Journal of Surgical Research

Caveolin-1 Regulating the Invasion and Expression of Matrix Metalloproteinase (MMPs) in Pancreatic Carcinoma Cells

Fei Han, Hong-Guang Zhu — 2009-05-04

The gelatinases B (MMP9) and A (MMP2) are two members of the matrix metalloproteinase (MMPs) family that are expressed in human cancer, and play a critical role in tumor cell invasion and metastasis. Caveolin-1 (Cav1) has recently been identified as a tumor metastasis modifier gene. However, the effect and mechanism of Cav1 in pancreatic carcinoma cell invasion remain unknown. In this study, we investigated the expression of Cav1, MMP2, and MMP9 in several different pancreatic carcinoma cell lines. We transfected pcDNA3.0-Cav1 plasmid and Cav1 siRNA into SW1990 and Bxpc3 cells, respectively. Using cell invasion assay, we found that overexpression of Cav1 inhibited cell invasion, whereas the knockdown of Cav1 in Bxpc3 cells promoted cell invasion. Moreover, to explore the mechanisms underlying these observations, we further investigated the expression of MMP2, MMP9, phospho-Akt, and phospho-Erk by Western blot, and the activities of MMP2 and MMP9 by gelatin zymography. The results indicated that Cav1 gene could inhibit pancreatic carcinoma cell invasion, at least in part, probably through Erk-MMP signal pathway, suggesting that the endogenous expression or re-expression of Cav1 might help therapeutically reduce their invasive potential in pancreatic carcinoma cells.

Hydrogen Sulfide Protects Against Ischemia-Reperfusion Injury in an In Vitro Model of Cutaneous Tissue Transplantation1

2009-06-08

Background: Ischemia-reperfusion injury (IRI) is a source of morbidity and mortality in many clinical scenarios, and has as one of its many consequences the induction of cellular apoptosis. Hydrogen sulfide (H2S) may decrease cellular metabolism in a reversible, nontoxic manner. An in vitro model of cutaneous tissue transplantation was developed to assess whether H2S could ameliorate cellular injury caused by IRI.Methods: Human umbilical vein endothelial cells (HUVECs) were treated with media containing NaHS (0, 10 μM, 100 μM, or 1 mM) and exposed to normoxia (21% oxygen), hypoxia (1%), or anoxia (0%). Cells were then returned to normoxia, and apoptosis was quantified using a terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Fibroblasts (3T3s) were treated with H2S and exposed to anoxia in a similar fashion.Results: Treatment with H2S resulted in a significant decrease in apoptosis in HUVECs and 3T3s subjected to IRI. Toxicity of H2S was not observed, although the protective effect was less evident at higher doses.Conclusion: This is the first study to examine H2S and the cellular components of cutaneous flaps in the setting of IRI. Our results demonstrate that H2S significantly decreases apoptosis in vitro in the setting of IRI. These data suggest H2S may mitigate IRI in vivo, and, therefore, has potential as a therapy for improving tissue survivability in clinical scenarios.

Physical Examination is a Poor Screening Test for Abdominal-Pelvic Injury in Adult Blunt Trauma Patients

2009-06-08

Background: To determine if physical examination can reliably detect or exclude abdominal or pelvic injury in adult trauma activation patients.Methods: Trauma registry and medical record data were retrospectively reviewed for all adult blunt trauma patients with Glasgow coma scale score>8, from 6/30/05 to 12/31/06. Attending surgeons' dictated admission history and physical examination reports were individually reviewed. Patients' subjective reports of abdominal pain were recorded as present or absent. Exam findings of the lower ribs, abdomen, and pelvis were each separately recorded as positive or negative, and were compared with findings on a subsequent objective evaluation of the abdomen (OEA). “Clinically significant” injuries were defined as those that would change patient management.Results: One thousand six hundred sixty-three patients were studied. Of patients with a negative abdominal exam, 10% had a positive OEA. When abdominal pain was absent, and exam of the lower ribs, abdomen, and pelvis was normal, OEA was positive in 7.6%, and 5.7% had a clinically significant injury. While a positive abdominal exam was predictive of a positive OEA (P<0.01), a negative exam, even when broadened (pain, lower ribs, abdomen, pelvis) did not exclude significant injuries.Conclusion: Ten percent of trauma activation patients with a negative abdominal exam have occult abdominal/pelvic injuries. Even when exam of the lower ribs, abdomen, and pelvis are all negative and abdominal pain is absent, 5.7% have occult injuries that would change management. OEA should be used liberally for adult blunt trauma activation patients regardless of physical exam findings, to avoid missing clinically significant injuries.

Teaching Breaking Bad News Using Mixed Reality Simulation

2009-05-21

Background: Our novel teaching approach involved having students actively participate in an unsuccessful resuscitation of a high fidelity human patient simulator with a gun shot wound to the chest, followed immediately by breaking bad news (BBN) to a standardized patient wife (SPW) portrayed by an actress.Methods: Brief education interventions to include viewing a brief video on the SPIKES protocol on how to break bad news, a didactic lecture plus a demonstration, or both, was compared to no pretraining by dividing 553 students into four groups prior to their BBN to the SPW. The students then self-assessed their abilities, and were also evaluated by the SPW on 21 items related to appearance, communication skills, and emotional affect. All received cross-over training.Results: Groups were equal in prior training (2h)and belief that this was an important skill to be learned. Students rated the experience highly, and demonstrated marked improvement of self-assessed skills over baseline, which was maintained for the duration of the 12-wk clerkship. Additionally, students who received any of the above training prior to BBN were rated superior to those who had no training on several communication skills, and the observation of the video seemed to offer the most efficient way of teaching this skill in a time delimited curriculum.Conclusion: This novel approach was well received and resulted in improvement over baseline. Lessons learned from this study have enhanced our curricular approach to this vital component of medical education.

