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1.
Oral Oncol ; 116: 105245, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33901866

RESUMO

BACKGROUND: The prognostic value of pretreatment complete blood count (CBC) data, including absolute lymphocyte count (ALC) and the neutrophil-to-lymphocyte ratio (NLR), has been reported for many diseases with decreased ALC and increased absolute neutrophil count (ANC) and NLR values correlating with worse outcomes. There is minimal data relating these hematologic parameters to oropharyngeal squamous cell carcinoma (OPSCC) prognosis. This study evaluates the prognostic value of pretreatment CBC data in OPSCC on overall survival (OS) and progression-free survival (PFS) in relation to HPV status. METHODS: A single-institutional retrospective review of patients with pretreatment hematologic data who received radiation for OPSCC was performed. Univariate and multivariate (UVA/MVA) Cox proportional hazard regression analyses were performed to identify prognostic variables. Translational studies related outcomes to the degree of tumor-infiltrating lymphocytes (TILs) in histologic specimens. RESULTS: From 2007 to 2018, 201 patients were treated for OPSCC. Median follow-up was 40 months. 3-year OS was 86.2% in the HPV-positive cohort, 46.3% for HPV-negative. Median NLR was 3.04. NLR ≥ 3 was associated with worse PFS (HR 1.67, p = 0.044. In the subset of 158 HPV + patients, MVA revealed increasing ALC to be associated with improved OS (HR 0.53; p = 0.040) and PFS (HR = 0.48; p = 0.0075). On UVA, high-TIL infiltration at diagnosis was associated with improved OS. CONCLUSION: In a cohort of HPV + OPSCC patients, increasing ALC is associated with improved OS and PFS. Our study is the first to identify pre-treatment ALC as an independent prognostic factor in HPV-associated OPSCC.


Assuntos
Neoplasias Orofaríngeas , Infecções por Papillomavirus , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Contagem de Linfócitos , Neoplasias Orofaríngeas/sangue , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/virologia , Papillomaviridae , Infecções por Papillomavirus/sangue , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Prognóstico , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/sangue , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia
2.
Transplant Proc ; 51(5): 1511-1515, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31155184

RESUMO

BACKGROUND: The autonomic innervation to a liver graft remains lost up to 1 year after liver transplant. Therefore, we investigated the effects of recipients' autonomic nervous activity on the extent of portal hyperperfusion of a partial liver graft in the absence of the autonomic innervation. METHODS: A total of 31 cirrhotic recipients undergoing right lobe living donor liver transplant were analyzed. Following a 10-minute absence of surgical stimulation after hepatic artery and bile duct reconstruction, the electrocardiogram and blood pressure waveforms were recorded for 5 minutes. Low-frequency (LF) and high-frequency (HF) powers and their ratio (LF/HF) were calculated using fast Fourier transform from the electrocardiogram waveform. A decrease in LF/HF represents a shift in sympathovagal balance toward parasympathetic predominance. Then, portal venous (PVF) and hepatic arterial (HAF) blood flows were measured in mL/min per 100 g of liver weight using spectral Doppler ultrasonography. A decrease in their ratio (PVF/HAF) represents attenuation of portal hyperperfusion. RESULTS: The medians of the PVF and HAF were 349 and 27 mL/min/100 g liver weight with interquartile ranges of 272 to 617 mL/min/100 g liver weight and 22 to 41 mL/min/100 g liver weight, respectively, yielding a median of the PVF/HAF of 13.7 (interquartile range, 8.5-21.3). The median of LF/HF was 0.67 (interquartile range, 0.16-1.45). With a reduction in LF/HF, PVF/HAF decreased according to an S-curve regression model between them (PVF/HAF=e2.743+-0.031LF/HF,adjustedR2=0.129,P=0.027). CONCLUSION: A shift in sympathovagal balance toward parasympathetic predominance is associated with attenuation of portal hyperperfusion in a partial liver graft.


Assuntos
Hemodinâmica/fisiologia , Circulação Hepática , Cirrose Hepática/cirurgia , Transplante de Fígado , Sistema Nervoso Parassimpático/fisiologia , Feminino , Humanos , Circulação Hepática/fisiologia , Doadores Vivos , Masculino
3.
Transplant Proc ; 50(9): 2664-2667, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30401373

