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We present and discuss the case of one patient that presented to the emergency room with abdominal pain in the right hypochondrium radiated to epigastrium and low-grade fever with blood test that shows dissociated colesthasis therefore admitted in the gastroenterology service with choledocholithiasis suspicion. cholangioresonance performed with a sudden stenosis of the bile duct in its intrapancreatic portion due a tumor in the pancreatic head. CT without lessions in other parts of the body. Upper endoscopy shows an ulcerated growth in the papillary area whose biopsies found neoplastic proliferation with S100, SOX10, MelanA and HMB45 positivity.

Lanthanum carbonate is a non-calcium phosphorus chelator used in the treatment of hyperphosphatemia associated with chronic renal disease. Deposits of lanthanum in the gastrointestinal wall have been recently described but its clinical significance is uncertain. We present a case of a 62-year-old male with chronic renal disease treated with lanthanum carbonate for 3 years, with deposits in his gastric mucosa, found on biopsy for dyspepsia. The deposits were acellular and of irregular shape, surrounded by macrophages and foreign body giant cells. The presence of lanthanum in the deposits was confirmed by X-ray spectroscopy. Diagnosis is reached with knowledge of its microscopic appearance and a thorough clinical history.

Purpose: To analyze the influence of adding gentamicin to a regimen consisting of β-lactam or vancomycin plus rifampicin on survival in patients suffering from Staphylococcal prosthetic valve endocarditis (SPVE). Methods: From January 2008 to September 2016, 334 patients with definite SPVE were attended in the participating hospitals. Ninety-four patients (28.1%) received treatment based on β-lactam or vancomycin plus rifampicin and were included in the study. Variables were analyzed which related to patient survival during admission, including having received treatment with gentamicin. Results: Seventy-seven (81.9%) were treated with cloxacillin (or vancomycin) plus rifampicin plus gentamicin, and 17 patients (18.1%) received the same regimen without gentamicin. The causative microorganism was Staphylococcus aureus in 40 cases (42.6%) and coagulase-negative staphylococci in 54 cases (57.4%). Overall, 40 patients (42.6%) died during hospital admission, 33 patients (42.9%) in the group receiving gentamicin and 7 patients in the group that did not (41.2%, P = 0.899). Worsening renal function was observed in 42 patients (54.5%) who received gentamicin and in 9 patients (52.9%) who did not (p = 0.904). Heart failure as a complication of endocarditis (OR: 4.58; CI 95%: 1.84–11.42) and not performing surgery when indicated (OR: 2.68; CI 95%: 1.03–6.94) increased mortality. Gentamicin administration remained unrelated to mortality (OR: 1.001; CI 95%: 0.29–3.38) in the multivariable analysis. Conclusions: The addition of gentamicin to a regimen containing vancomycin or cloxacillin plus rifampicin in SPVE was not associated to better outcome.

Primitive neuroectodermal tumors (PNET) are very rare tumors that belong to a family of malignant neoplasms of tiny round cells which are derived from the neural crest. This report discusses a rare case of an adult woman with esophageal PNET, confirmed by immunohistochemistry, that presented with metastasis to the pineal gland. To our knowledge, this is the first case report of a PNET with these features. Despite surgery and chemotherapeutic treatment, our case has shown disease progression.

Objective: To investigate the rate of colorectal neoplasms (CRNs) in patients who have Enterococcus faecalis infective endocarditis (EFIE) with available colonoscopies and to assess whether this is associated with the identification of a focus the infection. Patients and Methods: Retrospective analysis of data from a prospective multicenter study involving 35 centers who are members of the Grupo de Apoyo para el Manejo de la Endocarditis en Espana [Support Group for the Management of Infective Endocarditis in Spain] cohort. A specific set of queries regarding information on colonoscopy and histopathology of colorectal diseases was sent to each participating center. Four-hundred sixty-seven patients with EFIE were included from January 1, 2008, to December 31, 2017, from whom data on colonoscopy performance and results were available in 411 patients. Results: One hundred forty-two (34.5%) patients had a colonoscopy close to the EFIE episode. The overall rate of colorectal diseases was 70.4% (100 of 142), whereas the prevalence of CRN (advanced adenomas and colorectal carcinoma) was 14.8% (21 of 142), with no significant differences between the group of EFIE of unknown focus and that with an identified focus. Conclusion: Our study adds to prior evidence suggesting a much higher rate of CRN among patients with EFIE than in the general population of the same age and sex. In addition, our findings suggest that this phenomenon might take place both in EFIE with an unknown and an identified source of infection.

