The group specific polysaccharide antibody in children with non-suppurative sequelae of group A streptococcal infection.

The kinetics of the group A specific polysaccharide antibody were studied in children with acute rheumatic fever who had no carditis, children with acute rheumatic fever who had carditis and developed rheumatic heard disease and in children with acute poststreptococcal glomerulonephritis. The children with rheumatic fever who had carditis and those who did not, were kept on continuous antistreptococcal prophylaxis. In the group of children who developed rheumatic heart disease the titer of the antibody at onset was significantly higher than those who had rheumatic fever but no carditis (P = 0.01). After a mean follow-up period of three years, a high titer was maintained in children who developed rheumatic heart disease only and was significantly higher than that found in children with rheumatic fever who had no carditis (P = 0.001) and in children with poststerptococcal nephritis (P = 0.001).

Acute rheumatic fever and the evolution of rheumatic heart disease: a prospective 12 year follow-up report.

Sixty four children who presented with the initial attack of acute rheumatic fever and maintained continuous regular secondary prophylaxis, were followed up prospectively for 12.3 years (an observation period of 775 patient-years). The prevalence rate of rheumatic heart disease in the 29 children who had carditis in the initial attack and in the 35 children who had no carditis initially was 49 vs 0%, respectively. The overall prevalence rate of rheumatic heart disease was 20%. Mitral incompetence developed in 11 patients (17%), aortic incompetence in 2 (3%) and mitral stenosis in 2 (3%). None of the patients developed aortic stenosis. Two recurrences developed with a recurrence rate of 0.003 per patient per year. One patient needed cardiac surgery and there was no mortality. These data strongly suggest that continuous regular secondary prophylaxis can prevent or significantly reduce the development of mitral and aortic valve stenosis, the prevalence rate of rheumatic heart disease and mortality.

Intracellular kinetics of the activator calcium of rat heart after ischemic arrest and cardioplegia: quantitative comparison of right and left ventricles.

The effects of plain ischemia (34 degrees C) and the protective role of hypothermia (20 degrees C) alone or in combination with cardioplegia (St Thomas' Hospital [STH] or glucose-potassium-nifedipine [GPN]) on the intracellular kinetics of the activator calcium of cardiac muscle were quantified and compared from the interval-force behaviour (mechanical restitution) of right and left ventricles of the perfused rat heart. Plain ischemia caused a major depression in the restitution of force of contraction of both ventricles, deranged the mixed linear-exponential functions by significantly increasing the time constants of the fitted mechanical restitution curves (MRC) and altered the control right/left ventricle interval-force relationship. The right ventricle was found to be more susceptible to ischemic damage than the left ventricle, and its inotropic reserve was virtually abolished by 1 h of plain ischemia. Hypothermic preservation during ischemia improved the mechanical restitution, salvaged the inotropic reserve and optimized right/left ventricle interval-force relationship, but the time constants of the fitted MRCs were still prolonged. However, both the cardioplegic formulations were equally effective in normalizing the time constants of the fitted curves. In general, right ventricle functions were better preserved by STH cardioplegia and left ventricle functions were better preserved by GPN cardioplegia. Cardioplegic interventions did not further improve the ventricular inotropic reserve compared with hypothermic preservation. Additional beneficial effects of cardioplegic formulations were directed towards stabilizing the linear-exponential functions and hence restitution of force of contraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Group A streptococcal strains in Kuwait: a nine-year prospective study of prevalence and associations.

During a period of 9 years (December, 1980, through November, 1989), 407 Group A streptococcal strains were isolated from 294 children with acute rheumatic fever and 303 of their family contacts, 234 children with acute post-streptococcal glomerulonephritis and 242 of their family contacts and 219 children with uncomplicated Group A streptococcal pharyngitis. Of the 407 strains 216 (53%) were M and/or serum opacity factor typable, 143 (35%) were only T typable and 48 (12%) were nontypable. Throughout the period of study the M12 and M1 were the most prevalent strains; however, important changes among the prevalent strains were observed. Although the study started in 1980 the serotypes M18, M81, M3, M15 and M58 made their first appearance 7 to 9 years later. These findings show the value of long term studies in detecting the changes in the prevalence of streptococcal strains in the community. M18 was isolated from three children with nephritis but not from children with rheumatic fever; this association has not been reported before. M12 was isolated from 26% of the nephritic children and their families vs. 7% from the rheumatic children and their families (P less than 0.05) vs. 17% from children with uncomplicated streptococcal pharyngitis. M49 was isolated from 7% of the nephritic children and their families vs. none from rheumatic children and their families vs. 1.4% from children with uncomplicated streptococcal pharyngitis. These findings support the concept of nephritogenicity of some streptococcal strains.(ABSTRACT TRUNCATED AT 250 WORDS)

Human heart sarcolemmal sheath antibodies in children with non-suppurative sequelae of group A streptococcal infections: a follow up study.