A Different View of Lactate in Trauma Patients: Protecting the Injured Brain

2009-05-15

Background: The relationship between lactate and head injury is controversial. We sought to determine the relationship between initial serum lactate, severity of head injury, and outcome. We hypothesized that lactate is elevated in head injured patients, and that initial serum lactate increases as the severity of head injury increases. Furthermore, lactate may be neuroprotective and improve neurologic outcomes.Materials and Methods: We identified normotensive adult patients over a 6-y period at our university-based urban trauma center with isolated blunt head injury. We performed univariate and multivariate analysis to examine the relationship between lactate and Glasgow coma scale (GCS). The correlation of admission lactate with survival and neurologic function was also examined.Results: There were 555 patients who met study criteria. While controlling for injury severity score and age, increased lactate was associated with more severe head injury (P < 0.0001). The admission lactate was 2.2 ± 0.07, 3.7 ± 0.7, and 4.7 ± 0.8 mmol/L in patients with mild, moderate, and severe head injury respectively (P < 0.01). Patients with moderate or severe head injury and an admission lactate > 5 were more likely to have a normal mental status on discharge (P < 0.0001).Conclusions: In normotensive isolated head injured patients, there was an increase in serum lactate as head injuries became more severe. Since lactate is a readily available fuel source of the injured brain, this may be a mechanism by which brain function is preserved in trauma patients. Elevations in lactate due to anaerobic metabolism in trauma patients may have beneficial effects by protecting the brain during injury.

Identification of a Novel Potential Biomarker in a Model of Hemorrhagic Shock and Valproic Acid Treatment1

2009-05-15

Background: The initial management of a poly-trauma patient requires evaluation for potential hemorrhage and ongoing monitoring to assess the efficacy of treatment and avoid complications related to massive blood loss. Certain serum protein levels may be altered in response to hemorrhagic shock, and may serve as useful biomarkers to guide diagnosis, prognosis, and therapeutics in traumatic hemorrhagic shock (HS). Treatment with valproic acid (VPA) has been shown to up-regulate various survival pathways and improve outcome. Here we determine whether these changes would result in altered serum biomarkers.Methods: Wistar-Kyoto rats underwent hemorrhagic shock (60% blood loss) followed by treatment with or without VPA (300 mg/kg). Using surface enhanced laser desorption-time of flight mass spectrometry (SELDI or SELDI-TOF MS) technology, we screened serum samples obtained from five rats at different time points (baseline, post-hemorrhagic shock, and post-VPA treatment) in a lethal model of hemorrhagic shock (HS). Additionally, we used isobaric tag labeling for relative quantitation (iTRAQ) to identify potential biomarkers in the serum. Western blots were performed to validate iTRAQ-identified biomarker from independent serum samples, and to analyze protein biomarker levels in the intestine during hemorrhagic shock and treatment.Results: HS and treatment with VPA affected serum levels of many proteins. One such protein with a mass spectrum around 22.7 kDa was detected in all five rats. The same serum samples subjected to iTRAQ resulted in our identification of claudin-3, a 23 kDa tight junction protein. HS elevated serum claudin-3 protein levels, which was reversed by VPA treatment in a pattern similar to the SELDI-TOF MS studies. Further validation with independent serum and intestine samples from individual rats by Western blots confirmed that HS increased the protein level of claudin-3 in serum and decreased its level in the intestine. Treatment with VPA reversed the hemorrhagic shock-induced alteration in claudin-3 to sham levels.Conclusions: HS causes an acute rise in serum claudin-3 protein levels and a concurrent decrease in intestinal claudin-3 protein expression. VPA treatment attenuates these alterations and stabilizes intestinal claudin-3 levels. Our results demonstrate for the first time that claudin-3 is a potential biomarker in HS and treatment.

The Johns Hopkins Surgery ABSITE Review Manual

Mackenzie R. Cook, Susan C. Pitt — 2009-02-26

As a yearly exam for general surgery house staff, the American Board of Surgery In-Training Exam (ABSITE) has generated a review book industry that provides a broad and deep range of options for the surgical resident. The Johns Hopkins Surgery ABSITE Review Manual, a production of the Halsted residents, stands out from the crowd as a well-written, effective, easy-to-use, and efficient review for the junior and senior ABSITE exams. The manual could also be utilized during study for the American Board of Surgery (ABS) qualifying or recertification exam.

Commentary

Alan Dardik — 2009-05-18

Over the past decades, vascular surgeons have observed many gender specific demographic trends in patients presenting with abdominal aortic aneurysms (AAA). For example, patients with AAA are more likely to be male, and these aneurysms are more likely to be transmitted to sons rather than daughters. Women have increased mortality rates after open AAA repair compared with men . Women presenting with aneurysms are less likely to be candidates for endovascular repair, not only due to their smaller iliac arteries, making it less likely to deliver large-profile devices, but women also present with wider and more tortuous infrarenal necks, making it less likely to find an appropriate attachment site .

Pediatric FAST and Elevated Liver Transaminases: An Effective Screening Tool in Blunt Abdominal Trauma

Lee David Faucher — 2009-05-15

I would like to thank the authors for advancing a well-known technique of abdominal ultrasound in the evaluation of pediatric blunt abdominal trauma. It was not long ago that Focused Assessment with Sonography for Trauma (FAST) was not recommended in pediatric trauma as a screening tool to predict injury. There are now other studies that have found FAST to be a useful adjunct in the evaluation of the pediatric blunt trauma patient . This is the first study that has included laboratory blood analysis in conjunction with abdominal ultrasound to predict injury, all to avoid the known complications of radiation exposure caused by computed tomography .

The Dying Field of General Surgery: When Do We Intervene? Why Residents Choose to Specialize in Fields Outside Surgery

Steven B. Goldin — 2009-05-25

In the manuscript, The Dying Field of General Surgery: When Do We Intervene? the authors recognize that fewer surgical residents are pursuing general surgery careers . The profession of general surgery faces ominous problems including a deficit of practicing general surgeons with a projected workload increase . Fewer medical students choose careers in general surgery for a multitude of reasons, with the two most important being concern over quality of life and their desire for a controllable lifestyle . Similarly, as discussed in the manuscript, a growing number of general surgery residents are specializing after training. To understand the reasons why general surgical residents specialize, several aspects of current training and surgical culture must be examined, which include the residents' feelings about the adequacy of their general surgery training, their feelings about their need to for more advanced certification, and their feelings about the overall field of general surgery, which continues shrink due to an increasing number of specialized fellowships in areas that were once considered the domain of the general surgeon.

