RESUMEN
BACKGROUND AND AIMS: Oxaliplatin (OX) has been described as a potential etiologic agent for porto-sinusoidal vascular disorder (PSVD). Our aim was to describe the natural history of PSVD due to OX in colon cancer (CRC) and identify risk factors for its development. METHODS: We made a multicenter retrospective case-control (ratio 1:3) study with patients diagnosed of PSVD-OX. Baseline data, end of treatment, years of follow-up and diagnosis of PSVD were collected and compared to controls (without PSVD). Besides, 16 different SNPs were selected from bibliography and analyzed by genotyping in the case group to identify potential genetic risk factors. RESULTS: 41 cases were identified, with a median time to PSVD diagnosis after the end of OX of 34 months. Spleen diameter was the strongest predictor of PSVD during treatment (OR 43.94 (14.48-133.336); p < 0.0001). Additionally, thrombocytopenia (<150 × 10^9) at one year was a significant disease risk marker (OR 9.35; 95% CI: 3.71-23.58; p = 0.001). We could not establish any significant association between the selected SNPs and PSVD diagnosis. CONCLUSION: The increase of spleen diameter is the strongest predictor of PSVD in patients treated with OX for CRC. These patients could be candidates for a specific follow-up of portal hypertension-related complications.
RESUMEN
OBJECTIVE: To compare two regimens of pantoprazole administered intravenously in patients with ulcerative gastrointestinal bleeding (UGB), and a high risk of presenting with persitent or recurrent hemorrhage. MATERIAL AND METHOD: Patients were randomized into two groups: group 0--treatment with a 80 mg bolus of pantoprazole administered intravenously, followed by continuous infusion of 8 mg/h for 72 hours; group 1--treatment with 40 mg of pantoprazole administered intravenously on a daily basis. The percentage of hemorrhagic persistence/recurrence in both groups was analyzed, as were transfusion requirements, need for surgery, and mortality resulting from the hemorrhagic episode. RESULTS: There were 20 patients in group 0 and 21 in group 1. No differences were found between groups in terms of gender, age, smoking habits, use of NSAIDs, presence of hemodynamic instability or stigmata in ulcer crater (Forrest Ia: 5 vs. 14.3%, p = 0.322; Forrest Ib: 30 vs. 33.3%, p = 0.819; Forrest IIa: 60 vs. 50.1%, p = 0.753). In group 0, 90% of patients received endoscopic treatment, versus 100% in group 1, p = 0.232. In group 0, 50% of patients had a transfusion, as compared to 52.4% in group 1, p = 0.879. In group 0, 2 patients (10.5%) presented with recurrent hemorrhage, versus 3 patients (14.3%) in group 1. Surgery was required by 1 person from each group, and 1 patient in group 0 died. CONCLUSIONS: Maximum acid inhibition with a bolus and then a continuous infusion of pantoprazole does not yield better results than treatment with conventional doses in acute hemorrhagic episodes.
Asunto(s)
2-Piridinilmetilsulfinilbencimidazoles/administración & dosificación , Úlcera Péptica Hemorrágica/tratamiento farmacológico , Inhibidores de la Bomba de Protones/administración & dosificación , Enfermedad Aguda , Femenino , Humanos , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Pantoprazol , Úlcera Péptica Hemorrágica/prevención & control , Estudios Prospectivos , Factores de Riesgo , Prevención SecundariaRESUMEN
OBJECTIVES: 1. To study transfusion requirements in the Department of Gastroenterology of a Tertiary Referral Hospital, and their evolution over the last seven years. 2. To analyze risk factors associated with greater erythrocyte transfusion requirements. PATIENTS AND METHODS: erythrocyte transfusion requirements were compared for patients admitted to the Department of Gastroenterology at Hospital Virgen del Rocío, Seville, from 1999 to 2005. Clinical data of interest have been analyzed in order to determine factors associated with greater transfusion requirements. RESULTS: 1,611 patients with a mean age of 60.45 years (59.7-61.2) were included in this study; 76.41% were males. Gastric ulcers were the cause of bleeding in 18.4% of cases (with 69% requiring transfusions); duodenal ulcers caused 22.2% of cases (with 52.9% requiring transfusions), and portal hypertension caused 33.6% of cases (with 90.2% requiring transfusions). Upper and lower gastrointestinal bleeding of unknown origin requires transfusions in 88.9 and 96.2% of cases, respectively.A multivariate logistic regression analysis showed that clinical presentations such as hematemesis (odds ratio = 3.12), hematochezia (odds ratio = 33.17), gastrointestinal hemorrhage of unknown origin (odds ratio = 6.57), and hemorrhage as a result of portal hypertension (odds ratio = 3.43) were associated with greater transfusion requirements for erythrocyte concentrates. No significant differences were observed between the percentages of patients who received transfusions from 1999 to 2005. CONCLUSIONS: 1. No differences have been observed between the percentages of patients who received transfusions over the last seven years at our Department of Gastroenterology. 2. Patients presenting with hematemesis or hematochezia, in addition to those with bleeding of unknown origin or from portal hypertension, are prone to have greater transfusion requirements.
