Prevalence of severe cardiovascular disease in patients with schizophrenia.

OBJECTIVES: We assessed the prevalence of severe cardiovascular (CV) disease requiring hospitalization among patients with schizophrenia in France. METHOD: We included patients hospitalized with schizophrenia or psychotic disorder during 2015, in five French psychiatric hospitals. Patients with CV disease were defined as those with a correspondent ICD-10 code during a hospital stay in any general hospital, five years before or three years after the psychiatric hospitalization. CV disease included myocardial infarction (MI), stroke, heart failure (HF), coronary artery disease (CAD) or peripheral artery disease. Risk factors such as hypertension, obesity and diabetes were recorded. RESULTS: In total, 4424 patients with schizophrenia were included. Overall, 203 (4,6%) patients were diagnosed with CV disease, 93 (2.1%) with CAD, 86 (1.9%) with HF and 49 (1.1%) with stroke. The prevalence of hypertension, obesity and diabetes was 11.3%, 9.7% and 7.8%. The median (interquartile range) age of patients with MI and diabetes was 57 (49-70) and 56 (48-66) years. CONCLUSION: Patients with schizophrenia develop severe CV disease requiring hospitalization at an early age. These severe events are associated with a high prevalence of risk factors. Early screening and treatment of CV disease and risk factors is important to improve life expectancy and quality of life of these patients.

Adherence to fracture liaison service programs in patients over 70: the hidden part of the iceberg.

Significant dropout rates have been observed throughout Fracture Liaison Service (FLS) programs, especially for elderly patients. In an FLS program set up specifically for patients over 70, the non-initiation of osteoporosis treatment was the only factor associated with poor adherence to the program. Neither age nor frailty factors affected adherence. INTRODUCTION: FLS programs are considered the most effective interventions for secondary prevention of osteoporotic fractures. Our objective was to identify risk factors for non-adherence to an FLS program set up specifically for patients over 70. METHODS: Our multifaceted, intensive program included five appointments over a 2-year period. One hundred sixty-seven patients (mean age 83.5 years) who presented with a recent fragility fracture were enrolled. Multivariable analysis was conducted to determine whether the demographic, clinical, frailty, and osteoporotic risk factors of the patients influenced their adherence to the program. RESULTS: About half of the patients did not attend the follow-up visits. According to the regression analysis, non-initiation of osteoporosis treatment was associated with poor adherence to the program (aHR 3.66). Demographic, clinical, dwelling, frailty factors, osteoporotic risk factors, fracture type, or densitometric scores were not associated with adherence. The first self-reported reason for withdrawal was the difficulty of attending several follow-up visits, and the second was the feeling of not being concerned. CONCLUSION: We observed that non-initiation of osteoporosis treatment was the only factor correlated with non-adherence to an FLS program. Thus, neither age nor frailty factors should result in patients not being included in FLS. Beyond the necessity of the osteoporosis treatment, good patient understanding of the relevance of all the interventions included in the program is the key.

In vivo setup characterization for pulsed electromagnetic field exposure at 3 GHz.

An in vivo setup for pulsed electric field exposure at 3 GHz is proposed and characterized in this work. The exposure system allows far field, whole-body exposure of six animals placed in Plexiglas cages with a circular antenna. Chronic exposures under 18 W incident average power (1-4 kW peak power) and acute exposures under 56 W incident average power (4.7 kW peak power) were considered. Numerical and experimental dosimetry of the setup allowed the accurate calculation of specific absorption rate (SAR) distributions under various exposure conditions. From rat model numerical simulations, the whole-body mean SAR values were 1.3 W kg(-1) under chronic exposures and 4.1 W kg(-1) under acute exposure. The brain-averaged SAR value was 1.8 W kg(-1) and 5.7 W kg(-1) under chronic and acute exposure, respectively. Under acute exposure conditions, a 10 g specific absorption of 1.8 ± 1.1 mJ · kg(-1) value was obtained. With temperature rises below 0.8 °C, as measured or simulated on a gel phantom under typical in vivo exposures, this exposure system provides adequate conditions for in vivo experimental investigations under non-thermal conditions.

[Glance at tropical dermatitis]. / Coup d'œil sur une dermatite tropicale.

We report a case of a French soldier, among more than fifteen others, who looked for dermatitis occurred in Central African Republic revealing a lepidopterism. We detail the Anaphae venata etiologic agent, what to do diagnosis and treatment.

