RESUMO
The Strategic Implementation Plan of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) proposed six Action Groups. After almost three years of activity, many achievements have been obtained through commitments or collaborative work of the Action Groups. However, they have often worked in silos and, consequently, synergies between Action Groups have been proposed to strengthen the triple win of the EIP on AHA. The paper presents the methodology and current status of the Task Force on EIP on AHA synergies. Synergies are in line with the Action Groups' new Renovated Action Plan (2016-2018) to ensure that their future objectives are coherent and fully connected. The outcomes and impact of synergies are using the Monitoring and Assessment Framework for the EIP on AHA (MAFEIP). Eight proposals for synergies have been approved by the Task Force: Five cross-cutting synergies which can be used for all current and future synergies as they consider overarching domains (appropriate polypharmacy, citizen empowerment, teaching and coaching on AHA, deployment of synergies to EU regions, Responsible Research and Innovation), and three cross-cutting synergies focussing on current Action Group activities (falls, frailty, integrated care and chronic respiratory diseases).
Assuntos
Envelhecimento , Comportamentos Relacionados com a Saúde , População Branca , Acidentes por Quedas/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Comportamento Cooperativo , Europa (Continente) , Idoso Fragilizado , Humanos , Múltiplas Afecções Crônicas , Inovação Organizacional , Polimedicação , Inquéritos e QuestionáriosRESUMO
The objective of Integrated Care Pathways for Airway Diseases (AIRWAYS-ICPs) is to launch a collaboration to develop multi-sectoral care pathways for chronic respiratory diseases in European countries and regions. AIRWAYS-ICPs has strategic relevance to the European Union Health Strategy and will add value to existing public health knowledge by: 1) proposing a common framework of care pathways for chronic respiratory diseases, which will facilitate comparability and trans-national initiatives; 2) informing cost-effective policy development, strengthening in particular those on smoking and environmental exposure; 3) aiding risk stratification in chronic disease patients, using a common strategy; 4) having a significant impact on the health of citizens in the short term (reduction of morbidity, improvement of education in children and of work in adults) and in the long-term (healthy ageing); 5) proposing a common simulation tool to assist physicians; and 6) ultimately reducing the healthcare burden (emergency visits, avoidable hospitalisations, disability and costs) while improving quality of life. In the longer term, the incidence of disease may be reduced by innovative prevention strategies. AIRWAYSICPs was initiated by Area 5 of the Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing. All stakeholders are involved (health and social care, patients, and policy makers).
Assuntos
Transtornos Respiratórios/terapia , Envelhecimento , Asma/terapia , Tomada de Decisões , Europa (Continente) , União Europeia , Guias como Assunto , Humanos , Cooperação Internacional , Área Carente de Assistência Médica , Doença Pulmonar Obstrutiva Crônica/terapia , Qualidade de Vida , Rinite/terapia , Fatores de Risco , Organização Mundial da SaúdeRESUMO
Soluble forms of some cell adhesion molecules (CAM), sICAM-1, sVCAM-1, and sE-selectin, are elevated in the sera and plasma of patients with inflammation, arthritis, diabetes, and cancer. Increased levels of these soluble molecules in patients with cancer have been shown to correlate with disease progression and survival. This suggests that increased expression of the soluble forms of CAMs may play an important role in cancer cell growth and metastasis and may be prognostic and/or predictive of malignant disease. In this retrospective study, we assessed the clinical significance of sICAM-1, sVCAM-1, and sE-selectin in 95 patients with metastatic breast cancer enrolled in clinical trials of high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT). The significance of soluble HER-2 (sHER-2) and sFAS status, determined in previous studies for this group of patients, was also included in this analysis. Univariate analysis showed that sICAM-1, sVCAM-1, sFas, sHER-2 positive status, and the presence of liver metastases were significant prognostic factors for both progression-free survival (PFS) and overall survival (OS) in the total patient group. In multivariable analysis, HER-2 and sFAS were shown to be independent prognostic factors for PFS and OS. Within the various treatment groups examined, sICAM-1 was a prognostic factor for clinical outcome for patients with metastatic breast cancer enrolled in trials with cyclophosphamide- and carboplatin-based or vinblastine-based HDC, but not in trials with paclitaxeland cyclophosphamide-based HDC.