Role of nitric oxide in the left-sided colon of patients with diverticular disease

BACKGROUND/AIMS: Non-adrenergic non-cholinergic inhibitory nerves are the most important nerves in the enteric nervous system of the human gut. Recently, it has been established that nitric oxide is released by stimulation of non-adrenergic non-cholinergic inhibitory nerves. Therefore, in order to evaluate the function of nitric oxide in the left-sided colon of patients with diverticular disease, we examined the enteric nerve responses in colonic tissues from patients with this disease, and also used the left-sided normal colon as a control. METHODOLOGY: Colonic tissue specimens (the diverticular bearing segments) were obtained from 9 patients with diverticular disease of the left-sided colon, and normal segments of the left-sided colon were obtained from 16 patients with ascending colon cancer. A mechanograph was used to evaluate in vitro colonic responses to electrical field stimulation of adrenergic and cholinergic nerve before and after treatments with various autonomic nerve blockers, NG-nitro-L-arginine, and L-arginine. RESULTS: 1) The diverticular colon was more strongly innervated by cholinergic nerves than the normal colon (P < 0.01); 2) Non-adrenergic non-cholinergic inhibitory nerves were found to act on the normal colon and to a lesser extent in the diverticular colon (P < 0.05). 3) Nitric oxide mediates the relaxation reaction of non-adrenergic non-cholinergic inhibitory nerves in the normal colon and to a lesser extent in the diverticular colon. CONCLUSIONS: These findings suggest that the intrinsic intestinal innervation contains excitatory and inhibitory nerves and that the former, especially cholinergic nerves, are dominant in the left-sided colon with diverticula. In addition, diminution of action of non-adrenergic non-cholinergic inhibitory nerves by substances such as nitric oxide may be largely related to the high intraluminal pressure by colonic segmentation observed in the left-sided colon with diverticula.     

Ng-nitro-L-arginine reduces nonadrenergic, noncholinergic relaxations of human gut.

The aim of this study was to determine whether nonadrenergic, noncholinergic inhibitory neurotransmission in human circular sigmoid colonic and internal anal sphincter muscle involves release of a nitric oxide-like substance. Colonic and sphincter muscle respond to electrical field stimulation by giving nonadrenergic, noncholinergic relaxations. After-contractions always occur in colonic muscle but only sometimes in sphincter muscle. Ng-Nitro-L-arginine abolished relaxations of sphincter muscle and partially reduced those of colonic muscle. After-contractions were undiminished as were relaxations of sphincter muscle to sodium nitroprusside. The effects of Ng-nitro-L-arginine were reversed by L-arginine. The results suggest that nitric oxide is possibly the neurotransmitter mediating nonadrenergic, noncholinergic relaxations of the human internal anal sphincter muscle.     

The effects of neurotensin in the colon of patients with slow transit constipation

BACKGROUND/AIMS: The cause of dysmotility in the colon of patients with slow transit constipation (STC) is still unknown. Neurotensin (NT) has recently been shown to be a neurotransmitter in the non-adrenergic non-cholinergic (NANC) excitatory nerves of the human alimentary tract. To clarify the physiological significance of NT in the colon of patients with STC, we examined the enteric nerve responses in lesional and normal bowel segments derived from patients with STC and patients who underwent colon resection for colonic cancers. METHODOLOGY: Twenty-eight preparations were taken from colonic lesions in 10 patients with slow transit constipation (2 men and 8 women, aged 23 to 70 years, mean 46.3 years). Forty-six preparations were taken from the normal colons of 16 patients with colonic cancer (8 men and 8 women, aged 40 to 66 years, mean 50.1 years). A mechanographic technique was used to evaluate in vitro muscle responses to electrical field stimulation (EFS) before and after treatment with various autonomic nerve blockers and NT. RESULTS: After blocking both the adrenergic and cholinergic nerves (Experiment 1), NT showed contraction reaction on both normal and STC colons in a concentration-dependent manner. The contraction reactions to NT in the normal colon were more dominant than those in the STC colon. There were significant differences between the frequency of contraction reactions to NT in normal colon strips and those in STC colon strips (P < 0.001). Following addition of tetrodotoxin (Experiment II), all muscle strips of normal and STC colons demonstrated contraction responses by NT. The effects of NT in the normal and STC colon muscle strips were essentially the same as in experiment 1, although the extent of contraction was somewhat diminished. CONCLUSIONS: Those results suggested that NT acts both via NANC excitatory nerves and also directly on the colonic smooth muscle. A decrease of NT mediates NANC excitatory nerves and plays an important role in the dysmotility observed in the colons of patients with STC.     

