RESUMO
Apolipoprotein L1 gene (APOL1) nephropathy variants in African American deceased kidney donors were associated with shorter renal allograft survival in a prior single-center report. APOL1 G1 and G2 variants were genotyped in newly accrued DNA samples from African American deceased donors of kidneys recovered and/or transplanted in Alabama and North Carolina. APOL1 genotypes and allograft outcomes in subsequent transplants from 55 U.S. centers were linked, adjusting for age, sex and race/ethnicity of recipients, HLA match, cold ischemia time, panel reactive antibody levels, and donor type. For 221 transplantations from kidneys recovered in Alabama, there was a statistical trend toward shorter allograft survival in recipients of two-APOL1-nephropathy-variant kidneys (hazard ratio [HR] 2.71; p = 0.06). For all 675 kidneys transplanted from donors at both centers, APOL1 genotype (HR 2.26; p = 0.001) and African American recipient race/ethnicity (HR 1.60; p = 0.03) were associated with allograft failure. Kidneys from African American deceased donors with two APOL1 nephropathy variants reproducibly associate with higher risk for allograft failure after transplantation. These findings warrant consideration of rapidly genotyping deceased African American kidney donors for APOL1 risk variants at organ recovery and incorporation of results into allocation and informed-consent processes.
Assuntos
Apolipoproteínas/genética , Negro ou Afro-Americano/genética , Variação Genética/genética , Rejeição de Enxerto/genética , Nefropatias/cirurgia , Transplante de Rim , Lipoproteínas HDL/genética , Doadores de Tecidos , Adolescente , Adulto , Alabama , Aloenxertos , Apolipoproteína L1 , Feminino , Genótipo , Rejeição de Enxerto/etnologia , Rejeição de Enxerto/mortalidade , Humanos , Nefropatias/mortalidade , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , North Carolina , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
Coding variants in the apolipoprotein L1 gene (APOL1) are strongly associated with nephropathy in African Americans (AAs). The effect of transplanting kidneys from AA donors with two APOL1 nephropathy risk variants is unknown. APOL1 risk variants were genotyped in 106 AA deceased organ donors and graft survival assessed in 136 resultant kidney transplants. Cox-proportional hazard models tested for association between time to graft failure and donor APOL1 genotypes. The mean follow-up was 26.4 ± 21.8 months. Twenty-two of 136 transplanted kidneys (16%) were from donors with two APOL1 nephropathy risk variants. Twenty-five grafts failed; eight (32%) had two APOL1 risk variants. A multivariate model accounting for donor APOL1 genotype, overall African ancestry, expanded criteria donation, recipient age and gender, HLA mismatch, CIT and PRA revealed that graft survival was significantly shorter in donor kidneys with two APOL1 risk variants (hazard ratio [HR] 3.84; p = 0.008) and higher HLA mismatch (HR 1.52; p = 0.03), but not for overall African ancestry excluding APOL1. Kidneys from AA deceased donors harboring two APOL1 risk variants failed more rapidly after renal transplantation than those with zero or one risk variants. If replicated, APOL1 genotyping could improve the donor selection process and maximize long-term renal allograft survival.
Assuntos
Apolipoproteínas/genética , Transplante de Rim/métodos , Lipoproteínas HDL/genética , Insuficiência Renal/etnologia , Insuficiência Renal/terapia , Adulto , Negro ou Afro-Americano , Apolipoproteína L1 , Feminino , Seguimentos , Genótipo , Glomerulosclerose Segmentar e Focal/imunologia , Sobrevivência de Enxerto , Antígenos HLA/imunologia , Humanos , Imunossupressores/uso terapêutico , Rim/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Risco , Doadores de Tecidos , Transplante HomólogoRESUMO
PURPOSE: The purpose of the study was to characterize differences in donor and recipient relationships between African American (AA) and Caucasian living kidney donors. METHODS: Data from all successful living kidney donors at a single institution between 1991 and 2009 were reviewed. Relationships between donor and recipient were categorized and between-group comparisons performed. RESULTS: The study sample consisted of 73 (18%) AA and 324 Caucasian living kidney donors. The distribution of donor-recipient relationships differed significantly between AA and Caucasians. AA donors were more likely to be related to the recipient (88% vs. 74%, p = 0.007) than Caucasians. AA donors were more likely to participate in child to parent donation and were less likely to participate in parent to child donation or to donate to unrelated individuals. Sibling and spousal donations were similar in both groups. Caucasian donors were more likely to be unrelated to the recipient than AA donors. CONCLUSIONS: Differences exist in donor-recipient relationships between AA and Caucasian living kidney donors. Future studies exploring cultural differences and family dynamics may provide targeted recruitment strategies for AA and Caucasian living kidney donors. Living unrelated kidney transplantation appears to be a potential growth area for living kidney donation in AA.
