Procrit

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Epogen and procrit are also approved for patients scheduled for major surgery to reduce potential blood transfusions and for the treatment of anemia due to zidovudine therapy in hiv patients, the fda said. Than single. These observations are more in keeping with a luteal than a placental origin. Furthermore, that we observed that the levels of pro- C inhibin in women with a frozenthawed embryo pregnancy are significantly higher than levels previously reported 13, 14 ; reflects that the women in this current study were treated with protocols where there is often luteal function present, whereas in previous reports 13, 14 ; , women receiving frozen-thawed ETs underwent a protocol of complete ovarian suppression and therefore had a total absence of luteal tissue. Because there is an obvious discrimination in pro- C inhibin levels between successful and unsuccessful cycles and because it has been previously shown that administration of exogenous hCG rescues luteal production of pro- C inhibin 7 ; , it is likely that hCG is the physiological stimulus for the higher luteal pro- C inhibin production observed in the successful pregnancies. However, we were unable to confirm an association between circulating pro- C inhibin levels and either progesterone 8 ; or hCG 7 ; at d 1517 in the maternal serum. We did find a weak negative correlation between pro- C inhibin levels and progesterone in the viable frozen ET pregnancies, but because all other correlations were found to be strongly nonsignificant, this may be a type I error and interpretation should be cautious. In addition, we cannot exclude the possibility that a true relationship exists between endogenous progesterone and serum levels of hCG or pro- C inhibin but was affected by the administration of exogenous progesterone. The more convincing experimental design to explore relationships between progesterone and pro- C inhibin would be to undertake interventional studies, such as withholding luteal support and the administration of mifepristone. Clearly, pro- C inhibin is not essential for successful pregnancy because protocols employing complete ovarian suppression causing the absence of luteal tissue are compatible with successful pregnancy 14 ; . However, the fact that an early rise in pro- C levels appears to be a consistent feature specific to clinical pregnancy suggests that it may have a biological role. In this regard, implantation has been previously shown to be optimal at d 8 after fertilization 15 ; . It has also been reported recently that in the week immediately after implantation, an early hCG rise and an abrupt increase in progesterone is associated with fewer pregnancy losses 16 ; . It therefore possible that the progressive rise of pro- C inhibin across this same period 7 ; may reflect the fact that these inhibin forms might also play important roles such as the facilitation of implantation and or decidualization. In support of this possibility are immunohistochemical studies showing that the -subunit staining in the nonpregnant endometrium is weak but becomes strong after decidualization 17 ; . Such speculation should be tempered with some caution because it is presently believed that only the dimeric inhibin.
Introduction: Acute renal failure ARF ; caused by renal ischemia reperfusion I R ; is important clinical problem. Although reperfusion is essential for the survival of ischemic tissue, there is good evidence that reperfusion itself causes additional cellular injury. Reperfusion initiates a complex and interrelated sequence of events that results in injury and the eventual death of renal cells as a result of a combination of both apoptosis and necrosis events. Even though great progress has been made in patient care, there is still high morbidity and mortality associated with ARF. Magnesium is a potent vasodilator whose effects have not been well evaluated in renal ischemia. The aim of this study is evaluate the effect of magnesium supplementation on ischemic ARF and also verify possible alterations of ACE activities specially the 90kDa isoform, a possible genetic marker of hypertension. Methods: Rats were maintained on normal diets supplemented or not with MgCl2.6H2O 1% in drinking water ; during all period of study. On day 25, ischemia was induced by clamping both renal arteries for 30 min followed by 5 days of reperfusion. Four groups were studied: ischemic group WKY-gi and SHR-gi ; , ischemic group with magnesium supplementation WKY-Mg and SHR-Mg ; . Body weight and arterial pressure were measured periodically. We analyzed serum creatinine, blood urea nitrogen and urine ACE activity using Hipuryl-HisLeu HHL ; and Z-Phe-His-Leu ZPhe-HL ; as substrates. One way analysis of variance ANOVA ; was used to calculate the statistical significance between various groups. Statistical significance was set at P 0, 05. Results: We observed a decrease of the body weight and blood pressure soon after surgery in all groups. Measurements of serum creatinine and blood urea nitrogen in ischemic rats with magnesium supplementation were increased at 24, 72 hours and five days after ischemia. ACE activity was increased using ZPHe-HL as substrate when compared to the results obtained with HHL for all studied groups. In SHR ischemic group ACE activity was significantly increased for both substrates at 24 and 72 hours after ischemia when compared to the basal. Using ZPhe-HL as substrate SHR-Mg and WKY-Mg presented values significantly decreased 24 and 72 hours after ischemia compared to SHR-gi and WKY-gi. Conclusion: Our results obtained for WKY and SHR groups suggest that treatment with magnesium decreased ACE activity that could be related to changes in renal tubule decreasing the synthesis and or ACE activity, which attenuates the injury in those animals, protecting them from the lesions possible caused by reperfusion.
