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1.
Tech Coloproctol ; 23(10): 973-980, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31535238

RESUMEN

BACKGROUND: Anastomotic leakage (AL) is one of the most troublesome complications in colorectal surgery. Recently, near-infrared fluorescence (NIRF) imaging has been used intraoperatively to detect sentinel lymph nodes and visualize the blood supply at the region of interest (ROI). The aim of this study was to evaluate the role of visualization and quantification of bowel perfusion around the anastomosis using NIRF system in predicting AL. METHODS: A prospective study was conducted on patients who had laparoscopic surgery for colorectal cancer at our institution. Perfusion of the anastomosis was evaluated with NIRF imaging after intravenous injection of indocyanine green (ICG). The time course of fluorescence intensity was recorded by an imaging analyzer We measured the time from ICG injection to the beginning of fluorescence (T0), maximum intensity (Imax), time to reach Imax (Tmax), time to reach Imax 50% ([Formula: see text]) and slope (S) after the anastomosis. RESULTS: Tumor locations were as follows; cecum: 2, ascending colon: 2, transverse colon: 7, descending colon: 1, sigmoid colon: 2, rectosigmoid colon: 3 and rectum: 6 (one case with synchronous cancer). All operations were performed laparoscopically. Four patients were diagnosed with or suspected to have AL (2 patients with grade B anastomotic leakage after low anterior resection, 1 patient with minor leakage in transverse colon resection and 1 patient needing re-anastomosis intraoperatively in transverse colon resection). T0 was significantly longer in the AL group than in patients without AL (64.3 ± 27.6 and 18.2 ± 6.6 s, p = 2.2 × 10-3). CONCLUSIONS: Perfusion of the anastomosis could be successfully visualized and quantified using NIRF imaging with ICG. T0 might be a useful parameter for prediction of AL.


Asunto(s)
Fuga Anastomótica/diagnóstico por imagen , Neoplasias Colorrectales/cirugía , Cuidados Intraoperatorios/métodos , Imagen de Perfusión/métodos , Estomas Quirúrgicos/irrigación sanguínea , Anciano , Anciano de 80 o más Años , Anastomosis Quirúrgica/efectos adversos , Anastomosis Quirúrgica/métodos , Fuga Anastomótica/etiología , Colectomía/efectos adversos , Colectomía/métodos , Colon/irrigación sanguínea , Colon/diagnóstico por imagen , Colon/cirugía , Colorantes , Femenino , Fluorescencia , Humanos , Verde de Indocianina , Rayos Infrarrojos , Laparoscopía/efectos adversos , Laparoscopía/métodos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Recto/irrigación sanguínea , Recto/diagnóstico por imagen , Recto/cirugía , Estomas Quirúrgicos/efectos adversos
3.
Org Biomol Chem ; 15(2): 285-300, 2017 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-27906394

RESUMEN

This review describes recent advances in direct borylation reactions of organic halides, including both transition-metal-catalyzed and metal-free methods. Since the pioneering work on palladium-catalyzed boryl substitution of aryl halides with a diboron compound reported by Miyaura and co-workers in 1995, various catalytic systems for the borylation of aryl, alkneyl, and alkyl halides have been developed to give a wide range of organoboronate esters that cannot be synthesized using conventional methods. Borylative cyclization of alkyl halides is also discussed.

4.
J Physiol ; 592(17): 3859-80, 2014 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-25015920

RESUMEN

Controlled mechanical ventilation (CMV) plays a key role in triggering the impaired diaphragm muscle function and the concomitant delayed weaning from the respirator in critically ill intensive care unit (ICU) patients. To date, experimental and clinical studies have primarily focused on early effects on the diaphragm by CMV, or at specific time points. To improve our understanding of the mechanisms underlying the impaired diaphragm muscle function in response to mechanical ventilation, we have performed time-resolved analyses between 6 h and 14 days using an experimental rat ICU model allowing detailed studies of the diaphragm in response to long-term CMV. A rapid and early decline in maximum muscle fibre force and preceding muscle fibre atrophy was observed in the diaphragm in response to CMV, resulting in an 85% reduction in residual diaphragm fibre function after 9-14 days of CMV. A modest loss of contractile proteins was observed and linked to an early activation of the ubiquitin proteasome pathway, myosin:actin ratios were not affected and the transcriptional regulation of myosin isoforms did not show any dramatic changes during the observation period. Furthermore, small angle X-ray diffraction analyses demonstrate that myosin can bind to actin in an ATP-dependent manner even after 9-14 days of exposure to CMV. Thus, quantitative changes in muscle fibre size and contractile proteins are not the dominating factors underlying the dramatic decline in diaphragm muscle function in response to CMV, in contrast to earlier observations in limb muscles. The observed early loss of subsarcolemmal neuronal nitric oxide synthase activity, onset of oxidative stress, intracellular lipid accumulation and post-translational protein modifications strongly argue for significant qualitative changes in contractile proteins causing the severely impaired residual function in diaphragm fibres after long-term mechanical ventilation. For the first time, the present study demonstrates novel changes in the diaphragm structure/function and underlying mechanisms at the gene, protein and cellular levels in response to CMV at a high temporal resolution ranging from 6 h to 14 days.