Assuntos
Negro ou Afro-Americano/estatística & dados numéricos , Transplante de Rim/psicologia , Doadores Vivos/estatística & dados numéricos , População Branca/estatística & dados numéricos , Adulto , Atitude Frente a Saúde , Criança , Família , Feminino , Humanos , Doadores Vivos/psicologia , Masculino , Pais , Estudos Retrospectivos , CônjugesRESUMO
OBJECTIVE: To determine the clinical characteristics, short-term outcome and future athletic performance of foals with septic osteomyelitis. DESIGN: Retrospective clinical study of 108 Thoroughbred foals with radiographic evidence of bone infection that were presented at the Scone Veterinary Hospital between August 1995 and December 2001. Medical records were reviewed and information concerning signalment, the clinical, laboratory and radiographic findings, treatment and outcome was obtained. Racing records were obtained and evaluated for surviving foals that had reached racing age. RESULTS: Mean age of foals at initial evaluation was 39 days (range 1-180 days); 21 foals had multiple radiographic bone lesions (19.4%), and 76 had concurrent septic arthritis (70.4%). The most frequently affected bones were the femur, tibia and distal phalanx. In total, 87 foals were discharged from the hospital (80.6%), 79 survived long-term to reach racing age and 52 raced (65.8%). Overall, 48% (52/108) of the foals treated for osteomyelitis raced. Foals less than 30 days of age at the time of diagnosis, critically ill foals and those with multiple bones or joints affected were significantly less likely to be discharged from hospital. Multiple septic joints, but not multiple bone involvement, had an unfavourable prognosis for racing. CONCLUSIONS: The prognosis for survival of foals with septic osteomyelitis or osteitis is favourable. Multiple bone or joint involvement is an important short-term prognostic indicator; however, the involvement of multiple joints, but not multiple infected bones, is associated with an unfavourable prognosis for racing.
Assuntos
Artrite Infecciosa/veterinária , Doenças dos Cavalos/fisiopatologia , Osteomielite/veterinária , Condicionamento Físico Animal , Esportes/estatística & dados numéricos , Idade de Início , Animais , Animais Recém-Nascidos , Artrite Infecciosa/diagnóstico por imagem , Artrite Infecciosa/patologia , Artrite Infecciosa/fisiopatologia , Feminino , Doenças dos Cavalos/diagnóstico por imagem , Doenças dos Cavalos/patologia , Cavalos , Masculino , Osteomielite/diagnóstico por imagem , Osteomielite/patologia , Osteomielite/fisiopatologia , Prognóstico , Radiografia , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
INTRODUCTION: Although African Americans (AA) are considered higher risk kidney donors than Caucasians, limited data are available regarding outcomes of AA donors. METHODS: We performed a single-center retrospective review of all kidney donors from 1993 to 2007 and evaluated race/ethnic differences in post-donation changes in renal function, incident proteinuria, and systolic blood pressure (SBP) using linear mixed models. RESULTS: A total of 336 kidney donors (63 AA, 263 Caucasian, 10 other) were evaluated. Before donation, AA had higher serum creatinine concentrations, estimated glomerular filtration rate (GFR) values, and SBP levels than Caucasians. No significant changes in SBP or renal function were observed between the two groups within the first year after donation, although results were limited by incomplete follow-up. CONCLUSION: AA had higher pre-donation serum creatinine, GFR, and SBP values compared to Caucasians; however, the degree of change in renal function and blood pressure did not differ between groups following kidney donation. Although long-term studies are needed, our study suggests that AA and Caucasians experience similar short-term consequences after donation. The incomplete data available on donor outcomes in our center and in prior publications also indicates a global need to implement systems for structured follow-up of live kidney donors.
