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Biomedical subjects

J L Anderson

Publications and source records attributed to J L Anderson.

At least 235 records · Page 13Linked to original sources
PubMed1987

Efficacy of recainam, a new antiarrhythmic drug, for control of ventricular arrhythmias.

The antiarrhythmic efficacy and safety of oral recainam hydrochloride, a newly synthesized compound, were assessed during a 2-part study of 12 patients with frequent (at least 30/hour) ventricular premature complexes (VPCs). During the initial dose-ranging phase, 11 patients with qualifying arrhythmias (median VPC frequency 575/hour, range 37 to 1,494) received incremental oral doses of 100, 300 and 500 mg of recainam given every 8 hours, each for 3 days. Efficacy was assessed on the last day of each dose. The 300-mg/day dose of recainam was generally ineffective; the 900-mg/day dose was partially effective (58% median VPC reduction, p = 0.03); and the 1,500-mg/day dose was very effective (79% reduction, p less than 0.003). Median reductions in repetitive beats (beats in couplets and runs) for the 3 doses were 18% (difference not significant), 94% (p less than 0.01), and 98% (p less than 0.004), respectively. Recainam provided individual efficacy (at least 70% VPCs or at least 90% repetitive beat suppression, or both) in 7 (64%) of the patients taking 900 mg/day and in 8 (73%) taking 1,500 mg/day. Minimum steady-state plasma concentrations were higher in responders (1.8 +/- 0.5 microgram/ml) than in nonresponders (1.0 +/- 0.5 microgram/ml) (p less than 0.05). The electrocardiographic response to recainam (1,500 mg/day) included increases in PR (by 22%, p less than 0.003) and QRS (by 14%, p less than 0.002) intervals and a small decrease in JTc duration (by 9%, p less than 0.04). Radionuclide ejection fraction did not change. Noncardiac adverse reactions were minimal.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1987

Duration of effects and tolerance of slow-release isosorbide-5-mononitrate for angina pectoris.

Isosorbide-5-mononitrate (IS-5MN) is an active metabolite of isosorbide dinitrate, but unlike its parent compound, is nearly 100% bioavailable after oral administration. Once-a-day therapy with a slow-release formulation of IS-5MN is used widely in Europe for 24-hour prophylaxis of angina pectoris. In a randomized, crossover, double-blind, placebo-controlled study, the duration of effects of 50 and 100 mg of slow-release IS-5MN were evaluated after the first dose and after once-a-day therapy for 1 week in 9 patients with stable angina pectoris. Compared with placebo values, standing blood pressure decreased (p less than 0.001) and exercise time to the onset of angina and total exercise duration increased (p less than 0.008 and p less than 0.003) at 4 hours, but not at 20 or 24 hours after first dose of 50 and 100 mg of slow-release IS-5MN. After once-a-day therapy for 1 week, no improvement in exercise duration or reduction in ST-segment depression was seen after 50 or 100 mg of slow-release IS-5MN at 4, 20 or 24 hours despite high plasma IS-5MN concentrations. Thus, despite therapeutic plasma concentrations, 50 and 100 mg of slow-release IS-5MN did not exert antianginal or anti-ischemic effects at 20 and 24 hours after the first dose and at 4, 20 and 24 hours after sustained once-a-day therapy for 1 week.

Adult↗
PubMed1987

The disposition of recainam hydrochloride during and after intravenous loading and maintenance infusion in cardiac patients.

Recainam hydrochloride is a newly synthesized propylurea compound demonstrating potent antidysrhythmic effects. Recainam was administered as a loading dose of 3 mg/kg/40 minutes followed by a continuous infusion of 0.9 mg/kg/hr for 23 hours and 20 minutes to ten patients with cardiac disease and frequent PVCs (more than 30/hr). A total of 15 plasma samples were drawn over 36 hours during and after the infusion. Plasma recainam concentration was determined by high performance liquid chromatography (HPLC). The mean (+/- SD) postload and 24-hour plasma concentrations were 5.19 +/- 0.51 and 3.41 +/- 0.71 micrograms/mL, respectively. The data were best described by a two-compartment model yielding the following mean (+/- SD) pharmacokinetic parameters: lambda 1 = 2.62 +/- 0.68 hr-1, lambda 2 = 0.144 +/- 0.014 hr-1, t1/2 lambda 2 = 4.84 +/- 0.46 hr, CLT = 0.268 +/- 0.057 L/hr/kg, CLR = 0.143 +/- 0.052 L/kg/hr, CLNR = 0.125 +/- 0.041 L/hr/kg, Vdss = 1.3 +/- 0.19 L/kg, and Vd lambda 2 = 1.9 +/- 0.43 L/kg. There were no adverse reactions. Based on these data, recainam can be safely administered as a loading dose followed by a continuous infusion in patients with stable cardiac disease without significant ventricular dysfunction.

