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1.
BMC Ophthalmol ; 22(1): 40, 2022 Jan 28.
Article in English | MEDLINE | ID: mdl-35090415

ABSTRACT

BACKGROUND: To analyse ophthalmic presentations to an outer metropolitan and a rural emergency department (ED) during the first wave of the COVID-19 pandemic in New South Wales (NSW), Australia. METHODS: A retrospective comparative study of ophthalmic emergency presentations to Campbelltown Hospital (fifth busiest NSW metropolitan ED; population 310,000) and Bowral and District Hospital (rural ED; population 48,000) before and during COVID-19 was conducted. Patient demographics, triage category, referral source, diagnosis, length of stay, departure status, and follow-up location were assessed from coding data between March 1st to May 31st in 2019 and 2020, corresponding to the peak case numbers and restrictions during the first wave of the COVID-19 pandemic in NSW. Differences before and during COVID-19 were analysed using chi-squared tests or independent sample t-tests. RESULTS: There was no change in ophthalmic presentations at Campbelltown (n = 228 in 2019 vs. n = 232 in 2020; + 1.75%, p = 0.12) and an increase at Bowral (n = 100 in 2019 vs. n = 111 in 2020; + 11%, p < 0.01) during COVID-19. Urgent ophthalmic presentations (Triage Category 3) decreased at Bowral (p = 0.0075), while non-urgent ophthalmic presentations (Triage Category 5) increased at both hospitals (Campbelltown p < 0.05, Bowral p < 0.01). CONCLUSIONS: There was no change in the total number of ophthalmic presentations to an outer metropolitan and an increase to a rural ED during the first wave of the COVID-19 pandemic in New South Wales, Australia. A change in the type of ophthalmic presentations at these peripheral EDs suggest that a high demand for ophthalmic services remained despite the pandemic and its associated gathering and movement restrictions. A flexible healthcare delivery strategy, such as tele-ophthalmology, may optimise patient care during and after COVID-19.


Subject(s)
COVID-19 , Pandemics , Australia , Emergency Service, Hospital , Humans , Retrospective Studies , SARS-CoV-2
2.
Clin Exp Optom ; 103(2): 201-206, 2020 03.
Article in English | MEDLINE | ID: mdl-31218754

ABSTRACT

BACKGROUND: Previous research has shown that cataract surgery referral letters to major metropolitan public hospitals in New South Wales have insufficient detail to inform patient triage or apply prioritisation tools. This study aimed to canvass the views of optometrists working in New South Wales and the Australian Capital Territory (NSW/ACT) on standardising the referral process for public hospital cataract surgery. METHODS: An online survey was sent to all NSW/ACT members of Optometry Australia in October 2017. Respondents were asked to select clinical and personal information to be included on a referral template using a list of 25 items. Data were also gathered on preferences for the cataract referral process and sources of cataract referral guidelines. RESULTS: Two hundred and thirteen (response rate 13 per cent) optometrists completed the survey. There was close to universal support for inclusion of items like visual acuity (99 per cent), whereas other items had low support, including the date and details of previous refraction (26 per cent), history of falls (29 per cent) and health insurance status (29 per cent). Three-quarters of optometrists stated they would be willing to administer and report data from a patient survey about the functional impact of their cataract and level of visual disability. The preferred format of a standardised cataract referral template varied, although time efficiency and ease of completion were commonly cited reasons for preferences. Confirmation of receipt of referral from the public hospital, and a copy of the referral letter for the optometrist's records were also desirable. For the 61 per cent of respondents who reported accessing guidelines for cataract referral, 69 per cent stated the main source was Optometry NSW/ACT with fewer accessing guidelines directly from a public hospital or the NSW Health website. CONCLUSION: Optometrists' preferences will be useful to inform the design and implementation of a standardised cataract referral template.


Subject(s)
Cataract/therapy , Hospitals, Public/statistics & numerical data , Optometrists/standards , Referral and Consultation/standards , Cataract/diagnosis , Cataract/epidemiology , Cross-Sectional Studies , Humans , Incidence , Morbidity/trends , New South Wales/epidemiology , Retrospective Studies , Surveys and Questionnaires
3.
Life Sci ; 239: 117073, 2019 Dec 15.
Article in English | MEDLINE | ID: mdl-31751581

