Archives of Internal Medicine

Roland, Charles G.

doi: 10.1001/archinte.1971.00310160013001pmid: N/A

Abstract The patient feels very sick. He is tired and apprehensive, his heart pounds and his breathing is labored. From time to time he is overcome by fright and the conviction that he is seriously ill or even about to die. Still, his doctor says: "There is nothing wrong with you." This is a description of someone with an anxiety neurosis, a chronic disorder that affects perhaps 5 percent of the U.S. population. Most physicians have been unable to recognize it, let alone treat it; its cause has seemed to be obscure and somehow "psychogenic." Yet in our laboratory at the Washington University School of Medicine we have been able to produce the symptoms of anxiety neurosis and even acute anxiety attacks in susceptible patients by chemical means: we administer enough lactate, a normal product of cell metabolism, to raise the blood lactate level about as high as it is in

doi: 10.1001/archinte.1971.00310160019002pmid: N/A

This article is only available in the PDF format. Download the PDF to view the article, as well as its associated figures and tables. Abstract Cardiogenic shock Intra-aortic counterpulsation appears to be the method of choice for treating patients in cardiogenic shock, according to a comparative study at St. Vincent's Hospital and Medical Center, New York.Hiltrud Mueller, MD, chief of the hospital's Shock Unit, and her colleagues studied the effects of intraaortic counterpulsation (IACP), L-norepinephrine and isoproteronol in 22 patients treated over a six-month period.The team's conclusions, as reported to the American College of Cardiology meeting at Washington: Isoproteronol therapy in six patients led to increased cardiac output and coronary blood flow. At the same time, the myocardial metabolism of the patients deteriorated, apparently because the increased work load of the heart with its attendant demands for oxygen exceeded the increases of perfusion and oxygenation given by the drug. The effects of L-norepinephrine were studied in eight patients. This agent resulted in an increase of coronary blood flow, myocardial metabolism and myocardial work,

M.D.B.,

doi: 10.1001/archinte.1971.00310160047003pmid: N/A

This article is only available in the PDF format. Download the PDF to view the article, as well as its associated figures and tables. Abstract The readers of the Archives of Internal Medicine who did not know John Bamber Hickam personally may not fully appreciate why an entire issue of The Archives has been designed as a scientific memorial to him. It is the intent of this note to share our appreciation of him as a friend and teacher so that the articles which have been collected in this symposium will be read with an interest in the work of the man as well as of the discipline. There are also many readers of The ARCHIVES whose professional careers in active practice may not have led them to be familiar with the details of academic medicine; for them, John's career is recounted at some length. The first impression that John evoked when you met him in his office, on the wards, at scientific meetings, in his laboratory, or in his home was one of cheerfulness,

Investigator, ;Ross, Joseph C.

doi: 10.1001/archinte.1971.00310160049004pmid: N/A

Abstract This issue of The Archives has been dedicated as a memorial volume to John B. Hickam, MD. Anyone who was closely associated with him or who has evaluated his accomplishments knows that he demonstrated qualities of excellence as a physician, left behind clearly visible evidences of his role as an educator, and made important contributions as an investigator. His research was important, not only in advancing knowledge, but also as a springboard for the development of the careers of numerous other physicians, educators, and investigators. One group of papers in this volume exemplifies his own research while the other group, composed of ten original papers, represent the work of some of his former associates. One of the papers was written by Eugene Stead, who had an important role in the development of his career. One or more authors of the other nine original papers are men and women in medicine

Bailey, Orville T.;Hickam, John B.

