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Sample records for advanced primary open-angle

  1. Primary open-angle glaucoma.

    PubMed

    Weinreb, Robert N; Khaw, Peng Tee

    2004-05-22

    Primary open-angle glaucoma is a progressive optic neuropathy and, perhaps, the most common form of glaucoma. Because the disease is treatable, and because the visual impairment caused by glaucoma is irreversible, early detection is essential. Early diagnosis depends on examination of the optic disc, retinal nerve fibre layer, and visual field. New imaging and psychophysical tests can improve both detection and monitoring of the progression of the disease. Recently completed long-term clinical trials provide convincing evidence that lowering intraocular pressure prevents progression at both the early and late stages of the disease. The degree of protection is related to the degree to which intraocular pressure is lowered. Improvements in therapy consist of more effective and better-tolerated drugs to lower intraocular pressure, and more effective surgical procedures. New treatments to directly treat and protect the retinal ganglion cells that are damaged in glaucoma are also in development.

  2. Linkage studies in primary open angle glaucoma

    SciTech Connect

    Avramopoulos, D.; Grigoriadu, M.; Kitsos, G.

    1994-09-01

    Glaucoma is a leading cause of blindness worldwide. The majority of glaucoma is associated with an open, normal appearing anterior chamber angle and is termed primary open angle glaucoma (POAG, MIM 137760). It is characterized by elevated intraocular pressure and onset in middle age or later. A subset of POAG with juvenile onset has recently been linked to chromosome 1q in two families with autosomal dominant inheritance. Eleven pedigrees with autosomal dominant POG (non-juvenile-onset) have been identified in Epirus, Greece. In the present study DNA samples have been collected from 50 individuals from one large pedigree, including 12 affected individuals. Preliminary results of linkage analysis with chromosome 1 microsatellites using the computer program package LINKAGE Version 5.1 showed no linkage with the markers previously linked to juvenile-onset POAG. Further linkage analysis is being pursued, and the results will be presented.

  3. Measurement of Systemic Mitochondrial Function in Advanced Primary Open-Angle Glaucoma and Leber Hereditary Optic Neuropathy.

    PubMed

    Van Bergen, Nicole J; Crowston, Jonathan G; Craig, Jamie E; Burdon, Kathryn P; Kearns, Lisa S; Sharma, Shiwani; Hewitt, Alex W; Mackey, David A; Trounce, Ian A

    2015-01-01

    Primary Open Angle Glaucoma (POAG) is a common neurodegenerative disease characterized by the selective and gradual loss of retinal ganglion cells (RGCs). Aging and increased intraocular pressure (IOP) are glaucoma risk factors; nevertheless patients deteriorate at all levels of IOP, implying other causative factors. Recent evidence presents mitochondrial oxidative phosphorylation (OXPHOS) complex-I impairments in POAG. Leber Hereditary Optic Neuropathy (LHON) patients suffer specific and rapid loss of RGCs, predominantly in young adult males, due to complex-I mutations in the mitochondrial genome. This study directly compares the degree of OXPHOS impairment in POAG and LHON patients, testing the hypothesis that the milder clinical disease in POAG is due to a milder complex-I impairment. To assess overall mitochondrial capacity, cells can be forced to produce ATP primarily from mitochondrial OXPHOS by switching the media carbon source to galactose. Under these conditions POAG lymphoblasts grew 1.47 times slower than controls, whilst LHON lymphoblasts demonstrated a greater degree of growth impairment (2.35 times slower). Complex-I enzyme specific activity was reduced by 18% in POAG lymphoblasts and by 29% in LHON lymphoblasts. We also assessed complex-I ATP synthesis, which was 19% decreased in POAG patients and 17% decreased in LHON patients. This study demonstrates both POAG and LHON lymphoblasts have impaired complex-I, and in the majority of aspects the functional defects in POAG were milder than LHON, which could reflect the milder disease development of POAG. This new evidence places POAG in the spectrum of mitochondrial optic neuropathies and raises the possibility for new therapeutic targets aimed at improving mitochondrial function.

  4. Canaloplasty versus Viscocanalostomy in Primary Open Angle Glaucoma

    PubMed Central

    Wagdy, Faried Mohammed

    2017-01-01

    Introduction The purpose of this study was to compare the efficacy and safety of canaloplasty versus viscocanalostomy in management of uncontrolled primary open angle glaucoma (POAG) with medication. Methods Canaloplasty surgery was applied for thirty eyes of thirty patients (45–55 years) with a mean age of 48 years (Group A) and viscocanalostomy surgery was applied also for thirty eyes of thirty patients (43–54 years) with a mean age of 46 years (group B). All patients were with uncontrolled primary open angle glaucoma by maximally tolerated medical therapy. Results Intraocular pressure (IOP) in both surgeries was significantly reduced through follow up period (p < 0.0.001). Complete success was 86.6% in group A and 80% in group B. Visual field deterioration was in 2 cases (6%) in group A and in 4 cases (13%) in group B. Low incidence of postoperative complications was reported as Descemet’s membrane detachment (3% in group A and 8% in group B), ocular hypotony (2% in group A and 4% in group B) and hyphema (3% in group A and 5% in group B). Conclusion Canaloplasty was more effective and safer than viscocanalostomy in management of uncontrolled primary open angle glaucoma (POAG) with medication. PMID:28243422

  5. Current primary open-angle glaucoma treatments and future directions

    PubMed Central

    Beidoe, Gabriel; Mousa, Shaker A

    2012-01-01

    Primary open-angle glaucoma (POAG) is a leading cause of blindness with no known cure. Management of the disease focuses on lowering intraocular pressure (IOP) with current classes of drugs like prostaglandin analogs, beta-blockers, alpha-agonists, and carbonic anhydrase inhibitors. These treatments have not helped all patients. Some patients continue to experience deterioration in the optic nerve even though their IOPs are within the normal range. New views have surfaced about other pathophysiological processes (such as oxidative stress, vascular dysfunction, and retinal cell apoptosis) being involved in POAG progression, and adjunctive treatments with drugs like memantine, bis(7)-tacrine, nimodipine, and mirtogenol are advocated. This review examines the current and proposed treatments for POAG. Some of the proposed drugs (bis(7)-tacrine, nimodipine, vitamin E, and others) have shown good promise, mostly as monotherapy in various clinical trials. It is recommended that both the current and proposed drugs be put through further robust trials in concurrent administration and evaluated. PMID:23118520

  6. Race, ethnicity and prevalence of primary open-angle glaucoma.

    PubMed Central

    Kosoko-Lasaki, Omofolasade; Gong, Gordon; Haynatzki, Gleb; Wilson, M. Roy

    2006-01-01

    BACKGROUND: Recently, some authors pooled data from studies on the Dutch, Australians and Americans of European origin in an attempt to predict the prevalence of primary open-angle glaucoma (POAG) in the United States. PURPOSE: To examine potential ethnic diversity in the prevalence of POAG among populations of the "same race." Methods: Medical literature was searched, and 11 population-based studies on populations of African origin and five on populations of European origin were identified. RESULTS: The prevalence of POAG was significantly higher in white Australians than in the Dutch (p<0.001) and was significantly lower (p<0.001) among black populations in South Africa, Nigeria, Tanzania and the United States than in Ghana, St. Lucia or Barbados. Notably, the prevalence was significantly lower in Afro Caribbeans living in London than in St. Lucia or Barbados (p<0.001). There was, however, inconsistency in the definition of POAG among the different studies. CONCLUSIONS: There is a wide range in the prevalence of POAG among populations of the same "race," which might be attributed to the different methodology and definition of POAG; potential difference in social, behavioral and environmental factors; and/or genetic predisposition. Scrutiny is warranted when pooling data from different ethnic groups of the "same race" in meta-analyses. PMID:17052053

  7. Vascular and Autonomic Dysregulation in Primary Open-Angle Glaucoma

    PubMed Central

    Pasquale, Louis R.

    2015-01-01

    Purpose of the review To discuss whether vascular dysfunction and autonomic dysfunction are related to primary open-angle glaucoma stratified by the intraocular pressure (IOP) level (the high tension glaucoma and normal tension glaucoma subtypes). Recent findings Patients with POAG across the spectrum of IOP exhibit a variety of ocular and non-ocular vascular abnormalities. Interestingly common genetic variation in NOS3 and the CAV1/CAV2 genomic regions, which code for proteins involved in setting vascular tone, are associated with POAG. These markers seem to stratify with POAG subtypes by sex or pattern of initial visual field loss. Overall it is clear that there is also cardiovascular autonomic dysfunction in HTG and NTG but it is unclear if this dysfunction is more common in NTG compared to HTG. Summary Overall POAG is likely a heterogeneous disease but stratifying cases by IOP level associated with initial optic nerve damage may be less useful than using other endophenotype approaches. Embracing the evidence suggesting systemic endothelial and autonomic dysfunction are operative in POAG will help move beyond an IOP-centric view of the disease and facilitate “tearing down the wall” that divides treating physicians and a better understanding of POAG pathogenesis. PMID:26720776

  8. Screening of candidate genes for primary open angle glaucoma

    PubMed Central

    Liu, Ting; Xie, Lin; Ye, Jian; Liu, Yuewuyang

    2012-01-01

    Purpose Primary open-angle glaucoma (POAG) is one of the leading causes of irreversible blindness in the world. To make progress in understanding POAG, it is necessary to identify more POAG-causing genes. Methods Using haplotype analysis, we found that mutational region is located on chromosome 2 in two families. Furthermore, we screened 11 candidate genes on chromosome 2 by protein–protein interaction (PPI) analysis, including mutS homolog 6 (MSH6), mutS homolog 2 (MSH2), v-rel reticuloendotheliosis viral oncogene homolog (REL), endothelial PAS domain protein 1 (EPAS1), vaccinia related kinase 2 (VRK2), F-box protein 11 (FBXO11), EGF containing fibulin-like extracellular matrix protein 1 (EFEMP1), reticulon 4 (RTN4), RAB1A, member RAS oncogene family (RAB1A), ARP2 actin-related protein 2 homolog (ACTR2), and calmodulin 2 (phosphorylase kinase, delta; CALM2). These 11 genes are all predicted to be related to trabecular meshwork changes and progressive loss of retinal ganglion cells in POAG patients. Results According to our study, FBXO11 and VRK2 may interact with tumor protein p53 to regulate mitochondrial membrane permeability, mitochondrial membrane organization, and apoptosis. MSH2 is responsible for repairing DNA mismatches and RTN4 is for neuronal regeneration. Therefore, they are supposed to play a negative role in cellular process in POAG. CALM2 may be involved in retinal ganglion cell death and oxidative damage to cell communication. Conclusions The results demonstrate that the genes above may be associated with pathogenesis of POAG. PMID:22876139

  9. Retinal oximetry in primary open-angle glaucoma.

    PubMed

    Olafsdottir, Olof Birna; Hardarson, Sveinn Hakon; Gottfredsdottir, Maria Soffia; Harris, Alon; Stefánsson, Einar

    2011-08-16

    PURPOSE. To determine whether retinal vessel oxygen saturation is affected in primary open-angle glaucoma (POAG) patients. METHODS. Retinal oxygen saturation in patients with POAG was measured in retinal vessels with a spectrophotometric retinal oximeter in darkness, and visual fields were obtained. Oxygen tension (Po(2)) was calculated from oxygen saturation values. Statistical analysis was performed using Pearson's correlation and Student's t-test. RESULTS. Mean oxygen saturation in venules was higher in persons with poor visual fields (68% ± 4%, mean ± SD) than in those with good visual fields (62% ± 3%; P = 0.0018). The mean arteriovenous difference in oxygen saturation was lower in persons with poor visual fields (30% ± 4%, n = 9) than in those with good visual fields (37% ± 4%; P = 0.0003; n = 12). No correlation was found between saturation in retinal arterioles and visual field mean defect (n = 31; r = -0.16; P = 0.38). Oxygen saturation in retinal venules correlated positively with worsening visual field mean defect (r = 0.43; P = 0.015). Arteriovenous difference in oxygen saturation decreased significantly as the visual field mean defect worsened (r = -0.55; P = 0.0013). Mean Po(2) in venules was 38 ± 3 mm Hg. It was significantly higher in persons with poor visual field fields (40 ± 3 mm Hg) than in those with good visual fields (36 ± 2 mm Hg; P = 0.0016). CONCLUSIONS. Deeper glaucomatous visual field defects are associated with increased oxygen saturation in venules and decreased arteriovenous difference in retinal oxygen saturation. The data suggest that oxygen metabolism is affected in the glaucomatous retina, possibly related to tissue atrophy.

  10. The inheritance of juvenile onset primary open angle glaucoma.

    PubMed

    Gupta, V; Somarajan, B I; Gupta, S; Chaurasia, A K; Kumar, S; Dutta, P; Gupta, V; Sharma, A; Tayo, B O; Nischal, K

    2016-10-25

    Juvenile onset open angle glaucoma (JOAG) affects patients before 40 years of age, who present with high intraocular pressure and deep steep cupping of the optic nerve head. While it was considered to be inherited in an autosomal dominant fashion, recent studies have shown an autosomal recessive pattern as well as sporadic occurrence of the disease in several families. In this review, we analyze the genetic basis of the disease along with common mutations and their association with JOAG. We also analyzed the inheritance patterns in a large group of unrelated JOAG patients (n = 336) from Northern India wherein the prevalence of familial occurrence was assessed and segregation analysis performed, to determine the mode of inheritance.

  11. Analysis of the qualitative dermatoglyphics of the digito-palmar complex in patients with primary open angle glaucoma.

    PubMed

    Novak-Laus, Katia; Milicić, Jasna; Tedeschi-Reiner, Eugenia; Iveković, Renata; Korsić, Jadranka; Zrinsćak, Ognjen; Mandić, Zdravko

    2006-03-01

    The primary open-angle glaucomas are a group of diseases that have in common characteristic morphological changes at the optic nerve head and retinal nerve fiber layer, progressive retinal ganglion cells death and characteristic visual field loss. The risk for primary open angle glaucoma rises continuously with the level of the intraocular pressure. The disease advances slowly and there are no symptoms. Primary open angle glaucoma is caused by abnormal aqueous humour outflow in the trabecular meshwork in the open angle. Etiopathogenesis of primary open angle glaucoma is unclear. The increased risk of glaucoma in relatives has long been recognized. Frequency for manifestation of the disease is 10-30% in family members. The discovery of the specific gene loci responsible for the manifestation of glaucoma has helped us to understand its mechanism of origin and definitely confirmed the hereditary nature of this disease. Digito-palmar dermatoglyphs were already used to determine hereditary base of many diseases and it was the reason for investigation of their qualitative patterns in patients with glaucoma (22 males and 23 females), their immediate relatives (19 males and 23 females) in comparison to a group of phenotypically healthy population (52 males and 56 females). The results pointed a connection with the dermatoglyphic traits of the digito-palmar complex between patients with glaucoma and their immediate relatives. There is a possible discrimination of patients and their immediate relatives from phenotypically healthy population, too.

  12. The distinction between juvenile and adult-onset primary open-angle glaucoma

    SciTech Connect

    Wiggs, J.L.; Haines, J.L.; Damji, K.F.

    1996-01-01

    Because of the significant differences between the juvenile and adult forms of open-angle glaucoma, especially with regard to inheritance, prevalence, severity, and age of onset, we read with interest the recent publication by Morissette et al., describing a pedigree with a phenotype that overlaps the distinctive features of juvenile-onset open-angle glaucoma (JOAG) and adult-onset primary open-angle glaucoma (usually abbreviated as POAG or COAG). These authors conclude that a gene mapped to human chromosome 1q21-q31 (GLC1A) can be responsible for both juvenile and adult forms of open-angle glaucoma. The implications of such a result could be extremely important, in light of the high prevalence of the adult form of the disease. However, while the data presented in this report suggest that variable expressivity of the GLC1A gene may lead to a broader range of onset for this form of juvenile glaucoma, these data do not identify the GLC1A gene as an important cause of POAG. To prevent misleading interpretations of this and similar studies, we wish to clarify the distinction between the juvenile and adult forms of open-angle glaucoma. 8 refs.

  13. Changing Concepts of Primary Open-Angle Glaucoma and Early Detection

    PubMed Central

    Battista, Renaldo N.; Huston, Patricia; Davis, M. William L.

    1986-01-01

    The understanding of primary open-angle glaucoma has changed over the past 20 years and recommendations on early detection are being revised. In this paper the use of Shiotz tonometry is critically examined, and the problems encountered in instituting alternative screening techniques are reviewed. ImagesFigure 3c PMID:21267099

  14. Novel Pharmacologic Candidates for Treatment of Primary Open-Angle Glaucoma

    PubMed Central

    Lu, Louise J.; Tsai, James C.; Liu, Ji

    2017-01-01

    Primary open-angle glaucoma (OAG) affects approximately 45 million people worldwide and more than 2.5 million people aged 40 years or older in the United States. Pharmacologic treatment for glaucoma is directed towards lowering intraocular pressure (IOP) to slow disease progression and delay visual field loss. Current medical treatment options for the lowering of IOP include the following classes of topical medications: beta-adrenergic antagonists, alpha-adrenergic agonists, cholinergic agonists, carbonic anhydrase inhibitors, and prostaglandin analogs. Issues with existing drugs include failure to achieve target IOP with monotherapy, drug-related side effects, and low patient compliance with multiple daily administration of eye drops. In recent years, the scientific and medical community has seen encouraging development of novel classes of drugs for primary OAG, the majority of which lower IOP by targeting the trabecular meshwork outflow pathway to increase aqueous humor outflow. Among the most promising new pharmacologic candidates are rho kinase inhibitors including ripasudil (K-115), netarsudil (AR-13324), and AMA0076; adenosine receptor agonists including trabodenoson (INO-8875); and modified prostaglandin analogs including latanoprostene bunod (LBN, BOL-303259-X) and ONO-9054. This study aims to systematically review and summarize the most recent developments in clinical trials for new pharmacologic options for the treatment of primary open-angle glaucoma. PMID:28356898

  15. [The effect of crystalline lens extraction on intraocular pressure in patients with primary open-angle glaucoma].

    PubMed

    Macarie, S; Macarie, Daniela

    2013-01-01

    This issue presents the results of a study on patients with cataract and primary open angle glaucoma who suffered lens extraction for cataract. We analise the effects of the lens extraction on the level of intraocular pressure at this patients.

  16. Molecular biomarkers in primary open-angle glaucoma: from noninvasive to invasive.

    PubMed

    Agnifili, Luca; Pieragostino, Damiana; Mastropasqua, Alessandra; Fasanella, Vincenzo; Brescia, Lorenza; Tosi, Gian Marco; Sacchetta, Paolo; Mastropasqua, Leonardo

    2015-01-01

    Glaucoma, the first cause of irreversible blindness worldwide, is a neurodegenerative disease characterized by the progressive loss of retinal ganglion cells. There are different subtypes of glaucoma, all expression of a common optic neuropathy; primary open-angle glaucoma (POAG) is the most diffuse subtype in western countries. To date, unfortunately, several questions still remain unsolved in the glaucoma management, such as the availability of powerful methods for screening high-risk populations, early diagnosis, timely detection of damage progression, and prediction of response to therapy. Over the last years, biomarkers have gained immense scientific and clinical interest to solve these issues, with countless molecules that have been candidate as potential biomarkers. In the present review, we summarize the current knowledge about the most robust molecular biomarkers proposed in POAG, distinguishing noninvasive from minimally invasive, and invasive biomarkers, according to the procedure adopted to collect fluid samples.

  17. A common variant near TGFBR3 is associated with primary open angle glaucoma.

    PubMed

    Li, Zheng; Allingham, R Rand; Nakano, Masakazu; Jia, Liyun; Chen, Yuhong; Ikeda, Yoko; Mani, Baskaran; Chen, Li-Jia; Kee, Changwon; Garway-Heath, David F; Sripriya, Sarangapani; Fuse, Nobuo; Abu-Amero, Khaled K; Huang, Chukai; Namburi, Prasanthi; Burdon, Kathryn; Perera, Shamira A; Gharahkhani, Puya; Lin, Ying; Ueno, Morio; Ozaki, Mineo; Mizoguchi, Takanori; Krishnadas, Subbiah Ramasamy; Osman, Essam A; Lee, Mei Chin; Chan, Anita S Y; Tajudin, Liza-Sharmini A; Do, Tan; Goncalves, Aurelien; Reynier, Pascal; Zhang, Hong; Bourne, Rupert; Goh, David; Broadway, David; Husain, Rahat; Negi, Anil K; Su, Daniel H; Ho, Ching-Lin; Blanco, Augusto Azuara; Leung, Christopher K S; Wong, Tina T; Yakub, Azhany; Liu, Yutao; Nongpiur, Monisha E; Han, Jong Chul; Hon, Do Nhu; Shantha, Balekudaru; Zhao, Bowen; Sang, Jinghong; Zhang, NiHong; Sato, Ryuichi; Yoshii, Kengo; Panda-Jonas, Songhomita; Ashley Koch, Allison E; Herndon, Leon W; Moroi, Sayoko E; Challa, Pratap; Foo, Jia Nee; Bei, Jin-Xin; Zeng, Yi-Xin; Simmons, Cameron P; Bich Chau, Tran Nguyen; Sharmila, Philomenadin Ferdinamarie; Chew, Merwyn; Lim, Blanche; Tam, Pansy O S; Chua, Elaine; Ng, Xiao Yu; Yong, Victor H K; Chong, Yaan Fun; Meah, Wee Yang; Vijayan, Saravanan; Seongsoo, Sohn; Xu, Wang; Teo, Yik Ying; Cooke Bailey, Jessica N; Kang, Jae H; Haines, Jonathan L; Cheng, Ching Yu; Saw, Seang-Mei; Tai, E-Shyong; Richards, Julia E; Ritch, Robert; Gaasterland, Douglas E; Pasquale, Louis R; Liu, Jianjun; Jonas, Jost B; Milea, Dan; George, Ronnie; Al-Obeidan, Saleh A; Mori, Kazuhiko; Macgregor, Stuart; Hewitt, Alex W; Girkin, Christopher A; Zhang, Mingzhi; Sundaresan, Periasamy; Vijaya, Lingam; Mackey, David A; Wong, Tien Yin; Craig, Jamie E; Sun, Xinghuai; Kinoshita, Shigeru; Wiggs, Janey L; Khor, Chiea-Chuen; Yang, Zhenglin; Pang, Chi Pui; Wang, Ningli; Hauser, Michael A; Tashiro, Kei; Aung, Tin; Vithana, Eranga N

    2015-07-01

    Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease with a significant genetic contribution. We performed Exome Array (Illumina) analysis on 3504 POAG cases and 9746 controls with replication of the most significant findings in 9173 POAG cases and 26 780 controls across 18 collections of Asian, African and European descent. Apart from confirming strong evidence of association at CDKN2B-AS1 (rs2157719 [G], odds ratio [OR] = 0.71, P = 2.81 × 10(-33)), we observed one SNP showing significant association to POAG (CDC7-TGFBR3 rs1192415, ORG-allele = 1.13, Pmeta = 1.60 × 10(-8)). This particular SNP has previously been shown to be strongly associated with optic disc area and vertical cup-to-disc ratio, which are regarded as glaucoma-related quantitative traits. Our study now extends this by directly implicating it in POAG disease pathogenesis.

  18. Mapping a gene for adult-onset primary open-angle glaucoma to chromosome 3q

    SciTech Connect

    Wirtz, M.K.; Samples, J.R.; Kramer, P.L.

    1997-02-01

    Glaucoma is the third-leading cause of blindness in the world, affecting >13.5 million people. Adult-on-set primary open-angle glaucoma (POAG) is the most common form of glaucoma in the United States. We present a family in which adult-onset POAG is inherited as an autosomal dominant trait. Twelve affected family members were identified from 44 at-risk individuals. The disease-causing gene was mapped to chromosome 3q21-24, with analysis of recombinant haplotypes suggesting a total inclusion region of 11.1 cM between markers D3S3637 and D3S1744. This is the first report of mapping of an adult-onset POAG gene to chromosome 3q, gene symbol GLC1C. 57 refs., 3 figs., 3 tabs.

  19. Mapping a gene for adult-onset primary open-angle glaucoma to chromosome 3q.

    PubMed Central

    Wirtz, M K; Samples, J R; Kramer, P L; Rust, K; Topinka, J R; Yount, J; Koler, R D; Acott, T S

    1997-01-01

    Glaucoma is the third-leading cause of blindness in the world, affecting >13.5 million people. Adult-onset primary open-angle glaucoma (POAG) is the most common form of glaucoma in the United States. We present a family in which adult-onset POAG is inherited as an autosomal dominant trait. Twelve affected family members were identified from 44 at-risk individuals. The disease-causing gene was mapped to chromosome 3q21-24, with analysis of recombinant haplotypes suggesting a total inclusion region of 11.1 cM between markers D3S3637 and D3S1744. This is the first report of mapping of an adult-onset POAG gene to chromosome 3q, gene symbol GLC1C. PMID:9012402

  20. A cohort study of duplex Doppler examinations of the carotid artery in primary open angle glaucoma

    PubMed Central

    Marmion, Vincent J; Aldoori, Munther I; Woodcock, John P

    2014-01-01

    Objectives To explore the possibility of pathological change in the common carotid artery at the bifurcation and in the internal carotid artery beyond the bifurcation which could contribute to a reduced diastolic pressure as observed in primary open angle glaucoma. Design Duplex ultrasonic examinations of carotid bifurcations were conducted on 80 patients. Carotid artery defects were allocated into three types: no demonstrable flow defects, internal carotid artery abnormalities and disease in the carotid bulb. Setting Bristol Royal Infirmary Vascular Laboratory. Participants Eighty patients (mean age 69.6 years) providing a total of 160 sides to the analysis. Main outcome measures An estimated central retinal artery pressure, intraocular pressure and field loss were recorded for each side measured. Results Doppler investigations revealed significant levels of pathological change in the internal carotid distinct from changes at the carotid bulb. The disease revealed in the internal carotid artery was significantly associated with intraocular pressure (p = 0.032), with an effect small to medium in magnitude. The Q2 measure, derived from mean arterial pressure and intraocular pressure, was also substantively associated with disease in the internal carotid artery. Both intraocular pressure and the Q2 measure effectively discriminated between groups, with field loss providing rather less discriminating capability. There was a strong trend towards a higher intraocular pressures and a greater visual field loss with internal carotid artery disease. Conclusions Pathological changes in the extra cranial carotid artery in primary open angle glaucoma exceed those in the arteries classified as normal. The presence of disease specifically in the internal carotid artery emphasised the need for a mechanism for the evaluation of the internal carotid apart from the carotid bulb. A basis for clarifying the presence of an ischaemic zone is proposed. PMID:25289141

  1. The Association Between Primary Open Angle Glaucoma and Clustered Components of Metabolic Syndrome

    PubMed Central

    Rasoulinejad, Seyed Ahmad; Kasiri, Ali; Montazeri, Mahdi; Rashidi, Negin; Montazeri, Maryam; Montazeri, Mohammad; Hedayati, Hesam

    2015-01-01

    Purpose : There is conflicting evidence whether components of metabolic syndrome (MetS) increase or decrease the risk of primary open-angle glaucoma (POAG). The aim of the present study was to determine the association between metabolic syndrome and primary open-angle glaucoma. Methods : A total of 200 participants comprising 100 controls and 100 patients with POAG documented by clinical tests and examined by an experienced ophthalmologist using standard ophthalmologic equipment were included in the study. MetS was defined and based on ATP III criteria and POAG was defined by the criteria of the International Society of Geographic and Epidemiological Ophthalmology (ISGEO). The data were entered into the SPSS software and analyzed. Results : The prevalence of MetS in the glaucoma group was 53% in comparison to 38% in the control group (p=0.037). MetS was associated with an increased odds ratio for an IOP higher than 21 mmHg (OR: 1.72; 95% CI 1.03-2.79; p=0.034). The mean IOP was 24.91±4.29 mmHg in the patients without MetS, and 27.23±4.81 mmHg in those with MetS (p=0.027). The mean values of CCT were 603.64±63.16 µm in MetS patients and 579.27±72.87 µm in controls (p=0.018). Conclusion : Data showed an increased prevalence of components of metabolic syndrome in patients with glaucoma. The mechanisms underlying these associations need to be established in future studies. Our results support the recommendation that patients with metabolic syndrome undergo regular ophthalmological exams to monitor for the onset or progression of glaucoma. PMID:26535072

  2. Single nucleotide polymorphisms of metabolic syndrome-related genes in primary open angle glaucoma

    PubMed Central

    Zhou, Gang; Liu, Bin

    2010-01-01

    AIM To analyze single nucleotide polymorphisms (SNP) of primary open angle glaucoma- and metabolic syndrome-related genes in primary open angle glaucoma (POAG), in order to elucidate the roles of metabolic syndrome as a risk factor in POAG progress. METHODS SNP genotypes and alleles of interleukin-6 (IL-6), IL-6 receptor (IL-6R), dopamine D2 receptor (DRD2), beta-fibrinogen (FGB), peroxisome proliferator-activated receptor-γ2 (PPARG), transforming growth factor-β1 (TGF-β1), E-selectin (E-Sel), apolipoprotein A-5 (APOA5), C-reactive protein (CRP), ectonueleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), hepatic lipase (LIPC), adiponectin (ADIPOQ), paraoxonase 1 (PON1) and serine protease inhibitor E (SERPINE1) genes in POAG (n=37) and normal control (n=100) groups were measured with ABI Prism 7900HT Fluorescence Quantitative PCR and TaqMan SNP Genotyping fluorescence probe kit. RESULTS Genotypes and allele frequencies of IL-6R, IL-6, FGB, CRP, ENPP1, LIPC, ADIPOQ, PON1, and SERPINE1 in total POAG group were significantly different compared to the control group. CONCLUSION Metabolic syndrome as a risk factor for POAG may be associated with genotypes and allele frequencies of the related genes. The corresponding gene expression and function can affect POAG progress, including roles of SERPINE1 in extracellular matrix, ENPP1 in insulin inhibition, IL-6 in endogenous neuroprotection, IL-6, IL-6R and E-Sel in autoimmune response, LIPC and FGB in blood hyperviscosity syndrome, ADIPOQ in NOS/NO production, PON1 in vascular endothelial protection. PMID:22553514

  3. Applying the recent clinical trials on primary open angle glaucoma: the developing world perspective.

    PubMed

    Thomas, Ravi; Kumar, Rajesh S; Chandrasekhar, G; Parikh, Rajul

    2005-08-01

    Recent clinical trials have provided scientific guidelines for the treatment of ocular hypertension and primary open angle glaucoma. The developing world need to apply these trials in a sensible and cost effective manner. The number needed to treat (NNT) attempts to tailor treatment to the individual patient. The NNT for the average ocular hypertensive is 20. Those with intraocular pressure > or =26 mm Hg have an NNT of 6. Restricting treatment to those with lower central corneal thickness and or high cup disc ratios can further lower NNT and make treatment more cost effective. The NNT for the average patient with early POAG is 5. Targeting those at higher risk for progression, (bilateral POAG, higher IOP and or pseudo-exfoliation) can further reduce NNT. As far as the modality of treatment is concerned, provided quality can be ensured, collaborative initial glaucoma treatment study (CIGTS) could be interpreted to justify primary surgery in the developing world context. Population attributable risk percentage (PAR), a measure that reflects the public health importance of a disease was used to extrapolate results to the overall population. Ocular hypertension has an "effective" PAR of 8.5%, a value not considered high enough to warrant public health intervention. POAG had an "effective" PAR of 16%, perhaps high enough to be considered a public health problem and justify inclusion as a target disease in the Vision 2020 program. However the logistics and opportunity costs of diagnosis and treatment would probably prevent inclusion of POAG in public health budgets of most developing countries.

  4. The Primary Open-Angle African-American Glaucoma Genetics (POAAGG) Study: Baseline Demographics

    PubMed Central

    Charlson, Emily S.; Sankar, Prithvi S.; Miller-Ellis, Eydie; Regina, Meredith; Fertig, Raymond; Salinas, Julia; Pistilli, Maxwell; Salowe, Rebecca J.; Rhodes, Allison L.; Merritt, William T.; Chua, Michael; Trachtman, Benjamin T.; Gudiseva, Harini V.; Collins, David W.; Chavali, Venkata Ramana Murthy; Nichols, Charles; Henderer, Jeffrey; Ying, Gui-shuang; Varma, Rohit; Jorgenson, Eric

    2014-01-01

    Objective To describe the baseline characteristics of the Primary Open-Angle African-American Glaucoma Genetics (POAAGG) study cohort, the largest African-American primary open-angle glaucoma (POAG) population recruited at a single institution (University of Pennsylvania, Department of Ophthalmology, Scheie Eye Institute) to date. Design Population-based, cross-sectional, case-control study. Participants 2,520 African-American subjects 35 years and older, recruited from the greater Philadelphia, Pennsylvania area. Methods Each subject underwent a detailed interview and eye examination. The interview assessed demographic, behavioral, medical, and ocular risk factors. Current zip codes surrounding the University of Pennsylvania were recorded and United States census data were queried to infer socioeconomic status. The eye exam included measurement of visual acuity and intraocular pressure, a detailed anterior and posterior segment examination including gonioscopy, dilated fundus and optic disc examination, visual fields, stereo disc photography, optical coherence tomography imaging, and measurement of central corneal thickness. Main Outcome Measures The baseline characteristics of gender, age, and glaucoma diagnosis were collected. Body mass index (BMI), hypertension, diabetes, and alcohol and tobacco use, as well as ocular conditions including blindness, cataract, non-proliferative diabetic retinopathy, age-related macular degeneration, and use of ocular medication and surgery, were examined. Median population density, income, education level, and other socioeconomic measures were determined for the study cohort. Results Of the 2,520 African-Americans recruited to the POAAGG study to date, 2,067 (82.0%) including 807 controls and 1,260 POAG cases met all inclusion criteria and completed the detailed clinical ocular exam. Cases were more likely to have a lower BMI (p<0.01) and report a history of blindness (visual acuity of 20/200 or worse, p<0.001), while controls

  5. [Magnetotherapy designed to affect cervical sympathetic ganglia for the treatment of patients with primary open-angle glaucoma].

    PubMed

    Veselova, E V; Kamenskikh, T G; Raĭgorodkiĭ, Iu M; Kolbenev, I O; Myshkina, E S

    2010-01-01

    The traveling magnetic field was used to treat primary open-angle glaucoma. The field was applied to the projection of cervical sympathetic ganglia of the patients. Hemodynamic parameters of posterior short ciliary arteries and central retinal artery were analysed along with visual evoked potentials, visual field limits, and visual acuity. It was shown that magnetotherapy with the use of an AMO-ATOS apparatus produces better clinical results in patients with stage I and II primary open-angle glaucoma compared with medicamentous therapy (intake of trental tablets).

  6. Anti-Neurotrophic Effects from Autoantibodies in Adult Diabetes Having Primary Open Angle Glaucoma or Dementia

    PubMed Central

    Zimering, Mark B.; Moritz, Thomas E.; Donnelly, Robert J.

    2013-01-01

    Aim: To test for anti-endothelial and anti-neurotrophic effects from autoantibodies in subsets of diabetes having open-angle glaucoma, dementia, or control subjects. Methods: Protein-A eluates from plasma of 20 diabetic subjects having glaucoma or suspects and 34 age-matched controls were tested for effects on neurite outgrowth in rat pheochromocytoma PC12 cells or endothelial cell survival. The mechanism of the diabetic glaucoma autoantibodies’ neurite-inhibitory effect was investigated in co-incubations with the selective Rho kinase inhibitor Y27632 or the sulfated proteoglycan synthesis inhibitor sodium chlorate. Stored protein-A eluates from certain diabetic glaucoma or dementia subjects which contained long-lasting, highly stable cell inhibitory substances were characterized using mass spectrometry and amino acid sequencing. Results: Diabetic primary open angle glaucoma (POAG) or suspects (n = 20) or diabetic dementia (n = 3) autoantibodies caused significantly greater mean inhibition of neurite outgrowth in PC12 cells (p < 0.0001) compared to autoantibodies in control diabetic (n = 24) or non-diabetic (n = 10) subjects without glaucoma (p < 0.01). Neurite inhibition by the diabetic glaucoma autoantibodies was completely abolished by 10 μM concentrations of Y27632 (n = 4). It was substantially reduced by 30 mM concentrations of sodium chlorate (n = 4). Peak, long-lasting activity survived storage ×5 years at 0–4°C and was associated with a restricted subtype of Ig kappa light chain. Diabetic glaucoma or dementia autoantibodies (n = 5) caused contraction and process retraction in quiescent cerebral cortical astrocytes effects which were blocked by 5 μM concentrations of Y27632. Conclusion: These data suggest that autoantibodies in subsets of adult diabetes having POAG (glaucoma suspects) and/or dementia inhibit neurite outgrowth and promote a reactive astrocyte morphology by a mechanism which may involve

  7. A common variant near TGFBR3 is associated with primary open angle glaucoma

    PubMed Central

    Li, Zheng; Allingham, R. Rand; Nakano, Masakazu; Jia, Liyun; Chen, Yuhong; Ikeda, Yoko; Mani, Baskaran; Chen, Li-Jia; Kee, Changwon; Garway-Heath, David F.; Sripriya, Sarangapani; Fuse, Nobuo; Abu-Amero, Khaled K.; Huang, Chukai; Namburi, Prasanthi; Burdon, Kathryn; Perera, Shamira A.; Gharahkhani, Puya; Lin, Ying; Ueno, Morio; Ozaki, Mineo; Mizoguchi, Takanori; Krishnadas, Subbiah Ramasamy; Osman, Essam A.; Lee, Mei Chin; Chan, Anita S.Y.; Tajudin, Liza-Sharmini A.; Do, Tan; Goncalves, Aurelien; Reynier, Pascal; Zhang, Hong; Bourne, Rupert; Goh, David; Broadway, David; Husain, Rahat; Negi, Anil K.; Su, Daniel H; Ho, Ching-Lin; Blanco, Augusto Azuara; Leung, Christopher K.S.; Wong, Tina T.; Yakub, Azhany; Liu, Yutao; Nongpiur, Monisha E.; Han, Jong Chul; Hon, Do Nhu; Shantha, Balekudaru; Zhao, Bowen; Sang, Jinghong; Zhang, NiHong; Sato, Ryuichi; Yoshii, Kengo; Panda-Jonas, Songhomita; Ashley Koch, Allison E.; Herndon, Leon W.; Moroi, Sayoko E.; Challa, Pratap; Foo, Jia Nee; Bei, Jin-Xin; Zeng, Yi-Xin; Simmons, Cameron P.; Bich Chau, Tran Nguyen; Sharmila, Philomenadin Ferdinamarie; Chew, Merwyn; Lim, Blanche; Tam, Pansy O.S.; Chua, Elaine; Ng, Xiao Yu; Yong, Victor H.K.; Chong, Yaan Fun; Meah, Wee Yang; Vijayan, Saravanan; Seongsoo, Sohn; Xu, Wang; Teo, Yik Ying; Cooke Bailey, Jessica N.; Kang, Jae H.; Haines, Jonathan L.; Cheng, Ching Yu; Saw, Seang-Mei; Tai, E-Shyong; Richards, Julia E.; Ritch, Robert; Gaasterland, Douglas E.; Pasquale, Louis R.; Liu, Jianjun; Jonas, Jost B.; Milea, Dan; George, Ronnie; Al-Obeidan, Saleh A.; Mori, Kazuhiko; Macgregor, Stuart; Hewitt, Alex W.; Girkin, Christopher A.; Zhang, Mingzhi; Sundaresan, Periasamy; Vijaya, Lingam; Mackey, David A.; Wong, Tien Yin; Craig, Jamie E.; Sun, Xinghuai; Kinoshita, Shigeru; Wiggs, Janey L.; Khor, Chiea-Chuen; Yang, Zhenglin; Pang, Chi Pui; Wang, Ningli; Hauser, Michael A.; Tashiro, Kei; Aung, Tin; Vithana, Eranga N.

    2015-01-01

    Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease with a significant genetic contribution. We performed Exome Array (Illumina) analysis on 3504 POAG cases and 9746 controls with replication of the most significant findings in 9173 POAG cases and 26 780 controls across 18 collections of Asian, African and European descent. Apart from confirming strong evidence of association at CDKN2B-AS1 (rs2157719 [G], odds ratio [OR] = 0.71, P = 2.81 × 10−33), we observed one SNP showing significant association to POAG (CDC7–TGFBR3 rs1192415, ORG-allele = 1.13, Pmeta = 1.60 × 10−8). This particular SNP has previously been shown to be strongly associated with optic disc area and vertical cup-to-disc ratio, which are regarded as glaucoma-related quantitative traits. Our study now extends this by directly implicating it in POAG disease pathogenesis. PMID:25861811

  8. Cytokine biomarkers in tear film for primary open-angle glaucoma

    PubMed Central

    Gupta, Divakar; Wen, Joanne C; Huebner, Janet L; Stinnett, Sandra; Kraus, Virginia B; Tseng, Henry C; Walsh, Molly

    2017-01-01

    Purpose To determine the utility of tear film cytokines as biomarkers for early primary open-angle glaucoma (POAG). Methods Patients without POAG and eye drop-naïve patients with newly diagnosed POAG were recruited from an academic hospital-based glaucoma practice. Tear films of recruited patients were obtained and analyzed using a multiplex, high-sensitivity electrochemiluminescent enzyme-linked immunosorbent assay for proinflammatory cytokines (IFNγ, IL-10, IL-12p70, IL-13, IL-1β, IL-2, IL-4, IL-6, IL-8, and TNFα). Results Mean concentrations of tear film cytokines were lower in the glaucoma group for 8 of 10 cytokines tested. IL-12p70 (3.94±2.19 pg/mL in control vs 2.31±1.156 pg/mL in POAG; P=0.035) was significantly lower in the tear film of patients with newly diagnosed POAG. Conclusion Proinflammatory cytokines were lower in eye drop-naïve newly diagnosed glaucoma patients. Tear film cytokine profiles may be used as biomarkers of early POAG. PMID:28260854

  9. Evaluation of brimonidine-timolol fixed combination in patients of primary open-angle glaucoma.

    PubMed

    Joshi, Sachin R; Akat, Pramod B; Ramanand, Jaiprakash B; Ramanand, Sunita J; Karande, Vitthal B; Jain, Suyog S

    2013-12-01

    The aim of present study was to compare the efficacy and safety of fixed combination of brimonidine and timolol with individual components used as monotherapy in patients of primary open angle glaucoma. Patients were randomly assigned to receive brimonidine or timolol or brimonidine-timolol fixed combination, with 30 patients in each group. The mean reduction in intraocular pressure in brimonidine, timolol, and brimonidine-timolol group were 4.29 ± 1.97 mm Hg, 4.34 ± 1.21 mm Hg, and 5.54 ± 1.87 mm Hg respectively at 2 weeks and 4.86 ± 1.16 mm Hg, 5.42 ± 1.50 mm Hg, and 7.36 ± 2.58 mm Hg respectively at 6 weeks. When values of mean reduction in intraocular pressure were compared between brimonidine-timolol fixed combination with brimonidine and timolol, it was found to be statistically significant ( P < 0.05) at 2 weeks and highly significant (0.001) at 6 weeks. The overall frequency of adverse effects was similar in all three groups.

  10. Short-term effects of relaxation music on patients suffering from primary open-angle glaucoma

    PubMed Central

    Bertelmann, Thomas; Strempel, Ilse

    2015-01-01

    Purpose To evaluate whether additive relaxation music (RM) has an adjuvant short-term effect on physiological and psychological parameters in patients with primary open-angle glaucoma. Methods Prospective, randomized clinical trial. Patients in the therapy group (TG) received a 30-minute RM via headphones, whereas members of the control group (CG) did not. Best corrected visual acuity, intraocular pressure, visual field testing, short- and long-term mental states, and blood levels of different stress hormones were analyzed and compared. Results A total of 25 (61%)/16 (39%) patients were assigned to the TG/CG. Best corrected visual acuity, daily intraocular pressure, and short-term mental state (KAB) development were significantly better in the TG in comparison to controls. Visual field testing, long-term mental well-being (profile of mood states), and adrenalin, cortisol, and endothelin-I blood levels did not differ significantly between both groups. Conclusion Additive RM applied on a daily basis can positively impact various physiological and psychological parameters in the short term. PMID:26543350

  11. Electrophysiological and psychophysical flicker sensitivity in patients with primary open-angle glaucoma and ocular hypertension.

    PubMed

    Holopigian, K; Seiple, W; Mayron, C; Koty, R; Lorenzo, M

    1990-09-01

    Temporal sensitivity was assessed in patients with primary open-angle glaucoma (POAG) and ocular hypertension (OHT). Three measures of flicker sensitivity were obtained: psychophysical modulation thresholds, visual-evoked potentials (VEPs), and focal electroretinograms (FERGs). We found elevated psychophysical thresholds at higher temporal frequencies (30-50 Hz) in patients with POAG, relative to thresholds for age-matched controls. The OHT patients had elevated psychophysical thresholds only at 50 Hz. On the other hand, VEP amplitudes in POAG patients were reduced at all temporal frequencies, with the magnitude of the loss increasing with temporal frequency. The OHT patients, however, showed no reductions in VEP amplitude at any temporal frequency. Finally, POAG patients' FERG amplitudes were reduced at 30-50 Hz; whereas FERG amplitudes in the OHT patients were normal at all temporal frequencies. These results indicate that OHT patients can exhibit psychophysical threshold losses at high temporal frequencies which are not observed in the suprathreshold electrophysiological amplitude measures. On the other hand, patients with POAG show both psychophysical and VEP losses across a range of temporal frequencies. In addition, the decreases in FERG amplitudes in POAG patients suggest changes in the functioning of the outer retina in this disease.

  12. Red blood cell plasmalogens and docosahexaenoic acid are independently reduced in primary open-angle glaucoma.

    PubMed

    Acar, Niyazi; Berdeaux, Olivier; Juaneda, Pierre; Grégoire, Stéphane; Cabaret, Stéphanie; Joffre, Corinne; Creuzot-Garcher, Catherine P; Bretillon, Lionel; Bron, Alain M

    2009-12-01

    Among several theories involved in the pathogenesis of primary open-angle glaucoma (POAG), the vascular theory considers the disease to be a consequence of reduced ocular blood flow associated with red blood cell abnormalities. Red blood cell membrane structure and function are influenced by their phospholipid composition. We investigated whether specific lipid entities that may affect the membrane physiology, namely, polyunsaturated fatty acids (PUFAs) and plasmalogens, are modified in POAG and whether these potential variations are related to the stage of glaucoma. Blood samples were collected from 31 POAG patients and 10 healthy individuals. The stage of glaucoma was determined according to the Hodapp and Parrish classification. Lipids were extracted from red blood cell membranes and individual phospholipid species were quantified by liquid chromatography combined with mass spectrometry using triple quadrupole technology. POAG patients had reduced erythrocyte levels of phosphatidyl-choline (PC) carrying docosahexaenoic acid (DHA). POAG patients also displayed lower levels of choline plasmalogens (PlsC) carrying PUFAs other than DHA. These differences were greater as the severity of the disease increased. Linear regressions predicted that red blood cell PlsC levels would decrease years before clinical symptoms, whereas the levels of PC carrying DHA were linearly correlated to visual field loss. Our data demonstrate the selective loss of some individual phospholipid species in red blood cell membranes, which may partly explain their loss of flexibility in POAG.

  13. Assessment of polygenic effects links primary open-angle glaucoma and age-related macular degeneration.

    PubMed

    Cuellar-Partida, Gabriel; Craig, Jamie E; Burdon, Kathryn P; Wang, Jie Jin; Vote, Brendan J; Souzeau, Emmanuelle; McAllister, Ian L; Isaacs, Timothy; Lake, Stewart; Mackey, David A; Constable, Ian J; Mitchell, Paul; Hewitt, Alex W; MacGregor, Stuart

    2016-05-31

    Primary open-angle glaucoma (POAG) and age-related macular degeneration (AMD) are leading causes of irreversible blindness. Several loci have been mapped using genome-wide association studies. Until very recently, there was no recognized overlap in the genetic contribution to AMD and POAG. At genome-wide significance level, only ABCA1 harbors associations to both diseases. Here, we investigated the genetic architecture of POAG and AMD using genome-wide array data. We estimated the heritability for POAG (h(2)g = 0.42 ± 0.09) and AMD (h(2)g = 0.71 ± 0.08). Removing known loci for POAG and AMD decreased the h(2)g estimates to 0.36 and 0.24, respectively. There was evidence for a positive genetic correlation between POAG and AMD (rg = 0.47 ± 0.25) which remained after removing known loci (rg = 0.64 ± 0.31). We also found that the genetic correlation between sexes for POAG was likely to be less than 1 (rg = 0.33 ± 0.24), suggesting that differences of prevalence among genders may be partly due to heritable factors.

  14. Assessment of polygenic effects links primary open-angle glaucoma and age-related macular degeneration

    PubMed Central

    Cuellar-Partida, Gabriel; Craig, Jamie E.; Burdon, Kathryn P.; Wang, Jie Jin; Vote, Brendan J.; Souzeau, Emmanuelle; McAllister, Ian L.; Isaacs, Timothy; Lake, Stewart; Mackey, David A.; Constable, Ian J.; Mitchell, Paul; Hewitt, Alex W.; MacGregor, Stuart

    2016-01-01

    Primary open-angle glaucoma (POAG) and age-related macular degeneration (AMD) are leading causes of irreversible blindness. Several loci have been mapped using genome-wide association studies. Until very recently, there was no recognized overlap in the genetic contribution to AMD and POAG. At genome-wide significance level, only ABCA1 harbors associations to both diseases. Here, we investigated the genetic architecture of POAG and AMD using genome-wide array data. We estimated the heritability for POAG (h2g = 0.42 ± 0.09) and AMD (h2g = 0.71 ± 0.08). Removing known loci for POAG and AMD decreased the h2g estimates to 0.36 and 0.24, respectively. There was evidence for a positive genetic correlation between POAG and AMD (rg = 0.47 ± 0.25) which remained after removing known loci (rg = 0.64 ± 0.31). We also found that the genetic correlation between sexes for POAG was likely to be less than 1 (rg = 0.33 ± 0.24), suggesting that differences of prevalence among genders may be partly due to heritable factors. PMID:27241461

  15. Selective laser trabeculoplasty (SLT): 1-year results in early and advanced open angle glaucoma.

    PubMed

    Schlote, Torsten; Kynigopoulos, Myron

    2016-02-01

    The purpose of this study was to examine the efficacy of selective laser trabeculoplasty (SLT) in eyes with early and more advanced stages of open angle glaucoma within 1 year of follow-up. Retrospective chart review in a consecutive series of patients treated by SLT to reduce intraocular pressure (IOP) or decrease number of topical medications in cases of discomfort and allergy. The cup-to-disc ratio of the optic nerve and the GSS 2 (glaucoma staging system 2) was used to differentiate between early (group 1) and more advanced (group 2) stages of glaucoma. At the time of SLT treatment, no new signs of glaucoma progression were seen. Only the first treated eye of every patient was included in the analysis. In group 1 (early glaucoma), 27 eyes were included. IOP reduction <21 mmHg/>20 % of the preoperative IOP-value and reduction of medication were achieved in 17 eyes (62.96 %). Successful re-treatment was necessary in 2 eyes (7.4 %). In group 2 (advanced glaucoma), 44 eyes underwent SLT. In eight eyes (18.18 %), filtrating surgery was necessary after initial SLT. In the remaining 36 eyes, IOP reduction <21 mmHg/>20 % of the baseline IOP was achieved in 26 eyes (59.09 % of 44 eyes) and IOP reduction <18 mmHg/> 30 % of the baseline IOP in 22 eyes (50 % of 44 eyes). SLT was safe and effective in nearly 2/3 of early glaucoma patients and also in 50 % of advanced glaucoma patients using stronger criteria of success. Failure of SLT in advanced glaucoma should lead to immediate filtrating surgery, which seems not to be associated with higher risk of fibrosis.

  16. Tag SNPs detect association of the CYP1B1 gene with primary open angle glaucoma

    PubMed Central

    Hewitt, Alex W.; Mackey, David A.; Mitchell, Paul; Craig, Jamie E.

    2010-01-01

    Purpose The cytochrome p450 family 1 subfamily B (CYP1B1) gene is a well known cause of autosomal recessive primary congenital glaucoma. It has also been postulated as a modifier of disease severity in primary open angle glaucoma (POAG), particularly in juvenile onset families. However, the role of common variation in the gene in relation to POAG has not been thoroughly explored. Methods Seven tag single nucleotide polymorphisms (SNPs), including two coding variants (L432V and N543S), were genotyped in 860 POAG cases and 898 examined normal controls. Each SNP and haplotype was assessed for association with disease. In addition, a subset of 396 severe cases and 452 elderly controls were analyzed separately. Results There was no association of any individual SNP in the full data set. Two SNPs (rs162562 and rs10916) were nominally associated under a dominant model in the severe cases (p<0.05). A common haplotype (AGCAGCC) was also found to be nominally associated in both the full data set (p=0.048, OR [95%CI]=0.83 [0.69–0.90]) and more significantly in the severe cases (p=0.004, OR [95%CI]=0.68 [0.52–0.89]) which survives correction for multiple testing. Conclusions Although no major effect of common variation at the CYP1B1 locus on POAG was found, there could be an effect of SNPs tagged by rs162562 and represented on the AGCAGCC haplotype. PMID:21139974

  17. [Effects of nootropic agents on visual functions and lacrimal antioxidative activity in patients with primary open-angle glaucoma].

    PubMed

    Davydova, N G; Kuznetsova, T P; Borisova, S A; Abdulkadyrova, M Zh

    2006-01-01

    The paper presents the results of an investigation of the effect of the nootropic agents pantogam and nooclerine on visual functions in patients with primary open-angle glaucoma. These agents have been found to have a beneficial effect on the functional activity of the retina and optic nerve, light sensitivity, hemo- and hydrodynamics of the eye.

  18. Longitudinal Analysis of Serum Autoantibody-Reactivities in Patients with Primary Open Angle Glaucoma and Optic Disc Hemorrhage

    PubMed Central

    Keilani, Munir M.; Wasielica-Poslednik, Joanna; Pfeiffer, Norbert; Grus, Franz H.

    2016-01-01

    Background The aim of our current investigation was to analyze the autoantibody-reactivities of primary open angle glaucoma patients with optic disc hemorrhage as possibly correlated to disease progression by means of a protein microarray approach. Methods Sera of patients with primary open angle glaucoma and optic disc hemorrhage (n = 16) were collected directly after study inclusion (0 weeks) and after 2 weeks, 4 weeks and 12 weeks. As a control group patients with primary open angle glaucoma (n = 18) were used (0 weeks and 12 weeks). Microarrays were incubated and occurring antibody-antigen-reactions were visualized with fluorescence labeled anti-human-IgG secondary antibodies. To detect changes in autoantibodies spot intensities were digitized and compared. Results With respect to the immunoreactivity at 0 weeks level increment of anti-adaptor protein 1 complex subunit mu-1 antibodies and anti-SPRY domain-containing SOCS box protein 3 antibodies in sera of primary open angle patients with optic disc hemorrhage was detected. Linear trend analysis revealed a positive correlation with r ≥ 0.8 between antibody-level and time course. Control group show no relevant changes in the same period. Significant changes were found in time point 4 comparison between patient groups in anti-adaptor protein 1 complex subunit mu-1-level (p = 0.01). No significant changes in visual acuity were found. Conclusion With this approach we were able to detect autoimmune reactivities in sera of patients with primary open angle glaucoma and optic disc hemorrhage compared to patients without optic disc hemorrhage. These antibodies could give further insights into the pathogenesis and the autoimmune component of glaucomatous optic neuropathy. PMID:28030545

  19. Association of primary open-angle glaucoma with mitochondrial variants and haplogroups common in African Americans

    PubMed Central

    Gudiseva, Harini V.; Trachtman, Benjamin; Bowman, Anita S.; Sagaser, Anna; Sankar, Prithvi; Miller-Ellis, Eydie; Lehman, Amanda; Addis, Victoria; O'Brien, Joan M.

    2016-01-01

    Purpose To estimate the population frequencies of all common mitochondrial variants and ancestral haplogroups among 1,999 subjects recruited for the Primary Open-Angle African American Glaucoma Genetics (POAAGG) Study, including 1,217 primary open-angle glaucoma (POAG) cases and 782 controls, and to identify ancestral subpopulations and mitochondrial mutations as potential risk factors for POAG susceptibility. Methods Subject classification by characteristic glaucomatous optic nerve findings and corresponding visual field defects, as defined by enrolling glaucoma specialists, stereo disc photography, phlebotomy, extraction of total DNA from peripheral blood or saliva, DNA quantification and normalization, PCR amplification of whole mitochondrial genomes, Ion Torrent deep semiconductor DNA sequencing on DNA pools (“Pool-seq”), Sanger sequencing of 3,479 individual mitochondrial DNAs, and bioinformatic analysis. Results The distribution of common African haplogroups within the POAAGG study population was broadly similar to prior surveys of African Americans. However, the POAG case population was found to be enriched in L1c2 haplogroups, which are defined in part by missense mutations m.6150G>A (Val83Ile, odds ratio [OR] 1.8, p=0.01), m.6253C>T (Met117Thr, rs200165736, OR 1.6, p=0.04), and m.6480G>A (Val193Ile, rs199476128, OR 4.6, p=0.04) in the cytochrome c oxidase subunit 1 (MT-CO1) gene and by a variant, m.2220A>G (OR 2.0, p=0.01), in MT-RNR2, which encodes the mitochondrial ribosomal 16s RNA gene. L2 haplogroups were predicted to be overrepresented in the POAG case population by Pool-seq, and the difference was confirmed to be significant with Sanger sequencing, that targeted the L2-associated variants m.2416T>C (rs28358580, OR 1.2, p=0.02) and m.2332C>T (OR 1.2, p=.02) in MT-RNR2. Another variant within MT-RNR2, m.3010G>A (rs3928306), previously implicated in sensitivity to the optic neuropathy-associated antibiotic linezolid, and arising on D4 and J1

  20. Discovery and Functional Annotation of SIX6 Variants in Primary Open-Angle Glaucoma

    PubMed Central

    Allingham, R. Rand; Whigham, Benjamin T.; Havens, Shane; Garrett, Melanie E.; Qiao, Chunyan; Katsanis, Nicholas; Wiggs, Janey L.; Pasquale, Louis R.; Ashley-Koch, Allison; Oh, Edwin C.; Hauser, Michael A.

    2014-01-01

    Glaucoma is a leading cause of blindness worldwide. Primary open-angle glaucoma (POAG) is the most common subtype and is a complex trait with multigenic inheritance. Genome-wide association studies have previously identified a significant association between POAG and the SIX6 locus (rs10483727, odds ratio (OR) = 1.32, p = 3.87×10−11). SIX6 plays a role in ocular development and has been associated with the morphology of the optic nerve. We sequenced the SIX6 coding and regulatory regions in 262 POAG cases and 256 controls and identified six nonsynonymous coding variants, including five rare and one common variant, Asn141His (rs33912345), which was associated significantly with POAG (OR = 1.27, p = 4.2×10−10) in the NEIGHBOR/GLAUGEN datasets. These variants were tested in an in vivo Danio rerio (zebrafish) complementation assay to evaluate ocular metrics such as eye size and optic nerve structure. Five variants, found primarily in POAG cases, were hypomorphic or null, while the sixth variant, found only in controls, was benign. One variant in the SIX6 enhancer increased expression of SIX6 and disrupted its regulation. Finally, to our knowledge for the first time, we have identified a clinical feature in POAG patients that appears to be dependent upon SIX6 genotype: patients who are homozygous for the SIX6 risk allele (His141) have a statistically thinner retinal nerve fiber layer than patients homozygous for the SIX6 non-risk allele (Asn141). Our results, in combination with previous SIX6 work, lead us to hypothesize that SIX6 risk variants disrupt the development of the neural retina, leading to a reduced number of retinal ganglion cells, thereby increasing the risk of glaucoma-associated vision loss. PMID:24875647

  1. Primary Open Angle Glaucoma is Associated with MR Biomarkers of Cerebral Small Vessel Disease

    PubMed Central

    Mercieca, Karl; Cain, John; Hansen, Thomas; Steeples, Laura; Watkins, Amy; Spencer, Fiona; Jackson, Alan

    2016-01-01

    This prospective study tests the hypotheses that: 1) glaucoma is associated with evidence of cerebral small vessel disease; 2) that imaging biomarkers of cerebral small vessel disease in POAG and NTG will show different characteristics. 12 normal controls, 7 patients with primary open angle glaucoma (POAG) and 9 patients with normal tension glaucoma (NTG) were recruited. Ophthalmological clinical assessment and MR imaging of the brain were performed. MR imaging was used to quantify white matter lesion load, frequency of dilated perivascular spaces (PVS) and abnormalities in cerebral hydrodynamics. Patients with POAG had significantly greater white matter lesion load (p < 0.05), more PVS in the centrum semiovale (p < 0.05) and had higher overall PVS scores than controls (p < 0.05). In the POAG group, optic cup-to-disc ratio (CDR) was positively correlated with deep white matter hyperintensities (R2 = 0.928, p < 0.01). Mean deviation on the Humphrey visual field assessment was negatively correlated with deep white matter lesion load (R2 = −0.840, p < 0.01), total white matter lesion load (R2 = −0.928, p < 0.01) and total PVS (R2 = −0.820, p < 0.01). MR evidence of cerebral small vessel disease is strongly associated with a diagnosis of POAG and with the severity of abnormalities in CDR and visual field. PMID:26923106

  2. Comparison of Prelaminar Thickness between Primary Open Angle Glaucoma and Normal Tension Glaucoma Patients

    PubMed Central

    Jung, Youn Hea; Park, Hae-Young L.; Jung, Kyoung In; Park, Chan Kee

    2015-01-01

    Main Objective The thinning of prelaminar tissue and prelamina cupping is known to occur by ischemia, as we see in anterior ischemic optic neuropathy. Since normal tension glaucoma (NTG) is thought to be more related to vascular factor than in primary open-angle glaucoma (POAG), we hypothesized that prelamina thinning may occur prominently in NTG patients. This study investigated the difference in prelaminar tissue thickness between patients with POAG and NTG and verified the factors related to prelaminar thinning. Methods Complete ophthalmic examination including standard automatic perimetry was performed in all patients. The prelaminar tissue thickness was measured in all patients by performing enhanced depth imaging with a Heidelberg Spectralis Optical Coherence Tomography. The retinal nerve fiber layer and optic nerve head parameters were obtained using the Heidelberg Retina Tomography II and Cirrus Optical Coherence Tomography. Various ocular factors and their relationships with prelaminar thickness were analyzed. Results The mean prelaminar tissue thickness was significantly thinner in patients with POAG than in those with NTG. The difference in the prelaminar thickness between patients with POAG and those with NTG was greater in the early field defect group than in the moderate and severe field groups. In multivariate analysis, the mean prelaminar thickness was related to the intraocular pressure, mean deviation, cup-disc ratio, and cup volume. Conclusions The prelaminar tissue was thinner in patients with POAG than in patients with NTG, and intraocular pressure had a strong influence on the prelaminar thickness in both POAG and NTG. This may indicate that mechanical compression is the main pathogenic factor in both POAG and NTG. PMID:25793734

  3. Stab Incision Glaucoma Surgery: A Modified Guarded Filtration Procedure for Primary Open Angle Glaucoma

    PubMed Central

    Jacob, Soosan; Figus, Michele; Ashok Kumar, Dhivya; Areeckal Incy, Saijimol

    2016-01-01

    Purpose. To describe a modified guarded filtration surgery, stab incision glaucoma surgery (SIGS), for primary open angle glaucoma (POAG). Methods. This prospective, interventional case series included patients with POAG (IOP ≥21 mmHg with glaucomatous visual field defects). After sliding superior conjunctiva down over limbus, 2.8 mm bevel-up keratome was used to create conjunctival entry and superficial corneoscleral tunnel in a single step starting 1.5 mm behind limbus. Lamellar corneoscleral tunnel was carefully dissected 0.5–1 mm into cornea and anterior chamber (AC) was entered. Kelly Descemet's punch (1 mm) was slid along the tunnel into AC to punch internal lip of the tunnel, thereby compromising it. Patency of ostium was assessed by injecting fluid in AC and visualizing leakage from tunnel. Conjunctival incision alone was sutured. Results. Mean preoperative IOP was 27.41 ± 5.54 mmHg and mean postoperative IOP was 16.47 ± 4.81 mmHg (n = 17). Mean reduction in IOP was 38.81 ± 16.55%. There was significant reduction of IOP (p < 0.000). 64.7% had IOP at final follow-up of <18 mmHg without medication and 82.35% had IOP <18 mmHg with ≤2 medications. No sight threatening complications were encountered. Conclusion. Satisfactory IOP control was noted after SIGS in interim follow-up (14.18 ± 1.88 months). PMID:27144015

  4. Stab Incision Glaucoma Surgery: A Modified Guarded Filtration Procedure for Primary Open Angle Glaucoma.

    PubMed

    Jacob, Soosan; Figus, Michele; Ashok Kumar, Dhivya; Agarwal, Ashvin; Agarwal, Amar; Areeckal Incy, Saijimol

    2016-01-01

    Purpose. To describe a modified guarded filtration surgery, stab incision glaucoma surgery (SIGS), for primary open angle glaucoma (POAG). Methods. This prospective, interventional case series included patients with POAG (IOP ≥21 mmHg with glaucomatous visual field defects). After sliding superior conjunctiva down over limbus, 2.8 mm bevel-up keratome was used to create conjunctival entry and superficial corneoscleral tunnel in a single step starting 1.5 mm behind limbus. Lamellar corneoscleral tunnel was carefully dissected 0.5-1 mm into cornea and anterior chamber (AC) was entered. Kelly Descemet's punch (1 mm) was slid along the tunnel into AC to punch internal lip of the tunnel, thereby compromising it. Patency of ostium was assessed by injecting fluid in AC and visualizing leakage from tunnel. Conjunctival incision alone was sutured. Results. Mean preoperative IOP was 27.41 ± 5.54 mmHg and mean postoperative IOP was 16.47 ± 4.81 mmHg (n = 17). Mean reduction in IOP was 38.81 ± 16.55%. There was significant reduction of IOP (p < 0.000). 64.7% had IOP at final follow-up of <18 mmHg without medication and 82.35% had IOP <18 mmHg with ≤2 medications. No sight threatening complications were encountered. Conclusion. Satisfactory IOP control was noted after SIGS in interim follow-up (14.18 ± 1.88 months).

  5. Oxygen saturation measurements of the retinal vasculature in treated asymmetrical primary open-angle glaucoma using hyperspectral imaging

    PubMed Central

    Mordant, D J; Al-Abboud, I; Muyo, G; Gorman, A; Harvey, A R; McNaught, A I

    2014-01-01

    Purpose To determine whether there are differences in retinal vascular oxygen saturation measurements, estimated using a hyperspectral fundus camera, between normal eyes and treated eyes of subjects with asymmetrical primary open-angle glaucoma (POAG). Methods A noninvasive hyperspectral fundus camera was used to acquire spectral images of the retina at wavelengths between 556 and 650 nm in 2-nm increments. In total, 14 normal eyes and both eyes of 11 treated POAG subjects were imaged and analyzed using algorithms that use the spectral variation of the optical densities of blood vessels to estimate the oxygen saturation of blood within the retinal vasculature. In the treated POAG group, each of the eyes were categorized, based on the mean deviation of the Humphrey visual-field analyzer result, as either more-advanced or less-advanced, glaucomatous eyes. Unpaired t-tests (two-tailed) with Welch's correction were used to compare the mean oxygen saturation between the normal subjects and the treated POAG subgroups. Results In less-advanced and more-advanced-treated POAG eyes, mean retinal venular oxygen saturations (48.2±21.6% and 42.6±18.8%, respectively) were significantly higher than in normal eyes (27.9±9.9% P=0.03 and 0.01, respectively). Arteriolar oxygen saturation was not significantly different between normal eyes and treated POAG eyes. Conclusions The increased oxygen saturation of the retinal venules in advanced-treated POAG eyes may indicate reduced metabolic consumption of oxygen in the inner retinal tissues. PMID:25060843

  6. Phacoemulsification combined with deep sclerectomy augmented with mitomycin and amniotic membrane implantation in chronic primary open angle glaucoma with cataract

    PubMed Central

    Helmy, Hazem

    2016-01-01

    Objective The aim of this study was to determine the safety and efficacy of combined phacoemulsification plus Intraocular lens (IOL) implantation with deep sclerectomy augmented with mitomycin C (MMC) and sub-flap implantation of amniotic membrane for the management of uncontrolled, chronic, primary open-angle glaucoma patients. Methods This prospective study included 41 patients with chronic, primary, open-angle glaucoma and cataract uncontrolled with medical treatment who underwent combined phacoemulsification augmented with mitomycin C (MMC) application and amniotic membrane implantation under the scleral flap. Intraocular pressure (IOP), visual acuity, glaucoma medications, stabilization of visual field, complications, and viability of the success rate were assessed a 36-month follow-up period. Results The mean age of cases was 54.8 ± 5.3 years. Sixty-one percent of cases were males, and 39% were females. The mean IOP decreased from 23.8 ± 1.8 mmHg preoperatively to 16.8 ± 2.3 mmHg postoperatively. The overall success rate was 97.5, 95, and 92.7% in the first, second, and third year, respectively. The overall success rate was 90% in the first year, but that decreased to 85.3 and 78% in the second and third year, respectively. Qualified success was 7.5, 10, and 14.7% in the first, second, and third year, respectively. Failure was recorded as 2.5, 5, and 7.3% in the first, second, and third year, respectively. IOP reduction was sustained through the follow-up period. Visual acuity improved from 0.13 ± 0.06 to 0.9 ± 0.07 (p < 0.001). The visual field improved significantly in the first assessment, from 14.0 ± 2.7 preoperatively to 12.6 ± 2.6 at three months postoperatively (p < 0.001), after which it became stable for the remainder of the follow-up period. One hundred percent of cases were on three anti-glaucoma drugs preoperatively, while postoperatively, 12.2% were on three drugs, 4.2% were on two drugs, and 82.9% were controlled without anti

  7. Common variants near ABCA1, AFAP1 and GMDS confer risk of primary open-angle glaucoma

    PubMed Central

    Fogarty, Rhys; Sharma, Shiwani; Hewitt, Alex W.; Martin, Sarah; Law, Matthew H.; Cremin, Katie; Bailey, Jessica N. Cooke; Loomis, Stephanie J.; Pasquale, Louis R.; Haines, Jonathan L.; Hauser, Michael A.; Viswanathan, Ananth C.; McGuffin, Peter; Topouzis, Fotis; Foster, Paul J.; Graham, Stuart L; Casson, Robert J; Chehade, Mark; White, Andrew J; Zhou, Tiger; Souzeau, Emmanuelle; Landers, John; Fitzgerald, Jude T; Klebe, Sonja; Ruddle, Jonathan B; Goldberg, Ivan; Healey, Paul R; Mills, Richard A.; Wang, Jie Jin; Montgomery, Grant W.; Martin, Nicholas G.; Radford-Smith, Graham; Whiteman, David C.; Brown, Matthew A.; Wiggs, Janey L.; Mackey, David A; Mitchell, Paul; MacGregor, Stuart; Craig, Jamie E.

    2014-01-01

    Primary open-angle glaucoma (POAG) is a major cause of irreversible blindness worldwide. We performed a genome-wide association study in an Australian discovery cohort comprising 1,155 advanced POAG cases and 1,992 controls. Association of the top SNPs from the discovery stage was investigated in two Australian replication cohorts (total 932 cases, 6,862 controls) and two US replication cohorts (total 2,616 cases, 2,634 controls). Meta-analysis of all cohorts revealed three novel loci associated with development of POAG. These loci are located upstream of ABCA1 (rs2472493 [G] OR=1.31, P= 2.1 × 10−19), within AFAP1 (rs4619890 [G] OR=1.20, P= 7.0 × 10−10) and within GMDS (rs11969985 [G] OR=1.31, and P= 7.7 × 10−10). Using RT-PCR and immunolabelling, we also showed that these genes are expressed within human retina, optic nerve and trabecular meshwork and that ABCA1 and AFAP1 are also expressed in retinal ganglion cells. PMID:25173105

  8. Evaluation of Contrast Sensitivity, Chromatic Vision, and Reading Ability in Patients with Primary Open Angle Glaucoma

    PubMed Central

    Güerri, Noemi; Cameo, Beatriz; Polo, Vicente; Larrosa, Jose M.

    2016-01-01

    Purpose. To compare contrast sensitivity, acquired color vision deficiency, and reading ability in patients with glaucoma at different stages of the disease and to establish correlations between visual field parameters and visual function scores. Methods. This prospective cross-sectional study included 121 glaucoma patients. Subjects with a diagnosis of chronic open angle glaucoma were recruited and classified according to Hodapp-Parrish-Anderson criteria. Patients with severe visual field defects were excluded because they were older, which could bias the interpretation of visual function tests. Contrast sensitivity was measured using the Pelli-Robson Chart and the CSV1000E test. Chromatic vision was evaluated using the Farnsworth-panel D15 and the L'Anthony D15 tests of Vision Color Recorder software. Reading ability was measured using Radner-Vissum test. Results. Contrast sensitivity (with photopic and mesopic luminance with glare) differed significantly between patients with early and moderate visual field defects (p < 0.05). Reading ability scores and results of the chromatic vision tests did not differ significantly between the two groups. Significant and moderate Spearman correlations between visual field indexes and contrast sensitivity tests were detected. Conclusions. Contrast sensitivity was significantly worse in patients with moderate glaucoma compared to those with early-stage glaucoma. Evaluation of visual function in clinical practice provides important information to address a glaucoma patient's vision complaints. PMID:27872754

  9. Intraocular pressure fluctuation after water drinking test in primary angle-closure glaucoma and primary open-angle glaucoma

    PubMed Central

    Poon, Yi-Chieh; Teng, Mei-Ching; Lin, Pei-Wen; Tsai, Jen-Chia; Lai, Ing-Chou

    2016-01-01

    Context: Only a few studies have assessed intraocular pressure (IOP) changes during the water drinking test (WDT) in patients with primary angle-closure glaucoma (PACG). Aims: The aim of this study is to investigate IOP changes during WDT in patients with PACG versus primary open-angle glaucoma (POAG). Settings and Design: This was a prospective and single tertiary center study. Materials and Methods: PACG and POAG patients (n = 15 each) without prior glaucoma surgery were enrolled and subjected to WDT, wherein they consumed an amount of water proportional to their body weight within 10 min. IOP was measured at baseline and every 15 min for 1 h after water intake. Statistical Analysis Used: Intergroup comparisons were performed using Mann–Whitney U-test for continuous variables and Chi-square test for categorical variables. Wilcoxon signed-ranks test was used for comparisons of IOP before and after water intake in the two groups. Regression analysis was used to determine factors associated with IOP fluctuations during WDT. Results: IOP changes over 1 h after water intake showed no significant differences between groups. The mean maximum fluctuation from baseline was 3.61 ± 2.49 and 3.79 ± 1.91 mmHg, respectively, in the PACG and POAG groups. The mean peak IOP was 19.17 ± 4.32 and 19.87 ± 3.44 mmHg in the PACG and PAOG groups, respectively. The axial length and anterior chamber depth showed no correlations with IOP fluctuations. Conclusions: We found similar IOP fluctuation curves and peak IOP values in both PACG and POAG patients subjected to WDT. These findings suggest that WDT is a useful test to induce IOP peaks in both POAG and PACG patients. PMID:28112134

  10. A common gene for juvenile and adult-onset primary open-angle glaucomas confined on chromosome 1q

    SciTech Connect

    Morissette, J.; Plante, M.; Raymond, V.

    1995-06-01

    Primary open-angle glaucoma (POAG), which causes progressive loss of the visual fields, was subdivided into two groups according to age at onset: (1) chronic open-angle glaucoma (COAG) diagnosed after 40 years and (2) juvenile open-angle glaucoma (JOAG) diagnosed between 3 years of age and early adulthood. A JOAG gene (GLC1A) was recently mapped to chromosome 1q. We studied 142 members of a huge multigenerational French Canadian family affected with autosomal dominant POAG. Either JOAG or COAG was diagnosed with ocular hypertension (OHT), which may lead to POAG. To localize a common disease gene that might be responsible for both glaucoma subsets, we performed linkage analysis considering JOAG and COAG under the same phenotypic category. JOAG/COAG was tightly linked to seven microsatellite markers on chromosome 1q23-q25; a maximum lod score of 6.62 was obtained with AF-M278ye5. To refine the disease locus, we exploited a recombination mapping strategy based on a unique founder effect. The same characteristic haplotype, composed of 14 markers spanning 12 cM between loci D1S196 and D1S212, was recognized in all persons affected by JOAG, COAG, or OHT, but it did not occur in unaffected spouses and in normal family members >35 years of age, except for three obligatory carriers. Key combination events confined the disease region within a 9-cM interval between loci D1S445 and D1S416/D1S480. These observations demonstrate that the GLC1A gene is responsible for both adult-onset and juvenile glaucomas and suggest that the JOAG and COAG categories within this family may be part of a clinical continuum artificially divided at age 40 years. 49 refs., 4 figs., 2 tabs.

  11. Recent Developments in Understanding the Role of Aqueous Humor Outflow in Normal and Primary Open Angle Glaucoma

    PubMed Central

    Hann, Cheryl R.; Fautsch, Michael P.

    2015-01-01

    Primary open angle glaucoma (POAG) is the second leading cause of blindness in the world's rapidly aging population. POAG is characterized by progressive degeneration of neural structures in the posterior segment, often associated with a concomitant elevation of intraocular pressure. Changes in IOP are believed to be caused by a disruption in the normal outflow of aqueous humor. This article reviews recent research associated with normal and POAG aqueous humor outflow. Novel findings elucidating biochemical and pathological changes in the ocular tissues affected in POAG are presented. Stem cell research, identification of lymphatic markers, and increased use of mouse models give researchers exciting new tools to understand aqueous humor outflow, changes associated with POAG and identify underlying causes of the disease. PMID:26236568

  12. [The effect of parenteral citicoline on visual functions and life quality of patients with primary open-angle glaucoma].

    PubMed

    Frolov, M A; Gonchar, P A; Barashkov, V I; Kumar, V; Morozova, N S; Frolov, A M; Kazakova, K A

    2011-01-01

    The effect of nootropic drug citicoline on visual functions, perimetric indexes of static automated perimetry, morphometric characteristics of retinal tomography and life quality of patients with primary open-angle glaucoma (POAG) stage I-III and normalized intraocular pressure (IOP) was studied. 40 patients aged 46-78 years old with POAG stage I-III and normalized IOP were treated with citicoline. Among them there were 24 female and 16 male. The patients were divided into 2 equal groups--experimental and control. Patients of both groups were treated with intravenous citicoline for 10 days. The dose of citicoline in experimental group was 1000 mg/day, in control--500 mg/day. After treatment in both groups visual functions, perimetric indexes of static automated perimetry, morphometric characteristics of retinal tomography and life quality showed improvement. Citicoline has significant neuroprotective effect preventing apoptosis.

  13. Assessing the Association of Mitochondrial Genetic Variation With Primary Open-Angle Glaucoma Using Gene-Set Analyses

    PubMed Central

    Khawaja, Anthony P.; Cooke Bailey, Jessica N.; Kang, Jae Hee; Allingham, R. Rand; Hauser, Michael A.; Brilliant, Murray; Budenz, Donald L.; Christen, William G.; Fingert, John; Gaasterland, Douglas; Gaasterland, Terry; Kraft, Peter; Lee, Richard K.; Lichter, Paul R.; Liu, Yutao; Medeiros, Felipe; Moroi, Syoko E.; Richards, Julia E.; Realini, Tony; Ritch, Robert; Schuman, Joel S.; Scott, William K.; Singh, Kuldev; Sit, Arthur J.; Vollrath, Douglas; Wollstein, Gadi; Zack, Donald J.; Zhang, Kang; Pericak-Vance, Margaret; Weinreb, Robert N.; Haines, Jonathan L.; Pasquale, Louis R.; Wiggs, Janey L.

