domingo, 27 de julho de 2008

Antibióticos e Longevidade: o primeiro uso da penicilina

No Annals of Internal Medicine há o relato da primeira administração de penicilina a uma mulhere de 33 anos morimbunda por infeçção por estreptococos. Ela morreria de outra causa aos 90 anos.
The first use of penicillin in the United States occurred in 1942 and saved a moribund patient who had [beta]-hemolytic streptococcal sepsis.
The first dose of penicillin given in the United States was administered at Yale–New Haven Hospital on 14 March 1942 to a patient dying of septicemia. As a young Yale house officer, I found myself involved in what few of us then realized was a very profound sequence of events. It was my ninth month of service, and I was an acting assistant resident.
On the private floor of the Yale–New Haven Isolation Building, a very ill 33-year-old patient had [beta]-hemolytic streptococcal sepsis. She had run a steady temperature of 103° F to 106° F for 4 weeks Her private physician, Dr. John Bumstead, persuaded Dr. John F. Fulton, another ill patient of his with a severe pulmonary infection, to try to obtain a new drug—penicillin. The drug was not yet available in the United States. Dr. Howard Florey had reported on the use of penicillin in England in 1941, and Dr. Fulton was aware of Florey’s studies. Since their Oxford days together, Fulton and Florey had remained friends. In fact, Dr. Florey’s children were living with the Fultons in New Haven, Connecticut, to escape the German bombs falling on London in 1941.
-Dr. Fulton, a National Research Council (NRC) Committee on Aviation Medicine member and Sterling Professor of Physiology, and Dr. Francis G. Blake, Sterling Professor of Medicine and a leading member of the National Academy of Science Chemotherapy Committee, used their considerable influence to complete the tortuous route required to release the small amount of penicillin available in the United States. Dr. Florey and his associate, Dr. Norman Heatley, had come to the United States in an effort to increase penicillin production, because England was so busy with the war with Germany.
The first vial was mailed to Dr. Bumstead in New Haven from Merck & Co. in Rahway, New Jersey, and it arrived on Saturday, 14 March 1942. Dr. Bumstead and I took the vial to Dr. Morris Tager, Associate Professor of Bacteriology and Immunology. We discussed what to do with the pungent, brown-red powder. “We decided to dissolve it in saline and pass it through an E.K. Seitz [asbestos] filter pad to sterilize it,” wrote Dr. Tager in 1976. We then returned to the patient, and I injected 5000 U into the intravenous tubing. Rocko Fasanella, a medical student (later a professor of ophthalmology at Yale), gave subsequent doses every 4 hours. By Monday morning, the patient was eating hearty meals, the intravenous treatment was stopped, and she subsequently received 5000 U intravenously every 4 hours. On Monday morning rounds, Dr. Wilder Tileston, a senior consultant, looking at the temperature chart, muttered to those of us close enough to hear, “black magic.” My fellow intern, Dr. Herbert Tabor (later the editor of the Journal of Biological Chemistry for many years), saved all of the patient’s urine because Dr. Heatley had informed us that more penicillin could be purified from it than could be produced by cultivation.
Probably up to 95% of each intravenous dose was excreted unchanged. When Dr. Heatley delivered a subsequent vial, some of which had come from the patient’s urine, he carted the gallons of urine back to Rahway. The patient survived and later died of other causes at the age of 90 years.
Four hundred million units of penicillin were produced in the first 5 months of 1943. In the next 7 months, 20.5 billion units were produced—an increase of more than 500 times. By August 1945, 650 billion units were distributed each month. The subsurface liquid culture technique produced so well that when the structures of penicillin F and G were later established, it was decided that producing penicillin by culture rather than by any chemical synthetic method would be far less costly. Production costs changed so that the cost of an ampoule of 100 000 units was “scarcely more than the cost of material and labour to put it into an ampoule” If any one person is to be credited with the development of penicillin in the United States, it should be Dr. John F. Fulton. The literature does indeed tell about his significant role. His telephone calls from his own hospital bed demonstrated his persistence, perspicacity, patience (when needed), propriety, and personal influence. He recognized a need and a possible fulfillment of this need, and he effectively pushed for the sequence of events that transpired. Fleming, Florey, and Chain received the Nobel Prize in Medicine in 1945 for their contributions. Fulton deserves credit together with Dr. Francis G. Blake for proving the enormous value of penicillin and effecting the birth of the antibiotic era

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