Purposes/Aims: We tested a randomized controlled study guided by the efficacy of a theory-based c... more Purposes/Aims: We tested a randomized controlled study guided by the efficacy of a theory-based culturally-responsive breast cancer screening education program in increasing mammogram screening among Chinese American (CA) immigrant women. This report is on the differences between women who had never been screened versus those who have been screened, in demographics, cultural and health beliefs, and intervention effect. Rationale/Conceptual Basis/Background: The Asian American Pacific Islander (AAPI) population is the fastest-growing racial/ethnic population in the U.S., and CA are the largest AAPI sub-group. Breast cancer continues to be the most commonly diagnosed cancer among CA women, however, mammogram screening remains at least 20% under the Healthy People 2020 projected goal of 81%. Women who have never been screened in their lives may respond differently to education programs compared to women who have been screened but are non-adherent with annual mammography. Methods: CA im...
The response of urea metabolic kinetics, the rate of whole-body protein breakdown, and muscle and... more The response of urea metabolic kinetics, the rate of whole-body protein breakdown, and muscle and skin protein synthesis rates to dietary protein intake (1,15 to 2.92 g/kg/d) was assessed in children with 20% to 40% total body surface area burn injury using a primed continuous infusion of lSNz-urea and L-13Cs-phenylalanine. Plasma urea concentration, production, and excretion rates increased with dietary protein intake without evidence of approaching maximum plateau values. There was no consistent evidence of urea recycling in these subjects (urea production = excretion) at any level of protein intake. The rate of appearance (Ra) of phenylalanine (an index of whole-body protein breakdown) and rate of muscle protein synthesis were independent of dietary protein, whereas there was a significant increase in skin protein synthesis with higher protein intake. We conclude that there seems to be little benefit of high protein intake on whole-body protein breakdown and muscle protein synthesis rates in these burn patients, although high-protein diets may enhance wound healing.
Journal of the American Society of Echocardiography, 2012
Background-The aim of this study was to compare two-dimensional (2D) and threedimensional (3D) me... more Background-The aim of this study was to compare two-dimensional (2D) and threedimensional (3D) methods for computing left ventricular (LV) rotation. Methods-A two-axis linear/rotary system was designed using rotary motors controlled through a digital interface, and 10 freshly harvested pig hearts were studied. Each heart was mounted on the rotary actuator with the base being rotated at different known degrees of rotation (10°, 15°, 20°, and 25°) and was passively driven by a pump with calibrated stoke volume (50 mL) at a constant rate (60 beats/min) simultaneously. Cardiac motion was scanned to acquire 2D short-axis views using a GE Vivid 7 system for assessing rotation, and 3D apical full-volume loops were acquired using a Toshiba Applio Artida ultrasound system. Full-volume 3D image loops were analyzed online with Toshiba Wall Motion Tracking software, and short-axis 2D images were analyzed offline for LV rotation in GE EchoPAC PC at corresponding LV levels. Results-At each state, both 2D and 3D echocardiography detected the changes in LV rotation but overestimated the rotation degrees. The biases for overestimation from 3D imaging were smaller compared with 2D imaging at each LV level. Both methods, when compared with each other, showed a linear correlation (r = 0.84, P < .0001). Bland-Altman comparison showed 99% of data points within range, with a constant bias between both methods (adjusted values of 3D = 1.892 + 0.964 × 3D). Conclusions-Although 3D echocardiography showed smaller bias, the results between 2D and 3D echocardiography were comparable.
Journal of the American College of Cardiology, 2010
... Authors: David J. Sahn, Zhiwen Zhou, Li Xiong, Muhammad Ashraf, Da-Yi Hu, Xaio-Nan Dai, Ya-We... more ... Authors: David J. Sahn, Zhiwen Zhou, Li Xiong, Muhammad Ashraf, Da-Yi Hu, Xaio-Nan Dai, Ya-Wei Xu, Berkley Cameron, Bill Kenny, Oregon Health & Science University, Portland, OR, Toshiba America Medical Systems, Tustin, CA ...