Are there any functional differences of nitric oxide between the transitional segment in Hirschsprung's disease and the diseased colon in hypoganglionosis?

BACKGROUND/AIMS: In histological studies, there are no significant differences between the transitional segment (TS) of Hirschsprung's disease (HD) and the diseased segment in patients with hypoganglionosis (Hypo). In contrast, there are no reports whether or not TS show impaired motility like Hypo. Nitric oxide (NO) has recently been shown to be a neurotransmitter in the non-adrenergic noncholinergic (NANC) inhibitory nerves in the human gut. To clarify the significance of NO in TS and Hypo, enteric nervous responses in colonic tissue obtained from TS and Hypo were investigated. METHODOLOGY: This study investigated responses of the enteric nervous system including NANC inhibitory nerves in colonic tissue obtained from TS in 10 patients with HD (8 boys and 2 girls, aged from 6 months to 2 years) and diseased colon in 6 patients with Hypo (6 boys, aged from 6 months to 2 years). Normal colons obtained from patients with HD and Hypo (n = 16) were used as controls. Mechanography was used to evaluate in vitro colonic responses to electrical field stimulation (EFS) of adrenergic and cholinergic nerves before and after treatments with various autonomic nerve blockers, N(G)-monomethyl-L-arginine (L-NMMA), and L-arginine. RESULTS: Non-adrenergic non-cholinergic (NANC) inhibitory nerves were found to act on the normal colon and to a lesser extent both in the TS and Hypo. In addition, there were no significant differences between the TS and Hypo. Nitric oxide (NO) mediates the relaxation reaction of the NANC inhibitory nerve in the normal colon and to a lesser extent both in the TS and Hypo. In addition, there were no significant difference between the TS and Hypo. CONCLUSIONS: Diminution of NO mediation of NANC inhibitory nerves may be largely related to the impaired motility observed in patients with TS and diseased colon of Hypo.     

Idiopathic chronic constipation is associated with decreased colonic vasoactive intestinal peptide

To investigate the reported association between idiopathic chronic constipation and morphologic abnormalities of enteric nerves, we measured the concentrations of six neuropeptides, vasoactive intestinal peptide, peptide histidine-methionine, substance P, methionine5-enkephalin, neuropeptide Y, and the bombesinlike intestinal peptides, in descending colon from 4 patients with idiopathic chronic constipation. Decreased concentrations of vasoactive intestinal peptide (707 +/- 112 ng/g wet tissue) and peptide histidine-methionine (543 +/- 58 ng/g) were found in the muscularis externa obtained from constipated patients compared with normal concentrations (40 patients) of vasoactive intestinal peptide (1199 +/- 47 ng/g) and peptide histidine-methionine (815 +/- 45 ng/g). Vasoactive intestinal peptide was identified by immunocytochemistry in nerve fibers within the circular smooth muscle layer of descending colon obtained from 6 control patients, but not in nerve fibers within the circular smooth muscle of descending colon obtained from 3 patients with idiopathic chronic constipation. By contrast, the distribution of immunoreactive met5-enkephalin was similar in normal descending colon and in descending colon obtained from patients with idiopathic chronic constipation. Decreased colonic concentrations of vasoactive intestinal peptide (a candidate nonadrenergic, noncholinergic inhibitory neurotransmitter) may be associated with diminution of inhibitory innervation of colonic circular smooth muscle in some patients with idiopathic chronic constipation.     

Role of non-adrenergic non-cholinergic inhibitory nerves in the colon of patients with ulcerative colitis

The cause of impaired colonic motility in patients with ulcerative colitis (UC) is unknown. The non-adrenergic non-cholinergic (NANC) inhibitory nervous system is one of the most important factors in the enteric nervous system of human gut. To assess the physiological significance of NANC inhibitory nerves in the colon of patients with UC, we investigated the enteric nerve responses of colonic tissues from patients with this disease. Colonic tissues were obtained from the lesional sigmoid colons of six patients with UC. Normal sigmoid colonic tissues obtained from ten patients with colonic cancer were used as controls. A mechanographic technique was used to evaluate in-vitro muscle responses to the electrical field stimulation (EFS) of adrenergic and cholinergic nerves before and after treatment with various autonomic nerve blockers. NANC inhibitory nerves were found to act on both normal colon and the lesional colon of patients with UC, but colon with UC was more strongly innervated by NANC inhibitory nerves than was the normal colon. These findings suggest that NANC inhibitory nerves play an important role in the impaired motility observed in the colon of patients with UC. Received Feb. 3, 1997; accepted May 23, 1997     

