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Sample records for advanced primary open-angle

  1. [Surgery in the treatment of primary advanced open-angle glaucoma].

    PubMed

    Chiseliţă, D; Vancea, P P

    1995-01-01

    A series of 25 cases of advanced open-angle primitive glaucoma (C/D higher than 0.8, visual field stages C, D, E according to Greve's classification), operated upon by extended and adapted trabeculectomy, surgery being the initial step in the treatment of this affection, was reviewed. After a 18.5-month follow up, the progression of glaucoma was arrested in 60% of the cases, and a regression of papilloperimetric alterations was found in 8% of the cases. There was a significant correlation between the obtained IOP level and glaucoma course (in the cases with a favourable course postoperative IOP was of 15.5 mmHg, while in those evolving unfavorably IOP was of 18 mmHg). Our experience suggests that antiglaucoma surgery may be recommended as an initial treatment in those patients in whom a short-term drug trial (topic administration of 3 drugs for few days) induces a lowering of IOP to less than 15.5 mmHg, and life expectancy is not short. PMID:7766591

  2. Selective laser trabeculoplasty in treating post-trabeculectomy advanced primary open-angle glaucoma

    PubMed Central

    ZHANG, HONGYANG; YANG, YANGFAN; XU, JIANGANG; YU, MINBIN

    2016-01-01

    The aim of this study was to investigate the safety and efficacy of selective laser trabeculoplasty (SLT) treatment of patients with primary open-angle glaucoma (POAG) who could not obtain target intraocular pressure (IOP) through post-trabeculectomy medication. Sixteen patients with POAG (18 eyes), who could not obtain target IOP following medication and surgery, were treated with 360° SLT. The IOP, anterior chamber inflammation, and daytime and long-term IOP fluctuations before and 2 h, 1 day, 7 days, 1 month, 3 months, 6 months and 9 months after SLT were documented. SLT treatment success was defined as >20% IOP reduction compared with the baseline IOP at 6 and 9 months after the laser treatment date. Prior to SLT, the patients were administered different types (average, 2.8±0.8) of anti-glaucoma drugs and had an average IOP of 21.3±3.4 mmHg. Following SLT, the average IOP decreased to 16.2±3.0 mmHg and the success rate was 77.7%. The pre-SLT daytime IOP fluctuation was 4.1±1.4 mmHg, which decreased to 2.6±1.1 mmHg following the laser treatment (P<0.05). In conclusion, this study demonstrated that SLT could reduce the IOP in post-trabeculectomy patients with POAG, and reduce the daytime IOP fluctuations. PMID:26998042

  3. 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.

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

    PubMed Central

    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. PMID:26496696

  5. 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

  6. Metabolome-Wide Association Study of Primary Open Angle Glaucoma

    PubMed Central

    Burgess, L. Goodwin; Uppal, Karan; Walker, Douglas I.; Roberson, Rachel M.; Tran, ViLinh; Parks, Megan B.; Wade, Emily A.; May, Alexandra T.; Umfress, Allison C.; Jarrell, Kelli L.; Stanley, Brooklyn O. C.; Kuchtey, John; Kuchtey, Rachel W.; Jones, Dean P.; Brantley, Milam A.

    2015-01-01

    Purpose To determine if primary open-angle glaucoma (POAG) patients can be differentiated from controls based on metabolic characteristics. Methods We used ultra-high resolution mass spectrometry with C18 liquid chromatography for metabolomic analysis on frozen plasma samples from 72 POAG patients and 72 controls. Metabolome-wide Spearman correlation was performed to select differentially expressed metabolites (DEM) correlated with POAG. We corrected P values for multiple testing using Benjamini and Hochberg false discovery rate (FDR). Hierarchical cluster analysis (HCA) was used to depict the relationship between participants and DEM. Differentially expressed metabolites were matched to the METLIN metabolomics database; both DEM and metabolites significantly correlating with DEM were analyzed using MetaboAnalyst to identify metabolic pathways altered in POAG. Results Of the 2440 m/z (mass/charge) features recovered after filtering, 41 differed between POAG cases and controls at FDR = 0.05. Hierarchical cluster analysis revealed these DEM to associate into eight clusters; three of these clusters contained the majority of the DEM and included palmitoylcarnitine, hydroxyergocalciferol, and high-resolution METLIN matches to sphingolipids, other vitamin D-related metabolites, and terpenes. MetaboAnalyst also indicated likely alteration in steroid biosynthesis pathways. Conclusions Global ultrahigh resolution metabolomics emphasized the importance of altered lipid metabolism in POAG. The results suggest specific metabolic processes, such as those involving palmitoylcarnitine, sphingolipids, vitamin D-related compounds, and steroid precursors, may contribute to POAG status and merit more detailed study with targeted methods. PMID:26230767

  7. Ocular Decompression Retinopathy Following Canaloplasty for Primary Open Angle Glaucoma

    PubMed Central

    Li, Gai-yun; Alantaree, Samer; Wang, Jun-ming; Zhang, Hong

    2016-01-01

    Abstract Ocular decompression retinopathy (ODR), a rare postoperative complication following glaucoma surgery, is characterized by the transient appearance of scattered retinal hemorrhages. Here, we present a unique case of ODR in a patient with primary open angle glaucoma who underwent canaloplasty. A 31-year-old male patient presented with an intraocular pressure (IOP) of 60 mm Hg in the right eye. The IOP remained over 40 mm Hg, even when treated with maximum tolerated antiglaucoma medication. Canaloplasty drastically lowered IOP in the right eye from 40 to 7 mm Hg. However, fundus examination revealed ODR after surgery. The patient was treated with tobramycin and dexamethasone. Three months after canaloplasty, IOP remained in control at 16 mm Hg and all retinal hemorrhages had completely resolved. This case demonstrates that ODR can occur following canaloplasty and physicians should be aware of this potential complication in patients with severely elevated IOP. Sufficiently lowering IOP before surgery and gradually decreasing IOP during surgery may prevent ODR from occurring. PMID:26945386

  8. 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

  9. Epidemiological Properties of Primary Open Angle Glaucoma in Nigeria

    PubMed Central

    Abdu, Lawan

    2013-01-01

    Background. Primary open angle glaucoma (POAG) is progressive chronic optic neuropathy in adults in which intraocular pressure (IOP) and other currently unknown factors contribute to damage. POAG is the second commonest cause of avoidable blindness in Nigeria. Pattern of Presentation. POAG is characterized by late presentation. Absence of pain which is a driving force for seeking medical help, inadequacy of trained eye care personnel, paucity of facilities, misdistribution of resources, lack of awareness, poor education, and poverty may all contribute to this. Medical and surgical treatment options available are challenging and tasking. Screening for Glaucoma. Screening is the presumptive identification of unrecognized disease (POAG) by applying test(s) which can be applied rapidly. Such test(s) should be of high reliability, validity, yield, acceptable, and cost effective. The test should ideally be sensitive, specific, and efficient. It is difficult to select a suitable test that meets these criteria. Intraocular pressure (IOP) appears to be the easiest option. But, high IOP is not diagnostic nor does normal value exclude the disease. Health education is a possible strategy in early case detection and management. Treatment of POAG. Glaucoma treatment can either be medical or surgical (this includes laser). Considering unavailability, potency, cost, and long-term effects of medication, surgery (trabeculectomy) could be a better option. Laser trabeculoplasty is available in a few centers. Viscocanalostomy is not routinely performed. Patient education is vital to success as management is for life. Conclusion. POAG remains a cause of avoidable blindness in Nigeria. There is need for long-term strategy to identify patients early and institute prompt management. Improvement in training of eye care personnel and provision of up to date equipment is essential in achieving this goal. PMID:23762529

  10. Glycans of the trabecular meshwork in primary open angle glaucoma.

    PubMed Central

    Chapman, S A; Bonshek, R E; Stoddart, R W; O'Donoghue, E; Goodall, K; McLeod, D

    1996-01-01

    AIMS: Glycan expression was compared in glaucomatous trabecular meshwork (TM) and normal TM in order to determine any differences which may reflect pathological changes underlying primary open angle glaucoma (POAG). METHODS: Resin embedded TM from trabeculectomy specimens from 15 eyes with POAG and from 12 eyes with normal anterior segments were probed with a panel of biotinylated lectins and an avidin-peroxidase revealing system at the light microscope level. Statistical analyses were performed on the comparative staining results. RESULTS: The lectins ConA and ePHA showed strong staining in all areas of both glaucomatous and normal TM; ePHA staining of Schlemm's canal (SC) from POAG TM was significantly less than that from normal TM (ePHA-SC p = 0.04). The lectins PSA, LCA, and SNA bound moderately strongly to SC endothelium and weakly to the endothelium of the corneoscleral meshwork (CSM); glaucomatous SC endothelial binding was significantly less than that of normal SC endothelium for PSA and LCA (PSA-SC p = 0.002, LCA-SC p = 0.002). STA and DSA showed moderately strong binding while WGA, ECA, AHA, and MPA bound weakly throughout the TM; for DSA and MPA this staining was significantly greater in POAG than in normal TM (DSA-SC p = 0.001, DSA-CSM p = 0.002, MPA-SC p = 0.01, MPA-CSM p = 0.02). Jac stained strongly throughout the TM and showed no significant difference in POAG compared with normal TM (Jac-SC p = 0.6, Jac-CSM p = 1). 1PHA, SBA, DBA, CTA, UEA-1 and LTA did not bind to glaucomatous TM or normal TM. There were no age-related changes seen. CONCLUSIONS: The expression of some complex and hybrid, bisected and non-bisected N-linked glycans is significantly diminished in glaucomatous TM compared with normal TM. Some glycans with multiple N-acetylglucosamine residues and O-linked glycans with terminal and subterminal galactosyl groups are significantly increased in POAG TM. Glycan expression does not change significantly with age in POAG or normal TM. Images

  11. 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.

  12. Selective Laser Trabeculoplasty as Primary Treatment for Open-Angle Glaucoma.

    PubMed

    Kadasi, Laith M; Wagdi, Safa; Miller, Kimberly V

    2016-01-01

    Open-angle glaucoma is a silent, chronic disorder which results in progressive and permanent vision loss. Designing the optimal treatment regimen can be particularly challenging in the management of high-risk patients with frequent loss to follow-up or a longstanding history of medication noncompliance. In this article we aim to review fundamental techniques in glaucoma diagnosis and treatment with emphasis on the strengths and weaknesses of selective laser trabeculoplasty, a technique in modern therapy which may mold the future of primary treatment in open angle glaucoma management. [Full article available at http://rimed.org/rimedicaljournal-2016-06.asp, free with no login]. PMID:27247968

  13. Combination medical treatment for primary open angle glaucoma and ocular hypertension: a network meta-analysis

    PubMed Central

    Michelessi, Manuele; Lindsley, Kristina; Yu, Tsung; Li, Tianjing

    2014-01-01

    This is the protocol for a review and there is no abstract. The objectives are as follows: The objectives of this review are to examine the comparative effectiveness and safety of different glaucoma fixed combination therapies and monotherapies in eyes with primary open angle glaucoma or ocular hypertension and to provide relative rankings of these treatments. PMID:25774087

  14. 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

  15. [Iris examination in transformed light in primary open-angle glaucoma].

    PubMed

    Vodovozov, A M; Rybnikov, A A

    1991-01-01

    The iris was examined in transformed light by iridochromoscopy, iridochromophotography, biomicroscopy in polarized light, transillumination in red light, and fluorescent iridoangiography in 83 eyes of patients with primary open-angle glaucoma and 117 eyes of normal reference subjects. The examinations have shown the prevalence of trophic and vascular shifts in the iris of all glaucoma patients as against the reference patients (R 0.05). The major iris changes revealed in primary open-angle glaucoma were stromal atrophy with the predominant involvement of the pupil segment, destruction of the pupil pigmented border, exogenic pigmentation of the pupil and ciliary segments, thickening of the anterior border layer, pseudoexfoliation of the pupil edge, defects of the posterior pigmented lamina disseminated in the pupil segment, hypoperfusion of the iris vessels combined with their impaired permeability and micro-neovascularization in the iris edge and ciliary agea. PMID:2035203

  16. [NEW SURGICAL APPROACH IN PRIMARY OPEN-ANGLE GLAUCOMA: XEN GEL STENT A MINIMALLY INVASIVE TECHNIQUE].

    PubMed

    Dupont, G; Collignon, N

    2016-02-01

    Primary open-angle glaucoma is a progressive ocular disease affecting adults and associated with visual field defect. The aim of its treatment is to lower the ocular pressure by means of ocular drops, laser or surgery. To date, traditional surgical techniques still remain quite invasive, but recent research efforts have been made with a view to develop minimally invasive techniques. The Xen Gel Stent is one of them. It allows a safe and efficient lowering of ocular pressure by creating a sub-conjunctival flow, following an ab interno procedure that highly preserves the architecture of the treated eye. PMID:27141652

  17. Macular microvasculature alterations in patients with primary open-angle glaucoma: A cross-sectional study.

    PubMed

    Xu, Huan; Yu, Jian; Kong, Xiangmei; Sun, Xinghuai; Jiang, Chunhui

    2016-08-01

    To evaluate and compare macular microvasculature changes in eyes with primary open-angle glaucoma (POAG) to normal eyes, and to assess associations among the retinal microvasculature, neural structural damage, and visual field loss.Ninety-nine eyes (68 patients with POAG and 31 normal subjects) were enrolled in this study. Thirty-five eyes with early-stage glaucoma (EG), 33 eyes with advanced-stage glaucoma (AG), and 31 normal eyes were included. An optical coherence tomography system with a split-spectrum amplitude-decorrelation angiography algorithm was used to measure the macular capillary vessel area density and retinal thickness. Visual field testing (30-2 and 10-2 programs) was performed using a Humphrey field analyzer. Correlations between the capillary vessel area density, retinal thickness, and visual field parameters were analyzed.Compared to normal eyes, those with EG and AG had a lower macular capillary vessel area density and lesser retinal thickness (P < 0.001, all). Results of multivariate linear regression analyses showed that each standard deviation (SD) decrease in the vessel area density was associated with a 1.5% and 4.2% thinning of the full retinal thickness and inner retinal layer thickness, respectively. Each SD decrease in the vessel area density was also associated with a 12.9% decrease in the mean sensitivity and a 33.6% increase in the pattern standard deviation (P < 0.001, both). The Pearson partial regression analysis model showed that the vessel area density was most strongly associated with the inner retinal layer thickness and inferior hemimacular thickness. Furthermore, a lower vessel area density was strongly associated with a more severe hemimacular visual field defect and the corresponding hemimacular retinal thickness.The macular capillary vessel area density and retinal thickness were significantly lower in eyes with POAG than in normal eyes. A diminished macular microvasculature network is closely associated with

  18. Clinical Assessment of Lamina Cribrosa Curvature in Eyes with Primary Open-Angle Glaucoma

    PubMed Central

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

    2016-01-01

    Purpose Quantitative evaluation of lamina cribrosa (LC) posterior bowing in primary open-angle glaucoma (POAG) eyes using swept-source optical coherence tomography. Methods Patients with POAG (n = 123 eyes) and healthy individuals of a similar age (n = 92 eyes) were prospectively recruited. Anterior laminar insertion depth (ALID) was defined as the vertical distance between the anterior laminar insertion and a reference plane connecting the Bruch’s membrane openings (BMO). The mean LC depth (mLCD) was approximated by dividing the area enclosed by the anterior LC, the BMO reference plane, and the two vertical lines for ALID measurement by the length between those two vertical lines. The LC curvature index was defined as the difference between the mLCD and the ALID. The factors influencing the LC curvature index were evaluated. Results The ALID and mLCD were significantly larger in POAG eyes than in healthy controls (P < 0.05). The LC curvature index was significantly larger in POAG eyes than in healthy controls on both the horizontal (85.8 ± 34.1 vs. 68.2 ± 32.3 μm) and vertical meridians (49.8 ± 38.5 vs. 32.2 ± 31.1 μm, all P < 0.001). Multivariate regression showed significant associations of greater disc area (P < 0.001), vertical C/D ratio (P < 0.001) and mLCD (P < 0.001), smaller rim area (P = 0.001), thinner average RNFLT (P < 0.001), and myopic refraction (P = 0.049) with increased LC curvature index. There was no difference in the LC curvature index between mild (MD > –6 dB) and moderate-to-advanced glaucoma (MD < –6 dB, P = 0.95). Conclusions LC posterior bowing was increased in POAG eyes, and was significantly associated with structural optic nerve head (ONH) changes but not with functional glaucoma severity. Quantitative evaluation of LC curvature can facilitate assessment of glaucomatous ONH change. PMID:26963816

  19. 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.

  20. 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. PMID:25861811

  1. 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

  2. [The use of biologically controlled ultrasound therapy for the combined treatment of primary open-angle glaucoma].

    PubMed

    Novikova, E G; Baranov, V I

    2010-01-01

    The present study included 160 patients (206 eyes) presenting with the initial and advanced stages of primary open-angle glaucoma. 120 patients (157 eyes) were treated using biologically controlled ultrasound therapy besides traditional medicamentous therapy, the remaining 40 ones (49 eyes) were given only conventional medication. Results of the treatment were evaluated based on a set of commonly used hydrodynamic and electrophysiological characteristics of the quality of visual function. Biologically controlled massage of trabecular structures of the affected eyes made it possible to stabilize and improve major hydrodynamic characteristics of the eyeball drainage system, visual function, and electrophysiological parameters. Biologically controlled ultrasound therapy proved to produce a more pronounced beneficial effect on ocular hydrodynamics than the traditional ultrasonic treatment. The positive action of biologically controlled therapy persisted during 8 months; its repeated sessions prolonged this period up to 2 years. PMID:21328903

  3. 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

  4. 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

  5. Ocular Decompression Retinopathy Following Canaloplasty for Primary Open Angle Glaucoma: A Case Report.

    PubMed

    Li, Gai-Yun; Alantaree, Samer; Wang, Jun-Ming; Zhang, Hong

    2016-03-01

    Ocular decompression retinopathy (ODR), a rare postoperative complication following glaucoma surgery, is characterized by the transient appearance of scattered retinal hemorrhages.Here, we present a unique case of ODR in a patient with primary open angle glaucoma who underwent canaloplasty. A 31-year-old male patient presented with an intraocular pressure (IOP) of 60 mm Hg in the right eye. The IOP remained over 40 mm Hg, even when treated with maximum tolerated antiglaucoma medication. Canaloplasty drastically lowered IOP in the right eye from 40 to 7 mm Hg. However, fundus examination revealed ODR after surgery. The patient was treated with tobramycin and dexamethasone. Three months after canaloplasty, IOP remained in control at 16 mm Hg and all retinal hemorrhages had completely resolved.This case demonstrates that ODR can occur following canaloplasty and physicians should be aware of this potential complication in patients with severely elevated IOP. Sufficiently lowering IOP before surgery and gradually decreasing IOP during surgery may prevent ODR from occurring. PMID:26945386

  6. 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

    2016-01-01

    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 (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. PMID:27241461

  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. 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

  9. Structural brain alterations in primary open angle glaucoma: a 3T MRI study

    PubMed Central

    Wang, Jieqiong; Li, Ting; Sabel, Bernhard A.; Chen, Zhiqiang; Wen, Hongwei; Li, Jianhong; Xie, Xiaobin; Yang, Diya; Chen, Weiwei; Wang, Ningli; Xian, Junfang; He, Huiguang

    2016-01-01

    Glaucoma is not only an eye disease but is also associated with degeneration of brain structures. We now investigated the pattern of visual and non-visual brain structural changes in 25 primary open angle glaucoma (POAG) patients and 25 age-gender-matched normal controls using T1-weighted imaging. MRI images were subjected to volume-based analysis (VBA) and surface-based analysis (SBA) in the whole brain as well as ROI-based analysis of the lateral geniculate nucleus (LGN), visual cortex (V1/2), amygdala and hippocampus. While VBA showed no significant differences in the gray matter volumes of patients, SBA revealed significantly reduced cortical thickness in the right frontal pole and ROI-based analysis volume shrinkage in LGN bilaterally, right V1 and left amygdala. Structural abnormalities were correlated with clinical parameters in a subset of the patients revealing that the left LGN volume was negatively correlated with bilateral cup-to-disk ratio (CDR), the right LGN volume was positively correlated with the mean deviation of the right visual hemifield, and the right V1 cortical thickness was negatively correlated with the right CDR in glaucoma. These results demonstrate that POAG affects both vision-related structures and non-visual cortical regions. Moreover, alterations of the brain visual structures reflect the clinical severity of glaucoma. PMID:26743811

  10. An Updated Review on the Genetics of Primary Open Angle Glaucoma

    PubMed Central

    Abu-Amero, Khaled; Kondkar, Altaf A.; Chalam, Kakarla V.

    2015-01-01

    Epidemiological studies suggest that by 2020 the prevalence of primary open angle glaucoma (POAG) is estimated to increase to 76.0 million, and to 111.8 million by 2040 globally due to the population aging. The prevalence of POAG is the highest among those of African descent, followed by Asians, and the lowest in Europeans. POAG is a genetically complex trait with a substantial fraction exhibiting a significant heritability. Less than 10% of POAG cases in the general population are caused by specific gene mutations and the remaining cases are polygenic. Quantitative traits related to POAG pathogenesis such as intra-ocular pressure (IOP), vertical cup/disc ratio (VCDR), optic disc area, and central corneal thickness (CCT) are highly heritable, and likely to be influenced at least in part by genes and show substantial variation in human populations. Recent genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs) at different loci including CAV1/CAV2, TMCO1, CDKN2B-AS1, CDC7-TGFBR3, SIX1/SIX6, GAS7 and ATOH7 to be associated with POAG and its related quantitative traits (endophenotypes). The chapter provides a brief overview on the different GWAS and SNP association studies and their correlation with various clinical parameters important for POAG in the population worldwide, including the Middle East. PMID:26690118

  11. Elevated Transforming Growth Factor β1 in Plasma of Primary Open-Angle Glaucoma Patients

    PubMed Central

    Kuchtey, John; Kunkel, Jessica; Burgess, L. Goodwin; Parks, Megan B.; Brantley, Milam A.; Kuchtey, Rachel W.

    2014-01-01

    Purpose. To test the hypothesis that primary open-angle glaucoma (POAG) patients have a systemic elevation of transforming growth factor β1 (TGFβ1). Methods. Plasma was prepared from blood samples drawn from patients of the Vanderbilt Eye Institute during clinic visits. Concentrations of total TGFβ1 and thrombospondin-1 (TSP1) in plasma were determined by ELISA. Statistical significance of differences between POAG and control samples was evaluated by Mann-Whitney test. Regression analysis was used to evaluate correlations between plasma TGFβ1 and patient age and between plasma TGFβ1 and TSP1. Results. Plasma samples were obtained from 148 POAG patients and 150 controls. Concentration of total TGFβ1 in the plasma of POAG patients (median = 3.25 ng/mL) was significantly higher (P < 0.0001) than in controls (median = 2.46 ng/mL). Plasma TGFβ1 was not correlated with age of patient (P = 0.17). Thrombospondin-1 concentration was also significantly higher (P < 0.0001) in POAG patients (median = 0.774 μg/mL) as compared to controls (median = 0.567 μg/mL). Plasma total TGFβ1 and TSP1 concentrations were linearly correlated (P < 0.0001). Conclusions. Plasma samples from POAG patients display elevated total TGFβ1 compared to controls, consistent with elevated systemic TGFβ1 in POAG patients. PMID:25061114

  12. Comparison of selective laser trabeculoplasty (SLT) in primary open angle glaucoma and pseudoexfoliation glaucoma

    PubMed Central

    Ayala, Marcelo; Chen, Enping

    2011-01-01

    Background and objective The aim of the present study was to compare intraocular pressure (IOP) reduction and inflammation after selective laser trabeculoplasty (SLT) treatment in patients suffering from primary open angle (POAG) vs pseudoexfoliative (PXFG) glaucoma. Study design/patients and methods Sixty patients (60 eyes) participated in the study. Glaucoma patients (POAG or PXFG) scheduled for treatment with SLT were included. Inflammation was measured with a laser flare meter (Kowa FM-500). Measurements were made before SLT and 2 hours, 1 week, and 1 month after SLT treatment. IOP was also checked at the same time intervals. Results Inflammation after SLT showed no significant difference between the groups (t-test, before: P = 0.16; 2 hours: P = 0.14; 1 week: P = 0.12; and 1 month: P = 0.36). IOP reduction was the same in both groups (t-test, P = 0.27). Conclusion SLT safely reduces IOP in both POAG and PXFG. Pseudoexfoliation does not seem to be a risk factor for post-laser complications. PMID:22069348

  13. Elevated urine formaldehyde in elderly patients with primary open angle glaucoma

    PubMed Central

    Cui, Ying; Su, Tao; Zhang, Shao-Dan; Huang, Ping; He, Ying-Ge; Liu, Ying; Zhang, Chun; Ritch, Robert; He, Rong-Qiao

    2016-01-01

    AIM To investigate the risk factor of primary open angle glaucoma (POAG), which is the leading cause of irreversible blindness worldwide. An abnormally high level of endogenous formaldehyde (FA) has recently been found correlated with cell death and neurodegenerative disease, raising the possibility of a putative correlation of abnormal endogenous FA with POAG. METHODS Thirty-four elderly patients with POAG and sixteen healthy controls were enrolled. Glaucomatous visual defects were present at both the functional (visual field) and structural [retinal nerve fiber layer (RNFL) thickness] levels. Morning urine samples were obtained and were analyzed by high-performance liquid chromatography (HPLC) to detect the endogenous FA level in a double blind manner. RESULTS Patients with POAG (P<0.05) had significantly higher urine FA levels. The urine FA level of patients with severe visual field defects [mean deviation (MD)≥12 dB] was significantly (P<0.001) greater than that of patients with mild to moderate defects (MD<12 dB). By optical coherence tomography (OCT), the superior and inferior RNFL thickness of POAG group was significantly (P<0.001) thinner than in controls. Furthermore, the superior and inferior thinning of the RNFL was correlated with the elevation of urine FA concentration. CONCLUSION Endogenous FA level is positively correlated with the neuronal defects of POAG. PMID:27158612

  14. 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

  15. Extracting Primary Open-Angle Glaucoma from Electronic Medical Records for Genetic Association Studies

    PubMed Central

    Restrepo, Nicole A.; Farber-Eger, Eric; Goodloe, Robert; Haines, Jonathan L.; Crawford, Dana C.

    2015-01-01

    Electronic medical records (EMRs) are being widely implemented for use in genetic and genomic studies. As a phenotypic rich resource, EMRs provide researchers with the opportunity to identify disease cohorts and perform genotype-phenotype association studies. The Epidemiologic Architecture for Genes Linked to Environment (EAGLE) study, as part of the Population Architecture using Genomics and Epidemiology (PAGE) I study, has genotyped more than 15,000 individuals of diverse genetic ancestry in BioVU, the Vanderbilt University Medical Center’s biorepository linked to a de-identified version of the EMR (EAGLE BioVU). Here we develop and deploy an algorithm utilizing data mining techniques to identify primary open-angle glaucoma (POAG) in African Americans from EAGLE BioVU for genetic association studies. The algorithm described here was designed using a combination of diagnostic codes, current procedural terminology billing codes, and free text searches to identify POAG status in situations where gold-standard digital photography cannot be accessed. The case algorithm identified 267 potential POAG subjects but underperformed after manual review with a positive predictive value of 51.6% and an accuracy of 76.3%. The control algorithm identified controls with a negative predictive value of 98.3%. Although the case algorithm requires more downstream manual review for use in large-scale studies, it provides a basis by which to extract a specific clinical subtype of glaucoma from EMRs in the absence of digital photographs. PMID:26061293

  16. [Effect of fundus image devices for early diagnosis of primary open angle glaucoma].

    PubMed

    Pan, Ying-zi

    2009-10-01

    Evaluation of the optic disc and retinal nerve fiber layer measurements (RNFL) with stereophotography is the current "gold standard" for the diagnosis of early primary open angle glaucoma (POAG), but it is still subjective and is dependent too much upon an experienced observer. Substantial variability exists in the interpretation of optic disc change over time. There are consistent evidences that image analysis devices such as optical coherence tomography (OCT) and Heidelberg retina tomograph (HRT-II) can detect early to moderate glaucoma as well as expert assessment of stereoscopic optic disc and RNFL photographs. Optic disc and RNFL defect can be quantitatively measured by these devices. But the sensitivity and specificity of the measurements obtained with these devices are not good enough for the early diagnosis of POAG at this time due to several reasons, such as individual variety of the structure parameters in normal subjects, lack of powerful normative database, lack of diagnostic parameters which are good enough both in sensitivity and specificity for detecting early glaucoma damage. However, information obtained from these image analysis devices might be helpful in early POAG diagnosis if clinicians can understand the advantages and limitations of these instruments. PMID:20137444

  17. Selective laser trabeculoplasty for primary open angle glaucoma: six-year follow up

    NASA Astrophysics Data System (ADS)

    Koev, Krassimir

    2005-04-01

    In order to establish the long-term efficacy of selective laser trabeculoplasty for primary open-angle glaucoma [POAG], trabecular meshwork of 34 eyes (21 patients) with POAG was treated with Q-switched frequency doubled Nd-YAG laser with wavelength of 532 nm Coherent Selecta 7000 (SLT). The eyes were divided in two groups: group 1-18 eyes with pigmentation degree in the frontal chamber angle of 1 and 2; group 2-16 eyes with pigmentation degree of 3 and 4. An average of 104 spots on 360 degrees was applied stepwise to the trabecular meshwork of every eye. The treatment and follow up period lasted 6 years. The mean prepoerative intraocular pressure [IOP] in group 1 was 25,5+/-1,5 mmHg, and in group 2-26+/-1 mmHg. During the last visit 6 years after SLT, the mean IOP in group 1 was 18,7+/-1.4 mmHg. Statistically significant decrease of IOP [p<0.001] was observed after SLT by an average of 6,8 mmHg [26.7%]. During the last visit 6 years after SLT in group 2, the mean IOP was 18.8+/-1.2 mmHg. Statistically significant IOP decrase method for POAG treatment and that IOP decrase in treated eyes is preserved for several years.

  18. Risk Factors for Primary Open Angle Glaucoma (POAG) Progression: A Study Ruled in Torino

    PubMed Central

    Actis, A.G.; Versino, E.; Brogliatti, B.; Rolle, T.

    2016-01-01

    Purpose: Aim of this retrospective, observational study is to describe features of a population sample, affected by primary open angle glaucoma (POAG) in order to evaluate damage progression on the basis of the emerged individual risk factors. Methods: We included 190 caucasian patients (377 eyes), evaluating relationship between individual risk factors (explicative variables) and MD (Mean Deviation) of standard automated perimetry. We also considered the dependent variable NFI (Neural Fiber Index) of GDx scanning laser polarimetry. Progression has been evaluated through a statistic General Linear Model on four follow up steps (mean follow up 79 months). Results: Factors reaching statistical significance, determining a worsening of the MD variable, are: age (P<0.0001), intraocular pressure (IOP) at follow up (P < 0.0001), female gender (P<0.0001), hypertension (P< 0.0001) and familiarity (P = 0.0006). Factors reaching statistical significance, determining a worsening of the NFI variable, are only IOP at follow up (P = 0.0159) and depression (P = 0.0104). Conclusion: Results of this study confirm and enforce data coming from most recent studies: IOP remains the main risk factor for glaucoma assess and progression; age and familiarity are great risk factors as underlined in the last decades; female sex can be an important risk factors as emerged only in the last years; arterial hypertension should always be evaluated in timing of our clinic follow up. PMID:27347249

  19. Progressive Thinning of Visual Cortex in Primary Open-Angle Glaucoma of Varying Severity

    PubMed Central

    Dai, Chao; Xie, Bing; Liang, Minglong; Zhao, Lu; Yin, Xuntao; Wang, Jian

    2015-01-01

    The aim of this study was to investigate possible changes of cortical thickness in the visual cortex in primary open-angle glaucoma (POAG) of varying severity. Twenty normal controls (NC), 20 mild (MP) and 17 severe (SP) POAG patients were recruited and scanned using magnetic resonance imaging. Cortical thickness analyses with regions of interest (V1, V2, ventral V3, V4 and V5/MT+) were used to assess the cortical changes among the three groups. Furthermore, the associations of cortical thickness with retinal nerve fiber layer (RNFL) thickness and mean deviation of visual field were analyzed. Compared with the NC group, decreased cortical thickness was detected in the bilateral V5/MT+ areas in the MP group and the left V1, bilateral V2 and V5/MT+ areas in the SP group. Cortical thinning of the bilateral V2 areas was detected in the SP group compared with the MP group. In addition, cortical thinning of these visual areas was related to the ophthalmologic measurements. In conclusion, POAG patients exhibit cortical thinning in the bilateral V5/MT+ in the early stage of disease. The cortical degeneration in visual areas is discrepant with disease progressing and the dorsal pathway might be selectively damaged in POAG. Therefore, the cortical thinning of these visual areas may play a key role in the progression of POAG and can serve as a novel biomarker for accurately evaluating the severity of POAG. PMID:25816070

  20. Evaluation of the significance of some diagnostic parameters in making an early diagnose of primary open-angle glaucoma

    PubMed Central

    Polaczek-Krupa, Barbara; Grabska-Liberek, Iwona

    2012-01-01

    Summary Background The aim of this study was to evaluate diagnostic parameters and analysis of their advantages and limitations in early diagnostics of primary open-angle glaucoma (POAG). Cup/disc ratio (C/D), nerve fiber index (NFI) and mean deviation of retinal sensitivity (MD) were considered. Material/Methods Fifty primary open-angle glaucoma patients (95 eyes), 67 primary open-angle glaucoma suspects (128 eyes), and 77 healthy subjects (148 eyes) underwent full ophthalmologic examination and also HRT, GDx and FDT examinations for determination of C/D, NFI, and MD parameters. Student’s t test was used to confirm the statistical significance of the differences between the particular group pairs. Histograms of distribution of the occurrence frequency of the parameter values in the groups were plotted. Results The mean values of C/D were 0.65±0.11, 0.58±0.11 and 0.43±0.11, NFI 37.0±22.7, 18.5±5.6 and 15.1±4.8 and MD −3.00±5.07, −077±2.49 and −0.29±1.94, respectively. Statistically significant differences between the particular groups were found. There was a partial overlapping of the histograms of distribution of the occurrence frequency of the parameter values. Conclusions The basic diagnostic C/D NFI and MD parameters in primary open-angle glaucoma patients, primary open-angle glaucoma suspects and healthy subjects differed significantly. These parameters are important diagnostic tools in glaucoma diagnosis. A limitation of their applicability is related to a high scatter of the results and their overlapping in particular groups. PMID:22739736

  1. 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

  2. Nailfold Capillary Abnormalities in Primary Open-Angle Glaucoma: A Multisite Study

    PubMed Central

    Pasquale, Louis R.; Hanyuda, Akiko; Ren, Ai; Giovingo, Michael; Greenstein, Scott H.; Cousins, Clara; Patrianakos, Thomas; Tanna, Angelo P.; Wanderling, Christopher; Norkett, William; Wiggs, Janey L.; Green, Kelsey; Kang, Jae H.; Knepper, Paul A.

    2015-01-01

    Purpose There is considerable evidence for systemic vascular dysfunction in primary open-angle glaucoma (POAG). We performed nailfold capillary video microscopy to observe directly the nature of nonocular microvasculature abnormalities in POAG. Methods We enrolled 199 POAG patients and 124 control subjects from four sites. We used JH-1004 capillaroscopes to perform nailfold capillary video microscopy on the fourth and fifth digits of each subject's nondominant hand. Videos were evaluated for hemorrhages, dilated capillary loops > 50 μm, and avascular zones > 100 μm by graders masked to case status. Multivariable odds ratios (ORs) and 95% confidence intervals (CIs) for POAG were obtained by means of logistic regression analyses that were applied to data from all cases and controls. Corresponding estimates of moderate or severe POAG versus mild POAG (based on the Hodapp-Anderson-Parrish scale) were obtained among cases only. Results After controlling for demographic factors, family history of glaucoma, systemic diseases, and use of anticoagulation and antiplatelet therapy, for each 100 nailfold capillaries assessed, all types of microvascular abnormalities were significantly associated with POAG. Specifically, the presence of any dilated capillaries (OR = 2.9; 95% CI, 1.6–5.6), avascular zones (OR = 4.4; 95% CI, 1.7–11.3) and hemorrhages (OR = 12.2; 95% CI, 5.9–25.1) were associated with POAG. Among cases, the frequency of microvascular abnormalities was not associated with glaucoma severity (P ≥ 0.43). Conclusions These data provided support for nonocular capillary bed abnormalities in POAG. Comparable vascular abnormalities in the optic nerve may render it susceptible to glaucomatous damage. PMID:26523386

  3. Intraocular pressure after phacoemulsification in patients with uncontrolled primary open angle glaucoma

    PubMed Central

    Iancu, R; Corbu, C

    2014-01-01

    Abstract Rationale (hypothesis). Although cataract and glaucoma represent an increasingly common situation encountered concomitantly, the management of this association is still debatable. Objective (aim). We aimed to assess intraocular pressure dynamics after phacoemulsification in patients with uncontrolled primary open angle glaucoma (POAG). Methods and Results. The present study was designed as a prospective, non-randomized, cohort study. The study population comprised of 38 patients with medically uncontrolled POAG who underwent cataract surgery by phacoemulsification between 2011 and 2012. Most of the patients (32/38, 84.2%) needed glaucoma surgery after a variable time (mean time between surgeries was 11.6 +/- 4.18 months). Mean preoperative IOP decreased with 2,1 +/- 3,7 mmHg at 6 months (CI 95% 1.96 to 3.56) and with 1,9 +/- 3,9 mmHg at 12 months compared with the baseline IOP. Postoperative IOP was statistically significant lower compared with its preoperative value at 6 months (p=9.11 x 10⁻⁸) and at one year (p=9.2 x 10⁻⁵). The difference between mean IOP at 6 months and 1 year after cataract surgery was not statistically significant (p>0.05). Preoperatively, all the patients received topical antiglaucoma therapy. After phacoemulsification, their number did not change statistically significant, but it showed a slight increase. Average number of topical glaucoma medications used preoperatively was 2.66 + / -0.66, while at 6 months after surgery it was 2.71 + / - 0,75 and at 12 months postoperatively, 2.9 +/- 0.53. Discussion. IOP decreased statistically significant after phacoemulsification in patients with uncontrolled POAG, but the decrease was not sufficient for optimal glaucoma management; therefore, many patients needed subsequent glaucoma surgery. PMID:24653751

  4. 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

  5. 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

  6. Axial Myopia Is Associated with Visual Field Prognosis of Primary Open-Angle Glaucoma

    PubMed Central

    Qiu, Chen; Qian, Shaohong; Sun, Xinghuai; Zhou, Chuandi; Meng, Fanrong

    2015-01-01

    Purpose To identify whether myopia was associated with the visual field (VF) progression of primary open-angle glaucoma (POAG). Methods A total of 270 eyes of 270 POAG followed up for more than 3 years with ≥9 reliable VFs by Octopus perimetry were retrospectively reviewed. Myopia was divided into: mild myopia (-2.99 diopter [D], 0), moderate myopia (-5.99, 3.00 D), marked myopia (-9.00, -6.00 D) and non-myopia (0 D or more). An annual change in the mean defect (MD) slope >0.22 dB/y and 0.30 dB/y was defined as fast progression, respectively. Logistic regression was performed to determine prognostic factors for VF progression. Results For the cutoff threshold at 0.22 dB/y, logistic regression showed that vertical cup-to-disk ratio (VCDR; p = 0.004) and the extent of myopia (p = 0.002) were statistically significant. When logistic regression was repeated after excluding the extent of myopia, axial length (AL; p = 0.008, odds ratio [OR] = 0.796) reached significance, as did VCDR (p = 0.001). Compared to eyes with AL≤23 mm, the OR values were 0.334 (p = 0.059), 0.309 (p = 0.044), 0.266 (p = 0.019), 0.260 (p = 0.018), respectively, for 23 26 mm. The significance of vertical cup-to-disk ratio of (p = 0.004) and the extent of myopia (p = 0.008) did not change for the cutoff threshold at 0.30dB/y. Conclusions VCDR and myopia were associated with VF prognosis of POAG. Axial myopia may be a protective factor against VF progression. PMID:26214313

  7. 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

  8. Anterior Lamina Cribrosa Insertion in Primary Open-Angle Glaucoma Patients and Healthy Subjects

    PubMed Central

    Lee, Kyoung Min; Kim, Tae-Woo; Weinreb, Robert N.; Lee, Eun Ji; Girard, Michaël J. A.; Mari, Jean Martial

    2014-01-01

    Purpose To determine using swept-source optical coherence tomography (SS-OCT) whether there are differences in the location of the anterior lamina cribrosa insertion (ALI) in primary open-angle glaucoma (POAG) patients and healthy subjects. Methods Fifty three eyes from 53 patients with POAG, and 53 eyes from 53 age-matched healthy subjects were included prospectively in Seoul National University Bundang Hospital. Twelve radial line B-scans centered on the optic disc in every half-clock-hour meridian were acquired using SS-OCT. The ALI position was assessed by measuring two parameters: (1) ALI distance (ALID)—the distance from the anterior scleral canal opening (ASCO) to the ALI; and (2) marginal anterior lamina cribrosa surface depth (mALCSD)—the perpendicular distance from the ASCO plane to the anterior lamina cribrosa surface. These parameters were compared between the two groups for each meridian. Results Both ALID (256±54 vs. 209±37 µm, mean ± SD, p<0.001) and mALCSD (232±63 vs. 187±40 µm, p<0.001) were significantly greater in the POAG group than in the normal group. The largest difference was observed at the 6.5 o′clock and 11.5 o′clock meridians for both ALID and mALCSD. Multiple regression analysis revealed a negative correlation between age and both ALID and mALCSD in the control group, and a negative correlation between mean deviation of the visual field test and both ALID and mALCSD in the POAG group. Conclusions The ALI was displaced posteriorly in eyes with POAG compared to those of healthy controls. This finding suggests that the posteriorly located lamina cribrosa insertion is an important component of glaucomatous optic nerve excavation. PMID:25531761

  9. Ethnic specific association of the CAV1/CAV2 locus with primary open-angle glaucoma

    PubMed Central

    Rong, Shi Song; Chen, Li Jia; Leung, Christopher K. S.; Matsushita, Kenji; Jia, Liyun; Miki, Atsuya; Chiang, Sylvia W. Y.; Tam, Pancy O. S.; Hashida, Noriyasu; Young, Alvin L.; Tsujikawa, Motokazu; Zhang, Mingzhi; Wang, Ningli; Nishida, Kohji; Pang, Chi Pui

    2016-01-01

    A single-nucleotide polymorphism (SNP) rs4236601 at the CAV1/CAV2 locus is associated with primary open-angle glaucoma (POAG). Rs4236601 is common in Caucasians but rare in East Asians. Here we conducted a haplotype-tagging SNP analysis followed by replication in a total of 848 POAG cases and 1574 controls drawn from 3 cities in China and 1 city in Japan. Two SNPs, rs4236601 (odds ratio [OR] = 6.25; P = 0.0086) and a tagging-SNP rs3801994 (OR = 1.32; P = 0.042), were associated with POAG in the Hong Kong Chinese cohort after age and gender adjustments. Rs4236601 was associated with POAG also in Shantou (OR = 6.09; P = 0.0037) and Beijing (OR = 3.92; P = 0.030) cohorts after age and gender adjustment, with a pooled-OR of 5.26 (P = 9.0 × 10−6) in Chinese; but it is non-polymorphic in the Osaka cohort. SNP rs3801994 showed a similar trend of effect in the Shantou and Beijing cohorts, with a pooled-OR of 1.23 (P = 0.022) and 1.20 (P = 0.063) in Chinese, prior to and after age and gender adjustment, respectively; but it showed a reverse effect in the Osaka cohort (OR = 0.58; P = 0.033) after the adjustments. We have thus confirmed the association of rs4236601 with POAG in different Chinese cohorts. Also, we found a common SNP rs3801994 of diverse associations with POAG between Chinese and Japanese. PMID:27297022

  10. DNA Copy Number Variants of Known Glaucoma Genes in Relation to Primary Open-Angle Glaucoma

    PubMed Central

    Liu, Yutao; Garrett, Melanie E.; Yaspan, Brian L.; Bailey, Jessica Cooke; Loomis, Stephanie J.; Brilliant, Murray; Budenz, Donald L.; Christen, William G.; Fingert, John H.; Gaasterland, Douglas; Gaasterland, Terry; Kang, Jae H.; Lee, Richard K.; Lichter, Paul; Moroi, Sayoko E.; Realini, Anthony; Richards, Julia E.; Schuman, Joel S.; Scott, William K.; Singh, Kuldev; Sit, Arthur J.; Vollrath, Douglas; Weinreb, Robert; Wollstein, Gadi; Zack, Donald J.; Zhang, Kang; Pericak-Vance, Margaret A.; Haines, Jonathan L.; Pasquale, Louis R.; Wiggs, Janey L.; Allingham, R. Rand; Ashley-Koch, Allison E.; Hauser, Michael A.

    2014-01-01

    Purpose. We examined the role of DNA copy number variants (CNVs) of known glaucoma genes in relation to primary open angle glaucoma (POAG). Methods. Our study included DNA samples from two studies (NEIGHBOR and GLAUGEN). All the samples were genotyped with the Illumina Human660W_Quad_v1 BeadChip. After removing non–blood-derived and amplified DNA samples, we applied quality control steps based on the mean Log R Ratio and the mean B allele frequency. Subsequently, data from 3057 DNA samples (1599 cases and 1458 controls) were analyzed with PennCNV software. We defined CNVs as those ≥5 kilobases (kb) in size and interrogated by ≥5 consecutive probes. We further limited our investigation to CNVs in known POAG-related genes, including CDKN2B-AS1, TMCO1, SIX1/SIX6, CAV1/CAV2, the LRP12-ZFPM2 region, GAS7, ATOH7, FNDC3B, CYP1B1, MYOC, OPTN, WDR36, SRBD1, TBK1, and GALC. Results. Genomic duplications of CDKN2B-AS1 and TMCO1 were each found in a single case. Two cases carried duplications in the GAS7 region. Genomic deletions of SIX6 and ATOH7 were each identified in one case. One case carried a TBK1 deletion and another case carried a TBK1 duplication. No controls had duplications or deletions in these six genes. A single control had a duplication in the MYOC region. Deletions of GALC were observed in five cases and two controls. Conclusions. The CNV analysis of a large set of cases and controls revealed the presence of rare CNVs in known POAG susceptibility genes. Our data suggest that these rare CNVs may contribute to POAG pathogenesis and merit functional evaluation. PMID:25414181

  11. An updated meta-analysis: Apolipoprotein E genotypes and risk of primary open-angle glaucoma

    PubMed Central

    Liao, Rongfeng; Ye, Minjie

    2014-01-01

    Purpose To study the association of apolipoprotein E (APOE) polymorphisms and primary open-angle glaucoma (POAG). Methods After a systematic literature search, all relevant studies evaluating the association between APOE polymorphisms and POAG were included. All statistical tests were calculated with Stata 11.0. Results Twelve independent studies on the APOE gene (1,971 cases, 1,756 controls) and POAG were included. A significant association between the APOE gene and POAG was found in the genetic model of ε4/ε4 versus ε3/ε3 (odds ratio [OR] = 2.09, 95% confidence interval [CI] = 1.12–3.88, p = 0.02). However, no association was detected in the models of ε2/ε2 versus ε3/ε3, ε2/ε3 versus ε3/ε3, ε2/ε4 versus ε3/ε3, ε3/ε4 versus ε3/ε3, allele ε2 versus allele ε3, and allele ε4 versus allele ε3. Subgroup analyses showed that a statistically significant association between the APOE gene and the risk of POAG existed in the genetic model of ε4/ε4 versus ε3/ε3 in Asians (OR = 3.55, 95% CI = 1.06–11.87, p = 0.04). No association was identified between the APOE gene and the risk of POAG in Caucasians. Conclusions The present meta-analysis indicated that the ε4/ε4 genotype is associated with increased risk of POAG in Asians. PMID:25053873

  12. Mitochondrial Sequence Variation in African-American Primary Open-Angle Glaucoma Patients

    PubMed Central

    Collins, David W.; Gudiseva, Harini V.; Trachtman, Benjamin T.; Jerrehian, Matthew; Gorry, Thomasine; Merritt III, William T.; Rhodes, Allison L.; Sankar, Prithvi S.; Regina, Meredith; Miller-Ellis, Eydie; O’Brien, Joan M.

