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Pexastimogene devacirepvec (Pexa-Vec) is a vaccinia virus-based oncolytic immunotherapy designed to preferentially replicate in and destroy tumor cells while stimulating anti-tumor immunity by expressing GM-CSF. An earlier randomized Phase IIa trial in predominantly sorafenib-naïve hepatocellular carcinoma (HCC) demonstrated an overall survival (OS) benefit. This randomized, open-label Phase IIb trial investigated whether Pexa-Vec plus Best Supportive Care (BSC) improved OS over BSC alone in HCC patients who failed sorafenib therapy (TRAVERSE). 129 patients were randomly assigned 2:1 to Pexa-Vec plus BSC vs. BSC alone. Pexa-Vec was given as a single intravenous (IV) infusion followed by up to 5 IT injections. The primary endpoint was OS. Secondary endpoints included overall response rate (RR), time to progression (TTP) and safety. A high drop-out rate in the control arm (63%) confounded assessment of response-based endpoints. Median OS (ITT) for Pexa-Vec plus BSC vs. BSC alone was 4.2 and 4.4 months, respectively (HR, 1.19, 95% CI: 0.78-1.80; p = .428). There was no difference between the two treatment arms in RR or TTP. Pexa-Vec was generally well-tolerated. The most frequent Grade 3 included pyrexia (8%) and hypotension (8%). Induction of immune responses to vaccinia antigens and HCC associated antigens were observed. Despite a tolerable safety profile and induction of T cell responses, Pexa-Vec did not improve OS as second-line therapy after sorafenib failure. The true potential of oncolytic viruses may lie in the treatment of patients with earlier disease stages which should be addressed in future studies. ClinicalTrials.gov: NCT01387555.
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BACKGROUND: In new organ allocation policy, patients with hepatocellular carcinoma (HCC) experience a 6-month delay in being granted Model for End-Stage Liver Disease exception points. However, it may not be fair for patients at risk of early progression of HCC. METHODS: All patients who were diagnosed as United Network for Organ Sharing (UNOS) stage 1 or 2 of HCC between January 2004 and December 2012 were included. Patients who received surgical resection or liver transplant (LT) as a primary treatment and who did not receive any treatment for HCC were excluded. Patients with baseline Model for End-Stage Liver Disease score ≥22 were also excluded because they have a higher chance of receiving LT. Patients who developed extrahepatic progression within 1 year were considered as high-risk for early recurrence after LT. RESULTS: A total of 586 patients were included. Mean (SD) age was 59.9 (10.3) years and 409 patients (69.8%) were men. The cumulative incidence of estimated dropout was 8.9% at 6 months; size of the maximum nodule (≥3 cm) and nonachievement of complete response were independent factors. Extrahepatic progression developed in 16 patients (2.7%) within 1 year; size of the maximum nodule (4 cm) and alpha-fetoprotein level (>100 ng/mL) were independent predictors. CONCLUSIONS: The estimated dropout rate from the waiting list within 6 months was 8.9%. Advantage points might be needed for patients with maximum nodule size ≥3 cm or those with noncomplete response. However, in patients with maximum nodule size ≥4 cm or alpha-fetoprotein level >100 ng/mL, caution is needed.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Trasplante de Hígado , Selección de Paciente , Listas de Espera , Adulto , Anciano , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/cirugía , Progresión de la Enfermedad , Femenino , Humanos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Factores de Riesgo , Listas de Espera/mortalidadRESUMEN
Entecavir 0.5 mg (ETV) is widely used among treatment-naïve chronic hepatitis B (CHB) patients. However, 10%-30% of patients show partial virologic response (PVR) to the drug. If the hepatitis B virus (HBV) continues to replicate, the underlying liver disease may progress. Herein, we compared the efficacy of switching to tenofovir disoproxil fumarate (TDF) with that of continuing ETV in CHB patients with PVR to ETV. This was an open-label randomized controlled trial including CHB patients who had been receiving 0.5 mg of ETV for >12 months, but who still had detectable HBV DNA levels of >60 IU/mL without known resistance to ETV. Sixty patients were enrolled and 45 qualified for the study: Twenty-two patients were randomly assigned into the TDF group and 23 into the ETV group. After 12 months of treatment, the virologic response rate (HBV DNA <20 IU/mL) was significantly higher in the TDF group than in the ETV group, as measured using per-protocol analysis (55% vs 20%; P = .022) and intention-to-treat analysis (50% vs 17.4%; P = .020). The reduction in HBV DNA was greater (-1.13 vs -0.67 log10 IU/mL; P = .024), and the mean HBV DNA level was lower (1.54 vs 2.01 log10 IU/mL; P = .011) in the TDF group than in the ETV group. In conclusion, to achieve optimal response in CHB patients with PVR to ETV, switching to TDF would be a better strategy than continuing ETV. Appropriate modification of therapy would further improve the outcome of chronic HBV infection.
