Ischemic or toxic injury: A challenging diagnosis and treatment of drug-induced stenosis of the sigmoid colon.

A 48-year-old woman was admitted with 15-mo history of abdominal pain, diarrhea and hematochezia, and 5-mo history of defecation difficulty. She had been successively admitted to nine hospitals, with an initial diagnosis of inflammatory bowel disease with stenotic sigmoid colon. Findings from computed tomography virtual colonoscopy, radiography with meglumine diatrizoate, endoscopic balloon dilatation, metallic stent implantation and later overall colonoscopy, coupled with the newfound knowledge of compound Qingdai pill-taking, led to a subsequent diagnosis of ischemic or toxic bowel disease with sigmoid colon stenosis. The patient was successfully treated by laparoscopic sigmoid colectomy, and postoperative pathological examination revealed ischemic or toxic injury of the sigmoid colon, providing a final diagnosis of drug-induced sigmoid colon stenosis. This case highlights that adequate awareness of drug-induced colon stenosis has a decisive role in avoiding misdiagnosis and mistreatment. The diagnostic and therapeutic experiences learnt from this case suggest that endoscopic balloon expansion and colonic metallic stent implantation as bridge treatments were demonstrated as crucial for the differential diagnosis of benign colonic stenosis. Skillful surgical technique and appropriate perioperative management helped to ensure the safety of our patient in subsequent surgery after long-term use of glucocorticoids.

Isoosmolar enemas demonstrate preferential gastrointestinal distribution, safety, and acceptability compared with hyperosmolar and hypoosmolar enemas as a potential delivery vehicle for rectal microbicides.

Rectally applied antiretroviral microbicides for preexposure prophylaxis (PrEP) of HIV infection are currently in development. Since enemas (rectal douches) are commonly used by men who have sex with men prior to receptive anal intercourse, a microbicide enema could enhance PrEP adherence by fitting seamlessly within the usual sexual practices. We assessed the distribution, safety, and acceptability of three enema types-hyperosmolar (Fleet), hypoosmolar (distilled water), and isoosmolar (Normosol-R)-in a crossover design. Nine men received each enema type in random order. Enemas were radiolabeled [(99m)Tc-diethylene triamine pentaacetic acid (DTPA)] to assess enema distribution in the colon using single photon emission computed tomography/computed tomography (SPECT/CT) imaging. Plasma (99m)Tc-DTPA indicated mucosal permeability. Sigmoidoscopic colon tissue biopsies were taken to assess injury as well as tissue penetration of the (99m)Tc-DTPA. Acceptability was assessed after each product use and at the end of the study. SPECT/CT imaging showed that the isoosmolar enema had greater proximal colonic distribution (up to the splenic flexure) and greater luminal and colon tissue concentrations of (99m)Tc-DTPA when compared to the other enemas (p<0.01). Colon biopsies also showed that only the hyperosmolar enema caused sloughing of the colonic epithelium (p<0.05). In permeability testing, the hypoosmolar enema had higher plasma (99m)Tc-DTPA 24-h area under the concentration-time curve and peak concentration compared to the hyperosmolar and isoosmolar enemas, respectively. Acceptability was generally good with no clear preferences among the three enema types. The isoosmolar enema was superior or similar to the other enemas in all categories and is a good candidate for further development as a rectal microbicide vehicle.

Design and in vitro evaluation of formulations with pH and transit time controlled sigmoidal release profile for colon-specific delivery.

The primary objective of the study was to develop a pH and transit time controlled sigmoidal release polymeric matrix for colon-specific delivery of indomethacin. Tablet matrices were prepared using a combination of hydrophilic polymers (polycarbophil or carbopol) having pH-sensitive swelling properties with hydrophobic polymer ethyl cellulose. The prepared matrices were characterized for physical properties and in vitro release kinetics. The presence of ethyl cellulose in a hydrophilic polymer matrix resulted in a sigmoidal in vitro drug release pattern with negligible-to-very low drug release in the initial phase (0-6 h) followed by controlled release for 14-16 h. The retardation in initial release can be attributed to the presence of ethyl cellulose that reduced swelling of hydrophilic polymer(s), while in the later portion, polymer relaxation at alkaline pH due to the ionization of acrylic acid units on carbopol and polycarbophil resulted in enhanced drug release. Thus, a sigmoidal release pattern was obtained that could be ideal for colonic delivery of indomethacin in the potential treatment of colon cancer.

Purinergic and nitrergic junction potential in the human colon.