    2013-01-01

    Primary open-angle glaucoma (POAG) is a major cause of blindness and results from irreversible retinal ganglion cell damage and optic nerve degeneration. In the United States, POAG is most prevalent in African-Americans. Mitochondrial genetics and dysfunction have been implicated in POAG, and potentially pathogenic sequence variations, in particular novel transversional base substitutions, are reportedly common in mitochondrial genomes (mtDNA) from POAG patient blood. The purpose of this study was to ascertain the spectrum of sequence variation in mtDNA from African-American POAG patients and determine whether novel nonsynonymous, transversional or other potentially pathogenic sequence variations are observed more commonly in POAG cases than controls. mtDNA from African-American POAG cases (n = 22) and age-matched controls (n = 22) was analyzed by deep sequencing of a single 16,487 base pair PCR amplicon by Ion Torrent, and candidate novel variants were validated by Sanger sequencing. Sequence variants were classified and interpreted using the MITOMAP compendium of polymorphisms. 99.8% of the observed variations had been previously reported. The ratio of novel variants to POAG cases was 7-fold lower than a prior estimate. Novel mtDNA variants were present in 3 of 22 cases, novel nonsynonymous changes in 1 of 22 cases and novel transversions in 0 of 22 cases; these proportions are significantly lower (p<.0005, p<.0004, p<.0001) than estimated previously for POAG, and did not differ significantly from controls. Although it is possible that mitochondrial genetics play a role in African-Americans’ high susceptibility to POAG, it is unlikely that any mitochondrial respiratory dysfunction is due to an abnormally high incidence of novel mutations that can be detected in mtDNA from peripheral blood. PMID:24146900

  13. Mitochondrial sequence variation in African-American primary open-angle glaucoma patients.

    PubMed

    Collins, David W; Gudiseva, Harini V; Trachtman, Benjamin T; Jerrehian, Matthew; Gorry, Thomasine; Merritt, William T; Rhodes, Allison L; Sankar, Prithvi S; Regina, Meredith; Miller-Ellis, Eydie; O'Brien, Joan M

    2013-01-01

    Primary open-angle glaucoma (POAG) is a major cause of blindness and results from irreversible retinal ganglion cell damage and optic nerve degeneration. In the United States, POAG is most prevalent in African-Americans. Mitochondrial genetics and dysfunction have been implicated in POAG, and potentially pathogenic sequence variations, in particular novel transversional base substitutions, are reportedly common in mitochondrial genomes (mtDNA) from POAG patient blood. The purpose of this study was to ascertain the spectrum of sequence variation in mtDNA from African-American POAG patients and determine whether novel nonsynonymous, transversional or other potentially pathogenic sequence variations are observed more commonly in POAG cases than controls. mtDNA from African-American POAG cases (n = 22) and age-matched controls (n = 22) was analyzed by deep sequencing of a single 16,487 base pair PCR amplicon by Ion Torrent, and candidate novel variants were validated by Sanger sequencing. Sequence variants were classified and interpreted using the MITOMAP compendium of polymorphisms. 99.8% of the observed variations had been previously reported. The ratio of novel variants to POAG cases was 7-fold lower than a prior estimate. Novel mtDNA variants were present in 3 of 22 cases, novel nonsynonymous changes in 1 of 22 cases and novel transversions in 0 of 22 cases; these proportions are significantly lower (p<.0005, p<.0004, p<.0001) than estimated previously for POAG, and did not differ significantly from controls. Although it is possible that mitochondrial genetics play a role in African-Americans' high susceptibility to POAG, it is unlikely that any mitochondrial respiratory dysfunction is due to an abnormally high incidence of novel mutations that can be detected in mtDNA from peripheral blood. PMID:24146900

  14. Ethnic specific association of the CAV1/CAV2 locus with primary open-angle glaucoma.

    PubMed

    Rong, Shi Song; Chen, Li Jia; Leung, Christopher K S; Matsushita, Kenji; Jia, Liyun; Miki, Atsuya; Chiang, Sylvia W Y; Tam, Pancy O S; Hashida, Noriyasu; Young, Alvin L; Tsujikawa, Motokazu; Zhang, Mingzhi; Wang, Ningli; Nishida, Kohji; Pang, Chi Pui

    2016-01-01

    A single-nucleotide polymorphism (SNP) rs4236601 at the CAV1/CAV2 locus is associated with primary open-angle glaucoma (POAG). Rs4236601 is common in Caucasians but rare in East Asians. Here we conducted a haplotype-tagging SNP analysis followed by replication in a total of 848 POAG cases and 1574 controls drawn from 3 cities in China and 1 city in Japan. Two SNPs, rs4236601 (odds ratio [OR] = 6.25; P = 0.0086) and a tagging-SNP rs3801994 (OR = 1.32; P = 0.042), were associated with POAG in the Hong Kong Chinese cohort after age and gender adjustments. Rs4236601 was associated with POAG also in Shantou (OR = 6.09; P = 0.0037) and Beijing (OR = 3.92; P = 0.030) cohorts after age and gender adjustment, with a pooled-OR of 5.26 (P = 9.0 × 10(-6)) in Chinese; but it is non-polymorphic in the Osaka cohort. SNP rs3801994 showed a similar trend of effect in the Shantou and Beijing cohorts, with a pooled-OR of 1.23 (P = 0.022) and 1.20 (P = 0.063) in Chinese, prior to and after age and gender adjustment, respectively; but it showed a reverse effect in the Osaka cohort (OR = 0.58; P = 0.033) after the adjustments. We have thus confirmed the association of rs4236601 with POAG in different Chinese cohorts. Also, we found a common SNP rs3801994 of diverse associations with POAG between Chinese and Japanese. PMID:27297022

  15. 193 nm excimer laser sclerostomy in pseudophakic patients with advanced open angle glaucoma.

    PubMed Central

    Allan, B D; van Saarloos, P P; Cooper, R L; Constable, I J

    1994-01-01

    A modified open mask system incorporating an en face air jet to dry the target area during ablation and a conjunctival plication mechanism, which allows ab externo delivery of the 193 nm excimer laser without prior conjunctival dissection, has been developed to form small bore sclerostomies accurately and atraumatically. Full thickness sclerostomies, and sclerostomies guarded by a smaller internal ostium can be created. A pilot therapeutic trial was conducted in pseudophakic patients with advanced open angle glaucoma. Six full thickness sclerostomies (200 microns and 400 microns diameter) and three guarded sclerostomies were created in nine patients by 193 nm excimer laser ablation (fluence per pulse 400 mJ/cm2, pulse rate 16 Hz, air jet pressure intraocular pressure +25 mm Hg). After 6 months' follow up, intraocular pressure was controlled (< or = 16 mm Hg) in eight of the nine patients (6/9 without medication). Early postoperative complications included hyphaema (trace--2.5 mm) (6/9), temporary fibrinous sclerostomy occlusion (4/9), profound early hypotony (all patients without fibrinous occlusion), and suprachoroidal haemorrhage in one case. Conjunctival laser wounds were self sealing. Small bore laser sclerostomy procedures are functionally equivalent to conventional full thickness procedures, producing early postoperative hypotony, with an increased risk of suprachoroidal haemorrhage in association with this. Further research is required to improve control over internal guarding in excimer laser sclerostomy before clinical trials of this technique can safely proceed. Images PMID:8148335

  16. 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

  17. 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

  18. 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

  19. Relationship between visual field progression and baseline refraction in primary open-angle glaucoma

    PubMed Central

    Naito, Tomoko; Yoshikawa, Keiji; Mizoue, Shiro; Nanno, Mami; Kimura, Tairo; Suzumura, Hirotaka; Umeda, Yuzo; Shiraga, Fumio

    2016-01-01

    Purpose To analyze the relationship between visual field (VF) progression and baseline refraction in Japanese patients with primary open-angle glaucoma (POAG) including normal-tension glaucoma. Patients and methods In this retrospective study, the subjects were patients with POAG who had undergone VF tests at least ten times with a Humphrey Field Analyzer (Swedish interactive thresholding algorithm standard, Central 30-2 program). VF progression was defined as a significantly negative value of mean deviation (MD) slope at the final VF test. Multivariate logistic regression models were applied to detect an association between MD slope deterioration and baseline refraction. Results A total of 156 eyes of 156 patients were included in this analysis. Significant deterioration of MD slope was observed in 70 eyes of 70 patients (44.9%), whereas no significant deterioration was evident in 86 eyes of 86 patients (55.1%). The eyes with VF progression had significantly higher baseline refraction compared to those without apparent VF progression (−1.9±3.8 diopter [D] vs −3.5±3.4 D, P=0.0048) (mean ± standard deviation). When subject eyes were classified into four groups by the level of baseline refraction applying spherical equivalent (SE): no myopia (SE > −1D), mild myopia (−1D ≥ SE > −3D), moderate myopia (−3D ≥ SE > −6D), and severe myopia (−6D ≥ SE), the Cochran–Armitage trend analysis showed a decreasing trend in the proportion of MD slope deterioration with increasing severity of myopia (P=0.0002). The multivariate analysis revealed that baseline refraction (P=0.0108, odds ratio [OR]: 1.13, 95% confidence interval [CI]: 1.03–1.25) and intraocular pressure reduction rate (P=0.0150, OR: 0.97, 95% CI: 0.94–0.99) had a significant association with MD slope deterioration. Conclusion In the current analysis of Japanese patients with POAG, baseline refraction was a factor significantly associated with MD slope deterioration as well as intraocular

  20. 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.

  1. Association of known common genetic variants with primary open angle, primary angle closure, and pseudoexfoliation glaucoma in Pakistani cohorts

    PubMed Central

    Micheal, Shazia; Ayub, Humaira; Khan, Muhammad Imran; Bakker, Bjorn; Schoenmaker-Koller, Frederieke E.; Ali, Mahmood; Akhtar, Farah; Khan, Wajid Ali; Qamar, Raheel

    2014-01-01

    Purpose Despite the different etiology of primary open angle glaucoma (POAG), primary angle closure glaucoma (PACG), and pseudoexfoliative glaucoma (PEXG), several studies have suggested that these forms of glaucoma have overlapping genetic risk factors. Therefore, the aim of this study was to evaluate the role of genetic variants recently associated with POAG in different types of glaucoma in Pakistani POAG, PACG, and PEXG patient cohorts. Methods Six variants in CDKN2B-AS1 (rs4977756), CDKN2B (rs1063192), ATOH7 (rs1900004), CAV1 (rs4236601), TMCO1 (rs4656461), and SIX1 (rs10483727) were genotyped using TaqMan assays. A total of 513 unrelated patients with glaucoma (268 with POAG, 125 with PACG, and 120 with PEXG) and 233 healthy controls were included in the study. Genotypic and allelic associations were analyzed with a chi-square test. Results The frequency of the G allele of TMCO1 rs4656461 was significantly lower in the patients with POAG (p=0.003; OR [odds ratio]=0.57), PACG (p=0.009; OR=0.52), and PEXG (p=0.01; OR=0.54) compared to the control individuals. The T allele of ATOH7 rs1900004 was observed less frequently in the patients with PACG (p=0.03; OR=0.69) compared to the control individuals. The A allele of CAV1 rs4236601 was found more frequently in the patients with POAG (p=0.008; OR=1.49) compared to the control individuals. This study demonstrates that the TMCO1 rs4656461 variant is associated with POAG, PACG and PEXG in the Pakistani population. Our study was unable to confirm previous associations reported for variants in CDKN2B-AS1, CDKN2B, and SIX1 with any type of glaucoma. Conclusions In conclusion, we found consistent evidence of the significant association of three common variants in TMCO1, ATOH7, and CAV1. PMID:25489222

  2. Primary open angle glaucoma due to T377M MYOC: Population mapping of a Greek founder mutation in Northwestern Greece

    PubMed Central

    Kitsos, George; Petrou, Zacharias; Grigoriadou, Maria; Samples, John R; Hewitt, Alex W; Kokotas, Haris; Giannoulia-Karantana, Aglaia; Mackey, David A; Wirtz, Mary K; Moschou, Marilita; Ioannidis, John PA; Petersen, Michael B

    2010-01-01

    Background: Mutations in the MYOC gene have been shown to explain 5% of unrelated primary open angle glaucoma (POAG) in different populations. In particular, the T377M MYOC mutation has arisen at least three separate times in history, in Great Britain, India, and Greece. The purpose of this study is to investigate the distribution of the mutation among different population groups in the northwestern region of Greece. Materials and methods: We explored the distribution of the “Greek” T377M founder mutation in the Epirus region in Northwestern Greece, which could be its origin. Genotyping was performed in POAG cases and controls by PCR amplification of the MYOC gene, followed by digestion with restriction enzyme. Statistical analyses were performed by an exact test, the Kaplan–Meier method and the t-test. Results: In the isolated Chrysovitsa village in the Pindus Mountains, a large POAG family demonstrated the T377M mutation in 20 of 66 family members while no controls from the Epirus region (n = 124) carried this mutation (P < 0.001). Among other POAG cases from Epirus, 2 out of 14 familial cases and 1 out of 80 sporadic cases showed the mutation (P = 0.057). The probability of POAG diagnosis with advancing age among mutation carriers was 23% at age 40, and reached 100% at age 75. POAG patients with the T377M mutation were diagnosed at a mean age of 51 years (SD ± 13.9), which is younger than the sporadic or familial POAG cases: 63.1 (SD ± 11) and 66.8 (SD ± 9.8) years, respectively. Conclusions: The T377M mutation was found in high proportion in members of the Chrysovitsa family (30.3%), in lower proportion in familial POAG cases (14.2%) and seems rare in sporadic POAG cases (1.2%), while no controls (0%) from the Epirus region carried the mutation. Historical and geographical data may explain the distribution of this mutation within Greece and worldwide. PMID:20390039

  3. 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

  4. 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.

  5. Biodegradable 3D-Porous Collagen Matrix (Ologen) Compared with Mitomycin C for Treatment of Primary Open-Angle Glaucoma: Results at 5 Years

    PubMed Central

    Yuan, Fei; Li, Lei; Chen, Xiuping; Yan, Xiang; Wang, Liyang

    2015-01-01

    Purpose. To evaluate the effectiveness and safety of the Ologen as an aid for trabeculectomy performed for primary open-angle glaucoma compared with mitomycin C. Methods. In this prospective, randomized, parallel assignment, comparative study, 31 eyes of 21 primary open-angle glaucoma patients were allocated for trabeculectomy with the Ologen implant; another 32 eyes of 23 patients were treated with trabeculectomy augmented with mitomycin C. The patients were followed up for 5 years and evaluated for intraocular pressure, rate of success, status of the bleb, and adverse events. Result. The mean postoperative intraocular pressure was statistically different at 3 m, 6 m, 1 y, 3 y, and 5 y follow-up. The rates of both complete success (P = 0.017) and overall success (P = 0.031) in the Ologen group were significantly higher than those in the mitomycin C group. The difference of the bleb extent and vascularity was statistically significant in both groups. There was no significant difference in postoperative complication. Conclusions. Ologen provides higher rates of surgical success compared with mitomycin C for patients with primary open-angle glaucoma undergoing trabeculectomy. It may be a new, safe, simple, and effective therapeutic approach for treating primary open-angle glaucoma. PMID:26078875

  6. 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

  7. Comparison of Schlemm's canal's biological parameters in primary open-angle glaucoma and normal human eyes with swept source optical

    NASA Astrophysics Data System (ADS)

    Wang, Fei; Shi, Guohua; Li, Xiqi; Lu, Jing; Ding, Zhihua; Sun, Xinghuai; Jiang, Chunhui; Zhang, Yudong

    2012-11-01

    Thirty-seven normal and primary open angle glaucoma (POAG) subjects were noninvasively imaged by a tailor-made real-time anterior segment swept source optical coherence tomography (SS-OCT) to demonstrate the differences of the Schlemm's canal (SC) between POAG and normal eyes. After the cross-section images of the anterior chamber angle were acquired by SS-OCT, SC was confirmed by two independent masked observers and the average area, long diameter, and perimeter of the SC were measured. In normal subjects the circumference, area, and long diameter is 580.34±87.81 μm, 8023.89±1486.10 μ, and 272.83±49.39 μm, respectively, and these parameters were 393.25±98.04 μm, 3941.50±1210.69 μ, and 190.91±46.47 μm in the POAG subjects. The area of SC in the normal ones was significantly larger than that in POAG eyes (p<0.001), so as the long diameter and the perimeter (p<0.001 p<0.001).

  8. Macular Pigment Optical Density in Chinese Primary Open Angle Glaucoma Using the One-Wavelength Reflectometry Method

    PubMed Central

    Ji, Yuying; Zuo, Chengguo; Lin, Mingkai; Zhang, Xiongze; Li, Miaoling; Mi, Lan; Liu, Bing; Wen, Feng

    2016-01-01

    Purpose. To investigate macular pigment optical density (MPOD) and its relationship with retinal thickness in primary open angle glaucoma (POAG) patients using the one-wavelength reflectometry method. Methods. A total of 30 eyes from 30 POAG patients (18 males and 12 females, mean age 47.27 ± 16.93) and 52 eyes from 52 controls (27 males and 25 females, mean age 49.54 ± 19.15) were included in this prospective, observational, case-control study. MPOD was measured in a 7-degree area using one-wavelength reflectometry method. Two parameters, max and mean optical density (OD), were used for analyses. Spectral-domain-optical coherence tomography was used to measure retinal thickness, including central retinal thickness (CRT), the macular ganglion cell complex (GCC), and the circumpapillary retinal nerve fiber layer (RNFL). Results. Both maxOD and meanOD were significantly reduced in POAG patients compared with normal subjects (P < 0.001). GCC, CRT, and RNFL thicknesses were also significantly reduced in POAG patients (P < 0.001). GCC thickness had a positive relationship with MPOD. Conclusions. MPOD within the 7-degree area was significantly lower in Chinese POAG patients than in control subjects, and GCC thickness was significantly and positively associated with MPOD. Whether the observed lower MPOD in POAG contributes to the disease process or is secondary to pathological changes caused by the disease (such as loss of ganglion cells) warrants further and longitudinal study. PMID:27144013

  9. Family-based analysis identified CD2 as a susceptibility gene for primary open angle glaucoma in Chinese Han population

    PubMed Central

    Liu, Ting; Xie, Lin; Ye, Jian; He, Xiangge

    2014-01-01

    Primary open angle glaucoma (POAG) is characterized by optic disc cupping and irreversible loss of retinal ganglion cells. Few genes have been detected that influence POAG susceptibility and little is known about its genetic architecture. In this study, we employed exome sequencing on three members from a high frequency POAG family to identify the risk factors of POAG in Chinese population. Text-mining method was applied to identify genes associated with glaucoma in literature, and protein–protein interaction networks were constructed. Furthermore, reverse transcription PCR and Western blot were performed to confirm the differential gene expression. Six genes, baculoviral inhibitors of apoptosis protein repeat containing 6 (BIRC6), CD2, luteinizing hormone/choriogonadotropin receptor (LHCGR), polycystic kidney and hepatic disease gene 1 (PKHD1), phenylalanine hydroxylase (PAH) and fucosyltransferase 7 (FUT7), which might be associated with POAG, were identified. Both the mRNA expression levels and protein expression levels of HSP27 were increased in astrocytes from POAG patients compared with those from normal control, suggesting that mutation in CD2 might pose a risk for POAG in Chinese population. In conclusion, novel rare variants detected by exome sequencing may hold the key to unravelling the remaining contribution of genetics to complex diseases such as POAG. PMID:24597656

  10. 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

  11. Genome-Wide Linkage Scan for Primary Open Angle Glaucoma: Influences of Ancestry and Age at Diagnosis

    PubMed Central

    Qin, Xuejun; Liu, Yutao; Gibson, Jason R.; Santiago-Turla, Cecilia; Larocque-Abramson, Karen R.; Del Bono, Elizabeth; Challa, Pratap; Herndon, Leon W.; Akafo, Stephen; Wiggs, Janey L.; Schmidt, Silke; Hauser, Michael A.

    2011-01-01

    Primary open-angle glaucoma (POAG) is the most common form of glaucoma and one of the leading causes of vision loss worldwide. The genetic etiology of POAG is complex and poorly understood. The purpose of this work is to identify genomic regions of interest linked to POAG. This study is the largest genetic linkage study of POAG performed to date: genomic DNA samples from 786 subjects (538 Caucasian ancestry, 248 African ancestry) were genotyped using either the Illumina GoldenGate Linkage 4 Panel or the Illumina Infinium Human Linkage-12 Panel. A total of 5233 SNPs was analyzed in 134 multiplex POAG families (89 Caucasian ancestry, 45 African ancestry). Parametric and non-parametric linkage analyses were performed on the overall dataset and within race-specific datasets (Caucasian ancestry and African ancestry). Ordered subset analysis was used to stratify the data on the basis of age of glaucoma diagnosis. Novel linkage regions were identified on chromosomes 1 and 20, and two previously described loci—GLC1D on chromosome 8 and GLC1I on chromosome 15—were replicated. These data will prove valuable in the context of interpreting results from genome-wide association studies for POAG. PMID:21765929

  12. Evaluation of genetic association of the INK4 locus with primary open angle glaucoma in East Indian population.

    PubMed

    Vishal, Mansi; Sharma, Anchal; Kaurani, Lalit; Chakraborty, Subhadip; Ray, Jharna; Sen, Abhijit; Mukhopadhyay, Arijit; Ray, Kunal

    2014-01-01

    INK4 locus at chromosome 9p21 has been reported to be associated with primary open angle glaucoma (POAG) and its subtypes along with the associated optic disc parameters across the populations of European, Japanese and African ancestries. The locus encodes three tumor suppressor genes namely CDKN2A, ARF, CDKN2B and a long non-coding RNA CDKN2B-AS1 (also known as ANRIL). Here, we report association study of 34 SNPs from INK4 locus with POAG in a population of Indo-European ancestry from the eastern part of India (350 patients and 354 controls). With 81% power to detect genetic association we observed only nominal association of rs1011970 (uncorrected p = 0.048) with POAG and rs10120688 (uncorrected p = 0.048) in patients without a high intra-ocular pressure (IOP<21 mm of Hg) compared to controls. This study, in contrast to the previous reports, suggests lack of significant genetic association of INK4 locus with POAG in East Indian population which needs to be replicated in larger studies in diverse world populations. PMID:24875940

  13. Intraocular Pressure-Lowering Potential of Subthreshold Selective Laser Trabeculoplasty in Patients with Primary Open-Angle Glaucoma

    PubMed Central

    Yang, Yang Fan; Xu, Jian Gang

    2016-01-01

    Purpose. To compare the efficacy of subthreshold and conventional selective laser trabeculoplasty (SLT) in lowering intraocular pressure (IOP) in the patients with primary open-angle glaucoma (POAG). Methods. Fifty-two eyes from fifty-two POAG patients were randomized into two groups, one group treated with subthreshold SLT using two-thirds of the conventional energy and the other one treated with the conventional energy. IOP was measured with the Goldmann tonometer and the anterior chamber inflammation was determined using laser flare meter. Results. The initial energy dosage used in subthreshold SLT group was significantly lower than the amount of the energy used in conventional SLT group (0.4 ± 0.1 mJ versus 0.6 ± 0.1 mJ, P = 0.030). The total energy dosage was also significantly lower in subthreshold SLT group compared to the other group (37.6 ± 3.3 mJ versus 51.8 ± 5.7 mJ, P = 0.036). However, the level of inflammation in aqueous humor, amount of reduction in IOP, and the success rate in controlling IOP was the same in both groups. Conclusion. The efficacy of subthreshold SLT group in reducing IOP in POAG patients is comparable to the efficacy of conventional SLT group. PMID:27529032

  14. Bimatoprost/timolol fixed combination (BTFC) in patients with primary open angle glaucoma or ocular hypertension in Greece

    PubMed Central

    Rotsos, Tryfon G.; Kliafa, Vasso G.; Asher, Kevin J.; Papaconstantinou, Dimitrios

    2016-01-01

    AIM To evaluate the efficacy and tolerability of the fixed combination of bimatoprost 0.03% and timolol 0.5% (BTFC) in patients in Greece with primary open angle glaucoma (POAG) or ocular hypertension (OHT) whose previous therapy provided insufficient lowering of intraocular pressure (IOP). METHODS A multicenter, prospective, open-label, non-interventional, observational study of the use of BTFC in clinical practice was conducted at 41 sites in Greece. The primary endpoint was the reduction in IOP from baseline at study end, approximately 12wk after initiation of BTFC therapy. RESULTS A total of 785 eligible patients were enrolled in the study and 97.6% completed the study. The mean±SD IOP reduction from baseline at 12wk after initiation of BTFC was 6.3±2.8 mm Hg (n=764; P<0.001). In patients (n=680) who replaced their previous IOP-lowering monotherapy (a single drug, or a fixed combination of 2 drugs in a single ophthalmic drop) with once-daily BTFC, the mean±SD IOP reduction from baseline at 12wk was 6.2±2.8 mm Hg (P<0.001). IOP was reduced from baseline in 99.2% of patients, and 58.0% of patients reached or exceeded their target IOP. Substantial mean IOP reductions were observed regardless of the previous therapy. BTFC was well tolerated, with 96.0% of patients who completed the study rating the tolerability of BTFC as “good” or “very good.” Adverse events were reported in 8.3% of patients; only 0.6% of patients discontinued the study due to adverse events. CONCLUSION In clinical practice in Greece, BTFC is well tolerated and effectively lower the IOP in patients with POAG or OHT who requires additional IOP lowering on their previous therapy. PMID:26949613

  15. 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.

  16. 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

  17. Comparison of ab externo trabeculotomy in primary open-angle glaucoma and uveitic glaucoma: long-term outcomes

    PubMed Central

    William, Antony; Spitzer, Martin S; Doycheva, Deshka; Dimopoulos, Spyridon; Leitritz, Martin Alexander; Voykov, Bogomil

    2016-01-01

    Background The aim of this study was to compare the long-term outcomes of ab externo trabeculotomy in primary open-angle glaucoma (POAG) and uveitic glaucoma (UG). Design This was a retrospective single-center case series study. Participants Twenty eyes of 17 patients with POAG and 22 eyes of 18 patients with UG were included in this study. Patients and methods The medical records of all consecutive patients with POAG and UG who underwent ab externo trabeculotomy since 2004 were reviewed. Main outcome measure The main outcome measure was change in median intraocular pressure (IOP). Success was defined as IOP ≤21 mmHg (success 1) and IOP ≤21 mmHg and at least 25% reduction from baseline (success 2). Results In the POAG group, the median IOP decreased significantly from 22 mmHg (95% CI 21–25 mmHg; n=20) at baseline to 14 mmHg (95% CI 12–16; n=13) after 4 years, P<0.001. In the UG group, the median IOP decreased significantly from 27 mmHg (95% CI 24.5–30.5 mmHg; n=22) at baseline to 12 mmHg (95% CI 9–15 mmHg; n=15) after 4 years, P<0.001. Seven eyes in the UG group failed within the first year after surgery compared to none in the POAG group. Of these, four eyes had Fuchs’ uveitis syndrome and two had granulomatous uveitis. No sight-threatening complications occurred in both POAG and UG groups. Conclusion Ab externo trabeculotomy effectively reduced IOP in both UG and POAG groups. However, the success rates in the UG group were significantly lower due to the high failure rate in patients with Fuchs’ uveitis syndrome and granulomatous uveitis. The procedure demonstrated a high safety profile in both UG and POAG patients. PMID:27284237

  18. Age-based analysis of choroidal thickness and choroidal vessel diameter in primary open-angle glaucoma.

    PubMed

    Toprak, Ibrahim; Yaylalı, Volkan; Yildirim, Cem

    2016-04-01

    We aimed to assess choroidal thickness and vessel diameter in patients with primary open-angle glaucoma (POAG) using enhanced depth imaging (EDI) optical coherence tomography (OCT) with age-based analysis. Fifty-four patients with a confirmed diagnosis of POAG and 44 age-sex matched healthy subjects were included into the study. A masked physician performed measurements of largest choroidal vessel diameter and choroidal thicknesses (subfoveal, nasal, and temporal) using EDI OCT. Subgroup analyses were performed to compare choroidal measurements based on age (with a cut point of 70 years). The study cohort comprised 54 patients with POAG (mean age of 63.2 ± 8.8 years) and 44 healthy control subjects (mean age of 62.9 ± 8.5 years) (P = 0.870). We found no significant differences in terms of choroidal measurements (P > 0.05) between the glaucoma and control groups. However, in the glaucoma group, patients with an age ≥70 years had significantly thinner subfoveal and nasal choroid compared to those of the patients with <70 years of age (P = 0.017, 0.002 respectively). In the control group, choroidal thickness and vessel measurements showed no significant difference when the subjects were subgrouped according to the age cut point (P > 0.05). Choroidal thickness and vessel caliber seem not to differ between patients with POAG and healthy controls. However, an age ≥70 years might be associated with thinning in subfoveal and nasal choroid in patients with POAG. Further studies are needed to elucidate whether choroidal thinning is a cause or result in POAG. PMID:26077882

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

    PubMed

    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

  20. 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

  1. Estrogen pathway polymorphisms in relation to primary open angle glaucoma: An analysis accounting for gender from the United States

    PubMed Central

    Loomis, Stephanie J.; Weinreb, Robert N.; Kang, Jae H.; Yaspan, Brian L.; Bailey, Jessica Cooke; Gaasterland, Douglas; Gaasterland, Terry; Lee, Richard K.; Scott, William K.; Lichter, Paul R.; Budenz, Donald L.; Liu, Yutao; Realini, Tony; Friedman, David S.; McCarty, Catherine A.; Moroi, Sayoko E.; Olson, Lana; Schuman, Joel S.; Singh, Kuldev; Vollrath, Douglas; Wollstein, Gadi; Zack, Donald J.; Brilliant, Murray; Sit, Arthur J.; Christen, William G.; Fingert, John; Kraft, Peter; Zhang, Kang; Allingham, R. Rand; Pericak-Vance, Margaret A.; Richards, Julia E.; Hauser, Michael A.; Haines, Jonathan L.; Wiggs, Janey L.

    2013-01-01

    Purpose Circulating estrogen levels are relevant in glaucoma phenotypic traits. We assessed the association between an estrogen metabolism single nucleotide polymorphism (SNP) panel in relation to primary open angle glaucoma (POAG), accounting for gender. Methods We included 3,108 POAG cases and 3,430 controls of both genders from the Glaucoma Genes and Environment (GLAUGEN) study and the National Eye Institute Glaucoma Human Genetics Collaboration (NEIGHBOR) consortium genotyped on the Illumina 660W-Quad platform. We assessed the relation between the SNP panels representative of estrogen metabolism and POAG using pathway- and gene-based approaches with the Pathway Analysis by Randomization Incorporating Structure (PARIS) software. PARIS executes a permutation algorithm to assess statistical significance relative to the pathways and genes of comparable genetic architecture. These analyses were performed using the meta-analyzed results from the GLAUGEN and NEIGHBOR data sets. We evaluated POAG overall as well as two subtypes of POAG defined as intraocular pressure (IOP) ≥22 mmHg (high-pressure glaucoma [HPG]) or IOP <22 mmHg (normal pressure glaucoma [NPG]) at diagnosis. We conducted these analyses for each gender separately and then jointly in men and women. Results Among women, the estrogen SNP pathway was associated with POAG overall (permuted p=0.006) and HPG (permuted p<0.001) but not NPG (permuted p=0.09). Interestingly, there was no relation between the estrogen SNP pathway and POAG when men were considered alone (permuted p>0.99). Among women, gene-based analyses revealed that the catechol-O-methyltransferase gene showed strong associations with HTG (permuted gene p≤0.001) and NPG (permuted gene p=0.01). Conclusions The estrogen SNP pathway was associated with POAG among women. PMID:23869166

  2. Effect of dorzolamide and timolol on ocular blood flow in patients with primary open angle glaucoma and ocular hypertension

    PubMed Central

    Fuchsjäger-Mayrl, G; Wally, B; Rainer, G; Buehl, W; Aggermann, T; Kolodjaschna, J; Weigert, G; Polska, E; Eichler, H-G; Vass, C; Schmetterer, L

    2005-01-01

    Background: There is evidence that perfusion abnormalities of the optic nerve head are involved in the pathogenesis of glaucoma. There is therefore considerable interest in the effects of topical antiglaucoma drugs on ocular blood flow. A study was undertaken to compare the ocular haemodynamic effects of dorzolamide and timolol in patients with primary open angle glaucoma (POAG) or ocular hypertension (OHT). Methods: One hundred and forty patients with POAG or OHT were included in a controlled, randomised, double blind study in two parallel groups; 70 were randomised to receive timolol and 70 to receive dorzolamide for a period of 6 months. Subjects whose intraocular pressure (IOP) did not respond to either of the two drugs were switched to the alternative treatment after 2 weeks. Scanning laser Doppler flowmetry was used to measure blood flow in the temporal neuroretinal rim and the cup of the optic nerve head. Pulsatile choroidal blood flow was assessed using laser interferometric measurement of fundus pulsation amplitude. Results: Five patients did not respond to timolol and were changed to the dorzolamide group, and 18 patients changed from dorzolamide treatment to timolol. The effects of both drugs on IOP and ocular perfusion pressure were comparable. Dorzolamide, but not timolol, increased blood flow in the temporal neuroretinal rim (8.5 (1.6)%, p<0.001 versus timolol) and the cup of the optic nerve head (13.5 (2.5)%, p<0.001 versus timolol), and fundus pulsation amplitude (8.9 (1.3)%, p<0.001 versus timolol). Conclusions: This study indicates augmented blood flow in the optic nerve head and choroid after 6 months of treatment with dorzolamide, but not with timolol. It remains to be established whether this effect can help to reduce visual field loss in patients with glaucoma. PMID:16170119

  3. Diabetes Pathology and Risk of Primary Open-Angle Glaucoma: Evaluating Causal Mechanisms by Using Genetic Information.

    PubMed

    Shen, Ling; Walter, Stefan; Melles, Ronald B; Glymour, M Maria; Jorgenson, Eric

    2016-01-15

    Although type 2 diabetes (T2D) predicts glaucoma, the potential for unmeasured confounding has hampered causal conclusions. We performed separate sample genetic instrumental variable analyses using the Genetic Epidemiology Research Study on Adult Health and Aging cohort (n = 69,685; 1995-2013) to estimate effects of T2D on primary open-angle glaucoma (POAG; 3,554 cases). Genetic instrumental variables for overall and mechanism-specific (i.e., linked to T2D via influences on adiposity, β-cell function, insulin regulation, or other metabolic processes) T2D risk were constructed by using 39 genetic polymorphisms established to predict T2D in other samples. Instrumental variable estimates indicated that T2D increased POAG risk (odds ratio = 2.53, 95% confidence interval: 1.04, 6.11). The instrumental variable for β-cell dysregulation also significantly predicted POAG (odds ratioβ-cell = 5.26, 95% confidence interval: 1.75, 15.85), even among individuals without diagnosed T2D, suggesting that metabolic dysregulation may increase POAG risk prior to T2D diagnosis. The T2D risk variant in the melatonin receptor 1B gene (MTNR1B) predicted risk of POAG independently of T2D status, indicating possible pleiotropic physiological functions of melatonin, but instrumental variable effect estimates were significant even excluding MTNR1B variants. To our knowledge, this is the first genetic instrumental variable study of T2D and glaucoma, providing a novel approach to evaluating this hypothesized relationship. Our findings substantially bolster observational evidence that T2D increases POAG risk. PMID:26608880

  4. Correlations between corneal and optic nerve head variables in healthy subjects and patients with primary open angle glaucoma

    PubMed Central

    Saenz-Frances, Federico; Jañez, Luis; Borrego-Sanz, Lara; Berrozpe-Villabona, Clara; Martinez-de-la-Casa, Jose Maria; Morales-Fernandez, Laura; Garcia-Sanchez, Julian; Santos-Bueso, Enrique; Garcia-Feijoo, Julian

    2015-01-01

    AIM To correlate corneal variables (determined using the Pentacam) with optic nerve head (ONH) variables determined using the Heidelberg retina tomograph (HRT) in healthy subjects and patients diagnosed with primary open angle glaucoma (POAG). METHODS Measurements were made in 75 healthy eyes and 73 eyes with POAG and correlations examined through Pearson correlation coefficients between the two sets of variables in the two subject groups. The corneal variables determined were corneal volume (CVol), central corneal thickness (CCT), overall corneal thickness (OvCT), the mean thickness of a circular zone centered at the corneal apex of 1 mm radius (zone I) and the mean thickness of several concentric rings, also centered at the apex until the limbus, each of 1 mm width (zones II to VI respectively). The ONH variables were determined using the HRT. RESULTS The following pairs of variables were correlated in the control group: CCT-disc area (DAr) (-0.48; P<0.0001), Zone I-DAr (-0.503; P<0.0001) and Zone II-DAr (-0.443; P<0.0001); and in the POAG group: CCT-cup-to-disc area ratio (CDRa) (-0.402; P<0.0001), Zone I-CDRa (-0.418; P<0.0001), Zone II-CDRa (-0.405; P=0.006), Zone I-cup shape measure (CSM) (-0.415; P=0.002), Zone II-CSM (-0.405; P=0.001), Zone IV-height variation contour (HVC) (0.378; P=0.002); Zone V-HVC (0.388, P<0.0001). CONCLUSIONS In the healthy subjects, significant negative correlation was detected between central and paracentral corneal thickness and optic disc area. In contrast, the POAG patients showed significant negative correlation between central and paracentral corneal thickness and the cup-disc ratio and CSM, and positive correlation between peripheral corneal thickness and HVC. PMID:26682165

  5. Selective laser trabeculoplasty in patients with pseudoexfoliative glaucoma vs primary open angle glaucoma: a one-year comparative study

    PubMed Central

    Miraftabi, Arezoo; Nilforushan, Naveed; Nassiri, Nariman; Nouri-Mahdavi, Kouros

    2016-01-01

    AIM To compare the efficacy of single-session 360-degree selective laser trabeculoplasty (SLT) for reduction of intraocular pressure (IOP) in patients with pseudoexfoliative glaucoma (PXFG) and primary open angle glaucoma (POAG). METHODS This is a single-center, prospective, nonrandomized comparative study. Patients older than 18 years of age with uncontrolled PXFG or POAG eyes requiring additional therapy while on maximally tolerated IOP-lowering medications were included. The primary outcome measure changed in IOP from baseline. Success was defined as IOP reduction ≥20% from baseline without any additional IOP-lowering medication. All patients were examined at 1d, 1wk, 1, 3, 6, 9, 12mo after SLT. RESULTS Nineteen patients (20 eyes) with PXFG and 27 patients (28 eyes) with POAG were included in the study. In the visual fields mean deviation was -2.88 (±1.67) in the POAG and -3.1 (±1.69) in the PXFG groups (P=0.3). The mean (±SD) IOP was 22.9 (±3.7) mm Hg in the POAG group and 25.7 (±4.4) mm Hg in the PXFG group at baseline and decreased to 18.4 (±3.2) and 18.0 (±3.9) mm Hg in the POAG group (P<0.001 and P=0.02), and to 17.9 (±4.0) and 21.0 (±6.6) mm Hg in the PXFG group (P<0.001 and P=0.47) at 6 and 12mo, respectively. The number of medications was 2.6 (±0.8) in the POAG group and 2.5 (±0.8) in the PXFG group at baseline, and did not change at all follow-up visits in both groups (P=0.16 in POAG and 0.57 in PXFG). Based on Kaplan-Meier survival analysis, the success rate was 75% in the POAG group compared to 94.1% in the PXFG group (P=0.08; log rank test) at 6mo, and 29.1% and 25.0% at 12mo, respectively (P=0.9; log rank). CONCLUSION The 360-degree SLT is an effective and well-tolerated therapeutic modality in patients with POAG and PXFG by reducing IOP without any change in number of medications. The response was more pronounced early in the postoperative period in patients with PXFG whereas there was no statistically significant difference at 12

  6. 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

  7. A Novel Genome-Wide Association Study Approach Using Genotyping by Exome Sequencing Leads to the Identification of a Primary Open Angle Glaucoma Associated Inversion Disrupting ADAMTS17

    PubMed Central

    Forman, Oliver P.; Pettitt, Louise; Komáromy, András M.; Bedford, Peter; Mellersh, Cathryn

    2015-01-01

    Closed breeding populations in the dog in conjunction with advances in gene mapping and sequencing techniques facilitate mapping of autosomal recessive diseases and identification of novel disease-causing variants, often using unorthodox experimental designs. In our investigation we demonstrate successful mapping of the locus for primary open angle glaucoma in the Petit Basset Griffon Vendéen dog breed with 12 cases and 12 controls, using a novel genotyping by exome sequencing approach. The resulting genome-wide association signal was followed up by genome sequencing of an individual case, leading to the identification of an inversion with a breakpoint disrupting the ADAMTS17 gene. Genotyping of additional controls and expression analysis provide strong evidence that the inversion is disease causing. Evidence of cryptic splicing resulting in novel exon transcription as a consequence of the inversion in ADAMTS17 is identified through RNAseq experiments. This investigation demonstrates how a novel genotyping by exome sequencing approach can be used to map an autosomal recessive disorder in the dog, with the use of genome sequencing to facilitate identification of a disease-associated variant. PMID:26683476

  8. A Novel Genome-Wide Association Study Approach Using Genotyping by Exome Sequencing Leads to the Identification of a Primary Open Angle Glaucoma Associated Inversion Disrupting ADAMTS17.

    PubMed

    Forman, Oliver P; Pettitt, Louise; Komáromy, András M; Bedford, Peter; Mellersh, Cathryn

    2015-01-01

    Closed breeding populations in the dog in conjunction with advances in gene mapping and sequencing techniques facilitate mapping of autosomal recessive diseases and identification of novel disease-causing variants, often using unorthodox experimental designs. In our investigation we demonstrate successful mapping of the locus for primary open angle glaucoma in the Petit Basset Griffon Vendéen dog breed with 12 cases and 12 controls, using a novel genotyping by exome sequencing approach. The resulting genome-wide association signal was followed up by genome sequencing of an individual case, leading to the identification of an inversion with a breakpoint disrupting the ADAMTS17 gene. Genotyping of additional controls and expression analysis provide strong evidence that the inversion is disease causing. Evidence of cryptic splicing resulting in novel exon transcription as a consequence of the inversion in ADAMTS17 is identified through RNAseq experiments. This investigation demonstrates how a novel genotyping by exome sequencing approach can be used to map an autosomal recessive disorder in the dog, with the use of genome sequencing to facilitate identification of a disease-associated variant. PMID:26683476

  9. TIMP1, TIMP2, and TIMP4 are increased in aqueous humor from primary open angle glaucoma patients

    PubMed Central

    Briggs, Esther L. Ashworth; Toh, Tze’Yo; Eri, Rajaraman; Hewitt, Alex W.

    2015-01-01

    Purpose Elevated intraocular pressure (IOP) is the only known modifiable risk factor for primary open angle glaucoma (POAG), and it can be caused by reduced aqueous humor outflow from the anterior chamber. Outflow is predominantly regulated by the trabecular meshwork, consisting of specialized cells within a complex extracellular matrix (ECM). An imbalance between ECM-degrading matrix metalloproteinases (MMPs) and the tissue inhibitors of MMPs (TIMPs) within the trabecular meshwork is thought to contribute to POAG. This study aimed to quantify levels of TIMPs and MMPs in aqueous humor samples from glaucomatous and non-glaucomatous eyes, analyze MMP/TIMP ratios, and correlate results with age, IOP, and Humphrey’s visual field pattern standard deviation (PSD). Methods Aqueous humor samples were collected from 26 non-glaucomatous control subjects before cataract surgery and 23 POAG patients undergoing trabeculectomy or cataract surgery. Analyte concentrations were measured using multiplexed immunoassays. Statistical significance was assessed with Mann–Whitney U tests, and Spearman’s method was used to assess correlations with age, IOP, and PSD. Results Concentrations of TIMP1 (p = 0.0008), TIMP2 (p = 0.002), TIMP4 (p = 0.002), and MMP2 (p = 0.020) were significantly increased in aqueous humor samples from POAG versus cataract samples. For the majority of MMP/TIMP molar ratios calculated for the cataract group, TIMPs outweighed MMPs. In POAG, molar ratios of MMP2/TIMP1 (p = 0.007) and MMP9/TIMP1 (p = 0.005) showed a significant decrease, corresponding to an elevated excess of TIMPs over MMPs in POAG compared to cataract samples. Conversely, MMP2/TIMP3 (p = 0.045) and MMP3/TIMP3 (p = 0.032) molar ratios increased. Several MMP/TIMP molar ratios correlated with IOP (r = 0.476–0.609, p = 0.007–0.034) and PSD (r = -0.482 to −0.655, p = 0.005–0.046) in POAG samples and with age in cataract control samples. Conclusions An imbalance among MMPs and TIMPs was found

  10. A survey of preoperative blood tests in primary open-angle glaucoma patients versus cataract surgery patients

    PubMed Central

    Cohen, Laura P.; Wong, Jessica; Jiwani, Aliya Z.; Greenstein, Scott H.; Brauner, Stacey C.; Chen, Sherleen C.; Turalba, Angela V.; Chen, Teresa C.; Shen, Lucy; Rhee, Douglas J.; Wiggs, Janey L.; Kang, Jae Hee; Loomis, Stephanie; Pasquale, Louis R.

    2014-01-01

    Purpose To investigate biomarker differences in routine preoperative blood tests performed on primary open-angle glaucoma (POAG) case and control patients presenting for anterior segment eye surgery. Methods POAG cases and age-related cataract surgery patients (controls) who underwent anterior segment surgery at Massachusetts Eye and Ear from January 2009 through March 2012 were identified by retrospective record review. Patients with diabetes mellitus, secondary glaucoma, and cataract due to trauma or steroid exposure were excluded. Data on demographic features, preoperative ophthalmological and medical diagnosis, blood pressure, anthropometric measures, basic metabolic panel, and complete blood count were extracted from the medical records. Univariate differences in lab values between POAG cases and controls were assessed using unpaired t tests. Multivariate logistic regression analysis was completed to determine the independent associations of biomarkers with POAG. Results A total of 150 cases and 150 age-related controls were included. In multivariate analysis, higher AG was inversely associated with POAG (odds ratio [OR] = 0.90; 95% confidence interval [CI], 0.80–1.00), and higher Cl− level was positively associated with POAG (OR = 1.15; 95% CI, 1.02–1.29). The lower AG in POAG patients could be explained by higher IgG levels as the available data in post hoc analysis showed a nonsignificant trend toward higher IgG in cases compared to controls (17 vs 23; 1142 ± 284 mg/dl vs 1028 ± 291 mg/dl; P = 0.22). Furthermore, in multivariable analysis, a higher red blood cell count was also associated with POAG (OR = 1.91; 95% CI, 1.11–3.28). Conclusions Patients with POAG presenting for anterior segment surgery had a lower AG compared to age-related cataract surgery patients. The etiology of this reduced gap is unclear but the possible contribution of IgG warrants further exploration. The etiology of higher red blood cell counts in POAG cases is unknown and

  11. Exclusion of one pedigree affected by adult onset primary open angle glaucoma from linkage to the juvenile glaucoma locus on chromosome 1q21-q31.

    PubMed Central

    Avramopoulos, D; Kitsos, G; Economou-Petersen, E; Grigoriadou, M; Vassilopoulos, D; Papageorgiou, C; Psilas, K; Petersen, M B

    1996-01-01

    A locus for autosomal dominant juvenile onset primary open angle glaucoma (POAG) was recently assigned to chromosome region 1q21-q31. In the present study, a large Greek family with autosomal dominant adult onset POAG was investigated using microsatellite markers. Exclusion of linkage of the adult onset POAG gene to the region D1S194-D1S191 was obtained in this pedigree. Therefore, the data provide evidence that juvenile and adult onset POAG are genetically distinct disease entities. PMID:9004141

  12. Polymorphisms in an intronic region of the myocilin gene associated with primary open-angle glaucoma—a possible role for alternate splicing

    PubMed Central

    Pandaranayaka, P.J. Eswari; Prasanthi, N.; Kannabiran, N.; Rangachari, K.; Dhivya, M.; Krishnadas, Subbiah R.; Sundaresan, P.