Journal of the American College of Cardiology, 2011
Background: We sought to test the accuracy and feasibility of a new magnetic resonance (MR) based... more Background: We sought to test the accuracy and feasibility of a new magnetic resonance (MR) based semi-automated border tracking right ventricular (RV) analysis program in pumped RV models. Methods: We studied six latex RV models that were constructed by painting liquid latex over plaster casts from porcine RVs of different sizes (30-60ml). Each RV model was connected to an MR compatible pulsatile pump and driven by delivering two different stroke volumes at a constant rate of 40 beats/min. End systolic volume and stroke volume at each state was calibrated by displacement of fluid level in a graduated cylinder. Pulsatile motion of the RV model was scanned for gradient cine stacks in short axis, sagittal and coronal planes with 1.5 T GE MR Scanner. Image data was exported as DICOM files to an offline RV analysis program embedded in Research Arena VA® (TomTec). Results: The RV Program slightly overestimated ESV (mean difference = 2.05 ± 1.35) and underestimated SV (mean difference = 3.45 ± 0.80) but showed a strongly positive linear correlation (r = 0.80 for ESV and 0.95 for SV) when compared with reference values and good inter-observer variability (Pearson correlation coefficient r = 0.92). Bland-Altman analyses show all data points within 95% confidence intervals of the difference that form the upper and lower limits of agreement. Conclusions: The new RVMR program is a user friendly semi-automated program that can be used for accurate assessment of RV volumes.
Sepsis with multisystem organ failure is a major cause of morbidity and mortality in burns. We st... more Sepsis with multisystem organ failure is a major cause of morbidity and mortality in burns. We studied the anatomic, physiologic, and metabolic changes of gut mucosa as a normal barrier against sepsis and systemic inflammatory response after burn and sepsis in the chronic porcine model. Flow probes were placed on the mesenteric and hepatic arteries and portal vein. Catheters were placed in the pulmonary artery (Swan-Ganz), aorta, superior mesenteric, and hepatic veins. After 5 days, baseline data were collected and studied after a 40%, third degree burn. They were resuscitated with Ringer&#39;s lactate solution (Parkland formula). Eighteen hours later, Escherichia coli endotoxin (100 micrograms/kg) was administered. All animals were sacrificed after 30 hr. The data were compared to a group of sham animals. Following thermal injury the cardiovascular status was stable. Endotoxin administration decreased systemic vascular resistance index and mean arterial pressure, but increased cardiac index. Mesenteric blood flow, vascular resistance, and oxygen consumption showed a transient fall after endotoxin infusion with 20, 23, and 40% reduction, respectively. These changes were associated with a rise in plasma levels of conjugated dienes. The intestinal ornithine decarboxylase activity was elevated at the end of the experiment, evidence of gut repair. Gut bacteria translocated into mesenteric lymph nodes, spleen, and burn wounds in 50% of the animals. We concluded that bacterial translocation into mesenteric lymph nodes, spleen, and wound is due to gut mucosal failure after burn trauma and sepsis. These pathophysiologic changes may be the result of mesenteric ischemia and reperfusion injury.
