Iodide Improves Outcome After Acute Myocardial Infarction in Rats and Pigs.

OBJECTIVES: In this study, we tested whether iodide would reduce heart damage in rat and pig models of acute myocardial infarction as a risk analysis for a human trial. DESIGN: Prospective blinded and randomized laboratory animal investigation. SETTING: Animal research laboratories. SUBJECTS: Sexually mature rats and pigs. INTERVENTIONS: Acute myocardial infarction was induced by temporary ligation of the coronary artery followed by reperfusion. Iodide was administered orally in rats or IV in rats and pigs just prior to reperfusion. MEASUREMENTS AND MAIN RESULTS: Damage was assessed by blood cardiac troponin and infarct size; heart function was determined by echocardiography. Blood peroxide scavenging activity was measured enzymatically, and blood thyroid hormone was determined using radioimmune assay. Iodide administration preserved heart function and reduced blood cardiac troponin and infarct size by approximately 45% in pigs and approximately 60% in rats. Iodide administration also increased blood peroxide scavenging activity and maintained thyroid hormone levels. CONCLUSIONS: Iodide administration improved the structure and function of the heart after acute myocardial infarction in rats and pigs.

A Global Assessment of Access to and Use of Medical Information: The State of Evidence-Based Surgery.

BACKGROUND: We aimed to assess surgeons' access to and use of medical information, as well as their training and perceptions about evidence-based medicine (EBM), in order to identify priority areas for improvement. STUDY DESIGN: An anonymous survey conducted among surgeons from the USA, Ghana, Peru, and Thailand examined access to, and use and perception of, medical literature. RESULTS: Of 307 participants, 98% reported access to "OK" or "good" internet. Fifty-one percent reported that language was a barrier to accessing needed medical information; most frequently in Peru (73%) and Thailand (64%). Access to priced full-text journals was poorest in Peru, where 54% lacked access, followed by Ghana (42%) and Thailand (32%). US respondents scored highest on the EBM knowledge test (1.4, SD 0.8), followed by Thailand (1.3, SD 0.9), Ghana (1.1, SD 0.8), and Peru (0.9, SD 0.8) (p < 0.001). Adjusted analysis revealed Ghanaians and Peruvians spent 5% and 1% more on medical information, respectively, relative to country income, than persons from other countries (p < 0.01). After adjustment, employment in a large and/or urban hospital and history of EBM training were associated with better EBM test scores, while middle-income origin and public hospital employment were associated with worse scores (p < 0.05). CONCLUSION: Language, access to priced full-text journals, and training are significant barriers to surgeons' practice of EBM globally. The way forward involves collaboration among surgical societies, publishers, hospital employers, and international policymakers in providing surgeons from all country income levels with the access and training necessary to interpret and apply medical information.

Correction to: A Global Assessment of Access to and Use of Medical Information: The State of Evidence-Based Surgery.

In the original article some funding information was inadvertently omitted. The complete funding information is as follows.

Hepatocellular heme oxygenase-1: a potential mechanism of erythropoietin-mediated protection after liver ischemia-reperfusion injury.

Hepatic ischemia-reperfusion (IR) results in progressive injury; initiated by oxidative stress during ischemia and compounded by cytokine-mediated inflammation during reperfusion. Recovery requires strict regulation of these events. Recombinant human erythropoietin (rhEPO) is thought to mitigate hepatocellular IR injury by altering the nonparenchymal liver microenvironment. This study sought to identify additional mechanisms whereby rhEPO is protective after liver IR injury. Mice were treated with rhEPO (4 units/g s.c.) at the onset of partial liver ischemia and assessed for transaminase and histologic injury at intervals after reperfusion. Induction of cytokines, activation of signal transducers and activators of transcription (STATs), suppressors of cytokine signaling (Socs1, Socs3, Cis), caspase-3 activation, and heme oxygenase-1 (HO-1) expression were assessed in postischemic liver. Effects of rhEPO stimulation were further characterized in whole-liver lysates from mice undergoing rhEPO injection alone and in cultured AML-12 hepatocytes. Recombinant human erythropoietin treatment at the onset of severe (90 min) hepatic IR confirmed commensurate biochemical and histological protection without affecting tissue cytokine levels. Although Socs3 and STAT5 activation were induced in normal liver after in vivo rhEPO injection, this treatment did not augment expression beyond that seen with IR alone, and neither was induced in cultured hepatocytes treated with rhEPO. Recombinant human erythropoietin inhibited caspase-3 activation in nonparenchymal cells, whereas hepatocellular HO-1 was rapidly induced both in vivo and in vitro with rhEPO treatment. These data suggest HO-1 as a potent mechanism of rhEPO-mediated protection after liver IR, which involves both direct hepatocellular and nonparenchymal mechanisms.

