Light-induced retinal damage using different light sources, protocols and rat strains reveals LED phototoxicity.

To save energy, the European directives from the Eco-design of Energy Using Products (2005/32/CE) have recommended the replacement of incandescent lamps by more economic devices such as Light Emitting Diodes (LEDs). However, the emission spectrum of these devices is enriched in blue radiations, known to be potentially dangerous to the retina. Recent studies showed that light exposure contributes to the onset of early stages of age-related macular degeneration (AMD). Here, we investigate, in albinos and pigmented rats, the effects of different exposure protocols. Twenty-four hours exposure at high luminance was compared to a cyclic (dark/light) exposure at domestic levels for 1week and 1month, using different LEDs (Cold-white, blue and green), as well as fluorocompact bulbs and fluorescent tubes. The data suggest that the blue component of the white-LED may cause retinal toxicity at occupational domestic illuminance and not only in extreme experimental conditions, as previously reported. It is important to note that the current regulations and standards have been established on the basis of acute light exposure and do not take into account the effects of repeated exposure.

Mouth self-examination in a population at risk of oral cancer.

BACKGOUND: Cancer of the oral cavity is a public health problem and many cases are not diagnosed until the disease has reached an advanced stage. The aim of this study was to initiate an educational programme in self-examination for patients at risk from oral cancer. METHODS: This quasi-experimental study set out to initiate an educational programme in self-examination for patients at risk from oral cancer, assessing the outcomes after three months. In individual 15-minute face-to-face sessions, patients were given information and training in oral cancer risk factors and then verbal instructions as how to carry out oral self-examination. Three months later, patients were interviewed by telephone and asked if they had carried out self-examination independently at home. The programme was evaluated by means of a health belief model questionnaire on perceived susceptibility (3 items), severity (8 items), benefits (4 items), barriers (8 items) and efficacy (6 items). RESULTS: Eighty-six patients (37 females [43.1%] and 49 males [56.9%]) with a mean age of 58.60±10.7 completed the oral self-examination programme. Logistic regression analysis indicated that patients who felt themselves subject to susceptibility (OR: 0.03 95% CI: 0.0-0.86; p<0.04), severity (OR 0.23 95% 0.08-0.68; p<0.008) and benefits (OR 0.11 95% 0.02-0.63; p<0.013) were more likely to perform self-examination. CONCLUSIONS: Training programmes in oral self-examination are needed to decrease morbidity and mortality from oral cancer.

Assessment of self-reported sleep disturbance and psychological status in patients with burning mouth syndrome.

OBJECTIVES: To investigate the quality of sleep of patients with primary burning mouth syndrome (BMS) compared with a control group. METHODS: A total of 70 patients with primary BMS and 70 control subjects were enrolled in the study. The severity of pain was evaluated with a Visual Analogue Scale (VAS). Four validated questionnaires were used to investigate the psychological profile of each patient: the Hospital Anxiety and Depression Scale, the Oral Health Impact Profile-14 (OHIP-14), the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (EES). RESULTS: Poor sleep quality was present in 67.1% patients with BMS vs. 17.1% in control subjects (P ≤ 0.001). For patients with BMS, total data resulting from the PSQI correlated with results obtained by the EES (P ≤ 0.001), VAS pain (P ≤ 0.001), localization (P = 0.01), HAD-A (P = 0.001) and HAD-D (P = 0.001). Logistic regression analysis showed that an increase of one point in each depression score (HAD-D) made the chances of PSQI 1.26 times more likely, with a 95% confidence interval (CI = 1.03-1.55). CONCLUSIONS: Patients with primary BMS exhibited significant decreases in sleep quality compared with the control group.

Long-term efficacy of ciliary muscle gene transfer of three sFlt-1 variants in a rat model of laser-induced choroidal neovascularization.

Inhibition of vascular endothelial growth factor (VEGF) has become the standard of care for patients presenting with wet age-related macular degeneration. However, monthly intravitreal injections are required for optimal efficacy. We have previously shown that electroporation enabled ciliary muscle gene transfer results in sustained protein secretion into the vitreous for up to 9 months. Here, we evaluated the long-term efficacy of ciliary muscle gene transfer of three soluble VEGF receptor-1 (sFlt-1) variants in a rat model of laser-induced choroidal neovascularization (CNV). All three sFlt-1 variants significantly diminished vascular leakage and neovascularization as measured by fluorescein angiography (FA) and flatmount choroid at 3 weeks. FA and infracyanine angiography demonstrated that inhibition of CNV was maintained for up to 6 months after gene transfer of the two shortest sFlt-1 variants. Throughout, clinical efficacy was correlated with sustained VEGF neutralization in the ocular media. Interestingly, treatment with sFlt-1 induced a 50% downregulation of VEGF messenger RNA levels in the retinal pigment epithelium and the choroid. We demonstrate for the first time that non-viral gene transfer can achieve a long-term reduction of VEGF levels and efficacy in the treatment of CNV.

