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1.
Transplant Proc ; 53(2): 624-629, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33139038

RESUMO

BACKGROUND: The relationship between nutrition and liver disease is relevant for the outcome after surgery. Patients with liver cirrhosis characteristically show protein-energy malnutrition with decreased levels of branched-chain amino acids (BCAA) and increased levels of aromatic amino acids. MATERIALS AND METHODS: We conducted a prospective controlled clinical trial including 57 patients after liver transplantation or major liver resection surgery in order to test the effect of early postoperative nutrition on the outcome and nutrition profile of these patients. The test group received a dietetic program composed of ingredients naturally rich in BCAA (BCAA group), and the control group received standard hospital meals. Patient survival, liver function tests, subjective well-being, and a nutritional status including amino acid profiles were analyzed immediately and 14 days after major liver surgery (secondary end points). General health and well-being were assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (primary end point). RESULTS: In-depth analysis of amino acid profiles was performed for patients undergoing liver resection (n = 21) and liver transplantation (n = 36). Interestingly, amino acid profiles did not correlate with body mass index or the Model for End-Stage Liver Disease score. Patients scheduled for liver transplantation showed significantly lower levels of BCAA pretransplant compared to patients undergoing liver resection. Patients in the liver resection subgroup were more likely to benefit from the BCAA cuisine in terms of significantly higher food intake and subjective rating. The clinical liver function tests, however, did not show statistical difference between the BCAA group and the control group in the examination period of 14 days. CONCLUSION: Our specifically designed BCAA-enriched diet resulted in greater patient satisfaction and compliance with nutrition. A larger trial or longer-term follow-up may be required to identify an effect on survival, recovery, surgical complications, protein profiles, and amino acid profiles.


Assuntos
Aminoácidos de Cadeia Ramificada/uso terapêutico , Hepatopatias/dietoterapia , Hepatopatias/cirurgia , Transplante de Fígado , Aminoácidos de Cadeia Ramificada/sangue , Feminino , Hepatectomia/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Estudos Prospectivos
2.
Am J Transplant ; 10(4): 846-851, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20420640

RESUMO

Thrombotic complications following pancreas transplantation are still the most common cause of nonimmunologic graft loss. The aim of this study was to analyze pancreatic graft function after partial arterial graft thrombosis and the investigation of the pancreatic arterial anatomy with regard to intraparenchymal anastomoses. We retrospectively analyzed the data for 175 consecutive pancreas transplants performed between January 2002 and October 2007. Selective Y-graft angiography was performed in 10 and rubber-milk injection in 5 fresh pancreas specimens. Thrombosis of one leg of the Y-graft was diagnosed in 18 (10.3%) patients. Only one of these patients with thrombosis of the splenic artery required exogenous insulin. Sufficient graft perfusion was demonstrated in all of the remaining grafts. One graft was lost due to acute rejection. In all specimens angiography showed an excellent perfusion of the pancreaticoduodenal arcade, even after selective cannulation of the splenic artery. Arterial collaterals between the gastroduodenal, splenic artery and the superior mesenteric artery were demonstrated. Our results demonstrate that global perfusion of the pancreatic graft and sufficient graft function is sustained after the thrombotic occlusion of one branch of the Y-graft by a complex system of intraparenchymal anastomoses. These anatomical findings may have consequences for resection strategies in pancreas surgery.


Assuntos
Anastomose Cirúrgica , Sobrevivência de Enxerto , Transplante de Pâncreas , Baço/patologia , Trombose/complicações , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
3.
Am J Transplant ; 10(10): 2231-40, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20883557