RESUMO

Double portal vein (PV) branches during living donor liver transplantation (LDLT) with right lobe grafts have been considered challenging both in terms of donor safety and the complexity of vascular reconstruction in the recipient. Herein, we describe our experience with 24 adult LDLT recipients during which we employed unification patch venoplasty to reconstruct right lobe grafts with double PV orifices. We retrospectively reviewed the outcomes of 195 adult LDLT recipients receiving right lobe grafts, including 24 cases of adult LDLT recipients in which unification patch venoplasty was used to treat double PVs from January 2010 to June 2015. The anomalous portal vein branches of the donors were of type II in 7 cases (29.2%), type III in 15 cases (62.5%), and type IV in 2 cases (8.3%). We used propensity score matching analysis to compare the clinical outcomes of these recipients with those of 59 recipients who underwent adult LDLT using right lobe grafts with normal PVs in the same period. Intraoperative PV stenting was necessary in 2 (8.3%) of the 24 recipients undergoing unification patch venoplasty. During the follow-up period, all PVs remained patent until death or censoring. No significant difference in terms of postoperative vascular complications was evident between the 2 groups. Moreover, no major complications requiring reoperation or endoscopic and/or radiologic intervention developed in any of the 24 living donors with double PVs. In conclusion, our simplified unification patch venoplasty could be safe and feasible when used to reconstruct double PV orifices in right lobe LDLT from donors with complex PV anomalies.


Assuntos
Transplante de Fígado/métodos , Procedimentos de Cirurgia Plástica/métodos , Veia Porta/anormalidades , Veia Porta/cirurgia , Malformações Vasculares/cirurgia , Adulto , Feminino , Hepatectomia/métodos , Humanos , Fígado/irrigação sanguínea , Fígado/cirurgia , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Retrospectivos , Coleta de Tecidos e Órgãos/métodos , Transplantes/irrigação sanguínea , Transplantes/cirurgia , Resultado do Tratamento
4.
Transplant Proc ; 48(4): 1134-8, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27320573

RESUMO

The outcomes of patients who undergo ABO-incompatible (ABO-I) living-donor liver transplantation (LDLT) have markedly improved as strategies have become more innovative and advanced. Here, we describe 25 cases of ABO-I LDLT with a simplified protocol and compare the outcomes to those of ABO-compatible LDLT. We analyzed outcomes via a retrospective review of 182 adult LDLT cases including 25 ABO-I LDLTs from January 2011 to December 2014. Propensity scoring was used to compare the groups. The desensitization protocol included plasma exchange, rituximab, and intravenous immunoglobulin without local infusion therapy. The triple immunosuppression protocol consisted of tacrolimus and steroids with mycophenolate mofetil; a splenectomy was not routinely performed. The median age of recipients was 51 years (range, 35-66 years), and the median mean Model for End-Stage Liver Disease (MELD) score was 15 (range, 7-37). The initial ranges of isoagglutinin IgM and IgG titers were 1:1 to 1:256 and 1:4 to 1:2048, respectively. There were no significant differences in patient demographics or perioperative variables between the groups. Although significant rebound elevation in anti-ABO antibody during the postoperative period was observed in 3 cases, neither C4d staining nor clinical signs of antibody-mediated rejection was apparent in these cases. No diffuse intrahepatic biliary stricture was encountered in any ABO-I LDLT patient within a mean follow-up of 22.6 ± 17.2 months. Moreover, no significant difference in overall or graft survival was observed between the groups. ABO-I LDLT can be performed safely under this new simplified protocol and may be proposed when ABO-compatible donors are unavailable.


Assuntos
Incompatibilidade de Grupos Sanguíneos/tratamento farmacológico , Dessensibilização Imunológica/métodos , Rejeição de Enxerto/prevenção & controle , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Imunossupressores/uso terapêutico , Transplante de Fígado/métodos , Rituximab/uso terapêutico , Corticosteroides/uso terapêutico , Adulto , Idoso , Incompatibilidade de Grupos Sanguíneos/imunologia , Feminino , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto , Humanos , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/uso terapêutico , Troca Plasmática/métodos , Pontuação de Propensão , Estudos Retrospectivos , Tacrolimo/uso terapêutico
5.
Transplant Proc ; 48(4): 1190-3, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27320584

RESUMO

BACKGROUND: Impaired renal function is a strong risk factor for morbidity and mortality after liver transplantation (LT). There is clearly a progressive deterioration in renal function after LT. The greatest loss of renal function occurs within the 1st year after LT. Several factors, including calcineurin inhibitors, are associated with decreased renal function. The aims of the present study were to identify changes in renal function before and after LT and to determine the risk factors related to decreased renal function after LT. METHODS: We reviewed medical records of 106 LT recipients without moderate to severe chronic kidney disease (estimated glomerular filtration rate [eGFR] ≥60 mL/min/1.73 m(2)). We investigated eGFR changes from before to 1 year after LT with the use of propensity score matching. Statistical significance of differences between clinical parameters and 1-year eGFR changes was assessed with the use of univariate and multivariate analyses. RESULTS: Mean age was 49.5 ± 10.9 years, and 66% of the patients were male. Mean differences in 1-year eGFR and serum creatinine were -32.0 ± 29.2 mL/min/1.73 m(2) and 0.3 ± 0.3 mg/dL, respectively. Variables significantly associated with renal dysfunction 1 year after LT were old age, low pre-LT eGFR, low post-LT hemoglobin, and perioperative acute kidney injury. Multivariate analysis showed that pre-LT renal function was an independent risk factor for decreased renal function after LT. However, there was no significant correlation between 1-year eGFR change and serum tacrolimus level. CONCLUSIONS: Renal function significantly decreased the 1st year after LT, and baseline renal function was an independent risk factor for worsening renal function in LT recipients.