Asunto(s)
Diafragma/fisiopatología , Contracción Muscular , Fibras Musculares Esqueléticas/metabolismo , Ventilación Pulmonar , Ventiladores Mecánicos/efectos adversos , Actinas/genética , Actinas/metabolismo , Adenosina Trifosfato/metabolismo , Animales , Diafragma/citología , Diafragma/metabolismo , Femenino , Metabolismo de los Lípidos , Fibras Musculares Esqueléticas/fisiología , Fuerza Muscular , Miosinas/genética , Miosinas/metabolismo , Óxido Nítrico Sintasa de Tipo I/genética , Óxido Nítrico Sintasa de Tipo I/metabolismo , Estrés Oxidativo , Complejo de la Endopetidasa Proteasomal/metabolismo , Ratas , Ratas Sprague-Dawley , Factores de Tiempo
6.
Pharmazie ; 67(5): 384-8, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-22764568

RESUMEN

The characteristics of intestinal absorption of quinidine, a P-glycoprotein (P-gp) substrate in biopharmaceutics classification system (BCS) Class I, after oral administration as a powder in No. 9 HPMC capsule (diameter 2.6 mm; length 8.4 mm, volume 25 microl) was examined in rats from the following viewpoints: (i) main absorption site of quinidine, (ii) effect of dosage amounts (or luminal concentrations) of quinidine (10 mg vs 0.1 mg/kg), (iii) contribution of P-gp in quinidine absorption (0.1 mg/kg), and (iv) effect of gastric pH on quinidine absorption. Quinidine administered orally at a dose of 10 mg/kg was discharged from the stomach steadily with time and disappeared rapidly from the proximal intestine, where P-gp expression was low. In contrast, quinidine administered at a dose of 0.1 mg/kg remained longer in the gastrointestinal lumen than that administered at a dose of 10 mg/kg. The pretreatment with cyclosporine A, a P-gp inhibitor, greatly increased the intestinal absorption of quinidine given at a dose of 0.1 mg/kg. The gastric pH in untreated control rats was pH 3.6, and the treatment with ranitidine (10mg/kg, ip), a H2 blocker, increased to pH 6.4. The recovered amounts of quinidine 30 min after administration were 21.1% of dose in control rats and 94.7% in ranitidine-treated rats. The value of plasma AUC(0-6h) of quinidine in ranitidine-treated rats was about 40% that in untreated control rats. In conclusion, quinidine was rapidly and efficiently absorbed at the proximal intestine under ordinary circumstances. However, the oral bioavailability was modulated by various factors including the dose (or luminal concentration at the absorption site), presence of P-gp inhibitors, and gastrointestinal pH.


Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Antimaláricos/farmacocinética , Quinidina/farmacocinética , Análisis de Varianza , Animales , Antimaláricos/administración & dosificación , Disponibilidad Biológica , Cromatografía Líquida de Alta Presión , Dextranos , Fluoresceína-5-Isotiocianato/análogos & derivados , Ácido Gástrico/metabolismo , Concentración de Iones de Hidrógeno , Indicadores y Reactivos , Absorción Intestinal , Mucosa Intestinal/metabolismo , Masculino , Peso Molecular , Polvos , Quinidina/administración & dosificación , Ratas , Ratas Sprague-Dawley
7.
ESMO Open ; 7(6): 100591, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36208496

