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1.
J Intern Med ; 290(2): 359-372, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33576075

RESUMO

BACKGROUND: Characteristics and prognosis of patients admitted with strong suspicion of myocardial infarction (MI) but discharged without an MI diagnosis are not well-described. OBJECTIVES: To compare background characteristics and cardiovascular outcomes in patients discharged with or without MI diagnosis. METHODS: The DETermination of the role of Oxygen in suspected Acute Myocardial Infarction (DETO2X-AMI) trial compared 6629 patients with strong suspicion of MI randomized to oxygen or ambient air. The main composite end-point of this subgroup analysis was the incidence of all-cause death, rehospitalization with MI, heart failure (HF) or stroke during a follow-up of 2.1 years (median; range: 1-3.7 years) irrespective of randomized treatment. RESULTS: 1619 (24%) received a non-MI discharge diagnosis, and 5010 patients (76%) were diagnosed with MI. Groups were similar in age, but non-MI patients were more commonly female and had more comorbidities. At thirty days, the incidence of the composite end-point was 2.8% (45 of 1619) in non-MI patients, compared to 5.0% (250 of 5010) in MI patients with lower incidences in all individual end-points. However, for the long-term follow-up, the incidence of the composite end-point increased in the non-MI patients to 17.7% (286 of 1619) as compared to 16.0% (804 of 5010) in MI patients, mainly driven by a higher incidence of all-cause death, stroke and HF. CONCLUSIONS: Patients admitted with a strong suspicion of MI but discharged with another diagnosis had more favourable outcomes in the short-term perspective, but from one year onwards, cardiovascular outcomes and death deteriorated to a worse long-term prognosis.


Assuntos
Insuficiência Cardíaca/epidemiologia , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/mortalidade , Readmissão do Paciente , Acidente Vascular Cerebral/epidemiologia , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Alta do Paciente , Prognóstico , Taxa de Sobrevida
2.
BMC Genet ; 21(1): 104, 2020 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-32928105

RESUMO

BACKGROUND: Prebreeding in plants is the activity designed to identify useful characteristics from wild germplasm and its integration in breeding programs. Prebreeding aims to introduce new variation into the populations of a species of interest. Pedigree analysis is a valuable tool for evaluation of variation in genebanks where pedigree maps are used to visualize and describe population structure and variation within these populations. Margot Forde Germplasm Centre (MFGC) is New Zealand's national forage genebank and holds a collection of ~ 75 species of the genus Trifolium, of which only a dozen have been taken through prebreeding programs. The main objective of this study was to construct pedigree maps and analyse patterns of relatedness for seven minor Trifolium species accessions contained at the MFGC. These species are Trifolium ambiguum, Trifolium arvense, Trifolium dubium, Trifolium hybridum, Trifolium medium, Trifolium subterraneum and the Trifolium repens x Trifolium occidentale interspecific hybrids. We present a history of Trifolium spp. prebreeding in New Zealand and inform breeders of possible alternative forage species to use. RESULTS: Pedigree data from accessions introduced between 1950 and 2016 were used and filtered based on breeding activity. Kinship levels among Trifolium spp. remained below 8% and no inbreeding was found. Influential ancestors that contributed largely to populations structure were identified. The Australian cultivar 'Monaro' had a strong influence over the whole population of accessions in T. ambiguum. T. subterraneum and T. repens x T. occidentale had the largest number of generations (3). T. ambiguum and T. medium had the highest cumulative kinship across the decades. CONCLUSIONS: We conclude that there are high levels of diversity in the seven Trifolium spp. studied. However, collection and prebreeding efforts must be strengthened to maximize utilization and bring useful genetic variation.


Assuntos
Genética Populacional , Linhagem , Melhoramento Vegetal , Trifolium/genética , Variação Genética , Genoma de Planta , Endogamia , Nova Zelândia , Trifolium/classificação
3.
Am J Transplant ; 18(8): 2079-2082, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29719109

RESUMO

Impaired fertility is common among patients with chronic organ failure, including end-stage renal disease (ESRD). Women of childbearing age undergoing transplantation may experience rapid return of fertility. Pregnancy posttransplant presents numerous risks for the patient, fetus, and allograft. Maternal risks include hypertension and preeclampsia. Allograft risks include acute rejection and failure of the organ, and fetal risks include miscarriage, birth defects from immunosuppressants, premature delivery, and low birth weight. Belatacept, a selective T cell costimulation blocker, was approved for use in kidney transplant recipients in the United States in 2011. Little is known about the safety of belatacept during pregnancy in humans. We describe 2 cases of successful pregnancy and delivery with the use of belatacept-based immunosuppression. The Transplant Pregnancy Registry International (TPR) is a voluntary registry for transplant recipients who have had pregnancies or fathered a pregnancy posttransplant. To date, these 2 cases are the only known exposures to belatacept that have been reported to the TPR.