Background: There is little information concerning infective endocarditis (IE) in patients with bicuspid aortic valve (BAV) or mitral valve prolapse (MVP). Currently, IE antibiotic prophylaxis (IEAP) is not recommended for these conditions. Objectives: This study sought to describe the clinical and microbiological features of IE in patients with BAV and MVP and compare them with those of IE patients with and without IEAP indication, to determine the potential benefit of IEAP in these conditions. Methods: This analysis involved 3,208 consecutive IE patients prospectively included in the GAMES (Grupo de Apoyo al Manejo de la Endocarditis infecciosa en España) registry at 31 Spanish hospitals. Patients were classified as high-risk IE with IEAP indication (high-risk group; n = 1,226), low- and moderate-risk IE without IEAP indication (low/moderate-risk group; n = 1,839), and IE with BAV (n = 54) or MVP (n = 89). Results: BAV and MVP patients had a higher incidence of viridans group streptococci IE than did high-risk group and low/moderate-risk group patients (35.2% and 39.3% vs. 12.1% and 15.0%, respectively; all p < 0.01). A similar pattern was seen for IE from suspected odontologic origin (14.8% and 18.0% vs. 5.8% and 6.0%; all p < 0.01). BAV and MVP patients had more intracardiac complications than did low/moderate-risk group (50% and 47.2% vs. 30.6%, both p < 0.01) patients and were similar to high-risk group patients. Conclusions: IE in patients with BAV and MVP have higher rates of viridans group streptococci IE and IE from suspected odontologic origin than in other IE patients, with a clinical profile similar to that of high-risk IE patients. Our findings suggest that BAV and MVP should be classified as high-risk IE conditions and the case for IEAP should be reconsidered. Sin financiación 18.639 JCR (2018) Q1, 3/136 Cardiac & Cardiovascular Systems 9.280 SJR (2018) Q1, 1/365 Cardiology and Cardiovascular Medicine No data IDR 2018 UEM

A pesar de los grandes avances en la cardiologA­a en el siglo XX y XXI, la insuficiencia cardiaca sigue suponiendo la principal causa de hospitalizaciA³n en las personas ancianas y presentando un pronA³stico ominoso. AdemAis, a pesar de los mAoltiples estudios sobre nuevas dianas farmacolA³gicas, apenas hemos avanzado en el campo del tratamiento, tal vez porque aAon existen lagunas en su fisiopatologA­a. No debemos olvidar que la insuficiencia cardiaca es un compendio de signos y sA­ntomas que engloban mAoltiples A³rganos y sistemas.  Mucho se estAi investigando sobre la relaciA³n entre riA±A³n y corazA³n en forma de sA­ndrome cardiorrenal.  Algo cada vez mAis en boga es el papel del abdomen en la disfunciA³n orgAinica de la insuficiencia cardiaca. En ese sentido, el sistema venoso contiene el 70% del volumen sanguA­neo, siendo almacenado en su mayor parte dentro de las vA­sceras abdominales. Un aumento del tono simpAitico supone aumento intenso del retorno venoso tan importante como para  aumentar las presiones de llenado y justificar una descompensaciA³n cardiaca. La congestiA³n sistA©mica determina un aumento en la presiA³n intraabdominal que estAi correlacionada con la disfunciA³n renal en la insuficiencia cardiaca avanzada. La hipoperfusiA³n tisular intestinal supone microtraslocaciA³n bacteriana promoviendo el status proinflamatorio tA­pico de este sA­ndrome. La visiA³n holA­stica e integrada de la insuficiencia cardiaca puede suponer un avance tanto en la estratificaciA³n del riesgo como en las estrategias terapA©uticas. Grandes pasos se estAin dando en este sentido con estudios sobre la ultrafiltraciA³n, paracentesis, diAilisis peritoneal, suero hipertA³nico o fAirmacos adsorbentes del sodio.Â

All the currently available evidence suggests that the two types of inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC), involve a conflict between the immune system of the intestinal mucosa and intraluminal antigens, mainly the intestinal microflora, which are normally tolerated by the immune system. This conflict is modulated by numerous environmental factors and a clear polygenetic predisposition. The present article reviews the behavior of all the etiologic circumstances (microbial, genetic and environmental) and subsequently analyzes the possible pathogenic factors in which the etiologies can be found, namely: dysfunction of the intestinal epithelium, innate immune system alterations, and distortion of the cellular and humoral arms of the acquired immune system. The role of tissue ischemia in CD and expression of "extraintestinal inflammatory metastases", both in CD and UC, are briefly discussed. Finally, the view that IBD may be a spectrum of pathological processes provoked by distinct etiopathogenic factors and the possible biological significance of the growing incidence of this disease in the western world, coinciding with the decline in infectious diseases in this geographical area, are discussed.

There are several causes of damage and regeneration of the gastric epithelium (erosive gastropathy) and/or histological inflammation of the gastric mucosa (acute or chronic gastritis). After outlining the usual morphology of chronic gastritis, the authors attempt to identify the biological profile of the main pathogenic models. The first, and by far the most frequent, is the model associated with Helicobacter pylori, which, without crossing the mucosal epithelium, provokes an immune reaction. Although incapable of eradicating this bacterium, this immune reaction contributes to the inflammatory lesion provoked by H. pylori in the mucosa. The second -and much less frequent- model is that causing progressive atrophic gastritis through a humoral and cellular autoimmune mechanism. In third place are a group of models defined by a peculiar cytohistologic pattern of inflammation (granulomatous, lymphocytic or eosinophilic gastritis), suggesting similar pathogenic mechanisms for each of these rare morphological forms of gastritis. Lastly, there is a model barely fitting within the scope of this review, which is that provoking chemical gastropathies (bile reflux, NSAIDs, etc.) with minimal cellular inflammation, i.e., minimal gastritis. To aid understanding of the article, the authors provide a brief outline of the functional histology of the gastric wall and the mechanisms defending its integrity in physiological conditions.

