Sample records for amaurosis fugax

  1. Reversible monocular cataract simulating amaurosis fugax. (United States)

    Paylor, R R; Selhorst, J B; Weinberg, R S


    In a patient having brittle, juvenile-onset diabetes, transient monocular visual loss occurred repeatedly whenever there were wide fluctuations in serum glucose. Amaurosis fugax was suspected. The visual loss differed, however, in that it persisted over a period of hours to several days. Direct observation eventually revealed that the relatively sudden change in vision of one eye was associated with opacification of the lens and was not accompanied by an afferent pupillary defect. Presumably, a hyperosmotic gradient had developed with the accumulation of glucose and sorbitol within the lens. Water was drawn inward, altering the composition of the lens fibers and thereby lowering the refractive index, forming a reversible cataract. Hypoglycemia is also hypothesized to have played a role in the formation of a higher osmotic gradient. The unilaterality of the cataract is attributed to variation in the permeability of asymmetric posterior subcapsular cataracts.

  2. A fatal case of primary cardiac chondrosarcoma presenting with amaurosis fugax

    DEFF Research Database (Denmark)

    Sundbøll, Jens; Hansson, Nils Henrik Stubkjær; Baerentzen, Steen


    A 64-year-old previously healthy woman consulted her general practitioner because of recurrent episodes of right-sided monocular transient visual loss (ie, amaurosis fugax). At first, these symptoms were followed over time, but as the attacks worsened, and were accompanied by dizziness and general...

  3. Detection of unstable carotid plaque by tissue Doppler imaging and contrast-enhanced ultrasound in a patient with recurrent amaurosis fugax. (United States)

    Kunte, Hagen; Rückert, Ralph-Ingo; Schmidt, Charlotte; Harms, Lutz; Kasper, Antje-Susanne; Hellweg, Rainer; Grigoryev, Maria; Fischer, Thomas; Kronenberg, Golo


    Ultrasound (US) is one of the most important diagnostic tools available for the detection and evaluation of carotid stenosis. The case of a 70-year-old woman with recurrent right-sided amaurosis fugax presented here highlights the way in which tissue Doppler imaging (TDI) and contrast-enhanced US (CEUS) may aid in the diagnosis of carotid plaque vulnerability. Furthermore, the novel inverse fly-through technique was used for the three-dimensional visualization of the carotid stenosis.

  4. Detection of Unstable Carotid Plaque by Tissue Doppler Imaging and Contrast-Enhanced Ultrasound in a Patient with Recurrent Amaurosis Fugax

    Directory of Open Access Journals (Sweden)

    Hagen Kunte


    Full Text Available Ultrasound (US is one of the most important diagnostic tools available for the detection and evaluation of carotid stenosis. The case of a 70-year-old woman with recurrent right-sided amaurosis fugax presented here highlights the way in which tissue Doppler imaging (TDI and contrast-enhanced US (CEUS may aid in the diagnosis of carotid plaque vulnerability. Furthermore, the novel inverse fly-through technique was used for the three-dimensional visualization of the carotid stenosis.

  5. Linear interictal pain in Epicrania Fugax. (United States)

    Pareja, Juan A; Bandrés, Pablo


    Epicrania Fugax is a paroxysmal, short-lasting, head pain moving across one hemicranium, describing a linear or zag trajectory, starting and ending in territories of different nerves. Between attacks, patients are usually free of symptoms. We describe an Epicrania Fugax patient complaining of interictal pain. The interictal pain was line-shaped and extended across the usual starting and ending points of the typical Epicrania Fugax paroxysms. Although rarely encountered, persistent linear pain may be a feature of Epicrania Fugax.

  6. Bilateral amaurosis caused by Salmonella enteritidis infection. (United States)

    Cerovski, Branimir; Barisić, Nina; Vidović, Tomislav; Petricek, Igor; Cerovski, Jasenka


    The aim of this paper was to show the potential of Salmonella enteritidis infection to eventually result in visual impairment. A case of salmonellosis in a 6-year-old boy, caused by intake of a cake made from eggs infected with Salmonella enteritidis, is presented. Prolonged duration of the disease was followed by complete remission of neurologic complications and persistent amaurosis with bilateral optic nerve atrophy. A severe form of Salmonella enterocolitis with neurologic involvement can lead to optic nerve lesion with consequential loss of vision.

  7. Female sex pheromones of two Japanese saturniid species, Rhodinia fugax and Loepa sakaei: identification, synthesis, and field evaluation. (United States)

    Yan, Qi; Kanegae, Akiko; Miyachi, Takashi; Naka, Hideshi; Tatsuta, Haruki; Ando, Tetsu


    While 11 species in the family Saturniidae are found in Japan, no sex pheromones of the native species had been investigated previously. We collected larvae of Rhodinia fugax in Nagano and Tottori Prefecture, and of Loepa sakaei in Okinawa Prefecture, and extracted sex pheromones of these two species from virgin female moths. In gas chromatography-electroantennogram detection (GC-EAD) analyses, male antennae of each species responded to one component in the respective pheromone extracts of conspecific females. Chemical analyses of the extracts by GC/mass spectrometry revealed that the EAD-active compounds of R. fugax and L. sakaei were a hexadecadienal and a tetradecadienyl acetate, respectively. The two species belong to the subfamily Saturniinae, and the mass spectra of both were similar to that of the 6,11-hexadecadienyl acetate identified from Antheraea polyphemus, classified in the same subfamily, suggesting the same 6,11-dienyl structure for the C16 aldehyde and a 4,9-dienyl structure for the C14 acetate. Based on this assumption, four geometrical isomers of each dienyl compound were stereoselectively synthesized via acetylene intermediates, compared to the natural products, and tested in the field. Male catches confirmed the pheromone structures of the two Japanese saturniid species as (6E,11Z)-6,11-hexadecadienal for R. fugax and (4E,9Z)-4,9-tetradecadienyl acetate for L. sakaei. The compounds have a characteristic 1,6-dienyl motif common to the pheromones of Saturniinae species.

  8. Ritual relieved axial dystonia triggered by gaze-evoked amaurosis. (United States)

    Jacome, D E


    A woman with chronic posttraumatic axial lateropulsion cervical dystonia ("belly dancer's head") found relief of her spontaneous dystonic spasms by the sequential performance of an elaborate motor ritual. During an episode of left optic papillitis caused by central retinal vein occlusion, gaze-evoked amaurosis of the left eye developed, preceded by achromatopsia, during left lateral gaze. Gaze-evoked amaurosis triggered axial dystonia, which was followed by her unique, stereotyped, dystonia-relieving ritual that simulated a slow dance. Visual symptoms improved progressively in 1 year. Eventually, she was unable to trigger her dystonia by eye movements. Spontaneous dystonia remained otherwise unchanged from before the episode of papillitis and was still relieved by her unique ritual.

  9. Mutations in LCA5, encoding the ciliary protein lebercilin, cause Leber congenital amaurosis.

    NARCIS (Netherlands)

    Hollander, A.I. den; Koenekoop, R.K.; Mohamed, M.D.; Arts, H.H.; Boldt, K.; Towns, K.V.; Sedmak, T.; Beer, M. de; Nagel-Wolfrum, K.; McKibbin, M.; Dharmaraj, S.; Lopez, I.; Ivings, L.; Williams, G.A.; Springell, K.; Woods, C.G.; Jafri, H.; Rashid, Y.; Strom, T.M.; Zwaag, B. van der; Gosens, I.; Kersten, F.F.J.; Wijk, E. van; Veltman, J.A.; Zonneveld, M.N.; Beersum, S.E.C. van; Maumenee, I.H.; Wolfrum, U.; Cheetham, M.E.; Ueffing, M.; Cremers, F.P.M.; Inglehearn, C.F.; Roepman, R.


    Leber congenital amaurosis (LCA) causes blindness or severe visual impairment at or within a few months of birth. Here we show, using homozygosity mapping, that the LCA5 gene on chromosome 6q14, which encodes the previously unknown ciliary protein lebercilin, is associated with this disease. We dete

  10. Mutations in LCA5 are an uncommon cause of Leber congenital amaurosis (LCA) type II. (United States)

    Gerber, Sylvie; Hanein, Sylvain; Perrault, Isabelle; Delphin, Nathalie; Aboussair, Nisrine; Leowski, Corinne; Dufier, Jean-Louis; Roche, Olivier; Munnich, Arnold; Kaplan, Josseline; Rozet, Jean-Michel


    Leber congenital amaurosis (LCA) is the earliest and most severe form of inherited retinal dystrophy responsible for blindness or severe visual impairment at birth or within the first months of life. Up to date, ten LCA genes have been identified. Three of them account for ca. 43% of families and are responsible for a congenital severe stationary cone-rod dystrophy (Type I, 60% of LCA) while the seven remaining genes account for 32% of patients and are responsible for a progressive yet severe rod-cone dystrophy (Type II, 40% of LCA ). Recently, mutations in LCA5, encoding the ciliary protein lebercilin, were reported to be a rare cause of leber congenital amaurosis. The purpose of this study was to evaluate the involvement of this novel gene and to look for genotype-phenotype correlations. Here we report the identification of three novel LCA5 mutations (3/3 homozygous) in three families confirming the modest implication of this gene in our series (3/179; 1.7%). Besides, we suggest that the phenotype of these patients affected with a particularly severe form of LCA type II may represent a continuum with LCA type I.

  11. Ocular and extra-ocular features of patients with Leber congenital amaurosis and mutations in CEP290

    NARCIS (Netherlands)

    Yzer, Suzanne; den Hollander, Anneke I.; Lopez, Irma; Pott, Jan-Willem R.; de Faber, Jan Tjeerd H. N.; Cremers, Frans P. M.; Koenekoop, Robert K.; van den Born, L. Ingeborgh


    Purpose: This study investigated the centrosomal protein, 290-KD (CEP290) associated genotype and ocular and extra-ocular phenotype in 18 patients with Leber congenital amaurosis (LCA). Methods: Eighteen patients with LCA from 14 families with mutations in the CEP290 gene were identified with sequen

  12. Ocular and extra-ocular features of patients with Leber congenital amaurosis and mutations in CEP290

    NARCIS (Netherlands)

    Yzer, S.; Hollander, A.I. den; Lopez, I.; Pott, J.W.; Faber, J.T. de; Cremers, F.P.; Koenekoop, R.K.; Born, L.I. van den


    PURPOSE: This study investigated the centrosomal protein, 290-KD (CEP290) associated genotype and ocular and extra-ocular phenotype in 18 patients with Leber congenital amaurosis (LCA). METHODS: Eighteen patients with LCA from 14 families with mutations in the CEP290 gene were identified with sequen

  13. 棒头草对16种夏熟作物田常用除草剂的敏感性%Sensitivity of Polypogon fugax to 16 Herbicides Frequently Used in Summer-Harvest Crops

    Institute of Scientific and Technical Information of China (English)

    鄢志会; 曾婷婷; 吴宪; 李俊; 陈国奇; 董立尧


    Polypogon fugax is a common weed in summer-harvest crop fields in China,even being the principal weed in some areas.A series of whole-plant bioassays were conducted to test the response of P.fugax to five pre-emergence and 11 post-emergence herbicides frequently used in summer-harvest crops.The EC90 doses ( caused 90% inhibition of the fresh weight) of the five pre-emergence herbicides ( active ingredient) to P.fugax were 6.58 g acetochlor/hm2 , 1 900 g trifluralin/hm2 ,120 g diflufenican/hm2 ,1 560 g isoproturon/hm2 and 3 373 g chlorotoluron/hm2 .The EC90 dose of acetochlor to P.fugax was much lower than its recommended low dose and that of diflufenican was lower than its recommended high dose, while those of trifluralin, chlorotoluron and isoproturon were higher than the recommended high doses,especially for trifluralin and chlorotoluron.The EC90 doses of 11 pre-emergence herbicides to P.fugax were clethodim 11 . 9 g/hm2 , mesosulfuron - methyl 4.16 g/hm2 , pyroxsulam 12.6 g/hm2 , pinoxaden 21.5 g/hm2 , haloxyfop -P -methyl 81.8 g/hm2 , fenoxaprop-P-ethyl 20.15 g/hm 2,quizalofop-P-ethyl 6.77 g/hm 2,fluazifop-P-butyl 32.6 g/hm 2,flucarbazone-sodium 176 g /hm2 , clodinafop -propargyl 20.15 g/hm2 , and sethoxydim 90.0 g/hm2 .Among the 11 post-emergence herbicides,only flucarbazone-sodium and haloxyfop-P-methyl had EC90 doses higher than the rec-ommended high dose.Therefore,acetochlor and diflufenican as pre-emergence herbicides and the 11 post-emergence herbicides except for flucarbazone-sodium and haloxyfop-P-methyl could be used to control P.fugax effectively, while paying special attention to the selectivity of the different herbicides to the crop .%棒头草( Polypogon fugax)是我国夏熟作物田常见杂草,在一些地区已成为主要杂草。采用整株生物测定法研究了棒头草对夏熟作物田常用的5种土壤处理和11种茎叶处理除草剂的敏感性。结果表明,5种土壤处理剂对棒头草抑制地上部分生长90

  14. CCT2 Mutations Evoke Leber Congenital Amaurosis due to Chaperone Complex Instability (United States)

    Minegishi, Yuriko; Sheng, XunLun; Yoshitake, Kazutoshi; Sergeev, Yuri; Iejima, Daisuke; Shibagaki, Yoshio; Monma, Norikazu; Ikeo, Kazuho; Furuno, Masaaki; Zhuang, Wenjun; Liu, Yani; Rong, Weining; Hattori, Seisuke; Iwata, Takeshi


    Leber congenital amaurosis (LCA) is a hereditary early-onset retinal dystrophy that is accompanied by severe macular degeneration. In this study, novel compound heterozygous mutations were identified as LCA-causative in chaperonin-containing TCP-1, subunit 2 (CCT2), a gene that encodes the molecular chaperone protein, CCTβ. The zebrafish mutants of CCTβ are known to exhibit the eye phenotype while its mutation and association with human disease have been unknown. The CCT proteins (CCT α-θ) forms ring complex for its chaperon function. The LCA mutants of CCTβ, T400P and R516H, are biochemically instable and the affinity for the adjacent subunit, CCTγ, was affected distinctly in both mutants. The patient-derived induced pluripotent stem cells (iPSCs), carrying these CCTβ mutants, were less proliferative than the control iPSCs. Decreased proliferation under Cct2 knockdown in 661W cells was significantly rescued by wild-type CCTβ expression. However, the expression of T400P and R516H didn’t exhibit the significant effect. In mouse retina, both CCTβ and CCTγ are expressed in the retinal ganglion cells and connecting cilium of photoreceptor cells. The Cct2 knockdown decreased its major client protein, transducing β1 (Gβ1). Here we report the novel LCA mutations in CCTβ and the impact of chaperon disability by these mutations in cellular biology. PMID:27645772

  15. Plasticity of the human visual system after retinal gene therapy in patients with Leber's congenital amaurosis. (United States)

    Ashtari, Manzar; Zhang, Hui; Cook, Philip A; Cyckowski, Laura L; Shindler, Kenneth S; Marshall, Kathleen A; Aravand, Puya; Vossough, Arastoo; Gee, James C; Maguire, Albert M; Baker, Chris I; Bennett, Jean


    Much of our knowledge of the mechanisms underlying plasticity in the visual cortex in response to visual impairment, vision restoration, and environmental interactions comes from animal studies. We evaluated human brain plasticity in a group of patients with Leber's congenital amaurosis (LCA), who regained vision through gene therapy. Using non-invasive multimodal neuroimaging methods, we demonstrated that reversing blindness with gene therapy promoted long-term structural plasticity in the visual pathways emanating from the treated retina of LCA patients. The data revealed improvements and normalization along the visual fibers corresponding to the site of retinal injection of the gene therapy vector carrying the therapeutic gene in the treated eye compared to the visual pathway for the untreated eye of LCA patients. After gene therapy, the primary visual pathways (for example, geniculostriate fibers) in the treated retina were similar to those of sighted control subjects, whereas the primary visual pathways of the untreated retina continued to deteriorate. Our results suggest that visual experience, enhanced by gene therapy, may be responsible for the reorganization and maturation of synaptic connectivity in the visual pathways of the treated eye in LCA patients. The interactions between the eye and the brain enabled improved and sustained long-term visual function in patients with LCA after gene therapy.

  16. Homozygosity Mapping in Leber Congenital Amaurosis and Autosomal Recessive Retinitis Pigmentosa in South Indian Families.

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    Sundaramurthy Srilekha

    Full Text Available Leber congenital amaurosis (LCA and retinitis pigmentosa (RP are retinal degenerative diseases which cause severe retinal dystrophy affecting the photoreceptors. LCA is predominantly inherited as an autosomal recessive trait and contributes to 5% of all retinal dystrophies; whereas RP is inherited by all the Mendelian pattern of inheritance and both are leading causes of visual impairment in children and young adults. Homozygosity mapping is an efficient strategy for mapping both known and novel disease loci in recessive conditions, especially in a consanguineous mating, exploiting the fact that the regions adjacent to the disease locus will also be homozygous by descent in such inbred children. Here we have studied eleven consanguineous LCA and one autosomal recessive RP (arRP south Indian families to know the prevalence of mutations in known genes and also to know the involvement of novel loci, if any. Complete ophthalmic examination was done for all the affected individuals including electroretinogram, fundus photograph, fundus autofluorescence, and optical coherence tomography. Homozygosity mapping using Affymetrix 250K HMA GeneChip on eleven LCA families followed by screening of candidate gene(s in the homozygous block identified mutations in ten families; AIPL1 - 3 families, RPE65- 2 families, GUCY2D, CRB1, RDH12, IQCB1 and SPATA7 in one family each, respectively. Six of the ten (60% mutations identified are novel. Homozygosity mapping using Affymetrix 10K HMA GeneChip on the arRP family identified a novel nonsense mutation in MERTK. The mutations segregated within the family and was absent in 200 control chromosomes screened. In one of the eleven LCA families, the causative gene/mutation was not identified but many homozygous blocks were noted indicating that a possible novel locus/gene might be involved. The genotype and phenotype features, especially the fundus changes for AIPL1, RPE65, CRB1, RDH12 genes were as reported earlier.

  17. Comprehensive genotyping reveals RPE65 as the most frequently mutated gene in Leber congenital amaurosis in Denmark

    DEFF Research Database (Denmark)

    Astuti, Galuh D N; Bertelsen, Mette; Preising, Markus N;


    Leber congenital amaurosis (LCA) represents the most severe form of inherited retinal dystrophies with an onset during the first year of life. Currently, 21 genes are known to be associated with LCA and recurrent mutations have been observed in AIPL1, CEP290, CRB1 and GUCY2D. In addition, sequenc...... therapies.European Journal of Human Genetics advance online publication, 2 December 2015; doi:10.1038/ejhg.2015.241.......Leber congenital amaurosis (LCA) represents the most severe form of inherited retinal dystrophies with an onset during the first year of life. Currently, 21 genes are known to be associated with LCA and recurrent mutations have been observed in AIPL1, CEP290, CRB1 and GUCY2D. In addition, sequence...... analysis of LRAT and RPE65 may be important in view of treatments that are emerging for patients carrying variants in these genes. Screening of the aforementioned variants and genes was performed in 64 Danish LCA probands. Upon the identification of heterozygous variants, Sanger sequencing was performed...

  18. Bax-induced apoptosis in Leber's congenital amaurosis: a dual role in rod and cone degeneration.

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    Séverine Hamann

    Full Text Available Pathogenesis in the Rpe65(-/- mouse model of Leber's congenital amaurosis (LCA is characterized by a slow and progressive degeneration of the rod photoreceptors. On the opposite, cones degenerate rapidly at early ages. Retinal degeneration in Rpe65(-/- mice, showing a null mutation in the gene encoding the retinal pigment epithelium 65-kDa protein (Rpe65, was previously reported to depend on continuous activation of a residual transduction cascade by unliganded opsin. However, the mechanisms of apoptotic signals triggered by abnormal phototransduction remain elusive. We previously reported that activation of a Bcl-2-dependent pathway was associated with apoptosis of rod photoreceptors in Rpe65(-/- mice during the course of the disease. In this study we first assessed whether activation of Bcl-2-mediated apoptotic pathway was dependent on constitutive activation of the visual cascade through opsin apoprotein. We then challenged the direct role of pro-apoptotic Bax protein in triggering apoptosis of rod and cone photoreceptors.Quantitative PCR analysis showed that increased expression of pro-apoptotic Bax and decreased level of anti-apoptotic Bcl-2 were restored in Rpe65(-/-/Gnat1(-/- mice lacking the Gnat1 gene encoding rod transducin. Moreover, photoreceptor apoptosis was prevented as assessed by TUNEL assay. These data indicate that abnormal activity of opsin apoprotein induces retinal cell apoptosis through the Bcl-2-mediated pathway. Following immunohistological and real-time PCR analyses, we further observed that decreased expression of rod genes in Rpe65-deficient mice was rescued in Rpe65(-/-/Bax(-/- mice. Histological and TUNEL studies confirmed that rod cell demise and apoptosis in diseased Rpe65(-/- mice were dependent on Bax-induced pathway. Surprisingly, early loss of cones was not prevented in Rpe65(-/-/Bax(-/- mice, indicating that pro-apoptotic Bax was not involved in the pathogenesis of cone cell death in Rpe65-deficient mice

  19. Leber先天黑矇的临床研究%Clinical study on Leber congenital amaurosis

    Institute of Scientific and Technical Information of China (English)

    睢瑞芳; 赵潺; 姜茹欣; 周崎; 于伟泓; 董方田


    Objectives To observe the clinical characteristics of Leber congenital amaurosis (LCA)and analyze the features to differentiate LCA from other similar disorders.Methods Prospective study of 15LCA patients which include 10 males and 5 females,aged from 2 to 31 years with the mean age 13.6 years.Medical history,family history,perinatal conditions,as well as complete ocular evaluations were well documented.Among the subjects,12 patients underwent optometry check,10 patients underwent ERG and 8 patients had OCT testing.Results All of the patients had nystagmus and sluggish pupillary reflex.The visual acuity distributed from light perception to 0.1.Fivepatients (33.3%) were presented with photophobia,while 7 patients (46.7%) had nyctalopia.Among 12 cases underwent refraction examination,6 patients (50% ) had spherical equivalent of≥ + 5D;1 patient(8.3 % )had spherical equivalent of≥+5D;2patients (16.7%) had bilateral mild to moderate hyperopia;1 patient (8.3%) had one emmertropic eye and one mild myopic eye;2 patients (16.7%) had moderate to high myopia.Eight patients (53.3%) had enophthalmus,4 patients (26.7%) had oculo-digital sign.All of the 10 patients underwent ERG showed extinguished waveform.Under OCT assesement,7 patients had decreased fovea thickness;1 patient had increased fovea thickness,complicated by epiretinal membrane;mild abnormality of microstrueture of the retina with diminished and disrupted IS/OS hyperreflectivity were found in 2 cases;while more pronounced disarrangement of the retinal layers were found in 6 cases,inner layers were better reserved in all patients.Conclusions Severe visual impairment or blindness,nystagmus,pupillary reflex,extinguished ERG and hyperopia are main clinical characteristics of LCA.%目的 观察中国Leber先天黑嚎(LCA)患者的临床特征.方法 前瞻性临床研究,分析15例LCA患者的临床资料.其中,男性10例,女性5例,年龄2~31岁,平均13.6岁.所有患者就诊时详细记录病史、家族

  20. Insights into the role of RD3 in guanylate cyclase trafficking, photoreceptor degeneration and Leber Congenital Amaurosis

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    Robert S. Molday


    Full Text Available RD3 is an evolutionarily conserved 23 kDa protein expressed in rod and cone photoreceptor cells. Mutations in the gene encoding RD3 resulting in unstable non-functional C-terminal truncated proteins are responsible for early onset photoreceptor degeneration in Leber Congenital Amaurosis 12 (LCA12 patients, the rd3 mice, and the rcd2 collies. Recent studies have shown that RD3 interacts with guanylate cyclases GC1 and GC2 in retinal cell extracts and HEK293 cells co-expressing GC and RD3. This interaction inhibits GC catalytic activity and promotes the exit of GC1 and GC2 from the endoplasmic reticulum and their trafficking to photoreceptor outer segments. Adeno-associated viral vector delivery of the normal RD3 gene to photoreceptors of the Rd3 mouse restores GC1 and GC2 expression and outer segment localization and leads to the long-term recovery of visual function and photoreceptor cell survival. This review focuses on the genetic and biochemical studies that have provided insight into the role of RD3 in photoreceptor function and survival.

  1. Overlap of abnormal photoreceptor development and progressive degeneration in Leber congenital amaurosis caused by NPHP5 mutation. (United States)

    Downs, Louise M; Scott, Erin M; Cideciyan, Artur V; Iwabe, Simone; Dufour, Valerie; Gardiner, Kristin L; Genini, Sem; Marinho, Luis Felipe; Sumaroka, Alexander; Kosyk, Mychajlo S; Swider, Malgorzata; Aguirre, Geoffrey K; Jacobson, Samuel G; Beltran, William A; Aguirre, Gustavo D


    Ciliary defects can result in severe disorders called ciliopathies. Mutations in NPHP5 cause a ciliopathy characterized by severe childhood onset retinal blindness, Leber congenital amaurosis (LCA), and renal disease. Using the canine NPHP5-LCA model we compared human and canine retinal phenotypes, and examined the early stages of photoreceptor development and degeneration, the kinetics of photoreceptor loss, the progression of degeneration and the expression profiles of selected genes. NPHP5-mutant dogs recapitulate the human phenotype of very early loss of rods, and relative retention of the central retinal cone photoreceptors that lack function. In mutant dogs, rod and cone photoreceptors have a sensory cilium, but develop and function abnormally and then rapidly degenerate; L/M cones are more severely affected than S-cones. The lack of outer segments in mutant cones indicates a ciliary dysfunction. Genes expressed in mutant rod or both rod and cone photoreceptors show significant downregulation, while those expressed only in cones are unchanged. Many genes in cell-death and -survival pathways also are downregulated. The canine disease is a non-syndromic LCA-ciliopathy, with normal renal structures and no CNS abnormalities. Our results identify the critical time points in the pathogenesis of the photoreceptor disease, and bring us closer to defining a potential time window for testing novel therapies for translation to patients.

  2. The Leber congenital amaurosis protein AIPL1 and EB proteins co-localize at the photoreceptor cilium.

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    Juan Hidalgo-de-Quintana

    Full Text Available The aim of this study was to investigate the interaction and co-localization of novel interacting proteins with the Leber congenital amaurosis (LCA associated protein aryl hydrocarbon receptor interacting protein-like 1 (AIPL1.The CytoTrapXR yeast two-hybrid system was used to screen a bovine retinal cDNA library. A novel interaction between AIPL1 and members of the family of EB proteins was confirmed by directed yeast two-hybrid analysis and co-immunoprecipitation assays. The localization of AIPL1 and the EB proteins in cultured cells and in retinal cryosections was examined by immunofluorescence microscopy and cryo-immunogold electron microscopy.Yeast two-hybrid (Y2H analysis identified the interaction between AIPL1 and the EB proteins, EB1 and EB3. EB1 and EB3 were specifically co-immunoprecipitated with AIPL1 from SK-N-SH neuroblastoma cells. In directed 1:1 Y2H analysis, the interaction of EB1 with AIPL1 harbouring the LCA-causing mutations A197P, C239R and W278X was severely compromised. Immunofluorescent confocal microscopy revealed that AIPL1 did not co-localize with endogenous EB1 at the tips of microtubules, endogenous EB1 at the microtubule organising centre following disruption of the microtubule network, or with endogenous β-tubulin. Moreover, AIPL1 did not localize to primary cilia in ARPE-19 cells, whereas EB1 co-localized with the centrosomal marker pericentrin at the base of primary cilia. However, both AIPL1 and the EB proteins, EB1 and EB3, co-localized with centrin-3 in the connecting cilium of photoreceptor cells. Cryo-immunogold electron microscopy confirmed the co-localization of AIPL1 and EB1 in the connecting cilia in human retinal photoreceptors.AIPL1 and the EB proteins, EB1 and EB3, localize at the connecting cilia of retinal photoreceptor cells, but do not co-localize in the cellular microtubule network or in primary cilia in non-retinal cells. These findings suggest that AIPL1 function in these cells is not related

  3. Leber Congenital Amaurosis (United States)

    ... Resources Low Vision Specialists Retinal Physicians My Retina Tracker Registry Genetic Testing Clinical Trials Join the Fight ... which measure visual function, detect little if any activity in the retina. A low level of retinal ...

  4. Akut glaukom efter endarterektomi af arteria carotis interna

    DEFF Research Database (Denmark)

    Lindholt, J S; Klaerke, A


    A 71 year-old woman had 85% and 60% stenoses of the right and left internal carotid arteries, respectively. Right-sided endarterectomy was performed because of amaurosis fugax. Two days postoperatively, she developed classical symptoms and signs of acute glaucoma. Right-sided acute angle closure...

