A.McGehee Harvey

Systemic Lupus Erythematosus: Review Of The Literature And Clinical Analysis Of 138 Cases

The editor in his introduction admits that this Year Book will give the reader a picture of the pattern of pathology through his eyes. The picture is certainly very alive, and most of the subjects and papers chosen for inclusion are, as is to be expected, newer work and newer concepts arising in the past year. Most aspects of pathology find a corner, and if a busy pathologist wishes to obtain a quick paint-brush sketch of the years publication in pathology this book provides such a picture. Anyone interested in a particular subject will naturally not obtain satisfaction as this book is not intended to cater for the expert. I keep it as bedside reading, thus maintaining an interest in many aspects of pathological routine and research. A. GORDON SIGNY.

The serum alkaline phosphatase in chronic infiltrative disease of the liver

Abstract The diagnostic significance of an elevation of serum alkaline phosphatase in the presence of a normal serum bilirubin is discussed. Attention is called to a group of patients with chronic infiltrative disease of the liver due to sarcoid, tuberculosis, Hodgkins disease and other similar conditions in which this combination exists. Although less frequent than biliary obstruction, Pagets disease and metastatic carcinoma, these cases may present as diagnostic problems and knowledge of this chemical pattern may be helpful. Obstruction of the biliary duct should always be considered first when the serum alkaline phosphatase is found to be elevated as the therapeutic possibilities are brighter than in the case of any of the diseases under consideration herein.

Alterations in neuromuscular transmission in myasthenia gravis as determined by studies of drug action

Summary The injection of ACh was found to produce, in normal subjects and in patients with myasthenia gravis, transient stimulation of motor unit activity followed by prompt transient depression of induced potentials, attributable to the depolarizing action of ACh. In myasthenic patients this was followed by a period of transient potentiation of induced potentials. In both normal subjects and myasthenic patients there then ensued a late prolonged depression of induced potentials, attributable to choline released as a result of hydrolysis of ACh. This late depression has the properties of a depolarizing block in normal subjects and a competitive block in patients with myasthenia gravis. These observations indicate that the defect in neuromuscular transmission in myasthenia gravis may be due to a competitive (ACh inhibitory) block produced by choline released in a normal manner during neuromuscular transmission following hydrolysis of endogenous ACh.

Electromyographic changes in myasthenia gravis

Summary The partial block of transmission at the neuromuscular junction in generalized myasthenia gravis manifests several characteristic features. 1. There is a slight degree of block to the passage of a single impulse. 2. Following the passage of a single impulse there is an increase in the degree of block which reaches a maximum about one second after the passage of the impulse. Ten seconds may be required before the degree of block decreases to its initial level. 3. The application of a train of impulses to the neuromuscular junction results first in a progressive increase in block to the passage of the impulses. This is followed by a transient decrease in block which in turn is followed by a progressive increase in degree of block. The magnitude of this increase in block increases as the stimulating frequency is raised. 4. Repetitive nerve stimulation is followed after a brief interval by a period of facilitation of neuromuscular transmission. This post-tetanic facilitation represents a decrease in the myasthenic block and is probably prejunctional in origin. The degree of post-tetanic facilitation is increased by increasing the duration or frequency of the tetanic stimulation. The post-tetanic facilitation of transmission of a single impulse is at the expense of the myasthenic subjects ability to transmit subsequent impulses. While such a study provides no direct evidence regarding the cause of the myasthenic block, it does afford a detailed description of this block. Such a description provides a basis upon which comparisons can be made between the myasthenic block and pharmacologically produced blocks; it gives a frame of reference against which drug-produced changes in the myasthenic block may be measured. The close resemblance between the neuromuscular block in myasthenia gravis and the block produced by d-tubocurarine in normal subjects has been pointed out. This indicates that the myasthenic block could be produced by a competitive (or curare-like) block.

