RESUMO
Despite the Organ Donation Breakthrough Collaborative's work to engage the transplant community and the suggested positive impact from these efforts, availability of transplanted organs over the past 5 years has declined. Living kidney, liver and lung donations declined from 2004 to 2008. Living liver donors in 2008 dropped to less than 50% of the peak (524) in 2001. There were more living donors that were older and who were unrelated to the recipient. Percentages of living donors from racial minorities remained unchanged over the past 5 years, but percentages of Hispanic/Latino and Asian donors increased, and African American donors decreased. The OPTN/UNOS Living Donor Transplant Committee restructured to enfranchise organ donors and recipients, and to seek their perspectives on living donor transplantation. In 2008, for the first time in OPTN history, deceased donor organs decreased compared to the prior year. Except for lung donors, deceased organ donation fell from 2007 to 2008. Donation after cardiac death (DCD) has accounted for a nearly 10-fold increase in kidney donors from 1999 to 2008. Use of livers from DCD donors declined in 2008 to 2005 levels. Understanding health risks associated with the transplantation of organs from 'high-risk' donors has received increased scrutiny.
Assuntos
Doadores de Tecidos/provisão & distribuição , Doadores de Tecidos/estatística & dados numéricos , Obtenção de Tecidos e Órgãos/estatística & dados numéricos , Obtenção de Tecidos e Órgãos/tendências , Negro ou Afro-Americano/estatística & dados numéricos , Hispânico ou Latino/estatística & dados numéricos , Humanos , Rim , Fígado , Doadores Vivos/estatística & dados numéricos , Pulmão , Grupos Minoritários/estatística & dados numéricos , Grupos Raciais , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Liver transplantation (LT) can significantly improve mortality for severe alcoholic hepatitis (AH). However, this practice remains controversial. Our aim is to report the findings from our institution regarding outcomes for LT in severe AH and to discuss the results of a pilot program for discharging selected patients with close follow-up, in order to demonstrate sustained outpatient sobriety before listing. METHODS: Patient records were reviewed retrospectively from January 1, 2015 to January 17, 2018. The primary outcomes were patient and graft survival after LT. Secondary outcomes included relapse rates after LT, survival for those not transplanted, and reasons for denial among those not approved for transplant listing. RESULTS: A total of 18 patients with severe AH were considered for LT, of which 10 were transplanted and 8 were either denied transplantation or died before completing the evaluation. Patient and graft survival rates were 100% among those transplanted, and only 1 of the 10 patients (10%) returned to harmful drinking. In comparison, 6 of 8 (75%) of patients not transplanted died. Among the 10 patients transplanted, 4 were initially not approved for listing and were discharged with close follow-up, to demonstrate outpatient sobriety. All 4 of those patients demonstrated short-term abstinence and ultimately underwent transplantation, with no instances of relapse post-LT. CONCLUSIONS: Liver transplantation for AH can achieve excellent outcomes with low rates of relapse. Carefully selected patients can be discharged with close monitoring to demonstrate commitment to outpatient sobriety prior to transplant listing.
Assuntos
Abstinência de Álcool/estatística & dados numéricos , Hepatite Alcoólica/cirurgia , Transplante de Fígado , Adulto , Feminino , Humanos , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Projetos Piloto , Recidiva , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Intraoperative extracorporeal membrane oxygenation (ECMO) support, both venoarterial and venovenous (VV), have been used sparingly and with limited success in the setting of liver transplantation. Here, we report the successful use of VV-ECMO in the resuscitation and pulmonary bridging support after severe systemic inflammatory response in a combined liver and kidney transplant recipient who suffered primary nonfunction of both allografts. Where conventional ventilator maneuvers may prove ineffective, the implementation of VV-ECMO should be considered as a therapeutic option in limited, short-lived acute pulmonary injury.
