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1.
Proc Natl Acad Sci U S A ; 115(21): 5409-5414, 2018 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-29760089

RESUMO

Forecasts of long-run economic growth are critical inputs into policy decisions being made today on the economy and the environment. Despite its importance, there is a sparse literature on long-run forecasts of economic growth and the uncertainty in such forecasts. This study presents comprehensive probabilistic long-run projections of global and regional per-capita economic growth rates, comparing estimates from an expert survey and a low-frequency econometric approach. Our primary results suggest a median 2010-2100 global growth rate in per-capita gross domestic product of 2.1% per year, with a standard deviation (SD) of 1.1 percentage points, indicating substantially higher uncertainty than is implied in existing forecasts. The larger range of growth rates implies a greater likelihood of extreme climate change outcomes than is currently assumed and has important implications for social insurance programs in the United States.

3.
Am J Transplant ; 13(4): 961-970, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23432755

RESUMO

Rapid discontinuation of prednisone (RDP) has minimized steroid-related complications following kidney transplant (KT). This trial compares long-term (10-year) outcomes with three different maintenance immunosuppressive protocols following RDP in adult KT. Recipients (n=440; 73% living donor) from March 2001 to April 2006 were randomized into one of three arms: cyclosporine (CSA) and mycophenolate mofetil (MMF) (CSA/MMF, n=151); high-level tacrolimus (TAC, 8-12 µg/L) and low-level sirolimus (SIR, 3-7 µg/L) (TACH/SIRL, n=149) or low-level TAC (3-7 µg/L) and high-level SIR (8-12 µg/L) (TACL/SIR(H) , n=140). Median follow-up was ∼7 years. There were no differences between arms in 10-year actuarial patient, graft and death-censored graft survival or in allograft function. There were no differences in the 10-year actuarial rates of biopsy-proven acute rejection (30%, 26% and 20% in CSA/MMF, TACH/SIRL and TACL/SIRH) and chronic rejection (38%, 35% and 31% in CSA/MMF, TACH/SIRL and TACL/SIRH). Rates of new-onset diabetes mellitus were higher with TACH/SIRL (p=0.04), and rates of anemia were higher with TACH/SIRL and TACL/SIRH (p=0.04). No differences were found in the overall rates of 16 other post-KT complications. These data indicate that RDP-based protocol yield acceptable 10-year outcomes, but side effects differ based on the maintenance regimen used and should be considered when optimizing immunosuppression following RDP.


Assuntos
Terapia de Imunossupressão/métodos , Imunossupressores/uso terapêutico , Transplante de Rim/métodos , Prednisona/uso terapêutico , Adulto , Ciclosporina/uso terapêutico , Diabetes Mellitus Tipo 1/diagnóstico , Feminino , Humanos , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapêutico , Complicações Pós-Operatórias , Estudos Prospectivos , Sirolimo/uso terapêutico , Esteroides/uso terapêutico , Tacrolimo/uso terapêutico , Fatores de Tempo , Transplante Homólogo , Resultado do Tratamento
4.
Am J Transplant ; 11(10): 2132-43, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21812918

RESUMO

Single-antigen bead (SAB) testing permits reassessment of immunologic risk for kidney transplantation. Traditionally, high panel reactive antibody (PRA), retransplant and deceased donor (DD) grafts have been associated with increased risk. We hypothesized that this risk was likely mediated by (unrecognized) donor-specific antibody (DSA). We grouped 587 kidney transplants using clinical history and single-antigen bead (SAB) testing of day of transplant serum as (1) unsensitized; PRA = 0 (n = 178), (2) third-party sensitized; no DSA (n = 363) or (3) donor sensitized; with DSA (n = 46), and studied rejection rates, death-censored graft survival (DCGS) and risk factors for rejection. Antibody-mediated rejection (AMR) rates were increased with DSA (p < 0.0001), but not with panel reactive antibody (PRA) in the absence of DSA. Cell-mediated rejection (CMR) rates were increased with DSA (p < 0.005); with a trend to increased rates when PRA>0 in the absence of DSA (p = 0.08). Multivariate analyses showed risk factors for AMR were DSA, worse HLA matching, and female gender; for CMR: DSA, PRA>0 and worse HLA matching. AMR and CMR were associated with decreased DCGS. The presence of DSA is an important predictor of rejection risk, in contrast to traditional risk factors. Further development of immunosuppressive protocols will be facilitated by stratification of rejection risk by donor sensitization.


