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Biomedical subjects

Marc Labetoulle

Publications and source records attributed to Marc Labetoulle.

10 recordsLinked to original sources

[The effects of medications on the eyes].

The visual system is very sensitive to side effects of medicines, either regarding systematic complications of eye drops or ocular complications following oral or intravenous treatments. For the latter, ophthalmologic regular monitoring is mostly the best preventive measure since most of iatrogenic abnormalities are reversible after ruling out the treatment. However, some ocular complications are poorly reversible, as for example with antimalarial drugs or vigabatrin. Concerning systemic complications of ocular treatments, their risk is often underestimated, while the passage of drugs in the blood can sometimes reach similar rates than those observed after an oral administration, as it is the case with some beta-blockers ophthalmic solutions. It is also advisable to distrust overdoses, or accidental oral ingestions, of parasympatholytic mydriatics which can induce neurological and cardiac complications in children or in elderly.

Drug-Related Side Effects and Adverse Reactions↗

Activation of IFN pathways and plasmacytoid dendritic cell recruitment in target organs of primary Sjögren's syndrome.

Gene expression analysis of target organs might help provide new insights into the pathogenesis of autoimmune diseases. We used global gene expression profiling of minor salivary glands to identify patterns of gene expression in patients with primary Sjögren's syndrome (pSS), a common and prototypic systemic autoimmune disease. Gene expression analysis allowed for differentiating most patients with pSS from controls. The expression of 23 genes in the IFN pathways, including two Toll-like receptors (TLR8 and TLR9), was significantly different between patients and controls. Furthermore, the increased expression of IFN-inducible genes, BAFF and IFN-induced transmembrane protein 1, was also demonstrated in ocular epithelial cells by quantitative RT-PCR. In vitro activation showed that these genes were effectively modulated by IFNs in salivary gland epithelial cells, the target cells of autoimmunity in pSS. The activation of IFN pathways led us to investigate whether plasmacytoid dendritic cells were recruited in salivary glands. These IFN-producing cells were detected by immunohistochemistry in all patients with pSS, whereas none was observed in controls. In conclusion, our results support the pathogenic interaction between the innate and adaptive immune system in pSS. The persistence of the IFN signature might be related to a vicious circle, in which the environment interacts with genetic factors to drive the stimulation of salivary TLRs.

Adult↗

Herpes simplex virus type 1 latently infected neurons differentially express latency-associated and ICP0 transcripts.

During the latent phase of herpes simplex virus type 1 (HSV-1) infection, the latency-associated transcripts (LATs) are the most abundant viral transcripts present in neurons, but some immediate-early viral transcripts, such as those encoding ICP0, have also been reported to be transcribed in latently infected mouse trigeminal ganglia (TG). A murine oro-ocular model of herpetic infection was used to study ICP0 gene expression in the major anatomical sites of HSV-1 latency, including the TG, superior cervical ganglion, spinal cord, and hypothalamus. An HSV-1 recombinant strain, SC16 110LacZ, revealed ICP0 promoter activity in several neurons in latently infected ganglia, and following infection with wild-type HSV-1 strain SC16, in situ hybridization analyses identified ICP0 transcripts in the nuclei of neurons at times consistent with the establishment of latency. Reverse transcription (RT)-PCR assays performed on RNA extracted from latently infected tissues indicated that ICP0 transcripts were detected in all anatomical sites of viral latency. Furthermore, quantitative real-time RT-PCR showed that neurons differentially expressed the LATs and ICP0 transcripts, with splicing of ICP0 transcripts being dependent on the anatomical location of latency. Finally, TG neurons were characterized by high-level expression of LATs and detection of abundant unspliced ICP0 transcripts, a pattern markedly different from those of other anatomical sites of HSV-1 latency. These results suggest that LATs might be involved in the maintenance of HSV-1 latency through the posttranscriptional regulation of ICP0 in order to inhibit expression of this potent activator of gene expression during latency.

Animals↗

Systemic adverse effects of topical ocular treatments.

Some eyedrops, gels or ointments may cause adverse effects as serious as those observed with systemic therapies. Because of their relatively poor penetration into eye tissue, ophthalmic drugs usually contain high concentrations of their active ingredient. Asking patients about these drugs to prevent interactions is useful when prescribing a new systemic treatment. Conversely, it is advisable to ask about ophthalmic drugs during the etiological investigation of possible iatrogenic effects.

Administration, Topical↗

Key points.

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Journal Article↗

HSV1 latency sites after inoculation in the lip: assessment of their localization and connections to the eye.

