Study Objective: To test the hypothesis that morbid obesity implies increased dz;ffulty of liver ... more Study Objective: To test the hypothesis that morbid obesity implies increased dz;ffulty of liver transplantation and increased risk of adverse outcome. Design: Retrospective review of medical records of 40 morbidly obese patients using a control cohort of patients transplanted just before and after the obese patients. Setting: University medical center. Patients: All morbidly obese patients who underwent liver transplantation over a 5% month period were included. Forty adult patients met criterion for morbid obesity with body mass index greater than 30 kg/m2. Records for 61 time-matched controls were reviewed. Measurements and Main Results: Demographic, intraoperative, and postoperative data were collected including preoperative diagnoses, laboratory and pulmonary function tests, intraoperative transfusion requirements and length of surgey, postoperative complications, and survival. Data were analyzed using Student's t-tests, and Chi-square analyses as appropriate, with significance considered a p-value less than 0.05. Obese patients were more hypoxemic than controls prior to surgery (PaO, 82.9 f 3.5 vs. 93.0 + 3.0 mmHg), were more likely to be diabetic, and had higher creatinine levels (3.0 * 0.6 vs. 1.7 + 0.2 mg/dlJ. Despite this evidence of multi-organ dysfunction, intraoperative and postoperative pulmonary and cardiac complications did not diffu between groups. Though more obese patients had prior cholecystectomy, length of surgery and intraoperative transfusion requirements were not different between groups. Obese patients did not have an increased incidence of reoperation for wound problems, and lengths of intensive care unit and hospital stays did not differ between groups. Graft and patient survival were similar in obese and nonobese liver transplant recipients. Conclusion: Morbid obesity alone does not predispose to increased complications or decreased survival afier liver transplantation.
Tumor necrosis factor stimulates DNA synthesis of mouse hepatocytes in primary culture and is sup... more Tumor necrosis factor stimulates DNA synthesis of mouse hepatocytes in primary culture and is suppressed by transforming growth factor beta and interleukin 6.
Inflammation is a normal, robust physiological process. It can also be viewed as a complex system... more Inflammation is a normal, robust physiological process. It can also be viewed as a complex system that senses and resolves homeostatic perturbations initiated from within the body (for example, in autoimmune disease) or from the outside (for example, in infections). Virtually all acute and chronic diseases are either driven or modulated by inflammation. The complex interplay between beneficial and harmful arms of the inflammatory response may underlie the lack of fully effective therapies for many diseases. Mathematical modeling is emerging as a frontline tool for understanding the complexity of the inflammatory response. A series of articles in this issue highlights various modeling approaches to inflammation in the larger context of health and disease, from intracellular signaling to whole-animal physiology. Here we discuss the state of this emerging field. We note several common features of inflammation models, as well as challenges and prospects for future studies.
Marie Csete of Emory University, Department of Anesthesiology presented a lecture on March 18, 20... more Marie Csete of Emory University, Department of Anesthesiology presented a lecture on March 18, 2003 at 11:00 am in the Suddath Seminar Room, IBB Building, Georgia Tech Campus.
Heat shock proteins (HSP) are important in neuroprotection after a variety of stresses or injurie... more Heat shock proteins (HSP) are important in neuroprotection after a variety of stresses or injuries. Both heat shock proteins and endothelin are upregulated after peripheral nerve injury, but HSP regulation after injury has not been systematically studied in peripheral nerve. The purpose of this study was to examine the regulation of small and large heat shock proteins after injury to rat sciatic nerve. Secondly, using a parallel tissue culture model for the sciatic nerve (PC12 cells), we examined potential regulation of heat shock proteins by endothelin. Western analysis of constricted, mobilized or unperturbed nerve was used to examine HSP abundance after injury. Semiquantitative PCR was used to examine heat shock message levels after nerve injury in the dorsal root ganglia. Cultured undifferentiated and differentiated PC12 cells were treated with endothelin, then western analysis of cytosol-and membrane-enriched fractions of these cells was used to examine heat shock protein regulation after endothelin treatment. Heat shock proteins are expressed at very low levels in unperturbed sciatic nerve. Constriction injury of the nerve results in increased expression of small and large heat shock proteins, but no upregulation of HSP message in corresponding dorsal root ganglia. Endothelin treatment of PC12 does not cause upregulation of heat shock proteins. Together these data show that a broad range of HSP is involved in endogenous response to peripheral nerve injury and deserve further study as potential neuroprotectants. Regulation of heat shock proteins after nerve injury is not likely due to endothelin signaling.