Assuntos
Oxigenação por Membrana Extracorpórea/métodos , Transplante de Fígado/efeitos adversos , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/terapia , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/terapia , Humanos , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/terapia , ReoperaçãoRESUMO
Endoscopic retrograde cholangiopancreatography (ERCP) is frequently employed in the management of postoperative biliary complications in the liver transplant patient. Bleeding after ERCP most commonly presents as gastrointestinal bleeding and often can be managed with repeat endoscopy. ERCP can also be complicated by retroperitoneal hematoma, which in rare cases can lead to hemodynamic compromise due to relentless hemorrhage or from secondary abdominal compartment syndrome. We describe the first reported case of post-ERCP retroperitoneal hematoma in a liver transplant recipient that led to abdominal compartment syndrome and shock liver. We will present the case, discuss management, and review the complications of ERCP in the liver transplant recipient. Close post-procedure monitoring, rapid detection, and low threshold for decompressive laparotomy are keys to the successful management of the liver transplant recipient experiencing expanding retroperitoneal hematoma after ERCP.
Assuntos
Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Síndromes Compartimentais/etiologia , Hematoma/etiologia , Transplante de Fígado/fisiologia , Espaço Retroperitoneal , Carcinoma Hepatocelular/cirurgia , Hematoma/complicações , Hepatite C/cirurgia , Humanos , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Preformed donor-specific human leukocyte antigen antibodies (DSAs) in patients undergoing simultaneous liver and kidney transplantation (SLKT) are an independent risk factor for poorer patient and renal allograft survival. The outcomes of patients highly sensitized (HS) against HLA antigens undergoing SLKT and select HS SLKT recipients undergoing desensitization at a high-volume desensitization center were investigated. METHODS: Seventy-five patients undergoing SLKT at a high-volume desensitization center between January 1, 2001, and December 31, 2015, were retrospectively reviewed. HS patients were defined by panel-reactive antibody (PRA) >30% (n = 17 patients), 11 of whom received pre- or perioperative desensitization with high-dose intravenous immunoglobulin (IVIG) ± rituximab. RESULTS: HS patients had significantly higher class I and class II PRA (class I = 41.3% ± 40.0% vs 2.5% ± 6.3%; class II = 45.7% ± 36.4% vs 1.0% ± 2.9%; P < .001), were more likely to be female (P = .05), and more likely to have had a prior transplant (P = .03). HS patients demonstrated greater susceptibility to renal cell-mediated rejection (CMR) (23.5% vs 5.2%, P = .02) compared to nonsensitized patients. Higher renal antibody-mediated rejection (ABMR) was also observed in HS patients, 11.8% vs 3.4%, but did not reach significance (P = .18). Desensitization in select HS SLKT patients was well tolerated but did not improve patient and allograft survival or significantly curtail rejection. CONCLUSION: HS SLKT recipients demonstrated increased allograft rejection, particularly CMR, but patient and graft survival were not impacted in the first year post-transplant. Select HS SLKT patients tolerated desensitization with high-dose IVIG ± rituximab and may have received additional immunoprotection against ABMR but survival was not affected.
