Chronic constipation is a common and extremely troublesome disorder that significantly reduces the quality of life,and this fact is consistent with the high rate at which health care is sought for this condition.The a...Chronic constipation is a common and extremely troublesome disorder that significantly reduces the quality of life,and this fact is consistent with the high rate at which health care is sought for this condition.The aim of this project was to develop a consensus for the diagnosis and treatment of chronic constipation and obstructed defecation.The commission presents its results in a "Question-Answer" format,including a set of graded recommendations based on a systematic review of the literature and evidence-based medicine.This section represents the consensus for the diagnosis.The history includes information relating to the onset and duration of symptoms and may reveal secondary causes of constipation.The presence of alarm symptoms and risk factors requires investigation.The physical examination should assess the presence of lesions in the anal and perianal region.The evidence does not support the routine use of blood testing and colonoscopy or barium enema for constipation.Various scoring systems are available to quantify the severity of constipation;the Constipation Severity Instrument for constipation and the obstructed defecation syndrome score for obstructed defecation are the most reliable.The Constipation-Related Quality of Life is an excellent tool for evaluating the patient's quality of life.No single test provides a pathophysiological basis for constipation.Colonic transit and anorectal manometry define the pathophysiologic subtypes.Balloon expulsion is a simple screening test for defecatory disorders,but it does not define the mechanisms.Defecography detects structural abnormalities and assesses functional parameters.Magnetic resonance imaging and/or pelvic floor sonography can further complement defecography by providing information on the movement of the pelvic floor and the organs that it supports.All these investigations are indicated to differentiate between slow transit constipation and obstructed defecation because the treatments differ between these conditions.展开更多
Receptor tyrosine kinases(RTKs)such as the epidermal growth factor receptor(EGFR)regulate cellular homeostatic processes.EGFR activates downstream signaling cascades that promote tumor cell survival,proliferation and ...Receptor tyrosine kinases(RTKs)such as the epidermal growth factor receptor(EGFR)regulate cellular homeostatic processes.EGFR activates downstream signaling cascades that promote tumor cell survival,proliferation and migration.Dysregulation of EGFR signaling as a consequence of overexpression,amplification and mutation of the EGFR gene occurs frequently in several types of cancers and many become dependent on EGFR signaling to maintain their malignant phenotypes.Consequently,concerted efforts have been mounted to develop therapeutic agents and strategies to effectively inhibit EGFR.However,limited therapeutic benefits to cancer patients have been derived from EGFR-targeted therapies.A well-documented obstacle to improved patient survival is the presence of EGFR-inhibitor resistant tumor cell variants within heterogeneous tumor cell masses.Here,we summarize the mechanisms by which tumors resist EGFR-targeted therapies and highlight the emerging role of microRNAs(miRs)as downstream effector molecules utilized by EGFR to promote tumor initiation,progression and that play a role in resistance to EGFR inhibitors.We also examine evidence supporting the utility of miRs as predictors of response to targeted therapies and novel therapeutic agents to circumvent EGFR-inhibitor resistance mechanisms.展开更多
Objective To investigate the efficacy of ursodeoxycholic acid in treatment of ischemia-reperfusion injury （IRI） in liver transplantation. Methods Eighty liver transplantation adult recipients were preoperatively enr...Objective To investigate the efficacy of ursodeoxycholic acid in treatment of ischemia-reperfusion injury （IRI） in liver transplantation. Methods Eighty liver transplantation adult recipients were preoperatively enrolled and randomized into the ursodeoxycholic acid （ UDCA ） （42 cases） and control （ 38 cases ） groups between May 2005 and June 2006. The two groups were statistically compared in liver biochemical parameters on post- transplant d 1, 7, 14, and 21. Rates of severe IRI-induced liver graft dysfunction, acute cellular rejection （ ACR ） episode, drug-induced hepatotoxicity, viral hepatitis, and recurrence of primary liver disease were measured within 3 weeks post-transplantation; and rates of vascular, biliary complications, and death were also measured within 3 months post-transplantation. Results In the UDCA group, serum levels of alanine aminotransferase （ ALT） on post-transplant d 7, 14, and 21 were significantly lower than those in the control group （ P = 0. 