We examined data and patterns in clinical islet transplant studies registered on ClinicalTrials.g... more We examined data and patterns in clinical islet transplant studies registered on ClinicalTrials.gov (CTgov) for treatment of type 1 diabetes (T1D), with a goal of extracting insights to apply in the design of a pluripotent stem cell-derived islet therapy. Clinical islet transplantation, as a cell therapy (rather than solid organ transplant) is a unique precedent for stem cell-based islet therapies. Registration activity shows that the field is not growing significantly, and newer registrations suggest that the reasons for stagnation include need for a more optimal site of infusion/transplantation, and especially a need for better immune protective strategies to advance a more effective and durable therapy for T1D.
Vertebrate skeletal muscle development is characterized by tight coupling of muscle differentiati... more Vertebrate skeletal muscle development is characterized by tight coupling of muscle differentiation with cell cycle arrest in G1/G0. Key regulators of G1 progression are the G1 cyclin-dependent kinases, their positive regulators, the G1 cyclins, and their negative regulators, the cyclin-dependent kinase inhibitors (CDIs). Here we show that p27Kip1 protein, a G1 CDI, is expressed in a prominent but transient wave in the developing myotomes of the mouse embryo. We relate its expression to expression of MyoD and myogenin proteins, which are determination and differentiation class myogenic regulatory factors, respectively. Functional assays showed that ectopic p27 expression can powerfully enhance the efficiency of MyoD-initiated muscle differentiation in cell culture. When considered together with the myotomal expression patterns of p18, p21, and p57, these results suggest a model in which p27 acts as a "trigger" CDI while myoblasts are exiting the cell cycle and initiating differentiation. At later times, when p27 protein has been down-regulated, it is proposed that accumulation of p18, p21, and p57 maintain the differentiated myocytes in a postmitotic state.
To the Editor:-I read with interest the article "Randomized Study Comparing the 'Sniffing Positio... more To the Editor:-I read with interest the article "Randomized Study Comparing the 'Sniffing Position' with Simple Head Extension for Laryngoscopic View in Elective Surgery Patients" by Adnet et al. 1 The authors challenged the sniffing position as the standard head position for laryngoscopic intubation, and they concluded "routine use of the sniffing position appears to provide no significant advantage over simple head extension for tracheal intubation." I read through the article carefully and found some questions about their study. First, the degree of glottic exposure depends on the effort during the laryngoscopy. One proposed advantage of the sniffing position is that it reduces the effort required to expose the glottis. 2 However, the authors simply compared the glottic exposure between the sniffing position and the head extension position, without noting the effort during the laryngoscopy. Second, the total number of patients with each IDS score in figure 2 is not equal to the number the authors reported. The sum of the patients in the sniffing position shown on each bar is 228 (128 ϩ 36 ϩ 34 ϩ 10 ϩ 14 ϩ 1 ϩ 3 ϩ 2 ϭ 228), and the sum of the patients in the head extension group is also 228 (111 ϩ 62 ϩ 30 ϩ 13 ϩ 4 ϩ 2 ϩ 2 ϩ 1 ϩ 1 ϩ 1 ϩ 1 ϭ 228). However, the authors claimed that 225 patients were included in the sniffing position group and 231 in the simple head extension group. This mistake should be clarified. Nevertheless, the other conclusion they achieved is thought-provoking: "The sniffing position appears to be advantageous for obese and head extensionlimited patients." Is more laryngoscopy effort required to expose the glottis in these two kinds of patients? The advantage of the sniffing position might lie beneath that question. Based on these considerations, I am not convinced that the findings of Dr. Adnet et al. could challenge the clinical usefulness of the sniffing position. I believe that the sniffing position is still the optimal position in reducing the effort to expose the glottis during laryngoscopy.
