Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 30
Filtrar
1.
Med Mycol Case Rep ; 22: 27-29, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30101055

RESUMO

We present the first cirrhotic patient who underwent liver transplantation (LT) and presented a hepatic artery thrombosis of the graft due to Aspergillus fumigatus, within the first month of LT. This culminated in graft loss, re-transplant with multiple biliary and infectious complications. To our knowledge, this is a case report of an early hepatic artery thrombosis due to Aspergillus fumigatus in an infection-free patient.

2.
Am J Case Rep ; 19: 669-672, 2018 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-29884776

RESUMO

BACKGROUND Lysosomal acid lipase deficiency is a rare genetic metabolic lipid storage disease, with a high morbidity, and mortality, in children and adults. It is characterized by a mutation in the LIPA gene that causes an alteration of lipid metabolism, resulting in deposits of cholesterol esters and triglycerides in organs such as the liver, blood vessels, and gastrointestinal tract. Lysosomal acid lipase deficiency is predominantly caused by the mutation c.894G>A, seen in approximately 50-70% of patients. Our objective is to report the first pediatric case of lysosomal acid lipase deficiency in a pediatric patient in Colombia. CASE REPORT The patient is a 14-year-old boy with isolated hepatomegaly since 6 years of age without a family history of dyslipidemia. In the pediatric control, laboratory exams revealed dyslipidemia, and a hepatic biopsy was performed, revealing severe fibrosis with septation and grade 3 microvesicular steatosis (>75%). He was referred to our center and was suspected to have lysosomal acid lipase deficiency. Enzymatic activity was measured, showing absent activity. Confirmatory diagnosis with genetic sequencing showed a pathological homozygous mutation of c.894G>A. CONCLUSIONS Lysosomal acid lipase deficiency can manifest as early- or late-onset, with variable and severe signs and symptoms. The late-onset form has a broad spectrum of manifestations with mild symptoms, leading to under-diagnosis, which increases the actual disease burden. Early diagnosis is essential to initiate enzyme replacement therapy, since the natural disease course can be changed. More studies should be conducted in Latin America to evaluate the prevalence of the disease.


Assuntos
Esterol Esterase/genética , Doença de Wolman/diagnóstico , Adolescente , Colômbia , Fígado Gorduroso/genética , Hepatomegalia/genética , Humanos , Masculino , Mutação , Esterol Esterase/deficiência , Doença de Wolman/complicações , Doença de Wolman/genética , Doença de Wolman
3.
Am J Transplant ; 18(8): 1947-1953, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29509285

RESUMO

Blood group B candidates, many of whom represent ethnic minorities, have historically had diminished access to deceased donor kidney transplantation (DDKT). The new national kidney allocation system (KAS) preferentially allocates blood group A2/A2B deceased donor kidneys to B recipients to address this ethnic and blood group disparity. No study has yet examined the impact of KAS on A2 incompatible (A2i) DDKT for blood group B recipients overall or among minorities. A case-control study of adult blood group B DDKT recipients from 2013 to 2017 was performed, as reported to the Scientific Registry of Transplant Recipients. Cases were defined as recipients of A2/A2B kidneys, whereas controls were all remaining recipients of non-A2/A2B kidneys. A2i DDKT trends were compared from the pre-KAS (1/1/2013-12/3/2014) to the post-KAS period (12/4/2014-2/28/2017) using multivariable logistic regression. Post-KAS, there was a 4.9-fold increase in the likelihood of A2i DDKT, compared to the pre-KAS period (odds ratio [OR] 4.92, 95% confidence interval [CI] 3.67-6.60). However, compared to whites, there was no difference in the likelihood of A2i DDKT among minorities post-KAS. Although KAS resulted in increasing A2/A2B→B DDKT, the likelihood of A2i DDKT among minorities, relative to whites, was not improved. Further discussion regarding A2/A2B→B policy revisions aiming to improve DDKT access for minorities is warranted.