RESUMEN

BACKGROUND: A growing body of evidence suggests that non-viral hepatocellular carcinoma (HCC) might benefit less from immunotherapy. MATERIALS AND METHODS: We carried out a retrospective analysis of prospectively collected data from consecutive patients with non-viral advanced HCC, treated with atezolizumab plus bevacizumab, lenvatinib, or sorafenib, in 36 centers in 4 countries (Italy, Japan, Republic of Korea, and UK). The primary endpoint was overall survival (OS) with atezolizumab plus bevacizumab versus lenvatinib. Secondary endpoints were progression-free survival (PFS) with atezolizumab plus bevacizumab versus lenvatinib, and OS and PFS with atezolizumab plus bevacizumab versus sorafenib. For the primary and secondary endpoints, we carried out the analysis on the whole population first, and then we divided the cohort into two groups: non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) population and non-NAFLD/NASH population. RESULTS: One hundred and ninety patients received atezolizumab plus bevacizumab, 569 patients received lenvatinib, and 210 patients received sorafenib. In the whole population, multivariate analysis showed that treatment with lenvatinib was associated with a longer OS [hazard ratio (HR) 0.65; 95% confidence interval (CI) 0.44-0.95; P = 0.0268] and PFS (HR 0.67; 95% CI 0.51-0.86; P = 0.002) compared to atezolizumab plus bevacizumab. In the NAFLD/NASH population, multivariate analysis confirmed that lenvatinib treatment was associated with a longer OS (HR 0.46; 95% CI 0.26-0.84; P = 0.0110) and PFS (HR 0.55; 95% CI 0.38-0.82; P = 0.031) compared to atezolizumab plus bevacizumab. In the subgroup of non-NAFLD/NASH patients, no difference in OS or PFS was observed between patients treated with lenvatinib and those treated with atezolizumab plus bevacizumab. All these results were confirmed following propensity score matching analysis. By comparing patients receiving atezolizumab plus bevacizumab versus sorafenib, no statistically significant difference in survival was observed. CONCLUSIONS: The present analysis conducted on a large number of advanced non-viral HCC patients showed for the first time that treatment with lenvatinib is associated with a significant survival benefit compared to atezolizumab plus bevacizumab, in particular in patients with NAFLD/NASH-related HCC.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Enfermedad del Hígado Graso no Alcohólico , Humanos , Sorafenib/farmacología , Sorafenib/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Bevacizumab/farmacología , Bevacizumab/uso terapéutico , Puntaje de Propensión , Estudios Retrospectivos , Neoplasias Hepáticas/tratamiento farmacológico
8.
ESMO Open ; 6(1): 100020, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33399083

RESUMEN

BACKGROUND: The immunological inflammatory biomarkers for advanced hepatocellular carcinoma are unclear. We aimed to investigate the association of immunity and inflammatory status with treatment outcomes in patients with advanced hepatocellular carcinoma who received molecular-targeted agents as primary treatment. PATIENTS AND METHODS: We enrolled 728 consecutive patients with advanced hepatocellular carcinoma who received sorafenib (n = 554) or lenvatinib (n = 174) as primary treatment in Japan between May 2009 and June 2020. Changes in the neutrophil-to-lymphocyte ratio before and 1 month after treatment and their impact on survival were evaluated. The cut-off values of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio for predicting overall and progression-free survival were calculated using receiver operating characteristic curves. RESULTS: The neutrophil-to-lymphocyte ratio, but not the platelet-to-lymphocyte ratio, was an independent prognostic factor. Patients with decreased neutrophil-to-lymphocyte ratio survived significantly longer than patients with increased neutrophil-to-lymphocyte ratio (median overall survival: 14.7 versus 10.4 months, P = 0.0110). Among patients with a low pre-treatment neutrophil-to-lymphocyte ratio, the overall survival did not differ significantly between those with decreased and those with increased neutrophil-to-lymphocyte ratio after 1 month (median: 19.0 versus 14.8 months, P = 0.1498). However, among patients with high pre-treatment neutrophil-to-lymphocyte ratio, those whose neutrophil-to-lymphocyte ratio decreased after 1 month showed significantly longer survival than those whose neutrophil-to-lymphocyte ratio increased (median: 12.7 versus 5.5 months, P < 0.0001). The therapeutic effect was not correlated with pre-treatment neutrophil-to-lymphocyte ratio or platelet-to-lymphocyte ratio. CONCLUSIONS: The neutrophil-to-lymphocyte ratio is a prognostic factor, along with liver function and tumor markers, in patients with advanced hepatocellular carcinoma who received molecular-targeted agents as primary treatment. Thus, the neutrophil-to-lymphocyte ratio could be a prognostic biomarker for advanced hepatocellular carcinoma primarily treated with immunotherapy.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomarcadores de Tumor , Carcinoma Hepatocelular/tratamiento farmacológico , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Linfocitos , Pronóstico
9.
ESMO Open ; 6(6): 100330, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34847382