In order to determine the relationship between the presence of pre-S1 and pre-S2 proteins and the level of hepatitis B virus (HBV) replication, a study of 94 HBsAg chronic carriers, 15 anti-HBe positive patients who suffered a viral reactivation and 12 HBeAg, HBV-DNA positive cases under antiviral therapy, has been carried out. Pre-S1 and pre-S2 antigens were detected by RIA using polystyrene beads coated with anti-preS1 or anti-preS2 (Dr W. Gerlich, Göttingen) and 125I-anti-HBs as tracer. The presence of pre-S1 and pre-S2 antigens was detected in 74 (79%) and 85 (90%), respectively, out of the 94 HBsAg chronic carriers included. The level of these antigens was significantly higher in HBeAg, HBV-DNA positive patients than in the other patients (p less than 0.05). Among anti-HBe positive patients suffering a reactivation, a significant increase of pre-S1 and pre-S2 levels was observed, concurring with ALT exacerbation and HBV-DNA positivity. After reactivation, the level of pre-S antigens returned to the basal values. A significant decrease in pre-S antigen levels (p less than 0.05) among patients who respond to recombinant interferon therapy was observed, while no changes were detected among non-responder cases. The detection of pre-S1 and pre-S2 antigens in serum is more frequent in those patients with high viral replication. Furthermore, among anti-HBe carriers with a viral reactivation, synthesis of pre-S antigens takes place again.

— The incidence of HBV-DNA polymerase, HBV-DNA and serum and liver HBcAg in 104 chronic HBsAg carriers was studied. HBV-DNA was the most frequently detected marker, followed by HBcAg and HBV-DNAp. According to their individual or combined presence, four different serological patterns of viral replication were discerned: 53 patients had all these markers, 30 had HBV-DNA but lacked HBV-DNAp (15 with and 15 without HBcAg) and 21 had no such markers detectable. The simultaneous positivity for all of those markers was observed only in HBeAg-positive patients. HBV-DNA alone or along with HBcAg was found in a similar incidence irrespective of the HBe system. Liver HBcAg was found in all but four patients with and in four without HBV-DNA. Viral DNA concentration was significantly (p < 0.001) higher when HBV-DNAp tested positive. Indeed, HBeAg rather than anti-HBe patients had higher (p < 0.005) levels of HBV-DNA. In HBeAg-positive patients, the nuclear HBcAg staining was significantly (p < 0.05) higher when HBV-DNAp tested positive. In DNA polymerase-negative patients, but positive for HBV-DNA, those with or without HBcAg had a similar percentage of core antigen staining. The same distribution was seen in anti-HBe, HBV-DNA-positive patients. However, the mean percentage of hepatocytes displaying cytoplasmic HBcAg did not differ significantly among patients with HBV-DNA, irrespective of the HBe system and the HBV-DNAp status. Such patients had significantly (p < 0.001) higher ALT levels than those without viral DNA. Active viral replication can be assessed differentially through any of these serum markers and is associated with liver cell necrosis.

— Twelve hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), hepatitis B virus DNA polymerase (HBV-DNAp) and hepatitis B virus DNA (HBV-DNA) positive patients with chronic active hepatitis (CAH) were treated with doses of either 20 times 106 IU/m2 or 10 times 106 IU/m2 body surface of recombinant interferon (rIFN)-alpha-2A, I.M., twice a week, during a period of 6 months. No appreciable differences with respect to clinical history, liver function tests and markers of HBV replication between the two groups were apparent at the time of entry into the trial. At the third month of treatment HBV-DNAp became negative in 10 out of 12 patients (83%). After a 15-month follow-up, HBV-DNAp, HBV-DNA and HBeAg were negative in 7 out of 12 patients (38%) (responders). Furthermore, at 24 months, 2 non-responder patients became HBV-DNA and HBV-DNAp negative and one responder lost serum HBsAg. In addition, HBsAg concentration, GPT level and histological Knodell's index decreased significantly in the responder patients, while no changes were observed in non-responders. Five out of six patients who received a low rIFN dose responded to the treatment, and only 2 out of 6 with a higher dose. No unacceptable toxicity was noted in any of the 12 patients. All of them completed the course of treatment. The results suggest that long-term rIFN-alpha-2A therapy has an antiviral effect in CAH due to HBV infection and is well tolerated.

Sera from 111 patients with chronic viral hepatitis and from 55 cases with other liver disorders were assayed for serum inhibitory factor. The prevalence of this immunosuppressive factor was very similar between chronic hepatitis B (61%), chronic hepatitis delta (57%) and chronic hepatitis C (68%). At the same time, serum inhibitory factor was never detected in the other disorders studied. The presence of this inhibitory factor was detected in a significantly higher percentage (p less than 0.05) of HBeAg, HBV-DNA positive cases (75%) than in anti-HBe positive, HBV-DNA negative cases (44.4%). In chronic hepatitis delta, this immunosuppressive factor was also related to HDV-RNA positivity. The detection of this serum immunosuppressive factor in chronic viral hepatitis and its association with a high viral replication level implies a possible role of this factor in the immune pathogenic mechanism in infectious viral hepatitis.

