Dual-specificity phosphatase 6 regulates CD4+ T-cell functions and restrains spontaneous colitis in IL-10-deficient mice.

Mitogen-activated protein kinase (MAPK) phosphatases are dual-specificity phosphatases (DUSPs) that dephosphorylate phosphothreonine and phosphotyrosine residues within MAPKs. DUSP6 preferentially dephosphorylates extracellular signal-regulated kinases 1 and 2 (ERK1/2) rendering them inactive. Here, we study the role of DUSP6 in CD4(+) T-cell function, differentiation, and inflammatory profile in the colon. Upon T-cell receptor (TCR) stimulation, DUSP6 knockout (Dusp6(-/-)) CD4(+) T cells showed increased ERK1/2 activation, proliferation, T helper 1 differentiation, and interferon-γ production, as well as a marked decrease in survival, interleukin- 17A (IL-17A) secretion, and regulatory T-cell function. To analyze the role of DUSP6 in vivo, we employed the Il10(-/-) model of colitis and generated Il10(-/-)/Dusp6(-/-) double-knockout mice. Il10(-/-)/Dusp6(-/-) mice suffered from accelerated and exacerbated spontaneous colitis, which was prevented by ERK1/2 inhibition. ERK1/2 inhibition also augmented regulatory T-cell differentiation in vitro and in vivo in both C57Bl/6 and Dusp6(-/-) mice. In summary, DUSP6 regulates CD4(+) T-cell activation and differentiation by inhibiting the TCR-dependent ERK1/2 activation. DUSP6 might therefore be a potential intervention target for limiting aberrant T-cell responses in T-cell-mediated diseases, such as inflammatory bowel disease.

Regulatory role of PI3K-protein kinase B on the release of interleukin-1ß in peritoneal macrophages from the ascites of cirrhotic patients.

Great effort has been paid to identify novel targets for pharmaceutical intervention to control inflammation associated with different diseases. We have studied the effect of signalling inhibitors in the secretion of the proinflammatory and profibrogenic cytokine interleukin (IL)-1ß in monocyte-derived macrophages (M-DM) obtained from the ascites of cirrhotic patients and compared with those obtained from the blood of healthy donors. Peritoneal M-DM were isolated from non-infected ascites of cirrhotic patients and stimulated in vitro with lipopolysaccharide (LPS) and heat-killed Candida albicans in the presence or absence of inhibitors for c-Jun N-terminal kinase (JNK), mitogen-activated protein kinase kinase 1 (MEK1), p38 mitogen-activated protein kinase (MAPK) and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K). The IL1B and CASP1 gene expression were evaluated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The expression of IL-1ß and caspase-1 were determined by Western blot. IL-1ß was also assayed by enzyme-linked immunosorbent assay (ELISA) in cell culture supernatants. Results revealed that MEK1 and JNK inhibition significantly reduced the basal and stimulated IL-1ß secretion, while the p38 MAPK inhibitor had no effect on IL-1ß levels. On the contrary, inhibition of PI3K increased the secretion of IL-1ß from stimulated M-DM. The activating effect of PI3K inhibitor on IL-1ß release was mediated mainly by the enhancement of the intracellular IL-1ß and caspase-1 content release to the extracellular medium and not by increasing the corresponding mRNA and protein expression levels. These data point towards the role of MEK1 and JNK inhibitors, in contrast to the PI3K-protein kinase B inhibitors, as potential therapeutic tools for pharmaceutical intervention to diminish hepatic damage by reducing the inflammatory response mediated by IL-1ß associated with liver failure.

The existence of a relationship between increased serum alanine aminotransferase levels detected in premarketing clinical trials and postmarketing published hepatotoxicity case reports.

