut.
Nguyen KA, Cao Y, Chen JR, Townsend CM Jr, Ko TC
Ann Surg. 2006 May;243(5):619-627.

OBJECTIVE:: To determine whether sodium butyrate (NaB), a major short-chain fatty acid produced in the human gut by bacterial fermentation of dietary fiber, enhances transforming growth factor (TGF)-beta signaling and potentiates its tumor suppressor activity in the gut. SUMMARY BACKGROUND DATA:: The molecular mechanisms by which dietary fiber decreases the risk of colon cancers are poorly characterized. TGF-beta is an important tumor suppressor in the gut and has many similar biologic activities as NaB. Therefore, we hypothesized that the chemo-preventive effects of NaB are mediated in part by enhancing TGF-beta signaling and its tumor suppressor function in the gut. METHODS:: The effects of NaB on Smad3 expression in rat intestinal epithelial (RIE-1) cells and 6 human colon cancer cell lines were examined. The effects of NaB on TGF-beta-induced Smad3 phosphorylation and plasminogen activator inhibitor-1 (PAI-1) and cyclooxygenase-2 (COX-2) gene expression were also examined in RIE-1 cells. Finally, the effects of NaB and TGF-beta on anchorage-independent growth were examined in Akt-transformed RIE-1 cells. RESULTS:: NaB induced Smad3 in RIE-1 cells and in 4 human colon cancer cell lines. NaB enhanced TGF-beta-induced Smad3 phosphorylation and potentiated TGF-beta-induced PAI-1 expression. NaB and TGF-beta synergistically inhibited anchorage-independent growth of Akt-transformed RIE-1 cells. CONCLUSIONS:: These results demonstrate that NaB induces Smad3 and potentiates TGF-beta signaling and its tumor suppressor activity in gut epithelial cells. Our data reveal a novel molecular mechanism that may explain in part the beneficial effects of dietary fiber in decreasing the risk of colon cancers.


Meta-analysis of colonic reservoirs versus straight coloanal anastomosis after anterior resection (Br J Surg 2006; 93: 19-32).
Wille-Jorgensen P
Br J Surg. 2006 Apr 11;93(5):639.

Induction and recovery of colonic motility/defecatory disorders after extrinsic denervation of the colon and rectum in rats.
Shimizu K, Koda K, Kase Y, Satoh K, Seike K, Nishimura M, Kosugi C, Miyazaki M
Surgery. 2006 Mar;139(3):395-406.

BACKGROUND: Anterior resection for rectal disease is associated with extrinsic autonomic denervation of the neorectum, which may influence the myenteric plexus, and subsequently the motility/defecatory status after operation. METHODS: A rat model with denervated neorectum was constructed. Colonic contractile activity in vivo, the amount of generic neuron marker (PGP 9.5) and nitric oxide synthase (NOS) were measured periodically. The responses of the muscle strip in each period to electrical field stimulation were evaluated using various neurotransmitters. RESULTS: In rats with denervated neorectum, giant migrating contractions (GMCs) of the distal colon, the number of fecal lumps per day and their small size, significantly increased in the early phase postoperatively, although both recovered in the late-phase period. The contractile response of the muscle strip of the denervated colon to acetylcholine was reduced throughout the period; however, contraction of the denervated colon under the addition of NO inhibitor (l-NAME) was enhanced significantly in the late-phase period, and recovered to the control level by atropine. Neuronal NOS, but not PGP 9.5 concentration, in the myenteric plexus at the distal denervated colon, significantly increased in the late-phase period. None of the above items differed from the control at other colonic portions throughout the period. CONCLUSIONS: Extrinsic autonomic denervation causes abnormal hyper-motility in the neorectum, which may be associated with multiple evacuations in the early phase postoperatively. Increased acetylcholine and the subsequent increase of neuronal NOS in the myenteric plexus may be an adaptive mechanism to compensate for such abnormal colonic motility after extrinsic denervation.