The drug company epogen, aranesp, and procrit are all manufactured by amgen, a biotechnology firm with headquarters in thousand oaks, california and locations throughout the united states, canada, europe, asia, and australia.

Table 1. Conditions Related to AF and prohibit. Order procrit Chronic medical conditions in humans. Reviews of Medical Virology 4, 235243. A crucial development in our understanding of G-proteincoupled receptor GPCR ; function has been the identification of the ability of receptors to activate their cognate G-proteins in the absence of an agonist Costa and Herz, 1989 ; . Thus, certain ligands termed inverse agonists and previously characterized as competitive antagonists ; can inhibit agonist-independent receptor activity Costa and Herz, 1989 ; . Subsequent research has identified significant agonist-independent constitutive ; activity at a wide variety of both endogenously and recombinantly expressed GPCRs for review, see Seifert and Wenzel-Seifert, 2002 ; . One of the most powerful tools used by researchers in this area has been the development of GPCRs harboring specific mutations known to enhance the agonist-independent coupling of receptor and G-protein [so-called constitutively active mutant CAM ; receptors] Seifert and Wenzel-Seifert and prolixin.

About procrit epoetin alfa ; procrit is indicated for the treatment of. Description Epoetin alfa EPO ; , e.g., Epogen or Procrit , is a glycoprotein produced by recombinant DNA technology. Recombinant Epoetin has the same biological activity as the endogenous hormone, which induces erythropoiesis by stimulating the division and differentiation of committed erythroid progenitor cells in bone marrow. Endogenous erythropoietin is produced primarily in the kidney. Darbepoetin alfa, Aranesp , is an erythropoiesis stimulating protein closely related to erythropoietin that is produced in Chinese hamster ovary CHO ; cells by recombinant DNA technology. Aranesp has an approximately 3-fold longer terminal half-life than Epoetin alfa when administered by either the IV or SC route and propantheline. A working group of stakeholders to recommend how to make the price review process more transparent. 5.3 Federal Provincial Territorial F P T ; Initiatives At the invitation of federal and provincial ministers of health, the PMPRB has assisted in the work of several committees and task forces studying pharmaceuticals. The PMPRB has recently entered into a Memorandum of Understanding MOU ; with the federal Minister of Health to continue and expand analysis of price trends and cost drivers for F P T public drug plans on behalf of the Working Group on Drug Prices. Under the terms of the MOU, the PMPRB will conduct analyses of the expenditures of public drug plans in Canada including annual price trends, cost-driver studies, comparisons of Canadian and foreign prices of non-patented single-source drugs and inter-provincial drug price comparisons. Auditor General's Report on the PMPRB In 1998, the Auditor General performed a thorough audit of the Board and tabled a report to Parliament on all aspects of its operations. The Board responded positively to the Auditor General's recommendations. Progress has been made on the recommendations and work is ongoing. Workload Pressures Increases From 1992 to 1999, the number of patented drugs under the PMPRB's jurisdiction has increased by 37%, from 791 to 1, 082. In addition to the increased number of patented drugs being reviewed, patentees have become more sophisticated in their approach to the price review process. This has resulted in more creative and complex submissions by patentees in an attempt to justify their prices. These submissions often involve scientific, pharmacoeconomic and jurisdiction issues as seen in the current hearing in the matter of Hoechst Marion Roussel Canada Inc. and the price of Nicoderm.