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Sustitución de Medicamentos , Guanina/análogos & derivados , Virus de la Hepatitis B/efectos de los fármacos , Hepatitis B Crónica/tratamiento farmacológico , Tenofovir/farmacología , Tenofovir/uso terapéutico , Adulto , Antivirales/farmacología , Antivirales/uso terapéutico , ADN Viral/sangre , Femenino , Guanina/farmacología , Guanina/uso terapéutico , Anticuerpos contra la Hepatitis B/sangre , Antígenos de la Hepatitis B/sangre , Virus de la Hepatitis B/inmunología , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Resultado del Tratamiento , Carga Viral/efectos de los fármacosRESUMEN
BACKGROUND: Preventing mother to child transmission of chronic hepatitis B infection in the setting of a high maternal viral load is challenging. The idea has emerged from antepartum tenofovir treatment with combination immunoprophylaxis. AIMS: To demonstrate the efficacy and safety of tenofovir to prevent mother to child transmission of hepatitis B virus. METHODS: PubMed, EMBASE, and Cochrane databases were searched through August 16, 2016. Comparative trials of second or third trimester tenofovir administration vs. controls for patients with chronic hepatitis B infection and non-comparative case series assessing mother to child transmission rates and evaluating maternal and foetal safety outcomes were included. RESULTS: Ten studies (one randomised controlled trial, four non-randomised controlled trials and five case series) that enrolled 733 women were included. The pooled results from comparative trials (599 pregnancies) showed that tenofovir significantly reduced the risk of infant hepatitis B surface antigen seropositivity by 77% (odds ratio=0.23, 95% confidence intervals=0.10-0.52, P=.0004) without heterogeneity (I2 =0%). In the case series analysis (134 pregnancies), only two cases (1.5%) of mother to child transmission with extremely high maternal viral load and non-compliance to treatment were identified. Maternal and foetal safety parameters including congenital malformation and foetal death were re-assuring. CONCLUSIONS: For pregnant women with high hepatitis B virus DNA levels, tenofovir administration in the second or third trimester can prevent mother to child transmission when combined with hepatitis B immunoglobulin and the hepatitis B vaccine. Tenofovir is safe and tolerable for both the mother and foetus.
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Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/transmisión , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Tenofovir/uso terapéutico , Terapia Combinada , Femenino , Vacunas contra Hepatitis B/uso terapéutico , Virus de la Hepatitis B/efectos de los fármacos , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/inmunología , Hepatitis B Crónica/epidemiología , Hepatitis B Crónica/terapia , Humanos , Lactante , Transmisión Vertical de Enfermedad Infecciosa/estadística & datos numéricos , Madres/estadística & datos numéricos , Embarazo , Complicaciones Infecciosas del Embarazo/epidemiología , Complicaciones Infecciosas del Embarazo/terapia , Tenofovir/efectos adversos , Resultado del Tratamiento , Carga Viral/efectos de los fármacos , Carga Viral/genéticaRESUMEN
In Korea, patients with chronic hepatitis C virus (HCV) infection are typically treated with pegylated interferon-alpha plus ribavirin, but interferons are contraindicated in many patients and are often poorly tolerated, particularly by the elderly and those with advanced liver disease. No interferon-free treatment regimens are approved in Korea. Sofosbuvir is an oral nucleotide analog inhibitor of the HCV nonstructural 5B RNA polymerase. It is approved in the USA, European Union and Japan for treating a number of HCV genotypes, including genotype 2. Genotype 2 has a seroprevalence of 38-46% in Korea. This single-arm, phase 3b study (NCT02021643) examined the efficacy and safety of sofosbuvir plus ribavirin (12-week duration) in chronic genotype 2 HCV-infected treatment-naive and treatment-experienced Korean patients with and without cirrhosis. The proportion of patients with sustained virologic response 12 weeks after treatment discontinuation (SVR12) was 97% (125/129), with 96% (101/105) of treatment-naive and 100% (24/24) of treatment-experienced patients achieving SVR12. Two patients experienced virologic failure (n = 1, on-treatment failure; n = 1, relapse). No patient discontinued study treatment due to an adverse event (AE). The most common treatment-emergent AEs were headache (18%, 23/129) and pruritus (15%, 19/129). Few patients had grade 3 AEs (5%, 6/129) or grade 3 laboratory abnormalities (12%, 15/129). No grade 4 AE was reported. These data suggest that 12 weeks of treatment with the all-oral, interferon-free regimen of sofosbuvir plus ribavirin is effective and well tolerated in Korean patients with chronic genotype 2 HCV infection.