The role of nitric oxide (NO) in the human internal anal sphincter

Purpose. Nitric oxide (NO) has recently been shown to be a neurotransmitter in nonadrenergic noncholinergic (NANC) inhibitory nerves in the human gut. To clarify the physiological significance of NO in the human internal anal sphincter (IAS), we investigated enteric nervous responses in normal IAS muscle strips above the dentate line, obtained from patients with rectal cancer. Methods. Normal IAS muscle strips above the dentate line, obtained from ten patients who underwent rectal amputation for low rectal cancers were used. The subjects consisted of eight men and two women, aged from 46–72 years (mean age, 54.2 years). A mechanographic technique was used to evaluate in-vitro IAS muscle responses to electrical field stimulation (EFS) of adrenergic and cholinergic nerves before and after treatment with various autonomic nerve blockers, N^G-nitro-l-arginine (l-NNA) and l-arginine. Results. Excitatory nerves were mainly involved in the regulation of enteric nerve responses to EFS in the baseline condition of the study, and NANC inhibitory nerves acted on the normal IAS. l-NNA concentration-dependently inhibited the relaxation in response to EFS in the human IAS, and this inhibitory effect in the IAS was reversed by l-arginine. Conclusions. These findings suggest that NANC inhibitory nerves play important roles in regulating relaxation of the human IAS, and that NO plays an important role as a neurotransmitter in NANC inhibitory nerves of the human IAS. Received: September 7, 2000 / Accepted: January 12, 2001     

Treatment of severe and intractable constipation

Opinion statement A careful clinical evaluation, exclusion of secondary causes (eg, colonic obstruction, metabolic conditions [hypothyroidism, hypercalcemia], and drug-induced constipation), and assessments of colonic transit and rectal evacuation are necessary to ascertain whether constipation is attributable to normal colonic transit, delayed colonic transit (ie, slow-transit constipation), or a rectal evacuation disorder (with or without delayed colonic transit). Idiopathic slow-transit constipation is a clinical syndrome predominantly affecting women and is characterized by intractable constipation and delayed colonic transit. This syndrome is attributed to disordered colonic motor function and spans a spectrum of variable severity ranging from patients who have relatively mild delays in transit, but are otherwise indistinguishable from irritable bowel syndrome, at one extreme to patients with colonic inertia or chronic megacolon at the other extreme. Most patients are treated with one or more pharmacological agent. A subtotal colectomy is effective and occasionally indicated for patients with medically refractory severe slow-transit constipation, provided that pelvic floor dysfunction has been excluded or treated. Pelvic floor dysfunction can be diagnosed by the clinical features and anorectal testing. Most patients with pelvic floor dysfunction will respond to pelvic floor retraining by biofeedback therapy.     

Regulation of the enteric nervous system in the colon of patients with slow transit constipation

BACKGROUND/AIMS: The cause of impaired motility in patients with slow transit constipation is unknown. To clarify the physiological significance of cholinergic, adrenergic, non-adrenergic non-cholinergic inhibitory nerves in the colon of patients with slow transit constipation, we investigated the enteric nerve responses on lesional and normal bowel segments derived from patients with slow transit constipation and patients who underwent colon resection for colonic cancers. METHODOLOGY: Twenty preparations were taken from the lesional colon of 6 patients with slow transit constipation (2 men and 4 women, aged 23 to 68 years, with a mean age of 44.0 years). Thirty-six preparations were taken from the normal colon of 12 patients with colonic cancer (6 men and 6 women, aged 40 to 60 years, with a mean age of 52.2 years). A mechanographic technique was used to evaluate in vitro muscle responses to acetylcholine, adrenalin, electrical field stimulation of adrenergic and cholinergic nerves before and after treatment with various autonomic nerve blockers. RESULTS: The contraction reaction to acetylcholine in the colon with slow transit constipation was significantly weaker than in the normal colon (P < 0.01). The relaxation reaction to adrenalin in the colon with slow transit constipation was stronger than in the normal colon. The colon with slow transit constipation was more strongly innervated by non-adrenergic non-cholinergic inhibitory nerves than the normal colon, significantly (P < 0.05). CONCLUSIONS: These findings suggest that a decrease of cholinergic nerve and an increase of non-adrenergic non-cholinergic inhibitory nerve play an important role in the impaired motility observed in the colon of patients with slow transit constipation.     

