Inhaled Methoxyflurane Provides Greater Analgesia and Faster Onset of Action Versus Standard Analgesia in Patients With Trauma Pain: InMEDIATE: A Randomized Controlled Trial in Emergency Departments

STUDY OBJECTIVE: The objective of the InMEDIATE study was to evaluate the change in intensity of traumatic pain over the first 20 min in adult patients treated with methoxyflurane versus standard analgesic treatment in Spain. This the first randomized, active-controlled, multicenter trial of methoxyflurane in the emergency setting in Europe. METHODS: This was a randomized, controlled study that enrolled adult patients with acute moderate to severe (score >/=4 on the 11-point Numeric Rating Scale) trauma-associated pain in 14 Spanish emergency departments. Patients were randomized 1:1 to methoxyflurane (up to 2x3 mL) or standard analgesic treatment. Coprimary endpoints were the change from baseline in Numeric Rating Scale pain intensity score during the first 20 minutes of treatment and time to first pain relief. RESULTS: Three hundred five patients were randomized (methoxyflurane 156; standard analgesic treatment 149). Most patients in the standard analgesic treatment group (70%) received intravenous first-step analgesics and 9.4% of patients were treated with opioids. Mean decrease from baseline in Numeric Rating Scale pain intensity score was greater for methoxyflurane than standard analgesic treatment at all points, with a significant treatment difference overall up to 20 minutes (repeated-measures model 2.47 versus 1.39; treatment difference 1.00; 95% confidence interval 0.84 to 1.32). Median time to first pain relief was significantly shorter for methoxyflurane than standard analgesic treatment (3 versus 10 minutes). Methoxyflurane achieved better patient and clinician ratings for pain control and comfort of treatment than standard analgesic treatment and exceeded patient and clinician expectations of treatment in, respectively, 77% and 72% of cases compared with 38% and 19% for standard analgesic treatment. CONCLUSION: These results support consideration of methoxyflurane as a nonnarcotic, easy-to-administer, rapid-acting, first-line alternative to currently available analgesic treatments for trauma pain

Relationship between morphological features and kinetic patterns of enhancement of the dynamic breast magnetic resonance imaging and clinico-pathological and biological factors in invasive breast cancer

<p>Abstract</p> <p>Background</p> <p>To investigate the relationship between the magnetic resonance imaging (MRI) features of breast cancer and its clinicopathological and biological factors.</p> <p>Methods</p> <p>Dynamic MRI parameters of 68 invasive breast carcinomas were investigated. We also analyzed microvessel density (MVD), estrogen and progesterone receptor status, and expression of p53, HER2, ki67, VEGFR-1 and 2.</p> <p>Results</p> <p>Homogeneous enhancement was significantly associated with smaller tumor size (T1: < 2 cm) (p = 0.015). Tumors with irregular or spiculated margins had a significantly higher MVD than tumors with smooth margins (p = 0.038). Tumors showing a maximum enhancement peak at two minutes, or longer, after injecting the contrast, had a significantly higher MVD count than those which reached this point sooner (p = 0.012). The percentage of tumors with vascular invasion or high mitotic index was significantly higher among those showing a low percentage (≤ 150%) of maximum enhancement before two minutes than among those ones showing a high percentage (>150%) of enhancement rate (p = 0.016 and p = 0.03, respectively). However, there was a significant and positive association between the mitotic index and the peak of maximum intensity (p = 0.036). Peritumor inflammation was significantly associated with washout curve type III (p = 0.042).</p> <p>Conclusions</p> <p>Variations in the early phase of dynamic MRI seem to be associated with parameters indicatives of tumor aggressiveness in breast cancer.</p

Definitive characterization of CA 19-9 in resectable pancreatic cancer using a reference set of serum and plasma specimens

The validation of candidate biomarkers often is hampered by the lack of a reliable means of assessing and comparing performance. We present here a reference set of serum and plasma samples to facilitate the validation of biomarkers for resectable pancreatic cancer. The reference set includes a large cohort of stage I-II pancreatic cancer patients, recruited from 5 different institutions, and relevant control groups. We characterized the performance of the current best serological biomarker for pancreatic cancer, CA 19-9, using plasma samples from the reference set to provide a benchmark for future biomarker studies and to further our knowledge of CA 19-9 in early-stage pancreatic cancer and the control groups. CA 19-9 distinguished pancreatic cancers from the healthy and chronic pancreatitis groups with an average sensitivity and specificity of 70-74%, similar to previous studies using all stages of pancreatic cancer. Chronic pancreatitis patients did not show CA 19-9 elevations, but patients with benign biliary obstruction had elevations nearly as high as the cancer patients. We gained additional information about the biomarker by comparing two distinct assays. The two CA 9-9 assays agreed well in overall performance but diverged in measurements of individual samples, potentially due to subtle differences in antibody specificity as revealed by glycan array analysis. Thus, the reference set promises be a valuable resource for biomarker validation and comparison, and the CA 19-9 data presented here will be useful for benchmarking and for exploring relationships to CA 19-9