  5. Centrosomal-ciliary gene CEP290/NPHP6 mutations result in blindness with unexpected sparing of photoreceptors and visual brain: implications for therapy of Leber congenital amaurosis. (United States)

    Cideciyan, Artur V; Aleman, Tomas S; Jacobson, Samuel G; Khanna, Hemant; Sumaroka, Alexander; Aguirre, Geoffrey K; Schwartz, Sharon B; Windsor, Elizabeth A M; He, Shirley; Chang, Bo; Stone, Edwin M; Swaroop, Anand


    Mutations in the centrosomal-ciliary gene CEP290/NPHP6 are associated with Joubert syndrome and are the most common cause of the childhood recessive blindness known as Leber congenital amaurosis (LCA). An in-frame deletion in Cep290 shows rapid degeneration in the rod-rich mouse retina. To explore the mechanisms of the human retinal disease, we studied CEP290-LCA in patients of different ages (7-48 years) and compared results to Cep290-mutant mice. Unexpectedly, blind CEP290-mutant human retinas retained photoreceptor and inner laminar architecture in the cone-rich central retina, independent of severity of visual loss. Surrounding the cone-rich island was photoreceptor loss and distorted retina, suggesting neural-glial remodeling. The mutant mouse retina at 4-6 weeks of age showed similar features of retinal remodeling, with altered neural and synaptic laminae and Muller glial activation. The visual brain pathways in CEP290-LCA were anatomically intact. Our findings of preserved foveal cones and visual brain anatomy in LCA with CEP290 mutations, despite severe blindness and rapid rod cell death, suggest an opportunity for visual restoration of central vision in this common form of inherited blindness.

  6. Progress in gene therapy study of Leber congenital amaurosis%Leber先天性黑矇的基因治疗研究进展

    Institute of Scientific and Technical Information of China (English)

    潘珊珊; 郑钦象; 李文生; 庞继景


    Leber congenital amaurosis (LCA)is an early onset retinal dystrophy that causes severe visual impairment. With the development of molecular genetics and the therapeutic gene replacement technology, the adeno-associated viral (AAV) vector-mediated gene therapy for LCA achieved encouraging progress in the past decade. The success of the Phase Ⅰ clinical trials of human RPE65 gene therapy for LCA Ⅱ patients makes it a pioneer in the field of retinal gene therapy and brings light to the cure of other hereditary retinopathy. This article briefly reviews the recent developments in the preclinical animal experiments and Phase Ⅰ clinical trials for LCA.%Leber先天性黑矇(LCA)是一种严重的先天性致肓遗传性视网膜疾病.近1O年来,随着分子遗传学的发展及基因治疗技术的进步,以腺相关病毒载体介导的LCA基因治疗研究取得了令人鼓舞的进展,尤其是对LCAⅡ患者进行的RPE65基因治疗的Ⅰ期临床试验的成功使其成为眼科遗传性疾病基因治疗领域中的先行者,为今后进行其他遗传性视网膜疾病的基因治疗开辟了光明的前景.本文就目前LCA基因治疗的临床前研究及Ⅰ期临床试验的进展等方面作一综述.

  7. Leber congenital amaurosis: comprehensive survey of the genetic heterogeneity, refinement of the clinical definition, and genotype-phenotype correlations as a strategy for molecular diagnosis. (United States)

    Hanein, Sylvain; Perrault, Isabelle; Gerber, Sylvie; Tanguy, Gaëlle; Barbet, Fabienne; Ducroq, Dominique; Calvas, Patrick; Dollfus, Hélène; Hamel, Christian; Lopponen, Tuija; Munier, Francis; Santos, Louisa; Shalev, Stavit; Zafeiriou, Dimitrios; Dufier, Jean-Louis; Munnich, Arnold; Rozet, Jean-Michel; Kaplan, Josseline


    Leber congenital amaurosis (LCA) is the earliest and most severe form of all inherited retinal dystrophies, responsible for congenital blindness. Disease-associated mutations have been hitherto reported in seven genes. These genes are all expressed preferentially in the photoreceptor cells or the retinal pigment epithelium but they are involved in strikingly different physiologic pathways resulting in an unforeseeable physiopathologic variety. This wide genetic and physiologic heterogeneity that could largely increase in the coming years, hinders the molecular diagnosis in LCA patients. The genotyping is, however, required to establish genetically defined subgroups of patients ready for therapy. Here, we report a comprehensive mutational analysis of the all known genes in 179 unrelated LCA patients, including 52 familial and 127 sporadic (27/127 consanguineous) cases. Mutations were identified in 47.5% patients. GUCY2D appeared to account for most LCA cases of our series (21.2%), followed by CRB1 (10%), RPE65 (6.1%), RPGRIP1 (4.5%), AIPL1 (3.4%), TULP1 (1.7%), and CRX (0.6%). The clinical history of all patients with mutations was carefully revisited to search for phenotype variations. Sound genotype-phenotype correlations were found that allowed us to divide patients into two main groups. The first one includes patients whose symptoms fit the traditional definition of LCA, i.e., congenital or very early cone-rod dystrophy, while the second group gathers patients affected with severe yet progressive rod-cone dystrophy. Besides, objective ophthalmologic data allowed us to subdivide each group into two subtypes. Based on these findings, we have drawn decisional flowcharts directing the molecular analysis of LCA genes in a given case. These flowcharts will hopefully lighten the heavy task of genotyping new patients but only if one has access to the most precise clinical history since birth.

  8. Current advance in genetics and clinical phenotype of Leber congenital amaurosis%Leber先天性黑矇致病基因及相关临床表型研究进展

    Institute of Scientific and Technical Information of China (English)



    Leber congenital amaurosis (LCA) is one of the main inherited retinal diseases causing congenital blindness.LCA is also characterized by genetic heterogeneity and variable clinical phenotypes.Recent years,a lot of molecular genetic studies related with its pathogenesis have been performed.So far,20 causative genes have been identified that account for LCA.Some correlations between genotype and clinical phenotype have also been found.Those specific clinical manifestations may help to identify the mutant gene that causes the LCA.This review summarized the causal genes,their roles in the pathogenesis of LCA,coupled with relationship between specific gene and Corresponding phenotype,which will assist the clinician in patient diagnosis and counseling.%Leber先天性黑矇(LCA)是导致先天性盲的主要遗传性视网膜疾病,具有遗传异质性与临床表型多样性的特点.近年来其分子遗传学研究成为国内外热点,相继明确了20个与LCA相关的致病基因.多项研究表明LCA的基因型和临床表型之间存在关联,了解不同致病基因对应的临床表型特点有助于致病基因的筛查.就当前发现的LCA致病基因、可能的发病机制以及特定基因型与临床表型的关系进行综述,以期有助于临床诊断和咨询.

  9. 'Crescendo' transient ischemic attacks: clinical and angiographic correlations. (United States)

    Rothrock, J F; Lyden, P D; Yee, J; Wiederholt, W C


    Forty-seven consecutive patients presenting acutely with repetitive symptoms indicative of anterior circulation ischemia ("crescendo" transient ischemic attacks) were evaluated to identify clinical features that might reliably predict the presence of significant stenosis, ulceration, or both in the presumably symptomatic internal carotid artery. Angiographic or intraoperative correlation was obtained in all patients, and 26 (55%) were found to have anatomically significant disease. Of 20 patients with signs or symptoms suggestive of cortical ischemia, amaurosis fugax, or both, 17 (85%) had "positive" angiograms; of 18 with numbness/weakness only, 9 (50%) had positive angiograms; of 9 whose symptoms suggested lacunar ischemia, none had positive angiograms.

  10. Akut glaukom efter endarterektomi af arteria carotis interna

    DEFF Research Database (Denmark)

    Lindholt, Jes Sanddal; Klaerke, A


    A 71 year-old woman had 85% and 60% stenoses of the right and left internal carotid arteries, respectively. Right-sided endarterectomy was performed because of amaurosis fugax. Two days postoperatively, she developed classical symptoms and signs of acute glaucoma. Right-sided acute angle closure...... glaucoma was diagnosed by tonometry and gonioscopy, and treated with laser-iridectomy. The patient was discharged two days later without neurological or ophthalmological deficits. Manifest acute glaucoma postoperatively seems never to have been reported. However, the choroid is not autoregulated...

  11. Outcome of carotid endarterectomy for acute neurological deficit. (United States)

    Mussa, Firas F; Aaronson, Nicole; Lamparello, Patrick J; Maldonado, Thomas S; Cayne, Neal S; Adelman, Mark A; Riles, Thomas S; Rockman, Caron B


    We reviewed our experience with urgent carotid intervention in the setting of acute neurological deficits. Between June 1992 and August 2008, a total of 3145 carotid endarterectomies (CEA) were performed. Twenty-seven patients (<1.0%) were categorized as urgent. The mean age was 74.1 years (range 56-93 years) with 16 (60%) men, and 11 (40%) women, Symptoms included extremity weakness or paralysis (n=13), amaurosis fugax (n=6), speech difficulty (n=2), and syncope, (n=3). Three patients exhibited a combination of these symptoms. Three open thrombectomy were performed. Regional anesthesia was used in 13 patients (52%). Seventeen patients (67%), required shunt placement. At 30-days, 2 patient (7%) suffered a stroke, and 1 (4%) died. Urgent CEA can be performed safely. A stroke rate of 7% is acceptable in those who may otherwise suffer a dismal outcome without intervention.

  12. Embolic and nonembolic transient monocular visual field loss: a clinicopathologic review. (United States)

    Petzold, Axel; Islam, Niaz; Hu, Han-Hwa; Plant, Gordon T


    Transient monocular blindness and amaurosis fugax are umbrella terms describing a range of patterns of transient monocular visual field loss (TMVL). The incidence rises from ≈1.5/100,000 in the third decade of life to ≈32/100,000 in the seventh decade of life. We review the vascular supply of the retina that provides an anatomical basis for the types of TMVL and discuss the importance of collaterals between the external and internal carotid artery territories and related blood flow phenomena. Next, we address the semiology of TMVL, focusing on onset, pattern, trigger factors, duration, recovery, frequency-associated features such as headaches, and on tests that help with the important differential between embolic and non-embolic etiologies.

  13. Novel compound heterozygous NMNAT1 variants associated with Leber congenital amaurosis

    DEFF Research Database (Denmark)

    Siemiatkowska, Anna M; van den Born, L Ingeborgh; van Genderen, Maria M;


    and associated phenotypes in different types of inherited retinal dystrophies. METHODS: DNA samples of 161 patients with LCA without genetic diagnosis were analyzed for variants in NMNAT1 using Sanger sequencing. Variants in exon 5 of NMNAT1, which harbors the majority of the previously identified mutations......, were screened in 532 additional patients with retinal dystrophies. This cohort encompassed 108 persons with isolated or autosomal recessive cone-rod dystrophy (CRD), 271 with isolated or autosomal recessive retinitis pigmentosa (RP), and 49 with autosomal dominant RP, as well as 104 persons with LCA......: Although macular atrophy can occur in LCA and CRD, no NMNAT1 mutations were found in the latter cohort. NMNAT1 variants were also not found in a large group of patients with sporadic or autosomal recessive RP. The enrichment of p.E257K in a heterozygous state in patients with LCA versus controls suggests...

  14. CrxRdy Cat: A Large Animal Model for CRX-Associated Leber Congenital Amaurosis (United States)

    Occelli, Laurence M.; Tran, Nicholas M.; Narfström, Kristina; Chen, Shiming; Petersen-Jones, Simon M.


    Purpose Mutations in the retinal transcription factor cone-rod homeobox (CRX) gene result in severe dominant retinopathies. A large animal model, the Rdy cat, carrying a spontaneous frameshift mutation in Crx, was reported previously. The present study aimed to further understand pathogenesis in this model by thoroughly characterizing the Rdy retina. Methods Structural and functional changes were found in a comparison between the retinas of CrxRdy/+ kittens and those of wild-type littermates and were determined at various ages by fundus examination, electroretinography (ERG), optical coherence tomography, and histologic analyses. RNA and protein expression changes of Crx and key target genes were analyzed using quantitative reverse-transcribed PCR, Western blot analysis, and immunohistochemistry. Transcription activity of the mutant Crx was measured by a dual-luciferase transactivation assay. Results CrxRdy/+ kittens had no recordable cone ERGs. Rod responses were delayed in development and markedly reduced at young ages and lost by 20 weeks. Photoreceptor outer segment development was incomplete and was followed by progressive outer retinal thinning starting in the cone-rich area centralis. Expression of cone and rod Crx target genes was significantly down-regulated. The mutant Crx allele was overexpressed, leading to high levels of the mutant protein lacking transactivation activity. Conclusions The CrxRdy mutation exerts a dominant negative effect on wild-type Crx by overexpressing mutant protein. These findings, consistent with those of studies in a mouse model, support a conserved pathogenic mechanism for CRX frameshift mutations. The similarities between the feline eye and the human eye with the presence of a central region of high cone density makes the CrxRdy/+ cat a valuable model for preclinical testing of therapies for dominant CRX diseases. PMID:27427859

  15. Fifty-eight cases of ocular ischemic diseases caused by carotid artery stenosis

    Institute of Scientific and Technical Information of China (English)

    LUO Rong-jiang; LIU Shao-rui; LI Xiao-min; ZHUO Ye-hong; TIAN Zhen


    Background The blood supply to the eye comes from the retinal central vascular system of the ophthalmic artery and the ciliary vascular system. The ophthalmic artery stems from the ipsilateral internal carotid artery. If occlusion or stenosis occurs in the carotid artery, the blood perfusion to the ophthalmic artery becomes insufficient, leading to signs and symptoms of anterior and posterior ocular ischemia. The objective of this study was to evaluate the clinical characteristics and risk factors of ocular ischemic diseases caused by carotid artery stenosis.Methods This study was a retrospective review of 145 patients with carotid artery stenosis. Fifty-eight patients who had symptoms of ocular ischemic disease caused by carotid artery stenosis formed group A and the other 87 patients who only had carotid artery stenosis formed group B. We analyzed the causes and course of disease, and relative risk factors,by comparing the two groups.Results The degree of carotid artery stenosis in group A was higher than that in group B. And group A had a greater decrease of ophthalmic artery flow. Male, hypertension, hyperlipidemia, and smoking were significantly related to carotid artery stenosis. Amaurosis fugax was the most common ocular symptom in group A. The ocular ischemic diseases mainly included ischemic optic neuropathy, central/branch retinal artery occlusion, ophthalmoplegia externa, and ocular ischemic syndrome.Conclusions Carotid artery stenosis correlates with ocular ischemic diseases. Ophthalmologists must observe for ocular symptoms, which were the onset symptoms in some patients.

  16. [Hypercoagulable workup in ophthalmology. When and what]. (United States)

    Muñoz-Negrete, F J; Casas-Lleras, P; Pérez-López, M; Rebolleda, G


    Most ophthalmologic disorders secondary to hypercoagulabe state are due to the confluence of congenital and adquired factors. A systematic workup is mandatory. Most of congenital coagulation disorders cause venous trombosis and are inherited autosomal dominantly. In order of frequency these are factor V Leiden mutation (activated protein C resistance), G20210A mutation of the prothrombin gen and protein C, protein S, and antithrombin III deficiencies. Sickle cell anemia can determine arerial and venous thrombosis. In relation with arterial occlusion, the markers most frequently involved are homcysteine fasting levels and the markers of antiphospholipid antibody syndrome. Both of them can also determine venous thrombosis. Several acquired factors can lead to hypoercoagulable state, especially hyperhomocysteinemia, antiphospholipid antibody syndrome, hepatic disease, alcohol and tobacco intake, oral contraceptives, immobilization, surgeries and malignancies. In central venous occlusion is only necessary to rule out hyperhomocysteinemia and antiphospholipid antibody syndrome in young patients without known risk factors. In central artery occlusion, hypercoagulable workup is only recommended for patients less than 50 years-old with unknown emboli source. In this cases protein C, protein S, and antithrombin III deficiencies, homocystein, sickle cell disease and antiphospholipid antibody syndrome will ruled out. In non arteritic ischemic optic neuropathy hypercoagulable work up is not necessary. In amaurosis fugax without known emboli source, it is recommended to rule out etiologies of arterial occlusion, especially antithrombin III deficiencies, homocystein, sickle cell disease and antiphospholipid antibody syndrome.

  17. Spontaneous internal carotid dissection in a 38-year-old woman: a case report

    Directory of Open Access Journals (Sweden)

    Kareem Abed


    Full Text Available This case report describes a patient found to have amaurosis fugax as a result of non-traumatic internal carotid dissection. Monocular blindness can be due to multiple causes including keratitis, acute glaucoma, vitreous hemorrhage, uveitis, retinal vascular occlusion, retinal detachment, optic neuropathy, trauma, or vascular malformations. In the setting of headache, neck pain, and an otherwise normal ophthalmic examination, this case report highlights the importance of recognizing transient ischemic attack and carotid artery dissection in the differential diagnosis. To further clarify the diagnosis, carotid ultrasound may aid diagnosis as was seen in this case, where decreased internal carotid artery velocities were found and subsequent CT angiography of the neck confirmed a diagnosis of carotid dissection. If a dissection is present, progression of symptoms may indicate impending cerebral infarction and warrant immediate attention. Antiplatelet therapy is the first-line treatment with anticoagulation, thrombolysis, and surgery reserved for cases of recurrent, progressive symptomatic episodes. Surgical options include endovascular repair such as angioplasty, stent placement, embolization, surgical revascularization, and bypass.

  18. Venous Thromboembolism and Cerebrovascular Events in Patients with Giant Cell Arteritis: A Population-Based Retrospective Cohort Study.

    Directory of Open Access Journals (Sweden)

    Alberto Lo Gullo

    Full Text Available To investigate the incidence of venous thromboembolism (VTE and cerebrovascular events in a community-based incidence cohort of patients with giant cell arteritis (GCA compared to the general population.A population-based inception cohort of patients with incident GCA between January 1, 1950 and December 31, 2009 in Olmsted County, Minnesota and a cohort of non-GCA subjects from the same population were assembled and followed until December 31, 2013. Confirmed VTE and cerebrovascular events were identified through direct medical record review.The study population included 244 patients with GCA with a mean ± SD age at diagnosis of 76.2 ± 8.2 years (79% women and an average length of follow-up of 10.2 ± 6.8 years. Compared to non-GCA subjects of similar age and sex, patients diagnosed with GCA had a higher incidence (% of amaurosis fugax (cumulative incidence ± SE: 2.1 ± 0.9 versus 0, respectively; p = 0.014 but similar rates of stroke, transient ischemic attack (TIA, and VTE. Among patients with GCA, neither baseline characteristics nor laboratory parameters at diagnosis reliably predicted risk of VTE or cerebrovascular events.In this population-based study, the incidence of VTE, stroke and TIA was similar in patients with GCA compared to non-GCA subjects.

  19. Dissection of internal carotid artery presenting as isolated ischaemic optic neuropathy

    Directory of Open Access Journals (Sweden)

    Serdar Oruc


    Full Text Available Carotid artery dissections are one of the important reasons of cerebrovascular events that are observed before the age of 45. Besides the local findings such as head, neck and face pains, Horner syndrome findings, pulsatile tinnitus and cranial nerve involvements, some other symptoms such as ischemic stroke, transient ischemic attacks and amaurosis fugax can also be observed in the approximately three quarters of patients. Ischemic optic neuropathy may be seen as %4 in the carotid artery dissections and it mostly accompanies other ischemic local symptoms. It is rare to observe the ischemic optic neuropathy as the first and unique finding in the carotid artery dissections. In this study, a 55 year old male patient with carotid artery dissection was represented. He did not have any other complaint, except the sudden unilateral visual loss and he was sent to our clinics from the opthalmology clinics in order to search for the etiology of ischemic optic neuropathy. It should be kept in mind that there can be a possibility to have carotid artery dissections in patients with unilateral visual loss.

  20. The Application of Topical Anesthesia Combined with Subconjunctival Anesthesia for Glaucoma Surgery

    Institute of Scientific and Technical Information of China (English)

    Shengsong Huang; Minbin Yu; Jie Lian; Min Fan; Changyu Qiu


    Purpose: To evaluate the feasibility, reliability and analgesia effect of topical anesthesia combined with subconjunctival anesthesia in anti-glaucomatous surgery.Methods: Two hundred and four cases (357 eyes) underwent anti-glaucomatous surgeries under topical anesthesia with 0.5% Alcaine eye drops combined with subconjunctival anesthesia with 2% Lidocaine. The analgesic effect was analysed with visual analogue pain scale.Results: Among all of 357 eyes, 62 eyes underwent peripheral iridectomy, 67 eyes underwent simple trabeculectomy, 167 eyes underwent compound brabeculectomy and 12 eyes nonpenetrating trabecular surgery. The effects of anesthesia were as follows: 304 eyes(85.2%) were painless (Grade I ), 50 eyes (14.0%) were slight painful (Grade Ⅱ ), and 3 eyes (0.8%) were more painful (Grade Ⅲ ) during surgery. And no severe complications were observed in all the cases during surgery and postoperatively. Amaurosis fugax was not observed in the glaucoma patients at the late stage with narrow visual fields and poor visual ability.Conclusion: Topical anesthesia combined with subconjunctival anesthesia is effective,safe and simple anesthesia alternative in routine anti-glaucomatous surgery, especially for the glaucoma patients at the late stage with narrow visual fields and poor visual ability. It is worthy of being applied widely.

  1. The Protective Effects of Lycium Barbarum Polysaccharides on Transient Retinal Ischemia

    Directory of Open Access Journals (Sweden)

    Di Yang


    Full Text Available Retinal ischemia/reperfusion (I/R injury leads to irreversible neuronal death, glial activation, retinal swelling and oxidative stress. It is a common feature in various ocular diseases, such as glaucoma, diabetic retinopathy and amaurosis fugax. In the present study, we aimed to evaluate the effects of Lycium Barbarum Polysaccharides (LBP in a murine retinal I/R model. Mice were orally treated with either vehicle (PBS or LBP (1mg/kg daily for 1 week before induction of retinal ischemia. Retinae were collected after 2 hours ischemia and 22 hours reperfusion. Paraffin-embedded sections were prepared for immunohistochemical analyses. Significantly fewer viable cells were found in vehicle-treated retinae comparing to LBP group. This finding was further confirmed by TUNEL assay where significantly fewer apoptotic cells were identified in LBP-treated retinae. Additionally, retinal swelling induced by retinal I/R injury in the vehicle-treated group was not observed in LBP-treated group. Moreover, intense GFAP immunoreactivity and IgG extravasation were observed in vehicle-treated group but not in LBP treated group. The results showed that pre-treatment with LBP was protective in retinal I/R injury via reducing neuronal death, apoptosis, retinal swelling, GFAP activation and blood vessel leakage. LBP may be used as a preventive agent for retinal ischemia diseases.

  2. The CHAT classification of stroke. (United States)

    Bernstein, E F; Browse, N L


    Current terminology for clinical episodes relating to stroke is inconsistent and unclear, does not permit inclusion of data regarding the location and magnitude of extracranial and intracerebral arterial disease, does not coincide with existing classifications in Europe, and characterizes a hemispheric entity only, as opposed to a global description including prior symptoms in both hemispheres. A new classification system (CHAT) has been designed to deal with these problems, including the current clinical presentation, historical clinical episodes, the site and pathologic type of arterial disease, and information regarding abnormalities of the brain. Using this system, a retrospective review of 480 consecutive carotid endarterectomies is presented, demonstrating the advantages of the CHAT classification. Data include a significant difference in the probability of survival after carotid endarterectomy for asymptomatic stenosis in patients with prior symptoms on the opposite side, as well as a significant difference in the probability of stroke-free survival between patients with amaurosis fugax and those with prior carotid cortical symptoms (TIAs) as the presenting clinical condition. The CHAT classification is suggested as a significant advance in the reporting of all surgical cerebrovascular disease experience, and has particular implications for the current randomized trials between medical and surgical therapy for carotid artery disease.

  3. Asymptomatic carotid stenosis: What we can learn from the next generation of randomized clinical trials

    Directory of Open Access Journals (Sweden)

    Mark N Rubin


    Full Text Available Stroke remains an exceedingly incident and prevalent public health burden across the globe, with an estimated 16 million new strokes per annum and prevalence over 60 million, and extracranial internal carotid artery atherosclerotic disease is an important risk factor for stroke. Randomized trials of surgical treatment were conducted (North American Symptomatic Carotid Endarterectomy Trial, European Carotid Surgery Trial and demonstrated efficacy of carotid endarterectomy for secondary prevention of stroke in patients with cerebrovascular events (e.g. ipsilateral stroke, transient ischemic attack, and/or amaurosis fugax attributable to a diseased artery with 50–99% stenosis. Therapeutic clarity, however, proved elusive with asymptomatic carotid artery disease. Asymptomatic Carotid Atherosclerosis Study (ACAS, Asymptomatic Carotid Surgery Trial, and Veterans Affairs Cooperative Study (VACS suggested only modest benefit from surgical intervention for primary stroke prevention and the best medical therapy at the time of these trials is not comparable to modern medical therapy. ACT-1, Asymptomatic Carotid Surgery Trial-2, Stent-Protected Angioplasty in asymptomatic Carotid artery stenosis versus Endarterectomy Trial-2, European Carotid Surgery Trial-2, Carotid Revascularization Endarterectomy Versus Stenting Trial-2 are trials that are recent, ongoing, or in development that include diverse populations across Europe and North America, complementary trial designs, and a collaborative spirit that should provide clinicians with evidence that informs best clinical practice for asymptomatic carotid artery disease.

  4. Varied presentations of moyamoya disease in a tertiary care hospital of north-east India

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    Papori Borah


    Full Text Available Introduction: Moyamoya disease is a chronic progressive cerebrovascular disorder, characterized by stenosis or occlusion of bilateral internal carotid arteries (ICAs, anterior cerebral arteries (ACAs and middle cerebral arteries (MCAs, accompanied by a collateral network of vessels formed at the base of the brain. Ischemia and intracranial hemorrhage are the common typical manifestations. However moyamoya disease has been associated with atypical presentations like headache, seizures and involuntary movements. Although frequently reported from Asian countries like Japan, China and Korea, only few studies reported on clinical manifestations of moyamoya disease from India. Objectives: To study the varied presentations of moyamoya disease in a tertiary care hospital of north-east India. Material and Methods: Relevant investigations were done to rule out other causes of moyamoya syndrome. Results: We report 6 cases of moyamoya disease with varied presentations from a tertiary care referral government hospital. Case 1, 2 and 6 presented with alternating hemiparesis. Case 3 had amaurosis fugax. Case 4 had history suggestive of ischemic stroke and presented with hemichorea. Case 4 had focal seizure as the only manifestation. Cases 4 and 5 notably had stenosis of posterior cerebral artery (PCA in addition to stenosis of bilateral ICAs, ACAs and MCAs. Conclusion: Owing to its low incidence in India, moyamoya disease is easily overlooked as a possible diagnosis. However, because of its progressive nature, it is imperative to diagnose this disease early and offer surgical treatment to the patients.

  5. Recent advances in early-onset severe retinal degeneration: more than just basic research?

    DEFF Research Database (Denmark)

    Preising, M. N.; Heegaard, S.


    ophthalmology, Leber's congenital amaurosis, phenotype, gene therapy, retina, degeneration, rewiew......ophthalmology, Leber's congenital amaurosis, phenotype, gene therapy, retina, degeneration, rewiew...

  6. Orbital Osteoma With Gaze-Evoked Amaurosis%眶骨瘤伴凝视诱发黑蒙

    Institute of Scientific and Technical Information of China (English)

    Patrick Sibony; Maisie Shindo


    1例54岁 女性,右眼反复发作无痛性凝视诱发黑蒙3个月。在右眼外转20秒内,视野很快由周边向中心缩小。当恢复到第一眼位时,其视功能在30秒内又恢复正常。有鼻窦病史而无其他病史。

  7. Amaurose bilateral por menigoencefalite criptocócica: relato de caso Bilateral amaurosis due to cryptococcus meningoencephalitis: case report

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    Ricardo Evangelista Marrocos de Aragão


    Full Text Available Meningoencefalite criptocócica é infecção causada por um fungo denominado Cryptococcus neoformans. Duas formas são conhecidas: variação gattii e neoformans. A infecção antes da puberdade é rara. Cerca de metade dos pacientes apresentam algum estado imunossupressivo. O papiledema está presente em um terço dos pacientes por ocasião do diagnóstico. Relatamos um caso de meningoencefalite por criptococose em paciente de oito anos de idade, sem relato de doenças prévias, que evoluiu com amaurose bilateral. O diagnóstico foi confirmado por detecção do C. neoformans, var. gattii. O paciente foi tratado com anfotericina B e dexametasona. Na literatura existem poucos relatos de perda visual permanente após meningite por criptococose. A existência de um protocolo para tratamento de pacientes com papiledema é um fator determinante para evitar a perda visual.Cryptococcal meningitis is caused by the yeast Cryptococcus neoformans. Two varieties are recognized: var. gattii and var. neoformans. It is usually associated with immunosuppressive states, particularly HIV infection. Cryptococcal infection of the central nervous system is uncommon in immunocompetent children and difficult to diagnose. Ocular complications are common. Optic disc swelling was found in 33%. The following report describes a case of meningitis caused by C. neoformans var. gattii in an 8 year-old immunocompetent child who developed optic atrophy. The patient was treated with amphotericin B associated with corticosteroids. Possible therapeutic strategies aimed at reducing visual loss in cryptococcal meningitis have great importance to avoid this important morbidity.

