Citations

Abstract Background: Previous comparisons of monoclonal protein quantification identified a bias between serum protein electrophoresis (SPEP) and immunonephelometry (NEPH). Methods: We reviewed data from 2845 patients in whom a single sample provided a γ fraction M-spike by SPEP, a heavy chain isotype by immunofixation electrophoresis (IFE), and an Ig quantification by NEPH. We examined the relationship between SPEP and NEPH. Selected sera with high monoclonal protein concentrations were diluted and reassessed. Results: For all isotypes, the relationship between SPEP and NEPH was best fitted with cubic curves. We determined the concentrations of each isotype that fitted a linear relationship. IgA had the best correspondence (slope 0.92, 95% CI 0.87–1.02), whereas IgM demonstrated a systematic bias of higher values by NEPH (slope 1.80, 95% CI 1.68–1.92). IgG demonstrated a nonlinear relationship between SPEP and NEPH, with a linear region <19.2 g/L having a slope of 0.83 (95% CI 0.79–0.89) and a second linear region having a slope of 1.47 (95% CI 1.39–1.53) at higher concentrations. Dilutions of high-concentration IgG monoclonal proteins were linear by NEPH and nonlinear by SPEP. Conclusions: There are systematic differences in the quantification of monoclonal IgM and IgG by SPEP and NEPH. The bias in IgM is from NEPH overestimation. The nonlinearity of SPEP at high monoclonal IgG concentrations may obscure changes in plasma cell populations. Clinicians should be made aware of the biases and nonlinearity in these tests to make proper conclusions regarding treatment response.

Background Paraplegia is a devastating complication for patients undergoing repair of thoracoabdominal aortic aneurysms. A monitor to detect spinal cord ischemia is necessary if anesthesiologists are to intervene to protect the spinal cord during aortic aneurysm clamping. Methods The medical records of 60 patients who underwent thoracoabdominal aortic aneurysm repair with regional lumbar epidural cooling with evoked potential monitoring were reviewed. The authors analyzed latency and amplitude of motor evoked potentials, somatosensory evoked potentials, and H reflexes before cooling and clamping, after cooling and before clamping, during clamping, and after release of aortic cross clamp. Results Twenty minutes after the aortic cross clamp was placed, motor evoked potentials had 88% sensitivity and 65% specificity in predicting spinal cord ischemia. The negative predictive value of motor evoked potentials at 20 min after aortic cross clamping was 96%. Conclusions Rapid loss of motor evoked potentials or H reflexes after application of the aortic cross clamp identifies a subgroup of patients who are at high risk of developing spinal cord ischemia and in whom aggressive anesthetic and surgical interventions may be justified.

ABSTRACT We analyzed surveillance cultures for vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA) collected during a multicenter trial to determine if three negative cultures collected at weekly intervals would predict clearance of VRE or MRSA from colonized patients. Seventy-two percent of VRE-colonized patients and 94% of MRSA-colonized patients were culture negative after three consecutive negative cultures.

Abstract Colon cancer develops over a period of 10 to 15 years, providing a window of opportunity for chemoprevention and early intervention. However, few molecular targets for effective colon cancer chemoprevention have been characterized and validated. Protein kinase CβII (PKCβII) plays a requisite role in the initiation of colon carcinogenesis in a preclinical mouse model by promoting proliferation and increased β-catenin accumulation. In this study, we test the hypothesis that PKCβII is an effective target for colon cancer chemoprevention using enzastaurin (LY317615), a PKCβ-selective inhibitor, in a mouse model of colon carcinogenesis. We find that enzastaurin potently reduces azoxymethane-induced colon tumor initiation and progression by inhibiting PKCβII-mediated tumor cell proliferation and β-catenin accumulation. Biochemically, enzastaurin reduces expression of the PKCβII- and β-catenin/T-cell factor–regulated genes PKCβII, cyclooxygenase II, and vascular endothelial growth factor, three genes implicated in colon carcinogenesis. Our results show that enzastaurin is an effective chemopreventive agent in a mouse model of sporadic colon cancer that significantly reduces both tumor initiation and progression by inhibiting expression of proproliferative genes. Thus, PKCβII is an important target for colon cancer chemoprevention and the PKCβ-selective inhibitor enzastaurin may represent an effective chemopreventive agent in patients at high risk for colon cancer. [Cancer Res 2009;69(4):1643–50]

