Gene H. Stollerman

Relationship of immune response to group A streptococci to the course of acute, chronic and recurrent rheumatic fever

Abstract The clinical course of rheumatic fever in relation to the factor of streptococcal infection was studied in 580 patients. A high initial titer of either antistreptolysin O, antistreptokinase or antihyaluronidase was found in the sera of 95 per cent of patients who could be studied within the first two months of onset of the rheumatic attack. This figure approached 100 per cent in those studies made closer to the onset of the attack. The rate of fall of these three antibodies bore no relationship to the subsequent clinical course of the rheumatic attack. Following suppressive therapy with aspirin or cortisone, all frank relapses of the disease which were unassociated with new streptococcal infection occurred within two months. Thereafter, the reappearance of frank rheumatic fever was invariably associated with immunologic evidence of new streptococcal infection. The implications of these findings for the management of the rheumatic subject and the effect of antistreptococcal prophylaxis upon the natural history of the disease are discussed.

The relationship of Sydenham's chorea to infection with group A streptococci

Abstract The relationship between chorea minor and streptococcal infections was investigated by means of determination of streptococcal antibodies in patients with chorea. Fifty-one patients with chorea as the only clinical manifestation (pure chorea) were studied. The incidence of elevated streptococcal antibody titers, indicative of recent streptococcal infections, was higher in a group of thirty patients studied within one month from the onset of chorea (73.3 per cent) than in patients studied later (45.4 per cent). This incidence was, however, lower than in a comparable group of patients with other manifestations of rheumatic fever (95 per cent). An analysis of the histories of fifty-five patients with chorea and other manifestations of rheumatic fever showed that the onset of chorea usually follows the onset of the other rheumatic manifestations. A longer lag period between streptococcal infections and chorea minor than between streptococcal infections and the other most common manifestations of rheumatic fever was suggested by these studies. Serial determinations of three streptococcal antibodies were made in ten patients in whom chorea started more than two months after the onset of another rheumatic manifestation. The possibility of intercurrent streptococcal infection was thereby ruled out. By the time chorea appeared, the streptococcal antibody titers were often low, although they were high initially. The interpretation is advanced that the relatively long lag period between streptococcal infections and chorea may explain the lack of immunologic evidence of recent streptococcal infections in some cases of pure chorea. Some clinical and epidemiologic data are discussed in connection with this interpretation. Immunologic studies of the cerebrospinal fluid in fifteen patients with chorea failed to yield information on the pathogenesis of the disease.

The Influence of Rheumatic Fever on Serum Concentrations of the Enzyme, Glutamic Oxalacetic Transaminase

Variations in serum concentration of the enzyme, glutamic oxalacetic transaminase, in 64 patients with rheumatic fever were studied. Elevations were noted in 17 of 26 patients with carditis of definite or questionable activity and transiently in one rheumatic subject with viral myocarditis. Except for one patient with polyarthritis and equivocal evidence of acute cardiac involvement, serum concentrations were normal during noncardiac rheumatic manifestations and inactive carditis. There was no relationship to temperature, sedimentation rate, white blood count or C-reactive protein. Intermittent necrosis of myocardial fibers probably leads to these increased serum transaminase concentrations.

Determination of C-reactive Protein in Serum As a Guide to the Treatment and Management of Rheumatic Fever*

which may be identified by its capacity to form a precipitate with the somatic C-polysaccharide of the pneumococcus.’ It has therefore been named “C-reactive protein” (CRP) .* Minute amounts of this protein may be demonstrated in human serum by a precipitin test employing a specific antiserum obtained from rabbits hyperimmunized by repeated injections of purified C-reactive protein, 3,4 In previous studies it has been demonstrated that the appearance of C-reactive protein in the blood is a non-specific but extremely sensitive indicator of the presence of an inflammatory reaction.* In 1950 Anderson and McCarty5 demonstrated the usefulness of this test for the detection of low-grade inflammation in patients with rheumatic fever. More recently Ziegra and Kuttner’j and Bunim and his associates? have observed the behavior of CRP in the serum of patients treated with antirheumatic agents. The present study adds observations on sixtytwo patients in whom serum C-reactive protein determinations were carried out during various stages of rheumatic fever. The usefulness of this test for the detection of rheumatic activity is demonstrated, and certain limitations emphasized. The patients included in this study were admitted to Irvington House in the acute, chronic or convalescent stages of rheumatic fever. They

Effect of Adrenocortical Hormones on Presence of C-reactive Protein in Blood.

Summary and conclusions The C-reactive protein response in human blood following intravenous injections of typhoid vaccine is described. No significant alteration in the promptness, intensity or duration of this response was noted during the administration of cortisone, ACTH or salicylates. 2. In rabbits the response of the analogous Cx-reactive protein to experimental pneumococcal inf ection is similarly not modified by the adrenal cortical hormones. 3. The experimental results support the clinical impression that the disappearance of C-reactive protein from human blood during antirheumatic therapy with adrenalcortical hormones or with salicylates is secondary to suppression of the inflammatory process rather than a primary effect of these agents upon the metabolism of the C-reactive protein.

Ballistocardiographic study of body acceleration during the acute and convalescent stages of rheumatic fever.

Abstract Ballistocardiograms of body acceleration, velocity, and displacement were recorded serially in 170 children, ranging in age from 6 to 15 years, during various stages of acute rheumatic fever and during convalescence. Similar records were obtained from a control group of 150 children. Changes in the acceleration ballistocardiogram designated as grossly “abnormal” were encountered in 1.3 per cent of the total control group. There was a direct relationship between the severity of acute rheumatic carditis and the incidence and degree of ballistocardiographic abnormality. The incidence of grossly abnormal ballistocardiograms decreased as the acute rheumatic attack subsided. During treatment with either cortisone or salicylates, the ballistocardiogram appeared to reflect the cardiac status of the patient rather than the symptomatic response to the anti-inflammatory effects of therapy. During the first few months of convalescence, patients with the highest incidence of abnormal ballistocardiograms were those who had had clinically evident carditis during the acute stage of the disease. Within six months, the incidence of gross abnormalities in the BCGs in this group decreased significantly. Patients without apparent carditis during the acute stage of the disease had fewer abnormal BCGs during the first three months of convalescence. All reverted to normal after six months. Progressive improvement in the ballistocardiogram occurred despite the persistence of valvular deformity except in some patients with marked cardiac enlargement. This study indicates that marked acceleration BCG changes occur frequently during the acute stages of rheumatic fever, when rheumatic carditis is clinically evident. When clinical manifestations of carditis are absent such changes appear less frequently and are less marked. During convalescence virtually all abnormalities disappear by the end of six months except in those patients whose cardiac reserve is limited by persistent chronic rheumatic carditis or advanced rheumatic heart disease. The acceleration BCG has many advantages over previously described methods for the measurement of body motion. The absence of quantitative criteria to determine the range of normal variation compels dependence upon subjective impressions which at present impose a serious limitation upon the immediate clinical application of the method. The results of this study, however, justify further investigation of the use of the acceleration BCG to detect myocardial involvement in patients with rheumatic fever.