Assuntos
Abatacepte/uso terapêutico , Rejeição de Enxerto/tratamento farmacológico , Sobrevivência de Enxerto/efeitos dos fármacos , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Adulto , Feminino , Idade Gestacional , Taxa de Filtração Glomerular , Rejeição de Enxerto/etiologia , Humanos , Imunossupressores/uso terapêutico , Recém-Nascido , Gravidez , Resultado da Gravidez , Transplantados
4.
J Intern Med ; 283(4): 334-345, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29226465

RESUMO

BACKGROUND: Oxygen therapy has been used routinely in normoxemic patients with suspected acute myocardial infarction (AMI) despite limited evidence supporting a beneficial effect. AMI is associated with a systemic inflammation. Here, we hypothesized that the inflammatory response to AMI is potentiated by oxygen therapy. METHODS: The DETermination of the role of Oxygen in suspected Acute Myocardial Infarction (DETO2X-AMI) multicentre trial randomized patients with suspected AMI to receive oxygen at 6 L min-1 for 6-12 h or ambient air. For this prespecified subgroup analysis, we recruited patients with confirmed AMI from two sites for evaluation of inflammatory biomarkers at randomization and 5-7 h later. Ninety-two inflammatory biomarkers were analysed using proximity extension assay technology, to evaluate the effect of oxygen on the systemic inflammatory response to AMI. RESULTS: Plasma from 144 AMI patients was analysed whereof 76 (53%) were randomized to oxygen and 68 (47%) to air. Eight biomarkers showed a significant increase, whereas 13 were decreased 5-7 h after randomization. The inflammatory response did not differ between the two treatment groups neither did plasma troponin T levels. After adjustment for increase in troponin T over time, age and sex, the release of inflammation-related biomarkers was still similar in the groups. CONCLUSIONS: In a randomized controlled setting of normoxemic patients with AMI, the use of supplemental oxygen did not have any significant impact on the early release of systemic inflammatory markers.


Assuntos
Infarto do Miocárdio sem Supradesnível do Segmento ST/terapia , Oxigenoterapia/efeitos adversos , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Síndrome de Resposta Inflamatória Sistêmica/etiologia , Idoso , Biomarcadores/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico
5.
Ann Bot ; 118(4): 699-710, 2016 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-27208735

RESUMO

Background and aims Traits related to root depth distribution were examined in Trifolium repens × T. uniflorum backcross 1 (BC1) hybrids to determine whether root characteristics of white clover could be improved by interspecific hybridization. Methods Two white clover cultivars, two T. uniflorum accessions and two BC1 populations were grown in 1 -m deep tubes of sand culture. Maximum rooting depth and root mass distribution were measured at four harvests over time, and root distribution data were fitted with a regression model to provide measures of root system shape. Morphological traits were measured at two depths at harvest 3. Key Results Root system shape of the hybrids was more similar to T. uniflorum than to white clover. The hybrids and T. uniflorum had a higher rate of decrease in root mass with depth than white clover, which would result in higher proportions of root mass in the upper profile. Percentage total root mass at 100-200 mm depth was higher for T. uniflorum than white clover, and for Crusader BC1 than 'Crusader'. Roots of the hybrids and T. uniflorum also penetrated deeper than those of white clover. T. uniflorum had thicker roots at 50-100 mm deep than the other entries, and more of its fine root mass at 400-500 mm. The hybrids and white clover had more of their fine root mass higher in the profile. Consequently, T. uniflorum had a higher root length density at 400-500 mm than most entries, and a smaller decrease in root length density with depth. Conclusions These results demonstrate that rooting characteristics of white clover can be altered by hybridization with T. uniflorum, potentially improving water and nutrient acquisition and drought resistance. Root traits of T. uniflorum are likely to be adaptations to soil moisture and fertility in its natural environment.