Thienyl-BOPHY dyes as promising templates for bulk heterojunction solar cells.

The synthesis and characterization of bis(difluoroboryl)-1,2-bis((1H-pyrrol-2-yl)methylene)hydrazone functionalized with two lateral vinyl-thienyl modules and exhibiting strong absorption in the 400-800 nm window in thin films are reported. Bulk heterojunction solar cells assembled with these dyes and a fullerene derivative (PC71BM), using very small quantities of the additive diiodooctane, give a power conversion efficiency as high as 4.3% with short-circuit current values of 10.9 mA cm(-2), an open-circuit voltage of 0.7 V and external quantum efficiencies higher than 70% over a broad range of wavelengths (580 to 720 nm).

[Recurrent deep vein thrombosis and myeloproliferative syndrom: emergence of JAK2 mutation five years after the initial event]. / Thromboses veineuses à répétition et syndrome myéloprolifératif : positivité secondaire d'une mutation JAK2 cinq ans après l'événement initial.

JAK 2 mutation is the molecular event responsible for 95% of polycythemia cases and 50% of thrombocythemia vera and myelofibrosis cases. It can be used as a tool for the diagnosis of myeloproliferative disorders. We report a case illustrating the fact that a negative result does not definitively eliminate the diagnosis. A 40-year old woman, with a medical history of familial deep vein thrombosis, developed thrombosis of the inferior vena cava with extension to the suprahepatic veins and pulmonary embolism. No constitutional or acquired thrombophilia was diagnosed; search for JAK 2 mutation was negative. The patient was treated with fluindione. Five years later, she relapsed with popliteo-femoral and vena cava deep vein thrombosis. The etiological work-up included a PET scan which revealed diffuse uptake in bones and suspected neoplasic bone marrow invasion. Progenitor cell cultures were positive and JAK 2 mutation was confirmed. The bone marrow aspirate had the cytologic appearance of a myeloproliferative disorder. This case illustrates the fact that JAK 2 mutation can be identified several years after onset of a latent myeloproliferative disorder. Cases with a high clinical likelihood should lead to renewed search for this mutation. Secondary discovery of this mutation can be explained by a higher proportion of mutation expressing clones.

Influence of paramagnetic melanin on the MRI contrast in melanoma: a combined high-field (11.7 T) MRI and EPR study.

Melanoma is the most dangerous form of skin cancer and its incidence is rising each year. Because the current methods of diagnosis based on the visual aspect of the tumor show limitations, several new techniques are emerging to help in this diagnosis, amongst which are magnetic resonance imaging (MRI) and electron paramagnetic resonance (EPR). The origin of the typical contrast pattern observable in melanoma in T1 - and T2 -weighted images remains to be elucidated and is a source of controversy. In addition, melanin could create sufficient magnetic inhomogeneities to allow its visualization on T2 *-weighted images using high-field MRI. In order to elucidate the possible role of melanin in the MRI contrast of melanoma, the present study was designed to correlate the paramagnetic content in melanin pigment to the contrast on T1 -, T2 - and T2 *-weighted images. MR images were obtained in vivo at 11.7 T using four types of experimental tumors with different pigmentations (B16, HBL, LND1 melanomas and KHT sarcomas). The paramagnetic content in melanin pigment was measured by EPR. No significant correlation was observed between the content in melanin and the relaxation times T1 , T2 and T2 *, emphasizing that the presence of pigment alone has negligible effect on the MRI contrast.

Electron paramagnetic resonance as a sensitive tool to assess the iron oxide content in cells for MRI cell labeling studies.

MRI cell tracking is a promising technique to track various cell types (stem cells, tumor cells, etc.) in living animals. Usually, cells are incubated with iron oxides (T(2) contrast agent) in order to take up the particles before being injected in vivo. Iron oxide quantification is important in such studies for validating the labeling protocols and assessing the dilution of the particles with cell proliferation. We here propose to implement electron paramagnetic resonance (EPR) as a very sensitive method to quantify iron oxide concentration in cells. Iron oxide particles exhibit a unique EPR spectrum, which directly reflects the number of particles in a sample. In order to compare EPR with existing methods (Perls's Prussian blue reaction, ICP-MS and fluorimetry), we labeled tumor cells (melanoma and renal adenocarcinoma cell lines) and fibroblasts with fluorescent iron oxide particles, and determined the limits of detection of the different techniques. We show that EPR is a very sensitive technique and is specific for iron oxide quantification as measurements are not affected by endogenous iron. As a consequence, EPR is well adapted to perform ex vivo analysis of tissues after cell tracking experiments in order to confirm MRI results.