    2016-01-01

    Purpose Recent studies indicate that mitochondrial proteins may contribute to the pathogenesis of primary open-angle glaucoma (POAG). In this study, we examined the association between POAG and common variations in gene-encoding mitochondrial proteins. Methods We examined genetic data from 3430 POAG cases and 3108 controls derived from the combination of the GLAUGEN and NEIGHBOR studies. We constructed biological-system coherent mitochondrial nuclear-encoded protein gene-sets by intersecting the MitoCarta database with the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. We examined the mitochondrial gene-sets for association with POAG and with normal-tension glaucoma (NTG) and high-tension glaucoma (HTG) subsets using Pathway Analysis by Randomization Incorporating Structure. Results We identified 22 KEGG pathways with significant mitochondrial protein-encoding gene enrichment, belonging to six general biological classes. Among the pathway classes, mitochondrial lipid metabolism was associated with POAG overall (P = 0.013) and with NTG (P = 0.0006), and mitochondrial carbohydrate metabolism was associated with NTG (P = 0.030). Examining the individual KEGG pathway mitochondrial gene-sets, fatty acid elongation and synthesis and degradation of ketone bodies, both lipid metabolism pathways, were significantly associated with POAG (P = 0.005 and P = 0.002, respectively) and NTG (P = 0.0004 and P < 0.0001, respectively). Butanoate metabolism, a carbohydrate metabolism pathway, was significantly associated with POAG (P = 0.004), NTG (P = 0.001), and HTG (P = 0.010). Conclusions We present an effective approach for assessing the contributions of mitochondrial genetic variation to open-angle glaucoma. Our findings support a role for mitochondria in POAG pathogenesis and specifically point to lipid and carbohydrate metabolism pathways as being important. PMID:27661856

  14. Question on clinical efficiency and principles of diode laser radiation activity at a primary open-angle glaucoma

    NASA Astrophysics Data System (ADS)

    Bolshunov, A. V.; Litvinova, G. G.; Ilyina, O. S.; Easakiva, A. L.; Fyodorov, A. A.; Poleva, R. P.

    1999-07-01

    The efficiency of a diode laser with a wavelength 0,81 microns in treatment of an open-angle glaucoma is investigated. The diode LTP is a pathogenesis oriented method of treatment of an open angle glaucoma: it gives in improvement of outflow of an intraocular fluid, stabilization and improvement of visual functions for patients with initial and developed stages of disease at term of observation up to 12 months.

  15. Micro-Bypass Implantation for Primary Open-Angle Glaucoma Combined with Phacoemulsification: 4-Year Follow-Up

    PubMed Central

    Fea, Antonio Maria; Consolandi, Giulia; Zola, Marta; Pignata, Giulia; Cannizzo, Paola; Lavia, Carlo; Rolle, Teresa; Grignolo, Federico Maria

    2015-01-01

    Purpose. To report the long-term follow-up results in patients with cataract and primary open-angle glaucoma (POAG) randomly assigned to cataract surgery combined with micro-bypass stent implantation or phacoemulsification alone. Methods. 36 subjects with cataract and POAG were randomized in a 1 : 2 ratio to either iStent implantation and cataract surgery (combined group) or cataract surgery alone (control group). 24 subjects agreed to be evaluated again 48 months after surgery. Patients returned one month later for unmedicated washout assessment. Results. At the long-term follow-up visit we reported a mean IOP of 15,9 ± 2,3 mmHg in the iStent group and 17 ± 2,5 mmHg in the control group (p = NS). After washout, a 14,2% between group difference in favour of the combined group was statistically significant (p = 0,02) for mean IOP reduction. A significant reduction in the mean number of medications was observed in both groups compared to baseline values (p = 0,005 in the combined group and p = 0,01 in the control group). Conclusion. Patients in the combined group maintained low IOP levels after long-term follow-up. Cataract surgery alone showed a loss of efficacy in controlling IOP over time. Both treatments reduced the number of ocular hypotensive medications prescribed. This trial is registered with: NCT00847158. PMID:26587282

  16. Elevated Plasma Endothelin-1 Levels in Normal Tension Glaucoma and Primary Open-Angle Glaucoma: A Meta-Analysis

    PubMed Central

    Li, Shengjie; Zhang, Aiping

    2016-01-01

    Purpose. The aim of this meta-analysis was to clarify the association between the plasma endothelin-1 level and the risks of normal tension glaucoma (NTG) and primary open-angle glaucoma (POAG). Methods. Relevant publications were collected from three databases including PubMed, EMBASE, and the Web of Science through December 31, 2015. In this study, the terms “(endothelin OR ET) AND glaucoma” were searched. Review Manager 5.2 was used to process the data. Results. Seven studies (212 cases, 164 controls) were included for the NTG analysis. The mean plasma endothelin-1 level in the NTG subjects was 0.60 pg/mL (p = 0.02, 95% CI: 0.17–1.04) higher than that of the healthy controls. Six studies (160 cases, 174 controls) were included for the POAG analysis, and the endothelin-1 level was 0.63 pg/mL (p = 0.007, 95% CI: 0.12–1.15) higher in the POAG subjects than in the healthy controls. Additionally, two studies influenced the meta-analysis results regarding the association of plasma endothelin-1 with POAG by sensitivity analysis, and the probability of publication bias was low. Conclusions. The observation that NTG and POAG subjects showed significantly elevated endothelin-1 plasma concentrations suggests that a higher plasma level of endothelin-1 might increase the risk of NTG and POAG development. PMID:27965889

  17. Soluble Guanylate Cyclase α1–Deficient Mice: A Novel Murine Model for Primary Open Angle Glaucoma

    PubMed Central

    Buys, Emmanuel S.; Ko, Yu-Chieh; Alt, Clemens; Hayton, Sarah R.; Jones, Alexander; Tainsh, Laurel T.; Ren, Ruiyi; Giani, Andrea; Clerté, Maeva; Abernathy, Emma; Tainsh, Robert E. T.; Oh, Dong-Jin; Malhotra, Rajeev; Arora, Pankaj; de Waard, Nadine; Yu, Binglan; Turcotte, Raphael; Nathan, Daniel; Scherrer-Crosbie, Marielle; Loomis, Stephanie J.; Kang, Jae H.; Lin, Charles P.; Gong, Haiyan; Rhee, Douglas J.; Brouckaert, Peter; Wiggs, Janey L.; Gregory, Meredith S.; Pasquale, Louis R.; Bloch, Kenneth D.; Ksander, Bruce R.

    2013-01-01

    Primary open angle glaucoma (POAG) is a leading cause of blindness worldwide. The molecular signaling involved in the pathogenesis of POAG remains unknown. Here, we report that mice lacking the α1 subunit of the nitric oxide receptor soluble guanylate cyclase represent a novel and translatable animal model of POAG, characterized by thinning of the retinal nerve fiber layer and loss of optic nerve axons in the context of an open iridocorneal angle. The optic neuropathy associated with soluble guanylate cyclase α1–deficiency was accompanied by modestly increased intraocular pressure and retinal vascular dysfunction. Moreover, data from a candidate gene association study suggests that a variant in the locus containing the genes encoding for the α1 and β1 subunits of soluble guanylate cyclase is associated with POAG in patients presenting with initial paracentral vision loss, a disease subtype thought to be associated with vascular dysregulation. These findings provide new insights into the pathogenesis and genetics of POAG and suggest new therapeutic strategies for POAG. PMID:23527308

  18. Medical management of primary open-angle glaucoma: Best practices associated with enhanced patient compliance and persistency

    PubMed Central

    Kulkarni, Sadhana V; Damji, Karim F; Buys, Yvonne M

    2008-01-01

    Primary open angle glaucoma is a chronic optic neuropathy often requiring lifelong treatment. Patient compliance, adherence and persistence with therapy play a vital role in improved outcomes by reducing morbidity and the economic consequences that are associated with disease progression. A literature review including searches of The Cochrane Library, MEDLINE, PubMed, conference proceedings, and bibliographies of identified articles reveals the enormous public health burden in various populations due to the impact of glaucoma associated visual impairment on the overall quality of life eg, fear of blindness, inability to work in certain occupations, driving restrictions, motor vehicle accidents, falls, and general health status. Providing specific definitions for the frequently misunderstood terms “compliance, persistence and adherence” with reference to medication use is central not only for monitoring patients’ drug dosing histories and clinical outcomes but also for subsequent research. In this review article, a summary of the advantages/disadvantages including cost-effectiveness of various medical approaches to glaucoma treatment, techniques employed for measuring patient compliance and actual patient preferences for therapy are outlined. We conclude by identifying the key barriers to ongoing treatment and suggest some best practices to enhance compliance and persistence. PMID:19920977

  19. Association of Common Variants in eNOS Gene with Primary Open Angle Glaucoma: A Meta-Analysis

    PubMed Central

    Xiang, Yang; Dong, Yi; Li, Xuan; Tang, Xin

    2016-01-01

    Purpose. To clarify the association of endothelial nitric oxide synthase (eNOS) polymorphisms and primary open angle glaucoma (POAG). Methods. After a systematic literature search in the MEDLINE, EMBASE, and ISI Web of Science databases, all relevant studies evaluating the association between the polymorphisms (rs2070744 and rs1799983) of eNOS gene and POAG were screened and included. The pooled odds ratios (ORs) and the 95% confidence interval (CI) of each single-nucleotide polymorphism (SNP) in five genetic models were estimated using fixed-effect model if I2 < 50% in the test for heterogeneity; otherwise the random-effects model was used. Results. Thirty-one records were obtained, with five being suitable for meta-analysis. The overall results showed that both TT genotype in rs2070744 and GG genotype in rs1799983 are associated with decreased risk of POAG susceptibility. Stratified analysis based on ethnicity showed that the association of rs2070744 with POAG remained only in Caucasians. Results of subgroup analysis by sex indicated association between both polymorphisms and POAG in female group, but not in male group. Conclusions. TT genotype and/or T-allele in rs2070744, as well as GG genotype and/or G-allele in rs1799983, was associated with decreased risk for POAG overall and in female group. PMID:27242919

  20. Predicting Clinical Binary Outcome Using Multivariate Longitudinal Data: Application to Patients with Newly Diagnosed Primary Open-Angle Glaucoma.

    PubMed

    Gao, Feng; Miller, J Philip; Beiser, Julia A; Xiong, Chengjie; Gordon, Mae O

    2015-10-01

    Primary open angle glaucoma (POAG) is a chronic, progressive, irreversible, and potentially blinding optic neuropathy. The risk of blindness due to progressive visual field (VF) loss varies substantially from patient to patient. Early identification of those patients destined to rapid progressive visual loss is crucial to prevent further damage. In this article, a latent class growth model (LCGM) was developed to predict the binary outcome of VF progression using longitudinal mean deviation (MD) and pattern standard deviation (PSD). Specifically, the trajectories of MD and PSD were summarized by a functional principal component (FPC) analysis, and the estimated FPC scores were used to identify subgroups (latent classes) of individuals with distinct patterns of MD and PSD trajectories. Probability of VF progression for an individual was then estimated as weighted average across latent classes, weighted by posterior probability of class membership given baseline covariates and longitudinal MD/PSD series. The model was applied to the participants with newly diagnosed POAG from the Ocular Hypertension Treatment Study (OHTS), and the OHTS data was best fit by a model with 4 latent classes. Using the resultant optimal LCGM, the OHTS participants with and without VF progression could be accurately differentiated by incorporating longitudinal MD and PSD.

  1. Fluctuation in systolic blood pressure is a major systemic risk factor for development of primary open-angle glaucoma

    PubMed Central

    Lee, Na Young; Jung, Younhea; Han, Kyungdo; Park, Chan Kee

    2017-01-01

    We evaluated the risk of development of primary open-angle glaucoma (POAG) in terms of variability in BP using a nationwide, population-based, 11-year longitudinal study using the Korean National Health Insurance Research Database. We included patients who underwent health care examinations more than twice between January 2002 and December 2006. We divided all subjects by the quartiles of variability in systolic blood pressure (SBP), diastolic blood pressure (DBP), and the difference between SBP and DBP. Of the total of 80,021 included subjects, 910 were diagnosed with POAG between January 2007 and December 2013. Both the Kaplan-Meier survival curves and log-rank test data indicated that patients with higher-level BP variability developed POAG significantly more frequently than did patients with lower-level variability (P < 0.001). On multivariate Cox’s regression modeling including gender, age, sex, household income, smoking status, level of alcohol intake, extent of exercise, diabetes mellitus status, dyslipidemia status, SBP, and DBP; the hazard ratios among the highest and lowest quartiles of SD SBP and CV SBP were 1.256 and 1.238, respectively. Our findings suggest that subjects in the highest quartile of SBP variability were significantly more likely to develop POAG in our population-based sample of Korean adults. PMID:28262703

  2. Expression profile of the matricellular protein osteopontin in primary open-angle glaucoma and the normal human eye.

    PubMed

    Chowdhury, Uttio Roy; Jea, Seung-Youn; Oh, Dong-Jin; Rhee, Douglas J; Fautsch, Michael P

    2011-08-16

    PURPOSE. To characterize the role of osteopontin (OPN) in primary open-angle glaucoma (POAG) and normal eyes. METHODS. OPN quantification was performed by enzyme-linked immunosorbent assay in aqueous humor (AH) obtained from human donor eyes (POAG and normal) and surgical samples (POAG and elective cataract removal). OPN expression and localization in whole eye tissue sections and primary normal human trabecular meshwork (NTM) cells were studied by Western blot and immunohistochemistry. Latanoprost-free acid (LFA)-treated NTM cells were analyzed for OPN gene and protein expression. Intraocular pressure was measured by tonometry, and central corneal thickness was measured by optical coherence tomography in young OPN(-/-) and wild-type mice. RESULTS. OPN levels were significantly reduced in donor POAG AH compared with normal AH (0.54 ± 0.18 ng/μg [n = 8] vs. 0.77 ± 0.23 ng/μg [n = 9]; P = 0.039). A similar trend was observed in surgical AH (1.05 ± 0.31 ng/μg [n = 20] vs. 1.43 ± 0.88 ng/μg [n = 20]; P = 0.083). OPN was present in the trabecular meshwork, corneal epithelium and endothelium, iris, ciliary body, retina, vitreous humor, and optic nerve. LFA increased OPN gene expression, but minimal change in OPN protein expression was observed. No difference in intraocular pressure (17.5 ± 2.0 mm Hg [n = 56] vs. 17.3 ± 1.9 mm Hg [n = 68]) but thinner central corneal thickness (91.7 ± 3.6 μm [n = 50] vs. 99.2 ± 5.5 μm [n = 70]) was noted between OPN(-/-) and wild-type mice. CONCLUSIONS. OPN is widely distributed in the human eye and was found in lower concentrations in POAG AH. Reduction of OPN in young mice does not affect IOP.

  3. Early Postoperative Effects of Cataract Surgery on Anterior Segment Parameters in Primary Open-Angle Glaucoma and Pseudoexfoliation Glaucoma

    PubMed Central

    Elgin, Ufuk; Şen, Emine; Şimşek, Tülay; Tekin, Kemal; Yılmazbaş, Pelin

    2016-01-01

    Objectives: To compare the effect of cataract surgery on anterior segment parameters measured by optical biometry in primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (PXG). Materials and Methods: Twenty-five eyes of 25 patients with POAG and 29 eyes of 29 patients with PXG who had uncomplicated phacoemulsification and posterior chamber intraocular lens implantation surgery were included to our prospective study. Central corneal thickness (CCT), anterior chamber depth (ACD) and axial length (AL) were measured with an optical biometer preoperatively and at 1 month postoperatively. The pre- and postoperative values of intraocular pressure (IOP) and the anterior segment parameters and the differences between POAG and PXG were compared statistically by paired t, independent t and chi-square tests. Results: The mean values of preoperative CCT (p=0.042) and ACD (p=0.012) were significantly lower in the PXG than in the POAG group. In the PXG group, IOP decreased (p=0.001) but CCT (p=0.03) and ACD (p=0.001) increased significantly postoperatively; AL did not change significantly. In the POAG group, IOP decreased (p=0.01) and ACD (p=0.004) increased significantly postoperatively, while AL and CCT did not change significantly. There were no significant differences in the pre- to postoperative changes in IOP (p=0.76), AL (p=0.44) and CCT (p=0.52) values between the two groups. However, the postoperative increase in ACD was larger in the PXG group (p=0.03). Conclusion: Cataract surgery may cause some changes in IOP and anterior segment parameters like ACD and CCT postoperatively in eyes with POAG and PXG, and these changes may differ between eyes with PXG and POAG. PMID:27800269

  4. Estimated Cerebrospina Fluid Pressure and the 5-Year Incidence of Primary Open-Angle Glaucoma in a Chinese Population

    PubMed Central

    Zhong, Hua; Tao, Yijin; Yuan, Yuansheng; Pan, Chen-Wei

    2016-01-01

    Purpose We aim to assess the longitudinal association between baseline estimated cerebrospinal fluid pressure (CSFP) and 5-year incident primary open angle glaucoma (POAG) in a population-based sample of Bai Chinese living in rural China. Methods Among the 2133 Bai Chinese aged 50 years or older who had participated in the baseline examination of the Yunnan Minority Eye Study, 1520 (71.3%) attended the follow-up examination after five years and 1485 were at risk of developing POAG. Participants underwent comprehensive ophthalmic examinations at both baseline and follow-up surveys. CSFP in mmHg was estimated as 0.55 × body mass index (kg/m2) + 0.16 × diastolic blood pressure (mmHg)-0.18 × age (years)-1.91. Glaucoma was defined using the International Society of Geographical and Epidemiological Ophthalmology Classification criteria. Multivariate logistic regression models were established to determine the association between baseline CSFP and incident POAG. Results After a mean follow-up time of 5 years, 19 new cases of POAG were detected, with an incidence rate of 1.3% (95% confidence interval, 0.7–1.9%). In multivariate logistic regression analysis, after adjusting for age, gender, education, intraocular pressure, central corneal thickness, hypertension and diabetes, no significant associations, nor any trends, were evident between baseline estimated CSFP and incident POAG. The association between estimated CSFP per mmHg increase in baseline and 5-year incidence of POAG was also non-significant, with adjusted relative risk of 0.96 (P = 0.11) in multivariate analysis. Conclusions This longitudinal cohort study does not support previously observed cross-sectional association between estimated CSFP and POAG in population-based studies. PMID:27611879

  5. Linkage analysis of primary open-angle glaucoma excludes the juvenile glaucoma region on chromosome 1q

    SciTech Connect

    Wirtz, M.K.; Acott, T.S.; Samples, J.R. |

    1994-09-01

    The gene for one form of juvenile glaucoma has been mapped to chromosome 1q21-q31. This raises the possibility of primary open-angle glaucoma (POAG) also mapping to this region if the same defective gene causes both diseases. To ask this question linkage analysis was performed on a large POAG kindred. Blood samples or skin biopsies were obtained from 40 members of this family. Individuals were diagnosed as having POAG if they met two or more of the following criteria: (1) Visual field defects compatible with glaucoma on automated perimetry; (2) Optic nerve head and/or nerve fiber layer analysis compatible with glaucomatous damage; (3) high intraocular pressures (> 20 mm Hg). Patients were considered glaucoma suspects if they only met one criterion. These individuals were excluded from the analysis. Of the 40 members, seven were diagnosed with POAG; four were termed suspects. The earliest age of onset was 38 years old, while the average age of onset was 65 years old. We performed two-point and multipoint linkage analysis, using five markers which encompass the region 1q21-q31; specifically, D1S194, D1S210, D1S212, D1S191 and LAMB2. Two-point lod scores excluded tight linkage with all markers except D1S212 (maximum lod score of 1.07 at theta = 0.0). In the multipoint analysis, including D1S210-D1S212-LAMB2 and POAG, the entire 11 cM region spanned by these markers was excluded for linkage with POAG; that is, lod scores were < -2.0. In conclusion, POAG in this family does not map to chromosome 1q21-q31 and, thus, they carry a gene that is distinct from the juvenile glaucoma gene.

  6. Comparison of Pattern Electroretinography and Optical Coherence Tomography Parameters in Patients with Primary Open-Angle Glaucoma and Ocular Hypertension

    PubMed Central

    Tiryaki Demir, Semra; Oba, Mehmet Ersin; Erdoğan, Ezgi Tuna; Odabaşı, Mahmut; Dirim, Ayşe Burcu; Demir, Mehmet; Can, Efe; Kara, Orhan; Yekta Şendül, Selam

    2015-01-01

    Objectives: To investigate the correlation of visual field (VF), pattern electroretinography (PERG) and Fourier domain optical coherence tomography (FD-OCT) results in patients with ocular hypertension (OHT) and early primary open-angle glaucoma (POAG). Materials and Methods: The study included 72 eyes of 37 patients with early POAG, 76 eyes of 38 patients with OHT, and 60 eyes of 30 controls. All subjects underwent full ophthalmologic examination, VF assessment with 24-2 Humphrey standard automated perimetry (Swedish Interactive Thresholding Algorithm (SITA)-Standard), retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thickness measurement with FD-OCT, and PERG P50 and N95 wave latency and amplitude measurements with electroretinography (Nihon Kohden). Results: With the exception of the nasal quadrant, all GCC parameters and RNFL results were significantly lower in the POAG group compared to the OHT and control groups. There was no statistically significant difference between the OHT and control group. PERG amplitudes were lower in the POAG and OHT groups than in the control group. Reduction in N95 amplitude was greater than that of P50 amplitude. No difference was detected in PERG latencies among groups. GCC was significantly correlated with VF and RNFL in the POAG group. Conclusion: Significant thinning of the GCC and RNFL occurs in addition to VF pathologies in patients with early POAG, and these examinations should be concomitantly evaluated. During diagnostic assessment of patients with early POAG, GCC and RNFL analysis by FD-OCT are highly effective. GCC is as reliable as RNLF in the early diagnosis of glaucoma and there is a highly significant correlation between them. Dysfunction of ganglion cells in patients with OHT may be detected earlier using PERG amplitude analysis. PMID:27800239

  7. Color Doppler Imaging Analysis of Retrobulbar Blood Flow Velocities in Primary Open-Angle Glaucomatous Eyes: A Meta-Analysis

    PubMed Central

    Meng, Nana; Zhang, Ping; Huang, Huadong; Ma, Jinlan; Zhang, Yue; Li, Hao; Qu, Yi

    2013-01-01

    Background To analyze the diagnostic value of color Doppler imaging (CDI) of blood flow in the retrobulbar vessels of eyes with primary open-angle glaucoma (POAG). Methods Pertinent publications were retrieved from the Cochrane Central Register of Controlled Trials, PubMed and the ISI Web of Knowledge up to October 2012. Changes in peak systolic velocity (PSV), end diastolic velocity (EDV) and resistive index (RI) of the ophthalmic artery (OA), central retinal artery (CRA) and short posterior ciliary artery (SPCA) of POAG eyes and normal controls were evaluated by CDI. Subgroup analyses were conducted according to whether patients received IOP-lowering drugs treatment and were defined as treated and untreated. Results PSV and EDV were statistically significantly reduced in the OA of POAG eyes (P = 0.0002; P<0.00001; respectively), with significant heterogeneity (Pheterogeneity<0.00001, I2 = 94%; Pheterogeneity<0.00001, I2 = 85%; respectively). Similar results were demonstrated for the CRA (P<0.00001; respectively) and SPCA (P = 0.005; P<0.00001; respectively), with significant heterogeneities for both the CRA (Pheterogeneity<0.00001, I2 = 81%; Pheterogeneity<0.00001, I2 = 98%; respectively) and the SPCA (Pheterogeneity<0.00001, I2 = 96%; Pheterogeneity<0.00001, I2 = 93%; respectively). Significant increases in RI were found in all retrobulbar vessels (P<0.00001; respectively), with significant heterogeneities (Pheterogeneity<0.00001, I2 = 95%; Pheterogeneity<0.00001, I2 = 94%; Pheterogeneity<0.00001, I2 = 97%; respectively). Conclusions This meta-analysis suggests that CDI is a potential diagnostic tool for POAG. PMID:23675419

  8. The Relationship between Central Visual Field Damage and Motor Vehicle Collisions in Primary Open-Angle Glaucoma Patients

    PubMed Central

    Yuki, Kenya; Asaoka, Ryo; Tsubota, Kazuo

    2014-01-01

    Purpose To investigate the relationship between visual field (VF) damage and history of motor vehicle collisions (MVCs) in subjects with primary open-angle glaucoma (POAG). Methods MVC history and driving habits were recorded using patient questionnaires in 247 POAG patients. Patients' driving attitudes (carefulness) were estimated using Rasch analysis. The relationship between MVC outcomes and 52 total deviation (TD) values of integrated binocular VF (IVF), better and worse visual acuities (VAs), age and gender was analyzed using principal component analysis and logistic regression. Results 51 patients had the history of MVCs. Significant difference was observed between patients with and without history of MVCs only for: better VA, a single TD value in the superior-right VF, and the typical distance driven in a week (unpaired t-test, p = 0.002, 0.015 and 0.006, respectively). There was not a significant relationship between MVCs and mean deviation (MD) of IVF (p = 0.41, logistic regression). None of the principal components were significantly correlated with MVC outcome (p>0.05, polynomial logistic regression analysis). There was a significant relationship between IVF MD and Rasch derived Person parameter (R2 = 0.023, p = 0.0095). There was also a significant positive relationship between MVCs and the distance driven in a week (p = 0.005, logistic regression). Conclusions In this study of POAG patients, MVCs were not related to central binocular VF damage. These results suggest the relationship between visual function and driving is not straightforward, and careful consideration should be given when predicting patients' driving ability using their VF. PMID:25545660

  9. [Effectiveness of 3-hydroxypyridine and succinic acid derivatives in complex treatment of primary open-angle glaucoma].

    PubMed

    Volchegorskiĭ, I A; Tur, E V; Soliannikova, O V; Rykun, V S; Sumina, M S; Dmitrienko, V N; Berdnikova, E V

    2012-01-01

    Prospective, placebo-controlled, single-blind, randomized clinical investigation of the influence of domestic 3-hydroxypyridine and succinic acid derivatives (emoxipin, reamberin, mexidol) on the effectiveness of a complex treatment of primary open-angle glaucoma (POAG) has been performed in a group of patients. It is established that intravenous infusion of 3-hydroxypyridine derivatives (emoxipin and mexidol) for two weeks, beginning 14 days after the start of POAG treatment, produced a retinoprotective action, with three months postponed changes in the central retinal artery (CRA) blood velocity. The retinoprotective effect of emoxipin (single dose, 150 mg) was manifested by reduction in the horizontal size of blind spot in two weeks, with the subsequent reduction of the CRA end-diastolic blood velocity observed three months after finish of the infusion therapy. The administration of mexidol (single dose, 300 mg) after 14 days of treatment led to widening of the summarized field of vision (test-object square, 16 mm), accompanied by a decrease in the electrosensitivity threshold of the optic nerve and the intensity of POAG-associated hypothymia. All indices of CRA blood velocity increased three months after termination of mexidol infusions. Reamberin (single dose, 400 ml 1,5% solution of reamberine, containing polyelectrolyte and meglumine succinate mixture) did not show retinoprotective action, but caused proatherogenic changes of blood lipids and 3 months postponed CRA end-diastolic blood velocity increase. The effect of mexidol (which is a derivative of both 3- hydroxypyridine and succinic acid) exceeds that of separate 3-hydroxypyridine (emoxipin) and succinic acid (reamberin) derivatives in the degree of retinoprotection and positive effect on the optic nerve condition and mood of POAG patients.

  10. Optic Disc Perfusion in Primary Open Angle and Normal Tension Glaucoma Eyes Using Optical Coherence Tomography-Based Microangiography

    PubMed Central

    Wen, Joanne C.; Zhang, Qinqin; Xin, Chen; Gupta, Divakar; Mudumbai, Raghu C.; Johnstone, Murray A.; Wang, Ruikang K.; Chen, Philip P.

    2016-01-01

    Purpose To investigate optic disc perfusion differences in normal, primary open-angle glaucoma (POAG), and normal tension glaucoma (NTG) eyes using optical microangiography (OMAG) based optical coherence tomography (OCT) angiography technique. Design Cross-sectional, observational study. Subjects Twenty-eight normal, 30 POAG, and 31 NTG subjects. Methods One eye from each subject was scanned with a 68 kHz Cirrus HD-OCT 5,000-based OMAG prototype system centered at the optic nerve head (ONH) (Carl Zeiss Meditec Inc, Dublin, CA). Microvascular images were generated from the OMAG dataset by detecting the differences in OCT signal between consecutive B-scans. The pre-laminar layer (preLC) was isolated by a semi-automatic segmentation program. Main Outcome Measures Optic disc perfusion, quantified as flux, vessel area density, and normalized flux (flux normalized by the vessel area) within the ONH. Results Glaucomatous eyes had significantly lower optic disc perfusion in preLC in all three perfusion metrics (p<0.0001) compared to normal eyes. The visual field (VF) mean deviation (MD) and pattern standard deviation (PSD) were similar between the POAG and NTG groups, and no differences in optic disc perfusion were observed between POAG and NTG. Univariate analysis revealed significant correlation between optic disc perfusion and VF MD, VF PSD, and rim area in both POAG and NTG groups (p≤0.0288). However, normalized optic disc perfusion was correlated with some structural measures (retinal nerve fiber layer thickness and ONH cup/disc ratio) only in POAG eyes. Conclusions Optic disc perfusion detected with OMAG was significantly reduced in POAG and NTG groups compared to normal controls, but no difference was seen between POAG and NTG groups with similar levels of VF damage. Disc perfusion was significantly correlated with VF MD, VF PSD, and rim area in glaucomatous eyes. Vascular changes at the optic disc as measured using OMAG may provide useful information for

  11. A Common Variant in MIR182 Is Associated With Primary Open-Angle Glaucoma in the NEIGHBORHOOD Consortium

    PubMed Central

    Liu, Yutao; Bailey, Jessica Cooke; Helwa, Inas; Dismuke, W. Michael; Cai, Jingwen; Drewry, Michelle; Brilliant, Murray H.; Budenz, Donald L.; Christen, William G.; Chasman, Daniel I.; Fingert, John H.; Gaasterland, Douglas; Gaasterland, Terry; Gordon, Mae O.; Igo, Robert P.; Kang, Jae H.; Kass, Michael A.; Kraft, Peter; Lee, Richard K.; Lichter, Paul; Moroi, Sayoko E.; Realini, Anthony; Richards, Julia E.; Ritch, Robert; Schuman, Joel S.; Scott, William K.; Singh, Kuldev; Sit, Arthur J.; Song, Yeunjoo E.; Vollrath, Douglas; Weinreb, Robert; Medeiros, Felipe; Wollstein, Gadi; Zack, Donald J.; Zhang, Kang; Pericak-Vance, Margaret A.; Gonzalez, Pedro; Stamer, W. Daniel; Kuchtey, John; Kuchtey, Rachel W.; Allingham, R. Rand; Hauser, Michael A.; Pasquale, Louis R.; Haines, Jonathan L.; Wiggs, Janey L.

    2016-01-01

    Purpose Noncoding microRNAs (miRNAs) have been implicated in the pathogenesis of glaucoma. We aimed to identify common variants in miRNA coding genes (MIR) associated with primary open-angle glaucoma (POAG). Methods Using the NEIGHBORHOOD data set (3853 cases/33,480 controls with European ancestry), we first assessed the relation between 85 variants in 76 MIR genes and overall POAG. Subtype-specific analyses were performed in high-tension glaucoma (HTG) and normal-tension glaucoma subsets. Second, we examined the expression of miR-182, which was associated with POAG, in postmortem human ocular tissues (ciliary body, cornea, retina, and trabecular meshwork [TM]), using miRNA sequencing (miRNA-Seq) and droplet digital PCR (ddPCR). Third, miR-182 expression was also examined in human aqueous humor (AH) by using miRNA-Seq. Fourth, exosomes secreted from primary human TM cells were examined for miR-182 expression by using miRNA-Seq. Fifth, using ddPCR we compared miR-182 expression in AH between five HTG cases and five controls. Results Only rs76481776 in MIR182 gene was associated with POAG after adjustment for multiple comparisons (odds ratio [OR] = 1.23, 95% confidence interval [CI]: 1.11–1.42, P = 0.0002). Subtype analysis indicated that the association was primarily in the HTG subset (OR = 1.26, 95% CI: 1.08–1.47, P = 0.004). The risk allele T has been associated with elevated miR-182 expression in vitro. Data from ddPCR and miRNA-Seq confirmed miR-182 expression in all examined ocular tissues and TM-derived exosomes. Interestingly, miR-182 expression in AH was 2-fold higher in HTG patients than nonglaucoma controls (P = 0.03) without controlling for medication treatment. Conclusions Our integrative study is the first to associate rs76481776 with POAG via elevated miR-182 expression. PMID:27579667

  12. Topical Ocular Sodium 4-Phenylbutyrate Rescues Glaucoma in a Myocilin Mouse Model of Primary Open-Angle Glaucoma

    PubMed Central

    Zode, Gulab S.; Bugge, Kevin E.; Mohan, Kabhilan; Grozdanic, Sinisa D.; Peters, Joseph C.; Koehn, Demelza R.; Anderson, Michael G.; Kardon, Randy H.; Stone, Edwin M.

    2012-01-01

    Purpose. Mutations in the myocilin gene (MYOC) are the most common known genetic cause of primary open-angle glaucoma (POAG). The purpose of this study was to determine whether topical ocular sodium 4-phenylbutyrate (PBA) treatment rescues glaucoma phenotypes in a mouse model of myocilin-associated glaucoma (Tg-MYOCY437H mice). Methods. Tg-MYOCY437H mice were treated with PBA eye drops (n = 10) or sterile PBS (n = 8) twice daily for 5 months. Long-term safety and effectiveness of topical PBA (0.2%) on glaucoma phenotypes were examined by measuring intraocular pressure (IOP) and pattern ERG (PERG), performing slit lamp evaluation of the anterior chamber, analyzing histologic sections of the anterior segment, and comparing myocilin levels in the aqueous humor and trabecular meshwork of Tg-MYOCY437H mice. Results. Tg-MYOCY437H mice developed elevated IOP at 3 months of age when compared with wild-type (WT) littermates (n = 24; P < 0.0001). Topical PBA did not alter IOP in WT mice. However, it significantly reduced elevated IOP in Tg-MYOCY437H mice to the level of WT mice. Topical PBA-treated Tg-MYOCY437H mice also preserved PERG amplitudes compared with vehicle-treated Tg-MYOCY437H mice. No structural abnormalities were observed in the anterior chamber of PBA-treated WT and Tg-MYOCY437H mice. Analysis of the myocilin in the aqueous humor and TM revealed that PBA significantly improved the secretion of myocilin and reduced myocilin accumulation as well as endoplasmic reticulum (ER) stress in the TM of Tg-MYOCY437H mice. Furthermore, topical PBA reduced IOP elevated by induction of ER stress via tunicamycin injections in WT mice. Conclusions. Topical ocular PBA reduces glaucomatous phenotypes in Tg-MYOCY437H mice, most likely by reducing myocilin accumulation and ER stress in the TM. Topical ocular PBA could become a novel treatment for POAG patients with myocilin mutations. PMID:22328638

  13. Risk Factors for Motor Vehicle Collisions in Patients with Primary Open-Angle Glaucoma: A Multicenter Prospective Cohort Study

    PubMed Central

    Yuki, Kenya; Awano-Tanabe, Sachiko; Ono, Takeshi; Shiba, Daisuke; Murata, Hiroshi; Asaoka, Ryo; Tsubota, Kazuo

    2016-01-01

    Purpose To identify the incidence rate of motor vehicle collisions (MVCs) in patients with no ocular pathology other than primary open-angle glaucoma (POAG) and determine the putative risk factors for MVCs in this group of patients. Methods We designed a prospective cohort study across three centers utilizing a consecutive sampling method to identify all patients with POAG between the ages of 40 and 80 years old. Patients with glaucoma were consecutively screened for eligibility. All study participants answered a questionnaire about motor vehicle collisions at baseline, and answered the questionnaire again every 12 months (± 1 month) after baseline for three years. A binocular integrated visual field was calculated for each patient by merging a patient’s monocular Humphrey Field Analyzer (HFA) visual fields (VFs), using the ‘best sensitivity’ method. Patients with incident MVCs were defined as the “MVC+” group and patients without incident MVCs were defined as the “MVC-" group. Adjusted odds ratios for the incidence of MVCs were estimated with a logistic regression model. Results One hundred and ninety-one Japanese POAG patients were analyzed in this study. The age of the participants was 63.7 ± 10.2 [mean ± standard deviation]. A total of 28 participants experienced a MVC during the follow up period of three years (4.9% per year). Ten patients (5.2%) experienced a MVC in the first year, 13 patients (6.8%) in the second year, and 11 patients (5.8%) in the third year (some patients experienced multiple MVCs over different years). Best corrected visual acuity in the worst eye was significantly worse in the MVC+ group (0.03 ± 0.01, mean ± standard deviation, LogMar) compared with the MVC- group (0.01 ± 0.003, p = 0.01), and was the only variable identified as a significant predictor of future MVCs in the multiple logistic regression model [odds ratio: 1.2, 95% confidence interval (CI): 1.1 to 1.4]. Conclusion Deterioration in visual acuity in the

  14. Association between primary open angle glaucoma and genetic polymorphisms GSTM1/GSTT1 in patients from Goiânia Central-West Region of Brazil.

    PubMed

    Silva, C T X; Costa, N B; Silva, K S F; Silva, R E; Moura, K K V O

    2014-10-31

    In this study, we evaluated the genotype profile of GSTM1 and GSTT1 polymorphisms in patient carriers of primary open-angle glaucoma in the population of Goiânia, GO, Brazil. This case-control study included 100 Brazilian patients with glaucoma and 53 patients without glaucoma. Blood samples were genotyped for polymorphisms in GST genes using polymerase chain reaction-based methods. Polymorphism frequencies were compared using the X(2) test and odds ratio (α = 0.05). The GSTM1-present genotype was 40% in the glaucoma group and 71.6% in the control group, while the GSTM1 null genotype was 60 and 28.3% in the same groups, respectively. The GSTT1-present genotype was 52% in the primary open-angle glaucoma group and 66% in the control group; the null genotype was 48% in the case group and 34% in the control group. The GSTM1 null genotype was more frequent in the glaucoma group than in the control group (P = 0.0004; odds ratio = 6.7; 95% confidence interval = 2.7- 20.3). The combined GSTM1 null and GSTT1-present genotypes were more frequent in the primary open-angle glaucoma group compared to the control group (P = 0.02; odds ratio = 3.1; 95% confidence interval = 1.2-7.9).

  15. Novel and known MYOC exon 3 mutations in an admixed Peruvian primary open-angle glaucoma population

    PubMed Central

    Mendoza-Reinoso, Veronica; Guevara-Fujita, Maria L.; Fernández, Silvia; Vargas, Enrique; Castillo-Herrera, Wilder; Perez-Grossmann, Rodolfo; Lizaraso-Caparó, Frank; Richards, Julia E.; Fujita, Ricardo

    2012-01-01

    Purpose The aim of this study was to characterize a representative sample of the Peruvian population suffering open-angle glaucoma (OAG) with respect to the myocilin gene (MYOC) mutations, glaucoma phenotype, and ancestry for future glaucoma risk assessment. Methods DNA samples from 414 unrelated Peruvian subjects, including 205 open-angle glaucoma cases (10 juvenile glaucoma [JOAG], 19 normal-tension glaucoma [NTG], and 176 POAG) and 209 randomly sampled controls, were screened for nucleotide changes in MYOC exon 3 by conformational sensitive gel electrophoresis (CSGE) and mutation screening. Results We identified a probable causative novel MYOC missense mutation, Gly326Ser, in one POAG case and found a consistent genotype-phenotype correlation in eight of his relatives. We also found the known causative MYOC mutation Trp286Arg in one JOAG case and one POAG case. A known causative single base MYOC deletion, T1357, was found in one POAG case. Two previously reported silent polymorphisms, Thr325Thr and Tyr347Tyr, were found in both the case and the control populations. A novel missense variant, Met476Arg, was identified in two unrelated controls. Conclusions The screening of exon 3 of MYOC in a representative sample of 205 independent POAG patients from Peru and 209 matched controls identified novel and previously reported mutations (both pathogenic and nonpathogenic) from other global regions. These results reflect the complex admixture of Amerindian and Old World ancestry in urban populations of Latin America, in general, and in Peru, in particular. It will be important to gather information about the ancestral origin of MYOC and other POAG gene mutations to develop screening panels and risk assessment for POAG in Peru. PMID:22879734

  16. Common variants near CAV1 and CAV2 are associated with primary open-angle glaucoma in Caucasians from the USA.

    PubMed

    Wiggs, Janey L; Kang, Jae Hee; Yaspan, Brian L; Mirel, Daniel B; Laurie, Cathy; Crenshaw, Andrew; Brodeur, Wendy; Gogarten, Stephanie; Olson, Lana M; Abdrabou, Wael; DelBono, Elizabeth; Loomis, Stephanie; Haines, Jonathan L; Pasquale, Louis R

    2011-12-01

    Primary open-angle glaucoma (POAG) is a genetically complex common disease characterized by progressive optic nerve degeneration that results in irreversible blindness. Recently, a genome-wide association study (GWAS) for POAG in an Icelandic population identified significant associations with single nucleotide polymorphisms (SNPs) between the CAV1 and CAV2 genes on chromosome 7q31. In this study, we confirm that the identified SNPs are associated with POAG in our Caucasian US population and that specific haplotypes located in the CAV1/CAV2 intergenic region are associated with the disease. We also present data suggesting that associations with several CAV1/CAV2 SNPs are significant mostly in women.

  17. Comparison of self-measured diurnal intraocular pressure profiles using rebound tonometry between primary angle closure glaucoma and primary open angle glaucoma patients

    PubMed Central

    Tan, Shaoying; Baig, Nafees; Hansapinyo, Linda; Jhanji, Vishal; Wei, Shihui; Tham, Clement C.

    2017-01-01

    Purpose To document the diurnal intraocular pressure (IOP) profile with rebound tonometry performed by primary glaucoma patients in non-clinic environment. Patients and methods Fifty-three medically-treated eyes of 31 primary angle closure glaucoma (PACG) and 22 primary open angle glaucoma (POAG) patients with no previous eye surgery were recruited. Diurnal IOP was measured 5 times per day at four-hourly intervals from 08:00 to 24:00 for 1 week in patients’ study eye using rebound tonometry in a non-clinic environment. The diurnal IOP profiles were compared between PACG and POAG eyes. Results For both PACG and POAG eyes, mean patient-measured IOP was highest in the morning, gradually decreased over the course of a day, and was lowest by midnight (p < 0.001). The diurnal IOP fluctuation ± 1 standard deviation (SD), as documented by SD in daily IOP values, was lower in PACG group (1.6 ± 1.1 mmHg) than in POAG group (2.0 ± 1.2 mmHg; p = 0.049). The mean trough IOP ± 1 SD was higher in PACG group (12.9 ± 2.8 mmHg), compared to POAG group (11.5 ± 3.8 mmHg; p = 0.041). The mean IOP level at midnight ± 1 SD in PACG group (14.0 ± 3.2 mmHg) was higher than that in POAG group (12.1 ± 3.7 mmHg; p = 0.013). Conclusions IOP in primary glaucoma patients was highest in the morning, and decreased over the course of a day in non-clinic environment. Treated diurnal IOP fluctuation seemed to be greater in POAG than PACG eyes. PMID:28333942

  18. Examining Delay Intervals in the Diagnosis and Treatment of Primary Open Angle Glaucoma in an Egyptian Population and Its Impact on Lifestyle

    PubMed Central

    Abu Hussein, Nahla B.; Habib, Ahmed E.; El Sayed, Yasmine M.

    2016-01-01

    Purpose. To examine causes as well as extent of delay in diagnosis and treatment of primary open angle glaucoma patients in a sample of Egyptians. Patients and Methods. 440 patients with primary open angle glaucoma were interviewed to evaluate delay in their diagnosis and treatment. The extent and cause of delay were investigated. The total delay interval, if any, was correlated with socioeconomic and other factors. Results. The median total delay was one year, with 50% of patients having a total delay of 1 year or less, of which 25% exhibited zero total delay. 25% of patients had a delay ranging from 1 to 3 years, and 25% had a total delay ranging from 3 to 27 years. Diagnostic delay accounted for 43.03% of cases. Longer delays were met in patients with certain socioeconomic factors. Patients with a positive family history of glaucoma displayed shorter delay periods. Conclusion. Significant delay in the diagnosis and treatment of glaucoma was found. Poor socioeconomic status seems to hinder timely diagnosis and treatment of POAG. Certain socioeconomic factors seem to correlate with the extent of delay. More effort is thus needed to subsidize the cost of investigations and treatment for glaucoma patients. PMID:28116140

  19. Distribution of COL8A2 and COL8A1 gene variants in Caucasian primary open angle glaucoma patients with thin central corneal thickness

    PubMed Central

    Desronvil, T.; Logan-Wyatt, D.; Abdrabou, W.; Triana, M.; Jones, R.; Taheri, S.; Del Bono, E.; Pasquale, L.R.; Olivier, M.; Haines, J.L.; Fan, B.J.

    2010-01-01

    Purpose One approach to identify genes that contribute to common complex ocular disorders such as primary open angle glaucoma (POAG) is to study the genetic determinates of endophenotypes that are defined by underlying pre-disposing heritable quantitative traits such as central corneal thickness (CCT). Collagen VIII is a major component of Descemet’s membrane and studies in mice have indicated that targeted inactivation of the genes encoding the collagen type 8 alpha1 (Col8a1) and collagen type 8 alpha2 (Col8a2) subunits (COL8A1 and COL8A2) results in thinning of the corneal stroma and of Descemet’s membrane. The purpose of this study is to evaluate COL8A1 and COL8A2 as candidate genes for thin CCT in human POAG patients. Methods 100 Caucasian POAG patients were enrolled in this study. The entire COL8A1 and COL8A2 coding sequence was determined in 8 patients with CCT<513 µm (one standard deviation (36 microns) below the mean (550 microns) and 8 patients with CCT>586 µm (one standard deviation above the mean). Selected COL8A2 exons containing variants of interest were sequenced in the full POAG cohort. Association and quantitative trait analyses were performed. Results Three patients with CCT less than 513 µm and advanced POAG were found to have missense changes in COL8A2; two patients had a previously identified mutation, R155Q and one had a novel change, P678L (p=0.0035, Fisher’s exact test). Missense changes were not found in any of the patients with CCT>513 µm and missense changes in the COL8A1 gene were not found in any patient. One common COL8A2 SNP, rs274754 was also statistically associated with CCT (p=0.018). Conclusions In this study we have identified COL8A2 missense changes in a group of Caucasian patients with very thin CCT and advanced POAG. These results suggest that DNA sequence variants in the COL8A2 gene may be associated with thin corneas in some glaucoma patients. Further study of COL8A2 variants in other patient populations, especially

  20. Patient-Reported Vision-Related Quality-of-Life Differences between Primary Angle-Closure Glaucoma and Primary Open-Angle Glaucoma

    PubMed Central

    Guo, Chao-Yu; Chen, Yu-Jing; Chen, Mei-Ju; Ko, Yu-Chieh; Huang, Nicole; Liu, Catherine Jui-ling

    2016-01-01

    Purpose To investigate the different impacts on patient-reported vision-related quality of life (pVRQOL) outcomes in patients with primary angle-closure glaucoma(PACG) and primary open-angle glaucoma(POAG). Methods Prospective cross-sectional study. PACG and POAG patients who had a best-corrected visual acuity(BCVA) in the better eye equal to or better than 20/60, intraocular pressure controlled at or below 25 mmHg and reliable visual field test were invited to participate. The control group included patients with BCVA in the better eye equal to or better than 20/60 and who did not have major eye disease. A validated Taiwanese version of the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25(T)) was performed to assess pVRQOL. The association between each domain of NEI VFQ-25(T) among 3 groups was determined using multivariable linear regression analysis. Results A total of 106 PACG, 186 POAG, and 95 controls were enrolled. In multivariable regression analysis of all three groups(PACG/POAG/controls), compared to POAG, PACG showed a weakly positive association with social functioning (R2 = 0.13, β = 0.22, P = 0.04). PACG showed no significantly negative impact on pVRQOL compared to controls. Taking only glaucoma patients into consideration, PACG patients had a higher score on social functioning compared to POAG (R2 = 0.16, β = 0.27, P = 0.01). The results of other domains of NEI VFQ-25(T) between the two groups did not differ significantly(p>0.05). Conclusions In patients with controlled disease, the impact of PACG and POAG on most domains of NEI VFQ-25(T) were similar, except for better social functioning in PACG compared to POAG. PMID:27690232

  1. Common variants near CAV1 and CAV2 are associated with primary open-angle glaucoma in Caucasians from the USA

    PubMed Central

    Wiggs, Janey L.; Hee Kang, Jae; Yaspan, Brian L.; Mirel, Daniel B.; Laurie, Cathy; Crenshaw, Andrew; Brodeur, Wendy; Gogarten, Stephanie; Olson, Lana M.; Abdrabou, Wael; DelBono, Elizabeth; Loomis, Stephanie; Haines, Jonathan L.; Pasquale, Louis R.

    2011-01-01

    Primary open-angle glaucoma (POAG) is a genetically complex common disease characterized by progressive optic nerve degeneration that results in irreversible blindness. Recently, a genome-wide association study (GWAS) for POAG in an Icelandic population identified significant associations with single nucleotide polymorphisms (SNPs) between the CAV1 and CAV2 genes on chromosome 7q31. In this study, we confirm that the identified SNPs are associated with POAG in our Caucasian US population and that specific haplotypes located in the CAV1/CAV2 intergenic region are associated with the disease. We also present data suggesting that associations with several CAV1/CAV2 SNPs are significant mostly in women. PMID:21873608

  2. Genetic heterogeneity of primary open angle glaucoma and ocular hypertension: linkage to GLC1A associated with an increased risk of severe glaucomatous optic neuropathy.

    PubMed Central

    Brézin, A P; Béchetoille, A; Hamard, P; Valtot, F; Berkani, M; Belmouden, A; Adam, M F; Dupont de Dinechin, S; Bach, J F; Garchon, H J

    1997-01-01

    The GLC1A locus for autosomal dominant juvenile and middle age onset primary open angle glaucoma (OAG) has been mapped to chromosome 1q21-q31. OAG, however, is a heterogeneous disease. We tested linkage of OAG and ocular hypertension (OHT), a major risk factor for OAG, to GLC1A in eight French families with multiple cases of juvenile and middle age onset OAG. There was strong evidence of genetic heterogeneity, four families being linked to GLC1A and two or three others being unlinked, depending on whether the complete OAG phenotype was analysed alone or jointly with OHT. Peak intraocular pressure (IOP) did not differ significantly between the two groups of families, while linkage to GLC1A conferred a highly increased risk of developing OAG and of having severe glaucomatous optic neuropathy. Testing linkage of familial OAG to GLC1A may therefore have prognostic value too. PMID:9222961

  3. Determination of Serum Ceruloplasmin Concentration in Patients with Primary Open Angle Glaucoma with Cataract and Patients with Cataract Only: A Pilot Study

    PubMed Central

    Sarnat-Kucharczyk, Monika; Rokicki, Wojciech; Zalejska-Fiolka, Jolanta; Pojda-Wilczek, Dorota; Mrukwa-Kominek, Ewa

    2016-01-01

    Background The aim of this article was to describe the role of ceruloplasmin and to report preliminary results of ceruloplasmin concentrations in patients with primary open-angle glaucoma (POAG) with cataract and in patients with only cataract. Glaucoma, a neurodegenerative disease, is a heterogeneous group of conditions characterized by loss of retinal ganglion cells (RGC), their axons, progressive optic nerve damage, and visual field deterioration. Material/Methods The POAG group included 30 patients and the cataract group included 25 patients. Results Ceruloplasmin plays an essential role in iron metabolism and inactivating free radicals. In the presented pilot study, serum ceruloplasmin level was lower in the POAG group in comparison to the group with only cataract. Conclusions In treating persistent inflammation in the course of glaucoma, antiglaucoma drugs may increase the permeability of the blood-ocular barrier, which may be connected with the lower concentration of serum ceruloplasmin in the glaucoma patients group. PMID:27109647

  4. [Genetic variants of CYP1B1 and WDR36 in the patients with primary congenital glaucoma and primary open angle glaucoma from Saint-Petersburg].

    PubMed

    Motushchuk, A E; Komarova, T Iu; Grudinina, N A; Rakhmanov, V V; Mandel'shtam, M Iu; Astakhov, Iu S; Vasil'ev, V B

    2009-12-01

    In 32 patients with primary congenital glaucoma (PCG), a search for mutations in the myocilin (MYOC), cytochrome P450B1 (CYP1B1), and WDR36 genes was performed. The Q368X mutation in myocilin gene, typical of the patients with adult-onset primary open-angle glaucoma (POAG), was not detected in the PCG patients. Screening of the CYP1B1 introns 2 and 3 for the presence of mutations in PCG patients revealed only six DNA polymorphisms, including IVS1-12ntT>C (g.3793 T>C), A119S (g.4160 G>T; GCC>TCC), G188G (g.4369 C>A; GGC>GGA), L432V (G.8131 C>G; CTG>GTG), D449D (g.8184 C>T; GAC>GAT), and N453S (g.8195 A>G; AAC>AGC) (nucleotide numbering is given in accordance with the GenBank sequence U56438). In the groups of PCG patients and donors without eye diseases, the frequencies of these variants were not statistically significantly different, pointing to the neutrality of these polymorphisms. Furthermore, the CYP1B1 polymorphism L432V, considered to be associated with POAG in some world populations, was not associated with this disease in the patients from St. Petersburg. DNA collections obtained from the POAG and PCG patients and from the control group were tested for the carriage of the worldwide distributed mutations of the WRD36 gene, D658G, R529Q, A449T, and N355S. D658G variant was found with equally low frequencies in the groups of POAG and PCG patients, as well as in the control group. Mutations A449T and R529Q were found only once each, while mutation N355S was not detected in any of the groups examined. Our results indicate that the WDR36 variants make no substantial contribution to the development of POAG and PCG in the patients from St. Petersburg and represent normal DNA polymorphism. It is likely that in most of the PCG patients from the population examined the disease is not associated with the CYP1B1 gene defects.

  5. Localization of a locus (GLC1B) for adult-onset primary open angle glaucoma to the 2cen-q13 region

    SciTech Connect

    Stoilova, D.; Trifan, O.C.; Sarfarazi, M.

    1996-08-15

    Primary open angle glaucoma (GLC1) is a common ocular disorder with a characteristic degeneration of the optic nerve and visual field defects that is often associated with an elevated intraocular pressure. The severe but rare juvenile-onset type has previously been mapped to 1q21-q31, and its genetic heterogeneity has been established. Herein, we present a new locus (GLC1B) for one form of GLC1 on chromosome 2cen-q13 with a clinical presentation of low to moderate intraocular pressure, onset in late 40s, and a good response to medical treatment. Two-point and haplotype analyses of affected and unaffected meioses in six families provided maximum linkage information with D2S417, GATA112EO3, D2S113, D2S373, and D2S274 (lod scores ranging from 3.11 to 6.48) within a region of 8.5 cM that is flanked by D2S2161 and D2S2264. Analysis of affected meioses alone revealed no recombination with an additional two markers (D2S2264 and D2S135) in a region of 11.2 cM that is flanked by D2S2161 and D2S176. Analysis of unaffected meioses identified only one healthy 86-year-old male who has inherited the entire affected haplotype and, hence, is a gene carrier for this condition. Eight additional families with similar and/or different clinical presentation did not show any linkage to this region and, therefore, provided evidence for genetic heterogeneity of adult-onset primary open angle glaucoma. 63 refs., 2 figs., 2 tabs.

  6. Identification of Mutations in Myocilin and Beta-1,4-galactosyltransferase 3 Genes in a Chinese Family with Primary Open-angle Glaucoma

    PubMed Central

    Liao, Rong-Feng; Zhong, Zi-Lin; Ye, Min-Jie; Han, Li-Yun; Ye, Dong-Qing; Chen, Jian-Jun

    2016-01-01

    Background: Glaucoma is a major cause of irreversible blindness worldwide. There is evidence showing that a subset of the disease is genetically determined. In this study, we screened for mutations in chromosome 1q-linked open-angle glaucoma (GLC1A) in a Chinese family with primary open-angle glaucoma (POAG). Methods: A total of 23 members from five generations of a family were enrolled and underwent thorough ophthalmologic examinations. In addition, 200 unrelated healthy Chinese controls were also recruited as normal control. GLC1A gene was amplified by polymerase chain reaction, and DNA sequencing was performed to screen for mutations. Results: Six members were diagnosed as POAG, with severe clinical manifestations, and history of high intraocular pressures. The mean age of disease onset was 26.3 years. However, the others were asymptomatic. In six affected and three asymptomatic members, gene sequencing revealed a mutation c.C1456T in exon 3 of myocilin gene (MYOC). Furthermore, we also identified a novel mutation c.G322A in beta-1,4-galactosyltransferase 3 (B4GALT3) gene in all six affected and three asymptomatic members, which was not reported previously in POAG patients. The two newly identified variants were absent in other family members as well as controls. Conclusion: The mutations c.1456C

  7. Controlled five-year follow-up study of laser trabeculoplasty as primary therapy for open-angle glaucoma

    SciTech Connect

    Tuulonen, A.; Niva, A.K.; Alanko, H.I.

    1987-10-15

    We followed up 32 eyes of 32 patients with early glaucoma (22 with capsular glaucoma and ten with simple glaucoma) who received laser trabeculoplasty as a primary therapy. These eyes were compared with a matched control group of 32 eyes treated with medication initially. The success rate (intraocular pressure below 22 mm Hg with laser alone or medication alone) at five years was 50% (16 of 32 eyes) in the laser-treated group and 22% (seven of 32 eyes) in the control group (P less than .02). The control group required more modifications of their therapy to control intraocular pressure. The neuroretinal rim area in the control eyes decreased 2.5 times as much as in the laser group (P = .017). Changes in the Friedmann visual fields did not differ significantly between the two groups.

  8. Whole exome sequencing implicates eye development, the unfolded protein response and plasma membrane homeostasis in primary open-angle glaucoma

    PubMed Central

    Souzeau, Emmanuelle; Sharma, Shiwani; Landers, John; Mills, Richard; Goldberg, Ivan; Healey, Paul R.; Graham, Stuart; Hewitt, Alex W.; Mackey, David A.; Galanopoulos, Anna; Casson, Robert J.; Ruddle, Jonathan B.; Ellis, Jonathan; Leo, Paul; Brown, Matthew A.; MacGregor, Stuart; Lynn, David J.; Burdon, Kathryn P.; Craig, Jamie E.

    2017-01-01

    Purpose To identify biological processes associated with POAG and its subtypes, high-tension (HTG) and normal-tension glaucoma (NTG), by analyzing rare potentially damaging genetic variants. Methods A total of 122 and 65 unrelated HTG and NTG participants, respectively, with early onset advanced POAG, 103 non-glaucoma controls and 993 unscreened ethnicity-matched controls were included in this study. Study participants without myocilin disease-causing variants and non-glaucoma controls were subjected to whole exome sequencing on an Illumina HiSeq2000. Exomes of participants were sequenced on an Illumina HiSeq2000. Qualifying variants were rare in the general population (MAF < 0.001) and potentially functionally damaging (nonsense, frameshift, splice or predicted pathogenic using SIFT or Polyphen2 software). Genes showing enrichment of qualifying variants in cases were selected for pathway and network analysis using InnateDB. Results POAG cases showed enrichment of rare variants in camera-type eye development genes (p = 1.40×10–7, corrected p = 3.28×10–4). Implicated eye development genes were related to neuronal or retinal development. HTG cases were significantly enriched for key regulators in the unfolded protein response (UPR) (p = 7.72×10–5, corrected p = 0.013). The UPR is known to be involved in myocilin-related glaucoma; our results suggest the UPR has a role in non-myocilin causes of HTG. NTG cases showed enrichment in ion channel transport processes (p = 1.05×10–4, corrected p = 0.027) including calcium, chloride and phospholipid transporters involved in plasma membrane homeostasis. Network analysis also revealed enrichment of the MHC Class I antigen presentation pathway in HTG, and the EGFR1 and cell-cycle pathways in both HTG and NTG. Conclusion This study suggests that mutations in eye development genes are enriched in POAG. HTG can result from aberrant responses to protein misfolding which may be amenable to molecular chaperone therapy. NTG

  9. Preservative-free bimatoprost 0.03% in patients with primary open-angle glaucoma or ocular hypertension in clinical practice

    PubMed Central

    Pillunat, Lutz E; Eschstruth, Peter; Häsemeyer, Stefan; Thelen, Ulrich; Foja, Christian; Leaback, Richard; Pfennigsdorf, Stefan

    2016-01-01

    Background Intraocular pressure (IOP)-lowering medications for primary open-angle glaucoma and ocular hypertension commonly contain preservatives that can cause ocular surface damage in many patients. The purpose of this study was to evaluate the efficacy and tolerability of, and compliance to, preservative-free (PF) bimatoprost 0.03% in patients with primary open-angle glaucoma or ocular hypertension (IOP ≥18 mmHg) in a clinical practice setting. Methods This open-label study observed patients who were switched to PF bimatoprost 0.03% for medical reasons. IOP was measured at baseline and ~12 weeks later at the final visit, and the change in IOP was calculated. Tolerability and continuation of therapy were assessed at two follow-up visits. Results A total of 1,830 patients were included in the study, and complete IOP data were available for 1,543 patients. Mean IOP was reduced by 23% from 21.64 mmHg to 16.59 mmHg (P<0.0001). In subgroup analyses, the mean IOP was significantly reduced compared with baseline, regardless of prior therapy, including those previously treated with PF monotherapy. A total of 85.7% of physicians reported the IOP-lowering efficacy of PF bimatoprost 0.03% to be as expected or better than expected. Adverse events (AEs) were experienced by 5.7% of patients, and there were no serious AEs reported. The most common AEs were eye irritation (1.7%) and hyperemia (1.4%). Physician-reported treatment compliance was reported as better than (48.7%) or equal to (43.6%) prior treatment in most patients. Most patients (82%) were expected to continue PF bimatoprost 0.03% after the end of the study. Conclusion This observational study showed that, in clinical practice, switching to PF bimatoprost 0.03% was associated with a significant IOP reduction from baseline. There was a low AE rate. PF bimatoprost 0.03% may, therefore, be an effective treatment option for patients who are intolerant of preservatives or have an inadequate response to prior IOP

  10. Localization of the fourth locus (GLC1E) for adult-onset primary open-angle glaucoma to the 10p15-p14 region.

    PubMed Central

    Sarfarazi, M; Child, A; Stoilova, D; Brice, G; Desai, T; Trifan, O C; Poinoosawmy, D; Crick, R P

    1998-01-01

    One of the major causes of blindness is primary open-angle glaucoma, which affects millions of elderly people worldwide. Genetic studies have so far mapped three loci for the adult-onset form of this condition to the 2cen-q13, 3q21-q24, and 8q23 regions. Herein, we report the localization of a fourth locus, to the 10p15-p14 region, in one large British family with a classical form of normal-tension open-angle glaucoma. Of the 42 meioses genotyped in this pedigree, 39 subjects (16 affected) inherited a haplotype compatible with their prior clinical designation, whereas the remaining 3 were classified as unknown. Although a maximum LOD score of 10.00 at a recombination fraction of straight theta=.00 was obtained with D10S1216, 21 other markers provided significant values, varying between 3.77 and 9.70. When only the affected meioses of this kindred were analyzed, LOD scores remained statistically significant, ranging from 3.16 (D10S527) to 3.57 (D10S506). Two critical recombinational events in the affected subjects positioned this new locus to a region of approximately 21 cM, flanked by D10S1729 and D10S1664. However, an additional recombination in a 59-year-old unaffected female suggests that this locus resides between D10S585 (or D10S1172) and D10S1664, within a genetic distance of 5-11 cM. However, the latter minimum region must be taken cautiously, because the incomplete penetrance has previously been documented for this group of eye conditions. A partial list of genes that positionally are considered as candidates includes NET1, PRKCT, ITIH2, IL2RA, IL15RA, IT1H2, hGATA3, the mRNA for open reading frame KIAA0019, and the gene for D123 protein. PMID:9497264

  11. Structural and functional brain changes in early- and mid-stage primary open-angle glaucoma using voxel-based morphometry and functional magnetic resonance imaging.

    PubMed

    Jiang, Ming-Ming; Zhou, Qing; Liu, Xiao-Yong; Shi, Chang-Zheng; Chen, Jian; Huang, Xiang-He

    2017-03-01

    To investigate structural and functional brain changes in patients with primary open-angle glaucoma (POAG) by using voxel-based morphometry based on diffeomorphic anatomical registration through exponentiated Lie algebra (VBM-DARTEL) and blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI), respectively.Thirteen patients diagnosed with POAG and 13 age- and sex-matched healthy controls were enrolled in the study. For each participant, high-resolution structural brain imaging and blood flow imaging were acquired on a 3.0-Tesla magnetic resonance imaging (MRI) scanner. Structural and functional changes between the POAG and control groups were analyzed. An analysis was carried out to identify correlations between structural and functional changes acquired in the previous analysis and the retinal nerve fiber layer (RNFL).Patients in the POAG group showed a significant (P < 0.001) volume increase in the midbrain, left brainstem, frontal gyrus, cerebellar vermis, left inferior parietal lobule, caudate nucleus, thalamus, precuneus, and Brodmann areas 7, 18, and 46. Moreover, significant (P < 0.001) BOLD signal changes were observed in the right supramarginal gyrus, frontal gyrus, superior frontal gyrus, left inferior parietal lobule, left cuneus, and left midcingulate area; many of these regions had high correlations with the RNFL.Patients with POAG undergo widespread and complex changes in cortical brain structure and blood flow. (ClinicalTrials.gov number: NCT02570867).

  12. Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open angle glaucoma

    PubMed Central

    Cooke Bailey, Jessica N.; Loomis, Stephanie J.; Kang, Jae H.; Allingham, R. Rand; Gharahkhani, Puya; Khor, Chiea Chuen; Burdon, Kathryn P.; Aschard, Hugues; Chasman, Daniel I.; Igo, Robert P.; Hysi, Pirro G.; Glastonbury, Craig A.; Ashley-Koch, Allison; Brilliant, Murray; Brown, Andrew A.; Budenz, Donald L.; Buil, Alfonso; Cheng, Ching-Yu; Choi, Hyon; Christen, William G.; Curhan, Gary; De Vivo, Immaculata; Fingert, John H.; Foster, Paul J.; Fuchs, Charles; Gaasterland, Douglas; Gaasterland, Terry; Hewitt, Alex W.; Hu, Frank; Hunter, David J.; Khawaja, Anthony P.; Lee, Richard K.; Li, Zheng; Lichter, Paul R.; Mackey, David A.; McGuffin, Peter; Mitchell, Paul; Moroi, Sayoko E.; Perera, Shamira A.; Pepper, Keating W.; Qi, Qibin; Realini, Tony; Richards, Julia E.; Ridker, Paul M; Rimm, Eric; Ritch, Robert; Ritchie, Marylyn; Schuman, Joel S.; Scott, William K.; Singh, Kuldev; Sit, Arthur J.; Song, Yeunjoo E.; Tamimi, Rulla M.; Topouzis, Fotis; Viswanathan, Ananth C.; Verma, Shefali Setia; Vollrath, Douglas; Wang, Jie Jin; Weisschuh, Nicole; Wissinger, Bernd; Wollstein, Gadi; Wong, Tien Y.; Yaspan, Brian L.; Zack, Donald J.; Zhang, Kang; Weinreb, Robert N.; Pericak-Vance, Margaret A.; Small, Kerrin; Hammond, Christopher J.; Aung, Tin; Liu, Yutao; Vithana, Eranga N.; MacGregor, Stuart; Craig, Jamie E.; Kraft, Peter; Howell, Gareth; Hauser, Michael A.; Pasquale, Louis R.; Haines, Jonathan L.; Wiggs, Janey L.

    2015-01-01

    Primary open angle glaucoma (POAG) is a leading cause of blindness world-wide. To identify new susceptibility loci, we meta-analyzed GWAS results from 8 independent studies from the United States (3,853 cases and 33,480 controls) and investigated the most significant SNPs in two Australian studies (1,252 cases and 2,592 controls), 3 European studies (875 cases and 4,107 controls) and a Singaporean Chinese study (1,037 cases and 2,543 controls). A meta-analysis of top SNPs identified three novel loci: rs35934224[T] within TXNRD2 (odds ratio (OR) = 0.78, P = 4.05×10−11 encoding a mitochondrial protein required for redox homeostasis; rs7137828[T] within ATXN2 (OR = 1.17, P = 8.73×10−10), and rs2745572[A] upstream of FOXC1 (OR = 1.17, P = 1.76×10−10). Using RT-PCR and immunohistochemistry, we show TXNRD2 and ATXN2 expression in retinal ganglion cells and the optic nerve head. These results identify new pathways underlying POAG susceptibility and suggest novel targets for preventative therapies. PMID:26752265

  13. Sensory stimulation for lowering intraocular pressure, improving blood flow to the optic nerve and neuroprotection in primary open-angle glaucoma.

    PubMed

    Rom, Edith

    2013-12-01

    Primary open-angle glaucoma is a group of optic neuropathies that can lead to irreversible blindness. Sensory stimulation in the form of acupuncture or ear acupressure may contribute to protecting patients from blindness when used as a complementary method to orthodox treatment in the form of drops, laser or surgery. The objective of this article is to provide a narrative overview of the available literature up to July 2012. It summarises reported evidence on the potential beneficial effects of sensory stimulation for glaucoma. Sensory stimulation appears to significantly enhance the pressure-lowering effect of orthodox treatments. Studies suggest that it may also improve blood flow to the eye and optic nerve head. Furthermore, it may play a role in neuroprotection through regulating nerve growth factor and brain-derived neurotrophic factor and their receptors, thereby encouraging the survival pathway in contrast to the pathway to apoptosis. Blood flow and neuroprotection are areas that are not directly influenced by orthodox treatment modalities. Numerous different treatment protocols were used to investigate the effect of sensory stimulation on intraocular pressure, blood flow or neuroprotection of the retina and optic nerve in the animal model and human pilot studies. Objective outcomes were reported to have been evaluated with Goldmann tonometry, Doppler ultrasound techniques and electrophysiology (pattern electroretinography, visually evoked potentials), and supported with histological studies in the animal model. Taken together, reported evidence from these studies strongly suggests that sensory stimulation is worthy of further research.

  14. No association of genetic polymorphisms in CYP1B1 with primary open-angle glaucoma: a meta- and gene-based analysis

    PubMed Central

    Dong, Shuqian; Yang, Jingyun; Yu, Weihong; Kota, Pravina; Xia, Xiaobo

    2012-01-01

    Purpose To examine the effects of genetic polymorphisms in cytochrome P450, subfamily 1, polypeptide 1 (C1P1B1) on primary open-angle glaucoma (POAG). Methods A systematic literature search was performed, and random-effects meta-analyses were used to evaluate genetic polymorphisms in CYP1B1 with POAG. A gene-based analysis was conducted to investigate the cumulative effects of genetic polymorphisms in CYP1B1. Results A total of six studies from published papers were included in our analysis. Random-effects meta-analyses failed to detect any significant association of POAG with genetic polymorphisms in CYP1B1, including rs180040, rs1056836, rs10012, rs1056827, rs1056837, and rs2567206. The gene-based analysis indicated that the cumulative effect of genetic polymorphisms in CYP1B1 is not associated with POAG (p>0.50). Conclusions We did not find any evidence of strong association of POAG with CYP1B1 genetic polymorphisms and their cumulative effect. PMID:22509109

  15. Recombinational and physical mapping of the locus for primary open-angle glaucoma (GLC1A) on chromosome 1q23-q25

    SciTech Connect

    Belmouden, A.; Adam, M.F.; De Dinechin, S.D. |

    1997-02-01

    Primary open-angle glaucoma (POAG) is a leading cause of irreversible blindness in industrialized countries. A locus for juvenile-onset POAG, GLC1A, has been mapped to 1q21-q31 in a 9-cM interval. With recombinant haplotypes, we have now reduced the GLC1A interval to a maximum of 3 cM, between the D1S452/NGA1/D1S210 and NGA5 loci. These loci are 2.8 Mb apart on a 4.7-Mb contig that we have completed between the D1S2851 and D1S218 loci and that includes 96 YAC clones and 48 STSs. The new GLC1A interval itself is now covered by 25 YACs, 30 STSs, and 16 restriction enzyme site landmarks. The lack of a NotI site suggests that the region has few CpG islands and a low gene content. This is compatible with its predominant cytogenetic location on the 1q24 G-band. Finally, we have excluded important candidate genes, including genes coding for three ATPases (AMB1, ATP2B4, ATPlA2), an ion channel (VDAC4), antithrombine III (AT3), and prostaglandin synthase (PTGS2). Our results provide a basis to identify the GLC1A gene. 59 refs., 3 figs., 3 tabs.

  16. Recombinational and physical mapping of the locus for primary open-angle glaucoma (GLC1A) on chromosome 1q23-q25.

    PubMed

    Belmouden, A; Adam, M F; Dupont de Dinechin, S; Brézin, A P; Rigault, P; Chumakov, I; Bach, J F; Garchon, H J

    1997-02-01

    Primary open-angle glaucoma (POAG) is a leading cause of irreversible blindness in industrialized countries. A locus for juvenile-onset POAG, GLC1A, has been mapped to 1q21-q31 in a 9-cM interval. With recombinant haplotypes, we have now reduced the GLC1A interval to a maximum of 3 cM, between the D1S452/NGA1/D1S210 and NGA5 loci. These loci are 2.8 Mb apart on a 4.7-Mb contig that we have completed between the D1S2851 and D1S218 loci and that includes 96 YAC clones and 48 STSs. The new GLC1A interval itself is now covered by 25 YACs, 30 STSs, and 16 restriction enzyme site landmarks. The lack of a NotI site suggests that the region has few CpG islands and a low gene content. This is compatible with its predominant cytogenetic location on the 1q24 G-band. Finally, we have excluded important candidate genes, including genes coding for three ATPases (ATP1B1, ATP2B4, ATP1A2), an ion channel (VDAC4), antithrombine III (AT3), and prostaglandin synthase (PTGS2). Our results provide a basis to identify the GLC1A gene.

  17. Ultra-high resolution profiles of macular intra-retinal layer thicknesses and associations with visual field defects in primary open angle glaucoma

    NASA Astrophysics Data System (ADS)

    Chen, Qi; Huang, Shenghai; Ma, Qingkai; Lin, Huiling; Pan, Mengmeng; Liu, Xinting; Lu, Fan; Shen, Meixiao

    2017-02-01

    The structural characteristics of the outer retinal layers in primary open angle glaucoma (POAG) are still controversial, and these changes, along with those in the inner retinal layers, could have clinical and/or pathophysiological significance. A custom-built ultra-high resolution optical coherence tomography (UHR-OCT) combined with an automated segmentation algorithm can image and measure the eight intra-retinal layers. The purpose of this study is to determine the thickness characteristics of the macular intra-retinal layers, especially the outer layers, in POAG patients. Thirty-four POAG patients (56 eyes) and 33 normal subjects (63 eyes) were enrolled. Thickness profiles of the eight intra-retinal layers along a 6-mm length centred on the fovea at the horizontal and vertical meridians were obtained and the regional thicknesses were compared between two groups. The associations between the thicknesses of each intra-retinal layer and the macular visual field (VF) sensitivity were then analysed. POAG affected not only the inner retinal layers but also the photoreceptor layers and retinal pigment epithelium of the outer retina. However, the VF loss was correlated mainly with the damage of the inner retinal layers. UHR-OCT with automated algorithm is a useful tool in detecting microstructural changes of macula with respect to the progression of glaucoma.

  18. Structural and functional brain changes in early- and mid-stage primary open-angle glaucoma using voxel-based morphometry and functional magnetic resonance imaging

    PubMed Central

    Jiang, Ming-Ming; Zhou, Qing; Liu, Xiao-Yong; Shi, Chang-Zheng; Chen, Jian; Huang, Xiang-He

    2017-01-01

    Abstract To investigate structural and functional brain changes in patients with primary open-angle glaucoma (POAG) by using voxel-based morphometry based on diffeomorphic anatomical registration through exponentiated Lie algebra (VBM-DARTEL) and blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI), respectively. Thirteen patients diagnosed with POAG and 13 age- and sex-matched healthy controls were enrolled in the study. For each participant, high-resolution structural brain imaging and blood flow imaging were acquired on a 3.0-Tesla magnetic resonance imaging (MRI) scanner. Structural and functional changes between the POAG and control groups were analyzed. An analysis was carried out to identify correlations between structural and functional changes acquired in the previous analysis and the retinal nerve fiber layer (RNFL). Patients in the POAG group showed a significant (P < 0.001) volume increase in the midbrain, left brainstem, frontal gyrus, cerebellar vermis, left inferior parietal lobule, caudate nucleus, thalamus, precuneus, and Brodmann areas 7, 18, and 46. Moreover, significant (P < 0.001) BOLD signal changes were observed in the right supramarginal gyrus, frontal gyrus, superior frontal gyrus, left inferior parietal lobule, left cuneus, and left midcingulate area; many of these regions had high correlations with the RNFL. Patients with POAG undergo widespread and complex changes in cortical brain structure and blood flow. (ClinicalTrials.gov number: NCT02570867). PMID:28248867

  19. Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucoma.

    PubMed

    Bailey, Jessica N Cooke; Loomis, Stephanie J; Kang, Jae H; Allingham, R Rand; Gharahkhani, Puya; Khor, Chiea Chuen; Burdon, Kathryn P; Aschard, Hugues; Chasman, Daniel I; Igo, Robert P; Hysi, Pirro G; Glastonbury, Craig A; Ashley-Koch, Allison; Brilliant, Murray; Brown, Andrew A; Budenz, Donald L; Buil, Alfonso; Cheng, Ching-Yu; Choi, Hyon; Christen, William G; Curhan, Gary; De Vivo, Immaculata; Fingert, John H; Foster, Paul J; Fuchs, Charles; Gaasterland, Douglas; Gaasterland, Terry; Hewitt, Alex W; Hu, Frank; Hunter, David J; Khawaja, Anthony P; Lee, Richard K; Li, Zheng; Lichter, Paul R; Mackey, David A; McGuffin, Peter; Mitchell, Paul; Moroi, Sayoko E; Perera, Shamira A; Pepper, Keating W; Qi, Qibin; Realini, Tony; Richards, Julia E; Ridker, Paul M; Rimm, Eric; Ritch, Robert; Ritchie, Marylyn; Schuman, Joel S; Scott, William K; Singh, Kuldev; Sit, Arthur J; Song, Yeunjoo E; Tamimi, Rulla M; Topouzis, Fotis; Viswanathan, Ananth C; Verma, Shefali Setia; Vollrath, Douglas; Wang, Jie Jin; Weisschuh, Nicole; Wissinger, Bernd; Wollstein, Gadi; Wong, Tien Y; Yaspan, Brian L; Zack, Donald J; Zhang, Kang; Study, Epic-Norfolk Eye; Weinreb, Robert N; Pericak-Vance, Margaret A; Small, Kerrin; Hammond, Christopher J; Aung, Tin; Liu, Yutao; Vithana, Eranga N; MacGregor, Stuart; Craig, Jamie E; Kraft, Peter; Howell, Gareth; Hauser, Michael A; Pasquale, Louis R; Haines, Jonathan L; Wiggs, Janey L

    2016-02-01

    Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide. To identify new susceptibility loci, we performed meta-analysis on genome-wide association study (GWAS) results from eight independent studies from the United States (3,853 cases and 33,480 controls) and investigated the most significantly associated SNPs in two Australian studies (1,252 cases and 2,592 controls), three European studies (875 cases and 4,107 controls) and a Singaporean Chinese study (1,037 cases and 2,543 controls). A meta-analysis of the top SNPs identified three new associated loci: rs35934224[T] in TXNRD2 (odds ratio (OR) = 0.78, P = 4.05 × 10(-11)) encoding a mitochondrial protein required for redox homeostasis; rs7137828[T] in ATXN2 (OR = 1.17, P = 8.73 × 10(-10)); and rs2745572[A] upstream of FOXC1 (OR = 1.17, P = 1.76 × 10(-10)). Using RT-PCR and immunohistochemistry, we show TXNRD2 and ATXN2 expression in retinal ganglion cells and the optic nerve head. These results identify new pathways underlying POAG susceptibility and suggest new targets for preventative therapies.

