Presence of Candida spp. in the oral cavity of heart transplantation patients

Candida spp. can lead to infections or even fungal sepsis particularly among immunocompromized individuals. OBJECTIVE: The aim of the present study was to analyze the presence of Candida spp. among patients subjected to orthotopic heart transplantation. MATERIAL AND METHODS: Oral rinses from 50 patients subjected to orthotopic heart transplantation, aged 13 to 70 years, 40 males and 10 females, were examined. Sex-age-oral conditions matched-control included 50 individuals who were not subjected to any kind of transplantation and were not immunocompromized for any other reason. Counts of yeasts were expressed as median values of logarithm of cfu/mL and were statistically compared by Mann-Whitney's test. The heart transplant and control groups were compared for the presence of Candida spp. by chi-square test (p<0.05). RESULTS: The results showed statistically significant difference (p=0.001) in the prevalence of Candida spp. between the transplantation and control groups. Counts of yeasts (cfu/mL) in the transplanted group were significantly higher than in the control group (p=0.005). Candida albicans was the most prevalent species isolated from both groups. CONCLUSIONS: It was concluded that Candida yeast counts were higher in the heart transplant recipients than in the controls. There was higher variation of Candida species among the heart transplant patients and the most frequently isolated samples were: Candida albicans, Candida glabrata and Candida tropicalis. Isolates of Candida dubliniensis was not found in either of the groups.

Atrofia vellositaria duodenal inducida por micofenolato mofetil: caso clínico / Duodenal villous atrophy associated with Mycophenolate mofetil: report of one case

Mycophenolate mofetil (MMF) is an immunosupressor agent frequently used in patients after bone marrow or solid organ transplants. The most common adverse reactions of the drug are gastrointestinal, specially diarrhea and vomiting. We report a 53-year-old male, that received a heart transplant receiving immunosuppression with cyclosporine, mycophenolate mofetil and prednisone. Six months after the transplant, the patient started with diarrhea, anorexia and weight loss. A duodenal biopsy showed villous atrophy. Celiac disease and the presence of parasites were discarded. Mycophenolate mofetil was discontinued and one week later, diarrhea subsided. Two months later the patient was asymptomatic and recovered weight. A new duodenal biopsy showed absence of villous atrophy.

Pneumonia por Influenza A(H1N1) em paciente imunossuprimido após transplante cardíaco / Influenza A (H1N1) pneumonia in an immunossupressed patient after heart transplantation / Neumonía por Influenza A (H1N1) en paciente inmunosuprimido tras transplante cardiaco

O papel da resposta imunológica durante a infecção pelo vírus Influenza H1N1 não está totalmente estabelecido, mas acredita-se que atue de forma decisiva no agravamento do quadro e no aparecimento da síndrome de desconforto respiratório agudo. O papel de terapias imunomoduladoras no controle de infecções virais também não é consensual e faltam dados de literatura para se definir as indicações de seu uso. Neste relato de caso, apresentamos, segundo nosso conhecimento, pela primeira vez, o relato de um paciente transplantado cardíaco que apresentou infecção pelo vírus H1N1 e evoluiu de forma favorável, trazendo um questionamento sobre o real papel da terapia imunossupressora como fator de risco para a forma grave da doença.

The role of the immune response during Influenza H1N1 virus infection is not yet fully established, but it is believed that it decisively participates in the severity of the disease as well as in the development of acute respiratory distress syndrome. The role of immunomodulating therapies in the control of viral infections is not a consensus either, and data from the literature defining the indications for their use are lacking. The present report is, to our knowledge, the first on a heart transplant patient who developed H1N1 virus infection and had a favorable outcome, thus generating discussion on the real role of immunosuppressive therapy as a risk factor for the severe form of the disease.

El rol de la respuesta inmunológica durante la infección por el virus Influenza H1N1 no está totalmente establecido, sino que se cree que él actúe de forma decisiva en el agravamiento del cuadro y en el surgimiento del síndrome de distrés respiratorio agudo. El papel de terapias inmunomoduladoras en el control de infecciones virales también no es consensual y nos faltan datos de la literatura para definirse las indicaciones de su utilización. En este caso clínico presentamos, según nuestro conocimiento, por primera vez, el relato de un paciente transplantado cardiaco que presentó infección por el virus H1N1 y evolucionó de forma favorable, y aprovechamos para poner en cuestión el real papel de la terapia inmunosupresora como factor de riesgo para la forma severa de la enfermedad.