Study Objective: To test the hypothesis that morbid obesity implies increased dz;ffulty of liver ... more Study Objective: To test the hypothesis that morbid obesity implies increased dz;ffulty of liver transplantation and increased risk of adverse outcome. Design: Retrospective review of medical records of 40 morbidly obese patients using a control cohort of patients transplanted just before and after the obese patients. Setting: University medical center. Patients: All morbidly obese patients who underwent liver transplantation over a 5% month period were included. Forty adult patients met criterion for morbid obesity with body mass index greater than 30 kg/m2. Records for 61 time-matched controls were reviewed. Measurements and Main Results: Demographic, intraoperative, and postoperative data were collected including preoperative diagnoses, laboratory and pulmonary function tests, intraoperative transfusion requirements and length of surgey, postoperative complications, and survival. Data were analyzed using Student's t-tests, and Chi-square analyses as appropriate, with significance considered a p-value less than 0.05. Obese patients were more hypoxemic than controls prior to surgery (PaO, 82.9 f 3.5 vs. 93.0 + 3.0 mmHg), were more likely to be diabetic, and had higher creatinine levels (3.0 * 0.6 vs. 1.7 + 0.2 mg/dlJ. Despite this evidence of multi-organ dysfunction, intraoperative and postoperative pulmonary and cardiac complications did not diffu between groups. Though more obese patients had prior cholecystectomy, length of surgery and intraoperative transfusion requirements were not different between groups. Obese patients did not have an increased incidence of reoperation for wound problems, and lengths of intensive care unit and hospital stays did not differ between groups. Graft and patient survival were similar in obese and nonobese liver transplant recipients. Conclusion: Morbid obesity alone does not predispose to increased complications or decreased survival afier liver transplantation.
Tumor necrosis factor stimulates DNA synthesis of mouse hepatocytes in primary culture and is sup... more Tumor necrosis factor stimulates DNA synthesis of mouse hepatocytes in primary culture and is suppressed by transforming growth factor beta and interleukin 6.
Inflammation is a normal, robust physiological process. It can also be viewed as a complex system... more Inflammation is a normal, robust physiological process. It can also be viewed as a complex system that senses and resolves homeostatic perturbations initiated from within the body (for example, in autoimmune disease) or from the outside (for example, in infections). Virtually all acute and chronic diseases are either driven or modulated by inflammation. The complex interplay between beneficial and harmful arms of the inflammatory response may underlie the lack of fully effective therapies for many diseases. Mathematical modeling is emerging as a frontline tool for understanding the complexity of the inflammatory response. A series of articles in this issue highlights various modeling approaches to inflammation in the larger context of health and disease, from intracellular signaling to whole-animal physiology. Here we discuss the state of this emerging field. We note several common features of inflammation models, as well as challenges and prospects for future studies.
Marie Csete of Emory University, Department of Anesthesiology presented a lecture on March 18, 20... more Marie Csete of Emory University, Department of Anesthesiology presented a lecture on March 18, 2003 at 11:00 am in the Suddath Seminar Room, IBB Building, Georgia Tech Campus.
Heat shock proteins (HSP) are important in neuroprotection after a variety of stresses or injurie... more Heat shock proteins (HSP) are important in neuroprotection after a variety of stresses or injuries. Both heat shock proteins and endothelin are upregulated after peripheral nerve injury, but HSP regulation after injury has not been systematically studied in peripheral nerve. The purpose of this study was to examine the regulation of small and large heat shock proteins after injury to rat sciatic nerve. Secondly, using a parallel tissue culture model for the sciatic nerve (PC12 cells), we examined potential regulation of heat shock proteins by endothelin. Western analysis of constricted, mobilized or unperturbed nerve was used to examine HSP abundance after injury. Semiquantitative PCR was used to examine heat shock message levels after nerve injury in the dorsal root ganglia. Cultured undifferentiated and differentiated PC12 cells were treated with endothelin, then western analysis of cytosol-and membrane-enriched fractions of these cells was used to examine heat shock protein regulation after endothelin treatment. Heat shock proteins are expressed at very low levels in unperturbed sciatic nerve. Constriction injury of the nerve results in increased expression of small and large heat shock proteins, but no upregulation of HSP message in corresponding dorsal root ganglia. Endothelin treatment of PC12 does not cause upregulation of heat shock proteins. Together these data show that a broad range of HSP is involved in endogenous response to peripheral nerve injury and deserve further study as potential neuroprotectants. Regulation of heat shock proteins after nerve injury is not likely due to endothelin signaling.
