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If, after you have increased the medication, you find that the previous -- that is, lower-dose was just as effective, it would be better to use the lower dose. 1 U.S. Department of Health, Education, and Welfare. Smoking and Health: Report of the Advisory Committee to the Surgeon General of the Public Health Service. Washington: U.S. Department of Health, Education, and Welfare, Public Health Service, Center for Disease Control; 1964. 2 Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health. The Health Consequences of Smoking: A Report of the Surgeon General. Washington D.C.: U.S. Government Publishing Office; 2004. 3 National Cancer Institute. Changes in Cigarette-Related Disease Risks and Their Implication for Prevention and Control. Bethesda, MD: U.S. Department of Health and Human Services; 1997. 4 U.S. Environmental Protection Agency. Respiratory Health Effects of Passive Smoking: Lung Cancer and Other Disorders. Washington: Environmental Protection Agency, Office of Research and Development, Office of Air and Radiation; 1992. 5 Institute of Medicine. Clearing the Smoke: Assessing the Science Base for Tobacco Harm Reduction. Washington: National Academy Press; 2001. 6 International Agency for Research on Cancer. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: Tobacco Smoke and Involuntary Smoking. Vol 83. Lyon: International Agency for Research on Cancer; 2002. 7 Fiore MC, Bailey WC, Cohen SJ, et al. Treating Tobacco Use and Dependence. Clinical Practice Guideline. Rockville: U.S. Department of Health and Human Services, Public Health Service; 2000. 8 US Public Health Service. A clinical practice guideline for treating tobacco use and dependence: a US Public Health Service report. The Tobacco Use and Dependence Clinical Practice Guideline Panel, Staff, and Consortium Representatives. JAMA. 2000; 283: 3244-3254. Cokkinides VE, Ward E, Jemal A, Thun MJ. Under-use of smokingcessation treatments: results from the National Health Interview Survey, 2000. J Prev Med. 2005; 28: 119-122. Centers for Disease Control and Prevention. Annual smokingattributable mortality, years of potential life lost, and economic costsUnited States, 1995-1999. MMWR. 2002; 51: 300-303. Centers for Disease Control and Prevention. Cigarette smokingattributable morbidityUnited States, 2000. MMWR. 2003; 52: 842844. Centers for Disease Control and Prevention. Cigarette smoking among adultsUnited States, 2001. MMWR. 2003; 52: 953-956. Kandel D, Wu P. The contributions of mothers and fathers to the intergenerational transmission of cigarette smoking in adolescence. J Res Adolescence. 1995; 5: 225-252. Orth SR. Effects of smoking on systemic and intrarenal hemodynamics: influence on renal function. J Soc Nephrol. 2004; 15: S58-S63. 15 U.S. Department of Health and Human Services. Health Benefits of Smoking Cessation. A Report of the US Surgeon General. Rockville, MD: U.S. Department of Health and Human Services; 1990. 16 Doll R, Peto R, Boreham J, Sutherland I. Mortality in relation to smoking: 50 years' observations on male British doctors. BMJ. 2004; 328: 1519. Critchley J, Capewell S. Smoking cessation for the secondary prevention of coronary heart disease. Cochrane Database Syst Rev. 2004 1 ; : CD003041. 18 Critchley JA, Capewell S. Mortality risk reduction associated with smoking cessation in patients with coronary heart disease: a systematic review. JAMA. 2003; 290: 86-97. Wilson K, Gibson N, Willan A, Cook D. Effect of smoking cessation on mortality after myocardial infarction. Arch Intern Med. 2000; 160: 939-944. Wannamethee SG, Shaper AG, Whincup PH, Walker M. Smoking cessation and the risk of stroke in middle-aged men. JAMA. 1995; 274: 155-160. Scanlon PD, Connett JE, Waller LA, et al. Smoking cessation and lung function in mild-to-moderate chronic obstructive pulmonary disease. J Resp Crit Care Med. 2000; 161: 381-390. Giovino GA, Henningfield JE, Tomar SL, Escobedo LG, Slade J. Epidemiology of tobacco use and dependence. Epidemiol Rev. 1995; 17: 48-65. Hughes JR. Motivating and helping smokers to stop smoking. J Gen Intern Med. 2003; 18: 1053-1057. DiClemente C, Prochaska J, Fairhurst S, Velicer W, Elesquez M, Rossi J. The process of smoking cessation: an analysis of precontemplation, contemplation, and preparation stages of change. J Consult Clin Psychol. 1991; 59: 295-304. Velicer WF, Hughes SL, Fava JL, Prochaska JO, DiClemente CC. An empirical typology of subjects within stage of change. Addict Behav. 1995; 20: 299-320. Goldberg D, Hoffman A, Anel D. Understanding people who smoke and how they change: a foundation for smoking cessation in primary care, part 1. Dis Mon. 2002; 48: 385-439. Goldberg D, Hoffman A, Anel D. Understanding people who smoke and how they change: a foundation for smoking cessation in primary care, part 2. Dis Mon. 2002; 48: 445-485. Dijkstra A, DeVries H. Subtypes of precontemplating smokers defined by different long-term plans to change their smoking behavior. Health Educ Res. 2000; 15: 423-434. Katz DA, Muehlenbruch DR, Brown RB, Fiore MC, Baker TB, AHRQ Smoking Cessation Guideline Study Group. Effectiveness of a clinic-based strategy for implementing the AHRQ Smoking Cessation Guideline in primary care. Prev Med. 2002; 35: 293-301. Kenford SL, Fiore MC. Promoting tobacco cessation and relapse prevention. Med Clin North Am. 2004; 88: 1553-1574, xi-xii. 31 Park EW, Tudiver F, Schultz JK, Campbell T. Does enhancing partner support and interaction improve smoking cessation? A meta-analysis. Ann Fam Med. 2004; 2: 170-174. Lumley J, Oliver SS, Chamberlain C, Oakley L. Interventions for promoting smoking cessation during pregnancy. Cochrane Database Syst Rev. 2004; 3 CD001055 pub 2 ; . 