Procoagulant activity in gastroenterology.
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Biomedical subjects
Publications and source records attributed to Z Cohen.
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The functional success rate of the ileoanal reservoir procedure for ulcerative colitis is quite high. Despite the few early and late complications described there is now wide-spread acceptance of this procedure in the management of ulcerative colitis. We report a patient who developed an adenocarcinoma in the rectal cuff four years after having a pelvic pouch procedure. This new late complication brings to light several points including the importance of a radical total mucosectomy. The purpose of this paper is to discuss concern as to whether or not this procedure is indicated in colitis patients in whom severe dysplasia is the primary indication for surgery.
We report the light and electron microscopic findings for two lesions from two patients who died of complications of familial adenomatous polyposis. In the first case microscopy of a small (100 to 200 mu), uniformly dark lesion (the commonest type seen in this condition) showed enlarged retinal pigment epithelial cells with an increased number of pigment granules. This is consistent with the term "hypertrophy of the retinal pigment epithelium", currently used to describe these lesions. In the second case we sectioned a larger (1000 to 1500 mu), oval, grey lesion from the posterior pole. The pigment epithelium was normal, but between it and outer retina was an unusual choristoma consisting largely of myelinated axons and astrocytes.
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Ganglioneuroma is an infrequent tumor composed of sympathetic ganglion cells and sheathed neurites. It arises mainly from the large sympathetic chains, most frequently in the posterior mediastinum and retroperitoneum, but rarely may develop from the peripheral sympathetic chains. It is usually benign, and may grow asymptomatically to relatively large size. However, it can cause symptoms due to local expansion and pressure on adjacent structures. It does not seem to have hormonal activity. Some ganglioneuromas contain immature cells or elements of neuroblastoma or pheochromacytoma and can metastasize. The preoperative diagnosis of retroperitoneal tumors has now become more frequent due to the extensive use of imaging modalities, mainly computed axial tomography. Whenever the imaging correlates with the clinical presentation, or there is a reasonable suspicion of a malignancy, operation is indicated. Many retroperitoneal space-occupying lesions are found in asymptomatic patients during attempts to diagnose other diseases. In these cases opinions differ as to therapeutic approach. Many adrenal tumors may be benign adenomas, and several therapeutic protocols have been proposed. The clinician can decide on the basis of clinical presentation and radiographic features whether a conservative approach rather than operation is indicated. Since the majority of retroperitoneal tumors are malignant, histologic diagnosis is essential and in such cases surgical intervention is warranted. A young patient with a retroperitoneal ganglioneuroma is presented.
Although thrombosis is a frequent complication of total parenteral nutrition (TPN), its pathogenesis has received little scientific attention. We have studied, in vitro, the effects of the component solutions of TPN on the induction and modulation of human monocyte procoagulant activity, an initiator of coagulation. Human peripheral blood mononuclear cells were cultured with (a) 200 microliters of dextrose solution (10%, 15%, 20%, 25%, and 50%), (b) 200 microliters of amino acid solution (full, one-half, and one-quarter strength), and (c) 200 microliters of isosmolar 10% lipid emulsion (LE). Cocultures of LE and 20% dextrose, LE and full-strength amino acid solution, and LE and bacterial lipopolysaccharide were also studied. Cells cultured with lipopolysaccharide or medium alone constituted positive and negative controls, respectively. In addition, cocultures of LE and 20% dextrose, LE and full-strength amino acid solution, and LE and lipopolysaccharide were also studied. Cells were incubated for intervals of 12-72 h, washed, frozen, and assayed for monocyte procoagulant activity (MPCA). Milliunits of MPCA were derived from a standard thromboplastin curve. In addition, spontaneous MPCA levels were measured in healthy volunteers (n = 4) and "home" total parenteral nutrition patients (n = 4) before and after a 2-h infusion of 500 ml of LE. Our results show that, in vitro, hypertonic dextrose and full-strength amino acid solutions induce significant levels of MPCA. Induction of MPCA by dextrose was lymphocyte-independent. Although a significant increase in MPCA by full-strength amino acid solution was seen in cultures of isolated monocytes, a lymphocyte requirement was demonstrated for full MPCA. In contrast, LE significantly inhibited the induction of MPCA by 20% dextrose and full-strength amino acid solution. This inhibitory activity was at the monocyte level. Subfractionation of the LE into triglyceride and phospholipid phases showed the inhibitory capacity to reside in the former. In vivo, patients on home total parenteral nutrition expressed higher spontaneous MPCA levels than normal controls. Ten percent lipid emulsion infusion abolished MPCA expression in both groups. These corroborative in vitro and in vivo data suggest a mechanism for the thrombogenicity of total parenteral nutrition solutions and that the inhibitory properties of LE may be of practical advantage in preventing thrombosis.