6.
J Environ Qual ; 45(6): 1960-1969, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27898779

RESUMO

Land application of biosolids to low-fertility soil can improve soil quality by increasing concentrations of macronutrients and trace elements. Mixing biosolids with sawdust could reduce the risks of contaminant accumulation posed by rebuilding soils using biosolids alone. We aimed to determine the effects of biosolids and biosolids-sawdust on the plant quality and chemical composition of sorghum, rapeseed, and ryegrass. Plants were grown in a greenhouse over a 5-mo period in a low-fertility soil amended with biosolids (1250 kg N ha), biosolids-sawdust (0.5:1), or urea (200 kg N ha). Biosolids application increased the biomass of sorghum, rapeseed, and ryegrass up to 14.0, 11.9, and 4.1 t ha eq, respectively. Mixing sawdust with biosolids resulted in a growth response similar to biosolids treatments in rapeseed but nullified the effect of biosolids in sorghum. Urea fertilization provided insufficient nutrients to promote rapeseed growth and seed production, whereas seed yields after biosolids application were 2.5 t ha. Biosolids and biosolids-sawdust application enhanced plant quality by increasing element concentrations, especially Zn, and potentially toxic elements (Cd, Cr, Ni) did not exceed food safety standards. An application of 50 t ha of biosolids, equivalent to 1250 kg N ha, did not exceed current soil limits of Cu, Zn, and Cd and hence was effective in rebuilding soil without accumulating contaminants. The effect of mixing sawdust with biosolids varies with plant species but can further enhance plant nutrient quality in biomass and seeds, especially P, Cu, Zn, Mn, Fe, S, and Na.


Assuntos
Produtos Agrícolas , Metais Pesados , Poluentes do Solo , Biomassa , Solo
7.
BMC Urol ; 15: 56, 2015 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-26126393

RESUMO

BACKGROUND: To measure the effects of real-time visualisation during urethrocystoscopy on pain in patients who underwent ambulatory urethrocystoscopy. METHODS: An observational study was designed. From June 2012 to June 2013 patients who had ambulatory urethrocystoscopy participated in the study. In order to measure pain perception we used a numeric rating scale (NRS) 0 to 10. Additional data was collected including gender, reason for intervention, use of a rigid or a flexible instrument and whether the patient had had urethrocystoscopy before. RESULTS: 185 patients were evaluated. 125 patients preferred to watch their urethrocystoscopy on a real-time video screen, 60 patients did not. There was no statistically relevant difference in pain perception between those patients who watched their urethrocystoscopy on a real-time video screen and those who did not (p = 0.063). However, men who were allowed to watch their flexible urethrocystoscopy experienced significantly less pain, than those who did not (p = 0.007). No such effects could be measured for rigid urethrocystoscopy (p = 0.317). Furthermore, women experienced significantly higher levels of pain during the urethrocystoscopy than men (p = 0.032). CONCLUSIONS: Visualisation during urethrocystoscopy procedures in general does not significantly decrease pain in patients. Nevertheless, men who undergo flexible urethrocystoscopy should be offered to watch their procedure in real-time on a video screen. To make urethrocystoscopy less painful for both genders, especially for women, should be subject to further research.


Assuntos
Biorretroalimentação Psicológica/métodos , Cistoscopia/efeitos adversos , Cistoscopia/métodos , Dor/etiologia , Dor/prevenção & controle , Participação do Paciente/métodos , Adolescente , Adulto , Idoso , Assistência Ambulatorial/métodos , Retroalimentação Sensorial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/diagnóstico , Manejo da Dor/métodos , Medição da Dor , Participação do Paciente/psicologia , Resultado do Tratamento , Doenças da Bexiga Urinária/complicações , Doenças da Bexiga Urinária/patologia , Doenças da Bexiga Urinária/psicologia , Adulto Jovem
8.
Clin Med Res ; 13(2): 89-93, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25487240

RESUMO

Traumatic brain injury and intracranial hypertension often require treatment to optimize patient outcome. There are a variety of complex medical conditions that can preclude standard approaches to the treatment of intracranial hypertension. We describe a case where a novel approach using continuous dialysis with trisodium citrate was used to optimize the outcome of a young male with acute renal failure and acute respiratory distress syndrome in the setting of acute traumatic brain injury.


Assuntos
Injúria Renal Aguda/terapia , Anticoagulantes/uso terapêutico , Lesões Encefálicas/terapia , Citratos/uso terapêutico , Hipernatremia/induzido quimicamente , Pressão Intracraniana , Terapia de Substituição Renal/métodos , Injúria Renal Aguda/complicações , Adolescente , Anticoagulantes/farmacologia , Lesões Encefálicas/complicações , Citratos/farmacologia , Terapia Combinada , Humanos , Masculino , Síndrome do Desconforto Respiratório/complicações , Síndrome do Desconforto Respiratório/terapia
9.
Andrologia ; 47(2): 153-9, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24528255

