Primary biliary cirrhosis(PBC),which is characterised by progressive destruction of intrahepatic bile ducts,is not a rare disease since both prevalence and incidence are increasing during the last years mainly due to ...Primary biliary cirrhosis(PBC),which is characterised by progressive destruction of intrahepatic bile ducts,is not a rare disease since both prevalence and incidence are increasing during the last years mainly due to the improvement of case finding strategies.The prognosis of the disease has improved due to both the recognition of earlier and indolent cases,and to the wide use of ursodeoxycholic acid(UDCA).New indicators of prog-nosis are available that will be useful especially for the growing number of patients with less severe disease.Most patients are asymptomatic at presentation.Pruri-tus may represent the most distressing symptom and,when UDCA is ineffective,cholestyramine represents the mainstay of treatment.Complications of long-standing cholestasis may be clinically relevant only in very ad-vanced stages.Available data on the effects of UDCA on clinically relevant end points clearly indicate that the drug is able to slow but not to halt the progression of the disease while,in advanced stages,the only thera-peutic option remains liver transplantation.展开更多
Background Available data regarding clinical profile and management of elderly patients with atrial fibrillation （AF） according to dependency, fragility and cognitive impairment are scarce. The objective of the stud...Background Available data regarding clinical profile and management of elderly patients with atrial fibrillation （AF） according to dependency, fragility and cognitive impairment are scarce. The objective of the study was to analyze the biodemographic data, clinical profile and antithrombotic treatment according to dependency, fragility and cognitive impairment in elderly AF patients. Methods Cross- sectional and multi-center study performed in consecutive AF patients ≥ 75 years treated with oral anticoagulants ≥ 3 months attended in Internal Medicine Departments in Spain. Results A total of 837 patients （83.0 ± 5.0 years; CHA2DS2-VASc： 5.0 ± 1.4; HAS-BLED： 2.1 ± 0.9） were included. 44.4% of patients had some degree of dependency, 43.3% were fragile, and 32.3% had cognitive impairment. Patients with any of these conditions were older, had a worse clinical profile, with more comorbidities and higher risks of thromboembolic and bleeding events. All these conditions were independently associated among them. Overall, 70.8% of patients were taking vitamin K antagonists, the remaining 29.2% direct oral anticoagulants and 9.7% oral antiplatelets. This distribution was independent of the presence of dependency or fragility, but there was a trend to a higher prescription of vitamin K antagonists in those patients with cognitive impairment （75.2% vs. 68.8%; P = 0.05）. Conclusions Approximately 32%-44% of elderly anticoagulated AF patients attended have some degree of dependency, fragility and/or cognitive impairment. Patients with any of these conditions are older and have a worse clinical profile. Ap？proximately 71% of patients are taking vitamin K antagonists, regardless dependency or frailty, but with a trend to higher prescription in patients with cognitive impairment.展开更多
As among persons with normal anatomy, occasional patients with situs inversus develop malignant tumors. Recently, several laparoscopic operations have been reported in patients with situs inversus. We describe laparos...As among persons with normal anatomy, occasional patients with situs inversus develop malignant tumors. Recently, several laparoscopic operations have been reported in patients with situs inversus. We describe laparoscopic hemicolectomy with radical lymphadenectomy in such a patient. Careful consideration of the mirror-image anatomy permitted safe operation using techniques not otherwise differing from those in ordinary cases. Thus, curative laparoscopic surgery for colon cancer in the presence of situs inversus is feasible and safe.展开更多
AIM： TO investigate the effects of ursodeoxycholic acid （UDCA） on chenodeoxycholic acid （CDCA）-induced liver injury in hamsters, and to elucidate a correlation between liver injury and bile acid profiles in the l...AIM： TO investigate the effects of ursodeoxycholic acid （UDCA） on chenodeoxycholic acid （CDCA）-induced liver injury in hamsters, and to elucidate a correlation between liver injury and bile acid profiles in the liver.METHODS： Liver injury was induced in hamsters by administration of 0.5% （w/w） CDCA in their feed for 7 d. UDCA （50 mg/kg and 150 mg/kg） was administered for the last 3 d of the experiment.RESULTS： At the end of the experiment, serum alanine aminotransferase （ALl） increased more than 10 times and the presence of liver injury was confirmed histologically. Marked increase in bile acids was observed in the liver. The amount of total bile acids increased approximately three-fold and was accompanied by the increase in hydrophobic bile acids, CDCA and lithocholic acid （LCA）. UDCA （50 mg/kg and 150 mg/kg） improved liver histology, with a significant decrease （679.3 ±77.5 U/L vs 333.6 ± 50.4 U/L and 254.3 ±35.5 U/ L, respectively, P 〈 0.01） in serum ALT level. UDCA decreased the concentrations of the hydrophobic bile acids, and as a result, a decrease in the total bile acid level in the liver was achieved.CONCLUSION： The results show that UDCA improves oral CDCA-induced liver damage in hamsters. The protective effects of UDCA appear to result from a decrease in the concentration of hydrophobic bile acids, CDCA and LCA, which accumulate and show the cytotoxicity in the liver.展开更多
