Antimurine antibody to OKT3 in cardiac transplantation: implications for prophylaxis and retreatment of rejection.
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Animals↗
Biomedical subjects
R L Menlove
Publications and source records attributed to R L Menlove.
Clinical manifestations of vascular rejection in cardiac transplantation.
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Adult↗
Utility of surgical margins in the radiotherapeutic management of soft tissue sarcomas.
Seventy-four adult patients with localized soft tissue sarcomas were treated with radiation therapy following surgery between 1965 and 1988. Fifty-three were treated after the first excision of their tumor with 6 (11.3%) local recurrences. Twenty-one received radiation after excision of recurrent disease with 11 (52.4%) local failures (P less than .0005). Metastatic disease occurred in 14 (26.4%) of the primary tumors and 8 (38.1%) with multiple previous excisions (P less than .48). Of those patients treated for primary sarcoma, there were no local failures with pathologically wide margins or if a single margin was microscopically positive. Local failure occurred in 4 of 26 (15.4%) if the tumor was merely enucleated and in 2 of 11 (18.2%) who had grossly positive surgical margins (P not significant). Local failure was also more common in truncal locations (33.3%) as compared with extremity locations (8.7%, P = .1359). Additional factors analyzed which adversely affected prognosis included tumor grade, stage, and inadequate radiation dose.
Adult↗
A randomized trial of the immunosuppressive efficacy of vincristine in cardiac transplantation.
We evaluated the efficacy of the addition of the lymphoblasticidal agent vincristine to standard immunosuppression in heart transplantation in a prospective randomized study of 92 patients (46 to receive and 46 to not receive vincristine) with a follow-up period of 12 months. Patients received either equine antithymocyte globulin for the first week or OKT3 monoclonal antibody (OKT3) for the first 10 or 14 days after transplantation. Six to eight doses of vincristine were given over 9-12 weeks, beginning 2 days after completion of ATG or OKT3. The number of rejection episodes in the first six months posttransplantation, the percentage of patients corticosteroid maintenance-free at one year, cumulative immunosuppressive drug doses, deaths, infections, and neuropathy were followed. The addition of vincristine resulted in more patients achieving corticosteroid maintenance-free status at one year (vincristine 68%, no vincristine 38%, P = 0.01). In comparing patients at relatively high risk for rejection (those younger than 55 years and all females) with those at relatively low risk (males older than 55 years), only the high-risk vincristine-treated patients showed significantly fewer rejection episodes and a higher corticosteroid maintenance status at one year (66% vs. 32%, P = 0.01). There were no significant differences in survival (vincristine 96%, no vincristine 98%), infection, or amounts of other immunosuppressive agents used. The major side effect was neuropathy, which occurred more frequently in the vincristine-treated group (43% vs. 18%, P less than .001). We conclude that vincristine acts as an immunosuppressive agent in cardiac transplantation, particularly in patients at higher risk for rejection.
Cyclosporins↗
Relationship of OKT3 sensitization and vascular rejection in cardiac transplant patients receiving OKT3 rejection prophylaxis.
We prospectively and serially monitored plasma levels of OKT3 in 20 patients who were receiving 14- or 21-day rejection prophylaxis with OKT3. We retrospectively compared plasma OKT3 levels with biopsy scores assessed by light microscopy and immunofluorescence, clinical findings, human antimouse antibody (HAMA) production assessed by a blocking assay and by ELISA, and circulating immune complex levels assessed by a flow cytometric Raji cell assay. Using these methods, we evaluated the relationship of OKT3 sensitization, a humorally mediated immune response, to the development of vascular rejection in these patients. We found that 6 of 20 patients had declines in plasma OKT3 levels to less than 50% of their steady-state value before the conclusion of therapy (OKT3 consumption). This fall in plasma OKT3 preceded a significant rise in the CD 3 lymphocyte level by up to 3 days. All 6 patients showed HAMA production by either blocking or ELISA assay (P = less than 0.02) and developed vascular rather than cellular rejection (P = less than 0.01). OKT3 sensitization was significantly more common in patients treated with 21-day rejection prophylaxis (4 of 6 patients, P = less than 0.01). Only 4 of 14 other patients showed vascular rejection; 2 of these 4 also developed HAMA without OKT3 consumption and both had been treated with 21-day rejection prophylaxis with OKT3. None of the 20 patients showed significant levels of circulating immune complexes. This study demonstrates that OKT3 sensitization is strongly associated with vascular rejection. Vascular rejection was usually demonstrated 7 days after OKT3 consumption was seen and was coincident with HAMA production. By contrast, 4 patients without OKT3 sensitization had vascular rejection demonstrable in the early posttransplant period; in such patients, prospective immunofluorescence of biopsies was the only reliable indicator of this rejection type. The higher incidence of vascular rejection in these 20 patients was definitely related to the use of 21-day OKT3 rejection prophylaxis. Overall, 7 of the 12 patients treated with this regimen developed vascular rejection. Allograft and patient survival among patients with vascular rejection was significantly worse than in patients with cellular rejection (P = less than 0.01). Prospective monitoring of patients treated with OKT3 by serial plasma levels and by biopsy immunofluorescence will identify patients at risk for these types of humoral rejection.