Adult↗
PubMed1987

Predictive value of immunofluorescence and electron microscopic evaluation of endomyocardial biopsies in the diagnosis and prognosis of myocarditis and idiopathic dilated cardiomyopathy.

The distinction between idiopathic dilated cardiomyopathy and myocarditis is controversial, both clinically and pathologically. To increase diagnostic accuracy and provide prognostic information, we prospectively tested the routine application of immunofluorescence and electron microscopy in endomyocardial biopsy evaluation. Biopsy samples from a consecutive series of 79 patients with cardiomyopathy and possible myocarditis were thus evaluated by light (LM), immunofluorescence (IF), and electron microscopy (EM). Patient course was followed prospectively to determine prognostic factors. Immunoglobulin (IgG) and complement (C) in biopsy tissue were graded 0 to 3+ and an IF score was derived as 2 (IgG) grade + C grade. A highly significant association was found between IF score greater than or equal to 2 and the presence of mononuclear cells (lymphocytes plus macrophages) greater than 5/high-power field, confirmed by EM; 12 of 15 (80%) with IF score greater than or equal to 2 had inflammatory cells, vs only 2 of 64 (3%) with IF score less than 2 (p less than 0.000001). EM was used to confirm the identity of infiltrating cells and to grade myofilament loss (0 to 3+) and 11 other ultrastructural features. EM did not provide important predictive information in myocarditis, but confirmed the presence of inflammatory cells. However, the EM finding of myofilament loss provided prognostic information both in patients with and without myocarditis (p less than 0.03). Mortality at 18 months was 37% for patients with 2 to 3+ myofilament loss, vs 10% in those with 0 to 1+ loss. Moreover, myofilament loss was prognostically independent of clinical class and ejection fraction. EM determination of myofilament loss is valuable as a prognostic indicator, whether or not myocarditis is present. Routine IF and EM increase the diagnostic accuracy and prognostic information in endomyocardial biopsies from patients with suspected myocarditis or cardiomyopathy.

Adolescent↗
PubMed1987

Long-term experience with sotalol in the treatment of complex ventricular arrhythmias.

Sotalol was given for extended therapy to 22 of 29 patients with frequent (greater than or equal to 30/hour) complex premature ventricular complexes (PVCs) who had participated in a short-term study of sotalol vs placebo. Open-label sotalol was given in individually titrated divided doses of 160 to 800 mg/day (median 323, mean 386 mg/day). Response was assessed at approximately 1, 6, and 12 months or until patient discontinuation. The period of sotalol therapy averaged 9 months (range, 0.2 to 22.7). At about 1 month, 13 (59%) of 22 patients showed effective control of arrhythmia. The median percentage change in total PVCs for individual patients at 1 month was -70% and for repetitive PVCs it was -95%. At about 6 months, 10 (45%) of the 22 patients continued to be successfully treated; at about 12 months, seven patients continued on sotalol, six (27%) successfully treated according to Holter criteria. Reasons for discontinuation included lack of efficacy in nine, adverse effects in four (fatigue in three, bradycardia with sinus pauses in one), and miscellaneous reasons in two. ECG PR and especially QTc intervals increased significantly during therapy (p less than 0.02, p less than 0.01, respectively). In summary, sotalol is a moderately effective antiarrhythmic agent in patients with complex PVCs, but during long-term therapy a rather high dropout rate was observed because of arrhythmia recurrence or adverse effects.

Administration, Oral↗
PubMed1987

Occurrence of exercise-induced and spontaneous wide complex tachycardia during therapy with flecainide for complex ventricular arrhythmias: a probable proarrhythmic effect.

