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Oculopharyngeal muscular dystrophy (OPMD) is mainly characterized by ptosis and dysphagia. The genetic cause is a short expansion of a (GCN)10 repeat encoding for polyalanine in the poly(A) binding protein nuclear 1 (PABPN1) gene to (GCN)12–17 repeats. The (GCN)11/Ala11 allele has so far been described to be either a polymorphism or a recessive allele with no effect on the phenotype in the heterozygous state. Here we report the clinical and histopathological phenotype of a patient carrying a single (GCN)11/Ala11 heterozygous allele and presenting an atypical form of OPMD with dysphagia and late and mild oculomotor symptoms. Intranuclear inclusions were observed in his muscle biopsy. This suggests a dominant mode of expression of the (GCN)11/Ala11 allele associated with a partial penetrance of OPMD.

ABSTRACTThe diagnosis of acute otitis media (AOM) is often difficult, depending heavily on the experience and skills of the examiner. However, it is important to identify episodes of AOM that involve the risk of complications and to treat these episodes appropriately. The present study was performed in order to evaluate the use of a rapid antigen assay for Streptococcus pneumoniae, the Binax NOW test, as a diagnostic tool in patients with severe AOM and associated complications. The study included 70 patients with 74 episodes of AOM, 18 of them with complications. Cultures, Binax NOW tests, and a PCR assay were performed on nasopharyngeal secretions, middle ear fluid, and in some cases mastoid bone, cerebrospinal fluid, and urine. According to culture and PCR of the middle ear fluid, 30 (41%) of the episodes were caused by S. pneumoniae. The Binax NOW test was positive in 24 of these episodes (80%). It identified pneumococcal AOM independent of antibiotic treatment, and it was easily adapted to bone tissue. The test yielded sensitivity, specificity, and positive and negative predictive values for middle ear specimens of 85%, 100%, 100%, and 89%, respectively. The corresponding positive and negative values for predicting the bacterial etiology with nasopharyngeal secretions were 51% and 75%. This study showed that the Binax NOW test is a useful diagnostic tool for patients with severe AOM with or without complications.

Among the different mechanisms underlying opioid tolerance, receptor desensitization would represent a major cellular adaptation process in which the role of receptor internalization is still a matter of debate. In the present study, we examined desensitization of the human delta-opioid receptor (hDOR) produced by endogenous opioid peptides Leu-enkephalin (Tyr-Gly-Gly-Phe-Leu) and Met-enkephalin (Tyr-Gly-Gly-Phe-Met), and the contribution of internalization in this process. Results obtained with natural peptides were compared with those produced by a synthetic opioid agonist, SNC-80 [(+)-4-[(alphaR)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide). After a 30-min treatment, we observed a different regulation of hDOR between agonists. SNC-80 produced a stronger and faster desensitization and was associated with a loss of opioid binding sites by 50%. SNC-80 also caused a marked hDOR down-regulation by 30% as observed by Western blot. Immunocytochemistry revealed that SNC-80 induced a complete redistribution of hDOR from cell surface into intracellular compartments, whereas a partial internalization was visualized upon enkephalin exposure. In contrast, a stronger hDOR recycling and resensitization were measured after enkephalin treatment compared with SNC-80. These data strongly suggested a differential sorting of the internalized receptors caused by enkephalins and SNC-80 that was further confirmed by chloroquine as a lysosomal degradation blocker and monensin as a recycling endosome inhibitor. Finally, by preventing hDOR internalization with 0.5 M sucrose, we demonstrated that hDOR internalization contributes partially to desensitization. In conclusion, hDOR desensitization depends both on its internalization and its sorting either to the recycling pathway or to lysosomes.

In spite of extensive self-regulation of the fragrance industry, fragrance ingredients are still major causes of allergic contact dermatitis. There are indications that the problem is increasing in some countries, and that many nonregulated compounds are involved in the development of allergies. The use of essential oils in fragrance compounds might add both allergenic and carcinogenic compounds to a product and the exact composition of such ingredients is difficult to control. Herein, we propose a simple strategy to decrease the risk of adverse effects of fragrance ingredients in cosmetic products. This strategy consists of four major steps: (1) limit the concentration of fragrance compound in the products, (2) follow legislation and guidelines, (3) limit the concentration of a number of well-known sensitizing fragrance chemicals, and (4) limit the concentration of essential oils and materials with unknown composition. The strategy is discussed as an alternative to animal testing and in relation to other more resource-demanding approaches to the same problem.