Prospective Randomized Study for Comparison of Open Surgery with Laparoscopic-Assisted Placement of Tenckhoff Peritoneal Dialysis Catheter—A Single Center Experience and Literature Review

Shyh-Chuan Jwo, Kuo-Su Chen, Chin-Chan Lee, Huang-Yang Chen — 2008-10-09

Background: The ideal method for catheter placement in patients undergoing peritoneal dialysis remains debatable. This prospective study intends to clarify whether laparoscopic assisted percutaneous puncture is superior to open surgery.Materials and Methods: From 2002 to 2006, 77 patients receiving first catheter placement were enrolled and randomized to either an open group of 40 patients or a laparoscopic group of 37 patients. Patient characteristics, operation-related data, procedural complications, and clinical outcome were compared by using the statistical software SPSS ver. 11.5 (SPSS, Chicago, IL).Results: Laparoscopy had a longer operative time (68.32 ± 31.90 versus 46.68 ± 15.99 min; P < 0.001), shorter wound length (1.69 ± 0.46 versus 2.34 ± 0.84 cm; P < 0.001), and higher costs (P < 0.001) compared with open surgery. Laparoscopy tended to have a higher incidence of pericannular bleeding (21.6% versus 7.5%) and a lower rate of early catheter migration (2.7% versus 15.0%), but its early/late/overall complication rate did not statistically differ. No surgical mortality occurred. Rate and cause of overall mortality or catheter dropout did not statistically differ. Catheter longevity was equivalent in both groups.Conclusions: Laparoscopic assisted percutaneous puncture exhibited no superiority to open surgery. As a matter of fact, open surgery's shorter operative time and reduced equipment requirement can increase cost-effectiveness. Therefore, conventional open surgery is recommended for most patients with primary catheter placement.

Curcumin Attenuates Oxidative Stress and Inflammatory Response in the Early Phase after Partial Hepatectomy with Simultaneous Intraabdominal Infection in Rats

2009-01-05

Background: Curcumin is a nontoxic, hepatoprotective antioxidant. It has been shown to efficiently scavenge oxygen free radicals, increase intracellular glutathione concentrations, and prevent lipid peroxidation in rat hepatocytes. Moreover, it has strong anti-inflammatory effects. In the present study we assessed its effect in a model of liver regeneration impaired by bacterial infections.Material and Methods: Male Sprague-Dawley rats underwent sham operation, cecal ligation and puncture (CLP), synchronous partial hepatectomy (PH), and CLP or synchronous PH+CLP with perioperative application of curcumin (100 mg per kg bodyweight per d) 48 h before surgery. Rats were sacrificed 24 h after surgery. Liver function was analyzed by measuring the serum albumin, serum bilirubin, and bile production. The local inflammatory response in the liver tissue was evaluated by quantification of TNF-α, IL-6 mRNA, and quantification of IL-1ß by ELISA. In addition, hepatic concentrations of reduced glutathione (GSH) and the oxidized disulfide dimer of glutathione (GSSG) were measured for determination of the redox state.Results: After simultaneous PH+CLP curcumin significantly reduced the expression of TNF- α and IL-6 mRNA in the liver tissue. The IL-1β concentration in the liver was also slightly, but not significantly, lower in the curcumin group. A severe depletion of hepatic glutathione was found in the PH+CLP group. This was reversed by curcumin application, after which the GSH to GSSG ratio increased markedly. The hepatocellular damage, measured by ALT liberation, was significantly lower in the curcumin treated group. The relative liver weight in the curcumin group was significantly higher 24 h after PH+CLP. However, hepatocellular proliferation parameters were not significantly improved by antioxidative treatment with curcumin. Only the Ki-67 index was slightly higher in the curcumin treated PH+CLP group (14 ± 3%) than in the untreated PH+CLP group (7% ± 3%). The hepatocyte density was significantly lower in the curcumin group than in the corresponding untreated group.Conclusion: In the present model, curcumin revealed significant hepatoprotective effects with stabilization of redox state, reduced liberation of liver enzymes, and attenuated expression of pro-inflammatory cytokines. However, the hepatocellular proliferation was not significantly influenced.

The Effects of Different Nutritional Measurements on Delayed Wound Healing After Hip Fracture in the Elderly

2008-10-17

Background: It has been well recognized that malnutrition causes wounds to heal inadequately and incompletely. Malnutrition is often observed in the elderly, and it appears to be more severe in patients with hip fracture than in the general aging population. Few prospective studies give a detailed account of the identification and classification of nutritional status in the elderly. The objective of this study was to evaluate the effects of different nutritional measurements on wound healing status after hip fracture in the elderly.Methods: From September 2002 to December 2007, 207 hip fracture patients older than 60 y treated surgically were reviewed for preoperative nutritional status. There were 81 males and 126 females with an average age of 75.93 y (62–91 y); 131 cases with femoral neck fractures, 76 cases with intertrochanteric fractures. Parameters indicative of nutritional status (serum albumin, serum transferrin, serum pre-albumin, and total lymphocyte count levels) at the time of admission were assessed, along with anthropometric measurements, Rainey MacDonald nutritional index, and MNA tool. Suture removal was performed on postoperative day 14.Results: Delayed wound healing complicated 46 (22.2%) of the 207 cases. The preoperative serum transferring total lymphocyte count levels, MNA total score, and Rainey MacDonald nutritional index were significantly lower for patients who subsequently had delayed wound healing. When all variables were subjected to multivariate analysis, only total lymphocyte count levels and MNA total score showed significant value in predicting which patients would have delayed wound healing. Through prophylactic antibiotics and adherence to strict aseptic precautions, on follow-up, wound healing was normal in all patients.Conclusions: Patients at risk for delayed wound healing problems after hip fracture can be identified using relatively inexpensive laboratory test such as TLC and MNA tool. The clinician must be aware of the risk values of both measurements. We believe this information is particularly important before planning procedures of hip fractures in the elderly.

