La planification de sortie des personnes âgées hospitalisées dans un service de médecine

Contexte: la planification infirmière de sortie des personnes âgées est une composante importante des soins pour assurer une transition optimale entre l'hôpital et la maison. Beaucoup d'événements indésirables peuvent survenir après la sortie de l'hôpital. Dans une perspective de système de santé, les facteurs qui augmentent ce risque incluent un nombre croissant de patients âgés, l'augmentation de la complexité des soins nécessitant une meilleure coordination des soins après la sortie, ainsi qu'une augmentation de la pression financière. Objectif: évaluer si les interventions infirmières liées à la planification de sortie chez les personnes âgées et leurs proches aidants sont prédictives de leur perception d'être prêts pour le départ, du niveau d'anxiété du patient le jour de la sortie de l'hôpital et du nombre de recours non programmé aux services de santé durant les trente jours après la sortie. Méthode: le devis est prédictif corrélationnel avec un échantillon de convenance de 235 patients. Les patients âgés de 65 ans de quatre unités d'hôpitaux dans le canton de Vaud en Suisse ont été recrutés entre novembre 2011 et octobre 2012. Les types et les niveaux d'interventions infirmières ont été extraits des dossiers de soins et analysés selon les composantes du modèle de Naylor. La perception d'être prêt pour la sortie et l'anxiété ont été mesurées un jour avant la sortie en utilisant l'échelle de perception d'être prêt pour la sortie et l'échelle Hospital Anxiety and Depression. Un mois après la sortie, un entretien téléphonique a été mené pour évaluer le recours non programmé aux services de santé durant cette période. Des analyses descriptives et un modèle randomisé à deux niveaux ont été utilisés pour analyser les données. Résultats: peu de patients ont reçu une planification globale de sortie. L'intervention la plus fréquente était la coordination (M = 55,0/100). et la moins fréquente était la participation du patient à la planification de sortie (M = 16,1/100). Contrairement aux hypothèses formulées, les patients ayant bénéficié d'un plus grand nombre d'interventions infirmières de préparation à la sortie ont un niveau moins élevé de perception d'être prêt pour le départ (B = -0,3, p < 0,05, IC 95% [-0,57, -0,11]); le niveau d'anxiété n'est pas associé à la planification de sortie (r = -0,21, p <0,01) et la présence de troubles cognitifs est le seul facteur prédictif d'une réhospitalisation dans les 30 jours après la sortie de l'hôpital ( OR = 1,50, p = 0,04, IC 95% [1,02, 2,22]). Discussion: en se focalisant sur chaque intervention de la planification de sortie, cette étude permet une meilleure compréhension du processus de soins infirmiers actuellement en cours dans les hôpitaux vaudois. Elle met en lumière les lacunes entre les pratiques actuelles et celles de pratiques exemplaires donnant ainsi une orientation pour des changements dans la pratique clinique et des recherches ultérieures. - Background: Nursing discharge planning in elderly patients is an important component of care to ensure optimal transition from hospital to home. Many adverse events may occur after hospital discharge. From a health care system perspective, contributing factors that increase the risk of these adverse events include a growing number of elderly patients, increased complexity of care requiring better care coordination after discharge, as well as increased financial pressure. Aim: To investigate whether older medical inpatients who receive comprehensive discharge planning interventions a) feel more ready for hospital discharge, b) have reduced anxiety at the time of discharge, c) have lower health care utilization after discharge compared to those who receive less comprehensive interventions. Methods: Using a predictive correlational design, a convenience sample of 235 patients was recruited. Patients aged 65 and older from 4 units of hospitals in the canton of Vaud in Switzerland were enrolled between November 2011 and October 2012. Types and level of interventions were extracted from the medical charts and analyzed according to the components of Naylor's model. Discharge readiness and anxiety were measured one day before discharge using the Readiness for Hospital Discharge Scale and the Hospital Anxiety and Depression scale. A telephone interview was conducted one month after hospital discharge to asses unplanned health services utilization during this follow-up period. Descriptive analyses and a two- level random model were used for statistical analyses. Results: Few patients received comprehensive discharge planning interventions. The most frequent intervention was Coordination (M = 55,0/100) and the least common was Patient participation in the discharge planning (M = 16,1/100). Contrary to our hypotheses, patients who received more nursing discharge interventions were significantly less ready to go home (B = -0,3, p < 0,05, IC 95% [-0,57, -0,11]); their anxiety level was not associated with their readiness for hospital discharge (r = -0,21, p <0,01) and cognitive impairment was the only factor that predicted rehospitalization within 30 days after discharge ( OR = 1,50, p = 0,04, IC 95% [1,02, 2,22]). Discussion: By focusing on each component of the discharge planning, this study provides a greater and more detailed insight on the usual nursing process currently performed in medical inpatients units. Results identified several gaps between current and Best practices, providing guidance to changes in clinical practice and further research.

