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Purpose: This study was designed to investigate the changes in rectal compliance and tone during anal electric stimulation and the involvement of the alpha-adrenergic pathway in conscious dogs., Methods: Eight healthy dogs were studied in five randomized sessions. Anal sphincter pressure was quantified by using the area under the contractile curve. Rectal compliance and tone were measured in a pressure-controlled phasic and isobaric distention by using an electronic barostat. Anal electric stimulation was performed via a pair of ring electrodes attached to the catheter., Results: The electric stimulation-induced increase in sphincter pressure was lowered by the presence of an alpha(1)-adrenergic receptor antagonist, prazosin (18.6 +/- 7.4 vs. 45.4 +/- 9.7, P < 0.05), or alpha(2)-adrenergic receptor antagonist, yohimbine (10.2 +/- 8.2 vs. 38.3 +/- 7.6, P < 0.05), compared with the control. The threshold volume in rectoanal inhibitory reflex during electric stimulation was significantly higher than during baseline (27.5 +/- 0.9 vs. 22.5 +/- 1.9 ml, P < 0.05). There were no significant differences between the percentage drops in sphincter pressure with and without stimulation at a rectal distention level of 45 ml of air. Anal electric stimulation significantly increased rectal compliance reflected as reduced P(1/2) (11.1 +/- 1.5 vs. 16.7 +/- 1.1, P = 0.027) and reduced kappa (11.6 +/- 2.5 vs. 20.5 +/- 2.6, P = 0.0095), compared with the control session, but did not significantly alter rectal tone., Conclusions: Anal electric stimulation increases anal sphincter pressure, mediated at least partially by the alpha-adrenergic pathway. It also increases rectal compliance but does not alter rectal anal inhibitory reflexes.

Purpose: Autonomic dysreflexia is a common and potentially dangerous hypertensive response to stimulation below the level of injury that occurs in patients with spinal cord injury at T6 or above. Rectosigmoid distention and anal manipulation are among the stimuli that may precipitate autonomic dysreflexia. Instillation of topical local anesthetic into the rectum is the recommended prophylaxis against autonomic dysreflexia of anorectal origin. However, a previous randomized, double-blind, placebo-controlled trial showed that topical lidocaine in the rectum does not blunt the autonomic dysreflexia response to anorectal procedures. The purpose of this study was to determine whether lidocaine anal sphincter block would be effective in limiting anorectal procedure-associated autonomic dysreflexia., Methods: We enrolled patients with chronic, complete spinal cord injury above T6, who were having anorectal procedures (flexible sigmoidoscopy and/or anoscopic hemorrhoid ligation). In a double-blind fashion, patients were randomized for intersphincteric anal block with 1 percent lidocaine or normal saline (placebo) before the procedure. Blood pressure was measured before, during, and after the block and procedure., Results: Thirteen patients received lidocaine, and 13 received placebo. The groups were similar in age, level of injury, duration of spinal cord injury, type of procedure, and procedure duration. The mean maximal systolic blood pressure increase for the lidocaine group was 22 +/- 14 mmHg, significantly lower than the placebo group's 47 +/- 31 mmHg (P = 0.01)., Conclusions: Lidocaine anal block significantly limits the autonomic dysreflexia response in susceptible patients undergoing anorectal procedures.

