RESUMO
ABO-incompatible kidney transplantation has become a popular alternative to kidney transplantation in Japan because of the severe shortage of cadaveric donors. In our institution, 21 cases of ABO-incompatible kidney transplantation were performed from April 2004, to October 2007. Recipient age was 42.8 +/- 14.5 years old; there were 9 men and 12 women. Duration of hemodialysis was 1,914 +/- 2,343 days. Donor operation was performed using a complete laparoscopic procedure. Recipient's splenectomy was performed using a hand-assisted laparoscopic procedure and kidney transplantation was performed with a standard method using an extraperitoneal approach. Pretransplant immunosuppressive protocol includes an administration of mycophenolate mofetil, tacrolimus, predonisolone, splenectomy, double filtration plasmapheresis (DFPP), and plasma exchange (PE). All patients showed an immediate graft function and their serum creatinine levels promptly decreased to 1.48 +/- 0.99 mg/dL on day 7 and 1.21 +/- 0.72 mg/dL on day 30. Both immunoglobulin (Ig)M and IgG titers were maintained at much lower levels for 7 days after transplantation in all patients. Cytomegalovirus antigenemia was observed in 11 patients (52.4%). One patient (4.8%) developed a Pneumocystis Carinii pneumonia and the formation of lymphocele was observed in one patient (4.8%). Total patient survival at 3 years was 95.2%, and graft survival at 3 years was 90.5%, which were almost equal to those in the patients who underwent ABO-matched, compatible kidney transplantation.
Assuntos
Sistema ABO de Grupos Sanguíneos/imunologia , Incompatibilidade de Grupos Sanguíneos , Sobrevivência de Enxerto/imunologia , Falência Renal Crônica/cirurgia , Transplante de Rim/imunologia , Cadáver , Humanos , Isoanticorpos/sangue , Transplante de Rim/mortalidade , Doadores Vivos , Estudos Retrospectivos , Análise de Sobrevida , Doadores de Tecidos , Resultado do TratamentoRESUMO
Reversible posterior leukoencephalopathy syndrome (RPLS) is one of the important side effects of calcineurin inhibitors (CNIs). Magnetic resonance imaging (MRI) of the brain is useful for the diagnosis of RPLS, showing the edema primarily in the cortex and subcortical white matter of the posterior brain regions. Interruption of CNIs is essential for the treatment of patients with RPLS. Herein we have described 2 cases (1.7%) of RPLS induced by CNIs after kidney transplantation. The first case was a 56-year-old man with chronic renal failure due to diabetic nephropathy who received a living-related kidney transplantation in 2006. Initial immunosuppressive therapy consisted of cyclosporine, mycophenolate mofetil (MMF), prednisolone, and basiliximab. Four months after transplantation, he developed unconsciousness and paralysis. The second case was a 24-year-old woman with end-stage renal disease due to Alport syndrome who received an ABO-incompatible living-related kidney transplantation. Initial immunosuppressive therapy consisted of tacrolimus, MMF, prednisolone, and basiliximab. On postoperative day 3, she developed convulsions and unconsciousness. In both patients, RPLS was diagnosed with neurological symptoms and MRI findings at early stage of the disease, and they recovered rapidly from the disease by the interruption of CNIs. Our data demonstrated that early diagnosis and immediate interruption of CNIs were essential for the treatment of RPLS after kidney transplantation.
Assuntos
Inibidores de Calcineurina , Imunossupressores/efeitos adversos , Transplante de Rim/imunologia , Ácido Micofenólico/análogos & derivados , Síndrome da Leucoencefalopatia Posterior/induzido quimicamente , Adulto , Encéfalo/patologia , Feminino , Humanos , Falência Renal Crônica/cirurgia , Doadores Vivos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/efeitos adversos , Nefrite Hereditária/cirurgia , Síndrome da Leucoencefalopatia Posterior/patologiaRESUMO
We performed the first case of simultaneous pancreas and kidney transplantation from a living donor (LDSPK) in 2004. We examined the quality of life (QOL) of performed 6 recipients and 5 donors among 8 LDSPK from 2004 to 2007 at our institution using Short Form 36. All recipients achieved insulin and hemodialysis independence after LDSPK with positive serum C-peptide levels. Before LDSPK, all scores of the 8 specific domains of the recipients were low (28.2 +/- 10.6), indicating extremely poor QOL. Both the Physical and the Mental Component Summary Scores (PCS/MCS) quickly increased after LDSPK. PCS at 6, 12, and 24 months after LDSPK were significantly higher than the pretransplantation level. MCS were also significantly higher than the pretransplantation level. LDSPK showed prominent QOL improvement for the recipient. Complications were not observed in any donor. Although PCS decreased at 6 months after the operation, it recovered at 12 and at 24 months after the operation. MCS was maintained at more than 50 from 6 to 24 months after the operation. QOL was well preserved in the LDSPK donors despite the major surgery. In conclusion, LDSPK was confirmed to be a potent tool for treatment of type 1 diabetes mellitus patients with end-stage renal disease (ESRD) by complete normalization of glucose metabolism and renal function. In addition to these medical advantages, both their physical and mental QOL were improved by LDSPK.