RESUMO

Macrophage metalloelastase-12 (MMP-12), a protein of the matrix metalloproteinase family, is involved in the breakdown of extracellular matrix in normal physiological processes as well as in disease processes. MMP-12 is almost exclusively produced by macrophages and is associated with inflammatory disorders. Giving the fact that inflammation negatively influences ejaculate parameters, we investigated a possible presence and correlation of MMP-12 in seminal plasma with parameters of the ejaculate, especially in leucocytospermic ejaculates. Forty-two patients who presented for semen analysis were assigned into four groups depending on the result of semen analysis according to the WHO guidelines 2010: normozoospermia (n = 11), OAT (n = 10), azoospermia (n = 10) and leucocytospermia (>1 mio. peroxidase-positive cells per ml) (n = 11). MMP-12 was detected by ELISA and was measurable in nearly all seminal plasma samples. Generally, MMP-12 concentrations were significantly higher in leucocytospermic samples than in nonleucocytospermic ones (P = 0.001). The MMP-12 levels between the latter nonleucocytospermic groups did not differ. Moreover, MMP-12 levels correlated with the presence of peroxidase-positive leucocytes. No correlation with CD 14 positive monocytes/macrophages was detected. In this study, we demonstrate that MMP-12 is present in seminal plasma and is correlated with inflammatory conditions in human semen and therefore may serve as predictor of ongoing inflammatory processes.


Assuntos
Doenças dos Genitais Masculinos/diagnóstico , Doenças dos Genitais Masculinos/metabolismo , Metaloproteinase 12 da Matriz/metabolismo , Análise do Sêmen , Sêmen/metabolismo , Adulto , Biomarcadores/metabolismo , Doenças dos Genitais Masculinos/patologia , Humanos , Inflamação/diagnóstico , Inflamação/metabolismo , Leucócitos/metabolismo , Leucócitos/patologia , Receptores de Lipopolissacarídeos/metabolismo , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Peroxidase/metabolismo , Valor Preditivo dos Testes
10.
Water Sci Technol ; 72(7): 1111-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26398026

RESUMO

Computational fluid dynamics (CFD) models of dissolved air flotation (DAF) have shown formation of stratified flow (back and forth horizontal flow layers at the top of the separation zone) and its impact on improved DAF efficiency. However, there has been a lack of experimental validation of CFD predictions, especially in the presence of solid particles. In this work, for the first time, both two-phase (air-water) and three-phase (air-water-solid particles) CFD models were evaluated at pilot scale using measurements of residence time distribution, bubble layer position and bubble-particle contact efficiency. The pilot-scale results confirmed the accuracy of the CFD model for both two-phase and three-phase flows, but showed that the accuracy of the three-phase CFD model would partly depend on the estimation of bubble-particle attachment efficiency.


Assuntos
Ar , Hidrodinâmica , Modelos Teóricos , Poluentes da Água/isolamento & purificação , Purificação da Água/métodos , Floculação , Tamanho da Partícula , Projetos Piloto , Solubilidade , Poluentes da Água/química
11.
Kidney Int ; 84(4): 810-7, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23657143

RESUMO

Serum ß(2)-microglobulin (ß(2)M), a novel marker of kidney function, predicts mortality and kidney failure in the general population, and its elevation following transplantation is a marker of acute rejection. The association between post-transplant serum ß(2)M and outcomes following kidney transplantation, however, is unknown. To help determine this, we conducted a retrospective cohort study of 2190 individuals receiving a primary kidney transplant with serum ß(2)M measured at discharge. A total of 452 deaths and 347 graft failures before death (669 total graft losses) occurred over a median of 4.1 years of follow-up. After adjustment, the highest quintile of ß(2)M (5.0 mg/l and above), compared with the lowest quintile (<2.3 mg/l), was associated with a hazard ratio of 4.6 (95% confidence interval 2.8, 7.5) for death, 4.1 (2.4, 7.0) for death-censored graft loss, and 3.8 (2.5, 5.6) for total graft loss. Serum ß(2)M was more strongly associated with each outcome than was serum creatinine. Higher serum ß(2)M at discharge was independently associated with each outcome in models stratified by the presence of delayed graft function, donor type, or estimated glomerular filtration rate at discharge. Thus, serum ß(2)M at discharge is a potent predictor of long-term mortality and graft loss in kidney transplant recipients, providing information on allograft function beyond that of serum creatinine.


