bluuebunny/crossref_metadata_2025 huggingface dataset:
Colchicine Revisited
Authors: Bhat Anupama , Naguwa Stanley M. , Cheema Gurtej S. , Gershwin M. Eric
Published: September 2009

Purified from a Mediterranean plant nearly two centuries ago, colchicine has been discovered to inhibit many steps in the inflammatory process. The drug has good oral bioavailability and some enterohepatic recirculation, requiring dose adjustments for kidney disease and avoidance in liver disease. Toxicities are primarily gastrointestinal, hepatic, and hematologic. Colchicine is approved by the U.S. Federal Drug Administration for the treatment and prophylaxis of gout flares but has also been tried with varying success in the treatment of familial Mediterranean fever, primary biliary cirrhosis, psoriasis, Behçet's disease, aphthous stomatitis, linear IgA dermatosis, relapsing polychondritis, Sweet's syndrome, scleroderma, amyloidosis, leukocytoclastic vasculitis, epidermolysis bullosa, and dermatomyositis.
Race Differences in Immunogenetic Features and Photosensitivity of Cutaneous Lupus Erythematosus from the Aspect of Japanese Studies
Authors: Furukawa Fukumi , Yamamoto Yuki , Kanazawa Nobuo , Muto Masahiko
Published: September 2009

Skin lesions of collagen diseases are influenced by environmental triggers, such as UV light, and are variable in cutaneous lupus erythematosus (LE), such as systemic LE (SLE), chronic discoid LE (CDLE), subacute cutaneous LE (SCLE), and LE tumidus (LET). Although there are a few conflicting reports on photosensitivity in collagen diseases, many Japanese dermatologists feel there are photosensitivity differences in LE between Asians and Caucasians with SCLE and LET. To address this issue, we have carried out genetic studies of Japanese SLE and CDLE patients and reviewed the race differences in photosensitivity of cutaneous LE from Japanese studies. Human leukocyte antigen (HLA) studies in Japanese patients revealed that HLA‐DRB1*1501 association was with CDLE and SLE. The association between HLA‐Cw6 and CDLE was first reported in a Japanese population, and a HLA‐A33‐B44‐DRB1 * 1302 haplotype showed a positive association in CDLE. However, these results are not compatible with those from Caucasian subjects. There are no significant associations among HLA studies, photosensitivity, and anti‐Ro/SS‐A antibodies in Japanese CLE patients. Photosensitivity will be a key factor to dissolve multifactorial complexes of LE etiopathogenesis. An axis of photosensitivity, anti‐Ro/SS‐A antibodies, and apoptosis via tumor necrosis factor‐α is the best marker to verify the contribution of genetics in CLE patients. The incidence and degree of photosensitivity of SCLE and LET are much lower in Japanese than in Caucasians. This discrepancy may lead to investigations of CLE pathogenesis through global collaborations.
Role for CaMKII Inhibition in Rheumatoid Arthritis
Authors: Westra Johanna , Brouwer Elisabeth , Bouwman Erwin , Doornbos‐van der Meer Berber , Posthumus Marcel D. , Van Leeuwen Miek A. , Limburg Pieter C. , Ueda Yutaka , Kallenberg Cees G.M.
Published: September 2009

Background and aims: The present study was designed to investigate the effects of a novel CaMKII inhibitor SMP‐114, which was effective in a collagen‐induced arthritis model in rats, on rheumatoid synovial fibroblasts. Methods: Rheumatoid synovial fibroblasts (RSF) were cultured under pro‐inflammatory (IL‐1β stimulation) and hypoxic conditions. Protein and mRNA expression of HIF‐1α and the effects of inhibitors of the CaMKII‐, PI3K‐, and ERK pathway on VEGF and IL‐6 production were analyzed. Results: Stimulation under hypoxic conditions induced higher expression of HIF‐1α and VEGF mRNA than treatment with either IL‐1β or hypoxia alone. However, incubation with a specific CaMKII inhibitor did not result in reduced VEGF production in RSF. Conclusions: CaMKII activation has been reported to be involved in HIF‐1α stabilization, but incubation with SMP‐114, a specific CaMKII inhibitor, had no effect on HIF‐1‐induced VEGF production by rheumatoid synovial fibroblasts.
Autoantibodies, Polymorphisms in the Serotonin Pathway, and Human Leukocyte Antigen Class II Alleles in Chronic Fatigue Syndrome
Authors: Ortega‐Hernandez Oscar‐Danilo , Cuccia Mariaclara , Bozzini Sara , Bassi Nicola , Moscavitch Samuel , Diaz‐Gallo Lina‐Marcela , Blank Miri , Agmon‐Levin Nancy , Shoenfeld Yehuda
Published: September 2009

