Propiedades morfológicas en la parte media de la díafisis del hueso metacarpiano III de equino mestizo criollo / Morphological properties in the mid part of the metacarpal III bone diaphysis of equine criollo crossbreed

El desarrollo del esqueleto es de máxima importancia en caballos de trabajo y alta competencia. Los miembros torácicos sostienen el 60% del peso corporal y están sometidos a esfuerzos biomecánicos que los predisponen a lesiones, estando obligados a especializarse en el apoyo. El metacarpiano III soporta la mayor carga entre los huesos del cuerpo y la sustancia compacta tiene gran espesor dorsal y medial. Es un material complejo que posee plasticidad y fuerza considerable, con capacidad para soportar la deformación y recuperar su forma. El objetivo de este estudio es aportar conocimientos morfológicos, aplicables a la clínica animal, del hueso metacarpiano III de equino mestizo criollo. Se estudiaron los huesos metacarpiano III de 30 equinos hembras y machos, entre 18 meses y 5 años de edad, divididos en dos grupos etarios, provenientes del frigorífico General Pico, Las Higueras. Se determinó: peso y longitud total; diámetro latero-medial y dorso-palmar en la parte media de la diáfisis. Al metacarpiano III izquierdo se le practicó una osteotomía transversal en la parte media de la diáfisis para determinar: espesor de la cortical, área cortical, área medular y área total. Los datos fueron analizados mediante técnicas de correlación y regresión lineal simple, análisis de la varianza y comparaciones múltiples de Tukey usando el paquete estadístico InfoStat, con un nivel de significación de 0,05. Los resultados muestran que existe asociación entre el peso versus área cortical (r= 0,76, p= 0,0001) y longitud del hueso versus área cortical (r= 0,74 p= 0,0001), el área depende linealmente del peso y longitud del hueso (R2= 0,97, p<0,0001 y R2= 0,96, p<0,0001 respectivamente). Se comprobó que existen diferencias significativas entre los diámetros de las áreas y espesor de los cuadrantes (p<0,0001), al contrastar los cuadrantes entre sí se observaron diferencias a excepción del cuadrante dorsal y lateral. Existe diferencias entre las áreas de los distintos grupos etários (p= 0,0034). La morfología tiene influencia sobre las propiedades biomecánicas del hueso.

The development of high skeleton is important in working horses and associated high competition. Thoracic members hold 60% of body weight and are subjected to biomechanical efforts that predispose the animal to injury, being forced to rely on the support. The large metacarpal III supports load between bones of the body and the compact substance is large dorsal and medial thickness. It is composed of complex material and possesses plasticity and considerable force, with the ability to sustain deformation and subsequently recover its form. The objective of this study is to provide morphometric knowledge applied to animal clinic of the metacarpal III bone of equine criollo crossbreed. Thirty (30) metacarpal III bones of male and female horses, between 18 months and 5 years old, divided into two age groups, from the Frigorifico General Pico, Las Higueras groups were studied. We determined: weight, total length, diameter latero-medial and dorsal-palmar in the middle of the diaphysis. A transverse osteotomy was performed left to metacarpal III in the middle diaphysis to determine: cortical thickness, cortical area, medullary area and total area. The data was analyzed by correlation and simple linear regression techniques, analysis of variance and Tukey multiple comparisons using the statistical InfoStat (2009) package, with a significance level of 0.05. The results showed an association between weight vs. cortical area (r= 0.76, p= 0.0001) and bone length vs. cortical area (r= 0.74, p= 0.0001), the area depends linearly on the weight and length bone (R2= 0.97, p<0.0001 and R2= 0.96, p<0.0001 respectively). It was found that there are significant differences between the diameters of the area and thickness of the quadrants (p<0.0001), contrasting quadrants were observed in the dorsal and lateral exception quadrant. There are differences between areas of different age groups (p= 0.0034). The morphology influences the biomechanical properties of the bone.

