RESUMEN
INTRODUCTION: The aim of this study was to assess efficacy and safety of sirolimus (SIR) in heart transplant recipients to prevent further development of coronary artery disease (TxCAD) already confirmed by using coronary angiography. MATERIAL AND METHODS: We performed a retrospective case-control study involving all 60 heart transplant recipients receiving SIR in a number of combinations with other immunosuppressive drugs, and 60 matched individuals after heart transplantation treated without SIR. TxCAD was diagnosed using elective coronary angiography in 9 subjects in the study group (8 males and 1 female) of mean age 44 +/- 11 years, including ischemic cardiomyopathy in 4 members. The control group of 15 individuals 15 males of mean age 47 +/- 7 years, including ischemic cardiomyopathy in 8. We compared time to develop significant TxCAD and death caused by TxCAD, and all-cause deaths. Significance was assessed using log-rank and chi-square tests, when applicable. RESULTS: Significant TxCAD (critical coronary lesions, myocardial infarction or death) was observed in 5 (56%) patients receiving SIR and 11 (73%) without SIR (P = not significant [NS]). Time to develop significant TxCAD was comparable. There were 2 (22%) deaths in the SIR group and 8 (53%) in the control group (P = NS). Survival time was significantly longer among subjects receiving SIR (P = .02). None of deaths in the study group was caused by TxCAD compared with 6 (40%) deaths among controls (P = .09). Time of freedom from death caused by TxCAD was significantly longer in the study group (P = .023). CONCLUSION: SIR prolonged survival in heart transplant recipients with TxCAD confirmed using coronary angiography.
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Enfermedad Coronaria/inmunología , Enfermedad Coronaria/cirugía , Trasplante de Corazón/inmunología , Sirolimus/uso terapéutico , Adulto , Estudios de Casos y Controles , Angiografía Coronaria , Enfermedad Coronaria/diagnóstico por imagen , Muerte , Trasplante de Corazón/mortalidad , Humanos , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/diagnóstico por imagen , Complicaciones Posoperatorias/inmunología , Estudios Retrospectivos , Análisis de Supervivencia , Sobrevivientes , Adulto JovenRESUMEN
INTRODUCTION: Hyperglycemia intensifies nonenzymatic glucose coupling to tissues, resulting in myocardial stiffness and formation of advanced glycation end products (AGE). The aim of this study was to assess seeking AGE in the myocardium from patients with type 2 diabetes (DM2) subjected to orthotopic heart transplantation (OHT), seeking to establish whether AGE play a role in the development of cardiomyopathies leading to OHT. MATERIAL: The 2 studied groups consisted of 11 hearts explanted from patients with ischemic cardiomyopathy+DM2 (ICM+DM2, 55 +/- 6.5 years) and 8 from dilated cardiomyopathy+DM2 (DCM+DM2, 49.6 +/- 4.5 years). Comparative subgroups were composed of nondiabetic explanted hearts, 41 with ICM (52.8 +/- 5.8 years) and 41 with DCM (52.7 +/- 4.2 years). All patients were males. METHODS: We examined immunohistochemical localization of AGE using a semiquantitative scale of reaction intensity in cardiomyocytes, fibroblasts, capillaries, arterioles, and arteries. Additionally, we calculated the scores for cardiocytes (AGE(Cardiocyte)) and all left ventricular components (AGE(LV)). RESULTS: The cytoplasmic AGE deposits in cardiomyocytes were predominantly diffuse-granular in DM2 groups, whereas nondiabetic groups showed a lack of a reaction or a diffuse pattern. There were no differences in the reaction intensity between the 2 studied groups, or 2 comparative groups. All myocardial constituents showed higher AGE intensity in DM2 than nondiabetic groups. Only in the ICM+DM2 group did the DM2 duration correlate with AGE staining in selected myocardial layers and with AGE(Cardiocyte) and AGE(LV). CONCLUSIONS: The presence of AGE in the hearts of patients requiring transplantation was related to the duration of DM2. The deposition of AGE in left ventricular myocardium was enhanced by DM2 particularly in patients with ICM.