Purpose: Pharmacologic treatments are gaining widespread acceptance as first-line therapy for anal fissure. However, existing treatments have limited clinical usefulness because of side effects and incomplete healing rates., Methods: Fresh human surgical resection specimens containing internal anal sphincter and rectal circular muscle were collected. Strips of smooth muscle were cut from each muscle group and mounted in a superfusion organ bath. The effects of increasing concentrations of phosphodiesterase inhibitors were evaluated., Results: All phosphodiesterase inhibitors tested caused a dose-dependent reduction in the tone of the internal anal sphincter, with potencies as follows: vinpocentine (phosphodiesterase-1 inhibitor; 50 percent maximum inhibition concentration = 0.87 +/- 0.10 microM), erythro-9-(2-hydroxy-3-nonyl) adenine hydrochloride (phosphodiesterase-2 inhibitor; 32 +/- 4.8 microM), trequinsin (phosphodiesterase-3 inhibitor; 0.28 +/- 0.041 microM), rolipram (phosphodiesterase-4 inhibitor; 63 +/- 9 microM), zaprinast (phosphodiesterase-1,5,6,9,11 inhibitor; 3 +/- 0.69 microM), and dipyridamole (phosphodiesterase-5,6,8,10,11 inhibitor; 5.5 +/- 2 microM). Although all inhibitors were also effective on rectal circular muscle strips, erythro-9-(2-hydroxy-3-nonyl) adenine hydrochloride, trequinsin, and rolipram were at least an order of magnitude more potent in this tissue than in the internal anal sphincter., Conclusions: There are several functionally important phosphodiesterases in the internal anal sphincter and rectal circular muscle. Both adenosine 3', 5'-cyclic monophosphate and guanosine 3',5'-cyclic monophosphate appear to be important in the myogenic tone of the internal anal sphincter, and this study provides further evidence of the sphincteric specialization of this tissue. Phosphodiesterase inhibitors might represent a new therapy for the treatment of anal fissure.

Purpose: Infliximab has been reported to improve fistulizing Crohn's disease. Moreover, prompt healing of mucosal ulcers has been described. Whether fistulas disappear or remainders of fistulas persist is unknown. This study documents fistulous tracts before and after infliximab therapy by means of hydrogen peroxide-enhanced endosonography, Methods: Eight patients with perianal, vaginal, or perineal fistulas were treated with a triplet of infliximab 5 mg/kg infusions. At baseline, and at Week 4 after the last infusion, fistulas were documented by local inspection, digital examination, and hydrogen peroxide-enhanced anal or vaginal endosonography., Results: Patients with vaginal or perineal fistulas did not respond clinically to therapy, whereas patients with perianal fistulas improved considerably. However, in all patents remainders of fistulous tracts were demonstrated by endosonographic techniques., Conclusions: Short-term treatment of Crohn's disease-associated fistulas with infliximab does not induce disappearance of fistulous tracts, irrespective of therapeutic response.

Purpose: Known risk factors for the development of colorectal dysplasia or cancer in ulcerative colitis are total colonic involvement and long duration of the disease. It has recently been suggested that presence of primary sclerosing cholangitis is another independent risk factor-especially for proximal colorectal dysplasia or cancer-and that treatment with sulfasalazine might reduce the frequency of colorectal cancer in ulcerative colitis; the present study was undertaken to shed light on the validity of these theories., Methods: A total of 143 patients with ulcerative colitis underwent regular colonoscopies and multiple biopsies in a 20-year surveillance program for studies of long-standing total ulcerative colitis. Fifty-one of the patients developed colorectal dysplasia or cancer. Patient records were scrutinized retrospectively for information of presence of primary sclerosing cholangitis, site of the colorectal malignancy, and results of sulfasalazine treatment., Results: Nineteen of the patients had primary sclerosing cholangitis; these ran a significantly higher risk of developing colorectal dysplasia or cancer than patients with ulcerative colitis only. All colorectal cancers (n = 3) and 75 percent of all colorectal dysplasias or cancers among patients with primary sclerosing cholangitis were located in the proximal part of the colon, whereas 36 percent were found in that same region among the patients with ulcerative colitis without primary sclerosing cholangitis (P = 0.02). Sulfasalazine treatment showed no significant protective effect on the development of colorectal dysplasia or cancer in patients with ulcerative colitis., Conclusion: The risk evaluation, as assessed by multivariate analysis, shows that primary sclerosing cholangitis proves to be an additional and independent risk factor for the development of colorectal dysplasia or cancer in patients with ulcerative colitis-particularly in the proximal part of the colon. The findings do not support the theory that sulfasalazine treatment exerts a protective effect against colorectal dysplasia or cancer.