The kinetics of the human heart sarcolemmal sheath antibody were studied in children with acute rheumatic fever who had no carditis, children with acute rheumatic fever who had carditis and developed rheumatic heart disease, and in children with acute poststreptococcal glomerulonephritis. The children with rheumatic fever and those who developed valvular heart disease were given continuous secondary antistreptococcal prophylaxis. The titre of antibody at onset was significantly higher than that of the controls in children with acute rheumatic fever and carditis and in children with acute poststreptococcal nephritis. The difference in the antibody titre between children with rheumatic fever who had no carditis and controls was not statistically significant. After a mean follow up of three years, however, a high titre was only maintained in children with rheumatic fever who developed valvular heart disease.

Antibody levels and in vitro lymphoproliferative responses to Streptococcus pyogenes erythrogenic toxin A and mitogen of patients with rheumatic fever.

We investigated the in vitro lymphoproliferative responses to a streptococcal mitogen and erythrogenic toxin A of children with acute rheumatic fever (ARF) and patients with chronic rheumatic heart disease (CRHD). Antibody levels to the streptococcal products were also analyzed in the sera of those with ARF or chronic rheumatic heart disease as well as in the sera of children with streptococcal pharyngitis or poststreptococcal glomerulonephritis. Our results demonstrated that the individuals had depressed lymphoproliferative responses during the active stage of rheumatic fever. The depressed responses were not found either to be induced by time-sensitive mitogen-specific suppressor cells or to be related to a dose-response phenomenon. On the other hand, antibody levels to the extracellular mitogens were significantly elevated in the sera of children with ARF compared with the levels in the rest of the groups. The hyperresponsiveness noted among children with ARF was found to be at a quantitative level and was not due to recognition of more epitopes, as determined by Western blotting (immunoblotting). The profile of immune responsiveness in children with ARF to the streptococcal extracellular mitogens is discussed in relation to the pathogenesis of disease.

Acute rheumatic polyarthritis. The duration of secondary prophylaxis.

Antistreptococcal prophylaxis was discontinued in a group of 44 children who had acute rheumatic polyarthritis with no carditis or chorea during the initial attack and who had completed a mean period of 5 years of secondary prophylaxis and freedom from recurrences. Patients were then followed up for a mean period of 5 years (an observation period of 216 patient-years). Recurrence of disease occurred in 3 patients, with a recurrence rate of 1.4 per 100 patient-years. There was no evidence of carditis during these recurrences and all patients remained free of rheumatic heart disease 10 years after the initial attack. These data demonstrate the relative safety with which continuous antistreptococcal prophylaxis can be discontinued in a selected group of children with rheumatic fever.

Agalactosyl IgG, antibodies to heat shock proteins, and acute rheumatic fever.

In rheumatoid arthritis an increased proportion of the N-linked oligosaccharides on serum IgG terminate with N-acetylglucosamine (agalactosyl IgG). It has recently been shown that group A streptococcal cell wall peptidoglycan/polysaccharide complex may be used to raise monoclonal antibodies which bind to this glycoform of IgG. Patients with rheumatoid arthritis also have increased levels of antibody to the 65 kD and 70 kD families of heat shock proteins, particularly to a bacterial (Mycobacterium bovis) homologue of heat shock protein hsp65. Streptococci must contain similar heat shock proteins. Acute rheumatic fever follows infection with group A streptococci, and these organisms might theoretically evoke antibody to heat shock proteins or changes in the levels of agalactosyl IgG, which is antigenically cross reactive with their cell walls. It is shown here that serum samples from patients with acute rheumatic fever do not differ from those from normal children by these criteria.

Differences in the recovery of right and left ventricular function after ischaemic arrest and cardioplegia.