doi: 10.1001/archinte.1971.00310160052005pmid: N/A

Abstract MOST of the attention given to rupture of the chordae tendineae of the mitral valve has been accorded those instances which occur during the course of acute or subacute bacterial endocarditis, or which result from severe external violence to the chest. Frew1 described a case in which rupture of the mitral chordae tendineae took place during a prolonged attack of acute rheumatic fever; and Frothingham and Hass2 have reported an instance of spontaneous rupture of mitral chordae which were apparently not the site of previous disease. In the last 2,400 autopsies at the Peter Bent Brigham Hospital, there were eleven instances of rupture of the mitral chordae tendineae. Four were associated with bacterial endocarditis involving this valve. The other seven patients presented no evidence of bacterial endocarditis and no history of severe trauma to the chest, but the mitral valves and their chordae tendineae showed scarring, calcification, or References 1. Frew, H. W. O.: Rupture of the Chordae Tendineae Following Scarlet Fever , Glasgow M. J. 115: 195, 1931. 2. Frothingham, C., and Hass, G. M.: Rupture of Normal Chordae Tendineae of the Mitral Valve , Am. Heart J. 9: 492, 1934.Crossref 3. Wankel: Ein Fall von spontaner Papillarmuskelzerreissung , Dissertation , Giessen, 1911. 4. Quoted by Voigt, W.21 5. Wagner, H.: Beitrag zur spontanen Papillarmuskelruptur , Frankfurt. Ztschr. f. Path. 37: 293, 1929. 6. Jezler, A., and Finkeldey, W.: Spontaner Papillarmuskelabriss bei Koronarsklerose , Ztschr. f. Kreislaufforsch. 23: 377, 1931. 7. Fischer, B.: Völliger Abriss eines Papillarmuskels im linken Ventrikel durch Coronarsklerose , Klin. Wchnschr. 1: 991, 1922.Crossref 8. Dennig, A.: Ein Fall von Papillarmuskelzerreissung , Deutsches Arch. f. klin. Med. 96: 163, 1909. 9. Glendy, R. E., and White, P. D.: Nonpenetrating Wound of Heart; Rupture of Papillary Muscle and Contusion of Heart Resulting From External Violence , Am. Heart J. 11: 366, 1936.Crossref 10. von Albertini, A. V.: Ein Gutachten über eine traumatische Sehnenfadenzerreissung der Mitralis mit tödlicher Mitralinsuffizienz , Schweiz. med. Wchnschr. 68: 861, 1938. 11. Vaquez, H.: Diseases of the Heart. Translated by Laidlaw, Philadelphia, 1924, W. B. Saunders Co. 12. Stern, R.: Traumatische Entstehung innerer Krankheiten , Jena, 1930, Gustav 'Fischer. 13. Quoted by von Albertini, A. V.9 14. Bellet, S., Gouley, B., Nichols, C. F., and McMillan, T. M.: Loud Musical Diastolic Murmurs of Aortic Insufficiency. Clinical and Pathologic Observations Upon Their Cause and the Mechanism of Their Production , Am. Heart J. 18: 483, 1939.Crossref 15. Spalding, E. D., and von Glahn, W. C.: Syphilitic Rupture of the Papillary Muscle of the Heart , Bull. Johns Hopkins Hosp. 32: 30, 1921. 16. Klein: Bratisl. lekár. listy 9: 777, 1929. 17. Quoted by Stevenson, R. R., and Turner, W. J.15 18. Stevenson, R. R., and Turner, W. J.: Rupture of a Papillary Muscle in the Heart as a Cause of Sudden Death , Bull. Johns Hopkins Hosp. 57: 235, 1935. 19. Hausen-Faure, G., and Hasenjäger, E.: Zwei Fälle von Papillarmuskelruptur , Klin. Wchnschr. 17: 540, 1938.Crossref 20. Moragues, V.: Spontaneous Rupture of a Papillary Muscle of the Heart , Am. Heart J. 17: 106, 1939.Crossref 21. Lowry, F. C., and Burn, C. G.: Spontaneous Rupture of the Posterior Papillary Muscle of the Heart , Arch. Path. 31: 382, 1941. 22. Teacher: Case of Rupture of a Papillary Muscle of the Left Ventricle of the Heart , Glasgow M. J. 75: 374, 1911. 23. Quoted by Voigt, W.21 24. von Glahn, W. C., and Horowitz, E. A.: Rupture of Papillary Muscle of the Heart , Proc. New York Path. Soc. 23: New Series, 103, 1923. 25. Voigt, W.: Spontanruptur eines Papillarmuskels, zugleich ein Beitrag zur Gestalt des linken hinteren Papillarmuskels , Ztschr. f. Kreislaufforsch. 24: 667, 1932. 26. Lipscomb, H. R.: Rupture of a Papillary Muscle in the Heart , M. Bull. Vet. Admin. 15: 73, 1938. 27. Sager, R. V.: Coronary Thrombosis; Perforation of the Infarcted Interventricular Septum , Arch. Int. Med. 53: 140. 1934.Crossref