RESUMO

Depletion of the nitric oxide synthase cofactor tetrahydrobiopterin (H4B) during ischemia and reperfusion is associated with severe graft pancreatitis. Since clinically feasible approaches to prevent ischemia reperfusion injury (IRI) by H4B-substitution are missing we investigated its therapeutic potential in a murine pancreas transplantation model using different treatment regimens. Grafts were subjected to 16 h cold ischemia time (CIT) and different treatment regimens: no treatment, 160 µM H4B to perfusion solution, H4B 50 mg/kg prior to reperfusion and H4B 50 mg/kg before recovery of organs. Nontransplanted animals served as controls. Recipient survival and endocrine graft function were assessed. Graft microcirculation was analyzed 2 h after reperfusion by intravital fluorescence microscopy. Parenchymal damage was assessed by histology and nitrotyrosine immunohistochemistry, H4B tissue levels by high pressure liquid chromatography (HPLC). Compared to nontransplanted controls prolonged CIT resulted in significant microcirculatory deterioration. Different efficacy according to route and timing of administration could be observed. Only donor pretreatment with H4B resulted in almost completely abrogated IRI-related damage showing graft microcirculation comparable to nontransplanted controls and restored intragraft H4B levels, resulting in significant reduction of parenchymal damage (p < 0.002) and improved survival and endocrine function (p = 0.0002 each). H4B donor pretreatment abrogates ischemia-induced parenchymal damage and represents a promising strategy to prevent IRI following pancreas transplantation.


Assuntos
Biopterinas/análogos & derivados , Transplante de Pâncreas/métodos , Traumatismo por Reperfusão/prevenção & controle , Doadores de Tecidos , Animais , Biopterinas/uso terapêutico , Isquemia Fria , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microcirculação , Modelos Animais , Pâncreas/irrigação sanguínea , Pâncreas/patologia , Transplante de Pâncreas/fisiologia , Ácido Peroxinitroso/biossíntese , Transplante Isogênico , Tirosina/análogos & derivados , Tirosina/biossíntese
4.
Am J Transplant ; 10(5): 1200-9, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20353468

RESUMO

Skin rejection remains a major hurdle in reconstructive transplantation. We investigated molecular markers of skin rejection with particular attention to lymphocyte trafficking. Skin biopsies (n = 174) from five human hand transplant recipients were analyzed for rejection, characteristics of the infiltrate and lymphocytic adhesion markers. The cellular infiltrate predominantly comprised CD3+ T cells. CD68, Foxp3 and indoleamine 2, 3-dioxygenase expression and the CD4/CD8 increased with severity of rejection. Lymphocyte adhesion markers were upregulated upon rejection, intercellular adhesion molecule-1 and E-selectin correlated best with severity of rejection. Guided by the findings, a specific E- and P-selectin inhibitor was investigated for its effect on skin rejection in a rat hind limb allotransplant model. While efomycine M (weekly s.c. injection into the graft) alone had no effect, long-term allograft survival was achieved when combined with antithymocyte globulin and tacrolimus (control group without efomycine M rejected at postoperative day [POD] 61 +/- 1). Upregulation of lymphocyte trafficking markers correlates with severity of skin rejection and time after transplantation in human hand transplantation. Blocking E- and P-selectin in the skin holds potential to significantly prolong limb allograft survival.


Assuntos
Selectina E/imunologia , Molécula 1 de Adesão Intercelular/imunologia , Selectina-P/imunologia , Animais , Antígenos CD , Antígenos de Diferenciação Mielomonocítica , Soro Antilinfocitário/imunologia , Biomarcadores , Biópsia , Humanos , Linfócitos/imunologia , Linfócitos/patologia , Masculino , Ratos , Ratos Endogâmicos BN , Ratos Endogâmicos Lew , Pele/imunologia , Pele/patologia , Tacrolimo/imunologia , Fatores de Tempo
5.
Colorectal Dis ; 12(5): 452-8, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-19222523