Essential to protecting the eastern approaches to the Crimea, whereas the Soviets viewed the bridgehead as a launch-point for another possible German offensive into the northern Caucasus. Unlike Stalingrad, Kursk or even Operation Bagration, the campaign is almost unknown in the West, probably due to the fact that there were no real breakthroughs on the ground, no encirclements, no capitulation of German armies. At best, it was a set of limited ground offensives during the boggy months of spring. However, the air battles over the Kuban sector were pivotal to the growth of the VVS as the offensive long-arm of the Red Army, sending a clear message to the Luftwaffe: the VVS was about to return what it had received. In fact, Soviet historians hold this two-month air campaign in early 1943 to be as important to the war effort as the Americans do the battle of Midway. It was a battle fought with such intensity that General K. V. Vershinin, the main Soviet air commander of the sector, claimed on some days he could see an aircraft fall every ten minutes, and it was not unusual for as many as 100 air battles to take place in a day. The German Fourth L u f Air Fleet ; , which included the elite Udet, Molders and Green Hearts JGs Jagdgeschwader, equivalents of Groups ; , was responsible for this area, while its Soviet counterparts were primarily the Fourth and Fifth Air Armies, along with three air corps from STAVKA reserves. Both air forces were roughly equal in size at and propylthiouracil.
Continued from page 13 ; "`A husband found himself in big trouble when he forgot his wedding anniversary. His wife angrily told him, "Tomorrow there better be something for me in the driveway that goes from zero to 180 in five seconds flat." The next morning, the wife found a small package in the driveway. She opened it and found a brand new bathroom scale. Visiting hours for the husband at the hospital are limited due to the extent of the injuries." "A Doctor addressed a large audience in Tampa. The material we put into our stomachs is enough to have killed most of us sitting here, years ago. Red meat is awful. Soft drinks corrode your stomach lining. Chinese food is loaded with MSG. High fat diets can be disastrous, and none of us realizes the long-term harm caused by the germs in our drinking water. But there is one thing that is the most dangerous of all and we all have, or will, eat it. Can anyone here tell me what food it is that causes the most grief and suffering for years after eating it?" After several seconds of quiet, a 75-year-old man in the front row raised his hand, and softly said, "Wedding Cake." "A couple in their nineties are both having problems remembering things. During a checkup, the doctor tells them that they're physically okay, but they might want to start writing things down to help them remember. Later that night, while watching TV, the old man gets up from his chair. "Want anything while I'm in the kitchen?" he asks. "Will you get me a bowl of ice cream?" "Sure." "Don't you think you should write it down so you can remember it?" she asks. "No, I can remember it." "Well, I'd like some strawberries on top, too. Maybe you should write it down, so's not to forget it?" He says, "I can remember that. You want a bowl of ice cream with strawberries." "I'd also like whipped cream. I'm certain you'll forget that, write it down?" she asks. Irritated, he says, "I don't need to write it down, I can remember it! Ice cream with strawberries and whipped cream--I got it, for goodness sake!" Then he toddles into the kitchen. After about 20 minutes, the old man returns from the kitchen and hands his wife a plate of bacon and eggs. She stares at the plate for a moment. "Where's my toast?" "Two women were new arrivals at the pearly gates and were comparing stories on how they died. 1st woman: "I froze to death." 2nd woman: "How horrible!" 1st woman: "It wasn't so bad. After I quit shaking from the cold, I began to get warm and sleepy, and finally died a peaceful death. What about you? 2nd woman: "I died of a massive heart attack. I suspected my husband was cheating, so I came home early to catch him in the act. But instead, I found him all by himself in the den watching TV." 1st woman: "So what happened?" 