¿Qué papel juega la respuesta humoral en el trasplante hepático?: Realidad o ficción / No disponible

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Reconsidering the H&E stain as the gold standard in assessing the depth of burn wounds.

While histological examination is considered by most as the gold standard for burn depth assessment, it has no practical use in the clinical setting. It has, however, been used in the research setting, as a mean for evaluating emerging techniques of depth measurement. Due to the limitations of the H&E stain, other stains have also been explored, such as lactate dehydrogenase (LDH), as presented in this issue, in "Improving the Histologic Characterization of Burn Depth." As the determination of burn depth is not a typical subject in dermatopathology, a summary of selected techniques and the possible role for the LDH stain in future research, is described herein.

Synergistic effect of PEGylation and pentoxifylline addition on immunoprotection of pancreatic islets.

In this study, a method is proposed to reduce immunological response of immune system against Langerhans islets by PEGylation of islets combined with adjuvant therapy. For this purpose, the best composition for a mixture of succinimidyl valeric acid activated mPEG (mPEG-SVA) with different molecular weights (MWs) and for a mixture of succinimidyl carbonate activated mPEG (mPEG-SC) with different MWs was determined separately. Then, the effect of pentoxifylline (PTX) as an adjuvant drug on immunological response against PEGylated islets at best mPEG composition was studied. The extent of mPEGs reaction, the amount of interlukin-2 (IL-2) and perforin secretion, and the viability of lymphocytes and islets in homo and co-cultures in the presence of PTX at different concentrations were considered for the in vitro evaluation of the proposed method. It was found, that a mixture of mPEG-SVA with MWs of 10 and 5 kDa at a composition of 75 and 25%, respectively, was the best formulation. Also, the addition of PTX drug to co-culture medium increased the protection of PEGylated islets against immune system and a concentration of 75 µg mL-1 of PTX was suitable for islet protection with no adverse effect on immune cells.

Donación en asistolia no controlada: necesidad, oportunidad y reto / Uncontrolled non-heart beating donation: need, opportunity and challenge

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Código alfa. Inicio de un nuevo programa de donación en asistolia / Alpha code. The start of a new non-heart beating donor program

Objetivo: Presentar resultados iniciales de un programa de donación en asistolia (DA) en unaciudad de menos de 500.000 habitantes. Diseño: Estudio observacional prospectivo durante 2010 y 2011.Ámbito: Hospital Virgen de las Nieves y Área Metropolitana de Granada. Población: DA y donantes en muerte encefálica (DME) de la provincia de Granada en 2010 y2011.Variables de interés: Características de los DA, tiempos extrahospitalarios e intrahospitalarios, negativas familiares y judiciales, métodos de preservación, procedimiento de información a familiares. Órganos: causas de no validez, extraídos y trasplantados. Receptores: sesiones de hemodiálisis y creatinina al alta. DME: número de donantes reales (DR) y de trasplantes renales. Resultados: En ME hubo 102 DR y se realizaron 104 trasplantes renales. Se han registrado en asistolia 22 donantes potenciales (DP), 21 donantes elegibles (DE), 20 DR y 13 donantes utilizados(DU). Edad media de los DR: 50 años (rango 33-62), 16 hombres y 4 mujeres. Se han realizado21 trasplantes renales y 2 hepáticos de DA. Las causas de no validez son múltiples. Número medio de sesiones de hemodiálisis postrasplante: 1,4 (rango 0-6). Estancia hospitalaria media:25 días (rango 14-41). Creatinina media al alta: 3,4 mg/dL (rango 1,5-6,4). Ninguna negativa judicial y una negativa familiar. Se describen los métodos de preservación y el procedimiento de información a familiares. Conclusiones: Los resultados iniciales apoyan el desarrollo de programas de DA en ciudades de menos de 500.000 habitantes. La DA ha supuesto en 2011 el 20,19% de los trasplantes renales y el 19,6% de los donantes de órganos de la provincia de Granada (AU)