Assuntos
Rejeição de Enxerto , Transplante de Rim , Adulto , Autoanticorpos/imunologia , Feminino , Rejeição de Enxerto/imunologia , Humanos , Imunossupressores/administração & dosagem , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Análise de Sobrevida , Doadores de Tecidos
5.
Am J Transplant ; 10(2): 331-7, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20041863

RESUMO

Kidney donors, similar to the general population, are at risk for development of type 2 diabetes mellitus (T2DM). The course of donors who develop T2DM has not been studied. We surveyed 3777 kidney donors regarding the development of T2DM. Of the 2954 who responded, 154 developed T2DM 17.7 +/- 9.0 years after donation. The multivariable risk of development of T2DM was associated with type 1 DM in the recipient, male gender and body mass index >30 kg/m(2) at time of donation. Compared to age, gender, duration after donation and body mass index (BMI)-matched non-diabetic donor controls; diabetic donors were more likely to have hypertension (70.8% vs. 36.2%, p = 0.005), proteinuria (18.8% vs. 3.9%, p < 0.0001) but had a similar serum creatinine. eGFR change after T2DM development was -0.80 +/- 0.94 mL/min/year, -0.70 +/- 0.86 in nondiabetic donors with similar duration after donation and -0.61 +/- 0.76 mL/min/year in age, gender, BMI and duration after donation matched nondiabetic donor controls. These preliminary and short-term data demonstrate that factors associated with T2DM in kidney donors are similar to those in the general population and donors screened carefully at the time of donation do not appear to have an acceleration of diabetic kidney disease.


Assuntos
Diabetes Mellitus/etiologia , Rim , Doadores de Tecidos , Adolescente , Adulto , Índice de Massa Corporal , Creatinina/sangue , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/complicações , Feminino , Humanos , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , Proteinúria/complicações , Fatores de Risco , Adulto Jovem
6.
Am J Transplant ; 9(6): 1337-46, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19459828

RESUMO

Nonadherence (NA) is a difficult posttransplant problem that can lead to graft loss. A retransplant is controversial because of a fear of recurrent NA. We reviewed our center's data base and identified 114 kidney recipients who lost their graft to overt NA; of this group, 35 (31%) underwent a retransplant after a thorough reevaluation. We compared this NA retransplant group to a control group of second transplant recipients who did not lose their first graft to overt NA (non-NA) (n = 552). After 8 years of follow-up, we found no significant differences between the groups in actuarial graft or patient survival rates, renal function, or the incidence of biopsy-proven chronic rejection. However, 5 of 35 (14%) NA recipients versus 10 of 552 (2%) non-NA recipients lost their retransplant to NA (p = 0.0001). Twenty of 35 (57%) of the NA group exhibited repeat NA behavior after retransplant. We conclude that prior graft loss to NA is associated with increased graft loss to NA after retransplant. However, the majority of NA retransplant recipients did well-with overall long-term outcomes similar to those of the non-NA group. With careful patient selection and aggressive intervention, prior overt NA should not be an absolute contraindication to retransplantation.


Assuntos
Rejeição de Enxerto/etiologia , Transplante de Rim , Cooperação do Paciente , Reoperação , Adulto , Feminino , Sobrevivência de Enxerto/imunologia , Humanos , Transplante de Rim/imunologia , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Equipe de Assistência ao Paciente , Seleção de Pacientes , Obtenção de Tecidos e Órgãos , Resultado do Tratamento
7.
Am J Transplant ; 9(4): 825-34, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19353771

RESUMO

The outcome of pregnancy in kidney donors has generally been viewed to be favorable. We determined fetal and maternal outcomes in a large cohort of kidney donors. A total of 2102 women have donated a kidney at our institution; 1589 donors responded to our pregnancy surveys; 1085 reported 3213 pregnancies and 504 reported none. Fetal and maternal outcomes in postdonation pregnancies were comparable to published rates in the general population. Postdonation (vs. predonation) pregnancies were associated with a lower likelihood of full-term deliveries (73.7% vs. 84.6%, p = 0.0004) and a higher likelihood of fetal loss (19.2% vs. 11.3%, p < 0.0001). Postdonation pregnancies were also associated with a higher risk of gestational diabetes (2.7% vs. 0.7%, p = 0.0001), gestational hypertension (5.7% vs. 0.6%, p < 0.0001), proteinuria (4.3% vs. 1.1%, p < 0.0001) and preeclampsia (5.5% vs. 0.8%, p < 0.0001). Women who had both pre- and post-donation pregnancies were also more likely to have these adverse maternal outcomes in their postdonation pregnancies. In this large survey of previous living donors in a single center, fetal and maternal outcomes and pregnancy outcomes after kidney donation were similar to those reported in the general population, but inferior to predonation pregnancy outcomes.