Cdif is the leading cause of nosocomial diarrhea. Therapeutic interventions are failing and Cdif ... more Cdif is the leading cause of nosocomial diarrhea. Therapeutic interventions are failing and Cdif now accounts for more deaths in the USA than HIV. Studies on the adaptive mucosal immune response have revealed little on mechanistic pathways or new therapeutic approaches, thus in the current study we have focused on the innate immune responses to Cdif toxins. The recently described NALP family of proteins is composed of 14 members that belong to the same superfamily as NOD-2. NALPs are a component of the inflammasome complex and play critical roles in the innate immune response by recognizing conserved pathogen-associated molecular patterns. NALP/inflammasome activation involves recruitment of the adaptor protein (ASC) and triggers caspase-1-mediated cleavage of IL-1β. A role for NALPs in intestinal homeostasis and inflammation has been suggested by recent genome studies that link mutations in NALP family members and Crohn's disease. Thus, we hypothesize that activation of the inflammasome and NALP signaling plays a role in the innate immune response to Cdif toxins. Aims: Characterize NALP expression in the mouse and human colon and in intestinal epithelial and macrophage cell lines and assess the role NALP signaling in Cdif toxin-induced injury. Methods: NALP expression was assessed via qPCR. Cdif toxin-induced NALP signaling was assessed in ASC-/-and NALP-3-/-deficient macrophages by western blotting for pro-IL-1β and processed IL-1β. In Vivo studies assessed Cdif toxin-induced intestinal injury in ASC-/-mice. Results: 10 of 14 NALP transcripts were detected in human macrophages and colonic tissue, and 8 of 14 NALPs were expressed in murine macrophages and colonic tissue. In murine and human macrophages, Cdif toxin activated the inflammasome resulting in caspase-1-dependent IL-1β processing, in a doseand time-dependent fashion. Deletion of ASC, but not NALP-3, completely abolished IL-1β processing in human and murine macrophages. In Vivo, ASC-/-mice were less susceptible to Cdif toxin-induced intestinal injury and inflammation. Conclusions: This is the first study to describe NALP expression and signaling events in intestinal immune responses. Our studies revealed that inflammasome signaling events play prominent roles in the pathogenesis of Cdif toxin induced injury. Blockade of NALP/inflammasome signaling significantly reduced Cdif-induced intestinal injury and may represent a novel therapeutic approach to managing this disease.
Currently available prognostic tools are inadequate to discern the molecular basis of the heterog... more Currently available prognostic tools are inadequate to discern the molecular basis of the heterogenic response in hepatitis C virus (HCV)-infected patients treated with the current standard of therapy. The expression and biological function of immune mediators have been shown to be critical in all phases of the immune response to HCV infection and likely therefore influence host response. Herein, a biometric multiplex serum cytokine assay was utilized to characterize the immunomodulatory effects of host response in 10 HCV patients. Serum levels of 17 cytokines were compared before and after 1 month of treatment and against controls. Overall serum cytokine levels were significantly higher in patients (P < 0.05) than controls. Additionally, viral titers decreased in all patients after 1 month of therapy, as did overall serum cytokine levels in the cohort (P < 0.05). To assess relationships between changes in cytokine levels and changes in viral titer, the cohort was divided into three statistically distinct subgroups based on changes in viral titers. Specific sets of cytokines decreased in each group: decreases in CCL4, interleukin (IL)-2, CXCL8, and IL-1β correlated with the greatest drops in viral titer, decreases in IL-5, granulocyte colony stimulating factor (G-CSF), and CCL4 correlated with moderate drops in viral titer, and only CCL2 correlated with the lowest drops in viral titer. Interestingly, decreases in CCL4 levels correlated with decreases in viral titers in all patients. CCL4 controls leukocyte influx and thus propagates inflammation. In conclusion, these data raise the possibility that characteristic changes in host response modulate the therapeutic response, demonstrating the prognostic power of serum cytokine profiling in chronic HCV.
Purpose. To test the efficacy of a culturally targeted breast cancer screening educational progra... more Purpose. To test the efficacy of a culturally targeted breast cancer screening educational program in increasing mammogram completion in Chinese-American immigrant women. Design. Randomized controlled study Setting. Chinese communities, Portland, Oregon. Subjects. From April 2010 to September 2011, 300 women were randomized to receive a theory-based, culturally targeted breast cancer screening educational intervention (n = 147) or a mammography screening brochure published by the National Cancer Institute (n = 153). Intervention. The two-part intervention consisted of group teaching with targeted, theory-based messages followed by individual counseling sessions. Measures. Mammography completion, perceived susceptibility, perceived benefits, perceived barriers, perceived cultural barriers, and demographic variables. Analysis. A 2 × 3 mixed logistic model was applied to determine odds ratio of mammogram completion. Results. Behavior changed in both groups, with a total of 170 particip...