This study aimed to determine the influence of autoantibodies, polymorphisms in the serotonin pathway, and human leukocyte antigen (HLA) class II genes on age at chronic fatigue syndrome (CFS) onset and symptoms. Eighty‐one CFS patients were enrolled, and clinical data were recorded. Autoantibodies to different components of the central nervous system were tested. Polymorphisms in the promoter of the serotonin transporter gene (l/s) and a single nucleotide polymorphism in the serotonin receptor‐2A gene (A/G) as well as HLA class II alleles were determined. Multivariate logistic‐regression analyses were carried out. The mean age at CFS onset ± SD was 33.5 ± 12.5 years. An age at CFS onset (ACFSO) during the third decade of life was associated with the serotonin receptor AA genotype and the HLA‐DRB1*03 allele. An ACFSO during the fourth decade of life was associated with the HLA‐DRB1*07 allele, whereas an ACFSO ≥ 43 years was associated with having at least one copy of the serotonin G allele. Concerning CFS symptoms, the serotonin AG genotype was protective against depressive symptoms. Although having at least one copy of the serotonin A allele and being female were associated with risk for arthralgia, the presence of antineuronal cell antibodies was protective against this. Episodes of unexplained fever were associated with the HLA‐DRB1*11 allele. None of the genetic or serological features was associated with myalgia. None of the antibodies determined correlated with any ACFSO or other symptoms. Our results reveal that in CFS, like other autoimmune diseases, different genetic features are related to age at CFS onset and symptoms.
Oversecretion of Cytokines and Chemokines in Lupus Nephritis Is Regulated by Intraparenchymal Dendritic Cells
Authors: Tucci Marco , Ciavarella Sabino , Strippoli Sabino , Dammacco Franco , Silvestris Franco
Published: September 2009

Lupus nephritis (LN) occurs in more than one‐third of patients with systemic lupus erythematosus. Its pathogenesis is attributed to the glomerular deposition of immune complexes as well as to imbalance of the cytokine homeostasis. In this context, high production of cytokines and chemokines by dendritic cells (DCs) may concur to LN. In addition, urinary cytokine excretion may reflect the accumulation of DCs within glomeruli. DCs are differentiated in both myeloid and plasmacytoid (p) subsets in relation to their typical antigen and chemokine expression. Both subsets migrate in response to chemotactic stimuli because pDCs are susceptible to IL‐18 expressed by resident glomerular cells. pDCs bear the IL‐18R, and it is conceivable that DCs migrate to the kidney under the attraction of IL‐18. Therefore, the depletion of DCs reflects the inflammation severity in LN, whereas measurement of Th1 cytokines may represent an effective tool for monitoring the onset of LN.
Cardiovascular Nursing on Human Genomics: What Do Cardiovascular Nurses Need to Know About Congestive Heart Failure?
Authors: Frazier Lorraine , Wung Shu‐Fen , Sparks Elizabeth , Eastwood Cathy
Published: September 2009

This paper presents the main causes of heart failure (HF) and an update on the genetics studies on each cause. The review includes a delineation of the etiology and fundamental pathophysiology of HF and provides rational for treatment for the patient and family. Various cardiomyopathies are discussed, including primary cardiomyopathies, mixed cardiomyopathies, cardiomyopathies that involve altered cardiac muscle along with generalized multiorgan disorders, and various cardiovascular conditions, such as coronary artery disease (ischemic cardiomyopathy) and hypertension (hypertensive cardiomyopathy). A brief review of pharmacogenetics and HF is presented. The application of the genetic components of cardiomyopathy and pharmacogenetics is included to enhance cardiovascular nursing care.
The Lived Experience of Middle‐Aged Women with New York Heart Association Class III Heart Failure: A Pilot Study
Authors: Allen Jennifer Wayment , Arslanian‐Engoren Cynthia , Lynch‐Sauer Judith
Published: September 2009

Although heart failure (HF) is equally prevalent in men and women, women with HF are more likely to report decreased quality of life and are more likely to die of the disease compared with men. Moreover, HF has been studied less extensively in women and no study has specifically addressed women with New York Heart Association (NYHA) class III HF using a qualitative method. This pilot study sought to gain insight into the lived experience of women with NYHA class III HF. Using a phenomenological approach, interviews obtained from 4 middle‐aged women with NYHA class III HF were analyzed using the Giorgi method of data analysis. Five themes emerged: (1) developing a new conception of self, (2) conceding physical limitations, (3) enduring emotional heartache, (4) accepting support, and (5) rejuvenating through rest. This study provides a beginning to our understanding of the lived experience of women with NYHA class III HF. However, further exploration is needed to increase our knowledge of HF in women, particularly among diverse populations.
Les risques politiques et la privatisation du système de retraite: le cas de l'Argentine (1994‐2008)
Authors: Kay Stephen J.
Published: September 2009

Les tenants de la privatisation des retraites en Amérique latine ont soutenu que les régimes privés par capitalisation anticipée à cotisations définies fondés sur des comptes individuels seraient mieux à l'abri de la politique que les régimes publics par répartition. Cependant, comme l'illustre le cas argentin, et plus récemment avec la nationalisation en 2008 de son système privé de comptes individuels, le transfert de la gestion et de la capitalisation des pensions au secteur privé n'a pas nécessairement réduit ni éliminé le risque politique. En fait, la mise en œuvre des régimes de comptes individuels crée une nouvelle série de risques politiques, en partie parce qu'ils constituent une ressource financière potentielle pour les gouvernements, surtout en périodes de difficultés économiques. Le présent article décrit l'éventail de risques politiques inhérents aux régimes de retraite fondés sur des comptes individuels, en mettant l'accent sur l'expérience de privatisation en Argentine pendant la période de 1994‐2008.
Affiliation volontaire au régime de retraite à comptes individuels du Pérou
Authors: Li Carmen A. , Olivera Javier
Published: September 2009