Assuntos
Inibidores de Calcineurina/uso terapêutico , Diabetes Mellitus/epidemiologia , Taxa de Filtração Glomerular , Rejeição de Enxerto/prevenção & controle , Hepatite C/epidemiologia , Hipertensão/epidemiologia , Hepatopatias/cirurgia , Transplante de Fígado , Complicações Pós-Operatórias/epidemiologia , Proteinúria/epidemiologia , Insuficiência Renal Crônica/epidemiologia , Adulto , Fatores Etários , Feminino , Seguimentos , Humanos , Testes de Função Renal , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais
6.
Transplant Proc ; 48(4): 1208-11, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27320588

RESUMO

Cytomegalovirus (CMV) infection in patients with liver transplantation (LT) remains a highly prevalent complication with a significant increase in morbidity and mortality. However, CMV-associated meningoencephalitis is rarely diagnosed, and treatment is very difficult. The aim of the present report is to review the experience of successful treatment with combined ganciclovir and foscarnet of CMV-associated meningoencephalitis refractory to ganciclovir alone in a hemodialysis (HD) patient after LT. A 54-year-old woman with end-stage renal disease on HD developed a seizure with loss of consciousness. She had received a liver transplant 4 months before. Blood CMV polymerase chain reaction was positive, and cerebrospinal fluid (CSF) analysis was compatible with viral meningitis. Brain magnetic resonance imaging (MRI) showed extensive dural thickening with enhancement and a round ring-like enhancement in the left centrum semiovale. She was diagnosed with CMV-associated meningoencephalitis. At that time, ganciclovir was started intravenously. After that, there were no improvements in mental state, CSF analysis, or brain MRI. Intravenous foscarnet at reduced dose was added to ganciclovir therapy. With combined ganciclovir and foscarnet, there was a slight improvement in her mental state and brain MRI.


Assuntos
Antivirais/uso terapêutico , Infecções por Citomegalovirus/tratamento farmacológico , Foscarnet/uso terapêutico , Ganciclovir/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Imunossupressores/efeitos adversos , Falência Renal Crônica/terapia , Transplante de Fígado , Meningoencefalite/tratamento farmacológico , Diálise Renal , Citomegalovirus/genética , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/etiologia , Quimioterapia Combinada , Feminino , Humanos , Falência Renal Crônica/complicações , Meningoencefalite/diagnóstico , Meningoencefalite/etiologia , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase
7.
Transplant Proc ; 47(4): 1194-8, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-26036552

RESUMO

BACKGROUND: The association between intraoperative systemic hemodynamic status and preventing portal hyperperfusion, which induces shear stress on the sinusoidal endothelial cells of liver grafts, resulting in poor graft function in live-donor recipients, has not been identified. This study evaluates the effects of systemic hemodynamic parameters (SHPs) during the neohepatic phase on changes in hepatic hemodynamic parameters (HHPs) between the neohepatic phase and the 1st postoperative day. METHODS: Thirty-eight patients undergoing living donor liver transplantation (LDLT) were enrolled in this study. HHPs (flow velocities of portal vein and hepatic artery) were measured immediately after hepatic artery and bile duct reconstruction and on the first postoperative day. SHPs (mean arterial pressure, central venous pressure [CVP], cardiac index, stroke volume variation, stroke volume index, systemic vascular resistance index, and central venous oxygen saturation) were recorded and averaged for 5 minutes after the measurement of HHPs. The relationships between the SHPs and HHPs were assessed using linear or quadratic regression analysis. RESULTS: Peak portal vein flow velocity (PVV) decreased on the 1st postoperative day in 24 patients (63%). There was an inverted-U relationship between CVP and the percentage change in PVV (R(2) = 0.241, P = .008). According to the quadratic regression model, the PVV maximally decreased at a CVP of 7.8 mm Hg. No significant correlations were found between the other SHPs and HHPs. CONCLUSIONS: Maintaining CVP (approximately 8 mm Hg) during the neohepatic phase was clinically beneficial in decreasing PVV to prevent portal hyperperfusion in the early postoperative period of LDLT.


