Cardiovascular, respiratory, gastrointestinal and behavioral effects of intravenous lidocaine in healthy, conscious horses and evaluation of the relationship with lidocaine and monoethylglycinexylidide serum concentrations

This study aimed to evaluate the relationship between the serum concentrations of lidocaine/ monoethylglycinexylidide (MEGX) and their effects on several systems in horses. Five healthy, conscious horses received a two-hour placebo intravenous infusion followed by a two-hour lidocaine infusion (bolus of 1.3 mg/kg over ten minutes followed by a continuous rate infusion of 0.05 mg/kg/min). Lidocaine and MEGX serum concentrations were sampled every ten to fifteen minutes during the experiment, and the presence of muscle fasciculations and loss of balance as well as the respiratory, digestive and cardiovascular systems of the five horses were evaluated by means of different non-invasive methods. During the lidocaine infusion, the mean (f SD) lidocaine and MEGX concentrations were respectively 768.88 +/- 93.32ng/ml and 163.08 +/- 108.98 ng/ml. The infusion of lidocaine significantly influenced the presence of fasciculations, caused a statistically but non-clinically significant decrease of systolic and diastolic blood pressures, which were both correlated with lidocaine and MEGX serum concentrations, and it increased the duodenal contractions frequency, which was correlated with the serum lidocaine concentration. In this study, mild hypotensive and prokinetic effects of short-term lidocaine infusion were observed

Global and regional estimates of cancer mortality and incidence by site: II. results for the global burden of disease 2000

BACKGROUND: Mortality estimates alone are not sufficient to understand the true magnitude of cancer burden. We present the detailed estimates of mortality and incidence by site as the basis for the future estimation of cancer burden for the Global Burden of Disease 2000 study. METHODS: Age- and sex- specific mortality envelope for all malignancies by region was derived from the analysis of country life-tables and cause of death. We estimated the site-specific cancer mortality distributions from vital records and cancer survival model. The regional cancer mortality by site is estimated by disaggregating the regional cancer mortality envelope based on the mortality distribution. Estimated incidence-to-mortality rate ratios were used to back calculate the final cancer incidence estimates by site. RESULTS: In 2000, cancer accounted for over 7 million deaths (13% of total mortality) and there were more than 10 million new cancer cases world wide in 2000. More than 60% of cancer deaths and approximately half of new cases occurred in developing regions. Lung cancer was the most common cancers in the world, followed by cancers of stomach, liver, colon and rectum, and breast. There was a significant variations in the distribution of site-specific cancer mortality and incidence by region. CONCLUSIONS: Despite a regional variation, the most common cancers are potentially preventable. Cancer burden estimation by taking into account both mortality and morbidity is an essential step to set research priorities and policy formulation. Also it can used for setting priorities when combined with data on costs of interventions against cancers

Alterations in Mesenteric Lymph Node T Cell Phenotype and Cytokine Secretion are Associated with Changes in Thymocyte Phenotype after LP-BM5 Retrovirus Infection

In this study, mouse MLN cells and thymocytes from advanced stages of LP-BM5 retrovirus infection were studied. A decrease in the percentage of IL-7+ cells and an increase in the percentage of IL-16+ cells in the MLN indicated that secretion of these cytokines was also altered after LP-BM5 infection. The percentage of MLN T cells expressing IL-7 receptors was significantly reduced, while the percentage of MLN T cells expressing TNFR-p75 and of B cells expressing TNFR-p55 increased. Simultaneous analysis of surface markers and cytokine secretion was done in an attempt to understand whether the deregulation of IFN-Υ secretion could be ascribed to a defined cell phenotype, concluding that all T cell subsets studied increased IFN-Υ secretion after retrovirus infection. Finally, thymocyte phenotype was further analyzed trying to correlate changes in thymocyte phenotype with MLN cell phenotype. The results indicated that the increase in single positive either CD4+CD8- or CD4- CD8+ cells was due to accumulation of both immature (CD3- ) and mature (CD3+) single positive thymocytes. Moreover, single positive mature thymocytes presented a phenotype similar to the phenotype previously seen on MLN T cells. In summary, we can conclude that LP-BM5 uses the immune system to reach the thymus where it interferes with the generation of functionally mature T cells, favoring the development of T cells with an abnormal phenotype. These new T cells are activated to secrete several cytokines that in turn will favor retrovirus replication and inhibit any attempt of the immune system to control infection