    2010-01-01

    Purpose To examine the possible role of alternate splicing leading to aggregation of myocilin in primary open-angle glaucoma. Methods Several single nucleotide variations found in the myocilin (MYOC) genomic region were collected and examined for their possible role in causing splice-site alterations. A model for myocilin built using a knowledge-based consensus method was used to map the altered protein products. A total of 150 open-angle glaucoma patients and 50 normal age-matched control subjects were screened for the predicted polymorphisms, and clustering was performed. Results A total of 124 genomic variations were screened, and six polymorphisms that lead to altered protein products were detected as possible candidates for the alternative splicing mechanism. Five of these lay in the intronic regions, and the one that lay in the exon region corresponded to the previously identified polymorphism (Tyr347Tyr) implicated in primary open-angle glaucoma. Experimentally screening the intronic region of the MYOC gene showed the presence of the predicted g.14072G>A polymorphism, g.1293C/T heterozygous polymorphism, instead of our predicted g.1293C/- polymorphism. Other than the prediction, two novel SNPs (g.1295G>T and g.1299T>G) and two reported SNPs (g.1284G>T and g.1286G>T) were also identified. Cluster analysis showed the g.14072G>A homozygous condition was more common in this cohort than the heterozygous condition. Conclusions We previously proposed that the disruption of dimer or oligomer formation by the C-term region allows greater chances of nucleation for aggregation. Here we suggest that polymorphisms in the myocilin genomic region that cause synonymous codon changes or those that occur in the intron regions can possibly lead to altered myocilin protein products through altered intron–exon splicing. PMID:21203411

  13. Impact of Socioeconomic Status on the Diagnosis of Primary Open-Angle Glaucoma and Primary Angle Closure Glaucoma: A Nationwide Population-Based Study in Taiwan

    PubMed Central

    Ko, Yu-Chieh; Hwang, De-Kuang; Chen, Wei-Ta

    2016-01-01

    Purpose To understand the impact of socioeconomic status (SES) on the diagnosis of primary open-angle glaucoma (POAG) and primary angle closure glaucoma (PACG) in Taiwan. Methods Subjects with glaucoma were identified from the National Health Insurance Research Database of year 2006, which included one million randomly selected insurants. Individuals who had ≥4 ambulatory visits within one year which had the diagnosis code of POAG (ICD-9-CM 365.11 or 365.12) or PACG (365.23) and concurrent prescription of anti-glaucoma medication or surgery were selected. Individual SES was represented by monthly income calculated from the insurance premium. Neighborhood SES was defined based on neighborhood household income averages. Urbanization level of habitation was categorized into 3 levels. The odds ratio of having POAG or PACG in subjects with different SES was evaluated by using multiple logistic regression analysis. Results In total, 752 and 561 subjects with POAG and PACG, respectively, who were treated on a regular basis, were identified. The diagnosis of glaucoma was affected by age, gender, frequency of healthcare utilization, individual SES, and urbanization level of habitation. With the adjustment of age, gender, healthcare utilization, neighborhood SES and level of urbanization, subjects with lower income were more likely to be diagnosed as PACG, but less likely as POAG. Conclusions Subjects with more frequent healthcare utilization were more likely to be diagnosed with glaucoma. Subjects with low SES were more susceptible to PACG, but subjects with high SES were more likely to be diagnosed as POAG. This information is useful for the design and target participant setting in glaucoma education and screening campaign to maximize the efficacy of limited resources in preventing glaucoma blindness. PMID:26905307

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. Efficacy and safety of prostaglandin analogues in patients with predominantly primary open-angle glaucoma or ocular hypertension: a meta-analysis

    PubMed Central

    Eyawo, Oghenowede; Nachega, Jean; Lefebvre, Pierre; Meyer, David; Rachlis, Beth; Lee, Chia-Wen; Kelly, Steven; Mills, Edward

    2009-01-01

    Background First-line therapy for primary open-angle glaucoma and ocular hypertension generally involves prostaglandin analogue therapy. The relative efficacy of differing prostaglandin therapy is disputed. Methods A meta-analysis was conducted of head-to-head randomized trials of prostaglandin therapies. We included randomized trials assessing head-to-head evaluations of prostaglandin analogues travoprost, latanoprost and bimatoprost in patients with predominantly primary open-angle glaucoma or ocular hypertension. Findings were interpreted in light of equivalence margins. Results Our search identified 16 eligible trials, of which 15 were included in the meta-analysis. Trials were, in general, poorly reported. We pooled 9 trials assessing IOP-lowering effects of travoprost vs latanoprost (total n = 1098, weighted mean difference [WMD], −0.24 mmHg, 95% CI, −0.87 to 0.38, P = 0.45, I2 = 56%, 95% CI, 0 to 0.77, heterogeneity P = 0.01). Eight trials assessed travoprost vs bimatoprost (total n = 714, WMD, 0.88 mmHg, 95% CI, 0.13 to 1.63, P = 0.02, I2 = 56%, 95% CI, 0% to 78%, heterogeneity P = 0.02). And 8 trials assessed latanoprost vs bimatoprost (total n = 943, WMD, 0.73 mmHg, 95% CI, 0.10 to 1.37, P = 0.02, I2 = 47%, 95% CI, 0% to 74%, heterogeneity P = 0.06). Travoprost was associated with greater incidence of conjunctival hyperemia than latanoprost (RR 5.71, 95% CI, 1.81 to 18.02, P ≤ 0.001, I2 = 97%, 95% CI, 95 to 98, P ≤ 0.001). Five trials assessing latanoprost and bimatoprost revealed an elevated risk of conjunctival hyperemia with bimatoprost (RR 1.59, 95% CI, 1.02 to 2.48, P = 0.04, I2 = 76%, 95% CI, 16 to 88, P = 0.002). Conclusion Randomized head-to-head evaluations of prostaglandin therapy demonstrate similar efficacy effects, but differing hyperemia effects. PMID:19684868

  19. 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.

  20. Intraocular pressure-lowering effects of commonly used fixed combination drugs with timolol in the management of primary open angle glaucoma

    PubMed Central

    Ozer, Murat Atabey; Acar, Mutlu; Yildirim, Cem

    2014-01-01

    AIM To evaluate intraocular pressure (IOP)-lowering effect and ocular tolerability of brimonidine/timolol, dorzolamide/timolol and latanoprost/timolol fixed combination therapies in the management of primary open angle glaucoma. METHODS Each drug was administered for two months, after which a circadian tonometric curve was recorded using a Goldmann applanation tonometer. Ocular discomfort (conjunctival hyperemia, burning or stinging, foreign body sensation, itching, ocular pain) of each eye was assessed by the subject on a standardized ocular discomfort scale. RESULTS Among the three study groups, there were no significant differences in the mean baseline IOP measurements, mean 2nd mo IOP measurements, and mean (%) change of IOPs from baseline. Among the three study groups, there were no significant differences in the mean IOP measurements obtained at circadian tonometric curves at baseline and at two months controls. In sum brimonidine/timolol, dorzolamide/timolol and latanoprost/timolol fixed combination therapies showed similar effects on IOP levels. CONCLUSION Brimonidine/timolol, dorzolamide/timolol and latanoprost/timolol fixed combination therapies showed similar lowering efficaties on IOP levels whereas there was no any difference between each other. PMID:25349802

  1. 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. PMID:26752265

  2. 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

  3. Apolipoprotein E–Promoter Single-Nucleotide Polymorphisms Affect the Phenotype of Primary Open-Angle Glaucoma and Demonstrate Interaction with the Myocilin Gene

    PubMed Central

    Copin, Bruno; Brézin, Antoine P.; Valtot, Françoise; Dascotte, Jean-Claude; Béchetoille, Alain; Garchon, Henri-Jean

    2002-01-01

    Primary open-angle glaucoma (POAG) is an optic neuropathy that has a high worldwide prevalence and that shows strong evidence of complex inheritance. The myocilin (MYOC) gene is the only one that has thus far been shown to have mutations in patients with POAG. Apolipoprotein E (APOE) plays an essential role in lipid metabolism, and the APOE gene has been involved in neuronal degeneration that occurs in Alzheimer disease (AD). Here, we report that two APOE-promoter single-nucleotide polymorphisms (SNPs) previously associated with AD also modify the POAG phenotype. APOE(−219G) is associated with increased optic nerve damage, as reflected by increased cup:disk ratio and visual field alteration. In addition, APOE(−491T), interacting at a highly significant level with an SNP in the MYOC promoter, MYOC(−1000G), is associated with increased intraocular pressure (IOP) and with limited effectiveness of IOP-lowering treatments in patients with POAG. Together, these findings establish APOE as a potent modifier for POAG, which could explain the linkage to chromosome 19q previously observed by use of a genome scan for this condition and an increased frequency of glaucoma in patients with AD. The findings also shed new light on potential mechanisms of optic nerve damage and of IOP regulation in POAG. PMID:11992263

  4. Joint Effects of Intraocular Pressure and Myopia on Risk of Primary Open-Angle Glaucoma: The Singapore Epidemiology of Eye Diseases Study

    PubMed Central

    Tham, Yih-Chung; Aung, Tin; Fan, Qiao; Saw, Seang-Mei; Siantar, Rosalynn Grace; Wong, Tien Y.; Cheng, Ching-Yu

    2016-01-01

    We examined the joint effects of intraocular pressure (IOP) and myopia on the risk of primary open angle glaucoma (POAG) in a multi-ethnic Asian population. A total of 9,422 participants (18,469 eyes) in the Singapore Epidemiology of Eye Diseases Study were included. Of them, 213 subjects (273 eyes) had POAG. All participants underwent standardised examinations. The independent and joint effects of IOP and myopia on POAG were examined using logistic regression models. Generalised estimating equation models were used to account for correlation between eyes. Higher IOP, longer axial length, and more negative spherical equivalent were independently associated with POAG, after adjusting for relevant covariates (all P ≤ 0.005). Significant interaction between IOP and myopia on POAG was observed (P interaction = 0.025). Eyes with moderate-to-high myopia (<−3.0 dioptres) with high IOP (≥20 mmHg) were 4.27 times (95% CI, 2.10–8.69) likely to have POAG, compared to eyes without myopia (>−0.5 dioptres) and with IOP <20 mmHg. Eyes with AL of ≥25.5 mm and high IOP (≥20 mmHg) were 16.22 times (95% CI, 7.73 to 34.03) likely to have POAG, compared to eyes with shorter AL (<23.5 mm) and lower IOP (<20 mmHg). These findings may provide additional insights into the pathophysiology of POAG and are particularly relevant for Asian populations. PMID:26758554

  5. BDNF and HSP gene polymorphisms and their influence on the progression of primary open-angle glaucoma in a Polish population

    PubMed Central

    Nowak, Alicja; Szaflik, Jacek P.; Gacek, Mira; Przybylowska-Sygut, Karolina; Kamińska, Anna; Szaflik, Jerzy

    2014-01-01

    Introduction Glaucoma is a neurodegenerative disease that is often associated with high intraocular pressure (IOP). One of the effects of elevated IOP is disorder of neurotrophic molecules transport, including brain-derived neurotrophic factor (BDNF) and recruit specific cellular proteins called “heat shock proteins” (HSPs). The aim of this study was to evaluate a relationship between the BDNF and HSP70-1 gene polymorphisms with risk occurrence of primary open-angle glaucoma (POAG). Material and methods The study consisted of 167 patients with POAG (mean age: 73 ±9) and 193 healthy subjects (mean age: 64 ±13). Genomic DNA was extracted from peripheral blood. Analysis of the gene polymorphisms was performed using PCR-RFLP, using the following restriction enzymes: NlaIII (rs6265) and BsrBI (rs1043618). The Heidelberg retinal tomography (HRT) clinical parameters were also analyzed. The odds ratios (ORs) and 95% confidence intervals (CIs) for each genotype and allele were calculated. Results Comparison of the distributions of genotypes and alleles of the 196G/A polymorphism of the BDNF gene as well as 190G/C polymorphism of the HSP70-1 gene and analysis of the odds ratio (OR) showed no statistically significant differences between POAG patients and controls (p > 0.05). However, there was a statistically significant association of the 196G/A of BDNF and 190G/C of HSP70-1 gene polymorphisms with progression of POAG depending on values of clinical parameters. 196G/A of BDNF correlated with the parameters GDx and RA (p = 0.03; p = 0.002, respectively), while 190G/C of HSP70-1 correlated with c/d and RA (p = 0.014, p = 0.024, respectively). Conclusions The BDNF 196G/A and HSP70-1 190G/C gene polymorphisms may be related to progression of POAG. PMID:25624860

  6. Inducible and Endothelial Nitric Synthetase Expression and Nitrotyrosine Accumulation in Iris Vasculature of Patients with Primary Open-Angle Glaucoma: A Pilot Study

    PubMed Central

    Rokicki, Wojciech; Żaba, Małgorzata; Wyględowska-Promieńska, Dorota; Kabiesz, Adam; Reichman-Warmusz, Edyta; Brzozowa, Marlena; Majewski, Wojciech; Wojnicz, Romuald

    2015-01-01

    Background The “double-faced” effect of nitric oxide (NO) is thought to play an important role in triggering and progression of glaucoma. Material/Methods Iris samples were obtained during iridectomy in 35 patients (mean age of 65.4±5.3 years) with diagnosed primary open-angle glaucoma (POAG). The controls were collected postmortem from 10 donors with a mean age of 62.2±1.9 years. Visual field defects were evaluated by perimetry. The Hodapp-Parrish-Anderson classification was used to divide patients into 3 visual field defect groups. The intraocular pressure was measured 3 times before surgery using applanation tonometry. The phenotype activity of nitric oxide synthase (NOS) isoenzymes (endothelial – eNOS and inducible – iNOS) and expression of nitrotyrosine in iris vasculature was assessed. Results Significant differences were found between glaucoma patients and the controls in eNOS and iNOS activity (Mann-Whitney test, U=35.5, Z=−2.037, p=0.04 and U=21, Z=2.69, p=0.007, respectively). In addition, the results showed an upregulation of nitrotyrosine in the capillary endothelial cells in the study group, which was associated with the duration of diagnosed glaucoma (R-Spearman of 0.33, p=0.0047) and visual field mean defect MD (R-Spearman of 0.29, p=0.019). Moreover, the activity of nitrotyrosine was significantly correlated with iNOS immunoreactivity (R-Spearman of 0.5, p=0.0001). However, the iNOS activity significantly varied among Hodapp-Parrish-Anderson groups (p=0.03). Conclusions Our observations confirmed the association between glaucomatous disturbances and upregulation of iNOS, together with increased nitrotyrosine storage. PMID:25564962

  7. Efficacy and tolerability of mono-compound topical treatments for reduction of intraocular pressure in patients with primary open angle glaucoma or ocular hypertension: an overview of reviews

    PubMed Central

    Daka, Qëndresë; Trkulja, Vladimir

    2014-01-01

    Aim To evaluate the existing evidence on relative efficacy and tolerability of topical mono-compound intraocular pressure (IOP)-lowering drugs in treatment of primary open angle glaucoma (POAG) and ocular hypertension (OHT). Methods In this systematic review of systematic reviews/meta-analyses of randomized controlled trials a thorough and sensitive search of PubMed, Embase and Cochrane Databases was performed. Individual study methodological quality and quality of evidence were assessed using the AMSTAR checklist and the GRADE system, respectively. The relationships between individual drugs were evaluated based on the best available evidence. Results Of the 133 initial non-duplicate records, 16 studies met the inclusion criteria. Five achieved an overall “moderate” (none achieved “high”) quality of evidence and evaluated prostaglandin analogues (PGAs) – latanoprost, travoprost, and bimatoprost; timolol; “other beta-blockers;” carbonic anhydrase inhibitors (CAI) as a group or dorzolamide separately; and brimonidine. “Moderate quality” refers to efficacy and incidence of conjunctival hyperemia. Quality of evidence regarding other tolerability aspects was low. PGAs should be considered equivalent regarding efficacy, but latanoprost was relevantly better tolerated than the other two. Non-PGA compounds did not relevantly differ between each other in either efficacy or safety. Timolol and brimonidine were relevantly less effective than all PGAs. The same was true for CAI vs bimatoprost. Regarding tolerability, timolol was superior to all PGAs and brimonidine and CAI were superior to bimatoprost. Conclusion No high quality evidence on relative efficacy and tolerability of the most commonly used mono-compound IOP-lowering drugs for POAG/OHT exists. Moderate quality evidence indicates latanoprost as a treatment with the most favorable trade-off between benefits and harms. PMID:25358880

  8. 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

  9. Short-Term Reproducibility of Twenty-Four-Hour Intraocular Pressure Curves in Untreated Patients with Primary Open-Angle Glaucoma and Ocular Hypertension

    PubMed Central

    Xu, Shuo; Jiao, Qin; Cheng, Yu; Sun, Jie; Lu, Qiong; Zhong, Yisheng

    2015-01-01

    Purpose To assess the short-term day-to-day reproducibility of 24-hour intraocular pressure (IOP) curves in various respects in untreated primary open-angle glaucoma (POAG) and ocular hypertension (OHT) patients. Methods 47 subjects with POAG and 34 subjects with OHT underwent IOP measurements every 2 hours in both eyes for consecutive 48 hours by a non-contact tonometer (NCT). IOP values at each time point were recorded. Mean IOP, peak IOP, time difference of peak IOP between two days and IOP fluctuation were also calculated. Intraclass correlation coefficients (ICCs) and Bland-Altman plots were used to evaluate reproducibility. Results ICCs of the entire IOP values for a complete 24-hour curve were 0.577 and 0.561 in POAG and OHT patients, respectively. ICCs of IOP values at different time points ranged from 0.384 (10am) to 0.686 (4am) in POAG patients and from 0.347 (6am) to 0.760 (4am) in OHT patients. ICCs of mean IOP, peak IOP and IOP fluctuation were respectively 0.832, 0.704, 0.367 in POAG patients and 0.867, 0.816 0.633 in OHT patients. Only 37.23% and 35.29% of the peak IOP time points appeared within the time difference of 2 hours in POAG and OHT patients, respectively, while 53.19% and 48.53% appeared within 4 hours in POAG and OHT patients, respectively. Conclusion A 24-hour IOP curve in a single day is not highly reproducible in short-term and has limited use for evaluating individual IOP condition. Mean IOP and peak IOP for a 24-hour IOP curve are useful parameters in clinical follow-up, while IOP value at a certain time point, IOP fluctuation and peak IOP time point should be interpreted with caution. PMID:26466325

  10. An observational study of bimatoprost 0.01% in treatment-naïve patients with primary open angle glaucoma or ocular hypertension: the CLEAR trial

    PubMed Central

    Nixon, Donald R; Simonyi, Susan; Bhogal, Meetu; Sigouin, Christopher S; Crichton, Andrew C; Discepola, Marino; Hutnik, Cindy ML; Yan, David B

    2012-01-01

    Background This study was designed to evaluate the occurrence and severity of ocular hyperemia in subjects with elevated intraocular pressure (IOP) due to primary open angle glaucoma (POAG) or ocular hypertension (OHT) following treatment with bimatoprost 0.01% in a real-world clinical setting. Methods This was an open-label, observational study conducted at 67 centers in Canada. Subjects with elevated IOP due to POAG or OHT instilled bimatoprost 0.01% topically as monotherapy once daily. Ocular hyperemia was graded by the investigator at baseline and weeks 6 and 12 using a photographic five-point grading scale. Change in IOP from baseline was also evaluated at these time points. This analysis includes only the subgroup of 522 subjects who were naïve to IOP-lowering medication prior to the study. Results After 12 weeks of treatment with bimatoprost 0.01%, hyperemia was graded as none-to-mild (grades 0, +0.5, or +1) for 93.3% of subjects and as moderate-to-severe (grades +2 or +3) for 6.7%. At weeks 6 and 12, most subjects (93.2% and 93.5%) had no change in hyperemia grade from baseline. IOP was reduced by 7.4 mmHg (29.8%) at week 6 and 7.7 mmHg (30.9%) at week 12 from baseline. Conclusion This real-world, observational study found that bimatoprost 0.01% instilled once daily reduced IOP by a mean of 30% from baseline without moderate or severe ocular hyperemia in 93% of treatment-naïve subjects with POAG or OHT. PMID:23269858

  11. Influence of BAK-Preserved Prostaglandin Analog Treatment on the Ocular Surface Health in Patients with Newly Diagnosed Primary Open-Angle Glaucoma

    PubMed Central

    Tomić, Martina; Kaštelan, Snježana; Metež Soldo, Kata; Salopek-Rabatić, Jasminka

    2013-01-01

    Purpose. Primary open-angle glaucoma (POAG), a chronic, degenerative optic neuropathy, requires persistent decrease of intraocular pressure so as to prevent visual impairment and blindness. However, long-term use of topical ocular medications may affect ocular surface health. Purpose of this study was to evaluate the influence of BAK-preserved prostaglandin analog treatment on the ocular surface health in patients with newly diagnosed POAG. Methods. 40 newly diagnosed POAG patients were included in this prospective study. Intraocular pressure (IOP), tear break-up time (TBUT), and ocular surface disease index (OSDI) were assessed at baseline and 3-month after starting treatment with BAK-preserved travoprost 0.004%. Results. IOP decreased in all patients from baseline to 3-month final visit (23.80 ± 1.73 mmHg versus 16.78 ± 1.27 mmHg; P < 0.001). Mean TBUT decreased from 11.70 ± 1.86 seconds at baseline to 8.30 ± 1.29 seconds at 3-month final visit (<0.001). Mean OSDI score increased from 31.63 ± 18.48 to 44.41 ± 16.48 (P < 0.001). Conclusions. This study showed that BAK-preserved travoprost 0.004% is an effective medication in newly diagnosed POAG patients, but its long-term use may negatively influence ocular surface health by disrupting the tear film stability. Further studies are needed to better understand the clinical effects of different preservative types and concentrations on the ocular surface. PMID:23971041

  12. Joint Effects of Intraocular Pressure and Myopia on Risk of Primary Open-Angle Glaucoma: The Singapore Epidemiology of Eye Diseases Study.

    PubMed

    Tham, Yih-Chung; Aung, Tin; Fan, Qiao; Saw, Seang-Mei; Siantar, Rosalynn Grace; Wong, Tien Y; Cheng, Ching-Yu

    2016-01-01

    We examined the joint effects of intraocular pressure (IOP) and myopia on the risk of primary open angle glaucoma (POAG) in a multi-ethnic Asian population. A total of 9,422 participants (18,469 eyes) in the Singapore Epidemiology of Eye Diseases Study were included. Of them, 213 subjects (273 eyes) had POAG. All participants underwent standardised examinations. The independent and joint effects of IOP and myopia on POAG were examined using logistic regression models. Generalised estimating equation models were used to account for correlation between eyes. Higher IOP, longer axial length, and more negative spherical equivalent were independently associated with POAG, after adjusting for relevant covariates (all P ≤ 0.005). Significant interaction between IOP and myopia on POAG was observed (P interaction = 0.025). Eyes with moderate-to-high myopia (<-3.0 dioptres) with high IOP (≥20 mmHg) were 4.27 times (95% CI, 2.10-8.69) likely to have POAG, compared to eyes without myopia (>-0.5 dioptres) and with IOP <20 mmHg. Eyes with AL of ≥25.5 mm and high IOP (≥20 mmHg) were 16.22 times (95% CI, 7.73 to 34.03) likely to have POAG, compared to eyes with shorter AL (<23.5 mm) and lower IOP (<20 mmHg). These findings may provide additional insights into the pathophysiology of POAG and are particularly relevant for Asian populations. PMID:26758554

  13. 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

  14. No Association between CagA- and VacA-Positive Strains of Helicobacter pylori and Primary Open-Angle Glaucoma: A Case–Control Study

    PubMed Central

    Noche, C. Domngang; Njajou, O.; Etoa, F. X.

    2016-01-01

    INTRODUCTION Glaucoma is a public health issue worldwide, particularly in Africa. In Cameroon, the prevalence rate of primary open-angle glaucoma (POAG) ranges between 4.5% and 8.2%. Helicobacter pylori (HP) has been implicated in digestive and extra-digestive diseases, including glaucoma. The objective of this work was to evaluate the implication of CagA- and VacA-positive strains of HP in POAG using a case–control design. METHODS An analytical study was conducted from October 2013 to December 2013. Participants were recruited in eye care centers in Yaoundé. Enzyme-linked immunosorbent assays (ELISAs) were carried out in the La Grace Laboratory in Yaoundé. RESULTS The total sample consisted of 50 POAG patients and 31 controls with a mean age of 58.5 ± 12.2 years and 45.5 ± 14.6 years, respectively. The prevalence rates of HP in the POAG and control groups were 74% (37/50) and 87% (27/31), respectively (P = 0.125). The prevalence rates of CagA-positive HP seropositivity in the POAG and control groups were 26% and 22.58%, respectively (P = 0.47), and the prevalence rates of VacA-positive HP participants were 6% and 0%, respectively (P = 0.22). CONCLUSION The HP prevalence rates among POAG patients and controls were 74% and 87%, respectively. There was no significant difference between prevalence rates of HP in the POAG and control groups. There was no association between POAG and CagA- or VacA-positive HP infection. PMID:26917977

  15. Intraeye retinal nerve fiber layer and macular thickness asymmetry measurements for the discrimination of primary open-angle glaucoma and normal tension glaucoma

    PubMed Central

    Khanal, Safal; Davey, Pinakin Gunvant; Racette, Lyne; Thapa, Madhu

    2015-01-01

    Purpose The aim of this study was to evaluate the diagnostic capability of intraeye retinal nerve fiber layer (RNFL) thickness and macular thickness (MT) asymmetry measurements for the discrimination of normal tension glaucoma (NTG) and primary open-angle glaucoma (POAG) using spectral domain optical coherence tomography (SD-OCT). Methods A total of 90 subjects were enrolled including 30 consecutive healthy subjects, 30 consecutive subjects with POAG, and 30 consecutive subjects with NTG. RNFL thicknesses around the optic disc as well as MT measurements were taken with circular and radial SD-OCT scans. Intraeye retinal and MT asymmetry were calculated as the absolute difference between superior and inferior hemispheres of the eye using posterior pole asymmetry analysis protocol. Analysis of variance was used for comparison and areas under the receiver operating characteristic (AROC) were obtained for different parameters among the three diagnostic groups. Results There was a significant difference in MT asymmetry for all comparison groups (normal-NTG, p < 0.05; normal-POAG, p < 0.001; and NTG-POAG, p < 0.001). Intraeye retinal nerve fiber thickness asymmetry measurements were not different between the groups (normal-NTG, p < 0.187; normal-POAG, p < 0.056; and NTG-POAG, p < 0.837). The area under ROC curves exceeded 0.800 for all the studied parameters, including the MT asymmetry except for intraeye RNFL thickness asymmetry which had the lowest AROC as well as the least sensitivity for identifying subjects with NTG from normal (AROC = 0.626, sensitivity = 30%); POAG from normal (AROC = 0.644, sensitivity = 37%) and NTG from POAG (AROC = 0.533, sensitivity = 13%). Conclusion The intraeye MT asymmetry holds significant potential as a distinguishing parameter for NTG and POAG. PMID:26652244

  16. Associations of polymorphisms of LOXL1 gene with primary open-angle glaucoma: a meta-analysis based on 5,293 subjects

    PubMed Central

    Wu, Mingyu; Zhu, Xiao-Yan

    2015-01-01

    Objective Previous studies indicated that the relationship between lysyl oxidase-like 1 (LOXL1) gene polymorphisms and primary open-angle glaucoma (POAG) remains inconsistent. In the present study, we aimed to perform a meta-analysis to investigate the association of LOXL1 polymorphisms with POAG risk. Methods Literatures were electronically searched in the PubMed, EMBASE, CNKI, Wanfang, and VIP databases. The published literatures, which are case-control or cohort studies on the relationship between the polymorphisms (rs1048661, rs3825942, rs2165241) of the LOXL1 gene and POAG, were documented. Results We included 13 literatures including 5,293 subjects for the present study. A meta-analysis showed that the risk of POAG in individuals carrying the C allele of rs2165241 was 1.26 times higher compared with those carrying the T allele (odds ratio (OR) = 1.26, 95% confidence interval (CI): 1.09 ~1.46) in the total population. In the Caucasian population, we also found that individuals carrying the C allele of rs2165241 have an increased risk for POAG compared to those subjects carrying the T allele (OR = 1.42, 95% CI: 1.19 ~1.69, p = 0.0001). In addition, we found that the rs1048661 polymorphism was associated with POAG in the Asian population (OR = 1.17, 95% CI: 1.02 ~1.35, p = 0.03), and rs3825942 was associated with POAG in the Caucasian population (OR = 2.69, 95% CI: 1.61 ~4.47, p<0.001). Conclusions The polymorphisms of the LOXL1 gene were associated with the susceptibility of POAG. PMID:25750511

  17. Two Independent Mutations in ADAMTS17 Are Associated with Primary Open Angle Glaucoma in the Basset Hound and Basset Fauve de Bretagne Breeds of Dog

    PubMed Central

    Oliver, James A. C.; Forman, Oliver P.; Pettitt, Louise; Mellersh, Cathryn S.

    2015-01-01

    Purpose Mutations in ADAMTS10 (CFA20) have previously been associated with primary open angle glaucoma (POAG) in the Beagle and Norwegian Elkhound. The closely related gene, ADAMTS17, has also been associated with several different ocular phenotypes in multiple breeds of dog, including primary lens luxation and POAG. We investigated ADAMTS17 as a candidate gene for POAG in the Basset Hound and Basset Fauve de Bretagne dog breeds. Methods We performed ADAMTS17 exon resequencing in three Basset Hounds and three Basset Fauve de Bretagne dogs with POAG. Identified variants were genotyped in additional sample cohorts of both breeds and dogs of other breeds to confirm their association with disease. Results All affected Basset Hounds were homozygous for a 19 bp deletion in exon 2 that alters the reading frame and is predicted to lead to a truncated protein. Fifty clinically unaffected Basset Hounds were genotyped for this mutation and all were either heterozygous or homozygous for the wild type allele. Genotyping of 223 Basset Hounds recruited for a different study revealed a mutation frequency of 0.081 and predicted frequency of affected dogs in the population to be 0.007. Based on the entire genotyping dataset the association statistic for the POAG-associated deletion was p = 1.26 x 10−10. All affected Basset Fauve de Bretagne dogs were homozygous for a missense mutation in exon 11 causing a glycine to serine amino acid substitution (G519S) in the disintegrin-like domain of ADAMTS17 which is predicted to alter protein function. Unaffected Basset Fauve de Bretagne dogs were either heterozygous for the mutation (5/24) or homozygous for the wild type allele (19/24). Based on the entire genotyping dataset the association statistic for the POAG-associated deletion was p = 2.80 x 10−7. Genotyping of 85 dogs of unrelated breeds and 90 dogs of related breeds for this variant was negative. Conclusion This report documents strong associations between two independent ADAMTS17

  18. 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

  19. Five-Year Incidence of Primary Open-Angle Glaucoma and Rate of Progression in Health Center-Based Korean Population: The Gangnam Eye Study

    PubMed Central

    Jeoung, Jin Wook; Park, Ki Ho; Kim, Dong Myung

    2014-01-01

    Objective To investigate the 5-year incidence and progression rate of primary open-angle glaucoma (POAG) in a health-center-based Korean population. Methods The study population comprised 5,021 subjects who participated in standardized health screening (including non-contact tonometry and fundus photography) at the Gangnam Healthcare Center during the period from January 2005 to December 2006 and again from January 2010 to December 2011. Among these subjects, 948 (18.9%) with findings suggestive of glaucoma were subjected to a comprehensive glaucoma evaluation, which included applanation tonometry and standard automated perimetry. Based on the results, the subjects were diagnosed as POAG suspect or definite POAG. Results The 5-year incidences of POAG suspect and definite POAG were 0.84% (42 subjects) and 0.72% (36 subjects), respectively. The rate of progression from POAG suspect to definite POAG was 4.75% per year. In subjects with a baseline intraocular pressure (IOP) >21 mmHg, the incidence of POAG suspect or definite POAG was significantly higher than in those with a baseline IOP≤21 mmHg (32% vs. 1.05%; P<0.001). A multivariate analysis showed that the progression from POAG suspect to definite POAG was significantly associated with older age (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.03–1.10), higher baseline IOP (OR, 1.10; 95% CI, 1.01–1.24), higher body mass index (BMI) (OR, 1.15; 95% CI, 1.03–1.31), higher education level (OR, 1.57; 95% CI, 1.05–2.17), and higher hematocrit level (OR, 1.22; 95% CI, 1.08–1.43). Conclusions In the health-center-based Korean population, the 5-year incidence of POAG was 0.72%, and the rate of progression from POAG suspect to definite POAG was 4.75% per year. This study identified old age, high baseline IOP, high BMI, high level of education, and high hematocrit level as significant risk factors for incident POAG. PMID:25474589

  20. Fixed combination of latanoprost and timolol vs the individual components for primary open angle glaucoma and ocular hypertension: a systematic review and meta-analysis

    PubMed Central

    Xing, Yi; Jiang, Fa-Gang; Li, Teng

    2014-01-01

    AIM To assess the effects of the fixed combination of 0.005% latanoprost and 0.5% timolol (FCLT) vs their individual components for primary open angle glaucoma (POAG) and ocular hypertension (OHT). METHODS After searched PubMed, EMBASE, the Cochrane Library and SCI, all randomized controlled clinical trials (RCTs) and cross-over studies were included. The control groups were the mono therapy or the concomitant therapy of latanoprost and timolol. The outcomes were visual field defect, optic atrophy, mean intraocular pressure (IOP) and IOP fluctuation. The analysis was carried out in RevMan version 5.1 software. RESULTS The post-intervention mean IOP of FCLT was significantly lower compared to timolol [mean difference (MD) -2.92, 95%CI -3.28 to -2.55, P<0.00001] and latanoprost (MD -1.11, 95%CI -1.51 to -0.72, P<0.00001). The post-intervention IOP fluctuation was also significantly lower compared to timolol (MD -0.88, 95%CI -1.23 to -0.53, P<0.00001) and latanoprost (MD -0.63, 95%CI -1.04 to -0.22, P=0.002). The mean IOP was higher in FCLT morning dose group than the one in unfixed combination of 0.005% latanoprost and 0.5% timolol (UFCLT) (MD 1.10, 95%CI 0.81 to 1.39, P<0.00001). Otherwise, there was no difference between FCLT evening dose group and UFCLT (MD 0.34, 95% CI -0.01 to 0.69, P=0.06). There was no statistical difference for the incidence of visual field defect and optic atrophy between FCLT and the monotherapy of components. CONCLUSION A better IOP lowering effect has been demonstrated for FCLT compared to the mono therapy of components. The IOP lowering effect was worse for FCLT morning dose and almost same for FCLT evening dose compared to the UFCLT. We need more long-term high quality RCTs to demonstrate the outcomes of visual field defect and optic atrophy. PMID:25349811

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

    PubMed

    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

  2. Schlemm’s Canal and Trabecular Meshwork in Eyes with Primary Open Angle Glaucoma: A Comparative Study Using High-Frequency Ultrasound Biomicroscopy

    PubMed Central

    Yan, Xiaoqin; Li, Mu; Chen, Zhiqi; Zhu, Ying; Song, Yinwei; Zhang, Hong

    2016-01-01

    We investigated in vivo changes in Schlemm’s canal and the trabecular meshwork in eyes with primary open angle glaucoma (POAG). Relationships between Schlemm’s canal diameter, trabecular meshwork thickness, and intraocular pressure (IOP) were examined. Forty POAG patients and 40 normal individuals underwent 80-MHz Ultrasound Biomicroscopy examinations. The Schlemm’s canal and trabecular meshwork were imaged in superior, inferior, nasal and temporal regions. Normal individuals had an observable Schlemm’s canal in 80.3% of sections, a meridional canal diameter of 233.0±34.5 μm, a coronal diameter of 44.5±12.6 μm and a trabecular meshwork thickness of 103.9±11.1 μm, in POAG patients, Schlemm’s canal was observable in 53.1% of sections, a meridional canal diameter of 195.6±31.3 μm, a coronal diameter of 35.7±8.0 μm, and a trabecular meshwork thickness of 88.3±13.2 μm, which significantly differed from normal (both p <0.001). Coronal canal diameter (r = -0.623, p < 0.001) and trabecular meshwork thickness (r = -0.663, p < 0.001) were negatively correlated with IOP, but meridional canal diameter was not (r = -0.160, p = 0.156). Schlemm’s canal was observable in 50.5% and 56.6% of POAG patients with normal (<21 mmHg) and elevated (>21 mmHg) IOP, respectively (χ = 1.159, p = 0.282). Coronal canal diameter was significantly lower in the elevated IOP group (32.6±4.9 μm) than in the normal IOP group (35.7±8.0 μm, p < 0.001). This was also true of trabecular meshwork thickness (81.9±10.0 μm vs. 97.1±12.0 μm, p < 0.001). In conclusion, eyes with POAG had fewer sections with an observable Schlemm’s canal. Canal diameter and trabecular meshwork thickness were also lower than normal in POAG patients. Schlemm’s canal coronal diameter and trabecular meshwork thickness were negatively correlated with IOP. PMID:26726880

  3. Schlemm's Canal and Trabecular Meshwork in Eyes with Primary Open Angle Glaucoma: A Comparative Study Using High-Frequency Ultrasound Biomicroscopy.

    PubMed

    Yan, Xiaoqin; Li, Mu; Chen, Zhiqi; Zhu, Ying; Song, Yinwei; Zhang, Hong

    2016-01-01

    We investigated in vivo changes in Schlemm's canal and the trabecular meshwork in eyes with primary open angle glaucoma (POAG). Relationships between Schlemm's canal diameter, trabecular meshwork thickness, and intraocular pressure (IOP) were examined. Forty POAG patients and 40 normal individuals underwent 80-MHz Ultrasound Biomicroscopy examinations. The Schlemm's canal and trabecular meshwork were imaged in superior, inferior, nasal and temporal regions. Normal individuals had an observable Schlemm's canal in 80.3% of sections, a meridional canal diameter of 233.0±34.5 μm, a coronal diameter of 44.5±12.6 μm and a trabecular meshwork thickness of 103.9±11.1 μm, in POAG patients, Schlemm's canal was observable in 53.1% of sections, a meridional canal diameter of 195.6±31.3 μm, a coronal diameter of 35.7±8.0 μm, and a trabecular meshwork thickness of 88.3±13.2 μm, which significantly differed from normal (both p <0.001). Coronal canal diameter (r = -0.623, p < 0.001) and trabecular meshwork thickness (r = -0.663, p < 0.001) were negatively correlated with IOP, but meridional canal diameter was not (r = -0.160, p = 0.156). Schlemm's canal was observable in 50.5% and 56.6% of POAG patients with normal (<21 mmHg) and elevated (>21 mmHg) IOP, respectively (χ = 1.159, p = 0.282). Coronal canal diameter was significantly lower in the elevated IOP group (32.6±4.9 μm) than in the normal IOP group (35.7±8.0 μm, p < 0.001). This was also true of trabecular meshwork thickness (81.9±10.0 μm vs. 97.1±12.0 μm, p < 0.001). In conclusion, eyes with POAG had fewer sections with an observable Schlemm's canal. Canal diameter and trabecular meshwork thickness were also lower than normal in POAG patients. Schlemm's canal coronal diameter and trabecular meshwork thickness were negatively correlated with IOP. PMID:26726880

  4. [Screening in open angle glaucoma].

    PubMed

    Mocanu, Carmen; Mocanu, Andrei

    2012-01-01

    Primary open angle glaucoma (POAG) represents the second cause of mondial cecity, after retinal diabetes complications, with extremely severe implications in quality of life. Screening testing for glaucoma is justified, because only the diagnosis in very incipient stage will preserve the visual function; any treatment will not assure the reversibility of pre-existent optic nerve lesions. Screening of glaucoma, will take into a consideration the costs, the time of investigation, the adverse effects, and the sensitivity and specificity of tests; the last parameter also will strongly influence the positive predictive value. An ideal screening identifies all subjects that present the disease (sensitivity) and will exclude all healthy subjects (specificity). In this moment, in Dolj district, the diagnosis is based on active diagnosis of new cases of glaucoma on the high risk level population, therefore in a 210000 habitants. 4723 patients with glaucoma are diagnosed, screened and follow-up on medical cabinets and on Center of Glaucoma, which coordinates their activity. To better monitored patients, automatized programs with acquisition and storage for different types of medical imaging facilities had become indispensable to any routine practice. PMID:23755511

  5. 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.

  6. A combined analysis of five observational studies evaluating the efficacy and tolerability of bimatoprost/timolol fixed combination in patients with primary open-angle glaucoma or ocular hypertension

    PubMed Central

    Pfennigsdorf, Stefan; de Jong, Leo; Makk, Stefan; Fournichot, Yvette; Bron, Alain; Morgan-Warren, Robert J; Maltman, John

    2013-01-01

    Objective The aim of this study was to evaluate the safety and efficacy of a fixed combination of bimatoprost 0.03% and timolol (BTFC) in a clinical setting, in a large sample of patients with primary open-angle glaucoma or ocular hypertension and insufficient intraocular pressure (IOP) lowering on prior therapy. Methods Patient data were combined (n = 5556) from five multicenter, observational, non-controlled, open-label studies throughout Europe. Patients were identified from 830 sites in Austria, France, Germany, The Netherlands, and Switzerland. Assessments were made at baseline, 6 weeks (in Austrian, German and Swiss centers), and 12 weeks in all centers. Results BTFC lowered mean IOP from baseline by 5.4 mmHg over the 12-week duration of the studies (P < 0.0001). At study entry, 92.9% of patients were receiving another ocular hypotensive medication. In patients with no previous treatment (n = 311), BTFC reduced IOP by −9.1 mmHg, corresponding to a reduction from baseline of 36.4% (P < 0.0001). In patients receiving prior therapy of a prostaglandin analog, a β-blocker, or a fixed combination, BTFC reduced IOP by a further 24.5%, 25.9%, and 21.4%, respectively. The majority of patients (90.3%) reported no adverse events. The most common adverse events were conjunctival hyperemia (3.2%) and eye irritation (2.8%). BTFC was rated as “good” or “very good” by 92.5% of physicians and 88.0% of patients. Most patients (96.3%) were equally or more compliant with BTFC than with their previous treatment. Conclusion In routine clinical practice, BTFC achieved consistent IOP lowering in both previously treated and untreated patients with primary open-angle glaucoma or ocular hypertension. BTFC was associated with significant IOP reductions, good tolerability, and good compliance. PMID:23814459

  7. Chronic open-angle glaucoma

    PubMed Central

    Adatia, Feisal A.; Damji, Karim F.

    2005-01-01

    INTRODUCTION Chronic open-angle glaucoma (COAG) is a leading cause of irreversible blindness worldwide, including in Canada. It presents a challenge in diagnosis, as disease often progresses without symptoms; an estimated 50% of cases are undetected. SOURCES OF INFORMATION MEDLINE searches, reference lists of articles, and expert knowledge from one of the authors (K.F.D.), a glaucoma specialist, were used. MAIN MESSAGE A casefinding approach using early referral to optometrists and ophthalmologists for early detection of COAG is helpful for patients with risk factors such as age above 50, a positive family history, black race, and myopia. Moderate evidence for referral also exists for the following risk factors: hypertension, type 2 diabetes mellitus, hypothyroidism, and sleep apnea. Treatment with intraocular pressure–lowering medication can arrest or slow the course of the disease, permitting patients to retain good visual function. Family physicians should be aware that some intraocular pressure–lowering medications, particularly topical beta-blockers, can pose iatrogenic harm to patients and result in or exacerbate such conditions as asthma, cardiovascular disturbances, depression, and sexual dysfunction. CONCLUSION Appropriate referral patterns and an understanding of common as well as serious side effects of glaucoma medications are important in optimizing management of patients at risk of developing, or who have, COAG. PMID:16190176

  8. A combined analysis of four observational studies evaluating the intraocular pressure-lowering ability and tolerability of bimatoprost 0.01% in patients with primary open-angle glaucoma or ocular hypertension

    PubMed Central

    Stevens, Annemie; Iliev, Milko E; de Jong, Leo; Grobeiu, Ioana; Hommer, Anton

    2016-01-01

    Objective Combine and evaluate data from four clinical practice studies investigating the intraocular pressure (IOP)-lowering ability, tolerability of and patient adherence to bimatoprost 0.01% therapy in patients with primary open-angle glaucoma or ocular hypertension. Methods Data were combined from four multicenter, prospective, observational studies. Patients (n=2,593) were recruited from 328 sites in Austria, Belgium, Switzerland, and the Netherlands. Assessments were at study entry (baseline) and after 10–14 weeks. Results Bimatoprost 0.01% lowered mean IOP by 5.0 mmHg from baseline to final visit (P<0.0001). Individual IOP goals were achieved in 75.5% of patients. Results were similar in right and left eyes; right-eye data are presented here for brevity. The greatest mean IOP reduction was 6.7±4.7 mmHg (28.8% reduction from baseline to final visit, P<0.0001) in treatment-naïve patients. Switching to bimatoprost 0.01% monotherapy from previous monotherapy reduced mean IOP by a further 3.2±3.6 mmHg (17.2%, P<0.0001). Switching to bimatoprost 0.01% from previous prostaglandin monotherapy reduced mean IOP by 2.9±3.5 mmHg (15.5%), including by 3.1±3.4 mmHg (15.8%) and 3.3±4.1 mmHg (16.9%) for previous latanoprost and travoprost treatment, respectively (all P<0.0001). IOP reduction in patients previously treated with a fixed combination was 2.7±4.0 mmHg (14.2%, P<0.0001). The most commonly reported adverse events were conjunctival hyperemia (5.2%) and eye irritation (4.7%). Tolerability was rated as “very good” or “good” by 90.1% of patients. Adherence was rated by physicians as “better than” or “equal to” previous treatment in 97.2% of patients. Conclusion The combined studies demonstrated in a clinical practice setting, bimatoprost 0.01% lowered IOP effectively in treatment-naïve and previously treated ocular hypertension and primary open-angle glaucoma patients, and was associated with good tolerability and patient adherence over 12

  9. Toward Novel Diagnostics for Primary Open-Angle Glaucoma? An Association Study of Polymorphic Variation in Ras Homolog Family Member (A, B, C, D) Genes RHOA, RHOB, RHOC, and RHOD.