Mas del 90% de los tumores malignos del aparato digestivo pertenecen a la familia de los adenocarcinomas (ADC) y casi el 95% de estos presentan localizaciones gastricas (G), colorrectales (CR) o pancreaticas (P). Revisar las alteraciones geneticas que protagonizan los ADC de estas localizaciones y sus posibles coincidencias, junto a la correlacion histogenica de su gestacion, es el motivo de este trabajo. Las alteraciones geneticas que afectan a mas del 50% de los casos son: en los ADC-G, la inactivacion de los genes supresores de tumor p53, APC y DCC, en su variante «intestinal», la hipoexpresion de la caderina E en la variante «difusa» y la hiperexpresion de la ciclooxigenasa-2 y la ciclina D en la forma «intestinal»; en los ADC-CR, la inactivacion de los genes p53, APC y DCC, junto a la activacion mutacional del oncogen k-ras y, por ultimo, en los ADC-P, la inactivacion de los genes supresores p53, p16 y DPC4 junto a la activacion mutacional del oncogen k-ras. El ADC-P es el que muestra una marca genetica mas caracteristica y exclusiva, seguido del ADC-CR. Por ultimo, la correlacion histogenica en la secuencia tumorigena es mas evidente en los ADC-CR, seguidos de los ADC-P. La compleja realidad biologica de los ADC-G hace mas dificil dibujar tanto su perfil genetico como su correlacion histogenica. Para comprender mejor los argumentos de este trabajo, los autores recuerdan las bases geneticas y moleculares que regulan la vida y muerte de las celulas somaticas normales y el perfil biologico de las familias de genes principalmente involucrados en la carcinogenia.

Resumen Los tumores carcinoides gastrointestinales (TCa-GI) surgen desde celulas del sistema neuroendocrino difuso localizadas en el tracto digestivo y representan mas del 70% de todos los TCa de los seres humanos. En este trabajo se revisan los siguientes argumentos: 1) El perfil biologico de los TCa-GI (dibujo histopatologico, marcadores citoquimicos, alteraciones metabolicas, almacenamiento de neuroaminas y proteinas hormonales, comportamiento citodinamico y caracteristicas biologicas en funcion del origen embriologico). 2) Las circunstancias etiologicas (factores hereditarios excepcionales, asociacion de TCa gastricos con gastritis autoinmune, factores exogenos poco conocidos). 3) Aspectos patogenicos (mitogenesis persistente de celulas endocrinas asociada a hipergastrinemia, inactivacion de algunos presuntos genes supresores de tumor, dudosa participacion de oncogenes, accion autocrina de algunas proteinas estimuladoras de crecimiento celular).4) Las repercusiones de ciertos episodios fisiopatologicos (reaccion desmoplastica peritumoral responsable del «efecto masa» sobre el tubo digestivo, el «rapto» del triptofano alimentario por parte de las celulas tumorales hacia una via metabolica anormal, la facil diseminacion metastasica coexistente con una escasa agresividad tumoral, la liberacion al torrente sanguineo de productos secretores almacenados responsables del «sindrome carcinoide» y de algunos cuadros de hiperfuncion endocrina). Conviene recordar que los TCa-GI representan solo un segmento de los llamados tumores neuroendocrinos y, como tales, deben considerarse.

The possibility that carcinogenesis is a multiphasic process has been well demonstrated in colorectal cancer, at least in cancers arising from a benign adenomatous polyp. However, because of the difficulty of performing histopathological studies of the pancreas, the multiphasic nature of carcinogenesis is proving more difficult to demonstrate in pancreatic ductal adenocarcinoma (d-ADC), although a series of findings, reviewed in the present article, strongly support this characteristic. Firstly, d-ADC shows a fairly exclusive genetic-molecular profile, found in 70% of cases; this profile consists of the association of the K-ras oncogene and inactivation of the tumor suppressor genes p16, p53 and DPC4. Secondly, a series of lesions in the ductal epithelium, in healthy pancreatic tissue close to a d-ADC, have been identified, which seem to represent precancerous histopathological stages. Lastly, there is the suspicion that the mutations defining this genetic-molecular profile appear gradually, in a certain sequence, throughout the stages of progression. Most probably, rather than the order of appearance, the accumulation of these genetic-molecular events are what prompt quiescent ductal epithelium to progress to mitogenic cellular hyperplasia, leading to irreversible mutagenic cellular dysplasia.

Resumen El pancreas exocrino es una estructura funcionalmente peligrosa por estar expuesta a la autoagresion digestiva de sus enzimas mas agresivas (proteasas, etc.), a pesar de adoptar medidas de autoproteccion, como la sintesis de algunas de estas enzimas en forma de zimogenos inactivos (tripsinogeno, etc.). Se revisa la enfermedad inflamatoria del pancreas, realizando un analisis separado de sus formas clasicas de presentacion: las pancreatitis aguda (PA) y cronica (PC). Hay un consenso general de que el acontecimiento patogenico inicial de la PA es la activacion intraacinar del tripsinogeno a tripsina, seguida de la del resto de proenzimas, lo que origina un modelo insolito de inflamacion autofagica. Por el contrario, no hay acuerdo sobre el evento patogenico inicial de la PC (?lesion toxico-metabolica, estres oxidativo, hipertension ductal, etc.?), aunque en una parte de los casos parece evidente una secuencia patogenica de «necrosis-fibrosis» desde episodios reiterados de PA. Se comentan las areas etiopatogenicas compartidas por ambos procesos que justifican algunos intentos recientes de globalizacion patogenica. Todo ello invitaria a situar ambas formas clasicas de pancreatitis dentro del perimetro conceptual de una «enfermedad inflamatoria pancreatica por autoagresion enzimatica».