Antibodies, Anti-Idiotypic↗
Spontaneous variability in ventricular ectopic activity during chronic antiarrhythmic therapy.
Previous determinations of variability in frequency of ventricular arrhythmias have been based on repeated recordings obtained in the absence of therapy. We evaluate variability during "effective" treatment with antiarrhythmic drugs. Variability in the percent suppression of premature ventricular complexes (PVCs) was determined in 55 patients with chronic arrhythmias who underwent multiple ambulatory electrocardiographic recordings during evaluation of chronic therapy with antiarrhythmic drugs initially determined to be effective, which was defined as 70% or more reduction in total PVC frequency or 90% or more reduction in repetitive forms. During chronic therapy, total PVCs were suppressed by 92%, averaged after a logarithmic transformation step, and repetitive beats were suppressed by 88%. Variability in suppression was substantial. The one-sided 95% confidence intervals required a fall in suppression of total PVCs to 40% or less to exceed limits of spontaneous variability and of repetitive PVCs to 66% or less. Suppression declined at least once during therapy to less than 60% for total PVCs in 24 of 55 patients (44%) and to less than 80% for repetitive PVCs in 13 of 33 patients (39%); nine patients (16%) showed increases in PVC frequency at least once to levels above pretreatment baseline. Seven subgroups were analyzed for their effects on variability and loss of suppression: age, gender, disease etiology, cardiac function, baseline PVC frequency, use of beta-blockers, and class of antiarrhythmic drug. Differences in confidence bounds and loss of suppression were found to be determined in a complex way by subgroup differences in variability and in initial levels of PVC suppression. Variability was greater for patient subgroups with greater PVC frequency, beta-blocker therapy, and non-coronary artery disease. However, clinical loss of suppression was more common only in more elderly patients and those with worse cardiac function. In summary, substantial variability in arrhythmia frequency occurs during effective antiarrhythmic therapy, and the 95% confidence limits of spontaneous variability are broad and determined in a complex way. Careful consideration should be given before concluding on the basis of a single Holter test that changes (increases) in arrhythmia frequency, especially in certain subgroups, are caused by treatment failure.
Adrenergic beta-Antagonists↗
Influence of corticosteroid-free maintenance immunosuppression on allograft coronary artery disease after cardiac transplantation.
