Epidermal growth factor receptor expression correlates with poor survival in gastric adenocarcinoma from Mexican patients: a multivariate analysis using a standardized immunohistochemical detection system.

The aim of the study was to determine epidermal growth factor receptor (EGFR) expression in gastric adenocarcinoma by standardized immunohistochemistry and to correlate EGFR expression with clinical features and patient survival. EGFR expression was investigated in paraffin sections of resection specimens of 89 gastric carcinomas from Mexican Mestizo patients using standardized immunohistochemistry with antigen retrieval (Dako EGFRpharmDx assay detection system). Membrane staining of EGFR was evaluated in the neoplastic cells and graded using a semiquantitative score (0-3+). Of the 89 carcinomas examined, staining of neoplastic cells was weak in 17 (19.1%, score 1+), moderate in 16 (18.0%, score 2+), and strong in nine cases (10.1%, score 3+). EGFR reactivity was heterogeneous, frequently showing completely negative up to 3+ positive areas within an individual tumor. EGFR reactivity score correlated with distant metastases (P=0.002) and clinical stage (P=0.033). EGFR score 0/1+ was significantly associated with an increase in patient survival when compared to score 2+/3+ (P=0.0006). In a multivariate analysis, EGFR positive cells in muscularis or subserosa (P=0.004), distant metastases (P=0.016) and residual disease (P=0.039) were significantly correlated with decreased survival. The prognosis was associated with the EGFR reactivity score (P=0.003), distant metastases (P=0.0001) and residual disease (P=0.012) in a univariate analysis. EGFR reactivity in neoplastic cells is an independent prognostic factor in gastric adenocarcinoma. The relevance of the heterogeneity in EGFR expression with regard to tumor progression, metastasis and anti-EGFR therapy needs to be studied.     

The influence of the causes and contexts of medical errors on emergency medicine residents' responses to their errors: an exploration.

PURPOSE: To determine emergency medicine residents' emotional and behavioral responses to their medical errors and examine associations between residents' responses to medical error and perceptions of their training. METHOD: In 2003, 55 residents at two U.S. residency programs were asked to complete questionnaires about their errors and responses to their errors in three domains: emotional response, learning behavior, and disclosure. The questions were a mixture of free text, yes/no responses, and some were rated using a five-point Likert scale. Based on a conceptual framework, the authors constructed scales to describe the various domains and associations between the residents' responses to medical error and perceptions of their training were examined using Somers' D. RESULTS: A total of 43 residents returned questionnaires (80%); 40 of these residents described errors. Thirty-three (83%) residents discussed the error with someone; 27 (71%) with the attending and 10 (28%) with the patient/family. Negative emotions were common: 27 (68%) felt remorse, 21 (53%) guilt, 23 (58%) inadequacy, and 22 (55%) frustration. Residents' negative emotional responses were associated with their personal characteristics [26% (95% CI, 5-47%) association with lack of experience] and residents' perceptions of their training environment: 15% association with job overload (95% CI, -8-38%) and 23% association with lack of institutional support (95% CI, 5-41%). While 32 (81%) residents increased attention to detail, only 2 (5%) increased their use of evidence-based medicine. CONCLUSIONS: Errors committed by emergency medicine residents often resulted in negative emotions, limited constructive system-based improvements, and inadequate disclosure. Negative perceptions of the training environment are associated with negative emotional responses.     

Aromatic residues affecting permeation and gating in dSlo BK channels

 Structural determinants of permeation in large unit conductance calcium-activated potassium channels (BK channels) were investigated. Y293 and F294 in the P-region of dSlo were substituted by tryptophans. Compared to wild-type channels, Y293W channels displayed reduced inward unitary currents while F294W channels exhibited normal inward current amplitudes but flickery kinetics. Both mutations produced changes in current/voltage relations under bi-ionic conditions. Sensitivity to block by external tetraethylammonium (TEA) was affected in both channels, and the voltage dependence of TEA block was increased in F294W channels. Both mutations also affected gating by shifting the half-maximal activation voltage of macroscopic conductance/voltage relations to more positive potentials, and eliminating a slow component of deactivation. The double mutant did not produce ionic currents. These data are consistent with a model in which Y293 contributes to a potassium-binding site close to the outer mouth of the dSlo pore, while F294 contributes to an energy barrier near this site. Received: 16 September 1997 / Received after revision: 20 November 1997 / Accepted: 21 November 1997     

Phagocytosis in the colonial ascidian Botryllus schlosseri

Phagocytosis by Botryllus schlosseri hemocytes in influenced by temperature, pH, concentration, and physicochemical properties of the test particles and requires Ca²⁺ or Mg²⁺ ions to occur. Phagocytes recognized glucosyl or mannosyl residues on the surface of yeast cells, and a respiratory burst is associated with phagocytosis, as indicated by increased superoxide production. Factors that enhance phagocytosis of yeast, sheep red blood cells, and latex beads and reduce the uptake of yeast and sheep erythrocytes are present in the plasma.     

Extraarticular synovial chondromatosis: review of epidemiology, imaging studies, microscopy and pathogenesis, with a report of an additional case in a child

A rare benign condition of uncertain etiology and pathogenesis, Synovial Chondromatosis (SC) is most often seen intraarticularly in adults but only a handful of cases have been reported extraarticularly in children. Symptoms and physical signs consist of pain, swelling, and osteoarthritic changes related to a mass effect. Here we discuss the case of a 9-year-old boy with documented SC of the knee and critically review the Epidemiology, Clinical Presentation, Gross Anatomy and Microscopic Histopathologic Features as well as the role of Imaging Studies in Diagnosis. In addition, this paper reviews Current Pathogenetic Concepts including the infrequent but distinct possibility of malignant transformation.     

