Insulinomas,the most common cause of hypoglycemia related to endogenous hyperinsulinism,occur in 1-4 people per million of the general population.Common autonomic symptoms of insulinoma include diaphroresis,tremor,and...Insulinomas,the most common cause of hypoglycemia related to endogenous hyperinsulinism,occur in 1-4 people per million of the general population.Common autonomic symptoms of insulinoma include diaphroresis,tremor,and palpitations,whereas neuroglycopenenic symptoms include confusion,behavioural changes,personality changes,visual disturbances,seizure,and coma.Diagnosis of suspected cases is based on standard endocrine tests,especially the prolonged fasting test.Non-invasive imaging procedures,such as computed tomography and magnetic resonance imaging,are used when a diagnosis of insulinoma has been made to localize the source of pathological insulin secretion.Invasive modalities,such as endoscopic ultrasonography and arterial stimulation venous sampling,are highly accurate in the preoperative localization of insulinomas and have frequently been shown to be superior to noninvasive localization techniques.The range of techniques available for the localization of insulinomas means thatblind resection can be avoided.Intraoperative manual palpation of the pancreas by an experienced surgeon and intraoperative ultrasonography are both sensitive methods with which to finalize the location of insulinomas.A high proportion of patients with insulinomas can be cured with surgery.In patients with malignant insulinomas,an aggressive medical approach,including extended pancreatic resection,liver resection,liver transplantation,chemoembolization,or radiofrequency ablation,is recommended to improve both survival and quality of life.In patients with unresectable or uncontrollable insulinomas,such as malignant insulinoma of the pancreas,several techniques should be considered,including administration of ocreotide and/or continuous glucose monitoring,to prevent hypoglycemic episodes and to improve quality of life.展开更多
AIM:To assess risk factors for bleeding after gastric endoscopic submucosal dissection(ESD) and to develop preventive measures.METHODS:This retrospective study was performed in a tertiary referral center.A total of 32...AIM:To assess risk factors for bleeding after gastric endoscopic submucosal dissection(ESD) and to develop preventive measures.METHODS:This retrospective study was performed in a tertiary referral center.A total of 328 patients underwent ESD for 398 gastric neoplasms between July 2007 and June 2009.The main outcome was association between post-ESD bleeding and the following:age;sex;comorbidities;daily use of medicine potentially related to gastric injury/bleeding;location,size,and histological depth of lesions;ulceration;experience of operator coagulating the ulcer floor,and duration of operation.We also determined the relationship between the location of post-ESD bleeding and risk factors for hemorrhage.RESULTS:Univariate analysis revealed significant risk factors:tumor location [odds ratio(OR),2.86;95% CI:1.21-6.79,P=0.024],coagulator experience(OR,4.29;95% CI:1.43-12.86,P=0.009),and medicine potentially related to gastric injury/bleeding(OR,2.80;95% CI:1.14-6.90,P=0.039).Multivariate logistic regression analysis confirmed significant,independent risk factors:tumor in lower third of stomach(OR,2.47;95% CI:1.02-5.96,P=0.044),beginner coagulator(OR,3.93;95% CI:1.29-11.9,P=0.016),and medicine(OR,2.76;95% CI:1.09-6.98,P=0.032).We classif ied cases of post-ESD bleeding into two groups(bleeding at the ulcer margin vs bleeding at the center) and found that bleeding at the margin occurred more frequently with beginner coagulators compared with experts(OR,16.00;95% CI:1.22-210.59,P=0.040).CONCLUSION:Beginner coagulators,tumor in the antrum,and medicines were significant risk factors for post-ESD bleeding.Bleeding at the ulcer margin frequently occurred with beginner operators.展开更多
The human intestinal microbiome plays a major role in human health and diseases, including colorectal cancer. Colorectal carcinogenesis represents a heterogeneous process with a differing set of somatic molecular alte...The human intestinal microbiome plays a major role in human health and diseases, including colorectal cancer. Colorectal carcinogenesis represents a heterogeneous process with a differing set of somatic molecular alterations, influenced by diet, environmental and microbial exposures, and host immunity. Fusobacterium species are part of the human oral and intestinal microbiota. Metagenomic analyses have shown an enrichment of Fusobacterium nucleatum(F. nucleatum) in colorectal carcinoma tissue. Using 511 colorectal carcinomas from Japanese patients, we assessed the presence of F. nucleatum. Our results showed that the frequency of F. nucleatum positivity in the