2nd woman: "I was so sure there was another woman there somewhere that I started running all over the house looking for her. I ran up into the attic and searched, and down into the basement. Then I went through every closet and checked under all the beds. I kept this up until I had looked everywhere, and finally I became so exhausted that I just keeled over with a heart attack and died. 1st woman: "Too bad you didn't look in the freezer. We'd both still be alive!" You can tell who your real nursing friends are when: They remember your special days. They guard your work space. They appear like magic in a room, when needed. They allow you to ventilate. They take the colon prep admit. They buy your kids' whatever fundraiser. They cry with you. They candidly tell you when you've messed up and don't realize it. They actually answer their phone and come in for your "I'm going crazy" call. They go to the laundry and pick up new scrubs for you. They're the last to leave your daughter's wedding reception. They . fill in your own ; "A Minute: They say it takes a minute to find a special person, an hour to appreciate them, a day to love them, but then an entire life to forget them." "Good friends are like stars . You don't always see them, but you know they are always there." e-mail 11 05 ; "At first we see only each other's virtues. Now we are seeing only each other's faults. If we make it through this latter stage then maybe we will see each other and truly be friends." Hugh Prather "Grant me the senility to forget the patients I never liked. The good fortune to run into the patients I do like. And the eyesight to tell the difference!" NURSES calendar ; "A good friend is the person who gives you the better of the two choices, holds your hand when you're scared, helps you fight off those who try to take advantage of you, thinks of you at times when you are not there, reminds you of what you have forgotten, helps you put the past behind you but understands when you need to hold on to it little longer, stays with you so that you have confidence, goes out of their way to make time for you, helps you clear up your mistakes, helps you deal with pressure from others, smiles for you when they are sad, helps you become a better person, and most importantly, loves you!" e-mail, 2005 ; How fortunate you are, when your friend is also a NURSE.

Syringes, needles, or other disposable supplies except those used with insulin ; NOTE: If your plan offers mail service for covered drugs, our mail order pharmacy , Medco Health Solutions, offers excluded drugs at a discount through their home delivery service. For more information, visit medcohealth Prior HFHP authorization The following drugs require proof of medical necessity from the physician requesting HFHP authorization: Anorexiants such as Meridia and Xenical ; . In addition to proof of medical necessity, members must show proof of enrollment in an HFHP-authorized weight loss program. Forteo Fragmin Injectables Zofran Kytril, growth hormone, Epogen, Anzemet, and Procrit ; Lovenox Prevnar Pulmozyme Regranex Retin-A for use other than cosmetic ; Stadol Transdermal Scopolamine patches Tikosyn antiarrhythmic agent ; Zyvox and protopic.

Officials at the U.S. Food and Drug Administration have yet to announce if and when they plan to begin accepting abbreviated applications for follow-on biologics referred to as "biosimilar" drugs in Europe ; , but experts said they do not expect anything from the agency soon. Generic biologic agents can still be approved through a new-drug application NDA ; , but the burden of proof that comes with an NDA undermines some of the cost savings of generic products. "Do you do all your own research . or can FDA look at the file from another company's application? That is the question that is hotly debated, " said Meredith Manning, J.D., a partner with Hogan & Hartson in Washington, D.C. Even innovator companies are stuck with the current system. When Genentech, South San Francisco, Calif., developed a new version of their flagship biologic agent, Procrit epoetin ; , they submitted an NDA rather than the abbreviated application often used for refinements. The generic industry has urged FDA to move forward with developing a non-NDA mechanism for generic biologics, arguing that the science to demonstrate equivalency to existing agents is already available. "Generic [biologics] will become a reality, it is just a matter of how and when, " said Andrea Hofelich, director of media relations for the Generic Pharmaceutical Association. Past statements from FDA officials suggest that they would agree with that assessment. In fact, agency officials had said that they would propose rules for certain biologics, including human growth hormone and insulin, by the end of last year. That did not happen despite both increasing pressure from members of Congress and a lawsuit brought by Sandoz Pharmaceuticals. The company is still waiting for the FDA to act on an application for approval of its growth hormone Omnitrope that they submitted in July 2003. The company's application relied on data produced for the innovator product, Pfizer's Genotropin. The FDA seems to have stepped back under increasing pressure from industry. However, the agency has continued to hold forums in which experts are helping to build the science needed to better assess the properties of biologics. While that has helped define what is needed to show equivalency, it has also made it clear that the agency will need to judge generic agents on a case-by-case basis, said Shari Dermer, Ph.D., a former biotech scientist