Purpose: The rectum possesses electric activity in the form of pacesetter and action potentials. In a recent study we suggested that the waves are not initiated by the extra-rectal autonomic innervation but might be triggered by a "rectosigmoid pacemaker." It was postulated that the electric signals are transmitted in the rectal wall through either the muscle bundles or enteric nerve plexus. This hypothesis was studied., Methods: Under anesthesia the abdomens of 15 dogs were opened, and three electrodes were applied to the rectal serosa. Rectal electric activity and pressure were recorded. Rectal denervation was produced by bilateral pelvic ganglionectomy. The effect of adrenergic (phentolamine and propranolol) and cholinergic (atropine sulfate) blocking agents and a smooth-muscle relaxant (drotaverine) on the electromechanical activity of the denervated rectum was evaluated., Results: After pelvic ganglionectomy rectal pressure decreased (P<0.05), and pacesetter and action potentials exhibited irregular rhythm and amplitude, a condition of "rectoarrhythmia." The arrhythmic pattern showed no significant change (P>0.05) on administration of the adrenergic and cholinergic blocking agents. However, it was abolished when drotaverine was given., Conclusion: Electric waves in the rectal wall seem to be transmitted through the muscle bundles and not the enteric nerve plexus, a finding that might assist in developing an appropriate pharmacotherapy for rectal dysmotilities and defecation disorders.

Introduction: Glyceryl trinitrate reduces anal resting pressure and aids the healing of anal fissures. However, some patients develop tachyphylaxis and the fissure fails to heal, suggesting that other agents are needed. This study assesses the effects of nifedipine (a calcium channel antagonist) in modulating resting tone and agonist-induced contractions in human internal anal sphincter (IAS) and rectal circular muscle., Methods: Smooth muscle strips from the IAS and rectal circular muscle from ten patients undergoing surgical resection were mounted for isometric tension recording in a superfusion organ bath. The effects of noradrenaline and carbachol were assessed in the presence of various perfusates., Results: LAS strips developed tone and spontaneous activity. Noradrenaline produced dose-dependent contractions. In calcium-free Krebs solution, tone and activity were abolished and no contractions were elicited in response to noradrenaline. Nifedipine also abolished tone and spontaneous activity, but contractions to noradrenaline were only slightly attenuated. In contrast, rectal smooth muscle strips developed spontaneous activity but no resting tone and contracted in response to carbachol. In calcium-free Krebs solution, the spontaneous activity and carbachol contractions were abolished. Addition of nifedipine to the perfusate abolished spontaneous activity and greatly reduced contractions., Discussion: These data suggest that spontaneous activity and resting tone are dependent on extracellular calcium and flux across the cells. Agonist-induced contraction in the IAS is attributable mainly to the release of calcium from intracellular stores, whereas rectal circular smooth muscle depends principally on extracellular calcium entering the cell for contraction. The attenuation of contractions in both tissues and the abolition of resting tone in the IAS suggest that nifedipine may be useful in the management of patients with anorectal disorders.

Unlabelled: Not much is known about the specific pathophysiologic mechanisms of soiling. Although the causes of soiling may vary, it is mostly associated with anorectal disorders that can deform the contour of the anus and anal canal. In most cases, this disorder can be treated successfully by medical or surgical therapy. If this appropriate treatment is not available or fails, reconstruction of the contour deformity of the anus by perianal (submucosal) injection of soft tissue bulking agents may be successful., Purpose: The main purpose of this pilot study was to evaluate locoregional reaction and distant migration after local perianal injection of solid polydimethylsiloxane elastomer particles (Bioplastique implants)., Methods: Twelve Lewis rats received a local perianal injection of Bioplastique implants. Six of them received an additional perianal injection of gentamicin. Six weeks after injection, the rats were euthanized., Results: Microscopically, the local tissue reaction was that of a quiescent foreign body reacting with encapsulation. Microscopic examinations could not reveal any migration to locoregional lymph nodes, liver, spleen, lungs, or brain., Conclusion: We conclude that, because of minimum local reaction and lack of evidence of distant migration, polydimethylsiloxane elastomer particle paste (Bioplastique implants) seems to be a potentially safe substance for local perianal injection.