Assuntos
Incompatibilidade de Grupos Sanguíneos , Implementação de Plano de Saúde , Transplante de Rim/mortalidade , Grupos Minoritários/estatística & dados numéricos , Alocação de Recursos/normas , Doadores de Tecidos/provisão & distribuição , Listas de Espera/mortalidade , Feminino , Seguimentos , Humanos , Isoanticorpos/imunologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida , Obtenção de Tecidos e Órgãos/tendências , Transplantados
5.
Transpl Infect Dis ; 20(2): e12842, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29359844

RESUMO

Hepatitis A virus (HAV) causes an acute infection and is usually asymptomatic in children. When clinical manifestations appear, these include choluria, jaundice, and abdominal pain. Although infrequent, extra-hepatic manifestations related to HAV have been described, affecting the heart, bone marrow, blood vessels, and other tissues.A 10-year-old boy from a rural area presented with a 15-day history of malaise, fever, and jaundice; laboratory examinations were compatible with HAV infection. The patient turned encephalopathic and was remitted to our center, where laboratory examinations showed a medullary aplasia and fulminant hepatitis requiring a liver transplant that was performed 72 hours after admission. At 24 hours post transplant, the patient developed a cardiomyopathy secondary to HAV, and intravenous immunoglobulin was administered. The patient is still alive and attending his medical check-ups.Although rare, extra-hepatic manifestations of HAV infection have been described in 14% of cases. The groups of patients affected are usually aged and present with high bilirubin levels. Acquired aplastic anemia and myocarditis caused by HAV are uncommon, and its pathophysiology has not yet been elucidated.HAV infection is usually asymptomatic in children, although extra-hepatic manifestations can appear requiring early detection and management.


Assuntos
Anemia Aplástica/complicações , Cardiomiopatias/etiologia , Hepatite A/complicações , Imunoglobulinas Intravenosas/uso terapêutico , Falência Hepática Aguda/complicações , Cardiomiopatias/terapia , Criança , Hepatite A/terapia , Humanos , Transplante de Fígado , Masculino
6.
Transplant Direct ; 3(6): e165, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28620649

RESUMO

BACKGROUND: Hepatoblastoma is the most common primary malignant liver tumor in children and is usually diagnosed during the first 3 years of life. Overall survival has increased 50% due to chemotherapeutic schemes, expertise surgery centers, and liver transplantation. METHODS: A retrospective collection of data was performed from pediatric patients with diagnosis of hepatoblastoma. Variables included demographic, diagnostic tools and histological classification; chemotherapy and surgical treatment; and outcomes and patient survival. The PRETEXT classification was applied, which included the risk evaluation, and according to the medical criterion in an individualized way, underwent resection or transplant. The morbidity of patients was evaluated by the Clavien-Dindo classification. Statistical analysis was performed according to the distribution of data and the survival analysis was carried out using the Kaplan-Meier method. RESULTS: The patients (n = 16) were divided in a resection group (n = 8) and a transplant group (n = 8). The median age at the time of diagnosis was 13.5 months. The motive for the initial consultation was the discovery of a mass; all patients had high levels of α-fetoprotein and an imaging study. Ten of 16 patients required chemotherapy before the surgical procedure. In the resection group, 5 of 8 patients were classified as Clavien I and 4 of 8 patients of the transplant group were classified as Clavien II. Patient survival at 30 months was 100% in the resection group and 65% in the liver transplantation group. CONCLUSIONS: To our knowledge, this is the first case report of pediatric patients with hepatoblastoma and liver resection or transplant in Colombia and Latin America. Our results are comparable with the series worldwide, showing that resection and transplant increase the survival of the pediatric patients with hepatoblastoma. It is important to advocate for an increase of reporting in the scientific literature in Latin America.

