Non-invasive messenger RNA transcriptional evaluation in human kidney allograft dysfunction

The aim of the present study was to evaluate messenger RNA expression in kidney allograft recipients. Forty-four kidney transplant recipients were evaluated up to three months after grafting. After transplantation, peripheral blood samples were drawn sequentially for real-time polymerase chain reaction analyses of perforin and TIM-3 genes. Biopsies were obtained to evaluate acute graft dysfunction and interpreted according to the Banff classification. Eight patients presented episodes of acute rejection. Recipients with rejection had significantly higher levels of TIM-3 mRNA transcripts compared to those without rejection (median gene expression 191.2 and 36.9 mRNA relative units, respectively; P<0.0001). Also, perforin gene expression was higher in patients with rejection (median gene expression 362.0 and 52.8 mRNA relative units; P<0.001). Receiver operating characteristic curves showed that the area under the curve (AUC) for the TIM-3 gene was 0.749 (95%CI: 0.670-0.827). Perforin gene mRNA expression provided an AUC of 0.699 (95%CI: 0.599 to 0.799). Overall accuracy of gene expression was 67.9% for the TIM-3 gene and 63.6% for the perforin gene. Combined accuracy was 76.8%. Negative predictive values were 95.3% for the TIM-3 gene, 95.5% for the perforin gene, and 95.4% in the combined analyses. Gene expression was significantly modulated by rejection treatment decreasing 64.1% (TIM-3) and 90.9% (perforin) compared to the median of pre-rejection samples. In conclusion, the longitudinal approach showed that gene profiling evaluation might be useful in ruling out the diagnosis of acute rejection and perhaps evaluating the efficacy of treatment.

Upregulation of microRNA 142-3p in the peripheral blood and urinary cells of kidney transplant recipients with post-transplant graft dysfunction

We analyzed microRNA (miR)-142-3p expression in leucocytes of the peripheral blood and urinary sediment cell samples obtained from kidney transplant recipients who developed graft dysfunction. Forty-one kidney transplant recipients with kidney graft dysfunction and 8 stable patients were included in the study. The groups were divided according to histological analysis into acute rejection group (n=23), acute tubular necrosis group (n=18) and stable patients group used as a control for gene expression (n=8). Percutaneous biopsies were performed and peripheral blood samples and urine samples were obtained. miR-142-3p was analyzed by real-time polymerase chain reaction. The group of patients with acute tubular necrosis presented significantly higher expressions in peripheral blood (P<0.05) and urine (P<0.001) compared to the stable patients group. Also, in the peripheral blood, miR-142-3p expression was significantly higher in the acute tubular necrosis group compared to the acute rejection group (P<0.05). Urine samples of the acute rejection group presented higher expression compared to the stable patients group (P<0.001) but the difference between acute tubular necrosis and acute rejection groups was not significant in the urinary analyzes (P=0.079). miR-142-3p expression has a distinct pattern of expression in the setting of post-operative acute tubular necrosis after kidney transplantation and may potentially be used as a non-invasive biomarker for renal graft dysfunction.

Meaning of leprosy for people who have experienced treatment during the sulfonic and multidrug therapy periods / Significado da hanseníase para pessoas que viveram o tratamento no período sulfônico e da poliquimioterapia / Significado de la lepra para personas que experimentaron el tratamiento en el período sulfónico y de poliquimioterapia

AbstractObjective: to analyze the meanings of leprosy for people treated during the sulfonic and multidrug therapy periods.Method: qualitative nature study based on the Vigotski's historical-cultural approach, which guided the production and analysis of data. It included eight respondents who have had leprosy and were submitted to sulfonic and multidrug therapy treatments. The participants are also members of the Movement for Reintegration of People Affected by Leprosy.Results: the meanings were organized into three meaning cores: spots on the body: something is out of order; leprosy or hanseniasis? and leprosy from the inclusion in the Movement for Reintegration of People Affected by Leprosy.Conclusion: the meanings of leprosy for people submitted to both regimens point to a complex construction thereof, indicating differences and similarities in both treatments. Health professionals may contribute to the change of the meanings, since these are socially constructed and the changes are continuous.

