Management of adverse events from the treatment of encorafenib plus cetuximab for patients with BRAF V600E-mutant metastatic colorectal cancer: insights from the BEACON CRC study.

Colorectal cancer is the second leading cause of cancer deaths worldwide, with a 5-year relative survival of 14% in patients with metastatic colorectal cancer (mCRC). Patients with BRAF V600E mutations, which occur in ∼10%-15% of patients with mCRC, have a poorer prognosis compared with those with wild-type BRAF tumours. The combination of the BRAF inhibitor encorafenib with the epidermal growth factor receptor inhibitor cetuximab currently represents the only chemotherapy-free targeted therapy approved in the USA and Europe for previously treated patients with BRAF V600E-mutated mCRC. As a class, BRAF inhibitors are associated with dermatologic, gastrointestinal, and renal events, as well as pyrexia and secondary skin malignancies. Adverse event (AE) profiles of specific BRAF inhibitors vary, however, and are affected by the specific agents given in combination. In patients with mCRC, commonly reported AEs of cetuximab monotherapy include infusion reactions and dermatologic toxicities. Data from the phase III BEACON CRC study indicate that the combination of encorafenib with cetuximab has a distinct safety profile. Here we review the most frequently reported AEs that occurred with this combination in BEACON CRC and best practices for managing and mitigating AEs that require more than standard supportive care.

Physiological expression of pancreatic somatostatin receptors in 99mTc-HYNIC-TOC scintigraphy.

PURPOSE: To describe the frequency of head and/or pancreas uncinate process uptake of 99mTc-HYNIC-TOC, to study its nature, and analyze its diagnostic value. MATERIALS AND METHODS: Retrospective evaluation of 47 consecutive 99mTc-HYNIC-TOC examinations was conducted. Head and/or pancreas uncinate process uptake was considered to be physiological in patients with normal CT at the same episode and in follow-up. It was analyzed if age or diabetes mellitus was justifying the existence or not of uptake. RESULTS: 32.5% patients showed uptake; 73% of them were mild. 84.6% patients with uptake have no pathology and 4% had neuroendocrine pancreatic disease at CT. Neither the age nor the diabetes mellitus established differences in patients without lesion. CONCLUSIONS: Near one-third of patients show physiological uptake by head and/or pancreas uncinate process at 99mTc-HYNIC-TOC scintigraphy. It seems that neither the diabetes nor the ages are factors that determine this physiological uptake.

Early ovarian follicular development in prepubertal Wistar rats acutely exposed to androgens.

Androgens may directly modulate early ovarian follicular development in preantral stages and androgen excess before puberty may disrupt this physiological process. Therefore, the aim of this study was to investigate the dynamics of follicular morphology and circulating androgen and estradiol levels in prepubertal Wistar rats acutely exposed to androgens. Prepubertal female Wistar rats were distributed into three groups: control, equine chorionic gonadotropin (eCG) intervention and eCG plus dehydroepiandrosterone (DHEA) intervention (eCG+DHEA). Serum DHEA, testosterone and estradiol levels were determined, and ovarian morphology and morphometry were assessed. The eCG+DHEA group presented increased serum estradiol and testosterone levels as compared with the control group (P<0.01), and higher serum DHEA concentration v. the eCG-only and control groups (P<0.01). In addition, the eCG+DHEA group had a higher number of, and larger-sized, primary and secondary follicles as compared with the control group (P<0.05). The eCG group presented intermediate values for number and size of primary and secondary follicles, without significant differences as compared with the other two groups. The number of antral follicles was higher in the eCG+DHEA and eCG groups v. controls (P<0.05). The number of primordial, atretic and cystic follicles were similar in all groups. In conclusion, the present experimental model using an acute eCG+DHEA intervention was useful to investigate events involved in initial follicular development under hyperandrogenic conditions, and could provide a reliable tool to study defective follicular development with possible deleterious reproductive consequences later in life.