Abnormal colonic propagated activity in patients with slow transit constipation and constipation-predominant irritable bowel syndrome

BACKGROUND: The pathophysiological basis of constipation is still unclear, and the role of colonic dysfunction is debated, especially in irritable bowel syndrome. Objective data are quite scarce, especially concerning colonic propulsive activity. AIMS: To evaluate high- and low-amplitude colonic propulsive activity in constipated patients (slow-transit type and irritable bowel syndrome) in comparison with normal controls. PATIENTS AND METHODS: Forty-five constipated patients (35 with slow-transit constipation and 10 with constipation-predominant irritable bowel syndrome) were recruited, and their data compared to those of 18 healthy subjects. Twenty-four-hour colonic manometric recordings were obtained in the three groups of subjects, and data concerning high- and low-amplitude colonic propulsive activity were then compared. RESULTS: High-amplitude propagated contractions were significantly (p < 0.05) decreased in patients with slow-transit constipation and constipation-predominant irritable bowel syndrome with respect to controls (1.5 +/- 0.4, 3.7 +/- 2, and 6 +/- 1 events/subject/day, respectively). In slow-transit constipation, a significant decrease of contractions' amplitude was also observed. Concerning low-amplitude propagated contractions, patients with slow-transit constipation had significantly less events with respect to patients with constipation-predominant irritable bowel syndrome (46 +/- 7 vs. 87.4 +/- 19, p = 0.015); no differences were found between patients with slow-transit constipation and controls and between patients with constipation-predominant irritable bowel syndrome and controls. All three groups displayed a significant increase of low-amplitude propagated contractions after meals (6.3 +/- 2 vs. 18.2 +/- 5 for controls, p < 0.005; 6.4 +/- 1.4 vs. 16.3 +/- 2.4 for slow-transit constipation, p < 0.005; 10.5 +/- 3.2 vs. 32.6 +/- 7 for constipation-predominant irritable bowel syndrome, p = 0.001). CONCLUSIONS: Low-amplitude propagated contractions may represent an important physiologic motor event in constipated patients, reducing the severity of constipation in patients with irritable bowel syndrome and preserving a residual colonic propulsive activity in patients with slow-transit constipation.     

Airway autonomic nervous system dysfunction and asthma]

Airways are richly innervated by 4 nervous systems, namely adrenergic, cholinergic, inhibitory nonadrenergic noncholinergic (i-NANC), and excitatory NANC (e-NANC) nervous systems. Dysfunction or hyperfunction of these systems may be involved in the inflammation or airway hyperresponsiveness observed in asthmatic patients. The cholinergic nervous system is the predominant neural bronchoconstrictor pathway in humans. Airway inflammation shows exaggerated acetylcholine release from cholinergic nerves via dysfunction of the autoreceptor, muscarinic M2, which is possibly caused by major basic protein or IgE. Vasoactive intestinal peptide (VIP) and nitric oxide (NO) released from i-NANC nerves act as an airway smooth muscle dilator. The effects of VIP and NO are diminished after allergic reaction by inflammatory cell-mediated tryptase and reactive oxygen species. Thus, in asthmatic airways, the inflammatory change-mediated neural imbalance may result in airway hyperresponsiveness. Tachykinins derived from e-NANC nerves have a variety of actions including airway smooth muscle contraction, mucus secretion, vascular leakage, and neutrophil attachment, and may be involved in the pathogenesis of asthma. Since tachykinin receptor antagonists are effective for bradykinin- and exercise-induced bronchoconstriction in asthmatic patients, these drugs may be useful for asthma therapy.     

