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FREDERIC C. BARTTER September 10, 1914—May 5, 1983 BY JEAN D. WILSON AND CATHERINE S. DELEA FR E D E R I C C R O S B Y B A R TT E R was born in the Philippine Islands on September 10, 1914, ant! cried in Washington, D.C., on May 5, 1983, of complications resulting from a ce- rebral hemorrhage that occurred while he was attending the annual meeting of the National Academy of Sciences. With his death, clinical science lost one of its most imaginative in- vestigators anc! charismatic personalities. His achievements were both broad and deep. He devoted a major portion of his career to investigating the interrelation between the kicI- ney and various endocrine systems and contributed to aspects of clinical science as diverse as chronobiology, the physiology of taste and smell, and mushroom poisoning. At the National Institutes of Health he collaborates! with more than a hun- dred investigators (friends), enriching the lives ant! scientific stature of each through his ability to stimulate, guide, and enhance the talents of others. EARLY LIFE George Bartter, an Anglican minister from England, and his wife, Frances Buffington, an American teacher, had two children—George and Frederic both born in Manila and raised in the remote mountain village of Baguio, Philippine Islands, which became the family home. Bartter's early eclu- 3

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4 BIOGRAPHICAL MEMOIRS cation was supervised by his father, his mother (a Smith col- lege graduate and classical scholar), and priests at a nearby Catholic monastery. Early in life he acquired a love of poetry and good writing and, in later years, was able to recite from memory long passages from Shakespeare, St. Teresa, and Rupert Brooke. At age thirteen he and his brother were sent to the United States and enrolled at the Lennox School in Lennox, Massachusetts, from which he graduated in 1930. He returned to the Philippine Islands for a year and worked in the English school before entering Harvard College. After receiving a Bachelor of Arts degree in 1935, Bartter spent a year in the Department of Physiology, Harvard School of Public Health. His interest in an investigative career and his first paper on lymph sugar stemmed from this experience. He obtained his M.D. degree from Harvard Medical School in 1940 and spent his internship at Roosevelt Hospital in New York from ~ 94 ~ to ~ 942. ACCOMPLISHMENTS IN BIOMEDICAL RESEARCH Bartter's first paper after graduation from medical school resulted from his service as an officer in the U.S. Public Health Service during World War Il. The paper concerned plasma volume and the speed with which plasma is reconsti- tuted after donation of blood, the control of blood volume being an important topic throughout his subsequent career. The Public Health Service then assigned him to the Pan American Sanitary Bureau to investigate the physiology of parasitic diseases, one result of which was a pioneering study of the treatment of onchocerciasis. There can be no doubt that both the style and the focus of his investigative career were profoundly influenced by his subsequent association with Fuller Albright, first as a re- search fellow from 1946 to 1950, then as a junior member of the faculty at the Massachusetts General Hospital and the

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FREDERIC C. BARTTER 5 Harvard Medical School. Many have described the unique environment Fuller Albright created on Ward Four at the Massachusetts General Hospital, including Bartter, who wrote several moving accounts. At least three distinguishing features of Bartter's work stem directly from his relationship with Albright. First, he performed virtually all of his work directly on humans. In- deed, his bibliography of over 400 papers lists only a few studies using experimental animals and fewer still experi- ments in vitro. Though clinical physiologists usually draw clinical decluctions from animal studies, Albright, whose mode} Bartter followed, deduced physiological principles from physiology deranged by the disease process. Secondly, Bartter used few patients in each study, but every patient was studier! intensively over a long period of time with the most advanced methodologies and techniques. Finally, Bartter benefitted from his mentor's remarkable breadth of interests that encompassed electrolyte ant! renal physiology, endocri- nology, intermediary metabolism, the control of blood pres- sure, biological rhythms, and neurophysiology. The last of a school of clinical investigation built on the metabolic balance technique, Bartter was yet uniquely adept at applying new technologies to in viva studies, from isotope dilution to radioimmunoassay procedures. During his years with Albright, Bartter developed a num- ber of interests that would continue throughout his career: the metabolic effects of ACTH in man, parathyroid patho- physiology ant! bone metabolism, the control of blood vol- ume in disease, and the metabolic effects of androgens, es- trogens, and adrenocortical steroids in various disorders. An outstanding example of Bartter and Albright's joint ~ See "Fuller Albright," in The Massachusetts General Hospital, 1955-1980 (Boston: Little Brown & Company, 1981), p. 86; and "Fuller Albright," Endocrinology 87 (1970): 1 109.