Analysis of photoreceptor abnormality in GUCY2D E837D/R838S transgenic pigs

Purpose: We generated genetically engineered pigs expressing the human dominant GUCY2DE837D/R838S allele to modelize cone dystrophy. After a functional follow-up showing reduced photopic ERG responses (ARVO 2011), we analyzed the eyes by immunohistochemistry and revealed retinal modifications in the transgenic group. Methods: Lentiviral vectors encoding the human double mutant GUCY2DE837D/R838S cDNA under the control of a portion of the pig arrestin-3 promoter (Arr3) were produced and used for lentiviral-mediated transgenesis in pigs. Animals were regularly submitted to behavioral and functional investigations and were sacrificed at 4, 7, 15 and 18 months of age for histological and RT-PCR analyses. Retinal markers were used to evaluate the retinal status of eleven transgenic pigs and 6 non-transgenic controls. The expression of the mutant cDNA was also assayed by RT-PCR. Results: A significant increase in the number of displaced nuclei in the outersegment layer is observed in transgenic animals compared to control animals independently of their age. Part of these nuclei originate from cones as demonstrated by colocalization with cone markers. No significant change in the ONL thickness (central and peripheral retina) was measured between 4 and 18 months of age, showing a slow progression of the disease in the transgenic pigs within this time-frame. Conclusions: Arr3-GUCY2DE837D/R838S pigs show signs of retinal abnormality with slow progression which parallels the loss of photopic function. Further characterization of this model should help to elucidate the molecular mechanisms underlying the disease evolution.

Late Onset Cystoid Macular Oedema Following Surgery for Radiation Induced Cataract in Patient With Retinoblastoma

Purpose: Cystoid macular oedema (CMO) is a very rare condition following cataract surgery in paediatric population. Nevertheless, we report a case series of patients with radiation induced cataract after retinoblastoma (Rb) treatment that underwent cataract surgery and developed subsequently late onset CMO. Methods: Between January 1984 and December 2009, 25 consecutive eyes (25 patients) with Rb presented with radiation induced cataract surgery at the Jules Gonin Eye Hospital. Sixteen eyes (16 patients) had prior radiation induced retinopathy and maculopathy (IRM). Out of these, 3 eyes (3 patients) developed CMO after cataract surgery. Results: One eye had Rb stage B, and 2 eyes had stage D International classification. All of them developed IRM following brachytherapy and/or external beam irradiation. Patients underwent phako-aspiration and in bag intraocular lens implantation after IRM had resolved. Mean age at cataract surgery was 10.7 ± 2.8 (SEM) (range 5-14) years old. Mean time between resolution of IRM and cataract surgery was 76.0 ± 27.2 (SEM) (range 24-116) months. Mean time of onset CMO after cataract surgery was 81.0 ± 34.4 (SEM) (range 13-124) months. There was no other underlying vascular or tractional factor for CMO development. All of them were treated with a combination of oral carbonic anhydrase inhibitor, topical steroid and topical non-steroid. Mean macular thickness pre-, during-, and post CMO were 134.0 ± 10.3, 298.0 ± 37.1, and 154.0 ± 4.0 (SEM) µm, respectively. Mean best corrected visual acuity pre-, during-, and post CMO were 0.31 ± 0.19, 0.46 ± 0.12, and 0.34 ± 0.18 (SEM) LogMAR, respectively. Mean time for CMO reabsorption was 17.0 ± 9.8 (SEM) months. Conclusions: To the best of our knowledge, CMO following paediatric cataract surgery is a very uncommon condition. Moreover, late onset CMO after phako-aspiration for radiation induced cataract in Rb patients has never been described. It is a rare complication but can be treated successfully.