Thrombosis is a common sequela of total parenteral nutrition. We have recently demonstrated in vitro that hypertonic total parenteral nutrition solutions are potent inducers of a tissue factor monocyte procoagulant activity, the initiating cofactor of the extrinsic clotting cascade. We have further studied, in vitro, the effects of the component solutions of total parenteral nutrition on the induction and modulation of endothelial cell procoagulant activity. Cultured porcine aortic endothelial cells were incubated with (a) 200 microliters of dextrose solution (5%, 10%, 20%, 25%, and 50%), (b) 200 microliters of amino acid solution [full strength (N), one-fourth strength, and one-half strength], and (c) 200 microliters of 10% lipid emulsion. Cocultures of lipid emulsion and 20% dextrose, lipid emulsion and full-strength 10% amino acid solution (N-amino acid), and lipid emulsion and bacterial lipopolysaccharide also were studied. Cells were incubated for intervals of 3-108 h, washed and frozen, harvested, and assayed for endothelial cell procoagulant activity. Units of endothelial cell procoagulant activity were derived from a standard thromboplastin curve. Our results show that amino acid and hypertonic dextrose total parenteral nutrition solutions are able to strongly induce endothelial cell procoagulant activity expression in vitro. In contrast, lipid emulsion significantly inhibited the induction of endothelial cell procoagulant activity by 20% dextrose, N-amino acid, and lipopolysaccharide. These results provide further evidence for the role of the cellular pathways of coagulation in total parenteral nutrition-induced thrombosis. Furthermore, the inhibitory properties of lipid emulsion may be of practical advantage in reducing total parenteral nut induced thrombosis.
In vitro lymphocyte proliferative assays were performed using Lewis (Lew) and Brown Norway (BN) rats, and compared to induction of monocyte/macrophage procoagulant activity (PCA) in a mixed lymphocyte culture and by endotoxin (LPS) (E. Coli 0111:B4). Splenic mononuclear cells from Lew rats had significantly greater mitogen-induced proliferation to concanavalin A (P = .002) and phytohemagglutinin (P = 0.007). The Lew cells also showed greater allogeneically induced proliferation by BN cells in a one-way MLC in comparison to the reciprocal BN proliferative response (P less than 0.04). PCA induction in peripheral blood mononuclear cells (PBM) by allogeneic stimulation in MLC or total content PCA by LPS did not vary significantly between the 2 strains (P greater than 0.5). Induction of PCA by LPS was rapid, with a moderate rise over basal activity at 3 hr and maximal activity at 6 hr. Two-way allogeneic induction of PCA in PBM from BN and Lew rats resulted in PCA elevation by 3 hr, which became maximal at 18 hr. One-way MLC with Lew or BN cells as responders resulted in moderate increases in PCA by 3-6 hr, with equivalent maximal activities recorded at 18 hr. Viable PCA accounted for 26-32% of total content PCA in both Lew and BN rats. Maximal allogeneic PCA induction by MLC was 14-18% of PCA induced by LPS and required a longer incubation for its expression. Our results indicate that in vitro PCA expression by Lew and BN PBM following allogeneic or endotoxin stimulation shows little interstrain variability in comparison to lymphocyte proliferative responses. Thus PCA appears to more closely reflect the observed in vivo responses of these strains to allogeneic challenge.
After colectomy, continent ileal reservoirs are an accepted alternative to conventional ileostomy for patients with ulcerative colitis. To assess the effect of these reservoirs on digestive function, circulating and morphologic gut endocrine responses were measured in patients with a continent ileostomy or with a pelvic pouch and compared to patients with conventional ileostomy, with active ulcerative colitis and healthy controls. Eight subjects were studied in each group. Basal and postprandial plasma gastrin, enteroglucagon, neurotensin, vasoactive intestinal polypeptide, insulin, pancreatic glucagon, and pancreatic polypeptide in both groups with ileal reservoirs were equivalent to controls. Basal plasma motilin and postprandial plasma gastric inhibitory polypeptide were raised in ileal reservoir patients, but similar changes also occurred in ulcerative colitis patients and those with conventional ileostomy. In one half of patients, cell populations of enteroglucagon, peptide YY, and neurotensin were decreased in pouch mucosa that corresponded with the presence of mucosal inflammation. On the other hand, with pouch inflammation vasoactive intestinal polypeptide immunoreactive nerves were increased and a proportion of the fibres were moderately coarsened. Mucosal concentrations of vasoactive intestinal polypeptide did not, however, exceed that of controls. After an ileal reservoir sufficient reserve remains for gut hormone release into the circulation, suggesting compensation for the presence of a reservoir and the absence of a colon; circulating hormone changes do occur but are consequent upon previous ulcerative colitis. Reservoirs may show neuromorphologic alterations that appear to be related to mucosal inflammation.