Although the etiology of allograft coronary artery disease, a major limiting factor in long-term survival after cardiac transplantation, is poorly understood, it is undoubtedly in part immune mediated and not detected by routine endomyocardial biopsy. Therefore it is possible that withdrawal of maintenance corticosteroids, although providing other short- and long-term benefits, could increase the prevalence of allograft coronary artery disease by permitting undetected immune-mediated vascular injury to occur. To assess whether corticosteroid-free maintenance immunosuppression increased the prevalence of allograft coronary artery disease, we reviewed serial angiograms of 102 patients (49% not receiving corticosteroid maintenance therapy) who underwent heart transplantation after March 7, 1985. Multiple variables including serum cholesterol, recipient and donor age, sex, blood pressure, rejection frequency and severity, early rejection prophylaxis protocol (polyclonal versus monoclonal T-cell agents), and corticosteroid use were examined in relation to allograft coronary artery disease by univariate and multivariate analyses. Allograft coronary artery disease was identified in 21 patients (seven severe, four moderate, and 10 mild). The prevalence by Kaplan-Meier life-table analysis was 17% at 1 year and 25% at 2 years. No further allograft coronary artery disease was detected among patients undergoing angiography at three years. Increased allograft coronary artery disease was not noted in patients withdrawn from maintenance corticosteroids when compared with their corticosteroid-requiring counterparts. In fact, with each 1 gm increment in cumulative corticosteroid use, a slightly increased risk (1.04, p less than 0.05) of allograft coronary artery disease was noted (Cox regression model). None of the other variables correlated with the prevalence of allograft coronary artery disease. Thus withdrawal of maintenance corticosteroids is not associated with an increased risk of early allograft coronary artery disease and minimization of corticosteroids may lead to a decreased long-term incidence of coronary artery disease in cardiac transplant recipients.
Adrenal Cortex Hormones↗
Long-term effect of almitrine bismesylate in patients with hypoxemic chronic obstructive pulmonary disease.
A long-term evaluation of the therapeutic efficacy and safety of oral almitrine bismesylate (AB) (50 mg twice daily) was made on 25 patients with COPD and moderate hypoxemia residing at an altitude of 1,500 m in a double-blind placebo-controlled study. Thirteen patients receiving AB (baseline PaO2, 54.3 +/- 4.9 mm Hg; mean +/- SD) and 12 patients receiving placebo (baseline PaO2, 53.0 +/- 4.1 mmHg) were periodically followed by arterial blood gas and other pulmonary function studies and plasma levels of AB. Eight patients receiving AB and nine patients receiving placebo were followed for 1 yr; all patients were followed for at least 90 days. AB administration resulted in an increase in PaO2 to 62.2 +/- 9.3 mm Hg (p less than 0.01) on Day 28. The increase was maintained until Day 360 (63.8 +/- 4.6 mm Hg; p less than 0.01). The mean plasma concentration of AB on Day 28 was approximately one-half that on Day 90 when the plasma level reached a near maximum. AB was associated with weight loss (five of 13 patients receiving AB lost more than 10% of their baseline body weight) and peripheral paresthesias of the lower extremities (three patients), both occurring at the peak plasma levels of the drug. We conclude that AB causes a long-term improvement in arterial oxygenation in hypoxemic patients with COPD residing at an altitude of 1,500 m. Our data suggest that lower doses of AB might produce the same effect on PaO2 with less adverse associated effects, and this should be tested in future studies.
Adult↗
A prospective comparison of murine monoclonal CD-3 (OKT3) antibody-based and equine antithymocyte globulin-based rejection prophylaxis in cardiac transplantation. Decreased rejection and less corticosteroid use with OKT3.
To test the efficacy of murine monoclonal CD-3 antibody (OKT3) in early prophylaxis for cardiac allograft rejection, we conducted a 6-month trial, prospectively assigning 51 patients to receive either equine antithymocyte globulin-based (n = 25) or OKT3-based (n = 26) early prophylaxis. ATG patients received 8 days of ATG (10 mg/kg), with the first dose given preoperatively. OKT3 patients received 14 days of OKT3 (5 mg) beginning on the second postoperative day. Corticosteroid and azathioprine administration were similar during early prophylaxis. Cyclosporine was begun preoperatively in ATG patients and on the fourth postoperative day in OKT3 patients. In addition, patients in both groups were randomized to receive or not receive eight weekly administrations of vincristine (0.025 mg/kg). While infection rate (0.8 +/- 0.2 infections/patient in both groups [mean +/- SEM]) and mortality (1 patient in each group) did not differ, OKT3-based early prophylaxis delayed the first rejection episode (76 +/- 11 days vs. 36 +/- 8 days, P = 0.005) and decreased the risk of rejection during the 6-month follow-up (P less than 0.001, product-limit analysis). Overall, the OKT3 group manifested 1.5 +/- 0.2 episodes of rejection/patient compared with 2.2 +/- 0.2 episodes/patient in the ATG group (P = 0.036). Despite similar 6-month cumulative cyclosporine and azathioprine dosages, six month average corticosteroid administration was less in the OKT3 group (12.2 +/- 1.5 mg prednisone equivalent/m2/day versus 19.3 +/- 2.1 mg prednisone equivalent/m2/day, P = 0.008), fewer OKT3 patients subsequently required additional cytolytic therapy for rejection (2 [8%] versus 12 [48%], P = 0.001), and more patients in the OKT3 group were successfully weaned off maintenance corticosteroids (22 [88%] versus 11 [46%], P = 0.002). We conclude that, relative to an equine ATG-based protocol, OKT3-based early prophylaxis results in less rejection, permitting less chronic corticosteroid administration.