Hepatotoxicidad: patrón colestásico inducido por fármacos / Hepatotoxicity: A Drug-Induced Cholestatic Pattern

La enfermedad hepática inducida por fármacos (DILI) es una condición poco frecuente; sin embargo, explica el 40%-50% de las insuficiencias hepáticas agudas. Su patrón es colestásico en un 20%-40%, causado por la inhibición de los transportadores que regulan la síntesis biliar; esta reducción en la actividad es mediada directa o indirectamente por los medicamentos y sus metabolitos, por polimorfismos genéticos y otros factores de riesgo del paciente. Sus manifestaciones van desde las alteraciones bioquímicas en ausencia de síntomas, hasta la insuficiencia hepática aguda y el daño hepático crónico. Aunque no existe un examen o marcador que indique el diagnóstico absoluto de la enfermedad, se han desarrollado escalas y algoritmos que permiten valorar la probabilidad de DILI colestásica, y otras pruebas que por su complejidad y costo no son de uso rutinario. Por lo anterior, es principalmente un diagnóstico de exclusión basado en evidencia circunstancial. El patrón colestásico de DILI presenta una mejor tasa de supervivencia general pero un mayor riesgo de desarrollo de enfermedad hepática crónica. En la mayoría de los casos, el cuadro del paciente mejora con el retiro del medicamento responsable del daño; la hemodiálisis y el trasplante deben considerarse solo para casos selectos. No se ha probado la eficacia de otras terapias. En este artículo se profundizará en la fisiopatología, la presentación clínica, bioquímica e histopatológica, además del diagnóstico, manejo y pronóstico de este tipo de colestasis.

Although drug induced liver disease is a rare condition, it explains 40% to 50% of all cases of acute liver failure. In 20% to 40% of the cases, the pattern is cholestatic and is caused by inhibition of the transporters that regulate bile synthesis. This reduction in activity is directly or indirectly mediated by drugs and their metabolites and/or by genetic polymorphisms and other risk factors of the patient. Its manifestations range from biochemical alterations in the absence of symptoms to acute liver failure and chronic liver damage. Although there is no absolute test or marker for diagnosis of this disease, scales and algorithms have been developed to assess the likelihood of cholestatic drug induced liver disease. Other types of evidence are not routinely used because of their complexity and cost. Diagnosis is primarily based on exclusion using circumstantial evidence. Cholestatic drug induced liver disease has better overall survival rates than other patters, but there are higher risks of developing chronic liver disease. In most cases, the patient’s condition improves when the drug responsible for the damage is removed. Hemodialysis and transplantation should be considered only for selected cases. The effectiveness of other therapies is unproven. This article will delve into the pathophysiology, biochemistry, and histopathology and the clinical presentation of the disease and will discuss diagnosis, management and prognosis of this type of cholestasis.

Leishmaniasis cutánea y anfotericina B liposomal: Reporte de caso / Cutaneous leishmaniasis and liposomal amphotericin B: Case report

La leishmaniasis cutánea es una zoonosis producida por diferentes especies del parásito del género Leishmania . Existen 2 tipos de leishmaniasis, la que se conoce como del nuevo mundo y la del viejo mundo, que son causadas por diferentes especies. La forma de leishmaniasis más común en nuestro medio es la cutánea, rara vez con compromiso sistémico aun en pacientes HIV positivos. El tratamiento consiste en Glucantime, alternativamente miltefosine, los cuales tienen una toxicidad signifi cativa y pueden fallar en un número sustancial de casos. La opción de tratamiento para estos pacientes es la anfotericina B, de las cuales la forma liposomal tiene menor toxicidad renal pero un alto costo y difi cultades para su disponibilidad. Se reporta el caso de un paciente con enfermedad renal crónica y leishmaniasis cutánea, en quien estaba contraindicado el Glucantime y presentó falla terapéutica con miltefosine. Recibió tratamiento con anfotericina B liposomal en una dosis única de 15 mg/kg con adecuada tolerancia, deterioro no signifi cativo de la función renal y resolución de las lesiones cutáneas hasta los 30 y 60 días de seguimiento.