7.
J Appl Physiol (1985) ; 122(6): 1406-1417, 2017 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-28336538

RESUMO

Derangements of microvascular blood flow distribution might contribute to disturbing O2 extraction by peripheral tissues. We evaluated the dynamic relationships between the mesenteric O2 extraction ratio ([Formula: see text]) and the heterogeneity of microvascular blood flow at the gut and sublingual mucosa during the development and resuscitation of septic shock in a swine model of fecal peritonitis. Jejunal-villi and sublingual microcirculation were evaluated using a portable intravital-microscopy technique. Simultaneously, we obtained arterial, mixed-venous, and mesenteric blood gases, and jejunal-tonometric measurements. During resuscitation, pigs were randomly allocated to a fixed dose of dobutamine (5 µg·kg-1·min-1) or placebo while three sham models with identical monitoring served as controls. At the time of shock, we observed a significant decreased proportion of perfused intestinal-villi (villi-PPV) and sublingual percentage of perfused small vessels (SL-PPV), paralleling an increase in [Formula: see text] in both dobutamine and placebo groups. After starting resuscitation, villi-PPV and SL-PPV significantly increased in the dobutamine group with subsequent improvement of functional capillary density, whereas [Formula: see text] exhibited a corresponding significant decrease (repeated-measures ANOVA, P = 0.02 and P = 0.04 for time × group interactions and intergroup differences for villi-PPV and [Formula: see text], respectively). Variations in villi-PPV were paralleled by variations in [Formula: see text] (R2 = 0.88, P < 0.001) and these, in turn, by mesenteric lactate changes (R2 = 0.86, P < 0.001). There were no significant differences in cardiac output and systemic O2 delivery throughout the experiment. In conclusion, dynamic changes in microvascular blood flow heterogeneity at jejunal mucosa are closely related to the mesenteric O2 extraction ratio, suggesting a crucial role for microvascular blood flow distribution on O2 uptake during development and resuscitation from septic shock.NEW & NOTEWORTHY Our observations suggest that dynamic changes in the heterogeneity of microvascular blood flow at the gut mucosa are closely related to mesenteric O2 extraction, thus supporting the role of decreasing functional capillary density and increased intercapillary distances on alterations of O2 uptake during development and resuscitation from septic shock. Addition of a low-fixed dose of dobutamine might reverse such flow heterogeneity, improving microcirculatory flow distribution and tissue O2 consumption.


Assuntos
Dobutamina/farmacologia , Intestinos/irrigação sanguínea , Intestinos/efeitos dos fármacos , Microcirculação/efeitos dos fármacos , Oxigênio/metabolismo , Fluxo Sanguíneo Regional/efeitos dos fármacos , Choque Séptico/tratamento farmacológico , Animais , Gasometria/métodos , Débito Cardíaco/efeitos dos fármacos , Feminino , Hemodinâmica/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Consumo de Oxigênio/efeitos dos fármacos , Ressuscitação/métodos , Choque Séptico/metabolismo , Suínos
8.
Int J Surg Case Rep ; 33: 135-138, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28315818

RESUMO

INTRODUCTION: Sclerosing Encapsulating Peritonitis (SEP) is a rare condition with an incidence of up to 3% and a mortality of up to 51% among peritoneal dialysis (PD) patients (Brown et al., Korte et al. and Kawanishi et al.). In the last ten years, the incidence of SEP in kidney transplant recipients has increased (Nakamoto, de Sousa et al. and Korte et al.). PRESENTATION OF CASE: A 31-year old male with a 15 years history of PD and later kidney retransplantation was admitted to the emergency service after experiencing several weeks of diffuse abdominal pain which had escalated to include vomiting and diarrhea during the 24h previous to admission. The patient underwent an exploratory laparotomy where severe peritoneal thickening was found, in addition to signs of chronic inflammation and blocked intestinal loops. Histopathologic findings were suggestive of sclerosing peritonitis. After two months of treatment in hospital, the patient presented an obstructed intestine, with a rigid and thickened peritoneum compromising all the intestinal loops. DISCUSSION: Despite being rare, SEP, represents a significant complication due to its high mortality and recurrence. It is insidious in its early stages and culminates in an intestinal obstruction (Fieren). Risk factors for its development in kidney transplant recipients include a history of prolonged treatment with PD and the use of calcineurin inhibitors as an immunosuppressive treatment (Korte et al.). CONCLUSION: Given the increase in the incidence of SEP in kidney transplant recipients, the clinician should be alert to the presence of this complication. A greater number of multi-centre studies are required to identify the risk factors for SEP that are inherent in renal transplant recipients.

9.
Rev. nefrol. diál. traspl ; 37(1): 67-69, mar. 2017.
Artigo em Espanhol | LILACS | ID: biblio-1006397

RESUMO

El trasplante renal es el tratamiento de elección para los pacientes con enfermedad renal terminal. El trasplante con donante vivo, es la mejor opción para los receptores al implicar menor morbi-mortalidad y disminución del tiempo en lista activa. A pesar que el riesgo de ser donante vivo ha sido determinado y es bajo, se debe realizar una evaluación médica a los posibles donantes para identificar factores de riesgo para desarrollar insuficiencia renal crónica. En este reporte se describe un paciente quien fue donante y 21 años después desarrolló insuficiencia renal crónica (IRC) avanzada secundaria a hipertensión arterial no tratada por lo que fue trasplantado