  8. Update on the evaluation of transient vision loss

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    Pula JH


    Full Text Available John H Pula,1 Katherine Kwan,2 Carlen A Yuen,3 Jorge C Kattah4 1Department of Neurology, 2Department of ophthalmology, NorthShore University HealthSystem, Evanston IL, USA; 3University of Illinois College of Medicine at Peoria, 4Department of Neurology, University of Illinois College of Medicine at Peoria, Peoria, IL, USA Abstract: Transient vision loss may indicate underlying vascular disease, including carotid occlusion and thromboembolism, or it may have a more benign etiology, such as migraine or vasospasm. This review focuses on the differential diagnosis and workup of patients presenting with transient vision loss, focusing on several key areas: the relationship to thromboembolic vascular disease, hypercoagulable testing, retinal migraine, and bilateral vision loss. The objective is to provide the ophthalmologist with information on how to best manage these patients. Thromboembolic etiologies for transient vision loss are sometimes managed with medications, but when carotid surgery is indicated, earlier intervention may prevent future stroke. This need for early treatment places the ophthalmologist in the important role of expediting the management process. Hospital admission is recommended in patients presenting with transient symptoms within 72 hours who meet certain high-risk criteria. When the cause is giant cell arteritis, ocular ischemic syndrome, or a cardioembolic source, early management of the underlying condition is equally important. For nonthromboembolic causes of transient vision loss such as retinal migraine or retinal vasospasm, the ophthalmologist can provide reassurance as well as potentially give medications to decrease the frequency of vision loss episodes. Keywords: transient vision loss, TVL, amaurosis fugax, retinal migraine, ocular migraine, retinal vasospasm

  9. Preoperative White Matter Lesions Are Independent Predictors of Long-Term Survival after Internal Carotid Endarterectomy

    Directory of Open Access Journals (Sweden)

    Niku Oksala


    Full Text Available Background: Cerebral white matter lesions (WMLs predict long-term survival of conservatively treated acute stroke patients with etiology other than carotid stenosis. In carotid endarterectomy patients, WMLs are associated with severe carotid stenosis and unstable plaques, with the risk of perioperative complications and with increased 30-day perioperative risk of death. However, no data exist on their effect on postoperative long-term survival, a factor important when considering the net benefit from carotid endarterectomy. Whether this effect is independent of classical risk factors and indications for surgery is not known either. We hypothesized that WMLs could be evaluated from preoperative routine computed tomography (CT scans and are predictors of postoperative survival, independent of classical cardiovascular risk factors, indication category and degree of carotid stenosis. Methods: A total of 353 of 481 (73.4% consecutive patients subjected to carotid endarterectomy due to different indications, i.e. asymptomatic stenosis (n = 28, 7.9%, amaurosis fugax (n = 52, 14.7%, transient ischemic attack (n = 135, 38.2% or ischemic stroke (n = 138, 39.1%, from prospective vascular registries during the years 2001-2010 with digital preoperative CT scans, were included in the study. WMLs were rated by a radiologist (Wahlund criteria in a blinded fashion. Internal carotid artery (ICA stenoses were angiographically graded (Results: WML severity could be assessed with a substantial intraobserver agreement (Spearman's rho 0.843, p Conclusions: WMLs in a preoperative CT scan provide a substantially reliable estimate of postoperative long-term survival of carotid endarterectomy patients independent of currently used criteria, i.e. cardiovascular risk factors, indication category and degree of ipsilateral ICA stenosis.

  10. Dissektion der Arteria carotis als Ursache ischämischer zerebrovaskulärer Ereignisse - Fallberichte und Diskussion

    Directory of Open Access Journals (Sweden)

    Tentschert S


    Full Text Available Dissektionen der kraniozervikalen Gefäße, inbesondere der Arteria carotis, zählen zu den häufigsten Ursachen ischämischer zerebrovaskulärer Ereignisse bei jüngeren Patienten. Die ischämische Symptomatik wird durch eine Wühlblutung in die Gefäßwand verursacht, welche entweder zu einer Minderung des zerebralen Blutflusses und/oder zu einer lokalen Thrombosierung mit nachfolgender Embolisation führt. Karotisdissektionen können durch ein mechanisches Trauma hervorgerufen werden, sie entstehen aber auch spontan oder sind dann bei einem Teil der Patienten mit Bindegewebserkrankungen assoziiert. Zu den häufigsten Symptomen zählen Kopfschmerzen, zervikaler Schmerz und Horner-Syndrom. Die zerebrale Ischämie führt meist zu einer transienten ischämischen Attacke (TIA oder zu einem ischämischen Infarkt im Stromgebiet der Arteria cerebri media der betroffenen Seite. Auch eine Amaurosis fugax kann auftreten. Trotz neuer technischer Möglichkeiten stellen Dissektionen der hirnversorgenden Gefäße nach wie vor eine diagnostische Herausforderung dar. Die digitale Subtraktionsangiographie gilt derzeit noch als Goldstandard zur Diagnostik, wird aber in vielen Fällen zunehmend durch neue nichtinvasive bildgebende Verfahren ersetzt oder ergänzt. Stenose oder Verschluß des betroffenen Gefäßes bilden sich in den meisten Fällen innerhalb von zwei Monaten nach dem Ereignis zurück. Therapeutische Maßnahmen haben vor allem die Verhinderung embolischer Komplikationen zum Ziel. Die gegenständliche Arbeit soll anhand von Fallbeispielen und einer Literaturübersicht klinisch relevante Aspekte und Probleme bei Diagnostik und Therapie der Dissektion der Arteria carotis aufzeigen.

  11. Vasculitis cerebral cisticercosa y neuropatía óptica isquémica en una paciente con amaurosis unilateral y recuperación ad integrum


    Enríquez Coronel,Guillermo; Santos Marcial,Edgar; Cabrera Aldana,Eibar Ernesto


    La cisticercosis es una parasitósis bien conocida que puede causar una gran cantidad de síndromes. La neuropatía isquémica-óptica es una enfermedad de adultos cuyas causas principales son hipertensión arterial y la diabetes y la arteritis de células gigantes. Presentamos el caso de una estudiante de medicina de 22 años que presentó súbitamente pérdida de la visión en el ojo derecho y después completa ceguera. Los estudios demostraron múltiples cisticercos en el hemisferio derecho. Fue tratada...

  12. Advantage of whole exome sequencing over allele-specific and targeted segment sequencing in detection of novel TULP1 mutation in leber congenital amaurosis

    DEFF Research Database (Denmark)

    Guo, Yiran; Prokudin, Ivan; Yu, Cong


    by targeted segment sequencing of 61 regions in 14 causative genes was performed. Subsequently, exome sequencing was undertaken in the proband, unaffected consanguineous parents and two unaffected siblings. Bioinformatic analysis used two independent pipelines, BWA-GATK and SOAP, followed by Annovar and Snp...

  13. Disease: H00837 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available H00837 Leber congenital amaurosis (LCR) Leber congenital amaurosis (LCA) is a heter...M: 204000 204100 604232 604393 604537 613626 613829 613835 611755 613837 610612 612712 613341 613843 614186 PMID:20301475 Weleber... RG, Francis PJ, Trzupek KM Leber Congenital Amaurosis (1993...87:487-95 (2011) PMID:20399883 Cideciyan AV Leber congenital amaurosis due to RPE65 mutations and its treatment with gene therapy. Prog Retin Eye Res 29:398-427 (2010) ...


    Directory of Open Access Journals (Sweden)



    Full Text Available Retinal vein occlusion is the most common retinal occlusive disorder encountered by Ophthalmologists and is usually associated with a variable amount of visual loss. This is the second most common retinal vascular disease next to diabetic retinopathy. Liebreich initially described dramatic obstruction of veins as retinal apoplexy. Leber ( 1 (1877 reported the first case of BRVO and called it Hem orrhagic retinitis. RVO most commonly affects the venous blood supply of the entire retina (CRVO or a quadrant drained by one of the branches (BRVO or less commonly the superior or inferior half of the retina alone is affected (HCRVO. For discussion and management purpose RVO is broadly classified into six clinical entities includes (1 Non - ischemic CRVO (2 Ischemic CRVO (3 Non ischemic HCRVO (4Ischemic HCRVO (5 Major BRVO (6Macular BRVO. So much of confusion still exists regarding its natural histo ry, degree of severity, management and its progression. The clinical study of RVO is taken up mainly with a view to study the importance of systemic risk factors in etiopathogenisis of RVO, to study the clinical features and effectiveness of treatment in m odification of the natural course and complications of RVO. Depending on type of venous occlusion patient may present with loss of central vision frequently noticed on waking up in the morning, or field contraction, erythropsia, floates, black spots. Episo des of amaurosis fugax lasts for minutes to hours may be present. There may be metamor - phopsia. Signs of decreased visual acuty, RAPD, visual field defects are observed. Fundus picture shows Retinal hemorrhages distributed based on type of venous occlusion . In ischemic CRVO the picture shows “berries on a twig”. Various sequel & complications include macular edema, anterior segment and retinal neovascularisation, vitreous hemorrhage, retinal detachment may be encountered. Various risk factors include Hypert ension, Diabetes, Hyper lipidemia, IHD

  15. Manifestaciones oftalmológicas de la enfermedad cerebrovascular Ophthalmological manifestations of cerebrovascular disease

    Directory of Open Access Journals (Sweden)

    J. Gállego


    Full Text Available El ojo constituye una diana para la enfermedad vascular. El estudio de la microcirculación retiniana constituye una oportunidad muy interesante para la valoración del riesgo vascular al conocer la relación existente entre los cambios vasculares en la retina y el riesgo de padecer un ictus. Es además una ventana excepcional para conocer mejor la fisiopatología de la microcirculación. La arteria oftálmica es la primera rama de la arteria carótida interna. La afectación ocular puede ser uni o bilateral. Los síntomas oculares o neuro-oftalmológicos son transitorios o persistentes y sus manifestaciones son muy heterogéneas abarcando alteraciones de la agudeza visual, trastornos de los campos visuales, síndromes oculomotores y manifestaciones clínicas corticales y subcorticales complejas. Su conocimiento puede resultar clave para instaurar las medidas preventivas pertinentes o establecer el correcto diagnóstico y la aproximación diagnóstica inmediata, tan importante en la atención de los procesos vasculares cerebrales.Transient or persistent loss of vision in one eye is a common and distinctive manifestation of occlusive vascular disease. Occasionally, both eyes are involved together or sequentially, with temporary or even permanent blindness. The internal carotid arteries supply blood to the organ of vision; therefore pathologies of those arteries caused by arteriosclerosis may have a direct influence on its functioning. The most common syndromes are temporary (amaurosis fugax or constant reduction of visual acuity. In fundus examination central retinal artery occlusion and branch retinal artery occlusion are the most common diagnosis, while retinal vein occlusion, anterior ischemic optic neuropathy, ocular ischemic syndrome are less common. There are many clinical ophtlamological manifestations due to vascular brain damage. Proper recognition and diagnosis of the disease may protect the patient against serious life

  16. Non-traumatic neurological emergencies: imaging of cerebral ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Grunwald, Iris; Reith, Wolfgang [Department of Neuroradiology, Saarland University Clinic, Homburg/Saar (Germany)


    Cardiovascular disease is the leading cause of death worldwide with almost one-third of all cardiovascular deaths ascribed to stroke. Imaging modalities, such as CT, MRI, positron emission tomography (PET), and single photon emission CT (SPECT) provide tremendous insight into the pathophysiology of acute stroke. Computed tomography is considered the most important initial diagnostic study in patients with acute stroke, because underlying structural lesions, such as tumor, vascular malformation, or subdural hematoma, can mimic stroke clinically. Diffusion-weighted imaging (DWI) has the ability to visualize changes in diffusion within minutes after the onset of ischemia and has become a powerful tool in the evaluation of patients with stroke syndrome. Territories with diffusion and perfusion mismatch may define tissues at risk, but with potential recovery. An alternative strategy with CT technology uses rapid CT for dynamic perfusion imaging, with similar goals in mind. Angiography can be performed in the hyperacute stage if thrombolytic therapy is being considered. Indications for diagnostic angiography include transient ischemic attacks in a carotid distribution, amaurosis fugax, prior stroke in a carotid distribution, a high-grade stenotic lesion in a carotid artery, acquiring an angiographic correlation of magnetic resonance angiography (MRA) or computed tomographic angiography (CTA) concerning stenotic findings. In 50% of all angiograms performed in the hyperacute stage, occlusion of a vessel is observed; however, the need for angiography has been made less necessary due to the improvements of MRA, duplex ultrasound, and CTA. Numerous etiologies can lead to infarction. In children, pediatric stroke is very uncommon. The most common cause is an embolus from congenital heart disease with right-to-left shunts. Also a dissection of large extracranial vessels may result in cerebral infarction, and although the brain is equipped with numerous venous drainage routes

  17. Moyamoya病相关眼部症状的临床分析%Clinical analysis of ocular presentations in moyamoya disease

    Institute of Scientific and Technical Information of China (English)

    张朝贵; 万金城; 瞿昌华; 杨华; 王朝华


    目的:探讨与Moyamoya病相关的眼部临床表现、发生机制及其临床意义。方法回顾性分析37例有眼部症状的Moyamoya病患者的临床资料。结果37例有眼部症状的Moyamoya病患者,单纯以眼部症状首发者8例,眼部症状与其它神经系统症状同时出现的29例;患者眼部症状主要表现为:一过性黑朦、偏盲、视力下降甚至丧失、视野缺损、瞳孔直接/间接对光反射消失、瞳孔大小异常、上睑下垂、眼球运动障碍、眼球疼痛。结论 Moyamoya病眼部症状多样,神经科医生和眼科医生均应掌握Moyamoya病的临床表现及其特点,对于有眼部症状的患者应及时做全面的检查,以免漏诊和误诊。%OBJECTIVE To explore the clinical manifestations and mechanism of ocular symptoms related to moyamoya disease. METHODS The clinical information was analyzed retrospectively in 37 moyamoya disease. RE-SULTS There were 8 patients examined to simply perform ocular manifestations, while 29 patients had ocular mani-festations accompanied by other neurologic symptoms. These ocular signs included amaurosis fugax, hemianopia, de-cline even loss of the visual ability, visual field defect, pupil direct/indirect light reflex, pupil size abnormal, ptosis, ocular dyskinesia and eye pain. CONCLUSIONS The symptoms of moyamoya disease are multiple, which required neurologic physician and ophthalmologist be proficient in the onset characteristics and clinical manifestation. The patients must be diagnosed and treated as soon as possible to avoid misdiagnosis and missed diagnosis, especially for patients with ocular signs.

  18. 容易误诊漏诊的硬脑膜动静脉瘘9例分析%Dural arteriovenous fistula with easily inaccurate or missed diagnosis: analysis of 9 cases

    Institute of Scientific and Technical Information of China (English)

    廖焕权; 王鸿轩; 陈红兵; 杨智云; 王莹; 贺涓涓; 尚文锦; 洪华


    目的 提高对容易误诊漏诊的硬脑膜动静脉瘘(dural arteriovenous fistula,DAVF)的诊断水平.方法 回顾性总结9例DAVF的临床资料,结合文献进行分析.结果 9例主要临床表现及误诊情况分别为:视朦或视力下降4例,无颅内高压症状,误诊为视神经炎、颅内结核感染或特发性颅内压增高;记忆力下降1例,误诊为病毒性脑炎;双下肢无力1例,误诊为急性脊髓炎、神经鞘瘤;反复头痛1例,误诊为偏头痛、特发性颅内压增高;反复抽搐1例,误诊为正常颅内压脑积水;饮水呛咳、吞咽困难1例,误诊为脑梗死.3例满足于静脉窦血栓的诊断而忽略了DAVF.所有病例影像学均漏诊,但如仔细观察仍可发现细微的血管形态改变,提示动静脉畸形.结论 DAVF临床表现缺乏特异性,加上临床及放射科医师对本病认识不足,诊断思路狭窄,造成本病误诊、漏诊率高.%Objective To improve the diagnostic capability of dural arteriovenous fistula(DAVF) which easily leads to inaccurate or missed diagnosis.Methods The clinical information of 9 cases of DAVF was summarized retrospectively, and analyzed with a literature review.Results The main clinical manifestations and misdiagnosis of 9 cases were: 4 cases presenting with only amaurosis fugax or vision loss without symptoms of increased intracranial pressure were misdiagnosed as optic neuritis,intracranial tuberculosis infection and idiopathic intracranial hypertension;1 case presenting with memory decline was misdiagnosed as viral encephalitis;1 case presenting with bilateral lower limbs weakness was misdiagnosed as acute myelitis and neurilemmoma; 1 case presenting with recurrent headache was misdiagnosed as migraine and idiopathic intracranial hypertension;1 case presenting with repeating seizures was misdiagnosed as normal intracranial pressure hydrocephalus;1 case presenting with choking water and swallowing difficulty was misdiagnosed as cerebral infarction.3

  19. A synopsis of the Malesian species of Kibara (Monimiaceae)

    NARCIS (Netherlands)

    Philipson, W.R.


    Thirty-nine species are recognized of which twenty-four are described as new ( K. bullata, K. carrii, K. chimbuensis, K. ferox, K. flagelliformis, K. fragrans, K. fugax, K. hartleyi, K. karengana, K. katikii, K. kostermansii, K. latifolia, K. leachii, K. macrantha, K. nitens, K. novobritanica, K. ob

  20. A synopsis of the Malesian species of Kibara (Monimiaceae)


    Philipson, W.R.


    Thirty-nine species are recognized of which twenty-four are described as new ( K. bullata, K. carrii, K. chimbuensis, K. ferox, K. flagelliformis, K. fragrans, K. fugax, K. hartleyi, K. karengana, K. katikii, K. kostermansii, K. latifolia, K. leachii, K. macrantha, K. nitens, K. novobritanica, K. oblongata, K. rosselensis, K. royenii, K. shungolensis, K. sleumeri, K. streimannii, K. sudestensis, and K. versteeghii) ). One new combination is made: K. oligocarpella (Kaneh. & Hatus.) Philipson, ...

  1. Inherited Retinal Degenerative Clinical Trial Network (United States)


    created military Vision Center of Excellence in NEER steering committee meetings and deliberations. References: 1. Cideciyan AV, Aleman TS, Boye SL, et...2008;105:15112-15117. 2. Hauswirth W, Aleman TS, Kaushal S, et al. Phase I Trial of Leber Congenital Amaurosis due to RPE65 Mutations by Ocular

  2. Union makes strength: a worldwide collaborative genetic and clinical study to provide a comprehensive survey of RD3 mutations and delineate the associated phenotype

    NARCIS (Netherlands)

    Perrault, I.; Estrada-Cuzcano, A.; Lopez, I.; Kohl, S.; Li, S.; Testa, F.; Zekveld-Vroon, R.; Wang, X.; Pomares, E.; Andorf, J.; Aboussair, N.; Banfi, S.; Delphin, N.; Hollander, A.I. den; Edelson, C.; Florijn, R.; Jean-Pierre, M.; Leowski, C.; Megarbane, A.; Villanueva, C.; Flores, B.; Munnich, A.; Ren, H.; Zobor, D.; Bergen, A.; Chen, R.; Cremers, F.P.M.; Gonzalez-Duarte, R.; Koenekoop, R.K.; Simonelli, F.; Stone, E.; Wissinger, B.; Zhang, Q.; Kaplan, J.; Rozet, J.M.


    Leber congenital amaurosis (LCA) is the earliest and most severe retinal degeneration (RD), and the most common cause of incurable blindness diagnosed in children. It is occasionally the presenting symptom of multisystemic ciliopathies which diagnosis will require a specific care of patients. Ninete

  3. Simultaneous Mutation Detection in 90 Retinal Disease Genes in Multiple Patients Using a Custom-designed 300-kb Retinal Resequencing Chip

    NARCIS (Netherlands)

    Booij, Judith C.; Bakker, Arne 1; Kulumbetova, Jamilia; Moutaoukil, Youssef; Smeets, Bert; Verheij, Joke; Kroes, Hester Y.; Klaver, Caroline C. W.; van Schooneveld, Mary; Bergen, Arthur A. B.; Florijn, Ralph J.


    Purpose: To develop a high-throughput, cost-effective diagnostic strategy for the identification of known and new mutations in 90 retinal disease genes. Design: Evidence-based study. Participants: Sixty patients with a variety of retinal disorders, including Leber's congenital amaurosis, ocular albi

  4. A Novel Nonsense Mutation in CEP290 Induces Exon Skipping and Leads to a Relatively Mild Retinal Phenotype

    NARCIS (Netherlands)

    Littink, Karin W.; Pott, Jan-Willem R.; Collin, Rob W. J.; Kroes, Hester Y.; Verheij, Joke B. G. M.; Blokland, Ellen A. W.; Miro, Marta de Castro; Hoyng, Carel B.; Klaver, Caroline C. W.; Koenekoop, Robert K.; Rohrschneider, Klaus; Cremers, Frans P. M.; van den Born, L. Ingeborgh; den Hollander, Anneke I.


    PURPOSE. To identify the genetic defect in a family with variable retinal phenotypes. The proband had a diagnosis of Leber congenital amaurosis (LCA), whereas her two cousins had an early-onset severe retinal dystrophy (EOSRD) with useful vision. A distant family member had retinitis pigmentosa (RP)

  5. Comparison of selected species of Bipolaris, Drechslera and Exserohilum by random amplification of polymorphic DNA. (United States)

    Bakonyi, J; Pomázi, A; Fischl, G; Hornok, L


    Forty-six strains representing 15 species of Drechslera, five of Bipolaris and four of Exserohilum, as well as two formae of Drechslera teres were compared by RAPD analysis. Drechslera formed a large, heterologous group, while species of Bipolaris and Exserohilum were more closely related. Strong pair-wise affinities were observed between D. graminea and D. teres, D. tritici-repentis and D. bromi, D. siccans and D. biseptata, D. fugax and D. poae, B. sorghicola and B. zeicola, as well as between E. rostratum and E. turcicum.

  6. Horsfield's hawk-cuckoo nestlings simulate multiple gapes for begging. (United States)

    Tanaka, Keita D; Ueda, Keisuke


    Nestlings of some brood parasitic birds evict hosts' eggs and young soon after hatching, thereby avoiding discrimination by hosts while monopolizing parental care. Eviction carries a cost, however, because lone parasitic nestlings attract a reduced provisioning rate. Here we describe a form of visual signaling used by the evicting Horsfield's hawk-cuckoo (Cuculus fugax) to obtain sufficient food. The chick displays a gape-colored patch on the wing to the host parents as they deliver food, simulating the gaping display of more than one nestling.

  7. Leucosiid crabs (Crustacea: Decapoda: Brachyura) from Taiwan, with three new records. (United States)

    Shih, Yi-Jia; Ho, Ping-Ho; Chan, Tin-Yam


    Four leucosiid species from Taiwan are presented. Ebalia nudipes Sakai, 1963, with its male first gonopod figured for the first time. Galilia petricola Komai & Tsuchida, 2014, is recorded on the basis of a larger specimen, and distinguishing features with its only congener, G. narusei Ng & Richer de Forges, 2007, reappraised. Nursia rhomboidalis (Miers, 1879), previously known only from Japan, Korea, and mainland China, is also recorded from Taiwan. Myra fugax (Fabricius, 1798) is now formally recorded from Taiwan, and female characters identified to help separate the three known Taiwanese species of Myra.

  8. Leber先天性黑蒙

    Institute of Scientific and Technical Information of China (English)

    Neelakshi; Bhagat; 黎霞; 瞿佳


    "Leber先天性黑蒙(Leber’scongenital amaurosis,LCA)是一种出生后视力快速下降的致盲性眼病,该病的早期诊断存在一定困难,容易漏诊误诊。目前基因治疗LCA在临床上已经取得成功。"

  9. Novel Mutations in Two Saudi Patients with Congenital Retinal Dystrophy


    Leen Abu Safieh; Al-Otaibi, Humoud M.; Richard Alan Lewis; Igor Kozak


    To report novel mutations in two Saudi children with clinical features of Leber congenital amaurosis (LCA) and Alström syndrome. Case reports. Case 1 was a child with phenotypic features of LCA including oculodigital sign, bilateral enophthalmos, nystagmus, pale disc, and retinal changes. Direct sequencing of the coding sequence of GUCY2D revealed a missense mutation affecting highly conserved position (c. 743C > T; p.S248 L). Case 2 describes a girl with marked nystagmus, photophobia, and re...

  10. Hidden Genetic Variation in LCA9‐Associated Congenital Blindness Explained by 5′UTR Mutations and Copy‐Number Variations of NMNAT1


    Coppieters, Frauke; Todeschini, Anne Laure; Fujimaki, Takuro; Baert, Annelot; DE BRUYNE, MARIEKE; Van Cauwenbergh, Caroline; Verdin, Hannah; Bauwens, Miriam; Ongenaert, Maté; Kondo, Mineo; Meire, Françoise; Murakami, Akira; Veitia, Reiner A; Leroy, Bart; De Baere, Elfride


    ABSTRACT Leber congenital amaurosis (LCA) is a severe autosomal‐recessive retinal dystrophy leading to congenital blindness. A recently identified LCA gene is NMNAT1, located in the LCA9 locus. Although most mutations in blindness genes are coding variations, there is accumulating evidence for hidden noncoding defects or structural variations (SVs). The starting point of this study was an LCA9‐associated consanguineous family in which no coding mutations were found in the LCA9 region. Explori...

  11. Inherited Retinal Degenerative Disease Registry (United States)


    Eye Diseases Hereditary; Retinal Disease; Achromatopsia; Bardet-Biedl Syndrome; Bassen-Kornzweig Syndrome; Batten Disease; Best Disease; Choroidal Dystrophy; Choroideremia; Cone Dystrophy; Cone-Rod Dystrophy; Congenital Stationary Night Blindness; Enhanced S-Cone Syndrome; Fundus Albipunctatus; Goldmann-Favre Syndrome; Gyrate Atrophy; Juvenile Macular Degeneration; Kearns-Sayre Syndrome; Leber Congenital Amaurosis; Refsum Syndrome; Retinitis Pigmentosa; Retinitis Punctata Albescens; Retinoschisis; Rod-Cone Dystrophy; Rod Dystrophy; Rod Monochromacy; Stargardt Disease; Usher Syndrome

  12. To evaluate the composition and typing of carotid artery atherosclerotic plaque and the relationship between plaque morphology and clinical symptoms%MRI评估颈动脉粥样硬化斑块成分、类型及其与临床症状的相关性

    Institute of Scientific and Technical Information of China (English)

    罗南; 刘一; 范占明


    Objective To compare plaque morphology from patients with and without stroke symptoms, determine the relationship between carotid plaque morphology and stroke pathogenesis, and evaluate the warning function of high-field MR on early diagnosis of plaque. Methods Patients with carotid artery atherosclerotic plaque detected by B-mode ultrasonography were examined with MR imaging. Imaging was performed with a 3.0-T MR imager (Philips or GE) and a special 8-channel phased-array surface coil for carotid artery. The protocols include T1-, intermediate-, T2-, and post-contrast T1-weighted MR imaging, as well as three-dimensional time-of-flight (TOF) and MP-RAGE. All examinations were performed with a 14cm field of view, a matrix of 256 × 256 pixels,a 2-mm section thickness, and two acquired signals. An intersection space of -1 mm was used for three-dimensional TOF angiography and MP-RAGE, whereas no intersection space was used for MR imaging. Gadopentetate Dimeglumine was the contrast agent with the dosage of 0.1 mmol/Kg(0.2 ml/Kg)and injection speed of 0.7 ml/s. One observer recorded quantitative and morphologic information, which included measurement of the area of the lumen and main plaque components (calcification, hemorrhage, loose matrix ); fibrous cap status (thick, thin, or ruptured); reformed MR lesion type (types Ⅰ-Ⅷ) based on American Heart Association (AHA). Plaques associated with neurologic symptoms(transient ischemic attack, amaurosis fugax, or stroke appropriate to the distribution of the index carotid artery)and asymptomatic plaques were compared with Independent-sample T test on luminal stenosis, chi square test on occurrence rate of main plaque components and fibrous cap rupture respectively and regression analysis for the connection strength between plaque components and clinical symptoms. Results 64 carotid artery enrolled in the symptomatic group and 131 carotid artery enrolled in the asymptomatic group. Compared with asymptomatic plaques

  13. Chronic perineal pain: current pathophysiological aspects, diagnostic approaches and treatment. (United States)

    Andromanakos, Nikolaos P; Kouraklis, Grigorios; Alkiviadis, Kostakis


    Chronic perineal pain is the anorectal and perineal pain without underlying organic disease, anorectal or endopelvic, which has been excluded by careful physical examination, radiological and endoscopic investigations. A variety of neuromuscular disorders of the pelvic floor lead to the different pathological conditions such as anorectal incontinence, urinary incontinence and constipation of obstructed defecation, sexual dysfunction and pain syndromes. The most common functional disorders of the pelvic floor muscles, accompanied by perineal pain are levator ani syndrome, proctalgia fugax, myofascial syndrome and coccygodynia. In the diagnosis of these syndromes, contributing to a thorough history, physical examination, selected specialized investigations and the exclusion of organic disease with proctalgia is carried out. Accurate diagnosis of the syndromes helps in choosing an appropriate treatment and in avoiding unnecessary and ineffective surgical procedures, which often are performed in an attempt to alleviate the patient's symptoms.

