Angelo Taranta

Natural history of rheumatic aortic regurgitation. Criteria predictive of death, congestive heart failure, and angina in young patients.

The medical courses of 174 young patients with aortic regurgitation were followed prospectively for a median of 10 years. The data were analyzed by life-table methods; congestive failure and angina, as well as death, were considered as end points, since the occurrence of the former is considered sufficient indication for aortic valve replacement. Thirty-one patients developed the triad of moderate or marked left ventricular enlargement, two or three electrocardiographic abnormalities, and abnormal blood pressure. Thirty-three percent of these patients either died or had failure or angina within 1 year, 48% within 2 years, 65% within 3 years, and 87% within 6 years from the acquisition of the triad. The 71 patients with none of the above features had uneventful courses. Of the 71 patients with one or two features only seven either died (three) or became symptomatic. These data are useful for patient selection for surgery before symptoms appear.

Complement fixation by antibody fragments.

Rabbit antibodies (7S) degraded by papain into univalent 3.5S fragments fail to fix complement when they combine, but do not precipitate, with the homologous antigens. Divalent 5S fragments obtained by pepsin digestion (composed of fragment I linked to II, but lacking fragment III) also fail to fix complement although they precipitate with homologous antigens. The amount of specific precipitate formed by the 5S antibody fragment is not increased by exposure to complement

POST-STEROID PANNICULITIS

Excerpt The great majority of untoward effects of steroid therapy follow one of two general patterns. Some of them, such as sodium retention, osteoporosis, and decreased resistance to infections, a...

Prevention of Rheumatic Fever

Rheumatic fever is a recurrent disease which frequently can be prevented. Infection with group A streptococci precipitates both initial and recurrent attacks; therefore, prevention of rheumatic fever and rheumatic heart disease depends upon the control of streptococcal infections. This may be accomplished by (1) prevention of streptococcal injections in rheumatic subjects, and (2) early and adequate treatment of streptococcal infections in all individuals.Bacterial endocarditis may result from dental and other surgical procedures in patients with rheumatic or congenital heart disease. When such procedures are undertaken, these patients should be protected by administration of antibiotics in therapeutic doses.

Passive cutaneous anaphylaxis with antibody fragments.

Pepsin-digested rabbit antibody (5S) provoked reverse passive cutaneous anaphylaxis in the guinea pig, but was somewhat less effective, mole for mole, than the native antibody. Fixation of guinea pig complement by the pepsin-digested antibody could not be demonstrated either in vitro or in vivo. Splitting of the 5S fragment into two monovalent fragments (3.5S) markedly reduced the capacity to provoke reverse passive cutaneous anaphylaxis.

Lymphocyte transformation and macrophage migration inhibition by electrofocused and gel-filtered fractions of group A streptococcal filtrate☆

Abstract Culture filtrates of group A streptococci were fractionated either by isoelectric focusing on a sucrose gradient at pH 3–10, or by gel filtration on a G-75 Superfine Sephadex column. Some fractions induced lymphocyte transformation, others inhibition of macrophage migration, and others both. With the two types of fractionation here used the lymphocyte transformation activity was concentrated in a single peak, while the activity responsible for macrophage migration inhibition was scattered over multiple fractions. The significance of these findings is discussed.

Diagnosis of streptococcal pharyngitis and rheumatic fever.

Eradication of streptococci from the throat has been shown to prevent rheumatic fever, so that an accurate diagnosis of streptococcal pharyngitis is desirable. Throat cultures could be better utilized than they have been for this purpose.

AUSCULTATION OF THE HEART BY PHYSICIANS AND BY COMPUTER

THE physician who attempts to canvass the literature on the auscultatory phenomena of the heart is likely to be disturbed by its inconsistencies. Were these auscultatory phenomena of marginal clinical importance, the inconsistencies would have only academic interest. They are not: on them hinge diagnoses which are of great practical importance, because they carry widely different prognoses, treatments and prophylactic plans. Thus a patient with congenital heart disease—even if asymptomatic—may benefit from a correct diagnosis because relatively simple precautions may prevent a serious complication to which he is prone: subacute bacterial endocarditis. Patients with asymptomatic rheumatic heart disease may be protected not only from bacterial endocarditis but also from rheumatic recurrences, which are likely to affect their heart seriously. In other patients fever of unknown origin or hematuria detection of a heart murmur may prompt the diagnosis of subacute bacterial endocarditis, a diagnosis which, made in time, may save their lives. In patients with acute rheumatic fever the kind of murmurs detected may make the difference between the expectancy of a normal life and that of a shortened, severely limited one. It is not widely appreciated that physicians differ considerably in their perception and interpretation of heart murmurs, although such discrepancies have been occasionally reported. Since these discrepancies may explain in part some of the controversies about the natural history of rheumatic heart disease, and because they demean the value of clinical auscultation of the heart, our group has undertaken a detailed study of them. At the same time, it appeared that automatic data-processing could be applied with advantage to the study of the auscultatory phenomena of the heart, a process which we have hopefully, if perhaps inaccurately, called auscultation by computer.