Effects of an osmotically active agent on colonic transit.
Skoog SM, Bharucha AE, Camilleri M, Burton DD, Zinsmeister AR
Neurogastroenterol Motil. 2006 Apr;18(4):300-6.

It is unknown if sorbitol, a widely used laxative agent, accelerates colonic transit, and if these effects are modified by concomitant meal ingestion. Colonic transit was assessed by (111)In scintigraphy in 40 healthy subjects. After a 24-h scan, subjects received sorbitol (30 mL of 70% solution) or dextrose (30 mL of 70% solution), administered with or without a meal. Colonic transit, breath hydrogen excretion, and symptom scores were recorded for 4 h thereafter. VAS scores for flatulence, but not other symptoms increased (P = 0.004) by 13.1 +/- 6.3 mm (mean +/- SEM) on a 100 mm scale after sorbitol alone or sorbitol with a meal (by 18.9 +/- 7.2 mm), but not after dextrose. After adjusting for GC(24), sorbitol accelerated (P < 0.001) colonic transit (GC(28) = 3.0 +/- 0.3) compared with dextrose (GC(28) = 2.2 +/- 0.2), regardless of meal ingestion. Breath hydrogen excretion was correlated with the change in colonic transit (r = 0.52, P < 0.01) and with flatulence (r = 0.45, P = 0.003) after sugar ingestion. In healthy subjects, sorbitol accelerated colonic transit and increased flatulence but not other symptoms within 4 h, regardless of meal intake.

Functional Correlates of Anal Canal Anatomy: Puborectalis Muscle and Anal Canal Pressure.
Liu J, Guaderrama N, Nager CW, Pretorius DH, Master S, Mittal RK
Am J Gastroenterol. 2006 Apr 6;.

BACKGROUND: Resting and squeeze pressures in the anal canal are thought to reflect the contributions of the internal anal sphincter (IAS) and the external anal sphincter (EAS) respectively. Role of the puborectalis muscle (PRM) in the genesis of anal canal pressure is not known. OBJECTIVES: To determine the functional correlates of anal canal anatomy. METHODS: Seventeen asymptomatic nulliparous women were studied using simultaneous 3D ultrasound images and manometry of the anal canal. Ultrasound images were recorded using a transducer placed at the vaginal introitus and pressures were recorded with a side-hole manometry catheter using a station (every 5 mm) pull-through technique. Pressures were recorded at rest and during voluntary squeeze. RESULTS: Anal canal high pressure zone was 39 +/- 1 mm in length. The IAS, EAS, and PRM were clearly visualized in the ultrasound images. EAS was located in the distal (length 19 +/- 1 mm) and PRM in the proximal part (length 18 +/- 1 mm) of the anal canal. The station pull-through technique revealed increases in pressure with voluntary squeeze in the proximal as well as distal parts of the anal canal. Proximal anal canal pressure, located in the PRM zone, showed greater circumferential asymmetry than the distal anal canal pressure, located in the EAS zone. CONCLUSIONS: (1) PRM contributes to the squeeze pressure in the proximal part of the anal canal and EAS to the distal anal canal. (2) PRM squeeze-related increase in anal canal pressure might be important in the anal continence mechanism.

Intestinal gases and flatulence: Possible causes of occurrence.
Kurbel S, Kurbel B, Vcev A
Med Hypotheses. 2006 Mar 27;.

