Clinical and genetic factors involved in Porto-sinusoidal vascular disorder after oxaliplatin exposure.

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.

[Intravenous proton-pump inhibitor for acute peptic ulcer bleeding--is profound acid suppression beneficial to reduce the risk of rebleeding?]. / Inhibidores de la bomba de protones por vía intravenous en la hemorragia por úlcera péptica: es necesaria la supresión ácida máxima para disminuir el resangrado?

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.

Inhibidores de la bomba de protones por vía intravenosa en la hemorragia por úlcera péptica: ¿es necesaria la supresión ácida máxima para disminuir el resangrado? / No disponible

Objetivo: comparar dos pautas de pantoprazol por vía intravenosaen pacientes con hemorragia digestiva alta (HDA) ulcerosade alto riesgo para presentar persistencia o recidiva hemorrágica.Material y método: se randomizaron los pacientes en dosgrupos: grupo 0: tratamiento con bolo de 80 mg i.v. de pantoprazoly perfusión continua a 8 mg/h durante 72 horas; grupo 1: tratamientocon 40 mg i.v. de pantoprazol diarios. Se analizó el porcentajede persistencia/recidiva hemorrágica entre ambos grupos,requerimientos transfusionales, necesidad de cirugía y mortalidaddel episodio hemorrágico.Resultados: se incluyeron 20 pacientes en el grupo 0 y 21en el grupo 1. No se encontraron diferencias entre ambos gruposen cuanto al sexo, edad, hábito tabáquico, consumo de AINE,presencia de inestabilidad hemodinámica, estigma sobre el nichoulceroso (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). El 90%de los pacientes del grupo 0 recibió tratamiento endoscópico vs.el 100% del grupo 1, p = 0,232. El 50% de los pacientes del grupo0 recibió transfusión vs. el 52,4% del grupo 1, p = 0,879. Dospacientes (10,5%) del grupo 0 presentaron recidiva hemorrágicavs. 3 pacientes (14,3%) del grupo 1, precisando cirugía 1 pacientede cada grupo y falleciendo 1 paciente del grupo 0.Conclusiones: la inhibición ácida máxima de la secreción ácidagástrica mediante bolo e infusión continua de pantoprazol noofrece resultados superiores al tratamiento con dosis convencionalesen el episodio hemorrágico agudo

Objective: to compare two regimens of pantoprazole administeredintravenously in patients with ulcerative gastrointestinalbleeding (UGB), and a high risk of presenting with persitent or recurrenthemorrhage.Material and method: patients were randomized into twogroups: group 0 - treatment with a 80 mg bolus of pantoprazoleadministered intravenously, followed by continuous infusion of 8mg/h for 72 hours; group 1 - treatment with 40 mg of pantoprazoleadministered intravenously on a daily basis. The percentageof hemorrhagic persistence/recurrence in both groups was analyzed,as were transfusion requirements, need for surgery, andmortality resulting from the hemorrhagic episode.Results: there were 20 patients in group 0 and 21 in group1. No differences were found between groups in terms of gender,age, smoking habits, use of NSAIDs, presence of hemodynamicinstability 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 endoscopictreatment, versus 100% in group 1, p = 0.232. In group0, 50% of patients had a transfusion, as compared to 52.4% ingroup 1, p = 0.879. In group 0, 2 patients (10.5%) presentedwith recurrent hemorrhage, versus 3 patients (14.3%) in group 1.Surgery was required by 1 person from each group, and 1 patientin group 0 died.Conclusions: maximum acid inhibition with a bolus and athen a continuous infusion of pantoprazole does not yield betterresults than treatment with conventional doses in acute hemorrhagicepisodes

Transfusion requirements in patients with gastrointestinal bleeding: a study in a Blood Unit at a referral hospital.

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.

MicroRNA function and mechanism: insights from zebra fish.

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.

Results of an upper endoscopy protocol in liver transplant candidates.

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.

Metástasis intracanalicular de la vía biliar por carcinoma colorrectal como causa de ictericia obstructiva / Intracanalicular metastasis of biliary tract from colorectal carcinoma as cause of obstructive jaundice

No disponible

Anti-ulcer activity and other pharmacological properties of lozilurea.

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.

Influence of plafibride, an antiplatelet and hypolipemic agent, on prostacyclin and thromboxane synthesis, 3',5'-cyclic AMP phosphodiesterase activity and serum clearance of a lipid emulsion.

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.

Pharmacological activities and side effects of plafibride.

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.

3,3-Bis-(4-hydroxyphenyl)-7-methyl-2-indolinone (BHMI), the active metabolite of the laxative sulisatin.

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.