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama , Selectina E/sangue , Molécula 1 de Adesão Intercelular/sangue , Molécula 1 de Adesão de Célula Vascular/sangue , Adulto , Neoplasias da Mama/sangue , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Ensaios Clínicos Fase II como Assunto , Progressão da Doença , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Receptor ErbB-2/sangue , Estudos Retrospectivos , Transplante de Células-Tronco , Taxa de Sobrevida , Transplante Autólogo , Receptor fas/sangueRESUMO
Cryopreservation of stem cells after collection from peripheral blood or bone marrow for autologous transplantation necessitates protection with dimethyl sulfoxide (DMSO). Unfortunately, DMSO, when infused with the thawed cell suspension, may induce serious complications and side effects. To assess whether depletion of DMSO before autografting affects safety and efficacy, 56 consenting consecutive patients treated with high-dose chemotherapy and autologous blood stem cell transplantation were assigned to obtain either an untreated or DMSO-depleted autograft. On the day of transplantation, the cryopreserved cells were thawed and infused to the patient either immediately or after washing 3 times in normal saline supplemented with 6% anticoagulant citrate dextrose solution. Cell count with viability, clonogenic assay, and phenotyping were performed before and after thawing and after washing. Hematologic recovery, side effects, and complications were recorded. The in vitro and clinical data on 56 patients show that the depletion of DMSO in vitro before autografting does not induce a significant loss of cell number, viability, colony-forming unit-granulocyte-macrophage activity, or number of CD34(+) cells. Furthermore, it leads to a safe and sustained engraftment. The complications and side effects, as recorded by continuous monitoring, were substantially less; however, the procedure takes 3 to 4 hours of laboratory work per patient.
Assuntos
Neoplasias da Mama/terapia , Criopreservação , Dimetil Sulfóxido/efeitos adversos , Células-Tronco Hematopoéticas/citologia , Transplante de Células-Tronco de Sangue Periférico/métodos , Adolescente , Adulto , Neoplasias da Mama/complicações , Contagem de Células , Sobrevivência Celular , Feminino , Sobrevivência de Enxerto , Células-Tronco Hematopoéticas/efeitos dos fármacos , Humanos , Cinética , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Condicionamento Pré-Transplante/métodos , Transplante AutólogoRESUMO
The expression levels of a circulating extracellular domain of HER-2 can be detected in the plasma and serum of patients with metastatic breast cancer using an enzyme immunoassay (ELISA) method. In this study, we evaluated the clinical significance of high and low levels of HER-2 in the plasma of 46 patients with metastatic breast cancer enrolled in a clinical trial of high-dose chemotherapy (HDCT) using cyclophosphamide, mitoxantrone, and paclitaxel with autologous stem cell transplantation (ASCT). Using 2500 U/ml as the cut-point, 20 patients (46%) had elevated HER-2 levels (HER-2 positive). Our results suggest that patients with metastatic breast cancer and high soluble plasma HER-2 have a significantly poorer overall (OS) and progression-free survival (PFS) following high-dose chemotherapy with paclitaxel and ASCT. The median OS of patients with low levels of HER-2 was significantly longer (P < 0.01) than the median OS of patients with high levels of HER-2 (29.8 months vs 15.9 months). PFS was also significantly longer (P < 0.01) for patients who were HER-2-negative, than for patients who were HER-2-positive (13.0 vs 8.6 months). Univariate analysis showed that patients with liver or lung metastases had significantly reduced OS and PFS. Patients with metastases to two or more sites also had a significantly reduced time to disease progression, but not OS. In multivariable analysis, lung metastases contributed along with HER-2-positive status to determine a group of patients with significantly poorer OS. However, HER-2-positive status remained the only independent predictor of PFS.
Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Receptor ErbB-2/sangue , Adulto , Idoso , Análise de Variância , Biomarcadores Tumorais/sangue , Neoplasias da Mama/terapia , Progressão da Doença , Feminino , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/secundário , Pessoa de Meia-Idade , Proteínas de Neoplasias/sangue , Prognóstico , Indução de Remissão , Análise de SobrevidaRESUMO
The Fas/Fas ligand (FasL) system plays an important role in cellular apoptosis and is involved in cancer cell death induced by the immune system and anticancer drugs. Increased serum levels of soluble Fas (sFas) are associated with a number of different disease states and with tumor progression and metastasis in patients. In this study, we examined the plasma levels of sFas in 94 women with metastatic breast cancer undergoing high-dose chemotherapy (HDCT) treatment with autologous stem cell transplantation (ASCT) using a quantitative enzyme-linked immunosorbent assay (ELISA) method. Thirty-one patients (31/94, 33%) had plasma sFas levels greater than the optimum cut point of 1.90 ng/ml (median 2.47, range 1.98-13.54 ng/ml) and were designated as sFas positive. Sixty-three patients (63/94, 67%) had sFas levels below 1.90 ng/ml (median 1.14, range 0.47-1.89 ng/ml). In univariate analysis, patients with sFas-positive status, HER-2 overexpression, and the presence of liver metastases had a significantly shorter time to disease progression (PFS) and significantly decreased overall survival (OS). Multivariable analysis (Cox proportional hazards model) for PFS determined that sFas status significantly predicted disease progression (p = 0.004) with an adjusted hazard ratio (HR) of 2.0 (95% CI, 1.3-3.3). HER-2 status and liver metastases were also significant independent predictors of disease progression (p < 0.001) for both. sFas level was also an independent prognostic factor for OS with an adjusted HR of 2.0 (p = 0.006; 95% CI, 1.2-3.4). HER-2 status and liver metastases also remained highly significant independent prognostic factors for OS (HER-2: p < 0.001, HR 2.3, and liver metastases: p = 0.001, HR 2.7). In conclusion, these results suggest that plasma levels of sFas may be a valuable clinical prognostic factor in predicting outcome (PFS and OS) for patients with metastatic breast cancer undergoing HDCT with ASCT.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/patologia , Transplante de Células-Tronco , Receptor fas/sangue , Adulto , Análise de Variância , Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Pessoa de Meia-Idade , Prognóstico , Receptor ErbB-2/metabolismo , Estudos Retrospectivos , Solubilidade , Análise de Sobrevida , Transplante AutólogoRESUMO
C-erbB-2/HER-2 (designated HER-2) is overexpressed in both primary and metastatic breast cancer and predicts poor prognosis. We investigated the expression of HER-2 in patients with metastatic breast cancer undergoing high-dose chemotherapy (HDCT) with autologous blood stem cell (ABSC) support and correlated the presence (positive) or absence (negative) of HER-2 overexpression in these patients with response to treatment, progression-free survival (PFS) and overall survival (OS). The level of HER-2 expression was analyzed in 57 patients with metastatic breast cancer undergoing HDCT with ABSC support. Plasma from peripheral blood was taken at three different time points during the course of treatment and was analyzed using an enzyme immunoassay (EIA) to detect circulating levels of the extracellular portion of HER-2. HER-2 levels were elevated (>0.2 U/mg protein) in 27/57 (47.4%) patients at one or more time points during treatment. The level of HER-2 varied during the course of treatment. Following induction chemotherapy (ICT), five patients who were negative initially, showed overexpression of HER-2. Three patients overexpressed HER-2 only after HDCT/ABSC. Response to treatment was similar in patients independent of plasma HER-2 levels. Overexpression of HER-2 was associated with a significantly shorter PFS (P = 0.004, log rank) and OS (P = 0.003, log rank) after HDCT/ABSC. HER-2 overexpression, patient