All gases entrapped in closed body cavities are destined to be partially or completely absorbed. Intestinal gases often accumulate and cause flatulence. This paper proposes a simple concept of intestinal gas occurrence based on our knowledge on gas resorption in other body cavities. Compliance of intestinal and abdominal walls makes pressure in the liquid chyme bubbles near 760mmHg. Intestinal gases are from three sources. Air can be swallowed, CO(2) come from the gastric acid neutralisation and from intestinal bacterial colonies that also produce hydrogen and methane. In continuously mixed liquid chyme, the total pressure of blood gases is similar or lower than in the venous blood (706), well below the bubble forming pressure (760mmHg). Some local production of bacterial gases with partial pressure of more than 90mmHg is required, so the resulting small bowel bubbles would contain less than 20% of bacterial gases. If peristaltic mixing of chyme is prevented by an obstacle, local pressures of bacterial gases build up, form bubbles that fuse and finally make X-ray visible aeroliquid levels. Bacterial gases make almost 3/4 of the flatulence. Formation of bubbles destined to become flatulence might depend on altered rheological condition of the large bowel content, with local abundant production of bacterial gases near bacterial colonies. Gases are unable to diffuse rapidly through the dense liquid content and local accumulation allows formation of bubbles mainly of bacterial gases. Their pressure can be higher 760mmHg, since they are stretching the thick content. Poor diffusion of gases keeps them almost free of blood gases and their entrance makes them bigger. As the content moves along the colon, the content is becoming more solid and gases are becoming entrapped in large bubbles. Some blood and bacterial gases are absorbed and exhaled, but the remaining quantity has no other escape except flatulence. Flatulence rich in bacterial gases might be the price for the large bowel water reabsorption. It seems that beside the peroral use of antibiotics active in the colon, little can be done to reduce flatulence.


[Imaging, anatomic, and surgical considerations for rectal organs and function following radical resection of a rectal carcinoma.]
Stelzner F, Biersack HJ, von Mallek D
Chirurg. 2006 Feb 22;.

The distal quarter of the rectum is derived from the cloaca and can be viewed as a specialized "sensory organ". Only the proximal three quarters of the rectum stem phylogenetically from intestinal tissues. Therefore, only this upper portion has an associated mesorectum. A significant amount of data support the notion that profound differences exist between the enterogenic, upper segments and the cloacogenic, lower segment of the rectum: 1. differing supply with blood and Iymph vessels, 2. embryologic and comparative anatomic findings, 3. the central support system provided by Denonvilliers' fascia, 4. specialized innervation, 5. malformations of the continence organ, 6. findings on magnetic resonance images and histologic macro sections, 7. findings on PET-CT images, 8. the muscular wall architecture of different portions of the rectum, 9. differences in basic function (storage vs continence), 10. location of most postoperative local recurrences of rectal carcinomas, even when complete mesorectal resection was performed, since hundred jears.

Functional outcome and quality of life in anorectal malformations.
Goyal A, Williams JM, Kenny SE, Lwin R, Baillie CT, Lamont GL, Turnock RR
J Pediatr Surg. 2006 Feb;41(2):318-22.

BACKGROUND/PURPOSE: The aim of this study was to assess the early functional outcome and quality of life (QOL) in children with anorectal malformations. METHODS: Children treated for anorectal malformations (ARMs) from 1994 to 2000 were evaluated if 4 years or older. Primary outcome measures were bowel function score, assessed by functional outcome questionnaire, and QOL using the Pediatric Quality of Life Inventory (PedsQL 4). The secondary outcome measure was age at potty training. Twenty healthy children were used as controls for functional outcome and age at potty training. Data are reported as mean (SD) unless otherwise stated. RESULTS: Eighty children were evaluated during the study period. The mean age at follow-up was 82 months (18.7). The response rate was 76.3% (58/76) for bowel function and 77.5% (62/80) for QOL questionnaires. Functional outcome score (maximum 20) decreased significantly with increasing severity of the ARM (male perineal fistula, 16 [3]; female perineal fistula, 15 [3]; rectourethral fistula, 12 [4]; vestibular fistula, 13 [3.5]; bladder neck fistula, 6 [2]; analysis of variance, P = .001). However, there was no difference in QOL between patients with ARM and controls. There was no correlation between age and either bowel function score (Pearson r2 = 0.06) or QOL (Pearson r(2) = 0.12). Affected children took significantly longer to achieve potty training for bladder (35 [13.8] months vs 26 [8.7] months for controls [t test, P = .005]) and bowels (38 [16] months vs 25 [7] months [t test, P = .001]). CONCLUSION: Children with ARMs have significantly worse bowel function than their peers, depending on the type of lesion. Despite these findings, QOL was not significantly impaired. No correlation was demonstrated between age and either functional outcome or QOL.

