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C K M Chan, S Mohamed, M P Shanmugam, C-W Tsang, T Y Y Lai, D S C Lam, Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong C K M Chan, S Mohamed, M P Shanmugam, C-W Tsang, T Y Y Lai, D S C Lam, Hong Kong Eye Hospital, 147K Argyle Street, Kowloon, Hong Kong Financial support: nil. Competing interests: nil. Financial and proprietary interest: nil. Ethical approval: The patients in this study participated in clinical trials which had ethical approval from the Chinese University of Hong Kong Clinical Research Ethics Committee and the research was carried out according to the tenets of the Declaration of Helsinki. Informed consent was obtained from all patients. Presentation: The data in this paper were presented in part at the Annual Scientific Meeting of the Hong Kong Ophthalmological Society 35 Dec 2005, Hong Kong ; and the 21st Congress of the Asia Pacific Academy of Ophthalmology 1014 June 2006, Singapore.
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1. KATZ, R. L. & EPSTEIN, R. A. The Interaction of Anesthetic Agents and Adrenergic Drugs to Produce Cardiac Arrhythmias. Anesthesiology. 29: 763 1968 ; . 2. JOHNSTONE, M. Propanolol Indeal ; during Halothane Anaesthesia. Brit. J. Anaesth. 38: 516 1966 ; . 3. SHARMA, P. L. Effect of Propranolol Non-Catecholamine-Induced Arrhythmias during Nitrous Oxide-Halothane Anaesthesia in Dog. Brit. J. Anaesth. 38: 871 1966 ; . 4. WARNER, W. A. Beta-Adrenergic Blocking Agents and Anaesthesia: A Review. Canad. Anaesth. Soc. J. 15: 42 1968 and adalat.
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44 HE ALTH AFF AIRS prod uct, and not merely the specific new use which is subject to regulatory review. S. 255 contains the following limitation with respect to the scope of any patent extension: The rights derived from any claim or claims of any patent so extended shall be limited in scope during the period of any extension to the product or method subject to the regulatory review period and to the statutory use for which regulatory review was required. Since the extended rights are limited to "the product or method" and not "the product and method" which is subject to regulatory review, a product patent claim would be enforceable against all methods of using that product for therapeutic purposes, both old and new, during the period of any extension, The prospect of seven additional years of monopoly prices on an important drug such as Valium can certainly justify a large expenditure of research dollars on an unimportant new use for that composition as a means of extending patent life for the commercially significant old uses. Moreover, as a result of experience gained by the medical community in using an approved drug for an approved indication, it is not uncommon for significant new therapeutic uses to be discovered, and these discoveries need not necessarily result from the efforts of the original patent owner. The discovery that Ijderal propranolol ; is useful in limiting the size of a heart attack among high risk patients is a recent example of such a discovery which was funded by the government. Is the owner of the Inderwl patent now properly entitled to up to seven years of additional patent protection on the product simply because it now files an NDA for the independently discovered new end use? Is there any justification for granting an extension of a scope that would provide monopoly power and monopoly prices over the original end uses of Inderwl as to which the innovator has already obtained the full benefits of a patent monopoly? Will companies other than the original patentees invest time and money in developing new uses for previously patented drugs, if the discovery of those new uses will lead to extensions of the original patents, thereby blocking them from commercially exploiting the new uses? The legislation does not even recognize that these problems exist, let alone deal with them in any effective manner. To the extent that government regulation causes delay in bringing products to market, that problem should be addressed and solved. The solution to the problem does not, however, reside in tampering with the patent system in a manner which will create broad new monopoly rights that extend well beyond any real or imagined problem caused by premarketing regulation of drug products.
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Dear Annie: My husband and I are in our late 70s. Although we had a modest income, we managed to send all our children to college, and they now are financially comfortable. We have been retired for several years and are on a limited income. My children like to come home for every holiAnnie's day, and Mailbox we enjoy having them. The problem is the food. They all help with the preparation and clean-up, the reason for your fluttering. You need shaving, waxing and plucking? more testing, including blood analyses for Dear Reader: Although most cases of but menus and shopping anemia and an overactive thyroid gland. unwanted excess body hair in women are have become an obstacle. Inderal is a beta-blocker that slows the -- unfortunately -- genetically dictated, As my children marry and heart rate. It is appropriate therapy for some instances may be caused by a viriliz- have children, it is becoming your condition, but I concerned that ing tumor. Such a growth, which produces increasingly difficult to preyour testing appears to be incomplete. The excessive quantities of the male hormone pare meals for the extended fact that your abnormal cardiac rhythm testosterone, may arise in the adrenal family. One eats only kosher returned when the medication was glands, the ovaries or elsewhere in the food, another has an allergy stopped means that the cause of your pal- reproductive tract. to milk, one has high cholespitations is still a mystery. Also, enlargement of the adrenal glands, terol, another is diabetic, Although your family doctor could cerso-called "congenital adrenal hyperplasia, " one hates vegetables, and tainly order the necessary testing, I can cause inappropriate hair growth in a one is on the South Beach believe that a second opinion is in order. typically male pattern. Finally, polycystic Diet. Some want skim milk, Thus, I recommend that you see a cardiol- ovaries Stein-Leventhal syndrome ; can others want soy, and each ogist. Let me know how this situation is cause virilization. child wants his favorite soda resolved. You definitely should be examined by and favorite cereal. Some Dear Dr Gott: For the past several your family physician or an endocrinoloyears I've had steadily increasing amounts gist ; and undergo blood and urine testing, eat no breakfast, so they snack or want an early dinof body hair appear on my face, neck, as well as a CT scan and ultrasound. back, shoulders, arms and chest. I now As a general rule, the disorders I menshave my chin and neck twice daily -- not tioned can be cured by surgery. an easy accomplishment for a 37-year-old NEA Inc. Write to Dr. Peter Gott, female. Can a doctor help me with this, or c o United Media of 200 Madison Ave I faced with no remedy other than 4th Floor, New York City, NY 10016 and echinacea.