Purposes/Aims: We tested a randomized controlled study guided by the efficacy of a theory-based c... more Purposes/Aims: We tested a randomized controlled study guided by the efficacy of a theory-based culturally-responsive breast cancer screening education program in increasing mammogram screening among Chinese American (CA) immigrant women. This report is on the differences between women who had never been screened versus those who have been screened, in demographics, cultural and health beliefs, and intervention effect. Rationale/Conceptual Basis/Background: The Asian American Pacific Islander (AAPI) population is the fastest-growing racial/ethnic population in the U.S., and CA are the largest AAPI sub-group. Breast cancer continues to be the most commonly diagnosed cancer among CA women, however, mammogram screening remains at least 20% under the Healthy People 2020 projected goal of 81%. Women who have never been screened in their lives may respond differently to education programs compared to women who have been screened but are non-adherent with annual mammography. Methods: CA im...
The response of urea metabolic kinetics, the rate of whole-body protein breakdown, and muscle and... more The response of urea metabolic kinetics, the rate of whole-body protein breakdown, and muscle and skin protein synthesis rates to dietary protein intake (1,15 to 2.92 g/kg/d) was assessed in children with 20% to 40% total body surface area burn injury using a primed continuous infusion of lSNz-urea and L-13Cs-phenylalanine. Plasma urea concentration, production, and excretion rates increased with dietary protein intake without evidence of approaching maximum plateau values. There was no consistent evidence of urea recycling in these subjects (urea production = excretion) at any level of protein intake. The rate of appearance (Ra) of phenylalanine (an index of whole-body protein breakdown) and rate of muscle protein synthesis were independent of dietary protein, whereas there was a significant increase in skin protein synthesis with higher protein intake. We conclude that there seems to be little benefit of high protein intake on whole-body protein breakdown and muscle protein synthesis rates in these burn patients, although high-protein diets may enhance wound healing.
Journal of the American Society of Echocardiography, 2012
Background-The aim of this study was to compare two-dimensional (2D) and threedimensional (3D) me... more Background-The aim of this study was to compare two-dimensional (2D) and threedimensional (3D) methods for computing left ventricular (LV) rotation. Methods-A two-axis linear/rotary system was designed using rotary motors controlled through a digital interface, and 10 freshly harvested pig hearts were studied. Each heart was mounted on the rotary actuator with the base being rotated at different known degrees of rotation (10°, 15°, 20°, and 25°) and was passively driven by a pump with calibrated stoke volume (50 mL) at a constant rate (60 beats/min) simultaneously. Cardiac motion was scanned to acquire 2D short-axis views using a GE Vivid 7 system for assessing rotation, and 3D apical full-volume loops were acquired using a Toshiba Applio Artida ultrasound system. Full-volume 3D image loops were analyzed online with Toshiba Wall Motion Tracking software, and short-axis 2D images were analyzed offline for LV rotation in GE EchoPAC PC at corresponding LV levels. Results-At each state, both 2D and 3D echocardiography detected the changes in LV rotation but overestimated the rotation degrees. The biases for overestimation from 3D imaging were smaller compared with 2D imaging at each LV level. Both methods, when compared with each other, showed a linear correlation (r = 0.84, P < .0001). Bland-Altman comparison showed 99% of data points within range, with a constant bias between both methods (adjusted values of 3D = 1.892 + 0.964 × 3D). Conclusions-Although 3D echocardiography showed smaller bias, the results between 2D and 3D echocardiography were comparable.
Journal of the American College of Cardiology, 2010
... Authors: David J. Sahn, Zhiwen Zhou, Li Xiong, Muhammad Ashraf, Da-Yi Hu, Xaio-Nan Dai, Ya-We... more ... Authors: David J. Sahn, Zhiwen Zhou, Li Xiong, Muhammad Ashraf, Da-Yi Hu, Xaio-Nan Dai, Ya-Wei Xu, Berkley Cameron, Bill Kenny, Oregon Health & Science University, Portland, OR, Toshiba America Medical Systems, Tustin, CA ...