RESUMEN

BACKGROUND: Hepatocellular carcinoma (HCC) treatment remains a big challenge in the field of oncology. The liver disease (viral or not viral) underlying HCC turned out to be crucial in determining the biologic behavior of the tumor, including its response to treatment. The aim of this analysis was to investigate the role of the etiology of the underlying liver disease in survival outcomes. PATIENTS AND METHODS: We conducted a multicenter retrospective study on a large cohort of patients treated with lenvatinib as first-line therapy for advanced HCC from both Eastern and Western institutions. Univariate and multivariate analyses were performed. RESULTS: Among the 1232 lenvatinib-treated HCC patients, 453 (36.8%) were hepatitis C virus positive, 268 hepatitis B virus positive (21.8%), 236 nonalcoholic steatohepatitis (NASH) correlate (19.2%) and 275 had other etiologies (22.3%). The median progression-free survival (mPFS) was 6.2 months [95% confidence interval (CI) 5.9-6.7 months] and the median overall survival (mOS) was 15.8 months (95% CI 14.9-17.2 months). In the univariate analysis for OS NASH-HCC was associated with longer mOS [22.2 versus 15.1 months; hazard ratio (HR) 0.69; 95% CI 0.56-0.85; P = 0.0006]. In the univariate analysis for PFS NASH-HCC was associated with longer mPFS (7.5 versus 6.5 months; HR 0.84; 95% CI 0.71-0.99; P = 0.0436). The multivariate analysis confirmed NASH-HCC (HR 0.64; 95% CI 0.48-0.86; P = 0.0028) as an independent prognostic factor for OS, along with albumin-bilirubin (ALBI) grade, extrahepatic spread, neutrophil-to-lymphocyte ratio, portal vein thrombosis, Eastern Cooperative Oncology Group (ECOG) performance status and alpha-fetoprotein. An interaction test was performed between sorafenib and lenvatinib cohorts and the results highlighted the positive predictive role of NASH in favor of the lenvatinib arm (P = 0.0047). CONCLUSION: NASH has been identified as an independent prognostic factor in a large cohort of patients with advanced HCC treated with lenvatinib, thereby suggesting the role of the etiology in the selection of patients for tyrosine kinase treatment. If validated, this result could provide new insights useful to improve the management of these patients.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Enfermedad del Hígado Graso no Alcohólico , Carcinoma Hepatocelular/tratamiento farmacológico , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Compuestos de Fenilurea , Pronóstico , Quinolinas , Estudios Retrospectivos
10.
Clin Exp Allergy ; 39(2): 290-8, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19032358

RESUMEN

BACKGROUND: We previously reported a mouse model of bronchial asthma showing eosinophilic inflammation, but not airway hyperresponsiveness (AHR), after prolonged antigen exposure. This model showed an increase of IL-12 in the lung. OBJECTIVE: The aim of this study was to investigate the role of IL-12p40 in a murine asthma model with prolonged antigen exposures. METHODS: An ovalbumin (OVA)-induced asthma model was first established in wild-type (WT) and IL-12p40-deficient (IL-12p40(-/-)) mice. Both strains of mice were further exposed to either OVA (prolonged exposure group) or phosphate-buffered saline (positive control group) 3 days per week for 3 weeks. During week 4, both groups of mice were given a final challenge with OVA. RESULTS: Prolonged antigen exposures resulted in marked suppression of airway eosinophilia in both WT and IL-12p40(-/-) mice. However, AHR persisted in IL-12p40(-/-) but not in WT mice. There were no significant differences of IL-5, IL-13 or IFN-gamma levels in bronchoalveolar lavage fluid between WT and IL-12p40(-/-) mice. The hydroxyproline content of the lung and peribronchial fibrosis were, however, significantly increased in IL-12p40(-/-) mice. CONCLUSION: The results suggest that endogenous IL-12p40 is essential for inhibition of AHR and peribronchial fibrosis, but not eosinophilic inflammation, in a murine asthma model with prolonged antigen exposures.


