RESUMEN
We evaluated the dissociation of isolated gas-phase nucleobase molecules induced by mega electron volt (MeV)-energy ions to gain fundamental insights into the reactions of nucleobases upon fast ion irradiation. We studied five nucleobase molecules-adenine, guanine, cytosine, thymine, and uracil-as gas-phase targets. We compared the fragmentation patterns obtained from carbon ion impacts with those obtained from proton impacts to clarify the effect of heavy ion irradiation. We also compared the results with electron impact and photoionization results. In addition, we identified several delayed fragmentation pathways by analyzing the correlation between fragment pairs generated from singly and doubly charged intermediate ions. To determine the lifetimes of delayed fragmentation from singly charged intermediate ions, we evaluated the detection efficiencies of the microchannel plate detector for the neutral fragment HCN as a function of kinetic energy using a new methodology. As the first demonstration of this method, we estimated the lifetimes of C5H5N5+ generated by 1.2-MeV C+ and 0.5-MeV H+ collisions to be 0.87 ± 0.43 and 0.67 ± 0.09 µs, respectively. These lifetimes were approximately one order of magnitude longer than those of the doubly charged intermediate ion C5H5N52+.
RESUMEN
BACKGROUND: Isolated superior mesenteric artery (SMA) dissection (SMAD) is considered a relatively rare disease. Especially, isolated SMAD following liver transplant has been rarely reported. REPORT OF CASES: Among 96 consecutive adult recipients who underwent liver transplant at our institution, 3 recipients (3.1%) demonstrated isolated noncommunicating SMAD, type IV according to Sakamoto's classification. Patient characteristics are the following: mean age, 53 years (range, 49-60 years); male to female ratio, 2:1, right lobe graft to left lobe graft ratio, 2:1; operating time, 760 minutes (range, 614-880 minutes); and blood loss, 6570 mL (range, 2435-13,329 mL). New onset of abdominal pain was noted in 33.3% (1/3). The diagnosis was made by the first follow-up computed tomography scan after liver transplant. The mean distance between the proximal end of SMAD and the root of SMA was 21.3 mm (range, 9-40 mm). There were no signs of ischemic changes in the small intestine in any of the 3 patients. Thus, conservative managements such as anticoagulation therapy were performed without other aggressive interventions. One patient died because of subarachnoid hemorrhage. In the other 2 patients, SMAD disappeared at 6 months following the diagnosis. DISCUSSION: The morbidity of isolated SMAD is around less than 0.1% at the autopsy. Compared with this result, we found significantly higher morbidity rate in liver transplant recipients. It is true that mechanical stress from retraction of the stomach to the caudal end including the root of SMA may play an important role in the onset of SMA dissection. CONCLUSION: Isolated SMA dissection following living donor liver transplant is a rare but potentially life-threatening condition. It is required to ascertain whether emergency revascularization should be considered.
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Disección Aórtica/etiología , Trasplante de Hígado/efectos adversos , Arteria Mesentérica Superior/patología , Anciano , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Recently, myeloid-derived suppressor cells (MDSCs) have attracted considerable attention because of their cancer-promoting and immunosuppressive effects. The glucocorticoid dexamethasone (Dex) is an important immunosuppressive agent used to treat autoimmune diseases and organ transplant rejection. However, the mechanism by which it modulates the immune system is not completely understood. MATERIAL AND METHODS: In this study, we investigated the mechanisms by which Dex modulated the immune response in mice given an allogeneic cardiac transplant. RESULTS: Dex injection significantly prolonged heart graft survival compared with phosphate-buffered saline-injected controls. Dex treatment increased the number of splenic MDSCs. Moreover, Gr-1high/CD11b+ MDSCs and CD3+/CD4+/Foxp3+ regulatory T cells (Tregs) were significantly increased in the Dex group compared with controls. Administration of anti-Gr-1 antibody (Ab) to the Dex group significantly shortened mouse heart graft survival. In addition, anti-Gr-1 Ab treatment significantly reduced Tregs in the Dex + anti-Gr-1 co-treatment group compared with the Dex group. These observations suggest that Dex treatment increased both MDSCs and Tregs, and that MDSCs regulated the incidence of Tregs in this immunosuppressive pathway. CONCLUSION: An important role of Dex in the prevention of the rejection of cardiac grafts in mice is to expand MDSCs and Tregs.