  14. Moraea intermedia and M. vuvuzela (Iridaceae-Iridoideae, two new species from western South Africa, and some nomenclatural changes and range extensions in the genus

    Directory of Open Access Journals (Sweden)

    P. Goldblatt


    Full Text Available We describe two new species in the largely sub-Saharan genus Moraea Mill. (± 205 spp. from its centre of diversity in the winter rainfall region of southern Africa. Moraea intermedia, from north-central Namaqualand near Springbok, is a member of the small section Tubiflorae (now eight species, remarkable in its growth habit with a long basal intemode. leaves clustered at the first aerial node, and Moraea-type stamens and style branches but subequal tepals with very short claws that clasp only the base of the filament column. Moraea vuvuzela. a member of series Galaxia of the Galaxia group of the genus (now 17 species, has deeply fringed stigma lobes, filaments free in the upper 1 mm, ± prostrate, lanceolate leaves and. remarkable for the series, dark brown to purple markings near the base of the tepal limbs. In the unusually variable M.fugax, currently with two subspecies, new collections of subsp. fugax co-occurring but on different soils with subsp.  filicaulis, cast doubt on their current treatment as members of the same species. We now favour recognition of the diminutive subsp.filicaulis as a separate species, M. filicaulis. In the M iripetala group we recommend recognition of the early blooming M. punctata, described in 1892 and later subsumed in M. iripetala but readily distinguished by the long inner  tepals broader in the midline and short, relatively broad, plane rather than channelled leaves. We also report small but significant range extensions for M. barkerae, M. macrocarpa and M. tricolor.

  15. [Oclusion of upper ophthalmic vein--a case report]. (United States)

    Kácerik, M; Alexík, M; Lipková, B


    Thrombosis of upper ophthalmic vein is both rare and serious pathologic event. Authors present a case of isolated unilateral upper ophthalmic vein thrombosis in 76-year-old woman, who despite treatment ended with amaurosis and secondary neovascular glaucoma. In differential diagnosis authors focused on searching for inflammatory process of orbit with adjacent structures as well as local and general causes leading to venous thrombosis. None of these were proven; it was a rare case of a patient with isolated upper ophthalmic vein thrombosis.

  16. Dicty_cDB: Contig-U16564-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available iparum reticulocyte... 39 1.2 CP000939_2369( CP000939 |pid:none) Clostridium botulinum B1 str. O... 38 1.6 (Q4R3Q7) Leber...cilin-like protein (Leber congenital amaurosis 5-l... 38 1.6 AB169356_1( AB169356 |pid:none) Homo sapiens chromosome 21 segment... 38 1.6 BC043006_1( BC043006 |pid:none) Homo sapiens Leber con...omosome ... 38 1.6 ( O95447 ) RecName: Full=Lebercilin-like protein; AltName: Full=Le... 38 1.6 AL844506_148

  17. [Postoperative cortical blindness after right upper lung lobectomy]. (United States)

    Bausili, M; Abreu, S; Unzueta, M C; García Álvarez, M; Crespí, J; Moral, M V


    Changes in vision after non-ophthalmic surgery are a serious complication that can have devastating consequences due to its potential irreversibility. This not only leads to medical problems, but also legal ones. Many causes that affect sight during the peri-operative period have been identified, whether due to optic nerve damage or of extra-ocular origin (in the neuro-optic pathways and/or cerebral cortex). AU these may have a multifactorial origin, and there is still controversy as regards it pathogenesis and treatment. We present the case of a thoracic surgery patient who had a bilateral amaurosis in the post-operative period, which had a favourable outcome.

  18. 防除多花黑麦草等4种禾本科杂草的药剂活性测定%Biological activities of eight herbicides against four grass weeds of wheat fields

    Institute of Scientific and Technical Information of China (English)

    高兴祥; 李美; 房锋; 张悦丽; 齐军山


    为了系统研究多花黑麦草、早熟禾、碱茅和棒头草等4种小麦田禾本科杂草的防除药剂活性,在温室内采用盆栽法研究了8种除草剂对小麦田多花黑麦草等4种禾本科杂草的生物活性。结果表明,乙酰乳酸合成酶(ALS)抑制剂啶磺草胺对早熟禾有很好的防除效果,田间推荐剂量下防效达到93.06%(防效均为田间推荐剂量下,下同),对碱茅、多花黑麦草和棒头草的效果也较好,防效在82.82%~86.89%之间,另2种 ALS 抑制剂氟唑磺隆和甲基二磺隆对早熟禾的防效较好,在61.27%~86.71%之间,但对其他3种杂草碱茅、棒头草和多花黑麦草的防效很差,防效仅在10.47%~29.43%之间。乙酰辅酶 A 羧化酶(ACCase)抑制剂唑啉草酯、肟草酮和炔草酯对碱茅、棒头草和多花黑麦草的防效均较好,在85.41%~100.00%之间,但对早熟禾的防效均较差,在19.08%~60.69%之间;另一种 ACC 抑制剂精噁唑禾草灵对棒头草防效为99.60%,对碱茅和多花黑麦草防效分别为72.00%和55.00%,对早熟禾仅为16.18%;植物光合系统Ⅱ抑制剂异丙隆对早熟禾、棒头草和碱茅的防效均较好,田间推荐剂量下防效在88.15%~96.53%之间,对多花黑麦草的效果略差,为67.43%。%Pyroxsulam,flucarbazone-Na,pinoxaden,tralkoxydim and clodinafop-propargyl are newly registered herbicides in China.A glasshouse experiment was conducted to evaluate the efficacy of these herbicides,com-pared with several commonly used herbicides,on four grass weed species in wheat fields.Key results were:1) The acetolactate synthase (ALS)inhibiting herbicide pyroxsulam achieved 93.06% control on Poa annua and 82.82%-86.89% control on Puccinellia distans ,Lolium multiflorum ,Polypogon fugax (all herbicides ap-plied at recommended field dose rates).2)Other ALS inhibiting herbicides

  19. Reversão de amaurose por neuropatia óptica em orbitopatia de Graves após descompressão orbitária: relato de caso Reversal of blindness due to Graves' optic neuropathy after orbital decompression: case report

    Directory of Open Access Journals (Sweden)

    Valmor Rios Leme


    Full Text Available OBJETIVO: Descrever o caso de uma paciente portadora de orbitopatia de Graves com baixa visual no olho esquerdo há 9 meses e amaurose no direito há 20 dias secundária à neuropatia óptica. MÉTODOS: Foi realizada descompressão orbitária bilateral ínfero-medial por via transconjuntival. RESULTADOS: Após a cirurgia a paciente evoluiu lentamente com melhora progressiva da acuidade visual, obtendo 20/20 em ambos os olhos ao cabo de 10 meses. CONCLUSÕES: A descompressão orbitária é eficaz em restabelecer a visão em casos de amaurose por neuropatia óptica da orbitopatia de Graves com até 20 dias de instalação.PURPOSE: To describe a patient with Graves' orbitopathy who presented with loss of vision of the left eye for 9 months and amaurosis of the right eye for 20 days. METHODS: Bilateral inferomedial transnconjunctival orbital decompression was performed. RESULTS: After orbital decompression, vision slowly improved and ten months after the surgery the vision was normal in both eyes. CONCLUSIONS: Orbital decompression can reestablish optic nerve function at least 20 days after amaurosis.

  20. [Changes introduced into the recent International Classification of Headache Disorders: ICHD-III beta classification]. (United States)

    Belvis, Robert; Mas, Natàlia; Roig, Carles


    Introduccion. La Sociedad Internacional de Cefaleas (IHS) ha publicado la tercera edicion de la Clasificacion Internacional de las Cefaleas (ICHD-III beta), la guia diagnostica de las cefaleas mas utilizada en el mundo. Objetivo. Revisar las recientes aportaciones de la guia, explicando las nuevas entidades que en ella aparecen y comparando las entidades que han matizado sus criterios con sus criterios de la edicion precedente. Desarrollo. Hemos registrado multitud de matices en los criterios de practicamente todas las cefaleas y neuralgias de la clasificacion, pero las entidades que han experimentado mas matizaciones trascendentales son la migraña cronica, la cefalea asociada exclusivamente a la actividad sexual, las cefaleas neuralgiformes unilaterales de breve duracion, la cefalea diaria persistente de novo, la cefalea por abuso de medicacion sintomatica, el sindrome de cefalea y deficits neurologicos transitorios con pleocitosis linfocitaria. Las entidades nuevas mas destacables que se han incorporado son las cefaleas por presion externa, las cefaleas por crioestimulo, la cefalea numular, la cefalea atribuida a vuelos de avion y la cefalea atribuida a disreflexia autonomica. Tambien cabe destacar las nuevas cefaleas, aun no consideradas como entidades, que se incorporan al apendice, entre las que destacan la epicranea fugax, la migraña vestibular y los colicos infantiles. Conclusiones. La IHS recomienda utilizar ya la nueva clasificacion (ICHD-III beta), prescindiendo de la anterior clasificacion, en la asistencia, la docencia y la investigacion, asi como hacer la maxima difusion de esta nueva guia.

  1. Presacral abscess as a rare complication of sacral nerve stimulator implantation. (United States)

    Gumber, A; Ayyar, S; Varia, H; Pettit, S


    A 50-year-old man with intractable anal pain attributed to proctalgia fugax underwent insertion of a sacral nerve stimulator via the right S3 vertebral foramen for pain control with good symptomatic relief. Thirteen months later, he presented with signs of sepsis. Computed tomography (CT) and magnetic resonance imaging (MRI) showed a large presacral abscess. MRI demonstrated increased enhancement along the pathway of the stimulator electrode, indicating that the abscess was caused by infection introduced at the time of sacral nerve stimulator placement. The patient was treated with broad spectrum antibiotics, and the sacral nerve stimulator and electrode were removed. Attempts were made to drain the abscess transrectally using minimally invasive techniques but these were unsuccessful and CT guided transperineal drainage was then performed. Despite this, the presacral abscess progressed, developing enlarging gas locules and extending to the pelvic brim to involve the aortic bifurcation, causing hydronephrosis and radiological signs of impending sacral osteomyelitis. MRI showed communication between the rectum and abscess resulting from transrectal drainage. In view of the progressive presacral sepsis, a laparotomy was performed with drainage of the abscess, closure of the upper rectum and formation of a defunctioning end sigmoid colostomy. Following this, the presacral infection resolved. Presacral abscess formation secondary to an infected sacral nerve stimulator electrode has not been reported previously. Our experience suggests that in a similar situation, the optimal management is to perform laparotomy with drainage of the presacral abscess together with simultaneous removal of the sacral nerve stimulator and electrode.

  2. Diurnal and twenty-four hour patterning of human diseases: acute and chronic common and uncommon medical conditions. (United States)

    Smolensky, Michael H; Portaluppi, Francesco; Manfredini, Roberto; Hermida, Ramon C; Tiseo, Ruana; Sackett-Lundeen, Linda L; Haus, Erhard L


    The symptom intensity and mortality of human diseases, conditions, and syndromes exhibit diurnal or 24 h patterning, e.g., skin: atopic dermatitis, urticaria, psoriasis, and palmar hyperhidrosis; gastrointestinal: esophageal reflux, peptic ulcer (including perforation and hemorrhage), cyclic vomiting syndrome, biliary colic, hepatic variceal hemorrhage, and proctalgia fugax; infection: susceptibility, fever, and mortality; neural: frontal, parietal, temporal, and occipital lobe seizures, Parkinson's and Alzheimer's disease, hereditary progressive dystonia, and pain (cancer, post-surgical, diabetic neuropathic and foot ulcer, tooth caries, burning mouth and temporomandibular syndromes, fibromyalgia, sciatica, intervertebral vacuum phenomenon, multiple sclerosis muscle spasm, and migraine, tension, cluster, hypnic, and paroxysmal hemicranial headache); renal: colic and nocturnal enuresis and polyuria; ocular: bulbar conjunctival redness, keratoconjunctivitis sicca, intraocular pressure and anterior ischemic optic neuropathy, and recurrent corneal erosion syndrome; psychiatric/behavioral: major and seasonal affective depressive disorders, bipolar disorder, parasuicide and suicide, dementia-associated agitation, and addictive alcohol, tobacco, and heroin cravings and withdrawal phenomena; plus autoimmune and musculoskeletal: rheumatoid arthritis, osteoarthritis, axial spondylarthritis, gout, Sjögren's syndrome, and systemic lupus erythematosus. Knowledge of these and other 24 h patterns of human pathophysiology informs research of their underlying circadian and other endogenous mechanisms, external temporal triggers, and more effective patient care entailing clinical chronopreventive and chronotherapeutic strategies.

  3. Clinical features of unspecified functional bowel disorder in servicemen from a Chinese army unit

    Directory of Open Access Journals (Sweden)

    Xin YAO


    Full Text Available Objective To investigate clinical manifestation of unspecified functional bowel disorder (UFBD, the features of coexistence with functional gastrointestinal disorder (FGID and its relationship with psychological factors and sleep disturbance in the Chinese Army servicemen. Methods cFGIDs were diagnosed based on the Rome Ⅲ Modular Questionnaire. The subjects were 189 servicemen with UFBD (UFBD group and 372 without FGID (control group. All subjects completed symptom checklist 90 (SCL-90 and Pittsburgh Sleep Quality Index (PSQI questionnaire. Results 'Have to rush to the toilet when having a desire to defecate' was the most frequent symptom of UFBD (93.7%. More than one half of UFBD patients had the symptom 'a feeling of incomplete emptying as bowel movements' or 'straining during bowel movements'. Twenty-eight percent of UFBD subjects had combined FGID (namely cFGID. Among them, the most frequent was proctalgia fugax (7.9%, followed by cyclic vomiting syndrome (6.3%, functional fecal incontinence (6.3%, functional dyspepsia (4.8% and belching (4.8%. The UFBD group scored significantly higher than the control group in the global severity index (GSI and in all SCL-90 subscales (P0.05. Conclusion Pathogenesis of UFBD may be closely correlated with psychiatric and psychological factors and sleep disturbance. cFGID are associated with an increased severity of psychopathological features. DOI: 10.11855/j.issn.0577-7402.2017.01.15

  4. Prevalence and Diagnostic Spectrum of Generalized Retinal Dystrophy in Danish Children

    DEFF Research Database (Denmark)

    Bertelsen, Mette; Jensen, Hanne; Larsen, Michael;


    Abstract Purpose: The aim of the present population-based cross-sectional study was to examine the prevalence and diagnostic spectrum of generalized retinal dystrophy in Danish children. Methods: The Danish Registry for the Blind and Partially Sighted Children comprises all visually impaired......: Of the 1,204,235 Danish children aged 0-17 years on 1 October 2011, 2017 children were registered as visually impaired. Of these, 153 cases were attributed to generalized retinal dystrophy, corresponding to a prevalence of 13 per 100,000 children. The age-specific prevalence increased prominently...... dystrophy in Danish children is 13 per 100,000, which is a considerable increase compared to the 9.8 per 100,000 reported by Rosenberg in 1988. The prevalence of Leber congenital amaurosis, Usher syndrome, and Bardet-Biedl syndrome doubled, which may be explained by a documented history of consanguinity...

  5. [Gene therapy for hereditary ophthalmological diseases: Advances and future perspectives]. (United States)

    Chacón-Camacho, Óscar Francisco; Astorga-Carballo, Aline; Zenteno, Juan Carlos


    Gene therapy is a promising new therapeutic strategy that could provide a novel and more effective way of targeting hereditary ophthalmological diseases. The eye is easily accessible, highly compartmentalized, and an immune-privileged organ that gives advantages as an ideal gene therapy target. Recently, important advances in the availability of various intraocular vector delivery routes and viral vectors that are able to efficiently transduce specific ocular cell types have been described. Gene therapy has advanced in some retinal inherited dystrophies; in this way, preliminary success is now being reported for the treatment of Leber congenital amaurosis (LCA). This review will provide an update in the field of gene therapy for the treatment of ocular inherited diseases.

  6. Migraine with persistent aura in a Mexican patient: case report and review of the literature. (United States)

    San-Juan, O D; Zermeño, P F


    Persistent aura symptoms in patients with migraine are rare but well documented. The International Headache Society defines persistent aura without infarction as when the aura symptoms persist for > 1 week without radiographic evidence of infarction. The visual aura of migraine attacks has been explained by cortical spreading depression. We describe a case of a 28-year-old Mexican woman, who presented with persistent aura symptoms, and a literature review. The patient had a 24-year history of migraine headache. In November 2005 the patient had an attack which started with scintillating scotomas bilaterally associated with photopsias and amaurosis followed by migraine headache. All imaging studies were negative. The episode lasted 35 days and probably resolved with nimodipine therapy. Persistent aura symptoms are rare entities. This is the first case documented of a Mexican patient with persistent aura without infarction and probably resolved with nimodipine therapy.

  7. Gene therapy for mitochondrial diseases: Leber Hereditary Optic Neuropathy as the first candidate for a clinical trial. (United States)

    Cwerman-Thibault, Hélène; Augustin, Sébastien; Ellouze, Sami; Sahel, José-Alain; Corral-Debrinski, Marisol


    Mitochondrial disorders cannot be ignored anymore in most medical disciplines; indeed their minimum estimated prevalence is superior to 1 in 5000 births. Despite the progress made in the last 25 years on the identification of gene mutations causing mitochondrial pathologies, only slow progress was made towards their effective treatments. Ocular involvement is a frequent feature in mitochondrial diseases and corresponds to severe and irreversible visual handicap due to retinal neuron loss and optic atrophy. Interestingly, three clinical trials for Leber Congenital Amaurosis due to RPE65 mutations are ongoing since 2007. Overall, the feasibility and safety of ocular Adeno-Associated Virus delivery in adult and younger patients and consistent visual function improvements have been demonstrated. The success of gene-replacement therapy for RPE65 opens the way for the development of similar approaches for a broad range of eye disorders, including those with mitochondrial etiology such as Leber Hereditary Optic Neuropathy (LHON).

  8. Using Stem Cells to Model Diseases of the Outer Retina

    Directory of Open Access Journals (Sweden)

    Camille Yvon


    Full Text Available Retinal degeneration arises from the loss of photoreceptors or retinal pigment epithelium (RPE. It is one of the leading causes of irreversible blindness worldwide with limited effective treatment options. Generation of induced pluripotent stem cell (IPSC-derived retinal cells and tissues from individuals with retinal degeneration is a rapidly evolving technology that holds a great potential for its use in disease modelling. IPSCs provide an ideal platform to investigate normal and pathological retinogenesis, but also deliver a valuable source of retinal cell types for drug screening and cell therapy. In this review, we will provide some examples of the ways in which IPSCs have been used to model diseases of the outer retina including retinitis pigmentosa (RP, Usher syndrome (USH, Leber congenital amaurosis (LCA, gyrate atrophy (GA, juvenile neuronal ceroid lipofuscinosis (NCL, Best vitelliform macular dystrophy (BVMD and age related macular degeneration (AMD.

  9. RPGR-containing protein complexes in syndromic and non-syndromic retinal degeneration due to ciliary dysfunction

    Indian Academy of Sciences (India)

    Carlos A. Murga-Zamalloa; Anand Swaroop; Hemant Khanna


    Dysfunction of primary cilia due to mutations in cilia-centrosomal proteins is associated with pleiotropic disorders. The primary (or sensory) cilium of photoreceptors mediates polarized trafficking of proteins for efficient phototransduction. Retinitis pigmentosa GTPase regulator (RPGR) is a cilia-centrosomal protein mutated in >70% of X-linked RP cases and 10%–20% of simplex RP males. Accumulating evidence indicates that RPGR may facilitate the orchestration of multiple ciliary protein complexes. Disruption of these complexes due to mutations in component proteins is an underlying cause of associated photoreceptor degeneration. Here, we highlight the recent developments in understanding the mechanism of cilia-dependent photoreceptor degeneration due to mutations in RPGR and RPGR-interacting proteins in severe genetic diseases, including retinitis pigmentosa, Leber congenital amaurosis (LCA), Joubert syndrome, and Senior–Loken syndrome, and explore the physiological relevance of photoreceptor ciliary protein complexes.

  10. Blindness in schoolchildren: importance of heredity, congenital cataract, and prematurity. (United States)

    Phillips, C I; Levy, A M; Newton, M; Stokoe, N L


    Of 99 children in the Royal Blind School, Edinburgh (which serves Scotland and part of N E England), 15 had optic atrophy (hydrocephalus 4, intracranial haemorrhage 2, prematurity 2, fetal distress 2, birth asphyxia 2, cerebral atrophy 1, cardiac arrest during hernia operation 1, and leukaemia 1). Fourteen had congenital cataract, 12 congenital retinal aplasia (Leber's congenital amaurosis) and 11 retinopathy of prematurity. There were small numbers in many other diagnostic categories, including three with non-accidental head injury. Mental retardation, spasticity, and nystagmus were frequent other correlates in all diagnostic categories. 'Very probably hereditary' was a conservative attribution in 36, while 'probable' seemed appropriate for 12-that is, almost 48% were hereditary. Only about 11 cases might have been prevented through genetic counselling, which testifies to the frequency of autosomal recessive hereditary disease, although no parents were consanguineous.

  11. An unusual case of a serious blunt injury of the eye

    Directory of Open Access Journals (Sweden)

    Jovanović Miloš


    Full Text Available Introduction. Optic nerve avulsion is a serious injury of the eye. The objective of the paper was to present the peculiarity of the eye injury caused by a penetrating orbital wound with foreign body being retained in the orbit. Case report. A 15-year-old boy who sustained injury by chain link is presented. While he was turning the chain round in his hand, the last link broke off, piercing the lower lid, penetrated the left orbital cavity and remained behind the eyeball at the top of orbit. While passing towards the top of the orbit, the foreign body caused a blunt injury of the eyeball and avulsion of the ocular nerve. The accurate localization of the foreign body was verified by X-ray and CT imaging. The foreign body was removed through the entry wound. The eye injury resulted in amaurosis. Conclusion. This injury was one of those that could have been prevented.

  12. Primary central nervous system peripheral T-cell lymphoma in a child. (United States)

    Gualco, Gabriela; Wludarski, Sheila; Hayashi-Silva, Luciana; Medeiros Filho, Plinio; Veras, Geni; Bacchi, Carlos Eduardo


    A 10-year-old Caucasian boy was admitted to the hospital with a 3-month history of headache, vomiting, ataxia, and right amaurosis. A magnetic resonance imaging (MRI) showed a solid, expansive, parasagittal mass in the right parietal hemisphere that extended sagitally to include the optical chiasm. The lesion was considered unresectable. Histology and immunophenotyping of biopsy tissue revealed characteristics of peripheral T-cell lymphoma. No other anatomical region, including bone marrow, was compromised. Primary T-cell lymphomas of the central nervous system are rare, especially in childhood. Here, we describe the rapidly deteriorating and fatal clinical course of a boy with a primary T-cell lymphoma in the central nervous system.

  13. Gene-Based Therapies for Leber Hereditary Optic Neuropathy. Hype or Hope? (United States)

    Mackey, David A; Kearns, Lisa S; Hewitt, Alex W


    Leber hereditary optic neuropathy has now joined Leber congenital amaurosis in the list of genetic eye diseases undergoing gene therapy clinical trials. Although a dramatic response to treatment would be welcome, a minor improvement in vision is a major challenge in efficacy assessment, given this may occur spontaneously as part of the natural history of minor recovery in some patients. Thus, we must await the outcome of adequately powered clinical trials to know if the treatment is effective, particularly given the likely high cost of such therapeutic interventions in the future. We need global cooperation to ensure that the most suitable patients are enrolled in these trials and that support is provided for participants who need to travel from the Asia-Pacific region to Europe or North America if there are no local arms of these trials.

  14. [Radiotherapy of choroid metastases in breast carcinoma]. (United States)

    Dobrowsky, W; Schmid, A P; Dobrowsky, E


    From 1975 to 1984, thirteen patients were submitted to radiotherapy for choroid metastases of mammary carcinoma. Bilateral manifestation was found in three cases, thus sixteen eyes have been treated. All irradiations were performed with high voltage equipment. The posterior section of the eye was irradiated with 25 to 50 Gy over 2.5 to 5 weeks. Complete regression was achieved in nine out of sixteen cases, five patients showed an improvement of at least 50%, no considerable effect was found in two cases. The survival is 4 to 48 months (median survival 20 months) from the beginning of radiotherapy. Radiotherapy is a quick, efficient, and sparing treatment in choroid metastases. If applied in due time, it can prevent a visual disorder or amaurosis, thus improving the patients' quality of life.

  15. On the radiotherapy of choroid metastases in mammary carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Dobrowsky, W.; Schmid, A.P.; Dobrowsky, E.


    From 1975 to 1984, thirteen patients were submitted to radiotherapy for choroid metastases of mammary carcinoma. Bilateral manifestation was found in three cases, thus sixteen eyes have been treated. All irradiations were performed with high voltage equipment. The posterior section of the eye was irradiated with 25 to 50 Gy over 2.5 to 5 weeks. Complete regression was achieved in nine out of sixteen cases, five patients showed an improvement of at least 50%, no considerable effect was found in two cases. The survival is 4 to 48 months (median survival 20 months) from the beginning of radiotherapy. Radiotherapy is a quick, efficient, and sparing treatment in choroid metastases. If applied in due time, it can prevent a visual disorder or amaurosis, thus improving the patients' quality of life.

  16. Surgical Management of a Patient with Anterior Megalophthalmos, Lens Subluxation, and a High Risk of Retinal Detachment (United States)

    Esteve, María Carmen Guixeres; Pardo Saiz, Augusto Octavio; Martínez-Costa, Lucía; Dorta, Samuel González-Ocampo; Solana, Pedro Sanz


    The early development of lens opacities and lens subluxation are the most common causes of vision loss in patients with anterior megalophthalmos (AM). Cataract surgery in such patients is challenging, however, because of anatomical abnormalities. Intraocular lens dislocation is the most common postoperative complication. Patients with AM also seem to be affected by a type of vitreoretinopathy that predisposes them to retinal detachment. We here present the case of a 36-year-old man with bilateral AM misdiagnosed as simple megalocornea. He had a history of amaurosis in the right eye due to retinal detachment. He presented with vision loss in the left eye due to lens subluxation. Following the removal of the subluxated lens, it was deemed necessary to perform a vitrectomy in order to prevent retinal detachment. Seven months after surgery, an Artisan® Aphakia iris-claw lens was implanted in the anterior chamber. Fifteen months of follow-up data are provided. PMID:28203198

  17. Revisión bibliográfica sobre la influencia de la baja visión en el estado socioemocional y la calidad de vida de los pacientes mayores



    En esta revisión bibliográfica se objetiva la dificultad de establecer una definición universal para la baja visión a lo largo de la historia. Se puede apreciar cómo los conceptos y definiciones han ido modificándose y evolucionando con el tiempo. Sólo la ceguera total o amaurosis implica ausencia de visión. Pero la mayoría de las personas a las que llamamos comúnmente “ciegas” conservan restos visuales que pueden ser útiles en su vida diaria. Así, entre la ceguera y la visión ...

  18. Transient cortical blindness as a manifestation of solitary cysticercus granuloma. (United States)

    Hussain, Shabbir; Hussain, Kosar; Hussain, Sahar


    Neurocysticercosis is recognised as a significant cause of neurological morbidity in endemic regions. The wide range of pleomorphic and non-specific neurological manifestations of neurocysticercosis must be kept in mind by physicians, as the disease has shown resurgence in developed countries. When an atypical presentation of an unusual tropical disease occurs in non-endemic regions, the diagnosis is often missed. We describe a case of a 4-year-old girl who presented with a history of transient bilateral loss of vision with headache and vomiting. Brain MRI revealed the presence of a single cysticercus granuloma in the occipital lobe. A diagnosis of symptomatic occipital lobe seizure secondary to neurocysticercosis was made. She was given a course of albendazole. There was no recurrence of symptoms at 3 years follow-up. Occipital seizures that are associated with ictal amaurosis closely mimic basilar migraine. Such cases benefit from neuroimaging in order to rule out the underlying structural causes.

  19. Genetics in Ophthalmology III – Posterior Segment Diseases

    Directory of Open Access Journals (Sweden)

    Canan Aslı Utine


    Full Text Available Genetic diseases are congenital or acquired hereditary diseases that result from structural/functional disorders of the human genome. Today, the genetic factors that play a role in many diseases are being highlighted with the rapid progress in the field of genetics science. It becomes increasingly important that physicians from all disciplines have knowledge about the basic principles of genetics, patterns of inheritance, etc., so that they can follow the new developments. In genetic eye diseases, ophthalmologists should know the basic clinical and recently rapidly developing genetic characteristics of these diseases in order to properly approach the diagnosis and treatment and to provide genetic counseling. In this paper, posterior segment eye diseases of genetic origin are reviewed, and retinoblastoma, mitochondrial diseases, retinal dysplasia, retinitis pigmentosa, choroideremia, gyrate atrophy, Alström disease, ocular albinism, optic nerve hypoplasia, anophthalmia/microphthalmia and Leber’s congenital amaurosis are covered. (Turk J Ophthalmol 2012; 42: 386-92

  20. [Extrapontine osmotic myelinolysis]. (United States)

    Silva, Federico A; Rueda-Clausen, Christian F; Ramírez, Fabián


    Extrapontine osmotic myelinolysis is a rare nervous system complication. Symptoms of this malady were presented during the clinical examination of a 49-year-old alcoholic male, who arrived at the hospital emergency room in a state of cardiorespiratory arrest. After resuscitation methods were applied, the patient was found in metabolic acidosis (pH 7.014) and was treated with sodium bicarbonate. Forty-eight hours later, sodium levels in the patient had risen from 142 to 174 mEq/l. During the period of clinical observation, the patient showed signs of cognitive impairment, disartria, bilateral amaurosis, hyporeflexia and right-half body hemiparesias. After 72 hours, computer tomography was applied; this showed a bilateral lenticular hypodensity with internal and external capsule compromise. One month later, when the patient was referred to another institution for rehabilitation, the patient showed cognitive impairment, bilateral optic atrophy, residual disartria, bradikynesia and double hemiparesia.

