Health-related quality of life and cognitive failures in patients with lower-grade gliomas treated with radiotherapy.

PURPOSE: Patients with lower grade (grade 2 and 3) glioma (LGG) frequently experience prolonged clinical course after multimodal therapy (including surgery, radiotherapy (RT), and chemotherapy). There is therefore significant concern about the potential long-term impact of the disease and treatments on quality of life (QOL) and cognitive functioning. In this context, we evaluated health related QOL and cognitive failures in LGG patients previously treated in our RT department. PATIENTS AND METHODS: Adult LGG patients previously treated with RT were prospectively included. Patients were evaluated based on standardized questionnaires [i.e., EORTC QLQ-C30, EORTC QLQ-BN20, and cognitive failures questionnaire (CFQ)]. RESULTS: Forty-eight patients were included. Median time elapsed since the end of RT was 59.5 months (range: 4-297). Based on EORTC QLQ-C30 and QLQ-BN20, the most prevalent HRQOL issues were impaired cognitive functioning (50% of the patients), impaired emotional functioning (47.9%), financial difficulties (43.7%), fatigue (43.7%), future uncertainty (39.6%), and impaired physical functioning (35.4%). Based on the CFQ, 35.4% of the patients showed increased tendency to cognitive failures. CONCLUSION: Patients with LGG frequently experience impairments in HRQOL and cognitive failures after treatment (including RT). Further efforts are therefore warranted to improve the QOL and cognitive outcome of these patients.

Vestibular evoked myogenic potentials.

Vestibular Evoked Myogenic Potentials (VEMP) are commonly recorded in patients experiencing vertigo or chronic instability. This test evaluates the patient's otolith function and is often combined with both Videonystagmography and Video Head Impulse Test. VEMP is a simple, reproducible test, in the absence of any pre-existing conductive hearing loss. Cervical VEMP explore both saccular function and the inferior vestibular nerve, whereas ocular VEMP assess utricular function and the superior vestibular nerve. In combination with previously described tests, VEMP allows characterization of vertigo and provides support for the diagnosis of superior semicircular canal dehiscence syndrome, Menière's disease, vestibular neuritis, vestibular schwannoma or idiopathic bilateral vestibulopathy. A good knowledge of these electrophysiological tests is essential in order to precisely assess the presence or absence of vestibular function impairment. We describe the test recording technique and the most common pitfalls in interpretation of the results. We then outline the results observed in various diseases impacting vestibular function.

Substitution of 11C-methionine PET by perfusion MRI during the follow-up of treated high-grade gliomas: preliminary results in clinical practice.

PURPOSE: Our aim was to compare perfusion magnetic resonance imaging (MRI) and positron emission tomography (PET) using carbon-11 labelled methionine (MET) in gliomas and their value in differentiating tumour recurrence from necrosis. MATERIALS AND METHODS: We retrospectively reviewed 28 patients with a high-grade glioma. A total of 33MR perfusions and MET-PET were ultimately analysable for comparison between the relative cerebral blood volume (rCBV) and MET-PET examinations. Intra- and interobserver reproducibility was assessed and diagnostic value of rCBV compared to MET-PET and histology was assessed by the area under the receiver operating characteristic (ROC) curve. RESULTS: ROC curve analysis showed that rCBV had at least equal performances in differentiating tumour recurrence and necrosis than MET-PET. Cut-off value of rCBV for differentiating tumour from necrosis was 182% with a sensitivity of 81.5% and a specificity of 100%. CONCLUSION: In clinical practice, perfusion MRI could replace MET-PET for differentiating necrosis from tumour recurrence.

[Fever with skin rash and polyarthralgia in a genetically black-skinned woman]. / Eruption cutanée et polyarthralgie fébrile chez une femme génétiquement pigmentée.

Adult onset Still's disease (AOSD) is a systemic disorder characterized by intermittent fever, evanescent rash, polyarthralgia or arthritis, and neutrophilic leucocytoclasis. Appearance of skin rash during fever episodes is the characteristic feature. An atypical form of AOSD with a fixed pigmented skin rash was described in 1994. Prognosis of the atypical form is thought to be more severe than that of the classic form. The purpose of this report is to describe the first case of atypical AOSD in a genetically black-skinned woman. Treatment required administration of high-dose systemic corticosteroids.