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Aloinjertos/efectos de los fármacos , Dexametasona/farmacología , Supervivencia de Injerto/efectos de los fármacos , Trasplante de Corazón , Corazón/efectos de los fármacos , Inmunosupresores/farmacología , Células Supresoras de Origen Mieloide/efectos de los fármacos , Aloinjertos/inmunología , Animales , Supervivencia de Injerto/inmunología , Masculino , Ratones , Ratones Endogámicos C3H , Ratones Endogámicos C57BL , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos T Reguladores/inmunologíaRESUMEN
Preservation of fertility has been recommended for cancer-bearing patients of reproductive age before undergoing cancer treatment. However, there are many considerations and it is difficult to preserve fertility for all patients undergoing therapy for malignancies. Female cancer survivors had lower pregnancy and live birth rates compared with others that underwent assisted reproductive technologies (ARTs). We should continue to consider the issue of infertility in patients who underwent therapies for malignancies. This is the first report of a successful live birth in a patient with a cranial tumor who underwent radiotherapy and chemotherapy after implantation of an autologous embryo. The patient was a 27-year-old Japanese woman. She was diagnosed with suprasellar germinoma at 13 years of age, and she developed panhypopituitarism after radiotherapy and chemotherapy. At 27 years of age, she began infertility treatment with in-vitro fertilization (IVF). The level of anti-Mallerian hormone (AMH) was 4.29 ng/ml. After ovarian stimulation by high purified human menopausal gonadotropin (HP-hMG), she obtained two blastocysts and became pregnant by implantation of a cryopre- served blastocyst. At 37 gestational weeks, she delivered a healthy female baby by cesarean section.
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Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/radioterapia , Germinoma/tratamiento farmacológico , Germinoma/radioterapia , Adulto , Blastocisto , Criopreservación , Implantación del Embrión , Femenino , Fertilización In Vitro , Humanos , Nacimiento Vivo , Inducción de la Ovulación , Embarazo , Técnicas Reproductivas AsistidasRESUMEN
Neutropenia may develop as an adverse event in patients with multiple myeloma receiving lenalidomide (LEN) plus dexamethasone (DEX) therapy. In the present study, we examined the risk factors associated with grade 3/4 neutropenia during the first cycle of LEN plus DEX therapy. We observed that hemoglobin level (≤ 8.5 g/dl) was a significant risk factor for grade 3/4 neutropenia during the first cycle of therapy (odds ratio: 19.40; 95% confidence interval: 2.68-141.00; p < 0.01). thus, our findings suggest that determining the hemoglobin level could be useful in the risk management for neutropenia in patients receiving LEN plus DEX therapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Mieloma Múltiple/complicaciones , Neutropenia/inducido químicamente , Neutropenia/epidemiología , Anciano , Anciano de 80 o más Años , Antineoplásicos/administración & dosificación , Antineoplásicos Hormonales/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Dexametasona/administración & dosificación , Femenino , Hemoglobinas/metabolismo , Humanos , Lenalidomida , Masculino , Persona de Mediana Edad , Mieloma Múltiple/tratamiento farmacológico , Factores de Riesgo , Talidomida/administración & dosificación , Talidomida/análogos & derivadosRESUMEN
BACKGROUND: Among living donor liver transplant (LDLT) recipients, the number of elderly individuals has been increasing because of longer survival due to the improvement of treatment for hepatic diseases such as hepatitis C (HCV). Here we report the outcomes of living donor recipients over the age of 60 years. MATERIALS AND METHODS: In 76 adult LDLT patients at our institution before September 2015, there were 21 recipients over 60 years old. We divided all of the recipients into 2 groups ("elderly" recipient group >60 years of age [n = 21], and a "nonelderly" recipient group <60 years [n = 55]), and we investigated outcomes in each group. RESULTS: The graft survival rates in the elderly group were 89.9% at 1 year, 89.9% at 3 years, 83.0% at 5 years, and 83.0% at 10 years. The graft survival rates in the nonelderly group was 91.1% at 1 year, 85.2% at 3 years, 82.8% at 5 years, and 82.9% at 10 year. There was no significant difference between the 2 age groups. In the elderly group, 3 patients died (2 patients had HCV recurrence and 1 patient had fungal infection in the brain, leading to a fatal subarachnoid hemorrhage). In the nonelderly group, 4 of 10 patients died of graft failure due to the graft size being too small. CONCLUSION: Elderly patients, at the end stage of liver failure, are likely very frail and may have latent infections. Careful examination for latent infections before LDLT should be carefully performed in regard to indications for LDLT, which might reach satisfactory outcomes as in nonelderly LDLT recipients. Even if elderly patients are approved for transplantation, very careful management is needed.