Assuntos
Dessensibilização Imunológica/efeitos adversos , Sobrevivência de Enxerto , Imunoglobulinas Intravenosas/efeitos adversos , Transplante de Rim/métodos , Transplante de Fígado/métodos , Rituximab/efeitos adversos , Adulto , Anticorpos/imunologia , Dessensibilização Imunológica/métodos , Feminino , Sobrevivência de Enxerto/imunologia , Antígenos HLA/imunologia , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Transplante de Rim/efeitos adversos , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Rituximab/administração & dosagem , Doadores de Tecidos , Transplante Homólogo , Resultado do TratamentoRESUMO
The effect of treatment with the thymic factor thymostimulin (TP-1) on the survival rate of tumor-bearing mice was studied, using C57BL/6 mice inoculated with 1 x 10(5) Lewis lung carcinoma (3LL) cells. TP-1 given from inoculation day (4 mg/kg, twice weekly) caused a delay in the appearance of primary tumor [14.4 +/- 1.1 (S.E.) days in control; 18.5 +/- 1.4 days in TP-1-treated animals; p less than 0.05], without changing ultimate survival rate. When primary tumor was resected, the incidence of fatal lung metastasis increased as a function of tumor size on resection day. TP-1 given after resection (same dose schedule) significantly increased survival rate as compared to resection only, provided that resected tumor diameter was less than 1.7 mm. The combination of TP-1 and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU; single i.p. injection, 50 mg/kg) was effective in either resected or nonresected primary tumor. Without resection, TP-1 with CCNU cured (more than 6 months free of tumor; untreated animals died within 30 to 44 days) 55% of the animals, as compared to 23% cured by CCNU alone (p less than 0.01). With resection animal cure rates were: resection (resected tumor diameter, 0.7 to 1.7 mm) alone, 42% cured; resection with CCNU, 47% cured; resection with TP-1, 70% cured; resection with CCNU and TP-1, 100% cured (last two groups significantly different from resection only). The results indicate a profound effect of TP-1 in prolonging life and increasing cure of tumor-bearing mice. This effect was manifested when tumor load was small and was apparently more pronounced on metastatic than on primary tumor.
Assuntos
Neoplasias Experimentais/terapia , Extratos do Timo/uso terapêutico , Animais , Imunoterapia , Lomustina/uso terapêutico , Neoplasias Pulmonares/secundário , Masculino , Camundongos , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/cirurgiaRESUMO
Thymostimulin (TS), a partially purified thymic factor, has a significant impact on tumor development in C57B1/6 mice inoculated with Lewis lung carcinoma (3LL) cells, as judged by its effect on time of tumor appearance after tumor cell transplantation. In a previous study, we determined the conditions under which survival rate of the tumor-bearing mice can be significantly increased by TS treatment. In the study communicated here we analyzed host defense mechanisms that are modified by TS treatment in the tumor-bearing mice. In general, immune parameters that were increased or stimulated by the presence of the tumor were further increased in the TS-treated animals (number of lymphoid spleen cells, their response in mixed lymphocyte tumor cultures, their natural killer cell activity, and their ability to produce colony-stimulating factor), or reached earlier maximum levels (spontaneous [3H]thymidine incorporation, a reflection of in vivo spleen cell activation). Responses which reflect tumor-induced immunosuppression (proliferative response induced by phytohemagglutinin or concanavalin A stimulation) were restored to normal level by TS. Specific tumor-related reactions (specific cell-mediated cytotoxicity) were preserved in the TS-treated animals. The wide spectrum of TS effects had, nevertheless, certain elements of selectivity; e.g. colony-stimulating factor, but no interferon production is enhanced by TS in the tumor-bearing mice in diametric contrast to TS effect in Mengo virus-infected mice. The spectrum of TS effects was also dependent on the type of tumor cell used. The results indicate that the significant effect of TS on 3LL tumor development in mice is associated with a strong, multifaceted effect of TS on the immune system.
Assuntos
Carcinoma/imunologia , Imunidade Celular , Neoplasias Pulmonares/imunologia , Linfocinas/biossíntese , Extratos do Timo/farmacologia , Animais , Carcinoma/patologia , Fatores Estimuladores de Colônias/biossíntese , Citotoxicidade Imunológica , Interferons/biossíntese , Células Matadoras Naturais/imunologia , Lectinas/farmacologia , Ativação Linfocitária , Masculino , Camundongos , Baço/patologia , Linfócitos T Citotóxicos/imunologiaRESUMO
The association of a receptor (Rs) of the Spm system with a Bz-1 allele has created a two-element Spm-controlled bz-mutable allele (bz-m13) of maize (Zea mays L.). In the absence of Spm, one copy of bz-m13 (bz/bz/bz-m13 ) conditions full anthocyanin production in the aleurone layer of the seed. In the presence of this Spm, bz-m13 produces a unique, coarsely variegated seed phenotype and has a high rate (50-83%) of gametic change to stable bz' or Bz' derivatives. Even one copy of a Bz' derivative allele conditions full anthocyanin production in the aleurone, but the enzyme (UFGT) level of the progenitor Bz-1 allele is not restored in most Bz' derivatives.