Flecainide acetate, a new antiarrhythmic agent, possesses favorable pharmacokinetic and hemodynamic properties and demonstrates highly favorable antiarrhythmic activity in patients with ventricular arrhythmias. However, the proarrhythmic potential of flecainide deserves further evaluation. In 7 (13%) of 55 consecutive patients treated with oral flecainide, 200 to 600 mg/day, for complex ventricular arrhythmias (including sustained ventricular tachycardia in 14), we observed the appearance of new or more sustained exercise-induced (five patients) or spontaneous (two patients) wide complex tachycardia. The mechanism of wide complex tachycardia appeared to be ventricular tachycardia in all seven. In our series, episodes were self-remitting or successfully treated. In four patients, wide complex tachycardia did not recur during exercise testing during alternative antiarrhythmic therapy (three patients) or no antiarrhythmic therapy (one patient). These observations raise the possibility of flecainide-related proarrhythmia, manifested as an increased propensity to exercise (activity)-induced wide complex tachycardia, which was not reliably predicted by results of Holter recordings or programmed electrical stimulation. Patients with complex ventricular arrhythmias beginning long-term treatment with oral flecainide should be considered for treadmill exercise testing together with ambulatory monitoring as part of the initial assessment of drug efficacy.

Adult↗
PubMed1987

Efficacy and safety of sustained (48 hour) intravenous infusions of milrinone in patients with severe congestive heart failure: a multicenter study.

Milrinone is a new bipyridine inotrope that has shown promise in initial clinical testing when administered intravenously or orally. The present multicenter study was designed to evaluate the clinical effectiveness and safety of sustained (48 hour) intravenous infusions of different doses of milrinone, as would be used clinically, in a controlled fashion using invasive hemodynamic monitoring. Entry was limited to adult patients with chronic heart failure of functional class III or IV, with a cardiac index less than or equal to 2.5 liters/min per m2 or a pulmonary capillary wedge pressure greater than or equal to 15 mm Hg, or both. After stable baseline hemodynamic recordings were obtained, milrinone was given as loading (microgram/kg per 10 min) and maintenance infusions (microgram/kg per min) to 189 patients in one of four loading/maintenance dosage regimens: 37.5/0.375 (low dose, n = 26), 50/0.50 (intermediate dose, n = 95), 75/0.75 (high dose, n = 15) and 50/0.25 (lowest dose, n = 53). The lowest dose was shown to be ineffective for maintenance therapy. Effective individual patient responses were defined as greater than or equal to 20% increase in cardiac index or decrease in pulmonary capillary wedge pressure, or both. During early therapy (less than or equal to 3 hour), 99% of patients showed an effective maximal response, and 90% an effective mean response. An effective mean response was observed during days 1 and 2 in 80% of patients, with a positive dose-response trend (69% response, low dose; 80%, intermediate dose; 93%, high dose; day 1). Each loading regimen was effective, with maximal mean response occurring at 15 minutes. Cardiac index initially increased by an average of 24 to 42% for all patients in the three groups, whereas pulmonary capillary wedge pressure decreased by 24 to 33%. Initial decreases in systemic vascular resistance averaged 15 to 31%. Initial changes in heart rate (+4 to +13%) and mean arterial pressure (-2 to -13%) were modest. Significant mean hemodynamic responses were maintained over the 48 hours. Increases in cardiac index for days 1 and 2 averaged 38 and 39% for those completing constant low dose drug, 34 and 37% for intermediate dose and 73 and 44% for high dose. Decreases in pulmonary capillary wedge pressure for all patients averaged 18 to 32% on days 1 and 2, with little dose response. Heart rate changes were modest and variable, averaging -9 to 9%.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1987

Development and evaluation of anisoylated plasminogen streptokinase activator complex (APSAC) as a second generation thrombolytic agent.

Anisoylated plasminogen streptokinase activator complex (APSAC) was developed as a second generation thrombolytic agent in an attempt to overcome some of the limitations to the intravenous application of streptokinase for coronary artery thrombolysis. Temporary protection of the active site on the plasminogen molecule by acylation allows APSAC to be given by rapid injection, confers semiselectivity for clot (at lower doses) and prolonged fibrinolytic action. These properties may simplify intravenous administration, improve coronary reperfusion response and reduce reocclusion potential. Clinical trials with APSAC, still ongoing, allow the following tentative conclusions: the efficacy of intravenous APSAC appears to be equivalent to that of intracoronary streptokinase, when given within 4 hours of the onset of symptoms of myocardial infarction, and superior to that of intravenous streptokinase, but it is easier to administer. Early APSAC therapy leads to reperfusion rates of 60 to 65% and patency rates of 70 to 80%. Early reocclusion rates (within 24 hours) appear to be as low as or lower than those obtained with other agents. Bleeding complications and allergic manifestations after APSAC are acceptably low and comparable with those of equivalent doses of streptokinase. The potential for mortality benefit after APSAC appears to be high and is undergoing additional study. Thus, APSAC therapy, which can be given by simple injection over 2 to 5 minutes, appears promising as a future first line approach to reperfusion therapy in acute myocardial infarction.