En el presente articulo se revisa la compleja realidad biologica del adenocarcinoma gastrico desde varios puntos de vista. Se trata de una neoplasia que se expresa histopatologicamente como un proceso dual (tipos intestinal y difuso) con una amplia diversidad citologica. Epidemiologicamente se comporta como una entidad con una profunda asimetria geografica y un perfil de incidencia cambiante, en declive. Presenta una etiologia multifactorial, en la que se combinan factores geneticos, infecciosos (Helicobacter pylori) , alimentarios y ambientales. Podria tener una gestacion multifasica desde lesiones precancerosas, aunque no siempre sigue una secuencia lineal. Solo conocemos parcelasfragmentarias de su patogenia, cuyo comun denominador es una activacion mitogena potencialmente mutagena de las celulas epiteliales implicadas. Conocer bien esta compleja realidad biologica nos permitira identificar mejores marcadores para un diagnostico precoz y puntos etiopatogenicos vulnerables para una prevencion y un tratamiento mas eficaces.

The major CRP (C-reactive protein) receptor on leucocytes has been identified as the low-affinity IgG receptor Fcgamma receptor II (CD32). Our aim was to assess whether inflammation may modify the presence of the CD32 receptor in BAEC (bovine aortic endothelial cells). Confocal microscopy experiments showed a weak expression of the CD32 receptor in control BAEC that was slightly increased by 10 microg/ml CRP. Incubation of BAEC with TNF-alpha (tumour necrosis factor-alpha) did not modify the fluorescence signal of CD32. Addition of CRP to TNF-alpha-incubated BAEC enhanced the fluorescence signal of the CD32 receptors. The CD32 receptors showed a perinuclear cytoplasmic localization in BAEC. An alteration of the NO (nitric oxide)-dependent vasorelaxation has been defined as endothelial dysfunction. Endothelial dysfunction has been associated with the presence of superoxide anion and with a reduction in the expression of the eNOS (endothelial NO synthase). A concentration of CRP similar to that detected in patients with cardiovascular risk (10 microg/ml) failed to modify the generation of superoxide anion stimulated by TNF-alpha. Western blot experiments showed that TNF-alpha decreased the expression of the eNOS protein, which was partially protected by treatment with 10 microg/ml CRP. The protective effect of 10 microg/ml CRP on eNOS expression in TNF-alpha-incubated BAEC was prevented by an antibody against CD32 receptors. In conclusion, the present results suggest that, although CRP has been associated with inflammation, CRP may protect the expression of eNOS protein against pro-inflammatory mediators such as TNF-alpha.

Introduccion y objetivos Valorar la capacidad diagnostica de un protocolo de estudio del sincope de causa indeterminada que utiliza, selectivamente, los estudios electrofisiologicos y las pruebas de tabla basculante. Pacientes y metodo El estudio se realizo en 137 pacientes consecutivos (94 varones y 43 mujeres, con una edad media de 57,6 ± 18,3 anos), con sincope de causa indeterminada tras la evaluacion clinica inicial, que fueron divididos en dos grupos. El grupo A estaba compuesto por 77 pacientes que cumplian alguno de los siguientes criterios: a) presencia de cardiopatia estructural; b) ECG anormal; c) presencia de arritmias significativas no sintomaticas en el Holter, y d) presencia de palpitaciones paroxisticas. Estos pacientes fueron sometidos inicialmente a estudio electrofisiologico. El grupo B estaba compuesto por 60 pacientes que no cumplian ninguno de los criterios anteriores y fueron sometidos en un principio a pruebas de tabla basculante. Resultados En el grupo A el estudio electrofisiologico fue positivo en 43 pacientes (55%). En el grupo B el test de basculacion fue positivo en 41 pacientes (68%). De los pacientes del grupo A con estudio negativo, 20 (59%) fueron sometidos a test de tabla basculante, con 7 positividades (35%). Cinco pacientes del grupo B con test de basculacion negativo fueron sometidos a estudio electrofisiologico, que fue negativo en todos ellos. Globalmente se consiguio un diagnostico positivo en 91 de 137 pacientes (66%). Conclusiones En pacientes con sincope de causa inaparente en la evaluacion inicial, la utilizacion dirigida de manera selectiva por criterios clinicos, bien de estudios electrofisiologicos bien de pruebas de tabla basculante, permite establecer un diagnostico positivo en mas del 60% de los casos. Nuestros resultados sugieren que el test de tabla basculante deberia ser realizado en aquellos casos del grupo A con estudio electrofisiologico negativo.