ResumoObjetivo:analisar significados da hanseníase para as pessoas que foram tratadas no período sulfônico e no período da poliquimioterapia.Método:estudo de natureza qualitativa fundamentado na abordagem histórico-cultural de Vigotski, a qual orientou a construção e análise dos dados. Foram incluídos oito entrevistados que já tiveram hanseníase e que realizaram tratamento no período sulfônico e da poliquimioterapia, sendo participantes do Movimento de Reintegração das Pessoas Atingidas pela Hanseníase.Resultados:os significados foram organizados em três núcleos de significação: manchas no corpo: alguma coisa está fora de ordem; lepra ou hanseníase? e hanseníase a partir da inserção no Movimento de Reintegração das Pessoas Atingidas pela Hanseníase.Conclusão:os significados de hanseníase para pessoas tratadas nos dois períodos apontam para a construção complexa dos mesmos, indicando diferenças e semelhanças nos dois períodos. Os profissionais de saúde podem contribuir para a mudança de significados, pois esses são socialmente construídos e as transformações são contínuas.

ResumenObjetivo:analizar los significados de la lepra para las personas que fueron tratadas en el período sulfónico y en el período de poliquimioterapia.Método:estudio de naturaleza cualitativa fundamentado en el abordaje histórico cultural de Vygotsky, el cual orientó la construcción y análisis de los datos. Fueron incluidos ocho entrevistados que ya tuvieron lepra y que realizaron tratamiento en el período sulfónico y de poliquimioterapia, siendo participantes del Movimiento de Reintegración de Personas Afectadas por la Lepra.Resultados:los significados fueron organizados en tres núcleos de significación: manchas en el cuerpo: alguna cosa está fuera de orden; ¿Lepra o enfermedad de Hansen?; y lepra a partir de la inserción en el Movimiento de Reintegración de Personas Afectadas por la Lepra. Conclusión: los significados de la lepra para las personas tratadas en los dos períodos apuntan para la construcción compleja de los mismos, indicando diferencias y semejanzas en los dos períodos. Los profesionales de la salud pueden contribuir para el cambio de significados, ya que estos son socialmente construidos y las transformaciones son continuas.

Instrument to assess the nursing care product: development and content validation / Instrumento para avaliação do produto do cuidar em enfermagem: desenvolvimento e validação de conteúdo / Instrumento para evaluación del producto del cuidar en enfermería: desarrollo y validación de contenido

AbstractObjectives: develop and validate the content of a tool about nursing care production.Method: the data were collected between 2011 and 2013, based on focus groups, the application of semistructured questionnaires (prototype test) and the Delphi technique. The focus groups were used to produce the instrument items and held at three hospitals in the interior of the State of São Paulo, involving 20 nurses. A panel of 10 experts evaluated the instrument.Results: after two phases of the Delphi technique, the tool consisted of eight items. The content validity index of the scale corresponded to ≥0.9 and the content validity of the items ranged between 0.8 and 1.0, indicating the maintenance of the structure and content. The assertion on the applicability in daily nursing practice showed a content validity index of the scale equal to 0.8.Conclusion: this study permitted the development and content validation of scale on nursing care production, equipping the nurses in their management practice.

ResumoObjetivos:desenvolver e validar o conteúdo de um instrumento sobre produção do cuidado de enfermagem.Método:a coleta de dados ocorreu entre 2011 e 2013, a partir de grupos focais, aplicação de questionários semiestruturados (teste do protótipo) e técnica Delphi. Os grupos focais foram utilizados para geração de itens do instrumento e realizados em três hospitais do interior do Estado de São Paulo, com a participação de 20 enfermeiros. A apreciação do instrumento foi conduzida por um painel de 10 especialistas.Resultados:após duas fases da técnica Delphi, o instrumento passou a ser constituído por oito itens. O índice de validade do conteúdo da escala foi de ≥0,9 e a validade dos conteúdos dos itens apresentou variação de 0,8 a 1,0, indicando a manutenção da estrutura e do conteúdo. A afirmativa referente à aplicabilidade na prática diária do enfermeiro apresentou índice de validade do conteúdo da escala de 0,8.Conclusão:este estudo possibilitou desenvolver e validar o conteúdo de uma escala sobre produção do cuidado de enfermagem, instrumentalizando os enfermeiros em sua prática gerencial.