RESUMO

OBJECTIVE: Modern haemorrhoidectomy techniques aim to interrupt arterial blood supply to the hypertrophied piles. The aim of this study was to investigate morphological and physiological alterations in the terminal branches of the superior rectal artery (SRA) in patients with haemorrhoidal disease treated by stapled haemorrhoidopexy (SH) using noninvasive transperineal ultrasound. METHOD: Thirty-seven consecutive patients (14 women, 23 men; median age 52, range 30-77 years) who underwent SH for treatment of grade III haemorrhoids were scanned by transperineal colour Doppler ultrasound at baseline, 4 weeks and 3 months postoperatively. Seventeen healthy volunteers served as the control group (nine women, eight men; median age 24, range 18-72 years). Calibre and arterial flow velocity (AFV) of the terminal branches of the SRA were measured. RESULTS: Baseline measurements significantly differed between patients and the control group (median calibre 2, range 0.9-3.6 mm, vs 1, range 0.6-1.2 mm, and median AFV 24, range 10-65 cm/s, vs 12, range 5-21 cm/s, P < 0.0001). Postoperative follow-up showed no significant alterations in the physiological parameters. Patients with a higher recurrence rate of haemorrhoidal disease had higher baseline AFV values. CONCLUSION: Stapled haemorrhoidopexy does not reduce arterial inflow in the feeding vessels of the anorectal vascular plexus. Preoperative ultrasound may serve as a tool for assessing vascularization status in haemorrhoidal disease and is useful in deciding whether patients should undergo SH or, for individuals with high AFV, whether conventional haemorrhoidectomy might be the better choice.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório , Hemorroidas/cirurgia , Reto/irrigação sanguínea , Grampeamento Cirúrgico , Adolescente , Adulto , Idoso , Feminino , Hemorroidas/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Ultrassonografia Doppler em Cores , Adulto Jovem
6.
Colorectal Dis ; 12(7 Online): e121-7, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19341401

RESUMO

BACKGROUND: Anal abscesses are commonly associated with fistulas-in-ano and are usually polymicrobial in nature, with gram-negative rods and anaerobes being the most prevalent isolates. Group Milleri Streptococci (GMS) comprise a heterogeneous group of cocci, which are capable of causing severe purulent infection with a high recurrence rate. METHOD: All anorectal infections caused by GMS, which were identified at our centre during a 4-year period were retrospectively analysed. The 18 patients with GMS-positive anorectal abscesses were matched with 36 GMS-negative anorectal abscesses to identify outcome characteristics of this clinical entity. RESULTS: During the study period, 358 patients underwent surgical treatment for anal infections; GMS were isolated in 46 individuals (13%) including 18 perianal abscesses, 11 pilonidal sinuses, eight fistulae in and nine miscellaneous infections. Seventy-two per cent of perianal GMS infections were polymicrobial with E. coli and Bacteroides fragilis being the predominant second bacteria. Nine patients (20%) developed recurrent abscesses and fistulae-in-ano and underwent additional surgical interventions with resolution at follow-up. Additional antibiotic treatment was administered in 10 patients with complex anal infections. Matched pair analysis revealed that GMS-positive perianal abscesses were more commonly polymicrobial, and that the recurrence rate was higher (55.6% GMS-positive and 22.2% GMS-negative patients, P = 0.017). CONCLUSIONS: Our data confirm the propensity of GMS to form deep and recurrent abscesses with a higher recurrence rate than non-GMS infections. First-line treatment includes surgical drainage, and antibiotic treatment may be useful in selected patients.


Assuntos
Antibacterianos/uso terapêutico , Drenagem/métodos , Proctite/microbiologia , Infecções Estreptocócicas/microbiologia , Streptococcus milleri (Grupo)/isolamento & purificação , Abscesso/epidemiologia , Abscesso/microbiologia , Abscesso/cirurgia , Adolescente , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Proctite/epidemiologia , Proctite/cirurgia , Estudos Retrospectivos , Prevenção Secundária , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/cirurgia , Adulto Jovem
7.
Transplant Proc ; 41(2): 517-20, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19328916

RESUMO

BACKGROUND: Composite tissue allograft (CTA) recipients require high level of immunosuppression and, therefore, are at significant risk to acquire opportunistic infections. PATIENTS AND METHODS: A review of all serious infectious complications in the 3 CTA recipients from the Innsbruck Medical University was performed. RESULTS: The most common infection was cytomegalovirus (CMV)-associated disease, which developed in all 3 individuals. The CMV match was CMV-positive donor/CMV-negative recipient in the first case and CMV-positive donor/CMV-positive recipient in the other 2. The first 2 patients developed complicated CMV infections despite ganciclovir (GCV) prophylaxis and required treatment with anti-CMV hyperimmunoglobulin, foscarnet, and cidofovir to control infection. The third patient had a mild course of CMV disease after withdrawel of prophylaxis, which was successfully treated with ValGCV. Whereas no major additional infections were observed in the first and third case, the second patient, who experienced multiple steroid-resistent rejections, experienced a variaty of additional infections, including 1 episode of Clostridium difficile-associated colitis (CDAC), a soft tissue infection with Alternaria alternata and an infection with human papilloma virus (HPV), which extensively involved both transplanted forearms. CDAC was successfully treated with metronidazole, Alternaria alternata with liposomal amphotericin B, and itraconazole and HPV lesions with topical cidofovir. CONCLUSION: Rare and difficult to treat infections must be expected in CTA recipients, in particular when donor-derived viruses are introduced in naïve recipients and when excessive immunosuppression is required. Meticulous infectious screening and prophylaxis are warranted in these high-risk patients.