BACKGROUND: Drug-induced liver injury (DILI) profile in most drugs' available information is based on both the incidence of alanine aminotansferase (ALT) elevations in clinical trials and published case reports. AIM: To assess the relationship between ALT elevations in clinical trials and the number of published case reports in the postmarketing setting. METHODS: Hepatotoxic drugs were identified from product labelling and classified in high-medium risk (Black Box Warning or Precautions section) or low risk (a statement in the Adverse Reactions section). Incidence of ALT elevations (> or = 3 x ULN) for drug (I(D)) and placebo (I(C)) treated patients in premarketing clinical trials and DILI published case reports were retrieved from product labelling and MEDLINE. RESULTS: The median I(C) was 10/1000. The high-medium-risk drugs' median I(D) was significantly higher compared with low-risk drugs (17/1000 vs. 10/1000; P = 0.046). Chi-squared test, absolute difference and odds ratio comparing I(D) and I(C) identified 35%, 51% and 77% of high-medium-risk drugs respectively. Less number of case reports were associated with low- than high-medium-risk drugs (1 vs. 7; P = 0.001). A high odds ratio in clinical trials (I(D) vs. I(C)) was the strongest predictor of published DILI case reports. CONCLUSION: A relationship between increased ALT incidence in premarketing clinical trials and postmarketing published case reports exists.

Utilización de la ventilación no invasiva en la insuficiencia respiratoria aguda. Estudio multicéntrico en unidades de cuidados intensivos / Use of non-invasive ventilation in acute respiratory failure. Multicenter study in intensive care units

Objetivo. Estudiar el uso de la ventilación no invasiva (VNI) en la insuficiencia respiratoria aguda, en las unidades de cuidados intensivos (UCI) de España. Métodos. Se realizó una encuesta a 254 UCI. Al final de ésta se invitó a participar en un estudio multicéntrico retrospectivo, y proporcionar información detallada sobre pacientes ventilados. Resultados. Contestaron 123 UCI; 119 utilizaban la VNI, de manera muy variable. En la enfermedad pulmonar obstructiva crónica (EPOC), la VNI fue de primera elección en el 89% de las unidades; en el edema agudo de pulmón (EAP), el 79%; en la insuficiencia respiratoria tras la extubación, el 53%; en la neumonía, el 53%, y en el síndrome de distrés respiratorio agudo (SDRA), el 17%. Su utilización en la EPOC fue ocasional o nula en el 11% de las unidades, y en el EAP, en el 21%. 18 hospitales enviaron información de 432 pacientes ventilados, de los que 232 (54%) recibieron VNI como primera elección. La neumonía o el SDRA fueron factores independientes en relación con el fracaso de la VNI (odds ratio ajustada [ORa] = 5,71; intervalo de confianza [IC] del 95%, 1,83-17,8; p = 0,003). La admisión en una unidad que ventilara de forma no invasiva a más de 50 pacientes/año (ORa = 0,22; IC del 95%, 0,07-0,63; p = 0,005) y una mayor razón PaO2/FIO2 tras una hora de ventilación (ORa = 0,98 por punto; IC del 95%, 0,97-0,99; p < 0,001) fueron factores protectores. Conclusiones. La VNI es ampliamente utilizada en las UCI de España, pero es posible que siga estando infrautilizada en la EPOC y el EAP. El diagnóstico de neumonía o SDRA fue un factor independiente en relación con el fracaso. Ventilar a más de 50 pacientes/año y una mayor PaO2/FIO2 tras una hora fueron factores protectores(AU)