We examined data and patterns in clinical islet transplant studies registered on ClinicalTrials.g... more We examined data and patterns in clinical islet transplant studies registered on ClinicalTrials.gov (CTgov) for treatment of type 1 diabetes (T1D), with a goal of extracting insights to apply in the design of a pluripotent stem cell-derived islet therapy. Clinical islet transplantation, as a cell therapy (rather than solid organ transplant) is a unique precedent for stem cell-based islet therapies. Registration activity shows that the field is not growing significantly, and newer registrations suggest that the reasons for stagnation include need for a more optimal site of infusion/transplantation, and especially a need for better immune protective strategies to advance a more effective and durable therapy for T1D.
Vertebrate skeletal muscle development is characterized by tight coupling of muscle differentiati... more Vertebrate skeletal muscle development is characterized by tight coupling of muscle differentiation with cell cycle arrest in G1/G0. Key regulators of G1 progression are the G1 cyclin-dependent kinases, their positive regulators, the G1 cyclins, and their negative regulators, the cyclin-dependent kinase inhibitors (CDIs). Here we show that p27Kip1 protein, a G1 CDI, is expressed in a prominent but transient wave in the developing myotomes of the mouse embryo. We relate its expression to expression of MyoD and myogenin proteins, which are determination and differentiation class myogenic regulatory factors, respectively. Functional assays showed that ectopic p27 expression can powerfully enhance the efficiency of MyoD-initiated muscle differentiation in cell culture. When considered together with the myotomal expression patterns of p18, p21, and p57, these results suggest a model in which p27 acts as a "trigger" CDI while myoblasts are exiting the cell cycle and initiating differentiation. At later times, when p27 protein has been down-regulated, it is proposed that accumulation of p18, p21, and p57 maintain the differentiated myocytes in a postmitotic state.
To the Editor:-I read with interest the article "Randomized Study Comparing the 'Sniffing Positio... more To the Editor:-I read with interest the article "Randomized Study Comparing the 'Sniffing Position' with Simple Head Extension for Laryngoscopic View in Elective Surgery Patients" by Adnet et al. 1 The authors challenged the sniffing position as the standard head position for laryngoscopic intubation, and they concluded "routine use of the sniffing position appears to provide no significant advantage over simple head extension for tracheal intubation." I read through the article carefully and found some questions about their study. First, the degree of glottic exposure depends on the effort during the laryngoscopy. One proposed advantage of the sniffing position is that it reduces the effort required to expose the glottis. 2 However, the authors simply compared the glottic exposure between the sniffing position and the head extension position, without noting the effort during the laryngoscopy. Second, the total number of patients with each IDS score in figure 2 is not equal to the number the authors reported. The sum of the patients in the sniffing position shown on each bar is 228 (128 ϩ 36 ϩ 34 ϩ 10 ϩ 14 ϩ 1 ϩ 3 ϩ 2 ϭ 228), and the sum of the patients in the head extension group is also 228 (111 ϩ 62 ϩ 30 ϩ 13 ϩ 4 ϩ 2 ϩ 2 ϩ 1 ϩ 1 ϩ 1 ϩ 1 ϭ 228). However, the authors claimed that 225 patients were included in the sniffing position group and 231 in the simple head extension group. This mistake should be clarified. Nevertheless, the other conclusion they achieved is thought-provoking: "The sniffing position appears to be advantageous for obese and head extensionlimited patients." Is more laryngoscopy effort required to expose the glottis in these two kinds of patients? The advantage of the sniffing position might lie beneath that question. Based on these considerations, I am not convinced that the findings of Dr. Adnet et al. could challenge the clinical usefulness of the sniffing position. I believe that the sniffing position is still the optimal position in reducing the effort to expose the glottis during laryngoscopy.
Uploads
Papers by Marie Csete