HICKAM, JOHN B.;CARGILL, WALTER H.;GOLDEN, ABNER

doi: 10.1001/archinte.1971.00310160075006pmid: N/A

Abstract INTRODUCTION Emotional disturbances may have a profound effect on the circulation, causing changes in the heart rate, cardiac output (1 and 2), blood pressure, tone of peripheral vessels, and the electrocardiogram (3). This is particularly true of the emotional state which may develop in persons who find themselves in a hazardous situation. For present purposes this emotional state is termed "anxiety," although it is recognized that other reactions such as resentment or anger may also occur, depending upon the individual and the circumstances. In any study on unanesthetized human subjects, changes produced by anxiety may mask completely the physiologic or pharmacologic effects which are obvious in a relaxed subject. In the interpretation of experimental data. objective criteria by which it can be established, or even suspected, that anxiety is having an effect on cardiovascular function are useful. It is also of importance to clinical medicine to have further information concerning References 1. Stead, E. A., Jr., Warren, J. V., Merrill, A. J., and Brannon, E. S., The cardiac output in male subjects as measured by the technique of right atrial catheterization. Normal values with observations on the effect of anxiety and tilting. J. Clin. Invest. , 1945, 24, 326.Crossref 2. Wolf, G. A., Jr., and Wolff, H. G., Studies on the nature of certain symptoms associated with cardiovascular disorders. Psychosom. Med. , 1946, 8, 293.Crossref 3. Mainzer, F., and Krause, M., The influence of fear on the electrocardiogram. Brit. Heart J. , 1940, 2, 221.Crossref 4. Nickerson, J. L., Symposium on cardiac output; the low frequency, critically-damped ballistocardiograph. Federation Proc. , 1945, 4, 201. 5. Padilla, T., Cossio, P., and Berconsky, I., Sondeo del corazón; determinacion del volumen minuto circulatorio. Semana méd. , 1932, 2, 445. 6. Cournand, A., and Ranges, H. A., Catheterization of the right auricle in man. Proc. Soc. Exper. Biol. & Med. , 1941, 46, 462. 7. Aperia, A., Hemodynamical Studies, Skandinavisches Archiv für Physiologie , (Supplement 16) (to vol. 83), p. 35, 1940. 8. Hickam, J. B., and Cargill, W. H., Effect of exercise on cardiac output and pulmonary arterial pressure in normal persons and in patients with cardiovascular disease and pulmonary emphysema. J. Clin. Invest. , 1948, 27, 10. 9. Starr, I., Gamble, C. J., Margolies, A., Donal, J. S., Jr., Joseph, N., and Eagle, E., A clinical study of the action of 10 commonly used drugs on cardiac output, work and size; on respiration, on metabolic rate and on the electrocardiogram. J. Clin. Invest. , 1937, 16, 799. 10. Warren, J. V., Brannon, E. S., Stead, E. A., Jr., and Merrill, A. J., The effect of venesection and the pooling of blood in the extremities on the atrial pressure and cardiac output in normal subjects with observations on acute circulatory collapse in three instances. J. Clin. Invest. , 1945, 24, 337. 11. Lewis, T., Lecture on vasovagal syncope and the carotid sinus mechanism, with comments on Gowers' and Nothnagel's syndrome. Brit. Med. J. , 1932, 1, 873. 12. Starr, I., Ballistocardiographic studies of draftees rejected for neurocirculatory asthenia. War. Med. , 1944, 5, 155.