Nitric oxide production is diminished in colonic circular muscle from acquired megacolon

PURPOSE: Nitric oxide modulates human colonic smooth muscle function. To determine whether nitric oxide production is altered in colon from acquired megacolon, we measured cholinergic nerve-mediated contractionsin vitro before and after inhibition of nitric oxide synthase. METHODS: Intramural nerves in circular smooth muscle from histologically normal colon (n=12) and acquired megacolon (n=3) were activated by electrical field stimulation. RESULTS: In controls blockade of nitric oxide synthase by N^G-Nitro-L-Arginine induced increases (P<0.05) in amplitude of contractions; these increases in amplitudes were blocked by L-Arginine (analysis of variance;P<0.05). By contrast, blockade of nitric oxide synthase did not increase amplitudes of contractions with circular smooth muscle from acquired megacolon. An immediate phasic contraction was blocked by atropine sulfate. CONCLUSIONS: The results support the concept that nitric oxide production modulates cholinergic nerve-mediated contractions in normal colonic circular muscle, whereas acquired megacolon is associated with altered release of this inhibitory neurochemical. Potential explanations include depletion of tissue L-Arginine, decreased capacity to recycle citrulline to arginine, or decreased release of vasoactive intestinal peptide from circular smooth muscle in acquired megacolon.Supported by Veterans Administration Medical Research Funds and by West Virginia University.Presented at Digestive Disease Week, Washington, D.C., May 11 to 14, 1997.     

Role of nitric oxide signal transduction pathway in regulation of vascular tone.

Nitric oxide signal transduction pathway has been detected in a number of cell types including vascular endothelial cells, smooth muscle cells, and noncholinergic nonadrenergic nerve endings. Nitric oxide synthase is a key enzyme which produces nitric oxide from L-arginine. Three different types of this enzyme have been described: constitutive soluble, inducible soluble, and constitutive particulate. Nitric oxide is a lipophilic molecule that can rapidly diffuse through biological membranes. It provides communication between endothelial and smooth muscle cells as well as between nerve endings and smooth muscle cells. Decreased production of nitric oxide may lead to vasospasm, whereas its overproduction may cause pathological vasodilatation. Understanding of the role of nitric oxide signal transduction pathway in regulation of vascular tone will facilitate design of better strategies for the prevention and treatment of vascular diseases.     

Physiological studies on nitric oxide in the lower esophageal sphincter of patients with reflux esophagitis

BACKGROUND/AIMS: Nitric oxide has recently been shown to be a neurotransmitter in the non-adrenergic non-cholinergic inhibitory nerves in the digestive tract. To clarify the significance of nitric oxide in the lower esophageal sphincter of patients with reflux esophagitis, we have investigated enteric nerve responses in lower esophageal sphincter specimens obtained from the patients with gastric cancer who had reflux esophagitis, using the normal lower esophageal sphincter as a control. METHODOLOGY: Lower esophageal sphincter specimens were obtained from 6 patients who had gastric cancer with reflux esophagitis, and normal lower esophageal sphincter specimens were obtained from 12 patients who had gastric cancer without gastroesophageal reflux disease. A mechanograph was used to evaluate in vitro lower esophageal sphincter muscle responses to electrical field stimulation of the adrenergic and cholinergic nerves before and after treatment with various autonomic nerve blockers, and NG-nitro-L-arginine and L-arginine. RESULTS: 1) Cholinergic nerves were more dominant in the normal lower esophageal sphincter than in the lower esophageal sphincter with reflux esophagitis (p < 0.01); 2) non-adrenergic non-cholinergic inhibitory nerves were significantly found to act more on the lower esophageal sphincter with reflux esophagitis than those in the normal lower esophageal sphincter (p < 0.01); 3) nitric oxide mediates the relaxation reaction via non-adrenergic non-cholinergic inhibitory nerves in the normal lower esophageal sphincter and the lower esophageal sphincter with reflux esophagitis; 4) The relaxation reaction of nitric oxide was observed in the normal lower esophageal sphincter and increased in the lower esophageal sphincter with reflux esophagitis. CONCLUSIONS: These findings suggest that the cholinergic and non-adrenergic non-cholinergic inhibitory nerves play important roles in regulating contraction and relaxation of the human lower esophageal sphincter, and nitric oxide plays an important role in non-adrenergic non-cholinergic inhibitory nerves of the human lower esophageal sphincter. In addition, a decrease of the action of cholinergic nerves and an increase of the action of non-adrenergic non-cholinergic inhibitory nerves by nitric oxide may be largely related to the low lower esophageal sphincter pressure observed in the patients with reflux esophagitis.     

