Asunto(s)
Neoplasias Colorrectales/prevención & control , Tamizaje Masivo/normas , Pólipos del Colon , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales Hereditarias sin Poliposis , Humanos , Enfermedades Inflamatorias del Intestino , Factores de RiesgoRESUMEN
We have investigated the role of the colonic nervous system in regulating the release of peptide YY (PYY) from the isolated perfused rabbit distal colon. In addition, we have studied the role of cAMP- and Ca(2+)-dependent mechanisms in mediating the release of PYY. We investigated three agents which stimulate increases in intracellular cAMP (vasoactive intestinal polypeptide (VIP), cholera toxin, and forskolin) and three agents which raise intracellular Ca2+ concentrations (substance P, carbachol, and the calcium ionophore A23187). The three cAMP-dependent agents, VIP (10(-7) M and 3 x 10(-7) M), cholera toxin (100 micrograms), and forskolin (10(-6) M and 10(-5) M) significantly stimulated release of PYY (P < 0.05). Tetrodotoxin (3 x 10(-6) M) did not alter forskolin (10(-5) M) stimulated release of PYY. Substance P (10(-9) M and 10(-8) M), carbachol (10(-5) M), and A23187 (10(-6) M) failed to stimulate the release of PYY. These results suggest that the colonic neurotransmitter VIP participates in the modulation of PYY release from rabbit distal colons. Further, these studies suggest that release of PYY is mediated by cAMP-dependent pathways.
Asunto(s)
Colon/efectos de los fármacos , Colon/metabolismo , AMP Cíclico/fisiología , Péptidos/metabolismo , Acetilcolina/farmacología , Adenilil Ciclasas/efectos de los fármacos , Adenilil Ciclasas/fisiología , Animales , Calcimicina/farmacología , Carbacol/farmacología , Toxina del Cólera/farmacología , Colforsina/farmacología , Colon/enzimología , Técnicas In Vitro , Sistema Nervioso/efectos de los fármacos , Fenómenos Fisiológicos del Sistema Nervioso , Péptido YY , Perfusión , Conejos , Estimulación Química , Sustancia P/farmacología , Tetrodotoxina/farmacología , Péptido Intestinal Vasoactivo/farmacologíaRESUMEN
The aims of this study were to calculate the true incidence of colonic carcinoids in Connecticut from 1976 to 1986 and to determine the outcome of patients with these lesions. Fifty-four patients with carcinoids of the colon were identified (23 male and 31 female patients). Their average age was 64.1 +/- 2.1 years, with a range of 12 to 83 years. The age-adjusted incidence was 0.31 cases/100,000 population/year. Forty-eight percent of the carcinoids were located in the cecum; 16%, ascending colon; 6%, transverse colon; 11%, descending colon; 13%, sigmoid colon; and 6%, not assigned. Follow-up information was available in all cases. The crude 2-year survival rate was 63%, whereas the 5-year survival rate was 37%. Only one of six (16.6%) lesions that were 2 cm or smaller metastasized, whereas 23 of 31 lesions larger than 2 cm metastasized (74%). Six patients have survived an average of 43.5 months after local excision of their carcinoids. Fourteen patients died of their carcinoids. Metachronous gastrointestinal malignant neoplasms developed in six patients. These results suggest that, when found at an early stage, carcinoids of the colon (2 cm or smaller) can be treated by local excision. The vast majority of colonic carcinoids, however, are discovered at an advanced stage and should be treated aggressively with standard colonic resection. In addition, surveillance of the entire gastrointestinal tract should be initiated in these patients because of a high rate of other gastrointestinal malignant neoplasms.
Asunto(s)
Tumor Carcinoide/epidemiología , Neoplasias del Colon/epidemiología , Sistema de Registros , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Tumor Carcinoide/mortalidad , Tumor Carcinoide/patología , Tumor Carcinoide/terapia , Neoplasias del Colon/mortalidad , Neoplasias del Colon/patología , Neoplasias del Colon/terapia , Connecticut/epidemiología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Análisis de SupervivenciaRESUMEN
Short-chain fatty acids (SCFAs) form the major ionic fraction of stool, provide the major metabolic substrate for colonic epithelium, and promote mucosal ion transport. Despite this prominent role of SCFAs in metabolism of the colon, their effect on colonic endocrine cell function has not been studied. Consequently, we hypothesized that SCFAs might modulate release of peptide YY (PYY) from colonic type-L endocrine cells. The specific aims of this study were to measure release of PYY from the isolated perfused rabbit distal colon stimulated by intraluminal infusion of 0.9% saline, acetate (10 mM), acetoacetate (10 mM), n-butyrate (1, 3.3, 10, 100 mM), and pyruvate (10 mM). PYY levels were measured by radioimmunoassay in the venous effluent of the rabbit colon. All four SCFAs (10 mM) caused at least a twofold increase in integrated release of PYY from the isolated perfused rabbit colon. Graded concentrations of n-butyrate caused a stepwise release of PYY. This study suggests that SCFAs may modulate the release of colonic PYY in rabbits.