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Antivirales/uso terapéutico , Genotipo , Hepacivirus/aislamiento & purificación , Hepatitis C Crónica/tratamiento farmacológico , Ribavirina/uso terapéutico , Sofosbuvir/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antivirales/efectos adversos , Pueblo Asiatico , Quimioterapia Combinada/efectos adversos , Quimioterapia Combinada/métodos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Femenino , Hepacivirus/clasificación , Hepacivirus/genética , Humanos , Masculino , Persona de Mediana Edad , Ribavirina/efectos adversos , Sofosbuvir/efectos adversos , Resultado del Tratamiento , Carga Viral , Adulto JovenRESUMEN
BACKGROUND: Dark circles refer to a symptom that present darkness under the eyes. Because of improvement in the quality of life, the dark circles have been recognized as one of major cosmetic concerns. However, it is not easy to classify the dark circles because they have various causes. METHODS: To select suitable instruments and detailed evaluation items, the dark circles were classified according to the causes through visual assessment, Wood's lamp test, and medical history survey for 100 subjects with dark circles. After the classification, were newly recruited for instrument conformity assessment. Through this, suitable instruments for dark circle evaluation were selected. We performed a randomized clinical trial for dark circles, a placebo-controlled double-blind study, using effective parameters of the instruments selected from the preliminary test. RESULTS: Dark circles of vascular type (35%) and mixed type (54%), a combination of pigmented and vascular types, were the most common. Twenty four subjects with the mixed type dark circles applied the test product (Vitamin C 3%, Vitamin A 0.1%, Vitamin E 0.5%) and placebo on randomized split-face for 8 weeks. The effective parameters (L*, a, M.I., E.I., quasi L*, quasi a* and dermal thickness) were measured during the study period. Result showed that the L* value of Chromameter(®) , Melanin index (M.I.) of Mexameter(®) and quasi L* value obtained by image analysis improved with statistical significance after applying the test product compared with the placebo product. CONCLUSION: We classified the dark circles according to the causes of the dark circles and verified the reliability of the parameter obtained by the instrument conformity assessment used in this study through the efficacy evaluation. Also based on this study, we were to suggest newly established methods which can be applied to the evaluation of efficacy of functional cosmetics for dark circles.
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Colorimetría/métodos , Dermoscopía/métodos , Enfermedades de los Párpados/clasificación , Enfermedades de los Párpados/diagnóstico , Párpados/anomalías , Hiperpigmentación/clasificación , Hiperpigmentación/diagnóstico , Anamnesis/métodos , Examen Físico/métodos , Adulto , Diagnóstico Diferencial , Técnicas de Diagnóstico Oftalmológico , Método Doble Ciego , Dermatosis Facial/clasificación , Dermatosis Facial/diagnóstico , Femenino , Humanos , Persona de Mediana Edad , Variaciones Dependientes del Observador , Efecto Placebo , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Adulto JovenRESUMEN
OBJECTIVE: The physiological characteristics of the skin are varied greatly, depending on gender, age, region and race, and many dermatologic researches have been performed through various research methods. This study aimed to examine how Korean men's skin conditions were influenced by temperature or humidity changes caused by seasonal rotations. METHODS: A total of 100 healthy Korean men, age range 20-59 years, participated in the study for both summer and winter. We compared on the characteristics of skin between summer and winter. The skin hydration, skin pH and TEWL were evaluated on the forehead, cheek and forearm. The skin sebum content of the glabella, nasal ala and cheek was measured using Sebumeter(®) (SM810, Courage+Khazaka, Germany). Cutometer(®) (MPA 580 Courage+Khazaka, Germany) the elasticity was measured by on the cheeks, and PRIMOS lite(®) (Phase shift Rapid in vivo Measurement of Skin, GFMesstechnik GmbH, Germany) was used to evaluate wrinkles on crow's feet. Lastly, in addition, the skin pore of the face was measured using the Janus(®) (PSI, Korea) which is a facial analysis system. RESULTS: The results were as follows: the comparison of hydration in summer and winter shows significant differences in their forehead, cheeks and forearm. The pH values of the skin surface were generally higher in winter, and significantly different on each site, and the sebum content was higher in summer than in winter. As a result of the pore measurement, the summer showed more pores compared to the winter, and there was a statistically significant difference in skin pores between summer and winter. The sensitivity measured by stinging test increases significantly more in winter than in summer. However, there were no seasonal differences in wrinkles and skin brightness. CONCLUSION: The skin surface pH, TEWL, sebum content, hydration, elasticity, wrinkles, skin pore and skin sensitivity vary with seasons and body regions in Korean men.