age, estrogen receptor status, progesterone receptor status, and previous hormone treatment were assessed by univariate and multivariate analysis. Univariate analysis determined that only HER-2 overexpression correlated significantly with decreases in progression free survival (P = 0.005, Cox regression). Decreased overall survival correlated significantly with HER-2 overexpression (P = 0.004) and decreased expression of both estrogen receptor (P = 0.032) and progesterone receptor (P = 0.039). In multivariate analysis of these variables, only HER-2 expression levels proved to be of independent statistical significance in predicting outcome for both PFS (P = 0.007) and OS (P = 0.002). These results suggest that overexpression of HER-2, measured by EIA in plasma may predict a shorter PFS and OS in patients with metastatic breast cancer treated with HDCT and ABSC support.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/terapia , Transplante de Células-Tronco Hematopoéticas , Receptor ErbB-2/análise , Adulto , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Terapia Combinada , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Epirubicina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Metástase Neoplásica , Estudos Retrospectivos , Análise de Sobrevida , Transplante AutólogoRESUMO
Although peripheral blood and bone marrow are usually readily available from patients, present techniques of RNA extraction are tedious, require millilitres of starting material and removal of red blood cells before RNA purification. Further, successful reverse transcriptase polymerase chain reaction (RT-PCR) amplification requires the removal of haemoglobin derivatives which interfere with the PCR process. Recently, one step rapid use reagents have become available, claiming to be useful for obtaining high quality RNA from microlitre quantities of whole blood drawn directly from the patient. Their use to date in clinical samples appears limited with little information in the literature documented. In an attempt to overcome this, we tested the Trizol-LS, RNA-STAT-50 and Ultraspec-3 reagents upon a statistically significant number of clinical isolates of fresh and cryopreserved peripheral blood, bone marrow, blood apheresis products and a breast cancer cell line (MCF7) in order to evaluate whether these methods could be applied to routine laboratory use in an RT-PCR method capable of detecting rare gene expression. Our findings showed that there was some variation in the quality of RNA extracted which was indicated by absorbance spectrophotometry at 260 and 280 nm. 1% agarose gel electrophoresis showed that each of these methods could yield total RNA capable of generating the signature 18S and 28S rRNA bands. Using the Kruskal-Wallis non-parametric anova test combined with Dunn's multiple comparison test, the only statistically significant difference (p<0.05) indicated that Trizol-LS was more reliable than RNA-STAT-50-LS and Ultraspec-3 at extracting RNA from fresh peripheral blood. RNA extracted with the Trizol-LS and RNA STAT-50 reagents was successfully amplified in a multiplex RT-PCR reaction for detection of the multi-drug resistance related genes MDR1, the multi-drug resistance related protein (MRP) and topoisomerase IIalpha. Low level MDR1 gene expression could be detected in frozen whole blood. However, PCR products were only seen when the anti-coagulant heparin was removed from all samples prior to cDNA production. RT-PCR amplification was not 100% successful with RNA extracted with Ultraspec-3 reagent. In conclusion, we found that the RNA extracted from whole blood with the Trizol-LS and the RNA-STAT-50 are suitable for use in clinically relevant molecular biology protocols that analyze rare event genes without further purification. Our results indicated that the Trizol-LS reagent was generally more consistent in obtaining a pure and sufficient quantity of RNA from patient material as shown by the mean result of purity and quantity in comparison to either Ultraspec-3 or RNA-STAT-50-LS reagents. Ultraspec-3 is not easily suited for direct use with whole blood products.
