Pathogenesis Of Rheumatic Fever Research Articles

Circulating immune complexes in rheumatic fever.

We measured the circulating immune complex levels in patients with rheumatic fever using the following three methods: the C1q binding test, the conglutinin binding test and Raji cell radioimmunoassay. Thirty-four samples from 21 patients with rheumatic fever were examined, and circulating immune complexes were detected in 47.6% of the patients by one or more of these methods. Especially by the C1q binding test, the sera obtained in the acute phase were found to contain the circulating immune complexes with higher frequency than those obtained in the post-acute phase. Therefore, the C1q binding test was more likely to be useful in the acute phase of this disease. The present study suggests that the circulating immune complexes are related to the pathogenesis of rheumatic fever.

Occurrence of Infection with Group B Coxsackievirus in Rheumatic and Nonrheumatic Filipino Children

The pathogenesis of rheumatic fever has been linked to various immune mechanisms involving streptococcal antibodies and heart tissue antigens. Latent myocarditis due to group B coxsackievirus has also been considered as a possible conditioning factor. The validity of the role of infection with group B coxsackievirus in rheumatic fever was tested by determining the incidence of type-specific neutralizing antibodies in sera of Filipino children. Analysis of the results by means of a normal Z-test showed that the incidence in rheumatic children was not statistically significant in comparison to the incidence in asymptomatic children.

Adherence of Group A Streptococci to Pharyngeal Cells: A Role In The Pathogenesis of Rheumatic Fever

We used an assay in vitro to investigate the possible role of streptococcal adherence to human pharyngeal cells in the pathogenesis of acute rheumatic fever. There was no difference in adherence of rheumatic fever-associated and non-associated strains of group A streptococci to pooled pharyngeal cells of normal people. Likewise, streptococci not associated with rheumatic fever adhered equally well to cells taken from normal people and from patients with rheumatic heart disease. However, the pharyngeal cells of all nine rheumatic heart disease patients tested had increased avidity for adherence for a rheumatic fever-associated strain of streptococcus compared to the pharyngeal cells obtained from age- and sex-matched controls. Increased streptococcal adherence to pharyngeal cells of rheumatic fever-prone patients may play a role in the pathogenesis of rheumatic fever.

Streptococcal Immunology: Protection Versus Injury

Excerpt The pathogenesis of rheumatic fever and rheumatic carditis is still obscure despite a voluminous literature on group A streptococcal immunology (1). The popular notion, however, that rheuma...

Suppression of the antistreptolysin O response by cholesterol and by lipid extracts of rabbit skin.

Lipids extracted from rabbit skin block the hemolytic capacity of SO and also suppress the neutralizing antibody response to this streptococcal extracellular antigen in rabbith immunized intravenosly. The modification in antibody response is specific for SO; the antibody responses to streptococcal DNase B and to streptococcal NADase are not affected. Cholesterol, a lipid present in abundance in skin, has a similar specific effect on the antigenicity of SO and may be the component responsible for the demonstrated effects of these lipid extracts of skin. In vitro experiments indicate that lipid extracts of rabbit skin have a greater capacity to block the hemolytic capacity of SO than do lipid extracts of rabbit heart, kidney, lung, liver, or spleen. These data support the view that the feeble ASO response observed in patients with streptococcal pyoderma is a result of the abundance of a local lipid inhibitor, such as cholesterol, in the skin. They may also bear on the pathogenesis of rheumatic fever, a complication which apparently does not occur following group A streptococcal pyoderma. Two possible explanations for this remarkable epidemiologic observation, both related to the presence of a local inhibitor, are considered: (a) suppression of the ASO response, the magnitude of which has been correlated with the risk of developing rheumatic fever after streptococcal infection of the throat, and (b) inhibition of the toxicity of SO, which has been shown to have a direct toxic effect on the mammalian heart and on isolated beating myocytes.

Prevention of streptococcal sequelae by penicillin prophylaxis: a reassessment.

In conclusion, the diagnosis of streptococcal infection lacks precision, and as long as this is so, reliance must be placed on trained clinical judgement together with bacteriological studies. There is some evidence for an evolutionary drift in the relationship between the streptococcus and man, a drift that is compatible with the natural history of other diseases and with the accomodations observed in nature among other species during the course of evolutionary events. If, as a result of recent accomodations between man and the group A streptococcus, the risk of rheumatic fever is less, an undefinable risk nevertheless remains. There was even a military outbreak of rheumatic fever in England several years ago, and on that island--we are told--rheumatic fever has been banned for years. The current recommendations of the American Heart Association for the secondary prevention of rheumatic fever I judge acceptable for use in the United States. I have, however, raised the possibility that they may be inadequate for the prevention of second attacks in other populations where the environmental, socioeconomic, bacteriological, and nutritional circumstances are different from our own. Studies designed to reexamine these questions may, in the end, refocus our attention on the importance of host factors in the occurrence and pathogenesis of rheumatic fever.