Nitrosative stress in the bronchial mucosa of severe chronic obstructive pulmonary disease

BACKGROUND: Reactive nitrogen species, formed via the reaction of nitric oxide (NO) with superoxide anion and via (myelo)peroxidase-dependent oxidation of NO(2)(-), have potent proinflammatory and oxidizing actions. Reactive nitrogen species formation and nitrosative stress are potentially involved in chronic obstructive pulmonary disease (COPD) pathogenesis. OBJECTIVES: To investigate the expression of markers of nitrosative stress, including nitrotyrosine (NT), inducible NO synthase (iNOS), endothelial NO synthase (eNOS), myeloperoxidase (MPO), and xanthine oxidase (XO) in bronchial biopsies and bronchoalveolar lavage from patients with mild to severe stable COPD compared with control groups (smokers with normal lung function and nonsmokers). METHODS: The expression of NT, iNOS, eNOS, MPO and XO in the bronchial mucosa and bronchoalveolar lavage of patients was measured by using immunohistochemistry, Western blotting, and ELISA and correlated with the inflammatory cell profile. RESULTS: Patients with severe COPD in stable phase had higher numbers of NT(+) and MPO(+) cells in their bronchial submucosa compared with mild/moderate COPD, smokers with normal lung function, and nonsmokers (P < .01). iNOS(+) and eNOS(+) but not XO(+) cells were significantly increased in smokers with COPD or normal lung function compared with nonsmokers (P < .05 and P < .01, respectively). In patients with COPD, the number of MPO(+) cells was significantly correlated with the number of neutrophils (r = +0.61; P < .0025) in the bronchial submucosa. Furthermore, the number of NT(+) and MPO(+) cells was negatively correlated with postbronchodilator FEV(1). CONCLUSION: These data suggest that nitrosative stress, mainly mediated by MPO and neutrophilic inflammation, may contribute to the pathogenesis of severe COPD.     

Laboratory diagnosis of thrombophilic states: where do we stand?

Until recently the laboratory diagnosis of thrombophilia consisted on investigation of the plasmatic anticoagulant pathways and the search for dysfibrinogenemia and antiphospholipid antibodies/lupus anticoagulants. More recently, the laboratory investigation has been expanded by including activated protein C (APC) resistance, due or not to the presence of the factor V Leiden mutation; hyperprothrombinemia, due to the presence of the prothrombin mutation G20210A and hyperhomocysteinemia, due to impairment of the relevant metabolic pathway because of enzymatic and/or vitamin deficiency. Testing for thrombophilia may be useful for many reasons. First, the results of testing may provide valuable information to assess the risk of recurrence in the proband. Second, testing family members is useful for prophylactic and diagnostic purposes. Third, the identification of patients bearing combined defect helps to identify those at increased risk for thrombosis. Testing is recommended for patients with a past history of thrombosis and should be extended to their first-degree family members. Since most of the tests are not reliable during anticoagulation, it is preferable to postpone laboratory testing until after discontinuation of the treatment. Whenever possible testing should be performed by means of functional assays. DNA analysis is required for the prothrombin mutation G20210A. Laboratory diagnosis for antiphospholipid antibodies/lupus anticoagulant should be performed by a combination of tests including phospholipid-dependent clotting assays and solid phase anticardiolipin antibodies. Hyperhomocysteinemia may be assessed by high-pressure liquid chromatography methods, or by fluorescence polarization immunoassays.     

Comparative in vitro study on a ultra-high roughness and dense titanium coating

A new implant surface has been developed with the purpose of avoiding as much stress shielding as possible, and thus prolong the prosthesis lifespan. The aim of this study was to investigate the in vitro effect of this new ultra-high roughness and dense Titanium (Ti) surface (PG60, Ra = 74 microm) in comparison with medium (TI01, Ra = 18 microm) and high (TI60, Ra = 40 microm) roughness and open porous coatings; all the coatings were obtained by vacuum plasma spraying. MG63 osteoblast-like cells were seeded on the tested materials and polystyrene, as control, for 3 and 7 days. Cells proliferated on the material surfaces similarly to the control. Alkaline phosphatase activity had lower values for TI60 than TI01 (p < 0.0005) and PG60 (p < 0.005). Osteocalcin levels measured on TI60 were significantly (p < 0.0005) lower in comparison with TI01 and PG60 at 7 days. Procollagen-I synthesis reduced with increasing roughness and the lowest data was found for PG60. While at 3 days Transforming Growth Factor beta1 levels augmented with increasing roughness, at 7 days TI60, the high roughness surface, was significantly lower than PG60 (p < 0.005) and TI01 (p < 0.001). All tested materials showed significantly higher Interleukin-6 levels than those of polystyrene at both experimental times. Nitric Oxide activity on TI01 was significantly (p < 0.05) higher than on TI60 and polystyrene. In conclusion, the new ultra-high roughness and dense coating PG60 provided a good biological response, even though, at least in vitro, it behaved similarly to the coatings already used in orthopaedics.     

Comparative Disease Assessment: a multi-causal approach for estimating the burden of mortality

Journal of Public Health - The Comparative Risk Assessment (CRA) framework comprehensively evaluates the impact of exposure to risk factors on health populations using the counterfactual causal...