Cutaneous leishmaniasis is a zoonosis caused by various species of Leishmania parasite. There are two types, known as New World and Old World leishmaniasis, which are caused by different species. The most common form of leishmaniasis in our area is mucocutaneous, which rarely has systemic involvement, even in HIV-positive patients. Glucantime is the first choice of therapy, or alternatively miltefosine, both of which have significant toxicity and can fail in a substantial number of cases. The alternative choice of treatment for these patients is amphotericin B, from which the liposomal form has less renal toxicity but a high cost and low availability. We report the case of a patient with chronic renal disease and cutaneous leishmaniasis, in whom Glucantime was contraindicated and therapeutic failure with miltefosine occurred. He was treated with liposomal amphotericin B in a single dose of 15mg/kg with adequate tolerance, no significant deterioration of renal function and resolution of skin lesions after 30 and 60 days of follow up.

Meningitis de Mollaret: reporte de caso / Mollaret´s meningitis: A case report

La meningitis de Mollaret es una enfermedad rara caracterizada por episodios recurrentes y autolimitados de meningitis linfocítica. Se presenta un caso de meningitis de Mollaret asociado a la infección por herpes simple tipo 2 en una mujer de 27 años con confirmación por reacción en cadena de la polimerasa (PCR) del líquido cefalorraquídeo y se hace una revisión del tema.

Mollaret´s meningitis is a rare disease characterized by recurrent and self-limited episodes of lymphocytic meningitis. We present a case of a 27-year-old woman with Mollaret´s meningitis related to viral infection with herpes simplex virus type 2 confirmed by cerebrospinal fluid polymerase chain reaction ( PCR ).

Factores del pronóstico en periodoncia / Periodontal prognosis factors

La asignación del pronóstico se ha hecho durante muchísimo tiempo de manera subjetiva según la opinión del experto tratante; porque aunque los textos clásicos suelen nombrar un conjunto de variables que influencian el pronóstico, cada lector según su experiencia personal interpreta y le da valor diferente a cada una de ellas. En esta revisión se pretende mostrar la evidencia disponible que permite valorar de manera más objetiva el peso de cada variable a la hora de asignar el pronóstico. Las variables sistémicas como la diabetes poco controlada y el tabaquismo pesado, así como factores locales como los niveles de bacterias específicas y parámetros clínicos como sangrado al sondaje, profundidad sondeable, nivel de inserción, pérdida ósea e índice de placa tienen buen nivel de evidencia como predictores de la progresión de la enfermedad periodontal si se analizan combinadamente en un modelo multifactorial. Otros factores sistémicos, tales como el genotipo inmunológico de Interleukina 1, la osteoporosis y otros factores psicosociales como el estrés y el nivel socioeconómico y cultural son poco concluyentes y requiere el diseño de otros estudios.

Evaluación de los enfoques terapéuticos para las varias formas de enfermedad periodontal. Parte II: aspectos microbiológicos / Evaluation of the therapeutic approach for various types of periodontal disease. Part II: Microbiological aspects

Introducción: (ver parte I:) El estudio se inició con 69 pacientes, de los cuales terminaron 55. Métodos: se realizó evaluación al comienzo, a los 3, 6, 12 y 24 meses, de las características sociodemográficas (edad, género, tabaquismo y agrupación familiar) y de los parámetros clínicos (profundidad sondeable, nivel de inserción, sangrado superficial, sangrado al sondaje y microflora subgingival). Se tomaron muestras microbiológicas de 6 sitios al inicio, 12 y 18 meses. En el análisis estadístico se utilizó la prueba Chi cuadrado y la t-student para comparar los promedios en el tiempo, ambos con un nivel de significancia del 5 por ciento. Se realizó análisis de regresión logística para buscar variables predictoras de la respuesta al tratamiento. Los objetivos de la presente investigación fueron determinar la composición microbiana de las bolsas periodontales y evaluar la respuesta de los pacientes malos respondedores a una segunda terapia alternativa con antimicrobianos sistémicos, dos años después de aplicarla y compararla con la de los buenos respondedores. Resultados: tres meses después del tratamiento, los cambios (pérdida o ganancia) en el nivel de inserción (NI), permitieron clasificar a los pacientes en buenos respondedores (BR) a 57 (82,6 por ciento) y malos respondedores (MR) a 12 (17,4 por ciento). Las variables estudiadas no mostraron asociación individual o agrupada con el tipo de respuesta al tratamiento excepto el índice de placa supragingival ≥ 2 (P = 0,05). Conclusiones: el seguimiento a dos años, indica que la terapia alternativa fue beneficiosa para los MR que se comportaron durante este período de igual manera que los BR, ambos mostrando estabilidad en su NI. Las bacterias mas prevalentes fueron: Porphyromonas gingivalis (P. g.), Prevotella intermedia (P. i.), Porphyromonas sp (P.s p.) El 45 por ciento de los pacientes presentaron entéricos y los MR 78 por ciento.