Unlabelled: Instillation of 4 percent formalin effectively treats radiation hemorrhagic proctitis; however, little is known regarding its side effects., Purpose: The study contained herein was undertaken to determine rectal compliance and collagen content, mucosal and vascular histologic changes, and kinetics of formalin absorption following instillation., Methods: Fifteen mongrel dogs (50-60 pounds) were randomized into five experimental groups according to time elapsed from formalin treatment: control, acute, one week, two weeks, and four weeks. Formalin was instilled in 30-ml aliquots to a total volume of 400 ml. Rectal compliance (closed manometry system) was assessed pre-formalin and post-formalin at the designated time interval. Serum formalin metabolites were determined at time 0, 0.5, 1, and 3 hours. A segment of rectal wall was analyzed for collagen content, mucosal injury, and blood vessel density., Results: Serum formalin levels peaked within 30 minutes, returning to normal by 3 hours. With the exception of one dog, toxic levels were not reached at any time during the study. No dogs experienced sepsis, fever, or altered gastrointestinal function. Acute and one-week dogs showed mild diffuse proctitis and mucosal slough, which healed within two weeks. Rectal compliance and collagen content were unchanged. Mucosal blood vessels decreased in number early (P = 0.03)., Conclusions: Instillation of 4 percent formalin in sequential aliquots of a small volume that is kept in contact for a short period of time is safe. Serum formalin levels generally do not reach toxic levels, and the slight elevation in formalin concentration that was seen returns to normal within three hours. Formalin-induced proctitis heals within two weeks, and no long-term changes in rectal compliance or collagen content were seen.

Purpose: A study was performed to evaluate the antiproliferative effects of low doses of the nonsteroidal drug, sulindac, on adenomas and rectal mucosa in familial adenomatous polyposis and to analyze the influence on tumor-suppressor genes and on apoptosis., Methods: This was a prospective, controlled, nonrandomized Phase II dose-finding study for sulindac. The study group (n = 28) and control group (n = 10) underwent colectomy and ileorectal anastomoses, with repeated proctoscopy with endoluminal ultrasound and biopsies every three months. Dose-reduction of sulindac according to adenoma reversion was predetermined. Proliferation marker, Ki-67 (MIB1 and 5), on frozen or paraffin sections evaluated the antiproliferative effects; mutant p21ras, pantropic p53, mutant p53, and anti-bcl-2 were performed as enzyme-linked immunosorbent assay procedures and/or immunohistochemistry on paraffin sections., Results: All patients responded to sulindac after 24 weeks (at the latest). There was a significant reduction of adenomas and dose reduction to 67 mg/day after three years of therapy (Mann's test for trend, P < 0.001). Results consisted of 78 percent complete reversions, 22 percent partial reversions of adenomas at latest re-examination, and no influence on upper gastrointestinal tract adenomas. No influence was detected on repeated hemograms, liver, or renal function at high or low doses. There was a permanent antiproliferative effect (Ki-67) of low-dose sulindac, significant blocking of ras mutation activation, and a significant difference of untreated and treated mucosa in mutant p53 content (Wilcoxon's or Kruskal-Wallis each, P < 0.05). Reverse correlation of anti-bcl-2 and p53 immunostaining on mucosa sections was an indication of adenoma relapse., Conclusions: Low-dose antiproliferative sulindac therapy is highly effective in adenoma reversion in familial adenomatous polyposis patients. Sulindac shows influence on tumor-suppressor genes and on apoptosis markers. An immunostaining correlation indicates adenoma relapse in flat microadenomas in advance of macroscopic appearance. Low-dose sulindac treatment may develop into an additive permnanent therapy for colectomized familial adenomatous polyposis patients.