Assuntos
Pressão Venosa Central/fisiologia , Artéria Hepática/fisiologia , Transplante de Fígado/métodos , Veia Porta/fisiologia , Complicações Pós-Operatórias/prevenção & controle , Lesões do Sistema Vascular/prevenção & controle , Adulto , Velocidade do Fluxo Sanguíneo/fisiologia , Estudos de Coortes , Feminino , Hemodinâmica , Hepatectomia , Humanos , Fígado/cirurgia , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Prospectivos , Circulação Esplâncnica , Estresse Mecânico
8.
Transplant Proc ; 47(3): 694-9, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25891713

RESUMO

BACKGROUND: Although a temporary portocaval shunt (TPCS) improves hemodynamic stability during liver transplantation, the role of TPCS is controversial. We assessed the effects of TPCS in patients undergoing living-donor liver transplantation (LDLT) with a difficult total hepatectomy. METHODS: We analyzed outcomes by means of retrospective review of 116 LDLTs performed in our institution from May 2011 to October 2013; among these, 33 recipients received TPCS (group I) and 83 did not (group II). We performed TPCS in a high-risk group, such as those with severe perihepatic adhesions, severe retrohepatic adhesions to the vena cava, or massive bleeding during total hepatectomy. Patient demographics and intraoperative and postoperative variables were reviewed. RESULTS: No significant differences were observed in the perioperative variables except intraoperative blood loss. The transfusion requirement and operative time in group I were similar to those in group II despite the higher blood loss and more complicated cases. Hemodynamic status and the vasopressor requirement during the operation were similar between the 2 groups. We also compared 2 subgroups to evaluate the effects of TPCS more precisely in the high-risk patients: subgroup A (Model for End-Stage Liver Disease score [MELD], >20) and subgroup B (MELD, ≤20). The intraoperative requirements for platelet concentrate and epinephrine during the early reperfusion phase in subgroup A were significantly lower than those in subgroup A without TPCS. CONCLUSIONS: TPCS was a safe and useful procedure to improve hemodynamic status and postoperative LDLT outcomes in high-risk and select patients.


Assuntos
Hepatectomia/métodos , Transplante de Fígado/métodos , Doadores Vivos , Derivação Portocava Cirúrgica/métodos , Adulto , Idoso , Perda Sanguínea Cirúrgica , Transfusão de Sangue/estatística & dados numéricos , Doença Hepática Terminal/cirurgia , Feminino , Hemodinâmica , Hepatectomia/efeitos adversos , Humanos , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Estudos Retrospectivos , Resultado do Tratamento
9.
Transplant Proc ; 46(3): 754-7, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24767341

RESUMO

Since various innovative strategies including local infusion therapy and rituximab have been introduced, the survivals and outcomes of recipients in ABO-incompatible (ABO-I) living donor liver transplantation (LDLT) have remarkably improved. Thus, ABO-I LDLT can be a feasible therapeutic option for the patient with end-stage liver disease if an ABO-compatible donor is not available. Although most ABO-I protocols are based on rituximab, plasma exchange, and local infusion therapy, treatment strategies have been changing according to a center's preference or their results. Nonetheless, the consensus of the ABO-I LDLT protocol remains undetermined. Herein, we present our experience with new simple ABO-I LDLT protocol and the excellent results for 14 patients from January 2011 to May 2013. All patients were administrated a single dose of rituximab over 7 days before transplantation followed by plasma exchange to lower anti-ABO antibody titer ≤32. The basic immunosuppression protocol consisted of tacrolimus and steroids with mycophenolate mofetil starting 3 days before transplantation. Splenectomy was not performed routinely and local infusion therapy was not applied at the postoperative period. Instead, the patients received intravenous immunoglobulin (IVIG) after LDLT on days 1, 3, and 5. Neither antibody-mediated rejection nor biliary stricture were encountered in the patients, with a mean follow-up of 16.27 ± 9.4 months. This new simplified ABO-I LDLT protocol seems to prevent antibody-mediated rejection and could be considered as the safe and effective modality to overcome the ABO blood-type barrier in LDLT.


Assuntos
Sistema ABO de Grupos Sanguíneos , Imunoglobulinas Intravenosas/administração & dosagem , Transplante de Fígado , Doadores Vivos , Adulto , Feminino , Humanos , Imunossupressores/administração & dosagem , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Taxa de Sobrevida
10.
Horm Behav ; 62(5): 598-604, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22982020