Proteomic analysis of mouse hypothalamus under simulated microgravity.

Exposure to altered microgravity during space travel induces changes in the brain and these are reflected in many of the physical behavior seen in the astronauts. The vulnerability of the brain to microgravity stress has been reviewed and reported. Identifying microgravity-induced changes in the brain proteome may aid in understanding the impact of the microgravity environment on brain function. In our previous study we have reported changes in specific proteins under simulated microgravity in the hippocampus using proteomics approach. In the present study the profiling of the hypothalamus region in the brain was studied as a step towards exploring the effect of microgravity in this region of the brain. Hypothalamus is the critical region in the brain that strictly controls the pituitary gland that in turn is responsible for the secretion of important hormones. Here we report a 2-dimensional gel electrophoretic analysis of the mouse hypothalamus in response to simulated microgravity. Lowered glutathione and differences in abundance expression of seven proteins were detected in the hypothalamus of mice exposed to microgravity. These changes included decreased superoxide dismutase-2 (SOD-2) and increased malate dehydrogenase and peroxiredoxin-6, reflecting reduction of the antioxidant system in the hypothalamus. Taken together the results reported here indicate that oxidative imbalance occurred in the hypothalamus in response to simulated microgravity.

Activation of activator protein-1 in mouse brain regions exposed to simulated microgravity.

Microgravity induces stress, and the brain is one of the targets that is more influenced in this environment. Alteration in transcription factors can have enormous effect because of discrepancy in the signaling process of the cells. Activator protein-1 (AP-1) is a stress-regulated transcription factor and is involved in the regulation of physiological and pathological stimuli that include cytokines, growth factors, and stress signals. In the present study, an attempt has been made to observe the effect of a microgravity environment on the activation of AP-1 in the mouse brain. Our results show that AP-1 transcription factor is activated in simulated microgravity conditions in different regions of the brain. The activation of the AP-1 is dependent upon the increased kinase activity of c-Jun NH-terminal2 kinase-1. These results suggest that microgravity stress in the brain can elicit AP-1 activity.

Proteomic analysis of mice hippocampus in simulated microgravity environment.

Space travel induces many deleterious effects on the flight crew due to the '0' g environment. The brain experiences a tremendous fluid shift, which is responsible for many of the detrimental changes in physical behavior seen in astronauts. It therefore indicates that the brain may undergo major changes in its protein levels in a '0' g environment to counteract the stress. Analysis of these global changes in proteins may explain to better understand the functioning of brain in a '0' g condition. Toward such an effort, we have screened proteins in the hippocampus of mice kept in simulated microgravity environment for 7 days and have observed a few changes in major proteins as compared to control mice. Essentially, the results show a major loss of proteins in the hippocampus of mice subjected to simulated microgravity. These changes occur in structural proteins such as tubulin, coupled with the loss of proteins involved in metabolism. This preliminary investigation leads to an understanding of the alteration of proteins in the hippocampus in response to the microgravity environment.

Implementation of isolation precautions: role of a targeted information flyer.

Isolation precautions are advocated in most countries for patients harbouring multi-drug-resistant organisms. We evaluated the impact of a targeted information flyer on the implementation of isolation precautions for patients with methicillin-resistant Staphylococcus aureus (MRSA). A flyer providing a quick reference to the steps to be implemented following detection of MRSA was sent systematically by the microbiologists with all results displaying MRSA. Infection control staff compared isolation precautions in two three-month periods: the first (control) period before implementation of the flyer and the second (intervention) period after implementation of the flyer. Compared with the control period, compliance with isolation precautions increased significantly in the intervention period. In intensive care units, there was a sign posted on the door for 31 of 38 (82%) patients in the control period, and 33 out of 34 (97%) in the intervention period (P=0.06). Use of gowns increased from 82% to 100% (P=0.01), use of dedicated materials increased from 84% to 100% (P=0.03), availability of alcohol hand rub increased from 82% to 94% (P=0.10), and the proportion of MRSA patients in private rooms increased from 71% to 91% of the cases (P=0.07). In conclusion, compliance with isolation precautions increased after attaching a flyer to all MRSA-positive bacteriological results.

Measurement of volatile organic compounds in the urban atmosphere of Harris County, Texas, USA.