Asunto(s)
Colon/efectos de los fármacos , Ácidos Grasos/farmacología , Péptidos/metabolismo , Acetatos/farmacología , Acetoacetatos/farmacología , Animales , Butiratos/farmacología , Colon/metabolismo , Péptidos Similares al Glucagón/farmacología , Técnicas In Vitro , Péptido YY , Péptidos/análisis , Perfusión , Piruvatos/farmacología , Conejos , RadioinmunoensayoRESUMEN
Acute acalculous cholecystitis (AAC) is a disease that causes high rates of morbidity such as those traditionally observed in the critically ill. Recently we noted an increase in the de novo presentation of outpatients with this disease. Our aim was to characterize this disease in outpatients, identify risk factors, and assess clinical outcome. Therefore a 7-year review of the Yale experience with AAC was undertaken. Forty-seven patients were identified. Seventy-seven per cent (36 of 47 patients) developed AAC at home without evidence of acute illness or trauma, while 23% (11 of 47 patients) developed the disease while hospitalized. Significant vascular disease was observed in 72% of outpatients. A 38% morbidity rate and 6% mortality rate were observed. We conclude that AAC occurs commonly in elderly male outpatients with vascular disease and that these patients incur significant morbidity in association with this condition. AAC should be suspected and prompt surgical management instituted when these patients present with an acute right upper quadrant inflammatory process.
Asunto(s)
Colecistitis/epidemiología , Enfermedad Aguda , Anciano , Anciano de 80 o más Años , Colelitiasis , Connecticut/epidemiología , Femenino , Humanos , Masculino , Morbilidad , Pacientes Ambulatorios , Prevalencia , Factores de RiesgoRESUMEN
Acute acalculous cholecystitis is a virulent disease of uncertain etiology observed most commonly in critically ill patients. Although the precise mechanism is unknown, the most commonly postulated theories regarding its pathogenesis are bile stasis, sepsis, and ischemia. The role of ischemia in this process, whose etiology is multifactorial, has been difficult to elucidate. Consequently, we report two patients who developed acute acalculous cholecystitis without apparent risk for the disease other than severe visceral atherosclerosis. Both patients had symptomatic mesenteric vascular disease requiring revascularization and developed fulminant acalculous cholecystitis temporally related to exacerbation of their visceral ischemia. These cases suggest that patients with visceral atherosclerosis may be at increased risk for acute acalculous cholecystitis, perhaps due to impaired mucosal resistance when other factors, such as bile statis and sepsis, are also present.
Asunto(s)
Arteriosclerosis/complicaciones , Colecistitis/etiología , Isquemia/complicaciones , Oclusión Vascular Mesentérica/complicaciones , Enfermedad Aguda , Adulto , Femenino , Vesícula Biliar/irrigación sanguínea , Humanos , Masculino , Arterias Mesentéricas/fisiopatología , Persona de Mediana EdadRESUMEN
The relationship between gastrointestinal neoplasms and Crohn's disease is poorly defined. The purpose of this study was to characterize the features of gastrointestinal malignancies that developed in Crohn's patients. In this retrospective review the authors identified six patients with Crohn's disease who developed such lesions over a 20-year period: four patients had colorectal cancers and two had ileal malignant neoplasms. Patients averaged 52.7 years of age (range, 21 to 61 years). Three patients were men and three women. Five of the six patients had endured Crohn's disease for more than 20 years. Only two lesions were diagnosed before surgery. The colorectal lesions were predominantly right-sided and all occurred in bowel segments with active Crohn's disease. The lesions demonstrated aggressive histologic features: three of six tumors were poorly differentiated, one of the five adenocarcinomas was mucinous, and three of the colorectal cancers were Dukes' B or C lesions. Four of six patients survived five or more years. There was a single malignant carcinoid, which represents the seventh case report of a carcinoid tumor occurring in a patient with Crohn's disease. This study indicates that patients with Crohn's disease develop a wide variety of small bowel and colorectal cancers. Furthermore, it suggests that Crohn's patients with colonic disease should periodically undergo surveillance colonoscopy.