In the early part of 2000 we will build up a Bandolier Alternative Therapy website with the results of all the systematic reviews we can find. It's a lot of work, we have no fund2.
Coding Exercises for S9. Medications Complete the practice form on the next page for the following medications during a 30-day period 8 11 029 ; : Inderal 40 mg. BID p.o. 2. Sinemet 10 100 TID p.o. 3. Artificial Tears 1 drop OU QID 4. Anusol HC suppository 1 PRN given 1 time in last 30 days ; 5. Amoxicillin 500 mg q 6 hrs per tube 6. Benylin cough syrup 2 tbs. PRN p.o. given 10 times in last 30 days ; 7. Darvocet-N 100 2 tabs q 4-6 hrs PRN p.o. given 5 times in last 30 days ; 8. Heparin lock flush 10 U daily 9. Ditropan syrup 2.5 mg daily p.o. 10. Nitrotransdermal .4 mg 1 patch daily 11. Novolin N 24 U before breakfast SQ 12. Check blood sugar before breakfast. Sliding scale insulin: Novolin R 10 units if blood sugar over 200. 10 units given on 2 days in last 30 days ; 13. Questran 1 packet with each meal p.o. 14. Quinine sulfate 325 mg. HS 15. Coumadin 2.5 mg daily p.o. discontinued 9 3 02 ; 16. Coumadin 5 mg. daily p.o. ordered to start on 9 4 17. Maalox 15 cc PRN for indigestion p.o. not administered in last 30 days ; Complete the practice form and compare your form with the answers on the next page 2. RA 3. Freq 4. PRN-n and pilocarpine.
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Let's assume that the merger mania will create 5 giant pharmaceutical companies in the world. Each will have one statin, one pril, one betablocker. Each of the companies will not make the second betablocker, since it costs a lot to promote the second medicine, and sales of the second medicine will reduce sales of the first one. The merger mania will not only reduce the number of new medicines, but also the number of better medicines; it will inhibit progress in pharmacy and medicine. It is easy and simple to demonstrate using an example e.g. betablockers. The first Propranolol produced by ICI Inderal ; induced admiration. It was a financial success for the company. Other companies also wanted profit. The congeners followed: Ciba's Oxprenolol Trasicor ; , Sandoz's Pindolol Visken ; , Merck's Timolol Timoptic ; . If there were only few companies, this would have been it. But there were many companies, each developing its own betablocker. Owing to this process, luckily, we obtained selective betablockers: ICI's Atenolol Tenormin ; , Astra's Metoprolol Beloc ; , Specia Rhne-Poulenc's Acebutolol Sectral ; , which contributed to progress in cardiology. These examples show that mergers decreasing the number of companies capable of competiting in terms of invention is not in the interest of health. It seems that there is time to ensure a more careful anti-monopoly supervision over mergers in the pharmaceutical industry. Certainly the pharmaceutical companies' need for mergers will not disappear. On the contrary, it will be getting stronger, as the profits generated by new patented medicines are growing and so is the fear of breakdown after patent expiration. This fear must be discharged through subsequent mergers. Governments and parliaments in developed countries can oppose this process by refusing consent to mergers of those great companies that are capable of inventing new medicines on their own.
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Inducible activation of a p53 R172H allele accelerates mouse skin carcinogenesis C Caulin, 1 G Lang, 2 G Lozano2 and DR Roop1 1 Departments of Molecular and Cellular Biology and Dermatology, Baylor College of Medicine, Houston, TX and 2 Department of Molecular Genetics, University of Texas M.D. Anderson Cancer Center, Houston, TX Most of the p53 mutations found in human tumors are missense mutations that result in the expression of altered forms of p53. Previous mouse models overexpressing the mutant, p53 R172H, in the epidermis suggested that this mutant p53 promotes carcinogenesis through gain-of-function activities. Since the p53 R172H transgene was expressed at levels 4-8 fold higher than wild type p53, it was unclear whether p53 R172H functions as a true gain-of-function mutation in the genetic sense. To ultimately address this question we have generated transgenic mice expressing one p53 R172H allele in the presence of a wild type allele exclusively in the epidermis. The p53 R172H allele remains silent until activation by an inducible Cre recombinase placed under the control of the keratin 5 promoter. After topical application of an inducer RU486 ; Cre is activated, which results in focal activation removal of a floxed stop cassette ; of the p53 R172H allele in epidermal stem cells. Mice expressing the p53 R172H allele were subjected to a skin carcinogenesis protocol. These mice develop tumors faster than control wild type littermates. In addition, the rate of progression to malignant carcinoma was also dramatically accelerated in mice expressing the p53 R172H allele 70% conversion of p53 R172H allele tumors vs. 0% of wild type control tumors; 32 wk. after initiating promotion ; . Furthermore, carcinomas arising in mice that express the mutant p53 R172H allele were shown to metastasize to lymph nodes and lungs. Immunological staining confirmed that mutant p53 was expressed in the epithelial component of tumors at all stages of tumor development and progression. This model provides the strongest in vivo data to date that the p53 R172H allele exhibits a true gain-of-function at the genetic level.
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