Assuntos
Rejeição de Enxerto/epidemiologia , Transplante de Rim/mortalidade , Alta do Paciente , Microglobulina beta-2/sangue , Adulto , Biomarcadores/sangue , Estudos de Coortes , Creatinina/sangue , Feminino , Seguimentos , Humanos , Nefropatias/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
12.
Kidney Int ; 83(6): 1185-92, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23447068

RESUMO

In order to define the intensity of immunosuppression, we examined risk factors for acute rejection in desensitization protocols that use baseline donor-specific antibody levels measured as mean fluorescence intensity (MFImax). The study included 146 patients transplanted with a negative flow crossmatch and a mean follow-up of 18 months with the majority (83%) followed for at least 1 year. At the time of transplant, mean-calculated panel-reactive antibody and MFImax ranged from 10.3-57.2% and 262-1691, respectively, between low- and high-risk protocols. Mean MFImax increased significantly from transplant to 1 week and 1 year. The incidence of acute rejection (mean 1.65 months) as a combination of clinical and subclinical rejection was 32%, including 14% cellular, 12% antibody-mediated, and 6% mixed rejection. In regression analyses, only C4d staining in post-reperfusion biopsies (hazard ratio 3.3, confidence interval 1.71-6.45) and increased specific antibodies at 1-week post transplant were significant predictors of rejection. A rise in MFImax by 500 was associated with a 2.8-fold risk of rejection. Thus, C4d staining in post-reperfusion biopsies and an early rise in donor specific antibodies after transplantation are risk factors for rejection in moderately sensitized patients.


Assuntos
Complemento C4b/metabolismo , Rejeição de Enxerto/imunologia , Histocompatibilidade , Isoanticorpos/sangue , Transplante de Rim/efeitos adversos , Rim/imunologia , Fragmentos de Peptídeos/metabolismo , Doadores de Tecidos , Doença Aguda , Adulto , Biomarcadores/metabolismo , Biópsia , Distribuição de Qui-Quadrado , Feminino , Rejeição de Enxerto/patologia , Rejeição de Enxerto/fisiopatologia , Rejeição de Enxerto/prevenção & controle , Teste de Histocompatibilidade , Humanos , Imunossupressores/uso terapêutico , Estimativa de Kaplan-Meier , Rim/efeitos dos fármacos , Rim/patologia , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Regulação para Cima
13.
Transplantation ; 107(9): 2047-2054, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37287109

RESUMO

BACKGROUND: Posttransplant fertility returns quickly, and female recipients of child-bearing age may conceive while on immunosuppression. However, pregnancy after transplantation confers risks to the recipient, transplant, and fetus, including gestational hypertension, preeclampsia, gestational diabetes, transplant dysfunction, preterm labor, and low birthweight infants. Additionally, mycophenolic acid (MPA) products are teratogenic. Literature evidence regarding belatacept, a selective T-cell costimulation blocker, during pregnancy and while breastfeeding is extremely limited. When female transplant recipients on a belatacept-based regimen are desirous of pregnancy or at the time of conception, transplant providers manage the immunosuppression regimen in 1 of 2 ways: (1) switch both belatacept and MPA to a calcineurin inhibitor-based regimen with or without azathioprine, which is the more common practice but requires several modifications, having potential negative outcomes; or (2) only switch MPA to azathioprine while continuing belatacept. METHODS: This case series includes 16 pregnancies in 12 recipients with exposure to belatacept throughout pregnancy and while breastfeeding. Patient information was obtained from several sources, including Transplant Pregnancy Registry International, providers at Emory University, and Columbia University, as well as literature review. RESULTS: Pregnancy outcomes included 13 live births and 3 miscarriages. No birth defects or fetal deaths were reported in any of the live births. Seven infants were breastfed while their mothers continued belatacept. Outcomes appear comparable to those documented with the administration of calcineurin inhibitors. CONCLUSIONS: This case series provides data supporting the continued administration of belatacept during pregnancy. Additional research will assist in developing better guidelines to counsel female transplant recipients on belatacept desiring to pursue pregnancy.


Assuntos
Transplante de Rim , Transplantados , Gravidez , Recém-Nascido , Humanos , Feminino , Abatacepte/efeitos adversos , Azatioprina , Transplante de Rim/efeitos adversos , Rejeição de Enxerto , Imunossupressores/efeitos adversos , Inibidores de Calcineurina , Resultado da Gravidez , Ácido Micofenólico
14.
Water Res X ; 19: 100183, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-37292177

RESUMO

This paper reports conclusions from a recent study completed for the Water Research Foundation and the State of California to offer guidance on UV-chlorine advanced oxidation for potable water reuse. The fundamentals of UV-chlorine advanced oxidation are discussed, and lessons learned from some of the early adopters of this technology are presented. Important highlights include the significant impact of ammonia and chloramines on UV-chlorine treatment, challenges associated with predicting UV-chlorine performance due to complex photochemistry, and an ongoing need to monitor potential byproducts and transformation products when employing any form of advanced oxidation for potable reuse.