Assuntos
Infecções por Citomegalovirus/diagnóstico , Transplante de Mão , Infecção da Ferida Cirúrgica/diagnóstico , Transplante Homólogo/efeitos adversos , Adulto , Antibacterianos/uso terapêutico , Antibioticoprofilaxia , Antivirais/uso terapêutico , Clostridioides difficile , Infecções por Citomegalovirus/tratamento farmacológico , Enterocolite Pseudomembranosa/diagnóstico , Enterocolite Pseudomembranosa/tratamento farmacológico , Lateralidade Funcional , Teste de Histocompatibilidade , Humanos , Imunossupressores/uso terapêutico , Infecção da Ferida Cirúrgica/tratamento farmacológico
8.
Transplant Proc ; 41(2): 472-5, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19328906

RESUMO

Avoidance or at least minimization of maintenance immunosuppression represents the key step for promoting wider applicability of reconstructive transplantation. Understanding the mechanisms of composite tissue allograft rejection is essential in working toward that goal. We herein review the current knowledge on acute rejection in reconstructive transplantation and discuss findings in the light of novel immunosuppressive and immunomodulatory strategies.


Assuntos
Transplante de Mão , Terapia de Imunossupressão/métodos , Transplante Homólogo/história , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/história , História do Século XXI , Humanos , Terapia de Imunossupressão/história , Imunossupressores/uso terapêutico , Anormalidades Musculoesqueléticas/cirurgia , Procedimentos de Cirurgia Plástica/história , Transplante Homólogo/imunologia
9.
Transplant Proc ; 41(2): 509-12, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19328914

RESUMO

Human hand transplantation is complicated by skin rejection. To better define the characteristics of infiltrating cells, biopsies from human hand transplants have been investigated for expression of Foxp3 and indoleamine 2,3-dioxygenase (IDO), a key regulatory enzyme to induce T-lymphocyte unresponsiveness. A total of 104 skin biopsies taken from three bilateral hand transplant recipients over 6 years posttransplant were assessed by hematoxylin-eosin histology (graded 1-4b) and immunohistochemistry for IDO and Foxp3 according to a three-grade classification and correlated with the grade of rejection as well as time after transplantation. Overall, rejection ranged between grades 0 and 4a with an average score of 0.94. IDO was expressed in the endothelium independent of rejection. Upon rejection, IDO staining within the cellular infiltrate was significantly increased. Foxp3 in regulatory T cells was mainly found in samples undergoing severe rejection. Expression of IDO and Foxp3 compared well to each other, although the overall expression of Foxp3 was lower when compared to IDO. An increased expression of IDO as well as Foxp3 during rejection late after transplantation was observed. Characteristics of the cellular infiltrate indicate tolerogenic properties of a proportion of the cells and therefore a tendency toward self-limitation of the alloimmune response during skin rejection after hand transplantation.


Assuntos
Fatores de Transcrição Forkhead/metabolismo , Transplante de Mão , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Transplante de Pele/patologia , Biomarcadores/metabolismo , Rejeição de Enxerto/imunologia , Humanos , Imuno-Histoquímica , Imunossupressores/uso terapêutico , Linfócitos T Reguladores/imunologia , Transplante Homólogo/imunologia , Transplante Homólogo/patologia
10.
Transplant Proc ; 41(2): 499-502, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19328912