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Estaciones del Año , Fenómenos Fisiológicos de la Piel , Adulto , Humanos , Concentración de Iones de Hidrógeno , Masculino , Persona de Mediana Edad , República de Corea , Adulto JovenRESUMEN
BACKGROUND: Invasive pulmonary aspergillosis (IPA) is a rare complication with a high mortality rate after organ transplantation. Early antifungal therapy improves survival. In some cases, surgical resection is necessary for a complete remission. We have reported herein a case of sustained (but stationary) IPA cured by the modulation of immunosuppression with discontinuation of antifungal therapy. CASE: A 34-year-old man underwent liver transplantation experiencing are early bile leak and an acute rejection episode. Steroid pulse therapy was accompanied by intensified immunosuppression. After a week he developed intermittent hemoptysis, which was treated with antibiotics due to a diagnosis of pneumonia by chest X ray. Meanwhile the bile leak progressed to a huge biloma at reoperation 3 weeks after the initial operation he was converted from a choledochocholedochostomy to a hepaticojejunostomy. After 1 week, follow-up chest X ray showed the lesion had progressed to form an abscess. Subsequent chest computed tomography (CT) detected a pulmonary mass with internal necrosis and CT-guided lung biopsy revealed Aspergillus fumigatus on isolation. Antifungal therapy with voriconazole and/or amphotericin B for 3 months stopped disease progression but the lesion was sustained. We stopped antifungal therapy due to side effects and reduced the intensity of immunosuppression. Follow-up chest CT 5 months later showed improvement with a persistent cavitary lesion containing a fungal ball. However, after 9 months, there was no focal lesion in either lung. This unusual case of IPA was cured by reducing immunosuppression without antifungal therapy. CONCLUSION: IPA should be eradicated with prompt antifugal therapy, but stationary IPA can be observed cautiously while reducing immunosuppression.
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Antifúngicos/uso terapéutico , Inmunosupresores/administración & dosificación , Aspergilosis Pulmonar Invasiva/tratamiento farmacológico , Trasplante de Hígado/efectos adversos , Donadores Vivos , Adulto , Antifúngicos/efectos adversos , Quimioterapia Combinada , Humanos , Aspergilosis Pulmonar Invasiva/diagnóstico por imagen , Aspergilosis Pulmonar Invasiva/microbiología , Masculino , Ácido Micofenólico/administración & dosificación , Ácido Micofenólico/análogos & derivados , Esteroides/administración & dosificación , Tacrolimus/administración & dosificación , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
Mesenchymal stem cells (MSCs) have been used with success in several clinical applications for clinical treatment of ischemic hearts. However, the reported effects of MSC-based therapy on myocardial infarction (MI) are inconsistent. In particular, the preventive effects of MSC-based therapy on arrhythmic sudden death and metabolic disorders after infarction remain controversial. Here, we investigated the effects of MSCs on reverse remodeling in an infarcted myocardium, and found that MSC-therapy failed to achieve the complete regeneration of infarcted myocardium. Histological analyses showed that although infarct size and interstitial fibrosis induced by MI recovered significantly after MSC treatment, these improvements were marginal, indicating that a significant amount of damaged tissue was still present. Furthermore, transplanted MSCs had slight anti-apoptotic and anti-inflammatory effects in MSC-implanted regions and no significant improvements in cardiac function were observed, suggesting that naïve MSCs might not be the right cell type to treat myocardial infarction. Furthermore, small ion profiling using ToF-SIMS revealed that the metabolic stabilization provided by the MSCs implantation was not significant compared to the sham group. Together, these results indicate that pretreatment of MSCs is needed to enhance the benefits of MSCs, particularly when MSCs are used to treat arrhythmogenicity and metabolically stabilize infarcted myocardium.