Assuntos
Recém-Nascido Prematuro , Doadores Vivos/estatística & dados numéricos , Nefrectomia/efeitos adversos , Complicações na Gravidez/epidemiologia , Resultado da Gravidez , Aborto Espontâneo/epidemiologia , Feminino , Humanos , Hipertensão/epidemiologia , Incidência , Recém-Nascido , Minnesota/epidemiologia , Pré-Eclâmpsia/epidemiologia , Gravidez , Natimorto/epidemiologia
8.
Am J Transplant ; 8(11): 2410-9, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18925907

RESUMO

The ultimate goal of clinical transplantation is for the recipients to achieve long-term survival, with continuing graft function, that is equivalent to that of the age-matched general population. We studied subsequent outcome in kidney transplant recipients with 10 years of graft function. In all, 2202 kidney transplant recipients survived with graft function >10 years. For 10-year survivors, the actuarial 25-year patient survival rate for primary transplant living donor (LD) recipients was 57%; graft survival, 43%. For primary transplant deceased donor (DD) recipients, the actuarial 25-year patient survival rate was 39%; graft survival, 27%. The two major causes of late graft loss were death (with graft function) and chronic allograft nephropathy (tubular atrophy and interstitial fibrosis). The two major causes of death with function were cardiovascular disease (CVD) and malignancy. For nondiabetic recipients, the mean age at death with function from CVD was 54 +/- 13 years; for diabetic recipients, 53 +/- 7 years. By 20 years posttransplant, morbidity was common: >40% recipients had skin cancer (mean age for nondiabetic recipients, 53 +/- 13 years; for diabetics, 49 +/- 8 years), >10% had non-skin cancer (mean age for nondiabetic recipients, 53 +/- 16 years; for diabetics, 46 +/- 9 years), and >30% had CVD (mean age for nondiabetic recipients, 53 +/- 15 years; for diabetics, 47 +/- 9 years). We conclude that long-term transplant recipients have a high rate of morbidity and early mortality. As short-term results have improved, more focus is needed on long-term outcome.


Assuntos
Doenças Cardiovasculares/terapia , Sobrevivência de Enxerto , Nefropatias/terapia , Transplante de Rim/métodos , Adolescente , Adulto , Idoso , Doenças Cardiovasculares/complicações , Doença Crônica , Feminino , Humanos , Nefropatias/complicações , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Fatores de Risco , Resultado do Tratamento
9.
Am J Transplant ; 7(9): 2152-7, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17697261

RESUMO

In the cyclosporine era, reports on pediatric kidney transplant (KTx) patients with obstructive and reflux uropathy are limited by small numbers, short follow-up, and/or lack of control groups. Our single-center study evaluated long-term outcomes (patient and graft survival, urinary tract infections [UTIs], urologic complications) in a large cohort of KTx recipients (<20 years old). We matched our 117 study patients with obstructive and reflux uropathy with 117 controls whose KTx was needed for other reasons; all 234 underwent their KTx between April 25, 1984, and October 23, 2002. The mean age was 8.0 +/- 6.2 years; mean follow-up, 133 +/- 67 months. The urologic complication rate was higher in study patients (43%) than in controls (11%) (p < 0.0001), as was the UTI rate (45% vs. 2%; p < 0.0001). The metabolic acidosis and UTI rates were higher in study patients who did (vs. did not) undergo bladder augmentation (p < 0.0001). We found no significant difference between study patients and controls in patient or graft survival, acute or chronic rejection, or mean estimated glomerular filtration rates. Unique to our study is the finding of higher metabolic acidosis and UTI rates in study patients who underwent bladder augmentation.