A Novel Surgical Approach to Slow-Transit Constipation: Report of Two Cases

Introduction Slow-transit constipation after proper diagnosis and extensive medical therapy may have a surgical solution. Total abdominal colectomy and ileorectal anastomosis, at our institution, is the surgical procedure of choice. Nonetheless, patients may reject this alternative because of morbidity. Discussion We report two cases of slow-transit constipation diagnosed after a thorough investigation with two colonic transit tests showing slow-transit constipation, a normal anorectal manometry, balloon expulsion test, small-bowel follow-through, defecography, laboratory and psychologic tests. The patients rejected standard surgical treatment (total colectomy + ileorectal anastomosis). A colonic bypass with an ileorectal anastomosis, leaving the colon in situ, was offered and accepted by the two patients. This was performed laparoscopically liberating the cecum and terminal ileum, transecting the terminal ileum through a small suprapubic incision, and anastomosing the terminal ileum to the rectosigmoid junction intracorporeally. The total surgical time was 50 and 60 minutes, respectively. Summary Both patients made uneventful recoveries and were discharged on the fourth postoperative day. They have completed four and two months of close follow-up and at present have one to four bowel movements per day with mild abdominal distension and pain. To our knowledge this is the first report of colonic bypass for the treatment of slow-transit constipation. Reprints are not available.     

Integrity of cholinergic innervation to the lower esophageal sphincter in achalasia

The human lower esophageal sphincter (LES) is believed to be innervated by nonadrenergic, noncholinergic inhibitory nerves, and cholinergic excitatory nerves. In idiopathic achalasia, LES relaxation is abnormal because the inhibitory nerves to the sphincter are either absent or functionally impaired. The integrity of cholinergic excitatory nerves to the LES, however, has not been thoroughly evaluated. In 27 patients with untreated idiopathic achalasia, and 21 healthy volunteers, we investigated the hypothesis that postganglionic cholinergic nerves to the LES are functionally intact in achalasia. The LES responses to atropine, edrophonium, methacholine, amyl nitrite, and pentagastrin were assessed. In 2 achalasia patients, patterns of fasting motor activity in the LES were investigated during overnight manometric studies. Resting LES pressure was significantly greater in the achalasia patients, 41 +/- 4 mmHg (mean +/- SE), than in the normal subjects, 20 +/- 2 mmHg. Atropine significantly reduced LES pressure in both groups by 30%-75%. Edrophonium increased LES pressure in the achalasia patients but had negligible effect on the normal subjects. The LES in achalasia patients exhibited an increased sensitivity to both methacholine and pentagastrin compared with the normal subjects. In both patients who underwent an overnight manometric study, the LES exhibited cyclic phasic contractile activity synchronous with gastric contractions during the migrating motor complex. We conclude that the study findings support the hypothesis that postganglionic cholinergic LES innervation in achalasia patients is either normal or only minimally impaired, in contrast to the marked impairment of the inhibitory nerves governing LES relaxation.     

Decreased interstitial cell of cajal volume in patients with slow-transit constipation

BACKGROUND & AIMS: The cause of slow-transit constipation is incompletely understood. Recent observations suggest a central role for interstitial cells of Cajal in the control of intestinal motility. The aim of this study was to determine the volume of interstitial cells of Cajal in the normal sigmoid colon and in the sigmoid colon from patients with slow transit constipation. METHODS: Sigmoid colonic samples were stained with antibodies to protein gene product 9.5, c-Kit, and alpha-smooth muscle actin. Three-dimensional reconstruction of regions of interest was performed using consecutive images collected on a laser scanning confocal microscope and ANALYZE software. RESULTS: Volume of interstitial cells of Cajal was significantly decreased in all layers of sigmoid colonic specimens from patients with slow-transit constipation compared with normal controls. Neuronal structures within the colonic circular smooth muscle layer were also decreased. CONCLUSIONS: A decrease in the volume of interstitial cells of Cajal may play an important role in the pathophysiology of slow-transit constipation.     