RESUMO

Minimization of immunosuppression has become the key effort in solid organ transplantation. Alemtuzumab, the humanized CD-52 monoclonal antibody, is an effective depleting agent increasingly used in transplantation trials. In this article, we summarize the current experience with alemtuzumab use in hand transplantation and discuss its role in current and future approaches toward minimization of maintenance immunosuppression in reconstructive transplantation.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Anticorpos Antineoplásicos/uso terapêutico , Braço/transplante , Transplante de Mão , Terapia de Imunossupressão/métodos , Procedimentos de Cirurgia Plástica/métodos , Imunologia de Transplantes , Alemtuzumab , Amputação Cirúrgica , Anticorpos Monoclonais Humanizados , Áustria , Feminino , Antebraço/cirurgia , Lateralidade Funcional , Teste de Histocompatibilidade , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos de Cirurgia Plástica/psicologia , Espanha , Transplante Homólogo/imunologia , Transplante Homólogo/psicologia , Estados Unidos , Adulto Jovem
11.
Transplant Proc ; 41(2): 491-4, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19328910

RESUMO

We herein provide an update on two bilateral hand and one bilateral forearm transplants with emphasis on immunosuppression (IS), function, morphology, and graft vascular changes at 8 years and 2 years after bilateral hand and 5 years after bilateral forearm transplantation. Between March 2000 and May 2006, three patients underwent bilateral hand or forearm transplantation at our institution. Following induction therapy with antithymocyte globulin (ATG) (n = 2) or alemtuzumab (n = 1), tacrolimus, prednisolone +/- mycophenolate mofetil (MMF) were given for maintenance IS. Later, tacrolimus (n = 1) or MMF (n = 1) was replaced by sirolimus/everolimus for long-term IS. Clinical follow-ups with evaluation of hand function, skin biopsies, X-ray, ultrasound, angiography, computed tomography angiography, electrophysiological studies, and somatosensory evoked potentials were performed at regular intervals. Three, six, and three rejection episodes were successfully treated with bolused steroids, anti-CD25 or anti-CD52 antibodies. Subsequently, skin histology remained normal without any evidence of chronic rejection. Hand function continuously improved during the first 3 years and since then remained stable with minor improvements. Investigation of hand arteries revealed no signs of occlusion or stenosis. Motor and intrinsic hand muscle function continues to improve in all patients. Protective sensation was observed in all patients; however, discriminative sensation was only accomplished after hand but not forearm transplantation. No life-threatening adverse events occurred. Despite immunologic challenging postoperative courses, patients are now free of rejection with moderate levels of IS and good functional results. No signs indicating chronic rejection have been encountered.


Assuntos
Braço/transplante , Transplante de Mão , Imunossupressores/uso terapêutico , Acidentes , Adulto , Antivirais/uso terapêutico , Braço/fisiologia , Artérias/transplante , Áustria , Meios de Comunicação , Infecções por Citomegalovirus/tratamento farmacológico , Quimioterapia Combinada , Seguimentos , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/imunologia , Mãos/fisiologia , Humanos , Terapia de Imunossupressão/efeitos adversos , Terapia de Imunossupressão/métodos , Masculino , Pessoa de Meia-Idade , Jornais como Assunto , Transplante Homólogo/imunologia
12.
Br J Cancer ; 99(8): 1290-5, 2008 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-18813308

RESUMO

Pancreatic cancer is one of the most devastating human malignancies. Despite considerable research efforts, it remains resistant to almost all available treatment regimens. The human trophoblast cell-surface antigen, TROP2, was found to be strongly expressed in a variety of human epithelial cancers, correlating with aggressiveness and poor prognosis. TROP2 antigen expression was investigated retrospectively by immunohistochemistry in paraffin-embedded primary tumour tissue samples from a series (n=197) of consecutive patients with pancreatic adenocarcinoma. Survival was calculated using Kaplan-Meier curves. Parameters found to be of prognostic significance in univariate analysis were verified in a multivariate Cox regression model. TROP2 overexpression was observed in 109 (55%) of 197 pancreatic cancer patients and was significantly associated with decreased overall survival (P<0.01). By univariate analysis, TROP2 overexpression was found to correlate with the presence of lymph node metastasis (P=0.04) and tumour grade (P=0.01). Furthermore, in the subgroup of patients treated surgically with curative intent, TROP2 overexpression significantly correlated with poor progression-free survival (P<0.01). Multivariate analyses revealed TROP2 to be an independent prognosticator. These findings suggest for the first time that TROP2 could be a novel prognostic biomarker for pancreatic cancer. Targeting TROP2 might be a useful treatment approach for patients with pancreatic cancer overexpressing this cell-surface marker.