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6 BIOGRAPHICAL MEMOIRS creativity was their deduction that the common virilizing form of adrenal hyperplasia is funciamentally a type of adre- nocortical insufficiency arising from a metabolic error in the biosynthetic pathway for cortisol. To compensate for the de- ficiency in cortiso! secretion, they reasoned, the pituitary se- cretes excessive quantities of ACTH leading to excessive se- cretion of other classes of adrenal steroids by the adrenals themselves. Bartter and Albright proved their thesis by treat- ing affected patients with cortisone to correct the hyperse- cretion of virilizing steroids undoubtedly the single great- est stroke of genius in understanding and controlling adrenal hyperplasia. In 1951, Bartter's move from Boston to the National In- stitutes of Health, initially in Baltimore and then Bethesda, broadened the focus of his studies of the pathophysiology of disease. When "electrocortin" (aldosterone) was discoverer! in 1953, it was immediately apparent to Bartter that this new hormone must be of critical importance in cardiovascular- renal physiology. He turned his attention to determining its role in health and disease and the factors controlling its secretion. Without neglecting the importance of other al- dosterone regulatory factors, Bartter, together with Grant Kiddie, reasoned that extracellular fluid volume is a major determinant of aldosterone secretion. This deduction ulti- mately led several groups to the discovery that the aldoste- rone regulatory influence of extracellular volume is mediated by the renin-angiotensin system. In 1960, Bartter described the syndrome of hyperplasia of the juxtagIomerular complex in which hyperaldoste- ronism and hypokalemic alkalosis coexist with normal blood pressure: now commonly termed Bartter's syndrome. His findings added to the growing body of evidence that aclrenal cortical secretion is influenced by the renin-angiotensin sys- tem. He further proposed a hypothesis for the paradox of

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FREDERIC C. BARTTER 7 normal blood pressure in the presence of high concentra- tions of aldosterone and angiotensin, a paradox still being investigated today. Adrenal hyperplasia, with all its complexities, held a con- tinuing fascination for Bartter. He realized that a thirc! of all the patients he studied with primary alclosteronism also had adrenal hyperplasia. Originally it was hoped that plasma renin determinations might differentiate between aldoste- ronism produced by tumor from that proclucecl by hyperpla- sia. The low plasma renin values measured in several patients with proven adrenal hyperplasia suggested that, in these pa- tients, all adrenal tissue responds to a tropic stimulus other than ACTH or the renin-angiotensin system. This, too, con- tinues to be an active field! of investigation. While many of the seventy papers on calcium and phos- phorus metabolism coauthored by Bartter relate to the di- agnosis and treatment of hyperparathyroidism, pseuctohy- poparathyroictism, and metabolic bone cliseases, several significant studies clear with the renal handling of phospho- rus ant! calcium under the influences of parathyroid hor- mone, vitamin D, large doses of phosphate, and calcium in- fusions. Bartter's laboratory also explored the physiology of thyrocalcitonin and its relation to disease states, the solubility ant! composition of bone mineral, anc! the gastrointestinal absorption of calcium and its role in metabolic diseases. In the late 1960s he and Charles Y. C. Pak began a pioneering series of studies on the classification, pathogenesis, and treat- ment of kiciney stones. During these years at the N]:H, Bartter's studies coverer! a broad range of metabolic topics: renal concentrating mech- anisms, steroid-hormone binding anc} transport, urinary acidification mechanisms, regulation of aldosterone biosyn- thesis, the effect of adrenal hormones on taste and auditory threshoIcis, vitamin D metabolism and action, phosphorus

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8 BIOGRAPHICAL MEMOIRS depletion, mechanisms of edema formation, cystine metab- olism, magnesium metabolism, radiographic measurements of bone minerals, prostaglandin and catecholamine metabo- lism, and collagen formation in bone. The common theme in all these studies was Bartter's passion for analyzing the dis- ease process. A highlight of his investigative career came in 1957, when with William B. Schwartz of Tufts University he de- scribed the syndrome of inappropriate secretion of anti- diuretic hormone (ADH, or vasopressin). Hyponatremia and renal sodium loss unrelated to renal or adrenal disease were seen in two patients with bronchogenic carcinoma. The data from a series of studies of these patients suggested overex- pansion of the body fluids, probably as a result of sustained, inappropriate secretion of ADH. Bartter and Schwartz char- acterized this clinical entity, now known to occur in a variety of pathophysiological settings, in a trenchant series of clinical experimental and didactic studies developed over more than two decades. The syndrome is found with various tumors; in disorders affecting the central nervous system or the lungs; and in adrenal, thyroid, or pituitary insufficiency. It is now known that the tumors produce an antidiuretic substance di- rectly and that some of the other disorders are associated with an abnormal release of ADH from the pituitary gland. From its immediate impact upon medicine, Bartter's descrip- tion of inappropriate ADH secretion was perhaps his most · , - mportant discovery. During the last decade of his scientific career, Bartter fo- cused on the control of blood pressure and the derangements that underlie the hypertensive disorders of man—a line of investigation that continued after his 1978 move to the Uni- versity of Texas Health Science Center in San Antonio and was cut short by his untimely death. It is an irony that he discovered his own hypertension during these studies.