    PubMed

    Saracaloglu, Ahmet; Demiryürek, Seniz; Okumus, Seydi; Oztuzcu, Serdar; Bozgeyik, Ibrahim; Coskun, Erol; Aksoy, Umit; Kaydu, Erdal; Erbagci, Ibrahim; Gürler, Bulent; Alasehirli, Belgin; Demiryürek, Abdullah T

    2016-05-01

    The annual economic burden of visual disorders in the United States was estimated as $139 billion. The World Health Organization has listed glaucoma in the top 10 priority eye diseases. Primary open-angle glaucoma (POAG) is a common subtype, with a lack of clinical tools for early diagnosis. The Rho GTPases belong to the Ras superfamily of proteins; the RhoA immunostaining in the optic nerve head in human glaucoma is reportedly increased. We investigated the association of polymorphisms in the Ras Homolog Family Member A, B, C, and D genes (RHOA, RHOB, RHOC, and RHOD, respectively). In a total sample of 361 unrelated subjects (179 patients with POAG and 182 age- and sex-matched healthy controls), RHOA (rs6784820, rs974495), RHOB (rs62121967), RHOC (rs11102522), and RHOD (rs61891303, rs2282502) polymorphisms were characterized by the BioMark HD dynamic array system with real-time polymerarse chain reaction. Among these candidate genetic markers and considering the Bonferroni correction, RHOA rs974495 polymorphism was significantly associated with POAG (p = 0.0011), with the TT genotype increasing the disease risk 4.9 times (95% CI 1.630-15.023). The allele and haplotype distributions of the above RHO candidate polymorphisms did not diplay a significant association. This is the first study, to the best of our knowledge, to identify a significant genotypic association between POAG and RHOA gene rs974495 polymorphism. These observations warrant replication in independent samples in the pursuit of precision medicine for rapid and early glaucoma diagnosis, and molecular targets for innovation in therapeutics of this common eye disease. PMID:27195967

  10. Comparison of diagnostic capability of macular ganglion cell complex and retinal nerve fiber layer among primary open angle glaucoma, ocular hypertension, and normal population using Fourier-domain optical coherence tomography and determining their functional correlation in Indian population

    PubMed Central

    Barua, Nabanita; Sitaraman, Chitra; Goel, Sonu; Chakraborti, Chandana; Mukherjee, Sonai; Parashar, Hemandra

    2016-01-01

    Context: Analysis of diagnostic ability of macular ganglionic cell complex and retinal nerve fiber layer (RNFL) in glaucoma. Aim: To correlate functional and structural parameters and comparing predictive value of each of the structural parameters using Fourier-domain (FD) optical coherence tomography (OCT) among primary open angle glaucoma (POAG) and ocular hypertension (OHT) versus normal population. Setting and Design: Single centric, cross-sectional study done in 234 eyes. Materials and Methods: Patients were enrolled in three groups: POAG, ocular hypertensive and normal (40 patients in each group). After comprehensive ophthalmological examination, patients underwent standard automated perimetry and FD-OCT scan in optic nerve head and ganglion cell mode. The relationship was assessed by correlating ganglion cell complex (GCC) parameters with mean deviation. Results were compared with RNFL parameters. Statistical Analysis: Data were analyzed with SPSS, analysis of variance, t-test, Pearson's coefficient, and receiver operating curve. Results: All parameters showed strong correlation with visual field (P < 0.001). Inferior GCC had highest area under curve (AUC) for detecting glaucoma (0.827) in POAG from normal population. However, the difference was not statistically significant (P > 0.5) when compared with other parameters. None of the parameters showed significant diagnostic capability to detect OHT from normal population. In diagnosing early glaucoma from OHT and normal population, only inferior GCC had statistically significant AUC value (0.715). Conclusion: In this study, GCC and RNFL parameters showed equal predictive capability in perimetric versus normal group. In early stage, inferior GCC was the best parameter. In OHT population, single day cross-sectional imaging was not valuable. PMID:27221682

  11. The additive effect of dorzolamide hydrochloride (Trusopt) and a morning dose of bimatoprost (Lumigan) on intraocular pressure and retrobulbar blood flow in patients with primary open-angle glaucoma

    PubMed Central

    Stankiewicz, Andrzej; Siemiątkowska, Anna; Fuksińska, Beata; Robaszkiewicz, Jacek; Zegadło, Arkadiusz; Ehrlich, Rita; Siesky, Brent; Harris, Alon

    2010-01-01

    Aims To assess the additive effect of dorzolamide hydrochloride 2% on the diurnal intraocular pressure (IOP) curve and retrobulbar haemodynamics in patients with primary open-angle glaucoma (POAG) treated with morning-dosed bimatoprost 0.03%. Methods Twenty-five patients with POAG were evaluated in a prospective, single-masked study. After a 1 week run-in period with bimatoprost all patients were treated with bimatoprost dosed once in the morning for 1 month, after which dorzolamide was added twice daily for 2 months. Goldmann applanation IOP, arterial blood pressure (ABP) and heart rate were measured every 2 h for 24 h and diurnal ocular perfusion pressure (OPP) was calculated. Colour Doppler imaging (CDI) of the ophthalmic artery (OA) and the central retinal artery (CRA) was recorded five times daily. All measurements were taken after the two phases of treatment and were compared. Results The mean baseline IOP was 14.8±3.5 mm Hg. Mean IOP following bimatoprost monotherapy (12.8±2.9 mm Hg) and after 2 months of dorzolamide adjunctive therapy (12.2±2.6 mm Hg) were not statistically significantly different (p=0.544). Only at the 4:00 h time point was IOP significantly reduced using the bimatoprost/dorzolamide combined treatment (p=0.013). The 24 h IOP fluctuations were lower when dorzolamide was added (6.0±2.3 mm Hg vs 4.6±1.5 mm Hg, p=0.0016). Repeated analysis of variance detected a significant decrease of vascular resistance in the OA (p=0.0167) with adjunctive dorzolamide treatment. Conclusions The addition of dorzolamide to morning-dosed bimatoprost had an additive hypotensive effect only on the night-time IOP curve at 4:00 h and resulted in a lower IOP fluctuation. Dorzolamide added to bimatoprost may reduce vascular resistance in the OA. PMID:20558428

  12. A pharmacoeconomic analysis to determine the relative cost-effectiveness of bimatoprost 0.03% eye drops and brimonidine 0.2% eye drops in patients of primary open-angle glaucoma/ocular hypertension

    PubMed Central

    Natt, Navreet Kaur; Gupta, A; Singh, G; Singh, T

    2014-01-01

    Aims: The aim was to compare efficacy and cost-effectiveness of bimatoprost 0.03% and brimonidine 0.2% in primary open-angle glaucoma (POAG)/ocular hypertension (OHT). Settings and Design: Open, randomized, cross-over, comparative study. Materials and Methods: Forty patients of POAG or OHT with intraocular pressure (IOP) <30 mm Hg were included in the study after a written informed consent. The patients were divided randomly into two groups of 20 patients each. Patients of group A were administered bimatoprost 0.03% eye drops once daily, and those of group B brimonidine 0.2% eye drops twice daily for a period of 4 weeks. After a washout period of 4 weeks, the patients were crossed over that is, group A was administered brimonidine 0.2% and group B bimatoprost 0.03%. Fall in IOP at 4 weeks was recorded. The daily cost of each drug was calculated by maximum retail price and the average number of drops per bottle. The cost-effectiveness was then calculated as the cost of drug/mm Hg fall in IOP. Statistics: Independent samples t-test was used to compare the efficacy of both drugs. Results: IOP lowering with bimatoprost (8.9 ± 1.598 mm Hg) was significantly (P < 0.0001) higher than brimonidine (6.55 ± 1.26 mm Hg). The number of drops/ml were 33.43 ± 0.52 and 25.49 ± 0.26, respectively, for bimatoprost and brimonidine. Treatment with bimatoprost was costlier than brimonidine with daily costs/eye Rs. 4.02 ± 0.06 and 3.14 ± 0.03, yearly costs/eye Rs. 1467.46 ± 20.74 and 1147.75 ± 11.15, respectively. Bimatoprost was more cost-effective than brimonidine with the cost-effectiveness ratio (CER) respectively Rs. 13.10 ± 2.61/mm Hg and Rs. 13.96 ± 2.86/mm Hg. Incremental CER Rs. 10.43/mm Hg implies lower costs/mm Hg extra IOP lowering by bimatoprost than Rs. 13.96 for brimonidine. Conclusion: In spite of being costlier, bimatoprost is more efficacious and cost-effective than brimonidine. PMID:25579357

  13. Biomarkers and special features of oxidative stress in the anterior segment of the eye linked to lens cataract and the trabecular meshwork injury in primary open-angle glaucoma: challenges of dual combination therapy with N-acetylcarnosine lubricant eye drops and oral formulation of nonhydrolyzed carnosine.

    PubMed

    Babizhayev, Mark A

    2012-02-01

    The implication of oxidative stress associated with increased oxidant production in mammalian and human cells characterized by the release of free radicals, resulting in cellular degeneration, is involved in many ocular diseases, such as age-related macular degeneration, retinopathy of prematurity, retinal light damage, primary open-angle glaucoma (POAG), and cataract. Cataract is the leading cause of blindness, accounting for 50% of blindness worldwide. Glaucoma, the leading cause of irreversible blindness, is considered as a progressive optic neuropathy often caused by elevated intraocular pressure (IOP) consequent to abnormally high resistance to aqueous humor (AH) drainage via the trabecular meshwork (TM) and Schlemm's canal. Morphological and biochemical analyses of the TM of patients with POAG revealed the loss of cells, increased accumulation of extracellular matrix proteins (ECM), changes in the cytoskeleton, cellular senescence, and the process of subclinical inflammation. The TM is the target tissue of glaucoma in the anterior chamber, and the development and progression of glaucoma are accompanied by the accumulation of oxidative damage in this tissue. The separate studies were conducted to comparatively evaluate the sensitivity to oxidative stress and lipid peroxidation (LPO) of anterior chamber tissues including TM. Accumulation of the primary, secondary, and end products of LPO (diene and triene conjugates, Schiff's bases) was noted in the studied extracts. Significant differences in the levels of all mentioned LPO products in comparison with the control were observed. The data may be considered as an evidence of LPO participation in the destruction of the trabecule and Schlemm's canal in POAG. Treatment of TM cells with oxidative stress induced POAG-typical changes such as ECM accumulation, cell death, disarrangement of the cytoskeleton, advanced senescence, and the release of inflammatory markers. By pretreatment with antioxidants, prostaglandin

  14. [Open-angle glaucoma clinical presentation and management].

    PubMed

    Kitazawa, Y

    2001-12-01

    Both primary open-angle and normal-tension glaucoma belong to an identical spectrum of diseases. Clinical presentations of primary open-angle or high-tension glaucoma (POAG) and normal-tension glaucoma (NTG) were studied in an attempt to determine prognostic, clinical factors and define the appropriate management. Clinical data obtained from 826 primary open-angle and normal-tension glaucoma patients were analyzed. In addition, the results of laboratory studies, including the immunological assay of heat shock protein (hsp) and gene analyses which were undertaken to identify risk factors at the molecular level, are discussed. 1. The identified prognostic factors were disk hemorrhage, peripapillary chorioretinal atrophy (PPA), maximum intraocular pressure (IOP), the recovery rate of skin temperature after exposure to cold, family history of glaucoma, systemic systolic channel blood pressure, and oral administration of Ca(2+)-channel antagonists. 2. Disk hemorrhage was observed in 30.5% of NTG patients and 15.4% of POAG patients. Cumulative probability of hemorrhagic events was 16.9% in POAG and 38.4% in NTG patients at the end of a 14.8-year follow-up. 3. The hazard ratio of disk hemorrhage decreased with the increase of IOP(26%/5 mmHg) and was 1.46 times higher in females than in males. Disk hemorrhage was closely associated with PPA: PPA becomes greater in association with the progression of glaucomatous optic neuropathy in both POAG and NTG. No such correlation was noted in primary angle-closure glaucoma. 4. Color Doppler imaging analyses and the hourly determination of ocular perfusion pressure (OPP) indicated a difference in retrobulbar hemodynamics between OPP-mean deviation concordant and OPP-mean deviation discordant patients: a circulatory disturbance causally unrelated to OPP seems to be involved in the OPP-mean deviation discordant patients. 5. The oral administration of Ca(2+)-channel antagonists was shown to favorably influence retrobulbar hemodynamics

  15. 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.

  16. 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.

  17. Generation of reactive oxygen species in the anterior eye segment. Synergistic codrugs of N-acetylcarnosine lubricant eye drops and mitochondria-targeted antioxidant act as a powerful therapeutic platform for the treatment of cataracts and primary open-angle glaucoma.

    PubMed

    Babizhayev, Mark A

    2016-12-01

    Senile cataract is a clouding of the lens in the aging eye leading to a decrease in vision. Symptoms may include faded colors, blurry vision, halos around light, trouble with bright lights, and trouble seeing at night. This may result in trouble driving, reading, or recognizing faces. Cataracts are the cause of half of blindness and 33% of visual impairment worldwide. Cataracts result from the deposition of aggregated proteins in the eye lens and lens fiber cells plasma membrane damage which causes clouding of the lens, light scattering, and obstruction of vision. ROS induced damage in the lens cell may consist of oxidation of proteins, DNA damage and/or lipid peroxidation, all of which have been implicated in cataractogenesis. The inner eye pressure (also called intraocular pressure or IOP) rises because the correct amount of fluid can't drain out of the eye. With primary open-angle glaucoma, the entrances to the drainage canals are clear and should be working correctly. The clogging problem occurs further inside the drainage canals, similar to a clogged pipe below the drain in a sink. The excessive oxidative damage is a major factor of the ocular diseases because the mitochondrial respiratory chain in mitochondria of the vital cells is a significant source of the damaging reactive oxygen species superoxide and hydrogen peroxide. However, despite the clinical importance of mitochondrial oxidative damage, antioxidants have been of limited therapeutic success. This may be because the antioxidants are not selectively taken up by mitochondria, but instead are dispersed throughout the body, ocular tissues and fluids' moieties. This work is an attempt to integrate how mitochondrial reactive oxygen species (ROS) are altered in the aging eye, along with those protective and repair therapeutic systems believed to regulate ROS levels in ocular tissues and how damage to these systems contributes to age-onset eye disease and cataract formation. Mitochondria

  18. 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

  19. 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

  20. Evolution of the Jet Opening Angle Distribution in Holographic Plasma

    NASA Astrophysics Data System (ADS)

    Rajagopal, Krishna; Sadofyev, Andrey V.; van der Schee, Wilke

    2016-05-01

    We use holography to analyze the evolution of an ensemble of jets, with an initial probability distribution for their energy and opening angle as in proton-proton (p p ) collisions, as they propagate through an expanding cooling droplet of strongly coupled plasma as in heavy ion collisions. We identify two competing effects: (i) each individual jet widens as it propagates and (ii) because wide-angle jets lose more energy, energy loss combined with the steeply falling perturbative spectrum serves to filter wide jets out of the ensemble at any given energy. Even though every jet widens, jets with a given energy can have a smaller mean opening angle after passage through the plasma than jets with that energy would have had in vacuum, as experimental data may indicate.

  1. Evolution of the Jet Opening Angle Distribution in Holographic Plasma.

    PubMed

    Rajagopal, Krishna; Sadofyev, Andrey V; van der Schee, Wilke

    2016-05-27

    We use holography to analyze the evolution of an ensemble of jets, with an initial probability distribution for their energy and opening angle as in proton-proton (pp) collisions, as they propagate through an expanding cooling droplet of strongly coupled plasma as in heavy ion collisions. We identify two competing effects: (i) each individual jet widens as it propagates and (ii) because wide-angle jets lose more energy, energy loss combined with the steeply falling perturbative spectrum serves to filter wide jets out of the ensemble at any given energy. Even though every jet widens, jets with a given energy can have a smaller mean opening angle after passage through the plasma than jets with that energy would have had in vacuum, as experimental data may indicate. PMID:27284647

  2. 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

  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. Recent advances in primary Sjogren's syndrome

    PubMed Central

    Holdgate, Nicholas; St.Clair, E. Wiliam

    2016-01-01

    Primary Sjögren’s syndrome, a chronic inflammatory process, is among the most commonly occurring rheumatologic diseases. The clinical hallmark of this disease is exocrine gland dysfunction, resulting predominately in dry eyes and dry mouth. However, the disease often extends beyond the exocrine glands to seriously affect other organs systems, such as the lungs, kidneys, and nervous system. Moreover, patients with primary Sjögren’s syndrome develop non-Hodgkin’s B cell lymphoma at a substantially higher rate than the general population. New research has improved our understanding of disease mechanisms, with notable advances in our knowledge about the genetic susceptibility of disease, the molecular details of the chronic inflammatory response in the salivary glands, and the complex role of the type 1 interferon pathway. The pipeline of drugs under development for the treatment of primary Sjögren’s syndrome is enriched with novel biologics and small molecular entities targeting the pathogenic process. Herein, we summarize the latest advances in elucidating the pathogenesis of primary Sjögren’s syndrome and highlight new drugs in clinical development aiming to reverse the glandular dysfunction and favorably impact the systemic features of this disease. PMID:27347394

  5. Advances in Primary Central Nervous System Lymphoma.

    PubMed

    Patrick, Lauren B; Mohile, Nimish A

    2015-12-01

    Primary central nervous system lymphoma (PCNSL) is a rare form of non-Hodgkin lymphoma that is limited to the CNS. Although novel imaging techniques aid in discriminating lymphoma from other brain tumors, definitive diagnosis requires brain biopsy, vitreoretinal biopsy, or cerebrospinal fluid analysis. Survival rates in clinical studies have improved over the past 20 years due to the addition of high-dose methotrexate-based chemotherapy regimens to whole-brain radiotherapy. Long-term survival, however, is complicated by clinically devastating delayed neurotoxicity. Newer regimens are attempting to reduce or eliminate radiotherapy from first-line treatment with chemotherapy dose intensification. Significant advances have also been made in the fields of pathobiology and treatment, with more targeted treatments on the horizon. The rarity of the disease makes conducting of prospective clinical trials challenging, requiring collaborative efforts between institutions. This review highlights recent advances in the biology, detection, and treatment of PCNSL in immunocompetent patients. PMID:26475775

  6. 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

  7. [Primary treatment of advanced Hodgkin's disease].

    PubMed

    Illés, Arpád; Udvardy, Miklós; Molnár, Zsuzsa

    2005-01-30

    Primary treatment of advanced Hodgkin's disease. Hodgkin's disease is one of the few malignant diseases that can be cured even in an advanced stage in the majority of cases. By employing a polychemotherapy containing anthracyclines, a long remission and recovery can be achieved in 60-70% of the patients. At present the standard treatment is ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) scheme for the following reasons: besides good treatment results early side effects are more favourable; sterility and secondary acute leukemia present themselves less often than by employing regimens containing alkylating agents. Unfortunately, some of the patients do not react properly to the treatment and about one third of the patients who are in remission following primary treatment will relapse at a later stage. The main goal is now to further improve treatment (recovery) results without an increase, or even a decrease of early or late side effects. Awareness of prognostic factors should lead to the employment of a less intensive but not toxic therapy in patients with good prognosis to prevent overtreatment, while in cases with bad prognosis a more effective regimen is needed (even for the price of expected complications). The latest meta-analysis on the subject has shown that--similarly to sequential high dose therapy--the addition of radiotherapy to an effective chemotherapy does not seem to prolong the survival of patients. Despite the excellent therapeutic results achieved by the many new "intensive" chemotherapies, there is unfortunately no optimal therapy or protocol available today. The multicentre analysis to confirm these results and to compare them with standard scheme is still under way. It is to be hoped that risk adapted management for advanced stage Hodgkin's disease will also be available soon. PMID:15773586

  8. Clinical Characteristics of Juvenile-onset Open Angle Glaucoma

    PubMed Central

    Kwun, Youngkyo; Lee, Eun Jung; Han, Jong Chul

    2016-01-01

    Purpose To demonstrate the clinical characteristics of juvenile-onset open angle glaucoma (JOAG) and to evaluate the prognostic factors for visual field (VF) progression in eyes with JOAG. Methods The medical records of 125 eyes of 72 patients with JOAG were analyzed retrospectively. At least four reliable VF tests were required to determine the VF progression, and the progression was defined using the modified Anderson criteria. Comparisons in clinical manifestations among groups were performed using independent t-test, and generalized estimating equations were also conducted. Results The mean follow-up duration was 94.4 ± 50.5 months. Patients with JOAG showed a male preponderance (64 %), myopia (−4.99 ± 4.01 diopters) and a severe elevation of intraocular pressure (35.6 ± 10.8 mmHg). Forty-two JOAG patients (58 %) had complained of symptoms associated with vision and pain; however, one-third presented with no definite symptoms. Fifty-seven patients were diagnosed with JOAG in both eyes, and they were significantly older (p = 0.039) and had a greater family history (p = 0.035) than patients with unilateral JOAG. The progression group exhibited a significantly higher intraocular pressure at the last visit (p = 0.023) than the non-progression group. Conclusions Because patients with considerable JOAG had no definite symptoms, periodic eye examinations are needed. To prevent the VF's progression, JOAG patients may require more careful management of intraocular pressure. PMID:27051261

  9. Eye Conditions in Older Adults: Open-Angle Glaucoma.

    PubMed

    Iroku-Malize, Tochi; Kirsch, Scott

    2016-06-01

    Glaucoma is the leading cause of irreversible vision loss in the United States, affecting 1.9% of individuals older than 40 years. The prevalence of the most common form, open-angle glaucoma, increases with age and is higher in non-Hispanic minorities. The progressive loss of peripheral vision in glaucoma often leads to difficulty with driving, particularly at night, and can increase the risk of falls and subsequent fractures. Although glaucoma usually is characterized by chronically elevated intraocular pressure, it is more accurately defined as an optic neuropathy. Typically, there are no warning signs or symptoms, and extensive and permanent optic nerve damage can occur before the patient is aware of visual field loss. A cup to disc ratio greater than 0.6 on ophthalmoscopy is suspicious for glaucoma, and visual field testing results show a characteristic peripheral loss. Medical and surgical treatments are aimed at decreasing intraocular pressure by decreasing production of aqueous humor and increasing its outflow. Drugs for glaucoma treatment include prostaglandin analogs, beta blockers, alpha2-adrenergic agonists, and carbonic anhydrase inhibitors. Surgical or laser treatment is indicated if medical management is unsuccessful. Alternative therapies are less effective and have more adverse effects than standard treatments. PMID:27348527

  10. Management of advanced primary urethral carcinomas.

    PubMed

    Dayyani, Farshid; Hoffman, Karen; Eifel, Patricia; Guo, Charles; Vikram, Raghu; Pagliaro, Lance C; Pettaway, Curtis

    2014-07-01

    Primary urethral carcinoma (PUC) is a rare malignancy accounting for <1% of genitourinary cancers, with a predilection for men and African-Americans. The sites and histology of urethral carcinoma vary by gender and anatomical location. Squamous cell carcinoma is most common among both genders but adenocarcinomas are noted in 15-35% of cases among women. Obstructive or irritative symptoms and haematuria are common modes of presentation. Clinical evaluation includes cystourethroscopy with biopsy and examination under anaesthesia. Magnetic resonance imaging provides a highly effective method to image the primary tumour while defıning the potential involvement of surrounding structures. Most tumours are localised, with regional metastases to nodal sites seen in up to 30% of cases in both genders, while distant metastases at presentation are rare (0-6%), but occur in up to 40% of cases with recurrent disease. Among men, the two most important prognostic factors are disease location and stage. Low-stage tumours (T1-2) and tumours involving the fossa navicularis or the penile urethra have a better prognosis than higher stage tumours (>T2 or N+) and lesions involving the bulbomembranous urethra. In women, in addition to stage and location, the size of the tumour has also prognostic implications. While surgery and radiation therapy (RT) are of benefit in early stage disease, advanced stage PUC requires multimodal treatment strategies to optimise local control and survival. These include induction chemotherapy followed by surgery or RT and concurrent chemoradiation with or without surgery. The latter strategy has been used successfully to treat other human papillomavirus-related cancers of the vagina, cervix and anus and may be of value in achieving organ preservation. Given the rarity of PUC, prospective multi-institutional studies are needed to better define the optimal treatment approach for this disease entity. PMID:24447439

  11. Association Between Peripheral Vascular Endothelial Function and Progression of Open-Angle Glaucoma.

    PubMed

    Liu, Chun-Hsiu; Su, Wei-Wen; Shie, Shian-Sen; Cheng, Shih-Tsung; Su, Cheng-Wen; Ho, Wang-Jing

    2016-03-01

    The aim of the study is to evaluate the relationship between Humphrey visual field progression and peripheral vascular endothelial function in patients with open-angle glaucoma (OAG), assessed by noninvasive endothelium-dependent flow-mediated vasodilation (FMD).Forty OAG patients, among which 22 had normal-tension glaucoma (NTG) and 18 had primary open-angle glaucoma (POAG) were enrolled. Each enrolled patient underwent a thorough ophthalmological examination including the Humphrey visual field test and measurement of FMD via high-resolution 2-dimensional ultrasonographic imaging of the brachial artery. Blood samples were evaluated for biochemistry and lipid profiles as well as levels of high-sensitivity C-reactive protein (hsCRP). The annual change of threshold sensitivity of the visual field in each test location were analyzed with pointwise linear regression. The correlation between long-term visual field progression and FMD was evaluated.A mean follow-up of 7.47 ± 1.84 years revealed a faster progression rate over the superior visual field in all 40 OAG patients (superior field -0.24 ± 0.67 dB/y, inferior field -0.10 ± 0.59 dB/y, P = 0.37). However, only the annual sensitivity change of the inferior peripheral field showed correlation with baseline FMD. There was no significant difference in the change slope of visual field between NTG and POAG patients.A correlation between baseline brachial artery FMD and visual field progression was observed in the inferior peripheral field in patients with NTG and POAG. This result suggests that peripheral vascular endothelial dysfunction may be related to glaucoma progression. PMID:26962832

  12. Experimental investigation on argon cluster sizes for conical nozzles with different opening angles

    NASA Astrophysics Data System (ADS)

    Chen, Guanglong; Kim, Byunghoon; Ahn, Byungnam; Kim, Dong Eon

    2010-09-01

    Using Rayleigh scattering measurement, we experimentally studied the effect of the opening angle of conical nozzles on the average sizes of argon clusters produced by high-pressure argon gas (up to 50 bars) expanding into vacuum. Both the scattering signal intensity and the scattering image were synchronically recorded by a photomultiplier tube and a charge-coupled device camera. These measurements allow for the comparison of average cluster sizes among conical nozzles of different opening angles. The experimental results indicate that, as expected by Hagena's scaling law, the argon cluster size is dependent on the opening angle. However, it is also found that (1) the cluster size exhibits a larger deviation from Hagena's scaling law at high backing pressure for a nozzle of a smaller opening angle and (2) the smaller the opening angle of conical nozzle gets, the weaker the pressure dependence of cluster size becomes.

  13. Activity of lysosomal enzymes of blood in open-angle glaucoma

    NASA Astrophysics Data System (ADS)

    Sokolov, Vladimir A.; Stroev, Evgeney A.; Cherkunov, Boris P.; Mironenko, Larisa V.

    1997-05-01

    Recently more attention has been given to the role of the lysosomal enzymes in the development of various pathological conditions. There were indications on the participation of lysosomal ferments in the development of various eye diseases such as glaucoma. Studies on the (beta) - galactosidase and cathepsins B and D activity in the blood's serum of patients with primary open-angle glaucoma were conducted. The activity of enzymes was determined by the spectrophotometry method. Cardiovascular and chronic lungs diseases accompanied ones in the main group. Patients included in the control group were of the same age and with the similar somatic patholegym. Statistically authentic galactosidase activity in the serum of patients with glaucoma as compared with control group was statistically unauthentic. Cathepsin B activity in the serum of patients with glaucoma was authentically increased at all stages of disease. In the contrary, cathepsin D activity increased at stages 2 and 3 in comparison with the control. On the basis of these studies we come to conclusion that primary glaucoma is accompanied by the increase of activity of cathepsins B and D in the serum.

  14. 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.

  15. 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

  16. 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

  17. [Functional morphology of the outflow pathways of aqueous humor and their changes in open angle glaucoma].

    PubMed

    Tamm, E R

    2013-11-01

    Aqueous humor exits the eye through the trabecular and uveoscleral outflow pathways. Under normal conditions intraocular pressure is maintained in the trabecular outflow pathways in which aqueous humor passes through the trabecular meshwork into Schlemm's canal. Intraocular pressure is generated through an outflow resistance in the juxtacanalicular region which consists of juxtacanalicular tissue and the inner wall endothelium of Schlemm's canal. The resistance of this region is under the influence of two contractile systems, the anterior longitudinal portion of the ciliary muscle and the contractile myofibroblast-like cells in the trabecular outflow pathways. Resistance is lowered through contraction of the ciliary muscle or relaxation of the contractile cells in the trabecular outflow pathways. In primary open angle glaucoma, resistance in the juxtacanalicular region is abnormally high. The cause of the increase is related to an increased activity in transforming growth factor beta and connective tissue growth factor signaling. The cells of the trabecular meshwork outflow pathways are stimulated to form a stronger contractile phenotype involving both an increase in the actin cytoskeleton and the surrounding fibrillar extracellular matrix. As a result there is an increase in cellular tone in the trabecular outflow pathways leading to an increase in rigidity and outflow resistance. PMID:24231909

  18. 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. PMID:26527516

  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. Association between systemic oxidative stress and visual field damage in open-angle glaucoma

    PubMed Central

    Tanito, Masaki; Kaidzu, Sachiko; Takai, Yasuyuki; Ohira, Akihiro

    2016-01-01

    Local and systemic oxidative stress in intraocular pressure (IOP) elevation and optic nerve damage may be involved in the pathogenesis of glaucoma. We reported previously that a lower level of systemic antioxidative capacity is associated with IOP elevation in open-angle glaucoma (OAG). We assessed the correlation between the visual field sensitivity value, i.e., mean deviation (MD), and systemic levels of prooxidants and antioxidants by analyzing the blood biochemistry in 202 patients with glaucoma. Serum levels of lipid peroxides, ferric-reducing activity, and thiol antioxidant activity were measured using the diacron reactive oxygen metabolite (dROM), biological antioxidant potential (BAP), and sulfhydryl (SH) tests, respectively, using a free-radical analyzer. Univariate and multivariate analyses suggested a positive correlation between MD and BAP (R = 0.005 and P = 0.0442 by a multiple regression model adjusted for seven demographic parameters), but no significant associations between the MD and the dROM (R = 0.002 and P = 0.8556) and SH tests (R = −0.001 and P = 0.8280). Use of more antiglaucoma medication and primary OAG rather than normal tension glaucoma also were associated significantly with worse visual field damage. This large and comprehensive assessment of the association between systemic redox status and visual field damage in OAG suggests that lower systemic antioxidant capacity measured by ferric-reducing activity is associated with more severe visual field damage in OAG that partly explained its roles in IOP elevation. PMID:27165400

  1. Estimating Long GRB Jet Opening Angles and Rest-Frame Energetics

    NASA Astrophysics Data System (ADS)

    Goldstein, Adam; Connaughton, Valerie; Briggs, Michael; Burns, Eric

    2016-03-01

    We present a method to estimate the jet opening angles of long Gamma-Ray Bursts (GRBs) using the prompt gamma-ray energetics and 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 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 expand the number of GRBs that can be used in this analysis by more than an order of magnitude. 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. A.G. is funded by the NASA Postdoctoral Program through USRA.

  2. Estimating Long GRB Jet Opening Angles and Rest-Frame Energetics

    NASA Astrophysics Data System (ADS)

    Goldstein, Adam; Connaughton, Valerie; Briggs, Michael Stephen; Burns, Eric

    2016-04-01

    We present a method to estimate the jet opening angles of long duration Gamma-Ray Bursts (GRBs) using the prompt gamma-ray energetics and 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 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 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.

  3. Estimating Long GRB Jet Opening Angles and Rest-frame Energetics

    NASA Astrophysics Data System (ADS)

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

    2016-02-01

    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.

  4. Role of primary surgery in advanced ovarian cancer

    PubMed Central

    Münstedt, Karsten; Franke, Folker E

    2004-01-01

    Background Major issues in surgery for advanced ovarian cancer remain unresolved. Existing treatment guidelines are supported by a few published reports and fewer prospective randomized clinical trials. Methods We reviewed published reports on primary surgical treatment, surgical expertise, inadequate primary surgery/quality assurance, neoadjuvant chemotherapy, interval debulking, and surgical prognostic factors in advanced ovarian cancer to help resolve outstanding issues. Results The aim of primary surgery is a well-planned and complete intervention with optimal staging and surgery. Surgical debulking is worthwhile as there are further effective treatments available to control unresectable residual disease. Patients of gynecologic oncology specialist surgeons have better survival rates. This may reflect a working 'culture' rather than better technical skills. One major problem though, is that despite pleas to restrict surgery to experienced surgeons, specialist centers are often left to cope with the results of inadequate primary surgical resections. Patients with primary chemotherapy or those who have had suboptimal debulking may benefit from interval debulking. A proposal for a better classification of residual tumor is given. Conclusions Optimal surgical interventions have definite role to play in advanced ovarian cancers. Improvements in surgical treatment in the general population will probably improve patients' survival when coupled with improvements in current chemotherapeutic approaches. PMID:15461788

  5. Primary advanced esophago-gastric melanoma: A rare case

    PubMed Central

    Wang, Lin; Zong, Liang; Nakazato, Hidetsugu; Wang, Wen-Yue; Li, Chao-Feng; Shi, Yan-Fen; Zhang, Guo-Chao; Tang, Tao

    2016-01-01

    Primary esophageal or gastric melanoma is a very rare disease with early metastasis. Due to its atypical symptom and less efficiency of chemotherapy and radiotherapy, the prognosis of esophageal or gastric melanoma is still very poor. Surgical resection remains the preferential treatment for esophageal or gastric melanoma. Here we present an extremely rare case of primary advanced esophago-gastric melanoma. Debulking surgery was performed without chemotherapy or radiotherapy. However, abdominal recurrence and hepatic metastases were found within one month by a postoperative follow-up computed tomography. Three and a half months after surgical resection, the patient died of extensive abdominal metastasis. PMID:27004009

  6. Different strategies and cost-effectiveness in the treatment of primary open angle glaucoma

    PubMed Central

    Ting, Naomi SJ; Li Yim, James FT; Ng, Jia Y

    2014-01-01

    Glaucoma is the second highest cause of blindness worldwide with an estimated half of the glaucoma population unaware of their disease. To date, intraocular pressure is the most important modifiable risk factor and lowering it has been proven to reduce progression of visual field loss associated with glaucoma. Different strategies are available to lower intraocular pressure and include medical, laser, or surgical treatment in the form of topical or systemic medications, argon or selective laser trabeculoplasty, and glaucoma drainage surgery such as trabeculectomy, deep sclerectomy, or other drainage devices. The effectiveness of these treatments has been well documented however their cost-effectiveness between the developed world and third world remains unclear. PMID:25506233

  7. 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

  8. Peripapillary Choroidal Thickness and Open-Angle Glaucoma: A Meta-Analysis

    PubMed Central

    Lin, Zhongjing; Huang, Shouyue; Xie, Bing; Zhong, Yisheng

    2016-01-01

    Purpose. To investigate the potential relationship between open-angle glaucoma (OAG) and peripapillary choroidal thickness (PPCT). Materials and Methods. Relevant publications were searched systematically through various databases from inception to January 2016. Studies comparing PPCT in OAG patients and healthy controls were retrieved. All qualified articles were analyzed using Stata 14.0 and Revman 5.3 software. Results. A total of 13 studies were identified for inclusion. There was a significant reduction of average PPCT in OAG patients compared to control participants (WMD = −24.07, 95% CI: −34.29, −13.85). Reduction of PPCT was significant in the superior (WMD = −28.87, 95% CI: −44.96, −12.78) and nasal (WMD = −21.75, 95% CI: −41.52, −1.98) sectors, but there was no significant reduction of PPCT in the inferior (WMD = −9.57, 95% CI: −36.55, 17.40) and temporal (WMD = −13.85, 95% CI: −35.40, 7.70) sectors. No obvious publication bias was detected. Conclusions. This meta-analysis suggests that open-angle glaucoma patients have significantly decreased peripapillary choroidal thickness compared to healthy individuals. Peripapillary choroidal thickness measured by optical coherence tomography may be an important parameter to consider in open-angle glaucoma. PMID:27298732

  9. Peripapillary Choroidal Thickness and Open-Angle Glaucoma: A Meta-Analysis.

    PubMed

    Lin, Zhongjing; Huang, Shouyue; Xie, Bing; Zhong, Yisheng

    2016-01-01

    Purpose. To investigate the potential relationship between open-angle glaucoma (OAG) and peripapillary choroidal thickness (PPCT). Materials and Methods. Relevant publications were searched systematically through various databases from inception to January 2016. Studies comparing PPCT in OAG patients and healthy controls were retrieved. All qualified articles were analyzed using Stata 14.0 and Revman 5.3 software. Results. A total of 13 studies were identified for inclusion. There was a significant reduction of average PPCT in OAG patients compared to control participants (WMD = -24.07, 95% CI: -34.29, -13.85). Reduction of PPCT was significant in the superior (WMD = -28.87, 95% CI: -44.96, -12.78) and nasal (WMD = -21.75, 95% CI: -41.52, -1.98) sectors, but there was no significant reduction of PPCT in the inferior (WMD = -9.57, 95% CI: -36.55, 17.40) and temporal (WMD = -13.85, 95% CI: -35.40, 7.70) sectors. No obvious publication bias was detected. Conclusions. This meta-analysis suggests that open-angle glaucoma patients have significantly decreased peripapillary choroidal thickness compared to healthy individuals. Peripapillary choroidal thickness measured by optical coherence tomography may be an important parameter to consider in open-angle glaucoma. PMID:27298732

  10. Advanced access: reducing waiting and delays in primary care.

    PubMed

    Murray, Mark; Berwick, Donald M

    2003-02-26

    Delay of care is a persistent and undesirable feature of current health care systems. Although delay seems to be inevitable and linked to resource limitations, it often is neither. Rather, it is usually the result of unplanned, irrational scheduling and resource allocation. Application of queuing theory and principles of industrial engineering, adapted appropriately to clinical settings, can reduce delay substantially, even in small practices, without requiring additional resources. One model, sometimes referred to as advanced access, has increasingly been shown to reduce waiting times in primary care. The core principle of advanced access is that patients calling to schedule a physician visit are offered an appointment the same day. Advanced access is not sustainable if patient demand for appointments is permanently greater than physician capacity to offer appointments. Six elements of advanced access are important in its application balancing supply and demand, reducing backlog, reducing the variety of appointment types, developing contingency plans for unusual circumstances, working to adjust demand profiles, and increasing the availability of bottleneck resources. Although these principles are powerful, they are counter to deeply held beliefs and established practices in health care organizations. Adopting these principles requires strong leadership investment and support. PMID:12597760

  11. 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.

  12. 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

  13. Mutated myocilin and heterozygous Sod2 deficiency act synergistically in a mouse model of open-angle glaucoma.

    PubMed

    Joe, Myung Kuk; Nakaya, Naoki; Abu-Asab, Mones; Tomarev, Stanislav I

    2015-06-15

    Glaucoma is a multifactorial optic neuropathy characterized by retinal ganglion cell (RGC) death and axonal degeneration leading to irreversible blindness. Mutations in the myocilin (MYOC) gene are the most common genetic factors of primary open-angle glaucoma. To develop a genetic mouse model induced by the synergistic interaction of mutated myocilin and another significant risk factor, oxidative stress, we produced double-mutant mice (Tg-MYOC(Y437H/+)/Sod2(+/-)) bearing human MYOC with a Y437H point mutation and a heterozygous deletion of the gene for the primary antioxidant enzyme, superoxide dismutase 2 (SOD2). Sod2 is broadly expressed in most tissues including the trabecular meshwork (TM) and heterozygous Sod2 knockout mice exhibit the reduced SOD2 activity and oxidative stress in all studied tissues. Accumulation of Y437H myocilin in the TM induced endoplasmic reticulum stress and led to a 45% loss of smooth muscle alpha-actin positive cells in the eye drainage structure of 10- to 12-month-old Tg-MYOC(Y437H/+)/Sod2(+/-) mice as compared with wild-type littermates. Tg-MYOC(Y437H/+)/Sod2(+/-) mice had higher intraocular pressure, lost about 37% of RGCs in the peripheral retina, and exhibited axonal degeneration in the retina and optic nerve as compared with their wild-type littermates. Single-mutant littermates containing MYOC(Y437H/+) or Sod2(+/-) exhibited no significant pathological changes until 12 months of age. Additionally, we observed elevated expression of endothelial leukocyte adhesion molecule-1, a human glaucoma marker, in the TM of Tg-MYOC(Y437H/+)/Sod2(+/-) mice. This is the first reported animal glaucoma model that combines expression of a glaucoma-causing mutant gene and an additional mutation mimicking a deleterious environment factor that acts synergistically. PMID:25740847

  14. Mutated myocilin and heterozygous Sod2 deficiency act synergistically in a mouse model of open-angle glaucoma

    PubMed Central

    Joe, Myung Kuk; Nakaya, Naoki; Abu-Asab, Mones; Tomarev, Stanislav I.

    2015-01-01

    Glaucoma is a multifactorial optic neuropathy characterized by retinal ganglion cell (RGC) death and axonal degeneration leading to irreversible blindness. Mutations in the MYOCILIN (MYOC) gene are the most common genetic factors of primary open-angle glaucoma. To develop a genetic mouse model induced by the synergistic interaction of mutated myocilin and another significant risk factor, oxidative stress, we produced double-mutant mice (Tg-MYOCY437H/+/Sod2+/−) bearing human MYOC with a Y437H point mutation and a heterozygous deletion of the gene for the primary antioxidant enzyme, superoxide dismutase 2 (SOD2). Sod2 is broadly expressed in most tissues including the trabecular meshwork (TM) and heterozygous Sod2 knockout mice exhibit the reduced SOD2 activity and oxidative stress in all studied tissues. Accumulation of Y437H myocilin in the TM induced endoplasmic reticulum stress and led to a 45% loss of smooth muscle alpha-actin positive cells in the eye drainage structure of 10- to 12-month-old Tg-MYOCY437H/+/Sod2+/− mice as compared with wild-type littermates. Tg-MYOCY437H/+/Sod2+/− mice had higher intraocular pressure, lost about 37% of RGCs in the peripheral retina, and exhibited axonal degeneration in the retina and optic nerve as compared with their wild-type littermates. Single-mutant littermates containing MYOCY437H/+ or Sod2+/− exhibited no significant pathological changes until 12 months of age. Additionally, we observed elevated expression of endothelial leukocyte adhesion molecule-1, a human glaucoma marker, in the TM of Tg-MYOCY437H/+/Sod2+/− mice. This is the first reported animal glaucoma model that combines expression of a glaucoma-causing mutant gene and an additional mutation mimicking a deleterious environment factor that acts synergistically. PMID:25740847

  15. 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.

  16. 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.

  17. 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.

  18. Diabetes Mellitus as a Risk Factor for Open-Angle Glaucoma: A Systematic Review and Meta-Analysis

    PubMed Central

    Zhou, Minwen; Wang, Wei; Huang, Wenbin; Zhang, Xiulan

    2014-01-01

    Objective To determine the association between diabetes mellitus (DM) and primary open-angle glaucoma (POAG). Methods This is a systematic review and meta-analysis of case-control and cohort studies. The literature search included two databases (PubMed and Embase) and the reference lists of the retrieved studies. Separate meta-analyses for case-control studies and cohort studies were conducted using random-effects models, with results reported as adjusted odds ratios (ORs) and relative risks (RRs), respectively. Results Thirteen studies—seven case-control studies and six population-based cohort studies—were included in this meta-analysis. The pooled RR of the association between DM and POAG based on the risk estimates of the six cohort studies was 1.40 (95% CI, 1.25–1.57). The pooled OR of the association between DM and POAG based on the risk estimates of the seven case-control studies was 1.49 (95% CI, 1.17–1.88). There was considerable heterogeneity among the case-control studies that reported an association between DM mellitus and POAG (P<0.001) and no significant heterogeneity among the cohort studies (P = 0.377). After omitting the case-control study that contributed significantly to the heterogeneity, the pooled OR for the association between DM and POAG was 1.35 (95% CI, 1.06–1.74). Conclusions Individuals with DM have an increased risk of developing POAG. PMID:25137059

  19. Levels of circulating homocysteine, vitamin B6, vitamin B12, and folate in different types of open-angle glaucoma

    PubMed Central

    Turgut, Burak; Kaya, Murat; Arslan, Sermal; Demir, Tamer; Güler, Mete; Kaya, Mehmet Kaan

    2010-01-01

    Objective: To compare the levels of plasma homocysteine (Hcy), vitamin B6 (vit-B6), serum vitamin B12 (vit-B12), and folate in healthy individuals and in patients with normal tension glaucoma (NTG), pseudoexfoliative glaucoma (PXG), or primary open-angle glaucoma (POAG). Study design: A prospective controlled trial. Participants and methods: Forty healthy subjects, 48 patients with NTG, 38 patients with PXG, and 34 patients with POAG were included in the study. Those who used vitamin supplements or medications affecting Hcy and vitamin levels were excluded from the study. The levels of Hcy and vit-B6 were measured by High Performance Liquid Chromatography (HPLC). The levels of serum vit-B12 and folic acid were measured by competitive chemiluminescent enzyme immunoassay (CEI). One-way analysis if variance (ANOVA), analysis of covariance (ANCOVA), and the Tukey honestly significant difference test were used for statistical analysis. Results: The mean Hcy level of the PXG group was 15.46 ± 9.27 μmol/L which was significantly higher (P = 0.03) than that of the control group. There were no statistical differences in serum vit-B12 and folate levels among control subjects and NTG, PXG and POAG groups (P > 0.05). It was found that the mean plasma vit-B6 level was significantly higher in subjects with NTG (P = 0.03) and POAG (P = 0.025) versus controls. Mean vit-B6 levels in NTG and POAG were 30.50 ± 11.29 μg/L and 30 ± 12.15 μg/L, respectively. Conclusions: The plasma level of Hcy was found to be increased only in PXG patients and the plasma levels of vit-B6 were found to increase in the NTG and POAG sample groups. Using homocysteine and vit-B6 levels as the determinants of hyperhomocysteinemia still needs further research. PMID:20458351

  20. Relationship between consecutive deterioration of mean deviation value and progression of visual field defect in open-angle glaucoma

    PubMed Central

    Naito, Tomoko; Yoshikawa, Keiji; Mizoue, Shiro; Nanno, Mami; Kimura, Tairo; Suzumura, Hirotaka; Takeda, Ryuji; Shiraga, Fumio

    2015-01-01

    Purpose To analyze the relationship between consecutive deterioration of mean deviation (MD) value and glaucomatous visual field (VF) progression in open-angle glaucoma (OAG), including primary OAG and normal tension glaucoma. Patients and methods The subjects of the study were patients undergoing treatment for OAG who had performed VF tests at least 10 times with a Humphrey field analyzer (SITA standard, C30-2 program). The VF progression was defined by a significantly negative MD slope (MD slope worsening) at the final VF test during the follow-up period. The relationship between the MD slope worsening and the consecutive deterioration of MD value were retrospectively analyzed. Results A total of 165 eyes of 165 patients were included in the analysis. Significant progression of VF defects was observed in 72 eyes of 72 patients (43.6%), while no significant progression was evident in 93 eyes of 93 patients (56.4%). There was significant relationship between the frequency of consecutive deterioration of MD value and MD slope worsening (P<0.0001, Cochran–Armitage trend test). A significant association was observed for MD slope worsening in the eyes with three (odds ratio: 2.1, P=0.0224) and four (odds ratio: 3.6, P=0.0008) consecutive deterioration of MD value in multiple logistic regression analysis, but no significant association in the eyes with two consecutive deterioration (odds ratio: 1.1, P=0.8282). The eyes with VF progression had significantly lower intraocular pressure reduction rate (P<0.01). Conclusion This retrospective study has shown that three or more consecutive deterioration of MD value might be a predictor to future significant MD slope worsening in OAG. PMID:26648689

  1. Does Helicobacter pylori Eradication Reduce the Risk of Open Angle Glaucoma in Patients With Peptic Ulcer Disease?

    PubMed

    Chen, Hsin-Yi; Lin, Cheng-Li; Chen, Wen-Chi; Kao, Chia-Hung

    2015-09-01

    To investigate whether Helicobacter pylori (H pylori) eradication would influence the risk of primary open angle glaucoma (POAG) in patients with peptic ulcer disease. From the Longitudinal Health Insurance Database 2000, 6061 patients with peptic ulcer and receiving H pylori eradication therapy were recruited. The study cohort was subdivided into early (within 1 year) and late (after 1 year) eradication cohorts. The 24,244 control cohort subjects were those who without peptic ulcer and without receiving H pylori eradication therapy and were frequency-matched with the H pylori eradication cohort by age, sex, and the year of receiving H pylori eradication therapy. The higher incidence of POAG was observed in late H pylori eradication cohort and in early H pylori eradication cohort than in control cohort (1.57, 1.32, and 0.95, per 1000 person-year, respectively). However, overall risk of glaucoma was not significantly higher in the late eradication than in the early eradication (adjusted hazard ratio = 0.85, 95% confidence interval = 0.48-1.53). The POAG incidence was greater in the late H pylori eradication cohort when follow-up duration ≤ 5 years (1.59, per 1000 person-years). However, when follow-up duration >5 years, the incidence of POAG was greater in the early H pylori eradication cohort (1.68, per 1000 person-years). These relationships were not associated with a significantly increased or decreased risk of POAG in multivariable analyses. Either early or late H pylori eradication does not significantly reduce the risk of glaucoma in patients with peptic ulcer disease compared with normal control. PMID:26426633

  2. Does Helicobacter pylori Eradication Reduce the Risk of Open Angle Glaucoma in Patients With Peptic Ulcer Disease?

    PubMed Central

    Chen, Hsin-Yi; Lin, Cheng-Li; Chen, Wen-Chi; Kao, Chia-Hung

    2015-01-01

    Abstract To investigate whether Helicobacter pylori (H pylori) eradication would influence the risk of primary open angle glaucoma (POAG) in patients with peptic ulcer disease. From the Longitudinal Health Insurance Database 2000, 6061 patients with peptic ulcer and receiving H pylori eradication therapy were recruited. The study cohort was subdivided into early (within 1 year) and late (after 1 year) eradication cohorts. The 24,244 control cohort subjects were those who without peptic ulcer and without receiving H pylori eradication therapy and were frequency-matched with the H pylori eradication cohort by age, sex, and the year of receiving H pylori eradication therapy. The higher incidence of POAG was observed in late H pylori eradication cohort and in early H pylori eradication cohort than in control cohort (1.57, 1.32, and 0.95, per 1000 person-year, respectively). However, overall risk of glaucoma was not significantly higher in the late eradication than in the early eradication (adjusted hazard ratio = 0.85, 95% confidence interval = 0.48–1.53). The POAG incidence was greater in the late H pylori eradication cohort when follow-up duration ≤5 years (1.59, per 1000 person-years). However, when follow-up duration >5 years, the incidence of POAG was greater in the early H pylori eradication cohort (1.68, per 1000 person-years). These relationships were not associated with a significantly increased or decreased risk of POAG in multivariable analyses. Either early or late H pylori eradication does not significantly reduce the risk of glaucoma in patients with peptic ulcer disease compared with normal control. PMID:26426633

  3. 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

  4. Levobetaxolol hydrochloride: a review of its pharmacology and use in the treatment of chronic open-angle glaucoma and ocular hypertension.

    PubMed

    Quaranta, Luciano; Turano, Raffaele; Pizzolante, Teodoro

    2007-06-01

    Levobetaxolol is a cardioselective beta-blocker that has been demonstrated to reduce intraocular pressure in patients affected with primary open-angle glaucoma and ocular hypertension. Levobetaxolol may be an effective neuroprotectant because of its great capacity to block sodium and calcium influx, which might confer a neuroprotective activity. Experimental and clinical studies have demonstrated the effects of levobetaxolol on ocular hemodynamics and visual field, and the pharmacologic differences between beta-blockers currently used for the treatment of elevated IOP have become of more than academic interest since a number of studies have shown improvements to various extents. Unlike the initially manufactured 0.5% ophthalmic solution, levobetaxolol is suspended in a different delivery vehicle in levobetaxolol ophthalmic suspension, to increase the ocular tolerance and allow a similarity of effect with a 2-fold reduced concentration (0.25%). PMID:19668496

  5. Levobetaxolol hydrochloride: a review of its pharmacology and use in the treatment of chronic open-angle glaucoma and ocular hypertension

    PubMed Central

    Quaranta, Luciano; Turano, Raffaele; Pizzolante, Teodoro

    2007-01-01

    Levobetaxolol is a cardioselective β-blocker that has been demonstrated to reduce intraocular pressure in patients affected with primary open-angle glaucoma and ocular hypertension. Levobetaxolol may be an effective neuroprotectant because of its great capacity to block sodium and calcium influx, which might confer a neuroprotective activity. Experimental and clinical studies have demonstrated the effects of levobetaxolol on ocular hemodynamics and visual field, and the pharmacologic differences between β-blockers currently used for the treatment of elevated IOP have become of more than academic interest since a number of studies have shown improvements to various extents. Unlike the initially manufactured 0.5% ophthalmic solution, levobetaxolol is suspended in a different delivery vehicle in levobetaxolol ophthalmic suspension, to increase the ocular tolerance and allow a similarity of effect with a 2-fold reduced concentration (0.25%). PMID:19668496

  6. 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.

