Survivin in Brain Tumors: An Attractive Target for Immunotherapy

Survivin, a member of the inhibitor of apoptosis proteins gene family, was recently shown to be expressed by tumors originating from different cell lineages. There are also cumulative evidences that spontaneous immune response against survivin derived epitopes may occur. Here, using RT-PCR, Western-blot analysis and immunohistochemistry, we show that survivin is widely expressed by gliomas, meningiomas and schwannomas, both in vitro and in vivo. These data indicate that survivin may serve as an attractive target for immunotherapies designed for brain tumors.     

Prevention of acquired infections in intubated patients with the combination of two decontamination regimens

OBJECTIVE: The use of topical polymyxin and tobramycin to prevent intensive care infections is controversial. Moreover, these antibiotics are ineffective against methicillin-resistant Staphylococcus aureus. A decontamination regimen using mupirocin and chlorhexidine could prevent acquired infections, including those involving S. aureus. Because these two regimens could have a complementary role, we evaluated their effects when given both alone and combined. DESIGN: The authors conducted a multiple-center, placebo-controlled, randomized, double-blind study performed according to a 2 x 2 factorial design. SETTING: The study was conducted at three polyvalent medical intensive care units at university-affiliated hospitals in France. PATIENTS: Adult patients (age, > or =18 yrs) intubated for <48 hrs who were likely to be ventilated for >48 hrs. INTERVENTION: Two regimens were used: topical administration of polymyxin/tobramycin (or placebo) and nasal mupirocin with chlorhexidine body washing (or nasal placebo with liquid soap). The patients (n = 515) received polymyxin/tobramycin alone (n = 130), mupirocin/chlorhexidine alone (n = 130), both regimens (n = 129), or all placebos (n = 126) for the period of mechanical ventilation plus 24 hrs. MEASUREMENTS AND MAIN RESULTS: The incidence of total infections acquired from the date of randomization until the termination date of study treatments plus 48 hrs was assessed. There were fewer acquired infections with both regimens than with polymyxin/tobramycin alone (odds ratio, 0.44; 95% confidence interval, 0.26-0.75; p = .003), mupirocin/chlorhexidine alone (0.43; 0.25-0.73; p = .002), or all placebos (0.42; 0.25-0.72; p = .001). There were no differences between polymyxin/tobramycin alone (0.95; 0.59-1.54; p = .84) and mupirocin/chlorhexidine alone (0.98; 0.60-1.58; p = .92) vs. all placebos. The probability of freedom from infection was higher with both regimens than with polymyxin/tobramycin alone (p = .002), mupirocin/chlorhexidine alone (p < .001), or all placebos (p < .001). Infection rates were also significantly lower with both regimens than with polymyxin/tobramycin alone (p = .017), mupirocin/chlorhexidine alone (p < .001), or all placebos (p < .001). CONCLUSION: Acquired infections were substantially reduced by mupirocin/chlorhexidine plus polymyxin/tobramycin, whereas each regimen given alone was ineffective. Whether both regimens could increase Candida infections deserves further investigation.     

Changes in staphylococcal cassette chromosome type and antibiotic resistance profile in methicillin-resistant Staphylococcus aureus isolates from a French hospital over an 11 year period

BACKGROUND: In this study, we investigated the relationship between changes in antibiotic resistance and distribution of staphylococcal cassette chromosome (SCC) types amongst methicillin-resistant Staphylococcus aureus (MRSA) isolates expressing the most frequently encountered profiles of antibiotic resistance over an 11 year period in the University Hospital of Rennes, France. METHODS: Antibiotic susceptibilities were determined by agar diffusion. SCC typing was performed using PCR. PFGE demonstrated that isolates were phylogenetically related. RESULTS: Fourteen profiles of antibiotic resistance were defined among MRSA isolates. For each resistance profile, only one SCC type was associated: four patterns corresponded to SCC type I or IA, nine to SCC type IV or IVA, and none to types II and III. One was not typed. PFGE indicated that isolates with SCC type I or IA belong to a single genetic lineage, which also includes most of the epidemic isolates, which carry SCC type IVA. In contrast to type I or IA, isolates with SCC type IV or IVA were found to be associated with several different PFGE clusters, although not all of these represent epidemic isolates. CONCLUSIONS: During the course of the study, the spectrum of antibiotic resistance in MRSA isolates decreased. This occurred due to the emergence of strains with SCC type IV or IVA, which are susceptible to more antibiotics than type I or IA strains. The greater prevalence of such isolates could not be linked conclusively to the presence of SCC type IV or IVA, or to one particular PFGE cluster.     

Intensity dependence of auditory evoked potentials during light interference in migraine

Abnormal decision-making (DM) performance has been reported in several neurobehavioral disorders such as schizophrenia, addiction, and obsessive compulsive disorders. The exploration of DM correlates in terms of symptom formation may add more knowledge about the meanings of DM performance in schizophrenia. We examined the Iowa Gambling Task (IGT) and its relationship with clinical symptoms, evaluated by Positive and Negative Symptom Scale (PANSS), in 40 schizophrenic patients and 20 controls. Schizophrenic patients did worse on IGT performance with a significant difference between the two groups in Net Score. PANSS positive symptoms were negatively correlated with Net Score and advantageous choices and directly with disadvantageous choices. Results suggest that persons with schizophrenia display a pattern of compromised DM related to positive symptoms.     

The circumventricular organs: an atlas of comparative anatomy and vascularization

The circumventricular organs are small sized structures lining the cavity of the third ventricle (neurohypophysis, vascular organ of the lamina terminalis, subfornical organ, pineal gland and subcommissural organ) and of the fourth ventricle (area postrema). Their particular location in relation to the ventricular cavities is to be noted: the subfornical organ, the subcommissural organ and the area postrema are situated at the confluence between ventricles while the neurohypophysis, the vascular organ of the lamina terminalis and the pineal gland line ventricular recesses. The main object of this work is to study the specific characteristics of the vascular architecture of these organs: their capillaries have a wall devoid of blood-brain barrier, as opposed to central capillaries. This particular arrangement allows direct exchange between the blood and the nervous tissue of these organs. This work is based on a unique set of histological preparations from 12 species of mammals and 5 species of birds, and is taking the form of an atlas.     

Duration-dependent cytoprotective versus inflammatory effects of lung epithelial fibroblast growth factor-7 expression

Fibroblast growth factor-7 (FGF7) is a lung epithelial cell mitogen that is cytoprotective during injury. Transgenic mice that conditionally expressed FGF7 were used to dissect the mechanisms of FGF7 protection during lung injury. FGF7 improved survival when induced 3 days prior to acute lung injury. In contrast, FGF7 caused pulmonary inflammation and lung injury after 7 days or longer. Gene expression analysis of mouse lung mRNA identified mRNAs that contribute to the protective effects of FGF7. FGF7 improved survival during acute lung injury in adult mouse lung after short-term expression, but paradoxically induced inflammation and injury after persistent expression.