Tractament rehabilitador en pacients amb c��ncer de mama sotmeses a limfadentecomia axil��lar o bi��psia selectiva del gangli sentinella

Introducci��. La cirurgia de c��ncer de mama est�� associada a morbiditat de l���extremitat superior (ES) tribut��ria de prevenci�� i de tractament rehabilitador. Objectius: Identificar la morbiditat de l���ES despr��s de limfadenectomia axil��lar (LA) o bi��psia selectiva del gangli sentinella (BSGS); el moment del diagn��stic i quan ��s tributaria de tractament rehabilitador. Estudiar la relaci�� d���aquesta morbiditat amb variables cl��niques periquir��rgiques. Material i m��todes. Estudi longitudinal descriptiu amb 2 anys seguiment. Es recolliren les variables edat, pes, talla, tipus de tractament quir��rgic, complicacions peri-quir��rgiques, alteracions de l���espatlla, limfedema, dolor neurop��tic, lesions neurol��giques i la indicaci�� de tractament rehabilitador per aquestes alteracions. Les relacions es van estudiar amb t-test o ji quadrat, amb significaci�� p& 0,05 Resultats: Es van incloure 312 pacients. Van requerir tractament rehabilitador 133 (42,6%) pacients, 81 (26,0%) per alteracions de l���espatlla, 63 (20,2%) per limfedema, 21 (6,7%) per dolor neurop��tic, i 9 (2.9%) per esc��pula alada. Es van determinar relacions significatives de limfedema amb LA (p=0.000); les alteracions de l���espatlla amb les complicacions periquir��rgiques (p=0.04); dolor neurop��tic amb edat m��s jove (p=0.004); i l���esc��pula alada amb hematoma (p=0.000). M��s del 70% dels diagn��stics i tractaments de l���espatlla i limfedema es van realitzar durant el primer any de seguiment. Conclusions: Van requerir tractament rehabilitador 42.6% de pacients. Les alteracions de l���espatlla i el limfedema varen ser les m��s freq��entment tractades. La majoria de diagn��stics i tractament s���efectuaren durant el primer any de seguiment.

An��lisis de supervivencia post-trasplante hep��tico por Cirrosis post-hepatitis C en pacientes coinfectados VIH/VHC, en comparaci��n con monoinfectados por VHC.

La TARGA (terapia antirretroviral de gran activitat) ha camviat el pron��stic dels pacients infectats pel VIH. Actualment la cirrosi per VHC y el hepatocarcinoma son les principales causes de mort. El trasplantament hep��tic (TH) es una indicaci�� recent en aquests pacients. Objectius: Comparar la superviv��ncia post-TH en pacients coinfectats VHC/VIH front a monoinfectats VHC. Conclusions: Els resultats preliminars en el nostre centre son inferiors en pacients coinfectats en comparaci�� amb els controls, que podr��a ser degut a contraindicacions para el tractament antiviral i a una menor eficacia del mateix.

Evaluaci��n de la eficacia y seguridad del tratamiento con tetratiomolibdato de amonio en la enfermedad de Wilson con afectaci��n neurol��gica

El tractament actual de la malaltia de Wilson amb afectaci�� neurol��gica ��s controvertit. Els f��rmacs actuals s���associen a risc de deteriorament neurol��gic (50% amb penicilamina i 26% amb trientine). El nou medicament tetratiomolibdat s���est�� estudiant perqu�� sembla tenir menor freq����ncia d���empitjorament neurol��gic. S���associa a efectes secundaris lleus i generalment reversibles. A la nostra s��rie de cinc pacients v��rem observar una milloria significativa dels s��mptomes despr��s del tractament amb tetratiomolibdat. No es va detectar cap empitjorament neurol��gic. En dos casos va haver tamb�� una millora radiol��gica. Un pacient va presentar lleu an��mia, leucop��nia i elevaci�� de les transaminases reversible.