Assuntos
Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidade , Antígenos de Neoplasias/biossíntese , Moléculas de Adesão Celular/biossíntese , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/patologia , Prognóstico , Estudos Retrospectivos
13.
Am J Transplant ; 8(7): 1480-5, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18510632

RESUMO

The lymphocyte-depleting antibody alemtuzumab was evaluated in a prospective randomized multicenter trial in deceased donor kidney transplantation. The 65 patients in the study group received induction with alemtuzumab followed by delayed tacrolimus monotherapy, while the 66 patients in the control group were started on tacrolimus in combination with mycophenolate mofetil and steroids. Tacrolimus levels of 8-12 ng/mL for the first 6 months and 5-8 ng/mL thereafter were aimed for in both groups. At 12 months the biopsy-proven rejection rate was 20% in the study group and 32% in the control group (p = 0.09). Patient survival at 1 year was 98% for both groups. Graft survival was 96% for the study group versus 90% for the control group (p = 0.18). Graft function was identical in both groups. Adverse events were similar in both groups apart for more CMV infections in the study group. At the end of the first year 82% of the patients in the study group were steroid-free and 71% continued on tacrolimus monotherapy. These results suggest that alemtuzumab induction together with tacrolimus monotherapy is at least as efficient in renal transplantation as is a tacrolimus-based triple-drug regimen with a similar safety profile but more CMV infections.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Anticorpos Antineoplásicos/uso terapêutico , Rejeição de Enxerto/tratamento farmacológico , Imunossupressores/uso terapêutico , Transplante de Rim , Tacrolimo/uso terapêutico , Adolescente , Adulto , Idoso , Alemtuzumab , Anticorpos Monoclonais Humanizados , Quimioterapia Combinada , Feminino , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapêutico , Resultado do Tratamento
14.
Am J Transplant ; 8(4): 773-82, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18294346

RESUMO

We investigated the role of secretory leukocyte protease inhibitor (SLPI) in ischemia/reperfusion injury in cardiac transplantation. SLPI-/- mouse hearts and wild-type (WT) controls were transplanted immediately or after 10 h of cold ischemia (CI). Recombinant SLPI (rSLPI) was added to the preservation solution or given systemically. After evaluation of myocardial performance, grafts were investigated for histology, SLPI, TNF-alpha, TGF-beta, NF-kappaB and protease expression at indicated time points. Early myocardial contraction was profoundly impaired in SLPI-/- hearts exposed to CI and associated with high intra-graft protease expression. Systemic administration of rSLPI had no effect, however, when SLPI was added to the preservation solution, myocardial contraction was restored to normal. At 10 days, inflammation, myocyte vacuolization and necrosis were significantly more severe in SLPI-/- hearts. SLPI gene expression was detected in WT mice at 12 and 24 h and was significantly higher after CI. SLPI protein was observed at 24 h and 10 days. High intra-graft concentrations of SLPI after administration of rSLPI were inversely correlated with protease levels early and TGF-beta expression late after reperfusion. SLPI plays a crucial role in early myocardial performance and postischemic inflammation after cardiac transplantation. A dual inhibitory effect on protease and TGF-beta expression might be the underlying mechanism.


Assuntos
Transplante de Coração/fisiologia , Inibidor Secretado de Peptidases Leucocitárias/deficiência , Inibidor Secretado de Peptidases Leucocitárias/uso terapêutico , Animais , Western Blotting , Ensaio de Imunoadsorção Enzimática , Transplante de Coração/métodos , Transplante de Coração/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Contração Miocárdica , Proteínas Recombinantes/uso terapêutico , Traumatismo por Reperfusão , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Inibidor Secretado de Peptidases Leucocitárias/genética , Fator de Crescimento Transformador beta/fisiologia , Transplante Isogênico
15.
Am J Transplant ; 8(3): 688-96, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18261182