RESUMO
The Ds-controlled allele, bz-m4 Derivative 6856 [bz-m4 D6856], is reported to have an altered temporal- and tissue-specific pattern of gene expression. We have cloned this allele and have characterized it at the molecular level. The mutation was caused by the insertion of a complex transposon-like structure 36 base pairs downstream from the Bz mRNA cap site. The insert is 6.7-kbp long. Ds elements, each approximately 2 kbp in length, are at both ends of the insert. The sequence between the Ds elements is a partial duplication of flanking sequences from the 3' end of the Bz gene. These data suggest that Ds initially inserted near the 3' end of the gene and mobilized adjacent sequences as it transposed.
Assuntos
Elementos de DNA Transponíveis , Regulação da Expressão Gênica , Glucosiltransferases/genética , Mutação , Zea mays/genética , Sequência de Bases , Southern Blotting , Clonagem Molecular , Escherichia coli/genética , Modelos Genéticos , Dados de Sequência Molecular , Mapeamento por RestriçãoRESUMO
Fungal infections are characteristic of severely immunocompromised patients. Noncandidal yeasts represent a growing proportion of such infections. Risk factors for developing fungal infections include the use and abuse of central venous catheters. Two patients with gynecologic malignant neoplasms became fungemic with Hansenula anomala, a yeast of the Ascomycetes class, after insertion of central venous catheters. Frequent catheter manipulation and prolonged use favored the development of fungemia in both patients. A review of the literature revealed 19 additional cases over the course of four decades, all in hosts with underlying diseases. Thirteen of these cases have been described in the last 18 months, suggesting either increased recognition or increased frequency of infection with this organism. All tested isolates have been susceptible to amphotericin B. Patients have generally responded to catheter withdrawal and amphotericin B administration. Hansenula anomala is an opportunistic pathogen, whose clinical behavior resembles that of Candida species.
Assuntos
Micoses , Infecções Oportunistas , Sepse/etiologia , Feminino , Humanos , Pessoa de Meia-Idade , PichiaRESUMO
Liver transplantation in patients infected with the human immunodeficiency virus (HIV) has been increasingly performed with reasonable outcomes; however, medical management of both immunosuppression and antiretroviral therapy can be challenging owing to drug toxicities and interactions. Nucleoside reverse transcriptase inhibitors (NRTIs), a common backbone of highly active antiretroviral therapy (HAART), were the first class of effective antiretroviral drugs developed. NRTIs are commonly used for posttransplant HAART therapy and have a rare but fatal complication of mitochondrial toxicity, manifesting as severe lactic acidosis, hepatic steatosis, and lipoatrophy. Herein, we have reported on the first known successful treatment of severe mitochondrial toxicity secondary to NRTIs in an HIV-infected transplant recipient.