ABSTRACT

AIMS: Recently, strategies of cancer treatment using combination of agents with distinct molecular mechanism(s) of action are considered more promising due to its high efficacy and reduced systemic toxicity. The study is aimed to improve the efficacy of selective estrogen receptor modulator, Centchroman (CC) by combination with the phytoestrogen Genistein (GN). METHODS: Cytotoxicity was evaluated by Sulforhodamine B assay. Cell cycle analysis was done through flow cytometry. Further, Apoptosis was analyzed using Annexin V/PI staining, tunel assay and electron microscopic examination and verified using western blot analysis. In order to validate the in vitro results, in vivo analysis was performed using 4T1-syngeneic mouse model. KEY FINDINGS: In this study, we report that the dietary isoflavone genistein (GN) synergistically improved antineoplasticity of CC in breast cancer by arresting cells at G2/M phase culminating in ROS dependent apoptosis. The combination of CC plus GN caused dysregulation of Bax and Bcl-2 ratio inducing mitochondrial dysfunction, activation of Caspase-3/7, -9 and PARP cleavage. Further, combination significantly suppresses phosphorylation of PI3K/Akt/NF-κB, enhancing apoptosis. Additionally, combination markedly reduced tumor growth compared to CC and GN alone in mouse 4T1 breast tumor model. SIGNIFICANCE: Together, these studies suggest that GN represents a potential adjunct molecule whose role in CC induced apoptosis deserves attention.


Subject(s)
Breast Neoplasms/metabolism , Centchroman/pharmacology , Genistein/pharmacology , Animals , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Cell Cycle/drug effects , Cell Line, Tumor , Cell Survival/drug effects , Centchroman/metabolism , Drug Synergism , Female , Genistein/metabolism , Humans , Isoflavones/pharmacology , MCF-7 Cells , Membrane Potential, Mitochondrial/drug effects , Mice , Mice, Inbred BALB C , Phosphatidylinositol 3-Kinases/metabolism , Phytoestrogens/pharmacology , Proto-Oncogene Proteins c-akt/metabolism , Reactive Oxygen Species/metabolism , Signal Transduction/drug effects
4.
Phytomedicine ; 40: 116-124, 2018 Feb 01.
Article in English | MEDLINE | ID: mdl-29496164

ABSTRACT

BACKGROUND: Despite advancements in the prognosis and management of breast cancer, it remains a major cause of mortality in women worldwide. Centchroman (CC), an oral contraceptive has been found to exhibit anti-cancer potential against a wide range of cancer including breast cancer. PURPOSE: The present study is intended to evaluate the ability of soy isoflavone Daidzein (DZ) in enhancing the efficacy of CC in Human Breast Cancer Cells (HBCCs). METHODS/STUDY DESIGN: Sulforhodamine B assay was employed to determine the cytotoxicity induced by 10 µM CC & 50 µM DZ separately and together in MCF-7/MDA MB-231 HBCCs and non-tumorigenic Human Mammary Epithelial Cells (HMECs) MCF-10A as a control. Combination Index (CI) analysis was executed using CompuSyn software. Further, apoptosis was assessed using Annexin V/PI, AO/PI staining and tunel assay. Cell cycle, reactive oxygen species generation and mitochondrial membrane potential alteration was determined using flow cytometry. Western blot analysis was performed to check the expression of respective proteins. RESULTS: The results suggest that the combination exerts elevated toxicity as compared to control and each drug per se without affecting HMECs MCF-10A. This therefore implies cancer cell specific action of CC plus DZ administered together. Additionally, combination index analysis suggests synergistic action of CC and DZ combination in HBCCs. Cell cycle analysis, Annexin V/PI staining, tunel assay and western blot analysis confirms the induction of apoptosis by combination in HBCCs. Interestingly, western blot analysis also revealed that the combination down-regulated the expression of proteins involved in cell survival i.e. PI3K, Akt and mTOR, suggesting inhibition of cell survival pathway. CONCLUSION: The results overall demonstrate that CC plus DZ has higher anticancer efficacy as compared to either drug alone. Hence, the combination of CC plus DZ may offer a novel strategy for the management of breast cancer.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/pharmacology , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Apoptosis/drug effects , Breast Neoplasms/pathology , Cell Cycle/drug effects , Cell Line, Tumor , Cell Survival/drug effects , Centchroman/administration & dosage , Centchroman/pharmacology , Drug Synergism , Female , Humans , Isoflavones/administration & dosage , Isoflavones/pharmacology , MCF-7 Cells , Membrane Potential, Mitochondrial/drug effects , TOR Serine-Threonine Kinases/metabolism
5.
Nanomedicine ; 14(2): 327-337, 2018 02.
Article in English | MEDLINE | ID: mdl-29129754