Differential susceptibility of right (RV) and left (LV) ventricles to plain ischaemia and the contribution of cardioplegia in reducing the ischaemic damage was evaluated in a sheep model of cardiopulmonary bypass. Sheep (n = 16) were equally divided for the two protocols of the study. Each sheep served as its own control. RV and LV functions were studied and compared by plotting ventricular function curves (Starling and Sarnoff). The mathematical centre of mass (COM) for each curve was computed by a polynomial regression program. The COM values of the contractility indices [stroke volume (SV), stroke work (SW)] represented ventricular heterometric reserve. RV and LV heterometric reserve was significantly (P less than 0.01) reduced after 1 h plain ischaemia, and quantitatively this change was more for RV than for LV (P less than 0.05). As compared to LV, a significantly greater reduction in RVSW was brought about by a significantly (P less than 0.01) greater reduction in RVSV, because there were no significant differences between the post-ischaemic recovery in the RV and LV afterloads. Cardioplegic protection nearly normalized filling pressure and contractility (SV, SW) of both ventricles, but major differences were observed in the recovery of compliance. Recovery in the RV compliance exceeded the control values, and quantitatively the recovery in RVSW was slightly more than in LVSW. The results of this study indicate that the RV suffers more damage from plain ischaemic arrest and hence benefits more from the cardioplegic protection.

[Heart catheterization: experience with 1000 examinations]. / K problematice srdecní katetrizace, zkusenosti s 1000 vysetrení.

Catheterization of the right and left heart by the percutaneous technique, incl. Rashkind's septostomy, was performed in 1000 patients with body weights from 2 kg and above between 1977 and 1984. The technique of the examination is described. The patients belonged to the following age groups: 1st day to one year--28%, 1-5 years--28.6%, 6-15 years--31.9%, above 15 years--11.5%. The authors recommend to reduce the incidence of complications by continuous monitoring of the blood pressure during catheterization by means of an arterial catheter. As to complications, they recorded three deaths within 24 hours after catheterization: 2 infants and one adult patient, i.e. a mortality rate of 0.3% as compared with 1.5-3% reported in the literature. As to serious dysrhythmias, there was once ventricular tachycardia and one ventricular fibrillation. In two patients during angiocardiography the contrast substance was injected into the myocardium. Cardiac tamponade was described twice. In one infant on the second day after catheterization a thrombus was removed from the femoral artery. A computer proved useful for the calculation of haemodynamic data.

An association between Gc (vitamin D-binding protein) alleles and susceptibility to rheumatic fever.

Rheumatic fever is associated with exaggerated activity of B cells with massive production of antibody to the Group A streptococcus. Gc (vitamin D-binding protein) is constitutively expressed on B-cell membranes in association with membrane immunoglobulin, and could be involved in cell activation. We therefore looked for associations between the three major Gc alleles and susceptibility to rheumatic fever in a homogeneous Arab population. Patients with tuberculosis or rheumatoid arthritis and control donors, were studied in parallel. Allele frequencies in the controls, rheumatoid and tuberculosis patients were identical to those found in a previous study of normal Arab donors. However, there was a striking association between Gc2 and rheumatic fever. This allele was twice as common in these patients as in controls (p = 0.0024), and was present in 56.4% of all rheumatic fever patients.

Preservation of left ventricular function during coronary artery bypass graft surgery.

Effects of hypothermic potassium cardioplegia on left ventricular performance and myocardial damage were assessed in 35 patients undergoing coronary artery bypass surgery. Hemodynamic data and enzymatic evidence of left ventricular ischemic damage were examined and compared in the immediate postoperative period. Left ventricular stroke work index showed a significant depression during the first hour with gradual recovery and a significant increase after 24 h. Myocardial specific isoenzyme creatine kinase (CK-MB) showed a very good nonlinear relationship with stroke work index within the whole range, whereas lactate dehydrogenase isoenzyme (LDH-I) had no relationship with the stroke work index. There was a high incidence of transient postoperative arrhythmias and electrical activity took a long time to stabilize. Left ventricular ultrastructure was generally well preserved. The results of this study demonstrate adequate structural and functional preservation of left ventricle by hypothermic potassium cardioplegia.

Antibodies to a streptococcal cell wall adjuvant structure persist in patient with chronic rheumatic heart disease.

Sera from 50 patients with chronic rheumatic heart disease were analysed by an enzyme linked immunosorbent assay for the presence of antibodies to the streptococcal minimal adjuvant moiety, muramyl dipeptide (MDP). The T-cell responsiveness to this structure was also studied in vitro, using the lymphocyte transformation test. Fifty four percent of the patients possessed anti-MDP antibodies in their sera when examined 5 to 25 years after the initial rheumatic attack. Such antibodies were found only in 5 to 6% of sera from healthy controls or from patients with cardiac disease of non-rheumatic origin. There was neither antigenic nor mitogenic stimulation by MDP of the T-cells from peripheral blood of chronic rheumatic heart disease patients or controls. The results point to a lifetime persistence of anti-MDP antibodies in rheumatic fever and rheumatic heart disease. Possible mechanisms by which detectable levels of such antibodies are maintained in rheumatic heart disease are discussed.