Kidney transplant is the first-line therapy for end-stage renal disease. Living-donor transplant is the best choice for recipients as it reduces morbidity and mortality and the time spent on the active waitlist. Although it is known that the risk of being a living donor is low, a medical evaluation must be performed in order to identify risk factors for the development of chronic kidney disease. We report a case of a patient who was a donor and 21 years later presented advanced chronic kidney disease (CKD) following untreated high blood pressure. For this reason, the patient underwent a transplant


Assuntos
Humanos , Transplante de Rim , Sobrevivência de Enxerto
10.
Am J Case Rep ; 18: 114-118, 2017 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-28148909

RESUMO

BACKGROUND En-bloc transplantation is a surgical procedure in which multiple organs are transplanted simultaneously. It has some similarities with multi-organ transplantation but offers certain advantages. This report highlights the experience of our interdisciplinary group regarding the treatment and follow-up of patients who received en-bloc transplantation, with the aim of encouraging the development of this surgical technique. CASE REPORT The first case is a 38-year-old patient with type 1 diabetes mellitus, liver cirrhosis, and chronic kidney failure who received an en-bloc transplant of the liver, pancreas, and kidney with no intraoperative complications. He had a prolonged hospital stay due to anemia and systemic inflammatory response syndrome, which were resolved successfully. At follow-up, he had no requirement for insulin or for dialysis, or for new interventions. The second case describes a 48-year-old patient with type 2 diabetes mellitus, renal failure, and liver cirrhosis who received an en-bloc transplant of the liver, pancreas, and kidney with no complications. During the postoperative period, the patient suffered a possible episode of acute tubular necrosis, which evolved towards improvement, with a tendency to normal metabolic and renal functioning, with no additional events. The patient is currently in follow-up and is insulin-independent. CONCLUSIONS En-bloc transplantation is a safe procedure, which is technically simple and which achieves excellent results. This procedure is indicated in patients with end-stage renal disease, cirrhosis, and diabetes mellitus that is difficult to control.


Assuntos
Diabetes Mellitus Tipo 1/cirurgia , Diabetes Mellitus Tipo 2/cirurgia , Falência Renal Crônica/cirurgia , Transplante de Rim , Cirrose Hepática/cirurgia , Transplante de Fígado , Transplante de Pâncreas , Adulto , Humanos , Transplante de Rim/métodos , Transplante de Fígado/métodos , Masculino , Pessoa de Meia-Idade , Transplante de Pâncreas/métodos , Resultado do Tratamento
11.
Int J Surg Case Rep ; 28: 165-168, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27718433

RESUMO

INTRODUCTION: Liver angiosarcoma is a very uncommon tumour of mesenchymal origin, representing between 0.1-2% of all primary tumours of the liver, affecting mainly men in their sixth or seventh decade of life, with a high mortality in the first years (Chaudhary et al., 2015). Literature reports of its surgical treatment vary from a total or partial hepatectomy with or without liver transplant. PRESENTATION OF CASE: A 37year old male, with a 7year history of a fatty liver, was found to have a 12cm diameter tumour in a cirrhotic liver, during an abdominal Computed Tomography (CT) scan. Patient was asymptomatic with negative tumour markers, yet tumour liver biopsy revealed a Liver Angiosarcoma with positive immunohistochemistry for neoplastic cells CD31 and CD34. Patient was deemed candidate for a partial hepatectomy of the affected liver segments which was done without complications and no evidence of other tumour lesions was found during surgery. Patient continued oncologic management with ongoing chemotherapy. DISCUSION: Liver Angiosarcoma, although rare, persists with a high mortality due to its aggressive nature. Never the less liver transplantation, although proven to be an effective treatment for many pathologies that culminate in liver failure, fails to improve patients' survival and prognosis, when compared to partial hepatectomy as surgical management to for liver Angiosarcoma, CONCLUSION: Partial hepatectomy as surgical management, followed by adjuvant therapy, for Liver Angiosarcoma continues to prove favourable results and prognosis compared to Liver Transplantation.