To assess possible role of testing for IgM-specific antibody in the diagnosis and monitoring of patients with hepatitis C, we tested sera from 14 patients with acute and 97 patients with chronic non-A, non-B hepatitis for IgG and IgM antibody to hepatitis C virus. IgG antibody to hepatitis C virus was detected in 93% of acute cases and 91% of chronic cases. Of the 101 patients with IgG antibody to hepatitis C virus, 57% had IgM antibody to hepatitis C virus. None of the 20 healthy subjects or 40 patients with acute or chronic hepatitis A or hepatitis B had IgM antibody to hepatitis C virus. At the onset of clinical symptoms in acute hepatitis C, IgG antibody to hepatitis C virus was detected in 8 (57%) and IgM antibody to hepatitis C virus in 9 of 14 patients (64%). Eventually, both IgG and IgM antibody to hepatitis C virus became detectable in 13 of 14 patients with acute hepatitis C. Seven patients with antibody to hepatitis C virus resolved the acute infection within 6 mo and all seven cleared IgM antibody to hepatitis C virus, whereas two cleared IgG antibody to hepatitis C virus. Six patients had a chronic outcome of the acute infection and IgM antibody to hepatitis C virus persisted in detectable amounts for more than 6 mo in all (mean = 15.5 mo). Among 88 patients with chronic non-A, non-B hepatitis with IgG antibody to hepatitis C virus, IgM antibody to hepatitis C virus was detected in 45 (51%).(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic hepatitis C is often a progressive liver disease for which there is no satisfactory treatment. We studied the efficacy of recombinant alpha-interferon or gamma-interferon in the treatment of this disease in comparison with a control group. Thirty patients were randomly assigned to three groups. Ten patients received 7.5 MU alpha-interferon/m2 body surface three times weekly for 3 mo, then 5 MU/m2 for 3 mo and 2.5 MU/m2 for 6 mo. Ten patients were treated with gamma-interferon at a dose of 2 MU/m2 for 6 mo and the other 10 served as controls without treatment. The mean serum ALT levels and liver histological findings improved significantly only in the patients treated with alpha-interferon. No changes were observed in patients treated with gamma-interferon or in controls. Five of 10 patients treated with alpha-interferon had complete responses (mean ALT normal during therapy). After treatment ALT returned to pretreatment levels in two of 5 patients. The long-term response rate after alpha-interferon therapy was 30% at 18 mo. We conclude that alpha-interferon is effective in controlling disease activity in a portion of patients with chronic hepatitis C. High doses of alpha-interferon do not appear to add further benefit in the response rate or relapse rate. gamma-Interferon therapy is ineffective.

Chronic hepatitis C is often a progressive liver disease for which there is no satisfactory treatment. We studied the efficacy of recombinant alpha-interferon or gamma-interferon in the treatment of this disease in comparison with a control group. Thirty patients were randomly assigned to three groups. Ten patients received 7.5 MU alpha-interferon/m2 body surface three times weekly for 3 mo, then 5 MU/m2 for 3 mo and 2.5 MU/m2 for 6 mo. Ten patients were treated with gamma-interferon at a dose of 2 MU/m2 for 6 mo and the other 10 served as controls without treatment. The mean serum ALT levels and liver histological findings improved significantly only in the patients treated with alpha-interferon. No changes were observed in patients treated with gamma-interferon or in controls. Five of 10 patients treated with alpha-interferon had complete responses (mean ALT normal during therapy). After treatment ALT returned to pretreatment levels in two of 5 patients. The long-term response rate after alpha-interferon therapy was 30% at 18 mo. We conclude that alpha-interferon is effective in controlling disease activity in a portion of patients with chronic hepatitis C. High doses of alpha-interferon do not appear to add further benefit in the response rate or relapse rate. gamma-Interferon therapy is ineffective.

We have analyzed the presence of IgG and IgM anti-calmodulin antibodies (anti-CaM) by ELISA in patients with chronic hepatitis due to B, delta and C viruses as well as in patients with other liver diseases. The specificity of the assay was demonstrated by preadsorption of positive serum with calmodulin (CaM) but not with myosin light chain. Among 164 patients with chronic viral hepatitis (B, delta and C) and 50 with non-viral hepatitis, 27 and 26%, respectively, had auto antibodies against CaM. There was a significantly increased frequency (37%) of these auto-antibodies in chronic delta infection as compared to that (21%) of patients with chronic B hepatitis (p less than 0.05). An intermediate incidence of anti-CaM, (24%) was found in chronic C infection. The frequency of anti-CaM was not related to the level of hepatitis B virus (HBV) or hepatitis delta virus (HDV) replication. A high occurrence of anti-CaM in the presence of liver membrane antibody (p less than 0.03) was observed. During follow-up of patients with chronic delta-hepatitis, the presence of anti-CaM was consistently observed, when the isotype was IgM, but transiently when it was IgG. The occurrence of anti-CaM correlated neither with ALT levels nor with histological diagnosis. Antibodies to CaM, are present in liver diseases especially in chronic delta-hepatitis, and do not play a pathogenic role on hepatocellular damage.

All the currently available evidence suggests that the two types of inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC), involve a conflict between the immune system of the intestinal mucosa and intraluminal antigens, mainly the intestinal microflora, which are normally tolerated by the immune system. This conflict is modulated by numerous environmental factors and a clear polygenetic predisposition. The present article reviews the behavior of all the etiologic circumstances (microbial, genetic and environmental) and subsequently analyzes the possible pathogenic factors in which the etiologies can be found, namely: dysfunction of the intestinal epithelium, innate immune system alterations, and distortion of the cellular and humoral arms of the acquired immune system. The role of tissue ischemia in CD and expression of "extraintestinal inflammatory metastases", both in CD and UC, are briefly discussed. Finally, the view that IBD may be a spectrum of pathological processes provoked by distinct etiopathogenic factors and the possible biological significance of the growing incidence of this disease in the western world, coinciding with the decline in infectious diseases in this geographical area, are discussed.