RESUMO

Ghrelin is an orexigenic hormone that regulates homeostatic and reward-related feeding behavior. Recent evidence indicates that acylation of ghrelin by the gut enzyme ghrelin O-acyl transferase (GOAT) is necessary to render ghrelin maximally active within its target tissues. Here we tested the hypothesis that GOAT activity modulates food motivation and food hedonics using behavioral pharmacology and mutant mice deficient for GOAT and the ghrelin receptor (GHSR). We evaluated operant responding following pharmacological administration of acyl-ghrelin and assessed the necessity of endogenous GOAT activity for operant responding in GOAT and GHSR-null mice. Hedonic-based feeding behavior also was examined in GOAT-KO and GHSR-null mice using a "Dessert Effect" protocol in which the intake of a palatable high fat diet "dessert" was assessed in calorically-sated mice. Pharmacological administration of acyl-ghrelin augmented operant responding; notably, this effect was dependent on intact GHSR signaling. GOAT-KO mice displayed attenuated operant responding and decreased hedonic feeding relative to controls. These behavioral results correlated with decreased expression of the orexin-1 receptor in reward-related brain regions in GOAT-KO mice. In summary, the ability of ghrelin to stimulate food motivation is dependent on intact GHSR signaling and modified by endogenous GOAT activity. Furthermore, GOAT activity is required for hedonic feeding behavior, an effect potentially mediated by forebrain orexin signaling. These data highlight the significance of the GOAT-ghrelin system for the mediation of food motivation and hedonic feeding.


Assuntos
Aciltransferases/fisiologia , Comportamento Alimentar/fisiologia , Grelina/metabolismo , Acilação/fisiologia , Aciltransferases/genética , Aciltransferases/metabolismo , Animais , Regulação do Apetite/efeitos dos fármacos , Regulação do Apetite/genética , Regulação do Apetite/fisiologia , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Peso Corporal/fisiologia , Comportamento Alimentar/efeitos dos fármacos , Grelina/sangue , Grelina/farmacologia , Grelina/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular/sangue , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Masculino , Proteínas de Membrana , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Motivação/efeitos dos fármacos , Motivação/genética , Motivação/fisiologia , Neuropeptídeos/sangue , Neuropeptídeos/metabolismo , Orexinas
11.
Transplant Proc ; 44(2): 466-8, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22410046

RESUMO

INTRODUCTION: Biliary reconstruction remains the "Achilles' heel" of living donor liver transplantation (LDLT). In the last decades, the technical aspects of biliary reconstruction have been debated for their impact on biliary complications in LDLT. A microsurgical technique in biliary reconstruction is more attractive. PATIENTS AND METHODS: From December 2010 to June 2011, 15 primary LDLTs underwent duct-to-duct biliary reconstruction using a microscopic technique. External stents were inserted in all patients. All procedures were performed under a microscope by a single transplant microsurgeon. RESULTS: The time consumed for bile duct reconstruction using the microscopic technique was 35 minutes. There were 8 grafts with a single bile duct orifice and seven with two orifices. The average duct size was 3 mm in patients with two orifices and 5 mm in those with a single orifice. There was no bile leak or biliary stricture associated with the biliary reconstruction over a median 5-month follow-up. There were two cases of bile leakage from the cut hepatic surface. CONCLUSION: The microscopic technique reduced early biliary complications. However, further technical advances are needed to decrease the time consumptions for the procedure.


Assuntos
Ductos Biliares/cirurgia , Procedimentos Cirúrgicos do Sistema Biliar , Transplante de Fígado/métodos , Doadores Vivos , Microcirurgia , Procedimentos de Cirurgia Plástica , Adulto , Anastomose Cirúrgica , Doenças dos Ductos Biliares/etiologia , Procedimentos Cirúrgicos do Sistema Biliar/efeitos adversos , Procedimentos Cirúrgicos do Sistema Biliar/instrumentação , Estudos de Viabilidade , Feminino , Humanos , Transplante de Fígado/efeitos adversos , Transplante de Fígado/instrumentação , Masculino , Microcirurgia/efeitos adversos , Microcirurgia/instrumentação , Pessoa de Meia-Idade , Procedimentos de Cirurgia Plástica/efeitos adversos , Procedimentos de Cirurgia Plástica/instrumentação , República da Coreia , Stents , Fatores de Tempo , Resultado do Tratamento
12.
Neuroscience ; 210: 243-8, 2012 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-22433299

RESUMO

Data from our laboratory indicate that the orexin system is involved in the regulation of both conditioned and unconditioned responding for palatable foods. Anticipation of food rewards activates orexin receptor containing neurons within the paraventricular nucleus of the thalamus (PVT). The PVT regulates mesolimbic dopamine neurochemistry through direct connections with the nucleus accumbens and modulates the processing of cognitive-emotional information, suggesting that the PVT may represent a unique brain region with the capacity to mediate orexinergic effects on brain dopamine and behavior. Here, we tested the hypothesis that PVT orexin signaling mediates mesolimbic dopamine and reward-based feeding. To do this we used a behavioral pharmacological approach in tandem with central genetic manipulation of the orexin-1 receptor in the PVT. Data from these studies indicate that orexin-A action in the PVT increases dopamine levels in the nucleus accumbens. In addition, endogenous orexin signaling in the PVT mediates locomotor activity and hedonic feeding responses. Together these data highlight the PVT as a critical site capable of mediating orexin action on brain dopamine and reward-based feeding.