Slow-transit constipation

INTRODUCTION: Autonomic neuropathy is thought to play a role in the pathogenesis of slow-transit constipation, but other gastrointestinal organs may also be involved, even if they are symptom-free. We investigated whether motility in gastrointestinal organs other than the colon was impaired in patients with slow-transit constipation and whether the autonomic nervous system was involved. METHODS: Twenty-one consecutive patients (18 females; median age, 46 years) with severe chronic constipation (< or = 2 defecations/week and delayed colonic transit time) were studied. Autonomic neuropathy function was tested with esophageal manometry, gastric and gallbladder emptying (fasting and postprandial motility) by ultrasonography, orocecal transit time (H2-breath test), colonic transit time (radiopaque markers), and anorectal volumetric manometry. The integrity of the autonomic nervous system was assessed by a quantitative sweat-spot test for preganglionic and postganglionic fibers, tilt-table test, and Valsalva electrocardiogram R-R ratio. RESULTS: Esophageal manometry showed gastroesophageal reflux or absence of peristalsis in five of the seven patients examined. Gallbladder dysmotility (i.e., increased fasting, postprandial residual volume, or both) was observed in 6 of 14 (43 percent) patients. Gastric emptying was decreased in 13 of 17 (76 percent) patients. Orocecal transit time was delayed in 18 of 20 (90 percent) patients; median transit time was 160 (range, 90-200) minutes. Median colonic transit time was 97 (range, 64-140) hours. Anorectal function showed abnormal rectoanal inhibitory reflex and decreased rectal sensitivity in 11 of 19 (58 percent) patients. Signs of autonomic neuropathy of the sympathetic cholinergic system were found in 14 of 18 (78 percent) patients. Only one of nine patients had vagal abnormalities detected with the Valsalva test and four of five patients with a history of orthostatic hypotension had a positive tilt-table test. CONCLUSIONS: Slow-transit constipation may be associated with impaired function of other gastrointestinal organs. More than 70 percent of patients with slow-transit constipation present some degree of autonomic neuropathy. Severe constipation may be the main complaint in patients with a systemic disease involving several organs and possibly involving the autonomic nervous system. This should be considered in the management of such cases.     

Abnormal Colonic Endocrine Cells in Patients with Chronic Idiopathic Slow-Transit Constipation

Background: The aim of the present study was to investigate the colonic endocrine cells in patients with slow-transit constipation, to ascertain the presence of a possible abnormality. Methods: Ten patients with chronic slow-transit constipation were investigated. As controls, macroscopically and histologically normal tissues from the colon of 12 patients were examined. These patients had polyps, prolapsis, chronic diverticulitis, volvulus, and haemorrhoids. The endocrine cells were stained by immunocytochemistry and quantified by computerized image analysis. Results: There were significantly fewer enteroglucagon- and serotonin-immunoreactive cells in patients with chronic slow-transit constipation. There was no statistically significant difference between patients and controls with regard to the number of peptide YY (PYY)-, pancreatic polypeptide (PP)-, and somatostatin-immunoreactive cells. The cell secretory indexes (CSI) of enteroglucagon- and somatostatin-immunoreactive cells were significantly decreased. There was no statistically significant difference in the CSI between the patients and controls with regard to PYY-, PP-, and serotonin-immunoreactive cells. Conclusion: The changes in colonic endocrine cells in patients with slow-transit constipation may be one cause of the decreased motility in the colon and consequent development of constipation.     

Abnormal colonic endocrine cells in patients with chronic idiopathic slow-transit constipation

BACKGROUND: The aim of the present study was to investigate the colonic endocrine cells in patients with slow-transit constipation, to ascertain the presence of a possible abnormality. METHODS: Ten patients with chronic slow-transit constipation were investigated. As controls, macroscopically and histologically normal tissues from the colon of 12 patients were examined. These patients had polyps, prolapsis, chronic diverticulitis, volvulus, and haemorrhoids. The endocrine cells were stained by immunocytochemistry and quantified by computerized image analysis. RESULTS: There were significantly fewer enteroglucagon- and serotonin-immunoreactive cells in patients with chronic slow-transit constipation. There was no statistically significant difference between patients and controls with regard to the number of peptide YY (PYY)-, pancreatic polypeptide (PP)-, and somatostatin-immunoreactive cells. The cell secretory indexes (CSI) of enteroglucagon- and somatostatin-immunoreactive cells were significantly decreased. There was no statistically significant difference in the CSI between the patients and controls with regard to PYY-, PP-, and serotonin-immunoreactive cells. CONCLUSION: The changes in colonic endocrine cells in patients with slow-transit constipation may be one cause of the decreased motility in the colon and consequent development of constipation.