Volatile organic compounds (VOCs) are a major component of urban air pollution. It is well documented that exposure to certain types of VOCs can cause adverse health effects such as cancer, immune and neurological damage, and reproductive and endocrine disorders. Urban air samples were collected at five locations in Harris County, Texas to determine the measurement of VOCs in the ambient air of residential areas in close proximity to industrial facilities that emit toxic air pollutants into the air. Three locations used in this study were located along the Houston Ship Channel (HSC), in the heart of one of the largest petrochemical complexes in the nation. Two other sampling locations were located many miles away from the ship channel and any industrial facilities that are required to report toxic air emissions. Air samples were collected daily over an 8-h period from December 2002 to March 2003. The samples were collected in 6-L stainless steel Silonite-coated canisters and analyzed using a modified version of EPA Method TO-15. A total of 53 compounds was quantitated using a gas chromatograph mass spectrometer system coupled to a cryogenic preconcentrator. Eighteen alkanes and oxygenated compounds were identified, along with 7 alkenes and 5 aromatic compounds. Several alkanes such as butane, isobutane, 2-methyl butane, and pentane were detected at all five sites. The total VOC concentrations determined were highest at two of the industrial sites and lowest at the site farthest away from the ship channel and any industrial facilities. This study concluded that the atmosphere near Harris County's industrial complex had higher concentrations of VOCs than the atmosphere in areas farther away from the HSC. The atmosphere of areas downwind from emission sources were found to be directly affected by toxic air emissions from industrial process but not at the levels seen in areas closer to the HSC.

Activation of nuclear transcription factor-kappaB in mouse brain induced by a simulated microgravity environment.

Microgravity induces inflammatory responses and modulates immune functions that may increase oxidative stress. Exposure to a microgravity environment induces adverse neurological effects; however, there is little research exploring the etiology of these effects resulting from exposure to such an environment. It is also known that spaceflight is associated with increase in oxidative stress; however, this phenomenon has not been reproduced in land-based simulated microgravity models. In this study, an attempt has been made to show the induction of reactive oxygen species (ROS) in mice brain, using ground-based microgravity simulator. Increased ROS was observed in brain stem and frontal cortex with concomitant decrease in glutathione, on exposing mice to simulated microgravity for 7 d. Oxidative stress-induced activation of nuclear factor-kappaB was observed in all the regions of the brain. Moreover, mitogen-activated protein kinase kinase was phosphorylated equally in all regions of the brain exposed to simulated microgravity. These results suggest that exposure of brain to simulated microgravity can induce expression of certain transcription factors, and these have been earlier argued to be oxidative stress dependent.

[Treatment of cutaneous metastases of a squamous cell carcinoma of the leg with topical miltefosine]. / Traitement de métastases cutanées d'un carcinome épidermoïde de la jambe par applications de miltéfosine.

INTRODUCTION: Miltefosine (Hexadecylphosphocholine) is a chemotherapy, which when applied locally, has demonstrated efficacy in the treatment of cutaneous metastases of breast cancer. CASE REPORT: A 79 year-old woman developed recurrent in transit cutaneous metastases of a squamous cell carcinoma on her left leg. All lesions completely resolved after topical applications of miltefosine. Tolerance was excellent and the patient remained disease-free 24 months after the end of the treatment. DISCUSSION: Miltefosine, which might prove to be a simple and effective alternative for the usually heavy treatments proposed, warrants further assessment in this context.

Concurrent spinal cord and vertebral bone marrow radionecrosis 8 years after therapeutic irradiation.

Concurrent radionecrosis within the spinal cord and the bone marrow at the same thoracic level was observed 8 years after localized therapeutic irradiation in a patient who had undergone repeated cycles of radiotherapy, glucocorticoid treatment, and chemotherapy for a non-Hodgkin's lymphoma. Mechanisms combining radiotoxic potentialization by glucocorticoids/alkylating agents and delayed radiation-induced vasculitis involving the common arterial pathways to the spinal cord and to the vertebrae were speculated to have acted in a synergistic way.

Comparison of setup accuracy of three different thermoplastic masks for the treatment of brain and head and neck tumors.