Ischemia-Reperfusion Injury in Skeletal Muscle: Comparison of the Effects of Subanesthetic Doses of Ketamine, Propofol, and Etomidate

Yusuf Ergün, Hafize Öksüz, Yalcin Atli, Metin Kılınç, Sacide Darendeli — 2008-08-28

Background: Interest in the effects of anesthetics in skeletal ischemia-reperfusion injury (IRI) has recently emerged. Thus, the objective was to compare the effects of subanesthetic doses of ketamine, propofol, and etomidate in a skeletal IRI model.Methods: IRI was applied to rats by tourniquet method. Under thiopental anesthesia, five experimental groups were established as follows: (1) sham-control, (2) IRI, (3) IRI+Ketamine, (4) IRI+Propofol, and (5) IRI+Etomidate. Malondialdehyde, superoxide dismutase, catalase, and glutathione peroxidase were measured in skeletal muscle via a spectrophotometer. Zinc, iron, copper, and selenium were evaluated by atomic absorption spectrophotometer.Results: While the values of malondialdehyde and glutathione peroxidase were higher and lower, respectively, those of superoxide dismutase and catalase were identical in IRI group in comparison with sham-control. Zinc displayed a decrease in IRI group; however, no differences in iron and copper levels were determined. In rats treated with subanesthetic doses of ketamine, elevated malondialdehyde levels in IRI group were reversed to control levels by each dose. While each dose of ketamine decreased superoxide dismutase activities in comparison with IRI group, a reduction in catalase activity was only seen in 3mg/kg ketamine-treated rats. The attenuated glutathione peroxidase activity seen in IRI was greatly reversed by ketamine administration in all doses. No differences in zinc, copper, and iron levels were detected between IRI and ketamine-treated groups. Similar results were obtained either by the administration of propofol or etomidate.Conclusions: Subanesthetic doses of ketamine, propofol and etomidate displayed beneficial effects in IRI.

Pretreatment with Dexmedetomidine or Thiopental Decreases Myoclonus after Etomidate: A Randomized, Double-Blind Controlled Trial

2009-08-20

Background: Myoclonic movements are common problems during induction of anesthesia with etomidate. The aim of this study was to compare the effect of pretreatment with dexmedetomidine (0.5 μg/kg) and thiopental (1 mg/kg) on the incidence of etomidate- induced myoclonus and postoperative pain.Materials and Methods: A prospective double-blind study was conducted at a university hospital. Ninety patients (ASA physical status I-II) were randomly assigned to one of three groups: patients were pretreated with either dexmedetomidine (0.5 μg/kg), thiopental (1mg/kg), or saline before induction of anesthesia with etomidate. One minute after the injection of study drugs, etomidate, 0.3mg/kg was given. Myoclonus was assessed on a scale of 0 to 3. Recovery time, postoperative pain score, and hemodynamic variables were recorded during the intraoperative and postoperative period. Headache, nausea, vomiting, and coughing were noted during the study.Results: The incidence and the intensity of myoclonus was significantly lower in the dexmedetomidine and thiopental groups (34%, 36%) than in the control group (64%) (P<0.05). The postoperative pain score at 30min in the thiopental group was significantly higher than in the dexmedetomidine and control groups (63%) (P<0.05).Conclusions: We concluded that pretreatment with dexmedetomidine or thiopental is effective in reducing the incidence and severity of etomidate-induced myoclonic muscle movements and pretreatment with thiopental increases the postoperative pain.

Prognostic Criteria for Squamous Cell Cancer of the Skin

2009-01-05

Background: Non-well-differentiated cutaneous squamous cell carcinomas may display a more aggressive behavior. It is important to better define prognostic criteria for these tumors.Methods: This was a retrospective case-control analysis of a squamous cell carcinoma database. Patients with non-well-differentiated and well-differentiated tumors were matched based on site of tumor, age, and immunocompromised status. Comparisons included demographics, histology, immunohistochemical protein expressions (Ki-67, p53, E-cadherin, cyclin D1), and clinical outcomes.Results: Demographic features were similar between cases (n = 30) and controls (n = 30). Non-well-differentiated tumors were larger (1.8 cm versus 1.3 cm, P = 0.08), deeper (0.81 cm versus 0.32 cm, P < 0.0001), and had greater recurrence (P = 0.003). Non-well-differentiated tumors showed increased proliferation rate, Ki-67 index (77% versus 61%, P = 0.001); no significant difference in activity of p53, E-cadherin, and cyclin D1 between the two groups.Conclusions: Tumor differentiation and depth are important pathologic and prognostic criteria for cutaneous squamous cell carcinoma. Immunohistochemistry helps describe patterns of biomarker protein expression and may exemplify aggressive subtypes.

The Role of VEGF Pathways in Human Physiologic and Pathologic Angiogenesis

2009-01-12

Background: In preclinical models, VEGF is a potent stimulant of both physiologic and pathologic angiogenesis. Conversely, anti-VEGF regimens have successfully inhibited angiogenesis both in vitro and in vivo. We hypothesized that VEGF would stimulate both physiologic and pathologic angiogenesis in a human-based fibrin-thrombin clot angiogenesis assay. We further speculated that anti-VEGF regimens would inhibit angiogenesis in this assay.Methods: To test these hypotheses, discs of human placental veins (physiologic model) and fragments of human tumors (pathologic model) were embedded in fibrin-thrombin clots and treated with either VEGF-A165 (VEGF) or anti-VEGF pathway reagents including bevacizumab, IMC-18F1, IMC-1121, and PTK787 (n = 30 wells per treatment group, multiple concentrations tested in each specimen). Angiogenic responses were assessed visually using a previously validated grading scheme. The percent of tissue explants that developed angiogenic invasion into the clot (%I) as well as the extent of angiogenic growth (AI) via a semi-quantitative scale were assessed at set intervals.Results: VEGF failed to stimulate angiogenesis in both the physiologic and the pathologic model. While anti-VEGF reagents that targeted only one element of the VEGF pathway failed to consistently inhibit angiogenesis, PTK787, a receptor tyrosine kinase inhibitor that targets multiple VEGF and non-VEGF receptors, profoundly inhibited both physiologic and pathologic angiogenesis.Conclusion: These results suggest that VEGF-related pathways may not be solely responsible for stimulating angiogenesis in humans. Targeting the VEGF pathway in combination with elements of other growth factor pathways may provide a more effective means of inhibiting angiogenesis than targeting VEGF alone.

Mammography as a Screening Tool for Diabetes

Paul S. Dale, Christopher R. Mascarenhas, Michael Richards, Gavin Mackie — 2008-12-17

Background: This large retrospective study investigates the relationship between breast arterial calcifications (BAC) identified on screening mammography and the presence of DM, thereby evaluating the utility of screening mammography as an additional screening tool for diabetes.Materials and Methods: The screening mammograms of 1000 women were prospectively evaluated for BAC; women with a prior history of DM or CAD were excluded. This screening group was compared with all diabetic women who had undergone routine mammographic screening at our institution. The relationship between BAC and DM was statistically evaluated.Results: Of the 1000 women prospectively evaluated, we identified 819 women without a history of either DM or CAD. Of these 819 women, mammographic BAC was identified in 86 for a baseline incidence of BAC in our screening population of 10%. We identified 790 diabetic women who had undergone screening mammograms at our institution, and BAC was identified in 288 (36.45%). The incidence of vascular calcifications was significantly higher in the DM group (P < 0.001) than in the screening group, irrespective of age. Stratifying by age group, we identified a significant relationship between BAC and DM (CMH test P < 0.001). The estimated odds ratio of having diabetes if BAC is present is compared with BAC being absent is 4.5 (95% confidence interval (3.2, 6.1).Conclusions: BAC identified on routine screening mammography can identify a group of women at high risk for diabetes. Prospective studies are currently underway at our institution to confirm the utility of screening mammography as a screening tool for diabetes.