Objectives. Study the use of non-invasive ventilation (NIV) in patients with acute respiratory failure in intensive care units (ICUs) in Spain. Methods. A questionnaire was sent to 254 ICUs, after which, they were invited to participate in a multicenter, retrospective study, providing detailed information on ventilated patients. Results. Answers were received from 123 hospitals. Of these, 119 used NIV, although its use varied greatly. NIV is the treatment of choice in 89% of the units for chronic obstructive pulmonary disease (COPD), in 79% for acute pulmonary edema (APE), in 53% for postextubation failure, in 53% for pneumonia 53%, and in 17% for acute respiratory distress syndrome (ARDS). It was used occasionally in COPD in 11% of the units, and in 21% of the units for APE. Eighteen hospitals provided additional information on 432 ventilated patients, 232 (54%) of whom received NIV as first line therapy. Presence of pneumonia or acute respiratory distress syndrome (ARDS) was an independent predictive factor of NIV failure (ORa = 5.71; CI 95%, 1.83-17.8; p = 0.003). Admission in a unit with experience in NIV in > 50 patients/year (ORa = 0.22; CI 95%, 0.07-0.63; p = 0.005) and a higher PaO2/FiO2 ratio after one hour of ventilation (ORa = 0.98 per point; CI 95%, 0.97-0.99; p < 0.001) were protector factors. Conclusions. In Spain, NIV is widely used but it may continue to be underused in COPD and APE. The diagnosis of pneumonia or ARDS was an independent predictive risk factor. Admission in an ICU with NIV in more than 50 patients/year also have higher PaO2/FiO2 ratio after one hour of ventilation were predictive factors of success(AU)

[Bacterial DNA in patients with cirrhosis and sterile ascites. Its role as a marker of bacterial translocation and prognostic tool]. / ADN bacterano en pacientes con cirrosis y ascitis estéril. Papel como marcador de translocación bacteriana y herramienta pronóstica.

During the last decade, we have witnessed an increase in the amount of data related with the presence of bacterial translocation in experimental models of cirrhosis. However, clinical studies have been limited by the lack of non-invasive methods to study this phenomenon. Over the past years, the research developed in our laboratory has been focused on the detection of bacterial DNA in serum and ascitic fluid of patients with cirrhosis and sterile ascites, the clinical and immunological implications of such finding. Initially, by means of a polymerase chain reaction (PCR)-based method and automated nucleotide sequencing, we were able to detect and identify the presence of fragments of bacterial DNA in the mentioned patients with culture-negative, non-neutrocytic ascites. Since then, we have accumulated a core of data suggesting that the presence of bacterial DNA may have an important role not only as a marker of bacterial translocation, but also as a short-term prognostic factor. Here, we discuss the past, present and future of this line of investigation.

ADN bacteriano en pacientes con cirrosis y ascitis estéril. Papel como marcador de translocación bacteriana y herramienta pronóstica / Bacterial DNA in patients with cirrhosis and sterile ascites. Its role as a marker of bacterial translocation and prognostic tool

Durante la última década hemos presenciado un aumento de lacantidad de datos relativos a la presencia de translocación bacterianaen los modelos experimentales de cirrosis. Sin embargo, losestudios clínicos se han visto limitados por la falta de métodos noinvasivos para estudiar dicho fenómeno. En los últimos años, lasinvestigaciones realizadas en nuestro laboratorio se han centradoen la detección del ADN bacteriano en el suero y el líquido ascíticode los pacientes con cirrosis y ascitis estéril, y en las implicacionesclínicas que ello conlleva. Al principio, gracias a un métodobasado en la reacción en cadena de la polimerasa (PCR) y el secuenciamientoautomatizado de nucleótidos, pudimos detectar eidentificar la presencia de fragmentos de ADN bacteriano en dichospacientes con ascitis no neutrocítica y con cultivo negativo.Desde entonces hemos acumulado una serie de datos que indicanque la presencia de ADN bacteriano podría desempeñar un papelimportante no sólo como marcador de translocación bacteriana,sino también como factor pronóstico a corto plazo. Expondremosaquí el pasado, el presente y el futuro de esta línea de investigación