Características mecánicas dinámicas de la tibia aislada de perro sometida a prueba de impacto / Dynamic mechanical characteristics of the isolated dog tibia, subjected to impact test

El propósito del presente trabajo es brindar información acerca de las propiedades biomecánicas y morfológicas de la tibia de perro sometida a cargas dinámicas. Los objetivos fueron evaluar la resistencia de la tibia frente al impacto mediante el Método de Ensayo Charpy, relacionar la misma con el área total, el área cortical y el área de la cavidad medular del hueso, comparándola entre talla, edad y sexo diferente. La importancia clínica, ortopédica y quirúrgica que reviste la región de la pierna del perro fundamenta esta investigación. Se utilizaron tibias de perro en condiciones aisladas, extraídas postmortem de 30 animales mestizos adultos jóvenes provenientes del servicio de zoonosis de la ciudad de Río Cuarto. Se determinó en la tibia derecha e izquierda: peso y longitud total del hueso, diámetros cráneo-caudal y latero-medial en la mitad de la diáfisis. A la tibia izquierda se le practicó osteotomía transversal en la mitad de su diáfisis. En la superficie de sección se midió: espesor de la cortical, diámetro medular y se obtuvo el área de sección total, área cortical y área medular. La tibia derecha fue sometida al Método de Ensayo Charpy. Se realizó el análisis estadístico correspondiente. La resistencia del hueso presentó una correlación de r=0,70 (p= 0,000019); r=0,67 (p=0,000059) y r=0,29 (p=0,12) con respecto a las áreas cortical, total y medular respectivamente. La morfología tiene influencia sobre las propiedades biomecánicas del hueso. A medida que aumenta el área cortical aumenta la energía de impacto absorbida. En cambio, a mayor área de cavidad medular la energía de impacto absorbida aumenta pero en menor magnitud. Existen diferencias estadísticamente significativas (p=0,0168) entre la talla del animal y la resistencia de la tibia. La edad (p=0,73) y el sexo (p=0,18) no presentaron influencias significativas sobre las propiedades biomecánicas de la tibia.

The purpose of this work is to provide information about biomechanical and morphological properties of the dog tibia bone subject to dynamic loads. The objectives were: evaluate the resistance of the tibia subject impact used Charpy test Method; linking it with total area, cortical area and bone marrow cavity; and compare it with weight, age and sex categories. The clinical, orthopedical and surgical relevance of the dog leg region is the basis for this research. Dog tibia were used in isolated conditions, removed postmortem from 30 adult animals defined raceless, from the zoonoses service of the city of Río Cuarto. Weight and total bone length, cranial-caudal and lateral-medial diameter in the middle of the diaphysis, were determined in the left and right tibia. The left tibia was osteotomized transversely in the middle of the diaphysis. On the surface section we measured: cortical thickness, diameter of the bone marrow cavity, and obtained the total section area, cortical area and medullary area. The right tibia was subjected to Charpy test method. Statistical analysis was performed accordingly. The bone strength showed a correlation of r=0.70 (p= 0.000019); r=0.67 (p=0.000059) and r=0.29 (p=0.12) with respect to the cortical area, total area and medullary area respectively. The morphology has influence on the biomechanical properties of bone, with increasing cortical area increases the impact energy absorbed. In contrast, a greater area of the medullary cavity of impact energy absorbed increases but to a lesser magnitude. There were statistically significant differences (p=0.0168) of size on the strength of the tibia. Age (p=0.7343) and sex (p=0.1898) had no significant influence on the biomechanical properties of the tibia.

Características mecánicas dinámicas del fémur aislado de perro, sometido a prueba de impacto / Dynamic mechanical characteristics of the isolated dog femur, subjected to impact test

