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Vincent Butler
Professor Emeritus Medicine; Special Lecturer in Medicine
630 W168th St, 10-445A, New York, NY 10032
Phone: (212)305-4059
Fax: (212)305-3475
Email:vpb2@columbia.edu

Dr Vincent P Butler Jr, has retired as Director of the Immunology Division of the Department of Medicine and is now a member of the Division of Clinical Pharmacology and Experimental Therapeutics.

Dr Butler has had a long-standing interest in the application of immunochemical approaches to problems of clinical medicine.  In the mid-1960’s, he addressed a major clinical problem with the use of digitalis glycosides, drugs which are still very important today and which were then the mainstays of the therapy of congestive heart failure.  The problem was that, in patients with advanced heart disease (in whom the need for digitalis was greatest), serious cardiac toxicity was a major problem, with hundreds (perhaps thousands) of deaths annually in the United States.  As noted in 1967 by Dr Butler ¹, not
only was no specific antidote available, but also “no convenient method [was then] available for the specific determination of cardiac glycosides in plasma and tissue fluids.”  With these problems in mind, Dr Butler proposed that “[d]igitalis-specific antibodies could conceivably be an extremely useful tool (1) in the immunological assay of digitalis in plasma and tissue fluids, (2) in the therapy of severe digitalis toxicity, and (3) in the study of the mechanism of action of digitalis.”  Dr Butler then developed the first antibodies to digoxin, a digitalis glycoside¹, enabling the reversal of
experimental digitalis toxicity^2,3 and the development of a serum digitalis immunoassay⁴.  Today, more than four decades later,
these antibodies are still used extensively in assays for the clinical management of digitalis therapy, while Fab fragments of these antibodies (known as “Digibind”) are the mainstay of therapy for potentially lethal digitalis intoxication⁵.  Dr Butler and his
colleagues have also used these antibodies in identifying important factors responsible for dangerously wide variations in digitalis dosage requirements, notably major differences in bioavailability of different digitalis preparations⁶ and differences in
the metabolism of digitalis by the gut flora of different individuals^7,8.

In more recent years, Dr Butler has been engaged in studies of the physiological role of cardiotonic steroids (known as bufadienolides and bufotoxins) found naturally in the tissues and body fluids of bufonid toads ^9,10.

Currently, Dr Butler is working with Dr Milan Stojanovic of this division in the development of methods for the targeted tumor-specific delivery of cytotoxic bufadienolides, using methods designed to spare normal non-tumor tissues from the toxic cellular actions of these bufadienolides.

Selected Publications

1. Butler VP, Jr., Chen JP.  Digoxin-specific antibodies.  Proc Nat Acad Sci USA 57:71-78,1967.
2. Butler VP, Jr.  Digoxin: Immunologic approaches to measurement and reversal of toxicity.  N Engl J Med 283:1150-1156,1970.
3. Schmidt DH, Butler VP, Jr.  Reversal of digoxin toxicity with specific antibodies.  J Clin Invest
   50:1738-1744,1971.
4. Smith TW, Butler VP, Jr., Haber E.  Determination of therapeutic and toxic serum digoxin concentrations by radioimmunoassay.  N Engl J Med 281:1212-1216,1969.
5. Antman EM, Wenger TL, Butler VP, Jr., Smith TW.  Treatment of 150 cases of life-threatening digitalis intoxication with digoxin-specific Fab antibody fragments: final report of a multicenter study.   Circulation 81:1744-1752,1990.
6. Lindenbaum J, Mellow MH, Blackstone MO, Butler VP, Jr.  Variation in biologic availability of digoxin from four preparations.  N Engl J Med 285:1344-1347,1971.
7. Lindenbaum J, Rund DG, Butler VP, Jr., Tse-Eng D, Saha JR.  Inactivation of digoxin by the gut flora: reversal by antibiotic therapy.  N Engl J Med 305:789-794,1981.
8. Dobkin JF, Saha JR, Butler VP, Jr., Neu HC, Lindenbaum J.  Digoxin-inactivating bacteria: identification in human gut flora.  Science 220:325-327,1983.
9. Butler VP, Jr., Morris JF, Akizawa T, Matsukawa M, Keating P, Hardart A, Furman I.  Heterogeneity and lability of endogenous digitalis-like substances in the plasma of the toad, Bufo marinus.  Am J Physiol 271:R325-R332,1996.
10. Morris JF, Ismail-Beigi F, Butler VP, Jr., Gati I, Lichtstein D.  Ouabain-sensitive Na+,K+-ATPase activity in toad brain.  Comp Biochem Physiol 118A:599-606,1997.
    

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