Assuntos
Diabetes Mellitus Tipo 1/cirurgia , Nefropatias Diabéticas/cirurgia , Falência Renal Crônica/cirurgia , Transplante de Rim/fisiologia , Transplante de Pâncreas/fisiologia , Qualidade de Vida , Adulto , Pai , Feminino , Humanos , Insulina/uso terapêutico , Transplante de Rim/psicologia , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Mães , Nefrectomia/métodos , Transplante de Pâncreas/psicologia , Pancreatectomia/métodos , Diálise Renal , Inquéritos e QuestionáriosRESUMO
For the safe operation of living donor pancreas transplantation, we investigated the utility of 11C-methionine positron emission tomography (PET) to examine the function of the residual pancreatic head in patients with pancreatic disease undergoing distal pancreatectomy and in living donors of pancreas transplantation. After 6 hours of fasting, we intravenously injected 370 to 740 MBq 11C-methionine. PET was scanned 30 minutes after injection. 11C-methionine PET uptake by the pancreatic head versus body/tail was expressed as a standardized uptake value (SUV). The SUVs of the pancreatic head were compared before versus after surgery. The SUVs of the pancreatic head in patients before and after distal pancreatectomy were 15.3 +/- 6.0 and 18.2 +/- 2.4, respectively. The SUVs of the pancreatic head in donors before and after distal pancreatectomy were 16.1 +/- 1.0 and 14.7 +/- 1.4, respectively. Both patients and donors showed no significant difference in SUVs of the pancreatic head before and after surgery. However, the SUVs of the residual pancreatic head were elevated after distal pancreatectomy in 80% of patients and 50% of donors. These data indicated that the function of the pancreatic head may be maintained or improved after distal pancreatectomy. 11C-methionine PET may become a potent modality to evaluate segmental pancreatic function for a safe living donor operation.
Assuntos
Doadores Vivos , Transplante de Pâncreas/métodos , Pâncreas/anatomia & histologia , Pancreatectomia/métodos , Transporte Biológico , Radioisótopos de Carbono , Humanos , Metionina/metabolismo , Pâncreas/diagnóstico por imagem , Pâncreas/metabolismo , Tomografia por Emissão de Pósitrons/métodos , RadiografiaRESUMO
We performed 6 islet transplantations in 4 type 1 diabetes mellitus patients. From September 2003 to April 2007, 23 islet isolations were performed from pancreata of non-heart-beating donors. The pancreata preserved using a 2-layer method or simple cold storage in University of Wisconsin solution were transferred to our cell processing center. The islet isolation was performed according to the Edmonton protocol with some modifications. The immunosuppressive protocol was achieved using sirolimus, tacrolimus, and anti-CD25 antibody (basiliximab). Islet yield was 400 to 491,040 IEQ and purity was 1% to 70%. Stimulation indices upon static incubation were 1.38 to 11.69. All patients who underwent islet transplantation showed positive serum C-peptide levels immediately after transplantation. Although insulin independence was not achieved, they displayed stabilized blood glucose levels, reduced insulin doses, and disappearance of hypoglycemic unawareness. Although stomatitis and diarrhea due to the side effects of sirolimus were observed in 2 patients, there were no severe complications. In patient 1, serum C-peptide levels decreased gradually from 1 year after transplantation. In conclusion, successful islet transplantation was possible using islets isolated from the pancreata of non-heart-beating donors. Further improvements are needed to achieve prolonged graft survival.
Assuntos
Diabetes Mellitus Tipo 1/cirurgia , Transplante das Ilhotas Pancreáticas/métodos , Glicemia/metabolismo , Cadáver , Separação Celular , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/imunologia , Quimioterapia Combinada , Humanos , Imunossupressores/uso terapêutico , Ilhotas Pancreáticas/citologia , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Doadores de TecidosRESUMO
The stratum corneum (SC) is the interface between the body and the environment, and is continuously exposed to oxidative stress that results in carbonyl modification of proteins. We previously developed a simple and non-invasive method to assess the stratum corneum carbonyl protein (SCCP) levels. In this study, we used this method to examine the seasonal changes in the SCCP levels and the relationship between the SCCP level and the physiological condition of the SC. SC was collected from the face of healthy Japanese volunteers by adhesive tape stripping and its carbonyl groups were determined by reaction with fluorescein-5-thiosemicarbazide. The average fluorescence intensity of the SC was calculated as the SCCP level. The SCCP level in the cheek was higher in winter than summer. The SCCP level was negatively correlated with the water content in the SC measured by the conductance and capacitance, and also negatively correlated with the extensibility of the skin measured by a Cutometer, suggesting that the mechanical properties of the skin can be affected by oxidative modification of the SC. These data suggest the involvement of oxidative modification of SC proteins in the generation of rough skin during winter.