El presente trabajo tiene el propósito de brindar información acerca del comportamiento biomecánico del fémur de perro sometido a cargas dinámicas. El objetivo es evaluar la resistencia del fémur frente al impacto, mediante el Método de Ensayo Charpy, relacionando dicha resistencia con las áreas: total, cortical y cavidad medular del hueso, comparándola entre edad y sexo diferentes. Se utilizaron fémur de perro en condiciones aisladas, extraídos postmortem de 30 animales mestizos adultos, provenientes del servicio de zoonosis de la ciudad de Río Cuarto. Se determinó en los fémures derecho e izquierdo: peso y longitud total del hueso, diámetro cráneo-caudal y latero-medial en la mitad de la diáfisis. El fémur izquierdo fue osteotomizado transversalmente en la mitad de su diáfisis. En la superficie de sección se medió espesor de la cortical y diámetro medular. Se obtuvo el área de sección total, cortical y medular. El fémur del miembro pélvico derecho fue sometido al Método de Ensayo Charpy. Los resultados obtenidos fueron analizados estadísticamente encontrándose que el área cortical depende linealmente de la longitud del hueso (r=0,62, p= 0,00025); la resistencia del hueso depende de las áreas cortical (r=0,71, p= 0,000012) y área total (global) (r=0,63, p= 0,00021) y no del área medular (r=0,29, p= 0,12). El análisis exploratorio muestra que no existirían diferencias acerca de la influencia de la edad y el sexo sobre la resistencia del fémur. Tras estos resultados se puede inferir que a medida que aumenta el área cortical aumenta la energía de impacto absorbida.

This paper is intended to provide information about biomechanical behavior femur at impact using the Charpy test method relating the resistance in the following areas: total, cortical and medullary bone cavity, comparing these between different ages and sexes. Dog femors were used in isolated conditions, removed postmortem from 30 adult animals, defined raceless, from the zoonoses service of the city of Rio Cuarto. Weight, total bone length, cranio-caudal diameter and lateral medial half of the diaphysis, were determined in the left and right femur. The left femur was osteotomized transversely in the middle of the diaphysis. In the sectional area thickness of the cortical and medullary diameters were measured. We obtained the total sectional area, cortical and medullary. The femur of the right lower limb was subjected to the Charpy test method. Results were statistically analyzed and found that cortical area depends linearly on the length of the bone (r=0.62, p=0.00025), bone strength depends on the cortical areas (r=0.71, p=0.00012) and total (global) areas (r=0.63, p=0.00021) and not of the medullary area (r=0.29, p=0.12). Exploratory analysis showed that no difference existed regarding age and sex influence on the strength of the femur. Following these results we can infer that as cortical area increases, the impact energy absorbed also increases.

Quantification of copper phases, their reducibility and dispersion in doped-CuCl2/Al2O3 catalysts for ethylene oxychlorination.

The comprehensive understanding of the composition, behaviour and reactivity of a catalyst used inside industrial plants is an extremely hard task that is rarely achieved. It requires the use of different spectroscopic techniques, applied under in situ or in operando conditions, and combined with the investigation of the catalyst activity. Often the operating experimental conditions are different from technique to technique and the different results must be compared with care. In the present contribution, we combined in situ XANES/EXAFS, IR spectroscopy of adsorbed CO, CO chemisorption and catalytic tests performed using a pulse reactor in depletive mode. This multitechnical approach resulted in the understanding of the role that dopants (LiCl, KCl, CsCl, MgCl(2) LaCl(3)) have in the nature, relative fraction, reducibility and dispersion of Cu-phases on CuCl(2)/gamma-Al(2)O(3) catalysts for oxychlorination reaction, a key step of the PVC chemistry. In the undoped catalyst two Cu phases coexist: Cu-aluminate and supported CuCl(2), being the latter the only active one [J. Catal., 2000, 189, 91]. EXAFS and XANES highlighted that all dopants contribute more or less efficiently in increasing the fraction of the active copper species, that reaches a value of almost 100% in the case of MgCl(2) or LaCl(3). EXAFS directly, and IR indirectly, proved that the addition of KCl or CsCl (and less efficiently of LiCl) results in the formation of mixed CuK(x)Cl(2+x) or CuCs(x)Cl(2+x) phases, so altering the chemical nature of the active phase. XANES spectroscopy indicates that addition of MgCl(2) or LaCl(3) does not affect the reducibility by ethylene (under static conditions) of the active CuCl(2) phase and that the reducibilility of the new copper-dopant mixed chloride are in the order CuCl(2) > CuLi(x)Cl(2+x) > CuK(x)Cl(2+x) > CuCs(x)Cl(2+x). However, when reduction is done inside a pulse reactor, a more informative picture comes out. The last technique is able to differentiate all samples, and their ability to be reduced by ethylene resulted in the order: La- > Mg- > Li-doped > undoped > K- > Cs-doped catalyst. To understand this apparent discrepancy the dispersion of the active phase, measured by CO chemisorption, was needed: it has been found that addition of LiCl increases enormously the dispersion of the active phase, LaCl(3) significantly and MgCl(2) barely, while addition of both KCl and CsCl results in a decrease of the surface area of the active phase. The mechanism of the enhancing effect of La and Mg on catalytic activity is still not clear, but it could be associated to the modification that they induce to the support surface: the Cu is so highly dispersed that almost all is in direct contact with support surface. It is finally worth noticing that the previous EXAFS and XANES study allowed us to refer the chemisorption data to the active phase only, while the IR study allowed us to fix the Cu(+)/CO surface stoichiometry. Summarizing the use of a multidisciplinary approach has been the conditio sine qua non (mandatory condition) to understand the complex role that the different additives have on the active phase of the CuCl(2)/gamma-Al(2)O(3) catalysts for ethylene oxychlorination.

