RESUMEN
A considerable incidence of colonic strictures after oncologic low anterior resections has been reported. The present paper describes a colonic stricture 5 years after the surgery, and not related to radiotherapy, that required a challenging differential diagnosis with local recurrence of rectal cancer. The role of endoscopy in the management of this condition is discussed.
Asunto(s)
Colitis Isquémica/complicaciones , Enfermedades del Colon/diagnóstico , Enfermedades del Colon/etiología , Obstrucción Intestinal/diagnóstico , Obstrucción Intestinal/etiología , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Recto/cirugía , Anciano , Humanos , Masculino , Factores de TiempoRESUMEN
TNF alpha seems to play an important role in the pathogenesis of adult respiratory distress syndrome. We studied the effect of TNF alpha on phospholipid synthesis by isolated type II pneumocytes and attempted to characterize the role of arachidonate metabolites and the influence of pentoxifylline on such an effect. Lung tissue obtained from both multiple organ donors (n = 14) and lung cancer patients (n = 11) was used for cell isolation. Surfactant synthesis was measured by the incorporation of D-[U-14C]glucose into phosphatidylcholine (PC). The basal PC synthesis was higher in the donor group than in the malignant group (3.44 +/- 0.19 vs 2.15 +/- 0.15 pmol/microgram protein x 120 min, P < 0.01), and, in the presence of 100 ng/ml of TNF alpha, the incorporation of labeled glucose into PC was reduced significantly in both donor (1.13 +/- 0.11 vs 3.44 +/- 0.19 pmol/microgram protein x 120 min, P < 0.01) and cancer (0.99 +/- 0.11 vs 2.15 +/- 0.15 pmol/microgram protein x 120 min, P < 0.01) groups. Indomethacin was able to completely block the cytokine-induced decrease in PC synthesis by pneumocytes from the malignant group and to attenuate the inhibitory effect of TNF alpha in those from donors, nordihydroguaiaretic acid having a similar effect. The TNF alpha effect can be blocked by pentoxifylline (100 micrograms/ml), a substance which can even succeed in reverting the basal secretory inhibition of cancer patients' pneumocytes to levels similar to those of the donor group. TNF alpha may contribute to the pathophysiology of adult respiratory distress syndrome by inhibiting the synthesis of surfactant. TNF alpha might be produced in lung tumors, resulting in chronic paracrine or systemic exposure of pneumocytes to low concentrations of the cytokine. The TNF alpha effect was not prevented completely by the blockage of the arachidonic acid metabolism, hence other mediators should also be implicated.
Asunto(s)
Pulmón/metabolismo , Fosfatidilcolinas/biosíntesis , Prostaglandinas/fisiología , Síndrome de Dificultad Respiratoria/etiología , Factor de Necrosis Tumoral alfa/farmacología , Adulto , Factores de Edad , Ácido Araquidónico/metabolismo , Humanos , Técnicas In Vitro , Indometacina/farmacología , Pulmón/citología , Masculino , Persona de Mediana Edad , Pentoxifilina/farmacologíaRESUMEN
Breast cancer gastrointestinal and soft tissue metastases are extremely rare. We present the case of a woman with perianal metastases from a primary lobular breast carcinoma 11 years after mastectomy and local radiotherapy.
Asunto(s)
Canal Anal , Neoplasias de la Mama/patología , Carcinoma Lobular/patología , Neoplasias Intestinales/secundario , Canal Anal/patología , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Carcinoma Lobular/radioterapia , Carcinoma Lobular/cirugía , Femenino , Humanos , Persona de Mediana Edad , Invasividad NeoplásicaRESUMEN
BACKGROUND: The growing popularity in western countries of eating uncooked seafood has resulted in an increased incidence of anisakidosis. AIM: To study the in vitro activity of different concentrations of albendazole against Anisakis simplex larvae under different media pH. METHODS: A. simplex larvae were obtained from fresh hakes acquired from the fish market of Madrid. They were divided into groups and placed in culture dishes (15 larvae each) containing RPMI-1640, in the presence or absence of different concentrations of albendazole (300, 400 and 500 microg/mL). RESULTS: Albendazole dose-dependently reduced the survival of the larvae, its maximum activity being at 500 microg/mL when it killed almost all larvae at 48 h. Acidic medium pH significantly reduced the efficacy of albendazole. CONCLUSION: Albendazole is effective in killing A. simplex larvae at different pH in vitro, suggesting that this molecule could be useful in treating clinical manifestations of human anisakidosis.