Assuntos
Carbonilação Proteica , Proteínas/metabolismo , Pele/metabolismo , Adolescente , Adulto , Temperatura Baixa , Epiderme/metabolismo , Face , Feminino , Fluoresceínas/química , Humanos , Masculino , Microscopia de Fluorescência , Pessoa de Meia-Idade , Estações do AnoRESUMO
BACKGROUND: Mizoribine (MZ) has been developed as an immunosuppressive agent in Japan, but it has a less-potent immunosuppressive effect up to 3 mg/kg/d. In the previous study, a Japanese multicenter study, we reported that high-dose MZ, at 6 mg/kg/d, with a calcineurin inhibitor was effective and safe in reducing the frequency of cytomegalovirus (CMV)-related events in ABO-incompatible (ABO-i) living-related kidney transplantation (LKT). In the present study, therefore, we investigated the effects of high-dose MZ with a CNI in ABO-i LKT recipients in a Japanese multicenter study. METHODS: A total of 37 patients were treated with high-dose MZ (6 mg/kg), a CNI (cyclosporine [CsA] or tacrolimus [Tac]), basiliximab (Bas), rituximab (Rit), and corticosteroids. CsA was started at a dose of 7 mg/kg to maintain blood levels [200 ng/mL (C0), 6000 ng-h/mL (AUC 0-9)]. Tac was started at a dose of 0.2 mg/kg to maintain blood levels [8-10 ng/mL (C0), 100 ng-h/mL (AUC 0-9)]. Bas (20 mg/body) was administrated on day 0 and day 4 after transplantation. Rit (100-200 mg/body) was administrated on day -14 and day -7 before transplantation. MZ was adjusted to maintain target C0 levels of 1.5 to 2.0 µg/mL. RESULTS: Patient and graft survival rates for 2 years were 100% in the CsA group (n = 22) and 93.3% in the Tac group (n = 15) (not significant, NS). Overall incidence of acute rejection for 2 years was 22.7% in the CsA group and 26.7% in the Tac group. Mean serum creatinine levels at 2 years were 1.29 ± 0.2 mg/dL in the CsA group and 1.21 ± 0.34 mg/dL in the Tac group (NS). The incidence of CMV disease was 0% in both groups, and positive rates of CMV antigenemia were 50.0% and 26.7% in the CsA and Tac groups, respectively (NS). Mean serum uric acid levels were 5.5 ± 1.3 mg/dL and 6.4 ± 1.2 mg/dL at 2 years (NS) in the CsA and Tac groups, respectively. CONCLUSIONS: A high-dose MZ regimen including calcineurin inhibitor (CsA or Tac), Bas, Rit, and steroids was effective and safe in reducing the frequency of CMV-related events in ABO-i LKT.
Assuntos
Incompatibilidade de Grupos Sanguíneos/tratamento farmacológico , Imunossupressores/administração & dosagem , Transplante de Rim/métodos , Ribonucleosídeos/administração & dosagem , Corticosteroides/uso terapêutico , Adulto , Infecções por Citomegalovirus/complicações , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: 1alpha,25-Dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] and its analogues inhibit growth of various types of cancer cells. Although the therapeutic potential of 1,25(OH)(2)D(3) is limited by its tendency to induce hypercalcemia, analogues such as EB1089 are potent inhibitors of cell growth and exhibit reduced calcemic effects. We analyzed the antiproliferative and calcemic effects of EB1089 in tissue culture and animal models of head and neck squamous cell carcinoma (SCC) to investigate its potential as a chemotherapeutic/chemopreventive agent. METHODS: The effects of 1,25(OH)(2)D(3) and EB1089 on cell growth and expression of p21(WAF1/CIP1) and p27(KIP1), which encode cyclin-dependent kinase inhibitors, and a novel target, gadd45alpha, a growth-arrest and DNA-damage gene, were monitored in cultured murine AT-84 SCC cells. The effects of these agents on AT-84 cell growth in vitro and on growth of AT-84 tumors in syngeneic C3H mice were monitored; treatment started at the time of tumor implantation (early tumor model) or after 12 days (late tumor model). Weight and serum calcium levels were also monitored in these animals. All P values were two-sided. RESULTS: Both 1,25(OH)(2)D(3) and EB1089 arrested proliferation of AT-84 cells in G(0)/G(1) phase, inhibited p21(WAF1/CIP1) expression, and induced expression of p27(KIP1) protein. 1,25(OH)(2)D(3) also enhanced the expression of gadd45alpha, apparently by a p53-independent mechanism. There was a statistically significant decrease in tumor growth for 1,25(OH)(2)D(3)-treated mice (P<.001 for early tumor model) and EB1089-treated mice (P<.001 and P =.001 for early and late tumor models, respectively). Unlike 1,25(OH)(2)D(3), EB1089 did not induce cachexia or hypercalcemia. The effects of 1,25(OH)(2)D(3) and EB1089 on expression of p21(WAF1/CIP1) and GADD45alpha were similar in tumors and in vitro. CONCLUSIONS: EB1089 completely inhibited growth of AT-84 SCC cells at nanomolar concentrations, reduced tumor growth, and did not have calcemic effects. Our results support continued investigation of EB1089 as a chemopreventive/chemotherapeutic agent for head and neck SCC.