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Corazón/fisiopatología , Trasplante de Células Madre Mesenquimatosas , Modelos Cardiovasculares , Infarto del Miocardio/terapia , Animales , Citocinas/análisis , Modelos Animales de Enfermedad , Pruebas de Función Cardíaca/métodos , Etiquetado Corte-Fin in Situ/métodos , Masculino , Infarto del Miocardio/metabolismo , Ratas , Ratas Sprague-Dawley , Regeneración/fisiología , Espectrometría de Masa de Ion Secundario/métodosRESUMEN
INTRODUCTION: Globally, non-alcoholic fatty liver disease (NAFLD) continues to rise and isoflavones exert antisteatotic effects by the regulation of hepatic lipogenesis/insulin resistance or adiposity/a variety of adipocytokines are related to hepatic steatosis. However, there is very little information regarding the potential effects of daidzein, the secondary abundant isoflavone, on NAFLD. Here, we have assessed the hepatic global transcription profiles, adipocytokines and adiposity in mice with high fat-induced NAFLD and their alteration by daidzein supplementation. METHODS: C57BL/6J mice were fed with normal fat (16% fat of total energy), high fat (HF; 36% fat of total energy) and HF supplemented with daidzein (0.1, 0.5, 1 and 2 g per kg diet) for 12 weeks. RESULTS: Daidzein supplementation (≥ 0.5 g per kg diet) reduced hepatic lipid concentrations and alleviated hepatic steatosis. The hepatic microarray showed that daidzein supplementation (1 g per kg diet) downregulated carbohydrate responsive element binding protein, a determinant of de novo lipogenesis, its upstream gene liver X receptor ß and its target genes encoding for lipogenic enzymes, thereby preventing hepatic steatosis and insulin resistance. These results were confirmed by lower insulin and blood glucose levels as well as homeostasis model assessment insulin resistance scores. In addition, daidzein supplementation inhibited adiposity by the upregulation of genes involved in fatty acid ß-oxidation and the antiadipogeneis, and moreover augmented antisteatohepatitic leptin and adiponectin mRNA levels, whereas it reduced the mRNA or concentration of steatotic tumor necrosis factor α and ghrelin. CONCLUSIONS: These findings show that daidzein might alleviate NAFLD through the direct regulation of hepatic de novo lipogenesis and insulin signaling, and the indirect control of adiposity and adipocytokines by the alteration of adipocyte metabolism.
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Adipocitos/efectos de los fármacos , Adipoquinas/metabolismo , Tejido Adiposo/efectos de los fármacos , Hígado Graso/prevención & control , Isoflavonas/farmacología , Lipogénesis/efectos de los fármacos , Fitoestrógenos/farmacología , Adipocitos/metabolismo , Tejido Adiposo/metabolismo , Animales , Peso Corporal , Dieta , Hígado Graso/tratamiento farmacológico , Hígado Graso/metabolismo , Perfilación de la Expresión Génica , Insulina/metabolismo , Resistencia a la Insulina , Ratones , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Clevudine shows high rates of virologic and biochemical responses in patients with chronic hepatitis B. However, the efficacy and safety of clevudine in patients with cirrhosis are unknown. The aims of this study were to evaluate the safety and to assess the virologic and the biochemical responses to clevudine in patients with cirrhosis with chronic hepatitis B virus (HBV) infection. We reviewed data from treatment-naïve patients with chronic hepatitis B with and without cirrhosis who started clevudine between April 2007 and March 2008 (n = 52, hepatitis B without cirrhosis n = 21 and chronic hepatitis B with cirrhosis n = 31) at Korea University Ansan/Guro Hospital. All of the patients were treated for more than 48 weeks. The mean age was older in the patients with cirrhosis. Baseline HBV DNA levels were 6.9 and 7.78 log copies/mL (P = 0.042), and alanine aminotransferase (ALT) levels were 104.9 and 147.4 IU/L (P = 0.204), for those with and without cirrhosis, respectively. Virologic response (HBV DNA <1000 copies/mL) (87.1%vs 71.4%, P = 0.24) and biochemical response (83.9%vs 80.9%, P = 0.99) at week 48 were not significantly different between the two groups. Early virologic response at week 12 was even higher in the patients with cirrhosis (61.3%vs 28.6%, P = 0.026). Neither ALT flare nor newly onset hepatic decompensation was found in the patients with cirrhosis, whereas ALT flare was transiently observed in 14.3% of the chronic hepatitis group. In conclusion, although clevudine may produce a transient elevation of ALT during the early treatment period, such findings were not observed in patients with cirrhosis and the virologic and biochemical responses of the groups were comparable.