Assuntos
Negro ou Afro-Americano/estatística & dados numéricos , Sobrevivência de Enxerto , Transplante de Rim , Rim/fisiologia , Doadores Vivos , População Branca/estatística & dados numéricos , Adulto , Pressão Sanguínea , Creatinina/sangue , Feminino , Taxa de Filtração Glomerular , Humanos , Testes de Função Renal , Masculino , Prognóstico , Proteinúria/diagnóstico , Estudos Retrospectivos , Fatores de TempoRESUMO
OBJECTIVE: The ENDURANCE study evaluated the efficacy of vardenafil, a phosphodiesterase type 5 (PDE5) inhibitor, in men with erectile dysfunction (ED), by measuring the duration of erection leading to successful intercourse using a stopwatch as the assessment instrument. METHODS: This was a randomised, multicentre, double-blind, placebo-controlled, crossover study consisting of a 4-week treatment-free run-in phase after which patients were randomised to either fixed-dose vardenafil 10 mg or placebo (to be administered 60 min prior to intercourse) and entered the first of the two 4-week double-blind treatment periods, separated by a 1-week washout. The primary efficacy end-point was the stopwatch-assessed duration of erection, which was defined as the time from erection perceived hard enough for penetration until withdrawal from the partner's vagina leading to successful intercourse as measured by Sexual Encounter Profile Question 3 (SEP-3). Secondary efficacy end-points included SEP-2 and SEP-3 success rates, the erectile function domain of the International Index of Erectile Function, global assessment questionnaire, change from baseline in duration of erection and duration of erection not leading to successful intercourse. Safety was assessed by adverse events (AEs), laboratory samples, vital signs and ECGs. RESULTS: Of the 191 men included in the safety population, 40% had moderate ED and 33% had severe ED at baseline. The duration of erection (least squares mean +/- SE) leading to successful intercourse was longer with vardenafil than with placebo (12.81 +/- 1.00 min vs. 5.45 +/- 1.00 min; p < 0.001). The differences recorded for all secondary end-points were statistically significant in favour of vardenafil compared with placebo (p < 0.001), with the exception of duration of erection not leading to successful intercourse. Vardenafil was well tolerated in this study; the majority of AEs being mild-to-moderate in intensity. CONCLUSION: Vardenafil 10-mg therapy provided a statistically superior duration of erection leading to successful intercourse in men with ED compared with placebo.
Assuntos
Coito , Disfunção Erétil/tratamento farmacológico , Imidazóis/uso terapêutico , Ereção Peniana/efeitos dos fármacos , Inibidores de Fosfodiesterase/uso terapêutico , Piperazinas/uso terapêutico , Adulto , Estudos Cross-Over , Método Duplo-Cego , Humanos , Imidazóis/efeitos adversos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Inibidores de Fosfodiesterase/efeitos adversos , Piperazinas/efeitos adversos , Índice de Gravidade de Doença , Sulfonas/efeitos adversos , Sulfonas/uso terapêutico , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento , Triazinas/efeitos adversos , Triazinas/uso terapêutico , Dicloridrato de Vardenafila , Adulto JovemRESUMO
A series of abortions occurred in mares in New South Wales during 2004 that involved similar and unusual findings on post mortem examination of aborted fetuses and fetal membranes. The term Equine Amnionitis and Fetal Loss (EAFL) was developed to describe the condition. This form of abortion had not been previously recognised in Australia. The pathology alone is not specific for EAFL and diagnosis requires demonstration of a combination of certain pathological and bacteriological features. The purpose of this paper is to describe patterns considered consistent with EAFL cases as a working case definition for use by veterinarians and veterinary pathologists in identifying future cases of EAFL. More detailed papers are in preparation to fully describe the epidemiological, histopathological, and microbiological aspects of EAFL.