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Enfermedad Hepática en Estado Terminal/cirugía , Trasplante de Hígado , Adulto , Factores de Edad , Anciano , Estudios de Cohortes , Enfermedad Hepática en Estado Terminal/mortalidad , Femenino , Supervivencia de Injerto , Humanos , Japón , Donadores Vivos , Masculino , Persona de Mediana Edad , Selección de Paciente , Recurrencia , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
INTRODUCTION: Myeloid-derived suppressor cells (MDSCs) play an important role in regulating allograft rejection in organ transplantation. On the other hand, CD3(+)/CD4(+)/FOXP3(+) regulatory T cells (Tregs) also are of vital importance in immunological tolerance. We previously revealed that adoptive transfer of MDSCs recruited Tregs in the spleen. However, it is still uncertain whether MDSCs are capable of recruiting Tregs to an allograft in vivo. OBJECTIVES: We conducted adoptive transfer experiments of MDSCs to clarify the effects of MDSCs on Tregs in vivo. METHODS: Gr-1(+)/CD11b(+) MDSCs were isolated from rapamycin-treated cardiac transplant (CTx) recipients (3 mg/kg, intraperitoneally on postoperative days [POD] 0, 2, 4, and 6) on POD 7 by magnetic-activated cell sorting (purity >95%). In murine heterotopic cardiac transplantation, 2 × 10(6) MDSCs were transferred into the graft aorta 5 minutes before reperfusion. RESULTS: Flow cytometric analyses of a cardiac allograft on POD 7 showed that MDSCs derived from rapamycin-treated CTx mice (MDSCs-Rap) transfer led to significant recruitment of Tregs compared with a PBS-injected allograft. The level of programmed death ligand-1 (PD-L1) on MDSCs-Rap was higher than those from non-treated recipients. Furthermore, pathological findings also confirmed accumulation of Foxp3(+) Tregs in an allograft. CONCLUSION: Induced PD-L1 on MDSCs might result in recruitment of Tregs. These results suggested that functional MDSCs possessed an ability to induce Tregs in a cardiac allograft and developed a tendency to immunological tolerance.
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Factores de Transcripción Forkhead/metabolismo , Trasplante de Corazón , Células Supresoras de Origen Mieloide/fisiología , Linfocitos T Reguladores/inmunología , Traslado Adoptivo/métodos , Aloinjertos/inmunología , Animales , Antígeno CD11b/metabolismo , Linfocitos T CD4-Positivos/inmunología , Tolerancia Inmunológica/fisiología , Inmunosupresores/farmacología , Masculino , Ratones Endogámicos C57BL , Sirolimus/farmacología , Trasplante HomólogoRESUMEN
BACKGROUND: Everolimus (EVR) has been used widely for the purpose of reducing the dosage of calcineurin inhibitor (CNI), leading to decreasing CNI nephrotoxicity. In Japan, high-dose mizoribine (MZR) (6 mg/kg/day) has been increasingly used because of incidences of virus infection and gastrointestinal disorder in kidney transplant recipients. However, the efficacy and safety of EVR and MZR combination therapy is still uncertain. METHODS: A total of 29 living kidney transplant recipients from October 2012 to June 2014 were analyzed. Tacrolimus (TAC), MZR, basiliximab, and prednisolone were administered to all recipients. EVR was added to the regimen for 10 recipients from postoperative day 10 to 14; TAC trough levels were minimized simultaneously (EVR group). The remaining 19 recipients were defined as the control group. We evaluated the outcomes between the 2 groups. RESULTS: The mean TAC trough level was 5.17 ng/mL at 1 month after transplantation in the EVR group, and 7.89 ng/mL in the control group (P = .007), respectively. The mean TAC trough level was 4.0 ng/mL at 18 months after transplantation in the EVR group, and 6.97 ng/mL in the control group (P = .003) respectively. There were no differences in the rate of acute rejection and serum creatinine level. There was no significant difference in the incidence of histological nephrotoxicity between the 2 groups in the 1-year biopsy results. CONCLUSIONS: We succeeded in reducing TAC trough level immediately after transplantation by adding EVR. Our study results suggest that this combination therapy is effective for kidney transplantation recipients.