Purpose: This study was designed to investigate the role of nitric oxide in neurogenic relaxation of the longitudinal layer of human rectal smooth muscle., Methods: Tissue was obtained from the mid rectum of patients undergoing anterior resection for carcinoma. Adjacent strips of longitudinal muscle were dissected and mounted in organ baths for isometric tension recording. In preliminary experiments to determine the response of strips to cholinergic, adrenergic, and potential excitatory agonists, strips were superfused with standard Krebs solution (37 +/- 0.5 degrees C; pH, 7.4 +/- 0.05). Investigation of inhibitory, nonadrenergic noncholinergic responses required the addition of 3 x 10(-6) M histamine to induce reproducible and stable tension for five-minute "test" periods, during which electrical field stimulation (EFS) and additional drugs were applied. In these experiments, strips were superfused with Krebs solution that contained atropine sulfate (3 x 10(-6) M) and guanethidine (3 x 10(-6) M)., Results: The response to cholinergic and adrenergic agonists was typical of nonsphincter specialized gastrointestinal smooth muscle. EFS elicited frequency-dependent, neurogenic (tetrodotoxin-sensitive) relaxations of precontracted strips, which were reduced in dose-dependent fashion by addition of N omega-nitro-L-arginine and restored by addition of 3 x 10(-4) M L-arginine but not by D-arginine. Addition of exogenous nitric oxide (sodium nitroprusside) mimicked the relaxant response induced by EFS., Conclusion: Smooth muscle from the longitudinal layer of human rectum receives an intrinsic inhibitory innervation mediated by nitric oxide.

Background and Purpose: The intestine is rich in peptidergic innervation, which modulates mucosal immune responses. Among neuropeptides, substance P (SubP) has received considerable attention for stimulatory effects on various immunocytes in inflammatory diseases. In our prior study, we demonstrated increased innervation of SubP containing nerve fibers (SubP fibers) in ulcerative colitis (UC) surgically resected colonic specimens. In the present study, we examined the alterations of SubP fibers among various subgroups of UC, divided according to clinicopathologic features., Methods: Distribution of SubP fibers were examined immunohistochemically in the rectal biopsy specimens of UC. The UC group was further divided into subgroups according to six clinicopathologic parameters. The linear density of SubP fibers was measured by digitalized morphometry for quantitative analysis., Results: Multivariate analysis revealed significant correlations between linear density of SubP fibers vs. activity of diseases and total dose of prednisolone. Linear density was significantly increased in active cases of UC (active UC, 22.6 +/- 1.6 microm/1,000 microm2; vs. inactive UC, 12.2 +/- 0.8 microm/1,000 microm2; P < 0.01). Furthermore, the increase was pronounced in cases that showed persistent inflammation and, accordingly, needed a high dose or continuous administration of prednisolone., Conclusion: Alterations in SubP fibers appear to play an important role in the pathogenesis of UC.

Purpose: The somatostatin analog, octreotide, has previously been found to influence rectal sensation and may also influence anal resting pressure., Methods: We studied the effect of octreotide on anal resting pressure and rectal compliance in eight healthy patients. Octreotide was administered intravenously as a bolus injection in doses of 100 and 10 micrograms or as infusion of 250 micrograms/hour on separate days and compared with placebo., Results: Within one minute after a bolus injection of 100 micrograms of octreotide, anal resting pressure increased from 56 +/- 12 to 96 +/- 16 cm H2O (P < 0.005). Octrotide had no effect on rectal sensitivity or compliance measurements. Octreotide counteracted rectoanal reflex by increasing anal pressure almost to the level found with an empty rectum., Conclusion: Somatostatin thus seems to contribute to the regulation of rectoanal reflex.

Purpose: This study was designed to investigate whether nitric oxide mediates inhibitory innervation in human rectal circular smooth muscle., Methods: Tissue was obtained from the midrectum of patients undergoing anterior resection for carcinoma. Adjacent strips of circular muscle were dissected and mounted in superfusion organ baths for isometric tension recording and initially loaded with 1 g of weight. Strips were continuously bathed with standard Krebs solution (37 degrees C, bubbled with 97 percent O2/3 percent CO2) containing 3 X X 10(-6) M guanethidine and 3 X 10(-6) M atropine sulfate to block adrenergic and muscarinic cholinergic neurotransmission. After equilibration, strips had no intrinsic tone, and reproducible and stable tension was, therefore, induced by the addition of 3 X 10 M histamine for five-minute "test" periods, during which electrical field stimulation (EFS) and additional drugs were applied., Results: EFS elicited frequency-dependent, neurogenic (tetrodotoxin-sensitive) relaxations of precontracted strips. Addition of N-w-nitro-L-arginine, a powerful competitive inhibitor of nitric oxide synthase, reduced the relaxant response to EFS in a dose-dependent fashion, and effect reversed by addition of s X 10(-4) M L-arginine but not by D-arginine. Addition of exogenous nitric oxide (sodium nitroprusside) mimicked the relaxant response induced by EFT., Conclusions: Human rectal circular smooth muscle receives an intrinsic inhibitory innervation mediated by nitric oxide. The presennce of a residual response following blockade of the enzyme nitric oxide synthase suggests the involvement of additional neurotransmitters.