Evaluación de los enfoques terapéuticos para las varias formas de enfermedad periodontal: Parte I: Aspectos clínicos / Evaluation of the therapeutically approach of various types of periodontal disease: Part I: Clinical aspects

El estudio se inició con 69 pacientes, de los cuales terminaron 55. Se realizó evaluación al comienzo, a los 3, 6, 12 y 24 meses, de las características sociodemográficas: edad, género, tabaquismo y agrupación familiar, de los signos y de los parámetros clínicos: profundidad sondeable, nivel de inserción, sangrado superficial, sangrado al sondaje (parte I) y microflora subgingival (parte II), para lo cual se tomaron muestras microbiológicas de 6 sitios al inicio, 12 y 18 meses. En el análisis estadístico se utilizó la prueba Chi cuadrado y la t-student para comparar los promedios en el tiempo, ambos con nivel de significancia del 5 por ciento. Se realizó análisis de regresión logística para buscar variables predictoras de la respuesta al tratamiento. Los objetivos del estudio (parte I) fueron: 1) Identificar cuáles de las variables sociodemográficas, signos de la enfermedad periodontal y de los parámetros clínicos, podrían anticipar la respuesta buena o mala, a la terapia periodontal no quirúrgica tradicional (detartraje y alisado radicular por cuadrantes), tres meses después de aplicarla. 2) Evaluar el comportamiento de los parámetros clínicos durante dos años de seguimiento. Los cambios (pérdida o ganancia) o estabilidad en los niveles de inserción (NI) permitieron clasificar a los 3 meses en buenos respondedores (BR) a 57 pacientes (82.6 por ciento) y malos respondedores (MR) a 12 (17,4 por ciento). Las variables estudiadas no mostraron asociación individual o agrupada con el tipo de respuesta al tratamiento excepto el índice de placa supragingival ≥ 2 (P = 0,05). El seguimiento a dos años indica que la terapia alternativa (detartraje y alisado radicular boca completa complementada con antibiótico sistémico) fue beneficiosa para los MR que se comportaron durante este periodo de igual manera que los BR, ambos mostrando estabilidad en su nivel de inserción.

The study initiated with 69 patients, out of which 55 were available at the completion of the trial. Evaluations were made at the beginning, 3, 6, 12 and 24 months. The initial exam included the following socio demographic criteria: age, gender, tobacco use and family grouping. The clinical criteria included were: probing depth, clinical attachment, superficial bleeding, probing bleeding (Part I) and sub gingival micro flora. (Part II). Microbiological samples were taken from 6 different sites at the beginning. 12 and 18 months. The statistical analysis included the Chi square and Student’s T test for paired averages in time, both with a level of significance of 5%. Also a logistic regression analysis was done to find predictive variables of response to treatment. The objectives of this study (Part I) were: 1) to identify which of the social demographic variables, signs of periodontal disease and clinical parameters could anticipate a good or poor response to non-surgical traditional periodontal therapy (scaling and root planning per quadrant) 3 months after being applied. 2) to evaluate the behavior of clinical parameters after a 2 year follow-up period. Three months after treatment the changes (loss or gain) in clinical attachment (CA) allowed us to classify the patients as: Responsive (R) to 57 patients (82.6%) and Non Responsive (NR) to 12 (17.4%). The variables analyzed did not show individual or group association with the type of response to treatment, with the exception of supra gingival index plaque ≥ 2 (P = 0.05). Follow up after two years indicated that the alternative treatment (scaling and root planning complemented with systemic antibiotics) was beneficial for the NR that behaved during this period in the same way as the R, both showing stability in the CA.