HUMORAL AND CELLULAR IMMUNE RESPONSES TO STREPTOCOCCI, INFLUENZA AND OTHER ANTIGENS IN AUSTRALIAN ABORIGINAL SCHOOL CHILDREN

SYNOPSIS Aboriginal school children with elevated erythrocyte sedimentation rates were selected, and associated features of growth retardation, hyperimmunoglobulinaemia, high streptococcal carrier rates and antibody levels, and high loads of bowel parasite infestation, noted previously, were confirmed. Medical records showed these children to have had significant growth retardation in infancy, which suggested an association with previous protein-calorie malnutrition. Antibody responses of these children to influenza vaccine were significantly poorer than controls, both in the magnitude of antibody rise and the proportion of children showing significant rises in titre. Some improvement in antibody response followed treatment of chronic streptococcal infection, or of bowel parasites. Cell-mediated immune responses, as measured by lymphocyte transformation in vitro in response to specific antigens streptolysin O, tetanus toxoid, non-specific mitogens PHA and streptolysin S, and also by delayed hypersensitivity reactions to monilia antigen on skin testing, were diminished in children with high ESR, relative to controls. However, enhanced cellular responses in the abnormal children occurred to influenza A2 antigen, and to streptococcal group A polysaccharide, the latter possibly explaining chronic low-grade tissue damage noted previously in these children. These findings are discussed in relation to resistance to infection and the pathogenesis of rheumatic fever, and a possible basis suggested in acquired change in function of the thymus, perhaps related to protein-calorie malnutrition in infancy.

Pathogenesis of rheumatic fever.

Pathogenesis of rheumatic fever.

Arthritis and Allied Conditions, ed 7.

When the first edition of Arthritis and Allied Conditions , published by the late Bernard T. Comroe, appeared in 1940 this field of medicine was derelict. Since then, a tremendous growth in knowledge and interest in rheumatic diseases has developed. After Comroe's death, J. L. Hollander assumed the responsibility of editorship and the task of keeping this textbook up to date. To achieve this goal, nine entirely new chapters have been added to the seventh edition; they describe new disease entities such as pseudogout and the arthritis of familial Mediterranean fever. Chapters have been added dealing with the pathology, epidemiology, and pathogenesis of rheumatic fever and the etiology and pathogenesis of gout. In addition, 20 chapters have been reorganized and rewritten, primarily by new authors. Contributors responsible for the 77 chapters include leading authorities in the field of rheumatic disease. Accordingly, most of the sections are filled with relevant information. In

Rheumatic Nodules Wanted

In the course of tissue culture studies on the pathogenesis of rheumatic fever, we are in need of rheumatic nodules which have recently formed in the course of rheumatic carditis. These structures have become rare due to the recent decrease in the prevalence and severity of acute rheumatic fever and the widespread use of steroids. The nodule should be situated on the extremities, be readily accessible to biopsy, and, preferably, be just in the process of forming, although nodules of any age would be welcome.

Rheumatic Fever: Diagnosis, Management and Prevention

Rheumatic fever has been intensively studied clinically over the last half-century. Because of the sequelae of heart valvular scarring and because children are so prominently affected, the disease has commanded exceptional attention from clinical investigators. Since streptococcal infections are important in the pathogenesis of rheumatic fever, microbiologists have joined the effort in recent years. From this intensive clinical and microbiological research has emerged a remarkably complete documentation of the natural history of rheumatic fever, with statistical-clinical correlation of events from the onset of the inciting streptococcal pharyngitis to the progress of the valvular heart disease. Drs. Markowitz and Kuttner have done a remarkable job of synthesizing from many publications a composite picture of rheumatic fever. Their work is not simply scholarly but reflects their years of clinical experience, contemplation and research in rheumatic fever and poststreptococcal disease states. The writing is that of the seasoned and experienced physician, answering the

PRESENCE OF BOUND IMMUNOGLOBULINS AND COMPLEMENT IN THE MYOCARDIUM IN ACUTE RHEUMATIC FEVER. ASSOCIATION WITH CARDIAC FAILURE.