Purpose: Based on the rationale that the calcium channel blocker, nifedipine, decreases lower esophageal sphincter pressure in achalasia, a prospective controlled trial was performed to evaluate the effect of sublingual nifedipine on the anal sphincter of controls and patients with high anal resting pressures., Methods: Ten age-matched and sex-matched controls without evidence of anal disorder and ten patients with hemorrhoids and/or fissure-in-ano were included in the study. Anorectal manometry, with an eight-channel, water-perfused catheter was performed on all patients before and 30 minutes after administration of 20 mg of sublingual nifedipine., Results: Nifedipine significantly reduced anal resting pressure in both controls and patients by approximately 30 percent (P < 0.001 and P < 0.0001, respectively). A significant reduction was also noted in the length of high-pressure zone of the anal sphincter (P < 0.02 for both groups) and in the frequency (controls, P < 0.05; patients, P < 0.03) and amplitude (controls, P < 0.03; patients, P < 0.009) of slow waves in both groups, whereas the presence, frequency, and amplitude of ultraslow waves were significantly reduced only in the patient group (P < 0.05; P < 0.01; P < 0.0005, respectively)., Conclusion: Nifedipine reduces the activity of the internal anal sphincter both in controls and patients with high anal resting pressure. The drug might be of some use in relieving symptoms in patients with hemorrhoids or anal fissure.

Purpose: Fecal electrolytes and organic anion concentrations are altered in ulcerative colitis, presumably reflecting changes in colon epithelial transport. Information of mucosal absorption of butyrate in active ulcerative proctosigmoiditis is not available., Methods: Dialysis bags containing 70 mmol/liter of butyrate in an isotonic electrolyte solution were placed in the rectum for 30 minutes. Net absorption or secretion rates of butyrate, lactate, and electrolytes were determined in the rectum of 12 patients with active ulcerative colitis (UC) and in 10 patients with quiescent UC and then compared with 10 healthy controls., Results: Net flux rates demonstrated a considerable absorption of butyrate in patients with active inflammation of 7.5 +/- 0.4 mumol/cm2/h and quiescent colitis of 6.6 +/- 0.4 mumol/cm2/h, equal to absorption in healthy controls of 6.3 +/- 0.5 mumol/cm2/h, P = 0.12. Despite normal butyrate absorption, sodium absorption was compromised in active ulcerative colitis (11.5 +/- 1.4 mumol/cm2/h) compared with quiescent (15.4 +/- 1.0 mumol/cm2/h) and controls (18.7 +/- 0.8 mumol/cm2/h) (P = 0.0006). Mucosal secretion of L-lactate was minimal in both healthy controls and quiescent UC but significantly increased in patients with proctosigmoiditis (0.2 +/- 0.1 mumol/cm2/h, 0.2 +/- 0.1 mumol/cm2/h vs. 0.9 +/- 0.2 mumol/cm2/h; P = 0.0001). Appearance of D-lactate was negligible in all three groups., Conclusions: This study demonstrates that rectal butyrate absorption is normal in UC, and it follows that butyrate supplied in enemas can be expected to be absorbed. The inflamed colonic mucosa secretes L-lactate, and the increased fecal lactate concentrations can be explained by mucosal origin of lactate.