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Cardiomiopatía Dilatada/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Angiopatías Diabéticas/cirugía , Productos Finales de Glicación Avanzada/fisiología , Trasplante de Corazón/fisiología , Isquemia Miocárdica/epidemiología , Adulto , Arteriolas/fisiopatología , Capilares/fisiopatología , Cardiomiopatía Dilatada/cirugía , Angiopatías Diabéticas/epidemiología , Hemoglobina Glucada/metabolismo , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/cirugía , Miocitos Cardíacos/fisiologíaRESUMEN
INTRODUCTION: Cardiocyte hypertrophy is accompanied by polyploidy, seen as a decrease in chromatin density in the enlarged nucleus. Repeated biopsies of a transplanted heart offer the possibility of a dynamic evaluation of these phenomena. The aim of this work was an evaluation of cardiocyte nuclear chromatin density in transplanted hearts during long-term follow-up. MATERIALS AND METHODS: The material encompassed myocardial biopsy specimens taken during the first week, first month, and then on an annual basis up to 10 years after surgery. Only biopsy specimens with no rejection were considered (grade "0" International Society for Heart and Lung Transplantation [ISHLT] 122 biopsy specimens). The control group consisted of 7 donor heart specimens. We evaluated the optical density-mean gray level-of cardiomyocyte nuclear chromatin. We determined correlations of this index with the nuclear area, and with left ventricle ultrasound measurements, using correlation analysis. RESULTS: The chromatin mean gray level decreased with time, correlating positively with interventricular septum thickness, left ventricle posterior wall diameter, and left ventricular mass. Analysis of individual periods showed a significant positive correlation of the mean grey level with the cardiocyte nuclear surface in year 3, 4, and 9 after transplantation, thereby suggesting the occurrence of polyploidy at those times. The significant negative correlation of these values (1 week and 1 year) indicated normalization of early cardiocyte hypertrophy. CONCLUSIONS: With the passage of time chromatin condenses, leading to pyknosis. The activity of cardiocyte chromatin correlated with left ventricular hypertrophy. Compensatory cardiomyocyte polyploidy is a periodical phenomenon.
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Cromatina/ultraestructura , Trasplante de Corazón/fisiología , Ventrículos Cardíacos/anatomía & histología , Miocitos Cardíacos/citología , Núcleo Celular/patología , Ecocardiografía , Estudios de Seguimiento , Genoma , Tabiques Cardíacos/patología , Trasplante de Corazón/patología , Ventrículos Cardíacos/patología , Humanos , Poliploidía , Complicaciones Posoperatorias/patología , Estudios Retrospectivos , Factores de TiempoRESUMEN
UNLABELLED: The aim of this study was to assess the effects of early thymoglobulin administration on cardiocyte nuclear status in orthotopic heart transplant (OHT) recipients. MATERIAL AND METHODS: We investigated endomyocardial biopsies (EMBs) from 31 OHT recipients and 10 control cases. OHT patients were divided into the standard group who were treated without thymoglobuline; an ATG group who received thymoglobulin electively, and a standard+ATG group who were administered thymoglobulin upon a drop in renal function. We evaluated only EMBs obtained at 1 and 4 weeks after OHT showing no significant rejection (ISHLT grades 0 to 1B). The morphometric studies were performed using a computerized, automated Quantimet image analysis system. Overall, 1750 cardiocyte nuclei were quantitated for area, length, breadth, perimeter, chromatin median grey level, and fullness factor. Statistical analysis was performed using the Mann- Whitney U test, the Wilcoxon test, and discriminant analysis. RESULTS: All OHT groups showed significantly higher values (indicating nucleus enlargement) than the control group. All factors suggesting myocardial hypertrophy were significantly higher in the standard group; however, they decreased significantly with time. In contrast, the nuclear geometric parameters were significantly lower and stable throughout the study in the ATG group. The results of the standard+ATG group were intermediate, and their normalization as incomplete at the week 4 examination. Discriminant analysis revealed the closest Mahalanobis distance between control and ATG groups both at and weeks 1 and 4 after OHT. CONCLUSION: Thymoglobulin administered early after surgery protected cardiocyte hypertrophy in heart transplant recipients, mitigating graft ischemic damage.