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Antivirales/administración & dosificación , Arabinofuranosil Uracilo/análogos & derivados , Hepatitis B Crónica/tratamiento farmacológico , Cirrosis Hepática/tratamiento farmacológico , Adulto , Alanina Transaminasa/sangre , Antivirales/efectos adversos , Arabinofuranosil Uracilo/administración & dosificación , Arabinofuranosil Uracilo/efectos adversos , ADN Viral/sangre , Femenino , Hepatitis B Crónica/complicaciones , Humanos , Corea (Geográfico) , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Carga ViralRESUMEN
BACKGROUND AND AIMS: We compared the prevalence of adenomatous and cancerous colon polyps in patients who underwent endoscopic removal of gastric neoplasms and in healthy controls. MATERIALS AND METHODS: This retrospective study reviewed the medical records of 186 patients with gastric neoplasms and 186 healthy subjects from January 2002 to October 2008. The gastric neoplasm group was comprised of patients undergoing endoscopic removal of gastric adenomas or early gastric cancers and serial fiberoptic colonoscopy (FCS) for checkups. The control group was comprised of subjects undergoing fiberoptic esophagogastroduodenoscopy (FEGD) and FCS for general checkup and was matched for age and sex with the gastric neoplasm group. Advanced colonic neoplasm was defined by any of the following: (1) the presence of three or more polyps; (2) polyp size at least 1.0 cm; (3) high-grade dysplasia or adenocarcinoma confirmed by histopathologic examination. RESULTS: Of the 372 persons, colorectal polyps were detected in 124 (33.3 %), advanced colonic neoplasms in 44 (11.8 %), and adenocarcinomas in 10 (2.7 %). The overall prevalence of adenomatous or cancerous polyps ("all polyps") and the prevalence of advanced colonic neoplasms were significantly higher in the gastric neoplasm group than in the control group (all polyps: 40.9 % in the gastric neoplasm group vs. 25.8 % in the control group, P = 0.002; advanced colonic neoplasms: 15.6 % vs. 8.1 %, P = 0.025). The risk factors for all polyps were age, male sex, diabetes mellitus, and being assigned to the gastric neoplasm group, and those for advanced colonic neoplasms were age and being assigned to the gastric neoplasm group. Confining the analysis to the gastric neoplasm group, the risk factors for all polyps were identical with those for the total group; however, those for advanced colonic neoplasm were different (age vs. diabetes and hypertriglyceridemia). CONCLUSION: Endoscopists should consider performing routine FCS in patients undergoing endoscopic removal of gastric neoplasms.
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Adenoma/cirugía , Pólipos del Colon/epidemiología , Gastrectomía/métodos , Gastroscopía/métodos , Neoplasias Gástricas/cirugía , Adenoma/complicaciones , Pólipos del Colon/complicaciones , Femenino , Estudios de Seguimiento , Humanos , Corea (Geográfico)/epidemiología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Prevalencia , Estudios Retrospectivos , Neoplasias Gástricas/complicaciones , Neoplasias Gástricas/diagnósticoRESUMEN
Transcatheter arterial chemoembolization is one of the most common treatment modalities for hepatocellular carcinoma. Transcatheter arterial chemoembolization is considered to be a relatively safe procedure, but transcatheter arterial chemoembolization is associated with a number of disastrous complications. Among the ischaemic complications caused by transcatheter arterial chemoembolization, spinal cord injury is very rare, but can occur via the intercostal or lumbar arteries. We report two cases of extremely rare spinal cord injuries after transcatheter arterial chemoembolization in patients with hepatocellular carcinoma. The patients had sensory loss below the T9 or T10 dermatomes and paraparesis or paraplegia within 6-8h after transcatheter arterial chemoembolization. One patient sustained paraplegia until death 2 months after transcatheter arterial chemoembolization and the other patient recovered almost completely 2 months after transcatheter arterial chemoembolization.
