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Selected AbstractsExpert Review of the Evidence Base for Prevention of Travelers' DiarrheaJOURNAL OF TRAVEL MEDICINE, Issue 3 2009Herbert L. DuPont MD The most frequent illness among persons traveling from developed to developing countries is travelers' diarrhea. Travelers to high-risk regions traditionally have been educated to exercise care in food and beverage selection. Innovative research is needed to identify ways to motivate people to exercise this care and to determine its value. Chemoprophylaxis can be recommended for certain groups while monitoring for safety, drug resistance, and efficacy against all forms of bacterial diarrhea. Research to evaluate the value of immunoprophylaxis is recommended. In the following document, the authors used an evidence base when available to determine strength and quality of evidence and when data were lacking, the panel experts provided consensus opinion. [source] Expressing the Middle English ILITERATURE COMPASS (ELECTRONIC), Issue 4 2009Isabel Davis This article surveys the rich ways in which Middle English authors used the word I, considering what it can tell us about the medieval conceptualizations of subjectivity. It argues against the idea of a sharp break between medieval and early modern accounts of selfhood, and in favour of a more sensitive understanding of the genres of medieval first-person writing, suggesting reasons why those genres don't easily correspond to categories of modern life-writing. This article considers allegory, the rhetorical device of the persona, and spiritual and allegorical ,autobiographies' in Middle English in order to arrive at an account of how medieval authors revised the influential accounts of subjectivity that they inherited from late Antique writers like Boethius and St Augustine and dramatized the subject as a site of competing psychological faculties which were in constant dialogue and distress. This article gathers its evidence from, and offers specific readings of a range of Middle English literature by Geoffrey Chaucer, John Gower, Thomas Usk, Thomas Hoccleve, Osbern Bokenham, Margery Kempe, Julian of Norwich, the York dramatist and, of course, Anon. [source] Differential Roles of CD36, ICAM-1, and P-selectin in Plasmodium falciparum Cytoadherence In VivoMICROCIRCULATION, Issue 6 2007Bryan G. Yipp ABSTRACT Cytoadherence of Plasmodium falciparum -infected red blood cells (IRBCs) on human microvascular endothelium is mediated by synergistic adhesive interactions with different adhesion molecules in vitro. Here, the authors used a unique human/severe combined immunodeficient (SCID) mouse chimeric model to directly visualize IRBC,endothelial interactions in an intact human microvasculature in vivo. Stimulation of human skin grafts with 100 ng TNF-, for 4 h led to a dramatic reduction in the distance rolled by IRBCs before arrest, so that the majority of IRBCs adhered directly to the endothelium with a 1.8-fold increase in the number of adherent cells. The decrease in rolling distance and increase in adhesion could be reversed by anti-ICAM-1. More importantly, the effect of TNF-, could be seen only in the presence of CD36. A further increase in adhesion by 4.9-fold was observed after 24 h of TNF-, stimulation. The increase could be reversed by anti-ICAM-1, but not anti-VCAM-1. In histamine-stimulated grafts, the rolling flux fraction and adhesion increased by 2.8- and 1.6-fold, respectively. The increases were attributable to P-selectin as an inhibitory anti-P-selectin antibody abrogated both the increased rolling flux fraction and firm adhesion. These findings indicate that in addition to CD36, ICAM-1, and P-selectin are major contributors to the dynamic process of IRBC adhesion by different mechanisms in vivo. [source] Accurate calculation of the density of proteinsACTA CRYSTALLOGRAPHICA SECTION D, Issue 7 2000Michael L. Quillin On the basis of theoretical calculations, Andersson & Hovmöller have recently suggested that the long-established value of 1.35,g,cm,3 for the mean density of proteins should be revised to 1.22,g,cm,3[Andersson & Hovmller (2000), Acta Cryst. D56, 789790]. To substantiate their assertion, these authors used the Voronoi algorithm to calculate the mean atomic volume for 30 representative protein structures. The Voronoi procedure requires that atoms of interest be bounded on all sides by other atoms. Volume calculations for surface atoms that are not surrounded or are only sparsely surrounded by other atoms either are not possible or may be unreliable. In an attempt to circumvent this problem, Andersson & Hovmöller rejected atoms with calculated volumes that were indeterminate or were greater than 50,Å3. In the present study, it is shown that this criterion is not sufficiently restrictive to ensure accurate volume determinations. When only strictly buried atoms are included in the volume calculations using the Voronoi algorithm, the mean density is found to be 1.47 ± 0.05,g,cm,3. In addition, an