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Anticuerpos Monoclonales/uso terapéutico , Cardiomegalia/prevención & control , Trasplante de Corazón/inmunología , Complicaciones Posoperatorias/prevención & control , Suero Antilinfocítico , Biopsia , Cardiomegalia/patología , Trasplante de Corazón/efectos adversos , Trasplante de Corazón/patología , Humanos , Inmunosupresores/uso terapéutico , Miocardio/patología , Periodo PosoperatorioRESUMEN
UNLABELLED: Remodeling taking place in transplanted myocardium leads to a change in the number of cardiocytes. Ultrasound measurements and biopsy evaluation should reflect their loss and compensation. We sought to evaluate the morphology of the transplanted heart upon long-term follow-up. MATERIAL AND METHODS: Myocardial biopsies were obtained in the first week, first month, and then annually for 10 years from transplantation that did not show rejection (grade "0" ISHLT, 122 biopsies). The control group encompassed 7 donor heart fragments. Proliferation in biopsies was evaluated with Ki67 (M7240, DAKO), cardiocyte hypertrophy by measuring their diameter, the surface area of the nuclei, nuclear-sarcoplasmic index, and stromal fibrosis evaluated as the surface area fraction. Ultrasound measurements included diastolic thickness of the interventricular septum, posterior wall of the left ventricle, and left ventricular mass. The correlation of measurements with time from transplantation was evaluated using Spearman's test. RESULTS: A positive Ki67 reaction was observed in fibroblasts and endothelial cells. The increased cardiocyte nuclear area correlated with the time elapsed since transplantation (r = 0.2; P < .05) with a simultaneous decrease in cardiocyte thickness (r = -0.3; P < .05), without changes in the nuclear-cytoplasmic index (r = 0.02; P > .05). Stromal fibrosis also increased (r = 0.1; P < .05). Ultrasound measurements of the left ventricle showed a decreased tendency with the passage of time (r = -0.2 to -0.3; P < .05). CONCLUSION: A transplanted heart does not undergo hypertrophy but rather fibrous atrophy with apparent compensatory hypertrophy of the cardiomyocytes.
Asunto(s)
Trasplante de Corazón/patología , Miocardio/patología , Remodelación Ventricular/fisiología , Biopsia , División Celular , Núcleo Celular/ultraestructura , Diástole , Estudios de Seguimiento , Supervivencia de Injerto , Trasplante de Corazón/inmunología , Humanos , Inmunosupresores/uso terapéutico , Miocardio/inmunología , Miocitos Cardíacos/citología , Miocitos Cardíacos/patología , Estudios Retrospectivos , Retículo Sarcoplasmático/ultraestructura , Factores de Tiempo , Función VentricularRESUMEN
BACKGROUND: Apoptotic mechanisms take place in cardiocyte death during acute heart graft rejection and remodeling by the mitochondrial pathway. This process is suppressed by Bcl-2 protein. Besides that, knowledge about cardiocyte antiapoptotic responses after heart transplantation is scanty. We sought to estimate Bcl-2 expression in the absence of rejection. MATERIAL: The study group included endomyocardial biopsies taken at 1 week, 1 month, 1 through to 10 years after heart transplant, which showed rejection grade "0"; the control group were donor heart fragments. METHOD: Bcl-2 expression was determined immunohistochemically by NP030 antibody (DAKO) and Envision-DAB. The intensity of staining was assessed semiquantitatively. RESULTS: No Bcl-2 expression was seen in the controls; in the posttransplant groups, the significantly strongest sarcoplasmic reaction was observed at 1 week after heart transplant. Thereafter, the reaction decreased, and was weakest in the 3- and 5-year groups. From this time, Bcl-2 expression increased albeit without statistical significance. The intensity of the reaction showed no correlation with the time elapsed from heart transplant (Spearman r = 0.05; P > .05). CONCLUSION: The expression of antiapoptotic Bcl-2 protein occurs during the entire posttransplant period, being probably a preservative and adaptative response.