Japanese colorectal cancer was 8.6%(44/511), which was lower than that in United States cohort studies(13%). Similar to the United States studies, F. nucleatum positivityin Japanese colorectal cancers was significantly associated with microsatellite instability(MSI)-high status. Regarding the immune response in colorectal cancer, high levels of infiltrating T-cell subsets(i.e., CD3+, CD8+, CD45RO+, and FOXP3+ cells) have been associated with better patient prognosis. There is also evidence to indicate that molecular features of colorectal cancer, especially MSI, influence T-cell-mediated adaptive immunity. Concerning the association between the gut microbiome and immunity, F. nucleatum has been shown to expand myeloid-derived immune cells, which inhibit T-cell proliferation and induce T-cell apoptosis in colorectal cancer. This finding indicates that F. nucleatum possesses immunosuppressive activities by inhibiting human T-cell responses. Certain micro RNAs are induced during the macrophage inflammatory response and have the ability to regulate host-cell responses to pathogens. Micro RNA-21 increases the levels of IL-10 and prostaglandin E2, which suppress antitumor T-cell-mediated adaptive immunity through the inhibition of the antigen-presenting capacities of dendritic cells and T-cell proliferation in colorectal cancer cells. Thus, emerging evidence may 展开更多
AIM: To study the effects of obstructive jaundice on liver regeneration after partial hepatectomy. METHODS: Hepatocyte growth factor (HGF), its receptor, c-Met, vascular endothelial growth factor (VEGF) and tran...AIM: To study the effects of obstructive jaundice on liver regeneration after partial hepatectomy. METHODS: Hepatocyte growth factor (HGF), its receptor, c-Met, vascular endothelial growth factor (VEGF) and transforming growth factor-β1 (TGF-β1) mRNA expression in both liver tissue and isolated liver cells were investigated after biliary obstruction (BO) by quantitative reverse-transcription polymerase chain reaction (RT-PCR) using a LightCycler. Immunohistochemical staining for desmin and e-smooth muscle actin (α-SNA) was also studied. Regenerating liver weight and proliferating cell nuclear antigen (PCNA) labeling index, and growth factor expression were then evaluated after 70% hepatectomy with concomitant internal bUiary drainage in BO rats or sham-operated rats. RESULTS: Hepatic TGF-β1 mRNA levels increased significantly 14 days after BO, and further increased with duration of cholestasis. Meanwhile, HGF and VEGF tended to increase, but was not significant. In cell isolates, TGF-β1 mRNA was found mainly in the hepatic stellate cell (HSC) fraction. Immunohistochemical studies revealed an increased number of HSCs (desmin-positive cells) and activated HSCs (α-SMA-positive cells) in portal areas after BO. In a hepatectomy model, liver regeneration was delayed in BO rats, as compared to sham-operated rats. TGF-β1 mRNA was significantly up-regulated up to 48 h after hepatectomy, and the earlier HGF mRNA peak was lost in BO rats. CONCLUSION: BO induces HSCs proliferation and activation, leading to up-regulation of TGF-β1 mRNA and suppression of HGF mRNA in livers. These altered expression patterns may be strongly involved in delayed liver regeneration after hepatectomy with obstructive jaundice.展开更多
Field observation, petrological and geochemical characteristics of plagiogranite from Kuerti ophiolite indicate a similar origin to those in shearing zones. It isderived from partial melting of amphibolite that is dev...Field observation, petrological and geochemical characteristics of plagiogranite from Kuerti ophiolite indicate a similar origin to those in shearing zones. It isderived from partial melting of amphibolite that is developed from gabbro within the ocean layer 3 shear zone by the low-angle shearing deformation during the oceanic crustmigrating process. Zircon SHRIMP age of 372±19 Ma for the plagioganite from Kuerti ophiolite indicates that thisophiolite formed in the Devonian period and it alsorepresented the time of extension of the Kuerti backarc basin that is relevant to the northwards subduction of thePaleo-Asian oceanic crust. Therefore, the northwardssubduction of the Paleo-Asian Ocean beneath the Siberian Plate began in the early stage of the Late Paleozoic era.展开更多