Transanal endoscopic-assisted proctoplasty--a novel surgical approach for individual management of patients with imperforate anus without fistula.
Pakarinen MP, Baillie C, Koivusalo A, Rintala RJ
J Pediatr Surg. 2006 Feb;41(2):314-7.

BACKGROUND/AIM: Imperforate anus without fistula consists of a spectrum of defects with variable distance between the rectal pouch and the perineum. We have developed a novel surgical approach for individual management of these patients based on precise knowledge of the level of the anomaly. METHODS: All consecutive patients with imperforate anus without fistula between 2002 and 2004 had sigmoidostomy performed after having failed to pass meconium in the first 24 hours. The upper pouch was intraluminally visualized using retrograde endoscopy through the sigmoid mucous fistula. The distal termination of the rectum was clearly identified as by convergence of the anal columns. Bright translumination of the endoscope light from the rectum to the anal dimple within the external sphincter indicated a low malformation amenable to transanal proctoplasty. The rectum was incised from below under endoscopic visual control. Poor translumination indicated a higher defect, in which case, the operation was converted to standard posterior sagittal anorectoplasty. RESULTS: Seven patients (6 boys) were identified. Four patients (3 boys) completed transanal endoscopic-assisted proctoplasty. In all cases, the convergence of anal columns indicating rectal termination was right above the anal pit at the site of the maximal external sphincter squeeze. In 3 patients, the operation was converted to posterior sagittal anorectoplasty after verification of a higher anomaly by endoscopy. There were no operative complications. The median follow-up was 3 months (range, 1-26 months). All patients have an appropriate size anus and regular bowel actions. CONCLUSIONS: Transanal endoscopic-assisted proctoplasty allows safe and anatomical reconstruction of the anorectum, as well as contemporaneous closure of the sigmoidostomy in a significant proportion of patients with imperforate anus without fistula, avoiding the potential complications associated with the open posterior sagittal approach.

Anal Electrical Stimulation With Long Pulses Increases Anal Sphincter Pressure in Conscious Dogs.
Nie Y, Pasricha JP, Chen JD
Dis Colon Rectum. 2006 Feb 13;.
PURPOSE: This study was designed to investigate the effects and mechanisms of anal electric stimulation with long pulses on anal sphincter pressure in conscious dogs. METHODS: The study was performed after enema in nine healthy female hound dogs and composed of four randomized sessions ("dose"-response, anal electric stimulation only, or with atropine or phentolamine). The anal sphincter pressure was measured by using manometry and quantified by using the area under the contractile curve (mmHg/sec). Anal electric stimulation was performed via a pair of ring electrodes attached to a manometric catheter. The stimulation parameters in all but dose-response sessions included a frequency of 20 ppm, pulse width of 200 ms, and amplitude of 3 mA. RESULTS: The anal sphincter pressure was 55.7 +/- 6 at baseline and increased by 37 percent to 76.4 +/- 6.5 during electric stimulation (P = 0.009). The increase of anal pressure during stimulation was positively correlated with the stimulation energy (r = 0.395; P < 0.01). The excitatory effect of electric stimulation was sustained for at least 20 minutes. Atropine did not alter anal pressure and did not abolish the excitatory effect of anal electric stimulation on the sphincter. Phentolamine reduced anal pressure from the baseline value of 50.5 +/- 4.7 to 33.1 +/- 5.4 (P = 0.019). The electric stimulation induced increase in anal pressure was dropped from 19 +/- 2.6 to 9.9 +/- 2.8 (P = 0.029) at the presence of phentolamine. CONCLUSIONS: Anal electric stimulation with long pulses increases anal sphincter pressure in an energy-dependent manner. The alpha-adrenergic but not the cholinergic pathway at least partially mediates the excitatory effect of anal electric stimulation.


Comparison of Rectoanal Axial Forces in Health and Functional Defecatory Disorders.
Bharucha AE, Croak AJ, Gebhart JB, Berglund LJ, Seide BM, Zinsmeister AR, An KN
Am J Physiol Gastrointest Liver Physiol. 2006 Feb 2;.