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Trasplante de Corazón/fisiología , Miocardio/patología , Miocitos Cardíacos/fisiología , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Apoptosis , Biopsia , Estudios de Seguimiento , Supervivencia de Injerto/fisiología , Trasplante de Corazón/patología , Humanos , Inmunohistoquímica , Miocardio/citología , Miocitos Cardíacos/citología , Periodo Posoperatorio , Estudios RetrospectivosRESUMEN
UNLABELLED: Morphometric publications based on the measurement of cardiocyte nuclei indicated their progressive hypertrophy ignoring, however, their shape, which is a deciding factor for the microscopic-based diagnosis of hypertrophy. We sought was to demonstrate how the shapes of cardiocyte nuclei change over time and correlate them with the thickness of the interventricular septum, (IVS) the biopsy site. MATERIAL: We evaluated myocardial biopsies taken in the first week, first month, and then annually until posttransplant year 10. Only biopsies with no rejection were considered: grade "0" ISHLT (122 biopsies). The control group encompassed fragments from seven donor hearts. METHODS: Cardiomyocyte nuclei were evaluated morphometrically. We calculated the length, breadth, perimeter, roundness, elongation, and fullness factors for correlation with the IVS thickness, and selected indices. The relationships between karyometry and IVS thickness (measured by ultrasound) as well as time were calculated by Spearman's correlation test. RESULTS: Among the examined indices, only nuclear length did not correlate significantly with follow-up time. Among the remaining indices, the strongest correlations with time were observed with regard to breadth (r = 0.214), perimeter (r = 0.150), roundness (r = -0.06) and fullness (r = 0.06), and finally elongation (r = 0.02). The decreasing thickness of the interventricular septum (r = -0.31) showed a weak correlation only with the cardiocyte nuclear length (r = -0.05). CONCLUSION: Graft aging imitates hypertrophy inasmuch as cardiocyte nuclei become wider despite the decreased thickness of the interventricular septum. Therefore, karyometric measurements do not reflect myocardial morphology.
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Núcleo Celular/ultraestructura , Trasplante de Corazón/fisiología , Miocitos Cardíacos/citología , Apoptosis , Biopsia , Núcleo Celular/patología , Estudios de Seguimiento , Tabiques Cardíacos/citología , Tabiques Cardíacos/patología , Trasplante de Corazón/patología , Humanos , Miocardio/citología , Miocardio/patología , Miocitos Cardíacos/patología , Periodo Posoperatorio , Estudios Retrospectivos , Factores de TiempoRESUMEN
BACKGROUND: Distribution and staining of the nuclear chromatin are sensitive indicators of changes in physiology and pathology of cells. However, their use in heart transplant recipients is rare. The aim of this study was to compare cardiomyocyte status in heart transplant recipients suffering from moderate acute cellular rejection and subjects without signs of active cellular rejection. MATERIALS AND METHODS: One hundred twenty-nine endomyocardial biopsy samples from 43 heart transplant recipients (no later than 6 months after surgery) were evaluated. Overall, 3235 cardiomyocytic nuclei were analyzed using the Quantimet image analysis system to assess the mean gray level: 1584 nuclei were found in biopsies without signs of rejection or with nonsignificant rejection (ISHLT grades 0, 1A, and 1B), whereas the remaining 1651 nuclei were measured from biopsies showing ISHLT grade 3A (significant rejection). Additionally, the chromatin distribution was assessed in all eligible nuclei. RESULTS: The mean gray level was markedly increased in nuclei from biopsy samples with significant rejection (182.6 vs 112.5, P < .001, Mann-Whitney U test). Moreover, the analysis of chromatin distribution revealed significantly more frequent chromatin marginalization and irregular distribution in rejecting subjects (P < .001, chi-square test). CONCLUSION: Inflammatory stimulation of cardiomyocytes during acute cellular rejection of the transplanted heart influences the chromatin distribution in the nuclei, which may have an additional value, when assessing the severity of rejection.
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Núcleo Celular/fisiología , Cromatina/patología , Rechazo de Injerto/patología , Trasplante de Corazón/patología , Células Musculares/patología , Enfermedad Aguda , Biopsia , Núcleo Celular/ultraestructura , Cromatina/ultraestructura , Válvulas Cardíacas/patología , Humanos , Procesamiento de Imagen Asistido por Computador , Células Musculares/trasplanteRESUMEN
Human aortic, mitral, tricuspid and pulmonary heart valves were investigated by the contact mode atomic force microscopy (AFM) in air, and using FT-IR spectroscopy in the frequency range 950-4000 cm(-1). Heart valves were collected post mortem from 65-78 years old patients who died from non-cardiac diseases. All of the examined valves showed considerable heterogeneity in the surface topography of collagen fibrils as well as in their organization on the tissue surface. The AFM images revealed areas with significantly different spatial organization of the collagen fibril bundles. We observed zones with multidirectional, stacked collagen fibrils as well as areas of thin fibrils packed regularly, densely and "in phase". The majority of the collagen fibrils reproduced the typical transverse D-banding pattern, with the band interval varying in rather wide range of 70-90 nm. Using AFM imaging, objects that correspond to some pathological states of heart valves at their early stages, i.e. some forms of mineral deposits, were observed. The FT-IR spectra allowed us to recognize main components, i.e. collagen and elastin, in di.erent layers (ventricularis, fibrosa) of the valve leaflets as well as they gave also support for the presence of mineral deposits on the valve surface. The presented results showed, that the AFM imaging and FT-IR spectroscopy can be applied as a complementary methods for structural characterization of heart valves at the molecular and supramolecular levels.