Análisis multivariado aplicado a la etapa de deshidratación en la técnica de plastinación del riñón de caballo / Multivaried analysis applied at the stage of dehydration in the plastination technique in horse´s kidney

La Plastinación es la técnica más moderna para la conservación de piezas anatómicas y especímenes. Esta técnica consta de cuatro etapas: fijación, deshidratación, impregnación forzada y curado. Este trabajo pretende mejorar la eficiencia en la producción de órganos plastinados mediante la técnica de Plastinación estándar denominada S 10. Se utilizaron riñones de equinos mestizos criollos provenientes del Frigorífico Aimar S/A, ubicado en la zona rural de Río Cuarto. Luego de realizar la fijación del órgano con formalina se procedió a deshidratarlo. La deshidratación se llevó a cabo en tres sub-etapas donde en cada una de ellas se trabajó a la misma temperatura y se utilizó como solvente una solución de acetona en diferentes concentraciones. Las mediciones se realizaron con acetómetro registrándose el tiempo insumido para lograr la deshidratación. Los datos se analizaron estadísticamente por medio de: análisis de la varianza multivariada y análisis de correlación simple utilizando el paquete estadístico InfoStat. Los resultados muestran que los tiempos de deshidratación se ven influenciados por la edad del animal pero no por la posición ni por el peso del órgano.

Plastination is the most modern technique for the preservation of anatomical pieces and specimens. This technique consists of four stages: fixation, dehydration, forced impregnation, and cured. This research aims at improving the efficiency of production plastinated organs through the standard technique known as S10. Kidneys of criole mestizo equines from Frigorifico Aimar S.A placed in the rural area of Rio IV were used. After binding the organ with formalin, it was dehydrated. The dehydration was carried out in three sub-stages working at the same temperature, and a solvent composed of solution of acetone of different concentrations was used. The measurements were analysed with acetometer, keeping register of the time consumption to reach dehydration. The resulting data was statistically analysed using Infostat program. Results showed that the time consumed to reach dehydration was influenced by the horses age but not by the kidney's weight, there were no significant differences between right and left kidneys neither.

Transient elastography: a new surrogate marker of liver fibrosis influenced by major changes of transaminases.

Liver stiffness was measured by transient elastography (FibroScan) in 228 consecutive patients with chronic viral hepatitis, with (115) or without cirrhosis (113), to study its correlations with serum transaminases [alanine aminotransferase (ALT)], fibrosis stage and surrogate noninvasive markers of fibrosis (APRI, FORNS, FibroTest and hyaluronic acid). The dynamic profiles of serum transaminases and liver stiffness were compared by multiple testing in 31 patients during a 6-month follow-up. We identified 8.3 and 14 kPa as the fibrosis >/=F2 and cirrhosis cut-offs, respectively: their sensitivities were 85.2%/78.3%; specificities 90.7%/98.2%; positive predictive values 93.9%/97.8%; negative predictive values 78.8%/81.6%; diagnostic accuracies 87.3%/88.2%. FibroScan performed better than the other surrogate markers of fibrosis (P < 0.001). Other than fibrosis, other factors independently associated with liver stiffness were ALT for all patients and chronic hepatitis patients (P < 0.001), and 12-month persistently normal ALT (biochemical remission, P < 0.001) in cirrhotics. In patients with biochemical remission either spontaneous or after antiviral therapy (48 of 228, 21%), liver stiffness was lower than in patients with identical fibrosis stage, but elevated ALT (P < 0.001). The liver stiffness dynamic profiles paralleled those of ALT, increasing 1.3- to 3-fold during ALT flares in 10 patients with hepatitis exacerbations. Liver stiffness remained unchanged in 21 with stable biochemical activity (P = 0.001). In conclusion, transient elastography is a new liver parameter that behaves as a reliable surrogate marker of fibrosis in chronic viral hepatitis patients, provided that its relationship with major changes of biochemical activity is taken into account.