AIM: To determine clinical characteristics and treatment outcome of gastric lymphoma after chemotherapy and immuno-chemotherapy. METHODS: Thirty four patients with primary gastric mucosa associated lymphoid tissue (MA...AIM: To determine clinical characteristics and treatment outcome of gastric lymphoma after chemotherapy and immuno-chemotherapy. METHODS: Thirty four patients with primary gastric mucosa associated lymphoid tissue (MALT) lymphoma (Ann Arbor stages Ⅰ to Ⅳ) were enrolled. All had upper gastric endoscopy, abdominal ultrasonography, CT and H pylori status assessment (histology and serology). After anti-H pylori treatment and initial chemotherapy, patients were re-examined every 4 mo. RESULTS: Histological regression of the lymphoma was complete in 22/34 (64.7%) and partial in 9 (26.5%) patients. Median follow up time for these 31 responders was 60 mo (range 48-120). No regression was noted in 3 patients. Among the 25 (73.5%) H pylori positive patients, the eradication rate was 100%.CONCLUSION: Using univariate analysis, predictive factors for overall survival were international prognostic index (IPI) score, hemoglobin level, erythrocyte sedimentation rate (ESR), and platelet numbers (P < 0.005). In addition to this, Cox proportion hazard model differentiate IPI score, ESR, and platelets as predictors of survival.展开更多
Mitogen-activated protein kinases(MAPKs) are the main regulators of cellular proliferation, growth, and survival in physiological or pathological conditions. Aberrant MAPK signaling plays a pivotal role in carcinogene...Mitogen-activated protein kinases(MAPKs) are the main regulators of cellular proliferation, growth, and survival in physiological or pathological conditions. Aberrant MAPK signaling plays a pivotal role in carcinogenesis, which leads to development and progression of human cancer. Dual-specificity phosphatase 6(DUSP6), a member of the MAPK phosphatase family, interacts with specifically targeted extracellular signal-regulated kinase 1/2 via negative feedback regulation in the MAPK pathway of mammalian cells. This phosphatase functions in a dual manner, pro-oncogenic or tumor-suppressive, depending on the type of cancer. To date, the tumor-suppressive role of DUSP6 has been demonstrated in pancreatic cancer, non-small cell lung cancer, esophageal squamous cell and nasopharyngeal carcinoma, and ovarian cancer. Its pro-oncogenic role has been observed in human glioblastoma, thyroid carcinoma, breast cancer, and acute myeloid carcinoma. Both roles of DUSP6 have been documented in malignant melanoma depending on the histological subtype of the cancer. Loss-or gain-of-function effects of DUSP6 in these cancers highlights the significance of this phosphatase in carcinogenesis. Development of methods that use the DUSP6 gene as a therapeutic target for cancer treatment or as a prognostic factor for diagnosis and evaluation of cancer treatment outcome has great potential. This review focuses on molecular characteristics of the DUSP6 gene and its role in cancers in the purview of development, progression, and cancer treatment outcome.展开更多
Patients with alcoholic liver disease frequently exhibit increased body iron stores, as reflected by elevated serum iron indices (transferrin saturation, ferritin) and hepatic iron concentration. Even mild to moderate...Patients with alcoholic liver disease frequently exhibit increased body iron stores, as reflected by elevated serum iron indices (transferrin saturation, ferritin) and hepatic iron concentration. Even mild to moderate alcohol consumption has been shown to increase the prevalence of iron overload. Moreover, increased hepatic iron content is associated with greater mortality from alcoholic cirrhosis, suggesting a pathogenic role for iron in alcoholic liver disease. Alcohol increases the severity of disease in patients with genetic hemochromatosis, an iron overload disorder common in the Caucasian population. Both iron and alcohol individually cause oxidative stress and lipid peroxidation, which culminates in liver injury. Despite these observations, the underlying mechanisms of iron accumulation and the source of the excess iron observed in alcoholic liver disease remain unclear. Over the last decade, several novel iron-regulatory proteins have been identified and these have greatly enhanced our understanding of iron metabolism. For example, hepcidin, a circulatory antimicrobial peptide synthesized by the hepatocytes of the liver is now known to play a central role in the regulation of iron homeostasis. This review attempts to describe the interaction of alcohol and iron-regulatory molecules. Understanding these molecular mechanisms is of considerable clinical importance because both alcoholic liver disease and genetic hemochromatosis are common diseases, in which alcohol and iron appear to act synergistically to cause liver injury.展开更多