  1. CRB1: one gene, many phenotypes. (United States)

    Ehrenberg, Miriam; Pierce, Eric A; Cox, Gerald F; Fulton, Anne B


    Mutations in the CRB1 gene cause severe retinal degenerations, which may present as Leber congenital amaurosis, early onset retinal dystrophy, retinitis pigmentosa, or cone-rod dystrophy. Some clinical features should alert the ophthalmologist to the possibility of CRB1 disease. These features are nummular pigmentation of the retina, atrophic macula, retinal degeneration associated with Coats disease, and a unique form of retinitis pigmentosa named para-arteriolar preservation of the retinal pigment epithelium (PPRPE). Retinal degenerations associated with nanophthalmos and hyperopia, or with keratoconus, can serve as further clinical cues to mutations in CRB1. Despite this, no clear genotype-phenotype relationship has been established in CRB1 disease. In CRB1-disease, as in other inherited retinal degenerations (IRDs), it is essential to diagnose the specific disease-causing gene for the disease as genetic therapy has progressed considerably in the last few years and might be applicable.

  2. Adeno-Associated Virus-Mediated Gene Transfer to Renal Tubule Cells via a Retrograde Ureteral Approach

    Directory of Open Access Journals (Sweden)

    Daniel C. Chung


    Full Text Available Background/Aims: Gene therapy involves delivery of exogenous DNA to provide a therapeutic protein. Ideally, a gene therapy vector should be non-toxic, non-immunogenic, easy to produce, and efficient in protecting and delivering DNA into target cells. Methods: Adeno-associated virus (AAV offers these advantages and few, if any, disadvantages, and over 100 isolates exist. We previously showed that AAV-mediated gene therapy can be used to restore vision to patients with Leber’s congenital amaurosis, a disease of childhood blindness. Results: Here we show that novel recombinant AAV2/8 and AAV2/9 transduce kidney tubule cells with high efficiency both in vitroin cell culture and in vivoin mice. In addition, we adapted and modified a retrograde approach to allow for optimal transgene delivery to renal tubular cells that further minimizes the risk of an immunogenic reaction. Conclusions: We believe that recombinant AAV2, especially AAV2/8, gene delivery to renal tubule cells via a retrograde approach represents a viable method for gene therapy for a multitude of renal disorders ranging from autosomal dominant polycystic kidney disease to acute kidney injury.

  3. Transcript annotation prioritization and screening system (TrAPSS) for mutation screening. (United States)

    O'Leary, Brian M; Davis, Steven G; Smith, Michael F; Brown, Bartley; Kemp, Mathew B; Almabrazi, Hakeem; Grundstad, Jason A; Burns, Thomas; Leontiev, Vladimir; Andorf, Jeaneen; Clark, Abbot F; Sheffield, Val C; Casavant, Thomas L; Scheetz, Todd E; Stone, Edwin M; Braun, Terry A


    When searching for disease-causing mutations with polymerase chain reaction (PCR)-based methods, candidate genes are usually screened in their entirety, exon by exon. Genomic resources (i.e.,, and largely support this paradigm for mutation screening by making it easy to view and access sequence data associated with genes in their genomic context. However, the administrative burden of conducting mutation screening in potentially hundreds of genes and thousands of exons in thousands of patients is significant, even with the use of public genome resources. For example, the manual design of oligonucleotide primers for all exons of the 10 Leber's congenital amaurosis (LCA) genes (149 exons) represents a significant information management challenge. The Transcript Annotation Prioritization and Screening System (TrAPSS) is designed to accelerate mutation screening by (1) providing a gene-based local cache of candidate disease genes in a genomic context, (2) automating tasks associated with optimizing candidate disease gene screening and information management, and (3) providing the implementation of an algorithmic technique to utilize large amounts of heterogeneous genome annotation (e.g. conserved protein functional domains) so as to prioritize candidate genes.

  4. [Genetic diagnostic testing in inherited retinal dystrophies]. (United States)

    Kohl, S; Biskup, S


    Inherited retinal dystrophies are clinically and genetically highly heterogeneous. They can be divided according to the clinical phenotype and course of the disease, as well as the underlying mode of inheritance. Isolated retinal dystrophies (i.e., retinitis pigmentosa, Leber's congenital amaurosis, cone and cone-rod dystrophy, macular dystrophy, achromatopsia, congenital stationary nightblindness) and syndromal forms (i.e., Usher syndrome, Bardet-Biedl syndrome) can be differentiated. To date almost 180 genes and thousands of distinct mutations have been identified that are responsible for the different forms of these blinding illnesses. Until recently, there was no adequate diagnostic genetic testing available. With the development of the next generation sequencing technologies, a comprehensive genetic screening analysis for all known genes for inherited retinal dystrophies has been established at reasonable costs and in appropriate turn-around times. Depending on the primary clinical diagnosis and the presumed mode of inheritance, different diagnostic panels can be chosen for genetic testing. Statistics show that in 55-80 % of the cases the genetic defect of the inherited retinal dystrophy can be identified with this approach, depending on the initial clinical diagnosis. The aim of any genetic diagnostics is to define the genetic cause of a given illness within the affected patient and family and thereby i) confirm the clinical diagnosis, ii) provide targeted genetic testing in family members, iii) enable therapeutic intervention, iv) give a prognosis on disease course and progression and v) in the long run provide the basis for novel therapeutic approaches and personalised medicine.

  5. Involvement of Endoplasmic Reticulum Stress in TULP1 Induced Retinal Degeneration.

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    Glenn P Lobo

    Full Text Available Inherited retinal disorders (IRDs result in severe visual impairments in children and adults. A challenge in the field of retinal degenerations is identifying mechanisms of photoreceptor cell death related to specific genetic mutations. Mutations in the gene TULP1 have been associated with two forms of IRDs, early-onset retinitis pigmentosa (RP and Leber congenital amaurosis (LCA. TULP1 is a cytoplasmic, membrane-associated protein shown to be involved in transportation of newly synthesized proteins destined for the outer segment compartment of photoreceptor cells; however, how mutant TULP1 causes cell death is not understood. In this study, we provide evidence that common missense mutations in TULP1 express as misfolded protein products that accumulate within the endoplasmic reticulum (ER causing prolonged ER stress. In an effort to maintain protein homeostasis, photoreceptor cells then activate the unfolded protein response (UPR complex. Our results indicate that the two major apoptotic arms of the UPR pathway, PERK and IRE1, are activated. Additionally, we show that retinas expressing mutant TULP1 significantly upregulate the expression of CHOP, a UPR signaling protein promoting apoptosis, and undergo photoreceptor cell death. Our study demonstrates that the ER-UPR, a known mechanism of apoptosis secondary to an overwhelming accumulation of misfolded protein, is involved in photoreceptor degeneration caused by missense mutations in TULP1. These observations suggest that modulating the UPR pathways might be a strategy for therapeutic intervention.

  6. Bilateral posterior RION after concomitant radiochemotherapy with temozolomide in a patient with glioblastoma multiforme: a case report

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    Gademann Guenther


    Full Text Available Abstract Background Radiation induced optic neuropathy (RION is a rare but severe consequence of radiation therapy that is associated with adjuvant chemotherapy, specifically therapy with vincristine or nitrosoureas. However, there is very little evidence regarding the occurrence of RION after concomitant radiochemotherapy with temozolomide. Case Presentation The case of a 63 year old woman with glioblastoma multiforme and concomitant radiochemotherapy with temozolomide is described. Due to a slight depressive episode the patient also took hypericum perforatum. Five months after cessation of fractionated radiation and adjuvant chemotherapy with temozolomide (cumulative dose of 11040 mg the patient developed bilateral amaurosis due to RION. Tumor regrowth was excluded by magnetic resonance imaging. After the application of gadolinium a pathognomonic contrast enhancement of both prechiasmatic optic nerves could be observed. Conclusions In this patient, the occurrence of RION may have been the result of radiosensitization by temozolomide, which could have been strengthened by hypericin. Consequently, physicians should avoid a concomitant application of hypericum perforatum and radiochemotherapy.

  7. Novel mutations in two Saudi patients with congenital retinal dystrophy

    Directory of Open Access Journals (Sweden)

    Leen Abu Safieh


    Full Text Available To report novel mutations in two Saudi children with clinical features of Leber congenital amaurosis (LCA and Alström syndrome. Case reports. Case 1 was a child with phenotypic features of LCA including oculodigital sign, bilateral enophthalmos, nystagmus, pale disc, and retinal changes. Direct sequencing of the coding sequence of GUCY2D revealed a missense mutation affecting highly conserved position (c. 743C > T; p.S248 L. Case 2 describes a girl with marked nystagmus, photophobia, and retinal changes in both eyes with short and stubby fingers tapering at the distal phalanges. The electroretinograms were nonrecordable in each eye. She had a hearing aid in the left ear, mid-facial hypoplasia, bilateral enophthalmos, and insulin dependent diabetes. Mutation screening of candidates genes revealed a pathogenic mutation in ALMS1 gene (c. 8441C > A, p.S2814*. Two novel mutations causing phenotypic LCA and Alström syndrome in Saudi patients from consanguineous families expand the genotypic spectrum of congenital retinal dystrophies

  8. Efficiency of using rituximab in a patient with generalized granulomatosis with polyangiitis: A case report

    Directory of Open Access Journals (Sweden)

    Gulazyk Malikovna Koilubaeva


    Full Text Available Systemic vasculitides (SVs are characterized by inflammation of the blood vessels wall; the spectrum of their clinical manifestations depends on the type, extent, and location of affected vessels and the activity of systemic inflammation. The etiology of most primary SVs is unknown. Antineutrophil cytoplasmic antibodies (ANCAs are implicated in its pathogenesis. The presence of ANCAa in patients' serum and the correlation of their level with the severity of clinical manifestations served as a basis for identifying a subgroup of systemic necrotizing vasculitides associated with ANCA synthesis: granulomatosis with polyangiitis (GPA, microscopic polyangiitis, and Churg – Strauss syndrome. GPA is characterized by systemic granulomatous necrotizing vasculitis involving the small vessels of the upper respiratory tract, lung, and kidney.The paper describes a case of difficult diagnosis and successful rituximab (RTM treatment of generalized GPA in a 45-year-old female patients. The disease occurred with local damage to the upper respiratory tract, granulomatous inflammation of the pulmonary vessels to form multiple infiltrates with lung tissue destruction elements and necrotizing glomerulonephritis. Despite intensive immunosuppressive treatment, there was a rapid GPA progression with the further development of respiratory failure, which had been induced by stenotic laryngitis subglottica leading to tracheostoma. Damage to the organ of vision could lead to severe complications, including amaurosis. RMT was shown to be effective in treating generalized GPA with a poor prognosis.

  9. A gene for autosomal dominant progressive cone dystrophy (CORD5) maps to chromosome 17p12-p13

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    Balciuniene, J.; Holmgren, G.; Forsman, K. [University Hospital, Umea (Sweden)] [and others


    Inherited retinal dystrophy is a common cause of visual impairment. Cone dystrophy affects the cone function and is manifested as progressive loss of the central vision, defective color vision, and photophobia. Linkage was demonstrated between progressive cone dystrophy (CORD5) and genetic markers on chromosome 17p12-p13 in a five-generation family. Multipoint analysis gave a maximum lod score of 7.72 at the marker D17S938. Recombinant haplotypes in the family suggest that the cone dystrophy locus is located in a 25-cM interval between the markers D17S926/D17S849 and D17S804/D17S945. Furthermore, one recombination was detected between the disease locus and a microsatellite marker in the candidate gene RCV1, encoding the retinal protein recoverin. Two additional candidate genes encoding retinal guanylate cyclase (GUC2D) and pigment epithelium-derived factor (PEDF) are located at 17p13.1. Moreover, loci for retinitis pigmentosa and Leber congenital amaurosis have been mapped to the same region. Identification of the cone dystrophy locus may be of importance not only for identifying functional genes in the cone system, but also for identifying genes for other retinal disorders. 34 refs., 3 figs., 2 tabs.

  10. S/MAR-containing DNA nanoparticles promote persistent RPE gene expression and improvement in RPE65-associated LCA. (United States)

    Koirala, Adarsha; Makkia, Rasha S; Conley, Shannon M; Cooper, Mark J; Naash, Muna I


    Mutations in genes in the retinal pigment epithelium (RPE) cause or contribute to debilitating ocular diseases, including Leber's congenital amaurosis (LCA). Genetic therapies, particularly adeno-associated viruses (AAVs), are a popular choice for monogenic diseases; however, the limited payload capacity of AAVs combined with the large number of retinal disease genes exceeding that capacity make the development of alternative delivery methods critical. Here, we test the ability of compacted DNA nanoparticles (NPs) containing a plasmid with a scaffold matrix attachment region (S/MAR) and vitelliform macular dystrophy 2 (VMD2) promoter to target the RPE, drive long-term, tissue-specific gene expression and mediate proof-of-principle rescue in the rpe65(-/-) model of LCA. We show that the S/MAR-containing plasmid exhibited reporter gene expression levels several fold higher than plasmid or NPs without S/MARs. Importantly, this expression was highly persistent, lasting up to 2 years (last timepoint studied). We therefore selected this plasmid for testing in the rpe65(-/-) mouse model and observe that NP or plasmid VMD2-hRPE65-S/MAR led to structural and functional improvements in the LCA disease phenotype. These results indicate that the non-viral delivery of hRPE65 vectors can result in persistent, therapeutically efficacious gene expression in the RPE.

  11. In vitro and in vivo rescue of aberrant splicing in CEP290-associated LCA by antisense oligonucleotide delivery. (United States)

    Garanto, Alejandro; Chung, Daniel C; Duijkers, Lonneke; Corral-Serrano, Julio C; Messchaert, Muriël; Xiao, Ru; Bennett, Jean; Vandenberghe, Luk H; Collin, Rob W J


    Leber congenital amaurosis (LCA) is a severe disorder resulting in visual impairment usually starting in the first year of life. The most frequent genetic cause of LCA is an intronic mutation in CEP290 (c.2991 + 1655A > G) that creates a cryptic splice donor site resulting in the insertion of a pseudoexon (exon X) into CEP290 mRNA. Previously, we showed that naked antisense oligonucleotides (AONs) effectively restored normal CEP290 splicing in patient-derived lymphoblastoid cells. We here explore the therapeutic potential of naked and adeno-associated virus (AAV)-packaged AONs in vitro and in vivo In both cases, AON delivery fully restored CEP290 pre-mRNA splicing, significantly increased CEP290 protein levels and rescued a ciliary phenotype present in patient-derived fibroblast cells. Moreover, administration of naked and AAV-packaged AONs to the retina of a humanized mutant Cep290 mouse model, carrying the intronic mutation, showed a statistically significant reduction of exon X-containing Cep290 transcripts, without compromising the retinal structure. Together, our data highlight the tremendous therapeutic prospective of AONs for the treatment of not only CEP290-associated LCA but potentially many other subtypes of retinal dystrophy caused by splicing mutations.

  12. The inherited blindness protein AIPL1 regulates the ubiquitin-like FAT10 pathway.

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    John S Bett

    Full Text Available Mutations in AIPL1 cause the inherited blindness Leber congenital amaurosis (LCA. AIPL1 has previously been shown to interact with NUB1, which facilitates the proteasomal degradation of proteins modified with the ubiquitin-like protein FAT10. Here we report that AIPL1 binds non-covalently to free FAT10 and FAT10ylated proteins and can form a ternary complex with FAT10 and NUB1. In addition, AIPL1 antagonised the NUB1-mediated degradation of the model FAT10 conjugate, FAT10-DHFR, and pathogenic mutations of AIPL1 were defective in inhibiting this degradation. While all AIPL1 mutants tested still bound FAT10-DHFR, there was a close correlation between the ability of the mutants to interact with NUB1 and their ability to prevent NUB1-mediated degradation. Interestingly, AIPL1 also co-immunoprecipitated the E1 activating enzyme for FAT10, UBA6, suggesting AIPL1 may have a role in directly regulating the FAT10 conjugation machinery. These studies are the first to implicate FAT10 in retinal cell biology and LCA pathogenesis, and reveal a new role of AIPL1 in regulating the FAT10 pathway.

  13. Genetic screening of LCA in Belgium: predominance of CEP290 and identification of potential modifier alleles in AHI1 of CEP290-related phenotypes. (United States)

    Coppieters, Frauke; Casteels, Ingele; Meire, Françoise; De Jaegere, Sarah; Hooghe, Sally; van Regemorter, Nicole; Van Esch, Hilde; Matuleviciene, Ausra; Nunes, Luis; Meersschaut, Valérie; Walraedt, Sophie; Standaert, Lieve; Coucke, Paul; Hoeben, Heidi; Kroes, Hester Y; Vande Walle, Johan; de Ravel, Thomy; Leroy, Bart P; De Baere, Elfride


    Leber Congenital Amaurosis (LCA), the most severe inherited retinal dystrophy, is genetically heterogeneous, with 14 genes accounting for 70% of patients. Here, 91 LCA probands underwent LCA chip analysis and subsequent sequencing of 6 genes (CEP290, CRB1, RPE65, GUCY2D, AIPL1and CRX), revealing mutations in 69% of the cohort, with major involvement of CEP290 (30%). In addition, 11 patients with early-onset retinal dystrophy (EORD) and 13 patients with Senior-Loken syndrome (SLS), LCA-Joubert syndrome (LCA-JS) or cerebello-oculo-renal syndrome (CORS) were included. Exhaustive re-inspection of the overall phenotypes in our LCA cohort revealed novel insights mainly regarding the CEP290-related phenotype. The AHI1 gene was screened as a candidate modifier gene in three patients with the same CEP290 genotype but different neurological involvement. Interestingly, a heterozygous novel AHI1 mutation, p.Asn811Lys, was found in the most severely affected patient. Moreover, AHI1 screening in five other patients with CEP290-related disease and neurological involvement revealed a second novel missense variant, p.His758Pro, in one LCA patient with mild mental retardation and autism. These two AHI1 mutations might thus represent neurological modifiers of CEP290-related disease.

  14. C2 Domains as Protein-Protein Interaction Modules in the Ciliary Transition Zone

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    Kim Remans


    Full Text Available RPGR-interacting protein 1 (RPGRIP1 is mutated in the eye disease Leber congenital amaurosis (LCA and its structural homolog, RPGRIP1-like (RPGRIP1L, is mutated in many different ciliopathies. Both are multidomain proteins that are predicted to interact with retinitis pigmentosa G-protein regulator (RPGR. RPGR is mutated in X-linked retinitis pigmentosa and is located in photoreceptors and primary cilia. We solved the crystal structure of the complex between the RPGR-interacting domain (RID of RPGRIP1 and RPGR and demonstrate that RPGRIP1L binds to RPGR similarly. RPGRIP1 binding to RPGR affects the interaction with PDEδ, the cargo shuttling factor for prenylated ciliary proteins. RPGRIP1-RID is a C2 domain with a canonical β sandwich structure that does not bind Ca2+ and/or phospholipids and thus constitutes a unique type of protein-protein interaction module. Judging from the large number of C2 domains in most of the ciliary transition zone proteins identified thus far, the structure presented here seems to constitute a cilia-specific module that is present in multiprotein transition zone complexes.

  15. Hidden Genetic Variation in LCA9-Associated Congenital Blindness Explained by 5'UTR Mutations and Copy-Number Variations of NMNAT1. (United States)

    Coppieters, Frauke; Todeschini, Anne Laure; Fujimaki, Takuro; Baert, Annelot; De Bruyne, Marieke; Van Cauwenbergh, Caroline; Verdin, Hannah; Bauwens, Miriam; Ongenaert, Maté; Kondo, Mineo; Meire, Françoise; Murakami, Akira; Veitia, Reiner A; Leroy, Bart P; De Baere, Elfride


    Leber congenital amaurosis (LCA) is a severe autosomal-recessive retinal dystrophy leading to congenital blindness. A recently identified LCA gene is NMNAT1, located in the LCA9 locus. Although most mutations in blindness genes are coding variations, there is accumulating evidence for hidden noncoding defects or structural variations (SVs). The starting point of this study was an LCA9-associated consanguineous family in which no coding mutations were found in the LCA9 region. Exploring the untranslated regions of NMNAT1 revealed a novel homozygous 5'UTR variant, c.-70A>T. Moreover, an adjacent 5'UTR variant, c.-69C>T, was identified in a second consanguineous family displaying a similar phenotype. Both 5'UTR variants resulted in decreased NMNAT1 mRNA abundance in patients' lymphocytes, and caused decreased luciferase activity in human retinal pigment epithelial RPE-1 cells. Second, we unraveled pseudohomozygosity of a coding NMNAT1 mutation in two unrelated LCA patients by the identification of two distinct heterozygous partial NMNAT1 deletions. Molecular characterization of the breakpoint junctions revealed a complex Alu-rich genomic architecture. Our study uncovered hidden genetic variation in NMNAT1-associated LCA and emphasized a shift from coding to noncoding regulatory mutations and repeat-mediated SVs in the molecular pathogenesis of heterogeneous recessive disorders such as hereditary blindness.

  16. Concise Review: Patient-Specific Stem Cells to Interrogate Inherited Eye Disease. (United States)

    Giacalone, Joseph C; Wiley, Luke A; Burnight, Erin R; Songstad, Allison E; Mullins, Robert F; Stone, Edwin M; Tucker, Budd A


    Whether we are driving to work or spending time with loved ones, we depend on our sense of vision to interact with the world around us. Therefore, it is understandable why blindness for many is feared above death itself. Heritable diseases of the retina, such as glaucoma, age-related macular degeneration, and retinitis pigmentosa, are major causes of blindness worldwide. The recent success of gene augmentation trials for the treatment of RPE65-associated Leber congenital amaurosis has underscored the need for model systems that accurately recapitulate disease. With the advent of patient-specific induced pluripotent stem cells (iPSCs), researchers are now able to obtain disease-specific cell types that would otherwise be unavailable for molecular analysis. In the present review, we discuss how the iPSC technology is being used to confirm the pathogenesis of novel genetic variants, interrogate the pathophysiology of disease, and accelerate the development of patient-centered treatments. Significance: Stem cell technology has created the opportunity to advance treatments for multiple forms of blindness. Researchers are now able to use a person's cells to generate tissues found in the eye. This technology can be used to elucidate the genetic causes of disease and develop treatment strategies. In the present review, how stem cell technology is being used to interrogate the pathophysiology of eye disease and accelerate the development of patient-centered treatments is discussed.


    Directory of Open Access Journals (Sweden)

    Skrijelj Fadil E


    Full Text Available Introduction: Occipital lobe epilepsies are rarely met in clinical practice, but when they occur, they can be misdiagnosed as migraine-like headache. Their prevalence ranges from 5%to 10% of all epilepsies. Seizures can occur at any age; etiologically speaking they can be symptomatic, cryptogenic and idiopathic (most often onsetis in childhood. Clinical symptomatology is manifested by partial epileptic seizures in the sense of visual elementary and/or complex manifestations, palinopsia, amaurosis, tonic head deviation, bulbus, nistagmus and headache. Propagation discharge to neighbour areas (temporal, parietal and frontal is a frequent occurrence appearing with complex partial seizures frequently finishing with secondary generalized tonic-clonic (GTC seizures. Case report: We are presenting a17-year-old male patient who has suffered from attacks of visual problemswith headache since 10 years of age. All the time it is treated as a migraine headache. During the last attack of headache the patient also had a loss of consciousness, EEG that was performed for the first time evidenced epileptic discharges of the occipital area. The therapy also included treatment with antiepileptic drug pregabalin resulting in seizure withdrawal. Conclusion: The appearance of visual symptoms followed by headache is most frequently qualified as migraine triggered headache. However, when antimigraine therapy does not give favorable results epileptic headache should be suspected, with obligatory performance of EEG recording. Occipital lobe epilepsy often presents diagnostic dilemmas due to clinical manifestations that are similar to that of non-migraine headache.

  18. RPE65 gene: multiplex PCR and mutation screening in patients from India with retinal degenerative diseases

    Indian Academy of Sciences (India)

    Biju Joseph; Anuradha Srinivasan; Nagasamy Soumittra; Authiappan Vidhya; Nitin Shridhara Shetty; Satagopan Uthra; Govindasamy Kumaramanickavel


    We used multiplex PCR followed by sequencing to screen for mutations in the 14 exons of the RPE65 gene in early-childhood-onset autosomal recessive retinitis pigmentosa (arRP) and Leber’s congenital amaurosis (LCA) patients. The RPE65 protein is believed to play an important role in the metabolism of vitamin A in the visual cycle and mutations identified in the gene could have implications for vitamin A-based therapeutic intervention. We were able to identify a homozygous mutation (AAT → AAG) in exon 9 in an arRP patient and a heterozygous missense transversion (AAT → AAG) also in exon 9 of an LCA patient. We also identified a polymorphism in exon 10 (GAG → GAA) in an arRP as well as an LCA patient. Mutation screening would be greatly facilitated by multiplex PCR which could cut down costs, labour and time involved. The nucleotide changes observed in this study could be de novo. Though a larger study has been undertaken, from the preliminary results it appears that in India the RPE65 gene seems to be less involved in causation of LCA.

  19. Homozygosity mapping and targeted sanger sequencing reveal genetic defects underlying inherited retinal disease in families from pakistan.

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    Maleeha Maria

    Full Text Available Homozygosity mapping has facilitated the identification of the genetic causes underlying inherited diseases, particularly in consanguineous families with multiple affected individuals. This knowledge has also resulted in a mutation dataset that can be used in a cost and time effective manner to screen frequent population-specific genetic variations associated with diseases such as inherited retinal disease (IRD.We genetically screened 13 families from a cohort of 81 Pakistani IRD families diagnosed with Leber congenital amaurosis (LCA, retinitis pigmentosa (RP, congenital stationary night blindness (CSNB, or cone dystrophy (CD. We employed genome-wide single nucleotide polymorphism (SNP array analysis to identify homozygous regions shared by affected individuals and performed Sanger sequencing of IRD-associated genes located in the sizeable homozygous regions. In addition, based on population specific mutation data we performed targeted Sanger sequencing (TSS of frequent variants in AIPL1, CEP290, CRB1, GUCY2D, LCA5, RPGRIP1 and TULP1, in probands from 28 LCA families.Homozygosity mapping and Sanger sequencing of IRD-associated genes revealed the underlying mutations in 10 families. TSS revealed causative variants in three families. In these 13 families four novel mutations were identified in CNGA1, CNGB1, GUCY2D, and RPGRIP1.Homozygosity mapping and TSS revealed the underlying genetic cause in 13 IRD families, which is useful for genetic counseling as well as therapeutic interventions that are likely to become available in the near future.

  20. Asteroid hyalosis--current state of knowledge. (United States)

    Jabłońska, Anna; Ciszewska, Joanna; Kęcik, Dariusz


    The search query into the Cochrane Library, Medline, Web of Science, Embase, Scopus and ScienceDirect enabled selection of research papers addressing the issue of asteroid hyalosis published in English between 1963 and January 2014. Asteroid hyalosis is a degenerative condition of the vitreous in which small, creamy or white, spherical particles (asteroid bodies) are randomly diffused within the vitreous. They consist mainly of calcium and phosphorus and have a structure of hydroxy lapatite. In 80.2-92.0% of cases the condition affects one eye only and it occurs in 0.36-1.96% of population, mostly in patients over 50 years of age and in males. Hypercholesterolemia and hypertension are systemic risk factors, but asteroid hyalosis is postulated to occur more often in retinitis pigmentosa and Leber amaurosis caused by mutations in lecithin retinol acyltransferase gene. Asteroid hyalosis also causes calcification of some intraocular lenses--mostly silicone ones. Vitreous of patients with asteroid hyalosis shows reduced gel liquefaction and anomalous vitreoretinal adhesion.