An��lisis del comportamiento de la procalcitonina en el paciente con cirrosis hep��tica ingresado en una unidad de cuidados intensivos

La procalcitonina (PCT) ��s un dels biomarcadors d'inflamaci�� aplicats al camp de la infecci�� m��s estudiats en els ��ltims anys. Es forma en diversos par��nquimes incloent el fetge. Alguns autors van postular que la disfunci�� hep��tica podria ocasionar falsos negatius en la determinaci�� de la procalcitonina. Estudiem la resposta de la PCT en pacients amb insufici��ncia hep��tica, analitzem retrospectivament el seu comportament en els pacients amb cirrosis hep��tica ingressats en la nostra unitat de vigil��ncia intensiva (UVI). Finalment observem que la disfunci�� hep��tica no impedeix l'augment de la PCT. Per tant, segueix sent ��til per identificar infeccions bacterianes

Factors pron��stics de la hepatitis alcoh��lica greu

La hepatitis alcoh��lica (HAA) greu s���associa a una mortalitat preco�� elevada. En els darrers anys s���han identificat nombrosos marcadors cl��nics i anal��tics que permeten valorar el pron��stic de la malaltia i en base als mateixos s���han elaborat diversos ��ndexs pron��stics. L���objectiu del treball va ser identificar els factors pron��stics associats a la mortalitat de l���HAA i avaluar els diferents ��ndexs pron��stics. Aix��, es varen estudiar de forma retrospectiva 66 episodis d���HAA greu que van ingressar a l���Hospital Germans Trias i Pujol de Badalona des de gener del 2000 fins al desembre del 2008.

Parasitisme i condici�� del llu�� (Merluccius merluccius) del Golf de Lle��

El llu�� europeu del Golf de Lle�� ��s una esp��cie amb un gran valor comercial a les llotges catalanes per la qual cosa es troba sobreexplotat. Els par��metres indicadors de la condici�� f��sica avaluen la salut dels peixos i poden ajudar a predir la productivitat de les poblacions explotades. Un factor que pot estar relacionat amb la condici�� ��s el parasitisme, tot i que les investigacions en aquest sentit s��n molt escasses. Aquest estudi avalua per primera vegada la relaci�� entre parasitisme i condici�� del llu�� europeu. S���han examinat 30 individus, entre gener i mar�� de 2010, i s���han localitzat par��sits que s���han classificat com a nematodes, cestodes, cop��podes i trematodes. S���han calculat tamb��, els ��ndexs de condici�� Le Cren, ��ndex hepatosom��tic, ��ndex gonodosom��tic i contingut lip��dic en fetge i g��nades. Els resultats d���aquest estudi suggereixen que els llu��os infectats amb cop��podes tenen una quantitat inferior de l��pids al fetge, la qual cosa podria indicar una menor condici�� f��sica. Malgrat tot, cal disposar de m��s mostres per poder afirmar aquest fet, aix�� com una s��rie temporal de dades que comprengui totes les estacions de l��� any

��ndices predictivos de fibrosis en la detecci��n del h��gado graso no alcoh��lico: utilidad en Atenci��n Primaria.

El h��gado graso no alcoh��lico(HGNA) es una entidad muy prevalente que se asocia con un aumento del riesgo cardiovascular global. Normalmente es asintom��tica. Los ��ndices serol��gicos de fibrosis se est��n investigando para su diagn��stico. Objetivo: analizar la utilidad de los ��ndices HAIR, FLI y LAP para el diagn��stico del HGNA y la concordancia entre ellos. Metodolog��a: estudio descriptivo, poblacional, multic��ntrico realizado en Atenci��n Primaria en sujetos sanos de entre 15-85 a��os. Las prevalencias fueron de HAIR 68,1%, FLI 46,8%, LAP 56%. Concordancia modesta de los ��ndices. Es necesario seguir investigando para encontrar un ��ndice ��til para el diagn��stico.