ABSTRACT

Lapatinib (LPT) is an orally administered drug for the treatment of metastatic breast cancer. For expanding its therapeutic horizon, we have prepared its nanocrystals (LPT-NCs) that were subsequently coated with hyaluronic acid (HA) to produce LPT-HA-NCs. The detailed in-vitro and in-vivo investigation of LPT-HA-NCs showed the superior anticancer activity due to active targeting to CD44 receptors than the counterparts LPT-NCs and free LPT. In the triple negative 4T1 cells induced breast tumor bearing female Balb/C mice; LPT-HA-NCs treatment caused significant retardation of tumor growth and overall increase in animal survival probability because of their higher tumor localization, increased residence time. Our findings clearly suggest that HA coated LPT-NCs formulation enhances the activity of LPT against triple negative breast cancer. It exhibited magnificent therapeutic outcome at low dose thus presenting a strategy to reduce dose administrations and minimize dose related toxicity.


Subject(s)
Antineoplastic Agents/pharmacology , Hyaluronan Receptors/antagonists & inhibitors , Hyaluronic Acid/chemistry , Lapatinib/pharmacology , Nanoparticles/chemistry , Triple Negative Breast Neoplasms/drug therapy , Animals , Antineoplastic Agents/chemistry , Female , Lapatinib/chemistry , Mice , Mice, Inbred BALB C , Triple Negative Breast Neoplasms/metabolism , Triple Negative Breast Neoplasms/pathology , Tumor Cells, Cultured , Xenograft Model Antitumor Assays
6.
Life Sci ; 193: 9-19, 2018 Jan 15.
Article in English | MEDLINE | ID: mdl-29196053

ABSTRACT

AIMS: Angiogenesis is a recognized hallmark of cancer which promotes cancer cell progression and metastasis. Inhibition of angiogenesis to attenuate cancer growth is becoming desirable strategy for breast cancer management. The present study is aimed to investigate the antiangiogenic efficacy of a novel selective estrogen receptor modulator Centchroman (CC) on human breast cancer cells. MAIN METHODS: Effect of CC on cell viability was evaluated using Sulforhodamine B assay. Endothelial cell proliferation, wound healing, Boyden chamber cell invasion, tube formation and chorioallantoic membrane (CAM) assays were performed to assess the effect of CC on migration, invasion and angiogenesis. Apoptosis, reactive oxygen species generation, caspase-3/7 and intracellular calcium ion level were measured through flow cytometry. Expression levels of HIF-1α, VEGF, VEGFR2, AKT and ERK were assessed by western blot analysis. KEY FINDINGS: CC selectively induces apoptosis in human breast cancer cells without affecting non-tumorigenic breast epithelial cells MCF-10A. Moreover, it inhibits migratory, invasive and mammosphere forming potential of breast cancer. Furthermore, CC also inhibited VEGF-induced migration, invasion and tube formation of HUVECs in vitro. CC effectively inhibited neovasculature formation in chicken CAM. Western blot analysis demonstrated that CC inhibited expression of HIF-1α and its downstream target VEGF. Interestingly, CC also suppressed VEGFR2 phosphorylation and consequently attenuated AKT and ERK phosphorylation. SIGNIFICANCE: Our findings suggest that CC downregulates VEGF-induced angiogenesis by modulating HIF-1α/VEGFR2 pathway and recommend it (CC) as a potential therapeutic drug for breast cancer treatment.


Subject(s)
Centchroman/metabolism , Centchroman/therapeutic use , Angiogenesis Inducing Agents , Angiogenesis Inhibitors/pharmacology , Apoptosis , Breast/metabolism , Breast Neoplasms/metabolism , Cell Hypoxia/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Female , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , MAP Kinase Signaling System , Neovascularization, Pathologic/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction/drug effects , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor Receptor-2/metabolism
7.
Pharmacogn Mag ; 13(51): 345-350, 2017.
Article in English | MEDLINE | ID: mdl-28839355