Un aspect important de la conception de la protection sociale est la couverture. Au Pérou, comme dans la plupart des pays latino‐américains, la couverture de la sécurité sociale n'est obligatoire que pour les travailleurs du secteur formel. Les auteurs du présent article ont étudié les déterminants de l'affiliation volontaire au régime de retraite à comptes individuels du Pérou. Ils ont constaté qu'un groupe de population bien précis a davantage de chances de s'affilier volontairement que d'autres personnes. Ce groupe est composé d'hommes mariés ayant un niveau d'éducation supérieur à celui de l'enseignement secondaire et vivant dans des ménages à hauts revenus dont d'autres membres sont déjà affiliés à un régime de retraite à comptes individuels. Pour le reste, les résultats obtenus laissent à penser que les filets de sécurité basés sur la famille peuvent servir de solution de remplacement à la participation volontaire au régime de retraite à comptes individuels. Il n'en demeure pas moins que l'extension de la couverture des pensions et la lutte contre la pauvreté restent problématiques pour le gouvernement.
Freiwillige Verbesserung der sozialen Sicherheit: Aktuelle gesetzliche Regelung und Rechtsprechung in Spanien
Authors: García Valverde María Dolores , García Valverde Francisco
Published: September 2009

Auszug

Mit der vorliegenden Arbeit soll dem Leser eine Übersicht über freiwillige Beiträge zur Verbesserung von Sozialleistungen (mejoras voluntarias) als Form der freiwilligen Sozialvorsorge des spanischen Systems der sozialen Sicherheit geboten werden. Um dieses Ziel zu erreichen, haben wir die verschiedenen Modalitäten dieser freiwilligen Verbesserungen analysiert, unter Gesichtspunkten der gesetzlichen Regelung und der Rechtsprechung. Besonders berücksichtigt wurden konfliktträchtige Probleme. Die freiwilligen Verbesserungen sollten zwar Privatinitiativen im Bereich der sozialen Vorsorge fördern, sie verbleiben jedoch in der Obhut der sozialen Sicherheit, die die Kontrolle sowohl über die Finanzierung als auch über die Verfahren behält. Wie in der Arbeitswelt üblich, unterliegt ihre Gestaltung kollektiven Tarifverhandlungen.
El seguro de dependencia en el Japón: superación de la visión binaria entre el Estado y la familia
Authors: Naïto Kusuto
Published: September 2009

La atención de la salud de las personas de edad avanzada dependientes ha sido considerada en el Japón como una actividad que incumbe exclusivamente a la esfera familiar, a pesar de que, por un lado, existe una gran diversidad regional en términos de estructuras familiares y de que, por otro lado, en el pasado existían simultáneamente solidaridades extrafamiliares. La evolución sociodemográfica desde mediados del siglo XX ha conducido a los poderes políticos, pero también a la opinión pública, a crear un seguro público de dependencia, establecido en 2000 y encaminado a «socializar» esas actividades que, en principio, eran familiares y femeninas. Este artículo propone un análisis crítico del sistema y del contexto en que se generó el seguro. ¿Responde el sistema a las necesidades de las personas de edad avanzada y de sus entornos (familiares y no familiares)? Además, ¿tiene en cuenta las diversidades regionales, en particular en lo relativo a la situación de las familias, además de los problemas financieros y de las presunciones sociales? El proceso de envejecimiento demográfico que experimentan las sociedades industrializadas nos obliga a revisar los avances histórico‐sociales de esas sociedades, con el fin de adaptar regularmente los comportamientos y lugares de residencia a los contextos socioeconómicos que evolucionan rápidamente.
Las mejoras voluntarias de la seguridad social: situación actual en la normativa y la jurisprudencia de España
Authors: García Valverde María Dolores , García Valverde Francisco
Published: September 2009

Con este trabajo se pretende ofrecer al lector una visión general sobre las mejoras voluntarias como forma de previsión social voluntaria del sistema español de Seguridad Social. Para conseguir este objetivo hemos analizado las distintas modalidades de mejoras voluntarias, tanto desde el punto de vista legal como de la jurisprudencia. Dedicando una especial atención a los principales problemas que son objeto de conflicto. Con las mejoras voluntarias se pretendía fomentar la iniciativa privada en materia de previsión social, pero encauzándola hacia la Seguridad Social, como medio de control tanto de fondo, cuanto de procedimiento. Junto a la práctica empresarial, su articulación se vincula a la negociación colectiva.
Are Debt and Incentive Compensation Substitutes in Controlling the Free Cash Flow Agency Problem?
Authors: Zhang Yilei
Published: September 2009

This paper investigates the governance implications of a firm's capital structure and managerial incentive compensation in controlling the free cash flow agency problem. The results suggest: debt and executive stock options act as substitutes in attenuating a firm's free cash flow problem; failure to incorporate the substitutability and endogeneity leads to underestimates of the magnitude and economic implication of the disciplinary role of both mechanisms; firm characteristics differ across the prevalence of debt usage versus option usage, suggesting the heterogeneity in the costs and benefits of the monitoring devices; and all the above effects are more pronounced in firms that tend to have more severe agency problem.
Local Effects of Foreign Ownership in an Emerging Financial Market: Evidence from Qualified Foreign Institutional Investors in Taiwan
Authors: Huang Roger D. , Shiu Cheng‐Yi
Published: September 2009

We examine the local effects of equity ownership by investors who are classified as qualified foreign institutional investors in Taiwan. Our empirical analyses reveal a pronounced foreign ownership effect, whereby stocks with high foreign ownership outperform stocks with low foreign ownership. The valuation effect is present even after controlling for firm export, size, or transparency levels. We pursue a performance‐based explanation for this effect and find that foreign ownership is strongly and positively associated with firm R&D expenditures and contemporaneous and subsequent firm performance. Our evidence is consistent with foreign investors who enjoy a long‐run information advantage over domestic investors.
Derivatives Use, Information Asymmetry, and MNC Post‐Acquisition Performance
Authors: Lin J. Barry , Pantzalis Christos , Park Jung Chul
Published: September 2009