Classics in Clinical Science: The Concept of Renal Clearance

A major share of the advances in medical knowledge has come about through the work of clinical investigators who applied the methods of science to the study of disease. Their skill in identifying important problems at the bedside and constructing practical solutions which enlarged the scientific base of medical practice, has resulted in tremendous advances in the armamentarium of every physician. In the climate of today, when the clinician eagerly utilizes the methods of the laboratory, it is difficult to believe that early in this century clinicians looked with suspicion upon newfangled things and basic scientists had disdain for research carried out by clinicians. This earlier attitude of clinicians is typified by the story told David L. Edsall by President Eliot of Harvard. Mr. Eliot had forced through the faculty of the Harvard Medical School the establishment of a course on bacteriology and the appointment of Dr. H. C. Ernst, who had recently returned from study in Europe, as the teacher of the subject. There had been violent opposition to the establishment of a course in so new a subject of questionable value and a professor of pediatrics had been especially violent in opposition. Methods for demonstration of the diphtheria bacillus were already available for diagnosis, and soon after Ernst’s appointment the use of diphtheria antitoxin was introduced. Dr. Ernst was the only man in the city who knew how to recognize the bacillus or to make an antitoxin. One day Mr. Eliot met the professor of pediatrics coming from Dr. Ernst’s laboratory, and said to him: “Doctor, isn’t this an odd place for you to be?” He replied: “Yes, but nowadays one has to come here for a diagnosis and now we have to come here for our treatment.” This attitude continued in some degree, however, for long afterwards. When Edsall went to Harvard as Jackson Professor of Medicine in 1912 Mr. Lowell, who had been president of Harvard University for three years, told him that at faculty meetings the clinicians sat on one side of the table, the laboratory men on the other, and each opposed the other in everything. A physician-scientist who was equally at home at the bedside and at the laboratory bench was Thomas Addis [l]. Born in Edinburgh in 1881, he came to this country in 1911 to take over the clinical laboratory at Stanford under Ray Lyman Wilbur. Addis’ genius for research soon led him to cast off the burdens of the routine laboratory and within a short time his important studies on the kidney were launched. In collaboration with various associates, his investigations of renal disease brought a continual output of excellent work until his retirement in 1948. He first studied the physiology of the kidney but soon embarked on investigations of disordered structure and function in Bright’s disease. Addis and others at Stanford were stationed at Camp Lewis, Washington, during World War I. While there they made important observations on blood pressure and pulse rate, similar to those made by Horace Smirk on basal blood pressure many years later. It was after his return to Stanford at the end of the war that Addis began his investigations into urinalysis and renal function. One of his classic contributions appeared in the first issue of the Journal of Urology in 1917 [2] entitled “The Ratio Between the Urea Content of the Urine and of the Blood After the Administration of Large Quantities of Urea. An Approximate Index of the Quantity of Actively Functioning Kidney Tissue.” This paper began with a penetrating review of the previous work on the testing of renal function and then was followed with Addis’ own rationale for developing the “urea ratio “: “the ratio between the urea content of the urine and of the blood (UV: B) expresses the number of times by which the urea excreted in the urine during a certain period of time exceeds the amount of urea present in 100 cc of blood supplied to the kidney during

Classics in clinical science: James L. Gamble and “gamblegrams”

James Lawder Gamble (1883-1959) one of the most important contributors to the advance of clinical science in this country, graduated from the Harvard Medical School in 1910. Following a two-year medical internship at the Massachusetts General Hospital and a year on the staff at the Children’s Hospital in Boston, he visited various European clinics. His sojourn in Europe represented a turning point in his career, as he developed an interest in the study of disease by the quantitative methods of biochemistry, cumbersome as they were at that time [l-3]. On his return to Boston, Gamble worked for a brief period in the laboratory of Otto Folin, professor of biochemistry at Harvard, where simple chemical procedures applicable to the study of metabolic processes in man were being developed. He then returned to the Massachusetts General Hospital as an investigator in the small chemical laboratory under the direction of Fritz Talbot. While there, he formed an enduring friendship with his Harvard classmate Walter W. Palmer, who later became Professor of Medicine at Columbia’s College of Physicians and Surgeons in New York. Gamble fell under the spell of Professor Lawrence J. Henderson, with whom Palmer was working; he was fascinated by Henderson’s physicochemical approach to physiologic processes. In accepting the Kober Medal of the Association of American Physicians in 1951, Gamble [4] spoke as follows regarding the importance of these early influences on his career: “In 1913 the gentle and kindly Folin gave me headspace . . . and I found it an exciting experience to learn these new technics which made quantitative information so easy to come by. . . I had a great affection for Van Slyke’s first CO2 burette. It was not the large machine of nowadays with the noisy mechanical shaker. One rocked it gently by hand as a little girl does her doll. . . “On leaving Folin’s laboratory my luck continued. In a small chemistry laboratory at the MGH my classmate Bill Palmer was measuring pH in the urine for the first time and carrying out under Lawrence Henderson’s guidance their classic description of the process of acid excretion . . . Henderson appeared about twice a week to see how Bill was getting along. It was evident that he did not like the clatter that I made dashing about the Laboratory tending my various analyses and one day he came over, placed his hand on my shoulder and said: ‘Young man, you will never get anywhere in this game until you learn an attitude of leisure.’ From then on he took the kindliest interest in my endeavor in a direction for which I was so ill prepared. Although I never worked directly with Henderson I learned from him to admire the beauty of the physico-chemical systems which sustain the body fluids, the marvel of their automaticity and their remarkable resiliency in the presence of obstacles imposed by disease, and ever since I have been content to work in this field as a humble artisan applying the simple tool of quantitative description to the pattern provided by this great architect of concept. Lawrence Henderson’s friendliness, which came to me by sheer accident, I count as one of fortune’s largest gifts.” In 1915, Gamble was invited to become a staff member in the new full-time department of pediatrics under John Howland at the Johns Hopkins University School of Medicine. He remained in Baltimore until 1922 when he was recruited by Oscar Schloss to join him in the establishment of a full-time staff in the department of pediatrics at the Harvard Medical School. Schloss left Boston within a year to return to New York, but fortu-