ABSTRACT

OBJECTIVE: This study aimed to investigate the cytotoxicity, apoptosis induction, and mechanism of action of steviol on human breast cancer cells (Michigan Cancer Foundation-7 [MCF-7]). MATERIALS AND METHODS: Sulforhodamine-B assay was performed to analyze cytotoxic potential of Steviol whereas flow cytometer was used to analyze cell cycle, apoptosis, and reactive oxygen species generation. RESULTS: Studying the viability of cells confirms the IC50 of Steviol in MCF-7 cells which was 185 µM. The data obtained from fluorescence-activated cell sorter analysis reveal Steviol-mediated G2/M-phase arrest (P < 0.05) in addition to the presence of evident sub-G0/G1 peak (P < 0.05) in the MCF-7 cells, signifying the ongoing apoptosis. CONCLUSION: Thus, results suggest that induction of apoptosis in MCF-7 cells was due to dose-dependent effect of Steviol. Our first in vitro findings indicate Steviol as a promising candidate for the treatment of breast cancer. SUMMARY: Steviol remarkably inhibited the growth MCF-7 HBCCs in a dose dependent mannerIt abolishes cell cycle progression by arresting cells at G2/M phaseSteviol induces the cells to undergo apoptosisSteviol induces the cells to generate reactive oxygen species (ROS). Abbreviations used: MCF-7: Michigan Cancer Foundation-7; SRB: Sulforhodamine-B assay; FACS: Fluorescence-activated cell sorter; ROS: Reactive oxygen species; DNA: Deoxyribonucleic acid.

8.
Asian Pac J Cancer Prev ; 18(8): 2135-2140, 2017 08 27.
Article in English | MEDLINE | ID: mdl-28843234

ABSTRACT

Background: In traditional Indian medicine, azadirachta indica (neem) is known for its wide range of medicinal properties. Various parts of neem tree including its fruit, seed, bark, leaves, and root have been shown to possess antiseptic, antiviral, antipyretic, anti-inflammatory, antiulcer, antimalarial, antifungal and anticancer activity. Materials and Methods: MCF-7 and MDA MB-231 cells were exposed to various concentrations of 2% ethanolic solution of NSO (1-30 µl/ml) and further processed for cell viability, cell cycle and apoptosis analysis. In addition, cells were analyzed for alteration in Mitochondrial Membrane Potential (MMP) and generation of Reactive Oxygen Species (ROS) using JC-1 and DCFDA staining respectively. Results: NSO give 50% inhibition at 10 µl/ml and 20 µl/ml concentration in MCF-7 and MDA MB-231 cells respectively and, arrests cells at G0/G1 phase in both the cell types. There was a significant alteration in mitochondrial membrane potential that leads to the generation of ROS and induction of apoptosis in NSO treated MCF-7 and MDA MB-231 cells. Conclusion: The results showed that NSO inhibits the growth of human breast cancer cells via induction of apoptosis and G1 phase arrest. Collectively these results suggest that NSO could potentially be used in the management of breast cancer.

9.
Apoptosis ; 22(4): 570-584, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28176146

ABSTRACT

Centchroman (CC) or Ormeloxifene has been shown to induce apoptosis and cell cycle arrest in various types of cancer cells. This has, however, not been addressed for endometrial cancer cells where its (CC) mechanism of action remains unclear. This study focuses on the basis of antineoplasticity of CC by blocking the targets involved in the cell cycle, survival and apoptosis in endometrial cancer cells. Ishikawa Human Endometrial Cancer Cells were cultured under estrogen deprived medium, exposed to CC and analyzed for proliferation and apoptosis. Additionally, we also analyzed oxidative stress induced by CC. Cell viability studies confirmed the IC50 of CC in Ishikawa cells to be 20 µM after 48 h treatment. CC arrests the cells in G0/G1 phase through cyclin D1 and cyclin E mediated pathways. Phosphatidylserine externalization, nuclear morphology changes, DNA fragmentation, PARP cleavage, and alteration of Bcl-2 family protein expression clearly suggest ongoing apoptosis in the CC treated cells. Activation of caspase 3 & 9, up-regulation of AIF and inhibition of apoptosis by z-VAD-fmk clearly explains the participation of the intrinsic pathway of programmed cell death. Further, the increase of ROS, loss of MMP, inhibition of antioxidant (MnSOD, Cu/Zn-SOD and GST) and inhibition of apoptosis with L-NAC suggests CC induced oxidative stress leading to apoptosis via mitochondria mediated pathway. Therefore, CC could be a potential therapeutic agent for the treatment of Endometrial Cancer adjunct to its utility as a contraceptive and an anti-breast cancer agent.