Comportamiento del suicidio de Antioquia 1998-2000 / Suicide behavior in Antioquia 1998-2000

Casi un millón de personas cometen suicidio en un año en todo el mundo. Por lo que hoy en día es considerado como un serio problema de Salud Pública en muchos países. En Colombia y especialmente en nuestro medio no se conoce su real magnitud y los eventos relacionados. Para describir algunas características del suicidio en Antioquia se realizó un estudio descriptivo, a partir de los datos de mortalidad del DANE entre 1998 y 2000. Se encontró un promedio de 310 suicidios al año, para una tasa de 5.9/100.000 personas, siendo más frecuente en junio y diciembre. El 76 por ciento de los casos ocurrieron en hombres, a una edad promedio de 32 años y de 28 años en las mujeres, para ambos grupos el mayor compromiso fue en los menores de 25 años. El 77 por ciento de los suicidios ocurrió en el área urbana, mientras que 40 por ciento de los mismos ocurrieron en el hogar de la persona. En los hombres, los métodos más usados para quitarse la vida fueron las armas de fuego y el ahorcamiento, y en las mujeres lo fueron el envenenamiento y el ahorcamiento. El 54 por ciento de todos los casos se reportaron en 4 municipios del área metropolitana, aunque se observaron importantes diferencias en las tasas de los municipios del Departamento. En conclusión: Se encontró un aumento del número y la tasa de suicidios en Antioquia, especialmente en los jóvenes, lo cual se favorece por la tendencia de armas y la facilidad para la ejecución de venenos en ciertos grupos...

Transmisión sexual del virus de Hepatitis C / Sexual transmision of Hepatitis C virus

Fifty heterosexual partners out of 50 patients (index cases) without confirmed or probable risk factors of parenteral transmission by HCV were studied from 1/1997 to 1/2001. The index cases were HCV Ab (+) (EIA 3rd Abbott and PCR + by RT-nested PCR). The couples with probable or confirmed risk factors of parenteral transmission were strictly excluded. No case of HCV infection was found, suggesting that sexual via wouldn't be a direct transmission of HCV

Displasia broncopulmonar / Bronchopulmonary Dysplasia

La Displasia Broncopulmonar (DBP) es una enfermedad que afecta a los pacientes prematuros, de muy bajo peso al nacer, con deficiencia de surfactante y exposición a oxigenoterapia y/o ventilación mecánica por lo menos con 28 días o más de edad post-natal. Anteriormente la aparición de pulmón en burbuja en la radiografía se consideraba indispensable para el diagnóstico de DBP, en la actualidad, debido a que algunos pacientes pueden permanecer en estadio de edema pulmonar sin llegar a patrón de burbuja, los criterios clínicos e imagenológicos han cambiado. El objetivo de esta revisión es contemplar la definición actual de DBP, su fisiopatología, manifestaciones clínicas, aspectos radiológicos y las complicaciones que presenta

Diagnóstico por imágenes / Imagen diagnostic

Resumen: Paciente de 44 años, casada, sin hijos, vive en Cali, trabaja en labores de oficina. Tiene un diagnóstico de linfoma no Hodking del manto desde hace aproximadamente 14 meses, para lo cual ha recibido quimioterapia y radioterapia en múltiples ocasiones sin una mejoría clara, razón por la cual posteriormente se decidió realizar un trasplante autólogo de médula ósea. Las células fueron colectadas por la maquina de aféresis a partir de células de sangre periférica. En la evaluación pre-trasplante se obtuvieron los siguientes datos: HIV negativo, IgG para citomegalovirus (CMV) y toxoplasma positivos, perfil hepático normal, Hb 11 gr/dl, Hto 32 %,leucograma: 3000 leucocitos/ mm3

Parathyroid hormone induces hepatic production of bioactive interleukin-6 and its soluble receptor.