Horse antilymphocytic globulin in hepatitis B exacerbation after bone marrow transplantation adoptive immunity transfer.

We describe the case of a HBsAg+, HBeAg+ carrier, treated with lamivudine, who experienced exacerbation of hepatitis after BMT from an anti-HBs+, anti-HBc+, anti-HBe+ donor. The serological profile of the donor and the timing of exacerbation suggested that the adoptive immunity transfer played a major pathogenetic role. Antilymphocyte globulin administration resulted in resolution of hepatitis and seroconversion to anti-HBs+. Therapy aimed at blocking the effector arm of liver damage could represent a novel approach to avoid the risk of progression to fulminant hepatitis without hampering the chances of recovery from hepatitis B.

Molecular analysis of V(H)I+ B lymphocytes in hepatitis C patients.

BACKGROUND AND AIMS: Hepatitis C virus infection is often associated with lymphoproliferative disorders such as essential mixed cryoglobulinemia and B-cell non-Hodgkin lymphoma, which show preferential expression of VHI family products. By analyzing immunoglobulin heavy chain usage, we addressed the question of whether or not clonal B-cell expansion occurrs in patients free of essential mixed cryoglobulinemia or non-Hodgkin lymphoma. PATIENTS AND METHODS: Four hepatitis C virus-positive patients, all undergoing liver transplantation, were studied. Peripheral blood, intra-hepatic, and lymph node lymphocytes were used as a source of B cells. A patient with hepatocellular carcinoma and fresh blood from four healthy donors were used as negative controls. VHI family sequences were cloned and analyzed by reverse transcription-polymerase chain reaction. RESULTS: Immunoglobulin heavy chain sequences from clonally expanded B lymphocytes were identified in three out of four hepatitis C virus-infected patients. The clonally expanded B lymphocyte populations showed a broad spectra of immunoglobulin heavy chain gene usage. CONCLUSIONS: HCV infection can induce B-cell expansion with larger clonal variation. The restricted V gene usage in hepatitis C virus-associated non-Hodgkin lymphoma suggests that there may be selection mechanisms to develop non-Hodgkin lymphoma from non-malignant, clonally expanded B-cell populations in hepatitis C virus-infected patients.

Increasing serum levels of IgM anti-HCV are diagnostic of recurrent hepatitis C in liver transplant patients with ALT flares.

Recurrent hepatitis and acute rejection share common features which make difficult for diagnosis in liver transplant hepatitis C virus (HCV) positive patients. We studied the usefulness of quantitative monitoring of HCV RNA and immunoglobulin (Ig)M anti-HCV in the differential diagnosis between recurrent hepatitis and acute rejection in 98 consecutive anti-HCV positive liver transplant patients. Aminotransferase levels, serum HCV RNA and IgM anti-HCV were measured at the time of transplantation and monthly thereafter. A liver biopsy (LB) was obtained when serum aminotransferase levels increased to twice or more than normal. During a mean follow-up of 16 months 86 aminotransferase flares were observed. Histology was compatible with recurrent hepatitis C in 44 cases and with acute rejection in 28, doubtful in 14. The fluctuations of HCV RNA serum levels were not significantly different in the three groups. Serum IgM anti-HCV levels increased (from negative to positive or with value variations > or = 0.18) in 36 of 44 cases with recurrent hepatitis C at the time of alanine aminotransferase (ALT) flare. IgM anti-HCV remained unchanged in all rejection cases (P < 0.001), but increased in 10 of 11 histologically doubtful cases that were diagnosed as hepatitis at the second LB. Increasing serum levels of IgM anti-HCV at the time of ALT flares are significantly associated with recurrent hepatitis C in liver transplant patients. The quantitative monitoring of IgM anti-HCV appears to be an additional diagnostic tool for distinguishing recurrent hepatitis C from acute graft rejection with a 100% specificity; 100% positive predictive value and 88.9% diagnostic accuracy.