Asunto(s)
Albendazol/farmacología , Anisakis/efectos de los fármacos , Antihelmínticos/farmacología , Albendazol/administración & dosificación , Animales , Antihelmínticos/administración & dosificación , Relación Dosis-Respuesta a Droga , Concentración de Iones de HidrógenoRESUMEN
The main aim of this study was to evaluate the clinical relevance of Gelatinases in colorectal cancer (CRC). Ninety-five CRCs and their paired normal tissues were investigated to detect total levels of MMP-9, MMP-2, and the tissue inhibitors TIMP-1 and TIMP-2. Also, pro-MMP and MMP activity, and potential associations with clinical parameters were estimated. MMP-9, MMP-2 and TIMP-1 levels were greater in CRCs than in normal tissues, differences being significant for MMP-9 and TIMP-1. However, TIMP-2 showed significantly lower levels in tumour samples. Moreover, significant differences in the state of activation between gelatinases were found. TIMP-1 low levels were significantly associated with poor clinical outcome of patients. According to these data, different roles have to be attributed to MMP-2 and MMP-9 in CRC progression. Moreover, TIMP-1 level evaluation emerges as the main prognostic factor in relation to Gelatinases A and B activity in CRC.
Asunto(s)
Neoplasias Colorrectales/diagnóstico , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Inhibidor Tisular de Metaloproteinasa-1/metabolismo , Inhibidor Tisular de Metaloproteinasa-2/metabolismo , Adenocarcinoma/diagnóstico , Adenocarcinoma/enzimología , Adenocarcinoma/metabolismo , Anciano , Neoplasias Colorrectales/enzimología , Neoplasias Colorrectales/metabolismo , Regulación hacia Abajo , Femenino , Humanos , Masculino , Metaloproteinasa 2 de la Matriz/análisis , Metaloproteinasa 9 de la Matriz/análisis , Persona de Mediana Edad , Pronóstico , Inhibidor Tisular de Metaloproteinasa-1/análisis , Inhibidor Tisular de Metaloproteinasa-2/análisis , Regulación hacia ArribaRESUMEN
AIM: The aim of the present study is to evaluate the prognostic influence of loss of heterozygosity on 2p, 3p, 5q, 17p and 18q, and c-myc overexpression on surgically treated sporadic colorectal carcinoma. METHODS: Tumor and non-tumor tissue samples from 153 patients were analyzed. Fifty-one percent of patients were male, and mean age in the series was 67 years. Tumors were located in the proximal colon in 37 cases, in the distal bowel in 37, and in the rectum in 79 patients. c-myc overexpression was studied by means of Northern blot analysis, and loss of heterozygosity through microsatellite analysis. RESULTS: c-myc overexpression was detected in 25% of cases, and loss of heterozygosity in at least one of the studied regions in 48%. There was no association between clinical and pathologic features, and genetic alterations. The disease-free interval was significantly shorter for patients with both genetic alterations; the presence of both events was an independent prognostic factor for poor outcome in the multivariate analysis (RR: 4.34, p < 0.0001). CONCLUSIONS: The presence of both loss of heterozygosity and overexpression of the c-myc oncogene separates a subset of colorectal carcinoma patients who have a shorter disease-free interval after curative-intent surgery.
Asunto(s)
Neoplasias Colorrectales/genética , Genes myc , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/cirugía , Femenino , Expresión Génica , Humanos , Pérdida de Heterocigocidad , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
Several distinct genetic alterations have been associated with colorectal tumorigenesis. This study investigated the frequency of microsatellite instability, also known as replication error (RER), and loss of heterozygosity (LOH) at six chromosome regions in sporadic colorectal cancer (CRC). Eighty-six tumour and paired normal mucosa samples were included in the study. A polymerase chain reaction (PCR)-based technique was performed to analyse six (CA)n dinucleotide repeats located near or within regions containing important genes implicated in the complex process of colorectal tumorigenesis (chromosomes 2p, 3p, 5q, 11p, 17p and 18q). Overall, LOH frequency was higher in RER-tumours (25/46, 54.3%) compared with RER+ tumours (9/40, 22.5) (P = 0.04). To investigate prognostic implications, survival analysis was performed for 66 patients. Compared with RER- tumours, patients with RER+ tumours at 2p, 3p, 5q, 11p or 18q were found to have an improved prognosis (overall survival, P = 0.02 and disease-free survival (DFS) P = 0.005) this variable being an independent prognostic factor by multivariate analysis (P = 0.001). Overall survival of patients whose tumours were LOH+ was significantly shorter compared with those without LOH (overall survival, P = 0.008 and DFS, P = 0.01). Thus, tumours displaying RER+ and LOH+ phenotype, as established by microsatellite analysis, show a differential prognosis. These data indicate that this may be a useful tool for the identification of patients at different risks affected by CRC.