Assuntos
Antineoplásicos/uso terapêutico , Calcitriol/análogos & derivados , Calcitriol/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Proteínas de Ciclo Celular , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Proteínas Supressoras de Tumor , Animais , Northern Blotting , Western Blotting , Carcinoma de Células Escamosas/prevenção & controle , Ciclo Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Inibidor de Quinase Dependente de Ciclina p21 , Inibidor de Quinase Dependente de Ciclina p27 , Ciclinas/biossíntese , Citoplasma/metabolismo , Dano ao DNA/genética , Genes p53/genética , Neoplasias de Cabeça e Pescoço/prevenção & controle , Imuno-Histoquímica , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Camundongos , Camundongos Endogâmicos C3H , Proteínas Associadas aos Microtúbulos/biossíntese , Transplante de Neoplasias , Testes de Precipitina , Proteínas/metabolismo , RNA/metabolismo , Fatores de Tempo , Células Tumorais Cultivadas , Proteínas GADD45RESUMO
OBJECTIVE: The use of positron-emission tomography (PET) with (18)F-fluorodeoxyglucose (FDG) -labeled islets has been considered to be a potential modality to visualize and quantify early engraftment of islet transplantation. The objective of this study was to evaluate the early islets' survival of the FDG-labeled islets with or without warm ischemic stress in portal transplanted rats using PET and autoradiography. METHODS: Islets were isolated from Lewis rat pancreata with or without 30-minute warm ischemia times (WITs). For islets' labeling, 300 islets were incubated with 3 MBq FDG for 60 minutes. FDG-labeled islets were transplanted into the liver via portal vein. In in vivo study, a PET study was scanned for 90 minutes and the FDG uptake was expressed as percentage of liver injection dose (ID). In ex vivo study, the liver was exposed for 30 minutes with single fluorescence autoradiography. RESULTS: In the PET study, the percentage of liver ID of the islets without WIT was 27.8 and that of the WIT islets was 20.1 at the end of islet transplantation. At 90 minutes after transplantation, the percentage of liver ID was decreased to 14.7 in the islets without WIT and 10.1 in the WIT islets. In the autoradiogram, the number of hot spots was more obviously visualized in the liver transplanted without WIT islets than in the liver transplanted with WIT islets. CONCLUSION: Almost 50% of the islets were immediately lost in both the islets without WIT and those with WIT transplantation in the early period. However, islet survival was 1.4 times higher in the islets without WIT than that in those with WIT in the early engraftment phase.