Asunto(s)
Transfusión de Eritrocitos/estadística & datos numéricos , Hemorragia Gastrointestinal/terapia , Femenino , Hemorragia Gastrointestinal/epidemiología , Unidades Hospitalarias/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Derivación y Consulta , Estudios Retrospectivos , Factores de Riesgo , España/epidemiologíaRESUMEN
MicroRNAs (miRNAs) are small RNAs that bind to the 3 UTR of mRNAs. We are using zebra fish as a model system to study the developmental roles of miRNAs and to determine the mechanisms by which miRNAs regulate target mRNAs. We generated zebra fish embryos that lack the miRNA-processing enzyme Dicer. Mutant embryos are devoid of mature miRNAs and have morphogenesis defects, but differentiate multiple cell types. Injection of miR-430 miRNAs, a miRNA family expressed at the onset of zygotic transcription, rescues the early morphogenesis defects in dicer mutants. miR-430 accelerates the decay of hundreds of maternal mRNAs and induces the deadenylation of target mRNAs. These studies suggest that miRNAs are not obligatory components of all fate specification or signaling pathways but facilitate developmental transitions and induce the deadenylation and decay of hundreds of target mRNAs.
Asunto(s)
MicroARNs/genética , MicroARNs/metabolismo , Pez Cebra/genética , Pez Cebra/metabolismo , Animales , Secuencia de Bases , Femenino , Regulación del Desarrollo de la Expresión Génica , Masculino , Modelos Biológicos , Morfogénesis/genética , Mutación , Interferencia de ARN , Ribonucleasa III/deficiencia , Ribonucleasa III/genética , Pez Cebra/embriologíaRESUMEN
OBJECTIVE: our aims is to understand endoscopic findings from a preoperative systematic study of patients with hepatic cirrhosis who were candidates for transplantation and their impact on a protocol for primary and secondary prophylaxis of variceal haemorrhage. PATIENTS AND METHODS: this study involves a retrospective evaluation of upper digestive tract lesions detected before inclusion and a prospective evaluation of new episodes of variceal haemorrhage, associated mortality rates, and factors that are likely to be involved in the development of this condition. Primary prophylaxis with beta-blockers was considered indicated in cases of varices of grande II or greater or with signs associated with increased risk. Secondary prophylaxis was essentially always associated with medical and endoscopic treatment. RESULTS: of 134 patients, there were 9 deaths, with a median time on the waiting list of 3 months. Of all patients, 33.6% presented with high risk oesophageal varices, 11.2 % with gastric varices, 42.6% with portal hypertensive gastropathy, and 26.9% with peptic lesions. Primary prophylaxis was indicated in 33 of 90 patients, and was initiated in almost half of the cases as a results of the study. Optimum fulfiment of the pre-established objectives was 75.3%. The incidence of new haemorrhagic events due to varices was 10.4% and accounted for almost half of the deaths during the monitoring period. The only statistically significant predictive factors were the presence of gastrict varices and previous history. CONCLUSION: upper endoscopy should play a role in the preoperative examination of liver transplant candidates due to the significant impact it has on subsequent management.