ResumenObjetivos:desarrollar y validar el contenido de un instrumento sobre producción del cuidado de enfermería.Método:los datos fueron recolectados entre 2011 y 2013, a partir de grupos focales, aplicación de cuestionarios semiestructurados (prueba del prototipo) y técnica Delphi. Los grupos focales fueron utilizados para generar ítems del instrumento y organizados en tres hospitales del interior del Estado de São Paulo, con la participación de 20 enfermeros. La apreciación del instrumento fue conducida por un panel de 10 especialistas.Resultados:tras dos fases de la técnica Delphi, el instrumento pasó a ser constituido por ocho ítems. El índice de validez de contenido de la escala fue ≥0,9 y la validez de los contenidos mostró variación de 0,8 a 1,0, indicando la manutención de la estructura y del contenido. La afirmativa respecto a la aplicabilidad en la práctica diaria del enfermero mostró índice de validez del contenido de la escala de 0,8.Conclusión:este estudio permitió desarrollar y validar el contenido de una escala sobre producción del cuidado de enfermería, instrumentalizando los enfermeros en su práctica gerencial.

Pediatric lung transplantation: 10 years of experience

Lung transplantation is a well-established treatment for advanced lung diseases. In children, the diseases that most commonly lead to the need for a transplantation are cystic fibrosis, pulmonary hypertension, and bronchiolitis. However, the number of pediatric lung transplantations being performed is low compared with the number of transplants performed in the adult age group. The objective of this study was to demonstrate our experience with pediatric lung transplants over a 10-year period in a program initially designed for adults.

Valor crítico da citrulina para as complicações do enxerto no transplante de intestino / Critical value of citrulline for complications of intestinal transplant graft

OBJETIVO: Analisar, numa ampla amostra, o valor crítico da citrulina que confirma a presença das principais complicações do enxerto: rejeição e infecção. MÉTODOS: Foram coletadas 2135 amostras de citrulina sérica, na forma de gota de sangue seca, de 57 doentes submetidos a transplante de intestino/multivisceral no Jackson Memorial Hospital na Universidade de Miami, de março de 2004 a abril de 2006. Todas as amostras são do pós-operatório três meses em diante, passada a conhecida curva de elevação da citrulina após a recuperação das lesões causadas pela isquemia e reperfusão do pós-transplante. RESULTADOS: Utilizando um valor limite menor que 13 µmoles/L, a sensibilidade da citrulina foi de 96,4 por cento para detectar rejeicão celular aguda (RCA) moderada ou grave. A especificidade para as complicações mais freqüentes, rejeição e infecção foi de 54 por cento-74 por cento nas crianças e 83 por cento-88 por cento nos adultos, e o valor preditivo negativo (VPN) foi > 99 por cento. CONCLUSÃO: A citrulina pode ser utilizada como método não-invasivo para avaliar a evolução do enxerto intestinal após três meses do TI. Os episódios de RCA moderado e grave podem ser afastados quando o valor da citrulina for maior que 13 µmoles/L devido ao alto valor preditivo negativo.

OBJECITIVE: A biochemical marker for detection of acute cellular rejection following small intestine transplantation has been sought. Citrulline, a non- protein amino acid synthesized mainly by functioning enterocytes, has been proposed. Trial sensitivity has been reportedly high but with low specificity. Thus, the goal was to determine, in a sufficiently large analysis, the significant value of citrulline level in the post-transplant setting, which would correlate with complications such as rejection and infection. METHODS: Since March, 2004 2,135 dried blood spot (DBS) citrulline samples were obtained from 57 small intestine transplant recipients three months or more after post-transplant, i.e., once the expected period of recovery in the citrulline levels had occurred. RESULTS: Using a <13 vs. > 13 µmoles/L cut off point, sensitivity of DBS citrulline for the detection of moderate or severe ACR was extremely high (96.4 percent). Furthermore, specificity estimates (given the absence of ACR and these particular infections), while controlling for time-to-DBS sample were reasonably high (54 percent-74 percent in children and 83 percent-88 percent in adults), and the negative predictive value (NPV) was >99 percent. CONCLUSION: Citrulline is a non-invasive marker to evaluate problems of the intestinal graft after three months post-transplant. Due to the high NPV, a moderate or severe ACR can be ruled out, based exclusively on knowledge of a high value for DBS citrulline.