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FREDERIC C. BARTTER PERSONAL QUALITIES 9 Fred Bartter's curiosity and quest for intellectual expan- sion extender} well beyond his professional interests. He had a great love and knowledge of music and sang with several musical groups, an interest he sharer! with his family. A clevo- tee of mathematician and philosopher Alfred North White- head (under whom he studied), he read widely in philosophy and poetry. He was a perpetual student who insisted, both in his public speaking and writing, that clarity of expression reflects clarity of thought. He was a strict adherent of correct grammar, and everyone who worked with him became aware of his meticulous attention to detail. Yet his subtle sense of humor, his joy in and excitement about life on the day-to-day level, made him particularly endearing. His warmth and sen- sitivity gained him the respect and loyalty of his patients, whom he treated as an integral part of the investigative team. Delighting in the diagnostic pursuit of a disease, he yet never lost sight of the person. One of Bartter's many interests deserves special comment. During a summer vacation he picked up a book belonging to his mother-in-law, who hac! been a botany major at Smith College, about mushrooms. Its beautiful illustrations and the complex classification system of species and subvariants fas- cinatecl him, and he began looking for mushrooms in the woods and lawns back home. Pursuing this subject with the same intellectual vigor he applied to his work, Bartter became an authority on the subject. He conic! identify more than 200 varieties, and for many years he combined his avocation with his professional career, giving lectures on mycology ant! on the symptoms and treatment of mushroom poisoning. Following Czech reports of lipoic acid as an antidote for Amanita mushroom poisoning, Bartter and Charles Becker of the University of California, San Francisco obtained an

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10 BIOGRAPHICAL MEMOIRS investigational permit from the Food and Drug Aciministra- tion to use lipoic acid as a treatment for patients who hac! eaten supposedly lethal mushrooms.2 The toxins of the "Death Caps" (or "Destroying Angels," as cleadly Amanitas are called attack the liver, causing hepatitis and acute yellow atrophy that may progress to liver failure. Bartter ant! Becker treated many patients who had ingested! the mushrooms, ant! were therefore at risk, with the agent. Although the precise therapeutic role of lipoic acid—as opposer! to other sup- portive features of the experimental regimen—was never cIarifiect, the treatment was successful. Bartter's experience with treating mushroom poisoning enhancer! his zest as a mushroom collector, and he delighted! in instructing others and in serving as a resident expert on mushroom identifica- tion. HONORS Fret] Bartter was a member of numerous professional and scientific societies, including the Endocrine Society, the American Society for Clinical Investigation, the Association of American Physicians, the Royal Society of Medicine, the Royal College of Physicians of London, the Peripatetic Club, and the National Academy of Sciences, to which he was elected! in 1979. He received the Sandoz Contemporary Man in Medicine Award, the Modern Medicine Distinguishes! Achievement Award, the Fred C. Koch Award of the Endocrine Society, and the Meritorious Service Medal from the National Insti- tutes of Health. These honors were followed by election as the 1981 honorary faculty member of the Epsilon Chapter of Alpha Omega Alpha—the medical honorary society at the ~ See B. I. Culliton, "The Destroying Angel: A Story of a Search for an Antidote," Science 185(1974):600; and "Dr. Bartter Tries Thioctic Acid as Antidote to Fascinat- ing Fatal Wild Mushrooms," NIH Record (November 4, 1975):6.

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FREDERIC C. BARTTER 11 University of Texas Health Science Center in San Antonio- and, in ~ 982, election as an Honorary Fellow of the American College of Carcliology. In 1982, the American College of Phy- sicians conferred on him the John Phillips Memorial Award "in recognition of his outstanding career as an investigator ant! teacher ant! for his memorable contribution to the understanding of hormonal regulation of renal function and salt and water homeostasis." Bartter was also asked to give many honorary lectures, including the 1980 Arthur B. Corcoran Award of the High Blood Pressure Council and the 1982 Fuller Albright Lecture of the Peripatetic Club. The San Antonio Veterans Acimin- istration Medical Center named its Bartter Clinical Research Center in his memory a posthumous tribute that surely would have pleased him. Frect Bartter is survived by his wife, the former lane Lil- larcI; three children, Frederic C. Bartter, fir., of Baltimore, Dr. Thaddeus C. Bartter of Boston, ant! Mrs. George (Pa- mela) Reiser of Lincoln, Massachusetts; and three grandchil- dren. Fred Bartter will be remembered by his associates for his persistence, imagination, endless curiosity, ant! bottomless fund of knowledge. The ability to perceive a disease in a set of slightly aberrant numbers, the unshakable faith that, in metabolic balance studies, what goes in must eventually come out, and the optimism that all is eventually discoverable- this is "Bartter's Syndrome," and we are all the better for having been exposed to it.