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Colágeno/química , Colágeno/ultraestructura , Elastina/química , Elastina/ultraestructura , Válvulas Cardíacas/química , Válvulas Cardíacas/ultraestructura , Anciano , Humanos , Microscopía de Fuerza Atómica , Minerales/química , Complejos Multiproteicos , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
BACKGROUND: The role of BRCA1 in chronic ischemic episodes seems to be pivotal for adverse remodeling and development of ischemic cardiomyopathy, because of its role in DNA repair and apoptosis. The aim of this study was to investigate the role of BRCA-1 in idiopathic dilated cardiomyopathy (IDCM). MATERIAL AND METHODS: The study group (IDCM) comprised myocardial samples from hearts explanted before transplantation owing to IDCM in 10 males (age 44 ± 5.3 years) without clinical symptoms of ischemic heart disease. The control group consisted myocardial fragments taken from 10 male heart valve and pulmonary artery donors with diagnosed cerebral death (age 40 ± 2.3 years). BRCA1 was detected immunohistochemically with rabbit anti-BRCA1 polyclonal antibody. The intensity of BRCA1 expression was semiquantitatively assessed for cardiocytes, small vessels including capillaries, and interstitial cells. The significances between groups were estimated using the Mann-Whitney U test. RESULTS: All IDCM cases were positive and presented nonuniform BRCA1 expression: hypertrophied cardiocytes showed very intense staining and typical cardiomyopathic cardiocytes were stained weakly forming mosaic. Control cases showed weak-to-moderate uniform staining. Intensity of staining was significantly higher in IDCM cardiocytes, whereas small vessels and interstitial were stained similarly in both groups. CONCLUSIONS: IDCM adverse remodeling results in more intense but nonuniform BRCA1 expression. This phenomenon seems to reflect IDCM biology: lower BRCA1 expression in myocytes with lower anti-apoptotic and DNA damage repair activity, with the opposite in hypertrophied myofibers.
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Cardiomiopatía Dilatada/patología , Ubiquitina-Proteína Ligasas/metabolismo , Remodelación Ventricular/fisiología , Adulto , Apoptosis/fisiología , Biomarcadores/metabolismo , Capilares/metabolismo , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Isquemia Miocárdica/patología , Miocardio/metabolismo , Miocitos Cardíacos/metabolismoRESUMEN
INTRODUCTION: Structural modification of proteins, mainly collagen in connective tissues, is important in the manufacture of tissue-derived biomaterials. Natural compounds like genipin or tannic acid (TA) have been proposed instead of glutaraldehyde which shows cytotoxic effects on the processed tissue. Furthermore, calcification of glutaraldehyde-treated tissue limits the functional lifetime of bioprostheses. TA is known to form numerous hydrogen bonds with proteins. The purpose of our study was to investigate structural changes in porcine pericardium upon chemical modification with tannic acid. METHODS: Porcine pericardium tissue (PP) was soaked in 2% TA for 4, 24 or 48 hours. Changes in tissue structure were studied using electrophoresis (SDS-PAGE) and histological examination. Structural stability of PP tissue was evaluated by SDS/NaCl extraction method and enzymatic digestion with pancreatin. RESULTS: TA-modification of PP caused a time-dependent decrease in the number of peptides extracted from tissue. Microscopic studies revealed no significant morphological differences between native and TA-modified tissues, except for the native pancreatin-digested tissue where lack of both cells and low molecular peptides was observed. CONCLUSION: Modification of PP with TA causes the structural changes leading to an increase in the tissue resistance to SDS/NaCl extraction and enzymatic digestion, providing experimental evidence for the higher structural stability of TA-treated tissue.