Radiofrequency Ablation of Liver Tumors: A Novel Needle Perfusion Technique Enhances Efficiency

Paolo Abitabile, Christoph A. Maurer — 2008-10-01

Objective: We hypothesize that perfusion of an expandable radiofrequency ablation (RFA) needle with saline solution might help prevent charring and increase efficiency.Summary Background Data: RFA has become an important adjunct to modern liver surgery. However, ablation is time-consuming and hazardous due to charring around the radiofrequency electrodes.Methods: From June 2000 to November 2004, 159 liver tumors with a median diameter of 2.0cm were treated with RFA, 54 tumors of them according to the manufacturer's standard protocol and 105 tumors according to the novel perfusion protocol. No randomization was applied. All patients were followed up with contrast enhanced computed tomography (CT) at regular intervals. Local recurrence was defined as radiologic and/or histologic evidence of viable tumor within or at the ablated liver area.Results: Both study groups were comparable with regard to tumor characteristics, procedure related complications, and median times of follow-up (27 mo in the standard group versus 23 mo in the perfusion group). The median RFA time was significantly reduced from 18.9 min in the standard group to 8.0 min in the perfusion group. The rates of incomplete ablations were comparable in both groups (3.7% versus 2.8%). The rate of local recurrences at the RFA site was 6.9% overall, 11.1% in the standard group, and 4.8% in the perfusion group. No tumor seeding along the puncture channel was observed.Conclusions: The perfusion of an expandable RFA needle with saline solution significantly accelerates the ablation procedure of liver tumors without increase of complications and without compromising the oncosurgical result.

LCSGJ-T Classification, 6th or 5th Edition TNM Staging Did Not Independently Predict the Long-Term Prognosis of HBV-Related Hepatocellular Carcinoma After Radical Hepatectomy

Li Zhou, Jing-An Rui, Shao-Bin Wang, Shu-Guang Chen, Qiang Qu — 2008-10-06

Background: The 6th edition tumor-node-metastasis (TNM) staging (TNM-6) for hepatocellular carcinoma (HCC) was recommended. Besides, Liver Cancer Study Group of Japan (LCSGJ)-T classification has been recently proposed. However, these newly established staging systems should be further verified in different subgroups of HCC patients. The current study mainly aimed to validate the predictive power of these novel criteria in a cohort of patients with hepatitis B virus-related HCC after radical hepatectomy. As a control, the 5th edition TNM staging (TNM-5) was also evaluated.Methods and Materials: Clinicopathological and follow-up data of consecutive 142 patients with HBV-related HCC undergoing radical hepatectomy were reviewed. The impact of variables on prognosis was determined by uni- and multivariate analyses.Results: By univariate analysis, LCSGJ-T classification, TNM-6, and TNM-5 were almost significantly prognostic, except for TNM-5 for disease-free survival. Meanwhile, tumor size≥5cm, α-fetoprotein>400 ng/mL , high Edmondson-Steiner grade, presence of microvascular invasion, portal vein tumor thrombosis, satellite nodule, and resection margin≤1cm were also associated with decreased overall or disease-free survival. Multivariate analysis, including aforementioned factors, suggested that Edmondson-Steiner grade was the sole independent prognosticator for both overall and disease-free survival, when LCSGJ-T classification, TNM-6, and TNM-5 were entered, respectively. However, all 3 staging systems lost their predictive potentials in multivariate analysis.Conclusions: LCSGJ-T classification, TNM-6, and TNM-5 were not revealed to be independently prognostic in patients with HBV-related HCC after radical hepatectomy. Therefore, these staging criteria, especially the newly developed ones, call for more support in many subsets of HCC patients.

New Concepts for Basal Cell Carcinoma. Demographic, Clinical, Histological Risk Factors, and Biomarkers. A Systematic Review of Evidence Regarding Risk for Tumor Development, Susceptibility for Second Primary and Recurrence

2008-12-15

Basal cell carcinoma (BCC) is the commonest cancer in Caucasians and its incidence is increasing. Whilst ultraviolet radiation (UVR) is recognized as the main etiological factor, the relationship between exposure and host phenotype is still unclear. We systematically searched Medline, Embase, and the Cochrane databases for studies assessing the genetic basis of host response to UVR DNA damage, the effect of UVR on generation of reactive oxygen species (ROS), and their detoxification, UVR induced skin immunity modifications, and the role of genomic instability with a focus on the potential use of these biomarkers to the surgical treatment planning and prognosis of BCC patients. Data suggest that risk for BCC development is likely to result from the combined effect of many genes, each with a relatively weak individual contribution. Certain genomic alterations have been associated with increased or reduced risk for BCC development, with a second primary BCC or with recurrence of BCC. However, use of these biomarkers in everyday practice should be supported by further studies, mainly for its cost-effectiveness. In addition, not enough information exists on the prognostic value of existing demographic and clinical risk predictors for BCC regarding development of second primary or recurrent tumors. Information reviewed suggests that these predictors are of higher predictive value compared with biomarkers whilst they are indisputably cheaper and easier to monitor even in developing countries. Conclusively, we suggest that further studies aimed in investigating second primary or recurrent BCC are needed to provide better information on the predictive value of certain demographic, clinical and histological factors.