AIM:To determine the effectiveness of pancreatic duct(PD) stent placement for the prevention of pancreatitis after endoscopic retrograde cholangiopancreatography(ERCP) in high risk patients.METHODS:Authors conducted a...AIM:To determine the effectiveness of pancreatic duct(PD) stent placement for the prevention of pancreatitis after endoscopic retrograde cholangiopancreatography(ERCP) in high risk patients.METHODS:Authors conducted a single-blind,randomized controlled trial to evaluate the effectiveness of a pancreatic spontaneous dislodgement stent against post-ERCP pancreatitis,including rates of spontaneous dislodgement and complications.Authors defined high risk patients as having any of the following:sphincter of Oddi dysfunction,difficult cannulation,prior history of post-ERCP pancreatitis,pre-cut sphincterotomy,pancreatic ductal biopsy,pancreatic sphincterotomy,intraductal ultrasonography,or a procedure time of more than 30 min.Patients were randomized to a stent group(n = 60) or to a non-stent group(n = 60).An abdominal radiograph was obtained daily to assessspontaneous stent dislodgement.Post-ERCP pancreatitis was diagnosed according to consensus criteria.RESULTS:The mean age(± standard deviation) was 67.4 ± 13.8 years and the male:female ratio was 68:52.In the stent group,the mean age was 66 ± 13 years and the male:female ratio was 33:27,and in the non-stent group,the mean age was 68 ± 14 years and the male:female ratio was 35:25.There were no significant differences between groups with respect to age,gender,final diagnosis,or type of endoscopic intervention.The frequency of post-ERCP pancreatitis in PD stent and non-stent groups was 1.7%(1/60) and 13.3%(8/60),respectively.The severity of pancreatitis was mild in all cases.The frequency of post-ERCP pancreatitis in the stent group was significantly lower than in the non-stent group(P = 0.032,Fisher's exact test).The rate of hyperamylasemia were 30%(18/60) and 38.3%(23 of 60) in the stent and non-stent groups,respectively(P = 0.05,χ2 test).The placement of a PD stent was successful in all 60 patients.The rate of spontaneous dislodgement by the third day was 96.7%(58/60),and the median(range) time to dislodgement was 2.1(2-3) d.The rates of stent migration,hemorrhag展开更多
Osteomyelitis is a devastating disease caused by microbial infection of bone. While the frequency of infection following elective orthopedic surgery is low, rates of reinfection are disturbingly high. Staphylococcus a...Osteomyelitis is a devastating disease caused by microbial infection of bone. While the frequency of infection following elective orthopedic surgery is low, rates of reinfection are disturbingly high. Staphylococcus aureus is responsible for the majority of chronic osteomyelitis cases and is often considered to be incurable due to bacterial persistence deep within bone. Unfortunately, there is no consensus on clinical classifications of osteomyelitis and the ensuing treatment algorithm. Given the high patient morbidity,mortality, and economic burden caused by osteomyelitis, it is important to elucidate mechanisms of bone infection to inform novel strategies for prevention and curative treatment. Recent discoveries in this field have identified three distinct reservoirs of bacterial biofilm including: Staphylococcal abscess communities in the local soft tissue and bone marrow, glycocalyx formation on implant hardware and necrotic tissue, and colonization of the osteocyte-lacuno canalicular network(OLCN) of cortical bone. In contrast, S.aureus intracellular persistence in bone cells has not been substantiated in vivo, which challenges this mode of chronic osteomyelitis. There have also been major advances in our understanding of the immune proteome against S. aureus, from clinical studies of serum antibodies and media enriched for newly synthesized antibodies(MENSA), which may provide new opportunities for osteomyelitis diagnosis, prognosis, and vaccine development. Finally, novel therapies such as antimicrobial implant coatings and antibiotic impregnated 3D-printed scaffolds represent promising strategies for preventing and managing this devastating disease. Here, we review these recent advances and highlight translational opportunities towards a cure.展开更多
Recent diagnostic and therapeutic progress for severe acute pancreatitis(SAP)remarkably decreased the casemortality rate.To further decrease the mortality rate of SAP,it is important to precisely evaluate the severity...Recent diagnostic and therapeutic progress for severe acute pancreatitis(SAP)remarkably decreased the casemortality rate.To further decrease the mortality rate of SAP,it is important to precisely evaluate the severity at an early stage,and initiate appropriate treatment as early as possible.Research Committee of Intractable Diseases of the Pancreas in Japan developed simpler criteria combining routinely available data with clinical signs.Severity can be evaluated by laboratory examinations or by clinical signs,reducing the defect values of the severity factors.Moreover,the severity criteria considered laboratory/clinical severity scores and contrastenhanced computed tomography(CE-CT)findings as independent risk factors.Thus,CE-CT scans are not necessarily required to evaluate the severity of acute pancreatitis.There was no fatal case in mild AP diagnosed by the CE-CT severity score,whereas case-mortality rate in those with SAP was 14.8%.Case-mortality of SAP that fulfilled both the laboratory/clinical and the CE-CT severity criteria was 30.8%.It is recommended,therefore,to perform CE-CT examination to clarify the prognosis in those patients who were diagnosed as SAP by laboratory/clinical severity criteria.Because the mortality rate of these patients with SAP is high,such patients should be transferred to advanced medical units.展开更多