[Deafness in adults. Study of practices in general medicine]. / Les surdités de l'adulte. Etude de pratiques en médecine générale.

INTRODUCTION: Deafness is a sensory disability responsible for communication disorder, sometimes impairing social life. In children, the hearing is an important concern for all stakeholders in early childhood (systematic neonatal screening, etc.). On the other hand, in the adult, it is rarely tested, and patients do consult when their audiometric status is already badly impaired. But their care is all the better if the deafness diagnosis is made early, as for the audio-prosthetic rehabilitation for example. Today, the general practitioner is the first link of the diagnostic and therapeutic management chain. The objective of this study was to evaluate the diagnostic practices of practitioners in front of deafness in adults. SUBJECTS AND METHODS: This prospective study included 74 practitioners based in "Ile de France" interviewed using a multiple choice questionnaire (MCQ) on otoscopic and audiometric diagnostics and a Script Concordance test (SC) on clinical adult deafness situations validated by a 5 experts panel. RESULTS: The obtained average score was 66.35% of correct answers to the MCQ and 47.76% to the SC. CONCLUSIONS: In our study, the surveyed practitioners showed a good level of otoscopic and audiometric diagnosis in the MCQ. However, their answers were not concordant with those of the expert panel in the SC. They have been particularly poorly performing on issues related to functional signs and their use in a given clinical situation, often driving to establish an otoscopic misdiagnosis while their diagnostic recognition of a pathological eardrum in the MCQ was rather good. These results reflect a lack of confidence in their otoscopic diagnosis related to the lack of knowledge of the causes of deafness in adults and their symptoms.

Cytogenetic studies in human cells exposed in vitro to GSM-900 MHz radiofrequency radiation using R-banded karyotyping.

It is important to determine the possible effects of exposure to radiofrequency (RF) radiation on the genetic material of cells since damage to the DNA of somatic cells may be linked to cancer development or cell death and damage to germ cells may lead to genetic damage in next and subsequent generations. The objective of this study was to investigate whether exposure to radiofrequency radiation similar to that emitted by mobile phones of second-generation standard Global System for Mobile Communication (GSM) induces genotoxic effects in cultured human cells. The cytogenetic effects of GSM-900 MHz (GSM-900) RF radiation were investigated using R-banded karyotyping after in vitro exposure of human cells (amniotic cells) for 24 h. The average specific absorption rate (SAR) was 0.25 W/kg. The exposures were carried out in wire-patch cells (WPCs) under strictly controlled conditions of temperature. The genotoxic effect was assessed immediately or 24 h after exposure using four different samples. One hundred metaphase cells were analyzed per assay. Positive controls were provided by using bleomycin. We found no direct cytogenetic effects of GSM-900 either 0 h or 24 h after exposure. To the best of our knowledge, our work is the first to study genotoxicity using complete R-banded karyotyping, which allows visualizing all the chromosomal rearrangements, either numerical or structural.

A confirmation study of Russian and Ukrainian data on effects of 2450 MHz microwave exposure on immunological processes and teratology in rats.

In a series of Russian and Ukrainian papers published from 1974-1986, it was reported that 30-day whole-body exposures to continuous-wave (CW) radiofrequency (RF) radiation at 2375 MHz and 5 W/m(2) disrupted the antigenic structure of rat brain tissue. The authors suggested that this action caused an autoimmune response in exposed animals. Moreover, these studies reported that blood serum from exposed rats injected into intact nonexposed female rats on the 10th day of pregnancy led to increased postimplantation embryo mortality and decreased fetus size and body weight. Because the results of these studies served in part as the basis for setting exposure limits in the former USSR, it was deemed necessary to perform confirmation studies, using modern dosimetric and biological methods. In our study, a new system was constructed to expose free-moving rats under far-field conditions. Whole-body and brain-averaged specific absorption rates (SARs) were calculated. All results, using ELISA and classic teratology end points, were negative in our laboratory. On the basis of this investigation, we conclude that, under these exposure conditions (2450 MHz, CW, 7 h/day, 30 days, 0.16 W/kg whole-body SAR), RF-radiation exposure had no influence on several immune and degenerative parameters or on prenatal development.

Determination of tumour hypoxia with [18F]EF3 in patients with head and neck tumours: a phase I study to assess the tracer pharmacokinetics, biodistribution and metabolism.