  20. Exome Sequencing Identifies a Missense Variant in EFEMP1 Co-Segregating in a Family with Autosomal Dominant Primary Open-Angle Glaucoma

    PubMed Central

    Mackay, Donna S.; Bennett, Thomas M.; Shiels, Alan

    2015-01-01

    Primary open-angle glaucoma (POAG) is a clinically important and genetically heterogeneous cause of progressive vision loss as a result of retinal ganglion cell death. Here we have utilized trio-based, whole-exome sequencing to identify the genetic defect underlying an autosomal dominant form of adult-onset POAG segregating in an African-American family. Exome sequencing identified a novel missense variant (c.418C>T, p.Arg140Trp) in exon-5 of the gene coding for epidermal growth factor (EGF) containing fibulin-like extracellular matrix protein 1 (EFEMP1) that co-segregated with disease in the family. Linkage and haplotype analyses with microsatellite markers indicated that the disease interval overlapped a known POAG locus (GLC1H) on chromosome 2p. The p.Arg140Trp substitution was predicted in silico to have damaging effects on protein function and transient expression studies in cultured cells revealed that the Trp140-mutant protein exhibited increased intracellular accumulation compared with wild-type EFEMP1. In situ hybridization of the mouse eye with oligonucleotide probes detected the highest levels of EFEMP1 transcripts in the ciliary body, cornea, inner nuclear layer of the retina, and the optic nerve head. The recent finding that a common variant near EFEMP1 was associated with optic nerve-head morphology supports the possibility that the EFEMP1 variant identified in this POAG family may be pathogenic. PMID:26162006

  1. Ultra-high resolution profiles of macular intra-retinal layer thicknesses and associations with visual field defects in primary open angle glaucoma

    PubMed Central

    Chen, Qi; Huang, Shenghai; Ma, Qingkai; Lin, Huiling; Pan, Mengmeng; Liu, Xinting; Lu, Fan; Shen, Meixiao

    2017-01-01

    The structural characteristics of the outer retinal layers in primary open angle glaucoma (POAG) are still controversial, and these changes, along with those in the inner retinal layers, could have clinical and/or pathophysiological significance. A custom-built ultra-high resolution optical coherence tomography (UHR-OCT) combined with an automated segmentation algorithm can image and measure the eight intra-retinal layers. The purpose of this study is to determine the thickness characteristics of the macular intra-retinal layers, especially the outer layers, in POAG patients. Thirty-four POAG patients (56 eyes) and 33 normal subjects (63 eyes) were enrolled. Thickness profiles of the eight intra-retinal layers along a 6-mm length centred on the fovea at the horizontal and vertical meridians were obtained and the regional thicknesses were compared between two groups. The associations between the thicknesses of each intra-retinal layer and the macular visual field (VF) sensitivity were then analysed. POAG affected not only the inner retinal layers but also the photoreceptor layers and retinal pigment epithelium of the outer retina. However, the VF loss was correlated mainly with the damage of the inner retinal layers. UHR-OCT with automated algorithm is a useful tool in detecting microstructural changes of macula with respect to the progression of glaucoma. PMID:28169283

  2. Fixed combination of travoprost and timolol maleate reduces intraocular pressure in Japanese patients with primary open-angle glaucoma or ocular hypertension: analysis by prostaglandin analogue

    PubMed Central

    Nakano, Tadashi; Mizoue, Shiro; Fuse, Nobuo; Iwase, Aiko; Matsumoto, Shun; Yoshikawa, Keiji

    2017-01-01

    Background We have shown a decrease in mean intraocular pressure (IOP) by switching to travoprost/timolol fixed combination (TTFC) in subjects receiving prostaglandin analogue (PGA) monotherapy and requiring additional medication in a previous report. For analyzing factors affecting IOP reduction, baseline IOP and preceding PGA were selected as statistically and clinically significant factors. In this report, we examine IOP-lowering effect and adverse drug reactions by preceding PGA. Methods Patients with primary open angle glaucoma or ocular hypertension who received monotherapy with one of four PGAs (travoprost, latanoprost, tafluprost, or bimatoprost) for at least 3 months at 26 institutions and were determined to require additional medication by their primary physician were included. IOP reduction and adverse events were examined at 4, 8, and 12 weeks for each of four PGAs after switching to TTFC. Results In total, 157 patients who could be followed up for at least 4 weeks after switching to TTFC were included in the efficacy analysis. Multiple regression analysis was performed, and baseline IOP and PGA were found to be significant factors to IOP reduction. IOP reduction at week 12, adjusted with the regression model, was −3.5, −1.8, and −1.4 mmHg in the tafluprost, latanoprost, and travoprost groups, whereas it was −0.5 mmHg in the bimatoprost group. Along with differences in baseline IOP between groups, an IOP-lowering effect of >1 mmHg was noted in the tafluprost, latanoprost, and travoprost groups after the switch. IOP was maintained at 13.8–14.8 mmHg throughout the follow-up period. No serious adverse events or noteworthy issues were observed in any group after the switch. Conclusion Clinically significant IOP-reducing effects of TTFC were observed in the latanoprost, travoprost, and tafluprost groups when switching from each PGA monotherapy, while there were some differences in effects between groups, with minimal safety concerns. PMID:28053501

  3. Efficacy of Garcinia kola 0.5% Aqueous Eye Drops in Patients with Primary Open-Angle Glaucoma or Ocular Hypertension

    PubMed Central

    Adefule-Ositelu, Adebukunola O.; Adegbehingbe, Bernice O.; Adefule, Adebayo K.; Adegbehingbe, Olayinka O.; Samaila, Elsie; Oladigbolu, Kehinde

    2010-01-01

    Purpose: To evaluate the intraocular pressure (IOP) lowering efficacy of Garcinia kola 0.5% aqueous solution eye drops in patients with newly diagnosed primary open-angle glaucoma or ocular hypertension (POAG/OH). Materials and Methods: A randomized, double-masked, multicenter, active-controlled prospective study. Patients who met the inclusion criteria were randomly assigned in equal numbers to receive Timolol 0.5% eye drops as a control medication (A = Group 1 eyes) or Garcinia kola 0.5% eye drops as the study medication (B = Group 2 eyes). All drops were instilled at 6 am and 6 pm daily. Goldman applanation tonometry was performed at 9 am, 12 pm and 3 pm at baseline, week-6, week-12 and week-24 visits. Voluntary and actively elicited reports of adverse events were documented. The mean change in IOP over 24 weeks was the primary outcome measure. Both groups were compared for statistically significant differences at all visits. A P < 0.05 was considered statistically significant. Results: A total of 178 patients were randomly assigned to G. kola and Timolol groups. At baseline there were no differences in mean IOP between groups, based on age, sex, or diagnosis. At the end of the study period (24th week), the mean (± SD) reduction in IOP was 12.93 ± 2.3 mmHg (47.8% ± 0.8% reduction) in G. Kola group and 13.09 ± 2.8 mm Hg (48.2% ± 1.03% reduction) in the Timolol group (P > 0.05). Adverse events were mild in nature with no statistically significant differences between groups (P > 0.05). Conclusions: Garcinia kola ophthalmic solution significantly reduces IOP as compared to baseline. The IOP lowering effect of both treatments was equivalent. PMID:20543944

  4. Clinical effectiveness of brinzolamide 1%–brimonidine 0.2% fixed combination for primary open-angle glaucoma and ocular hypertension

    PubMed Central

    Sharma, Sourabh; Trikha, Sameer; Perera, Shamira A; Aung, Tin

    2015-01-01

    The main first-line treatment strategy for glaucoma is to reduce intraocular pressure (IOP) by topical ocular hypotensive medications, but many patients require multiple medications for adequate IOP control. Fixed-combination therapies provide several benefits, including simplified treatment regimens, theoretical improved treatment adherence, elimination of the potential for washout of the first drug by the second, and the reduction in ocular exposure to preservatives. β-Adrenoceptor antagonists (particularly 0.5% timolol) are the most commonly used agents in combination with other classes of drugs as fixed-combination eyedrops, but they are contraindicated in many patients, owing to local allergy or systemic side effects. A fixed-combination preparation without a β-blocker is therefore warranted. This paper reviews the clinical effectiveness of brinzolamide 1% and brimonidine 0.2% fixed combination (BBFC) for use in patients with primary open-angle glaucoma and ocular hypertension. We searched PubMed and the ClinicalTrials.gov registry, and identified three randomized controlled trials comparing BBFC vs its constituents (brimonidine vs brinzolamide), and one comparing BBFC with unfixed brimonidine and brinzolamide. All of the studies demonstrated mean diurnal IOP to be statistically significantly lower in the BBFC group compared with constituent groups and noninferior to that with the concomitant group using two separate bottles. The safety profile of BBFC was consistent with that of its individual components, the most common ocular adverse events being ocular hyperemia, visual disturbances, and ocular allergic reactions. Common systemic adverse effects included altered taste sensation, oral dryness, fatigue, somnolence, and decreased alertness. BBFC seems to be a promising new fixed combination for use in glaucoma patients. However, long-term effects of BBFC on IOP, treatment adherence, and safety need to be determined. PMID:26648686

  5. Comparison of vision-related quality of life in primary open-angle glaucoma and dry-type age-related macular degeneration.

    PubMed

    Karadeniz Ugurlu, S; Kocakaya Altundal, A E; Altin Ekin, M

    2017-03-01

    PurposeTo compare quality of life (QoL) in patients with primary open-angle glaucoma (POAG) and dry-type age-related macular degeneration (AMD) with similar best-corrected visual acuity.MethodsAge-, sex-, and visual acuity-matched POAG and dry AMD patients were included in the study. Each patient performed 24-2 and 10-2 SITA standard visual field tests. Contrast sensitivity was evaluated with CSV-1000 HGT instrument. The 25 item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) was used to analyze QoL. Overall and subscale scores were converted to scores between 0 and 100, the higher scores indicating better vision-related QoL.ResultsOverall NEI-VFQ-25 scores were 86.44 and 84.66 in glaucoma and AMD groups, respectively (P=0.244). The highest scores were obtained in 'vision-related dependency' subgroup in glaucoma and 'color and peripheral vision' in AMD group, whereas the lowest scores were noted 'in peripheral vision' in both glaucoma and AMD patients. Glaucoma patients had significantly lower scores in ocular pain, color vision, and peripheral vision subgroups compared with the AMD group, whereas AMD patients had lower scores in near and distance vision activities, vision-related social activity, and dependency subgroups. Contrast sensitivity results and mean defect values showed correlation with NEI-VFQ-25 scores in both groups.ConclusionsGlaucoma and AMD patients with similar visual acuity experienced similar overall impairment in QoL. However, glaucoma patients described more difficulty with peripheral vision and ocular pain, whereas AMD patients complained more about near and distance vision and dependency items.

  6. Genetic Variants Associated with Optic Nerve Vertical Cup-to-Disc Ratio Are Risk Factors for Primary Open Angle Glaucoma in a US Caucasian Population

    PubMed Central

    Fan, Bao Jian; Wang, Dan Yi; Pasquale, Louis R.; Haines, Jonathan L.

    2011-01-01

    Purpose. Genetically complex disorders, such as primary open angle glaucoma (POAG), may include highly heritable quantitative traits as part of the overall phenotype, and mapping genes influencing the related quantitative traits may effectively identify genetic risk factors predisposing to the complex disease. Recent studies have identified SNPs associated with optic nerve area and vertical cup-to-disc ratio (VCDR). The purpose of this study was to evaluate the association between these SNPs and POAG in a US Caucasian case-control sample. Methods. Five SNPs previously associated with optic disc area, or VCDR, were genotyped in 539 POAG cases and 336 controls. Genotype data were analyzed for single SNP associations and SNP interactions with VCDR and POAG. Results. SNPs associated with VCDR rs1063192 (CDKN2B) and rs10483727 (SIX1/SIX6) were also associated with POAG (P = 0.0006 and P = 0.0043 for rs1063192 and rs10483727, respectively). rs1063192, associated with smaller VCDR, had a protective effect (odds ratio [OR] = 0.73; 95% confidence interval [CI], 0.58–0.90), whereas rs10483727, associated with larger VCDR, increased POAG risk (OR = 1.33; 95% CI, 1.08–1.65). POAG risk associated with increased VCDR was significantly influenced by the C allele of rs1900004 (ATOH7), associated with increased optic nerve area (P-interaction = 0.025; OR = 1.89; 95% CI, 1.22–2.94). Conclusions. Genetic variants influencing VCDR are associated with POAG in a US Caucasian population. Variants associated with optic nerve area are not independently associated with disease but can influence the effects of VCDR variants suggesting that increased optic disc area can significantly contribute to POAG risk when coupled with risk factors controlling VCDR. PMID:21398277

  7. Choroidal area assessment in various fundus sectors of patients at different stages of primary open-angle glaucoma by using enhanced depth imaging optical coherence tomography

    PubMed Central

    Li, Mu; Yan, Xiao-Qin; Song, Yin-Wei; Guo, Jing-Min; Zhang, Hong

    2017-01-01

    Abstract To compare the choroidal area in different eye fundus sectors of subjects with normal eyes, early-stage primary open-angle glaucoma (POAG) eyes, and 10° tubular visual field POAG eyes using enhanced depth imaging optical coherence tomography. Twenty-five normal, 25 early-stage POAG, and 25 ten-degree tubular visual field POAG eyes were recruited. Enhanced depth imaging optical coherence tomography was used to measure the choroidal area in different fundus sectors (fovea; 10° superior, inferior, temporal, and 24° superior, inferior, temporal, nasal to the fovea) and the peripapillary sector. There were neither significant differences in the choroidal area at any of the 8 measured fundus sectors, nor significant differences in the percentage change between the choroidal area of the fovea and other 7 measured fundus sectors among the 3 groups (all P > 0.05). For the total peripapillary choroidal area, no significant difference was found among the 3 groups (P > 0.05); however, the temporal peripapillary choroidal area of 10° tubular visual field POAG eyes was significantly thicker than that of normal eyes (4,46,213 ± 1,16,267 vs 3,74,164 ± 1,21,658 μm2; P = 0.048). Our study showed that there was no significant difference in the choroidal area of the 8 measured fundus sectors among normal, early-stage POAG, and 10° tubular visual field POAG eyes, suggesting that there might be no blood redistribution from the peripheral choroid to the subfoveal choroid. However, the thicker temporal peripapillary choroidal area might play a role in the central visual acuity protection in patients with POAG. PMID:28272255

  8. Polymorphism of CYP46A1 and PPARγ2 Genes in Risk Prediction of Primary Open Angle Glaucoma Among North Indian Population

    PubMed Central

    Chandra, Anu; Abbas, Shania; Raza, Syed Tasleem; Singh, Luxmi; Rizvi, Saliha; Mahdi, Farzana

    2016-01-01

    Purpose: Glaucoma is the leading cause of irreversible blindness and the second most common cause of all blindness after cataracts. This study investigates the association of polymorphism in the CYP46A1 and PPARγ2 genes and primary open angle glaucoma (POAG). Materials and Methods: This study evaluated 122 POAG cases (POAG group) and 112 cases of nonglaucomatous patients (control group). Polymorphisms of the CYP46A1 gene and PPARγ2 gene were evaluated with the polymerase chain reaction-restriction fragment length polymorphism method in both groups. Results: The mean ages were 49.88 ± 12.34 years and 53.74 ± 11.87 years for the POAG group and control group, respectively. The CYP46A1 gene CC, CT, TT genotype frequencies were 13.93%, 58.2%, 27.87% in the POAG group and 19.6%, 40.19%, 40.19% in the control group, respectively. The PPARγ2 gene CC, CG, GG genotype frequencies were 16.83%, 54.45%, 28.71% in cases and 3.92%, 28.43%, 67.64% in the control group, respectively. Statistically, significant differences in the frequencies of CYP46A1 CC, CT, TT and PPARγ2 CC, CG, GG (P < 0.05) genotype were found between groups (P < 0.05, all comparisons). Conclusion: Findings of this study suggest that CYP46A1 gene and PPARγ2 gene polymorphisms can be a predictive marker for early identification of population at risk of POAG, although a larger sample size is required to determine the role of these polymorphisms in the pathogenesis and course of POAG. PMID:27162448

  9. Association of single nucleotide polymorphisms in the CYP1B1 gene with the risk of primary open-angle glaucoma: a meta-analysis.

    PubMed

    Wang, Z; Li, M; Li, L; Sun, H; Lin, X Y

    2015-12-17

    Mutations in the CYP1B1 gene were detected in primary open-angle glaucoma (POAG) patients. However, the association between these mutations and the incidence of POAG remains to be elucidated. Here, we have conducted a meta-analysis to analyze this correlation, using relevant studies obtained from an extensive search of various electronic databases, including EMBase, Web of Science, and PubMed. The extracted studies were selected for the meta-analysis based on the inclusion and exclusion criteria. The quality of each included study was assessed by the Newcastle-Ottawa scale (NOS), and the I2 value was calculated to evaluate the heterogeneity between studies. The combined effect size was presented as the odds ratio (OR), and confidence intervals (CI) were used to assess the association between POAG and CYP1B1 mutations. Eight studies, each with a high NOS score, were included in the analysis. Compared to the mutant allele, the wild-type allele of the rs180040 polymorphism in POAG patients showed a 12% decrease in OR (OR = 0.88, 95%CI = 0.76- 1.00); also, the wild-type allele of rs1056827 showed a 23% decrease in OR of the incidence of POAG (OR = 0.77, 95%CI = 0.60-0.99). However, the latter result was controversial. Polymorphisms at rs1056836, rs10012, and rs1056837 were not correlated with the incidence of POAG (using any evaluation model). In conclusion, three of the tested SNPs in the CYP1B1 gene were correlated with POAG; however, the SNPs rs180040 and rs1056827 showed an association with risk of POAG. These results must be further validated with larger-scale evaluations.

  10. Comparison of Risk Factor Profiles for Primary Open-Angle Glaucoma Subtypes Defined by Pattern of Visual Field Loss: A Prospective Study

    PubMed Central

    Kang, Jae H.; Loomis, Stephanie J.; Rosner, Bernard A.; Wiggs, Janey L.; Pasquale, Louis R.

    2015-01-01

    Purpose. We explored whether risk factor associations differed by primary open-angle glaucoma (POAG) subtypes defined by visual field (VF) loss pattern (i.e., paracentral or peripheral). Methods. We included 77,157 women in the Nurses' Health Study (NHS) and 42,773 men in the Health Professionals Follow-up Study (HPFS 1986–2010), and incident medical record confirmed cases of paracentral (n = 440) and peripheral (n = 865) POAG subtypes. We evaluated African heritage, glaucoma family history, body mass index (BMI), mean arterial blood pressure, diabetes mellitus, physical activity, smoking, caffeine intake, and alcohol intake. We used competing risk Cox regression analyses modeling age as the metameter and stratified by age, cohort, and event type. We sequentially identified factors with the least significant differences in associations with POAG subtypes (“stepwise down” approach with P for heterogeneity [P-het] < 0.10 as threshold). Results. Body mass index was more inversely associated with the POAG paracentral VF loss subtype than the peripheral VF loss subtype (per 10 kg/m2; hazard ratio [HR] = 0.67 [95% confidence interval (CI): 0.52, 0.86] versus HR = 0.93 [95% CI: 0.78, 1.10]; P-het = 0.03) as was smoking (per 10 pack-years; HR = 0.92 [95% CI: 0.87, 0.98] versus HR = 0.98 [95% CI: 0.94, 1.01]; P-het = 0.09). These findings were robust in sensitivity analyses using a “stepwise up” approach (identify factors that showed the most significant differences). Nonheterogeneous (P-het > 0.10) adverse associations with both POAG subtypes were observed with glaucoma family history, diabetes, African heritage, greater caffeine intake, and higher mean arterial pressure. Conclusions. These data indicate that POAG with early paracentral VF loss has distinct as well as common determinants compared with POAG with peripheral VF loss. PMID:25758813

  11. A comparison of the diagnostic ability of vessel density and structural measurements of optical coherence tomography in primary open angle glaucoma

    PubMed Central

    Pradhan, Zia S.; Weinreb, Robert N.; Riyazuddin, Mohammed; Dasari, Srilakshmi; Venugopal, Jayasree P.; Puttaiah, Narendra K.; Rao, Dhanaraj A. S.; Devi, Sathi; Mansouri, Kaweh; Webers, Carroll A. B.

    2017-01-01

    Purpose To compare the diagnostic abilities of vessel density measurements of the optic nerve head (ONH), peripapillary and macular regions on optical coherence tomography (OCT) angiography in eyes with primary open angle glaucoma (POAG) with that of the ONH rim area, peripapillary retinal nerve fiber layer (RNFL) thickness and the macular ganglion cell complex (GCC) thickness measurements. Methods In a cross sectional study, 78 eyes of 50 control subjects and 117 eyes of 67 POAG patients underwent vessel density and structural measurements with spectral domain OCT. POAG was diagnosed based on the masked evaluation of optic disc stereo photographs. Area under receiver operating characteristic curves (AUC) and sensitivities at fixed specificities of vessel densities in ONH, peripapillary and macular regions were compared with rim area, RNFL and GCC thickness. Results The AUC (sensitivity at 95% specificity) of average vessel densities within the ONH, peripapillary and macular region were 0.77 (31%), 0.85 (56%) and 0.70 (18%) respectively. The same of ONH rim area, average RNFL and GCC thickness were 0.94 (83%), 0.95 (72%) and 0.93 (62%) respectively. AUCs of vessel densities were significantly lower (p<0.05) than that of the corresponding structural measurements. Pre-treatment IOP (coefficient: 0.08) affected (p<0.05) the AUC of ONH vessel density but not of any other vessel density or structural measurements. Conclusions Diagnostic abilities of ONH, peripapillary and the macular vessel densities in POAG were significantly lower than ONH rim area, peripapillary RNFL and macular GCC measurements respectively. At fixed levels of glaucoma severity, the diagnostic ability of the ONH vessel density was significantly greater in eyes with higher pre-treatment IOP. PMID:28288185

  12. The impact of chronic use of prostaglandin analogues on the biomechanical properties of the cornea in patients with primary open-angle glaucoma

    PubMed Central

    Meda, Roman; Wang, Qianqian; Paoloni, David; Harasymowycz, Paul; Brunette, Isabelle

    2017-01-01

    Aims To determine the influence of prostaglandin analogues (PGAs) on corneal biomechanical properties in patients undergoing chronic treatment for primary open-angle glaucoma (POAG). Methods Prospective, interventional case–control study. 70 eyes from 35 patients with POAG on chronic PGA therapy were recruited. One eye per patient underwent PGA cessation for 6 weeks while the contralateral eye continued to receive the treatment. Corneal hysteresis (CH), corneal resistance factor (CRF), corneal-compensated intraocular pressure (IOP) (IOPcc), central corneal thickness (CCT) and Goldmann tonometry (Haag-Streit AG, Koeniz, Switzerland) IOP (IOPGAT) were measured at baseline (visit 1), 6 weeks after PGA cessation (visit 2) and 6 weeks after PGAs reinitiation (visit 3) and were analysed using a linear mixed-effect model. The discrepancy between IOPcc and IOPGAT was defined as IOP bias (IOPcc—IOPGAT). Results Baseline characteristics were comparable between the two groups. In the study eyes, significant increases (p<0.0001) were detected at visit 2 in CH (9.0±1.8 vs 10.3±1.7 mm Hg), CRF (10.5±2.1 vs 11.7±2.1 mm Hg), CCT (541.8±43.2 vs 551.9±41.9 μm) and IOPGAT (15.4±3.0 vs 18.4±3.8 mm Hg). IOP bias in this group was significantly lowered at visit 2 (p<0.0001). These effects were reversed at visit 3. The control eyes did not demonstrate any significant changes over the study period. Conclusion Topical PGAs induce reversible reduction in CH, CRF and CCT in patients with POAG. These changes contribute to underestimation of the IOP measured by Goldmann applanation tonometry and warrant caution when assessing response to treatment. Trial registration number NCT02388360, Results. PMID:27162226

  13. Global variations and time trends in the prevalence of primary open angle glaucoma (POAG): a systematic review and meta-analysis

    PubMed Central

    Kapetanakis, Venediktos V; Chan, Michelle P Y; Foster, Paul J; Cook, Derek G; Owen, Christopher G; Rudnicka, Alicja R

    2016-01-01

    Systematic review of published population based surveys to examine the relationship between primary open angle glaucoma (POAG) prevalence and demographic factors. A literature search identified population-based studies with quantitative estimates of POAG prevalence (to October 2014). Multilevel binomial logistic regression of log-odds of POAG was used to examine the effect of age and gender among populations of different geographical and ethnic origins, adjusting for study design factors. Eighty-one studies were included (37 countries, 216 214 participants, 5266 POAG cases). Black populations showed highest POAG prevalence, with 5.2% (95% credible interval (CrI) 3.7%, 7.2%) at 60 years, rising to 12.2% (95% CrI 8.9% to 16.6%) at 80 years. Increase in POAG prevalence per decade of age was greatest among Hispanics (2.31, 95% CrI 2.12, 2.52) and White populations (1.99, 95% CrI 1.86, 2.12), and lowest in East and South Asians (1.48, 95% CrI 1.39, 1.57; 1.56, 95% CrI 1.31, 1.88, respectively). Men were more likely to have POAG than women (1.30, 95% CrI 1.22, 1.41). Older studies had lower POAG prevalence, which was related to the inclusion of intraocular pressure in the glaucoma definition. Studies with visual field data on all participants had a higher POAG prevalence than those with visual field data on a subset. Globally 57.5 million people (95% CI 46.4 to 73.1 million) were affected by POAG in 2015, rising to 65.5 million (95% CrI 52.8, 83.2 million) by 2020. This systematic review provides the most precise estimates of POAG prevalence and shows omitting routine visual field assessment in population surveys may have affected case ascertainment. Our findings will be useful to future studies and healthcare planning. PMID:26286821

  14. Comparative Effectiveness of First-line Medications for Primary Open Angle Glaucoma – A Systematic Review and Network Meta-analysis

    PubMed Central

    Li, Tianjing; Lindsley, Kristina; Rouse, Benjamin; Hong, Hwanhee; Shi, Qiyuan; Friedman, David S.; Wormald, Richard; Dickersin, Kay

    2015-01-01

    Topic Primary open angle glaucoma (POAG) is a highly prevalent condition worldwide and the most common cause of irreversible sight loss. The objective is to assess the comparative effectiveness of first line medical treatments in patients with POAG or ocular hypertension through a systematic review and network meta-analysis, and to provide relative rankings of these treatments. Clinical Relevance Treatment for POAG currently relies completely on lowering the intraocular pressure (IOP). While topical drops, lasers, and surgeries can be considered in the initial treatment of glaucoma, most patients elect to start treatment with eye drops. Methods We included randomized controlled trials that compared a single active topical medication with no treatment/placebo or another single topical medication. We searched CENTRAL, MEDLINE, EMBASE and the Food and Drug Administration's website. Two individuals independently assessed trial eligibility, abstracted data, and assessed the risk of bias. We performed Bayesian network meta-analyses. Results We included 114 randomized controlled trials with data from 20,275 participants. The overall risk of bias of the included trials is mixed. The mean reductions (95% credible intervals) in IOP in mmHg at 3 months, ordered from the most to least effective drugs were: bimatoprost 5·61 (4·94; 6·29), latanoprost 4·85 (4·24; 5·46), travoprost 4·83 (4·12; 5·54), levobunolol 4·51 (3·85; 5·24), tafluprost 4·37 (2·94; 5·83), timolol 3·7 (3·16; 4·24), brimonidine 3·59 (2·89; 4·29), carteolol 3·44 (2·42; 4·46), levobetaxolol 2·56 (1·52; 3·62), apraclonidine 2·52 (0·94; 4·11), dorzolamide 2·49 (1·85; 3·13), brinzolamide 2·42 (1·62; 3·23), betaxolol 2·24 (1·59; 2·88), and unoprostone 1·91 (1·15; 2·67). Conclusions All active first-line drugs are effective compared to placebo in reducing IOP at 3 months. Bimatoprost, latanoprost, and travoprost are among the most efficacious drugs, although the within class

  15. Baseline factors predicting the risk of conversion from ocular hypertension to primary open-angle glaucoma during a 10-year follow-up.

    PubMed

    Salvetat, M L; Zeppieri, M; Tosoni, C; Brusini, P

    2016-06-01

    PurposeTo evaluate the ability of baseline clinical, morphological, and functional factors to predict the conversion to primary open-angle glaucoma (POAG) in ocular hypertensive (OHT) patients.MethodsThis single-center prospective longitudinal observational study included 116 eyes of 116 OHT patients followed for a 10-year period. All patients had intraocular pressure (IOP) ≥24 mm Hg in one eye and >21 mm Hg in the other eye, normal visual fields (VFs) and normal optic disc (OD) appearance in both eyes at baseline. All OHT patients were untreated at baseline with subsequent treatment upon need according to clinical judgement. Only one eye per subject was randomly selected. Patient age, gender, IOP, central corneal thickness (CCT), and ibopamine test results were collected at baseline. All patients underwent standard automated perimetry, short-wavelength automated perimetry (SWAP), frequency-doubling technology, confocal scanning laser ophthalmoscopy (CSLO), and scanning laser polarimetry (SLP) at baseline and every 6 months thereafter. Main outcome measure was the conversion to POAG, defined as the development of reproducible VF and/or OD abnormalities attributable to glaucoma. Cox proportional hazards models were used to identify the baseline factors predictive of POAG conversion.ResultsDuring the 10-year follow-up, 25% of eyes converted to POAG. In multivariate Cox models, baseline factors that were significant predictors of POAG development included: older age (hazard ratio (HR) 1.0, 99% confidence intervals (CIs) 1.0-1.2, per 1 year older); SWAP Glaucoma Hemifield test 'outside normal limits' (HR 4.3, 99% CIs 1.2-17.9); greater SLP 'Inter-eye Symmetry' (HR 1.1, 99% CIs 0.4-3.0, per 1 unit lower); lower CSLO Rim Volume (HR 1.1, 99% CIs 0.3-3.2, per 0.1 mm(3) lower); and greater CSLO cup-to-disc ratio (HR 6.0, 99% CIs 3.6-16.8, per 0.1 unit greater).ConclusionsThe baseline parameters that proved to be useful in assessing the likelihood of an OHT

  16. Factors Influencing the Placebo Effect in Patients with Primary Open-Angle Glaucoma or Ocular Hypertension: An Analysis of Two Randomized Clinical Trials

    PubMed Central

    Kawamura, Taichi; Sato, Izumi; Kawakami, Koji

    2016-01-01

    Objective To explore factors related to the placebo effect in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OH). Methods This was a retrospective cohort study of patients with POAG and patients with OH who were treated with placebo. The patients’ data were extracted from two randomized, double-masked, parallel, multicenter clinical trials (trial 1 and trial 2) in Japan. We explored the baseline factors that were associated with the intraocular pressure (IOP)-lowering effect of placebo ophthalmic solution after 4 weeks of instillation treatment at two time points by using multivariable models. The time points were Hour 0 (between 08:30 and 10:30 before instillation) and Hour 2 (within 1.5 to 2.5 h after instillation and by 12:30) at the baseline date and after 4 weeks. The changes in IOP from baseline to 4 weeks at the two time points were evaluated for the IOP-lowering effect induced by placebo instillation. Results Of the 330 patients included in the two trials, 89 patients were eligible for the analysis. The results of the multivariable analysis for Hour 0 indicated a high IOP at the baseline date (coefficient: 0.24, 95% confidence interval (CI): 0.02 to 0.46, P = 0.03), and the magnitude of the IOP fluctuation at the baseline date (coefficient: 0.57, 95% CI: 0.24 to 0.90, P = 0.001) was associated with the IOP-lowering effect after 4 weeks. With respect to Hour 2, the trial type was associated with the IOP-lowering effect (coefficient: -1.15, 95% CI: -2.14 to -0.16, P = 0.02). Conclusions A large fluctuation in IOP during the day is associated with the IOP-lowering effect induced by placebo in patients with POAG or OH. This finding would be helpful to researchers when designing studies related to glaucoma in the early stages of clinical development of drugs. PMID:27254076

  17. Age at natural menopause genetic risk score in relation to age at natural menopause and primary open-angle glaucoma in a US-based sample

    PubMed Central

    Pasquale, Louis R.; Aschard, Hugues; Kang, Jae H.; Bailey, Jessica N. Cooke; Lindström, Sara; Chasman, Daniel I.; Christen, William G.; Allingham, R. Rand; Ashley-Koch, Allison; Lee, Richard K.; Moroi, Sayoko E.; Brilliant, Murray H.; Wollstein, Gadi; Schuman, Joel S.; Fingert, John; Budenz, Donald L.; Realini, Tony; Gaasterland, Terry; Gaasterland, Douglas; Scott, William K.; Singh, Kuldev; Sit, Arthur J.; Igo, Robert P.; Song, Yeunjoo E.; Hark, Lisa; Ritch, Robert; Rhee, Douglas J.; Gulati, Vikas; Havens, Shane; Vollrath, Douglas; Zack, Donald J.; Medeiros, Felipe; Weinreb, Robert N.; Pericak-Vance, Margaret A.; Liu, Yutao; Kraft, Peter; Richards, Julia E.; Rosner, Bernard A.; Hauser, Michael A.; Haines, Jonathan L.; Wiggs, Janey L.

    2017-01-01

    Abstract Objective: Several attributes of female reproductive history, including age at natural menopause (ANM), have been related to primary open-angle glaucoma (POAG). We assembled 18 previously reported common genetic variants that predict ANM to determine their association with ANM or POAG. Methods: Using data from the Nurses’ Health Study (7,143 women), we validated the ANM weighted genetic risk score in relation to self-reported ANM. Subsequently, to assess the relation with POAG, we used data from 2,160 female POAG cases and 29,110 controls in the National Eye Institute Glaucoma Human Genetics Collaboration Heritable Overall Operational Database (NEIGHBORHOOD), which consists of 8 datasets with imputed genotypes to 5.6+ million markers. Associations with POAG were assessed in each dataset, and site-specific results were meta-analyzed using the inverse weighted variance method. Results: The genetic risk score was associated with self-reported ANM (P = 2.2 × 10–77) and predicted 4.8% of the variance in ANM. The ANM genetic risk score was not associated with POAG (Odds Ratio (OR) = 1.002; 95% Confidence Interval (CI): 0.998, 1.007; P = 0.28). No single genetic variant in the panel achieved nominal association with POAG (P ≥0.20). Compared to the middle 80 percent, there was also no association with the lowest 10th percentile or highest 90th percentile of genetic risk score with POAG (OR = 0.75; 95% CI: 0.47, 1.21; P = 0.23 and OR = 1.10; 95% CI: 0.72, 1.69; P = 0.65, respectively). Conclusions: A genetic risk score predicting 4.8% of ANM variation was not related to POAG; thus, genetic determinants of ANM are unlikely to explain the previously reported association between the two phenotypes. PMID:27760082

  18. Association of dietary nitrate intake with primary open-angle glaucoma: a prospective analysis from the Nurses' Health Study and Health Professionals Follow-up Study

    PubMed Central

    Kang, Jae H.; Willett, Walter C.; Rosner, Bernard; Buys, Emmanuel; Wiggs, Janey L.; Pasquale, Louis R.

    2016-01-01

    Importance Nitric oxide (NO) signaling alterations in outflow facility and retinal blood flow autoregulation are implicated in primary open-angle glaucoma (POAG). NO donation has emerged as a POAG therapeutic target. An exogenous source of NO is dietary nitrates. Objective We evaluated the association between dietary nitrate intake, derived mainly from green leafy vegetables, and POAG. Design, Setting, Participants We followed biennially participants of the prospective cohorts, Nurses' Health Study (63,893 women; 1984-2012) and Health Professionals Follow-up Study (41,094 men; 1986-2012); at each 2-year risk period, eligible participants were 40+ years old, free of POAG, and reported eye examinations. Exposure Dietary nitrate intake. Information on diet and potential confounders were updated with validated questionnaires. Main outcome measure Incidence of POAG and POAG subtypes; 1,483 cases were confirmed with medical records and classified into subtypes defined by intraocular pressure (IOP) (≥ or < 22 mm Hg) or by visual field (VF) loss pattern at diagnosis (peripheral loss only or early paracentral loss). Cohort-specific and pooled multivariable rate ratios (MVRR) and 95% confidence intervals (CIs) were estimated. Results Compared with the lowest quintile of dietary nitrate intake (Q1;∼80 mg/day), the pooled MVRR for the highest quintile (Q5;∼240 mg/day) was 0.79 (95%CI, 0.66,0.93; p for trend [p-trend]=0.02). The dose-response was stronger (p for heterogeneity [p-het]=0.01) for POAG with early paracentral VF loss (433 cases; Q5 vs. Q1 MVRR=0.56; 95%CI, 0.40,0.79; p-trend=0.0003) than for POAG with peripheral VF loss only (835 cases; Q5 vs. Q1 MVRR=0.85; 95%CI, 0.68,1.06; p-trend=0.50). The association did not differ (p-het=0.75) by POAG subtypes defined by IOP (997 cases with IOP≥22 mm Hg: Q5 vs. Q1 MVRR=0.82; 95%CI, 0.67,1.01; p-trend=0.11 vs. 486 cases with IOP<22 mm Hg: Q5 vs. Q1 MVRR=0.71; 95%CI, 0.53,0.96; p-trend=0.12). Green leafy vegetables

  19. OPENING ANGLES OF COLLAPSAR JETS

    SciTech Connect

    Mizuta, Akira; Ioka, Kunihito

    2013-11-10

    We investigate the jet propagation and breakout from the stellar progenitor for gamma-ray burst (GRB) collapsars by performing two-dimensional relativistic hydrodynamic simulations and analytical modeling. We find that the jet opening angle is given by θ{sub j} ∼ 1/5Γ{sub 0} and infer the initial Lorentz factor of the jet at the central engine, Γ{sub 0}, is a few for existing observations of θ{sub j}. The jet keeps the Lorentz factor low inside the star by converging cylindrically via collimation shocks under the cocoon pressure and accelerates at jet breakout before the free expansion to a hollow-cone structure. In this new picture, the GRB duration is determined by the sound crossing time of the cocoon, after which the opening angle widens, reducing the apparent luminosity. Some bursts violating the maximum opening angle θ{sub j,{sub max}} ∼ 1/5 ∼ 12° imply the existence of a baryon-rich sheath or a long-acting jet. We can explain the slopes in both Amati and Yonetoku spectral relations using an off-centered photosphere model, if we make only one assumption that the total jet luminosity is proportional to the initial Lorentz factor of the jet. We also numerically calibrate the pre-breakout model (Bromberg et al.) for later use.

  20. Comparison of timolol 0.5% + brimonidine 0.2% + dorzolamide 2% versus timolol 0.5% + brimonidine 0.2% in a Mexican population with primary open-angle glaucoma or ocular hypertension

    PubMed Central

    Baiza-Durán, Leopoldo Martín; Llamas-Moreno, Juan Francisco; Ayala-Barajas, Clotilde

    2012-01-01

    Background The purpose of this study was to evaluate the efficacy and safety of two fixed combinations, ie, timolol 0.5% + brimonidine 0.2% + dorzolamide 2% (TBD) versus timolol 0.5% + brimonidine 0.2% (TB) in patients with primary open-angle glaucoma or ocular hypertension. Methods We performed a 3-month, randomized, double-blind study in patients with primary open-angle glaucoma or ocular hypertension and an intraocular pressure of 21–30 mmHg. Patients were randomly assigned to receive one drop of TBD or TB twice a day. The primary efficacy endpoint was change in intraocular pressure after 3 months of treatment. Safety measures were assessed by the presence of adverse events. Results Mean baseline intraocular pressure was similar at 8 am and 4 pm in the treatment groups (TBD 22.3 ± 0.9 mmHg, TB 22.4 ± 1.8 mmHg, P = 0.558; TBD 19.02 ± 1.3, TB 19.08 ± 1.2, P = 0.536, respectively). At the end of the study, the mean intraocular pressure was significantly lower in the TBD group at both 8 am (16.19 ± 2.0 mmHg versus 18.35 ± 1.4 mmHg, P = 0.000) and 4 pm (14.74 ± 2.4 mmHg versus 16.77 ± 1.4 mmHg, P = 0.000). Conclusion Fixed-combination TBD was more effective than fixed-combination TB for reducing IOP in patients with primary open-angle glaucoma. PMID:22848147

  1. Prospective unmasked randomized evaluation of the iStent inject® versus two ocular hypotensive agents in patients with primary open-angle glaucoma

    PubMed Central

    Fea, Antonio M; Belda, Jose I; Rękas, Marek; Jünemann, Anselm; Chang, Lydia; Pablo, Luis; Voskanyan, Lilit; Katz, L Jay

    2014-01-01

    Purpose The purpose of this study was to compare outcomes of subjects with open-angle glaucoma (OAG) not controlled on one medication who underwent either implantation of two iStent inject® trabecular micro-bypass devices or received medical therapy consisting of a fixed combination of latanoprost/timolol. Patients and methods Of 192 subjects who qualified for the study and were enrolled, 94 were randomized to surgery with implantation of two iStent inject® devices in the treated eye and 98 to receive medical therapy. Results At the month 12 visit, 94.7% of eyes (89/94) in the stent group reported an unmedicated intraocular pressure (IOP) reduction of ≥20% versus baseline unmedicated IOP, and 91.8% of eyes (88/98) in the medical therapy group reported an IOP reduction ≥20% versus baseline unmedicated IOP. A 17.5% between-group treatment difference in favor of the iStent inject group was statistically significant (P=0.02) at the ≥50% level of IOP reduction. An IOP ≤18 mmHg was reported in 92.6% of eyes (87/94) in the iStent inject group and 89.8% of eyes (88/98) in the medical therapy group. Mean (standard deviation) IOP decreases from screening of 8.1 (2.6) mmHg and 7.3 (2.2) mmHg were reported in the iStent inject and medical therapy groups, respectively. A high safety profile was also noted in this study in both the iStent inject and medical therapy groups, as measured by stable best corrected visual acuity, cup-to-disc ratio, and adverse events. Conclusion These data show that the use of iStent inject is at least as effective as two medications, with the clinical benefit of reducing medication burden and assuring continuous treatment with full compliance to implant therapy as well as having a highly favorable safety profile. PMID:24855336

  2. Ophthalmic and Glaucoma Treatment Characteristics Associated with Changes in Health-Related Quality of Life Before and After Newly Diagnosed Primary Open-Angle Glaucoma in Nurses Health Study Participants

    PubMed Central

    Bailey, Lucy A.; Okereke, Olivia I.; Kawachi, Ichiro; Cioffi, George A.; Pasquale, Louis R.; Kang, Jae H.

    2015-01-01

    Purpose To identify attributes related to glaucoma diagnosis or early glaucoma treatment patterns that are associated with changes in health-related quality of life among those with newly diagnosed primary open-angle glaucoma. Methods Among Nurses’ Health Study participants with incident medical record-confirmed primary open-angle glaucoma diagnosed in 1992–2000, we included 317 women who completed the Short-Form 36 Health Survey pre- and post-diagnosis. The two primary outcomes were 4-year changes (1992–1996 or 1996–2000) in the physical and mental component summary scores. Multiple regression models were used to estimate differences in score changes by early treatment pattern history and characteristics as of diagnosis (i.e., number of eyes affected, history of cataract, macular degeneration, cup-to-disc ratio, intraocular pressure, visual field loss type). Results In multivariable models, no ophthalmologic characteristics were associated with physical component score change. However, compared to treatment with eye drops or pills only, laser trabeculoplasty treatment (concomitant with history of treatment with eye drops or pills in 84%) was associated with a worse mental component score change over four years (-2.5 units; 95% confidence interval: −4.6, −0.3); this association was stronger with a family history of glaucoma (p-interaction=0.04) or with bilateral disease (p-interaction=0.001). Conclusions Among patients with incident glaucoma, no major factors were associated with change in physical well-being. However, compared to medical treatment only, a history of laser trabeculoplasty, which was commonly accompanied with a history of medical treatment and likely represented the need for a second line of treatment, was associated with a worse decline in mental well-being. PMID:26125994

  3. Comparison of the effects of bimatoprost and timolol on intraocular pressure and pulsatile ocular blood flow in patients with primary open-angle glaucoma: A prospective, open-label, randomized, two-arm, parallel-group study

    PubMed Central

    Vetrugno, Michele; Cardascia, Nicola; Cantatore, Francesco; Sborgia, Carlo

    2004-01-01

    Abstract Background: The current objective of antiglaucomatous therapy is to reduce intraocular pressure (IOP), and thus to preserve visual function. Many ophthalmologists believe this objective is best achieved by methods that improve ocular blood flow to the optic nerve head. Beta-blockers are effective ocular hypotensive agents, but they can reduce choroidal blood flow. Bimatoprost, a new prostamide analogue, has been shown to have a better IOP-lowering effect compared with the nonselective beta-adrenergic receptor blocker timolol maleate, but little is known about its effects on the vascular bed of the eye. Objective: The aim of this study was to compare the effects of bimatoprost and timolol on IOP and choroidal blood flow (as measured using pulsatile ocular blood flow [pOBF]) in patients with primary open-angle glaucoma (POAG). Methods: This prospective, open-label, randomized, 2-arm, parallel-group study was conducted at the Glaucoma Research Centre, Department of Ophthalmology, University Hospital of Bari, Bari, Italy. Patients with POAG having well-controlled IOP (<16 mm Hg) on monotherapy with timolol 0.5% ophthalmic solution (2 drops per affected eye BID) for ≥12 months but with a progressive decrease in pOBF during the same time period were randomly allocated to 1 of 2 treatment groups. One group continued monotherapy with timolol, 2 drops per affected eye BID. The other group was switched (without washout) to bimatoprost 0.3% ophthalmic solution (2 drops per affected eye QD [9 pm]). Treatment was given for 180 days. IOP and pOBF were assessed at the diagnostic visit (pre-timolol), baseline (day 0), and treatment days 15, 30, 60, 90, and 180. Primary adverse effects (AEs) (ie, conjunctival hyperemia, conjunctival papillae, stinging, burning, foreign body sensation, and pigmentation of periorbital skin) were monitored throughout the study. Results: Thirty-eight patients were enrolled (22 men, 16 women; mean [SD] age, 51.7 [4.8] years; 19 patients per

  4. Safety and Efficacy of Two Trabecular Micro-Bypass Stents as the Sole Procedure in Japanese Patients with Medically Uncontrolled Primary Open-Angle Glaucoma: A Pilot Case Series

    PubMed Central

    Hosoda, Shingo; Yaguchi, Saori

    2017-01-01

    Purpose. To evaluate efficacy and safety of a trabecular micro-bypass stent system when used as the sole procedure in Japanese patients with medically uncontrolled primary open-angle glaucoma (POAG). Design. Prospective nonrandomized interventional pilot study. Methods. Ten eyes of 10 Japanese patients with medically uncontrolled POAG taking three ocular hypotensive medications were treated using only the implantation of two iStent trabecular micro-bypass stents. Each patient continued to take the same ocular hypotensive medications used preoperatively throughout the study. Intraocular pressure (IOP) and endothelial cell density (ECD) were determined at baseline and at 1, 3, and 6 months postoperatively. Best-corrected visual acuity (BCVA) was measured at baseline and 6 months after surgery. Results. Mean IOP was 22.0 ± 3.0 mmHg at baseline and 16.9 ± 3.6 mmHg at 6 months, which represented a mean reduction of 5.1 mmHg or 23.2%. No significant changes were observed in the ECD and BCVA. Complications that occurred during the early postoperative period included hyphema, peripheral anterior synechiae, and occlusion of the stent by the iris. Conclusion. Implantation of two trabecular micro-bypass stents as the sole procedure in Japanese POAG patients effectively reduced IOP and exhibited a favorable safety profile. Clinical Trials Registration number is UMIN000004002. PMID:28265466

  5. Size of the Optic Nerve Head and Its Relationship with the Thickness of the Macular Ganglion Cell Complex and Peripapillary Retinal Nerve Fiber Layer in Patients with Primary Open Angle Glaucoma

    PubMed Central

    Enomoto, Nobuko; Anraku, Ayako; Ishida, Kyoko; Takeyama, Asuka; Yagi, Fumihiko; Tomita, Goji

    2015-01-01

    Purpose. To evaluate the relationships among the optic nerve head (ONH) area, macular ganglion cell complex (mGCC) thickness, circumpapillary retinal nerve fiber layer (cpRNFL) thickness, and visual field defects in patients with primary open angle glaucoma (POAG). Methods. This retrospective study included 90 eyes of 90 patients with POAG. The ONH area, rim area, mGCC thickness, and cpRNFL thickness were measured using optical coherence tomography. Mean deviation (MD) was measured using standard automated perimetry. The relationships among clinical factors including age, refraction, the ONH area, the rim area, the mGCC thickness, the cpRNFL thickness, and MD were evaluated using correlation coefficients and multiple regression analyses. Results. The significant correlation of the ONH area with refraction (r = 0.362, P < 0.001), the mGCC thickness (r = 0.225, P = 0.033), and the cpRNFL thickness (r = 0.253, P = 0.016) was found. Multiple regression analysis showed that the ONH area, rim area, and MD were selected as significant contributing factors to explain the mGCC thickness and cpRNFL thickness. No factor was selected to explain MD. Conclusions. The ONH area, in other words, the disc size itself may affect the mGCC thickness and cpRNFL thickness in POAG patients. PMID:26339503

  6. A comparison of the sensitivity of EQ-5D, SF-6D and TTO utility values to changes in vision and perceived visual function in patients with primary open-angle glaucoma

    PubMed Central

    2012-01-01

    Background Economic viability of treatments for primary open-angle glaucoma (POAG) should be assessed objectively to prioritise health care interventions. This study aims to identify the methods for eliciting utility values (UVs) most sensitive to differences in visual field and visual functioning in patients with POAG. As a secondary objective, the dimensions of generic health-related and vision-related quality of life most affected by progressive vision loss will be identified. Methods A total of 132 POAG patients were recruited. Three sets of utility values (EuroQoL EQ-5D, Short Form SF-6D, Time Trade Off) and a measure of perceived visual functioning from the National Eye Institute Visual Function Questionnaire (VFQ-25) were elicited during face-to-face interviews. The sensitivity of UVs to differences in the binocular visual field, visual acuity and visual functioning measures was analysed using non-parametric statistical methods. Results Median utilities were similar across Integrated Visual Field score quartiles for EQ-5D (P = 0.08) whereas SF-6D and Time-Trade-Off UVs significantly decreased (p = 0.01 and p = 0.001, respectively). The VFQ-25 score varied across Integrated Visual Field and binocular visual acuity groups and was associated with all three UVs (P ≤ 0.001); most of its vision-specific sub-scales were associated with the vision markers. The most affected dimension was driving. A relationship with vision markers was found for the physical component of SF-36 and not for any dimension of EQ-5D. Conclusions The Time-Trade-Off was more sensitive than EQ-5D and SF-6D to changes in vision and visual functioning associated with glaucoma progression but could not measure quality of life changes in the mildest disease stages. PMID:22909264

  7. Positional and Curvature Difference of Lamina Cribrosa According to the Baseline Intraocular Pressure in Primary Open-Angle Glaucoma: A Swept-Source Optical Coherence Tomography (SS-OCT) Study

    PubMed Central

    Kim, Yong Woo; Jeoung, Jin Wook; Girard, Michael J. A.; Mari, Jean Martial; Park, Ki Ho

    2016-01-01

    Purpose To investigate the variation of lamina cribrosa (LC) structure based on the baseline intraocular pressure (IOP) in eyes with primary open-angle glaucoma (POAG) and healthy individuals using swept-source optical coherence tomography. Methods A total of 108 eyes with POAG and 61 healthy eyes were recruited. Based on the baseline IOP, the POAG eyes were divided into higher-baseline IOP (HTG; baseline IOP > 21 mmHg, n = 38 eyes) and lower-baseline IOP (NTG; baseline IOP ≤ 21 mmHg, n = 70 eyes). The anterior laminar insertion depth (ALID), mean LC depth (mLCD), and the LC curvature index (mLCD–ALID) were measured, and compared among the three groups. The regional variation of LC structure was evaluated by vertical-horizontal ALID difference. Results The mLCD and LC curvature index were greatest in HTG eyes (520.3 ± 123.0 and 80.9 ± 30.7 μm), followed by NTG (463.2 ± 110.5 and 64.5 ± 30.7 μm) and healthy eyes (382.9 ± 107.6 and 47.6 ± 25.7 μm, all P < 0.001). However, there were no significant difference in ALID between HTG and NTG eyes. The vertical-horizontal ALID difference was larger in NTG eyes (72.8 ± 56.2 μm) than in HTG (32.7 ± 61.4 μm, P = 0.004) and healthy eyes (25.5 ± 34.8 μm, P < 0.001). Conclusions Lamina cribrosa position and curvature differed in POAG eyes with low and high IOP. This would support the theory that IOP induced biomechanical effects on the optic play a role on glaucoma. PMID:27611970

  8. A Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of 2 and 4 Weeks of Twice-Daily Ocular Trabodenoson in Adults with Ocular Hypertension or Primary Open-Angle Glaucoma

    PubMed Central

    Sall, Kenneth N.; DuBiner, Harvey; Slomowitz, Natanya; McVicar, William; Rich, Cadmus C.; Baumgartner, Rudolf A.

    2016-01-01

    Abstract Purpose: To evaluate the safety and ocular hypotensive efficacy of 4 trabodenoson doses administered twice daily over 14 or 28 days in subjects with ocular hypertension or primary open-angle glaucoma (POAG). Methods: In this multicenter, randomized, double-masked, placebo-controlled, dose-escalation Phase 2 study, patients received unilateral topical twice-daily trabodenoson (50, 100, or 200 mcg) or placebo for 14 days, or 500 mcg trabodenoson or placebo for 28 days. Ocular and systemic safety and tolerability were assessed by examinations, clinical and laboratory studies. Intraocular pressure (IOP) was assessed using Goldmann tonometry. Results: Trabodenoson was well tolerated; no clinically meaningful ocular or systemic side effects were identified. Trabodenoson produced a dose-dependent IOP reduction. IOP reductions in the 500 mcg group were significantly greater than placebo at all time points at Day 28. Mean IOP reductions from diurnal baseline ranged from −3.5 to −5.0 mmHg with a mean change of −4.1 mmHg in the 500 mcg group compared −1.0 to −2.5 mmHg with a mean change of −1.6 mmHg for the placebo group, and the Day 28 drop was significantly greater than at Day 14 (P = 0.0163) indicating improvement in IOP lowering with longer treatment time. IOP remained significantly reduced 24 h after the final 500 mcg dose (P = 0.048). Conclusion: Twice-daily ocular doses of trabodenoson, from 50 to 500 mcg, were well tolerated and showed a dose-related decrease in IOP that was statistically significant and clinically relevant at 500 mcg in patients with ocular hypertension or POAG. PMID:27002298

  9. Efficacy and Tolerability of Travoprost 0.004%/Timolol 0.5% Fixed-Dose Combination for the Treatment of Primary Open-Angle Glaucoma or Ocular Hypertension Inadequately Controlled with Beta-Blocker Monotherapy

    PubMed Central

    Park, Ki Ho; Hubatsch, Douglas A.; Erichev, Valeriy; Paczka, Jose A.; Roberts, Timothy V.

    2017-01-01

    Objective. To evaluate the efficacy and tolerability of travoprost 0.004%/timolol 0.5% fixed-dose combination (TTFC) in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT) inadequately controlled on beta-blocker monotherapy. Methods. In this phase IV, open-label study, 156 patients on beta-blocker monotherapy with mean intraocular pressure (IOP) between 18 and 32 mmHg were randomized (no washout period) to receive TTFC for 8 weeks (TTFC group) or to continue beta-blocker monotherapy for 4 weeks followed by TTFC for the remaining 4 weeks (beta-blocker group). Results. The mean IOP (±standard deviation) at baseline in the TTFC and beta-blocker groups was 22.5 ± 2.5 mmHg and 22.2 ± 2.3 mmHg, respectively, and at weeks 4 and 8, was 16.7 ± 3.1 mmHg and 16.1 ± 3.1 mmHg, respectively, in TTFC group and 21.1 ± 3.1 mmHg and 16.1 ± 2.8 mmHg, respectively, in the beta-blocker group. There was a significant least squares mean difference between TTFC and beta-blocker in 8 a.m. IOP at week 4 (−4.6 mmHg; one-sided 95% confidence interval [−inf, −3.9]; p < 0.0001 [primary endpoint]); the upper bound of the 95% confidence interval was within the prespecified limit (<0). Both treatments were well tolerated. Conclusion. Superior IOP control was achieved with TTFC in patients with OAG or OHT previously uncontrolled with beta-blockers. No new safety findings were identified. This trial is registered with ClinicalTrials.gov NCT02003391. PMID:28239491

  10. Efficacy and Tolerability of Travoprost 0.004%/Timolol 0.5% Fixed-Dose Combination for the Treatment of Primary Open-Angle Glaucoma or Ocular Hypertension Inadequately Controlled with Beta-Blocker Monotherapy.

    PubMed

    Lerner, Simon Fabian; Park, Ki Ho; Hubatsch, Douglas A; Erichev, Valeriy; Paczka, Jose A; Roberts, Timothy V

    2017-01-01

    Objective. To evaluate the efficacy and tolerability of travoprost 0.004%/timolol 0.5% fixed-dose combination (TTFC) in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT) inadequately controlled on beta-blocker monotherapy. Methods. In this phase IV, open-label study, 156 patients on beta-blocker monotherapy with mean intraocular pressure (IOP) between 18 and 32 mmHg were randomized (no washout period) to receive TTFC for 8 weeks (TTFC group) or to continue beta-blocker monotherapy for 4 weeks followed by TTFC for the remaining 4 weeks (beta-blocker group). Results. The mean IOP (±standard deviation) at baseline in the TTFC and beta-blocker groups was 22.5 ± 2.5 mmHg and 22.2 ± 2.3 mmHg, respectively, and at weeks 4 and 8, was 16.7 ± 3.1 mmHg and 16.1 ± 3.1 mmHg, respectively, in TTFC group and 21.1 ± 3.1 mmHg and 16.1 ± 2.8 mmHg, respectively, in the beta-blocker group. There was a significant least squares mean difference between TTFC and beta-blocker in 8 a.m. IOP at week 4 (-4.6 mmHg; one-sided 95% confidence interval [-inf, -3.9]; p < 0.0001 [primary endpoint]); the upper bound of the 95% confidence interval was within the prespecified limit (<0). Both treatments were well tolerated. Conclusion. Superior IOP control was achieved with TTFC in patients with OAG or OHT previously uncontrolled with beta-blockers. No new safety findings were identified. This trial is registered with ClinicalTrials.gov NCT02003391.

  11. Role of CYP1B1, MYOC, OPTN and OPTC genes in adult-onset primary open-angle glaucoma: predominance of CYP1B1 mutations in Indian patients

    PubMed Central

    Basavaraj, Manjunath G.; Gupta, Santosh K.; Qamar, Imteyaz; Ali, Abdullah Mahmood; Bajaj, Vineeta; Ramesh, T.K.; Prakash, D. Ravi; Shetty, Jyoti S.; Dorairaj, Syril K.

    2007-01-01

    Purpose Mutations in the CYP1B1, MYOC, OPTN, and WDR36 genes result in glaucoma. Given its expression in the optic nerve, it is likely a mutation in the OPTC gene is also involved in initiating glaucoma. This study was designed to evaluate the involvement of the CYP1B1, MYOC, OPTN, and OPTC genes in the etiology of adult-onset primary open-angle glaucoma (POAG) found in 251 Indian patients. Methods Blood samples were obtained from individuals for DNA isolation. A combination of polymerase chain reaction-single strand conformation polymorphism, allele-specific PCR, and DNA sequencing techniques were used to detect mutations in four genes. Four microsatellite markers from the CYP1B1 candidate region and three intragenic CYP1B1 single nucleotide polymorphisms (SNPs) were used to determine the origin of the most common CYP1B1 mutations. Results Three previously known mutations (Pro193Leu, Glu229Lys, and Arg368His) and one novel (Met292Lys) mutation were found in the CYP1B1 gene. Frequencies of the most common mutations, Glu229Lys and Arg368His, in patients were 5.12% and 3.98%, respectively. The Glu229Lys and Arg368His mutations were also found in normal controls at frequencies of 5% and 2%, respectively, suggesting that these mutations might be polymorphic variants in our population. The absence of allele sharing for D2S177, D2S1346, D2S2974, and D2S2331 markers and three intragenic CYP1B1 SNPs in patients suggested multiple origins for the Glu229Lys and Arg368His variants. Two of 251 (0.8%) patients had the Gln48His mutation in MYOC. There was no difference in the frequency of a MYOC -83G>A promoter polymorphism between patients and controls. A novel OPTN mutation, Thr202Arg, was detected in one of 251 (0.4%) patients. The OPTN variant Met98Lys was detected in similar frequencies in patients and controls. No mutation was detected in OPTC. Taken together, 3.59% (9/251) of our POAG patients had mutations in the CYP1B1, MYOC, and OPTN genes. Conclusions This is the

  12. Novel therapies for open-angle glaucoma

    PubMed Central

    Wentz, Scott M.; Kim, Nathaniel J.; Wang, Jenny; Amireskandari, Annahita; Siesky, Brent

    2014-01-01

    Open-angle glaucoma is a multifactorial optic neuropathy characterized by progressive loss of retinal ganglion cells and their axons. It is an irreversible disease with no established cure. The only currently approved treatment is aimed at lowering intraocular pressure, the most significant risk factor known to date. However, it is now clear that there are other risk factors involved in glaucoma's pathophysiology. To achieve future improvements in glaucoma management, new approaches to therapies and novel targets must be developed. Such therapies may include new tissue targets for lowering intraocular pressure, molecules influencing ocular hemodynamics, and treatments providing neuroprotection of retinal ganglion cells. Furthermore, novel drug delivery systems are in development that may improve patient compliance, increase bioavailability, and decrease adverse side effects. PMID:25580256

  13. Identification of a novel MYOC mutation, p.(Trp373), in a family with open angle glaucoma.

    PubMed

    Crawford, April; Souzeau, Emmanuelle; Agar, Ashish; Ridge, Bronwyn; Dubowsky, Andrew; Burdon, Kathryn P; Craig, Jamie E

    2014-07-25

    MYOC gene variants are associated with autosomal dominant primary open angle glaucoma (POAG). In this study, we describe a previously unreported MYOC variant segregating with a POAG phenotype in an Australian family. Two individuals affected with POAG and three unaffected individuals from the same family were recruited through the Australian and New Zealand Registry of Advanced Glaucoma (ANZRAG). Direct sequencing of all MYOC coding exons identified the novel heterozygous single nucleotide transition MYOC:c.1119G>A, p.(Trp373), predicted to encode an aberrant truncated MYOC protein in two affected siblings. Two unaffected siblings and an unaffected niece were negative for the MYOC sequence variant.

  14. Large optical field enhancement for nanotips with large opening angles

    NASA Astrophysics Data System (ADS)

    Thomas, Sebastian; Wachter, Georg; Lemell, Christoph; Burgdörfer, Joachim; Hommelhoff, Peter

    2015-06-01

    We theoretically investigate the dependence of the enhancement of optical near-fields at nanometric tips on the shape, size, and material of the tip. We confirm the strong dependence of the field enhancement factor on the radius of curvature. In addition, we find a surprisingly strong increase of field enhancement with increasing opening angle of the nanotips. For gold and tungsten nanotips in the experimentally relevant parameter range (radius of curvature ≥slant 5 nm at 800 nm laser wavelength), we obtain field enhancement factors of up to ∼ 35 for Au and ∼ 12 for W for large opening angles. We confirm this strong dependence on the opening angle for many other materials featuring a wide variety in their dielectric response. For dielectrics, the opening angle dependence is traced back to the electrostatic force of the induced surface charge at the tip shank. For metals, the plasmonic response strongly increases the field enhancement and shifts the maximum field enhancement to smaller opening angles.

  15. Clinical results of Trabectome surgery for open-angle glaucoma

    PubMed Central

    Mizoguchi, Takanori; Nishigaki, Shiro; Sato, Tomoki; Wakiyama, Harumi; Ogino, Nobuchika

    2015-01-01

    Background The purpose of this study was to determine outcomes when using Trabectome surgery and to evaluate factors associated with its effects in primary open-angle glaucoma (POAG) and exfoliation glaucoma (EXG). Methods This was a prospective, non-randomized, observational, comparative cohort study in which Trabectome surgery was used alone in patients with POAG or EXG. Trabectome surgery was considered to have failed when at least one of the following three criteria was fulfilled: intraocular pressure (IOP) ≥21 mmHg and a <20% reduction below the baseline IOP on two consecutive follow-up visits 3 months or more after surgery; need for additional glaucoma surgery; and an increase in number of medications compared with baseline. Results The subjects were 32 males (34 eyes) and 46 females (48 eyes). POAG was observed in 43 eyes and EXG in 39 eyes. IOP after Trabectome surgery decreased significantly from 22.3±6.8 mmHg at baseline to 14.0±3.9 mmHg (23.0% reduction) at month 24 in all cases (P<0.0000). The success rate at 2 years was 51.2% for all cases (POAG, 50.9%; EXG, 49.2%). There was no significant difference in success rate between POAG and EXG (P=0.91). Preoperative IOP (P=0.033) and number of medications (P=0.041) were significant factors for surgical success/failure in multivariate logistic regression. No serious complications were observed. Conclusion Trabectome surgery achieved favorable IOP control and was equally effective in patients with POAG and those with EXG. Its effects were influenced by preoperative IOP and number of preoperative medications. PMID:26487799

  16. New drugs and preparations for open-angle glaucoma in adults.

    PubMed

    2015-12-01

    Primary (or chronic) open-angle glaucoma (POAG or COAG) may be asymptomatic but causes progressive optic nerve damage with significant loss of visual field. Treatments aim to lower intraocular pressure (IOP) by reducing the production of aqueous humour and/or increasing its drainage. Here we update our previous articles to reflect new drugs, preservative-free preparations and fixed-dose drug combinations for POAG.

  17. Efficacy and Safety of Trabectome Surgery in Chinese Open-Angle Glaucoma

    PubMed Central

    Lee, Jacky W.Y.; Yick, Doris W.F.; Tsang, Susanna; Yuen, Can Y.F.; Lai, Jimmy S.M.

    2016-01-01

    Abstract To investigate the clinical outcome of the Trabectome in Chinese open-angle glaucoma (OAG). This prospective case series recruited pseudophakic glaucoma subjects with open-angle configuration. Trabeculectomy ab interno was performed using the Trabectome to 120° of the trabecular meshwork. Intraocular pressure (IOP) and medications were recorded preoperatively and every 3 months postoperatively. Visual acuity was measured preoperatively and at 1 and 6 months postoperatively. One-way ANOVA with Tukey Multiple Comparison Test were used to measure the pre and postoperative parameters. In 19 eyes of 19 Chinese subjects, 26.3% were uveitic, 68.4% were primary open-angle glaucoma, and 5.3% had a history of chronic angle-closure glaucoma with open-angles after cataract extraction. The subjects’ mean age was 67.5 ± 14.4 years, with 4 females and 15 males. Two patients required secondary filtration procedure. At 6 months, the IOP reduced by 34.8% (24.4 ± 4.4 mm Hg to 15.9 ± 5.1 mm Hg, P < 0.0001). The number of types of antiglaucoma medications was reduced by 28.2% (3.9 ± 0.8–2.8 ± 1.6, P < 0.0001). The visual acuity was static at 1 and 6 months postoperatively (P = 0.4). There were no intraoperative complications. 26.3% of subjects had a transient IOP spike > 21 mm Hg, 1 had hyphema requiring washout, and 1 had reactivation of herpetic keratitis. The success rate at 6 months was 89.5%. Trabectome achieved a modest reduction in IOP and medications in the majority of pseudophakic Chinese OAG eyes. PMID:27082559

  18. Association between choroidal thickness and anterior chamber segment in eyes with narrow or open-angle

    PubMed Central

    Li, Song-Feng; Wu, Ge-Wei; Chen, Chang-Xi; Shen, Ling; Zhang, Zhi-Bao; Gao, Fei; Wang, Ning-Li

    2016-01-01

    AIM To investigate the relationship between choroidal thickness and anterior chamber segment in subjects with eyes with narrow or open-angle. METHODS The subfoveal choroidal thickness was measured with enhanced depth-imaging optical coherence tomography and anterior chamber parameters were measured with ultrasound biomicroscopy in one eye of 23 subjects with open-angle eyes and 38 subjects with narrow-angle eyes. The mean age was 59.52±7.04y for narrow-angle subjects and 60.76±7.23y for open-angle subjects (P=0.514). Multivariate linear regression analysis was performed to assess the association between choroidal thickness and narrow-angle parameters. RESULTS There were no differences in subfoveal choroidal thickness between open- and narrow-angle subjects (P=0.231). Anterior chamber parameters, including central anterior chamber depth, trabecular iris angle, iris thickness 500 µm from the scleral spur (IT500), and ciliary body thickness at 1 mm and 2 mm from the scleral spur (CBT1, CBT2) showed significant differences between the two groups (P<0.05). Subfoveal choroidal thickness showed negative correlation (β=-0.496, P=0.016) only with anterior chamber depth in the open-angle group and with age (β=-0.442, P=0.003) and IT500 (β=-0.399, P=0.008) in the narrow-angle group. However, subfoveal choroidal thickness was not correlated with trabecular iris angle, anterior chamber depth, ciliary body thickness, or central corneal thickness in the narrow-angle group. CONCLUSION Choroidal thickness does not differ in the two groups and has not correlated with anterior chamber parameters in narrow-angle subjects, suggesting a lack of relationship between choroidal thickness and primary angle-closure glaucoma. PMID:27588269

  19. Advanced textile applications for primary aircraft structures

    NASA Technical Reports Server (NTRS)

    Jackson, Anthony C.; Barrie, Ronald E.; Shah, Bharat M.; Shukla, Jay G.

    1992-01-01

    Advanced composite primary structural concepts were evaluated for low cost, damage tolerant structures. Development of advanced textile preforms for fuselage structural applications with resin transfer molding and powder epoxy materials are now under development.

  20. Advanced textile applications for primary aircraft structures

    NASA Technical Reports Server (NTRS)

    Jackson, Anthony C.; Barrie, Ronald E.; Shah, Bharat M.; Shukla, Jay G.

    1992-01-01

    Advanced composite primary structural concepts have been evaluated for low cost, damage tolerant structures. Development of advanced textile preforms for fuselage structural applications with resin transfer molding and powder epoxy material is now under development.

  1. PULSAR BINARY BIRTHRATES WITH SPIN-OPENING ANGLE CORRELATIONS

    SciTech Connect

    O'Shaughnessy, Richard; Kim, Chunglee E-mail: ckim@astro.lu.s

    2010-05-20

    One ingredient in an empirical birthrate estimate for pulsar binaries is the fraction of sky subtended by the pulsar beam: the pulsar beaming fraction. This fraction depends on both the pulsar's opening angle and the misalignment angle between its spin and magnetic axes. The current estimates for pulsar binary birthrates are based on an average value of beaming fractions for only two pulsars, i.e., PSRs B1913+16 and B1534+12. In this paper, we revisit the observed pulsar binaries to examine the sensitivity of birthrate predictions to different assumptions regarding opening angle and alignment. Based on empirical estimates for the relative likelihood of different beam half-opening angles and misalignment angles between the pulsar rotation and magnetic axes, we calculate an effective beaming correction factor, f{sub b,eff}, whose reciprocal is equivalent to the average fraction of all randomly selected pulsars that point toward us. For those pulsars without any direct beam geometry constraints, we find that f{sub b,eff} is likely to be smaller than 6, a canonically adopted value when calculating birthrates of Galactic pulsar binaries. We calculate f{sub b,eff} for PSRs J0737-3039A and J1141-6545, applying the currently available constraints for their beam geometry. As in previous estimates of the posterior probability density function P(R) for pulsar binary birthrates R, PSRs J0737-3039A and J1141-6545 still significantly contribute to, if not dominate, the Galactic birthrate of tight pulsar-neutron star (NS) and pulsar-white dwarf (WD) binaries, respectively. Our median posterior present-day birthrate predictions for tight PSR-NS binaries, wide PSR-NS binaries, and tight PSR-WD binaries given a preferred pulsar population model and beaming geometry are 89 Myr{sup -1}, 0.5 Myr{sup -1}, and 34 Myr{sup -1}, respectively. For long-lived PSR-NS binaries, these estimates include a weak (x1.6) correction for slowly decaying star formation in the galactic disk. For pulsars

  2. Optical layouts for large infrared beamline opening angles

    NASA Astrophysics Data System (ADS)

    Moreno, Th; Westfahl, H.; de Oliveira Freitas, R.; Petroff, Y.; Dumas, P.

    2013-03-01

    The number of infrared beamlines at synchrotron facilities is expending worldwide. Due to the long wavelength of the radiation in the infrared region, the optimum collection of the emitted photons requires large opening angles, both vertically and horizontally (order of few tens of mrad). Most of the infrared beamlines use toroid shaped mirrors, or elliptical mirror to conjointly focus both the vertical and the horizontal source emission. However, such optical set ups produce distorted images due to the optical aberrations produced by the depth and the circular shape of the source. In this article, we propose a new optical layout consisting in two optimized shape mirrors, focusing independently the vertical and the horizontal source emission, and providing low aberration beams for large horizontal apertures. The setup has been used to design the new LNLS Brazilian synchrotron Infrared beamline.

  3. Cosmic Ray Energy Determination by the Reduced-Opening Angle Method

    NASA Technical Reports Server (NTRS)

    Smith, Arthur E.; Gregory, John C.

    1998-01-01

    Accurate measurement of the primary galactic cosmic ray species energy dependence in the regime beyond approx. 500 GeV/a is difficult due to the low flux and the limitations of energy measurement techniques. However, such observations are essential to resolve several questions of current interest such as: Is the enrichment of heavy species (Z greater that or equal to 6) cosmic rays first reported at higher energies by the proton satellite' and then later at lower energies real? The results from a previous deployment of the reduced opening angle technique are inconclusive but the authors do point to limitations in the previous techniques. Another intriguing puzzle is the energy dependence of silicon cosmic rays. Two independent experiments using different experimental techniques indicate that silicon is under-abundant. At present the observation is limited by statistics; it could still be a three sigma fluctuation. However, if confirmed the current models of acceleration and propagation which are species independent are seriously inadequate. To progress further the species and energy dependence must be accurately measured in a manner that is free from systematic uncertainty. In this report we show that the reduced opening angle method offers a simple and relatively inexpensive method to answer these questions. First we present the physics of the reduced opening angle and indicate the expected energy and charge resolution. The proposed detector design is then presented followed by the expected performance. Where ever possible simple phenomenological expressions that allow 'back of the envelope' estimates are given. More details are presented in the appendices. The limit of the energy resolution and the expected event rates for iron cosmic rays are calculated. Salient points are summarized in the conclusions.

  4. A comparison of betaxolol and timolol in open angle glaucoma and ocular hypertension.

    PubMed

    Feghali, J G; Kaufman, P L; Radius, R L; Mandell, A I

    1988-04-01

    In a randomized, double-masked study, 41 patients with primary open-angle glaucoma or ocular hypertension were treated with betaxolol 0.5% or timolol 0.5% drops for 26 weeks. The average decrease in intraocular pressure (IOP) over the total study period was significant with both betaxolol (-6.3 mmHg) and timolol (-7.2 mmHg) in patients receiving no adjunctive therapy. There was no difference between betaxolol and timolol with respect to changes from baseline IOP. Significantly decreased mean brachial arterial pressure (MAP) was seen only with timolol, although the difference between the two groups was not significant. Pulse, pupil size, and basal tear secretion were unchanged in both groups. Burning upon instillation of the drops was more frequent with betaxolol.

  5. On the evolution of jet energy and opening angle in strongly coupled plasma

    NASA Astrophysics Data System (ADS)

    Chesler, Paul M.; Rajagopal, Krishna

    2016-05-01

    We calculate how the energy and the opening angle of jets in {N} = 4 SYM theory evolve as they propagate through the strongly coupled plasma of that theory. We define the rate of energy loss dE jet /dx and the jet opening angle in a straightforward fashion directly in the gauge theory before calculating both holographically, in the dual gravitational description. In this way, we rederive the previously known result for dE jet /dx without the need to introduce a finite slab of plasma. We obtain a striking relationship between the initial opening angle of the jet, which is to say the opening angle that it would have had if it had found itself in vacuum instead of in plasma, and the thermalization distance of the jet. Via this relationship, we show that {N} = 4 SYM jets with any initial energy that have the same initial opening angle and the same trajectory through the plasma experience the same fractional energy loss. We also provide an expansion that describes how the opening angle of the {N} = 4 SYM jets increases slowly as they lose energy, over the fraction of their lifetime when their fractional energy loss is not yet large. We close by looking ahead toward potential qualitative lessons from our results for QCD jets produced in heavy collisions and propagating through quark-gluon plasma.

  6. On the evolution of jet energy and opening angle in strongly coupled plasma

    SciTech Connect

    Chesler, Paul M.; Rajagopal, Krishna

    2016-05-17

    We calculate how the energy and the opening angle of jets in N = 4SYM theory evolve as they propagate through the strongly coupled plasma of that theory. We define the rate of energy loss dEjet/dx and the jet opening angle in a straightforward fashion directly in the gauge theory before calculating both holographically, in the dual gravitational description. In this way, we rederive the previously known result for dEjet/dx without the need to introduce a finite slab of plasma. We obtain a striking relationship between the initial opening angle of the jet, which is to say the opening angle that it would have had if it had found itself in vacuum instead of in plasma, and the thermalization distance of the jet. Via this relationship, we show that N = 4SYM jets with any initial energy that have the same initial opening angle and the same trajectory through the plasma experience the same fractional energy loss. We also provide an expansion that describes how the opening angle of the N = 4SYM jets increases slowly as they lose energy, over the fraction of their lifetime when their fractional energy loss is not yet large. In conclusion, we close by looking ahead toward potential qualitative lessons from our results for QCD jets produced in heavy collisions and propagating through quark-gluon plasma.

  7. Advances of gene therapy for primary immunodeficiencies

    PubMed Central

    Candotti, Fabio

    2016-01-01

    In the recent past, the gene therapy field has witnessed a remarkable series of successes, many of which have involved primary immunodeficiency diseases, such as X-linked severe combined immunodeficiency, adenosine deaminase deficiency, chronic granulomatous disease, and Wiskott-Aldrich syndrome. While such progress has widened the choice of therapeutic options in some specific cases of primary immunodeficiency, much remains to be done to extend the geographical availability of such an advanced approach and to increase the number of diseases that can be targeted. At the same time, emerging technologies are stimulating intensive investigations that may lead to the application of precise genetic editing as the next form of gene therapy for these and other human genetic diseases. PMID:27508076

  8. Fascicular Visual Field Defects in Open-Angle Glaucoma: Evaluation with Microperimetry

    PubMed Central

    Fratipietro, Manuela; Malagola, Romualdo

    2016-01-01

    Purpose. Use of microperimetry (Mp-1), correlating with Humphrey perimetry (30-2 program), in patients affected by primary open-angle glaucoma (POAG) with perimetric defects, in order to obtain an evaluation of the accuracy of the results obtained by Mp-1. Materials and Methods. In this study 40 eyes of 25 patients affected by POAG with perimetric defects were included. All patients underwent microperimetry test by Nidek Mp-1 (NAVIS software version 1.7.2, Nidek Technologies). Mean sensitivity values expressed in decibel (dB) of all tested dots and mean values for each quadrant obtained by microperimetric test were correlated with corresponding quadrants obtained by static perimetry analysis. Data were analyzed by Pearson's correlation and Bland-Altman analysis. Results. Interpolated data showed that mean sensitivity values in all spots tested by Mp-1 (11.98 dB, SD 4.31) may be significantly correlated with mean total values obtained by Humphrey 30-2 perimetry (17.95, SD 4.32), with correlation coefficient of 0.556. Conclusions. Topographic visualization of the perimetric alteration by microperimetry allows retesting areas with reduced sensitivity which are topographically visualized and displayable on the ocular fundus examination, avoiding worsening of the functional defect by better modulation of the antiglaucoma therapy and therefore it allows better monitoring of the pathologic functional damage. PMID:27366329

  9. Comparison of canaloplasty and trabeculectomy for open angle glaucoma: a Meta-analysis

    PubMed Central

    Lin, Zhong-Jing; Xu, Shuo; Huang, Shou-Yue; Zhang, Xiao-Bin; Zhong, Yi-Sheng

    2016-01-01

    AIM To evaluate the advantage of canaloplasty compared to trabeculectomy for patients with open angle glaucoma. METHODS Potentially relevant studies were systematically searched using various databases from inception until December 2015. The outcome analyses performed automatically using Revman 5.3 included intraocular pressure reduction (IOPR), postoperative success rate, anti-glaucoma medications reduction and the incidence of adverse events. RESULTS We included four qualified studies incorporating a total of 215 eyes for quantitative synthesis. The weighted mean difference (WMD) of IOPR between canaloplasty and trabeculectomy from baseline to 12mo was -2.33 (95%CI: -4.00, -0.66). There was not significant improvement in the complete or qualified success rate (OR: 0.58, 95%CI: 0.26, 1.31; OR: 0.50, 95%CI: 0.10, 2.44, respectively). Similarly, no statistically significance was observed in anti-glaucoma mediations reduction (WMD: -0.54, 95%CI: -1.18, 0.09). Sensitivity analysis of the primary outcome estimate confirmed the stability of the Meta-analysis result. CONCLUSION Trabeculectomy seems to be more effective in lowering IOP up to 12mo when comparing with canaloplasty. Canaloplasty does not seem to be inferior to trabeculectomy considering the postoperative success rate or the number of postoperative anti-glaucoma medications. Meanwhile, it has an advantage of less bleb related complications. PMID:28003985

  10. Lens Position Parameters as Predictors of Intraocular Pressure Reduction After Cataract Surgery in Nonglaucomatous Patients With Open Angles

    PubMed Central

    Hsu, Chi-Hsin; Kakigi, Caitlin L.; Lin, Shuai-Chun; Wang, Yuan-Hung; Porco, Travis; Lin, Shan C.