Antibodies, Monoclonal↗
Dependence of assessment of coronary artery reperfusion during acute myocardial infarction on angiographic criteria and interobserver variability.
The angiographic films of 240 patients with acute myocardial infarction were studied in a randomized trial of intravenous anisoylated plasminogen streptokinase activator complex (APSAC) versus intracoronary streptokinase therapies. The interobserver variability of grading coronary artery perfusion by the Thrombolysis in Myocardial Infarction Study Group (TIMI) criteria was measured as well as the effect of different definitions of reperfusion on the determination of reperfusion rate. There was good agreement in the reading of infarct artery flow grades between 2 blinded observers for each grade considered separately (k = 0.726 +/- 0.014) and for grades 0 or 1 (no perfusion) versus grades 2 or 3 (perfusion) (k = 0.905 +/- 0.011). Discordance between grades 0 or 1 versus 2 or 3 occurred in 74 (5%) of the 1,615 angiographic readings. Discrepancies of clinical significance which affected qualification for study entry, reperfusion or reocclusion status occurred in only 15 patients (6%). Grade 1 flow was found to have the most variable interpretation. Reperfusion rates for APSAC and streptokinase differed significantly when reperfusion was defined by 3 different criteria. The reperfusion rate ranged from 51 to 72% for APSAC and from 60 to 75% for streptokinase depending upon criteria selected. For comparison of the results of different thrombolytic studies, a standard semiquantitative system for grading infarct artery perfusion should be used, readings should be blinded and the criteria used for the definition of reperfusion should be clearly specified.
Aged↗
Effect of reperfusion on electrocardiographic and enzymatic infarct size: results of a randomized multicenter study of intravenous anisoylated plasminogen streptokinase activator complex (APSAC) versus intracoronary streptokinase in acute myocardial infarction.
The effect of early coronary artery reperfusion on ECG and enzymatic parameters was examined in 240 patients with acute myocardial infarction. These patients had participated in a randomized trial comparing intravenous anisoylated plasminogen streptokinase activator complex (APSAC) (n = 123) and intracoronary streptokinase (n = 117) therapy. Reperfusion occurred in 59 of 115 (51%) patients receiving APSAC and 67 of 111 (60%) patients receiving streptokinase (p = NS). There was greater early resolution of ST segment elevation in the reperfused than in the nonreperfused patients (p less than or equal to 0.003) and more rapid Q wave evolution (p less than or equal to 0.03). Sigma Q was lower in reperfused than in nonreperfused patients at 8 hours (1.41 +/- 1.18 versus 2.11 +/- 2.10 mV; p less than or equal to 0.05) and at 24 hours (1.43 +/- 1.25 mV versus 2.08 +/- 1.88 mV; p less than or equal to 0.02). Time to peak level was shorter in the reperfused patients for creatine kinase (CK) (10.7 +/- 5.5 hours versus 14.9 +/- 5.9 hours; p less than 0.0001) and lactic acid dehydrogenase (LDH) (29.6 +/- 13.6 hours versus 34.4 +/- 10.5 hours; less than or equal to 0.03) enzymes. Peak LDH-1 was lower in the reperfused group (274 +/- 149 U/L versus 341 +/- 173 U/L; p less than or equal to 0.04). Reperfusion at a mean of 3.9 hours after the onset of infarction was associated with more rapid resolution of ST segment elevation, faster Q wave evolution, smaller ECG infarct size, earlier cardiac enzyme release, and smaller enzymatic infarct size than later or no reperfusion.