PURPOSE: The aim of this study was to assess the pharmacokinetics, biodistribution and metabolism of [(18)F]EF3, a labelled 2-nitroimidazole hypoxia marker, in ten patients with head and neck cancer. METHODS: [(18)F]EF3 was administered intravenously (group 1, n=5, mean dose+/-SD: 324+/-108 MBq; group 2, n=5, mean dose+/-SD: 1,134+/-138 MBq) to patients (nine male, one female). Blood and urine samples and whole-body PET scans were obtained from 20 s to 4-6 h. Radioactivity was determined in several regions of interest. RESULTS: No serious adverse event was reported. [(18)F]EF3 concentration in blood exhibited a bi-exponential decline. [(18)F]EF3 was mainly eliminated in the urine. By 7 h 40 min after injection, 53+/-14% of the injected dose was collected in the urine. There was no significant difference between the low- and high-dose groups. A progressive accumulation occurred also in the colon, indicating a hepatobiliary excretion. Except in organs involved in the elimination of [(18)F]EF3, the tumour-to-organ ratio remained close to or below unity in muscle, lungs, heart and brain at various times after injection. In one patient, tumour hypoxia was observed with a tumour-to-blood ratio ranging from 1.4 to 1.9. Last, [(18)F]EF3 remained very stable after injection, with percentage of native tracer above 87% in the serum and 84% in the urine. CONCLUSION: Administration of [(18)F]EF3 in head and neck cancer patients is feasible and safe. Uptake and retention in tumour was observed, indicating the presence of hypoxia.

Effect of GSM-900 and -1800 signals on the skin of hairless rats. I: 2-hour acute exposures.

PURPOSE: The acute influence on the skin of non-ionizing electromagnetic fields in the radiofrequency (RF) range used in mobile telephony has not been widely studied to date. The purpose of this work was to determine whether the cells of hairless rat skin are affected by acute local exposure to Global System for Mobile Communication: GSM-900 or -1800 RadioFrequency Radiation (RFR). MATERIALS AND METHODS: Hairless female rats were exposed or sham-exposed for 2 h to GSM-900 or -1800 signals, using a loop-antenna located on the right part of the rats' back. The local Specific Absorption rate (SAR) at skin level was ca. 5 W/kg (5.8+/-0.4 and 4.8+/-0.4 W/kg at 900 and 1800 MHz, respectively). A skin biopsy was done at the end of the experiment not only at the location of exposure, but also on the symmetrical part of the back. RESULTS: Analysis of skin sections using Hematoxylin Eosin Saffron (HES) coloration showed no difference in skin thickness or apparent cell toxicity (with no sign of cellular necrosis) among the animal groups. Histological analysis of the epidermis showed that the ratio between cells expressing the antigen Ki-67 (cellular proliferation marker) and the total number of cells remained within the range of normal proliferation ratio for the exposed side of the animal. No Ki-67 labelling was observed at the dermis level. Results on filaggrin, collagen and elastin levels also showed an insignificant influence of RFR. CONCLUSIONS: These results do not demonstrate any major physical and histological variations at skin level induced by RFR used in mobile telephony.

Effect of GSM-900 and -1800 signals on the skin of hairless rats. II: 12-week chronic exposures.

PURPOSE: The purpose of this work was to determine whether the cellular components of Hairless-rat skin are affected by a chronic local exposure to non-ionizing radiations of Global Mobile Phone System: GSM-900 or -1800 radiations at specific absorption rate (SAR) 2.5 and 5 W/kg. MATERIALS AND METHODS: A selected part of the right back of five-week old female hairless rats was exposed or sham exposed (n = 8) for 2 h per day, 5 days a week, for 12 weeks to GSM-900 or -1800 signals using a loop-antenna. At the end of the experiment, skin biopsies were taken. RESULTS: Analyses of skin sections using hematoxylin eosin saffron (HES) coloration showed no significant difference in skin thickness among the groups. Immunohistochemical analysis of basal lamella cells in radiofrequency radiation (RFR)-exposed epidermis showed that the ratio of the antigen Ki-67 (cellular proliferation marker) positive cells to total lamella cells remained within the range of the normal proliferation ratio. No significant differences in the level of filaggrin, collagen, and elastin were observed among the different groups. CONCLUSIONS: The results of this 12-week chronic study do not demonstrate major histological variations in the skin of hairless rats exposed to RFR used in mobile telephony (GSM-900 or -1800).

