Charles Ragan

Differential agglutination of normal and sensitized sheep erythrocytes by sera of patients with rheumatoid arthritis.

Summary A differential sheep cell agglutination test is described wherein the agglutination titers of human serum for normal and sensitized sheep erythrocytes are compared. High differential titers have been found to occur almost solely with the sera of patients suffering from active rheumatoid arthritis. Some of the features of this serological phenomenon are pointed out, together with its possible practical applications.

Natural history of lupus erythematosus disseminatus.

Excerpt INTRODUCTION The new vistas opened by the advent of cortisone and corticotrophin in the treatment of lupus erythematosus disseminatus (LED) emphasize the importance of an understanding of i...

Effect of adrenocorticotrophic hormone (ACTH) on rheumatoid arthritis

T HIS report deals with observations on eight patients with rheumatoid arthritis who have been treated with adrenocorticotrophic hormone (ACTH). The dramatic symptomatic response of patients with rheumatoid arthritis to the administration of ACTH described by Hench et al.’ has been amply confirmed. An understanding of the mechanism of this response or, in fact, of the mechanism of the activity of rheumatoid arthritis has not yet been found. Before the advent of cortisone and ACTH for clinical usage any decrease in activity of rheumatoid arthritis, when it occurred, took place gradually. With ACTH, and as reported by Hench with cortisone,’ a rapid and complete defervescence of activity takes place and activity usually returns when the medication is discontinued. This type of response suggests that the primary cause of the disease may not be affected by the administration of cortisone or ACTH, the effects being only on those factors which constitute the reaction of the host to the mechanisms that initiate and sustain the disease. These secondary factors constitute what is vaguely termed “activity” of the disease. Some of them are purely subjective, such as pain, easy fatiguability, lassitude and general malaise. Others are objective and capable of measurement, such as the inflammation of the joints, rapid erythrocyte sedimentation rate, fever and anemia. Most of our studies to determine the mode of action of ACTH in rheumatoid arthritis gave negative results. The data are recorded to save repetition on the part of subsequent workers on this problem. A few possible leads as to the mechanism of action are presented but these require more extensive study and confirmation.

THE HYALURONIC ACID OF SYNOVIAL FLUID IN RHEUMATOID ARTHRITIS

Rheumatoid arthritis *is considered a disease which involves the connective tissue and supporting structures of the body with its primary nidus in the interfibrillar ground substance of these structures (1). The ground substances are thought to be composed of mucopolysaccharide-protein complexes. The nature of two of the polysaccharides is known-chondroitin sulfuric acid and hyaluronic acid. The latter has been isolated from skin, the vitreous of the eye and from synovial fluid (2). The synovial space has been regarded as an enlarged tissue space (3) and synovial fluid may be obtained with relative ease in many patients with rheumatoid arthritis. A study of the hyaluronic acid in the synovial fluid of patients with rheumatoid arthritis in contrast to normals seemed worthwhile as the characteristics of the hyaluronic acid thus obtained might parallel changes in other mucopolysaccharides in the smaller connective tissue spaces throughout the body. Hyaluronic acid in synovial fluid is the component of the fluid which is responsible for its high viscosity (4). A variety of quantitative viscosimetric methods have been applied to the viscous nature of synovial fluid since 1925 (5). These have yielded conflicting data but most seem to agree that normal joint fluid is a very viscous material (6). Bauer, Ropes and Waine (3) demonstrated that there is a wide range of viscosity values obtained from both normal and pathological fluids. We have shown that the viscosity of normal human knee joint fluid varies inversely with the degree of peripheral edema present (7). When joint fluid or purified hyaluronic acid is diluted with 0.85 per cent saline or distilled water an exponential curve is obtained (8, 9), and with fluids of high viscosity small increments of diluent fluid cause marked decreases in viscosity. For these reasons, viscosity alone cannot be taken as an index of the concentration of hyaluronic acid or of the extent of polymerization of the mucopolysaccharide. The concentration of hyaluronic acid may be approximated by the mucinclot method of Bauer et al. (3), but the clot thus formed contains both protein and hyaluronic acid and changes in protein concentration could cause errors in the determination of hyaluronic acid concentration. Recently a method has been described whereby the hyaluronic acid content of 1 cc. of fluid can be determined with an accuracy sufficient for a biological method (2).

MUSCLE INVOLVEMENT IN BOECK'S SARCOID

Excerpt Sarcoidosis is a disorder which may affect any part of the body. Most frequently the lymph nodes, liver, spleen, lungs, skin, eyes and the small bones of the hands and feet are involved,1bu...