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12 BIOGRAPHICAL MEMOIRS C H RON OLOGY POSTGRADUATE TRAINING AND FELLOWSHIPS 1941-1942 Medical intern, Roosevelt Hospital 1942-1945 Medical officer, U.S. Public Health Service 1945-1946 Staff member, Laboratory of Tropical Diseases, National Institutes of Health 1946-1948 Research Fellow in Medicine, Massachusetts General Hospital 1968-1969 Overseas Fellow, Churchill College, University of Cambridge PROFESSIONAL APPOINTMENTS 1948-1950 Assistant in Medicine, Massachusetts General Hospital 1951 Associate in Medicine, Massachusetts General Hospital 1951-1973 Chief, Endocrinology Branch, National Heart and Lung Institute, National Institutes of Health 1970-1976 Clinical Director, National Heart and Lung Institute, National Institutes of Health 1973-1978 Chief, Hypertension, Endocrine Branch, National Heart and Lung Institute, National Institutes of Health 1958-1978 Associate Professor and Professor of Pediatrics. Howard University 1960-1978 Associate Professor and Clinical Professor of Medicine, Georgetown University 1978-1983 Professor of Medicine, University of Texas Health Science Center, San Antonio, and Associate Chief of Staff for Research, Audie L. Murphy Memorial Veterans Administration Hospital, San Antonio MEMBERSHIPS Endocrine Society Laurentian Hormone Conference American Society for Clinical Investigation Association of American Physicians Salt and Water Club

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FREDERIC C. BARTTER 1953 15 With A. Leaf, R. F. Santos, and O. Wrong. Evidence in man that urinary electrolyte loss induced by pitressin is a function of water retention. I. Clin. Invest., 32:868. 1956 With G. W. Liddle and L. E. Duncan, fir. Dual mechanism regulat- ing adrenocortical function in man. Am. I. Med., 21:380. With L. E. Duncan, fir., G. W. Liddle, and K. Buck. The effect of changes in body sodium on extracellular fluid volume and al- dosterone and sodium excretion by normal and edematous man. }. Clin. Invest., 35:1299. The role of aldosterone in normal homeostasis and in certain dis- ease states. Metabolism, 5:369. With G. W. Liddle, L. E. Duncan, fir., }. K. Barber, and C. Delea. The regulation of aldosterone secretion in man. The role of fluid volume. I. Clin. Invest., 35:1306. 1957 The role of aldosterone in the regulation of body fluid volume and composition. Scand. I. Clin. Lab. Invest., 10:50. With W. B. Schwartz, W. Bennett, and S. Curelop. ~ syndrome of renal sodium loss and hyponatremia probably resulting from inappropriate secretion of antidiuretic hormone. Am. J. Med., 33:529. 1958 With R. S. Goldsmith, P. J. Rosch, W. H. Meroney, and E. O. Hern- don. "Primary aldosteronism" associated with significant edema. l. Clin. Endocrinol., 18:323. With W. E. Schatten, A. G. Ship, and W. I. Pieper. Syndrome resem- bling hyperparathyroidism associated with squamous cell car- cinoma. Ann. Surg., 148:890. 1959 With R. S. Gordon, fir., and T. Waldmann. Idiopathic hypoalbu- minemias: Clinical staff conference at the National Institutes of Health. Ann. Intern. Med., 51:553. With J. Orloff, M. Walser, and T. J. Kennedy, Jr. Hyponatremia. Circulation, 19:284.