Assuntos
Autorradiografia/métodos , Transplante das Ilhotas Pancreáticas/métodos , Ilhotas Pancreáticas/diagnóstico por imagem , Veia Porta/transplante , Tomografia por Emissão de Pósitrons/métodos , Animais , Sobrevivência Celular , Fluordesoxiglucose F18 , Ilhotas Pancreáticas/fisiopatologia , Fígado , Masculino , Compostos Radiofarmacêuticos , Ratos , Ratos Endogâmicos Lew , Coloração e Rotulagem , Transplantes , Isquemia Quente/efeitos adversosRESUMO
Analogs of 1alpha,25-dihydroxyvitamin D(3) (1alpha, 25(OH)2D3) inhibit growth in vitro and in vivo of cells derived from a variety of tumors. Here, we examined the effects of 1alpha,25(OH)2D3 and its analog EB1089 on proliferation and target gene regulation of human head and neck squamous cell carcinoma (SCC) lines SCC4, SCC9, SCC15, and SCC25. A range of sensitivities to 1alpha,25(OH)2D3 and EB1089 was observed, from complete G0/G1 arrest of SCC25 cells to only 50% inhibition of SCC9 cell growth. All lines expressed similar levels of vitamin D3 receptor (VDR) mRNA and protein, and no significant variation was observed in 1alpha,25(OH)2D3-dependent induction of the endogenous 24-hydroxylase gene, or of a transiently transfected 1alpha,25(OH)2D3-sensitive reporter gene. The antiproliferative effects of 1alpha,25(OH)2D3 and EB1089 in SCC25 cells were analyzed by screening more than 4,500 genes on two cDNA microarrays, yielding 38 up-regulated targets, including adhesion molecules, growth factors, kinases, and transcription factors. Genes encoding factors implicated in cell cycle regulation were induced, including the growth arrest and DNA damage gene, gadd45alpha, and the serum- and glucocorticoid-inducible kinase gene, sgk. Induction of GADD45alpha protein in EB1089-treated cells was confirmed by Western blotting. Moreover, while expression of proliferating cell nuclear antigen (PCNA) was reduced in EB1089-treated cells, coimmunoprecipitation studies revealed increased association between GADD45alpha and PCNA in treated cells, consistent with the capacity of GADD45alpha to stimulate DNA repair. While 1alpha,25(OH)2D3 and EB1089 modestly induced transcripts encoding the cyclin-dependent kinase inhibitor p21(waf1/cip1), no changes in protein levels were observed, indicating that p21(waf1/cip1) induction does not contribute to the antiproliferative effects of 1alpha,25(OH)2D3 and EB1089 in SCC cells. Finally, in partially resistant SCC9 cells, there was extensive loss of target gene regulation (10 of 10 genes tested), indicating that resistance arises from widespread loss of 1alpha,25(OH)2D3-dependent gene regulation in the presence of normal levels of functional VDRs.
Assuntos
Calcitriol/farmacologia , Carcinoma de Células Escamosas/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias de Cabeça e Pescoço/patologia , Proteínas Supressoras de Tumor , Northern Blotting , Calcitriol/análogos & derivados , Carcinoma de Células Escamosas/genética , Proteínas de Ciclo Celular/genética , Divisão Celular/efeitos dos fármacos , Inibidor de Quinase Dependente de Ciclina p21 , Inibidor de Quinase Dependente de Ciclina p27 , Quinases Ciclina-Dependentes/antagonistas & inibidores , Ciclinas/genética , Resistência a Medicamentos , Neoplasias de Cabeça e Pescoço/genética , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Análise de Sequência com Séries de Oligonucleotídeos , Antígeno Nuclear de Célula em Proliferação/metabolismo , Proteínas/genética , Proteínas/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transfecção , Células Tumorais Cultivadas , Proteínas GADD45RESUMO
Threo-Ds-3-isopropylmalate dehydrogenase coded by the leuB gene from an extreme thermophile, Thermus thermophilus strain HB8, was expressed in Escherichia coli carrying a recombinant plasmid. The thermostable enzyme thus produced was extracted from the E. coli cells, purified, and crystallized. The enzyme was shown to be a dimer of identical subunits of molecular weight (4.0 +/- 0.5) x 10(4). The Km for threo-Ds-3-isopropylmalate was estimated to be 8.0 x 10(-5) M and that for NAD 6.3 x 10(-4) M. The optimum pH at 75 degrees C in the presence of 1.2 M KCl was around 7.2. The presence of Mg2+ or Mn2+ was essential for the enzyme action. The enzyme was activated about 30-fold by the addition of 1 M KCl or RbCl. The high salt concentration decelerated the thermal unfolding of the enzyme, and accelerated the aggregation of the unfolded protein. Based on these effects, the molecular mechanism of the unusual stability of the enzyme is discussed.
Assuntos
Oxirredutases do Álcool/genética , Escherichia coli/genética , Genes Bacterianos , Thermus/genética , 3-Isopropilmalato Desidrogenase , Oxirredutases do Álcool/química , Cátions/farmacologia , Clonagem Molecular , Estabilidade Enzimática , Temperatura Alta , Desnaturação Proteica , Especificidade por Substrato , Termodinâmica , Thermus/efeitos dos fármacos , Thermus/enzimologia , Ureia/farmacologiaRESUMO
A chimeric gene was constructed by fusing the Bacillus subtilis and Thermus thermophilus genes coding for 3-isopropylmalate dehydrogenase, and expressed in Escherichia coli. The chimeric enzyme was crystallized in a size suitable for X-ray structure analysis. The crystal has a space group of P3(1)21 or P3(2)21, a = b = 77.1 A and c = 158.3 A, which is isomorphous with that of the native enzyme from T. thermophilus.