Objective: To present the preliminary results of a non-heart beating donor (NHBD) program in a city of under 500,000 inhabitants. Design: A prospective observational study was conducted between 2010 and 2011.Setting: Virgin de las Nieves Hospital and metropolitan area of Granada (Spain).Population: NHBD and brain dead donors (BDD) in the province of Granada during 2010 and2011.Study variables: Characteristics of NHBD, out- and in-hospital times, family and legal refusals, preservation methods, and family information procedure. Organs: reasons for organnon-validness, and harvested and transplanted organs. Recipients: hemodialysis sessions and creatinine at discharge. BDD: number of real donors (RD) and of kidney transplants. Results: Among the BDD there were 102 RD and 104 kidney transplants were carried out. In systole, 22 potential donors, 21 eligible donors, 20 RD and 13 used donors were registered. The mean age among the RD was 50 years (range 33-62)(16 males and 4 females). Twenty-onekidney and two liver transplants from NHBD were performed. There were a number of reasons for organ non-validness. The mean number of post-transplantation hemodialysis sessions was1.4 (range 0-6). The mean hospital stay was 25 days (range 14-41), and the mean creatinine concentration at discharge was 3.4 mg/dl (range 1.5-6.4). There was one family rejection and no legal (court-ruled) rejections. The preservation methods and family information procedure are described. Conclusions: The preliminary results support the development of NHBD programs in cities with under 500,000 inhabitants. In 2011, NHBD accounted for 20.19% of the kidney transplants and19.60% of the global organ donations in the province of Granada (AU)

[Trying to unravel an unresolved issue in regenerative medicine: gene expression profiling of MSCs]. / Genexpressionsmuster mesenchymaler Stammzellen: ein ungelöster Aspekt in der regenerativen Medizin.

BACKGROUND: Mesenchymal stem cells (MSCs) are adult fibroblastoid progenitor cells. Because of their immunoregulatory properties and their so-called trophic effects, MSCs play an important role in tissue regeneration, inflammation and trauma. Tissue trauma and challenge, for example during radiotherapy or infection, result in the release of so-called "danger molecules", which may be derived from dying cells or incoming pathogens. The molecular response of MSCs to this tissue stress remains largely elusive. MATERIAL AND METHODS: In this study we examined the cell biological response of MSCs derived from human parotid glands (pgMSCs) and used bacterial endotoxin as a model of tissue stress and inflammation. PgMSCs from 3 donors were isolated, expanded and tested for classical tri-lineage plus myogenic differentiation. The cell biological response to the model "stressor" endotoxin was examined by low density gene expression arrays. RESULTS: Through immunofluorescence and immunohistochemistry we were able to proof osteogenic, adipogenic, chondrogenic, and myogenic differentiation potential characteristic for stem cells. In vitro, gene expression analysis showed a characteristic modulation of MSCs after stimulation with endotoxin Lipopolysaccharide (LPS). Specifically, receptors and ligands typically involved in immune regulation, such as interleukins, TGF-ß, tumor necrosis factors (TNF), and toll-like receptors (TLR), were regulated. CONCLUSION: Our study elucidates some key functions and molecules, which are regulated in MSCs during tissue stress and inflammation. A thorough understanding of their cell biological function will aid future rationale therapeutic application of MSCs.

Viabilidad de los donantes a corazón parado y capnografía / Feasibility of donors-after-cardiac-death and capnography

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Improving posttransplantation survival of human ovarian tissue by treating the host and graft.

OBJECTIVE: To improve posttransplantation survival of frozen-thawed human ovarian tissue in immunodeficient mice. DESIGN: Histologic study of transplanted human ovaries after treating the host and graft. SETTING: Infertility unit, university-affiliated tertiary medical center. PATIENT(S): Ovarian tissue from six girls/women (aged 5-23 years) who had undergone ovarian laparoscopy for fertility preservation. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Thawed ovarian samples were transplanted into the back muscle of immunodeficient mice divided into four groups: A) no treatment; B) host treatment with vitamin E and gonadotropins before and after grafting; C) graft incubation with vascular endothelial growth factor A (VEGF-A) and vitamin E before transplantation; and D) host as in B, graft as in C. Ungrafted thawed samples served as control. Assessment of graft survival was conducted by follicle counts, apoptosis evaluation, immunohistochemical stainings for proliferating cell nuclear antigen (PCNA) and VEGF-A expression. RESULT(S): Only grafts incubated before transplantation (groups C and D) retained their original size. Follicle number was low in all grafts. PCNA expression was found in most grafts. Apoptosis was significantly lower in the untreated and treated grafts transplanted into treated hosts (groups B and D) than in ungrafted-thawed samples and group A grafts. All grafted groups had significantly higher expression of VEGF-A than ungrafted-thawed samples. CONCLUSION(S): Survival of transplanted human ovarian tissue may be improved by treatment of the host and graft. Further studies to evaluate treatments with a potential benefit in human ovarian autotransplantation are needed.