Asunto(s)
Asma/inmunología , Hiperreactividad Bronquial/inmunología , Regulación hacia Abajo/inmunología , Tolerancia Inmunológica/fisiología , Subunidad p40 de la Interleucina-12/fisiología , Ovalbúmina/administración & dosificación , Administración por Inhalación , Animales , Asma/metabolismo , Asma/patología , Asma/fisiopatología , Hiperreactividad Bronquial/fisiopatología , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Citocinas/análisis , Citocinas/metabolismo , Modelos Animales de Enfermedad , Eosinófilos/citología , Femenino , Leucocitos/citología , Pulmón/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ovalbúmina/inmunología , Pruebas de Función Respiratoria
11.
Meat Sci ; 82(3): 300-8, 2009 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-20416730

RESUMEN

The development of different muscles and adipose tissues during growth was investigated in commercial Japanese Black (JB) cattle and compared with breeds of the largest variation to be found in Europe. Animals, reared under typical conditions for Japanese and European beef production systems, gained similar body weights but different carcass composition at 24months of age. The carcass of JB contained more adipose tissue and the least proportion of muscle. The longissimus muscle of JB developed extraordinary amounts of 23.3% intramuscular fat (IMF) at 24months of age, compared from 0.6% to 4.7% in European breeds. The relationships between IMF content in the longissimus muscle and different adipose tissue weights indicate that a large amount of "waste fat" is accreted with every percent of IMF. However in JB, the good ability of IMF deposition is associated with relatively least development of "waste fat", as a result of unique breed characteristics combined with special feeding system.

12.
Br Poult Sci ; 50(1): 47-56, 2009 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19234929

RESUMEN

1. Varying growth rates in chickens were induced by different nutritional regimes. The collagen content and architecture of iliotibialis lateralis (ITL) muscle were compared among 21-d-old chick types and broiler types at 80 or 95 d of age. 2. Relative size of ITL muscle was greater in the rapid growing (1.16% of live weight) than the slow growing chicks (1.02% of live weight). The 80-d-old broilers with a compensatory growth phase after an earlier slow growth period produced ITL muscle at 1.65-1.69% of live weight. The ITL muscle in 80- and 95-d-old broilers with restricted later growth after an earlier rapid growth period was 1.29 and 1.49% of live weight, respectively. 3. Collagen content of ITL muscle did not differ between chick types and also among the broiler types. However, collagen concentration decreased from 6.00-6.51 mg/g in the chicks to 3.33-4.00 mg/g in the broilers. 4. Thick and thin perimysia and honeycomb endomysia were viewed by scanning electron microscope (SEM) photography. In the perimysia, a central wide layer of longitudinal collagen fibres and peripheral narrow band of transverse fibres were distinguished. Collagen baskets of adipocytes were observed in the perimysia. 5. Perimysial collagen fibres markedly increased in number and formed a larger fibre cluster during growth from chicks to broilers. Endomysia changed from thin to thicker meshwork with growth. However, the collagen architecture of the muscle in broilers did not change under different nutritional regimes. 6. In conclusion, ITL muscle of chicken develops optimally when body growth is enhanced, but the collagen content and architecture in broilers are not affected by different growth processes.


Asunto(s)
Fenómenos Fisiológicos Nutricionales de los Animales/fisiología , Pollos/fisiología , Colágeno/metabolismo , Músculo Esquelético/fisiología , Animales , Peso Corporal/fisiología , Pollos/crecimiento & desarrollo , Pollos/metabolismo , Femenino , Histocitoquímica/veterinaria , Masculino , Microscopía Electrónica de Rastreo/veterinaria , Músculo Esquelético/crecimiento & desarrollo , Músculo Esquelético/metabolismo , Tamaño de los Órganos/fisiología
13.
Br Poult Sci ; 50(4): 424-35, 2009 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-19735011

RESUMEN

1. Various growth rates of chickens were induced with different nutritional regimes, and the collagen content and architecture of the medial part of the puboischiofemoralis muscle were compared among 21-d-old chicks and 80- or 95-d-old broilers. 2. The percentage muscle weight relative to live weight increased from chicks to 80-d-old broilers and the 95-d-old broilers attained the largest percentage. An inter-relationship of the percentage muscle weight and the growth rates of birds could not be determined. 3. Collagen concentration was related to the growth rates for the first 21 d post hatching and maintained the same level during the later stages up to 80 d. The 95-d-old broilers, that were subjected to early rapid growth followed by restricted later growth, had the highest collagen content. 4. On SEM (Scanning Electron Microscopy) photographs, endomysial honeycombs were small and encircled by perimysia of a collagen network with small mesh size. Thin and thick perimysia were distinguished and the expanded portion of thick perimysia was also observed. Generally, the perimysia were made up of rough collagen tissue where fatty tissue developed, especially in the broilers. 5. Perimysial collagen fibres with mainly transverse striation were divided into two fundamental types, wide collagen platelets and narrow cords. With growth from the chick to broiler stage, features of the collagen fibres did not change regardless of expansion of the thick perimysia. Endomysia increased slightly from thin to thick meshwork as growth progressed. However, the collagen architecture of the muscle in broilers did not change under different nutritional regimes. 6. In conclusion, the puboischiofemoralis muscle of chickens develops relative to live weight when later growth is limited in broilers, but the collagen architecture is not affected by the different growth rates.