Anal manometry measures circumferential pressures, but not axial forces, which are responsible for defecation and contribute to fecal continence. Our aims were to investigate these mechanisms by measuring axial rectoanal forces with an intra-rectal sphere or a latex balloon, fixed at 8, 6, or 4 cm from the anal verge, and connected to axial force and displacement transducers. Rectoanal forces and rectal pressures within a latex balloon were measured at baseline (i.e., at rest) and during maneuvers (i.e., squeeze, simulated evacuation, and a Valsalva maneuver) in 12 asymptomatic women and 12 women with symptoms of difficult defecation. Anal resting and squeeze pressures were also assessed by manometry and were similar in controls and patients. At rest, axial rectoanal forces were directed inward and increased as the device approached the anal verge. Controls augmented this inward force when they squeezed and exerted an outward force during simulated expulsion and a Valsalva maneuver. The force change during maneuvers was also affected by device location and was highest at 4 cm from the verge. In patients, the force at rest and the change in force during all maneuvers was lower than in controls. The rectal pressure during a Valsalva maneuver was also lower in patients than in controls, suggestive of impaired propulsion. In conclusion, a subset of women with defecatory symptoms had weaker axial forces not only during expulsion but also during a Valsalva maneuver and when they squeezed (i.e., contracted) their pelvic floor muscles, suggestive of generalized pelvic floor weakness.

Three-dimensional transperineal ultrasonography for evaluation of the anal sphincter complex: another dimension in understanding peripartum sphincter trauma.
Yagel S, Valsky DV
Ultrasound Obstet Gynecol. 2006 Feb;27(2):119-123.

Ano-rectal motility responses to pelvic, hypogastric and pudendal nerve stimulation in the Gottingen minipig.
Andersen IS, Buntzen S, Rijkhoff NJ, Dalmose AL, Djurhuus JC, Laurberg S
Neurogastroenterol Motil. 2006 Feb;18(2):153-61.

We investigated the effect of efferent stimulation of the pelvic (PN), hypogastric (HGN) and pudendal (PuN) nerves on ano-rectal motility in Gottingen minipigs using an impedance planimetry probe. Changes in the rectal cross-sectional area (CSA) at five axial positions and pressures in the rectum and anal canal were investigated simultaneously. Pelvic nerve stimulation elicited a CSA decrease in the proximal part of the rectum and a simultaneous CSA increase in its distal part. Anal pressure also decreased. Hypogastric nerve and PuN stimulation elicited an increase in anal pressure, but no rectal response. Severing the HGN produced a persistent reduction in resting anal pressure, but no change was observed when the PN and the PuN were severed. Stimulation of the distal part of all three nerves produced a persistent response. Administration of phentolamine and pancouronium eliminated the response to stimulation of the HGN and the PuN, respectively. Conclusion: Rectal responses to PN stimulation vary more than previously suggested. The HGN has an excitatory effect on the internal anal sphincter, and the PuN on the external anal sphincter. However, the PuN plays no major role in maintaining basal anal pressure.

Numerical distribution of lymphoid nodules in the human sigmoid colon, rectosigmoidal junction, rectum, and anal canal.
Cameron IL, Kent JE, Philo R, Barnes CJ, Hardman WE
Clin Anat. 2006 Jan 27;.

There is little information on the numerical distribution of lymphoid nodules (LN) in distal segments of the human large bowel. A novel approach was therefore developed to assess the number of LN in the sigmoid colon, the rectosigmoid segment, the rectum, and the anal canal in humans. The distal large bowel from five cadavers was selected for quantitative study. The number of LN was scored macroscopically from the proximal sigmoid colon to the distal anal canal. A numerical distribution, previously unreported, consisting of two circular bands of LN was observed in each of the five cadavers. One band was located 3 cm proximal from the pectinate line and the other was located at the rectosigmoid segment. Significantly more LN occurred 3-5 cm proximal to the pectinate line compared to areas distal or proximal to this band of LN. This band of LN has not been reported previously in humans.