We utilize a sample of US acquiring firms that engaged in international M&As to document the effects of corporate derivatives use on post‐M&A long‐term performance. We find that derivatives users outperform nonusers. Furthermore, we find that acquirers with derivative policies that are more comprehensive and sophisticated outperform those with less comprehensive and sophisticated policies. They, in turn, outperform acquirers with no existing policies in place. Our results are consistent with the notion that the use of derivatives lowers information asymmetry related agency problems. Furthermore, our evidence indicates that derivatives use is an important corporate activity that has a profound effect on post‐M&A performance.
Immunosuppression in children (JIA)
Authors: BODAGHI B
Published: September 2009

Abstract not provided
Infliximab (Remicade?) in uveitis: a review
Authors: ABU EL ASRAR A , NERI P , HERBORT CP
Published: September 2009

Tumor necrosis factor (TNF)‐α has been implicated as an important mediator in autoimmune ocular inflammatory disease pathogenesis as shown by animal studies and its detection in the ocular fluids of patients with uveitis. Blockade of TNF‐α has emerged as one of the most promising therapies in autoimmune diseases including uveitis. Currently, there are three TNF‐α antagonists: two monoclonal antibodies (infliximab and adalimumab) and a soluble receptor that binds soluble TNF‐α (etanercept). Infliximab is a chimeric monoclonal antibody directed against TNF‐α. It binds with high affinity to both the soluble and the membrane‐bound TNF‐α and inhibits a broad range of biologic activities of TNF‐α. Binding to membrane TNF‐α can mediate programmed cell death. Several studies reported that infliximab therapy was rapidly effective and safe treatment for refractory noninfectious uveitis including childhood uveitis and is indicated as rescue therapy for relapses of ocular inflammation or as maintenance therapy when conventional immunosuppression fails. It also allowed a reduction of corticosteroids and immunosuppressive drugs required to control the disease. However, repeated infusions are required to maintain long‐term remission. Moreover, infliximab administration is costly and requires hospital admission. Adalimumab, fully humanized monoclonal anti‐ TNF‐α antibody, was also found to be effective and safe therapy for the management of refractory noninfectious uveitis. Several studies reported that infliximab was more effective than etanercept in the treatment of refractory uveitis. Perhaps infliximab’s ability to target membrane‐bound TNF‐α in addition to the soluble form may contribute to its increased efficacy in comparison with etanercept for uveitis.
What do I need to improve my glaucoma skills?
Authors: BRON AM
Published: September 2009

Purpose Many new devices and technologies are available nowadays in the diagnosis and the treatment of glaucomas. However for young practitioners, it is mandatory to concentrate on symptoms and clinical signs.

Methods In this presentation I will assess the place of the clinical examination in the overall management of glaucoma.In clinical practice many clues for glaucoma are found with simple instruments; a slit‐lamp, a gonio‐lens and a fundus lens. I will provide a frame, a sort of check list in order to build a diagnosis with the signs found during the clinical examination.

Conclusion A moderate knowledge about ocular anatomy and physiology will lead the young resident through an easier diagnosis of glaucoma.Looking for the relevant symptoms and signs during the clinical examination will lead the young practitioner to a good accuracy in the diagnosis of glaucoma.
Parasitic corneal infections
Authors: GICQUEL JJ
Published: September 2009

The exposure of the eye directly to the environment renders it vulnerable to a number of uncommon infectious diseases caused by parasites. Once anatomical barriers are breached, host defences are often insufficient to prevent the infection from spreading localy. A fast identification and treatment of the involved microorganisms are necessary. Contact lens wear is associated with keratitis caused Acanthamoebae. Parasitic infections may also arise following bloodborne carriage of the microorganism to the eye or adjacent structures.
Diagnosis of ophthalmic tumours
Authors: KIVELÄ T
Published: September 2009

Purpose To summarise clinical methods used to diagnose ophthalmic tumours.

Methods Personal experience of the author as a member of the European Ophthalmic Oncology Group.

Results Conjunctival tumours are excised based on provisional clinical diagnosis or, if they are extensive, atypical or part of systemic disease such as lymphoma, first biopsied to obtain a histopathologic diagnosis. Useful methods to diagnose and stage conjunctival tumours are high frequency ultrasonography (US) or ultrasound biomicroscopy (UBM) to measure their thickness, in vivo confocal microscopy or impression cytology to chart their extent, and exfoliative cytology to get a provisional diagnosis. Ciliary body tumours are visualised by radical biomicroscopy, transillumination and indirect ophthalmoscopy with scleral indentation, supplemented with high frequency US or UBM. Binocular indirect ophthalmoscopy and US form the basis or diagnosing choroidal tumours. In addition to fluorescein and indocyanine green angiography in atypical cases, optical coherence tomography to detect subretinal fluid and autofluorescence to detect orange pigment are useful adjuncts in telling a small melanoma from a naevus. The mnemonic “To Find Small Ocular Melanomas” (from Thickness >2mm, subretinal Fluid, Symptoms, Orange pigment, Margin touching disc) is also useful in this respect. Clinical diagnosis of medium‐sized to large melanomas is 99% accurate, whereas a fine needle or vitrectomy biopsy may be necessary to diagnose atypical tumours and is also used for cytogenetic analysis of uveal melanomas.