Interleukin-6 (IL-6) is an important mediator of parathyroid hormone (PTH)-induced bone resorption. Serum levels of IL-6 and its soluble receptor (IL-6sR) are regulated in part by PTH. The PTH/PTH-related protein type 1 receptor is highly expressed in the liver, and in the current study we investigated whether the liver produces IL-6 or IL-6sR in response to PTH. Perfusion of the isolated rat liver with PTH-(1-84) stimulated rapid, dose-dependent production of bioactive IL-6 and the IL-6sR. These effects were observed at near physiological concentrations of the hormone such that 1 pM PTH induced hepatic IL-6 production at a rate of approximately 0.6 ng/min. In vitro, hepatocytes, hepatic endothelial cells, and Kupffer cells, but not hepatic stellate cells, were each found to produce both IL-6 and IL-6sR in response to higher (10 nM) concentrations of PTH. Our data suggest that hepatic-derived IL-6 and IL-6sR contribute to the increase in circulating levels of these cytokines induced by PTH in vivo and raise the possibility that PTH-induced, liver-derived IL-6 may exert endocrine effects on tissues such as bone.

Communication via gap junctions modulates bile secretion in the isolated perfused rat liver.

BACKGROUND & AIMS: Bile secretion is regulated in part by adenosine 3',5'-cyclic monophosphate (cAMP) and cytosolic Ca2+ (Ca2+i). Hormone receptors that link to these second messengers are not uniformly distributed across the hepatic lobule, but both cAMP and Ca2+i cross gap junctions, so we tested whether gap junctional communication plays a role in changes in bile flow induced by the activation of these receptors. METHODS: cAMP levels in isolated perfused rat livers were increased by using glucagon, because glucagon receptors are predominantly on pericentral hepatocytes, or by using dibutyryl cAMP, which acts on hepatocytes throughout the hepatic lobule. Ca2+i concentration was increased by using vasopressin, because V1a receptors are most heavily expressed on pericentral hepatocytes, or by using 2,5-di(tert-butyl)-1, 4-benzo-hydroquinone (t-BuBHQ), which increases the Ca2+i concentration in hepatocytes throughout the hepatic lobule. We used 18alpha-glycyrrhetinic acid (alphaGA) to block gap junction conductance, which was assessed by fluorescence recovery after photobleaching. RESULTS: alphaGA blocked fluorescence recovery after photobleaching without altering the basal rate of bile flow. Glucagon and dibutyryl cAMP increased bile flow; alphaGA blocked the glucagon-induced increase but not that induced by dibutyryl cAMP. Vasopressin and t-BuBHQ decreased bile flow; alphaGA exacerbated the decrease induced by vasopressin but not by t-BuBHQ. CONCLUSIONS: Glucagon and vasopressin modulate bile flow in a manner that depends in part on gap junctional communication, even though the two hormones activate second messengers with opposing effects on bile flow. The organization of second messenger signals across the hepatic lobule may be an important component of hormonal regulation of bile secretion.

Hepatic sequestration and modulation of the canalicular transport of the organic cation, daunorubicin, in the Rat.