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Everolimus/uso terapéutico , Inmunosupresores/uso terapéutico , Trasplante de Riñón , Ribonucleósidos/uso terapéutico , Tacrolimus/uso terapéutico , Receptores de Trasplantes , Adulto , Anciano , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Femenino , Humanos , Inmunosupresores/sangre , Donadores Vivos , Masculino , Persona de Mediana Edad , Tacrolimus/sangre , Adulto JovenRESUMEN
This study was retrospectively carried out to compare the efficacy of echinocandins such as micafungin (MCFG) and caspofungin (CPFG) in the treatment of antibiotic-unresponsive febrile patients with hematologic malignancies. A total of 163 patients received either MCFG or CPFG. We evaluated the efficacy of echinocandin against fever decline in all patients. Fever decline, defined as a body temperature of less than 37.5 °C sustained for more than 48 h without scheduled antipyretic medication. Efficacy assessments showed that the incidence of fever decline was not significantly different between the MCFG and CPFG groups (P=0.599). The median number of days from the start of echinocandin administration to fever decline was 5 in both the MCFG and CPFG groups. Multivariate analysis showed that the use of anti-MRSA drugs (HR, 0.64; 95%CI, 0.45-0.90; P=0.011) and a change from echinocandins to voriconazole or liposomal-amphotericin B (HR, 0.50; 95%CI, 0.30-0.74; P<0.001) are significant risk factors for sustained fever. A significant difference (P=0.002) in incidence of fever decline was however associated with differences in the timing of anti-MRSA drug administration. The median number of days from the start of echinocandin administration to fever decline was 5 when administration of the anti-MRSA drug occurred "simultaneously or prior to echinocandin start" and 11 in the "next day or later of echinocandin start" group. In other words, starting anti-MRSA drug treatment after echinocandin treatment is a risk factor. In conclusion, MCFG and CPFG have similar efficacy as empirical antifungal agents in the treatment of antibioticunresponsive febrile patients with hematopoietic malignancies.
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Antifúngicos/uso terapéutico , Equinocandinas/uso terapéutico , Fiebre/tratamiento farmacológico , Fiebre/etiología , Neoplasias Hematológicas/complicaciones , Lipopéptidos/uso terapéutico , Micosis/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Caspofungina , Farmacorresistencia Fúngica , Femenino , Humanos , Masculino , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Micafungina , Persona de Mediana Edad , Micosis/complicaciones , Estudios Retrospectivos , Factores de Riesgo , Infecciones Estafilocócicas/tratamiento farmacológico , Adulto JovenRESUMEN
OBJECTIVE: It was the purpose of this study to determine the effects of non-esterified fatty acids (NEFA) concentrations at different time periods of the transition period as well as lactation number on metabolism, health, reproduction and milk production in dairy cows. MATERIAL AND METHODS: This trial was conducted in a single dairy herd located in Northern Germany. Of the herd, which comprised 330 lactating Holstein cows housed in a free stall barn and fed a total mixed ration (TMR), 83 primiparous and multiparous cows were randomly selected. Animals were checked for body condition score (BCS), locomotion score, calving data, quality of colostrum, reproductive measures, daily rectal temperature of the first 10 days post-partum (p. p.), health data and culling rates up to 200 days in milk (DIM) as well as milk production until 305 DIM. Three different time periods were considered: 3 and 1 week ante partum (a. p.); partus and 1 week p. p.; 3 weeks p. p. RESULTS: Animals with NEFA concentrations ≥ 0.4 mmol/l ante partum had a higher risk of no ovarian activity in week 5 p. p. and of subclinical ketosis post partum than cows with lower NEFA concentrations (p < 0.05). Cows with NEFA concentrations ≥ 1.1 mmol/l in week 1 p. p., in comparison to those with lower NEFA concentrations, showed a higher prevalence of clinical ketosis (24.1% vs. 5.9%), subclinical ketosis (62.1% vs. 34.0%) and culling rate within 200 DIM (34.5% vs. 14.0%) (pââââ<âââ0.05). Cows with NEFA concentrations ≥ 0.3 mmol/l at week 3 p. p. had higher 100- and 305-day milk yields than cows with lower NEFA concentrations (p < 0.05). First lactating heifers were at higher risk to loose body condition ante partum, of dystocia, fever within the first 10 DIM, metritis, clinical and subclinical ketosis as well as to develop a disease within the first 30 DIM (p < 0.05). Multipara were more likely to loose body condition after calving, to a prolonged calving to first service interval and to higher milk yields (p < 0.05). CONCLUSION: In conclusion increased NEFA concentrations during the transition period as well as parity can have an influence on health, production and reproduction of dairy cows.