Non-viral gene therapy for GDNF production in RCS rat: the crucial role of the plasmid dose.

Glial cell line-derived neurotrophic factor (GDNF) is one of the candidate molecules among neurotrophic factors proposed for a potential treatment of retinitis pigmentosa (RP). It must be administered repeatedly or through sustained releasing systems to exert prolonged neuroprotective effects. In the dystrophic Royal College of Surgeon's (RCS) rat model of RP, we found that endogenous GDNF levels dropped during retinal degeneration time course, opening a therapeutic window for GDNF supplementation. We showed that after a single electrotransfer of 30 µg of GDNF-encoding plasmid in the rat ciliary muscle, GDNF was produced for at least 7 months. Morphometric, electroretinographic and optokinetic analyses highlighted that this continuous release of GDNF delayed photoreceptors (PRs) as well as retinal functions loss until at least 70 days of age in RCS rats. Unexpectedly, increasing the GDNF secretion level accelerated PR degeneration and the loss of electrophysiological responses. This is the first report: (i) demonstrating the efficacy of GDNF delivery through non-viral gene therapy in RP; (ii) establishing the efficacy of intravitreal administration of GDNF in RP associated with a mutation in the retinal pigment epithelium; and (iii) warning against potential toxic effects of GDNF within the eye/retina.

Benefits of Ophdiat, a telemedical network to screen for diabetic retinopathy: a retrospective study in five reference hospital centres.

AIM: One objective of Ophdiat, a telemedical network using digital non-mydriatic cameras in Ile-de-France, is to develop a comprehensive screening programme that provides access to annual fundus examinations to all diabetic patients. The aim of this study was to evaluate the benefits of this programme in a hospital setting. METHODS: A retrospective analysis of 500 case reports of diabetic patients hospitalized before and after Ophdiat setup was performed in five reference hospital centres. At each centre, 100 case reports (50 before, 50 after) of patients aged greater than 18 years, hospitalized for their annual check-up, with no known diabetic retinopathy (DR) before hospitalization and with the last fundus examination performed greater than 11 months previously, were randomly selected. The primary endpoint was the proportion of patients whose fundus examinations were performed during hospitalization; secondary endpoints were the number of cases of DR found and the time taken by ophthalmologists to make the diagnosis. RESULTS: The mean proportion of patients with fundus examinations was 50.4% and 72.4% before and after, respectively, Ophdiat (P<0.01). The prevalence of DR was 11.1% before and 12.7% after (not significant). The mean time taken by an ophthalmologist per diagnosis of DR was 0.90 half-day before and 0.32 half-day after Ophdiat. CONCLUSION: This evaluation shows that Ophdiat, combined with the availability of modern and effective devices, has improved DR screening in diabetology departments in hospitals. Additional human resources would certainly ensure more effective use of the system.

[Drug delivery systems for intraocular applications]. / Dispositifs de délivrance de principes actifs pour des applications ophtalmologiques.

Numerous drug delivery systems (DDSs) can be used as intraocular tools to provide a sustained and calibrated release for a specific drug. Great progress has been made on the design, biocompatibility, bioavailability, and efficacy of DDSs. Although several of them are undergoing clinical trials, a few are already on the market and could be of a routine use in clinical practice. Moreover, miniaturization of the implants makes them less and less traumatic for the eye tissues and some DDSs are now able to target certain cells or tissues specifically. An overview of ocular implants with therapeutic application potentials is provided.

Non-viral ocular gene therapy: potential ocular therapeutic avenues.

Non-viral vectors for potential gene replacement and therapy have been developed in order to overcome the drawbacks of viral vectors. The diversity of non-viral vectors allows for a wide range of various products, flexibility of application, ease of use, low-cost of production and enhanced "genomic" safety. Using non-viral strategies, oligonucleotides (ODNs) can be delivered naked (less efficient) or entrapped in cationic lipids, polymers or peptides forming slow release delivery systems, which can be adapted according to the organ targeted and the therapy purposes. Tissue and cell internalization can be further enhanced by changing by physical or chemical means. Moreover, a specific vector can be selected according to disease course and intensity of manifestations fulfilling specific requirements such as the duration of drug release and its level along with cells and tissues specific targeting. From accumulating knowledge and experience, it appears that combination of several non-viral techniques may increase the efficacy and ensure the safety of these evolving and interesting gene therapy strategies.

