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The most part, this experience has been in Hodgkin's disease. To date, complete responses have not been achieved reviewed in Ref. 292 ; . Because donor CTLs may be alloreactive, potential hazards of adoptive immunotherapy include graft-versus-host disease. In addition, tumor resistance may occur because of mutations in EBV epitopes recognized by CTLs or by other mechanisms e.g., production of cytokines such as IL-10 ; exploited by the tumor to evade surveillance 299 ; . Efforts are also underway to develop an EBV vaccine either to protect against initial infection or to boost immunity in individuals with EBV-related tumors. The vaccines currently under investigation are using combinations of several defined EBV epitopes to induce EBV-specific CTL immunity 293 ; . Finally, there is the possibility of using gene therapy vaccine vectors in which numerous, linearly joined EBV-specific epitope sequences are expressed as polypeptides and presented for CTL recognition and induction of EBV-specific CTL immunity 294 ; . Monoclonal Antibodies. The anti-CD20 monoclonal antibody designated Rituximab has enjoyed significant success in the treatment of a variety of CD20-expressing lymphomas. It is also an effective agent in the management of EBV-related lymphoproliferative disorders. A response rate of 69% mostly complete responses ; has been reported in a group of transplant recipients either solid organ or hematopoietic stem cell transplant; Ref. 298 ; . Because these lymphomas use IL-6 as a growth factor, anti-IL-6 monoclonal antibodies have also been tried. The reported response rate was 67% 8 of 12 patients treated; Ref. 299 ; . In summary, therapy for EBV-associated tumors remains largely in the nascent stages, but research is being fueled by the successful development of new antiviral and immunological approaches. To date, antiviral agents have received only perfunctory consideration, perhaps because of uncertainty regarding the role of EBV in maintaining established cancers. However, recent studies suggest that selected antiviral compounds, as well as therapeutic strategies such as use of adoptive immunotherapy with EBV-specific CTLs or administration of targeted monoclonal antibodies, hold considerable promise for the treatment of EBV-related malignancies, for example, voltaren 25 mg.
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Is shown in Figs. 2A, 2B and 2C, respectively. In non-tumor tissues, strong signals were observed only in the lymph follicles Fig. 2D ; . The intensity of lymphoid follicles was 2 moderate ; . The intensity and extent % positive area ; of COX-2 staining in each cancer grade are summarized in Table 2. In order to investigate the relationship between COX-2 expression and cancer grade, the COX-2 scores were next evaluated in the bladder tumor specimens Fig. 3 ; . The mean value of the COX-2 score in each grade was as follows: grade 1, 3.25 1.96; grade 2, 4.41 1.58; and grade 3, 4.93 1.97. The score was higher in the high grade cases with a significant difference between grades 1 and 2 p 0.05 ; and grades 1 and 3 p 0.01 ; . Additionally, we evaluated the relationship between COX-2 expression and tumor stage Fig. 4 ; . The mean value of the COX-2 score in low and high stage was 1.65 0.13 and 2.24 0.20, respectively. The.
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14. Treanor JJ, Campbell JD, Zangwill KM, Rowe T, Wolff M. Safety and immunogenicity of an inactivated subvirion influenza A H5N1 ; vaccine. N Engl J Med 2006; 354: 1343-51. Department of Health. Development and production. 2007a. Available at: : dh.gov PandemicFlu Vaccination Vaccinatio nArticle fs en?CONTENT ID 4135536&chk hfC8RC. Last accessed: Feb. 2007. 16. Bender BS, Croghan T, Zhang L, Small PA, Jr. Transgenic mice lacking class I major histocompatibility complexrestricted T cells have delayed viral clearance and increased mortality after influenza virus challenge. J Exp Med 1992; 175: 1143-5. Lawrence CW, Ream RM, Braciale TJ. Frequency, specificity, and sites of expansion of CD8 + T cells during primary pulmonary influenza virus infection. J Immunol 2005; 174: 5332-40. Woodland DL. Cell-mediated immunity to respiratory virus.