HICKAM, J. B.;FRAYSER, R.

doi: 10.1001/archinte.1971.00310160084007pmid: N/A

Abstract Gasometric methods for estimating blood oxygen are time-consuming. This consideration often limits the number of observations which can be made in the course of experiments requiring oxygen determinations. In many cases it is an arteriovenous difference which is particularly desired, as in the measurement of cardiac output by the Fick principle, or the estimation of oxygen consumption by human liver, kidney, or brain. The present paper describes a rapid, simple spectrophotometric method for determination of arteriovenous oxygen differences with an accuracy satisfactory for ordinary needs. The absolute oxygen content can also be estimated, subject to error caused by "inactive" hemoglobin. The method is based upon the principle that two well hemolyzed samples of blood drawn nearly simultaneously from the same individual will have substantially the same total hemoglobin content, "inactive" hemoglobin (1), turbidity, and content of other light-absorbing material; and that, consequently, the difference in optical densities of the two References 1. Ammundsen, E., and Trier, M., Acta med. Scand. , 101, 451 (1939).Crossref 2. Peters, J. P., and Van Slyke, D. D., Quantitative clinical chemistry; Methods , Baltimore, 321 (1932). 3. Drabkin, D. L., and Austin, J. H., J. Biol. Chem. , 112, 105 (1935-36). 4. Drabkin, D. L., and Schmidt, C. F., J. Biol. Chem. , 157, 69 (1945). 5. Hall, F. G., J. Physiol. , 80, 502 (1934). 6. Hall, F. G., J. Biol. Chem. , 130, 573 (1939). 7. Kramer, K., in Abderhalden, E., Handbuch der biologischen Arbeitsmethoden , Berlin and Vienna, Abt. V, Teil 8, 1083 (1935) 8. Brinkman and Wildschut (10). 9. Matthes, K., Arch. exp. Path. u. Pharmakol. , 176, 683 (1934).Crossref 10. Millikan, G. A., J. Physiol. , 79, 152 (1933). 11. Brinkman, R., and Wildschut, A. J. H., Acta med. Scand. , 94, 459 (1938).Crossref 12. Jonxis, J. H. P., Acta med. Scand. , 94, 467 (1938).Crossref 13. Von Issekutz, B., Jr., Arch. exp. Path. u. Pharmakol. , 197, 332 (1940-41).Crossref 14. Lowry, O. H., Smith, C. A., and Cohen, D. L., J. Biol. Chem. , 146, 519 (1942). 15. Groom, D., Wood, E. H., Burchell, H. B., and Parker, R. L., Proc. Staff Meetings Mayo Clin. , 23, 601 (1948). 16. Horecker, B. L., J. Biol. Chem. , 148, 173 (1943). 17. Drabkin, D. L., and Austin, J. H., J. Biol. Chem. , 112, 51 (1935-36). 18. McCarthy, E. F., and Van Slyke, D. D., J. Biol. Chem. , 128, 567 (1939). 19. Lange, H. F., Acta med. Scand. , (suppl.) 176 (1946).

HICKAM, J. B.