RESUMO

Skin rejection after hand transplantation is characterized by a maculopapular erythematous rash that may be diffuse, patchy or focal, and distributed over forearms and dorsum of the hands. This 'classical' pattern of rejection usually spares the skin of the palm and does not affect the nails. Herein, we report the experience on four cases presenting with an 'atypical' pattern of rejection that is novel in involving the palmar skin and the nails. All patients were young and exposed to repetitive and persistent mechanical stress of the palm. Characteristic features of rejection included a desquamative rash associated with dry skin, red papules, scaling and lichenification localized to the palm. Skin lesions were associated with nail dystrophy, degeneration, deformation or loss. Histology of the skin and nail bed revealed a lymphocytic infiltrate with predominance of T cells (CD3+, CD4+ and CD8+), with small numbers of B cells (CD20+ and CD79a+) and a low number of Forkhead transcription factor 3 (FOXP3)-positive cells in one patient. The lesions persisted over weeks to months, responded poorly to steroid treatment and were managed with antithymocyte globulin (ATG; Thymoglobulin, Genzyme, Cambridge, MA), alemtuzumab and/or intensified maintenance immunosuppression.


Assuntos
Rejeição de Enxerto/patologia , Transplante de Mão , Pele/patologia , Adulto , Antígenos CD/análise , Linfócitos B/imunologia , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/tratamento farmacológico , Humanos , Terapia de Imunossupressão , Masculino , Pele/imunologia , Linfócitos T/imunologia
16.
Am J Transplant ; 8(1): 50-7, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17973969

RESUMO

Renal transplantation faces challenges: the organ shortage resulting in extended waiting times and an aging population resulting in death with a functioning graft. The Eurotransplant Senior Program (ESP) allocates kidneys within a narrow geographic area from donors aged >/=65 years to recipients >/=65 years regardless of HLA. This analysis investigates the impact of the ESP on waiting time, graft and patient survival. The ESP group (n = 1406, old to old) was compared to two groups allocated via the Eurotransplant Kidney Allocation System (ETKAS) with either similar donor age (old to any [O/A], donor age >/=65, n = 446) or recipient age (any to old, [A/O], recipient age 60-64, n = 1687). All patients were transplanted between 1999 and 2004. Since initiation of the ESP (1999), availability of elderly donors doubled and waiting time for ESP patients decreased. Local allocation led to shorter cold ischemia time (11.9 vs. >17.0 h, p < 0.001) and less delayed graft function (DGF, ESP 29.7% vs. O/A 36.2%, p = 0.047) but 5-10% higher rejection rates. Graft and patient survival were not negatively affected by the ESP allocation when compared to the standard allocation. The ESP age matching of elderly donors and recipients is an effective allocation system for organs from elderly donors.


Assuntos
Transplante de Rim , Doadores de Tecidos , Obtenção de Tecidos e Órgãos , Fatores Etários , Idoso , Europa (Continente) , Feminino , Seguimentos , Sobrevivência de Enxerto , Teste de Histocompatibilidade/estatística & dados numéricos , Humanos , Transplante de Rim/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Obtenção de Tecidos e Órgãos/estatística & dados numéricos , Listas de Espera
17.
Acta Chir Belg ; 108(6): 673-8, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-19241916

RESUMO

The Immunosuppression in Pancreas Transplantation was historically based on the fact that the pancreas is an extremely immunogenic organ. Quadruple drug therapy with polyclonal or monoclonal antibodies induction was the mainstay therapy since the introduction of Cyclosporine A. In the modern era of Immunosuppression, Mycophenolate Mofetil replaced Azathioprine while Tacrolimus-another potent calcineurin inhibitor-had-and still has-a difficult challenge to replaced Cyclosporine A, due to its potential diabetogenic effect. Thanks to the first two EuroSPK studies which prospectively tried to answer several questions in that field. But, the future challenge will be in understanding the impact of innate immunity and ischemic reperfusion injuries on the long-term graft function. Hopefully, new drugs will be available and tested to block unspecific deleterious reactions to attenuate the proinflammatory response. It will be the aim of the third Euro SPK Study.