Regional Differences in Cerebral Edema After Traumatic Brain Injury Identified by Impedance Analysis

2008-11-27

Objective: Cerebral edema is a common and potentially devastating sequel of traumatic brain injury. We developed and validated a system capable of tissue impedance analysis, which was found to correlate with cerebral edema.Methods: Constant sinusoidal current (50 μA), at frequencies from 500 to 5000 Hz, was applied across a bipolar electrode unit superficially placed in a rat brain after traumatic brain injury. Rats were randomized to three groups: severe controlled cortical injury (CCI), mild CCI, or sham injury. At 60 h post-CCI, cerebral voltage and phase angle were measured at each frequency at the site of injury, at the penumbral region, at the ipsilateral frontal region, and in the contralateral hemisphere. Impedance measurements were also obtained in vivo. The electrical properties of varied injuries and specified locations were compared using a repeated measures analysis of variance (RMANOVA), were correlated with regional tissue water percentage using regression analyses, and were combined to generate polar coordinates.Results: The measured voltage was significantly different at the site of injury (P < 0.0001), in the penumbra (P = 0.002), and in the contralateral hemisphere (P = 0.005) when severe, mild, and sham CCI rats were compared. Severely injured rats had statistically different voltage measurements when the various sites were compared (P = 0.002). The ex vivo measurements correlated with in vivo measurements. Further, the impedance measurements correlated with measured tissue water percentage at the site of injury (R2 = 0.69; P < 0.0001). The creation of a polar coordinate graph, incorporating voltage and phase angle measurements, enabled the identification of impedance areas unique to normal, mild edema, and severe edema measurements in the rat brain.Conclusions: Electrical measurements and tissue water percentages quantified regional and severity differences in rat brain edema after CCI. Impedance was inversely proportional to the tissue water percentage. Thus, impedance measurement can be used to quantify severity of cerebral edema in real time at specific sites.

Cyclic AMP Inhibits IL-1β Plus IFNγ-Induced NF-κB Translocation in Hepatocytes by a PKA Independent Mechanism

Guiying Hong, Baochun Zhang, Brian G. Harbrecht — 2009-01-12

We previously showed that cAMP inhibits IL-1β plus IFNγ-induced NF-κB binding in primary hepatocytes but the signaling mechanisms responsible for this effect are not understood. In this study, the role of PKA in mediating the effect of cAMP on NF-κB was investigated. Immunofluorescent staining showed that cAMP inhibited IL-1β plus IFNγ-induced translocation of NF-κB into the nucleus. Western blot analysis showed that the IL-1β plus IFNγ- induced phosphorylation and degradation of IκBa were markedly inhibited by cAMP. Immunocomplex assay involving GST-IKK revealed that cAMP inhibited IL-1β plus IFNγ-induced IKK activity. The PKA inhibitors had no effect on the inhibition of NF-κB binding by cAMP and did not change the p65 and IKB level induced by cAMP. Overexpression of PKA increased IL-1β plus IFNγ-induced NF-κB binding. These results suggest that PKA is not essential for the inhibitory effect of cAMP on NF-κB binding activity in hepatocytes. We demonstrated that cAMP inhibits IL-1β plus IFNγ-induced NF-κB binding due to its blockade of the upstream signal(s) leading to IκB phosphorylation and degradation, and is mediated by PKA-independent signaling pathways.

Plateau and Transpulmonary Pressure With Elevated Intra-Abdominal Pressure or Atelectasis

2009-09-07

Background: ARDSnet standards limit plateau pressure (Pplat) to reduce ventilator induced lung injury (VILI). Transpulmonary pressure (Ptp) [Pplat –pleural pressure (Ppl)], not Pplat, is the distending pressure of the lung. Lung distention can be affected by increased intra-abdominal pressure (IAP) and atelectasis. We hypothesized that the changes in distention caused by increases in IAP and atelectasis would be reflected by Ptp but independent of Pplat.Methods: In Yorkshire pigs, esophageal pressure (Pes) was measured with a balloon catheter as a surrogate for Ppl under two experimental conditions: (1) high IAP group (n=5), where IAP was elevated by CO2 insufflation in 5mm Hg steps from 0 to 30mm Hg; and (2) Atelectasis group (n=5), where a double lumen endotracheal tube allowed clamping and degassing of either lung by O2 absorption. Lung collapse was estimated by increases in pulmonary shunt fraction.Results: High IAP: Sequential increments in IAP caused a linear increase in Pplat (r2=0.754, P<0.0001). Ptp did not increase (r2=0.014, P=0.404) with IAP due to the concomitant increase in Pes (r2=0.726, P<0.0001). Partial Lung Collapse: There was no significant difference in Pplat between the atelectatic (21.83±0.63cm H2O) and inflated lung (22.06±0.61 cmH2O, P<0.05). Partial lung collapse caused a significant decrease in Pes (11.32±1.11mm Hg) compared with inflation (15.89±0.72mm Hg, P<0.05) resulting in a significant increase in Ptp (inflated=5.97±0.72mm Hg; collapsed=10.55±1.53mm Hg, P<0.05).Conclusions: Use of Pplat to set ventilation may under-ventilate patients with intra-abdominal hypertension and over-distend the lungs of patients with atelectasis. Thus, Ptp must be used to accurately set mechanical ventilation in the critically ill.

Preservation Solutions Alter Mrp2-Dependent Bile Flow in Cold Ischemic Rat Livers

2009-01-28

Background: Previously, decreased organic anion transport through multidrug resistance protein 2 (Mrp2) was observed without any notable cell lysis, even when the livers were stored for 8 hours in University of Wisconsin solution (UW). The aim of this study was to examine the bile flow and its constituents, markers of graft dysfunction without necrosis in cold ischemic livers, using the following preservation media: UW, ET-Kyoto solution (ET-K) and histidine-tryptophan-ketoglutarate solution (HTK).Materials and Methods: Rat livers were stored at 4°C for 8 hours in the preservation media, and reperfused to collect the bile and determine their constituents. Glycyrrhizin (GL) and/or glutathione (GSH) were added to the media as necessary. The transport efficiency of Mrp2 was assessed by the biliary excretion of 5-carboxyfluorescein (CF), a fluoroprobe excreted from Mrp2. The Intracellular distribution of Mrp2 was determined by immunostaining.Results: Livers stored for 8 hours exhibited significantly decreased bile production and biliary glutathione (GSH) levels without notable cell lysis. CF excretion was significantly delayed in all solutions. However, these markers were remarkably improved by the redistribution of Mrp2 from the cytoplasm to the canalicular membrane, when the livers were exposed to UW in the presence of GL. Moreover, livers exposed to the Kyoto and HTK solutions increased their bile production and organic anion transport in the presence of GL and GSH.Conclusion: These results suggest that the addition of GL and GSH to preservation solutions improves bile production and biliary organic anion transport by increasing Mrp2 localization to the bile canaliculi in post-cold ischemic livers. (248 words).