RECENT evidence has supported the concept that the Group A streptococcus possesses antigens immunologically related to human heart tissue1 2 3 and that crossreactive autoimmunity to heart may be stimulated in certain persons after streptococcal infection.4 It has been observed further that such crossreactive autoantibodies are associated with both the poststreptococcal state and rheumatic heart disease.4 Consistent with the possible role of autoimmunity in the pathogenesis of rheumatic fever are the additional observations of focal deposits of bound gamma globulin in the myocardium of 18 per cent of 100 biopsies of the rheumatic atrial appendage studied,5 and of extensive and massive deposition . . .

The pathogenesis of rheumatic fever--a concept.

THE PATHOGENESIS OF RHEUMATIC FEVER—A CONCEPT ALVINF. COBURN, M.D.* Those who refuse to go beyond fact rarely get as far as fact; and anyone who has studied the hbtory ofscience knows that almost every great step therein has been made by the "anticipation ofnature," that, by the invention ofa hypothesb which, though verifiable, often had little foundation to start with; and not infrequently, in spite ofa long career ofusefulness, turned out to be wholly erroneous in the long run. Thomas Henry Huxley I.fustification This is an exposition ofa "hunch." Since it is not a review, observations ofothers will be used for the purpose ofthe argument without reference to an extensive literature. It is not expected that the speculative ideas presented will be convincing; nevertheless, it is hoped that a new approach to an old disease problem may be provocative. The evidence, neither confirmed nor unconfirmed, is mostly circumstantial. No significant relationships are established; this is a recording ofwhat may be concurrent associations . The hypothesis is that lipids protect against activity ofthe rheumatic process. The favorable effect with which this hypothesis deals is that the essential lipid requirements may be attained through diets in infancy and childhood. Moreover, the concept that lipids have a protective role is now ofmore than academic interest; gas chromatography has developed to a degree that the hypothesis can be tested. False or true, the very testing ofthe idea will open new vistas in lipid physiology. Furthermore, as stated byWilliam Trotter: "In science the primary duty ofideas is to be useful and interesting even more than to be true." * Associate Professor ofPediatrics, New York Medical College, New York City. Thb paper was delivered as a lecture September 27, i960, at St. Bartholomew's Hospital, London. Submitted for publication October, i960. Author's present address: Milford Road, Scarborough, Tobago, West Indies. 493 The solution ofmedical problems, like the rheumatic mechanism, may depend on new machines and new techniques—for example, gas chromatography [i]. But this does not mean that creativity in the biological sciences will necessarily stem from new inventions. In the case ofthe physical sciences, it is stated that "most natural phenomena, at all events ofthe inanimate world, have been pretty fully scrutinized" [2]. Emphasis is placed on "the importance of new methods as an aid to creative ideas." This may be true for the inanimate, but medicine is peculiarly animate. It is need that spawns concepts, and it is creative ideas that seek new tools and new techniques. Furthermore, unlike the physicist or chemist, the medical investigator cannot place his reasoning on a purely abstract plane. Furthermore, he must lean heavily on intuition. It now seems clear that a relatively new method, gas chromatography, may permit an attack on the role oflipids at a point where rheumatic fever research has long been stymied. Nevertheless, the successful application ofthis technique to obtain critical information will depend on intuitive planning. It will require that essential "mark" whichwas described bythe late president ofHarvard, A. Lawrence Lowell: "The mark ofan educated man is the ability to make a reasoned guess on the basis ofinsufficient information." Insufficient information is the hallmark of rheumatic fever research. Lord Adrian [2] points out thatthe prescription for the physical sciences may not be applicable to diseases "like rheumatoid arthritis or disseminated sclerosis." He states: "We have to study a complex situation which is continually altering in directions beyond our control." This is true of most disease problems, and it is this continual shifting ofthe many variables in rheumatic fever that attracts the adventuresome explorer. It is this adventuring on one's own into the unknown that has lured the original mind into this unpromising area of medical research. On the encouraging side ofthe ledger is the fact that most ofmedicine's advances have come from adventuresome minds of this character, from uncommitted investigators with worries, with needs, with inspired guesses, with "hunches," and finally with the birth of germinal ideas that have proved revolutionary. Few of medicine's revolutionary changes have evolved from systematic analyses, or from any rational processes, or even from the customary, logical pknning. The greatest advances have been unpredictable. They have come from men intrigued by some unusual...

Immunologic relationship of group A streptococcal strains and human heart tissue. Possible significance for the pathogenesis of rheumatic fever

Immunologic relationship of group A streptococcal strains and human heart tissue. Possible significance for the pathogenesis of rheumatic fever

Rheumatic fever in Hawaii.