002,0. 030, 0. 049, respectively）. Compared with the control group, serum levels of aspartate aminotransferase （ AST） and y-Glutamyltranspeptidase （ GGT） on d 7 were also lower in the UDCA group （ P =0. 012 and 0. 025）. The cases of severe IRI- induced liver graft dysfunction in the UDCA group were significantly fewer than those in the control group （ 17. 5% vs. 26.3%, P =0. 048）. There were no significant differences in rates of ACR episode, histological Banff grading, or drug-induced hepatotoxicity within 3 weeks post-transplantation as well as rates of vascular, biliary complications, and death within 3 months post-transplantation between the two groups. We did not find any case of viral hepatitis or recurrence of primary liver disease in the study. Conclusion UDCA treatment can improve graft IRI early after liver transplantation. It significantly decreased serum ALT level and incidence of severe IRl-induced liver dysfunction within post-transplant 3 weeks. Cytoprection of hepatocytes by UDCA was more outstanding than that of bile duct when cold ischemia time was beneath 12 h. Vascular and biliary complications within 3 months post-transplantation can not be affected by UDCA administration in the study.展开更多
Charlotte Beradt collected hundreds of dreams she gathered in Germany between 1933 and 1939, hid them, and then sent them abroad. According to her The Third Reich of Dreams, people living under the totalitarian govern...Charlotte Beradt collected hundreds of dreams she gathered in Germany between 1933 and 1939, hid them, and then sent them abroad. According to her The Third Reich of Dreams, people living under the totalitarian government of Nazi Germany had fears of listening devices picking up their own thoughts even when they were asleep, of having no walls, and of being condemned for talking in their sleep. The dreams reveal fears, insecurities, confusion, guilt, and lack of trust. Dream research has often been impaired because researchers were examining dreams during REM ~Rapid Eye Movement） sleep, while many nightmares occur during non-REM sleep. The Beradt＇s study showed the advantage of retrospective accounts. Dreams of other trauma victims include the discovery of dead bodies and being killed oneself and often replicas of actual events. Such nightmares preclude the restorative function of sleep. Psychotherapy, however, using dreams from traumas when conducted in a safe environment, can be helpful and relieve patients from suffering.展开更多
基金Supported by Associazione Italiana Gastroenterologi and Endoscopisti Digestivi Ospedalieri via N Colajanni,4-00191 Roma,ItalySocietà Italiana di Chirurgia Colo-Rettale via Medici,23-10143Torino,Italy
文摘Chronic constipation is a common and extremely troublesome disorder that significantly reduces the quality of life,and this fact is consistent with the high rate at which health care is sought for this condition.The aim of this project was to develop a consensus for the diagnosis and treatment of chronic constipation and obstructed defecation.The commission presents its results in a "Question-Answer" format,including a set of graded recommendations based on a systematic review of the literature and evidence-based medicine.This section represents the consensus for the diagnosis.The history includes information relating to the onset and duration of symptoms and may reveal secondary causes of constipation.The presence of alarm symptoms and risk factors requires investigation.The physical examination should assess the presence of lesions in the anal and perianal region.The evidence does not support the routine use of blood testing and colonoscopy or barium enema for constipation.Various scoring systems are available to quantify the severity of constipation;the Constipation Severity Instrument for constipation and the obstructed defecation syndrome score for obstructed defecation are the most reliable.The Constipation-Related Quality of Life is an excellent tool for evaluating the patient's quality of life.No single test provides a pathophysiological basis for constipation.Colonic transit and anorectal manometry define the pathophysiologic subtypes.Balloon expulsion is a simple screening test for defecatory disorders,but it does not define the mechanisms.Defecography detects structural abnormalities and assesses functional parameters.Magnetic resonance imaging and/or pelvic floor sonography can further complement defecography by providing information on the movement of the pelvic floor and the organs that it supports.All these investigations are indicated to differentiate between slow transit constipation and obstructed defecation because the treatments differ between these conditions.