12.
Int J Surg Case Rep ; 28: 192-195, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27718439

RESUMO

INTRODUCTION: One of the frequent complications suffered by patients with chronic renal failure is the lack of vascular access due to venous thrombosis. This means that the transplant surgeon must have a detailed knowledge of the intra-abdominal venous system, and other alternative surgeries, at the time of performing the renal graft implant, in order to ensure a good venous drainage. PRESENTATION OF THE CASE: This article provides a case report regarding a patient with no vascular access and with surgical difficulties at the time of the kidney transplant, in whom a renal-portal venous drainage was performed with very good outcome. DISCUSION: Renal-portal venous drainage is a way to performe kidney transplant with good outcome. In Fundación Valle del Lili we have overcome the lack of vascular access in patients that need a renal transplant by new surgical technics that improve the patients quality of life and survival. CONCLUSION: We can conclude that new surgical alternatives exist for those patients with chronic renal failure that have no vascular access. These patients are a priority for kidney transplants and the surgeon must take in to account the need for a new surgical assessment.

13.
Xenotransplantation ; 22(1): 32-47, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25209710

RESUMO

BACKGROUND: Dysregulation of coagulation is considered a major barrier against successful pig organ xenotransplantation in non-human primates. Inflammation is known to promote activation of coagulation. The role of pro-inflammatory factors as well as the relationship between inflammation and activation of coagulation in xenograft recipients is poorly understood. METHODS: Baboons received kidney (n=3), heart (n=4), or artery patch (n=8) xenografts from α1,3-galactosyltransferase gene-knockout (GTKO) pigs or GTKO pigs additionally transgenic for human complement-regulatory protein CD46 (GTKO/CD46). Immunosuppression (IS) was based on either CTLA4Ig or anti-CD154 costimulation blockade. Three artery patch recipients did not receive IS. Pro-inflammatory cytokines, chemokines, and coagulation parameters were evaluated in the circulation after transplantation. In artery patch recipients, monocytes and dendritic cells (DC) were monitored in peripheral blood. Expression of tissue factor (TF) and CD40 on monocytes and DC were assessed by flow cytometry. C-reactive protein (C-RP) levels in the blood and C-RP deposition in xenografts as well as native organs were evaluated. Baboon and pig C-RP mRNA in heart and kidney xenografts were evaluated. RESULTS: In heart and kidney xenograft recipients, the levels of INFγ, TNF-α, IL-12, and IL-8 were not significantly higher after transplantation. However, MCP-1 and IL-6 levels were significantly higher after transplantation, particularly in kidney recipients. Elevated C-RP levels preceded activation of coagulation in heart and kidney recipients, where high levels of C-RP were maintained until the time of euthanasia in both heart and kidney recipients. In artery patch recipients, INFγ, TNF-α, IL-12, IL-8, and MCP-1 were elevated with no IS, while IL-6 was not. With IS, INFγ, TNF-α, IL-12, IL-8, and MCP-1 were reduced, but IL-6 was elevated. Elevated IL-6 levels were observed as early as 2 weeks in artery patch recipients. While IS was associated with reduced thrombin activation, fibrinogen and C-RP levels were increased when IS was given. There was a significant positive correlation between C-RP, IL-6, and fibrinogen levels. Additionally, absolute numbers of monocytes were significantly increased when IS was given, but not without IS. This was associated with increased CD40 and TF expression on CD14+ monocytes and lineage(neg) CD11c+ DC, with increased differentiation of the pro-inflammatory CD14+ CD11c+ monocyte population. At the time of euthanasia, C-RP deposition in kidney and heart xenografts, C-RP positive cells in artery patch xenograft and native lungs were detected. Finally, high levels of both pig and baboon C-RP mRNA were detected in heart and kidney xenografts. CONCLUSIONS: Inflammatory responses precede activation of coagulation after organ xenotransplantation. Early upregulation of C-RP and IL-6 levels may amplify activation of coagulation through upregulation of TF on innate immune cells. Prevention of systemic inflammation in xenograft recipients (SIXR) may be required to prevent dysregulation of coagulation and avoid excessive IS after xenotransplantation.