Assuntos
Dopamina/metabolismo , Comportamento Alimentar/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neuropeptídeos/metabolismo , Núcleo Hipotalâmico Paraventricular/metabolismo , Transdução de Sinais/fisiologia , Animais , Imuno-Histoquímica , Masculino , Atividade Motora/fisiologia , Orexinas , RNA Interferente Pequeno , Ratos , Ratos Long-Evans , Reação em Cadeia da Polimerase em Tempo Real
13.
Neuroscience ; 167(1): 11-20, 2010 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-20149847

RESUMO

Consumption beyond homeostatic needs, referred to here as reward-based feeding behavior, is a central contributor to the current obesity epidemic worldwide. Importantly, reward-based feeding can be driven by palatability, the taste and texture of the food, as well as cues associated with the consumption of palatable foods. The hypothalamic orexin system regulates both diet preference and anticipation of food rewards making it a likely target to modulate reward-based feeding behavior. In the current manuscript we hypothesized that orexin signaling mediates food-motivated behaviors and reward-based feeding behavior. We further hypothesized that orexin neurons and targets of the orexin system become activated in response to cues associated with the consumption of palatable food. Data from these studies suggest that orexin signaling promotes progressive ratio responding for palatable foods while blockade of orexin signaling attenuates reward-based feeding of a high fat diet. In addition, cues linked to the consumption of chocolate, or the receipt of a daily meal, activate the orexin system and its target regions differentially. Collectively, these data suggest that orexin signaling mediates reward-based feeding behavior and, within specific target regions, may regulate cue-induced overconsumption of palatable foods.


Assuntos
Comportamento Alimentar/fisiologia , Alimentos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Motivação/fisiologia , Neurônios/fisiologia , Neuropeptídeos/metabolismo , Recompensa , Animais , Benzoxazóis/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/fisiologia , Cacau , Fármacos do Sistema Nervoso Central/farmacologia , Sinais (Psicologia) , Gorduras na Dieta , Ingestão de Alimentos/efeitos dos fármacos , Ingestão de Alimentos/fisiologia , Comportamento Alimentar/efeitos dos fármacos , Masculino , Motivação/efeitos dos fármacos , Naftiridinas , Neurônios/efeitos dos fármacos , Receptores de Orexina , Orexinas , Ratos , Ratos Long-Evans , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Neuropeptídeos/antagonistas & inibidores , Receptores de Neuropeptídeos/metabolismo , Ureia/análogos & derivados , Ureia/farmacologia
14.
Transplant Proc ; 40(8): 2835-6, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18929876

RESUMO

Diffuse-type hepatocellular carcinoma (HCC) is a contraindication to liver transplantation (OLT). However, cirrhotomimetic HCC, which is a form of the diffuse type, is difficult to diagnose preoperatively, there are no published reports about its prognosis after OLT. We performed an OLT for a case of cirrhotomimetic HCC diagnosed postoperatively. This 41-years-old man was on the waiting list for OLT owing to hepatitis B virus-related liver cirrhosis and esophageal variceal bleeding. Three months before transplantation, newly developed small nodules were detected on computed tomography (CT); there were no interval changes on CT after 2 months. His serum value of alpha-fetoprotein (alpha-FP) was 327 ng/mL. The patient received a deceased donor liver transplantation and his postoperative course was uneventful. However, on pathologic findings, the explanted liver showed malignant cells in most cirrhotic nodules. So, the patient's pathologic diagnosis was cirrhotomimetic HCC. Triple immunosuppression was administered and steroid stopped at about 2 weeks after transplantation. Eighteen months after transplantation, alpha-FP was 1.5 ng/mL and there was no evidence of recurrence on follow-up CT. In conclusion, cirrhotomimetic HCC is rare and difficult to detect, preoperatively. Despite the short-term follow-up, we did not detect recurrence of HCC.


Assuntos
Carcinoma Hepatocelular/patologia , Hepatite B/cirurgia , Cirrose Hepática/cirurgia , Neoplasias Hepáticas/patologia , Transplante de Fígado/patologia , Complicações Pós-Operatórias/patologia , Adulto , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Doxorrubicina/uso terapêutico , Seguimentos , Humanos , Imunossupressores/uso terapêutico , Cirrose Hepática/etiologia , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Resultado do Tratamento
15.
Acta Radiol ; 45(1): 18-22, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15164774

RESUMO

Metaplastic carcinoma of the breast is a rare disease. We describe the MRI findings with the correlative sonographic and pathologic features of two cases. On MRI, T2-weighted images demonstrate a relatively well-defined mass with high signal intensity cystic components. Dynamic enhancement subtraction images showed an early enhancing and delayed washout peripheral rim and non-enhancing internal components. A microlobulated, isoechogenic mass with cystic components was seen sonographically, and was histopathology related to necrosis and cystic degeneration. Although these features are not unique, metaplastic carcinoma should be included in the differential diagnosis for breast masses.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Carcinoma/diagnóstico por imagem , Carcinoma/patologia , Imageamento por Ressonância Magnética , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Ultrassonografia
16.
Br J Radiol ; 77(916): 344-6, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15107329