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1. Ikekawa T, Nakanishi M, Uehara N, Chihara G, Fukuoka F. Antitumor action of some basidiomycetes, especially Phellinus linteus. Jpn J Cancer Res Gann ; 1968; 59: 1557. Sasaki T, Arai Y, Ikekawa T, Chihara G, Fukuoka F. Antitumor polysaccharides from some polyporaceae, Ganoderma applanatum Pers. ; Pat and Phellinus linteus Berk. Et Curt ; Aoshima. Chem Pharm Bull 1971; 19: 8216. Han SB, Lee CW, Jeon YJ, Hong ND, Yoo ID, Yang KH, et al. The inhibitory effect of polysaccharides isolated from Phellinus linteus on tumor growth and metastasis. Immunopharmacol 1999; 41: 15764. Nakamura T, Matsugo S, Uzuka Y, Matsuo S, Kawagishi H. Fractionation and anti-tumor activity of the mycelia of liquid-cultured Phellinus linteus. Biosci Biotechnol Biochem 2004; 68: 86872. Song KS, Cho SM, Lee JH, Kim HM, Han SB, Ko KS, et al. B-lymphocyte-stimulating polysaccharide from mushroom Phellinus linteus. Chem Pharm Bull 1995; 43: 21058. Kim HM, Han SB, Oh GT, Kim YH, Hong DH, Hong ND, et al. Stimulation of humoral and cell mediated immunity by polysaccharide from mushroom Phellinus linteus. Int J Immunopharmacol 1996; 18: 295303. Kim GY, Oh YH, Park YM. Acidic polysaccharide isolated from Phellinus linteus induces nitric oxide-mediated tumoricidal activity of macrophages through protein tyrosine kinase and protein kinase C. Biochem Biophys Res Commun 2003; 309: 399407. Park SK, Kim GY, Lim JY, Kwak JY, Bae YS, Lee JD, et al. Acidic polysaccharides isolated from Phellinus linteus induce phenotypic and functional maturation of murine dendritic cells. Biochem Biophys Res Commun 2003; 3012: 44958. Li G, Kim DH, Kim TD, Park BJ, Park HD, Park JI, et al. Protein-bound polysaccharide from Phellinus linteus induces G2 M phase arrest and apoptosis in SW480 human colon cancer cells. Cancer Lett 2004; 216: 17581 and exelon and voltaren, for instance, voltaren wirkstoff.
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Cyclosporin products competing with Neoral have entered the transplantation market segment in the US, Germany and elsewhere. We have filed patent infringement actions against manufacturers of these generic products. However, despite a finding of infringement and an award of damages against one of these manufacturers in the US, we have so far not succeeded in obtaining an injunction, or a final judgment of damages against any of the manufacturers we have sued. Aredia. Our patent protection for Aredia is limited. Generic versions of Aredia were launched in the US in 2001 and 2002. Generic products in competition with Aredia are on sale in Canada and elsewhere. However, in 2002, we launched Zometa, our more potent successor product to Aredia. Sandostatin. Basic patent protection for Sandostatin has expired in the US and Japan and will expire April 2003 in Germany and the UK, 2006 in France, and 2007 in Italy. However, protection extending to 2010 2013 and beyond in the US ; continues in major markets for Sandostatin LAR, which represents a substantial and growing proportion of our octreotide sales. Cibacen Lotensin Cibadrex. The basic benazepril substance patent for Cibacen Lotensin Cibadrex expired in Japan in 2002 and will expire in the US in August 2003 or expected to expire in February 2004 with any six-month pediatric exclusivity ; and in 2004-08 in major markets in the EU. However, Lotrel, which is a combination of benazepril with amlodipine, is patented in the US until 2017. Lamisil. Lamisil is covered generically by a patent family which will expire in 2004 in the US, March 2003 in Japan and has expired in other major countries. Another patent family covers the product specifically and expires in 2006 in the US, 2004-05 in Japan and 2005-07 in major EU countries. The specific US patent is being challenged by Dr. Reddy Laboratories in the US. Voltaren. Voltaten is off-patent. As