15.
Transpl Int ; 25(5): 518-26, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22394259

RESUMO

Between 1 January 2002 and 31 December 2007, our center performed 1687 adult renal transplants. A retrospective analysis was performed to compare outcomes between patients receiving alemtuzumab (n = 632) and those receiving either basiliximab (n = 690) or thymoglobulin (n = 125). Patients receiving alemtuzumab were younger (49 vs. 51 years, P = 0.02), had fewer HLA matches (1.7 vs. 2.0, P < 0.0001), were more likely to have a cytomegalovirus (CMV) donor(+)/recipient(-) transplant (22% vs. 17%, P = 0.03) and were less likely to receive a living donor allograft (32% vs. 37%, P = 0.04). Alemtuzumab recipients were less likely to receive tacrolimus (35% vs. 47%, P < 0.0001). The 1-, 3-, and 5-year cumulative incidence of antibody-mediated rejection (AMR) in alemtuzumab-treated patients was 19%, 24%, and 27%, vs. 11%, 15%, and 18% for the other group (P < 0.0001). The 1-, 3-, and 5-year allograft survival in the alemtuzumab group was 88%, 75%, and 67%, vs. 91%, 82%, and 74% for the other group (P < 0.0001). Patient survival was equivalent. Alemtuzumab was an independent risk factor for living donor allograft loss (HR 2.0, P = 0.004), opportunistic infections (HR 1.3, P = 0.01), CMV infections (HR 1.6, P = 0.001), and AMR (HR 1.5, P = 0.002). The significantly worse graft survival in the alemtuzumab cohort may be due to the increased rates of AMR and infectious complications.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Transplante de Rim/métodos , Adulto , Alemtuzumab , Anticorpos Monoclonais/uso terapêutico , Soro Antilinfocitário/uso terapêutico , Basiliximab , Feminino , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto , Humanos , Imunossupressores/uso terapêutico , Infecções/etiologia , Estimativa de Kaplan-Meier , Transplante de Rim/efeitos adversos , Transplante de Rim/imunologia , Leucopenia/etiologia , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes de Fusão/uso terapêutico , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
16.
World J Urol ; 29(1): 121-6, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20512580

RESUMO

PURPOSE: To evaluate the efficacy and safety of WX-G250, a chimeric monoclonal antibody that binds to carboxy anhydrase IX, combined with low-dose interferon-alpha (LD-IFNα) in patients with progressive metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: Thirty-one patients, nephrectomized for the primary tumor, clear cell progressive mRCC, were enrolled to receive weekly infusions of WX-G250 (20 mg i.v.; week 2-12) combined with LD-IFNα (3 MIU s.c. 3 times/week; week 1-12). At week 16, patients were evaluated for response and stratified into two groups: (a) responders into the extended treatment group for an additional 6 weeks of treatment or (b) the progressive group with no further study treatment. RESULTS: Of the 31 treated patients, 26 were evaluable for response to treatment. Two patients showed partial remission and 14 patients had stable disease as assessed in week 16. One patient experienced partial remission resulting in a complete remission lasting at least 17 months. Nine patients had durable stable disease of 24 weeks or longer. Clinical benefit was obtained in 42% (11/26) patients. The median overall survival achieved was 30 months and the 2-year survival was 57%. Patients receiving extended treatment showed a significantly longer 2-year survival rate than discontinued patients (79 vs. 30%; P=0.0083). In general, treatment was well tolerated with little toxicity. CONCLUSION: Treatment with the antibody WX-G250 in combination with LD-IFNα is safe, well tolerated, led to clinically meaningful disease stabilization and demonstrated clinical benefit in this progressive mRCC patient population.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Interferon-alfa/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Idoso , Anticorpos Monoclonais/efeitos adversos , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/mortalidade , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Humanos , Interferon alfa-2 , Interferon-alfa/efeitos adversos , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Proteínas Recombinantes , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
17.
J Ren Nutr ; 20(6): 392-7, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20537920