Asunto(s)
Pollos/crecimiento & desarrollo , Pollos/metabolismo , Colágeno/análisis , Dieta , Músculo Esquelético/química , Alimentación Animal , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Peso Corporal , Pollos/anatomía & histología , Colágeno/ultraestructura , Inmunohistoquímica , Masculino , Microscopía Electrónica de Rastreo , Músculo Esquelético/ultraestructura , Tamaño de los Órganos
14.
Transplant Proc ; 40(7): 2240-2, 2008 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-18790203

RESUMEN

The clinical efficacy of calcineurin inhibitors administered to renal transplant recipients is considered to be a strong function of the area under the concentration time curve (AUC). Monitoring of blood concentrations for two similar calcineurin inhibitors, cyclosporine (CyA) and tacrolimus (TAC) are different. Namely, CyA blood concentration is usually monitored at two hours after administration (C2), a surrogate for peak concentration (Cp), and TAC at trough concentration (Ct). We examined the behavior of blood concentration curves simultaneously for both CyA and TAC in renal transplant recipients with similar clinical backgrounds. Furthermore, we analyzed the correlation of Cp and Ct vs AUC implementing an area under the trough level, or area above the trough level as new pharmacokinetic parameters, so that C2 for CyA and Ct for TAC has validated using controlled clinical data. We observed differences in the pharmacokinetics between.


Asunto(s)
Ciclosporina/farmacocinética , Trasplante de Riñón/inmunología , Tacrolimus/farmacocinética , Adulto , Área Bajo la Curva , Ciclosporina/sangre , Ciclosporina/uso terapéutico , Relación Dosis-Respuesta a Droga , Monitoreo de Drogas/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tacrolimus/sangre , Tacrolimus/uso terapéutico
15.
Transplant Proc ; 40(8): 2497-500, 2008 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-18929778

RESUMEN

Living donor liver transplantation (LDLT) offers timely transplantation for patients with hepatocellular carcinoma (HCC). If ABO-incompatible LDLT is feasible, the need for pretransplantation treatment may be eliminated, which may reduce overall morbidity. In this article, we have described 8 adult HCC patients who successfully underwent LDLT from ABO-incompatible donors. Antirejection therapy included multiple preoperative plasmaphereses, splenectomy, and an immunosuppressive regimen with tacrolimus, methylprednisolone, and mycophenolate mofetil. The maintenance dose of immunosuppression did not differ from that of the ABO-identical cases. In addition, we also performed intrahepatic arterial infusion of prostaglandin E1. In 5 patients, we administered a single dose of rituximab, a chimeric CD20 monoclonal antibody. As a result of this treatment, 6/8 patients are still alive. Our experience has shown that it is possible to control antibody-mediated humoral rejection and other complications in adult ABO-incompatible LDLT.


Asunto(s)
Sistema del Grupo Sanguíneo ABO , Incompatibilidad de Grupos Sanguíneos , Carcinoma Hepatocelular/cirugía , Inmunosupresores/uso terapéutico , Neoplasias Hepáticas/cirugía , Trasplante de Hígado/inmunología , Donadores Vivos , Adulto , Quimioterapia Combinada , Rechazo de Injerto/prevención & control , Hepatitis B/cirugía , Hepatitis C/cirugía , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Trasplante de Hígado/mortalidad , Persona de Mediana Edad , Estadificación de Neoplasias , Plasmaféresis , Esplenectomía , Análisis de Supervivencia , Sobrevivientes , Resultado del Tratamiento
16.
Transplant Proc ; 40(8): 2539-41, 2008 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-18929794