Assuntos
Aborto Animal/etiologia , Corioamnionite/veterinária , Doenças dos Cavalos/diagnóstico , Feto Abortado/microbiologia , Feto Abortado/patologia , Aborto Animal/microbiologia , Animais , Corioamnionite/diagnóstico , Corioamnionite/microbiologia , Corioamnionite/patologia , Diagnóstico Diferencial , Membranas Extraembrionárias/microbiologia , Membranas Extraembrionárias/patologia , Feminino , Doenças dos Cavalos/microbiologia , Doenças dos Cavalos/patologia , Cavalos , GravidezRESUMO
BACKGROUND: African Americans (AA) and women are less likely to receive a live kidney donor (LKD) transplant than Caucasians or men. Reasons for non-donation are poorly understood. METHODS: A retrospective review of 541 unsuccessful LKD was performed to explore reasons for non-donation and to assess for racial and/or gender differences. RESULTS: We identified 138 AA and 385 Caucasian subjects who volunteered but did not successfully donate. Females (58.2%) were more likely to be excluded than males due to reduced renal function (glomerular filtration rate < 85 mL/min, 7.9% vs. 0.9%, p < 0.0001) or failure to complete the evaluation (6.4% vs. 1.8%, p = 0.01). AA were more commonly excluded due to obesity (body mass index >or= 32 kg/m(2); 30.4% AA vs. 16.6% Caucasian, p = 0.0005) or failure to complete the evaluation (12.3% AA vs. 1.8% Caucasian, p < 0.0001) whereas Caucasians were more often excluded due to kidney stones (1.5% AA vs. 7.3% Caucasian, p = 0.01). CONCLUSIONS: Significantly different reasons for exclusion of LKD exist between potential Caucasian and AA LKD, particularly among women. Among the differences that we observed are potentially modifiable barriers to donation including obesity and failure to complete the donor evaluation. A further understanding of these barriers may help point to strategies for more effective recruitment and successful LKD.
Assuntos
População Negra/estatística & dados numéricos , Transplante de Rim/estatística & dados numéricos , Doadores Vivos/psicologia , População Branca/estatística & dados numéricos , Adulto , Atitude Frente a Saúde , Feminino , Taxa de Filtração Glomerular , Humanos , Testes de Função Renal , Masculino , Estudos Retrospectivos , Fatores de Risco , Fatores SexuaisRESUMO
OBJECTIVE: Limited data are available on extended (EX) donor criteria in pancreatic transplantation (PTX). METHODS: This retrospective study from February 2007 through April 2007 compared 2 cohorts of simultaneous kidney-pancreas transplantations (SKPT): the first from EX donors, which were defined as age <10 years or > or =45 years, or donation after cardiac death [DCD]), and the second from conventional (CONV) donors. RESULTS: Among 79 SKPT, 19 (24%) were from EX donors (12 older than age 45 [mean age, 50.2 years], 3 pediatric donors <10, and 4 DCD donors) and the remaining 60 SKPT from CONV donors. The mean donor age was higher in EX than CONV donors (38 vs 25 years, P < .05). There were no other differences between the 2 cohorts. With a similar median follow-up of 29 months, patient, kidney and pancreatic graft survival rates were 89%, 89%, and 79%, for the EX, whereas corresponding outcomes for CONV donors were 93%, 87%, and 80%, respectively (all P = NS). The incidences were similar for delayed kidney graft function (5% in each group), early pancreatic graft loss due to thrombosis (5% EX vs 8% CONV donors), acute rejection (16% EX vs 18% CONV donors), surgical complications, and infections. There were no significant differences in 1-year mean serum creatinine (1.4 mg/dL in each group) or glycohemoglobin (5.2% vs 5.5%) levels between the EX and CONV donor groups, respectively. CONCLUSION: Short-term outcomes among SKPT from selected EX donors were comparable to CONV donors. Donors at the extremes of age and DCD donors may represent underused resources in SKPT.
Assuntos
Transplante de Rim , Transplante de Pâncreas/métodos , Sistema Porta , Doadores de Tecidos , Adolescente , Adulto , Criança , Estudos de Coortes , Morte , Drenagem/métodos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Listas de EsperaRESUMO
OBJECTIVE: The objective of this study was to review the incidence, risk factors, and impact of bacteremia after pancreas transplantation (PTX). METHODS: We performed a retrospective analysis of consecutive simultaneous kidney-pancreas transplantations (SKPTs) and solitary PTXs from January 2002 through April 2007. Positive blood cultures were correlated with other coexisting infections and parameters. RESULTS: One hundred ten PTXs with enteric drainage included 80 SKPTs and 30 solitary PTXs. Mean follow-up was 32 months. Bacteremia occurred in 29 (26%) patients with 5 (17%) being recurrent; it was seen during the first month after transplantation in 13 (12%), between 1 and 3 months in 12 (11%), between 3 and 12 months in 3 (3%), and after the first year in 3 cases (3%). Typical organisms were as follows: MRSE, MSSE, Klebsiella, Escherichia coli, vancomycin-resistant enterococci (VRE), and Acinetobacteri. Bacteremia was associated with coexisting site infection in 20 cases (69%): deep abdominal wound (31%); line (31%); urinary tract (34%); and pulmonary (7%). Similar bacterial species in blood and a coexisting site occurred in 15 cases (52%). No correlation was seen with cytomegalovirus (CMV) infections. In the first year, bacteremia was associated with more acute rejection episodes (32% vs 17%; P = .09), surgical complications (54% vs 42%; P = .267), mortality (11% vs 4%; P = .15), and death-censored pancreatic (14% vs 9%; P = .39) and kidney (4% vs 0; P = .08) graft loss. Fewer patients with bacteremia received alemtuzumab compared with rATG induction (14% vs 39%; P = .04). CONCLUSIONS: Bacteremias were common within 3 months of PTX. A significant number (39%) were multidrug resistant. The majority were accompanied by abdominal, urinary, or line infections. Bacteremias were associated with slightly higher incidences of rejection, mortality, and graft loss.