  7. 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. PMID:25230966

  8. 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.

  9. Risk of open angle glaucoma due to tumor necrosis factor alpha gene polymorphisms

    PubMed Central

    Hamid, Mona Abdel; Moemen, Leqaa; Labib, Hany; Helmy, Hazem; Elsergany, Tarek

    2016-01-01

    Introduction Axonal degeneration and retinal ganglion cell apoptosis in glaucoma is associated with tumor necrosis factor alpha (TNF-α), which is an important pro-inflammatory cytokine. The aim of this study was to determine the association between the risk of open angle glaucoma (OAG) in the Egyptian population and tumor necrosis factor alpha (TNF-α) gene polymorphisms. Methods Sixty OAG patients and 26 healthy unrelated controls were used to analyze TNF-α polymorphism G-308A using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Results the GG genotype was found at a higher frequency in the controls than in the patients, and the AA and GA genotypes were associated strongly with OAG. Conclusion In this study, we found that the TNF-α polymorphism G-308A was associated significantly with OAG in the Egyptian population. However, there is a need for population-based studies with large numbers of subjects. Also, long-term follow up is required to verify the association between TNF-α polymorphism G-308A and glaucoma susceptibility. PMID:27054008

  10. Physics and evolution of constant opening angle jets using a quasi-one-dimensional magnetohydrodynamic model

    NASA Technical Reports Server (NTRS)

    Koupelis, Theodoros

    1994-01-01

    We discuss the significance of the assumptions of infinite conductivity and time independence in the context of an ideal MHD model for constant opening angle jets. The model is developed by projecting the MHD equations onto the jet axis. We find that for initially sub-Alfvenic flows (i.e., flows emanating from active galactic nuclei and neutron stars) wind-type solutions exist only when the field lines at the origin are wound up in a direction opposite to the direction of rotation of the compact source. We discuss the possibility that the time evolution of these outflows may be a cycle between breeze- and wind-type solutions as a result of continuous changes in the boundary conditions at the origin due to accretion. We propose that such cycles may explain the apparent one-sideness of some jets, especially the ones for which we cannot use arguments of relativistic beaming. We examine the dependence of the wind-type solutions on the following parameters describing the outflow at the origin: the degree of winding of the field lines, the value of the gas pressure, the polytropic index, the strength of the magnetic field, the value of the rotational velocity, the gravitational potential of the compact object, and the injection velocity. We compare results with results obtained previously, and discuss briefly the qualitative features and physical interpretation of the solutions for outflows emanating from neutron stars and protostars.

  11. 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

  12. 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

  13. Prospective, noncomparative, nonrandomized case study of short-term outcomes of 360° suture trabeculotomy ab interno in patients with open-angle glaucoma

    PubMed Central

    Sato, Tomoki; Hirata, Akira; Mizoguchi, Takanori

    2015-01-01

    Background In this paper, we describe 360° suture trabeculotomy (360°LOT) ab interno and the short-term course in patients who underwent this procedure. Methods We prospectively studied 12 patients (12 eyes) with open-angle glaucoma who underwent 360°LOT ab interno at the Sato Eye Clinic between February and July 2014. The surgical procedure involved making a 1.7 mm temporal corneal incision, exposing an approximately 15° opening in the inner wall of Schlemm’s canal (nasal side) using a Trabectome with a gonioscope, and inserting a 5-0 nylon suture rounded at the tip into Schlemm’s canal opened via the anterior chamber. The suture was then threaded around Schlemm’s canal, and the tip of the suture that emerged on the other side was then advanced through the opening to make a circumferential incision. Intraocular pressure (IOP), number of anti-glaucoma medications used, complications, and the surgery completion rate were prospectively studied. Results Mean IOP, which was 19.4 mmHg at baseline, showed a significant decrease at each of the monthly observation points, reaching 13.8 mmHg at 6 months after surgery (P=0.0004, paired t-test). The mean number of anti-glaucoma medications decreased from 3.2 at baseline to 1.1 at 6 months after surgery. IOP spikes ≥30 mmHg were seen in 25% of patients, but there were no other serious complications and the surgery completion rate was 92%. Conclusion The 360°LOT ab interno procedure preserves the conjunctiva and sclera, and has a high surgery completion rate when using the anterior chamber approach, and could therefore be an effective short-term treatment of open-angle glaucoma. PMID:25609906

  14. A new empirical calibration of the quartz c-axis fabric opening-angle deformation thermometer

    NASA Astrophysics Data System (ADS)

    Faleiros, F. M.; Moraes, R.; Pavan, M.; Campanha, G. A. C.

    2016-03-01

    The opening-angle of quartz c-axis fabrics (OA) is strongly temperature dependent and has proven to be a powerful deformation thermometer for natural metamorphic rocks. Previous considerations of empirical data have identified a linear correlation between OA and temperature between 250 and 650 °C, and no correlation above 650 °C. However, possible effects of pressure have not been investigated. We expanded the data set of OA versus temperature, including data from rocks deformed over 300-1050 °C and 2.5-15 kbar. Disregarding possible effects of pressure, the OA-temperature relationship can be described by two linear correlations for the intervals ~ 250-650 °C and ~ 650-1050 °C: The change on the curve slope of the OA-temperature relationship correlates approximately to the low- to high-quartz transition and to changes in the dynamic recrystallization mechanism from subgrain rotation to grain boundary migration. The available data suggest that pressure has a secondary effect accompanying the major temperature dependence of OA, which is particularly important for temperatures above 650 °C, where the correlation between OA and temperature is less pronounced. For fixed pressures, the OA has logarithmic relationships with temperature over the range 250-1050 °C. The following thermometer equation is formulated from a multiple regression: An uncertainty of ± 50 °C is inherited from the petrological temperature estimates of the natural samples. The data suggest the gradual increasing importance of prism [c] slip relative to < a > slip in quartz with rising temperature. Under conditions of 'average' geological strain rate and water weakening, prism [c] slip dominates for deformation above ~ 700 °C.

  15. 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.

  16. Association Between Statin Use and Open-angle Glaucoma in Hyperlipidemia Patients

    PubMed Central

    Chen, Hsin-Yi; Hsu, Sheng-Yao; Chang, Yue-Cune; Lin, Che-Chen; Sung, Fung-Chang; Chen, Wen-Chi; Kao, Chia-Huang

    2015-01-01

    Abstract The aim of the study was to investigate the association between statin use and open-angle glaucoma (OAG) risk in hyperlipidemia patients. We used the research database of the Taiwan National Health Insurance program to conduct a population-based case-control study. A total of 1276 patients with newly diagnosed OAG were identified from 2004 to 2011. Controls comprised of 12,760 patients without glaucoma and were frequency-matched for age, sex, history of diabetes mellitus, and year of hyperlipidemia diagnosis at a 1:10 ratio. Accumulated defined daily doses (DDDs) of statins prescribed during follow-up were calculated. Average statin use was calculated as the sum of DDDs divided by the duration from the initial statin prescription date to the index date (per year), and was subdivided into 3 levels: <30, 30 to 119, and ≥120 DDDs. Comorbidity, including hypertension, depression, and the Charlson comorbidity index, the frequency of eye care visits, and the use of nonstatin cholesterol-lowering drugs, were all considered as confounding factors. For the group with statin use, the adjusted odds ratio of OAG was 1.02 (95% confidence interval 0.90–1.15) when compared with the group without statin use. Subanalysis showed that a high dosage of statin use (≥120 DDD/y) resulted in a1.24-fold increased risk of OAG (odds ratio 1.24, 95% confidence interval 1.03–1.49). The incidence of OAG was increased with the increase of the dosage of statin use (P for trend = 0.0458). Clinicians should be cautious of hyperlipidemia patients with a high dosage of statin use because it might be associated with an increased risk of OAG. Ophthalmologist consultation is necessary for this high-risk group. PMID:26559301

  17. 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

  18. 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.

  19. 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

  20. Recent advances in diagnosis and treatment of primary aldosteronism.

    PubMed

    Veglio, F; Morello, F; Rabbia, F; Leotta, G; Mulatero, P

    2003-08-01

    Primary aldosteronism is the most common form of secondary hypertension. The use of aldosterone/plasma renin activity ratio (ARR) as a screening test has elevated its prevalence up to 10% of hypertensive patients. Idiopathic bilateral adrenal hyperplasia and aldosterone-producing adrenal adenoma are the leading causes of primary aldosteronism. Most patients with this conditions are normokalemic and clinically undistinguishable from essential hypertensives. However, they suffer from anticipated and more severe target organ damage than other hypertensives. Thus, being primary aldosteronism a common, specifically treatable and sometimes surgically cured form of hypertension, a prompt diagnosis is necessary and cannot be overlooked. The measurement of ambulatory ARR represents the screening test and should be performed in the majority of hypertensive patients. ARR higher than a set cutoff suggests the need of a confirmatory test for primary aldosteronism, such as intravenous saline load or fludrocortisone suppression test. If inability to suppress aldosterone is demonstrated, the disease is confirmed. The subtype evaluation is based on adrenal imaging (CT scan) and selective adrenal venous sampling. The latter is the gold standard for the diagnosis of a lateralized aldosterone secretion, as typically observed in aldosterone-producing adenomas. Microadenomas are frequently overlooked by adrenal image. If lateralization is confirmed, unilateral adrenalectomy is the reasonable therapeutic option, leading to a significant reduction of blood pressure, if not normotension. If bilateral aldosterone excess is demonstrated, an aldosterone receptor antagonist should be administered. This article reviews and discusses the new data about prevalence, diagnosis and treatment of primary aldosteronism. PMID:14605590

  1. 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.

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

    PubMed

    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

  3. 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

  4. Advances in neonatal screening for primary immune deficiencies

    PubMed Central

    JIANG, TINGTING; LI, ZHENGUANG; ZHANG, QIULI

    2016-01-01

    The congenital disorders of immune competence are known as primary immunodeficiencies (PID) and are mainly characterized by a pathological susceptibility to infection. These infections are mostly of time repetitive and drug resistant in nature. The number of infected infants has reached over 200 and is on the increase. Additionally, clinical severity of the disease has been confirmed to be extensive. The increasing number of these severe PIDs is due to the lack of specific as well as efficient management avenues. New assays and concepts for newborn screening of severe primary immune deficiencies are being explored and the present review focused on these new upcoming strategies for improved screening of neonates. PMID:27168770

  5. 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.…

  6. 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.

  7. 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.

  8. Trabecular-Iris Circumference Volume in Open Angle Eyes Using Swept-Source Fourier Domain Anterior Segment Optical Coherence Tomography

    PubMed Central

    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. PMID:25210623

  9. 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. PMID:25210623

  10. 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.

  11. Advanced Imaging for Biopsy Guidance in Primary Brain Tumors

    PubMed Central

    Tsiouris, Apostolos J; Ramakrishna, Rohan

    2016-01-01

    Accurate glioma sampling is required for diagnosis and establishing eligibility for relevant clinical trials. MR-based perfusion and spectroscopy sequences supplement conventional MR in noninvasively predicting the areas of highest tumor grade for biopsy. We report the case of a patient with gliomatosis cerebri and multifocal patchy enhancement in whom the combination of advanced and conventional imaging attributes successfully guided a diagnostic biopsy. PMID:27014538

  12. 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

  13. [Advance in molecular genetic research on primary congenital glaucoma].

    PubMed

    Li, Xiulan; Liu, Haotian; Zhang, Dingding

    2016-04-01

    Primary congenital glaucoma (PCG) is one of the major diseases causing blindness in children, but its pathogenesis has remained unclear. Genetic factors play an important role in the pathogenesis of PCG. Molecular genetics of candidate genes such as CYP1B1, MYOC, LTBP2 and FOXC1 has so far been explored, but no disease-causing gene has been identified. Molecular genetic research on PCG including candidate gene screening and research strategies are reviewed here. PMID:27060330

  14. Resin transfer molding for advanced composite primary wing and fuselage structures

    NASA Technical Reports Server (NTRS)

    Markus, Alan

    1992-01-01

    The stitching and resin transfer molding (RTM) processes developed at Douglas Aircraft Co. are successfully demonstrating significant cost reductions with good damage tolerance properties. These attributes were identified as critical to application of advanced composite materials to commercial aircraft primary structures. The RTM/stitching developments, cost analyses, and test results are discussed of the NASA Advanced Composites Technology program.

  15. Advances in the genetics of primary torsion dystonia

    PubMed Central

    Valente, Enza Maria

    2010-01-01

    Knowledge about the genetics of primary torsion dystonia (PTD) has been progressing at a very slow pace compared with other movement disorders. For many years, only one causative gene was known, DYT1/TOR1A, yet the recent identification of a second PTD causative gene (DYT6/THAP1), the detection of subclinical alterations caused by mutations in PTD genes in some healthy non-penetrant individuals, and functional studies on TOR1A and THAP1 protein products have significantly improved mutation detection, genotype-phenotype correlates, and our understanding of the cellular mechanisms underlying the development of dystonia. PMID:20948792

  16. 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.

  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. PMID:25732405

  18. Severe Primary HSV-2 in a Perinatal HIV-Infected Woman with Advanced Immunosuppression

    PubMed Central

    Lee, Lana; Agwu, Allison; Hutton, Nancy

    2012-01-01

    Herpes simplex virus type 2 (HSV-2) is most commonly associated with mucocutaneous manifestations; however, coinfections with HIV may be associated with atypical and more severe presentations of clinical disease. We present a case of a young woman with advanced perinatally acquired AIDS presenting with severe purulent pharyngitis, fevers, and toxic appearance with a subsequent diagnosis of disseminated primary HSV-2 infection in multiple noncontiguous mucocutaneous sites. This case highlights an unusual presentation of the protean nature of primary HSV infection and the potential severity of illness in patients with advanced immunosuppression. PMID:22899940

  19. 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

  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. Systematic review and meta-analysis on the efficacy of selective laser trabeculoplasty in open-angle glaucoma.

    PubMed

    Wong, Mandy Oi Man; Lee, Jacky Wai Yip; Choy, Bonnie Nga Kwan; Chan, Jonathan Cheuk Hung; Lai, Jimmy Shiu Ming

    2015-01-01

    Selective laser trabeculoplasty (SLT) is a relatively new type of laser used in treating open-angle glaucoma (OAG) and is reported to be equally efficacious to a first-line medication and argon laser trabeculoplasty (ALT). We summarize available evidence for considering SLT as an alternative treatment in OAG through systematic review and meta-analysis. Among OAG patients who range from newly diagnosed to those on maximally tolerated medical therapy, SLT results in a 6.9-35.9% intraocular pressure (IOP) reduction. Complications are rare and include an IOP spike requiring surgery, persistent macular edema, and corneal haze and thinning. Meta-analysis of randomized, controlled trials shows that SLT is non-inferior to ALT and medication in IOP reduction and also in achieving treatment success. Number of medications reduction is similar between SLT and ALT. More robust evidence is needed to determine its efficacy as a repeated procedure. PMID:25113610

  2. [Surgical results of dissection of the superficial temporal artery in patients with preglaucoma and initial open-angle glaucoma].

    PubMed

    Shilkin, G A; Iartseva, N S; Mironova, E M; Oreshkina, R M; Mikhaĭlova, G D

    1989-01-01

    Results of superficial temporal artery dissection performed in 42 patients (44 eyes) with preglaucoma and initial open-angle glaucoma have shown no impairement of visual field, visual acuity, optic disc in the period from 0.5 to 1.5 years after it. The increased linear rate of bloodflow after the operation remained stable in 17 eyes of patients with preglaucoma and in 14 eyes of patients with glaucoma. Intraocular pressure became normalized in 20 and 19 eyes as well as intraocular fluid outflow in 14 and 13 eyes, respectively. In both groups there was a tendency to normalization of retinal functions and hydrodynamics of the eye. Thus, the operation produces improvement of regional bloodflow, tonographic and electrophysiologic indices. Its usage is considered to be reasonable, but, when determining indications to it, an individual approach is necessary. PMID:2755669

  3. Efficacy and safety of 1% forskolin eye drops in open angle glaucoma – An open label study

    PubMed Central

    Majeed, Muhammed; Nagabhushanam, Kalyanam; Natarajan, Sankaran; Vaidyanathan, Priti; Karri, Suresh Kumar; Jose, Jyolsna Agnes

    2015-01-01

    Purpose Current treatment for glaucoma includes beta-blockers and prostaglandin analogues which have their own disadvantages. Thus a need exists for new ocular hypotensive agents that are more efficacious and have fewer side effects. Therefore, forskolin eye drops 1%, through herbal product; a clinical trial was carried out for the safety and efficacy in the treatment of open angle glaucoma. Methods Ninety adult male/female patients of 18–60 years of age, of either sex, suffering from open angle glaucoma with an intraocular pressure (IOP) of more than 24 mm Hg were enrolled in the study. Patients were advised to instill 2 drops thrice a day (8:00 h, 14:00 h and 20:00 h) and tonometric readings were recorded on baseline visit and on Visit 2, i.e. end of 1st week, Visit 3–2nd week, Visit 4–3rd week, and Visit 5–4th week. The reduction in IOP across each time point from untreated baseline visit and reduction in IOP across various study visits were measured. Results The mean (95% CI) difference in reduction in IOP was 4.5 mm Hg (P < 0.05) in the right eye and was 5.4 mm Hg (p < 0.05) in the left eye from baseline visit (Visit 1) to final visit (Visit 5). Conclusions Forskolin 1% eye drops can be a safe alternative to beta blockers in glaucoma patients having concomitant asthma. PMID:26155078

  4. 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.

  5. Brinzolamide 1%/timolol versus dorzolamide 2%/timolol in the treatment of open-angle glaucoma or ocular hypertension: prospective randomized patient-preference study

    PubMed Central

    Altafini, Romeo; Scherzer, Maria-Luise; Hubatsch, Douglas A; Frezzotti, Paolo

    2015-01-01

    Purpose The objective of this study was to assess preference for fixed-combination brinzolamide 1%/timolol 0.5% (BTFC) versus fixed-combination dorzolamide 2%/timolol 0.5% (DTFC) in patients with open-angle glaucoma or ocular hypertension. Methods In this prospective, single-masked crossover study, patients were randomized 1:1 to BTFC-DTFC or DTFC-BTFC treatment sequences. Patients self-administered each medication for 7 days, with a 48-hour washout period between treatments, and rated ocular discomfort after each treatment period. Medication preferences based on ocular comfort (primary endpoint) and anticipated adherence were assessed. Safety outcomes included adverse events and intraocular pressure. Between-group differences in treatment preference and ocular discomfort scores were analyzed using chi-square and Wilcoxon–Mann–Whitney tests, respectively. Adherence, intraocular pressure, and adverse events were summarized descriptively. Results In total, 112 patients were enrolled (mean ± SD age, 66±11 years), and 109 patients completed the study. Numerically, more patients in the intent-to-treat dataset preferred BTFC versus DTFC (59.3% versus 40.7%); however, this result was not statistically significant (treatment difference, 18.6%; P=0.0670). Mean ocular discomfort scores (range, 0–9) were statistically significantly lower with BTFC versus DTFC (2.6 versus 3.7; P=0.0002, Wilcoxon– Mann–Whitney test). More patients who preferred BTFC over DTFC were confident that they would adhere to their preferred medication. Treatment-related adverse events included blurred vision with BTFC and eye irritation or eye pain with DTFC. Conclusion BTFC and DTFC were preferred by approximately 60% and 40% of patients, respectively, and BTFC was associated with less patient-reported ocular discomfort. Greater ocular comfort of glaucoma medications may improve treatment adherence. PMID:26664041

  6. Primary Surgery or Neoadjuvant Chemotherapy in Advanced Ovarian Cancer: The Debate Continues….

    PubMed

    Leary, Alexandra; Cowan, Renee; Chi, Dennis; Kehoe, Sean; Nankivell, Matthew

    2016-01-01

    Primary debulking surgery (PDS) followed by platinum-based chemotherapy has been the cornerstone of treatment for advanced ovarian cancer for decades. Primary debulking surgery has been repeatedly identified as one of the key factors in improving survival in patients with advanced ovarian cancer, especially when minimal or no residual disease is left behind. Achieving these results sometimes requires extensive abdominal and pelvic surgical procedures and consultation with other surgical teams. Some clinicians who propose a primary chemotherapy approach reported an increased likelihood of leaving no macroscopic disease after surgery and improved patient-reported outcomes and quality-of-life (QOL) measures. Given the ongoing debate regarding the relative benefit of PDS versus neoadjuvant chemotherapy (NACT), tumor biology may aid in patient selection for each approach. Neoadjuvant chemotherapy offers the opportunity for in vivo chemosensitivity testing. Studies are needed to determine the best way to evaluate the impact of NACT in each individual patient with advanced ovarian cancer. Indeed, the biggest utility of NACT may be in research, where this approach provides the opportunity for the investigation of predictive markers, mechanisms of resistance, and a forum to test novel therapies. PMID:27249696

  7. 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

  8. Advance statement of consent from patients with primary CNS tumours to organ donation and elective ventilation.

    PubMed

    Patel, Umang Jash

    2013-03-01

    A deficit in the number of organs available for transplantation persists even with an increase in donation rates. One possible choice of donor for organs that appears under-referred and/or unaccepted is patients with primary brain tumours. In spite of advances in the treatment of high-grade primary central nervous system (CNS) tumours, the prognosis remains dire. A working group on organs from donors with primary CNS tumours showed that the risk of transmission is small and outweighs the benefits of waiting for a normal donor, in survival and organ life-years, with caveats. This paper explores the possibility that, if information on organ donation were made available to patients and their families with knowledge of their inevitable fate, perhaps some will choose to donate. It would be explained that to achieve this, elective ventilation would be performed in their final moments. This would obviate the consent question because of an advance statement. It is accepted that these are sensitive matters and there will be logistic issues. This will need discussion with the public and other professionals, but it could increase the number of donors and can be extrapolated to encompass other primary CNS tumours. PMID:23303178

  9. Short-term effects of acupuncture on open-angle glaucoma in retrobulbar circulation: additional therapy to standard medication.

    PubMed

    Takayama, Shin; Seki, Takashi; Nakazawa, Toru; Aizawa, Naoko; Takahashi, Seri; Watanabe, Masashi; Izumi, Masayuki; Kaneko, Soichiro; Kamiya, Tetsuharu; Matsuda, Ayane; Kikuchi, Akiko; Yambe, Tomoyuki; Yoshizawa, Makoto; Nitta, Shin-Ichi; Yaegashi, Nobuo

    2011-01-01

    Background. The relation between glaucoma and retrobulbar circulation in the prognosis has been indicated. Purpose. To investigate the effects of acupuncture on retrobulbar circulation in open-angle glaucoma (OAG) patients. Methods. Eleven OAG patients (20 eyes with OAG) who were treated by topical antiglaucoma medications for at least 3 months were enrolled. Acupuncture was performed once at acupoints BL2, M-HN9, ST2, ST36, SP6, KI3, LR3, GB20, BL18, and BL23 bilaterally. Retrobulbar circulation was measured with color Doppler imaging, and intraocular pressure (IOP) was also measured at rest and one hour after rest or before and after acupuncture. Results. The Δ value of the resistive index in the short posterior ciliary artery (P < .01) and the Δ value of IOP (P < .01) were decreased significantly by acupuncture compared with no acupuncture treatment. Conclusions. Acupuncture can improve the retrobulbar circulation and IOP, which may indicate the efficacy of acupuncture for OAG. PMID:21437193

  10. Systemic Hypertension as a Risk Factor for Open-Angle Glaucoma: A Meta-Analysis of Population-Based Studies

    PubMed Central

    Bae, Hyoung Won; Lee, Naeun; Lee, Hye Sun; Hong, Samin; Seong, Gong Je; Kim, Chan Yun

    2014-01-01

    Background/Aims Systemic hypertension is thought to increase the risk for developing open-angle glaucoma (OAG) through several mechanisms. However, previous epidemiological studies have shown conflicting results regarding this potential association. We systematically evaluated this issue by conducting a meta-analysis of population-based studies. Methods A comprehensive search for articles published before 31 March 2014 was performed using PubMed, Embase, and reference lists. The pooled odds ratio (OR) was calculated using the fixed- and random-effects models, and meta-regression was performed according to age. Subgroup analyses were also conducted, and publication bias was assessed using a funnel plot and Egger’s regression test. Results This meta-analysis included 16 studies involving 60,084 individuals, with substantial homogeneity among the studies. The pooled OR for OAG was 1.22 (95% confidence interval, CI: 1.09–1.36) using the fixed-effects model and 1.22 (95% CI: 1.08–1.37) using the random-effects model in all included studies. For subgroup analyses, the pooled OR for high-tension glaucoma (HTG) was higher than that for normal-tension glaucoma (NTG) (OR = 1.92 and 0.94, respectively). No significant difference was detected between Asian and Western populations, and no publication bias was detected in either analysis. Conclusions Systemic hypertension increases the risk for developing OAG, especially in those with HTG. PMID:25254373

  11. 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.

  12. Identification of MYOC gene mutation and polymorphism in a large Malay family with juvenile-onset open angle glaucoma

    PubMed Central

    Mimiwati, Z; Nurliza, K; Marini, M; Liza-Sharmini, AT

    2014-01-01

    Purpose To screen for mutations in the coding region of the myocilin (MYOC) gene in a large Malay family with juvenile-onset open angle glaucoma (JOAG). Methods A total of 122 family members were thoroughly examined and screened for JOAG. Venipuncture was conducted. Genomic DNA was extracted from peripheral blood leukocytes. The presence of a mutation and a polymorphism was ascertained with PCR amplification followed by the direct sequencing technique. Results Thirty-two of the 122 screened family members were identified to have JOAG (11 new cases and 21 known cases). An autosomal dominant inheritance pattern with incomplete penetrance was observed. A C→A substitution at position 1440 in exon 3 that changes asparagine (AAC) to lysine (AAA) was identified in affected family members except two probands (III:5 and IV:6). Six probands were identified as having the Asn480Lys mutation but have not developed the disease yet. An intronic polymorphism IVS2 730 +35 G>A was also identified. There was a significant association between Asn480Lys (p<0.001) and IVS2 730+35G>A (p<0.001) in the affected and unaffected probands in this family. Conclusions The Asn480Lys mutation and the IVS2 730+35 G>A polymorphism increased susceptibility to JOAG in this large Malay pedigree. Identifying the MYOC mutations and polymorphisms is important for providing presymptomatic molecular diagnosis. PMID:24883016

  13. Optical coherence tomography for advanced screening in the primary care office

    PubMed Central

    Shelton, Ryan L.; Jung, Woonggyu; Sayegh, Samir I.; McCormick, Daniel T.; Kim, Jeehyun; Boppart, Stephen A.

    2013-01-01

    Optical coherence tomography (OCT) has long been used as a diagnostic tool in the field of ophthalmology. The ability to observe microstructural changes in the tissues of the eye has proved very effective in diagnosing ocular disease. However, this technology has yet to be introduced into the primary care office, where indications of disease are first encountered. We have developed a portable, handheld imaging probe for use in the primary care setting and evaluated its tissue site accessibility, ability to observe diseased tissue, and screening capabilities in in vivo human patients, particularly for pathologies related to the eye, ear and skin. Various stages of diabetic retinopathy were investigated using the handheld probe and early-stage diabetic retinopathy was flagged as abnormal from the OCT images. At such early stages of disease, it is difficult to observe abnormalities with the limited tools that are currently available to primary care physicians. These results indicate that OCT shows promise to transform from being a diagnostic technology in the medical and surgical specialities to a screening technology in the primary care office and at the front-line of healthcare. In vivo cross-sectional images of four examples of common pathologies in humans encountered by a primary care physician. All images were taken using a novel handheld OCT imaging probe. (A) Human cornea after LASIK surgery. (B) Advanced diabetic retinopathy. (C) Tympanic membrane with accompanying biofilm. (D) Skin abscess showing layer separation and fluid-filled pockets. PMID:23606343

  14. Glaucoma, Open-Angle

    MedlinePlus

    ... Prevalent Cases of Glaucoma (in thousands) by Age, Gender, and Race/Ethnicity Because of their longer life ... Prevalent Cases of Glaucoma (in thousands) by Age, Gender, and Race/Ethnicity Projections for Glaucoma (2010-2030- ...

  15. Therapeutic advances for primary biliary cholangitis: the old and the new.

    PubMed

    Wang, Li; Zhang, Feng-Chun; Zhang, Xuan

    2016-06-01

    Primary biliary cholangitis (PBC, primary biliary cirrhosis) is an autoimmune cholestatic liver disease characterized by chronic nonsuppurative destructive cholangitis and the presence of serum antimitochondrial antibodies. Ursodeoxycholic acid is the only drug approved by the US Food and Drug Administration to treat PBC. However, one-third of patients show incomplete responses to ursodeoxycholic acid and a poor prognosis. A number of old and new medications have been used in these patients, such as fibrates, glucocorticoids, immunosuppressants, obeticholic acid, mesenchymal stem cells, biological agents (anti-interleukin-12, cytotoxic T-lymphocyte antigen 4 immunoglobulin, anti-CD20), and antifibrotic drugs. This article reviews the therapeutic advances of these old and new medications in patients with PBC. PMID:26862931

  16. Advances in Radiation Therapy for Primary and Metastatic Adult Soft Tissue Sarcomas.

    PubMed

    Blumenfeld, Philip; Sen, Neilayan; Abrams, Ross; Wang, Dian

    2016-06-01

    Soft tissue sarcomas (STS) consist of a heterogeneous group of rare malignancies arising from mesenchymal origin. While surgical resection is the primary treatment for STS, the use of radiotherapy (RT) as an adjunctive modality has been shown to improve oncologic outcomes. Technologic improvements, such as image guidance and intensity-modulated radiotherapy that significantly improve both the precision and delivery of RT, have led to the reduction of long-term RT toxicities without compromising outcomes. This review addresses these technologic advancements as well as discussing the most current updates regarding the use of brachytherapy, charged particles, and novel agents with RT. PMID:27113370

  17. 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.

  18. Anterior Lamina Cribrosa Surface Depth in Open-Angle Glaucoma: Relationship with the Position of the Central Retinal Vessel Trunk

    PubMed Central

    Oh, Baek-Lok; Kim, Hyunjoong; Girard, Michaël J. A.; Mari, Jean Martial; Kim, Tae-Woo

    2016-01-01

    Purpose To determine the factors influencing the anterior lamina cribrosa (LC) surface depth (LCD) in patients with open-angle glaucoma (OAG), focusing on the association between LCD and the position of the central retinal vessel trunk (CRVT) at the anterior LC surface. Methods Optic nerve heads of 205 OAG eyes were scanned using swept-source optical coherence tomography (SS-OCT). After processing the images using adaptive compensation, the LCD was determined from 11 horizontal B-scan images that divided the optic disc vertically into 12 equal parts. Eyes were divided into two groups (central or peripheral) according to where the CRVT exits from the anterior LC surface. The influence of CRVT position on LCD was evaluated, taking into account age, gender, untreated intraocular pressure (IOP), IOP at optic-disc scanning, retinal nerve fiber layer (RNFL) thickness, visual-field mean deviation, central corneal thickness, and axial length. Results Patients in the peripheral CRVT group were younger and more myopic, and had a larger mean LCD and thinner global RNFL than those in the central CRVT group (all P≤0.023). On multivariate analysis, the peripheral CRVT location was significantly associated with a larger LCD (P = 0.002), together with the significant association of younger age (P<0.001), higher untreated IOP (P = 0.010), and thinner RNFL (P = 0.003) on the larger LCD. Conclusion In OAG, CRVT location was an independent factor influencing the LCD, together with age, untreated IOP, and global RNFL thickness. The data indicate that the CRVT may contribute to the resistance of the LC against deformation. A longitudinal prospective observation is required to clarify this relationship. PMID:27355646

  19. Differences between Non-arteritic Anterior Ischemic Optic Neuropathy and Open Angle Glaucoma with Altitudinal Visual Field Defect

    PubMed Central

    Han, Sangyoun; Jung, Jong Jin

    2015-01-01

    Purpose To investigate the differences in retinal nerve fiber layer (RNFL) change and optic nerve head parameters between non-arteritic anterior ischemic optic neuropathy (NAION) and open angle glaucoma (OAG) with altitudinal visual field defect. Methods Seventeen NAION patients and 26 OAG patients were enrolled prospectively. The standard visual field indices (mean deviation, pattern standard deviation) were obtained from the Humphrey visual field test and differences between the two groups were analyzed. Cirrus HD-OCT parameters were used, including optic disc head analysis, average RNFL thickness, and RNFL thickness of each quadrant. Results The mean deviation and pattern standard deviation were not significantly different between the groups. In the affected eye, although the disc area was similar between the two groups (2.00 ± 0.32 and 1.99 ± 0.33 mm2, p = 0.586), the rim area of the OAG group was smaller than that of the NAION group (1.26 ± 0.56 and 0.61 ± 0.15 mm2, respectively, p < 0.001). RNFL asymmetry was not different between the two groups (p = 0.265), but the inferior RNFL thickness of both the affected and unaffected eyes were less in the OAG group than in the NAION group. In the analysis of optic disc morphology, both affected and unaffected eyes showed significant differences between two groups. Conclusions To differentiate NAION from OAG in eyes with altitudinal visual field defects, optic disc head analysis of not only the affected eye, but also the unaffected eye, by using spectral domain optical coherence tomography may be helpful. PMID:26635459

  20. 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.

  1. Outcomes of pelvic exenteration for recurrent or primary locally advanced colorectal cancer

    PubMed Central

    Yang, Hwa Yeon; Park, Sung Chan; Hyun, Jong Hee; Seo, Ho Kyung

    2015-01-01

    Purpose The objective of this study was to assess the clinical outcomes of pelvic exenteration for patients with primary locally advanced colorectal cancer (LACRC) or locally recurrent colorectal cancer (LRCRC), and to identify clinically relevant prognostic factors. Methods Between January 2001 and December 2010, 40 consecutive patients with primary LACRC or LRCRC underwent pelvic exenteration at the National Cancer Center, Republic of Korea. We retrospectively reviewed their medical records. Results The median age was 59 years and the median follow-up time was 26 months (range, 1-117 months). The overall complication and in-hospital mortality rates were 70% (28/40) and 7.5% (3/40), respectively. The complication rates were similar between patients with primary LACRC (69.6%) and those with LRCRC (70.6%). The overall recurrence rate was 50% (17/34), and was lower in patients with primary LACRC than in patients with LRCRC (33.3% vs. 76.9%, P = 0.032). The 5-year overall survival was significantly different between primary LACRC and patients with LRCRC (58.7% vs. 11.8%, P = 0.022). Multivariate analysis revealed that radicality (R0 vs. R1/R2) was an independent prognostic factor for overall survival (P = 0.020). Conclusion The complication and operative mortality rates of pelvic exenteration remained high, but pelvic exenteration might provide an opportunity for long-term survival and good local control. Complete (R0) resection was the only independent prognostic factor for overall survival. PMID:26366382

  2. 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

  3. Safety and efficacy of fixed-combination travoprost/timolol in patients with open-angle glaucoma or ocular hypertension not controlled with timolol monotherapy

    PubMed Central

    Jordão, Marcelo Lopes da Silva; Hatanaka, Marcelo; Ogundele, Abayomi; de Moraes Silva, Maria Rosa Bet; Vessani, Roberto Murad

    2014-01-01

    Objective To assess the intraocular pressure (IOP)-lowering effect of travoprost 0.004%/timolol 0.5% fixed-dose combination (TRAV/TIM–FC) in patients not achieving the target IOP of ≤18 mmHg while on timolol 0.5% (TIM) monotherapy. Methods A multicenter, prospective, open-label study (NCT01336569) was conducted in patients with open-angle glaucoma or ocular hypertension. Eligible patients were receiving TIM monotherapy with a screening/baseline IOP of 19–35 mmHg in ≥1 eye. TIM was discontinued on the baseline visit day (no washout period) and TRAV/TIM–FC was initiated and administered once daily at 8 pm for 4–6 weeks. The primary efficacy variable was mean change in IOP from TIM-treated baseline to study end, measured by Goldmann applanation tonometry. Results were analyzed by analysis of variance and paired samples t-test (5% significance). Results A total of 49 patients were enrolled (mean age, 63 [range, 42–82] years; 55.1% White; 73.5% women), and 45 were included in the intent-to-treat (ITT) population. Mean duration of treatment with TRAV/TIM–FC was 31 days. Mean ± standard deviation IOP reduction from baseline (TIM) to the follow-up visit (TRAV/TIM–FC) was −5.0±3.6 mmHg. IOP decreased significantly (P<0.0001) from baseline (22.1±2.6 mmHg) to study end (17.1±3.9 mmHg) in the ITT population, with a mean IOP reduction of 22.3%. Most patients (n=33/45; 73.3%) achieved IOP ≤18 mmHg. Two patients experienced a total of four adverse events (AEs), including a patient who reported one serious AE (enterorrhagia) that was considered unrelated to treatment, and a patient who reported one event each of drug-related redness, pruritus, and foreign body sensation. Most patients (n=47/49; 95.9%) reported no AEs. Conclusions TRAV/TIM–FC lowered IOP in patients who were not at target IOP while receiving TIM monotherapy, with most patients achieving an IOP ≤18 mmHg with TRAV/TIM–FC. TRAV/TIM–FC was well tolerated in this population. PMID

  4. Primary surgery versus chemoradiotherapy for advanced oropharyngeal cancers: a longitudinal population study

    PubMed Central

    2013-01-01

    Background Treatment for advanced stage oropharyngeal squamous cell carcinoma (OPSCC) includes combined chemoradiation therapy or surgery followed by radiation therapy alone or in combination with chemotherapy. The goal of this study was to utilize available evidence to examine survival outcome differences in patients with advanced stage OPSCC treated with these different modalities. Methods Patients with advanced stage OPSCC were identified. Primary outcome measurements were disease specific and overall survival rates with differences examined via Kaplan-Meier and logistic regression analysis. Results 344 patients were enrolled. 94 patients underwent triple modality therapy inclusive of surgery followed by adjuvant combined chemotherapy and radiation therapy (S-CRT). 131 had surgery and radiation therapy (S-RT), while 56 had chemoradiation (CRT) therapy as their primary treatment. A total of 63 patients had single modality radiation therapy and were excluded from analysis due to the large number of palliative patients. Kaplan-Meier overall survival analysis showed that therapy with S-CRT had the highest disease specific survival at five years (71.1%). This is contrasted against S-RT and CRT, with five year survival rates at 53.9%, and 48.6%, respectively. Cox regression showed that the comparison of S-CRT vs. S-RT, and CRT is associated with statistically significant increased hazard ratios of 1.974, and 2.785, indicating that both S-RT and CRT are associated with a reduced likelihood of survival at 5 years when compared to S-CRT. Conclusions In this population based cohort study S-CRT is associated with a 17–22% 5 year disease specific survival benefit compared to CRT or S-RT. PMID:23663568

  5. Advance care planning for cancer patients in primary care: a feasibility study

    PubMed Central

    Boyd, Kirsty; Mason, Bruce; Kendall, Marilyn; Barclay, Stephen; Chinn, David; Thomas, Keri; Sheikh, Aziz; Murray, Scott A

    2010-01-01

    Background Advance care planning is being promoted as a central component of end-of-life policies in many developed countries, but there is concern that professionals find its implementation challenging. Aim To assess the feasibility of implementing advance care planning in UK primary care. Design of study Mixed methods evaluation of a pilot educational intervention. Setting Four general practices in south-east Scotland. Method Interviews with 20 GPs and eight community nurses before and after a practice-based workshop; this was followed by telephone interviews with nine other GPs with a special interest in palliative care from across the UK. Results End-of-life care planning for patients typically starts as an urgent response to clear evidence of a short prognosis, and aims to achieve a ‘good death’. Findings suggest that there were multiple barriers to earlier planning: prognostic uncertainty; limited collaboration with secondary care; a desire to maintain hope; and resistance to any kind of ‘tick-box’ approach. Following the workshop, participants' knowledge and skills were enhanced but there was little evidence of more proactive planning. GPs from other parts of the UK described confusion over terminology and were concerned about the difficulties of implementing inflexible, policy-driven care. Conclusion A clear divide was found between UK policy directives and delivery of end-of-life care in the community that educational interventions targeting primary care professionals are unlikely to address. Advance care planning has the potential to promote autonomy and shared decision making about end-of-life care, but this will require a significant shift in attitudes. PMID:21144189

  6. 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

  7. Hepatic intra-arterial chemotherapy in patients with advanced primary liver tumours

    PubMed Central

    Spada, Francesca; Fazio, Nicola; Bonomo, Guido; Monfardini, Lorenzo; Vigna, Paolo Della; Radice, Davide; Boselli, Sabrina; Orsi, Franco

    2012-01-01

    Background: Primary liver tumours (PLTs) are currently a major health problem worldwide. The study’s aim was to investigate the feasibility, toxicity, and activity of hepatic intra-arterial chemotherapy (HIAC) in patients with advanced PLTs. Methods: We retrospectively analysed 43 patients with advanced unresectable PLT, who were consecutively treated. HIAC with 5-fluorouracil, cisplatin, and mitomycin-C was administered through a radiologically positioned temporary percutaneous catheter every six weeks until tumour progression or unacceptable toxicity was reached. Results: Partial response was observed in 26% and stable disease in 41% of patients. The median overall survival was 12.3 months. Manageable catheter-related complications occurred in 23% of patients. The grade 3–4 toxicities included neutropenia, thrombocytopenia, and transaminitis. There were no toxic deaths. Conclusion: The results of this retrospective study show that HIAC is feasible, active, and manageable in patients with PLTs. The treatment could be studied in selected patients with advanced progressive HCC/BTC being treated with or ineligible for sorafenib/cisplatin plus gemcitabine. PMID:23226162

  8. Picking up speed: advances in the genetics of primary ciliary dyskinesia

    PubMed Central

    Horani, Amjad; Brody, Steven L; Ferkol, Thomas W

    2014-01-01

    Abnormal ciliary axonemal structure and function are linked to the growing class of genetic disorders collectively known as ciliopathies, and our understanding of the complex genetics and functional phenotypes of these conditions has rapidly expanded. While progress in genetics and biology has uncovered numerous cilia-related syndromes, primary ciliary dyskinesia (PCD) remains the sole genetic disorder of motile cilia dysfunction. The first disease-causing mutation was described just thirteen years ago, and since that time the pace of gene discovery has quickened. These mutations separate into genes that encode axonemal motor proteins, structural and regulatory elements, and cytoplasmic proteins that are involved in assembly and preassembly of ciliary elements. These findings have yielded novel insights into the processes involved in ciliary assembly, structure, and function, which will allow us to better understand the clinical manifestations of primary ciliary dyskinesia. Moreover, advances in techniques for genetic screening and sequencing are improving diagnostic approaches. In this manuscript, we will describe the structure, function, and emerging genetics of respiratory cilia, review the genotype-phenotype relationships of motor ciliopathies, and explore the implications of recent discoveries for diagnostic testing for primary ciliary dyskinesia. PMID:24192704

  9. Linked opening angle and histological and mechanical aspects of the proximal pulmonary arteries of healthy and pulmonary hypertensive rats and calves.

    PubMed

    Tian, Lian; Lammers, Steven R; Kao, Philip H; Reusser, Mark; Stenmark, Kurt R; Hunter, Kendall S; Qi, H Jerry; Shandas, Robin

    2011-11-01

    Understanding how arterial remodeling changes the mechanical behavior of pulmonary arteries (PAs) is important to the evaluation of pulmonary vascular function. Early and current efforts have focused on the arteries' histological changes, their mechanical properties under in vitro mechanical testing, and their zero-stress and no-load states. However, the linkage between the histology and mechanical behavior is still not well understood. To explore this linkage, we investigated the geometry, residual stretch, and histology of proximal PAs in both adult rat and neonatal calf hypoxic models of pulmonary hypertension (PH), compared their changes due to chronic hypoxia across species, and proposed a two-layer mechanical model of artery to relate the opening angle to the stiffness ratio of the PA outer to inner layer. We found that the proximal PA remodeling in calves was quite different from that in rats. In rats, the arterial wall thickness, inner diameter, and outer layer thickness fraction all increased dramatically in PH and the opening angle decreased significantly, whereas in calves, only the arterial wall thickness increased in PH. The proposed model predicted that the stiffness ratio of the calf proximal PAs changed very little from control to hypertensive group, while the decrease of opening angle in rat proximal PAs in response to chronic hypoxia was approximately linear to the increase of the stiffness ratio. We conclude that the arterial remodeling in rat and calf proximal PAs is different and the change of opening angle can be linked to the change of the arterial histological structure and mechanics. PMID:21856906

  10. Bupropion Use and Risk of Open-Angle Glaucoma among Enrollees in a Large U.S. Managed Care Network

    PubMed Central

    Stein, Joshua D.; Talwar, Nidhi; Kang, Jae H.; Okereke, Olivia I.; Wiggs, Janey L.; Pasquale, Louis R.

    2015-01-01

    Objective Tumor Necrosis Factor (TNF) mediates retinal ganglion cell death in glaucoma. Anti-TNF drugs are neuroprotective in an animal model of glaucoma. It is unclear whether medications with anti-TNF properties such as bupropion have an impact on the risk of developing open-angle glaucoma (OAG) in humans. The purpose of this study is to determine whether bupropion use alters the risk of developing OAG. Methods Claims data for beneficiaries age ≥35 years with no pre-existing OAG enrolled in a large nationwide U.S. managed care network continuously for ≥4 years between 2001-2011 was analyzed to identify patients who had been newly-diagnosed with OAG. The amount of bupropion use as captured from outpatient pharmacy claims over a four-year period was also quantified for each beneficiary. Multivariable Cox regression modeling assessed the impact of bupropion and other antidepressant medications on the risk of developing OAG with adjustment for sociodemographic characteristics of the enrollees along with medical and ocular comorbidities. Results Of 638,481 eligible enrollees, 15,292 (2.4%) developed OAG. After adjustment for confounding factors including use of other antidepressant medication classes, each additional month of bupropion use was associated with a 0.6% reduced risk of OAG (HR = 0.994, (95% CI: 0.989-0.998), p = 0.007). Compared to nonusers, those with 24-48 months of bupropion use had a 21% reduced hazard (HR=0.79, (CI: 0.65-0.94), p = 0.0099) of OAG. This association did not differ among persons taking bupropion for depression or for other reasons (p-interaction = 0.82). There was no significant association between use of tricyclic antidepressants (HR = 1.000, (CI: 0.997-1.004), p = 0.95) or selective serotonin reuptake inhibitors (HR = 0.999, (CI: 0.997-1.001), p = 0.39) and development of OAG. Conclusion These findings suggest bupropion use may be beneficial in reducing the risk of OAG. If prospective studies confirm the findings of this analysis

  11. Association of Geroprotective Effects of Metformin and Risk of Open-Angle Glaucoma in Persons With Diabetes Mellitus

    PubMed Central

    Lin, Hsien-Chang; Stein, Joshua D.; Nan, Bin; Childers, David; Newman-Casey, Paula Anne; Thompson, Debra A.; Richards, Julia E.

    2015-01-01

    IMPORTANCE Caloric restriction mimetic drugs have geroprotective effects that delay or reduce risks for a variety of age-associated systemic diseases, suggesting that such drugs might also have the potential to reduce risks of blinding ophthalmologic conditions for which age is a major risk factor. OBJECTIVE To determine whether the caloric restriction mimetic drug metformin hydrochloride is associated with reduced risk of open-angle glaucoma (OAG) in persons with diabetes mellitus. DESIGN, SETTING, AND PATIENTS Retrospective cohort study of patients aged 40 years or older with diabetes mellitus and no preexisting record of OAG in a large US managed care network from January 1, 2001, through December 31, 2010. EXPOSURES Quantity of metformin and other prescribed diabetes medications as captured from outpatient pharmacy records. MAIN OUTCOMES AND MEASURES Risk of developing OAG. RESULTS Of 150 016 patients with diabetes mellitus, 5893 (3.9%) developed OAG. After adjusting for confounding factors, those prescribed the highest quartile of metformin hydrochloride (> 1110 g in 2 years) had a 25% reduced OAG risk relative to those who took no metformin (hazard ratio = 0.75; 95% CI, 0.59–0.95; P = .02). Every 1-g increase in metformin hydrochloride use was associated with a 0.16% reduction in OAG risk (adjusted hazard ratio = 0.99984; 95% CI, 0.99969–0.99999; P = .04), which predicts that taking a standard dose of 2 g of metformin hydrochloride per day for 2 years would result in a 20.8% reduction in risk of OAG. After accounting for potential confounders, including metformin and diabetic medications, the risk of developing OAG was increased by 8% (hazard ratio = 1.08; 95% CI, 1.03–1.13; P = .003) for each unit of increase in glycated hemoglobin level. CONCLUSIONS AND RELEVANCE Metformin use is associated with reduction in risk of developing OAG, and risk is reduced even when accounting for glycemic control in the form of glycated hemoglobin level. Other diabetes

  12. Biomodulation of capecitabine by paclitaxel and carboplatin in advanced solid tumors and adenocarcinoma of unknown primary.