Milloria de l���aplicabilitat i la fiabilitat diagn��stica de l���elastografia per avaluar la rigidesa hep��tica en les malalties hep��tiques cr��niques

L���elastografia de transici�� (ET) ��s un m��tode no invasiu per avaluar la fibrosi hep��tica. El major problema ��s la baixa aplicabilitat (20% de resultats inadequats), relacionats amb obesitat del pacient i baixa experi��ncia de l���explorador. En aquest estudi es planteja augmentar aplicabilitat i fiabilitat diagn��stica. L���estudi va incloure 868 registres. Amb una segona avaluaci�� per personal experimentat i una tercera amb material espec��fic es van obtenir registres adequats en la majoria dels pr��viament inadequats. La fiabilitat diagn��stica va augmentar a la segona i tercera exploracions. Conclusi��: La revaluaci�� dels registres inadequats permet augmentar aplicabilitat i fiabilitat diagn��stica de la t��cnica.

Hereditary hepatic and systemic amyloidosis caused by a new deletion/insertion mutation in the apolipoprotein AI gene.

We report a Spanish family with autosomal-dominant non-neuropathic hereditary amyloidosis with a unique hepatic presentation and death from liver failure, usually by the sixth decade. The disease is caused by a previously unreported deletion/insertion mutation in exon 4 of the apolipoprotein AI (apoAI) gene encoding loss of residues 60-71 of normal mature apoAI and insertion at that position of two new residues, ValThr. Affected individuals are heterozygous for this mutation and have both normal apoAI and variant molecules bearing one extra positive charge, as predicted from the DNA sequence. The amyloid fibrils are composed exclusively of NH2-terminal fragments of the variant, ending mainly at positions corresponding to residues 83 and 92 in the mature wild-type sequence. Amyloid fibrils derived from the other three known amyloidogenic apoAI variants are also composed of similar NH2-terminal fragments. All known amyloidogenic apoAI variants carry one extra positive charge in this region, suggesting that it may be responsible for their enhanced amyloidogenicity. In addition to causing a new phenotype, this is the first deletion mutation to be described in association with hereditary amyloidosis and it significantly extends the value of the apoAI model for investigation of molecular mechanisms of amyloid fibrillogenesis.

Temporal changes in the expression and distribution of adhesion molecules during liver development and regeneration

We have compared by immunocytochemistry and immunoblotting the expression and distribution of adhesion molecules participating in cell-matrix and cell-cell interactions during embryonic development and regeneration of rat liver. Fibronectin and the fibronectin receptor, integrin alpha 5 beta 1, were distributed pericellularly and expressed at a steady level during development from the 16th day of gestation and in neonate and adult liver. AGp110, a nonintegrin fibronectin receptor was first detected on the 17th day of gestation in a similar, nonpolarized distribution on parenchymal cell surfaces. At that stage of development haemopoiesis is at a peak in rat liver and fibronectin and receptors alpha 5 beta 1 and AGp110 were prominent on the surface of blood cell precursors. During the last 2 d of gestation (20th and 21st day) hepatocytes assembled around lumina. AGp110 was initially depolarized on the surface of these acinar cells but then confined to the lumen and to newly-formed bile canaliculi. At birth, a marked increase occurred in the canalicular expression of AGp110 and in the branching of the canalicular network. Simultaneously, there was enhanced expression of ZO-1, a protein component of tight junctions. On the second day postpartum, presence of AGp110 and of protein constituents of desmosomes and intermediate junctions, DGI and E-cadherin, respectively, was notably enhanced in cellular fractions insoluble in nonionic detergents, presumably signifying linkage of AGp110 with the cytoskeleton and assembly of desmosomal and intermediate junctions. During liver regeneration after partial hepatectomy, AGp110 remained confined to apical surfaces, indicating a preservation of basic polarity in parenchymal cells. A decrease in the extent and continuity of the canalicular network occurred in proliferating parenchyma, starting 24 h after resection in areas close to the terminal afferent blood supply of portal veins and spreading to the rest of the liver within the next 24 h. Distinct acinar structures, similar to the ones in prenatal liver, appeared at 72 h after hepatectomy. Restoration of the normal branching of the biliary tree commenced at 72 h. At 7 d postoperatively acinar formation declined and one-cell-thick hepatic plates, as in normal liver, were observed.