RT-PCR method to quantify vascular endothelial growth factor expression.

The vascular endothelial growth factor (VEGF) is implicated in the progression of cancers. Its expression is well correlated with tumor growth and metastases. The availability of a rapid and sensitive method to detect the amounts of VEGF mRNA in biological samples of limited size, very small biopsies, or samples containing relatively few cells could provide an interesting prognostic tool for clinicians. We have developed an RT-PCR method that allows us to detect the VEGF mRNA from as little as 3 micrograms total mRNA. We have also shown that this protocol can be generalized to all cell lines tested. This method constitutes a very potent tool for the analysis of VEGF mRNA expression in different contexts.

The impact of hepatitis B virus (HBV) and hepatitis C virus (HCV) : from research to clinical practice.

Hepatic carcinogenesis is a complex process that involves profound alterations of the hepatocyte genome (1,2) and has been graded in three stages: induction, promotion, and progression in the animal models (3-5). In recent years, the use of molecular biology techniques have improved significantly the understanding of the mechanisms (alteration of gene and gene expression) that occur during the different steps of carcinogenesis.

Treatment of patients with chronic hepatitis C and cirrhosis.

The most cost effective strategy for antiviral therapy of chronic hepatitis C is the earliest identification and treatment of patients at risk of developing life-threatening complications such as hepatocellular carcinoma. Liver fibrosis represents the best predictor of unfavourable outcome. However, some patients with liver fibrosis already have a histological diagnosis of cirrhosis and there is a debate about whether alpha interferon is still effective in lowering the risk of disease progression in such patients. We identified some of the reasons that may explain seemingly contradictory results of studies addressing this issue. A major cause appears the beginning of follow-up at different starting points during the course of clinically compensated cirrhosis. Some investigators recruited patients because of anti-HCV positivity and elevated transaminases and found cirrhosis only at histology, whereas others recruited patients because cirrhosis had been diagnosed. Ultrasonographic signs of portal hypertension appear to be a useful tool to distinguish the two phases of the disease. Another important cause of reduced response rate to antiviral therapy is the presence of cofactors of liver disease and hepatocellular carcinoma such as present or past HBV infection. Early phase cirrhotics without cofactors appear to benefit most from therapy with a significant lower risk for hepatocellular carcinoma than untreated controls. The therapeutic decision in these patients could be the same as in patients with chronic hepatitis C without cirrhosis. In contrast, the efficacy of interferon remains questionable in HCV patients who already have ultrasonographic signs of portal hypertension and/or past or present HBV coinfection. Prospective, randomized clinical trials should be performed after stratification of these patients for stage and cofactors of liver disease.

Measles IgM immunoreactivity in patients with inflammatory bowel disease.

AIM: The purpose of our study was to examine measles IgM immunoreactivity in patients with inflammatory bowel disease. PATIENTS AND METHODS: In an International collaborative study, serum measles IgM immunoreactivity was assayed in consecutive outpatients with Crohn's disease (n = 95), ulcerative colitis (n = 79), viral hepatitis (n = 63) and blood donors (n = 30). Two commercial measles assays--enzyme linked immunosorbent assay and indirect fluorescence assay--and a Public Health Laboratory Service (PHLS) "in house" antibody capture radioimmunoassay were used. Results were compared with serum rubella and Epstein-Barr virus-specific IgM immunoreactivity, total serum IgM, and measles IgG immunoreactivity. Twenty patients with inflammatory bowel disease were studied serially over a 4-month period. RESULTS: By enzyme linked immunosorbent assay, the prevalence of raised serum measles IgM immunoreactivity was significantly greater in patients with Crohn's disease 23/95 (24%) and ulcerative colitis 20/79 (27%) compared with hepatitis patients 2/63 (3%) and normal controls 0/30 (0%) (p < 0.001). Indirect fluorescence assay produced significantly more positive results than enzyme linked immunosorbent assay in both Crohn's disease (50/87; 57%) and ulcerative colitis (35/68; 51%) but not in controls (0%) (p < 0.001). In contrast, no sera were positive using MCRIA. In the enzyme linked immunosorbent assay, measles IgM immunoreactivity did not correlate with either total IgM, rubella or Epstein-Barr virus IgM immunoreactivities-which were not raised-measles IgM immunoreactivity, or disease activity. Patients not receiving steroids were more likely to have raised measles IgM immunoreactivity (p < 0.5). All sera tested for Rheumatoid factor were negative. Of 20 patients with inflammatory bowel disease studied by ELISA over a 4-month period, 50% showed raised measles IgM immunoreactivity at some stage. CONCLUSION: The data suggest a specific and fluctuating immune response to measles virus in patients with Crohn's disease and ulcerative colitis, that may be modified by corticosteroid therapy.