Assuntos
Reação em Cadeia da Polimerase/métodos , RNA/análise , Kit de Reagentes para Diagnóstico , Estudos de Avaliação como Assunto , Expressão Gênica , Humanos , Transcrição Gênica , Células Tumorais CultivadasRESUMO
BACKGROUND: Many patients with circulating antibodies to human leucocyte antigens (anti-HLA) are highly sensitised against renal transplantation and are liable to immediate graft loss through hyperacute rejection. Our aim was to find out whether removal of anti-HLA immediately before renal transplantation prevented hyperacute graft rejection. METHODS: 13 highly sensitised patients underwent cadaveric renal transplants immediately after immunoadsorption (IA) treatment to remove anti-HLA. Before IA, 12 patients had a positive crossmatch against donor cells either by cytotoxic or flow-cytometric assay; results for one patient were equivocal. FINDINGS: Renal biopsy samples were obtained 20 min after removal of the vascular clamps in nine patients. There was no evidence of hyperacute rejection in six of the nine patients; the other three patients showed glomerular thrombosis but no other evidence of hyperacute rejection. Two of these three grafts were functioning at 31 months of follow-up. Six episodes of acute rejection occurred in five patients during the first month after transplantation and overall there were 13 rejection episodes in nine patients. At latest follow-up (median 26 months, range 9-42), 12 of 13 patients were alive and seven of 13 grafts were surviving with a median plasma creatinine concentration of 185 mumol/L (range 106-296) in the functioning grafts. No graft was lost as a result of classic hyperacute rejection. INTERPRETATION: Immediate pretransplant IA can prevent hyperacute rejection and provide an opportunity for successful transplantation in highly sensitised patients.
Assuntos
Anticorpos Anti-Idiotípicos/sangue , Rejeição de Enxerto/prevenção & controle , Antígenos HLA/sangue , Transplante de Rim , Adolescente , Adulto , Criança , Reações Cruzadas , Feminino , Citometria de Fluxo , Rejeição de Enxerto/sangue , Rejeição de Enxerto/etiologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Transplant renal artery stenosis (TRAS) is a common complication after transplantation and is an important cause of graft dysfunction. Damage from graft rejection, trauma, and atherosclerosis have been implicated as possible causes. We reviewed all 917 patients transplanted in our unit since 1978 to study the prevalence, clinical features, and possible causes of TRAS. Seventy-seven patients with TRAS were identified. The detected incidence was 2.4% before the introduction of color doppler ultrasonography (CDU) and rose to 12.4% after CDU was introduced in 1985, giving an overall incidence of 8.4% during a mean follow-up period of 6.9 years. The TRAS group was compared with a control group of 77 transplanted patients matched for age, year of transplant, sex, and number of previous grafts. Mean ages for the study and control groups were 43.6 +/- 15 and 44.8 +/- 13.7 yr. A total of 25% of cases of TRAS were diagnosed within the first 8 wk of transplantation and in 60% within the first 30 wk (median = 23 wk). All patients were treated with angioplasty, 28 patients had recurrence of TRAS requiring multiple angioplasties (maximum 5) and 1 went on to have surgery. Angioplasty resulted in a significant fall in plasma creatinine. Patient and graft survival were significantly worse in the TRAS group: 69% vs. 83% (P < 0.05) and 56% vs. 74% (P < 0.05) (TRAS vs. Control), respectively. There was a significantly higher incidence of rejection, especially cellular rejection in the TRAS group, 0.67 vs. 0.35 episodes per patient (P < 0.01) (TRAS vs. Control). Recurrence but not occurrence of TRAS was associated with the use of cyclosporine.
Assuntos
Transplante de Rim/efeitos adversos , Obstrução da Artéria Renal/etiologia , Adulto , Feminino , Sobrevivência de Enxerto , Antígenos HLA/imunologia , Teste de Histocompatibilidade , Humanos , Transplante de Rim/imunologia , Masculino , Pessoa de Meia-Idade , Obstrução da Artéria Renal/diagnóstico por imagem , Obstrução da Artéria Renal/imunologia , Ultrassonografia Doppler em CoresRESUMO
We report a successful renal transplant in a highly sensitised paediatric recipient following removal of HLA-specific antibodies by extracorporeal immunoadsorption. The immediate pretransplant cytotoxic titre against the donor was greater than 1:512; this was reduced to negativity by two immunoadsorption sessions prior to transplant surgery. We also describe the presence of unexpected non-HLA-specific antibody activities in this immunoadsorbed patient.