Fsp27/CIDEC is a CREB target gene induced during early fasting in liver and regulated by FA oxidation rate

FSP27 (CIDEC in humans) is a protein associated with lipid droplets that downregulates the fatty acid oxidation (FAO) rate when it is overexpressed. However, little is known about its physiological role in liver. Here, we show that fasting regulates liver expression of Fsp27 in a time-dependent manner. Thus, during the initial stages of fasting a maximal induction of 800-fold was achieved, while during the later phase of fasting, Fsp27 expression decreased. The early response to fasting can be explained by a canonical PKA-CREB-CRTC2 signaling pathway since: i) CIDEC expression was induced by forskolin, ii) Fsp27 promoter activity was increased by CREB, and iii) Fsp27 expression was upregulated in the liver of Sirt1 knockout animals. Interestingly, pharmacological (etomoxir) or genetic (Hmgcs2 interference) inhibition of the FAO rate increases the in vivo expression of Fsp27 during fasting. Similarly, CIDEC expression was upregulated in HepG2 cells by either etomoxir or HMGCS2 interference. Our data indicate that there is a kinetic mechanism of auto-regulation between short- and long-term fasting, by which free fatty acids delivered to the liver during early fasting are accumulated/exported by FSP27/CIDEC, while over longer periods of fasting they are degraded in the mitochondria through the carnitine palmitoyl transferase (CPT) system.

Vascular endothelial growth factor and angiopoietin-2 play a major role in the pathogenesis of vascular leakage in cirrhotic rats.

Background and aims: The extent and molecular mechanisms governing plasma extravasation and formation of ascites in cirrhosis are unknown. Vascular endothelial growth factor-A (VEGF-A) and angiopoietin-2 (Ang-2) are endogenous substances with powerful vascular permeability effects. We assessed regional blood flow, vascular leakage, mRNA and tissular expression of VEGF-A and Ang-2 and vascular permeability following VEGF receptor 2 blockade in control and cirrhotic rats to define the vascular territories showing altered vascular permeability in cirrhosis and to determine whether VEGF-A and Ang-2 are involved in this phenomenon. Methods: Arterial blood flow was analysed with the coloured microsphere method. Vascular leakage was measured and visualised with the dye Evan��s Blue and colloidal carbon techniques, respectively. VEGF-A and Ang-2 expression were determined by real-time polymerase chain reaction (RT-PCR), immunohistochemistry and western blot. The effect on vascular permeability induced by VEGFR2 blockade was assessed by administration of the receptor inhibitor SU11248. Results: Arterial blood flow was increased in the mesentery, pancreas and small intestine but not in the kidney and spleen of cirrhotic rats as compared to controls. Increased vascular leakage was observed in the mesentery and liver, where colloidal carbon spread from microvessels to the adjacent fibrotic tracts. Increased hepatic and mesenteric expression of VEGF-A and Ang-2 was found in cirrhotic rats as compared to controls. Blockade of VEGFR2 markedly reduced hepatic and mesenteric vascular leakage in cirrhotic rats. Conclusions: Enhanced endothelial permeability is restricted to the hepatic and mesenteric vascular beds in cirrhotic rats with ascites and VEGF-A and Ang-2 are key factors in the signalling pathways regulating this dysfunction.

