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Selected AbstractsProspective evaluation of angiogenic, hypoxic and EGFR-related biomarkers in recurrent glioblastoma multiforme treated with cetuximab, bevacizumab and irinotecanAPMIS, Issue 8 2010Benedikte Hasselbalch Hasselbalch B, Eriksen JG, Broholm H, Christensen IJ, Grunnet K, Horsman MR, Poulsen HS, Stockhausen M-T, Lassen U. Prospective evaluation of angiogenic, hypoxic and EGFR-related biomarkers in recurrent glioblastoma multiforme treated with cetuximab, bevacizumab and irinotecan. APMIS 2010; 118: 585,94. Several recent studies have demonstrated a beneficial effect of anti-angiogenic treatment with the vascular endothelial growth factor-neutralizing antibody bevacizumab in recurrent high-grade glioma. In the current study, immunohistochemical evaluation of biomarkers involved in angiogenesis, hypoxia and mediators of the epidermal growth factor receptor (EGFR) pathway were investigated. Tumor tissue was obtained from a previous phase II study, treating recurrent primary glioblastoma multiforme (GBM) patients with the EGFR inhibitor cetuximab in combination with bevacizumab and irinotecan. Of the 37 patients with available tumor tissue, 29 were evaluable for response. We concurrently performed immunohistochemical stainings on tumor tissue from 21 GBM patients treated with bevacizumab and irinotecan. We found a tendency of correlation between the hypoxia-related markers, indicating that they share the same regulatory mechanisms. None of the EGFR-related biomarkers showed any significant correlations with each other. None of the biomarkers tested alone or in combination could identify a patient population likely to benefit from bevacizumab and irinotecan, with or without the addition of cetuximab. There is still an urgent need for one or more reliable and reproducible biomarkers able to predict the efficacy of anti-angiogenic therapy. [source] Characteristics and Referral of Emergency Department Patients with Elevated Blood PressureACADEMIC EMERGENCY MEDICINE, Issue 9 2007Brigitte M. Baumann MD, MSCE Objectives: To assess the prevalence, characteristics, and referral to health care of emergency department (ED) patients with elevated blood pressure (BP) and to compare those without a history of hypertension (HTN) with suboptimally controlled, known-hypertensive patients. Methods: A prospective, observational study was conducted in non,critically ill adults with a triage systolic blood pressure (sBP) of ,140 or with a diastolic blood pressure (dBP) of ,90 mmHg. Two additional measurements were obtained, and a standardized questionnaire recorded demographics, medical history, and ED staff referrals. Results: Of 1,719 nonpregnant adults, 991 agreed to participate, of whom 455 had elevated triage BP values. Using the mean of three measurements, 305 (67%) had an sBP of ,140 or a dBP of ,90 mm Hg (mean sBP = 157 and mean dBP = 89 mm Hg). Subjects with no prior history of HTN (n = 105) were predominantly male, younger, and more likely to smoke and consume alcohol than were known-hypertensive patients (n = 200). Three quarters of all subjects had access to primary health care; however, time elapsed since the last BP assessment was greater (155 vs. 53 d, p = 0.03) in subjects with no previous history. These subjects were also less likely to be informed of their elevated BP (33% vs. 50%, p = 0.02) or to be instructed by ED staff to obtain a repeat measurement (13% vs. 31%, p = 0.001). Conclusions: Of ED patients with elevated BP, one third had no prior history, and the remainder were suboptimally controlled hypertensive patients. Both groups were inadequately informed of their elevated BPs, and the group with no prior history of HTN, the population likely to obtain the greatest health benefit, had the lowest referral rate. [source] Can intra-specific genetic variation in arbuscular mycorrhizal fungi (Glomus etunicatum) affect a mesophyll-feeding herbivore (Tupiocoris notatus Distant)?ECOLOGICAL ENTOMOLOGY, Issue 4 2007STUART C. WOOLEY Abstract 1.,Arbuscular mycorrhizal fungal (AMF) infection can have negative, positive or neutral effects on insect herbivore populations, but patterns are difficult to predict. 2.,Intra-specific genetic variation in nutrient uptake ability between fungal isolates may also have indirect effects on insect herbivores due to changes in plant quality. In preliminary studies mirid (Tupiocoris notatus) populations were significantly reduced on tobacco (Nicotiana rustica) colonised by AMF but it was unknown if same-species fungal isolates differed in their effect. 3.,An experiment was performed as a first test of the effect of intra-specific genetic variation in the mycorrhizal fungus Glomus etunicatum on mirid nymphal population structure, dynamics, and growth rate. 4.,Mirid nymphal populations were lower on mycorrhizal fungal-infected plants. Population size, however, did not differ between the mycorrhizal isolates. While no statistical difference in population between isolates was found, one isolate consistently had 1.7,2.4 times lower mirid populations compared with the controls, indicating that the magnitude of effect is different between mycorrhizal isolates. 5.,The significantly negative effect of AMF on mirid populations likely resulted from AMF-induced changes in plant quality (e.g. increased defence). This study lends further support to recent demonstrations that below-ground symbionts significantly influence above-ground processes. In addition, mycorrhizal fungi can affect insect population structure, which may have consequences for future herbivory. [source] Risk factors for coronary heart disease in 55- and 35-year-old men and women in Sweden and EstoniaJOURNAL OF INTERNAL MEDICINE, Issue 6 2002J. Johansson Abstract., Johansson J, Viigimaa M, Jensen-Urstad M, Krakau I I, Hansson L-O (Karolinska Hospital, Stockholm, Sweden, Tartu University Hospital, Tartu, Estonia). Risk factors for coronary heart disease in 55- and 35-year-old men and women in Sweden and Estonia. J Intern Med 2002; 252:551,560. Objective., To illustrate the geographical West-to-East division of coronary heart disease (CHD) by comparing a population from Sweden, that represents a Western country to a population from Estonia, that represents an Eastern country. Estonia has an approximately 2,4-fold higher CHD prevalence for 55-year-old women and men, respectively, than Sweden. Design., Randomized screening of 35- and 55-year-old men and women in Sollentuna county, Sweden and Tartu county, Estonia. Eight hundred subjects, 100 from each cohort, were invited to participate in the study, 272 Swedes and 277 Estonians participated. Setting., Preventive cardiology, administered by a primary health care centre at the Karolinska Hospital, Sweden and a cardiology centre at Tartu University Hospital, Estonia. Main outcome measures., The CHD risk factors (smoking, blood pressure, concentrations of lipoproteins, fibrinogen, and glucose) and certain environmental factors and attitudes related to CHD risk by questionnaires (fat-type and alcohol ingestion, self-assessed rating of CHD susceptibility). Results., Of the 55-year-old men, 57% smoked in Estonia and 20% smoked in Sweden. Similar, although less pronounced differences showing higher smoking prevalence, were seen for 35-year-old Estonian men and women, whilst for 55-year-old women, less than 20% smoked in either country. Estonian 55-year-old women had lower HDL cholesterol and higher LDL cholesterol serum concentrations than Swedish 55-year-old women. Estonians reportedly ate food containing more saturated fats than Swedes, as indicated by the scale-score questionnaire. Estonians, relative to Swedes, rated their chance of developing CHD higher, and paradoxically, Estonians did to a much lesser degree believe that life style influences the risk of developing CHD. Conclusions., Elevated smoking prevalence is a striking difference between the Estonian and Swedish populations likely to explain the much higher CHD prevalence in Estonian men. The lower HDL cholesterol and higher LDL cholesterol in Estonian 55-year-old women may explain the higher CHD prevalence in Estonian women. Furthermore, the SWESTONIA CHD study (i.e. comparison between Sweden and Estonia) shows several environmental differences between the countries populations related to fat content in food, alcohol drinking patterns, and views on CHD risk and the importance of lifestyle intervention, that could contribute to the higher CHD prevalence in Estonia. [source] Acute pancreatitis in dogsJOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue 4 2003Jennifer L. Holm DVM Abstract Objective: To summarize current information regarding severity assessment, diagnostic imaging, and treatment of human and canine acute pancreatitis (AP). Human-based studies: In humans, scoring systems, advanced imaging methods, and serum markers are used to assess the severity of disease, which allows for optimization of patient management. The extent of pancreatic necrosis and the presence of infected pancreatic necrosis are the most important factors determining the development of multiple organ failure (MOF) and subsequent mortality. Considerable research efforts have focused on the development of inexpensive, easy, and reliable laboratory markers to assess disease severity as early as possible in the course of the disease. The use of prophylactic antibiotics, enteral nutrition, and surgery have been shown to be beneficial in certain patient populations. Veterinary-based studies: The majority of what is currently known about naturally occurring canine AP has been derived from retrospective evaluations. The identification and development of inexpensive and reliable detection kits of key laboratory markers in dogs with AP could dramatically improve our ability to prognosticate and identify patient populations likely to benefit from treatment interventions. Treatment remains largely supportive and future studies evaluating the efficacy of surgery, nutritional support and other treatment modalities are warranted. Data sources: Current human and veterinary literature. Conclusions: Pancreatitis can lead to a life-threatening severe systemic inflammatory condition, resulting in MOF and death in both humans and dogs. Given the similarities in the pathophysiology of AP in both humans and dogs, novel concepts used to assess severity and treat people with AP may be applicable to dogs. [source] Treatment of CML in pediatric patients: Should imatinib mesylate (STI-571, Gleevec) or allogeneic hematopoietic cell transplant be front-line therapy?PEDIATRIC BLOOD & CANCER, Issue 5 2004Michael A. Pulsipher MD Abstract Background Long-term survival of pediatric patients with chronic myelogenous leukemia (CML) receiving myeloablative hematopoietic stem cell transplantation from fully-matched related and unrelated donors has been reported between 60 and 75%, but is associated with significant morbidity. Imatinib mesylate (STI-571, Gleevec) and reduced intensity conditioning stem cell transplantation (RIC) are two promising new tools that offer potential for decreasing therapy associated morbidity for patients with CML. Results Large trials have shown significant responses in chronic phase patients treated with imatinib and reasonable but short-lived responses in advanced phase CML. Data from adult studies is beginning to define populations likely to progress or have prolonged responses to imatinib, and some adult treatment paradigms are moving toward reserving transplantation until patients are at risk of failure with imatinib. Early trials of RIC transplantation in CML show decreased transplant related morbidity with efficacy similar to conventional transplantation, but the approach has yet to be verified in phase III studies. Data in pediatric patients with imatinib and RIC transplantation is limited. Conclusions Studies with imatinib are underway in pediatrics, but whether pediatric dosing schemes will lead to outcomes similar to adults is unknown. Because HLA-matched myeloablative transplantation offers a high rate of cure in the pediatric population, clinical studies assessing the role of imatinib mesylate and RIC transplantation should be planned carefully in order to avoid sub-optimal outcomes. © 2004 Wiley-Liss, Inc. [source] |