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16 BIOGRAPHICAL MEMOIRS With M. M. Pechet and B. Bowers. Metabolic studies with a new series of 1,4-diene steroids. I. Effects in Addisonian subjects of prednisone, prednisolone, and the 1,2-dehydro analogues of corticosterone, desoxycorticosterone, 17-hydroxy-11-desoxy- corticosterone, and 9a-fluorocortisol. l. Clin. Invest., 38:681. 1960 With H. P. Schedl. An explanation for and experimental correction of the abnormal water diuresis in cirrhosis. I. Clin. Invest., 39:248. With I. H. Mills, H. P. Schedl, and P. S. Chen, Tr. The effect of estrogen administration on the metabolism and protein binding of hydrocortisone. I. Endocrinol., 20:515. With W. B. Schwartz and D. Tassell. Further observations on hy- ponatremia and renal sodium loss probably resulting from inappropriate secretion of antidiuretic hormone. N. Engl. I. Med., 262:743. With R. S. Goldsmith and W. H. Meroney. Prominent peripheral edema associated with primary aldosteronism due to an adre- nocortical adenoma. l. Clin. Endocrinol., 20: 1168. 1961 With l. R. Gill, fir. On the impairment of renal concentrating in prolonged hypercalcemia and hypercalciuria in man. l. Clin. Invest., 40:716. With I. P. Thomas. Relation between diuretic agents and aldoste- rone in cardiac and cirrhotic patients with sodium retention. Br. Med. J., 1:1134. With P. S. Chen, fir., and I. H. Mills. Ultrafiltration studies of steroid-protein binding. I. Endocrinol., 23:129. With A. G. T. Casper, C. S. Delea, and I. D. H. Slater. On the role of the kidney in control of adrenal steroid production. Metab- olism, 10: 1006. With I. Steinfeld, T. Waldmann, and C. S. Delea. Metabolism of infused serum albumin in the hypoproteinemia of gastrointes- tinal protein loss and in analbuminemia. Trans. Assoc. Am. Physicians, 74:180. With J. P. Thomas. Blood volume measurements in normal subjects and in patients with cirrhosis or cardiac disease. Clin. Sci., 21:301.

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FREDERIC C. BARTTER 17 1962 With P. Fourman. The different effects of aldosterone-like steroids and hydrocortisone-like steroids on urinary excretion of potas- sium and acid. Metabolism, 11 :6. With N. M. Kaplan. The effect of ACTH, renin, angiotensin II and various precursors on biosynthesis of aldosterone by adrenal slices. }. Clin. Invest., 41:715. With I. R. Gill, Jr., and D. S. Gann. Restoration of water diuresis in Addisonian patients by expansion of the volume of extracel- lular fluid. I. Clin. Invest., 41: 1078. With P. Pronove, I. R. Gill, fir., R. C. MacCardle, and E. Diller. Hyperplasia of the juxtaglomerular complex with hyperaldos- teronism and hypokalemic alkalosis. Am. I. Med., 33:811. With D. S. Gann, I. F. Cruz, and A. G. T. Casper. Mechanism by which potassium increases aldosterone secretion in the dog. Am. I. Physiol., 202:991. 1963 With R. I. Henkin and I. R. Gill, fir. Studies on taste thresholds in normal man and in patients with adrenal cortical insufficiency: The role of adrenal cortical steroids and of serum sodium con- centration. I. Clin. Invest., 42: 727. With N. H. Bell and E. S. Gerard. Pseudohypoparathyroidism with osteitis fibrosa cystica and impaired absorption of calcium. I. Clin. Endocrinol., 23:759. With I. D. H. Slater, B. H. Barbour, H. Henderson, and A. G. T. Casper. Influence of the pituitary and the renin-angiotensin system on the secretion of aldosterone, cortisol and corticoster- one. I. Clin. Invest., 42:1504. 1964 With N. H. Bell and H. Schedl. An explanation for abnormal water retention and hypoosmolality in congestive heart failure. Am J. Med., 36:351. With N. H. Bell and J. R. Gill, Jr. On the abnormal calcium absorp- tion in sarcoidosis. Am. l. Med., 36:500. With I. R. Gill, Jr., B. H. Barbour, and I. D. H. Slater. Effect of angiotensin II on urinary dilution in normal man. Am I. Phys- iol., 206:750.