AIM: In patients with liver cirrhosis and portal hypertension, portal hypertensive colopathy is thought to be an important cause of lower gastrointestinal hemorrhage. In this study, we evaluated the prevalence of colo...AIM: In patients with liver cirrhosis and portal hypertension, portal hypertensive colopathy is thought to be an important cause of lower gastrointestinal hemorrhage. In this study, we evaluated the prevalence of colonic mucosal changes in patients with liver cirrhosis and its clinical significance. METHODS: We evaluated the colonoscopic findings and liver function of 47 patients with liver cirrhosis over a 6-year period. The main cause of liver cirrhosis was post-viral hepatitis (68%) related to hepatitis B (6%) or C (62%) infection. All patients underwent upper gastrointestinal endoscopy to examine the presence of esophageal varices, cardiac varices, and congestive gastropathy, as well as a full colonoscopy to observe changes in colonic mucosa. Portal hypertensive colopathy was defined endoscopically in patients with vascular ectasia, redness, and blue vein. Vascular ectasia was classified into two types: type 1, solitary vascular ectasia; and type 2, diffuse vascular ectasia. RESULTS: Overall portal hypertensive colopathy was present in 31 patients (66%), including solitary vascular ectasia in 17 patients (36%), diffuse vascular ectasia in 20 patients (42%), redness in 10 patients (21%) and blue vein in 6 patients (12%). As the Child-Pugh class increased in severity, the prevalence of portal hypertensive colopathy rose. Child-Pugh class B and C were significantly associated with portal hypertensive colopathy. Portal hypertensive gastropathy, esophageal varices, ascites and hepatocellular carcinoma were not related to occurrence of portal hypertensive colopathy. Platelet count was significantly associated with portal hypertensive colopathy, but prothrombin time, serum albumin level, total bilirubin level and serum ALT level were not related to occurrence of portal hypertensive colopathy. CONCLUSION: As the Child-Pugh class worsens and platelet count decreases, the prevalence of portal hypertensive colopathy increases in patients with liver cirrhosis. A colonoscopic examination in patients with liver cirrhosis i展开更多
AIM: To clarify the relationship between the change of serum amylase level and post-ERCP pancreatitis. METHODS: Between January 1999 and December 2002, 1291 ERCP-related procedures were performed. Serum amylase concen...AIM: To clarify the relationship between the change of serum amylase level and post-ERCP pancreatitis. METHODS: Between January 1999 and December 2002, 1291 ERCP-related procedures were performed. Serum amylase concentrations were measured before the procedure and 3, 6, and 24 h afterward. The frequency and severity of post-ERCP pancreatitis and the relationship between these phenomena and the change in amylase level were estimated. RESULTS: Post-ERCP pancreatitis occurred in 47 patients (3.6%). Pancreatitis occurred in 1% of patients with normal amylase levels 3 h after ERCP, and in 1%, 5%, 20%, 31% and 39% of patients with amylase levels elevated 1-2 times, 2-3 times, 3-5 times, 5-10 times and over 10 times the upper normal limit at 3 h after ERCP, respectively (level < 2 times vs ≥ 2 times, P < 0.001). Of the 143 patients with levels higher than the normal limit at 3 h after ERCP followed by elevation at 6 h, pancreatitis occurred in 26%. In contrast, pancreatitis occurred in 9% of 45 patients with a level higher than two times the normal limit at 3 h after ERCP followed by a decrease at 6 h (26% vs 9%, P < 0.05). CONCLUSION: Post-ERCP pancreatitis is frequently associated with an increase in serum amylase level greater than twice the normal limit at 3 h after ERCP with an elevation at 6 h. A decrease in amylase level at 6 h after ERCP suggests the unlikelihood of development of post-ERCP pancreatitis.展开更多
