Marian R. Fisher

Bio: Marian R. Fisher is an academic researcher from University of Wisconsin-Madison. The author has contributed to research in topics: Macular edema & Diabetic retinopathy. The author has an hindex of 19, co-authored 26 publications receiving 5270 citations.

Effects of Torcetrapib in Patients at High Risk for Coronary Events

Abstract: Background Inhibition of cholesteryl ester transfer protein (CETP) has been shown to have a substantial effect on plasma lipoprotein levels. We investigated whether torcetrapib, a potent CETP inhibitor, might reduce major cardiovascular events. The trial was terminated prematurely because of an increased risk of death and cardiac events in patients receiving torcetrapib. Methods We conducted a randomized, double-blind study involving 15,067 patients at high cardiovascular risk. The patients received either torcetrapib plus atorvastatin or atorvastatin alone. The primary outcome was the time to the first major cardiovascular event, which was defined as death from coronary heart disease, nonfatal myocardial infarction, stroke, or hospitalization for unstable angina. Results At 12 months in patients who received torcetrapib, there was an increase of 72.1% in high-density lipoprotein cholesterol and a decrease of 24.9% in low-density lipoprotein cholesterol, as compared with baseline (P<0.001 for both compari...

A Randomized Trial Comparing the Efficacy and Safety of Intravitreal Triamcinolone With Observation to Treat Vision Loss Associated With Macular Edema Secondary to Central Retinal Vein Occlusion: The Standard Care vs Corticosteroid for Retinal Vein Occlusion (SCORE) Study Report 5

Abstract: Retinal vein occlusion disease is estimated to be the second most common cause of retinal vascular disease in the United States.1 The prevalence of retinal vein occlusion in the Blue Mountains Eye Study was 1.6%, with 69.5%(41of59)oftheseocclusionsclassified as branch retinal vein occlusion (BRVO).2 Retinal vein occlusion was bilateral in 5.1% of cases.2 The 15-year cumulative incidence of BRVO was 1.8% in the Beaver Dam Eye Study.3 In the Beaver Damcohort,centraland branch retinal vein occlusion accounted for 12% of eyes that developed severe vision loss during a 15-year period.4 Macular edema is a frequent cause of visual acuity loss from BRVO.1,5,6 The natural history of macular edema secondary to BRVO was delineated in the Branch Vein Occlusion Study (BVOS).1 One arm of the BVOS demonstrated a benefit with grid photocoagulation.1 Of 43 treated eyes available for follow-up at the 3-year visit, 28 (65%) had gained 2 or more lines of visual acuity from baseline and maintained this gain for at least 8 months compared with the same gain in 13 of 35 untreated eyes (37%). The BVOS also identified a subset of patients who derived limited benefit from grid photocoagulation. In the BVOS, 40% of treated eyes (n=43) had worse than 20/40 visual acuity at 3 years, and 12% of treated eyes had 20/200 or worse visual acuity at 3 years.1 During the last decade, a number of additional treatments for macular edema secondary to BRVO have been investigated. Such treatments include laser chorioretinal anastomosis, vitrectomy, arteriovenous sheathotomy, and intravitreal injection of antibodies targeted at vascular endothelial growth factor (VEGF).7-12 Numerous reports have suggested that intravitreal injection(s) of triamcinolone acetonide (hereafter referred to as intravit-real triamcinolone) is a potentially efficacious therapy for retinal thickening and vision loss in patients with macular edema secondary to BRVO but that some patients may develop steroid-related complications, such as elevated intraocular pressure (IOP) and cataract.13-26 Most of the information concerning intravitreal triamcinolone for macular edema secondary to BRVO is derived from case series that lacked long-term follow-up and adequate numbers of study participants; a randomized and controlled study has not been performed.13-26 Despite the shortcomings of these case series, intravitreal triamcinolone is currently in use as a treatment for BRVO. The rationale for the use of corticosteroids to treat macular edema secondary to BRVO follows from the observation that the increase in retinal capillary permeability that results in macular edema may be caused by a breakdown of the blood-retina barrier mediated in part by VEGF, a 45-kDa glycoprotein.27-29 Therefore, attenuation of the effects of VEGF may reduce macular edema associated with BRVO.30,31 Corticosteroids have been demonstrated to inhibit the expression of VEGF and therefore may be an effective therapy for macular edema.32,33 Inflammation may also play a role in the pathology of BRVO, and the anti-inflammatory properties of corticosteroids may contribute to the attenuation of the disease process.34 Intravitreal triamcinolone is used by ophthalmologists in the clinical setting as a readily available pharmacologic agent (Kenalog 40; Bristol-Myers Squibb, Princeton, New Jersey, or Triesence; Alcon Inc, Fort Worth, Texas), though use for the treatment of macular edema is off label. Other formulations such as compounded preservative-free triamcinolone acetonide are also used in the clinical setting. The Standard Care vs Corticosteroid for Retinal Vein Occlusion (SCORE) Study, sponsored by the National Eye Institute, is a clinical trial designed to compare 1-mg and 4-mg doses of intravitreal triamcinolone with standard care for vision loss associated with macular edema secondary to per-fused central retinal vein occlusion (CRVO) and BRVO.35,36 This article describes findings from the SCORE-BRVO trial. A companion article that compares intravitreal triamcinolone with observation for vision loss associated with macular edema secondary to CRVO is published concurrently (the SCORE-CRVOtrial).37 The 2 primary study objectives of the SCORE-BRVO trial are (1) to determine whether intravit-real triamcinolone at 1-mg and 4-mg doses produces greater visual benefit, with an acceptable safety profile,than grid photocoagulation, when appropriate, for the treatment of vision loss associated with macular edema secondary to BRVO; and (2) to compare the efficacy and safety of the 1-mg and 4-mg triamcinolone doses.