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Bovinos/fisiología , Ácidos Grasos no Esterificados/sangre , Lactancia/fisiología , Reproducción/fisiología , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Bovinos/sangre , Enfermedades de los Bovinos/fisiopatología , Industria Lechera/métodos , Femenino , Cetosis/fisiopatología , Cetosis/veterinaria , Leche/fisiologíaRESUMEN
Mammalian target of rapamycin (mTOR) inhibitors are the main immunosuppressive drugs for organ transplant recipients. Nevertheless, the mechanisms by which mTOR inhibitors induce immunosuppression is not fully understood. Myeloid-derived suppressor cells (MDSCs) maintain host immunity; however, the relationship between mTOR inhibitors and MDSCs is unclear. Here, the results from a murine cardiac transplantation model revealed that rapamycin treatment (3 mg/kg, intraperitoneally on postoperative days 0, 2, 4, and 6) led to the recruitment of MDSCs and increased their expression of inducible nitric oxide synthase (iNOS). Immunohistochemical analysis revealed that rapamycin induced the migration of iNOS-expressing MDSCs into the subintimal space within the allograft vessels, resulting in a significant prolongation of graft survival compared with that in the untreated group (67 days vs. 7 days, respectively). These effects were counterbalanced by the administration of an anti-Gr-1, which reduced allograft survival to 21 days. Moreover, adoptive transcoronary arterial transfer of MDSCs from rapamycin-treated recipients prolonged allograft survival; this increase was reversed by the anti-Gr-1 antibody. Finally, co-administration of rapamycin and a mitogen-activated protein kinase kinase (MEK) inhibitor trametinib reversed rapamycin-mediated MDSC recruitment. Thus, the mTOR and Raf/MEK/extracellular signal regulated kinase (ERK) signaling pathways appear to play an important role in MDSC expansion.
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Supervivencia de Injerto/efectos de los fármacos , Trasplante de Corazón , Tolerancia Inmunológica/inmunología , Inmunosupresores/farmacología , Células Mieloides/inmunología , Sirolimus/farmacología , Aloinjertos , Animales , Linfocitos T CD4-Positivos/citología , Linfocitos T CD4-Positivos/inmunología , Citometría de Flujo , Rechazo de Injerto/tratamiento farmacológico , Terapia de Inmunosupresión , Activación de Linfocitos , Ratones , Ratones Endogámicos C3H , Ratones Endogámicos C57BL , Células Mieloides/citología , Óxido Nítrico Sintasa de Tipo II/metabolismo , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
BACKGROUND: The introduction of rituximab has led to a growing tendency to perform ABO-incompatible living-donor kidney transplantation (LDKT) without splenectomy. However, the optimal dosage of rituximab is undefined. METHOD: Fifty-five LDKT recipients who had neither a history of hepatitis B infection nor positive crossmatch were enrolled between October 2005 and June 2014. Recipients were divided into three groups by year of transplantation: 2005 to 2008; 2009 to 2011; and 2012 to 2014. Percentages of CD20-positive B lymphocytes and blood-group antibody titers were monitored before renal transplantation. An initial rituximab dosage of 100 mg/body (for titers below 64) or 200 mg/body (for titers above 128) was administered 2 weeks before transplantation. If the percentage of peripheral B lymphocytes remained greater than 0.5%, additional rituximab (100 mg or 200 mg) was administered. Patient demographics, patient survival, graft survival, and complication rates were compared. RESULTS: Nine patients received rituximab 100 mg/body (low-dose rituximab [LDR] group). Overall survival and graft survival rates did not differ significantly between the LDR group and other cases. The incidences of myelosuppression and viral infection were lower in the LDR group than the other cases. CONCLUSION: A low dose of rituximab (100 mg/body) is adequate in ABO-incompatible LDKT, especially in cases with low blood-type antibody titer against ABO-antigens. Rituximab dosage reduction has been successful in our hospital without serious complications. Moreover, as over-dosage of rituximab may cause myelosuppression, it is reasonable to believe that LDR is a suitable option to safely perform ABO-incompatible LDKT without splenectomy.