Assuntos
Oxirredutases do Álcool/genética , 3-Isopropilmalato Desidrogenase , Oxirredutases do Álcool/química , Bacillus subtilis/enzimologia , Bacillus subtilis/genética , Clonagem Molecular , Cristalização , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Thermus/enzimologia , Thermus/genética , Difração de Raios XRESUMO
We have performed retroperitoneoscopic nephrectomy for living kidney donor surgery since 2000. Recently, we introduced single-site retroperitoneoscopic donor nephrectomy (RDN) as a less invasive donor surgery. The procedure was performed in 7 donors (5 women and 2 men) by a single surgeon. The mean age and body mass index of the donors were 62.6 years (range, 53-74 years) and 24.3 kg/m(2) (range, 22.3-29.0 kg/m(2)), respectively. Left-sided nephrectomy was performed in all the donors. The donors were positioned in the right lateral position, and a 7-cm-long incision was made in the left flank. The incision was extended to the retroperitoneal space using the muscle-splitting technique. The retroperitoneal space was then expanded using an inflation balloon. A GelPOINT Advanced Access Platform (Applied Medical, Rancho Santa Margarita, Calif, United States) was placed in the incision. The subsequent technique and equipment were the same as those used in conventional 3-port RDN. The renal artery and vein were dissected using a vascular stapler, and the kidney graft was directly extracted through the incision. The mean operative time was 197 ± 28 minutes, warm ischemic time was 4.1 ± 1.2 minutes, and blood loss was 75 ± 113 mL. No statistical differences were found between the present method and conventional 3-port RDN. Intraoperative and postoperative complications were not observed in any of the donors. Graft function after transplantation was good, and delayed graft function was not observed in any of the recipients. This technique can be easily introduced in the clinical setting by surgeons experienced in RDN.
Assuntos
Transplante de Rim , Doadores Vivos , Nefrectomia/métodos , Segurança do Paciente , Espaço Retroperitoneal/cirurgia , Idoso , Feminino , Taxa de Filtração Glomerular , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
We recently reported that (11)C-methionine positron-emission tomography (PET) is clinically useful for the evaluation of the pancreatic function of the living donor. The objective of this study was to evaluate the postoperative insulin independence in 10 living donor (LD) and 10 brain-dead donor (BD) pancreas transplantations for 20 patients with type I diabetes mellitus by using (11)C-methionine PET. After 6 months, PET/computed tomography was performed 30 minutes after (11)C-methionine (370-740 MBq) injection. The uptake in the pancreas was expressed as the standardized uptake value (SUV). Patient survival rates were 100% at 5 years for LD transplantations and at 2 years for BD transplantations. Insulin independence was 60% for LD transplantations at 5 years and 75% for BD transplantations at 2 years. There were no major surgical complications such as vascular thrombosis, intra-abdominal abscess, and graft pancreatitis. The SUVs for LD and BD pancreas transplantations with insulin independence were 7.2 ± 1.8 and 10.4 ± 2.3, respectively. The SUVs for LD pancreas transplantations with insulin dependence and BD pancreas transplantations with graft failure were 3.6 ± 1.1 and 2.9 ± 1.0, respectively. At 5 years after transplantation, for the LD transplants, the insulin-independent rate was 100% for the graft recipients with an SUV higher than 5, and the median insulin independence duration of the graft recipients with an SUV less than 5 was 7 months (P < .01). The (11)C-methionine PET may be a potent modality to predict long-term insulin independence and the avoidance of pancreas graft failure.
Assuntos
Diabetes Mellitus Tipo 1/cirurgia , Transplante de Pâncreas , Pâncreas/diagnóstico por imagem , Adulto , Morte Encefálica , Peptídeo C/sangue , Radioisótopos de Carbono , Feminino , Hemoglobinas Glicadas/análise , Humanos , Doadores Vivos , Masculino , Metionina , Pâncreas/fisiologia , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Tomografia Computadorizada por Raios XRESUMO
In the present study, we aimed to compare the pancreas volumetric changes before and after living donor surgery for pancreas transplantation, using three-dimensional (3D) computed tomography (CT) and glucose metabolism. Pancreatic volume (PV) measurement using 3D CT was performed in 13 consecutive donors who underwent distal pancreatectomy for simultaneous living donor pancreas and kidney transplantation. PV was measured using a workstation before and 3 months after living donor operation. As the parameters of glucose metabolism, hemoglobin A1c (HbA1c) level, fasting plasma glucose (FPG) level, body mass index (BMI), homeostasis model assessment of insulin resistance (HOMA-IR), and insulinogenic index (IGI) were examined simultaneously with the PV measurement. The preoperative and postoperative PVs of pancreas was 30 ± 5 mL and 42 ± 9 mL, respectively. The postoperative PV was significantly higher than the preoperative PV (P < .01) and increased by approximately 40% at 3 months after surgery. The postoperative FPG and HbA1c levels were significantly higher than the preoperative values (P < .01). BMI decreased significantly after surgery (P < .01). No differences in HOMA-IR and IGI were noted between before and after surgery. Diabetes mellitus was not observed any of the 13 living donors during this period. Distal pancreatectomy for living donors caused an increase in the PV and maintained insulin resistance, but it was not sufficient to maintain glucose metabolism at the preoperative state.