Assuntos
Bacteriemia/epidemiologia , Drenagem/efeitos adversos , Transplante de Rim/efeitos adversos , Transplante de Pâncreas/efeitos adversos , Adulto , Bacteriemia/etiologia , Bactérias/classificação , Bactérias/isolamento & purificação , Humanos , Imunossupressores/uso terapêutico , Incidência , Transplante de Rim/imunologia , Transplante de Rim/mortalidade , Transplante de Pâncreas/imunologia , Transplante de Pâncreas/mortalidade , Sistema Porta , Estudos Retrospectivos , Análise de Sobrevida , SobreviventesRESUMO
OBJECTIVE: To analyze outcomes in simultaneous kidney-pancreas transplantation (SKPT) recipients who retain C-peptide production at the time of SKPT. METHODS: This retrospective analysis of SKPTs from January 2002 through January 2007 compared outcomes between patients with absent or low C-peptide levels (<2.0 ng/mL, group A) with those having levels > or =2.0 ng/mL (group B). RESULTS: Among 74 SKPTs, 67 were in group A and seven in group B (mean C-peptide level 5.7 ng/mL). During transplantation, group B subjects were older (mean age 51 vs 41 years, P = .006); showed a later age of onset of diabetes (median 35 vs 13 years, P = .0001); weighed more (median 77 vs 66 kg, P = .24); had a greater proportion of African-Americans (57% vs 13%, P = .004); and had a longer pretransplant duration of dialysis (median 40 vs 14 months, P = .14). With similar median follow-up of 40 months, death-censored kidney (95% group A vs 100% group B, P = NS) and pancreas (87% group A vs 100% group B, P = NS) graft survival rates were similar, but patient survival (94% group A vs 71% group B, P = .03) was greater in group A. At 1-year follow-up, there were no significant differences in rejection episodes, surgical complications, infections, readmissions, hemoglobin A1C or C-peptide levels, serum creatinine, or MDRD GFR levels. CONCLUSIONS: Diabetic patients with measurable C-peptide levels before transplant were older, overweight, more frequently African-American and had a later age of onset of diabetes, longer duration of pretransplant dialysis, and reduced patient survival compared to insulinopenic patients undergoing SKPT. The other outcomes were similar.
Assuntos
Peptídeo C/sangue , Diabetes Mellitus Tipo 2/cirurgia , Transplante de Rim/fisiologia , Transplante de Pâncreas/fisiologia , Cuidados Pré-Operatórios , Adulto , Idade de Início , Diabetes Mellitus Tipo 1/cirurgia , Nefropatias Diabéticas/cirurgia , Teste de Histocompatibilidade , Humanos , Transplante de Rim/imunologia , Pessoa de Meia-Idade , Transplante de Pâncreas/imunologia , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Listas de EsperaRESUMO
UNLABELLED: The purpose of this study was to retrospectively review our experience with "extreme" pancreas donors compared to conventional (CONV) donors. METHODS: "Extreme" (EX) pancreas donors were defined as deceased donors (DDs) age >50 years, <8 years, donation after cardiac death (DCD), and targeted for organ discard. RESULTS: From January 2002 through January 2005, we performed 40 simultaneous kidney-pancreas transplants (SKPT) with Thymoglobulin induction, including 9 (22.5%) from EX and 31 from CONV DDs. Mean DD age was higher in EX DD (41.2 years EX vs 26.0 CONV, P < .05), but mean recipient age and cold ischemia times did not differ between groups. With a mean follow-up of 16.8 months in the EX DD group, patient and kidney graft survival rates are both 100%, and the pancreas graft survival rate is 89%. With a mean follow-up of 21.7 months in the CONV DD group, patient and kidney graft survival rates are both 93.5% and the pancreas graft survival rate is 77.4%. All patients with surviving grafts exhibited good initial (1 case of delayed kidney graft function in a CONV DD) and stable long-term kidney and pancreas graft function. Mean length of initial hospital stay and the incidences of acute rejection, readmissions, operative complications, and infections were similar between groups. CONCLUSIONS: The results of this study suggest that the limits of donor acceptability continue to evolve as excellent outcomes can be achieved in SKPTs from selected EX DDs.