Equity-liability accounting debate in worker co-operative entities members' shares

It is generally accepted that common high quality financial information standards are essential in a global economy. The comparability of financial information is necessary in order to facilitate the decision-making process with regard to capital flows between different countries. This complex harmonization process focuses attention on investor-owned business. Nevertheless, this process cannot progress without an appropriate analysis of the nature of other types of entity. General criteria may be insufficient or inadequate when applied to entities, such as co-operatives, in which there is a difference from the basic ownership parameters of a company. International accounting standards setters are involved in a project that reconsiders the principles that should determine the distinction between equity and liabilities. Many of the specific characteristics of co-operatives have a bearing on the recognition and measurement of their equity in the balance sheet. The aim of this paper is to contribute to this debate by analysing the features of co-operatives that need to be visualized and better understood in order to obtain an appropriate solution via the accounting harmonization process for co-operatives. We analyse the possible consequences for co-operative member shares accounting of the different approaches studied by international accounting standards setters. We highlight the impact of some of the tentative decisions adopted in the IASB and FASB joint project in the case of worker co-operative members' shares

Tissue-Type Plasminogen Activator (tPA) Content in Colorectal Cancer and in Surrounding Mucosa: Relationship with Clinicopathologic Parameters and Prognostic Significance

The aim of this study was to evaluate the cytosolic tissue-type plasminogen activator (tPA) content in colorectal cancer, its possible relationship with the clinicopathologic parameters of tumors, and its prognostic significance. We have therefore examined by immunoenzymatic assay the cytosolic tPA content in tumors and paired surrounding normal mucosa samples from 162 colorectal cancer patients. Cytosolic tPA levels were significantly higher in surrounding normal mucosa samples than in neoplastic tissues (4.01±5.07 vs 2.63±5.82 ng/mg protein; p&lt;0.0001). By contrast, no significant correlation was found between tPA content and clinicopathologic tumor parameters such as location, Dukes’ stage, histologic grade, and DNA content or S-phase fraction. However, the results indicated that a high cytosolic tPA content (&gt;0.75 ng/mg protein) in tumors predicted for a shorter relapse-free and overall survival (both p&lt;0.05) in 123 resectable colorectal cancer patients who were prospectively evaluated during a mean follow-up period of 32.2 months. This suggests that tPA may give additional information to that provided by other biochemical markers currently used in colorectal cancer. </jats:p

c-erbB-2 Oncoprotein Content in Gastric Cancer and in Adjacent Mucosa

The aim of this study was to evaluate, by means of an immunoenzymatic assay, the membranous and cytosolic c-erbB-2 oncoprotein contents in primary tumors and in adjacent mucosa from gastric cancer patients. Fifty-two patients with primary gastric adenocarcinomas were enrolled in this prospective study. c-erbB-2 protein levels were significantly higher in membranous than in cytosolic samples, both in neoplastic tissues (median: 3602 vs 525 NHU/mg protein; p&lt;0.0001) and in adjacent mucosa samples (median: 3174 vs 509 NHU/mg protein; p&lt;0.0001). Nevertheless, there was a significant positive relation between membranous and cytosolic c-erbB-2 protein contents in both neoplastic tissue (p&lt;0.001) and adjacent mucosa (p&lt;0.001) samples. There was no significant difference in the membranous c-erbB-2 protein content between neoplastic tissues and adjacent mucosa samples. However, the cytosolic c-erbB-2 content was significantly higher in neoplastic tissues than in adjacent mucosa (p&lt;0.05). Finally, the results did not show any significant correlations of these oncoprotein contents with patient characteristics, clinicopathologic parameters and overall survival of the study population. </jats:p

Clinical Significance of Epidermal Growth Factor Receptor Content in Gastric Cancer

The objective of this work was to evaluate the epidermal growth factor receptor (EGFR) content in gastric cancer, its possible relationship with clinicopathological parameters of tumors and its prognostic significance. Membranous EGFR levels were examined by radioligand binding assays in 110 patients with gastric cancer. The mean follow-up period was 30.7 months. EGFR levels of tumors ranged widely, from 0.3 to 510 fmol/mg protein. EGFR levels were significantly higher (p&lt;0.0005) in neoplastic tissue than in paired adjacent mucosa samples (median) (n= 84; 8.7 vs. 3.9 fmol/mg protein). Intratumoral EGFR levels were significantly correlated with tumor stage (p&lt;0.05), and were higher in patients with stage III tumors (median) (7.6, 6.4, 12.3 and 7.5 fmol/mg protein for stages I, II, III and IV, respectively). In addition, the tumor/mucosa ratios of the EGFR content were significantly higher (p&lt;0.05) in patients with stage III tumors (1, 1.8, 3.9, and 0.92, respectively). Although there was no significant relationship between EGFR levels of tumors and overall survival, the results suggest a role for EGFR in tumor progression of gastric cancer. </jats:p