Asunto(s)
Neoplasias Colorrectales/genética , Pérdida de Heterocigocidad/genética , Anciano , Replicación del ADN , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Repeticiones de Microsatélite , Análisis Multivariante , Fenotipo , Reacción en Cadena de la Polimerasa/métodos , PronósticoRESUMEN
We have studied 61 resected colorectal adenocarcinomas in order to investigate p53 mutations as a prognostic factor for this pathology. Mutations in exons 5-9 of the p53 gene were analyzed by the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) technique followed by sequencing. Our data indicate that p53 exon 7 mutations were prevalent in the latest stages of colorectal carcinogenesis and patients bearing this alteration had the worst prognosis. Therefore, according to our results, mutations affecting exon 7 of the p53 gene could be considered as a useful marker of biological aggressiveness for colorectal cancer.
Asunto(s)
Neoplasias Colorrectales/genética , Exones/genética , Genes p53/genética , Mutación Puntual , Anciano , Análisis de Varianza , Neoplasias Colorrectales/patología , Femenino , Humanos , Masculino , Estadificación de Neoplasias , Polimorfismo Conformacional Retorcido-Simple , Pronóstico , Modelos de Riesgos Proporcionales , Análisis de SupervivenciaRESUMEN
We have evaluated telomerase activity in a tumour population of 65 human cancers by using a TRAP-based method, in which detection is performed by an enzyme immunoassay (ELISA). We have corroborated that sensitivity and specificity of this new procedure can be considered similar to that of classical TRAP method, having the advantage of a rapid and reproducible analysis of large pools of samples. Thus, telomerase activity was detected in 83% of the tumours included in our population. Moreover, we found a significant association between enzyme activity and both hTR and hTERT expression (P=0.004 and P=0.04, respectively).
Asunto(s)
Neoplasias/enzimología , ARN , Telomerasa/metabolismo , Proteínas de Unión al ADN , Ensayo de Inmunoadsorción Enzimática , Humanos , ARN Mensajero/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sensibilidad y Especificidad , Telomerasa/genéticaRESUMEN
Surfactant protein A (SP-A) is thought to play a role in the modulation of lung inflammation during acute respiratory distress syndrome (ARDS). However, SP-A has been reported both to stimulate and to inhibit the proinflammatory activity of pulmonary macrophages (Mphi). Because of the interspecies differences and heterogeneity of Mphi subpopulations used may have influenced previous controversial results, in this study, we investigated the effect of human SP-A on the production of cytokines and other inflammatory mediators by two well-defined subpopulations of human pulmonary Mphi. Surfactant and both alveolar (aMphi) and interstitial (iMphi) macrophages were obtained from multiple organ donor lungs by bronchoalveolar lavage and enzymatic digestion. Donors with either recent history of tobacco smoking, more than 72 h on mechanical ventilation, or any radiological pulmonary infiltrate were discarded. SP-A was purified from isolated surfactant using sequential butanol and octyl glucoside extractions. After 24-h preculture, purified Mphi were cultured for 24 h in the presence or absence of LPS (10 microg/mL), SP-A (50 microg/mL), and combinations. Nitric oxide and carbon monoxide (CO) generation (pmol/microg protein), cell cGMP content (pmol/microg protein), and tumor necrosis factor alpha (TNFalpha), interleukin (IL)-1, and IL-6 release to the medium (pg/microg protein) were determined. SP-A inhibited the lipopolysaccharide (LPS)-induced TNFalpha response of both interstitial and alveolar human Mphi, as well as the IL-1 response in iMphi. The SP-A effect on TNFalpha production could be mediated by a suppression in the LPS-induced increase in intracellular cGMP. In iMphi but not in aMphi, SP-A also inhibited the LPS-induced IL-1 secretion and CO generation. These data lend further credit to a physiological function of SP-A in regulating alveolar host defense and inflammation by suggesting a fundamental role of this apoprotein in limiting excessive proinflammatory cytokine release in pulmonary Mphi during ARDS.