Bilateral Uveal Pigmented Alterations With Remarkable Evolution: Long Term Follow-Up in a Case of Possible Bilateral Diffuse Uveal Melanocytic Proliferation

Purpose: to describe a case of probable bilateral diffuse uveal melanocytic proliferation (BDUMP) with scleral involvement, free from systemic malignancies and cataract. Methods: fifty months of follow up with recurrent complete ophthalmological examinations, including fundus photography, fluorescein/indocyanine green angiography (FA) and optical coherence tomography (OCT). Investigations also included an electroretinography (ERG) and histological examination of scleral biopsy. Extraocular malignancies were repeatedly searched. Results: the patient was a 61 year-old Italian man with chronic hepatitis type C. At first visit his best corrected visual acuity (BCVA) was 20/32 in OS and 20/25 in OD. Funduscopy showed multiple patch-shaped pigmented alterations involving macular region and mid retinal periphery. FA showed corresponding areas of late-phase hyperfluorescent pinpoints (figure 1a, OS) and intemediate-phase hypocyanescence (figure 1b, OS), with subtle serous neurosensory retinal detachment confirmed by OCT. Photopic and scotopic ERG tested normal. Systemic prednisone was administered for one month without any improvement. After ten months round pigmentary lesions appeared also in superior scleral surface of both eyes. Biopsy allowed to disclose slightly pigmented spindle cells. BCVA worsened for further 10 months, with enlargement of FA alteration areas but lenses still clear. After 30 months spontaneous coalescence and atrophy of retinal lesions started, paralleled by progressive visual recovery. At the end of our follow up BCVA was 20/25 in OU while scleral pigmentary lesions remained unchanged. Conclusions: we report the case of a patient with main features of BDUMP and some unusual findings. Although not all classical diagnostic criteria were fulfilled, the presence of scleral pigmented lesions and spontaneous visual recovery may enlarge clinical spectrum of the disease.

Novel Homozygous Rax Gene Mutation in Patients With Bilateral Anophthalmia

Purpose: To report the clinical and genetic study of one family and one isolated case of Egyptian origin with clinical anophthalmia. To further determine the role of RAX in anophthalmia and associated cerebral malformations. Methods: Three patients with clinical anophthalmia and first-degree relatives from 2 consanguineous families of Egyptian origin underwent full ophthalmologic, general and neurological examination, and blood drawing. Cerebral MRI was performed in the index case of the family and in the isolated case. Genomic DNA was prepared from venous leukocytes and direct sequencing of all the exons and intron-exon junctions of the RAX gene was performed after PCR amplification Results: Clinical bilateral anophthalmia was observed in all three patients. General and neurological examination was free in the family; obesity and psychomotor developmental delay was noticed in the isolated case. Orbital MRI showed the presence of cystic remnants and reduced optic nerves. Thin optic chiasm was the only observed cerebral malformation on MRI in the index case while the isolated case harboured diffuse cerebral atrophy and absence of the pituitary gland in addition. The three patients carried a novel homozygous mutation (IVS2-3G>A) in the RAX gene, while their parents were heterozygous healthy carriers. Conclusions: To our knowledge, only two isolated cases of anophthalmia have been found to be caused by compound heterozygote RAX mutations, three null and one missense, affecting nuclear localization or DNA-binding homeodomain. We identified a novel homozygous RAX mutation in three patients with bilateral anophthalmia from Northern Egypt. The mutation potentially affects splicing of the last exon and, if not submitted to non-stop decay, could result in a protein that has an aberrant homeodomain and no paired-tail domain. Functional consequences of this change still need to be characterized. This is the first report of homozygous RAX mutation associated with autosomal recessive bilateral anophthalmia