RESUMO

Sclerosing peritonitis (SP) is a rare but serious complication of chronic ambulatory peritoneal dialysis (CAPD). SP is characterized by thickening of the peritoneum that encloses some or all of the small intestine. However, the early clinical features of SP are non-specific and are often not recognized until the patient develops complications. The most common complications of SP appear to be partial or complete small bowel obstruction, small bowel necrosis, and enterocutaneous fistulae, all of which, necessitate surgical intervention and have high mortality rates. Although the CT findings of SP are well recognized, to our knowledge, large bowel obstruction due to SP without peritoneal change have not been reported. We report a case of large bowel obstruction due to peritoneal sclerosis following long-term CAPD.


Assuntos
Colo Ascendente/patologia , Doenças do Colo/etiologia , Obstrução Intestinal/etiologia , Peritonite/complicações , Doenças do Colo/diagnóstico por imagem , Doenças do Colo/patologia , Feminino , Humanos , Obstrução Intestinal/diagnóstico por imagem , Obstrução Intestinal/patologia , Pessoa de Meia-Idade , Peritonite/diagnóstico por imagem , Peritonite/patologia , Radiografia , Esclerose
17.
Acta Radiol ; 44(2): 166-71, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12694103

RESUMO

PURPOSE: Coded harmonic angio (CHA) US is a recently developed technique that can depict the effects of contrast agents. The purpose of this study was to determine the role of this technique in depicting the enhancement patterns of various renal perfusion abnormalities compared with dynamic CT. MATERIAL AND METHODS: During a 6-month period, various renal lesions including renal cell carcinoma (n=12), transitional cell carcinoma (n=5), acute pyelonephritis (n=5), and renal trauma (n=2) were evaluated with CHA US using a microbubble contrast agent. US images were obtained before contrast administration and with a bolus injection of 4 g of microbubble contrast agent (300 mg/ml) every 10 s for 1 min and every minute for 5 min. The contrast enhancement patterns of various renal masses were compared with dynamic CT. RESULTS: Of 12 renal cell carcinomas, 9 (75%) showed heterogeneous enhancement and the remaining 3 (25%) showed homogeneous enhancement. Enhancement of more than adjacent renal parenchyma was seen 16-252 s after injection. The duration of enhancement was 13-208 s (mean, 80 s). All transitional cell carcinomas showed peripheral enhancement. Enhancement was seen 22-270 s after injection. The duration of enhancement was 191-238 s (mean, 291 s). Five patients with acute pyelonephritis and 2 with renal trauma showed focal perfusion defects not shown on the pre-contrast examinations. CONCLUSION: CHA US with microbubble contrast agent is an effective US technique for the evaluation of both tumor vascularity and renal perfusion abnormality.


Assuntos
Meios de Contraste , Nefropatias/diagnóstico por imagem , Neoplasias Renais/diagnóstico por imagem , Adulto , Idoso , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células de Transição/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Perfusão , Ultrassonografia
18.
Asian J Surg ; 25(4): 277-84, 2002 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-12470999

RESUMO

Between February 1997 and December 2001, 311 adult-to-adult living donor liver transplants (A-A LDLTs) were performed at the Asan Medical Center for patients above 20 years of age. Indications for A-A LDLT were: chronic hepatitis B (203), chronic hepatitis C (5), hepatocellular carcinoma (64), alcoholic cirrhosis (9), cryptogenic cirrhosis (4), secondary biliary cirrhosis (5), primary biliary cirrhosis (1), Wilson' s disease (2), autoimmune hepatitis (1), hepatic tuberculosis (1), cholangiocarcinoma (1), fulminant hepatic failure (14) and primary non-function of cadaveric liver graft (1). Of 311 A-A LDLTs, 36 were of medical high urgency, 20 were for acute and subacute hepatic failure, 15 were for hepato-renal syndrome and 1 was for primary non-function. Recipient age ranged from 27 to 64 years. Donor age ranged from 16 to 62 years. There was no donor mortality. Implanted liver grafts were categorized into seven types: 175 modified right lobe (MRL), 70 left lobe, 32 right lobe, 20 dual grafts, 10 left lobe plus caudate lobe, three extended right lobe and one posterior segment. In MRL, the tributaries of the middle hepatic vein were reconstructed by interpositioning a vein graft. Indication for dual graft implantation was the same as single graft A-A LDLT, and four of 20 were emergency cases. Of 20 dual grafts, 14 received two left lobes, four received a left lobe and a lateral segment, one received a right lobe and a left lobe and one received a lateral segment and a posterior segment. Graft volume ranged from 28% to 83% of the standard liver volume of the recipients. There were 33 (10.6%) in-hospital mortalities (< 4 months) among the 310 patients after 311 A-A LDLTs. Of the 36 patients receiving emergency transplants, 31 survived. These encouraging results justify the expansion of A-A LDLT in coping with increasing demands, even in urgent situations. We have aimed to introduce the establishment of the efficacy of A-A LDLT in various end-stage chronic and acute liver diseases, as well as new technical advances to overcome small graft-size syndrome by using dual-graft implantation and MRL, both of which were first developed in our department.