Animals↗
PubMed1987

Recent clinical developments in thrombolysis in acute myocardial infarction.

Intracoronary streptokinase can accomplish reperfusion in 70 to 75% of patients with acute myocardial infarction (AMI), and intravenous streptokinase in approximately 50% of those with prior documented coronary occlusion. The time constraints for accomplishing significant myocardial salvage have proved to be quite restrictive, however. Studies in which treatment has begun after an average of 4 hours of symptoms have not shown significant improvement in ventricular function. In contrast, those in which intervention has been applied earlier, particularly in less than 2 to 3 hours, have consistently shown benefit. The price for applying thrombolytic therapy includes the risk of severe bleeding (about 5%) but, fortunately, mortality as a result of bleeding has been rare (less than or equal to 0.5%). Reperfusion may be only transient or incomplete (and insufficient). An early reocclusion rate of about 15 to 20% has been commonly noted, in fact. Recently, major studies have pointed to a reduction in early mortality in patients treated early (within about 3 hours) after the onset of symptoms. Much interest is now being focused on developing safer, more effective thrombolytic agents such as tissue plasminogen activator and anisoylated plasminogen streptokinase activator complex (APSAC). Adjunctive therapy with coronary angioplasty is also being applied. In the judgement of many, reperfusion therapy may represent the greatest advance in the approach to AMI of the current decade.

Clinical Trials as Topic↗
PubMed1987

Reperfusion in acute myocardial infarction. A multicentre randomised trial of early intracoronary streptokinase and intravenous anisoylated plasminogen streptokinase activator complex in the United States.

To compare the reperfusion potential of anisoylated plasminogen streptokinase activator complex (APSAC), administered intravenously, and intracoronary streptokinase (the accepted standard for comparison in the United States), a randomised multicentre reperfusion trial was undertaken in the United States. A preliminary evaluation of results was made, based on the first 93 patients. Patients with acute myocardial infarction were studied angiographically, and those with coronary occlusion grade 0 or 1 were randomised and treated within 6 hours from symptom onset (mean 3 hours 25 minutes) with intracoronary streptokinase (20,000U bolus, then 2000 U/minute), or APSAC (30U over 2 to 4 minutes). Reperfusion was defined by a blinded reader as grade 2 or 3 flow after 90 minutes. Entry characteristics of patients in the 2 groups were comparable. Reperfusion rates were similar [19/39 (49%) of evaluable streptokinase patients and 19/43 (44%) of APSAC patients] and were dependent on the initial occlusion grade [38% of patients with grade 0 (streptokinase = 10/27, APSAC = 13/34), but 71% of patients with grade 1 (9/12, 6/9, respectively); p less than 0.02]. Grade 1 occlusion was present in 30% of patients treated within 4 hours, versus 16% treated at over 4 hours (p = 0.3). APSAC as a 2 to 4 minute infusion was well tolerated, and the change in mean blood pressure was minor (-6 mm Hg). Thus, APSAC and streptokinase provide similar reperfusion results, but APSAC is easier to administer, and shows excellent haemodynamic tolerance.

Adult↗
PubMed1987

Acute coronary occlusion and reperfusion. Reliability of angiographic classification and grading.

93 patients with acute myocardial infarction entered into a multicentre, randomised fibrinolytic therapy study underwent coronary angiography prior to treatment with intracoronary streptokinase or intravenous anisoylated plasminogen streptokinase activator complex (APSAC). Subsequent to administration of fibrinolytic therapy, coronary arteriography of the infarct-related artery was also performed at 15, 30, 45, 60, 75 and 90 minutes. Angiographically defined coronary perfusion was graded as follows: grade 0--no perfusion; grade 1--vessel penetration by contrast without perfusion; grade 2--partial perfusion with delayed flow and/or clearance; grade 3--normal flow and clearance. Two independent readers at separate sites reviewed all serial angiograms with consensus achieved with a third reader. Disagreement potentially affecting therapeutic outcome (grades 1 vs 2, 0 vs 2, 0 vs 3, and 1 vs 3) occurred for only 15 angiographic views. Evaluation of agreement by the K index demonstrated a reasonable level of agreement for all grades (K = 0.73). In order to assess the effect of angiographic classification and timing upon reperfusion percentage rates, 4 reperfusion criteria were applied to these serial angiograms: group A = grade 2 or 3 flow at 90 minutes; group B = grade 2 or 3 flow at any time; group C = grade 1, 2 or 3 flow at any time in patients with control grade 0 or 1 flow; group D = grade 1, 2 or 3 flow at any time in patients with only grade 0 flow at control. Percentage reperfusion varied widely depending upon reperfusion criteria: group A: streptokinase 49%, APSAC 44%; group B: streptokinase 70%, APSAC 50%; group C: streptokinase 86%, APSAC 67%; group D: streptokinase 79%, APSAC 59%.(ABSTRACT TRUNCATED AT 250 WORDS)