Assuntos
Terapia Antirretroviral de Alta Atividade/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/terapia , Infecções por HIV/tratamento farmacológico , Transplante de Fígado/efeitos adversos , Mitocôndrias Hepáticas/efeitos dos fármacos , Doenças Mitocondriais/terapia , Carcinoma Hepatocelular/cirurgia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Infecções por HIV/virologia , Humanos , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Doenças Mitocondriais/induzido quimicamente , Carga ViralRESUMO
BACKGROUND: Infection is the most common cause of mortality in end-stage liver disease (ESLD). The impact of obesity on infection risk in ESLD is not established. AIM: To characterise the impact of obesity on infection risk in ESLD. METHODS: We evaluated the association between infection and obesity in patients with ESLD. Patients grouped as non-obese, obesity class I-II and obesity class III were studied using the Nationwide Inpatient Sample. Validated diagnostic code based algorithms were utilised to determine weight category and infections, including bacteraemia, skin/soft tissue infection, urinary tract infection (UTI), pneumonia/respiratory infection, Clostridium difficile infection (CDI) and spontaneous bacterial peritonitis (SBP). Risk factors for infection and mortality were assessed using multivariable logistic regression analysis. RESULTS: Of 115 465 patients identified, 100 957 (87.5%) were non-obese and 14 508 (12.5%) were obese, with 9489 (8.2%) as obesity class I-II and 5019 (4.3%) as obesity class III. 37 117 patients (32.1%) had an infection diagnosis. Infection was most prevalent among obesity class III (44.0%), followed by obesity class I-II (38.9%) and then non-obese (31.9%). In multivariable modelling, class III obesity (OR = 1.41; 95% CI 1.32-1.51; P < 0.001), and class I-II obesity (OR = 1.08; 95% CI 1.01-1.15; P = 0.026) were associated with infection. Compared to non-obese patients, obese individuals had greater prevalence of bacteraemia, UTI, and skin/soft tissue infection as compared to non-obese patients. CONCLUSIONS: Obesity is newly identified to be independently associated with infection in end-stage liver disease. The distribution of infection sites varies based on weight category.
Assuntos
Infecções Bacterianas/epidemiologia , Doença Hepática Terminal/complicações , Obesidade/complicações , Idoso , Infecções por Clostridium/epidemiologia , Bases de Dados Factuais , Feminino , Humanos , Pacientes Internados , Masculino , Pessoa de Meia-Idade , Pneumonia/epidemiologia , Prevalência , Fatores de RiscoRESUMO
This study was designed to quantitatively discriminate the specific xanthine oxidase (XO) inhibitory from the relatively nonspecific antioxidant activities of allopurinol, both in vitro and in vivo in the rat. XO activity, determined by the spectrophotometric assay for urate generation over time, was completely inhibited in vitro by allopurinol at concentrations > or = 200 microM. Allopurinol's antioxidant activity was determined in vitro using a linolenic acid peroxidation (LAP) assay. Although the known antioxidant butylated hydroxytoluene effectively inhibited LAP (80% inhibition of malondialdehyde generation at 10(1) microM), allopurinol (10(1)-10(3) microM) did not inhibit this LAP (p < .01). Rat serum obtained after oral administration of allopurinol (100 mg/kg x 2 doses) did not suppress LAP in vitro more than did control rat serum. Following oral administration of allopurinol (2-50 mg/kg x 2 doses), dose-dependent inhibition of XO activity was observed in the homogenates of the liver (to 5% of control level; p < .001) and the intestine (to 12% of control level; p < .001). We conclude that while 2-50 mg/kg of oral allopurinol effectively suppresses XO activity in the rat liver and intestine, antioxidant activity is not seen even in doses up to 100 mg/kg. The selective enzymatic inhibitory effect of allopurinol at these doses therefore should provide a useful tool to allow the discrimination of the effects of xanthine oxidase in particular from the effects of reactive oxygen metabolites in general.
Assuntos
Alopurinol/farmacologia , Antioxidantes/farmacologia , Inibidores Enzimáticos/farmacologia , Xantina Oxidase/antagonistas & inibidores , Animais , Hidroxitolueno Butilado/farmacologia , Feminino , Radicais Livres/metabolismo , Técnicas In Vitro , Mucosa Intestinal/metabolismo , Intestinos/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Malondialdeído/metabolismo , Ratos , Ratos Endogâmicos Lew , Ácido alfa-Linolênico/metabolismoRESUMO
Phagocytosis and killing of circulating organisms by Kupffer cells (KCs) are discrete, important components of host defense. However, the killing mechanism(s) are not fully understood, and the potential role of adjacent nonparenchymal cells such as hepatic endothelial cells has not been defined. Rat KCs -/+ an hepatic endothelial cell enriched cellular fraction (HECEF) were incubated with Candida parapsilosis and assayed for phagocytosis and phagocytic killing by validated fluorochromatic vital staining. The role of reactive oxygen metabolites in KC phagocytic functions was examined by inhibition with superoxide dismutase and/or catalase. Diphenyleneiodonium and allopurinol were used to examine the potential roles of NADPH oxidase and xanthine oxidase, respectively, in generating these toxic oxidants. Coculture with HECEF increased KC phagocytic activity (from 75% to 88%) and candidacidal activity (from 20% to 31%). Superoxide dismutase, catalase, diphenyleneiodonium, or allopurinol caused inhibition of candidacidal activity, but did not affect phagocytosis, and did not block the potentiation of phagocytosis or of killing caused by coculture with HECEF. Reactive oxygen intermediates generated by both NADPH oxidase and xanthine oxidase-dependent pathways are important in KC killing of Candida parapsilosis. In vitro, KC phagocytosis and killing are potentiated (via a non-oxidant-mediated mechanism) by coculture with a preparation of hepatic non-parenchymal cells composed primarily of endothelial cells.