PURPOSE: Setup accuracy is an important factor influencing the definition of the planning target volume (PTV). The purpose of this study was to compare the setup accuracy of three different thermoplastic masks used for immobilization of patients with brain or head and neck tumors. MATERIALS AND METHODS: Thirty patients with brain or head and neck tumors were consecutively assigned to one of three different thermoplastic masks (Posifix): head mask with three fixation points (3 FP, ten patients), head and shoulder mask with four fixation points (4 FP, ten patients), head and shoulder mask with five fixation points (5 FP, four fixations plus an additional one on the top of head, ten patients). Once a week, during the session with a 6 MV linac (Elekta), orthogonal (antero-posterior and lateral) portal images were acquired for three fictitious isocenters placed during the simulation at the level of the head, the neck and the shoulders. Portal images and digitized simulator films were compared using the PIPS pro software, and displacements in antero-posterior (A-P), cranio-caudal (C-C) and medio-lateral (M-L) directions were calculated. From these displacements, 2D or 3D errors were also calculated. RESULTS: A total of 915 portal images were obtained, of which 98% could be analyzed. For the whole population, total displacements reached a standard deviation (SD) of 2.2 mm at the level of the head and the neck. Systematic and random displacements were in the same order of magnitude and reached a SD of 1.8 mm. Patient setup was slightly worse at the shoulder level with a total displacement of 2.8 mm (1 SD) for both the C-C and the M-L directions. There again, the systematic and the random components were in the same order of magnitude below 2.4 mm (+/-SD). For isocenters in the head and in the neck, there was no substantial difference in the setup deviation between the three masks. The setup reproducibility was found to be significantly worse (P=0.01) at the level of the shoulders with the 3 FP mask. For the 2D random error, 1 SD of 2.3 mm was observed compared to 0.8 and 1.2 mm for the 4 and 5 FP masks, respectively. Lastly, 90% of the 3D total deviations were below 4.5 mm for the head and the neck. In the shoulder region, 90% of the 2D total deviations were below 5.5 mm. CONCLUSION: Thermoplastic masks provide an accurate patient immobilization. At the shoulder level, setup variations are reduced when 4 or 5 FP masks are used. These data could be used for the assessment of margins for the PTV.

Optic nerve sheath meningiomas: clinical features, functional prognosis and controversial treatment.

Optic nerve sheath meningiomas (ONSM) are rare benign neoplastic lesions arising from meningothelial cells of the meninges. As clinical features are highly variable, the diagnosis is often delayed. From 1995 to 1999, 6 patients were diagnosed with ONSM in our department. We compared our series with the literature data. Visual prognosis is usually poor. Despite a large literature, the treatment guidelines are still highly controversial.

Chondrosarcoma of the base of the skull: a clinicopathologic study of 200 cases with emphasis on its distinction from chordoma.

Conventional chondrosarcoma (CSA) of the skull base is an uncommon neoplasm that can resemble chordoma, and indeed it is misdiagnosed frequently as such. This has important clinical implications, because when treated with similar aggressive treatment strategies, CSA has a much better prognosis than chordoma. In an effort to identify those morphologic and immunohistochemical features that help to identify conventional skull base CSA correctly and to understand its prognosis better, particularly compared with chordoma, when treated with surgery and proton beam irradiation, the authors performed a clinicopathologic analysis of 200 CSAs. The patients ranged in age from 10 to 79 years (mean, 39 years), 87 patients were male and 113 patients were female, and most presented with symptoms related to the central nervous system. Approximately 6% of the tumors arose in the sphenoethmoid complex, 28% originated in the clivus, and 66% developed in the temperooccipital junction. Histologically, 15 tumors (7.5%) were classified as hyaline CSA, 59 (29.5%) as myxoid CSA, and 126 (63%) as mixed hyaline and myxoid CSA. A total of 101 (50.5%) tumors were grade 1, 57 (28.5%) had areas of grades 1 and 2, and 42 (21%) were pure grade 2 neoplasms. The vast majority of patients originated from referring hospitals, and the diagnosis was changed prospectively at our institution to CSA from chordoma in 74 patients (37%). Of the tumors studied immunohistochemically, 96 of 97 (98.9%) stained for S-100 protein, 0 of 97 (0%) stained for keratin, and faint staining for epithelial membrane antigen was seen in 7 of 88 tumors (7.95%). All patients underwent high-dose postoperative fractionated precision conformal radiation therapy with a dose that ranged from 64.2 to 79.6 Cobalt-Gray-equivalents (median, 72.1 Cobalt-Gray-equivalents, given in 38 fractions. The 200 patients had a median follow-up of 63 months (range, 2.1 mos - 18.5 yrs). Tumor control was defined as lack of progression by clinical and radiographic assessment. Based on this definition, there were three local recurrences, and two of these patients died of tumor-related complications. The 5- and 10-year local control rates were 99% and 98% respectively, and the 5- and 10-year disease-specific survival rates were both 99%. In contrast to CSA, the 5- and 10-year survival rates of chordoma have been reported to be approximately 51 % and 35% respectively, and in our institution intensive treatment has resulted in 5- and 10-year progression-free survival rates of 70% and 45% respectively. CSA of the skull base can be distinguished reliably from chordoma, and this distinction is important because skull base CSA has an excellent prognosis when treated with surgery and proton beam irradiation, whereas chordomas have a substantially poorer clinical course despite similar aggressive management.

