DNA vaccination of neonate piglets in the face of maternal immunity induces humoral memory and protection against a virulent pseudorabies virus challenge

DNA vaccination represents a unique opportunity to overcome the limitations of conventional vaccine strategy in early life in the face of maternal-derived immunity. We used the model of pseudorabies virus (PRV) infection in pigs to further explore the potential of DNA vaccination in piglets born to sows repeatedly vaccinated with a PRV inactivated vaccine. A single immunisation of 8-week-old piglets with a DNA vaccine expressing secreted forms of PRV gB, gC, and gD, triggered an active serological response, confirming that DNA vaccination can over-ride significant residual maternal-derived immunity. A clear anamnestic response was evidenced when a secondary DNA vaccination was performed at 11 weeks of age, suggesting that DNA vaccination, performed in the face of passive immunity, elicited a strong humoral memory. We subsequently explored the potential of DNA vaccination in neonate piglets (5-6 days of age) in the face of very high titres of maternal antibodies and demonstrated that very high titres of passive antibodies selectively inhibited serological responses but not the establishment of potent memory responses. Finally, we demonstrated that DNA vaccination provided protection against an infectious PRV challenge at the end of the fattening period (i.e. at approximately 5 months of age). Collectively, our results pave the way for a new flexible vaccination program, which could ensure uninterrupted protection of fattening pigs over their entire economical life under field conditions.     

Alcohol use and intoxication in sport university students

AIMS: To investigate patterns of alcohol consumption and intoxication in French sport science students. METHODS: Second- and third-year sport university students (n = 677) completed an anonymous self-report questionnaire. RESULTS AND CONCLUSIONS: 20.4% reported more than six episodes of intoxication during the previous year. Male students drank more frequently and were more frequently intoxicated than were female students. Compared to their peers in the general population, sport students drank less frequently, but reported more episodes of intoxication. There were no differences in frequency of intoxication according to competitive level.     

Comparative analysis of molecular alterations in fibroadenomas associated or not with breast cancer

HYPOTHESIS: The cause of breast cancer is linked to many macroscopic events, including benign breast disease. In this study we asked whether molecular changes could discriminate fibroadenoma, which is one of the most common benign breast disease lesions associated or not with breast cancer. DESIGN: Retrospective cohort study. SETTING: Anticancer medical center. SUBJECTS: Archival tissues in 32 cases of fibroadenoma, diagnosed in the same breast as a breast carcinoma, are compared with a control group of 26 cases of fibroadenomas unaffected by breast cancer. MAIN OUTCOME MEASURES: Histological features are characterized in all samples. The epithelial and stromal components are analyzed for a loss of heterozygosity and a microsatellite instability using a polymerase chain reaction-based method with 11 polymorphic microsatellite markers at 7 chromosomal regions frequently altered in breast cancer. The p53 gene mutations were also determined at exons 5 to 9. RESULTS: The frequency of complex fibroadenomas was similar in both groups (P =.42). Only in the case group did we observe proliferative lesions confined in fibroadenomas, including atypical ductal hyperplasia (2 cases), lobular neoplasia (3 cases), or low-grade ductal carcinoma in situ (2 cases). There is no significant morphological difference between the 2 groups. Neither microsatellite alterations nor p53 gene mutations are present in the fibroadenoma components. Loss of heterozygosity is found only in the epithelial component of the 2 ductal carcinomas in situ confined in fibroadenomas. CONCLUSIONS: Genetic alterations, which are most frequently involved in malignant breast carcinomas, are not present in fibroadenomas, regardless of their association with breast cancer or their histological complexity. These findings suggest that fibroadenomas are not associated with breast carcinogenesis.     

Improving the Glasgow Coma Scale score: motor score alone is a better predictor

BACKGROUND: The Glasgow Coma Scale (GCS) has served as an assessment tool in head trauma and as a measure of physiologic derangement in outcome models (e.g., TRISS and Acute Physiology and Chronic Health Evaluation), but it has not been rigorously examined as a predictor of outcome. METHODS: Using a large trauma data set (National Trauma Data Bank, N = 204,181), we compared the predictive power (pseudo R2, receiver operating characteristic [ROC]) and calibration of the GCS to its components. RESULTS: The GCS is actually a collection of 120 different combinations of its 3 predictors grouped into 12 different scores by simple addition (motor [m] + verbal [v] + eye [e] = GCS score). Problematically, different combinations summing to a single GCS score may actually have very different mortalities. For example, the GCS score of 4 can represent any of three mve combinations: 2/1/1 (survival = 0.52), 1/2/1 (survival = 0.73), or 1/1/2 (survival = 0.81). In addition, the relationship between GCS score and survival is not linear, and furthermore, a logistic model based on GCS score is poorly calibrated even after fractional polynomial transformation. The m component of the GCS, by contrast, is not only linearly related to survival, but preserves almost all the predictive power of the GCS (ROC(GCS) = 0.89, ROC(m) = 0.87; pseudo R2(GCS) = 0.42, pseudo R2(m) = 0.40) and has a better calibrated logistic model. CONCLUSION: Because the motor component of the GCS contains virtually all the information of the GCS itself, can be measured in intubated patients, and is much better behaved statistically than the GCS, we believe that the motor component of the GCS should replace the GCS in outcome prediction models. Because the m component is nonlinear in the log odds of survival, however, it should be mathematically transformed before its inclusion in broader outcome prediction models.     