4-1BB (CD137) signals depend upon CD28 signals in alloimmune responses

Our previous study has demonstrated that there is a significant delay of Balb/c cardiac allograft rejection in the C57BL/6 4-1BB-deficient knockout recipient. In this study, we examined the effect of combined blockade of the 4-1BB and CD28 costimulatory pathways on cardiac allograft rejection in the C57BL/6-->Balb/c model. A long-term cardiac allograft survival was induced in CD28/4-1BB- deficient mice (>100 days survival in 3 of 4 mice), which was comparable with CD28-deficient mice (>100 days survival in 2 of 5 mice; P<0.2026). There was no long-term cardiac allograft survival in either wild-type (WT) or 4-1BB-deficient mice, even though 4-1BB-deficient recipients showed a significant delay of cardiac allograft rejection than WT mice. An in vitro mixed leukocyte reaction (MLR) assay showed that 4-1BB-deficient and WT mouse T cells had a similar responsiveness to allostimulation, whereas CD28- and CD28/4-1BB-deficient mouse T cells had a defective responsiveness to allostimulation. Furthermore, 4-1BB-deficient mice showed a similar CTL but an elevated Ab response against alloantigens as compared to WT mice, and the alloimmune responses of 4-1BB-deficient mice were abrogated in the CD28-deficient background. Overall, these results indicate that the CD28 costimulatory pathway plays a major role in the alloimmune response and that 4-1BB signals are dependent upon CD28 signals.

Complicaciones crónicas del trasplante cardiaco: Implicaciones clínicas y estrategias futuras / Chronic complications in cardiac transplantation: Clinical implications and future strategies

Chronic complications are situations which limit the long-term utility of cardiac transplantation. The allograft vasculopathy is the most important cause of death at 5 years alter transplantation. Another conditions are systemic arterial hypertension, nephropathies, diabetes mellitus, dyslipidemies and malignant neoplasies. The present manuscript summarizes the characteristics, clinical presentation and therapeutic strategies for this conditions.

Las complicaciones crónicas asociadas al trasplante cardiaco son situaciones que limitan la utilidad a largo plazo de este procedimiento. Dentro de ellas destaca la vasculopatía del injerto que constituye la primera causa de muerte a cinco años del trasplante. Otras situaciones incluyen la hipertensión arterial sistémica, la enfermedad renal, la diabetes mellitus de novo, las dislipidemias y las neoplasias. En el presente trabajo se resumen algunas de las características, causas, presentación clínica y estrategias de manejo de estas situaciones.

Comparaçäo farmacocinética entre apresentaçöes de ciclosporina A microemulsäo em transplantados cardíacos / Pharmacokinetic comparacion between cyclosporine A microemulsion formulations in heart transplant patients

O presente trabalho tem como finalidade analisar os princípios da equivalência terapêutica e da conversibilidade de dois preparados farmacêuticos com ciclosporina emulsäo: o produto referência e a ciclosporina microemulsäo genérica. Estudo multicêntrico, randomizado, com 25 transplantados cardíacos com evoluçäo maior de um ano e com terapia imunossupressora estável. O protocolo escolhido foi o X latino. Segundo este protocolo, cada paciente é seu próprio controle, e, durante a execuçäo da pesquisa, realiza-se o cruzamento da medicaçäo testada. Após assinatura de consentimento informado e avaliaçäo clínico-laboratorial inicial, os pacientes säo randomizados para iniciar com ciclosporina padräo ou com ciclosporina genérica. A cada 15 dias, os pacientes realizam novos contrtoles clínico e laboratorial e trocam de medicamentos. No total, säo dois períodos de observaçäo com duas rodadas de troca em cada. Os parâmetros farmacocinéticos dos dois produtos, a ciclosporinemia e a área sob a curva näo mostraram diferenças estatísticamente significativas. O efeito clínico e os efeitos colaterais foram semelhantes no período de observaçäo. Os resultados confirmam a total conversibilidade entre a ciclosporina microemulsäo padräo e a genérica.(au)

Trasplante de corazon / Heart transplantation

Se presenta la experiencia de 132 transplantes realizados en 129 pacientes durante un período de 15 años, desde 1985 hasta 1999, en un centro especializado en cirugía cardiovascular. El promedio de la edad para el grupo fue de 44.5 (11.8) años, con una proporción de hombres del 81 por ciento. 50.8 por ciento dé los pacientes estaban en clase funcional ni o IV de la clasificación de NYHA. Cuando se compararon los factores de riesgo preoperatorios e intraoperatorios con las complicaciones postoperatorias, se encontró que la antícoagulación previa, el tiempo de perfusión prolongado (mayor de 180 minutos) y la hipertensión pulmonar, eran factores de riesgo para complicaciones postoperatorias incluyendo la muerte, teniendo valores de p =0.000. Cuando se analizaron las complicaciones postoperatorias, se encontró que el tiempo prolongado de ventilación y de soporte farmacológico tenía una alta correlación estadística con valores de p=0.000. El análisis de las curvas de supervivencia actuarial nos permite demostrar que la supervivencia a 15 años es del 55.1 por ciento, siendo semejante a lo reportado por la Sociedad Internacional de Trasplante de Corazón y Pulmón