AIM: To evaluate the efficacy of continuous regional arterial infusion therapy (CRAI) with gabexate mesilate and antibiotics for severe acute pancreatitis (SAP). METHODS: We conducted a prospective study on pati...AIM: To evaluate the efficacy of continuous regional arterial infusion therapy (CRAI) with gabexate mesilate and antibiotics for severe acute pancreatitis (SAP). METHODS: We conducted a prospective study on patients who developed SAP with or without CRAI. Out of 18 patients fulfilled clinical diagnostic criteria for SAP in Japan, 9 patients underwent CRAI, while 9 patients underwent conventional systemic protease inhibitor and antibiotics therapy (non-CRAI). CRAI was initiated within 72 h of the onset of pancreatitis. Gabexate mesilate (2400 mg/d) was continuously administered for 3 to 5 d. The clinical outcome including serum inflammation-related parameters were examined. RESULTS- The duration of abdominal pain in the CRAI group was 1.9 =1:0.26 d, whereas that in the non-CRAI group was 4.3 ±0.50. The duration of SIRS in the CRAI group was 2.2 ± 0.22 d, whereas that in the non- CRAI group was 3.2 ± 0.28. Abdominal pain and SIRS disappeared significantly in a short period of time after the initiation of CRAI using gabexate mesilate. The average length of hospitalization significantly differed between the CRAI and non-CRAI groups, 53.3 ± 7.9 d and 87.4± 13.9 d, respectively. During the first two weeks, levels of serum CRP and the IL6/IL10 ratio in the CRAI group tended to have a rapid decrease compared to those in the non-CRAI group. CONCLUSION: The present results suggest that CRAI using gabexate mesilate was effective against SAP.展开更多
基金Supported by Kochi Organization for Medical Reformation and Renewal Fundthe support of SatoshiIto and Kazuhiro Hanazaki(Kochi Medical School)
文摘Insulinomas,the most common cause of hypoglycemia related to endogenous hyperinsulinism,occur in 1-4 people per million of the general population.Common autonomic symptoms of insulinoma include diaphroresis,tremor,and palpitations,whereas neuroglycopenenic symptoms include confusion,behavioural changes,personality changes,visual disturbances,seizure,and coma.Diagnosis of suspected cases is based on standard endocrine tests,especially the prolonged fasting test.Non-invasive imaging procedures,such as computed tomography and magnetic resonance imaging,are used when a diagnosis of insulinoma has been made to localize the source of pathological insulin secretion.Invasive modalities,such as endoscopic ultrasonography and arterial stimulation venous sampling,are highly accurate in the preoperative localization of insulinomas and have frequently been shown to be superior to noninvasive localization techniques.The range of techniques available for the localization of insulinomas means thatblind resection can be avoided.Intraoperative manual palpation of the pancreas by an experienced surgeon and intraoperative ultrasonography are both sensitive methods with which to finalize the location of insulinomas.A high proportion of patients with insulinomas can be cured with surgery.In patients with malignant insulinomas,an aggressive medical approach,including extended pancreatic resection,liver resection,liver transplantation,chemoembolization,or radiofrequency ablation,is recommended to improve both survival and quality of life.In patients with unresectable or uncontrollable insulinomas,such as malignant insulinoma of the pancreas,several techniques should be considered,including administration of ocreotide and/or continuous glucose monitoring,to prevent hypoglycemic episodes and to improve quality of life.
文摘AIM:To assess risk factors for bleeding after gastric endoscopic submucosal dissection(ESD) and to develop preventive measures.METHODS:This retrospective study was performed in a tertiary referral center.A total of 328 patients underwent ESD for 398 gastric neoplasms between July 2007 and June 2009.The main outcome was association between post-ESD bleeding and the following:age;sex;comorbidities;daily use of medicine potentially related to gastric injury/bleeding;location,size,and histological depth of lesions;ulceration;experience of operator coagulating the ulcer floor,and duration of operation.We also determined the relationship between the location of post-ESD bleeding and risk factors for hemorrhage.RESULTS:Univariate analysis revealed significant risk factors:tumor location [odds ratio(OR),2.86;95% CI:1.21-6.79,P=0.024],coagulator experience(OR,4.29;95% CI:1.43-12.86,P=0.009),and medicine potentially related to gastric injury/bleeding(OR,2.80;95% CI:1.14-6.90,P=0.039).Multivariate logistic regression analysis confirmed significant,independent risk factors:tumor in lower third of stomach(OR,2.47;95% CI:1.02-5.96,P=0.044),beginner coagulator(OR,3.93;95% CI:1.29-11.9,P=0.016),and medicine(OR,2.76;95% CI:1.09-6.98,P=0.032).We classif ied cases of post-ESD bleeding into two groups(bleeding at the ulcer margin vs bleeding at the center) and found that bleeding at the margin occurred more frequently with beginner coagulators compared with experts(OR,16.00;95% CI:1.22-210.59,P=0.040).CONCLUSION:Beginner coagulators,tumor in the antrum,and medicines were significant risk factors for post-ESD bleeding.Bleeding at the ulcer margin frequently occurred with beginner operators.