doi: 10.1001/archinte.1971.00310160093008pmid: N/A

Abstract In pulmonary disease the inspired air is often distributed unequally throughout the lung. The volume of the poorly aerated regions of the lung and their rate of ventilation are of importance to the clinician but quantitation of these values has been difficult. The situation was much clarified in 1950 by Robertson, Siri, and Jones (1) who demonstrated that an unequally ventilated lung behaves as though it consisted of a number of subdivisions of smaller size, each of which is homogeneously ventilated at its own particular rate. Preliminary work which led to the same concept was also reported at this time by Fowler, Cornish, and Kety (2). By continuously following the course of nitrogen elimination from the lungs of a subject breathing oxygen, it was possible to characterize these lung subdivisions in terms of size and ventilation rate. This information describes an unequally ventilated lung in a way which permits useful, References 1. Robertson, J. S., Siri, W. E., and Jones, H. B., Lung ventilation patterns determined by analysis of nitrogen elimination rates; use of the mass spectrometer as a continuous gas analyzer. J. Clin. Invest. , 1950, 29, 577.Crossref 2. Fowler, W. S., Cornish, E. R., Jr., and Kety, S. S., Measurement of alveolar ventilatory components. Am. J. Med. Sc. , 1950, N.S. 220, 112. 3. Standardization of definitions and symbols in respiratory physiology. Federation Proc. , 1950, 9, 602. 4. Jones, H. B., Respiratory system: Nitrogen elimination in Medical Physics , V. 2, Glasser, O., ed., Chicago, Year Book Publishers, Inc., 1950, p. 855. 5. Behnke, A. R., and Willmon, T. L., Gaseous nitrogen and helium elimination from the body during rest and exercise. Am. J. Physiol. , 1941, 131, 619. 6. Lawrence, J. H., Loomis, W. F., Tobias, C. A., and Turpin, F. H., Preliminary observations on the narcotic effect of xenon with a review of values for solubilities of gases in water and oils. J. Physiol. , 1946, 105, 197. 7. Fowler, W. S., Lung volumes in Methods in Medical Research , Vol. 2, Comroe, J. H., Jr., ed., Chicago, Year Book Publishers, Inc., 1950, p. 181. 8. Darling, R. C., Cournand, A., and Richards, D. W., Jr., Studies on the intrapulmonary mixture of gases. III. An open circuit method for measuring residual air. J. Clin. Invest. , 1940, 19, 609.Crossref 9. Cournand, A., Baldwin, E. DeF., Darling, R. C., and Richards, D. W., Jr., Studies on the intrapulmonary mixture of gases. IV. The significance of the pulmonary emptying rate and a simplified open circuit measurement of residual air. J. Clin. Invest. , 1941, 20, 681.Crossref 10. Gilson, J. C., and Hugh-Jones, P., The measurement of the total lung volume and the breathing capacity. Clin. Sc. , 1949, 7, 185. 11. Fowler, W. S., Cornish, E. R., Jr., and Kety, S. S., Lung function studies. VIII. Analysis of alveolar ventilation by pulmonary N2 clearance curves. J. Clin. Invest. , 1952, 31, 40.Crossref 12. Briscoe, W. A., Further studies on the intrapulmonary mixing of helium in normal and emphysematous subjects. Clin. Sc. , 1952, 11, 45.

Blair, E.;Hickam, J. B.