Assuntos
Autoanticorpos , Rejeição de Enxerto/terapia , Antígenos HLA/imunologia , Transplante de Rim/imunologia , Diálise Renal/métodos , Criança , Rejeição de Enxerto/imunologia , Humanos , Imunoadsorventes , MasculinoRESUMO
Doppler ultrasound investigation was performed in the renal grafts of 86 patients with primary non-function following cadaveric renal transplantation. Pulsatility Index, defined as: [formula: see text] was assessed to examine its predictive use in the diagnosis of rejection episodes as judged by a retrospective analysis of histological data. Altogether 415 Doppler examinations and 228 renal biopsies were performed. In our population the incidence of rejection was 57%. Using a pulsatility index (PI) > 1.8 to be indicative of rejection, the sensitivity of our test was 68% for vascular rejection and 65% for all rejection episodes. The specificity was 25%. We conclude that Doppler ultrasound cannot replace the need for transplant renal biopsy in patients with primary non-function.
Assuntos
Rejeição de Enxerto/diagnóstico por imagem , Transplante de Rim , Rim/diagnóstico por imagem , Humanos , Rim/fisiopatologia , Necrose Tubular Aguda/diagnóstico por imagem , UltrassonografiaRESUMO
The influence of delayed graft function on renal allograft survival has been studied in a review of 322 renal transplants performed at one pediatric institution. The appearance of the first radionuclide renal scan was used to indicate early function in patients receiving their first cadaveric allograft. Patients whose first radionuclide renal scan showed both good renal perfusion and good function (n = 52) were compared with those whose scans demonstrated good perfusion but no function (n = 32). the actuarial graft survival of those with no function was significantly worse (P < .05). The difference in graft survival was not solely due to grafts lost in the early posttransplant period. Analysis of serial serum creatinine estimations suggests a process of continued inexorable nephron loss in some patients whose grafts showed a delay in achieving function.
Assuntos
Transplante de Rim , Adolescente , Criança , Pré-Escolar , Creatinina/sangue , Sobrevivência de Enxerto/fisiologia , Humanos , Lactente , Rim/diagnóstico por imagem , Rim/fisiologia , Cintilografia , Fatores de Tempo , Transplante HomólogoRESUMO
Between 1967 and 1989 in this unit 262 children (age at transplantation 9 months to 17 years, mean 9.6 years) had 345 renal transplants performed. Transplant artery stenosis (TAS) was found in 30 (8.7%) as demonstrated by arteriography, performed only when there was unexplained deterioration in transplant function, hypertension that was difficult to control, or in the presence of a vascular bruit. All patients with TAS except one had received a cadaveric allograft. From 1980 onward, percutaneous transluminal angioplasty (PTA) has been available for TAS, and this was attempted on 21 occasions in 16 patients. Nine patients demonstrated angiographic improvement following the procedure, and 7 showed immediate clinical improvement. On one occasion angioplasty precipitated graft loss. Five patients underwent planned corrective surgery, 4 after unsuccessful angioplasties. Our experience suggests that PTA should be the first method of intervention for TAS. Moderate success, both in angiographic and clinical terms, can be achieved, negating the need for surgery, while failure of PTA does not preclude surgical attempts at correction.
Assuntos
Angioplastia com Balão , Transplante de Rim/efeitos adversos , Obstrução da Artéria Renal/terapia , Adolescente , Angiografia , Anti-Hipertensivos/uso terapêutico , Criança , Pré-Escolar , Rejeição de Enxerto , Humanos , Hipertensão Renovascular/tratamento farmacológico , Lactente , Transplante de Rim/imunologia , Nefrectomia , Obstrução da Artéria Renal/etiologia , Transplante HomólogoRESUMO
In a blind trial, 77 patients were randomised to receive first cadaver kidney allografts that had been perfused either with a pair of CD45 monoclonal antibodies (mAbs), in an attempt to reduce the immunogenicity of passenger leucocytes, or with control human albumin solution. No complications of mAb perfusion were observed. Patient and allograft survival were similar in both groups. Rejection episodes were recorded in 7 (18%) of the patient with mAb perfused allografts compared with 24 (63%) of the controls.