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Sistema del Grupo Sanguíneo ABO/inmunología , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Incompatibilidad de Grupos Sanguíneos/inmunología , Rechazo de Injerto/prevención & control , Inmunosupresores/administración & dosificación , Trasplante de Riñón , Donadores Vivos , Adulto , Anciano , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Tipificación y Pruebas Cruzadas Sanguíneas , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Rechazo de Injerto/inmunología , Supervivencia de Injerto/inmunología , Humanos , Inmunosupresores/uso terapéutico , Trasplante de Riñón/mortalidad , Masculino , Persona de Mediana Edad , Rituximab , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: There is a growing tendency to perform pre-emptive kidney transplantation (PKT). However, less research has been performed on outcomes of PKT and kidney transplantation (KT) after long-term dialysis (LD). METHODS: To elucidate advantages of PKT to KTLD, 96 patients who underwent living-donor KT at our university from 2000 to 2011 were enrolled for this study: 64 patients in the PKT0 (0 months dialysis) group; 14 patients in the PKT-3 group (less than 3 months dialysis); 18 patients in the LD (dialysis > 120 months) group. All recipients were assessed for patients' survival, graft survival, urinary tract infection, laboratory data, episodes of acute rejection, cytomegalovirus-related diseases, and other significant infectious diseases which required hospitalization. RESULTS: Although there were no significant differences in 5-year graft survival (93.8% in PKT0, 85.7% in PKT-3, and 83.7% in control), 5-year patient survival is better in the PKT0 group (96.9%) and the PKT-3 group (92.9%) compared to 88.9% in the control group. Urinary tract infection is clearly correlated with the LD group (44.4% in the LD group vs 19.2% in the PKT group) primarily due to atrophic bladder and subsequent vesicoureteral reflux. Slightly higher rates of acute rejection were found in the PKT groups (30.8% vs 26.3%). CONCLUSION: This study revealed that there are both advantages and disadvantages of PKT. It is clear, therefore, that PKT can be recommended for end-stage renal disease patients provided enough attention is paid to the onset of acute rejection.
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Fallo Renal Crónico/cirugía , Trasplante de Riñón/métodos , Adulto , Femenino , Estudios de Seguimiento , Supervivencia de Injerto , Humanos , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/terapia , Donadores Vivos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Diálisis Renal , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Introduction of everolimus (RAD) has been established as a new immunosuppressive medication for kidney transplant (KT) recipients. Administration of RAD is capable of reducing the dosage of coadministrated calcineurin inhibitors (CNI). However, histological investigations have rarely been performed. METHODS: To clarify histopathologic effects of RAD, a total of 9 adult KT recipients were enrolled (RAD group, n = 5; Mycophenolate mofetil (MMF) group, n = 4). Renal graft biopsies had been performed at 3 weeks and 1 year following KT. RESULTS: There were no differences in 1-, 3-, and 5-year graft survival rates (RAD group: 100%, 100%, and 80%, respectively; MMF group: 100%, 100%, and 75%, respectively), and patient survival between the 2 groups (no deaths during the 5 years post-transplantation). Interestingly, although 2 patients in the RAD group had developed CNI nephrotoxicity clinically, renal biopsies had proven no CNI-related lesions 1 year later, which might be due to the reduction in CNI. On the other hand, 1 patient, in the MMF group, had been diagnosed histologically with new-onset CNI nephrotoxicity 1 year following KT. Importantly, the frequency and mean arteriolar hyalinosis (ah) scores, which reflect CNI nephrotoxicity, were significantly higher in the MMF group at 1-year biopsy (P < .05, P < .0001). Two patients in the RAD group improved their ah scores between 3 weeks and 1 year. CONCLUSIONS: Pathological findings revealed that reversible CNI nephrotoxicity can be improved by RAD with reduced CNI maintenance therapy. It is reasonable to believe, therefore, that introduction of RAD is useful for patients who have been diagnosed with CNI nephrotoxicity.
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Rechazo de Injerto/prevención & control , Inmunosupresores/uso terapéutico , Trasplante de Riñón , Riñón/efectos de los fármacos , Sirolimus/análogos & derivados , Adulto , Biopsia , Inhibidores de la Calcineurina/efectos adversos , Inhibidores de la Calcineurina/uso terapéutico , Quimioterapia Combinada , Everolimus , Femenino , Rechazo de Injerto/patología , Humanos , Inmunosupresores/efectos adversos , Riñón/patología , Trasplante de Riñón/mortalidad , Masculino , Persona de Mediana Edad , Ácido Micofenólico/efectos adversos , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapéutico , Estudios Prospectivos , Sirolimus/efectos adversos , Sirolimus/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: Chronic allograft injury (CAI) is one of the most important factors for graft failure after renal transplantation. Protocol biopsy is the most valuable tool for revealing subclinical renal allograft failure. Transient elastography (TE) is a noninvasive technique that has shown utility for the assessment of hepatic and renal fibrosis. This study sought to evaluate whether TE was a viable and effective method for the assessment of renal allograft failure. PATIENTS AND METHODS: Thirty-five patients underwent TE by Fibro Scan (Echosense, Paris, France). Biopsies were performed in 27 patients, allowing classification according to Banff chronic changes in the interstitium grade 0, grade 1 or grade 2. RESULTS: Measurement of parenchymal stiffness was successful in 31 of 35 patients (91%). Stiffness was significantly correlated with interstitial fibrosis (P < .05) and inversely related with estimated glomerular filtration rate (eGFR; P < .05). Stiffness values of patients with eGFR > 50 mL/min were lower than those of patients with eGFR < 50 mL/min (P < .05). Patients classed as CAI Banff grade 0 had significantly less parenchymal stiffness than patients with Banff grade 1 or grade 2 CAI (P < .05). Parenchymal stiffness measured by TE reflected interstitial fibrosis in renal allograft. CONCLUSION: Assessment of parenchymal renal allograft stiffness by TE was effective for identifying patients with CAI who may subsequently benefit from biopsy and modification of the immunosuppressive regimen. Assessment of parenchymal renal allograft stiffness can be effective for identifying patients with CAI. TE has the potential to reduce the number of renal allograft biopsies required for accurate assessment of CAI.