Abstract The economics of medicine have drastically changed during the past quarter century. Institutions may be faced with difficult decisions concerning graduate medical education (GME), particularly as it relates to the growth of existing programs and the creation of new programs. The authors describe a tool that they developed that can consistently measure the value of individual training programs while aligning with an institution's strategic priorities. This tool, the assessment metric scorecard, permits the annual prioritization of GME programs by the leadership of Mayo Clinic, Jacksonville, Florida. The scorecard also provides valuable data regarding the strengths and weaknesses of individual programs. The metric seeks to evaluate GME programs on the basis of four broad areas: Research, Teaching, Patient Service, and a General category. The assessment metric scorecard has been used since 2004; this article reports on its use for the academic years 2004–2005 and 2005–2006. The scorecard has proved to be a helpful tool for the yearly evaluation and prioritization of GME programs at the authors' institution. The overall mean score of the GME programs increased, which suggests a positive trend. This scorecard is flexible; modifications of the relative weights of the metrics can be made to align it with the strategic priorities of other institutions. The resources necessary to implement the scorecard are minimal.

Abstract We previously showed that elevated expression of either protein kinase CβII (PKCβII) or PKCι/λ enhances colon carcinogenesis in mice. Here, we use novel bitransgenic mice to determine the relative importance of PKCβII and PKCι/λ in colon carcinogenesis in two complimentary models of colon cancer in vivo. Bitransgenic mice overexpressing PKCβII and constitutively active PKCι (PKCβII/caPKCι) or kinase-deficient, dominant-negative PKCι (PKCβII/kdPKCι) in the colon exhibit a similar increase in colon tumor incidence, tumor size, and tumor burden in response to azoxymethane (AOM) when compared with nontransgenic littermates. However, PKCβII/kdPKCι mice develop predominantly benign colonic adenomas, whereas PKCβII/caPKCι mice develop malignant carcinomas. In contrast, PKCβ-deficient (PKCβ−/−) mice fail to develop tumors even in the presence of caPKCι. Our previous data indicated that PKCβII drives tumorigenesis and proliferation by activating β-catenin/Apc signaling. Consistent with this conclusion, genetic deletion of PKCβ has no effect on spontaneous tumorigenesis in Apcmin/+ mice. In contrast, tissue-specific knockout of PKCλ significantly suppresses intestinal tumor formation in Apcmin/+ mice. Our data show that PKCβII and PKCι/λ serve distinct, nonoverlapping functions in colon carcinogenesis. PKCβII is required for AOM-induced tumorigenesis but is dispensable for tumor formation in ApcMin/+ mice. PKCι/λ promotes tumor progression in both AOM- and Apcmin/+-induced tumorigenesis. Thus, PKCβII and PKCι, whose expression is elevated in both rodent and human colon tumors, collaborate to drive colon tumor formation and progression, respectively. [Cancer Res 2009;69(2):656–62]

Abstract Rationale Idiopathic pulmonary fibrosis (IPF) is characterized by progressive dyspnea, impaired gas exchange, and ultimate mortality. Objectives To test the hypothesis that maximal oxygen uptake during cardiopulmonary exercise testing at baseline and with short-term longitudinal measures would predict mortality in patients with idiopathic pulmonary fibrosis. Methods Data from 117 patients with IPF and longitudinal cardiopulmonary exercise tests were examined retrospectively. Survival was calculated from the date of the first cardiopulmonary exercise test. Measurements and Main Results Patients with baseline maximal oxygen uptake less than 8.3 ml/kg/min had an increased risk of death (n = 8; hazard ratio, 3.24; 95% confidence interval, 1.10–9.56; P = 0.03) after adjusting for age, gender, smoking status, baseline forced vital capacity, and baseline diffusion capacity for carbon monoxide. We were unable to define a unit change in maximal oxygen uptake that predicted survival in our cohort. Conclusions We conclude that a threshold maximal oxygen uptake of 8.3 ml/kg/min during cardiopulmonary exercise testing at baseline adds prognostic information for patients with IPF.

Paraplegia is a major complication associated with repair of thoracoabdominal aortic aneurysms (TAAA). A number of therapies have been tried over the years, none of which has been successful. Recently, regional lumbar epidural cooling has been tried in an attempt to prolong the safe ischemic time during aortic cross- clamping. In approximately 90 patients in whom the authors have tried this technique, there was no de crease in the incidence of paraplegia in patients with type II TAAAs. This is perhaps not unanticipated be cause the paraplegia is related to a number of factors including the duration of the aortic cross-clamping, the adequacy of collateral circulation, embolization during the procedure, and perhaps thrombosis in situ. Given the multimodal cause of paraplegia, perhaps it is naive to think that a single therapy would be of benefit. Additional studies are necessary to explore the mecha nisms and to prove efficacy or lack of benefit of any techniques designed to decrease the incidence of paraplegia in patients undergoing TAAA repair.