Assuntos
Hepatopatias/cirurgia , Transplante de Fígado , Doadores Vivos , Adulto , Cadáver , Mortalidade Hospitalar , Humanos , Coreia (Geográfico)/epidemiologia , Transplante de Fígado/métodos , Transplante de Fígado/estatística & dados numéricos , Doadores Vivos/estatística & dados numéricos , Complicações Pós-Operatórias/mortalidade , Doadores de Tecidos
19.
Korean J Intern Med ; 12(1): 70-4, 1997 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9159042

RESUMO

A 58-year-old man described a short history of dyspnea and a preceding flu like illness with roentgenographic features of an interstitial lung disease. An open lung biopsy specimen from him showed bronchiolitis obliterans with organizing pneumonia (BOOP). Adenovirus was isolated from a throat swab. There was both clinical and radiographic improvement with supportive care. We herein report a first case of BOOP associated with adenovirus in Korea.


Assuntos
Infecções por Adenoviridae/diagnóstico , Infecções por Adenoviridae/virologia , Adenoviridae/isolamento & purificação , Pneumonia em Organização Criptogênica/diagnóstico , Pneumonia em Organização Criptogênica/virologia , Infecções por Adenoviridae/patologia , Biópsia , Lavagem Broncoalveolar , Pneumonia em Organização Criptogênica/patologia , Humanos , Coreia (Geográfico) , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Faringe/virologia , Testes de Função Respiratória , Tomografia Computadorizada por Raios X
20.
Korean J Intern Med ; 11(2): 113-21, 1996 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-8854647

RESUMO

OBJECTIVES: Interstitial lung diseases (ILD) are heterogeneous groups of disorders that involve the interstitium of the lung. Lung biopsy is mandatory in most cases of ILD for diagnosis. In Korea, a few clinical data about ILD were analyzed on the basis of pathologic proof. Thus, we analysed the clinical profiles of patients with ILD who had lung biopsy in a tertiary university hospital. METHODS: Clinical and pathologic data concerning 100 patients who had open lung biopsy (OLB) and/or transbronchial lung biopsy (TBLB) were prospectively analysed. Two patients were excluded because one patient was proven to have metastatic cancer and the other to have miliary tuberculosis. One patient had two combined diseases: rheumatoid arthritis and pneumoconiosis. Thus, 99 cases were analysed from 98 patients. Demographic characteristics, pulmonary functions and pathologic findings were analysed according to the disease entities of ILD. Pathologic findings were classified only in patients who had OLB. Clinical courses were also analysed during follow-up. RESULTS: OLB was performed on 68 cases with concomittant TBLB in 18 cases and 30 cases had TBLB only. Mediastinal lymph node biopsy has performed on one case. The most common cause of ILD was IPF (51.5%), which was followed by CVD.PF (15.2%) and HP (9.1%). Average age of 51 cases with idiopathic pulmonary fibrosis (IPF) was 60 +/- 11 years, that of 15 cases with collagen vascular disease associated pulmonary fibrosis (CVD-PF) was 46 +/- 17 years and that of 9 cases with hypersensitivity pneumonitis (HP) was 53 +/- 8.1 years. In IPF, CVD-PF AND HP, male to female ratio was equal. But female was dominant in sarcoidosis and male was dominant in pneumoconiosis. Pulmonary function tests (PFT) in IPF, CVD-PF and HP were restrictive patterns in half of the cases. In pneumoconiosis and sarcoidosis, PFT showed normal pattern. Usual interstitial pneumonia (UIP) was the most common pathologic type in IPF and CVD-PF. The most common cause of CVD-PF was rheumatoid arthritis. The overall mortality rate was 12.1%. CONCLUSION: We reported that the ILD had a variety of disease entities and pathologic types even in one tertiary referral hospital. We hope that a multi-center study will be performed on the basis of pathologic proof in the future.


Assuntos
Doenças Pulmonares Intersticiais/tratamento farmacológico , Adulto , Idoso , Biópsia , Feminino , Humanos , Pulmão/patologia , Pulmão/fisiopatologia , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/fisiopatologia , Masculino , Pessoa de Meia-Idade
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