Risk factors for high-risk proliferative diabetic retinopathy and severe visual loss: Early Treatment Diabetic Retinopathy Study Report #18.

Abstract: PURPOSE To identify risk factors for the development of high-risk proliferative diabetic retinopathy (PDR) and for the development of severe visual loss or vitrectomy (SVLV) in eyes assigned to deferral of photocoagulation in the Early Treatment Diabetic Retinopathy Study (ETDRS) METHODS Multivariable Cox models were constructed to evaluate the strength and statistical significance of baseline risk factors for development of high-risk PDR and of SVLV RESULTS The baseline characteristics identified as risk factors for high-risk PDR were increased severity of retinopathy, decreased visual acuity (or increased extent of macular edema), higher glycosylated hemoglobin, history of diabetic neuropathy, lower hematocrit, elevated triglycerides, lower serum albumin, and, in persons with mild to moderate nonproliferative retinopathy, younger age (or type 1 diabetes) The predominant risk factor for development of SVLV was the prior development of high-risk PDR The only other clearly significant factor was decreased visual acuity at baseline In the eyes that developed SVLV before high-risk proliferative retinopathy was observed, baseline risk factors were decreased visual acuity (or increased extent of macular edema), older age (or type 2 diabetes), and female gender CONCLUSIONS These analyses supported the view that the retinopathy-inhibiting effect of better glycemic control extends across all ages, both diabetes types, and all stages of retinopathy up to and including the severe nonproliferative and early proliferative stages and the possibility that reducing elevated blood lipids and treating anemia slow the progression of retinopathy

Azithromycin for the secondary prevention of coronary heart disease events: the WIZARD study: a randomized controlled trial.

Abstract: ContextSeveral lines of evidence have implied an association between Chlamydia pneumoniae infection and atherogenesis.ObjectiveTo determine the effect of 12 weeks of antibiotic therapy on coronary heart disease events in patients with stable coronary artery disease and known C pneumoniae exposure.Design, Setting, and ParticipantsRandomized, placebo-controlled trial of 7747 adults with previous myocardial infarction that had occurred at least 6 weeks previously (median, 2.6 years) and a C pneumoniae IgG titer of 1:16 or more. Patients were recruited from 271 clinical practices in North America, Europe, Argentina, and India, from October 10, 1997, to July 22, 2001.InterventionThe patients received either azithromycin (600 mg/d for 3 days during week 1, then 600 mg/wk during weeks 2-12; n = 3879) or placebo (n = 3868).Main Outcome MeasuresThe primary event was the first occurrence of death from any cause, nonfatal reinfarction, coronary revascularization, or hospitalization for angina. Patients were followed up until 1038 events accrued.ResultsAfter a median of 14 months of follow-up, there was no significant risk reduction in the likelihood of a primary event with azithromycin vs placebo (7% [95% confidence interval, −5% to 17%], P = .23). Analysis of hazard ratios suggested early benefits of azithromycin on the primary event and on death or reinfarction, but these decreased over time. There were no significant risk reductions for any of the components of the primary end point including death (8%), recurrent myocardial infarction (7%), revascularization procedures (5%), or hospitalizations for angina (−1%). Adverse events related to study drug were reported by 13.2% of those randomized to receive azithromycin, predominantly a result of diarrhea, compared with 4.6% randomized to receive placebo, and resulted in discontinuation of drug in 1.6% of those taking azithromycin and 0.4% taking placebo.ConclusionAmong stable patients with previous myocardial infarction and with evidence of C pneumoniae exposure, a 3-month course of azithromycin did not significantly reduce the clinical sequelae of coronary heart disease.