and organizer of a December follow-on biologics workshop cosponsored by the FDA and the New York Academy of Sciences. But before that can happen, Congress will need to create the legal authority the FDA needs to base the approval of generic proteins on data collected during testing of branded products, she said. Generic versions of more simple molecules, such as human growth hormone, may require relatively little additional proof to meet FDA's needs compared with some more complex biologics, but the standards for abbreviated approval of biologics in general are likely to be more stringent than what the agency requires for standard, more easily defined drugs, she said. "Omnitrope is going to be a bellwether of what might happen in the U.S., " said Dermer. --Joel B. Finkelstein. A Medicare drug plan may counter a doctor's statement that a drug is medically necessary using its own medical and scientific evidence on a particular medication's safety and efficacy in treating certain conditions. Problem: Mr. R was undergoing treatment for hepatitis C. The treatment, however, caused anemia, making him too weak to endure the regimen. In order to boost his red blood cell count, his doctor prescribed Procrit injections. His drug plan rejected both his exception request and redetermination request due to a prior authorization requirement that stated that the plan only covered Procrit for people who had HIV, non-myeloid cancer, myelodysplastic syndrome, or chronic renal failure and protriptyline.
Table 5. Values on aggregates for negative, positive and somatic items at base-line and after highest dose of flumazenil.

Kincora was the home of Brian Boru, the first "High King" to unite the tribes of Ireland. During Boru's twelve-year reign from 1002 to 1014, Kincora served as the capital of Ireland, a critical crossroads of commerce and progressive planning for the future of the country. Inspired by the Kincora of old, Kincora will be a "Class A" employment center located at the crossroads of the County's education Route 7 ; and its commercial Route 28 ; corridors. Kincora has employed smart growth development concepts in this new 424-acre tract of land located at a critical crossroad, where an exploding education research corridor and the region's fast-paced, high-tech employment corridor converge, minutes North of Dulles Airport. A natural venue for collaboration between research and applied technologies, Kincora will be a mixed-use community serving educational, research and high-tech organizations that call Loudoun County home. A 185-acre natural park within the Broad Run watershed will be preserved at Kincora, a permanent legacy to Loudoun's rural heritage. Sleek, high-profile office buildings will line the Property's Route 28 frontage, beckoning the nation's most highly-educated work force and taking advantage of the area's premier transportation infrastructure. Moving west, the scale of buildings will step down into a pedestrian-friendly Village Center where single-story restaurants and open air markets buffer the natural parkland to the west. Loudoun's educational and research community will be served by hotel and conference center uses; residential facilities for students, researchers and executives-in-training; and a resource center, all designed to provide a seamless interface between working and learning and supporting the mission of Loudoun's burgeoning education and research sector. A continuing care retirement center targeting professors and researchers will capture and engage the enduring contribution of a talented workforce. A short stroll from the office buildings, the bustling Village Center will be a gathering point where intellectual capital mixes with business imperatives, providing the raw materials for continual commercial innovation. This blend of live, work and play is essential to create the energy and environment necessary to attract Class "A" tenants in the 21st century. Amenity retail establishments will provide the shops, eateries and services to meet day-to-day needs, all within a short walk from the office. Catering to an active, outdoor-oriented lifestyle, specialty retailers will take up residence in the storefronts of the Village Center. An open air amphitheatre situated along the natural park will provide an attractive backdrop for concerts and public events in a natural pastoral setting. Mindful of the need for balance in life, the 185-acre park along the length of Broad Run will be a significant resource for recreation and reflection in the rural tradition that is the hallmark of Loudoun County. A wetlands trail, designed to be sensitive to the indigenous fauna and flora, will appeal to bikers, joggers and strollers alike. Ultimately connected with the W&OD trail to the south and Loudoun County Parkway to the northwest, the park at Kincora will be accessible to outdoor enthusiasts throughout the Northern Virginia region and provigil.