基金Supported by Japanese Society of Gastroenterology Research Foundation(to Nosho K)Pancreas Research Foundation of Japan(to Nosho K)+4 种基金Medical Research Encouragement Prize of The Japan Medical Association(to Nosho K)The Japan Society for the Promotion of Science Challenging Exploratory Researchgrant No.25670371(to Shinomura Y)Ono Cancer Research Foundation(to Ito M)
文摘The human intestinal microbiome plays a major role in human health and diseases, including colorectal cancer. Colorectal carcinogenesis represents a heterogeneous process with a differing set of somatic molecular alterations, influenced by diet, environmental and microbial exposures, and host immunity. Fusobacterium species are part of the human oral and intestinal microbiota. Metagenomic analyses have shown an enrichment of Fusobacterium nucleatum(F. nucleatum) in colorectal carcinoma tissue. Using 511 colorectal carcinomas from Japanese patients, we assessed the presence of F. nucleatum. Our results showed that the frequency of F. nucleatum positivity in the Japanese colorectal cancer was 8.6%(44/511), which was lower than that in United States cohort studies(13%). Similar to the United States studies, F. nucleatum positivityin Japanese colorectal cancers was significantly associated with microsatellite instability(MSI)-high status. Regarding the immune response in colorectal cancer, high levels of infiltrating T-cell subsets(i.e., CD3+, CD8+, CD45RO+, and FOXP3+ cells) have been associated with better patient prognosis. There is also evidence to indicate that molecular features of colorectal cancer, especially MSI, influence T-cell-mediated adaptive immunity. Concerning the association between the gut microbiome and immunity, F. nucleatum has been shown to expand myeloid-derived immune cells, which inhibit T-cell proliferation and induce T-cell apoptosis in colorectal cancer. This finding indicates that F. nucleatum possesses immunosuppressive activities by inhibiting human T-cell responses. Certain micro RNAs are induced during the macrophage inflammatory response and have the ability to regulate host-cell responses to pathogens. Micro RNA-21 increases the levels of IL-10 and prostaglandin E2, which suppress antitumor T-cell-mediated adaptive immunity through the inhibition of the antigen-presenting capacities of dendritic cells and T-cell proliferation in colorectal cancer cells. Thus, emerging evidence may
文摘AIM: To study the effects of obstructive jaundice on liver regeneration after partial hepatectomy. METHODS: Hepatocyte growth factor (HGF), its receptor, c-Met, vascular endothelial growth factor (VEGF) and transforming growth factor-β1 (TGF-β1) mRNA expression in both liver tissue and isolated liver cells were investigated after biliary obstruction (BO) by quantitative reverse-transcription polymerase chain reaction (RT-PCR) using a LightCycler. Immunohistochemical staining for desmin and e-smooth muscle actin (α-SNA) was also studied. Regenerating liver weight and proliferating cell nuclear antigen (PCNA) labeling index, and growth factor expression were then evaluated after 70% hepatectomy with concomitant internal bUiary drainage in BO rats or sham-operated rats. RESULTS: Hepatic TGF-β1 mRNA levels increased significantly 14 days after BO, and further increased with duration of cholestasis. Meanwhile, HGF and VEGF tended to increase, but was not significant. In cell isolates, TGF-β1 mRNA was found mainly in the hepatic stellate cell (HSC) fraction. Immunohistochemical studies revealed an increased number of HSCs (desmin-positive cells) and activated HSCs (α-SMA-positive cells) in portal areas after BO. In a hepatectomy model, liver regeneration was delayed in BO rats, as compared to sham-operated rats. TGF-β1 mRNA was significantly up-regulated up to 48 h after hepatectomy, and the earlier HGF mRNA peak was lost in BO rats. CONCLUSION: BO induces HSCs proliferation and activation, leading to up-regulation of TGF-β1 mRNA and suppression of HGF mRNA in livers. These altered expression patterns may be strongly involved in delayed liver regeneration after hepatectomy with obstructive jaundice.
基金supported by the State Key Basic Research Development Program(Grant No.2001CB409805)the National Natural Science Foundation of China(Grant No.40073006).
文摘Field observation, petrological and geochemical characteristics of plagiogranite from Kuerti ophiolite indicate a similar origin to those in shearing zones. It isderived from partial melting of amphibolite that is developed from gabbro within the ocean layer 3 shear zone by the low-angle shearing deformation during the oceanic crustmigrating process. Zircon SHRIMP age of 372±19 Ma for the plagioganite from Kuerti ophiolite indicates that thisophiolite formed in the Devonian period and it alsorepresented the time of extension of the Kuerti backarc basin that is relevant to the northwards subduction of thePaleo-Asian oceanic crust. Therefore, the northwardssubduction of the Paleo-Asian Ocean beneath the Siberian Plate began in the early stage of the Late Paleozoic era.