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Aloinjertos/patología , Diagnóstico por Imagen de Elasticidad , Trasplante de Riñón , Riñón/patología , Adulto , Anciano , Aloinjertos/diagnóstico por imagen , Biopsia , Femenino , Fibrosis/diagnóstico por imagen , Humanos , Riñón/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Trasplante HomólogoRESUMEN
BACKGROUND: Due to the shortage of deceased donor kidneys, we have expanded the indications for living-donor kidney transplantation (LKT) including ABO-incompatible (ABO-i) donors in Japan. In this study, the utility of protocol biopsies was discussed in ABO-i LKT. METHODS: Protocol biopsies have been performed on kidney graft 1 hour, 3 weeks, and 1 year after LKT in our institution. The relationship between biopsies and clinical courses was considered retrospectively in 38 cases of ABO-i LKT. The immunosuppressive regimen consisted of anti-CD20 antibody, mycophenolate mofetil, prednisolone, calcineurin inhibitor (cyclosporine or tacrolimus), and anti-CD25 antibody. Anti-ABO blood type antibody removal by plasmapheresis was performed before LKT up to 32 times. The post-transplantation regimen consisted of mycophenolate mofetil or mizoribine as an antimetabolite. RESULTS: Episode biopsies have been performed in 6 cases within 3 weeks post-transplantation. Each pathological diagnosis was as follows: antibody-mediated rejection (AMR; 5 cases) and calcineurin inhibitor (CNI) nephrotoxicity (1 case). Subclinical chronic active AMR was found at 1 year post-transplantation follow-up biopsies in 4 of the 6 cases. Episode biopsies have been done in the other 6 cases from 1 month to 1 year post-transplantation. Each pathological diagnosis was as follows: acute T-cell-mediated rejection (TMR; 1 case), vesicoureteral reflux (VUR; 3 cases), CNI nephrotoxicity (2 cases), and VUR + CNI nephrotoxicity (1 case). AMR was also not found at 1 year post-transplantation follow-up biopsies in them. In all cases episode biopsies were performed based on pathological diagnosis and had no graft dysfunction after that. CONCLUSIONS: Pathological study revealed that acute AMR was found early (ie, within 3 weeks) following transplantation. Although appropriate treatment made AMR go into remission once, chronic active AMR was often found at 1-year follow-up biopsies.
Asunto(s)
Sistema del Grupo Sanguíneo ABO , Trasplante de Riñón , Adulto , Biopsia , Femenino , Estudios de Seguimiento , Humanos , Inmunosupresores/administración & dosificación , Japón , Riñón/patología , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Mizoribine (MZR) has been developed as an immunosuppressive agent in Japan, but has a less potent immunosuppressive effect up to 3 mg/kg/d. We previously reported that high-dose MZR, at 6 mg/kg/d, would be effective and safe for ABO-incompatible(ABO-i) living donor kidney transplantation (LDKT) patients when combined with cyclosporine (CsA) or tacrolimus(FK), anti-CD20 and anti-CD25 monoclonal antibodies, and corticosteroid without splenectomy in a 1-year study. Therefore, we observed these patients for 3 years. METHODS: From 2007 to 2010, we encountered 24 cases of ABO-i LDKT using anti-CD20 and anti-CD25 monoclonal antibodies without splenectomy. The pretransplantation immunosuppressive regimen consisted of two doses of anti-CD20 antibody, mycophenolate mofetil (MMF, 25 mg/kg/d), prednisolone, calcineurin inhibitor (CNI; CsA 7 mg/kg or (FK 0.2 mg/kg) and two doses of anti-CD25 antibody. Antibody removal by plasmapheresis was performed before LDKT up to several times according to the antibody titer. The post-transplantation regimen consisted of high-dose MZR (6 mg/kg/d) instead of MMF (MZR group, N = 12) . RESULTS: The 3-year graft survival rates for the MZR and MMF groups were 91.7% and 100%, respectively. Serum creatinine levels for the MZR and MMF groups were 1.44 mg/dL and 1.31 mg/dL at 1 year, 1.55 mg/dL and 1.41 mg/dL at 2 years, and 1.51 mg/dL and 1.48 mg/dL at 3 years, respectively (not significant [NS]). The MZR group did not show a higher rate of elevated serum uric acid values. The percentage of patients who were administered anti-uric medication was 42.5% (5/12) in the MZR group and 50% (6/12) in the MMF group (P = NS) at the third year. Severe infection, such as cytomegalovirus, herpes zoster, was not observed at the second and third years in both groups. CONCLUSION: A high-dose MZR regimen including CNI (CsA or FK), steroid, and anti-CD20 and anti-CD25 antibodies without splenectomy was effective and safe in ABO-i renal transplantation.