Asunto(s)
Citocinas/metabolismo , Macrófagos Alveolares/efectos de los fármacos , Macrófagos Alveolares/metabolismo , Proteolípidos/farmacología , Surfactantes Pulmonares/farmacología , Adulto , Líquido del Lavado Bronquioalveolar/citología , Monóxido de Carbono/metabolismo , Células Cultivadas , GMP Cíclico/análogos & derivados , GMP Cíclico/metabolismo , GMP Cíclico/farmacología , Citocinas/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Humanos , Lipopolisacáridos/farmacología , Masculino , Persona de Mediana Edad , Óxido Nítrico/metabolismo , Proteolípidos/metabolismo , Proteína A Asociada a Surfactante Pulmonar , Proteínas Asociadas a Surfactante Pulmonar , Surfactantes Pulmonares/metabolismo , Transducción de Señal , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
BACKGROUND: We sought to assess the relationship between tissue concentration of erb -b-2 or neu oncogene-encoded protein (p185(neu)) with overall survival in patients with non-small cell lung cancer. METHODS: Levels of protein p185(neu) were determined in 102 patients with the diagnosis of non-small cell lung cancer. Concentration of p185(neu) protein was determined by using enzyme immunoassay and evaluated by using several variables. The relative prognostic importance of this marker and its influence on other prognostic factors was evaluated by using the Cox regression model. RESULTS: The mean p185(neu) value in these samples was 250 +/- 200 U/mg (95% confidence interval, 210-290). This distinguished two groups within the tumoral population: those with less than 350 U/mg and those with 350 U/mg or greater (80th percentile). Multivariable analysis established an independent prognostic value for protein p185(neu). Patients with p185(neu) values of the 80th percentile or greater had a risk of death that was 2.11-fold (95% confidence interval, 1.10-4.05) that of patients with values of less than 350 U/mg (P =.03), and increases in the neu oncogene of 100 U/mg increased the probability of death by 17% (P =.02; 95% confidence interval, 1.04-1.31). CONCLUSION: This study shows that the p185(neu) expression is an objective and comparable variable for the assessment of phenotypic aggressivity in non-small cell lung cancer, and in the future, it could be included in daily clinical practice.
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Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Neoplasias Pulmonares/metabolismo , Receptor ErbB-2/biosíntesis , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/química , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Femenino , Humanos , Neoplasias Pulmonares/química , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Receptor ErbB-2/análisis , Tasa de SupervivenciaRESUMEN
BACKGROUND: Tumor necrosis factor alpha (TNF-alpha)-induced inhibition of surfactant synthesis seems to participate in the pathogenesis of the adult respiratory distress syndrome. OBJECTIVES: To examine the ability of human type II pneumocytes to produce nitric oxide (NO) in the presence of TNF-alpha and, in addition, to explore the role of this radical in the transduction of the cytokine signal. DESIGN: Multiple organ donors were the source of lung tissue specimens. Type II pneumocytes were isolated by enzymatic digestion, adherence separation of macrophages, and gradient purification. After 24-hour preculture, cells were cultured for 24 hours in the presence or absence of TNF-alpha (100 ng/mL), sodium nitroprusside (100 mumol/L), N omega-nitro-L-arginine methyl ester (NAME) (1 mmol/L), methylene blue (10 mumol/L),8-bromo-3',5'-cyclic guanosine monophosphate (8-Br-cGMP) (1 mmol/L), prostaglandin E2 (PGE2) (0.1 mumol/L), indomethacin (30 mumol/L), and combinations. The NO release to the medium and cGMP and PGE2 contents of the cells were measured. RESULTS: The incorporation of 14C-labeled glucose (D-[U-14C]glucose) into phosphatidylcholine and phosphatidylglycerol