During the last decade, we have witnessed an increase in theamount of data related with the presence of bacterial translocationin experimental models of cirrhosis. However, clinical studies havebeen limited by the lack of non-invasive methods to study this phenomenon.Over the past years, the research developed in our laboratoryhas been focused on the detection of bacterial DNA inserum and ascitic fluid of patients with cirrhosis and sterile ascites,the clinical and immunological implications of such finding. Initially,by means of a polymerase chain reaction (PCR)-based methodand automated nucleotide sequencing, we were able to detect andidentify the presence of fragments of bacterial DNA in the mentionedpatients with culture-negative, non-neutrocytic ascites.Since then, we have accumulated a core of data suggesting thatthe presence of bacterial DNA may have an important role notonly as a marker of bacterial translocation, but also as a shorttermprognostic factor. Here, we discuss the past, present and futureof this line of investigation

Translocation of bacterial DNA from Gram-positive microorganisms is associated with a species-specific inflammatory response in serum and ascitic fluid of patients with cirrhosis.

Translocation of bacterial-DNA in patients with cirrhosis and ascites triggers an innate immune response. Identification of characteristics to which this response is sensitive is relevant from a clinical standpoint. The aim of this study has been to determine if the proinflammatory immune response established in vivo in cirrhotic patients with ascites as a consequence of bacterial-DNA translocation is related to the identified bacterial species and their frequency of cytosine-guanosine content in serum and ascitic fluid. Patients with advanced cirrhosis and ascites were included in the study and distributed into groups I and II according to the absence or presence of bacterial-DNA translocation, respectively. Serum and ascitic fluid levels of proinflammatory cytokines after normalization of bacterial-DNA concentration and the activated form of nuclear factor-kappa B in ascitic fluid pellets were measured by enzyme-linked immunosorbent assay techniques. Translocation of bacterial-DNA with higher cytosine-guanosine content induced the highest cytokine response, which was higher than that in patients without bacterial-DNA translocation. The activated form of nuclear factor-kappa B in ascitic fluid pellets of patients with bacterial-DNA translocation was greater in patients with higher bacterial-DNA cytosine-guanosine content, whereas the amount of total nuclear factor-kappa B remained unaltered. Bacterial-DNA translocation induces a marked immune reaction in vivo in patients with advanced cirrhosis and ascites which is related, among other factors, to the bacterial-DNA cytosine-guanosine content. Therefore, the host's immune response to bacterial-DNA translocation constitutes a species-specific phenomenon.

[ST segment elevation acute coronary syndrome during pregnancy: a case report and review of therapeutic options]. / Síndrome coronario agudo con elevación de ST durante el embarazo: descripción de un caso y revisión de las opciones terapéuticas.

ST segment elevation acute coronary syndrome is a clinical condition that is rarely observed in pregnant women. However, its manifestation is a situation of high maternal-fetal risk. Pharmacotherapeutical management of these patients is difficult and requires individualized care by a multidisciplinary team since many of the standard treatments are included within the categories of teratogencity C or D of the Food and Drug Administration and experience with techniques such as coronary angioplasty with stent placement is scarce. The case of a 32-year woman who was 11 weeks pregnant and diagnosed of acute coronary syndrome with ST segment and its therapeutic approach are described. Furthermore, the information available on epidemiology, etiology and pathophysiology of acute coronary syndrome with ST segment during pregnancy and the specific role of the currently available treatment options are reviewed.

A comparison of two different dosages of somatostatin combined with sclerotherapy for the treatment of acute esophageal variceal bleeding: a prospective randomized trial.

BACKGROUND: the association of somatostatin (SMT) with endoscopic therapy in patients with cirrhosis and variceal bleeding significantly improves the control of the bleeding episode, and hemodynamic data have shown that a dosage of 500 mg/h allows a more marked reduction of portal pressure versus the usual dosage of 250 mg/h. AIM: to assess if the 500 mg/h dosage is associated with an improved outcome. METHODS: sixty-two patients with variceal bleeding were included in the study. Patients were randomized to receive the usual dosage of SMT (group I: 250 mg/h), or a double dosage (group II: 500 mg/h), together with emergency endoscopic sclerotherapy. RESULTS: the control of the bleeding episode was similar in both groups of patients. Early rebleeding was less frequent in patients receiving double vs. single dosage of SMT (p = 0.06). When considering patients with advanced liver disease (Child-Pugh B or C) early rebleeding was significantly less frequent in patients receiving the 500 mg/h dose of SMT (39 vs. 13%, p = 0.03). CONCLUSIONS: the perfusion of higher doses of SMT (500 mg/h) in association with emergency sclerotherapy in patients with cirrhosis and esophageal hemorrhage significantly decreases the rate of early rebleeding in patients with more advanced stages of liver disease.