Diagnostic significance of the muscle biopsy

Abstract 1.1. A retrospective evaluation of the value of the random skeletal muscle biopsy at the Columbia-Presbyterian Medical Center in the eleven year period from 1946 through 1956 is reported. 2.2. The changes seen on examination of muscle tissue were of value in diagnosis in some patients with sarcoidosis, polyarteritis and trichinosis. 3.3. The characteristic lesion in the muscle in sarcoidosis was the epithelioid cell granuloma with giant cells, such as is found in other tissues in this disorder. This lesion was found in muscle in slightly more than 50 per cent of patients with sarcoidosis. 4.4. In 37 per cent of patients with polyarteritis, acute arteritis with necrosis of the vessel wall, inflammatory cell infiltration, with or without granulomas, was found in the muscle. 5.5. In only three of fifteen patients with trichinosis were trichinae seen in the muscle specimen obtained at biopsy. 6.6. In the aforementioned and in other medical disorders, muscle fiber degeneration associated with inflammatory changes was often encountered. Although such lesions occurred with greater frequency and perhaps with greater severity in the muscles of patients with dermatomyositis and polymyositis, they were found in such a wide variety of disorders that they could not be considered to have diagnostic specificity.

Viscosity of Normal Human Synovial Fluid

Conclusions 1. The viscosity of normal human knee joint fluid is greater than thatof fluid found in most pathological conditions. 2. The decreased viscosity of joint fluids found in pathologiczl ytates may be clue to one of two factors or to both. (a) dilution with extracellular water. (b) depolymerization or dissociation of a highly polymerized hyaluronic acid by hyaluronidase.

Hyaluronic acid-hyaluronidase and the rheumatic diseases.

‘The pathogeiicsis of the rheumatic diseases is obscure. Apparently, the disease process is localized in the connective tissue and particularly in the interfibrillar material, which is composed in part of one or both of the mucopolysaccharides-chondroitin sulfuric acid and hyaluronic acid. The only microorganisms known to produce hyaluronic acid are groups A and C hemolytic streptococci in the mucoid phase. Nonmucoid hemolytic streptococci may produce hyaluronidase, as do many other microorganisms, such as pneumococci, staphylococci, and some gas-producing anaerobes. I t appears significant that, following an outbreak of sore throat caused by type 4 streptococci (a hyaluronidase-producing strain) in a convalescent home for rheumatic children, Kuttner observed no recrudescence of rheumatic activity, while in previous years, sore throat due to other types of hemolytic streptococci led to a definite number of recurrences. In the light of Sallman and Birkeland’s work, this interpretation may have to be revised. Hyaluronic acid has been isolated from normal synovial fluids of animals and abnormal synovial fluids from man. Synovial fluid from the knees of normal human beings cannot be obtained in sufficient quantity for chemical isolation. The normal fluids, on dilution, acidification, and addition of normal horse serum, form a fibrous clot, whereas under the same conditions most pathologic fluids go into a state of colloidal turbidity. On addition of 0.01 unit of hyaluronidase, an amount insufficient to affect the viscosity or concentration of hyaluronic acid of the material under the experimental conditions, the fiber formation is prevented and the colloidal turbidity seen in pathologic fluids occurs. On dilution of a fluid containing hyaluronate, a straight line is evolved if the log of viscosity is plotted against dilution. In synovial fluid, the viscosity alone cannot be used as an index of polymerization of the hyaluronate, since dilution with extracellular water influences viscosity so markedly. If concentration of hyaluronate, determined turbidimetrically, and viscosity are known, however, using the straight-line relationship existing between log viscosity and concentration, a quotient can be derived which will give an approximation of the mean polymerization of the hyaluronate present in the fluid. A quantitative difference between normal and pathologic fluids was found. In fluids from normal joints, this quotient was always more than 10, while in fluids from patients who had rheumatoid arthritis or rheumatic fever the factor was as low as 1. The activity of the disease was roughly inversely propotional to this factor; the more active the disease, the lower the factor, and, as the activity diminished, the factor rose.

Clinical and metabolic study of 17-hydroxycorticosterone (Kendall Compound F); comparison with cortisone.

Summary The clinical and metabolic effects of parenterally-administered Cpd. F were investigated and compared with those of cortisone. Preliminary observations suggest similar responses but with Cpd. F appearing to be somewhat less active.

Effect of Desoxycorticosterone Acetate upon Plasma Volume in Patients During Ether Anesthesia and Surgical Operation

Summary and Conclusions (1) Plasma volume was determined in patients undergoing ether anesthesia and surgical operation. Seven patients served as controls, 9 received desoxycorticosterone acetate (subcutaneously) at varying time intervals before operation, and 3 received crude adrenal cortical hormone (intravenously) immediately before the anesthetic. (2) Of the 7 patients serving as controls, 2 showed a significant fall in plasma volume during ether anesthesia alone, 5 during the period of operation, and one, one-half hour postoperatively. In none of these controls was there a significant increase in plasma volume during any of the 3 periods studied. (3) Six patients were given desoxycorticosterone acetate subcutan-eously 3 to 4 hours before anesthesia. In this group, 3 patients showed a significant increase in plasma volume during the period of anesthesia alone, one patient during the operation, and 5 patients one-half hour after the operation. There were no patients in this group who showed a significant fall in plasma volume during any of the 3 periods. (4) In this small series of patients who have undergone surgical procedures accompanied by slight blood loss, the decrease in plasma volume associated with ether anesthesia and these surgical procedures is small. This small decrease in plasma volume is not present when patients have been given desoxycorticosterone acetate subcutaneously 3 to 4 hours before operation.