was selectively inhibited either by 8-Br-cGMP or in the presence of TNF-alpha, PGE2, or nitroprusside, all of which caused an increase in the intracellular levels of cGMP. The inhibitory effect of TNF-alpha was partially reverted by indomethacin, NAME, N-monomethyl arginine, or methylene blue. The inhibitory effect of PGE2 was partially reverted by NAME, while that of nitroprusside was reverted by methylene blue, but not by indomethacin. Tumor necrosis factor alpha induced an increase in PGE2 (4.31 +/- 0.27 vs 1.65 +/- 0.17-pg/microgram protein, n = 10, P < .01) and cGMP (0.238 +/- 0.012 vs 0.109 +/- 0.014-pmol/microgram protein, n = 10, P < .01) cell content and in the NO release to the medium (3.10 +/- 0.14 vs 1.19 +/- 0.11-nmol/microgram protein, n = 10, P < .01). The basal NO release to the medium was also increased in the presence of PGE2. The NAME, which blocked NO generation and cGMP increase, did not affect PGE2 production in response to TNF-alpha. However, indomethacin, which blocked PGE2 production, also blunted NO generation and cGMP increase. CONCLUSIONS: The NO generation, secondary to PGE2 production, seems responsible for the TNF-alpha-induced inhibition of phosphatidylcholine synthesis by human type II pneumocytes. Nitric oxide seems to exert this effect through activation of guanylyl cyclase.
Asunto(s)
Dinoprostona/fisiología , Pulmón/metabolismo , Óxido Nítrico/fisiología , Surfactantes Pulmonares/biosíntesis , Factor de Necrosis Tumoral alfa/fisiología , Adolescente , Adulto , Cadáver , Células Cultivadas , Dinoprostona/biosíntesis , Humanos , Pulmón/citología , Persona de Mediana Edad , Óxido Nítrico/biosíntesis , Fosfatidilcolinas/biosíntesis , Surfactantes Pulmonares/antagonistas & inhibidores , Transducción de Señal/fisiologíaRESUMEN
BACKGROUND AND OBJECTIVES: The second messenger cyclic guanosine 3',5'-monophosphate (cGMP) seems to be implicated in the release of tumor necrosis factor alpha (TNF-alpha) by activated macrophages. There is controversy regarding the potential of human macrophages to produce nitric oxide (NO). Since guanylate cyclase can be activated also by carbon monoxide (CO) and this gas may be formed endogenously, we examined the ability of human pulmonary macrophages to produce CO in the presence of lipopolysaccharide (LPS) or LPS+interferon gamma (IFN-gamma). In addition, the source and the relative contribution of this molecule to the LPS-induced increase in cell cGMP content and TNF-alpha release were explored. DESIGN: Interstitial macrophages were obtained from multiple organ donor lungs by enzymatic digestion. After 24-hour preculture, purified macrophages were cultured for 24 hours in the presence or absence of LPS, LPS+IFN-gamma, CO (250 and 500 mumol/L), sodium nitroprusside, 8-Br-cGMP, hemoglobin, methylene blue, zinc-protoporphyrin IX, hemin, S-adenosylmethionine, deferoxamine mesylate, or combinations. The cGMP content of the cells and TNF-alpha, CO, and NO release to the medium were determined. RESULTS: In the presence of LPS, TNF-alpha production was not accompanied by any detectable increase in the NO release to the medium. However, an increase in medium CO concentration (mean +/- SEM) (5.81 +/- 0.20 vs 3.74 +/- 0.08 pmol/microgram protein; n = 11; P < .01) and cell cGMP content (0.273 +/- 0.021 vs 0.138 +/- 0.019 pmol/microgram protein; n = 10; P < .01) was observed. These changes were more pronounced in the presence of LPS+IFN-gamma. Release of TNF-alpha also was induced by both sodium nitroprusside and 8-Br-cGMP. In contrast, methylene blue, a guanylate cyclase inhibitor, inhibited LPS-, LPS+IFN-gamma-, and sodium nitroprusside-induced TNF-alpha production and cGMP increase; hemoglobin, which traps CO, had a similar effect. CONCLUSION: Intracellular cGMP increase, secondary to an endogenous production of CO, participates in the release of TNF-alpha by activated human pulmonary macrophages.