    PubMed

    Mikhail, Sameh; Lustberg, Maryam B; Ruppert, Amy S; Mortazavi, Amir; Monk, Paul; Kleiber, Barbara; Villalona-Calero, Miguel; Bekaii-Saab, Tanios

    2015-11-01

    Paclitaxel and carboplatin upregulate thymidine phosphorylase and thus may provide synergistic antitumor activity in combination with capecitabine (CTX). We, therefore, performed a phase I/II study of CTX. In the phase I study, patients with advanced solid tumors received carboplatin on day 1, paclitaxel on days 1, 8, 15 and capecitabine orally twice a day on days 8-21, every 4 weeks. Phase II patients with advanced adenocarcinoma of unknown primary (ACUP) were treated at the maximal tolerable dose. The phase I study enrolled 29 patients evaluable for dose limiting toxicity. The recommended phase II dose was capecitabine 750 mg/m(2) bid, paclitaxel 60 mg/m(2)/week and carboplatin AUC of 6. There were 9 confirmed responses, 5 partial responses and disease stabilization >3 months in 14 patients. The phase II study was prematurely terminated at 25 patients due to cessation of funding. The objective response rate was 32 % (95 % CI 0.15-0.54), the median progression-free survival 5.5 months (95 % CI 2.8-10.8 months) and the median overall survival 10.8 months (95 % CI 6.0-32.0 months). CTX demonstrated acceptable tolerability and antitumor activity. At the recommended dose level in patients with ACUP, this regimen showed encouraging preliminary activity. PMID:26416564

  13. Management of locally advanced carcinoma of the breast by primary radiation therapy

    SciTech Connect

    Harris, J.R.; Sawicka, J.; Gelman, R.; Hellman, S.

    1983-03-01

    A retrospective review of 137 patients with locally advanced breast cancer, but without distant metastases, who were treated with radical radiation therapy is presented. Ninety percent of patients had an initial complete response to their radiation therapy. The 5 year rates of local tumor control, survival free of distant failure, and overall survival were 54% 28% and 30%, respectively. Multivariate analysis revealed that the following features were associated with improved local tumor control: clinically negative axillary nodes, excisional biopsy, radiation dose greater than 6000 rad, and the use of adjuvant systemic therapy. Improved freedom from distant relapse was seen in patients with small primaries and non-inflammatory carcinoma, as well as clinically negative axillary nodes, excisional biopsy, radiation dose greater than 6000 rad, and the use of adjuvant systemic therapy. The results suggest that adequate levels of radiation therapy can provide local tumor control in a significant proportion of patients with locally advanced breast cancer and that adjuvant systemic therapy is useful in improving both local tumor control and freedom from distant relapse in these patients.

  14. The primary treatment of advanced vocal cord cancer: laryngectomy or radiotherapy

    SciTech Connect

    van den Bogaert, W.; Ostyn, F.; van der Schueren, E.

    1983-03-01

    When different treatment modalities yield equal results in cancer treatment, the least mutilating is preferred. If results are different, however, the survival rate after treatment must be weighed against the quality of life. Considerable controversy exists concerning the primary treatment modality for advanced glottic cancer, with some authors defending surgery (with or without radiotherapy) and others defending radiotherapy as sole treatment, with laryngectomy reserved for local failures. From a group of 102 patients with T3 and T4 tumors, 65 were treated with a laryngectomy. Uncorrected survival at 5 years was 48%, local control was 75%. A group of 35 patients were treated with radiotherapy. Survival was 22% at 5 years, local control 23%, with rescue surgery 37%. These unfavorable results are related to the negative selection of patients for radiotherapy (inoperable, bad cooperation). In 14 patients who were operable but refused laryngectomy the final local control was 53%, with voice preservation in 34%; survival, however, remained low (27% at 5 years). Primary surgery seems to provide better chances for ultimate survival than radiotherapy alone. At the moment, it is not yet clear if a proportion of patients can be selected for whom a more conservative attitude can be allowed, with laryngectomy reserved for poor regression or recurrences after radiotherapy.

  15. Cost-effectiveness analysis review of exemestane in the treatment of primary and advanced breast cancer

    PubMed Central

    Hashemi-Meshkini, Amir; Keshavarz, Khosro; Gharibnaseri, Zahra; Kheirandish, Mehrnaz; Kebriaeezadeh, Abbas

    2013-01-01

    Introduction Exemestane was approved in 2005 for adjuvant treatment of breast cancer. In this study, we aimed to assess whether it is cost-effective in comparison to available alternatives. Material and methods To evaluate the efficacy of exemestane, a systematic review was conducted by searching electronic databases. The outcomes of interest were “clinical benefit”, “overall response” and “disease-free survival rate”. To evaluate the cost of treatments, costs of both domestic generic and imported brand medicines were taken into account, and the incremental cost-effectiveness ratio (ICER) was calculated for each comparison. Results Regarding primary breast cancer, based upon available evidence, exemestane could not be considered as a cost-effective medicine either in generic or brand form compared with placebo (ICER: 119,100 and 215,525), with tamoxifen after 2-3 years of therapy (ICER: 35,150 and 82,400) and with sequential treatment by tamoxifen and exemestane (dominated because of lower effectiveness and higher cost). In metastatic breast cancer, exemestane was not considered a cost-effective treatment compared with both anastrozole and megestrol acetate (dominated) and was highly cost-effective compared with tamoxifen (ICERs: 2,208 and 4,326 dollars per one more patient with an overall response for generic and brand medicines) although even in this case it was not cost-effective in terms of the 1-year survival rates (dominated). Conclusions Regarding current evidence and related costs in terms of Iranian pharmaceutical market prices, exemestane could not be considered a cost-effective treatment in primary and advanced breast cancer compared with available alternatives. However, more evidence is still needed for more certain decisions. PMID:23847669

  16. Comparison of ExPress Mini-Device Implantation Alone or Combined with Phacoemulsification for the Treatment of Open-Angle Glaucoma

    PubMed Central

    Stawowski, Łukasz; Konopińska, Joanna; Deniziak, Marta; Saeed, Emil; Zalewska, Renata; Mariak, Zofia

    2015-01-01

    We propose comparative assessment of the effectiveness of two surgical methods for the treatment of open-angle glaucoma: (1) ExPress mini-device implantation combined with phacoemulsification and (2) ExPress mini-device implantation alone. In this prospective study, 81 patients (88 phakic eyes) with uncontrolled open-angle glaucoma enrolled for surgery. They were assigned two groups, those with coexisting cataracts (46 eyes; P-ExPress group) and those with glaucoma alone (42 eyes; ExPress group). The follow-up period was 12.9 ± 0.4 months in P-ExPress and 12.2 ± 0.6 months in ExPress group. In both groups the following parameters were measured: best corrected visual acuity (BCVA), intraocular pressure (IOP), number of complications and necessary postoperative interventions, and number of glaucoma medications. The IOP at the end of follow-up was similar in both groups (18.8 ± 5.9 versus 18.1 ± 4.8 mmHg; P = 0.814). There were no statistical differences in the average number of glaucoma medications between ExPress and P-ExPress groups (0.9 ± 1.65 versus 1.3 ± 1.7; P = 0.419) as well as in the number of postoperative complications (26 versus 21%; P = 0.179 in the P-ExPress and ExPress groups, resp.). Both methods are safe and effective for the surgical treatment of open-angle glaucoma. Coexistence of cataracts does not constitute a compelling contraindication for combined surgery. PMID:26576293

  17. Primary chemotherapy with adriamycin, cisplatin, vincristine and cyclophosphamide in locally advanced thymomas: a single institution experience.

    PubMed

    Berruti, A; Borasio, P; Gerbino, A; Gorzegno, G; Moschini, T; Tampellini, M; Ardissone, F; Brizzi, M P; Dolcetti, A; Dogliotti, L

    1999-11-01

    From 1990 to 1997, 16 consecutive patients with stage III and IVa invasive thymoma were treated in a single institution with primary chemotherapy consisting in adriamycin (40 mg m(-2)), cisplatin (50 mg m(-2)) administered intravenously on day 1, vincristine (0.6 mg m(-2)) on day 2 and cyclophosphamide (700 mg m(-2)) on day 4 (ADOC). The courses were repeated every 3 weeks. The aim was to evaluate the impact of this cytotoxic regimen with respect to response rate, per cent of patients radically resected, time to progression and overall survival. Two complete responses (one clinical and one pathological) and 11 partial responses were observed (overall response rate 81.2%); two patients had stable disease and one progressed. Toxicity was mild as only two patients developed grade III/IV neutropenia and one patient grade III nausea/vomiting. Nine patients were radically resected (five out of ten with stage III, and four out of six with stage IVa). Median time to progression and overall survival was 33.2 and 47.5 months respectively. Three patients were alive and disease free after more than 5 years. The ADOC scheme is highly active and manageable in the treatment of locally advanced thymoma. As a preoperative approach it should be offered to patients not amenable to surgery or to those surgically resectable but with a great deal of morbidity. PMID:10555755

  18. Primary lens extraction for glaucoma management: A review article

    PubMed Central

    Eid, Tarek M.

    2011-01-01

    Recently, primary lens extraction alone gained more acceptance as an alternative surgical approach for glaucoma management. This view was supported by the advances in phacoemulsification and intraocular lenses with greater safety and visual recovery, in addition to a substantial reduction of intraocular pressure and deepening of the anterior chamber and filtration angle. The decrease in IOP after cataract surgery in primary open-angle glaucoma (POAG) is mild, less predictable, related to baseline levels, and may return to presurgical values after an initial period of reduction. Therefore, the IOP-lowering effect of primary cataract extraction in POAG may be insufficient to achieve adequate IOP control. The IOP reduction after lens extraction is consistently greater in eyes with primary angle closure glaucoma (PACG) than in eyes with POAG. Primary lens extraction in acute PACG eliminates, or at least, reduces the risk of recurrence of acute attacks and deepens the anterior chamber and widens the angle which reduces the risk of progression of peripheral anterior synechiae and development of chronic PACG. Primary lens extraction may be more preferable to glaucoma incisional surgery in mild to moderate PACG eyes with appositional angle closure. The decision to do lens extraction as a primary treatment for glaucoma should be individualized based upon several factors other than the effect on IOP. These factors include patients’ characteristics, surgeons’ skills and preferences, status of glaucoma control, type of cataract and intraocular lens implanted, and potential harm of laser treatment for late capsular opacification and fibrosis. PMID:23960947

  19. 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

  20. Pair-wise comparison analysis of differential expression of mRNAs in early and advanced stage primary colorectal adenocarcinomas

    PubMed Central

    Lau, Tze Pheng; Roslani, April Camilla; Lian, Lay Hoong; Chai, Hwa Chia; Lee, Ping Chin; Hilmi, Ida; Goh, Khean Lee; Chua, Kek Heng

    2014-01-01

    Objectives To characterise the mRNA expression patterns of early and advanced stage colorectal adenocarcinomas of Malaysian patients. Design Comparative expression analysis. Setting and participants We performed a combination of annealing control primer (ACP)-based PCR and reverse transcription-quantitative real-time PCR for the identification of differentially expressed genes (DEGs) associated with early and advanced stage primary colorectal tumours. We recruited four paired samples from patients with colorectal cancer (CRC) of Dukes’ A and B for the preliminary differential expression study, and a total of 27 paired samples, ranging from CRC stages I to IV, for subsequent confirmatory test. The tumouric samples were obtained from the patients with CRC undergoing curative surgical resection without preoperative chemoradiotherapy. The recruited patients with CRC were newly diagnosed with CRC, and were not associated with any hereditary syndromes, previously diagnosed cancer or positive family history of CRC. The paired non-cancerous tissue specimens were excised from macroscopically normal colonic mucosa distally located from the colorectal tumours. Primary and secondary outcome measures The differential mRNA expression patterns of early and advanced stage colorectal adenocarcinomas compared with macroscopically normal colonic mucosa were characterised by ACP-based PCR and reverse transcription-quantitative real-time PCR. Results The RPL35, RPS23 and TIMP1 genes were found to be overexpressed in both early and advanced stage colorectal adenocarcinomas (p<0.05). However, the ARPC2 gene was significantly underexpressed in early colorectal adenocarcinomas, while the advanced stage primary colorectal tumours exhibited an additional overexpression of the C6orf173 gene (p<0.05). Conclusions We characterised two distinctive gene expression patterns to aid in the stratification of primary colorectal neoplasms among Malaysian patients with CRC. Further work can be done to

  1. 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.

  2. 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

  3. Establishing Age-Adjusted Reference Ranges for Iris-Related Parameters in Open Angle Eyes with Anterior Segment Optical Coherence Tomography

    PubMed Central

    Peterson, Jeffrey R.; Blieden, Lauren S.; Chuang, Alice Z.; Baker, Laura A.; Rigi, Mohammed; Feldman, Robert M.; Bell, Nicholas P.

    2016-01-01

    Purpose Define criteria for iris-related parameters in an adult open angle population as measured with swept source Fourier domain anterior segment optical coherence tomography (ASOCT). Methods Ninety-eight eyes of 98 participants with open angles were included and stratified into 5 age groups (18–35, 36–45, 46–55, 56–65, and 66–79 years). ASOCT scans with 3D mode angle analysis were taken with the CASIA SS-1000 (Tomey Corporation, Nagoya, Japan) and analyzed using the Anterior Chamber Analysis and Interpretation software. Anterior iris surface length (AISL), length of scleral spur landmark (SSL) to pupillary margin (SSL-to-PM), iris contour ratio (ICR = AISL/SSL-to-PM), pupil radius, radius of iris centroid (RICe), and iris volume were measured. Outcome variables were summarized for all eyes and age groups, and mean values among age groups were compared using one-way analysis of variance. Stepwise regression analysis was used to investigate demographic and ocular characteristic factors that affected each iris-related parameter. Results Mean (±SD) values were 2.24 mm (±0.46), 4.06 mm (±0.27), 3.65 mm (±0.48), 4.16 mm (±0.47), 1.14 (±0.04), 1.51 mm2 (±0.23), and 38.42 μL (±4.91) for pupillary radius, RICe, SSL-to-PM, AISL, ICR, iris cross-sectional area, and iris volume, respectively. Both pupillary radius (P = 0.002) and RICe (P = 0.027) decreased with age, while SSL-to-PM (P = 0.002) and AISL increased with age (P = 0.001). ICR (P = 0.54) and iris volume (P = 0.49) were not affected by age. Conclusion This study establishes reference values for iris-related parameters in an adult open angle population, which will be useful for future studies examining the role of iris changes in pathologic states. PMID:26815917

  4. Wavelet-Based and Morphological Analysis of the Global Flash Multifocal ERG for Open Angle Glaucoma Characterization

    NASA Astrophysics Data System (ADS)

    Miguel-Jiménez, J. M.; Ortega, S.; Artacho, I.; Boquete, L.; Rodríguez-Ascariz, J. M.; de La Villa, P.; Blanco, R.

    This article presents one of the alternative methods developed for the early detection of ocular glaucoma based on the characterisation of mfERG (multifocal electroretinography) readings. The digital signal processing technique is based on Wavelets, hitherto unused in this field, for detection of advanced-stage glaucoma and the study of signal morphology by means of identity patterns for detection of glaucoma in earlier stages. Future research possibilities are also mentioned, such as the study of orientation in the development of the disease.

  5. Overall survival should be the primary endpoint in clinical trials for advanced non-small-cell lung cancer

    PubMed Central

    Cheema, P.K.; Burkes, R.L.

    2013-01-01

    An article in a recent edition of Current Oncology explored the validation of progression-free survival (pfs) as an endpoint in clinical trials of antineoplastic agents for metastatic colorectal cancer, metastatic renal cell carcinoma, and ovarian cancer. The support for pfs as a surrogate endpoint for overall survival (os) was elucidated. As with the aforementioned tumour types, advanced non-small-cell lung cancer (nsclc) has seen a rise in active agents since the year 2000. Those agents range from improved cytotoxics such as pemetrexed, to targeted therapies such as tyrosine kinase inhibitors of the epidermal growth factor receptor and agents that target the EML4–ALK gene mutation. More recently, it has also become apparent that histology plays an important role in the response to and outcomes of treatment. With the therapeutic options for patients with advanced nsclc increasing, concerns are being raised that the efficacy of drugs measured by os may be diluted in clinical trials, thereby underestimating their true clinical benefit. That possibility, together with the need to have efficacious drugs available to patients earlier, has resulted in the search for a surrogate to the os endpoint in advanced nsclc. The present article follows up the recent article on pfs as a surrogate. Although advances in identifying pfs as a valid surrogate endpoint for os have been made in other tumour types, in advanced nsclc, such surrogacy has not been formally validated. Until it has, os should remain the primary endpoint of clinical trials in advanced nsclc. PMID:23559882

  6. Fixed-dose combination of tafluprost and timolol in the treatment of open-angle glaucoma and ocular hypertension: comparison with other fixed-combination products.

    PubMed

    Holló, Gábor; Vuorinen, Jouni; Tuominen, Juhani; Huttunen, Teppo; Ropo, Auli; Pfeiffer, Norbert

    2014-09-01

    A new preservative-free fixed-dose combination of 0.0015% tafluprost, a prostaglandin F2α analog, and 0.5% timolol (TAF/TIM; Santen Oy, Tampere, Finland), a beta-adrenergic antagonist has recently been developed. The intraocular pressure (IOP) reduction with TAF/TIM in open-angle glaucoma and ocular hypertension is similar to that of other prostaglandin-timolol fixed-combination products. Patients with high IOP responded well to TAF/TIM with reductions of up to 40% (>13 mmHg) and beyond. Compared to previous controlled and double-masked clinical trials with DuoTrav(®) (Alcon, Fort Worth, USA) and Ganfort(®) (Allergan, Irvine, USA), TAF/TIM caused less superficial ocular side effects and less conjunctival hyperemia. Plausible explanations for the differences in side effects between the fixed-combination products are discussed. PMID:25213118

  7. Estimation of the mass loss, opening angle and mass of Be circumstellar disks from Brmathsf γ continuum emission and interferometric measurements

    NASA Astrophysics Data System (ADS)

    Stee, Ph.

    2003-06-01

    Using the SIMECA code developed by Stee & Araùjo (\\cite{stee1}); Stee et al. (\\cite{stee2}) for Be stars we obtain a correlation between the mass loss rates {dot M} and the Brgamma continuum luminosity as a function of the opening angle of the disk. We show that this correlation is similar to those obtained by Scuderi et al. (\\cite{scuderi}) for O-B supergiants. We found that the wind density at the base of the photosphere, from a sample of 8 Be stars, lies between 10-13 and 10-12 g cm-3. We also present a relationship between the mass of the circumstellar disk and the 2.16 mu m flux. Finally we emphasize how interferometric measurements can help to estimate the wind density and we present a sample of 16 Be stars with predicted visibilities that can be observed with the VLTI.

  8. Advanced material modelling in numerical simulation of primary acetabular press-fit cup stability.

    PubMed

    Souffrant, R; Zietz, C; Fritsche, A; Kluess, D; Mittelmeier, W; Bader, R

    2012-01-01

    Primary stability of artificial acetabular cups, used for total hip arthroplasty, is required for the subsequent osteointegration and good long-term clinical results of the implant. Although closed-cell polymer foams represent an adequate bone substitute in experimental studies investigating primary stability, correct numerical modelling of this material depends on the parameter selection. Material parameters necessary for crushable foam plasticity behaviour were originated from numerical simulations matched with experimental tests of the polymethacrylimide raw material. Experimental primary stability tests of acetabular press-fit cups consisting of static shell assembly with consecutively pull-out and lever-out testing were subsequently simulated using finite element analysis. Identified and optimised parameters allowed the accurate numerical reproduction of the raw material tests. Correlation between experimental tests and the numerical simulation of primary implant stability depended on the value of interference fit. However, the validated material model provides the opportunity for subsequent parametric numerical studies. PMID:22817471

  9. Perimetric progression using the Visual Field Index and the Advanced Glaucoma Intervention Study score and its clinical correlations

    PubMed Central

    Gros-Otero, Juan; Castejón, Miguel; Paz-Moreno, Javier; Mikropoulos, Dimitrios; Teus, Miguel

    2014-01-01

    Purpose To evaluate the association between clinical parameters and the diagnosis of progression using VFI (Visual Field Index) and AGIS (Advanced Glaucoma Intervention Study) score in primary open angle glaucoma. Methods Retrospective study of 517 visual fields of 78 eyes with primary open angle glaucoma analyzed with VFI and AGIS score. Clinical data registered included: age, sphere, pachimetry, basal intraocular pressure (IOP), and IOP during the follow up. Results Only the AGIS score diagnosis of progression was associated with the clinical parameters registered. Among the analyzed data, the mean IOP during follow up (p = 0.0005) and IOP at the third month of follow up (p = 0.004) were statistically associated with progression using the AGIS criteria. Conclusion The diagnosis of perimetric progression using the AGIS score in the current study was closer to the real functional progression than the diagnosis using the VFI, as the former was associated with known risk factors for progression in glaucoma. PMID:25182851

  10. Measurement of tumor necrosis factor-alpha, interleukin-6, Fas ligand, interleukin-1α, and interleukin-1β in the aqueous humor of patients with open angle glaucoma using multiplex bead analysis

    PubMed Central

    Borkenstein, Andreas; Faschinger, Christoph; Maier, Richard; Weger, Martin; Theisl, Anna; Demel, Ulrike; Graninger, Winfried; Irene, Holzer

    2013-01-01

    Purpose Various cytokines, including tumor necrosis factor-alpha (TNF-α), Fas ligand (FasL), interleukin-1α (IL-1α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), contribute to the pathogenesis of primary open angle glaucoma (POAG). The present study was set to measure these cytokines in the aqueous humor of patients with POAG and in control subjects using multiplex bead analysis. Methods Twenty-five patients with POAG and 29 control subjects were enrolled in this case-control study. Aqueous humor concentrations of the cytokines (IL-1 α, IL-1 β, IL-6, FasL, and TNF- α) were measured using multiplex bead analysis. Results Mean aqueous humor levels of IL-6 were significantly lower in patients with POAG compared to the control subjects (9.3±23.7 versus 55.3±94.4 pg/ml; p=0.002). No significant difference in the aqueous humor concentration of IL-1β was found between patients with POAG and control subjects (0.5±0.8 versus 0.4±0.8 pg/ml; p=0.85.) Concentrations of IL-1α, TNF-α, and FasL were below limits of detection. No significant correlation was found between IL-6 concentration and age, duration of disease, cup/disc ratio, or mean deviation. Conclusions In the present study, we found significantly lower concentrations of IL-6 in the aqueous humor of patients with POAG. PMID:24265545

  11. 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…

  12. Debridement arthroplasty for advanced primary osteoarthritis of the elbow. Results of a new technique used for 29 elbows.

    PubMed

    Tsuge, K; Mizuseki, T

    1994-07-01

    We report the technique and results of a new method of debridement arthroplasty for advanced primary osteoarthritis of the elbow. Triceps and the periosteum of the olecranon are reflected towards the ulnar side and the joint is opened by dividing the radial collateral ligament. Osteophytes are removed, the olecranon and coronoid fossae are deepened and the fibrosed anterior joint capsule is excised. The degenerative changes are always more advanced on the radial side, with erosion of the capitellum, and it is usually necessary to remodel the head of the radius. In 29 elbows reviewed at a mean of 64 months, the average gain of range of motion was 34 degrees, with good pain relief and improved grip in most patients. Two elbows required reoperation but there were no other serious complications. PMID:8027156

  13. 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. PMID:25470307

  14. 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

  15. Comparative studies of RNFL thickness measured by OCT with global index of visual fields in patients with ocular hypertension and early open angle glaucoma

    PubMed Central

    Taliantzis, Sergios; Papaconstantinou, Dimitris; Koutsandrea, Chrysanthi; Moschos, Michalis; Apostolopoulos, Michalis; Georgopoulos, Gerasimos

    2009-01-01

    Purpose: To compare the functional changes in visual fields with optical coherence tomography (OCT) findings in patients with ocular hypertension, open angle glaucoma, and suspected glaucoma. In addition, our purpose is to evaluate the correlation of global indices with the structural glaucomatous defect, to assess their statistical importance in all the groups of our study, and to estimate their validity to the clinical practice. Methods: One hundred sixty nine eyes (140 patients) were enrolled. The patients were classified in three groups. Group 1 consisted of 54 eyes with ocular hypertension, group 2 of 42 eyes with preperimetric glaucoma, and group 3 of 73 eyes with chronic open angle glaucoma. All of them underwent ophthalmic examination according to a prefixed protocol, OCT exam (Stratus 3000) for retinal nerve fiber layer (RNFL) thickness measurement with fast RNFL thickness protocol and visual fields (VF) examination with Octopus perimeter (G2 program, central 30–2 threshold strategy). Pearson correlation was calculated between RNFL thickness and global index of VF. Results: A moderate correlation between RNFL thickness and indices mean sensitivity (MS), mean defect (MD) and loss variance (LV) of VF (0.547, −0.582, −0.527, respectively; P <0.001) was observed for all patients. Correlations of the ocular hypertension and preperimetric groups are weak. Correlation of RNFL thickness with global indices becomes stronger as the structural alterations become deeper in OCT exam. Correlation of RNFL thickness with the global index of VF, in respective segments around optic disk was also calculated and was found significant in the nasal, inferior, superior, and temporal segments. Conclusion: RNFL average thickness is not a reliable index for early diagnosis of glaucoma and for the follow-up of patients with ocular hypertension. Segmental RNFL thickness seems to be a more reliable index. Deep structural alterations with OCT examination constitute an important

  16. Recent Advances in Treatments of Primary Focal Segmental Glomerulosclerosis in Children

    PubMed Central

    2016-01-01

    Focal segmental glomerulosclerosis (FSGS) is a nephrotic syndrome. Up to around 80% of cases of primary FSGS are resistant to steroid treatment. A large proportion of patients with steroid-resistant FSGS progress to end-stage renal disease. The purpose of treatment is to obtain a complete remission of proteinuria, a necessary step that precedes improved renal survival and reduces the risk of progression to chronic kidney disease. When this is not possible, the secondary goal is a partial remission of proteinuria. Reduction or remission of proteinuria is the most important factor predictive of renal survival. We will review the current updated strategies for treatment of primary FSGS in children, including traditional therapies consisting of corticosteroids and calcineurin inhibitors and novel therapies such as rituximab, abatacept, adalimumab, and fresolimumab. PMID:27195285

  17. Quantification of Valleys of Randomly Textured Substrates as a Function of Opening Angle: Correlation to the Defect Density in Intrinsic nc-Si:H.

    PubMed

    Kim, Do Yun; Hänni, Simon; Schüttauf, Jan-Willem; van Swaaij, René A C M M; Zeman, Miro

    2016-08-17

    Optical and electrical properties of hydrogenated nanocrystalline silicon (nc-Si:H) solar cells are strongly influenced by the morphology of underlying substrates. By texturing the substrates, the photogenerated current of nc-Si:H solar cells can increase due to enhanced light scattering. These textured substrates are, however, often incompatible with defect-less nc-Si:H growth resulting in lower Voc and FF. In this study we investigate the correlation between the substrate morphology, the nc-Si:H solar-cell performance, and the defect density in the intrinsic layer of the solar cells (i-nc-Si:H). Statistical surface parameters representing the substrate morphology do not show a strong correlation with the solar-cell parameters. Thus, we first quantify the line density of potentially defective valleys of randomly textured ZnO substrates where the opening angle is smaller than 130° (ρ<130). This ρ<130 is subsequently compared with the solar-cell performance and the defect density of i-nc-Si:H (ρdefect), which is obtained by fitting external photovoltaic parameters from experimental results and simulations. We confirm that when ρ<130 increases the Voc and FF significantly drops. It is also observed that ρdefect increases following a power law dependence of ρ<130. This result is attributed to more frequently formed defective regions for substrates having higher ρ<130. PMID:27463965

  18. 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. PMID:22492281

  19. Long-Term Microturbine Exposure of an Advanced Alloy for Microturbine Primary Surface Recuperators

    SciTech Connect

    Matthews, Wendy; More, Karren Leslie; Walker, Larry R

    2009-01-01

    Haynes alloy HR-120 (Haynes and HR-120 are trademarks of Haynes International, Inc.) forms a protective oxide scale when exposed to the harsh operating environment of a microturbine primary surface recuperator. Primary surface recuperators manufactured from HR-120 are currently in use on the Capstone C65 MicroTurbine (MicroTurbine is a registered trademark of Capstone Turbine Corporation). Long-term microturbine tests of this alloy are currently being conducted at an elevated turbine exit temperature ({approx}100 F higher than that in a normal operation) at Capstone Turbine Corporation. Alloy samples that have been tested under steady-state microturbine operating conditions are removed after predetermined exposure intervals for characterization by Capstone Turbine Corporation in collaboration with Oak Ridge National Laboratory. Such evaluations include the characterization of surface oxide scales and the associated alloy compositional changes following a steady-state operation ranging from 1800 h to 14,500 h. Results from the microstructural and compositional analyses of these long-term steady-state engine-tested HR-120 samples are used to illustrate the progression of alloy oxidation in the microturbine operating environment.

  20. 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.

  1. 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.

  2. Advancement of the segment support system for the Thirty Meter Telescope primary mirror

    NASA Astrophysics Data System (ADS)

    Williams, Eric C.; Baffes, Curtis; Mast, Terry; Nelson, Jerry; Platt, Benjamin; Ponchione, R. J.; Ponslet, Eric; Setoodeh, Shahriar; Sirota, Mark; Stephens, Vince; Stepp, Larry; Tubb, Alan

    2008-07-01

    This paper presents refinements to the design of the TMT primary mirror segment passive-support system that are effective in reducing gravity print-through and thermal distortion effects. First, a novel analytical method is presented for tuning the axial and lateral support systems in a manner that results in improved optical performance when subject to varying gravity fields. The method utilizes counterweights attached to the whiffletrees to cancel astigmatic and comatic errors normally resulting when the lateral support system resists transverse loads induced by gravity. Secondly, several central diaphragm designs are presented and analyzed to assess lateral-gravity and thermal distortion performance: 1) a simple flat diaphragm, 2) a stress-relieving diaphragm having a slotted outer rim and a circumferential convolution near the outside diameter, and 3) a flat diaphragm having a slotted outer rim. The latter design is chosen based on results from analytical studies which show it to have better overall optical performance in the presence of gravity and thermal environments.

  3. 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. PMID:25316177

  4. 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. PMID:26276723

  5. 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.

  6. Prospective Randomized Study Comparing Combined Phaco-ExPress and Phacotrabeculectomy in Open Angle Glaucoma Treatment: 12-Month Follow-Up

    PubMed Central

    Konopińska, Joanna; Deniziak, Marta; Saeed, Emil; Bartczak, Agnieszka; Zalewska, Renata; Mariak, Zofia; Rękas, Marek

    2015-01-01

    Purpose of the Study. To compare the efficacy and safety of phacotrabeculectomy (P-Trab) and phacoemulsification with the ExPress (P-ExPress) mini glaucoma shunt implantation. Study Plan. Prospective randomized study. Material and Methods. 85 eyes with cataract and unregulated open angle glaucoma. There were 46 eyes in the P-ExPress and 39 the P-Trab group. Intraocular pressure (IOP), the number of antiglaucoma medications, qualified and complete surgical success (defined as IOP ≤ 18.0 mmHg), visual acuity (CDVA), the number of endothelial cells, and postoperative complications and additional procedures were assessed. Results. After 12 months of observation, the average IOP in the P-Express group went from 26.4 ± 9.3 down to 17.1 ± 5 mmHg (P < 0.05) and from 27.9 ± 12.9 down to 15.9 ± 2.7 mmHg in the P-Trab group (P < 0.05). No significant differences in the amount of medications used after surgery and CDVA were discovered between the groups. In the P-ExPress group, greater loss of endothelial cells was noted (CDloss%), compared to the P-Trab group. Conclusions. Both P-ExPress and P-Trab have comparable efficacy and similar early postoperative complication profile. The presence of additional implant (as is the case of the ExPress mini glaucoma shunt implantation) may cause progressive loss of endothelial cells. PMID:26137318

  7. Association Between Statin Use and Open-angle Glaucoma in Hyperlipidemia Patients: A Taiwanese Population-based Case-control Study.

    PubMed

    Chen, Hsin-Yi; Hsu, Sheng-Yao; Chang, Yue-Cune; Lin, Che-Chen; Sung, Fung-Chang; Chen, Wen-Chi; Kao, Chia-Huang

    2015-11-01

    The aim of the study was to investigate the association between statin use and open-angle glaucoma (OAG) risk in hyperlipidemia patients.We used the research database of the Taiwan National Health Insurance program to conduct a population-based case-control study. A total of 1276 patients with newly diagnosed OAG were identified from 2004 to 2011. Controls comprised of 12,760 patients without glaucoma and were frequency-matched for age, sex, history of diabetes mellitus, and year of hyperlipidemia diagnosis at a 1:10 ratio. Accumulated defined daily doses (DDDs) of statins prescribed during follow-up were calculated. Average statin use was calculated as the sum of DDDs divided by the duration from the initial statin prescription date to the index date (per year), and was subdivided into 3 levels: <30, 30 to 119, and ≥120 DDDs. Comorbidity, including hypertension, depression, and the Charlson comorbidity index, the frequency of eye care visits, and the use of nonstatin cholesterol-lowering drugs, were all considered as confounding factors.For the group with statin use, the adjusted odds ratio of OAG was 1.02 (95% confidence interval 0.90-1.15) when compared with the group without statin use. Subanalysis showed that a high dosage of statin use (≥120 DDD/y) resulted in a1.24-fold increased risk of OAG (odds ratio 1.24, 95% confidence interval 1.03-1.49). The incidence of OAG was increased with the increase of the dosage of statin use (P for trend = 0.0458).Clinicians should be cautious of hyperlipidemia patients with a high dosage of statin use because it might be associated with an increased risk of OAG. Ophthalmologist consultation is necessary for this high-risk group. PMID:26559301

  8. Novel findings in patients with primary hyperoxaluria type III and implications for advanced molecular testing strategies.

    PubMed

    Beck, Bodo B; Baasner, Anne; Buescher, Anja; Habbig, Sandra; Reintjes, Nadine; Kemper, Markus J; Sikora, Przemyslaw; Mache, Christoph; Pohl, Martin; Stahl, Mirjam; Toenshoff, Burkhard; Pape, Lars; Fehrenbach, Henry; Jacob, Dorrit E; Grohe, Bernd; Wolf, Matthias T; Nürnberg, Gudrun; Yigit, Gökhan; Salido, Eduardo C; Hoppe, Bernd

    2013-02-01

    Identification of mutations in the HOGA1 gene as the cause of autosomal recessive primary hyperoxaluria (PH) type III has revitalized research in the field of PH and related stone disease. In contrast to the well-characterized entities of PH type I and type II, the pathophysiology and prevalence of type III is largely unknown. In this study, we analyzed a large cohort of subjects previously tested negative for type I/II by complete HOGA1 sequencing. Seven distinct mutations, among them four novel, were found in 15 patients. In patients of non-consanguineous European descent the previously reported c.700+5G>T splice-site mutation was predominant and represents a potential founder mutation, while in consanguineous families private homozygous mutations were identified throughout the gene. Furthermore, we identified a family where a homozygous mutation in HOGA1 (p.P190L) segregated in two siblings with an additional AGXT mutation (p.D201E). The two girls exhibiting triallelic inheritance presented a more severe phenotype than their only mildly affected p.P190L homozygous father. In silico analysis of five mutations reveals that HOGA1 deficiency is causing type III, yet reduced HOGA1 expression or aberrant subcellular protein targeting is unlikely to be the responsible pathomechanism. Our results strongly suggest HOGA1 as a major cause of PH, indicate a greater genetic heterogeneity of hyperoxaluria, and point to a favorable outcome of type III in the context of PH despite incomplete or absent biochemical remission. Multiallelic inheritance could have implications for genetic testing strategies and might represent an unrecognized mechanism for phenotype variability in PH. PMID:22781098

  9. Advanced TEM characterization of stress corrosion cracking of Alloy 600 in pressurized water reactor primary water environment

    NASA Astrophysics Data System (ADS)

    Sennour, M.; Laghoutaris, P.; Guerre, C.; Molins, R.

    2009-09-01

    Advanced transmission electron microscopy techniques were carried out in order to investigate stress corrosion cracking in Alloy 600 U-bend samples exposed in simulated PWR primary water at 330 °C. Using high-resolution imaging and fine-probe chemical analysis methods, ultrafine size oxides present inside cracks and intergranular attacks were nanoscale characterized. Results revealed predominance of Cr 2O 3 oxide and Ni-rich metal zones at the majority of encountered crack tip areas and at leading edge of intergranular attacks. However, NiO-structure oxide was predominant far from crack tip zones and within cracks propagating along twin boundaries and inside grains. These observations permit to suggest a mechanism for intergranular stress corrosion cracking of Alloy 600 in PWR primary water. Indeed, the results suggest that stress corrosion cracking is depending on chromium oxide growth in the grain boundary. Oxide growth seems to be dependent on oxygen diffusion in porous oxide and chromium diffusion in strained alloy and in grain boundary beyond crack tip. Strain could promote transport kinetic and oxide formation by increasing defaults rate like dislocations.

  10. 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.

  11. 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

  12. 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. PMID:25719471

  13. Metachronous primary uterine cancer surgically resected during Crizotinib treatment in a ALK-rearranged advanced lung adenocarcinoma

    PubMed Central

    Misino, Andrea; Scattone, Anna; Caldarola, Lucia; Petroni, Stella; Logroscino, Antonio; Montagna, Elisabetta Sara; Serio, Gabriella; Simone, Giovanni; Galetta, Domenico

    2016-01-01

    Rearrangements of the anaplastic lymphoma kinase (ALK) gene are present in 3% to 7% of non-small-cell lung cancers (NSCLCs). Patients harboring ALK rearrangements show very favourable outcomes if treated with targeted agents, among which crizotinib is the first and best studied. Crizotinib, an oral small-molecule tyrosine kinase inhibitor of ALK, MET, and ROS1 kinases, is a very active and well tolerated drug. Nevertheless, the optimal therapy management with this new drug is still partially unknown, especially with regard to the safety of combined treatments. Recently, the integration of locoregional treatments has been proposed as a feasible multimodality strategy in selected patients with good clinical conditions and slow-growing or oligoprogressive disease. In this report, a case of advanced lung adenocarcinoma, progressed after first line chemotherapy and re-biopsied detecting ALK rearrangement, is described. During crizotinib treatment the primary lung tumor showed an excellent regression; meanwhile a major surgery for a metachronous uterine cancer was safely and successfully carried out. PMID:26958511

  14. Advanced fracture modeling in the Uinta Basin (Utah) for optimized primary and secondary recovery. Final report, September 1998

    SciTech Connect

    1998-12-01

    The completed study focused on an area fracture-controlled highly unpredictable, fracture-controlled production near the Duchesne Fault Zone, Uinta Basin, in northeastern Utah. Production is seriously influenced by numerous high-angle faults and associated fractures--represented at the surface by a set of parallel, N80{degree}W-trending lineaments, and intricate fracture patterns in outcrop. Specific production is erratic and secondary recovery design is difficult because well-specific structural characterization and local fracture patterns are poorly understood. Furthermore, numerical models to simulate fluid flow in fractured reservoirs were either overly simplistic (did not adequately account for mechanical contrasts between matrix and fractures) or were extremely complex, requiring volumes of data typically not available to the operator. The contractors proposed implementing advanced geological, geomechanical and reservoir engineering methods to recognize and model the complex fracture networks exhibited at the surface and suggested in the shallow subsurface in the Duchesne Fault Zone. The intended methodology was to be developed in a data-limited environment, recognizing that operators in the basin will not have the financial resources or motivation to perform sophisticated and expensive reservoir engineering programs. User-friendly models for permeability, stress, and production using key geological and geophysical data, developed in this study can then be used to determine: economic placement of future operations, assessment of recoverable hydrocarbons, and forecasting of primary and secondary recovery.

  15. Assessment of Open-Angle Glaucoma Peripapillary and Macular Choroidal Thickness Using Swept-Source Optical Coherence Tomography (SS-OCT)

    PubMed Central

    Song, Yong Ju; Kim, Young Kook; Jeoung, Jin Wook; Park, Ki Ho

    2016-01-01

    Objective To compare peripapillary and macular choroidal thickness (PCT and MCT) between open-angle glaucoma (OAG) and normal controls using swept-source optical coherence tomography (SS-OCT), and to evaluate global and localized relationships between choroidal thickness and various factors in OAG, also using SS-OCT. Methods In this cross-sectional comparative study, 134 OAG patients and 73 normal controls were examined. PCT (global, 12 clock-hour sectors), MCT (global, six sectors) were measured by SS-OCT. The difference in choroidal thickness between the OAG patients and the normal controls was analyzed. The relationships between choroidal thickness and various factors including age, sex, spherical equivalent (SE), axial length (AXL), central corneal thickness (CCT), intraocular pressure (IOP), peripapillary retinal nerve fiber layer thickness (pRNFLT), visual field mean deviation (MD), ganglion cell-inner plexiform layer thickness (GCIPLT), and disc area were analyzed by univariate and multivariate linear regression. Global and regional analyses were performed in 12 segments of the peripapillary circle and in six sectors of the macula. Results There were significant differences in global PCT and MCT between the OAG patients and the normal controls (115.22±41.17 vs. 138.89±44.70, P<0.001), (184.36±57.15 vs. 209.25±61.11, P = 0.004). The difference in global PCT remained, both after adjusting for age, AXL (117.08±3.45 vs. 135.47±4.70, P = 0.002) and also after adjusting for age, AXL, disc area (117.46±3.46 vs. 135.67±4.67, P = 0.002). But the difference in global MCT did not remain after adjusting for age, AXL, SE (188.18±4.46 vs. 202.25±6.08, P = 0.066). PCT showed significant differences between the groups in all of the 12 clock-hour sectors. These differences remained after adjusting for age, AXL and for age, AXL, disc area, with the exception of the 10 o’clock (o/c) sector. MCT in six sectors showed differences between the two groups, but they did

  16. 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

  17. Brain response to primary blast wave using validated finite element models of human head and advanced combat helmet.

    PubMed

    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 curves for lung

  18. Mutation status concordance between primary lesions and metastatic sites of advanced non-small-cell lung cancer and the impact of mutation testing methodologies: a literature review.

    PubMed

    Sherwood, James; Dearden, Simon; Ratcliffe, Marianne; Walker, Jill

    2015-01-01

    Increased understanding of the genetic aetiology of advanced non-small-cell lung cancer (aNSCLC) has facilitated personalised therapies that target specific molecular aberrations associated with the disease. Biopsy samples for mutation testing may be taken from primary or metastatic sites, depending on which sample is most accessible, and upon differing diagnostic practices between territories. However, the mutation status concordance between primary tumours and corresponding metastases is the subject of debate. This review aims to ascertain whether molecular diagnostic testing of either the primary or metastatic tumours is equally suitable to determine patient eligibility for targeted therapies. A literature search was performed to identify articles reporting studies of mutations in matched primary and metastatic aNSCLC tumour samples. Clinical results of mutation status concordance between matched primary and metastatic tumour samples from patients with aNSCLC were collated. Articles included in this review (N =26) all reported mutation status data from matched primary and metastatic tumour samples obtained from adult patients with aNSCLC. Generally, substantial concordance was observed between primary and metastatic tumours in terms of EGFR, KRAS, BRAF, p16 and p53 mutations. However, some level of discordance was seen in most studies; mutation testing methodologies appeared to play a key role in this, along with underlying tumour heterogeneity. Substantial concordance in mutation status observed between primary and metastatic tumour sites suggests that diagnostic testing of either tumour type may be suitable to determine a patient's eligibility for personalised therapies. As with all diagnostic testing, highly sensitive and appropriately validated mutation analysis methodologies are desirable to ensure accuracy. Additional work is also required to define how much discordance is clinically significant given natural tumour heterogeneity. The ability of both

  19. Maintenance monotherapy with Gemcitabine following cisplatin-based primary combination chemotherapy in surgically treated advanced urothelial carcinoma: A matched-pair single institution analysis

    PubMed Central

    KALOGIROU, CHARIS; SVISTUNOV, ANDREY; KREBS, MARKUS; LAUSENMEYER, EVA MARIA; VERGHO, DANIEL; RIEDMILLER, HUBERTUS; KOCOT, ARKADIUS

    2016-01-01

    The role of maintenance therapy with Gemcitabine (GEM) following cisplatin-based combination chemotherapy (CBCC) in patients with surgically treated advanced urothelial carcinoma (UC) remains to be fully elucidated. In the present case control study, a retrospective analysis was performed to evaluate the role of GEM monotherapy following surgical intervention for advanced UC. Between 1999 and 2013, 38 patients were identified with surgically treated advanced UC after having completed CBCC, who were additionally treated quarterly with two consecutive GEM (1,250 mg/m2) infusions as maintenance therapy. This collective was matched by propensity score matching to a control collective (n=38) that received primary CBCC alone, and the overall survival (OS), cancer-specific survival (CSS) and progression-free survival (PFS) rates were determined for the two collectives using Kaplan-Meier estimates and the log-rank test. Regression analysis was performed using the Cox proportional hazards model. The median follow-up time was 37 months (interquartile range: 9–148). Interestingly, patients treated with GEM following primary chemotherapy had a significantly improved outcome with respect to the 5-year OS (46.2 vs. 26.4%, P=0.0314) and 5-year CSS (61.3 vs. 33.4%, P=0.0386) rates. Notably, the 5-year PFS rate did not differ between the two groups (10.3 vs. 16.1%, P=0.134). It is proposed that additional GEM maintenance monotherapy is able to improve survival rates following primary CBCC in surgically treated patients with advanced UC, suggesting a possible treatment option for patients with, e.g., unclear disease status, or those who would require an active maintenance therapy in the future. Prospective studies should further determine the impact of GEM monotherapy with respect to PFS rates in groups comprising larger numbers of patients. PMID:27073682

  20. 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.

  1. 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

  2. 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

  3. 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.

  4. 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.

  5. Predictive value of the age-adjusted charlson comorbidity index on perioperative complications and survival in patients undergoing primary debulking surgery for advanced epithelial ovarian cancer

    PubMed Central

    Suidan, Rudy S.; Leitao, Mario M.; Zivanovic, Oliver; Gardner, Ginger J.; Long Roche, Kara C.; Sonoda, Yukio; Levine, Douglas A.; Jewell, Elizabeth L.; Brown, Carol L.; Abu-Rustum, Nadeem R.; Charlson, Mary E.; Chi, Dennis S.

    2016-01-01

    Objective To assess the ability of the Age-Adjusted Charlson Comorbidity index (ACCI) to predict perioperative complications and survival in patients undergoing primary debulking for advanced epithelial ovarian cancer (EOC). Methods Data were analyzed for all patients with stage IIIB-IV EOC who underwent primary cytoreduction from 1/2001–1/2010 at our institution. Patients were divided into 3 groups based on an ACCI of 0–1, 2–3, and ≥4. Clinical and survival outcomes were assessed and compared. Results We identified 567 patients; 199 (35%) had an ACCI of 0–1, 271 (48%) had an ACCI of 2–3, and 97 (17%) had an ACCI of ≥4. The ACCI was significantly associated with the rate of complete gross resection (0–1=44%, 2–3=32%, and ≥4=32%; p=0.02), but was not associated with the rate of minor (47% vs 47% vs 43%, p=0.84) or major (18% vs 19% vs 16%, p=0.8) complications. The ACCI was also significantly associated with progression-free (PFS) and overall survival (OS). Median PFS for patients with an ACCI of 0–1, 2–3, and ≥4 was 20.3, 16, and 15.4 months, respectively (p=0.02). Median OS for patients with an ACCI of 0–1, 2–3, and ≥4 was 65.3, 49.9, and 42.3 months, respectively (p<0.001). On multivariate analysis, the ACCI remained a significant prognostic factor for both PFS (p=0.02) and OS (p<0.001). Conclusions The ACCI was not associated with perioperative complications in patients undergoing primary cytoreduction for advanced EOC, but was a significant predictor of PFS and OS. Prospective clinical trials in ovarian cancer should consider stratifying for an age-comorbidity covariate. PMID:26037900

  6. Hematogenous Splenic Metastases as an Independent Negative Prognosis Factor at the Moment of Primary Cytoreduction in Advanced Stage Epithelial Ovarian Cancer--A Single Center Experience.