Asunto(s)
Sistema del Grupo Sanguíneo ABO , Anticuerpos Monoclonales/uso terapéutico , Antígenos CD20/inmunología , Inmunosupresores/uso terapéutico , Subunidad alfa del Receptor de Interleucina-2/inmunología , Trasplante de Riñón , Ribonucleósidos/uso terapéutico , Creatinina/sangre , Relación Dosis-Respuesta a Droga , Humanos , Inmunosupresores/administración & dosificación , Inmunosupresores/efectos adversos , Ribonucleósidos/administración & dosificación , Ribonucleósidos/efectos adversos , EsplenectomíaRESUMEN
In Japan, diabetic nephropathy accounted for 16,225 (43.7%) of the 38,473 patients who began hemodialysis in 2010 and the number increases year by year. In 1991, we started a kidney transplantation program for patients with diabetic nephropathy in our institution, and the ratio of patients who underwent kidney transplantation for diabetic nephropathy traces the course of increase. Among the 516 patients who underwent primary kidney transplantation in our institution from January 1991 to February 2013, we divided them into 2 groups. One group was the diabetes mellitus (DM) group, which included patients with primary disease of diabetic nephropathy, and the other group was the non-DM group. The DM group included 50 patients, and in our institution the ratio traces the course to increase. There was no significant difference for the 1-year and 5-year patient survival rates and graft survival rates between the DM group and the non-DM group. Moreover, the rate of acute rejection in the 2 groups was not significantly different. Furthermore, when we investigated the causes of death in the 2 groups, there was no significant difference with the mortality of cases due to heart vascular disease in the DM group and the non-DM group. Also, no case in which the graft lost function due to recurrence of diabetic nephropathy was observed. Although the early outcome of kidney transplantation for diabetic nephropathy in our institution did not have inferiority in comparison with kidney transplantation for the other primary disease, we think that careful diabetic control after kidney transplantation is required for long-term outcome.
Asunto(s)
Nefropatías Diabéticas/cirugía , Trasplante de Riñón , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tasa de SupervivenciaRESUMEN
BACKGROUND: Renal cancers commonly occur in the native kidneys of renal transplant recipients, whereas renal cancer in the grafted kidney has been reported occasionally. Renal cancer in the grafted kidney occurred 16 years after graft loss in this case, which would be a more rare case. CASE REPORT: A 60-year-old man who had a kidney transplant from his mother at the age of 31 years and had hemodialysis again because of chronic rejection from the age of 44 years had right lower abdominal pain. Computerized tomography (CT) showed tumor involvement in the grafted kidney. Positron-emission tomography-CT also showed hot spots in the liver, cervical vertebra, and costal bone. Needle biopsy for grafted kidney and liver tumors were done, and pathologic findings revealed renal cancer of grafted kidney and metastatic liver tumor. Graftectomy was done, and renal cancer was diagnosed as spindle cell carcinoma. Irradiation for cervical bone metastasis was done after the surgery. He complained of abdominal pain and eating disturbance 2 months after the surgery. CT showed a huge recurrence tumor and multiple tumor dissemination. Small intestine was involved and obstructed by the main tumor. He died of recurrence of renal cancer 3 months after the surgery. CONCLUSIONS: It is reported that the rate of renal cell carcinoma in the grafted kidney was 0.19%-0.5% and it occurred at a mean of 12.6 years after renal transplantation. Herein, we report a rare case of renal cancer that occurred 29 years after renal transplantation. Long-term observation should be required for recipients who had rehemodialysis.