Journal of the American College of Cardiology, 2011
Background: We sought to test the accuracy and feasibility of a new magnetic resonance (MR) based... more Background: We sought to test the accuracy and feasibility of a new magnetic resonance (MR) based semi-automated border tracking right ventricular (RV) analysis program in pumped RV models. Methods: We studied six latex RV models that were constructed by painting liquid latex over plaster casts from porcine RVs of different sizes (30-60ml). Each RV model was connected to an MR compatible pulsatile pump and driven by delivering two different stroke volumes at a constant rate of 40 beats/min. End systolic volume and stroke volume at each state was calibrated by displacement of fluid level in a graduated cylinder. Pulsatile motion of the RV model was scanned for gradient cine stacks in short axis, sagittal and coronal planes with 1.5 T GE MR Scanner. Image data was exported as DICOM files to an offline RV analysis program embedded in Research Arena VA® (TomTec). Results: The RV Program slightly overestimated ESV (mean difference = 2.05 ± 1.35) and underestimated SV (mean difference = 3.45 ± 0.80) but showed a strongly positive linear correlation (r = 0.80 for ESV and 0.95 for SV) when compared with reference values and good inter-observer variability (Pearson correlation coefficient r = 0.92). Bland-Altman analyses show all data points within 95% confidence intervals of the difference that form the upper and lower limits of agreement. Conclusions: The new RVMR program is a user friendly semi-automated program that can be used for accurate assessment of RV volumes.
Sepsis with multisystem organ failure is a major cause of morbidity and mortality in burns. We st... more Sepsis with multisystem organ failure is a major cause of morbidity and mortality in burns. We studied the anatomic, physiologic, and metabolic changes of gut mucosa as a normal barrier against sepsis and systemic inflammatory response after burn and sepsis in the chronic porcine model. Flow probes were placed on the mesenteric and hepatic arteries and portal vein. Catheters were placed in the pulmonary artery (Swan-Ganz), aorta, superior mesenteric, and hepatic veins. After 5 days, baseline data were collected and studied after a 40%, third degree burn. They were resuscitated with Ringer&#39;s lactate solution (Parkland formula). Eighteen hours later, Escherichia coli endotoxin (100 micrograms/kg) was administered. All animals were sacrificed after 30 hr. The data were compared to a group of sham animals. Following thermal injury the cardiovascular status was stable. Endotoxin administration decreased systemic vascular resistance index and mean arterial pressure, but increased cardiac index. Mesenteric blood flow, vascular resistance, and oxygen consumption showed a transient fall after endotoxin infusion with 20, 23, and 40% reduction, respectively. These changes were associated with a rise in plasma levels of conjugated dienes. The intestinal ornithine decarboxylase activity was elevated at the end of the experiment, evidence of gut repair. Gut bacteria translocated into mesenteric lymph nodes, spleen, and burn wounds in 50% of the animals. We concluded that bacterial translocation into mesenteric lymph nodes, spleen, and wound is due to gut mucosal failure after burn trauma and sepsis. These pathophysiologic changes may be the result of mesenteric ischemia and reperfusion injury.