Conclusion Conjunctival tumours are mostly diagnosed histopathologically, whereas diagnosis of uveal tumours is usually based on clinical examination. While clinical diagnosis is usually reliable, biopsy of uveal tumours is increasingly used for prognostic purposes.
Management of uveal tumours
Authors: DAMATO B
Published: September 2009

Purpose The purpose of this presentation is to describe the management of uveal melanomas and the other most common uveal tumours.

Methods Choroidal melanomas are treated with plaque radiotherapy if possible, with proton beam radiotherapy, stereotactic radiotherapy, trans‐scleral local resection, trans‐retinal endoresection, phototherapy and enucleation being reserved for patients who cannot be managed with a plaque. Increasingly, tumour biopsy is performed for histological grading of malignancy and for cytogenetic studies aimed at determining the genomic tumour type so that risk of metastatic disease can be determined. Choroidal metastases usually respond to external beam radiotherapy. Biopsy may be needed to confirm the diagnosis. Choroidal haemangiomas are treated by photodynamic therapy, with good response in most patients.

Results In the large majority of patients, it is possible to conserve the eye and vision. Patients need life‐long follow‐up in case tumour recurrence occurs. After radiotherapy of choroidal and ciliary body melanomas some patients develop exudative and neovascular complications needing treatment.

Conclusion Successful management of uveal tumours is based on a firm diagnosis, accurate staging of disease, reliable prognostication and adequate aftercare.
Treatment of ocular surface injuries by the transfer of limbal and mesenchymal stem cells growing on nanofibrous scaffolds
Authors: HOLAN V , ZAJICOVA A , LENCOVA A , POKORNA K , SVOBODOVA E , KRULOVA M
Published: September 2009

Purpose To use nanofibrous scaffolds to grow and transfer limbal stem cells (LSC) and mesenchymal stem cells (MSC) to treat ocular surface injuries in a mouse experimental model.

Methods Nanofibrous scaffolds were prepared by electrospinning procedure from a polyamid 6/12 (PA6/12). This polymer was selected on the basis of stability of nanofibres in aqueous solutions, biocompatibility and the best properties as a matrix for the growth of LSC and LSC. LSC and MSC labeled with a vital fluorescent dye PKH26 and grown on nanofibrous scaffold were transferred on the damaged eye surface, where their seeding and surviving were monitored. The effects of transferred cells on local inflammatory reactions were assessed by Real‐time PCR.

Results The morphology, growth properties and viability of LSC and MSC on PA6/12 nanofibres were comparable with those on plastic. Transfer of LSC and MSC growing on nanofibrous scaffolds on the damaged ocular surface significantly inhibited local inflammatory reactions and supported the healing process.

Conclusion The nanofibers prepared from polymer PA6/12 represent a convenient scaffold for LSC and MSC growth and transfer to treat SC deficiencies and various eye surface injuries.
Cell connections between lens fibres in the posterior pole of human and bovine lenses
Authors: VAN MARLE G , VRENSEN G , HOEBEN K
Published: September 2009

Purpose Gap junctions (GJs) between lens epithelial cells (LECs ) and between lens fibres (LFs) are prominent features of vertebrate lenses. However, they are absent between LECs and LFs. There is evidence for the presence of tight junctions (TJs) between LECs, and differentiating LFs but only in the equatorial pole. TJs are lacking between LFs. We are not aware of studies on cell‐to‐cell junctions in the posterior pole although its surface is about as large as that of the anterior surface. This study aimed to find morphological evidence for GJs & TJs in the posterior pole of bovine and human lenses using freeze fracture (FF) and thin section EM (TEM). It appeared that posterior LF membranes have a high density of intramembranous particles (IMPs). Broken necks of caveolae are sparse. Edge protrusions are often demarcated by single rows of IMPs. GJs are numerous on all LF membranes except on the outer, capsule facing, membranes. This suggests close coupling of posterior fibres. TJs proved to be totally lacking on all fibre membranes. TEM corroborated these findings, showing numerous GJs between posterior fibres. No evidence for TJs was found. However, numerous spot desmosomes were observed between the peripheral fibres.

Conclusion Lens fibres in the posterior pole are well coupled by GJs, but the presence of TJs could not be verified. The presence of spot desmosomes suggests a close mechanical attachment of posterior lens fibres. How the posterior pole regulates its solute transfer with the vitreous still remains to be elucidated.
Human anterior lens capsule epithelial cell contractions
Authors: ANDJELIC S , ZUPAN?I? G , PEROVšEK D , HAWLINA M
Published: September 2009

Purpose The transport over the lens epithelial cell layer is governed by different morphological parameters and junctions whose defects can lead to cataract formation. The cells are cuboidal, tightly packed with very little intercellular space. We studied their contractions due to agonist application.

Methods Entire anterior human capsules obtained from cataract surgery, with the cells still attached, were used. A good part of the cell contacts, including contacts to the basement membrane were preserved. To measure the [Ca2+]i and to monitor the cell morphology, the capsules were stained with the fluorescent dye Fura2. We applied either the agonist acetylcholine (ACh) solution or the physiological saline alone, to test whether the agonist is necessary to induce the cell contraction.