Cost-Effectiveness of Pain Management Strategies in Advanced Cancer

Objectives Uncontrolled pain in advanced cancer is a common problem and has significant impact on individuals’ quality of life and use of healthcare resources. Interventions to help manage pain at the end of life are available, but there is limited economic evidence to support their wider implementation. We conducted a case study economic evaluation of two pain self-management interventions (PainCheck and Tackling Cancer Pain Toolkit [TCPT]) compared with usual care. Methods We generated a decision-analytic model to facilitate the evaluation. This modelled the survival of individuals at the end of life as they moved through pain severity categories. Intervention effectiveness was based on published meta-analyses results. The evaluation was conducted from the perspective of the U.K. health service provider and reported cost per quality-adjusted life-year (QALY). Results PainCheck and TCPT were cheaper (respective incremental costs -GBP148 [-EUR168.53] and -GBP474 [-EUR539.74]) and more effective (respective incremental QALYs of 0.010 and 0.013) than usual care. There was a 65 percent and 99.5 percent chance of cost-effectiveness for PainCheck and TCPT, respectively. Results were relatively robust to sensitivity analyses. The most important driver of cost-effectiveness was level of pain reduction (intervention effectiveness). Although cost savings were modest per patient, these were considerable when accounting for the number of potential intervention beneficiaries. Conclusions Educational and monitoring/feedback interventions have the potential to be cost-effective. Economic evaluations based on estimates of effectiveness from published meta-analyses and using a decision modeling approach can support commissioning decisions and implementation of pain management strategies

Détermination du débit de filtration glomérulaire (DFG) au cours du diabète : Cockroft et Gault, MDRD ou CKD-EPI ?

Plusieurs paramètres peuvent être étudiés pour évaluer le rein. Parmi ceux-ci, le débit de filtration glomérulaire (DFG) a été déterminé avec les formules de Cockroft et Gault (CG), du Modification of Diet in Renal Disease (MDRD) et du Chronic Kidney Disease EPIdemiology Collaboration (CKD-EPI) et la formule la mieux adaptée pour le diabétique a été recherchée. Chez 59 diabétiques de type 1 (DT1) et 70 diabétiques de type 2 (DT2), le DFG a été déterminé avec les formules de CG, du MDRD et du CKD-EPI. Avec l’analyse statistique, les seuils de significativité ont été fixés pour p<0,05 ; T0α>1,96 et Z0α>1,96. Le MDRD est superposable au CKD-EPI chez les DT1 et DT2. Chez les DT1, le DFG moyen et la corrélation entre 1/créatininémie et DFG ne varient pas si CG ou CKD-EPI ; cependant, les sujets à DFG réduit (< 90 ml/min/1,73 m²) sont plus nombreux avec CG plutôt qu’avec CKD-EPI (66,10% vs 47,46% ; T0α=2,05). Chez les DT2, le DFG moyen et la proportion de sujets à DFG réduit sont indépendants de la formule utilisée, mais la corrélation entre 1/créatininémie et DFG est plus forte si CKD-EPI que CG (0,961 vs 0,632 ; Z0α=7,02). Ainsi, la formule la mieux adaptée pour la détermination du DFG serait CG chez les DT1 et CKD-EPI chez les DT2, sachant que CKD-EPI est équivalent à MDRD quel que soit le type de diabète.Mots clés : Cockroft et Gault - MDRD - CKD-EPI – débit de filtration glomérulaire (DFG) – diabète