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Pericardio/efectos de los fármacos , Pericardio/patología , Taninos/farmacología , Animales , Tejido Conectivo/patología , Electroforesis en Gel de Poliacrilamida , Matriz Extracelular/patología , Fibroblastos/metabolismo , Microscopía , Pancreatina/metabolismo , Péptidos/metabolismo , Porcinos , Factores de TiempoRESUMEN
The aim of this study was to compare cardiomyocytes and stromal pathology in heart transplant recipients treated with rapamycin (RAPA) versus cyclosporine (CyA). We analyzed elective biopsies obtained during first 3 months after heart transplantation in four patients treated with RAPA (24 biopsies) and seven patients receiving CyA (49 biopsies). Additional medications in both groups consisted of mycophenolate mofetil or azathioprine and prednisone. The intensity of rejection was assessed using the ISHLT scale; it was comparable in both groups based upon the number of results showing significant rejection and the average biopsy scores. Each slide was also examined under high-power magnification to sarcoplasmic and nuclear changes. Sarcoplasmic vacuolation, premyocytolysis and myocytolysis, nuclear staining, stromal fibrosis and edema, presence of vasculopathy, and lymphocytes infiltrating the myocardium occurred more frequently in the CyA group. The difference in the degree of hyperchromasia of the nuclei was highly significant (67% versus 10%, P <.00001). Our findings suggest that despite comparable levels of rejection as assessed using the ISHLT scale, patients treated with RAPA display fewer signs of cardiomyocytic alterations early after heart transplantation.
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Ciclosporina/uso terapéutico , Trasplante de Corazón/inmunología , Trasplante de Corazón/patología , Células Musculares/patología , Miocardio/patología , Sirolimus/uso terapéutico , Biopsia , Núcleo Celular/patología , Humanos , Inmunosupresores/uso terapéutico , Linfocitos/patología , Retículo Sarcoplasmático/patología , Vacuolas/patologíaRESUMEN
A retrospective analysis of all cases when cyclosporine (CyA) was replaced with sirolimus (SIR) to avoid the renal toxicity of CyA late after heart transplant (OHT) was discontinued due to advanced renal impairment in all five heart transplant recipients (four men, 1 women; age 41 years, range 38-45; time after OHT 5 years, range 4-14). The serum creatinine level at the time of SIR introduction, which was 298 micromol/L (range 217-676), had remained stable for the 6 months prior to conversion. Target SIR trough levels were 12-20 ng/mL. In four patients the last dose of CyA was immediately followed by the first dose of SIR, whereas in one patient CyA was tapered gradually in the presence of low-dose SIR. Deterioration of renal function with signs of fluid overload and increased serum creatinine levels (Delta: 77, 33-150 micromol/L) was observed in all patients. Two patients required dialysis during SIR treatment including one case of pulmonary edema requiring emergency hemodialysis. None of four biopsies showed significant rejection. Four patients were converted back to low-dose CyA (including the two patients requiring dialysis during SIR therapy); one was maintained on mycophenolate mofetil. The creatinine level at the time of SIR discontinuation was (range 250-753) micromol/L, 448. Eventually, all patients required dialysis. In conclusion, replacement of cyclosporine with sirolimus in heart transplant recipients with severe renal impairment late after transplantation may accelerate renal failure.
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Ciclosporina/uso terapéutico , Trasplante de Corazón/inmunología , Pruebas de Función Renal , Riñón/patología , Sirolimus/efectos adversos , Adulto , Creatinina/sangre , Ciclosporina/farmacocinética , Femenino , Humanos , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Riñón/efectos de los fármacos , Masculino , Persona de Mediana Edad , Diálisis Renal , Estudios RetrospectivosRESUMEN
The increased presence of intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1) in the myocardium after orthotropic heart transplantation (OHT) has been implicated in early and late organ rejection. The aim of this study was to investigate the changes in ICAM-1 and VCAM-1 during the first years post-OHT. Accordingly, we studied multiple endomyocardial biopsy specimens collected from 11 randomly selected patients (all males, mean age 46 +/- 11 years). Qualification criteria for OHT included: ischemic cardiomyopathy in 6 pts (55%) and idiopathic dilated cardiomyopathy in 5 pts (45%). All patients were receiving triple immunosuppressive regimen. The therapy consisted of cyclosporine, azathioprine, and prednisolone. Multiple endomyocardial biopsy specimens were collected at 7, 30, 90 and 360 days post OHT from all patients (pts), and examined routinely for histologic signs of organ rejection. To assess levels of adhesion molecules we used monoclonal antibodies (murine anti-human ICAM-1 and VCAM-1) on frozen sections. Immunoreactivity (IR) was detected using a commercially available kit. Intensity of IR was assessed based on a semiquantitative scoring system. In this study, IR scores > or = 2 + were considered positive for ICAM-1, and scores > or = 1 + were considered positive for VCAM-1. IR scores in specimens obtained from consecutive biopsies were compared with the initial biopsy collected at the day 7. The results were analyzed using nonparametric statistics. The routine evaluation revealed histological signs of organ rejection (> or = 2) in 2 pts at 7 days, in 5 pts at 30 days, in 3 pts at 90 days, and in 1 patient at 360 days. On the other hand, ICAM-1 and VCAM-1 expression were absent in the majority of patients at 7, 30 and 90 days, but their presence was significantly increased at 360 days (p < 0.05). Absence of the early expression of ICAM-1 and VCAM-1 may be related to the protective effect of triple immunosuppressive therapy in these patients. The expression of ICAM-1 and VCAM-1 strongly emerging at 1 year post OHT may reflect chronic rejection in myocardium. In conclusion, the immunohistological monitoring of the adhesion molecules in biopsy specimens during routine biopsy schedule may be helpful for the discovery of chronic rejection.