Unlabelled: Ribose-cysteine (RibCys) is a prodrug of L-cysteine that stimulates glutathione biosynthesis. Increased glutathione levels have been shown to have a protective effect against radiation-induced injury and oxidative stress. Surface oximetry has previously been used successfully to predict anastomotic leakage., Purpose: The following study was done to evaluate the protective effect of RibCys and the predictive value of PtO2 determinations in a swine model., Methods: Domestic swine were divided into three groups: Group A served as a nonradiated control; Group B received 6,000 to 6,500 rad to the rectosigmoid; and Group C received RibCys (1 g/kg) prior to receiving 6,000 to 6,500 rad. Radiated animals and controls underwent rectosigmoid resection after a three-week rest period. Intraoperative anastomotic PtO2 was checked with a modified Clark electrode. Anastomoses were evaluated radiographically at three and seven days; animals were sacrificed, and bursting strength was recorded at 10 days., Results: Mean bursting pressures were 243.8 +/- 59.4, 199.5 +/- 37.8, and 209.5 +/- 54.9 mmHg (NS) for Groups A, B, and C, respectively. Anastomotic PtO2 ranged from 19 to 98 mmHg and could not be correlated with anastomotic leaks or bursting pressure. There were 11/15 radiation-related deaths and leaks (eight deaths and three leaks) in the radiated group and 4/12 radiation-related deaths and leaks (three deaths and one leak) in the group receiving radiation and RibCys (P < 0.04)., Conclusions: 1) RibCys protected animals against radiation-related deaths and anastomotic leaks following high doses of pelvic irradiation; 2) anastomotic PtO2 levels did not correlate with anastomotic healing in this model.

The objective of this study was to investigate the effects of the opioid loperamide and its recently synthesized pharmacologically inactive prodrug loperamide oxide on the anal sphincter. In a double-blind, placebo-controlled crossover study, anorectal manometry was performed in 12 healthy volunteers five hours after oral bolus application of 10 mg of loperamide, loperamide oxide, or placebo. Loperamide significantly increased the threshold volumes for minimal perception and urgency to defecate (P less than 0.05) and raised the volume required to abolish recovery of the rectoanal inhibitory reflex (P less than 0.05). These findings suggest that loperamide has a specific continence-improving action on the anal sphincter. However, anal resting pressure and maximal squeeze pressure were unaffected in our study and do not seem to be responsible for this effect. The effects under loperamide oxide showed a similar tendency but were without statistical significance.

Twelve mongrel dogs had superficial and deep colon biopsies above and below the peritoneal reflection. Six of the animals were given a barium enema; two had a barium enema immediately, two in three days, and two in six days. The animals were sacrificed 48 hours after the barium enema; the sigmoid was removed and tissue was examined macroscopically and microscopically. When healing rates of the biopsy sites were compared with those of control animals, there was no difference. The results suggest that barium has no deleterious effect on the healing of superficial or deep colorectal biopsies.

The aspect of the rectal mucosa after administration of hypertonic enemas is occasionally confused with the macroscopic appearance of quiescent ulcerative colitis. Criteria for a diagnosis of enema reaction were derived from a retrospective series and tested prospectively on 11 healthy volunteers. Photographs and biopsies were obtained before and after administration of a sodium phosphate hypertonic enema. Three observers evaluated blindly the "before" and "after" macroscopic and microscopic pictures, graded the features, and made an overall diagnosis. In random studies, two observers mistakenly classified a macroscopic picture, but all correct histologic diagnoses of "before" and "after" biopsies. In decreasing order of discriminating power, the following features of an enema reaction were found to be useful: separation and mucous depletion of the glands (no observer variation), increase in mucosal fragility in 91 per cent of cases (82--100 per cent), edema of the lamina propria in 88 per cent (73--100 per cent), straightening of the basal membrane in 82 per cent (73--91 per cent) and an increase in extruded mucus in 70 per cent (18--100 per cent). In 39 per cent of cases (36--45 per cent), erythrocytes appeared focally in the lamina propria. The effects of hypertonic enemas can be recognized on biopsy.

Histologic and ultrastructural examination of specimens of rectal mucosa from 11 patients who had recently consumed excessive quantities of alcohol revealed marked pathologic changes. Goblet cells were decreased and a dense mononuclear cell infiltrate was seen on light microscopic study. Electron microscopy revealed swollen, distorted mitochondria and dilated and vesicular endoplasmic reticulum. These abnormalities disappeared after two weeks' abstinence. It is suggested that disordered organelle structure and function might contribute to the diarrhea frequently observed following excessive alcohol intake.