Cowpox Virus Transmission from Pet Rats to Humans, France

In early 2009, four human cases of cowpox virus cutaneous infection in northern France, resulting from direct contact with infected pet rats (Rattus norvegicus), were studied. Pet rats, originating from the same pet store, were shown to be infected by a unique virus strain. Infection was then transmitted to humans who purchased or had contact with pet rats.     

Slow disease progression and robust therapy-mediated CD4+ T-cell recovery are associated with efficient thymopoiesis during HIV-1 infection

In chronic HIV infection, most untreated patients lose naive CD4+ and CD8+ T cells, whereas a minority preserve them despite persistent high viremia. Although antiretroviral therapy (ART)-mediated viral suppression generally results in a rise of naive and total CD4+ T cells, certain patients experience very little or no T-cell reconstitution. High peripheral T-cell activation has been linked to poor clinical outcomes, interfering with previous evaluations of thymic function in disease progression and therapy-mediated T-cell recovery. To circumvent this, we used the sj/betaTREC ratio, a robust index of thymopoiesis that is independent of peripheral T-cell proliferation, to evaluate the thymic contribution to the preservation and restoration of naive CD4+ T cells. We show that the loss of naive and total CD4+ T cells is the result of or is exacerbated by a sustained thymic defect, whereas efficient thymopoiesis supports naive and total CD4+ T-cell maintenance in slow progressor patients. In ART-treated patients, CD4+ T-cell recovery was associated with the normalization of thymopoiesis, whereas the thymic defect persisted in aviremic patients who failed to recover CD4+ T-cell counts. Overall, we demonstrate that efficient thymopoiesis is key in the natural maintenance and in therapy-mediated recovery of naive and total CD4+ T cells.     

Co-morbid health conditions at mid-life in the Iowa adoptees

Adverse health effects due to alcohol and illicit drug abuse and dependence have been well documented. This study examines the effect of substance misuse on five major groups of health conditions using a sample of well characterized adoptees. The sample consisted of 742 adoptees interviewed in the last wave of the Iowa Adoption Studies. Death rate analyses included an additional 34 participants who had died prior to the last follow-up. Substance use patterns and medical history were assessed using the SSAGA-II (Bucholz, K. K., Cadoret, R. J., Cloninger, C. R., Dinwiddie, S. H., Hesselbrock, V. M., Nurnberger, J. L., Jr., et al. (1994). A new, semi-structured psychiatric interview for use in genetic linkage studies: a report on the reliability of the SSAGA. Journal of Studies on Alcohol, 55 (2), 149-158). Subjects were divided into three groups according to DSM-IV diagnostic criteria, controls, alcohol abuse or dependence only (alcohol only), and the Alcohol-Drug group (abuse or dependence diagnosis on at least one illicit substance with or without alcohol diagnosis). Incidence rates of various diseases were measured using logistic regression. Survival analyses were used to examine whether substance abusers developed cardiovascular or metabolic disease at an earlier age than control subjects. Diagnostic grouping made no difference in the incidence rates or age of onset of health conditions. The amount of alcohol consumed by males significantly predicted higher number of overall health complaints as well as higher incidence rates of cardiovascular disease. The amount of illicit drug exposure did not predict an earlier age of diagnosis for cardiovascular or metabolic disease. Individuals in the Alcohol-Drug group had an increased incidence of deaths than either the alconly or the control groups.     

Prospective study comparing hepatic steatosis assessment by magnetic resonance imaging and four ultrasound methods in 105 successive patients

BACKGROUND Non-alcoholic fatty liver disease(NAFLD) is becoming a major health problem, resulting in hepatic, metabolic and cardio-vascular morbidity.AIM To evaluate new ultrasonographic tools to detect and measure hepatic steatosis.METHODS We prospectively included 105 patients referred to our liver unit for NAFLD suspicion or follow-up. They underwent ultrasonographic measurement of liver sound speed estimation(SSE) and attenuation coefficient(AC) using Aixplorer MACH 30(Supersonic Imagine, Fr...     

The synthetic pentasaccharide fondaparinux prevents coronary microvascular injury and myocardial dysfunction in the ischemic heart

Fondaparinux is a synthetic pentasaccharide with powerful anticoagulant properties, which may also reduce ischemia-reperfusion (I/R) injury in vivo. However, the relative contributions of the anticoagulant and anti-inflammatory activities of fondaparinux to the observed protection are unknown. To address this issue, a crystalloid-perfused heart model was used to assess potential effects of fondaparinux on IR-induced heart injury in the absence of blood. Fondaparinux protects the ischemic myocardium independently of its haemostasis effects. Fondaparinux improved post ischemic myocardial contractile performance and tissue damage. These beneficial effects of fondaparinux may be related to the observed reduction in IR-induced oxidative stress and endothelial activation. In addition, fondaparinux altered NADPH oxidase activity and phosphorylated extracellular signal-regulated kinase (ERK) 1/2, suggesting activation of survival signaling pathways. The present study provides novel information by demonstrating that fondaparinux can attenuate inflammatory responses and oxidative stress in connection with IR heart injury. These findings could represent a potential therapeutic strategy for the prevention of myocardial dysfunction.     