Bacterial and fungal microbiota in relation to probiotic therapy (VSL#3) in pouchitis.
Kuehbacher T, Ott SJ, Helwig U, Mimura T, Rizzello F, Kleessen B, Gionchetti P, Blaut M, Campieri M, Folsch UR, Kamm MA, Schreiber S
Gut. 2006 Jan 9;.

BACKGROUND: The intestinal microbiota plays a critical role in the pathophysiology of pouchitis, a major complication after ileal pouch anal anastomosis in patients with ulcerative colitis. Recently, controlled trials have demonstrated that probiotics are effective in the maintenance of remission in pouchitis patients. However, the mechanism of efficacy for a therapy with probiotics remains elusive. This study explores the role of the bacterial and fungal flora in a controlled trial for remission maintenance of pouchitis with the probiotic VSL#3 compound. METHODS: The mucosa-associated pouch microbiota before and after therapy with VSL#3 was investigated by analysis of endoscopic biopsies using ribosomal DNA/RNA- based community fingerprint analysis, clone libraries, real-time PCR, and fluorescence in-situ hybridization (FISH). Patients were recruited from a placebo-controlled remission maintenance trial with VSL#3. RESULTS: Patients who developed pouchitis while treated with placebo had a low bacterial and a high fungal diversity. Bacterial diversity was increased and fungal diversity was reduced in patients in remission maintained with VSL#3 (p=0.001). Real-time PCR experiments demonstrated that VSL#3 increased the total number of bacterial cells (p=0.002) and modified the spectrum of bacteria towards anaerobic species. Taxa- specific clone libraries for Lactobacilli and Bifidobacteria showed that the richness and spectrum of these bacteria were altered under probiotic therapy. CONCLUSIONS: Probiotic therapy with VSL#3 increases the total number of intestinal bacterial cells as well as richness and diversity of the bacterial microbiota, especially the anaerobic flora. The diversity of the fungal flora is repressed. Restoration of the integity of a "protective" intestinal mucosa-related microbiota could be therefore a potential mechanism of probiotic bacteria in inflammatiory barrier diseases of the lower gastrointestinal tract.

Role of the rectosigmoidal junction in fecal continence: concept of the primary continent mechanism.
Shafik A, Shafik AA, El Sibai O, Ahmed I, Mostafa RM
Arch Surg. 2006 Jan;141(1):23-6.

HYPOTHESIS: At mass contraction of the descending colon, the colonic contents stop at the sigmoid colon (SC) and do not pass directly to the rectum. We investigated the hypothesis that a continent mechanism seems to exist at the rectosigmoidal junction (RSJ), preventing the direct passage of stools from the descending colon to the rectum. METHODS: The SC in 16 healthy volunteers (mean +/- SD age, 38.6 +/- 10.2 years; 9 men and 7 women) was distended with an isotonic sodium chloride solution-filled balloon, and the pressure response of the RSJ and the rectum was recorded at rapid and gradual filling of the balloon. The test was repeated after the SC and RSJ were anesthetized separately. RESULTS: Rapid SC balloon distension with a mean +/- SD of 52.1 +/- 3.6 mL of isotonic sodium chloride solution effected an RSJ pressure increase to a mean +/- SD of 67.8 +/- 18.4 cm H(2)O (P<.01) with no rectal pressure response (P>.05). Slow SC filling produced a progressive increase in RSJ pressure but no rectal pressure change. At a mean +/- SD SC distending volume of 86.3 +/- 4.1 mL, the RSJ pressure decreased to 9.6 +/- 2.8 (P<.01), and the balloon was dispelled to the rectum; rectal pressure increased (P<.001), and the balloon was expelled to the exterior. The RSJ pressure did not respond to distension of the anesthetized SC. CONCLUSIONS: Contraction of the RSJ at rapid SC distension with big volumes implies a reflex relationship that we call the RSJ guarding reflex. This reflex seems to prevent the descending colon contents from passing directly to the rectum. It is considered the first continent reflex and may serve as an investigative tool in the study of fecal incontinence.