Expression of CD40 ligand, interferon-gamma and Fas ligand genes in endomyocardial biopsies of human cardiac allografts: correlation with acute rejection

The purpose of the present study was to investigate the expression (mRNA) of CD40 ligand (CD40L), interferon-gamma (IFN-gamma) and Fas ligand (FasL) genes in human cardiac allografts in relation to the occurrence of acute cardiac allograft rejection as well as its possible value in predicting acute rejection. The mRNA levels were determined by a semiquantitative reverse transcriptase-polymerase chain reaction method in 39 samples of endomyocardial biopsies obtained from 10 adult cardiac transplant recipients within the first six months after transplantation. Biopsies with ongoing acute rejection showed significantly higher CD40L, IFN-gamma and FasL mRNA expression than biopsies without rejection. The median values of mRNA expression in biopsies with and without rejection were 0.116 and zero for CD40L (P<0.003), 0.080 and zero for IFN-gamma (P<0.0009), and 0.156 and zero for FasL (P<0.002), respectively. In addition, the levels of IFN-gamma mRNA were significantly increased 7 to 15 days before the appearance of histological evidence of rejection (median of 0.086 in pre-rejection biopsies), i.e., they presented a predictive value. This study provides further evidence of heightened expression of immune activation genes during rejection and shows that some of these markers may present predictive value for the occurrence of acute rejection.

Biopsia endomiocardica: patron de oro para el diagnostico del rechazo agudo en el trasplante cardiaco / Endomyocardial biopsy

El trasplante cardíaco es la alternativa terapéutica para la falla cardíaca refractaria al tratamiento farmacológico. El manejo de los inmunosupresores y el seguimiento de los pacientes trasplantados se basa en la biopsia endomiocárdica, la cual constituye el patrón de oro para el diagnóstico del rechazo agudo. Permite la valoración de los resultados del tratamiento, así como el diagnóstico de isquemia, infecciones oportunistas y neoplasias post-trasplante. En el rechazo crónico, la biopsia detecta estadios avanzados con lesiones isquémicas y compromiso de las arterias coronarias intramiocárdicas

Analise dos fatores de risco da doença vascular do enxerto em pacientes assintomáticos após transplante cardíaco / Analysis of the risk factors for allograft vasculopathy in asymptomatic patients after cardiac transplantation

OBJECTIVE: To study the influence of immune and nonimmune risk factors on the development of allograft vasculopathy after cardiac transplantation. METHODS: We studied 39 patients with a mean age of 46 + or - 12 years. The following variables were analyzed: weight (kg), body mass index (kg/m²), donor's age and sex, rejection episodes in the first and second years after transplantation, systolic and diastolic blood pressures (mmHg), total cholesterol and fractions (mg/dL), triglycerides (mg/dL), diabetes, and cytomegalovirus infection. The presence of allograft vasculopathy was established through coronary angiography. RESULTS: Allograft vasculopathy was observed in 15 (38 percent) patients. No statistically significant difference was observed between the two groups in regard to hypertension, cytomegalovirus infection, diabetes, donor's sex and age, rejection episodes in the first and second years after transplantation, and cholesterol levels. We observed a tendency toward higher levels of triglycerides in the group with disease. Univariate and multivariate analyses showed statistically significant differences between the two groups when we analyzed the body mass index (24.53 + or - 4.3 versus 28.11 + or - 4.6; p=0.019). CONCLUSION: Body mass index was an important marker of allograft vasculopathy in the population studied

Tratamento ambulatorial de rejeiçäo persistente com methotrexate em pacientes submetidos a transplante cardíaco estáveis clinicamente / Treatment of persistent rejection with methotrexate in stable patients submmitted to heart transplantation

OBJECTIVE:To evaluate the use of methotrexate for the treatment of recurrent rejection in heart transplant recipients. METHODS: We studied 6 patients submitted to heart transplantation that showed rejection grade ü 3A (ISHLT) in two consecutives endomyocardial biopsy specimens. The dose was 11.26ñ3.75mg/week. The evaluated data were: ventricular function, endomyocardial biopsy, white cell count and number of rejection episodes before and after methotrexate administration. RESULTS: There was a reduction in the number of rejection episodes (5.17ñ1.47 before methotrexate; 2.33ñ1.75 after 6 months and 3.17ñ2.99 after 12 months of treatment, p=0.0193). The ventricular function was normal with ejection fraction of 76.5ñ4.80 before and 75.6ñ4.59 after methotrexate (p=0.4859). One patient did not finish the treatment because he showed signs of rejection associated with severe pericardial effusion. Five patients had a reduction in the white cell count (8,108ñ23.72 before and 5650ñ1350 after methotrexate, p=0.0961). One pulmonary infection with complete resolution after antibiotic treatment was observed. CONCLUSION: Methotrexate in low doses is an effective adjunct therapy in the treatment of recurrent rejection after heart transplantation.