Delivery of antisense oligonucleotide to the cornea by iontophoresis.

We wished to evaluate the potential of iontophoresis to promote the delivery of antisense oligonucleotides (ODN) directed at the vascular endothelial growth factor (VEGF)-R2 receptor (KDR/Flk) to the cornea of the rat eye. Fluorescence (CY5)-labeled ODNs in phosphate-buffered saline (PBS) (20 microM) were locally administered to rat eyes, and their fate within the anterior segment was studied. Thirty-four male, 5-week-old Wistar rats were used for all experiments. The rats were divided in four groups. In group I (12 rats, 12 eyes), the ODNs (20 microM) were delivered by iontophoresis (300 microA for 5 minutes) using a specially designed corneal applicator. In group II (12 rats, 12 eyes), the ODNs (20 microM) were delivered using the same applicator, but no electrical current was applied. In group III (6 rats, 6 eyes), a corneal neovascular reaction was induced prior to the application of ODNs (20 microM), and iontophoresis electrical current was delivered as for group I rats. Group IV (4 rats, 4 eyes) received ODN (60 microM) iontophoresis application (300 microA for 5 minutes) and were used for ODN integrity studies. The animals were killed 5 minutes, 90 minutes, and 24 hours after a single ODN application and studied. Topically applied ODNs using the same iontophoresis applicator but without current do not penetrate the cornea and remain confined to the superficial epithelial layer. ODNs delivered with transcorneoscleral iontophoresis penetrate into all corneal layers and are also detected in the iris. In corneas with neovascularization, ODNs were particularly localized within the vascular endothelial cells of the stroma. ODNs extracted from eye tissues 24 hours after iontophoresis remained unaltered. The iontophoresis current did not cause any detectable ocular damage under these conditions. Iontophoresis promotes the delivery of ODNs to the anterior segment of the eye, including all corneal layers. Iontophoresis of ODNs directed at VEGF-R2 may be used for the design of specific antiangiogenic strategy in diseases of the cornea.

Emergency preparedness and response in Israel during the Gulf War.

We examined the effect of the emergency response on medical and public health problems during the 1991 Gulf War in Israel. On the first day of the conflict, the number of deaths from suffocation, asphyxiation, aspiration, myocardial infarction, cardiac arrest, and cerebrovascular accident increased abruptly, as did the number of sudden deaths associated with the use of tight-fitting masks with filters in sealed rooms. Much of the excess risk for death from cardiorespiratory complications during the first alert may have been a consequence of its duration (140 minutes). Mass evacuation and concrete buildings are believed to have kept the death toll from trauma down, and mask use may have protected against facial and upper-airway injuries. Falls and hip fractures, airway irritation from exposure to bleach, carbon monoxide intoxication from open kerosene heaters in sealed rooms, and self-injection with atropine syringes were also noted. A measles epidemic and increased death rates from automobile crashes were other preventable causes of death. Protection against biological warfare was limited to surveillance of trends for pneumonia and gastroenteritis. Emergency planners failed to anticipate the need for better mask fit, hands-on training in the use of masks, and special guidelines for older persons to prevent deaths from suffocation and other cardiovascular-respiratory problems in the first minutes of use. If masks are to be distributed as a protection against chemical warfare, a simpler model including the use of shrouds for whole-body skin protection might help avoid cardiorespiratory complications. Public health problems not adequately dealt with in the predisaster period are apt to emerge with greater severity during a crisis.

Emergency preparedness and response in Israel during the Gulf War.

We examined the effect of the emergency response on medical and public health problems during the 1991 Gulf War in Israel. On the first day of the conflict, the number of deaths from suffocation, asphyxiation, aspiration, myocardial infarction, cardiac arrest, and cerebrovascular accident increased abruptly, as did the number of sudden deaths associated with the use of tight-fitting masks with filters in sealed rooms. Much of the excess risk for death from cardiorespiratory complications during the first alert may have been a consequence of its duration (140 minutes). Mass evacuation and concrete buildings are believed to have kept the death toll from trauma down, and mask use may have protected against facial and upper-airway injuries. Falls and hip fractures, airway irritation from exposure to bleach, carbon monoxide intoxication from open kerosene heaters in sealed rooms, and self-injection with atropine syringes were also noted. A measles epidemic and increased death rates from automobile crashes were other preventable causes of death. Protection against biological warfare was limited to surveillance of trends for pneumonia and gastroenteritis. Emergency planners failed to anticipate the need for better mask fit, hands-on training in the use of masks, and special guidelines for older persons to prevent deaths from suffocation and other cardiovascular-respiratory problems in the first minutes of use. If masks are to be distributed as a protection against chemical warfare, a simpler model including the use of shrouds for whole-body skin protection might help avoid cardiorespiratory complications. Public health problems not adequately dealt with in the predisaster period are apt to emerge with greater severity during a crisis.