Weight's influence of the frequency of reproductive complications Eidbo 1996b ; concluded that females as small as 100 g were able to perform mating but when below 150 g the frequencies of egg binding and infer-tile eggs were significantly higher than in heavier females. It was also shown that small fe-males gave birth to small offspring, which were more problematic to get started feeding. On the contrary Tryon and Murphy 1982 ; found the largest and most oblong eggs in the smallest clutches. If problems of initiating breeding are encountered there are a few tricks worth men-tioning. A newly shed skin from another male placed with the breeder male or placing two males together to induce battle have been known to stimulate males Eidbo, 1996b ; . A light shower of the terrarium or a low barometric pressure before a storm also usually stimulates copulation. It is recommended to keep only one breeding pair per cage since more males may interfere and complicate breeding Trutnau, 1990 ; . During the peak of the breeding season and by the end of the gestation period the appetite of males and females, respectively, tends to decrease or stop. It is therefore important to feed them enough for them to have enough energy for this coming taxing period of time. The number of molts before mating has been under some debate. Some breeders think that some females, in particular wild caught, do not breed until their first shedding Eidbo, 1996b ; while others are of the opinion that the preceding molts are not important as long as the female ovu-lates Merker and Merker, 1996 ; . Females breed during the course of two to four weeks Merker and Merker, 1996 ; and after a mating has taken place I usually take a sperm sample to investigate the males fertility under a microscope magnification 100 x ; . The gestation pe-riod lasts for 27-51 days Tryon and Murphy, 1982 ; and by the end of this period the eggs are easily seen as bulges on the rear two thirds of the female's body and are easily palpable. The female sheds six to eleven usually eight ; days prior to oviposition Merker and Merker, 1996 ; . During this pre-laying slough or a little earlier, when the female starts turning grey, I usually provide her with a moisture box. This consists of a semitransparent plastic box half filled with damp vermiculite and an entrance hole cut in the side. It is important not to disturb the female during oviposition since problems such as egg retention may result Eidbo, 1996b ; . Just prior to hatching the eggs may shrink a little Cranston, 1991 ; . Aggressive behaviour of the female when trying to remove the eggs has been reported Assetto, 1978 ; but this is something I have never witnessed. Most of my females eat the same day after oviposition and then shortly turn grey again. See Figure 9 for an illustration of a female coiling around a clutch of newly deposited eggs. When the eggs have been counted and the weight and length have been recorded they are transferred to a plastic box half filled with damp vermiculite and then placed in an incubator. At a temperature of 28C the incubation period usually is around 65 days. Numerous hobby-ists have reported similar incubation periods, including 5570 days at 28C Mulligan and Mulligan, 1996 ; , 66 days. Lenalidomide Revlimid ; has only shown potential benefit in patients with one particular subtype of MDS Low- to Intermediate-1-risk MDS associated with a specific chromosome 5q ; deletion ; . Potential treatment alternatives for MDS may include: erythropoetin alfa Procrit ; , azacitidine Vidaza ; , thalidomide Thalomid ; and antithymocyte globulin Atgam ; . Allogeneic bone marrow transplant is the only hope for a cure for MDS, however not all patients are candidates for this procedure due to age limitations 65 years ; . Safety concerns with lenalidomide Revlimid ; include potential for birth defects, severe neutropenia thrombocytopenia, and increased risk of pulmonary embolism and deep venous thrombosis. There are ongoing trials that study lenalidomide Revlimid ; in a host of other conditions, which puts it at high risk for off-label use and psyllium!