Assuntos
Antígenos de Diferenciação/administração & dosagem , Rejeição de Enxerto/efeitos dos fármacos , Antígenos de Histocompatibilidade/administração & dosagem , Transplante de Rim/métodos , Perfusão/métodos , Pré-Medicação , Animais , Creatinina/sangue , Células Dendríticas/metabolismo , Estudos de Avaliação como Assunto , Humanos , Terapia de Imunossupressão/métodos , Incidência , Antígenos Comuns de Leucócito , Ensaios Clínicos Controlados Aleatórios como Assunto , Ratos , Transplante HomólogoAssuntos
Anticorpos Monoclonais/uso terapêutico , Antígenos de Diferenciação/imunologia , Rejeição de Enxerto , Antígenos de Histocompatibilidade/imunologia , Transplante de Rim , Glicoproteínas de Membrana/imunologia , Anticorpos Monoclonais/imunologia , Transporte Biológico , Feminino , Humanos , Rim/imunologia , Antígenos Comuns de Leucócito , Masculino , Pessoa de Meia-Idade , Transplante HomólogoRESUMO
Transplantation of kidneys bearing HLA antigens to which recipients have previously been exposed is generally avoided, and such prudence is a well-documented means of preventing early graft loss. Prior exposure and subsequent reactions can, however, take a wide variety of forms, and blanket avoidance may prevent many deserving patients from being transplanted. In our region, operating through a single tissue-typing laboratory, we follow a consistent policy of allowing retransplantation with kidneys bearing previous mismatches, provided no relevant antibody response has been detected. Twenty-one of 34 such transplants remain functioning at time periods ranging from 7 months to 7 years. Four were lost due to rejection within the 1st month, and the remaining 9 functioned for periods ranging from 2 months to 8 years. Three were lost for reasons other than rejection. Our antibody screening policy and our criteria for a negative crossmatch results in the exclusion of two-thirds of all repeat mismatch transplantations. The results indicate that in the remaining third, transplantation can be performed across a repeat mismatch with excellent long-term results, provided our defined crossmatch policy is adhered to strictly.
Assuntos
Antígenos HLA-A , Antígenos HLA-B , Transplante de Rim , Soro Antilinfocitário/uso terapêutico , Sobrevivência de Enxerto , Teste de Histocompatibilidade , Humanos , Isoanticorpos/biossíntese , Reoperação , Fatores de TempoRESUMO
Twenty needle biopsies from 14 patients were taken at times of renal dysfunction, and frozen sections were stained for class I and class II major histocompatibility complex (MHC) antigen expression using the immunoperoxidase technique and monomorphic mouse monoclonal antibodies. Eight of the 9 biopsies taken during periods of dysfunction attributed to cyclosporine toxicity had normal levels of class II expression. In contrast, 9 of the 10 biopsies taken during episodes of rejection had easily recognized increases in class II expression. In the one case where no definite clinical diagnosis was possible, no class II induction was present. Class I levels were less definitive but tended to be markedly raised in the cases of rejection, and only mildly raised in the cases of nephrotoxicity. Biopsy results can be available within 1 1/2-2 hr. The test is therefore likely to be of value in the correct diagnosis of the cause of renal dysfunction and thereby improve the management of cyclosporine-treated renal transplant patients.
Assuntos
Ciclosporinas/toxicidade , Rejeição de Enxerto , Antígenos HLA/análise , Antígenos HLA-D/análise , Transplante de Rim , Anticorpos Monoclonais , Biópsia por Agulha , Diagnóstico Diferencial , Humanos , Rim/efeitos dos fármacos , Rim/patologia , Túbulos Renais/imunologia , Leucócitos/patologia , Fatores de TempoRESUMO
Erythrocyte superoxide dismutase, glutathione peroxidase and catalase activities have been measured in patients with untreated malignant lymphomas. Marked deficiencies of superoxide dismutase (P less than 0.001) and glutathione peroxidase (P less than 0.001) were found, whereas catalase levels were normal. There was no apparent difference in enzyme activities between the different histological types of lymphoma.