Anistreplase↗
Multicenter reperfusion trial of intravenous anisoylated plasminogen streptokinase activator complex (APSAC) in acute myocardial infarction: controlled comparison with intracoronary streptokinase.
The recent establishment of a firm therapeutic role for reperfusion in acute myocardial infarction has stimulated interest in the development of more ideal thrombolytic agents. Anisoylated plasminogen streptokinase activator complex (APSAC) is a new plasminogen activator possessing properties that are promising for intravenous thrombolytic application in acute myocardial infarction. To assess the reperfusion potential of intravenous APSAC, a multi-center, angiographically controlled reperfusion trial was performed. An approved thrombolytic regimen of intracoronary streptokinase served as a control. Consenting patients with clinical and electrocardiographic signs of acute myocardial infarction were studied angiographically and 240 qualifying patients with documented coronary occlusion (flow grade 0 or 1) were randomized to treatment in less than 6 h of symptom onset (mean 3.4 h, range 0.4 to 6.0) with either intravenous APSAC (30 U in 2 to 4 min) or intracoronary streptokinase (160,000 U over 60 min). Both groups also received heparin for greater than or equal to 24 h. Reperfusion was evaluated angiographically over 90 min and success was defined as advancement of grade 0 or 1 to grade 2 or 3 flow. Rates of reperfusion for the two treatment regimens were 51% (59 of 115) at 90 min after intravenous APSAC and 60% (67 of 111) after 60 min of intracoronary streptokinase (p less than or equal to 0.18). Reperfusion at any time within the 90 min was observed in 55 and 64%, respectively (p less than or equal to 0.16). Time to reperfusion occurred at 43 +/- 23 min after intravenous and 31 +/- 17 min after intracoronary therapy. The success of intravenous therapy was dependent on the time to treatment: 60% of APSAC patients treated within 4 h exhibited reperfusion compared with 33% of those treated after 4 h (p less than or equal to 0.01). Reperfusion rates were also dependent on initial flow grade (p less than or equal to 0.0001): 48% (81 of 168) for grade 0 (APSAC = 43%, streptokinase = 54%), but 78% for grade 1 (APSAC = 78%, streptokinase = 77%). APSAC given as a rapid injection was generally well tolerated, although the median change in blood pressure at 2 to 4 min was greater after APSAC than after streptokinase (-10 versus -5 mm Hg). Mean plasma fibrogen levels fell more at 90 min after the sixfold higher dose of APSAC than after streptokinase (to 32 versus 64% of control). Reported bleeding events were more frequent after APSAC but occurred primarily at the site of catheter insertion and no event was intracranial.(ABSTRACT TRUNCATED AT 400 WORDS)
Adult↗
The economic impact of DRG payment policies on air-evacuated trauma patients.
This study assessed the injury severity, patient outcome, the cost of care, and the economic impact of Medicare DRG payment policies on patients referred to a Level I trauma center. Only 11 of 283 admitted traumatized patients were Medicare patients. Yet, these 11 Medicare patients left the trauma center with a deficit of $249,601. No significant differences were found between the Medicare and non-Medicare groups for Trauma Score, CRAMS Score, Glasgow Coma Score, Injury Severity Score, ICU or hospital length of stay, disability, or mortality. Under DRG's, Medicare payments ($4,237 +/- 2,351/patient) have fallen to 20% of prior cost-based Medicare reimbursements ($21,542 +/- 34,170/patient), are providing only 16% of hospital costs ($26,928 +/- 42,713/patient), and are significantly (p less than 0.0001) less than non-Medicare reimbursements ($15,288 +/- 17,111/patient). Despite the high financial losses occurring when the trauma center treats referred traumatized Medicare patients, when all referred Medicare and non-Medicare patient trauma reimbursements are combined, overall trauma revenues have declined by only 4.3% under DRG's. If Medicare DRG payments were to be adopted by all third-party payers, reimbursement ($5,058 +/- 4,090/patient) would be significantly (p less than 0.0001) less than current hospital reimbursements ($14,801 +/- 16,537/patient) and costs ($16,121 +/- 17,624/patient). These results indicate that although high financial losses result when caring for traumatized Medicare patients, DRG's have not had a major financial effect upon centers receiving referred trauma patients because of the low numbers of admitted traumatized Medicare patients. However, if third-party payers were to enact the Medicare payment system, devastating economic losses would be inflicted upon major trauma centers.