Genetic evidence of heterogeneity in intrahepatic cholestasis of pregnancy

Background and aims: The aim of this study was to investigate the genetic aetiology of intrahepatic cholestasis of pregnancy (ICP) and the impact of known cholestasis genes (BSEP, FIC1, and MDR3) on the development of this disease. Patients and methods: Sixty nine Finnish ICP patients were prospectively interviewed for a family history of ICP, and clinical features were compared in patients with familial ICP (patients with a positive family history, n=11) and sporadic patients (patients with no known family history of ICP, n=58). For molecular genetic analysis, 16 individuals from two independently ascertained Finnish ICP families were genotyped for the flanking markers for BSEP, FIC1, and MDR3. Results: The pedigree structures in 16% (11/69) of patients suggested dominant inheritance. Patients with familial ICP had higher serum aminotransferase levels and a higher recurrence risk (92% v 40%). Both segregation of haplotypes and multipoint linkage analysis excluded BSEP, FIC1, and MDR3 genes in the studied pedigrees. Additionally, the MDR3 gene, previously shown to harbour mutations in ICP patients, was negative for mutations when sequenced in four affected individuals from the two families. Conclusions: These results support the hypothesis that the aetiology of ICP is heterogeneous and that ICP is due to a genetic predisposition in a proportion of patients. The results of molecular genetic analysis further suggest that the previously identified three cholestasis genes are not likely to be implicated in these Finnish ICP families with dominant inheritance.

Effect of chronic ethanol feeding on rat hepatocytic glutathione. Compartmentation, efflux, and response to incubation with ethanol.

Hepatocytes from rats that were fed ethanol chronically for 6-8 wk were found to have a modest decrease in cytosolic GSH (24%) and a marked decrease in mitochondrial GSH (65%) as compared with pair-fed controls. Incubation of hepatocytes from ethanol-fed rats for 4 h in modified Fisher's medium revealed a greater absolute and fractional GSH efflux rate than controls with maintenance of constant cellular GSH, indicating increased net GSH synthesis. Inhibition of gamma-glutamyltransferase had no effect on these results, which indicates that no degradation of GSH had occurred during these studies. Enhanced fractional efflux was also noted in the perfused livers from ethanol-fed rats. Incubation of hepatocytes in medium containing up to 50 mM ethanol had no effect on cellular GSH, accumulation of GSH in the medium, or cell viability. Thus, chronic ethanol feeding causes a modest fall in cytosolic and a marked fall in mitochondrial GSH. Fractional GSH efflux and therefore synthesis are increased under basal conditions by chronic ethanol feeding, whereas the cellular concentration of GSH drops to a lower steady state level. Incubation of hepatocytes with ethanol indicates that it has no direct, acute effect on hepatic GSH homeostasis.

Inhibition of glutathione efflux in the perfused rat liver and isolated hepatocytes by organic anions and bilirubin. Kinetics, sidedness, and molecular forms.

Using isolated, in situ, single-pass perfused rat livers, incubations of freshly isolated hepatocytes, and sinusoidal membrane-enriched vesicles, we and others have shown the saturability of transport (efflux) of hepatic glutathione (GSH). These observations have implicated a carrier mechanism. Our present studies were designed to provide further evidence in support of a carrier mechanism for hepatic GSH efflux by demonstrating competition by liver-specific ligands which are taken up by hepatocytes. Perfusing livers with different substances, we found that: (a) sulfobromophthalein-GSH (BSP-GSH) had a dose-dependent and fully reversible inhibitory effect on GSH efflux, while GSH alone did not have any effect; (b) taurocholate had no inhibitory effect; (c) all of the organic anions studied, i.e., BSP, rose bengal, indocyanine green, and unconjugated bilirubin (UCB), manifested potent, dose-dependent inhibitory effects, with absence of toxic effects and complete reversibility of inhibition in the case of UCB. The inhibitory effects of UCB could be overcome partially by raising (CoCl2-induced) hepatic GSH concentration. Because of the physiological importance of UCB, we conducted a detailed study of its inhibitory kinetics in the isolated hepatocyte model in the range of circulating concentrations of UCB. Studies with Cl- -free media, to inhibit the uptake of UCB by hepatocytes, showed that the inhibition of GSH efflux by UCB is apparently from inside the cell. This point was confirmed by showing that the inhibition is overcome only when bilirubin-loaded cells are cleared of bilirubin (incubation with 5% bovine serum albumin). Using Gunn rat hepatocytes and purified bilirubin mono- and diglucuronides, we found that both UCB and glucuronide forms of bilirubin inhibit GSH efflux in a dose-dependent manner. We conclude that the organic anions, although taken up by a mechanism independent of GSH, may competitively inhibit the carrier for GSH efflux from inside the hepatocyte.