Results Lens epithelial cells in 23% (12/51) of the capsules contracted substantially upon ACh application and responded with an increase in [Ca2+]i. However, contraction also occurred, with very small increases in [Ca2+]i, when, as a control, physiological solution was applied in the same way, suggesting the possibility that the contraction can be induced mechanically.

Conclusion The major role of lens capsule epithelial cells is to be a regulating “barrier” between the aqueous humour and the lens fibre cells. The appearance of holes in this barrier, due to cell contraction, in response to not only agonist application but also presumably mechanical stimuli, compromises their basic function and may be a part of a pathophysiological mechanism associated with cataract formation.
Segmentation of FD‐OCT images shows selective loss of inner retinal layers in patients with DM and no or early DR
Authors: VERBRAAK FD
Published: September 2009

Purpose Determine whether diabetes differentially affects specific retinal layers by comparing the thickness of six retinal layers in diabetic patients with no or minimal diabetic retinopathy (DR) to age‐ and gender‐matched normal controls.

Methods Forty‐four patients with type 1 diabetes and no or minimal DR underwent full ophthalmic examination, stereoscopic fundus photographs and spectral domain optical coherence tomography (OCT). Following automated segmentation of intraretinal layers of the OCT images, mean thickness was calculated for 6 individual layers of the retina in the fovea, the pericentral area and the peripheral area of the central macula and compared to an age‐ and gender‐matched control group.

Results In type 1 diabetic patients with minimal DR, the retinal nerve fiber layer (p=0.00) and the ganglion cell/inner plexiform layer (p=0.02) were significantly thinner compared to age‐ and gender‐matched controls. No other layers showed a significant difference.

Conclusion Thinning of the total retina in diabetic patients with minimal DR relative to normal controls is due to a selective thinning of inner retinal layers and supports the concept that early DR includes a neuro‐degenerative component.
The human choroid posseses substance P and calcitonine gene‐related peptide intrinsic neurons
Authors: TRIVINO A , DE HOZ R , ROJAS B , SALAZAR JJ , RAMIREZ AI , GALLEGO B , RAMIREZ JM
Published: September 2009

Purpose To determine the presence of substance P (SP)‐and calcitonine gene‐related peptide (CGRP) positive intrinsic choroidal neurons (ICNs) in human

Methods Nineteen choroidal whole‐mounts were processed for indirect immunofluorescence. Antibody to a component of the neuronal cytoskeleton, neurofilament 200 kDa (NF‐200), was combined with antibodies to SP and to CGRP (neuropeptides proper to the sensory nervous system).

Results The human choroid possesses numerous SP(+) and CGRP(+) ICNs. These neurons were observed in the suprachoroid, both in isolation and forming microganglia. For both types of ICNs studied, neurons were more numerous in the temporal than in the nasal regions. In both locations, SP(+) and CGRP(+) ICNs were more abundant in the central choroid (the choroid underneath the macular area of the retina), with cell density diminishing outwards to the choroidal periphery. There were no appreciable differences between the two populations of ICNs studied in terms of size, morphology or immunostaining characteristics.

Conclusion The human choroid contains an abundant population of SP(+) and CGRP(+) ICNs. Given that peripheral sensory innervation could be involved in the regulation of both choroidal blood flow and vascular architecture, the SP(+) and CGRP(+) ICNs described for first time in the present work may be implicated in these mechanisms of vascular regulation
The effects of sub‐conjunctival EPO administration on ERG and on the peripheral blood haematocrit in animal model (rabbit)
Authors: DELGADO E , RESENDE AP , SAO‐BRAS B , DE SOUZA‐RAMALHO P
Published: September 2009

Purpose To assess the effects of subconjunctival EPO administration on retinal eletrophysiology and on the peripheral blood haematocrit.

Methods New Zealand White rabbits (n=6) received 100 UI of EPO through the subconjuntival route. Blood for Complete Blood Count (CBC) was collected on day 0, on day 7 and on day 14 of the experimental protocol. Furthermore electroretinograms were performed on day 0 and on day 30 of the experiments.

Results Regarding CBC changes, the haematocrit values changed from 35,42±2,7% on day 0 to 34,32±4,3% (p=0,390) on day 7 and to 34,45±4,4% on day 14 (p=0,931), showing no significant changes. Concerning the red blood cells (RBC x10000/µL) count, the values evolved from 6,02±0,48 on day 0 to 5,65±0,67 (p=0,074) on day 7 and to 5,67±0,74 (p=0,948) on day 14, showing no significant alterations. On the contrary, on what regards the electroretinograms, although there were no significant changes on a‐wave amplitudes, which evolved from 13,94±1,7 µV on day 0 to 13,67±0,8 µV on day 30 (p=0,844) and no significant differences on N1‐P1 amplitudes which changed from 46,60±4,5µV to 55,48±10,5 µV (p=0,438), there was a remarkable increase on b‐wave amplitude of 49%, changing from 46,60±7,43 µV to 94,97±13,36 µV (p=0,031).

Conclusion On what concerns CBC profiles, subconjuntival EPO administration did not cause any sinificant changes on haematocrit or RBC values. Regarding electrorretinography, there were no significant changes on a‐wave or N1‐P1 amplitudes, but there was a marked increase in the b‐wave amplitude which tests for photoreceptor functionality, which might indicate a protective action against apoptosis of retinal photoreceptors even in physiological conditions.
Tolerance and safety of ocular use of recombinant human erythropoietin (rhEPO). Neuroprotective effects in ocular hypertension/glaucoma
Authors: GOMES N , ROCHA DE SOUSA A , FALCAO REIS F , SONG BJ , DEL PRIORE LV
Published: September 2009

Purpose The purpose of this study was to evaluate the long‐term effects of monthly intravitreal injections of rhEPO in a rabbit model.