RESUMO

OBJECTIVE: This research study was conducted to investigate whether serum albumin levels predict allograft/patient outcomes in the new era of transplant medicine and immunology. METHODS: The association of 1-year post-transplant serum albumin, and patient and graft outcomes was retrospectively analyzed in 500 kidney transplant recipients between 1998 and 2005. Albumin was used as a categorical and a continuous variable in univariate and multivariate Cox regression and Kaplan-Meier survival analyses. RESULTS: The average (±SE) age at transplant was 47 ± 12 years. Patients were followed up for 63.4 ± 28 months after transplant. There were 56 graft losses and 38 patient deaths. In univariate analysis, the following variables were associated with the composite endpoint of patient death or allograft loss: 1-year serum albumin (hazard ratio [HR] = 0.52, P = .0009), 1-year serum albumin <4.0 g/dL (HR = 1.81, P = .02), 1-year serum creatinine (HR = 3.55, P < .00001), angiotensin converting enzyme inhibitors or angiotensin receptor blockers use (HR = 1.61, P = .03), a history of previous transplant (HR = 1.54, P = .04), months of dialysis before transplant (HR = 1.01, P = .00003), type of transplant (deceased donor HR = 1.64, P = .02), and acute rejection (HR = 1.52, P = .0000003). Of these, multivariable Cox regression analyses retained 1-year serum albumin (HR = 1.4, P < .0001), serum creatinine (HR = 2.7, P < .0001), and acute rejection (HR = 1.7, P = .02) as significant predictors of patient/graft loss. CONCLUSION: One-year serum albumin is an independent predictor of poor outcomes in the contemporary era of transplant medicine and immunosuppression. Further studies are needed to separate the role of this biomarker in inflammation and nutrition in kidney transplant recipients.


Assuntos
Rejeição de Enxerto/mortalidade , Sobrevivência de Enxerto , Falência Renal Crônica/terapia , Transplante de Rim/imunologia , Albumina Sérica/análise , Adulto , Antagonistas de Receptores de Angiotensina/sangue , Inibidores da Enzima Conversora de Angiotensina/sangue , Biomarcadores , Creatinina/sangue , Feminino , Rejeição de Enxerto/imunologia , Humanos , Estimativa de Kaplan-Meier , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Estudos Retrospectivos , Transplante Homólogo , Resultado do Tratamento
18.
Diabetologia ; 52(7): 1369-80, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19418039

RESUMO

AIMS/HYPOTHESIS: We measured serum C-peptide (at least 0.167 nmol/l) in 54 of 141 (38%) patients with chronic type 1 diabetes and sought factors that might differentiate those with detectable C-peptide from those without it. Finding no differences, and in view of the persistent anti-beta cell autoimmunity in such patients, we speculated that the immunosuppression (to weaken autoimmune attack) and euglycaemia accompanying transplant-based treatments of type 1 diabetes might promote recovery of native pancreatic beta cell function. METHODS: We performed arginine stimulation tests in three islet transplant and four whole-pancreas transplant recipients, and measured stimulated C-peptide in select venous sampling sites. On the basis of each sampling site's C-peptide concentration and kinetics, we differentiated insulin secreted from the individual's native pancreatic beta cells and that secreted from allografted beta cells. RESULTS: Selective venous sampling demonstrated that despite long-standing type 1 diabetes, all seven beta cell allograft recipients displayed evidence that their native pancreas secreted C-peptide. Yet even if chronic immunosuppression coupled with near normal glycaemia did improve native pancreatic C-peptide production, the magnitude of the effect was quite small. CONCLUSIONS/INTERPRETATION: Some native pancreatic beta cell function persists even years after disease onset in most type 1 diabetic patients. However, if prolonged euglycaemia plus anti-rejection immunosuppressive therapy improves native pancreatic insulin production, the effect in our participants was small. We may have underestimated pancreatic regenerative capacity by studying only a limited number of participants or by creating conditions (e.g. high circulating insulin concentrations or immunosuppressive agents toxic to beta cells) that impair beta cell function.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 1 , Imunossupressores/uso terapêutico , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/transplante , Transplante das Ilhotas Pancreáticas , Adulto , Biomarcadores/sangue , Peptídeo C/sangue , Peptídeo C/metabolismo , Doença Crônica , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/cirurgia , Feminino , Veias Hepáticas , Humanos , Insulina/sangue , Insulina/metabolismo , Secreção de Insulina , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Transplante de Pâncreas , Veia Porta , Regeneração/fisiologia , Transplante Homólogo
19.
Plant Physiol Biochem ; 137: 213-221, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30802804