Anistreplase↗
PubMed1987

Electrocardiographic and enzymatic infarct size in a randomised study of intracoronary streptokinase and intravenous anisoylated plasminogen streptokinase activator complex in acute myocardial infarction.

The effect of thrombolytic therapy on ECG and enzymatic indices, including estimates of relative infarct size, was studied in 93 patients with acute myocardial infarction randomised to intracoronary streptokinase or intravenous anisoylated plasminogen streptokinase activator complex (APSAC) therapy within 6 hours of the onset of symptoms. 90 minutes after treatment, 49% (19/39) of the evaluable streptokinase patients and 44% (19/43) of the APSAC patients had reperfused (p = NS). The time from treatment to reperfusion was less in the streptokinase patients (30 +/- 18 minutes for streptokinase and 42 +/- 22 minutes for APSAC, p less than or equal to 0.02). Resolution of ST segment elevation, 90 minutes after treatment, was greater in the streptokinase patients (residual ST segment elevation 47 +/- 36% of initial value for streptokinase and 70 +/- 49% for APSAC, p less than or equal to 0.06) and in the patients reperfused by either agent (residual ST segment elevation 46 +/- 34% for reperfused and 68 +/- 52% for non-reperfused, p less than or equal to 0.10). ECG infarct size at discharge, determined by sum of Q waves and a 29-point QRS score, relative to the degree of initial ST segment elevation was similar in the streptokinase and APSAC patients, but smaller in reperfused than non-reperfused patients (p less than or equal to 0.01 for sigma Q). Peak serum creatine kinase and MB isoenzyme of creatine kinase levels were similar in the streptokinase and APSAC, and in reperfused and non-reperfused patients. Lower peak lactic acid dehydrogenase and especially lactic acid dehydrogenase isoenzyme values (by 16% and 22%, respectively) were observed in reperfused patients, but differences did not achieve significance. However, the time to peak enzyme levels was significantly shorter in the reperfused patients. Early intracoronary streptokinase and intravenous APSAC therapy have similar effects on ECG and enzymatic infarct size. Reperfusion by either agent, given at a mean of 3 hours 25 minutes, may reduce estimates of infarct size modestly.

Adult↗
PubMed1987

Biologic rhythm disorders, depression, and phototherapy. A new hypothesis.

Disturbances of the circadian timing system are implicated in the pathogenesis of numerous clinical syndromes, including sleep and affective disorders. Abnormalities of circadian rhythms can now be directly measured in the clinical laboratory and potentially corrected. Sleep scheduling disorders are most commonly due to phase misalignments between the endogenous circadian pacemaker and the socioenvironmental schedule. Current research is increasing our understanding of the influence of bright light exposure on the circadian timing system and has begun to be used successfully in the management of these conditions. There is substantial evidence that abnormalities of the circadian timing system are associated with depression. However, the application of new biologic rhythm diagnostic techniques would be required to establish whether circadian dysfunction is involved in the pathogenesis of these conditions. We propose a new hypothesis that phototherapy for seasonal depression may act by increasing an abnormally low circadian amplitude in those patients, such as that reported in endogenously depressed patients. The powerful effect of light on the circadian system indicates that phototherapy may become an important tool in the management of disorders of circadian etiology.

Circadian Rhythm↗
PubMed1986

Initial and long-term outpatient experience with pirmenol for control of ventricular arrhythmias.