33 Windsor R, Oncken C, Henningfield J, Hartmann K, Edwards N. Behavioral and pharmacological treatment methods for pregnant smokers: issues for clinical practice. J Med Womens Assoc. 2000; 55: 304-310. Nerve cells communicate with each other using chemicals called neurotransmitters. Parkinson disease is a neurological nerve ; disorder which destroys certain cells in the brain, resulting in a shortage of a neurotransmitter called dopamine. The affected nerves in Parkinson disease patients are located in the area of the brain which controls movement. The first signs of Parkinson disease can be quite subtle, from softer, slower speech to an arm that doesn't swing when you walk. The most common, most noticeable symptom is generally tremors or shaking ; beginning on one side of the body, usually in one hand. As the disease progresses, the tremors may become worse, moving up the arm and into the head, lips, or feet. Later, bradykinesia or slowed motion ; can cause problems throughout the body, from a shuffling walk, to difficulty performing routine tasks. Muscles can become stiff, speech can become soft and slow, and in later stages even swallowing can be difficult. In some rare and severe cases, reason and memory may start to decline as a result of a mental condition called dementia. Parkinson disease is progressive, meaning the symptoms get worse overtime, but in many of the 1.5 million sufferers it progresses slowly for years. Further, treatments which replace the missing neurotransmitter have proven to be quite effective, other valuable treatments have been and are currently being developed.
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The pharmaceutical industry is highly competitive. Our principal pharmaceutical competitors consist of major international companies, many of which are larger and have greater financial resources, technical staff, manufacturing, research and development and marketing capabilities than Elan. Other competitors consist of smaller research companies and generic drug manufacturers. A drug may be subject to competition from alternative therapies during the period of patent protection or regulatory exclusivity and, thereafter, it may be subject to further competition from generic products. Additionally, generic competitors can challenge existing patent protection or regulatory exclusivity. Generic competitors do not have to bear the same level of research and development and other expenses associated with bringing a new branded product to market. As a result, they can charge much less for a competing version of our product. Managed care organisations typically favour generics over brand name drugs, and governments encourage, or under some circumstances mandate, the use of generic products, thereby reducing the sales of branded products that are no longer patent protected. Governmental and other pressures toward the dispensing of generic products may rapidly and significantly reduce, or slow the growth in, the sales and profitability of certain of our products not protected by patents or regulatory exclusivity and may adversely affect our future results and financial condition. For example, generic forms of Ceclor CD and Myambutol were approved by the FDA and launched in 2001, significantly reducing the revenues and profitability of these products. Generic forms of Zanaflex were launched in 2002. As a result, product revenue from Zanaflex declined from .7 million in the first quarter of 2002 to ##TEXT##.8 million in the first quarter of 2003. Additionally, competitor products, including generic competitors' products, to any of Elan's other products may become available. The launch of generic versions of Elan's products may materially adversely affect our business, financial condition and results of operations. Our competitive position depends, in part, upon our continuing ability to discover, acquire and develop innovative, cost-effective new products, as well as new indications and product improvements protected by patents and other intellectual property rights. We also compete on the basis of price and product differentiation and through our sales and marketing organisation that provides information to medical professionals and launches new products. If we fail to maintain our competitive position, our business, financial condition and results of operations may be materially adversely affected. And because these zanaflex substitutes are not fda approved, the herbal muscle spasm remedy marketers can claim just about anything that they want to and get away with it.