基金supported by An American Brain Tumor Association Basic Research grant to G.G.G. in memory of Keith Powers, P01-CA95616, R01-NS080939James S. McDonnell Foundation
文摘Receptor tyrosine kinases(RTKs)such as the epidermal growth factor receptor(EGFR)regulate cellular homeostatic processes.EGFR activates downstream signaling cascades that promote tumor cell survival,proliferation and migration.Dysregulation of EGFR signaling as a consequence of overexpression,amplification and mutation of the EGFR gene occurs frequently in several types of cancers and many become dependent on EGFR signaling to maintain their malignant phenotypes.Consequently,concerted efforts have been mounted to develop therapeutic agents and strategies to effectively inhibit EGFR.However,limited therapeutic benefits to cancer patients have been derived from EGFR-targeted therapies.A well-documented obstacle to improved patient survival is the presence of EGFR-inhibitor resistant tumor cell variants within heterogeneous tumor cell masses.Here,we summarize the mechanisms by which tumors resist EGFR-targeted therapies and highlight the emerging role of microRNAs(miRs)as downstream effector molecules utilized by EGFR to promote tumor initiation,progression and that play a role in resistance to EGFR inhibitors.We also examine evidence supporting the utility of miRs as predictors of response to targeted therapies and novel therapeutic agents to circumvent EGFR-inhibitor resistance mechanisms.
文摘Objective To investigate the efficacy of ursodeoxycholic acid in treatment of ischemia-reperfusion injury （IRI） in liver transplantation. Methods Eighty liver transplantation adult recipients were preoperatively enrolled and randomized into the ursodeoxycholic acid （ UDCA ） （42 cases） and control （ 38 cases ） groups between May 2005 and June 2006. The two groups were statistically compared in liver biochemical parameters on post- transplant d 1, 7, 14, and 21. Rates of severe IRI-induced liver graft dysfunction, acute cellular rejection （ ACR ） episode, drug-induced hepatotoxicity, viral hepatitis, and recurrence of primary liver disease were measured within 3 weeks post-transplantation; and rates of vascular, biliary complications, and death were also measured within 3 months post-transplantation. Results In the UDCA group, serum levels of alanine aminotransferase （ ALT） on post-transplant d 7, 14, and 21 were significantly lower than those in the control group （ P = 0. 002,0. 030, 0. 049, respectively）. Compared with the control group, serum levels of aspartate aminotransferase （ AST） and y-Glutamyltranspeptidase （ GGT） on d 7 were also lower in the UDCA group （ P =0. 012 and 0. 025）. The cases of severe IRI- induced liver graft dysfunction in the UDCA group were significantly fewer than those in the control group （ 17. 5% vs. 26.3%, P =0. 048）. There were no significant differences in rates of ACR episode, histological Banff grading, or drug-induced hepatotoxicity within 3 weeks post-transplantation as well as rates of vascular, biliary complications, and death within 3 months post-transplantation between the two groups. We did not find any case of viral hepatitis or recurrence of primary liver disease in the study. Conclusion UDCA treatment can improve graft IRI early after liver transplantation. It significantly decreased serum ALT level and incidence of severe IRl-induced liver dysfunction within post-transplant 3 weeks. Cytoprection of hepatocytes by UDCA was more outstanding than that of bile duct when cold ischemia time was beneath 12 h. Vascular and biliary complications within 3 months post-transplantation can not be affected by UDCA administration in the study.
文摘Charlotte Beradt collected hundreds of dreams she gathered in Germany between 1933 and 1939, hid them, and then sent them abroad. According to her The Third Reich of Dreams, people living under the totalitarian government of Nazi Germany had fears of listening devices picking up their own thoughts even when they were asleep, of having no walls, and of being condemned for talking in their sleep. The dreams reveal fears, insecurities, confusion, guilt, and lack of trust. Dream research has often been impaired because researchers were examining dreams during REM ~Rapid Eye Movement） sleep, while many nightmares occur during non-REM sleep. The Beradt＇s study showed the advantage of retrospective accounts. Dreams of other trauma victims include the discovery of dead bodies and being killed oneself and often replicas of actual events. Such nightmares preclude the restorative function of sleep. Psychotherapy, however, using dreams from traumas when conducted in a safe environment, can be helpful and relieve patients from suffering.