Heidelberg Retina Tomograph in Glaucoma Case-finding

Purpose: To compare the disease classification using optic nerve head imaging against clinical examination combined with perimetry in the case-finding environment.Methods: During a glaucoma screening event at the University Hospital in Lausanne 148 attendees opted to undergo an extended screening exam consisting of perimetry with Octopus (Haag-Streit, Koeniz, Switzerland), tonometry, gonioscopy, slit-lamp optic nerve head examination and Heidelberg Retinal Tomorgraph (HRT, Heidelberg engineering). Classification criteria of an abnormal clinical exam consisted of a cup to disc ratio > 0.6, other disc abnormality (e.g. notching), closed angles, Van Herrick < ¼ and intraocular pressure >21mmHg. In perimetry a square root loss variance (sLV) >3.0 dB was considered abnormal. Those cases with both an abnormal clinical exam and abnormal perimetric results were considered to be glaucoma suspects. An abnormal HRT exam was a global Moorfields Regression Analysis (MRA) result of "outside normal limits". The results from the worse eye for each instrument are reported.Results: The mean age of the patients was 59.9 years (SD ±14.8years). 46 subjects failed the clinical exam. 55 subjects had sLV>3.0dB. 86 subjects failed one or more of the testing components, 21 subjects failed both the clinical exam and perimetry. Two cases of advanced glaucoma were diagnosed on the day of the event. 20 subjects were referred due to other ocular pathology (10 cataract; 2 AMD; 8 other). 16 subjects were outside normal limits with the HRT, of which 11 failed the clinical exam, 9 failed the perimetric exam and 7 failed all three. HRT had a sensitivity of 33% CI [15%,57%] with a specificity of 93% CI [87%,97%].Conclusions: HRT shows good specificity, however the low sensitivity makes it of limited use in the proposed case finding scenario.

Autosomal Recessive Posterior Microphthalmos/Nanophthalmos is Caused by Loss-of-function Mutations in LOC646960, a Novel Gene Encoding a Trypsin-like Serine Protease

Purpose: Posterior microphthalmos (MCOP)/nanophthalmos (NNO) is a developmental anomaly characterized by extreme hyperopia due to short axial length. The population of the Faroe Islands shows a high prevalence of an autosomal recessive form (arMCOP). The gene mutated in arMCOP is not yet known.Methods: Genetic mapping by linkage analysis using microsatellite and single nucleotide polymorphisms, mutation analysis by PCR and sequencing, molecular modellingResults: Having refined the position of the disease locus (MCOP6) in an interval of 250 kb in chromosome 2q37.1 in Faroese families, we detected 3 mutations in a novel gene, LOC646960: Patients of 10 different Faroese families were either homozygous (n=22) for c.926G>C (p.Trp309Ser) or compound heterozygous (n=6) for c.926G>C and c.526C>G (p.Arg176Gly), whereas a homozygous 1 bp duplication (c.1066dupC) was identified in patients with arNNO from a Tunisian family. In two unrelated patients with MCOP, no LOC646960 mutation was found. LOC646960 is expressed in the human adult retina and RPE. The expression of the mouse homologue in the eye can be first detected at E17 and is highest in adults. The predicted protein is a 603 amino acid long secreted trypsin-like serine peptidase. c.1066dupC should result in a functional null allele. Molecular modelling of the p.Trp309Ser mutant suggests that both affinity and reactivity of the enzyme towards in vivo substrates are substantially reduced.Conclusions: Postnatal growth of the eye is important for proper development of the refractive components (emmetropization), and is mainly due to elongation of the posterior segment from 10-11 mm at birth to 15-16 mm at the age of 13 years. Optical defocus leads to changes in axial length by moving the retina towards the image plane. arMCOP may theoretically be explained, in line with the expression pattern of LOC646960, by a postnatal growth retardation of the posterior segment.