    PubMed

    Bacalbasa, Nicolae; Balescu, Irina; Dima, Simona; Brasoveanu, Vladislav; Popescu, Irinel

    2015-10-01

    Ovarian cancer represents an aggressive gynecological malignancy with a high capacity for dissemination. Once the tumor cells go beyond the pelvic area, upper abdominal involvement, including hepatic, diaphragmatic or even splenic, is frequently seen. The aim of the present study was to determine the impact on survival of parenchymatous versus peritoneal splenic metastases versus splenic hilum lymph node involvement at the time of primary cytoreduction for advanced-stage epithelial ovarian cancer. Sixty-six patients with a mean age of 54.12 years (range=25-80 years) were submitted to splenectomy in the context of primary cytoreduction at the Dan Setlacec Center of Gastrointestinal Disease and Liver Transplantation, Fundeni Clinical Institute, between January 2002 and May 2014. Although complete macroscopic resection was attempted in all cases, an R0 resection was achieved only in 57 out of the 66 cases. Histopathological studies confirmed the presence of serous subtype in 61 cases, while in the other five cases, the mucinous subtype was found. When studying the specimens of splenectomy, capsular invasion was found in 35 cases (53%), parenchymatous involvement was present in 19 (28.7%), and hilar involvement was present in 12 (18.1%). The overall morbidity rate was 30%, while the 30-day postoperative mortality rate was 7%. The median overall survival for cases with peritoneal seeding was 58.4 months, while that for patients with parenchymatous involvement was 24.5 months (p=0.0126); patients diagnosed with hilar involvement had a median overall survival of 40.6 months (p=0.362). In conclusion, the presence of parenchymatous splenic metastases at primary cytoreduction for advanced-stage ovarian cancer is associated with significantly poorer survival when compared to hilar or peritoneal seeding. PMID:26408738

  7. Advancing the application of systems thinking in health: South African examples of a leadership of sensemaking for primary health care

    PubMed Central

    2014-01-01

    Background New forms of leadership are required to bring about the fundamental health system changes demanded by primary health care (PHC). Using theory about complex adaptive systems and policy implementation, this paper considers how actors’ sensemaking and the exercise of discretionary power currently combine to challenge PHC re-orientation in the South African health system; and provides examples of leadership practices that promote sensemaking and power use in support of PHC. Methods The paper draws on observational, interview, and reflective data collected as part of the District Innovation and Action Learning for Health Systems Development (DIALHS) project being implemented in Cape Town, South Africa. Undertaken collaboratively between health managers and researchers, the project is implemented through cycles of action-learning, including systematic reflection and synthesis. It includes a particular focus on how local health managers can better support front line facility managers in strengthening PHC. Results The results illuminate how the collective understandings of staff working at the primary level - of their working environment and changes within it – act as a barrier to centrally-led initiatives to strengthen PHC. Staff often fail to take ownership of such initiatives and experience them as disempowering. Local area managers, located between the centre and the service frontline, have a vital role to play in providing a leadership of sensemaking to mediate these challenges. Founded on personal values, such leadership entails, for example, efforts to nurture PHC-aligned values and mind-sets among staff; build relationships and support the development of shared meanings about change; instil a culture of collective inquiry and mutual accountability; and role-model management practices, including using language to signal meaning. Conclusions PHC will only become a lived reality within the South African health system when frontline staff are able to

  8. Environmental and health disparities in residential communities of New Orleans: the need for soil lead intervention to advance primary prevention.

    PubMed

    Mielke, Howard W; Gonzales, Christopher R; Powell, Eric T; Mielke, Paul W

    2013-01-01

    Urban environments are the major sites for human habitation and this study evaluates soil lead (Pb) and blood Pb at the community scale of a U.S. city. There is no safe level of Pb exposure for humans and novel primary Pb prevention strategies are requisite to mitigate children's Pb exposure and health disparities observed in major cities. We produced a rich source of environmental and Pb exposure data for metropolitan New Orleans by combining a large soil Pb database (n=5467) with blood Pb databases (n=55,551 pre-Katrina and 7384 post-Katrina) from the Louisiana Childhood Lead Poisoning Prevention Program (LACLPPP). Reanalysis of pre- and post-Hurricane Katrina soil samples indicates relatively unchanged soil Pb. The objective was to evaluate the New Orleans soil Pb and blood Pb database for basic information about conditions that may merit innovative ways to pursue primary Pb exposure prevention. The city was divided into high (median census tract soil≥100 mg/kg) and low Pb areas (median census tract soil<100mg/kg). Soil and blood Pb concentrations within the high and low Pb areas of New Orleans were analyzed by permutation statistical methods. The high Pb areas are toward the interior of the city where median soil Pb was 367, 313, 1228, and 103 mg/kg, respectively for samples collected at busy streets, residential streets, house sides, and open space locations; the low Pb areas are in outlying neighborhoods of the city where median soil Pb was 64, 46, 32, and 28 mg/kg, respectively for busy streets, residential streets, house sides, and open spaces (P-values<10(-16)). Pre-Katrina children's blood Pb prevalence of ≥5 μg/dL was 58.5% and 24.8% for the high and low Pb areas, respectively compared to post-Katrina prevalence of 29.6% and 7.5%, for high and low Pb areas, respectively. Elevated soil Pb permeates interior areas of the city and children living there generally lack Pb safe areas for outdoor play. Soil Pb medians in outlying areas were safer by

  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. Primary TKI resistance in advanced non-small cell lung cancer with EGFR mutation: an open question.

    PubMed

    Giuliani, Jacopo; Martelli, Salvatore; Remo, Andrea; Bonetti, Andrea

    2015-01-01

    The malignant behavior of non-small cell lung cancer (NSCLC) is caused by different driver mutations, which may include alterations in the epidermal growth factor receptor (EGFR) signaling pathway. Activating mutations in exons 19 or 21 of EGFR in NSCLC are associated with increased sensitivity to EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib. However, approximately 10% of NSCLC patients show primary resistance to TKIs, and the resistance mechanism is poorly understood. We report the case of a 72-year-old nonsmoking Caucasian woman who underwent pulmonary segmentectomy for right peripheral T1N0M0 NSCLC. The tumor was an adenocarcinoma, with a point mutation in exon 21 of EGFR and with negative ALK gene rearrangement. Postoperative CT scan revealed right pleural effusion and abundant ascites without metastases to parenchymal organs. After paracentesis with positive cytology for adenocarcinoma, the patient started therapy with oral gefitinib 250 mg/day. CT scan after 2 months revealed disease progression with an increase in the pleural effusion (right and left) and ascites, as well as the appearance of solid tissue involving the right main bronchus and bronchus intermedius. Gefitinib was stopped and the patient died 1 month later of progressive NSCLC. The peculiarities of our case are the site of the metastatic disease and the complete lack of a response to gefitinib in a patient with an activating mutation in EGFR exon 21. PMID:25953440

  13. Six-Month Progression-Free Survival as the Primary Endpoint to Evaluate the Activity of New Agents as Second-line Therapy for Advanced Urothelial Carcinoma

    PubMed Central

    Agarwal, Neeraj; Bellmunt, Joaquim; Maughan, Benjamin L.; Boucher, Kenneth M.; Choueiri, Toni K.; Qu, Angela Q.; Vogelzang, Nicholas J.; Fougeray, Ronan; Niegisch, Guenter; Albers, Peter; Wong, Yu-Ning; Ko, Yoo-Joung; Sridhar, Srikala S.; Tantravahi, Srinivas K.; Galsky, Matthew D.; Petrylak, Daniel P.; Vaishampayan, Ulka N.; Mehta, Amitkumar N.; Beer, Tomasz M.; Sternberg, Cora. N.; Rosenberg, Jonathan E.; Sonpavde, Guru

    2014-01-01

    This study examined the association of progression-free survival at 6 months with overall survival in the context of second-line therapy of advanced urothelial carcinoma in pooled patient-level data from 10 phase II trials and then externally validated in a large phase III trial. Progression-free survival at 6 months was significantly correlated with overall survival and is an innovative primary endpoint to evaluate new agents in this setting. Objective Second-line systemic therapy for advanced urothelial carcinoma (UC) has substantial unmet needs, and current agents show dismal activity. Second-line trials of metastatic UC have used response rate (RR) and median progression-free survival (PFS) as primary endpoints, which may not reflect durable benefits. A more robust endpoint to identify signals of durable benefits when investigating new agents in second-line trials may expedite drug development. PFS at 6 months (PFS6) is a candidate endpoint, which may correlate with overall survival (OS) at 12 months (OS12) and may be applicable across cytostatic and cytotoxic agents. Methods Ten second-line phase II trials with individual patient outcomes data evaluating chemotherapy or biologics were combined for discovery, followed by external validation in a phase III trial. The relationship between PFS6/RR and OS12 was assessed at the trial level using Pearson correlation and weighted linear regression, and at the individual level using Pearson chi-square test with Yates continuity correction. Results In the discovery dataset, a significant correlation was observed between PFS6 and OS12 at the trial (R2 = 0.55, Pearson correlation = 0.66) and individual levels (82%, Қ = 0.45). Response correlated with OS12 at the individual level less robustly (78%, Қ = 0.36), and the trial level association was not statistically significant (R2 = 0.16, Pearson correlation = 0.37). The correlation of PFS6 (81%, Қ = 0.44) appeared PMID:24220220

  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. Expression of cell cycle markers is predictive of the response to primary systemic therapy of locally advanced breast cancer.

    PubMed

    Tőkés, Tímea; Tőkés, Anna-Mária; Szentmártoni, Gyöngyvér; Kiszner, Gergő; Madaras, Lilla; Kulka, Janina; Krenács, Tibor; Dank, Magdolna

    2016-06-01

    We aimed to analyze to what extent expression of four cell cycle regulation markers-minichromosome maintenance protein (MCM2), Ki-67, cyclin A, and phosphohistone-H3 (PHH3)-predict response to primary systemic therapy in terms of pathological complete remission (pCR). In search of an accurate and reproducible scoring method, we compared computer-assisted (CA) and routine visual assessment (VA) of immunoreactivity. We included 57 patients with breast cancer in the study. The cell cycle markers were detected using immunohistochemistry on pre-therapy core biopsy samples. Parallel CA (validated by manual labeling) and standard VA were performed and compared for diagnostic agreement and predictive value for pCR. CA and VA results were dichotomized based on receiver operating characteristic analysis defined optimal cut-off values. "High" was defined by staining scores above the optimal cut-off, while "low" had staining scores below the optimal cut-off. The CA method resulted in significantly lower values for Ki-67 and MCM2 compared to VA (mean difference, -3.939 and -4.323). Diagnostic agreement was highest for cyclin A and PHH3 (-0.586 and -0.666, respectively). Regardless of the method (CA/VA) used, all tested markers were predictive of pCR. Optimal cut-off-based dichotomization improved diagnostic agreement between the CA and VA methods for every marker, in particular for MCM2 (κ = 1, p < 0.000). Cyclin A displayed excellent agreement (κ = 0.925; p < 0.000), while Ki-67 and PHH3 showed good agreement (κ = 0.789, p < 0.000 and κ = 0.794, p < 0.000, respectively). We found all cell cycle markers (Ki-67, MCM2, cyclin A, and PHH3) predictive of pCR. Diagnostic agreement between CA and VA was better at lower staining scores but improved after optimal cut-off-based dichotomization. PMID:27026269

  17. Correlation of polymorphism C3435T of the MDR-1 gene and the response of primary chemotherapy in women with locally advanced breast cancer.

    PubMed

    Rodrigues, F F O; Santos, R E; Melo, M B; Silva, M A L G; Oliveira, A L; Rozenowicz, R L; Ulson, L B; Aoki, T

    2008-01-01

    Primary chemotherapy is a useful strategy for the treatment of locally advanced breast cancer and therefore allows in vivo evaluation of the action of cytotoxic drugs and the possibility of accomplishing conservative breast surgeries, as well as the early treatment of metastasis. Mechanisms of resistance to the drugs include the action of protein associated with the efflux of drugs from the intracellular environment hindering their activity; one of the most studied proteins is P-glycoprotein codified by the MDR-1 gene. The presence of polymorphisms can determine different physiological actions of these proteins, intervening with the response of the drug's action. We evaluated the presence of single nucleotide polymorphism (SNP) C3435T of the MDR-1 gene and its correlation with the response to primary chemotherapy using the RECIST criteria. Forty-one Brazilian women with stages II and III breast cancer using the PCR-RFLP analysis were evaluated. Thirty-three patients with the SNP genotype (TT and CT) and eight patients with the wild genotype (CC) were found; there was no statistically significant correlation between the diverse genotypes and the clinical and pathological responses according to the Cramer correlation coefficient (V = 0.14). The parameters: nuclear and histological degree, and estrogens, progesterone and c-erb B2 receptors did not demonstrate a statistical correlation with the SNP C3435T. Patients with complete pathological response (12.5%) showed only the polymorphic genotype and not the wild genotype. The characteristics of miscegenation in our population could explain the absence of the characterization of a sub-group of individuals where the presence of the polymorphic genotype influenced the response to the primary chemotherapy. PMID:18393221

  18. 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.

  19. Structural and Functional Brain Changes beyond Visual System in Patients with Advanced Glaucoma

    PubMed Central

    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. PMID:25162716

  20. Process and Outcome Measures among COPD Patients with a Hospitalization Cared for by an Advance Practice Provider or Primary Care Physician

    PubMed Central

    Agarwal, Amitesh; Zhang, Wei; Kuo, YongFang; Sharma, Gulshan

    2016-01-01

    Objectives To examine the process and outcomes of care of COPD patients by Advanced Practice Providers (APPs) and primary care physicians. Methods We conducted a cross sectional retrospective cohort study of Medicare beneficiaries with COPD who had at least one hospitalization in 2010. We examined the process measures of receipt of spirometry evaluation, influenza and pneumococcal vaccine, use of COPD medications, and referral to a pulmonary specialist visit. Outcome measures were emergency department (ER) visit, number of hospitalizations and 30-day readmission in 2010. Results A total of 7,257 Medicare beneficiaries with COPD were included. Of these, 1,999 and 5,258 received primary care from APPs and primary care physicians, respectively. Patients in the APP group were more likely to be white, younger, male, residing in non-metropolitan areas and have fewer comorbidities. In terms of process of care measures, APPs were more likely to prescribe short acting bronchodilators (adjusted odds ratio [aOR] = 1.18, 95%Confidence Interval [CI] 1.05–1.32), oxygen therapy (aOR = 1.25, 95% CI 1.12–1.40) and consult a pulmonary specialist (aOR = 1.39, 95% CI 1.23–1.56), but less likely to give influenza and pneumococcal vaccinations. Patients receiving care from APPs had lower rates of ER visits for COPD (aOR = 0.84, 95%CI 0.71–0.98) and had a higher follow-up rate with pulmonary specialist within 30 days of hospitalization for COPD (aOR = 1.25, 95%CI 1.07–1.48) than those cared for by physicians. Conclusions Compared to patients cared for by physicians, patients cared for by APPs were more likely to receive short acting bronchodilator, oxygen therapy and been referred to pulmonologist, however they had lower rates of vaccination probably due to lower age group. Patients cared for by APPs were less like to visit an ER for COPD compared to patients care for by physicians, conversely there was no differences in hospitalization or readmission for COPD between MDs and

  1. 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. PMID:18413959

  2. 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

  3. 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. PMID:16553166

  4. A phase I/II study of leucovorin, carboplatin and 5-fluorouracil (LCF) in patients with carcinoma of unknown primary site or advanced oesophagogastric/pancreatic adenocarcinomas.

    PubMed Central

    Rigg, A.; Cunningham, D.; Gore, M.; Hill, M.; O'Brien, M.; Nicolson, M.; Chang, J.; Watson, M.; Norman, A.; Hill, A.; Oates, J.; Moore, H.; Ross, P.

    1997-01-01

    Carcinoma of unknown primary site (CUPS) accounts for 5-10% of all malignancies. Forty patients with metastatic CUPS or advanced oesophagogastric/pancreatic adenocarcinomas were recruited. Eligibility included ECOG performance status 0-2, minimum life expectancy of 3 months and measurable disease. The regimen consisted of bolus intravenous 5 fluorouracil (5-FU) and leucovorin (20 mg m-2) days 1-5 and carboplatin (AUC5) on day 3. The leucovorin/carboplatin/5-FU (LCF) was repeated every 4 weeks. The starting dose of 5-FU was 350 mg m-2 day-1 with escalation to 370 and then 400 mg m-2 day -1 after the toxicity at the previous level had been assessed. The maximum tolerated dose (MTD) was defined as the dosage of 5-FU that achieved 60% grade 3/4 toxicity. In addition, objective and symptomatic responses, quality of life and survival were assessed. The MTD of 5-FU in the LCF regimen was 370 mg m-2. The predominant toxicity was asymptomatic marrow toxicity. The 350 mg m-2 level was then expanded. There were two toxic deaths due to neutropenic sepsis, one at 370 mg m-2 after one course and one at 350 mg m-2 after four courses. The objective response rate was 25% with one complete response (CR) and nine partial responses (PRs). The median duration of response was 3.4 months (range 1-10). The CR and eight of the nine PRs were in CUPS patients. Twelve patients developed progressive disease on LCF. Median survival for all 40 patients was 7.8 months (10 months median survival for those treated at 350 mg m-2). The majority of patients described a symptomatic improvement with LCF chemotherapy. The recommended dose of 5-FU for future studies is 350 mg m-2 combined with leucovorin 20 mg m-2 and carboplatin (AUC5). PMID:9000605

  5. Single-port or Classic Laparoscopy Compared With Laparotomy to Assess the Peritoneal Cancer Index in Primary Advanced Epithelial Ovarian Cancer.

    PubMed

    Bresson, Lucie; Allard-Duclercq, Clemence; Narducci, Fabrice; Tresch, Emmanuelle; Lesoin, Anne; Ahmeidi, Abesse; Leblanc, Eric

    2016-01-01

    A thorough laparoscopic assessment of the abdominopelvic cavity is a crucial step in the workup of primary advanced epithelial ovarian cancer to decide whether up-front cytoreductive surgery or neoadjuvant chemotherapy is the best option for adequate management. The purpose of our study was to compare single-port laparoscopy (SPL), classic laparoscopy (CL), and laparotomy using the peritoneal cancer index (PCI). Patients treated for Fédération Internationale de Gynécologie et d'Obstétrique stage 3 or 4 epithelial ovarian cancer were included in our study when they underwent a PCI evaluation by laparoscopy followed by laparotomy for cytoreduction. According to the technique used for the "noninvasive" procedure (SPL vs CL), 2 groups were compared retrospectively. The individual records of all patients were reviewed and analyzed. From 2011 to 2014, 21 patients were assessed for PCI by SPL plus laparotomy versus 21 by CL plus laparotomy. The clinicopathological features were similar in both groups (not significant [NS]), except for performance status >0, which was more frequent in the SPL group (39% vs 6%, p = .04). Quotation of PCI was possible for all patients. Nonbrowsing areas marked 3 procedures in the SPL group and 2 procedures in the CL group (NS). The mean PCI score and the score of each region assessed by SPL and CL were comparable with the evaluation by laparotomy (NS). Completeness of cytoreduction was achieved in 78% of cases in both groups (NS). SPL and widely mini-invasive procedures seem to be effective tools compared with laparotomy to adequately assess the resectability of a peritoneal carcinomatosis using the PCI. PMID:27068278

  6. 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

  7. 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

    2016-03-31

    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

  8. 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.

  9. Belinostat in Treating Patients With Advanced Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer or Ovarian Low Malignant Potential Tumors

    ClinicalTrials.gov

    2013-04-11

    Fallopian Tube Cancer; Primary Peritoneal Cavity Cancer; Recurrent Borderline Ovarian Surface Epithelial-stromal Tumor; Recurrent Ovarian Epithelial Cancer; Stage III Borderline Ovarian Surface Epithelial-stromal Tumor; Stage III Ovarian Epithelial Cancer; Stage IV Borderline Ovarian Surface Epithelial-stromal Tumor; Stage IV Ovarian Epithelial Cancer

  10. Comparison of the Prognostic Value of F-18 Pet Metabolic Parameters of Primary Tumors and Regional Lymph Nodes in Patients with Locally Advanced Cervical Cancer Who Are Treated with Concurrent Chemoradiotherapy

    PubMed Central

    Chong, Gun Oh; Jeong, Shin Young; Park, Shin-Hyung; Lee, Yoon Hee; Lee, Sang-Woo; Hong, Dae Gy; Kim, Jae-Chul; Lee, Yoon Soon; Cho, Young Lae

    2015-01-01

    Objective This study investigated the metabolic parameters of primary tumors and regional lymph nodes, as measured by pre-treatment F-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) to compare the prognostic value for the prediction of tumor recurrence. This study also identified the most powerful parameter in patients with locally advanced cervical cancer treated with concurrent chemoradiotherapy. Methods Fifty-six patients who were diagnosed with cervical cancer with pelvic and/or paraaortic lymph node metastasis were enrolled in this study. Metabolic parameters including the maximum standardized uptake value (SUVmax), the metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumors and lymph nodes were measured by pre-treatment F-18 FDG PET/CT. Univariate and multivariate analyses for disease-free survival (DFS) were performed using the clinical and metabolic parameters. Results The metabolic parameters of the primary tumors were not associated with DFS. However, DFS was significantly longer in patients with low values of nodal metabolic parameters than in those with high values of nodal metabolic parameters. A univariate analysis revealed that nodal metabolic parameters (SUVmax, MTV and TLG), paraaortic lymph node metastasis, and post-treatment response correlated significantly with DFS. Among these parameters, nodal SUVmax (hazard ratio [HR], 4.158; 95% confidence interval [CI], 1.1–22.7; p = 0.041) and post-treatment response (HR, 7.162; 95% CI, 1.5–11.3; p = 0.007) were found to be determinants of DFS according to a multivariate analysis. Only nodal SUVmax was an independent pre-treatment prognostic factor for DFS, and the optimal cutoff for nodal SUVmax to predict progression was 4.7. Conclusion Nodal SUVmax according to pre-treatment F-18 FDG PET/CT may be a prognostic biomarker for the prediction of disease recurrence in patients with locally advanced cervical cancer. PMID:26368542

  11. 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

  12. A new primary cleft lip repair technique tailored for Asian patients that combines three surgical concepts: Comparison with rotation--advancement and straight-line methods.

    PubMed

    Funayama, Emi; Yamamoto, Yuhei; Furukawa, Hiroshi; Murao, Naoki; Shichinohe, Ryuji; Hayashi, Toshihiko; Oyama, Akihiko

    2016-01-01

    Various techniques have been described for unilateral cleft lip repair. These may be broadly classified into three types of procedure/concept: the straight-line method (SL; Rose-Thompson effect); rotation-advancement (RA; upper-lip Z-plasty); and the triangular flap method (TA; lower-lip Z-plasty). Based on these procedures, cleft lip repair has evolved in recent decades. The cleft lip repair method in our institution has also undergone several changes. However, we have found that further modifications are needed for Asian patients who have wider philtral dimples and columns than Caucasians, while following the principles of the original techniques mentioned above. Here, we have incorporated the advantages of each procedure and propose a refined hybrid operating technique, seeking a more appropriate procedure for Asian patients. To evaluate our new technique, a comparison study was performed to evaluate RA, SL, and our technique. We have used our new technique to treat 137 consecutive cleft lip cases of all types and degrees of severity, with or without a cleft palate, since 2009. In the time since we adopted the hybrid technique, we have observed improved esthetics of the repaired lip. Our technique demonstrated higher glance impression average scores than RA/SL. PMID:26653337

  13. 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.

  14. Opposing Roles of Membrane and Soluble Forms of the Receptor for Advanced Glycation End Products in Primary Respiratory Syncytial Virus Infection

    PubMed Central

    Miller, Allison L.; Sims, Gary P.; Brewah, Yambasu A.; Rebelatto, Marlon C.; Kearley, Jennifer; Benjamin, Ebony; Keller, Ashley E.; Brohawn, Philip; Herbst, Ronald; Coyle, Anthony J.; Kolbeck, Roland

    2012-01-01

    Respiratory syncytial virus (RSV), a common respiratory pathogen in infants and the older population, causes pulmonary inflammation and airway occlusion that leads to impairment of lung function. Here, we have established a role for receptor for advanced glycation end products (RAGE) in RSV infection. RAGE-deficient (ager−/−) mice were protected from RSV-induced weight loss and inflammation. This protection correlated with an early increase in type I interferons, later decreases in proinflammatory cytokines, and a reduction in viral load. To assess the contribution of soluble RAGE (sRAGE) to RSV-induced disease, wild-type and ager−/− mice were given doses of sRAGE following RSV infection. Of interest, sRAGE treatment prevented RSV-induced weight loss and neutrophilic inflammation to a degree similar to that observed in ager−/− mice. Our work further elucidates the roles of RAGE in the pathogenesis of respiratory infections and highlights the opposing roles of membrane and sRAGE in modulating the host response to RSV infection. PMID:22262795

  15. Recent advances in the utility and use of the General Practice Research Database as an example of a UK Primary Care Data resource

    PubMed Central

    van Staa, Tjeerd; Puri, Shivani; Eaton, Susan

    2012-01-01

    Since its inception in the mid-1980s, the General Practice Research Database (GPRD) has undergone many changes but remains the largest validated and most utilised primary care database in the UK. Its use in pharmacoepidemiology stretches back many years with now over 800 original research papers. Administered by the Medicines and Healthcare products Regulatory Agency since 2001, the last 5 years have seen a rebuild of the database processing system enhancing access to the data, and a concomitant push towards broadening the applications of the database. New methodologies including real-world harm–benefit assessment, pharmacogenetic studies and pragmatic randomised controlled trials within the database are being implemented. A substantive and unique linkage program (using a trusted third party) has enabled access to secondary care data and disease-specific registry data as well as socio-economic data and death registration data. The utility of anonymised free text accessed in a safe and appropriate manner is being explored using simple and more complex techniques such as natural language processing. PMID:25083228

  16. 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.

  17. 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.

  18. 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

  19. Evaluation of functional integrity of the retinohypothalamic tract in advanced glaucoma using multifocal electroretinography and light-induced melatonin suppression.

    PubMed

    Pérez-Rico, Consuelo; de la Villa, Pedro; Arribas-Gómez, Ignacio; Blanco, Román

    2010-11-01

    The aim of the study was to investigate the survival of melanopsin-expressing retinal ganglion cells (mRGCs) and the functional integrity of the retinohypothalamic tract in patients with bilateral advanced glaucomatous optic neuropathy by measuring the neuroendocrine light response of the pineal gland. Nine patients with bilateral advanced primary open-angle glaucoma (glaucoma group) and nine normal control subjects (control group) were included in this pilot observational, prospective, case-control study. The best-corrected visual acuity logMAR, standard automated perimetry mean deviation, and the retinal nerve fiber layer thickness determined by optical coherence tomography and multifocal electroretinography were used to evaluate the changes. Melatonin was analyzed in the saliva by radioimmunoassay before and after exposure to bright light (600 lux) for 60 min at night. The advanced glaucoma group did not have any significant nocturnal melatonin suppression after exposure to bright light (14.28 ± 3.07 pg/ml pre-light melatonin concentration vs. 15.22 ± 3.56 pg/ml after light exposure; p = 0.798) unlike the marked melatonin suppression in the control group (22.43 ± 4.37 pg/ml pre-light melatonin concentration vs. 11.25 ± 1.89 pg/ml after light exposure; p < 0.002). Response density estimates by the scalar product amplitude measure for the interval 0-80 ms of the first-order kernel responses were similar in both groups, indicating that outer retinal function was significantly unchanged in the glaucoma group (5.95 ± 0.54 nV/dg^2) compared with the control group (6.20 ± 0.22 nV/dg^2) (p = 0.689). Our findings are consistent with the interpretation that the rhythmic secretion of melatonin was affected in advanced glaucoma, suggesting that attention should be paid to non-image-forming visual functions, such as control of circadian rhythm and the clinical impact in patients with glaucoma. PMID:20692255

  20. Chinese Herbal Formulation PHY906 and Sorafenib Tosylate in Treating Patients With Advanced Liver Cancer

    ClinicalTrials.gov

    2016-06-17

    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. Syphilis - primary

    MedlinePlus

    Primary syphilis; Secondary syphilis; Late syphilis; Tertiary syphilis ... Syphilis is a sexually transmitted, infectious disease caused by the spirochete bacterium Treponema pallidum . This bacterium causes ...

  2. 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…

  3. Management of patients with chronic open angle glaucoma.

    PubMed

    Stainsby, Helen

    2016-05-11

    Glaucoma refers to a group of conditions that can cause sight loss as a result of damage to the optic nerve head. Glaucoma can affect a person's life in many ways. Healthcare professionals have an important role in educating and supporting patients to manage their condition and adhere to their glaucoma management regimens. Since patients with glaucoma may have additional health conditions, healthcare professionals should have an understanding of glaucoma and the importance of continuing treatment, so that they can facilitate care effectively. PMID:27206206

  4. Primary thrombocythemia

    MedlinePlus

    ... in which the bone marrow produces too many platelets. Platelets are a part of the blood that aids ... Primary thrombocythemia is caused by the overproduction of platelets. If untreated, this condition gets worse over time. ...

  5. Conjunctival TGF-B Level in Primary Augmented Trabeculectomy

    PubMed Central

    Ng, Guan Fook; Raihan, Ishak Siti; Azhany, Yaakub; Maraina, Che Hussin Che; Banumathi, K. Gurusamy; Liza-Sharmini, Tajudin

    2015-01-01

    Purpose : To compare the levels of conjunctival transforming growth factor beta (TGF-β) between glaucoma and control patients and to determine conjunctival TGF-β levels before and 3 months after augmented primary trabeculectomy. Methods : Patients with primary open angle glaucoma (POAG) or primary angle closure glaucoma (PACG) admitted for mitomycin (MMC) augmented primary trabeculectomy due to failure in achieving target pressure after maximum medical therapy were selected. Age-matched non-glaucoma patients were controls. Impression cytology of the conjunctiva was obtained twice from glaucoma patients (1 week before augmented primary trabeculectomy and 3 months after surgery) and once from controls. Conjunctival cells were tagged with an anti-TGF-β antibody and analyzed by flow cytometry. Results : Eighteen patients (11 POAG and 7 PACG patients) and 18 age-matched control patients were included. Conjunctival TGF-β levels were significantly different between glaucoma (35.21% ± 14.12%) and control patients (14.96% ± 6.34%) (p = 0.001). There was a significant reduction in conjunctival TGF-β levels after augmented trabeculectomy (23.0% ± 13.8%) (p < 0.001). A significantly greater reduction in conjunctival TGF-β levels (61.6% ± 17.9%) was associated with complete success of trabeculectomy at 3 months (83.3%) after surgical intervention (p = 0.029). Conclusion : The reduction of TGF-β on the conjunctival post primary augmented trabeculectomy may suggest TGF-β as potential predicting marker of short term trabeculectomy success. However, the result may be affected by site of impression, topical pressure lowering drugs and small sample size. PMID:26401171

  6. Advanced energy storage for space applications: A follow-up

    NASA Technical Reports Server (NTRS)

    Halpert, Gerald; Surampudi, Subbarao

    1994-01-01

    Viewgraphs on advanced energy storage for space applications are presented. Topics covered include: categories of space missions using batteries; battery challenges; properties of SOA and advanced primary batteries; lithium primary cell applications; advanced rechargeable battery applications; present limitations of advanced battery technologies; and status of Li-TiS2, Ni-MH, and Na-NiCl2 cell technologies.

  7. Primary hyperparathyroidism

    PubMed Central

    Pallan, Shelley; Khan, Aliya

    2011-01-01

    Abstract Objective To discuss the presentation, diagnosis, and management of primary hyperparathyroidism (PHPT) in family medicine. Quality of evidence MEDLINE was searched from 2002 to 2009 using the terms presentation, diagnosis, and treatment of PHPT. Proceedings and guidelines from the Third International Workshop on Primary Hyperparathyroidism in May 2008 were reviewed in detail. Most studies offered level II and III evidence, although there were a number of single randomized controlled trials on PHPT (level I evidence). References from pertinent papers were also searched for relevant articles. Articles most relevant to family medicine and primary care practitioners are presented. Main message Primary hyperparathyroidism is the most common cause of hypercalcemia in outpatients. In the Western world, most patients with PHPT present with nonspecific symptoms such as fatigue, mood disturbances, and cognitive impairments. Diagnosis is established when intact parathyroid hormone levels are elevated or at the high end of the normal range in the setting of elevated total or ionized calcium levels (following exclusion of conditions that can mimic PHPT). Criteria for surgery have recently been modified. Surgery is always a suitable option in those with symptomatic PHPT and no contraindications. Those with contraindications or with asymptomatic PHPT not meeting the criteria for surgery can generally be safely monitored and considered for medical management. This might include treatment with bisphosphonates, hormone replacement therapy, raloxifene, or calcimimetic agents; however, there are currently no fracture data for any of these options. Conclusion The definitive therapy for symptomatic and asymptomatic PHPT is parathyroidectomy. In patients with asymptomatic PHPT not meeting the criteria for surgery, monitoring is safe and medical management designed to target skeletal protection or lower serum calcium is a suitable option. PMID:21321169

  8. 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. PMID:27514592

  9. 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

  10. 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,…

  11. 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.

  12. 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."

  13. Interaction of palliative care and primary care.

    PubMed

    Ghosh, Amrita; Dzeng, Elizabeth; Cheng, M Jennifer

    2015-05-01

    Primary care physicians are often the first medical providers patients seek out, and are in an excellent position to provide primary palliative care. Primary palliative care encompasses basic skills including basic evaluation and management of symptoms and discussions about goals of care and advance care planning. Specialty palliative care consultation complements primary care by assisting with complex psychosocial-spiritual patient and family situations. This article reviews primary palliative care skill sets and criteria for when to consider referring patients to specialty palliative care and hospice services. PMID:25920056

  14. 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

  15. Diagnostic Methods in Primary Ciliary Dyskinesia.

    PubMed

    Lucas, Jane S; Paff, Tamara; Goggin, Patricia; Haarman, Eric

    2016-03-01

    Diagnosing primary ciliary dyskinesia is difficult. With no reference standard, a combination of tests is needed; most tests require expensive equipment and specialist scientists. We review the advances in diagnostic testing over the past hundred years, with emphasis on recent advances. We particularly focus on use of high-speed video analysis, transmission electron microscopy, nasal nitric oxide and genetic testing. We discuss the international efforts that are in place to advance the evidence base for diagnostic tests. PMID:26362507

  16. Primary hyperparathyroidism.

    PubMed

    Bilezikian, John P; Cusano, Natalie E; Khan, Aliya A; Liu, Jian-Min; Marcocci, Claudio; Bandeira, Francisco

    2016-01-01

    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

  17. PET-CT in Determining the Radioembolization Dose Delivered to Patients With Liver Metastasis, Primary Liver Cancer, or Biliary Cancer

    ClinicalTrials.gov

    2016-03-01

    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

  18. The Pilot Training Study: Advanced Pilot Training.

    ERIC Educational Resources Information Center

    Kennedy, P. J.

    An overview is presented of advanced pilot training and of the formal advanced pilot training program that constitutes the primary means of providing this training. Section I deals with the various phases of advanced pilot training that a pilot may encounter during his career; Section II deals with the types of aircraft that require some form of…

  19. Primary immunodeficiency

    PubMed Central

    2011-01-01

    Primary immunodeficiency disorder (PID) refers to a heterogeneous group of over 130 disorders that result from defects in immune system development and/or function. PIDs are broadly classified as disorders of adaptive immunity (i.e., T-cell, B-cell or combined immunodeficiencies) or of innate immunity (e.g., phagocyte and complement disorders). Although the clinical manifestations of PIDs are highly variable, most disorders involve at least an increased susceptibility to infection. Early diagnosis and treatment are imperative for preventing significant disease-associated morbidity and, therefore, consultation with a clinical immunologist is essential. PIDs should be suspected in patients with: recurrent sinus or ear infections or pneumonias within a 1 year period; failure to thrive; poor response to prolonged use of antibiotics; persistent thrush or skin abscesses; or a family history of PID. Patients with multiple autoimmune diseases should also be evaluated. Diagnostic testing often involves lymphocyte proliferation assays, flow cytometry, measurement of serum immunoglobulin (Ig) levels, assessment of serum specific antibody titers in response to vaccine antigens, neutrophil function assays, stimulation assays for cytokine responses, and complement studies. The treatment of PIDs is complex and generally requires both supportive and definitive strategies. Ig replacement therapy is the mainstay of therapy for B-cell disorders, and is also an important supportive treatment for many patients with combined immunodeficiency disorders. The heterogeneous group of disorders involving the T-cell arm of the adaptive system, such as severe combined immunodeficiency (SCID), require immune reconstitution as soon as possible. The treatment of innate immunodeficiency disorders varies depending on the type of defect, but may involve antifungal and antibiotic prophylaxis, cytokine replacement, vaccinations and bone marrow transplantation. This article provides a detailed overview

  20. Primary hyperoxalurias: diagnosis and treatment.

    PubMed

    Ben-Shalom, Efrat; Frishberg, Yaacov

    2015-10-01

    Primary hyperoxalurias (PH) comprise a group of three distinct metabolic diseases caused by derangement of glyoxylate metabolism in the liver. Recent years have seen advances in several aspects of PH research. This paper reviews current knowledge of the genetic and biochemical basis of PH, the specific epidemiology and clinical presentation of each type, and therapeutic approaches in different disease stages. Potential future specific therapies are discussed. PMID:25519509

  1. Primary duodenal carcinoma.

    PubMed Central

    Adedeji, O. A.; Trescoli-Serrano, C.; Garcia-Zarco, M.

    1995-01-01

    Eight cases of primary duodenal carcinoma in a district general hospital are presented. The cases highlight the advanced state of the disease at presentation, the difficulty in diagnosis, and its poor prognosis. Duodenal carcinoma occurs in both sexes worldwide with no predisposing factors in the majority of cases. There is an increased risk in patients with familial adenomatous polyposis and adenomas of the duodenum. Duodenal carcinoma occurs about 22 years from the diagnosis of familial adenomatous polyposis in about 2% of patients, forming over 50% of upper gastrointestinal cancers occurring in these patients. Carcinomatous changes occur in 30 to 60% of duodenal villous adenomas and much less in tubulo-villous and tubular adenomas. These categories of patients should be screened and adequately followed up. Aggressive and radical surgery, even in the presence of locally advanced disease and lymph node involvement, gives a better outcome. When curative surgery is not possible, chemotherapy must accompany palliation with or without radiotherapy. Pre-operative chemotherapy may facilitate a curative radical resection. The general five-year survival is 17-33% but some centres have achieved a five-year survival of 40-60% with aggressive management of these patients. PMID:7644397

  2. Advanced drilling systems study

    SciTech Connect

    Pierce, K.G.; Livesay, B.J.

    1995-03-01

    This work was initiated as part of the National Advanced Drilling and Excavation Technologies (NADET) Program. It is being performed through joint finding from the Department of Energy Geothermal Division and the Natural Gas Technology Branch, Morgantown Energy Technology Center. Interest in advanced drilling systems is high. The Geothermal Division of the Department of Energy has initiated a multi-year effort in the development of advanced drilling systems; the National Research Council completed a study of drilling and excavation technologies last year; and the MIT Energy Laboratory recently submitted a proposal for a national initiative in advanced drilling and excavation research. The primary reasons for this interest are financial. Worldwide expenditures on oil and gas drilling approach $75 billion per year. Also, drilling and well completion account for 25% to 50% of the cost of producing electricity from geothermal energy. There is incentive to search for methods to reduce the cost of drilling. Work on ideas to improve or replace rotary drilling technology dates back at least to the 1930`s. There was a significant amount of work in this area in the 1960`s and 1970`s; and there has been some continued effort through the 1980`s. Undoubtedly there are concepts for advanced drilling systems that have yet to be studied; however, it is almost certain that new efforts to initiate work on advanced drilling systems will build on an idea or a variation of an idea that has already been investigated. Therefore, a review of previous efforts coupled with a characterization of viable advanced drilling systems and the current state of technology as it applies to those systems provide the basis for the current study of advanced drilling.

  3. Advance directives

    PubMed Central

    O’Sullivan, Rory; Mailo, Kevin; Angeles, Ricardo; Agarwal, Gina

    2015-01-01

    Abstract Objective To establish the prevalence of patients with advance directives in a family practice, and to describe patients’ perspectives on a family doctor’s role in initiating discussions about advance directives. Design A self-administered patient questionnaire. Setting A busy urban family medicine teaching clinic in Hamilton, Ont. Participants A convenience sample of adult patients attending the clinic over the course of a typical business week. Main outcome measures The prevalence of advance directives in the patient population was determined, and the patients’ expectations regarding the role of their family doctors were elucidated. Results The survey population consisted of 800 participants (a response rate of 72.5%) well distributed across age groups; 19.7% had written advance directives and 43.8% had previously discussed the topic of advance directives, but only 4.3% of these discussions had occurred with family doctors. In 5.7% of cases, a family physician had raised the issue; 72.3% of respondents believed patients should initiate the discussion. Patients who considered advance directives extremely important were significantly more likely to want their family doctors to start the conversation (odds ratio 3.98; P < .05). Conclusion Advance directives were not routinely addressed in the family practice. Most patients preferred to initiate the discussion of advance directives. However, patients who considered the subject extremely important wanted their family doctors to initiate the discussion. PMID:25873704

  4. Primary Progressive Aphasia and Apraxia of Speech

    PubMed Central

    Jung, Youngsin; Duffy, Joseph R.; Josephs, Keith A.

    2014-01-01

    Primary progressive aphasia is a neurodegenerative syndrome characterized by progressive language dysfunction. The majority of primary progressive aphasia cases can be classified into three subtypes: non-fluent/agrammatic, semantic, and logopenic variants of primary progressive aphasia. Each variant presents with unique clinical features, and is associated with distinctive underlying pathology and neuroimaging findings. Unlike primary progressive aphasia, apraxia of speech is a disorder that involves inaccurate production of sounds secondary to impaired planning or programming of speech movements. Primary progressive apraxia of speech is a neurodegenerative form of apraxia of speech, and it should be distinguished from primary progressive aphasia given its discrete clinicopathological presentation. Recently, there have been substantial advances in our understanding of these speech and language disorders. Here, we review clinical, neuroimaging, and histopathological features of primary progressive aphasia and apraxia of speech. The distinctions among these disorders will be crucial since accurate diagnosis will be important from a prognostic and therapeutic standpoint. PMID:24234355

  5. 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.

  6. Advanced access appointments

    PubMed Central

    Hudec, John C.; MacDougall, Steven; Rankin, Elaine

    2010-01-01

    ABSTRACT OBJECTIVE To examine the effects of advanced access (same-day physician appointments) on patient and provider satisfaction and to determine its association with other variables such as physician income and patient emergency department use. DESIGN Patient satisfaction survey and semistructured interviews with physicians and support staff; analysis of physician medical insurance billings and patient emergency department visits. SETTING Cape Breton, NS. PARTICIPANTS Patients, physicians, and support staff of 3 comparable family physician practices that had not implemented advanced access and an established advanced access practice. MAIN OUTCOME MEASURES Self-reported provider and patient satisfaction, physician office income, and patients’ emergency department use. RESULTS The key benefits of implementation of advanced access were an increase in provider and patient satisfaction levels, same or greater physician office income, and fewer less urgent (triage level 4) and nonurgent (triage level 5) emergency department visits by patients. CONCLUSION Currently within the Central Cape Breton Region, 33% of patients wait 4 or more days for urgent appointments. Findings from this study can be used to enhance primary care physician practice redesign. This research supports many benefits of transitioning to an advanced access model of patient booking. PMID:20944024

  7. 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.

  8. 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.

  9. Lapatinib in Treating Patients With Locally Advanced or Metastatic Biliary Tract or Liver Cancer That Cannot Be Removed By Surgery

    ClinicalTrials.gov

    2014-12-18

    Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer

  10. A Novel Missense Mutation in ADAMTS10 in Norwegian Elkhound Primary Glaucoma

    PubMed Central

    Ahonen, Saija J.; Kaukonen, Maria; Nussdorfer, Forrest D.; Harman, Christine D.; Komáromy, András M.; Lohi, Hannes

    2014-01-01

    Primary glaucoma is one of the most common causes of irreversible blindness both in humans and in dogs. Glaucoma is an optic neuropathy affecting the retinal ganglion cells and optic nerve, and elevated intraocular pressure is commonly associated with the disease. Glaucoma is broadly classified into primary open angle (POAG), primary closed angle (PCAG) and primary congenital glaucoma (PCG). Human glaucomas are genetically heterogeneous and multiple loci have been identified. Glaucoma affects several dog breeds but only three loci and one gene have been implicated so far. We have investigated the genetics of primary glaucoma in the Norwegian Elkhound (NE). We established a small pedigree around the affected NEs collected from Finland, US and UK and performed a genome-wide association study with 9 cases and 8 controls to map the glaucoma gene to 750 kb region on canine chromosome 20 (praw = 4.93×10−6, pgenome = 0.025). The associated region contains a previously identified glaucoma gene, ADAMTS10, which was subjected to mutation screening in the coding regions. A fully segregating missense mutation (p.A387T) in exon 9 was found in 14 cases and 572 unaffected NEs (pFisher = 3.5×10−27) with a high carrier frequency (25.3%). The mutation interrupts a highly conserved residue in the metalloprotease domain of ADAMTS10, likely affecting its functional capacity. Our study identifies the genetic cause of primary glaucoma in NEs and enables the development of a genetic test for breeding purposes. This study establishes also a new spontaneous canine model for glaucoma research to study the ADAMTS10 biology in optical neuropathy. PMID:25372548

  11. Tobacco cessation education for advanced practice nurses.

    PubMed

    Whitehead, Diane; Zucker, Steven B; Stone, Jennifer

    2014-01-01

    The predicted shortfall of primary care physicians and the millions of newly insured beginning in 2014 call for an increase in the number of advanced practice nurses (APRNs). Advanced practice nurses can significantly improve their clients' quality of life and increase their life expectancy through tobacco cessation education. The purpose of this study was to educate APRN students on smoking information and techniques to assist clients with quitting smoking in the primary care setting. PMID:24867074

  12. 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.

  13. 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.

  14. Managing Primary Angle Closure Glaucoma – The Role of Lens Extraction in this Era

    PubMed Central

    Baig, Nafees; Kam, Ka-Wai; Tham, Clement C.Y.

    2016-01-01

    Trabeculectomy has been the gold standard in reducing intraocular pressure (IOP) in glaucoma patients, no matter it is angle closure or open angle glaucoma. However in primary angle closure glaucoma, no matter the lens is cataractous or not, it is likely to be pathological, this thicker than usual lens, with or without a more anterior position, is often regarded as a strong contributing factor to angle closure. Lens extraction, no matter it is cataractous or clear, can theoretically eliminate this anatomical predisposing factor of angle closure, and thus IOP can be reduced. Based on recent results of a number of clinical trials, lens extraction alone or in combination with other IOP-lowering surgeries, may therefore play a more important role in the treating primary angle closure glaucoma. In cases when greater IOP-lowering effect is needed or if drug dependency has to be minimized, combined procedures, such as phacotrabeculectomy, can be considered, but the surgical risk can be higher than lens extraction alone. PMID:27014390

  15. Advanced composites technology program

    NASA Technical Reports Server (NTRS)

    Davis, John G., Jr.

    1993-01-01

    This paper provides a brief overview of the NASA Advanced Composites Technology (ACT) Program. Critical technology issues that must be addressed and solved to develop composite primary structures for transport aircraft are delineated. The program schedule and milestones are included. Work completed in the first 3 years of the program indicates the potential for achieving composite structures that weigh less and are cost effective relative to conventional aluminum structure. Selected technical accomplishments are noted. Readers who are seeking more in-depth technical information should study the other papers included in these proceedings.

  16. 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

  17. 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. PMID:23974980

  18. Effects of primary selective laser trabeculoplasty on anterior segment parameters

    PubMed Central

    Guven Yilmaz, Suzan; Palamar, Melis; Yusifov, Emil; Ates, Halil; Egrilmez, Sait; Yagci, Ayse

    2015-01-01

    AIM To investigate the effects of selective laser trabeculoplasty (SLT) on the main numerical parameters of anterior segment with Pentacam rotating Scheimpflug camera in patients with ocular hypertension (OHT) and primary open angle glaucoma (POAG). METHODS Pentacam measurements of 45 eyes of 25 (15 females and 10 males) patients (12 with OHT, 13 with POAG) before and after SLT were obtained. Measurements were taken before and 1 and 3mo after SLT. Pentacam parameters were compared between OHT and POAG patients, and age groups (60y and older, and younger than 60y). RESULTS The mean age of the patients was 57.8±13.9 (range 20-77y). Twelve patients (48%) were younger than 60y, while 13 patients (52%) were 60y and older. Measurements of pre-SLT and post-SLT 1mo were significantly different for the parameters of central corneal thickness (CCT) and anterior chamber volume (ACV) (P<0.05). These parameters returned back to pre-SLT values at post-SLT 3mo. Decrease of ACV at post-SLT 1mo was significantly higher in younger than 60y group than 60y and older group. There was no statistically significant difference in Pentacam parameters between OHT and POAG patients at pre- and post-treatment measurements (P>0.05). CONCLUSION SLT leads to significant increase in CCT and decrease in ACV at the 1st month of the procedure. Effects of SLT on these anterior segment parameters, especially for CCT that interferes IOP measurement, should be considered to ensure accurate clinical interpretation. PMID:26558208

  19. 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…

  20. 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…

  1. 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.