Pirmenol, a new class IA antiarrhythmic agent, has shown promise in short-term trials, but long-term efficacy has not been documented. We thus evaluated 11 patients with frequent (greater than or equal to 60/h) premature ventricular complexes (PVC) given oral pirmenol for 25-727 days. Ten of 11 patients entering the long-term open trial had shown greater than or equal to 70% (mean 83%) PVC suppression during in-hospital pirmenol dose ranging. Long-term pirmenol was given in divided doses of 100-600 mg/day. Mean PVC frequency during baseline was 13,078/24 h (range, 3,218-32,718); couplets averaged 481/24 h (1-2,829) and runs 45/24 h (0-334). Ambulatory monitoring was performed at 1, 3, 6, and 12 months, then semiannually. Mean absolute PVC suppression at 1 month averaged 75% (p less than or equal to 0.02). Median individual percentage PVC suppression was 94%. During the first 3 months, 8 patients (73%) continued to show a favorable response (greater than or equal to 70% suppression), and 3 had arrhythmia recurrence and were dropped. One responder was withdrawn after the onset of paroxysmal atrial fibrillation, and another early responder was withdrawn after 3 months because of arrhythmia relapse. Six patients have been treated for over 1 year, with 99% mean PVC suppression. Mean couplet and run frequencies at 1 month decreased by means of 76% (p less than or equal to 0.05) and 92% (p = 0.001) respectively. At 1 year, couplets were suppressed 99.8% and runs by 99.7% in the 6 patients remaining on pirmenol.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Occurrence of ventricular arrhythmias in patients receiving acute and chronic infusions of milrinone.

Milrinone is a promising new inotrope, but its arrhythmogenic potential has not been defined. We monitored ventricular arrhythmias during a 24-hour baseline and 48-hour milrinone infusion period in 12 patients with chronic heart failure. Patients were characterized by a mean age of 58 years and a left ventricular ejection fraction of 21%. Nine (75%) were male, nine had primary idiopathic dilated cardiomyopathy, and three had coronary artery disease. None had a history of cardiac arrest or sustained ventricular tachyarrhythmia. Milrinone was given as a loading dose (mean 53 micrograms/kg/10 min; range 37.5 to 75) followed by a 48-hour maintenance infusion (mean 0.53 micrograms/kg/min; range 0.25 to 0.75). Acutely, cardiac index increased by 27% and pulmonary wedge pressure decreased by 30% during milrinone; changes were maintained during continued therapy. Ventricular arrhythmia response was variable, with no significant overall difference. However, a trend toward increased ectopic activity was noted. No sustained tachyarrhythmias occurred. Mean frequency of premature ventricular complexes (PVCs) was 87 +/- 48 PVCs/hr (x +/- SEM) during baseline monitoring and 141 +/- 69/hr following infusion of the drug (p = 0.08). Mean frequency of couplets was 6.0 +/- 4.9/hr before drug infusion and 14.3 +/- 11.0/hr during infusion (p = 0.21). Mean frequency of runs was 0.9 +/- 0.8/hr before and 2.7 +/- 2.4/hr during drug infusion (p = 0.29). Two patients met criteria for proarrhythmia (increased PVCs of greater than 4x and/or repetitive forms of greater than 10x. However, neither proarrhythmia patient required reduction in the dosage of milrinone or additional antiarrhythmic therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

HLA-DR typing and lymphocyte subset evaluation in rheumatic heart disease: a search for immune response factors.

Several autoimmune diseases have been associated with increased frequencies of specific histocompatibility (HLA) antigens, particularly for the D (DR) locus, that may be linked to immune response genes. Rheumatic valvular heart disease (RHD) has been postulated to have autoimmune features, but HLA associations have not been established. We, therefore, performed HLA-DR typing in 33 consecutive patients with RHD and in 82 normal blood bank control subjects. We also evaluated the frequencies of lymphocyte subsets by means of monoclonal antibodies and immunofluorescence flow cytometry and made functional correlations for the natural killer cell (NKC) in patient subsets. The DR patterns in RHD were heterogeneous. However, significant differences were noted for DR4 and DR6. DR4 was present in 52% (17 of 33) of RHD patients vs 32% (26 of 82) of control subjects (p less than 0.05). DR6 was present in 6% (2 of 33) of patients vs 26% (21 of 82) of control subjects (p less than 0.02). The associated relative odds of DR4 was 2.3 and the etiologic fraction was 0.30. The relative odds of DR6 was 0.19 and the preventive fraction was 0.21. A distinct clinical profile was not associated with DR4 positivity or DR6 negativity. The frequency of lymphocyte subsets was not significantly changed except for OKT8. Median NKC numbers tended to be higher in RHD patients than in control subjects (p less than 0.05). In contrast, NKC functional activity tended to be lower in RHD; median lymphocyte to target cell (K562 line) ratio resulting in 50% killing (L/T 50) was 20.5 in RHD patients vs 11.5 in control subjects (p = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