Assuntos
Coagulação Sanguínea , Xenoenxertos/patologia , Inflamação/etiologia , Complicações Pós-Operatórias/etiologia , Animais , Animais Geneticamente Modificados , Artérias/transplante , Fatores de Coagulação Sanguínea/análise , Proteína C-Reativa/biossíntese , Proteína C-Reativa/genética , Quimiocinas/sangue , Citocinas/sangue , Células Dendríticas/imunologia , Galactosiltransferases/deficiência , Galactosiltransferases/genética , Técnicas de Inativação de Genes , Transplante de Coração , Xenoenxertos/imunologia , Humanos , Imunossupressores , Inflamação/sangue , Inflamação/genética , Transplante de Rim , Proteína Cofatora de Membrana/genética , Proteína Cofatora de Membrana/imunologia , Monócitos/imunologia , Papio , Complicações Pós-Operatórias/sangue , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Sus scrofa , Suínos , Tromboplastina/biossíntese , Tromboplastina/genética
14.
Cell Transplant ; 22(12): 2335-44, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23336557

RESUMO

Currently, islet cells are transplanted into the liver via portal vein infusion. One disadvantage of this approach is that it is not possible to adequately biopsy the islets in the liver to assess for rejection. Islet transplantation (Tx) into the gastric submucosal space (GSMS) can be performed endoscopically and has the potential advantage of histological evaluation by endoscopic biopsy. The aim of this study was to determine whether a representative allograft sample could be obtained endoscopically. We performed islet Tx into the GSMS in nonimmunosuppressed pigs using simple endoscopic submucosal injection. Islets were transplanted at four sites. Endoscopic ultrasonography and biopsy of the transplanted islets at two sites by modified endoscopic submucosal dissection were carried out successfully in all pigs 5 days after islet Tx. Tissue obtained at both biopsy and necropsy (including full-thickness sections of the gastric wall around the sites of the remaining islets and biopsies) were examined by histology and immunohistochemistry to confirm the presence of the islet grafts and any features of rejection. Representative allograft sampling was successfully obtained from all biopsy sites. All biopsies included islets with insulin-positive staining. There was significant CD3(+) and CD68(+) cell infiltration in the islet masses obtained at biopsy and from sections taken at necropsy, with similar histopathological features. Endoscopic biopsy of islet allografts in the GSMS is feasible, provides accurate histopathological data, and would provide a significant advance if translated into clinical practice.


Assuntos
Transplante das Ilhotas Pancreáticas , Ilhotas Pancreáticas/patologia , Animais , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Complexo CD3/metabolismo , Endoscopia do Sistema Digestório , Endossonografia , Feminino , Mucosa Gástrica/cirurgia , Sobrevivência de Enxerto , Ilhotas Pancreáticas/diagnóstico por imagem , Ilhotas Pancreáticas/metabolismo , Necrose/metabolismo , Necrose/patologia , Suínos , Transplante Homólogo
15.
Transplantation ; 94(12): 1187-91, 2012 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-23128998

RESUMO

BACKGROUND: Large animals treated with immunosuppressive drugs for preclinical experiments of transplantation have increased risks of infection, which can be compounded by the induction of diabetes if islet transplantation is planned. METHODS: We report our experience with severe sepsis in two young cynomolgus monkeys and five pigs that were subjected to diabetes induction, immunosuppressive therapy, or islet allotransplantation. RESULTS: In two monkeys and five pigs, infection was associated with a syndrome of profound hypoglycemia accompanied by severe acidosis, which was resistant to treatment. We do not believe that this syndrome has been reported previously by others. CONCLUSIONS: Despite treatment, this syndrome complicated the interpretation of blood glucose readings as a measure of islet graft function and resulted in death or the need for euthanasia in all seven animals. We tentatively suggest that the syndrome may be related to the presence of microorganisms that metabolize glucose and produce lactate.


Assuntos
Acidose/imunologia , Diabetes Mellitus Experimental/imunologia , Hipoglicemia/imunologia , Imunossupressores/farmacologia , Transplante das Ilhotas Pancreáticas/imunologia , Sepse/imunologia , Acidose/metabolismo , Animais , Bactérias/metabolismo , Glicemia/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/cirurgia , Modelos Animais de Doenças , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/imunologia , Hipoglicemia/metabolismo , Transplante das Ilhotas Pancreáticas/efeitos adversos , Ácido Láctico/sangue , Macaca fascicularis , Sepse/metabolismo , Índice de Gravidade de Doença , Suínos , Síndrome , Transplante Homólogo
16.
Cell Transplant ; 21(8): 1791-802, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22776064