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18 BIOGRAPHICAL MEMOIRS With I. R. Gill, Jr., I. M. George, and A. Solomon. Hyperaldoster- onism and renal sodium loss reversed by drug treatment for malignant hypertension. N. Engl. J. Med., 270: 1088. With G. T. Bryan, B. Kliman, and I. R. Gill, Jr. Effect of human renin on aldosterone secretion rate in normal man and in pa- tients with the syndrome of hyperaldosteronism, juxtaglome- rular hyperplasia and normal blood pressure. J. Clin. Endocri- nol., 24:729. With D. Hellman and R. Baird. Relationship of maximal tubular reabsorption to filtration rate in the dog. Am. l. Physiol., 207:89. With D. S. Gann, C. S. Delea, I. R. Gill, fir., and }. P. Thomas. Control of aldosterone secretion by change of body potassium in normal man. Am. I. Physiol., 207:104. 1965 With I. D. H. Slater, B. H. Barbour, H. H. Henderson, and A. G. T. Casper. Physiological influence of the kidney on the secretion of aldosterone, corticosterone and cortisol by the adrenal cor- tex. Clin. Sci., 28:219. With G. T. Bryan and B. Kliman. Impaired aldosterone production in "salt-losing" congenital adrenal hyperplasia. J. Clin. Invest., 44:957. With Y. H. Pitch and W. S. Kiser. A case of villous adenoma of the rectum with hyperaldosteronism and unusual renal manifesta- tions. Am. J. Med., 39:483. With D. E. Hellman and W. Y. W. Au. Evidence for a direct effect of parathyroid hormone on urinary acidification. Am. I. Phys- iol., 209:643. With R. L. Ney, W. Y. W. Au, G. Kelly, and I. Radde. Actions of parathyroid hormone in the vitamin D-deficient dog. l. Clin. Invest., 44:2003. With G. T. Bryan and R. C. MacCardle. Hyperaldosteronism, hy- perplasia of the juxtaglomerular complex, normal blood pres- sure, and dwarfism: Report of a case. Pediatrics, 37:43. 1966 With I. R. Gill, fir. Adrenergic nervous system in sodium metabo- lism. II. Effects of guanethidine on the renal response to so- dium deprivation in normal man. N. Engl. J. Med., 275: 1466.

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FREDERIC C. BARTTER 1967 19 With J. R. Gill, Jr., A. A. Carr, L. E. Fleischmann, and A. G. T. Casper. Effects of pentolinium on sodium excretion in dogs with constriction of the vena cave. Am. J. Physiol., 212: 191. With J. R. Gill, Jr., and N. H. Bell. Effect of parathyroid extract on magnesium excretion in man.J. Appl. Physiol., 22:136. With R. A. Melick, J. R. Gill, Jr., S. A. Berson, R. S. Yalow, J. T. Potts, and G. D. Aurbach. Antibodies and clinical resistance to parathyroid hormone. N. Engl. J. Med., 276:144. With R. I. Henkin, R. E. McGlond, and R. Daly. Studies on auditory thresholds in normal man and in patients with adrenal cortical steroids. J. Clin. Invest., 46:429. With W. W. Davis, H. H. Newsome, L. D. Wright, W. G. Hammond, and J. Easton. Bilateral adrenal hyperplasia as a cause of pri- mary aldosteronism with hypertension, hypokalemia and sup- pressed renin activity. Am. J. Med., 42:642. With C. Y. C. Pak. Ionic interaction with bone mineral. I. Evidence for an isotonic calcium exchange with hydroxyapatite. Biochim. Biophys. Acta, 141:401. 1968 With M. Lotz and E. Zisman. Evidence of a phosphorus-depletion syndrome in man. N. Engl. J. Med., 278:409. With R. L. Ney and G. Kelly. Actions of vitamin D independent of parathyroid glands. Endocrinology, 82:760. With W. W. Davis, L. R. Burwell, and A. G. T. Casper. Sites of action of sodium depletion on aldosterone biosynthesis in the dog. }. Clin. Invest., 47:1425. With R. I. Henkin and G. T. Bryan. Aldosterone hypersecretion in non-salt-losing congenital adrenal hyperplasia. J. Clin. Invest., 47: 1742. With J. M. George and L. Gillespie. Aldosterone secretion in hy- pertension. Ann. Intern. Med., 69:693. With C. Y. C. Pak, M. R. Wills, and G. W. Smith. Treatment with thyrocalcitonin of the hypercalcemia of parathyroid carcinoma. J. Clin. Endocrinol., 28:1657. With G. S. Stokes, l. T. Potts, Tr., and M. Lotz. Mechanisms of action of d-Penicillamine and n-Acetyl-d-penicillamine in the therapy of cystinuria. Clin. Sci., 35:467.