Assuntos
Células de Kupffer/fisiologia , Oxidantes/metabolismo , Fagocitose/fisiologia , Alopurinol/farmacologia , Animais , Candida/imunologia , Catalase/farmacologia , Técnicas de Cocultura , Endotélio/citologia , Endotélio/fisiologia , Radicais Livres/metabolismo , Células de Kupffer/efeitos dos fármacos , Células de Kupffer/imunologia , Masculino , NADPH Oxidases/metabolismo , Oniocompostos/farmacologia , Fagocitose/efeitos dos fármacos , Ratos , Ratos Endogâmicos Lew , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/farmacologia , Xantina Oxidase/metabolismoRESUMO
A major component of the organ injury mediated by toxic oxidants, such as seen following reperfusion of the ischemic liver, is due to the peroxidation of polyunsaturated fatty acids, especially of cell membranes. We utilized the measurement of exhaled breath ethane, a metabolic product unique to oxidant-mediated lipid peroxidation, as a noninvasive indicator of this process in swine liver subjected to warm ischemia/reperfusion. Under rigorously controlled anesthesia conditions, pig livers were subjected to 2 h of warm total ischemia, followed by reperfusion in situ. Expired air was collected and its ethane content quantitated by a novel gas chromatographic technique. The time course of breath ethane generation correlated closely with the appearance of hepatocellular injury as measured by impairment of Factor VII generation and other measures of liver integrity. Moreover, the administration of the specific superoxide free radical scavenger, superoxide dismutase (SOD), significantly attenuated both the elaboration of ethane and the hepatocellular injury. These findings not only provide confirmation of the previously reported link between hepatocellular injury by free radicals generated at reperfusion, but also establish the use of expired breath ethane analysis as a sensitive, specific, and noninvasive indicator of the injury process in real time.
Assuntos
Etano/análise , Isquemia/metabolismo , Peroxidação de Lipídeos , Fígado/irrigação sanguínea , Fígado/metabolismo , Traumatismo por Reperfusão/metabolismo , Reperfusão , Respiração , Alanina Transaminase/sangue , Amônia/sangue , Animais , Aspartato Aminotransferases/sangue , Bile/metabolismo , Bilirrubina/sangue , Biomarcadores , Radicais Livres , Cinética , Traumatismo por Reperfusão/diagnóstico , Suínos , Fatores de TempoRESUMO
Fatal mushroom poisoning has long been recognized as a major health problem in western Europe and more recently in the United States. The majority of deaths are attributable to the genus Amanita. Amanita phalloides (death cap) has been found with increasing frequency across the United States and presents a significant health hazard in this country to those who pick and consume wild mushrooms. This article discusses the pharmacologic basis and clinical manifestations of Amanita intoxication. It outlines the rationale of various treatment modalities and, from these, summarizes a protocol that the authors believe will be useful to the clinician. In addition, two patients are presented who underwent successful orthotopic liver transplantation for fulminant hepatic failure secondary to Amanita poisoning. The role of liver transplantation both acutely and as treatment for chronic active hepatitis secondary to severe intoxication is discussed.