    2015-01-01

    Purpose To evaluate the relationship between lens position parameters and intraocular pressure (IOP) reduction after cataract surgery in nonglaucomatous eyes with open angles. Methods The main outcome of the prospective study was percentage of IOP change, which was calculated using the preoperative IOP and the IOP 4 months after cataract surgery in nonglaucomatous eyes with open angles. Lens position (LP), defined as anterior chamber depth (ACD) + 1/2 lens thickness (LT), was assessed preoperatively using parameters from optical biometry. Preoperative IOP, central corneal thickness, ACD, LT, axial length (AXL), and the ratio of preoperative IOP to ACD (PD ratio) were also evaluated as potential predictors of percentage of IOP change. The predictive values of the parameters we found to be associated with the primary outcome were compared. Results Four months after cataract surgery, the average IOP reduction was 2.03 ± 2.42 mm Hg, a 12.74% reduction from the preoperative mean of 14.5 ± 3.05 mm Hg. Lens position was correlated with IOP reduction percentage after adjusting for confounders (P = 0.002). Higher preoperative IOP, shallower ACD, shorter AXL, and thicker LT were significantly associated with percentage of IOP decrease. Although not statistically significant, LP was a better predictor of percentage of IOP change compared to PD ratio, preoperative IOP, and ACD. Conclusions The percentage of IOP reduction after cataract surgery in nonglaucomatous eyes with open angles is greater in more anteriorly positioned lenses. Lens position, which is convenient to compute by basic ocular biometric data, is an accessible predictor with considerable predictive value for postoperative IOP change. PMID:26650901

  11. On the evolution of jet energy and opening angle in strongly coupled plasma

    DOE PAGES

    Chesler, Paul M.; Rajagopal, Krishna

    2016-05-17

    We calculate how the energy and the opening angle of jets in N = 4SYM theory evolve as they propagate through the strongly coupled plasma of that theory. We define the rate of energy loss dEjet/dx and the jet opening angle in a straightforward fashion directly in the gauge theory before calculating both holographically, in the dual gravitational description. In this way, we rederive the previously known result for dEjet/dx without the need to introduce a finite slab of plasma. We obtain a striking relationship between the initial opening angle of the jet, which is to say the opening anglemore » that it would have had if it had found itself in vacuum instead of in plasma, and the thermalization distance of the jet. Via this relationship, we show that N = 4SYM jets with any initial energy that have the same initial opening angle and the same trajectory through the plasma experience the same fractional energy loss. We also provide an expansion that describes how the opening angle of the N = 4SYM jets increases slowly as they lose energy, over the fraction of their lifetime when their fractional energy loss is not yet large. In conclusion, we close by looking ahead toward potential qualitative lessons from our results for QCD jets produced in heavy collisions and propagating through quark-gluon plasma.« less

  12. ESTIMATING LONG GRB JET OPENING ANGLES AND REST-FRAME ENERGETICS

    SciTech Connect

    Goldstein, Adam; Briggs, Michael S.; Burns, Eric

    2016-02-10

    We present a method to estimate the jet opening angles of long duration gamma-ray bursts (GRBs) using the prompt gamma-ray energetics and an inversion of the Ghirlanda relation, which is a correlation between the time-integrated peak energy of the GRB prompt spectrum and the collimation-corrected energy in gamma-rays. The derived jet opening angles using this method and detailed assumptions match well with the corresponding inferred jet opening angles obtained when a break in the afterglow is observed. Furthermore, using a model of the predicted long GRB redshift probability distribution observable by the Fermi Gamma-ray Burst Monitor (GBM), we estimate the probability distributions for the jet opening angle and rest-frame energetics for a large sample of GBM GRBs for which the redshifts have not been observed. Previous studies have only used a handful of GRBs to estimate these properties due to the paucity of observed afterglow jet breaks, spectroscopic redshifts, and comprehensive prompt gamma-ray observations, and we potentially expand the number of GRBs that can be used in this analysis by more than an order of magnitude. In this analysis, we also present an inferred distribution of jet breaks which indicates that a large fraction of jet breaks are not observable with current instrumentation and observing strategies. We present simple parameterizations for the jet angle, energetics, and jet break distributions so that they may be used in future studies.

  13. [Ocular hydrodynamics after phacoemulsification cataract surgery in patients with primary open-angle glaucoma].

    PubMed

    Kalizhnikova, E A; Lebedev, O I; Shchipacheva, O V; Pecheritsa, G G

    Цель - изучить показатели оттока внутриглазной жидкости (ВГЖ) у пациентов с первичной открытоугольной глаукомой при факоэмульсификации катаракты (ФЭК). Материал и методы. В исследовании приняли участие 153 пациента (153 глаза) с катарактой и первичной открытоугольной глаукомой. Пациенты были разделены на 3 группы: 1-я группа - 51 пациент (51 глаз) с катарактой без глаукомы, 2-я группа - 51 пациент (51 глаз) с катарактой и начальной стадией первичной открытоугольной глаукомы, 3-я группа - 51 пациент (51 глаз) с катарактой и развитой стадией первичной открытоугольной глаукомы. До и после операции больным были проведены бесконтактная пневмотонометрия, электронная тонография и тонография с вакуумной компрессией (аппарат Glau-Test60). Всем пациентам была выполнена ФЭК с имплантацией эластичной модели заднекамерной интраокулярной линзы. Срок наблюдения составил 6 мес. Результаты и обсуждение. В результате ФЭК с имплантацией ИОЛ снизился уровень ВГД у пациентов 1-й группы (с катарактой без глаукомы) от 3 до 5 мм рт.ст. в 21,57% случаев, более 5 мм рт.ст. - в 58,8% случаев; у пациентов с начальной и развитой стадиями глаукомы от 3 до 5 мм рт.ст. - в 33,3 и 13,7% случаев, более 5 мм рт.ст. - в 49,02 и 56,9 % наблюдений соответственно. Снижение уровня ВГД при ФЭК обусловлено активацией путей оттока ВГЖ. Заключение. Усиление трабекулярного и увеосклерального пути оттока произошло во всех группах после операции, более значимо у пациентов без глаукомы и в группе больных с начальной стадией заболевания.

  14. Comparison of Newly Diagnosed Ocular Hypertension and Open-Angle Glaucoma: Ocular Variables, Risk Factors, and Disease Severity

    PubMed Central

    Buys, Yvonne M.; Harasymowycz, Paul; Gaspo, Rania; Kwok, Kenneth; Hutnik, Cindy M. L.; Blondeau, Pierre; Birt, Catherine M.; Piemontesi, Robert L. G.; Gould, Lisa F.; Lesk, Mark R.; Ahmed, Iqbal K.

    2012-01-01

    Purpose. To describe the distribution of ocular variables, risk factors, and disease severity in newly diagnosed ocular hypertension (OH) or open-angle glaucoma (OAG). Methods. Eligible subjects underwent a complete history and examination. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) obtained from multiple logistic regression models were used to compare OAG to OH and advanced to early/moderate OAG. Results. 405 subjects were enrolled: 292 (72.1%) with OAG and 113 (27.9%) with OH. 51.7% had early, 27.1% moderate, and 20.9% advanced OAG. The OR for OAG versus OH was 8.19 (P < 0.0001) for disc notch, 5.36 (P < 0.0001) for abnormal visual field, 1.45 (P = 0.001) for worsening mean deviation, 1.91 (P < 0.0001) for increased cupping, 1.03 for increased age (P = 0.030), and 0.36 (P = 0.010) for smoking. Conclusions. Increased age was a risk for OAG, and smoking decreased the risk of OAG compared to OH. Almost half of the OAG subjects had moderate/advanced disease at diagnosis. PMID:21869921

  15. Primary processes in sensory cells: current advances.

    PubMed

    Frings, Stephan

    2009-01-01

    In the course of evolution, the strong and unremitting selective pressure on sensory performance has driven the acuity of sensory organs to its physical limits. As a consequence, the study of primary sensory processes illustrates impressively how far a physiological function can be improved if the survival of a species depends on it. Sensory cells that detect single-photons, single molecules, mechanical motions on a nanometer scale, or incredibly small fluctuations of electromagnetic fields have fascinated physiologists for a long time. It is a great challenge to understand the primary sensory processes on a molecular level. This review points out some important recent developments in the search for primary processes in sensory cells that mediate touch perception, hearing, vision, taste, olfaction, as well as the analysis of light polarization and the orientation in the Earth's magnetic field. The data are screened for common transduction strategies and common transduction molecules, an aspect that may be helpful for researchers in the field.

  16. Pit-like changes of the optic nerve head in open-angle glaucoma.

    PubMed Central

    Radius, R. L.; Maumenee, A. E.; Green, W. R.

    1978-01-01

    Six patients with open-angle glaucoma and acquired pit-like changes in the optic nerve head are presented. In 1 patient evolution of the pit-like defect is documented. In all 6 patients progression of associated visual field deficits is described. It is suggested that such pit-like changes in selected patients with glaucoma may not represent congenital lesions but rather local, progressive nerve head disease, occurring particularly in response to raised intraocular pressure. The management of patients with optic nerve head pitting and the pathogenesis of glaucomatous optic neuropathy are discussed with respect to this observation. Images PMID:666988

  17. Recent advances in primary ciliary dyskinesia.

    PubMed

    Takeuchi, Kazuhiko; Kitano, Masako; Ishinaga, Hajime; Kobayashi, Masayoshi; Ogawa, Satoru; Nakatani, Kaname; Masuda, Sawako; Nagao, Mizuho; Fujisawa, Takao

    2016-06-01

    Primary ciliary dyskinesia (PCD) is a genetic disease inherited in an autosomal recessive manner. The prevalence of PCD is estimated to be 1 in 20,000 live births. Congenital abnormality of the primary cilia results in situs inversus in 50% of patients. Decreased function of motile cilia causes chronic rhinosinusitis, otitis media with effusion, bronchiectasis and infertility. Cases with situs inversus are considered to show "Kartagener's syndrome", and diagnosis is not difficult. However, in cases without situs inversus, the diagnosis is much more troublesome. PCD without situs inversus is thus probably underdiagnosed. Prolonged chronic cough represents an important symptom that is seen in most patients. The diagnosis of PCD requires the presence of the characteristic clinical phenotypes and either: (1) specific ciliary ultrastructural defects identified by transmission electron microscopy in biopsy samples of respiratory epithelium; or (2) identification of mutation in one of the genes known to be associated with PCD. Nasal nitric oxide concentration is extremely low in PCD, and this could be useful for screening of the disease. At present, no fundamental therapies are available for PCD. Diagnosis in the early stages is important to prevent progression of bronchiectasis and deterioration of lung function by guidance for daily life, immunization, cessation of smoking and prompt therapy at the time of respiratory tract infection. Since PCD is inherited in an autosomal-recessive manner, genetic counseling is necessary after definite diagnosis.

  18. iStent trabecular micro-bypass stent for open-angle glaucoma

    PubMed Central

    Le, Kim; Saheb, Hady

    2014-01-01

    Trabecular micro-bypass stents, commonly known as iStents, are micro-invasive glaucoma surgery (MIGS) devices used to treat open-angle glaucoma. Like other MIGS procedures that enhance trabecular outflow, the iStent lowers intraocular pressure (IOP) by creating a direct channel between the anterior chamber and Schlemm’s canal. iStents are typically implanted at the time of phacoemulsification for patients with open-angle glaucoma and visually significant cataracts. This review summarizes the published data regarding the efficacy, safety, and cost considerations of trabecular micro-bypass stents. Most studies found statistically significant reductions in mean IOP and ocular medication use after combined phacoemulsification with single or double iStent implantation. The devices were found to be very safe, with a safety profile similar to that of cataract surgery. Complications were infrequent, with the most common complications being temporary stent obstruction or malposition, which resolved with observation or secondary procedures. Future studies are needed to evaluate long-term outcomes, patient satisfaction, cost effectiveness, and expanded indications. PMID:25284980

  19. Advances in primary lithium liquid cathode batteries

    NASA Astrophysics Data System (ADS)

    Blomgren, George E.

    1989-05-01

    Recent work on cell development and various aspects of cell chemistry and cell development of lithium/thionyl chloride liquid cathode batteries is reviewed. As a result of safety studies, a number of cell sizes can now be considered satisfactory for many applications and the energy densities of these cells is higher than any other developed battery system. Primary batteries operate with low to moderate currents and the anode delay effect appears to be under reasonable control. Reserve cells are in the design stage and operate at high to very high power densities as well as very high energy densities. The nature of the anode film and the operation of the lithium anode has been studied with substantial success and understanding has grown accordingly. Also, studies of the structure of the electrolyte and the effects on the electrolyte of impurities and additives have led to improved understanding in this area as well. Work in progress on new electrolytes is reviewed. The state of the art of mathematical modeling is also discussed and it is expected that this work will continue to develop.

  20. Advanced nurse roles in UK primary care.

    PubMed

    Sibbald, Bonnie; Laurant, Miranda G; Reeves, David

    2006-07-03

    Nurses increasingly work as substitutes for, or to complement, general practitioners in the care of minor illness and the management of chronic diseases. Available research suggests that nurses can provide as high quality care as GPs in the provision of first contact and ongoing care for unselected patients. Reductions in cost are context dependent and rarely achieved. This is because savings on nurses' salaries are often offset by their lower productivity (due to longer consultations, higher patient recall rates, and increased use of tests and investigations). Gains in efficiency are not achieved when GPs continue to provide the services that have been delegated to nurses, instead of focusing on the services that only doctors can provide. Unintended consequences of extending nursing roles include loss of personal continuity of care for patients and increased difficulties with coordination of care as the multidisciplinary team size increases. Rapid access to care is, however, improved. There is a high capital cost involved in moving to multidisciplinary teams because of the need to train staff in new ways of working; revise legislation governing scope of practice; address concerns about legal liability; and manage professional resistance to change. Despite the unintended consequences and the high costs, extending nursing roles in primary care is a plausible strategy for improving service capacity without compromising quality of care or health outcomes for patients.

  1. Induced pluripotent stem cells restore function in a human cell loss model of open-angle glaucoma.

    PubMed

    Abu-Hassan, Diala W; Li, Xinbo; Ryan, Eileen I; Acott, Ted S; Kelley, Mary J

    2015-03-01

    Normally, trabecular meshwork (TM) and Schlemm's canal inner wall endothelial cells within the aqueous humor outflow pathway maintain intraocular pressure within a narrow safe range. Elevation in intraocular pressure, because of the loss of homeostatic regulation by these outflow pathway cells, is the primary risk factor for vision loss due to glaucomatous optic neuropathy. A notable feature associated with glaucoma is outflow pathway cell loss. Using controlled cell loss in ex vivo perfused human outflow pathway organ culture, we developed compelling experimental evidence that this level of cell loss compromises intraocular pressure homeostatic function. This function was restored by repopulation of the model with fresh TM cells. We then differentiated induced pluripotent stem cells (iPSCs) and used them to repopulate this cell depletion model. These differentiated cells (TM-like iPSCs) became similar to TM cells in both morphology and expression patterns. When transplanted, they were able to fully restore intraocular pressure homeostatic function. This successful transplantation of TM-like iPSCs establishes the conceptual feasibility of using autologous stem cells to restore intraocular pressure regulatory function in open-angle glaucoma patients, providing a novel alternative treatment option.

  2. Differential Association of Metabolic Risk Factors with Open Angle Glaucoma according to Obesity in a Korean Population

    PubMed Central

    Kim, Hyun-Ah; Han, Kyungdo; Lee, Yun-Ah; Choi, Jin A; Park, Yong-Moon

    2016-01-01

    The associations of the metabolic syndrome (MetS) with intraocular pressure and primary open angle glaucoma (OAG) have been reported. This study aimed to determine whether a difference in association exists between OAG and metabolic risk factors according to obesity status among Korean adults. A total of 8,816 participants (≥40 years) in the Korea National Health and Nutrition Examination Survey were classified into obese, body mass index (BMI) ≥ 25 kg/m2 and non-obese, BMI < 25 kg/m2. The prevalence of MetS was 40.1% in non-obese OAG and 66.0% in obese OAG. The prevalence of OAG increased with increasing number components for MetS in total population and in non-obese subjects (P < 0.001, respectively), while the prevalence of OAG was not associated with number of components for MetS in obese subjects (P = 0.14). In non-obese individuals, subjects with high triglycerides, high blood pressure (BP), and MetS were more likely to have OAG compared with those without high triglycerides, high BP, and MetS after adjusting for potential confounders. However, MetS or its components exhibited no significant association with glaucoma status in obese individuals. Our study provides understanding on the differences in association of OAG with MetS and its components according to obesity status. PMID:28004731

  3. Induced Pluripotent Stem Cells Restore Function in a Human Cell Loss Model of Open-Angle Glaucoma

    PubMed Central

    Abu-Hassan, Diala W; Li, Xinbo; Ryan, Eileen I; Acott, Ted S; Kelley, Mary J

    2015-01-01

    Normally, trabecular meshwork (TM) and Schlemm's canal inner wall endothelial cells within the aqueous humor outflow pathway maintain intraocular pressure within a narrow safe range. Elevation in intraocular pressure, because of the loss of homeostatic regulation by these outflow pathway cells, is the primary risk factor for vision loss due to glaucomatous optic neuropathy. A notable feature associated with glaucoma is outflow pathway cell loss. Using controlled cell loss in ex vivo perfused human outflow pathway organ culture, we developed compelling experimental evidence that this level of cell loss compromises intraocular pressure homeostatic function. This function was restored by repopulation of the model with fresh TM cells. We then differentiated induced pluripotent stem cells (iPSCs) and used them to repopulate this cell depletion model. These differentiated cells (TM-like iPSCs) became similar to TM cells in both morphology and expression patterns. When transplanted, they were able to fully restore intraocular pressure homeostatic function. This successful transplantation of TM-like iPSCs establishes the conceptual feasibility of using autologous stem cells to restore intraocular pressure regulatory function in open-angle glaucoma patients, providing a novel alternative treatment option. Stem Cells 2015;33:751–761 PMID:25377070

  4. Adherence to treatment in patients with open-angle glaucoma and its related factors

    PubMed Central

    Movahedinejad, Tayebeh; Adib-Hajbaghery, Mohsen

    2016-01-01

    Introduction Lack of adherence to medical treatments typically lead to burdensome consequences such as progressive visual impairment, blindness, and disabilities. This study aimed to determine the adherence to medication in patients with open-angle glaucoma and related factors in patients referred to the Matini Ophthalmology Hospital in Kashan, Iran. Methods A cross-sectional study was conducted from 23 July 2015 to 20 January 2016 on all patients with open-angle glaucoma referred to the Matini Ophthalmology Hospital in Kashan, Iran. A questionnaire was used to gather data about patients’ demographics and factors affecting adherence to medical treatments. The Morisky Medication Adherence Scale was used to evaluate the adherence to glaucoma medication. Results were analyzed using SPSS version 13. Descriptive statistics, chi-square, and logistic regression analysis were used. Results In total, 130 patients with a mean age of 55.36 ± 15.54 were studied. Only 34.6% of patients completely adhered to glaucoma medications. The chi-square test showed that age (p=0.007), education (p=0.01), life entourage (p=0.04), place of residence (p=0.06), average monthly income (p=0.005), the interval between medical visits (p=0.007), problem in scheduling the medical visits (p<0.001), number of medications (p<0.001), lifelong using and side-effects of medications (p<0.001), answers of the physician to the patient’s questions (p<0.001), financial and traveling problems (p<0.001), lack of skill in using eye drops (p<0.001), lack of awareness of glaucoma complications and symptoms (p<0.001), forgetting, fatigue, impatience, believing in uselessness of medications, and lack of support from family (p<0.001) were associated with patients’ adherence. Logistic regression showed that 89% of variance of patients’ adherence to glaucoma medications can be predicted by seven factors: problems in traveling and scheduling medical visits, the large number and side effects of medications

  5. Type 2 Diabetes Mellitus and the Risk of Open-angle Glaucoma

    PubMed Central

    Chopra, Vikas; Varma, Rohit; Francis, Brian A.; Wu, Joanne; Torres, Mina; Azen, Stanley P.

    2016-01-01

    Purpose To examine the relationship between type 2 diabetes mellitus (T2DM) and the risk of having open-angle glaucoma (OAG) in an adult Latino population. Design Population-based cross-sectional study. Participants Latinos 40 years and older (n = 5894) from 6 census tracts in Los Angeles, California. Methods Participants from the Los Angeles Latino Eye Study (LALES), a large population-based study of self-identified adult Latinos, answered an interviewer-administered questionnaire and underwent a clinical and complete ocular examination, including visual field (VF) testing and stereo fundus photography. A participant was defined as having diabetes mellitus (DM) if she or he had a history of being treated for DM, the participant’s glycosylated hemoglobin was measured at 7.0% or higher, or the participant had random blood glucose of 200 mg% or higher. Type 2 DM was defined if the participant was 30 years or older when diagnosed with DM. Open-angle glaucoma was defined as the presence of an open angle and a glaucomatous VF abnormality and/or evidence of glaucomatous optic disc damage in at least one eye. Logistic regression analysis was used to identify the risk of having OAG in persons with T2DM. Main Outcome Measure Prevalence of OAG. Results Of the 5894 participants with complete data, 1157 (19.6%) had T2DM and 288 (4.9%) had OAG. The prevalence of OAG was 40% higher in participants with T2DM than in those without T2DM (age/gender/intraocular pressure–adjusted odds ratio, 1.4; 95% confidence interval, 1.03–1.8; P = 0.03). Trend analysis revealed that a longer duration of T2DM (stratified into 5-year increments) was associated with a higher prevalence of OAG (P<0.0001). Conclusion The presence of T2DM and a longer duration of T2DM were independently associated with a higher risk of having OAG in the LALES cohort. The high prevalences of T2DM and OAG and their association in this fastest growing segment of the United States population have significant

  6. Modern Concepts of the Diagnosis and Treatment of Chronic Open-Angle Glaucoma

    PubMed Central

    Mikelberg, Frederick S.

    1986-01-01

    Chronic open-angle glaucoma is an important cause of blindness in North America. It consists of the triad of elevated intraocular pressure, pathological cupping of the optic nerve head, and visual field loss. Sophisticated techniques have been developed to determine more accurately the health of the optic nerve head and the status of the visual field. Therapy is aimed at lowering intraocular pressure. This includes topical and systemic therapy followed by laser therapy if necessary. Surgery is indicated if laser and medical treatment fail. The family practitioner has an important role to play in screening individuals to detect this disease. The family practitioner should be aware of the systemic and topical side effects of anti-glaucoma medications. ImagesFigure 1Figure 3 PMID:21267101

  7. A Relationship Between Constraint and the Critical Crack Tip Opening Angle

    NASA Technical Reports Server (NTRS)

    Johnston, William M.; James, Mark A.

    2009-01-01

    Of the various approaches used to model and predict fracture, the Crack Tip Opening Angle (CTOA) fracture criterion has been successfully used for a wide range of two-dimensional thin-sheet and thin plate applications. As thicker structure is considered, modeling the full three-dimensional fracture process will become essential. This paper investigates relationships between the local CTOA evaluated along a three-dimensional crack front and the corresponding local constraint. Previously reported tunneling crack front shapes were measured during fracture by pausing each test and fatigue cycling the specimens to mark the crack surface. Finite element analyses were run to model the tunneling shape during fracture, with the analysis loading conditions duplicating those tests. The results show an inverse relationship between the critical fracture value and constraint which is valid both before maximum load and after maximum load.

  8. A single gene for juvenile and middle-age onset open-angle glaucomas confined within a small interval on chromosome 1q

    SciTech Connect

    Raymond, V.; Dumont, M.; Plante, M.

    1994-09-01

    Primary open-angle glaucoma (POAG) encompasses a complex of ocular disease entities characterized by an optic neuropathy causing progressive loss of the visual fields and usually associated with elevated intraocular pressure. POAG can be subdivided into two groups according to age of onset: (1) the more prevalent middle to late-age onset chronic open-angle glaucoma (COAG) diagnosed after age 40 and (2) the less common form, juvenile open-angle glaucoma (JOAG), which occurs between 3 years of age and early adulthood. Susceptibility to either COAG or JOAG has been found to be inherited. We studied 141 members of a huge multigeneration French Canadian family affected with an autosomal dominant form of POAG. Both JOAG and COAG were diagnosed in 43 patients. To first position the disease gene, AFM microsatellites markers specific to chromosome 1q21-q31 were selected since linkage of JOAG to this region was recently demonstrated in two Caucasian families. Tight linkage was observed between the JOAG/COAG phenotype and 7 microsatellite markers on chromosome 1q23-q25; a maximum lod score of 6.62 at {theta}=0 was obtained with AFM278ye5. Using a recombination mapping strategy based on a unique founder effect, a characteristic JOAG/COAG haplotype spanning 12 cM was next recognized between loci D1S196 and D1S212. Two key recombination events in affected patients further confined the disease locus within a 5 cM interval between loci D1S445 and D1S452/D1S210. These results are the first to demonstrate that JOAG and one adult form of POAG map at a single locus on chromosome 1q23-q25. They also provide members of this family with a new diagnostic tool to identify the at-risk individuals.

  9. Tank-Binding Kinase 1 (TBK1) Gene and Open-Angle Glaucomas (An American Ophthalmological Society Thesis)

    PubMed Central

    Fingert, John H.; Robin, Alan L.; Scheetz, Todd E.; Kwon, Young H.; Liebmann, Jeffrey M.; Ritch, Robert; Alward, Wallace L.M.

    2016-01-01

    Purpose To investigate the role of TANK-binding kinase 1 (TBK1) gene copy-number variations (ie, gene duplications and triplications) in the pathophysiology of various open-angle glaucomas. Methods In previous studies, we discovered that copy-number variations in the TBK1 gene are associated with normal-tension glaucoma. Here, we investigated the prevalence of copy-number variations in cohorts of patients with other open-angle glaucomas—juvenile-onset open-angle glaucoma (n=30), pigmentary glaucoma (n=209), exfoliation glaucoma (n=225), and steroid-induced glaucoma (n=79)—using a quantitative polymerase chain reaction assay. Results No TBK1 gene copy-number variations were detected in patients with juvenile-onset open-angle glaucoma, pigmentary glaucoma, or steroid-induced glaucoma. A TBK1 gene duplication was detected in one (0.44%) of the 225 exfoliation glaucoma patients. Conclusions TBK1 gene copy-number variations (gene duplications and triplications) have been previously associated with normal-tension glaucoma. An exploration of other open-angle glaucomas detected a TBK1 copy-number variation in a patient with exfoliation glaucoma, which is the first example of a TBK1 mutation in a glaucoma patient with a diagnosis other than normal-tension glaucoma. A broader phenotypic range may be associated with TBK1 copy-number variations, although mutations in this gene are most often detected in patients with normal-tension glaucoma. PMID:27881886

  10. First-line treatment for elevated intraocular pressure (IOP) associated with open-angle glaucoma or ocular hypertension: focus on bimatoprost

    PubMed Central

    Law, Simon K

    2007-01-01

    The goal of treatment for open-angle glaucoma or ocular hypertension is to improve quality of life through reduction of intraocular pressure (IOP) to preserve visual function. Prostaglandins, as a newer class of ocular hypotensive agents, have been shown to be effective in IOP reduction by the primary mechanism of action of increase the uveoscleral outflow. Bimatoprost is a member this class, but different from the other members by having an ethyl amide group rather than an isopropyl ester at the C-1 carbon of the alpha chain. Bimatoprost used once daily has been shown to be more effect in IOP reduction than other classes of topical ocular hypotensive agents including beta-blockers, carbonic anhydrase inhibitors, and alpha agonists. Comparing with other topical prostaglandins, bimatoprost may be slightly more effective in IOP reduction, but the clinical significance is uncertain. The commonly reported adverse events associated with bimatoprost are localized to the eye and include conjunctival hyperemia, changes in the pigmentation of the periocular skin and iris, and eyelash darkening and growth. It is currently approved by the Food and Drug Administration (FDA) and the European Commission (EC) for first-line therapy for the reduction of elevated IOP in patients with open-angle glaucoma or ocular hypertension. PMID:19668476

  11. Simulation analysis of the effects of an initial cone position and opening angle on a cone-guided implosion

    SciTech Connect

    Yanagawa, T.; Sakagami, H.; Nagatomo, H.

    2013-10-15

    In inertial confinement fusion, the implosion process is important in forming a high-density plasma core. In the case of a fast ignition scheme using a cone-guided target, the fuel target is imploded with a cone inserted. This scheme is advantageous for efficiently heating the imploded fuel core; however, asymmetric implosion is essentially inevitable. Moreover, the effect of cone position and opening angle on implosion also becomes critical. Focusing on these problems, the effect of the asymmetric implosion, the initial position, and the opening angle on the compression rate of the fuel is investigated using a three-dimensional pure hydrodynamic code.

  12. Examining the wake structure in Saturn's rings from microwave observations over varying ring opening angles and wavelengths

    NASA Astrophysics Data System (ADS)

    Dunn, David E.; de Pater, Imke; Molnar, Lawrence A.

    2007-12-01

    Over the last 15 to 20 years several high quality, high resolution data have been taken with the very large array (VLA). These data exhibit a wide range of ring opening angles ( |B|=0 to 26°) and wavelengths ( λ=0.7 to 20 cm). At these wavelengths the primary flux from the rings is scattered saturnian thermal emission, with a small contribution coming from the ring particles' own thermal emission. Much of the data do show signs of asymmetries due to wakes either on the ansae or the portion of the rings which occult the planet. As in previous work, we use our Monte Carlo radiative transfer code including idealized wakes [Dunn, D.E., Molnar, L.A., Fix, J.D., 2002. Icarus 160, 132-160; Dunn, D.E., Molnar, L.A., Niehof, J.T., de Pater, I., Lissauer, J.L., 2004. Icarus 171, 183-198] to model the relative contributions of the scattered and thermal radiation emanating from the rings and compare the results to that seen in the data. Although the models do give satisfactory fits to all of our data, we find that no single model can simulate the data at all different |B| and λ. We find that one model works best for moderate and low |B| and another one at higher |B|. The main difference between these models is the ratio of the wake width to their separation. We similarly find that the 2 cm data require higher density wakes than the longer wavelength data, perhaps caused by a preponderance of somewhat smaller ring material in the wakes. We further find evidence for an increase in the physical temperature of the rings with increasing |B|. Continuous observations are required to determine whether the above results regarding variations in wake parameters with |B| and λ are indeed caused by these parameters, or instead by changes over time.

  13. Literature review and meta-analysis of translaminar pressure difference in open-angle glaucoma

    PubMed Central

    Siaudvytyte, L; Januleviciene, I; Daveckaite, A; Ragauskas, A; Bartusis, L; Kucinoviene, J; Siesky, B; Harris, A

    2015-01-01

    There is increasing evidence in the literature regarding translaminar pressure difference's (TPD) role in the pathophysiology of glaucoma. The optic nerve is exposed not only to intraocular pressure in the eye, but also to intracranial pressure (ICP), as it is surrounded by cerebrospinal fluid in the subarachnoid space. Although pilot studies have identified the potential importance of TPD in glaucoma, limited available data currently prevent a comprehensive description of the role that TPD may have in glaucomatous pathophysiology. In this review, we present all available qualified data from a systematic review of the literature of the role of TPD in open-angle glaucoma (OAG). PubMed (Medline), OVID Medline, ScienceDirect, SpringerLink, and all available library databases were reviewed and subsequent meta-analysis of pooled mean differences are presented where appropriate. Five papers including 396 patients met criteria for inclusion to the analysis. Importantly, we included all observational studies despite differences in ICP measurement methods, as there is no consensus regarding best-practice ICP measurements in glaucoma. Our results show that not only TPD is higher in glaucoma patients compared with healthy subjects, it is related to structural glaucomatous changes of the optic disc. Our analysis suggests further longitudinal prospective studies are needed to investigate the influence of TPD in OAG, with a goal of overcoming methodological weaknesses of previous studies. PMID:26183286

  14. Literature review and meta-analysis of translaminar pressure difference in open-angle glaucoma.

    PubMed

    Siaudvytyte, L; Januleviciene, I; Daveckaite, A; Ragauskas, A; Bartusis, L; Kucinoviene, J; Siesky, B; Harris, A

    2015-10-01

    There is increasing evidence in the literature regarding translaminar pressure difference's (TPD) role in the pathophysiology of glaucoma. The optic nerve is exposed not only to intraocular pressure in the eye, but also to intracranial pressure (ICP), as it is surrounded by cerebrospinal fluid in the subarachnoid space. Although pilot studies have identified the potential importance of TPD in glaucoma, limited available data currently prevent a comprehensive description of the role that TPD may have in glaucomatous pathophysiology. In this review, we present all available qualified data from a systematic review of the literature of the role of TPD in open-angle glaucoma (OAG). PubMed (Medline), OVID Medline, ScienceDirect, SpringerLink, and all available library databases were reviewed and subsequent meta-analysis of pooled mean differences are presented where appropriate. Five papers including 396 patients met criteria for inclusion to the analysis. Importantly, we included all observational studies despite differences in ICP measurement methods, as there is no consensus regarding best-practice ICP measurements in glaucoma. Our results show that not only TPD is higher in glaucoma patients compared with healthy subjects, it is related to structural glaucomatous changes of the optic disc. Our analysis suggests further longitudinal prospective studies are needed to investigate the influence of TPD in OAG, with a goal of overcoming methodological weaknesses of previous studies.

  15. Open angle glaucoma in a case of Type IV Ehler Danlos syndrome: a rarely reported association.

    PubMed

    Mitra, Arijit; Ramakrishnan, R; Kader, Mohideen Abdul

    2014-08-01

    A 26-year-old male presented to us with defective vision in the left eye. He had best corrected visual acuity (BCVA) of hand movement (HM) in right eye and 6/9 in left eye. He had ptosis with ectropion in both eyes and relative afferent pupillary defect (RAPD) in right eye. Intraocular pressure (IOP) was 46 and 44 mmHg in right and left eye, respectively. Fundus showed glaucomatous optic atrophy (GOA) in right eye and cup disc ratio (CDR) of 0.75 with bipolar rim thinning in left eye. Systemic examination showed hyperextensible skin and joints, acrogeria, hypodontia, high arched palate, and varicose veins. He gave history of easy bruising and tendency to fall and history of intestinal rupture 5 years ago for which he had undergone surgery. He was diagnosed as a case of Type IV Ehler-Danlos syndrome (EDS) with open angle glaucoma. He underwent trabeculectomy in both eyes. This is a rare case that shows glaucoma in a patient of EDS Type IV. Very few such cases have been reported in literature.

  16. Open angle glaucoma in a case of Type IV Ehler Danlos syndrome: A rarely reported association

    PubMed Central

    Mitra, Arijit; Ramakrishnan, R.; Kader, Mohideen Abdul

    2014-01-01

    A 26-year-old male presented to us with defective vision in the left eye. He had best corrected visual acuity (BCVA) of hand movement (HM) in right eye and 6/9 in left eye. He had ptosis with ectropion in both eyes and relative afferent pupillary defect (RAPD) in right eye. Intraocular pressure (IOP) was 46 and 44 mmHg in right and left eye, respectively. Fundus showed glaucomatous optic atrophy (GOA) in right eye and cup disc ratio (CDR) of 0.75 with bipolar rim thinning in left eye. Systemic examination showed hyperextensible skin and joints, acrogeria, hypodontia, high arched palate, and varicose veins. He gave history of easy bruising and tendency to fall and history of intestinal rupture 5 years ago for which he had undergone surgery. He was diagnosed as a case of Type IV Ehler-Danlos syndrome (EDS) with open angle glaucoma. He underwent trabeculectomy in both eyes. This is a rare case that shows glaucoma in a patient of EDS Type IV. Very few such cases have been reported in literature. PMID:25230966

  17. Cosmic Ray Energy Determination by the Reduced-Opening Angle Method

    NASA Technical Reports Server (NTRS)

    Gregory, John C.

    1998-01-01

    The reduced opening angle technique offers a simple way with minimal model dependence to measure cosmic ray energies over a broad range with out any normalization uncertainties. The emulsion film and CR39 detectors proposed are well established techniques and should perform adequately. The analysis method depends on accurate automatic scanning of the CR39 plates. UAH have developed such a capability. With the proposed geometry energy measurements to approx. 5 TeV/a can be made. The expected iron event rate (E greater than or equal to 500 GeV/a) is 10/sq m day. The expected energy resolution, from accelerator calibrations at 200 GeV/a, is -50% to +80%. Since the absolute flux has some sensitivity to the assumed power law index it is essential that good energy resolution is obtained. The expected charge resolution is approx. 0.3 charge units for the CNO group falling to approx. 1 charge unit for the iron group. A suitable event trigger would be a measurable (greater than 2 micrometer) deflected heavy (Z greater than 2) fragment. One potential background is electromagnetic dissociation that predominantly couples to individual protons or alphas. Although the cross- sections can be appreciable such events will not pass the event trigger.

  18. Aging changes of the optic nerve head in relation to open angle glaucoma

    PubMed Central

    Garway-Heath, D; Wollstein, G; Hitchings, R

    1997-01-01

    AIMS—To determine the age related changes in optic nerve head structure in a group of normal subjects and assess the significance of any changes in relation to those found in open angle glaucoma.
METHODS—A group of 88 white volunteers and friends and spouses of patients with a normal visual field and normal intraocular pressure was studied. Two different imaging and measurement devices were used (computer assisted planimetry and scanning laser ophthalmoscopy), and the results from each were compared. Measurements were made of the optic disc, optic cup, and neuroretinal rim areas, and the vertical optic disc diameter and cup/disc diameter ratio.
RESULTS—Neuroretinal rim area declined at the rate of between 0.28% and 0.39% per year. Vertical optic cup diameter and optic cup area increased with age. The mean cup/disc diameter ratio increased by about 0.1 between the ages of 30 and 70 years.
CONCLUSIONS—Age related changes are significant and measurable, and should be taken into account when assessing the glaucoma suspect, and when estimating the rate of progression of glaucomatous optic neuropathy in patients with established disease.

 PMID:9486023

  19. Management of locally advanced primary mediastinal synovial sarcoma

    PubMed Central

    Chatterjee, Ambarish S; Kumar, Rajiv; Purandare, Nilendu; Jiwnani, Sabita; Karimundackal, George; Pramesh, CS

    2017-01-01

    Primary mediastinal synovial sarcoma (PMSS) is a relatively rare disease, and patients are treated predominantly with surgery for resectable disease. Management of locally advanced borderline resectable and unresectable PMSS is not only challenging but also lacks standard guidelines. We present three patients with PMSS, who were unresectable or borderline resectable at presentation and were treated with neoadjuvant chemotherapy followed by surgery and postoperative radiotherapy. PMID:28360472

  20. Recent advances in primary palate and midface morphogenesis research.

    PubMed

    Diewert, V M; Wang, K Y

    1992-01-01

    During the sixth week of human development, the primary palate develops as facial prominences enlarge around the nasal pits to form the premaxillary region. Growth of craniofacial components changes facial morphology and affects the extent of contact between the facial prominences. Our recent studies have focused on developing methods to analyze growth of the primary palate and the craniofacial complex to define morphological phases of normal development and to determine alterations leading to cleft lip malformation. Analysis of human embryos in the Carnegie Embryology Collection and mouse embryos of cleft lip and noncleft strains showed that human and mouse embryos have similar phases of primary palate development: first, an epithelial seam, the nasal fin, forms; then a mesenchymal bridge develops through the nasal fin and enlarges rapidly. A robust mesenchymal bridge must form between the facial prominences before advancing midfacial growth patterns tend to separate the facial components as the medial nasal region narrows and elongates, the nasal pits narrow, and the primary choanae (posterior nares) open posterior to the primary palate. In mouse strains with cleft lip gene, maxillary growth, nasal fin formation, and mesenchymal replacement of the nasal fin were all delayed compared with noncleft strains of mice. Successful primary palate formation involves a sequence of local cellular events that are closely timed with spatial changes associated with craniofacial growth that must occur within a critical developmental period.

  1. Numerical study of pressure fluctuations in different guide vanes' opening angle in pump mode of a pump turbine

    NASA Astrophysics Data System (ADS)

    Sun, Y. K.; Zuo, Z. G.; Liu, S. H.; Liu, J. T.; Wu, Y. L.

    2012-11-01

    A numerical model based on a pumped storage power station was built to develop the numerical simulation, to analyze the pressure fluctuations in a pump turbine in different guide vanes' opening angle. The different guide vanes' opening angles were simulated using the SST k-ω turbulence model and SIMPLEC Pressure-Velocity coupling scheme. The pressure sensor were placed in mainly three positions, they are: bottom ring between runner and the wicket gates, downstream and left side in the draft tube cone below the runner. All the peak to peak values of pressure fluctuation meet signal probability of 97%. The frequency is gained by Fast Fourier Transform. The pressure fluctuations in different positions of the model in pump condition were showed when the guide vanes' opening angels were different. The simulation results confirmed the results gained in model tests. The results show that pressure fluctuations in design opening angle were much lower than those in off design opening angle. The main source of pressure fluctuations between runner and guide vanes is rotor stator interaction. While a lower frequency is the main frequency of the pressure fluctuation in draft tube.

  2. Corneal changes after a single session of selective laser trabeculoplasty for open-angle glaucoma

    PubMed Central

    Lee, J W Y; Chan, J C H; Chang, R T; Singh, K; Liu, C C L; Gangwani, R; Wong, M O M; Lai, J S M

    2014-01-01

    Purpose To investigate the changes in endothelial cell count, central corneal thickness (CCT), and refractive error after a session of selective laser trabeculoplasty (SLT) for open angle glaucoma (OAG). Methods This prospective cohort study recruited 111 eyes of 66 consecutive subjects with OAG. Subjects received SLT to 360° of the trabecular meshwork. Endothelial cell count, CCT, and spherical equivalent were measured at baseline before SLT as well as at 1 week and 1 month post SLT. A repeated measure nested ANOVA with Tukey's multiple comparison test was performed to compare the outcome measures before and after SLT. Results In 111 eyes of 66 subjects, the mean number of laser applications per treatment was 166.9±41.4 with a mean energy level of 1.0±0.07 mJ. The mean endothelial cell count decreased significantly from 2465.0±334.0 cells/mm2 at baseline to 2355.0±387.0 cells/mm2 at 1 week (P=0.0004) but increased to baseline levels at 1 month post SLT (2424.0±379.4 cells/mm2, P=0.3). The CCT, which decreased from a baseline of 549.4±37.6 to 543.9±40.2 μm at 1 week post SLT (P=0.02), also returned to the baseline level by 1 month (P=0.2). The spherical equivalent was static from baseline. A positive correlation was found between total laser energy and CCT at 1 month post treatment (r=0.3, P=0.005). Conclusion The transient reductions in endothelial cell count and CCT following SLT returned to baseline levels 1 month after the procedure. Patients undergoing SLT should be aware of the risk of potential corneal changes. PMID:24136571

  3. Dementia is associated with open-angle glaucoma: a population-based study

    PubMed Central

    Chung, S-D; Ho, J-D; Chen, C-H; Lin, H-C; Tsai, M-C; Sheu, J-J

    2015-01-01

    Purpose Previous epidemiologic studies that focused on the association between open-angle glaucoma (OAG) and dementia showed inconsistent results. In the present study, we explored the association between OAG and dementia in an ethnic Chinese (ie, Taiwanese) population using a population-based data set. Methods We retrieved data on study subjects for this case-control study from the Longitudinal Health Insurance Database 2000. We identified 7770 patients who had a diagnosis of dementia as cases, and 7770 subjects matched in terms of sex and age, which were randomly extracted as controls. A conditional logistic regression conditioned on age group, sex, and index year was used to assess the association of dementia with previously diagnosed OAG among the sampled patients. Results Of 15 540 patients, 1.70% had prior OAG, including 2.02% of the dementia group and 1.38% of the controls. After adjusting for patient socioeconomic characteristics and comorbid medical disorders, dementia patients were more likely to have had prior OAG than controls (odds ratio (OR): 1.44; 95% confidence interval (CI): 1.12–1.85; P<0.01). In addition, female dementia patients were more likely to have had prior OAG than controls (OR: 1.93; 95% CI: 1.35–2.77; P<0.001), whereas no statistical difference in prior OAG between male dementia patients and controls was found. Conclusions Female dementia patients were associated with a higher proportion of prior OAG than were the controls. PMID:26160529

  4. SELECTION EFFECTS ON THE OBSERVED REDSHIFT DEPENDENCE OF GAMMA-RAY BURST JET OPENING ANGLES

    SciTech Connect

    Lu Ruijing; Wei Junjie; Liang Enwei; Qin Shufu

    2012-02-01

    An apparent redshift dependence of the jet opening angles ({theta}{sub j}) of gamma-ray bursts (GRBs) is observed from the current GRB sample. We investigate whether this dependence can be explained with instrumental selection effects and observational biases by a bootstrapping method. Assuming that (1) the GRB rate follows the star formation history and the cosmic metallicity history and (2) the intrinsic distributions of the jet-corrected luminosity (L{sub {gamma}}) and {theta}{sub j} are a Gaussian or a power-law function, we generate a mock Swift/Burst Alert Telescope (BAT) sample by considering various instrumental selection effects, including the flux threshold and the trigger probability of BAT, the probabilities of a GRB jet pointing to the instrument solid angle, and the probability of redshift measurement. Our results reproduce the observed {theta}{sub j} - z dependence well. We find that in the case of L{sub {gamma}}{proportional_to}{theta}{sup 2}{sub j} good consistency between the mock and observed samples can be obtained, indicating that both L{sub {gamma}} and {theta}{sub j} are degenerate for a flux-limited sample. The parameter set (L{sub {gamma}}, {theta}{sub j}) = (4.9 Multiplication-Sign 10{sup 49} erg s{sup -1}, 0.054 rad) gives the best consistency for the current Swift GRB sample. Considering the beaming effect, the derived intrinsic local GRB rate is accordingly 2.85 Multiplication-Sign 10{sup 2} Gpc{sup -3} yr{sup -1}, inferring that {approx}0.59% of Type Ib/c supernovae may be accompanied by a GRB.

  5. The faster the narrower: characteristic bulk velocities and jet opening angles of gamma-ray bursts

    NASA Astrophysics Data System (ADS)

    Ghirlanda, G.; Ghisellini, G.; Salvaterra, R.; Nava, L.; Burlon, D.; Tagliaferri, G.; Campana, S.; D'Avanzo, P.; Melandri, A.

    2013-01-01

    The jet opening angle θjet and the bulk Lorentz factor Γ0 are crucial parameters for the computation of the energetics of gamma-ray bursts (GRBs). From the ˜30 GRBs with measured θjet or Γ0 it is known that (i) the real energetic Eγ, obtained by correcting the isotropic equivalent energy Eiso for the collimation factor ˜ θ2jet, is clustered around 1050-1051 erg and it is correlated with the peak energy Ep of the prompt emission and (ii) the comoving frame E'p and E'γ are clustered around typical values. Current estimates of Γ0 and θjet are based on incomplete data samples and their observed distributions could be subject to biases. Through a population synthesis code we investigate whether different assumed intrinsic distributions of Γ0 and θjet can reproduce a set of observational constraints. Assuming that all bursts have the same E'p and E'γ in the comoving frame, we find that Γ0 and θjet cannot be distributed as single power laws. The best agreement between our simulation and the available data is obtained assuming (a) log-normal distributions for θjet and Γ0 and (b) an intrinsic relation between the peak values of their distributions, i.e. θjet2.5Γ0 = const. On average, larger values of Γ0 (i.e. the `faster' bursts) correspond to smaller values of θjet (i.e. the `narrower'). We predict that ˜6 per cent of the bursts that point to us should not show any jet break in their afterglow light curve since they have sin θjet < 1/Γ0. Finally, we estimate that the local rate of GRBs is ˜0.3 per cent of all local Type Ib/c supernova (SNIb/c) and ˜4.3 per cent of local hypernovae, i.e. SNIb/c with broad lines.

  6. A Decade of Short-duration Gamma-Ray Burst Broadband Afterglows: Energetics, Circumburst Densities, and Jet Opening Angles

    NASA Astrophysics Data System (ADS)

    Fong, W.; Berger, E.; Margutti, R.; Zauderer, B. A.

    2015-12-01

    We present a comprehensive catalog and analysis of broadband afterglow observations for 103 short-duration gamma-ray bursts (GRBs), comprised of all short GRBs from 2004 November to 2015 March with prompt follow-up observations in the X-ray, optical, near-infrared (NIR), and/or radio bands. These afterglow observations have uncovered 71 X-ray detections, 30 optical/NIR detections, and 4 radio detections. Employing the standard afterglow synchrotron model, we perform joint probability analyses for a subset of 38 short GRBs with well-sampled light curves to infer the burst isotropic-equivalent energies and circumburst densities. For this subset, we find median isotropic-equivalent γ-ray and kinetic energies of Eγ,iso ≈ 2 × 1051 erg, and EK,iso ≈ (1-3) × 1051 erg, respectively, depending on the values of the model input parameters. We further find that short GRBs occur in low-density environments, with a median density of n ≈ (3-15) × 10-3 cm-3, and that ≈80%-95% of bursts have densities of n ≲ 1 cm-3. We investigate trends between the circumburst densities and host galaxy properties, and find that events located at large projected offsets of ≳10 effective radii from their hosts exhibit particularly low densities of n ≲ 10-4 cm-3, consistent with an intergalactic medium-like environment. Using late-time afterglow data for 11 events, we find a median jet opening angle of θj = 16 ± 10°. We also calculate a median beaming factor of fb ≈ 0.04, leading to a beaming-corrected total energy release of Etrue ≈ 1.6 × 1050 erg. Furthermore, we calculate a beaming-corrected event rate of {{R}}{{true}}={270}-180+1580 Gpc-3 yr-1, or ≈ {8}-5+47 yr-1 within a 200 Mpc volume, the Advanced LIGO/Virgo typical detection distance for NS-NS binaries.

  7. A prospective 3-year follow-up trial of implantation of two trabecular microbypass stents in open-angle glaucoma

    PubMed Central

    Donnenfeld, Eric D; Solomon, Kerry D; Voskanyan, Lilit; Chang, David F; Samuelson, Thomas W; Ahmed, Iqbal Ike K; Katz, L Jay

    2015-01-01

    Purpose To evaluate 3-year safety and intraocular pressure (IOP) following two trabecular microbypass stents in phakic and pseudophakic subjects with open-angle glaucoma (OAG) not controlled on preoperative medication. Patients and methods In this prospective pilot study, phakic or pseudophakic subjects with OAG and IOP between 18 mmHg and 30 mmHg on one preoperative topical ocular hypotensive medication underwent medication washout. Thirty-nine qualified subjects with preoperative unmedicated IOP ≥22 mmHg and ≤38 mmHg received two stents. Postoperative examinations were scheduled at Day 1, Week 1, Months 1, 3, 6, and 12, and semiannually through Month 60. Ocular hypotensive medication was considered if postoperative IOP exceeded 21 mmHg. IOP, medication use, and safety were assessed at each visit. Subject follow-up through Month 36 was completed. Results Thirty-six eyes (92.3%; 95% confidence interval [CI] 79.1%, 98.4%) achieved the primary efficacy end point of Month 12 reduction in IOP ≥20% from baseline (unmedicated IOP) without ocular hypotensive medication. Four subjects required medication during the Month 36 follow-up period. Mean IOP at 36 months for subjects not taking medication was 15.2 mmHg. At 36 months, subjects sustained mean IOP decrease of 9.1±2.7 mmHg (95% CI 8.0 mmHg, 10.14 mmHg), or 37% IOP reduction, from unmedicated baseline IOP. Compared to preoperative medicated IOP, subjects had mean reduction at Month 36 of 5.5±2.7 mmHg (95% CI 4.5 mmHg, 6.6 mmHg), or 26% reduction. Both measures of IOP reduction were highly significant (P<0.001). Other than one case of early postoperative hyphema that resolved at 1 week, no postoperative adverse events were attributed to stent implantation. Conclusion In a pilot study, two trabecular microbypass stents to treat OAG subjects on one preoperative medication provided statistically significant, sustained, and safe reduction of IOP to ≤15 mmHg without medication through 36 months. PMID:26604675

  8. Retinal and choroidal oxygen saturation of the optic nerve head in open-angle glaucoma subjects by multispectral imaging

    PubMed Central

    Li, Gai-yun; Al-wesabi, Samer abdo; Zhang, Hong

    2016-01-01

    Abstract The aim of this study was to determine whether differences exist in oxygen supply to the optic nerve head (ONH) from the retinal and choroidal vascular layers in patients with primary open angle glaucoma (POAG) using multispectral imaging (MSI).This ia an observational, cross-sectional study. Multispectral images were acquired from 38 eyes of 19 patients with POAG, and 42 healthy eyes from 21 matched volunteers with Annidis’ RHA multispectral digital ophthalmoscopy. Superficial and deeper oxygen saturation of the optic disc was represented by the mean gray scale values on the retinal and choroidal oxy-deoxy maps, respectively. Statistical analysis was performed to detect differences in ONH oxygen saturation between the 2 groups. Oxygen saturation levels in the eyes of POAG patients with severe glaucoma were compared to those of fellow eyes from the same subjects. Linear correlation analysis was performed to assess the association between ONH oxygen saturation and systemic and ocular parameters. No statistical difference was found in retinal and choroidal oxygen saturation between the POAG and control groups. In the glaucoma patients, retinal oxygen saturation was lower for eyes with worse visual fields than in those with good visual fields (t = 4.009, P = 0.001). In POAG patients, retinal oxygen saturation was dependent on mean defect of visual field and retinal nerve fiber layer thickness (RNFLT) (r = 0.511, 0.504, P = 0.001, 0.001, respectively), whereas the choroid vasculature oxygen saturation was inversely related to RNFLT (r = −0.391, P = 0.015). An age-dependent increase in retinal oxygen saturation was found for both the POAG and control groups (r = 0.473, 0.410, P = 0.007, 0.003, respectively). MSI revealed a significant correlation between functional and structural impairments in glaucoma and retinal oxygen saturation. MSI could provide objective assessments of perfusion impairments of the glaucomatous ONH

  9. Retinal and choroidal oxygen saturation of the optic nerve head in open-angle glaucoma subjects by multispectral imaging.

    PubMed

    Li, Gai-Yun; Al-Wesabi, Samer Abdo; Zhang, Hong

    2016-12-01

    The aim of this study was to determine whether differences exist in oxygen supply to the optic nerve head (ONH) from the retinal and choroidal vascular layers in patients with primary open angle glaucoma (POAG) using multispectral imaging (MSI).This ia an observational, cross-sectional study.Multispectral images were acquired from 38 eyes of 19 patients with POAG, and 42 healthy eyes from 21 matched volunteers with Annidis' RHA multispectral digital ophthalmoscopy. Superficial and deeper oxygen saturation of the optic disc was represented by the mean gray scale values on the retinal and choroidal oxy-deoxy maps, respectively. Statistical analysis was performed to detect differences in ONH oxygen saturation between the 2 groups. Oxygen saturation levels in the eyes of POAG patients with severe glaucoma were compared to those of fellow eyes from the same subjects. Linear correlation analysis was performed to assess the association between ONH oxygen saturation and systemic and ocular parameters.No statistical difference was found in retinal and choroidal oxygen saturation between the POAG and control groups. In the glaucoma patients, retinal oxygen saturation was lower for eyes with worse visual fields than in those with good visual fields (t = 4.009, P = 0.001). In POAG patients, retinal oxygen saturation was dependent on mean defect of visual field and retinal nerve fiber layer thickness (RNFLT) (r = 0.511, 0.504, P = 0.001, 0.001, respectively), whereas the choroid vasculature oxygen saturation was inversely related to RNFLT (r = -0.391, P = 0.015). An age-dependent increase in retinal oxygen saturation was found for both the POAG and control groups (r = 0.473, 0.410, P = 0.007, 0.003, respectively).MSI revealed a significant correlation between functional and structural impairments in glaucoma and retinal oxygen saturation. MSI could provide objective assessments of perfusion impairments of the glaucomatous ONH. This is a

  10. The Influence of Structure Heights and Opening Angles of Micro- and Nanocones on the Macroscopic Surface Wetting Properties

    PubMed Central

    Schneider, Ling; Laustsen, Milan; Mandsberg, Nikolaj; Taboryski, Rafael

    2016-01-01

    We discuss the influence of surface structure, namely the height and opening angles of nano- and microcones on the surface wettability. We show experimental evidence that the opening angle of the cones is the critical parameter on sample superhydrophobicity, namely static contact angles and roll-off angles. The textured surfaces are fabricated on silicon wafers by using a simple one-step method of reactive ion etching at different processing time and gas flow rates. By using hydrophobic coating or hydrophilic surface treatment, we are able to switch the surface wettability from superhydrophilic to superhydrophobic without altering surface structures. In addition, we show examples of polymer replicas (polypropylene and poly(methyl methacrylate) with different wettability, fabricated by injection moulding using templates of the silicon cone-structures. PMID:26892169

  11. The Influence of Structure Heights and Opening Angles of Micro- and Nanocones on the Macroscopic Surface Wetting Properties

    NASA Astrophysics Data System (ADS)

    Schneider, Ling; Laustsen, Milan; Mandsberg, Nikolaj; Taboryski, Rafael

    2016-02-01

    We discuss the influence of surface structure, namely the height and opening angles of nano- and microcones on the surface wettability. We show experimental evidence that the opening angle of the cones is the critical parameter on sample superhydrophobicity, namely static contact angles and roll-off angles. The textured surfaces are fabricated on silicon wafers by using a simple one-step method of reactive ion etching at different processing time and gas flow rates. By using hydrophobic coating or hydrophilic surface treatment, we are able to switch the surface wettability from superhydrophilic to superhydrophobic without altering surface structures. In addition, we show examples of polymer replicas (polypropylene and poly(methyl methacrylate) with different wettability, fabricated by injection moulding using templates of the silicon cone-structures.

  12. EP3/FP dual receptor agonist ONO-9054 administered morning or evening to patients with open-angle glaucoma or ocular hypertension: results of a randomised crossover study

    PubMed Central

    Berlin, Michael S; Rowe-Rendleman, Cheryl; Ahmed, Ike; Ross, Douglas T; Fujii, Akifumi; Ouchi, Takafumi; Quach, Christine; Wood, Andrew; Ward, Caroline L

    2016-01-01

    Background/aims The novel prostaglandin E (EP) 3 and prostaglandin F (FP) receptor agonist ONO-9054 is effective in lowering intraocular pressure (IOP) in patients with ocular hypertension and open-angle glaucoma when administered once daily. This study compares the effects of morning (AM) versus evening (PM) dosing of ONO-9054 on tolerability and IOP lowering. Methods This was a single-centre, randomised, double-masked, two-sequence, placebo-controlled crossover study in 12 subjects with bilateral primary open-angle glaucoma or ocular hypertension. Two 14-day crossover regimens were separated by a 2-week washout: ONO-9054 (1 drop to each eye) in the morning (07:00) and vehicle in the evening (19:00) and vice versa. IOP was measured multiple times during select days. Ocular examinations also evaluated safety and tolerability. Results Mild ocular hyperaemia, reported by six subjects with PM dosing, was the most frequent adverse event. Mild to moderate dryness was also slightly more frequent after PM dosing. Maximum IOP reduction from baseline occurred on day 2 with decreases from baseline of −7.4 mm Hg (−30.8%) for AM dosing and −9.1 mm Hg, (−38.0%) for PM dosing; after 14 days, mean reduction in IOP was −6.8 mm Hg (−28.6%) for AM dosing and −7.5 mm Hg (−31.0%) for PM dosing. Conclusions PM dosing of ONO-0954 was associated with a slightly increased frequency of mild hyperaemia and mild to moderate dryness. Both dosing schedules provided sustained reduction in IOP. Trial registration number NCT01670266. PMID:26453641

  13. Trabecular-iris circumference volume in open angle eyes using swept-source fourier domain anterior segment optical coherence tomography.

    PubMed

    Rigi, Mohammed; Blieden, Lauren S; Nguyen, Donna; Chuang, Alice Z; Baker, Laura A; Bell, Nicholas P; Lee, David A; Mankiewicz, Kimberly A; Feldman, Robert M

    2014-01-01

    Purpose. To introduce a new anterior segment optical coherence tomography parameter, trabecular-iris circumference volume (TICV), which measures the integrated volume of the peripheral angle, and establish a reference range in normal, open angle eyes. Methods. One eye of each participant with open angles and a normal anterior segment was imaged using 3D mode by the CASIA SS-1000 (Tomey, Nagoya, Japan). Trabecular-iris space area (TISA) and TICV at 500 and 750 µm were calculated. Analysis of covariance was performed to examine the effect of age and its interaction with spherical equivalent. Results. The study included 100 participants with a mean age of 50 (±15) years (range 20-79). TICV showed a normal distribution with a mean (±SD) value of 4.75 µL (±2.30) for TICV500 and a mean (±SD) value of 8.90 µL (±3.88) for TICV750. Overall, TICV showed an age-related reduction (P = 0.035). In addition, angle volume increased with increased myopia for all age groups, except for those older than 65 years. Conclusions. This study introduces a new parameter to measure peripheral angle volume, TICV, with age-adjusted normal ranges for open angle eyes. Further investigation is warranted to determine the clinical utility of this new parameter.

  14. E-2D Advanced Hawkeye: primary flight display

    NASA Astrophysics Data System (ADS)

    Paolillo, Paul W.; Saxena, Ragini; Garruba, Jonathan; Tripathi, Sanjay; Blanchard, Randy

    2006-05-01

    This paper is a response to the challenge of providing a large area avionics display for the E-2D AHE aircraft. The resulting display design provides a pilot with high-resolution visual information content covering an image area of almost three square feet (Active Area of Samsung display = 33.792cm x 27.0336 cm = 13.304" x 10.643" = 141.596 square inches = 0.983 sq. ft x 3 = 2.95 sq. ft). The avionics display application, design and performance being described is the Primary Flight Display for the E-2D Advanced Hawkeye aircraft. This cockpit display has a screen diagonal size of 17 inches. Three displays, with minimum bezel width, just fit within the available instrument panel area. The significant design constraints of supporting an upgrade installation have been addressed. These constraints include a display image size that is larger than the mounting opening in the instrument panel. This, therefore, requires that the Electromagnetic Interference (EMI) window, LCD panel and backlight all fit within the limited available bezel depth. High brightness and a wide dimming range are supported with a dual mode Cold Cathode Fluorescent Tube (CCFT) and LED backlight. Packaging constraints dictated the use of multiple U shaped fluorescent lamps in a direct view backlight design for a maximum display brightness of 300 foot-Lamberts. The low intensity backlight levels are provided by remote LEDs coupled through a fiber optic mesh. This architecture generates luminous uniformity within a minimum backlight depth. Cross-cockpit viewing is supported with ultra-wide field-of-view performance including contrast and the color stability of an advanced LCD cell design supports. Display system design tradeoffs directed a priority to high optical efficiency for minimum power and weight.

  15. Advanced primary peritoneal carcinoma: clinicopathological and prognostic factor analyses

    PubMed Central

    Zhang, Chao; Li, Xiao-ping; Cui, Heng; Shen, Dan-hua; Wei, Li-hui

    2008-01-01

    Objective: To investigate the factors favoring a positive prognosis for advanced primary peritoneal carcinoma (PPC). Methods: Twenty-four cases meeting the criteria for PPC were analyzed retrospectively for the clinicopathologic profiles. Immunohistochemistry was used to determine the expressions of p53, Top2α, Ki-67 and Her-2/neu. Then all these clinicopathological factors and molecular markers were correlated with the prognosis. Results: There were 15 cases of primary peritoneal serous papillary carcinoma (PPSPC), 6 cases of mixed epithelial carcinoma (MEC) and 3 cases of malignant mixed Mullerian tumor (MMMT). All patients underwent cytoreductive surgery with optimal debulking achieved in 3 cases. Among those receiving first-line chemotherapy, 13 patients received the TP regimen (paclitaxel-cisplatin or carboplatin) and 7 patients received the PAC regimen (cisplatin-doxorubicin-cyclophosphamide). The median overall survival of all patients was 42 months, while the breakdown for survival time for patients with PPSPC, MMT and MEC was 44, 13 and 19 months, respectively. The expressions of p53, Top2α and Ki-67 were all demonstrated in 11 cases respectively. None showed the expression of Her-2/neu. There were significant differences in the median survival between patients with PPSPC and those with MMMT (44 months vs 13 months, P<0.05), also between patients receiving TP combination and those receiving the PAC regimen (75 months vs 28 months, P<0.05). Another significant difference in the median progression-free survival (PFS) was identified between patients with positive p53 immunostaining and those with negative p53 immunostaining (15 months vs 47 months, P<0.05), whereas age, menopausal status, residual tumor size and the other molecular factors did not significantly impact survival. Conclusion: Patients with PPC should be treated with a comprehensive management plan including appropriate cytoreductive surgery and responsive chemotherapy. Overestimating an

  16. [Macular choroidal blood flow in concurrent age-related macular degeneration and primary open-angle glaucoma].

    PubMed

    Panova, I E; Ermak, E M; Shaimova, T A; Shaimova, V A

    2016-01-01

    Нарушения внутриглазного кровотока — один из значимых патогенетических факторов в развитии первичной открытоугольной глаукомы (ПОУГ) и возрастной макулярной дистрофии (ВМД). Вместе с тем работы по изучению особенностей гемодинамики на уровне хориоидального сегмента сосудистого русла при сочетанной патологии — ВМД и ПОУГ — отсутствуют. Цель исследования — выявить отличительные характеристики хориоидального кровотока в макулярной зоне при сочетанной патологии — ВМД и ПОУГ — и обосновать их патогенетическое значение в развитии заболевания. Материал и методы. Методом ультразвуковой дуплексной допплерографии исследованы показатели хориоидального кровотока в макулярной зоне с оценкой уровня кровоснабжения у 54 пациентов (102 глаза). Выделены 3 исследовательские группы: 1-я — 38 глаз с сочетанной патологией — ВМД и ПОУГ, 2-я — 41 глаз с ВМД без признаков заболеваний зрительного нерва, 3-я — 23 глаза с ПОУГ без признаков ВМД. В 1-й и 2-й группах выделены подгруппы: А — атрофическая форма, Б — друзы макулы. Средний возраст — 78,7±8,4 года. Определяемые параметры кровотока: пиковая систолическая скорость (peak systolic velocity — Vps), конечная диастолическая скорость (end-diastolic velocity — Ved), усредненная по времени максимальная скорость кровотока (time-averaged maximum velocity — Vtamax), индекс резистентности (resistive index — RI). Результаты. Установлено, что в 1-й, 3-й группах и подгруппе 2А формируется гипоперфузионный тип хориоидального кровотока в макулярной зоне (снижение Vtamax) с развитием некомпенсированного перфузионного дефицита на фоне напряжения механизмов ауторегуляции (снижение Vps, Ved, сниженные или нормальные значения RI). У больных подгруппы 2Б достоверно чаще формируется гиперперфузионный тип хориоидального кровотока (повышение Vps, Ved, Vtamax, RI). Заключение. Сочетанная патология — ВМД и ПОУГ — характеризуется гипоперфузионным типом хориоидального кровотока в макулярной зоне, что приводит к нарушению трофики нейросенсорной сетчатки и предопределяет возможность утяжеления течения ВМД с прогрессированием атрофической формы.

  17. Brinzolamide/brimonidine: a review of its use in patients with open-angle glaucoma or ocular hypertension.

    PubMed

    Greig, Sarah L; Deeks, Emma D

    2015-03-01

    Brinzolamide 1 %/brimonidine 0.2 % ophthalmic suspension (Simbrinza(®)) is a fixed-combination of a carbonic anhydrase inhibitor and an α2-adrenergic receptor agonist that is indicated for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension in both the USA and EU (with the EU indication restricted to patients for whom monotherapy provides insufficient IOP reduction). In phase III randomized trials, both three-times-daily and twice-daily administration of brinzolamide/brimonidine provided significantly greater IOP-lowering efficacy over 3-6 months than either of its individual components alone, and twice-daily brinzolamide/brimonidine was noninferior to concomitant administration of brinzolamide plus brimonidine over 6 months in this regard. Brinzolamide/brimonidine was generally well tolerated, with a tolerability profile that was consistent with its individual components and with no unexpected safety findings. Therefore, brinzolamide/brimonidine is an effective treatment option for patients with open-angle glaucoma or ocular hypertension, providing a convenient alternative for those patients who require multiple IOP-lowering medications. Brinzolamide/brimonidine is the first available fixed-combination that does not contain timolol, and maybe particularly suited to patients with comorbidities that restrict treatment with β-adrenergic receptor antagonists.

  18. A Challenging Surgical Approach to Locally Advanced Primary Urethral Carcinoma

    PubMed Central

    Lucarelli, Giuseppe; Spilotros, Marco; Vavallo, Antonio; Palazzo, Silvano; Miacola, Carlos; Forte, Saverio; Matera, Matteo; Campagna, Marcello; Colamonico, Ottavio; Schiralli, Francesco; Sebastiani, Francesco; Di Cosmo, Federica; Bettocchi, Carlo; Di Lorenzo, Giuseppe; Buonerba, Carlo; Vincenti, Leonardo; Ludovico, Giuseppe; Ditonno, Pasquale; Battaglia, Michele

    2016-01-01

    Abstract Primary urethral carcinoma (PUC) is a rare and aggressive cancer, often underdetected and consequently unsatisfactorily treated. We report a case of advanced PUC, surgically treated with combined approaches. A 47-year-old man underwent transurethral resection of a urethral lesion with histological evidence of a poorly differentiated squamous cancer of the bulbomembranous urethra. Computed tomography (CT) and bone scans excluded metastatic spread of the disease but showed involvement of both corpora cavernosa (cT3N0M0). A radical surgical approach was advised, but the patient refused this and opted for chemotherapy. After 17 months the patient was referred to our department due to the evidence of a fistula in the scrotal area. CT scan showed bilateral metastatic disease in the inguinal, external iliac, and obturator lymph nodes as well as the involvement of both corpora cavernosa. Additionally, a fistula originating from the right corpus cavernosum extended to the scrotal skin. At this stage, the patient accepted the surgical treatment, consisting of different phases. Phase I: Radical extraperitoneal cystoprostatectomy with iliac-obturator lymph nodes dissection. Phase II: Creation of a urinary diversion through a Bricker ileal conduit. Phase III: Repositioning of the patient in lithotomic position for an overturned Y skin incision, total penectomy, fistula excision, and “en bloc” removal of surgical specimens including the bladder, through the perineal breach. Phase IV: Right inguinal lymphadenectomy. The procedure lasted 9-and-a-half hours, was complication-free, and intraoperative blood loss was 600 mL. The patient was discharged 8 days after surgery. Pathological examination documented a T4N2M0 tumor. The clinical situation was stable during the first 3 months postoperatively but then metastatic spread occurred, not responsive to adjuvant chemotherapy, which led to the patient's death 6 months after surgery. Patients with advanced stage tumors of

  19. Primary healthcare NZ nurses' experiences of advance directives: understanding their potential role.

    PubMed

    Davidson, Raewyn; Banister, Elizabeth; de Vries, Kay

    2013-07-01

    Advance directives are one aspect of advance care planning designed to improve end of life care. The New Zealand Nurses Organisation released their first mission statement in 2010 concerning advance directives suggesting an increase in the use of these. A burgeoning older population, expected to rise over the next few years, places the primary healthcare nurse in a pivotal role to address the challenges in constructing advance directives. While literature supports the role for primary healthcare nurses in promoting advance directives, no research was found on this role in the New Zealand context. This paper presents results of a qualitative study conducted in New Zealand with 13 senior primary healthcare nurses with respect to their knowledge, attitudes, and experiences of advance directives. Results of the analysis revealed a dynamic process involving participants coming to understand their potential role in this area. This process included reflection on personal experience with advance directives; values and ethics related to end of life issues; and professional actions.

  20. Mapping of a gene for autosomal dominant juvenile-onset open-angle glaucoma to chromosome 1 q

    SciTech Connect

    Richards, J.E.; Lichter, P.R.; Torrez, D.; Wong, D.; Johnson, A.T.; Boehnke, M.; Uro, J.L.A. )

    1994-01-01

    A large Caucasian family is presented, in which a juvenile-onset form of open-angle glaucoma is transmitted in an autosomal dominant fashion. Sixteen affected family members were identified from 31 at-risk individuals descended from the affected founder. Affected patients developed high intraocular pressures (sometimes >40 mm Hg) within the first 2 decades of life. Linkage analysis between the disease phenotype and 12 microsatellite repeat markers located on chromosome 1 q gave a maximum lod score of 8.38 at a recombination fraction of zero for marker D1S210. Analysis of recombinant haplotypes suggests a total inclusion region of about 14 cM between markers D1S194 and D1S218 at 1q21-q31. This represents the second juvenile-glaucoma family, in which the disease has been mapped to the long arm of chromosome 1. 57 refs., 2 figs., 3 tabs.

  1. Selective laser trabeculoplasty compared with medical treatment for the initial management of open angle glaucoma or ocular hypertension.

    PubMed

    Pérez, Efraín; Rada, Gabriel; Maul, Eugenio

    2015-12-16

    Selective laser trabeculoplasty is a relatively new therapeutic alternative for the management of open angle glaucoma and ocular hypertension. On the other hand, medical treatment has robust data supporting its efficacy and has progressed in last decades with the introduction of prostaglandin analogues. To compare these two therapies, we searched Epistemonikos database, which is maintained by screening 30 databases, and identified four systematic reviews including four randomized and one non-randomized clinical trial. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded that selective laser trabeculoplasty leads to a smaller absolute intraocular pressure reduction than medical treatment. However, it is not clear if there are differences in treatment success rate or need of additional antiglaucomatous interventions, because the quality of the evidence is low.

  2. Constraining the Lifetime and Opening Angle of Quasars using Fluorescent Lyman α Emission: The Case of Q0420-388

    NASA Astrophysics Data System (ADS)

    Borisova, Elena; Lilly, Simon J.; Cantalupo, Sebastiano; Prochaska, J. Xavier; Rakic, Olivera; Worseck, Gabor

    2016-10-01

    A toy model is developed to understand how the spatial distribution of fluorescent emitters in the vicinity of bright quasars could be affected by the geometry of the quasar bi-conical radiation field and by its lifetime. The model is then applied to the distribution of high-equivalent-width Lyα emitters (with rest-frame equivalent widths above 100 Å, threshold used in, e.g., Trainor & Steidel) identified in a deep narrow-band 36 × 36 arcmin2 image centered on the luminous quasar Q0420-388. These emitters are found near the edge of the field and show some evidence of an azimuthal asymmetry on the sky of the type expected if the quasar is radiating in a bipolar cone. If these sources are being fluorescently illuminated by the quasar, the two most distant objects require a lifetime of at least 15 Myr for an opening angle of 60° or more, increasing to more than 40 Myr if the opening angle is reduced to a minimum of 30°. However, some other expected signatures of boosted fluorescence are not seen at the current survey limits, e.g., a fall off in Lyα brightness, or equivalent width, with distance. Furthermore, to have most of the Lyα emission of the two distant sources to be fluorescently boosted would require the quasar to have been significantly brighter in the past. This suggests that these particular sources may not be fluorescent, invalidating the above lifetime constraints. This would cast doubt on the use of this relatively low equivalent width threshold and thus also on the lifetime analysis in Trainor and Steidel.

  3. A randomised, controlled comparison of latanoprostene bunod and latanoprost 0.005% in the treatment of ocular hypertension and open angle glaucoma: the VOYAGER study

    PubMed Central

    Weinreb, Robert N; Ong, Tuyen; Scassellati Sforzolini, Baldo; Vittitow, Jason L; Singh, Kuldev; Kaufman, Paul L

    2015-01-01

    Aim To assess the efficacy and safety of latanoprostene bunod (LBN) compared with latanoprost 0.005%, and to determine the optimum drug concentration(s) of LBN in reducing intraocular pressure (IOP) in subjects with open angle glaucoma or ocular hypertension. Methods Randomised, investigator-masked, parallel-group, dose-ranging study. Subjects instilled one drop of study medication in the study eye once daily each evening for 28 days and completed five study visits. The primary efficacy endpoint was the reduction in mean diurnal IOP at Day 28. Results Of the 413 subjects randomised (LBN 0.006%, n=82; LBN 0.012%, n=85; LBN 0.024%, n=83; LBN 0.040%, n=81; latanoprost, n=82), 396 subjects completed the study. Efficacy for LBN was dose-dependent reaching a plateau at 0.024%–0.040%. LBN 0.024% led to significantly greater reductions in diurnal IOP compared with latanoprost at the primary endpoint, Day 28 (p=0.005), as well as Days 7 (p=0.033) and 14 (p=0.015). The incidence of adverse events, mostly mild and transient, was numerically higher in the LBN treatment groups compared with the latanoprost group. Hyperaemia was similar across treatments. Conclusions LBN 0.024% dosed once daily was the lower of the two most effective concentrations evaluated, with significantly greater IOP lowering and comparable side effects relative to latanoprost 0.005%. LBN dosed once daily for 28 days was well tolerated. Clinical trial number NCT01223378. PMID:25488946

  4. Glaucoma, Open-Angle

    MedlinePlus

    ... Courier services use: Rockville, MD 20852) 301-451-2020 Research at NEI Office of the Scientific Director ... Eye Disease Education Program Glaucoma Education Program Low Vision Education Program Hispanic/Latino Program Vision and Aging ...

  5. Resin transfer molding for advanced composite primary aircraft structures

    NASA Technical Reports Server (NTRS)

    Markus, Alan; Palmer, Ray

    1991-01-01

    Resin Transfer Molding (RTM) has been identified by Douglas Aircraft Company (DAC) and industry to be one of the promising processes being developed today which can break the cost barrier of implementing composite primary structures into a commercial aircraft production environment. The RTM process developments and scale-up plans Douglas Aircrart will be conducting under the NASA ACT contract are discussed.

  6. Primary electric power generation systems for advanced-technology engines

    NASA Technical Reports Server (NTRS)

    Cronin, M. J.

    1983-01-01

    The advantages of the all electric airplane are discussed. In the all electric airplane the generator is the sole source of electric power; it powers the primary and secondary flight controls, the environmentals, and the landing gear. Five candidates for all electric power systems are discussed and compared. Cost benefits of the all electric airplane are discussed.