a result, revenue from Voltaeen may decline significantly over the next few years. The loss of patent protection can have a significant impact on our Pharmaceuticals Division. We work to offset these negative effects by developing and patenting inventions that result in process and product enhancements and by positioning many of our products in specific market niches. However, there can be no assurance that this strategy will be effective in the future to extend competitive advantage, or that we will be able to avoid substantial adverse effects from future patent expirations. CONSUMER HEALTH The business of our Consumer Health Division is conducted by a number of affiliated companies throughout the world. In 2002, the Consumer Health Division was reorganized to include our Generics, OTC self-medication, Animal Health, Medical Nutrition including our Nutrition & Sant unit ; , Infant & e Baby, and our CIBA Vision Business Units. Each Business Unit has a leading market position in its segment by producing and marketing high quality health-related products. In 2002, the affiliates of the Consumer Health Division employed 27, 552 associates and had CHF 11.4 billion in sales, which represented 35% of the Group's sales. In February 2002, we announced our intention to divest our Health and Functional Food business before the end of 2002. This was intended to better meet customer needs and strengthen growth initiatives, furthering our strategic focus on healthcare with pharmaceuticals at the core. In November 2002, we completed the divestment of our Food & Beverage business, including Ovaltine Ovomaltine , Caotina and Lacovo , to Associated British Foods plc for EUR 272.5 million approximately CHF 402 million ; . In November 2002, we also announced that we were delaying the divestment of the remainder of the Health and Functional Food business due to a lack of attractive offers. These remaining Health and Functional Food businesses--the Health Food & Slimming and Sports Nutrition lines--have been reorganized into a stand-alone unit called Nutrition & Sant. For reporting e purposes, Nutrition & Sant's results will be included in the results of the Medical Nutrition Business e Unit. We have announced our intention to sell Nutrition & Sant once an attractive bid is received. e 39 and floxin.
| Effects of voltarenSource of operating revenue for most retail pharmacies. ; State Officials also report that prices from First DataBank are selfreported and often lag significantly behind the market. Emerging strategies for obtaining crucial price information Table 3 ; include making reimbursement concessions to pharmacies in exchange for pricing information, seeking pricing information from alternative sources including State-run hospitals or clinics ; , and implementing formal policies requiring price disclosure. Pharmacies might also be more willing to share pricing information with State Medicaid Programs under alternate reimbursement schemes that would reduce their dependency on profits from generic drug sales. Pharmacists are now actively calling for reimbursement based on services provided rather than on prescriptions dispensed, i.e., direct payment for helping physicians optimize drug choice and dosing and for helping recipients optimize drug regimen adherence. Besides reducing pharmacists' economic dependency on the spread between wholesaler purchase price and retail sale price, thus removing a source of antagonism between pharmacists and State Medicaid officials that currently impedes information sharing, such a reimbursement paradigm would reduce pharmacists' financial incentive to dispense more drugs. One would expect this realignment of economic incentives to help contain costs by reducing drug utilization. A final consideration surrounding the proliferation and development of MAC programs is the question of whether aggres.
