Reminiscence of a 50-year Adventure

Abstract

It began as a freshman medical student in 1944 at Washington University in St. Louis. Dr. Ronzoni, who ran the biochemistry course, was always on the lookout for students with an interest and talent in biochemistry. She sent me to Dr. Alexis F. Hartmann Sr, who put me to work, directed my interest toward pediatrics, and proved a magnetic and inspirational mentor. Measuring the utilization of “corn glycogen” in sick infants was my first exposure to carbohydrate metabolism. Then, with Drs. Hartmann and JV Cooke, we worked out the pathogenesis of “well water” methemoglobinemia that appeared in the Journal of Pediatrics in 1947. During residency at St. Louis Children’s, whenever I had a month’s rotation on child psychiatry, “the chief” would send me to a basic science lab to learn either a micromethod for measuring tocopherol (vitamin E) with Dr. Lowery in pharmacology or a technique for measuring insulin in plasma utilizing glucose uptake by the hypophysectomized rat diaphragm with Drs. C.R. Park and Carl F. Cori. A National Institutes of Health postdoctoral fellowship with Prof. Cori studying glucose uptake by the rat diaphragm under a variety of controlled variable conditions resulted in two publications in the Journal of Biological Chemistry.For 2 years during the Korean War, I was in the Army Chemical Corp and did research at the Army Chemical Center in Edgewood, Maryland, studying phosphorylase activation by epinephrine and glucagon in rabbit liver. A position with Dr. Harry Gordon in Baltimore provided me the opportunity to begin studies of glucose metabolism in neonates. As he stated it: “Nitowsky, you’re vitamin E and Cornblath, you are sugar.” We soon acquired lots of data about infants of diabetic mothers, glucagon responses in the first hours of life, and the impact of labor and cesarean section on those responses, but with no disease in sight. Then, while in 50% private practice, I consulted on six neonates within 10 months who had transient symptomatic neonatal hypoglycemia born to mothers with toxemia of pregnancy. This clinical entity seemed to follow me to Chicago in 1959 when I left private practice to take a full time job at Michael Reese in Chicago. There, the unique environment in the Hess Premature Nursery run by Evelyn Lundeen provided the inspiration and interest that stimulated our many studies on carbohydrate metabolism in infancy (I through X published over the years in Pediatrics).Dr. Robert Schwartz from Cleveland reviewed all of my papers, and I reviewed all of his. I would suggest revisions and offer criticisms that he would ignore and vice versa. So, in 1963, when I was asked by Dr. Buck Schaffer to write about neonatal hypoglycemia in his newborn monograph series, it was only natural that I would ask Bob to be coauthor. Thus began a most wonderful, profitable, and compatible collaboration that has survived over 40 years. The results were the three editions of Disorders of Carbohydrate Metabolism in Infancy as well as many collaborative and independent studies published in a variety of peer-reviewed medical journals. Just a historical note in passing, Dr. Schaffer was a full time practitioner who originated the term “neonatology” to describe the subspecialty area.In 1965, the first international meeting to discuss neonatal hypoglycemia and carbohydrate metabolism in infants was held in Tokyo. This was the first major attempt to define and characterize neonatal hypoglycemia. Some 30 years later, a follow-up meeting was held in Kobe, Japan, in 1995. While progress had been impressive and new knowledge was immense, controversy still remained about definitions of significantly low blood glucoses and neurological outcome.And so it went, from Michael Reese (1959 through 1961) to University of Illinois and Cook County Hospital (1961 through 1968) and back to Baltimore as Chairman of Pediatrics at University of Maryland School of Medicine from 1968 through 1978 and then special assistant to Jim Sidbury, the Scientific Director of NICHD 1978 through 1983.While at NIH, I had to make a decision about research interests and further areas of pediatrics to which I might devote my efforts and time. Any thoughts about leaving the area of hypoglycemia and carbohydrate metabolism were abruptly aborted in 1981 when my wife of 33 years developed an islet cell tumor and symptomatic hypoglycemia. No one would believe her, or me, until the tumor was demonstrated on ultrasonography, by a selective arteriogram, and finally removed surgically, resulting in a cure. My destiny was sealed! How could I even think about other areas of research? It has been hypoglycemia ever since.The ever-increasing blood glucose levels that have been reported to be hypoglycemic in the newborn provided the impetus for continuing to lecture, write, and review the field of neonatal hypoglycemia as well as the reason for this review.