Assuntos
Rejeição de Enxerto/epidemiologia , Transplante de Rim , Obstrução Ureteral/cirurgia , Obstrução do Colo da Bexiga Urinária/epidemiologia , Infecções Urinárias/epidemiologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Obstrução do Colo da Bexiga Urinária/etiologia , Infecções Urinárias/etiologia
10.
Am J Transplant ; 7(8): 1948-53, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17617858

RESUMO

Roughly 15% of kidney transplant recipients on a rapid discontinuation of prednisone (RDP) protocol have > or =1 episode of acute rejection (AR). One clinically important question is whether long-term maintenance steroids should be introduced in those recipients having AR. Of 842 adult kidney transplant recipients on an RDP protocol, 149 (17.7%) have had at least 1 AR episode. Of these, 51 (34%) started on maintenance prednisone (5 mg/day) after treatment of the AR, while 98 (66%) remained steroid free. Demographics for the two groups were similar. With mean follow-up of 26 months, 48 (32%) of the recipients have had a 2nd AR episode: 15 (29.4%) in those on maintenance steroids vs. 33 (33.7%) in those remaining steroid free (p = 0.12). Graft survival was not significantly different between the two groups. Multivariate analysis of risk factors for a 2nd episode found the histologic appearance of the initial AR episode to be the most significant risk factor. But, whether steroids were added to the maintenance regimen or not, also seemed to have an impact (RR = 2.1, p = 0.07). At present there is evidence to suggest that some SA patients should start on maintenance steroids after AR. However, longer follow-up with more patients is necessary.


Assuntos
Glucocorticoides/administração & dosagem , Rejeição de Enxerto/tratamento farmacológico , Sobrevivência de Enxerto/efeitos dos fármacos , Transplante de Rim , Prednisona/administração & dosagem , Doença Aguda , Adulto , Biópsia , Esquema de Medicação , Feminino , Seguimentos , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/patologia , Humanos , Incidência , Masculino , Análise Multivariada , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
11.
J Biomed Mater Res A ; 80(1): 175-83, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17019726

RESUMO

Fluorcanasite glass-ceramics were produced by controlled two stage heat-treatment of as-cast glasses. These glasses were modified from stoichiometric fluorcanasite composition by either adding P(2)O(5) or altering the molar ratios of Na(2)O and CaO. Commercial bioactive 45S5 Bioglass(R) was also prepared in-house to evaluate the relative in vitro biocompatibility of fluorcanasite glass-ceramics. The scanning electron microscopy (SEM) images showed that cells had colonized the surfaces of fluorcanasite glass-ceramics to form a confluent sheet. Quantitative MTT assay results were in good agreement with the qualitative SEM observations. It was concluded that incorporation of excess calcium oxide or P(2)O(5) in stoichiometric glass composition improved in vitro biocompatibility. Controlled heat-treatment further improved the biological response of cultured bone cells to modified fluorcanasite glass-ceramics when compared with their parent glasses. Ion release and pH data suggested a strong correlation between solubility (in particular, Na ion release) and biocompatibility. Reduced solubility, Na ion release, and related pH effects appeared to be the principal mechanisms responsible for improvement in in vitro biocompatibility.


Assuntos
Materiais Biocompatíveis , Regeneração Óssea , Substitutos Ósseos , Cerâmica , Teste de Materiais , Animais , Materiais Biocompatíveis/química , Substitutos Ósseos/química , Linhagem Celular Tumoral , Cerâmica/química , Íons/química , Microscopia Eletrônica de Varredura , Ratos , Sódio/química , Propriedades de Superfície
12.
J Dent ; 34(8): 533-8, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16530912

RESUMO

INTRODUCTION: Since their invention in the late 1960s, glass ionomer cements (GICs) have been used extensively in dentistry but recently they have also been utilised in ear nose and throat (ENT) surgery. Unfortunately, Al3+, a component of conventional ionomer glasses, has been linked to poor bone mineralisation and neurotoxicity. OBJECTIVE: The aim of the research was to modify a commercial ionomer glass composition by substituting Al2O3 with Fe2O3. METHODS: Glasses with the following molar compositions were fabricated: 4.5SiO2*3M2O3*XP2O5*3CaO*2CaF2 (M = Al or Fe, X = 0-1.5). The glasses were characterised using X-ray fluorescence (XRF) and X-ray powder diffraction (XRD). Cements were prepared using a standard ratio of; 1 g of glass powder: 0.2 g of dried polyacrylic acid: 0.3 g of 10% tartaric acid solution. Cement formation was assessed using a Gilmore needle and in vitro biocompatibility was investigated for novel cement formulations. RESULTS: XRF revealed that the Fe2O3-based glasses had Al2O3 contamination from the crucibles and also had undergone substantial F- losses. XRD gave peaks that corresponded to magnetite Fe3O4 (JCPDS # 19-629) in all compositions. Apatite Ca5(PO4)3(OH,F) (JCPDS # 15-876) was identified in P2O5 containing glasses. It was possible to fabricate cements from all of the Fe2O3-based ionomer glasses. Good in vitro biocompatibility was observed for the Fe2O3-based cements. CONCLUSION: Ionomer glasses may be prepared by entirely replacing Al2O3 with Fe2O3. Cement setting times appeared to be related to P2O5 content. Fe2O3-based cements showed good in vitro biocompatibility.