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Moléculas de Adhesión Celular/análisis , Trasplante de Corazón/patología , Miocardio/patología , Adulto , Biopsia , Endotelio Vascular/química , Endotelio Vascular/patología , Rechazo de Injerto/prevención & control , Humanos , Molécula 1 de Adhesión Intercelular/análisis , Masculino , Persona de Mediana Edad , Miocardio/química , Distribución Aleatoria , Factores de Tiempo , Molécula 1 de Adhesión Celular Vascular/análisisRESUMEN
The authors assessed morphometrically the parameters describing nuclei of the normal epithelium (superficial and basal layers), precancerous lesions (dysplasia and keratosis) and laryngeal cancer in the postoperative samples of 12 patients treated in the II Laryngology Clinic Silesian Medical Academy in Zabrze. Then the relationship between the integrated grade of grey (the index of changes in DNA structure) and the others kariometric parameters was evaluated. The value of the integrated grade of grey was the smallest in the superficial layers nuclei and the biggest in the laryngeal cancer one. The evaluation of the relationship was made by using the Spearman Rang Test. The integrated grade of grey was correlated with others quantitative nuclear measurements, though the correlation power was differ in the individual morphometrical stages.
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Neoplasias Laríngeas/genética , Neoplasias Laríngeas/patología , Lesiones Precancerosas/genética , Lesiones Precancerosas/patología , Adulto , Anciano , Femenino , Humanos , Cariometría/métodos , Queratosis/genética , Queratosis/patología , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de NeoplasiasRESUMEN
The authors assessed morphometrically nuclei of the normal mucosa, precancerous lesions and laryngeal cancer in the postoperative samples of 12 patients treated in the II Laryngology Clinic, Silesian Medical Academy in Zabrze. The results indicate significant cariometric differences of the normal mucosa, precancerous mucosal lesions and cancer of the larynx.
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Carcinoma de Células Escamosas/patología , Neoplasias Laríngeas/patología , Lesiones Precancerosas/diagnóstico , Adulto , Anciano , Femenino , Humanos , Mucosa Laríngea/patología , Masculino , Persona de Mediana Edad , Estadísticas no ParamétricasRESUMEN
The aim of the study was to relationship analysis between the karyometrical parameters of the laryngeal mucosa and the morphometrical states as well as the morphometrical comparison among the normal epithelium, precancerous lesions and cancer of the larynx. The following nuclear parameters were assessed: area, equivalent diameter, length, width, perimeter, convex area and perimeter, roundness, elongation and fulfillment. The relationship between karyometrical parameters and morphometrical lesions were found to be statistically significant. In some cases of the measurements there was no significant difference between the mild dysplasia cells and the superficial layers of the normal epithelium.
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Carcinoma de Células Escamosas/patología , Núcleo Celular/patología , Neoplasias Laríngeas/patología , Lesiones Precancerosas/patología , Adulto , Anciano , Epitelio/patología , Femenino , Humanos , Cariometría/métodos , Mucosa Laríngea/patología , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Endomyocardial biopsy to evaluate rejection in the transplanted heart is accepted at the "gold standard." The complexity of microscopic images suggested using digital methods for precise evaluating of acute rejection episodes with numerical representation. The aim of the present was study to characterize digitally acute rejection of the transplanted heart using complexity/fractal image analysis. MATERIAL AND METHODS: Biopsy samples harvested form 40 adult recipients after orthotropic heart transplantation were collected and rejection grade was evaluated according to the International Society for Heart and Lung Transplantation (0, 1a, 1b, or 3a) at transverse and longitudinal sections. Fifteen representative digital microscope images from each grade were collected and analyzed after Sobel edge detection and binarization. RESULTS: Only mean fractal dimension showed a progressive and significant increase and correlation based on rejection grade using longitudinal sections. Lacunarity and number of foreground pixels showed unequivocal results. CONCLUSION: Mean fractal diameter could serve as auxiliary digital parameter for grading of acute rejection in the transplanted heart.