Subject(s)
Adenocarcinoma/pathology , Antineoplastic Agents, Hormonal/pharmacology , Apoptosis/drug effects , Cell Cycle Checkpoints/drug effects , Centchroman/pharmacology , Endometrial Neoplasms/pathology , Caspases/physiology , Cell Cycle Proteins/metabolism , Cell Line, Tumor , Cyclin D1/physiology , Cyclin E/physiology , DNA Fragmentation/drug effects , Female , Humans , Inhibitory Concentration 50 , MAP Kinase Signaling System/drug effects , MAP Kinase Signaling System/physiology , Membrane Potential, Mitochondrial/drug effects , Neoplasm Proteins/physiology , Oxidation-Reduction , Protein Transport/drug effects
10.
Indian J Pharmacol ; 48(6): 637-642, 2016.
Article in English | MEDLINE | ID: mdl-28066099

ABSTRACT

OBJECTIVES: Despite the progress in the diagnosis and treatment of breast cancer, it remains a major health problem in women. Natural flavones along with chemotherapeutic agents enhance therapeutic response and minimize toxicity of chemical agents. Centchroman (CC) colloquially called as ormeloxifene, is a nonsteroidal oral contraceptive categorized as selective estrogen receptor modulator with anti-breast cancer activity. Genistein (GN), an isoflavone found mainly in soy products possesses anti-cancerous potential against a number of cancers including breast. The present study aims at investigating the combination of CC and GN in human breast cancer cell lines (HBCCs). MATERIALS AND METHODS: Cytotoxic effect of CC and GN separately and in combination were assessed by sulforhodamine B (SRB) assay in MDA MB-231, MDA MB-468, MCF-7, T-47D HBCCs, and nontumorigenic human mammary epithelial cell (HMEC) MCF-10A. The drug interaction was analyzed using CompuSyn software through which combination index and dose reduction index were generated. RESULTS: Combination of CC plus GN exerts significantly higher cytotoxicity compared to each drug per se in HBCCs, whereas HMEC-MCF-10A remains unaffected. CONCLUSION: On an overall basis, the drugs in combination enhanced cell killing in malignant cells. Therefore, the combination of CC with GN may offer a novel approach for the breast cancer.


Subject(s)
Anticarcinogenic Agents/administration & dosage , Breast Neoplasms , Centchroman/administration & dosage , Estrogen Antagonists/administration & dosage , Genistein/administration & dosage , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Cell Line, Tumor , Cell Survival/drug effects , Cell Survival/physiology , Dose-Response Relationship, Drug , Drug Synergism , Drug Therapy, Combination , Female , Growth Inhibitors/administration & dosage , Humans , MCF-7 Cells
12.
J Thromb Thrombolysis ; 35(2): 250-6, 2013 Feb.
Article in English | MEDLINE | ID: mdl-22918664

ABSTRACT

In the present study, an attempt is made to understand the role of genetic thrombophilias i.e. MTHFR C677T and FVL in the causation of various pregnancy complications like pregnancy induced hypertension (PIH), recurrent abortions, intra-uterine growth retardation (IUGR) and intra-uterine death on the whole and also individually along with the comparative assessment of pathophysiological basis of various pregnancy complications via the genetic proximities. One thousand and eleven (1,011) women of reproductive age group were recruited in the present study comprising various complications and controls. Recruitment criteria for all the pregnancy complications and controls was made and followed strictly. MTHFR C677T and FVL mutation detection was done in all the subjects. Vegetarianism was found to be significant risk factors for all the pregnancy complications and also when assessed individually. With respect to MTHFR C677T polymorphism, higher frequency of 677T allele was found among controls as compared to cases. 677T allele was found to pose decreased risk for various pregnancy complications on the whole and also individually. On adjusting the diet, regression analysis revealed no risk of mutant allele (T) for various pregnancy complications. FVL homozygous mutants were found to be absent among controls. In conclusion, the present study depicts dietary pattern as one of the most important factors in demonstrating the role of MTHFR C677T in various pregnancy complications and is indicative of a relatively deleterious effect of double dose of FVL in the presently studied population. Additionally, these polymorphisms play an important role in the orchestration of PIH to IUGR and vice versa.


Subject(s)
Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Polymorphism, Genetic/genetics , Pregnancy Complications, Hematologic/ethnology , Pregnancy Complications, Hematologic/genetics , Thrombophilia/ethnology , Thrombophilia/genetics , Adult , Case-Control Studies , Diet, Vegetarian/adverse effects , Diet, Vegetarian/ethnology , Female , Humans , India/ethnology , Pregnancy , Pregnancy Complications, Hematologic/diagnosis , Thrombophilia/diagnosis , Young Adult
13.
AIDS Res Hum Retroviruses ; 29(3): 501-10, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23131038