A Diet History Questionnaire Ranks Nutrient Intakes in Middle-Aged and Older Men and Women Similarly to Multiple Food Records

Abstract: We evaluated the reproducibility of a modified version of the National Cancer Institute diet history questionnaire and also studied comparability of nutrient estimates from this questionnaire to those from four 2-d food records. Subjects (n = 211) were from a population-based sample of middle-aged and older adults participating in the Beaver Dam Eye Study in south-central Wisconsin. Median age-specific correlation coefficients between the questionnaire, administered twice at a 3-mo interval, were 0.8 in men and 0.7 in women (range = 0.5 to 0.9). Questionnaire estimates of protein, cholesterol, thiamin, niacin, iron and zinc were consistently lower than food record estimates whereas estimates of fat were higher. Correlation coefficients between estimates from the questionnaire and records were generally > 0.5, indicating overall good agreement in ranking. However, the range in correlation coefficients was wide [ranging from 0.06 for iron (without supplements) in middle-aged women to 0.8 for alcohol in middle-aged men and women]. Questionnaire estimates similarly classified persons into the lowest two food record quintiles of intake 50 to 93% of the time depending on nutrient. These results suggest that the questionnaire produces nutrient estimates that rank individuals on the basis of intake of most nutrients similarly to estimates from multiple food records.

Out of the Crisis

Abstract: According to W. Edwards Deming, American companies require nothing less than a transformation of management style and of governmental relations with industry. In Out of the Crisis, originally published in 1982, Deming offers a theory of management based on his famous 14 Points for Management. Management's failure to plan for the future, he claims, brings about loss of market, which brings about loss of jobs. Management must be judged not only by the quarterly dividend, but by innovative plans to stay in business, protect investment, ensure future dividends, and provide more jobs through improved product and service. In simple, direct language, he explains the principles of management transformation and how to apply them.

Inflammation, Atherosclerosis, and Coronary Artery Disease

Abstract: ecent research has shown that inflammation plays a key role in coronary artery disease (CAD) and other manifestations of atherosclerosis. Immune cells dominate early atherosclerotic lesions, their effector molecules accelerate progression of the lesions, and activation of inflammation can elicit acute coronary syndromes. This review highlights the role of inflammation in the pathogenesis of atherosclerotic CAD. It will recount the evidence that atherosclerosis, the main cause of CAD, is an inflammatory disease in which immune mechanisms interact with metabolic risk factors to initiate, propagate, and activate lesions in the arterial tree. A decade ago, the treatment of hypercholesterolemia and hypertension was expected to eliminate CAD by the end of the 20th century. Lately, however, that optimistic prediction has needed revision. Cardiovascular diseases are expected to be the main cause of death globally within the next 15 years owing to a rapidly increasing prevalence in developing countries and eastern Europe and the rising incidence of obesity and diabetes in the Western world. 1 Cardiovascular diseases cause 38 percent of all deaths in North America and are the most common cause of death in European men under 65 years of age and the second most common cause in women. These facts force us to revisit cardiovascular disease and consider new strategies for prediction, prevention, and treatment.

Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association

Abstract: The aim of this updated guideline is to provide comprehensive and timely evidence-based recommendations on the prevention of future stroke among survivors of ischemic stroke or transient ischemic attack. The guideline is addressed to all clinicians who manage secondary prevention for these patients. Evidence-based recommendations are provided for control of risk factors, intervention for vascular obstruction, antithrombotic therapy for cardioembolism, and antiplatelet therapy for noncardioembolic stroke. Recommendations are also provided for the prevention of recurrent stroke in a variety of specific circumstances, including aortic arch atherosclerosis, arterial dissection, patent foramen ovale, hyperhomocysteinemia, hypercoagulable states, antiphospholipid antibody syndrome, sickle cell disease, cerebral venous sinus thrombosis, and pregnancy. Special sections address use of antithrombotic and anticoagulation therapy after an intracranial hemorrhage and implementation of guidelines.

Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease

Abstract: Metabolomics studies hold promise for the discovery of pathways linked to disease processes. Cardiovascular disease (CVD) represents the leading cause of death and morbidity worldwide. Here we used a metabolomics approach to generate unbiased small-molecule metabolic profiles in plasma that predict risk for CVD. Three metabolites of the dietary lipid phosphatidylcholine—choline, trimethylamine N-oxide (TMAO) and betaine—were identified and then shown to predict risk for CVD in an independent large clinical cohort. Dietary supplementation of mice with choline, TMAO or betaine promoted upregulation of multiple macrophage scavenger receptors linked to atherosclerosis, and supplementation with choline or TMAO promoted atherosclerosis. Studies using germ-free mice confirmed a critical role for dietary choline and gut flora in TMAO production, augmented macrophage cholesterol accumulation and foam cell formation. Suppression of intestinal microflora in atherosclerosis-prone mice inhibited dietary-choline-enhanced atherosclerosis. Genetic variations controlling expression of flavin monooxygenases, an enzymatic source of TMAO, segregated with atherosclerosis in hyperlipidaemic mice. Discovery of a relationship between gut-flora-dependent metabolism of dietary phosphatidylcholine and CVD pathogenesis provides opportunities for the development of new diagnostic tests and therapeutic approaches for atherosclerotic heart disease.