Assuntos
Soro Antilinfocitário/uso terapêutico , Transplante de Rim/fisiologia , Transplante de Pâncreas/fisiologia , Doadores de Tecidos/estatística & dados numéricos , Adolescente , Adulto , Fatores Etários , Criança , Rejeição de Enxerto/epidemiologia , Sobrevivência de Enxerto , Cardiopatias/mortalidade , Humanos , Imunossupressores/uso terapêutico , Transplante de Rim/imunologia , Pessoa de Meia-Idade , Transplante de Pâncreas/imunologia , Complicações Pós-Operatórias/epidemiologia , Resultado do TratamentoRESUMO
The purpose of this study was to retrospectively review outcomes in patients undergoing pancreas transplantation (PTX) with a novel induction protocol of alternate-day thymoglobulin (rATG) in combination with tacrolimus (TAC), mycophenolate mofetil (MMF), and steroids. From January 2002 through January 2005, we performed 55 PTXs in 53 patients. The first dose of rATG (1.5 mg/kg) was given intraoperatively, and subsequent doses were given on alternate days until therapeutic TAC levels (>8 ng/mL) were achieved. All patients underwent PTX with enteric drainage, including 51 with portal and 4 with systemic venous drainage. Patients received a minimum of 2 and maximum of 6 doses of rATG induction (median 3 doses). The patient group had a mean age of 42.8 years and included 40 simultaneous kidney-PTX, 11 sequential PTX after kidney, and 4 PTX-alone transplant recipients. Patient, kidney, and pancreas graft survival rates are 96%, 96%, and 84%, respectively, with a mean follow-up of 21 months. The incidence of acute rejection was 18%; there were no graft losses due to isolated acute rejection. The incidence of infection was 60%, but there were no cases of polyomavirus or Epstein-Barr virus infection and only 6 cases (11%) of cytomegalovirus infection. The composite endpoint of no rejection, graft loss, or mortality was attained by 71% of patients. At present, 94% of surviving patients are both dialysis and insulin-free, including 5 successful PTX retransplants. These findings suggest that PTX with portal-enteric drainage and alternate day rATG induction may result in excellent intermediate-term outcomes.
Assuntos
Soro Antilinfocitário/uso terapêutico , Imunossupressores/uso terapêutico , Transplante de Pâncreas/imunologia , Transplante de Pâncreas/métodos , Adulto , Soro Antilinfocitário/administração & dosagem , Drenagem , Esquema de Medicação , Sobrevivência de Enxerto , Humanos , Imunossupressores/administração & dosagem , Transplante de Pâncreas/mortalidade , Sistema Porta , Estudos Retrospectivos , Análise de SobrevidaRESUMO
The purpose of this study is to better characterize graft and patient survival posttransplantation by examining survival according to underlying renal disease for all first-time renal allograft recipients in the United Network for Organ Sharing (UNOS) registry. From 1987 through 1996, the UNOS registry collected data on 23,838 living and 67,183 cadaveric renal transplantations. This investigation included all patients undergoing their first renal transplantation for whom the underlying cause of renal failure could be identified and categorized. Gross 1- and 3-year patient and graft survival according to underlying renal disease are included. In addition, a Cox proportional hazards model was created to analyze the effect of underlying disease on graft and patient survival after adjusting for comorbid conditions, demographics, and type of renal transplant (living versus cadaveric). The association between underlying disease and graft and patient survival is shown. Amyloidosis, sickle cell anemia, scleroderma, and radiation nephritis are associated with poor graft and patient survival. The risk ratio for patient mortality was more than twice that for immunoglobulin A nephropathy for a number of conditions, including analgesic nephropathy, amyloidosis, and both forms of diabetes mellitus.