ABSTRACT

In HIV-1 infection, plasmacytoid dendritic cell (PDC) numbers and function are decreased. No detailed comparisons of PDC responses to various stimuli in HIV-1-infected patients are available. Using for the first time purified PDCs, we compared PDC responses [interferon (IFN)-α production/cell] to various stimuli in a large number (n=48) of HIV-1-infected patients and healthy volunteers (n=19). Toll-like receptor (TLR)7- and TLR9-induced expression of PDC surface activation and maturation markers was also compared in the two populations. We have confirmed that PDC number coincides with CD4(+) T cell counts and clinical state. Notably, we have shown that a direct association of PDC function in terms of IFN-α production/cell exists with PDC numbers and CD4(+) cell counts when PDCs are exposed to a TLR9 ligand and HIV-infected cells, but not with a TLR7 ligand. Moreover, in the HIV-infected subjects but not the healthy controls, the magnitude of IFN-α release per PDC in response to the TLR7 ligand is significantly (p<0.01) lower than that to the TLR9 ligand. However, in both study populations, the TLR7 stimulation in comparison to TLR9 stimulation induced higher expression of PDC surface activation and maturation markers and significantly (p<0.05) decreased the expression of BDCA-2, a negative regulator of interferon. Furthermore, the cross-ligation of BDCA-2 significantly (p<0.05) inhibited TLR9- but not TLR7-induced IFN-α production by PDCs from both clinical groups. These findings suggest that differences exist in TLR7- and TLR9-induced IFN-α production by PDCs in HIV-infected individuals that are not directly related to BDCA-2 down-modulation.


Subject(s)
Dendritic Cells/immunology , HIV Infections/immunology , HIV-1/pathogenicity , Toll-Like Receptor 7/agonists , Toll-Like Receptor 9/agonists , Adult , Aged , CD4-Positive T-Lymphocytes/immunology , Female , HIV Infections/pathology , Humans , Interferon-alpha/metabolism , Lectins, C-Type/biosynthesis , Leukocyte Count , Male , Membrane Glycoproteins/biosynthesis , Middle Aged , Receptors, Immunologic/biosynthesis , Toll-Like Receptor 7/immunology , Toll-Like Receptor 9/immunology
15.
Ophthalmology ; 119(11): 2298-303, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22959104

ABSTRACT

OBJECTIVE: To clarify possible associations between cataract surgery and progression of age-related macular degeneration (AMD). DESIGN: Clinic-based cohort. PARTICIPANTS: We followed cataract surgical patients aged 65+ years in the Australian Cataract Surgery and Age-related Macular Degeneration (CSAMD) study. Patients who remained unilaterally phakic for at least 24 months after recruitment were included. METHODS: We performed annual examinations with retinal photography. We assessed AMD using side-by-side grading of images from all visits. Paired comparisons between operated and nonoperated fellow eyes (defined as nonoperated or operated <12 months previously) were made using generalized estimating equation models. MAIN OUTCOME MEASURES: Incident early AMD was defined as the new appearance of soft indistinct/reticular drusen or coexisting retinal pigmentary abnormality and soft distinct drusen in eyes at risk of early AMD. Incident late AMD was defined as the new appearance of neovascular AMD or geographic atrophy (GA) in eyes at risk of late AMD. RESULTS: Among 2029 recruited, eligible participants, 1851 had cataract surgery performed at Westmead Hospital, Sydney, and 1244 (70.7%) had 36-month postoperative visits. Of these participants, 1178 had gradable photographs at baseline and at least 1 follow-up visit. Of 308 unilaterally operated participants at risk of late AMD, this developed in 4 (1.3%) operated and 7 (2.3%) nonoperated fellow eyes (odds ratio [OR], 0.74; 95% confidence interval [CI], 0.23-2.36) after adjusting for the presence of early AMD at baseline. Of 217 unilaterally operated participants at risk of early AMD, this developed in 23 (10.6%) operated and 21 (9.7%) nonoperated fellow eyes (OR, 1.07; 95% CI, 0.74-1.65). Incident retinal pigment abnormalities were more frequent in operated than nonoperated fellow eyes (15.3% vs. 9.9%; OR, 1.64; 95% CI, 1.07-2.52). There was no difference in the 3-year incidence of large soft indistinct or reticular drusen between the 2 eyes (8.8% vs. 7.9%; OR, 1.12; 95% CI, 0.79-1.60). CONCLUSIONS: Prospective follow-up data and paired eye comparisons of this older surgical cohort showed no increased risk of developing late AMD, early AMD, or soft/reticular drusen over 3 years. There was a 60% increased detection of retinal pigmentary changes in surgical eyes.