doi: 10.1001/archinte.1971.00310160103009pmid: N/A

Abstract Uneven mixing of gas within the lungs is characteristic of pulmonary emphysema. A number of technics have been devised to demonstrate unequal gas mixing in emphysema and to grade the severity of the defect. These have depended upon measuring various consequences of impaired mixing, such as delay in washing a test gas out of the lungs, delay in introducing a test gas into the lungs, or abnormally great variation in the concentration of expired gas during the course of a single breath. Recently it has become possible to describe defective intrapulmonary gas mixing in more complete terms. This has resulted from the finding that an unevenly ventilated lung behaves as if it consisted of several subdivisions, each evenly ventilated at its own rate.1,2 The volume and ventilation rate of these subdivisions can be measured, and these measurements provide a simple quantitative picture of the defect in intrapulmonary gas mixing. References 1. Robertson, J. S., Siri, W. E. and Jones, H. B. Lung ventilation patterns determined by analysis of nitrogen elimination rates; use of the mass spectrometer as a continuous gas analyzer. J. Clin. Investigation , 29: 577, 1950.Crossref 2. Fowler, W. S., Cornish, E. R., Jr. and Kety, S. S. Lung function studies. viii. Analysis of alveolar ventilation by pulmonary N2 clearance curves. J. Clin. Investigation , 31: 40, 1952.Crossref 3. Briscoe, W. A. Further studies on the intrapulmonary mixing of helium in normal and emphysematous subjects. Clin. Sc. , 11: 45, 1952. 4. Hickam, J. B., Blair, E. and Frayser, R. An open circuit helium method for measuring functional residual capacity and defective intrapulmonary gas mixing. J. Clin. Investigation , to be published. 5. Comroe, J. H., Jr. Methods in Medical Research , vol. 2. Chicago, 1950. The Year Book Publishers. 6. Baldwin, E. DeF., Cournand, A. and Richards, D. W., Jr. Pulmonary insufficiency. iii. A study of 122 cases of chronic pulmonary emphysema. Medicine , 28: 201, 1949.Crossref 7. Whitfield, A. G. W. Emphysema. Brit. M. J. , 2: 1227, 1952.Crossref 8. Roelsen, E. Fractional analysis of alveolar air after inspiration of hydrogen as a method for the determination of the distribution of inspired air in the lungs. Acta med. Scandinav. , 95: 452, 1938.Crossref 9. Roelsen, E. The composition of the alveolar air investigated by fractional sampling. Acta med. Scandinav. , 98: 141, 1939.Crossref 10. Marshall, R., Bates, D. V. and Christie, R. V. Fractional analysis of the alveolar air in emphysema. Clin. Sc. , 11: 297, 1952. 11. Hickam, J. B. Unpublished results.

SIEKER, HERBERT O.;HICKAM, JOHN B.