Assuntos
Nefropatias/patologia , Transplante de Rim , Sobrevivência de Enxerto , Humanos , Modelos de Riscos Proporcionais , Sistema de Registros/estatística & dados numéricos , Análise de Sobrevida , Fatores de TempoRESUMO
Tick histamine-binding proteins (HBPs) are lipocalins with two binding pockets. One of these binds histamine with a high affinity and is found at the position expected from other lipocalins, adjacent to the omega-loop at the open-end of the beta-barrel. A second binding cavity, which is a low-affinity site for histamine in one of the HBPs, is located at the end of the barrel that is closed off in other lipocalins. In order to create the second site, the 'closed-end' region has undergone a major reconstruction. Typical lipocalin characteristics, such as the 3(10) helix and a structural cluster of highly conserved residues, have been lost, while an alpha-helix now shields the cavity from the exterior. The prominence of acidic residues in the binding pockets is another distinctive characteristic of HBPs. Whereas most lipocalins have highly hydrophobic binding cavities designed to bind lipophilic compounds, HBPs have evolved to trap cationic, hydrophilic molecules.
Assuntos
Receptores Histamínicos H1/química , Receptores Histamínicos H2/química , Sequência de Aminoácidos , Animais , Sítios de Ligação , Cisteína/metabolismo , Histamina/metabolismo , Modelos Moleculares , Dados de Sequência Molecular , Estrutura Terciária de Proteína , Receptores Histamínicos H1/metabolismo , Receptores Histamínicos H2/metabolismo , Homologia de Sequência de Aminoácidos , Carrapatos , Triptofano/metabolismoRESUMO
OBJECTIVE: To identify factors affecting the prognosis for survival and athletic use in foals with septic arthritis. DESIGN: Retrospective study. ANIMALS: 93 foals with septic arthritis. PROCEDURE: Medical records were reviewed to obtain clinical findings, laboratory test results, radiographic findings, treatment method, and outcome. Race records for Thoroughbreds and Standardbreds were evaluated to determine whether foals subsequently raced and whether they raced successfully. RESULTS: 43 foals had 1 affected joint, 44 foals had multiple affected joints, and number of affected joints was not recorded for 6 foals. The femoropatellar and tarsocrural joints were most commonly affected. Osteomyelitis or degenerative joint disease were detected in 59% (46/78) of foals. Failure of passive transfer, pneumonia, and enteritis were common. Foals were treated with lavage, lavage and intra-articular administration of antibiotics, lavage and arthroscopic debridement with or without partial synovectomy, or lavage and arthrotomy to debride infected bone and systemic administration of antibiotics. Seventy-three foals survived to be discharged from hospital, and approximately a third raced. Isolation of Salmonella spp from synovial fluid was associated with an unfavorable prognosis for survival and multisystem disease was associated with an unfavorable prognosis for survival and ability to race; other variables were not significantly associated with survival and ability to race. CONCLUSIONS AND CLINICAL RELEVANCE: With treatment, the prognosis for survival of foals with septic arthritis was favorable, whereas prognosis for ability to race was unfavorable. Multisystem disease, isolation of Salmonella spp from synovial fluid, involvement of multiple joints, and synovial fluid neutrophil count > or = 95% at admission may be of prognostic value.
Assuntos
Artrite Infecciosa/veterinária , Doenças dos Cavalos/mortalidade , Condicionamento Físico Animal , Animais , Animais Recém-Nascidos , Artrite Infecciosa/mortalidade , Intervalos de Confiança , Feminino , Cavalos , Modelos Logísticos , Masculino , Razão de Chances , Prognóstico , Registros/veterinária , Estudos Retrospectivos , Esportes , Líquido Sinovial/citologia , Líquido Sinovial/microbiologiaRESUMO
High-affinity histamine-binding proteins (HBPs) were discovered in the saliva of Rhipicephalus appendiculatus ticks. Their ability to outcompete histamine receptors indicates that they suppress inflammation during blood feeding. The crystal structure of a histamine-bound HBP, determined at 1.25 A resolution, reveals a lipocalin fold novel in containing two binding sites for the same ligand. The sites are orthogonally arranged and highly rigid and form an internal surface of unusual polar character that complements the physicochemical properties of histamine. As soluble receptors of histamine, HBPs offer a new strategy for controlling histamine-based diseases.