Asunto(s)
Várices Esofágicas y Gástricas/diagnóstico , Hemorragia Gastrointestinal/diagnóstico , Gastroscopía/métodos , Cirrosis Hepática/cirugía , Trasplante de Hígado , Várices Esofágicas y Gástricas/epidemiología , Femenino , Hemorragia Gastrointestinal/epidemiología , Humanos , Masculino , Valor Predictivo de las Pruebas , Cuidados Preoperatorios/métodos , Evaluación de Programas y Proyectos de Salud , Estudios RetrospectivosAsunto(s)
Enfermedades de los Conductos Biliares/genética , Enfermedades de los Conductos Biliares/cirugía , Conductos Biliares Intrahepáticos , Trasplante de Hígado , Adolescente , Adulto , Enfermedades de los Conductos Biliares/diagnóstico , Niño , Femenino , Humanos , Hígado/patología , MasculinoRESUMEN
As a result of trials on a large series of compounds, one of these, N' -3-chlorobenzyl-N'-ethylurea (lozilurea, ITA 312) has shown marked anti-ulcer activity. It has shown itself to be active against chemically and neurogenically induced gastric and duodenal lesions in various experimental animal models. It has no major anti-secretory action. The experimental data obtained suggest that the mechanism of action of lozilurea consists in increasing the protective function of the mucus barrier. In the screening trials carried out in order to detect the side effects of lozilurea, it has shown sedative, antipyretic and vasodilatory actions.
Asunto(s)
Antiulcerosos , Urea/análogos & derivados , Animales , Antiulcerosos/toxicidad , Aspirina/toxicidad , Perros , Úlcera Duodenal/tratamiento farmacológico , Femenino , Mucosa Gástrica/efectos de los fármacos , Cobayas , Hexosaminas/metabolismo , Técnicas In Vitro , Indometacina/toxicidad , Masculino , Ratones , Mucoproteínas/metabolismo , Proteínas/metabolismo , Psicotrópicos , Ratas , Ratas Endogámicas , Úlcera Gástrica/inducido químicamente , Urea/farmacología , Urea/toxicidadAsunto(s)
Catárticos/metabolismo , Indoles/metabolismo , Animales , Bilis/análisis , Heces/análisis , Absorción Intestinal , Masculino , Ratas , Ratas Endogámicas , Distribución TisularRESUMEN
This paper reports on pharmacological properties of N-2-(p-chlorophenoxy)-isobutyryl-N'-morpholinomethyl-urea (plafibride, ITA 104) and its possible side effects. This work was carried out on CNS, ANS and PNS, cardiovascular system, respiratory and gastroenteric apparatus as well as anti-inflammatory activity and gastric tolerance. The most evident secondary effects were: a certain sedation, as a light tranquillizing agent, a hypothermic effect when it was administered at high doses, a certain beta-blocking and antiarrhythmic activity probably due to its local anaesthetic action. All the side effects appeared at high doses, much higher than the therapeutic ones.
Asunto(s)
Sistema Nervioso Central/efectos de los fármacos , Clofibrato/análogos & derivados , Ácido Clofíbrico/análogos & derivados , Animales , Antiinflamatorios no Esteroideos , Sistema Nervioso Autónomo/efectos de los fármacos , Temperatura Corporal/efectos de los fármacos , Sistema Cardiovascular/efectos de los fármacos , Ácido Clofíbrico/efectos adversos , Ácido Clofíbrico/farmacología , Sistema Digestivo/efectos de los fármacos , Perros , Femenino , Cobayas , Masculino , Ratones , Nervios Periféricos/efectos de los fármacos , Conejos , Ratas , Respiración/efectos de los fármacosRESUMEN
The activity of N-2-(p-chlorophenoxy)-isobutyryl-N'-morpholinomethylurea (plafibride, ITA 104) on arachidonic acid metabolism, the 3',5'-cyclic AMP-phosphodiesterase and the serum clearance of a lipid emulsion is reported in order to clarify its mechanism of action on platelet aggregation and lipid metabolism. Plafibride did not act on the arachidonic acid metabolism as far as platelet aggregation was concerned, since it did not modify the generation of prostaglandin endoperoxides nor prostacyclin. Neither did it act on the generation of thromboxane A2. Plafibride inhibited the activity of 3',5'-cyclic AMP-phosphodiesterase, which is one of the principal mechanisms of inhibition of platelet aggregation. The serum c clearance of a commercial lipid emfy the generation of prostaglandin endoperoxides nor prostacyclin. Neither did it act on the generation of thromboxane A2. Plafibride inhibited the activity of 3',5'-cyclic AMP-phosphodiesterase, which is one of the principal mechanisms of inhibition of platelet aggregation. The serum clearance of a commercial lipid emulsion was increased by plafibride which also possessed a strong hypotriglyceride activity. The correlation between platelet antiaggregant and hypolipemic activity of plafibride is discussed in this paper.