RESUMEN

OBJECTIVE: The incidence of biliary complications after adult living donor liver transplantation (ALDLT) are still high even though various devices have been reported to overcome them. METHOD: From October 2000 to April 2007, we performed 52 ALDLTs which included 15 ABO-incompatible grafts. Median follow-up was 565 days. In 49 procedures, we used duct-to-duct anastmosis with a stent inserted in the recipient duct and out through the common bile duct wall as an external stent, and in 3 procedures, we used duct-to-jejunostomy anastomosis. We investigated postoperative biliary complications and their management. RESULTS: Forty-four patients received right lobe grafts and 8 received left lobe grafts. Among patients in whom duct-to-duct anastomosis was used, nine (20.5%) developed biliary complications including bile leakage in five and biliary strictures in four. All bile leakage was treated with reoperation. Three biliary strictures were treated with stent placement, and one biliary stricture was treated with magnetic compression anastomosis. Among the three patients in whom duct-to-jejunostomy was used, two (66.7%) had bile leakage and stricture, respectively. Two of four ABO-incompatible patients (50%) had hepatic artery thrombosis with biliary complications, a high incidence. CONCLUSION: In our series of ABO-incompatible patients undergoing ALDLT, those who developed hepatic artery thrombosis exhibited a high incidence of biliary complications.


Asunto(s)
Enfermedades de la Vesícula Biliar/epidemiología , Trasplante de Hígado/efectos adversos , Donadores Vivos , Adulto , Anciano , Anastomosis Quirúrgica , Conductos Biliares/cirugía , Incompatibilidad de Grupos Sanguíneos , Femenino , Humanos , Yeyuno/cirugía , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Procedimientos de Cirugía Plástica , Estudios Retrospectivos , Stents , Resultado del Tratamiento
17.
Transplant Proc ; 40(7): 2104-7, 2008 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-18790165

RESUMEN

BACKGROUND: In Japan, living donor renal transplantation has gained momentum due to an increased number of patients with end-stage renal disease. Living donation not only provides better outcomes, but also the recipients usually need less medications, thereby increasing the quality of life and reducing the potential side effects of immunosuppression. MATERIALS AND METHODS: For the past 25 years, our center had performed 140 open donor nephrectomy (OPNx) renal transplantations. Since July 2003, we changed our procurement operation to living hand-assisted laparoscopic donor nephrectomy (HALNx) in 49 cases. Our operative technique consisted of two 12-mm ports placed in the midaxillary line at the superior and inferior levels of the umbilicus. Next, a 5-cm incision was made in the midline periumbilicus and the hand port system fitted through a midline abdominal incision. RESULTS: In 49 cases, HALNx was completed successfully; no patient required conversion to laparotomy. The estimated blood loss was 33.0 +/- 43.4 g and no patient required blood transfusion. In comparison, in OPNx the blood loss was 426.5 +/- 247.6 g (P < .001). The mean operative times were 167.4 +/- 39.7 minutes for HALNx and 228.4 +/- 35.7 minutes for OPNx (P < .001). The postoperative hospital stays were 9.1 +/- 3.8 days for HALNx and 13.0 +/- 1.9 days for OPNx (P < .001). For 3 years prior to introduction of HALNx, we had performed only 10 living donor renal transplantations. Since the introduction of HALNx in 2003, the number of living donors has tripled during the following 3 years. CONCLUSIONS: Herein we have reported that HALNx was superior in terms of less operative time and blood loss, postoperative pain and recovery, and shorter hospital stay. Overall donor patient satisfaction was also better in the HALNx group. HALNx is a safe procedure that makes kidney donation more appealing to potential live donors and has increased the living donor pool at our center.


Asunto(s)
Trasplante de Riñón/estadística & datos numéricos , Riñón , Donadores Vivos/estadística & datos numéricos , Recolección de Tejidos y Órganos/estadística & datos numéricos , Adulto , Cadáver , Familia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nefrectomía/métodos , Donantes de Tejidos/estadística & datos numéricos , Recolección de Tejidos y Órganos/métodos
18.
Transplant Proc ; 50(8): 2404-2411, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30316367

RESUMEN

BACKGROUND: To increase the number of cadaveric kidney transplants in Japan, it is necessary to proactively use organs from all donors. Since the revision of the Organ Transplant Law, the number of organ donors after cardiac death (DCD) has decreased but the number of organ donors after brain death (DBD) has increased; however, the number of donor organs and awareness of cadaveric transplantation have increased. METHODS: At our institution, 28 patients underwent cadaveric kidney transplantation from January 2001 to December 2016. These patients were classified into 2 groups according to DBD or DCD. Furthermore, 10 patients received transplants from expanded criteria donors (ECD) and 18 received them from standard criteria donors (SCD). RESULTS: Kidney graft survival and engraftment were observed for all patients. There were no significant differences in renal function at 6 months for DBD and DCD transplant recipients. Renal function at 1, 3, and 5 years and serum creatinine levels were better for the ECD group. Renal function at 5 years after transplantation was significantly better for the SCD group than for the ECD group; however, there was no difference in delayed graft function between the SCD and ECD groups. Comparisons of the 3 groups showed good renal function for transplants from DBDs, but there was no significant difference in survival rates. CONCLUSIONS: Results were good for all patients. There were no significant differences in outcomes of our patients who received transplants from ECD or SCD.