文摘AIM:To determine the effectiveness of pancreatic duct(PD) stent placement for the prevention of pancreatitis after endoscopic retrograde cholangiopancreatography(ERCP) in high risk patients.METHODS:Authors conducted a single-blind,randomized controlled trial to evaluate the effectiveness of a pancreatic spontaneous dislodgement stent against post-ERCP pancreatitis,including rates of spontaneous dislodgement and complications.Authors defined high risk patients as having any of the following:sphincter of Oddi dysfunction,difficult cannulation,prior history of post-ERCP pancreatitis,pre-cut sphincterotomy,pancreatic ductal biopsy,pancreatic sphincterotomy,intraductal ultrasonography,or a procedure time of more than 30 min.Patients were randomized to a stent group(n = 60) or to a non-stent group(n = 60).An abdominal radiograph was obtained daily to assessspontaneous stent dislodgement.Post-ERCP pancreatitis was diagnosed according to consensus criteria.RESULTS:The mean age(± standard deviation) was 67.4 ± 13.8 years and the male:female ratio was 68:52.In the stent group,the mean age was 66 ± 13 years and the male:female ratio was 33:27,and in the non-stent group,the mean age was 68 ± 14 years and the male:female ratio was 35:25.There were no significant differences between groups with respect to age,gender,final diagnosis,or type of endoscopic intervention.The frequency of post-ERCP pancreatitis in PD stent and non-stent groups was 1.7%(1/60) and 13.3%(8/60),respectively.The severity of pancreatitis was mild in all cases.The frequency of post-ERCP pancreatitis in the stent group was significantly lower than in the non-stent group(P = 0.032,Fisher's exact test).The rate of hyperamylasemia were 30%(18/60) and 38.3%(23 of 60) in the stent and non-stent groups,respectively(P = 0.05,χ2 test).The placement of a PD stent was successful in all 60 patients.The rate of spontaneous dislodgement by the third day was 96.7%(58/60),and the median(range) time to dislodgement was 2.1(2-3) d.The rates of stent migration,hemorrhag
基金supported by grants from AOTrauma, Clinical Priority Program (Davos, Switzerland)NIH NIAMS (P50 AR072000 and P30 AR069655)+9 种基金supported by grants from NIH NIAMS P30 AR069655 pilotAO Trauma Research Fellowship (Davos, Switzerland)supported by grants from the NIH (R01 AR43510 and R01 AG049994)supported by grants from the NIH (P30 AR061307 and T32 AR53459)the NIH (R21 AR074571 and R21 AR073321)supported by grants from the NIH (R21 AR073321, R21 AR500710 and P30 AR06965501 Pilot)supported by grants from the NIH (R21 AI119646)supported by grants from Amedica Incsupported by grants from Bristol-Myers, Astellas, and Asahi-Kaseisupported by the Goldstein Award from the Department of Orthopaedics, University of Rochester, Rochester, NY
文摘Osteomyelitis is a devastating disease caused by microbial infection of bone. While the frequency of infection following elective orthopedic surgery is low, rates of reinfection are disturbingly high. Staphylococcus aureus is responsible for the majority of chronic osteomyelitis cases and is often considered to be incurable due to bacterial persistence deep within bone. Unfortunately, there is no consensus on clinical classifications of osteomyelitis and the ensuing treatment algorithm. Given the high patient morbidity,mortality, and economic burden caused by osteomyelitis, it is important to elucidate mechanisms of bone infection to inform novel strategies for prevention and curative treatment. Recent discoveries in this field have identified three distinct reservoirs of bacterial biofilm including: Staphylococcal abscess communities in the local soft tissue and bone marrow, glycocalyx formation on implant hardware and necrotic tissue, and colonization of the osteocyte-lacuno canalicular network(OLCN) of cortical bone. In contrast, S.aureus intracellular persistence in bone cells has not been substantiated in vivo, which challenges this mode of chronic osteomyelitis. There have also been major advances in our understanding of the immune proteome against S. aureus, from clinical studies of serum antibodies and media enriched for newly synthesized antibodies(MENSA), which may provide new opportunities for osteomyelitis diagnosis, prognosis, and vaccine development. Finally, novel therapies such as antimicrobial implant coatings and antibiotic impregnated 3D-printed scaffolds represent promising strategies for preventing and managing this devastating disease. Here, we review these recent advances and highlight translational opportunities towards a cure.
基金Supported by A Grant-in-Aid to the Research Committee on Intractable Pancreatic Diseases provided from the Ministry of HealthLabour and Welfare of Japan
文摘Recent diagnostic and therapeutic progress for severe acute pancreatitis(SAP)remarkably decreased the casemortality rate.To further decrease the mortality rate of SAP,it is important to precisely evaluate the severity at an early stage,and initiate appropriate treatment as early as possible.Research Committee of Intractable Diseases of the Pancreas in Japan developed simpler criteria combining routinely available data with clinical signs.Severity can be evaluated by laboratory examinations or by clinical signs,reducing the defect values of the severity factors.Moreover,the severity criteria considered laboratory/clinical severity scores and contrastenhanced computed tomography(CE-CT)findings as independent risk factors.Thus,CE-CT scans are not necessarily required to evaluate the severity of acute pancreatitis.There was no fatal case in mild AP diagnosed by the CE-CT severity score,whereas case-mortality rate in those with SAP was 14.8%.Case-mortality of SAP that fulfilled both the laboratory/clinical and the CE-CT severity criteria was 30.8%.It is recommended,therefore,to perform CE-CT examination to clarify the prognosis in those patients who were diagnosed as SAP by laboratory/clinical severity criteria.Because the mortality rate of these patients with SAP is high,such patients should be transferred to advanced medical units.