Cdif is the leading cause of nosocomial diarrhea. Therapeutic interventions are failing and Cdif ... more Cdif is the leading cause of nosocomial diarrhea. Therapeutic interventions are failing and Cdif now accounts for more deaths in the USA than HIV. Studies on the adaptive mucosal immune response have revealed little on mechanistic pathways or new therapeutic approaches, thus in the current study we have focused on the innate immune responses to Cdif toxins. The recently described NALP family of proteins is composed of 14 members that belong to the same superfamily as NOD-2. NALPs are a component of the inflammasome complex and play critical roles in the innate immune response by recognizing conserved pathogen-associated molecular patterns. NALP/inflammasome activation involves recruitment of the adaptor protein (ASC) and triggers caspase-1-mediated cleavage of IL-1β. A role for NALPs in intestinal homeostasis and inflammation has been suggested by recent genome studies that link mutations in NALP family members and Crohn's disease. Thus, we hypothesize that activation of the inflammasome and NALP signaling plays a role in the innate immune response to Cdif toxins. Aims: Characterize NALP expression in the mouse and human colon and in intestinal epithelial and macrophage cell lines and assess the role NALP signaling in Cdif toxin-induced injury. Methods: NALP expression was assessed via qPCR. Cdif toxin-induced NALP signaling was assessed in ASC-/-and NALP-3-/-deficient macrophages by western blotting for pro-IL-1β and processed IL-1β. In Vivo studies assessed Cdif toxin-induced intestinal injury in ASC-/-mice. Results: 10 of 14 NALP transcripts were detected in human macrophages and colonic tissue, and 8 of 14 NALPs were expressed in murine macrophages and colonic tissue. In murine and human macrophages, Cdif toxin activated the inflammasome resulting in caspase-1-dependent IL-1β processing, in a doseand time-dependent fashion. Deletion of ASC, but not NALP-3, completely abolished IL-1β processing in human and murine macrophages. In Vivo, ASC-/-mice were less susceptible to Cdif toxin-induced intestinal injury and inflammation. Conclusions: This is the first study to describe NALP expression and signaling events in intestinal immune responses. Our studies revealed that inflammasome signaling events play prominent roles in the pathogenesis of Cdif toxin induced injury. Blockade of NALP/inflammasome signaling significantly reduced Cdif-induced intestinal injury and may represent a novel therapeutic approach to managing this disease.
Currently available prognostic tools are inadequate to discern the molecular basis of the heterog... more Currently available prognostic tools are inadequate to discern the molecular basis of the heterogenic response in hepatitis C virus (HCV)-infected patients treated with the current standard of therapy. The expression and biological function of immune mediators have been shown to be critical in all phases of the immune response to HCV infection and likely therefore influence host response. Herein, a biometric multiplex serum cytokine assay was utilized to characterize the immunomodulatory effects of host response in 10 HCV patients. Serum levels of 17 cytokines were compared before and after 1 month of treatment and against controls. Overall serum cytokine levels were significantly higher in patients (P < 0.05) than controls. Additionally, viral titers decreased in all patients after 1 month of therapy, as did overall serum cytokine levels in the cohort (P < 0.05). To assess relationships between changes in cytokine levels and changes in viral titer, the cohort was divided into three statistically distinct subgroups based on changes in viral titers. Specific sets of cytokines decreased in each group: decreases in CCL4, interleukin (IL)-2, CXCL8, and IL-1β correlated with the greatest drops in viral titer, decreases in IL-5, granulocyte colony stimulating factor (G-CSF), and CCL4 correlated with moderate drops in viral titer, and only CCL2 correlated with the lowest drops in viral titer. Interestingly, decreases in CCL4 levels correlated with decreases in viral titers in all patients. CCL4 controls leukocyte influx and thus propagates inflammation. In conclusion, these data raise the possibility that characteristic changes in host response modulate the therapeutic response, demonstrating the prognostic power of serum cytokine profiling in chronic HCV.
Purpose. To test the efficacy of a culturally targeted breast cancer screening educational progra... more Purpose. To test the efficacy of a culturally targeted breast cancer screening educational program in increasing mammogram completion in Chinese-American immigrant women. Design. Randomized controlled study Setting. Chinese communities, Portland, Oregon. Subjects. From April 2010 to September 2011, 300 women were randomized to receive a theory-based, culturally targeted breast cancer screening educational intervention (n = 147) or a mammography screening brochure published by the National Cancer Institute (n = 153). Intervention. The two-part intervention consisted of group teaching with targeted, theory-based messages followed by individual counseling sessions. Measures. Mammography completion, perceived susceptibility, perceived benefits, perceived barriers, perceived cultural barriers, and demographic variables. Analysis. A 2 × 3 mixed logistic model was applied to determine odds ratio of mammogram completion. Results. Behavior changed in both groups, with a total of 170 particip...
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