Subject(s)
Cataract Extraction/statistics & numerical data , Geographic Atrophy/epidemiology , Wet Macular Degeneration/epidemiology , Aged , Cardiomyopathies/epidemiology , Cohort Studies , Disease Progression , Female , Follow-Up Studies , Geographic Atrophy/diagnosis , Geographic Atrophy/etiology , Humans , Hypercholesterolemia/epidemiology , Hypertension/epidemiology , Incidence , Male , New South Wales/epidemiology , Photography , Prospective Studies , Risk Assessment , Smoking/epidemiology , Time Factors , Wet Macular Degeneration/diagnosis , Wet Macular Degeneration/etiology
17.
J Am Geriatr Soc ; 57(10): 1892-6, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19737331

ABSTRACT

OBJECTIVES: To examine the association between retinal microvascular signs, as a proxy for cerebral microvascular disease, and cognitive impairment. DESIGN: Cross-sectional population-based study. SETTING: Urban population survey PARTICIPANTS: One thousand nine hundred eighty-eight persons aged 49 to 97. MEASUREMENTS: All participants underwent retinal photography and had the Mini-Mental State Examination (MMSE) administered by trained personnel. Retinal photographs were masked and graded for retinopathy signs (microaneurysms, hemorrhages, hard exudates, cotton wool spots), and retinal vessel calibers were measured using a validated computer-assisted method. Cognitive impairment was defined as an MMSE score of 23 or less, in line with other epidemiological studies. RESULTS: Cognitive impairment was present in 121 participants (6.1%). In the total population, after adjusting for age, sex, blood pressure, diabetes mellitus, smoking, cardiovascular disease, education, and other factors, retinal venular dilation was associated with cognitive impairment (odds ratio (OR)=1.8, 95% confidence interval (95% CI)=1.0-3.2, P=.03). In persons with hypertension, retinopathy signs (adjusted OR=1.7, 95% CI=1.0-3.2, P=.05) and retinal venular dilation (adjusted OR=2.7, 95% CI=1.2-6.1, P=.01) were associated with cognitive impairment. CONCLUSION: Retinal microvascular signs are associated with significant cognitive impairment, particularly in older persons with hypertension. These findings suggest that cerebral microvascular changes may contribute to cognitive deterioration.


Subject(s)
Cognition Disorders/etiology , Microvessels , Retinal Vessels , Vascular Diseases/complications , Aged , Cerebrovascular Disorders/complications , Cerebrovascular Disorders/diagnosis , Cross-Sectional Studies , Female , Humans , Male , Vascular Diseases/diagnosis
18.
Med Microbiol Immunol ; 198(1): 47-56, 2009 Feb.
Article in English | MEDLINE | ID: mdl-18985383

ABSTRACT

Cytotoxic T lymphocyte (CTL) responses to Gag have been most frequently linked to control of viremia whereas CTL responses to Nef have direct relationship with viral load. IFN-gamma ELISpot assay was used to screen CTL responses at single peptide level directed at HIV-1 subtype C Gag and Nef proteins in 30 antiretroviral therapy naive HIV-1 infected Indian individuals. PBMCs from 73.3% and 90% of the study population showed response to Gag and Nef antigens, respectively. The magnitude of Gag-specific CTL responses was inversely correlated with plasma viral load (r = -0.45, P = 0.001), whereas magnitude of Nef-specific responses was directly correlated (r = 0.115). Thirteen immunodominant regions (6 in Gag, 7 in Nef) were identified in the current study. The identification of Gag and Nef-specific responses across HIV-1 infected Indian population and targeting epitopes from multiple immunodominant regions may provide useful insight into the designing of new immunotherapy and vaccines.


Subject(s)
HIV Infections/immunology , HIV Infections/virology , HIV-1/immunology , T-Lymphocytes, Cytotoxic/immunology , Viral Load , gag Gene Products, Human Immunodeficiency Virus/immunology , nef Gene Products, Human Immunodeficiency Virus/immunology , Adult , Cells, Cultured , Enzyme-Linked Immunosorbent Assay , Epitopes, T-Lymphocyte/analysis , Female , Humans , Immunodominant Epitopes/analysis , India , Interferon-gamma/metabolism , Male , Peptide Fragments/metabolism , Young Adult
19.
Stroke ; 40(1): 206-12, 2009 Jan.
Article in English | MEDLINE | ID: mdl-18948616