Asunto(s)
3',5'-AMP Cíclico Fosfodiesterasas/antagonistas & inhibidores , Clofibrato/análogos & derivados , Ácido Clofíbrico/análogos & derivados , Epoprostenol/biosíntesis , Hipolipemiantes/farmacología , Lípidos/sangre , Prostaglandinas/biosíntesis , Tromboxanos/biosíntesis , Animales , Bovinos , Ácido Clofíbrico/farmacología , Inhibidores de la Ciclooxigenasa , Depresión Química , Emulsiones Grasas Intravenosas , Técnicas In Vitro , Cinética , Ratas , Ratas Endogámicas , Tromboxano A2/metabolismoRESUMEN
The disodium salt of the sulphuric diester of 3,3-bis-(4-hydroxyphenyl)-7-methyl-2-indolinone (sodium sulisatin, Laxitex), a synthetic laxative with two phenolic groups esterified with sulfate, has been studied in order to find out if its laxative properties may be attributed to the unaltered compound or to its diphenolic derivative BHMI. We first studied the effect of homogenates of the gastrointestinal tract of rats and of rat cecal content of the hydrolysis of sulfate ester bonds of sulisatin. Results show that sulisatin can be hydrolyzed by cecal content while homogenates of stomach, small intestine and large intestine have no hydrolytic effect. Sulisatin is also a substrate of arylsulfate sulphohydrolase obtained from the snail Helix pomatia. The unaltered drug has no effect on the intestinal motility since it does not change the intestinal transit speed in rats pretreated with neomycin sulfate. Sulisatin (1.5, 3 and 6 mg) is unable to inhibit water absorption in rat colon while small amounts of BHMI (15 and 30 micrograms) may inhibit it significantly. It is concluded that sulisatin passes unaltered through the small intestine and is hydrolyzed in the large intestine by the intestinal microflora to its diphenolic derivative BHMI, which is responsible for the laxative activity of the drug.
Asunto(s)
Catárticos/metabolismo , Indoles/metabolismo , Fenoles/metabolismo , Animales , Arilsulfatasas/metabolismo , Biotransformación , Catárticos/farmacología , Heces/análisis , Mucosa Gástrica/metabolismo , Motilidad Gastrointestinal/efectos de los fármacos , Técnicas In Vitro , Indoles/farmacología , Absorción Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Masculino , Neomicina/farmacología , Fenoles/farmacología , Ratas , Factores de TiempoAsunto(s)
Antiinflamatorios/uso terapéutico , Feprazona/análogos & derivados , Fenilbutazona/análogos & derivados , Animales , Artritis/tratamiento farmacológico , Artritis Experimental/tratamiento farmacológico , Perros , Feprazona/farmacología , Feprazona/uso terapéutico , Mucosa Gástrica/efectos de los fármacos , Granuloma/tratamiento farmacológico , Cobayas , Ratones , Pleuresia/tratamiento farmacológico , RatasRESUMEN
A technique for testing antianginal drugs has been developed measuring hemodynamic variables, such as heart rate, left ventricular pressure and its dp/dt, aortic root and coronary sinus pressure, Veragut's index and area under the curve of LVP and metabolic variables, such as A-V difference of oxygen and lactate, oxygen content in coronary sinus, percentage extraction of oxygen, excess lactate. Physiological experimental conditions included spontaneously breathing dogs, catheters introduced under X-rays control and closed chest. A commentary about activity criteria, usefulness and inconvenients of this technique is presented.