Asunto(s)
Rechazo de Injerto/patología , Trasplante de Corazón , Miocardio/patología , Enfermedad Aguda , Adulto , Fractales , Humanos , Procesamiento de Imagen Asistido por ComputadorRESUMEN
BACKGROUND: A pilot study of orthotopic heart transplant (OHT) recipients showed that advanced glycation end-product (AGE) deposits were related to acute rejection episodes among subjects with diabetes mellitus (DM); in contrast, among non-DM patients it was associated with prolonged freedom from coronary artery vasculopathy (CAV). However the number of observations in non-diabetic subjects was low. The aim of the current study was to establish the role of AGEs in late endomyocardial biopsies (EMBs) among a larger group of non-diabetic patients. MATERIAL AND METHODS: Elective EMBs were performed at 3 years post OHT in 62 subjects with DM, namely, 57 males and 5 females of overall mean age of 50±8 years versus 92 free of DM, including 79 males and 13 females of mean age 51±13 years. We localized AGEs in myocardial paraffin sections using monoclonal mouse anti-AGE antibodies. The presence of AGEs in cardiomyocytes, stromal cells, capillaries, and arterioles was described with a semiquantitative scale. RESULTS: All-cause deaths, CAV, and CAV-related events were observed in 28% versus 23%, 27% versus 29%, and 15% versus 19% of non-DM versus DM patients (P=NS). The occurrence of AGEs was significantly more frequent among non-DM than DM subjects: cardiocytes, 100% versus 69% (P<.0001); stroma, 54% versus 31% (P=.0037); capillaries, 67% versus 31% (P<.0001); and arterioles, 26% versus 3% (P=.0002; chi-square). Among the DM group, mean EMB score correlated with AGE presence in cardiomyocytes (n=0.29; P<.05, Spearman test) AGE presence had no impact on survival or CAV development. CONCLUSION: AGE presence was more common in late EMB from non-diabetic than diabetic OHT recipients; they had no impact on survival or CAV in non-diabetic patients.
Asunto(s)
Productos Finales de Glicación Avanzada/metabolismo , Trasplante de Corazón/patología , Trasplante de Corazón/fisiología , Miocardio/metabolismo , Miocardio/patología , Adulto , Biopsia , Enfermedad de la Arteria Coronaria/metabolismo , Enfermedad de la Arteria Coronaria/patología , Complicaciones de la Diabetes/metabolismo , Complicaciones de la Diabetes/patología , Femenino , Rechazo de Injerto/metabolismo , Rechazo de Injerto/patología , Humanos , Masculino , Persona de Mediana Edad , Factores de TiempoRESUMEN
INTRODUCTION: The aim of this study was to assess peripheral blood lymphocyte subtypes (CD3+, CD19+, CD16+CD56+, CD4+, CD8+, and CD3+HLA-DR+) obtained from thoracic organ recipients at various periods after transplantation. MATERIAL AND METHODS: Seventeen patients after lung transplantation (LT) and 5 patients after heart transplantation (HT) included 13 males (76.5%) and 4 females (23.5%) of overall mean age at the time of transplantation of 46.7±11.55 years and mean body mass index of 21.1±4. Lymphocyte phenotypes were estimated using Simultest IMK Plus. RESULTS: A significant decrease in lymphocytes of the majority of subtypes was observed at 1 year posttransplantation compared with normal ranges: CD19+ B lymphocytes in 56% of patients, CD8+ T cells among 48% and CD16+CD56+ natural killer elements, 56%. In contrast, there were increased numbers of activated lymphocytes (CD3+HLA-DR+). Beyond the 1-year observation, we observed a trend to normalize parameters among the majority of subjects. CONCLUSION: A clear tendency to a decrease number of peripheral blood lymphocytes of various subtypes was observed among thoracic organ recipients in the first year posttransplantation with the exception of activated HLA-DR+ cells. After the first year, there was slow restoration of lymphocytes.