Baerveldt aqueous shunt implantation into the ciliary sulcus

Purpose: Aqueous shunt implantation into the anterior chamber is associated with corneal decompensation in up to a third of eyes. Intracameral tube position may affect corneal endothelial cell loss. The authors set out to examine the efficacy and safety of Baerveldt shunt implantation into the ciliary sulcus combined with surgical peripheral iridectomy (SPI). Methods: One hundred eyes prospectively underwent Baerveldt shunt implantation into the cilliary sulcus combined with SPI, leaving a short intracameral tube length (1-2mm). Pre and post operative measures recorded included patient demographics, visual acuity, IOP, number of glaucoma medications (GMs) and all complications. Pre-existing corneal decompensation was recorded. Success was defined as IOP≤21mmHg and 20% reduction in IOP from baseline with or without GMs. Results: Mean age was 65.4 years (±20.4years). Mean follow-up was 10.8 months. Preoperatively IOP was 25.7mmHg (± 9.9mmHg), GMs were 2.9 (±1.2) and VA was 0.4 (±0.3). At one year postoperatively there was a significant drop in IOP (mean= 13.3mmHg (± 5.0mmHg); p<0.001) and number of GMs (mean= 1.3 (±1.4); p<0.001); and no significant change in VA (mean= 0.4 (±0.3); p=0.93). The success rate at one year was 83%. Complications were minor and non sight threatening (10%), there were no cases of postoperative corneal decompensation, tube blockage or iris/corneal-tube contact. Conclusions: The results demonstrate that placement of Baerveldt shunts into the ciliary sulcus with SPI is a safe and efficacious method of IOP reduction in comparison with standard shunt positioning in the anterior chamber. The intracameral tube position combined with SPI avoided tube-iris contact and corneal decompensation. Sulcus placement of aqueous shunts should be considered in pseudophakic eyes.

Evaluation Of "Safe" Trabeculectomy Versus "Safe" Phacotrabeculectomy

Purpose: To evaluate the safety and efficacy of "safe" trabeculectomy (ST) versus "safe" phacotrabeculectomy (SPT).Methods: This study included 72 eyes with medically uncontrolled chronic glaucoma who underwent fornix based trabeculectomy with adjustable/releasable sutures and intraoperative mitomycin C ± phacoemulsification. 36 eyes underwent SPT and 36 eyes had ST. There was no difference between groups for age, intraocular pressure (IOP), diagnosis and gender. Subconjunctival antimetabolite injections and bleb needlings were administered according to bleb vascularity and IOP trends. Main outcome measures were: success rate (definition: IOP≤21mmHg and 20% IOP reduction); number of antimetabolite injections; bleb needlings; glaucoma medications and complications.Results: Mean age (SPT vs ST) was 72.7±12.1 years vs 72.3±12.9 years; p=0.44. Mean preoperative IOP was 24.5±8.8 mmHg vs 24.3±8.2 mmHg; p=0.46. Postoperative IOP was 13.1±4.5mmHg vs 12.4±3.2; p=0.24. Ninety percent of both groups required at least one suture removal. There was no statistically significant difference in success rate between groups, 80% vs 83%; number of eyes requiring antimetabolite injections was 22 eyes (mean 3.2 per eye) vs 23 eyes (mean 2.6 per eye, p=0.24); bleb needlings was performed in 16 eyes (mean 2.5 per eye) vs in 11 eyes (mean 2.0 per eye, p=0.15). The number of eyes restarting glaucoma medications was 5 vs 4. Minor complications were infrequent in both groups, 9 vs 10 eyes.Conclusions: The success and complications rates were similar between groups. The number of postoperative interventions required was slightly greater in the SPT group (not statistically significant). SPT is a safe procedure for patients with coexistent glaucoma and cataract and produces similar IOP-lowering to safe trabeculectomy.

Morgagnian cataract simulating iris neoplasia : case report

Purpose: to describe a case in which the diagnosis of Morganian cataract required clinical and instrumental differentiation from iris pathologies, including iris melanoma. Methods: a 60-years-old Caucasian man referred to our institute for worsening of vision in last few months. Clinical evaluation consisted in complete ophthalmological assessment, ultrasound examination (biomicroscopy and 20MHz), and Magnetic Resonance Imaging (MRI) completed with Susceptibility Weighted Imaging (SWI). Results: traumatic corneal wound of the left eye (LE) had occurred 5 years before, and was treated with medical therapy alone. Best-corrected visual acuity (BCVA) was 3/10 in the right eye (RE) and finger count in the LE, with intraocular pressure at 13 and 20mmHg, respectively. Chronic central serous chorioretinopathy, accounted for the low visual acuity of the RE. Slit-lamp biomicroscopy of the LE was as in Figure 1; LE fundus was not clinically observable. Despite MRI was compatible with an iris solid formation, characterized by contrast enhancement and hyperintense signal in SWI, ultrasound indicated rather a mixed solid and liquid content (moderately echogenic external layer, hyporeflective internal content). Iris root and ciliary body were not significantly altered; the lens showed inhomogeneous content. We considered Morgagnian cataract the most probable diagnosis. Surgery confirmed the presence of a hypermature cataract with prior anterior capsule fissuring; the liquefied cortex infiltrated the iris without anterior chamber seeping. Post-operative BCVA was 3/10 and fundus examination disclosed an advanced macular chronic central serous chorioretinopathy. Conclusions: In the reported case a previous perforating trauma have probably damaged the lens capsule and started cataract progression. Curiously cataract developed percolating into the iris stroma, thus simulating an iris mass. At our knowledge, Morgagnian cataract has never been included in the differential diagnosis of iris mass.