Assuntos
Glicemia/metabolismo , Doadores Vivos , Transplante de Pâncreas , Pâncreas/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do ÓrgãoRESUMO
BACKGROUND: Transforming growth factor (TGF)-ß1 may contribute to chronic allograft nephropathy and graft loss; however, the exact molecular mechanism remains unclear. Therefore, we assess the relationship between TGF-ß1 gene polymorphisms, expression, and development of allograft nephropathy. METHODS: We studied 135 renal transplant recipients at our hospital. TGF-ß1 gene polymorphisms (codons 10 and 25) were determined from peripheral blood leukocyte DNA. Plasma TGF-ß1 mRNA was measured by real-time polymerase chain reaction and TGF-ß1 protein levels were assessed by enzyme-linked immunosorbent assay. The relationship between TGF-ß1 genotyping, expression, and rejection and results of renal biopsy were evaluated. RESULTS: The genotype frequency of transplant recipients was 49.6%, 30.4%, and 20.0% for C/T, C/C and T/T at codon 10, 100% for G/G at codon 25, respectively. According to the criteria of Banff '97 classification, 24 cases were classified as acute rejection and whose genotypes were 16, 3, and 5 cases for C/T, C/C and T/T at codon 10. Plasma mRNA expression was elevated in 14 cases and decreased in 8 cases after acute rejection. We measured 267 specimens of TGF-ß1 protein and there was no relation between amount of TGF-ß1 protein and mRNA. CONCLUSION: Our results suggest that the relationship between plasma TGF-ß1 expression and the development of allograft nephropathy remains uncertain. Frequency of allograft rejection differ with TGF-ß1 codon 10 genotypes and the high-risk genotype was different from the reports of other countries.
Assuntos
Transplante de Rim , RNA Mensageiro/genética , Fator de Crescimento Transformador beta1/genética , Feminino , Genótipo , Humanos , Japão , Masculino , Fator de Crescimento Transformador beta1/metabolismoRESUMO
PURPOSE: BK polyomavirus-associated nephropathy (BKVAN) is an important cause of renal allograft loss. Immunosuppression therapy in renal transplant recipients can lead to the reactivation of latent BK polyomavirus (BKV) infection, leading to BK viruria and viremia. This single-center study aimed to clarify the association between quantitative measurement of BKV DNA and the progression of BKV infection, and secondly to identify the risk factors associated with the evolution of viruria to viremia. METHODS: We retrospectively analyzed 266 patients who underwent renal transplantation in our center from October 2006 to February 2013. We examined the viral loads of BKV in urine and plasma by quantitative real-time polymerase chain reaction assay after screening all of the recipients by urinary sediment examination. BKVAN was diagnosed by histological examination with immunohistochemistry of the large T antigen in biopsy specimens. RESULTS: Overall, 22 recipients showed BK viruria alone, whereas 22 progressed to BK viremia, of which 6 patients were diagnosed with BKVAN. Among BKVAN patients, 2 cases progressed to graft loss at 59 months and 31 months after diagnosis, respectively. In BKVAN group, the plasma viral loads were significantly higher than those in viremia without nephropathy (P < .001). Multivariate analysis revealed that the evolution of viruria to viremia was associated with recipient age over 55 years (odds ratio, 32.08; 95% confidence interval, 2.1-489.5) and tacrolimus exposure (odds ratio, 11.98; 95% confidence interval, 1.34-107.04). CONCLUSIONS: The progression from viremia to BKVAN was strongly associated with increasing plasma viral loads for BKV DNA. The cutoff value of 1 × 10(4) copies/mL for plasma viral loads could differentiate between BKVAN and viremia alone. Further, recipient age over 55 years and tacrolimus exposure were independently associated with the evolution of viruria to viremia.