  1. Vitamin A derivatives as treatment options for retinal degenerative diseases. (United States)

    Perusek, Lindsay; Maeda, Tadao


    The visual cycle is a sequential enzymatic reaction for vitamin A, all-trans-retinol, occurring in the outer layer of the human retina and is essential for the maintenance of vision. The central source of retinol is derived from dietary intake of both retinol and pro-vitamin A carotenoids. A series of enzymatic reactions, located in both the photoreceptor outer segment and the retinal pigment epithelium, transform retinol into the visual chromophore 11-cis-retinal, regenerating visual pigments. Retina specific proteins carry out the majority of the visual cycle, and any significant interruption in this sequence of reactions is capable of causing varying degrees of blindness. Among these important proteins are Lecithin:retinol acyltransferase (LRAT) and retinal pigment epithelium-specific 65-kDa protein (RPE65) known to be responsible for esterification of retinol to all-trans-retinyl esters and isomerization of these esters to 11-cis-retinal, respectively. Deleterious mutations in these genes are identified in human retinal diseases that cause blindness, such as Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP). Herein, we discuss the pathology of 11-cis-retinal deficiency caused by these mutations in both animal disease models and human patients. We also review novel therapeutic strategies employing artificial visual chromophore 9-cis-retinoids which have been employed in clinical trials involving LCA patients.

  2. Vitamin A Derivatives as Treatment Options for Retinal Degenerative Diseases

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    Tadao Maeda


    Full Text Available The visual cycle is a sequential enzymatic reaction for vitamin A, all-trans-retinol, occurring in the outer layer of the human retina and is essential for the maintenance of vision. The central source of retinol is derived from dietary intake of both retinol and pro-vitamin A carotenoids. A series of enzymatic reactions, located in both the photoreceptor outer segment and the retinal pigment epithelium, transform retinol into the visual chromophore 11-cis-retinal, regenerating visual pigments. Retina specific proteins carry out the majority of the visual cycle, and any significant interruption in this sequence of reactions is capable of causing varying degrees of blindness. Among these important proteins are Lecithin:retinol acyltransferase (LRAT and retinal pigment epithelium-specific 65-kDa protein (RPE65 known to be responsible for esterification of retinol to all-trans-retinyl esters and isomerization of these esters to 11-cis-retinal, respectively. Deleterious mutations in these genes are identified in human retinal diseases that cause blindness, such as Leber congenital amaurosis (LCA and retinitis pigmentosa (RP. Herein, we discuss the pathology of 11-cis-retinal deficiency caused by these mutations in both animal disease models and human patients. We also review novel therapeutic strategies employing artificial visual chromophore 9-cis-retinoids which have been employed in clinical trials involving LCA patients.

  3. A role for the extracellular domain of Crumbs in morphogenesis of Drosophila photoreceptor cells. (United States)

    Richard, Mélisande; Muschalik, Nadine; Grawe, Ferdi; Ozüyaman, Susann; Knust, Elisabeth


    Morphogenesis of Drosophila photoreceptor cells includes the subdivision of the apical membrane into the photosensitive rhabdomere and the associated stalk membrane, as well as a considerable elongation of the cell. Drosophila Crumbs (Crb), an evolutionarily conserved transmembrane protein, organizes an apical protein scaffold, which is required for elongation of the photoreceptor cell and extension of the stalk membrane. To further elucidate the role played by different Crb domains during eye morphogenesis, we performed a structure-function analysis in the eye. The analysis showed that the three variants tested, namely full-length Crb, the membrane-bound intracellular domain and the extracellular domain were able to rescue the elongation defects of crb mutant rhabdomeres. However, only full-length Crb and the membrane-bound intracellular domain could partially restore the length of the stalk membrane, while the extracellular domain failed to do so. This failure was associated with the inability of the extracellular domain to recruit beta(Heavy)-spectrin to the stalk membrane. These results highlight the functional importance of the extracellular domain of Crb in the Drosophila eye. They are in line with previous observations, which showed that mutations in the extracellular domain of human CRB1 are associated with retinitis pigmentosa 12 and Leber congenital amaurosis, two severe forms of retinal dystrophy.

  4. [Balloon occlusion test of the internal carotid artery for evaluating resectability of blood vessel infiltrating cervical metastasis of advanced head and neck cancers--Heidelberg experience]. (United States)

    Dietz, A; von Kummer, R; Adams, H P; Kneip, M; Galito, P; Maier, H


    During the last two years 17 patients of the ENT-Department of the University of Heidelberg suffering from squamous-cell carcinomas of the head and neck underwent a balloon occlusion test of the internal carotid artery (ICA). The investigation was performed because of tumorous infiltration of the large cervical vessels. The balloon occlusion of the ICA was accomplished at the Department of Neuroradiology of the University of Heidelberg. While stopping bloodflow in the ICA of one side for 15-20 min, clinical, electrophysiological and Doppler sonographic monitoring was performed, to detect severe cerebral complications. The specific electrophysiological monitoring contained the detection of MSSEP's (median nerve stimulated somatosensorial evoked potentials) and TCMEP's (transcortical motor evoked potentials) during test occlusion. Balloon occlusion was not possible in three patients because of severe arteriosclerosis. Test occlusion had to be discontinued in three patients because of clinical complications (temporary amaurosis, orthostatic complications). Finally, seven patients showed contraindications during test occlusion for permanent occlusion of the ICA. Four patients had a permanent occlusion of the ICA after tumour resection. In two patients the ICA was removed without problems in test occlusion. The third patient underwent a permanent carotid occlusion because of bleeding complications (in spite of poor clinical tolerance of the test occlusion). In the fourth patient, only intraoperative neuromonitoring with MSSEP's was conducted before permanent carotid occlusion. All four patients did not show any neurological deficits after resection of the ICA. Neurophysiological monitoring played an important role in predicting cerebral complications after permanent occlusion of the ICA.

  5. HHV-6 encephalitis in pediatric pazient: case report

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    Agata Calvario


    Full Text Available We report the case of a seventeen-month-old child, with a monocular amaurosis, hospitalized for inconsolable crying followed by a deep sleepiness.At neurological examination, and in the absence of clearly focal neurological signs, the child seemed drowsy and could wake only by moderately intense stimuli.A modest metabolic acidosis and an occasional delay of brain electrical activity at EEG, especially on posterior regions of the right hemisphere, were reported. Cranial CT scan, encephalic NMR and ECG were negative. Standard analysis and isofocusing of cerebro-spinal fluid (CSF were normal, while the virological analysis by Real Time PCR, performed on CSF and whole blood, revealed the presence of HHV-6 DNA. Guthrie Card, tested in triplicate, was positive for HHV-6 and negative for CMV. An antiviral, antibiotic and glucorticoid therapy was started. Following clinical improvement, the little patient was dismissed with a diagnosis of HHV-6 encephalitis. Neurological damages linked to HHV-6 are documented in pediatric patients. But while the infection is suspected of possible vertical viral transmission, HHV-6 remains a little known and misdiagnosed virus.

  6. Synaptogenesis and outer segment formation are perturbed in the neural retina of Crx mutant mice

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    Raviola Elio


    Full Text Available Abstract Background In Leber's congenital amaurosis (LCA, affected individuals are blind, or nearly so, from birth. This early onset suggests abnormal development of the neural retina. Mutations in genes that affect the development and/or function of photoreceptor cells have been found to be responsible in some families. These examples include mutations in the photoreceptor transcription factor, Crx. Results A Crx mutant strain of mice was created to serve as a model for LCA and to provide more insight into Crx's function. In this study, an ultrastructural analysis of the developing retina in Crx mutant mice was performed. Outer segment morphogenesis was found to be blocked at the elongation stage, leading to a failure in production of the phototransduction apparatus. Further, Crx-/- photoreceptors demonstrated severely abnormal synaptic endings in the outer plexiform layer. Conclusions This is the first report of a synaptogenesis defect in an animal model for LCA. These data confirm the essential role this gene plays in multiple aspects of photoreceptor development and extend our understanding of the basic pathology of LCA.

  7. [A case of akin moyamoya disease associated with type-I diabetes mellitus managed by extracranial-intracranial bypass]. (United States)

    Akamatsu, Yosuke; Fujimura, Miki; Sakata, Hiroyuki; Endo, Hidenori; Itabashi, Ryo; Tominaga, Teiji


    Moyamoya disease is characterized by idiopathic steno-occlusion at the terminal portion of the internal carotid artery with concomitant abnormal vascular networks that can lead to transient ischemic attacks and hemorrhagic stroke with symptoms of headache, confusion, dizziness, ataxia, seizure, and cognitive and personality changes. Because these symptoms also occur in patients with type 1 diabetes mellitus(T1DM), patients with both diseases might go unnoticed and without the less common diagnosis of akin moyamoya disease, accurate diagnosis and treatment could be delayed. Here, we report the case of a 32-year-old woman with past history of T1DM for 26 years presenting with right amaurosis, which was diagnosed as akin moyamoya disease even though she had suffered right incomplete hemiparesis 2 years ago. She underwent superficial temporal artery-middle cerebral artery anastomosis with pial synangiosis in the left hemisphere without complication. She had no cerebrovascular events postoperatively. Although akin moyamoya disease associated with T1DM is rare in Japan, we recommend that clinicians consider the coexistence of both diseases when evaluating patients with T1DM who have neurologic signs or symptoms and not overlook the possibility of cerebrovascular diseases, such as akin moyamoya disease.


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    Nenad GLUMBIC


    Full Text Available Autoagressive behavior is a relatively frequent symptom of mental disturbances and behavior disturbances which are the subject of professional engagement of clinically oriented defectologists. In the process of rehabilitation numerous methods are used, from behavioral to psychopharmacological ones by which the above mentioned problems are eliminated of softened.The paper deals with four children with different diagnosis (autism, disintegrative psychosis, Patau syndrome and amaurosis that have the same common denominator-mental retardation and autoagression.We have tried to point out-by the description of a study case as well as the ways od work with these children-an application possibly of the particular methods of general and special re-education of psychomotorics in the process of autoagressive ways of behavior minimizing.The paper gives the autor’s notion of indications for re-educative method application with in the multihandicapped children population. Defectological treatment discovers new forms of existence in the existential field, not only to the retarded child but also to the very therapist. Epistemological consequences of the mentioned transfer are given in details in the paper.

  9. 心房颤动伴长RR间期的食管电生理研究%Esophagus electrophysiological test in atrial fibrillation associated with long RR interval

    Institute of Scientific and Technical Information of China (English)



    Objective To improve awareness and diagnostic level of atrial fibrillation associated with long RR interval. Methods A clinical data of 22 cases of atrial fibrillation associated with long RR interval were analyzed retrospectively. Results Ninteen cases occurred in night or sleep without obvious symptom, 3 cases all occurred after a day of activity accompanied by dizzyamaurosis fugax and swoon. Sinoatrial node and atrioventricular node function of 19 cases were normal after electrical conversion in esophagus eleetrophysiological test. One ease was diagnosed sick sinus syndrome and 2 cases were diagnosed high grade A - V block, these 3 cases all received pacemaker implantation. Conclusions The mechanism of atrial fibrillation associated with long RR interval is complex whether sick sinus syndrome existing or pathological atrioventricular block are allowed to determine by hoher combined symptom.%目的 提高对心房颤动伴长RR间期的认识及诊断水平.方法 回顾性分析我院22例心房颤动伴长RR间期患者的临床资料.结果 19例长RR间期发生于夜间或睡眠时,患者无明显症状;3例伴有头晕、一过性黑朦、晕厥的患者均发生在白天活动后.电复律后食管电生理检查,19例房室结功能正常,1例诊断为病态窦房结综合征,2例诊断为高度房室传导阻滞,3例患者安装永久起搏器.结论 心房颤动伴长RR间期的机制较复杂,动态心电图和症状结合有助于判断是否存在病理性房室传导阻滞或病态窦房结综合征.

  10. The soil seed bank characteristics in cropland under different conservation tillage and fertilization regimes in Loess Hill and Gully Region%陕北黄土丘陵沟壑区水土保持耕作及施肥下农田土壤种子库特征

    Institute of Scientific and Technical Information of China (English)

    黄茂林; 梁银丽; 周茂娟; 韦泽秀; 吴燕


    To better understand the mechanism of weed occurrence and suppression effect of crops on weeds, we conducted a 4-year field experiment in 4 crops under different tillage and fertilization regimes in Ansai, Shaanxi, China. The species composition, seed density, diversity and the similarity were measured in soil seed bank of soybean (Glycine max), corn (Zea mays), Red Bean (Semen Phaseoli ) and potato (Solanum tuberosum). The tillage and fertilization treatments in each crop included till-chemical fertilizer (CF), till-organic manure (CM), till no fertilizer (CN), no-till chemical fertilizer (NF), no-till-organic manure (NM), and no-till-no fertilizer (NN). The results showed that: (1) There were 12 weed species in 1965 seedlings from 24 soil samples in 4 crops. These species belonged to 7 families and 12 genuses and 94% of them were annual weeds. Bangtou grass (fugax nees ex steud), amaranth (Acalypha australis), large crabgrass (Digitaria sanguinalis) and Poa(Poa sphondylodes)were the dominant species and accounted for 87%;(2) In 0-20cm soil of different treatments, weed density ranged from (282.9 ± 63) to (7482.5 ±1078.3) seeds · m-2. There were significant differences (P potato plot > soybean plot > corn plot among 4 crops, tillage plot > no-tillage plot between 2 tillage treatments, and organic fertilizer plot > Fertilizer plot > no fertilizer plot among fertilization treatments;(3) Soil seed bank had the highest weed density in NM Red Bean and the lowest density in NN corn. The rich index was the highest (2.30) in CF soybean and the lowest (0.29) in NN Red Bean. The diversity index was the highest in NN soybean (5.56) and the lowest in CF Red bean (0.45). The ecological advantage of NF corn was the highest (1.35) and that of CF soybean was the lowest (0.17). Among the fertilization treatments, the similar coefficient of soil seed bank ranged from 0 to 0.63 in tilled system and from 0.67 to 0.92 in no-till system. As a result, corn and soybean were optimal

  11. Premature Truncation of a Novel Protein, RD3, Exhibiting Subnuclear Localization Is Associated with Retinal Degeneration (United States)

    Friedman, James S. ; Chang, Bo ; Kannabiran, Chitra ; Chakarova, Christina ; Singh, Hardeep P. ; Jalali, Subhadra ; Hawes, Norman L. ; Branham, Kari ; Othman, Mohammad ; Filippova, Elena ; Thompson, Debra A. ; Webster, Andrew R. ; Andréasson, Sten ; Jacobson, Samuel G. ; Bhattacharya, Shomi S. ; Heckenlively, John R. ; Swaroop, Anand 


    The rd3 mouse is one of the oldest identified models of early-onset retinal degeneration. Using the positional candidate approach, we have identified a C→T substitution in a novel gene, Rd3, that encodes an evolutionarily conserved protein of 195 amino acids. The rd3 mutation results in a predicted stop codon after residue 106. This change is observed in four rd3 lines derived from the original collected mice but not in the nine wild-type mouse strains that were examined. Rd3 is preferentially expressed in the retina and exhibits increasing expression through early postnatal development. In transiently transfected COS-1 cells, the RD3-fusion protein shows subnuclear localization adjacent to promyelocytic leukemia-gene-product bodies. The truncated mutant RD3 protein is detectable in COS-1 cells but appears to get degraded rapidly. To explore potential association of the human RD3 gene at chromosome 1q32 with retinopathies, we performed a mutation screen of 881 probands from North America, India, and Europe. In addition to several alterations of uncertain significance, we identified a homozygous alteration in the invariant G nucleotide of the RD3 exon 2 donor splice site in two siblings with Leber congenital amaurosis. This mutation is predicted to result in premature truncation of the RD3 protein, segregates with the disease, and is not detected in 121 ethnically matched control individuals. We suggest that the retinopathy-associated RD3 protein is part of subnuclear protein complexes involved in diverse processes, such as transcription and splicing. PMID:17186464

  12. Lecithin:Retinol Acyltransferase: A Key Enzyme Involved in the Retinoid (visual) Cycle. (United States)

    Sears, Avery E; Palczewski, Krzysztof


    Lecithin:retinol acyltransferase (LRAT) catalyzes the acyl transfer from the sn-1 position of phosphatidylcholine (PC) to all-trans-retinol, creating fatty acid retinyl esters (palmitoyl, stearoyl, and some unsaturated derivatives). In the eye, these retinyl esters are substrates for the 65 kDa retinoid isomerase (RPE65). LRAT is well characterized biochemically, and recent structural data from closely related family members of the NlpC/P60 superfamily and a chimeric protein have established its catalytic mechanism. Mutations in the LRAT gene are responsible for approximately 1% of reported cases of Leber congenital amaurosis (LCA). Lack of functional LRAT, expressed in the retinal pigmented epithelium (RPE), results in loss of the visual chromophore and photoreceptor degeneration. LCA is a rare hereditary retinal dystrophy with an early onset associated with mutations in one of 21 known genes. Protocols have been devised to identify therapeutics that compensate for mutations in RPE65, also associated with LCA. The same protocols can be adapted to combat dystrophies associated with LRAT. Improvement in the visual function of clinical recipients of therapy with recombinant adeno-associated virus (rAAV) vectors incorporating the RPE65 gene provides a proof of concept for LRAT, which functions in the same cell type and metabolic pathway as RPE65. In parallel, a clinical trial that employs oral 9-cis-retinyl acetate to replace the missing chromophore in RPE65 and LRAT causative disease has proven to be effective and free of adverse effects. This article summarizes the biochemistry of LRAT and examines chromophore replacement as a treatment for LCA caused by LRAT mutations.

  13. Lentiviral expression of retinal guanylate cyclase-1 (RetGC1 restores vision in an avian model of childhood blindness.

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    Melissa L Williams


    Full Text Available BACKGROUND: Leber congenital amaurosis (LCA is a genetically heterogeneous group of retinal diseases that cause congenital blindness in infants and children. Mutations in the GUCY2D gene that encodes retinal guanylate cyclase-1 (retGC1 were the first to be linked to this disease group (LCA type 1 [LCA1] and account for 10%-20% of LCA cases. These mutations disrupt synthesis of cGMP in photoreceptor cells, a key second messenger required for function of these cells. The GUCY1*B chicken, which carries a null mutation in the retGC1 gene, is blind at hatching and serves as an animal model for the study of LCA1 pathology and potential treatments in humans. METHODS AND FINDINGS: A lentivirus-based gene transfer vector carrying the GUCY2D gene was developed and injected into early-stage GUCY1*B embryos to determine if photoreceptor function and sight could be restored to these animals. Like human LCA1, the avian disease shows early-onset blindness, but there is a window of opportunity for intervention. In both diseases there is a period of photoreceptor cell dysfunction that precedes retinal degeneration. Of seven treated animals, six exhibited sight as evidenced by robust optokinetic and volitional visual behaviors. Electroretinographic responses, absent in untreated animals, were partially restored in treated animals. Morphological analyses indicated there was slowing of the retinal degeneration. CONCLUSIONS: Blindness associated with loss of function of retGC1 in the GUCY1*B avian model of LCA1 can be reversed using viral vector-mediated gene transfer. Furthermore, this reversal can be achieved by restoring function to a relatively low percentage of retinal photoreceptors. These results represent a first step toward development of gene therapies for one of the more common forms of childhood blindness.

  14. Retinite por citomegalovirus (CMV após terapia imunossupressora para vasculite leucocitoclástica Cytomegalovirus (CMV retinitis after immunossupressive therapy for leukocytoclastic vasculitis

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    Carlos Ewerton Maia Rodrigues


    Full Text Available A retinite por citomegalovírus (CMV é uma doença rara que acomete principalmente pacientes com a síndrome da imunodeficiência adquirida (AIDS. No entanto, outros pacientes imunossuprimidos, como os transplantados, os que estão em uso de quimioterápicos, pacientes com lúpus eritematoso sistêmico (LES ou em tratamento com drogas imunossupressoras também podem ser acometidos. O quadro clínico caracteriza-se por visão turva, diminuição da acuidade ou alterações de campo visual, geralmente unilateral, podendo ocorrer deslocamento de retina. A perda visual é progressiva, evolui em ritmo variável até a completa amaurose do olho acometido. O presente relato de caso descreve um paciente com vasculite leucocitoclástica grave submetido à terapia com corticoide em dose imunossupressora que evoluiu com glaucoma, panuveíte por CMV, perda da acuidade visual e infecção bacteriana secundária.Cytomegalovirus (CMV retinitis is a rare disease which mainly affects patients with acquired immunodeficiency syndrome (AIDS. Nevertheless, other immunosuppressed patients, such as the organ transplant recipients, the ones using chemotherapy, patients with systemic lupus erythematosus (SLE or in treatment with immunosuppressive drugs can also be attacked. The clinical characteristics are blurred vision, decrease of the visual acuity or visual field alterations, generally unilateral, with the possibility of retinal detachment. The visual loss is progressive, evolving in a variable rate until complete amaurosis of the attacked eye. The present case report describes a patient with severe leukocytoclastic vasculitis, submitted to corticosteroid therapy in immunosuppressive doses that evolved with glaucoma, panuveitis by CMV, loss of visual acuity and secondary bacterial infection.


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    Snezana TALEVSKA


    Full Text Available The binocular function of the eyesight as a process develops as early as the first years of life.Taking into consideration the great number of inherent factors, which disturb the normal development of the eye-sight function, and the great number of causes of damages in the prenatal and natal period, the question of early detection of the reasons, diagnostics and treatment are of utmost importance.That’s possible, only if there is a cooperation among persons that are in the closest contacts with the child:· the mother;· the pediatrician;· the nurse;· the ophthalmologist;· the educator and· the physician.It’s not so necessary to talk about the importance of the sight in the human life, i.e. the importance of the binocular function of the children sight, from the early age when their psycho-physical development is the most flourishing.The importance of the early detection, diagnostics and treatment of the damaged eyesight is great. Especially, this is of great importance for ambliopia, which can be hardly detected at this early period, but it can be easily and successfully treated. We say it is hard to detect because of the delusion and inertness of parents, just during early years from birth to the 3 year, that the child is small and it’s too early to start a treatment.On the contrary, practice has shown that this time is lost and hardly can be compensate, either in means of cure of ambliopia and treatment or rehabilitation of amaurosis.The numerical data of children with damaged eyesight on the territory of Skopje and the need of organized work with this population of children at preschool age will be confirmed and enclosed.

  16. Gene therapy on demand: site specific regulation of gene therapy. (United States)

    Jazwa, Agnieszka; Florczyk, Urszula; Jozkowicz, Alicja; Dulak, Jozef


    Since 1990 when the first clinical gene therapy trial was conducted, much attention and considerable promise have been given to this form of treatment. Gene therapy has been used with success in patients suffering from severe combined immunodeficiency syndromes (X-SCID and ADA-deficiency), Leber's congenital amaurosis, hemophilia, β-thalassemia and adrenoleukodystrophy. Last year, the first therapeutic vector (Glybera) for treatment of lipoprotein lipase deficiency has been registered in the European Union. Nevertheless, there are still several numerous issues that need to be improved to make this technique more safe, effective and easily accessible for patients. Introduction of the therapeutic gene to the given cells should provide the level of expression which will restore the production of therapeutic protein to normal values or will provide therapeutic efficacy despite not fully physiological expression. However, in numerous diseases the expression of therapeutic genes has to be kept at certain level for some time, and then might be required to be switched off to be activated again when worsening of the symptoms may aggravate the risk of disease relapse. In such cases the promoters which are regulated by local conditions may be more required. In this article the special emphasis is to discuss the strategies of regulation of gene expression by endogenous stimuli. Particularly, the hypoxia- or miRNA-regulated vectors offer the possibilities of tight but, at the same time, condition-dependent and cell-specific expression. Such means have been already tested in certain pathophysiological conditions. This creates the chance for the translational approaches required for development of effective treatments of so far incurable diseases.

  17. Updates on current advances in gene therapy. (United States)

    Tani, Jowy; Faustine; Sufian, Jomiany Tani


    Gene therapy is the attempt to treat diseases by means of genetic manipulation. Numerous challenges remain to be overcome before it becomes available as a safe and effective treatment option. Retroviruses and adenoviruses are among the most commonly used viral vectors in trials. The retrovirus introduces the gene it carries into the target cell genome while the adenovirus introduces the gene into the target cell nucleus without incorporating it into the target cell genome. Other viral vectors such as adeno-associated viruses, pseudotyped viruses and herpes simplex viruses, are also gaining popularity. Proposed non-viral methods for gene transfer include physical methods and the employment of chemical vectors (lipoplexes, polyplexes and inorganic nanoparticles). Recent studies have investigated potential applications of gene therapy in correcting genetic diseases, treating malignant disorders and for treatment of other diseases. Trials on gene therapy for SCID and Leber's congenital amaurosis have achieved considerable success, but the widely publicized adverse reaction in X-linked SCID patient receiving gene therapy raised concerns for safety profile of gene therapy. For that, several methods of improving safety and efficacy of gene therapy have been proposed. At present, the three main gene therapy strategies for treatment of cancer are application to oncolytic viruses, suicide-gene therapy and gene-based immunotherapy. Gendicine, the first approved anticancer drugs based on the use of gene therapy principle, is based on the use of oncolytic viruses. More evidence for wider clinical applications of gene therapy are expected as more gene therapy studies progress from the preclinical phase to clinical trial.

  18. Atypical clinical presentation and long-term survival in a patient with optic nerve medulloepithelioma: a case report

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    Pastora-Salvador Natalia


    Full Text Available Abstract Introduction Medulloepithelioma is a rare congenital tumor of the primitive medullary neuroepithelium. A significant proportion of patients with medulloepithelioma arising from the optic nerve die from intracranial spread or cerebral metastasis. Because it has no known distinct clinical features and because of its low frequency, this tumor presents within the first two to six years of life and is usually misdiagnosed clinically as a different type of optic nerve tumor. Here, we describe a new and atypical case of medulloepithelioma of the optic nerve in a 12-year-old boy. To the best of our knowledge, he is the oldest reported patient to present with this disease and, now as an adult, has the longest documented period of disease-free survival. Case presentation A 12-year-old Caucasian boy with headache and unilateral amaurosis was referred for a presumed optic nerve glioma to our hospital. A computed tomography scan showed optic nerve enlargement, and fundoscopy showed a whitish mass at the optic disc. Our patient had been followed at his local hospital for four years for an 'optic disc cyst' with no change or progression. He experienced mild progressive visual impairment during that period. He was admitted for resection, and a histopathological analysis revealed a medulloepithelioma of the optic nerve. Supplemental orbital radiotherapy was performed. He remained disease-free for 25 years. Conclusions Medulloepithelioma of the optic nerve can clinically mimic more common pediatric tumors, such as optic glioma, meningioma, or retinoblastoma. Thus, medulloepithelioma should be included in the differential diagnoses of pediatric optic nerve lesions. Fundoscopy in these patients may provide relevant information for diagnosis. Anterior optic nerve medulloepitheliomas may behave differently from and have a better prognosis than medulloepitheliomas that have a more posterior location. Our case report illustrates that long-term survival can be

  19. Dawn of ocular gene therapy: implications for molecular diagnosis in retinal disease (United States)

    Jacques, ZANEVELD; Feng, WANG; Xia, WANG; Rui, CHEN


    Personalized medicine aims to utilize genomic information about patients to tailor treatment. Gene replacement therapy for rare genetic disorders is perhaps the most extreme form of personalized medicine, in that the patients’ genome wholly determines their treatment regimen. Gene therapy for retinal disorders is poised to become a clinical reality. The eye is an optimal site for gene therapy due to the relative ease of precise vector delivery, immune system isolation, and availability for monitoring of any potential damage or side effects. Due to these advantages, clinical trials for gene therapy of retinal diseases are currently underway. A necessary precursor to such gene therapies is accurate molecular diagnosis of the mutation(s) underlying disease. In this review, we discuss the application of Next Generation Sequencing (NGS) to obtain such a diagnosis and identify disease causing genes, using retinal disorders as a case study. After reviewing ocular gene therapy, we discuss the application of NGS to the identification of novel Mendelian disease genes. We then compare current, array based mutation detection methods against next NGS-based methods in three retinal diseases: Leber’s Congenital Amaurosis, Retinitis Pigmentosa, and Stargardt’s disease. We conclude that next-generation sequencing based diagnosis offers several advantages over array based methods, including a higher rate of successful diagnosis and the ability to more deeply and efficiently assay a broad spectrum of mutations. However, the relative difficulty of interpreting sequence results and the development of standardized, reliable bioinformatic tools remain outstanding concerns. In this review, recent advances NGS based molecular diagnoses are discussed, as well as their implications for the development of personalized medicine. PMID:23393028

  20. Retinal degeneration associated with RDH12 mutations results from decreased 11-cis retinal synthesis due to disruption of the visual cycle. (United States)

    Thompson, Debra A; Janecke, Andreas R; Lange, Jessica; Feathers, Kecia L; Hübner, Christian A; McHenry, Christina L; Stockton, David W; Rammesmayer, Gabriele; Lupski, James R; Antinolo, Guillermo; Ayuso, Carmen; Baiget, Montserrat; Gouras, Peter; Heckenlively, John R; den Hollander, Anneke; Jacobson, Samuel G; Lewis, Richard A; Sieving, Paul A; Wissinger, Bernd; Yzer, Suzanne; Zrenner, Eberhart; Utermann, Gerd; Gal, Andreas


    Retinoid dehydrogenases/reductases catalyze key oxidation-reduction reactions in the visual cycle that converts vitamin A to 11-cis retinal, the chromophore of the rod and cone photoreceptors. It has recently been shown that mutations in RDH12, encoding a retinol dehydrogenase, result in severe and early-onset autosomal recessive retinal dystrophy (arRD). In a cohort of 1011 individuals diagnosed with arRD, we have now identified 20 different disease-associated RDH12 mutations, of which 16 are novel, in a total of 22 individuals (2.2%). Haplotype analysis suggested a founder mutation for each of the three common mutations: p.L99I, p.T155I and c.806_810delCCCTG. Patients typically presented with early disease that affected the function of both rods and cones and progressed to legal blindness in early adulthood. Eleven of the missense variants identified in our study exhibited profound loss of catalytic activity when expressed in transiently transfected COS-7 cells and assayed for ability to convert all-trans retinal to all-trans retinol. Loss-of-function appeared to result from decreased protein stability, as expression levels were significantly reduced. For the p.T49M variant, differing activity profiles were associated with each of the alleles of the common p.R161Q RDH12 polymorphism, suggesting that genetic background may act as a modifier of mutation effect. A locus (LCA3) for Leber congenital amaurosis, a severe, early-onset form of arRD, maps close to RDH12 on chromosome 14q24. Haplotype analysis in the family in which LCA3 was mapped excluded RDH12 as the LCA3 gene and thus suggests the presence of a novel arRD gene in this region.