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[31] Saggerson E, Carpenter C, Cheng C, Sooroanna S. Subcellular distribution and some properties of N-ethylmaleimide-sensitive and-insensitive forms of glycerol phosphate acyltransferase in rat adipocytes. Biochem J 1980; 190: 1839. [32] Yamashita S, Numa S. Partial purification and properties of glycerophosphate acyltransferase from rat liver. Formation of 1-acylglycerol 3-phosphate from sn-glycerol 3-phosphate and palmityl coenzyme A Eur J Biochem 1972; 31: 56573. [33] Mishra S, Kamisaka Y. Purification and characterization of thiol-reagent-sensitive glycerol-3-phosphate acyltransferase from the membrane fraction of an oleaginous fungus. Biochem J 2001; 355: 31522. [34] Coleman RA, Bell RM. Selective changes in enzymes of the sn-glycerol-3-phosphate and dihydroxyacetonephosphate pathways of triacylglycerol biosynthesis during differentiation of 3T3-L1 pre-adipocytes. J Biol Chem 1980; 255: 76817. [35] Coleman RA, Haynes EB. Selective changes in microsomal enzymes of triacylglycerol and phosphatidylcholine synthesis in fetal and postnatal rat liver: Induction of microsomal sn-glycerol 3-P and dihydroxyacetone-P acyltransferase activities. J Biol Chem 1983; 258: 45065. [36] Hammond LE, Gallagher PA, Wang S, Posey-Marcos E, Hiller S, Kluckman K, et al. Mitochondrial glycerol-3phosphate acyltransferase deficient mice have reduced hepatic triacylglycerol content, decreased VLDL, and altered fatty acid composition. Mol Cell Biol 2002; 22: 820414. [37] Lau TE, Rodriguez MA. A protein tyrosine kinase associated with the ATP-dependent inactivation of adipose diacylglycerol acyltransferase. Lipids 1996; 31: 27783. [38] Farese RV, Standaert ml, Yamada K, Huang LC, Zhang C, Cooper DR, et al. Insulin-induced activation of glycerol-3-phosphate acyltransferase by a chiro-inositol-containing insulin mediator is defective in adipocytes of insulin-resistant, type II diabetic, Goto-Kakizaki rats. Proc Natl Acad Sci USA 1994; 91: 110404. [39] Vila MC, Farese RV. Insulin rapidly increases glycerol-3-phosphate acyltransferase activity in rat adipocytes. Arch Biochem Biophys 1991; 284: 3668. [40] Yamada K, Standaert ml, Yu B, Mischak H, Cooper DR, Farese RV. Insulin-like effects of sodium orthovanadate on diacylglycerol-protein kinase C signaling in BC3H-1 myocytes. Arch Biochem Biophys 1994; 312: 16772. [41] Vila MC, Milligan G, Standaert ml, Farese RV. Insulin activates glycerol-3-phosphate acyltransferase de novo phosphatidic acid synthesis ; through a phospholipid-derived mediator. Apparent involvement of Gi and activation of phospholipase C Biochemistry 1990; 29: 873540. [42] Monroy G, Rola FH, Pullman ME. A substrate and position-specific acylation of sn-glycerol 3-phosphate by rat liver mitochondria. J Biol Chem 1972; 247: 688494. [43] Bremer J, Bjerve KS, Borrebaek B, Christiansen R. The glycerolphosphate acyltransferases and their function in the metabolism of fatty acids. Mol Cell Biochem 1976; 12: 11325. [44] Monroy G, Kelker HC, Pullman ME. Partial purification and properties of an acyl coenzyme A: sn-glycerol 3-phosphate acyltransferase from rat liver mitochondria. J Biol Chem 1973; 248: 284552. [45] Haldar D, Tso W-W, Pullman ME. The acylation of sn-glycerol 3-phosphate in mammalian organs and Ehrlich ascites tumor cells. J Biol Chem 1979; 254: 45029. [46] Vancura A, Haldar D. Purification and characterization of glycerophosphate acyltransferase from rat liver mitochondria. J Biol Chem 1994; 269: 2720915. [47] Vancura A, Carroll MA, Haldar D. A lysophosphatidic acid-binding cytosolic protein stimulates mitochondrial glycerophosphate acyltransferase. Biochem Biophys Res Commun 1991; 175: 33943. [48] Vancura A, Haldar D. Regulation of mitochondrial and microsomal phospholipid synthesis by liver fatty acidbinding protein. J Biol Chem 1992; 267: 143539. [49] Martin GG, Danneberg H, Kumar LS, Atshaves BP, Erol E, Bader M, et al. Decreased liver fatty acid binding capacity and altered liver lipid distribution in mice lacking the liver fatty acid-binding protein gene. J Biol Chem 2003; 278: 2142938. [50] Paulauskis JD, Sul HS. Cloning and expression of mouse fatty acid synthase and other specific mRNAs: developmental and hormonal regulation in 3T3-L1 cells. J Biol Chem 1988; 263: 704954. [51] Shin D-H, Paulauskis JD, Moustaid N, Sul HS. Transcriptional regulation of p90 with sequence homology to Escherichia coli glycerol-3-phosphate acyltransferase. J Biol Chem 1991; 266: 238349. 100 Woodbridge Center Drive Phone: 732-726-0441 Suite 202 FAX: 732-726-0951 Woodbridge, NJ 07095 e-mail: info strategicmedical strategicmedical Officers: Jerry Brager, chairman of the board CEO; Donna Weber, president SMC, Denver Andrew Burling, senior v.p. general manager; Bernard Coccia, v.p. management supervisor; Paul Kaiser, v.p., multimedia and Internet services; Marilyn Gartner, v.p. account supervisor. Year founded: 1982.
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