Over 90% of digestive tract malignancies are adenocarcinomas (ADC) and almost 95% of them have gastric (G), colorectal (CR) or pancreatic (P) localizations. The objectives of this work are to review the genetic abnormalities of ADC in these locations and their potential coincidences, along with the histogenetic correlation of their emergence. Genetic abnormalities affecting over 50% of cases include: in G-ADC, inactivation of suppressor genes of p53, APC and DCC tumor in its intestinal variant, hypoexpression of of caderine E in the diffuse variant and hyperexpression of cyclooxygenase-2 and cyclyn D in the intestinal form; in in CR-ADC, inactivation of of genes p53, APC and DCC together with mutational activation of k-ras oncogen, and in P-ADC, the inactivation of suppressor genes p53, p16 and DPC4 along with mutational activation of k-ras oncogen. P-ADC is the one showing a more characteristic and exclusive genetic mark, followed by CR-ADC. Finally, the histogenetic correlation in the tumorigenic sequence is more evident in CR-ADC, followed by P-ADC. The complex biologic reality of G-ADC makes it more difficult to draw its genetic profile and its histogenetic correlation. In order to understand better the arguments of this work, the authors comment on the genetic-molecular basis governing the life and death of normal somatic cells and the biologic profile of the groups of genes mainly involved in tumorigenesis.

Gastrointestinal carcinoid tumors arise from cells of the diffuse neuroendocrine system localized in the digestive trace and represent more than 70% of all carcinoid tumors in humans. The present article reviews the following topics: 1) The biological profile of these tumors (histopathology, cytokine markers, metabolic alterations, storage of neuroamines and hormonal proteins, cytodynamic behavior, and biological behavior according to embryological origin). 2) The etiological circumstances (exceptional hereditary factors, association of gastric carcinoid tumors with autoimmune gastritis, little-known exogenous factors). 3) Pathogenic aspects (persistent mitogenesis of endocrine cells associated with hypergastrinemia, inactivation of some putative tumor suppressor genes, the doubtful participation of oncogenes, autocrine action of some cellular growth-stimulating proteins). 4) The repercussions of certain physiopathological events (peritumoral desmoplastic reaction causing the "mass effect" on the digestive tube, the "kidnapping" of dietary tryptophan by tumoral cells toward an abnormal metabolic pathway; the easy metastatic dissemination coexisting with low tumoral aggressivity, and the release into the bloodstream of stored secretory products leading to "carcinoid syndrome" and some endocrine hyperfunction syndromes. Finally, it should be remembered that gastrointestinal carcinoid tumors represent only a proportion of the neoplasms classified as neuroendocrine tumors.

There are several causes of damage and regeneration of the gastric epithelium (erosive gastropathy) and/or histological inflammation of the gastric mucosa (acute or chronic gastritis). After outlining the usual morphology of chronic gastritis, the authors attempt to identify the biological profile of the main pathogenic models. The first, and by far the most frequent, is the model associated with Helicobacter pylori, which, without crossing the mucosal epithelium, provokes an immune reaction. Although incapable of eradicating this bacterium, this immune reaction contributes to the inflammatory lesion provoked by H. pylori in the mucosa. The second -and much less frequent- model is that causing progressive atrophic gastritis through a humoral and cellular autoimmune mechanism. In third place are a group of models defined by a peculiar cytohistologic pattern of inflammation (granulomatous, lymphocytic or eosinophilic gastritis), suggesting similar pathogenic mechanisms for each of these rare morphological forms of gastritis. Lastly, there is a model barely fitting within the scope of this review, which is that provoking chemical gastropathies (bile reflux, NSAIDs, etc.) with minimal cellular inflammation, i.e., minimal gastritis. To aid understanding of the article, the authors provide a brief outline of the functional histology of the gastric wall and the mechanisms defending its integrity in physiological conditions.

The presence of hepatitis B virus DNA was studied in peripheral blood mononuclear cell samples from 259 HBsAg carriers (229 anti-hepatitis delta negative, 30 anti-hepatitis delta positive), 16 anti-HBc—positive HBsAg-negative patients and 30 patients without hepatitis B virus markers. Hepatitis B virus DNA sequences were detected in peripheral blood mononuclear cell from 115 (44.4%) of the chronic HBsAg carriers and from two (12%) of the anti-HBc—positive, HBsAg-negative patients. In anti-hepatitis delta—negative patients, viral DNA was positive in peripheral blood mononuclear cell from 74 (46%) and from 24 (35.5%) with and without serum HBV-DNA, respectively. With respect to anti-hepatitis delta—positive patients, viral DNA was found in peripheral blood mononuclear cell in 8 of 13 (61.5%) of the patients with circulating hepatitis delta virus RNA and in 9 of 17 (53%) of the hepatitis delta virus RNA—negative subjects. Regarding hepatitis B virus DNA in serum and peripheral blood mononuclear cell, 71% (5 of 7) of the patients with serum hepatitis B virus DNA had this marker in peripheral blood mononuclear cell, whereas 52% (12 of 23) of the patients without serum hepatitis B virus DNA had hepatitis B virus DNA in peripheral blood mononuclear cell. A Southern blot analysis was also carried out on peripheral blood mononuclear cell samples from 30 patients. Hepatitis B virus DNA was detected in 16 patients as free forms, in 12 patients as dimers and free forms and as free circular together with free linear forms in the remaining two patients. In conclusion, there is no relation between the viral replication level and the presence of hepatitis B virus DNA in peripheral blood mononuclear cell. Hepatitis delta virus does not seem to affect the presence of hepatitis B virus DNA in peripheral blood mononuclear cell. (HEPATOLOGY 1990;12:1290–1294).