  7. Universal Primary Education in Kenya: Advancement and Challenges

    ERIC Educational Resources Information Center

    Ngugi, Margaret; Mumiukha, Catherine; Fedha, Flora; Ndiga, Beatrice

    2015-01-01

    Universalisation of primary education (UPE) has been a global issue since the early sixties, yet several decades later and even in the 21st century, many countries in Sub-Saharan Africa are still grappling with it. Unlike their counterparts in the developed world, its realisation in developing countries has been faced with a myriad of constraints.…

  8. Properties of pattern standard deviation in open-angle glaucoma patients with hemi-optic neuropathy and bi-optic neuropathy

    PubMed Central

    Heo, Dong Won; Kim, Kyoung Nam; Lee, Min Woo; Lee, Sung Bok; Kim, Chang-sik

    2017-01-01

    Purpose To evaluate the properties of pattern standard deviation (PSD) according to localization of the glaucomatous optic neuropathy. Methods We enrolled 242 eyes of 242 patients with primary open-angle glaucoma, with a best-corrected visual acuity ≥ 20/25, and no media opacity. Patients were examined via dilated fundus photography, spectral-domain optical coherence tomography, and Humphrey visual field examination, and divided into those with hemi-optic neuropathy (superior or inferior) and bi-optic neuropathy (both superior and inferior). We assessed the relationship between mean deviation (MD) and PSD. Using broken stick regression analysis, the tipping point was identified, i.e., the point at which MD became significantly associated with a paradoxical reversal of PSD. Results In 91 patients with hemi-optic neuropathy, PSD showed a strong correlation with MD (r = −0.973, β = −0.965, p < 0.001). The difference between MD and PSD (“−MD−PSD”) was constant (mean, −0.32 dB; 95% confidence interval, −2.48~1.84 dB) regardless of visual field defect severity. However, in 151 patients with bi-optic neuropathy, a negative correlation was evident between “−MD−PSD” and MD (r2 = 0.907, p < 0.001). Overall, the MD tipping point was −14.0 dB, which was close to approximately 50% damage of the entire visual field (p < 0.001). Conclusions Although a false decrease of PSD usually begins at approximately 50% visual field damage, in patients with hemi-optic neuropathy, the PSD shows no paradoxical decrease and shows a linear correlation with MD. PMID:28249022

  9. Intraocular Pressure, Central Corneal Thickness, and Prevalence of Open-Angle Glaucoma: The Los Angeles Latino Eye Study

    PubMed Central

    Francis, Brian A.; Varma, Rohit; Chopra, Vikas; Lai, Mei-Ying; Shtir, Corina; Azen, Stanley P.

    2008-01-01

    Purpose To examine the relationship between the prevalence of open-angle glaucoma (OAG) and intraocular pressure (IOP) and the impact of central corneal thickness (CCT) on this relationship. Design Population based cross-sectional study. Methods The study cohort consisted of 5970 participants from the Los Angeles Latino Eye Study (LALES) with no history of glaucoma treatment and with complete ophthalmic examination data. The relationship between the prevalence of OAG and IOP was contrasted across persons with CCT designated as thin, normal or thick. Results Prevalence of OAG was exponentially related to IOP. When stratified by CCT, persons with thin CCT had a significantly higher prevalence of OAG than did those with normal or thick CCT’s at all levels of IOP. Adjusting each IOP individually for CCT did not impact significantly the relationship between the prevalence of OAG and IOP. Conclusions These findings suggest that adjusting for the impact of CCT on IOP by correction algorithms is not necessary in a population analysis of glaucoma prevalence; CCT and other associated corneal properties, however, are important independent risk factors for the prevalence of OAG. PMID:18672218

  10. Prediction of stable tearing of 2024-T3 aluminum alloy using the crack-tip opening angle approach

    NASA Technical Reports Server (NTRS)

    Bakuckas, J. G., Jr.; Newman, J. C., Jr.

    1993-01-01

    In this study, the crack-tip opening angle (CTOA) approach was incorporated into a damage growth finite element program, MADGIC (Micromechanics Analysis and Damage Growth in Composites), and was used to predict stable tearing in a middle-crack tension 2024-T3 aluminum alloy specimen. The MADGIC code is a displacement based finite element program implemented with an incremental elastic-plastic algorithm used to model elastic-plastic behavior and a nodal splitting and nodal force relaxation algorithm used to generate crack surfaces. Predictions of the applied stress as a function of crack extension and applied stress as a function of load-line displacement were in good agreement with experiments and with similar predictions made using an existing finite element program, ZIP2D. In addition, path integrals, namely, the J-integral and T*-integral, were also evaluated and compared with the CTOA approach. There appears to be a weak relationship between the CTOA and the T*-integral evaluated on a specific integration path during crack extension beyond maximum applied stress. This study further verifies that the CTOA can be used as an effective elastic-plastic fracture mechanics parameter to predict crack growth.

  11. Recent advances in treatment of severe primary immunodeficiencies

    PubMed Central

    Gennery, Andrew

    2015-01-01

    Primary immunodeficiencies are rare, inborn errors that result in impaired, disordered or uncontrolled immune responses. Whilst symptomatic and prophylactic treatment is available, hematopoietic stem cell transplantation is an option for many diseases, leading to cure of the immunodeficiency and establishing normal physical and psychological health. Newborn screening for some diseases, whilst improving outcomes, is focusing research on safer and less toxic treatment strategies, which result in durable and sustainable immune function without adverse effects. New conditioning regimens have reduced the risk of hematopoietic stem cell transplantation, and new methods of manipulating stem cell sources should guarantee a donor for almost all patients. Whilst incremental enhancements in transplantation technique have gradually improved survival outcomes over time, some of these new applications are likely to radically alter our approach to treating primary immunodeficiencies. PMID:26918153

  12. Lessons Learned from an Advanced Access Trial Within a Canadian Armed Forces Primary Care Clinic.

    PubMed

    Singh, P Tony

    2017-01-01

    Accessibility is a key element of an effective primary care system. Literature has outlined that primary care practices have successfully employed an advanced access scheduler to improve accessibility to booked appointments and consequently enhance patient experience and outcomes. In 2015, a Canadian Armed Forces (CAF) primary care facility in Ottawa trialed an advanced access scheduler. Based on the unique characteristics of a CAF medical clinic and the patient population, this trial produced six critical lessons, which include maintenance of a stable base of clinicians, correcting rostering mismatches, eliminating appointment backlogs, acquiring required information systems, improved understanding of patient demand and communicating changes effectively. These lessons may be utilized by similar organizations to successfully integrate an advanced access scheduler within their primary care facilities.

  13. Cooperative Research and Development of Primary Surface Recuperator for Advanced Microturbine Systems

    SciTech Connect

    Escola, George

    2007-01-17

    Recuperators have been identified as key components of advanced gas turbines systems that achieve a measure of improvement in operating efficiency and lead the field in achieving very low emissions. Every gas turbine manufacturer that is studying, developing, or commercializing advanced recuperated gas turbine cycles requests that recuperators operate at higher temperature without a reduction in design life and must cost less. The Solar Cooperative Research and Development of Primary Surface Recuperator for Advanced Microturbine Systems Program is directed towards meeting the future requirements of advanced gas turbine systems by the following: (1) The development of advanced alloys that will allow recuperator inlet exhaust gas temperatures to increase without significant cost increase. (2) Further characterization of the creep and oxidation (dry and humid air) properties of nickel alloy foils (less than 0.13 mm thick) to allow the economical use of these materials. (3) Increasing the use of advanced robotic systems and advanced in-process statistical measurement systems.

  14. Clinical evaluation of a trabecular microbypass stent with phacoemulsification in patients with open-angle glaucoma and cataract

    PubMed Central

    Ferguson, Tanner J; Berdahl, John P; Schweitzer, Justin A; Sudhagoni, Ramu G

    2016-01-01

    Purpose To evaluate the safety and efficacy of the iStent trabecular microbypass stent in combination with cataract surgery in patients with open-angle glaucoma (OAG). Methods Retrospective, consecutive case series from October 2012 to December 2015 with no exclusion criteria. The series comprised of 350 eyes with OAG and cataract. Data were collected both preoperatively and postoperatively at day 1 week 1, months 1, 3, 6, 12, 18, and 24. Data included intraocular pressure (IOP), number of glaucoma medications, visual acuity, the incidence of postoperative IOP pressure spikes of greater than ≥15 mmHg at any time point, and need for additional surgery. Results The mean preoperative IOP was 19.13±6.34 mmHg. At 2 years postoperation, mean IOP was 15.17±3.53 mmHg (P<0.0001). The mean number of glaucoma medications was 1.19±1.00 preoperatively and 0.61±0.96 (P<0.0001) at 2 years postoperation. At 1 day postoperatively, 31 eyes (12.4%) experienced an IOP increase of 15 mmHg above their baseline IOP that responded to topical therapy. Two patients required additional tube shunt surgery. Conclusion The insertion of the iStent trabecular microbypass stent in combination with cataract surgery effectively lowers IOP in OAG patients. The magnitude of IOP reduction was more significant in patients with higher preoperative pressure. Medication use was also significantly reduced postoperatively. The safety profile appears favorable with a low rate of IOP spikes and only two eyes (<1%) requiring additional surgery. PMID:27695280

  15. Correlations between Preoperative Angle Parameters and Postoperative Unpredicted Refractive Errors after Cataract Surgery in Open Angle Glaucoma (AOD 500)

    PubMed Central

    Lee, Wonseok; Bae, Hyoung Won; Lee, Si Hyung; Kim, Chan Yun

    2017-01-01

    Purpose To assess the accuracy of intraocular lens (IOL) power prediction for cataract surgery with open angle glaucoma (OAG) and to identify preoperative angle parameters correlated with postoperative unpredicted refractive errors. Materials and Methods This study comprised 45 eyes from 45 OAG subjects and 63 eyes from 63 non-glaucomatous cataract subjects (controls). We investigated differences in preoperative predicted refractive errors and postoperative refractive errors for each group. Preoperative predicted refractive errors were obtained by biometry (IOL-master) and compared to postoperative refractive errors measured by auto-refractometer 2 months postoperatively. Anterior angle parameters were determined using swept source optical coherence tomography. We investigated correlations between preoperative angle parameters [angle open distance (AOD); trabecular iris surface area (TISA); angle recess area (ARA); trabecular iris angle (TIA)] and postoperative unpredicted refractive errors. Results In patients with OAG, significant differences were noted between preoperative predicted and postoperative real refractive errors, with more myopia than predicted. No significant differences were recorded in controls. Angle parameters (AOD, ARA, TISA, and TIA) at the superior and inferior quadrant were significantly correlated with differences between predicted and postoperative refractive errors in OAG patients (-0.321 to -0.408, p<0.05). Superior quadrant AOD 500 was significantly correlated with postoperative refractive differences in multivariate linear regression analysis (β=-2.925, R2=0.404). Conclusion Clinically unpredicted refractive errors after cataract surgery were more common in OAG than in controls. Certain preoperative angle parameters, especially AOD 500 at the superior quadrant, were significantly correlated with these unpredicted errors. PMID:28120576

  16. Albuminuria Is Associated with Open-Angle Glaucoma in Nondiabetic Korean Subjects: A Cross-Sectional Study

    PubMed Central

    Kim, Gyu Ah; Park, Se Hee; Ko, Jaesang; Lee, Si Hyung; Bae, Hyoung Won; Seong, Gong Je; Kim, Chan Yun

    2016-01-01

    Objective Systemic vascular dysfunction has been suggested to contribute to glaucomatous damage. Albuminuria is a surrogate marker of endothelial injury, including vessels. However, their relationship is not well understood. This study aimed to investigate the association between albuminuria and the prevalence of open-angle glaucoma (OAG) in nondiabetic subjects. Methods We conducted a cross-sectional study of 4186 nondiabetic participants aged 19 years or older from the 2011–2012 Korea National Health and Nutrition Examination Survey. OAG was defined based on the criteria of the International Society for Geographic and Epidemiologic Ophthalmology. Urinary albumin excretion was assessed by the urinary albumin-to-creatinine ratio (UACR). A multivariate logistic regression analysis was performed to evaluate the relationship between albuminuria and OAG. Results Among the subjects, 124 had OAG. The weighted prevalences of microalbuminuria (UACR of 30–299 mg/g creatinine [Cr]) and macroalbuminuria (UACR ≥ 300 mg/g Cr) were 3.2 ± 0.3% and 0.4 ± 0.1%, respectively. The percentages of OAG increased in accordance with increasing UACR tertiles. Compared with subjects in the lower UACR tertile, those in the upper tertile showed an increased prevalence of OAG (odds ratio, 1.963; 95% confidence interval 1.072–3.595, P = 0.029) after adjusting for demographic factors, laboratory parameters, kidney function, and intraocular pressure. Furthermore, even after excluding 155 subjects with microalbuminuria and 19 subjects with macroalbuminuria, a positive association persisted between the upper UACR tertile (low-grade albuminuria) and an increased prevalence of OAG (odds ratio, 2.170; 95% confidence interval, 1.174–4.010, P = 0.014). Conclusion Albuminuria, even low-grade, was significantly associated with OAG in nondiabetic subjects. This result implies the role of vascular endothelial dysfunction in the pathogenic mechanism of OAG and suggests that careful monitoring of

  17. Crack-tip-opening angle measurements and crack tunneling under stable tearing in thin sheet 2024-T3 aluminum alloy

    NASA Technical Reports Server (NTRS)

    Dawicke, D. S.; Sutton, M. A.

    1993-01-01

    The stable tearing behavior of thin sheets 2024-T3 aluminum alloy was studied for middle crack tension specimens having initial cracks that were: flat cracks (low fatigue stress) and 45 degrees through-thickness slant cracks (high fatigue stress). The critical crack-tip-opening angle (CTOA) values during stable tearing were measured by two independent methods, optical microscopy and digital image correlation. Results from the two methods agreed well. The CTOA measurements and observations of the fracture surfaces showed that the initial stable tearing behavior of low and high fatigue stress tests is significantly different. The cracks in the low fatigue stress tests underwent a transition from flat-to-slant crack growth, during which the CTOA values were high and significant crack tunneling occurred. After crack growth equal to about the thickness, CTOA reached a constant value of 6 deg and after crack growth equal to about twice the thickness, crack tunneling stabilized. The initial high CTOA values, in the low fatigue crack tests, coincided with large three-dimensional crack front shape changes due to a variation in the through-thickness crack tip constraint. The cracks in the high fatigue stress tests reach the same constant CTOA value after crack growth equal to about the thickness, but produced only a slightly higher CTOA value during initial crack growth. For crack growth on the 45 degree slant, the crack front and local field variables are still highly three-dimensional. However, the constant CTOA values and stable crack front shape may allow the process to be approximated with two-dimensional models.

  18. Primary radiation therapy for locally advanced breast cancer

    SciTech Connect

    Sheldon, T.; Hayes, D.F.; Cady, B.; Parker, L.; Osteen, R.; Silver, B.; Recht, A.; Come, S.; Henderson, I.C.; Harris, J.R.

    1987-09-15

    The optimal local-regional treatment for patients with Stage III breast cancer has not been determined. To evaluate the effectiveness of radiation therapy as local treatment for such patients, the results of 192 patients (five with bilateral disease) treated with radiation therapy without mastectomy between July 1, 1968 and December 31, 1981 were reviewed. Excisional biopsy (gross tumor removal) was performed in only 54 of the 197 breasts. Patients typically received 4500 to 5000 cGy in 5 weeks to the breast and draining lymph nodes; a local boost to areas of gross disease was delivered to 157 patients. Multi-agent chemotherapy was given to 53 patients. The median follow-up was 65 months. The actuarial probability of survival for the entire group was 41% at 5 years and 23% at 10 years. The probability of relapse-free survival (RFS) was 30% at 5 years and 19% at 10 years. The addition of multi-agent chemotherapy was associated with a significantly improved 5-year RFS (40% versus 26%, P = 0.02). The 5-year survival rate was 51% for patients who received adjuvant multi-agent chemotherapy and 38% for patients who did not (P = 0.16). The actuarial rate of local-regional tumor control (not censored for distant failure) for all patients was 73% at 5 years and 68% at ten years, and the crude incidence of local-regional control was 78%. Local-regional tumor control was principally influenced by radiation dose. Patients who received 6000 cGy or greater to the primary site had a better 5-year rate of control in the breast than did patients who received less than 6000 cGy (83% versus 70%, P = 0.06). Significant complications were seen in 15 patients (8%); these included moderate or severe arm edema in six patients and brachial plexopathy in four patients. Cosmetic results at last evaluation were excellent or good in 56% of evaluable patients, fair in 25%, and poor in 19%.

  19. Trends in Utilization of Ancillary Glaucoma Tests for Patients with Open-Angle Glaucoma from 2001 to 2009

    PubMed Central

    Stein, Joshua D.; Talwar, Nidhi; Laverne, Alejandra; Nan, Bin; Lichter, Paul R.

    2011-01-01

    Purpose To assess trends in the use of ancillary diagnostic tests in the evaluation of patients with open-angle glaucoma (OAG) and glaucoma suspects over the past decade. Design Retrospective longitudinal cohort analysis. Participants 169,917 individuals with OAG and 395,721 with suspected glaucoma age ≥40 enrolled in a national United States managed care network between 2001–2009. Methods Claims data were analyzed to assess trends in visual field (VF) testing, fundus photography (FP), and other ocular imaging (OOI) testing for patients with OAG or suspected glaucoma in 2001–2009. Repeated measures logistic regression was performed to identify differences in the odds of undergoing these procedures in 2001, 2005, and 2009 and whether differences exist for patients under the exclusive care of optometrists versus ophthalmologists. Main Outcome Measures Odds and annual probabilities of undergoing VF testing, FP, and OOI for OAG from 2001–2009. Results For patients with OAG, the odds of undergoing VF testing decreased by 36% from 2001 to 2005, 12% from 2005 to 2009, and 44% from 2001 to 2009. By comparison, the odds of having OOI increased by 100% from 2001 to 2005, 24% from 2005 to 2009, and 147% from 2001 to 2009. Probabilities of undergoing FP were relatively low (13–25%) for both provider types and remained fairly steady over the decade. For patients cared for exclusively by optometrists, the probability of VF testing decreased from 66% in 2001 to 44% in 2009. Among those seen exclusively by ophthalmologists, the probability of VF testing decreased from 65% in 2001 to 51% in 2009. The probability of undergoing OOI increased from 26% in 2001 to 47% in 2009 for patients of optometrists and from 30% in 2001 to 46% in 2009 for patients of ophthalmologists. By 2008, patients with OAG receiving care exclusively by optometrists had a higher probability of undergoing OOI than VF testing. Conclusion During 2001–2009 OOI rose dramatically whereas VF testing

  20. Associations of sleep duration with open angle glaucoma in the Korea national health and nutrition examination survey

    PubMed Central

    Lee, Jin-Ah; Han, Kyungdo; Min, Jung Ah; Choi, Jin A

    2016-01-01

    Abstract The aim of this study is to investigate the relationship between sleep duration and glaucoma, stratified by obesity status. This study was conducted using data from the Korean National Health and Nutrition Examination Survey V 2010 to 2012. Open-angle glaucoma was diagnosed according to the International Society of Geographical and Epidemiological Ophthalmology criteria. Subjects were divided into subgroups based on those who were overweight (body mass index ≥25 kg/m2 or <25 kg/m2) or with abdominal obesity (based on waist circumference). Multiple logistic regression analysis was done to estimate the magnitude of the association between sleep duration (<7 h, 7–<9, or ≥9 hours) and prevalence of glaucoma in the total population and in the subgroups. Individuals who slept <5 hours per night had the highest prevalence of glaucoma (5.55 ± 1.09%), followed by those who slept ≥9 hours per night (4.56 ± 0.10%), and then by those who slept 5 to <6 hours per night (4.15 ± 0.68%), which revealed a U-shaped pattern (P for trend = 0.072). Among overweight individuals, subjects who slept <7 hours and those who slept ≥9 hours were significantly more likely to have glaucoma compared with subjects who slept 7 to <9 hours after adjusting for survey year, age, sex, smoking, drinking, exercise, education level, household income, hypertension, intraocular pressure, stress, and depression (odds ratio, 2.41; 95% confidence interval, 1.14–5.03). Unlike for overweight individuals, sleep duration in nonoverweight individuals was not statistically significantly associated with glaucoma. Our results reveal a U-shaped association between sleep duration and the prevalence of glaucoma. An effect of sleep duration on glaucoma was present in the subgroup of overweight patients. PMID:28033268

  1. Associations of sleep duration with open angle glaucoma in the Korea national health and nutrition examination survey.

    PubMed

    Lee, Jin-Ah; Han, Kyungdo; Min, Jung Ah; Choi, Jin A

    2016-12-01

    The aim of this study is to investigate the relationship between sleep duration and glaucoma, stratified by obesity status.This study was conducted using data from the Korean National Health and Nutrition Examination Survey V 2010 to 2012. Open-angle glaucoma was diagnosed according to the International Society of Geographical and Epidemiological Ophthalmology criteria. Subjects were divided into subgroups based on those who were overweight (body mass index ≥25 kg/m or <25 kg/m) or with abdominal obesity (based on waist circumference). Multiple logistic regression analysis was done to estimate the magnitude of the association between sleep duration (<7 h, 7-<9, or ≥9 hours) and prevalence of glaucoma in the total population and in the subgroups.Individuals who slept <5 hours per night had the highest prevalence of glaucoma (5.55 ± 1.09%), followed by those who slept ≥9 hours per night (4.56 ± 0.10%), and then by those who slept 5 to <6 hours per night (4.15 ± 0.68%), which revealed a U-shaped pattern (P for trend = 0.072). Among overweight individuals, subjects who slept <7 hours and those who slept ≥9 hours were significantly more likely to have glaucoma compared with subjects who slept 7 to <9 hours after adjusting for survey year, age, sex, smoking, drinking, exercise, education level, household income, hypertension, intraocular pressure, stress, and depression (odds ratio, 2.41; 95% confidence interval, 1.14-5.03). Unlike for overweight individuals, sleep duration in nonoverweight individuals was not statistically significantly associated with glaucoma.Our results reveal a U-shaped association between sleep duration and the prevalence of glaucoma. An effect of sleep duration on glaucoma was present in the subgroup of overweight patients.

  2. Association of Myopic Deformation of Optic Disc with Visual Field Progression in Paired Eyes with Open-Angle Glaucoma

    PubMed Central

    Hangai, Masanori; Ishikawa, Makoto; Yoshitomi, Takeshi

    2017-01-01

    Purpose The influence of myopia on glaucoma progression remains unknown, possibly because of the multifactorial nature of glaucoma and difficulty in assessing a solo contribution of myopia. The purpose of this study is to investigate the association of myopia with visual field (VF) progression in glaucoma using a paired-eye design to minimize the influence of confounding systemic factors that are diverse among individuals. Methods This retrospective study evaluated 144 eyes of 72 subjects with open-angle glaucoma, with similar intra-ocular pressure between paired eyes, spherical equivalent (SE) ≤ -2 diopter (D), and axial length ≥ 24 mm. Paired eyes with faster and slower VF progression were grouped separately, according to the global VF progression rate assessed by automated pointwise linear regression analysis. The SE, axial length, tilt ratio and torsion angle of optic discs, Bruch’s membrane (BM) opening area, and gamma zone parapapillary atrophy (PPA) width were compared between the two groups. Factors associated with faster VF progression were determined by logistic regression analysis. Results The mean follow-up duration was 8.9 ± 4.4 years. The mean value of SE and axial length were -6.31 ± 1.88 D and 26.05 ± 1.12 mm, respectively. The mean global visual field progression rate was -0.32 ± 0.38 dB/y. Tilt ratio, BM opening area, and gamma zone PPA width were significantly greater in the eyes with faster VF progression than those with slower progression. In multivariate analysis, these factors were significantly associated with faster VF progression (all P < 0.05), while SE and axial length were not associated with it. Conclusion In myopic glaucoma subjects, tilt of the optic disc and temporal shifting and enlargement of the BM opening were associated with faster rate of VF progression between paired eyes. This suggests that myopia influences VF progression in glaucomatous eyes via optic disc deformations rather than via refractive error itself

  3. Prospective, randomized study of one, two, or three trabecular bypass stents in open-angle glaucoma subjects on topical hypotensive medication

    PubMed Central

    Katz, L Jay; Erb, Carl; Carceller, Guillamet Amadeu; Fea, Antonio M; Voskanyan, Lilit; Wells, Jeffrey M; Giamporcaro, Jane Ellen

    2015-01-01

    Purpose To assess the safety and efficacy of one, two, or three trabecular microbypass stents in eyes with primary open-angle glaucoma (OAG) not controlled on ocular hypotensive medication. A total of 119 subjects were followed for 18 months postoperatively. Materials and methods Subjects with medicated intraocular pressure (IOP) 18–30 mmHg and postmedication-washout baseline IOP 22–38 mmHg were randomized to implantation of one, two, or three stents. Ocular hypotensive medication was to be used if postoperative IOP exceeded 18 mmHg. Results A total of 38 subjects were implanted with one stent, 41 subjects with two stents, and 40 subjects with three stents. Both month 12 IOP reduction ≥20% without ocular hypotensive medication vs baseline unmedicated IOP and month 12 unmedicated IOP ≤18 mmHg were achieved by 89.2%, 90.2%, and 92.1% of one-, two-, and three-stent eyes, respectively. Furthermore, 64.9%, 85.4%, and 92.1% of the three respective groups achieved unmedicated IOP ≤15 mmHg. Over the 18-month follow-up period, medication was required in seven one-stent subjects, four two-stent subjects, and three three-stent subjects. At 18 months, mean unmedicated IOP was 15.9±0.9 mmHg in one-stent subjects, 14.1±1.0 mmHg in two-stent subjects, and 12.2±1.1 mmHg in three-stent subjects. Month 18 IOP reduction was significantly greater (P<0.001) with implantation of each additional stent, with mean differences in reduction of 1.84 mmHg (95% confidence interval 0.96–2.73) for three-stent vs two-stent groups and 1.73 mmHg (95% confidence interval 0.83–2.64) for two-stent vs one-stent groups. Adverse events through 18 months were limited to cataract progression with best-corrected visual acuity loss and subsequent cataract surgery. Conclusion In this series, implantation of each additional stent resulted in significantly greater IOP reduction with reduced medication use. Titratability of stents as a sole procedure was shown to be effective and safe, with

  4. Modeling a decrease in hydraulic losses during turbulent flow in a U-bend channel with a circular cavern with a large opening angle

    NASA Astrophysics Data System (ADS)

    Isaev, S. A.; Kalinin, E. I.; Tereshkin, A. A.; Usachov, A. E.

    2015-03-01

    The Reynolds equations for incompressible viscous fluid, closed using the Menter shear-stress-transfer model modified with allowance for the curvature of flow lines, have been numerically solved using multiblock computational technologies. The obtained solution has been used to calculate the turbulent flow in a U-bend channel containing a circular cavern with a variable opening angle. Predictions based on the results of numerical simulations agree well with the experimental data of Savelsberg and Castro at moderate cavern opening angles. It is established that hydraulic losses in a U-bend channel with completely open cavern are significantly (by ˜25%) decreased as compared to those in a smooth channel at Re = 105.

  5. Advanced composite structural concepts and material technologies for primary aircraft structures

    NASA Technical Reports Server (NTRS)

    Jackson, Anthony

    1991-01-01

    Structural weight savings using advanced composites have been demonstrated for many years. Most military aircraft today use these materials extensively and Europe has taken the lead in their use in commercial aircraft primary structures. A major inhibiter to the use of advanced composites in the United States is cost. Material costs are high and will remain high relative to aluminum. The key therefore lies in the significant reduction in fabrication and assembly costs. The largest cost in most structures today is assembly. As part of the NASA Advanced Composite Technology Program, Lockheed Aeronautical Systems Company has a contract to explore and develop advanced structural and manufacturing concepts using advanced composites for transport aircraft. Wing and fuselage concepts and related trade studies are discussed. These concepts are intended to lower cost and weight through the use of innovative material forms, processes, structural configurations and minimization of parts. The approach to the trade studies and the downselect to the primary wing and fuselage concepts is detailed. The expectations for the development of these concepts is reviewed.

  6. Advanced Practice Registered Nurses: Gateway to Screening for Bipolar Disorder in Primary Care

    PubMed Central

    Kriebel-Gasparro, Ann Marie

    2016-01-01

    Objective: The goal of this mixed methods descriptive study was to explore Advanced Practice Registered Nurses’ (APRNs’) knowledge of bipolar disorder (BPD) and their perceptions of facilitators and barriers to screening patients with known depression for BPD. Methods: A mixed method study design using surveys on BPD knowledge and screening practices as well as focus group data collection method for facilitators and barriers to screening. Results: 89 APRNs completed the survey and 12 APRNs participated in the focus groups. APRNs in any practice setting had low knowledge scores of BPD. No significant differences in screening for BPD for primary and non primary care APRNs. Qualitative findings revealed screening relates to tool availability; time, unsure of when to screen, fear of sigma, symptoms knowledge of BPD, accessible referral system, personal experiences with BPD, and therapeutic relationships with patients. Conclusion: Misdiagnosis of BPD as unipolar depression is common in primary care settings, leading to a long lag time to optimal diagnosis and treatment. The wait time to diagnosis and treatment could be reduced if APRNs in primary care settings screen patients with a diagnosis of depression by using validated screening tools. These results can inform APRN practice and further research on the effectiveness of screening for reducing the morbidity and mortality of BPDs in primary care settings; underscores the need for integration of mental health care into primary care as well as the need for more APRN education on the diagnosis and management of bipolar disorders. PMID:27347256

  7. Advanced primary pulmonary lymphoepithelioma-like carcinoma: clinical manifestations, treatment, and outcome

    PubMed Central

    Lin, Chun-Yu; Chen, Ying-Jen; Hsieh, Meng-Heng; Wang, Chih-Wei

    2017-01-01

    Background Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is rare, with better clinical outcomes than other lung cancers. However, reports on advanced LELC characteristics and prognosis are lacking. Methods This retrospective study included adults diagnosed with advanced LELC (at least stage IIIA) between January 2003 and December 2015. Clinical characteristics, treatment modalities, and outcomes were recorded. Results Study population comprised 23 patients with a mean age of 63.7±10.6 years. The Eastern Cooperative Oncology Group status on diagnosis was 0 in five patients and 1 in the others. Most patients received multimodality treatment and all received cisplatin-based chemotherapy. Median follow-up duration was 28.8 months. The median progression free survival (PFS) was 14.6 months in patients received palliative chemotherapy. There were nine (39.1%) deaths. The median overall survival (OS) was not achieved. Until July 31, 2016, median OS was 54.1 months for stage IIIB and 27.6 months for stage IV. There was no significant difference in OS among all stages. No prognostic factors were found. Conclusions Advanced LELC responded well to cisplatin-based chemotherapy and/or radiotherapy. Main tumor resection is probably beneficial for advanced LELC. Long-term survival is possible for advanced LELC after multimodality treatment. PMID:28203414

  8. Simulation of the Turbulent air Flow Over a Circular Cavity with a Variable Opening Angle in an U-Shaped Channel

    NASA Astrophysics Data System (ADS)

    Isaev, S. A.; Baranov, P. A.; Usachov, A. E.; Zhukova, Yu. V.; Vysotskaya, A. A.; Malyshkin, D. A.

    2015-07-01

    A numerical investigation of the influence of the opening angle of a circular cavity in an U-shaped channel and the Reynolds number of a fluid fl ow in this channel on the local characteristics and turbulence of this fl ow has been performed based on the solution of the Reynolds equations, closed by the old and new Menter shear-stress transfer models and two variants of this model accounting for the curvature of streamlines, with the use of multiblock computational technologies realized in the VP2/3 package. The results of calculations were compared with each other and with experimental data of I. Castro and R. Savelsberg. This comparison has shown that the best agreement between the numerical predictions and experiments is obtained in the case where calculations are performed within the framework of the Leshtsiner-Rody-Isaev approach with correction for the eddy viscosity of the fluid fl ow. It was established that with increase in the Reynolds number and in the opening angle of the cavity the circulation flow in the near-wall layer of the vortex trapped in the cavity intensifies at a practically constant vorticity in the core of the vortex.

  9. Advancing general practice nursing in Australia: roles and responsibilities of primary healthcare organisations.

    PubMed

    Lane, Riki; Halcomb, Elizabeth; McKenna, Lisa; Zwar, Nicholas; Naccarella, Lucio; Davies, Gawaine Powell; Russell, Grant

    2016-04-21

    Objectives Given increased numbers and enhanced responsibilities of Australian general practice nurses, we aimed to delineate appropriate roles for primary health care organisations (PHCOs) to support this workforce.Methods A two-round online Delphi consensus process was undertaken between January and June 2012, informed by literature review and key informant interviews. Participants were purposively selected and included decision makers from government and professional organisations, educators, researchers and clinicians from five Australian states and territoriesResults Of 56 invited respondents, 35 (62%) and 31 (55%) responded to the first and second invitation respectively. Participants reached consensus on five key roles for PHCOs in optimising nursing in general practice: (1) matching workforce size and skills to population needs; (2) facilitating leadership opportunities; (3) providing education and educational access; (4) facilitating integration of general practice with other primary care services to support interdisciplinary care; and (5) promoting advanced nursing roles. National concerns, such as limited opportunities for postgraduate education and career progression, were deemed best addressed by national nursing organisations, universities and peak bodies.Conclusions Advancement of nursing in general practice requires system-level support from a range of organisations. PHCOs play a significant role in education and leadership development for nurses and linking national nursing organisations with general practices.What is known about the topic? The role of nurses in Australian general practice has grown in the last decade, yet they face limited career pathways and opportunities for career advancement. Some nations have forged interprofessional primary care teams that use nurses' skills to the full extent of their scope of practice. PHCOs have played important roles in the development of general practice nursing in Australia and internationally

  10. Advanced training for primary care and general practice nurses: enablers and outcomes of postgraduate education.

    PubMed

    Hallinan, Christine M; Hegarty, Kelsey L

    2016-01-01

    The aims of the present study were to understand enablers to participation in postgraduate education for primary care nurses (PCNs), and to explore how postgraduate education has advanced their nursing practice. Cross-sectional questionnaires were mailed out in April 2012 to current and past students undertaking postgraduate studies in primary care nursing at The University of Melbourne, Victoria, Australia. Questionnaires were returned by 100 out of 243 nurses (response rate 41%). Ninety-one per cent (91/100) of the respondents were first registered as nurses in Australia. Fifty-seven per cent were hospital trained and 43% were university educated to attain their initial nurse qualification. The respondents reported opportunities to expand scope of practice (99%; 97/98), improve clinical practice (98%; 97/99), increase work satisfaction (93%; 91/98) and increase practice autonomy (92%; 89/97) as factors that most influenced participation in postgraduate education in primary care nursing. Major enablers for postgraduate studies were scholarship access (75%; 71/95) and access to distance education (74%; 72/98). Many respondents reported an increased scope of practice (98%; 95/97) and increased job satisfaction (71%; 70/98) as an education outcome. Only 29% (28/97) cited an increase in pay-rate as an outcome. Of the 73 PCNs currently working in general practice, many anticipated an increase in time spent on the preparation of chronic disease management plans (63%; 45/72), multidisciplinary care plans (56%; 40/72) and adult health checks (56%; 40/72) in the preceding 12 months. Recommendations emerging from findings include: (1) increased access to scholarships for nurses undertaking postgraduate education in primary care nursing is imperative; (2) alternative modes of course delivery need to be embedded in primary care nursing education; (3) the development of Australian primary care policy, including policy on funding models, needs to more accurately reflect the

  11. Endothelial P-selectin expression is reduced in advanced primary melanoma and melanoma metastasis.

    PubMed Central

    Nooijen, P. T.; Westphal, J. R.; Eggermont, A. M.; Schalkwijk, C.; Max, R.; de Waal, R. M.; Ruiter, D. J.

    1998-01-01

    Some malignant tumors induce a cellular immune response that results in the formation of an inflammatory infiltrate and subsequent tumor regression. The infiltrating leukocytes extravasate from the bloodstream after binding to adhesion receptors on the surface of the endothelium. One of these receptors is the P-selectin molecule (CD62P) that is constitutively present on normal capillaries. We observed that P-selectin expression is absent from the microvasculature in advanced primary melanoma and in melanoma metastasis in contrast to benign melanocytic lesions where P-selectin expression was identical to that in normal skin. We suggest that one of the mechanisms by which advanced melanoma lesions evade inflammatory regression operates via a decrease of endothelial P-selectin expression. Images Figure 1 PMID:9502409

  12. HST Multicolor (255-1042 nm) Photometry of Saturn's Main Rings. 1; Radial Profiles, Phase and Opening Angle Variations, and Regional Spectra

    NASA Technical Reports Server (NTRS)

    Cuzzi, Jeffrey N.; French, Richard G.; Dones, Luke; DeVincenzi, Donald (Technical Monitor)

    2001-01-01

    The main rings of Saturn were observed with the Planetary Camera of the WFPC2 instrument on the Hubble Space Telescope (HST) from September 1996 to August 2000 as the'ring opening angle to Earth and Sun increased from 4 deg to 24 deg, with a spread of phase angles between 0.3 deg and 6 deg at each opening angle. The rings were routinely observed in the five HST wideband UBVRI filters (F336W, F439W, F555W, F675W, and F814W) and occasionally in the F255W, F785LP, and F1042M filters. The emphasis in this series of papers will be on radial color (implying compositional) variations. In this first paper we describe the analysis technique and calibration procedure, note revisions in a previously published Voyager ring color data analysis, and present new results based on over 100 HST images. In the 300-600 nm spectral range where the rings are red, the 555nm/336nm ratio increases by about 14% as the phase angle increases from 0.3 deg to 6 deg. This effect, never reported previously for the rings, is significantly larger than the phase reddening which characterizes other icy objects, primarily because of the redness of the rings. However, there is no discernible tendency for color to vary with ring opening angle at a given phase angle, and there is no phase variation of color where the spectrum is flat. We infer from this combination of facts that multiple intraparticle scattering, either in a regolith or between facets of an unusually rough surface, is important in these geometries, but that multiple interparticle scattering in a vertically extended layer is not. Voyager color ratios at a phase angle of 14 deg are compatible with this trend, but calibration uncertainties prevent their use in quantitative modeling. Overall ring-average spectra are compatible with those of earlier work within calibration uncertainties, but ring spectra vary noticeably with region. We refine and subdivide the regions previously defined by others. The variation seen between radial profiles of

  13. Thermal Analysis of the Advanced Technology Large Aperture Space Telescope (ATLAST) 8 Meter Primary Mirror

    NASA Technical Reports Server (NTRS)

    Hornsby, Linda; Stahl, H. Philip; Hopkins, Randall C.

    2010-01-01

    The Advanced Technology Large Aperture Space Telescope (ATLAST) preliminary design concept consists of an 8 meter diameter monolithic primary mirror enclosed in an insulated, optical tube with stray light baffles and a sunshade. ATLAST will be placed in orbit about the Sun-Earth L2 and will experience constant exposure to the sun. The insulation on the optical tube and sunshade serve to cold bias the telescope which helps to minimize thermal gradients. The primary mirror will be maintained at 280K with an active thermal control system. The geometric model of the primary mirror, optical tube, sun baffles, and sunshade was developed using Thermal Desktop(R) SINDA/FLUINT(R) was used for the thermal analysis and the radiation environment was analyzed using RADCAD(R). A XX node model was executed in order to characterize the static performance and thermal stability of the mirror during maneuvers. This is important because long exposure observations, such as extra-solar terrestrial planet finding and characterization, require a very stable observatory wave front. Steady state thermal analyses served to predict mirror temperatures for several different sun angles. Transient analyses were performed in order to predict thermal time constant of the primary mirror for a 20 degree slew or 30 degree roll maneuver. This paper describes the thermal model and provides details of the geometry, thermo-optical properties, and the environment which influences the thermal performance. All assumptions that were used in the analysis are also documented. Parametric analyses are summarized for design parameters including primary mirror coatings and sunshade configuration. Estimates of mirror heater power requirements are reported. The thermal model demonstrates results for the primary mirror heated from the back side and edges using a heater system with multiple independently controlled zones.

  14. Fine mapping of juvenile primary open angle glaucoma (POAG) on 1q21-q31 and exculsion of adult-POAG from the respective region

    SciTech Connect

    Child, A.; Sarfarazi, M.; Crick, R.P.

    1994-09-01

    Juvenile POAG is an autosomal dominant eye disorder which has recently been mapped to 1q21-q24, in a region of 14-23 cM. We report here linkage analysis of 9 microsatellite repeat markers spanning this region in families from England, Scotland and Sardinia. We have observed no recombinants with D1S433 (Z=2.86) and obtained looser linkage with D1S196 ({theta}=0.03; Z=6.38), D1S431 ({theta}=0.14; Z=2.74), D1S210 ({theta}=0.06; Z=1.32), D1S452 ({theta}=0.18; Z=0.729) and D1S242 ({theta}=0.08; Z=2.29). In one family, a critical recombinant in an affected individual localizes the J-POAG locus between D1S452 and D1S242 in a 3 cM region. However, other recombinants in two normal individuals from different families suggests that J-POAG may be localized in a 1 cM distance between D1S433 and D1S431. These unaffected individuals have well passed the age-of-onset in their respective pedigrees. This result suggests that either these two recombinant individuals are gene carriers (i.e., non-penetrants) or there are more than one gene in this region causing the same disease. The possibility of the latter is less likely, since in addition to a total of 4 non-penetrant individuals in our panel, other such cases have also been reported previously. This in turn suggests that the precentage of non-penetrant cases in J-POAG may be considerably higher than it was previously appreciated. Study of 14 families with adult-onset POAG revealed no segregation with the above-mentioned linked microsatellite markers. Our findings confirm, for the first time, that adult-POAG is genetically distinct from the J-POAG. Genetic linkage study of adult families with additional STRPs is currently in progress.

  15. GPs’ views on managing advanced chronic kidney disease in primary care: a qualitative study

    PubMed Central

    Tonkin-Crine, Sarah; Santer, Miriam; Leydon, Geraldine M; Murtagh, Fliss EM; Farrington, Ken; Caskey, Fergus; Rayner, Hugh; Roderick, Paul

    2015-01-01

    Background Chronic kidney disease (CKD) has become a significant part of the GP’s workload since the introduction of the National Institute for Health and Care Excellence guidelines in 2008. Patients with advanced CKD (stages G4 and G5) often have comorbidities, varied disease progression, and are likely to be older. GPs may experience difficulties with management decisions for patients with advanced CKD, including when to refer to nephrology. Aim To explore GPs’ views of managing patients with advanced CKD and referral to secondary care. Design and setting Qualitative study with GPs in four areas of England: London, Bristol, Birmingham, and Stevenage. Method Semi-structured interviews with 19 GPs. Transcribed interviews were thematically analysed. Results GPs had little experience of managing patients with advanced CKD, including those on dialysis or having conservative care (treatment without dialysis or a transplant), and welcomed guidance. Some GPs referred patients based on renal function alone and some used wider criteria including age and multimorbidity. GPs reported a tension between national guidance and local advice, and some had learnt from experience that patients were discharged back to primary care. GPs with more experience of managing CKD referred patients later, or sometimes not at all, if there were no additional problems and if dialysis was seen as not in the patient’s interests. Conclusion GPs want guidance on managing older patients with advanced CKD and comorbidities, which better incorporates agreement between local and national recommendations to clarify referral criteria. GPs are not generally aware of conservative care programmes provided by renal units, however, they appear happy to contribute to such care or alternatively, lead conservative management with input from renal teams. PMID:26120137

  16. Recent advances in the diagnosis and treatment of primary biliary cholangitis

    PubMed Central

    Huang, Ying-Qiu

    2016-01-01

    Primary biliary cholangitis (PBC), formerly referred to as primary biliary cirrhosis, is an infrequent progressive intrahepatic cholestatic autoimmune illness that can evolve into hepatic fibrosis, hepatic cirrhosis, hepatic failure, and, in some cases, hepatocellular carcinoma. The disease itself is characterized by T-lymphocyte-mediated chronic non-suppurative destructive cholangitis and elevated serum levels of extremely specific anti-mitochondrial autoantibodies (AMAs). In this article, we will not only review epidemiology, risk factors, natural history, predictive scores, radiologic approaches (e.g., acoustic radiation force impulse imaging, vibration controlled transient elastography, and magnetic resonance elastography), clinical features, serological characteristics covering biochemical markers, immunoglobulins, infections markers, biomarkers, predictive fibrosis marker, specific antibodies (including AMAs such as AMA-M2), anti-nuclear autoantibodies [such as anti-multiple nuclear dot autoantibodies (anti-sp100, PML, NDP52, anti-sp140), anti-rim-like/membranous anti-nuclear autoantibodies (anti-gp210, anti-p62), anti-centromere autoantibodies, and some of the novel autoantibodies], histopathological characteristics of PBC, diagnostic advances, and anti-diastole of PBC. Furthermore, this review emphasizes the recent advances in research of PBC in terms of therapies, including ursodeoxycholic acid, budesonide, methotrexate, obeticholic acid, cyclosporine A, fibrates such as bezafibrate and fenofibrate, rituximab, mesenchymal stem cells transplant, and hepatic transplant. Currently, hepatic transplant remains the only optimal choice with acknowledged treatment efficiency for end-stage PBC patients. PMID:27957241

  17. Recent advances in transplantation for primary immune deficiency diseases: a comprehensive review.

    PubMed

    de la Morena, M Teresa; Nelson, Robert P

    2014-04-01

    Hematopoietic cell transplantation (HCT) is a curative therapeutic option for severe combined immunodeficiency (SCID), a group of diseases which otherwise carry life expectancies that are of limited duration and quality. Survival following HCT for SCID has improved from approximately 23 to 91 % over the last 40 years. Success with SCID prompted efforts to apply HCT to the therapeutic challenge of well over 20 molecularly defined primary immune deficiency diseases (PID). Such success is due to both early recognition of PIDs and advances in the field of transplantation. Such advances include high-resolution HLA DNA donor-recipient matching, expansion of donor sources, better tolerated conditioning, new antibiotics, and wider availability. International collaborative efforts have provided patients and caregivers information that permit better treatment decisions now, and direct clinicians and investigators to ensure progress in the future. Pioneers in screening for SCID have taken steps to correct the fundamental challenge to successful treatment, which is the rapid discovery and characterization of cases and offering the transplant option to an affected child early in life; blood spot testing for T and B cell receptor quantification is now available to a growing fraction of newborns. Organizations including the Primary Immune Deficiency Treatment Consortium in the USA, The European Society for Primary Immunodeficiency, the European Group for Blood and Marrow Transplantation, the Pediatric Blood and Marrow Transplant Consortium, the United States Immunodeficiency Network, the Immune Deficiency Foundation, and the Jeffrey Modell Foundation are contributing mightily to increase awareness and standardize optimal utilization to the benefit of patients. This review will update the allergist-immunologist concerning disease presentations, indications for transplantation, methodologies, conditioning regimens, and clinical outcomes for patients with PID for which timely HCT is

  18. Stability of the HER2 gene after primary chemotherapy in advanced breast cancer.

    PubMed

    Varga, Zsuzsanna; Caduff, Rosmarie; Pestalozzi, Bernhard

    2005-02-01

    We investigated whether alterations of the Her2 gene could be detected in breast cancer samples following primary chemotherapy in advanced breast cancer. The prospective study involved 23 patients with stage-II, -III or -IV breast cancer. All patients were treated with two to six cycles of fluorouracil-epirubicin and/or cyclophosphamid/epi-docetaxel. The Her2 protein and gene were assessed both on core needle biopsies prior to and on surgical specimens after completing chemotherapy using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) methods. Estrogen and progesterone receptors (ER/PR) were also determined on both samples using IHC. Her2 status was modified in eight patients using IHC (35%) and in three patients using FISH (13%). Changes in ER/PR expression were detected in seven patients (30%). Our data suggest that alterations of the Her2 gene can occur, although not usually after primary or neoadjuvant chemotherapy. However, changes in ER/PR status seem to be a more common event; thus, both can lead to different therapeutic options. Intratumoral heterogeneity as well as sampling variations can contribute to modification of the Her2 status after primary chemotherapy.

  19. Outcomes of Ahmed glaucoma valve implantation in advanced primary congenital glaucoma with previous surgical failure

    PubMed Central

    Huang, Jingjing; Lin, Jialiu; Wu, Ziqiang; Xu, Hongzhi; Zuo, Chengguo; Ge, Jian

    2015-01-01

    Purpose The purpose of this study was to evaluate the intermediate surgical results of Ahmed glaucoma valve (AGV) implantation in patients less than 7 years of age, with advanced primary congenital glaucoma who have failed previous surgeries. Patients and methods Consecutive patients with advanced primary congenital glaucoma that failed previous operations and had undergone subsequent AGV implantation were evaluated retrospectively. Surgical success was defined as 1) intraocular pressure (IOP) ≥6 and ≤21 mmHg; 2) IOP reduction of at least 30% relative to preoperative values; and 3) without the need for additional surgical intervention for IOP control, loss of light perception, or serious complications. Results Fourteen eyes of eleven patients were studied. Preoperatively, the average axial length was 27.71±1.52 (25.56–30.80) mm, corneal diameter was 14.71±1.07 (13.0–16.0) mm, cup-to-disc ratio was 0.95±0.04 (0.9–1.0), and IOP was 39.5±5.7 (30–55) mmHg. The mean follow-up time was 18.29±10.96 (5–44, median 18) months. There were significant reductions in IOPs and the number of glaucoma medications (P<0.001) postoperatively. The IOPs after operation were 11.3±3.4, 13.6±5.1, 16.3±2.7, and 16.1±2.6 mmHg at 1 month, 6 months, 12 months, and 18 months, respectively. Kaplan–Meier estimates of the cumulative probability of valve success were 85.7%, 71.4%, and 71.4% at 6, 12, and 18 months, respectively. Severe surgical complications, including erosion of tube, endophthalmitis, retinal detachment, choroidal detachment, and delayed suprachoroidal hemorrhage, occurred in 28.6% cases. Conclusion AGV implantation remains a viable option for patients with advanced primary congenital glaucoma unresponsive to previous surgical intervention, despite a relatively high incidence of severe surgical complications. PMID:26082610

  20. [Towards universal access to health care: incorporation of advanced practice nurses in primary care].

    PubMed

    Aguirre-Boza, Francisca; Achondo, Bernardita

    2016-10-01

    To move towards universal access to health, the Pan American Health Organization recommends strengthening primary health care (PHC). One of the strategies is to increase the number qualified professionals, both medical and non-medical, working in PHC. In Chile there is a lack of professionals in this level of care, hampering the provision of health. Physicians still prefer secondary and tertiary levels of health. International experience has shown that advanced practice nurses (APN), specialists in PHC are cost-effective professionals able to deliver a complete and quality care to patients. Strong evidence demonstrates the benefits that APN could provide to the population, delivering nursing care that incorporates medical tasks, for example in patients with chronic diseases, allowing greater availability of medical hours for patients requiring more complex management. The success in the implementation of this new role requires the support of the health team, especially PHC physicians, endorsing and promoting the benefits of the APN for the population.

  1. Efficacy and safety of benzalkonium chloride-free fixed-dose combination of latanoprost and timolol in patients with open-angle glaucoma or ocular hypertension

    PubMed Central

    Bhagat, Purvi; Sodimalla, Kalyani; Paul, Chandrima; Pandav, Surinder S; Raman, Ganesh V; Ramakrishnan, Rengappa; Joshi, Abhijeet; Raut, Atul

    2014-01-01

    Background Benzalkonium chloride (BAK) is a common preservative in topical ocular preparations; however, prolonged use may lead to deleterious effects on the ocular surface, affecting quality of life and reducing adherence to treatment and overall outcomes. This study compared the intraocular pressure (IOP)-lowering efficacy and safety of a novel once-daily, BAK-free, fixed-dose combination of latanoprost plus timolol with latanoprost or timolol administered as monotherapy or concomitantly. Methods This was a 6-week, randomized, open-label, parallel-group, active-controlled study in patients aged ≥18 years with open-angle glaucoma or ocular hypertension. A total of 227 patients were randomized to either a once-daily, BAK-free, fixed-dose combination of latanoprost 0.005%/timolol 0.5% ophthalmic solution or concomitant administration of once-daily latanoprost 0.005% plus twice-daily timolol 0.5% or once-daily latanoprost 0.005% monotherapy, or twice-daily timolol 0.5% monotherapy. Efficacy end points were assessed at three time points on visits at weeks 1, 2, 4, and 6 versus baseline. Results The IOP-lowering efficacy of the fixed-dose combination of latanoprost/timolol was similar to that of latanoprost plus timolol administered concomitantly at all time points (mean IOP difference and 95% confidence interval within ±1.5 mmHg; P=0.4223 to P=0.9981). The fixed-dose combination of latanoprost/timolol demonstrated significantly better IOP-lowering efficacy than timolol monotherapy at all time points (P=0.001 to P<0.0001) and significantly better IOP-lowering efficacy than latanoprost monotherapy at all time points. Responder rates on at least one time point and on at least two time points with fixed-dose combination latanoprost/timolol were similar to those with concomitant latanoprost plus timolol (85.5% versus 82.1%, P=0.6360; 78.2% versus 75%, P=0.6923), but significantly better than either latanoprost or timolol monotherapy (68.5%, P=0.0355; 55.4%, P=0.0005; 57

  2. A Major QTL, Which Is Co-located with cly1, and Two Minor QTLs Are Associated with Glume Opening Angle in Barley (Hordeum vulgare L.)

    PubMed Central

    Zhang, XinZhong; Guo, BaoJian; Lan, GuoFang; Li, HongTao; Lin, Shen; Ma, Jun; Lv, Chao; Xu, RuGen

    2016-01-01

    Cleistogamous and chasmogamous are two opposing phenomena for flowering in barley. Cleistogamy limits the rate of outcrossing, and increases the cost of producing hybrid barley seeds. Selecting chasmogamous lines with a large glume opening angle (GOA) is essential for the utilization of barley heterosis. In the current study, 247 DH lines derived from a cross between Yangnongpi7 and Yang0187 were used to identify and validate quantitative trait loci (QTLs) associated with the GOA in different environments using SSR markers. Three QTLs associated with barley GOA were mapped on chromosomes 2H and 7H. The major QTL QGOA-2H-2 was mapped on chromosome 2H with the flanking markers of KDH and GBM1498, explaining 63.92% of the phenotypic variation. The marker KDH was developed from the gene Cly1, which was the candidate gene for QGOA-2H-2. This new marker can be used to identify barley chasmogamous lines with a large GOA. The two minor QTLs were validated at all three locations across two seasons after removing DH lines carrying the candidate gene Cly1 of QGOA-2H-2. PMID:27822223

  3. Cisplatin and Flavopiridol in Treating Patients With Advanced Ovarian Epithelial Cancer or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2014-05-06

    Recurrent Ovarian Epithelial Cancer; Recurrent Primary Peritoneal Cavity Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Primary Peritoneal Cavity Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Primary Peritoneal Cavity Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Primary Peritoneal Cavity Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Primary Peritoneal Cavity Cancer

  4. Kinetics and advanced digester design for anaerobic digestion of water hyacinth and primary sludge

    SciTech Connect

    Chynoweth, D.P.; Dolenc, D.A.; Ghosh, S.; Henry, M.P.; Jerger, D.E.; Srivastava, V.J.

    1982-01-01

    A research program centered around a facility located at Walt Disney World (WDW) is in progress to evaluate the use of water hyacinth (WH) for secondary and tertiary wastewater treatment, to optimize growth of WH under these conditions, and to convert the resultant primary sludge (PS) and WH to methane via anaerobic digestion. This article describes the status of the biogasification component of this program, which includes baseline and advanced digestion experiments with individual feeds and blends and the design of an experimental test unit (ETU) to be installed at WDW. Experiments with several blends demonstrated that methane yields can be predicted from the fractional content and methane yield of each component. The process was found to adhere to the Monod kinetic model for microbial growth, and associated kinetic parameters were developed for various feed combinations. A novel upflow digester is achieving significantly higher conversion than a stirred-tank digester. Of several pretreatment techniques used, only alkaline treatment resulted in increased biodegradability. A larger scale (4.5 m/sup 3/) experimental test unit is being designed for installation at WDW in 1982. 13 figures, 4 tables.

  5. Performic acid (PFA): tests on an advanced primary effluent show promising disinfection performance.

    PubMed

    Gehr, R; Chen, D; Moreau, M

    2009-01-01

    Performic acid, or PFA (CH(2)O(3)), is a well-known oxidizing agent and disinfectant in the medical field and food industry. It has recently become available on a commercial scale for potential use in wastewater disinfection. This study investigated its application to an advanced primary effluent which is recalcitrant to disinfection by UV and peracetic acid (PAA). Methods were developed for determining PFA concentrations in stock solutions as well as in residual concentrations in the wastewater. Batch and continuous-flow pilot studies showed a correlation between log fecal coliform removals and PFA doses. A PFA dose of approximately 3.4 mg/L and a contact time of 45 minutes could achieve 3-logs removal, and almost total disinfection could be achieved using a dose of 6 mg/L. The by-products of PFA addition are hydrogen peroxide and formic acid (CHOOH), neither of which is considered to be toxic to aquatic fauna at the doses required for disinfection.

  6. Three Toxic Heavy Metals in Open-Angle Glaucoma with Low-Teen and High-Teen Intraocular Pressure: A Cross-Sectional Study from South Korea

    PubMed Central

    Lee, Si Hyung; Kang, Eun Min; Kim, Gyu Ah; Kwak, Seung Woo; Kim, Joon Mo; Bae, Hyoung Won; Seong, Gong Je; Kim, Chan Yun

    2016-01-01

    Background To investigate the association between heavy metal levels and open-angle glaucoma (OAG) with low- and high-teen baseline intraocular pressure (IOP) using a population-based study design. Methods This cross-sectional study included 5,198 participants older than 19 years of age who participated in the Korean National Health and Nutrition Examination Survey (KNHANES) from 2008 to 2012 and had blood heavy metal levels available. The OAG with normal baseline IOP (IOP ≤ 21 mmHg) subjects were stratified into low-teen OAG (baseline IOP ≤ 15 mmHg) and high-teen OAG (15 mmHg < baseline IOP ≤ 21 mmHg), and the association between blood lead, mercury, and cadmium levels and glaucoma prevalence was assessed for low- and high-teen OAG. Results The adjusted geometric mean of blood cadmium levels was significantly higher in subjects with low-teen OAG than that of the non-glaucomatous group (P = 0.028), whereas there were no significant differences in blood lead and mercury levels. After adjusting for potential confounders, the low-teen OAG was positively associated with log-transformed blood cadmium levels (OR, 1.41; 95% confidence interval (CI), 1.03–1.93; P = 0.026). For high-teen OAG, log-transformed blood levels of the three heavy metals were not associated with disease prevalence. The association between log-transformed blood cadmium levels and low-teen OAG was significant only in men (OR, 1.65; 95% CI, 1.10–2.48; P = 0.016), and not in women (OR, 1.10; 95% CI, 0.66–1.85; P = 0.709). Conclusions The results of this study suggest that cadmium toxicity could play a role in glaucoma pathogenesis, particularly in men and in OAG with low-teen baseline IOP. PMID:27768724

  7. Advance Care Planning in Patients with Primary Malignant Brain Tumors: A Systematic Review

    PubMed Central

    Song, Krystal; Amatya, Bhasker; Voutier, Catherine; Khan, Fary

    2016-01-01

    Advance care planning (ACP) is a process of reflection and communication of a person’s future health care preferences, and has been shown to improve end-of-life (EOL) care for patients. The aim of this systematic review is to present an evidence-based overview of ACP in patients with primary malignant brain tumors (pmBT). A comprehensive literature search was conducted using medical and health science electronic databases (PubMed, Cochrane, Embase, MEDLINE, ProQuest, Social Care Online, Scopus, and Web of Science) up to July 2016. Manual search of bibliographies of articles and gray literature search were also conducted. Two independent reviewers selected studies, extracted data, and assessed the methodologic quality of the studies using the Critical Appraisal Skills Program’s appraisal tools. All studies were included irrespective of the study design. A meta-analysis was not possible due to heterogeneity amongst included studies; therefore, a narrative analysis was performed for best evidence synthesis. Overall, 19 studies were included [1 randomized controlled trial (RCT), 17 cohort studies, 1 qualitative study] with 4686 participants. All studies scored “low to moderate” on the methodological quality assessment, implying high risk of bias. A single RCT evaluating a video decision support tool in facilitating ACP in pmBT patients showed a beneficial effect in promoting comfort care and gaining confidence in decision-making. However, the effect of the intervention on quality of life and care at the EOL were unclear. There was a low rate of use of ACP discussions at the EOL. Advance directive completion rates and place of death varied between different studies. Positive effects of ACP included lower hospital readmission rates, and intensive care unit utilization. None of the studies assessed mortality outcomes associated with ACP. In conclusion, this review found some beneficial effects of ACP in pmBT. The literature still remains limited in this area, with

  8. Advance Care Planning in Patients with Primary Malignant Brain Tumors: A Systematic Review.

    PubMed

    Song, Krystal; Amatya, Bhasker; Voutier, Catherine; Khan, Fary

    2016-01-01

    Advance care planning (ACP) is a process of reflection and communication of a person's future health care preferences, and has been shown to improve end-of-life (EOL) care for patients. The aim of this systematic review is to present an evidence-based overview of ACP in patients with primary malignant brain tumors (pmBT). A comprehensive literature search was conducted using medical and health science electronic databases (PubMed, Cochrane, Embase, MEDLINE, ProQuest, Social Care Online, Scopus, and Web of Science) up to July 2016. Manual search of bibliographies of articles and gray literature search were also conducted. Two independent reviewers selected studies, extracted data, and assessed the methodologic quality of the studies using the Critical Appraisal Skills Program's appraisal tools. All studies were included irrespective of the study design. A meta-analysis was not possible due to heterogeneity amongst included studies; therefore, a narrative analysis was performed for best evidence synthesis. Overall, 19 studies were included [1 randomized controlled trial (RCT), 17 cohort studies, 1 qualitative study] with 4686 participants. All studies scored "low to moderate" on the methodological quality assessment, implying high risk of bias. A single RCT evaluating a video decision support tool in facilitating ACP in pmBT patients showed a beneficial effect in promoting comfort care and gaining confidence in decision-making. However, the effect of the intervention on quality of life and care at the EOL were unclear. There was a low rate of use of ACP discussions at the EOL. Advance directive completion rates and place of death varied between different studies. Positive effects of ACP included lower hospital readmission rates, and intensive care unit utilization. None of the studies assessed mortality outcomes associated with ACP. In conclusion, this review found some beneficial effects of ACP in pmBT. The literature still remains limited in this area, with lack of

  9. A Challenging Surgical Approach to Locally Advanced Primary Urethral Carcinoma: A Case Report and Literature Review.

    PubMed

    Lucarelli, Giuseppe; Spilotros, Marco; Vavallo, Antonio; Palazzo, Silvano; Miacola, Carlos; Forte, Saverio; Matera, Matteo; Campagna, Marcello; Colamonico, Ottavio; Schiralli, Francesco; Sebastiani, Francesco; Di Cosmo, Federica; Bettocchi, Carlo; Di Lorenzo, Giuseppe; Buonerba, Carlo; Vincenti, Leonardo; Ludovico, Giuseppe; Ditonno, Pasquale; Battaglia, Michele

    2016-05-01

    Primary urethral carcinoma (PUC) is a rare and aggressive cancer, often underdetected and consequently unsatisfactorily treated. We report a case of advanced PUC, surgically treated with combined approaches.A 47-year-old man underwent transurethral resection of a urethral lesion with histological evidence of a poorly differentiated squamous cancer of the bulbomembranous urethra. Computed tomography (CT) and bone scans excluded metastatic spread of the disease but showed involvement of both corpora cavernosa (cT3N0M0). A radical surgical approach was advised, but the patient refused this and opted for chemotherapy. After 17 months the patient was referred to our department due to the evidence of a fistula in the scrotal area. CT scan showed bilateral metastatic disease in the inguinal, external iliac, and obturator lymph nodes as well as the involvement of both corpora cavernosa. Additionally, a fistula originating from the right corpus cavernosum extended to the scrotal skin. At this stage, the patient accepted the surgical treatment, consisting of different phases. Phase I: Radical extraperitoneal cystoprostatectomy with iliac-obturator lymph nodes dissection. Phase II: Creation of a urinary diversion through a Bricker ileal conduit. Phase III: Repositioning of the patient in lithotomic position for an overturned Y skin incision, total penectomy, fistula excision, and "en bloc" removal of surgical specimens including the bladder, through the perineal breach. Phase IV: Right inguinal lymphadenectomy.The procedure lasted 9-and-a-half hours, was complication-free, and intraoperative blood loss was 600 mL. The patient was discharged 8 days after surgery. Pathological examination documented a T4N2M0 tumor. The clinical situation was stable during the first 3 months postoperatively but then metastatic spread occurred, not responsive to adjuvant chemotherapy, which led to the patient's death 6 months after surgery.Patients with advanced stage tumors of the

  10. Radiotherapy and Hyperthermia for Treatment of Primary Locally Advanced Cervix Cancer: Results in 378 Patients

    SciTech Connect

    Franckena, Martine Lutgens, Ludy C.; Koper, Peter C.; Kleynen, Catharina E.; Steen-Banasik, Elsbieta M. van der; Jobsen, Jan J.; Leer, Jan Willem; Creutzberg, Carien L.; Dielwart, Michel F.; Norden, Yvette van; Canters, Richard A.M.; Rhoon, Gerard C. van; Zee, Jacoba van der

    2009-01-01

    Purpose: To report response rate, pelvic tumor control, survival, and late toxicity after treatment with combined radiotherapy and hyperthermia (RHT) for patients with locally advanced cervical carcinoma (LACC) and compare the results with other published series. Methods and Materials: From 1996 to 2005, a total of 378 patients with LACC (International Federation of Gynecology and Obstetrics Stage IB2-IVA) were treated with RHT. External beam radiotherapy (RT) was applied to 46-50.4 Gy and combined with brachytherapy. The hyperthermia (HT) was prescribed once weekly. Primary end points were complete response (CR) and local control. Secondary end points were overall survival, disease-specific survival, and late toxicity. Patient, tumor, and treatment characteristics predictive for the end points were identified in univariate and multivariate analyses. Results: Overall, a CR was achieved in 77% of patients. At 5 years, local control, disease-specific survival, and incidence of late toxicity Common Terminology Criteria for Adverse Events Grade 3 or higher were 53%, 47%, and 12%, respectively. In multivariate analysis, number of HT treatments emerged as a predictor of outcome in addition to commonly identified prognostic factors. Conclusions: The CR, local control, and survival rates are similar to previously observed results of RHT in the randomized Dutch Deep Hyperthermia Trial. Reported treatment results for currently applied combined treatment modalities (i.e., RT with chemotherapy and/or HT) do not permit definite conclusions about which combination is superior. The present results confirm previously shown beneficial effects from adding HT to RT and justify the application of RHT as first-line treatment in patients with LACC as an alternative to chemoradiation.

  11. Efficacy of two trabecular micro-bypass stents combined with topical travoprost in open-angle glaucoma not controlled on two preoperative medications: 3-year follow-up

    PubMed Central

    Chang, David F; Donnenfeld, Eric D; Katz, L Jay; Voskanyan, Lilit; Ahmed, Iqbal Ike K; Samuelson, Thomas W; Giamporcaro, Jane Ellen; Hornbeak, Dana M; Solomon, Kerry D

    2017-01-01

    Purpose To evaluate the long-term intraocular pressure (IOP)-lowering effect and safety parameters following treatment with two trabecular micro-bypass stents and topical prostaglandin in phakic eyes with open-angle glaucoma (OAG) not controlled on two preoperative medications. Methods This prospective, single-arm, unmasked study enrolled 39 qualified phakic eyes with OAG not controlled on 2 medications, preoperative medicated IOP of 18–30 mmHg, and IOP following medication washout of 22–38 mmHg. Two trabecular micro-bypass stents were implanted as a standalone procedure, and travoprost was started on postoperative day 1. Evaluations included IOP, best-corrected visual acuity, medication use, fundus and slit-lamp examinations, visual field, cup:disc ratio, central corneal thickness, and ocular complications. Data through 18 months were summarized previously. Thirty-seven of the original 39 subjects have been followed for 3 years postoperatively; follow-up is continuing for 5 years. Results At 3 years postoperative, 97% of eyes had achieved an IOP reduction of ≥20% from baseline with a reduction of 1 medication. Eighty-six percent of eyes had IOP of ≤18 mmHg with a reduction of 1 medication. Mean medicated IOP decreased to 14.0±2.6 mmHg on 1 medication versus 22.4±2.3 mmHg on 2 medications preoperatively. The mean unmedicated IOP decreased to 17.7±1.7 mmHg at 37 months from 25.3±1.9 mmHg preoperatively. Long-term postoperative adverse events included cataract surgery in 3 eyes due to cataract progression, and trabeculectomy in 1 eye due to uncontrolled IOP of 23 mmHg. No intraoperative or device-related adverse events occurred. Conclusion Significant and sustained reduction in IOP and medications with a favorable safety profile was shown through 3 years after implantation of 2 trabecular micro-bypass stents combined with postoperative travoprost in phakic OAG eyes uncontrolled on 2 preoperative medications. These findings demonstrate the long

  12. Association of Myopic Optic Disc Deformation with Visual Field Defects in Paired Eyes with Open-Angle Glaucoma: A Cross-Sectional Study

    PubMed Central

    Sawada, Yu; Hangai, Masanori; Ishikawa, Makoto; Yoshitomi, Takeshi

    2016-01-01

    Purpose To examine the association of myopia with the visual field (VF) defects in open-angle glaucoma (OAG) using paired eyes to eliminate the effect of unknown confounding factors that are diverse among individuals. Methods One hundred eighteen eyes of 59 subjects with myopia (spherical equivalent [SE] ≥ -2 diopter [D] and axial length ≥ 24.0 mm) whose intra-ocular pressure between paired eyes was similar and the mean deviation (MD) of the Humphrey VF test differed by more than 6 dB were included. Refractive errors (SE, axial length) and parameters associated with the papillary and parapapillary myopic deformation (tilt ratio, torsion angle, and β-zone parapapillary atrophy [PPA] area without Bruch’s membrane) were measured in each eye. The paired eyes were divided into worse and better eyes according to the MD of the VF, and parameters were compared between them. Further, multiple linear regression analysis was performed to examine the correlation of the difference in various parameters with the MD difference between paired eyes. Results The SE of all eyes was -6.39 ± 2.15 D (mean ± standard deviation) and axial length was 26.42 ± 1.07 mm. MD of the worse and better VF eyes were -13.56 ± 6.65 dB and -4.87 ± 5.32 dB, respectively. Eyes with worse VFs had significantly greater SE, axial length, tilt ratio, and PPA area without Bruch’s membrane than those with better VFs (all P < 0.05). In multiple linear regression analysis, the difference of the MD between paired eyes was significantly correlated with the difference in the tilt ratio and PPA area without Bruch’s membrane. Conclusion The myopic papillary and parapapillary deformations, but not refractive error itself, were related to the worse VF in paired eyes with OAG. This suggests that myopia influences the severity of the glaucomatous VF defects via structural deformation. PMID:27571303

  13. Molecular Evolution Patterns in Metastatic Lymph Nodes Reflect the Differential Treatment Response of Advanced Primary Lung Cancer.

    PubMed

    Um, Sang-Won; Joung, Je-Gun; Lee, Hyun; Kim, Hojoong; Kim, Kyu-Tae; Park, Jinha; Hayes, D Neil; Park, Woong-Yang

    2016-11-15

    Tumor heterogeneity influences the clinical outcome of patients with cancer, and the diagnostic method to measure the tumor heterogeneity needs to be developed. We analyzed genomic features on pairs of primary and multiple metastatic lymph nodes from six patients with lung cancer using whole-exome sequencing and RNA sequencing. Although somatic single-nucleotide variants were shared in primary lung cancer and metastases, tumor evolution predicted by the pattern of genomic alterations was matched to anatomic location of the tumors. Four of six cases exhibited a branched clonal evolution pattern. Lymph nodes with acquired somatic variants demonstrated resistance to the cancer treatment. In this study, we demonstrated that multiple biopsies and sequencing strategies for different tumor regions are required for a comprehensive understanding of the landscape of genetic alteration and for guiding targeted therapy in advanced primary lung cancer. Cancer Res; 76(22); 6568-76. ©2016 AACR.

  14. Non-invasive screening for NAFLD and advanced fibrosis in diabetes in primary care setting by MRI and MRE

    PubMed Central

    Doycheva, Iliana; Cui, Jeffrey; Nguyen, Phirum; Costa, Eduardo A.; Hooker, Jonathan; Hofflich, Heather; Bettencourt, Ricki; Brouha, Sharon; Sirlin, Claude B.; Loomba, Rohit

    2015-01-01

    SUMMARY Background Current guidelines do not recommend screening for nonalcoholic fatty liver disease (NAFLD) or advanced fibrosis. Patients with type 2 diabetes mellitus (T2DM) are known to be at increased risk for NAFLD and advanced fibrosis. Aim We aimed to assess the feasibility in diabetics in a primary care setting of screening for NAFLD and advanced fibrosis by using non-invasive magnetic resonance imaging (MRI) to estimate the hepatic proton density fat fraction (MRI-PDFF) and magnetic resonance elastography (MRE) to estimate hepatic stiffness. Methods We performed a cross-sectional analysis of a prospective study that included 100 (53% men) consecutively enrolled diabetics who did not have any other etiology of liver disease. All patients underwent a standardized research visit, laboratory tests, MRI-PDFF, and MRE. Results Mean (± SD) age and BMI was 59.7 (±11.2) years and 30.8 (±6.5) kg/m2, respectively. The prevalence of NAFLD (defined as MRI-PDFF ≥ 5%) and advanced fibrosis (defined as MRE ≥ 3.6 kPa) was 65% and 7.1%, respectively. One patient with advanced fibrosis had definite hepatocellular carcinoma. When compared to those without NAFLD, patients with NAFLD were younger (p=0.028) and had higher mean BMI (p=0.0008), waist circumference (p<0.0001) and prevalence of metabolic syndrome (84.6% vs. 40.0%, p<0.0001). Only 26% of those with NAFLD had elevated ALT. Conclusions This proof-of-concept study demonstrates that T2DM has significant rates of both NAFLD and advanced fibrosis. Concomitant screening for NAFLD and advanced fibrosis by using MRI-PDFF and MRE in T2DM is feasible and may be considered after validation in a larger cohort. PMID:26369383

  15. Rapid development of advanced liver fibrosis after acquisition of hepatitis C infection during primary HIV infection.

    PubMed

    Osinusi, Anu; Kleiner, David; Wood, Brad; Polis, Michael; Masur, Henry; Kottilil, Shyam

    2009-06-01

    We report the first reported case of a 61-year-old MSM who was diagnosed with syphilis, primary HIV infection, and acute hepatitis C (HCV) within the same time period who rapidly developed significant liver fibrosis within 6 months of acquisition of both infections. It has been well described that individuals with primary HIV infection have an increase in activated CD8+ T cells, which causes a state of immune activation as was evident in this patient. Acquisition of HCV during this time could have further skewed this response resulting in massive hepatocyte destruction, inflammation, and subsequent liver fibrosis. Recent literature suggest that MSM with primary HIV infection have higher rates of acquisition of HCV than other HIV-positive cohorts and HCV acquisition can occur very soon after acquiring HIV. This case of rapid hepatic fibrosis progression coupled with the increasing incidence of HCV in individuals with primary HIV infection demonstrates a need for this phenomenon to be studied more extensively.

  16. Changes in primary metabolites and polyphenols in the peel of "Braeburn" apples (Malus domestica Borkh.) during advanced maturation.

    PubMed

    Bizjak, Jan; Mikulic-Petkovsek, Maja; Stampar, Franci; Veberic, Robert

    2013-10-30

    During the two growing seasons the evolution of primary metabolites and wide range of polyphenols in the "Braeburn" apple peel during advanced maturation were investigated. During the five weeks sucrose significantly increased, whereas fructose and glucose fluctuated around the same level in one season and decreased in another. Regarding malic and citric acids, an expected decrease was recorded. The concentrations of hydroxycinnamic acids, dihydrochalcones, and flavanols remained quite constant or slightly decreased during advanced apple ripening. On the contrary an intensive accumulation of quercetin glycosides and anthocyanins took place during this period, starting with the onset of rapid formation approximately 3 weeks before the technological maturity of apples. Total phenolic content was relatively constant or slightly increased. The present results suggest that measures designed to improve the apple color and quality of "Braeburn" apples should be performed approximately 3-4 weeks before the expected technological maturity of apples.

  17. Successful Treatment of Advanced Primary Cutaneous Apocrine Carcinoma on the Scrotum with Systemic Chemotherapy and Radiotherapy Followed by Denosumab

    PubMed Central

    Furudate, Sadanori; Fujimura, Taku; Tsukada, Akira; Sato, Yota; Hidaka, Takanori; Tanita, Kayo; Kambayashi, Yumi; Haga, Takahiro; Hashimoto, Akira; Aiba, Setsuya

    2017-01-01

    Primary cutaneous apocrine carcinoma (PCAC) is a rare and highly aggressive cutaneous adnexal type of tumor that has a high metastasis rate and a poor prognosis. Although there are several case reports describing the successful treatment of PCAC with chemoradiotherapy or molecular targeting therapy, no standard therapy for the treatment of advanced PCAC has been established yet. Since receptor activator of nuclear factor kappa-B ligand (RANKL) is expressed in cancers of apocrine origin, leading to immunosuppression at the tumor site, we hypothesized that targeting RANKL with denosumab might be useful for the treatment of PCAC. In this report, we describe a case with advanced PCAC on the scrotum successfully treated with systemic chemotherapy using carboplatin and paclitaxel, and radiotherapy followed by denosumab. PMID:28203164

  18. Meeting EFA: Bangladesh Rural Advancement Committee (BRAC) Primary Schools. Case Study

    ERIC Educational Resources Information Center

    Chaboux, Collette

    2006-01-01

    This case study describes the Bangladesh Rural Advancement Committee (BRAC), which was formed to explore ways to help children from its rural development program gain access to improved education. Working mainly in rural areas, BRAC focused on improved quality through improved education service delivery, management detail, and finance. While…

  19. Development of a Thin Film Primary Surface Heat Exchanger for Advanced Power Cycles

    SciTech Connect

    Allison, Tim; Beck, Griffin; Bennett, Jeffrey; Hoopes, Kevin; Miller, Larry

    2016-06-29

    This project objective is to develop a high-temperature design upgrade for an existing primary surface heat exchanger so that the redesigned hardware is capable of operation in CO2 at temperatures up to 1,510°F (821°C) and pressure differentials up to 130 psi (9 bar). The heat exchanger is proposed for use as a recuperator in an advanced low-pressure oxy-fuel Brayton cycle that is predicted to achieve over 50% thermodynamic efficiency, although the heat exchanger could also be used in other high-temperature, low-differential pressure cycles. This report describes the progress to date, which includes continuing work performed to select and test new candidate materials for the recuperator redesign, final mechanical and thermal performance analysis results of various redesign concepts, and the preliminary design of a test loop for the redesigned recuperator including a budgetary estimate for detailed test loop design, procurement, and test operation. A materials search was performed in order to investigate high-temperature properties of many candidate materials, including high-temperature strength and nickel content. These properties were used to rank the candidate materials, resulting in a reduced list of nine materials for corrosion testing. Multiple test rigs were considered and analyzed for short-term corrosion testing and Thermal Gravimetric Analysis (TGA) was selected as the most cost-effective option for evaluating corrosion resistance of the candidate materials. In addition, tantalum, niobium, and chromium coatings were identified as potential options for increased corrosion resistance. The test results show that many materials exhibit relatively low weight gain rates, and that niobium and tantalum coatings may improve corrosion resistance for many materials, while chromium coatings appear to oxidize and debond quickly. Metallurgical analysis of alloys was also performed, showing evidence of intergranular attack in 282 that may cause long

  20. Advancing educational continuity in primary care residencies: an opportunity for patient-centered medical homes.

    PubMed

    Bowen, Judith L; Hirsh, David; Aagaard, Eva; Kaminetzky, Catherine P; Smith, Marie; Hardman, Joseph; Chheda, Shobhina G

    2015-05-01

    Continuity of care is a core value of patients and primary care physicians, yet in graduate medical education (GME), creating effective clinical teaching environments that emphasize continuity poses challenges. In this Perspective, the authors review three dimensions of continuity for patient care-informational, longitudinal, and interpersonal-and propose analogous dimensions describing continuity for learning that address both residents learning from patient care and supervisors and interprofessional team members supporting residents' competency development. The authors review primary care GME reform efforts through the lens of continuity, including the growing body of evidence that highlights the importance of longitudinal continuity between learners and supervisors for making competency judgments. The authors consider the challenges that primary care residency programs face in the wake of practice transformation to patient-centered medical home models and make recommendations to maximize the opportunity that these practice models provide. First, educators, researchers, and policy makers must be more precise with terms describing various dimensions of continuity. Second, research should prioritize developing assessments that enable the study of the impact of interpersonal continuity on clinical outcomes for patients and learning outcomes for residents. Third, residency programs should establish program structures that provide informational and longitudinal continuity to enable the development of interpersonal continuity for care and learning. Fourth, these educational models and continuity assessments should extend to the level of the interprofessional team. Fifth, policy leaders should develop a meaningful recognition process that rewards academic practices for training the primary care workforce.