Strictureplasty may eliminate or decrease the extent of resection required in patients who have obstructing Crohn's disease of the small bowel. The authors performed 36 strictureplasties at 16 operations in 14 patients. Additional bowel resection was carried out in 13 of the 16 procedures. Early complications included wound infection in one patient, upper gastrointestinal bleeding in one and presumed suture-line leak, treated conservatively, in a third patient. At the end of the follow-up period (mean 16.1 months), 10 patients were asymptomatic and 4 had symptomatic recurrences; 2 of these required reoperation. A number of preoperative factors and operative techniques may have contributed to the favourable results.
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Between December 1981 and March, 1987, 188 ileal reservoir and ileoanal anastomosis procedures were performed at the University of Toronto. Anal anastomotic complications occurred in 24 (12.8%) patients. There were 19 patients who developed a leak as a result of non-healing of the ileoanal anastomosis (group 1). Late fistulae occurred in 5 patients (group 2). Various treatments were employed. In group 1, 2 of 15 (13%) patients treated with drainage and antibiotics, 3 of 7 (43%) in whom the anastomosis was resutured, and 5 of 7 (71%) in whom repair was performed by advancing the ileal outlet and resuturing the anastomosis, healed their anastomosis. One patient was treated successfully by performing a fistulotomy. Treatment was unsuccessful in one patient in whom the ileal reservoir and ileoanal anastomosis were revised and re-anastomosed. One patient (50%) in group 2 was treated successfully by advancing the ileal outlet and resuturing the anastomosis. Complete healing of the anastomosis was achieved in 12 patients (50%), although 3 patients subsequently required excision of the reservoir because of inability to evacuate spontaneously (1), incontinence (1), or psychological reasons (1). All nine (38%) patients who were functioning with their ileal reservoir were continent. One patient intubated the reservoir. The rate of urgency and soiling, and the number of bowel movements per 24 hours did not differ significantly from those of patients without these anastomotic complications. Our results suggest that early diagnosis and repair of ileoanal anastomotic dehiscence by advancement of the ileal outlet and resuturing of the ileoanal anastomosis results in improved reservoir salvage and satisfactory functional results.
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A retrospective review was undertaken to determine factors important in predicting functional results following the ileal reservoir and ileoanal anastomosis procedure. One hundred seventy-nine patients underwent ileal reservoir and ileoanal anastomosis at the University of Toronto between December 1981 and January 1987. One hundred sixty-three patients had ulcerative colitis, 11 had familial adenomatous polyposis, and five had Crohn's disease. A J-reservoir was constructed in 72 patients and an S-reservoir in 107 patients. Functional results were assessed in 102 patients who had their loop ileostomies closed for more than one year. The most significant technical complications were anal anastomotic leaks (10 percent), reservoir anastomotic leaks (3.9 percent), anal anastomotic stricture (7.8 percent), late fistula-inano (2.8 percent), small-bowel obstruction (19 percent), and loop ileostomy complications (23 percent). Overweight males and patients with operative blood loss greater than 1000 cc developed anal stricture more frequently (P less than .005). Patients who had a stapled J-reservoir had a higher rate of reservoir leak. The average number of bowel movements reported by patients for 24 hours was 6.2 +/- 3.1. Only ten (9.8 percent) patients had to intubate their reservoir to empty it. Urgency was experienced by 24 patients and soilage at night by 23 (22.5 percent) and during the day by 18 (17.6 percent). Seven patients (6.8 percent) were incontinent during the night and only one during the day. Pouchitis was reported in 16 patients (15.7 percent). Patients with anal anastomotic stricture had more urgency and pouchitis, and had to intubate their reservoir more frequently (P less than .05). No other factors analyzed affected technical or functional results.
Fifty patients were assessed for congenital hypertrophy of the retinal pigment epithelium (CHRPE) as a potential phenotypic marker for familial adenomatous polyposis (FAP), with and without other extracolonic manifestations (ECM). The ocular anomaly, which characteristically is multiple, benign, and congenital, was studied in three groups. Group 1 contained eight patients with nonpolyposis colon cancer as disease controls. All had negative eye findings. Group 2 included 40 patients with FAP, 35 (87.5 percent) of whom had retinal lesions. Twenty-two of 25 patients with FAP alone had retinal lesions while 13 of 15 patients with FAP and extracolonic manifestations were similarly affected. Group 3 included 11 offspring at risk for FAP. Eight (72.7 percent) offspring had retinal lesions. One of the eight subjects with the ocular trait was subsequently diagnosed with FAP. Two of the eight patients also had other ECM but have not been sigmoidoscoped for FAP. Seven of 11 offspring (mean age, 12.5 years) have had negative flexible sigmoidoscopy. Specificity of the retinal lesions in FAP cannot be ascertained until subsequent adenomas are identified on follow-up of the group at risk. The gene responsible for CHRPE appears to be transmitted from one generation to another, demonstrated by the high sensitivity of the retinal lesions in patients with FAP alone and with other ECM.