文摘Primary biliary cirrhosis(PBC),which is characterised by progressive destruction of intrahepatic bile ducts,is not a rare disease since both prevalence and incidence are increasing during the last years mainly due to the improvement of case finding strategies.The prognosis of the disease has improved due to both the recognition of earlier and indolent cases,and to the wide use of ursodeoxycholic acid(UDCA).New indicators of prog-nosis are available that will be useful especially for the growing number of patients with less severe disease.Most patients are asymptomatic at presentation.Pruri-tus may represent the most distressing symptom and,when UDCA is ineffective,cholestyramine represents the mainstay of treatment.Complications of long-standing cholestasis may be clinically relevant only in very ad-vanced stages.Available data on the effects of UDCA on clinically relevant end points clearly indicate that the drug is able to slow but not to halt the progression of the disease while,in advanced stages,the only thera-peutic option remains liver transplantation.
文摘Background Available data regarding clinical profile and management of elderly patients with atrial fibrillation （AF） according to dependency, fragility and cognitive impairment are scarce. The objective of the study was to analyze the biodemographic data, clinical profile and antithrombotic treatment according to dependency, fragility and cognitive impairment in elderly AF patients. Methods Cross- sectional and multi-center study performed in consecutive AF patients ≥ 75 years treated with oral anticoagulants ≥ 3 months attended in Internal Medicine Departments in Spain. Results A total of 837 patients （83.0 ± 5.0 years; CHA2DS2-VASc： 5.0 ± 1.4; HAS-BLED： 2.1 ± 0.9） were included. 44.4% of patients had some degree of dependency, 43.3% were fragile, and 32.3% had cognitive impairment. Patients with any of these conditions were older, had a worse clinical profile, with more comorbidities and higher risks of thromboembolic and bleeding events. All these conditions were independently associated among them. Overall, 70.8% of patients were taking vitamin K antagonists, the remaining 29.2% direct oral anticoagulants and 9.7% oral antiplatelets. This distribution was independent of the presence of dependency or fragility, but there was a trend to a higher prescription of vitamin K antagonists in those patients with cognitive impairment （75.2% vs. 68.8%; P = 0.05）. Conclusions Approximately 32%-44% of elderly anticoagulated AF patients attended have some degree of dependency, fragility and/or cognitive impairment. Patients with any of these conditions are older and have a worse clinical profile. Ap？proximately 71% of patients are taking vitamin K antagonists, regardless dependency or frailty, but with a trend to higher prescription in patients with cognitive impairment.
文摘As among persons with normal anatomy, occasional patients with situs inversus develop malignant tumors. Recently, several laparoscopic operations have been reported in patients with situs inversus. We describe laparoscopic hemicolectomy with radical lymphadenectomy in such a patient. Careful consideration of the mirror-image anatomy permitted safe operation using techniques not otherwise differing from those in ordinary cases. Thus, curative laparoscopic surgery for colon cancer in the presence of situs inversus is feasible and safe.
文摘AIM： TO investigate the effects of ursodeoxycholic acid （UDCA） on chenodeoxycholic acid （CDCA）-induced liver injury in hamsters, and to elucidate a correlation between liver injury and bile acid profiles in the liver.METHODS： Liver injury was induced in hamsters by administration of 0.5% （w/w） CDCA in their feed for 7 d. UDCA （50 mg/kg and 150 mg/kg） was administered for the last 3 d of the experiment.RESULTS： At the end of the experiment, serum alanine aminotransferase （ALl） increased more than 10 times and the presence of liver injury was confirmed histologically. Marked increase in bile acids was observed in the liver. The amount of total bile acids increased approximately three-fold and was accompanied by the increase in hydrophobic bile acids, CDCA and lithocholic acid （LCA）. UDCA （50 mg/kg and 150 mg/kg） improved liver histology, with a significant decrease （679.3 ±77.5 U/L vs 333.6 ± 50.4 U/L and 254.3 ±35.5 U/ L, respectively, P 〈 0.01） in serum ALT level. UDCA decreased the concentrations of the hydrophobic bile acids, and as a result, a decrease in the total bile acid level in the liver was achieved.CONCLUSION： The results show that UDCA improves oral CDCA-induced liver damage in hamsters. The protective effects of UDCA appear to result from a decrease in the concentration of hydrophobic bile acids, CDCA and LCA, which accumulate and show the cytotoxicity in the liver.