Methods Sixteen New Zealand rabbits were divided into 4 groups: control (no injection), saline injection, or rhEPO injections of 500 U and 1000 U (N=4 per group). The right eye of each animal was injected monthly over a period of 7 months. Fundus examination and electroretinography (ERG) were performed at 1 day prior, and 1 week, 1 month, and 6 months after the initial injection. After the final ERG, animals underwent fluorescein angiography and sacrifice one week later. Scotopic and photopic ERG amplitude and implicit times were analyzed by calculating a ratio between the right and the left eyes. Angiograms were graded for the presence of neovascularization or leakage. Statistical analysis was carried out using two‐way ANOVA.

Results Fifteen animals were used for this experiment (1 developed a traumatic cataract and was excluded). Between all groups and time points, there were no statistically significant differences in the computed right eye:left eye ratios for the scotopic or photopic ERG components (p>0.05). No evidence of neovascularization or fluorescein leakage was seen on angiography. There were no visible differences in retinal architecture or thickness in the rhEPO groups when compared to uninjected controls.

Conclusion Monthly 0.1 ml intravitreal injections of rhEPO at a dose of up to 1000 U over 7 months is well‐tolerated and does not cause adverse effects on retinal function, architecture, or vasculature in a rabbit model. A review of published data on rhEPO and Glaucoma will also be presented.
Intravitreal and plasmatic levels of erythropoietin after sub‐conjunctival administration in rabbits
Authors: RESENDE AP , DELGADO E , SAO‐BRAS B , DE SOUZA‐RAMALHO P
Published: September 2009

Purpose Recently Erythropoietin (EPO) had been shown to have neuroprotective and neuroregenerative effects on retinal ganglion cells, apart from its erythropoietic properties, being a promissory alternative on ischemic retinal diseases. With the present study we pretend to evaluate the efficacy of subconjuntival injection for ocular EPO delivery.

Methods New Zealand albino rabbits (n=6) were used. Complete ophthalmic examinations were carried out before and after the injections for 15 days. The proceedings (intravitreal punch and subconjuntival injections) were carried out under general anaesthesia. Through the subconjuntival route 100 UI of EPO diluted in 50 μl saline solution 0,9% was administered. The opposite eyes of each animal served as controls.The vitreous and plasmatic concentration of EPO were measured using the ELISA method.

Results Administration of EPO through the subconjuntival route allowed a vitreous absortion that reached the highest 24 hours after administration with 0,6 mUI/ml of EPO quantified in 100 μl of vitreous sample. The sistemic absorption reached the highest concentration 3 hours after subconjunctival administration and 48 hours after the administration the plasmatic concentration of EPO regained physiologic values. EPO was not detected on control eyes.

Conclusion All the previous studies used the systemic or intravitreal route of administration to acquire therapeutic concentrations of EPO on the retina, both difficult to use in clinical practice. In this study, the subconjuntival route proved to be a promising alternative for ocular EPO delivery. However further studies are necessary to assess the blood and intravitreal kinetics of EPO after subconjuntival administration.
Importance of electroretinogram in bull’s eye maculopathy
Authors: HALFELD FURTADO DE MENDONCA R , KOK F , ROSEMBERG S , YUKIHIKO TAKAHASHI W
Published: September 2009

Purpose To describe the retinographic, electroretinographic and ultra‐structural alteration in a interesting family case of bull’s eye maculopathy.

Methods A 14‐year‐old boy, his brother a 12‐year‐old boy and his sister a 10‐year‐old girl with visual loss, underwent complete ophthalmological exams, including retinography, electroretinography (ERG) and ultrastructural study by electron microscopy of the skeletal muscle, at the Clinical Hospital of the University of São Paulo.

Results All three children presented optic nerve pallor, arteriolar thinning and bull’s eye maculopathy. The scotopic responses were absent or with low amplitude contrasting with normal flicker responses. Electron microscopy study detected the curvilinear bodies typical from Neuronal Ceroid Lipofucinosis (NCL).

Conclusion The initial diagnose of those children was cone‐rod dystrophy. Diagnosis of NCL was established by normal ERG flicker and findings of characteristic electron microscopic curvilinear bodies. The electrophysiologic testing are very important in the early diagnosis of NCL.
Hunter's syndrome and buphthalmos in a girl: an unusual ophthalmic association
Authors: SETHI S , BHARTIYA S , MEHTA M , CHANDRA M , GHOSE S
Published: September 2009

Purpose To report an unusual ophthalmic presentation of a case of Hunter's syndrome/MPS II.

Methods A sixteen‐year‐old girl presented to us with total loss of vision and forward protrusion OU since early childhood. Detailed examination, including slit lamp biomicroscopy, Intra ocular pressure (IOP) and fundoscopy was carried out. Thorough systemic evaluation including Computed Tomography (CT), metabolic and genetic analysis was undertaken in collaboration with internists.