A phase 2 randomized trial of radiotherapy (RT) plus panitumumab compared to chemoradiotherapy in patients with unresected, locally advanced squamous cell carcinoma of the head and neck (SCCHN): interim pooled safety analysis

Background: Panitumumab (pmab), a fully human monoclonal antibody against the epidermal growth factor receptor (EGFR), is indicated as monotherapy for treatment of metastatic colorectal cancer. This ongoing study is designed to assess the efficacy and safety of pmab in combination with radiotherapy (PRT) compared to chemoradiotherapy (CRT) as initial treatment of unresected, locally advanced SCCHN (ClinicalTrials.gov Identifier: NCT00547157). Methods: This is a phase 2, open-label, randomized, multicenter study. Eligible patients (pts) were randomized 2:3 to receive cisplatin 100 mg/m2 on days 1 and 22 of RT or pmab 9.0 mg/kg on days 1, 22, and 43. Accelerated RT (70 to 72 Gy − delivered over 6 to 6.5 weeks) was planned for all pts and was delivered either by intensity-modulated radiation therapy (IMRT) modality or by three-dimensional conformal (3D-CRT) modality. The primary endpoint is local-regional control (LRC) rate at 2 years. Key secondary endpoints include PFS, OS, and safety. An external, independent data monitoring committee conducts planned safety and efficacy reviews during the course of the trial. Results: Pooled data from this planned interim safety analysis includes the first 52 of the 150 planned pts; 44 (84.6%) are male; median (range) age is 57 (33−77) years; ECOG PS 0: 65%, PS 1: 35%; 20 (39%) pts received IMRT, and 32 (61%) pts received 3D-CRT. Fifty (96%) pts completed RT, and 50 pts received RT per protocol without a major deviation. The median (range) total RT dose administered was 72 (64−74) Gy. The most common grade _ 3 adverse events graded using the CTCAE version 3.0 are shown (Table). Conclusions: After the interim safety analysis, CONCERT-2 continues per protocol. Study enrollment is estimated to be completed by October 2009.

FAM161A, associated with autosomal recessive retinitis pigmentosa,localizes at the level of the photoreceptor cilium and interacts with proteins involved in ciliopathies

Purpose: We have previously demonstrated that mutations in the FAM161A gene, encoding a protein with unknown function and no similarities with other characterized sequences, cause autosomal recessive retinitis pigmentosa (RP). The purpose of this work is to investigate the functional role of FAM161A within the retina and its relationship with other proteins involved in RP. Methods: The subcellular localization of FAM161A in the retina was assessed by immunohistochemistry of retinal sections and dissociated photoreceptors from mice, which were stained using antibodies against FAM161A and antibodies against cilium markers. The function of FAM161A was further assessed in ciliated mammalian cell lines by expression of recombinant FAM161A with various fusion tags. The binary interaction between FAM161A and a collection of ciliary and ciliopathy-associated proteins was analyzed using a yeast two-hybrid assay. The results obtained with this technique were validated using independent protein-protein interaction assays (GST-pull downs, co-transfection and co-immunoprecipitation). Results: Native FAM161A localized at the connecting cilium of photoreceptor cells, as demonstrated by immunofluorescence in both dissociated photoreceptors and retinal sections of mice. More specifically, co-staining with markers for ciliary sub-structures (RPGRIP1L, Centrin, RP1, GT335) demonstrated that FAM161A decorated the basal body and the very apical part of the connecting cilium. Upon overexpression in ciliated cultured mammalian cells, FAM161A localized to the ciliary basal body. Yeast two-hybrid analysis of the binary interaction of FAM161A and an array of ciliary proteins revealed the direct interaction of FAM161A with three proteins of which the cognate genes are mutated in retinal ciliopathies. The confirmation of these interactions using different biochemical assays is currently in progress. Conclusions: FAM161A is a ciliary basal body protein of the photoreceptor connecting cilium, rendering the associated RP as a novel retinal ciliopathy. The confined expression of FAM161A in the retina and the direct interaction of FAM161A with other retinal ciliopathy-associated proteins may explain the retinal phenotype of this specific subset of mechanistically and phenotypically connected retinal disorders.