The aim of the present work is to investigate a putative junction transmission [nitric oxide (NO) and ATP] in the human colon and to characterize the electrophysiological and mechanical responses that might explain different functions from both neurotransmitters. Muscle bath and microelectrode techniques were performed on human colonic circular muscle strips. The NO donor sodium nitroprusside (10 microM), but not the P2Y receptor agonist adenosine 5'-O-2-thiodiphosphate (10 microM), was able to cause a sustained relaxation. NG-nitro-L-arginine (L-NNA) (1 mM), a NO synthase inhibitor, but not 2'-deoxy-N6-methyl adenosine 3',5'-diphosphate tetraammonium salt (MRS 2179) (10 microM), a P2Y antagonist, increased spontaneous motility. Electrical field stimulation (EFS) at 1 Hz caused fast inhibitory junction potentials (fIJPs) and a relaxation sensitive to MRS 2179 (10 microM). EFS at higher frequencies (5 Hz) showed biphasic IJP with fast hyperpolarization sensitive to MRS 2179 followed by sustained hyperpolarization sensitive to L-NNA; both drugs were needed to fully block the EFS relaxation at 2 and 5 Hz. Two consecutive single pulses induced MRS 2179-sensitive fIJPs that showed a rundown. The rundown mechanism was not dependent on the degree of hyperpolarization and was present after incubation with L-NNA (1 mM), hexamethonium (100 microM), MRS 2179 (1 microM), and NF023 (10 microM). We concluded that single pulses elicit ATP release from enteric motor neurons that cause a fIJP and a transient relaxation that is difficult to maintain over time; also, NO is released at higher frequencies causing a sustained hyperpolarization and relaxation. These differences might be responsible for complementary mechanisms of relaxation being phasic (ATP) and tonic (NO).

[Clinical study on colonic transmission time and the effect of sini powder on it in functional constipation patients].

OBJECTIVE: To investigate the characteristic of colonic transmission in functional constipation (FC) and the effect of traditional Chinese medicine (TCM) Sini Powder (SP) on it. METHODS: The colonic transmission time (CTT) of 36 patients with FC (the FC group) and 22 healthy subjects (control group) was measured through colonic transmission test, and CTT of entire colon and that of various subsections was calculated with Hinton method and Arhan method respectively. After then, the FC group was treated with SP for 7 days, and CTT was detected again after treatment. RESULTS: Before treatment, body mass index (BMI) was higher, CTT of entire colon, left half colonic section, and sigmoid-rectal section were longer in the FC group than those in the control group (P < 0.05), no statistical difference in CTT of right half colon was found between the two groups (P > 0.05). After FC patients being treated with SP, their CTT of whole colon, left half colonic section and sigmoid-rectal section were significantly shortened (P < 0.05). CONCLUSION: FC patients were characterized by increased BMI and CTT prolonged and unevenly distributed in subsections, especially in the left half colon, sigmoid and rectum; SP could shorten the CTT in FC patients.

Sigmoido-rectal junction reflex: role in the defecation mechanism.

The presence of a sphincter at the rectosigmoid junction (RSJ) is debated. This investigation studies the presence or absence of a sphincter and its possible role in sigmoid colon storage and rectal evacuation. Eighteen healthy volunteers (10 males, 8 females) with a mean age of 36.6 +/- 14.8 years (range 21-53) were studied. The pressure response of the sigmoid colon, RSJ, and rectum to sigmoid and rectal distension, respectively, was determined before and after anesthetizing either the sigmoid colon or the rectum. The RSJ length was evaluated by the station pull-through technique. Sigmoid distension with balloon volumes of up to 80.6 +/- 4.4 ml of H2O effected no sigmoid, RSJ or rectal pressure changes (P > 0.05). At a mean sigmoid distension of 88.6 +/- 4.1 ml of H2O, the sigmoid colon showed a significant pressure increase (P < 0.001), a RSJ pressure decrease (P < 0.05), and insignificant pressure changes in the rectum (P > 0.05); the balloon was dispelled into the rectum. Rectal distension of 94.6 +/- 5.8 ml of H2O produced rectal (P < 0.001) and RSJ (P < 0.05) pressure increases. Distension of the anesthetized sigmoid and rectum did not produce pressure changes in the RSJ (P > 0.05). This study demonstrated a high pressure zone at the RSJ of 3.8 +/- 0.7 cm in length. This suggests that the RSJ might act as a functional sphincter. It opens reflexly upon sigmoid contraction, by a reflex we call "rectosigmoid inhibitory reflex," and closes upon rectal contraction, a reflex we call "rectosigmoid excitatory reflex." The former allows the stored feces in the sigmoid colon to pass to the rectum, and the latter reflex prevents stool reflux to the sigmoid upon rectal contraction.

Protective effect of RibCys following high-dose irradiation of the rectosigmoid.

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.

Epithelial cell proliferation in the sigmoid colon of patients with adenomatous polyps increases during oral calcium supplementation.

To study the effect of oral supplemental calcium on colonic epithelial proliferation, 17 adenomatous polyp patients received 1.5 g Ca2+ as calcium carbonate daily during 12 weeks, while on a calcium constant diet, based on the patients' habitual diet. Seven subsequently continued calcium supplementation for 9 months without dietary restrictions. Epithelial proliferation rate in colonic biopsies, expressed as labelling index (%), was determined with 5-bromodeoxyuridine and immunohistochemistry. Biopsies were taken from the midsigmoid at time of polyp excision and at the end of the intervention period. Median labelling index increased from 6.1% before to 8.7% after 12 weeks calcium (n = 17, P < 0.02). This was due to increased labelling in the basal third of the crypts (11.9 vs 16%), whereas labelling in mid and luminal compartments was not affected. Labelling index remained increased after 1 year calcium supplementation at 8.8%. Crypt length was not affected by calcium. These results are in contrast to those of others, who have shown a decrease of rectal epithelial proliferation during similar doses of calcium. Therefore, the effect of nutritional intervention on colonic epithelial proliferation should be studied in biopsies taken not only from the rectum, but also from more proximal parts of the colon. Caution with respect to large scale intervention studies with calcium in high risk groups is mandatory.

[Effect of phloroglucinol on rectosigmoid motility stimulated by a test meal. Study in patients with irritable bowel syndrome]. / Effet du phloroglucinol sur la réponse motrice du rectosigmoïde à l'alimentation. Etude chez des sujets atteints du syndrome de l'intestin irritable.

Twenty patients (15 women, 5 men, mean age: 46.3 +/- 11.82 years, mean weight: 70.9 +/- 8.83 kg) presenting with a 8.5 +/- 4.7 years' history of irritable bowel syndrome associated predominantly with postprandial abdominal pain were recruited into the study. They underwent, after an enema, a rectosigmoid manometry (4 channels, low compliant infusion pump and catheters) before and after a 1000 kcal standardized meal. At the end of the meal they were administered intravenously phloroglucinol (two 40 mg ampoules) or placebo (two ampoules). Both treatments were strictly similar and the order of administration was randomly assigned Motor activity at the rectum, rectosigmoid, lower sigmoid and sigmoid level was determined using a motor index calculated for each 15 min period. Three preprandial and four postprandial indices were calculated. Both groups were statistically similar for sex ratio, age and history of disease. A slight difference was noted for mean weight: the caloric instake per kg of weight was a little higher in the phloroglucinol group. Mean preprandial indices were comparable in both groups. Variance analysis showed that the increase in postprandial motor indices was statistically less pronounced in the phloroglucinol group than in the placebo group. In the placebo group a clear cut increase in motor activity was assessed, which was not observed in the phloroglucinol group. This variation of motricity, which was observed at every level, was more pronounced for the first two postprandial indices than for the last two ones. These results suggest that phloroglucinol is able to reduce rectosigmoid motor response after a test meal. This could explain its activity in abdominal pain associated with irritable bowel syndrome.

Effect of coffee on distal colon function.

Ninety nine healthy young volunteers (58 men, 34 women, aged 17-27 years) answered a questionnaire concerning their bowel habit with particular reference to the effects of beverages. Twenty nine per cent (63% women) claimed that coffee induced a desire to defecate. The rectosigmoid motor responses to black, unsweetened coffee were then investigated by multiport manometry in 14 healthy-subjects (12 men, two women, eight of whom claimed coffee caused a desire to defecate (responders). Results revealed an increase in motility index within four minutes after ingestion of both regular and decaffeinated coffee (p less than 0.05) in the eight responders, but not in the six non-responders. The increase in rectosigmoid motility induced by coffee lasted at least 30 minutes. There was no increase in the motility index in any subject after a drink of hot water. These results suggest that drinking coffee can stimulate a motor response of the distal colon in some normal people.

Glucagon and the colon.

The effect of glucagon on human colonic myoelectrical activity is described. By means of intraluminal, serosal, and surface electrodes, recordings from all areas of the large bowel have been obtained. Glucagon inhibited both electrical and pressure rhythms in all subjects tested. Evidence is produced to suggest a direct action on colonic smooth muscle. A controlled trial using glucagon during routine barium enema examinations suggests that it may prove to be useful for hypotonic examinations of the colon where painful spasm is present.