Radon exposures in a Jerusalem public school.

In December 1995, ambient radon levels exceeding 10,000 Bq/m3 were measured in a basement shelter workroom of a multilevel East Talpiot, Jerusalem, public elementary school (six grades, 600 students). The measurements were taken after cancers (breast and multiple myeloma) were diagnosed in two workers who spent their workdays in basement rooms. The school was located on a hill that geologic maps show to be rich in phosphate deposits, which are a recognized source for radon gas and its daughter products. Levels exceeding 1000,000 Bq/m3 were measured at the mouth of a pipe in the basement shelter workroom, the major point of radon entry. The school was closed and charcoal and electret ion chamber detectors were used to carry out repeated 5-day measurements in all rooms in the multilevel building over a period of several months. Radon concentrations were generally higher in rooms in the four levels of the building that were below ground level. There were some ground-level rooms in the building in which levels reached up to 1300 Bq/m3. In rooms above ground level, however, peak levels did not exceed 300 Bq/m3. Exposure control based on sealing and positive pressure ventilation was inadequate. These findings suggested that radon diffused from highly contaminated basement and ground-floor rooms to other areas of the building and that sealing off the source may have led to reaccumulation of radon beneath the building. Later, subslab venting of below-ground radon pockets to the outside air was followed by more sustained reductions in indoor radon levels to levels below 75 Bq/m3. Even so, radon accumulated in certain rooms when the building was closed. This sentinel episode called attention to the need for a national radon policy requiring threshold exposure levels for response and control. A uniform nationwide standard for school buildings below 75 Bq/m3 level was suggested after considering prudent avoidance, the controversies over risk assessment of prolonged low-level exposures in children, and the fact that exposures in most locations in the Talpiot school could be reduced below this level. Proposal of this stringent standard stimulated the search for a strategy of risk control and management based on control at the source. This strategy was more effective and probably more cost effective than one based on suppression of exposure based on sealing and ventilation. Because many Israeli areas and much of the West Bank area of the Palestinian National Authority sit on the same phosphate deposits, regional joint projects for surveillance and control may be indicated.

Chrysotile and crocidolite asbestos in Israel: uses, exposures and risks.

Importation of raw asbestos (90% chrysotile; 10% crocidolite) for manufacture of cement products and other uses, including friction materials and spraying, had dropped to under 3000 tons by 1993 from a peak of 10,000 tons per annum in the late 1970s. Drops in use, manufacture, persons exposed in manufacture and measured exposure levels followed heightened public concern over the carcinogenic effects of asbestos products, despite a relatively high worker exposure standard of 400,000 f/m3. The atypically low ratio of reported deaths from lung cancer compared to mesothelioma in asbestos cement workers up to 1992 (1:2.5) is suggested to be a consequence of low baseline risks for lung cancer mortality in Israel and dropping smoking levels. Exposure to asbestos use and asbestos in place remain, but total risk should drop after 2010 if imports continue to drop. These projections may be altered by trade between Israel and its neighbors following peace agreements. Reductions in risk will have resulted from reduction in exposure brought about by reductions in manufacture and use.

[Nuclear magnetic resonance. Applications to medicine and biology (author's transl)]. / La résonance magnétique nucléaire. Ses applications á la médecine et á la biologie.

Nuclear magnetic resonance (NMR) is a non-invasive exploratory technique based on a principle radically different from those of radiography, radionuclide exploration and ultrasonography. Signals coming from atomic nuclei and reflecting their density and chemical/biochemical environment are collected, thus providing information of the physiological and pathological state of tissues. The technique has multiple applications, either practical (tomographic imaging of the brain, thyroid gland and liver) or in the field of research, e.g. investigating ischaemic myocardial areas and pathological fluid composition, measuring intracellular pH, diagnosing the nature of a tumour and, broadly speaking, understanding the biochemical changes associated with malignant degeneration.