To determine the possible changes in the presence and level of anti-idiotype (anti-Id) antibodies against anti-HBs induced by recombinant interferon (rIFN) therapy in chronic hepatitis B virus (HBV) infection, a study of patients under rIFN treatment has been carried out. A total of 62 (38 treated and 24 controls), HBeAg and HBV-DNA positive HBsAg carriers were tested serially for the presence of IgG and IgM anti-Id antibodies. According to serological evolution, treated patients were divided in responders (HBeAg and HBV-DNA became negative) (n = 18) and nonresponders (n = 20). Control patients were also classified as having spontaneous seroconversion (n = 11) and without changes (n = 13). Basally all patients had IgG and IgM anti-Id. At the end of the follow-up period (15th month), a significant decrease was observed in the percentage of cases positive to anti-Id among rIFN-responders (IgG, 67%, p less than 0.01; IgM, 44%, p less than 0.001). In contrast, only one nonresponder lost IgM anti-Id during the study. Among controls, only one with spontaneous loss of HBV-DNA and HBeAg clearance became negative to both IgG and IgM anti-Id. In addition, in the basal sample, the rIFN-responders had significantly lower anti-Id levels than the nonresponders (p less than 0.05). Similar results were obtained when comparing the controls with or without spontaneous response (p less than 0.05). Furthermore, a significant decrease in the anti-Id levels among the rIFN responders at the 9th month was detected (p less than 0.01). In summary, the anti-Id antibodies decreased significantly in patients who became HBV-DNA negative following rIFN administration. This result confirms the close relationship between HBV replication and the anti-idiotype against anti-HBs.

The patterns of hepatitis B virus DNA (HBV-DNA) expression were studied in 2 sequential liver biopsies from 26 children (18 treated with interferon and 8 controls) with chronic hepatitis B. In the basal biopsy replicative forms of HBV-DNA were detected in all of the samples and integrated viral DNA was present in 1 case. At the end of the study, 8 children had lost serum HBV-DNA although 2 of the children were still HBeAg positive. (Six had been treated with interferon.) In all of the cases, HBV-DNA was not detectable in the final biopsy. For the rest of the patients, HBV-DNA was positive in serum and all of them had replicative forms of HBV-DNA in the second liver sample. None of the patients lost hepatitis B surface antigen (HBsAg). Peripheral blood mononuclear cells (PBMC) from these patients were studied. HBV-DNA was not found in the PBMC of the 8 children without serum HBV-DNA, and HBV-DNA was detected in the PBMC of 5/12 patients with serum HBV-DNA. In conclusion, HBV-DNA disappeared from the biopsies of children who lost circulating HBV-DNA, although some of the patients were still HBeAg positive. This result implies that the detection of HBV-DNA in liver is important in order to assess the efficacy of the antiviral therapy. On the other hand, HBsAg remained positive in all children at the end of the study although HBV-DNA was not detected in serum, liver, and PBMC by the conventional hybridization techniques.

The possibility that carcinogenesis is a multiphasic process has been well demonstrated in colorectal cancer, at least in cancers arising from a benign adenomatous polyp. However, because of the difficulty of performing histopathological studies of the pancreas, the multiphasic nature of carcinogenesis is proving more difficult to demonstrate in pancreatic ductal adenocarcinoma (d-ADC), although a series of findings, reviewed in the present article, strongly support this characteristic. Firstly, d-ADC shows a fairly exclusive genetic-molecular profile, found in 70% of cases; this profile consists of the association of the K-ras oncogene and inactivation of the tumor suppressor genes p16, p53 and DPC4. Secondly, a series of lesions in the ductal epithelium, in healthy pancreatic tissue close to a d-ADC, have been identified, which seem to represent precancerous histopathological stages. Lastly, there is the suspicion that the mutations defining this genetic-molecular profile appear gradually, in a certain sequence, throughout the stages of progression. Most probably, rather than the order of appearance, the accumulation of these genetic-molecular events are what prompt quiescent ductal epithelium to progress to mitogenic cellular hyperplasia, leading to irreversible mutagenic cellular dysplasia.

The exocrine pancreas is a functionally dangerous structure since it is exposed to digestion by its most aggressive enzymes (proteases, etc) despite self-protective measures such as the synthesis of some of these enzymes in the form of inactive zymogens (trypsinogen, etc.). We review inflammatory pancreatic disease by separately analyzing its classical forms of onset: acute and chronic pancreatitis (AP and CP). There is general consensus that the initial pathogenic event in AP is intraacinar activation of trypsinogen into trypsin, followed by that of the remaining proenzymes, giving rise to an unusual model of autophagic inflammation. In contrast, consensus is lacking on the initial pathogenic event in CP (toxic-metabolic lesion, oxidative stress, ductal hypertension, etc.?), although in some cases anecrosis-fibrosissequence due to recurrent episodes of AP seems evident. The pathogenic features shared by both forms of the disease and which justify some recent attempts to formulate an overall explanation of the pathogenesis of pancreatitis are discussed. Such an explanation would place both forms of pancreatitis within the conceptual framework of aninflammatory pancreatic disease due to enzyme autodigestion.