doi: 10.1001/archinte.1971.00310160115010pmid: N/A

Abstract INTRODUCTION Carbon dioxide intoxication is now recognized as a syndrome that can occur in persons with disorders which greatly reduce alveolar ventilation (3, 7, 13, 14, 33, 37, 42, 61, 63, 70, 79). The symptoms and clinical findings in this condition vary in character and severity and may simulate other disease entities. With moderate acidosis and hypercapnia, the patient may have no complaints, or the only symptoms noted may be weakness, lassitude, irritability, mild confusion, or headache. More severe respiratory acidosis can cause carbon dioxide narcosis with coma, respiratory depression and circulatory failure. Frequently, severe or prolonged narcosis results in the death of the patient.Retention of carbon dioxide is most commonly observed in individuals with chronic lung disease which results in impaired ventilation, particularly obstructive emphysema and pulmonary fibrosis. On this background carbon dioxide intoxication can develop when ventilation becomes mechanically more difficult; e.g., with a respiratory infection (67, References 1. Baldwin, E. deF., Cournand, A., and Richards, D. W., Jr.: Pulmonary insufficiency: study of 122 cases of chronic pulmonary emphysema. Medicine 28: 201,1949.Crossref 2. Barach, A. L.: Impairment in emotional control produced both by lowering and raising the oxygen pressure in the atmosphere. M. Clin. North America 28: 704,1944. 3. Barach, A. L.: Symposium on inhalational therapy; treatment of anoxia in clinical medicine. Bull. New York Acad. Med. 26: 370,1950. 4. Beecher, H. K., and Murphy, A. J.: Acidosis during thoracic surgery. J. Thoracic Surg. 19:50, 1950. 5. Beecher, H. K., Quinn, T. J., Jr., Bunker, J. P., D'Alessandro, G. L.: Effect of position and artificial ventilation on excretion of carbon dioxide during thoracic surgery. J. Thoracic Surg. 22: 135, 1951. 6. Blair, E., and Hickam, J. B.: Quantitative study of intrapulmonary gas mixing in emphysema. Am. J. Med. 18: 519,1955.Crossref 7. Boutourline-Young, H. J., and Whittenberger, J. L.: The use of artificial respiration in pulmonary emphysema accompanied by high carbon dioxide levels. J. Clin. Invest. 30:838, 1951.Crossref 8. Brown, C. C., Fry, D. L., and Ebert, R.: The mechanics of pulmonary ventilation in patients with heart disease. Am. J. Med. 17: 438, 1954.Crossref 9. Brown, E. W.: The physiological effects of high concentrations of carbon dioxide. U. S. Nav. M. Bull. 28: 721, 1930. 10. Burnum, J. F., Hickam, J. B., and McIntosh, H. D.: The effect of hypocapnia on arterial blood pressure. Circulation 9: 89, 1954.Crossref 11. Carroll, D.: Arterial blood oxygen and carbon dioxide tension studies in the respiratory paralysis of poliomyelitis. Bull. Johns Hopkins Hosp. 96: 242, 1955. 12. Christie, R. V.: Elastic properties of emphysematous lungs and their clinical significance. J. Clin. Invest. 13: 295, 1934.Crossref 13. Cohen, J. E., Carroll, D. G., and Riley, R. L.: Respiratory acidosis in patient with emphysema. Am. J. Med. 17: 447, 1954.Crossref 14. Comroe, J. H., Jr., Bahnson, E. R., and Coates, E. O., Jr.: Mental changes occurring in chronically anoxemic patients during oxygen therapy. J.A.M.A. 143: 1044, 1950.Crossref 15. Courville, C. B.: Asphyxia as consequence of nitrous oxide anesthesia. Medicine 15: 129, 1936. 16. Davies, C. E., and Mackinnon, J.: Neurological effects of oxygen in chronic cor pulmonale. Lancet 2: 883, 1949.Crossref 17. Dayman, H.: Mechanics of airflow in health and in emphysema. J. Clin. Invest. 30: 1175, 1951.Crossref 18. Deal, C. P., and Green, H. D.: Effects of pH on blood flow and peripheral resistance in muscular and cutaneous vascular beds in the hind limb of the pentabarbitalized dog. Circulation Res. 2: 148, 1953.Crossref 19. d'Elseaux, F. C., and Solomon, H C.: Use of carbon dioxide mixtures in stupors occurring in psychoses. Arch. Neurol. & Psychiat. 29: 213, 1933. 20. Donald, K. W.: Neurological effects of oxygen. Lancet 2: 1056, 1949. 21. Donald, K. W.: Acute respiratory insufficiency. Lancet 1: 495, 1953.Crossref 22. Donald, K. W., and Christie, R. V.: Respiratory response to carbon dioxide and anoxia in emphysema. Clin. Sc. 8: 33, 1949. 23. Donald, K. W., Renzetti, A., Riley, R. L., and Cournand, A.: Analysis of factors effecting concentrations of oxygen and carbon dioxide in gas and blood of lungs; results. J. Applied Physiol. 