1. Medalia A, Scheinberg IH: Psychopathology in patients with Wilson's disease. J Psychiatry 1989; 146: 662 Akil M, Brewer G: Psychiatric and behavioral abnormalities in Wilson's disease, in Advances in Neurology, vol 65: Behavioral Neurology of Movement Disorders. Edited by Weiner WJ, Lang AE. New York, Raven Press, 1995, pp 171178 3. Chroni E, Lekka NP, Tsiribri E, Economou A, Paschalis C: Acute progressive akinetic-rigid syndrome induced by neuroleptics in a case of Wilson's disease letter ; . J Neuropsychiatry Clin Neurosci 2001; 13: 531532 Tu J: The inadvisability of neuroleptic medication in Wilson's disease. Biol Psychiatry 1981; 16: 963968 Krim E, Barroso B: Psychiatric disorders treated with clozapine in a patient with Wilson's disease. J Neuropsychiatry Clin Neurosci 2001; 13: 531532. Table 2. Mean monthly treatment costs of folinic acid modulated bolus 5-FU, the De Gramont schedule and PVI 5-FU. + FA ; Chemotherapy Outpatient Inpatient Total mean ; Total median ; 74.16 329.96 292.91 De Gramont scheduled ; 393.38 177.41 1027.14 PVI 5-FU.
The treatment of overactive bladder; REMINYL galantamine HBr ; , for patients with mild to moderate Alzheimer's disease; NATRECOR nesiritide ; , a novel agent approved for congestive heart failure; VELCADE bortezomib ; , an oncology treatment; and CONCERTA methylphenidate HCl ; a product for the treatment of attention deficit hyperactivity disorder. MEDICAL DEVICES AND DIAGNOSTICS The Medical Devices and Diagnostics segment includes a broad range of products used by or under the direction of physicians, nurses, therapists, hospitals, diagnostic laboratories and clinics. These products include Ethicon's wound care and women's health products; Ethicon Endo-Surgery's minimally invasive surgical products; Cordis' circulatory disease management products; LifeScan's blood glucose monitoring products; Ortho-Clinical Diagnostics' professional diagnostic products; DePuy's orthopaedic joint reconstruction, spinal and sports medicine products and Vistakon's disposable contact lenses. Distribution to these health care professional markets is done both directly and through surgical supply and other dealers. GEOGRAPHIC AREAS The international business of Johnson & Johnson is conducted by subsidiaries located in 56 countries outside the United States, which are selling products in virtually all countries throughout the world. The products made and sold in the international business include many of those described above under "Business -- Consumer, Pharmaceutical and Medical Devices and Diagnostics." However, the principal markets, products and methods of distribution in the international business vary with the country and the culture. The products sold in international business include not only those which were developed in the United States but also those which were developed by subsidiaries abroad. Investments and activities in some countries outside the United States are subject to higher risks than comparable U.S. activities because the investment and commercial climate is influenced by restrictive economic policies and political uncertainties. RAW MATERIALS Raw materials essential to Johnson & Johnson's operating companies' businesses are generally readily available from multiple sources. PATENTS AND TRADEMARKS Johnson & Johnson has made a practice of obtaining patent protection on its products and processes where possible. Johnson & Johnson owns or is licensed under a number of patents relating to its products and manufacturing processes, which in the aggregate are believed to be of material importance in the operation of its business. Sales of the Company's two largest products, PROCRIT and RISPERDAL, each accounted for over 5% of Johnson & Johnson's total revenues for 2004. Accordingly, the patents related to these products are believed to be material in relation to Johnson & Johnson as a whole. During 2004 and 2005, DURAGESIC fentanyl transdermal system ; in the United States and EPREX in international markets have lost or will lose their basic patent protection and will be subject to generic competition. The pediatric exclusivity for the DURAGESIC patent expired in the U.S. in January 2005. The first generic version of DURAGESIC has been launched. Foreign patent protection related to DURAGESIC will expire during 2005. The Company expects that DURAGESIC sales will decline in 2005 as compared to 2004. During 2004, patents related to EPREX in certain international markets expired. Generic competition will be limited in the near term due to the lack of biologically equivalent compounds. Sales of DURAGESIC and EPREX accounted for over 7% of Johnson & Johnson's worldwide sales in 2004. There are no other major product patents that are scheduled to expire during the next 2 years. Johnson & Johnson has made a practice of selling its products under trademarks and of obtaining protection for these trademarks by all available means. Johnson & Johnson's trademarks are protected by registration in the United States and other countries where its products are marketed. Johnson & Johnson considers these trademarks in the aggregate to be of material importance in the operation of its business. 2.