Recomendaciones para la indicación, obtención, procesamiento y evaluación de biopsias en el trasplante renal / No disponible

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Recent advances in pig-to-human organ and cell transplantation.

Xenotransplantation using pigs offers the prospect of an unlimited number of organs and cells for clinical transplantation. A major step forward has been achieved with the introduction of pigs homozygous for alpha1,3-galactosyltransferase gene-knockouts that do not express the major antigenic target for primate antipig antibodies (i.e., Galalpha1,3Gal). Heterotopic heart transplants have survived for 2-6 months in baboons. However, other immune and pathophysiologic barriers remain, including: i) anti-non-Gal antibodies and cells of the innate immune system; and ii) thrombogenesis associated with incompatibilities in the coagulation-anticoagulation systems of pig and primate. Further genetic modification of the organ-source pig to overcome these barriers is being undertaken.

Análisis de supervivencia de los carcinomas de células renales órgano-confinados. Valor pronóstico de la clasificación TNM 1997 / Survival analysis for localized renal cell carcinoma. Prognostic value of 1997 TNM classification

Introducción: En la 5ª edición de la clasificación TNM de 1997 para tumores renales se modificó el punto de corte del tamaño del tumor primario para los estadios I y II, permitiendo una mejor agrupación de pacientes con distinta supervivencia. Sin embargo, dada la variable evolución del carcinoma de células renales determinada por su agresividad biológica, se cuestiona la utilidad del tamaño tumoral como elemento pronóstico y de estadiaje. Se realiza un estudio de supervivencia del carcinoma de células renales para valorar si la nueva clasificación TNM para el estadio I y II es la que mejor predice la supervivencia basándose en el tamaño del tumor. Material y Método: Se ha realizado un estudio retrospectivo de 158 carcinomas de células renales intervenidos en nuestro hospital en un periodo de 12 años. Se ha creado una base de datos con variables clínicas debidas al paciente y al tumor, y se ha valorado estadio patológico, grado nuclear y supervivencia causa específica, centrándonos en los estadios I y II. Resultados: Según la categoría pT obtuvimos 27 pT1 (17,08%), 52 pT2 (32,91%), 45 pT3A (28,45%), 10 pT3B (6,32%), y 24 pT4 (15,18%). La supervivencia tumor-específica a los 5 años para pT1-pT2, estadio I-II, es de 100% y 94% respectivamente, sin encontrar diferencias estadísticamente significativas entre los estadios I y II (log-rank test 0,53, p no significativa). La supervivencia tumor-específica a los 5 años para la categoría pT3A, pT3B, y pT4 es de 76,5%, 66,6% y 38,4%. Encontrando una diferencia en la supervivencia estadísticamente significativa según la localización del tumor primario intrarrenal (T1 y T2) y la extrarrenal (T3A, T3B, T4) (log-rank test 9,06, p < 0.05). Para pT1 y pT2 no se encuentran diferencias estadísticamente significativas según el grado nuclear (test exacto de Fisher, p=1). Comparando la relación entre estadio pT y grado nuclear del tumor primario obtenemos un valor para X2 de tendencia lineal de 38,19, p<0.001. Conclusiones: Las diferencias en la evolución del carcinoma de células renales órgano-confinado según el tamaño tumoral pueden ser debidas a la existencia de otras variables biológicas y moleculares, posiblemente asociadas al estadio, que no se controlan en los estudios. La clasificación TNM en los carcinomas de células renales órgano-confinados basándose en el tamaño del tumor nos parece artificiosa. Son necesarias nuevas revisiones del sistema de clasificación para identificar qué grupo de pacientes con carcinoma de células renales órgano-confinado va a presentar evolución desfavorable e incluirlos en una categoría distinta