Results Characteristic facies, detection of glycosaminoglycan (GAG) variants in urine (chondroitin sulfate B and heparin sulfate) and iduronate‐2‐sulphatase activity in fibroblasts/leucocytes confirmed the diagnosis of MPS II. Child had severe photophobia but with no perception of light OU. OU buphthalmos with Haab's striae was noted, making a clear view of the fundus difficult. IOP OU was elevated, and 90D slit lamp biomicroscopy revealed a total glaucomatous optic atrophy in both eyes.On CT there was thickening and edema of preseptal and periorbital soft tissue with marked thinning of the optic nerves with prominent perineural CSF sleeves, indicative of marked optic atrophy.

Conclusion Glaucoma is a known association of Hurler's, Scheie's and Maroteaux‐Lamy syndromes but not Hunter's. In fact, there is only one report of suspected angle closure glaucoma in MPS II. Buphthalmos is not a likely presentation as the sclera in these patients is known to be thickened due to deposition of GAG. To the best of our knowledge, this is the first case report of buphthalmos in association with MPS II. The importance of a meticulous examination in this subset of patients cannot be overemphasised. An appropriate and timely intervention may result in a better quality of life for them.
Ocular rigidity in living human eyes in health and disease
Authors: PALLIKARIS IG
Published: September 2009

Purpose It is known that the balance between aqueous humor secretion and outflow rate controls the steady ‐ state average intraocular pressure (IOP). It has been also early identified that blood circulation results to IOP fluctuations practically synchronous to cardiac function. IOP is the primary mechanical load to several ocular structures including the optical nerve head.

Methods In‐vivo intraoperative measurement of these quantities as well as secretion/outflow coefficients in humans allowed us to quantify ocular rigidity, IOP and its fluctuations (and pulsatile blood flow) in a series of physiological and pathological eyes. Ocular rigidity, outflow facility and pulsatile ocular blood flow were measured intraoperatively in a cohort of 63 patients undergoing cataract surgery. Measurements were also performed in a series of age related macular degeneration (AMD) patients.

Results The eye, is a living structure under a continuously varying mechanical load that is strongly related to ocular haemodynamics. Ocular rigidity ranged from 0.0122 to 0.0343 (mean 0.0208)μl‐1. Outflow facility coefficient (derived from pressure decay curves) was 0.33 (sd 0.15)μl/min/mmHg. Pulsatile ocular blood flow exhibited a strong negative correlation to IOP in all subjects. The ocular rigidity coefficient was higher in wet AMD patients compared to patients with dry AMD and healthy controls.

Conclusion There are indications that this mechanical load, associated also to ocular rigidity, can not only inter‐modulate blood flow but also have a long‐term effect on other structures in the eye. Understanding the role of these parameters may contribute to the understanding of ocular disease.
Evidence for altered ocular rigidity in glaucoma
Authors: SCHMETTERER L , GARHOFER G
Published: September 2009

Purpose Based on theoretical models and animal studies altered biomechanical properties of the optic nerve head and the sclera have been implicated in the pathophysiology of glaucoma. Only few data have, however, demonstrated such biomechanical alterations in vivo. We tested the hypothesis that patients with primary open angle glaucoma (POAG) have an abnormal structural stiffness based on measurements of intraocular pressure amplitude and ocular fundus pulsation amplitude.

Methods Seventy patients with POAG and 70 healthy control subjects matched for age, gender, intraocular pressure and systemic blood pressure were included in this study. The ocular pulse amplitude (PA) was assessed with pneumotonometry. The fundus pulsation amplitude (FPA) was measured using laser interferometry. Based on the Friedenwald equation a coefficient of structural stiffness (E1) was calculated relating PA to FPA.

Results Systemic blood pressure, intraocular pressure, and ocular perfusion pressure was comparable between glaucoma patients and healthy control subjects. FPA as well as PA was lower in patients with glaucoma than in healthy controls. The calculated factor E1 was significantly higher in patients with POAG (0.0454 ± 0.0085 a.u.) than in healthy control subjects (0.0427 ± 0.0058 a.u., p = 0.03).

Conclusion This study is indicative of increased structural stiffness of the sclera in patients with POAG. This is in agreement with a number of previous animal experiments and supports the idea that the biomechanical properties of ocular tissues play a role in the process of glaucomatous ONH damage.
Ocular motor development in normal and premature children
Authors: YGGE J
Published: September 2009

The ocular motor system is immature at birth and the different types of eye movements develop at different stages of child development. This presentation aims to discuss the normal ocular motor development and the often delayed development of the ocular motor functions seen in premature children. For example, the visual fixation is often more instable in the premature child. Also the saccadic as well as the smooth pursuit and vergence systems exhibit delays in development in the premature child. The delayed development has implications for the clinical investigation and must be taken into consideration when examining the visual functions of the premature child.
Visual impairment in children born before 25 gestational weeks ‐ boys are more vulnerable than girls
Authors: JACOBSON L
Published: September 2009

Purpose To describe the frequency of ROP and visual impairment with respect to gender in children born at gestational ages (GA) before 25 weeks.

Methods In a population‐based group of children born at GA <25+0 1990‐2002, who survived to 4 years of age (n=114), maximal ROP stages, treatment and visual outcome were followed up.

Results Almost all (97,4%) children had ROP and 63,2% were treated with retinal ablation. Visual impairment (VA<0.33) was more common in boys (32,6%)than in girls (9,2%). All visually impaired children but one had severe ROP as the primary cause of their visual impairment. Almost all visually impaired children had additional functional deficits.

Conclusion A large proportion of children born before 25 gestational weeks are visually impaired in spite of screening and treatment of ROP. Almost all visually impaired children in this group have additional functional deficits due to cerebral dysfunction.