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Carcinoma Hepatocelular/terapia , Cateterismo Periférico/efectos adversos , Quimioembolización Terapéutica/efectos adversos , Neoplasias Hepáticas/terapia , Traumatismos de la Médula Espinal/etiología , Anciano , Quimioembolización Terapéutica/métodos , Humanos , Masculino , Persona de Mediana Edad , Paraplejía/etiologíaRESUMEN
OBJECTIVE: To report a case of a patient with many of the common manifestations of Gorlin's syndrome, a rare inherited condition. CLINICAL PRESENTATION AND INTERVENTION: A 26-year-old female with longstanding left hip pain was referred for bone scintigraphy to find the cause of pain. The findings on bone scintigraphy as well as prior radiographic studies illustrated many of the defining features of Gorlin's syndrome, i.e. jaw keratocysts, falcine calcifications, short and deformed ribs, Sprengel deformity and a sclerotic bone lesion. The past medical history also revealed dermatologic, cardiac and gynecological findings related to the syndrome. CONCLUSION: Our case highlights the multisystemic involvement of Gorlin's syndrome, based particularly on the skeletal findings. Practicing physicians, including imaging specialists, should be familiar with these findings to reach the diagnosis.
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Síndrome del Nevo Basocelular/diagnóstico por imagen , Adulto , Diagnóstico Diferencial , Femenino , Humanos , Radiografía , CintigrafíaRESUMEN
BACKGROUND: Adefovir dipivoxil (ADV) is a potent nucleotide analogue against both the wild-type and lamivudine (LMV) resistant hepatitis B virus (HBV). The cumulative incidence of ADV resistant mutations in the nucleoside/-tide treatment naive chronic hepatitis B patient (CHB) at weeks 48, 96, and 144 was 0, 0.8-3%, and approximately 5.9%, respectively. AIMS: The aim of this study was to characterise the genotypic and phenotypic mutation profiles to ADV in 67 LMV resistant CHB patients who were treated with ADV. METHODS: Serum HBV DNA was quantified by real time polymerase chain reaction. The ADV mutant was detected using matrix assisted laser desorption/ionisation time of flight mass spectrometry based genotyping assays, termed restriction fragment mass polymorphism (RFMP). RESULTS: RFMP analysis revealed that a total of 11 amino acid substitutions developed in the rt domain of the HBV polymerase in nine patients. The cumulative incidence of genotypic ADV resistance at months 12 and 24 was 6.4% and 25.4%, respectively. The rtA181V, rtN236T, and rtA181T mutations were detected in five, four, and two of the 67 patients at treatment months 12-17, 3-19, and 7-20, respectively. Serial quantification of serum HBV DNA revealed that two patients with the rtA181V mutation, with or without the rtN236T mutation, and one patient with the rtA181T mutation displayed HBV DNA rebound. CONCLUSION: Emergence of the ADV mutation in LMV resistant patients who are treated with ADV appeared to present earlier and more frequently than was reported in previous studies on nucleoside/-tide treatment naive patients.
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Adenina/análogos & derivados , Hepatitis B Crónica/tratamiento farmacológico , Lamivudine/uso terapéutico , Organofosfonatos/uso terapéutico , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Adenina/uso terapéutico , Adulto , Farmacorresistencia Viral/genética , Femenino , Genotipo , Hepatitis B Crónica/genética , Humanos , Masculino , Persona de Mediana Edad , Mutación/genética , Fenotipo , Estudios RetrospectivosRESUMEN
The purpose of this paper is 2-fold. First, we present several extensions to the ONIOM(QM:MM) scheme. In its original formulation, the electrostatic interaction between the regions is included at the classical level. Here we present the extension to electronic embedding. We show how the behavior of ONIOM with electronic embedding can be more stable than QM/MM with electronic embedding. We also investigate the link atom correction, which is implicit in ONIOM but not in QM/MM. Second, we demonstrate some of the practical aspects of ONIOM(QM:MM) calculations. Specifically, we show that the potential surface can be discontinuous when there is bond breaking and forming closer than three bonds from the MM region.