  2. 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.

  3. 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.

  4. SERI advanced wind turbine blades

    NASA Astrophysics Data System (ADS)

    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 percent to 30 percent more energy than conventional blades.

  5. 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).

  6. Advanced computing

    NASA Technical Reports Server (NTRS)

    1991-01-01

    Advanced concepts in hardware, software and algorithms are being pursued for application in next generation space computers and for ground based analysis of space data. The research program focuses on massively parallel computation and neural networks, as well as optical processing and optical networking which are discussed under photonics. Also included are theoretical programs in neural and nonlinear science, and device development for magnetic and ferroelectric memories.

  7. Advanced Nanoemulsions

    NASA Astrophysics Data System (ADS)

    Fryd, Michael M.; Mason, Thomas G.

    2012-05-01

    Recent advances in the growing field of nanoemulsions are opening up new applications in many areas such as pharmaceuticals, foods, and cosmetics. Moreover, highly controlled nanoemulsions can also serve as excellent model systems for investigating basic scientific questions about soft matter. Here, we highlight some of the most recent developments in nanoemulsions, focusing on methods of formation, surface modification, material properties, and characterization. These developments provide insight into the substantial advantages that nanoemulsions can offer over their microscale emulsion counterparts.

  8. Complications and Outcomes of Primary Phacotrabeculectomy with Mitomycin C in a Multi-Ethnic Asian Population

    PubMed Central

    Sng, Chelvin; Aquino, Maria C.; Chew, Paul

    2015-01-01

    Purpose To determine the occurrence of intraoperative and postoperative complications up to three years after primary phacotrabeculectomy with intraoperative use of Mitomycin C (MMC) in primary open angle (POAG) and primary angle closure glaucoma (PACG) patients, and the effect of postoperative complications on surgical outcome. Methods Retrospective review of 160 consecutive patients with POAG (n = 105) and PACG (n = 55), who underwent primary phacotrabeculectomy with MMC at the National University Hospital, Singapore, from January 1, 2008 to December 31, 2010. Data was collected using a standardized form that included patient demographic information, ocular characteristics and postoperative complications, including hypotony (defined as intraocular pressure < 6 mmHg), shallow anterior chamber (AC) and hyphema. Results The mean age ± standard deviation (SD) of patients was 68.2 ± 8.2 years. No patient lost light perception during duration of follow-up. 77% of the postoperative complications occurred within the first month only. The commonest complications were hypotony (n = 41, 25.6%), hyphema (n = 16, 10.0%) and shallow AC (n = 16, 10.0%). Five patients (3.1%) required reoperation for their complications. Early hypotony (defined as hypotony < 30 days postoperatively) was an independent risk factor for surgical failure (hazard ratio [HR], 5.1; 95% CI, 1.6–16.2; p = 0.01). Hypotony with another complication was also a risk factor for surgical failure (p < 0.02). Conclusions Hypotony, hyphema and shallow AC were the commonest postoperative complications in POAG and PACG patients after phacotrabeculectomy with MMC. Most complications were transient and self-limiting. Early hypotony within the first month was a significant risk factor for surgical failure. PMID:25775362

  9. Primary biliary cirrhosis

    MedlinePlus

    Primary biliary cirrhosis is irritation and swelling (inflammation) of the bile ducts of the liver. This blocks the flow ... ducts in the liver is not known. However, primary biliary cirrhosis is an autoimmune disorder. That means your body's ...

  10. 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, ...

  11. 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.

  12. 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…

  13. 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…

  14. 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.

  15. Primary Hyperparathyroidism: An Overview

    PubMed Central

    MacKenzie-Feder, Jessica; Sirrs, Sandra; Anderson, Donald; Sharif, Jibran; Khan, Aneal

    2011-01-01

    Primary hyperparathyroidism is a common condition that affects 0.3% of the general population. Primary and tertiary care specialists can encounter patients with primary hyperparathyroidism, and prompt recognition and treatment can greatly reduce morbidity and mortality from this disease. In this paper we will review the basic physiology of calcium homeostasis and then consider genetic associations as well as common etiologies and presentations of primary hyperparathyroidism. We will consider emerging trends in detection and measurement of parathyroid hormone as well as available imaging modalities for the parathyroid glands. Surgical indications and approach will be reviewed as well as medical management of primary hyperparathyroidism with bisphosphonates and calcimimetics. PMID:21747852

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. Creating advanced health informatics certification.

    PubMed

    Gadd, Cynthia S; Williamson, Jeffrey J; Steen, Elaine B; Fridsma, Douglas B

    2016-07-01

    In 2005, AMIA leaders and members concluded that certification of advanced health informatics professionals would offer value to individual practitioners, organizations that hire them, and society at large. AMIA's work to create advanced informatics certification began by leading a successful effort to create the clinical informatics subspecialty for American Board of Medical Specialties board-certified physicians. Since 2012, AMIA has been working to establish advanced health informatics certification (AHIC) for all health informatics practitioners regardless of their primary discipline. In November 2015, AMIA completed the first of 3 key tasks required to establish AHIC, with the AMIA Board of Directors' endorsement of proposed eligibility requirements. This AMIA Board white paper describes efforts to establish AHIC, reports on the current status of AHIC components, and provides a context for the proposed AHIC eligibility requirements. PMID:27358327

  2. 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.

  3. Advanced capacitors

    NASA Astrophysics Data System (ADS)

    Parker, R. D.; Buritz, R. S.; Taylor, A. R.; Bullwinkel, E. P.

    1982-11-01

    An experimental development program was conducted to develop and test advanced dielectric materials for capacitors for airborne power systems. High rep rate and low rate capacitors for use in pulse-forming networks, high voltage filter capacitors, and high frequency ac capacitors for series resonant inverters were considered. The initial goal was to develop an improved polysulfone film. Initially, low breakdown strength was thought to be related to inclusions of conductive particles. The effect of filtration of the casting solution was investigated. These experiments showed that more filtration was not the entire solution to low breakdown. The film samples were found to contain dissolved ionic impurities that move through the dielectric when voltage is applied and cause enhancement of the electric field. These contaminants enter the film via the resin and solvent, and can be partially removed. However, these treatments did not significantly improve the breakdown characteristics. A new material, Ultem, was proposed for use in high energy density capacitors. This new polyetherimide resin has properties similar to polysulfone and polyimide, with improvement in breakdown characteristics and temperature capability. The technique of casting films on a roughened drum was demonstrated, and found useful in preparing textured films. this is the first step toward a replacement for kraft paper.

  4. Advanced capacitors

    NASA Astrophysics Data System (ADS)

    Ennis, J. B.; Buritz, R. S.

    1984-10-01

    This report describes an experimental program to develop and test advanced dielectric materials for capacitors for airborne power systems. Five classes of capacitors were considered: high rep rate and low rep rate pulse capacitors for use in pulse-forming networks, high voltage filter capacitors, high frequency AC capacitors for series resonant inverters, and AC filter capacitors. To meet these requirements, existing dielectric materials were modified, and new materials were developed. The initial goal was to develop an improved polysulfone film with fewer imperfections that could operate at significantly higher electrical stresses. It was shown that contaminants enter the film via the resin and solvent, and that they can be partially removed. As far as developed, however, these treatments did not significantly improved the breakdown characteristics. The technique of casting films on a roughened drum was demonstrated, and found useful in preparing textured films -- the first step toward a replacement for Kraft paper. A new material, Ultem, was proposed for use in high energy density capacitors. This new polyetherimide resin has properties similar to polysulfone and polyimide, with improvement in breakdown characteristics and temperature capability. This material was selected for further study in model capacitor designs.

  5. Future advances.

    PubMed

    Celesia, Gastone G; Hickok, Gregory

    2015-01-01

    Future advances in the auditory systems are difficult to predict, and only educated guesses are possible. It is expected that innovative technologies in the field of neuroscience will be applied to the auditory system. Optogenetics, Brainbow, and CLARITY will improve our knowledge of the working of neural auditory networks and the relationship between sound and language, providing a dynamic picture of the brain in action. CLARITY makes brain tissue transparent and offers a three-dimensional view of neural networks, which, combined with genetically labeling neurons with multiple, distinct colors (Optogenetics), will provide detailed information of the complex brain system. Molecular functional magnetic resonance imaging (MRI) will allow the study of neurotransmitters detectable by MRI and their function in the auditory pathways. The Human Connectome project will study the patterns of distributed brain activity that underlie virtually all aspects of cognition and behavior and determine if abnormalities in the distributed patterns of activity may result in hearing and behavior disorders. Similarly, the programs of Big Brain and ENIGMA will improve our understanding of auditory disorders. New stem-cell therapy and gene therapies therapy may bring about a partial restoration of hearing for impaired patients by inducing regeneration of cochlear hair cells. PMID:25726297

  6. Advanced Crew Escape Suit.

    PubMed

    1995-09-01

    Design of the S1032 Launch Entry Suit (LES) began following the Challenger loss and NASA's decision to incorporate a Shuttle crew escape system. The LES (see Figure 1) has successfully supported Shuttle missions since NASA's Return to Flight with STS-26 in September 1988. In 1990, engineers began developing the S1035 Advanced Crew Escape Suit (ACES) to serve as a replacement for the LES. The ACES was designed to be a simplified, lightweight, low-bulk pressure suit which aided self donning/doffing, provided improved comfort, and enhanced overall performance to reduce crew member stress and fatigue. Favorable crew member evaluations of a prototype led to full-scale development and qualification of the S1035 ACES between 1990 and 1992. Production of the S1035 ACES began in February 1993, with the first unit delivered to NASA in May 1994. The S1035 ACES first flew aboard STS-68 in August 1994 and will become the primary crew escape suit when the S1032 LES ends its service life in late 1995. The primary goal of the S1035 development program was to provide improved performance over that of the S1032 to minimize the stress and fatigue typically experienced by crew members. To achieve this, five fundamental design objectives were established, resulting in various material/configuration changes. PMID:11540717

  7. Metastases of unknown primary site.

    PubMed

    Lembersky, B C; Thomas, L C

    1996-01-01

    Despite the fact that effective therapy does not currently exist for the majority of patients presenting with metastases of unknown primary site, the last decade has witnessed significant advances in the approach to this heterogeneous disease. The use of modern pathologic techniques that frequently provide better diagnostic precision and the recognition of specific subgroups with a favorable prognosis and responsiveness to treatment has improved the outcome for some patients. Currently the diagnostic strategy should emphasize the rapid identification of patients likely to benefit from available therapy, whereas clinical research should focus on the development of more effective treatments for those patients with unresponsive tumors. In the future, continued improvements in the molecular characterization of these tumors will likely enhance understanding of the metastatic process, allow for more specific definitions of cell lineage, and provide insights for better therapy. PMID:8569295

  8. Primary pulmonary leiomyoma

    PubMed Central

    Wu, Peng; Venkatachalam, Jonathen; Lee, Victor Kwan Min

    2016-01-01

    Abstract Leiomyoma is a smooth muscle neoplasm that commonly occurs in the genitourinary system and the gastrointestinal tract of the body. Primary pulmonary leiomyoma is rarely reported in literature. We report a rare case of primary pulmonary leiomyoma of a 55‐year‐old male patient presenting with symptoms of cough for six months. PMID:27516882

  9. Primary Science Focus

    ERIC Educational Resources Information Center

    Turner, Jane

    2011-01-01

    Liz Lawrence has recently finished her term as Chair of Primary Science Committee (PSC). She is one of the 41 hub leaders who have led and mentored 192 schools across England and British Forces' schools in Germany, to achieve the first ever nationally recognised awards to celebrate excellence in primary science. In this article, the author writes…

  10. Multiple primary bronchogenic carcinomas.

    PubMed

    Yang, X; Ji, H; Paljarvi, L; Soimakallio, S

    1996-07-01

    Multiple primary bronchogenic carcinomas (MPBCa) are extremely rare. The differentiation of a MPBCa from a pulmonary metastasis due to an extrathoracic neoplasm is sometimes difficult. We reviewed 324 pathologically proved primary pulmonary carcinomas and found six cases of MPBCa (1.9%). We herewith present the series and discuss the diagnosis of MPBCa. PMID:21594435

  11. 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…

  12. 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 medicine. It…

  13. 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)

  14. Primary Health Care.

    ERIC Educational Resources Information Center

    Lauffer, Sandra, Ed.

    1979-01-01

    This report contains 13 articles and book/film reviews on various topics related to the diffusion of health care information in developing countries; beginning with two articles which define primary health care, and suggest principles related to the community, communication, and the health practitioner upon which primary health care should be…

  15. Primary pulmonary leiomyoma.

    PubMed

    Wu, Peng; Venkatachalam, Jonathen; Lee, Victor Kwan Min; Tan, Sze Khen

    2016-05-01

    Leiomyoma is a smooth muscle neoplasm that commonly occurs in the genitourinary system and the gastrointestinal tract of the body. Primary pulmonary leiomyoma is rarely reported in literature. We report a rare case of primary pulmonary leiomyoma of a 55-year-old male patient presenting with symptoms of cough for six months. PMID:27516882

  16. [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. PMID:24770539

  17. Developing primary health care.

    PubMed Central

    Jarman, B; Cumberlege, J

    1987-01-01

    Primary health care is best provided by a primary health care team of general practitioners, community nurses, and other staff working together from good premises and looking after the population registered with the practice. It encourages personal and continuing care of patients and good communication among the members of the team. Efforts should be made to foster this model of primary care where possible and also to evaluate its effectiveness. Community services that are not provided by primary care teams should be organised on a defined geographical basis, and the boundaries of these services should coincide as much as possible. Such arrangements would facilitate effective community care and health promotion and can be organised to work well with primary care teams. The patient's right to freedom of choice of a doctor, however, should be retained, as it adds flexibility to the rigidity of fixed geographically based services. PMID:3119003

  18. Advance care planning in the elderly.

    PubMed

    Lum, Hillary D; Sudore, Rebecca L; Bekelman, David B

    2015-03-01

    Key components of advance care planning (ACP) for the elderly include choosing a surrogate decision maker, identifying personal values, communicating with surrogates and clinicians, documenting wishes in advance directives, and translating values and preferences for future medical care into medical orders. ACP often involves multiple brief discussions over time. This article outlines common benefits and barriers to ACP in primary care, and provides practical approaches to integrating key ACP components into primary care for older adults. Opportunities for multidisciplinary teams to incorporate ACP into brief clinic visits are highlighted. PMID:25700590

  19. 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.

  20. Efficacy of Adjunctive Subconjunctival Bevacizumab on the Outcomes of Primary Trabeculectomy With Mitomycin C: A Prospective Randomized Placebo-controlled Trial

    PubMed Central

    Orapiriyakul, Lachaya; Kittigoonpaisan, Kaneungnit; Tantisarasart, Thawat; Wangsupadilok, Boonchai

    2015-01-01

    Purpose: To evaluate the efficacy of subconjunctival bevacizumab (ScB) as adjuvant therapy to primary trabeculectomy with mitomycin C (MMC) in primary open-angle glaucoma. Materials and Methods: Forty-six eyes of primary open-angle glaucoma patients were randomized to receive ScB (1.25 mg/0.05 mL) injections (the MMC+ScB group) at the end of the operations, or sham-treated controls (the MMC group). Intraocular pressure (IOP) was the primary outcome and secondary outcomes included bleb appearance, visual acuity, number of medications, complications, and proportion of eyes achieving successful outcomes at the 12-month follow-up. Results: Of 39 eyes, 20 eyes from the MMC+ScB group, and 19 eyes from the MMC group completed the follow-up. The mean postoperative IOP was 15.5±4.1 mm Hg in the MMC+ScB group (P<0.01; 40% reduction), and 14.7±4.3 mm Hg in the MMC group (P<0.01; 44% reduction). The differences in IOPs, at all follow-up visits, were not significant (P>0.05). The mean bleb vascularity score, at 1 month, in the MMC+ScB group was lower than the MMC group (1.55±0.51 vs. 2.26±0.6, respectively, P=0.01), but was not retained at follow-ups. The success rates at 12 months after surgery were 85% in the MMC+ScB group and 89.5% in the MMC group (P=0.53). The cumulative probabilities of surgical success were 80% and 73.7% in the MMC+ScB and in the MMC group, respectively (P=0.52). Conclusion: Single adjunctive ScB injection did not appear to have an additive benefit on outcomes of MMC trabeculectomy, in terms of IOPs and success rates. PMID:25393038

  1. Progress at the Vatican Advanced Technology Telescope

    NASA Astrophysics Data System (ADS)

    West, Steve C.; Nagel, Robert H.; Harvey, David A.; Brar, A.; Phillips, B.; Ray, J.; Trebisky, T. J.; Cromwell, Richard H.; Woolf, Neville J.; Corbally, Chris; Boyle, R.; Blanco, Daniel R.; Otten, L.

    1997-03-01

    The Vatican Advanced Technology Telescope incorporates a fast (f/1.0) borosilicate honeycomb primary mirror and an f/0.9 secondary in an aplanatic Gregorian optical configuration. We provide a brief technical and performance overview by describing the optical layout, the primary and secondary mirror systems, and the telescope drive and control system. Results from a high resolution wavefront sensor and a current wide-field image taken at the f/9 focus demonstrates the overall fine performance of the telescope.

  2. Primary Peritoneal Cancer

    MedlinePlus

    ... Gynecologic Cancer Foundation wins The 2001 Associations Advance America “Award of Excellence” Press Release: Gynecologic Cancer Foundation Named One of “America’s Best 100 Charities” Press Release: Gynecologic Cancer Foundation ...

  3. 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.

  4. 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...

  5. Genetics of primary hyperaldosteronism.

    PubMed

    Dutta, Ravi Kumar; Söderkvist, Peter; Gimm, Oliver

    2016-10-01

    Hypertension is a common medical condition and affects approximately 20% of the population in developed countries. Primary aldosteronism is the most common form of secondary hypertension and affects 8-13% of patients with hypertension. The two most common causes of primary aldosteronism are aldosterone-producing adenoma and bilateral adrenal hyperplasia. Familial hyperaldosteronism types I, II and III are the known genetic syndromes, in which both adrenal glands produce excessive amounts of aldosterone. However, only a minority of patients with primary aldosteronism have one of these syndromes. Several novel susceptibility genes have been found to be mutated in aldosterone-producing adenomas: KCNJ5, ATP1A1, ATP2B3, CTNNB1, CACNA1D, CACNA1H and ARMC5 This review describes the genes currently known to be responsible for primary aldosteronism, discusses the origin of aldosterone-producing adenomas and considers the future clinical implications based on these novel insights. PMID:27485459

  6. 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)

  7. [Results of primary healthcare].

    PubMed

    Duponchel, J L

    2004-01-01

    The concept of primary healthcare was formulated at the international conference held in Alma-Ata (USSR) on September 6 to 12, 1978. Over the past quarter-century, the term "primary healthcare" has been widely used as a basis for implementing healthcare policies in various nations, especially those considered as developing countries. However many programs initiated in the name of the primary healthcare concept have only partially complied with the spirit of the final declaration of Alma-Ata. Analysis of the healthcare in Mali shows that the system followed that evolution. Although considerable time and energy were regrettably wasted in implementing the village health agent strategy, this phase may have been a necessary step in the political development of the state at that time. Recent changes in the country's healthcare system in compliance with the original principles of primary healthcare show that the 1978 declaration is sound and remains pertinent as democracy makes further gains in the world. PMID:15816127

  8. Staging Primary CNS Lymphoma

    MedlinePlus

    ... large vein near the heart. Having a weakened immune system may increase the risk of developing primary CNS ... immunodeficiency syndrome (AIDS) or other disorders of the immune system or who have had a kidney transplant . For ...

  9. 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)

  10. Primary Lateral Sclerosis

    MedlinePlus

    ... synthesizers, and wheelchairs ma help some people retain independence.. Speech therapy may be useful for those with ... prevent, and ultimately cure these devastating diseases. NIH Patient Recruitment for Primary Lateral Sclerosis Clinical Trials At ...

  11. 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 ...

  12. Treatment of primary syphilis.

    PubMed

    Elliott, W C

    1976-12-01

    Reports in the English language of the treatment of primary syphilis are reviewed. Except for benzathine penicillin, the efficacy of the currently recommended dosage schedules are documented only by Schroeter et al. Although these investigators reported generally acceptable failure rates, further study is necessary to determine: (1) if differences in efficacy exist among regimes; (2) if the current schedules are equally effective in both primary and secondary syphilis; and (3) if increased dosages reduce failure rates. PMID:1010777

  13. 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

  14. 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

  15. Advanced irrigation engineering: Precision and Precise

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Irrigation advances in precision irrigation (PI) or site-specific irrigation (SSI) have been considerable in research; however commercialization lags. A primary necessity for it is variability in soil texture that affects soil water holding capacity and crop yield. Basically, SSI/PI uses variable ra...

  16. Advanced irrigation engineering: Precision and Precise

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Irrigation advances in precision irrigation (PI) or site specific irrigation (SSI) have been considerable in research; however commercialization lags. A primary necessity for PI/SSI is variability in soil texture that affects soil water holding capacity and crop yield. Basically, SSI/PI uses variabl...

  17. Recent advances in paediatric respiratory medicine.

    PubMed

    Turnbull, Andrew; Balfour-Lynn, Ian M

    2016-02-01

    This review highlights important advances in paediatric respiratory medicine since 2014, excluding cystic fibrosis. It focuses mainly on the more common conditions, bronchopulmonary dysplasia, bronchiolitis and preschool wheezing, asthma, pneumonia and sleep, and highlights some of the rarer conditions such as primary ciliary dyskinesia and interstitial lung disease (ILD). PMID:26289061

  18. 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.

  19. 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

  20. Modification of Shock Train Induced Turbulence by a Variable Nozzle Opening Angle and Circumferential Suction

    NASA Astrophysics Data System (ADS)

    Grzona, A.; Weiss, Alexander; Olivier, Herbert

    In a continuous cold gas wind tunnel, with a convergent-divergent nozzle geometry similar to a pilot facility for the gas-phase synthesis of nanoparticles [3] the recompression from supersonic to subsonic flow conditions is conducted by a shock train. A principle sketch of a typical shock train is depicted in Fig. 1 while a detailed description of the shock train phenomenon and a comprehensive review of its timeaveraged behaviour can be found in [6].

  1. Discovery of the ROCK inhibitor netarsudil for the treatment of open-angle glaucoma.

    PubMed

    Sturdivant, Jill M; Royalty, Susan M; Lin, Cheng-Wen; Moore, Lori A; Yingling, Jeffrey D; Laethem, Carmen L; Sherman, Bryan; Heintzelman, Geoffrey R; Kopczynski, Casey C; deLong, Mitchell A

    2016-05-15

    Inhibition of Rho kinase (ROCK) to improve fluid outflow through the trabecular meshwork and lower intraocular pressure is a strategy for the development of new anti-glaucoma agents. Alpha-aryl-beta-amino isoquinoline analogs were identified as potent ROCK inhibitors. Compounds that provided a longer duration of intraocular pressure reduction in Dutch Belted rabbits also inhibited norepinephrine transporter. Ester 60 improved bioavailability of its parent ROCK inhibitor, 29 (Ki=0.2nM) and demonstrated an effective and sustained IOP reduction for 24h after dosing. From these studies, netarsudil (a.k.a. AR-13324) was discovered and is currently in clinical trials for the treatment of glaucoma and ocular hypertension. PMID:27072905

  2. Variable opening angle of emission cone of Jovian decameter radiation generated by cyclotron maser instability

    NASA Astrophysics Data System (ADS)

    Galopeau, P. H. M.; Boudjada, M. Y.; Rucker, H. O.

    2015-10-01

    A recent study of the Io-controlled Jovian decameter radiation revealed that the radio emission is beamed in a hollow cone which presents a flattening in a specific direction linked to the local magnetic field in the source. We investigate some reasons for the existence of such a flattening. The Jovian decameter radiation, like the other auroral radio emissions emanating from the magnetized planets in the solar system, is known to be produced by the cyclotron maser instability (CMI). This mechanism allows the direct amplification of the waves through a resonant coupling between the electron population of the plasma and the electromagnetic.

  3. Gas fired Advanced Turbine System

    SciTech Connect

    LeCren, R.T.; White, D.J.

    1993-01-01

    The primary objective of the first phase of the Advanced Gas Turbine System (ATS) program was the concept definition of an advanced engine system that meets efficiency and emission goals far exceeding those that can be provided with today`s equipment. The thermal efficiency goal for such an advanced industrial engine was set at 50% some 15 percentage points higher than current equipment levels. Exhaust emissions goals for oxides of nitrogen (NO{sub x}), carbon monoxide (CO), and unburned hydrocarbons (UH) were fixed at 8 parts per million by volume (ppmv), 20 ppmv, and 20 ppmv respectively, corrected to 15% oxygen (O{sub 2}) levels. Other goals had to be addressed; these involved reducing the cost of power produced by 10 percent and improving or maintaining the reliability, availability, and maintainability (RAM) at current levels. This advanced gas turbine was to be fueled with natural gas, and it had to embody features that would allow it bum coal or coal derived fuels.

  4. 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.

  5. 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

  6. 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

  7. 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.

  8. Advances in corneal cell therapy.

    PubMed

    Fuest, Matthias; Yam, Gary Hin-Fai; Peh, Gary Swee-Lim; Mehta, Jodhbir S

    2016-09-01

    Corneal integrity is essential for visual function. Transplantation remains the most common treatment option for advanced corneal diseases. A global donor material shortage requires a search for alternative treatments. Different stem cell populations have been induced to express corneal cell characteristics in vitro and in animal models. Yet before their application to humans, scientific and ethical issues need to be solved. The in vitro propagation and implantation of primary corneal cells has been rapidly evolving with clinical practices of limbal epithelium transplantation and a clinical trial for endothelial cells in progress, implying cultivated ocular cells as a promising option for the future. This review reports on the latest developments in primary ocular cell and stem cell research for corneal therapy. PMID:27498943

  9. 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.

  10. 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.

  11. 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.

  12. [Atorvastatin in primary prevention].

    PubMed

    Kültürsay, Hakan

    2009-03-01

    Statins are one of the most widely used drugs in medical treatment and have been shown to prevent cardiovascular disease or reduce risk in a large number of studies. Although there is a general class effect, there are differences with regard to structure and efficacy between these agents. Among these agents, atorvastatin is a potent statin whose efficacy has been demonstrated in many clinical trials. Despite the presence of numerous clinical studies, data on atorvastatin related to primary prevention are limited compared to secondary prevention. In this article, clinical results of primary prevention trials with atorvastatin and data on its cost-effectiveness are reviewed. It is concluded that atorvastatin has a role in primary prevention and the cost of its use seems to be lower than commonly accepted cost-effectiveness thresholds. PMID:19404046

  13. Endocrine and Hypertensive Disorders of Potassium Regulation: Primary Aldosteronism

    PubMed Central

    Weiner, I. David

    2013-01-01

    The identification that primary aldosteronism is a common cause of resistant hypertension is a significant advance in our ability to care for patients with hypertension. Primary aldosteronism is common, and when unrecognized is associated with increased incidence of adverse cardiovascular outcomes. Identification of primary aldosteronism is based upon use of the plasma aldosterone level, plasma renin activity and the aldosterone:renin ratio (ARR). Differentiation between unilateral and bilateral autonomous adrenal aldosterone production then guides further therapy, with use of mineralocorticoid receptor blockers for those with bilateral autonomous adrenal aldosterone production and laparoscopic adrenalectomy for those with unilateral autonomous aldosterone production. In this review, we discuss in detail the pathogenesis of primary aldosteronism-induced hypertension and potassium disorders, the evaluation of the patient with suspected primary aldosteronism and the management of primary aldosteronism, both through medications and through surgery. PMID:23953804

  14. 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. Patients who have a weakened immune system are at high risk of primary lymphoma of the ...

  15. 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. ...

  16. Psychiatry and primary care.

    PubMed

    Goldberg, David

    2003-10-01

    There is now almost universal recognition that primary care is the place where most mentally distressed people first present for help. However, the pace at which the health system has adapted to this reality varies greatly from country to country, depending on the amount of resource devoted to mental illness services, the way in which primary care physicians have organized their practice, and the inertia of the system. Here we present several models from developed and developing countries and address briefly the issue of training of health workers. PMID:16946921

  17. Primary Intracranial Leptomeningeal Melanomatosis

    PubMed Central

    Kim, Do-Hyoung; Lee, Chae-Heuck; Joo, Mee

    2015-01-01

    Primary intracranial malignant melanoma is a very rare and highly aggressive tumor with poor prognosis. A 66-year-old female patient presented a headache that had been slowly progressing for several months. A large benign pigmented skin lesion was found on her back. A brain MRI showed multiple linear signal changes with branching pattern and strong enhancement in the temporal lobe. The cytological and immunohiostochemical cerebrospinal fluid examination confirmed malignant melanoma. A biopsy confirmed that the pigmented skin lesion on the back and the conjunctiva were benign nevi. We report a case of primary intracranial malignant melanoma and review relevant literatures. PMID:26819692

  18. Sleep and primary headaches.

    PubMed

    Aguggia, Marco; Cavallini, M; Divito, N; Ferrero, M; Lentini, A; Montano, V; Tinebra, M C; Saracco, M G; Valfrè, W

    2011-05-01

    The relationship between sleep and primary headaches has been known for over a century, particularly for headaches occurring during the night or early morning. Migraine, tension-tyre headache, and cluster headache may cause sleep fragmentation, insomnia, and hypersomnia, causing considerable social and economical costs and several familial problems. By contrast, sleep disorders may themselves trigger headache attacks. Finally, headaches and sleep disorders can also be symptoms of other underlying pathologies. Despite this background, there is still no clarity about the mechanism that links these two entities and their interdependence remains to be defined. Patients with primary headache should undergo a careful assessment of sleep habits. PMID:21533713

  19. Primary cutaneous nocardiosis.

    PubMed

    Jiang, Shan; Jiang, Guan; Lei, Tie-Chi

    2014-11-01

    Nocardiosis is a rare human infection due to ubiquitous soil born gram-positive, filametous aerobic bacteria. First signs are frequently cutaneous either as part of systemic infection disseminated to the skin, or as primary cutaneous inoculation. An 88 years old man presented with a 3-day history of red papules and pustules with pain on his forehead. The combination of the unusual clinical presentation, laboratory examinations, and a favorable response to co-trimoxazole therapy were consistent with a diagnosis of primary cuteneous nocardiosis. Early recognition and treatment of the disease will improve the cure rate. PMID:25518763

  20. 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.

  1. Recent advances of nanodosimetry.

    PubMed

    Grosswendt, B

    2004-01-01

    The early damage to genes and cells due to ionizing radiation is initiated by the overlay of the track structure of charged particles and of the structure of radiosensitive sub-cellular volumes. As a result of this overlay, a specified number of ionizations (the ionization cluster size) is formed per primary particle. Therefore, one of the aims of nanodosimetry is to determine ionization cluster-size distributions in nanometric volumes of liquid water, as a substitute to sub-cellular structures. After a short description of the main aspects of cluster-size formation by charged particles, an overview of the advanced measuring techniques that use millimetric target volumes filled with a low-pressure gas to simulate nanometric target volumes at unit density is given. Afterwards, physical principles are discussed which are applicable to convert ionization cluster-size distributions measured in gases into those for liquid water. Finally, a tentative possibility is proposed of how to relate parameters derived from cluster-size distributions in liquid water to parameters derived from radiation-induced radiobiological experiments. PMID:15353748

  2. 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. PMID:26320047

  3. 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…

  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. 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.

  6. 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

  7. Primary Keyboarding Curriculum.

    ERIC Educational Resources Information Center

    Peterson, Valery; And Others

    Beginning with a rationale for implementing a primary grade keyboarding course, this paper describes the implementation of such a course at the Bernardsville (New Jersey) Elementary School. The methods and procedures discussed include the essential concepts to consider when teaching keyboarding and the materials necessary to implement the program.…

  8. Primary Pulmonary Hodgkin Lymphoma

    PubMed Central

    Tanveer, Shumaila; El Damati, Ahmed; El Baz, Ayman; Alsayyah, Ahmed; ElSharkawy, Tarek

    2015-01-01

    Primary pulmonary Hodgkin lymphoma (PPHL) is a rare disease. Herein, we report a case of PPHL with diagnostic concerns encountered during initial evaluation which is of paramount importance to keep the differential diagnosis in cases with high index of suspicion for this rare entity. PMID:26788271

  9. Primary: A Simulation Game.

    ERIC Educational Resources Information Center

    Shelly, Ann

    A game designed to introduce elementary and middle school students to the primary election process and its operational elements through simulation and role playing activities is presented in this document. A hypothetical town of Notae which has been controlled by one political party for years without resulting change is described. Issues in the…

  10. Primary Guidance Activities.

    ERIC Educational Resources Information Center

    Hauck, Ruth, Comp.

    Designed for the primary grades, the guidance activities in this document cover thirty-three topical areas: capabilities, changes, cooperation, criticism, differences, family, feelings, free time, friends, following directions, handicaps, honesty, improving environment, kindness, patience, paying attention, problem solving, rejection,…

  11. Primary Neonatal Diaphragmatic Abscess

    PubMed Central

    Zouari, Mohamed; Jallouli, Mohamed; Ben Thabet, Afef; Ben Dhaou, Mahdi; Gargouri, Abdellatif; Mhiri, Riadh

    2015-01-01

    Neonatal diaphragmatic abscesses are extremely rare and they usually develop by direct extension from a liver abscess. The first case of primary diaphragmatic abscess in a neonate is reported and the difficulties of diagnosing this rare entity are discussed. PMID:26023529

  12. Primary hepatic angiosarcoma.

    PubMed

    Chaudhary, P; Bhadana, U; Singh, R A K; Ahuja, A

    2015-09-01

    Primary hepatic angiosarcoma is a rare, aggressive tumor; composed of spindle or pleomorphic cells that line, or grow into, the lumina of pre-existing vascular spaces like sinusoids and terminal hepatic venules; with only about 200 cases diagnosed annually worldwide but it is the most common primary malignant mesenchymal tumor of the liver in adults and accounts for 2% of all primary hepatic malignancies. HAS occurs in association with known chemical carcinogens, but 75% of the tumors have no known etiology. Patients present with vague symptoms like abdominal pain, weight loss, fatigue or an abdominal mass. Hepatic angiosarcoma is usually multicentric and involves both lobes, entire liver may also found to be involved. CD31 is the most reliable marker. These tumors lack specific features on imaging, so, pathological diagnosis is necessary. There are no established treatment guidelines because of low frequency and aggressive nature of tumor, chemotherapy is only palliative, liver resection is indicated for solitary mass and liver transplant is contraindicated. The aim of this article is to comprehensively review all the available literature and to present detailed information and an update on primary hepatic angiosarcoma. PMID:26008857

  13. Writing for Primary Science

    ERIC Educational Resources Information Center

    Mawby, Tara, Ed.

    2011-01-01

    In this article, two short pieces are presented to show educators just what a good article and a good review could have in them. This article has been written for the purpose of illustrating a good example, but is also representative of the type of content the editors encourage in "Primary Science": practical and active, with images. They also…

  14. 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. PMID:26985402

  15. Primary Lymphoma of Bone

    PubMed Central

    Choi, Jun Yong; Hahn, Jee Sook; Suh, Chang Ok; Yang, Woo Ick

    2002-01-01

    Background: Primary lymphoma of bone is a rare disease. There is yet no systematical evaluation of primary lymphoma of bone in Korea. Here we report our experience of sixteen cases with primary lymphoma of bone focusing on the survival. Methods: Sixteen cases, collected for 13 years, were evaluated on the clinical presentation, histologic subtype, stage and treatment outcomes of the primary bone lymphoma. Results: The most common presenting complaint was bone pain. Malignant lymphoma of bone involved a wide variety of sites, the most prevalent site of which in this study was the spine. Most of the cases were in the diffuse large B-cell category. The clinical stage of lymphoma was IEA in two cases, IIEA in three cases, IVEA in five cases and IVEB in three cases. All treated cases received systemic chemotherapy and ten cases among them were treated with combined modality therapy. Median overall survival was not reached after median follow-up period of 28 months and five-year overall survival rate was 54%. Conclusion: More promising therapeutic strategies are needed for survival improvement on more accumulated cases. PMID:12298430

  16. Primary Biliary Cirrhosis

    MedlinePlus

    ... liver cancer every 6 to 12 months. Health care providers use blood tests, ultrasound, or both to check for signs of ... the diagnosis of primary biliary cirrhosis. A health care provider uses the test selectively when he or she is concerned that ...

  17. Primary publication in microprint

    USGS Publications Warehouse

    Herman, C.M.; Davis, D.E.

    1964-01-01

    This is a progress report on an experiment to demonstrate practicality of such publication. Based on a study conducted since 1959 through the publication of 'Wildlife Disease', the co-authors review the original aims, accomplishments, and future of primary publication in microprint. Space and cost savings, as well as author and reader reactions, portend further developments and use of this medium.

  18. 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 mentioned. The result…

  19. 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.

  20. Discover Primary Science: Developing Primary Science in Ireland

    ERIC Educational Resources Information Center

    Horner, Margaret; Palmer, Marion

    2007-01-01

    "Discover Primary Science" is a major project in primary science education in Ireland. In 2006-2007 it involves 2400 primary schools, 45 host centres, and two government departments. However, it started out as a local initiative taken by one state agency in 2002 involving four Institutes of Technology and 40 primary schools. The aim of the…

  1. [Primary pulmonary sarcomas].

    PubMed

    Jakubcová, T; Jakubec, P

    2009-01-01

    Primary pulmonary sarcomas are rare diseases unlike lung carcinomas. The occurence of these sarcomas is between 0.013-0.40% of all malignant lung tumours. There are malignant mesenchymal tumours. They are flowing from the soft tissue of lung. The pulmonary sarcomas are heterogenic group with various biological behaviour. Their morfologic structure does not digger from the sarcomas of soft tissue. The primary pulmonary sarcomas occur more often in childhood and in young people unlike lung carcinomas. Radiation and some toxic substances are noted risk factors. Some gene mutations, infectious pathoghens and contraception have a possible impact on the origin of some types of the sarcomas. The current hypothesis is, that most of the sarcomas, if not all sarcomas, stem from primitive multipotent mesenchymal cell by malignant transformation in one or more lines. The diagnostic standard is biopsy from tumour with histologic and immunohistochemistry examination of a sample. The basic diagnostic problem is exclusion of a secondary origin of sarcomatic cells in the lung, because pulmonary metastasis of extrapulmonary sarcomas are more often than the primary pulmonary involvement.The optimal treatment is a resection of the tumour.The other therapeutic modalities are radiotherapy and chemotherapy, but results of these modalities are unsatisfactory. There are various chemotherapeutic regimes, monotherapy or combination regimes. The basic cytostatics are doxorubicine, iphosphamide, dacarbazine. Problems of the chemotherapy are high toxicity and relatively low curative effect about 20%.The first studies with biological treatment of the sarcomas of soft tissue have been published recently.This types of drugs could be a part of the complex management of these primary pulmonary tumours in the future. The primary pulmonary sarcomas have mostly aggresive course and often recur. Their prognosis is usually not very good. The survival median is 48 months and 5-years survival ranges

  2. 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. PMID:12412967

  3. 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

  4. 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

  5. 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.

  6. Reliability assurance for regulation of advanced reactors

    SciTech Connect

    Fullwood, R.; Lofaro, R.; Samanta, P.

    1991-01-01

    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.

  7. 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.

  8. Immunotherapy in a rare case of primary pelvic retroperitoneal melanoma.

    PubMed

    Talag, Maria Monica; Alsharedi, Mohamed; Bou Zgheib, Nadim; Lebowicz, Yehuda

    2016-01-01

    Recent advances in novel immunotherapeutic and targeted therapeutic agents have increased treatment options in patients with advanced metastatic melanoma. However, evidence in the literature on whether or not extracutaneous melanoma will acquire an equivalent advantage from these therapies is very scarce. In general, extracutaneous melanomas are rare and aggressive melanomas, which are clinically and biologically unique, with higher incidence of metastatic disease and poor prognosis. In this case report, we present a very rare case of a 54-year-old woman with primary pelvic retroperitoneal melanoma treated with an anti-PD-1 antibody, pembrolizumab. Furthermore, we explore the role of novel immunotherapies in the treatment of advanced melanoma. PMID:27624447

  9. 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.

  10. Primary Graft Failure after Heart Transplantation

    PubMed Central

    Iyer, Arjun; Kumarasinghe, Gayathri; Hicks, Mark; Watson, Alasdair; Gao, Ling; Doyle, Aoife; Keogh, Anne; Kotlyar, Eugene; Hayward, Christopher; Dhital, Kumud; Granger, Emily; Jansz, Paul; Pye, Roger; Spratt, Phillip; Macdonald, Peter Simon

    2011-01-01

    Primary graft failure (PGF) is a devastating complication that occurs in the immediate postoperative period following heart transplantation. It manifests as severe ventricular dysfunction of the donor graft and carries significant mortality and morbidity. In the last decade, advances in pharmacological treatment and mechanical circulatory support have improved the outlook for heart transplant recipients who develop this complication. Despite these advances in treatment, PGF is still the leading cause of death in the first 30 days after transplantation. In today's climate of significant organ shortages and growing waiting lists, transplant units worldwide have increasingly utilised “marginal donors” to try and bridge the gap between “supply and demand.” One of the costs of this strategy has been an increased incidence of PGF. As the threat of PGF increases, the challenges of predicting and preventing its occurrence, as well as the identification of more effective treatment modalities, are vital areas of active research and development. PMID:21837269

  11. Personalizing Treatment: Between Primary and Secondary Prevention.

    PubMed

    Blaha, Michael J

    2016-09-15

    Current American College of Cardiology/American Heart Association guidelines for the management of patients with elevated blood cholesterol increasingly emphasize assessment of atherosclerotic cardiovascular disease (ASCVD) risk in deciding when to initiate pharmacotherapy. The decision to treat is based primarily on mathematical integration of traditional risk factors, including age, sex, race, lipid values, systolic blood pressure, hypertension therapy, diabetes mellitus, and smoking. Advanced risk testing is selectively endorsed for patients when the decision to treat is otherwise uncertain, or more broadly interpreted as those patients who are at so-called "intermediate risk" of ASCVD events using traditional risk factors alone. These new guidelines also place new emphasis on a clinician-patient risk discussion, a process of shared decision making in which patient and physician consider the potential benefits of treatment, risk of adverse events, and patient preferences before making a final decision to initiate treatment. Advanced risk testing is likely to play an increasingly important role in this process as weaknesses in exclusive reliance on traditional risk factors are recognized, new non-statin therapies become available, and guidelines are iteratively updated. Comparative efficacy studies of the various advanced risk testing options suggest that coronary artery calcium scoring is most strongly predictive of ASCVD events. Most importantly, coronary artery calcium scoring appears to identify an important subgroup of patients with advanced subclinical atherosclerosis-who are "between" primary and secondary prevention-that might benefit from the most aggressive lipid-lowering pharmacotherapy. PMID:27620358

  12. Primary Pulmonary Paraganglioma

    PubMed Central

    Huang, Xin; Liang, Qi-Lian; Jiang, Liang; Liu, Qiu-Long; Ou, Wen-Ting; Li, Da-Heng; Zhang, Hui-Jie; Yuan, Gao-Le

    2015-01-01

    Abstract Primary pulmonary paraganglioma is a rare disease. We report a case of a 37-year old female patient with space-occupying lesions in the right lower pulmonary lobe during a routine examination without any symptoms. The patient underwent video-assisted thoracoscopic surgery (VATS) resection of the right middle lobe and dissection of hilar and mediastinal lymph nodes under general anesthesia. She recovered without recrudescence. Preoperative diagnosis is difficult. Accurate diagnosis requires pathological examination, and immunohistochemical test is particularly important. Complete resection is the first treatment option for solitary primary pulmonary paraganglioma; however, VATS is a better technique. Given the high local control rates and few complications of radiotherapy, it is considered as a standard treatment. PMID:26252294

  13. Primary hyperparathyroidism and nephrolithiasis.

    PubMed

    Vestergaard, Peter

    2015-05-01

    Calcifications in the kidneys may occur in the parenchyma (nephrocalcinosis), pelvis renis (nephrolithiasis) or ureters (ureterolithiasis). Several factors may protect against stone formation or promote precipitation of stones. Most stones contain calcium, and the hypercalciuria seen in primary hyperparathyroidism is a contributing factor to stone formation in the kidneys and urinary tract. In early case series, renal stone formation was frequent, whereas the proportion of patients with symptomatic renal stones has declined in recent years. However, a substantial proportion of patients presents with asymptomatic nephrocalcinosis or nephrolithiasis. Before diagnosis and treatment of primary hyperparathyroidism, renal stone events are more frequent than in the general population. However, even after surgical cure, an increased rate of renal stone events may be seen. This may to some extent be the result of stones or calcifications already present at the time of diagnosis or sequelae to prior stones such as infections or ureter strictures. PMID:25911000

  14. Primary Retroperitoneal Mucinous Cystadenoma

    PubMed Central

    Han, Weon Cheol

    2016-01-01

    Mucinous cystadenomas and cystadenocarcinomas of the ovary are clinically and histopathologically well-established common tumors. However, primary retroperitoneal mucinous cystic tumors are extremely rare, and although their histopathogenesis is still uncertain, several theories have been proposed. Most authors suggest that they develop through mucinous metaplasia in a preexisting mesothelium-lined cyst. An accurate preoperative diagnosis of these tumors is difficult because no effective diagnostic measures have been established. Delay in diagnosis and treatment of this tumor may be fatal for the patient because of complications such as rupture, infection, and malignant transformation. We describe the case of a 31-year-old woman with abdominal pain and a palpable mass. Computed tomography of the abdomen revealed a retroperitoneal cystic mass, which was resected successfully through laparoscopy. Histopathological examination of the resected mass confirmed the diagnosis of a primary retroperitoneal mucinous cystadenoma. The patient was discharged on postoperative day 5 without any complications. PMID:26962534

  15. Primary ciliary dyskinesia.

    PubMed Central

    Le Mauviel, L.

    1991-01-01

    Primary ciliary dyskinesia represents a group of heritable disorders of cilia and sperm affecting between 1 in 15,000 and 1 in 30,000 persons. Those affected lack measurable mucociliary clearance and suffer the constant misery of rhinorrhea and chronic productive cough. Because mucociliary clearance constitutes one of the respiratory system's major lines of defense, these patients are vulnerable to chronic sinusitis, bronchitis, pneumonia, and otitis media. Left untreated, these problems may progress to bronchiectasis, found frequently in adult patients, or pulmonary hypertension with eventual cor pulmonale. Screening for this disorder includes some simple and inexpensive methods as well as more exotic techniques requiring special camera equipment and an electron microscope to make a definitive diagnosis. Physiotherapy techniques can be taught to patients with primary ciliary dyskinesia and go a long way toward making up for the lack of mucociliary clearance. Vigorous bronchopulmonary toilet and palliative measures may enable these patients to enjoy relatively normal lives. PMID:1949776

  16. Primary Sclerosing Cholangitis.

    PubMed

    Lee, Young-Mee; Kim, David J.

    2001-12-01

    There is no proven medical therapy for primary sclerosing cholangitis. The goal of management should be treatment of symptoms and complications of cholestasis, as well as attempts at treating the underlying disease process. In addition, efforts should be made to recognize and treat or prevent the known complications of primary sclerosing cholangitis, such as fat-soluble vitamin deficiency, osteopenia, dominant biliary strictures, and cholangiocarcinoma. Although some medical therapy has been shown to improve serum liver test or histology results, there has been no effect on survival or time to liver transplantation. However, preliminary data on high-dosage ursodeoxycholic acid have been encouraging. Liver transplantation remains the only effective treatment and is recommended for patients with end-stage liver disease and symptomatic portal hypertension, liver failure, and recurrent or intractable bacterial cholangitis. PMID:11696273

  17. [Basics of primary immunodeficiencies].

    PubMed

    Hernández-Martínez, Claudia; Espinosa-Rosales, Francisco; Espinosa-Padilla, Sara Elva; Hernández-Martínez, Ana Rosa; Blancas-Galicia, Lizbeth

    2016-01-01

    Primary immunodeficiencies (PID) are a heterogeneous group of inherited disorders, the etiology are the defects in the development or function of the immune system. The principal PID manifestations are the infections in early age, malignancy and diseases of immune dysregulation as autoimmunity and allergy. PIDs are genetics disorders and most of them are inherited as autosomal recessive, also this group of diseases is more prevalent in males and in childhood. The antibody immunodeficiency is the PID more common in adults. The more frequent disorders are the infections in the respiratory tract, abscesses, candidiasis, diarrhea, BCGosis etc. Initial approach included a complete blood count and quantification of immunoglobulins. The delay