  1. Genome-wide association study in RPGRIP1(-/-) dogs identifies a modifier locus that determines the onset of retinal degeneration. (United States)

    Miyadera, Keiko; Kato, Kumiko; Boursnell, Mike; Mellersh, Cathryn S; Sargan, David R


    Cone-rod dystrophy (CRD) is a form of inherited retinal degeneration (RD) causing blindness in man as well as in several breeds of dog. Previously, a 44 bp insertion in RPGRIP1 (retinitis pigmentosa GTPase regulator interacting protein-1) was associated with a recessive early-onset CRD (cone-rod dystrophy 1, cord1) in a Miniature longhaired dachshund (MLHD) research colony. Yet in the MLHD pet population, extensive range of the onset age has been observed among RD cases, with some RPGRIP1(-/-) dogs lacking obvious clinical signs. Phenotypic variation has been known in human homologous diseases, including retinitis pigmentosa and Leber congenital amaurosis, indicating possible involvement of modifiers. To explore additional genetic loci associated with the phenotypic variation observed in MLHDs, a genome-wide association study was carried out using Canine SNP20 arrays in 83 RPGRIP1(-/-) MLHDs with variable ages of onset or no clinical abnormality. Using these samples, comparison of 31 early-onset RD cases against 49 controls (15 late-onset RD and 34 normal dogs combined) identified a strong association (P = 5.05 × 10(-13)) at a single locus on canine chromosome 15. At this locus, the majority of early-onset RD cases but few of the controls were homozygous for a 1.49 Mb interval containing ~11 genes. We conclude that homozygosity at both RPGRIP1 and the newly mapped second locus is necessary to develop early-onset RD, whereas RPGRIP1(-/-) alone leads to late-onset RD or no apparent clinical phenotype. This study establishes a unique model of canine RD requiring homozygous mutations at two distinct genetic loci for the manifestation of early-onset RD.

  2. Noninvasive, in vivo assessment of mouse retinal structure using optical coherence tomography.

    Directory of Open Access Journals (Sweden)

    M Dominik Fischer

    Full Text Available BACKGROUND: Optical coherence tomography (OCT is a novel method of retinal in vivo imaging. In this study, we assessed the potential of OCT to yield histology-analogue sections in mouse models of retinal degeneration. METHODOLOGY/PRINCIPAL FINDINGS: We achieved to adapt a commercial 3(rd generation OCT system to obtain and quantify high-resolution morphological sections of the mouse retina which so far required in vitro histology. OCT and histology were compared in models with developmental defects, light damage, and inherited retinal degenerations. In conditional knockout mice deficient in retinal retinoblastoma protein Rb, the gradient of Cre expression from center to periphery, leading to a gradual reduction of retinal thickness, was clearly visible and well topographically quantifiable. In Nrl knockout mice, the layer involvement in the formation of rosette-like structures was similarly clear as in histology. OCT examination of focal light damage, well demarcated by the autofluorescence pattern, revealed a practically complete loss of photoreceptors with preservation of inner retinal layers, but also more subtle changes like edema formation. In Crb1 knockout mice (a model for Leber's congenital amaurosis, retinal vessels slipping through the outer nuclear layer towards the retinal pigment epithelium (RPE due to the lack of adhesion in the subapical region of the photoreceptor inner segments could be well identified. CONCLUSIONS/SIGNIFICANCE: We found that with the OCT we were able to detect and analyze a wide range of mouse retinal pathology, and the results compared well to histological sections. In addition, the technique allows to follow individual animals over time, thereby reducing the numbers of study animals needed, and to assess dynamic processes like edema formation. The results clearly indicate that OCT has the potential to revolutionize the future design of respective short- and long-term studies, as well as the preclinical

  3. Analysis of atypical symptomes at onset in 21 patients with subarachnoid hemorrhage%首发症状不典型的蛛网膜下腔出血21例分析

    Institute of Scientific and Technical Information of China (English)

    朱琳; 王翀


    目的 分析蛛网膜下腔出血(SAH)首发症状不典型的产生机制和误诊原因,以提高早期诊断水平.方法 对2006-2010年诊治的21例首发症状不典型的SAH患者的临床资料进行回顾性分析.结果 首发症状为头痛但无脑膜刺激征者5例;意识障碍者4例;眩晕者3例;偏瘫者2例;颈痛者2例;腰腿痛2例;精神异常者1例;抽搐者1例;头昏、黑朦1例.结论 熟知SAH的不典型首发症状,对不能排除SAH的患者应尽早、合理完善辅助检查,以减少误诊、漏诊.%Objective To analyze the mechanism of production of atypical symptoms at onset of subaraehnoid hemorrhage( SAH ) and the reasons of misdiagnosis. Methods The clinical data of 21 SAH patients with atypical symptoms at onset within 2006-2010 were retrospectively studied. Results 5 patients with atypical symptome at onset of headache without signs of meningeal irritation;4 patients with disturbance of consciousness; 3 patients with vertigo ;2 patients with hemiplegia;2 patients with pain of neck; 2 patients with lumbocrural pain;1 patient with psychological problem; 1 patient with convulsion; 1 patient with dizziness and amaurosis. Conclusions To decrease misdiagnosis and missed diagnosis, clinical doctors should be familiar with atypical symptoms at onset of SAH and suggest patients who are SAH possibly to complete accessory examination reasonably and as soon as possible.

  4. Distilling a Visual Network of Retinitis Pigmentosa Gene-Protein Interactions to Uncover New Disease Candidates.

    Directory of Open Access Journals (Sweden)

    Daniel Boloc

    Full Text Available Retinitis pigmentosa (RP is a highly heterogeneous genetic visual disorder with more than 70 known causative genes, some of them shared with other non-syndromic retinal dystrophies (e.g. Leber congenital amaurosis, LCA. The identification of RP genes has increased steadily during the last decade, and the 30% of the cases that still remain unassigned will soon decrease after the advent of exome/genome sequencing. A considerable amount of genetic and functional data on single RD genes and mutations has been gathered, but a comprehensive view of the RP genes and their interacting partners is still very fragmentary. This is the main gap that needs to be filled in order to understand how mutations relate to progressive blinding disorders and devise effective therapies.We have built an RP-specific network (RPGeNet by merging data from different sources: high-throughput data from BioGRID and STRING databases, manually curated data for interactions retrieved from iHOP, as well as interactions filtered out by syntactical parsing from up-to-date abstracts and full-text papers related to the RP research field. The paths emerging when known RP genes were used as baits over the whole interactome have been analysed, and the minimal number of connections among the RP genes and their close neighbors were distilled in order to simplify the search space.In contrast to the analysis of single isolated genes, finding the networks linking disease genes renders powerful etiopathological insights. We here provide an interactive interface, RPGeNet, for the molecular biologist to explore the network centered on the non-syndromic and syndromic RP and LCA causative genes. By integrating tissue-specific expression levels and phenotypic data on top of that network, a more comprehensive biological view will highlight key molecular players of retinal degeneration and unveil new RP disease candidates.

  5. Postretinal Structure and Function in Severe Congenital Photoreceptor Blindness Caused by Mutations in the GUCY2D Gene (United States)

    Aguirre, Geoffrey K.; Butt, Omar H.; Datta, Ritobrato; Roman, Alejandro J.; Sumaroka, Alexander; Schwartz, Sharon B.; Cideciyan, Artur V.; Jacobson, Samuel G.


    Purpose To examine how severe congenital blindness resulting from mutations of the GUCY2D gene alters brain structure and function, and to relate these findings to the notable preservation of retinal architecture in this form of Leber congenital amaurosis (LCA). Methods Six GUCY2D-LCA patients (ages 20–46) were studied with optical coherence tomography of the retina and multimodal magnetic resonance imaging (MRI) of the brain. Measurements from this group were compared to those obtained from populations of normally sighted controls and people with congenital blindness of a variety of causes. Results Patients with GUCY2D-LCA had preservation of the photoreceptors, ganglion cells, and nerve fiber layer. Despite this, visual function in these patients ranged from 20/160 acuity to no light perception, and functional MRI responses to light stimulation were attenuated and restricted. This severe visual impairment was reflected in substantial thickening of the gray matter layer of area V1, accompanied by an alteration of resting-state correlations within the occipital lobe, similar to a comparison group of congenitally blind people with structural damage to the retina. In contrast to the comparison blind population, however, the GUCY2D-LCA group had preservation of the size of the optic chiasm, and the fractional anisotropy of the optic radiations as measured with diffusion tensor imaging was also normal. Conclusions These results identify dissociable effects of blindness upon the visual pathway. Further, the relatively intact postgeniculate white matter pathway in GUCY2D-LCA is encouraging for the prospect of recovery of visual function with gene augmentation therapy.

  6. Molecular anthropology meets genetic medicine to treat blindness in the North African Jewish population: human gene therapy initiated in Israel. (United States)

    Banin, Eyal; Bandah-Rozenfeld, Dikla; Obolensky, Alexey; Cideciyan, Artur V; Aleman, Tomas S; Marks-Ohana, Devora; Sela, Malka; Boye, Sanford; Sumaroka, Alexander; Roman, Alejandro J; Schwartz, Sharon B; Hauswirth, William W; Jacobson, Samuel G; Hemo, Itzhak; Sharon, Dror


    The history of the North African Jewish community is ancient and complicated with a number of immigration waves and persecutions dramatically affecting its population size. A decade-long process in Israel of clinical-molecular screening of North African Jews with incurable autosomal recessive blindness led to the identification of a homozygous splicing mutation (c.95-2A > T; IVS2-2A > T) in RPE65, the gene encoding the isomerase that catalyzes a key step in the retinoid-visual cycle, in patients from 10 unrelated families. A total of 33 patients (four now deceased) had the severe childhood blindness known as Leber congenital amaurosis (LCA), making it the most common cause of retinal degeneration in this population. Haplotype analysis in seven of the patients revealed a shared homozygous region, indicating a population-specific founder mutation. The age of the RPE65 founder mutation was estimated to have emerged 100-230 (mean, 153) generations ago, suggesting it originated before the establishment of the Jewish community in North Africa. Individuals with this RPE65 mutation were characterized with retinal studies to determine if they were candidates for gene replacement, the recent and only therapy to date for this otherwise incurable blindness. The step from molecular anthropological studies to application of genetic medicine was then taken, and a representative of this patient subgroup was treated with subretinal rAAV2-RPE65 gene therapy. An increase in vision was present in the treated area as early as 15 days after the intervention. This process of genetically analyzing affected isolated populations as a screen for gene-based therapy suggests a new paradigm for disease diagnosis and treatment.

  7. The Pathway From Genes to Gene Therapy in Glaucoma: A Review of Possibilities for Using Genes as Glaucoma Drugs. (United States)

    Borrás, Teresa


    Treatment of diseases with gene therapy is advancing rapidly. The use of gene therapy has expanded from the original concept of re-placing the mutated gene causing the disease to the use of genes to con-trol nonphysiological levels of expression or to modify pathways known to affect the disease. Genes offer numerous advantages over conventional drugs. They have longer duration of action and are more specific. Genes can be delivered to the target site by naked DNA, cells, nonviral, and viral vectors. The enormous progress of the past decade in molecular bi-ology and delivery systems has provided ways for targeting genes to the intended cell/tissue and safe, long-term vectors. The eye is an ideal organ for gene therapy. It is easily accessible and it is an immune-privileged site. Currently, there are clinical trials for diseases affecting practically every tissue of the eye, including those to restore vision in patients with Leber congenital amaurosis. However, the number of eye trials compared with those for systemic diseases is quite low (1.8%). Nevertheless, judg-ing by the vast amount of ongoing preclinical studies, it is expected that such number will increase considerably in the near future. One area of great need for eye gene therapy is glaucoma, where a long-term gene drug would eliminate daily applications and compliance issues. Here, we review the current state of gene therapy for glaucoma and the possibilities for treating the trabecular meshwork to lower intraocular pressure and the retinal ganglion cells to protect them from neurodegeneration.

  8. The clinical spectrum of inherited diseases involved in the synthesis and remodeling of complex lipids. A tentative overview. (United States)

    Garcia-Cazorla, Àngels; Mochel, Fanny; Lamari, Foudil; Saudubray, Jean-Marie


    Over one hundred diseases related to inherited defects of complex lipids synthesis and remodeling are now reported. Most of them were described within the last 5 years. New descriptions and phenotypes are expanding rapidly. While the associated clinical phenotype is currently difficult to outline, with only a few patients identified, it appears that all organs and systems may be affected. The main clinical presentations can be divided into (1) Diseases affecting the central and peripheral nervous system. Complex lipid synthesis disorders produce prominent motor manifestations due to upper and/or lower motoneuron degeneration. Motor signs are often complex, associated with other neurological and extra-neurological signs. Three neurological phenotypes, spastic paraparesis, neurodegeneration with brain iron accumulation and peripheral neuropathies, deserve special attention. Many apparently well clinically defined syndromes are not distinct entities, but rather clusters on a continuous spectrum, like for the PNPLA6-associated diseases, extending from Boucher-Neuhauser syndrome via Gordon Holmes syndrome to spastic ataxia and pure hereditary spastic paraplegia; (2) Muscular/cardiac presentations; (3) Skin symptoms mostly represented by syndromic (neurocutaneous) and non syndromic ichthyosis; (4) Retinal dystrophies with syndromic and non syndromic retinitis pigmentosa, Leber congenital amaurosis, cone rod dystrophy, Stargardt disease; (5) Congenital bone dysplasia and segmental overgrowth disorders with congenital lipomatosis; (6) Liver presentations characterized mainly by transient neonatal cholestatic jaundice and non alcoholic liver steatosis with hypertriglyceridemia; and (7) Renal and immune presentations. Lipidomics and molecular functional studies could help to elucidate the mechanism(s) of dominant versus recessive inheritance observed for the same gene in a growing number of these disorders.

  9. [Surgical management of paraclinoid aneurysms]. (United States)

    Magallón-Barajas, Eduardo; Abdo-Toro, Miguel; Flores-Robles, Claudia


    Introducción: los aneurismas paraclinoideos se originan en los segmentos clinoideo C5 y oftálmico C6 de la arteria carótida interna. Su frecuencia aproximada es del 5 al 11 %. Para su manejo microquirúrgico se requiere de un conocimiento anatómico de la región y del aneurisma. El objetivo es mostrar el manejo neuroquirúrgico de los aneurismas paraclinoideos. Métodos: se hizo un estudio retrospectivo en un servicio de neurocirugía, de enero de 2009 a enero de 2015. Se incluyeron 66 pacientes con aneurisma paraclinoideo. Se obtuvieron las características clínicas, la evolución, las complicaciones y los resultados de los pacientes al revisar los expedientes clínicos y radiológicos. Resultados: 61 pacientes (92.4 %) pertenecieron al sexo femenino; a 65 se les realizó clipaje neuroquirúrgico y a uno se le realizó bypass cerebral con exclusión del aneurisma. Tuvieron ruptura del aneurisma con hemorragia subaracnoidea 46 pacientes. Por su localización 35 aneurismas paraclinoideos (53 %) fueron superiores, 20 mediales (30.3 %) y cuatro inferiores (6 %). Tuvieron aneurismas pequeños 33 pacientes (50 %), 23 grandes (34.8 %) y 10 gigantes (15.5 %). Presentaron buenos resultados 51 pacientes después del manejo quirúrgico, dado que sacaron calificaciones de 4 y 5 según el Glasgow Outcome Score (GOS). La amaurosis fue la complicación funcional más seria atribuible a la cirugía (tres pacientes). Conclusión: la microcirugía sigue siendo el tratamiento para estos aneurismas debido a su capacidad de excluirlos totalmente, además de que es el mejor método para descomprimir el nervio óptico.

  10. Dog as a model in studies on human hereditary diseases and their gene therapy. (United States)

    Switonski, Marek


    During the last 15 years spectacular progress has been achieved in knowledge on the dog genome organization and the molecular background of hereditary diseases in this species. A majority of canine genetic diseases have their counterparts in humans and thus dogs are considered as a very important large animal model in human biomedicine. Among canine monogenic diseases with known causative gene mutations there are two large groups classified as retinal dystrophies and lysosomal storage diseases. Specific types of these diseases are usually diagnosed in a single or several breeds. A well known disorder, restricted to a single breed, is congenital stationary night blindness described in Briards. This disease is a counterpart of Leber amaurosis in children. On the other hand, one of the most common monogenic human diseases (Duchenne muscular dystrophy), has its canine counterparts in several breeds (e.g., the Golden retriever, Beagle and German short-haired pointer). For some of the canine diseases gene therapy strategy was successfully applied, e.g., for congenital stationary night blindness, rod-cone dystrophy and muccopolysaccharydoses type I, IIIB and VII. Since phenotypic variability between the breeds is exceptionally high, the dog is an interesting model to study the molecular background of congenital malformations (e.g., dwarfism and osteoporosis imperfecta). Also disorders of sexual development (DSD), especially testicular or ovotesticular DSD (78,XX; SRY-negative), which is widely distributed across dozens of breeds, are of particular interest. Studies on the genetic background of canine cancers, a major health problem in this species, are also quite advanced. On the other hand, genetic studies on canine counterparts of major human complex diseases (e.g., obesity, the metabolic syndrome and diabetes mellitus) are still in their infancy.

  11. 慢性便秘伴发肛门直肠疼痛的全国多中心分层调查研究%Multi-centered stratified study of chronic constipation with anorectal pain in China

    Institute of Scientific and Technical Information of China (English)

    辛海威; 方秀才; 高峻; 刘诗; 肖英莲; 张军; 朱丽明; 王智凤; 柯美云


    Objective To investigate the prevalence of anorectal pain in chronic constipation (CO patients. Methods With multi-centered stratified questionnaires investigation,the face to face questionnaires investigation was carried out on the symptoms of constipation and intensity,frequency and duration of anorectal pain in CC patients. CC and anorectal pain was diagnosed according to Rome Ⅲ criteria. Results Total 921 CC patients were investigated,and 909 questionnaires were valid. Of those,there were 258 male cases and 651 female cases,the mean age was(48. 9±18. 7)years. About 15. 1%(137/909)CC patients reported anorectal pain in last six months;of those 26 cases(2. 9%)with chronic proctalgia(CP),111 cases(12. 2%)with proctalgia fugax(PF). The percentage of pain occurred frequently or regularly in CP and PF patients was 88. 5%(23/26)and 73. 9%(82/111)respectively. The pain of PF patients was milder than that of CP patients. The detection rate of CP was higher in tertiary hospitals than in primary cares(3. 6% vs 0. 6%,P= 0. 04). There was no significant difference of PF detection rate between different hospitals(P= 0. 09). The occurrence of pain was associated with anorectal symptoms,sleeping and psychosocial condition. Conclusions CC patients are frequently with anorectal pain and more common in female,which should cause extensive concern by physicians.If necessary,the prevalence of anorectal pain in general population as well as the mechanism of the symptom need further investigation.%目的 调查慢性便秘患者伴发肛门直肠疼痛情况.方法 采用全国多中心分层问卷调查,纳入慢性便秘患者后就便秘症状、肛门直肠疼痛程度、频率及持续时间等进行面对面问卷调查.慢性便秘与肛门直肠疼痛的判断均参考罗马Ⅲ诊断标准.结果 共凋查921例慢性便秘患者,有效问卷909份,其中男性258例、女性651例,平均年龄(48.9±18.7)岁.15.1%(137/909)的慢性便秘患者最近6个月有肛门直肠

  12. Impact of set-aside management on soil mesofauna (United States)

    Landi, Silvia; d'Errico, Giada; Mazza, Giuseppe; Mocali, Stefano; Bazzoffi, Paolo; Roversi, Pio Federico


    (MI) resulted significantly higher in set-aside managements than in conventional crops in Fagna and Metaponto sites. In contrast, Caorle was characterized by a significant soil degradation (prevalence of extreme colonizers) and any increase of MI values in the set-aside have been not detected. About microarthropods, the taxa richness was significantly higher in set-aside managements than conventional crops in all the sites sampled. QBS index showed the same trend, but the differences were not significant. Caorle site was characterized by a lack of balance in the relative abundance among soil microarthropods taxa. In particular, set-aside managements showed a strong prevalence of an aggressive ants Solenopsis fugax (Hymenoptera: Formicidae). In conclusion, the best results were observed in Fagna and Metaponto sites, where MI and QBS values increased under set-aside management as compared to the conventional. Further analyses will be carried out over a long period to better understand the possible correlation between the enhancement of the organic matter observed in the soils less degraded and the biological quality improvement.

  13. [Stroke. are there any difference between patients with or without patent foramen ovale in left atrial appendage systolic function?]. (United States)

    Contreras, Alejandro E; Perrote, Federico; Concari, Ignacio; Brenna, Eduardo J; Lucero, Cecilia


    Introducción: El objetivo del presente trabajo fue comparar la función sistólica de la orejuela de la aurícula izquierda (OAI) en un grupo de pacientes con y sin foramen oval permeable (FOP) quienes sufrieron eventos cerebrovasculares isquémicos. Material y métodos: Entre septiembre de 2010 y octubre de 2011, 17 pacientes fueron enviados para la realización de un ecocardiograma transesofágico (ETE) por haber sufrido un accidente cerebrovascular (ACV). Se definió FOP al pasaje de al menos una burbuja a través del septum interauricular con test de burbujas. Se comparó la velocidad sistólica en la orejuela entre los pacientes con y sin FOP y con un grupo control. Resultados: Fueron 8 mujeres y 9 hombres, con una edad media de 54,1 ± 19,5 años. Todos los pacientes habían sufrido un evento cerebrovascular isquémico, el 41,2% habían tenido ACV, el 52,9% crisis isquémica transitoria y el 5,9% amaurosis fugaz. En la evaluación con ETE, el 11,8% tuvo aneurisma del septum interauricular y el 35,3% FOP. La velocidad sistólica media de la OAI fue 66,3 ± 20,3 cm/seg. No hubo diferencia en la velocidad sistólica de la OAI entre pacientes con o sin FOP (67,5 ± 11,8 cm/seg vs 65,7 ± 24,3 cm/seg respectivamente, p= 0,87). El grupo control compuesto por 8 pacientes, 5 mujeres y 3 hombres, con una edad media de 39,5 ± 18 años, tuvo una velocidad sistólica de la OAI de 77,6 ± 28,9 cm/seg, sin diferencias significativas con los pacientes isquémicos. Conclusión: No hubo diferencias en la función sistólica de la OAI entre pacientes con y sin FOP con eventos cerebrovasculares isquemicos.

  14. Union makes strength: a worldwide collaborative genetic and clinical study to provide a comprehensive survey of RD3 mutations and delineate the associated phenotype.

    Directory of Open Access Journals (Sweden)

    Isabelle Perrault

    Full Text Available Leber congenital amaurosis (LCA is the earliest and most severe retinal degeneration (RD, and the most common cause of incurable blindness diagnosed in children. It is occasionally the presenting symptom of multisystemic ciliopathies which diagnosis will require a specific care of patients. Nineteen LCA genes are currently identified and three of them account for both non-syndromic and syndromic forms of the disease. RD3 (LCA12 was implicated as a LCA gene based on the identification of homozygous truncating mutations in two LCA families despite the screening of large cohorts of patients. Here we provide a comprehensive survey of RD3 mutations and of their clinical expression through the screening of a cohort of 852 patients originating worldwide affected with LCA or early-onset and severe RD. We identified three RD3 mutations in seven unrelated consanguineous LCA families - i.e., a 2 bp deletion and two nonsense mutations - predicted to cause complete loss of function. Five families originating from the Southern Shores of the Mediterranean segregated a similar mutation (c.112C>T, p.R38* suggesting that this change may have resulted from an ancient founder effect. Considering the low frequency of RD3 carriers, the recurrence risk for LCA in non-consanguineous unions is negligible for both heterozygote and homozygote RD3 individuals. The LCA12 phenotype in our patients is highly similar to those of patients with mutant photoreceptor-specific guanylate cyclase (GUCY2D/LCA1. This observation is consistent with the report of the role of RD3 in trafficking of GUCYs and gives further support to a common mechanism of photoreceptor degeneration in LCA12 and LCA1, i.e., inability to increase cytoplasmic cGMP concentration in outer segments and thus to recover the dark-state. Similar to LCA1, LCA12 patients have no extraocular symptoms despite complete inactivation of both RD3 alleles, supporting the view that extraocular investigations in LCA infants

  15. Union makes strength: a worldwide collaborative genetic and clinical study to provide a comprehensive survey of RD3 mutations and delineate the associated phenotype. (United States)

    Perrault, Isabelle; Estrada-Cuzcano, Alejandro; Lopez, Irma; Kohl, Susanne; Li, Shiqiang; Testa, Francesco; Zekveld-Vroon, Renate; Wang, Xia; Pomares, Esther; Andorf, Jean; Aboussair, Nisrine; Banfi, Sandro; Delphin, Nathalie; den Hollander, Anneke I; Edelson, Catherine; Florijn, Ralph; Jean-Pierre, Marc; Leowski, Corinne; Megarbane, Andre; Villanueva, Cristina; Flores, Blanca; Munnich, Arnold; Ren, Huanan; Zobor, Ditta; Bergen, Arthur; Chen, Rui; Cremers, Frans P M; Gonzalez-Duarte, Roser; Koenekoop, Robert K; Simonelli, Francesca; Stone, Edwin; Wissinger, Bernd; Zhang, Qingjiong; Kaplan, Josseline; Rozet, Jean-Michel


    Leber congenital amaurosis (LCA) is the earliest and most severe retinal degeneration (RD), and the most common cause of incurable blindness diagnosed in children. It is occasionally the presenting symptom of multisystemic ciliopathies which diagnosis will require a specific care of patients. Nineteen LCA genes are currently identified and three of them account for both non-syndromic and syndromic forms of the disease. RD3 (LCA12) was implicated as a LCA gene based on the identification of homozygous truncating mutations in two LCA families despite the screening of large cohorts of patients. Here we provide a comprehensive survey of RD3 mutations and of their clinical expression through the screening of a cohort of 852 patients originating worldwide affected with LCA or early-onset and severe RD. We identified three RD3 mutations in seven unrelated consanguineous LCA families - i.e., a 2 bp deletion and two nonsense mutations - predicted to cause complete loss of function. Five families originating from the Southern Shores of the Mediterranean segregated a similar mutation (c.112C>T, p.R38*) suggesting that this change may have resulted from an ancient founder effect. Considering the low frequency of RD3 carriers, the recurrence risk for LCA in non-consanguineous unions is negligible for both heterozygote and homozygote RD3 individuals. The LCA12 phenotype in our patients is highly similar to those of patients with mutant photoreceptor-specific guanylate cyclase (GUCY2D/LCA1). This observation is consistent with the report of the role of RD3 in trafficking of GUCYs and gives further support to a common mechanism of photoreceptor degeneration in LCA12 and LCA1, i.e., inability to increase cytoplasmic cGMP concentration in outer segments and thus to recover the dark-state. Similar to LCA1, LCA12 patients have no extraocular symptoms despite complete inactivation of both RD3 alleles, supporting the view that extraocular investigations in LCA infants with RD3 mutations

  16. Analysis of Dynamic Electrocardiograms Characteristics in Long R-R Intervals of Atrial Fibrillation%房颤伴长R-R间期的动态心电图特点分析

    Institute of Scientific and Technical Information of China (English)

    丁华民; 戴红艳; 王晏平; 张俊义


    目的 分析房颤合并长R-R间期(>1.5 s)的动态心电图(DCG)特点,探讨DCG对房颤合并房室传导阻滞的诊断价值.方法将DCG记录到的186例房颤伴长R-R间期者分为睡眠相关组和睡眠无关组,分析平均心室率、长R-R间期昼夜发生频度及伴随症状.结果睡眠无关组患者睡眠及非睡眠时平均心室率均小于睡眠相关组;睡眠无关组长R-R间期、逸搏及逸搏心律发生频率明显高于睡眠相关组;睡眠相关组患者长间歇时不伴黑矇或晕厥,而睡眠无关组患者长间歇时有22例出现黑矇或晕厥,均发生在清醒状态时.结论分析房颤患者DCG长R-R间期发生的频度、时间等特征有助于判断生理性或病理性房室传导阻滞.%Objective To analyse the characteristics of dynamic electrocardiograms (DCG) in long R-R intervals of atrial fibrillation (AF), and explore the role of DCG in the diagnosis of atrioventrieular block (AVB) in AF patients. Methods 186 AF patients with long R-R intervals are divided into two groups: sleep-related group and non-sleep-related group, and analysis is accomplished on the average ventricular rates, frequencies of long R-R intervals, and the accompanying symptoms. Results The average ventricular rates are significantly lower in non-sleep-related group than those in sleep-related group, both during sleeping time and non-sleeping time. The frequencies of long R-R intervals, escape beats and escape rhythms are significantly higher in non-sleep-related group compared with sleep-related group. No amaurosis or syncope occurs in sleep-related group, while 22 of such symptoms happen in non-sleep-related group during non-sleeping time. Conclusion Analysis of characteristics of frequencies and time in long R-R intervals of DCG may be helpful in the judgment of physiological or pathological AVB in AF patients.