Asunto(s)
Monóxido de Carbono , GMP Cíclico/metabolismo , Macrófagos Alveolares/metabolismo , Transducción de Señal/fisiología , Factor de Necrosis Tumoral alfa/biosíntesis , Adolescente , Adulto , Monóxido de Carbono/metabolismo , Monóxido de Carbono/farmacología , Células Cultivadas , Humanos , Interferón gamma , Lipopolisacáridos , Activación de Macrófagos , Macrófagos Alveolares/efectos de los fármacos , Persona de Mediana Edad , Óxido Nítrico/metabolismoRESUMEN
BACKGROUND: An increase in cyclic guanosine 3',5'-monophosphate (cGMP) due to nitric oxide generation is known to participate in the mediation of the tumor necrosis factor alpha (TNF-alpha) effect in type II cells. Because guanylyl cyclase can be activated also by carbon monoxide (CO), in this study we examined the ability of human type II pneumocytes to produce CO in the presence of cytokines and the relative contribution of this molecule to the TNF-alpha and interleukin 1 effects. DESIGN: Type II pneumocytes were isolated from cadaveric multiple-organ donors by enzymatic digestion, adherence separation of macrophages, and gradient purification. After preculture for 24 hours, cells were cultured for 24 hours in the presence or absence of TNF-alpha, interleukin 1, sodium nitroprusside, N(omega)-nitro-1-arginine, CO, hemin, zinc-protoporphyrin type IX, deferoxamine mesylate, S-adenosyl-L-methionine, alpha-tocopherol, methylene blue (a guanylyl cyclase inhibitor), 8-bromine-cGMP, and combinations of these reagents. Both CO (picomole per microgram of protein) and nitric oxide release to the medium and the cGMP (picomole per microgram of protein) content of the cells were measured. In a different set of experiments, D-glucose labeled with radioactive carbon (14C) was added to the medium, and the labeling of several lipid fractions was determined (picomole per microgram of protein). RESULTS: D-[14C]glucose incorporation into phosphatidylcholine, the main surfactant component, was selectively inhibited in the presence of cytokines, CO, sodium nitroprusside, or 8-bromine-cGMP. The inhibitory effect of TNF-alpha was partially reversed by N(omega)-nitro-L-arginine, deferoxamine, or alpha-tocopherol and totally reversed by methylene blue. Tumor necrosis factor alpha induced an increase in cGMP cell content and in the CO and nitric oxide release to the medium. Hemin increased CO and cGMP production and decreased phosphatidylcholine synthesis. Zinc-protoporphyrin type IX, an inhibitor of heme oxygenase, and all 3 antioxidants, which inhibited CO production, also antagonized the TNF-alpha effect on cGMP and phosphatidylcholine synthesis. CONCLUSIONS: Intracellular cGMP increase due to an endogenous generation of both CO and nitric oxide mediates the cytokine-induced inhibition of surfactant synthesis by type II pneumocytes. Both lipid peroxidation and heme oxygenase activity are sources for the observed CO production.
Asunto(s)
Monóxido de Carbono/farmacología , Alveolos Pulmonares/efectos de los fármacos , Alveolos Pulmonares/metabolismo , Surfactantes Pulmonares/biosíntesis , Adolescente , Adulto , Cadáver , Células Cultivadas , Hemo Oxigenasa (Desciclizante) , Humanos , Peroxidación de Lípido , Masculino , Persona de Mediana Edad , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
To evaluate the effectiveness of treatment with total parenteral nutrition (TPN) alone (group A) or combined with continuous intravenous infusion of somatostatin (group B) in postoperative gastrointestinal fistulas, a multicenter, controlled and prospective randomized trial was designed. We present the results obtained after the evaluation of 40 cases (group A, n = 20; group B, n = 20). No significant differences among these treatment schedules were observed in the percentage of closure of fistulas (group A, 81.25%; group B, 85%), but patients treated with total parenteral nutrition plus somatostatin had the fistulas close within a significantly shorter period of time. Moreover, this treatment was associated with a significantly lower morbidity. These preliminary results indicate that somatostatin is a useful therapeutic complement in the conservative treatment of patients with gastrointestinal fistulas.