Assuntos
Compostos Férricos/toxicidade , Cimentos de Ionômeros de Vidro/química , Cimentos de Ionômeros de Vidro/toxicidade , Vidro/química , Animais , Linhagem Celular Tumoral , Forma Celular , Cristalografia por Raios X , Cimentos de Ionômeros de Vidro/síntese química , Teste de Materiais , Microscopia Eletrônica de Varredura , Mitocôndrias/efeitos dos fármacos , Ratos
13.
J Dent ; 34(8): 598-601, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16545900

RESUMO

Glass-ionomer cements (GIC) have been extensively used in dentistry for over 30 years. Due to their excellent biocompatibility in dental applications GIC have been formulated for medical applications. The past decade has seen some impressive advances in the development of medical GICs, however these advances have been matched by serious critical problems. This review examines the properties of GICs, which can influence their behaviour in a biological environment. The progress made and the problems encountered in the development of these bone cements will also be addressed. The review will conclude with the research currently being employed to optimise the biocompatibility of these important biomaterials. There is little doubt that GICs compare favourably with alternative bone cements for specific applications, based on in vitro and in vivo studies. There is however, a degree of risk inherent in the use of any medical device or biomaterial. GICs must therefore be used carefully and in accordance with the instructions that are based on a significant body of research data.


Assuntos
Cimentos Ósseos/toxicidade , Cimentos de Ionômeros de Vidro/toxicidade , Alumínio/toxicidade , Animais , Artroplastia , Regeneração Óssea/efeitos dos fármacos , Humanos , Teste de Materiais
14.
Transplant Proc ; 37(2): 937-9, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15848580

RESUMO

We looked at mycobacterial infections occurring after a kidney transplant to determine incidence, risk factors, and outcomes. Of 3921 kidney transplants performed between 1984 and 2002, 18 (0.45%) (10 men, eight women; 11 cadaveric donor, seven living donor graft) were identified as having mycobacterial infection at some time posttransplant. Mean age at transplant was 38.3 years. Racial background was: Caucasian (n = 12), African-American (n = 2), Native Indian (n = 2), Hispanic (n = 1), and Middle Eastern (n = 1). The majority had a kidney alone (n = 14). Four recipients had simultaneous transplant of a second organ: pancreas (n = 2), islets (n = 1), and liver (n = 1). None of the 18 recipients had documented mycobacterial infection pretransplant. One recipient had a positive Mantoux test at the time of transplant and then developed pulmonary tuberculosis 4 months posttransplant; the remaining 17 patients had either negative (n = 10) or unavailable (n = 7) pretransplant Mantoux results. Mean time to infection was 3.2 years (range 1 week to 12 years). The most common site of infection was respiratory (n = 8). Other sites included musculoskeletal (n = 4), skin (n = 3), gyn (n = 1), and other (n = 2). Only three of the infections were with mycobacterial tuberculi; the others were with avium (n = 5), chelonae (n = 2), or other nontuberculous mycobacteria. Risk factors included previous TB exposure, occupational exposure, or accidental soft tissue injury. Soft tissue infections often presented as chronic unhealed wounds and required extensive surgical debridements. With mean follow-up of 12.5 years since transplant and 9.2 years since infection, 13 of the recipients are alive and well; causes of death included cardiovascular (n = 3) and sepsis (n = 2).