Asunto(s)
Muerte Encefálica , Muerte , Trasplante de Riñón/métodos , Donantes de Tejidos , Adulto , Funcionamiento Retardado del Injerto/etiología , Femenino , Supervivencia de Injerto , Humanos , Japón , Trasplante de Riñón/efectos adversos , Trasplante de Riñón/mortalidad , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia , Donantes de Tejidos/provisión & distribución , Trasplante Homólogo
19.
Transplant Proc ; 50(8): 2531-2534, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30316392

RESUMEN

INTRODUCTION: The number of young women who wish to become pregnant opting for kidney transplants is increasing, as becoming pregnant under hemodialysis or peritoneal dialysis is associated with many risks. However, there have been reports indicating that these patients are subject to a higher risk of miscarriage compared to women with normal renal function. We examine and report cases of patients that experienced pregnancy after undergoing kidney transplantation at our hospital. SUBJECTS AND METHOD: Of the kidney transplantation cases that were performed at our hospital between 1985 and 2016, there were 7 cases of pregnancy. The serum creatinine levels, urine protein findings, etc, of these 7 cases were examined during the pre-pregnancy, pregnancy, childbirth, and postpartum periods. RESULTS: All 7 cases were able to give birth. There were two cases of transient postpartum hypertension. There were no cases of obvious pregnancy toxemia or fetal growth retardation. Two of the cases resulted in the failure of the transplanted kidneys. DISCUSSION: According to previous studies on pregnancy and childbirth after kidney transplantation, the presence of high blood pressure and proteinuria as well as the renal function at the time of pregnancy is closely associated with postpartum renal function. Urine protein was detected prior to pregnancy in both cases and resulted in the failure of the transplanted kidneys. The influence of immunosuppressants on the mother and fetus is also an important consideration. CONCLUSION: We believe it is extremely important to ensure a thorough informed consent process prior to pregnancy and systematic use of immunosuppressants for young female transplant recipients.


Asunto(s)
Trasplante de Riñón , Complicaciones del Embarazo/epidemiología , Complicaciones del Embarazo/etiología , Resultado del Embarazo , Embarazo/estadística & datos numéricos , Adulto , Femenino , Humanos , Inmunosupresores/uso terapéutico , Factores de Riesgo , Adulto Joven
20.
Transplant Proc ; 50(8): 2457-2460, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30316378

RESUMEN

BACKGROUND: Extended-release tacrolimus (TacER), administered once daily, offers improved adherence with reduced side effects while still maintaining an immunosuppressive potency equivalent to that of conventional tacrolimus preparations. METHODS: The study included 83 patients who received consecutive living-donor kidney transplants at our facility from June 2013 to December 2016. Comparisons were made between 48 cases of induction with TacER and 35 cases of induction with cyclosporine (CyA). The observation period was 3 months after transplantation. Transplanted kidney function, rejection, infectious disease, lipid abnormalities, and glucose tolerance were compared. RESULTS: The 2 groups showed no significant difference in donor background or transplanted kidney function. Within the 3-month observation period, an acute rejection response was observed in 2 cases in the TacER group and in 8 cases in the CyA group. After transplantation, hyperlipidemia requiring medication was observed more frequently in the CyA group. The 2 groups did not show a marked difference in systemic infection or renal calcineurin inhibitor toxicity in histopathologic examination of the transplanted kidneys 3 months after surgery. DISCUSSION: Proactive use of TacER leads to improved adherence while yielding immunosuppressive potency equivalent to that of conventional tacrolimus preparations; however, tacrolimus has a potent blood sugar-elevating effect; thus, direct comparison with the CyA group is important for assessing the side effects. CONCLUSION: TacER has the potential to also reduce side effects in the early stages after surgery, suggesting its potential as a drug of first choice.


Asunto(s)
Ciclosporina/uso terapéutico , Rechazo de Injerto/prevención & control , Inmunosupresores/uso terapéutico , Trasplante de Riñón , Tacrolimus/administración & dosificación , Adulto , Preparaciones de Acción Retardada , Femenino , Rechazo de Injerto/epidemiología , Humanos , Donadores Vivos , Masculino , Persona de Mediana Edad , Adulto Joven
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