Knockdown of Interleukin-2 by shRNA-Mediated RNA Interference Prolongs Liver Allograft Survival

2008-10-15

Interleukin-2 (IL-2) plays a central role in T-cell activation, expansion, and homeostasis. The failure of IL-2 biosynthesis may play a critical role in tolerance induction. We tested the effect of IL-2 blockade by short hairpin RNA (shRNA) on regulating acute rejection in rat liver transplantation. To this end, we successfully designed and selected an effective interference plasmid, pIL-2B. The IL-2 mRNA expression level in the pIL-2B group was one-fifth of that in the no transfection group. Lewis to BN orthotopic liver transplant model was used to explore the effect of knockdown IL-2 by shRNA in vivo. Recipients treated with pIL-2-shRNA survived longer (median survival time of 16 d range 7–21 d) than those with empty vector (11; range 5–13) or saline (9; range 5–13) (P < 0.05), and was inferior to those with CsA (24; range 13–36, P < 0.05). The IL-2-shRNA attenuated acute rejection with decreased apoptosis of hepatocytes and reduced cytokine production of IL-2, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) in the graft. Our results suggest that IL-2 targeting using RNA interference approach may be of potential interest in organ transplantation.

Protective Potential of Montelukast Against Hepatic Ischemia/Reperfusion Injury in Rats

2008-09-09

Ischemia and reperfusion (I/R) injury is characterized by significant oxidative stress, characteristic changes in the antioxidant system and organ injury leading to significant morbidity and mortality. This study was designed to assess the possible protective effect of montelukast, a selective antagonist of cysteinyl leukotriene receptor 1 (CysLT1), on hepatic I/R injury in rats. Wistar albino rats through clamping hepatic artery, portal vein, and bile duct, were subjected to 45 min of hepatic ischemia followed by 60 min reperfusion period. Montelukast (10 mg/kg; i.p.) was administered 15 min prior to ischemia and immediately before reperfusion period. At the end of the reperfusion period, the rats were killed by decapitation. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) activity, and proinflammatory cytokines (TNF-α and IL-1β) were determined in blood samples. Malondialdehyde (MDA), and glutathione (GSH) levels and myeloperoxidase (MPO) and Na+, K+-ATPase activities were determined in the liver tissue samples while formation of reactive oxygen species was monitored by using chemiluminescence (CL) technique with luminol and lucigenin probes. Tissues were also analyzed histologically. Serum ALT, AST, and LDH activities were elevated in the I/R group, while this increase was significantly decreased by montelukast treatment. Hepatic GSH levels and Na+, K+-ATPase activity, significantly depressed by I/R, were elevated back to control levels in montelukast-treated I/R group. Furthermore, increases in tissue luminol and lucigenin CL, MDA levels, and MPO activity due to I/R injury were reduced back to control levels with montelukast treatment. Since montelukast administration alleviated the I/R-induced liver injury and improved the hepatic structure and function, it seems likely that montelukast with its anti-inflammatory and antioxidant properties may be of potential therapeutic value in protecting the liver against oxidative injury due to ischemia-reperfusion.

The Impact of Surgical Specialty on Outcomes for Carotid Endarterectomy

2008-05-13

Background: Carotid endarterectomy (CEA) is one of the most frequently performed surgical procedures in the United States. Traditionally, this procedure has been performed by surgeons in at least four specialties. The purpose of this study was to examine the effect of surgeon specialty on the long-term outcomes of CEA among patients receiving the procedure in Pennsylvania.Materials and methods: Data included 17,635 patient admissions for CEA performed between 1995 and 1997, and patient readmission data for the 5-y follow-up period ending in 2002. Five-y outcomes for these patients were compared between vascular, cardiothoracic, general, and neurosurgeons. The primary outcome measures were mortality, stroke, combined stroke and mortality, transient ischemic attack (TIA), and re-occlusion of the ipsilateral artery. Secondary outcomes measured were length of stay and total charges.Results: Using general surgeon as the reference group, and controlling for age, race, severity, and admission type, we found no significant difference across surgical specialties in overall mortality at 5 y post-CEA. Patients treated by vascular surgeons were found to have significantly fewer (P = 0.012) strokes and significantly lower re-occlusion rate (P = 0.021) at 5 y compared with patients of general surgeons. Patients treated by vascular surgeons also had significantly shorter hospital stay (P < 0.0001) but significantly higher charges (P < 0.0001) relative to general surgeons.Conclusions: These results suggest that there are significant differences in outcomes following carotid endarterectomy according to surgeon training. Additional research is needed to explore differences across specialties that may be driving outcomes and to explore the role of surgeon volume at the profession level and cross-volume effects on CEA outcomes.

Carnitine Protects the Intestine Against Reperfusion Injury in Rats

2009-04-23

Background: Although the negative effects of ischemia on anastomotic healing have been shown in many studies, there is no adequate information on the effects of reperfusion injury. Therefore, in this study, we investigated the effect of ischemia-reperfusion (IR) injury on intestinal anastomosis and the protective efficiency of carnitine in an experimental relatively short intestinal ischemia and long duration reperfusion model.Methods: Animals were divided into three groups (n=14). Each group was separated into two subgroups. In subgroups A, morphologic injury and the number of perfused intestinal muscular microvessels were analyzed to show “no-reflow phenomenon.” Intestinal resection and anastomosis were performed in subgroups B. Carnitine group (IRCarG) received 200mg/kg intravenous carnitine 2min prior to reperfusion. Malonyldialdehyde, nitric oxide levels in tissue and blood, collagen levels, bursting pressures, and histopathologic evaluation of anastomosis were measured in subgroups B.Results: Morphologic damage was statistically lower, number of perfused microvessels and epithelial regeneration were statistically higher in IRCarG, compared with ischemia-reperfusion group (P=0.03, P=0.008, P=0.05, respectively).Conclusion: Carnitine application prior to reperfusion may reduce the severity of the reperfusion injury by preventing the occurrence of no-reflow phenomenon, increase the number of perfused microvessels in the ischemic intestine, and may improve epithelial regeneration in intestinal anastomosis.