  1. Use of activated sludge biomass as an agent for advanced primary separation.

    PubMed

    Araneda, Michael; Pavez, Javier; Luza, Benjamín; Jeison, David

    2017-05-01

    Conventional primary settling is a physical process of solid-liquid separation, normally presenting low removal efficiencies. Improvement of this separation process would result in energetic advantages: lower aeration requirements and higher biogas production form primary and secondary sludges. Secondary sludge has been proposed as a potential agent promoting an increase in primary separation efficiency. Few processes have been proposed, based on the cultivation of sludge under special conditions. However, one can speculate that regular sludge may have a similar effect. The aim of this research was to study that possibility. Sludges from different activated sludge reactors were tested. Results showed that COD removals were up to 55%, 2 times higher than that for simple settling. Under that condition, COD balances showed that aeration requirements would reduce 40%, and biogas production from primary and secondary sludges would increase 50%. It is inferred then that the application of activated sludge as an external agent represents an interesting alternative that have the potential to significantly improve energetic efficiency of sewage treatment plants.

  2. Glaukos iStent inject® Trabecular Micro-Bypass Implantation Associated with Cataract Surgery in Patients with Coexisting Cataract and Open-Angle Glaucoma or Ocular Hypertension: A Long-Term Study

    PubMed Central

    Martinez-de-la-Casa, Jose Maria; Diaz-Valle, David; Morales-Fernandez, Laura; Fernandez-Perez, Cristina; Garcia-Feijoo, Julian

    2016-01-01

    Purpose. To evaluate the long-term efficacy and safety of the iStent inject device (Glaukos Corporation, Laguna Hills, CA) combined with phacoemulsification in patients with coexistent cataract and open-angle glaucoma or ocular hypertension (OHT). Methods. A prospective, uncontrolled, nonrandomized, interventional case series study was conducted in patients with both mild or moderate open-angle glaucoma or OHT and cataract. Patients underwent cataract surgery along with the implant of two iStent inject devices. Outcome measures were intraocular pressure (IOP), topical hypotensive medications required, and best-corrected visual acuity (BCVA). Results. 20 patients were enrolled. Mean follow-up was 47.4 ± 18.46 months. Mean baseline IOP was 19.95 ± 3.71 mmHg with medication and 26 ± 3.11 mmHg after washout. Mean end-follow-up IOP was 16.25 ± 1.99 mmHg, representing an IOP decrease of 36.92%, 9.74 ± 3.14 mmHg (P < 0.001), from baseline washout IOP. The mean number of medications was significantly reduced from 1.3 ± 0.66 to 0.75 ± 0.79 (P = 0.017). 45% of patients were medication-free by the end of follow-up. Mean log⁡MAR BCVA improved significantly from 0.42 ± 0.16 to 0.18 ± 0.16 (P < 0.001). No complications of surgery were observed. Conclusion. The iStent inject device combined with cataract surgery served to significantly reduce both IOP and medication use in the long term in patients with coexistent open-angle glaucoma or ocular hypertension (OHT) and cataract. PMID:27882243

  3. Building strong relationships between conservation genetics and primary industry leads to mutually beneficial genomic advances.

    PubMed

    Galla, Stephanie J; Buckley, Thomas R; Elshire, Rob; Hale, Marie L; Knapp, Michael; McCallum, John; Moraga, Roger; Santure, Anna W; Wilcox, Phillip; Steeves, Tammy E

    2016-11-01

    Several reviews in the past decade have heralded the benefits of embracing high-throughput sequencing technologies to inform conservation policy and the management of threatened species, but few have offered practical advice on how to expedite the transition from conservation genetics to conservation genomics. Here, we argue that an effective and efficient way to navigate this transition is to capitalize on emerging synergies between conservation genetics and primary industry (e.g., agriculture, fisheries, forestry and horticulture). Here, we demonstrate how building strong relationships between conservation geneticists and primary industry scientists is leading to mutually-beneficial outcomes for both disciplines. Based on our collective experience as collaborative New Zealand-based scientists, we also provide insight for forging these cross-sector relationships.

  4. Association between vascular-poor area of primary tumors and epidermal growth factor receptor gene status in advanced lung adenocarcinoma.

    PubMed

    Togashi, Yosuke; Masago, Katsuhiro; Kubo, Takeshi; Fujimoto, Daichi; Sakamori, Yuichi; Nagai, Hiroki; Kim, Young Hak; Togashi, Kaori; Mishima, Michiaki

    2012-12-01

    Mutation of the epidermal growth factor receptor gene (EGFR mutation) is a very important marker in the treatment for non-small cell lung cancer. Since signaling from this receptor induces tumor-associated angiogenesis, we hypothesized that lung cancers with EGFR mutations tend to develop locally with increased angiogenesis. Thus, the association between vascular-poor area of primary tumors and EGFR status was retrospectively investigated in advanced lung adenocarcinomas. To assess vascular-poor area, contrast-enhanced computed tomography scans taken before initial treatment for lung cancer were analyzed, together with primary tumor location (peripheral or central) and size. We analyzed 178 patients with advanced lung adenocarcinoma. EGFR mutations were detected in 95 of the 178 patients (53.4 %). EGFR mutation was found to be significantly related to women (P = 0.0070), never-smokers (P < 0.0001), and tumors without vascular-poor area (P < 0.0001). Based on a multivariate analysis, presence of EGFR mutations was independently associated with never-smokers (P = 0.0046), lack of vascular-poor area (P = 0.0001), and tumor size >30 mm (P = 0.0080). EGFR mutations were found in 41 of 51 never-smokers without vascular-poor area (80.4 %), 19 of 36 never-smokers with vascular-poor area (52.8 %), 19 of 37 current or former-smokers without vascular-poor area (51.4 %), and 16 of 54 current or former-smokers with vascular-poor area (29.6 %). This study showed an association between vascular-poor area of primary tumors and EGFR status. As a consequence, evaluation using a combination of smoking status and vascular-poor area allows us to predict presence of EGFR mutations at a high frequency.

  5. A station blackout simulation for the Advanced Neutron Source Reactor using the integrated primary and secondary system model

    SciTech Connect

    Schneider, E.A.

    1994-06-01

    The Advanced Neutron Source Reactor (ANSR) is a research reactor to be built at Oak Ridge National Laboratory. This paper deals with thermal-hydraulic analysis of ANSR`s cooling systems during nominal and transient conditions, with the major effort focusing upon the construction and testing of computer models of the reactor`s primary, secondary and reflector vessel cooling systems. The code RELAP5 was used to simulate transients, such as loss of coolant accidents and loss of off-site power, as well as to model the behavior of the reactor in steady state. Three stages are involved in constructing and using a RELAP5 model: (1) construction and encoding of the desired model, (2) testing and adjustment of the model until a satisfactory steady state is achieved, and (3) running actual transients using the steady-state results obtained earlier as initial conditions. By use of the ANSR design specifications, a model of the reactor`s primary and secondary cooling systems has been constructed to run a transient simulating a loss of off-site power. This incident assumes a pump coastdown in both the primary and secondary loops. The results determine whether the reactor can survive the transition from forced convection to natural circulation.

  6. Advances in understanding the pathogenesis of primary familial and congenital polycythaemia.

    PubMed

    Huang, Lily J; Shen, Yu-Min; Bulut, Gamze B

    2010-03-01

    Primary familial and congenital polycythemia (PFCP) is an autosomal-dominant proliferative disorder characterized by erythrocytosis and hypersensitivity of erythroid progenitors to erythropoietin (Epo). Several lines of evidence suggest a causal role of truncated erythropoietin receptor (EpoR) in this disease. In this review, we discuss PFCP in the context of erythrocytosis and EpoR signalling. We focus on recent studies describing mechanisms underlying Epo-dependent EpoR down-regulation. One mechanism depends on internalization mediated through the p85 regulatory subunit of the Phosphoinositide 3-Kinase, and the other utilizes ubiquitin-based proteasomal degradation. Truncated PFCP EpoRs are not properly down-regulated upon stimulation, underscoring the importance of these mechanisms in the pathogenesis of PFCP.

  7. Safety Design Strategy for the Advanced Test Reactor Primary Coolant Pump and Motor Replacement Project

    SciTech Connect

    Noel Duckwitz

    2011-06-01

    In accordance with the requirements of U.S. Department of Energy (DOE) Order 413.3B, “Program and Project Management for the Acquisition of Capital Assets,” safety must be integrated into the design process for new or major modifications to DOE Hazard Category 1, 2, and 3 nuclear facilities. The intended purpose of this requirement involves the handling of hazardous materials, both radiological and chemical, in a way that provides adequate protection to the public, workers, and the environment. Requirements provided in DOE Order 413.3B and DOE Order 420.1B, “Facility Safety,” and the expectations of DOE-STD-1189-2008, “Integration of Safety into the Design Process,” provide for identification of hazards early in the project and use of an integrated team approach to design safety into the facility. This safety design strategy provides the basic safety-in-design principles and concepts that will be used for the Advanced Test Reactor Reliability Sustainment Project. While this project does not introduce new hazards to the ATR, it has the potential for significant impacts to safety-related systems, structures, and components that are credited in the ATR safety basis and are being replaced. Thus the project has been determined to meet the definition of a major modification and is being managed accordingly.

  8. Primary debulking surgery for advanced ovarian cancer: are you a believer or a dissenter?

    PubMed

    Schorge, John O; Clark, Rachel M; Lee, Susanna I; Penson, Richard T

    2014-12-01

    Nothing stirs the collective soul of primary debulking surgery (PDS) advocates like hard data suggesting equivalent outcomes of neoadjuvant chemotherapy (NAC). These opposing views have even metaphorically come to blows at the highly entertaining "SGO Fight Night" that took place during the 2008 Annual Meeting on Women's Cancer, replete with teams supporting each of the would-be gladiators. Decades of retrospective data supporting the clinical benefit of PDS has recently been challenged by the publication in 2010 of a randomized phase III trial conducted in Europe supporting the clinical efficacy of NAC. Naturally, a firestorm of criticism among believers ensued, yet practice patterns within the United States did slowly change, suggesting an emerging block of dissenters. Another randomized phase III European trial, as presented in abstract form in 2013, showed similar findings. Few other topics within the field of gynecologic oncology have participants so entrenched in the "corners" of their existing practice patterns. This review attempts to consolidate the current evidence supporting both sides so that the patient can be declared the winner.

  9. Advanced composites structural concepts and materials technologies for primary aircraft structures: Structural response and failure analysis

    NASA Technical Reports Server (NTRS)

    Dorris, William J.; Hairr, John W.; Huang, Jui-Tien; Ingram, J. Edward; Shah, Bharat M.

    1992-01-01

    Non-linear analysis methods were adapted and incorporated in a finite element based DIAL code. These methods are necessary to evaluate the global response of a stiffened structure under combined in-plane and out-of-plane loading. These methods include the Arc Length method and target point analysis procedure. A new interface material model was implemented that can model elastic-plastic behavior of the bond adhesive. Direct application of this method is in skin/stiffener interface failure assessment. Addition of the AML (angle minus longitudinal or load) failure procedure and Hasin's failure criteria provides added capability in the failure predictions. Interactive Stiffened Panel Analysis modules were developed as interactive pre-and post-processors. Each module provides the means of performing self-initiated finite elements based analysis of primary structures such as a flat or curved stiffened panel; a corrugated flat sandwich panel; and a curved geodesic fuselage panel. This module brings finite element analysis into the design of composite structures without the requirement for the user to know much about the techniques and procedures needed to actually perform a finite element analysis from scratch. An interactive finite element code was developed to predict bolted joint strength considering material and geometrical non-linearity. The developed method conducts an ultimate strength failure analysis using a set of material degradation models.

  10. Advances in the quantification of mitochondrial function in primary human immune cells through extracellular flux analysis

    PubMed Central

    Ip, Blanche C.; Habib, Chloe; Ritou, Eleni; Grammatopoulos, Tom N.; Steenkamp, Devin; Dooms, Hans; Apovian, Caroline M.; Lauffenburger, Douglas A.

    2017-01-01

    Numerous studies show that mitochondrial energy generation determines the effectiveness of immune responses. Furthermore, changes in mitochondrial function may regulate lymphocyte function in inflammatory diseases like type 2 diabetes. Analysis of lymphocyte mitochondrial function has been facilitated by introduction of 96-well format extracellular flux (XF96) analyzers, but the technology remains imperfect for analysis of human lymphocytes. Limitations in XF technology include the lack of practical protocols for analysis of archived human cells, and inadequate data analysis tools that require manual quality checks. Current analysis tools for XF outcomes are also unable to automatically assess data quality and delete untenable data from the relatively high number of biological replicates needed to power complex human cell studies. The objectives of work presented herein are to test the impact of common cellular manipulations on XF outcomes, and to develop and validate a new automated tool that objectively analyzes a virtually unlimited number of samples to quantitate mitochondrial function in immune cells. We present significant improvements on previous XF analyses of primary human cells that will be absolutely essential to test the prediction that changes in immune cell mitochondrial function and fuel sources support immune dysfunction in chronic inflammatory diseases like type 2 diabetes. PMID:28178278

  11. Advances in the quantification of mitochondrial function in primary human immune cells through extracellular flux analysis.

    PubMed

    Nicholas, Dequina; Proctor, Elizabeth A; Raval, Forum M; Ip, Blanche C; Habib, Chloe; Ritou, Eleni; Grammatopoulos, Tom N; Steenkamp, Devin; Dooms, Hans; Apovian, Caroline M; Lauffenburger, Douglas A; Nikolajczyk, Barbara S

    2017-01-01

    Numerous studies show that mitochondrial energy generation determines the effectiveness of immune responses. Furthermore, changes in mitochondrial function may regulate lymphocyte function in inflammatory diseases like type 2 diabetes. Analysis of lymphocyte mitochondrial function has been facilitated by introduction of 96-well format extracellular flux (XF96) analyzers, but the technology remains imperfect for analysis of human lymphocytes. Limitations in XF technology include the lack of practical protocols for analysis of archived human cells, and inadequate data analysis tools that require manual quality checks. Current analysis tools for XF outcomes are also unable to automatically assess data quality and delete untenable data from the relatively high number of biological replicates needed to power complex human cell studies. The objectives of work presented herein are to test the impact of common cellular manipulations on XF outcomes, and to develop and validate a new automated tool that objectively analyzes a virtually unlimited number of samples to quantitate mitochondrial function in immune cells. We present significant improvements on previous XF analyses of primary human cells that will be absolutely essential to test the prediction that changes in immune cell mitochondrial function and fuel sources support immune dysfunction in chronic inflammatory diseases like type 2 diabetes.

  12. New insights into molecular diagnostic pathology of primary liver cancer: Advances and challenges.

    PubMed

    Cong, Wen-Ming; Wu, Meng-Chao

    2015-11-01

    Primary liver cancer (PLC) is one of the most common malignancies worldwide with increasing incidence and accounts for the third leading cause of cancer-related mortality. Traditional morphopathology primarily emphasizes qualitative diagnosis of PLC, which is not sufficient to resolve the major concern of increasing the long-term treatment efficacy of PLC in clinical management for the modern era. Since the beginning of the 21st century, molecular pathology has played an active role in the investigation of the evaluation of the metastatic potential of PLC, detection of drug targets, prediction of recurrence risks, analysis of clonal origins, evaluation of the malignancy trend of precancerous lesions, and determination of clinical prognosis. As a result, many new progresses have been obtained, and new strategies of molecular-pathological diagnosis have been formed. Moreover, the new types of pathobiological diagnosis indicator systems for PLC have been preliminarily established. These achievements provide valuable molecular pathology-based guide for clinical formulation of individualized therapy programs for PLC. This review article briefly summarizes some relevant progresses of molecular-pathological diagnosis of PLC from the perspective of clinical translational application other than basic experimental studies.

  13. Primary Tumor Site as a Predictor of Treatment Outcome for Definitive Radiotherapy of Advanced-Stage Oral Cavity Cancers

    SciTech Connect

    Lin, Chien-Yu; Wang, Hung-Ming; Kang, Chung-Jan; Lee, Li-Yu; Huang, Shiang-Fu; Fan, Kang-Hsing; Chen, Eric Yen-Chao

    2010-11-15

    Purpose: To evaluate the outcome of definitive radiotherapy (RT) for oral cavity cancers and to assess prognostic factors. Methods and Materials: Definitive RT was performed on 115 patients with oral cavity cancers at Stages III, IVA, and IVB, with a distribution of 6%, 47%, and 47%, respectively. The median dose of RT was 72Gy (range, 62-76Gy). Cisplatin-based chemotherapy was administered to 95% of the patients. Eleven patients underwent salvage surgery after RT failure. Results: Eight-eight (76.5%) patients responded partially and 23 (20%) completely; of the patients who responded, 18% and 57%, respectively, experienced a durable effect of treatment. The 3-year overall survival, disease-specific survival, and progression-free survival were 22%, 27%, and 25%, respectively. The 3-year PFS rates based on the primary tumor sites were as follows: Group I (buccal, mouth floor, and gum) 51%, Group II (retromolar and hard palate) 18%, and Group III (tongue and lip) 6% (p < 0.0001). The 3-year progression-free survival was 41% for N0 patients and 19% for patients with N+ disease (p = 0.012). The T stage and RT technique did not affect survival. The patients who underwent salvage surgery demonstrated better 3-year overall survival and disease-specific survival (53% vs. 19%, p = 0.015 and 53% vs. 24%, p = 0.029, respectively). Subsite group, N+, and salvage surgery were the only significant prognostic factors for survival after multivariate analysis. Conclusion: The primary tumor site and neck stage are prognostic predictors in advanced-stage oral cancer patients who received radical RT. The primary tumor extension and RT technique did not influence survival.

  14. Adding silver and copper to hydrogen peroxide and peracetic acid in the disinfection of an advanced primary treatment effluent.

    PubMed

    Orta De Velásquez, M T; Yáñez-Noguez, I; Jiménez-Cisneros, B; Luna Pabello, V M

    2008-11-01

    This paper evaluates the efficacy of hydrogen peroxide (HP) and peracetic acid (PAA) in the disinfection of an Advanced Primary Treatment (APT) effluent, and how said disinfection capacities can be enhanced by combining the oxidants with copper (Cu2+) and silver (Ag). The treatment sequence consisted of APT (adding chemicals to water to remove suspended solids by coagulation and flocculation), followed by disinfection with various doses of HP, HP+Cu2+, HP+Ag, PAA and PAA+Ag. Microbiological quality was determined by monitoring concentrations of fecal coliforms (FC), pathogenic bacteria (PB) and helminth eggs (HE) throughout the sequence. The results revealed that APT effluent still contains very high levels of bacteria as the treatment only removes 1-2 log of FC and PB, but the reduction in the number of viable helminth eggs was 83%. Subsequent disinfection stages demonstrated that both HP+Cu2+ and HP+Ag have a marked disinfection capacity for bacteria (3.9 and 3.4 log-inactivation, respectively). Peracetic acid on its own was already extremely efficient at disinfecting for bacteria, and the effect was enhanced when combining PAA with silver (PAA+Ag). The best result for HE removal was achieved by combining PAA with silver (PAA+Ag) at doses of 20 + 2.0 mg l(-1), respectively. The study concluded that the PAA+Ag and HP+Ag combinations were good alternatives for APT effluent disinfection, because the disinfected effluents met the standards in NOM-001-SEMARNAT-1996, Mexico's regulation governing the microbiological quality required in treated wastewater destined for unrestricted reuse in agricultural irrigation (< or =1 helminths per litre). Combining either of these disinfection treatments with a primary method such as APT, therefore, offers an effective and practical way of reducing the health risks normally associated with the reuse of wastewaters.

  15. Disinfection of an advanced primary effluent using peracetic acid or ultraviolet radiation for its reuse in public services.

    PubMed

    Julio, Flores R; Hilario, Terres-Peña; Mabel, Vaca M; Raymundo, López C; Arturo, Lizardi-Ramos; Ma Neftalí, Rojas-Valencia

    2015-03-01

    The disinfection of a continuous flow of an effluent from an advanced primary treatment (coagulation-flocculation-sedimentation) with or without posterior filtration, using either peracetic acid (PAA) or ultraviolet (UV) radiation was studied. We aimed to obtain bacteriological quality to comply with the microbiological standard established in the Mexican regulations for treated wastewater reuse (NOM-003-SEMARNAT-1997), i.e., less than 240 MPN (most probable number) FC/100 mL. The concentrations of PAA were 10, 15, and 20 mg/L, with contact times of 10, and 15 min. Fecal coliforms (FC) inactivation ranged from 0.93 up to 6.4 log units, and in all cases it reached the limits set by the mentioned regulation. Water quality influenced the PAA disinfection effectiveness. An efficiency of 91% was achieved for the unfiltered effluent, as compared to 99% when wastewater was filtered. UV radiation was applied to wastewater flows of 21, 30 and 39 L/min, with dosages from 1 to 6 mJ/cm². This treatment did not achieve the bacteriological quality required for treated wastewater reuse, since the best inactivation of FC was 1.62 log units, for a flow of 21 L/min of filtered wastewater and a UV dosage of 5.6 mJ/cm².

  16. Case report and literature review: surgical treatment of a right atrial metastatic melanoma from a previously resected "advanced" primary site with regional lymph nodes involvement.

    PubMed

    Parissis, Haralabos; Al-Alao, Bassel Suffian; Young, Vincent K

    2012-10-01

    Although melanoma of the right atrium is a rare cardiac tumor, melanoma in general has a high propensity to involve the heart. Unfortunately, however, when the tumor is involving the heart, widespread metastasis ensues and hence surgery becomes a questionable option. We report a case of a young female who presented with an advanced skin primary melanoma and regional lymph node involvement and a metastasis into the right atrium. Postoperatively tumor dissemination was controlled with adjuvant chemotherapy. A vigorous attempt aiming at tumor clearance followed by adjuvant multimodality therapy along with a tumor surveillance program may improve survival even in advanced cases.

  17. Brain Response to Primary Blast Wave Using Validated Finite Element Models of Human Head and Advanced Combat Helmet

    PubMed Central

    Zhang, Liying; Makwana, Rahul; Sharma, Sumit

    2013-01-01

    Blast-induced traumatic brain injury has emerged as a “signature injury” in combat casualty care. Present combat helmets are designed primarily to protect against ballistic and blunt impacts, but the current issue with helmets is protection concerning blasts. In order to delineate the blast wave attenuating capability of the Advanced Combat Helmet (ACH), a finite element (FE) study was undertaken to evaluate the head response against blast loadings with and without helmet using a partially validated FE model of the human head and ACH. Four levels of overpressures (0.27–0.66 MPa) from the Bowen’s lung iso-damage threshold curves were used to simulate blast insults. Effectiveness of the helmet with respect to head orientation was also investigated. The resulting biomechanical responses of the brain to blast threats were compared for human head with and without the helmet. For all Bowen’s cases, the peak intracranial pressures (ICP) in the head ranged from 0.68 to 1.8 MPa in the coup cortical region. ACH was found to mitigate ICP in the head by 10–35%. Helmeted head resulted in 30% lower average peak brain strains and product of strain and strain rate. Among three blast loading directions with ACH, highest reduction in peak ICP (44%) was due to backward blasts whereas the lowest reduction in peak ICP and brain strains was due to forward blast (27%). The biomechanical responses of a human head to primary blast insult exhibited directional sensitivity owing to the different geometry contours and coverage of the helmet construction and asymmetric anatomy of the head. Thus, direction-specific tolerances are needed in helmet design in order to offer omni-directional protection for the human head. The blasts of varying peak overpressures and durations that are believed to produce the same level of lung injury produce different levels of mechanical responses in the brain, and hence “iso-damage” curves for brain injury are likely different than the Bowen

  18. Disinfection of an advanced primary effluent with peracetic acid and ultraviolet combined treatment: a continuous-flow pilot plant study.

    PubMed

    González, Abelardo; Gehr, Ronald; Vaca, Mabel; López, Raymundo

    2012-03-01

    Disinfection of an advanced primary effluent using a continuous-flow combined peracetic acid/ultraviolet (PAA/UV) radiation system was evaluated. The purpose was to determine whether the maximum microbial content, established under Mexican standards for treated wastewaters meant for reuse--less than 240 most probable number fecal coliforms (FC)/100 mL--could be feasibly accomplished using either disinfectant individually, or the combined PAA/UV system. This meant achieving reduction of up to 5 logs, considering initial concentrations of 6.4 x 10(+6) to 5.8 x 10(+7) colony forming units/100 mL. During the tests performed under these experiments, total coliforms (TC) were counted because FC, at the most, will be equal to TC. Peracetic acid disinfection achieved less than 1.5 logs TC reduction when the C(t) x t product was less than 2.26 mg x minimum (min)/L; 3.8 logs for C(t) x t 4.40 mg x min/L; and 5.9 logs for C(t) x t 24.2 mg x min/L. In continuous-flow UV irradiation tests, at a low-operating flow (21 L/min; conditions which produced an average UV fluence of 13.0 mJ/cm2), the highest TC reduction was close to 2.5 logs. The only condition that produced a disinfection efficiency of approximately 5 logs, when both disinfection agents were used together, was the combined process dosing 30 mg PAA/L at a pilot plant flow of 21 L/min and contact time of 10 minutes to attain an average C(t) x t product of 24.2 mg x min/L and an average UV fluence of 13 mJ/cm2. There was no conclusive evidence of a synergistic effect when both disinfectants were employed in combination as compared to the individual effects achieved when used separately, but this does not take into account the nonlinearity (tailing-off) of the dose-response curve.

  19. Preliminary results of CO2 laser-assisted sclerectomy surgery (CLASS) in the treatment of advanced glaucoma in a Chinese population

    PubMed Central

    Yick, Doris W.F.; Lee, Jacky W.Y.; Tsang, Susanna; Yeung, Barry Y.M.; Yuen, Can Y.F.

    2016-01-01

    Abstract To evaluate the efficacy and safety of CO2 laser-assisted sclerectomy surgery (CLASS) in Chinese patients with advanced glaucoma. Patients with advanced glaucoma who were candidates for glaucoma filtration surgery were included. The intraocular pressure (IOP) and number of antiglaucoma medications were documented before surgery and at all postoperative clinic visits. All intra- and postoperative complications were documented. The primary outcome measures were the changes in IOP and medication use before and after the procedure as well as complications from the procedure. The secondary outcome measure included the CLASS success rate. Twenty patients (23 eyes) underwent CLASS between November 2014 and September 2015. Nineteen eyes had primary open-angle glaucoma, 2 eyes had primary angle-closure glaucoma, and 2 eyes had uveitic glaucoma. One patient was lost to follow-up. The mean age of subjects was 68.1 ± 11.9 years. IOP was significantly reduced at 1 day and 1 week after CLASS. At 6 months, the IOP and number of medications were significantly reduced by 19.0% and 38.2%, respectively (both P < 0.0001). One patient had intraoperative trabeculo-Descemet membrane perforation. Two patients required laser goniopuncture and 2 required needling between 3 and 6 months postoperatively. The overall success rate was 81.8% at 6 months. CLASS achieved a modest IOP reduction in the early postoperative period and was overall a safe procedure for advanced glaucoma. PMID:27828849

  20. Preliminary results of CO2 laser-assisted sclerectomy surgery (CLASS) in the treatment of advanced glaucoma in a Chinese population.

    PubMed

    Yick, Doris W F; Lee, Jacky W Y; Tsang, Susanna; Yeung, Barry Y M; Yuen, Can Y F

    2016-11-01

    To evaluate the efficacy and safety of CO2 laser-assisted sclerectomy surgery (CLASS) in Chinese patients with advanced glaucoma.Patients with advanced glaucoma who were candidates for glaucoma filtration surgery were included. The intraocular pressure (IOP) and number of antiglaucoma medications were documented before surgery and at all postoperative clinic visits. All intra- and postoperative complications were documented. The primary outcome measures were the changes in IOP and medication use before and after the procedure as well as complications from the procedure. The secondary outcome measure included the CLASS success rate.Twenty patients (23 eyes) underwent CLASS between November 2014 and September 2015. Nineteen eyes had primary open-angle glaucoma, 2 eyes had primary angle-closure glaucoma, and 2 eyes had uveitic glaucoma. One patient was lost to follow-up. The mean age of subjects was 68.1 ± 11.9 years. IOP was significantly reduced at 1 day and 1 week after CLASS. At 6 months, the IOP and number of medications were significantly reduced by 19.0% and 38.2%, respectively (both P < 0.0001). One patient had intraoperative trabeculo-Descemet membrane perforation. Two patients required laser goniopuncture and 2 required needling between 3 and 6 months postoperatively. The overall success rate was 81.8% at 6 months.CLASS achieved a modest IOP reduction in the early postoperative period and was overall a safe procedure for advanced glaucoma.

  1. Long-Term Outcomes After Maximal Surgical Resection and Intraoperative Electron Radiotherapy for Locoregionally Recurrent or Locoregionally Advanced Primary Renal Cell Carcinoma

    SciTech Connect

    Hallemeier, Christopher L.; Choo, Richard; Davis, Brian J.; Pisansky, Thomas M.; Gunderson, Leonard L.; Leibovich, Bradley C.; Haddock, Michael G.

    2012-04-01

    Purpose: To report outcomes of a multimodality therapy combining maximal surgical resection and intraoperative electron radiotherapy (IOERT) for patients with locoregionally (LR) recurrent renal cell carcinoma (RCC) after radical nephrectomy or LR advanced primary RCC. Methods and Materials: From 1989 through 2005, a total of 22 patients with LR recurrent (n = 19) or LR advanced primary (n = 3) RCC were treated with this multimodality approach. The median patient age was 63 years (range 46-78). Twenty-one patients (95%) received perioperative external beam radiotherapy (EBRT) with a median dose of 4,500 cGy (range, 4,140-5,500). Surgical resection was R0 (negative margins) in 5 patients (23%) and R1 (residual microscopic disease) in 17 patients (77%). The median IOERT dose delivered was 1,250 cGy (range, 1,000-2,000). Overall survival (OS) and disease-free survival (DFS) and relapse patterns were estimated using the Kaplan-Meier method. Results: The median follow-up for surviving patients was 9.9 years (range, 3.6-20 years). The OS and DFS at 1, 5, and 10 years were 91%, 40%, and 35% and 64%, 31%, and 31%, respectively. Central recurrence (within the IOERT field), LR relapse (tumor bed or regional lymph nodes), and distant metastases at 5 years were 9%, 27%, and 64%, respectively. Mortality within 30 days of surgery and IOERT was 0%. Five patients (23%) experienced acute or late National Cancer Institute Common Toxicity Criteria (NCI-CTCAE) Version 4 Grade 3 to 5 toxicities. Conclusions: In patients with LR recurrent or LR advanced primary RCC, a multimodality approach of perioperative EBRT, maximal surgical resection, and IOERT yielded encouraging results. This regimen warrants further investigation.

  2. Employing a Structured Interface to Advance Primary Students' Communicative Competence in a Text-Based Computer Mediated Environment

    ERIC Educational Resources Information Center

    Chiu, Chiung-Hui; Wu, Chiu-Yi; Hsieh, Sheng-Jieh; Cheng, Hsiao-Wei; Huang, Chung-Kai

    2013-01-01

    This study investigated whether a structured communication interface fosters primary students' communicative competence in a synchronous typewritten computer-mediated collaborative learning environment. The structured interface provided a set of predetermined utterance patterns for elementary students to use or imitate to develop communicative…

  3. Second primary cancer in survivors following concurrent chemoradiation for locally advanced non-small-cell lung cancer

    PubMed Central

    Takigawa, N; Kiura, K; Segawa, Y; Watanabe, Y; Kamei, H; Moritaka, T; Shibayama, T; Ueoka, H; Gemba, K; Yonei, T; Tabata, M; Shinkai, T; Hiraki, S; Takemoto, M; Kanazawa, S; Matsuo, K; Tanimoto, M

    2006-01-01

    Long-term cancer survivors risk development of second primary cancers (SPC). Vigilant follow-up may be required. We report outcomes of 92 patients who underwent chemoradiation for unresectable stage III non-small-cell lung cancer, with a median follow-up of 8.9 years. The incidence of SPC was 2.4 per 100 patient-years (95% confidence interval: 1.0–4.9). PMID:17031394

  4. Functional Proteomic Analysis of Advanced Serous Ovarian Cancer using Reverse Phase Protein Array: TGFβ Pathway Signaling Indicates Response to Primary Chemotherapy

    PubMed Central

    Carey, Mark S.; Agarwal, Roshan; Gilks, Blake; Swenerton, Kenneth; Kalloger, Steve; Santos, Jennifer; Ju, Zhenlin; Lu, Yiling; Zhang, Fan; Coombes, Kevin; Miller, Dianne; Huntsman, David; Mills, Gordon B.; Hennessy, Bryan T

    2010-01-01

    Purpose: Using Reverse Phase Protein Array (RPPA) we measured protein expression associated with response to primary chemotherapy in patients with advanced-stage high-grade serous ovarian cancer. Experimental Design: Tumor samples were obtained from forty-five patients with advanced high-grade serous cancers from the Gynecology Tumor Bank at the British Columbia Cancer Agency. Treatment consisted of platinum-based chemotherapy following debulking surgery. Protein lysates were prepared from fresh frozen tumor samples and 80 validated proteins from signaling pathways implicated in ovarian carcinogenesis were measured by RPPA. Normalization of Ca-125 by the 3rd cycle of chemotherapy was chosen as the primary outcome measure of chemotherapy response. Logistic regression was used for multivariate analysis to identify protein predictors of Ca-125 normalization, and Cox regression to test for the association between protein expression and PFS. A significance level of p ≤ 0.05 was used. Results: The mean age at diagnosis was 56.8 years. EGFR, YKL-40 and several TGFβ pathway proteins (c-Jun N-terminal kinase JNK, JNK phosphorylated at residues 183 and 185, PAI-1, Smad3, TAZ) showed significant associations with Ca-125 normalization on univariate testing. On multivariate analysis, EGFR (p < 0.02), JNK (p < 0.01), and Smad3 (p < 0.04) were significantly associated with normalization of Ca-125. Contingency table analysis of pathway-classified proteins revealed that the selection of TGFβ pathway proteins was unlikely due to false discovery (p < 0.007, Bonferroni-adjusted). Conclusion: TGFβ pathway signaling likely plays an important role as a marker or mediator of chemoresistance in advanced serous ovarian cancer. On this basis, future studies to develop and validate a useful predictor of treatment failure are warranted. PMID:20460476

  5. A Phase II study of acute toxicity for Celebrex{sup TM} (celecoxib) and chemoradiation in patients with locally advanced cervical cancer: Primary endpoint analysis of RTOG 0128

    SciTech Connect

    Gaffney, David K. . E-mail: david.gaffney@hci.utah.edu; Winter, Kathryn M.S.; Dicker, Adam P.; Miller, Brigitte; Eifel, Patricia J.; Ryu, Janice; Avizonis, Vilija; Fromm, Mitch; Greven, Kathryn

    2007-01-01

    Purpose: To determine treatment-related acute toxicity rates in patients with locally advanced cervical cancer treated by oral celecoxib, i.v. cisplatin and 5-FU, and concurrent pelvic radiation therapy. Methods and Materials: Eligible patients on this RTOG Phase I-II study for advanced cervix cancer included FIGO Stage IIB-IVA or patients with FIGO Stage IB through IIA with biopsy proven pelvic node metastases or tumor size {>=}5 cm. Patients were treated with pelvic radiotherapy and brachytherapy. Celecoxib was prescribed at 400 mg twice daily beginning on day 1 for 1 year. Cisplatin (75 mg/m2) and 5-FU (1g/m2 for 4 days) were administered every 3 weeks times 3. The primary end point of the study was treatment related toxicity. Results: Between August 2001 and March 2004, 84 patients were accrued to the study and 77 patients were evaluable for toxicity. Regarding the primary end point, toxicities were observed in the following areas: blood/bone marrow (16), gastrointestinal (14), pain (7), renal/genitourinary (6), cardiovascular (3), hemorrhage (1), and neurologic (1). For the first 75 evaluable patients, a toxicity failure was identified in 36 patients for a rate of 48%. Conclusions: Celecoxib at 400 mg twice daily together with concurrent cisplatin and 5-FU and pelvic radiotherapy has a high incidence of acute toxicities. The most frequent toxicities were hematologic. Albeit, the toxicity was deemed excessive in this trial, the rate of toxicities was not too different compared to other recent experiences with concurrent chemoradiation for advanced cervix cancer.

  6. Interfraction Displacement of Primary Tumor and Involved Lymph Nodes Relative to Anatomic Landmarks in Image Guided Radiation Therapy of Locally Advanced Lung Cancer

    SciTech Connect

    Jan, Nuzhat; Balik, Salim; Hugo, Geoffrey D.; Mukhopadhyay, Nitai; Weiss, Elisabeth

    2014-01-01

    Purpose: To analyze primary tumor (PT) and lymph node (LN) position changes relative to each other and relative to anatomic landmarks during conventionally fractionated radiation therapy for patients with locally advanced lung cancer. Methods and Materials: In 12 patients with locally advanced non-small cell lung cancer PT, LN, carina, and 1 thoracic vertebra were manually contoured on weekly 4-dimensional fan-beam CT scans. Systematic and random interfraction displacements of all contoured structures were identified in the 3 cardinal directions, and resulting setup margins were calculated. Time trends and the effect of volume changes on displacements were analyzed. Results: Three-dimensional displacement vectors and systematic/random interfraction displacements were smaller for carina than for vertebra both for PT and LN. For PT, mean (SD) 3-dimensional displacement vectors with carina-based alignment were 7 (4) mm versus 9 (5) mm with bony anatomy (P<.0001). For LN, smaller displacements were found with carina- (5 [3] mm, P<.0001) and vertebra-based (6 [3] mm, P=.002) alignment compared with using PT for setup (8 [5] mm). Primary tumor and LN displacements relative to bone and carina were independent (P>.05). Displacements between PT and bone (P=.04) and between PT and LN (P=.01) were significantly correlated with PT volume regression. Displacements between LN and carina were correlated with LN volume change (P=.03). Conclusions: Carina-based setup results in a more reproducible PT and LN alignment than bony anatomy setup. Considering the independence of PT and LN displacement and the impact of volume regression on displacements over time, repeated CT imaging even with PT-based alignment is recommended in locally advanced disease.

  7. Advancing survivorship care through the National Cancer Survivorship Resource Center: developing American Cancer Society guidelines for primary care providers.

    PubMed

    Cowens-Alvarado, Rebecca; Sharpe, Katherine; Pratt-Chapman, Mandi; Willis, Anne; Gansler, Ted; Ganz, Patricia A; Edge, Stephen B; McCabe, Mary S; Stein, Kevin

    2013-05-01

    The National Cancer Survivorship Resource Center (The Survivorship Center) began in 2010 as a collaboration between the American Cancer Society and the George Washington University Cancer Institute and was funded by the Centers for Disease Control and Prevention. The Survivorship Center aims to improve the overall health and quality of life of posttreatment cancer survivors. One key to addressing the needs of this ever-growing population is to develop clinical follow-up care guidelines that emphasize not only the importance of surveillance for cancer recurrence, but also address the assessment and management of the physical and psychosocial long-term and late effects that may result from having cancer and undergoing cancer treatment as well as highlight the importance of healthy behaviors that can reduce the risk of cancer recurrence, second primary cancers, and other chronic diseases. Currently, The Survivorship Center is coordinating the work of experts in oncology, primary care, and other health care professions to develop follow-up care guidelines for 10 priority cancer sites.

  8. Platinum-based Chemotherapy in Primary Advanced Seminoma—a Retrospective Analysis: Treatment Results at the Northern Israel Oncology Center (1989–2010)

    PubMed Central

    Stein, Moshe E.; Drumea, Karen; Charas, Tomer; Gershuny, Anthony; Ben-Yosef, Rahamim

    2014-01-01

    Objective: Over the past 30 years, great strides have been made in the treatment of disseminated testicular tumors. Despite the low number of patients and the rarity of studies concerning primary advanced seminoma, the efficacy of chemotherapy is clear, mainly 3–4-cisplatin-based chemotherapy. Aiming to contribute to the understanding and implementation of proper chemotherapeutic management in advanced seminoma patients, we retrospectively summarized our experience with 26 patients who were referred for platinum-based chemotherapy, post-orchiectomy to the Northern Israel Oncology Center between 1989 and 2010. Response rate, side effects, and long-term outcome were investigated. Methods: Before chemotherapy, meticulous staging was done, including tumor markers (B-human chorionic gonadotropin (B-HCG), alpha-fetoprotein (AFP), and lactic dehydrogenase (LDH)), and abdominal and pelvic computerized tomography (CT) scans were carried out. Results: All 26 treated patients achieved complete remission, clinically and symptomatically, with normalization of their CT scans. At a median follow-up of 120 months (range, 24–268 months) all patients are alive, without evidence of recurrent disease. One patient whose disease recurred twice achieved a third complete remission following salvage treatment with high-dose chemotherapy and autologous peripheral stem cell transplantation. Another patient, who preferred surveillance, relapsed abdominally after 9 months but achieved long-standing complete remission with cisplatin-based chemotherapy. Both these patients are alive with no evidence of disease. Three patients recovered uneventfully from bleomycin-induced pneumonitis. Conclusions: Advanced seminoma is a highly curable disease using platinum-based chemotherapy. Our study confirms the efficacy and safety of cisplatin-based chemotherapy in the treatment of advanced seminoma. PMID:24498512

  9. Primary Tumor Necrosis Predicts Distant Control in Locally Advanced Soft-Tissue Sarcomas After Preoperative Concurrent Chemoradiotherapy

    SciTech Connect

    MacDermed, Dhara M.; Miller, Luke L.; Peabody, Terrance D.; Simon, Michael A.; Luu, Hue H.; Haydon, Rex C.; Montag, Anthony G.; Undevia, Samir D.

    2010-03-15

    Purpose: Various neoadjuvant approaches have been evaluated for the treatment of locally advanced soft-tissue sarcomas. This retrospective study describes a uniquely modified version of the Eilber regimen developed at the University of Chicago. Methods and Materials: We treated 34 patients (28 Stage III and 6 Stage IV) with locally advanced soft-tissue sarcomas of an extremity between 1995 and 2008. All patients received preoperative therapy including ifosfamide (2.5 g/m2 per day for 5 days) with concurrent radiation (28 Gy in 3.5-Gy daily fractions), sandwiched between various chemotherapy regimens. Postoperatively, 47% received further adjuvant chemotherapy. Results: Most tumors (94%) were Grade 3, and all were T2b, with a median size of 10.3 cm. Wide excision was performed in 29 patients (85%), and 5 required amputation. Of the resected tumor specimens, 50% exhibited high (>=90%) treatment-induced necrosis and 11.8% had a complete pathologic response. Surgical margins were negative in all patients. The 5-year survival rate was 42.3% for all patients and 45.2% for Stage III patients. For limb-preservation patients, the 5-year local control rate was 89.0% and reoperation was required for wound complications in 17.2%. The 5-year freedom-from-distant metastasis rate was 53.4% (Stage IV patients excluded), and freedom from distant metastasis was superior if treatment-induced tumor necrosis was 90% or greater (84.6% vs. 19.9%, p = 0.02). Conclusions: This well-tolerated concurrent chemoradiotherapy approach yields excellent rates of limb preservation and local control. The resulting treatment-induced necrosis rates are predictive of subsequent metastatic risk, and this information may provide an opportunity to guide postoperative systemic therapies.

  10. Advanced composites structural concepts and materials technologies for primary aircraft structures. Structural response and failure analysis: ISPAN modules users manual

    NASA Technical Reports Server (NTRS)

    Hairr, John W.; Huang, Jui-Ten; Ingram, J. Edward; Shah, Bharat M.

    1992-01-01

    The ISPAN Program (Interactive Stiffened Panel Analysis) is an interactive design tool that is intended to provide a means of performing simple and self contained preliminary analysis of aircraft primary structures made of composite materials. The program combines a series of modules with the finite element code DIAL as its backbone. Four ISPAN Modules were developed and are documented. These include: (1) flat stiffened panel; (2) curved stiffened panel; (3) flat tubular panel; and (4) curved geodesic panel. Users are instructed to input geometric and material properties, load information and types of analysis (linear, bifurcation buckling, or post-buckling) interactively. The program utilizing this information will generate finite element mesh and perform analysis. The output in the form of summary tables of stress or margins of safety, contour plots of loads or stress, and deflected shape plots may be generalized and used to evaluate specific design.

  11. Primary Tumor Volume Is an Important Predictor of Clinical Outcomes Among Patients With Locally Advanced Squamous Cell Cancer of the Head and Neck Treated With Definitive Chemoradiotherapy

    SciTech Connect

    Strongin, Anna; Yovino, Susannah; Taylor, Rodney; Wolf, Jeffrey; Cullen, Kevin; Zimrin, Ann; Strome, Scott; Regine, William; Suntharalingam, Mohan

    2012-04-01

    Purpose: The tumor volume has been established as a significant predictor of outcomes among patients with head-and-neck cancer undergoing radiotherapy alone. The present study attempted to add to the existing data on tumor volume as a prognostic factor among patients undergoing chemoradiotherapy. Methods and Materials: A total of 78 patients who had undergone definitive chemoradiotherapy for Stage III-IV squamous cell cancer of the hypopharynx, oropharynx, and larynx were identified. The primary tumor volumes were calculated from the treatment planning computed tomography scans, and these were correlated to the survival and tumor control data obtained from the retrospective analysis. Results: The interval to progression correlated with the primary tumor volume (p = .007). The critical cutoff point for the tumor volume was identified as 35 cm{sup 3}, and patients with a tumor volume <35 cm{sup 3} had a significantly better prognosis than those with a tumor volume >35 cm{sup 3} at 5 years (43% vs. 71%, p = .010). Longer survival was also correlated with smaller primary tumor volumes (p = .022). Similarly, patients with a primary tumor volume <35 cm{sup 3} had a better prognosis in terms of both progression-free survival (61% vs. 33%, p = .004) and overall survival (84% vs. 41%, p = < .001). On multivariate analysis, the primary tumor volume was the best predictor of recurrence (hazard ratio 4.7, 95% confidence interval 1.9-11.6; p = .001) and survival (hazard ratio 10.0, 95% confidence interval 2.9-35.1; p = < .001). In contrast, the T stage and N stage were not significant factors. Analysis of variance revealed that tumors with locoregional failure were on average 21.6 cm{sup 3} larger than tumors without locoregional failure (p = .028) and 27.1-cm{sup 3} larger than tumors that recurred as distant metastases (p = .020). Conclusion: The results of our study have shown that the primary tumor volume is a significant prognostic factor in patients with advanced cancer

  12. Advanced approach to build the design space for the primary drying of a pharmaceutical freeze-drying process.

    PubMed

    Fissore, Davide; Pisano, Roberto; Barresi, Antonello A

    2011-11-01

    This paper deals with the design space of a pharmaceutical freeze-drying process. Mathematical modeling is used to investigate the effect of the operating conditions [shelf temperature (T(shelf)) and chamber pressure (P(c))] on product temperature (that has to remain below a limit value) and sublimation flux (that has to be lower than a level that would cause choked flow). The algorithm takes into account the variation of the design space with time due to the increase in the dried layer thickness. Besides T(shelf) and P(c), the dried layer thickness is used as the third coordinate of the diagram, thus resulting in just one graph that can be used to build recipes with variable operating conditions, as well as to analyze the effect of process failures. Such results are compared with those obtained when the variation of the design space with time is not accounted for; in this case, the design space comprises those operating conditions that fulfill the operation constraints throughout primary drying, thus giving a much more conservative recipe when designing the process or potentially misleading results when analyzing process failures. Finally, the proposed method has been used to design, and experimentally validate, a recipe for a pharmaceutical formulation.

  13. Primary chemotherapy with gemcitabine, liposomal doxorubicin and docetaxel in patients with locally advanced breast cancer: results of a phase I trial.

    PubMed

    Schmid, Peter; Krocker, Jutta; Schulz, Carsten-Oliver; Michniewicz, Katarzyna; Dieing, Annette; Eggemann, Holm; Heilmann, Volker; Blohmer, Jens-Uwe; Sezer, Orhan; Elling, Dirk; Possinger, Kurt

    2005-01-01

    The primary objective was to determine the optimal doses for gemcitabine (prolonged infusion), liposomal doxorubicin (Myocet) and docetaxel as primary (neoadjuvant) chemotherapy for locally advanced breast cancer. Secondary objectives included evaluation of the safety and efficacy of the regimen. Patients (n=19) with histologically confirmed stage II or III breast cancer were treated with liposomal doxorubicin (50-60 mg/m2) and docetaxel (60-75 mg/m2) on day 1, and gemcitabine as 4-h infusion (350-400 mg/m2) on day 4. Treatment was repeated every 3 weeks for a maximum of 6 cycles. The maximum tolerated doses were gemcitabine 350 mg/m2, liposomal doxorubicin 60 mg/m2 and docetaxel 75 mg/m2. Dose-limiting toxicities were stomatitis, diarrhea and infection. The predominant hematologic toxicity was mild-to-moderate myelosuppression with grade 3/4 neutropenia in 20% of cycles. Non-hematologic toxicity was generally mild, with no grade 4 toxicities being observed. Predominant non-hematologic toxicity was stomatitis, which occurred in 95% of patients. Grade 3 toxicities were reported for stomatitis, nausea, diarrhea, infection and constipation. No cases of cardiac, renal, pulmonary or neurotoxicity were observed. The clinical response rate was 83% and histologically confirmed, clinically complete remissions occurred in two patients (11%). We conclude that the combination of gemcitabine (prolonged infusion), liposomal doxorubicin and docetaxel is safe and highly effective in patients with locally advanced breast cancer as defined by maximum tolerated doses. The evaluated schedule is suitable for phase II studies.

  14. Nurse Mentors to Advance Quality Improvement in Primary Health Centers: Lessons From a Pilot Program in Northern Karnataka, India

    PubMed Central

    Fischer, Elizabeth A; Jayana, Krishnamurthy; Cunningham, Troy; Washington, Maryann; Mony, Prem; Bradley, Janet; Moses, Stephen

    2015-01-01

    High-quality care during labor, delivery, and the postpartum period is critically important since maternal and child morbidity and mortality are linked to complications that arise during these stages. A nurse mentoring program was implemented in northern Karnataka, India, to improve quality of services at primary health centers (PHCs), the lowest level in the public health system that offers basic obstetric care. The intervention, conducted between August 2012 and July 2014, employed 53 full-time nurse mentors and was scaled-up in 385 PHCs in 8 poor rural districts. Each mentor was responsible for 6 to 8 PHCs and conducted roughly 6 mentoring visits per PHC in the first year. This paper reports the results of a qualitative inquiry, conducted between September 2012 and April 2014, assessing the program's successes and challenges from the perspective of mentors and PHC teams. Data were gathered through 13 observations, 9 focus group discussions with mentors, and 25 individual and group interviews with PHC nurses, medical officers, and district health officers. Mentors and PHC staff and leaders reported a number of successes, including development of rapport and trust between mentors and PHC staff, introduction of team-based quality improvement processes, correct and consistent use of a new case sheet to ensure adherence to clinical guidelines, and increases in staff nurses’ knowledge and skills. Overall, nurses in many PHCs reported an increased ability to provide care according to guidelines and to handle maternal and newborn complications, along with improvements in equipment and supplies and referral management. Challenges included high service delivery volumes and/or understaffing at some PHCs, unsupportive or absent PHC leadership, and cultural practices that impacted quality. Comprehensive mentoring can build competence and improve performance by combining on-the-job clinical and technical support, applying quality improvement principles, and promoting team

  15. Nurse Mentors to Advance Quality Improvement in Primary Health Centers: Lessons From a Pilot Program in Northern Karnataka, India.

    PubMed

    Fischer, Elizabeth A; Jayana, Krishnamurthy; Cunningham, Troy; Washington, Maryann; Mony, Prem; Bradley, Janet; Moses, Stephen

    2015-12-01

    High-quality care during labor, delivery, and the postpartum period is critically important since maternal and child morbidity and mortality are linked to complications that arise during these stages. A nurse mentoring program was implemented in northern Karnataka, India, to improve quality of services at primary health centers (PHCs), the lowest level in the public health system that offers basic obstetric care. The intervention, conducted between August 2012 and July 2014, employed 53 full-time nurse mentors and was scaled-up in 385 PHCs in 8 poor rural districts. Each mentor was responsible for 6 to 8 PHCs and conducted roughly 6 mentoring visits per PHC in the first year. This paper reports the results of a qualitative inquiry, conducted between September 2012 and April 2014, assessing the program's successes and challenges from the perspective of mentors and PHC teams. Data were gathered through 13 observations, 9 focus group discussions with mentors, and 25 individual and group interviews with PHC nurses, medical officers, and district health officers. Mentors and PHC staff and leaders reported a number of successes, including development of rapport and trust between mentors and PHC staff, introduction of team-based quality improvement processes, correct and consistent use of a new case sheet to ensure adherence to clinical guidelines, and increases in staff nurses' knowledge and skills. Overall, nurses in many PHCs reported an increased ability to provide care according to guidelines and to handle maternal and newborn complications, along with improvements in equipment and supplies and referral management. Challenges included high service delivery volumes and/or understaffing at some PHCs, unsupportive or absent PHC leadership, and cultural practices that impacted quality. Comprehensive mentoring can build competence and improve performance by combining on-the-job clinical and technical support, applying quality improvement principles, and promoting team

  16. Structural and functional brain changes beyond visual system in patients with advanced glaucoma.

    PubMed

    Frezzotti, Paolo; Giorgio, Antonio; Motolese, Ilaria; De Leucio, Alessandro; Iester, Michele; Motolese, Eduardo; Federico, Antonio; De Stefano, Nicola

    2014-01-01

    In order to test the hypothesis that in primary open angle glaucoma (POAG), an important cause of irreversible blindness, a spreading of neurodegeneration occurs through the brain, we performed multimodal MRI and subsequent whole-brain explorative voxelwise analyses in 13 advanced POAG patients and 12 age-matched normal controls (NC). Altered integrity (decreased fractional anisotropy or increased diffusivities) of white matter (WM) tracts was found not only along the visual pathway of POAG but also in nonvisual WM tracts (superior longitudinal fascicle, anterior thalamic radiation, corticospinal tract, middle cerebellar peduncle). POAG patients also showed brain atrophy in both visual cortex and other distant grey matter (GM) regions (frontoparietal cortex, hippocampi and cerebellar cortex), decreased functional connectivity (FC) in visual, working memory and dorsal attention networks and increased FC in visual and executive networks. In POAG, abnormalities in structure and FC within and outside visual system correlated with visual field parameters in the poorer performing eyes, thus emphasizing their clinical relevance. Altogether, this represents evidence that a vision disorder such as POAG can be considered a widespread neurodegenerative condition.

  17. Matched Survival Analysis in Patients With Locoregionally Advanced Resectable Oropharyngeal Carcinoma: Platinum-Based Induction and Concurrent Chemoradiotherapy Versus Primary Surgical Resection

    SciTech Connect

    Boscolo-Rizzo, Paolo; Gava, Alessandro; Baggio, Vittorio; Marchiori, Carlo; Stellin, Marco; Fuson, Roberto; Lamon, Stefano; Da Mosto, Maria Cristina

    2011-05-01

    Purpose: The outcome of a prospective case series of 47 patients with newly diagnosed resectable locoregionally advanced oropharyngeal squamous cell carcinoma treated with platinum-based induction-concurrent chemoradiotherapy (IC/CCRT) was compared with the outcome of 47 matched historical control patients treated with surgery and postoperative RT. Methods and Materials: A total of 47 control patients with locoregionally advanced oropharyngeal squamous cell carcinoma were identified from review of a prospectively compiled comprehensive computerized head-and-neck cancer database and were matched with a prospective case series of patients undergoing IC/CCRT by disease stage, nodal status, gender, and age ({+-}5 years). The IC/CCRT regimen consisted of one cycle of induction chemotherapy followed by conventionally fractionated RT to a total dose of 66-70 Gy concomitantly with two cycles of chemotherapy. Each cycle of chemotherapy consisted of cisplatinum, 100 mg/m{sup 2}, and a continuous infusion of 5-fluorouracil, 1,000 mg/m{sup 2}/d for 5 days. The survival analysis was performed using Kaplan-Meier estimates. Matched-pair survival was compared using the Cox proportional hazards model. Results: No significant difference was found in the overall survival or progression-free survival rates between the two groups. The matched analysis of survival did not show a statistically significant greater hazard ratio for overall death (hazard ratio, 1.35; 95% confidence interval, 0.65-2.80; p = .415) or progression (hazard ratio, 1.44; 95% confidence interval, 0.72-2.87; p = .301) for patients undergoing IC/CCRT. Conclusion: Although the sample size was small and not randomized, this matched-pair comparison between a prospective case series and a historical cohort treated at the same institution showed that the efficacy of IC/CCRT with salvage surgery is as good as primary surgical resection and postoperative RT.

  18. Factors associated with the use of advanced practice nurses/physician assistants in a fee-for-service nursing home practice: a comparison with primary care physicians.

    PubMed

    Bakerjian, Debra; Harrington, Charlene

    2012-07-01

    The purpose of this research was to examine factors associated with the use of advanced practice nurse and physician assistant (APN/PA) visits to nursing home (NH) patients compared with those by primary care physicians (PCPs). This was a secondary analysis using Medicare claims data. General estimation equations were used to determine the odds of NH residents receiving APN/PA visits. Ordinary least squares analyses were used to examine factors associated with these visits. A total of 5,436 APN/PAs provided care to 27% of 129,812 residents and were responsible for 16% of the 1.1 million Medicare NH fee-for-service visits in 2004. APN/PAs made an average of 33 visits annually compared with PCPs (21 visits). Neuropsychiatric and acute diagnoses and patients with a long-stay status were associated with more APN/PA visits. APN/PAs provide a substantial amount of care, but regional variations occur, and Medicare regulations constrain the ability of APN/PAs to substitute for physician visits.

  19. The use of ozone during advanced primary treatment of wastewater for its reuse in agriculture: an approach to enhance coagulation, disinfection and crop productivities.

    PubMed

    Campos-Reales-Pineda, A E; Orta de Velásquez, M T; Rojas-Valencia, M N

    2008-01-01

    The purpose of this work was to evaluate the effect that ozone (O(3)) has on the advanced primary treatment (APT) and disinfection of wastewaters for their reuse in agriculture. The enhancement and optimization of APT was done by applying low O(3) doses during coagulation. By applying an ozone dose of 2 mg/L during APT, the required coagulant dose may be reduced by up to 25% to achieve a similar turbidity removal (and up to 50% for total suspended solids removal), when compared to a conventional APT treatment. When the same coagulant dose was applied (60 mg/L), the volume of settleable solids was reduced from 31.0 to 25.5 mL/L, and the settling velocity increased from 0.111 to 0.139 m/min. Disinfection was also improved by the use of ozone, which leads to better plant germination rates than when using chlorination, because of reduced toxicity of the ozonated effluents. Additionally, helminth eggs content was reduced by applying ozone.

  20. Primary hyperparathyroidism

    PubMed Central

    Madkhali, Tarıq; Alhefdhi, Amal; Chen, Herbert; Elfenbein, Dawn

    2016-01-01

    Primary hyperparathyroidism is a common endocrine disorder caused by overactivation of parathyroid glands resulting in excessive release of parathyroid hormone. The resultant hypercalcemia leads to a myriad of symptoms. Primary hyperparathyroidism may increase a patient’s morbidity and even mortality if left untreated. During the last few decades, disease presentation has shifted from the classic presentation of severe bone and kidney manifestations to most patients now being diagnosed on routine labs. Although surgery is the only curative therapy, many advances have been made over the past decades in the diagnosis and the surgical management of primary hyperparathyroidism. The aim of this review is to summarize the characteristics of the disease, the work up, and the treatment options. PMID:26985167

  1. Evaluation of disinfection techniques in the treatment of advanced primary treated wastewater for Ciudad Juárez, México.

    PubMed

    Carrasco, Leirad; Turner, Charles D

    2006-01-01

    The purpose of this study was to develop and evaluate the effectiveness of alternative disinfection techniques at the bench-scale level using wastewater from Ciudad Juarez, Mexico, as model feed. This paper presents findings on the effectiveness of UV radiation, peracetic acid (PAA), chlorine dioxide (ClO2), and hypochlorous acid (HOCl) as disinfectants for advanced primary treatment (APT) plant effluent. Wastewater samples for bench-scale testing were collected from an agua negra ("black water") ditch that is part of the combined sewer system in Ciudad Juarez. Bench-scale simulations of the APT process used in Ciudad Juarez were run using a jar test apparatus and aluminum sulfate [Al2(SO4)3] as the coagulant. Jar test effluent from the bench system was used for disinfection testing. The Mexican discharge quality standard for total coliforms is 10 000/100 mL. Ultraviolet radiation met this standard at a dose of 47.5 mW-s/cm2. Ultraviolet disinfection proved reliable and effective despite the presence of suspended solids, and UV dose effectiveness expressed as a total coliforms survival ratio was best explained by a linear regression model. The ClO2 dose ranged from 10 to 20 mg/L and was only effective under ambient temperature conditions found during the winter months; PAA disinfection never met Mexican standards. Chlorine disinfection was effective at a dose range of 8 to 10 mg/L on samples collected at low temperature conditions. Since the completion of this research, Ciudad Juarez has discontinued the use of chlorine disinfection because of its high cost and ineffectiveness.

  2. Advanced glycation end products promote the proliferation and migration of primary rat vascular smooth muscle cells via the upregulation of BAG3.

    PubMed

    Li, Cunshu; Chang, Ye; Li, Yuan; Chen, Shuang; Chen, Yintao; Ye, Ning; Dai, Dongxue; Sun, Yingxian

    2017-03-28

    The present study was aimed to investigate the role of reactive oxygen species (ROS) on advanced glycation end product (AGE)-induced proliferation and migration of vascular smooth muscle cells (VSMCs) and whether Bcl-2‑associated athanogene 3 (BAG3) is involved in the process. Primary rat VSMCs were extracted and cultured in vitro. Cell viability was detected by MTT assay and cell proliferation was detected by EdU incorporation assay. Cell migration was detected by wound healing and Transwell assays. BAG3 was detected using qPCR and western blot analysis. Transcriptional and translational inhibitors (actinomycin D and cycloheximide, respectively) were used to study the effect of AGEs on the expression of BAG3 in VSMCs. Lentiviral plasmids containing short hairpin RNA (shRNA) against rat BAG3 or control shRNA were transduced into VSMCs. Cellular ROS were detected by 2',7'-dichlorofluorescein diacetate (DCFH-DA) staining. Mitochondrial membrane potential was detected by tetramethylrhodamine methyl ester (TMRE) staining. AGEs significantly increased the expression of BAG3 in a dose-and time-dependent manner. Furthermore, AGEs mainly increased the expression of BAG3 mRNA by increasing the RNA synthesis rather than inhibiting the RNA translation. BAG3 knockdown reduced the proliferation and migration of VSMCs induced by AGEs. BAG3 knockdown reduced the generation of ROS and sustained the mitochondrial membrane potential of VSMCs. Reduction of ROS production by N-acetylcysteine (NAC), a potent antioxidant, also reduced the proliferation and migration of VSMCs. On the whole, the present study demonstrated for the first time that AGEs could increase ROS production and promote the proliferation and migration of VSMCs by upregulating BAG3 expression. This study indicated that BAG3 should be considered as a potential target for the prevention and/or treatment of vascular complications of diabetes.

  3. [Primary hyperoxaluria].

    PubMed

    Cochat, Pierre; Fargue, Sonia; Bacchetta, Justine; Bertholet-Thomas, Aurélia; Sabot, Jean-François; Harambat, Jérôme

    2011-07-01

    Primary hyperoxalurias are rare recessive inherited inborn errors of glyoxylate metabolism. They are responsible for progressive renal involvement, which further lead to systemic oxalate deposition, which can even occur in infants. Primary hyperoxaluria type 1 is the most common form in Europe and is due to alanine-glyoxylate aminostransferase deficiency, a hepatic peroxisomal pyridoxin-dependent enzyme. Therefore primary hyperoxaluria type 1 is responsible for hyperoxaluria leading to aggressive stone formation and nephrocalcinosis. As glomerular filtration rate decreases, systemic oxalate storage occurs throughout all the body, and mainly in the skeleton. The diagnosis is first based on urine oxalate measurement, then on genotyping, which may also allow prenatal diagnosis to be proposed. Conservative measures - including hydration, crystallization inhibitors and pyridoxine - are safe and may allow long lasting renal survival, provided it is given as soon as the diagnosis has been even suspected. No dialysis procedure can remove enough oxalate to compensate oxalate overproduction from the sick liver, therefore a combined liver and kidney transplantation should be planned before advanced renal disease has occurred, in order to limit/avoid systemic oxalate deposition. In the future, primary hyperoxaluria type 1 may benefit from hepatocyte transplantation, chaperone molecules, etc.

  4. Talazoparib and HSP90 Inhibitor AT13387 in Treating Patients With Metastatic Advanced Solid Tumor or Recurrent Ovarian, Fallopian Tube, Primary Peritoneal, or Triple Negative Breast Cancer

    ClinicalTrials.gov

    2016-07-22

    Adult Solid Neoplasm; Estrogen Receptor Negative; Fallopian Tube Serous Neoplasm; HER2/Neu Negative; Ovarian Serous Adenocarcinoma; Ovarian Serous Tumor; Primary Peritoneal Serous Adenocarcinoma; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Triple-Negative Breast Carcinoma

  5. Carboplatin, Gemcitabine Hydrochloride, and Mifepristone in Treating Patients With Advanced Breast Cancer or Recurrent or Persistent Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2016-12-28

    Male Breast Cancer; Recurrent Breast Cancer; Recurrent Fallopian Tube Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Primary Peritoneal Cavity Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

  6. Changes in the contralateral eye in uncomplicated persistent hyperplastic primary vitreous in adults.

    PubMed

    Awan, K J; Humayun, M

    1985-02-15

    In two adults (a 62-year-old man and a 71-year-old woman) uncomplicated full-blown unilateral persistent hyperplastic primary vitreous was diagnosed on the basis of characteristic clinical features and ultrasonography. In the contralateral uninvolved eyes, we found open-angle glaucoma, anomalous blood vessels along the entire circumference of the anterior chamber angle, band keratopathy, and heterochromia iridis. The axial length of one involved eye was about 0.85 mm larger than that of the uninvolved eye.

  7. Primary Hyperparathyroidism

    PubMed Central

    Bandeira, Leonardo; Bilezikian, John

    2016-01-01

    Over the past several generations, primary hyperparathyroidism (PHTP) has undergone a change in its clinical presentation in many countries from a symptomatic disease to an asymptomatic one. The reasons for this change in clinical presentation are related to the widespread use of biochemical screening tests, to the measurement of PTH more routinely in the evaluation of metabolic bone disease and to the status of vitamin D sufficiency in the population. Along with recognition of a broader clinical spectrum of disease, including a more recently recognized normocalcemic variant, has come an appreciation that the evaluation of classic target organs that can be affected in PHPT, such as the skeleton and the kidneys, require more advanced imaging technology for complete evaluation. It is clear that even in asymptomatic patients, evidence for microstructural disease in the skeleton and calcifications in the kidneys can be demonstrated often. Potential non-classical manifestations of PHPT related to neurocognition and the cardiovascular system continue to be of interest. As a result of these advances, revised guidelines for the management of asymptomatic PHPT have been recently published to help the clinician determine whether surgery is appropriate or whether a more conservative approach is acceptable. PMID:27508075

  8. Community-based medical systems advancement in a hospital-primary health care centre in Crete, Greece: concepts, methods, and the new role of the general practitioner.

    PubMed

    Chatziarsenis, M; Lionis, C; Faresjö, T; Fioretos, M; Trell, E

    1998-06-01

    Modern health systems research and development emphasize the transition from hospital to primary health care. Importantly, this transition is projected to be coordinated and interactive, as facilitated, e.g., by improved information systems and collaboration between the involved parties, including Universities and health authorities. An ideal combination of this might accordingly be offered by a synthesis of a basic hospital and primary health care center in an area of suitable site, size, and structure. We believe that our institution, Nosokomion Neapolis, in; the moderate-size Cretan township of Neapolis (New-city) offers an interesting model example of this, because of its affiliation with the University of Heraklion and its international and EU-supported project status. In the present report we want to emphasize the elements that are particularly well suited and manageable and in many ways both opportunistic and conscientious "back to the future" instances of a successful Hospital/Primary Health Care integration. Specifically, we think that the advantages in local area epidemiology, prevention, and quality assurance are apparent, and nurture a--rather renewed that new-role of the general practitioner as both a holistic population doctor and a health systems researcher for the year 2,000 and beyond.

  9. Body-mass index and risk of advanced chronic kidney disease: Prospective analyses from a primary care cohort of 1.4 million adults in England

    PubMed Central

    Bankhead, Clare; Matsushita, Kunihiro; Stevens, Sarah; Holt, Tim; Hobbs, F. D. Richard; Coresh, Josef; Woodward, Mark

    2017-01-01

    Background It is uncertain whether being overweight, but not obese, is associated with advanced chronic kidney disease (CKD) and how the size and shape of associations between body-mass index (BMI) and advanced CKD differs among different types of people. Methods We used Clinical Practice Research Datalink records (2000–2014) with linkage to English secondary care and mortality data to identify a prospective cohort with at least one BMI measure. Cox models adjusted for age, sex, smoking and social deprivation and subgroup analyses by diabetes, hypertension and prior cardiovascular disease assessed relationships between BMI and CKD stages 4–5 and end-stage renal disease (ESRD). Findings 1,405,016 adults aged 20–79 with mean BMI 27.4kg/m2 (SD 5.6) were followed for 7.5 years. Compared to a BMI of 20 to <25kg/m2, higher BMI was associated with a progressively increased risk of CKD stages 4–5 (hazard ratio 1.34, 95% CI 1.30–1.38 for BMI 25 to <30kg/m2; 1.94, 1.87–2.01 for BMI 30 to <35kg/m2; and 3.10, 2.95–3.25 for BMI ≥35kg/m2). The association between BMI and ESRD was shallower and reversed at low BMI. Current smoking, prior diabetes, hypertension or cardiovascular disease all increased risk of CKD, but the relative strength and shape of BMI-CKD associations, which were generally log-linear above a BMI of 25kg/m2, were similar among those with and without these risk factors. There was direct evidence that being overweight was associated with increased risk of CKD stages 4–5 in these subgroups. Assuming causality, since 2000 an estimated 39% (36–42%) of advanced CKD in women and 26% (22–30%) in men aged 40–79 resulted from being overweight or obese. Conclusions This study provides direct evidence that being overweight increases risk of advanced CKD, that being obese substantially increases such risk, and that this remains true for those with and without diabetes, hypertension or cardiovascular disease. Strategies to reduce weight among those

  10. The prognostic implication of the expression of EGFR, p53, cyclin D1, Bcl-2 and p16 in primary locally advanced oral squamous cell carcinoma cases: a tissue microarray study.

    PubMed

    Solomon, Monica Charlotte; Vidyasagar, M S; Fernandes, Donald; Guddattu, Vasudev; Mathew, Mary; Shergill, Ankur Kaur; Carnelio, Sunitha; Chandrashekar, Chetana

    2016-12-01

    Oral squamous cell carcinomas comprise a heterogeneous tumor cell population with varied molecular characteristics, which makes prognostication of these tumors a complex and challenging issue. Thus, molecular profiling of these tumors is advantageous for an accurate prognostication and treatment planning. This is a retrospective study on a cohort of primary locally advanced oral squamous cell carcinomas (n = 178) of an Indian rural population. The expression of EGFR, p53, cyclin D1, Bcl-2 and p16 in a cohort of primary locally advanced oral squamous cell carcinomas was evaluated. A potential biomarker that can predict the tumor response to treatment was identified. Formalin-fixed paraffin-embedded tumor blocks of (n = 178) of histopathologically diagnosed cases of locally advanced oral squamous cell carcinomas were selected. Tissue microarray blocks were constructed with 2 cores of 2 mm diameter from each tumor block. Four-micron-thick sections were cut from these tissue microarray blocks. These tissue microarray sections were immunohistochemically stained for EGFR, p53, Bcl-2, cyclin D1 and p16. In this cohort, EGFR was the most frequently expressed 150/178 (84%) biomarker of the cases. Kaplan-Meier analysis showed a significant association (p = 0.038) between expression of p53 and a poor prognosis. A Poisson regression analysis showed that tumors that expressed p53 had a two times greater chance of recurrence (unadjusted IRR-95% CI 2.08 (1.03, 4.5), adjusted IRR-2.29 (1.08, 4.8) compared with the tumors that did not express this biomarker. Molecular profiling of oral squamous cell carcinomas will enable us to categorize our patients into more realistic risk groups. With biologically guided tumor characterization, personalized treatment protocols can be designed for individual patients, which will improve the quality of life of these patients.

  11. Preliminary report of a new treatment strategy for advanced pelvic malignancy: surgical resection and radiation therapy using afterloading catheters plus an inflatable displacement prosthesis in the treatment of advanced primary and recurrent rectal cancer

    SciTech Connect

    Edington, H.D.; Hancock, S.; Coe, F.L.; Sugarbaker, P.H.

    1986-09-01

    An unsolved problem in colon and rectal surgery involves the treatment of locally invasive primary and recurrent rectal cancer. An approach is described that uses intracavitary iridium-192 sources in combination with a pelvic displacement prosthesis to augment external beam radiation doses to sites of residual disease identified at surgery. This approach should permit administration of tumoricidal doses of radiation to positive surgical margins minimizing radiation toxicity to the small bowel. The radiation source and all prosthetic materials are removed at the bedside within 2 weeks of surgery, ensuring accurate radiation dosimetry, minimizing infectious complications, and sparing the patient the need for full high-dose pelvic irradiation.

  12. Patient-Reported Outcomes as a Component of the Primary Endpoint in a Double-Blind, Placebo-Controlled Trial in Advanced Pancreatic Cancer

    PubMed Central

    Eckhardt, S. Gail; De Porre, Peter; Smith, David; Maurel, Joan; Steward, William P.; Bouche, Olivier; van de Velde, Helgi; Michiels, Bart; Bugat, Roland

    2010-01-01

    In this randomized, double-blind, placebo-controlled study comparing gemcitabine + tipifarnib (G + t) or gemcitabine + placebo (G + p) in patients with pancreatic cancer, the primary endpoint of time to deterioration (TTD) was based primarily on patient-reported outcomes. Deterioration was defined as death or worsening of disease-related symptoms, based on patient-reported outcomes of pain intensity and analgesic use in a daily diary, plus investigator-rated weekly performance status. Secondary endpoints included survival and safety. Two hundred and forty-four patients were treated for a total of 4780 weeks, during which the diary was completed daily. Overall, the completion of the diary was found to be feasible: patients completed approximately 95% of scheduled diary entries. Baseline characteristics were well balanced between the two treatment arms. The primary endpoint of TTD was not significantly different between the G + t arm (69 days) and the G + p arm (91 days, P = 0.40). Survival was not significantly different between the G + t arm (202 days) and the G + p arm (221 days, P = 0.66). The combination of G + t had an acceptable toxicity profile, with primarily neutropenia and thrombocytopenia. Methodologically, measurement of patient-reported outcomes is feasible and useful in assessing the effect of anti-cancer therapy in pancreatic cancer if comprehensive initial and ongoing training is provided to all people involved, including not only the patients but also the study personnel. PMID:18723314

  13. Surface modification of nano-silica on the ligament advanced reinforcement system for accelerated bone formation: primary human osteoblasts testing in vitro and animal testing in vivo.

    PubMed

    Li, Mengmeng; Wang, Shiwen; Jiang, Jia; Sun, Jiashu; Li, Yuzhuo; Huang, Deyong; Long, Yun-Ze; Zheng, Wenfu; Chen, Shiyi; Jiang, Xingyu

    2015-05-07

    The Ligament Advanced Reinforcement System (LARS) has been considered as a promising graft for ligament reconstruction. To improve its biocompatibility and effectiveness on new bone formation, we modified the surface of a polyethylene terephthalate (PET) ligament with nanoscale silica using atom transfer radical polymerization (ATRP) and silica polymerization. The modified ligament is tested by both in vitro and in vivo experiments. Human osteoblast testing in vitro exhibits an ∼21% higher value in cell viability for silica-modified grafts compared with original grafts. Animal testing in vivo shows that there is new formed bone in the case of a nanoscale silica-coated ligament. These results demonstrate that our approach for nanoscale silica surface modification on LARS could be potentially applied for ligament reconstruction.

  14. Surface modification of nano-silica on the ligament advanced reinforcement system for accelerated bone formation: primary human osteoblasts testing in vitro and animal testing in vivo

    NASA Astrophysics Data System (ADS)

    Li, Mengmeng; Wang, Shiwen; Jiang, Jia; Sun, Jiashu; Li, Yuzhuo; Huang, Deyong; Long, Yun-Ze; Zheng, Wenfu; Chen, Shiyi; Jiang, Xingyu

    2015-04-01

    The Ligament Advanced Reinforcement System (LARS) has been considered as a promising graft for ligament reconstruction. To improve its biocompatibility and effectiveness on new bone formation, we modified the surface of a polyethylene terephthalate (PET) ligament with nanoscale silica using atom transfer radical polymerization (ATRP) and silica polymerization. The modified ligament is tested by both in vitro and in vivo experiments. Human osteoblast testing in vitro exhibits an ~21% higher value in cell viability for silica-modified grafts compared with original grafts. Animal testing in vivo shows that there is new formed bone in the case of a nanoscale silica-coated ligament. These results demonstrate that our approach for nanoscale silica surface modification on LARS could be potentially applied for ligament reconstruction.The Ligament Advanced Reinforcement System (LARS) has been considered as a promising graft for ligament reconstruction. To improve its biocompatibility and effectiveness on new bone formation, we modified the surface of a polyethylene terephthalate (PET) ligament with nanoscale silica using atom transfer radical polymerization (ATRP) and silica polymerization. The modified ligament is tested by both in vitro and in vivo experiments. Human osteoblast testing in vitro exhibits an ~21% higher value in cell viability for silica-modified grafts compared with original grafts. Animal testing in vivo shows that there is new formed bone in the case of a nanoscale silica-coated ligament. These results demonstrate that our approach for nanoscale silica surface modification on LARS could be potentially applied for ligament reconstruction. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr01439e

  15. Interfractional Positional Variability of Fiducial Markers and Primary Tumors in Locally Advanced Non-Small-Cell Lung Cancer During Audiovisual Biofeedback Radiotherapy

    SciTech Connect

    Roman, Nicholas O.; Shepherd, Wes; Mukhopadhyay, Nitai; Hugo, Geoffrey D.; Weiss, Elisabeth

    2012-08-01

    Purpose: To evaluate implanted markers as a surrogate for tumor-based setup during image-guided lung cancer radiotherapy with audiovisual biofeedback. Methods and Materials: Seven patients with locally advanced non-small-cell lung cancer were implanted bronchoscopically with gold coils. Markers, tumor, and a reference bony structure (vertebra) were contoured for all 10 phases of the four-dimensional respiration-correlated fan-beam computed tomography and weekly four-dimensional cone-beam computed tomography. Results: The systematic/random interfractional marker-to-tumor centroid displacements were 2/3, 2/2, and 3/3 mm in the x (lateral), y (anterior-posterior), and z (superior-inferior) directions, respectively. The systematic/random interfractional marker-to-bone displacements were 2/3, 2/3, and 2/3 mm in the x, y, and z directions, respectively. The systematic/random tumor-to-bone displacements were 2/3, 2/4, and 4/4 mm in the x, y, and z directions, respectively. All displacements changed significantly over time (p < 0.0001). Conclusions: Although marker-based image guidance may decrease the risk for geometric miss compared with bony anatomy-based positioning, the observed displacements between markers and tumor centroids indicate the need for repeated soft tissue imaging, particularly in situations with large tumor volume change and large initial marker-to-tumor centroid distance.

  16. Amenorrhea - primary

    MedlinePlus

    ... of periods - primary Images Primary amenorrhea Normal uterine anatomy (cut section) Absence of menstruation (amenorrhea) References Bulun SE. The physiology and pathology of the female reproductive axis. In: ...