PURPOSE: To localize the sites of HSV1 latency in mice after a primary infection induced by injection into the lip and to assess their connection to the eye. METHODS: The SC16 strain of HSV1, or a recombinant virus containing the HSV1 latency-associated transcript (LAT)-promoter driving expression of the LacZ reporter gene, were injected into the left upper lip. Tissues from animals killed at 6, 28, 180, and 720 days postinoculation (dpi) were analyzed for LATs, either by in situ hybridization (ISH) or by identifying LAT-promoter-driven transgene expression. HSV1 antigens were detected by immunochemistry. RESULTS: At 28 dpi, all the neurologic structures that were acutely infected at 6 dpi exhibited a pattern of virus gene expression consistent with HSV1 latency--that is, LATs with no detectable HSV1 antigens. LAT staining differed among structures: intense and widespread within trigeminal neurons, intermediate within the sympathetic intermediolateral cell group of the spinal cord and the facial motor nucleus, and weak in other sites. Long-term expression of LATs (positive at 180 and 720 days) was observed only in tissues where the staining was intense or intermediate at 28 dpi. CONCLUSIONS: After inoculation into the upper lip of mice, HSV1 established latency in several nervous system structures that have direct or indirect connections with ocular tissues. These results suggest that after an oral primary infection, the most frequent in humans, HSV1 may establish latency in several sites connected to the eye and may finally result in herpetic ocular disease involving the cornea, the iris, or even the retina.

Animals↗

[Ocular infections of the elderly].

A CLINICAL ASPECT DEPENDING ON THE PHYSIOPATHOGENESIS: Ocular infections are a frequent motive for ophthalmological consultations in geriatric settings because of the mechanical factors related to age (modifications in palpebral dynamics and lacrymal function) and in local and general immune factors leading to the rapid and/or more severe development of infections. The mechanism of microbial contamination of the eye also determines the clinical damage: predominantly local (dirty hands, traumas) with involvement of the surface tissues (conjunctive and cornea) or general, hematogenic or neurogenic, frequently at the origin of more internal infections (iris, choroid, retina, optical nerve). CONJUNCTIVITIS AND KERATITIS: These provoke reddening of the eyes, tears and above all pain when the corneal epithelium is involved. Microbiological samples are useful in cases of severe, presumably infectious keratitis or conjunctivitis. Two emergency situations must be distinguished: any suspicion of herpes for which local corticosteroids are contraindicated and keratitis or conjunctivitis with the use of lenses, often due to Gram negative bacilli, amoeba or fungus, the treatment of which is intensive and the prognosis often severe. OPHTHALMOLOGICAL HERPES ZOSTER: The rapid diagnosis and introduction of efficient doses of antivirals reduces the initial pain, the ocular complications of herpes zoster and post-zoster pain. The latter, when it exists, requires specialized management. ACUTE UVEITIS: A context of intra-ocular inflammation in an elderly patient must always evoke a pseudo-uveitis syndrome, the principle cause of which is lymphoma. Conversely, an uveitis occurring in the days or weeks following ocular surgery, including cataract, must be considered as suggestive of a post-surgical infection and rapidly referred to a specialist. ACUTE DACRYOCYSTITIS: Is manifested by a hard and painful tumefaction below the internal angle of the eye. Following collection, it requires draining through an in incision in the skin, washing and packing of the sac, and systemic antibiotherapy. The preventive treatment of recurrences requires open dacryocystorhinostomy or via endonasal endoscopy.

Acute Disease↗

Non-preserved 1% lidocaine solution has less antibacterial properties than currently available anaesthetic eye-drops.

PURPOSE: Some anaesthetics inhibit bacterial growth, and thus may lead to low rates of positive cultures from bacterial keratitis. Antibacterial properties of lidocaine were compared with those of oxybuprocaine or tetracaine, either in current commercial eye lotions or in extemporaneous solutions. METHODS: Forty-eight bacterial strains were used to determine the minimum inhibitory and bactericidal concentrations of four commercial eye lotions containing oxybuprocaine or tetracaine, of a non-ophthalmic 1% lidocaine commercial solution and of extemporaneously prepared solutions of oxybuprocaine, tetracaine, lidocaine and benzalkonium. RESULTS: Most strains had their growth inhibited by 0.2% oxybuprocaine or 0.4% tetracaine, which corresponds to a 1/2 dilution of the commercial eye-drops. Bacterial growth was still observed with a 1% lidocaine solution. CONCLUSIONS: Currently available anaesthetic eye-drops that are used before corneal specimen collection may lead to false-negative bacterial cultures. Conversely, a non-preserved 1% lidocaine solution might be more appropriate in corneal specimen collection.

Anesthetics, Local↗

Phacoemulsification combined with silicone oil removal through the posterior capsulorhexis tear.

PURPOSE: To evaluate phacoemulsification combined with silicone oil removal through the posterior capsulorhexis tear. METHOD: The records of 20 patients with cataract after silicone oil repair of retinal detachment with giant retinal tear or complicated by proliferative vitreoretinopathy were reviewed. All eyes underwent phacoemulsification, posterior capsulorhexis, aspiration of silicone oil with an irrigation-aspiration hand piece, and intraocular lens implantation into the capsular bag. Lens calculation was based on the fellow eye. The mean follow-up period after cataract surgery was 15.4 months. RESULTS: There were three recurrences of retinal detachment (15%). Transient corneal edema was noted in two eyes. Unpredictable refraction was the main problem, but the myopic refractive error was <4.5 diopters in all cases. CONCLUSION: Cataract extraction combined with silicone oil removal is an effective technique.

Adolescent↗