Consideraciones y experiencia con el trasplante cardíaco: Clínica Cardiovascular Santa María de Medellín / Considerations and experiences with cardiac transplantation: Clínica Cardiovascular Santa María de Medellín

Han transcurrido 32 años desde que se practicó el primer trasplante cardiaco exitoso en el hombre, y 20 desde que, gracias a los conocimientos acumulados con relacion al tratamiento del paciente, al control del rechazo y la infeccion y al advenimiento de la ciclosporina, el procedimiento paso de la fase experimental a la de aplicacion clinica. Las indicaciones están bien definidas y hacen relacion, con raras excepciones, a un estado de insuficiencia cardiaca irreversible e intratable; asi mismo, están claras las contraindicaciones y criterios de exclusion. Sinembargo, representa solo una de las facetas de la terapeutica quirurgica que puede ser ofrecida por centros dedicados al trasplante de los pacientes con insuficiencia cardiaca. La cirugia para la isquemia reversible, distorsion de la geometria ventricular y enfermedad valvular, es hoy en dia exitosa en algunos pacientes a pesar de tener una funcion ventricular pobre y sintomas de insuficiencia cardiaca. La estadistica muestra una supervivencia buena a largo plazo y sobre todo una mejoria sustancial en la calidad de vida. Esto lo hemos podido comprobar con nuestra casuistica de 131 pacientes trasplantados cuya experiencia presentamos aqui, que nos ha llevado a poder ofrecer este recurso a nuestros pacientes.

Effect of angiopeptin and aspirin on accelerated graft atherosclerosis in transplanted mouse heart

In this study of the inhibitory effects of angiopeptin and aspirin on the development of accelerated graft atherosclerosis (AGAS), 22 B10.BR mice received intra-abdominal heterotopic heart transplants from B10.A mice, without immunosuppression. Group 1 (n = 5) received no pharmacological intervention, Group 2 (n = 6) was treated with angiopeptin, Group 3 (n = 5) with aspirin, and Group 4 (n = 6) with both. There was no significant difference in the incidence of AGAS among these groups. The magnitude of intimal lesion development showed less narrowing of large vessels (> 100 microns in diameter) in groups 2 and 4--i.e. the groups received angiopeptin (Group 1 = 46.9 +/- 9.3%, Group 2 = 28.5 +/- 9.2%, Group 3 = 44.1 +/- 10.9%, Group 4 = 24.2 +/- 5.9%; p < 0.01). Comparison of the fraction of tropomyosin-positive staining cells in the intima revealed a lesser degree of staining in Group 2 (p < 0.01). No intervention was effective in preventing smooth muscle cell proliferation in the media or inflammatory cell infiltration in the adventitia. In conclusion, our data suggest that angiopeptin is effective in the direct inhibition of intimal smooth muscle cell proliferation in relatively large vessels, whereas aspirin exhibits no inhibitory role in the progression of AGAS. Angiopeptin appears to be a potential therapeutic agent for inhibiting the progression of postoperative AGAS in clinical heart transplantation.

Perspectivas del xenotrasplante cardíaco / The future of heart xenotransplants

El desarrollo actual de la biología molecular y de la ingeniería genética permiten vislumbrar la posibilidad de fabricar xenoinjertos compatibles con características moleculares semejantes a las humanas. Un enfoque para la construcción de un xenoinjerto cardíaco a partir de una especie filogenéticamente distanciada (cerdo) consiste en reducir la densidad del epítope alfa-galactosil de la superficie celular por medio de la transferencia y sobre expresión en el cerdo del gen de la fucosiltransferasa humana, lo que permitiría al animal producir un epítope semejante al antígeno H humano. El volumen de conocimientos acumulado hasta el momento permite plantear bases teóricas claras para la fabricación de xenoinjertos compatibles

Caracterizacao de cepas do Trypanosoma cruzi isoladas de doencas nos quais foi realizado transplante de coracao / Caracterization of Trypanosoma cruzi strains isolated from patients with heart transplantation

Tres cepas do Trypanosoma cruzi foram isoladas de pacientes com doenca de Chagas cronica, receptores de coracao por meio de transplante. Houve a caracterizacao dela atraves de modelo experimental baseado no emprego de camundongos, com avaliacao de parasitismo, mortalidade e intensidade da inflamacao no coracao, alem de analise do grau de parasitismo nesse orgao. Como controle, teve lugar comparacao com o comportamento da ja bem conhecida cepa Y. Ficaram caracterizadas atuacoes diferentes das cepas, ao serem valorizados os parametros citados, sem correlacao rigorosa com as evolucoes pos-transplantes, que sofrem a influencia de varios fatores, entre os quais podem estar particularidades vinculadas ao parasitismo.