Adult↗
Changes in spontaneous variability of ventricular ectopic activity as a function of time in patients with chronic arrhythmias.
Previous determinations of spontaneous variability in ventricular arrhythmia have often been based on measurements from consecutive days in small patient populations, whereas clinical determinations of drug efficacy typically compare measurements at intervals of 1 week and longer to baseline. We, therefore, sought to determine whether spontaneous arrhythmia variability changes as a function of time during periods ranging from 1 day to 1 year or longer. The percent reduction in the frequency of total premature ventricular complexes (PVCs) and repetitive ventricular beats required to show true drug effect rather than spontaneous variability in PVCs was determined in 47 consecutive patients with chronic ventricular arrhythmias who underwent multiple ambulatory monitor recordings while off active drug treatment (during placebo therapy). The variability in PVC rate was determined during the intervals of 1 day, 1 week, 2 weeks, 3 weeks, 4 weeks, and 1 year or longer. The percent reductions in total PVCs required to exceed the 95% confidence limits of spontaneous variability at these intervals were 55%, 85%, 86%, 93%, 96%, and 96%, respectively. Corresponding values for repetitive beats were 75%, 95%, 92%, 95%, 94%, and 98%, respectively. The percent increase in total PVCs and repetitive beats required to establish "arrhythmia aggravation" caused by an antiarrhythmic drug with a 95% confidence limit also was calculated for this study population and was 124% and 303%, respectively, at 1-day intervals and 2,269% and 4,091%, respectively, at 1-year (or longer) intervals for the 24-hour monitor recordings. Variability was not substantially affected by underlying heart disease or ejection fraction. PVC rate showed a modest negative correlation with variability (r = 0.3). Thus, variability is substantially greater at 1 week, the usual time for clinical assessment of antiarrhythmic drug efficacy, than at 1 day (p less than 0.01). Suppression of more than 85% of total PVCs and more than 95% of repetitive beats appears to be necessary after 1-2 weeks to be confident of a true drug effect. Even greater variability is observed after 1 month and up to 1 year so that reductions of up to 95% in total PVCs and 98% in repetitive beats may represent spontaneous change.(ABSTRACT TRUNCATED AT 400 WORDS)
Anti-Arrhythmia Agents↗
Effect of preoperative hemodynamic support on survival after cardiac transplantation.
The accessibility and success of cardiac transplantation promotes transplantation for a broad range of recipients, including those requiring intravenous inotropes or mechanical-assist devices. To determine if survival is dependent on preoperative requirements for hemodynamic support, we studied 230 patients who underwent transplant at the Loyola, Stanford, and UTAH programs from December 1, 1984 through November 30, 1986, and who were followed up for 34 months postoperatively. Group 1 (n = 132 of 230, 57%) patients required only oral medical therapy to maintain hemodynamic compensation; Group 2 (n = 69 of 230, 30%) patients were dependent on intravenous inotropic support; and Group 3 (n = 29 of 230, 13%) patients required mechanical assistance. Pretransplant characteristics showed that dilated cardiomyopathy was more common in Group 2 patients, and lower cardiac index and ejection fraction were more prevalent in Group 3 patients as expected. Although survival was lower in Group 3 only at 1 month (Group 1, 98.5%; Group 2, 92.8%; and Group 3, 86.2%; p less than 0.01), the survival advantage in Groups 1 and 2 was lost by 3 months, with 1-year survival rates of 88.6% in Group 1, 81.2% in Group 2, and 82.8% in Group 3. Allograft survival and cause of death were not different among the three groups. Acute rejection occurred at a lower monthly frequency in the first 4 months in Group 3 (Group 1, 0.47 +/- 0.03; Group 2, 0.47 +/- 0.05; and Group 3, 0.29 +/- 0.06; p less than 0.01), whereas infectious complications occurred at similar frequencies.(ABSTRACT TRUNCATED AT 250 WORDS)
Assisted Circulation↗
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↗
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↗
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↗