Functional status of beta-2-adrenoceptor in isolated membranes of mature erythrocytes from patients with cirrhosis and oesophageal varices.

Propranolol is a widely used drug for prophylaxis of variceal bleeding in patients with cirrhosis, but not all patients show an adequate clinical response. This variability may be in relation to beta adrenoceptor activity, but no information is available in this setting. Thirty-nine patients with advanced cirrhosis and presence of oesophageal varices were sequentially included. We studied the function of beta-2-adrenoceptor in isolated membranes of mature erythrocytes obtained from patients by measuring cyclic AMP (cAMP) production before and after isoproterenol. Blood samples obtained from 11 healthy volunteers were used as control. Patients showed a six-fold increase in the mean basal cAMP production as compared to healthy volunteers. Isoproterenol produced a small, non-significantly and highly variable increase in the AC activity in patients compared with controls. cAMP values remain stable after three months of continuous treatment with oral beta-blockers in both groups. Patients without antecedent of variceal bleeding or with an active alcohol intake showed a significantly higher isoproterenol effect. In conclusion, beta-receptor function in human erythrocytes membranes is altered in patients with cirrhosis and oesophageal varices.

A comparison of two different dosages of somatostatin combined with sclerotherapy for the treatment of acute esophageal variceal bleeding: a prospective randomized trial

No disponible

Background: the association of somatostatin (SMT) with endoscopictherapy in patients with cirrhosis and variceal bleedingsignificantly improves the control of the bleeding episode, and hemodynamicdata have shown that a dosage of 500 µg/h allows amore marked reduction of portal pressure versus the usual dosageof 250 µg/h.Aim: to assess if the 500 µg/h dosage is associated with animproved outcome.Methods: sixty-two patients with variceal bleeding were includedin the study. Patients were randomized to receive the usualdosage of SMT (group I: 250 µg/h), or a double dosage (group II:500 µg/h), together with emergency endoscopic sclerotherapy.Results: the control of the bleeding episode was similar inboth groups of patients. Early rebleeding was less frequent in patientsreceiving double vs. single dosage of SMT (p = 0.06). Whenconsidering patients with advanced liver disease (Child-Pugh B orC) early rebleeding was significantly less frequent in patients receivingthe 500 µg/h dose of SMT (39 vs. 13%, p = 0.03).Conclusions: the perfusion of higher doses of SMT (500µg/h) in association with emergency sclerotherapy in patientswith cirrhosis and esophageal hemorrhage significantly decreasesthe rate of early rebleeding in patients with more advanced stagesof liver disease

Detection and identification of bacterial DNA in serum from patients with acute pancreatitis.

BACKGROUND AND AIMS: Bacterial infections are common complications in patients with acute pancreatitis, and translocation of bacteria from the intestinal lumen is probably the first step in the pathogenesis of these infections. As blood cultures in afebrile patients are usually negative, more sensitive methods to investigate this hypothesis in patients are needed. Our group has recently developed a method to detect the presence of bacterial DNA in biological fluids, and we aimed to detect bacterial DNA in patients with acute pancreatitis, as molecular evidences of bacterial translocation. METHODS: Samples of blood were obtained on three consecutive days within the first six days after admission. Bacterial DNA was detected using a polymerase chain reaction based method, and an automated DNA nucleotide sequencing process allowed identification of bacteria species. RESULTS: Thirty one consecutively admitted patients with acute pancreatitis were studied. Bacterial DNA was detected in six patients (19.3%), and the sequencing process allowed identification of Citrobacter freundii and Pseudomonas aeruginosa. In two patients the same bacteria detected at admission was detected 24 hours later (above 99.9% homology of nucleotide sequence). Basic clinical and biochemical characteristics were similar among patients with or without the presence of bacterial DNA. CONCLUSION: Detection of gram negative bacteria derived bacterial DNA in our series supports the contention that bacterial translocation is a systemic process in approximately 20% of patients with acute pancreatitis that does not seem to be related to the severity of the episode or immediate development of infection.

