Showing papers in "Journal of Clinical Investigation in 1956"

A new method for measuring airway resistance in man using a body plethysmograph: values in normal subjects and in patients with respiratory disease

Abstract: Satisfactory methods, utilizing measurements of transthoracic or transpulmonary pressure and airflow, are now available for determining \"nonelastic\" pulmonary resistance. However, the nonelastic pulmonary resistance has two components, tissue resistance and airway resistance, and no valid direct method is available for measuring either of these components separately in man. Since airway resistance is the ratio of alveolar pressure during flow to airflow, airway resistance alone could be measured if there were a method for determining alveolar pressure during flow. This report presents a new method for accomplishing this measurement, and gives data for airway resistance obtained in normal subjects and in patients with respiratory disease. Of previous attempts to measure airway resistance, one of the earliest was the painstaking study by Rohrer (1) who made anatomical measurements on the tracheobronchial tree of a human lung post mortem and calculated the cumulative resistance to airflow of the entire system using Poiseuille's law and turbulence theory. The first important experimental study of pulmonary resistance in the living animal was made by von Neergaard and Wirz who, in 1927 (2), analyzed intrapleural pressure into two major components, \"dynamic\" (which is essentially resistive) and \"static\" (which is predominantly elastic in nature). This approach made it possible to obtain values for total pulmonary resistance, though not for airway resistance alone. Bayliss and Robertson (3), reasoning that airway resistance, but not tissue resistance, would vary with the viscosity of the gases breathed, ventilated isolated animal lungs with gases of different density and viscosity;

The quantitatively minor role of carbohydrate in oxidative metabolism by skeletal muscle in intact man in the basal state. Measurements of oxygen and glucose uptake and carbon dioxide and lactate production in the forearm.

Abstract: Skeletal muscle accounts for some 40 per cent of body weight. Presumably, by virtue of its bulk as the largest mass of tissue, its metabolism may be a major factor in total body economy and yet surprisingly little is known of the quantitative characteristics of metabolism of skeletal muscle. Studies of excised muscle and its extracts have provided a rich background relating to the metabolic capabilities of muscle. They have shown a great deal about the apparatus with which muscle is equipped to perform its functions in dissimilating metabolites but they fail to reveal the quantitative importance of particular pathways of dissimilation in the total scheme.

The metabolism of chylomicra. I. The removal of palmitic acid-1-C14 labeled chylomicra from dog plasma.

Abstract: It is now generally accepted that the intestinal lymphatics constitute the exclusive pathway for the absorption of long chain fatty acids, whether ingested unesterified or as glycerides. These fatty acids appear in the thoracic duct lymph as chylomicra. The subsequent fate of the absorbed fat has been explored very little, and the role of plasma lipoproteins in chylomicron transport and the sites of removal of the absorbed fat remain unknown. Approximately 95 per cent of long chain fatty acids appear in the lymph as triglycerides and 5 per cent as phospholipids (1). Bergstrom, Borgstrom, and Rottenberg (2) fed labeled stearic acid and tristearin to fasting rats. Over a period of 3 to 4 hours, approximately 1 mg. per minute of fatty acids was delivered to and removed from the total plasma, which contained only about 5 mg. of preformed triglycerides. The maximum specific activities of plasma triglyceride fatty acids were only 4 and 15 per cent of the specific activities of the fed stearic acid and tristearin, respectively. The authors suggested that the absorbed triglycerides were not mixing appreciably with the existing plasma triglycerides. Their data did not exclude the possibility that the plasma triglycerides were exchanging rapidly with a large triglyceride pool.