Decrease in Wound Tensile Strength Following Post-Surgical Estrogen Replacement Therapy in Ovariectomized Rats During the Early Phase of Healing is Mediated Via ER-α Rather than ER-β: A Preliminary Report

2009-04-01

Background: In cases of acute surgery or trauma, the most effective method of increasing the level of estrogen in postmenopausal women is its administration immediately pre- or postsurgery. However, in our previous study (J Surg Res 2008; 147:117-122) we showed that postsurgical administration of nonspecific estrogen receptor (ER) agonist decreases wound tensile strength. Therefore, the aim of this study was to evaluate whether this effect is mediated via the α or β ER.Materials and Methods: Three months prior to the wound healing experiment, 18 rats were anesthetized and underwent ovariectomy (OVX), while another six rats were sham operated. Two parallel full thickness skin incisions were performed on the back of each rat. Doses of 1mg/kg of either PPT (ER-α agonist) or DPN (ER-β agonist) were administered to 12 OVX rats for 6 d postoperatively, whereas all other animals received vehicle. After 6 d, all animals were sacrificed and samples removed for wound tensile strength measurement and histologic evaluation.Results: The mean wound tensile strength of PPT-treated rats (6.8±1.9g/mm2) was significantly lower compared with all other groups (P<0.05). No significant differences were observed between DPN-treated (8.9±2.2g/mm2), non-OVX vehicle-treated (8.7±2.0g/mm2), and OVX vehicle-treated (9.1±1.7g/mm2) rats. Nevertheless, no remarkable differences were found between groups during histologic evaluation.Conclusion: Our results indicate that the wound tensile strength decrease is mediated through the α rather than β ER.

Topical Dissolved Oxygen Penetrates Skin: Model and Method

David F. Roe, Bruce L. Gibbins, Daniel A. Ladizinsky — 2009-11-23

Background: It has been commonly perceived that skin receives its oxygen supply from the internal circulation. However, recent investigations have shown that a significant amount of oxygen may enter skin from the external overlying surface. A method has been developed for measuring the transcutaneous penetration of human skin by oxygen as described herein. This method was used to determine both the depth and magnitude of penetration of skin by topically applied oxygen.Material and Methods: An apparatus consisting of human skin samples interposed between a topical oxygen source and a fluid filled chamber that registered changes in dissolved oxygen. Viable human skin samples of variable thicknesses with and without epidermis were used to evaluate the depth and magnitude of oxygen penetration from either topical dissolved oxygen (TDO) or topical gaseous oxygen (TGO) devices.Results and Conclusion: This model effectively demonstrates transcutaneous penetration of topically applied oxygen. Topically applied dissolved oxygen penetrates through >700 μm of human skin. Topically applied oxygen penetrates better though dermis than epidermis, and TDO devices deliver oxygen more effectively than TGO devices.

Editorial Board

2010-03-01

Subscription Information

2010-03-01

Information for Authors

2010-03-01

Journal of Surgical Research

Caveolin-1 Regulating the Invasion and Expression of Matrix Metalloproteinase (MMPs) in Pancreatic Carcinoma Cells

Hydrogen Sulfide Protects Against Ischemia-Reperfusion Injury in an In Vitro Model of Cutaneous Tissue Transplantation1

Physical Examination is a Poor Screening Test for Abdominal-Pelvic Injury in Adult Blunt Trauma Patients

Teaching Breaking Bad News Using Mixed Reality Simulation

A Different View of Lactate in Trauma Patients: Protecting the Injured Brain

Identification of a Novel Potential Biomarker in a Model of Hemorrhagic Shock and Valproic Acid Treatment1

The Johns Hopkins Surgery ABSITE Review Manual

Commentary

Pediatric FAST and Elevated Liver Transaminases: An Effective Screening Tool in Blunt Abdominal Trauma

The Dying Field of General Surgery: When Do We Intervene? Why Residents Choose to Specialize in Fields Outside Surgery

Prospective Randomized Study for Comparison of Open Surgery with Laparoscopic-Assisted Placement of Tenckhoff Peritoneal Dialysis Catheter—A Single Center Experience and Literature Review

Curcumin Attenuates Oxidative Stress and Inflammatory Response in the Early Phase after Partial Hepatectomy with Simultaneous Intraabdominal Infection in Rats

The Effects of Different Nutritional Measurements on Delayed Wound Healing After Hip Fracture in the Elderly

Ischemia-Reperfusion Injury in Skeletal Muscle: Comparison of the Effects of Subanesthetic Doses of Ketamine, Propofol, and Etomidate

Pretreatment with Dexmedetomidine or Thiopental Decreases Myoclonus after Etomidate: A Randomized, Double-Blind Controlled Trial

Prognostic Criteria for Squamous Cell Cancer of the Skin

The Role of VEGF Pathways in Human Physiologic and Pathologic Angiogenesis

Mammography as a Screening Tool for Diabetes

Radiofrequency Ablation of Liver Tumors: A Novel Needle Perfusion Technique Enhances Efficiency

LCSGJ-T Classification, 6th or 5th Edition TNM Staging Did Not Independently Predict the Long-Term Prognosis of HBV-Related Hepatocellular Carcinoma After Radical Hepatectomy

New Concepts for Basal Cell Carcinoma. Demographic, Clinical, Histological Risk Factors, and Biomarkers. A Systematic Review of Evidence Regarding Risk for Tumor Development, Susceptibility for Second Primary and Recurrence

Regional Differences in Cerebral Edema After Traumatic Brain Injury Identified by Impedance Analysis

Cyclic AMP Inhibits IL-1β Plus IFNγ-Induced NF-κB Translocation in Hepatocytes by a PKA Independent Mechanism

Plateau and Transpulmonary Pressure With Elevated Intra-Abdominal Pressure or Atelectasis

Preservation Solutions Alter Mrp2-Dependent Bile Flow in Cold Ischemic Rat Livers

Knockdown of Interleukin-2 by shRNA-Mediated RNA Interference Prolongs Liver Allograft Survival

Protective Potential of Montelukast Against Hepatic Ischemia/Reperfusion Injury in Rats

The Impact of Surgical Specialty on Outcomes for Carotid Endarterectomy

Carnitine Protects the Intestine Against Reperfusion Injury in Rats

Decrease in Wound Tensile Strength Following Post-Surgical Estrogen Replacement Therapy in Ovariectomized Rats During the Early Phase of Healing is Mediated Via ER-α Rather than ER-β: A Preliminary Report

Topical Dissolved Oxygen Penetrates Skin: Model and Method

Editorial Board

Subscription Information

Contents

Information for Authors