Release of macrophage migration inhibitory factor(s) from lymphocytes stimulated by streptococcal preparations.

Abstract Lymphocytes from apparently healthy subjects, incubated for 5 hours with cellular components or extracellular products of group A streptococci and then washed and reincubated, were found to release factor(s) capable of inhibiting guinea pig lung macrophage migration (“ indirect method ”). Inhibitition of macrophage migration was also obtained when the same preparations were tested directly on guinea pig lung cells, a macrophage-lymphocyte population (“ direct method ”). The guinea pigs had not been experimentally sensitized. The inhibition of migration appeared to depend on the presence of lymphocytes among the macrophages, since macrophages purified by repeatedly discarding nonadherent cells proved resistant to the migration inhibiting activity of the most active Streptococcal preparation, a 20 × concentrated filtrate. Reconstitution of the original lymphocyte-macrophage mixture reestablished the reactivity. The macrophage migration inhibition did not correlate with the age of the guinea pigs. It could not be obtained with preparations of group D streptococci or of Salmonella paratyphi . Group C streptococci did not inhibit the macrophage migration with the indirect method, but it did with the direct one. The factor(s) released into the medium on stimulation of apparently normal lymphocytes by Streptococcal preparations was relatively heat resistant, nondialyzable, and DNase and RNase resistant; its release was inhibited by puromycin. Pretreatment of the cells with trypsin prevented the absorption of the factor(s) and left migration unaffected. These characteristics are similar to those previously described for the migration inhibitory factor (MIF) produced by the interaction of sensitized lymphocytes and specific antigens. Whether or not these similarities indicate an identity remains to be determined.

LYMPHOCYTE MITOGENS OF STAPHYLOCOCCAL ORIGIN

There are several reasons why the study of lymphocyte mitogens of bacterial origin may be interesting, and even useful. Generally, one might say that anything that reacts with lymphocytes is important simply because the lymphocytes are important, at least to immunologists. More specifically, substances that react with the lymphocyte surface may become useful reagents with which to study the surface of the lymphocytes, and thus may help to elucidate this intriguing structure. Since some other substances that stimulate lymphocytes to transform and divide, notably antilymphocytic serum, are immunosuppressant,l it is permissible to speculate that the bacterial mitogens may also have immunosuppressive properties. Last but not least is the possibility that bacterial products which stimulate lymphocytes may, by so doing, injure the host. I will first review some of the information that supports this latter concept. From studies in vitro, it has become apparent that the small circulating lymphocyte is not the end-stage cell it was so long supposed to be, but can be activated to transform into a large cell with a looser nucleus, richer in cytoplasm, and endowed with nucleoli and vacuoles (FIGURE 1 ) . This cell is indistinguishable from a naturally occurring lymphoblast and is capable of mitosis. This transformation was first obtained with phytohemagglutinin, a lectin from fava beans.? Because the lymphocytes of all normal human subjects responded in this manner, because a very high percentage of the lymphocytes of each subject transformed, and because the lymphocytes of newborn infants, which are presumably immunologically virgin, also transformed, the response of lymphocytes to phytohemagglutinin (PHA) is generally considered nonspecific (by which is meant nonimmunologic) in nature, and PHA is considered. to be a nonspecific lymphocyte activator. Shortly thereafter it was found that antigens, typically tuberculin, to which a given subject had previously been sensitized, could also induce transformation when added to the subject’s lymphocytes in c u l t ~ r e . ~ Some bacterial preparations of streptococcal 4, and staphylococcal origin were found to have properties similar to PHA, and like PHA have been considered nonspecific mitogens, although the evidence is not quite conclusive. Almost concomitantly with these early studies on the agents of lymphocyte activation, observations started on the biologic activity of activated lymphocytes or lyrnphoblasts. Holm and Perlman reported that lymphocytes, activated specifically or nonspecifically,* killed other cells. This cytotoxic effect appeared to depend on direct cell-to-cell contact. A number of other effects,