Chronic severe aortic regurgitation: a prospective follow-up of 60 asymptomatic patients.

Sixty asymptomatic patients (age 26 +/- 10 years) with chronic severe aortic regurgitation were followed prospectively for 2.4 +/- 1.4 years. Based on previous echocardiographic end-systolic dimension (ESD) and angiographic ejection fraction (EF) correlations, the cohort was divided into group A (21 patients) with ESD greater than or equal to 48 mm and group B (39 patients) with ESD less than 48 mm. Group B had a faster ESD progression (NS) and 19 crossed over to group A. Thirteen patients, all with ESD greater than 48 mm, reached designated end points. One died of cerebral embolism and 12 (age 31.4 +/- 10.6 years) required aortic valve replacement (AVR). Of these, 9 of 12 were asymptomatic and 11 of 12 had significant left ventricular dysfunction (LVD). The preoperative ESD of 51.9 +/- 4.1 mm fell to 38.4 +/- 3.6 mm (p less than 0.001) postoperatively and the EF of 43.7 +/- 4.16 increased to 64.9 +/- 5.9 (p less than 0.001). We found (1) the progression was faster than in other series; (2) ESD greater than 48 mm was associated with significant progression; and (3) patients with EF above 40% showed no residual LVD after AVR.

Complete hemodynamic evaluation of patients with aortic regurgitation by outpatient right heart catheterization and digital subtraction angiography.

The aim of this study was to demonstrate that total hemodynamic evaluation of patients with aortic regurgitation can be performed on an outpatient basis by combining right heart catheterization with digital subtraction angiography (DSA). Thirteen patients with severe aortic regurgitation were catheterized as outpatients, without premedication. The pulmonary artery was entered percutaneously through the femoral vein. Cardiac output and stroke volume were measured by the indicator dilution method by injection into the inferior vena cava and sampling from the pulmonary artery. The regurgitant fraction was obtained by subtracting the indicator stroke volume from the angiographic left ventricular stroke volume. The following results are expressed as mean +/- SD. Ejection fraction (%) = 54 +/- 6; end diastolic volume index (ml) = 228 +/- 40; end systolic volume index (ml) = 198 +/- 51 and regurgitant fraction (%) = 59 +/- 7 while the pulmonary wedge pressure (mmHg) = 10 +/- 3. In 4 cases, comparison with recent catheterization data showed good agreement for all parameters (r = 0.90), except ejection fraction (r = 0.75). In conclusion, this simplified catheterization method using digital subtraction enables the procedure to be done on an outpatient basis. All essential hemodynamic data can be obtained by right heart catheterization.

Immunoglobulin isotype response to the group-A streptococcal carbohydrate in humans.

We used an ELISA to determine the levels of specific anti-GAS carbohydrate IgG, IgM and IgA in 34 patients with acute rheumatic fever (ARF) with or without carditis, in 15 patients with acute glomerulonephritis (AGN) and in 18 control patients with noncomplicated GAS pharyngitis. Patients with ARF and AGN showed a significantly higher geometric mean titer as well as a higher frequency of elevated Ig of the IgG, IgM and IgA A-CHO class antibodies during the acute stage of this disease, when compared to controls. The IgM and IgA geometric means of the antibody were higher in ARF with carditis patients as compared to the non-carditis or AGN patients; however, the differences were not significant. In addition a lower frequency of antibody decline was observed in ARF with carditis patients who were seen in follow-up after a 1-year period, supporting previous observations of the persistence of this antibody in patients with rheumatic heart disease.

Inotropic effects of ionic and nonionic contrast materials in isolated heart preparations.

The inotropic effects of ionic (amidotriazoate) and nonionic (iohexol) contrast material were compared in isolated rat heart preparations. Left atria exposed to amidotriazoate for 10 mins exhibited a dose dependent depression of contractile force approximately twice as large as that brought about by equiosmolar sucrose. When the driving rate was reduced from 60 to 20 beats/min, this specific effect was abolished. The spontaneously beating hearts perfused with amidotriazoate-containing medium had increased resting tension and depressed force of contractions. These effects tended to spontaneously normalize. Upon bolus administration of amidotriazoate the contractile force of perfused hearts was briefly depressed and heart rate, action potential duration and time to peak force decreased. Iohexol did not produce any significant changes in the contractile force. The experiments illustrated direct action of ionic contrast dye on cardiac inotropy probably resulting from an immediate, slowly compensated ionic imbalance, and demonstrated a definite superiority of the nonionic contrast material.