Assuntos
Histamina/metabolismo , Receptores Histamínicos , Animais , Sítios de Ligação/fisiologia , Proteínas de Transporte/química , Clonagem Molecular , Cristalografia , Inibidores de Cisteína Proteinase/química , Feminino , Expressão Gênica/fisiologia , Hemeproteínas/química , Antagonistas dos Receptores Histamínicos/química , Proteínas de Insetos/química , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Lipocalina 1 , Masculino , Dados de Sequência Molecular , Inibidores da Agregação Plaquetária/química , Inibidores da Agregação Plaquetária/metabolismo , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Proteínas/química , Proteínas/genética , RNA Mensageiro/análise , Receptores Histamínicos/química , Receptores Histamínicos/genética , Receptores Histamínicos/metabolismo , Receptores Histamínicos H1/química , Receptores Histamínicos H1/genética , Receptores Histamínicos H1/metabolismo , Receptores Histamínicos H2/química , Receptores Histamínicos H2/genética , Receptores Histamínicos H2/metabolismo , Receptores Histamínicos H3/química , Receptores Histamínicos H3/genética , Receptores Histamínicos H3/metabolismo , Proteínas e Peptídeos Salivares/química , Homologia de Sequência de Aminoácidos , CarrapatosRESUMO
We report biopsy-proven resolution of immune-complex-mediated crescentic glomerulonephritis (ICMCGn) using mycophenolate mofetil (MMF). Therapy with steroids and cyclophosphamide failed twice in a 39-year-old white man who developed ICMCGn in his native kidneys, and subsequently in a human lymphocyte antigen-identical renal allograft. When he developed ICMCGn in a second, now cadaver, allograft, he was treated with steroids and MMF instead. His serum creatinine (Cr) improved from 4.4 mg/dL to 2.1 mg/dL. A biopsy 21 months later showed him to be free of glomerular disease. MMF is known to be an effective immunosuppressant. In our patient, ICMCGn, a notoriously difficult entity to treat effectively, seemingly resolved with MMF therapy. We suggest that MMF may be effective in the treatment of immunologically mediated pre-end-stage renal disease (ESRD). It should be considered in any posttransplantation setting where the original cause of organ failure is known to be immunologically mediated and likely to recur.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Glomerulonefrite/imunologia , Doenças do Complexo Imune/imunologia , Imunossupressores/uso terapêutico , Transplante de Rim/imunologia , Ácido Micofenólico/análogos & derivados , Adulto , Biópsia , Humanos , Glomérulos Renais/imunologia , Masculino , Ácido Micofenólico/uso terapêutico , Transplante Homólogo , Resultado do TratamentoRESUMO
The purpose of this investigation was to compare outcomes in the immediate posttransplant period for hemodialysis (HD) and peritoneal (PD) dialysis patients who received cadaveric renal transplantation. Data were obtained from the United Network of Organ Sharing on all cadaveric graft recipients who were dialysis-dependent at the time of transplantation between April 1994 and December 1995. Baseline characteristics were compared between groups, and multivariate logistic regression was performed with outcome measures including urine production in the first 24 h posttransplantation (U24), requirement for dialysis in the first week posttransplant (FWDIAL), and treatment for acute rejection during the initial hospitalization. The odds of oliguria (not producing urine in the first 24 h) were 1.49 (1.28 to 1.74) times higher in HD versus PD patients. After adjustment for other comorbid conditions including age, gender, race, HLA mismatch, time on dialysis, panel-reactive antibodies, and cold and warm ischemia time, the odds of oliguria were 1.60 (1.14 to 2.25) times higher in black HD patients compared with PD patients and 1.29 (1.06 to 1.57) times higher in white HD patients. In a similar manner, after adjustment for significant comorbid conditions, the odds of requiring dialysis in the first week were 1.56 (1.22 to 2.0) times higher in black HD patients versus PD patients and 1.40 (1.21 to 1.60) times higher in white HD patients. The rate of acute rejection was similar during the first hospitalization. These results suggest that there is an association between hemodialysis and delayed graft function. Differences in biocompatibility between the two modalities could potentially be responsible.