alternate procedure based on the Connolly algorithm that permits all protein atoms to be included in volume calculations gives 1.43 ± 0.03,g,cm,3 for the mean density of the same set of proteins. The latter two calculated values are mutually consistent and are in better agreement with the experimental value. [source] Routine perioperative chemotherapy instillation with initial bladder tumor resectionCANCER, Issue 5 2009A reconsideration of economic benefits Abstract BACKGROUND: Level-1 evidence has demonstrated decreased recurrence of low-grade bladder tumors when initial transurethral resection (TUR) is followed by perioperative instillation (PI) of chemotherapy. A meta-analysis determined that the number needed to treat (NNT) was 8.5 patients to prevent 1 recurrence. No benefit was demonstrated for tumors classified as T0, tumor in situ, or T2; thus, patients with those tumors were excluded from the analysis, which potentially may have resulted in underestimating the true NNT. Economic benefits were suggested, but cost calculations were not presented. The objectives of the current analysis were to recalculate the NNT considering patients who previously were excluded and to examine the economic implications based on various management alternatives for tumor recurrence. METHODS: For each study that was included in the current meta-analysis, the number of patients excluded because of ,inappropriate' pathology results was determined. A potentially more accurate NNT was calculated, and pertinent Medicare reimbursements were obtained to estimate costs. RESULTS: The added cost for 8.5 patients who underwent inpatient TUR to receive PI was $1711. Inpatient TUR ($7025) was extremely costly compared with hospital outpatient TUR ($2666), ambulatory surgery center TUR ($2113), and physician office fulguration ($1167). Although the inclusion of patients who previously were excluded resulted in a recalculated NNT of 9.6 patients, the authors used a more conservative NNT if 8.5 patients to estimate the economic impact of the ,best-case scenario.' CONCLUSIONS: Routine PI significantly lowered the overall cost if recurrences were managed in the inpatient setting, but these benefits were offset mostly or completely by outpatient management in the United States. Thus, the authors concluded that the decision to use routine PI of chemotherapy should be based on clinical effects and not on presumed economic benefits. Cancer 2009. © 2009 American Cancer Society. [source] Expression of the nuclear export protein chromosomal region maintenance/exportin 1/Xpo1 is a prognostic factor in human ovarian cancerCANCER, Issue 8 2008Aurelia Noske MD Abstract BACKGROUND The human nuclear export protein chromosomal region maintenance/exportin 1/Xpo1 (CRM1) mediates the nuclear export of proteins and messenger RNAs and, thus, is an important regulator of subcellular distribution of key molecules. Whereas cell-biologic studies have suggested a fundamental role for CRM1 in the regulation of mitosis, the expression of this protein in human tumor tissue has not been investigated to date. METHODS In this study, the expression of CRM1 was analyzed in a cohort of 88 ovarian tumors and 12 ovarian cell lines for the first time to the authors' knowledge. RESULTS Immunohistochemistry revealed increased nuclear (52.7%) and cytoplasmic (56.8%) expression of CRM1 in 74 carcinomas compared with the expression revealed in borderline tumors and benign lesions. Similarly, CRM1 expression was increased in ovarian cancer cell lines compared with human ovarian surface epithelial cells. Cytoplasmic CRM1 expression was related significantly to advanced tumor stage (P = .043), poorly differentiated carcinomas (P = .011), and higher mitotic rate (P = .008). Nuclear CRM1 was associated significantly with cyclooxygenase-2 (COX-2) expression (P = .002) and poor overall survival (P = .01). Because it was demonstrated previously that blocking of CRM1 by leptomycin B (LMB) contributes to the inhibition of nuclear export, the authors used a set of mechanistic assays to study the effects of CRM1 inhibition in cancer cells. Treatment of OVCAR-3 cells with LMB revealed a significant reduction of cell proliferation and increased apoptosis as well as suppressed interleukin-1,-induced COX-2 expression. CONCLUSIONS The current results indicated that CRM1 is expressed in a subpopulation of ovarian carcinomas with aggressive behavior and is related to poor patient outcome. A correlation also was demonstrated between CRM1 and COX-2 expression in ovarian cancer tissue. Furthermore, the treatment of ovarian cancer cells with LMB revealed a reduction in COX-2 expression. Therefore, the authors suggest that CRM1 may be an interesting biomarker for the assessment of patient prognosis and a molecular target for anticancer treatment. Cancer 2008. © 2008 American Cancer Society. [source] Factors that influence physicians' detection of distress in patients with cancer,CANCER, Issue 2 2005Can a communication skills training program