Assuntos
Transplante de Rim/efeitos adversos , Infecções por Mycobacterium/epidemiologia , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Transplante das Ilhotas Pancreáticas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Infecções por Mycobacterium/classificação , Transplante de Pâncreas/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/microbiologia , Estudos Retrospectivos , Fatores de Risco
15.
Biomaterials ; 24(18): 3153-60, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12895588

RESUMO

The effects of devitrification of an ionomer glass with a molar composition 4.5SiO(2).3Al(2)O(3).1.5P(2)O(5).3CaO.2CaF(2) on cement formation and in vitro biocompatibility were investigated. Differential thermal analysis was used to study the phase evolution in the glass, and to determine the heat treatments for production of glass-ceramics. X-ray diffraction patterns from glass frit heat-treated at 750 degrees C for 2h contained peaks corresponding to apatite (JCPDS 15-876), whereas for samples heat-treated at 950 degrees C for 2h apatite and mullite (JCPDS 15-776) were the major phases detected. Transmission electron microscopy (TEM) confirmed that apatite and apatite-mullite phases were present after heat treatments at 750 degrees C and 950 degrees C respectively. Glass and glass-ceramics were ground to prepare <45microm powders and glass ionomer cements were produced using a ratio of 1g powder: 0.2g PAA: 0.3g 10% m/v tartaric acid solution in water. In vitro biocompatibility was evaluated using cultured rat osteosarcoma (ROS) cells. Scanning electron microscopy (SEM) showed that cells colonised the surfaces of cements prepared using untreated ionomer glass and glass crystallised to form apatite (750 degrees C/2h). However, quantitative evaluation using MTT and total protein assays indicated that more cell growth occurred in the presence of cements prepared using ionomer glasses crystallised to apatite than cements prepared using untreated glass. The least cell growth and respiratory activity was observed on cements made with crystallised glass containing both apatite and mullite. It was concluded that the controlled devitrification of ionomer glasses could be used to produce GIC bone cements with improved biocompatibility.


Assuntos
Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Cristalização/métodos , Cimentos de Ionômeros de Vidro/química , Cimentos de Ionômeros de Vidro/farmacologia , Temperatura Alta , Osteossarcoma/metabolismo , Osteossarcoma/ultraestrutura , Animais , Materiais Biocompatíveis/síntese química , Divisão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Cimentos de Ionômeros de Vidro/síntese química , Teste de Materiais , Conformação Molecular , Transição de Fase , Ratos
16.
Clin Transplant ; 16(6): 425-9, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12437622

RESUMO

BACKGROUND: We previously defined an intermediate group of cadaver kidney transplant recipients who do not have immediate graft function (IGF), but do not have sufficient graft dysfunction to be classified as having delayed graft function (DGF). We showed that this group with slow graft function (SGF) had an increased risk of rejection and inferior long-term results vs. recipients with IGF. The aim of our current study was to determine risk factors for SGF, which have not been well defined (in contrast to risk factors for DGF). METHODS: Between January 1, 1984 and September 30, 1999, we performed 896 adult cadaver kidney transplants at the University of Minnesota. Recipients were analysed in three groups based on initial graft function: IGF [creatinine (Cr) < 3 mg/dL by post-operative day (POD) no. 5], SGF (Cr > 3 mg/dL on POD no. 5, but no need for dialysis), and DGF (need for dialysis in the first week post-transplant). A multivariate analysis looked specifically at risk factors for SGF, as compared with risk factors for DGF. Outcomes with regard to graft survival and acute rejection (AR) rates were determined for the three groups. RESULTS: Of the 896 recipients, 425 had IGF, 238 had SGF, and 233 had DGF. A multivariate analysis of risk factors for SGF showed donor age >50 yr (RR=3.3, p=0.0001) and kidney preservation time >24 h (RR=1.6, p=0.01) to be the most significant risk factors. A multivariate analysis of risk factors for DGF showed similar findings, although high panel-reactive antibodies (PRA) and donor Cr >1.7 mg/dL were also significant risk factors for DGF. Initial function of the graft significantly influenced the subsequent risk of AR: at 12 months post-transplant, the incidence of AR was 28% for those with IGF, 38% for those with SGF, and 44% for those with DGF (p=0.04 for SGF vs. DGF). Initial graft function also significantly influenced graft survival: the 5-yr death-censored graft survival rate was 89% for recipients with IGF, 72% for those with SGF, and 67% for those with DGF (p=0.01 for IGF vs. SGF; p=0.03 for SGF vs. DGF). CONCLUSIONS: SGF represents part of the spectrum of graft injury and post-transplant graft dysfunction. Risk factors for SGF are similar to those seen for DGF. Even mild to moderate graft dysfunction post-transplant can have a negative impact on long-term graft survival.