Expanding surgical clerkships to remote community sites: the success of the Washington, Wyoming, Alaska, Montana, and Idaho experience.

BACKGROUND: The purpose of this analysis was to determine if the surgical clerkship model and site affect educational outcomes and student postclerkship perceptions. METHODS: Data from University of Washington students participating in surgical clerkships at traditional/academic or community/apprentice sites across Washington, Wyoming, Alaska, Montana, and Idaho (WWAMI) between 2005 and 2007 were gathered retrospectively. Comparisons of final examination scores as well as postclerkship student evaluations of the educational experience were made between traditional and community training sites. RESULTS: The mean final examination scores at WWAMI sites were significantly higher than those at traditional academic sites. Furthermore, WWAMI sites were rated higher with respect to time spent by faculty in direct observation, quality of the clerkship as a whole, and overall contribution to medical education. CONCLUSIONS: Community surgical clerkship sites remote from an academic institution can provide an excellent learning experience for students.

Suppressor of cytokine signaling expression with increasing severity of murine hepatic ischemia-reperfusion injury.

BACKGROUND/AIMS: Preservation of function requires tight regulation of the cellular events initiated when hepatic ischemia is followed by reperfusion (IR). One important mechanism modulating the cytokine-directed response to injury is Suppressors of Cytokine Signaling. SOCS1 and SOCS3 ensure appropriate intensity and duration of cytokine signaling through negative feedback on JAK-STAT signaling. The contribution of SOCS1 and SOCS3-mediated regulation to the evolution of hepatic IR injury is unknown. METHODS: C57Blk6 mice were subjected to mild (20 min) or severe (90 min) hepatic ischemia. Liver was analyzed for cytokine and SOCS1/3 induction as well as JAK-STAT activation at intervals after reperfusion. RESULTS: Tnf, Il-1beta, and Il-6 expression paralleled increasing injury severity. Despite early phosphorylation of both STAT1 and STAT3 after severe injury, only nuclear translocation of activated STAT3, suggesting that the induction of target genes through JAK-STAT after IR is predominantly via STAT3. Socs3 was expressed across the injury spectrum while Socs1 was induced only in the face of severe IR injury. Severe IR in Il-6 deficient mice confirmed that Il-6, acting via STAT3, serves as a primary inducer of both regulatory mechanisms. CONCLUSIONS: Under the influence of IL-6-mediated STAT3 signaling, Socs1 serves as a complimentary regulatory mechanism when Socs3 is insufficient to limit cytokine-mediated inflammation after hepatic IR.

Clinical utility and cost-effectiveness of routine preoperative computed tomography scanning in patients with colon cancer.

BACKGROUND: The aims of this study were to assess the clinical utility of the practice of routine preoperative CT scanning and to determine its cost-effectiveness in colon cancer patients. METHODS: A 6-year database of colon cancer patients treated at a veterans affairs medical was reviewed to determine the influence of preoperative CT scanning on clinical management. Cost analysis involved comparison of the institutional cost of CT scanning with the cost savings provided by avoiding nontherapeutic operations. RESULTS: CT scans were obtained in 130 consecutive patients. CT scans provided information that was used in treatment planning in 43 (33%) patients and definitively altered the mode of treatment in 21 (16%) patients. The practice saved the institution $24,018 over 6 years. CONCLUSION: Routine preoperative CT scanning definitively alters treatment in a small number of cases and is cost-effective.