Microwave exposure of neuronal cells in vitro: Study of apoptosis.

PURPOSE: The aim of this study was to investigate microwave (MW) effects on neuronal apoptosis in vitro. MATERIALS AND METHODS: Human neuroblastoma cells SH-SY5Y were exposed to a 900 MHz global system for mobile communication (GSM) or continuous-wave (CW) radiofrequency fields for 24 h in a wire-patch cell. The specific absorption rates (SAR) used were 2 W/kg for CW and 0.25 W/kg average for GSM. During CW exposure, an increase of 2 degrees C was measured, and controls with cells exposed to 39 degrees C were then performed. Apoptosis rate was assessed immediately or 24 h after exposure using three methods: (i) 4',6-diamino-2-phenylindole (DAPI) staining; (ii) flow cytometry using double staining with TdT-mediated dUTP nick-end labeling (TUNEL) and propidium iodide (PI); and (iii) measurement of caspase-3 activity by fluorimetry. RESULTS: No statistically significant difference in the apoptosis rate was observed between sham and 24 h MW-exposed cells, either GSM-900 at an average SAR of 0.25 W/kg, or CW 900 MHz at a SAR of 2 W/kg, either 0 h or 24 h post-exposure. Furthermore, for CW-exposure, apoptosis rates were comparable between sham-, CW-, 37 degrees C- and 39 degrees C-exposed cells. All three methods used to assess apoptosis were concordant. CONCLUSION: These results showed that, under the conditions of the present experiment, MW-exposure (either CW or GSM-900) does not significantly increase the apoptosis rate in the human neuroblastoma cell line SH-SY5Y.

Preclinical validation of the hypoxia tracer 2-(2-nitroimidazol-1-yl)- N-(3,3,3-[(18)F]trifluoropropyl)acetamide, [(18)F]EF3.

The 2-nitroimidazole derivative 2-(2-nitroimidazol-1-yl)- N-(3,3,3-trifluoropropyl)acetamide (EF3) is a marker which forms adducts into hypoxic cells. Radiosynthesis of [(18)F]EF3 was recently performed by our group. Our aim was to study the pharmacokinetics, biodistribution, metabolism and specificity for hypoxia of [(18)F]EF3. MCa-4, SCC VII, NFSA, FSA, FSA II or Sa-NH tumour-bearing C3H mice were injected intravenously with [(18)F]EF3 and allowed to breathe air, 10% O(2) or carbogen until sacrifice 5-770 min after injection. Radioactivity was measured ex vivo in various organs, including urine and faeces. Selected organs were additionally processed to measure tracer metabolites with high-performance liquid chromatography. The half-life in blood was 73.9 min. [(18)F]EF3 was eliminated mainly via the kidneys, with 75% of the injected activity found in the urine by 12 h 50 min. The biodistribution was fast and homogeneous except in the brain and the bone, where it was significantly lower, and in the liver and the kidney, where it was significantly higher. In most organs, the exceptions being the gastrointestinal and urinary tract, tissue-to-blood ratios were below or close to unity. In tumours, a relative accumulation of the tracer was observed with time, which, at 220 min after injection, depended on tumour strain and oxygenation conditions, i.e. 10% O(2) significantly increased the tumour-to-muscle ratio whereas carbogen decreased it. [(18)F]EF3 was rapidly metabolised in the kidney and the liver. [(18)F]EF3 is a promising tracer for detection of tumour hypoxia. A phase I study in head and neck cancer patients is in progress at our institution.

Biodistribution, binding specificity and metabolism of [18F]fluoroethylflumazenil in rodents.

Pre-clinical studies were carried out in order to characterize in rodents the biodistribution, the binding specificity and the metabolism of [18F]Fluoroethylflumazenil ([18F]FEF), a potential candidate for in vivo imaging of the benzodiazepine receptors. In vivo competition with flumazenil indicates that [18F]FEF binds specifically to the benzodiazepine receptor in the brain. The accumulation of [18F]FEF was significantly lower than using [3H]Flumazenil. The rather low accumulation in the brain is due to a rapid metabolism of [18F]FEF in hydrophylic metabolites which cannot cross the blood brain barrier, and are rapidly eliminated in the urine. Inhibition of the metabolism by acetaminophen (chemically induced hepatitis) led to a significant increase of the radioactivity found in the circulating blood and in the brain, while these results were not observed using classical inhibitors of the cytochrome CYP450, cimetidine and ketoconazole.