RESUMO

Currently, islet transplantation as a cell therapeutic option for type 1 diabetes occurs via islet injection into the portal vein. Direct contact between islets and blood is a pathophysiological "provocation" that results in the instant blood-mediated inflammatory reaction (IBMIR) and is associated with early islet loss. However, the nature of the various insults on the islets in the blood stream remains mostly unknown. To gain insight into the mechanisms, we utilized a simplified in vitro model in which islets were exposed to blood in different clinically relevant but increasingly challenging, autologous, allogeneic, and xenogeneic combinations. Irrespective of the blood type and species compatibility, islets triggered blood clotting. Islet damage was worse as islet, and blood compatibility diminished, with substantial islet injury after exposure of porcine islets to human blood. Islet damage involved membrane leakage, antibody deposition, complement activation, positive staining for the membrane attack complex, and mitochondrial dysfunction. Islet damage occurred even after exposure to plasma only, and specific complement inactivation and neutralization of IgM substantially prevented islet damage, indicating the importance of humoral immunity. Efficacious measures are needed to reduce this injury, especially in view of a potential clinical use of porcine islets to treat diabetes.


Assuntos
Imunidade Humoral , Ilhotas Pancreáticas/imunologia , Animais , Coagulação Sanguínea/imunologia , Peptídeo C/metabolismo , Membrana Celular/metabolismo , Ativação do Complemento/imunologia , Complexo de Ataque à Membrana do Sistema Complemento/metabolismo , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Ilhotas Pancreáticas/patologia , Mitocôndrias/metabolismo , Suínos
17.
Transpl Int ; 25(8): 882-96, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22642260

RESUMO

Upregulation of tissue factor (TF) expression on activated donor endothelial cells (ECs) triggered by the immune response (IR) has been considered the main initiator of consumptive coagulopathy (CC). In this study, we aimed to identify potential factors in the development of thrombocytopenia and CC after genetically engineered pig liver transplantation in baboons. Baboons received a liver from either an α1,3-galactosyltransferase gene-knockout (GTKO) pig (n = 1) or a GTKO pig transgenic for CD46 (n = 5) with immunosuppressive therapy. TF exposure on recipient platelets and peripheral blood mononuclear cell (PBMCs), activation of donor ECs, platelet and EC microparticles, and the IR were monitored. Profound thrombocytopenia and thrombin formation occurred within minutes of liver reperfusion. Within 2 h, circulating platelets and PBMCs expressed functional TF, with evidence of aggregation in the graft. Porcine ECs were negative for expression of P- and E-selectin, CD106, and TF. The measurable IR was minimal, and the severity and rapidity of thrombocytopenia were not alleviated by prior manipulation of the IR. We suggest that the development of thrombocytopenia/CC may be associated with TF exposure on recipient platelets and PBMCs (but possibly not with activation of donor ECs). Recipient TF appears to initiate thrombocytopenia/CC by a mechanism that may be independent of the IR.


Assuntos
Coagulação Intravascular Disseminada/imunologia , Trombocitopenia/imunologia , Tromboplastina/genética , Transplante Heterólogo/imunologia , Animais , Animais Geneticamente Modificados , Micropartículas Derivadas de Células/imunologia , Galactosiltransferases/imunologia , Papio/imunologia , Sus scrofa/imunologia
18.
Transplantation ; 93(8): 769-76, 2012 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-22441321

RESUMO

BACKGROUND: We set out to determine whether B-cell tolerance to A/B-incompatible alloantigens and pig xenoantigens could be achieved in infant baboons. METHODS: Artery patch grafts were implanted in the abdominal aorta in 3-month-old baboons using A/B-incompatible (AB-I) allografts or wild-type pig xenografts (pig). Group 1 (Gp1) (controls, n=6) received no immunosuppressive therapy (IS) and no graft. Gp2 (n=2) received an AB-I or pig graft but no IS. Gp3 received AB-I grafts+IS (Gp3A: n=2) or pig grafts+IS (Gp3B: n=2). IS consisted of ATG, anti-CD154mAb, and mycophenolate mofetil until age 8 to 12 months. Gp4 (n=2) received IS only but no graft. RESULTS: In Gp1, anti-A/B and cytotoxic anti-pig immunoglobulin-M increased steadily during the first year. Gp2 became sensitized to donor-specific AB-I or pig antigens within 2 weeks. Gp3 and Gp4 infants that received anti-CD154mAb made no or minimal anti-A/B and anti-pig antibodies while receiving IS. DISCUSSION: The production of natural anti-A/B and anti-pig antibodies was inhibited by IS with anti-CD154mAb, even in the absence of an allograft or xenograft, suggesting that natural antibodies may not be entirely T-cell independent. These data are in contrast to clinical experience with AB-I allotransplantation in infants, who cease producing only donor-specific antibodies.