  17. Union Makes Strength: A Worldwide Collaborative Genetic and Clinical Study to Provide a Comprehensive Survey of RD3 Mutations and Delineate the Associated Phenotype (United States)

    Perrault, Isabelle; Estrada-Cuzcano, Alejandro; Lopez, Irma; Kohl, Susanne; Li, Shiqiang; Testa, Francesco; Zekveld-Vroon, Renate; Wang, Xia; Pomares, Esther; Andorf, Jean; Aboussair, Nisrine; Banfi, Sandro; Delphin, Nathalie; den Hollander, Anneke I.; Edelson, Catherine; Florijn, Ralph; Jean-Pierre, Marc; Leowski, Corinne; Megarbane, Andre; Villanueva, Cristina; Flores, Blanca; Munnich, Arnold; Ren, Huanan; Zobor, Ditta; Bergen, Arthur; Chen, Rui; Cremers, Frans P. M.; Gonzalez-Duarte, Roser; Koenekoop, Robert K.; Simonelli, Francesca; Stone, Edwin; Wissinger, Bernd; Zhang, Qingjiong; Kaplan, Josseline; Rozet, Jean-Michel


    Leber congenital amaurosis (LCA) is the earliest and most severe retinal degeneration (RD), and the most common cause of incurable blindness diagnosed in children. It is occasionally the presenting symptom of multisystemic ciliopathies which diagnosis will require a specific care of patients. Nineteen LCA genes are currently identified and three of them account for both non-syndromic and syndromic forms of the disease. RD3 (LCA12) was implicated as a LCA gene based on the identification of homozygous truncating mutations in two LCA families despite the screening of large cohorts of patients. Here we provide a comprehensive survey of RD3 mutations and of their clinical expression through the screening of a cohort of 852 patients originating worldwide affected with LCA or early-onset and severe RD. We identified three RD3 mutations in seven unrelated consanguineous LCA families - i.e., a 2 bp deletion and two nonsense mutations – predicted to cause complete loss of function. Five families originating from the Southern Shores of the Mediterranean segregated a similar mutation (c.112C>T, p.R38*) suggesting that this change may have resulted from an ancient founder effect. Considering the low frequency of RD3 carriers, the recurrence risk for LCA in non-consanguineous unions is negligible for both heterozygote and homozygote RD3 individuals. The LCA12 phenotype in our patients is highly similar to those of patients with mutant photoreceptor-specific guanylate cyclase (GUCY2D/LCA1). This observation is consistent with the report of the role of RD3 in trafficking of GUCYs and gives further support to a common mechanism of photoreceptor degeneration in LCA12 and LCA1, i.e., inability to increase cytoplasmic cGMP concentration in outer segments and thus to recover the dark-state. Similar to LCA1, LCA12 patients have no extraocular symptoms despite complete inactivation of both RD3 alleles, supporting the view that extraocular investigations in LCA infants with RD3

  18. [Anorexia with sinus bradycardia: a case report]. (United States)

    Wang, Fang-fang; Xu, Ling; Chen, Bao-xia; Cui, Ming; Zhang, Yuan


    As anorexia patients always go to the psychiatric clinic, little is concerned about the occurrence of sinus bradycardia in these patients for cardiologists and psychiatrists. The aim of this paper is to discuss the relationship between anorexia and sinus bradycardia, and the feature analysis, differential diagnosis and therapeutic principles of this type of sinus bradycardia. We report a case of sinus bradycardia in an anorexia patient with the clinical manifestations, laboratory exams, auxiliary exams, therapeutic methods, and her prognosis, who was admitted to Peking University Third Hospital recently. The patient was a 19-year-old female, who had the manifestation of anorexia. She lost obvious weight in a short time (about 15 kg in 6 months), and her body mass index was 14.8 kg/m(2). The patient felt apparent palpitation, chest depression and short breath, without dizziness, amaurosis or unconsciousness. Vitals on presentation were notable for hypotension, and bradycardia. The initial exam was significant for emaciation, but without lethargy or lower extremity edema. The electrocardiogram showed sinus bradycardia with her heart rate being 32 beats per minute. The laboratory work -up revealed her normal blood routine, electrolytes and liver function. But in her thyroid function test, the free thyroid (FT) hormones 3 was 0.91 ng/L (2.3-4.2 ng/L),and FT4 was 8.2 ng/L (8.9-18.0 ng/L), which were all lower; yet the thyroid stimulating hormone (TSH) was normal 1.48 IU/mL (0.55-4.78 IU/mL). Ultrasound revealed her normal thyroid. Anorexia is an eating disorder characterized by extremely low body weight, fear of gaining weight or distorted perception of body image, and amenorrhea. Anorexia patients who lose weight apparently in short time enhance the excitability of the parasympathetic nerve, and inhibit the sympathetic nerve which lead to the appearance of sinus bradycardia, and functional abnormalities of multiple systems such as hypothyroidism. But this kind of sinus

  19. Conhecimento leigo sobre doença vascular encefálica Lay knowledge about stroke

    Directory of Open Access Journals (Sweden)

    Edison Matos Nóvak


    Full Text Available A magnitude das doenças vasculares encefálicas (DVE, com a sua prevalência, gravidade e elevados índices de morbi-mortalidade, faz com que se busquem formas de prevenção e de diagnóstico precoce. Considerando que as informações sobre os fatores de risco e os sintomas de DVE, pelos doentes de risco e pela população em geral, tem um papel preponderante nesta estratégia de tratamento, os autores buscaram conhecer qual o grau deste conhecimento em um grupo populacional amplo e variado. Assim, aplicou-se em 500 pessoas leigas um questionário de que constavam questões sobre os fatores de risco e sobre os sintomas de DVE com termos não médicos. Os resultados da análise estatística mostraram surpreendente conhecimento sobre os fatores de risco, a par de menor reconhecimento sobre os sintomas e sinais de doença vascular. Os autores detalham os achados e comentam sobre este aspecto importante das DVE.The significance of the risk factors and the rapid diagnosis of encephalic vascular disease (EVD is the reason for this research, where the authors decided to register and analyze the non-medical people knowledge about these risk factors and the symptoms of this group of disease. For this purpose a questionnaire with questions about these facts was applied to 500 voluntaries without pre-selection, 72.6% of them with ages between 16-35 years old, and the answers analyzed by statistical methods. The authors recognized that the risk factors has a good level of knowledge by this population (87.8 % for hypertension, 76.8 % for smoking, 70.8 % for obesity, 68.7 % for sedentary persons, 66.7 % to stress, 66.3 % to alcohol ingest, 60.7 % for fat diet, 59 % to illicit drugs while the signs and symptoms of EVD has a minor level of knowing and correction: lost sensitivity 70.3 %, headache 64.2 %, twisted mouth 59.5 %, lost or altered speech 57.5 %, dizziness 56 %, syncope 51.7 %, amaurosis 50.3 %, disequilibrium 45 %, deafness 31.2 %, weakness 41

  20. Neurossífilis atípica: Relato de caso Atypical neurosyphilis: case report

    Directory of Open Access Journals (Sweden)

    Fábio Leite Gastal


    Full Text Available O presente estudo é baseado na observação de um caso de neurossífilis no serviço de internação da Clínica Olivé Leite em agosto-1992. A paciente, do sexo feminino e com 31 anos de idade, foi admitida por apresentar quadro de psicose orgânica no qual predominavam sintomas de tipo deterioração cognitiva (síndrome demencial, associados a elementos paranoides (alucinações e delírios. A investigação diagnóstica evidenciou testes imunológicos positivos para sífilis no sangue e no LCR. Destaca-se este caso pelos seguintes aspectos peculiares: forma da apresentação clínica, gravidade dos sintomas (amaurose e severo déficit cognitivo, sexo, idade e por ser este o primeiro caso diagnosticado no serviço desde 1968 (data do último registro de caso de neurossífilis no seu Banco de Dados. Após penicilinoterapia e seguimento de 9 meses, a paciente apresenta algumas melhoras, caracterizadas por: diminuição da sintomatologia produtiva de tipo alucinatória e delirante, diminuição do déficit cognitivo em termos de orientação e maior produtividade nas atividades sociais e comportamentais.The present study is based on the observation of a case at the inpatient service of Clinica Olivé Leite in August 1992. A 31 years old female patient, showing cognitive deterioration and demential syndrome associated with paranoid elements (hallucination and delirium, was admitted as a case of organic psychosis. Diagnostic investigation evidenced positive tests for syphilis in serum and cerebrospinal fluid. The following peculiar aspects are emphasized in this case: severe clinical presentation, severe presentation symptoms (amaurosis and a severe cognitive deficit, sex, age, and for being the first case diagnosed in the service since 1968 (occasion in wich the last neurosyphilis case was registered in its data bank. In the following nine months, after penicillin therapy, the patient showed some improvement characterized by a reduction of

  1. RETINOBASE: a web database, data mining and analysis platform for gene expression data on retina

    Directory of Open Access Journals (Sweden)

    Léveillard Thierry


    Full Text Available Abstract Background The retina is a multi-layered sensory tissue that lines the back of the eye and acts at the interface of input light and visual perception. Its main function is to capture photons and convert them into electrical impulses that travel along the optic nerve to the brain where they are turned into images. It consists of neurons, nourishing blood vessels and different cell types, of which neural cells predominate. Defects in any of these cells can lead to a variety of retinal diseases, including age-related macular degeneration, retinitis pigmentosa, Leber congenital amaurosis and glaucoma. Recent progress in genomics and microarray technology provides extensive opportunities to examine alterations in retinal gene expression profiles during development and diseases. However, there is no specific database that deals with retinal gene expression profiling. In this context we have built RETINOBASE, a dedicated microarray database for retina. Description RETINOBASE is a microarray relational database, analysis and visualization system that allows simple yet powerful queries to retrieve information about gene expression in retina. It provides access to gene expression meta-data and offers significant insights into gene networks in retina, resulting in better hypothesis framing for biological problems that can subsequently be tested in the laboratory. Public and proprietary data are automatically analyzed with 3 distinct methods, RMA, dChip and MAS5, then clustered using 2 different K-means and 1 mixture models method. Thus, RETINOBASE provides a framework to compare these methods and to optimize the retinal data analysis. RETINOBASE has three different modules, "Gene Information", "Raw Data System Analysis" and "Fold change system Analysis" that are interconnected in a relational schema, allowing efficient retrieval and cross comparison of data. Currently, RETINOBASE contains datasets from 28 different microarray experiments performed

  2. Dynamic electrocardiogram characteristics and prognosis of atrial fibrillation complicated with long R-R interval%心房颤动伴长R-R间期患者动态心电图特点及预后分析

    Institute of Scientific and Technical Information of China (English)

    袁超; 方冬平; 李果; 李玉凤; 王熙; 权薇


    Objective To investigate dynamic electrocardiogram characteristics and prognosis in patients with atrial fibrillation complicated with long R-R interval.Methods Totally 115 patients in Beijing Anzhen Hospital,Capital Medical University from August 2015 to December 2015 were enrolled.The dynamic electrocardiogram examination revealed atrial fibrillation with long R-R interval (> 2 s).Age and long R-R interval distribution were analyzed.According to the occurrence time of long R-R interval,all patients were divided into sleep related group and non-sleep related group.In sleep related group,R-R interval only occurred between 21:00-6:00;in non-sleep related group,R-R interval occurred anytime.Electrocardiogram characteristics and follow-up data were analyzed between groups.Results Long R-R interval could occur in elderly patients with atrial fibrillation,especially between 21:00-6:00.The lowest ventricular rate,the highest ventricular rate,average ventricular rate and times of long R-R interval had significant differences between sleep related group (53 cases) and non-sleep related group (62 cases) (P < 0.05).In sleep related groups,no patient had amaurosis syncope symptom;17 patients got cardioversion and 16 cases among them showed normal dynamic cardiogram performances;1 case was diagnosed of first-degree atrioventricular block;12 patients showed no long R-R interval.In non-sleep related group,amaurosis syncope occurred to 2 patients and they got recovery after artificial pacemaker implantation in hospital;3 patients had second-and third-degree atrioventricular block after cardioversion;1 patient still showed long R-R interval.Conclusion Atrial fibrillation patients with long R-R intervals and low heart rates need regular follow-ups.%目的 探讨心房颤动伴长R-R间期出现原因及预后.方法 选取2015年8-12月首都医科大学附属北京安贞医院门诊及住院患者动态心电图检查显示心房颤动伴>2s长R-R间期的患者115例,分

  3. Analyses of species composition and diversity of weed seed bank of main crop fields in Jiangsu Province and its correlation with environmental factors%江苏省主要农田杂草种子库物种组成和多样性及其与环境因子的相关性分析

    Institute of Scientific and Technical Information of China (English)

    章超斌; 马波; 强胜


    采用水洗镜检法对江苏省31个农田样点(包括旱田和水田)0~15 cm土层土壤杂草种子库的种类组成和物种多样性进行了调查研究;采用典范对应法分析了杂草种子库种类与环境因子(包括淹水天数、土壤有机质含量、土壤pH、年降水量、年均温、样点经度和样点纬度)的相关性并绘制了样点和种类与环境因子的二维排序散点图.调查结果表明:在31个样点的土壤杂草种子库中共检测到杂草种子15科54种,旱田和水田各有41和45种,二者共有种类占多数但优势种有差异,通泉草[ Mazus japonicus (Thunb.) Kuntze]、异型莎草(Cyperus difformis L.)、水苋菜(Ammannia baccifera L.)、千金子[Leptochloa chinensis (L.) Nees]、棒头革(Polypogon fugax Nees ex Steud.)和牛繁缕[ Malachium aquaticum (L.) Fries]等种类为二者的共有优势种;杂草种类最多的为禾本科(Gramineae)和莎草科(Cyperaceae),分别占种类总数的22.6%和20.8%.旱田不同样点杂草种子库的优势种类变化较大,而水田杂草种子库优势种较稳定;二者优势种频度差异较大,旱田中频度高于0.30的杂草有19种,水田中频度高于0.50的杂草有20种;旱田和水田中平均重要值大于0.03的杂草各有11和9种,这些频度高的种类重要值也较大.旱田和水田土壤种子库种子密度分别为21 015和37 847 m-2,平均为31 008 m-2;旱田3层土壤中种子密度差异不显著,而水田上、中层土壤的种子密度显著高于下层.旱田以夏熟和秋熟杂草为主,而水田则以水田和夏熟杂草为主.按形态类型划分,水田及旱田中杂草种类数和密度从大到小均依次排序为阔叶草类、禾草类、莎草类,且水田中这3类杂草的种类数和种子密度均高于旱田.与旱田相比,水田杂草种子库的物种丰富度指数(S)、Shannon-Wiener 指数(H')和Simpson指数(D)较高,但Pielou均匀度指数(E)较低;旱田杂草种子库的S、H'

  4. Canine and human visual cortex intact and responsive despite early retinal blindness from RPE65 mutation.

    Directory of Open Access Journals (Sweden)

    Geoffrey K Aguirre


    Full Text Available BACKGROUND: RPE65 is an essential molecule in the retinoid-visual cycle, and RPE65 gene mutations cause the congenital human blindness known as Leber congenital amaurosis (LCA. Somatic gene therapy delivered to the retina of blind dogs with an RPE65 mutation dramatically restores retinal physiology and has sparked international interest in human treatment trials for this incurable disease. An unanswered question is how the visual cortex responds after prolonged sensory deprivation from retinal dysfunction. We therefore studied the cortex of RPE65-mutant dogs before and after retinal gene therapy. Then, we inquired whether there is visual pathway integrity and responsivity in adult humans with LCA due to RPE65 mutations (RPE65-LCA. METHODS AND FINDINGS: RPE65-mutant dogs were studied with fMRI. Prior to therapy, retinal and subcortical responses to light were markedly diminished, and there were minimal cortical responses within the primary visual areas of the lateral gyrus (activation amplitude mean +/- standard deviation [SD] = 0.07% +/- 0.06% and volume = 1.3 +/- 0.6 cm(3. Following therapy, retinal and subcortical response restoration was accompanied by increased amplitude (0.18% +/- 0.06% and volume (8.2 +/- 0.8 cm(3 of activation within the lateral gyrus (p < 0.005 for both. Cortical recovery occurred rapidly (within a month of treatment and was persistent (as long as 2.5 y after treatment. Recovery was present even when treatment was provided as late as 1-4 y of age. Human RPE65-LCA patients (ages 18-23 y were studied with structural magnetic resonance imaging. Optic nerve diameter (3.2 +/- 0.5 mm was within the normal range (3.2 +/- 0.3 mm, and occipital cortical white matter density as judged by voxel-based morphometry was slightly but significantly altered (1.3 SD below control average, p = 0.005. Functional magnetic resonance imaging in human RPE65-LCA patients revealed cortical responses with a markedly diminished activation volume (8

  5. 厌食症合并窦性心动过缓1例%Anorexia with sinus bradycardia:a case report

    Institute of Scientific and Technical Information of China (English)

    王方芳; 徐玲; 陈宝霞; 崔鸣; 张媛


    SUMMARY Asanorexiapatientsalwaysgotothepsychiatricclinic,littleisconcernedabouttheoccur-rence of sinus bradycardia in these patients for cardiologists and psychiatrists.The aim of this paper is to discuss the relationship between anorexia and sinus bradycardia,and the feature analysis,differential diagnosis and therapeutic principles of this type of sinus bradycardia.We report a case of sinus bradycar-dia in an anorexia patient with the clinical manifestations,laboratory exams,auxiliary exams,therapeutic methods,and her prognosis,who was admitted to Peking University Third Hospital recently.The patient was a 1 9-year-old female,who had the manifestation of anorexia.She lost obvious weight in a short time (about 1 5 kg in 6 months),and her body mass index was 1 4.8 kg/m2 .The patient felt apparent palpi-tation,chest depression and short breath,without dizziness,amaurosis or unconsciousness.Vitals on presentation were notable for hypotension,and bradycardia.The initial exam was significant for emacia-tion,but without lethargy or lower extremity edema.The electrocardiogram showed sinus bradycardia with her heart rate being 32 beats per minute.The laboratory work-up revealed her normal blood routine,elec-trolytes and liver function.But in her thyroid function test,the free thyroid (FT)hormones 3 was 0.91 ng/L (2.3-4.2 ng/L),and FT4 was 8.2 ng/L(8.9 -1 8.0 ng/L),which were all lower;yet the thy-roid stimulating hormone(TSH)was normal 1 .48 IU/mL(0.55 -4.78 IU/mL).Ultrasound revealed her normal thyroid.Anorexia is an eating disorder characterized by extremely low body weight,fear of gaining weight or distorted perception of body image,and amenorrhea.Anorexia patients who lose weight appa-rently in short time enhance the excitability of the parasympathetic nerve,and inhibit the sympathetic nerve which lead to the appearance of sinus bradycardia,and functional abnormalities of multiple systems such as hypothyroidism.But this kind of sinus bradycardia and hypothyroidism

  6. Delivering Transgenic DNA Exceeding the Carrying Capacity of AAV Vectors. (United States)

    Hirsch, Matthew L; Wolf, Sonya J; Samulski, R J


    Gene delivery using recombinant adeno-associated virus (rAAV) has emerged to the forefront demonstrating safe and effective phenotypic correction of diverse diseases including hemophilia B and Leber's congenital amaurosis. In addition to rAAV's high efficiency of transduction and the capacity for long-term transgene expression, the safety profile of rAAV remains unsoiled in humans with no deleterious vector-related consequences observed thus far. Despite these favorable attributes, rAAV vectors have a major disadvantage preventing widespread therapeutic applications; as the AAV capsid is the smallest described to date, it cannot package "large" genomes. Currently, the packaging capacity of rAAV has yet to be definitively defined but is approximately 5 kb, which has served as a limitation for large gene transfer. There are two main approaches that have been developed to overcome this limitation, split AAV vectors, and fragment AAV (fAAV) genome reassembly (Hirsch et al., Mol Ther 18(1):6-8, 2010). Split rAAV vector applications were developed based upon the finding that rAAV genomes naturally concatemerize in the cell post-transduction and are substrates for enhanced homologous recombination (HR) (Hirsch et al., Mol Ther 18(1):6-8, 2010; Duan et al., J Virol 73(1):161-169, 1999; Duan et al., J Virol 72(11):8568-8577, 1998; Duan et al., Mol Ther 4(4):383-391, 2001; Halbert et al., Nat Biotechnol 20(7):697-701, 2002). This method involves "splitting" the large transgene into two separate vectors and upon co-transduction, intracellular large gene reconstruction via vector genome concatemerization occurs via HR or nonhomologous end joining (NHEJ). Within the split rAAV approaches there currently exist three strategies: overlapping, trans-splicing, and hybrid trans-splicing (Duan et al., Mol Ther 4(4):383-391, 2001; Halbert et al., Nat Biotechnol 20(7):697-701, 2002; Ghosh et al., Mol Ther 16(1):124-130, 2008; Ghosh et al., Mol Ther 15(4):750-755, 2007). The other major

  7. 眼部疾病的基因治疗进展%Advance in gene therapy of ocular disease

    Institute of Scientific and Technical Information of China (English)



    目前,全世界已有31项眼部疾病基因治疗临床试验被批准,多数仍处于研究阶段.Leber先天性黑朦(LCA)目前已开展Ⅲ期临床试验,随访时间最长6年;无脉络膜症多中心的临床试验也取得了积极效果;视网膜色素变性(RP)已开展基因治疗Ⅰ期临床试验;年龄相关性黄斑变性(AMD)基因治疗的Ⅰ期临床试验结果令人鼓舞;青光眼基因治疗中使用RNA干扰技术和优化的偶联表面活性磷脂纳米微粒也取得了良好效果.就LCA、RP、无脉络膜症、AMD和青光眼基因治疗的一些实验室及临床研究进展,包括眼部基因治疗方法、各种基因载体和常用的动物模型等进行综述.病毒载体已广泛应用于眼部疾病的基因治疗中,一些与免疫排斥和基因突变相关的潜在性风险以及个体反应的差异性促使人们去探索更安全、高效的方法.基因编辑技术的出现,必将对眼部疾病的基因治疗领域产生深远影响.%Currently,31 clinical trials have been approved,most of them are still in progress.Leber congenital amaurosis (LCA) has been conducted to phase Ⅲ clinical trials,the longest follow-up time was 6 years.A multicenter clinical trial about choroideremia has achieved positive effect.Retinitis pigmmentosa (RP) has been conducted to phase Ⅰ clinical trials.Gene therapy for phase Ⅰ clinical trials of age-related macular degeneration (AMD) have achieved encouraging results.RNA interference and optimized gemini surfactant-phospholipid nanoparticles(GL-NPs) have been applied to gene therapy for glaucoma and have achieved good effects.In this paper,laboratory and clinical research progress of gene therapy of LCA,RP,choroideremia and AMD,glaucoma are reviewed,including gene therapy drug delivery methods,gene carrier and common animal models,etc.Viral vectors have been widely used,the potential risk associated with immunogenicity and mutagenesis,the differences of individual reaction have promoted

  8. Distrofias retinianas da infância: análise retrospectiva Retinal dystrophies in childhood: retrospective analysis

    Directory of Open Access Journals (Sweden)

    Heloisa Andrade Maestrini


    distrofias retinianas da infância são um grupo heterogêneo de doenças que se manifestam por meio de sintomas inespecíficos. Uma análise cuidadosa dos sintomas, o exame oftalmológico completo e os exames complementares, principalmente ERG, testes de visão de cores e campo visual, podem ser úteis em seu diagnóstico.PURPOSE: To describe the clinical features and the results of diagnostic methods in all patients with diagnosis of one of the following retinal dystrophies: Leber congenital amaurosis (LCA, achromatopsia, cone distrophy or cone-rod distrophy, examined at the Low Vision Department of the Federal University of Minas Gerais, in the period of 1992 to 2003. METHODS: Retrospective analysis of charts of 40 patients. Ten had LCA, 17 had achromatopsia, 6 had cone distrophy and 7 had cone-rod distrophy. RESULTS: Visual acuity was extremely low in patients with LCA, ranging from 20/710 to light perception. The mean value for achromatopsia was 20/200, 20/280 for cone distrophy and 20/260 for cone-rod distrophy. High hyperopia was the most common refractional error in LCA patients. Hyperopia was more frequent in cases of achromatopsia and cone distrophy, while in cone-rod distrophy myopia predominated. Fundoscopy was altered in most cases of LCA, cone distrophy and rod-cone distrophy, and normal in most cases of achromatopsia. Oculodigital sign and enophtalmus were found only in LCA patients while photofobia and color vision defects prevailed in other groups. Nistagmus and strabismus were frequent findings in all groups. There was a high incidence of delayed neuro-psycho-motor development in LCA patients. Two of them had also associated genetic syndromes. Patients presented symptoms very early in life in LCA and achromatopsia, while in cone and cone-rod distrophies symptoms appeared later, but never after the age of 10. Consanguinity and positive familial history were strongly associated in all groups. The ERG was extinct in LCA, showed reduced photopic response in

  9. Delivering Transgenic DNA Exceeding the Carrying Capacity of AAV Vectors (United States)

    Hirsch, Matthew L.; Wolf, Sonya J.; Samulski, R.J.


    Gene delivery using recombinant adeno-associated virus (rAAV) has emerged to the forefront demonstrating safe and effective phenotypic correction of diverse diseases including hemophilia B and Leber’s congenital amaurosis. In addition to rAAV’s high efficiency of transduction and the capacity for long-term transgene expression, the safety profile of rAAV remains unsoiled in humans with no deleterious vector-related consequences observed thus far. Despite these favorable attributes, rAAV vectors have a major disadvantage preventing widespread therapeutic applications; as the AAV capsid is the smallest described to date, it cannot package “large” genomes. Currently, the packaging capacity of rAAV has yet to be definitively defined but is approximately 5 kb, which has served as a limitation for large gene transfer. There are two main approaches that have been developed to overcome this limitation, split AAV vectors, and fragment AAV (fAAV) genome reassembly (Hirsch et al., Mol Ther 18(1):6–8, 2010). Split rAAV vector applications were developed based upon the finding that rAAV genomes naturally concatemerize in the cell post-transduction and are substrates for enhanced homologous recombination (HR) (Hirsch et al., Mol Ther 18(1):6–8, 2010; Duan et al., J Virol 73(1):161–169, 1999; Duan et al., J Virol 72(11):8568–8577, 1998; Duan et al., Mol Ther 4(4):383–391, 2001; Halbert et al., Nat Biotechnol 20(7):697–701, 2002). This method involves “splitting” the large transgene into two separate vectors and upon co-transduction, intracellular large gene reconstruction via vector genome concatemerization occurs via HR or nonhomologous end joining (NHEJ). Within the split rAAV approaches there currently exist three strategies: overlapping, trans-splicing, and hybrid trans-splicing (Duan et al., Mol Ther 4(4):383–391, 2001; Halbert et al., Nat Biotechnol 20(7):697–701, 2002; Ghosh et al., Mol Ther 16(1):124–130, 2008; Ghosh et al., Mol Ther 15

  10. Occipitotemporal epilepsies: clinical characteristics and the role of diagnostic modalities%颞-枕叶交界区癫痫的致痫区定位研究

    Institute of Scientific and Technical Information of China (English)

    吴英; 陈述花; 张玮; 刘兴洲; 栾国明


    .Excellent results were shown in three patients while two patients showed poor results.The other two remaining patients from the 7 cases were diagnosed with occipitoemporal epilepsy and did not undergo surgical treatment because of financial reasons.None of the patients experienced elementary visual hallucinations and ictal blurred vision or amaurosis during the monitored time.However,rapid eye blinking,as an initial seizure manifestation with or without aura,was observed in six patients.Scalp interictal and ictal discharges are frequently abnormal.Diffused or bilateral distribution of interictal spikes was observed in 4 out of the 7 patients and unilateral in 2 of the patients.Scalp interictal discharges is located in the right temporal areas in 1 out of the 7 patients.In 5 of the patients,the distribution of seizures,measured with the scalp EEG,were either multilobar,the entire hemisphere,or were generalized at onset.In the other 2 patients,seizures were located in the posterior areas in one patient and in the right temporal areas in the other patient.Conclusions Scalp interictal and ictal EEG changes were unreliable markers of Occipitotemporals' origin of seizure activity.Initial symptoms and signs and Head MRIs may be crucial clues in indicating the epileptoginic zone of occipitotemporal epilepsy.