Mir211 Is Dysregulated In Conjunctival Melanocytic proliferations

Purpose Downregulation of TRPM1 mRNA, a transient receptor potential cation channel, has been identified in highly metastatic cutaneous melanoma cell lines. TRPM1 mRNA expression is inversely correlated with skin melanoma metastases. Recent evidence has demonstrated that the tumor suppressive activity of TRPM1 is due to miR211 situated in intron 6 of TRPM1. As we have previously identified a downregulation of TRPM1 mRNA expression in conjunctival melanoma, we decided to assess miR211 expression and its potential target gene IGF2R and KCNMA1 in conjunctival melanocytic proliferations. As MITF has been shown to regulate both TRPM1 and mir211 expression, we also assessed MITF expression in our series. Methods Expression of miR211 was assessed by in situ hybridization in 14 conjunctival naevi and 14 conjunctival melanoma. Integrity of miRNA in tissues was evaluated in each sample with the preservation of miR126 expression in endothelial cells. Protein expression of MITF, IGF2R and KCNMA1 was assessed by immunohistochemistry. Statistical analysis was performed with JUMP 8,0 software. In situ hybridization and immunohistochemistry were assessed independently by two observers. Results There were 7 subepithelial nevi and 7 compound nevi. There were 5 female and 9 male. The population mean age was 48.7 ± 6.4 years (SEM). miR211 was found in 11 nevi (79%). MITF was expressed in all the nevi. IGF2R was found in 13 nevi. KCNMA1 was found in 57% of the nevi.The melanoma group was composed of 9 females and 5 males with a mean age of 67 ± 4.8 years (SEM). Using the recent TNM classification, 5 tumors were belonging to the T1, 3 to theT2 and 6 to the T3 categories. miR211 was found in 5 melanoma (36%). There was a significant downregulation of miR211 in the melanoma compared to the nevi (p=0,0219). MITF was found in 13 melanoma (93%). IGF2R and KCNMA1 were respectively found in 71% and 77% of the melanoma. There was no significant differential expression of MITF, KCNMA1 and IGF2R between the nevi and the melanoma as well as no association between miR211 expression and protein expression of two potential target genes Conclusions In vivo miR211 is significantly reduced in conjunctival melanoma compared to conjunctival nevi. No correlation between mir211 expression and two potential target genes KCNMA1 and IGF2R was observed.

The metal ion binding protein Cnnm4 is mutated in rod-cone dystrophy/amelogenesis imperfecta syndrome

Purpose:To identify the gene causing rod-cone dystrophy/amelogenesis imperfecta Methods:Homozygosity mapping was performed using the Affymetrix 50K XbaI array in one family and candidate genes in the linked interval were sequenced with ABI Dye Terminator, vers. 1 in the index patient of 3 families. The identified mutations were screened in normal control individuals. Expression analyses were performed on RNA extracted from the brain, various parts of the eye and teeth; immunostaining was done on mouse eyes and jaw and knock-down experiments were carried out in zebrafish embroys. Results:Sequencing the coding regions of ancient conserved domain protein 4 (CNNM4), a metal ions transporter, revealed a 1-base pair duplication (p.L438fs) in family A, a p.R236Q mutation in family B and a p.L324P in family C. All these mutations were homozygous and involved very conserved amino acids in paralogs and orthologs. Immunostaining and RT-PCR confirmed that CNNM4 was strongly expressed in various parts of the eye and in the teeth. Morpholino experiments in zebrafish showed a loss of ganglion cells at 5 days post fertilization. Conclusions:The rod-cone dystrophy/amelogenesis imperfecta syndrome is caused by mutation in CNNM4 and is due to aberrant metal ion homeostasis.