Norfloxacin decreases bacterial adherence of quinolone-resistant strains of Escherichia coli isolated from patients with cirrhosis.

BACKGROUND: Long-term administration of norfloxacin is recommended for secondary prophylaxis of spontaneous bacterial peritonitis in cirrhosis, but it may be associated with the development of quinolone-resistant bacteria in stools. However, these bacteria rarely cause infections. AIM: To assess bacterial adherence of either quinolone-sensitive or -resistant Escherichia coli obtained from stools of cirrhotic patients, as one of the main virulence factors, and its variations when sub-minimum inhibitory concentration of norfloxacin were added to the medium. METHODS: E. coli strains were co-cultured with oral epithelial cells obtained from patients in presence/absence of norfloxacin. Bacterial adherence was measured as percentage of cells exhibiting positive adherence and the number of bacteria attached to epithelial cells. RESULTS: 37 sensitive and 22 resistant E. coli strains were studied. Bacterial adherence was similar in both series (78% vs. 81%, P = N.S.), and these percentages were similarly and significantly reduced when subminimum inhibitory concentration of norfloxacin was added to the culture medium (P < 0.001). CONCLUSIONS: Bacterial adherence of E. coli obtained from patients with cirrhosis is unrelated to the sensitivity/resistance to quinolones, and is similarly reduced in both cases when subminimum inhibitory concentration of norfloxacin is added to the medium.

Pharmacokinetic variations of acetaminophen according to liver dysfunction and portal hypertension status.

AIM: To study the pharmacokinetic and metabolism profiles of a single dose of acetaminophen in patients with cirrhosis. METHODS: Oral acetaminophen (1000 mg) was administered to seven healthy subjects and 14 patients with cirrhosis (nine Child-Pugh A or B and five Child-Pugh C grade), being five without and nine with oesophageal varices. Plasma levels of acetaminophen and its metabolites were determined by HPLC. RESULTS: Patients showed a higher mean area under the curve concentration-time (67.4 +/- 22.4 mg h/L vs. 38.8 +/- 4.3 mg h/L; P = 0.01), a lower clearance (166.7 +/- 85.0 mL/min vs. 367.8 +/- 62.5 mL/min; P = 0.01) and higher elimination half-life (3.8 +/- 1.1 h vs. 2.0 +/- 0.4 h; P = 0.01) of acetaminophen than healthy volunteers. The appearance in blood and the urinary excretion of metabolites in patients did not differ from healthy subjects. Absorption profile was faster in patients. Patients with lower mean and systolic arterial pressure had lower AUC of acetaminophen, independently of liver dysfunction stage. CONCLUSIONS: Patients with cirrhosis had a higher AUC and lower clearance of acetaminophen. Acetaminophen attained earlier therapeutic concentrations in patients with oesophageal varices. Mean and systolic arterial pressures were significantly associated with AUC suggesting the importance of the haemodynamic function on the pharmacokinetics of acetaminophen in patients with cirrhosis.

Bacterial DNA activates cell mediated immune response and nitric oxide overproduction in peritoneal macrophages from patients with cirrhosis and ascites.