Assuntos
Transplante de Fígado , Intoxicação Alimentar por Cogumelos/terapia , Adulto , Amanita , Feminino , Hidratação , Lavagem Gástrica , Encefalopatia Hepática/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Intoxicação Alimentar por Cogumelos/tratamento farmacológico , Intoxicação Alimentar por Cogumelos/cirurgia , Micotoxinas/farmacologiaRESUMO
A critical role of the complement membrane attack complex (C5b-9) in mediating hyperacute rejection has been demonstrated previously in fully C6-deficient PVG (C-)(RT1c) rats that reject guinea pig cardiac xenografts at a delayed tempo (45 +/- 9 hr; n=16) compared with C6-sufficient PVG (C+)(RT1c) hosts (0.5 +/- 2 hr; n=6). We have investigated whether selective depletion of C6 from Lewis rats by antibody therapy prevents hyperacute rejection. A polyclonal rat-antirat C6 antibody was induced in PVG (C-) recipients by orthotopic liver transplants from congenic PVG (C+) donors. These liver grafts produced high levels of C6 that reconstituted the complement function of PVG (C-) hosts by 7 days, but the recipients responded within 28 days with the synthesis of an IgG1 antibody to rat C6. The antiserum inhibited hemolytic complement activity of Lewis (RT1(1)) rats in vivo and in vitro. The effect of C6 depletion on Xg survival was investigated by injecting Lewis rats with 2 ml of rat-antirat C6 antiserum before and 1 ml after reperfusion of the guinea pig cardiac xenograft. Lewis rats rejected guinea pig cardiac xenografts after treatment with this rat-antirat C6 antiserum in 38 +/ -11 hr (n=3). Treatment with normal control sera from PVG (C-) rats did not prolong guinea pig cardiac xenograft survival in the Lewis rats (1 +/- 0.7 hr; n=3)(P<0.0043). Injection of 3 ml of the IgG fraction purified from the rat-antirat C6 antibody (33 mg/ml) prolonged xenograft survival to 13.6 +/- 4 hr (n=4) compared with the survival of 0.61 +/- 0.3 hr (n=4) after injection of control rat IgG (33 mg/ml) (P<0.005). These results demonstrate that specific depletion of C6 by antibody therapy has a significant effect on guinea pig cardiac xenograft survival in the Lewis rat. These findings further suggest that C6 depletion may be beneficial to patients undergoing hyperacute rejection of xenografts or allografts.
Assuntos
Anticorpos/fisiologia , Complemento C6/deficiência , Transplante de Fígado/imunologia , Animais , Anticorpos/sangue , Anticorpos/farmacologia , Anticorpos Monoclonais/farmacologia , Formação de Anticorpos , Western Blotting , Complemento C6/imunologia , Ensaio de Atividade Hemolítica de Complemento , Sobrevivência de Enxerto/imunologia , Cobaias , Transplante de Coração , Masculino , Ratos , Ratos Endogâmicos Lew , Transplante HeterólogoRESUMO
This study focuses upon two discrete components of posttransplant hepatic reticuloendothelial system (RES) function-phagocytosis and killing of bacteria-under various conditions of ischemic preservation. We had previously reported that, following intravenous injection of rats with 51Cr and 125I double-labeled Escherichia coli, hepatic 51Cr levels can be used to reliably quantify hepatic phagocytic clearance of the bacteria from the blood (HPC), while the subsequent release of 125I from the liver accurately parallels hepatic bacterial killing. Here, Wistar rats were transplanted with syngeneic livers perfused with either normal saline (NS) or University of Wisconsin solution (UW) and stored at 4 degrees C for 1, 2, or 3 hr prior to implantation. Control rats underwent laparotomy and hepatic artery ligation. Using the double-labeled E coli assay, HPC was decreased in all transplanted animals when compared with controls, reaching a nadir on the third postoperative day (P < 0.05). In rats transplanted with livers preserved in NS, the fraction of phagocytosed organisms that were subsequently killed (hepatic killing efficiency=HKE) was increased to 142%, 129%, or 112% of normal following 1, 2, or 3 hr of cold ischemia, respectively; P < 0.05). Conversely, preservation of donor allografts in UW was associated with marked depression of HKE. Moreover, rats receiving NS- or UW-preserved livers tolerated an intravenous challenge with Streptococcus pneumoniae poorly (50% mortality) compared with hepatic artery ligated controls (12% mortality) at 7 days. Ischemic preservation of rat livers in NS resulted in a dose (of ischemia)-dependent reduction of hepatic phagocytosis coupled with a potentiation of HKE. Preservation in UW, however, produced a striking suppression of both components of hepatic RES function. Following a septic challenge survival was reduced in both groups of transplanted rats.