ABSTRACT

BACKGROUND AND PURPOSE: It is unclear whether diets with high glycemic index (GI) and low cereal fiber (CF) are associated with greater risk of stroke. We aimed to assess the relationship between dietary GI and CF content, retinal microvasculature changes, and stroke-related mortality. METHODS: The study consisted of a population-based cohort, 49+ years, examined at baseline (1992 to 1994). At baseline, participants completed validated food frequency questionnaires. Mean GI was calculated using an Australian database. Retinal arteriolar and venular diameters were measured from photographs. Mortality data were derived using the Australian National Death Index. RESULTS: Over 13 years, 95 of 2897 participants (3.5%) died from stroke. Increasing GI (hazard ratio, 1.91; 95% CI, 1.01 to 3.47, highest versus lowest tertile) and decreasing CF (hazard ratio, 2.13; 95% CI, 1.19 to 3.80, lowest versus highest tertile) predicted greater risk of stroke death adjusting for multiple stroke risk factors. Persons consuming food in the highest GI tertile and lowest CF tertile had a 5-fold increased risk of stroke death (hazard ratio, 5.06; 95% CI, 1.67 to 15.22). Increasing GI and decreasing CF were also associated with retinal venular caliber widening (P(trend)<0.01). Adjustment for retinal venular caliber attenuated stroke death risk associated with high GI by 50% but did not affect the risk associated with low CF consumption. CONCLUSIONS: High-GI and low-CF diets predict greater stroke mortality and wider retinal venular caliber. The association between a high-GI diet and stroke death was partly explained by GI effects on retinal venular caliber, suggesting that a high-GI diet may produce deleterious anatomic changes in the microvasculature.


Subject(s)
Diabetic Retinopathy/epidemiology , Dietary Carbohydrates/adverse effects , Food, Formulated/adverse effects , Glycemic Index/physiology , Hyperglycemia/epidemiology , Stroke/mortality , Aged , Australia/epidemiology , Cohort Studies , Diabetes Mellitus/blood , Diabetes Mellitus/epidemiology , Diabetes Mellitus/physiopathology , Diabetic Retinopathy/blood , Diabetic Retinopathy/physiopathology , Dietary Carbohydrates/blood , Female , Humans , Hyperglycemia/blood , Hyperglycemia/physiopathology , Male , Middle Aged , Odds Ratio , Proportional Hazards Models , Retinal Artery/pathology , Retinal Artery/physiopathology , Retinal Vein/pathology , Retinal Vein/physiopathology , Risk Factors , Stroke/blood , Stroke/physiopathology , Surveys and Questionnaires
20.
Am J Clin Nutr ; 88(4): 1104-10, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18842800

ABSTRACT

BACKGROUND: Dietary factors are known risk factors for age-related macular degeneration (AMD) -- the leading cause of visual loss among persons aged > or =65 y. High-glycemic-index diets have been hypothesized as a risk factor for AMD, but prospective data are unavailable. OBJECTIVE: The objective was to examine the association between dietary glycemic index and the 10-y incidence of AMD in the Blue Mountain Eye Study population. DESIGN: This was a population-based cohort study with 3,654 participants (> or =49 y) examined at baseline (1992-1994); 2,335 patients were reexamined after 5 y and 1952 after 10 y. The Wisconsin System was used to grade 10-y incident early and late AMD from retinal photographs. A food-frequency questionnaire was used to collect dietary information at baseline, and an Australian database was used to calculate the mean glycemic index. RESULTS: Over 10 y, 208 of 1,810 persons (cumulative incidence: 14.1%) developed early AMD. After age, smoking, other risk factors, and dietary constituents were adjusted for, a higher mean dietary glycemic index was associated with an increased 10-y risk of early AMD in a comparison of quartiles 1 and 4 [relative risk (RR): 1.77; 95% CI: 1.13, 2.78; P for trend = 0.03]. Conversely, a greater consumption of cereal fiber (RR: 0.68; 95% CI: 0.44, 1.04; P for trend = 0.05) and breads and cereals (predominantly lower glycemic index foods such as oatmeal) (RR: 0.67; 95% CI: 0.44, 1.02; P for trend = 0.03) was associated with a reduced risk of incident early AMD. No relation was observed with late AMD. CONCLUSIONS: A high-glycemic-index diet is a risk factor for early AMD -- the recognized precursor of sight-threatening late AMD. Low-glycemic-index foods such as oatmeal may protect against early AMD.


Subject(s)
Dietary Carbohydrates/administration & dosage , Dietary Fiber/administration & dosage , Feeding Behavior , Glycemic Index , Macular Degeneration/epidemiology , Aged , Cohort Studies , Dietary Carbohydrates/classification , Dietary Carbohydrates/metabolism , Dietary Fiber/classification , Dietary Fiber/metabolism , Female , Follow-Up Studies , Humans , Incidence , Macular Degeneration/etiology , Macular Degeneration/prevention & control , Male , Middle Aged , Multivariate Analysis , New South Wales/epidemiology , Prospective Studies , Risk Factors , Surveys and Questionnaires
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