Amantadine hydrochloride decreases serum ALT activity without effects on serum HCV-RNA in chronic hepatitis C patients.

BACKGROUND AND AIMS: To investigate the effects and tolerance of amantadine in chronic hepatitis C patients. PATIENTS AND METHODS: Forty consecutive patients, with biopsy proven chronic active hepatitis, were treated with amantadine 200 mg daily in the morning for two months. Nineteen patients were previous non responders to alpha-interferon, nine patients experienced hepatitis relapse after interferon treatment, and twelve patients had never been treated with antiviral drugs. Complete blood count, liver and renal function tests were performed two months before, at baseline, end of therapy and two months after its completion. RESULTS: None of the patients experienced significant side effects. Twenty-four patients (60%) showed a reduction of serum aminotransferase levels (twelve patients > 30% and twelve patients < 30% of their basal levels). The analysis of variance showed a significant reduction in aminotransferase levels at the end of treatment (F = 11, p < 0.0001). In four patients, aminotransferases returned to normal, but none of them cleared HCV-RNA. After the end of treatment, serum ALT returned to baseline values in all patients. CONCLUSIONS: Amantadine is well tolerated in chronic hepatitis C patients. The time-relation between therapy and reduction of serum aminotransferase levels in 60% of patients suggests a potential anti-inflammatory activity of the drug without an effect on viraemia.

The prevalence of hepatitis C virus types in patients of the same geographic area, according to the source of infection and liver disease.

BACKGROUND: The duration and stage of hepatitis C might be associated with the source of infection and hepatitis C virus (HCV) types. OBJECTIVE: We studied the relationship among the different HCV types, source, duration, and stage of infection in 100 patients from the Apulia, southern Italy, selected from consecutive clinical records. They were 20 parenterally infected haemophiliacs with 10-20 years of disease history, but without cirrhosis; 20 patients (matched for sex, age and disease) and without known risk factor for parenteral infections; 60 patients with community acquired infection (ten with CAH and ten with cirrhosis with less than 20 years disease history; 20 with cirrhosis and hepatocellular carcinoma (HCC) and more than 20 years of liver disease and 20 matched cases with cirrhosis without HCC). RESULTS: Type 1 and 2 HCVs had comparable prevalence in patients with long lasting and recent HCV infection, 56 and 64%, 26 and 30% respectively. HCV type 3 was found in 6.5-12% of the patients with recent HCV infection, but it was not detected in those with infection longer than 20 years. Type 1 b HCV was more frequently found in HCC patients (68% of cases) than in the other forms of liver disease. The opposite was observed for HCV types (2 and 3). CONCLUSIONS: The prevalence of the different HCV types appears associated with the source and duration of the infection. The interesting association between HCV type 1 b and HCC prompts further studies in larger series of patients.

IgM antibody against measles virus in patients with inflammatory bowel disease: a marker of virus-related disease?