Assuntos
Anticorpos/imunologia , Soro Antilinfocitário/uso terapêutico , Imunossupressores/uso terapêutico , Ácido Micofenólico/análogos & derivados , Linfócitos T/imunologia , Animais , Animais Recém-Nascidos , Antígenos/imunologia , Soro Antilinfocitário/imunologia , Aorta Abdominal/imunologia , Aorta Abdominal/cirurgia , Artérias/imunologia , Artérias/transplante , Ligante de CD40/imunologia , Tolerância Imunológica/imunologia , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Imunossupressores/imunologia , Ácido Micofenólico/imunologia , Ácido Micofenólico/uso terapêutico , Papio , Suínos , Transplante Heterólogo
19.
Inflamm Bowel Dis ; 18(7): 1325-32, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22294413

RESUMO

BACKGROUND: Collagenous colitis is a chronic inflammatory bowel disease of unknown etiology. It is fairly common in adult humans, but rare in infants, and has been associated with autoimmune disorders. METHODS: We report four infant baboons (age 7-12 months) that had received a transplant at 3 months of age and subsequent immunosuppressive therapy for periods of 4-10 months. All presented identical symptoms within a period of 4 weeks, including weight loss associated with chronic watery diarrhea that was unresponsive to standard antimicrobial treatment. RESULTS: Clinical chemistry evaluations were within normal ranges, viral causes were ruled out, and fecal and blood cultures were repeatedly negative. At necropsy, two infant baboons were found to have a form of collagenous colitis. In the remaining two baboons that had identical clinical features, immunosuppressive therapy was discontinued and treatment with budesonide was initiated. Both baboons recovered and remained well on no medication until the end of follow-up (24 months). CONCLUSIONS: Collagenous colitis has occasionally been reported in patients with organ transplants. It has been reported only once previously in baboons. The four cases reported here strongly suggest that 1) clinical features as well as histopathological findings of collagenous colitis in baboons are very similar to those in human patients; 2) it was associated with the immunocompromised state of the baboons, as two nonimmunosuppressed age-matched baboons in close proximity did not develop the condition; and 3) it may have had an infectious origin, as all four cases developed within a 4-week period of time.


Assuntos
Colite Colagenosa/etiologia , Colite Colagenosa/patologia , Diarreia/patologia , Imunossupressores/efeitos adversos , Animais , Animais Recém-Nascidos , Anti-Inflamatórios/uso terapêutico , Budesonida/uso terapêutico , Colite Colagenosa/imunologia , Diarreia/tratamento farmacológico , Diarreia/etiologia , Feminino , Humanos , Terapia de Imunossupressão , Masculino , Papio , Redução de Peso
20.
Am Surg ; 78(1): 20-5, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22273293

RESUMO

Complex liver trauma often presents major diagnostic and management problems. Current operative management is mainly centered on packing, damage control, and early utilization of interventional radiology for angiography and embolization. In this retrospective observational study of patients admitted to the Mediterranean Institute for Transplantation and Advanced Specialized Therapies, Palermo, Italy, from 1999 to 2010, we included patients that underwent hepatic resection for complex liver injuries (grade I to V according to the American Association for the Surgery of Trauma-Organ Injury Scale). Age, gender, mechanism of trauma, type of resection, surgical complications, length of hospital stay, and mortality were the variables analyzed. A total of 53 adult patients were admitted with liver injury and 29 underwent surgical treatment; the median age was 26.7 years. Mechanism was blunt in 52 patients. The overall morbidity was 30 per cent, morbidity related to liver resection was 15.3 per cent. Mortality was 2 per cent in the series of patients undergoing liver resection for complex hepatic injury, whereas in the nonoperative group, morbidity was 17 per cent and mortality 2 per cent. Liver resection should be considered a serious surgical option, as initial or delayed management, in patients with complex liver injury and can be accomplished with low mortality and liver-related morbidity when performed in specialized liver surgery/transplant centers.


Assuntos
Hepatectomia/métodos , Fígado/lesões , Fígado/cirurgia , Ferimentos não Penetrantes/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Hemorragia/prevenção & controle , Mortalidade Hospitalar , Humanos , Lactente , Itália/epidemiologia , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Radiografia Intervencionista , Estudos Retrospectivos , Resultado do Tratamento , Ferimentos não Penetrantes/mortalidade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA