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At least 811 records · Page 45Linked to original sources
PubMed1989

Ro 03-8799: preferential relative uptake in human tumor xenografts compared to a murine tumor: comparison with SR-2508.

The pharmacokinetics of Ro 03-8799 and SR-2508 were studied in 6 tumor cell lines (5 human, 1 murine) transplanted into athymic nude mice. The human tumors were rectocolic adenocarcinomas (HRT18, HT29) and melanomas (Be11, Na11+, Na11-), the rodent tumor was a mammary tumor (EMT6). The concentrations of drugs in tumor, blood, plasma, and red cells were measured by HPLC 15, 30, and 45 minutes after the simultaneous i.v. injection of 0.1 mg/g of each compound. Little or no difference was found between the concentrations in the plasma, blood, and red cells for either drug; SR-2508 concentration was higher than that of Ro 03-8799. Both compounds were concentrated in all the tumors, the concentration increases or decreases as a function of the time, depending on the cell line; there was more Ro 03-8799 in the pigmented melanomas than in the other tumors. The relative uptake of Ro 03-8799 and SR-2508 in the tumor was evaluated by the ratio of drug concentrations in the tumor and in the blood. The results suggest that Ro 03-8799 and SR-2508 accumulated in all the tumors, the relative uptake of Ro 03-8799 was higher than that of SR-2508. For human tumors, the ratios increased between 15 and 45 minutes. They ranged from 1.2 to 3.6 for SR-2508 and from 3.1 to 14.6 for Ro 03-8799. For Ro 03-8799, the highest ratios were found for the melanomas; the uptake was higher in the pigmented Na11+ tumors than in the non-pigmented Na11-. The ratios for EMT6 were about 2.3 for SR-2508 and 4.7 for Ro 03-8799; these ratios varied slightly between 15 and 45 minutes.

Animals↗
PubMed2005

[Desmoid tumor in a male breast in the context of Gardner's syndrome. Case report].

Fibromatosis (Desmoid tumor) of the male breast is an exceptional location. We present a case of such a tumor, in the context of Gardner's syndrome. A palpable mass was discovered in the right breast of a 52 years old man, with a history of rectocolic adenomatous polyposis. Mammography ant thoracic CT scan showed a stellar tumor, mimicking a breast cancer. Treatment consisted of wide excision and histology revealed a desmoid tumor. Desmoid tumors of the breast are benign lesions; they should be widely excised because of a high risk of recurrence. Coloscopy is indicated in the presence of mammary fibromatosis, to look for associated multiple polyps, confirming the diagnosis of Gardner's syndrome.

Breast Neoplasms, Male↗
PubMed2004

Mediation of annexin 1 secretion by a probenecid-sensitive ABC-transporter in rat inflamed mucosa.

Annexin 1 is secreted by mammalian cells but lacks a leader signal sequence necessary to lead it to the classical secretory pathway via the endoplasmic reticulum. The mechanisms involved in the secretion of leaderless proteins remain uncertain. It has been suggested to involve membrane translocation via an ABC-transporter (ATP binding cassette). Using cultured inflamed mucosa from rectocolitis induced in rats, we studied if annexin 1 secretion followed the two main characteristics of ABC-transporter substrates: dependency on ATP hydrolysis and competitive inhibition by several other ABC-transporter substrates. Annexin 1 secretion is inhibited in a dose-dependent manner by two ATPase inhibitors. The inhibition reached 63.2+/-3.2%, 66.1+/-3.73% and 88.6+/-1.4% in the presence of 2mM vanadate, 0.5 and 1mM pervanadate, respectively. The efflux of calcein, a known ABC-transporter substrate, is similarly inhibited by 69.4+/-2.8% in the presence of 1mM pervanadate. Probenecid, an inhibitor of several ABC-transporters of the subfamilly ABCC or MRP (multidrug resistant associated protein), also inhibited annexin 1 secretion in a dose-dependent manner. As compared to control, 10mM probenecid reduced annexin 1 secretion by 72+/-20% and 20mM by 95.0+/-9%. By contrast, annexin 1 secretion is not blocked by other inhibitors of MRP1 (indomethacin, MK571), MRP2 (ochratoxin A1 or MK571), MRP5 (trequinsin or sulfinpyrazone) or by verapamil, cyclosporin A or glyburide. Taken together, our results show that annexin 1 secretion appears to share the efflux properties of ABC-transporter substrates.

ATP-Binding Cassette Transporters↗
PubMed1998

All mechanical low rectal anastomosis in children.

PURPOSE: The aim of this study is to demonstrate the feasibility and usefulness of mechanical suturing in children for low rectal anastomosis. METHODS: The study group includes 31 children operated on from January 1993 to July 1996 by the same senior surgeon, performing the modified Duhamel procedure for Hirschsprung's disease in 17 children, intestinal neuronal dysplasia in seven, and the Knight-Griffen procedure in seven pediatric patients with chronic ulcerative colitis. RESULTS: In all the cases the technique of "viscero-synthesis" was performed using the mechanical stapler. A circular stapler has been used for the end-to-end and the end-to-side anastomosis between the anal canal or the back wall of the rectum with the pulled viscus, while a linear endoscopic stapler (GIA) has been used for the consolidation of the rectocolic wall in the modified Duhamel technique. CONCLUSIONS: The results obtained demonstrate that the mechanical staplers in children are safe and effective in low rectal anastomosis, sparing operative time and reducing the risk of anastomotic dehiscence; however, the size of circular instruments limits its use in neonates and small infants.

Adolescent↗
PubMed1992

[Acute respiratory insufficiency caused by diffuse pulmonary hemorrhage].

Two cases of adult respiratory distress syndrome due to diffuse pulmonary haemorrhage are reported. The first patient was treated with azathioprine, prednisolone, cyclosporine and ranitidine for haemorrhagic rectocolitis; the second has untreated primary biliary cirrhosis. Haemoptysis only occurred in the latter. Both had severe isolated hypoxaemia. Chest X-rays revealed bilateral alveolar infiltrates. Bronchoscopies showed a diffusely bleeding bronchial tree. Both patients recovered after having been mechanically ventilated with positive end-expiratory pressure for six and eight days respectively. The cause of the diffuse pulmonary haemorrhage was, in the first case, severe thrombocytopaenia (17,000 G.1-1) of central origin, and, in the other patient, an unspecified vasculitis. Diffuse pulmonary haemorrhage should be added to the list of possible causes of the adult respiratory distress syndrome.

Adult↗
PubMed2004

[Renal amyloidosis complicating the outcome of chronic inflammatory colitis].

INTRODUCTION: In 4 patients we observed the association of an amyloid nephropathy and a chronic inflammatory bowel disease (Crohn's' disease in 3 cases and ulcerative rectocolitis in 1 case). OBSERVATIONS: These patients, aged a mean of 37 years (range: 28-48 years), had been admitted for exploration of a nephrotic syndrome associated with renal failure in 2 cases. The investigations lead to the diagnosis of AA type amyloidosis in the 4 cases. One patient was lost from follow-up. One patient was treated with salazopyrine, one with corticosteroids and one with colchicine. After a mean follow-up of 16 months (5-30 months), all the patients had persistent nephrotic syndrome, with end stage renal failure in one case, persistence of normal renal function in one case and improved renal function in one case. None of the patients exhibited remission in the nephrotic syndrome. The response of amyloidosis to the treatment of the chronic inflammatory bowel disease varied. Corticosteroids and colchicine stabilised renal function in 2 of our patients but without remission in the nephrotic syndrome. DISCUSSION: AA amyloidosis is a rare complication of inflammatory bowel disease. The indication for colchicine is important to consider particularly since the response of amyloidosis to the treatment of the causal disease does not, in the majority of cases, lead to the remission of the amyloidosis, the prognosis of which is determined by the extent of renal involvement.

Adrenal Cortex Hormones↗
PubMedDate not supplied

Kaposi's sarcoma confined to the colorectum: a case report.

Reported is a new case of a Kaposi's sarcoma involving only the colorectal area in an HIV-negative patient presenting with hemorrhagic rectocolitis. The colonoscopic examination and the radiological imaging showed the presence of multiple nodular pseudopolypoid formations in the rectum, which suggested, in the differential diagnosis, primarily a malignant non-Hodgkin lymphoma.

Adult↗
PubMed1989

A case of diversion rectitis.

We report a case of diversion rectocolitis, an inflammatory process that frequently develops in the distal blind colorectum, after surgical diversion of the fecal stream. Since the endoscopic and histologic findings closely resemble those of inflammatory bowel disease, the differential diagnosis can be difficult. However, the inflammation permanently resolves after surgical reanastomosis. Because diversion colitis can also be treated effectively by local application of short-chain fatty acids, it has been postulated that a local nutritional deficiency, resulting from the absence of these acids, triggers the inflammation.

Aged↗
PubMed2005

Shigella sonnei meningitis due to interleukin-1 receptor-associated kinase-4 deficiency: first association with a primary immune deficiency.