Assuntos
Vírus BK/genética , DNA Viral/genética , Transplante de Rim , Infecções por Polyomavirus/complicações , Vírus BK/isolamento & purificação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Carga ViralRESUMO
Common iliac artery stenosis after renal transplantation is a rare complication; it can occur in the course of hypertension and renal dysfunction. We report a case of suspected renal allograft rejection with iliac artery stenosis proximal to a transplanted kidney. A 52-year-old man with a history of cadaveric kidney transplantation 26 years previously underwent a second cadaveric kidney transplantation in the left iliac fossa because of graft failure 3 years before. In June 2012, the patient had progressive renal dysfunction. In July, a percutaneous needle biopsy was taken, and it showed no rejection; however, his renal function continued to get worse through September. A percutaneous allograft renal biopsy was performed under ultrasound guidance and showed hyperplasia of the juxtaglomerular apparatus and renin granules. Magnetic resonance angiography was used to evaluate the arteries in the pelvis and showed left common iliac artery stenosis, and a stent was placed. After percutaneous intervention, the patient's ankle brachial pressure index was within the normal range and the allograft function had improved.
Assuntos
Biópsia , Constrição Patológica/diagnóstico , Transplante de Rim , Rim/patologia , Artéria Renal/patologia , Adulto , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND AND PURPOSE: Findings on MR imaging of carotid plaques correlate with histologic findings and may be useful in identifying vulnerable plaques. The objective of this study was to show how MR imaging findings and clinical factors could be used to construct a preliminary model and a nomogram for predicting the risk of new ischemic lesions on DWI following CEA or CAS. MATERIALS AND METHODS: One hundred four patients with carotid stenosis undergoing treatment (63 CEA, 41 CAS) were prospectively enrolled (mean age, 71.7 ± 7.0 years; 11 women). T1-SIR and T2-SIR of carotid plaque were measured on MR imaging. Associations among carotid MR imaging findings, treatment procedures, degree of stenosis, cardiovascular risk factors, and occurrence of new ischemic lesions on DWI 1 day after treatment were studied by multivariate logistic regression. RESULTS: One stroke occurred after CAS (2.4%), and none after CEA. New DWI lesions after treatment were observed in 25 patients (24%). Our preliminary prediction model demonstrated that T1-SIR (OR [per 0.5 increase], 3.99; 95% CI, 2.18-7.31; P < .0001) and CAS (OR, 2.06; 95% CI, 1.01-4.24; P = .048 compared with CEA) were positively associated with new DWI lesions on posttreatment DWI scans. T2-SIR (OR [per 0.5 increase], 0.74; 95% CI, 0.55-0.98; P = .037) was negatively associated. The C-index of this model was 0.79 (95% CI, 0.69-0.89), which indicated some utility in predicting the response. CONCLUSIONS: Our preliminary prediction model and nomogram may provide an individualized risk estimate of new ischemic lesions after CEA or CAS and useful information for decision-making regarding treatment strategy.
Assuntos
Isquemia Encefálica/etiologia , Artéria Carótida Interna/patologia , Estenose das Carótidas/cirurgia , Imagem de Difusão por Ressonância Magnética , Endarterectomia das Carótidas , Placa Aterosclerótica/diagnóstico , Stents , Idoso , Artéria Carótida Interna/cirurgia , Estenose das Carótidas/patologia , Endarterectomia das Carótidas/efeitos adversos , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Modelos Estatísticos , Nomogramas , Medição de Risco , Stents/efeitos adversosRESUMO
OBJECTIVE: In Japan, >80% of kidney transplantations (KTs) are performed from living donors because of a severe shortage of deceased donors. Moreover, >90% of deceased donors are non-heart-beating donors. In this study, we compared the quality of life (QOL) of the recipients between living- and deceased-donor KT performed in our hospital. METHODS: QOLs of 91 recipients (11 deceased donors and 80 living donors) were analyzed using the Short Form 36 before and 1, 2, and 3 years after KT. Changes in QOLs were compared between deceased-donor KT (group DD) and living-donor KT (group LD). RESULTS: In group DD, physical (PCS) and mental (MCS) component summary scores before transplantation were 43.7 and 48.7, respectively. PCS decreased to 35.3 at 1 year and 34.2 at 2 years, but increased to 52.6 at 3 years. MCS as 43.2 at 1 year, 52.2 at 2 years, and 44.5 at 3 years. In group LD, PCS and MCS before transplantation were 36.9 and 42.6, respectively. PCS increased to 43.3 at 1 year, 47.6 at 2 years, and 51.0 at 3 years, and MCS increased to 47.8 at 1 year, 50.1 at 2 years, and 49.6 at 3 years. CONCLUSIONS: The recipients of living-donor KT showed an improvement of QOL immediately after transplantation. However, in the recipients of deceased-donor KT, physical QOL (PCS) decreased for 2 years after transplantation. The reasons seem to be long waiting period and the use of non-heart-beating donors in deceased-donor KT in Japan.