Evidencia del impacto de los anticuerpos anti-HLA y anti-MICA en la pérdida del injerto renal / Evidence on the role of HLA and MICA antibodies in renal graft loss

Antecedentes: Los anticuerpos anti-HLA y anti-MICA se han asociado cada vez con mayor frecuencia a menor supervivencia del injerto renal. El objetivo de este estudio es comunicar la frecuencia de pérdida del injerto dos años después de la detección de anticuerpos anti-HLA, anti-MICA, o ambos, en un grupo de receptores de trasplante renal (RTR). Métodos: Estudiamos a 196 RTR con injerto funcional. El suero de los pacientes fue analizado para la presencia de anticuerpos IgG anti-HLA clase I y clase II con Luminex utilizando LABScreen®Mixed y LABScreen® PRA. La presencia de anticuerpos anti-MICA en el mismo suero se analizó por Luminex. Resultados: De 196 RTR (edad promedio 36.7 años, 42% sexo femenino), 124 (63.3%) fueron negativos a todos los anticuerpos estudiados y 72 (36.7%) fueron positivos: 34 para anticuerpos anti-HLA solo, 29 para anticuerpos anti-MICA solo y nueve para anticuerpos anti-HLA+anti-MICA. A una mediana de seguimiento de 20.5 meses (1.2-25.2), ocho pacientes perdieron el injerto por daño crónico del mismo, confirmado por biopsia: 2/124 (1.6%) del grupo de anticuerpos negativos y 6/72 (8.3%) del grupo de anticuerpos positivos, con una supervivencia del injerto significativamente inferior para el grupo de anticuerpos positivos (p=0.046, log-rank test). Conclusiones: La presencia de anticuerpos circulantes estuvo asociados con riesgo incrementado para pérdida del injerto; la coexistencia de anticuerpos anti-HLA y anti-MICA produjo el riesgo más alto para pérdida del injerto en la población analizada.

BACKGROUND: HLA and MICA antibodies are increasingly associated with poorer graft survival. The aim of this study is to report the frequency of graft loss 2 years after the detection of HLA abs and MICA abs among a group of kidney transplant recipients. METHODS: We tested 196 patients with a functioning graft. Sera were screened for HLA and MICA IgG abs by Luminex, using the LABScreen Mixed, and LABScreen PRA. The sera were screened for MICA abs by Luminex. RESULTS: Of 196 kidney transplant recipients (mean age 36.7 years, 42% female), one hundred twenty four (63.3%) were negative to all tested abs, and 72 (36.7%) were positive for: HLA abs alone = 34, MICA abs alone = 29, and HLA+MICA abs = 9. At a median followup of 20.5 (1.2-25.2) months, 8 patients lost their grafts due to biopsy-confirmed chronic allograft injury: 2/124 (1.6%) ab-negative, and 6/72 (8.3%) ab-positive, with a significantly lower survival for the Ab-positive group (p = 0.046, log-rank test). CONCLUSIONS: The presence of circulating abs was associated with an increased risk of graft loss, and the coexistence of HLA and MICA abs increases the risk of graft loss.

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.

Prolactina como inmunomodulador / Prolactin how immunomodulator

El propósito de la presente revisión es explorar el papel de la prolactina como inmunomodulador en la respuesta inmune. La prolactina tiene función trófica en la proliferación de los linfocitos. Las células del sistema inmunitario tienen receptores en su superficie para la prolactina, más aún, los linfocitos son capaces de sintetizar y secretar prolactina. Diferentes estados en el nivel de prolactina ejercen una respuesta diferente en el sistema inmunitario, la disminución en la prolactina provoca un deterioro en la respuesta inmunitaria, mientras que el aumento de la prolactina ejerce un incremento de la respuesta inmunitaria. Las alteraciones en la prolactina se han descrito en muchas enfermedades con fondo inmunológico, como el lupus eritematoso sistémico, el síndrome de Reiter, artritis por adyuvantes, uveítis, transplante de órganos. La acumulación de pruebas al momento actual del papel que juega la prolactina como inmunomodulador puede tener un profundo impacto clínico en las enfermedades autoinmunitarias pero aún están en camino de determinarse