[Possibilities of psychoanalytic treatment in child and adolescent psychiatry in France]. / Psychoanalytische Behandlungsmöglichkeiten in der Kinder- und Jugendpsychiatrie in Frankreich.

This article describes the context of psychoanalytical approaches and their influence upon child and adolescent psychiatry in an historical and organisational perspective. It deals with some current advances and discussions with regard to technical aspects: indication, frame and process as well as extensions of technique, that will raise weaknesses in questions about training in psychotherapy.

Pharmacokinetic-pharmacodynamic model for spiramycin in staphylococcal mastitis.

Simultaneous pharmacokinetic-pharmacodynamic (PK/PD) modelling for spiramycin in staphylococcal infections of the mammary gland of cows was used to predict the efficacy of spiramycin. A differential equation derived from the Zhi model was fitted to an in vitro killing curve and post-antibiotic effect determination. A seven-compartment PK model, in which 4 compartments representing each quarter of the mammary gland which was considered to be the effect compartment, was included. The PD model linked to the PK model was able to describe the in vivo spiramycin effect against Staphylococcus aureus. The parameters calculated from in vitro data predicted a rapid decrease for the first 12-24 h, and regrowth within 72 h following the treatment, whereas in vivo the bacterial effect was much less after 24 h than that predicted by the in vitro data. PK/PD modelling permitted the simulation of various doses to optimize the efficacy of the antibiotic, taking into account such dynamic parameters as bacterial growth rate constant, bacterial killing rate constant and the Michaelis-Menten type saturation constant. An optimal dosage regimen of 20000 IU/kg per day for 3 days was predicted for the treatment of Staphylococcus aureus mastitis.

[Bactericidal effect of colistin on Escherichia coli. Model and simulation or the pharmacokinetic-pharmacodynamic relation for prediction of efficacy in veterinary antibiotic therapy]. / Effet bactéricide de la colistine vis-à-vis d'Escherichia coli. Modélisation et simulation de la relation pharmacocinétique-pharmacodynamique pour la prédiction de l'efficacité en antibiothérapie vétérinaire.

Pharmacodynamics studies consider three main parameters: the size of the bacterial population, the concentration of the antibiotic and the duration of its action. The pharmacodynamic characteristics of colistin were studied in vitro with Escherichia coli. The bacterial kinetics were fitted using differential equations. The mathematical model gave qualitative and quantitative information about the characteristics of the antibiotic-bacteria association. Above all, when linked to a pharmacokinetic model, the model permitted the prediction of the drug's efficiency. Simulations of various dosage levels in which the administration route, dose size, or interval between doses varied, permitted a more rational optimization than a prediction of efficacy based on the time taken to achieve antibiotic plasmatic concentrations above the minimal inhibitory concentration. Pharmacokinetic/pharmacodynamic modeling seems to be an interesting possibility for determining antibiotic dosing levels during the preclinical phase.

[Radiotherapy treatment of subfoveal retinal neovascularization related to age]. / Traitement par radiothérapie des néo-vaisseaux sous-rétiniens rétrofovéolaires liés à l'âge.

Thirty-three patients who underwent low dose of radiation therapy for subfoveal choroidal membranes were studied after a mean follow-up of 16 months. The evaluated parameters were the visual outcome and the choroidal neovascularization evolution. In this study, the efficacy of low-dose radiation delivered to the macular region as an alternative treatment in subfoveal membrane was limited.