Familial hypoglycemia precipitated by amino acids

Abstract: Mann and Magath (1) in 1922 first described the clinical symptoms associated with hypoglycemia, and in 1924 Harris (2) reviewed its relationship to hyperinsulinism. Since then, numerous articles have appeared in the literature reviewing the causes of hypoglycemia, (3-6) describing individual cases and suggesting various surgical and medical methods of management. Although spontaneous hypoglycemia is evidence of abnormal carbohydrate metabolism, this abnormality may be due to a variety of diseases. The present communication describes three cases of hypoglycemia occurring in one family, and one unrelated case, in which convulsions and profound lowering of the blood glucose were induced by the administration of proteins or amino acids. Webelieve this abnormal relationship between amino acids and glucose metabolism has not been previously described, and will be of great interest, not only to the clinician, but also to the biochemist and physiologist investigating carbohydrate and protein metabolism.

Studies on the circulatory changes in the dog produced by endotoxin from gram-negative microorganisms

Abstract: A clinical problem of increasing magnitude is the occurrence of hypotension in patients with bacteremia associated with the liberation of endotoxin from gram-negative microorganisms (1-3). Although the local vascular effects of endotoxin have been extensively studied in animals, particularly with reference to necrotizing effects on tumors (4, 5) and the Schwartzman reaction (6, 7), the hemodynamic alterations produced by these bacterial products remain unexplained. Endotoxins constitute a group of similar chemical substances identified as protein-polysaccharide complexes (8). In the course of a series of investigations reported elsewhere (9, 10), it was found that the pattern of the shock and the pathological changes in the gastrointestinal tract produced by the intravenous injection of endotoxins derived frotn Brucella melitensis, Escherichia coli, Serratia marcescens 1 and Salmonella typhosa 1

Excretion of hydroxyproline in patients with rheumatic and non-rheumatic diseases.

Abstract: The amino acid hydroxyproline constitutes approximately 13 per cent of collagen (1, 2), and 1 to 2 per cent of elastin (2). It is present in no other protein of the body. For this reason, the determination of hydroxyproline has been utilized for the estimation of collagen in various animal tissues (3), and in the fibrinoid material of the subcutaneous nodule of rheumatoid arthritis (4). It is, at the present time, not clear whether in the diseases of the connective tissue, or \"collagen diseases,\" significant alteration and degradation of the protein collagen occurs. The light microscope studies of Klinge (5) and of Bahrmann (6), who observed swelling of collagen in tissue sections of lesions from patients with rheumatic and other diseases, suggested that these changes do occur. Others (7-9) have shown in addition that swelling and focal degeneration of collagen fibers is a common and striking effect of anaphylactoid hypersensitivity reactions. Using the electron microscope, however, Gross (10) and Gale (11) did not find abnormal fibers in material from lesions of rheumatoid arthritis, rheumatic fever, disseminated lupus erythematosus, and scleroderma. Though Wolpers (12) did observe fibrils lacking cross striations in necrotic areas of old rheumatoid nodules, the fibers were normal in non-necrotic areas and in samples of collagen obtained from Arthus lesions. When cross sections of rheumatoid nodules were submitted to careful X-ray diffraction study by Kellgren, Ball, Astbury, Reed, and Beighton (13) normal collagen patterns were seen where collagen was present in the section, and the pattern of an amorphous material where fibrinoid was present.

THE α2 LIPOPROTEINS OF HUMAN SERUM. CORRELATION OF ULTRACENTRIFUGAL AND ELECTROPHORETIC PROPERTIES

Abstract: Two main groups of lipoproteins have been characterized in the serum of normal adults. These have been termed the a1 and the 8,/ lipoproteins on the basis of their electrophoretic mobility (1-5). The broad spectrum of low density lipoproteins that have been observed particularly in patients with arteriosclerosis by means of the analytical ultracentrifuge (6) have not been classified in terms of electrophoretic mobility because of the difficulties in characterization by classical electrophoretic procedures (7-9). Nevertheless, these lipoproteins have usually been considered as /3 lipoproteins. Electrophoresis on filter paper, obviating solution density problems and permitting lipid analyses of the more stable whole serum has revealed the two main \"alpha\" and \"beta\" lipoprotein components. Another fraction observed at the site of origin is considered to represent adsorbed lipoproteins (4, 5) particularly the chylomicrons (10). This fraction is not observed by zone electrophoresis in a starch supporting medium, but an additional lipoprotein peak in the a2 region has been found in the sera of fasting normal (4, 11) and arteriosclerotic (12) individuals. Relatively little information is available regarding this component except that it was shown to rise after meals, particularly fatty meals, as indicated by phospholipid determinations (11). The present report represents an attempt to define the a2 lipoproteins further in terms of both zone electrophoretic and density ultracentrifugal properties. This fraction was examined in the sera of a limited group of fasting normal and arteriosclerotic individuals and was found to consist primarily of lipoproteins less dense than d2\" 1.018.