Low-dose chest CT with millimetric thin slices: myth or reality?

PURPOSE: To evaluate the diagnostic accuracy of millimetric thin slices low dose chest CT. MATERIALS AND METHODS: Forty one patients underwent a chest CT thin slices (1 mm every 10 mm) exploration using both a 170 milliamperage and a low dose acquisition using 80 mA. The examination were read by 2 senior radiologists specialized in chest imaging without knowledge of acquisition parameters and in a random order. A statistical analysis of interobserver agreement was performed using Kappa analysis. Doses of both acquisition were estimated by compagning the dose length product calculated by the CT software and be using a simulation software. RESULTS: Excellent interobserver and intermodalities agreements were found. A 53% decrease in dose was estimated with the low dose modality compare to the normal dose. CONCLUSION: Low dose thin slice chest CT using 80 mA has a similar diagnosis accuracy as standard dose thin slice chest CT and delivers half dose of irradiation.     

A hand-held imaging probe for radio-guided surgery: physical performance and preliminary clinical experience

Improvements in the specificity of radiopharmaceutical compounds have been paralleled by an upsurge of interest in developing small detectors to assist surgeons in localizing tumour tissue during surgery. This study reports the main technical features and physical characteristics of a new hand-held gamma camera dedicated to accurate and real-time intra-operative imaging. First clinical experience is also reported. The POCI (Per-operative Compact Imager) camera consists of a head module composed of a high-resolution interchangeable lead collimator and a CsI(Na) crystal plate optically coupled to an intensified position-sensitive diode. The current prototype has a 40-mm diameter field of view, an outer diameter of 9.5 cm, a length of 9 cm and a weight of 1.2 kg. Overall detector imaging characteristics were evaluated by technetium-99m phantom measurements. Three patients with breast cancer previously scheduled to undergo sentinel lymph node detection were selected for the preliminary clinical experience. Preoperative images of the lymphatic basin obtained using the POCI camera were compared with conventional transcutaneous explorations using a non-imaging gamma probe. The full-width at half-maximum (FWHM) spatial resolution was investigated in both air and scattering medium; when the phantom was placed in contact with the collimator, the POCI camera exhibited a 3.2 mm FWHM. The corresponding sensitivity was 290 cps/MBq. The preliminary clinical results showed that POCI was able to predict the number and location of all SLNs. In one case, two deep radioactive nodes missed by the gamma probe were detected on the intra-operative images. This very initial experience demonstrates that the physical performance of the POCI camera is adequate for radio-guided surgery. These results are sufficiently encouraging to prompt further evaluation studies designed to determine the specific and optimal clinical role of intra-operative imaging devices.     

Short course dexamethasone treatment following injury inhibits bleomycin induced fibrosis in rats

BACKGROUND: Corticosteroids are routinely used in patients with pulmonary fibrosis. The timing for initiation of treatment is likely to be crucial for corticosteroids to exert an antifibrotic effect. Experimental studies in animals have examined the effect of corticosteroid treatment starting before or at the time of lung injury. However, this is not representative of the human condition as treatment only begins after disease has been established. We examined the effect of a short course corticosteroid treatment starting 3 days after bleomycin induced lung injury on the development of pulmonary fibrosis. METHODS: Bleomycin (1.5 mg/kg) was instilled intratracheally into rats to induce pulmonary fibrosis. The effect of a 3-day course of dexamethasone (0.5 mg/kg) initiated 3 days after bleomycin induced lung injury on cell proliferation and collagen deposition was examined by analysing bronchoalveolar lavage (BAL) fluid and lung tissue. RESULTS: Treating bleomycin exposed animals after injury with dexamethasone for 3 days inhibited lung collagen deposition compared with animals exposed to bleomycin without dexamethasone treatment (15.2 (2.2) mg collagen/lung v 22.5 (2.1) mg/lung; p<0.05). Dexamethasone treatment reduced pulmonary parenchymal cell proliferation in bleomycin exposed rats but did not influence BAL fluid mitogenic activity for lung fibroblasts or alter the BAL fluid levels of the fibrogenic mediators transforming growth factor-beta(1), platelet derived growth factor-AB, and thrombin. CONCLUSIONS: A 3 day course of dexamethasone treatment initiated 3 days after bleomycin induced lung injury reduces lung cell proliferation and collagen deposition by mechanisms other than through reduction of transforming growth factor-beta(1), platelet derived growth factor-AB, and thrombin levels in BAL fluid. We propose that an early short course treatment with dexamethasone may be useful in inhibiting pulmonary fibrosis.