RESUMEN
We describe herein a computationally intensive project aimed at carrying out molecular dynamics (MD) simulations including water and counterions on B-DNA oligomers containing all 136 unique tetranucleotide base sequences. This initiative was undertaken by an international collaborative effort involving nine research groups, the "Ascona B-DNA Consortium" (ABC). Calculations were carried out on the 136 cases imbedded in 39 DNA oligomers with repeating tetranucleotide sequences, capped on both ends by GC pairs and each having a total length of 15 nucleotide pairs. All MD simulations were carried out using a well-defined protocol, the AMBER suite of programs, and the parm94 force field. Phase I of the ABC project involves a total of approximately 0.6 mus of simulation for systems containing approximately 24,000 atoms. The resulting trajectories involve 600,000 coordinate sets and represent approximately 400 gigabytes of data. In this article, the research design, details of the simulation protocol, informatics issues, and the organization of the results into a web-accessible database are described. Preliminary results from 15-ns MD trajectories are presented for the d(CpG) step in its 10 unique sequence contexts, and issues of stability and convergence, the extent of quasiergodic problems, and the possibility of long-lived conformational substates are discussed.
Asunto(s)
ADN/química , Modelos Químicos , Modelos Moleculares , Oligodesoxirribonucleótidos/química , Secuencia de Bases , Simulación por Computador , Cinética , Datos de Secuencia Molecular , Movimiento (Física) , Conformación de Ácido Nucleico , Relación Estructura-ActividadRESUMEN
The specificity of papilloma virus E2 protein-DNA binding depends critically upon the sequence of a region of the DNA not in direct contact with the protein, and represents one of the simplest known examples of indirect readout. A detailed characterization of this system in solution is important to the further investigation hypothesis of a structural code for DNA recognition by regulatory proteins. In the crystalline state, the E2 DNA oligonucleotide sequence, d(ACCGAATTCGGT), exhibits three different structural forms. We report herein studies of the structure of E2 DNA in solution based on a series of molecular dynamics (MD) simulations including counterions and water, utilizing both the canonical and various crystallographic structures as initial points of departure. All MDs converged on a single dynamical structure of d(ACCGAATTCGGT) in solution. The predicted structure is in close accord with two of the three crystal structures, and indicates that a significant kink in the double helix at the central ApT step in the other crystal molecule may be a packing effect. The dynamical fine structure was analyzed on the basis of helicoidal parameters. The calculated curvature in the sequence was found to originate primarily from YPR steps in the regions flanking the central AATT tract. In order to study the role of structural adaptation of the DNA in the binding process, a subsequent simulation on the 16-mer cognate sequence d(CAACCGAATTCGGTTG) was initiated from the crystallographic coordinates of the bound DNA in the crystal structure of the protein DNA complex. MD simulations starting with the protein-bound form relaxed rapidly back to the dynamical structure predicted from the previous simulations on the uncomplexed DNA. The MD results show that the bound form E2 DNA is a dynamically unstable structure in the absence of protein, and arises as a consequence of both structural changes intrinsic to the sequence and induced by the interaction with protein.
Asunto(s)
Papillomavirus Bovino 1/química , ADN Viral/química , Conformación de Ácido Nucleico , Animales , Secuencia de Bases , Papillomavirus Bovino 1/genética , Bovinos , ADN Viral/genética , Proteínas de Unión al ADN/genética , Técnicas In Vitro , Modelos Moleculares , Oligodesoxirribonucleótidos/química , Oligodesoxirribonucleótidos/genética , Soluciones , Termodinámica , Proteínas Virales/genéticaRESUMEN
We have isolated a full-length cDNA clone that encodes for a Schizosaccharomyces pombe homolog of the dual-specificity protein kinase of the LAMMER family, lkh1 (lammer kinase homolog). The proposed Lkh1 protein contains 575 amino acids. The lkh1(+) null mutant is viable, but exhibits flocculation upon reaching stationary phase in liquid media and filamentous adhesion growth on solid media. Analysis of the flocculation activity of the lkh1(+) null mutant indicates that asexual aggregation of S. pombe cells into floccules is divalent cation-dependent and galactose-specific. We also demonstrate that the Saccharomyces cerevisiae LAMMER kinase homolog, Kns1, can substitute for the Lkh1 function in S. pombe.