In contrast to organic anions, substrates for the canalicular mdr1a and b are usually organic cations and are often sequestered in high concentrations in intracellular acidic compartments. Because many of these compounds are therapeutic agents, we investigated if their sequestration could be regulated. We used isolated perfused rat liver (IPRL), isolated rat hepatocyte couplets (IRHC), and WIF-B cells to study the cellular localization and biliary excretion of the fluorescent cation, daunorubicin (DNR). Despite rapid (within 15 minutes) and efficient (>90%) cellular uptake in the IPRL, only approximately 10% of the dose administered (0.2-20 micromol) was excreted in bile after 85 minutes. Confocal microscopy revealed fluorescence predominantly in vesicles in the pericanalicular region in IPRL, IRHC, and WIF-B cells. Treatment of these cells with chloroquine and bafilomycin A, agents that disrupt the pH gradient across the vesicular membrane, resulted in a loss of vesicular fluorescence, reversible in the case of bafilomycin A. Taurocholate (TC) and dibutyryl cAMP (DBcAMP), stimulators of transcytotic vesicular transport, increased the biliary recovery of DNR significantly above controls, by 70% and 35%, respectively. The microtubule destabilizer, nocodazole, decreased biliary excretion of DNR. No effect on secretion was noted in TR- mutant rats deficient in mrp2. Coadministration of verapamil, an inhibitor of mdr1, also decreased DNR excretion. While TC and DBcAMP did not affect the fluorescent intensity or pattern of distribution in IRHC, nocodazole resulted in redistribution of DNR to peripheral punctuate structures. These findings suggest that the organic cation, DNR, is largely sequestered in cells such as hepatocytes, yet its excretion can still be modulated.

[Hepatocellular carcinoma: clinical and epidemiological characteristics]. / Carcinoma hepatocelular: características clinicoepidemiológicas.

We present 12 patients with CHC, 11 men and one woman, median age, 59.9 +/- 10.1 cared for in two hospitals from La Plata city. The median age, the predominance of men and presence of cirrhosis in the 75% are similar findings to European 41% of the patients, consulted of the CHC has increased in our environment. The fact that all the patients have been symptomatic at the moment of the consultation, that one of them had normal liver function tests and that only two of them had nodule of less than 5 cm of diameter, suggest advanced stage of the disease. At the same time, the median of survival of 8.3 +/- 9 (DS) months post-diagnosis and of 3.6 +/- 8 (DS) months post surgery. 90.9% had a risk factor to undergo CHC (alcohol, HBC, HCV). Because of one patient, the risk of hemodyalizer patients to have CHC is emphasized. Therefore, it is important to prevent and treat viral infections. In this study, the diagnosis of the echography was of 100% and the histologic corroboration was done by percutaneous biopsy with ultrasound or TC assessment. We observed that the levels of alpha-fetoprotein had a weak, negative correlation, not significative, with the diameters of the nodules. Although it is true that the size of the sample and the retrospective character of the investigation inhibits us to draw definitive conclusions, the behaviour of alfafetoprotein creates doubts about its value in the diagnosis and screening of the CHC.

Role of glutathione in hepatic bile formation during reperfusion after cold ischemia of the rat liver.

BACKGROUND/AIMS: Liver reperfusion following cold ischemia is frequently associated with diminished bile flow in patients undergoing liver transplantation. Glutathione is a major determinant of bile-acid independent bile flow, and the effects of cold ischemia on biliary glutathione excretion are unknown. METHODS: We examined the effects of cold ischemia (University of Wisconsin solution (4 degrees C), 24 h) with subsequent reperfusion (100 min) on biliary glutathione excretion in a recirculating system. Since glutathione might represent an important antioxidant within the biliary tract and oxidative stress in the biliary tract during reperfusion could contribute to the pathogenesis of bile duct injury after liver transplantation, we also assessed bile duct morphology in reperfused livers of mutant TR- -rats, in whom biliary excretion of glutathione is already impaired. RESULTS: Hepatic bile formation was diminished in reperfused Wistar rat livers after cold ischemia. Biliary glutathione concentrations and output were significantly decreased and correlated with postischemic changes in bile secretion. An increased biliary oxidized glutathione/glutathione ratio, indicating oxidative stress, was detected only immediately after the onset of reperfusion. Basal bile flow rates in TR- -rat livers which were already markedly reduced in control-perfused livers, decreased further during the early but not the later reperfusion period. Reperfusion of both Wistar and TR- -rat livers was not associated with electron microscopic evidence of bile duct damage. CONCLUSIONS: We conclude that impaired biliary excretion of glutathione contributes to decreased bile flow after cold ischemia. The absence of biliary glutathione does not appear to promote ultrastructural evidence of bile duct injury during reperfusion in the isolated perfused rat liver.