Stored blood - an effective immunosuppressive method from unrelated donors: an 11-year follow-up

Thirty-seven patients were submitted to kidney trasnplantation after transfusion at 2-weeck intervals with 4-week stored blood from their potential donors. All patients and donors were typed for HLA-A-B and DR antigens. The patients were also tested for cytotoxic antibodies against donor antigens before each transfusion. The percentage of penel reactive antibodies (PRA) reative antibodies (PRA) was determined against a selected panel of 30 cell donors before and after the transfusions. The patients were immunosuppressed with azathioprine and prednisone. Rejection crises were treated with methylprednisolone. The control group consisted of 23 patients who received grafts from an unrelated donor but who did not receive donor-specific pretransplant blood transfusion. The incidence and reversibility of rejection episodes, allograft loss caused by rejection, and patient and graft survival rates were determined for both groups. Non-parametric methods (chi-square and Fisher tests) were used for statistical analysis, with the level of significance set at P<0.05. The incidence and reversibility of rejection crises during the first 60 post-transplant days did not differ significantly between groups. The actuarial graft and patient survival rates at five years were 56 percent and 77 percent, respectively, for the treated group and 39,8 percent and 57.5 percent for the control group. Graft loss due to rejection was significantly higher in the untreated group (P = 0.0026) which also required more intense immunosuppression (P = 0.0001). We conclude that tranfusions using stored blood have the immunosuppressive effect of fresh blood transfusions without the risk of provoking a widespread formation of antibodies. In addition, this method permits a reduction of the immunosuppressive drugs during the process with-out impairing the adequate funsctioning of the renal graft.

Post transplant diabetes mellitus in live related renal allograft recipients: a single centre experience.

The incidence of post-transplant diabetes mellitus (PTDM) was evaluated in 250 patients who underwent live-related renal transplantation at our hospital between 1978 and 1992. Twelve (4.8%) patients developed PTDM requiring drug therapy. PTDM occurred in 4 of 197 (2%) patients on conventional prednisolone-azathioprine immunosuppression as compared to 8 of 53 (15.1%) patients receiving cyclosporine in addition (triple-therapy). Three patients (25%) developed PTDM during or immediately following anti-rejection therapy with intravenous methylprednisolone. Eight patients (66.6%) developed PTDM within six months of transplantation. Majority of our patients (66.6%) could be managed successfully with oral hypoglycemic agents. Two patients (16.6%) showed spontaneous resolution of hyperglycemia within six months of onset of PTDM. Eleven patients (91.6%) were symptomatic for their hyperglycemia with two patients presenting as 'pseudorejection' and one with diabetic ketoacidosis. Females were more predisposed to develop PTDM in our study (10% vs. 4.1%). HLA-B15 and DR 3 were the commonest phenotypes in our PTDM patients. No other known predisposing or triggering factors associated with PTDM were found in our patients. The current study suggests, that addition of cyclosporine to the conventional immunosuppression in live-related renal allograft recipients has contributed to an increased incidence of post-transplant diabetes mellitus. Close and regular blood sugar monitoring is thus recommended in post-transplant patients especially those on triple drug immunosuppression.

Free radical injury in human renal allograft rejection.

Plasma and renal tissue levels of lipid peroxide and plasma vitamin E were estimated as measures of free radical injury in five renal allograft recipients with untreated and four with unsuccessfully treated acute cellular rejection and compared with 11 control patients with minimal change disease. Plasma lipid peroxide was significantly higher in patients studied before antirejection therapy (13.2 +/- 3.5 nmol/ml; P < 0.01) as well as in those after unsuccessful antirejection treatment (11.7 +/- 0.7 nmol/ml; P < 0.01), compared to controls (5.7 +/- 2.8 nmol/ml). Levels of plasma vitamin E and renal tissue lipid peroxide were similar in both groups, however the latter was significantly raised in patients evaluated prior to antirejection therapy than in those after unsuccessful antirejection therapy (5.1 +/- 1.7 and 3.0 +/- 0.8 nmol/mg protein; P < 0.05). These findings suggest possible free radical mediated injury during renal allograft rejection.