Assuntos
Transplante de Rim , Feminino , Sobrevivência de Enxerto , Humanos , Transplante de Rim/imunologia , Transplante de Rim/fisiologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Período Pós-Operatório , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
17.
Ann Surg ; 234(2): 149-64, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11505060

RESUMO

OBJECTIVE: To review a single center's experience and outcome with living donor transplants. SUMMARY BACKGROUND DATA: Outcome after living donor transplants is better than after cadaver donor transplants. Since the inception of the authors' program, they have performed 2,540 living donor transplants. For the most recent cohort of recipients, improvements in patient care and immunosuppressive protocols have improved outcome. In this review, the authors analyzed outcome in relation to protocol. METHODS: The authors studied patient and graft survival by decade. For those transplanted in the 1990s, the impact of immunosuppressive protocol, donor source, diabetes, and preemptive transplantation was analyzed. The incidence of rejection, posttransplant steroid-related complications, and return to work was determined. Finally, multivariate analysis was used to study risk factors for worse 1-year graft survival and, for those with graft function at 1 year, to study risk factors for worse long-term survival. RESULTS: For each decade since 1960, outcome has improved after living donor transplants. Compared with patients transplanted in the 1960s, those transplanted in the 1990s have better 8-year actuarial patient and graft survival rates. Death with function and chronic rejection have continued to be a major cause of graft loss, whereas acute rejection has become a rare cause of graft loss. Cardiovascular deaths have become a more predominant cause of patient death; infection has decreased. Donor source (e.g., ideally HLA-identical sibling) continues to be important. For living donor transplants, rejection and graft survival rates are related to donor source. The authors show that patients who had preemptive transplants or less than 1 year of dialysis have better 5-year graft survival and more frequently return to full-time employment. Readmission and complications remain problems; of patients transplanted in the 1990s, only 36% never required readmission. Similarly, steroid-related complications remain common. The authors' multivariate analysis shows that the major risk factor for worse 1-year graft survival was delayed graft function. For recipients with 1-year graft survival, risk factors for worse long-term outcome were pretransplant smoking, pretransplant peripheral vascular disease, pretransplant dialysis for more than 1 year, one or more acute rejection episodes, and donor age older than 55. CONCLUSIONS: These data show that the outcome of living donor transplants has continued to improve. However, for living donors, donor source affects outcome. The authors also identify other major risk factors affecting both short- and long-term outcome.


Assuntos
Rejeição de Enxerto/etiologia , Nefropatias/cirurgia , Transplante de Rim , Doadores Vivos , Complicações Pós-Operatórias/etiologia , Adolescente , Adulto , Cadáver , Criança , Pré-Escolar , Estudos de Coortes , Quimioterapia Combinada , Feminino , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/mortalidade , Sobrevivência de Enxerto , Teste de Histocompatibilidade , Humanos , Imunossupressores/administração & dosagem , Nefropatias/mortalidade , Transplante de Rim/imunologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/mortalidade , Fatores de Risco , Análise de Sobrevida , Resultado do Tratamento
18.
Clin Transplant ; 15(3): 154-8, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11389704

RESUMO

BACKGROUND: Renal transplant recipients are known to be at increased risk for developing cardiac disease. In both general and peripheral vascular surgery, pre-operative risk stratification (and intervention when indicated) has decreased the incidence of peri-operative cardiac complications. In this study, we set out to identify subsets of patients at high risk for peri-operative cardiac complications after a renal transplant. METHODS: We retrospectively reviewed the records of 2694 adult renal transplants performed at the University of Minnesota between January 1, 1985 and December 31, 1998. We determined the incidence of peri-operative (within 30 d post-transplant) cardiac complications, including myocardial infarction (MI). Risk factors for the development of these complications were determined by multivariate analysis. RESULTS: We found 163 peri-operative cardiac complications, for an overall incidence of 6.1%. Specific cardiac complications included MI (n=43, 1.6%), arrhythmia (n=74, 2.7%), angina (n=31, 1.2%), cardiac arrest (n=13, 0.5%), and congestive heart failure (n= 2, 0.1%). By multivariate analysis, significant risk factors for any cardiac complication were age> or =50 yr (relative risk (RR)=3.0, p=0.0001) and pre-transplant cardiac disease (RR=3.3, p=0.0001). Not significant were diabetes mellitus (DM), cadaver donor source, pre-transplant dialysis, a history of smoking, and hypertension. Significant risk factors for peri-operative MI were age> or =50 yr, pre-existing cardiac disease, and DM. Diabetic patients with pre-existing cardiac disease were at especially high risk for peri-operative cardiac events. CONCLUSIONS: Patients>50 yr and those with pre-existing cardiac disease, especially if diabetic, are at significantly increased risk for developing peri-operative cardiac complications after a renal transplant. Such patients require aggressive pre-operative investigations, which may include coronary angiography, to decrease the risk of post-transplant complications.