  17. SU-C-BRD-05: Implementation of Incident Learning in the Safety and Quality Management of Radiotherapy: The Primary Experience in a New Established Program with Advanced Techniques

    SciTech Connect

    Yang, R; Wang, J

    2014-06-15

    Purpose: To explore the implementation and effectiveness of incident learning for the safety and quality of radiotherapy in a new established radiotherapy program with advanced technology. Methods: Reference to the consensus recommendations by American Association of Physicist in Medicine, an incident learning system was specifically designed for reporting, investigating, and learning of individual radiotherapy incidents in a new established radiotherapy program, with 4D CBCT, Ultrasound guided radiotherapy, VMAT, gated treatment delivered on two new installed linacs. The incidents occurring in external beam radiotherapy from February, 2012 to January, 2014 were reported. Results: A total of 33 reports were analyzed, including 28 near misses and 5 incidents. Among them, 5 originated in imaging for planning, 25 in planning, 1 in plan transfer, 1 in commissioning and 1 in treatment delivery. Among them, three near misses originated in the safety barrier of the radiotherapy process. In terms of error type, 1 incident was classified as wrong patient, 7 near misses/incidents as wrong site, 6 as wrong laterality, 5 as wrong dose, 7 as wrong prescription, and 7 as suboptimal plan quality. 5 incidents were all classified as grade 1/2 of dosimetric severity, 1 as grade 0, and the other 4 as grade 1 of medical severity. For the causes/contributory factors, negligence, policy not followed, inadequate training, failure to develop an effective plan, and communication contributed to 19, 15, 12, 5 and 3 near misses/incidents, respectively. The average incident rate per 100 patients treated was 0.4; this rate fell to 0.28% in the second year from 0.56% in the first year. The rate of near miss fell to 1.24% from 2.22%. Conclusion: Effective incident learning can reduce the occurrence of near miss/incidents, enhance the culture of safety. Incident learning is an effective proactive method for improving the quality and safety of radiotherapy.

  18. Locoregionally Advanced Head and Neck Cancer Treated With Primary Radiotherapy: A Comparison of the Addition of Cetuximab or Chemotherapy and the Impact of Protocol Treatment

    SciTech Connect

    Caudell, Jimmy J.; Sawrie, Stephen M.; Spencer, Sharon A.; Desmond, Renee A.; Carroll, William R.; Peters, Glenn E.; Nabell, Lisle M.; Meredith, Ruby F.; Bonner, James A.

    2008-07-01

    Purpose: The addition of platinum-based chemotherapy (ChRT) or cetuximab (ExRT) to concurrent radiotherapy (RT) has resulted in improved survival in Phase III studies for locoregionally advanced head and neck cancer (LAHNC). However the optimal treatment regimen has not been defined. A retrospective study was performed to compare outcomes in patients who were treated definitively with ExRT or ChRT. Methods: Cetuximab with concurrent RT was used to treat 29 patients with LAHNC, all of whom had tumors of the oral cavity, oropharynx, or larynx. All patients were T2 to T4 and overall American Joint Committee on Cancer Stage III to IVB, with a Karnofsky Performance Status (KPS) score of 60 or greater. ChRT was used to treat 103 patients with similar characteristics. Patients were evaluated for locoregional control (LRC), distant metastasis-free survival (DMFS), disease-specific survival (DSS), and overall survival (OS). Median follow-up for patients alive at last contact was 83 months for those treated with ExRT and 53 months for those treated with ChRT. Cox proportional hazard models were used to assess independent prognostic factors. Results: The LRC, DMFS, and DSS were not significantly different, with 3-year rates of 70.7%, 92.4%, and 78.6% for ExRT and 74.7%, 86.6%, and 76.5% for ChRT, respectively. The OS was significantly different between the two groups (p = 0.02), with 3-year rates of 75.9% for ExRT and 61.3% for ChRT. OS was not significant when patients who were on protocol treatments of ExRT or ChRT were compared. Also, OS was not significant when multivariate analysis was used to control for potential confounding factors. Conclusion: In our single-institution retrospective review of patients treated with ExRT or ChRT, no significant differences were found in LRC, DMFS, DSS, or OS.

  19. Molecular analysis of myocilin and optineurin genes in Korean primary glaucoma patients

    PubMed Central

    Park, Joonhong; Kim, Myungshin; Park, Chan Kee; Chae, Hyojin; Lee, Seungok; Kim, Yonggoo; Jang, Woori; Chi, Hyun Young; Park, Hae-Young Lopilly; Park, Shin Hae

    2016-01-01

    To investigate the underlying genetic influences of primary glaucoma in Korea, molecular analysis was performed in 112 sporadic cases, and results compared with healthy controls. The myocilin (MYOC) and optineurin (OPTN) genes were directly sequenced in 112 unrelated patients, including 17 with primary open-angle glaucoma, 19 with juvenile open-angle glaucoma, and 76 with normal tension glaucoma. Healthy unrelated Korean individuals (n=100) were used as the non-selected population control. A total of three MYOC and four OPTN variants potentially associated with primary glaucoma were identified in 4 and 18 patients, respectively. A novel variant of MYOC, p.Leu255Pro, was predicted to be potentially pathogenic by in silico analysis. Another, p.Thr353Ile, has been previously reported. These two missense variants were detected in patients with a family history of glaucoma. Combined heterozygous variants p.[Thr123=;Ile288=] were identified in 2 of 112 (2%) patients but not in healthy controls. Among OPTN variants, a novel variant p.Arg271Cys was identified. Homozygous p.[Thr34=;Thr34=] (4/112, 4%), homozygous p.[Met98Lys;Met98Lys] (4/112, 4%), or combined heterozygous p.[Thr34=;Arg545Gln] (9/112, 8%) was significantly associated with the development of primary glaucoma [odds ratio (OR)=8.768, 95% confidence interval (CI)=1.972–38.988; relative risk=1.818, 95% CI=1.473–2.244; P=0.001]. The present study provides insight into the genetic or haplotype variants of MYOC and OPTN genes contributing to primary glaucoma. Haplotype variants identified in the present study may be regarded as potential contributing factors of primary glaucoma in Korea. Further studies, including those on additional genes, are required to elucidate the underlying pathogenic mechanism using a larger cohort to provide additional statistical power. PMID:27485216

  20. Chinese Herbal Formulation PHY906 and Sorafenib Tosylate in Treating Patients With Advanced Liver Cancer

    ClinicalTrials.gov

    2017-03-08

    Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Advanced Adult Hepatocellular Carcinoma; BCLC Stage B Adult Hepatocellular Carcinoma; BCLC Stage C Adult Hepatocellular Carcinoma

  1. Advancing Interprofessional Primary Health Care Services in Rural Settings for People with Chronic Low Back Disorders: Protocol of a Community-Based Randomized Controlled Trial

    PubMed Central

    Lovo Grona, Stacey; Milosavljevic, Stephan; Sari, Nazmi; Imeah, Biaka; O’Connell, Megan E

    2016-01-01

    September 2014 and data collection was completed in December 2015. Analysis is in progress and results are anticipated in 2017. Conclusions CLBD is a widespread public health problem, particularly in rural and remote areas, which requires new innovative approaches to deliver appropriate health care. The results of this project will inform the development of evidence-informed approaches and community-based implementation strategies to improve access to PT services in primary health care settings in other rural and remote underserved areas. Findings might also provide a framework for cost-effective and patient-centered models of service delivery for the management of other chronic conditions. ClinicalTrial ClinicalTrials.gov NCT02225535; https://clinicaltrials.gov/ct2/show/NCT02225535 (Archived by WebCite at http://www.webcitation.org/6lqLTCNF7) PMID:27829573

  2. Primary hyperoxaluria.

    PubMed

    Lorenzo, Víctor; Torres, Armando; Salido, Eduardo

    2014-05-21

    Primary hyperoxaluria (PH) occurs due to an autosomal recessive hereditary disorder of the metabolism of glyoxylate, which causes excessive oxalate production. The most frequent and serious disorder is due to enzyme deficit of alanine-glyoxylate aminotransferase (PH type I) specific to hepatic peroxisome. As oxalate is not metabolised in humans and is excreted through the kidneys, the kidney is the first organ affected, causing recurrent lithiasis, nephrocalcinosis and early renal failure. With advance of renal failure, particularly in patients on haemodialysis (HD), calcium oxalate is massively deposited in tissues, which is known as oxalosis. Diagnosis is based on family history, the presence of urolithiasis and/or nephrocalcinosis, hyperoxaluria, oxalate deposits in tissue forming granulomas, molecular analysis of DNA and enzyme analysis if applicable. High diagnostic suspicion is required; therefore, unfortunately, in many cases it is diagnosed after its recurrence following kidney transplantation. Conservative management of this disease (high liquid intake, pyridoxine and crystallisation inhibitors) needs to be adopted early in order to delay kidney damage. Treatment by dialysis is ineffective in treating excess oxalate. After the kidney transplant, we normally observe a rapid appearance of oxalate deposits in the graft and the results of this technique are discouraging, with very few exceptions. Pre-emptive liver transplantation, or simultaneous liver and kidney transplants when there is already irreversible damage to the kidney, is the treatment of choice to treat the underlying disease and suppress oxalate overproduction. Given its condition as a rare disease and its genetic and clinical heterogeneity, it is not possible to gain evidence through randomised clinical trials. As a result, the recommendations are established by groups of experts based on publications of renowned scientific rigour. In this regard, a group of European experts (OxalEurope) has

  3. Advancing the educational agenda.

    PubMed

    Baker, Cynthia

    2010-12-01

    This timely paper provides a thought-provoking analysis of current advanced practice nursing education in Canada. It comes at a critical juncture in the evolution of Canadian healthcare services and the redefinition of nursing roles. Increasingly, multiple sectors of society are calling for more nurses with advanced practice preparation and for a wider range of advanced practice nursing specialties. Advanced practice nurses (APNs) are being proposed as a solution to a financially overburdened national healthcare system, the increasing complexity of healthcare services, and a crisis in access to primary healthcare. Thus, governments seeking greater fiscal efficiency, medical specialists needing sophisticated collaborative support, and healthcare consumers see APNs as the way forward.

  4. Primary Hyperparathyroidism

    MedlinePlus

    ... What is PRIMARY HYPERPARATH YROIDIS M? The body’s parathyroid glands—four pea-sized glands in the neck—produce parathyroid hormone (PTH). Primary hyperparathyroidism (PHPT) is a condition ...

  5. Primary thrombocythemia

    MedlinePlus

    ... as myeloproliferative disorders. Others include: Chronic myelogenous leukemia Polycythemia vera Primary myelofibrosis This disorder is most common ... PA: Elsevier Saunders; 2013:chap 68. Tefferi A. Polycythemia vera, essential thrombocytoemia, and primary myelofibrosis. In: Goldman ...

  6. Primary Aldosteronism

    MedlinePlus

    ... Endocrinology Find an Endocrinologist Value of an Endocrinologist Learn About Clinical Trials Keep Your Body in Balance › Primary Aldosteronism Fact Sheet Primary Aldosteronism March 2012 Download PDFs English Espanol Editors Paul Stewart, MD, FRCP William Young, ...

  7. Trastuzumab Emtansine With or Without Pertuzumab Versus Trastuzumab Plus Taxane for Human Epidermal Growth Factor Receptor 2-Positive, Advanced Breast Cancer: Primary Results From the Phase III MARIANNE Study.

    PubMed

    Perez, Edith A; Barrios, Carlos; Eiermann, Wolfgang; Toi, Masakazu; Im, Young-Hyuck; Conte, Pierfranco; Martin, Miguel; Pienkowski, Tadeusz; Pivot, Xavier; Burris, Howard; Petersen, Jennifer A; Stanzel, Sven; Strasak, Alexander; Patre, Monika; Ellis, Paul

    2017-01-10

    Purpose Trastuzumab and pertuzumab are human epidermal growth factor receptor 2 (HER2) -targeted monoclonal antibodies, and trastuzumab emtansine (T-DM1) is an antibody-drug conjugate that combines the properties of trastuzumab with the cytotoxic activity of DM1. T-DM1 demonstrated encouraging efficacy and safety in a phase II study of patients with previously untreated HER2-positive metastatic breast cancer. Combination T-DM1 and pertuzumab showed synergistic activity in cell culture models and had an acceptable safety profile in a phase Ib and II study. Methods In the MARIANNE study, 1,095 patients with centrally assessed, HER2-positive, advanced breast cancer and no prior therapy for advanced disease were randomly assigned 1:1:1 to control (trastuzumab plus taxane), T-DM1 plus placebo, hereafter T-DM1, or T-DM1 plus pertuzumab at standard doses. Primary end point was progression-free survival (PFS), as assessed by independent review. Results T-DM1 and T-DM1 plus pertuzumab showed noninferior PFS compared with trastuzumab plus taxane (median PFS: 13.7 months with trastuzumab plus taxane, 14.1 months with T-DM1, and 15.2 months with T-DM1 plus pertuzumab). Neither experimental arm showed PFS superiority to trastuzumab plus taxane. Response rate was 67.9% in patients who were treated with trastuzumab plus taxane, 59.7% with T-DM1, and 64.2% with T-DM1 plus pertuzumab; median response duration was 12.5 months, 20.7 months, and 21.2 months, respectively. The incidence of grade ≥ 3 adverse events was numerically higher in the control arm (54.1%) versus the T-DM1 arm (45.4%) and T-DM1 plus pertuzumab arm (46.2%). Numerically fewer patients discontinued treatment because of adverse events in the T-DM1 arms, and health-related quality of life was maintained for longer in the T-DM1 arms. Conclusion T-DM1 showed noninferior, but not superior, efficacy and better tolerability than did taxane plus trastuzumab for first-line treatment of HER2-positive, advanced breast

  8. Glaucoma Genetics: Recent Advances and Future Directions.

    PubMed

    Aung, Tin; Khor, Chiea Chuen

    2016-01-01

    Once considered primarily a disease of aging caused by unknown environmental influences, the notion that heritable factors could significantly contribute to the pathogenesis of sporadic glaucoma has rapidly gained traction. In part, this is due to the rapid and definitive identification of genes with strong effects on familial, earlier onset forms of glaucoma. Although the endpoint of glaucoma is irreversible optic nerve damage accompanied by blindness, the initial inciting trigger could differ. To this end, well-powered genome-wide association studies have each been conducted for primary open-angle glaucoma, primary angle-closure glaucoma, along with exfoliation syndrome and glaucoma. Each of these studies has revealed sets of significantly associated genetic loci implicating biological pathways that do not overlap between the forms of glaucoma. Although substantial biological insight has been gained from their identification, much further work remains to definitively link the implicated genetic variants with glaucoma causation. It is also hoped that the genetic findings could point us to potential routes of therapy beyond that of intraocular pressure-lowering medications or surgery.

  9. Advancing Social Justice through Primary Prevention

    ERIC Educational Resources Information Center

    Mule, Christina; Lippus, Kathleen; Santora, Kimberly; Cicala, Gina; Smith, Bethany; Cataldo, Jessica; Li, Chieh

    2009-01-01

    A commitment to social justice is integral to being an effective school psychologist. While social justice is a term that is not easily defined, professionals in school psychology have characterized it as the idea that all students are entitled to be treated with fairness and respect. Though individual conceptions of social justice may vary, a…

  10. A phase II, single-arm study of the anti-α5β1 integrin antibody volociximab as monotherapy in patients with platinum-resistant advanced epithelial ovarian or primary peritoneal cancer

    PubMed Central

    Bell-McGuinn, Katherine M.; Matthews, Carolyn M.; Ho, Steffan N.; Barve, Minal; Gilbert, Lucy; Penson, Richard T.; Lengyel, Ernst; Palaparthy, Rameshraja; Gilder, Kye; Vassos, Artemios; McAuliffe, William; Weymer, Sara; Barton, Jeremy; Schilder, Russell J.

    2015-01-01

    Objective This phase II, multicenter, single-arm, two-stage study in platinum-resistant, advanced epithelial ovarian or primary peritoneal cancer evaluated the efficacy, safety, and tolerability of weekly single-agent volociximab. Pharmacokinetic/pharmacodynamic (PK/PD) studies were also performed. Methods Sixteen patients were enrolled in Stage 1. Volociximab was administered at 15 mg/kg IV qwk until progression of disease or drug intolerability. Tumor response was assessed every 8 weeks. Serum samples for PK or whole blood for the evaluation of circulating tumor cells, endothelial cells, and endothelial progenitor cells were obtained on Days 1, 8, 15, 29, and 50. Ascites from one patient was collected for volociximab concentration analysis. Archived tumor tissue was analyzed by immunohistochemistry (IHC) for α5 integrin expression. Results Safety data are available on all 16 patients; 14 were evaluable for efficacy. One patient had stable disease at 8 weeks. The remaining 13 progressed on treatment. Twelve patients (75%) experienced study-related adverse events (AEs); the most common (≥20%) were headache and fatigue. Three patients experienced possible study-related serious AEs (SAEs): reversible posterior leukoencephalopathy syndrome, pulmonary embolism, and hyponatremia. Peak serum concentrations of volociximab increased 2–3 fold from Day 1 to Day 50. Clinically relevant trough levels were achieved (>150 µg/mL). IHC analysis of archived tumor sections showed low-to-moderate expression of α5 integrin on all ovarian cancer tissue evaluated. Conclusion Despite insufficient clinical activity in this refractory patient population to continue the study, weekly volociximab was well tolerated, and the gained understanding of the mechanism of action of volociximab will inform future development efforts. PMID:21276608

  11. Prognostic factors for disease progression in advanced Hodgkin's disease: an analysis of patients aged under 60 years showing no progression in the first 6 months after starting primary chemotherapy.

    PubMed Central

    Lee, S. M.; Radford, J. A.; Ryder, W. D.; Collins, C. D.; Deakin, D. P.; Crowther, D.

    1997-01-01

    The aim of this study was to determine whether a very high-risk group based on presenting characteristics could be identified in patients with advanced Hodgkin's disease who may benefit from high-dose chemotherapy (HDCT). Between 1975 and 1992, 453 previously untreated patients aged under 60 years who did not progress in the first 6 months after the start of standard chemotherapy had their hospital notes reviewed. The outcomes analysed were early disease progression (in the 6- to 18-month window following the start of chemotherapy) and disease progression in the whole of the follow-up period. A Cox regression analysis was used to investigate the combined effects of a number of presenting characteristics on these outcomes. Despite the presence of factors with significant effects on the relative rate of progression, the absolute effects in a group identified as having the poorest prognosis were not especially poor. No group could be defined with a freedom from progression rate of less than 70% over 6-18 months, and the worst prognostic group, which included only 53 patients, had an overall freedom from progression rate of 57% at 5 years. Four other reported prognostic indices were evaluated using our data set, but none of the indices was more successful in identifying a very high-risk group. It has not been possible to define a sufficiently high-risk group of patients with Hodgkin's disease based on presenting characteristics for whom HDCT could be advised as part of primary treatment. The search for more discriminating prognostic factors identifying vulnerable patients with a high risk of relapse must continue before a role can be found for HDCT following conventional chemotherapy in patients without disease progression. PMID:9000607

  12. Primary Hyperparathyroidism

    MedlinePlus

    ... scans use a combination of x rays and computer technology to create three-dimensional (3-D) images. ... Research Resources Research at NIDDK Meetings & Events Technology Advancement & Transfer Health Information Diabetes Digestive Diseases Kidney Disease ...

  13. Primary Hyperparathyroidism

    MedlinePlus

    ... D blood test. This test is recommended because vitamin D deficiency is common in people with primary hyperparathyroidism. How ... bone density measurements every 1 to 2 years. Vitamin D deficiency should be corrected if present. Patients who are ...

  14. Advances in Fatigue and Fracture Mechanics Analyses for Aircraft Structures

    NASA Technical Reports Server (NTRS)

    Newman, J. C., Jr.

    1999-01-01

    This paper reviews some of the advances that have been made in stress analyses of cracked aircraft components, in the understanding of the fatigue and fatigue-crack growth process, and in the prediction of residual strength of complex aircraft structures with widespread fatigue damage. Finite-element analyses of cracked structures are now used to determine accurate stress-intensity factors for cracks at structural details. Observations of small-crack behavior at open and rivet-loaded holes and the development of small-crack theory has lead to the prediction of stress-life behavior for components with stress concentrations under aircraft spectrum loading. Fatigue-crack growth under simulated aircraft spectra can now be predicted with the crack-closure concept. Residual strength of cracked panels with severe out-of-plane deformations (buckling) in the presence of stiffeners and multiple-site damage can be predicted with advanced elastic-plastic finite-element analyses and the critical crack-tip-opening angle (CTOA) fracture criterion. These advances are helping to assure continued safety of aircraft structures.

  15. Achieving Target Pressures with Combined Surgery: Primary Patchless Ahmed Valve Combined with Phacoemulsification vs Primary Phacotrabeculectomy

    PubMed Central

    Sánchez-Noguera, Carmen C; Cárdenas-Gómez, Lorena; Castañeda-Diez, Rafael; Thomas, Ravi; Gil-Carrasco, Félix

    2015-01-01

    ABSTRACT Purpose: To evaluate the ability of phacoemulsification combined with either primary trabeculectomy (PT) or primary Ahmed glaucoma valve implantation (PAVI) to achieve target intraocular pressures (TIOP) in adults with primary open angle glaucoma. Materials and methods: Chart review of 214 adult patients operated between January 2002 and June 2008 with a minimum follow-up of 6 months. Group 1 comprised 181 eyes of 166 patients undergoing PT while group 2 included 50 eyes of 49 patients in combination with primary AVI. Target lOPs were pre-determined for each patient and success was defined as an IOP at or lower than target with or without medications. An IOP above target, loss of light perception or need for additional procedures to lower IOP were considered a failure. Results: Mean preoperative IOP was 17.2 mm Hg in group 1 and 17.3 in group 2. Mean postoperative IOPs were 10.2 and 9.2 on day 1, 12.2 and 11.6 at year 1, and 10.7 in both groups at year 5. Survival rates in groups 1 and 2 were 96.7 vs 96% at 6 months, 89 vs 96% at 12 months, 83.5 vs 96% at 24 months and 79.4 vs 89.1% at 36, 48 and 72 months. Transient bleb leaks were more frequent in group 1 (26 eyes, 14.4 vs 0%, p = 0.001) and transient choroidal detachments were more frequent in group 2 (7 eyes, 3.9 vs 6 eyes, 12%, p = 0.038). Conclusion: Midterm results for achieving target pressures using combined phacoemulsification with either PT or PAVI are comparable. The profile of complications is different for the two procedures. How to cite this article: Albis-Donado O, Sánchez-Noguera CC, Cárdenas-Gómez L, Castañeda-Diez R, Thomas R, Gil-Carrasco F. Achieving Target Pressures with Combined Surgery: Primary Patchless Ahmed Valve Combined with Phacoemulsification vs Primary Phacotrabeculectomy. J Curr Glaucoma Pract 2015;9(1):6-11. PMID:26997825

  16. Primary Ciliary Dyskinesia.

    PubMed

    Knowles, Michael R; Zariwala, Maimoona; Leigh, Margaret

    2016-09-01

    Primary ciliary dyskinesia (PCD) is a recessive genetically heterogeneous disorder of motile cilia with chronic otosinopulmonary disease and organ laterality defects in ∼50% of cases. The prevalence of PCD is difficult to determine. Recent diagnostic advances through measurement of nasal nitric oxide and genetic testing has allowed rigorous diagnoses and determination of a robust clinical phenotype, which includes neonatal respiratory distress, daily nasal congestion, and wet cough starting early in life, along with organ laterality defects. There is early onset of lung disease in PCD with abnormal airflow mechanics and radiographic abnormalities detected in infancy and early childhood.

  17. Primary to Post-Primary Transition for Students with Special Educational Needs from an Irish Context

    ERIC Educational Resources Information Center

    Foley, Tom; Foley, Shane; Curtin, Alicia

    2016-01-01

    This paper explores primary to post-primary transitions for students with Special Educational Needs (SEN) within mainstream schooling in an Irish context. A questionnaire was distributed to a cohort of sixth class students (n = 58) from four different primary schools in advance of their transfer and results were then compared with a similar cohort…

  18. Primary Science Education in China

    ERIC Educational Resources Information Center

    Pook, Gayle

    2013-01-01

    Consider the extent to which primary science teaching has evolved since it became a core subject in England with the introduction of the National Curriculum in 1988, and the pace at which theory-driven classroom practice has advanced. It is no wonder that, given the recent economic restructuring and boom in technological development in China,…

  19. Primary hyperparathyroidism.

    PubMed

    Govett, G; White, J

    1989-07-01

    Primary hyperparathyroidism is a pathological entity due to excessive secretion of parathormone from a single or multiple parathyroid glands. The biochemical hallmark of this disorder is an elevated serum calcium. The relationship of the parathyroid glands with the thymus gland in fetal development accounts for the occasional aberrant location of the parathyroids. By utilizing computed tomography or nuclear scanning or both preoperatively, the surgeon can isolate the hyperfunctioning adenoma and resect it, thus minimizing potential complications.

  20. Recent advances in pharmacotherapy of glaucoma

    PubMed Central

    Gupta, S. K.; Niranjan D., Galpalli; Agrawal, S. S.; Srivastava, Sushma; Saxena, Rohit

    2008-01-01

    Glaucoma is a slow progressive degeneration of the retinal ganglion cells (RGCs) and the optic nerve axons, leading to irreversible blindness if left undiagnosed and untreated. Although increased intraocular pressure is a major risk factor of glaucoma, other factors include increased glutamate levels, alterations in nitric oxide (NO) metabolism, vascular alterations and oxidative damage caused by reactive oxygen species. Glaucoma is the second leading cause of blindness globally, accounting for 12.3% of the total blindness. Glaucoma has been broadly classified as primary or secondary open-angle or angle-closure glaucoma. The primary goal in management of glaucoma is to prevent the risk factor, especially elevated intraocular pressure (IOP), using medications, laser therapy or conventional surgery. The first-line treatment of glaucoma usually begins with the use of a topical selective or nonselective blocker or a prostaglandin analog. Second-line drugs of choice include alpha-agonists and topical carbonic anhydrase inhibitors. Cholinergic agonists are considered third-line treatment options. When a single therapy is not sufficient to lower the IOP, a combination therapy is indicated. To enhance the patient compliance, drug delivery systems like electronic devices, ocular inserts, tansdermal and mechanical drug delivery systems have been developed. Use of viscoelastic agents in ophthalmic formulations, emulsions and soluble ophthalmic drug inserts (SODI) enhance patience compliance and ocular drug delivery in patients in long-term glaucoma therapy. For patients who do not respond to antiglaucoma medications, laser trabeculoplasty and incisional surgery are recommended. Several nutrients and botanicals hold promise for the treatment of glaucoma, but most studies are preliminary, and larger, controlled studies are required. Future directions for the development of a novel therapy glaucoma may target glutamate inhibition, NMDA receptor blockade, exogenously applied

  1. Motivating Inquiry in Statistics and Probability in the Primary Classroom

    ERIC Educational Resources Information Center

    Leavy, Aisling; Hourigan, Mairéad

    2015-01-01

    We describe how the use of a games environment combined with technology supports upper primary children in engaging with a concept traditionally considered too advanced for the primary classes: "The Law of Large Numbers."

  2. [Primary aldosteronism].

    PubMed

    Amar, Laurence

    2015-06-01

    Primary aldosteronism affects 6% of hypertensive patients. The diagnosis should be suspected in any patient with severe or resistant hypertension or hypertension associated with hypokalemia. The screening test consists on the assessment of the aldosterone to renin ratio. In case of an elevated ratio, the diagnosis of primary aldosteronism is confirmed by either elevated concentrations of basal plasma and/or urinary aldosterone or absence of suppression of aldosterone during dynamic test (including the saline infusion test). CT aims to ensure the absence of adrenal carcinoma and to study the morphology of the adrenals. The unilateral or bilateral type of aldosterone secretion is based on the realization of an adrenal venous sampling. When the hypersecretion is unilateral, the treatment consists of adrenalectomy leading to cure of hypertension in 42% of cases, improvement in 40% of cases. For patient with bilateral disease or who don't want to undergo surgery, treatment is based on spironolactone usually at doses of 25 or 50 mg in combination with other antihypertensives drugs such as diuretics or calcium channel blockers.

  3. Structural Change Can Be Detected in Advanced-Glaucoma Eyes

    PubMed Central

    Belghith, Akram; Medeiros, Felipe A.; Bowd, Christopher; Liebmann, Jeffrey M.; Girkin, Christopher A.; Weinreb, Robert N.; Zangwill, Linda M.

    2016-01-01

    Purpose To compare spectral-domain optical coherence tomography (SD-OCT) standard structural measures and a new three-dimensional (3D) volume optic nerve head (ONH) change detection method for detecting change over time in severely advanced-glaucoma (open-angle glaucoma [OAG]) patients. Methods Thirty-five eyes of 35 patients with very advanced glaucoma (defined as a visual field mean deviation < −21 dB) and 46 eyes of 30 healthy subjects to estimate aging changes were included. Circumpapillary retinal fiber layer thickness (cpRNFL), minimum rim width (MRW), and macular retinal ganglion cell–inner plexiform layer (GCIPL) thicknesses were measured using the San Diego Automated Layer Segmentation Algorithm (SALSA). Progression was defined as structural loss faster than 95th percentile of healthy eyes. Three-dimensional volume ONH change was estimated using the Bayesian-kernel detection scheme (BKDS), which does not require extensive retinal layer segmentation. Results The number of progressing glaucoma eyes identified was highest for 3D volume BKDS (13, 37%), followed by GCPIL (11, 31%), cpRNFL (4, 11%), and MRW (2, 6%). In advanced-OAG eyes, only the mean rate of GCIPL change reached statistical significance, −0.18 μm/y (P = 0.02); the mean rates of cpRNFL and MRW change were not statistically different from zero. In healthy eyes, the mean rates of cpRNFL, MRW, and GCIPL change were significantly different from zero. (all P < 0.001). Conclusions Ganglion cell–inner plexiform layer and 3D volume BKDS show promise for identifying change in severely advanced glaucoma. These results suggest that structural change can be detected in very advanced disease. Longer follow-up is needed to determine whether changes identified are false positives or true progression. PMID:27454660

  4. PET-CT in Determining the Radioembolization Dose Delivered to Patients With Liver Metastasis, Primary Liver Cancer, or Biliary Cancer

    ClinicalTrials.gov

    2017-01-24

    Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Metastatic Extrahepatic Bile Duct Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Stage D Adult Primary Liver Cancer (BCLC); Unspecified Adult Solid Tumor, Protocol Specific

  5. Primary gastric lymphoma

    PubMed Central

    Al-Akwaa, Ahmad M; Siddiqui, Neelam; Al-Mofleh, Ibrahim A

    2004-01-01

    AIM: The purpose of this review is to describe the various aspects of primary gastric lymphoma and the treatment options currently available. METHODS: After a systematic search of Pubmed, Medscape and MDconsult, we reviewed and retrieved literature regarding gastric lymphoma. RESULTS: Primary gastric lymphoma is rare however, the incidence of this malignancy is increasing. Chronic gastritis secondary to Helicobacter pylori (H pylori) infection has been considered a major predisposing factor for MALT lymphoma. Immune histochemical marker studies and molecular biology utilizing polymerase chain reaction have facilitated appropriate diagnosis and abolished the need for diagnostic surgical resection. Advances in imaging techniques including Magnetic Resonance Imaging (MRI) and Endoscopic Ultrasonography (EUS) have helped evaluation of tumor extension and invasion. The clinical course and prognosis of this disease is dependent on histopathological sub-type and stage at the time of diagnosis. Controversy remains regarding the best treatment for early stages of this disease. Chemotherapy, surgery and combination have been studied and shared almost comparable results with survival rate of 70%-90%. However, chemotherapy possesses the advantage of preserving gastric anatomy. Radiotherapy alone has been tried and showed good results. Stage IIIE, IVE disease treatment is solely by chemotherapy and surgical resection has been a remote consideration. CONCLUSION: We conclude that methods of diagnosis and staging of the primary gastric lymphoma have dramatically improved. The modalities of treatment are many and probably chemotherapy is superior because of high success rate, preservation of stomach and tolerable complications. PMID:14695759

  6. Advanced Science.

    ERIC Educational Resources Information Center

    Coles, Mike; Nelms, Rick

    1996-01-01

    Describes a study that explores the depth and breadth of scientific facts, principles, and procedures which are required in the Advanced General National Vocational Qualifications (GNVQ) science through comparison with GCE Advanced level. The final report takes account of the updated 1996 version of GNVQ science. (DDR)

  7. Advanced technology composite aircraft structures

    NASA Technical Reports Server (NTRS)

    Ilcewicz, Larry B.; Walker, Thomas H.

    1991-01-01

    Work performed during the 25th month on NAS1-18889, Advanced Technology Composite Aircraft Structures, is summarized. The main objective of this program is to develop an integrated technology and demonstrate a confidence level that permits the cost- and weight-effective use of advanced composite materials in primary structures of future aircraft with the emphasis on pressurized fuselages. The period from 1-31 May 1991 is covered.

  8. Recent Advances in Invasive Cardiology

    PubMed Central

    Garbe, George J.

    1987-01-01

    This paper describes recent advances in invasive cardiology that enable the primary-care physician to offer his/her patient a wider range of effective treatments. Major developments in the investigation and management of the acute coronary syndromes, unstable angina and myocardial infarction, have revolutionized the care of patients with these conditions. The primary-care physician must be aware of the treatment modalities, the lines of referral, and strategies for management available in his/her clinical setting to allow prompt application of these modalities. A sampling of exciting advances in other areas of invasive cardiology are also described. PMID:21263906

  9. Primary hyperparathyroidism

    PubMed Central

    Bilezikian, John P; Cusano, Natalie E.; Khan, Aliya A.; Liu, Jian-Min; Marcocci, Claudio; Bandeira, Francisco

    2017-01-01

    Primary hyperparathyroidism (PHPT) is a common disorder in which parathyroid hormone (PTH) is excessively secreted from one or more of the four parathyroid glands. A single benign parathyroid adenoma is the cause in most people. However, multiglandular disease is not rare and is typically seen in familial PHPT syndromes. The genetics of PHPT is usually monoclonal when a single gland is involved and polyclonal when multiglandular disease is present. The genes that have been implicated in PHPT include proto-oncogenes and tumour-suppressor genes. Hypercalcaemia is the biochemical hallmark of PHPT. Usually, the concentration of PTH is frankly increased but can remain within the normal range, which is abnormal in the setting of hypercalcaemia. Normocalcaemic PHPT, a variant in which the serum calcium level is persistently normal but PTH levels are increased in the absence of an obvious inciting stimulus, is now recognized. The clinical presentation of PHPT varies from asymptomatic disease (seen in countries where biochemical screening is routine) to classic symptomatic disease in which renal and/or skeletal complications are observed. Management guidelines have recently been revised to help the clinician to decide on the merits of a parathyroidectomy or a non-surgical course. This Primer covers these areas with particular attention to the epidemiology, clinical presentations, genetics, evaluation and guidelines for the management of PHPT. PMID:27194212

  10. The Coming Primary Care Revolution.

    PubMed

    Ellner, Andrew L; Phillips, Russell S

    2017-04-01

    The United States has the most expensive, technologically advanced, and sub-specialized healthcare system in the world, yet it has worse population health status than any other high-income country. Rising healthcare costs, high rates of waste, the continued trend towards chronic non-communicable disease, and the growth of new market entrants that compete with primary care services have set the stage for fundamental change in all of healthcare, driven by a revolution in primary care. We believe that the coming primary care revolution ought to be guided by the following design principles: 1) Payment must adequately support primary care and reward value, including non-visit-based care. 2) Relationships will serve as the bedrock of value in primary care, and will increasingly be fostered by teams, improved clinical operations, and technology, with patients and non-physicians assuming an ever-increasing role in most aspects of healthcare. 3) Generalist physicians will increasingly focus on high-acuity and high-complexity presentations, and primary care teams will increasingly manage conditions that specialists managed in the past. 4) Primary care will refocus on whole-person care, and address health behaviors as well as vision, hearing, dental, and social services. Design based on these principles should lead to higher-value healthcare, but will require new approaches to workforce training.

  11. Advanced Microsensors

    NASA Technical Reports Server (NTRS)

    1991-01-01

    This video looks at a spinoff application of the technology from advanced microsensors -- those that monitor and determine conditions of spacecraft like the Space Shuttle. The application featured is concerned with the monitoring of the health of premature babies.

  12. [Primary lipodystrophies].

    PubMed

    Capeau, J; Magré, J; Lascols, O; Caron, M; Béréziat, V; Vigouroux, C

    2007-02-01

    Primary lipodystrophies represent a heterogeneous group of very rare diseases with a prevalence of less than 1 case for 100.000, inherited or acquired, caracterized by a loss of body fat either generalized or localized (lipoatrophy). In some forms, lipoatrophy is associated with a selective hypertrophy of other fat depots. Clinical signs of insulin resistance are often present: acanthosis nigricans, signs of hyperandrogenism. All lipodystrophies are associated with dysmetabolic alterations with insulin resistance, altered glucose tolerance or diabetes and hypertriglyceridemia leading to a risk of acute pancreatitis. Chronic complications are those resulting from diabetes involving the retina, kidney and nerves, cardiovascular complications and steatotic liver lesions that could result in cirrhosis. Genetic forms of generalized lipodystrophy (or Berardinelli-Seip syndrome) result, in most cases, from recessive mutations in one of two genes: either BSCL2 coding seipin or BSCL1 coding AGPAT2, an acyl-transferase involved in triglyceride synthesis. Acquired generalized lipodystrophy (Lawrence syndrome) is of unknown origin but is sometimes associated with signs of autoimmunity. Partial lipodystrophies can be familial with dominant transmission. Heterozygous mutations have been identified in the LMNA gene encoding nuclear lamin A/C belonging to the nuclear lamina, or in PPARG encoding the adipogenic transcription factor PPARgamma. Some less typical lipodystrophies, associated with signs of premature aging, have been linked to mutations in LMNA or in the ZMPSTE24 gene encoding the protease responsible for the maturation of prelamin A into lamin A. Acquired partial lipodystrophy (Barraquer-Simons syndrome) is characterized by cephalothoracic fat loss. Its aetiology is unknown but mutations in LMNB2, encoding the lamina protein lamin B2, could represent susceptibility factors. Highly active antiretroviral treatments for HIV infection are currently the most frequent cause

  13. Influence of Pathological Nodal Status and Maximal Standardized Uptake Value of the Primary Tumor and Regional Lymph Nodes on Treatment Plans in Patients With Advanced Oral Cavity Squamous Cell Carcinoma

    SciTech Connect

    Liao, C.-T.; Wang, H.-M.; Chang, Joseph Tung-Chieh; Lin, C.-Y.; Ng, S.-H.; Huang, S.-F.; Chen, I.-H.; Hsueh Chuen; Lee, L.-Y.; Lin, C.-H.

    2010-06-01

    Purpose: A better understanding of the prognostic factors in oral cavity squamous cell carcinoma (OSCC) may optimize the therapeutic approach. In this study, we sought to investigate whether the combination of clinical information, pathologic results, and preoperative maximal standardized uptake value (SUVmax) at the primary tumor and regional lymph nodes might improve the prognostic stratification in this patient group. Methods and Materials: A total of 347 consecutive OSCC patients were investigated. All participants underwent fluorodeoxyglucose-positron emission tomography within 2 weeks before surgery and neck dissection. The duration of follow-up was at least 24 months in all surviving patients. The optimal cutoff values for SUVmax at the primary tumor (SUVtumor-max) and regional lymph nodes (SUVnodal-max) were selected according to the 5-year disease-free survival (DFS) rate. Independent prognosticators were identified by Cox regression analysis. Results: In multivariate analysis, a cutoff SUVtumor-max of 8.6, a cutoff SUVnodal-max of 5.7, and the presence of pathologic lymph node metastases were found to be significant prognosticators for the 5-year DFS. A scoring system using these three prognostic factors was formulated to define distinct prognostic groups. The 5-year rates for patients with a score between 0 and 3 were as follows: neck control, 94%, 86%, 77%, 59% (p < 0.0001); distant metastases, 1%, 7%, 22%, 47% (p < 0.0001); disease-specific survival, 93%, 85%, 61%, 36%, respectively (p < 0.0001). Conclusion: Based on the study findings, the combined evaluation of pathologic node status and SUVmax at the primary tumor and regional lymph nodes may improve prognostic stratification in OSCC patients.

  14. Exploring Best Practices in Advance Care Planning

    DTIC Science & Technology

    2016-05-11

    Background: The factors that influence completion of advance care planning for elderly adults in the primary care setting are poorly understood...System factors such as expansion of technological and medical options added to lists of tasks primary care providers are expected to complete in ever...to low rates of completion. We hypothesized that prioritized utilization of motivational interviewing during a visit specified to address advance care planning will enhance completion rates of appropriate planning.

  15. Advanced turbine systems program

    SciTech Connect

    Wilkes, C.; Mukavetz, D.W.; Knickerbocker, T.K.; Ali, S.A.

    1992-12-31

    In accordance with the goals of the DOE program, improvements in the gas turbine are the primary focus of Allison activity during Phase I. To this end Allison conducted a survey of potentially applicable gas turbine cycles and selected the advanced combined cycle as reference system. Extensive analysis of two versions of the advanced combined cycle was performed against the requirement for a 60% thermal efficiency (LHV) utility-sized, natural gas fired system. This analysis resulted in technology requirements for this system. Additional analysis determined emissions potential for the system, established a coal-fueled derivative system and a commercialization plan. This report deals with the technical requirements for a system that meets the thermal efficiency goal. Allison initially investigated four basic thermodynamic cycles: Humid air turbine, intercalate-recuperated systems, advanced combined cycle, chemically recuperated cycle. Our survey and cycle analysis indicated that au had the potential of reaching 60% thermal efficiency. We also concluded that engine hot section technology would be a critical technology regardless of which cycle was chosen. Based on this result Allison chose to concentrate on the advanced combined cycle. This cycle is well known and understood by the utility turbine user community and is therefore likely to be acceptable to users.

  16. Advanced turbine systems program

    SciTech Connect

    Wilkes, C.; Mukavetz, D.W.; Knickerbocker, T.K.; Ali, S.A.

    1992-01-01

    In accordance with the goals of the DOE program, improvements in the gas turbine are the primary focus of Allison activity during Phase I. To this end Allison conducted a survey of potentially applicable gas turbine cycles and selected the advanced combined cycle as reference system. Extensive analysis of two versions of the advanced combined cycle was performed against the requirement for a 60% thermal efficiency (LHV) utility-sized, natural gas fired system. This analysis resulted in technology requirements for this system. Additional analysis determined emissions potential for the system, established a coal-fueled derivative system and a commercialization plan. This report deals with the technical requirements for a system that meets the thermal efficiency goal. Allison initially investigated four basic thermodynamic cycles: Humid air turbine, intercalate-recuperated systems, advanced combined cycle, chemically recuperated cycle. Our survey and cycle analysis indicated that au had the potential of reaching 60% thermal efficiency. We also concluded that engine hot section technology would be a critical technology regardless of which cycle was chosen. Based on this result Allison chose to concentrate on the advanced combined cycle. This cycle is well known and understood by the utility turbine user community and is therefore likely to be acceptable to users.

  17. Advancing Reflectrometry

    DTIC Science & Technology

    2013-05-21

    transmissions, was first demonstrated using Global Navigation Satellite System ( GNSS ) reflections. Recently, reflectometry has been extended to digital... GNSS +R workshop provided an opportunity for engineers and Earth scientists to assess the state of the art, demonstrate new applications, and discuss...18 Eos, Vol. 94, No. 21, 21 May 2013 MEETING -.~ Advancing Reflectometry Workshop on Renectometry Using GNSS and Other Signals of Opportunity

  18. Technological Advancements

    ERIC Educational Resources Information Center

    Kennedy, Mike

    2010-01-01

    The influx of technology has brought significant improvements to school facilities. Many of those advancements can be found in classrooms, but when students head down the hall to use the washrooms, they are likely to find a host of technological innovations that have improved conditions in that part of the building. This article describes modern…

  19. Research Advances

    ERIC Educational Resources Information Center

    King, Angela G.

    2004-01-01

    Research advances, a new feature in Journal of Chemical Engineering that brings information about innovations in current areas of research to high school and college science faculty with an intent to provide educators with timely descriptions of latest progress in research that can be integrated into existing courses to update course content and…

  20. Advances in Fatigue and Fracture Mechanics Analyses for Metallic Aircraft Structures

    NASA Technical Reports Server (NTRS)

    Newman, J. C., Jr.

    2000-01-01

    This paper reviews some of the advances that have been made in stress analyses of cracked aircraft components, in the understanding of the fatigue and fatigue-crack growth process, and in the prediction of residual strength of complex aircraft structures with widespread fatigue damage. Finite-element analyses of cracked metallic structures are now used to determine accurate stress-intensity factors for cracks at structural details. Observations of small-crack behavior at open and rivet-loaded holes and the development of small-crack theory has lead to the prediction of stress-life behavior for components with stress concentrations under aircraft spectrum loading. Fatigue-crack growth under simulated aircraft spectra can now be predicted with the crack-closure concept. Residual strength of cracked panels with severe out-of-plane deformations (buckling) in the presence of stiffeners and multiple-site damage can be predicted with advanced elastic-plastic finite-element analyses and the critical crack-tip-opening angle (CTOA) fracture criterion. These advances are helping to assure continued safety of aircraft structures.

  1. [Long-term results of combined surgery for open-angle glaucoma].

    PubMed

    Baranov, I Ya; Shiryaev, I V; Mitrofanova, N V; Molodkina, N A; Balashevich, L I

    2017-01-01

    Цель — провести сравнительный анализ гипотензивного эффекта операций субсклерального удаления наружной стенки синуса с последующей лазерной трабекулопунктурой в микрофистулизирующем (1-й тип) и базовом (2-й тип) вариантах. Материал и методы. В основную группу вошли 60 пациентов (64 глаза), которым проведено лазерно-хирургическое лечение 1-го типа. Контрольную группу составили 105 пациентов (105 глаз), которым было выполнено вмешательство 2-го типа. Результаты. После хирургического этапа у 90,6% пациентов основной и 81,9% контрольной групп внутриглазное давление (ВГД) снизилось на 25% от исходного (p<0,05). После лазерной трабекулопунктуры ВГД снизилось до 15,6±0,4 мм рт.ст. в основной и до 17,4±0,3 мм рт.ст. в контрольной группах (p<0,05). Через 12 мес после комбинированного лазерно-хирургического лечения гипотензивный эффект без дополнительной гипотензивной терапии сохранился у 81,2% пациентов основной и 90,5% — контрольной группы (p<0,05). Заключение. Субсклеральное удаление наружной стенки синуса в микрофистулизирующем варианте с последующей лазерной трабекулопунктурой не менее эффективно по сравнению с базовым вариантом операции снижает ВГД у пациентов с ПОУГ.

  2. Development of Dorzolamide Loaded 6-O-Carboxymethyl Chitosan Nanoparticles for Open Angle Glaucoma

    PubMed Central

    Ahmed, Mohammed Hadi

    2013-01-01

    Chitosan (CS) is a biodegradable, biocompatible, and mucoadhesive natural polymer soluble in acidic pH only and can be irritating to the eye. Objective of the study was to synthesize water soluble 6-O-carboxymethyl (OCM-CS) derivative of CS, and to develop CS and OCM-CS nanoparticles (NPs) loaded with dorzolamide hydrochloride (DRZ). CS was reacted with monochloroacetic acid (MCA) for OCM-CS synthesis and was characterized by FT-IR, DSC, and 13C NMR. CS and OCM-CS NPs were prepared by ionic gelation method. Ocular irritation potential were evaluated and therapeutic efficacy was measured by reduction in intraocular pressure (IOP) in normotensive rabbits. Maximum yield was obtained when the ratio of water/isopropyl alcohol was 1/4 at 55°C. The FT-IR, DSC and 13C NMR confirmed the formation of an ether linkage between hydroxyl groups of CS and MCA. The particle size and zeta potential of optimised CSNPs was 250.3 ± 2.62 nm and +33.47 ± 0.723 mV, whereas those for OCM-CSNPs were 187.1 ± 2.72 nm and 30.87 ± 0.86 mV. The entrapment efficiency was significantly improved for OCM-CSNPs, compared to CSNPs. OCM-CSNPs had tailored drug release and improved bioavailability with reduction in pulse entry as compared to CSNPs. Hence, it can be concluded that DRZ loaded OCM-CSNPs would be better alternative option to available eye drops for glaucoma treatment. PMID:24222858

  3. Delta-9-tetrahydrocannabinol (THC) in the treatment of end-stage open-angle glaucoma.

    PubMed Central

    Flach, Allan J

    2002-01-01

    PURPOSE: Evidence exists that the administration of cannabinoid derivatives can lower intraocular pressure. Some patients with glaucoma believe they are being deprived of a potentially beneficial treatment. Therefore, the Research Advisory Panel of California instituted the Cannabis Therapeutic Research Program to permit compassionate access to cannabinoid derivatives. Data about the potential therapeutic usefulness and toxicity of these agents were collected. This study reviews the results of this program with the specific aim of providing further direction for these investigational efforts. METHODS: A survey of local ophthalmologists indicated an impressive interest in participating in and contributing patients with glaucoma unresponsive to treatment to this study. Appropriate patients were treated with either orally administered delta-9-tetrahydrocannabinol capsules or inhaled marijuana in addition to their existing therapeutic regimen. RESULTS: Although 20 ophthalmologists were approved as investigators, only nine patients were enrolled in the study. An initial decrease in intraocular pressure was observed in all patients, and the investigator's therapeutic goal was met in four of the nine patients. However, the decreases in intraocular pressure were not sustained, and all patients elected to discontinue treatment within 1 to 9 months for various reasons. CONCLUSIONS: This uncontrolled, unmasked, nonrandomized study does not permit definitive conclusions about the efficacy or toxicity of cannabinoids in the treatment of glaucoma. There is an impression that this treatment can lower intraocular pressure, but the development of tolerance and significant systemic toxicity appears to limit the usefulness of this potential treatment. Both patients and ophthalmologists greatly appreciated the opportunity to participate in this study. PMID:12545695

  4. Unilateral Open-Angle Glaucoma Associated with the Ipsilateral Nevus of Ota

    PubMed Central

    2013-01-01

    The nevus of Ota also known as “congenital melanosis bulbi” and “oculodermal melanocytosis” is a blue-gray hyperpigmentation that occurs on the face and eyes. The sclera is involved in two-thirds of cases (causing an increased risk of glaucoma). Women are nearly five times more likely to be affected than men. It is rare among Caucasian people. The nevus of Ota is congenital or acquired. Most cases of the nevus of Ota are unilateral (90%), although pigmentation is present bilaterally in 5%–10%. Ocular abnormalities included pigmentation of the sclera, cornea, retina, and optic disc and cavernous hemangiomas of the optic disc, elevated intraocular pressure, glaucoma, and ocular melanoma. We reported an appearance of unilateral glaucoma in a Caucasian female patient with the acquired, ipsilateral nevus of Ota. PMID:23781367

  5. SERI advanced wind turbine blades

    SciTech Connect

    Tangler, J.; Smith, B.; Jager, D.

    1992-02-01

    The primary goal of the Solar Energy Research Institute`s (SERI) advanced wind turbine blades is to convert the kinetic energy in the wind into mechanical energy in an inexpensive and efficient manner. To accomplish this goal, advanced wind turbine blades have been developed by SERI that utilize unique airfoil technology. Performance characteristics of the advanced blades were verified through atmospheric testing on fixed-pitch, stall-regulated horizontal-axis wind turbines (HAWTs). Of the various wind turbine configurations, the stall-regulated HAWT dominates the market because of its simplicity and low cost. Results of the atmospheric tests show that the SERI advanced blades produce 10% to 30% more energy than conventional blades. 6 refs.

  6. SERI advanced wind turbine blades

    SciTech Connect

    Tangler, J.; Smith, B.; Jager, D.

    1992-02-01

    The primary goal of the Solar Energy Research Institute's (SERI) advanced wind turbine blades is to convert the kinetic energy in the wind into mechanical energy in an inexpensive and efficient manner. To accomplish this goal, advanced wind turbine blades have been developed by SERI that utilize unique airfoil technology. Performance characteristics of the advanced blades were verified through atmospheric testing on fixed-pitch, stall-regulated horizontal-axis wind turbines (HAWTs). Of the various wind turbine configurations, the stall-regulated HAWT dominates the market because of its simplicity and low cost. Results of the atmospheric tests show that the SERI advanced blades produce 10% to 30% more energy than conventional blades. 6 refs.

  7. Primary Progressive Aphasia

    MedlinePlus

    Primary progressive aphasia Overview By Mayo Clinic Staff Primary progressive aphasia (uh-FAY-zhuh) is a rare nervous system (neurological) syndrome ... your ability to communicate. People with primary progressive aphasia can have trouble expressing their thoughts and understanding ...

  8. Advanced Combustion

    SciTech Connect

    Holcomb, Gordon R.

    2013-03-11

    The activity reported in this presentation is to provide the mechanical and physical property information needed to allow rational design, development and/or choice of alloys, manufacturing approaches, and environmental exposure and component life models to enable oxy-fuel combustion boilers to operate at Ultra-Supercritical (up to 650{degrees}C & between 22-30 MPa) and/or Advanced Ultra-Supercritical conditions (760{degrees}C & 35 MPa).

  9. Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME.

    PubMed

    Godoy, Patricio; Hewitt, Nicola J; Albrecht, Ute; Andersen, Melvin E; Ansari, Nariman; Bhattacharya, Sudin; Bode, Johannes Georg; Bolleyn, Jennifer; Borner, Christoph; Böttger, Jan; Braeuning, Albert; Budinsky, Robert A; Burkhardt, Britta; Cameron, Neil R; Camussi, Giovanni; Cho, Chong-Su; Choi, Yun-Jaie; Craig Rowlands, J; Dahmen, Uta; Damm, Georg; Dirsch, Olaf; Donato, María Teresa; Dong, Jian; Dooley, Steven; Drasdo, Dirk; Eakins, Rowena; Ferreira, Karine Sá; Fonsato, Valentina; Fraczek, Joanna; Gebhardt, Rolf; Gibson, Andrew; Glanemann, Matthias; Goldring, Chris E P; Gómez-Lechón, María José; Groothuis, Geny M M; Gustavsson, Lena; Guyot, Christelle; Hallifax, David; Hammad, Seddik; Hayward, Adam; Häussinger, Dieter; Hellerbrand, Claus; Hewitt, Philip; Hoehme, Stefan; Holzhütter, Hermann-Georg; Houston, J Brian; Hrach, Jens; Ito, Kiyomi; Jaeschke, Hartmut; Keitel, Verena; Kelm, Jens M; Kevin Park, B; Kordes, Claus; Kullak-Ublick, Gerd A; LeCluyse, Edward L; Lu, Peng; Luebke-Wheeler, Jennifer; Lutz, Anna; Maltman, Daniel J; Matz-Soja, Madlen; McMullen, Patrick; Merfort, Irmgard; Messner, Simon; Meyer, Christoph; Mwinyi, Jessica; Naisbitt, Dean J; Nussler, Andreas K; Olinga, Peter; Pampaloni, Francesco; Pi, Jingbo; Pluta, Linda; Przyborski, Stefan A; Ramachandran, Anup; Rogiers, Vera; Rowe, Cliff; Schelcher, Celine; Schmich, Kathrin; Schwarz, Michael; Singh, Bijay; Stelzer, Ernst H K; Stieger, Bruno; Stöber, Regina; Sugiyama, Yuichi; Tetta, Ciro; Thasler, Wolfgang E; Vanhaecke, Tamara; Vinken, Mathieu; Weiss, Thomas S; Widera, Agata; Woods, Courtney G; Xu, Jinghai James; Yarborough, Kathy M; Hengstler, Jan G

    2013-08-01

    This review encompasses the most important advances in liver functions and hepatotoxicity and analyzes which mechanisms can be studied in vitro. In a complex architecture of nested, zonated lobules, the liver consists of approximately 80 % hepatocytes and 20 % non-parenchymal cells, the latter being involved in a secondary phase that may dramatically aggravate the initial damage. Hepatotoxicity, as well as hepatic metabolism, is controlled by a set of nuclear receptors (including PXR, CAR, HNF-4α, FXR, LXR, SHP, VDR and PPAR) and signaling pathways. When isolating liver cells, some pathways are activated, e.g., the RAS/MEK/ERK pathway, whereas others are silenced (e.g. HNF-4α), resulting in up- and downregulation of hundreds of genes. An understanding of these changes is crucial for a correct interpretation of in vitro data. The possibilities and limitations of the most useful liver in vitro systems are summarized, including three-dimensional culture techniques, co-cultures with non-parenchymal cells, hepatospheres, precision cut liver slices and the isolated perfused liver. Also discussed is how closely hepatoma, stem cell and iPS cell-derived hepatocyte-like-cells resemble real hepatocytes. Finally, a summary is given of the state of the art of liver in vitro and mathematical modeling systems that are currently used in the pharmaceutical industry with an emphasis on drug metabolism, prediction of clearance, drug interaction, transporter studies and hepatotoxicity. One key message is that despite our enthusiasm for in vitro systems, we must never lose sight of the in vivo situation. Although hepatocytes have been isolated for decades, the hunt for relevant alternative systems has only just begun.

  10. A polymorphism in the CYP1B1 promoter is functionally associated with primary congenital glaucoma.

    PubMed

    Chakrabarti, Subhabrata; Ghanekar, Yashoda; Kaur, Kiranpreet; Kaur, Inderjeet; Mandal, Anil K; Rao, Kollu N; Parikh, Rajul S; Thomas, Ravi; Majumder, Partha P

    2010-10-15

    Primary congenital glaucoma (PCG) is a childhood autosomal-recessive disorder caused by developmental defects in the trabecular meshwork and anterior chamber angle. These defects cause raised intraocular pressure (IOP) that damages the optic nerve and if left untreated, results in irreversible blindness. Mutations in CYP1B1 gene at the GLC3A locus (2p21) are associated with PCG. However, there has been very limited exploration of its promoter region. We resequenced the CYP1B1 promoter in a large cohort (n = 835) that included patients with PCG (n = 301), other primary glaucomas (primary open-angle glaucoma: n = 115 and primary angle closure glaucoma: n = 100) and unaffected controls (n = 319). We functionally characterized one associated variant by luciferase reporter assay using the trabecular meshwork (TM3) cell line. We found evidence of strong (P = 6.01 × 10(-4)) association of rs2567206 (T2805C) SNP in PCG and not in other primary glaucomas. Luciferase assay indicated a ∼90% reduction in CYP1B1 promoter activity in the risk-allele (C) compared to the other allele (T). The association of the risk allele was stronger in cases harboring homozygous CYP1B1 mutations (P = 3.42 × 10(-12)). The risk haplotype 'C-C-G' in the promoter had a strong non-random association to the previously characterized risk haplotype 'C-G-G-T-A' in the coding region. The independent effect of genotype at the promoter T2805C locus (P = 0.001), and the interaction effect of genotypes at the promoter and coding region mutations loci (P = 0.001) were significant for the presenting IOP of the worst affected eye. This is the first study that unequivocally shows the functional involvement of a CYP1B1 promoter variant in PCG.

  11. Neutropenia in primary immunodeficiency

    PubMed Central

    Sokolic, Robert

    2016-01-01

    Purpose of review Neutropenia is a feature of several primary immunodeficiency diseases (PIDDs). Because of the diverse pathophysiologies of the PIDDs and the rarity of each disorder, data are often lacking, leading to the necessity of empiric treatment. Recent developments in the understanding of neutropenia in several of the PIDDs make a review of the data timely. Recent findings The category of severe congenital neutropenia continues to expand. Mutations in G6PC3 have been identified as the cause of neutropenia in a minority of previously molecularly undefined cases. Recent advances have broadened our understanding of the pathophysiology and the clinical expression of this disorder. A possible function of the C16orf57 gene has been hypothesized that may explain the clinical overlap between Clerucuzio-type poikiloderma with neutropenia and other marrow diseases. Plerixafor has been shown to be a potentially useful treatment in the warts, hypogammaglobulinemia, infection, and myelokathexis syndrome. Investigations of patients with adenosine deaminase deficient severe combined immunodeficiency have identified neutropenia, and particularly susceptibility to myelotoxins, as a feature of this disorder. Granulocyte-colony stimulating factor is the treatment of choice for neutropenia in PIDD, whereas hematopoietic cell transplantation is the only curative option. Summary The number of PIDDs associated with neutropenia has increased, as has our understanding of the range of phenotypes. Additional data and hypotheses have been generated helping to explain the diversity of presentations of neutropenia in PIDDs. PMID:23196894

  12. [Metachronous four primary malignancies in gastro-intestinal tract].

    PubMed

    Bae, Jung Min; Kim, Se Won; Kim, Sang Woon; Song, Sun Kyo

    2009-06-01

    Multiple primary malignancy was reported firstly by Billroth in 1889. Recently, multiple primary malignancies are considered to increase due to improved survival rate of cancer patients, advanced diagnostic tools, and increased use of chemotherapy and radiotherapy. In Korea, several cases of triple primary malignancies were reported. However, four primary malignancies in gastro-intestinal tract was rarely reported. Recently, we experienced a 70 year-old male who was diagnosed with metachronous four primary malignancies in rectum, ascending colon, stomach, and ampulla of Vater. We report this rare case of metachronous four primary malignancies with a review of literature.

  13. Advanced LIGO

    NASA Astrophysics Data System (ADS)

    LIGO Scientific Collaboration; Aasi, J.; Abbott, B. P.; Abbott, R.; Abbott, T.; Abernathy, M. R.; Ackley, K.; Adams, C.; Adams, T.; Addesso, P.; Adhikari, R. X.; Adya, V.; Affeldt, C.; Aggarwal, N.; Aguiar, O. D.; Ain, A.; Ajith, P.; Alemic, A.; Allen, B.; Amariutei, D.; Anderson, S. B.; Anderson, W. G.; Arai, K.; Araya, M. C.; Arceneaux, C.; Areeda, J. S.; Ashton, G.; Ast, S.; Aston, S. M.; Aufmuth, P.; Aulbert, C.; Aylott, B. E.; Babak, S.; Baker, P. T.; Ballmer, S. W.; Barayoga, J. C.; Barbet, M.; Barclay, S.; Barish, B. C.; Barker, D.; Barr, B.; Barsotti, L.; Bartlett, J.; Barton, M. A.; Bartos, I.; Bassiri, R.; Batch, J. C.; Baune, C.; Behnke, B.; Bell, A. S.; Bell, C.; Benacquista, M.; Bergman, J.; Bergmann, G.; Berry, C. P. L.; Betzwieser, J.; Bhagwat, S.; Bhandare, R.; Bilenko, I. A.; Billingsley, G.; Birch, J.; Biscans, S.; Biwer, C.; Blackburn, J. K.; Blackburn, L.; Blair, C. D.; Blair, D.; Bock, O.; Bodiya, T. P.; Bojtos, P.; Bond, C.; Bork, R.; Born, M.; Bose, Sukanta; Brady, P. R.; Braginsky, V. B.; Brau, J. E.; Bridges, D. O.; Brinkmann, M.; Brooks, A. F.; Brown, D. A.; Brown, D. D.; Brown, N. M.; Buchman, S.; Buikema, A.; Buonanno, A.; Cadonati, L.; Calderón Bustillo, J.; Camp, J. B.; Cannon, K. C.; Cao, J.; Capano, C. D.; Caride, S.; Caudill, S.; Cavaglià, M.; Cepeda, C.; Chakraborty, R.; Chalermsongsak, T.; Chamberlin, S. J.; Chao, S.; Charlton, P.; Chen, Y.; Cho, H. S.; Cho, M.; Chow, J. H.; Christensen, N.; Chu, Q.; Chung, S.; Ciani, G.; Clara, F.; Clark, J. A.; Collette, C.; Cominsky, L.; Constancio, M., Jr.; Cook, D.; Corbitt, T. R.; Cornish, N.; Corsi, A.; Costa, C. A.; Coughlin, M. W.; Countryman, S.; Couvares, P.; Coward, D. M.; Cowart, M. J.; Coyne, D. C.; Coyne, R.; Craig, K.; Creighton, J. D. E.; Creighton, T. D.; Cripe, J.; Crowder, S. G.; Cumming, A.; Cunningham, L.; Cutler, C.; Dahl, K.; Dal Canton, T.; Damjanic, M.; Danilishin, S. L.; Danzmann, K.; Dartez, L.; Dave, I.; Daveloza, H.; Davies, G. S.; Daw, E. J.; DeBra, D.; Del Pozzo, W.; Denker, T.; Dent, T.; Dergachev, V.; DeRosa, R. T.; DeSalvo, R.; Dhurandhar, S.; D´ıaz, M.; Di Palma, I.; Dojcinoski, G.; Dominguez, E.; Donovan, F.; Dooley, K. L.; Doravari, S.; Douglas, R.; Downes, T. P.; Driggers, J. C.; Du, Z.; Dwyer, S.; Eberle, T.; Edo, T.; Edwards, M.; Edwards, M.; Effler, A.; Eggenstein, H.-B.; Ehrens, P.; Eichholz, J.; Eikenberry, S. S.; Essick, R.; Etzel, T.; Evans, M.; Evans, T.; Factourovich, M.; Fairhurst, S.; Fan, X.; Fang, Q.; Farr, B.; Farr, W. M.; Favata, M.; Fays, M.; Fehrmann, H.; Fejer, M. M.; Feldbaum, D.; Ferreira, E. C.; Fisher, R. P.; Frei, Z.; Freise, A.; Frey, R.; Fricke, T. T.; Fritschel, P.; Frolov, V. V.; Fuentes-Tapia, S.; Fulda, P.; Fyffe, M.; Gair, J. R.; Gaonkar, S.; Gehrels, N.; Gergely, L. Á.; Giaime, J. A.; Giardina, K. D.; Gleason, J.; Goetz, E.; Goetz, R.; Gondan, L.; González, G.; Gordon, N.; Gorodetsky, M. L.; Gossan, S.; Goßler, S.; Gräf, C.; Graff, P. B.; Grant, A.; Gras, S.; Gray, C.; Greenhalgh, R. J. S.; Gretarsson, A. M.; Grote, H.; Grunewald, S.; Guido, C. J.; Guo, X.; Gushwa, K.; Gustafson, E. K.; Gustafson, R.; Hacker, J.; Hall, E. D.; Hammond, G.; Hanke, M.; Hanks, J.; Hanna, C.; Hannam, M. D.; Hanson, J.; Hardwick, T.; Harry, G. M.; Harry, I. W.; Hart, M.; Hartman, M. T.; Haster, C.-J.; Haughian, K.; Hee, S.; Heintze, M.; Heinzel, G.; Hendry, M.; Heng, I. S.; Heptonstall, A. W.; Heurs, M.; Hewitson, M.; Hild, S.; Hoak, D.; Hodge, K. A.; Hollitt, S. E.; Holt, K.; Hopkins, P.; Hosken, D. J.; Hough, J.; Houston, E.; Howell, E. J.; Hu, Y. M.; Huerta, E.; Hughey, B.; Husa, S.; Huttner, S. H.; Huynh, M.; Huynh-Dinh, T.; Idrisy, A.; Indik, N.; Ingram, D. R.; Inta, R.; Islas, G.; Isler, J. C.; Isogai, T.; Iyer, B. R.; Izumi, K.; Jacobson, M.; Jang, H.; Jawahar, S.; Ji, Y.; Jiménez-Forteza, F.; Johnson, W. W.; Jones, D. I.; Jones, R.; Ju, L.; Haris, K.; Kalogera, V.; Kandhasamy, S.; Kang, G.; Kanner, J. B.; Katsavounidis, E.; Katzman, W.; Kaufer, H.; Kaufer, S.; Kaur, T.; Kawabe, K.; Kawazoe, F.; Keiser, G. M.; Keitel, D.; Kelley, D. B.; Kells, W.; Keppel, D. G.; Key, J. S.; Khalaidovski, A.; Khalili, F. Y.; Khazanov, E. A.; Kim, C.; Kim, K.; Kim, N. G.; Kim, N.; Kim, Y.-M.; King, E. J.; King, P. J.; Kinzel, D. L.; Kissel, J. S.; Klimenko, S.; Kline, J.; Koehlenbeck, S.; Kokeyama, K.; Kondrashov, V.; Korobko, M.; Korth, W. Z.; Kozak, D. B.; Kringel, V.; Krishnan, B.; Krueger, C.; Kuehn, G.; Kumar, A.; Kumar, P.; Kuo, L.; Landry, M.; Lantz, B.; Larson, S.; Lasky, P. D.; Lazzarini, A.; Lazzaro, C.; Le, J.; Leaci, P.; Leavey, S.; Lebigot, E. O.; Lee, C. H.; Lee, H. K.; Lee, H. M.; Leong, J. R.; Levin, Y.; Levine, B.; Lewis, J.; Li, T. G. F.; Libbrecht, K.; Libson, A.; Lin, A. C.; Littenberg, T. B.; Lockerbie, N. A.; Lockett, V.; Logue, J.; Lombardi, A. L.; Lormand, M.; Lough, J.; Lubinski, M. J.; Lück, H.; Lundgren, A. P.; Lynch, R.; Ma, Y.; Macarthur, J.; MacDonald, T.; Machenschalk, B.; MacInnis, M.; Macleod, D. M.; Magaña-Sandoval, F.; Magee, R.; Mageswaran, M.; Maglione, C.; Mailand, K.; Mandel, I.; Mandic, V.; Mangano, V.; Mansell, G. L.; Márka, S.; Márka, Z.; Markosyan, A.; Maros, E.; Martin, I. W.; Martin, R. M.; Martynov, D.; Marx, J. N.; Mason, K.; Massinger, T. J.; Matichard, F.; Matone, L.; Mavalvala, N.; Mazumder, N.; Mazzolo, G.; McCarthy, R.; McClelland, D. E.; McCormick, S.; McGuire, S. C.; McIntyre, G.; McIver, J.; McLin, K.; McWilliams, S.; Meadors, G. D.; Meinders, M.; Melatos, A.; Mendell, G.; Mercer, R. A.; Meshkov, S.; Messenger, C.; Meyers, P. M.; Miao, H.; Middleton, H.; Mikhailov, E. E.; Miller, A.; Miller, J.; Millhouse, M.; Ming, J.; Mirshekari, S.; Mishra, C.; Mitra, S.; Mitrofanov, V. P.; Mitselmakher, G.; Mittleman, R.; Moe, B.; Mohanty, S. D.; Mohapatra, S. R. P.; Moore, B.; Moraru, D.; Moreno, G.; Morriss, S. R.; Mossavi, K.; Mow-Lowry, C. M.; Mueller, C. L.; Mueller, G.; Mukherjee, S.; Mullavey, A.; Munch, J.; Murphy, D.; Murray, P. G.; Mytidis, A.; Nash, T.; Nayak, R. K.; Necula, V.; Nedkova, K.; Newton, G.; Nguyen, T.; Nielsen, A. B.; Nissanke, S.; Nitz, A. H.; Nolting, D.; Normandin, M. E. N.; Nuttall, L. K.; Ochsner, E.; O'Dell, J.; Oelker, E.; Ogin, G. H.; Oh, J. J.; Oh, S. H.; Ohme, F.; Oppermann, P.; Oram, R.; O'Reilly, B.; Ortega, W.; O'Shaughnessy, R.; Osthelder, C.; Ott, C. D.; Ottaway, D. J.; Ottens, R. S.; Overmier, H.; Owen, B. J.; Padilla, C.; Pai, A.; Pai, S.; Palashov, O.; Pal-Singh, A.; Pan, H.; Pankow, C.; Pannarale, F.; Pant, B. C.; Papa, M. A.; Paris, H.; Patrick, Z.; Pedraza, M.; Pekowsky, L.; Pele, A.; Penn, S.; Perreca, A.; Phelps, M.; Pierro, V.; Pinto, I. M.; Pitkin, M.; Poeld, J.; Post, A.; Poteomkin, A.; Powell, J.; Prasad, J.; Predoi, V.; Premachandra, S.; Prestegard, T.; Price, L. R.; Principe, M.; Privitera, S.; Prix, R.; Prokhorov, L.; Puncken, O.; Pürrer, M.; Qin, J.; Quetschke, V.; Quintero, E.; Quiroga, G.; Quitzow-James, R.; Raab, F. J.; Rabeling, D. S.; Radkins, H.; Raffai, P.; Raja, S.; Rajalakshmi, G.; Rakhmanov, M.; Ramirez, K.; Raymond, V.; Reed, C. M.; Reid, S.; Reitze, D. H.; Reula, O.; Riles, K.; Robertson, N. A.; Robie, R.; Rollins, J. G.; Roma, V.; Romano, J. D.; Romanov, G.; Romie, J. H.; Rowan, S.; Rüdiger, A.; Ryan, K.; Sachdev, S.; Sadecki, T.; Sadeghian, L.; Saleem, M.; Salemi, F.; Sammut, L.; Sandberg, V.; Sanders, J. R.; Sannibale, V.; Santiago-Prieto, I.; Sathyaprakash, B. S.; Saulson, P. R.; Savage, R.; Sawadsky, A.; Scheuer, J.; Schilling, R.; Schmidt, P.; Schnabel, R.; Schofield, R. M. S.; Schreiber, E.; Schuette, D.; Schutz, B. F.; Scott, J.; Scott, S. M.; Sellers, D.; Sengupta, A. S.; Sergeev, A.; Serna, G.; Sevigny, A.; Shaddock, D. A.; Shahriar, M. S.; Shaltev, M.; Shao, Z.; Shapiro, B.; Shawhan, P.; Shoemaker, D. H.; Sidery, T. L.; Siemens, X.; Sigg, D.; Silva, A. D.; Simakov, D.; Singer, A.; Singer, L.; Singh, R.; Sintes, A. M.; Slagmolen, B. J. J.; Smith, J. R.; Smith, M. R.; Smith, R. J. E.; Smith-Lefebvre, N. D.; Son, E. J.; Sorazu, B.; Souradeep, T.; Staley, A.; Stebbins, J.; Steinke, M.; Steinlechner, J.; Steinlechner, S.; Steinmeyer, D.; Stephens, B. C.; Steplewski, S.; Stevenson, S.; Stone, R.; Strain, K. A.; Strigin, S.; Sturani, R.; Stuver, A. L.; Summerscales, T. Z.; Sutton, P. J.; Szczepanczyk, M.; Szeifert, G.; Talukder, D.; Tanner, D. B.; Tápai, M.; Tarabrin, S. P.; Taracchini, A.; Taylor, R.; Tellez, G.; Theeg, T.; Thirugnanasambandam, M. P.; Thomas, M.; Thomas, P.; Thorne, K. A.; Thorne, K. S.; Thrane, E.; Tiwari, V.; Tomlinson, C.; Torres, C. V.; Torrie, C. I.; Traylor, G.; Tse, M.; Tshilumba, D.; Ugolini, D.; Unnikrishnan, C. S.; Urban, A. L.; Usman, S. A.; Vahlbruch, H.; Vajente, G.; Valdes, G.; Vallisneri, M.; van Veggel, A. A.; Vass, S.; Vaulin, R.; Vecchio, A.; Veitch, J.; Veitch, P. J.; Venkateswara, K.; Vincent-Finley, R.; Vitale, S.; Vo, T.; Vorvick, C.; Vousden, W. D.; Vyatchanin, S. P.; Wade, A. R.; Wade, L.; Wade, M.; Walker, M.; Wallace, L.; Walsh, S.; Wang, H.; Wang, M.; Wang, X.; Ward, R. L.; Warner, J.; Was, M.; Weaver, B.; Weinert, M.; Weinstein, A. J.; Weiss, R.; Welborn, T.; Wen, L.; Wessels, P.; Westphal, T.; Wette, K.; Whelan, J. T.; Whitcomb, S. E.; White, D. J.; Whiting, B. F.; Wilkinson, C.; Williams, L.; Williams, R.; Williamson, A. R.; Willis, J. L.; Willke, B.; Wimmer, M.; Winkler, W.; Wipf, C. C.; Wittel, H.; Woan, G.; Worden, J.; Xie, S.; Yablon, J.; Yakushin, I.; Yam, W.; Yamamoto, H.; Yancey, C. C.; Yang, Q.; Zanolin, M.; Zhang, Fan; Zhang, L.; Zhang, M.; Zhang, Y.; Zhao, C.; Zhou, M.; Zhu, X. J.; Zucker, M. E.; Zuraw, S.; Zweizig, J.

    2015-04-01

    The Advanced LIGO gravitational wave detectors are second-generation instruments designed and built for the two LIGO observatories in Hanford, WA and Livingston, LA, USA. The two instruments are identical in design, and are specialized versions of a Michelson interferometer with 4 km long arms. As in Initial LIGO, Fabry-Perot cavities are used in the arms to increase the interaction time with a gravitational wave, and power recycling is used to increase the effective laser power. Signal recycling has been added in Advanced LIGO to improve the frequency response. In the most sensitive frequency region around 100 Hz, the design strain sensitivity is a factor of 10 better than Initial LIGO. In addition, the low frequency end of the sensitivity band is moved from 40 Hz down to 10 Hz. All interferometer components have been replaced with improved technologies to achieve this sensitivity gain. Much better seismic isolation and test mass suspensions are responsible for the gains at lower frequencies. Higher laser power, larger test masses and improved mirror coatings lead to the improved sensitivity at mid and high frequencies. Data collecting runs with these new instruments are planned to begin in mid-2015.

  14. Advanced Pacemaker

    NASA Technical Reports Server (NTRS)

    1990-01-01

    Synchrony, developed by St. Jude Medical's Cardiac Rhythm Management Division (formerly known as Pacesetter Systems, Inc.) is an advanced state-of-the-art implantable pacemaker that closely matches the natural rhythm of the heart. The companion element of the Synchrony Pacemaker System is the Programmer Analyzer APS-II which allows a doctor to reprogram and fine tune the pacemaker to each user's special requirements without surgery. The two-way communications capability that allows the physician to instruct and query the pacemaker is accomplished by bidirectional telemetry. APS-II features 28 pacing functions and thousands of programming combinations to accommodate diverse lifestyles. Microprocessor unit also records and stores pertinent patient data up to a year.

  15. Improving Advanced High School Physics

    NASA Astrophysics Data System (ADS)

    Spital, Robin David

    2003-04-01

    A National Research Council study committee recently commissioned a "Physics Panel" to evaluate and make recommendations for improving advanced physics education in American high schools [1]. The Physics Panel recommends the creation of a nationally standardized Newtonian Mechanics Unit that would form the foundation of all advanced physics programs. In a one-year program, the Panel recommends that advanced physics students study at most one other major area of physics, so that sufficient time is available to develop the deep conceptual understanding that is the primary goal of advanced study. The Panel emphasizes that final assessments must be improved to focus on depth of understanding, rather than technical problem-solving skill. The Physics Panel strongly endorses the inclusion of meaningful real-world experiences in advanced physics programs, but believes that traditional "cook-book" laboratory exercises are not worth the enormous amount of time and effort spent on them. The Physics Panel believes that the talent and preparation of teachers are the most important ingredients in effective physics instruction; it therefore calls for a concerted effort by all parts of the physics community to remedy the desperate shortage of highly qualified teachers. [1] Jerry P. Gollub and Robin Spital, "Advanced Physics in the High Schools", Physics Today, May 2002.

  16. Advanced subsystems development

    NASA Technical Reports Server (NTRS)

    Livingston, F. R.

    1978-01-01

    The concept design for a small (less than 10 MWe) solar thermal electric generating plant was completed using projected 1985 technology. The systems requirements were defined and specified. The components, including an engineering prototype for one 15 kWe module of the generating plant, were conceptually designed. Significant features of the small solar thermal power plant were identified as the following: (1) 15 kWe Stirling-cycle engine/alternator with constant power output; (2) 10 meter point-focusing paraboloidal concentrator with cantilevered cellular glass reflecting panels; (3) primary heat pipe with 800 C output solar cavity receiver; (4) secondary heat pipe with molten salt thermal energy storage unit; (5) electric energy transport system; and (6) advanced battery energy storage capability.

  17. Advanced dive monitoring system.

    PubMed

    Sternberger, W I; Goemmer, S A

    1999-01-01

    The US Navy supports deep diving operations with a variety of mixed-gas life support systems. A systems engineering study was conducted for the Naval Experimental Dive Unit (Panama City, FL) to develop a concept design for an advanced dive monitoring system. The monitoring system is intended primarily to enhance diver safety and secondarily to support diving medicine research. Distinct monitoring categories of diver physiology, life support system, and environment are integrated in the monitoring system. A system concept is proposed that accommodates real-time and quantitative measurements, noninvasive physiological monitoring, and a flexible and expandable implementation architecture. Human factors and ergonomic design considerations have been emphasized to assure that there is no impact on the diver's primary mission. The Navy has accepted the resultant system requirements and the basic design concept. A number of monitoring components have been implemented and successfully support deep diving operations.