Background: the 5th edition of TNM classification for renal cell carcinoma changed the cut-off point of the tumor size for localized tumors, achieving a better distribution of patients with similar survival. Nevertheless, because of the variable evolution of renal cell carcinoma, the prognostic significance of tumor size is questioned as a staging criterion in organ-confined renal cell carinoma. We analyse renal cell carcinoma specific survival and the prognostic significance of tumor size in I and II stage. Methods: We made a retrospective study with 158 renal cell carcinoma surgically treated in our hospital along 12 years. It was created a data base with clinical variables from patient and tumor and analyzed pathological staging, nuclear grade and specific survival, overall stage I and II. Results: 27 renal cell carcinoma were pT1 (17.08%), 52 pT2 (32.91%), 45 pT3A (28.45%), 10 pT3B (6.32%), y 24 pT4 (15.18%). The specific survival at 5 years for pT1-pT2, I-II stage, was 100% and 94% respectively, and no statistic significant differences were found between stage I and II (log-rank test 0.53, p>0.05). The specific survival at 5 years for pT3A, pT3B, y pT4 was 76.5%, 66.6% y 38.4%. There was a significant difference in survival in accordance with the tumor location, intrarenal (T1 y T2) versus extrarenal (T3A, T3B, T4) (log-rank test 9.06, p< 0.05). According to nuclear grade we don’t find significant differences for pT1 y pT2 (Fisher test, p=1). Regarding the relation between pT stage and nuclear grade of the tumor we obtained a X2 inear tendency of 38.19, p<0.001. Conclusion: The differences in the evolution of the organ-confined renal cell carcinoma with respect to the tumor size may be due to other molecular and biological variables, probably associated with stage. not controlled in essays. The TNM classification for organ-confined renal cell carcinoma based in tumor size seems artificial. New revisions of the classification system are necessary to identify which organ-confined carcinoma will have unfavourable evolution and to include them in a different category

Hyperacute rejection of mouse lung by human blood: characterization of the model and the role of complement.

BACKGROUND: The pathophysiology of hyperacute lung rejection (HALR) is not fully understood. A mouse model of HALR by human blood would be valuable to efficiently dissect the molecular mechanisms underlying this complex process, but it has not been described. METHODS: We developed a xenogenic mouse lung-perfusion model. Perfusion with heparinized autologous blood (n=3) was compared with human blood unmodified (n=7) or pretreated with C1 inhibitor (n=5) or soluble complement receptor type 1 (n=6) at unchanged flow conditions. RESULTS: Perfusion with autologous blood was associated with stable physiologic parameters and no overt evidence of lung injury for up to 2 hr. Pulmonary artery perfusion pressure increased rapidly after introduction of unmodified human blood, plasma anti-Gal(alpha)1,3Gal antibodies declined (90% immunoglobulin [Ig]M, 80% IgG), and lungs reliably met survival endpoints within 11 min (median 10 min, confidence interval [CI]: 9-11). Human Ig and neutrophils were rapidly sequestered in the lung. Survival was significantly prolonged in the soluble complement receptor type 1 group (36 min, CI: 26-46) (P<0.01) and in the C1 inhibitor group (23 min, CI: 21-25) (P<0.05), and pulmonary vascular resistance elevation and complement activation were significantly attenuated but not prevented. CONCLUSIONS: Hyperacute rejection of mouse lung by human blood occurs with kinetics, physiology, and histology closely analogous to the pig-to-human model. In addition, as in that model, neither of two potent soluble-phase complement inhibitors prevented complement activation or HALR. We conclude that the mouse lung model is relevant to dissect the cellular and molecular mechanisms governing HALR.

Clinical xenotransplantion--how close are we?

CONTEXT: Xenotransplantation with pig organs offers a medium-term solution to the shortage of organs available for clinical transplantation. The immunological barriers to xenotransplantation have been, and remain, formidable. In the early 1990s, the identification of Galalpha1,3Gal (Gal) as the main target for human xenoreactive (anti-pig) antibodies and the development of pigs transgenic for a human complement regulatory protein, decay-accelerating factor (hDAF), were major advances. The presence of hDAF on the vascular endothelium of pig organs provided some protection against complement-mediated hyperacute rejection. This protection, however, was short-lived, and, until recently, the longest median time for organ survival that had been achieved (with combinations of biological and pharmacological immunosuppressants) in a series of pig-to-primate organ transplants was under a month. STARTING POINT: Christopher McGregor and colleagues recently reported to the International Society of Heart and Lung Transplantation (J Heart Lung Transplant 2003; 22: S89) that, by combining the use of organs which express hDAF with the administration of a soluble Gal glycoconjugate and other immunosuppressive agents, the survival of pig hearts in baboons can be extended to a median of 76 days. McGregor's work suggests that immunological barriers to xenotransplantation are not insurmountable. WHERE NEXT? The recent generation of pigs that do not express Gal epitopes (alpha1,3-galactosyltransferase gene-knockout pigs) might remove the need both for the expression of hDAF and the administration of a soluble Gal glycoconjugate. The absence of a natural antibody response will allow investigation of the cellular immune response and of any molecular incompatibilities between pig and primate that may be detrimental to graft survival. Furthermore, the absence of a humoral response may open the way for the induction of immunological tolerance (or unresponsiveness in the absence of exogenous immunosuppression) to a transplanted pig organ.