Sustained tolerance to lipopolysaccharide after liver ischemia-reperfusion injury.

Liver ischemia-reperfusion injury (IR) would be expected to alter the capacity of previously ischemic as well as continuously perfused segments that are exposed to circulating inflammatory mediators to respond to a subsequent infectious insult. IR is reported to induce tolerance to subsequent endotoxin stimulation if the lipopolysaccharide (LPS) challenge is delayed until the late, neutrophil-mediated phase of reperfusion. Whether ischemic or perfused liver is differentially affected and whether LPS-tolerance may be overcome by increasing exposure is unknown. We hypothesized that late tolerance after IR reflects a refractory state in which the liver's expression of pro-inflammatory mediators in response to secondary LPS is limited. Precision-cut tissue culture methodology was used to investigate the capacity of rabbit liver to respond to a spectrum of LPS stimulation 24 h after partial IR. Slices from normal liver showed a dose-dependent response to LPS for tumor necrosis factor (TNF-alpha) expression. Slices from both previously ischemic and continuously perfused lobes retained dose responsiveness for TNF-alpha, although TNF-alpha was significantly decreased at high LPS concentrations compared with normal liver. Ischemic liver sustained this blunted response despite extended exposure to LPS, whereas perfused slices recovered responsiveness to high dose LPS with prolonged stimulation. IR induced interleukin-8 in both ischemic and perfused liver, but secondary LPS stimulation did not augment interleukin-8 expression. Hepatic IR induces a late tolerance to secondary LPS challenge in locally ischemic tissue that cannot be overcome by increasing LPS exposure. Nonischemic liver exposed to the systemic effects of IR injury, however, retains a capacity to respond to LPS with sufficient stimulation.

Preparing graduates for the first year of residency: are medical schools meeting the need?

PURPOSE: Changes in graduate medical education associated with full implementation of the Balanced Budget Act of 1997 have required medical schools to review and revise their curricula. As limited funding increases pressures to streamline training, residencies will potentially expect an entry level of skill and competence that is greater than that which schools are currently providing. To determine whether medical school curricular requirements correlate with residency needs, this multidisciplinary pilot study investigated expectations and prerequisites for postgraduate specialty training. METHOD: A questionnaire about 100 skills and competencies expected of new first-year residents was sent to 50 U.S. residency directors from surgery, internal medicine, family medicine, pediatrics, and obstetrics-gynecology programs. Each director was asked to state expectations of a first-year resident's competence in each skill at entry to residency and after three months of training. Skills deemed most appropriately acquired in residency were also identified. Competencies included diagnosis, management, triage, interpretation of data, informatics and technology, record keeping, interpersonal communications, and manual skills. RESULTS: A total of 39 residency directors responded, including seven surgery, nine medicine, seven family medicine, eight pediatrics, and eight obstetrics-gynecology. In addition to physical examination skills, 13 competencies achieved more than 70% agreement as being entry-level skills. There was wide variability as to the relative importance of the remaining skills, with residency directors expecting to devote significant resources and time in early training to ensure competence. CONCLUSIONS: Medical schools should consider the expectations of their students' future residency directors when developing new curricula. Assuring students' competencies through focused curricular change should save both time and resources during residency.

The utility of routine preoperative computed tomography scanning in the management of veterans with colon cancer.

BACKGROUND: The aim of this study is to assess the clinical utility of routine preoperative computed tomography (CT) scanning in patients with cancer of the intraperitoneal colon. METHODS: From November 1997 to June 2001, all patients at VA Puget Sound Healthcare System with a diagnosis of colon cancer were referred for a preoperative CT scan. Medical records and operative notes were reviewed to determine the influence of preoperative CT on clinical management. RESULTS: Seventy patients received a CT per protocol. Preoperative CT provided information that was used in treatment planning and management in 26 (37%) cases. However, if preoperative scans had not been performed, the clinical management would have been definitively altered in only 13 (19%) patients. CONCLUSIONS: Although these data suggest potential benefit for routine preoperative CT scanning, we believe additional study, including cost analysis, should precede the adoption of CT scanning as a routine preoperative study in patients with colon cancer.