The miscible pool and turnover rate of hydrocortisone in man

Abstract: In 1948, Mason and Sprague (1) reported the isolation of hydrocortisone from the urine of a patient with Cushing's syndrome, and thus provided evidence that hydrocortisone was produced by the human adrenal cortex. Subsequently, hydrocortisone was found to be one of the principal corticoids in human adrenal gland perfusates (2) and in human peripheral blood (3). These observations strongly suggest that hydrocortisone may be the principal corticosteroid secreted by the adrenal cortex of man. Recent studies (4, 5) utilizing hydrocortisone-4-Cli have elucidated much new information regarding the metabolism and physiological disposition in man of this naturally occurring adrenal steroid. The availability of labeled hydrocortisone has made possible the direct estimation of the magnitude of the reservoir of hydrocortisone in the body, and the rate at which new, non-isotopic hydrocortisone is synthesized in the body and enters the reservoir. This report is concerned with the experimental determination of the magnitude of the miscible pool of hydrocortisone and the rate of its turnover in man. These estimations depend upon serial measurements of the specific activity of circulating hydrocortisone after the infusion of trace quantities of hydrocortisone4-0C1 and analyses of these data utilizing conventional turnover calculations (6, 7). Observations have been made in normal subjects, and subjects receiving adrenocorticotropin and A1 cortisone (prednisone).

Thyroxine-binding by sera of pregnant women, new-born infants, and women with spontaneous abortion

Abstract: Among the many physiological alterations which may occur during pregnancy are thyromegaly (1), augmented thyroidal avidity for iodine (2, 3), and increase in the concentration of circulating thyroid hormone (4, 5). This triad of anatomical and functional alterations is ordinarily considered to be diagnostic of thyrotoxicosis. Paradoxically, however, these findings are neither accompanied by symptomatic stigmata of hyperthyroidism, nor are they associated, during the first half of pregnancy, with increase in the basal metabolic rate. Although the basal metabolic rate increases during the latter half of pregnancy, this change has been ascribed by some to fetal needs, and not to alterations in maternal energy requirements (6). The origins and consequences of this unique functional dissociation are unknown. Recently there has been considerable interest in the physiological role and physicochemical properties of the specific thyroxine-binding protein or proteins of plasma (TBP). Although the physiological role of TBP has not been elucidated, demonstration of this alpha globulin moiety in 1952 provided another parameter of thyroidal economy which is susceptible to measurement (7-11). Even earlier it had been suggested that the increased SPI of pregnancy might result from an alteration in the manner in which thyroxine in plasma is protein-bound (12, 13). Therefore, it appeared possible that study of the thyroxine-

The pressor effect of the antidiuretic principle of the posterior pituitary in orthostatic hypotension

Abstract: Although the antidiuretic property of posterior pituitary extracts is well established, investigators have repeatedly failed to demonstrate a pressor effect of these substances in man (1, 2). Consequently, the hemodynamic effects of posterior pituitary hormones have received relatively little attention. However, it is known that posterior pituitary extracts do produce an increase in arterial pressure after injection into anesthetized or spinal animals (3, 4). The purpose of this report is to present observations on a disease state in man in which it was found that posterior pituitary hormones have a marked effect on arterial pressure.