Assuntos
Doenças Cardiovasculares/epidemiologia , Transplante de Rim , Complicações Pós-Operatórias/epidemiologia , Adulto , Fatores Etários , Feminino , Humanos , Incidência , Masculino , Morbidade , Análise Multivariada , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Procedimentos Cirúrgicos Vasculares
20.
Am J Transplant ; 1(3): 278-83, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12102262

RESUMO

UNLABELLED: Steroids are associated with significant postoperative complications (hypertension, cosmetic changes, bone loss, hyperlipidemia, diabetes, and cataracts). Most develop early; in addition, late post-transplant steroid withdrawal in kidney transplant recipients has been associated with increased acute rejection (AR). To obviate these problems, we studied outcome of a protocol of rapid discontinuation of prednisone (RDS) (steroids stopped on POD6). Between November 1, 1999 and October 31, 2000, 51 adult living donor (LD) first transplant recipients (2 HLA-id, 28 non-id relative, 21 LURD) were immunosuppressed with thymoglobulin (1.25 mg/kg intraoperatively and then qdx4); prednisone (P) (500 mg methylprednisolone intraoperatively, 1 mg/kg x 1 day, 0.5 mg/kg x 2 days, 0.25 mg/kg x 2 days, then d/c); MMF, 1 g b.i.d.; and CSA, 4 mg/kg b.i.d. adjusted to achieve levels of 150-200 ng/mL (by HPLC). Exclusion criteria were delayed graft function or primary disease requiring P. Minimum follow-up was 5.5 months (range 5.5 to 17.5 months). Outcome was compared vs. previous cohorts of LD recipients immunosuppressed with P/AZA/CSA (n = 171) or P/MMF/CSA (n = 43) (both without antibody induction). RESULTS: For the RDS group, average CSA level (+/- S.E.) at 3 and 6 months was 190 +/- 12 and 180 +/- 9; avg. MMF dose, 1.7 +/- 0.1 g and 1.7 +/- 0.1 g. There was no significant difference in 6- and 12-month actuarial patient survival, graft survival and rejection-free graft survival between recipients on the RDS protocol vs. historical controls. For RDS recipients, actuarial 6- and 12-month rejection-free graft survival was 87%. Of the 51 RDS recipients, five (10%) have had AR (at 20 days, 1 month, 3 months, 3 months, and 3.5 months post-transplant). After treatment, all five were maintained on 5 mg P; there have been no second AR episodes. Two additional recipients were started on 5 mg P due to low white blood count (WBC) and low/no MMF. Of the 51 grafts, one has failed (death with function). Average serum Cr level (+/- S.E.) at 3 and 6 months for RDS recipients was 1.7 +/- 0.5 (NS vs. historical controls). CONCLUSION: For low-risk LD recipients, a kidney transplant with an RDS protocol does not increase risk of AR or graft loss. Future studies will need to be done to assess AR rates with an RDS protocol in cadaver transplant recipients and in recipients with delayed graft function.


Assuntos
Imunossupressores/administração & dosagem , Transplante de Rim/imunologia , Doadores Vivos , Ácido Micofenólico/análogos & derivados , Prednisona/uso terapêutico , Esteroides/uso terapêutico , Azatioprina/uso terapêutico , Esquema de Medicação , Quimioterapia Combinada , Humanos , Ácido Micofenólico/uso terapêutico , Núcleo Familiar , Projetos Piloto , Complicações Pós-Operatórias/induzido quimicamente , Complicações Pós-Operatórias/prevenção & controle , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Esteroides/administração & dosagem , Esteroides/efeitos adversos , Fatores de Tempo
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