基金Supported by Ministry of Science, Project No. 145061
文摘AIM: To determine clinical characteristics and treatment outcome of gastric lymphoma after chemotherapy and immuno-chemotherapy. METHODS: Thirty four patients with primary gastric mucosa associated lymphoid tissue (MALT) lymphoma (Ann Arbor stages Ⅰ to Ⅳ) were enrolled. All had upper gastric endoscopy, abdominal ultrasonography, CT and H pylori status assessment (histology and serology). After anti-H pylori treatment and initial chemotherapy, patients were re-examined every 4 mo. RESULTS: Histological regression of the lymphoma was complete in 22/34 (64.7%) and partial in 9 (26.5%) patients. Median follow up time for these 31 responders was 60 mo (range 48-120). No regression was noted in 3 patients. Among the 25 (73.5%) H pylori positive patients, the eradication rate was 100%.CONCLUSION: Using univariate analysis, predictive factors for overall survival were international prognostic index (IPI) score, hemoglobin level, erythrocyte sedimentation rate (ESR), and platelet numbers (P < 0.005). In addition to this, Cox proportion hazard model differentiate IPI score, ESR, and platelets as predictors of survival.
基金funded by a grant from Fundamental Research Grant Scheme, Ministry of Higher Education Malaysia (Grant No. 203.CIPPT.6711505)
文摘Mitogen-activated protein kinases(MAPKs) are the main regulators of cellular proliferation, growth, and survival in physiological or pathological conditions. Aberrant MAPK signaling plays a pivotal role in carcinogenesis, which leads to development and progression of human cancer. Dual-specificity phosphatase 6(DUSP6), a member of the MAPK phosphatase family, interacts with specifically targeted extracellular signal-regulated kinase 1/2 via negative feedback regulation in the MAPK pathway of mammalian cells. This phosphatase functions in a dual manner, pro-oncogenic or tumor-suppressive, depending on the type of cancer. To date, the tumor-suppressive role of DUSP6 has been demonstrated in pancreatic cancer, non-small cell lung cancer, esophageal squamous cell and nasopharyngeal carcinoma, and ovarian cancer. Its pro-oncogenic role has been observed in human glioblastoma, thyroid carcinoma, breast cancer, and acute myeloid carcinoma. Both roles of DUSP6 have been documented in malignant melanoma depending on the histological subtype of the cancer. Loss-or gain-of-function effects of DUSP6 in these cancers highlights the significance of this phosphatase in carcinogenesis. Development of methods that use the DUSP6 gene as a therapeutic target for cancer treatment or as a prognostic factor for diagnosis and evaluation of cancer treatment outcome has great potential. This review focuses on molecular characteristics of the DUSP6 gene and its role in cancers in the purview of development, progression, and cancer treatment outcome.
基金Supported by University of Nebraska Medical Center and the Alcoholic Beverage Medical Research Foundation
文摘Patients with alcoholic liver disease frequently exhibit increased body iron stores, as reflected by elevated serum iron indices (transferrin saturation, ferritin) and hepatic iron concentration. Even mild to moderate alcohol consumption has been shown to increase the prevalence of iron overload. Moreover, increased hepatic iron content is associated with greater mortality from alcoholic cirrhosis, suggesting a pathogenic role for iron in alcoholic liver disease. Alcohol increases the severity of disease in patients with genetic hemochromatosis, an iron overload disorder common in the Caucasian population. Both iron and alcohol individually cause oxidative stress and lipid peroxidation, which culminates in liver injury. Despite these observations, the underlying mechanisms of iron accumulation and the source of the excess iron observed in alcoholic liver disease remain unclear. Over the last decade, several novel iron-regulatory proteins have been identified and these have greatly enhanced our understanding of iron metabolism. For example, hepcidin, a circulatory antimicrobial peptide synthesized by the hepatocytes of the liver is now known to play a central role in the regulation of iron homeostasis. This review attempts to describe the interaction of alcohol and iron-regulatory molecules. Understanding these molecular mechanisms is of considerable clinical importance because both alcoholic liver disease and genetic hemochromatosis are common diseases, in which alcohol and iron appear to act synergistically to cause liver injury.