Assuntos
Células de Kupffer/fisiologia , Transplante de Fígado , Fígado/microbiologia , Soluções para Preservação de Órgãos , Traumatismo por Reperfusão/microbiologia , Adenosina , Alopurinol , Animais , Escherichia coli , Infecções por Escherichia coli/fisiopatologia , Glutationa , Insulina , Células de Kupffer/microbiologia , Fígado/patologia , Masculino , Fagocitose , Rafinose , Ratos , Ratos Wistar , Traumatismo por Reperfusão/fisiopatologia , Preservação de TecidoRESUMO
BACKGROUND: The spectrum of disease caused by Ehrlichia spp. ranges from asymptomatic to fatal. Awareness and early diagnosis of the infection is paramount because appropriate therapy leads to rapid defervescence and cure. If left untreated, particularly in immunosuppressed patients, ehrlichioses may result in multi-system organ failure and death. METHODS: We report the second case of human monocytic ehrlichiosis (HME) in a liver transplant recipient, and review the literature. RESULTS: The patient presented with fever and headache, had negative cultures, and despite broad-spectrum antimicrobial coverage appeared progressively septic. After eliciting a history of tick exposure we treated the patient empirically with doxycycline. The diagnosis of HME was confirmed by 1) polymerase chain reaction (PCR) for Ehrlichia chaffeensis, 2) acute and convalescent serum titers, and 3) in vitro cultivation of E chaffeensis from peripheral blood. CONCLUSION: Although human ehrlichioses are relatively uncommon, they are emerging as clinically significant arthropod-borne infections. Although epidemiological exposure is responsible for infection, immunosuppression makes patients more likely to succumb to disease. A high index of suspicion and early treatment results in a favorable outcome.
Assuntos
Ehrlichiose/etiologia , Terapia de Imunossupressão/efeitos adversos , Transplante de Fígado , Monócitos/microbiologia , Animais , Mordeduras e Picadas/complicações , Ehrlichiose/patologia , Humanos , Masculino , Pessoa de Meia-Idade , CarrapatosRESUMO
BACKGROUND: The role of plasmapheresis in liver failure and hepatic coma remains controversial. Also, its use as a salvage strategy for patients with severe allograft dysfunction after liver transplantation has not been defined. This report reviews the use of plasmapheresis in primary hepatic allograft nonfunction (PNF). METHODS: From May of 1997 to October of 1998, five patients underwent plasmapheresis for PNF after other causes of immediate allograft dysfunction were excluded. These patients underwent two to five plasmapheresis procedures during which one plasma volume was removed and replaced with fresh frozen plasma (FFP) or with 50% FFP and 50% albumin. RESULTS: All recipients who underwent plasmapheresis had restoration of liver function. There was one death from pulmonary embolism, for an overall survival rate of 80%. The four surviving patients all had functioning allografts 1 year after liver transplantation. In contrast, during the same period, there were two patients in whom PNF was treated by retransplantation, and both died within 3 months after surgery with functioning allografts. CONCLUSIONS: Plasmapheresis provides an effective treatment option for PNF immediately after liver transplantation and may obviate the need for retransplantation.