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Fístula Intestinal/tratamiento farmacológico , Fístula Pancreática/tratamiento farmacológico , Somatostatina/uso terapéutico , Adulto , Anciano , Femenino , Humanos , Fístula Intestinal/etiología , Fístula Intestinal/terapia , Masculino , Persona de Mediana Edad , Fístula Pancreática/etiología , Fístula Pancreática/terapia , Nutrición Parenteral Total , Complicaciones Posoperatorias/terapia , Estudios ProspectivosRESUMEN
Interleukin-1, tumor necrosis factor, and interleukin-6 inhibit insulin release and may be cytotoxic to isolated pancreatic islets. These cytokines have been postulated to play an important role in the beta cell destruction characteristic of type 1 diabetes. The present study was designed to investigate the effect of the above cytokines on insulin, glucagon, somatostatin, and thyrotropin-releasing hormone secretion by isolated human islets. In addition, we have investigated if cytokine-induced modifications in hormone secretion are accompanied by modifications in the ab initio synthesis of any specific lipidic fraction. All three cytokines studied, although not modifying insulin and somatostatin release to glucose 5 mmol/L, inhibited the response of both hormones to glucose 20 mmol/L. On the other hand, the cytokines almost completely blocked islet basal glucagon release, without affecting thyrotropin-releasing hormone secretion. The added cytokines also suppressed 20 mmol/L [U-14C]glucose incorporation into both phospholipids and diacylglycerol. Our results demonstrate a beta-, alpha-, and delta-cell, sensitivity to cytokine action. Additionally, they suggest that ab initio lipid synthesis might be implicated in the mechanism of insulin release in human islets.
Asunto(s)
Citocinas/farmacología , Hormonas/metabolismo , Islotes Pancreáticos/efectos de los fármacos , Lípidos/biosíntesis , Adolescente , Adulto , Glucagón/metabolismo , Humanos , Insulina/metabolismo , Secreción de Insulina , Interleucina-1/farmacología , Interleucina-6/farmacología , Islotes Pancreáticos/metabolismo , Persona de Mediana Edad , Hormona Liberadora de Tirotropina/metabolismo , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
Tumor necrosis factor (TNF alpha) has been shown to inhibit insulin release and it has been postulated to-be an important effector in islet rejection. We studied the effect of cryopreservation on glucose oxidation rate (GOR), lipid synthesis, hormone secretion (insulin, glucagon, somatostatin, thyrotropin-releasing hormone), and cyclic guanosine 3',5'-monophosphate (cGMP) content of human islets, in the presence or absence of TNF alpha, looking for changes that could explain a different susceptibility to rejection for cryopreserved islets. Islets were isolated from multiple organ donor pancreata by collagenase digestion. The islets were then cultured for 7 days, cryopreserved (-0.25 degrees C/min), and stored in liquid N2. After 24 h of culture, thawed islets were cultured for an other 24 h in the presence or absence of TNF alpha. Islets were then washed to remove the cytokine and incubated in Krebs-Ringer bicarbonate (5 or 20 mM glucose), and both the cGMP content of the islets and the hormone concentration in the medium were determined by radio-immunoassay. GOR was measured as the production of 14CO2 from 5 or 20 mM D-[U-14C]glucose, and de novo lipid synthesis was determined as D-[U-14C]glucose incorporation into different lipidic fractions. Cryopreservation did not significantly modify the hormone response to glucose but it partially reversed the TNF alpha-induced inhibitory effect on insulin release in the presence of 20 mM glucose. In addition, the inhibitory effect of TNF alpha on phosphatidylcholine labeling was attenuated in cryopreserved islets compared with noncryopreserved islets. TNF alpha significantly stimulated islet nitrite production and cGMP accumulation, both effects being of a similar magnitude in cryopreserved and noncryopreserved islets. Our results suggest that cryopreservation can modify the metabolic and hormone response of human islets to TNF alpha. This effect is not mediated by changes in the TNF alpha-induced islet nitric oxide production or cGMP accumulation.