Rheumatic fever is generally considered to be comparatively prevalent in the temperate zone and uncommon in subtropical or tropical climates. 1 The purpose of this seminar is to report on a 5-year experience with acute rheumatic fever at the Kauikeolani Children's Hospital in Honolulu in order to emphasize the relative frequency of this disease in Hawaii. During the years 1955 through 1959, ninety-one cases of acute rheumatic fever were seen during the first attack of the disease at Children's Hospital. Although the incidence had been approximately 0.6% of the total medical admissions for the years 1955 through 1959, there was a fourfold increase in 1959 to 2.3%. The cases from 1955 through 1958 were reviewed mainly from the charts, while those of 1959 were seen personally by me. Since the exact pathogenesis of rheumatic fever is not fully understood and since climatologic factors may play a role in precipitating or

L-norepinephrine and the pathogenesis of rheumatic fever.

L-norepinephrine and the pathogenesis of rheumatic fever.

The analysis of streptococcal infections. V. Cardiotoxicity of streptolysin O for rabbits in vivo.

1. The rapid death which occurred after intravenous injection of activated streptolysin O from. Group A or Group C streptococci was always preceded by profound electrocardiographic alterations. After several multiples of the LD(50) doses, cardiac electrical arrest or fibrillation could occur within 2 to 4 seconds after completion of the injection. 2. The streptolysin O preparations used were rather highly purified, but were known to be contaminated with small amounts of one or two other immunologically distinct components. Evidence that the observed results were due to streptolysin O was obtained by tests of the reversibly oxidized materials, and by cholesterol inactivation, as well as by in vivo protection with human gamma globulin rich in antistreptolysin antibodies. 3. Four non-streptolysin streptococcal antigens, partially or highly purified, failed to produce similar electrocardiographic changes, and were much less toxic. One of these was 3 X recrystallized and 1 X rechromatographed streptococcal proteinase. Shigella paradysenteriae type III endotoxin also did not produce striking electrocardiographic abnormalities. 4. A working hypothesis has been developed implicating streptolysin O as the etiological streptococcal factor responsible for the pathogenesis of rheumatic fever, which seems to account for the principal features of this illness.

The concept of collagen diseases in medicine.

The topic of this address was suggested by the Program Committee and I have accepted it with some apprehension. While my co-workers and I (1) are responsible for the term and a somewhat vague concept behind it, I do not feel that we have contributed very much to its further elucidation. Yet great advances have been made by others in the nearly twenty years since the term was.. proposed as an heuristic idea. which, if further explored, might have som~ .importance for the comprehension of the nature and pathogenesis of certain puzzling maladies. I should like to present to you the evolution of observations and thoughts which have led to theooncept and the sequence of investigations which mark the progress .of our knowledge within the past t\VO decades. The term collagen is generally used synonymously with that of diseases of the connective tissue. I shall later in my presentation touch upon the reason we preferred the former designation, but I might say here that I do not object to the latter term if one is aware of the assumptions upon which both terms are predicated. A systemic implication of the fibrous tissue was postulated in 1838 by Bouillaud (2) to account for the simultaneous involvement of the joints and of the heart in acute rheumatic fever; but this induction, important as it was for diagnosis and prognosis in clinical medicine, did not stimulate investigations or' the pathogenesis of rheumatic fever. One can understand this failure if one considers the state of information about the connective tissue one hundred and twenty years ago. Nearly up until that date it had been regarded as a primordial tissue endowed with almost miraculous potencies of proliferation and unlimited differentiation. But a reaction had taken place in Bouillaud's time, and it had become an insignificant component of the animal

L-Norepinephrine and the Pathogenesis of Rheumatic Fever: Brief Statement in Connection with the Etiology of Rheumatic Inflammation

L-Norepinephrine and the Pathogenesis of Rheumatic Fever: Brief Statement in Connection with the Etiology of Rheumatic Inflammation

Is there a rheumatic constitution?

Summary 1. No characteristic hair color or eye color was found among patients with rheumatic fever. 2. Pallor of the skin occurred in52.4 per cent of patients with acute rheumatic fever but was not a prominent feature in inactive rheumatic subjects. 3. No evidence of racial susceptibilityto rheumatic fever was found in this study. 4. Most patients with rheumatic feverhave a well-proportioned body build with a paucity of both the asthenic and hypersthenic body types. 5. A definite hyperextensibility ofthe metacarpophalangeal joints was demonstrated in both active and inactive rheumatics as compared with controls. 6. Blood group distribution amongrheumatic subjects was not statistically different from that in the general population. 7. In a small group of rheumatic patients, there were 24 per cent who were nonsecretors of ABO substance in the saliva. This is slightly higher than the expected percentage in the general population. The possible relationship to the pathogenesis of rheumatic fever is discussed.