RESUMO

Biowastes are unwanted materials of biological origin. They include biosolids, dairy shed effluent, and sawdust. When applied to soil, biowastes can provide plant nutrients, but also introduce heavy metals, pathogens, or xenobiotics. Biowastes could improve degraded or low-fertility soils and generate revenue through the production of non-food products such as essential oils. We grew New Zealand native plants, manuka (Leptospermum scoparium J.R. Forst & G. Forst) and kanuka (Kunzea robusta de Lange & Toelken) in series of greenhouse experiments in low-to-medium-fertility soils (Bideford clay loam, Lismore stony silt loam, and Pawson silt loam) amended with either biosolids (up to 13500 kg N ha-1 equiv.), biosolids + sawdust (1:0.5-1250 kg N ha-1 equiv.) and dairy shed effluent (200 kg N ha-1 equiv.). Two types of biosolids from Kaikoura (KB) and Christchurch City Council (CB) were used in the experiments. CB (1500 kg N ha-1 equiv.) and dairy shed effluent (200 kg N ha-1 equiv.) increased the biomass of L. scoparium by up to 120% and 31%, and K. robusta by up to 170% and 34%, respectively. Adding sawdust to KB increased the biomass of L. scoparium and K. robusta although it offset the L. scoparium growth increase in the KB-only treatment. The growth response of K. robusta to biowastes was greater than L. scoparium with oil production in K. robusta increasing by up to 211% when 1500 kg N ha-1 equiv. of CB was applied to Lismore stony silt loam. Generally, the treatments had a negligible effect on oil concentration in all the soil types, except for the KB + sawdust treatment, which increased the oil concentration by 82%. Most of the EOs' major components were unaffected by biowaste addition in the soils, although some components increased in the Bideford clay loam following KB and KB + sawdust application. Biosolids increased foliar concentrations of Zn, Cu, and Cd, but these were below risk-threshold concentrations. Applying CB (up to 1500 kg N ha-1 equiv.) to low-fertility soils is recommended to establish ecosystems dominated by L. scoparium and K. robusta that annually would produce ca. 100 kg ha-1 of EOs worth US$ 26k and 24k, respectively. Adding sawdust to CB could have environmental benefits through reduction of N leaching. Field trials are warranted to elucidate critical ecological variables and production economics in biowaste management.


Assuntos
Fertilizantes , Kunzea/metabolismo , Leptospermum/metabolismo , Óleos Voláteis/metabolismo , Óleos de Plantas/metabolismo , Indústria de Laticínios , Kunzea/crescimento & desenvolvimento , Leptospermum/crescimento & desenvolvimento , Nova Zelândia , Folhas de Planta/química , Solo/química , Poluentes do Solo/análise , Resíduos Sólidos
20.
Mol Ecol ; 17(21): 4740-53, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18992001

RESUMO

New Zealand is diverse in alpine and subalpine environments, a consequence of Late Tertiary tectonic and climatic change. However, few studies have sought to evaluate the importance of these environments as abiotic drivers in the diversification of plant species. Of particular interest is the Late Tertiary radiation of Pachycladon, an endemic New Zealand genus of alpine cress. Here we report observations on genome-wide levels of differential expression measured in the habitats of two closely related species of Pachycladon with distinct altitudinal preferences. Using Arabidopsis microarrays, we have identified 310 predominantly hormone- and stress-response genes up-regulated in Pachycladon fastigiata and 324 genes up-regulated in Pachycladon enysii. Expression patterns for glucosinolate biosynthesis and hydrolysis genes (MAM1, MAM-I, MAM-D, AOP2, ESP, ESM1) as well as flavonoid biosynthesis genes (F3'H, FLS, FAH1) were found to be species specific. Predicted differences in flavonoid contents were partly confirmed by high performance liquid chromatography analysis. Differences in glucosinolate profiles and glucosinolate hydrolysis products obtained by high performance liquid chromatography and gas chromatography-mass spectrometry analysis, respectively, also supported inferences from expression analyses. Five glucosinolate chemotypes were matched to known Arabidopsis ecotypes, and the potential adaptive significance of these chemotypes has been discussed. Our findings, in contrast to expectations for evolution of the New Zealand flora, suggest that biotic drivers, such as plant-herbivore interactions, are likely to be as important as abiotic drivers in the diversification of Pachycladon.


Assuntos
Brassicaceae/genética , Evolução Molecular , Regulação da Expressão Gênica de Plantas , Genética Populacional , Brassicaceae/metabolismo , DNA de Plantas/genética , Perfilação da Expressão Gênica , Genes de Plantas , Genoma de Planta , Glucosinolatos/genética , Glucosinolatos/metabolismo , Nova Zelândia , Análise de Sequência com Séries de Oligonucleotídeos , Especificidade da Espécie , Transcrição Gênica
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