A mean three-dimensional atlas of the human thalamus: Generation from multiple histological data

Functional neurosurgery relies on robust localization of the subcortical target structures, which cannot be visualized directly with current clinically available in-vivo imaging techniques. Therefore, one has still to rely on an indirect approach, by transferring detailed histological maps onto the patient's individual brain images. In contrast to macroscopic MRI atlases, which often represent the average of a population, each stack of sections, which a stereotactic atlas provides, is based on a single specimen. In addition to this bias, the anatomy is displayed with a highly anisotropic resolution, leading to topological ambiguities and limiting the accuracy of geometric reconstruction. In this work we construct an unbiased, high-resolution three-dimensional atlas of the thalamic structures, representing the average of several stereotactically oriented histological maps. We resolve the topological ambiguity by combining the information provided by histological data from different stereotactic directions. Since the stacks differ not only in geometrical detail provided, but also due to inter-individual variability, we adopt an iterative approach for reconstructing the mean model. Starting with a reconstruction from a single stack of sections, we iteratively register the current reference model onto the available data and reconstruct a refined mean three-dimensional model. The results show that integration of multiple stereotactic anatomical data to produce an unbiased, mean model of the thalamic nuclei and their subdivisions is feasible and that the integration reduces problems of atlas reconstruction inherent to histological stacks to a large extent.     

Surgical treatment strategies and outcome in patients with breast cancer metastatic to the spine: a review of 87 patients

Aggressive surgical management of spinal metastatic disease can provide improvement of neurological function and significant pain relief. However, there is limited literature analyzing such management as is pertains to individual histopathology of the primary tumor, which may be linked to overall prognosis for the patient. In this study, clinical outcomes were reviewed for patients undergoing spinal surgery for metastatic breast cancer. Respective review was done to identify all patients with breast cancer over an eight-year period at a major cancer center and then to select those with symptomatic spinal metastatic disease who underwent spinal surgery. Pre- and postoperative pain levels (visual analog scale [VAS]), analgesic medication usage, and modifed Frankel grade scores were compared on all patients who underwent surgery. Univariate and multivariate analyses were used to assess risks for complications. A total of 16,977 patients were diagnosed with breast cancer, and 479 patients (2.8%) were diagnosed with spinal metastases from breast cancer. Of these patients, 87 patients (18%) underwent 125 spinal surgeries. Of the 76 patients (87%) who were ambulatory preoperatively, the majority (98%) were still ambulatory. Of the 11 patients (13%) who were nonambulatory preoperatively, four patients were alive at 3 months postoperatively, three of which (75%) regained ambulation. The preoperative median VAS of six was significantly reduced to a median score of two at the time of discharge and at 3, 6, and 12 months postoperatively (P < 0.001 for all time points). A total of 39% of patients experienced complications; 87% were early (within 30 days of surgery), and 13% were late. Early major surgical complications were significantly greater when five or more levels were instrumented. In patients with spinal metastases specifically from breast cancer, aggressive surgical management provides significant pain relief and preservation or improvement of neurological function with an acceptably low rate of complications.     

d-Amphetamine-induced hepatotoxicity: possible contribution of catecholamines and hyperthermia to the effect studied in isolated rat hepatocytes

Amphetamines are indirect-acting sympathomimetic drugs widely abused due to their physical and psychostimulating effects. However, the use of these drugs has been associated with numerous reports of hepatotoxicity. While glutathione depletion induced by amphetamines contributes to the exposure of hepatocytes to oxidative damage, other indirect effects attributed to amphetamines may have a role in cell injury. To examine this possibility, Wistar rats were used for plasma measurements of d-amphetamine and catecholamines (noradrenaline, adrenaline and dopamine) (15 min) after i.p. injection of d-amphetamine (5, 20 and 80 mg/kg). Freshly isolated rat hepatocytes were put into contact for 2 h with concentrations of d-amphetamine and catecholamines similar to those found in vivo. Since hyperthermia is a common consequence of acute amphetamine intake, the study using isolated hepatocytes was conducted at 37 °C and also at 41 °C in order to simulate high temperature levels. We found that hyperthermia was an important cause of cell toxicity: in vitro, a rise in incubation temperature from 37 to 41 °C causes oxidative stress in freshly isolated rat hepatocytes, as shown by a depletion of reduced glutathione (GSH; 23%), an increase of oxidized glutathione (GSSG; 157%), the induction of lipid peroxidation with 77% increase of thiobarbituric acid substances TBARS) and the consequent loss of cell viability (≤ 44%). Single treatment of isolated hepatocytes with catecholamines at 37 °C induced lipid peroxidation (29% increase of TBARS) but had no effect on glutathione or cell viability. Conversely, a single treatment with d-amphetamine induced glutathione depletion (≤ 24% depletion of GSH) with no effect on lipid peroxidation or cell viability. Also, d-amphetamine potentiated the induction by catecholamines of lipid peroxidation at 37 °C (≤ 48% increase of TBARS), while concomitant treatment of d-amphetamine and catecholamines potentiated cell death at 41 °C (≤ 56% of cell death) although no effect on viability was seen at 37 °C. It is concluded that the aforementioned modifications induced by d-amphetamine in vivo are cytotoxic to freshly isolated rat hepatocytes. Received: 30 October 1996 / Accepted: 13 January 1997