  18. Advanced Stage, Increased Lactate Dehydrogenase, and Primary Site, but Not Adolescent Age (≥ 15 Years), Are Associated With an Increased Risk of Treatment Failure in Children and Adolescents With Mature B-Cell Non-Hodgkin's Lymphoma: Results of the FAB LMB 96 Study

    PubMed Central

    Cairo, Mitchell S.; Sposto, Richard; Gerrard, Mary; Auperin, Anne; Goldman, Stanton C.; Harrison, Lauren; Pinkerton, Ross; Raphael, Martine; McCarthy, Keith; Perkins, Sherrie L.; Patte, Catherine

    2012-01-01

    Purpose Adolescents (age 15 to 21 years) compared with younger children with mature B-cell non-Hodgkin's lymphoma (NHL) have been historically considered to have an inferior prognosis. We therefore analyzed the impact of age and other diagnostic factors on the risk of treatment failure in children and adolescents treated on the French-American-British Mature B-Cell Lymphoma 96 (FAB LMB 96) trial. Patients and Methods Patients were divided by risk: group A (limited), group B (intermediate), and group C (advanced), as previously described. Prognostic factors analyzed for event-free survival (EFS) included age (< 15 v ≥ 15 years), stage (I/II v III/IV), primary site, lactate dehydrogenase (LDH), bone marrow/CNS (BM/CNS) involvement, and histology (diffuse large B-cell lymphoma v mediastinal B-cell lymphoma v Burkitt lymphoma or Burkitt-like lymphoma). Results The 3-year EFS for the whole cohort was 88% ± 1%. Age was not associated as a risk factor for increased treatment failure in either univariate analysis (P = .15) or multivariate analysis (P = .58). Increased LDH (≥ 2 × upper limit of normal [ULN] v < 2 × ULN), primary site, and BM-positive/CNS-positive disease were all independent risk factors associated with a significant increase in treatment failure rate (relative risk, 2.0; P < .001, P < .012, and P < .001, respectively). Conclusion LDH level at diagnosis, mediastinal disease, and combined BM-positive/CNS-positive involvement are independent risk factors in children with mature B-cell NHL. Future studies should be developed to identify specific therapeutic strategies (immunotherapy) to overcome these risk factors and to identify the biologic basis associated with these prognostic factors in children with mature B-cell NHL. PMID:22215753

  19. Primary orbital melanoma without ocular involvement in a Balinese cat

    PubMed Central

    2006-01-01

    Abstract A 6.5-year-old spayed female Balinese cat was diagnosed with a large and locally invasive primary orbital melanoma, without ocular involvement or detectable metastatic disease. Advanced imaging and immunohistochemical studies helped in obtaining the diagnosis. Because of advanced unresectable disease and ensuing poor quality of life, the cat was euthanized. PMID:16604977

  20. Brain tumor - primary - adults

    MedlinePlus

    ... Vestibular schwannoma (acoustic neuroma) - adults; Meningioma - adults; Cancer - brain tumor (adults) ... Primary brain tumors include any tumor that starts in the brain. Primary brain tumors can start from brain cells, ...

  1. Primary renal carcinoid tumor.

    PubMed

    Kanodia, K V; Vanikar, A V; Patel, R D; Suthar, K S; Kute, V B; Modi, P R; Trivedi, H L

    2013-09-01

    Primary renal carcinoid tumor is extremely rare and, therefore, its pathogenesis and prognosis is not well known. We report a primary renal carcinoid in a 26-year-old man treated by radical nephrectomy.

  2. Advanced stellarators

    NASA Astrophysics Data System (ADS)

    Schlüter, Arnulf

    1983-03-01

    Toroidal confinement of a plasma by an external magnetic field is not compatible with axisymmetry, in contrast to confinement by the pinch effect of induced electric currents as in a tokomak or by the reversed field pinch configuration. The existence of magnetic surfaces throughout the region in which grad p ≠ 0 is therefore not guaranteed in such configurations, though it is necessary for MHD-equilibrium when the lines of force possess a finite twist (or "rotational transform"). These twisted equilibria are called stellarators. The other type of external confinement requires all lines of force to be closed upon themselves and p to be function of the well defined quantity Q = φ d l/ B only. The resulting "bumpy" tori are sometimes also referred to as being M + S like. By discussing specific examples it is shown that stellarator configurations exist which retain as much as possible the properties of M + S like configurations, combine these with the magnetic well, and with an approximation to the isodynamic requirement of D. Palumbo. These so-called Advanced Stellarators shown an improvement in predicted particle confinement and beta-limit compared to the classical stellarators. They can also be viewed as forming a system of linked stabilized mirrors of small mirror ratio. These fields can be produced by modular coils. A prototype of such a configuration is being designed by the stellarator division of IPP under the name of Wendelstein VII-AS. Expected physical data and technical details of W VII-AS are given.

  3. Primary enzyme quantitation

    DOEpatents

    Saunders, G.C.

    1982-03-04

    The disclosure relates to the quantitation of a primary enzyme concentration by utilizing a substrate for the primary enzyme labeled with a second enzyme which is an indicator enzyme. Enzyme catalysis of the substrate occurs and results in release of the indicator enzyme in an amount directly proportional to the amount of primary enzyme present. By quantifying the free indicator enzyme one determines the amount of primary enzyme present.

  4. Investigating Primary Source Literacy

    ERIC Educational Resources Information Center

    Archer, Joanne; Hanlon, Ann M.; Levine, Jennie A.

    2009-01-01

    Primary source research requires students to acquire specialized research skills. This paper presents results from a user study testing the effectiveness of a Web guide designed to convey the concepts behind "primary source literacy". The study also evaluated students' strengths and weaknesses when conducting primary source research. (Contains 3…

  5. Primary Care's Dim Prognosis

    ERIC Educational Resources Information Center

    Alper, Philip R.

    2010-01-01

    Given the chorus of approval for primary care emanating from every party to the health reform debate, one might suppose that the future for primary physicians is bright. Yet this is far from certain. And when one looks to history and recognizes that primary care medicine has failed virtually every conceivable market test in recent years, its…

  6. Primary brain tumours in adults.

    PubMed

    Ricard, Damien; Idbaih, Ahmed; Ducray, François; Lahutte, Marion; Hoang-Xuan, Khê; Delattre, Jean-Yves

    2012-05-26

    Important advances have been made in the understanding and management of adult gliomas and primary CNS lymphomas--the two most common primary brain tumours. Progress in imaging has led to a better analysis of the nature and grade of these tumours. Findings from large phase 3 studies have yielded some standard treatments for gliomas, and have confirmed the prognostic value of specific molecular alterations. High-throughput methods that enable genome-wide analysis of tumours have improved the knowledge of tumour biology, which should lead to a better classification of gliomas and pave the way for so-called targeted therapy trials. Primary CNS lymphomas are a group of rare non-Hodgkin lymphomas. High-dose methotrexate-based regimens increase survival, but the standards of care and the place of whole-brain radiotherapy remain unclear, and are likely to depend on the age of the patient. The focus now is on the development of new polychemotherapy regimens to reduce or defer whole-brain radiotherapy and its delayed complications.

  7. Working with Advanced Primary School Students in Physics

    NASA Astrophysics Data System (ADS)

    Jankovic, Ljiljana; Cucic, Dragoljub

    2010-01-01

    Working with students who have special needs is the type of work that requires special engagement and skills of those who perform it. Working with gifted children requires outstanding knowledge of a teacher and above all the teachers should be very well informed on the subject they teach, Physics in our case. This work also requires great pedagogical and psychological skills so that these talented students would be approached in a suitable way. In this paper we will present to you our methods of teaching Physics to these talented children (13 years old), in the Regional Center for Talents "Mihajlo Pupin" in Pancevo.

  8. Advanced Mirror System Demonstrator (AMSD) Risk Management

    NASA Technical Reports Server (NTRS)

    Byberg, Alicia; Russell, J. Kevin; Kaukler, Donna; Burdine, Robert V. (Technical Monitor)

    2002-01-01

    This paper will report risk issues associated with designing, manufacturing, and testing the Advanced Mirror System Demonstrator (AMSD). The Advanced Mirror System Demonstrator (AMSD) will be developed as a lightweight primary mirror system that can be produced at a low cost and with a short manufacturing schedule. This technology will add to the knowledge base for selection for the Next Generation Space Telescope (NGST), Space Based Laser (SBL), Research Laboratory mission (AFRL), and other government agency programs.

  9. Immunoglobulin Replacement Therapy for Primary Immunodeficiency.

    PubMed

    Sriaroon, Panida; Ballow, Mark

    2015-11-01

    Immunoglobulin replacement therapy has been standard treatment in patients with primary immunodeficiency diseases for the past 3 decades. The goal of therapy is to reduce serious bacterial infections in individuals with antibody function defects. Approximately one-third of patients receiving intravenous immunoglobulin treatment experience adverse reactions. Recent advances in manufacturing processes have resulted in products that are safer and better tolerated. Self-infusion by the subcutaneous route has become popular and resulted in better quality of life. This review summarizes the use of immunoglobulin therapy in primary immunodeficiency diseases including its properties, dosing, adverse effects, and different routes of administration.

  10. Composites technology for transport primary structure

    NASA Technical Reports Server (NTRS)

    Chen, Victor; Hawley, Arthur; Klotzsche, Max; Markus, Alan; Palmer, Ray

    1991-01-01

    The ACT contract activity being performed by the McDonnell Douglas Corporation is divided into two separate activities: one effort by Douglas Aircraft in Long Beach, California with a focus on Transport Primary Wing and Fuselage Structure, and the other effort by McDonnell Aircraft in St. Louis, Missouri with a focus on Advanced Combat Aircraft Center Wing-Fuselage Structure. This presentation is on the Douglas Aircraft Transport Structure portion of the ACT program called ICAPS - Innovative Composite Aircraft Primary Structure.

  11. SCIENCE BRIEF: ADVANCED CONCEPTS

    EPA Science Inventory

    Research on advanced concepts will evaluate and demonstrate the application of innovative infrastructure designs, management procedures and operational approaches. Advanced concepts go beyond simple asset management. The infusion of these advanced concepts into established wastew...

  12. Isotope separation and advanced manufacturing technology

    NASA Astrophysics Data System (ADS)

    Carpenter, J.; Kan, T.

    This is the fourth issue of a semiannual report for the Isotope Separation and Advanced Materials Manufacturing (ISAM) Technology Program at Lawrence Livermore National Laboratory. Primary objectives include: (1) the Uranium Atomic Vapor Laser Isotope Separation (UAVLIS) process, which is being developed and prepared for deployment as an advanced uranium enrichment capability; (2) Advanced manufacturing technologies, which include industrial laser and E-beam material processing and new manufacturing technologies for uranium, plutonium, and other strategically important materials in support of DOE and other national applications. This report features progress in the ISAM Program from October 1993 through March 1994.

  13. [Chemoradiotherapy for locally advanced cervical cancer].

    PubMed

    Bazaeva, I Ia; Gorbunova, V A; Kravets, O A; Khokhlova, S V; Limareva, S V; Panov, V O; Strel'tsova, O N; Tarachkova, E V

    2014-01-01

    Cervical cancer takes second place in morbidity and third place in mortality from gynecological cancer. Advanced stages among newly diagnosed cases is still large. The "gold standard" of treatment for locally advanced cervical cancer is chemoradiotherapy with cisplatin that results in a lower risk of death. Improvement of radiotherapy methods allowed to bring optimal dose to the primary tumor with the inclusion of regional metastasis areas with less risk of damage to surrounding healthy tissue and organs. The search for alternative combinations of cytostatics, modes of drug administration, adjuvant chemotherapy after chemoradiotherapy showed an increase in survival of patients with locally advanced cervical cancer.

  14. Primary Intraosseous Meningioma.

    PubMed

    Chen, Thomas C

    2016-04-01

    Primary intraosseous meningiomas are a subtype of primary extradural meningiomas. They represent approximately two-thirds of extradural meningiomas and fewer than 2% of meningiomas overall. These tumors originate within the bones of the skull and can have a clinical presentation and radiographic differential diagnosis different from those for intradural meningiomas. Primary intraosseous meningiomas are classified based on location and histopathologic characteristics. Treatment is primarily surgical resection with wide margins if possible. Sparse literature exists regarding the use of adjuvant therapies. The literature regarding primary intraosseous meningiomas consists primarily of clinical case reports and case series. This literature is reviewed and summarized in this article.

  15. Management Of Primary Sclerosing Cholangitis

    PubMed Central

    Sandhu, Bimaljit S.

    2006-01-01

    Management of primary sclerosing cholangitis (PSC) can be divided into endoscopic, medical, and surgical treatments. Whereas endoscopic therapy is primarily used to manage dominant strictures, medical treatment is directed both at modifying course of the disease and at symptomatic relief. Ursodeoxycholic acid is the most promising disease-modifying agent. Corticosteroids and other immunosuppressive agents do not have a proven role. Cholestyramine and rifampicin improve pruritis but response to these agents cannot be reliably predicted. Opioid antagonists are useful in refractory pruritis. All patients with advanced PSC should be offered bone mineral-density measurement and, if needed, treatment for osteoporosis. These approaches are not mutually exclusive and are often used concurrently or in sequence depending on the clinical situation. Liver transplantation is the only therapy that improves survival. In this review, we discuss the various management options for PSC.

  16. Accrediting advanced practice: who will benefit?

    PubMed

    2017-02-27

    Last month I attended the 2017 RCN advanced nurse practitioner (ANP) conference in London. The title of the conference referred to 'moving the agenda forward' and there were many examples of ANPs pioneering developments in emergency care, primary care, acute medicine, mental health and other services.

  17. EMR Curriculum Guide: Primary.

    ERIC Educational Resources Information Center

    Ruschmeier, Veronica M., Ed.; Rockwell, Linda, Ed.

    Presented is a curriculum guide for educable mentally retarded children in primary and intermediate grades which specifies behavioral and interim objectives in the areas of basic verbal and arithmetic skills, vocational competencies, social competencies, and physical skills. Objectives such as the following are identified at the primary level:…

  18. Using Primary Source Documents.

    ERIC Educational Resources Information Center

    Mintz, Steven

    2003-01-01

    Explores the use of primary sources when teaching about U.S. slavery. Includes primary sources from the Gilder Lehrman Documents Collection (New York Historical Society) to teach about the role of slaves in the Revolutionary War, such as a proclamation from Lord Dunmore offering freedom to slaves who joined his army. (CMK)

  19. Medics in Primary School

    ERIC Educational Resources Information Center

    Press, Colin

    2003-01-01

    Some time ago a flyer on "Medics in Primary School" came the author's way. It described a programme for making placements in primary schools available to medical students. The benefits of the program to medical students and participating schools were highlighted, including opportunities to develop communication skills and demystify…

  20. Transforming Primary Mathematics

    ERIC Educational Resources Information Center

    Askew, Mike

    2011-01-01

    What is good mathematics teaching? What is mathematics teaching good for? Who is mathematics teaching for? These are just some of the questions addressed in "Transforming Primary Mathematics", a highly timely new resource for teachers which accessibly sets out the key theories and latest research in primary maths today. Under-pinned by findings…

  1. Increasing the Capacity of Primary Care Through Enabling Technology.

    PubMed

    Young, Heather M; Nesbitt, Thomas S

    2017-02-27

    Primary care is the foundation of effective and high-quality health care. The role of primary care clinicians has expanded to encompass coordination of care across multiple providers and management of more patients with complex conditions. Enabling technology has the potential to expand the capacity for primary care clinicians to provide integrated, accessible care that channels expertise to the patient and brings specialty consultations into the primary care clinic. Furthermore, technology offers opportunities to engage patients in advancing their health through improved communication and enhanced self-management of chronic conditions. This paper describes enabling technologies in four domains (the body, the home, the community, and the primary care clinic) that can support the critical role primary care clinicians play in the health care system. It also identifies challenges to incorporating these technologies into primary care clinics, care processes, and workflow.

  2. Advanced Hypervelocity Aerophysics Facility Workshop

    NASA Technical Reports Server (NTRS)

    Witcofski, Robert D. (Compiler); Scallion, William I. (Compiler)

    1989-01-01

    The primary objective of the workshop was to obtain a critical assessment of a concept for a large, advanced hypervelocity ballistic range test facility powered by an electromagnetic launcher, which was proposed by the Langley Research Center. It was concluded that the subject large-scale facility was feasible and would provide the required ground-based capability for performing tests at entry flight conditions (velocity and density) on large, complex, instrumented models. It was also concluded that advances in remote measurement techniques and particularly onboard model instrumentation, light-weight model construction techniques, and model electromagnetic launcher (EML) systems must be made before any commitment for the construction of such a facility can be made.

  3. [The primary healthcare centres].

    PubMed

    Brambilla, Antonio; Maciocco, Gavino

    2014-04-01

    The central attributes of primary care are: first contact (accessibility), longitudinality (person- focused preventive and curative care overtime), patient-oriented comprehensiveness and coordination (including navigation towards secondary and tertiary care). Besides taking care of the needs of the individuals, primary health care teams are also looking at the community, especially when addressing social determinants of health. The rationale for the benefits for primary care for health has been found in: 1) greater access to needed services; 2) better quality of care; 3) a greater focus on prevention; 4) early management of health problems; 5) organizing and delivering high quality care for chronic non-communicable diseases. This paper describes the role of primary healthcare centres in strengthening community primary services and in reducing health inequalities. Furthemore, the experiences of Regional Health Services from Tuscany and Emilia-Romagna are discussed, with a brief overview of the literature.

  4. Primary Intraocular Lymphoma

    PubMed Central

    Faia, Lisa J.; Chan, Chi-Chao

    2009-01-01

    Primary intraocular lymphoma, recently suggested to be renamed primary retinal lymphoma, is a subset of primary central nervous system lymphoma and is usually an aggressive diffuse large B-cell lymphoma. Between 56% and 85% of patients who initially present with primary intraocular lymphoma alone will develop cerebral lesions. Patients typically complain of decreased vision and floaters, most likely secondary to the chronic vitritis and subretinal lesions. The diagnosis of primary intraocular lymphoma can be difficult to make and requires tissue for diagnosis. The atypical lymphoid cells are large and display a high nuclear to cytoplasmic ratio, prominent nucleoli, and basophilic cytoplasm. Flow cytometry, immunohistochemistry, cytokine analysis, and gene rearrangements also aid in the diagnosis. Local and systemic treatments, such as chemotherapy and radiation, are employed, although the relapse rate remains high. PMID:19653715

  5. ADVANCED TURBINE SYSTEMS PROGRAM

    SciTech Connect

    Gregory Gaul

    2004-04-21

    Natural gas combustion turbines are rapidly becoming the primary technology of choice for generating electricity. At least half of the new generating capacity added in the US over the next twenty years will be combustion turbine systems. The Department of Energy has cosponsored with Siemens Westinghouse, a program to maintain the technology lead in gas turbine systems. The very ambitious eight year program was designed to demonstrate a highly efficient and commercially acceptable power plant, with the ability to fire a wide range of fuels. The main goal of the Advanced Turbine Systems (ATS) Program was to develop ultra-high efficiency, environmentally superior and cost effective competitive gas turbine systems for base load application in utility, independent power producer and industrial markets. Performance targets were focused on natural gas as a fuel and included: System efficiency that exceeds 60% (lower heating value basis); Less than 10 ppmv NO{sub x} emissions without the use of post combustion controls; Busbar electricity that are less than 10% of state of the art systems; Reliability-Availability-Maintainability (RAM) equivalent to current systems; Water consumption minimized to levels consistent with cost and efficiency goals; and Commercial systems by the year 2000. In a parallel effort, the program was to focus on adapting the ATS engine to coal-derived or biomass fuels. In Phase 1 of the ATS Program, preliminary investigators on different gas turbine cycles demonstrated that net plant LHV based efficiency greater than 60% was achievable. In Phase 2 the more promising cycles were evaluated in greater detail and the closed-loop steam-cooled combined cycle was selected for development because it offered the best solution with least risk for achieving the ATS Program goals for plant efficiency, emissions, cost of electricity and RAM. Phase 2 also involved conceptual ATS engine and plant design and technology developments in aerodynamics, sealing

  6. Advanced gray rod control assembly

    DOEpatents

    Drudy, Keith J; Carlson, William R; Conner, Michael E; Goldenfield, Mark; Hone, Michael J; Long, Jr., Carroll J; Parkinson, Jerod; Pomirleanu, Radu O

    2013-09-17

    An advanced gray rod control assembly (GRCA) for a nuclear reactor. The GRCA provides controlled insertion of gray rod assemblies into the reactor, thereby controlling the rate of power produced by the reactor and providing reactivity control at full power. Each gray rod assembly includes an elongated tubular member, a primary neutron-absorber disposed within the tubular member said neutron-absorber comprising an absorber material, preferably tungsten, having a 2200 m/s neutron absorption microscopic capture cross-section of from 10 to 30 barns. An internal support tube can be positioned between the primary absorber and the tubular member as a secondary absorber to enhance neutron absorption, absorber depletion, assembly weight, and assembly heat transfer characteristics.

  7. Advanced Emissions Control Development Program

    SciTech Connect

    G. A. Farthing; G. T. Amrhein; G. A. Kudlac; D. A. Yurchison; D. K. McDonald; M. G. Milobowski

    2001-03-31

    The primary objective of the Advanced Emissions Control Development Program (AECDP) is to develop practical, cost-effective strategies for reducing the emissions of hazardous air pollutants (HAPs, or air toxics) from coal-fired boilers. This objective is being met by identifying ways to effectively control air toxic emissions through the use of conventional flue gas cleanup equipment such as electrostatic precipitators (ESPs), fabric filters (fabric filters), and wet flue gas desulfurization (wet FGD) systems. Development work initially concentrated on the capture of trace metals, hydrogen chloride, and hydrogen fluoride. Recent work has focused almost exclusively on the control of mercury emissions.

  8. ADVANCED EMISSIONS CONTROL DEVELOPMENT PROGRAM

    SciTech Connect

    G.A. Farthing

    2001-02-06

    The primary objective of the Advanced Emissions Control Development Program (AECDP) is to develop practical, cost-effective strategies for reducing the emissions of hazardous air pollutants (HAPs, or air toxics) from coal-fired boilers. The project goal is to effectively control air toxic emissions through the use of conventional flue gas cleanup equipment such as electrostatic precipitators (ESPs), fabric filters (baghouses), and wet flue gas desulfurization (WFGD) systems. Development work initially concentrated on the capture of trace metals, fine particulate, hydrogen chloride, and hydrogen fluoride. Recent work has focused almost exclusively on the control of mercury emissions.

  9. Advanced engineering environment pilot project.

    SciTech Connect

    Schwegel, Jill; Pomplun, Alan R.; Abernathy, Rusty

    2006-10-01

    The Advanced Engineering Environment (AEE) is a concurrent engineering concept that enables real-time process tooling design and analysis, collaborative process flow development, automated document creation, and full process traceability throughout a product's life cycle. The AEE will enable NNSA's Design and Production Agencies to collaborate through a singular integrated process. Sandia National Laboratories and Parametric Technology Corporation (PTC) are working together on a prototype AEE pilot project to evaluate PTC's product collaboration tools relative to the needs of the NWC. The primary deliverable for the project is a set of validated criteria for defining a complete commercial off-the-shelf (COTS) solution to deploy the AEE across the NWC.

  10. Primary care and genetics and genomics.

    PubMed

    Scott, Joan; Trotter, Tracy

    2013-12-01

    With the recent expansion of genetic science, its evolving translation to clinical medicine, and the growing number of available resources for genomics in primary care, the primary care provider must increasingly integrate genetics and genomics into daily practice. Because primary care medicine combines the treatment of acute illness with disease prevention and anticipatory guidance, the primary care provider is in an ideal position to evaluate and treat patients for genetic disease. The notion that genetic knowledge is only rarely needed will have to be replaced with a comprehensive approach that integrates "genetic thinking" into every patient encounter. Genomic competencies will need to be added to the primary care provider's repertoire; such competencies include prevention, assessment, evaluation, and diagnosis of genetic conditions; the ordering and interpreting of genetic tests; communication with families; appropriate referrals; and the management or comanagement of care. The process of deciding when to order genetic tests, what tests to order, and how to interpret the results is complex, and the tests and their results have specific risks and benefits, especially for pediatric patients. The longitudinal nature of primary pediatric care provides the opportunity to obtain and continually update the family history, which is the most powerful initial genetic "test." The ongoing provider-family relationship, coupled with the astounding number of advances in genetic and genomic testing, also necessitates a constant re-evaluation of past diagnosis or nondiagnosis.

  11. The current status of primary hepatocyte culture

    PubMed Central

    Mitaka, Toshihiro

    1998-01-01

    Recently, there have been significant advances toward the development of culture conditions that promote proliferation of primary rodent hepatocytes. There are two major methods for the multiplication of hepatocytes in vitro: one is the use of nicotinamide, the other is the use of a nutrient-rich medium. In the medium containing a high concentration of nicotinamide and a growth factor, primary hepatocytes can proliferate well. In this culture condition small mononucleate cells, which are named small hepatocytes, appear and form colonies. Small hepatocytes have a high potential to proliferate while maintaining hepatic characteristics, and can differentiate into mature ones. On the other hand, combining the nutrient-rich medium with 2% DMSO, the proliferated hepatocytes can recover the hepatic differentiated functions and maintain them for a long time. In this review I describe the culture conditions for the proliferation and differentiation of primary hepatocytes and discuss the small hepatocytes, especially their roles in liver growth. PMID:10319020

  12. Visualizing renal primary cilia.

    PubMed

    Deane, James A; Verghese, Elizabeth; Martelotto, Luciano G; Cain, Jason E; Galtseva, Alya; Rosenblum, Norman D; Watkins, D Neil; Ricardo, Sharon D

    2013-03-01

    Renal primary cilia are microscopic sensory organelles found on the apical surface of epithelial cells of the nephron and collecting duct. They are based upon a microtubular cytoskeleton, bounded by a specialized membrane, and contain an array of proteins that facilitate their assembly, maintenance and function. Cilium-based signalling is important for the control of epithelial differentiation and has been implicated in the pathogenesis of various cystic kidney diseases and in renal repair. As such, visualizing renal primary cilia and understanding their composition has become an essential component of many studies of inherited kidney disease and mechanisms of epithelial regeneration. Primary cilia were initially identified in the kidney using electron microscopy and this remains a useful technique for the high resolution examination of these organelles. New reagents and techniques now also allow the structure and composition of primary cilia to be analysed in detail using fluorescence microscopy. Primary cilia can be imaged in situ in sections of kidney, and many renal-derived cell lines produce primary cilia in culture providing a simplified and accessible system in which to investigate these organelles. Here we outline microscopy-based techniques commonly used for studying renal primary cilia.

  13. Advanced Chemistry Basins Model

    SciTech Connect

    William Goddard; Mario Blanco; Lawrence Cathles; Paul Manhardt; Peter Meulbroek; Yongchun Tang

    2002-11-10

    The DOE-funded Advanced Chemistry Basin model project is intended to develop a public domain, user-friendly basin modeling software under PC or low end workstation environment that predicts hydrocarbon generation, expulsion, migration and chemistry. The main features of the software are that it will: (1) afford users the most flexible way to choose or enter kinetic parameters for different maturity indicators; (2) afford users the most flexible way to choose or enter compositional kinetic parameters to predict hydrocarbon composition (e.g., gas/oil ratio (GOR), wax content, API gravity, etc.) at different kerogen maturities; (3) calculate the chemistry, fluxes and physical properties of all hydrocarbon phases (gas, liquid and solid) along the primary and secondary migration pathways of the basin and predict the location and intensity of phase fractionation, mixing, gas washing, etc.; and (4) predict the location and intensity of de-asphaltene processes. The project has be operative for 36 months, and is on schedule for a successful completion at the end of FY 2003.

  14. Advanced commercial tokamak study

    SciTech Connect

    Thomson, S.L.; Dabiri, A.E.; Keeton, D.C.; Brown, T.G.; Bussell, G.T.

    1985-12-01

    Advanced commercial tokamak studies were performed by the Fusion Engineering Design Center (FEDC) as a participant in the Tokamak Power Systems Studies (TPSS) project coordinated by the Office of Fusion Energy. The FEDC studies addressed the issues of tokamak reactor cost, size, and complexity. A scoping study model was developed to determine the effect of beta on tokamak economics, and it was found that a competitive cost of electricity could be achieved at a beta of 10 to 15%. The implications of operating at a beta of up to 25% were also addressed. It was found that the economics of fusion, like those of fission, improve as unit size increases. However, small units were found to be competitive as elements of a multiplex plant, provided that unit cost and maintenance time reductions are realized for the small units. The modular tokamak configuration combined several new approaches to develop a less complex and lower cost reactor. The modular design combines the toroidal field coil with the reactor structure, locates the primary vacuum boundary at the reactor cell wall, and uses a vertical assembly and maintenance approach. 12 refs., 19 figs.

  15. Advanced Materials and Multifunctional Structures for Aerospace Vehicles

    DTIC Science & Technology

    2006-10-01

    through covalent integration of functional nanotubes ”, Advanced Functional Materials, 14(7) (2004) 643-648. 185 R.Z. Ma, J. Wu, B.Q. Wei, J. Liang, and...on Advanced Materials for Multi Functional Structures in Aerospace Vehicles. The advanced synthesis, processing and the characterization techniques...when more than one primary function is performed either simultaneously or sequentially in time. These systems are based on metallic, ceramic and

  16. Advanced composite structural concepts and materials technologies for primary aircraft structures: Advanced material concepts

    NASA Technical Reports Server (NTRS)

    Lau, Kreisler S. Y.; Landis, Abraham L.; Chow, Andrea W.; Hamlin, Richard D.

    1993-01-01

    To achieve acceptable performance and long-term durability at elevated temperatures (350 to 600 F) for high-speed transport systems, further improvements of the high-performance matrix materials will be necessary to achieve very long-term (60,000-120,000 service hours) retention of mechanical properties and damage tolerance. This report emphasizes isoimide modification as a complementary technique to semi-interpenetrating polymer networks (SIPN's) to achieve greater processibility, better curing dynamics, and possibly enhanced thermo-mechanical properties in composites. A key result is the demonstration of enhanced processibility of isoimide-modified linear and thermo-setting polyimide systems.

  17. Primary vascular access.

    PubMed

    Gibbons, C P

    2006-05-01

    Primary vascular access is usually achievable by a distal autogenous arterio-venous fistula (AVF). This article describes the approach to vascular access planning, the usual surgical options and the factors affecting patency.

  18. Primary infertility (image)

    MedlinePlus

    Primary infertility is a term used to describe a couple that has never been able to conceive a pregnancy ... to do so through unprotected intercourse. Causes of infertility include a wide range of physical as well ...

  19. Parenthood after Primary Infertility.

    ERIC Educational Resources Information Center

    Frances-Fischer, Jana E.; Lightsey, Owen Richard, Jr.

    2003-01-01

    Reviews the literature on the experience of parenting after primary infertility and describes construction and initial testing of an instrument for assessing characteristics of this understudied population. (Contains 52 references and 4 tables.) (GCP)

  20. Primary Nurse - Role Evolution

    ERIC Educational Resources Information Center

    Mundinger, Mary O'Neil

    1973-01-01

    Primary nursing means that each patient has an individual nurse who is responsible for assessing his nursing needs and planning and evaluating his nursing care. The article describes the advantages and problems connected with this approach to patient care. (AG)

  1. Inside the Primary Classroom.

    ERIC Educational Resources Information Center

    Simon, Brian

    1980-01-01

    Presents some of the findings of the ORACLE research program (Observational Research and Classroom Learning Evaluation), a detailed observational study of teacher-student interaction, teaching styles, and management methods within a sample of primary classrooms. (Editor/SJL)

  2. Primary aldosteronism and pregnancy.

    PubMed

    Morton, Adam

    2015-10-01

    Primary aldosteronism is the most common cause of secondary hypertension. Less than 50 cases of pregnancy in women with primary aldosteronism have been reported, suggesting the disorder is significantly underdiagnosed in confinement. Accurate diagnosis is complicated by physiological changes in the renin-angiotensin-aldosterone axis in pregnancy, leading to a risk of false negative results on screening tests. The course of primary aldosteronism during pregnancy is highly variable, although overall it is associated with a very high risk of fetal and maternal morbidity and mortality. The optimal management of primary aldosteronism during pregnancy is unclear, with uncertainty regarding the safety of mineralocorticoid antagonists and amiloride, their relative efficacy compared with the antihypertensive medications commonly used during pregnancy, and as to whether prognosis is improved by laparoscopic adrenalectomy where an adrenal adenoma can be demonstrated.

  3. Primary biliary cirrhosis

    MedlinePlus

    ... medlineplus.gov/ency/article/000282.htm Primary biliary cirrhosis To use the sharing features on this page, ... and leads to scarring of the liver called cirrhosis. This is called biliary cirrhosis. Causes The cause ...

  4. Familial glaucoma iridogoniodysplasia maps to a 6p25 region implicated in primary congenital glaucoma and iridogoniodysgenesis anomaly.

    PubMed Central

    Jordan, T; Ebenezer, N; Manners, R; McGill, J; Bhattacharya, S

    1997-01-01

    Familial glaucoma iridogoniodysplasia (FGI) is a form of open-angle glaucoma in which developmental anomalies of the iris and irido-corneal angle are associated with a juvenile-onset glaucoma transmitted as an autosomal dominant trait. A single large family with this disorder was examined for genetic linkage to microsatellite markers. A peak LOD score of 11.63 at a recombination fraction of 0 was obtained with marker D6S967 mapping to chromosome 6p25. Haplotype analysis places the disease gene in a 6.4-cM interval between the markers D6S1713 and D6S1600. Two novel clinical appearances extend the phenotypic range and provide evidence of variable expressivity. The chromosome 6p25 region is now implicated in FGI, primary congenital glaucoma, and iridogoniodysgenesis anomaly. This may indicate the presence of a common causative gene or, alternatively, a cluster of genes involved in eye development/function. Images Figure 2 PMID:9382099

  5. Primary actinomycosis of hand

    PubMed Central

    Padhi, Sanghamitra; Dash, Muktikesh; Turuk, Jyotirmayee; Sahu, Rani; Panda, Pritilata

    2014-01-01

    Actinomycosis is a chronic granulomatous suppurative disease having the propensity for extension to the contagious tissue with the formation of multiple discharging sinus tracts. Primary actinomycosis of extremity is a very uncommon clinical entity and is commonly considered as a soft-tissue infection. We report here, a case of primary actinomycosis of the upper extremity in a 24-year-old male who was treated successfully with surgical excision and extended period of antimicrobial treatment. PMID:25538911

  6. Primary headache disorders.

    PubMed

    Benoliel, Rafael; Eliav, Eli

    2013-07-01

    Primary headache disorders include migraine, tension-type headaches, and the trigeminal autonomic cephalgias (TACs). "Primary" refers to a lack of clear underlying causative pathology, trauma, or systemic disease. The TACs include cluster headache, paroxysmal hemicrania, and short-lasting neuralgiform headache attacks with conjunctival injection and tearing; hemicrania continua, although classified separately by the International Headache Society, shares many features of both migraine and the TACs. This article describes the features and treatment of these disorders.

  7. Primary vitreoretinal lymphoma

    PubMed Central

    Mulay, Kaustubh; Narula, Ritesh; Honavar, Santosh G

    2015-01-01

    Primary vitreoretinal lymphoma (PVRL) is an uncommon, but potentially fatal intraocular malignancy, which may occur with or without primary central nervous system lymphoma (PCNSL). Considered to be a subset of PCNSL, it is mostly of diffuse large B-cell type. The diagnosis of PVRL poses a challenge not only to the clinician, but also to the pathologist. Despite aggressive treatment with chemotherapy and/or radiotherapy, relapses or CNS involvement are common. PMID:25971162

  8. Primary care research ethics.

    PubMed Central

    Jones, R; Murphy, E; Crosland, A

    1995-01-01

    Research activity in primary care is increasing rapidly, and raises a range of specific ethical issues. Many of these relate to the involvement of individuals in the community who are not seeking medical care and to the impact of research participation on relationships between general practitioners and their patients. The ethical issues pertinent to a range of quantitative and qualitative research methodologies in primary care are identified and considered. PMID:8554844

  9. Primary biliary cirrhosis.

    PubMed

    Carey, Elizabeth J; Ali, Ahmad H; Lindor, Keith D

    2015-10-17

    Primary biliary cirrhosis is a chronic cholestatic liver disease characterised by destruction of small intrahepatic bile ducts, leading to fibrosis and potential cirrhosis through resulting complications. The serological hallmark of primary biliary cirrhosis is the antimitochondrial antibody, a highly disease-specific antibody identified in about 95% of patients with primary biliary cirrhosis. These patients usually have fatigue and pruritus, both of which occur independently of disease severity. The typical course of primary biliary cirrhosis has changed substantially with the introduöction of ursodeoxycholic acid (UDCA). Several randomised placebo-controlled studies have shown that UDCA improves transplant-free survival in primary biliary cirrhosis. However, about 40% of patients do not have a biochemical response to UDCA and would benefit from new therapies. Liver transplantation is a life-saving surgery with excellent outcomes for those with decompensated cirrhosis. Meanwhile, research on nuclear receptor hormones has led to the development of exciting new potential treatments. This Seminar will review the current understanding of the epidemiology, pathogenesis, and natural history of primary biliary cirrhosis, discuss management of the disease and its sequelae, and introduce research on new therapeutic options.

  10. Primary cerebral malignant melanoma

    PubMed Central

    Tang, Kai; Kong, Xiangyi; Mao, Gengsheng; Qiu, Ming; Zhu, Haibo; Zhou, Lei; Nie, Qingbin; Xu, Yi; Du, Shiwei

    2017-01-01

    Abstract Primary intracranial melanomas are uncommon and constitute approximately 1% of all melanoma cases and 0.07% of all brain tumors. In nature, these primary melanomas are very aggressive and can spread to other organs. We report an uncommon case of primary cerebral malignant melanoma—a challenging diagnosis guided by clinical presentations, radiological features, and surgical biopsy results, aiming to emphasize the importance of considering primary melanoma when making differential diagnoses of intracranial lesions. We present a rare case of a primary cerebral melanoma in the left temporal lobe. The mass appeared iso-hypodense on brain computed tomography (CT), short signal on T1-weighted magnetic resonance images (T1WI) and long signal on T2WI. It was not easy to make an accurate diagnosis before surgery. We showed the patient's disease course and reviewed related literatures, for readers’ reference. Written informed consent was obtained from the patient for publication of this case report and any accompanying images. Because of this, there is no need to conduct special ethic review and the ethical approval is not necessary. After surgery, the pathological examination confirmed the diagnosis of melanoma. The patient was discharged without any complications and went on to receive adjuvant radiochemotherapy. It is difficult to diagnose primary cerebral melanoma in the absence of any cutaneous melanosis. A high index of clinical suspicion along with good pathology reporting is the key in diagnosing these extremely rare tumors. PMID:28121927

  11. Classification of primary articular chondrocalcinosis.

    PubMed

    Zitnan, D; Sitaj, S

    1979-01-01

    Based on long-term observations the authors submit a categorization of primary (hereditary and solitary) articular chondrocalcinosis into three different sub-populations. Attention is drawn to the fact that the extent of the qualitative disorder of the articular cartilage, obviously conditioned genetically, is linked with the age factor and determines the quantitative differences of pyrophosphate arthropathy in primary chondrocalcinosis. In young age, as a rule in the third decade, severe polyarticular condrocalcinosis (first sub-population) develops which causes relatively soon invalidity, in middle age (5th and 6th decade) milder condrocalcinosis develops (second sub-population) which combines with extraarticular, tendinous and tissue calcifacations, and finally in advanced age oligoarticular chondrocalcinosis develops (third sub-population) which is usually associated with ankylosing hyperostosis of the spine. Articular chondrocalcinosis (CCA) which we described by this term as a special metabolic arthropathy which occurs in families and solitary and which we defined as a special nosological unit (35, 36,) has become generally known and firmly established in rheumatology. As ensues from numerous publications, primary (idiopathic) CCA which comprises the hereditary and solitary (sporadic) form is characterized by pyrophosphate arthropathy which develops on articular cartilages not damaged by another process (13, 25, 26, 37); on the other hand as secondary CCA we consider pyrophosphate arthropathies which are associated with metabolic, endocrine or other diseases (9, 30). The common sign of both basic forms of CCA is the presence of microcrystals of calcium pyrophosphate dihydrate (CaPD) in articular cartilages, synovial fluid, or other articular structures (capsules, tendons, ligaments), characterized originally by McCarty et al. (11, 18) and later by other authors (2, 23, 27, 32). In addition to semantic (terminological) problems there were also questions of the

  12. Advanced Microwave/Millimeter-Wave Imaging Technology

    NASA Astrophysics Data System (ADS)

    Shen, Zuowei; Yang, Lu; Luhmann, N. C., Jr.; Domier, C. W.; Ito, N.; Kogi, Y.; Liang, Y.; Mase, A.; Park, H.; Sakata, E.; Tsai, W.; Xia, Z. G.; Zhang, P.

    Millimeter wave technology advances have made possible active and passive millimeter wave imaging for a variety of applications including advanced plasma diagnostics, radio astronomy, atmospheric radiometry, concealed weapon detection, all-weather aircraft landing, contraband goods detection, harbor navigation/surveillance in fog, highway traffic monitoring in fog, helicopter and automotive collision avoidance in fog, and environmental remote sensing data associated with weather, pollution, soil moisture, oil spill detection, and monitoring of forest fires, to name but a few. The primary focus of this paper is on technology advances which have made possible advanced imaging and visualization of magnetohydrodynamic (MHD) fluctuations and microturbulence in fusion plasmas. Topics of particular emphasis include frequency selective surfaces, planar Schottky diode mixer arrays, electronically controlled beam shaping/steering arrays, and high power millimeter wave local oscillator and probe sources.

  13. Reliability assurance for regulation of advanced reactors

    SciTech Connect

    Fullwood, R.; Lofaro, R.; Samanta, P.

    1991-12-31

    The advanced nuclear power plants must achieve higher levels of safety than the first generation of plants. Showing that this is indeed true provides new challenges to reliability and risk assessment methods in the analysis of the designs employing passive and semi-passive protection. Reliability assurance of the advanced reactor systems is important for determining the safety of the design and for determining the plant operability. Safety is the primary concern, but operability is considered indicative of good and safe operation. This paper discusses several concerns for reliability assurance of the advanced design encompassing reliability determination, level of detail required in advanced reactor submittals, data for reliability assurance, systems interactions and common cause effects, passive component reliability, PRA-based configuration control system, and inspection, training, maintenance and test requirements. Suggested approaches are provided for addressing each of these topics.

  14. Health promotion and primary health care: examining the discourse.

    PubMed

    Ashcroft, Rachelle

    2015-01-01

    The health promotion discourse is comprised of assumptions about health and health care that are compatible with primary health care. An examination of the health promotion discourse illustrates how assumptions of health can help to inform primary health care. Despite health promotion being a good fit for primary health care, this analysis demonstrates that the scope in which it is being implemented in primary health care settings is limited. The health promotion discourse appears largely compatible with primary health care-in theory and in the health care practices that follow. The aim of this article is to contribute to the advancement of theoretical understanding of the health promotion discourse, and the relevance of health promotion to primary health care.

  15. Other primary headaches

    PubMed Central

    Bahra, Anish

    2012-01-01

    The ‘Other Primary Headaches’ include eight recognised benign headache disorders. Primary stabbing headache is a generally benign disorder which often co-exists with other primary headache disorders such as migraine and cluster headache. Primary cough headache is headache precipitated by valsalva; secondary cough has been reported particularly in association with posterior fossa pathology. Primary exertional headache can occur with sudden or gradual onset during, or immediately after, exercise. Similarly headache associated with sexual activity can occur with gradual evolution or sudden onset. Secondary headache is more likely with both exertional and sexual headache of sudden onset. Sudden onset headache, with maximum intensity reached within a minute, is termed thunderclap headache. A benign form of thunderclap headache exists. However, isolated primary and secondary thunderclap headache cannot be clinically differentiated. Therefore all headache of thunderclap onset should be investigated. The primary forms of the aforementioned paroxysmal headaches appear to be Indomethacin sensitive disorders. Hypnic headache is a rare disorder which is termed ‘alarm clock headache’, exclusively waking patients from sleep. The disorder can be Indomethacin responsive, but can also respond to Lithium and caffeine. New daily persistent headache is a rare and often intractable headache which starts one day and persists daily thereafter for at least 3 months. The clinical syndrome more often has migrainous features or is otherwise has a chronic tension-type headache phenotype. Management is that of the clinical syndrome. Hemicrania continua straddles the disorders of migraine and the trigeminal autonomic cephalalgias and is not dealt with in this review. PMID:23024566

  16. Primary care development zones.

    PubMed

    Beardshaw, V; Gordon, P; Plamping, D

    1993-01-30

    Most commentators on the Tomlinson report have agreed with its emphasis on improving primary and community care. The three elements of such a strategy are a remedial programme to bring primary care up to national standards, a programme to provide such services to people with non-standard needs such as mobile Londoners, ethnic minorities, and homeless people, and the development of an expanded model of primary care. No one model will be appropriate across all of London. The process should start with an audit of existing resources and services within each community, together with an analysis of needs. From this would develop a local programme with specific plans for investment in premises, staffing, training, and management. New contractual mechanisms may be needed to attract practitioners, improve their premises, secure out of hours services, and provide medical cover for community beds. There should also be incentives for closer working between primary and secondary services. No developments on the scale needed for London have been carried out in primary care within the lifetime of the NHS--but their success will be critical to the calibre of health services for Londoners into the next century.

  17. Primary Care of the Solid Organ Transplant Recipient.

    PubMed

    Wong, Christopher J; Pagalilauan, Genevieve

    2015-09-01

    Solid organ transplantation (SOT) is one of the major advances in medicine. Care of the SOT recipient is complex and continued partnership with the transplant specialist is essential to manage and treat complications and maintain health. The increased longevity of SOT recipients will lead to their being an evolving part of primary care practice, with ever more opportunities for care, education, and research of this rewarding patient population. This review discusses the overall primary care management of adult SOT recipients.

  18. Advanced planetary studies

    NASA Technical Reports Server (NTRS)

    1977-01-01

    Results of planetary advanced studies and planning support are summarized. The scope of analyses includes cost estimation research, planetary mission performance, penetrator advanced studies, Mercury mission transport requirements, definition of super solar electric propulsion/solar sail mission discriminators, and advanced planning activities.

  19. Advances in forefoot trauma.

    PubMed

    Clements, J Randolph; Schopf, Robert

    2013-07-01

    Forefoot traumas, particularly involving the metatarsals, are commonly occurring injuries. There have been several advances in management of these injuries. These advances include updates in operative technique, internal fixation options, plating constructs, and external fixation. In addition, the advances of soft tissue management have improved outcomes. This article outlines these injuries and provides an update on techniques, principles, and understanding of managing forefoot trauma.

  20. Primary lymphoma of the brain

    MedlinePlus

    Brain lymphoma; Cerebral lymphoma; Primary lymphoma of the central nervous system; Lymphoma - brain ... The cause of primary brain lymphoma is not known. People with a weakened immune system are at high risk for primary lymphoma of the brain. ...

  1. Primary hepatic carcinoid tumor.

    PubMed

    Gao, Jinbo; Hu, Zhijian; Wu, Junwei; Bai, Lishan; Chai, Xinqun

    2011-11-19

    Primary hepatic carcinoid tumor is rare and poses a challenge for diagnosis and management. We presented a case of primary hepatic carcinoid tumor in a 53-year-old female with a complaint of right upper abdominal pain. Computer tomography scans revealed a hypervascular mass in segment 4 of the liver. An ultrasonography-guided biopsy showed a carcinoid tumor. No other lesions were found by the radiological investigations. Surgery resection was performed and histopathological examination revealed a primary hepatic carcinoid tumor. Three years later, recurrence was found and transcatheter arterial chemoembolization was performed. After transcatheter arterial chemoembolization, the patient has been free of symptom and had no radiological disease progression for over 6 months. Surgical resection combination with transcatheter arterial chemoembolization is effective to offer excellent palliation.

  2. Plume primary smoke

    NASA Astrophysics Data System (ADS)

    Chastenet, J. C.

    1993-06-01

    The exhaust from a solid propellant rocket motor usually contains condensed species. These particles, also called 'Primary Smoke', are often prejudicial to missile detectability and to the guidance system. To avoid operational problems it is necessary to know and quantify the effects of particles on all aspects of missile deployment. A brief description of the origin of the primary smoke is given. It continues with details of the interaction between particles and light as function of both particles and light properties (nature, size, wavelength, etc). The effects of particles on plume visibility, attenuation of an optical beam propagated through the plume and the contribution of particles on optical signatures of the plume are also described. Finally, various methods used in NATO countries to quantify the primary smoke effects are discussed.

  3. [Primary care in Ireland].

    PubMed

    Sánchez-Sagrado, T

    2017-03-27

    Spanish doctors are still leaving the country to look for quality work. Ireland is not a country with many Spanish professionals but it is interesting to know its particular Health care system. Ireland is one of the countries with a national health care system, although it has a mixture of private health care insurance schemes. People have a right to health care if they have been living in Ireland at least for a year. Access to the primary care health system depends on age and income: free of charge for Category 1 and co-payments for the rest. This division generates great inequalities among the population. Primary Care doctors are self-employed, and they work independently. However, since 2001 they have tended to work in multidisciplinary teams in order to strengthen the Primary Care practice. Salary is gained from a combination of public and private incomes which are not differentiated. The role of the General Practitioner consists in the treatment of acute and chronic diseases, minor surgery, child care, etc. There is no coordination between Primary and Secondary care. Access to specialised medicine is regulated by the price of consultation. Primary Care doctors are not gatekeepers. To be able to work here, doctors must have three years of training after medical school. After that, Continuing Medical Education is compulsory, and the college of general practitioners monitors it annually. The Irish health care system does not fit into the European model. Lack of a clear separation between public and private health care generates great inequalities. The non-existence of coordination between primary and specialised care leads to inefficiencies, which Ireland cannot allow itself after a decade of economic crisis.

  4. Session: CSP Advanced Systems -- Advanced Overview (Presentation)

    SciTech Connect

    Mehos, M.

    2008-04-01

    The project description is: (1) it supports crosscutting activities, e.g. advanced optical materials, that aren't tied to a single CSP technology and (2) it supports the 'incubation' of new concepts in preliminary stages of investigation.

  5. Primary appendiceal mucinous adenocarcinoma.

    PubMed

    Behera, Prativa Kumari; Rath, Pramod Kumar; Panda, Rabiratna; Satpathi, Sanghamitra; Behera, Rajan

    2011-04-01

    Primary Adenocarcinomas of the appendix are extremely rare tumor. We report a case of primary mucinous adenocarcinoma in a 40 year old lady misdiagnosed as having acute appendicitis. All the routine investigations were within normal limit. USG of abdomen showed dilated appendix with little fluid collection adjacent to it and no other abnormality was seen which suggested acute appendicitis. Appendicectomy was done and excised appendix was sent for histopathological examination. Mucinous Adenocarcinoma of the appendix was confirmed after histopathological examination. Right hemicolectomy was done as a second stage procedure. As some cases are incidentally discovered, this case emphasizes that histological examination of all appendicectomy specimens is mandatory.

  6. Does primary fibromyalgia exist?

    PubMed

    Forslind, K; Fredriksson, E; Nived, O

    1990-10-01

    Twenty-one of 25 consecutive primary fibromyalgia or fibrositis patients, identified during a 5-year period in a tertiary care day-ward for pain syndromes, were re-examined. Fifteen fulfilled criteria for fibromyalgia but unexpectedly, all cases had either psychiatric disturbance or thyroid dysfunction. Of the four patients not seen at follow-up, two had developed neurological diseases, another rheumatoid arthritis and one other hypothyroidism. Thus, after 5 years no patient fulfilled the criteria for primary fibromyalgia. Women occupied as manual workers were over-represented. Most patients reported beneficial effects of physiotherapy. None of the patients has been able to return to full time work.

  7. Fibrositis and primary hypothyroidism.

    PubMed

    Carette, S; Lefrançois, L

    1988-09-01

    The prevalence of fibrositis was determined in 100 patients with subclinical or biochemical primary hypothyroidism. Nineteen patients reported symptoms of joint and/or muscle pain with stiffness. Five of these patients presented 7 or more tender points on examination, thus allowing a diagnosis of fibrositis to be made in only 5% of the total group. Symptomatic improvement after thyroid hormone replacement occurred in 10 of the 19 patients, including 3 of those with fibrositis. There were no significant changes in tender points. Our data indicate that fibrositis is uncommon in patients with primary hypothyroidism despite the frequent occurrence of symptoms suggestive of this syndrome.

  8. Melatonin for primary insomnia?

    PubMed

    2009-07-01

    Melatonin, a hormone produced by the pineal gland, has a key role in regulating circadian rhythms, most importantly, the sleep-wake cycle. Melatonin's action has led to its being tried as a treatment for a wide range of sleep disorders, such as jet lag, primary insomnia, sleep-wake cycle disruption and sleep problems in children with neuro-developmental disorders. Until recently, it had not been licensed in the UK for any indication. Prolonged-release melatonin (Circadin - Lundbeck) has now been licensed as a treatment for primary insomnia. Here we consider whether this product has a place in the management of people with this condition.

  9. Advanced Propulsion Physics Lab: Eagleworks Investigations

    NASA Technical Reports Server (NTRS)

    Scogin, Tyler

    2014-01-01

    Eagleworks Laboratory is an advanced propulsions physics laboratory with two primary investigations currently underway. The first is a Quantum Vacuum Plasma Thruster (QVPT or Q-thrusters), an advanced electric propulsion technology in the development and demonstration phase. The second investigation is in Warp Field Interferometry (WFI). This is an investigation of Dr. Harold "Sonny" White's theoretical physics models for warp field equations using optical experiments in the Electro Optical laboratory (EOL) at Johnson Space Center. These investigations are pursuing technology necessary to enable human exploration of the solar system and beyond.

  10. Advances in Immunotherapy for Glioblastoma Multiforme

    PubMed Central

    Huang, Boyuan; Zhang, Hongbo; Ye, Bainxin

    2017-01-01

    Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults. Patients with GBM have poor outcomes, even with the current gold-standard first-line treatment: maximal safe resection combined with radiotherapy and temozolomide chemotherapy. Accumulating evidence suggests that advances in antigen-specific cancer vaccines and immune checkpoint blockade in other advanced tumors may provide an appealing promise for immunotherapy in glioma. The future of therapy for GBM will likely incorporate a combinatorial, personalized approach, including current conventional treatments, active immunotherapeutics, plus agents targeting immunosuppressive checkpoints. PMID:28299344

  11. Advanced Electrical Materials and Component Development

    NASA Technical Reports Server (NTRS)

    Schwarze, Gene E.

    2003-01-01

    The primary means to develop advanced electrical components is to develop new and improved materials for magnetic components (transformers, inductors, etc.), capacitors, and semiconductor switches and diodes. This paper will give a description and status of the internal and external research sponsored by NASA Glenn Research Center on soft magnetic materials, dielectric materials and capacitors, and high quality silicon carbide (SiC) atomically smooth substrates. The rationale for and the benefits of developing advanced electrical materials and components for the PMAD subsystem and also for the total power system will be briefly discussed.

  12. The SPARC-related modular calcium binding protein 2 (SMOC2) gene polymorphism in primary glaucoma: a case-control study

    PubMed Central

    Al-Dabbagh, Najwa; Al-Shahrani, Hamoud; Al-Dohayan, Nourah; Mustafa, Md; Arfin, Misbahul; Al-Asmari, Abdulrahman K

    2017-01-01

    Primary glaucomas are among the most common eye diseases that may potentially result in bilateral blindness. Both genetics and environmental factors are reported to be involved in the etiology of primary glaucomas. Secreted protein acidic and rich in cysteine (SPARC)-related modular calcium binding protein 2 (SMOC2) is a matricellular glycoprotein encoded by the SMOC2 gene and known to regulate the expression of extracellular matrix (ECM) proteins and matrix metalloproteinases (MMPs), which play an important role in the pathogenesis of primary glaucomas. The frequencies of alleles and genotypes of SMOC2 variants were examined in 406 Saudi subjects, including primary open angle glaucoma (POAG, n=140) and primary angle closure glaucoma (PACG, n=64) patients and 202 matched healthy controls using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Genotyping of SMOC2 polymorphism (rs13208776) revealed a significantly higher frequency of the heterozygous genotype GA (P<0.01) and a lower frequency of wild type GG genotype (P=0.05) in glaucoma patients compared to the controls. Upon stratification of the patients on the basis of types of glaucoma, PACG patients had a significantly higher frequency of GA genotype as compared to the controls (P<0.01), whereas there was no significant difference between the POAG patient and control groups in frequencies of SMOC2 alleles and genotypes. Further, there was no significant difference in frequency distribution of alleles and genotypes between male and female patients. This study indicates that the GA genotype of SMOC2 (G>A) polymorphism is significantly associated with PACG and may be a risk factor. However, further large-scale studies in the Saudi population as well as in other ethnic populations are needed to confirm this association. PMID:28356709

  13. Exclusion of primary congenital glaucoma (PCG) from two candidate regions of chromosomes 1 and 6

    SciTech Connect

    Sarfarazi, M.; Akarsu, A.N.; Barsoum-Homsy, M.

    1994-09-01

    PCG is a genetically heterogeneous condition in which a significant proportion of families inherit in an autosomally recessive fashion. Although association of PCG with chromosomal abnormalities has been repeatedly reported in the literature, the chromosomal location of this condition is still unknown. Therefore, this study is designed to identify the chromosomal location of the PCG locus by positional mapping. We have identified 80 PCG families with a total of 261 potential informative meiosis. A group of 19 pedigrees with a minimum of 2 affected children in each pedigree and consanguinity in most of the parental generation were selected as our initial screening panel. This panel consists of a total of 44 affected and 93 unaffected individuals giving a total of 99 informative meiosis, including 5 phase-known. We used polymerase chain reaction (PCR), denaturing polyacrylamide gels and silver staining to genotype our families. We first screened for markers on 1q21-q31, the reported location for juvenile primary open-angle glaucoma and excluded a region of 30 cM as the likely site for the PCG locus. Association of PCG with both ring chromosome 6 and HLA-B8 has also been reported. Therefore, we genotyped our PCG panel with PCR applicable markers from 6p21. Significant negative lod scores were obtained for D6S105 (Z = -18.70) and D6S306 (Z = -5.99) at {theta}=0.001. HLA class 1 region has also contained one of the tubulin genes (TUBB) which is an obvious candidate for PCG. Study of this gene revealed a significant negative lod score with PCG (Z = -16.74, {theta}=0.001). A multipoint linkage analysis of markers in this and other regions containing the candidate genes will be presented.

  14. Primary Creative Writing.

    ERIC Educational Resources Information Center

    Wooten, Vida Jo

    1968-01-01

    Children will enjoy creative writing in the primary grades if they are given inspiration, time to write, and the opportunity to share their work with classmates. A second-grade class began a creative writing project by listening to poetry and selecting poems to memorize and recite. This stimulated and encouraged them to evaluate and to write…

  15. Healthcare is primary.

    PubMed

    Kumar, Raman

    2015-01-01

    India is undergoing a rapid transformation in terms of governance, administrative reforms, newer policy develoment, and social movements. India is also considered one of the most vibrant economies in the world. The current discourse in public space is dominated by issues such as economic development, security, corruption free governance, gender equity, and women safety. Healthcare though remains a pressing need of population; seems to have taken a backseat. In the era of decreasing subsidies and cautious investment in social sectors, the 2(nd) National Conference on Family Medicine and Primary Care 2015 (FMPC) brought a focus on "healthcare" in India. The theme of this conference was "Healthcare is Primary." The conference participants discussed on the theme of why healthcare should be a national priority and why strong primary care should remain at the center of healthcare delivery system. The experts recommended that India needs to strengthen the "general health system" instead of focusing on disease based vertical programs. Public health system should have capacity and skill pool to be able to deliver person centered comprehensive health services to the community. Proactive implementation of policies towards human resource in health is the need of the hour. As the draft National Health Policy 2015 is being debated, "family medicine" (academic primary care), the unfinished agenda of National Health Policy 2002, remains a priority area of implementation.

  16. Beginning Primary Teaching

    ERIC Educational Resources Information Center

    Jacklin, Angela; Griffiths, Vivienne; Robinson, Carol

    2006-01-01

    This book supports primary teachers' early professional development and learning, tackling key questions and concerns that new teachers might face in their early careers, such as: How will I get through the first term? When will I feel like a "real" teacher? What can I expect from my first years in teaching? Drawing on the experiences of beginning…

  17. New Primary School Syllabus.

    ERIC Educational Resources Information Center

    Ministry of Education and Culture (Trinidad and Tobago).

    This official syllabus of Trinidad and Tobago's primary schools gives detailed guidelines on the teaching objectives of each curriculum area and how these can best be realized, as well as descriptions of the subject matter. The curriculum is divided into three levels: Level I (5- to 7-year-olds), Level II (7- to 9-year-olds) and Level III (10+- to…

  18. Primary diffuse leptomeningeal gliosarcomatosis.

    PubMed

    Moon, Ju Hyung; Kim, Se Hoon; Kim, Eui Hyun; Kang, Seok-Gu; Chang, Jong Hee

    2015-04-01

    Primary diffuse leptomeningeal gliomatosis (PDLG) is a rare condition with a fatal outcome, characterized by diffuse infiltration of the leptomeninges by neoplastic glial cells without evidence of primary tumor in the brain or spinal cord parenchyma. In particular, PDLG histologically diagnosed as gliosarcoma is extremely rare, with only 2 cases reported to date. We report a case of primary diffuse leptomeningeal gliosarcomatosis. A 68-year-old man presented with fever, chilling, headache, and a brief episode of mental deterioration. Initial T1-weighted post-contrast brain magnetic resonance imaging (MRI) showed diffuse leptomeningeal enhancement without a definite intraparenchymal lesion. Based on clinical and imaging findings, antiviral treatment was initiated. Despite the treatment, the patient's neurologic symptoms and mental status progressively deteriorated and follow-up MRI showed rapid progression of the disease. A meningeal biopsy revealed gliosarcoma and was conclusive for the diagnosis of primary diffuse leptomeningeal gliosarcomatosis. We suggest the inclusion of PDLG in the potential differential diagnosis of patients who present with nonspecific neurologic symptoms in the presence of leptomeningeal involvement on MRI.

  19. Pediatric primary gastric lymphoma.

    PubMed

    Harris, G J; Laszewski, M J

    1992-04-01

    Primary gastric lymphoma in the pediatric population is rare. We have described a case of non-Hodgkin's lymphoma (Burkitt's type) manifested as a gastric mass. Despite its rarity in children, this tumor should be treated aggressively, since long-term survival has been reported.

  20. Primary Biliary Cirrhosis

    MedlinePlus

    ... of liver cancer every 6 to 12 months. Health care providers use blood tests, ultrasound, or both to check for signs of ... make the diagnosis of primary biliary cirrhosis. A health care provider uses the test selectively when he or she is concerned that ...

  1. Primary Standards Laboratory report

    SciTech Connect

    Not Available

    1990-12-01

    Sandia National Laboratories operates the Primary Standards Laboratory (PSL) for the Department of Energy, Albuquerque Operations Office (DOE/AL). This report summarizes metrology activities that received emphasis in the first half of 1990 and provides information pertinent to the operation of the DOE/AL system-wide Standards and Calibration Program.

  2. Primary Premier for Belfast

    ERIC Educational Resources Information Center

    McAlister, Peter

    2009-01-01

    The author talks about the Association for Science Education (ASE) Primary Science Committee's (PSC) March 2009 meeting which was held in Belfast as guests of ASE Northern Ireland. To mark the auspicious occasion of a body that usually meets four times a year in the Hatfield HQ crossing the Irish Sea to be hosted by its Celtic cousins, a Lord…

  3. From Primary to Secondary

    ERIC Educational Resources Information Center

    Anderson, Lyn

    2011-01-01

    This author discusses her decision to move to secondary school to teach mathematics, after having taught and been a mathematics manager in primary schools for six years. She states that this was a valuable experience and sparked her interest in the transition experiences of students, particularly in mathematics. Research (Evangelou et al, 2008,…

  4. Primary Art Resource Guide.

    ERIC Educational Resources Information Center

    Newton Unified School District 373, KS.

    GRADES OR AGES: Primary Grades. SUBJECT MATTER: Art. ORGANIZATION AND PHYSICAL APPEARANCE: The guide begins with a list of topics for art expression. The main body of the guide contains 15 color-coded sections on the following subjects: 1) mobiles and folded paper; 2) collage and photo montage; 3) square paper and mosaics; 4) wax paper and…

  5. Primary ectopic frontotemporal craniopharyngioma

    PubMed Central

    Ortega-Porcayo, Luis Alberto; Ponce-Gómez, Juan Antonio; Martínez-Moreno, Mauricio; Portocarrero-Ortíz, Lesly; Tena-Suck, Martha Lilia; Gómez-Amador, Juan Luis

    2015-01-01

    Introduction Primary ectopic craniopharyngiomas have only rarely been reported. Craniopharyngiomas involve usually the sellar and suprasellar region, but can be originated from cell remnants of the obliterated craniopharyngeal duct or metaplastic change of andenohypophyseal cells. We present the first case of a primary ectopic frontotemporal craniopharyngioma. Presentation of case A 35-year old woman presented with a one-year history of headache and diplopia. MRI showed a large frontotemporal cystic lesion. Tumor resection was performed with a keyhole endoscopic frontal lateral approach. The pathological features showed an adamantinomatous craniopharyngioma with a cholesterol granuloma reaction. Discussion There have been reported different localizations for primary ectopic craniopharyngioma. Our case presented a lobulated frontotemporal cystic mass formed by a dense eosinophilic proteinaceous material dystrophic calcifications and cholesterol crystals, with epithelial remnants. No tumor regrowth was observed in the magnetic resonance image 27 months postoperatively. Conclusion Primary ectopic craniopharyngioma is a rare entity with a pathogenesis that remains uncertain. This is an unusual anatomic location associated with unique clinical findings. PMID:25725331

  6. Philosophy in Primary Schools?

    ERIC Educational Resources Information Center

    White, John

    2012-01-01

    The article is a critical discussion of the aims behind the teaching of philosophy in British primary schools. It begins by reviewing the recent Special Issue of the "Journal of Philosophy of Education" Vol 45 Issue 2 2011 on "Philosophy for Children in Transition", so as to see what light this might throw on the topic just…

  7. Multiple Primary Cancer Monograph

    Cancer.gov

    To identify groups of cancer survivors that are at increased risk for multiple primary cancers, investigators led an effort to provide the first comprehensive population-based analysis of the risk of subsequent cancer in the U.S., resulting in a monograph.

  8. Implementation of Advanced Access in a Family Medicine Residency Practice.

    PubMed

    Tseng, Ann; Wiser, Eric; Barclay, Emily; Aiello, Karen

    2015-01-01

    Several models of scheduling have been documented in the literature, including the traditional model, the carve-out model, and the advanced access model. We describe the implementation of the advanced access model in our clinic, which has been very successful. Advanced access has decreased third next available appointments to less than seven days for many of our providers and has increased individual primary care physician continuity for 40% of our providers. Interestingly, we had no gains in patient satisfaction, which is consistent with other previously published studies on advanced access.

  9. GWAS in Primary Biliary Cirrhosis

    PubMed Central

    Gulamhusein, Aliya F.; Juran, Brian D.

    2015-01-01

    Genome wide association studies (GWAS) have been a significant technological advance in our ability to evaluate the genetic architecture of complex diseases such as Primary Biliary Cirrhosis (PBC). To date, six large-scale studies have been performed which identified 27 non-HLA risk loci associated with PBC. The identified risk variants emphasize important disease concepts; namely, that disturbances in immunoregulatory pathways are important in the pathogenesis of PBC and that such perturbations are shared among a diverse number of autoimmune diseases – suggesting the risk architecture may confer a generalized propensity to autoimmunity not necessarily specific to PBC. Furthermore, the impact of non-HLA risk variants, particularly in genes involved with IL-12 signaling, and ethnic variation in conferring susceptibility to PBC have been highlighted. While GWAS have been a critical stepping-stone in understanding common genetic variation contributing to PBC, limitations pertaining to power, sample availability, and strong linkage disequilibrium across genes have left us with an incomplete understanding of the genetic underpinnings of disease pathogenesis. Future efforts to gain insight into this missing heritability, the genetic variation that contributes to important disease outcomes and the functional consequences of associated variants will be critical if practical clinical translation is to be realized. PMID:26676814

  10. Restoring primary anterior teeth.

    PubMed

    Waggoner, William F

    2002-01-01

    A variety of esthetic restorative materials are available for restoring primary incisors. Knowledge of the specific strengths, weakness, and properties of each material will enhance the clinician's ability to make the best choice of selection for each individual situation. Intracoronal restorations of primary teeth may utilize resin composites, glass ionomer cements, resin-modified ionomers, or polyacid-modified resins. Each has distinct advantages and disadvantages and the clinical conditions of placement may be a strong determining factor as to which material is utilized. Full coronal restoration of primary incisors may be indicated for a number of reasons. Crowns available for restoration of primary incisors include those that are directly bonded onto the tooth, which generally are a resin material, and those crowns that are luted onto the tooth and are some type of stainless steel crown. However, due to lack of supporting clinical data, none of the crowns can be said to be superior to the others under all circumstances. Though caries in the mandibular region is rare, restorative solutions for mandibular incisors are needed. Neither stainless steel crowns nor celluloid crown forms are made specifically for mandibular incisors. Many options exist to repair carious primary incisors, but there is insufficient controlled, clinical data to suggest that one type of restoration is superior to another. This does not discount the fact that dentists have been using many of these crowns for years with much success. Operator preferences, esthetic demands by parents, the child's behavior, and moisture and hemorrhage control are all variables which affect the decision and ultimate outcome of whatever restorative treatment is chosen.

  11. Primary gastrointestinal lymphoma

    PubMed Central

    Aledavood, Amir; Nasiri, Mohammad Reza Ghavam; Memar, Bahram; Shahidsales, Soodabeh; Raziee, Hamid Reza; Ghafarzadegan, Kamran; Mohtashami, Samira

    2012-01-01

    Background: Extranodal lymphoma may arise anywhere outside lymph nodes mostly in the gastrointestinal (GI) tract as non-Hodgkin's disease. We reviewed the clinicopathological features and treatment results of patients with primary GI lymphoma. Materials and Methods: A total number of 30 cases with primary GI lymphoma were included in this study. Patients referred to the Radiation Oncology Department of Omid Hospital (Mashhad, Iran) during a 5-year period (2006-11). Clinical, paraclinical, and radiological data was collected from medical records of the patients. Results: Out of the 30 patients with primary GI lymphoma in the study, 12 were female (40%) and 18 were male (60%) (male to female ratio: 3/2). B symptoms were present in 27 patients (90%). Antidiuretic hormone (LDH) levels were elevated in 9 patients (32.1%). The most common primary site was stomach in 14 cases (46.7%). Other common sites included small intestine and colon each in 8 patients (26.7%). All patients had histopathologically proven non-Hodgkin's lymphoma. The most common histologic subtype was diffuse large B-cell lymphoma (DLBL) in 16 patients (53.3%). In addition, 28 patients (93.3%) received chemotherapy with cyclophosphamide, vincristine, doxorubicin, prednisolone (CHOP regimen). The median course of chemotherapy was 6 cources. Moreover, 8 patients (26.7%) received radiotherapy with cobalt 60. The median follow-up time was 26 months. The overall 5-year survival rate was 53% and the median survival time was 60 months. Conclusion: Primary GI lymphoma is commonly seen in stomach and small intestine and mostly is DLBCL or mucosa-associated lymphoid tissue (MALT) lymphoma. PMID:23626617

  12. Naturopathy and the Primary Care Practice

    PubMed Central

    Fleming, Sara A.; Gutknecht, Nancy C.

    2010-01-01

    Synopsis Naturopathy is a distinct type of primary care medicine that blends age-old healing traditions with scientific advances and current research. It is guided by a unique set of principles that recognize the body's innate healing capacity, emphasize disease prevention, and encourage individual responsibility to obtain optimal health. Naturopathic treatment modalities include diet and clinical nutrition, behavioral change, hydrotherapy, homeopathy, botanical medicine, physical medicine, pharmaceuticals, and minor surgery. Naturopathic physicians (NDs) are trained as primary care physicians in four-year, accredited doctoral-level naturopathic medical schools. Currently, there are 15 U.S. states, 2 U.S. territories, and a number of provinces in Canada, Australia, and New Zealand that recognize licensure for NDs. PMID:20189002

  13. Contemporary Management of Primary Distal Urethral Cancer.

    PubMed

    Traboulsi, Samer L; Witjes, Johannes Alfred; Kassouf, Wassim

    2016-11-01

    Primary urethral cancer is one of the rare urologic tumors. Distal urethral tumors are usually less advanced at diagnosis compared with proximal tumors and have a good prognosis if treated appropriately. Low-stage distal tumors can be managed successfully with a surgical approach in men or radiation therapy in women. There are no clear-cut indications for the choice of the most appropriate treatment modality. Organ-preserving modalities have shown effective and should be used whenever they do not compromise the oncological safety to decrease the physical and psychological trauma of dismemberment or loss of sexual/urinary function.

  14. Primary lumbar hernia: A rarely encountered hernia

    PubMed Central

    Sundaramurthy, Sharada; Suresh, H.B.; Anirudh, A.V.; Prakash Rozario, Anthony

    2015-01-01

    Introduction Lumbar hernia is an uncommon abdominal wall hernia, making its diagnosis and management a challenge to the treating surgeon. Presentation may be misleading and diagnosis often missed. An imaging study forms an indispensable aid in the diagnosis and surgery is the only treatment option. Presentation of case A 42 year old male presented with history of pain in lower back of 4 years duration and was being treated symptomatically over 4 years with analgesics and physiotherapy. He had noticed a swelling over the left side of his mid-back and consequently on examination was found to have a primary acquired lumbar hernia arising from the deep superior lumbar triangle of Grynfelt. Diagnosis was confirmed by Computed Tomographic imaging. Discussion A lumbar hernia may be primary or secondary with only about 300 cases of primary lumbar hernia reported in literature. Lumbar hernias manifest through two possible defects in the posterior abdominal wall, the superior being more common. Management remains surgical with various techniques emerging over the years. The patient at our center underwent an open sublay mesh repair with excellent outcome. Conclusion A surgeon may encounter a primary lumbar hernia perhaps once in his lifetime making it an interesting surgical challenge. Sound anatomical knowledge and adequate imaging are indispensable. Inspite of advances in minimally invasive surgery, it cannot be universally applied to patients with lumbar hernia and management requires a more tailored approach. PMID:26812667

  15. Fred Hoyle, primary nucleosynthesis and radioactivity

    NASA Astrophysics Data System (ADS)

    Clayton, Donald D.

    2008-10-01

    Primary nucleosynthesis is defined as that which occurs efficiently in stars born of only H and He. It is responsible not only for increasing the metallicity of the galaxy but also for the most abundant gamma-ray-line emitters. Astrophysicists have inappropriately cited early work in this regard. The heavily cited B2FH paper (Burbidge et al., 1957) did not effectively address primary nucleosynthesis whereas Hoyle (Hoyle, 1954) had done so quite thoroughly in his infrequently cited 1954 paper. Even B2FH with Hoyle as coauthor seems strangely to not have appreciated what Hoyle (Hoyle, 1954) had achieved. I speculate that Hoyle must not have thoroughly proofread the draft written in 1956 by E.M. and G.R. Burbidge. The clear roadmap of primary nucleosynthesis advanced in 1954 by Hoyle describes the synthesis yielding the most abundant of the radioactive isotopes for astronomy, although that aspect was unrealized at the time. Secondary nucleosynthesis has also produced many observable radioactive nuclei, including the first gamma-ray-line emitter to be discovered in the galaxy and several others within stardust grains. Primary gamma-ray emitters would have been even more detectable in the early galaxy, when the birth rate of massive stars was greater; but secondary emitters, such as 26Al, would have been produced with smaller yield then owing to smaller abundance of seed nuclei from which to create them.

  16. Advanced Climate Analysis and Long Range Forecasting

    DTIC Science & Technology

    2014-09-30

    1 DISTRIBUTION STATEMENT A. Approved for public release; distribution is unlimited. Advanced Climate Analysis and Long Range Forecasting...project is to improve the long range and climate support provided by the U.S. Naval Oceanography Enterprise (NOe) for planning, conducting, and...months, several seasons, several years). The primary transition focus is on improving the long range and climate support capabilities of the Fleet

  17. Disassembling and reintegration of large telescope primary mirror

    NASA Astrophysics Data System (ADS)

    Xu, Qi-rui; Fan, Bin; Zhang, Ming

    2014-09-01

    The success of the large telescope is largely linked to the excellent performance and reliability of the primary mirror. In order to maintain the quality of its reflective surface at the high expectations of astronomers, the primary mirror after almost two or three years of astronomical observations, needs to be removed and reinstalled for its cleaning and re-coating operation. There are a series of procedures such as the primary mirror cell dissembling from telescope, mirror handling, transportation, reintegration, alignment and so on. This paper will describe the experiences of disassembling and reintegration of large telescope primary mirror, taking a two meter grade primary mirror for example. As with all advanced and complex opto-mechanical systems, there has been the usual problems and trouble shooting.

  18. Transforming Coverage of Primary Prevention in Abnormal Psychology Courses.

    ERIC Educational Resources Information Center

    Dalton, James H.; And Others

    1994-01-01

    Maintains that a comprehensive understanding of abnormal psychology requires coverage of recent advances in primary prevention. Describes a conceptual scheme and recommends resources and teaching methods for instructors. Asserts that clinical and community psychology are conceptually distinct but complementary fields. (CFR)

  19. Bilingual Children with Primary Language Impairment: 3 Months after Treatment

    ERIC Educational Resources Information Center

    Pham, Giang; Ebert, Kerry Danahy; Kohnert, Kathryn

    2015-01-01

    Background: Evidence on the treatment effectiveness for bilingual children with primary language impairment (PLI) is needed to advance both theory and clinical practice. Of key interest is whether treatment effects are maintained following the completion of short-term intense treatments. Aims: To investigate change in select language and cognitive…

  20. Local Area Networks: Are There Advantages for Primary Schools?

    ERIC Educational Resources Information Center

    Aherran, Anne

    1986-01-01

    Examines the relative merits of using computer networks (several computers linked together and sharing a single disk drive) and stand-alone systems (self-contained units operating independently) in Australian primary school classrooms. Advances several arguments favoring stand-alone systems, which improve accessibility and enhance individual…

  1. Steroid estrogens in primary and tertiary wastewater treatment plants.

    PubMed

    Braga, O; Smythe, G A; Schafer, A I; Feitz, A J

    2005-01-01

    The concentrations of two natural estrogens (estrone (E1) and Estradiol (E2)) and one synthetic progestin (Ethinylestradiol (EE2)) were measured for different unit operations in an advanced sewage treatment plant and in a large coastal enhanced primary sewage treatment plant. The average influent concentration to both plants was similar: 55 and 53 ng/L for E1 and 22 and 12 ng/L for E2 for the advanced and enhanced primary STPs, respectively. The activated sludge process at the advanced STP removed up to 85% and 96% of E1 and E2, respectively. The enhanced primary sewage treatment plant was mostly ineffective at removing the steroids with only 14% of E1 and 5% of E2 being removed during the treatment process. EE2 was not been detected during the study period in the influent or effluent of either STP. The difference in the observed removal between the two plants is primarily linked to plant performance but the extent to which removal of steroid estrogens is due to bacterial metabolism (i.e. the advanced STP) rather than adsorption to the bacterial biomass remains unclear. The poor removal observed for the coastal enhanced primary STP may have implications for the receiving environment in terms of a greater potential for abnormal reproductive systems in marine animals, particularly if discharges are into large bays or harbours where flushing is limited.

  2. Doing More in Pediatric Primary Care: The Healthy Steps Model

    ERIC Educational Resources Information Center

    Kaplan-Sanoff, Margot

    2007-01-01

    Pediatric primary care provides an enormous window of opportunity to offer families information a