Asunto(s)
Neoplasias Colorrectales/complicaciones , Enfermedad de Crohn/complicaciones , Neoplasias del Íleon/complicaciones , Adenocarcinoma/complicaciones , Adenocarcinoma/epidemiología , Adulto , Tumor Carcinoide/complicaciones , Tumor Carcinoide/epidemiología , Neoplasias Colorrectales/epidemiología , Connecticut/epidemiología , Femenino , Humanos , Neoplasias del Íleon/epidemiología , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de TiempoRESUMEN
The purpose of this study was 1) to measure the effect of graded concentrations of oleic acid and deoxycholic acid (DCA) on the release of peptide YY (PYY) and enteroglucagon and 2) to test whether DCA-stimulated release of PYY was neurally mediated by blocking neuronal conduction with tetrodotoxin. Studies were performed in isolated left colons from New Zealand White rabbits. Oleic acid in concentrations from 0.22 to 22 mM suspended in 10 mM DCA significantly stimulated release of PYY (P less than 0.01) but resulted in no graded response (Bartlett's test, P = 0.15). Similarly, oleic acid (2.2 mM) suspended with ursodeoxycholic acid (10 mM) produced no increased release of PYY above that achieved by ursodeoxycholic acid alone. In contrast, oleic acid (2.2 and 22 mM suspended with 10 mM DCA) produced a graded release of enteroglucagon during the stimulated period. Deoxycholic acid caused a concentration-dependent release of PYY (1, 3.3, 10, and 25 mM) during the stimulated period. Deoxycholic acid (1 and 10 mM) did not significantly increase enteroglucagon release. Tetrodotoxin blockade had no effect on release of PYY stimulated by 10 mM DCA. Because PYY and enteroglucagon are both found in colonic endocrine cells, these results suggest that the release of PYY and enteroglucagon are mediated by specific secretagogues and not simply caused by noxious effects of the agonists. Also, this study has demonstrated that DCA-stimulated release of PYY is not dependent on neuronally mediated mechanisms.
Asunto(s)
Colon/metabolismo , Ácido Desoxicólico/farmacología , Péptidos/metabolismo , Animales , Cromatografía Liquida/métodos , Colon/patología , Colon/ultraestructura , Hormonas Gastrointestinales/metabolismo , Técnicas In Vitro , Microscopía Electrónica , Ácido Oléico , Ácidos Oléicos/farmacología , Péptido YY , Perfusión , Peristaltismo , Conejos , Cloruro de Sodio/farmacología , Tetrodotoxina/farmacologíaRESUMEN
Intense fibrinolytic activity (FA) by granulocytes, mononuclear adherent cells, and natural killer (NK) cells was demonstrated by using 125I-fibrin-coated wells. This FA was greatly dependent on serum plasminogen, provided that serum inhibitors were destroyed by heating at 56 degrees C. Using monoclonal antibodies, it was also observed that these leukocytes produce urokinase and that this enzyme is secreted during adhesion by mononuclear adherent cells and during the cytotoxicity reaction against neoplastic cells by NK cells. Since cell intactness is necessary for leukocyte-serum interaction, stress is placed on the membrane function. We conclude that leukocytes are essential in peripheral blood FA and that transport of urokinase by circulating cells, inside their cytoplasm, could offset its lack of affinity for fibrin and thus avoid undesirable systemic effects.
Asunto(s)
Fibrinólisis , Leucocitos/fisiología , Plasminógeno/fisiología , Adhesión Celular , Técnica del Anticuerpo Fluorescente , Granulocitos/fisiología , Calor , Humanos , Células Asesinas Naturales/fisiología , Monocitos/fisiología , Activador de Plasminógeno de Tipo Uroquinasa/sangreRESUMEN
Immunological function was analyzed in mice that received daily inoculations of 5'-amino-5'-deoxythymidine (1000 mg/kg/day, i.p.) or 5-iodo-2'-deoxyuridine (100 mg/kg/day, i.p.) following antigenic stimulation. 5' Amino-5'-deoxythymidine did not suppress the development of: (1) delayed type hypersensitivity response to sheep red blood cells, (2) cell-mediated cytotoxicity response to allogeneic tumor cells, and (3) IgM and IgG antibody response to sheep red blood cells. In contrast 5-iodo-2'-deoxyuridine suppressed the development of all of these responses.