OBJECTIVE: Viral infections of the mesenteric microvascular endothelium have been hypothesized as pathogenetic factors in inflammatory bowel diseases. The aim of this study was to determine whether immunoglobulin M (IgM) antibody against measles virus is associated with disease. PATIENTS AND METHODS: The IgM antibody was detected by indirect antibody test in 36 patients with evidence of Crohn's disease (23 males and 13 females, median age 40 years, range 20-66), 22 patients with ulcerative colitis (14 males and 8 females, median age 42 years; range 19-65), 59 patients with a chronic active hepatitis (35 males and 24 females, median age 56 years, range 38-77) and 30 blood donors (20 males and 10 females, median age 45 years, range 29-62). RESULTS: Twenty-eight of 36 patients (78%) with Crohn's disease and 13 of 22 patients (59%) with ulcerative colitis tested positive as compared to only 3 of 89 (3.3%) controls (P < or = 0.001). CONCLUSION: The detection of IgM anti-measles virus in the majority of patients with Crohn's disease and in about half of ulcerative colitis patients as compared to a very low prevalence in patients with other chronic inflammatory disease is consistent with the hypothesis that the measles virus has pathogenetic implications in inflammatory bowel diseases.

Preoperative serum levels of wild-type and hepatitis B e antigen-negative hepatitis B virus (HBV) and graft infection after liver transplantation for HBV-related hepatocellular carcinoma.

Allograft infection in hepatitis B surface antigen (HBsAg)-positive patients undergoing liver transplant (OLT) is still significant, despite post-transplant prophylaxis with high doses of immunoglobulin to HBsAg. Baseline status and post-OLT levels of viraemia and wild-type and hepatitis B e antigen (HBeAg)-negative hepatitis B virus (HBV) were correlated with the clinical course of 16 consecutive HBsAg carriers. positive for hepatitis B e antibody, with hepatocellular carcinoma who underwent OLT and received permanent post-OLT prophylaxis with antibody to HBsAg (HBsAb). Fourteen patients had less than 10(3) HBV genome equivalents ml(-1) (eq ml[-1]) at baseline and remained HBV free after a median of 36 months following OLT. Two patients with mean pre-OLT viraemia higher than 10(5) genome eq ml(-1) and prevalent HBeAg-negative HBV viraemia before OLT suffered a severe graft hepatitis. Interferon-alpha2b (3 MU m(-2) per day) was able to reduce viraemia in both patients and to revert the clinical course of the infection in one, who remained infection-free 22 months after IFN treatment. Fourteen patients had less than 10(3) HBV genome eq ml(-1) at baseline and remained HBV free, after a median of 36 months following OLT, with permanent HBsAb immunoprophylaxis. These observations suggest that the quantitative analysis of HBV pre-OLT viraemia levels may provide a very useful tool for predicting the ideal time of liver replacement. Clinical trials on the use of antiviral drugs capable of inhibiting HBV serum levels before liver transplantation should be pursued on this premise.

Intrahepatic expression of c-fos, c-myb and c-myc oncogenes: correlation with virus-induced chronic liver disease and response to interferon.

BACKGROUND & AIMS: Oncogenes were activated in experimental models of hepatocyte regeneration. We studied the intrahepatic expression of c-fos, c-myb and c-myc protooncogenes in 117 patients with chronic liver disease: 12 with hepatitis B, 15 HBsAg carriers, 73 with hepatitis C and 17 with non-viral liver damage. METHODS: Oncoproteins were detected by indirect immunofluorescence using high affinity and monoclonal antibodies. Grade and stage of liver damage were measured by numerical score. RESULTS: Nuclear c-fos and/or c-myb were found in 7 (58.3%) hepatitis B patients, in 38 (52%) hepatitis C patients, in 1 (6.6%) HBsAg carrier (p < 0.004) and in none of the non-viral disease patients (p < 0.0001). In no case was c-myc detected. Oncoproteins were correlated with the histological activity index (p < 0.0001) and its components: lobular degeneration and periportal necrosis (p < 0.0001), fibrosis (p < 0.005) and portal inflammation (p < 0.03). Thirty-one chronic hepatitis C patients were treated with alpha-IFN: 9 out of 14 oncoprotein-positive patients (64%) were non-responders, 5 (36%) relapsed and none was a sustained responder. Conversely 9 out of 17 (53%) oncoprotein-negative patients, including 3 patients with histologically active cirrhosis, showed long-term response (p < 0.005). CONCLUSIONS: Intrahepatic c-fos and c-myb were detected in chronic viral hepatitis patients, but not in non-viral liver diseases. Their expression correlated with the grade and stage of liver disease and with poor response to alpha-IFN.