improve physicians' detection? Abstract BACKGROUND No study to date has assessed the impact of skills acquisition after a communication skills training program on physicians' ability to detect distress in patients with cancer. METHODS First, the authors used a randomized design to assess the impact, on physicians' ability to detect patients' distress, of a 1-hour theoretical information course followed by 2 communication skills training programs: a 2.5-day basic training program and the same training program consolidated by 6 3-hour consolidation workshops. Then, theinvestigate contextual, patient, and communication variables or factors associated with physicians' detection of patients' distress were investigated. After they attended the basic communication skills training program, physicians were assigned randomly to consolidation workshops or to a waiting list. Interviews with a cancer patient were recorded before training, after consolidation workshops for the group that attended consolidation workshops, and , 5 months after basic training for the group that attended basic training without the consolidation workshops. Patient distress was recorded with the Hospital Anxiety and Depression Scale before the interviews. Physicians rated their patients' distress on a visual analog scale after the interviews. Physicians' ability to detect patients' distress was measured through computing differences between physicians' ratings of patients' distress and patients' self-reported distress. Communication skills were analyzed according to the Cancer Research Campaign Workshop Evaluation Manual. RESULTS Fifty-eight physicians were evaluable. Repeated-measures analysis of variance showed no statistically significant changes over time and between groups in physicians' ability to assess patient distress. Mixed-effects modeling showed that physicians' detection of patients' distress was associated negatively with patients' educational level (P = 0.042) and with patients' self-reported distress (P < 0.000). Mixed-effects modeling also showed that physicians' detection of patient distress was associated positively with physicians breaking bad news (P = 0.022) and using assessment skills (P = 0.015) and supportive skills (P = 0.045). CONCLUSIONS Contrary to what was expected, no change was observed in physicians' ability to detect distress in patients with cancer after a communication skills training programs, regardless of whether physicians attended the basic training program or the basic training program followed by the consolidation workshops. The results indicated a need for further improvements in physicians' detection skills through specific training modules, including theoretical information about factors that interfere with physicians' detection and through role-playing exercises that focus on assessment and supportive skills that facilitate detection. Cancer 2005. © 2005 American Cancer Society. [source] High-dose 131I-metaiodobenzylguanidine therapy for 12 patients with malignant pheochromocytomaCANCER, Issue 2 2003Brian Rose M.D. Abstract BACKGROUND 131I-Metaiodobenzylguanidine (131I-MIBG) can be used systemically to treat malignant pheochromocytoma. To improve outcome, the authors used higher levels of activity of 131I-MIBG than previously reported. The authors reported the response rates and toxicity levels in patients with malignant pheochromocytoma or paraganglioma who were treated with high-dose 131I-MIBG. METHODS Following debulking surgery and stem cell harvest, 12 patients with malignant pheochromocytoma or paraganglioma were treated with 131I-MIBG. Five had received previous external beam radiation and/or chemotherapy. The median single treatment dose was 800 mCi (37 gigabecquerels; range, 386,866 mCi) or 11.5 mCi/kg (range, 5.6,18.3 mCi/kg). The median cumulative dose was 1015 mCi (range, 386,1690 mCi). RESULTS Three patients had a complete response, two of whom had soft tissue and skeletal metastases. Their median follow-up was 45 months (range, 23,101 months). Seven patients had a partial response (PR), with a median follow-up 43 months (range, 6,47 months). Two patients without a response died with progressive disease (PD) and 2 patients with an initial PR died of PD at 13 and 11 months, respectively. Grade 3 thrombocytopenia occurred after 79% (15 of 19) of treatments had been administered. Grade 3 and 4 neutropenia followed 53% (10 of 19) and 19% (4 of 19) of treatments, respectively. One patient required stem cell infusion, and one developed primary ovarian failure. CONCLUSIONS The single and cumulative doses of 131I-MIBG were approximately 2,3.5 times higher than those used at other centers. Unlike previous reports, two patients with both skeletal and soft tissue metastases had a complete response. Hematologic toxicity was significant but tolerable. High-dose 131I-MIBG may lead to long-term survival in patients with malignant pheochromocytoma. Cancer 2003;98:239,48. © 2003 American Cancer Society. DOI 10.1002/cncr.11518 [source] | ||||||||||