Stroke, aspirin has been shown to significantly reduce the risk of the combined endpoint of stroke or death and the combined endpoint of TIA, stroke, or death by about 1318 percent. Suspect Acute Myocardial Infarction MI ; : In large, multi-center study of aspirin, streptokinase, and the combination of aspirin and streptokinase in 17, 187 patients with suspected acute MI, aspirin treatment produced a 23-percent reduction in the risk of vascular mortality. Aspirin was also shown to have an additional benefit in patients given a thrombolytic agent. Prevention of Recurrent MI and Unstable Angina Pectoris: These indications are supported by the results of six large, randomized, multicenter, placebo-controlled trials of predominantly male post-MI subjects and one randomized placebo-controlled study of men with unstable angina pectoris. Aspirin therapy in MI subjects was associated with a significant reduction about 20 percent ; in the risk of the combination endpoint of subsequent death and or nonfatal reinfarction in these patients. In aspirin-treated unstable angina patients the event rate was reduced to 5 percent from the 10 percent rate in the placebo group. Chronic Stable Angina Pectoris: In a randomized, multi-center, double-blind trial designed to assess the role of aspirin for prevention of MI in patients with chronic stable angina pectoris, aspirin significantly reduced the primary combined endpoint of nonfatal MI, fatal MI, and sudden death by 34 percent. The secondary endpoint for vascular events first occurrence of MI, stroke, or vascular death ; was also significantly reduced 32 percent ; . Revascularization Procedures: Most patients who undergo coronary artery revascularization procedures have already had symptomatic coronary artery disease for which aspirin is indicated. Similarly, patients with lesions of the carotid bifurcation sufficient to require carotid endarterectomy are likely to have had a precedent event. Aspirin is recommended for patients who undergo revascularization procedures if there is a preexisting condition for which aspirin is already indicated. Rheumatologic Diseases: In clinical studies in patients with rheumatoid arthritis, juvenile rheumatoid arthritis, ankylosing spondylitis and osteoarthritis, aspirin has been shown to be effective in controlling various indices of clinical disease activity. ANIMAL TOXICOLOGY The acute oral 50 percent lethal dose in rats is about 1.5 g kg and in mice 1.1 g kg. Renal papillary necrosis and decreased urinary concentrating ability occur in rodents chronically administered high doses. Dose-dependent gastric mucosal injury occurs in rats and humans. Mammals may develop aspirin toxicosis associated with GI symptoms, circulatory effects, and central nervous system depression. See Overdosage.
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The demographic characteristics of patients with chronic heart failure have mostly been obtained from community-based epidemiological studies and large, multicentre intervention trials.2 However, compared with participants of intervention trials, populations in community-based studies are generally older, less predominantly male, more likely to have comorbidities, and presentation with diastolic failure is common3 tables 1 and 2 ; .455 Ethnic origin Hypertension is a major aetiological factor for subsequent chronic heart failure in African-American patients. These patients are generally thought to respond less well than white patients to inhibitors of angiotensinconverting enzyme ACE ; for treatment of hypertension, 56 perhaps owing to their overall low renin status. Such observations have, however, been challenged by the findings of the recent AASK trial57 see panel for explanation of trial acronyms ; . In the setting of established chronic heart failure, the responsiveness to ACE inhibitors and blockers ; has also been assessed.
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I. Causes A. Failed communication 1. Poorly handwritten or verbal orders 2. Drugs with similar-sounding or similar-looking names 3. Misuse of zeros in decimal numbers 4. Use of apothecary measures grains, drams ; on 5. Use of package units amps, vials, tablets ; instead of metric measures grams, milligrams, milliequivalents ; 6. Misinterpreted abbreviations 7. Ambiguous or incomplete orders B. Poor distribution practices C. Dose miscalculations D. Drug packaging and drug delivery systems E. Incorrect drug administration F Lack of patient education . II. Prevention Strategies A. Professional responsibilities include 1. Clarify any orders that are not obviously and clearly legible. 2. Clarify the dosage and ask the prescriber to write out the word "units." 3. Clarify any abbreviated drug name or the abbreviated dosing frequencies. 4. Do not accept dosages expressed in package units or volume instead of metric weight. 5. Suspect a missed decimal point and clarify any order if the dose requires more than three dosing units. 6. If dose ordered requires use of multiple dosage units or very small fractions of a dose unit, review the dosage, have another health-care provider.
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