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20 BIOGRAPHICAL MEMOIRS With R. i. Wurtzman, A. G. T. Casper, and L. A. Pohorecky. Im- paired secretion of epinephrine in response to insulin among hypophysectomized dogs. Proc. Natl. Acad. Sci. USA, 61:522. With R. D. Gordon, I. Spinks, A. Dulmanis, B. Hudson, and F. Halberg. Amplitude and phase relations of several circadian rhythms in human plasma and urine: Demonstration of rhythm for tetrahydrocortisol and tetrahydrocorticosterone. Clin. Sci., 35:307. 1969 With W. W. Davis and L. R. Burwell. Inhibition of the effects of angiotensin II on adrenal steroid production by dietary so- dium. Proc. Natl. Acad. Sci. USA, 63:718. With M. R. Wills, C. Y. C. Pak, and W. G. Hammond. Normocal- cemic primary hyperparathyroidism. Am. I. Med., 47:384. With M. R. Wills and I. R. Gill, fir. The interrelationships of sodium and calcium excretion. Clin. Sci., 37:621 1970 With I. M. George, L. Wright, N. H. Bell, and R. Brown. The syndrome of primary aldosteronism. Am. l. Med., 48:343. With M. R. Wills, I. Wortsman, and C.- Y. C. Pak. The role of par- athyroid hormone in the gastro-intestinal absorption of cal- cium. Clin. Sci., 39:39. 1971 With A. P. Simpoulos, J. R. Marshall, and C. S. Delea. Studies on the deficiency of 21-hydroxylation in patients with congenital adrenal hyperplasia. I. Clin. Endocrinol. Metab., 32:438. With H. H. Newsome, Jr., and M. S. Kafka. Intrarenal blood flow in dogs with constriction of the inferior thoracic vena cave. Am. J. Physiol., 221:48. With I. R. Gill, Jr., and C. S. Delea. A role for sodium-retaining steroid in the regulation of proximal tubular sodium reabsorp- tion in man. Clin. Sci., 42:423. With I. B. Transbol, J. R. Gill, Jr., M. Lifschitz, and C. S. Delea. Intestinal absorption and renal excretion of calcium in meta- bolic acidosis and alkalosis. Acta Endocrinol. (suppl.) (Copen- hagen), 155:217.

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FREDERIC C. BARTTER 21 1972 With I. R. Gill, Jr., and T. A. Waldmann. Idiopathic edema. I. The occurrence of hypoalbuminemia and abnormal albumin metab- olism in women with unexplained edema. Am. l. Med., 52:445. With I. R. Gill, fir., I. W. Cox, and C. S. Delea. Idiopathic edema. II. Pathogenesis of edema in patients with hypoalbuminemia. Am. I. Med., 52:452. With C. Y. C. Pak, D. A. East, L. H. Sanzenbacher, and C. S. Delea. Gastrointestinal calcium absorption in nephrolithiasis. I. Clin. Endocrinol. Metab., 35:261. 1973 With S. Middler, C. Y. C. Pak, and F. Murad. Thiazide diuretics and calcium metabolism. Metabolism, 22: 139. With I. B. Gross. Effects of prostaglandins, E,, Al, and F20` on renal handling of salt and water. Am. I. Physiol., 225:218. With L. A. Pohoreck, B. S. Baliga, and R. I. Wurtzman. Adreno- cortical control of catecholamine metabolism in the dog adrenal medulla: Relationship to protein synthesis. Endocrinology, 93:566. 1974 With C. Y. C. Pak and C. S. Delea. Successful treatment of recur- rent nephrolithiasis (calcium stones) with cellulose phosphate. N. Engl. J. Med., 290: 175. With W. L. Miller and W. I. Meyer III. Intermittent hyperphospha- temia, polyuria, and seizures new familial disorder. J. Pediatr., 86:233. 1975 With I. Walton and M. Dominguez. Effects of calcium infusions in patients with postmenopausal osteoporosis. Metabolism, 24:849. With H. Zimbler, G. L. Robertson, C. S. Delea, and T. Pomeroy. Ewing's sarcoma as a cause of the syndrome of inappropriate secretion of antidiuretic hormone. I. Clin. Endocrinol. Metab., 41:390. With B. Stripp, A. A. Taylor, J. R. Gillette, D. L. Loriaux, R. Easley,

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22 BIOGRAPHICAL MEMOIRS and R. H. Menard. Effect of spironolactone on sex hormones in man. }. Clin. Endocrinol. Metab., 41:777. 1976 With R. H. Menard and I. R. Gillette. Spironolactone and cyto- chrome P-450: Impairment of steroid 21-hydroxylation in the adrenal cortex. Arch. Biochim. Biophys., 173:395. With I. R. Gill, I. C. Frolich, R. E. Bowden, A. A. Taylor, H. R. Keiser, et al. Bartter's syndrome: A disorder characterized by high urinary prostaglandins and a dependence of hyperreni- nemia on prostaglandin synthesis. Am. }. Med., 61 :43. With C. E. Becker, T. G. Tong, U. Boerner, R. L. Roe, R. A. T. Scott, and M. B. MacQuarrie. Diagnosis and treatment of amanita phalloides-type mushroom poisoning. West. J. Med., 125:100. With I. D. Baxter, M. Schambelan, D. T. Matulich, B. I. Spindler, and A. A. Taylor. Aldosterone receptors and the evaluation of plasma mineralocorticoid activity in normal and hypertensive states. I. Clin. Invest., 58:579. With W. I. Meyer III, E. C. Diller, and F. Halberg. The circadian periodicity of urinary 17-ketosteroids, corticosteroids, and elec- trolytes in congenital adrenal hyperplasia. I. Clin. Endocrinol. Metab.,43:1122. 1977 With J. Yun, G. Kelly, and H. Smith, Jr. Role of prostaglandins in the control of renin secretion in the dog. Circ. Res., 40:459. With A. E. Broadus, I. E. Mahaffey, and R. M. Neer. Nephrogenous cyclic adenosine monophosphate as a parathyroid function test. I. Clin. Invest., 60:771. With N. Radfar, R. Easley, J. Kolins, N. {avadpour, and R. I. Sher- ins. Evidence for endogenous LH suppression in a man with bilateral testicular tumors and congenital adrenal hyperplasia. |. Clin. Endocrinol. Metab., 45:1194. 1978 With A. E. Broadus and L. J. Deftos. Effects of the intravenous administration of calcium on nephrogenous cyclic AMP: Use as a parathyroid suppression test. J. Clin. Endocrinol. Metab., 46:477.