4: 497, 1952. 24. Drinker, C. K.: Pulmonary edema and inflammation . Harvard University Press, 1945. 25. Dripps, R. D., and Comroe, J H., Jr.: Respiratory and circulatory response of normal man to inhalation of 7.6 and 10.4 per cent CO2 with comparison of maximal ventilation produced by severe muscular exercise, inhalation of CO2 and maximal voluntary hyperventilation. Am. J. Physiol. 149: 43, 1947. 26. Ferrer, M. I., Harvey, R. M., Cathcart, R. T., Webster, G. A., Richards, D. W., Jr., and Cournand, A.: Some effects of digoxin upon heart and circulation in man; digoxin in chronic cor pulmonale. Circulation 1: 161, 1950.Crossref 27. Fishman, A. P., Samet, P., and Cournand, A.: Ventilatory drive in chronic pulmonary emphysema. Am. J. Med. 19: 533, 1955.Crossref 28. Harvey, R. M., Ferrer, M. I., and Cournand, A.: The treatment of chronic cor pulmonale. Circulation 7: 932, 1953.Crossref 29. Harvey, R. M., Ferrer, M. I., Richards, D. W., Jr., and Cournand, A.: Influence of chronic pulmonary disease on heart and circulation. Am. J. Med. 10: 719, 1951.Crossref 30. Hickam, J. B., and Frayser, R.: Spectrophotometric determination of blood oxygen. J. Biol. Chem. 180: 457, 1949. 31. Hickam, J. B., Pryor, W. W., Page, E. B., and Atwell, R. J.: Respiratory regulation during exercise in unconditioned subjects. J. Clin. Invest. 30: 503, 1951.Crossref 32. Hickam, J. B., Sieker, H. O., Pryor, W. W., and Frayser, R.: Use of the Seeler resuscitator in man . W. A. D. C. Tech. Report 55-165, Wright Air Development Center, March 1955. 33. Hickam, J. B., Sieker, H. O., Pryor, W. W., and Ryan, J. M.: Carbon dioxide retention during oxygen therapy. North Carolina M. J. 13: 35, 1952. 34. Kaplan, E., Detweiler, J., Kaplan, B. M., and Baker, L. A.: Respirator in chronic pulmonary disease with spondylitis and fixation of thorax. J. A. M. A. 156: 1499, 1954. 35. Kelman, H.: Observations in catatonia with mixtures of carbon dioxide and oxygen. Psychiatric Quart. 6: 513, 1932.Crossref 36. Lange, K., Craig, F., Tchentkoff, V., Aberman, J., and LaCosto, F.: Effects of experimental acidosis on dynamics of circulation. Am. J. M. Sc. 222: 61, 1951.Crossref 37. Lovejoy, F. W., Jr., Yu, P. N., Nye, R. E., Jr., Joos, H. A., and Simpson, J. H.: Pulmonary hypertension. III. Physiologic studies in three cases of carbon dioxide narcosis treated by artificial respiration. Am. J. Med. 16: 4, 1954.Crossref 38. Lukas, D. S.: Pulmonary function in group of young patients with bronchial asthma. J. Allergy 22: 411, 1951.Crossref 39. Marshall, R. and Christie, R. V.: The visco-elastic properties of the lungs in acute pneumonia. Clin. Sci. 13: 403, 1954. 40. Mead, J., Lindgren, I., and Gaensler, E. A.: The mechanical properties of the lungs in emphysema. J. Clin. Invest. 34: 1005, 1955.Crossref 41. Meduna, L. J.: Carbon Dioxide Therapy: A Neurophysiological Treatment of Nervous Disorders . Charles C. Thomas, Springfield, Ill., 1950. 42. Motley, H. L.: Symposium: pediatric aspects of inhalation therapy; the use of oxygen in comatose states. Bull. New York Acad. Med. 26: 479, 1950. 43. Motley, H. L., Cournand, A., Werko, L., Himmelstein, A., and Dresdale, P.: The influence of short periods of induced acute anoxia upon pulmonary artery pressures in man. Am. J. Physiol. 150: 315, 1947. 44. Patterson, J. L., Jr., Heyman, A., and Duke, T. W.: Cerebral circulation and metabolism in chronic pulmonary emphysema with observations on effects of inhalation of oxygen. Am. J. Med. 12: 382, 1952.Crossref 45. Peters, J. P., and Van Slyke, D. D.: Quantitative Clinical Chemistry . Vol. II. Methods. Williams & Wilkins, Baltimore, Md., 1932. 46. Pollock, G. H.: Central inhibitory effects of carbon dioxide; Felis domesticus. J. Neurophysiol. 12: 315, 1949. 47. Prime, F. J., and Westlake, E. K.: The respiratory response to CO2 in emphysema. Clin. Sci. 13: 321, 1954. 48. Pryor, W. W., Hickam, J. B., Page, E. B., and Sieker, H. O.: Factors influencing pulmonary compliance in heart disease. Am. J. Med. 19: 149, 1955.Crossref 49. Pryor, W. W., Marks, G., Sieker, H. O., Wendt, W., and Harmon, R. M.: Performance evaluation of Seeler resuscitator . W.A.D.C. Tech. Rep. 53-453, December 1953. 50. Rich, M. Scheinberg, P., and Belle, M. S.: Relationship between cerebrospinal fluid pressure changes and cerebral blood flow. 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