Assuntos
Terapia de Imunossupressão , Transplante de Pâncreas/imunologia , Bélgica , Proteína C-Reativa/análise , Ensaios Clínicos como Assunto , Rejeição de Enxerto/prevenção & controle , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico
18.
Transplant Proc ; 50(10): 3199-3203, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30577185

RESUMO

BACKGROUND: The primary objective in living donor kidney transplantation is donor safety. In laparoscopic living donor nephrectomy, most centers prefer the left kidney for donation given the shorter renal vein, higher rate of thromboses, and more difficult surgical procedure for right kidney retrieval. The goal of this study was to demonstrate the feasibility of a hybrid technique using a Satinsky clamp in right-sided living donor nephrectomy to obtain maximal renal vein and to compare the outcome with standard left-sided laparoscopic donor nephrectomies. MATERIAL AND METHODS: Between 2005 and 2013, 77 patients underwent a left (group L) and 54 a right (group R) living donor nephrectomy. In group R, after laparoscopic dissection and mobilization of the right kidney, two 12-mm trocar incisions in the right upper quadrant were connected in a 5-7 cm subcostal incision. The caval vein was partially clamped under direct vision prior to dissection of the renal vein. The venotomy was then closed with a running 4-0 Prolene suture. The two groups were compared with regard to surgical complications, graft function, and graft survival. RESULTS: Using this technique, no significant difference with regard to complications or graft function was observed. Serum creatinine at discharge in donor group L was 1.23 (±0.43) mg/dL and in donor group R 1.21 (±0.37) mg/dL (P = .71). Graft survival at one year was 100% in both groups. CONCLUSION: Open management of the renal vein is a safe alternative in laparoscopic right-sided donor nephrectomy and ensures maximal length of the vein.


Assuntos
Doadores Vivos , Nefrectomia/métodos , Veias Renais/cirurgia , Coleta de Tecidos e Órgãos/métodos , Adulto , Feminino , Humanos , Transplante de Rim/métodos , Laparoscopia/instrumentação , Laparoscopia/métodos , Masculino , Pessoa de Meia-Idade , Nefrectomia/instrumentação , Coleta de Tecidos e Órgãos/instrumentação
20.
Clin Nephrol ; 68(5): 330-4, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18044267

RESUMO

Preemptive simultaneous kidney-pancreas transplantation (SKPT) was performed in two patients with Type 1 diabetes and nephrotic syndrome due to diabetic nephropathy, although the native kidneys exhibited near-normal function. Before and 3 months as well as 12 months after SKPT S-creatinine, creatinine clearance (Cr-Cl) and urinary protein excretion were measured. Additionally, 99mTC scintigraphic examinations of the kidneys were performed 3 and 12 months after SKPT. Thereby, the injected 99mTC activities were assessed in the kidney graft as well as in the patient's native kidneys. Aim of the study was to find out the impact of successful SKPT on proteinuria and further functioning of the patient's own kidneys after transplantation. Indication for pancreas transplantation was severe diabetic autonomic neuropathy and Brittle diabetes, respectively. In Patient 1, we registered 3 months after SKPT a near-normal protein excretion of mean 0.20 g/24-h urine at a Cr-Cl of 82 ml/ min. The scintigraphic examinations showed 60% of the radioactivity in the kidney graft and 40% in the patient's own kidneys (22% right and 18% left). Data 1 year after SKPT were: mean protein excretion 0.28 g/24-h urine, Cr-Cl 78 ml/min and in the scan, furthermore, 30% of the activity in the patient's native kidneys (16% right and 14% left). In Patient 2 after 3 months we obtained a mean protein excretion of 0.18 g/24-h urine at a Cr-Cl of 80 ml/min. Scintigram of the kidneys: 58% of the injected activity were measured in the kidney graft and 42% in the patient's own kidneys (22% right and 20% left). After 12 months of SKPT we measured a mean protein of 0.26 g/24-h urine and Cr-Cl 78 ml/min. Scintigram of the kidneys: 36% of the activity was in the patient's native kidneys (18% right and left). We conclude that in diabetic patients with nephrotic syndrome and near-normal function of the native kidneys SKPT leads to rapid and nearly complete diminution of proteinuria although the residual function of the patient's native kidneys was about 40% at 3 months after transplantation and slightly lower at 12 months after SKPT.


Assuntos
Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/fisiopatologia , Transplante de Rim , Transplante de Pâncreas , Proteinúria/complicações , Adulto , Feminino , Taxa de Filtração Glomerular , Humanos
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