BACKGROUND: Inherited interleukin-1-receptor-associated kinase-4 (IRAK-4) deficiency is a recently described immunodeficiency associated with pyogenic bacterial infections and a poor inflammatory response. Shigella sonnei is generally associated with outbreaks of rectocolitis in developed countries, but systemic illnesses have occasionally been reported. An underlying primary immunodeficiency has not been found in such cases before now. METHODS: We report the clinical and immunological features of a patient with IRAK-4 deficiency who has a history of systemic shigellosis in addition to other infections. RESULTS: The patient has a history of Staphylococcus aureus, Streptococcus pneumoniae, and Pseudomonas aeruginosa infections during childhood and an episode of S. sonnei septicemia and meningitis at 10 years of age. This patient's history contrasted with that of other individuals infected concurrently by the same organism. Of note, these episodes were not accompanied by acute phase responses in our patient. Subsequently, the patient has had more episodes of staphylococcal disease, but no systemic illnesses. The patient is now 30 years old and has been doing well since prophylactic antibiotic treatment was stopped 4 years ago. DISCUSSION: To our knowledge, this is the first report of a case of systemic shigellosis in a person with a primary immunodeficiency, expanding the spectrum of infections associated with IRAK-4 deficiency. Thus, immunity mediated by IRAK-4 seems to be crucial for both the containment of and the inflammatory response to S. sonnei infection in the intestinal mucosa. IRAK-4 deficiency and related disorders should be considered in patients with systemic shigellosis.

Anti-Bacterial Agents↗
PubMed2005

Mucosal lymphoid infiltrate dominates colonic pathological changes in murine experimental shigellosis.

BACKGROUND: Shigella species are invasive human pathogens that cause acute rectocolitis by triggering a dysregulated inflammatory reaction in the colonic and rectal mucosa. Because mice are naturally resistant to shigellosis, there is no mouse model that mimics human disease. We explore the susceptibility of intestinal flora-depleted mice to shigellosis after intragastric infection with Shigella strains. METHODS: Mice given 5 g/L streptomycin as a beverage were infected intragastrically with 1 x 108 cfu of either invasive or noninvasive Shigella strains. RESULTS: We found that invasive Shigella strains persist up to 30 days in feces, whereas the persistence of noninvasive Shigella strains was reduced. Colonization primarily involves the colon and the cecum and, to a lesser extent, the ileum. The hallmark of inflammation in the intestinal tissue is a dramatic expansion of the lymphoid follicles, in which a high apoptotic index is recorded. CONCLUSIONS: We provide a murine model in which shigellae are able to reach their natural tissue target: the colon. Moreover, the absence of polymorphonuclear leukocyte recruitment and of epithelial cell lesions reveal some aspects of shigellosis that are usually hidden by the prevalence of this cell population. This novel model may contribute to the identification of new targets for vaccines and therapies.

Animals↗
PubMed1995

Chronic diarrhea among adults in Kigali, Rwanda: association with bacterial enteropathogens, rectocolonic inflammation, and human immunodeficiency virus infection.

One hundred patients with chronic diarrhea were seen in the Department of Internal Medicine at the Centre Hospitalier de Kigali, Rwanda; stool and/or rectal swab culture was performed for these patients, and they underwent rectoscopy and serological testing for human immunodeficiency virus type 1 (HIV-1). Enteropathogenic bacteria were isolated from 39 (39%) of the patients: Shigella species (22 of 100 patients tested), non-typhi Salmonella (11/100), Aeromonas species (5/60), and Campylobacter species (4/60). Rectocolitis was seen in 70 (70%) of the patients. HIV-1 antibodies were detected in 82 (94%) of 87 patients tested. Cytomegalovirus was not found in rectal biopsy specimens from 29 patients. Entamoeba histolytica was detected in two of 31 rectal smears. Idiopathic ulcerative colitis was diagnosed for two HIV-1-seropositive patients. One or more AIDS-defining diseases were found in 32 (32%) of the patients, and 72 (72%) fulfilled the World Health Organization's clinical case definition criteria for AIDS. Chronic diarrhea, as seen in a hospital setting in a region highly endemic for HIV-1 infection, is strongly associated with HIV-1 infection, with rectocolonic inflammation, and with infection due to enteropathogenic bacteria.

Adult↗
PubMed1999

Salivary gland involvement in patients with chronic pancreatitis.

The salivary glands are structurally similar to the exocrine pancreas and may be involved in the course of diseases of autoimmune origin (sclerosing cholangitis, ulcerative rectocolitis, primary biliary cirrhosis). For a not-yet-quantified proportion of chronic pancreatitis (CP) cases, a possible autoimmune pathogenesis has been postulated. The aim of the study was to assess the frequency of salivary ductal system abnormalities in patients with CP. Fifty-one patients with CP consecutively admitted to our center were studied (44 men, seven women; mean age, 48.2 +/- 10.8 years). The mean duration of disease was 11.7 years (range, 1-37 years); 44 (86%) of 51 patients had pancreatic calcifications, 25 (49%) of 51 diabetes, 25 (52%) of 48 steatorrhea, and 32 (63%) of 51 underwent pancreatic surgery. As a control group, we studied 10 patients of whom four with liver cirrhosis (three alcoholic and one posthepatitis; three men, one woman; mean age, 57 +/- 12.5 years), and six with temporomandibular pain (five men and one woman; mean age, 42 +/- 10.3 years). The patients were given parotid sialography, the findings being read by two independent observers. In two CP patients, parotid sialography was unsuccessful. Fifteen (31 %) of 49 patients and none of the 10 control patients exhibited abnormalities of the glandular ducts compatible with chronic inflammation of the salivary ducts (p = 0.039). None of the CP patients had salivary intraductal calcifications. Findings of parotid ductal abnormalities are frequent in the course of CP and may indicate a common pathogenetic mechanism, even of an immune type.

Adult↗
PubMed1994

Influence of 5-HT3 receptor antagonists in visceromotor and nociceptive responses to rectal distension before and during experimental colitis in rats.

We investigated the possible involvement of 5-HT3 receptors in the colonic motor alterations and abdominal pain evoked by rectal distension (RD) in rats, under normal and inflammatory conditions. Responses to RD were evaluated by electromyography in rats treated with 5-HT3 antagonists (ondansetron and cilansetron, 0.1 and 1 mg/kg, intraperitoneally), before and 3 days after intrarectal administration of TNB/ethanol. RD evoked a significant (P < 0.05) and gradual inhibition of the occurrence of colonic spike bursts (SB) and a gradual increase in abdominal SB from 11 mm in diameter on wards. Ondansetron and cilansetron (0.1 mg/kg) significantly reduced both the colonic (62 and 66%, respectively) and the abdominal response (28 and 61%, respectively) for an 11 mm diameter of RD. After TNB/ethanol, both colonic and abdominal responses to RD were significantly (P < 0.05) enhanced and appeared for a lower diameter (9 mm) (colon: 4.8 +/- 0.9 vs 8.4 +/- 1.1, abdomen: 7.7 +/- 1.5 vs 0.5 +/- 0.4). Cilansetron (0.1, 1 mg/kg) significantly (P < 0.05) attenuated the TNB-induced colonic motor inhibition, while ondansetron and cilansetron (0.1, 1 mg/kg) reduced the TNB-induced increase in abdominal response. We conclude that 5-HT and 5-HT3 receptors mediate RD-induced viscerosensitive alterations in rats, both in normal conditions and during TNB-induced rectocolitis. However, the relative efficacy of the 5-HT3 receptor antagonists depends on the experimental conditions (intact or inflamed bowel) and does not appear to increase with the dose.

Abdominal Pain↗
PubMed1998

Influence of trimebutine on inflammation- and stress-induced hyperalgesia to rectal distension in rats.

The effects of trimebutine and its major metabolite, N-desmethyltrimebutine on inflammation- and stress-induced rectal hyperalgesia have been evaluated in rats fitted with electrodes implanted in the longitudinal striated muscle of the abdomen. Intermittent rectal distension was performed before and 3 days after induction of rectal inflammation by local infusion of trinitrobenzenesulphonic acid (in ethanol). Stress consisted of 2h partial restraint and rectal distension was performed before and 30min after the end of the partial restraint session. The animals were treated intraperitoneally with trimebutine or desmethyltrimebutine (5, 10 or 20mgkg(-1)) or vehicle 15min before rectal distension. Naloxone (1mgkg(-1)) or saline was injected subcutaneously before trimebutine and desmethyltrimebutine. Before treatment trimebutine at the highest dose (20mgkg(-1)) reduced the abdominal response to rectal distension for the highest volume of distension (1.6mL) whereas desmethyltrimebutine was inactive. After rectocolitis the abdominal response to rectal distension was enhanced and trimebutine at 5mgkg(-1) reduced and at 10 mgkg(-1) suppressed inflammation-induced hyperalgesia, an effect reversed by naloxone. Desmethyltrimebutine was inactive. Stress-induced hypersensitivity was attenuated or suppressed, or both, by trimebutine and desmethyltrimebutine at doses of 5, 10 or 20mgkg(-l); greater efficacy was observed for desmethyltrimebutine and the effects were not reversed by naloxone. It was concluded that trimebutine and desmethyltrimebutine are active against inflammation- and stress-induced rectal hyperalgesia but act differently. The effect of trimebutine on inflammation-induced hyperalgesia is mediated through opioid receptors.

Animals↗
PubMed2006

The bacterial weaponry: lessons from Shigella.

Shigella, a Gram-negative bacterial species of the family Enterobacteriaceae, causes bacillary dysentery in humans, an acute rectocolitis that reflects the capacity of the microorganism to disrupt, invade, and cause the inflammatory destruction of the intestinal epithelium. Here, the pathogenesis of Shigella infection is analyzed in the context of the disruption of the homeostatic balance that protects the gut against inflammation in the presence of its commensal flora. Thus a unified view by which enteroinvasive pathogens allow identification of key signalling molecules and pathways involved in the regulation of intestinal inflammation, thereby providing keys to understand inflammatory bowel diseases (IBDs) such as Crohn's disease and ulcerative colitis.

Dysentery, Bacillary↗
PubMed1977

Radiology of invasive amebiasis of the colon.

Entamoeba histolytica is a protozoan that is endemic in various parts of the world, including some areas of the United States. It may live in the large bowel in its cyst form without harming the host (commensalism) or, for as yet poorly understood reasons, invade the tissues as a trophozoite producing invasive amebiasis of the colon. In a review of over 3,000 cases of invasive amebiasis, the clinico-pathologic forms of the disease were: ulcerative rectocolitis (95%), typhloappendicitis (3%), ameboma (1.5%), and fulminating colitis and toxic megacolon (0.5%). Different radiographic patterns are seen in each clinical form with varying degrees of specificity. It is vitally important that this disease be included in the differential diagnosis of large bowel pathology even in nonendemic areas. Several referral patients who have received inappropriate therapy for inflammatory bowel disease with near disastrous results are seen at one of our institutions (Loyola) each year.

Colitis↗
PubMed1992

Hidden damage revealed.

Nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal lesions should be suspected when a patient receiving NSAID therapy has pain or signs of hemorrhage that are severe enough to warrant an emergency endoscopy. However, with endoscopy, patients receiving NSAID therapy with no particular gastrointestinal symptoms may also be found to have lesions. These lesions are polymorphic in character and lack clear anatomic and clinical parallels with spontaneous lesions. Endoscopically, they are of three types: (1) Advanced focal or diffuse lesions, uncommon and not usually seen in ambulatory patients; (2) large or diffuse, ulcerated or hemorrhagic lesions, that can be differentiated from those seen in typical digestive system pathology; and (3) microlesions, often responsible for false-negative examinations and now detectable through advances in electronic endoscopy. Lower bowel or ileocolonic damage is also a common finding but has only recently come to clinical attention. The endoscopic appearance of these intestinal lesions suggests a superficial inflammatory bowel disease such as hemorrhagic rectocolitis or Crohn's disease.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2004

IL-8 is a key chemokine regulating neutrophil recruitment in a new mouse model of Shigella-induced colitis.

The lack of a mouse model of acute rectocolitis mimicking human bacillary dysentery in the presence of invasive Shigella is a major handicap to study the pathogenesis of the disease and to develop a Shigella vaccine. The inability of the mouse intestinal mucosa to elicit an inflammatory infiltrate composed primarily of polymorphonuclear leukocytes (PMN) may be due to a defect in epithelial invasion, in the sensing of invading bacteria, or in the effector mechanisms that recruit the PMN infiltrate. We demonstrate that the BALB/cJ mouse colonic epithelium not only can be invaded by Shigella, but also elicits an inflammatory infiltrate that, however, lacks PMN. This observation points to a major defect of mice in effector mechanisms, particularly the lack of expression of the CXC chemokine, IL-8. Indeed, this work demonstrates that the delivery of recombinant human IL-8, together with Shigella infection of the colonic epithelial surface, causes an acute colitis characterized by a strong PMN infiltrate that, by all criteria, including transcription profiles of key mediators of the innate/inflammatory response and histopathological lesions, mimics bacillary dysentery. This is a major step forward in the development of a murine model of bacillary dysentery.

Animals↗