BACKGROUND AND AIMS: Translocation of intestinal bacteria to ascitic fluid is probably the first step in the development of episodes of spontaneous bacterial peritonitis in patients with cirrhosis. We have recently reported the detection of bacterial DNA in blood and ascitic fluid from patients with advanced cirrhosis, what we consider as molecular evidence of bacterial translocation. Several studies have shown the immunogenic role of bacterial DNA in vitro, and we hypothesised that the presence of bacterial DNA could activate the type I immune response in peritoneal macrophages from these patients, leading to greater cytokine synthesis (interleukin (IL)-2 and IL-12, tumour necrosis factor alpha, and interferon gamma) and effector molecules such as nitric oxide. METHODS: Peritoneal macrophages obtained from patients with cirrhosis and culture negative non-neutrocytic ascitic fluid were collected and characterised by flow cytometry. Inducible nitric oxide synthase, nitric oxide levels, and cytokine production were measured by immunoenzymometric assays in basal and harvested conditions according to the presence/absence of bacterial DNA. RESULTS: The ability of peritoneal macrophages to synthesise nitric oxide and levels of all cytokines were significantly increased in patients with bacterial DNA. There was a positive correlation between inducible nitric oxide synthase and nitric oxide levels. CONCLUSIONS: The presence of bacterial DNA in patients with decompensated cirrhosis is associated with marked activation of peritoneal macrophages, as evidenced by nitric oxide synthesising ability, together with enhanced cytokine production.

[Etiology of upper gastrointestinal bleeding of peptic origin: role of Helicobacter pylori and NSAIDs]. / Etiología de la hemorragia digestiva alta de origen péptico: papel de Helicobacter pylori y los antiinflamatorios no esteroideos.

INTRODUCTION: Upper gastrointestinal bleeding continues to be a severe and frequent complication in ulcerative disease. Etiologic diagnosis in these patients is highly important in order to initiate appropriate treatment and prevent bleeding recurrence. OBJECTIVE: 1. To investigate the prevalence of Helicobacter pylori infection and use of NSAIDs in patients with upper gastrointestinal hemorrhage of peptic origin. 2. To analyze the strategy used for the diagnosis of H. pylori in our previous work. PATIENTS AND MEHTODS: Seventy-three patients with endoscopically-diagnosed upper gastrointestinal bleeding of peptic origin were included in the study. The use of NSAIDs was investigated. H. pylori infection was diagnosed if one of the following tests was positive: urease test, histology, breath test. RESULTS: H. pylori infection was found in 92% of duodenal ulcers and in 88% of gastric ulcers. Fifty-six percent of the patients had taken NSAIDs. Excluding these patients resulted in an H. pylori infection rate of 96.7%. The diagnosis was based on urease test in 46%. In the remaining patients, breath test and histology were required. CONCLUSIONS: The main etiology in patients with upper gastrointestinal bleeding of peptic origin is H. pylori infection followed by the use of NSAIDs, and these two factors frequently coexist. The strategy of performing a urease test and, when this is negative, performing histological study and a breath test, is valid and allows a diagnosis of H. pylori infection to be made even if patients are receiving treatment that could make diagnosis difficult.

[Toxic hepatitis associated with tamoxifen use. A case report and literature review]. / Hepatitis tóxica asociada al uso de tamoxifeno. Presentación de un caso y revisión bibliográfica.

Tamoxifen is an antiestrogenic drug that acts by binding to the estrogen receptor. The drug is used as a co-adjuvant treatment in advanced breast cancer expressing the oestrogen-receptor protein. Clinical trials of tamoxifen have shown its efficacy in reducing mortality and recurrence rates over a five-year treatment. Cases of tamoxifen-associated hepatotoxicity have been described, including cholestasis with or without cytolysis and steatohepatitis. We report the case of a female patient who developed hepatic alterations while undergoing continuous tamoxifen treatment. We also present an overview of similar cases published to date and comment on the advisability of continuing or suppressing this treatment in patients with hepatotoxicity or after a five-year treatment period.