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FREDERIC C. BARTTER 23 With A. E. Broadus and M. Dominguez. Pathophysiological studies in idiopathic hypercalciuria: Use of an oral calcium tolerance test to characterize distinctive hypercalciuric subgroups. J. Clin. Endocrinol. Metab., 47:751. With J. M. Vinci, J. R. Gill, R. E. Bowden, J. J. Pisano, J. L. Izzo, et al. The Kallikrein-kinin system in Bartter's syndrome and its response to prostaglandin synthetase inhibition. J. Clin. Invest., 61:1671. 1979 With M. S. Kafka, C. R. Lake, H. G. Gullner, J. F. Tallman, and T. Fujita. Adrenergic receptor function is different in male and female patients with essential hypertension. Clin. Exp. Hyper- tens., 1:613. With A. A. Licata, E. Bou, and J. Cox. Effects of dietary protein on urinary calcium in normal subjects and in patients with neph- rolithiasis. Metabolism, 28:895. With H. G. Gullner, C. R. Lake, and M. S. Kafka. Effect on inhi- bition of prostaglandin synthesis on sympathetic nervous sys- tem function in man. J. Clin. Endocrinol. Metab., 49:552. With H. G. Gullner, C. Cerletti, J. B. Smith, and J. R. Gill. Prosta- cyclin overproduction in Bartter's syndrome. Lancet, 2:767. ~ ~ ~ ~ . 1980 With H. G. Gullner, J. R. Gill, Jr., R. Lake, and D. J. Lakatua. Correction of increased sympathoadrenal activity in Bartter's syndrome by inhibition of prostaglandin synthesis. J. Clin. En- docrinol. Metab., 50:857. With T. Fujita, W. L. Henry, C. R. Lake, C. S. Delea. Factors influ- encing blood pressure in salt-sensitive patients with hyperten- sion. Am. J. Med., 69:334. With H. G. Gullner, J. R. Gill, Jr., and R. Dusing. The role of the prostaglandin system in the regulation of renal function in nor- mal women. Am. J. Med., 69:7 18. 1981 With C. M. Chan. Weight reduction: Renal mineral and hormonal excretion during semistarvation in obese patients. J. Am. Med. Assoc., 245:37 1. With S. Broder, T. R. Callihan, E. S. Jaffe, V. T. DeVita, W. Strober,

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24 BIOGRAPHICAL MEMOIRS and T. A. Waldmann. Resolution of longstanding protein-losing enteropathy in a patient with intestinal lymphangiectasia after treatment for malignant lymphoma. Gastroenterology, 80:166. With C. R. Lake, H. G. Gullner, R. J. Polinsky, M. H. Evert, and M. G. Ziegler. Essential hypertension: Central and Peripheral nor- eninenhrine. Science. 211:955. 1 ~ With H. G. Gullner and J. R. Gill. Correction of hypokalemia by magnesium repletion in familial hypokalemic alkalosis with tub- ulopathy. Am. J. Med., 71:578. With J. R. Gill. Overproduction of sodium-retaining steroids by the zone glomerulosa is adrenocorticotropin-dependent and me- diates hypertension in dexamethasone-suppressible aldosteron- ism. }. Clin. Endocrinol. Metab., 53:331. 1982 With H. G. Gullner, W. E. Nicholson, M. G. Wilson, and D. N. Orth. The response of plasma immunoreactive adrenocorticotropin, beta-endorphin/beta-lipotropin, gamma-lipotropin and cortisol to experimentally induced pain in normal subjects. Clin. Sci., 63:397. With N. C. Lan, B. Graham, and I. D. Baxter. Binding of steroids to mineralocorticoid receptors: Implications for in viva occu- pancy by glucocorticoids. I. Clin. Endocrinol. Metab., 54:332.

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