文摘AIM: In patients with liver cirrhosis and portal hypertension, portal hypertensive colopathy is thought to be an important cause of lower gastrointestinal hemorrhage. In this study, we evaluated the prevalence of colonic mucosal changes in patients with liver cirrhosis and its clinical significance. METHODS: We evaluated the colonoscopic findings and liver function of 47 patients with liver cirrhosis over a 6-year period. The main cause of liver cirrhosis was post-viral hepatitis (68%) related to hepatitis B (6%) or C (62%) infection. All patients underwent upper gastrointestinal endoscopy to examine the presence of esophageal varices, cardiac varices, and congestive gastropathy, as well as a full colonoscopy to observe changes in colonic mucosa. Portal hypertensive colopathy was defined endoscopically in patients with vascular ectasia, redness, and blue vein. Vascular ectasia was classified into two types: type 1, solitary vascular ectasia; and type 2, diffuse vascular ectasia. RESULTS: Overall portal hypertensive colopathy was present in 31 patients (66%), including solitary vascular ectasia in 17 patients (36%), diffuse vascular ectasia in 20 patients (42%), redness in 10 patients (21%) and blue vein in 6 patients (12%). As the Child-Pugh class increased in severity, the prevalence of portal hypertensive colopathy rose. Child-Pugh class B and C were significantly associated with portal hypertensive colopathy. Portal hypertensive gastropathy, esophageal varices, ascites and hepatocellular carcinoma were not related to occurrence of portal hypertensive colopathy. Platelet count was significantly associated with portal hypertensive colopathy, but prothrombin time, serum albumin level, total bilirubin level and serum ALT level were not related to occurrence of portal hypertensive colopathy. CONCLUSION: As the Child-Pugh class worsens and platelet count decreases, the prevalence of portal hypertensive colopathy increases in patients with liver cirrhosis. A colonoscopic examination in patients with liver cirrhosis i
文摘AIM: To clarify the relationship between the change of serum amylase level and post-ERCP pancreatitis. METHODS: Between January 1999 and December 2002, 1291 ERCP-related procedures were performed. Serum amylase concentrations were measured before the procedure and 3, 6, and 24 h afterward. The frequency and severity of post-ERCP pancreatitis and the relationship between these phenomena and the change in amylase level were estimated. RESULTS: Post-ERCP pancreatitis occurred in 47 patients (3.6%). Pancreatitis occurred in 1% of patients with normal amylase levels 3 h after ERCP, and in 1%, 5%, 20%, 31% and 39% of patients with amylase levels elevated 1-2 times, 2-3 times, 3-5 times, 5-10 times and over 10 times the upper normal limit at 3 h after ERCP, respectively (level < 2 times vs ≥ 2 times, P < 0.001). Of the 143 patients with levels higher than the normal limit at 3 h after ERCP followed by elevation at 6 h, pancreatitis occurred in 26%. In contrast, pancreatitis occurred in 9% of 45 patients with a level higher than two times the normal limit at 3 h after ERCP followed by a decrease at 6 h (26% vs 9%, P < 0.05). CONCLUSION: Post-ERCP pancreatitis is frequently associated with an increase in serum amylase level greater than twice the normal limit at 3 h after ERCP with an elevation at 6 h. A decrease in amylase level at 6 h after ERCP suggests the unlikelihood of development of post-ERCP pancreatitis.
基金Supported by Grant from the Ministry of Education, Culture, Sports, Science, and Technology, Japan, No. 20590808The Research Committee of Intractable Diseases of the Pancreas, provided by the Ministry of Health, Labour, and Welfare Japan, No. 50253448
文摘AIM: To evaluate the efficacy of continuous regional arterial infusion therapy (CRAI) with gabexate mesilate and antibiotics for severe acute pancreatitis (SAP). METHODS: We conducted a prospective study on patients who developed SAP with or without CRAI. Out of 18 patients fulfilled clinical diagnostic criteria for SAP in Japan, 9 patients underwent CRAI, while 9 patients underwent conventional systemic protease inhibitor and antibiotics therapy (non-CRAI). CRAI was initiated within 72 h of the onset of pancreatitis. Gabexate mesilate (2400 mg/d) was continuously administered for 3 to 5 d. The clinical outcome including serum inflammation-related parameters were examined. RESULTS- The duration of abdominal pain in the CRAI group was 1.9 =1:0.26 d, whereas that in the non-CRAI group was 4.3 ±0.50. The duration of SIRS in the CRAI group was 2.2 ± 0.22 d, whereas that in the non- CRAI group was 3.2 ± 0.28. Abdominal pain and SIRS disappeared significantly in a short period of time after the initiation of CRAI using gabexate mesilate. The average length of hospitalization significantly differed between the CRAI and non-CRAI groups, 53.3 ± 7.9 d and 87.4± 13.9 d, respectively. During the first two weeks, levels of serum CRP and the IL6/IL10 ratio in the CRAI group tended to have a rapid decrease compared to those in the non-CRAI group. CONCLUSION: The present results suggest that CRAI using gabexate mesilate was effective against SAP.