Asunto(s)
Criopreservación , Islotes Pancreáticos/efectos de los fármacos , Islotes Pancreáticos/fisiología , Factor de Necrosis Tumoral alfa/farmacología , Adolescente , Adulto , AMP Cíclico/metabolismo , GMP Cíclico/metabolismo , Resistencia a Medicamentos , Glucosa/metabolismo , Humanos , Técnicas In Vitro , Insulina/metabolismo , Secreción de Insulina , Islotes Pancreáticos/metabolismo , Trasplante de Islotes Pancreáticos , Lípidos/biosíntesis , Persona de Mediana Edad , Nitritos/metabolismo , Oxidación-Reducción , Somatostatina/metabolismoRESUMEN
The aim of the present study was to analyze the prevalence and clinical importance of p53 gene mutations in surgically treated squamous cell lung carcinoma. Sixty patients were included. Fifty-one patients in stages I to IIIa were submitted to radical resection. Twenty-five samples tested positive for the p53 immunohistochemistry assay, and were analyzed for p53 gene mutations. Eleven mutations were found. Patients harboring p53 gene mutations suffered a higher incidence of recurrence and a higher mortality rate. Disease-free interval and overall survival were shorter for patients with mutated p53 gene (p=0.03 and p=0.005, respectively).
Asunto(s)
Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Genes p53 , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Mutación Puntual , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/cirugía , ADN de Neoplasias/química , ADN de Neoplasias/genética , Supervivencia sin Enfermedad , Humanos , Inmunohistoquímica , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/cirugía , Persona de Mediana Edad , Estadificación de Neoplasias , Reacción en Cadena de la Polimerasa , Polimorfismo Conformacional Retorcido-Simple , Pronóstico , Análisis de Supervivencia , Proteína p53 Supresora de Tumor/análisisRESUMEN
The prognostic information provided by preoperative serum CEA and CA 19.9 antigen assay on the postoperative outcome of 150 patients with colorectal cancer was analysed. The influence of both markers was studied by Cox's proportional-hazard regression analysis. In the univariate analysis, patients whose initial CA 19.9 level was higher than 37 U/ml had a 4.32-fold greater risk of death due to the cancer (95% CI: 1.72-10.84) (p < 0.001) than patients with lower values. The 36-month survival rate posttreatment was lower for patients with CA 19.9 serum levels over 37 U/ml (61% versus 90%) (p < 0.001). Patients whose initial CEA level was higher than 5 ng/ml had a 2.9-fold greater risk of death (95% CI: 1.05-7.99) (p = 0.04) than patients with lower values. The 36-month survival rate posttreatment was lower for patients with CEA serum levels over 5 ng/ml (84% versus 76%) (p = 0.04). After adjustment for Dukes' stage, CEA, CA 19.9, tumor site, sex and age, only Dukes' stage and CA 19.9 continued to provide independent predictive information on survival. The risk of death increases by 1.008 for every 10 U/ml rise in the level of the marker (95% CI: 1.002-1.014) (p = 0.009). With respect to analysis of disease-free survival, only Dukes' stage provided independent predictive value. CA 19.9 is an independent prognostic factor of survival in colorectal cancer. The authors suggest including CA 19.9 in a future multifactorial analysis of survival.
Asunto(s)
Antígeno CA-19-9/sangre , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/cirugía , Factores de Edad , Anciano , Antígeno Carcinoembrionario/sangre , Neoplasias del Colon/sangre , Neoplasias del Colon/cirugía , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Pronóstico , Modelos de Riesgos Proporcionales , Neoplasias del Recto/patología , Neoplasias del Recto/cirugía , Factores Sexuales , Tasa de Supervivencia , Factores de TiempoRESUMEN
The relationship between serum and cytosolic levels of carcinoembryonic (CEA), squamous-cell carcinoma (SCC) and CA125 antigens was determined in 122 patients with non-small cell lung cancer. A pronounced serum-cytosol gradient and a high degree of dispersion in the distribution of serum and cytosol marker concentrations was detected. In addition, the degree of concordance between TM levels in the two compartments, determined by the intraclass correlation coefficient (ICC) index, was low (ICC = 0.42 for CEA; 0.35 for CA 125; and 0.27 for SCC). Tumour stage and histological type both played a limited role in the serum-cytosol relationship. As tumour stage advanced, the concordance between serum and cytosolic TM level became more pronounced. In addition, each histological type showed a distinctive pattern of expression of serum and cytosolic tumour markers, and a specific degree of concordance between levels in serum and cytosol. However, the ICC indices were always under 0.51, indicating that the importance of these factors is minor. The data obtained indicate that the relationship between serum and cytosolic concentration is moderate. The differences found according to stage grouping and histological subtype are so small that no clear-cut message for clinical practice can be drawn.